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Biomedical subjects

M Pecht

Publications and source records attributed to M Pecht.

34 records · Page 2Linked to original sources
PubMed1989

Immunopotentiation and pregnancy loss.

To test the hypothesis that immunopotentiation of the maternal immune system is beneficial for the developing embryo, we examined (1) the effect of specific preimmunization with paternal leucocytes in women and BALB/c splenocytes in CBA/J x DBA/2J mice (which show increased % fetal resorption) and (2) the influence of non-specific potentiators such as complete Freund's adjuvant and thymus humoral factor on the abortion rate in CBA/J mothers. Subsequent pregnancy was successful in 76% of habitually aborting women after immunization with paternal leucocytes. Immunization of CBA/J mice with complete Freund's adjuvant (2 foot-pad injections) decreased the resorption rate (11.3% vs 34.9% without treatment). The effect was followed by a slight decrease of the L3H4-positive lymphocyte subpopulation in the spleen but not in the draining lymph nodes, as measured by flow cytometry analysis. The amount of Lyt-2 positive lymphocytes was not changed as a result of treatment. Thymus humoral factor did not influence the abortion rate in CBA/J females mated with DBA/2J male mice. Our results show that non-specific stimulation of the maternal immune system by complete Freund's adjuvant can improve reproductive success in allogeneic mice with increased pregnancy loss. The exact mechanism of this improvement is still unclear but it seems that systemic cellular mechanisms are not responsible for the effect.

Abortion, Habitual↗
PubMed1988

Thymic humoral factor gamma 2: purification and amino acid sequence of an immunoregulatory peptide from calf thymus.

Thymic humoral factor gamma 2 (THF-gamma 2), an octapeptide essential for immune regulation, was purified from calf thymus. The purification of THF-gamma 2, monitored in vitro and in vivo in mouse splenocyte proliferation assays, was achieved by gel filtration of low molecular weight thymus extracts followed by ion-exchange chromatography and sequential reversed-phase high-performance liquid chromatography. The process yielded 5 micrograms of THF-gamma 2/1000 kg of thymus tissue. The concentration of THF-gamma 2 required for augmentation of lymphocyte proliferation and interleukin 2 production was 5 ng/mL in vitro and 10 ng/kg per mouse in vivo. THF-gamma 2 has the amino acid sequence Leu-Glu-Asp-Gly-Pro-Lys-Phe-Leu. The proposed structure has been confirmed because a peptide was synthesized on the basis of this sequence that showed activity identical with that of the biological molecule. It shows no homology to the amino acid sequence of other thymic hormones nor is it part of any peptide or protein of known sequence. THF-gamma 2 retains essentially all of the biological activity of the thymus extract from which it is derived.

Amino Acid Sequence↗
PubMed1987

Immunologic dysregulation in a patient with familial hemophagocytic lymphohistiocytosis.

A 6-year-old Jewish Iranian girl with familial hemophagocytic lymphohistiocytosis (FHLH) is described. The course of the disease fluctuated with partial initial response to antibiotics, steroids, and supportive treatment. Subsequent cytotoxic treatment, including VP-16, Velban (vinblastine sulfate), and methotrexate (MTX) controlled the disease for a few months but the child died with a clinical picture of meningocephalitis 1.5 years later. Benign-looking lymphohistiocytic infiltrates with varying degrees of hemophagocytosis were present in the bone marrow, pleural effusion, cerebrospinal fluid (CSF), liver, and brain. Clinical and laboratory evidence of immunologic dysregulation during the disease could be demonstrated. Frequent and intense viral and bacterial infectious diseases were encountered. The laboratory examination most consistently found was the absence of natural killer (NK) cell activity against K562 target cells. The impaired activity of NK cells persisted during all stages of the disease including remission, although NK cell numbers, determined morphologically and immunophenotypically (by Leu-11, Leu-7), were normal. Natural killer activity could not be restored by interferon. Moreover, the interferon system appeared to be intact. Impaired monokin interleukin 1 (IL-I) production by peripheral blood monocytes was found and could not be restored by indomethacin. Lymphopenia, a mild decrease in T4 numbers, and subsequently, decreased proliferative response to mitogens was noted. Elevated immunoglobulin levels were found during exacerbations and viral episodes, at times accompanied by the presence of auto-antibodies. The exaggerated fatal lymphohistiocytic response typical for FHLH could be attributed to a underlying genetic pathologic dysregulation of the various immunological response pathways.

