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S Shaw

Publications and source records attributed to S Shaw.

At least 217 records · Page 12Linked to original sources
PubMed1994

Costimulation by purified intercellular adhesion molecule 1 and lymphocyte function-associated antigen 3 induces distinct proliferation, cytokine and cell surface antigen profiles in human "naive" and "memory" CD4+ T cells.

Activation of resting human CD4+ "naive" (CD45RA+CD45RO-) and "memory" (CD45RA-CD45RO+) T cells requires costimulatory signals in addition to engagement of the T cell receptor/CD3 complex (TCR/CD3). The adhesion pathways mediated by lymphocyte function-associated antigen 1/intercellular adhesion molecule 1 (LFA-1/ICAM-1) and CD2/LFA-3 are capable of providing such costimulatory signals. Our work shows that these costimulatory adhesion pathways are critically involved in regulation of T cell differentiation/maturation. Evidence for subset-specific costimulatory requirements is demonstrated by the finding that only memory CD4+ T cells were costimulated by LFA-3, whereas both naive and memory CD4+ T cells were costimulated by ICAM-1. In addition, these costimulatory adhesion pathways regulated reciprocal cytokine secretion patterns for interleukin 5 (IL-5) and granulocyte/macrophage colony-stimulating factor (GM-CSF). Repeated costimulation of CD4+ memory T cells with LFA-3 led to secretion of high levels of IL-5, while repeated costimulation with ICAM-1 induced high levels of secreted GM-CSF. Significant interferon gamma (IFN-gamma) production was observed with either of the costimulatory ligands. Extensive cell surface analysis of these in vitro cultures of peripheral blood derived memory CD4+ T cells, with monoclonal antibodies obtained from the 5th Leucocyte Typing Workshop, revealed differential expression of a singular antigen, CD60. This antigen was preferentially expressed on LFA-3-costimulated cells suggesting a positive correlation between CD60 expression and a T helper type 2-like cytokine profile. In conclusion, this report demonstrates a new functional role for costimulatory adhesion molecules in regulating differential cytokine secretion in human memory CD4+ T cells.

Antibodies, Monoclonal↗
PubMed1994

Hepatocyte growth factor and macrophage inflammatory protein 1 beta: structurally distinct cytokines that induce rapid cytoskeletal changes and subset-preferential migration in T cells.

T-cell migration into tissue depends on a cascade of rapid and selective adhesive interactions with endothelium. "Triggering" is a step in that cascade required to activate T-cell integrins. Hepatocyte growth factor (HGF) may be a physiologically relevant trigger, since we demonstrate that HGF can induce both adhesion and migration of human T-cell subsets and can be detected immunohistochemically on inflamed endothelium. HGF preferentially induces responses from T cells of memory phenotype, in contrast to macrophage inflammatory protein 1 beta (MIP-1 beta), a chemokine which acts preferentially on naive cells. HGF, like the chemokines, binds to heparin, and HGF retained in extracellular matrix is efficient in promoting migration. Further, both MIP-1 beta and HGF induce actin polymerization within seconds, kinetics that approach those required to contribute to physiologic triggering. HGF is a member of a structural family distinct from the chemokines, whose only known receptor is the tyrosine kinase c-Met. HGF induces tyrosine phosphorylation on T cells apparently via a distinct receptor, since no c-Met is detectable by surface staining, PCR, or anti-phosphotyrosine immunoprecipitation. Thus, promotion of T-cell adhesion and migration are previously undescribed functions of HGF that we propose are relevant to selective T-cell recruitment.

Cell Adhesion↗
PubMed1994

CD antigens 1993.

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Antibodies, Monoclonal↗
PubMed1994

CD antigens 1993.

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Antigens, CD↗
PubMed1994

CD45RB expression defines two interconvertible subsets of human CD4+ T cells with memory function.

