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M Bigby

Publications and source records attributed to M Bigby.

At least 55 records · Page 3Linked to original sources
PubMed1993

Most gamma delta T cells develop normally in the absence of MHC class II molecules.

MHC class I and class II molecules are essential for intrathymic maturation of a normal repertoire of alpha beta T cells. The development of gamma delta T cells may similarly require exposure to conventional MHC or MHC-like molecules for appropriate negative and positive selection. The availability of mice that are devoid of cell surface expression of MHC class II molecules allowed us to test directly the hypothesis that conventional class II molecules play a role in the development of gamma delta T cells. The proportions of gamma delta cells in thymus, lymph nodes, and spleens were indistinguishable between class II-deficient mice and littermate controls by FACS analysis. gamma delta T cells from class II-deficient mice proliferated normally in response to anti-TCR mAb. Examination of epidermal sheets from ear, torso, and tail skin demonstrated that class II-deficient mice had the same population density and distribution of gamma delta+ dendritic epidermal T cells as that of control littermates. gamma delta Cells in the epidermis of class II-deficient mice expressed Thy-1 and CD3 and were predominantly V gamma 3+. There were no significant differences in the immunophenotype of class II-deficient mice and their normal littermates in two-color immunofluorescence analysis of intestinal intraepithelial lymphocytes. Class II-deficient mice and control mice had 29 to 39% gamma delta bearing intestinal intraepithelial lymphocytes, of which 16 to 21% expressed V delta 4. Dendritic cells that stained positively for Thy-1, CD3, and gamma delta were identified in the vaginal epithelium of class II-deficient mice and their normal littermates. Our results indicate that MHC class II expression is not essential for the development of most gamma delta T cells.

Animals↗
PubMed1993

T-cell receptor V beta expression in normal human skin.

The skin-associated immune system is the first line of defense against pathogenic attack from the environment and is simultaneously tolerant to localized autoantigens and to antigens of the normal microbial flora. The T-cell receptor (TCR) repertoire of skin lymphocytes may therefore be influenced by the skin microenvironment. We studied the expression of TCR beta-chain variable region (V beta) genes in normal skin by a polymerase chain reaction-based comparative method. When comparing the amplification of V beta genes in peripheral blood and normal skin, we found that TCR V beta 1, -7, -14, and -16 were often highly expressed in skin relative to peripheral blood, whereas V beta 5.1 was often highly expressed in peripheral blood mononuclear cells but not in skin. These results demonstrate that the TCR repertoire of skin lymphocytes is not determined by random sampling of peripheral blood mononuclear cells but may be molded by the interaction with self antigens and/or the normal microbial flora in the microenvironment of the skin.

Base Sequence↗
PubMed1993

Monoclonal anti-CD44 antibody acts in synergy with anti-CD2 but inhibits anti-CD3 or T cell receptor-mediated signaling in murine T cell hybridomas.

We investigated the effects of anti-murine CD44 monoclonal antibodies on the activation of antigen-specific T cell hybridomas. Anti-murine CD44 antibodies by themselves did not induce the production of IL-2 by antigen-specific T cell hybridomas. However, anti-murine CD44 monoclonal antibodies were able to either inhibit or enhance the production of IL-2, depending on the other monoclonal antibodies used as comitogenic stimuli. When a T cell hybridoma was activated by antigen and antigen-presenting cells or anti-CD3 antibodies, addition of anti-CD44 antibodies inhibited IL-2 production. In contrast, monoclonal anti-CD44 antibodies acted in synergy with anti-human CD2 antibodies in stimulating a murine T cell hybridoma stably transfected with the human CD2 gene to produce IL-2. Therefore, cross-linking of surface CD44 is able to deliver either a positive or a negative signal in murine antigen-specific T cell hybridomas. One of the ligands for CD44 is hyaluronic acid. Hyaluronic acid in vitro significantly increased the activation of murine T cell hybridomas. Hyaluronic acid itself was mitogenic for T cell hybridomas. Therefore, in addition to being an adhesion molecule, CD44 functions as a signal-transducing molecule on murine T cell hybridomas.

Animals↗
PubMed1990

Phorbol myristate acetate-induced down-modulation of CD4 is dependent on calmodulin and intracellular calcium.

