The Natural Thyroid Diet

Thyroid Factor

Thyroid Factor is a program that was created by Dawn Sylvester to help women deal with thyroid issues. Dawn Sylvester is a 57 years old lady that has worked with 1,000's of real women. She has over the time tried to investigate the underlying reason why majority of women lose energy and also struggle with belly fat and fatigue as they age. It is a comprehensive program thatcomprises of Thyro pause, 11 kinds of thyroid saving foods that will work to help you boost fat burning Free T3. The program also teaches you all the hidden causes of thyroid which are making you fat and later a highly reliable Thyroid reboot plan which is an excellent plan you need to tackle your weight. Additionally, there are tips to reduce bulging fat fast and eventually obtain a healthy body. You also get several bonuses all aimed at helping you solve all the problems that comes with being overweight. The three bonuses you get are 21 Day Thyroid weight loss system, 101 Thyroid boosting foods and Thyroid Jumpstart Guide. More here...

Thyroid Factor Summary


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Thyroid and other endocrine disorders

Thyroid disorders can be a diagnostic trap in family practice and early diagnosis is a real challenge. A family practice of 2500 patients can expect one new case of thyroid disorder each year and ten 'cases' in the practice with a slight preponderance of hyperthyroid patients compared with hypothyroid patients. 1 The diagnosis of an overactive or underactive thyroid can be difficult as the early clinical deviations from normality can be subtle. The clinical diagnosis of classical Graves' disease is usually obvious with the features of exophthalmos, hyperkinesis and a large goitre but if the eye and neck signs are absent it can be misdiagnosed as an anxiety state. Elderly patients may present with only cardiovascular signs such as atrial fibrillation and tachycardia or with unexplained weight loss. The hypothyroid patient can be very difficult to diagnose in the early stages, especially if the patient is being seen frequently. Hypothyroidism often has a gradual onset with general...

Endocrine Surgical Procedures Thyroid and Parathyroid Surgery

Thyroid and parathyroid procedures can be considered together as they involve surgery in the same area of the neck, and the haemostatic techniques are generally the same. For convenience, they may be divided into preoperative, intra-operative, and postoperative measures. All patients should stop aspirin, low molecular weight heparin, and similar medication likely to interfere with platelet function, at least one week beforehand. These simple measures will reduce the risk of postoperative ooze into the thyroid bed and prevent haematoma formation within the wound, which may take several weeks to resolve. After resolution of a haematoma, the scar may be tethered and unsightly and may need re-excision to improve the cosmetic appearance. A diamond shaped surgical field is created by mobilising the skin flaps superiorly as far as the thyroid cartilage and inferiorly to the suprasternal notch. It is maintained by a self-retaining Joll's retractor. The approach least likely to cause bleeding...

Plate 79 Parathyroid And Thyroid Glands

The parathyroid glands are usually four in number. Each is surrounded by a capsule and lies on or is partially embedded in the thyroid gland. Connective tissue trabeculae extend from the capsule into the substance of the gland. The thyroid gland is located in the neck in close relation to the upper part of the trachea and the lower part of the larynx. It consists of two lateral lobes that are joined by a narrow isthmus. The follicle, which consists of a single layer of cuboidal or low columnar epithelium surrounding a colloid-filled space, is the functional unit of the thyroid gland. A rich capillary network is present in the connective tissue that separates the follicles. The connective tissue also contains lymphatic capillaries. Figure 2, thyroid gland, human, H& E x200. A histologic section of the thyroid gland is shown here. The follicles (F) vary somewhat in size and shape and appear closely packed. The homogeneous mass in the center of each follicle is the colloid. The...

Medullary thyroid cancer

Expression of carcinoembryonic antigen (CEA) by medullary thyroid carcinoma (MTC), a neoplasm that arises from the parafollicular cells of the thyroid, has been used as a target of radioimmunotherapy. More recently, cancer-testis antigens, in particular NY-ESO-1, have been detected in medullary thyroid cancer (10). Thus, vaccines targeting these antigens may be useful for treatment of this malignancy. Also, because medullary thyroid cancer frequently arises as a familial syndrome, one interesting approach would be to apply immunizations as a way to prevent development of the disease as has been demonstrated in an animal model of familial human MTC (11).

The Importance Of Thyroid Hormone Sulfation During Fetal Development

Type Deiodinaseand Solfate

Thyroid hormone is essential for normal human development, and this is most evident in the central nervous system, where thyroid hormone deficiency in the fetal and neonatal periods can result in severe and prolonged neurodevelopmental deficit. A number of factors are involved in regulating the bioavailability of receptor active thyroid hormone (T3). Of particular importance are the deiodinase and sulfotrans-ferase enzyme systems governing the interconversion (and thus activation or deac-tivation) of the various iodothyronines. Deiodination constitutes one of the principal pathways of thyroid hormone metabolism. Under normal conditions, the prohormone thyroxine (T4) is the predominant secretory product of the thyroid gland. T4 is peripherally converted to receptor active T3 (3,3',5-triiodothyronine) by outer ring deiodination (ORD) or to receptor inactive reverse T3 (rT3) by inner ring deiodination (IRD). Both T3 and rT3 are further deiodinated, and therefore deactivated (via IRD and...

The Importance Of Sulfation In Thyroid Hormone Metabolism

The role of sulfation in thyroid hormone metabolism is intriguing. Sulfated iodo-thyronines do not bind to the thyroid hormone receptors nor are they substrates for D2 and D3, but their deiodination by D1 is strongly augmented. Figure 7.2 shows the effects of sulfation on the deiodination of different iodothyronines by D1 (Visser, 1996b). IRD (inactivation) of T4 sulfate (T4S) and T3 sulfate (T3S) is markedly facilitated, whereas outer ring deiodination (activation) of T4S is blocked (Visser, 1994, 1996b Visser et al., 1988). However, outer ring deiodination of other substrates is not inhibited by sulfation in fact, deiodination of rT3 sulfate (rT3S) is not affected and that of 3,3'-T2 sulfate (T2S) is even greatly stimulated (Visser, 1994 Visser et al., 1988). Under normal conditions, therefore, the main function of sulfation is to induce the irreversible degradation of thyroid hormone.

Thyroid Stimulating Hormone Receptor

The growth and function of the thyroid are controlled by thyrotropin through activation of the thyroid-stimulating hormone (TSH) receptor.36 Mutations in TSH receptors are found in approximately 30 of all human thyroid adenomas.37 In recent years, various constitutively active mutations within the TSH receptor were identified and shown to be associated with continuous stimulation of the cAMP pathway, causing hyperthyroidism and thyroid hyperplasia. Similarly, in Graves' disease, autoantibodies mimic the action of thyrotropin,38 leading to activation of this receptor. Thyroid carcinogenesis, however, is associated with constitutively activating receptor mutants and an activating mutation within the Ras gene, suggesting that both the Ras and TSH mutations act synergistically to cause the tumor phenotype in some differentiated thyroid carcinomas.39

Vitamin D3 and Thyroid Receptors

Thyroid hormone receptors (TRa and TRjS) exhibit multiple modes of DNA binding, including both homodimerization and RXR het-erodimerization on a number of diverse response elements, where they can both activate and silence transcription, depending on the promoter context. The TRs are activated by triiodothyro-nine (T3), and physiological roles for these receptors include regulation of thyroid and pituitary tropic hormone production, affecting a variety of CNS and metabolic functions. Dominant human mutations within the TRfi gene (but not TRa) have been characterized, and individuals carrying these mutations display clinical symptoms of generalized resistance to thyroid hormone.362 The mutations interfere with ligand binding but not dimerization or DNA binding and likely represent dominant negative mutations.

Hypothyroidism and Myxedema Coma

History of the Present Illness Fatigue, cold intolerance, constipation, weight gain or inability to lose weight, muscle weakness thyroid swelling or mass dyspnea on exertion mental slowing, dry hair and skin, deepening of voice carpal tunnel syndrome, amenorrhea. Somnolence, apathy, depression, paresthesias. Past Medical History Hyperthyroidism, thyroid testing, thyroid surgery.

Classification Thyroid Problem

The thyroid-problem is a real world problem. The individual's task is to classify humans thyroid function. The dataset was obtained from the UCI-repository (Blake and Merz, 1998). It contains 3772 training and 3428 testing samples, each measured from one patient. A fitness case consists of a measurement vector containing 15 binary and 6 real valued entries of one human being and the appropriate thyroid function (class). There are three different classes for the function of the thyroid gland, named hyper function, hypo function and normal function. As Gathercole (Gathercole, 1998) already showed, two out of these three classes, the hyper function and the hypo function, are linearly separable. Given the measurement vector as input, an individual of the ACGP system should decide whether the thyroid gland is normal functioning (class 1), or should be characterized as hyper or hypo function (class 2).

Thyroidstimulating hormone free thyroxine triiodothyronine

Thyroid autoantibodies Raised autoantibodies (antimicrosomal or antithyroid peroxidase) are suggestive of Hashimoto's disease (autoimmune thyroiditis). This is the single most cost-effective investigation in the diagnosis of thyroid nodules. It is the best way to assess a nodule for malignancy. Care needs to be taken in the interpretation of the cytology results in conjunction with an experienced cytologist pathologist. Thyroid isotope scan The scan may help in the differential diagnosis of thyroid nodules. A functioning nodule is said to be less likely to be malignant than a nonfunctioning nodule (cyst, colloid nodule, haemorrhage and carcinoma are not functioning). Thyroid ultrasound A thyroid ultrasound is usually more sensitive in the detection of thyroid nodules. A multinodular goitre may be diagnosed on ultrasound while the clinical impression may be that of a solitary nodule (the other nodules not being palpable clinically). A multinodular goitre is said to be less likely to be...

