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Biomedical subjects

D Wallach

Publications and source records attributed to D Wallach.

At least 217 records · Page 12Linked to original sources
PubMed1983

Quantification of the antiviral effect of interferon by immunoassay of vesicular stomatitis virus proteins.

A simple solid-phase immunoassay for quantification of vesicular stomatitis virus (VSV) is described. Infected cultures are lysed with deoxycholate. Samples of the lysates are transferred to PVC immunoassay plates and the amount of virus protein adsorbed to the plates is then quantified by sequential incubation with antiserum against VSV proteins and 125I-labelled Protein A. The decrease of VSV protein in interferon (IFN)-treated cultures is correlated with inhibition of formation of infectious virions; its quantification therefore allows accurate measurement of the antiviral effect. The applicability of the immunoassay for measuring the virus yield is not restricted to cells exhibiting a virus cytopathic effect. Moreover, since the decrease of virus protein is obtained at IFN concentrations lower than those that reduce cell killing by the virus, the assay provides a more sensitive measure for the IFN effect than that obtained by 'cytopathic effect inhibition' assays.

Cell Line↗
PubMed1983

In vitro proliferative response to M. leprae and PPD of isolated T cell subsets from leprosy patients.

In vitro proliferative response to Mycobacterium leprae and PPD to T cell subsets, isolated by selective depletion procedure from peripheral blood using OKT4 or OKT8 monoclonal antibodies plus complement, was investigated in leprosy patients. Whole peripheral blood mononuclear cells (PBMC) developed a strong proliferative response to both M. leprae and PPD in most tuberculoid patients. This proliferation was confined to T cells, and concerned predominantly OKT4+ cells. Both antigens, however, induced a smaller, but significant proliferation oF OKT8+ cells. In lepromatous patients, proliferative response of whole PBMC incubated with M. leprae was in most cases unsignificant, at variance with PPD-induced proliferation, which was not significantly lower than that of PBMC from tuberculoid patients. In a majority of M. leprae non-responders, neither OKT4+ nor OKT8+ enriched PBMC developed a proliferative response to M. leprae. Unexpectedly in four M. leprae unreactive patients, control treatment of PBMC with complement alone restored a strong proliferative response to M. leprae. Taken together, these results suggest that in vitro unresponsiveness to M. leprae results at least in some patients, from an active suppressor mechanism but that the effector phase of such suppression does not directly involve OKT8+ T cells.

Adolescent↗
PubMed1982

Preferential effect of gamma interferon on the synthesis of HLA antigens and their mRNAs in human cells.

Interferons produce a variety of biological effects on cells. They induce resistance to virus proliferation, inhibit cell growth, modify cell structure and differentiation, stimulate some immune functions and inhibit others. However, the different interferon (IFN) species may vary in their mechanism of action and, hence, in their relative efficiency for inducing each of the effect. IFN-gamma (type II) appears to show stronger immunoregulatory and growth inhibitory effects than antiviral effects, but this conclusion has been challenged in other reports. The aim of the present work is to compare the action of IFN-gamma and other (type I) interferons on the induction of (2'-5') oligo(A) synthetase which is probably part of the antiviral response and the induction of the histocompatibility HLA-A,-B,-C antigens. We have shown previously that the induction of both proteins is regulated by interferons at the mRNA level, but show here that IFN-gamma from stimulated human lymphocytes and from monkey cells transfected by cloned human IFN-gamma cDNA induced the HLA-A,-B,-C and beta 2-microglobulin mRNAs or proteins at concentrations over 100 times lower than those needed to induce the (2'-5')oligo(A) synthetase and the antiviral state. This difference was not found with IFN-alpha and -beta (type I).

2',5'-Oligoadenylate Synthetase↗
PubMed1982

Interferon-dependent induction of mRNA for the major histocompatibility antigens in human fibroblasts and lymphoblastoid cells.

In human cells treated with interferons, there is an increase in the amount of HLA-A,B,C and beta 2-microglobulin exposed on the cell surface. We have used a cloned HLA-A,B,C cDNA probe to demonstrate by molecular hybridization that this effect of interferon is preceded by a large increase in the amount of HLA mRNA in the cell. This effect was found in five different human cell lines, with purified leukocyte and fibroblast interferons. The increase in HLA mRNA is comparable in its kinetics and dose-response to the induction of (2'-5') oligo(A) synthetase mRNA by interferons. Therefore, interferons seem to activate at least two cellular genes which have different biochemical functions.

Cells, Cultured↗
PubMed1982

Comparison of (2'-5') oligo-adenylate synthetase and interferon blood-levels in mice early after viral infection.

The level of the IFN-induced enzyme (2'-5') oligo A synthetase in the peripheral blood mononuclear cells (PBMC) was determined in mice at different times following virus infection. There was a significant increase (4-7-fold) of the enzyme level within less than 12 h after i.p. injection of either VSV (10(7) pfu) or Sindbis virus (2.10(4) pfu). The elevated level was maintained for about a week and then the activity returned to normal. There was, however, a marked difference in the pattern of serum level of IFN during infection by the two viruses; while in the mice infected by VSV, serum IFN was very high on the first day and declined to an undetectable level by the fourth day, in the mice infected with Sindbis virus, serum IFN was barely detectable at the first day and then increased towards the fourth day of infection. Antiviral antibodies could be detected in the serum only about a week after infection. We conclude that viral infection can result in a rapid elevation of (2'-5') oligo A synthetase in the PBMC, even when serum IFN remains low. Thus, quantitation of the enzyme level can be a useful diagnostic aid in viral infection particularly in the early stages and in cases in which antiviral antibodies and IFN can not be detected.