PMA causes rapid down-modulation of CD4 molecules on murine immature thymocytes, human PBL, and CD4-positive human tumor cell lines, but not on murine peripheral lymphocytes. The mechanisms of phorbol ester-induced down modulation of CD4 molecules, however, have not been elucidated. To determine how PMA down-modulates CD4 expression by T lymphocytes, we studied the ability of inhibitors of protein kinase C, calmodulin, actin, and tubulin to block PMA-induced modulation of CD4 in several murine and human cell types. We also tested the ability of intracellular and extracellular calcium chelators to block CD4 internalization. There was marked variability in the degree of PMA-induced down-modulation of CD4 among various cell types. The effects of PMA on CD4 expression were greater for murine thymocytes, for human PBL, and for the human lymphoblastic leukemia cell line, MOLT-3, than for any of the other cell types studied. The protein kinase C inhibitor, 1-(5-isoquinolinesulfonyl)-2-methylpiperazine, blocked phosphorylation but not internalization of CD4 molecules induced by PMA. Therefore, phosphorylation of CD4 molecules by protein kinase C is not required for the internalization of the molecules. Internalization was blocked by both inhibitors of calmodulin, N-(6-aminohexyl)-5-chloro-1-naphthalene-sulfonamide, and trifluoperazine. PMA-induced internalization of CD4 was blocked by Quin-2 AM, which chelates intracellular calcium. EGTA, which chelates extracellular calcium, did not block internalization. Inhibitors of actin or tubulin did not block internalization. These results suggest that PMA-induced modulation of CD4 can occur in the absence of phosphorylation of the CD4 molecules and is calmodulin and intracellular calcium dependent.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1990

Urticaria: clinical efficacy of cetirizine in comparison with hydroxyzine and placebo.

Chronic urticaria is a problem for both physician and patient. In an effort to avoid the risks associated with corticosteroid treatment, many first-generation H1-receptor antagonists have been tried and found to induce undesirable levels of sedation when given in amounts sufficient to control urticaria. Cetirizine, a pharmacologically active oxidized metabolite of hydroxyzine, was developed to provide selective H1-receptor inhibition without depression of the central nervous system. In a 4-week, multicenter, double-blind, placebo-controlled safety and efficacy study, cetirizine, in a once-a-day dose (5 to 20 mg), was equivalent in efficacy to hydroxyzine in divided doses (25 to 75 mg/day). The incidence of somnolence in the cetirizine group was not significantly different from that of the placebo group. However, in the hydroxyzine group, the incidence of somnolence was significantly higher than that in the placebo group (p = 0.001). The results of this study demonstrate that cetirizine has a greater safety margin over the older parent drug hydroxyzine.

Adolescent↗
PubMed1989

Production of hapten-specific T cell hybridomas and their use to study the effect of ultraviolet B irradiation on the development of contact hypersensitivity.

We produced a series of T cell hybridomas that produce IL-2 when cultured with syngeneic APC coupled to FITC or TNP. These hybridomas are hapten specific and Ia restricted. The hybridomas were used to detect hapten-bearing APC in draining lymph nodes of mice sensitized with trinitrochlorobenzene or FITC in vivo. Hapten-bearing APC capable of stimulating the hybridomas were detectable in draining lymph nodes of hapten-painted mice within 3 h after sensitization. The ability of lymph node APC to stimulate the hybridomas peaked at 24 h and declined by 48 h. The dendritic cell subpopulation was the subpopulation of cells that were found in the regional lymph nodes of hapten-painted animals that were capable of stimulating the hybridomas to produce IL-2. Prior treatment of the skin with low dose UVB irradiation before epicutaneous application of contact sensitizers significantly reduced the capacity of hapten-bearing APC to stimulate the hybridomas. This observation was corroborated by results obtained from flow microfluorometry analysis of lymph node cells from FITC-sensitized mice. Lymph node dendritic cells obtained from FITC-painted mice contain a brightly staining group of cells by flow microfluorometry analysis. Lymph node dendritic cells from FITC-painted, UVB-irradiated mice did not contain this brightly staining population. These results indicate that low dose, local UVB irradiation may affect APC migration and/or function. We believe that these hybridomas will prove to be useful tools in the study of the development and regulation of contact hypersensitivity.

Animals↗
PubMed1989

Requirements for modulation of the CD4 molecule in response to phorbol myristate acetate. Role of the cytoplasmic domain.

CD4 (T4) is a 60 kD glycoprotein expressed on a subset of T lymphocytes. CD4 augments T cell responses to suboptimal Ag stimulation. In addition, the CD4 molecule is the receptor for HIV-1. CD4 is phosphorylated on serine residues within the cytoplasmic domain and its cell surface expression is decreased in response to PMA, APC bearing the appropriate Ag or HIV infection. The kinetics of CD4 phosphorylation and modulation are similar, suggesting that the two events may be related. L3T4, the murine CD4 equivalent, is not modulated from the surface of mature, peripheral T cells in response to PMA. The difference in the ability to modulate L3T4 and CD4 in response to PMA may be due to differences between the two molecules or to differences between the cells in which they are expressed. To further define the requirements for CD4 modulation, we used retroviral vectors to transfer the cDNA for CD4 and various mutants of CD4 into two murine T cell hybridomas that express L3T4. One of these hybridomas, By155.16, does not modulate L3T4 in response to PMA and the other, 5D5.63, does modulate L3T4 in response to PMA. When expressed by these hybridomas CD4 is not modulated from the surface of By155.16 and is modulated from the surface of 5D5.63 in response to PMA. In both of these hybridomas, CD4 is phosphorylated on serine residues in response to PMA. A mutant form of CD4, CD4 delta, was constructed in which the majority of the cytoplasmic domain was deleted. When expressed in 5D5.63, CD4 delta was not modulated in response to PMA. Replacing the cytoplasmic domain of CD4 with that of the human IL-2 receptor did not reconstitute the ability of CD4 to be modulated. These results suggest that the inability to modulate L3T4 from the surface of murine peripheral T cells is due to features of the cell and not the molecule. Furthermore, the cytoplasmic domain of CD4 is required for its modulation from the cell surface in response to PMA.

