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S C Marks

Publications and source records attributed to S C Marks.

At least 109 records · Page 6Linked to original sources

Endothelin-1 focally constricts pulmonary veins in rats.

Serum endothelin levels increase during sepsis, ischemia, reperfusion, pulmonary operations, and systemic hypertension after surgery. Despite extensive study, the site and extent of action of endothelin on the pulmonary microcirculation are not well established. To assess the effect of endothelin on the pulmonary vasculature, especially the veins, the circulation of the lung was cast with methyl methacrylate 10 minutes after endothelin-1 was given intravenously to rats. Endothelin-1, at concentrations of 0.1, 1.0, and 10.0 micrograms/kg of body weight, increased the mean systemic arterial blood pressure 8%, 7%, and 17% (p < 0.01) and mean pulmonary arterial blood pressure 15%, 28%, and 53%, respectively (p < 0.01). The proportional increases in the pulmonary pressures were greater than those of the systemic pressures (p < 0.01). Scanning electron microscopy of cast blood vessels showed more contraction of the veins than the arteries. For doses of 0, 0.1, 1.0, and 10.0 micrograms/kg, the respective focal contraction of small veins was 6.7% (+/- 4.4), 15.4% (+/- 9.1), 23.3% (+/- 10.1), and 14.4% (+/- 9.0) of the vessel diameter (p < 0.01). In addition, the diameter of capillaries increased (p < 0.01) and the capillary interspaces decreased (p < 0.01) after endothelin administration, but not in a linear dose-dependent manner. The dose of endothelin correlated with the change in the mean systemic (r = 0.82, p < 0.01) and the mean pulmonary (r = 0.80, p < 0.01) blood pressures. The mean pulmonary pressure change correlated with the focal venous contraction on the casts (r = 0.35, p < 0.01), capillary diameter (r = 0.64, p < 0.01), and capillary interspace distance (r = -0.34, p < 0.01). The venous contraction was related to the capillary diameter (r = 0.26, p < 0.01). The most notable effect of endothelin-1 in rat pulmonary microcirculation is focal constriction of small veins. Because this effect may lead to pulmonary edema, endothelin antagonists may be of benefit in a variety of clinical situations.

Analysis of Variance↗

Osteoblasts from the toothless (osteopetrotic) mutation in the rat are unable to direct bone resorption by normal osteoclasts in response to 1,25-dihydroxyvitamin D.

Osteopetrosis describes a diversified group of metabolic bone disorders characterized by a generalized, skeletal sclerosis resulting from reduced osteoclast-mediated bone resorption. The toothless (tl) osteopetrotic mutation in the rat is characterized by few osteoclasts and the inability to be cured by transplants of hemopoietic stem cells. This implies that the defect(s) responsible for reduced osteoclast activity in tl rats is within the skeletal microenvironment (cells or matrices). Osteoblasts and their products are known to play a role in regulating bone resorption and abnormalities in the osteoblast population in tl rats have been reported. The purpose of this study was to determine whether osteoblasts isolated from tl mutant rats, when cultured with normal osteoclasts, could increase bone resorption (pit formation) in response to stimulation by 1,25 dihydroxyvitamin D (1,25(OH)2D). The addition of 1,25(OH)2D produced a highly significant response in normal osteoblast cocultures but no response in mutant cultures. A dose response study with 1,25(OH)2D (10(-6) to 10(-9)M) revealed that mutant osteoblasts are unable to increase osteoclast activity. These data indicate that the vitamin D receptor-signal transduction pathway in tl rats needs to be examined.

Animals↗

Bafilomycin A1 in bone resorption and tooth eruption in dogs.

Tooth eruption depends on bone resorption to form an eruption pathway. We have previously shown that a 2-wk local infusion of bafilomycin A1, an inhibitor of vacuolar H(+)-ATPases in osteoclasts, into the crypts of erupting mandibular premolars in dogs blocks bone resorption during this period and eruption of these teeth is delayed for 8 wk. Here we report the limits of inhibition of resorption that still permit eruption of these teeth. In 3 dogs 10(-6) M bafilomycin was delivered by osmotic minipumps early (18 wk) in eruption to the fourth premolar for 1, 3 or 4 wk. Radiographs taken at weekly intervals thereafter showed that bafilomycin delivery for 1 wk delayed eruption for 3 wk, delivery for 3 wk delayed eruption 9 wk and delivery for 4 wk prevented eruption. These data show that tooth eruption is delayed in direct proportion to the time resorption is blocked, and that this process for dog premolars cannot be blocked for more than 3 wk with 10(-6) M bafilomycin without blocking eruption itself.

