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Biomedical subjects

J Wasserman

Publications and source records attributed to J Wasserman.

At least 19 recordsLinked to original sources

Single-view screening mammography: psychological, endocrine and immunological effects of recalling for a complete three-view examination.

To investigate influences of a recall due to inconclusive findings on screening mammography, 45 women were examined with psychological ('mood' and 'coping'), endocrine and immunological tests immediately after complete mammography (first interview), 2-3 days after the initial screening mammography, and 3 weeks after the women had been informed of normal findings (second interview). The mood score in the first interview was significantly lower than in the second. No differences were found in the endocrine and immunological tests. The recall for complete mammography provoked a significant short-term emotional reaction not reflected in changes in the endocrine and immune functions.

Affect

Indomethacin modulation of monocyte cytokine release following pelvic irradiation for cancer.

Pelvic irradiation for urogenital cancer reduced monocyte release of tumour necrosis factor alpha (TNF-alpha). Addition of indomethacin to monocyte cultures increased TNF-alpha production after but not before irradiation. E. coli lipopolysaccharide (LPS) increased TNF-alpha release before as well as after radiation therapy and addition of indomethacin to LPS-stimulated monocytes further increased TNF-alpha production following radiotherapy. Spontaneous interleukin-1 (IL-1) release was increased in the cancer patients and was not significantly affected by radiation therapy. LPS increased IL-1 release before as well as after irradiation, but indomethacin did not further change IL-1 secretion. These findings suggest that prostaglandins differentially regulate TNF-alpha and IL-1 release. Administration of cyclo-oxygenase inhibitors during radiation therapy might increase TNF-alpha release in vivo and thereby enhance the host defence against tumours.

Aged

Influence of interferon on antibody production and viability of malignant cells from patients with multiple myeloma.

The influence of interferon (IFN) on antibody production and viability of malignant cells from patients with multiple myeloma was evaluated. Following incubation of bone marrow cells with IFN-alpha (5000 units/ml) for 7 days) a decreased production of monoclonal immunoglobin (mlg) was detected in all experiments except one. IFN induced a greater than 50% decrease in myeloma cell viability in 11 patients and a greater than or equal to 25% decrease in 4 patients, whereas in myeloma cells from 8 patients IFN had no or only minor effects. The observed effect was not due to an inhibition of proliferation since less than 5% of the myeloma cells were labeled with [3H]-thymidine during 7 d of culture. There was no statistically significant correlation between decreases in myeloma cell viability and effects on mlg production, exemplified by the fact that mlg production was decreased also in patients showing no sensitivity to IFN's cytotoxic action. Depletion of autologous T-cells, NK-cells and/or monocytes did not abrogate the effects observed. We conclude that IFN can reduce the viability of myeloma cells and the production of Ig from these cells and that the latter can be exerted without an antitumor effect.

Antibody Formation

Neuroendocrine and immunologic effects of unemployment and job insecurity.

We prospectively followed a cohort of 354 blue-collar men and women, some of whom lost their jobs. Results show marked effects during the anticipatory and early unemployment phase on mental well-being, serum cortisol, prolactin, total cholesterol, HDL cholesterol, and phytohemagglutinin reactivity of lymphocytes. Most of these changes appear to be of short-term duration. However, changes in cardiovascular risk factors are observed at least 2 years following the loss of one's job. Coping style appears to be a major determinant whether or not and how people will react to unemployment.

Adaptation, Psychological

Blood lymphocyte population following 131I treatment for hyperthyroidism.

A number of immunological parameters have been monitored for up to 6 weeks following 131I treatment for hyperthyroidism in Graves' disease. The aim was to examine whether this isotope treatment normalizes or further accentuates some immunological abnormalities which may be a manifestation of autoimmune reactions in these patients. It was confirmed that both the cellular composition and immunological reactivities of the patients' blood lymphocytes were abnormal before treatment. After 131I administration a slight lymphopenia occurred and the ratio between CD4 and CD8 positive T lymphocytes (helper-inducer/suppressor-cytotoxic), which was increased before treatment, increased further. Moreover, PWM-triggered IgM secretion in vitro was reduced by 50%. No other immunological parameters studied, such as secretion of other Ig classes, mitogenic responses of lymphocytes, and distribution of other lymphocyte subsets, changed to any detectable extent. It remains speculative whether the 131I-induced changes of the immune system may further accelerate the underlying autoimmune disease processes.