Amino Acid Sequence↗
PubMed1989

Allergic cutaneous reactions to drugs.

Because the pathophysiology of many drug eruptions is unknown, the presumption that a drug eruption is due to immune mechanisms is often based on clinical features. The drug exanthem, urticaria, and contact dermatitis are the most common adverse cutaneous reactions to medications. Drug exanthems occur in 2 to 3 per cent of medical inpatients and are most commonly caused by antibiotics and blood products. The incidence of drug exanthems is much higher in certain patient populations (for example, patients with AIDS treated with trimethoprim-sulfamethoxazole). Urticaria is the second most common allergic cutaneous reaction to drugs. Individual urticarial lesions last for less than 24 hours and do not leave hyperpigmentation or scarring. Urticaria not accompanied by systemic symptoms should not be treated with systemic corticosteroids or parenteral epinephrine. Allergic contact dermatitis is commonly caused by neomycin, benzocaine, ethylenediamine, diphenhydramine, and transdermal patches. The clinical spectrum of other, less common drug eruptions is wide. Toxic epidermal necrolysis, erythema multiforme, and fixed drug eruptions share similar pathologic features, are caused by many of the same drugs, and may have a similar pathogenesis. Photoallergic drug reactions require the interaction of drugs, UV irradiation, and the immune system. Drugs implicated in causing photoallergy include thiazide diuretics, sulfonamides, and phenothiazines. Eruptions seen in serum sickness include the drug exanthem, urticaria, vasculitis, urticarial vasculitis, and erythema multiforme. Identifying and discontinuing the responsible drug is usually essential for successful therapy of drug eruptions.

Drug Eruptions↗
PubMed1988

Adverse reactions to isotretinoin. A report from the Adverse Drug Reaction Reporting System.

Between October 1982 and June 1985 the Adverse Drug Reaction Reporting System received reports of 104 suspected adverse reactions occurring in 93 patients who took isotretinoin. Adverse reactions involving the skin and mucous membranes (29 reports), central nervous system (23), musculoskeletal system (12), pregnancy (11), and eyes (8) were most commonly reported. Severe headache was the most frequently reported adverse reaction (15 reports). In four cases headaches were attributed to pseudotumor cerebri. Some of the reported reactions, for example, a disulfiram (Antabuse)-like reaction and oculogyric crisis, have not been described previously in the literature. Other reports, such as congenital malformations, serve to emphasize some of the serious reactions that are known to occur. These spontaneous reports of adverse reactions associated with isotretinoin use, together with the literature we review, may help alert physicians to the diverse spectrum of adverse reactions that may develop in patients taking isotretinoin.

Abnormalities, Drug-Induced↗
PubMed1987

Selective down modulation of L3T4 molecules on murine thymocytes by the tumor promoter, phorbol 12-myristate 13-acetate.

Treatment of murine thymocytes, but not mature peripheral T cells, with the tumor promoter, phorbol 12-myristate 13-acetate (PMA), 3 results in a rapid disappearance of L3T4 molecules from the surface of thymocytes. The effect of PMA on L3T4 molecules persists in vitro for at least 72 hr. Down modulation of L3T4 molecules was PMA dose-dependent and temperature-dependent. L3T4 molecules on cortisone-resistant thymocytes were significantly less sensitive to the effect of PMA than were L3T4 molecules on cortisone-sensitive thymocytes. Down modulation of L3T4 molecules on thymocytes did not interfere with their capacity to respond to concanavalin A or activation signals delivered via their T cell receptors. The difference in the ability of thymocytes and peripheral T cells to respond to PMA cannot be explained by differences in the number of PMA receptors. Both thymocytes and peripheral T cells have PMA receptors in the range of 1 to 1.5 X 10(5) receptors/cell. However, there is a small difference in the affinity (Kd) of the receptors on thymocytes (Kd = 30 to 40 nM) and peripheral T cells (Kd = 10 to 15 nM). Immunofluorescent staining revealed that the down modulation of L3T4 molecules by PMA was a result of internalization of L3T4 molecules. After down modulation, L3T4 could be readily detected on the cytoplasm of thymocytes. These findings suggest that L3T4 molecules on thymocytes may be subject to different regulatory signals than L3T4 molecules on peripheral T cells.

