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Biomedical subjects

S C Marks

Publications and source records attributed to S C Marks.

At least 91 records · Page 5Linked to original sources
PubMed1996

A regional approach to the classic metaphyseal lesion in abused infants: the proximal tibia.

OBJECTIVE: The purpose of this study was to systematically analyze the spectrum of morphologic alterations of the classic metaphyseal lesion (CML) involving the proximal tibia of abused infants and to identify features that aid in the radiologic diagnosis and assessment of healing. MATERIALS AND METHODS: Thirty-one infants who died with evidence of inflicted skeletal injury were studied with high-detail skeletal surveys, resected specimen radiography, and histopathologic analysis. The number of fractures identified, the portions of the proximal tibial metaphyses involved, and the age of the lesions were assessed. RESULTS: Seventeen proximal tibial CMLs were noted. They were bilateral in six instances and unilateral in five. When the lesion was visible radiographically, it always involved the medial aspect of the metaphysis, with involvement of the lateral metaphyseal margin in more extensive injuries. Fractures tended to be less conspicuous when acute and were more easily recognizable with healing, especially with specimen radiography. Histologically, the fracture line consistently undercut the medial subperiosteal bone collar. Extension of hypertrophic chondrocytes from the growth plate into the region of fracture was a common finding. CONCLUSION: The CML of the proximal tibia has distinctive radiologic and histopathologic characteristics that relate to the anatomy of the region. Because the proximal tibia is a common site for this strong indicator of infant abuse, the region should be carefully evaluated with well-collimated, high-detail skeletal radiographs in all cases of suspected infant abuse.

Child Abuse↗
PubMed1996

A regional approach to classic metaphyseal lesions in abused infants: the distal tibia.

OBJECTIVE: The purpose of this study was to analyze systematically the spectrum of morphologic alterations of classic metaphyseal lesions (CML) involving the distal tibia of abused infants and to identify features that assist in the radiologic diagnosis and assessment of healing. MATERIALS AND METHODS: Thirty-one infants who died with evidence of inflicted injury were studied with high-detailed skeletal surveys, resected-specimen radiography, and histopathologic analysis. The number of fractures identified, the portions of the distal tibial metaphyses involved, and the age of the lesion were assessed. RESULTS: A total of 16 CML of the distal tibia were noted. Eight infants had unilateral injury that always involved the left side, and four had bilateral lesions. When a CML was visible radiographically, it was always seen along the medial aspect of the metaphysis; lateral metaphyseal involvement was evident with more extensive injuries and always accompanied medial involvement. Fractures tended to be less conspicuous when acute and were more easily recognized with healing, especially with specimen radiography. Radiographically, the typical fracture separated a medial fragment that was tall and triangular; this appearance was histologically related to the undercutting of the long subperiosteal bone collar. In healing lesions, extension of hypertrophic chondrocytes from the growth plate into the region of the fracture was a consistent finding. CONCLUSION: CML of the distal tibia have distinctive radiologic and histopathologic characteristics that relate to the anatomy of the region. Visualization of these fractures depends on the quality of the radiographs obtained. An understanding of the radiologic and histopathologic features of CML should aid in the recognition of this strong indicator of infant abuse.

Child Abuse↗
PubMed1996

A regional approach to the classic metaphyseal lesion in abused infants: the proximal humerus.

