Pineal Gland Activation Course
One of the diseases carrying major 3D problems is slipped capital femoral epiphysis (SCFE), defined as the slippage of the femoral head relative to the femoral neck along the proximal femoral growth plate. This disease affects particularly the proximal femur of adolescents whose growth plate is not yet calcified and therefore is soft enough to give way for a slippage under certain circumstances. During a slippage the femoral head shifts and rotates along the proximal end of the femoral neck, usually posteriorly and inferiorly (Fig. 1). Such a slippage changes the geometry of the hip joint, leading to an incorrect position of the femoral head relative to its joint partner, the acetabulum. This misalignment is the cause of a dysfunction of the hip joint. Initially the loss of motion may be tolerated, but eventually pain and stiffness of the joint will result from early arthritic degeneration.
The pineal gland (pineal body, epiphysis cerebri) is an endocrine or neuroendocrine gland that regulates daily body rhythm. It develops from neuroectoderm of the posterior portion of the roof of the diencephalon and remains attached to the brain by a short stalk. In humans, it is located at the posterior wall of the third ventricle near the center of the brain. The pineal gland is a flattened, pine cone-shaped structure, hence its name (Fig. 20.10). It measures 5 to 8 mm high and 3 to 5 mm in diameter and weighs between 100 and 200 mg. The pineal gland contains two types of parenchymal cells pinealocytes and interstitial (glial) cells Pinealocytes are the chief cells of the pineal gland. They are arranged in clumps or cords within lobules formed by connective tissue septa that extend into the gland from the pia mater that covers its surface. These cells have a large, deeply infolded nucleus with one or more prominent nucleoli and contain lipid droplets within their cytoplasm. When...
In addition to eyes, most reptiles have a single photore-ceptive structure, a parietal organ, on the mid-dorsal aspect of the head and brain and associated with the pineal complex of the brain. Lizards and tuatara have a distinctive parietal organ called a third eye, which is equipped with a lens and a retina. These organs are thought to be ancient structures that evolved as accessory sensory systems sensitive to visible radiation. The parietal organs of living reptiles are photosensitive and appear to be involved with circadian or seasonal cycles and possibly with aspects of thermoregulation. Lightsensitive receptors are thought to be present on the skin of the tails of certain sea snakes.
The first epiphyseal center to appear is that of the distal radius, followed by those of the proximal phalanges, the metacarpals, the middle phalanges, the distal phalanges, and, finally, the ulna. There are, however, two main exceptions to this sequence the epiphysis of the distal phalanx of the thumb commonly appears at the same time as the epiphyses of the metacarpals, and the epiphysis of the middle phalanx of the fifth finger is frequently the last to ossify.
Vascular function creation of glialvascular interface bloodbrain barrier and glianeuronevascular units
The brain tissue is separated from blood by three barrier systems (1) the choroid plexus blood-CSF barrier in the ventricles of the brain, formed by tight junctions between the choroid plexus epithelial cells, which also produce the CSF (2) the arachnoid blood-CSF barrier separating the subarachnoid CSF from the blood and formed by tight junctions between the cells of the arachnoid mater surrounding the brain and (3) the blood-brain barrier between the intracerebral blood vessels and the brain parenchyma, formed by tight junctions between the endothelial cells of the blood vessels and the surrounding astroglial endfeet. The blood-brain barrier exists throughout the brain, with the exception of circumventricular organs, neurohypophysis, pineal gland, subfornical organ, and lamina terminalis, which are involved in neurosecretion and regulation of the endocrine and autonomic systems. In these parts of the brain, capillary walls are fenestrated, which allows the free exchange of large...
A child's long bones are still growing if a radiograph shows epiphyseal plates (fig. 7.11). If a plate is damaged as a result of a fracture before it ossifies, elongation of that long bone may prematurely cease, or if growth continues, it may be uneven. For this reason, injuries to the epiphyses of a young person's bones are of special concern. On the other hand, an epiphysis is sometimes altered surgically in order to equalize growth of bones that are developing at very different rates.
