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Biomedical subjects

S Nash

Publications and source records attributed to S Nash.

53 records · Page 3Linked to original sources
PubMed1990

Structure and function of the intestinal epithelial barrier in health and disease.

The major and rate-limiting barrier to transepithelial permeation in the intestine is the intercellular tight junction. Tight junction structure is often cell type specific and general but imperfect correlates between tight junction structure and permeability exist. The structure and permeability of this key barrier is not static and can be regulated physiologically. The means of regulation appears to involve the cytoskeleton of neighboring epithelial cells (particularly absorptive cells). Meal-related solutes--nutrients such as glucose--can reversibly enhance the permeability of absorptive cell tight junctions. Although this may substantially enhance the ability of the small intestine to harvest meal-related nutrients, it is conceivable that this may also result in transient exposure of the subepithelial compartment to potentially noxious lumenal compounds. Some features found in many intestinal disease states such as PMN migration across the epithelium may also result in transient barrier defects. With PMN transmigration it is clear that even macromolecules may permeate junctions being impaled by PMNs. When disease processes finally result in focal epithelial denudation, the epithelium has the potential of resealing such defects with remarkable efficiency. The preceding discussion highlights how dynamic the tight junction is and sets the stage for future work aimed at understanding the initial signaling events and intracellular cascade(s) that allow this major barrier to demonstrate such plasticity.

Epithelial Cells↗
PubMed1989

Sexual-discrimination learning in male Japanese quail (Coturnix coturnix japonica).

We investigated how male Japanese quail (Coturnix coturnix japonica) learn through extensive social and sexual experience to discriminate between male and female conspecifics. Opportunity for heterosexual copulation was important for this learning, but even extensive copulatory opportunity was not sufficient to produce a sexual discrimination; subjects also required exposure to other males. Exposure to females after copulatory opportunity did not produce a sexual discrimination but facilitated its acquisition. Time or exposure to only the visual features of male birds (provided by taxidermic models) after copulatory opportunity did not result in differential responding to male and female conspecifics. Finally, presenting stimulus birds one at a time proved to be a more sensitive test of sexual-discrimination learning than presenting two stimulus birds at the same time. The results indicate that sexual-discrimination learning is similar to conventional associative learning.

Animals↗
PubMed1988

The selective and superoxide-independent disruption of intestinal epithelial tight junctions during leukocyte transmigration.

Polymorphonuclear leukocyte (PMN) transmigration across cultured intestinal epithelial monolayers has been shown to be associated with a decrease in transepithelial resistance to the passive flow of ions. Using flux techniques, we show that this effect reflects selective, PMN induced alterations in paracellular, as opposed to transcellular, ion permeability. Enhancement of paracellular permeability due to PMN transmigration is not simply due to expansion of the paracellular space resulting from cell death as cytotoxicity does not occur during this process. Thus, permeability alterations accompanying PMN transmigration can be specifically attributed to altered permeability of the rate limiting barrier of the paracellular pathway, the intercellular tight junction. We have also explored the mechanism by which PMN induce transient tight junction dissolution during transmigration. Use of inhibitors of toxic oxygen metabolites or use of PMN from patients with chronic granulomatous disease show that oxygen metabolites are neither required for transmigration or for the permeability abnormality accompanying transmigration. Similarly, use of protease inhibitors suggest that release of proteases by PMN during transmigration is not the basis by which PMN are able to cross tight junctions. Structural studies show that transient intimate PMN-epithelial cell plasma membrane associations and cytoskeletal specializations preceed junctional impalement by PMN. We speculate that such putative adhesion sites serve as the foothold from which PMN may generate the mechanical force necessary to cross tight junctions during transmigration.

Biological Transport, Active↗
PubMed1987

Effects of polymorphonuclear leukocyte transmigration on the barrier function of cultured intestinal epithelial monolayers.

We describe a model to study the effects of polymorphonuclear leukocyte (PMN) transmigration on the intestinal epithelial barrier. Human PMN were induced to transmigrate across high resistance monolayers of a cultured human intestinal epithelial cell line (T84 cells) by chemotactic gradients produced by formyl methionyl leucyl phenylalanine (FMLP). With maximal transmigration monolayer resistance decreased by 48 +/- 12.6% in 15 min and by 83 +/- 1.6% in 60 min. This response was dependent on the size of the FMLP gradient and the density of PMN transmigration. The decrease in resistance correlated with number of PMN migrating across monolayers, and was accompanied by increases in flux of paracellular tracers. Macromolecular tracer studies localized the leak sites to foci at which PMN impaled the epithelium. Removal of the chemotactic gradient led to restoration of baseline resistance within 18 h. PMN transmigration across intestinal epithelial monolayers occurs via intercellular occluding junctions and may be associated with a reversible increase in epithelial permeability.

