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Biomedical subjects

D Wallach

Publications and source records attributed to D Wallach.

At least 199 records · Page 11Linked to original sources

Translation of mRNA for human lymphotoxin in microinjected Xenopus oocytes.

Synthesis and secretion of biologically active human lymphotoxin (LT) can be detected in Xenopus laevis oocytes following their inoculation with poly(A+) RNA from human stimulated peripheral blood lymphocytes, but not in oocytes inoculated with RNA from unstimulated lymphocytes or from fibroblastoid cells. In size-fractionating mRNA of stimulated lymphocytes most LT activity is found to be coded for by RNA with an approximate sedimentation value of 19 S.

Animals↗

An immunoenzyme quantitative assay for the antiviral effect of interferons.

A technique is described for measurement of the antiviral activity of interferon by an immunoenzymatic assay for viral proteins. Cells treated by tested samples of interferon (IFN) are infected with vesicular stomatitis virus (VSV) and following the development of viral cytopathy are lysed by the addition of deoxycholate and then transferred into ELISA microplates. The viral proteins bind effectively to the microplates proportionally to their level in the culture and may be measured by incubating the plates sequentially with (1) rabbit antiserum against VSV, (2) a conjugate of alkaline phosphatase either to protein A or to an antibody against rabbit IgG and (3) p-nitrophenylphosphate. This procedure may be further simplified by using antibodies against VSV to which alkaline phosphatase has been directly conjugated. We found this immunoenzyme assay to be superior to the 'cytopathic effect inhibition' assay in precision and sensitivity and in being independent of the effectiveness of viral cytopathy.

Adsorption↗

Intramuscular human interferon-beta injections in treatment of condylomata acuminata.

A two-part study was done to assess the value of human fibroblast interferon (IFN-beta) in the treatment of condylomata acuminata. The first part was an open study of different IFN-beta preparations, which showed that intramuscular injection was the most suitable mode of administration of IFN-beta. In the double-blind placebo section 22 patients were given injections of 2 X 10(6) units IFN-beta or placebo for 10 consecutive days and followed up for 3 months. In 9 of the 11 in the IFN-beta group and 2 in the placebo group lesions disappeared from about 5 weeks after completion of the course of injections. After 3 months 8 of the non-responders were given a course of IFN-beta and all responded to treatment. None of those who had responded has had a recurrence, the disease-free period now being 12 months. Changes in (2'-5')oligo A synthetase levels in white blood cells confirm that intramuscular injections of IFN-beta produce a systemic response.

2',5'-Oligoadenylate Synthetase↗

Interferon-induced cytotoxicity and (2'-5') oligo(A) synthetase activity in T cells. Differences in responsiveness among T cells from various individuals and among lymphoblastoid T-cell lines.

Peripheral blood T lymphocytes became cytotoxic toward Daudi lymphoblastoid cells when incubated in vitro with interferon (IFN). The degree and rate of response to IFN varied markedly from one blood donor to another. "Low responders," who reproducibly showed a slower response to IFN, as well as "high responders" could be identified. The rate of increase in (2'-5') oligo(A) synthetase activity in IFN-treated cells also varied and appeared to correlate to the rate of increase in cytotoxicity. Three lymphoblastoid T-cell lines (Molt 4, Peer, HPB-ALL) also became cytotoxic towards Daudi cells when incubated with IFN and in these cells too the rate of induction of cytotoxicity appeared to correlate to the rate of increase in (2'-5') oligo(A) synthetase activity. Differences in responsiveness of T cells to IFN-mediated cytotoxicity might, therefore, reflect differences in responsiveness to IFN in general. Thus, quantitation of these differences might yield useful information for assessing the dosage and frequency of IFN administration to patients undergoing therapy.

2',5'-Oligoadenylate Synthetase↗

The cellular content of dermal leprous granulomas: an immuno-histological approach.

An indirect immunofluorescence technique with monoclonal antibodies has been used to identify T cells, T helper cells, T suppressor cells, and granulocytes in the dermal granulomas of 22 patients with leprosy. In tuberculoid leprosy, T helper cells predominated and T suppressor cells were located at the periphery of well-circumscribed granulomas. In lepromatous leprosy, the two subsets of T cells were numerous in treated patients. In ENL lesions, T cells were more numerous and T helper cells predominated. Enumerations of the T cell subsets in the dermis and in the blood showed similar changes, but these changes were quantitatively more marked in the dermal granulomas.