Autoimmune Thyroiditis

Selenium supplementation may improve inflammatory activity in chronic autoimmune thyroiditis patients, as evidenced by a significant reduction in the concentration of thyroid peroxidase antibodies (TPO-Ab) to 63.8 in selenium-supplemented subjects versus 88 (P 0.95) in placebo subjects (Gartner et al 2002). The randomised study of 70 females (mean age 47.5 years) compared 200 jg sodium selenium daily orally for 90 days to placebo. A follow-up crossover study of 47 patients from the initial 70 was conducted for a further 6 months (Gartner & Gasnier 2003). The group that continued to take sodium selenite (200 g day) experienced further significant decreases whereas the group that ceased selenium use experienced a significant increase. The patients who received 200 jg sodium selenite after placebo also experienced a significant decrease in levels of TPO-Ab.

Hyperthyroidism and Thyrotoxicosis

History of the Present Illness Tremor, nervousness, hyperkinesis (restlessness), fever, heat intolerance, palpitations, diaphoresis, irritability, insomnia thyroid enlargement, masses, thyroid pain, amenorrhea. Atrial fibrillation diplopia, reduced visual acuity, eye discomfort or pain, lacrimation recent upper respiratory infection. Previous thyroid function testing. Past Medical History Factors Precipitating Thyroid Storm Infection, surgery, diabetic ketoacidosis, pulmonary embolus, excess hormone medication, cerebral vascular accident, myocardial infarction, labor and delivery, iodine-131 or iodine therapy. Family History Thyroid disease.

Thyroid Hormone Binding Site

FIGURE 6-11 Model of thyroxine-binding prealbumin (TBPA). The schematic model is derived from X-ray crystallographic studies of prealbumin, illustrating the interaction of four identical subunits forming a channel through the interior of the molecule, thereby forming two identical thyroid hormone-binding sites. The channel narrows at the center of the molecule. Although the binding sites are identical, T4 binds cooperatively occupation of T4 at one site presumably alters the conformation of the second site, which results in a lower affinity for the second T4-binding interaction. Depicted on the upper and lower sides of the molecule is a symmetric 3-pleated sheet structure that is relatively rich in amino acids with ionic side chains and that also contains tryptophan molecules. On the basic of computer graphic modeling studies, this site has been proposed to be a DNA-binding site. Reproduced with permission from Eberhardt, N. L., Apriletti, J. W., and Baxter, J. D. (1980). The...


Considering that this condition is associated with reduced body stores of carnitine and that l-carnitine is a peripheral antagonist of thyroid hormone action in some tissues according to in vivo studies, carnitine treatment has been investigated in hyperthyroidism. One 6-month, randomised, double-blind placebo-controlled trial involving 50 women with induced suppression of thyroid-stimulating hormone showed that doses 2007 Elsevier Australia


Myxedema coma results from extreme hypothyroidism and is characterized by impaired mentation, hypoventilation, hypothermia, hyponatremia, and CHF. Treatment is with iV thyroid hormones (300-500 mcg of levothyroxine sodium in patients without heart disease). Cortisol should also be given.

Thyroid Hormone

Spontaneous and stimulated GH secretion is markedly attenuated in clinical and biochemical hypothyroidism in humans this abnormality corrects during thyroid hormone replacement (7,57,58). Thyroid hormone deficiency is associated with reduced hypothalamic GHRH production, leading to GH deficiency and down-regulation of GHRH receptor numbers on pituitary somatotropes (7,59). Thyroid hormone facilitates binding of GHRH to its receptor. GH secretion is reduced in hypothyroid subjects following Hyperthyroid subjects have significant increases in 24-h GH pulse frequency, augmented GH pulse amplitude, and 3.7-fold higher GH production rates, similar to the effects of sex steroids on GH secretion (63). These observations of enhanced GH secretion in hyperthyroidism suggest some alteration in GH neuroregulatory control including increased somatotrope responsiveness to GHRH or a reduction in somatostatin tone, and is independent of IGF concentration (63). On the other hand, other investigators...

Thyroid gland

The thyroid gland is located in the anterior neck region adjacent to the larynx and trachea The thyroid gland is a bilobate endocrine gland located in the anterior neck region and consists of two large lateral lobes connected by an isthmus, a thin band of thyroid tissue. The two lobes, each 5 cm in length, 2.5 cm in width, and 20 to 30 g in weight, lie on either side of the larynx and upper trachea. The isthmus crosses anterior to the upper part of the trachea. A pyramidal lobe often extends upward from the isthmus. A thin connective tissue capsule surrounds the gland. It sends trabeculae into the parenchyma that partially outline irregular lobes and lobules. Secretory follicles constitute the functional units of the gland. The thyroid gland develops from the endodermal lining of the floor of the primitive pharynx The thyroid gland begins to develop during the fourth week of gestation from a primordium originating as an endodermal thickening of the floor of the primitive pharynx. The...

Parathyroid glands

The parathyroid glands are small endocrine glands closely associated with the thyroid. They are ovoid, a few millimeters in diameter, and arranged in two pairs, constituting the superior and inferior parathyroid glands. They are usually located in the connective tissue on the posterior surface of the lateral lobes of the thyroid gland. However, the number and location may vary. In 2 to 10 of individuals, additional glands are associated with the thymus. Structurally, each parathyroid gland is surrounded by a thin connective tissue capsule that separates it from the thyroid. Septa extend from the capsule into the gland to divide it into poorly defined lobules and to separate the densely packed cords of cells. The connective tissue is more evident in the adult, with the development of fat cells that increase with age and ultimately constitute as much as 60 to 70 of the glandular mass. The glands receive their blood supply from the inferior thyroid arteries or from anastomoses between...

Ithyroid Follicles

Thyroid follicles are hounded by follicular cells and parafollicular cells. A. Contain thyroid-stimulating hormone (TSH) receptors E. Oxidize iodide (2I + H207 > I7) using the enzyme thyroid peroxidase and iodinate tyrosine residues in thyroglobulin, thereby forming monoiodotyrosine (MIT) and di-iodotyrosine (DIT), which are then coupled to form triiodothyronine (T5) and thyroxine (T4) H. Deiodinatc MIT and DIT using the enzyme deiodinase to recycle iodide (I ) and secrete Tj and T.( into the bloodstream, which then circulate bound to thyroid-binding globulin (TBG). T4, which is converted by the liver and kidney into the functionally more potent T5, accounts for 90 of the thyroid output T, accounts for 10 of the thyroid output.

Thyroid Tumors

Thyroid tumors are the second tumor type for which the U.S. EPA has developed generic guidance for risk assessment (55). The agency efforts have been directed specifically at tumors of the thyroid follicular cells, but some of the information gained from analysis of these tumors will likely be applicable to other endocrine tumor sites in the future. Clinical manifestation of thyroid cancer in humans in the United States is uncommon and largely nonfatal. The only known human thyroid carcinogen is X-radiation, which causes an increase in papillary tumors. Human thyroid follicular cell cancer is most often diagnosed histologically as a papillary tumor. The rodent thyroid neoplasms rarely metastasize, whereas the human cancers frequently metastasize. The molecular events that lead to thyroid follicular cell tumors are not fully known. In rodents, these tumors arise from mutation, perturbation of thyroid and pituitary hormone status with increased stimulation of thyroid cell growth by...

Tissue Distribution Of The Human Sult1a Subfamily

One interesting observation made by Richard et al. (2001) was the developmental expression difference apparent between SULT1A1 and SULT1A3 in lung and liver tissues. Assessing the dopamine and thyroid hormone sulfonation ability of fetal tissues, it was found that high liver SULT1A1 activity was generally retained into adulthood however, lung activity reduced approximately 10-fold toward 3,3'-T2 (Gilissen et al., 1994 Richard et al., 2001). Sulfonation activity of dopamine was high in the fetal liver and lung but reduced significantly in the postnatal tissues (Pacifici et al., 1993 Richard et al., 2001). Protein levels confirmed these results, suggesting that SULT1A1 and 1A3 are abundantly expressed in the fetal liver and that the SULT 1 A3 enzyme almost disappears in the adult tissue (Richard et al., 2001). This same pattern has also been observed for SULT1A3 in the kidney (Cap-piello et al., 1991). These data suggest an important role for these two SULTs in

Ontogeny And Tissue Distribution Of Iodothyronine Sulfotransferases

HSULT1E1 is expressed in the liver, mammary gland, uterus, placenta, and in a wide range of fetal tissues, such as lung, liver, adrenal, kidney, small bowel, thyroid, heart, and brain (Rubin et al., 1999 Stanley, 2001 Stanley et al., 2001 Strott, 1996). It is possible that the hSULT1E1 in the endometrium contributes to the high iodo-thyronine sulfate levels in the fetal serum and amniotic fluid (see Discussion).


SULT1B1 was initially referred to as a thyroid hormone-sulfating SULT due to its ability to sulfate a number of thyroid hormones, including T3 and T4 (Fujita et al., 1997 Wang et al., 1998). The highest levels of activity were observed with 3,3'-T2, which is consistent with the role of sulfation in increasing the rate of thyroid hormone deiodination (Visser, 1994, 1996). Thyroid hormones are also substrates for several other human SULTs. SULT1E1 efficiently sulfates thyroid hormones, and SULT1A1 has thyroid hormone sulfation activity as well (Kester et al., 1999a, b Young et al., 1988). Expressed SULT1B1 also efficiently conjugates several prototypical phenolic substrates such as 1-naphthol and PNP. Most steroids are not readily sulfated by expressed human SULT1B1 (Fujita et al., 1999 Wang et al., 1998).