Fig. 11.1a This typical head CT of a 25-year-old demonstrates narrow ventricles and well-defined sulci and fissures. Calcification in the pineal gland area (arrow) is normal and develops early in life. b The typical head CT of an 85-year-old, on the other hand, shows significantly wider ventricles and external CSF spaces. In a 25-year-old this pattern would, of course, be highly pathological. One would have to consider, for example, HIV- Fig. 11.1a This typical head CT of a 25-year-old demonstrates narrow ventricles and well-defined sulci and fissures. Calcification in the pineal gland area (arrow) is normal and develops early in life. b The typical head CT of an 85-year-old, on the other hand, shows significantly wider ventricles and external CSF spaces. In a 25-year-old this pattern would, of course, be highly pathological. One would have to consider, for example, HIV-
Study the model of the sagittal section of the brain. Identify the following structures on the model aqueduct of Sylvius, cerebellum, cerebral peduncle, cerebrum, choroid plexus of the third ventricle, corpora quadrigemina, corpus callosum, fornix, gyri, hypothalamus, intermediate mass, medulla, pineal gland, pituitary gland, pons, sulci, and thalamus. Study the model of the whole brain. Identify the following structures on the model aqueduct of Sylvius, cerebellum, cerebral peduncle, cerebrum, choroid plexus of the third ventricle, corpora quadrigemina, corpus callosum, fornix, gyri, hypothalamus, intermediate mass, mammillary bodies, medulla, pineal gland, pituitary gland, pons, sulci, and thalamus. Study the wall chart of the sagittal section of the brain. Identify the following structures on the wall chart aqueduct of Sylvius, cerebellum, cerebral peduncle, cerebrum, choroid plexus of the fourth ventricle, choroid plexus of the third ventricle, corpora quadrigemina, corpus...
The midbrain is located inferior to the cerebrum and anterior to the cerebellum. The cerebral peduncles consist of a pair of cylindrical bodies that serve to connect the upper parts of the brain with lower parts of the brain and spinal cord. The corpora quadrigemina consists of four rounded lobes. The upper two are known as the superior colliculi and the lower two are known as the inferior colliculi. The aqueduct of Sylvius is a passageway that serves to connect the third ventricle and the fourth ventricle. The ventricles are discussed below. Located superiorly and slightly posterior to the corpora quadrigemina is the pineal gland. Aqueduct of Sylvius Cerebellum Cerebral peduncle Cerebrum Choroid plexus of the fourth ventricle Choroid plexus of the third ventricle Corpora quadrigemina Corpus callosum Fornix Fourth ventricle Gyrus Hypothalamus Infundibulum Intermediate mass Mammillary body Medulla Optic chiasma Pineal gland Pituitary gland Pons Sulci Thalamus Third ventricle
In humans, the pineal gland is located in the brain grossly between the thalamus and the mesencephalon, as shown in Figure 18-4. In adults the pineal is a flat, cone-shaped structure with dimensions of about 58 mm long and 3-5 mm wide and weighing around 120 mg. It is located at the posterior border of the third ventricle above the roof of the diencephalon, being connected to it by a short stalk. The pineal is covered by a layer called the pia mater. From the pia mater, connective tissue septa with blood vessels and unmyelinated nerve fibers enter the pineal to surround the cords of cells and follicles (alveoli) to form irregular lobules. Its location with respect to light stimuli is more clearly visualized in Figure 18-5. The chain of events with regard to the photoeffect is shown by light entering one of the eyes, and the signal is carried to the suprachiasmic nuclei of the hypothalamus, to the inter-omediolateral cell column of the spinal cord, then to the superior cervical...
This is a photomicrograph of an epiphysis at higher magnification than that seen in Figure 3 of Plate 13. Different zones of the cartilage of the epiphyseal plate reflect the progressive changes that occur in active growth of endochondral bone. These zones are not sharply delineated, and the boundaries between them are somewhat arbitrary. They lead toward the marrow cavity (M), so that the first zone is furthest from the cavity. There are five zones
FIGURE 6 In the axial view the anterior commissure (AC) posterior commissure (PC) appear as thin white lines connecting white matter between hemispheres. In the sagittal view the AC is a conspicuous white, slightly elliptical structure, and the PC is at the elbow between the pineal body (pb) and superior colliculus (sc). See also Plate 81.
