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Biomedical subjects

J Braunstein

Publications and source records attributed to J Braunstein.

At least 19 recordsLinked to original sources
PubMed2002

Signaling through the JAK/STAT pathway, recent advances and future challenges.

Investigation into the mechanism of cytokine signaling led to the discovery of the JAK/STAT pathway. Following the binding of cytokines to their cognate receptor, signal transducers and activators of transcription (STATs) are activated by members of the janus activated kinase (JAK) family of tyrosine kinases. Once activated, they dimerize and translocate to the nucleus and modulate the expression of target genes. During the past several years significant progress has been made in the characterization of the JAK/STAT signaling cascade, including the identification of multiple STATs and regulatory proteins. Seven STATs have been identified in mammals. The vital role these STATs play in the biological response to cytokines has been demonstrated through the generation of murine 'knockout' models. These mice will be invaluable in carefully elucidating the role STATs play in regulating the host response to various stresses. Similarly, the solution of the crystal structure of two STATs has and will continue to facilitate our understanding of how STATs function. This review will highlight these exciting developments in JAK/STAT signaling.

Animals↗
PubMed2000

Thiol-mediated redox regulation of intestinal lamina propria T lymphocytes.

Intestinal lamina propria T lymphocytes (LP-Ts) have a markedly low proliferative potential both in vivo and in vitro. Here, we have identified that the capacity of antigen-presenting cells to release cysteine upon receptor-ligand interactions represents a critical parameter for proliferation of LP-Ts. The availability of cysteine is limiting for the intracellular production of glutathione, which in turn is essential for cell cycle progression. When cysteine is provided either directly or by addition of the reducing agent 2-mercaptoethanol to cystine-containing culture medium, proliferation of LP-T is fully restored. Importantly, coculture with peripheral blood monocytes that easily take up cystine, reduce cystine, and secrete cysteine also restores reactivity of LP-Ts to T cell receptor/CD3 stimulation. In marked contrast, lamina propria macrophages lack this capacity to elaborate cysteine, and thereby secure physiological unresponsiveness to antigen exposure in the intestinal microenvironment. The well-documented local recruitment of blood monocytes in inflammatory bowel disease (IBD) may thus represent an important parameter underlying hyperresponsiveness of T cells, an essential component of the pathogenesis of IBD.

Antigen-Presenting Cells↗
PubMed1998

In situ expression of interleukin-10 in noninflamed human gut and in inflammatory bowel disease.

A dysregulated secretion of contra-inflammatory cytokines such as interleukin-10 (IL-10) could play a role in the pathogenesis of inflammatory bowel disease (IBD). We have investigated the expression of IL-10 in gut tissues from patients with Crohn's disease (CD), ulcerative colitis (UC) and controls by mRNA in situ hybridization and immunohistochemistry. Intestinal epithelial cells were found to express IL-10 mRNA and IL-10 protein in all of the tissues investigated without any major differences in the expression patterns. However, compared with noninflamed gut, significantly increased numbers of mononuclear cells (MNCs) producing IL-10 were present in inflamed gut, both in CD and UC. This cytokine was expressed most prominently by inflammatory infiltrates enriched in macrophages, although T cells seem to contribute to its production as well. Elevated IL-10 expression in IBD was mainly detected in the submucosa, whereas IL-10 production by lamina propria cells remained comparably low. In contrast, the expression of IL-1beta mRNA was preferentially increased in the lamina propria. Our data argue against a general deficiency in IL-10 production in IBD. The results suggest rather that the local production of IL-10 by mucosal MNCs in IBD is insufficient to down-regulate pro-inflammatory cytokines such as IL-1beta in the lamina propria compartment.

Adult↗
PubMed1997

T cells of the human intestinal lamina propria are high producers of interleukin-10.

