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Biomedical subjects

J Wasserman

Publications and source records attributed to J Wasserman.

At least 55 records · Page 3Linked to original sources
PubMed1988

Decreased blood natural killer cell activity and immunoglobulin synthesis in vitro in aplastic anemia.

Natural killer (NK) cell numbers and T lymphocyte subpopulations in peripheral blood were evaluated in six patients with aplastic anemia (AA). The immunophenotyping results were correlated to in vitro tests of NK cell cytotoxicity against K562 cells and of immunoglobulin (Ig) production after pokeweed mitogen (PWM) stimulation. A significant decrease was found both in the percentage of Leu 11 positive cells and in NK cell activity as compared to age- and sex-matched healthy controls. The decrease in NK cell activity could not be entirely compensated by an increase in effector/target cell ratios, thus suggesting not only a quantitative but also a functional defect in NK cells of the AA patients. Three of four AA patients tested showed no major increase of Ig production after PWM stimulation. All these three patients also had fewer "functional T helper" cells (Leu3+/Leu8-) and increased numbers of T suppressor/cytotoxic cells (Leu2+) when compared to controls. No significant differences in numbers of B lymphocytes (B1+) could be found. Our findings suggest a possible linkage between quantitative and qualitative abnormalities in lymphocyte subsets in aplastic anemia. However, no evidence was found to support the hypothesis of increased NK cell activation behind the hemopoietic depression in this disease.

Adolescent↗
PubMed1988

Resistance of some leukemic blasts to lysis by lymphokine activated killer (LAK) cells.

Peripheral blood mononuclear cells (PBMC) from healthy donors and AML patients in remission were stimulated with phytohemagglutinin (PHA) and recombinant interleukin-2 (IL-2). These stimulated cells (lymphokine activated killer (LAK) cells) showed increased DNA synthesis as measured by 3H-Thymidine uptake. A synergistic effect of PHA and IL-2 was found. LAK cells' ability to kill acute myeloid leukemia (AML) blasts was investigated by the 51Cr release assay. LAK cells showed a cytotoxicity (over 10% specific 51Cr release) against 9/12 leukemic blasts, even at effector/target (E/T) ratios as low as 5:1. However, on average only 22.2% (SD 11.8) and 36.5% (SD 12.5) 51Cr release were obtained in 4- and 18-hour cytotoxicity assays, respectively, at an E/T ratio of 20:1. Leukemic blasts in 3/12 AML cases and normal PBMC were entirely resistant to lysis, even at an E/T ratio of 80:1. Susceptibility to lysis was not correlated to peanut-agglutinin receptor expression. LAK cells were more cytotoxic towards the K-562 cell line (natural killer activity) than unstimulated PBMC.

Cell Line↗
PubMed1988

Synergistic enhancement of mitogen responses of human lymphocytes by inhibitors of cyclo-oxygenase and lipoxygenase.

Previously we reported that inhibitors of the enzyme cyclo-oxygenase, which reduce biosynthesis of prostaglandins, may enhance mitogenic responses of human blood lymphoid cells, whereas only marginal effects were observed with 5,8,11-eicosatriynoic acid (ETI), which inhibits 12-lipoxygenase and leukotriene biosynthesis. However, sharply enhanced mitogen responses were observed when lymphoid cells were cultured with both a cyclo-oxygenase inhibitor and ETI, suggesting a synergy between the two drugs. To test whether this is a more general phenomenon occurring between inhibitors of cyclo-oxygenase and lipoxygenase, we have now extended these studies to include the following lipoxygenase inhibitors: cirsiliol; esculetin; 5,8,11,14-eicosatetraynoic acid, and nordihydroguaiaretic acid. The results have shown that any of these drugs combined with a cyclo-oxygenase inhibitor may enhance mitogen responses more than one would expect by summing the effects of the inhibitors tested separately. We conclude that inhibitors of cyclo-oxygenase and lipoxygenase may synergistically enhance mitogen responses of lymphoid cells.

Arachidonate Lipoxygenases↗
PubMed1988

Modulation of lymphocyte and monocyte responses in vitro by 9-deoxy-delta 9-prostaglandin D2 and 9-deoxy-delta 9-delta 12-prostaglandin D2.