Adolescent↗

[Subcorneal pustulosis and monoclonal gammapathies].

Subcorneal pustular dermatosis (Sneddon-Wilkinson) is a rare dermatosis. In some cases, it is associated with a monoclonal gammopathy, most often Ig A. This association is considered as a salient feature of SPD, and is not present in other pustuloses, like pustular psoriasis, which may be related to SPD. The physiopathology of the neutrophilic dermatoses and the role of Ig A are briefly discussed.

Aged↗

(2'-5') Oligo A synthetase in human polymorphonuclear cells increased activity in interferon treatment and in viral infections.

The interferon (IFN)-induced enzyme 2-5A synthetase was found in human peripheral blood polymorphonuclear cells (PMNL). The average enzyme activity in a group of 15 patients with various viral infections was significantly higher (25-fold) than in healthy individuals. Eight patients with multiple sclerosis and six patients with bacterial infections were found to have normal 2-5A synthetase levels in the PMNL. Relationship of PMNL 2-5A synthetase levels to IFN was confirmed by finding enzyme increases in PMNL incubated in vitro with IFN, as well as in patients undergoing IFN therapy. These findings suggest that in PMNL, as in other cells, the level of 2-5A synthetase can be regulated by IFN and can be increased as a result of IFN information in diseases.

2',5'-Oligoadenylate Synthetase↗

[Striated lichenoid keratosis. 2 cases with oral manifestations].

We present two cases of keratosis lichenoides striata. Both patients have the typical features of the disease: linear verrucous formations on the limbs, and a seborrheic--like dermatitis. The oral mucosa was involved, showing erythematous patches and papules. A treatment by etretinate did not bring a significant improvement.

Adult↗

[Epidermal nevus syndrome. A case with oral involvement].

We report the case of a girl with a large epidermal nevus involving the right superior part of the body, i.e. scalp, face, neck, chest, and oral mucosa. Stress is laid on the clinical features of the mucosal involvement of the épidermal nevus syndrome.

Adult↗

Preparations of lymphotoxin induce resistance to their own cytotoxic effect.

Preparations of human lymphotoxins (LT) were effectively cytotoxic to HeLa cells when applied in the presence of cycloheximide (CHI). In the absence of CHI, however, they failed to cause any cell death. Moreover, LT applied in the absence of CHI induced resistance that was reflected in decreased vulnerability to subsequent incubation with LT in the presence of CHI. This induction of resistance to LT, in treating cells with preparations of LT, was quite rapid, reaching its maximal extent within 2 hr of LT application. It could also be observed in cells of other cultured human lines besides HeLa (SV80 and WISH), and the range of LT concentrations at which it was observed was similar to that at which death of cells was induced by LT in the presence of CHI. In fractionating LT preparations on DEAE cellulose, the resistance inducing activity appeared to co-purify with the cytotoxic activity, suggesting that both activities reside in the same molecule. We suggest that LT, or some lymphokines that are formed by lymphocytes concomitantly with the formation of LT, can induce cellular mechanisms that interfere with the cytotoxic activity of LT and that CHI makes the cell sensitive to the cytotoxicity of LT by reducing the activity of these protective mechanisms. This kind of negative feedback regulation in the function of LT might contribute to selectivity in their action.

Chromatography, DEAE-Cellulose↗

Involvement of interferon in virus-induced lymphopenia.

Intraperitoneal injection of vesicular stomatitis virus (VSV) into mice causes marked and rapid changes in leukocyte distribution. The virus induces an increase in peripheral blood (PB) granulocytes and an extensive decrease in the lymphocyte count which reaches a nadir of less than 10% of preinfection values, 12 hr after virus inoculation. In the lymph nodes and spleen extensive lymphocyte translocation and granulocyte infiltration are observed. Most changes abate 48 hr following virus inoculation. Injection of poly(rI):(rC) causes similar changes to those observed with VSV. The lymphocyte changes observed after injection of VSV or poly(rI):(rC) coincide with high levels of interferon (IFN) in the serum. We have examined the effects of anti-IFN antibody on those changes and investigated whether they can be mimicked by injecting IFN. Our findings suggest that the IFN induced by VSV or poly(rI):(rC), rather than those agents themselves, causes the observed lymphopenia as well as some of the changes observed in the spleen. On the other hand, the effects of VSV on granulocyte localization do not appear to be mediated by IFN.

Adrenalectomy↗

Interferon-induced resistance to the killing by NK cells: a preferential effect of IFN-gamma.

