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Biomedical subjects

M J Becker

Publications and source records attributed to M J Becker.

At least 19 recordsLinked to original sources
PubMed1992

Effector cells of low-dose IL-2 immunotherapy in tumor bearing mice: tumor cell killing by CD8+ cytotoxic T lymphocytes and macrophages.

The presence and cytotoxicity of tumor infiltrating cells is described in mice during effective immunotherapy with interleukin 2 (IL-2). DBA/2 mice were inoculated i.p. with 2 x 10(4) tumor cells on day 0 and treated with daily i.p. injections with 20,000 units IL-2 on days 10-14. Mice bearing a large syngeneic i.p. tumor burden (SL2 lymphoma, P815 mastocytoma, L5178Y lymphoma, or L1210 lymphoma) could be cured by i.p. immunotherapy with these low doses of IL-2. In the peritoneal cavity of these mice an infiltrate of mononuclear cells was present. Similar numbers of lymphocytes (10(6)-10(7)) and macrophages (+/- 10(7)) were present in control tumor bearing mice and IL-2 treated tumor bearing mice. The ratio of CD4+/CD8+ T lymphocytes in the peritoneal cavity of mice rejecting the SL2 tumor was smaller than 0.5, whereas this ratio is about 2 in naive mice. In the spleens of IL-2 treated tumor bearing mice only a minor decrease of CD4+/CD8+ ratio was observed from 2.1-2.4 to 0.9-1.9. T cells isolated from the peritoneal cavity of mice inoculated with SL2 tumor cells and treated with IL-2, were highly cytotoxic to SL2 cells: at E:T ratio 2:1 the cytotoxicity index was 37 +/- 3. This cytotoxicity was specific and mediated by CD8+ T lymphocytes. Macrophages that were present in the peritoneal cavity of mice treated with IL-2 were also highly cytotoxic. The C.I. of these cells was 63-76% at E:T ratio 1:1. Cytotoxic macrophages were also present in untreated tumor bearing mice. The i.p. injections of IL-2 (20,000 units/day) caused a four-fold increase in the local NK-activity in the peritoneal cavity in naive mice. These IL-2 injections did not generate LAK-activity in vivo. Specificity of the in vivo tumor rejection was tested by injection SL 2 i.p. on day 0 and P815 i.p. on day 10, or vice versa, followed by IL-2 treatment. Only the tumor cells that were injected on day 0 were rejected. These in vivo experiments point to specific tumor rejection. In conclusion, both cytotoxic macrophages and CTL's are present in a sufficient number and with sufficient cytotoxicity to explain the killing of tumor cells in the peritoneal cavity. The CTL-activity seems of decisive importance for tumor rejection as this is induced by IL-2.

Animals↗
PubMed1985

Fiber optic probe cytometer.

An optical fiber probe is used to both excite and collect fluorescence from a suspension of cells. The configuration of the probe is such that one or a few cells are sensed at a time, with a convenient cell concentration. With fluorescently labeled antibodies to cellular antigens, the fiber optic cytometer is able to identify the presence of a specific set of cells with high sensitivity.

ABO Blood-Group System↗
PubMed1984

Electrodiagnostic tests in the detection of malignant hyperthermia.

Malignant hyperthermia (MH) can be a catastrophic and sometimes fatal reaction in certain susceptible individuals who are exposed to skeletal muscle relaxants such as succinylcholine and/or certain inhalation anesthetics such as halothane. In an attempt to develop a safe, simple in vivo test to identify the at-risk patients, repetitive nerve stimulation (RNS) and electromyographic (EMG) studies were performed on 9 patients with MH, 15 patients suspected of having MH, and 9 control subjects. Serial recordings were made following injections of caffeine sodium benzoate, succinylcholine, and halothane at the test site. Measurements were done on the amplitude of the evoked compound motor action potentials (CMAP), on RNS, and on the number of negative peaks of motor unit potentials (MUP) on maximum EMG recruitment. The results showed the effects of the drugs on amplitudes of the CMAPs to be significant (P less than 0.001) in all three groups, but no significant differences were found among the groups (P = 0.93). The negative peaks of MUP on EMG recording showed a significant difference upon introducing succinylcholine (P less than 0.001), and significant interaction effects of the treatment by the patient group. Preliminary comparisons of in vivo tests with in vitro contracture tests in nine patients showed good correlation.