Sult1 Family

SULT1B1 thyroid hormones, 2-naphthol, dopamine The SULT1B subfamily has been identified recently and may be involved in the sulfation of thyroid hormones (Fujita et al., 1997, 1999 Saeki et al., 1998 Sakakibara et al., 1995 Tamura et al., 1999 Wang et al., 1998). This family also catalyzes the sulfation of prototypic phenolic substrates, such as 2-naphthol and dopamine, but not steroid hormones. (HUMAN)SULT1B1 mRNA has been detected in liver, colon, small intestine, and blood leukocytes. The SULT1C subfamily is also a recently identified gene family that encodes at least four isoforms (Hehonah et al., 1999 Her et al., 1997 Nagata et al., 1993 Sakakibara et al., 1998a Tamura et al., 1998 Xiangrong et al., 2000 Yoshinari et al., 1998b). The function of these enzymes is not yet fully understood but (RAT)SULT1C1 and (HUMAN)SULT1C4 catalyze the sulfation of the procarcinogen N-OH-2-acety-laminoflorene as well as p-nitrophenol, the prototypic phenolic SULT substrate. (RAT)SULT1C1 is liver...


Paps And Sulfation

Thyroid hormone metabolism is an important process in the regulation of thyroid hormone homeostasis. The prohormone T4 can be activated by outer ring deiodina-tion to T3 or inactivated by IRD to rT3. T3 and rT3 are further metabolized to 3,3'-T2. In addition, iodothyronines are also metabolized by sulfotransferase-catalyzed conjugation of the phenolic hydroxyl group (Visser, 1996b). Still, the tissue-specific expression of the sulfotransferases makes the understanding of the physiological importance of the different sulfotransferases rather complex. We showed a strong correlation between substrate specificities of hSULTlAl and those of native iodothyronine sulfotransferase activities in human liver and kidney, which suggests an important role for hSULTlAl in thyroid hormone sulfation in these tissues (Figure 7.5 Kester et al., 1999a). Richard et al. (2001) studied hSULTlAl and hSULT1A3 expression and 3,3'-T2 sulfation in the hSULT1E1 may be especially important for iodothyronine...


Until recently, SULT1A1 was predominantly seen as an enzyme that was primarily involved in xenobiotic metabolism. This observation was based on it having the widest tissue distribution of any SULT, including liver and intestine, and its broad substrate range (Eisenhofer et al., 1999 Falany, 1997). The recent elucidation of the crystal structure of SULT1A1, which shows the active site of this enzyme to be more versatile than first expected, provides a rational explanation for its substrate diversity. More recent data suggest that SULT1A1 plays a significant role in the metabolism of the iodothyronines, especially 3,3'-T2 (Li et al., 2001 Richard et al., 2001), which we have recently shown binds effectively to the active site of this isozyme (Gamage et al., 2003). 3,3'-T2 is thought to act through nonnuclear pathways to enhance mitochondrial respiration and thus resting metabolism (Li et al., 2001). SULT1A1 is also capable of sulfonating T3 and thyroxine (T4) and may play a more...

Sult1c1 And Sult1c2

In a human fetal liver-spleen cDNA library. The clone was obtained from the American Type Culture Collection and encoded a 296 amino acid protein that was 62 identical in sequence to a rat SULT1C1 sequence (Nagata et al., 1993). SULT1C1 displays approximately 50 amino acid sequence identity with the human SULT1 proteins, resulting in its inclusion in the SULT1 subfamily. SULT1C1 message expression was reported in human adult stomach, kidney, and thyroid as well as in fetal kidney and liver (Her et al., 1997). The structural SULT1C1 gene was localized to chromosome 2q11.1-11.2 (Her et al., 1997). Resequencing of the SULT1C1 gene of 89 Caucasians detected 4 nonsynonymous SNPs and 5 insertion deletions, indicating that SULT1C1 is polymorphic in humans (Freimuth et al., 2001).


As with SULT2A1, reports on the expression of the SULT2B1 isoforms in human tissues vary considerably depending on the reporting laboratory and the methodology employed. Northern analysis performed using a probe that would detect both SULT2B1 isoforms revealed strong expression in the placenta, prostate, and trachea with faint expression in the small intestine and lung, whereas there was no expression in the heart, brain, spinal cord, liver, skeletal muscle, kidney, pancreas, ovary, testis, stomach, colon, adrenal, thyroid, and bone marrow (Her et al., 1998). RT-PCR revealed that SULT2B1a is expressed in the colon, kidney, ovary, and skin in addition to those tissues detected by northern analysis (Javitt et al., 2001). RT-PCR further revealed that the SULT2B1b isoform is more widely and vigorously expressed than SULT2B1a (Javitt et al., 2001). Another RT-PCR analysis of adult human tissues revealed SULT2B1a and SULT2B1b expression in skin, esophagus, stomach, duodenum, colon, lung,...


SULT1C2 (originally referred to as SULT1C1) was identified on the basis of sequence homology of its cDNA to those of other SULTs (Her et al., 1997). In adults, this enzyme is most highly expressed in the stomach, thyroid, and kidney, and it is also expressed in the fetal liver (Her et al., 1997). Cloning and characterization of the human SULT1C2 gene (Freimuth et al., 2000) made it possible to perform a genotype-to-phenotype resequencing study of this gene. That experiment utilized DNA extracted from blood samples obtained from 89 randomly selected Caucasian blood donors (Freimuth et al., 2001) and resulted in the identification of 19 polymorphisms, including 4 nonsynonymous cSNPs and 5 insertions deletions

Evolution of the Nuclear Receptor Superfamily

Detailed comparative sequence analysis of receptors across species predicts that the DNA-binding function of these proteins evolved prior to ligand-binding capacity. All NRs from organisms that evolved prior to chordates, arthropods, and nematodes are more similar to orphan receptors that lack known ligands than to steroid or thyroid family members, suggesting that the prototypes of NRs were orphans.9,13,14 Steroid hormone receptors are apparently restricted to vertebrates, with the exception of the insect ecdysone receptor (EcR), representing the prototypical steroid receptor. The insect EcR, which most closely resembles the farnesoid X receptor (FXR) in primary sequence, is required for virtually every aspect of insect larval meta-morphosis.15 The primary function of EcR in this process is to induce expression of numerous orphan NRs (several of which have vertebrate homologs of unknown function) and establish a temporal regulatory hierarchy of NR activity.16 Interestingly, EcR...

Only LAmino Acids Occur in Proteins

With the sole exception of glycine, the a-carbon of amino acids is chiral. Although some protein amino acids are dextrorotatory and some levorotatory, all share the absolute configuration of L-glyceraldehyde and thus are L-a-amino acids. Several free L-a-amino acids fulfill important roles in metabolic processes. Examples include ornithine, citrulline, and argininosuccinate that participate in urea synthesis tyrosine in formation of thyroid hormones and glutamate in neurotransmitter biosynthesis. D-Amino acids that occur naturally include free D-serine and D-aspartate in brain tissue, D-alanine and D-glutamate in the cell walls of grampositive bacteria, and D-amino acids in some nonmam-malian peptides and certain antibiotics.

Resection Specimens

Total laryngectomy is the operation of choice in cases of radiotherapy failure, bulky T3 and T4 lesions, subglottic tumours and cord immobility and post-radiation perichondritis (crippled larynx). The ipsilateral lobe of thyroid is included when there is a likelihood of extralaryngeal spread in the subglottic region. The larynx will be included in major resections of hypopharynx.

Extent Of Local Tumour Spread

Thyroid nodule 8 to 10 blocks including the capsule to distinguish fol-licular adenoma from minimally invasive follicular carcinoma. Ovarian tumours 1 block centimetre diameter to account for the spectrum of benign, borderline and malignant changes in one lesion, particularly mucinous tumours. pM requires microscopic examination of distant metastases which is often not available to the pathologist and therefore designated on clinical or radiological grounds. If available (e.g. a multidisciplinary meeting), the TNM categories can be stratified into clinical stage groupings which are used to select and evaluate therapy, e.g. carcinoma in situ is stage 0 while distant metastases is stage IV. However, for the most part the pathologist concentrates on pT and pN which gives reasonably precise data to estimate prognosis and calculate end results. Stage grouping is mostly based on the anatomical extent of disease, but for some tumour sites or entities other factors are included histological...

Clinical Presentation

Lesions in the neck usually present as swellings and may be associated with any of the major anatomical structures in the region, in particular lymph nodes, thyroid gland and salivary glands or from other tissues such as skin, blood or lymphatic vessels, nerves or fat. Disease affecting lymph nodes usually presents as enlargement, either a single lymph node or several nodes, unilaterally or bilaterally. The nodes may be tender or painless and vary in consistency from soft to firm, rubbery or hard. In young patients cervical lymphadenopathy is usually due to a reactive process but a neoplasm is more likely in older patients. Malignant lymphoma commonly presents as cervical lymphadenopathy metastatic deposits in cervical lymph nodes may be the presenting feature of tumours in the posterior tongue, nasopharynx, tonsil, larynx or thyroid gland. Metastases in cervical lymph nodes usually derive from primary lesions above the level of the clavicles although 10 will arise from distant sites,...

Clinical Investigations

Swellings in the neck require thorough clinical evaluation to determine the tissue or organ affected, whether the enlargement is solid or cystic and whether or not adjacent tissues are involved. Movement on swallowing tends to point to an intimate relationship with the hyoid bone or thyroid gland while pulsation or the detection of a bruit indicates association with or origin from major vascular structures. Tumours may involve adjacent nerves producing characteristic patterns of paralysis or altered sensation, such as Horner's syndrome or Trotter's syndrome. Ultrasound investigation is helpful in identification of cystic lesions and can provide information on the presence of other lesions in adjacent organs without the risks of ionising radiation. Plain radiographs of the facial bones or sinuses may reveal clinically undetected lesions while barium studies are useful in visualising pharyngeal diverticula or in tracking developmental sinuses or fistulae. CT scanning and MR imaging can...

