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Biomedical subjects

D Wallach

Publications and source records attributed to D Wallach.

At least 181 records · Page 10Linked to original sources

Captopril-induced lichen planus pemphigoides with pemphigus-like features. A case report.

We report a case of a bullous lichenoid eruption due to the intake of captopril. Clinical, histological, direct immunofluorescence and ultrastructural features were consistent with the diagnosis of lichen planus pemphigoides. In addition, the in vivo immunological study also revealed an intercellular fluorescence, similar to that seen in pemphigus. Complex drug-induced cutaneous reactions have been previously reported with other drugs, especially with D-penicillamine, which bears chemical similarities with captopril. However, such a drug-induced mixed pattern of lichen planus pemphigoides with pemphigus-like features has never been reported.

Autoantibodies↗

Antibodies to phenolic glycolipid-1 and to whole Mycobacterium leprae in leprosy patients: evolution during therapy.

Sera from 92 patients were tested by the ELISA method for the presence of IgM antibodies to phenolic glycolipid-1 (PGL-1) of Mycobacterium leprae, and of both IgM and IgG antibodies to the whole M. leprae bacillus. All untreated lepromatous patients exhibited high antibody levels in all three assays. A sharp decline of IgM antibodies to PGL-1 and whole M. leprae was observed during the first two years of therapy, while IgG antibodies to whole M. leprae showed a progressive decrease only over a number of years. Low titers of IgM antibodies to PGL-1 and IgG antibodies to whole M. leprae could be detected in about 50% and 75% of patients, respectively, after more than ten years of treatment, with only 15% showing persisting IgM antibodies to the whole bacillus. Antibody levels as measured by the three assays used were correlated with the bacterial index in patients treated for less than four years. In patients treated longer than four years, only IgM antibodies, whether directed to PGL-1 or to whole M. leprae, remained correlated to the bacillary load. Tuberculoid patients exhibited a different antibody pattern, showing a lower frequency (and lower levels) of antibodies of PGL-1 and of IgG antibodies to whole M. leprae than lepromatous patients, and no detectable IgM antibodies to the whole bacillus. IgG antibodies to whole M. leprae were more frequently noted than antibodies to PGL-1, the latter declining more rapidly during therapy.

Antibodies, Bacterial↗

Plasma exchange in severe erythema nodosum leprosum.

Four patients with severe erythema nodosum leprosum were treated by plasma exchange and/or fresh frozen plasma infusions after failure of classical therapy. After the procedures, the patients improved rapidly; with a follow-up between 4 and 7 years after the last plasma exchange, no clinical relapse was noted. The replacement fluids were variable; the most beneficial procedure seemed to be plasma exchange replaced with fresh frozen plasma. Elimination of circulating immune complexes, replacement of a lacking plasma factor are possible mechanisms of action. Plasma exchange may also work like a regulator of immune mechanisms, since it has been shown that there is a depression of suppressor cells in erythema nodosum leprosum.

Adult↗

Increase of vulnerability to lymphotoxin in cells infected by vesicular stomatitis virus and its further augmentation by interferon.

The cytotoxic effect of lymphotoxin (LT) and its modulation by interferon (IFN) was quantitatively assessed in uninfected and vesicular stomatitis virus (VSV)-infected cultured cells. Preparations of human LT, which were depleted of IFN, had a significant cytotoxic effect on VSV-infected HeLa, SV-80, WISH, and Vero cells. IFN, most notably IFN-gamma, further potentiated destruction of the infected cells by these LT preparations, when applied on the cells at sub-antiviral IFN concentrations. In contrast, no cytotoxic effect could be observed in any of the examined cells, when applying LT, IFN, or their combination, in the absence of viral infection. Infected cells in which VSV replication was suppressed by treatment with antiviral concentrations of IFN also resisted destruction by LT. These findings indicate that LT cytotoxicity can be selectively directed against virus-infected cells and that IFN can augment this cell-killing mechanism when failing to exert an antiviral effect.

Animals↗

Specificity study of PPD-reactive human T cell line and clones.

Peripheral blood mononuclear cells from a PPD-sensitive human subject, in vitro stimulated by PPD, could be maintained for several weeks in interleukin 2-containing medium, with regular reactivation with PPD and irradiated autologous mononuclear cells used as antigen-presenting cells. The proliferative response of this T cell PPD-reactive bulk culture could be stimulated to proliferate by PPD itself as well as by BCG and other mycobacteria. This T cell line comprised a majority of T cells expressing the OKT4+, OKT8- phenotype, and a minor proportion of T cells (8%) showing the OKT4-, OKT8+ phenotype. Two PPD-reactive clones, both OKT4+, were obtained from this line by the limiting dilution technique. Clone C9 was found to be highly specific of PPD and BCG, whereas clone A9 could be activated by four other species of mycobacteria. These data demonstrate the existence of species-specific and cross-reactive epitopes within PPD and prompt for the use of PPD-reactive clones as a tool for identification and purification of the molecules bearing these epitopes.