Reciprocal expression of CD45RA and CD45RO in human CD4+ T cells defines populations understood to be naive cells (CD45RA+CD45RO-) and memory cells (CD45RA-CD45RO+). We investigate two subsets of CD45RA-CD45RO+ CD4+ human T cells which differ by fourfold in their expression of the CD45RB isoform; one is CD45RBbright and the other is CD45RBintermediate. In contrast, CD45RA+ naive cells are all CD45RBbright. Both subsets of CD45RA- cells proliferate in response to recall antigens so we designate them MEM 1 (CD45RO+RBbright) and MEM 2 (CD45RO+RBintermediate). CD45RA and CD45RB expression are regulated independently during in vitro activation of naive cells. When MEM 1 cells are activated they tend to down-regulate CD45RB expression, whereas activated MEM 2 cells tend to up-regulate CD45RB expression. Thus, in contrast to the stability of the CD45RA-CD45RO+ phenotype, the MEM 1 and MEM 2 phenotypes are labile and may interconvert. MEM 1 and MEM 2 cells produced comparable amounts of interleukin(IL)-2, IL-4, and IL-5 though MEM 1 cells produced slightly more interferon(IFN)-gamma (mean 1.7-fold more). MEM 1 cells consistently proliferated more (mean 2.3-fold more) than MEM 2 cells early during in vitro activation. Thus, differential expression of CD45RB within CD45RA- cells defines two subsets that have similar properties except for somewhat greater IFN-gamma production and proliferative responses by MEM 1 cells. Variability in CD45RB expression may represent a mechanism for fine-tuning the responsiveness of memory cells in vivo.

CD4-Positive T-Lymphocytes↗
PubMed1994

Most free-radical injury is iron-related: it is promoted by iron, hemin, holoferritin and vitamin C, and inhibited by desferoxamine and apoferritin.

Iron is a double-edged sword. In moderate quantities and leashed to protein, it is an essential element in all cell metabolism and growth, but it is toxic when unleashed. Because of its ability to switch back and forth between ferrous and ferric oxidation states, iron is both a strong biological oxidant and reductant. The human diet contains a multitude of natural chemicals which are carcinogens and anticarcinogens, many of which act by generating oxygen radicals, which initiate degenerative processes related to cancer, heart disease and aging (the "oxygen radical hypothesis of aging"). Among these many dietary chemicals are many redox agents, including vitamin C and beta carotene. Free radical damage is produced primarily by the hydroxyl radical (.OH). Most of the .OH generated in vivo comes from iron-dependent reduction of H2O2. Supporting too much iron as a free radical-generating culprit in the risk of cancer, NHANES I data indicated that high body iron stores, manifested by increased transferrin saturation, are associated with an increased cancer risk. Other data shows an increased heart attack risk.

Animals↗
PubMed1994

Molecular analysis of an HLA-DP mutant cell line selected for its resistance to killing by HLA-DPw2-specific T-cell clones.

A collection of HLA-DP mutants was generated, using ICR 191 as the mutagenic agent and resistance to lysis mediated by HLA-DPw2 allospecific cytotoxic T lymphocytes (CTLs) as the selection criterion. These mutants were derived from the HLA haploid lymphoblastoid cell line 45.1. Loss of HLA-DPw2 surface expression accounted for the lack of HLA-DPw2 CTL recognition in all the mutants. However, one of them, 45.EM19, binds to DPw2-specific monoclonal antibodies (mAb) after cell permeabilization. HLA-DPA1 and DPB1 mRNA expression studies permitted the classification of the mutants in four categories: 1) DPA1-negative, DPB1-positive; 2) DPA1-positive, DPB1-negative; 3) DPA1- and DPB1-negative, and 4) DPA1- and DPB1-positive mutants. Mutant 45.EM19 is included in the last group. The cloning and sequencing of the full-length DPA1 (DPA1*0103) and DPB1 (DPB1*02012) cDNAs from this mutant showed no changes in the DPA1 sequence compared to the wild-type sequence. However, a frame-shift mutation in the DPB1 gene exon coding for the transmembrane region was detected. The insertion of a guanine nucleotide provokes an extension of the open reading frame, increasing the length of the C-terminal domain and changing the hydropathicity pattern of the transmembrane domain. This change should be responsible for the phenotype of the 45.EM19 mutant.

Amino Acid Sequence↗
PubMed1994

CD antigens 1993.