Gross Description

Bilateral pleural effusions were noted with adhesions more prominent on the right side. The parenchyma had a red, congested appearance, but no discrete lesions were noted. The liver weighed 1920 g and had a dark red cut surface. The kidneys weighed 280 g combined and exhibited multiple cortical scars in keeping with remote renal infarctions. The spleen weighed 280 g. The thyroid weighed 25 g and had a multinodular appearance.

The Platelet Derived Growth Factor Receptor Beta Translocations

The t(5 i2)(q33 pi2) is observed in i of patients with chronic myelomonocytic leukemia (CMML). In i994, the molecular consequences of this translocation were elucidated. The gene encoding the beta chain of the platelet derived growth factor receptor (PDGFRB) is involved on chromosome 5. A novel ETS-like (Erythroblastosis Virus Transforming Sequence) transcription factor, TEL (translocated ETS in leukemia, also known as ETV6), is the gene affected on chromosome i2. The translocation creates a fusion gene and the encoded fusion protein contains the 5' portion of TEL and the 3' portion of PDGFRB (Golub et al. i994). Biochemical studies have revealed that the PDGFRB kinase activity is perturbed and contributes to the transformed pheno-type. TEL encodes a transcriptional repressor, and is promiscuously involved in translocations with some 4o genes in hematologic malignancies (Rowley 2ooo). Interest has increased in identifying this translocation, which predicts for a response to imatinib...

Clinical Aspects

Thyroid hormone deficiency may result in a wide variety of clinical and physiological disturbances in virtually every organ system. The classic disease state is myxedema the accumulation of mucinous edema results in facial periorbital and peripheral edema involving both the hands and feet. The periorbital edema contributes to the patient's haggard appearance and includes a droop of the upper eyelid. Table 6-6 lists the major causes of hypothyroidism. Hashimoto's disease is an autoimmune thyroid disease in which the subject has circulating thyroid antibodies. It is not known whether these antibodies functionally contribute to the state of hypothyroidism. The typical Human growth hormone* TSHa*, TSH 3* (thyroid-stimulating hormones) EGF receptor* Myosin heavy chain 3 In most cases, the effects of T3 + the thyroid receptor were assessed by determinations of steady-state mRNA levels. For those genes with an asterisk (*), the presence of an HRE or hormone response element has been...

Krzisnik Krk Longevity

Gussekloo, J., van Exel, E., de Craen, A.J., Meinders, A.E., Frolich, M., and Westendorp, R.G. (2005). Thyroid status, performance, and survival in old age. JAMA 292, 2591-2599. Hauck, S.J., Hunter, W.S., Danilovich, N., Kopchick, J.J., and Bartke, A. (2001). Reduced levels of thyroid hormones, insulin, and glucose, and lower body core temperature in the growth hormone receptor binding protein knockout mouse. Exp. Biol. Med. 226, 552-558. Ooka, H., Fujita, S., and Yoshimoto, E. (1983). Pituitary-thyroid activity and longevity in neonatally thyroxine-treated rats. Mech. Ageing Dev. 22, 113-120.

B TAFContaining Complexes

Human Mediator, first purified from HeLa cells as a protein complex that associates with the thyroid hormone receptor a (TR a) in a ligand-dependent manner, was able to potentiate TRa-mediated transcription in vitro (Fondell et al., 1996). This TR-associated protein complex (TRAP) contains many protein subunits subsequently found also present in other coactivator complexes, such as SRB MED-containing cofactor complex (SMCC Ito et al., 1999), vitamin D receptor-interacting protein complex (DRIP Rachez et al., 1998), activator-recruited complex (ARC Naar et al., 1999), positive cofactor 2 (PC2 Malik et al., 2000), cofactor required for Spl activation (CRSP Ryu et al., 1999), and negative regulator of activated transcription (NAT Sun et al., 1998). In humans, at least two forms of Mediator complexes, Mediator-P.5 and Mediator-P.85 isolated individually from 0.5 M and 0.85 M KC1 fractions of the Pll phosphocellulose ion-exchange column, have been identified and demonstrated to enhance...

Metabolism Energy Expenditure

Adults with long-standing GH-deficiency have reduced whole body resting energy expenditure (REE), with lower values than predicted for age, sex, height, and weight (46). GH replacement in GH-deficiency results in rapid and large increases in REE (10,47,48). Because REE is largely dependant on LBM metabolic activity, much of this increase is attributable to the observed increase in LBM associated with GH replacement. However, when changes in REE are expressed per LBM these rises are still significant, indicating that direct increases in cellular metabolism are responsible for some of the increased REE (10). GH treatment of the GH-deficient adult results in an increase in circulating tri-iodothyronine (T3) levels, both in patients on thyroxine replacement and those with normal thyroid function (49), indicating that GH is a physiological regulator of thyroid function, in particular the peripheral conversion of thyroxine (T4) to T3. This effect on T4 metabolism probably accounts for some...

Activation of Protein Kinases in Human Cancer

Chromosomal translocations can activate protooncogenes, either by linking the protooncogene to a more powerful or inappropriately regulated promoter or by generating a gene fusion linking the protooncogene product to a heterologous protein. In the latter case, activation can occur either by deletion of an autoinhibitory domain or because the fusion partner provides an activating function, such as dimerization or localization to a novel intracellular compartment. Fusions of receptor or non-receptor tyrosine kinases to heterologous proteins are observed in a variety of cancers and leukemias. Examples include the Tel-PDGFRP fusion in chronic myelomonocytic leukemia 41 , the ZNF198-FGFR1 fusion in certain forms of acute myelogenous leukemia 42 , and a variety of fusions involving TrkA, Met, or Ret in papillary thyroid carcinomas 43 (for a complete listing, see Table 1 in Blume-Jensen and Hunter 6 ).

Mechanical Methods Sutures and ties

Suturing can be a valuable adjunct for haemostasis of the thyroid remnant after subtotal resection of the thyroid, for fixing the capsule of the gland to the pretracheal fascia. Similarly, absorbable sutures can be used for controlling troublesome bleeding from damaged anterior jugular veins. Absorbable sutures are recommended rather than silk, as adverse reactions have been reported with the latter.4 Surgicel (Johnson & Johnson, Somerville, New Jersey, USA) is a resorbable oxidised cellulose material that can be placed into the thyroid wound before closure. It comes prepared as a sterile fabric meshwork that becomes fully absorbed with blood, swelling to a brown gelatinous mass that aids in clotting. Its mechanism of action

Haemostatic Agents Fibrin sealant

Fibrin sealants have not been studied well in thyroid surgery,24-26 but have been widely used in many areas of surgery to obtain haemostasis. They are easy to handle, rapidly absorbed, and have a haemostatic action independent of the general clotting mechanism. They appear to have similar complication rates compared to conventional techniques and lead to lower drainage output after thyroidectomy.26

Interaction with Corepressors

Ski was first identified as a viral oncogene (v-Ski) from the Sloan-Kettering avian retrovirus that transforms chicken embryonic fibroblasts (Liu et al., 2001b Luo, 2004). SnoN is a member of the Ski proto-oncogene family. In addition to being an oncogene, SnoN appears to act as a tumor suppressor, at least in certain cells (Liu et al., 2001b Luo, 2004). Ski and SnoN directly binds to the N-CoR and mSin3A that form a complex with HDAC (Luo et al., 1999 Nomura et al., 1999). In addition, Ski has been shown to be able to bind directly to the corepressors HIPK2 and MeCP2 (Kokura et al., 2001 Harada et al., 2003). Ski is also required for transcriptional repression by several other proteins, including the Mad, the thyroid hormone receptor-P, Rb protein and the Gli3 repressor (Liu et al., 2001b Luo, 2004). Thus, Ski appears to be an integral part of the transcriptional repression machinery.

Prolactin And Tsh Effects

A double-blind, placebo-controlled study involving 20 subjects with depression identified a significant reduction in prolactin concentrations after 14 days' treatment with SAMe (Thomas et al 1987). The results of a study conducted in 1990, however, suggest that the effects on these hormones may be gender specific, with women demonstrating an augmented response of thyroid stimulating hormone (TSH) and no effect on prolactin levels, whereas release of both TSH and prolactin was inhibited in male subjects (Fava et al 1990). If SAMe does exert dopaminergic effects, as presently suspected, then it should also be taken into consideration that dopamine naturally inhibits both TSH and prolactin secretion in humans.

Alteration of Estrogen Receptor Interaction with Coregulator Proteins

The corepressors silencing mediator of retinoid and thyroid receptors (SMRT) and nuclear receptor-corepressor (N-CoR) bind to ER in the absence of ligand and silence transcription. Unlike coactivators that have intrinsic his-tone acetylase activity, one of the functions of corepressors is to recruit a complex of proteins having histone deacetylase activity, to repress gene expression by maintaining chromatin in a more condensed state.37,99 The inhibitory potency of antiestrogens is enhanced by recruitment of other coregulators, including an ER-selective repressor of ER activity in addition to SMRT and N-CoR.102-104 Corepressor expression is reduced in some tamoxifen-resistant breast cancers.104

PolyQ Diseases as Transcriptionopathies

AR androgen receptor, CA150 coactivator 150, CBP cyclic AMP response element binding protein, CtBP C-terminal binding protein, Crx cone-rod homeobox containing gene, htt huntingtin, HYP-B htt-yeast partner, mSin3a mammalian Sin3 protein-A, MTG8 myeloid translocation gene on 8q22, NCoR nuclear receptor corepressor NF-kB nuclear factor-KB, P CAF p300 CBP-associated factor, REST NRSF repressor element-1 transcription factor neuron restrictive silencer factor, SMRT silencing mediator of retinoid and thyroid hormone receptors, Spl specificity protein-1, TAF4 TBP-associated factor 4, TAF10 TBP-associated factor 10

Androgen Receptor Structure And Function

The AR is a member of the superfamily of nuclear transcription factors, which consists of more than 300 members across vertebrates, arthropods, and nematodes and includes receptors for steroid hormones, vitamin D, retinoic acids, and thyroid hormones, as well as a number of orphan receptors for which no ligand has yet been identified.1 Specifically, the AR is a member of the class III NR family, including receptors for estrogen (ER), progestin, glucocorticoids (GR), mineralocorticoids (MR), and the orphan estrogen-related receptors, which represent the terminal derivatives of cholesterol biosynthesis.3 Like many other NRs e.g., GRs, progesterone receptors (PRs), and ERs , the AR contains a ligand-dependent activation function (AF-2) in helix 12 of the ligand-binding domain (LBD), which interacts predominantly with LxxLL motifs of the p160 coactivators. A key functional role for AF-2 is to recruit, in a ligand-dependent manner, chromatin-remodeling factors, which may bridge or...

