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Biomedical subjects

A Klajman

Publications and source records attributed to A Klajman.

At least 19 recordsLinked to original sources
PubMed1991

Appearance of the T-cell marker CD8 on B chronic lymphatic leukemia cells in long-term cultures.

Long-term cultures of highly purified B chronic lymphatic leukemia cells (B-CLL), were established. The B-CLL lymphocytes acquired the CD8 T cell marker in long-term cultures while still retaining their surface immunoglobulins. In confirmation of previous results, the cultured B-CLL lymphocytes released factor(s) into the culture medium that suppressed the allogeneic mixed-lymphocyte reaction. No correlation was found between the appearance of the CD8 T cell surface marker and onset of suppressor activity.

Antigens, Surface↗
PubMed1989

Inhibition of delayed hypersensitivity reactions in mice by colchicine. I. Mechanism of inhibition of contact sensitivity in vivo.

Colchicine has been recently shown to inhibit delayed hypersensitivity reactions (DHR). In the present study we investigated the effects of colchicine on contact sensitivity (CS) to dinitrofluorobenzene. Colchicine, at a dosage level of 15 micrograms/mouse, inhibited the elicitation of the contact response only when given on the day of ear challenge. Administration of the drug during the induction phase did not have any effect on the CS reaction. By using adoptive transfer experiments, we could demonstrate that CS was suppressed only when colchicine was given to the recipient mice, while treating the donors of immune lymph node cells (I-LNC) did not affect their ability to transfer a significant DHR. These findings were observed also when I-LNC were directly injected into the ears, a result which indicated that there was no effect of the drug on the ability of effector cells to migrate to the site of antigen challenge. Neither was there any effect on the distribution of T cell subsets in peripheral lymph nodes. The proliferative response of LNC to antigenic or mitogenic stimulation in vivo or in vitro was also not affected by colchicine pretreatment. These findings raise major questions about the mechanism of action of colchicine in vivo and suggest that more experimentation is required to probe the mechanism of colchicine-induced suppression of DHR.

Animals↗
PubMed1988

Malignant thymoma with peripheral blood lymphocytosis.

A 37-year-old woman with a giant, lymphocytic predominant thymoma involving the pleura and accompanied by a sharp peripheral blood lymphocytosis is described. Only electromicroscopic and immunohistologic studies could exclude the alternative diagnosis of mediastinal lymphoma. The tumor and peripheral blood lymphocytes were characterized as T4 lymphocytes. The thymoma responded very well to a combination of radiation and cytotoxic therapy. Forty-two months after diagnosis, the patient is still is complete remission.

Adult↗
PubMed1988

Chronic lymphocytic leukemic (CLL) cells secrete multispecific autoantibodies.

A subset of B cells expressing the CD5 marker, a 67 KD molecule, has been implicated in the pathogenesis of autoimmune disease. To study the immunoglobulin repertoire of CD5+ B cells we investigated chronic lymphocytic leukemic (CLL) cells, since the majority of the malignant clones express CD5. CLL were induced to secrete their IgM in vitro by phorbol 12-myristate 13-acetate (PMA) and the supernatants screened for binding to a panel of autoantigens. Twelve out of 14 CLL clones were autoreactive, binding to Fc of IgG, ssDNA, dsDNA, histones, cardiolipin, or cytoskeletal components. Many also bound to more than one antigen tested for, showing multispecificity. Our data suggest that a high proportion of CD5+ B cells are programmed to secrete multispecific autoantibodies.

Antibodies, Neoplasm↗
PubMed1988

Changes in lymphocyte subpopulations in peripheral blood of splenectomized patients.

Twenty-five patients who had undergone splenectomy were investigated. Splenectomy was performed in 16 patients because of traumatic rupture of the spleen, in 6 due to idiopathic thrombocytopenic purpura (ITP) and in 3 because of other causes. The absolute numbers of T-cell subclasses--helper/inducer (CD4+) and suppressor/cytotoxic (CD8+)--and of B-cells were determined in peripheral blood. The CD4+/CD8+ was decreased in 7 patients and inverted in 10. The change in the ratio was not due to a decreased number of CD4+ cells but to an increase of CD8+ cells. Sex, age, and the time at which splenectomy was performed bore no relation to the CD4+/CD8+ ratio. In 13 of the 25 patients a significant increase in the number of polyclonal B-cells was found. None of the patients had severe infections. These observations suggest that splenectomy is responsible for the change in the CD4+/CD8+ ratio. Susceptibility to infections seems to correlate with the absolute decrease of CD4+ cells rather than with the change of the ratio.

Adolescent↗
PubMed1987

Augmentation of mitogen responsiveness in the aged by a special lipid diet AL 721.