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Antigens, CD↗
PubMed1994

A comparison study of the EF-18 agar/Hydrophobic Grid Membrane Filter (HGMF) method and the enzyme linked antibody (ELA)/HGMF method to the HPB standard method in the isolation of Salmonella.

As part of a comparative and collaborative study of rapid methods for the detection of Salmonella and the standard Health Protection Branch (HPB) method, six Federal and Provincial Laboratories compared the EF-18 agar/Hydrophobic Grid Membrane Filters (HGMF) method to the standard HPB method. Two Federal Laboratories also compared the enzyme linked antibody (ELA)/HGMF method (which is a further development of the EF-18 agar/HGMF method) to the standard method. During this study the false-negative rates ranged from 0% to 15% for the standard HPB method, from 5.88% to 43.5% for the EF-18 agar/HGMF method, and from 0% to 10.5% for the ELA/HGMF method. The EF-18 agar/HGMF method did not compare well with the standard HPB method due to the number of false-negatives. Problems with this method resulted from the inability to isolate colonies of Salmonella on the HGMF due to the small colony size, abnormal colony coloration, and overgrowth by competitors. The ELA/HGMF method, however, was shown to be comparable to the standard HPB method. The main advantages of this method are that the antibody-staining step is independent of colony coloration and carbohydrate utilization on the plating media; the ability to detect some unusual strains of Salmonella irrespective of their atypical reactions on the media; and the ELA staining can indicate the presence of Salmonella even when the HGMF is overgrown by competitors. Also, cultural confirmation can proceed simultaneously yet independently of the ELA staining procedure. The data presented here indicate that this method is worth further study.

Bacteriological Techniques↗
PubMed1994

Acute sodium loading in patients with uncomplicated diabetes mellitus: renal and hormonal effects.

1. Diabetes mellitus is associated with high body sodium, but the pathogenetic mechanism is still unknown. The possibility that an abnormal renal handling of sodium, an abnormal responsiveness of sodium-modulating factors or a shift in the set point for sodium metabolism may contribute to or be associated with sodium retention was tested with an acute saline infusion. 2. A consecutive sample of 33 patients with stable non-azotaemic diabetes mellitus (24 insulin-dependent patients) and 30 normal control subjects was studied. Two litres of a 0.9% NaCl infusion were infused over 4 h. The urinary sodium excretion during the infusion and the next 18 h was analysed in relation to blood pressure, creatinine and lithium clearances, Na(+)-K+ co-transport, Na(+)-Li+ countertransport, plasma levels of renin, angiotensin II, aldosterone, noradrenaline, adrenaline, atrial natriuretic factor and digoxin-like factor. 3. Diabetic patients and control subjects did not differ in blood pressure, body mass index, clearances of creatinine, sodium or lithium, intracellular sodium Na(+)-K+ co-transport and Na(+)-Li+ countertransport, urinary and plasma levels of digoxin-like factor, plasma renin activity, angiotensin II, aldosterone, noradrenaline, adrenaline and atrial natriuretic factor. The intravenous saline infusion caused a similar natriuresis in diabetic patients and normal subjects; the renin-angiotensin-aldosterone system was suppressed to a higher degree in diabetic patients than in normal subjects, whereas atrial natriuretic factor was stimulated to a similar extent; plasma digoxin-like activity was unchanged in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

T cell subpopulation phenotypes in filarial infections: CD27 negativity defines a population greatly enriched for Th2 cells.