The effects of 9-deoxy-delta 9-prostaglandin D2 (PGJ2) and 9-deoxy-delta 9-delta 12-prostaglandin D2 (delta 12PGJ2), which are metabolites of PGD2, on lymphocyte and monocyte reactions were studied in vitro. Expression of various phenotypic markers of lymphocyte subsets, as detected by monoclonal antibodies, was not affected by overnight incubation in 3 x 10(-5) M PGJ2. Phytohemagglutinin stimulation and natural killer activity of lymphocytes was reduced by PGJ2 and delta 12 PGJ2. Monocyte reactivity to 12-o-tetradecanoylphorbol-13-acetate, as assessed by chemiluminescence, was stimulated by preincubation of the cells for 1 h in 3 x 10(-5) M PGJ2 or delta 12 PGJ2. Such an augmentation was not exerted by PGD2.

Adjuvants, Immunologic↗
PubMed1988

Dermatophytosis and HIV infection. A study in homosexual men.

Mycological and clinical investigations were carried out in 193 homosexual men, 83 of whom had HIV antibodies, and 117 heterosexual men. Dermatophytes were recovered from the feet in 37.3% of HIV seropositive homosexual men, 31.8% of seronegative homosexual men and 8.6% of heterosexual men. Tinea pedis in homosexual men was significantly more common with increasing age. There was an increased number of sexual partners in the group of homosexual men with tinea pedis. Two dermatophytes were recovered from single samples in 14.5% of homosexual men with dermatophytosis. Dermatophytes were occasionally isolated from clinically normal toe clefts. Present results point to the importance of dermatophytes in nail dystrophy affecting patients with advanced HIV infection. Dermatophytosis in homosexual men was not associated with any changes in counts of blood T lymphocyte subsets or skin reactivity to tuberculin.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Effect of phytohemagglutinin and interleukin-2 on malignant and nonmalignant B and T lymphocytes.

Peripheral blood mononuclear cells (PBMC) from patients with acute myeloid leukemia (AML) or non-Hodgkin lymphoma (NHL) and healthy controls were stimulated with phytohemagglutinin (PHA) and interleukin-2 (IL-2). PHA (1 microgram/ml) induced higher 3H-thymidine incorporation than 800 U/ml IL-2 in PBMC from both controls and patients with AML in complete remission. A synergistic effect between PHA and IL-2 was found. Malignant B cells from 5/12 NHL expressed IL-2 receptors and showed proliferative response to IL-2, but not to PHA. PHA induced higher cytotoxicity toward AML blasts in lymphocytes from healthy controls than did IL-2. In addition, PHA induced higher cytotoxicity in lymphocytes from healthy controls than in those from patients with AML in remission. In contrast, no difference in cytotoxicity between controls' and patients' lymphocytes was found after stimulation with IL-2. No HLA restriction could be demonstrated. Normal peripheral blood mononuclear cells and leukemic blasts from 2/12 AML were completely resistant to cytotoxic cells even at effector:target ratios four times as high as those otherwise required.

B-Lymphocytes↗
PubMed1987

Influence of alpha-interferon therapy on blood lymphoid cells. Studies on antibody production, mixed lymphocyte culture response, mitogen responsiveness and 2'-5'oligoadenylate synthetase activity.

The influence of natural alpha-interferon (alpha-IFN) therapy (3 X 10(6) units i.m. daily) on blood lymphoid cells was studied in 20 patients with gynecological neoplasias (7 patients with condylomata accuminata and 13 patients with ovarian carcinoma). There was a statistically significant increase in the intracellular levels of 2'-5'oligoadenylate synthetase 1 day after the first injection of IFN and with few exceptions this activity remained increased during 3 months of treatment. In most of the patients, the capacity of blood lymphoid cells to produce IgA, IgG, and IgM following stimulation with pokeweed mitogen was decreased 1 day after the first injection of IFN and with few exceptions it remained low during 6 months of IFN therapy. In most patients there was a decrease in the capacity of lymphoid cells to act as stimulator or responder cells in a mixed lymphocyte culture during IFN therapy. The alpha-IFN therapy had no major influence on the response of lymphoid cells to mitogens. We conclude, that neither this nor our previous studies on the influence of IFN therapy on immunological functions have given support to the hypothesis that the antitumor action of IFN is mediated by the immune system.

2',5'-Oligoadenylate Synthetase↗
PubMed1987

Changes of the blood lymphocyte population following 131I treatment for nodular goiter.

