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Biomedical subjects

M Shalit

Publications and source records attributed to M Shalit.

At least 91 records · Page 5Linked to original sources
PubMed1987

Cellular inflammatory responses in human allergic skin reactions.

To define better the role of inflammation in the response to pollen antigens, we have used our skin chamber model to study inflammatory cells recovered from the sites of ongoing allergic reactions. In 15 atopic subjects, paired skin blister sites were simultaneously challenged with ragweed- or grass-pollen antigen or buffer for 5 hours. There were 10 times as many cells recovered at antigen (20.7 X 10(5)) than at buffer (2.0 X 10(5)) sites, p less than 0.005; greater than 97% of the cells recovered were neutrophils. The number of cells recovered at the antigen sites correlated with the total amount of histamine released (r = 0.57; p less than 0.05) but not with the extinction dilution skin test reactivity nor with the intensity of the late cutaneous allergic response measured 6 hours after the injection of antigen. Phase-contrast microscopic examination of the cells recovered from the antigen sites demonstrated that 82% to 95% were polarized compared to 0% to 1.5% of autologous blood neutrophils obtained simultaneously from the peripheral blood. Antigen site cells were as capable of serum-dependent phagocytosis as peripheral blood neutrophils. There was no significant difference in the migratory response to buffer, the chemoattractant N-formyl-methionyl-leucyl-phenylalanine, or leukotriene B4, but there was a significantly decreased response to platelet-activating factor when the cells recovered from antigen sites were compared to autologous blood neutrophils.(ABSTRACT TRUNCATED AT 250 WORDS)

Antigens↗
PubMed1987

Neutrophil activation in human inflammatory skin reactions.

To determine the functional activity of neutrophils emigrating to the sites of ongoing human allergic inflammatory reactions, we assessed the intensity of their intracellular oxidative metabolism by measuring the intracellular oxidation by H2O2 of the dye, 2',7'-dichlorofluorescein diacetate (DCFH-DA), to fluorescent 2',7'-dichlorofluorescein. The intensity of intracellular fluorescence was measured by flow cytometry. In 13 atopic subjects, two denuded skin blister bases were challenged for 5 hours with pollen antigen and two blister bases with buffer. Both the level of histamine and mean number of cells recovered at antigen sites were greater than at buffer sites. Oxidation of DCFH-DA by neutrophils recovered from both antigen and buffer sites was significantly greater than that of autologous peripheral blood neutrophils (PBNs), reflecting an increase in the spontaneous generation H2O2 of cells recovered from the sites of inflammation. DCFH-DA oxidation by cells recovered from sites of antigen incubation was significantly greater than cells from buffer site incubations. Neutrophils from both antigen and buffer sites could be stimulated further in vitro by phorbol myristate acetate to the same level of H2O2 generation as phorbol myristate acetate-stimulated PBNs. In five subjects studied, the noncellular component of chamber fluids collected at 1 and 5 hours stimulated PBNs to increase their oxidative metabolism by 42% to 62%; however, this increased level of intracellular H2O2 was still much less than the spontaneous H2O2 generation observed in cells recovered from sites of allergic inflammation. The increased oxidative metabolism of neutrophils in human allergic and inflammatory skin reactions has important pathophysiologic implications for the role of these cells in inflammatory responses.

Adult↗
PubMed1987

Release of tryptase together with histamine during the immediate cutaneous response to allergen.

Better in vivo techniques are needed for objective assessment of mast cell-dependent events. Tryptase, a neutral protease selectively concentrated in human mast cells, appears along with histamine in skin chamber fluid overlying sites of allergen challenge in sensitive human subjects. Maximal amounts of histamine were found 0 minutes to 30 minutes after challenge; maximal amounts of tryptase were found 30 minutes to 60 minutes after challenge. The later appearance of tryptase most likely reflects its slower diffusion through tissue after release of tryptase from cutaneous mast cells as a macromolecular complex with proteoglycan. The mean weight ratio of tryptase (134,000 molecular weight tetramer) to histamine (111 molecular weight) in chamber fluid after allergen challenge during a 1-hour time course was 4:1. Total amounts of tryptase and histamine recovered in the 0.3 ml chamber fluid samples after a 1-hour challenge averaged 95 ng and 26 ng, respectively. Tryptase levels in skin chamber fluid are an accurate indicator of mast cell activation.