End of the cartilage model (the epiphysis) is invaded by blood vessels and connective tissue from the periosteum (periosteal bud), and it undergoes the same changes that occurred earlier in the shaft (except that no periosteal bone forms). This same process then occurs at the other end of the bone. Consequently, at each end of the developing long bone, a cartilaginous plate (epiphyseal plate) is created that lies between two sites of bone formation. This shows an early stage after the invasion of the epiphysis. A secondary ossification center (Os) has formed, and along with this event, the head of the long bone will develop a marrow cavity similar in its content to that of the di-aphysis. The cartilage separating the two cavities is the epi
The diaphysis consists of bone (dark shading), whereas the epiphysis remains hyaline cartilage (light shtiding). This is important to note when interpreting radiographs of newborns. The radiograph of a newborn at the shoulder region (I humerus 2 acromion 3 clavicle) shows the portion of the hyaline cartilage model that has been replaced by radiodense bone (white). Note that the epiphyseal end of the humerus (white arrow) is still hyaline cartilage at birth and, therefore, will appear radiolucent (dark). The radiograph of a newborn arm and hand shows the portion of the hyaline cartilage model that has been replaced by radiodense bone (white) in the ulnar (1), radius (2), metacarpals (4), and phalanges (5). Note the epiphyseal ends of these bones (1,2, 4,5). All of the carpal bones (3) are still hyaline cartilage and, therefore, are radiolucent (dark). The carpal bones of the wrist begin to ossify much later in childhood.
N-Acetyltransferase uses acetyl-CoA to acetylate the amino moiety of arylal-kylamines. In mammalian pineal gland, this enzyme catalyzes the production of N-acetyl-5-hydroxytryptamine, which is the precursor of melatonin. It is also involved in the inactivation of monoaminergic neurotransmitters in insects.
After the testis, the next most common site for primary GCTs in males is the retroperitoneum, the anterior mediastinum, the pineal gland region, and the pre-sacrococcygeal area. There are several theories to explain the derivation of these tumors (see also Chapter 1). Some have proposed that these tumors develop within cell rests that have failed to orientate themselves properly towards the genital ridge in the embryo. In males, retroperitoneal GCTs may actually represent metastases from a testicular primary that has regressed. Mediastinal GCTs are rare, and nonseminomas are more common than seminomas. Individuals with these tumors present with shortness of breath, cough, and local discomfort and appear to have a worse prognosis than those with germ cell tumors arising at other sites.11
Njuries of the hip and pelvis in pediatric athletes are receiving increased attention. The majority of injuries are soft tissue injuries or apophyseal injuries that heal with nonoperative supportive treatment. Unique injury patterns can be seen in patients who have underlying pediatric hip disorders such as slipped capital femoral epiphysis, and Legg-Perthes disease. With the advent of hip arthroscopy and the development of more advanced imaging of the hip through MR arthrography, internal derangements of the hip such as labral tears, loose bodies, and chondral injuries are being diagnosed and treated with increased frequency. This article reviews the more common injuries of the hip and pelvis in pediatric athletes.
The pineal gland has been a topic of intense interest since antiquity, and yet its function remains somewhat obscure 1,2 . The average gland is 7.4 mm in length, 6.9 mm in width, and 2.5 mm thick 3 . It is surrounded by a capsule and is composed of lobules separated by connective tissue septae. The gland forms during the seventh week of embryonic development, when the roof plate of the primitive diencephalon thickens medially and then evaginates posteriorly. In the adult, the pineal gland is located under the splenium of the corpus callosum and over the superior colliculus. The stalk of the gland forms part of the posterior superior wall of the third ventricle and lies in between the posterior commissure and the more dorsal habenular commissure. Structurally, the stalk is composed of two laminae, a cranial or superior lamina and a caudal or inferior lamina. The pineal recess projects posteriorly into the pineal body between the two laminae. The ventricular side of the stalk of the...
Ninety-five per cent of primary intracranial GCTs originated adjacent to the III ventricle, along an axis from the suprasellar cistern (37 per cent) to the pineal gland (48 per cent). Involvement of both the sites, either sequentially or simultaneously, occurred rarely (6 per cent), as did origin within the III ventricle (3 per cent), basal ganglia-thalamus (3 per cent), or other ventricular sites (3 per cent). Germinomas preferentially involved the suprasellar region (57 per cent, including patients with multicentric involvement), while 68 per cent of NG-GCTs arose in the pineal recess (p
After adequate external examination, the brain stem and the cerebellum are separated from the cerebral hemispheres. In rare instances, it is better to retain this continuity, for example, for display of the distorting effect of a supratentorial lesion on the brain stem needs. It is essential to section through the mid-brain along a flat surface perpendicular to the neuroaxis. For this purpose, with the brain placed upside down, the cerebellum should be held between the index finger of the one hand with the tip in proximity of the pineal gland and the thumb on the inferior surface of cerebellum (Fig. 6-11). With the scalpel in a pen-holding position, the cutting hand rests on the ventral aspect of the frontal lobes to provide the proper angle. The blade is held toward the prosector with its tip in front of the distant cerebral peduncle a few millimeters above the tip of the mammillary body. The blade enters the midbrain in the mid-line, aiming toward the pineal gland until the scalpel...