The blood lymphocyte population was examined in 34 patients who were treated with 131I for toxic or atoxic nodular goiter. The patients received one to three doses of 300-550 MBq of 131I administered at 1 week intervals. Lymphocyte counts were significantly reduced both 1 and 6 weeks after treatment. This reduction was accompanied by a changed composition of the lymphocyte population. The frequency of lymphocytes expressing membrane receptors for C'3 (EAC-rosette forming) was significantly reduced 1 and 6 weeks after 131I-administration. At 6 weeks there was a slight but statistically significant increase of the frequency of T-cells as identified by Leu 1 monoclonal antibodies. This was largely caused by an increased proportion of helper/induced T-cells as identified by Leu 3a monoclonals. 131I-treatment also reduced the capacity of lymphocytes to secrete immunoglobulins (Ig) upon PWM-stimulation. The most pronounced effect was observed for IgM. Secretion of IgG and IgA were less reduced. Mitogenic stimulations of lymphocytes with PHA and ConA were not significantly changed. We conclude that these changes observed, with the exception of mitogen reactivity, are essentially similar to those occurring after external radiation therapy for cancer. We speculate that blood lymphocytes passing through the continuously irradiated gland are damaged mainly by emitted beta-particles.

Adult↗
PubMed1987

Effect of 32P treatment for polycythaemia vera on blood lymphocyte subpopulations and their functions.

The influence of 32P treatment on the blood lymphocyte population was examined in 16 patients with polycythaemia vera who had not previously been treated with cytotoxic drugs or irradiation. Before treatment the lymphocyte counts were within the normal range but the expression of certain membrane structures, as detected by monoclonal antibodies directed against total T cells (CD 3 and 5), helper/inducer (CD 4) and suppressor/cytotoxic T cells (CD 8), were slightly reduced. In addition, mitogenic responses of the lymphocytes to PHA and PWM-induced Ig secretion were severely impaired. Following a single oral dose of 32P (150-305 MBq), which was shown to normalize the production of erythrocytes and/or platelets, the blood lymphocyte counts were reduced by approximately 40% 12 wk after treatment. Subset analysis showed that the proportion of B cells, as identified by monoclonal antibodies (CD 20), was reduced to the highest relative extent. On the other hand, lymphocytes expressing the above T cell markers were somewhat increased. 32P treatment sharply increased PHA reactivity but it further reduced PWM-induced Ig secretion. The latter observation was in line with the finding that serum concentrations of Ig were reduced following treatment.

Aged↗
PubMed1987

Synergistic enhancement of mitogen responses of human lymphocytes by inhibitors of cyclo-oxygenase and 5,8,11-eicosatriynoic acid, an inhibitor of 12-lipoxygenase and leukotriene biosynthesis.

Blood mononuclear cells are well-known producers of various cyclo-oxygenase and lipoxygenase metabolites of arachidonic acid, some of which possess immunoregulatory functions. In the present investigation, we have examined 3H-thymidine incorporation in human blood lymphocytes cultured with polyclonal mitogens and antigens in the presence of various inhibitors of cyclo-oxygenase (such as indomethacin and meclofenamic acid) and an inhibitor of 12-lipoxygenase and leukotriene biosynthesis, 5,8,11-eicosatriynoic acid (ETI). It was observed that these inhibitors could augment mitogen responses of nonpurified lymphocyte preparations but not of preparations which were depleted of monocytes. The results indicate that monocytes and not lymphocytes were the main producers of immunosuppressive eicosanoids derived from arachidonic acid. Further, mitogenic responses in the presence of both an inhibitor of cyclo-oxygenase and ETI were augmented to a higher extent than expected. Again, this enhancement was not observed in preparations depleted of monocytes. Arachidonic acid metabolism was examined in mitogen-stimulated cultures pulsed with 14C-arachidonic acid. It was observed that the production of three metabolites was inhibited by meclofenamic acid, whereas the amounts of another 14Cr-labeled compound were almost doubled in the presence of meclofenamic acid.

8,11,14-Eicosatrienoic Acid↗
PubMed1987

Effects of some prostaglandins and leukotrienes on lymphocytes, monocytes and their activity in vitro.

