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S Shuster

Publications and source records attributed to S Shuster.

At least 37 records · Page 2Linked to original sources

Hyaluronan and CD44 expression in minor salivary gland tumors.

OBJECTIVES: Hyaluronan (HA) and CD44 are most likely associated with tumor invasion and metastasis. Malignancies with different degrees of aggressiveness may express different levels and patterns of HA and CD44. The aim of this project was to examine the distribution of HA and CD44 in minor salivary gland tumors to determine if staining could be correlated with biologic behavior or tumor type. MATERIALS AND METHODS: Biotinylated hyaluronan binding protein as a probe for HA and monoclonal antibodies specific for CD44 were used to stain classic examples of the five most commonly encountered minor salivary gland tumors: monomorphic adenomas, pleomorphic adenomas, polymorphous low grade adenocarcinomas, mucoepidermoid carcinomas, and adenoid cystic carcinomas. RESULTS: Tumor cells of monomorphic adenomas were negative for both HA and CD44, and tumor capsules were intensely HA-positive. Pleomorphic adenomas exhibited HA and CD44 positivity in both mesenchymal and epithelial components, and HA in capsular tissues. All malignant salivary gland tumors expressed similar intense HA in tumor stroma. HA staining was more intense in stroma than in parenchymal cells. Tumor cells of most adenoid cystic carcinomas were HA-positive, while most polymorphous low grade adenocarcinomas were HA-negative. HA was uniformly distributed throughout supporting stroma of high and low grade malignancies, except for two polymorphous low grade adenocarcinomas (PLGAs) in which HA was more intense at the invading edge of the tumors. CD44 expression was seen only in tumor cells (not stroma) of malignancies, and was of similar intensity in both low and high grade tumors. CONCLUSIONS: Differences in the expression of HA and CD44 among different types of salivary gland tumors were noted. These findings, however, could not be correlated with known biologic behaviors of the tumor groups studied. Immunohistochemical staining of salivary gland tumors for HA and CD44 may be useful in separating monomorphic adenoma, polymorphous low grade adenocarcinoma and adenoid cystic carcinoma, lesions that may be difficult to distinguish with routine light microscopy.

Adenocarcinoma↗

Patterns of hyaluronan staining are modified by fixation techniques.

The apparent intensity of hyaluronan (HA) staining in tissue sections can vary as a function of fixation techniques. We examined the histochemical distribution of HA in normal human skin using an HA-specific binding peptide derived from bovine nasal cartilage. The HA, particularly in the dermis, was best preserved in sections fixed in 10% acid-formalin with 70% ethanol. In contrast, sections fixed in the routine 10% neutral-buffered formalin had a much weaker intensity of HA staining. Furthermore, acid-formalin/ethanol-fixed sections retained much of their apparent HA after incubation with saline, in contrast to the neutral formalin-fixed sections, in which most of the stainable HA was lost. Such marked differences in staining intensity were not observed in slides stained with Alcian blue, a procedure presumed to stain HA as well as other glycosaminoglycans. Staining using the HA binding peptide was entirely absent when sections were first preincubated in hyaluronidase, whereas similar Alcian blue-stained sections retained most of their staining intensity. Caution should be exercised in evaluating the distribution of HA in tissues using the HA binding peptide, particularly when different fixation techniques among several laboratories are being compared. In addition, the ability to evaluate the HA content of tissues using Alcian blue staining should be reconsidered. The sulfated glycosaminolglycans of the "ground substance" appear to be the predominant substrates for Alcian blue.

Adult↗

Hyaluronan is a prerequisite for ductal branching morphogenesis.

Hyaluronan, a macromolecular carbohydrate polymer of the extracellular matrix is prominent early in embryogenesis, coinciding with rapid tissue growth. CD44, the predominant receptor for hyaluronan on vertebrate cells, is a variably expressed transmembrane glycoprotein. Mouse anterior prostate glands obtained at various postnatal time points were examined for the expression of hyaluronan and CD44. Reverse transcriptase polymerase chain reaction analysis was used to map the temporal regulation of specific CD44 variant isoforms. In each age group, hyaluronan was localized exclusively in the stromal matrix. Hyaluronan was greatly reduced in the later ages and was entirely absent around the developmentally quiescent proximal regions of the ducts. Early in prostate development, CD44 was prominent in the mesenchyme. However, in the later phases, CD44 expression became associated with membranes of epithelial cells. The role of hyaluronan-CD44 interactions in ductal branching morphogenesis was studied by serum-free organ culture of mouse anterior prostate. In the presence of optimal levels of testosterone, the organs underwent ductal branching morphogenesis. Treatment with either neutralizing anti-CD44 antibodies, hyaluronan hexasaccharides or the enzyme hyaluronidase inhibited androgen-stimulated ductal branching morphogenesis. These results are suggestive of the significant role played by hyaluronan-CD44 interactions in mediating androgen-induced prostatic growth and morphogenesis.

Animals↗

Duct disruption, a new explanation of miliaria.

From argument and a few personal observations, the hypothesis has crystallised that the miliaria commonly occurring in unacclimatised Caucasians visiting hot climates is caused by exposure to ultraviolet irradiation, by an effect on the cells of the upper epidermis, which eventually allows a split to develop between them and the new stratum corneum that grows up beneath, into which sweat from the disrupted ducts can collect as microcysts. This dehiscence is the probable explanation of sunburn peeling and photo-onycholysis. It is concluded that duct disruption, not blockage or dysfunction, is the immediate cause of the miliarias.

Apocrine Glands↗

Dermatoglyphics in Darier's disease.