Adult

Evaluation of the fluorescent treponemal antibody-absorption (FTA-Abs) test specificity.

Serum samples from 43 patients with positive test for syphilis only in the FTA-Abs test, were evaluated. Three had primary or treated syphilis. Twenty-one (49%) had clinical and/or serological signs of Lyme borreliosis as assessed by whole-cell sonicate Borrelia burgdorferi ELISA and Western blot techniques. Seven (16%) had genital Herpes simplex infection and the remaining 12 patients, miscellaneous disorders. In control sera from 30 patients with Lyme borreliosis an isolated positive FTA-Abs reaction was found in 13 patients (43%). Elevated Borrelia ELISA titres were found in nine of 30 (30%) syphilitic patient serum samples, whereas Western blots for Borrelia were negative. Six per cent of healthy blood donors were seropositive for Borrelia. Lyme borreliosis is an important cause of cross-reactions in the FTA-Abs test. Other serological tests for syphilis and Western blot for Borrelia are useful for discrimination.

Adolescent

In vitro capacity of various cyclooxygenase inhibitors to revert immune suppression caused by radiation therapy for breast cancer.

Radiation therapy triggers blood monocytes to an increased secretion of immunosuppressive prostaglandins (PGs), which in part can explain the post-irradiation impairment of lymphocyte blastogenesis. Since low mitogen responses of lymphocytes in irradiated breast cancer patients is linked to a poor prognosis a clinical trial is planned to examine if treatment with inhibitors of PG-synthesis during irradiation can counteract immunosuppression and increase survival. In the present investigation we have compared nine different inhibitors of PG-synthesis for capacity to enhance phytohemagglutinin responses of blood lymphocytes before and after irradiation for breast cancer. Five of the drugs (aspisol, indomethacin, meclofenamic acid, ketoprofen and diclofenac) enhanced the reactivity to more than 150%. In general, the strongest enhancements were observed in lymphocyte preparations obtained at completion of irradiation when reactivity was most depressed followed by those obtained at one month and before irradiation.

Adult

Immunological changes in primary HIV-1 infection.

Homosexual men with symptomatic primary HIV-1 infection displayed a pronounced lymphopaenia with significantly depressed numbers of CD3+, CD4+ and CD8+ cells and B cells during the first week of illness. Subsequently, the CD8+ cell counts rose in parallel with numbers of CD3+ cells, atypical lymphocytes and activated (CD38+ and HLA-Dr+) cells to attain maximal levels about a month following onset of illness. In contrast CD4+ and B cell numbers remained low for an extended period of time. Early signs of a host response included a transient appearance of interferon-alpha in the blood and raised levels of neopterin and beta 2-microglobulin (beta 2-M). Neither CD4+/CD8+ cell ratio nor beta 2-M resumed completely normal values during a follow-up period of 2 years. These findings shed some light on pathogenetic events during early HIV-1 infection and suggest that the infection, following the acute symptomatic stage, usually enters a stage of chronic active rather than latent infection.

Adult

Changes of the blood lymphocyte population following 32P treatment for polycythemia vera.

Orally administrated Na2 32PO4 mainly accumulates in bone marrow where it emits beta-particles which may damage cells. Previously, we showed that 32P treatment for polycythemia vera (PVC) increased the phytohemagglutinin reactivity and proportions of T cells in the blood. Now we have examined the effects of 32P treatment for PCV on natural killer (NK) and B-lymphocyte subsets which are considered to undergo their maturation in bone marrow. A mean isotope dose of 240 MBq given to 14 patients reduced the peripheral lymphocyte counts to 60% at 6 weeks. B cells and NK cells were reduced to the highest relative extent followed by HNK-1 cells and T cells. Although the proportion of NK cells was reduced to 50% there was no concomitant reduction of NK activity against K562 cells. Pokeweed mitogen-triggered secretion of IgM was significantly reduced, but not that of IgG or IgA. It is suggested that lymphocytes which mature in bone marrow may be affected to the highest extent by 32P treatment in PCV.

Adult

The taxes of sin. Do smokers and drinkers pay their way?