2',5'-Oligoadenylate Synthetase↗
PubMed1982

Regulation of susceptibility to natural killer cells' cytotoxicity and regulation of HLA synthesis: differing efficacies of alpha, beta, and gamma interferons.

Interferon (IFN) is an effective activator of the natural killer (NK) cells but can also induce, in a variety of target cells, resistance to the NK induced cytolysis. We have compared the ability of the various types of human IFN to carry out this function, by quantitating the cytolysis induced by NK cells in cultured fibroblasts pretreated with each IFN and comparing this effect of the IFNs to their effectivity in suppressing viral replication. Relative to their antiviral potency, preparations of IFN-gamma were significantly more effective than the alpha or beta interferons in inducing what we call the "anti-NK" effect. Significant inhibition of the natural killing was observed with IFN-gamma even at concentrations at which no antiviral effect was induced. Preparations of IFN-gamma were also more effective than the other interferons in suppressing cell growth. While the induction of the enzyme oligo-isoadenylate synthetase correlated to the antiviral effectivity of the interferons, the quantitation of the HLA proteins in the cells had shown that their induction by the interferons correlates to the induction of the anti-NK effect, being stimulated much more effectively by IFN-gamma than by IFN-alpha or IFN-beta. The anti-NK, HLA and antiviral-inducing activities co-purified in fractionation of IFN-gamma preparations. These findings suggest the existence of several independent mechanisms for the regulation of cell functions by interferons. The gamma IFN is particularly effective in regulating functions involved in the interaction of cells with the immune system while the gamma virus-induced IFN-alpha and -beta are more effective as inducers of resistance to viral growth.

Cells, Cultured↗
PubMed1982

Variation of (2'-5') oligo A synthetase level in lymphocytes and granulocytes of patients with viral infections and leukemia.

Using a simplified technique for the determination of oligoisoadenylate synthetase activity, we have compared the cellular level of this interferon (IFN)-induced enzyme in multiple samples of peripheral blood leukocytes. In mononuclear cells (PBMC) of healthy donors the enzyme level was remarkably constant, but in the cells of about 85% of patients with viral infections enzyme activity was significantly elevated. In contrast, the incidence of elevated activity in bacterial infections was low. Synthetase activity could be also detected in granulocytes, although normally its level in these cells was considerably lower than in PBMC. A sharp increase in the enzyme level in granulocytes was found in cells exposed in vitro to IFN, as well as in cells from patients undergoing IFN therapy. Increased synthetase activity was also detected in the granulocytes of patients with viral infections. We have also determined the level of the enzyme in patients with various types of leukemias. In a large proportion of the patients with acute lymphoblastic leukemia (ALL) we found severely decreased enzyme levels (10-20% of control value). The decreased activity could usually be correlated to predominance of blast cells in the peripheral blood.

2',5'-Oligoadenylate Synthetase↗
PubMed1982

Inhibition by glucocorticosteroid hormones of interferon and prostaglandin E induction by poly(rI). Poly(rC).

We have examined the relationship between induction of interferon (IFN) and prostaglandin E (PGE) production by poly(rI).poly(rC) in cultured human foreskin fibroblasts (FS11). Hydrocortisone and dexamethasone (2 . 5 x 10(-7) M), which are known inhibitors of PGE synthesis, significantly decreased the induction of both IFN and PGE in IFN-pretreated (primed) cells. Desoxycorticosterone, progesterone and estradiol were devoid of this activity. Hydrocortisone also blocked the induction of IFN by double-stranded RNA (dsRNA), cycloheximide and actinomycin D in FS11 cells. Arachidonic acid overcame the inhibitory effect of hydrocortisone on PGE production, but failed to restore IFN production in the presence of the steroid. Moreover, the prostaglandin synthetase inhibitors, indomethacin, aspirin and flufenamic acid, did not change IFN production by dsRNA in primed FS11 cells, although prostaglandin synthesis was abolished. Although the induction of IFN and PGE by poly(rI).poly(rC) might be consequences of the same initial event in the cell, the accumulation of PGE does not seem to have a regulatory effect on the synthesis of IFN in this system.

Cells, Cultured↗
PubMed1982

Subcorneal pustular dermatosis and monoclonal IgA.

A patient with subcorneal pustular dermatosis was found to have a circulating monoclonal IgA kappa immunoglobulin. Direct immunofluorescence studies revealed IgA kappa deposits in the subcorneal zone of the epidermis. Circulating IgA kappa reacting with the subcorneal zone of normal human epidermis was demonstrated by indirect immunofluoresence. It is speculated that IgA deposition might be implicated in the pathogenesis of subcorneal pustular dermatosis.

Aged↗
PubMed1982

Cimetidine versus placebo in the treatment of psoriasis.

A 2-month, double-blind, placebo-controlled clinical trial was undertaken to evaluate the effectiveness of cimetidine in the treatment of chronic, plaque-type psoriasis. 24 patients completed the trial (11 treated with cimetidine, 13 with placebo). 3 patients in the cimetidine group and 10 in the placebo group improved. This difference is significant (p less than 0.01). Cimetidine had to be discontinued in 2 patients because of side effects. In this study, cimetidine proved of no benefit in the treatment of psoriasis. Furthermore, our results suggest the possibility of an adverse effect of cimetidine in psoriasis.

Adult↗