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L S Shapiro

Publications and source records attributed to L S Shapiro.

15 recordsLinked to original sources

Development of NADPH-diaphorase expression in chemosensory systems of the opossum, Monodelphis domestica.

Using NADPH-diaphorase histochemistry, the present study describes development of olfactory and vomeronasal systems in postnatal opossums, Monodelphis domestica. NADPH-dependent staining is absent at and around the time of birth. By 2 weeks of age and through adulthood, intense staining is seen along the luminal surface of the olfactory epithelium (OE) and of the vomeronasal sensory epithelium (VNE), as well as in Bowman's glands of the OE. Staining of the adult VNE is not homogeneous; it is restricted to the superficial 2/3 of the epithelium. At 2 weeks of age, staining in the brain is seen only at the surface of the ventricles and in blood vessels. At 1 month of age and through adulthood, staining of varying intensity is seen in individual olfactory bulb glomeruli, although the incoming olfactory axons are relatively unstained. Interestingly, whereas at 30 days of age, staining of the accessory olfactory bulb (AOB) glomeruli is uniform, 2 weeks later and in the adult, NADPH staining is concentrated in the rostral half, with little or no staining observed in the posterior portion. Darkly stained periglomerular cells are seen throughout the extent of the differentially-stained glomerular layer. From 30 days of age and through adulthood, intense NADPH staining is also observed in the islands of Calleja, as well as in cells of the dorsal cortex, often associated with the path of the rostral migratory stream.

Aging↗

Segregated pathways in the vomeronasal system.

The vomeronasal system of mammals is chemoarchitecturally dichotomous. Two populations of receptor cells have been identified in the vomeronasal sensory epithelium based on the family of receptor proteins they express on their membranes. These two receptor cell populations express different G-proteins: the more basal population expresses Goalpha and the more apical population expresses Gialpha2. The Goalpha-expressing receptor cells project their axons to the posterior accessory olfactory bulb (AOB) whereas the Gialpha2-expressing cells project their axons to the anterior AOB. In all mammals studied to date, the anterior AOB is Gialpha2-positive and the posterior AOB is Goalpha-positive. These two parts of the AOB are also chemoarchitecturally heterogeneous with respect to their carbohydrate content as revealed both with lectin binding and immunoreactivity to monoclonal antibodies raised against carbohydrate moieties. However, species differences have been observed with respect to lectin binding, as with NADPH-diaphorase reactions and OMP immunoreactivity. Recent studies indicate that there are physiological and behavioral correlates to the dichotomy within the vomeronasal system.

Animals↗

Heterogeneity in the accessory olfactory system.

The mammalian accessory olfactory bulb (AOB) is chemoarchitecturally heterogeneous in that it stains differentially with a number of markers; the receptor cells that project to the AOB are similarly heterogeneous. What is the significance of this heterogeneity? We have found that the AOB of the gray, short-tailed opossum, Monodelphis domestica, stains differentially with a number of 'markers': antibodies to olfactory marker protein (OMP) and the alpha subunit of the G protein Gi2, the lectin of Vicia villosa and NADPH-diaphorase. These markers stain the rostral AOB more strongly than the caudal AOB whereas, the G protein subunit G(o) alpha is located predominantly in the posterior subdivision of the AOB. This heterogeneity in the chemoarchitecture of the AOB may reflect a fundamental organizational dichotomy within the vomeronasal system that corresponds to a functional dichotomy. The vomeronasal sensory epithelium also exhibits a chemoarchitectural heterogeneity: receptor cells in the basal third are G(o) alpha-immunoreactive whereas the cells in the middle third are Gi2 alpha-immunoreactive. Tracing studies using WGA-HRP demonstrate that the neurons in the middle third of the vomeronasal sensory epithelium project their axons to the anterior AOB whereas those in the basal third appear to project to the posterior AOB.

Animals↗

Development of olfactory marker protein and N-CAM expression in chemosensory systems of the opossum, Monodelphis domestica.

Using olfactory marker protein (OMP) and neural cell adhesion molecule (N-CAM) immunohistochemistry, the present study describes development of olfactory and vomeronasal systems in pre- and postnatal opossums, Monodelphis domestica. As revealed by OMP expression, development of the main olfactory system precedes that of the vomeronasal system by 1-2 weeks. OMP is expressed throughout (homogeneously) the nerve and glomerular layers of the main (MOB) but is expressed more strongly (heterogeneously) in the anterior as compared to the posterior accessory (AOB) olfactory bulb. N-CAM expression is homogeneous in both MOB and AOB. The heterogeneity in the AOB is developmentally regulated, since in the 30-day-old AOB the expression of OMP is homogeneous, becoming heterogeneous during the second month of life. Maximal expression of N-CAM precedes maximal expression of OMP in the VNS by about 2 weeks. From 7 to 21 days of age only, there is a small population of OMP-positive, N-CAM-negative olfactory and vomeronasal axon terminals that penetrate deep into the brain parenchyma, overgrowing their normal targets in the MOB and AOB, respectively.