Cell Line↗

Identification of viral infections in pregnancy by assay of (2'-5')-oligo-isoadenylate synthetase.

Interferons are produced in response to viral infections. Among the biochemical changes they cause in cells is the induction of the enzyme (2'-5')-oligo-isoadenylate synthetase. The activity of this enzyme can be measured and this can indicate exposure and response of cells to interferon. The efficacy of such an assay of peripheral blood of pregnant women may aid in establishing screening guidelines for potentially teratogenic viral infections. The blood of 44 primigravidas with complaints of fever, myalgia, cough, vaginal discharge and/or costovertebral angle tenderness was assayed for activity of the enzyme (2'-5')-oligo-isoadenylate synthetase and compared to assays of the enzyme activity in a group of 37 healthy primigravidas which served as a control group. It was found that the group with viral infections had an increase in enzyme activity from twice to 15 times the normal value, with characteristic rises of enzyme activity in several viruses known or suspected to cause human defects. Several general guidelines are proposed to assist the obstetrician in determining a viral etiology of acute illness in pregnancy, It is suggested that the assay of enzyme activity of (2'-5')-oligo-isoadenylate synthetase may provide a simple tool for rapid diagnosis of viral infections in pregnancy.

Adult↗

Involvement of cytotoxins in the immune response to viral infection.

A human cytotoxin (CTX) with an Mr of 17,500 was purified to homogeneity from cytokine preparations by the use of a monoclonal antibody against that protein. Sendai virus and, to a lesser extent, the lectin phytohemagglutinin were found to induce effective production of that CTX in cultures of human peripheral-blood mononuclear cells, the first - by stimulating monocytes to produce the proteins, and the latter - by stimulating T cells. With both kinds of inducers, CTX production correlated to a marked increase in the cellular levels of mRNA for CTX, as quantitated by translation of that mRNA, to biologically active CTX, in microinjected Xenopus oocytes. Crude CTX preparations, as well as purified CTX, were found to be selectively cytotoxic to metabolically depressed and to virus infected target cells; they effectively killed cells which were treated with inhibitors of macromolecule synthesis, such as cycloheximide, or infected by viruses, such as VSV, but failed to exert a cytotoxic effect in the absence of such sensitizing treatments. IFN, most notably IFN-gamma, further potentiated destruction of virus-infected cells by the purified CTX, when applied on these cells at subantiviral concentrations, while uninfected cells remained resistant to CTX following treatment with IFN. Formation of the 17.5K CTX in response to viral infection and the selective cytotoxic effect of that protein on cells infected by viruses, indicate a role of CTX in the defense against viral infections.

Animals↗

Use of monoclonal antibodies to a human cytotoxin for its isolation and for examining the self-induction of resistance to this protein.

Crude preparations of cytotoxins (CTXs) produced by human peripheral blood mononuclear cells exert a marked cytotoxic effect when applied to cells in the presence of cycloheximide but in its absence can induce resistance to cytotoxicity. To examine the relationship between these cytotoxic and protective activities, we attempted to fully dissociate the CTX from the other proteins secreted by mononuclear cells. Mice injected with preparations of the cytokines secreted by peripheral blood mononuclear cells developed significant titers of serum antibodies to CTX(s). Splenocytes of such immunized mice were fused with NSO myeloma cells; a few among the resulting hybridoma cells secreted CTX-binding antibodies. Immunoadsorbents constructed with a monoclonal antibody produced by one of these hybridomas were used to purify to homogeneity a CTX (Mr approximately 17,500) from crude preparations of cytokines, by a single adsorption and elution cycle. Purified CTX was cytotoxic in the presence of cycloheximide but in its absence induced resistance to cytotoxicity; this resistance was manifested by decreased vulnerability to CTX in a subsequent incubation in the presence of cycloheximide. We conclude that CTX itself can induce certain changes in cells, which are reflected in resistance to its own cytotoxic effect.

Animals↗

Rapid improvement in a terminal case of hairy cell leukemia treated with a new human recombinant interferon, IFN-alpha-C.

A new type of human interferon (IFN), IFN-alpha-C, produced in Escherichia coli and purified on monoclonal antibodies, was given at a dose of 3 X 10(6) u (3 micrograms)/day to a terminally ill unsplenectomized patient with hairy cell leukemia, who had had severe recurrent infections and pancytopenia. There was marked reduction in the size of the spleen after 2 weeks, and platelet counts returned to normal after 1 month of treatment. The IFN treatment also raised the granulocyte counts and hemoglobin levels, improved the normal repopulation of the bone marrow, and restored resistance to infections. IFN-alpha-C was well tolerated, without serious side effects, and treatment has been continued for 10 months.

Cytotoxicity Tests, Immunologic↗