Diminished immune responses in aging may be partially due to alteration of the lipid composition of membrane and a decrease in membrane fluidity. The effect of a daily diet of 10 g active lipid (AL 721) on the mitogen responsiveness of peripheral blood mononuclear cells (PBMC) from aged volunteers was studied. AL 721 is a mixture of lipids from hen egg yolk which was formulated for in vivo rectification of rigidified cell membranes in an attempt to restore proper physiological function. After 3 weeks on the diet, six aged participants displayed a significant increase in lymphocyte responsiveness to mitogens, while in four the responsiveness was unaffected, or increased insignificantly. In all six participants, a decline in lymphocyte responsiveness was observed a week after termination of the diet. Our preliminary results indicate that improvement of immune functions in the aged may be achieved by dietary manipulation of lipids. This innocuous approach seems to be of potential value and merits further studies.

Aged↗
PubMed1987

Functional analysis of mononuclear cells infiltrating into tumors: lysis of autologous human tumor cells by cultured infiltrating lymphocytes.

Lymphocytes separated from surgically resected tumor tissue, uninvolved lung tissue, and peripheral blood of lung cancer patients were investigated for cytotoxic potential and analyzed for their phenotypes at the time of surgery and after having been propagated for 4 to 5 wk in the presence of interleukin-2. Most of the tumor lymphocyte infiltrates examined were shown to have a shift in favor of T8 subsets from those found in peripheral blood. No natural killer activity and low cytotoxicity against the autologous tumor were found to characterize the tumor-derived lymphocyte population. Propagation of lymphocytes from the different tissues of the cancer patient in the presence of interleukin-2 preparation induced widespread lytic activity against K562 cells, autologous and allogeneic tumors, but not autologous normal lung or lymphoblasts. However, cytotoxic activity against autologous tumor cells exerted by cultured tumor-infiltrating lymphocytes was found to be significantly higher than the activity of cultured lymphocytes isolated from peripheral blood or uninvolved lung tissue of the same patient. The elevated lytic activity of cells derived from the tumor tissue indicates the accumulation at the tumor site of precursors of natural killer-like cells and specifically stimulated antitumor effectors. Our results suggest the coexistence of two types of anti-autotumor cytotoxic lymphocytes at the tumor site: natural killer-like and specific cytotoxic T-cells.

Aged↗
PubMed1987

Detection of antibodies to total histones and their subfractions in systemic lupus erythematosus patients and their asymptomatic relatives.

Sera drawn from 75 patients with systemic lupus erythematosus, 141 healthy relatives (from the families of 51 patients), and 115 healthy control subjects were examined, by enzyme-linked immunosorbent assay, for IgG and IgM antibodies to total histones and their subfractions. Compared with the controls, statistically significant numbers of patients and their relatives had antihistone antibodies of both isotypes. Among the relatives, the sera from females, notably sisters of the patients, contained the highest levels of anti-total histone antibody. Anti-H2A/H2B and H3 antibodies were most prevalent among the lupus patients, but many of the relatives had IgM anti-H4 antibodies. These findings indicate that antihistone antibodies can serve as a genetic marker in patients with systemic lupus erythematosus.

Autoantibodies↗
PubMed1987

Increased presence of common systemic lupus erythematosus (SLE) anti-DNA idiotypes (16/6 Id, 32/15 Id) is induced by procainamide.

Sixty-seven patients on treatment with procainamide were examined for the presence of two common idiotypes of anti-DNA antibodies (16/6 Id and 32/15 Id). These idiotypes have been shown previously to have clinical relevance in patients with systemic lupus erythematosus (SLE). An enzyme-linked immunosorbent assay (ELISA) with rabbit anti-Id antibodies revealed increased concentrations of the 16/6 Id and 32/15 Id in 25 (37%) and 16 (24%) patients, respectively. Five of eight patients with drug-induced lupus had elevated titers of both idiotypes. A high correlation (R = 0.56, P less than 0.001 for 16/6 Id) was found between Id levels and anti-single-stranded DNA (ssDNA) antibody titers and between 16/6 Id titers and antihistone antibodies (IgG, R = 0.43; IgM, R = 0.25). It seems that procainamide, a component known to be associated with drug-induced lupus, may induce an increased production of common anti-DNA idiotypes in apparently normal subjects.

Antibodies, Viral↗
PubMed1987

Clonal analysis of human tumor infiltrating lymphocytes reactive with autologous tumor cells: different target cell specificities of NK-like and cytotoxic T-cell clones.