Hormone Receptors Are Of Central Importance

All receptors have at least two functional domains. A recognition domain binds the hormone ligand and a second region generates a signal that couples hormone recognition to some intracellular function. Coupling (signal transduction) occurs in two general ways. Polypeptide and protein hormones and the cate-cholamines bind to receptors located in the plasma membrane and thereby generate a signal that regulates various intracellular functions, often by changing the activity of an enzyme. In contrast, steroid, retinoid, and thyroid hormones interact with intracellular receptors, and it is this ligand-receptor complex that directly provides the signal, generally to specific genes whose rate of transcription is thereby affected. The domains responsible for hormone recognition and signal generation have been identified in the protein polypeptide and catecholamine hormone receptors. Steroid, thyroid, and retinoid hormone receptors have several functional domains one site binds the hormone...

There Is Variation In The Storage Secretion Of Hormones

A several-week supply of T3 and T4 exists in the thy-roglobulin that is stored in colloid in the lumen of the thyroid follicles. These hormones can be released upon stimulation by TSH. This is the most exaggerated example of a prohormone, as a molecule containing approximately 5000 amino acids must be first synthesized, then degraded, to supply a few molecules of the active hormones T4 and T3.

Deficiency Signs And Symptoms

Secondary deficiencies can develop in chronic diarrhoea, liver disease, chronic alcoholism, adrenal or thyroid hormone insufficiency and postoperative situations in which TPN solutions lack riboflavin. In most cases, riboflavin deficiency is accompanied by other vitamin deficiencies such as vitamin B6, niacin and folic acid. Drugs that impair riboflavin absorption or utilisation by inhibiting the conversion of the vitamin to the active coenzymes include tricyclic, antidepressants, chemotherapy drugs and psychotropic agents. There is also evidence suggesting an apparent increase in riboflavin requirements with increased physical exercise.

Akt signalling in cancer growth and invasion

The induction of apoptosis by staurosporine as well as by etoposide, both well-established mitochondrial apoptotic stimuli, is accompanied by marked activation of Akt prior to the onset of apoptosis, and the resultant overexpression of Akt indeed greatly delays apoptosis (Tang et. al., 2001). It is to be expected that deregulation of the restraint on apoptosis would lead to tumour expansion and this has turned out to be the case. Akt is over-expressed in cancers of the thyroid (Ringel et al., 2001). Akt is said to be constitutively active in non-small cell lung carcinoma cells lines (Brognard etal., 2001). Its activation occurs upon exposure of breast cancer cell lines to oestrogen, irrespective of their ER status (Tsai et al., 2001). Zinda et al. (2001) found no differences in Akt RNA expression of normal and tumour tissues derived from lung, breast, prostate and colon. However, one ought to take cognisance of the possibility that there might yet be differences in protein expression...

Neoplastic Conditions

Metastatic carcinoma this is by far the most common malignant tumour in bone and presents as bone pain or pathological fracture. The most common primary sites are lung, kidney, breast, prostate and thyroid. Most metastatic tumours produce lytic lesions but prostatic secondaries are often sclerotic. The usual skeletal sites are proximal long bones, rib, pelvis and vertebrae. Metastatic disease is distinctly uncommon in the skeleton distal to the elbow or knee.

Inhibitors of Type2 Serine Threonine Phosphatases

Sequence, first identified in the transcription factor NFAT (nuclear factor of activated T cells), a PP2B substrate. These include CAIN, MCIP, and the product of the disease gene associated with Down's syndrome, the thyroid hormone-inducible protein ZAKI-4. Over-expression of these proteins suppresses PP2B functions consistent with their actions as PP2B inhibitors. PP2B also binds to immunophilins that in turn bind the immunosuppressive drugs cyclosporin and FK506 to inhibit calcineurin activity. Experimental evidence suggests that some immunophilins bind PP2B in the absence of drugs and may regulate its phosphatase activity.

On The Physiological Role Of Igfi And Igfii

The IGF molecules appear to regulate cell proliferation in both epithelial and mesenchymal tissues. They act as a non-tissue-specific permissive mitogen, required for optimal proliferative responses to highly tissue-specific trophic factors such as platelet-derived growth factor (PDGF), fibroblast growth factor (FGF) or thyroid-stimulating hormone (TSH). They consequently perform the function of a general progression factor for cells previously stimulated by a more specific competent factor (81). This has been formally demonstrated using cells derived from mice with a targeted disruption of the IGF-1R genes (IGF-lR . These cells do not grow in serumfree medium supplemented with growth factors that sustain the same type of cells derived from wild type littermates (82).

Potential Adverse Experiences

The definition of appropriate treatment populations depends in part upon the balance of specific benefits and risks. A preliminary report indicates that a low plasma level of IGF-1 may correlate with increased mortality in patients over 70 yr old (52), suggesting a potential benefit in treatments which elevate IGF-1. However, just as thyroid hormone replacement can worsen the prognosis of patients with low-T3 syndrome, a recent study of high-dose GH treatment in critical illness, a state of GH resistance, showed a worse outcome in the GH treatment group (53). This is a somewhat different situation from the reduced GH secretion seen in aging, but it raises caution about the potential risks in reversing changes that may be in part adaptive.

Mechanism of transduction of signals by

Can one formulate a putative mechanism by which Akt might activate specific transcription factors that might be associated with specific cellular properties characterising the development of cancer At least three isoforms of Akt have been identified. There seems to be no differential expression between the Akt 1, 2 and 3, and it is uncertain if they are differentially expressed between normal and neoplastic tissues. Whilst Ringel et cil. (2001) found them over-expressed in thyroid carcinomas as compared with corresponding normal tissue, Zinda et al. (2001) encountered no significant differences in their investigations, which included normal and cancers of the colon, lung, breast and the prostate. It should be noted however that EGF might activate a specific isoform of Akt (Okano et al., 2001).

Cowdens Syndrome Definition

Cowden syndrome (CS), also known as multiple hamartoma syndrome or Cowden disease, was first described by Lloyd and Dennis in 1963 (1) as a multisystem disorder with characteristic mucocutaneous lesions and abnormalities of the breast, thyroid, and gastrointestinal tract. They named the disorder after their first patient, Rachel Cowden, who died due to breast cancer. CS is a rare genetic disorder with an autosomal-dominant pattern of inheritance and variable expressivity. Characteristic lesions present in nearly all patients with CS include trichilemmomas on the face, acral keratoses on the hands, and oral papillomas of the mouth. Benign and malignant neoplasms of the breast and thyroid occur in up to two-thirds of patients. Intestinal tract hamartomatous polyps are seen in more than one-half of patients (2).

Gelatin Sponge with Thrombin

Observed within a week, producing a definite encapsulation of the sponge. Subsequently, this encapsulation became fibrous. Sinclair and Douglas41 in 1944 found that the local implantation of gelatin into wounds led to accelerated fibroplasia and increased strength. The gelatin sponge was used in 15 clinical cases in various ways to determine its behaviour in human tissues. It has been used in the incisions in the liver to obtain specimens for liver biopsy, on the undersurface of the liver after cholecystectomy, on thyroid beds after thyroidectomy, on dermatome donor areas, in laparotomy wounds, and on the surface of granulating wounds. According to the authors, however, the observations were too limited to draw conclusions other than that bleeding was controlled and there were no complications that might be attributed to the gelatin sponge. Jampolis et al.42 and Jenkins et al.43 in 1947, conducted a series of 15 experiments on dogs and found it possible to control haemorrhage from...

Chromosomal translocation in synovial sarcomas

A translocation t(X 18) (pll.2 qll.2) occurs consistently in synovial sarcomas. Several genes are located at the breakpoints in this translocation. They are SYT occurring on chromosome 18, and members of the testis cancer antigen SSX gene family, namely SSX1, SSX2 and SSX4 on the X-chromosome. The SSX genes are normally expressed in the testis and the thyroid. Of the SSX homologues, SSX J, SSX2 and SSX4 are frequently expressed in human neoplasms. SSX3 is not usually detected. Furthermore, SSX expression is found in many forms of cancer including breast cancer, colorectal cancer, head and neck tumours, melanoma and in lymphomas. No expression of the SSX genes is detectable in leukaemias, thyroid cancers, and seminomas (Tureci et al., 1998).

Radioactive Isotopes Reveal Physiology

Photos Medical Radioactive Isotopes

Vicki's thyroid gland had been removed three months earlier, and this test was to determine whether any active thyroid tissue remained. The thyroid is the only part of the body to metabolize iodine, so if Vicki's body retained any of the radioactive drink, it would mean that some of her cancerous thyroid gland remained. By using a radioactive isotope, her physicians could detect iodine uptake using a scanning device called a scintillation counter (fig. 2A). Figure 2B illustrates iodine-131 uptake in a complete thyroid gland. The next day, Vicki returned for the scan, which showed that a small amount of thyroid tissue was indeed left and was functioning. This meant another treatment would be necessary. Vicki would drink more of the radioactive iodine, enough to destroy the remaining tissue. This time she drank the solution while in an isolation room, which was lined with paper to keep her from contaminating the floor, walls, and furniture. The same physician administered the...