HeLa cells show a decrease of susceptibility to the killing by natural killer (NK) cells when treated with IFN-alpha, beta, or gamma. The concentrations at which preparations of IFN-alpha or beta induce the resistance to killing are those which also induce resistance of HeLa cells to infection by vesicular stomatitis virus (VSV). Stimulation of the killing activity of NK cells is also induced at that same range of concentrations of IFN-alpha and beta. In contrast with preparations of IFN-gamma, induction of the resistance to killing occurs at IFN concentrations which have only marginal stimulatory effect on the activity of NK cells and have no antiviral effect against VSV. IFN-gamma, produced with cloned IFN-gamma cDNA, is as effective as lymphocyte-produced IFN in inducing the resistance to natural killing. The potent effect of IFN-gamma on the target cells is, therefore, not due to the function of lymphokines which might contaminate lymphocyte-produced preparations of IFN-gamma, but a genuine property of the IFN itself.

Cytotoxicity, Immunologic↗

The HLA proteins and a related protein of 28 kDa are preferentially induced by interferon-gamma in human WISH cells.

The HLA-A,B,C proteins are preferentially induced by interferon (IFN)-gamma. An increase in their synthesis and of their expression on the cell surface can be observed at concentrations of IFN-gamma which are lower than those inducing an antiviral effect. On the other hand, with IFN-alpha and beta, induction of these proteins can be observed only in the antiviral range of IFN concentrations. In human WISH cells, IFN also induces a protein with a molecular mass of 28 kDa (28K). The efficiency of IFN-beta and gamma in inducing this protein is correlated to the efficiency with which they induce the HLA-A,B,C proteins. The 28K protein can be immunoprecipitated with antibodies against beta 2-microglobulin, just as the HLA proteins; yet it can be clearly distinguished from the HLA proteins in several respects: (a) it is not a cell surface protein but rather an intracellular one, with a relatively short half-life, (b) partial peptide mapping suggests that it contains sequences distinct from those of which the HLA alpha chains or beta 2-microglobulin are comprised and (c) the extent of its induction by IFN is much larger than that observed for the HLA proteins.

Antigen-Antibody Reactions↗

Differential regulation of HLA-DR mRNAs and cell surface antigens by interferon.

Human interferons-alpha, -beta and -gamma enhance HLA-DR mRNAs in all the human lymphoblastoid and melanoma cell lines studied. The increase concerns both alpha and beta chain mRNAs. Moreover, we show that immune interferon-gamma preferentially enhances class II MHC mRNA. This effect of IFN-gamma on the synthesis of alpha and beta HLA-DR chains has been also analysed by immunoprecipitation. It is abolished by a monoclonal antibody directed against human IFN-gamma. The effect of interferon on the cell surface level of HLA-DR molecules does not always correspond to the enhancement of HLA-DR mRNA. Our experiments suggest that this discrepancy between the enhancement of HLA-DR mRNA and cell surface antigen might be due to a constitutively high level of the corresponding antigens on several of the human cells studied.

B-Lymphocytes↗

Enhanced release of lymphotoxins by interferon-treated cells.

Pretreatment of human peripheral blood lymphocytes with interferon significantly enhances the release of lymphotoxins (LTs) observed at subsequent incubation of the cells, for 3 hr, with phytohemagglutinin (PHA). Fractionation of the LTs by gel filtration shows that interferon (IFN) strongly increases the release of certain LTs produced by these cells, while it has little effect on the release of others. The release of LTs from the IFN-treated cells is dependent on stimulation by PHA, requires Ca2+ ions, and can be blocked by prostaglandin E1, but it is independent of protein synthesis.

Cytotoxicity, Immunologic↗

Demonstration of T lymphocytes in leprous granuloma using the acid alpha naphtyl acetate esterase activity. An attempt at quantitative analysis.

In nine leprosy patients (1 TT, 1 BT, 4 BL and 3 LLp), esterase positive lymphocytes (T Lymphocytes) were studied in frozen sections of skin biopsies by alpha naphtyl acetate esterase pH 5.8 method (ANAE) Four patients had never been treated previously and five patients exhibited clinical and bacteriological evidence of relapse for inadequate therapy at first biopsy. There was an increase in ANAE (+) lymphocyte density in granulomas when second biopsies were done after efficient treatment, evaluated by bacillary index for the eight bacilliferous patients, and clinical improvement. The significance of T cells in granulomas is discussed.

Adult↗