Adolescent↗
PubMed1987

Bone marrow transplantation with T-cell-depleted grafts. II. Reconstitution of immunohemopoietic functions in lethally irradiated mice transplanted with unseparated or T-cell-depleted bone marrow grafts disparate at minor histocompatibility antigens.

Graft-versus-host disease (GVHD), a serious complication of allogeneic bone marrow transplantation (BMT), can be prevented by in vitro depletion of T cells from the bone marrow (BM) prior to transplantation. The purpose of this study was to assess the role of BMT cells in the reconstitution of various immune functions following BMT across minor histocompatibility barriers. Lethally irradiated CBA/J (H-2k) mice were grafted with either 10(7) unseparated or T-cell-depleted BM cells from B10.BR (H-2k, minor-histoincompatible) mice. Blood counts, BM colonies in agar, and various immune functions of spleen cells from the recipient mice were tested 2-12 weeks post-BMT and compared with those of normal donors. The following observations were made: (A) Peripheral blood lymphocyte counts decreased to 30% of normal 2 weeks post-BMT with almost normal recovery at 8 weeks. (B) The percentage of Thy1.2+ splenocytes reached normal levels at 8 weeks post-BMT. (C) The number of BM colonies (GM-CFU) was reduced to 10% at 2 weeks and fully recovered at 12 weeks. (D) Proliferative response to the B-cell mitogen LPS was fully reconstituted after 4 weeks; however, anti-SRBC PFC (following Mishell-Dutton cultures) was restored 50% at 8-12 weeks. (E) Reconstitution of T cell functions including proliferative responses to concanavalin A, phytohemagglutinin, and allogeneic leukocytes, and allocytotoxicity, did not exceed 50% even 12 weeks post-BMT. Overall, depletion of T cells from donor BM allografts incompatible at minor histocompatibility loci, did not seem to significantly alter the rate of immunohematopoietic reconstitution in the lethally irradiated BM recipients.

Animals↗
PubMed1987

Platelet-activating factor both stimulates and "primes" human polymorphonuclear leukocyte actin filament assembly.

The phospholipid inflammatory mediator, platelet-activating factor (PAF), can stimulate polymorphonuclear leukocyte (PMN) chemotaxis. Conversion of cytoplasmic actin from monomers to filaments is associated with PMN motile functions. Using the fluorescent actin filament stain nitrobenzodiaxole phallicidin, we have investigated PAF's effects on human PMN actin polymerization. Concentrations of PAF between 1 x 10(-11) to 1 x 10(-6) mol/L induced actin filament (F-actin) assembly. An optimal concentration of PAF (1-5 x 10(-8) mol/L) induced a significantly lower rise in relative F-actin content (1.72 +/- 0.07 SEM) than an optimal concentration (5 x 10(-7) mol/L) of the chemotactic peptide FMLP (2.21 +/- 0.06). Unlike FMLP (F-actin content: 1.25 +/- 0.04 at five seconds), PAF stimulation was associated with a delay of more than five seconds (1.04 +/- 0.01 at five seconds) before an increase in F-actin could be detected. F-actin concentration reached maximum levels by 30 to 60 seconds. Prolonged stimulation (20 minutes) with PAF was associated with two phases of polymerization and depolymerization. Like FMLP, the initiation of actin filament assembly by PAF required receptor occupancy, this reaction being totally blocked by the PAF receptor inhibitor, SKI 63-441. As evidenced by the lack of inhibition by nordihydroguaiaretic acid (5 to 20 mumol/L), the production of leukotriene B4 was not required for the PAF-induced changes in F-actin. Like FMLP, PAF's ability to stimulate PMN actin polymerization was inhibited by pertussis toxin (.05 to 2.5 micrograms/mL) but not impaired by the addition of EGTA and/or the calcium ionophore A23187. Preincubation with 1 x 10(-11) to 1 x 10(-8) mol/L PAF for 2 to 60 minutes enhanced the rise in F-actin content induced by low concentrations of FMLP (5 x 10(-12) to 1 x 10(-10) mol/L) indicating that this phospholipid was capable of "priming" the PMN actin polymerization response.