The effect of some prostaglandins (PGs) and leukotrienes (LTs) on lymphocytes and monocytes was tested in vitro. Overnight incubation with PGD2 reduces the expression of Leu-2 antigen (suppressor/cytotoxic phenotype) and of Fc receptors for IgG. PGA2, PGD2 and to a lesser extent PGE2 inhibit PHA reactivity of lymphocytes. LTB4 does not have any inhibitory activity. Preincubation of lymphocytes with PGD2 and PGE2 decreases their NK activity. LTB4, but not the PGs tested, stimulates monocyte metabolism as assessed by chemiluminescence.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1987

Oral candida albicans in HIV infection.

The prevalence of oral colonization with Candida albicans was studied in 225 homosexual men, 99 of whom had HIV antibodies and in 175 heterosexual men. Oral candidal carriage was most prevalent among HIV seropositive homosexual men (77.8%). Rich growth of C. albicans in culture and findings of pseudomycelial elements in oral mucosal smear also correlated with HIV seropositivity. Pseudomycelial forms of C. albicans were demonstrated in mucosal smear from all patients with oral mucosal lesions suspected for candidiasis. However, 26/53 patients (49.1%) with positive smear had no clinical signs of oral candidiasis. The oral yeast flora was sampled twice in 85 homosexual men at an interval of 12-18 months. 71/85 patients (83.5%) were grouped into the same category of candidal colonization; carrier or noncarrier state, on both occasions. No statistically significant differences in numbers of CD 4 cells or CD 8 cells were observed between patients with respect to candidal colonization, when HIV seropositive and seronegative homosexual men were considered separately.

AIDS-Related Complex↗
PubMed1987

Incidence of infectious symptoms after radiation therapy for breast cancer. Long-term effects.

The incidence of symptoms generally associated with infectious disease was assessed by a questionnaire sent out to 519 disease-free breast cancer patients 7 to 12 years after primary treatment. All patients were treated in the context of a randomized trial where pre- and postoperative radiation (45 Gy) was evaluated versus surgery only. The results indicate a significantly higher morbidity among patients treated with preoperative irradiation compared with those irradiated postoperative (p less than 0.05). This increased morbidity mainly seemed to be caused by symptoms usually associated with respiratory tract infection (p less than 0.05). Although statistically not significant the preoperatively irradiated patients also had a higher morbidity than those treated with surgery alone. There was no difference between postoperatively irradiated patients and patients treated with surgery only. A significantly higher integral dose (absorbed energy within the body) of the pre- compared with the postoperative group (p less than 0.025) is associated with the differences in morbidity between the two irradiated groups. An explanation for the increased morbidity seems to be that the volume of lung tissue, encompassed within the full-dose target volume, is the crucial factor. This volume was considerable in the preoperatively treated patients but kept at a minimum in the postoperative group.

Adult↗
PubMed1987

Purified trichophytin: lymphocyte reactivity in vitro and trichophytin-induced suppression.

Three trichophytin preparations from different strains of Trichophyton mentagrophytes were produced according to the ethylene glycol method and assessed for their lymphocyte stimulation activity in vitro (LST). These trichophytin preparations showed significant variations in their effects on cord lymphocytes reactivity. The preparations also varied in their stimulation of lymphocytes from patients with dermatophytosis. Conclusions could be drawn about the immunological specificity, sensitivity and lymphocyte toxicity, which is important for the standardization of antigens. Furthermore, it was demonstrated that trichophytin-preincubated lymphocytes mediated a suppression of lymphocyte reactivity to this antigen.

Adult↗
PubMed1986

Prognostic relevance of postirradiation lymphocyte reactivity in breast cancer patients.

The prognostic relevance of phytohemagglutinin (PHA) and purified protein derivative (PPD) lymphocyte reactivity at diagnosis and after radiotherapy was evaluated in breast cancer patients. The patients were followed up to 13 years and the prognostic value expressed as ratios between observed number of deaths and "estimated" number of deaths under the null hypothesis. There was no significant association between the initial PHA and PPD reactivity and the survival of the patients. On the other hand, mortality up to 8 years after radiotherapy was significantly higher for patients with low PHA and PPD reactivity at completion of treatment. Furthermore, patients who had higher than average PPD reactivity 6 to 10 months after radiotherapy, seemed to have a higher survival rate. The prognostic relevance of postirradiation lymphocyte reactivity was only to some extent explained by clinical stage.

Breast Neoplasms↗