BACKGROUND AND AIM: Some of the recently observed functional features characteristic of immunocompetent cells residing in the human intestinal lamina propria could be mediated by interleukin-10 (IL-10). To investigate the role of IL-10 in the human intestinal mucosa, the regulation of IL-10 production by lamina propria T lymphocytes (LPL-T) was determined and compared with that of peripheral blood T lymphocytes (PBL-T). METHODS: Following activation by using different stimuli, IL-10 release by LPL-T and PBL-T into the supernatant was measured by enzyme linked immunosorbent assay (ELISA). In parallel, cell growth was determined by [3H]-thymidine incorporation. RESULTS: Neither LPL-T nor PBL-T release IL-10 constitutively. Triggering through CD2 or the T cell receptor (TCR)/CD3 complex in the presence of autologous monocytes induces significantly greater IL-10 secretion by LPL-T than by PBL-T. Engagement of the CD45 receptor enhances IL-10 release and proliferation of CD2 triggered CD45RO+ PBL-T. In contrast, it reduces CD2 induced IL-10 production by LPL-T without altering cell growth significantly. CONCLUSIONS: Activated LPL-T release relatively high amounts of IL-10. Enhanced IL-10 production by activated LPL-T, in comparison with activated PBL-T, is not only related to the presence of a higher proportion of CD45RO+ T cells in the intestinal lamina propria, but is also caused by increased sensitivity of LPL-T to CD2 co-stimulation. The differential responsiveness of LPL-T, compared with PBL-T, to CD45 engagement demonstrates that CD45 could be involved in the altered CD2 reactivity of LPL-T.

Blood↗
PubMed1996

Differential regulation of human T cell responsiveness by mucosal versus blood monocytes.

Human intestinal T lymphocytes are constantly exposed to a large number of foreign antigens without developing a systemic immune response. One crucial mechanisms leading to this intestinal hyporesponsiveness is based on impaired signal transduction through the T cell receptor/CD3 complex in lamina propria T lymphocytes (LP-T). In this study, we addressed the question whether a lack of co-stimulatory/progression signals might also contribute to LP-T hyporesponsiveness. To this end, isolated human monocyte populations from the intestinal lamina propria were obtained and their phenotypes as well as their capacity to promote T cell activation studied. Here, we demonstrate that lamina propria macrophages (LP-MO), in contrast to peripheral blood monocytes (PB-MO), do not support proliferation of either LP-T or PB-T. This may be due to the low expression of ligands (CD54, CD58, CD80) for the T cell accessory receptors CD11/18, CD2 and CD28/CTLA-4 on mucosal macrophages. Thus, down-regulation of both recognition/competence and co-stimulatory/progression signals contribute to intestinal hypo- or unresponsiveness.

Antigens↗
PubMed1996

Detection of a soluble form of the human adhesion receptor lymphocyte function-associated antigen-3 (LFA-3) in patients with chronic liver disease.

BACKGROUND/AIMS: Multiple immune functions, such as cytotoxic reactions, B cell differentiation, and monocyte activation, are mediated via the adhesion receptor/ligand pairs CD2/lymphocyte function-associated antigen(LFA)-3 and LFA-1/ intercellular adhesion molecule(ICAM)-1. Since soluble forms of LFA-3 (sLFA-3) and ICAM-1 (sICAM-1) can interfere with these functions, we asked whether increased levels of sLFA-3 can be found in patients with different forms of chronic liver disease and/or hepatocellular carcinoma. METHODS: sLFA-3 was measured in sera from 84 patients with chronic liver disease (39 with chronic viral liver disease, 30 with autoimmune liver disease, 12 with alcoholic cirrhosis, 3 with other causes of cirrhosis), 24 patients with hepatocellular carcinoma (15 with and 9 without cirrhosis), and 61 normal controls. From 36 of the patients with liver cirrhosis, arterial and hepatic venous serum samples were simultaneously obtained and tested for sLFA-3 and sICAM-1. RESULTS: In comparison to controls, sLFA-3 levels were elevated in patients with liver cirrhosis due to autoimmune liver disease (p < 0.0001) and viral liver disease (p = 0.001), but not in patients with alcoholic cirrhosis. Increased sLFA-3 levels were also found in patients with hepatocellular carcinoma and liver cirrhosis. However, sLFA-3 was not significantly elevated in sera from patients with autoimmune liver disease, viral liver disease, and hepatocellular carcinoma without concomitant liver cirrhosis. No difference was found between arterial and hepatic venous serum levels of sLFA-3 and sICAM-1. sLFA-3 levels correlated positively with aspartate transaminase, alkaline phosphatase, bilirubin, sICAM-1, and inversely with albumin and cholinesterase. CONCLUSIONS: Taken together, sLFA-3 serum concentrations of patients with liver cirrhosis due to autoimmune liver disease or viral liver disease and of patients with hepatocellular carcinoma and cirrhosis are significantly increased compared to controls. Elevated sLFA-3 and sICAM-1 levels might reflect the generalized inflammation in cirrhosis and by interference with cell-cell interactions sICAM-1 and sLFA-3 may limit the extent of inflammation.