We estimate the lifetime, discounted costs that smokers and drinkers impose on others through collectively financed health insurance, pensions, disability insurance, group life insurance, fires, motor-vehicle accidents, and the criminal justice system. Although nonsmokers subsidize smokers' medical care and group life insurance, smokers subsidize nonsmokers' pensions and nursing home payments. On balance, smokers probably pay their way at the current level of excise taxes on cigarettes; but one may, nonetheless, wish to raise those taxes to reduce the number of adolescent smokers. In contrast, drinkers do not pay their way: current excise taxes on alcohol cover only about half the costs imposed on others.

Alcohol Drinking

Interactions of low density lipoprotein with rat mesangial cells.

Hyperlipidemia may contribute to the pathogenesis of glomerular sclerosis. We therefore studied binding and uptake of low density lipoprotein (LDL) by cultured rat mesangial cells. In addition effects of LDL on PGE2 synthesis and cell proliferation were determined. At 4 degrees C mesangial cells bound [125I] LDL in a time- and concentration-dependent manner with half-maximal binding observed at 5 micrograms/ml of LDL protein. Binding was blocked by excess unlabeled LDL and by heparin. Uptake (binding plus internalization) of LDL at 37 degrees C markedly exceeded binding at 4 degrees C, continued to increase even with longer periods of incubation, and showed no saturability, consistent with uptake of LDL by mesangial cells. Further evidence for LDL uptake by mesangial cells was obtained by use of the fluorescent probe 1,1'-dioactadecyl-3,3,3', 3'-tetramethylindocarbocyanine perchlorate-labeled LDL (Dil-LDL). Incubation of mesangial cells with Dil-LDL at 37 degrees C showed positive fluorescence for all mesangial cells, indicating uptake of the Dil-LDL. LDL had a biphasic effect on mesangial cell proliferation as determined by [3H] thymidine incorporation. LDL at 10 micrograms/ml enhanced [3H] thymidine uptake modestly, but significantly, whereas a progressive and marked inhibition occurred at LDL concentration from 100 to 500 micrograms/ml. While LDL at 10 and 100 micrograms/ml significantly stimulated PGE2 production, inhibition of PGE2 by meclofenamate did not influence the effects of LDL on [3H] thymidine incorporation. We conclude that mesangial cells show specific binding and uptake of LDL and that high concentrations of LDL markedly decrease mesangial cell proliferation. These findings may pertain to the pathogenesis of glomerular lesions in hyperlipidemia of renal disease.

Animals

The external costs of a sedentary life-style.

Using data from the National Health Interview Survey and the RAND Health Insurance Experiment, we estimated the external costs (costs borne by others) of a sedentary life-style. External costs stem from additional payments received by sedentary individuals from collectively financed programs such as health insurance, sick-leave coverage, disability insurance, and group life insurance. Those with sedentary life-styles incur higher medical costs, but their life expectancy at age 20 is 10 months less so they collect less public and private pensions. The pension costs come late in life, as do some of the medical costs, and so the estimate of the external cost is sensitive to the discount rate used. At a 5 percent rate of discount, the lifetime subsidy from others to those with a sedentary life style is $1,900. Our estimate of the subsidy is also sensitive to the assumed effect of exercise on mortality. The subsidy is a rationale for public support of recreational facilities such as parks and swimming pools and employer support of programs to increase exercise.

Adult

Immunosuppression in irradiated breast cancer patients: in vitro effect of cyclooxygenase inhibitors.