Animals↗
PubMed1987

Ratio of Langerhans cells to Thy-1+ dendritic epidermal cells in murine epidermis influences the intensity of contact hypersensitivity.

We have initiated a series of studies in vivo to investigate the physiologic role of Langerhans cells and Thy-1+ dendritic epidermal cells in the development and regulation of contact hypersensitivity. The density of I-A+ Langerhans cells and Thy-1+ dendritic epidermal cells in ammonium thiocyanate-separated epidermal sheets was determined in ten strains of inbred mice using immunofluorescence microscopy with monoclonal anti-I-A and anti-Thy-1 antibodies. Mice of different inbred strains were sensitized by painting the left ear with varying doses of either oxazolone or trinitrochlorobenzene. From five to 20 days after sensitization, groups of mice were challenged with the relevant antigen and the intensity of contact hypersensitivity, as measured by ear swelling, was determined. We then determined whether the intensity and/or duration of contact hypersensitivity in different strains of mice was influenced by the density of Thy-1+ dendritic epidermal cells or the ratio of I-A+ Langerhans cells to Thy-1+ dendritic epidermal cells. We found that there was marked variability in the density of Thy-1+ dendritic epidermal cells and I-A+ Langerhans cells in the ten strains of mice studied. The ratio of I-A+ Langerhans cells to Thy-1+ dendritic epidermal cells ranged from 0.5 in C57BL/10J mice to greater than 22 in A/J and BALB/cByJ mice. When small amounts of contact sensitizers were used to induce contact hypersensitivity (e.g., 20 micrograms of oxazolone or trinitrochlorobenzene), there was consistent strain variability in the intensity of ear swelling. There was a significant correlation between the ratio of I-A+ Langerhans cells to Thy-1+ dendritic epidermal cells and the intensity of contact hypersensitivity (Pearson's correlation coefficient 0.85, p = 0.002). Strains with the highest ratios of I-A+ Langerhans cells to Thy-1+ dendritic epidermal cells had the most ear swelling. There were no consistent differences in the duration of contact hypersensitivity observed among the ten different strains. Our results indicate that Thy-1+ dendritic epidermal cells may play a physiologic role in down-regulating contact hypersensitivity in vivo.

Animals↗
PubMed1986

Drug-induced cutaneous reactions. A report from the Boston Collaborative Drug Surveillance Program on 15,438 consecutive inpatients, 1975 to 1982.

We analyzed the data on 15,438 consecutive medical inpatients monitored by the Boston Collaborative Drug Surveillance Program from June 1975 to June 1982 to determine the rates of allergic cutaneous reactions to drugs introduced since 1975 and to confirm and extend findings from an earlier study of the preceding 22,227 patients. There were 358 reactions occurring in 347 patients, for an overall reaction rate among patients of 2.2%. Each patient received a mean of eight different drugs. Rashes were attributed to 51 drugs, and 75% of the allergic cutaneous reactions were attributed to antibiotics, blood products, and inhaled mucolytics. Amoxicillin (51.4 reactions per 1000 patients exposed), trimethoprim-sulfamethoxazole (33.8/1000), and ampicillin (33.2/1000) had the highest reaction rates. Drug-specific reaction rates ranged from zero to 51.4 per 1000 and were determined for 180 drugs or drug groups. These results provide physicians with quantitative data that will be helpful in clinical decision making when drug-induced exanthems, urticaria, or generalized pruritus occurs.

Anti-Bacterial Agents↗
PubMed1985

Cutaneous reactions to nonsteroidal anti-inflammatory drugs. A review.

The nonsteroidal anti-inflammatory drugs are one of the most commonly prescribed classes of drugs used in medical practice. This review discusses the diverse cutaneous reactions associated with nonsteroidal anti-inflammatory drugs. Adverse cutaneous reactions occur most frequently with benoxaprofen, piroxicam, sulindac, meclofenamate sodium, zomepirac sodium, and phenylbutazone. The most serious adverse cutaneous reactions, Stevens-Johnson syndrome and toxic epidermal necrolysis, appear to be most often associated with sulindac and phenylbutazone. Tolmetin and zomepirac sodium, two structurally similar pyrrole derivatives, have been associated with a disproportionate number of cases of anaphylactoid reactions. Among the currently marketed nonsteroidal anti-inflammatory drugs, piroxicam appears to have the highest rate of phototoxic reactions. This phototoxic eruption is most often vesiculobullous.

Acetates↗