Lymphocytes, derived from surgically resected lung carcinoid tissue, were stimulated in mixed culture with irradiated autologous tumor cells (MLTC). The autologous MLTC-stimulated lymphocytes were found to have killing activity against both autologous tumor cells and NK-sensitive target cells. The lymphoblasts generated during MLTC were isolated and cloned under limiting dilution conditions in the presence of interleukin 2. The cloned cell lines were analyzed for cell phenotype and tested for cytotoxic activity. Three cloned cell lines, out of 19 tested, were found to be cytotoxic either against NK-sensitive target cells (natural killers) or the autologous tumor cells. Two clones, having OKT8 phenotype, caused no lysis of the autologous tumor cells, though both exerted NK-like activity against K562 cells. Only one clone with OKT4 phenotype showed specific cytotoxic activity against the autologous tumor, but no NK-like activity against a panel of tumor target cells. These results suggest the coexistence of two types of antitumor cytotoxic lymphocytes at the tumor site: precursors of NK-like cells and specific cytotoxic T cells. Target cell specificity provided a means of distinguishing between the two types.

Aged↗
PubMed1987

Long-term cultures of chronic lymphocytic leukemia B cells generate B suppressor cells.

B suppressor cells (Bs) were generated by stimulation with PHA-P or concanavalin A of B cells from peripheral blood of B-cell chronic lymphocytic leukemia (B-CLL) patients. They suppressed well allogeneic mixed lymphocyte reactions. Long-term colonies of B cells from B-CLL were established for up to 6 weeks in liquid media, with B cells acquiring properties of suppressor cells while being cultured. Two types of cultures were observed: cells either grew in compact multicellular colonies or formed diffuse monolayers. Cells that remained alive in cultures for a number of weeks, but did not multiply, did not develop suppressive characteristics. Bs cells retained their phenotypic markers in cultures. Mitosis and lymphoblasts, but no differentiation into plasma cells, were observed. PHA-P-generated Bs were cultured in long-term colonies, retaining their suppressor properties. The establishment of long-term cultures of B-CLL cells may facilitate a better understanding of the nature and characteristics of normal and leukemic B cells.

Aged↗
PubMed1987

Human muscle-derived, tissue specific, myocytotoxic T cell lines in dermatomyositis.

Mononuclear cells were isolated from the inflamed muscle tissue of a patient suffering from dermatomyositis (DM). These were expanded in long-term culture and maintained in the presence of IL-2 containing culture medium. Two cell lines were established, one of the helper/inducer (OKT4+) and the other of the suppressor/cytotoxic phenotype (OKT8+). The OKT4+ cell line exhibited a non HLA-restricted, tissue-specific, myocytotoxic effect on rat muscle cell culture. Its lymphoproliferative response to human muscle antigen was HLA-restricted. The OKT8+ cell line exhibited a non HLA-restricted, tissue-specific response to muscle antigens and no myocytotoxic activity in in vitro rat muscle cell culture. It is likely that clones of OKT4+ lymphocytes in patients suffering from DM are associated with the pathogenesis of the disease--they probably mediate the diffuse damage to skeletal muscle through their myocytotoxic activity.

Aged↗
PubMed1987

Stevens-Johnson syndrome associated with Mycoplasma pneumoniae infection.

The Stevens-Johnson syndrome is a relatively uncommon, severe form of erythema multiforme. A case is presented in which Mycoplasma pneumoniae infection was established as the causative agent. Clinicians need to be aware of this uncommon association. We emphasize the need to consider M. pneumoniae infection as one of the many agents responsible for the Stevens-Johnson syndrome.

Adolescent↗
PubMed1986

T lymphocytes of rheumatoid arthritis patients show augmented reactivity to a fraction of mycobacteria cross-reactive with cartilage.

An acetone-precipitable fraction of Mycobacterium tuberculosis cross-reacts with human cartilage. Immune responses to this antigen were assessed in 34 patients with rheumatoid arthritis, 16 patients with degenerative joint disease, and 15 healthy controls. The RA patients differed from the other two groups in having more pronounced T lymphocyte responses to the antigen; their serum antibody levels were not higher. The responses of RA patients varied with duration of disease. In the first year (7 patients) T lymphocyte reactivity was increased in the synovial exudates of affected joints but not in peripheral blood, whereas the 19 with disease of 1-10 years' duration showed high reactivity in peripheral blood; in the 8 with disease for more than 10 years, lymphocyte reactivity did not differ from that in the patients with degenerative joint disease or the healthy controls. The observation that the three groups did not differ in their responses to streptococci and a T-cell mitogen indicates that reactivity of the RA patients to the mycobacterial fraction was specific. These results raise the possibility that bacterial antigens cross-reactive with cartilage proteoglycans may be relevant to the pathogenesis of RA.

Adult↗