Three-color flow cytometric analysis was used to define surface markers which identify the Th2-type CD4+ cells responsible for the eosinophilia and elevated serum IgE typical of tissue invasive helminth infections. A group of six mAbs to well known cell surface markers were screened for differential expression on CD4+ CD45RO+ lymphocytes from normal individuals (NL; n = 6) and filaria-infected patients (PT; n = 10). The majority of markers were expressed equally by both groups, but the CD4+ CD45RO+ cells in the PTs showed significantly higher levels of expression of HLA-DR than those of NLs (P = 0.014). This CD4+ HLA-DR+ subpopulation was then studied further for its expression of an additional 10 activation and adhesion molecules. CD27 showed a trend for lower intensities of expression on PT CD4+ HLA-DR+ cells than on those of NLs. Analysis of the serum from both NLs and PTs revealed that PTs had significantly higher levels of soluble CD27 and CD25 (IL-2R) in the serum than NLs (P < 0.01 and P = 0.022 respectively) indicating a general state of immune activation and differentiation. Functional analysis of the CD4+ HLA-DR+ and the CD4+ CD27- subpopulations revealed that the CD4+ HLA-DR+ cells produced significantly higher levels of IL-5 than the CD4+ HLA-DR- cells (P = 0.04), and the CD4+ CD27- cells produced significantly higher levels of both IL-4 and IL-5 than the CD4+ CD27+ cells (P < 0.05 and P < 0.001 respectively). Thus, while the CD4+ CD27- and CD27+ subpopulations contain Th1 and Th0 cells, only the CD4+ CD27- population contains the Th2 cells (producing both IL-4 and IL-5).

Antigens, Surface↗
PubMed1994

Insulin sensitivity and atrial natriuretic factor during beta-receptor modulation with celiprolol in normal subjects.

beta-Receptor blockers may exert a spectrum of metabolic and humoral effects, which might differ depending on the specific adrenoreceptor characteristics of the individual agents. We investigated the influence of celiprolol, a beta 1-blocker with beta 2-agonistic and, possibly, additional weak alpha-receptor antagonistic properties, on insulin sensitivity (SI), glucose homeostasis, and lipid profile in 20 young, healthy, normotensive individuals. SI, fasting plasma glucose and insulin, serum total triglycerides (TG), lipoprotein cholesterol (C) fractions, lipoprotein a [Lp(a)], and plasma atrial natriuretic factor (ANF) levels were determined before and after acute glucose loading under placebo conditions and after 3 weeks of celiprolol administration. The participants were instructed to follow a 3-day standard diet (2,500 kcal/day, 45% carbohydrates, 40% fat, and 15% protein) and an overnight fast before measurements were recorded. As compared with control values, SI, fasting plasma glucose and insulin, the areas under the glucose and insulin curves, the k value of glucose disappearance after glucose load, and serum cholesterol fractions, TG, and Lp(a) were unchanged during celiprolol administration. However, celiprolol significantly reduced plasma ANF levels (p < 0.02). The latter increased in response to acute hyperglycemia/hyperinsulinemia with placebo (p < 0.05) but not with celiprolol. Although diastolic blood pressure (DBP) decreased slightly during the first and second week of celiprolol administration, BP and heart rate (HR) did not differ significantly after 3 weeks on celiprolol treatment as compared with placebo conditions. Our findings demonstrate that in healthy lean humans beta-receptor modulation with celiprolol is neutral with regard to SI and lipoprotein metabolism. Moreover, glucose loading stimulates whereas celiprolol decreases plasma ANF levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-1 Receptor Antagonists↗
PubMed1994

DETECTION OF AIRBORNE SOUND BY A COCKROACH 'VIBRATION DETECTOR': A POSSIBLE MISSING LINK IN INSECT AUDITORY EVOLUTION

Extracellular recordings from nerve 5 in metathoracic legs of Periplaneta americana disclose a sense organ that is extremely responsive to vibration but also detects sound (best response near 1.8 kHz) with a sensitivity similar to some insect auditory organs. The energy required from an auditory signal for a criterion response is similar or even smaller than for an optimal vibratory input. Responses originate in the subgenual organs (SGO) in the proximal tibiae, and cross-modal adaptation indicates that the same cells respond to both vibration and sound. Sound is picked up directly on some internal structure, not via sound-induced substratum vibration. Adaptation at different frequencies discloses no frequency-selectivity in the SGO. The nerve response is a burst of synchronized impulses at a frequency, fR, of approximately 300 Hz, that is practically invariant both with sound intensity and within the burst, suggesting that fR might represent some underlying resonance phenomenon, either of the SGO or of air in the tracheal system. The latter possibility is ruled out by observations made while the tracheae are perfused with He&shy;O2. Similar responses can be recorded from the pro- and mesothoracic legs. Although Periplaneta is thought to be deaf and appears to ignore loud tones presented to the home colony, a more sensitive assay detects small leg movements in response to sound, confirming the presence of a functional auditory sense. The SGO is suspended from an expansion of the leg trachea, which may function to enhance sensitivity to vibration. This linkage preadapts the SGO to detect airborne sound transmitted in the tracheal system, and contact vibration may also stimulate the system in part by deforming the tracheae. It is proposed that auditory organs of crickets evolved from an ancestral SGO that already possessed dual responsiveness by subsequently developing effective vibration-isolating filters.