We have also assessed the circadian rhythm of melatonin production (levels in the pineal gland) and excretion (levels in the surrounding water). There are two major reasons to use melatonin levels as a prospective biological marker in zebrafish aging studies. In humans, melatonin secretion is known to be highest in children of 3-5 years of age, and to decline with age. Similar age dependency of melatonin levels was documented in other species as well. In our preliminary results, adult zebrafish also have significantly lower melatonin production, compared to zebrafish larvae. We are assessing whether melatonin levels further decline in aged fish, by comparing melatonin production in young and old zebrafish. In addition, the assessment of the circadian rhythm of melatonin production is widely considered to be the most sensitive way to document individual phases of the circadian rhythm and its changes. In zebrafish, a temporal pattern of melatonin secretion can be determined by measuring...
Most inferences concerning pineal hormones and diseases have come from studies with experimental animals. Thus, pinealectomy at an early time in development in some species can lead to premature ovarian function, and treatment with melatonin can suppress ovarian function. As described earlier, the amounts of melatonin secreted nocturnally decline just prior to and during pubescence. Moreover, an acute oral dose (1-3 mg kg) given to young adults causes prolactin to be secreted. A number of different kinds of tumors can affect the function of the pineal gland, usually resulting in central nervous system disturbances and either premature or delayed gonadal functioning, especially when the tumors occur in the young.
The N-acetylation of different aryl- and arylalkylamines, using acetyl-CoA as the acetyl donor, proceeds when catalyzed by acetyl-Co A arylamine N-acetyltransferase. A natural substrate is serotonin, which is converted to N-acetylserotonin in the pineal gland and other regions of the brain.
Benign tumours relatively rare and the most common is the osteochondroma, a bony polyp with a cap of hyaline cartilage seen usually in long bones. Enchondromas are cartilaginous tumours occurring in the medullary cavity of long bones. Osteoid osteoma is a painful lesion occurring in the cortex of a long bone, with a central lytic nidus and a margin of sclerotic bone. A giant cell tumour of bone is seen in people aged 20 to 40 years of age and characteristically represents a lytic lesion occurring in the epiphysis of long bones. Other benign tumours include osteoblastoma, chondroblastoma and chondromyxoid fibroma but these are very rare.
All carpal bones and all epiphyses in the phalanges, metacarpals, radius and ulna lack ossification in the full-term newborn. The ossification centers of the capitate and hamate become apparent at about 3 months of age and remain the only useful observable features for the next six months. At about 10 months of age for girls, and about 1 year and 3 months of age for boys, a small center of ossification in the distal epiphysis of the radius appears. Due to the lack of ossification centers, assessment of skeletal maturity using hand and wrist radiographs during infancy is difficult. Estimates of bone maturation in the first year of life frequently require evaluation of the number, size and configuration of secondary ossification centers in the upper and lower extremities. Fig. 4. During Infancy, bone age is primarily based on the presence or absence of ossification of the capitate, the hamate and the distal epiph-ysis of the radius. The capitate usually appears slightly earlier than the...
And the short arm is duplicated, with symmetry around the centromere.1932 This abnormality is found in both seminomas and nonseminomas and is highly specific for GCTs. However, i(12p) has been identified rarely in other solid tumors33 and is therefore not pathognomic for GCTs. i(12p) has been identified in many EGGCTs as well, including tumors arising in the mediastinum and the pineal gland.18'20'32'34 How this genetic alteration is related to the neoplastic transformation of germ cells remains unknown.