Cell Line↗
PubMed1987

Effect of levamisole on the clinical and immunologic responses to oral vaccine of Treponema hyodysenteriae.

Conventionally raised crossbred Hampshire pigs were vaccinated orally with attenuated Treponema hyodysenteriae in combination with an anthelmintic, levamisole or dichlorvos. Pigs in group I (n = 9) were treated with levamisole and vaccinated with attenuated T hyodysenteriae and those in group II (n = 9) were treated with levamisole and permitted to commingle (contact exposure) with group I. Pigs in group III (n = 9) were vaccinated in a similar manner and were treated with dichlorvos. Pigs in group IV (n = 9) were treated with dichlorvos and permitted to commingle with group III. Control pigs (group V; n = 9) were not given any anthelmintic, nor were they vaccinated; they were housed separately. During the 8-week interval between vaccination and challenge inoculation, 4 total days and 8 total days of diarrhea were observed in pigs in groups I and II, respectively. Likewise, 5 total days and 10 total days of diarrhea were seen in groups III and IV, respectively. In all groups, the pigs tended to shed the organism in their feces after they were vaccinated or challenge inoculated, as determined by a fluorescent antibody technique (FAT) and culture procedure (CP). Overall mean shedding patterns of 5.5% and 24.5% identified by CP and FAT, respectively, were seen in the 2 levamisole-treated groups (I and II). In contrast, mean shedding patterns of 4% and 18% of the isolation attempts were detected by CP and FAT, respectively, in the 2 dichlorvos-treated groups. Diarrhea and shedding of T hyodysenteriae in the controls (group V) did not occur.(ABSTRACT TRUNCATED AT 250 WORDS)

Adjuvants, Immunologic↗
PubMed1986

Atypical lesions of the anal mucosa in homosexual men.

Recent studies suggest that there is an increased incidence of squamous cell carcinoma of the anus in male homosexuals, but a precursor lesion has not been identified. We retrospectively analyzed in a blind fashion all anal tissue removed surgically during 1984. Twelve (6.7%) of the 180 specimens from men contained lesions with foci of epithelial atypia. Only one (0.85%) of 118 specimens from women harbored similar atypia. Of seven additional file cases exhibiting atypical anal mucosa, six were from men. Of 14 men with atypical anal lesions whose sexual orientation was known, 11 (79%) were homosexuals. In the 20 cases found to have atypical mucosal lesions, three patterns of atypia were identified, with more than one often occurring in the same specimen. Anal intraepithelial neoplasia (dysplasia) was identified in seven cases (35%) and occurred primarily at the anorectal junction and in anal ducts. Atypical condyloma was found in three cases (15%). A third lesion histologically indistinguishable from Bowen's disease or bowenoid papulosis was found in 12 cases (60%). In ten of these the lesion was adjacent to a condyloma. Although the natural history of these lesions of the anal mucosa is presently unknown, it may resemble that of similar lesions in other anatomic locations.

Adult↗
PubMed1986

Relationship between protease activity and a sialoglycopeptide inhibitor isolated from bovine brain.

We have recently described the isolation and purification to homogeneity of a new sialoglycopeptide from bovine brain cell surfaces that reversibly inhibits protein synthesis and DNA synthesis of normal but not transformed cells. Active inhibitory preparations, however, were shown to contain a protease activity that was not lost upon purification. Several experiments were performed to establish the relationship between the proteolytic activity of the sialoglycopeptide and the biological inhibitory activity. Both the protease activity and inhibitory activity were stable at pH 6-8 but were reduced or completely destroyed below pH 4 and above pH 9. Acid inactivation was reversible and upon dialysis, both the biological inhibitory and protease activities were regained. Deglycosylation and CNBr cleavage indicated that the polypeptide backbone, rather than carbohydrate moiety, played an important role in the protease and biological inhibitory activities. Furthermore, chemical modification of amino and tyrosine groups indicated that both residues are essential for both activities. Thus, the biological inhibitory activity and protease activity are very closely related and most likely reside with the same polypeptide sequence.

Animals↗
PubMed1984

Curious neurologic sequelae in galactosemia.