Actin Cytoskeleton↗
PubMed1987

Codeine-induced mast cell degranulation in human skin: effect of calcium channel blockers.

Codeine and other opiates can induce immediate type wheal and flare skin reactions. Calcium channel blockers including nifedipine have been shown to inhibit mast cell degranulation in different systems. The oral administration of nifedipine (10 mg) did not affect the size of codeine-induced skin reactions in ten normal volunteers. Mean wheal over flare sizes were 11.7 mm/29.2 mm before nifedipine and 11.5 mm/31.0 mm at peak nifedipine blood levels. Similar observations were made when codeine was injected locally with or without 20 micrograms nifedipine (12.1/29.2 mm and 13.2/29.2 mm, respectively). These data suggest that codeine-induced mast cell degranulation may be mediated by a calcium-independent mechanism. Alternatively, mast cells in the human skin may differ in their reactions to secretagogues when compared with basophils and mast cells from other human tissues or other species.

Adult↗
PubMed1986

New role for heparan sulfate: regulator of leukotriene generation in mouse E-mast cells.

In this work, bovine heparan sulfate, pig mucosa heparin and squid chondroitin sulfate-E glycosaminoglycans (GAGs) were compared as to their affect on the synthesis of leukotrienes C4 (LTC4) and B4 (LTB4) as well as on the production of prostaglandin D2 (PGD2) in cultured mouse E-mast cells (E-MC). The maximum percent increase in LTC4 generation in cells treated with 0.2 micrograms heparan sulfate was 52 +/- 3% (mean +/- S.E., n = 5). Whereas 0.5 micrograms of the GAG increased the production of LTB4 by 50% Ten micrograms of heparin slightly increased the LTC4 production (33%) whereas lower doses were found to be ineffective. No significant increase in LTC4 production was demonstrated when the IgE sensitized E-MC were treated with chondroitin sulfate-E GAG prior to the antigen challenge. Neither one of the three GAGs, at the various doses used, affected the antigen induced exocytosis of beta-hexosaminidase from the IgE sensitized E-MC. After 15 min preincubation with heparan sulfate, antigen induced release of PGD2 from 1 X 10(6) sensitized cells was inhibited from 5.4 ng +/- 0.1 ng into 3.5 ng +/- 0.1 ng at 0.5 micrograms/ml GAG. All of the three types of GAGs used were uneffective when the E-MC were activated by calcium ionophore A23187.

Animals↗
PubMed1986

Ventriculosubgaleal shunt: an effective CSF drainage in shunt disconnection.

A 4-year-old girl with a right ventriculoperitoneal shunt presented with a huge subcutaneous fluid collection in the scalp on the right side. There were no neurological symptoms or signs. On CT, a normal-sized ventricular system was seen. The shunt was disconnected distal to the antisiphon device and transmitted fluid into a subgaleal collection, which functioned as a reservoir for excess fluid. The ability of the subgaleal space to serve as a reservoir for cerebrospinal fluid is discussed.

Cerebrospinal Fluid Shunts↗
PubMed1986

Regulation of thrombin-induced mast cell degranulation by zinc and manganese.

This study was undertaken to determine whether zinc, manganese and copper could regulate the thrombin-induced secretion of the granule-associated mediator, beta-hexosaminidase, from mast cells derived from mouse bone marrow. Exposure of thrombin to copper (2-100 microM) does not affect the enzyme-induced release of beta-hexosaminidase from the mast cells. Zinc at 50 microM reduced the degranulation of calcium ionophore A23187 activated cells by 75% and that of immunological challenge or thrombin by 30% each. Exposure of the thrombin to incremental concentrations of manganese (2-100 microM) prevents its degranulation activity in a dose-related fashion. 75% inhibition of the enzyme activity was achieved at 100 microM manganese. However, exposure of IgE sensitized or unsensitized cells to incremental concentrations of manganese (2-400 microM) prior to antigen or calcium ionophore A23187 stimulation, does not significantly affect the exocytosis of beta-hexosaminidase. The binding of purified human FITC-thrombin to E-mast cells was analyzed by fluorescence flow cytometry. All cells bound specifically the labelled thrombin. Pretreatment of the FITC-thrombin with 100 micron zinc or manganese had no effect on the binding of the labelled thrombin to the cells. It was assumed that manganese modulates either directly the thrombin activity or the substrate for the enzyme on the cell surface.