Alveolar Process↗

Bacteriology of sinusitis in human immunodeficiency virus-positive patients: implications for management.

The bacteriology of sinusitis in human immunodeficiency virus (HIV)-infected patients has been only sporadically reported. In this study, we report the results of cultures taken from 12 HIV patients with refractory chronic sinusitis who underwent surgery. Nine of the 12 patients had positive cultures with 16 isolates and 5 patients having multiple isolates. Five of the 12 patients grew out atypical or opportunistic infections not responsive to standard medical therapy, including 3 patients with cytomegalovirus, 1 with Aspergillus fumigatus, and 1 with Mycobacterium kansasii. These results suggest the need for aggressive medical care for HIV-infected patients with sinusitis and early intervention for tissue cultures in patients who do not respond to standard antibiotic regimens.

AIDS-Related Opportunistic Infections↗

Relationship of the subperiosteal bone collar to metaphyseal lesions in abused infants.

We studied the relationship between the subperiosteal bone collar and forty metaphyseal lesions in specimens obtained at autopsy from ten infants who died with evidence of abuse. The fracture specimens were studied with high-detail radiography and light microscopy. The typical morphological pattern was a fracture extending through the primary spongiosa adjacent to the chondro-osseous junction. As the fracture line approached the cortex, it veered away from the growth plate, undercutting a fragment of bone that was thicker peripherally than it was centrally. Histological examination showed that this peripheral fragment of bone included the subperiosteal bone collar. Inclusion of the subperiosteal bone collar within the peripheral portion of the metaphyseal fracture fragment explains the radiographic appearance of corner fractures and bucket-handle patterns described by Caffey in abused infants.

Bone Marrow↗

Why perirenal disease does not extend into the pelvis: the importance of closure of the cone of the renal fasciae.

OBJECTIVE: The prevailing concept is that lack of fusion of the anterior and posterior renal fasciae caudally (an open cone) allows free communication between the perirenal space and the extraperitoneal portion of the pelvis. However, perirenal disease rarely extends into the pelvis and an open cone has not been observed on CT scans. Accordingly, we determined the anatomy of the caudal extent of the cone of the renal fasciae in cadavers and on CT scans. MATERIALS AND METHODS: Anatomic dissections of the lower portion of the retroperitoneum and the extraperitoneal portion of the pelvis were made in eight cadavers. Two cadavers were intact, two had colored latex injected into the perirenal space before dissections, and the abdomens and pelves of four were sectioned transversely in 3- to 5-cm-thick slices. The renal fasciae were traced on transparent films placed on the cross sections, and computer-generated three-dimensional representations of the tracings were made. These anatomic findings were correlated with observations made on CT scans of 59 consecutive patients with diseases involving the lower part of the retroperitoneum and the extraperitoneal portion of the pelvis (32 patients with hemorrhage, 16 with inflammatory processes, and 11 with neoplastic conditions). RESULTS: The anatomic study showed that the anterior and posterior renal fasciae merge to form a single multilaminar fascia in the iliac fossa. Anteriorly, this common fascia is loosely connected to the parietal peritoneum. Posteriorly lies the caudal continuation of the posterior pararenal compartment. This joins with the laterocaudal continuation of the central part of the retroperitoneum, which contains the iliac vessels. The distal part of the ureter lies within the caudal continuation of the single multilayered renal fascia. The CT studies done in patients showed that extension of the perirenal processes to the pelvis and vice versa was both restrained and uncommon: no direct extension of any abnormalities was observed in either direction, and laminar thickening of the fasciae was seen in one fifth of the patients. Similarly, no inferior communication of the perirenal space with the anterior or posterior pararenal spaces was seen. CONCLUSION: There is an anatomic barrier between the inferior perirenal space and the extraperitoneal pelvis formed by the fusion of the leaves of the renal fasciae into a single multilaminar fascia that acts as a barrier of disease extension. The multilaminar nature of this fascia, however, may also act as a filter, allowing some permeability between its layers. This potential interlaminar pathway is rare and is manifested as fascial thickening on CT scans. This laminar filter-barrier observation explains the lack of extension of perirenal diseases into the pelvis.

Adult↗

Inflicted skeletal injury: a postmortem radiologic-histopathologic study in 31 infants.