OBJECTIVE: The purpose of this study was to systematically analyze the spectrum of morphologic alterations of the classic metaphyseal lesion (CML) involving the proximal humerus of abused infants and to identify radiologic features that aid in the diagnosis and assessment of healing. MATERIALS AND METHODS: Thirty-one infants who died with evidence of inflicted skeletal injury were studied with high-detail skeletal surveys, resected specimen radiography, and histologic analysis. In each infant, the number of fractures, the involved portions of the proximal humeral metaphyses, and the age of the lesion were assessed. RESULTS: Seven proximal humeral CMLs were seen in four infants. Radiography of the only infant with an acute injury revealed no fracture; however, evidence of trabecular disruption was found histologically. Radiographic patterns in the six healing injuries included focal corner-fracture appearance, transmetaphyseal radiolucency, irregularity of the metaphyseal margin, and flame-shaped mineralized extensions into the physeal cartilage. Histologically, all CMLs undercut the lateral subperiosteal bone collar, explaining the corner-fracture appearance. Focal and diffuse thickening of the zone of hypertrophic chondrocytes was seen, and peninsulas of primary spongiosa surrounded by hypertrophied cartilage corresponded to the flame-shaped densities revealed radiographically. The fracture morphology was better seen on specimen radiography than on skeletal survey images. CONCLUSION: CML of the proximal humerus has distinctive radiologic and histopathologic characteristics that relate to the anatomy of the region. In our study, changes at the chondroosseous junction revealed by radiography correlated well with histologic evidence of healing. Although the proximal humerus is a less common location for CML than the lower extremity, the proximal humerus should be carefully scrutinized on high-detail radiographs in cases of suspected infant abuse.

Child Abuse↗
PubMed1996

Reduced bone resorption in toothless (osteopetrotic) rats--an abnormality of osteoblasts related to their inability to activate osteoclast activity in vitro.

Osteopetrosis is a heterogeneous group of metabolic bone disorders characterized by reduced bone resorption. In the toothless (tl) osteopetrotic rat mutation there are few osteoclasts and mutants are not cured by bone marrow transplants. This suggests that the defect(s) in tl rats is within the skeletal microenvironment and not one of stem cell incompetence. Osteoblasts are known to play a role in bone resorption and abnormalities in these cells have been reported in tl rats. We explored the ability of osteoblasts from tl rats to activate resorption by normal osteoclasts when co-cultured in the presence of 1,25-dihydroxyvitamin D (1,25(OH)2D). Stimulation with 1,25(OH)2D produced a highly significant response in normal osteoblast co-cultures, but no response was observed in mutant cultures over a wide dose range. Ligand-binding studies demonstrated no abnormalities in vitamin D receptor (VDR) affinity, but mutant osteoblasts had reduced VDR numbers. Taken together with the demonstrated resistance of these mutants to the hypercalcemic effects of 1,25(OH)2D and parathyroid hormone in vivo, these data implicate osteoblasts in the pathogenesis of this mutation.

Animals↗
PubMed1996

Decreased growth hormone receptor expression in long bones from toothless (osteopetrotic) rats and restoration by treatment with colony-stimulating factor-1.

Growth hormone (GH) is known to regulate growth and development of skeletal tissues. This study examined the distribution of growth hormone receptor (GHR) expression in tibias from normal and osteopetrotic tl/tl rats. For normal 2 week-old rats, GHR expression was detected immunocytochemically in cells of the articular and epiphyseal cartilage, primary and secondary ossification centres, zone of resting cartilage and bone marrow. Within the marrow, GHR immunopositive cells were concentrated in the central cone and largely excluded from the zone of immature progenitors at the periphery. For the marrow haemopoietic compartment, GHR expression was almost restricted to the nucleus in large mononuclear cells, adipocytes and megakaryocytes. A population of small lymphocytelike cells in the marrow periphery expressed GHR on the plasma membrane. GHR was not detected in mature erythroid cells, macrophages, granulocytes, or osteoclasts. The expression of GHR was significantly reduced in bone marrow cells of the tl/tl rat (p < 0.001) compared with normal animals. Injection of recombinant CSF-1 into tl/tl rats every 48 hours for 2 weeks from birth restored GHR-positive cells to the central core of the marrow space. The most striking change was the appearance of substantial numbers of mononuclear cells expressing abundant GHR on the cell surface. We infer that these cells are a novel subset of CSF-1 responsive cells involved in bone resorption. The differences in relative expression of GHR by bone marrow cells in untreated and CSF-1-treated tl/tl rats suggests a CSF-1-dependent recruitment of cells bearing surface GHRs.

