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Biomedical subjects

S M Fikrig

Publications and source records attributed to S M Fikrig.

At least 19 recordsLinked to original sources

Modification of neutrophil functions by naftifine.

Naftifine (NF), a topical antimycotic agent, is highly active in vitro and in vivo against a wide range of pathogenic fungi. NF inhibits human polymorphonuclear leucocyte (PMN) chemotaxis. Following stimulation with zymosan-activated serum, 85-97% of the PMNs exhibited detectable membrane ruffling and polarity. In contrast, NF-treated PMNs did not exhibit such chemotactic factor-induced shape changes. We also analysed the effect of NF on PMN superoxide anion (O2-) and chemiluminescence (CL) production, as a measure of respiratory burst activity. Stimulation of PMNs pre-incubated with NF (37 degrees C for 30 min at 1-150 micrograms/ml) by FMLP, PMA and zymosan resulted in a dose-dependent inhibition in PMN CL. Doses of NF which depressed chemotaxis, inhibited CL and diminished O2- production in a statistically significant manner (P < 0.05-0.001). In conclusion, NF alters membrane-related responses in PMNs, and this alteration may be associated with a change in PMN morphology. Binding of NF to PMN membrane sterol, with a subsequent alteration in membrane configuration, is the most likely cause of the inhibition of PMN function. The data collectively document biochemical and morphological differences between control and NF-treated PMNs as determined by stimulus-specific CL and O2- generation and membrane shape change. Such differences may account, in part, for its efficacy in inflammatory fungal skin diseases.

Allylamine↗

Monozygotic twins discordant for the acquired immunodeficiency syndrome.

Monozygotic twin girls discordant for acquired immunodeficiency syndrome were born to parents with antibodies to human T-cell lymphotropic virus type III. One twin had clinical evidence of the syndrome with tests positive for antibody, whereas the other at the age of 3 years was clinically, serologically, and virologically normal.

Acquired Immunodeficiency Syndrome↗

In vitro effect of isotretinoin on monocyte chemotaxis.

The effect of isotretinoin on the chemotaxis of human monocytes was studied in an in vitro system using a Nucleopore chamber. The chemoattractant used was zymosan-activated serum. Inhibition of monocyte chemotaxis was achieved with isotretinoin in concentrations of 1 X 10(-3) M and 5 X 10(-4) M. It is felt that the improvement seen in patients with inflammatory skin diseases such as cystic acne and acne conglobata who are treated with isotretinoin may in part be a result of this anti-inflammatory action.

Adult↗

Deficient concanavalin-A-induced suppressor-cell activity in patients with bronchial asthma, allergic rhinitis and atopic dermatitis.

Concanavalin-A (Con-A)-induced suppressor activity against the proliferative response of autologous lymphocytes to phytohaemagglutinin (PHA) was examined in the peripheral-blood lymphocytes from fourteen patients with bronchial asthma, ten patients with allergic rhinitis and eleven patients with atopic dermatitis and compared with eleven simultaneously studied healthy normals. Eight of fourteen patients (57%) with bronchial asthma, eight of ten patients (80%) with allergic rhinitis and five of eleven patients (45%) with atopic dermatitis demonstrated deficient Con-A-induced suppressor function. Abnormal suppressor-cell functions could play an important role in the pathogenesis of atopic states.

Asthma↗

Monoclonal antibody-defined B cell subsets in aging humans and Down's syndrome.

Peripheral blood from aging and young humans and patients with Down's syndrome, and from age- and sex-matched controls, was studied for the proportions of surface immunoglobulin (SIg+) bearing and monoclonal antibodies FMC1, and FMC7 defined B lymphocytes and B lymphocyte subsets using fluorescent-activated cell sorter. In aging humans, the proportion of SIg+ and FMC1+ (that detect all B lymphocytes) were comparable to simultaneously studied healthy young controls. However, FMC7+ (that detects a subset of B cells) B cells were significantly (p less than 0.05) increased when compared to young subjects. In aging subjects, the proportions of FMC7+ B cells were comparable to their FMC1+ B cells, whereas in young subjects FMC7+ B cells were a subset of FMC1+ B cells. In Down's syndrome, a phenomenon similar to aging humans was observed, that is the proportions of FMC7+ were increased when compared to age- and sex-matched controls and were comparable to their own FMC1+ B cells. This study demonstrates the abnormality of B lymphocytes in human aging and Down's syndrome. The significance of these findings is discussed.