Age Factors↗

Vomeronasal system involvement in response to conspecific odors in adult male opossums, Monodelphis domestica.

The present study was designed to test the hypothesis that preferential nuzzling of unfamiliar conspecific odors by male opossums is vomeronasally mediated. Opossums were presented with vials containing their own odors (Own) and vials with odors from unfamiliar conspecifics (Novel) both before and after (Expt. 1) or only after (Expt. 2) vomeronasal nerve (VNNX) or sham (Sham) surgery. Nuzzling duration was greater for Novel before (Expt. 1) and after (Expts. 1 and 2) surgery both in VNNX and Sham animals, indicating that a functional vomeronasal system is not necessary for the differential nuzzling of novel odors. In contrast, differential scent marking of Novel was lost following VNNX, but not following sham surgery. Since VNNX lesions disrupt differential marking behavior but, not differential nuzzling, it is possible that different components of conspecific odors guide these two chemosensory behaviors and that these components may be detected by different sensory systems. Vomeronasal nerve lesions, confirmed histologically, resulted in the loss of the beta-NADPH-dependent reaction product from the accessory olfactory bulbs (AOB). The pattern of staining with 4 lectins, soybean agglutinin (SBA), Phosphocarpus tetragonolobus (PCT), Vicia villosa agglutinin (VVA), and Griffonia simplicifolia lectin I-isolectin B4 (GS I-B4) remained unchanged in the AOB following vomeronasal nerve lesions, although the size of the AOB appeared to decrease in the VNNX animals.

Animals↗

Isolated pulmonary hypertension in systemic sclerosis with diffuse cutaneous involvement: association with serum anti-U3RNP antibody.

OBJECTIVE: To describe a group of patients with systemic sclerosis (SSc) and diffuse cutaneous (dc) involvement with isolated pulmonary hypertension (IPHT) and to compare them to 2 other SSc patient groups, i.e., one with limited cutaneous (lc) involvement with IPHT and another with dcSSc without IPHT. METHODS: The Pittsburgh Scleroderma Databank was screened to identify appropriate patients. SSc specific serum autoantibodies were determined using published methods. Chi-squared tests and Kaplan-Meier survival analysis were performed. RESULTS: During the period 1975-92, 60 of 580 (10%) consecutive new patients with lcSSc and 14 of 677 (2%) with dcSSc have developed IPHT (p < 0.0001). The patients with IPHT did not differ from their parent dc or lc groups by age, race, sex, or cutaneous manifestations. All 14 patients with dcSSc IPHT had minimal or no pulmonary interstitial fibrosis on chest radiograph. The 12 tested had a striking reduction in DLCO (mean 50% of predicted normal), similar to results for patients with lcSSc with IPHT. Of note, 5 of these 14 patients had survived "scleroderma renal crisis" 1.3 to 10.7 (mean 5.5) years before onset of IPHT. Six of 13 (46%) patients with dcSSc with IPHT were positive for serum anti-U3RNP antibody by immunoprecipitation, and one had the typical nucleolar staining pattern of anti-U3RNP, but was not tested for U3RNP by immunoprecipitation. In contrast, only 13 (6%) of the 244 patients with dcSSc without IPHT (p < 0.0001) had anti-U3RNP antibody. Survival from the first reported symptom consistent with pulmonary hypertension (usually dyspnea on exertion) was uniformly poor in both IPHT groups, with the vast majority of patients dying during the first 2 years. CONCLUSION: Patients with SSc with dc involvement can develop severe, fatal isolated pulmonary arterial hypertension. This complication occurs disproportionately more often in patients with serum anti-U3RNP antibody.

Adult↗

Differential localization of G proteins in the opossum vomeronasal system.

Gi2 alpha and G(o) alpha proteins were immunohistochemically localized, respectively, to the rostral and caudal accessory olfactory bulb of Brazilian opossums. In the vomeronasal organ, Gi2 alpha- and G(o) alpha-immunoreactive neurons were located in the middle and basal layers, respectively, of the sensory epithelium. Both G protein antibodies stained the microvillar surface of the epithelium and the nerve bundles in the subepithelial mucosa.