Animals↗
PubMed1996

Spontaneously hypertensive rats develop pulmonary hypertension and hypertrophy of pulmonary venous sphincters.

This study explored the spontaneously hypertensive rat as an animal model of pulmonary hypertension and sought to identify anatomic changes in its pulmonary microvasculature, especially focal constrictions of pulmonary veins (sphincters). The average systemic and pulmonary artery blood pressures were 172/139 (+/- 9/9) and 36/14 (+/- 4/3), respectively, for spontaneously hypertensive Wistar Kyoto rats (SHR), and 134/83 (+/- 8/2) and 20/10 (+/- 2/2) for normotensive Wistar Kyoto rats (WKY) (P < 0.01 for both). Light microscopy of the lungs in SHR showed muscularization of both arteries and veins, but this was more pronounced in the small pulmonary veins. Perivascular edema was also present. There were 20 (+/- 4) leukocytes per 100 microns of capillary length in SHR and 9 (+/- 2) in WKY (P < 0.001). Transmission electron microscopy showed focal venous smooth muscle was greater in SHR than in WKY. Scanning electron microscopy of vascular casts showed the average maximal focal venous contraction (sphincter) was 54% (+/- 10) of its diameter in SHR, but was only 6% (+/- 4) in WKY (P < 0.01). Arterial contraction occurred in the hypertensive rats as bourglass narrowings of the casts, but was less conspicuous than venous constrictions. The mean alveolar capillary diameter was 8.1 microns (+/- 1.6) in SHR, compared with 6.3 microns (+/- 1.0) in WKY (P < 0.01). The central interspace between capillaries was 3.2 microns (+/- 1.6) in SHR and 6.0 microns (+/- 3.6) in WKY (P < 0.01). The venous contraction, capillary size, and capillary interspace distance correlated with the pulmonary blood pressure. The spontaneously hypertensive rat can be a model of pulmonary hypertension with its most notable structural change being increased muscularity in the small pulmonary veins.

Animals↗
PubMed1996

Thrombocytopenia in the toothless (osteopetrotic) rat and its rescue by treatment with colony-stimulating factor-1.

Osteopetrosis in toothless (tl) rats is characterized by reductions in bone resorption, osteoclasts, and macrophages, resistance to cure by bone marrow transplantation, and skeletal improvement after treatment with colony-stimulating factor-1 (CSF-1). Reductions in skeletal osteocalcin tl rats, together with the recent demonstration of osteocalcin expression in platelets and its possible role in bone turnover, prompted us to examine whether this rat mutation is associated with altered platelet numbers. Our prediction of a thrombocytopenia was confirmed by examination of tl rats, in which a profound reduction (32%) in platelets was accompanied by a significant elevation (62%) in megakaryocytes (MKC) compared to normal littermates. Light and transmission electron microscopy confirmed increases in both number and size of MKC in mutants without morphologic abnormalities of circulating platelets. CSF-1 treatment (10(6) U/48 hours for 10 days) of mutants restored platelet numbers to those found normal littermates and increased osteoclasts and the frequency of MKC in numbers. Preliminary studies of another mutation the rat, osteopetrosis (op), revealed a similar reduction (33%) in platelets. These data demonstrate the coexistence of osteopetrosis and thrombocytopenia in two osteopetrotic rat mutations and an increase in osteoclasts and platelets in one mutation after CSF-1 treatment. Together, these data suggest a potential functional interaction of MKC and osteoclasts in bone turnover.

Animals↗
PubMed1996

The clinical anatomy of laparoscopic inguinal hernia repair.