In the instance of EGCTs, it is postulated that these cells have an aberrant path of migration in the midline,32 as a consequence of which they lodge in the pineal gland, mediastinum, retroperitoneum, or sacrococcygeum.33 It has been proposed that this migration may be triggered by c-Kit and stem cell factor receptor-ligand interactions.34 A contrasting view (because of the chromosomal similarities) is that EGCTs actually represent tumors derived by retrograde migration of carcinoma in situ (ClS)-type lesions from the genital ridges or evolving gonads.35
The proximal and distal ends of long bones are termed the epiphyses (sing. - epiphysis). The epiphyses are covered with articular cartilage (arthros Gr. joint). The term articular refers to its function (physiology). Anatomically this tissue is hyaline cartilage. The shaft of the bone is the diaphysis. Between the diaphysis and the epiphyses can be seen the epiphyseal lines, which are the remnants of the growth zones from childhood. Articular cartilage Cancellous bone Compact bone Diaphysis Endosteum Epiphysis Medullary cavity Metaphysis Periosteum Red marrow Yellow marrow 8. _ Would you look in a diaphysis or an epiphysis to find
Type lesions) 9 , developmental abnormalities from dysplasia, old slip epiphysis and Perthes disease 9 , and hip instability 10 . Developmental abnormalities such as developmental dysplasia, Perthes, and old slipped capital femoral epiphysis (SCFE) can lead to abnormal contact of the labrum 9 . Mild hip dysplasia has been identified in athletes who have lab-ral tears 2,11 . A hypertrophied labrum (Fig. 7) may also be seen during arthroscopic evaluation of the dysplastic hip.
Schematic representation of endochondral bone formation. Skeletal maturity is mainly assessed by the degree of development and ossification of the secondary ossification centers in the epiphysis Fig. 1. Schematic representation of endochondral bone formation. Skeletal maturity is mainly assessed by the degree of development and ossification of the secondary ossification centers in the epiphysis with ossification of cartilage and invasion of osteoclasts and osteoblasts. The bone ossified from the primary center is the diaphysis, while the bone ossified from the secondary center is the epiphysis. As the secondary center is progressively ossified, the cartilage is replaced by bone until only a thin layer of cartilage, the epiphyseal plate, separates the diaphyseal bone from the epiphysis. The part of the diaphysis that abuts on the epiphysis is referred to as the metaphysis and represents the growing end of the bone. As long as the epiphyseal cartilage plate persists, both the...
Schematic diagram of developing long bone. Illustrations t to 10 depict longitudinal sections la to 4a depict cross sections through the shaft of the long bone. The process begins with the formation of a cartilage model (1 and la) next, a periosteal (perichondria ) collar of bone forms around the shaft (diaphysis) of the cartilage model (2 and 2a) then, the cartilaginous matrix in the shaft begins to calcify (3 and 3a). Blood vessels and connective tissue cells then erode and invade the calcified cartilage (4 and 4a), creating a primitive marrow cavity in which remnant spicules of calcified cartilage remain at the two ends of the cavity. Endochondral bone forms on these spicules of calcified cartilage. The bone at the ends of the developing marrow cavity constitutes the metaphysis. Periosteal bone continues to form the periosteal bone is formed as the result of intramembranous ossification. It can be recognized histologically because it is not accompanied by local cartilage erosion,...
Specimen showing longitudinally sectioned epiphysis of a long bone. The outer portion of the bone has a solid structure (arrows) and represents compact (dense) bone. The interior of the bone exhibits a spongy configuration and represents spongy (cancellous) bone. It consists of numerous interconnecting bony trabeculae separated by a labyrinth of interconnecting marrow spaces. epiphysis metaphysis metaphysis-epiphysis -
Photomicrograph of human pineal gland. This higher-magnification photomicrograph shows the characteristic concretions called brain sand or corpora arenacea. Pinealocytes (chief cells of the pineal gland) account for the majority of the cells seen in the specimen. They are arranged in clumps or cords. Those blood vessels (BV) that contain red blood cells are readily apparent numerous other blood vessels are also present but are not recognized at this magnification without evidence of the blood cells. x250.