Two siblings with classic transferase deficiency galactosemia that was detected at birth have been treated with lactose restriction since the neonatal period. Both patients developed a unique and progressive neurologic syndrome of mental retardation, tremor, and ataxia. Careful review of the family history and medical records, the absence of metabolic disturbances other than those related to galactosemia, and the aggregate physical findings and neurodiagnostic studies ruled out other neurologic disorders in these siblings. It is therefore proposed that these patients represent a subgroup of transferase-deficient galactosemic patients, who develop characteristic neurologic sequelae with conventional dietary management. The existence of this subgroup should be considered in evaluations of therapeutic responses in cohorts of patients with galactosemia. Further, galactosemia should be included in the differential diagnosis of tremor and ataxia in the setting of mental retardation.

Adolescent↗
PubMed1983

Identifying and tracing a population at risk: the DESAD Project experience.

In recent years, medical record review has been used to alert patients who have received drugs or treatments that have newly discovered side-effects. The experience of the national cooperative Diethylstilbestrol-Adenosis (DESAD) Project in identifying and notifying women exposed in utero to diethylstilbestrol (DES) shows this to be a difficult task. In order to identify 4,830 exposed women, 221,245 charts were reviewed. Detailed tracing data for one of the centers participating in the DESAD Project indicated that only 85 per cent of the 690 DES-exposed women identified at that center could be notified of exposure. The DESAD Project experience has led to recommendations for standardized prenatal records and drug lists, long-term storage of medical records, new legal guidelines, and improved recording of follow-up information, taking into account issues of privacy.

Adolescent↗
PubMed1982

An influenza virus matrix protein-specific human T cell line with helper activity for in vitro anti-hemagglutinin antibody production.

A human helper T cell line (F14m) activated by the matrix protein purified from A/X31 influenza virus has been developed. After activation by antigen for 7 days, and reculture with matrix protein and irradiated autologous feeder cells, the cells obtained from an in vivo influenza virus-immunized donor have been growing in the presence of interleukin 2 for more than 7 months. The cells all belong to the helper-inducer T cell subset and most of them express surface membrane HLA-DR antigens. A small number (approximately 10(3)) of F14m T cells provided optimal help for 1 X 10(5) autologous T-depleted lymphocytes for production of anti-A/X31 but not anti-B/HK antibodies. The F14m T cells produce soluble factors (S14m) able to help B cells to secrete anti-A/X31 antibodies. F14m and S14m were shown to help antibody production to hemagglutinin when cultured with B cells and the whole virus. The specificity of the T cell line for type-A matrix protein was confirmed by the ability of S14m to provide help for anti-A/JAP (A/H2/N2) but not for anti-B/HK antibody production. These data provide evidence for matrix protein-specific T helper cells and factors able to provide help for antibody production against hemagglutinin, a distinct protein of the same virus.

Antibodies, Monoclonal↗
PubMedDate not supplied

Xanthone additives for blood storage that maintain its potential for oxygen delivery. I. 2-Hydroxyethoxy- and 2-ethoxy-6-(5-tetrazoyl) xanthones in citrate-phosphate-dextrose-adenine (CPDA-1) blood.

Two xanthones, 2-hydroxyethoxy-6-(5-tetrazoyl) (BW A440C) and 2-ethoxy-6-(5-tetraozyl) (BW A827C), are members of a chemical series tested in vitro as potential additives to citrate-phosphate-dextrose-adenine (CPDA-1) medium for blood storage. P50 was maintained in the presence of these compounds during 42 days' storage by a partial maintenance of 2,3 diphosphoglycerate (2,3 DPG) and by a direct effect on hemoglobin previously reported for BW A827C. Red cell 2,3 DPG levels for BW A440C (n = 5), BW A827C (n = 5), and control (n = 6), respectively, were 3.38 +/- 0.47, 3.44 +/- 0.25, and 1.20 +/- 0.10 mM +/- SEM on day 7; 1.16 +/- 0.13, 1.52 +/- 0.37, and 0.16 +/- 0.02 mM on day 21; and 0.67 +/- 0.09, 0.61 +/- 0.08, and 0.06 +/- 0.006 mM on day 42. Red cell adenine triphosphate levels at the same time intervals were 1.84 +/- 0.09, 1.46 +/- 0.18, and 2.11 +/- 0.04 mM; 2.10 +/- 0.05, 2.07 +/- 0.17, and 2.13 +/- 0.05 mM; and 1.42 +/- 0.13, 1.37 +/- 0.13, and 1.38 +/- 0.06 mM, respectively. The degree of hemolysis was less with the addition of the compounds, and the methemoglobin formation, plasma Na+ and K+, and lactate production were unaffected by the compounds.

2,3-Diphosphoglycerate↗