Extension in the Dwarf

Dwarf mice are remarkably long-lived. Congenital deficiency of growth hormone (GH), prolactin, and thyroid-stimulating hormone (TSH) due to mutations at the Pit1 or Prop1 loci, as well as GH resistance due to targeted disruption of the GH receptor gene lead to major increase in both average and maximal lifespan. Prolonged longevity of Snell dwarf (Pit1dw), Ames dwarf (Prop1df), and GHRKO mice is associated with a major extension of ''health span'' and multiple symptoms of delayed aging. Suspected mechanisms of prolonged longevity of hypopituitary and GH resistant mice include reduced peripheral levels of IGF-1 and insulin, enhanced sensitivity to insulin actions, reduced generation of reactive oxygen species, enhanced anti-oxidant defenses and stress resistance, and delayed onset of fatal neoplastic and nonneoplastic disease. Although negative correlation of body size and longevity applies to genetically normal mice and to other species, it remains to be determined whether reduced GH...

GPCR Target Validation

GPCRs have also been validated as therapeutic targets for a number of diseases based on the finding that naturally occurring mutations of the receptor can result in either a gain or loss of function of the receptor leading to an association with a disease state.30-32 An excellent review by Seifert and Wenzel-Seifert32 provides an overview of receptors that exhibit increased constitutive activity (gain of function) including (with associated disease in parentheses) rhodopsin (retinitis pigmentosa), cholecystokinin-2 receptor (gastric carcinoid tumor), KSHV-GPCR (Kaposi's sarcoma), chemokine receptor US28 (atherosclerosis), thyroid-stimulating hormone receptor (hyperthyroidism), luteinizing hormone receptor (precocious male puberty),

Calcium Deficient Bone Radiograph

Thickened Bone

Hormones secreted by the pituitary gland, thyroid gland, parathyroid glands, and ovaries or testes affect bone growth and development. The pituitary gland, for instance, secretes growth hormone, which stimulates division of cartilage cells in the epiphyseal disks. In the absence of this hormone, the long bones of the limbs fail to develop normally, and the child has pituitary dwarfism. Such a person is very short, but has normal body proportions. If excess growth hormone is released before the epiphyseal disks ossify, height may exceed 8 feet a condition called pituitary gigantism. In an adult, secretion of excess growth hormone causes a condition called acromegaly, in which the hands, feet, and jaw enlarge (see chapter 13, page 517). Thyroid hormone stimulates replacement of cartilage in the epiphyseal disks of long bones with bone tissue. Thyroid hormone can halt bone growth by causing premature ossification of the disks. Deficiency of thyroid hormone also may stunt growth, because...

Functional development of oligodendrocytes

Oligodendrocyte differentiation is regulated by a variety of growth factors. PDGF-AA is the best characterized mitogen and survival factor for OPCs. Fibrob-last growth factor 2 (FGF2) is a mitogen for OPCs and inhibits their differentiation into oligodendrocytes, at least partly by maintaining expression of PDGFaR. Expression of FGF receptors is developmentally regulated in oligodendrocytes FGF-R1 increases as cells mature FGF-R2 is expressed throughout the lineage FGF-R3 is expressed transiently by premyelinating oligodendrocytes and is important in the initiation of myelination. Insulin-like growth factor I (IGF-I) is a survival factor for oligodendrocytes and with thyroid hormone promotes differentiation. The precise interactions of these trophic factors in vivo are unresolved. When OPCs reach their final destinations, contact with axons may be sufficient for survival and differentiation, under the influence of neuregulin-1 (NRG-1) and Notch Jagged signalling.

Clinical Correlations

Anomolies The Neural Arch

Ectopic thymus, parathyroid, and thyroid tissue (Figure 11-5 D, E) result from the abnormal migration of the glands from their embryonic position to their definitive adult location. Ectopic thymus and parathyroid tissue can be found in the lateral area of the neck, whereas ectopic thyroid tissue can be found along the midline. G. Congenital hypothyroidism (cretinism Figure 11-5 F) occurs when a thyroid deficiency exists during the early fetal period due to either a severe lack of dietary iodine, thyroid agenesis, or mutations involving the biosynthesis of thyroid hormone. Figure 11-5. (A) Treacher Collins syndrome is characterized by underdevelopment of the zygomatic bones, mandibular hypoplasia (double arrows), lower eyelid colobomas, and malformed external ears (arrow). (13) Pharyngeal fistula. A radiograph after injection of a contrast medium demonstrating the course of the fistula through the neck (arrow). The fistula may begin inside the throat near the tonsils, travel through...

Vihypophysis Figure 12

A well-characterized subset of individuals with pituitary dwarfism is deficient not only in growth hormone (GH) but also in thyroid-stimulating hormone (TSH) and prolactin (PRL). The combined deficiency of GH, TSH, and PRL is caused by a genetic mutation in the Pit-1 gene, which encodes for a transcription factor called Pit-1. Pit-1 transcription factor is required for the normal transcription of GH, TSH, and PRL.

Anatomy Of A Pig Fetus

Oral Cavity Baby Pig Ventral View

Examine the nostrils (external nares) located on the the flat rostrum (snout). Open the mouth wide to expose the hard palate and the soft palate (see figs. 50.2 and 53.1). Cut through the tissues of the soft palate, and observe the nasopharynx above it. Locate the small openings of the auditory tubes in the lateral walls of the nasopharynx. Insert a probe into an opening of an auditory tube. Examine the oropharynx located near the base of the tongue. Pull the tongue posteriorly and locate the epiglottis at its base. Also identify the glottis, which is the opening into the larynx. (In the human the term glottis refers to the opening between the vocal folds within the larynx.) Locate the esophagus, which is dorsal to the larynx. Open the thoracic cavity, and expose its contents. Examine the organs located in the mediastinum. Note that the mediastinum separates the right and left lungs and pleural cavities within the thorax. Dissect the trachea in the neck, and expose the larynx at the...

Dominant Left Transverse Sinus Drains Both Superior Headache

Medical Students Stroke Syndromes

The external carotid artery has eight branches in the neck. The most important are the superior thyroid, lingual, facial, occipital, maxillary, and superficial tempo- Figure 20-1. ( ) Arterial supply of the head and neck region. (B) Lateral arteriogram and (C) lat- eral arteriogram with digital subtraction. (D) Lateral arteriogram showing a blocked internal carotid artery (arrow). The most common location of atherosclerosis in the carotid artery is at the bifurcation of the common carotid artery. Carotid artery plaques usually are ulcerated. (E) The surgical exposure used in a carotid endarterectomy within the anterior (carotid) triangle of the neck. Note the anatomic structures that may be at risk during this procedure. The incision is made along the anterior border of the sternocleidomastoid muscle, and the facial vein is ligated and cut to better expose the carotid bifurcation. Carotid endarterectomy is performed to remove blockages of the internal carotid artery. This procedure...

Endocrine System Anatomy And Physiology

Negative Feedback Mechanism Thyroid

Review textbook sections on the pituitary gland, thyroid gland, parathyroid glands, adrenal glands, pancreas, and other endocrine glands. thyroid gland parathyroid glands adrenal glands adrenal medulla adrenal cortex pancreas pineal gland thymus gland ovaries testes Figure 373 Label the features associated with the thyroid gland. Figure 373 Label the features associated with the thyroid gland. Thyroid gland. To examine the thyroid tissue, c. Prepare a labeled sketch of a representative portion of the thyroid gland in Part B of the laboratory report. Figure 37.8 Micrograph of the thyroid gland (100x micrograph enlarged to 300x). Figure 37.8 Micrograph of the thyroid gland (100x micrograph enlarged to 300x).

Nerves Of The Thoracic Wall

Intercostal Nerves

On occasion, there will be an artery that branches from the aortic arch, the right common carotid, or one of the subclavian arteries and supplies the thyroid gland in the midline. This variant artery is called a thyroid ima. Because this artery is often found crossing the region where a tracheostomy is performed, it is important to remember that this artery is present in about 10 of individuals. The left brachiocephalic vein passes anterior to the three branches of the aortic arch and is separated from the manubrium only by the thymus (Fig. 10). The brachiocephalic veins receive the internal thoracic veins, the inferior thyroid veins, and the small pericardiophrenic veins. They also receive the superior intercostal veins from behind.

Thyrotropic Hormone

Nerve Growth Factor Ngf Pathway

Like other polypeptide hormone receptors, TSH receptor is located in the cellular membrane of thyroid cells. A functional model of the TSH receptor has been hypothesized and is shown in Figure 5-35. TSHR is a seven-membrane-spanning domain receptor with a large extracellular domain. TSH binding is in the extracellular domain, and trypsinization of cells containing the receptor generates a 15-30-kDa peptide capable of binding TSH. Apparently the loops themselves are not involved in ligand binding and signaling as they are in the adrenergic receptors. The model shown in Fig. 5-35 has been derived from site-directed mutagenesis in terms of functional domains. Antibodies, especially from patients with autoimmune thyroid diseases, have been of great utility in mapping

Ovarian Germ Cell Tumors

Embryonic Cyst Ovary

Most teratomas involve only one ovary, but bilat-erality is found in about 15 of cases. Histologically, the solid teratomas are composed of various mature somatic tissues derived from all three embryonic germ layers. Glial and neural tissue may be prominent, but in contrast to immature teratomas, there are no embryonic neuroectodermal structures. Cystic teratomas are predominantly composed of skin and skin appendages, including hair and sebaceous glands. Teeth, neural tissue, retinal epithelium, many mesenchymal tissues (such as cartilage, bone, fat tissue, and muscles), and endodermal derivatives (such as bronchial and intestinal components) may be found. Thyroid tissue is the most common endocrine tissue found. Occasionally, teratomas may be associated with benign tumors such as Brenner tumor.46 Struma ovarii, composed of thyroid tissue, represents the most common monodermal teratoma (Figure 4-8). These tumors are usually solid but may be cystic, and they are often confused with...