Adult↗

Haemophilus influenzae septic thrombophlebitis following use of a "scalp-vein" needle.

Indolent Haemophilus influenzae type B septic thrombophlebitis developed in a 14-year-old boy two weeks after completing a course of intravenous antibiotics administered via a "scalp-vein" needle for an unrelated infection. Presumably, the primary disease (common variable immunodeficiency) contributed to the simultaneous occurrence of this uncommon complication of scalp-vein needle use, with an unusual pathogen.

Adolescent↗

Autologous mixed lymphocyte reaction in man. VII. Autologous mixed lymphocyte reaction in patients with bronchial asthma, allergic rhinitis and atopic dermatitis.

The proliferative response of T lymphocyte cultured with autologous non-T lymphocyte is known as the autologous mixed lymphocyte reaction (AMLR). In AMLR, both helper and suppressor functions are generated. In this investigation we have examined T cell proliferative responses in AMLR in 12 patients with bronchial asthma, 10 patients with allergic rhinitis, and 10 patients with atopic dermatitis and compared that with simultaneously studied healthy controls. Our data show that the T cell proliferation in AMLR in patients with bronchial asthma is significantly higher than that of healthy normals. However, AMLR response in patients with allergic rhinitis or atopic dermatitis is comparable to controls. Mechanisms for increased AMLR in patients with bronchial asthma are discussed.

Asthma↗

Monoclonal antibody defined T cell subsets and autologous mixed lymphocyte reaction in Down's syndrome.

Peripheral blood from 21 non-institutionalized children with Down's syndrome (DS) and 21 age and sex matched simultaneously studied healthy controls, was analysed for monoclonal antibody defined T cells and T cell subsets, using a fluorescence activated cell sorter, and the autologous (AMLR) and allogeneic mixed lymphocyte reaction (MLR). Total T cells (9.6+), OKT4+ (helper/inducer phenotype) and anti-Tac+ (activated T) cells were present in comparable proportions to that observed in the control group. In contrast, the proportion of OKT8+ (suppressor/cytotoxic phenotype) cells were significantly (P less than 0.05) decreased when compared to healthy controls. The proliferative response in the AMLR and MLR were comparable to control group. The significance of these results are discussed.

Antibodies, Monoclonal↗

Immunological studies in patients with isolated growth hormone deficiency.

The proportion of total T cells, OKT4+ (helper/inducer phenotype) T cells and activated T cells (Tac+) in four growth hormone deficient children were compared to simultaneously studied age and sex matched healthy controls. Proportions of OKT8+ T cells (suppressor/cytotoxic phenotype), and B lymphocytes (surface immunoglobulin positive) were increased when compared to healthy controls. Increased proportion of OKT8+ T cells resulted in abnormally low ratios of OKT4+/OKT8+ cells. Proliferative response to PHA and in the AMLR were comparable to the control group. In allogeneic MLR, T cells from three of four patients responded poorly and three of four patients non-T cells stimulated poorly in MLR. Con A activated suppressor cell activity was comparable to healthy control group. This study supports the role of growth hormone in certain immune response.

Antibodies, Monoclonal↗

Deficiency of suppressor T-cells in insulin-dependent diabetes mellitus: an analysis with monoclonal antibodies.

Peripheral blood from 25 patients with insulin-dependent diabetes mellitus was examined for any alteration in the proportions and or functions of immunoregulatory T-cell subsets, defined with monoclonal antibodies. Ten of 25 (40%) patients demonstrated deficiency of OKT8+ (suppressor/cytotoxic) T-cells. Eight of these 10 patients had abnormally high ratios of OKT4+/OKT8+ T-cells. Nine of 10 patients with abnormally low proportion of OKT8+ T-cells had deficient concanavalin A-induced suppressor cell activity against the proliferative response of autologous or allogeneic lymphocytes to phytohemagglutinin. No correlation was observed between the deficiency of suppressor T-cells and the control of diabetes. Therefore, it is likely that the deficiency of suppressor cells is related to insulin-dependent diabetes mellitus itself and not to the metabolic changes that are associated with diabetes mellitus. This study demonstrates both quantitative and qualitative deficiency of suppressor T-cells in at least some patients with insulin-dependent diabetes, that might play an important role in the pathogenesis and autoimmune manifestations of a proportion of patients with insulin-dependent diabetes mellitus.

Adolescent↗

Neutrophil chemotaxis by Propionibacterium acnes lipase and its inhibition.