OBJECTIVE: The objective of this postmortem study was to use high-detail skeletal surveys, specimen radiography, and histopathologic analysis to determine the number, distribution, and age of inflicted skeletal injuries in infants studied at the University of Massachusetts Medical Center from 1984 to 1994. MATERIALS AND METHODS: Thirty-one infants (average age, 3 months) who died with inflicted skeletal injuries were studied with high-detail skeletal surveys and specimen radiography and histopathologic analysis. The distribution and number of fractures was determined for each technique, and dating was performed on the basis of radiologic and histologic criteria. The skull fractures noted in 13 cases were excluded from the numerical analysis. RESULTS: The radiologic-histopathologic correlation revealed 165 fractures involving the ribs in 84 (51%), long bones in 72 (44%), bones of the hands and feet in 6 (4%), clavicles in 2 (1%), and spine in 1 (< 1%). Of the 72 long bone fractures, the metaphyses were involved in 64 (89%, or 39% of the total), and the shaft was involved in 8 (11%, or 5% of the total). One hundred sixteen fractures were healing, 36 were acute, and 13 were of indeterminate age. In all but two infants, at least one healing fracture was present. Of fractures diagnosed histopathologically, specimen radiography increased the yield of fractures noted on skeletal survey from 58% to 92%. CONCLUSION: Most infants who die with inflicted injury have fractures at multiple sites. Metaphyseal and rib fractures are much more common than long bone shaft injuries, the opposite of the pattern found in older children. Because most abused infants who die have evidence of healing fractures at the time of autopsy, aggressive radiologic efforts to identify these injuries in living as well as in decreased infants appear justified.

Autopsy↗

The basic and applied biology of tooth eruption.

The dentition and the alveolar process of each jaw develop simultaneously so that, by the time the crown is completed and eruption begins, the crown is enclosed in a crypt within alveolar bone. Thus, the eruption of a tooth to its functional position involves discretely localized, bilaterally symmetrical bone resorption to produce an eruption pathway and bone formation to fill in the space previously occupied by the crown and growing roots. Studies of crypt surfaces during eruption confirm this polarization of alveolar bone metabolism around a tooth with respect to both bone cells and mineralized surface topography. Experimental studies of tooth eruption have shown that the dental follicle, the dense connective tissue investment of the tooth, is necessary for eruption and that neither bone resorption nor bone formation occur without the adjacent part of the dental follicle. Early in eruption the coronal part of the follicle accumulates mononuclear cells which have cytochemical and ultrastructural features of osteoclasts and the apical part of the follicle, a site of intense cell proliferation, binds epidermal growth factor (EGF). The dental follicle contains a variety of proteins and the concentration of several change during eruption. Prominent among them are a reduction in matrix metalloproteinases and an increase in protoglycans as eruption proceeds. The contribution of these changes to those in cell proliferation, migration and differentiation during tooth eruption present experimental opportunities for developmental biologists. The rate-limiting factor of the earliest (intraosseous) stage of tooth eruption is bone resorption and eruption can be accelerated or retarded by the local delivery of factors which increase or decrease the activity of osteoclasts.(ABSTRACT TRUNCATED AT 250 WORDS)

Alveolar Process↗

Altering tooth eruption by blocking bone resorption--the local delivery of bafilomycin A1.

Tooth eruption is a complicated process requiring a coordination of bone resorption and bone formation by a variety of factors in and around the dental follicle proper and bone resorption is the rate-limiting step early in the process. We have recently described a method to deliver to the crypt of erupting dog premolars a reversible blocker of bone resorption, bafilomycin A1, and shown that its delivery for two week blocks bone resorption and eruption during this period without effect on adjacent teeth or on bone formation. In this study we show that delivery of 10(-6) M bafilomycin A1 via a cannulated osmotic minipump for two weeks early in the eruption of premolars delayed the eruption of these teeth for eight weeks. Similar delivery of the vehicle to the contralateral premolar had no effect on eruption. These data are the first clinical application of this potent drug and show that a short term local delivery is reversible and that blocking resorption for two weeks causes a fourfold delay in tooth eruption. Modifications of this approach may have clinical applications in dentistry.

Animals↗

The contrasting effects of colony-stimulating factor-1 and epidermal growth factor on tooth eruption in the rat.