We have documented in previous studies that local irradiation therapy for breast cancer caused severe lymphopenia with reduction of both T and non-T lymphocytes. Non-T cells were relatively more depressed but recovered within six months. The recovery of T cells, on the other hand, remained incomplete 10-11 years after irradiation. Several lymphocyte functions were also severely impaired. An association was found between prognosis and postirradiation mitogen reactivity of lymphocytes from these patients. Mortality up to eight years after irradiation was significantly higher in patients with low postirradiation phytohemagglutinin and PPD reactivity. The radiation induced decrease in mitogenic response seemed mainly to be caused by immunosuppressive monocytes, which suggests that the underlying mechanism might be mediated by increased production of prostaglandins by monocytes. For this reason we examined the effect of some cyclooxygenase products on different lymphocyte functions and found that prostaglandins A2, D2, and E2 inhibited phytohemagglutinin response in vitro. Natural killer cell activity was also reduced by prostaglandins D2 and E2. The next step was to examine various inhibitors of cyclooxygenase in respect to their capacity to revert irradiation-induced suppression of in vitro mitogen response in lymphocytes from breast cancer patients. It was demonstrated that Diclofenac Na (Voltaren), Meclofenamic acid, Indomethacin, and lysin-mono-acetylsalicylate (Aspisol) could enhance mitogen responses both before and after radiation therapy. This effect was most pronounced at completion of irradiation. On a molar basis, Diclofenac Na was most effective followed by Indomethacin, Meclofenamic acid, and lysin-monoacetylsalicylate. The clinically beneficial effects of irradiation might be overshadowed by its effects on the immune system. If true, the value of treatment could be improved if radiation-induced suppression of lymphocyte response, which correlates inversely to survival, is reduced. Since such an effect can be achieved in these patients with cyclooxygenase inhibitors in vitro it is possible that it can be achieved also in vivo.

Breast Neoplasms

Influence of adjuvant tamoxifen on blood lymphocytes.

The blood lymphocyte population was studied in 23 breast cancer patients treated with adjuvant tamoxifen for 1.5-2 years, and in an equal number of control patients. The size and cellular composition of the blood lymphocyte population, as assessed by monoclonal antibodies directed against various subsets, did not differ between the two patient groups. However, lymphocytes from the tamoxifen-treated patients exhibited a significantly lower NK activity against K562 cells. In contrast, the proliferative response of lymphocytes to ConA was significantly higher. These results indicate that tamoxifen may modulate the immune system.

Aged

Changes of the blood lymphocyte subpopulations and their functions following 131I treatment for nodular goitre and 32P treatment for polycythemia vera.

The blood lymphocyte population was examined in 34 patients who were treated with 131I for toxic or atoxic nodular goitre. One to three doses of 300-550 MBq of 131I were administered at 1-week intervals. Lymphocyte counts were found to be significantly reduced at both 1 and 6 weeks after treatment. This decrease was accompanied by a changed composition of the lymphocyte subpopulations. The frequency of lymphocytes expressing membrane receptors for C'3 (EAC-rosette forming cells) was significantly reduced at 1 and 6 weeks following 131I administration. At 6 weeks there was a small but statistically significant increase of the frequency of T cells as identified by Leu 1 monoclonal antibodies. This was essentially due to an increased proportion of helper/inducer T cells as identified by Leu 3 monoclonals. 131I treatment also decreased the capacity of lymphocytes to secrete immunoglobulins (Ig) when stimulated with pokeweed mitogen (PWM). The greatest effect was observed for IgM. Secretion of IgG and IgA were less reduced. Mitogenic stimulations of lymphocytes with phytohemagglutinin (PHA) and concanavalin A were not significantly changed. It is concluded that these findings, with the exception of mitogen reactivity, are largely similar to those occurring following external radiation therapy for cancer. It is suggested that blood lymphocytes passing through the continuously irradiated gland are damaged mainly by beta-rays. The effect of 32P treatment on the blood lymphocyte population was examined in 16 patients with polycythemia vera. Before treatment the lymphocyte counts were within the normal range but the expression of certain membrane structures, as identified by monoclonal antibodies against total T cells (Leu 1 and 4), helper/inducer (Leu 3) and suppressor/cytotoxic T cells (Leu 2), were slightly decreased. Moreover, mitogenic responses of the lymphocytes to PHA and PWM-induced Ig secretion were impaired. Following a single oral dose of 32P (150-305 MBq), which normalized the production of erythrocytes and/or platelets, the blood lymphocyte counts were reduced by approximately 40 per cent 12 weeks after treatment. Examination of subsets demonstrated that the proportion of B-cells, as identified by B1 monoclonal antibodies, was decreased by the highest relative extent. On the other hand, lymphocytes expressing the above-mentioned T cell markers were somewhat increased. 32P treatment markedly increased PHA reactivity but it further reduced PWM-induced Ig secretion. The latter observation was in agreement with the finding that serum concentrations of Ig were reduced after treatment.

Aged