It has been observed that serum melatonin levels decline during continued development, so that there is an apparent relationship between pineal gland function and development in general. During gestation, maternal melatonin crosses the placenta, and after birth, maternal melatonin is passed to the infant through the milk. Full circadian rhythm of these
Specimen showing longitudinally sectioned epiphysis of a long bone. The outer portion of the bone has a solid structure (arrows) and represents compact (dense) bone. The interior of the bone exhibits a spongy configuration and represents spongy (cancellous) bone. It consists of numerous interconnecting bony trabeculae separated by a labyrinth of interconnecting marrow spaces. epiphysis metaphysis
Depiction of the progressive growth of the epiphyses, which, during this stage of development, become larger than the metaphyses. Special attention is also placed on epiphyseal shape, which, prior to epiphyseal fusion, overlaps the meta-physes, depicting tiny hornlike structures at both ends of the epiphysis (picture at far-right) Fig. 8. Depiction of the progressive growth of the epiphyses, which, during this stage of development, become larger than the metaphyses. Special attention is also placed on epiphyseal shape, which, prior to epiphyseal fusion, overlaps the meta-physes, depicting tiny hornlike structures at both ends of the epiphysis (picture at far-right)
The human pineal gland starts as an evagination of the roof of the third ventricle in the second month of gestation. The pineal anlage, the ependyna, a lobular structure, fuses into a solid and becomes invested with vascular connective tissue, giving a lobular appearance to the pineal parenchyma. The pineal gland then changes from a vertical to a horizontal organ and becomes innervated. In neonates, the pineal is shown to consist of two cell types, type I and type II. Type I cells
Rare cases of EGGCTs have been reported in a variety of locations, including the prostate,21 the seminal vesicle,22 the iliac fossa,23 and the liver.24 However, the majority of cases occur in midline locations, including the mediastinum, the sacrococcyx, and the pineal gland. While true primary EGGCTs occur in the retroperitoneum as well, many investigators (for the reasons discussed above) consider this group as originating from gonadal primary tumors.
Ninety-five percent of intracranial germ cell tumors (ICGCTs) arise in the region of the third ventricle, along an axis from the suprasellar cistern to the pineal gland. The most common site involved is the pineal gland, followed closely by the suprasellar region. Rarely, these tumors present within the third ventricle, basal ganglia, thalamus, or other ventricular sites.27 Germinomas (a term used for intracranial seminoma) preferentially involve the suprasellar region whereas nonseminomatous tumors tend to involve the pineal gland. Approximately 5 to 10 of cases will present in both locations, and these are usually germinomas.28 Clinical symptoms are based mostly on the size of the tumor and on its primary location. Pineal gland tumors most commonly present with symptoms due to increased intracranial pressure caused by obstruction of the third ventricle these symptoms include hydrocephalus, Parinaud's syndrome (upward-gaze paralysis, pupillary areflexia, and lack of convergence),...
The pineal (so named for its pinecone shape) gland is rather unique with respect to the magnitude of change characterizing its evolutionary development. In amphibians it is primarily a photoreceptive organ, but in higher forms it has evolved from this state to a gland producing hormones that receives light information by way of the lateral eyes and sympathetic nerves. Pineal products include melatonin, other methoxyin-doles, serotonin, and acetylserotonin (see Figure 18-1). Although vasotocin has been reported to be a pineal product, it is not clear whether significant amounts of vasotocin are actually synthesized in the pineal gland. Production of the methoxyindoles is dependent on light or darkness, and these hormones have been shown to regulate seasonal reproductive activities. There is some difference of opinion concerning the primacy of the pineal hormones with regard to physiological action. Melatonin is currently thought to be the principal active substance produced by the...
The adenosine A3 receptor was found to be expressed in different tumor cell lines, including Jurkat T, pineal gland, astrocytoma, melanoma, and colon and prostate carcinoma cells,86 suggesting it may serve as a target for tumor growth inhibition. Activation of the A3 receptor, however, was shown to attenuate growth of melano-cytes both in vitro and in vivo as well as colon carcinoma growth in mice through modulation of the Wnt signaling pathway linked to the TCF LEF p-catenin path-way.87 Activation of the A3 receptor may be beneficial for therapeutic intervention of certain tumors.
Disc of hyaline cartilage-the epiphyseal plate-separates the more proximally located epiphysis from the funnel-shaped diaphysis located distal to the plate. The articular cartilage on the surface of the epiphysis contributes to the synovial joint and is also composed of hyaline cartilage. Whereas the cartilage of the epiphyseal plate disappears when lengthwise growth of the bone is completed, the articular cartilage remains throughout life. The spaces within the bone are occupied by marrow. x85.