Animals↗

Lectin histochemical identification of carbohydrate moieties in opossum chemosensory systems during development, with special emphasis on VVA-identified subdivisions in the accessory olfactory bulb.

Lectins, sugar-binding molecules of nonimmune origin, were used in this study to describe the development of the main olfactory and vomeronasal systems in the Brazilian gray short-tailed opossum, Monodelphis domestica. A battery of seven lectins of the N-acetylgalactosamine/galactose-binding group was used. Of the seven lectins, only two, Vicia villosa agglutinin (VVA) and Griffonia (Bandeiraea) simplicifolia lectin I-isolectin B4 (GS I-B4), were specific to the vomeronasal system. The other five lectins recognized carbohydrates in both chemosensory systems, although the binding was more intense in the accessory olfactory system. Furthermore, whereas six of the lectins stained the adult opossum accessory olfactory bulb (AOB) homogeneously, the VVA lectin distinguished two regions of the AOB. Similar to the expression of olfactory marker protein (OMP) (Shnayder et al. [1993] Neuroreport 5:193-196), the rostral half of the AOB stained much darker with VVA than the caudal half, and the onset of the restricted pattern of staining at age 45 days also coincided. We conclude that 1) GS I-B4 and VVA recognize cell surface carbohydrate moieties specific to the vomeronasal, but not to the main olfactory, system, and 2) the carbohydrate moiety that is recognized by the VVA lectin, presumably terminal N-acetyl-galactosamine, is both temporally and spatially restricted in the opossum AOB. These results are discussed in the framework of other known spatially restricted molecules of the two major nasal chemosensory systems.

Acetylgalactosamine↗

Large vessel arterial thrombosis in systemic sclerosis associated with antiphospholipid antibodies.

A 69-year-old woman with systemic sclerosis developed thrombosis of each superficial femoral artery requiring above-knee amputations. On pathologic examination of the involved vessels, atherosclerotic changes were minimal and thrombus formation was the primary abnormality. The presence of antiphospholipid antibody suggested an acquired predisposition to vascular thrombosis. Prior reports of large vessel thrombosis in systemic sclerosis are reviewed.

Aged↗

Pulmonic regurgitation due to valvular tophi.

Documented cardiac tophi are rare and have not previously been reported to cause clinically manifest valvular disease. A 31-year-old male with complex cyanotic congenital heart disease (Taussig-Bing anomaly) and secondary tophaceous gouty arthritis is described. Terminally, he presented with clinical evidence of a brain abscess and a new semilunar regurgitant murmur. Two-dimensional echocardiography suggested vegetative lesions as the cause of the murmur. The patient was treated for infective endocarditis. At autopsy, the cause of the semilunar regurgitant murmur was shown to be sterile tophi located along the line of pulmonary valvular coaptation. Tophaceous deposits were also present in the mitral valve.

Adult↗

D-penicillamine treatment of progressive systemic sclerosis (scleroderma): a comparison of clinical and in vitro effects.

Punch biopsies of skin were obtained from the forearms of 3 patients with progressive systemic sclerosis with diffuse scleroderma before and after treatment for 1 year or more with D-penicillamine. While on therapy, each patient studied had demonstrated a marked reduction in skin thickening. Collagenase-sensitive protein and glycosaminoglycan accumulation were measured in fibroblast cultures derived from these biopsies. No differences were observed pre- and post-treatment. We conclude that although D-penicillamine may exert its effect in vivo on connective tissue synthesis, maturation and/or turnover, fibroblasts remaining in the thinned dermis retain their potential for increased synthesis of connective tissue.

Adult↗

Isolation and preliminary characterization of clathrin-associated proteins.

Clathrin-associated proteins were separated from clathrin under various clathrin-denaturing conditions, i.e. heating, freezing and isoelectric precipitation. The proteins retained biological activity; they were purified further by affinity chromatography on calmodulin-conjugated CNBr-Sepharose 4B and used for antibody purification. The affinity-purified anti-(clathrin-associated proteins) antibodies gave a fluorescent dotted pattern in cultured fibroblasts consistent with the known distribution of clathrin. Chemical cross-linking of pure clathrin-associated proteins indicated that these polypeptides exist as monomers in solution, each possessing Ca2+-dependent affinity for calmodulin to which they bind in a 1:1 molar ratio. Chymotryptic treatment of coated vesicles selectively cleaved the clathrin-associated proteins into a 15 000-18 000-Mr doublet polypeptide. These subfragments retained their Ca2+-dependent affinity for calmodulin. Our results support a regulatory role for clathrin-associated proteins in clathrin assemblies.

Calcium↗