Arteries to the Neck Head and Brain

Thyrocervical Angiogram

The thyrocervical (thiro-ser'vi-kal) arteries are short vessels that give off branches at the thyrocervical axis to the thyroid gland, parathyroid glands, larynx, trachea, esophagus, and pharynx, as well as to various muscles in the neck, shoulder, and back. The costocervical (kosto-ser'vi-kal) arteries, which are the third vessels to branch from the subclavians, carry blood to muscles in the neck, back, and thoracic wall. 1. Superior thyroid artery to the hyoid bone, larynx, and thyroid gland.

Cancer In Werner Syndrome

WS patients are at increased risk of developing cancer (Goto et al., 1996 Monnat, 2001 Monnat, 2002). The elevated risk of neoplasia in WS patients is of particular biological interest. As discussed later, neoplasia may be an expression of important mechanistic links between WRN function in vivo, genome stability assurance, and the limitation of cell proliferation defects. The elevated risk of neoplasia in WS is selective in that only a small subset of neoplasms are clearly elevated in incidence as compared with general population controls (see Table 80.2). The following neoplasms, in order of decreasing frequency, have been observed most often in WS patients and occur at higher or much higher frequency than in normal population controls soft tissue sarcomas, thyroid carcinoma, meningioma, malignant melanoma, malignant or preneoplastic hematologic disease, and osteosarcoma. Many other neoplasms, including common adult epithelial malignancies, have been observed in WS patients....

Ginseng And Atherosclerosis

Ginseng was suggested as a medicament for the control of cholesterol levels and for the treatment of anaemia. Experimental evidence does shew that ginseng is capable of increasing the red blood cell count, of promoting serum protein synthesis and of stimulating RNA formation in the liver and DNA synthesis in bone marrow. Cholesterol, a steroid alcohol, occurs naturally in the body and is found particularly in the bile and gall bladder and in the lipoproteins of the blood plasma. Although endogenous cholesterol can be formed in all cells of the body, blood cholesterol is usually produced in the liver, the body organ that controls the normal cholesterol level in the blood. High levels of cholesterol can occur in insulin and thyroid hormone deficient subjects or in persons consuming a high fat, high cholesterol containing diet. Dietary cholesterol, also called exogenous cholesterol, derives from foods such as milk, cream, butter, cheese, eggs, beef dripping, offal and other meats....

Protection of the Examining Physician

Mri Cable Burns

Most factors that serve the radiation protection of the patient also diminish the radiation exposure of the radiologist. These include the adequate experience of the examining physician, short fluoroscopy times, strict collimation of the x-ray beam, dose-minimized x-ray equipment, and a strict adherence to the indication list. One very effective protective measure is to keep the greatest possible distance (dose decreases by the square of the distance) from the primary or secondary sources of radiation (the tube and the patient). Another measure is to protect the physician with lead-lined, sometimes movable, walls, lead aprons, gloves, thyroid protectors, and awkward-looking lead-glass goggles or spectacles (Fig. 5.3). Fig. 5.3 Paul is well equipped for any radiological intervention, wearing a lead skirt that puts the weight on his iliac crests and not on his spine. The lead waistcoat, the thyroid protector, and the trendy lead goggles complete the outfit. In his hand he holds a quartz...

Microsatellite Instability

For MSI analysis, at least five repeated sequences should be tested for example, the following loci containing tetra- and pentanucleotide polymorphic tandem repeat sequences CD4 (12p13), a (TTTTC) repeat located in the 5' nontranscribed region of the T cell surface antigen gene VWA31 (12p12-pter), an (AGAT) repeat in intron 40 of the von Willebrand factor gene Fes FPS (15q25-qter), an (ATTT) repeat in intron 5 of the c-fes proto-oncogene TPOX (2p23-pter), an (AATG) repeat in intron 10 of the thyroid peroxidase gene p53 (17p13), an (AAAAT) repeat in the first intron of the TP53 gene.

Hormones Regulate Fat Mobilization

Fat Mobilization

Other hormones accelerate the release of free fatty acids from adipose tissue and raise the plasma free fatty acid concentration by increasing the rate of lipolysis of the triacylglycerol stores (Figure 25-8). These include epi-nephrine, norepinephrine, glucagon, adrenocorticotro-pic hormone (ACTH), a- and P-melanocyte-stimulat-ing hormones (MSH), thyroid-stimulating hormone (TSH), growth hormone (GH), and vasopressin. Many of these activate the hormone-sensitive lipase. For an optimal effect, most of these lipolytic processes require the presence of glucocorticoids and thyroid hormones. These hormones act in a facilitatory or permissive capacity with respect to other lipolytic endocrine factors. Thyroid hormone ' v Thyroid hormone Figure 25-8. Control of adipose tissue lipolysis. (TSH, thyroid-stimulating hormone FFA, free fatty acids.) Note the cascade sequence of reactions affording amplification at each step. The lipolytic stimulus is switched off by removal of the stimulating...

Dean Filandrinos Thomas R Yentsch and Katie L Meyers

John's wort has demonstrated clinical efficacy for mild to moderate depression and compares favorably to other more potent or toxic antidepressants. Low side effects and potential benefits warrant its use as a first-line agent for select patients with mild to moderate depression or anxiety-related conditions. Benefits related to other reported uses such as an antimicrobial, agent to treat neuropathic pain, antiinflammatory, treatment alternative for atopic dermatitis, and antioxidant are either not well documented or evidence is encouraging but not conclusive and further study is needed. St. John's wort has an inherently wide margin of safety when taken by itself, with most reported adverse drug reactions (ADRs) being related to skin reactions. Isolated, but more significant ADRs have been reported in relation to neurological effects, impact on thyroid function, and increased prothrombin time. Of greatest concern is the potential for interactions between St. John's wort and...

Ocular Use Of Steroids

Glucocorticoids have important effects on the nervous system, including behavior and intracranial pressure. Large doses of glucocorticoids have been associated with the development of peptic ulcer, possibly by suppressing the local immune response against Helicobactor pylori. Glucocorticoids given chronically suppress the pituitary release of adrenocorticotropic hormone, growth hormone, thyroid-stimulating hormone, and leutinizing hormone.

Combinations Of Genetic And Nutritional Factors

A third nutritionally related cause of MR is hypothyroidism during pregnancy. A genetic form of hypothyroidism (which, when untreated is referred to as cretinism), unrelated to iodine deficiency, can result in progressive neurological deficits after 3 months of age. In the United States, screening of all newborns is mandatory in all states and thus the occurrence of cretinism is rare. Cretinism can also result when there is maternal, fetal, or neonatal nutritional thyroid hormone deficiency the supplementation of iodine in the mother needs to occur prior to conception. Cretinism can result in neurodevelopmental deficits in the newborn, including MR and a number of other sensory and motor impairments. When both fetal and maternal hypothyroxinemia are present, such as in iodine-deficient regions of China, it has been shown that iodine replacement in the first trimester of pregnancy was necessary to prevent neurological deficits (Cao et al., 1994 Liu, Momotani, & Yoshimura, 1994...

Hierarchical and Empirical Bayes Methods for Environmental Risk Assessment

Besag et al. (1991) and Mollie (1996) considered several cancer data sets from France and England to illustrate Bayesian applications to spatial statistics and disease mapping. Besag et al. (1991) suggested posterior (marginal) modes as Bayes estimates of thyroid cancer mortality rates among women in 94 departments in mainland France during 1971-78. Mollie (1996) contrasted the EB and HB estimates for gall-bladder and bile-duct cancer mortality rates among males in the same region during the same period. In two other examples, Besag et al. (1991) also considered HB estimation of mortality among males from multiple myeloma during the same period in this region and incidence rates of any type of cancer except leukemia in the age group 0-24 in 216 wards in the Northern England. All examples showed that spatial variation or structured heterogeneity is more influential than unstructured heterogeneity in determining the disease maps except in the myeloma example where both...

Aryepiglottal Folds And Lymphoid Tissue

Arytenoid Cartilages Position

The nasopharynx lies behind the nasal cavities and above the level of the soft palate. The roof and posterior wall relate closely to the skull base and the first cervical vertebra. The lateral wall is an extension of fascia from the skull base called the pharyngobasilar fascia. The Eustachian tube opens into the lateral wall of the nasopharynx just behind and at approximately the same level as the inferior turbinate. It is lined by respiratory mucosa with accessory mucous glands, particularly numerous around the opening of the Eustachian tube. The slight depression posterior to the opening of the Eustachian tube is called the fossa of Rosenmuller (or pharyngeal recess). The oropharynx extends from the soft palate into the depth of the vallecula, the gutter between the posterior tongue and the epiglottis. The tonsillar fossa lies in the lateral aspect, between the palatoglossal and palatopharyngeal folds. The hypopharynx extends from the upper border of the epiglottis to the lower...

Typical vs Atypical Ischemia

Relatively uncommon unless they are postmenopausal, or affected by atypically high cholesterol levels or diabetes mellitus. Accelerated atherosclerosis, even in women with adequate ovarian hormonal function, can occur with hypercholesterolemia, diabetes mellitus, and rarely hypo-thyroidism with myxedema. We are not informed of this patient's menstrual history, a critical piece of information that is often not investigated during acute presentations with serious complaints in emergency rooms. However, it is reasonable to assume that at age 45 she was not postmenopausal. Moreover, she did not have a history of diabetes mellitus or hypertension. However, her physical examination did reveal a diffusely enlarged thyroid gland, but she had no complaints or physical signs of significant hypo or hyperthyroidism. Her serum cholesterol was low, which may even be secondary to hyperthyroidism, but it certainly rules out hypercholesterolemia. Despite this, she had a positive family history, with...