Journal Article↗
PubMed1994

Differential expression of integrins alpha 6 and alpha 4 determines pathways in human peripheral CD4+ T cell differentiation.

Integrins mediate leukocyte adhesion to vascular endothelium and thereby influence leukocyte recirculation. We have explored expression by peripheral blood T cells of beta 1 and beta 7 integrins, particularly alpha 4 beta 1 (VLA-4, CD49d), alpha 4 beta 7 (LPAM-1) and alpha 6 beta 1 (VLA-6, CD49f). Integrin expression differs between CD4+ cells and CD8+ cells in that CD4+ cells 1) are more heterogeneous, particularly for alpha 4; 2) express on the average less alpha 4 and beta 7; and 3) express on the average more alpha 6 and beta 1. 2D gel electrophoretic analysis was combined with flow cytometric analysis to determine which integrin chain pairs are expressed by the CD45RO- (naive) and CD45RO+ (memory) subsets of CD4+ cells. CD45RO- (naive) cells express homogeneously at intermediate levels the three integrin pairs alpha 6 beta 1, alpha 4 beta 1 and alpha 4 beta 7. Although 2D gel analysis suggests similar average integrin chain composition for CD45RO+CD4+ (memory) cells, flow cytometric analysis demonstrates multiple subsets of CD45RO+ cells differing markedly from each other and from naive cells in levels of expression of alpha 6 and alpha 4 integrins. There are a minimum of three CD45RO+ subsets: 1) alpha 4 beta 1hi alpha 6 beta 1hi alpha 4 beta 7neg, which comprises the majority of memory cells; 2) alpha 4 beta 7hi alpha 6 beta 1low presumptive gut-homing memory cells; and 3) alpha 6 beta 1hi alpha 4 beta 7neg alpha 4 beta 1neg, a previously unidentified subset expected to have unique migrational-functional properties. Of particular importance in these results are: the expression by CD4+ naive cells of alpha 6 beta 1, alpha 4 beta 1 and alpha 4 beta 7, the overall prominence and regulation of alpha 6 beta 1 on CD4+ cells, and the selective decreases as well as increases in alpha 4 beta 7 and alpha 4 beta 1 during CD4+ memory specialization. Taken together, these results suggest that differential regulation of expression of alpha 4 and alpha 6 integrin chains that accompany naive-to-memory transition in CD4+ cells are instrumental in generating functional subsets of CD4+ memory cells with specialized recirculation abilities.

CD4-Positive T-Lymphocytes↗
PubMed1994

Atrial natriuretic factor increases in response to an acute glucose load.

OBJECTIVE: To evaluate the effects of an acute glucose load on circulating atrial natriuretic factor (ANF) levels. METHODS: We investigated plasma ANF, glucose and insulin levels before and after intravenous administration of 50% D-glucose (300 mg/kg body weight) in healthy, normal volunteers. RESULTS: In study group A (n = 30) plasma ANF was found to be increased significantly 30 min after the glucose load. In study group B (n = 55) the response of plasma ANF over time was assessed. A peak plasma ANF response was observed 10 min after intravenous glucose loading; thereafter, plasma ANF levels returned gradually to basal levels at 50 min after glucose injection. The latter produced in both study groups a similar acute hyperglycaemia, and in group B the expected concomitant hyperinsulinaemia. CONCLUSION: These observations demonstrate that, in normal humans, acute marked hyperglycaemia is accompanied by a rapid increase in circulating ANF levels. In this metabolic interaction, ANF might counteract the renal sodium-retaining effect of acute hyperglycaemia and hyperinsulinaemia.

Adult↗