Child↗
PubMed1987

Immune impairments and antibodies to HTLVIII/LAV in asymptomatic male homosexuals in Israel: relevance to the risk of acquired immune deficiency syndrome (AIDS).

We have studied 288 Israeli asymptomatic male homosexuals (MHS) to determine the prevalence of antibodies to HTLVI and HTLVIII and their correlation with impairments of the immune system and serum interferon (IFN). Seropositivity for HTLVI, HTLVIII, or both was found in 1.4, 8.3, and 0%, respectively. Significant decreases in the total peripheral T cells, TH cells, and TH/TS ratio as well as elevated alpha IFN serum levels were found in the MHS group in comparison with normal controls. Although no difference in the prevalence of either immune derangements or elevated serum IFN was observed between HTLVIII/LAV-seropositive and HTLVIII/LAV-seronegative MHS, the decreases in total T cells, TH cells, and TH/TS ratios were significantly greater in the seropositive MHS. These results indicate that (a) immune impairments and IFN system activation occur commonly in homosexuals, precede their exposure to HTLVIII/LAV, and probably reflect this group's increased risk for AIDS and (b) HTLVIII/LAV infection of MHS aggravates further their preexisting immune impairments.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Immunologic alterations in MRL/lpr mice after chronic dimethyl sulfoxide administration.

Dimethyl sulfoxide (DMSO) in 1 and 2% concentration was added to the drinking water of 30-100 day MRL/lpr mice. In comparison to control mice, the DMSO treated mice had a 78% increase in their response to exogenous IL-2 and a 64% increase in production of IL-2. Con A stimulated cells had a net help effect in the untreated mice, which was suppressed from 82-26% after DMSO treatment. There was no marked change in Thy 1.2, Lyt 1 and Lyt 2 percentages after treatment. The anti-DNA decreased from 29.0 +/- 17.0% to 13.2 +/- 7.8% after DMSO treatment. We conclude that chronic DMSO administration to MRL/lpr mice can induce immunologic alterations with possible clinical implications.

Animals↗
PubMed1987

Immunoreconstitution of T-cell impairments in asymptomatic male homosexuals by thymic humoral factor (THF).

The feasibility of using Thymic Humoral Factor (THF) for immunomodulation in asymptomatic male homosexuals was evaluated in a study on fifteen subjects with T-cell impairments, selected on the basis of a 2SD reduction in T helper/inducer (T4+) cells and one additional lymphocytic defect. Following two biweekly courses of treatment, mean relative increments of T4+ (P less than 0.002), T3+ (P less than 0.02) and total lymphocyte (P less than 0.05) populations of the group receiving THF (n = 7) were significantly increased when compared to the placebo group (n = 8). In addition, a transient increase in T4+ lymphocytes was observed after the first course in the two individuals of the THF-treated group who were seropositive for HTLV-III/LAV but not in those who were seronegative. No difference was found between the groups in fluctuations of serum interferon (IFN) or proliferation of peripheral mononuclear cells to mitogens. The results of this limited trial demonstrate that THF is capable of correcting T-cell impairments that may predispose asymptomatic homosexuals to infection by HTLV-III, without affecting IFN production. These findings suggest that future strategies for AIDS prevention in high-risk groups should include institution of large controlled trials in immunodeficient, asymptomatic, HTLV-III/LAV-seronegative male homosexuals to study the potential of selective immunoreconstitution as a preventive measure against HTLV-III/LAV infection.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Restoration of immunological responses by THF, a thymic hormone, in mice infected with murine cytomegalovirus (MCMV).