Animals↗
PubMed1986

Combined cyclophosphamide and corticosteroid-induced remission in severe glomerulopathy associated with systemic vasculitis.

Three patients with systemic vasculitis and severe renal disease as major manifestations are reported. In 2 cases, rapidly progressive glomerulonephritis presented as oliguric renal failure. In the third case, the clinical picture was severe nephrotic syndrome with decreased renal function. Combined cyclophosphamide and corticosteroid treatment resulted in dramatic improvement of renal function and remission of nephrotic syndrome. In 2 cases, histological improvement was documented by repeated kidney biopsy. The optimal duration of cyclophosphamide therapy has to be determined.

Adult↗
PubMed1986

Bone marrow transplantation with T-cell-depleted grafts. I. Reconstitution of immunohemopoietic functions in lethally irradiated mice transplanted with unseparated or T-cell-depleted syngeneic bone marrow grafts.

The potential role of donor's mature T lymphocytes on the recovery of various immunological functions and hematopoiesis was investigated in lethally irradiated BALB/c mice by studying reconstitution with normal, as compared with T-cell-depleted, syngeneic marrow grafts. Recovery of total, as well as mononuclear, peripheral white blood cell counts, platelets, hemoglobin levels, proportion of Thy 1.2+ cells, responses to concanavalin A, phytohemagglutinin and lipopolysaccharide, mixed lymphocyte response, cell-mediated lympholysis response, anti-SRBC agglutinins and natural killer activity were basically similar in recipients of unmanipulated (as compared with T cell depleted) syngeneic marrow grafts. The data suggest that in a syngeneic murine bone marrow transplantation setting, mature donor T lymphocytes do not seem to play a major role in immunohemopoiesis. Normal T cell number and T-cell-dependent immune function can be readily regenerated out of the stem cell reservoir of adult donors following transplantation into lethally ablated recipients.

Animals↗
PubMed1986

Tumor genesis syndrome. Hypophosphatemia accompanying Burkitt's lymphoma cell leukemia.

A case of Burkitt's lymphoma cell leukemia with recurrent hypophosphatemia that coincided with tumor growth, and hyperphosphatemia during tumor lysis is presented. Redistribution of body phosphorus with increased uptake by the rapidly replicating tumor cells is suggested. Tumor genesis syndrome seems to us to be a proper term to include metabolic abnormalities that result directly from tumor growth.

Adult↗
PubMed1986

Serum IgE levels in patients with inflammatory bowel disease.

The role of allergy in the pathogenesis of inflammatory bowel disease (IBD) is unclear. The present study was performed to evaluate serum levels of IgE and other immunoglobulin classes in patients with IBD. Patients with IBD had significantly elevated serum levels of both IgG and IgM in the presence of normal levels of IgA. Serum concentration of IgE, as well as the prevalence of patients with "high IgE" were significantly increased in IBD. Among patients with IBD, those with Crohn's disease or those in relapse had the highest levels of IgE. The possibility that allergy plays a pathogenic role in a subset of IBD is discussed.

Adolescent↗
PubMed1985

Serum amyloid P-component as a marker of liver involvement in measles infection.

The P-component of amyloid (SAP) is a normal serum protein. Recent studies have pointed to the liver as the site of synthesis of SAP. Moreover, we have recently demonstrated a close correlation between serum level of SAP and the degree of liver impairment in patients with acute hepatitis, chronic active hepatitis, and cirrhosis. In the present study we have investigated liver involvement and serum SAP level during measles infection. Up to 80% of patients with measles had evidence of hepatic dysfunction. Serum SAP level was markedly decreased in patients with measles and correlated with the presence of liver involvement. Taken together, this finding suggests that serum SAP level might be a useful and sensitive indicator of liver disease.

Adolescent↗