Laparoscopic approaches for abdominal surgery are being used with increasing frequency. Their advantages are sometimes negated by the disturbing incidence of postoperative sequelae. In the case of inguinal hernia repair, these are often the result of failing to understand that the anatomy of the anterior approach to the abdominal wall cannot necessarily be directly applied to laparoscopy. The inguinal ligament, easily identified in an anterior approach, is only seen laparoscopically after removal of the iliopubic tract, a key structure which lies in the plane of the original defect of most groin hernias. Thus, an understanding of the incompletely trilaminar anterior abdominal wall, including the iliopubic tract, is the foundation for effective inguinal hernia repair using any approach (anterior or posterior) or technique (sutures, mesh or staples). Laparoscopic inguinal hernia repair has produced an increase in the frequency of debilitating neuropathies, most notably of the lateral femoral cutaneous nerve (LFCN). This is directly related to the variable intrapelvic course of this nerve or its branches. In more than 13% of the 114 pelves we examined, the LFCN was within 0.5 cm of the iliopubic tract or in the vertical plane of the anterior superior iliac spine, key lateral landmarks and anchoring sites for mesh in laparoscopic hernia repairs. Medial landmarks also have variable features. These data indicate that the identity of anatomical landmarks and the variability of other structures will continue to be important in the successful development of new laparoscopic techniques.

Abdominal Muscles↗
PubMed1995

Microvascular pattern in the metaphysis during bone growth.

BACKGROUND: Little is known about the three-dimensional micromorphology of vessels in the growth zone of long bones, where significant vasculogenesis occurs. Therefore, we examined the microvascular pattern of the femoral metaphysis. METHODS: Six-week-old normal rats of either sex were used. We cast the femurs of 14 rats with Mercox for scanning electron microscopy (SEM), and in 10 rats we prepared tissue sections of femurs for light (LM) and transmission electron microscopy (TEM). RESULTS: In the LM, calcified cartilage was found to define cylindrical compartments beneath the last row of hypertrophied chondrocytes of the metaphyseal growth plate. These compartments ran in the bone's longitudinal axis and contained a single capillary profile. Endothelial cells of these capillaries often showed increased cytoplasmic volume and loose texture of nuclear chromatin. Cast metaphyses by SEM showed numerous parallel vascular loops with nodular protrusions 10-12 microns in diameter at their tips. The loops had ascending and descending limbs with a luminal diameter of 10-14 microns. Small projections 4-5 microns in diameter and delicate crests were sometimes found on the tip of the larger nodes. In a 100 x 100 microns area, there were 14-17 large nodes. By TEM, capillary sprouts were identified at the level beneath the last row of hypertrophied chondrocytes. These capillaries had voluminous endothelial cells rich in free ribosomes and rough endoplasmic reticulum. Endothelial cell nuclei were rounded and showed loose chromatin texture. Endothelial cells were connected by intermediate junctions and there was no basal lamina. Deeper into the metaphysis, arterioles and sinusoids were present. CONCLUSIONS: We conclude that the metaphyseal plate of the growing rat offers an optimal model to study vasculogenesis. Capillary sprouts can be readily identified, measured, and counted because they are located within a plane bordering against avascular cartilage. In addition, by using microvascular corrosion casting in SEM not only capillary sprouting per se but also different stages of neovascularization, indicated by differently sized nodular projections at the tip of vascular loops, can be studied in the growing long bone.

Animals↗
PubMed1995

The use of multiple-choice tests in anatomy: common pitfalls and how to avoid them.

Multiple-choice questions (MCQ) are widely used to evaluate students in the health sciences, including anatomy. Unusual responses in 90 simple MCQ examinations have been identified and classified as to cause, including a number of illustrated examples. About one-quarter of these errors were attributable to the teacher and could have been avoided by a critical analysis of the questions before use. The increasing use of sophisticated formats of the MCQ in medical education indicates that teachers need to analyze their questions more carefully before and after actual tests to minimize errors.

Anatomy↗
PubMed1995

Normalization of mineral homeostasis after reversal of osteopetrosis.