Cytomegalovirus causes T cell immune impairment in infected mice, reflected by a decreased response to the T cell mitogens PHA and Con A, and reduction of Con A-induced IL-2 secretion. Concomitantly, a marked increase in the spleen weight of infected mice was found. Histological examination of the liver revealed focal hepatitis. These signs of infection lasted from day 5 to day 14 after infection when mice slowly started to recover. Systemic treatment of MCMV-infected mice with thymic humoral factor (THF) resulted in a reconstitution of the mitogenic responses, IL-2 secretion, normalization of spleen weight and recovery of liver inflammation. Unlike other thymic hormones, THF did not affect interferon synthesis and NK cytotoxicity in infected mice. It is concluded that THF restores immune competence of mice immunosuppressed as a result of MCMV infection, through modulation of the T cell compartment.

Animals↗
PubMed1986

Effect of oral colchicine on T cell subsets, monocytes and concanavalin A-induced suppressor cell function in asthmatic patients.

Asthmatic patients have a deficiency of concanavalin A-(Con A) induced suppressor cell function. We tested whether oral colchicine 0.5 mg twice daily for 7 days could correct this immunoregulatory abnormality. Peripheral blood mononuclear cells were incubated with Con A and then suppression of proliferation was measured by coculture of these cells with healthy volunteers' mononuclear cells and phytohaemagglutinin. Sixteen asthmatic patients had significantly (P less than 0.002) decreased Con A-induced suppressor cell function (17.0 +/- 17.2%, mean +/- s.d.) as compared to 13 healthy volunteers (37.9 +/- 14.9%). Oral colchicine significantly (P less than 0.05) increased, though only partially corrected, these 16 asthmatic patients' Con A-induced suppressor cell function (28.1 +/- 14.3%). Asthmatic patients had an increased number of monocytes (691 +/- 289 vs 388 +/- 271/mm3 for normals, P less than 0.01) and a normal number of lymphocytes, Leu 4+ total T cells, Leu 3+ helper/inducer T cells, and Leu 2+ suppressor/cytotoxic T cells as well as a normal Leu 3/Leu 2 ratio. Oral colchicine significantly (P less than 0.005) decreased the number of monocytes (451 +/- 255/mm3) without significantly affecting the number of lymphocytes, Leu 4+, Leu 3+, or Leu 2+ T cells, or the Leu 3/Leu 2 ratio. These results are consistent with the hypothesis that the deficiency of Con A-induced suppressor cell function in asthmatic patients may be due, in part, to an increased number and/or abnormal activity of monocytes. If so, then oral colchicine may have partially corrected the deficiency of Con A-induced suppressor cell function by decreasing the number and/or modulating the activity of monocytes.

Adult↗
PubMed1986

Treatment of congenital immune deficiencies with a thymic hormone--thymic humoral factor.

Five infants with congenital immune defects are presented. Three had various combined immune deficiencies (CID) and two had thymic deficiencies only. As bone marrow or thymus transplantations were not feasible in these patients, we attempted treatment with thymic humoral factor (THF), a thymic hormone, by daily i.m. injections during biweekly courses. In one CID patient, a partial improvement in immune indices and temporary clinical improvement were achieved. In the other two, THF did not arrest the patients' demise. The two patients with thymic dysplasia benefitted repeatedly from THF treatment, as exemplified by the disappearance of wasting, diarrhea and infections and by reconstitution of T cell parameters. Nevertheless, the patients relapsed after prolonged periods without THF administration. We therefore propose the administration of long-term, continuous or intermittent thymic hormone replacement therapy in infants with congenital thymic defects. Early diagnosis and immediate institution of treatment will probably improve prognosis.

Female↗
PubMed1985

A mouse ear reaction for assessment of human lymphocyte immunocompetence.