Palmar and fingerprints were taken from 70 patients with Darier's disease and 409 normal controls. The dermatoglyphic characteristics of each group were determined and comparisons were made between them. Dermatoglyphic abnormalities were found; some confirmed previous findings and some were novel, but they are too small in degree and frequency to be of use diagnostically.

Darier Disease↗

Orphanin FQ/nociceptin-immunoreactive nerve fibers parallel those containing endogenous opioids in rat spinal cord.

Antisera were developed that specifically recognize orphanin FQ/nociceptin, the 17 amino acid peptide reported to be the endogenous ligand for the orphan opioid receptor. Immunocytochemical localizations in rat spinal cord demonstrated that orphanin FQ /nociceptin-immunoreactivity (-ir) was abundant in superficial dorsal horn, lateral spinal nucleus and the region dorsal to the central canal, areas that also exhibit prominent enkephalin-and dynorphin-ir. Orphanin FQ/nociceptin-ir was not affected by dorsal rhizotomy, indicating that in spinal cord the peptide is produced by central rather than primary afferent neurons. thus, the distribution of orphanin FQ/nociceptin-ir appeared in neuronal circuits that parallel those containing enkephalin- and dynorphin-ir, with only modest co-existence of these peptides.

Amino Acid Sequence↗

Jet flight leg.

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Adult↗

Hyaluronan, CD44 and its variant exons in human trophoblast invasion and placental angiogenesis.

Both hyaluronan and one of its receptors, CD44, can be demonstrated in the early human conceptus and in placental stroma. The variants of CD44 resulting from variable exon splicing are found in metastasizing human malignancies and are also involved in hyaluronan uptake and degradation. The resulting hyaluronan fragments are known to be highly angiogenic. We postulated that the self-limited process of trophoblast invasion of the uterine decidua results in part from the strategy of alternative splicing of CD44, similar to that used by invasive cancer cells in the course of metastatic spread and possibly angiogenesis. Monoclonal antibodies specific for CD44s and for an exon expressed during metastatic tumour progression, CD44v7, were used to examine this hypothesis. In this study we found human trophoblasts, for the first time, to express CD44. Intermediate trophoblasts of first and second trimester exhibited the standard form of CD44 while extravillous trophoblasts, which are responsible for the invading characteristics of the placenta, were positive for the alternatively spliced form, the CD44v7-8. Moreover, in the case of placenta accreta there was a prominent membrane staining of the trophoblasts that were embedded in the fibrin layer over the myometrium. The highly metastatic choriocarcinoma cells also expressed CD44v7-8. We propose, therefore, that the invading trophoblasts utilize the alternatively splicing machinery. These cells retain their invasive capabilities through the permissive ECM by carrying the CD44v7-8 isoform, which binds weakly to hyaluronan and thus prevents it from being degraded by intracellular hyaluronidase.

Alternative Splicing↗

Human vitreous hyaluronidase: isolation and characterization.

PURPOSE: Hyaluronic acid (HA) is the predominant glycosaminoglycan (GAG) of the human vitreous. Interaction of this HA with vitreous collagen is important for maintaining gel structure. The mechanism of HA homeostasis in the vitreous is incompletely understood. The aim of this study was to determine whether hyaluronidase, an endoglycosidase that degrades HA, was present in human vitreous. METHODS: Vitreous samples were collected from post-mortem eye bank specimens and from non-hemorrhagic, non-inflamed biopsy specimens. Vitreous hyaluronidase was purified by a series of column chromatographic steps, and its activity was measured by an ELISA-like assay and by substrate gel electrophoresis through and HA-impregnated gel. The purified hyaluronidase was also analyzed by SDS-polyacrylamide gel electrophoresis (SDS-PAGE) and by Western blotting. RESULTS: Hyaluronidase activity was detected in vitreous samples from both post-mortem and biopsy specimens. The enzyme was most active at acid pH, but demonstrated significant activity at neutral pH. The partially purified enzyme migrated as a 59 kDa protein on SDS-PAGE, and a single band on Western blots. CONCLUSIONS: Hyaluronidase is present in the human vitreous. Thus, hyaluronidase may be involved in HA catabolism in the vitreous and may play a role in determining its gel structure.

Blotting, Western↗

Patch testing with a combination of unrelated allergens: a new strategy.

A simplified method of patch testing was designed, in which several totally unrelated allergens were combined in each patch. The method was evaluated by double blind comparison of responses to 17 standard allergens applied individually as 17 conventional patch tests, and as two different sets of five patches each containing combinations of three of four allergens per patch, in 137 patients under investigation for contact allergic dermatitis. There were 89 positive responses to conventional patch testing with separate allergens and 94 and 86 positives to the two different combinations of the same allergens. Concordance of positive reactions to the two combinations was 80% and there were no irritant reactions. Conventional testing detected 70 and 74% of reactions to combination patches 1 and 2 and combination patches 1 and 2 detected 80 and 79% of the reactions to conventional testing. The combinations detected clinically relevant sensitivities not found by conventional testing. Thus, combination patch testing appears to give consistent and reliable results; its use would reduce the number of patches and increase the diagnostic yield for the specialist and permit preliminary screening by the general practitioner.

Adult↗

Capsaicin and the cause of causalgia.

From self-experimentation, I propose that the pain which occurs after application of capsaicin is causalgia and that this "capsaicin causalgia" is due to actual or functional depletion of neuropeptides such as substance P. This idea could provide an objective definition of the causalgic syndromes and improve the means of diagnosis. The analogy with capsaicin causalgia could also be extended to the pain of epidermal necrolysis, solar and thermal burns, and leprosy. The concept could lead to a better treatment of these causalgic syndromes by modulation of neuropeptide concentration or responsivity, or by mitigation of the consequences of its depletion.

Capsaicin↗