The chemoattraction of Propionibacterium acnes lipase for neutrophils and the effect of lipase inhibitor and two antibiotic agents on the chemotaxis were evaluated. Of the various fractions tested, partially purified lipase (fraction 2c) was the most active cytotaxin produced by P. acnes. Serum mediators were not required for the generation of chemotaxis by lipase in vitro. Diisopropyl phosphofluoridate at low concentration (10(-4) mM) completely inhibited lipase activity as well as polymorphonuclear leukocyte chemotaxis generated by lipase. Tetracycline hydrochloride and erythromycin base at concentrations of 10(-1) mM and 1 mM, respectively, caused 100% inhibition of PMN migration toward lipase or zymosan-activated serum. The inhibiting activity of the antibiotics was directed against cells independently of any effect on lipase. Chemotaxis by P. acnes lipase suggests a wider role for this enzyme in the inflammatory process and the pathogenesis of acne vulgaris.

Chemotaxis, Leukocyte↗

Thymus-dependent membrane antigens in man: inhibition of cell-mediated lympholysis by monoclonal antibodies to TH2 antigen.

In prior studies a heteroantiserum to a surface membrane component termed T(H2) was used to define two subsets of human T cells (T(H2) (+) and T(H2) (-)), which were found to express distinct sets of activities in vitro. In the present studies we prepared monoclonal antibodies to surface determinants that are restricted to T cells belonging to each of these two subsets. Two antibodies, termed alphaLeu-2a and alphaLeu-2b, which seem to define the same surface antigen identified by the original T(H2) antiserum, reacted with 57-84% of thymocytes and 22-46% of the erythrocyte-rosette-forming cells (ERF-C) in peripheral blood. Two other monoclonal antibodies, termed alphaLeu-3a and alphaLeu-3b, reacted with the same subpopulation of thymocytes (78-89%) and peripheral blood ERF-C (47-78%) but, unlike alphaLeu-2a and alphaLeu-2b, did not exhibit cross-blocking; i.e., labeling cells with alphaLeu-3a did not inhibit the subsequent binding of alphaLeu-3b. T cells reactive with alphaLeu-2a were shown to be unreactive with alphaLeu-3a, indicating that two separate subpopulations of T cells, Leu-2 (formerly T(H2) (+)) and Leu-3 (T(H2) (-)) T cells, were thereby defined. These two T cell subsets make up the subpopulation of ERF-C (80-95%) previously defined by a monoclonal antibody to a T cell membrane antigen (Leu-1) that has a thymus-dependent distribution on normal lymphocytes but is expressed by some surface-immunoglobulin-positive (sIg(+)) leukemic lymphocytes. None of the Leu antibodies reported here reacted with sIg(+), Leu-1(+) leukemic cells, nor did they react with normal hematopoietic cells or lymphoid cells that had surface markers characteristic of B cells. Studies of the blocking effects of Leu antibodies on killing in cell-mediated lympholysis by effector T cells were carried out in the absence of complement. These experiments established the following points: (i) alphaLeu-2a abolished the killing by cytotoxic T cells of allogeneic phytohemagglutinin-stimulated blasts, (ii) inhibition of killing by alphaLeu-2b was markedly less than inhibition by alphaLeu-2a, and (iii) other antibodies, including alphaLeu-1, alphaLeu-3a, and alphaLeu-3b, had little or no effect on killing in cell-mediated lympholysis. The relevance of these findings to prior studies done in the mouse and in man are discussed.

Animals↗

Fibroblast nitroblue tetrazolium test and the in-utero diagnosis of chronic granulomatous disease.

A quantitative nitroblue tetrazolium (NBT) test was devised to measure dye reduction by fibroblasts. Statistically significant differences were found between NBT reduction by normal skin and amniotic fibroblasts and by skin fibroblasts of male patients with chronic granulomatous disease (CGD) and their carrier relatives. Cultured amniotic cells may therefore be useful in the prenatal diagnosis of X-linked CGD.

Amniocentesis↗

Chronic granulomatous disease and McLeod syndrome in a black child.

A 3-year-old black male child with X-linked chronic granulomatous disease and red cells of the rare McLeod phenotype is presented. The red cells showed acanthocytosis and did not react with anti-KL. Similarly the leukocytes were nonreactive with anti-Kx. The Xk and Xg linkage could not be investigated since all members of his family were Xg (a+).

Acanthocytes↗