A mouse ear reaction for testing cell mediated immunity of human lymphocytes using the local graft-versus-host reaction assay is described. Five million human mononuclears were locally injected into the ears of immune suppressed NZW mice. The reaction mounted was quantitated by determining the 125I-Iodo-Deoxyuridine (125I-UdR) incorporation in both ears. The ratio of 125I-UdR incorporation, of the injected to that of the non-injected ear (GVHR index), 7 days after lymphocyte injection, served as an accurate measure for the extent of the reaction. Only normal human mononuclears and purified, separated normal human T lymphocytes mounted a local graft-versus-host reaction. Whereas normal human B lymphocytes, chronic lymphatic leukemia B lymphocytes, mononuclears from patients with transitional cell carcinoma of the bladder, irradiated normal human mononuclears, mouse syngeneic mononuclears, or human erythrocytes gave no positive reaction. These experiments demonstrate that this assay can be used to quantitate an in-vivo specific graft-versus-host reaction.

Animals↗
PubMed1978

Adaptation of an Aedes aegypti mosquito cell line to growth at 15 degrees C and its response to infection by Sindbis virus.

Aedes aegypti mosquito cells, usually cultured at 28 to 30 degrees C, were adapted to grow at 15 degrees C. They were designated A. aegypti (c) cells, and had an estimated doubling time of 10 days. Sindbis virus (SV) replicated in these cells to peak titres of over 1.0 x 10(9) p.f.u./ml 8 to 10 days after inoculation. These, or about 10-fold lower titres, continued to be produced over a 130 day test period without causing visible cell damage. Continuous virus proliferation and the yield of uniformly large plaque forming progeny viruses are the two most important features which differentiate infection with this virus in A. aegypti (c) cells from that of A. aegypti cells grown at 28 degrees C (Peleg & Stollar, 1974). Absence of homologous interference vis-à-vis cell-virus coexistence suggests that homologous interference is not a prerequisite for maintaining cell-virus coexistence. Preinoculation of A. aegypti (c) cultures with a small plaque forming Sindbis virus (SV-S) leads, under certain conditions, to the establishment of homologous interference.

Adaptation, Biological↗
PubMedDate not supplied

Immune features in complete Freund adjuvant-treated CBA/J mouse model.

Immunostimulation with complete Freund adjuvant (CFA) reverses the tendency to fetal loss in the CBA/J x DBA/2J mouse. First attempts to understand the mechanisms underlying this effect were to evaluate phenotypic and functional changes in the lymphocytic cell population after immunopotentiation. We demonstrated that treatment with CFA leads to diminished responses of maternal splenocytes towards paternal alloantigens and this low response cannot be improved with exogenous interleukin-2. Lymphocytes derived from spleen, para-aortic draining lymph nodes and placenta significantly suppress maternal response to paternal antigens. The effect of low fetal resorption rate is followed by marked elevation of asialo GM-1 and HNK-1-positive cells but not followed by any change of the L3T4 or Lyt-2-positive lymphocyte population in either the spleen or in draining lymph nodes. L3T4 and Lyt-2-positive cells have not been found in the placenta. An important feature was marked elevation of Mac-1-positive cells in the placentas of CFA-treated animals. The relevance of these findings to CFA-induced fetal protection is still under investigation.

Animals↗
PubMedDate not supplied

Immunocompetence status as related to growth progression of mouse MOPC-315 plasmacytoma.

The immunocompetence status of mice bearing MOPC-315 plasmacytoma was determined at various days after tumor inoculation. Changes in T and B-cell functions appeared gradually. The allogeneic response of spleen cells from BALB/c tumor-bearing mice against C57BL spleen cells was impaired from the 4th day after the tumor inoculation (nonpalpable tumor stage). The primary antibody response in vitro against SRBC was depressed at 18 days, and the mitogenic response of splenic cells to PHA and to LPS was depressed at 25 days after the tumor inoculation. T cells taken from day 18 tumor-bearing mice partially suppressed the MLR response of normal splenocytes. Mice bearing large MOPC-315 tumors responded less to SRBC immunization than normal, noninoculated mice. The relative percentage of Lyt 1, Lyt 2 and L3T4 T-cell subsets decreased starting from the 11th day after tumor inoculation.

Animals↗