Whether a radiographic and histologic cure of osteopetrosis includes normalization of mineral homeostasis remains unknown. Thus, we explored the extent of defective mineral metabolism in the microphthalmic (mi/mi) mouse before and after cure. Under basal conditions mi mutants exhibit normocalcemia, hypophosphatemia, and elevated renal 25-hydroxyvitamin D-1-hydroxylase activity. However, administration of PTHrP (3 micrograms/h x 24 h) further stimulated enzyme activity in mi mutants with active disease, to a level no different than that in treated normals. Serum phosphorus levels also declined in mi/mi mice following PTHrP, suggesting a normal renal response to this hormone. In contrast, failure to suppress enzyme function in mi/mi mice following prolonged calcitriol infusion indicates that the observed enhancement of 1,25-dihydroxyvitamin D production occurred secondary to autonomous parathyroid function and/or nonparathyroid hormone-related stimuli. Although an increased fractional excretion and decreased tubular reabsorption of phosphate were demonstrated in mi/mi mice, serum PTH levels were no different in mi mutants compared with normal littermates. Following skeletal cure, the mi/mi mice surprisingly display normal serum phosphorus levels and renal enzyme activity. Moreover, treatment restored normal responsiveness to calcitriol suppression and maintained normal PTHrP responsiveness of enzyme activity. These data indicate that the cure of osteopetrosis in the mi mutant is universal and includes normalization of serum phosphorus and renal 25-hydroxyvitamin D-1-hydroxylase. Furthermore, these data suggest that phosphate depletion of unknown origin is the likely cause of elevated enzyme activity in this murine osteopetrotic mutant.

25-Hydroxyvitamin D3 1-alpha-Hydroxylase↗
PubMed1995

Nuclear matrix-intermediate filament proteins of the dental follicle/enamel epithelium and their changes during tooth eruption in dogs.

Tooth eruption activates a localized resorption and formation of alveolar bone and these activities depend upon the adjacent parts, coronal and basal, respectively, of the dental follicle-enamel epithelium. In this study the nuclear matrix-intermediate filament (NM-IF) proteins of these tissues were isolated in order to continue investigations into the molecular mechanisms underlying eruption. Dental follicles were removed from the third and fourth premolar of dogs at 13, 16 and 20 weeks (pre-, early, and mid-to-late eruption of these teeth) and NM-IF proteins were extracted from the coronal and basal halves. Most of the NM-IF protein profiles of these coronal and basal parts on one-dimensional, sodium dodecyl sulphate-polyacrylamide gel electrophoresis were remarkably constant, indicating an essentially uniform cellular composition. However, differences between these tissues were observed and some of these changed during eruption. Based on recent observations that nuclear matrix changes reflect and may even mediate cell-specific changes in gene expression, these findings suggest that changes in nuclear matrix proteins may be related to the molecular basis for some aspects of differential gene expression in the coronal and basal regions of the dental follicle and account for the ability of these tissues to activate bone resorption and formation during tooth eruption.

Alveolar Process↗
PubMed1995

CSF-1 treatment promotes angiogenesis in the metaphysis of osteopetrotic (toothless, tl) rats.

It has recently been shown that following treatment with colony-stimulating factor-1 (CSF-1) the osteopetrotic condition in toothless (tl) rats greatly improves and growth is accelerated. We have examined the effects of such treatment on the microvasculature of the distal femoral chondro-osseous junction, a site where bone growth in length is coordinated with angiogenesis. Vascular casts and ultrastructural analyses of this region showed that, compared to untreated normal rats, untreated mutants showed little bone growth or angiogenesis. When mutants were treated with CSF-1 angiogenesis was markedly accelerated. These data show a remarkable effect of this growth factor on angiogenesis in this osteopetrotic mutation. Whether this effect of CSF-1 on angiogenesis is direct or indirect is not known and indicates that its effects on the normal microvasculature deserve further study.

Animals↗
PubMed1995

Colony-stimulating factor 1 when combined with parathyroid hormone or 1,25-dihydroxyvitamin D can produce osteoclasts in cultured neonatal metatarsals from toothless (tl-osteopetrotic) rats.