Anterior Mediastinal Masses

Thyroid parathyroid lesions Aberrant thyroid Thyroid goitre Thymoma the most common primary neoplasm of the mediastinum. Seventy-five per cent present in the anterior mediastinum but they can also occur in other compartments (neck, thyroid, pulmonary hilum, lung parenchyma, pleura). It is a mixture of neoplastic thymic epithelial cells and non-neoplastic lymphocytes. Tumours are evaluated on the basis of the morphology of the neoplastic epithelial cells (spindle, plump) and the relative number of these cells, compared with the non-neoplastic lymphocytic component.

Lymphoma Involving Specific Head and Neck Sites

Images Follicular Lymphoma Neck

Lymphoma involving the thyroid gland is rare, accounting for only 2 to 3 of all cases of lymphoma and less than 10 of thyroid malignancies. Women are affected more frequently than men are by a ratio of 2.7 1. The median age at presentation is over 60 years. The most common subtypes are DLBCL and follicular Grade-3 lymphoma, accounting for at least 80 of cases. A rare but interesting subtype is marginal zone B-cell lymphoma, which arises from MALT. In many cases, this lymphoma arises from a background lymphocytic infiltrate occurring in the setting of Hashimoto's thyroiditis. MALT lymphomas are low grade and clinically indolent. Hodgkin's disease may rarely involve the thyroid gland (10), sometimes as the only site of disease. Burkitt's lymphoma and follicular Grade-1 and -2 lymphomas occur less frequently (11,12). The presentation is most frequently a rapidly growing, painless neck mass, with or without adjacent lymphadenopathy (Fig. 1A and B). The more indolent...

Medicolegal Forms With Legal Analysis P-47

Related Terms Familial amyloidosis (multiple forms, including familial Mediterranean fever and familial amyloid nephropathy with urticaria and deafness hereditary cerebral angiopathies) idiopathic or primary amyloidosis (AL protein) (1) localized or isolated amyloidosis (amyloid in islets of Langerhans and insulinoma congophil cerebral angiopathy * isolated atrial amyloid medullary carcinoma of thyroid) reactive or secondary amyloidosis (AA protein) systemic senile amyloidosis.

Behavioral plasticity

To address the third question, physiological correlates of learning are known for at least several learning phenomena brain areas responsible for spatial learning are larger in males of those vole species whose spatial learning is better than females, but not in those without such a sex difference. The olfactory bulb in the brain of a young ferret during the critical period of olfactory food imprinting is larger than before or after this time. We also know that thyroxine, the hormone of the thyroid gland, is responsible for neurological changes during food imprinting in this species, and that oxytocin, a pituitary hormone, is necessary in the brain of monogamous animals to learn who their specific partner is during pair formation. Several areas in the limbic system of the brain, particularly the hippocampus, have been identified as being responsible for exploratory behavior and learning.

Conceptualization Of The Problem Of Weight Regain

A complex interaction of physiological, environmental, and psychological factors makes the maintenance of lost weight difficult to achieve. Following a period of restrictive dieting, people often experience a heightened sensitivity to palatable food (22). Consequently, exposure to an environment rich in tasty high-fat, high-calorie foods virtually guarantees occasional lapses in dietary control (23,24). Moreover, increased caloric intake during the postdieting period may easily translate into weight regain. During the postdieting period, a variety of physiological processes, including reduced metabolic rate (25-28), changes in catecholamine excretion and thyroid function (29), and increased lipoprotein lipase activity (30,31), may facilitate the regaining of lost weight. Thus, even minor periods of positive energy balance may readily result in weight gain.

Organspecific Autoimmune Disorders

Chronic thyroiditis (Hashimoto's disease, hypothyroidism) is a self-limiting disease with a probable genetic basis that affects mainly women. a. Chronic thyroiditis is characterized by autoantibodies and CMI to thyroglobu-lin or thyroid peroxidase. This reactivity causes progressive destruction of the thyroid gland. 2. Graves' disease (hyperthyroidism) is characterized by T cell and B cell infiltration of the thyroid gland, leading to the formation of autoantibodies to the thyroid-stimulating hormone (TSH) receptor. The autoantibodies may compete with TSH, bind to the TSH receptor site, and induce uncontrolled TSH-like activity. Clinical features include a diffuse goiter and thyrotoxicosis.

Physical Examination

HEENT Thin, dry, brittle hair, alopecia macroglossia (enlarged tongue), puffy face and eyelids loss of lateral third of eyebrows, papilledema, thyroid surgery scar. Jugulovenous distention (pericardial effusion). Labs Thyroid stimulating hormone, CBC, electrolytes, hypercholesterolemia, hypertriglyceridemia, creatinine phosphokinase, LDH. Autoimmune thyroiditis (Hashimoto's disease) Family or personal history of autoimmune thyroiditis or goiter History of thyroidectomy, irradiation with iodine 131, or thioamide drug therapy Subacute thyroiditis (viral) History of painful thyroid gland or neck pain Postpartum thyroiditis

Ginseng And Tumour Growth

Considering these stated criteria it is clear that ginseng has potential as a supporting agent in classical cancer therapy. The investigation of ginsengs as potential anticancer agents was undertaken by Russian pharmacologists in the 1960's and 1970's. Under experimental conditions preparations of ginseng, particularly ethereal and alcoholic extracts, and isolated ginsenosides were shewn to inhibit urethane-induced adenomas of the lung, 6-methyl-thiouracil-induced tumour of the thyroid gland and indole-induced myeloid leukaemia in laboratory animals. It was realised that ginseng could decrease the transplantability and size of tumerous foci when cells of Ehrlich's ascitic tumour were introduced intravenously into mice. The formation of spontaneous tumours of mammary gland and spontaneous leukaemia in mice could also be reduced although leukaemia-L1210 tumours were unaffected (Hou, 1978). Investigating the inhibitory effect of the phytoadaptogenic drugs bioginseng, Eleutherococcus...

Some Hormones Have Plasma Transport Proteins

The class I hormones are hydrophobic in chemical nature and thus are not very soluble in plasma. These hormones, principally the steroids and thyroid hormones, have specialized plasma transport proteins that serve several purposes. First, these proteins circumvent the solubility problem and thereby deliver the hormone to the target cell. They also provide a circulating reservoir of the hormone that can be substantial, as in the case of the thyroid hormones. Hormones, when bound to the transport proteins, cannot be metabolized, thereby prolonging their plasma half-life (t1 2). The binding affinity of a given hormone to its transporter determines the bound versus free ratio of the hormone. This is important because only the free form of a hormone is biologically active. In general, the concentration of free hormone in plasma is very low, in the range of 10-15 to 10-9 mol L. It is important to distinguish between plasma transport proteins and hormone receptors. Both bind hormones but...

Diagnosis Prion Diseases

And Hashimoto's encephalitis needs to be considered in the right clinical situation because each of these conditions is potentially treatable (Seipelt et al., 1999). While these conditions can resemble CJD clinically, they can be diagnosed by looking for antibodies to thyroglobulin, thyroid peroxi-dase, or paraneoplastic antigens (e.g., antineuronal nuclear antibodies types 1 and 2) and by cerebral spinal fluid (CSF) analysis. Viral encephalitis can be distinguished from CJD by an inflammatory pleocytosis and the detection of viral nucleic acid by polymerase chain reaction in the CSF. Hashimoto's encephalitis patients have antibodies against thyroglobulin and thyroid peroxidase in addition to normal CSF, including 14-3-3 protein analysis. Patients with paraneoplastic limbic encephalitis can be diagnosed by identifying paraneoplastic antibodies.

John M Rosenfeld Hungying Kao Ronald M Evans

Lipophilic hormones, including steroids, thyroids, and retinoids, regulate complex processes in cellular differentiation, metabolic homeosta-sis, and animal development. Their ability to diffuse into target cells and bind with high affinity and specificity to their cognate intracellular receptors allows these molecules to coordinate physiological responses by regulating the expression of gene networks. The proteins directly involved in transducing these hormonal signals are known broadly as nuclear receptors (NRs). Upon binding to their specific ligand, NRs modulate the transcription of target genes through interactions with discrete DNA-binding sites known as hormone response elements, cofactor molecules, and general transcriptional machinery. As ligand-activated transcription factors, hormone NRs are indispensable for proper growth and development and often perform essential roles in specifying cell lineages, inducing differentiation, and controlling cellular growth and function....

Metastatic Carcinoma of Unknown Primary Origin

In most patients, the site of origin of a metastatic carcinoma of unknown primary origin cannot be reliably determined by light microscopy (Hammar, 1998). Almost 60 of metastatic carcinomas of unknown primary origin are adenocarcinomas. Some metastatic adenocarcinomas (e.g., colonic adenocarcinomas) have distinctive histologic features that allow for determination of their site of origin. For most other metastatic adenocarcinomas of unknown primary origin, immunohistochemical analysis can help to identify the primary site. Immunophenotyping for cytokeratin 7, cytokeratin 20 (Chu et al, 2000), and other antigens used in conjunction with histologic analysis is effective in narrowing the potential primary site of origin of adenocarcinomas (Table 2-2), although these and other antigens are not absolutely site specific and cannot be reliably used to determine the site of origin. Other antigens that help determine the site of origin are thyroglobulin for thyroid, prostate-specific antigen...

Parental care and reproductive development

Maternal care in the rat involves the maintenance of the nest site and frequent nursing bouts over the course of the day. Milk delivery is the hallmark of the nursing bout. However, another important component of the nursing bout is the maternal licking grooming (LG) of the pups. Pup LG may be considered as a rudimentary form of parental nurturance, since this maternal behavior serves to enhance somatic growth and brain development through effects on multiple endocrine systems. Thus, the tactile stimulation associated with pup LG leads to an increased release of anabolic hormones, such as growth hormones and thyroid hormones, and decreased release of the catabolic glucocorticoids (Levine, 1994 Schanberg et al., 1984).

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