Both epidermal growth factor (EGF) and colony-stimulating factor-1 (CSF-1) have been shown to accelerate eruption of teeth in rodents. We compared the effects of neonatal injections of EGF (1 micrograms/g body weight) and CSF-1 (10(6) units) alone or together on the eruption of incisors and first molars. EGF accelerated the eruption of incisors with no significant effect on first molars. CSF-1, in contrast, accelerated molar eruption more than incisor eruption. CSF-1, but not EGF, increased the numbers of mononuclear cells in the dental follicle and osteoclasts on adjacent alveolar bone surfaces around the first molar and produced enhanced resorption of crypt surfaces as revealed by scanning electron microscopy. These data suggest that during eruption rodent incisors and molars may preferentially respond to different molecular regulators.

Alveolar Process↗

Collagen metabolism and tooth eruption: the effects of sodium morrhuate infusions on premolar eruption in dogs.

To test the essential contribution to tooth eruption of the known high level of collagen metabolism in the periodontal ligament, we have infused the crypts of erupting premolars in dogs with sodium morrhuate, a compound known to reduce production, hydroxyproline content and maturation of collagen. Infusions of sodium morrhuate early or later in eruption for more than half the period of eruption had no effect on the process evaluated radiographically and clinically. These data, considered together with other studies, suggest that collagen metabolism per se plays no essential role in tooth eruption.

Animals↗

The mechanisms and mediators of tooth eruption--models for developmental biologists.

Tooth eruption is a localized process in the jaws which exhibits precise timing and bilateral symmetry. It involves resorption and formation of bone on opposite sides of the erupting tooth and these activities depend on the dental follicle, a thin connective tissue investment of the developing and erupting tooth. Biochemical studies have shown that during eruption cells, proteins and enzymes change in the dental follicle and several growth factors and proteins known to accelerate or retard eruption have been identified. This review discusses these aspects of tooth eruption and proposes testable hypotheses and strategies that can make studies of tooth eruption new experimental opportunities for developmental biologists.

Animals↗

Colony-stimulating factor-1 injections improve but do not cure skeletal sclerosis in osteopetrotic (op) mice.

The osteopetrotic (op) mutation in mice is characterized by general skeletal sclerosis; reduced numbers of osteoclasts, macrophages, and monocytes; and failure to be cured by bone marrow transplantation. This mutation has been shown to result from an absence of colony-stimulating factor-1 (CSF-1) and reported to be cured by treatment with CSF-1. Contrary to previous reports, we have noted persistent metaphyseal sclerosis in op mice treated with CSF-1 at doses above physiological concentrations of circulating CSF-1. We pursued this observation by quantitating osteoclasts and macrophages in the first 500 microns (area A) and the subsequent 1000 microns (area B) in the proximal tibial metaphysis using tartrate-resistant acid phosphatase and F4/80 as cell markers. In untreated normal mice, osteoclasts and macrophages were found in areas A (9.1 and 13.8 cells/1000 microns2) and B (4.1 and 9.4 cells/1000 microns2), respectively. In untreated mutants, osteoclasts and macrophages as percentages of normal were, respectively, 0% and 2% (area A) and 30% and 13% (area B). After CSF-1 treatment (0.15, 0.3, 0.5, and 1.0 x 10(6) U/day) for 28 days, marrow cavity size and numbers of osteoclasts and macrophages increased significantly in area B. However, area A remained sclerotic, with few macrophages (3% to 20%), and although osteoclast numbers were normal, their distribution was not, being absent in subepiphyseal sites. High CSF-1 gene expression occurs at bone modeling sites, co-localizes with osteoblasts, and temporally correlates with their differentiation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Carotid artery resection for cancer of the head and neck.

OBJECTIVE: To compare the morbidity and mortality associated with ligation and reconstruction of the carotid artery after resection. DESIGN: Cohort study. SETTING: Tertiary referral center and Veterans Affairs medical center. PATIENTS: Twenty consecutive patients who underwent carotid artery resection for metastatic squamous cell carcinoma between January 1985 and June 1992. RESULTS: Seven (58%) of 12 patients with ligation suffered neurological sequelae compared with one (13%) of eight patients with interposition grafts (P < .05). Six of eight patients with neurological sequelae had delayed onset of complications. Local control of tumor was achieved in 14 (74%) of 19 patients overall. Median survival was 6.3 months, and the 1-year disease-free survival rate was 16% (three patients). CONCLUSION: Carotid artery replacement is superior to ligation in avoiding the neurological complications of carotid artery resection. Carotid artery resection can provide local control of tumor but fails to achieve a high rate of disease-free survival.

Adult↗

The epithelial attachment and the dental junctional epithelium: ultrastructural features in porcine molars.