Toothless (tl-osteopetrotic) rats have little or no endogenous bone resorption, no marrow spaces, and very few osteoclasts and macrophages, and their live metatarsal rudiments cannot support the development of normal osteoclasts in vitro. The recent demonstration that exogenous colony-stimulating factor 1 (CSF-1) improves skeletal sclerosis and increases osteoclasts in tl rats in vivo, prompted us to explore conditions that enable osteoclasts to be formed in tl metatarsals in vitro. Coculture of neonatal tl metatarsals with CSF-1 alone produced no osteoclasts, but the addition of normal spleen and bone marrow cells and parathyroid hormone or 1,25-dihydroxyvitamin D produced osteoclasts in most cultures. Identical cultures of metatarsals from the CSF-1 deficient op/op mouse produced similar results. Within the contexts of the role of CSF-1 in osteoclastogenesis and the different biologic manifestations of osteopetrosis in these two mutations, we interpret these results to mean that other factors are required to restore osteoclast function completely in tl rats and op mice. Thus, experimental studies of these mutations are likely to provide new insights on both osteopetrosis and osteoclast biology.

Animals↗
PubMed1995

Bone metabolism in the osteopetrotic rat mutation microphthalmia blanc.

We have examined parameters of bone metabolism in a new mutation, microphthalmia blanc (mib), in the rat exhibiting a skeletal sclerosis at birth that improves with age. There were no significant differences in the rate of bone formation during the first postnatal month except a temporary reduction in mutants at 3 weeks that coincided with compromised nutrition at weaning. At birth the ruffled border in mutant osteoclasts was absent or poorly developed and mRNA analyses of mutant bone compared to normal bone showed significant reductions in the messages for the osteoclast-specific genes carbonic andydrase II and tartrate-resistant ATPase. These distinctive ultrastructural and molecular differences were not present 1 month later. These data show that the transient osteopetrosis in mib rats results from a perinatal reduction in ultrastructural and enzymatic features of active osteoclasts and is not complicated by elevations in bone formation. The molecular basis for both the production and resolution of these abnormalities deserves further study.

Adenosine Triphosphatases↗
PubMed1995

Administration of colony stimulating factor-1 to toothless osteopetrotic rats normalizes osteoblast, but not osteoclast, gene expression.

The toothless (tl) osteopetrotic mutation in the rat is characterized by generalized skeletal sclerosis, a severe reduction in the numbers of osteoclasts, monocytes, and macrophages, and absence of tooth eruption. Studies examining gene expression in bone-derived cells of tl rats and their normal littermates have shown that genes related to osteoblast function are aberrantly expressed in tl rats compared to normal littemates. We have previously shown that exogenous administration of colony stimulating factor-1 (CSF-1) to tl rats results in a dramatic reduction of the skeletal sclerosis and significant increases in the number of osteoclasts. Thus, we examined the effects of CSF-1 on osteoblast and osteoclast gene expression in tl rats as demonstrated by Northern blot analysis. While osteoblast-related gene expression as reflected by mRNA levels of alkaline phosphatase, osteocalcin, osteopontin, and type I collagen was normalized, osteoclast-related gene expression, as reflected by mRNA levels of carbonic anhydrase II and tartrate-resistant adenosine triphosphatase, remained significantly lower in CSF-1-treated tl rats compared to untreated normal littermates. Since previous studies have not demonstrated the CSF-1 receptor on osteoblasts, these results suggest that osteoblast abnormalities in tl rats are an effect of the osteopetrotic condition rather than the cause of the disease.

Adenosine Diphosphate↗
PubMed1995

The heterogeneity of the osteopetroses reflects the diversity of cellular influences during skeletal development.

Experimental studies of the mammalian osteopetroses, characterized by generalized skeletal sclerosis, have illuminated a variety of mechanisms by which bone resorption can be reduced. We review recent data implicating a diverse group of growth factors, proto-oncogenes, and immune regulators that can influence skeletal development and account for the heterogeneity of the osteopetroses. Furthermore, similar studies are likely to continue to provide for improved clinical management of both osteopetrotic children and the localized and generalized osteopenias.

Adjuvants, Immunologic↗