Adult↗
PubMed1992

Negative predictive value of a population-based preschool vision screening program.

BACKGROUND: The Enhanced Vision Screening Program is a population-based vision screening program that has, at present, examined 59,782 children. Its main goal is to detect amblyopia, strabismus, and high refractive errors. An average of 11,910 4 1/2- to 5 1/2-year-old children are screened yearly. The current study determines the negative predictive value of the screening program: For a subject having passed the vision screening test, what is the probability of not having amblyopia, strabismus, or high refractive errors? METHODS: Of the 11,734 subjects who passed the vision screening, 200 were randomly chosen to undergo a strictly defined gold standard examination by an orthoptist and an ophthalmologist. RESULTS: Of the 200 randomly chosen subjects, 157 underwent the gold standard evaluation. The negative predictive value of the Enhanced Vision Screening Program was 97.6% for any potentially vision-threatening ocular condition. It was 98.7% if we considered only the visually significant ocular problems that the test was designed to detect. CONCLUSION: Because the negative predictive value of the Enhanced Vision Screening Program is not 100%, some children with amblyopia, strabismus, or refractive errors are missed. Occasionally, a rare, potentially vision-threatening condition may go undetected. Parents should be made aware of this when they receive the results of the vision screening.

Child↗
PubMed1988

Condylomata acuminata of the urinary bladder. Natural history, viral typing, and DNA content.

Three patients with condylomata acuminata of the urinary bladder are reported. Two of the patients were immunosuppressed, and one had longstanding extensive condylomata acuminata of the external genitalia and adjacent areas. All lesions recurred at least once and were difficult to treat. The diagnosis was confirmed by in situ hybridization on archival material with human papillomavirus (HPV) DNA probes under stringent conditions. In two of the patients, probes for HPV types 6 and 11 were positive; HPV 11 only was identified in one patient. Probes for HPV types 16 and 18 and pBR322 vector controls were negative. In one patient with a strong hybridization signal, the lesion was also positive for common papillomavirus antigen. DNA content measured by cytophotometry of Feulgen-stained whole nuclei isolated from lesions in two patients revealed a markedly aneuploid DNA pattern. Whether this is a factor in the behavior of the lesions is not known at this time. Although rare, HPV infection of the urinary bladder may result in widespread condylomatosis and may mimic giant condylomas of Buschke-Löwenstein or even verrucous carcinomas, sometimes necessitating radical treatment. Nevertheless, until there is proof to the contrary, the lesions must be considered benign and should not be confused with squamous cancer of the bladder.

Adult↗
PubMed1987

Parental perception of urgency and utilization of pediatric emergency services.

Emergency Room utilization has increased dramatically in recent years. Parental perception of urgency may be one factor that influences utilization of pediatric emergency services, yet little is understood about factors influencing this perception. The goal of this study was to determine if the perception of urgency is a critical factor in the decision of a parent to seek care in an emergency room, if demographic and access factors influence parental perception of urgency, and whether there is agreement of urgency rating by parent and physician. One hundred and one parents were interviewed to determine background demographic and access factors and perception of urgency. Physician and parental urgency was evaluated on a 5 level scale. Chi-square analysis was used to determine association between demographic and access factors and parental urgency ratings. Pearson product moment correlation was used to determine agreement between parent and physician urgency ratings. The majority of visits were acknowledged by both parents and physicians to be non-emergent. Fourteen (13.9%) and 10 (9.9%) of parents and physicians rated the visits as emergent (levels 1 and 2) while 65 (64.4%) parents and 76 (75.3%) physicians rated the visits as nonemergent. No association between demographic or access variables and parental perception of urgency was demonstrated.

Adult↗