The region of epithelial apposition with a tooth surface is the site of an unusual stratified integument, the junctional epithelium, which combines tight attachment to the tooth, cell turnover, tissue permeability, and epithelial versatility into the first line of defense against periodontal destruction by oral pathogens. To better understand the structure and function of the junctional epithelium we have reviewed its developmental and cell biology, and undertaken a multidisciplinary analysis of its composition in the pig, an omnivore whose dietary and dental development and occlusion patterns are similar to the human condition, and which, because of its size, is more readily amenable to experimental manipulation. The porcine junctional epithelium was also compared with this well-described epithelium in the rat. Morphological analyses by light microscopy and scanning and transmission electron microscopy showed the porcine junctional epithelium and epithelial attachment were similar to that in the rat except that apically, extracellular matrix lamellae associated with the internal basal lamina were more complex, and more coronally there was extensive layering of a dental cuticle-like material. Biochemical analysis of the porcine junctional epithelium by dissociative extraction and SDS-PAGE revealed the presence of some proteins not present in gingival epithelium. Together, these studies show that the porcine junctional epithelium has predictable morphological and biochemical features which establish the pig as an advantageous model to study the basic and clinical biology of this unique epithelium.

Animals↗

Evaluation of urinary pyridinium crosslink excretion as a marker of bone resorption in the rat.

The aim of this study was to evaluate the value of the urinary excretion of the pyridinium crosslinks, pyridinoline (Pyr) and deoxypyridinoline (D-Pyr), as markers of bone resorption in the rat. The excretion of the crosslinks was compared with that of urinary [3H]tetracycline ([3H]TC) excretion from chronically [3H]TC-prelabeled animals, a technique established to monitor bone resorption in the rat. Bone resorption was modulated by Ca restriction, infusion of PTH, thyroparathyroidectomy, and administration of different bisphosphonates. Furthermore, the urinary crosslinks were assessed in three different osteopetrotic mutations in the rat. We found a delayed response of Pyr and D-Pyr excretion to acute changes in bone resorption compared with [3H]TC excretion. This delay was 1 day after Ca restriction and longer after other treatments, such as PTH administration or bisphosphonate treatment, with which it was more than 3 weeks. In contrast, chronic states with stimulation or inhibition of bone resorption showed similar changes in excretion of the urinary crosslinks and [3H]TC, except after PTH administration. The excretion of the crosslinks was greatly reduced in osteopetrotic rats (op/op, tl/tl, and ia/ia) and increased to normal levels in tl/tl rats after stimulation of bone resorption by M-CSF administration. These results suggest that, in rats, urinary excretion of the pyridinium crosslinks reflects bone resorption in chronic but not always in acute conditions. The cause of this discrepancy is still unclear.

Amino Acids↗

Bafilomycin A1 inhibits bone resorption and tooth eruption in vivo.

It has been shown that a specific inhibitor of vacuolar H(+)-ATPases, bafilomycin A1, inhibits bone resorption by isolated chicken osteoclasts by blocking the proton pump in the ruffled border membrane. We report here the effects of bafilomycin A1 on bone resorption in vivo. Using a cannulated osmotic minipump delivery system, we infused bafilomycin locally to the eruption pathway of permanent premolars of beagle dogs. We used pit formation by osteoclasts in vitro to estimate the concentrations and heat stability of bafilomycin to be used in vivo. In this model, osteoclasts were cultured on thin bone slices, in which they form pits indicative of resorption. After 2 weeks preincubation at 37 degrees C, bafilomycin concentrations of 10(-6) and 10(-7) M but not 10(-8) M completely inhibited the resorptive activity of cultured osteoclasts, and the two larger doses were chosen for use in vivo. Local delivery of 10(-6) M bafilomycin to the eruption pathway of the fourth permanent mandibular premolar during mideruption inhibited tooth eruption by blocking bone resorption as assayed by radiography, light microscopy, and scanning electron microscopy. Bafilomycin at 10(-7) M had similar but less intensive effects. Moreover, osteoclasts in the alveolar bone of crypts treated with 10(-7) M bafilomycin A1 stained very weakly for tartrate-resistant acid phosphatase. The effect of bafilomycin on bone resorption was shown to be very local, and no side effects of treatment with bafilomycin were observed in adjacent teeth or the behavior of dogs. We report here, for the first time, inhibition of tooth eruption caused by inhibited bone resorption using bafilomycin A1 in vivo.

Animals↗