Adolescent↗
PubMed1981

Monocyte-mediated regulation of cellular immunity in humans: loss of suppressor activity with ageing.

The effect of ageing on cellular immunity in humans was investigated. Human T cell cytotoxicity (CMC) measured by an in vitro xenogeneic assay was found previously to be depressed in individuals greater than 60 years old (group 2) compared to individuals less than 50 years old (group 1). Removal of plastic-adherent cells prior to sensitization in the xenogeneic CMC assay of human peripheral blood mononuclear cells (HPBM) resulted in a significantly higher rise (P less than 0.001, Wilcoxon rank test) in CMC activity in group 1 compared to group 2. Replacement of plastic-adherent cells (greater than 35% monocytes) to HPBM depleted of monocytes returned the CMC activity to the level observed with unseparated HPBM. Separation of HPBM on Percoll density gradients into monocyte-enriched (less than 75%) and monocyte-depleted (less than 3%) fractions indicated that monocytes were responsible for suppressing CMC in group 1. These results are consistent with the hypothesis that monocyte suppressor function for CMC response declines in ageing humans. When indomethacin (1 microgram/ml) was added to HPBM the Con A- and PHA-induced DNA synthetic response rose in groups 1 and 2. Indomethacin induced a significantly larger (P less than 0.01) rise in suboptimal PHA mitogenesis in group 1 compared to group 2. Individuals whose CMC response rose following adherent cell depletion were examined for the effect of indomethacin on the CMC response of their HPBM. In nine of 13 cases, addition of indomethacin also resulted in increased CMC activity.

Adult↗
PubMed1979

Age-related changes in antibody-dependent cell-mediated cytotoxicity in mouse spleen.

The age-related variation in antibody-dependent cell-mediated cytotoxicity (ADCC) in spleen was examined in four different mouse strains (DBA/2, Balb/c, NZB and NZB/NZW). The ADCC effector activity against antibody-coated chicken red blood cells in untreated spleen from all four strains was roughly comparable. An initial rise in activity with increasing age until two to three months was followed by a sharp decline in effector activity. Treatment of the spleen cells with poly-l-lysine-coated carbonyl iron to remove phagocytes resulted in a decrease in ADCC activity in NZB, NZB/NZW and DBA/2 strains at all ages examined. The same general pattern of age-dependent decline was still seen in these depleted spleens. However, the same treatment essentially abolished ADCC in Balb/c spleen at all ages studied.

Age Factors↗
PubMed1977

Premature contraction of the ductus arteriosus: a cause of foetal death.

Necropsy findings are presented of two cases of foetal heart failure secondary to premature, in-utero contraction should lead to a redirection of the right heart output either through the pulmonary vascular bed or to the systemic circulation via the foramen ovale. The muscular pulmonary arteries, however, were not dilated, indicating that no excessive pulmonary flow had occurred. The increased volume load on the right heart may have rendered the foramen ovale restrictive, with right-sided heart failures as a consequence. Premature closure of the ductus arteriosus should be considered a cause of foetal or early neonatal death.

Constriction, Pathologic↗
PubMed1977

Immune complexes in hepatitis B antigen-associated periarteritis nodosa. Detection by antibody-dependent cell-mediated cytotoxicity and the Raji cell assay.

A subpopulation of peripheral blood lymphocytes with the ability to lyse target cells coated with specific antibody (antibody-dependent cell-mediated cytotoxicity, ADCC) was serially studied in a patient with hepatitis B antigen-associated periarteritis nodosa. The effector lymphocytes possess FC and complement receptors but do not require complement for functional activity. We found that the patient's ADCC was decreased during periods of disease activity and was almost normal during remission. The patient's serum could block ADCC in normal lymphocytes, and the blocking ability correlated with the concentration of immune complexes as determined by the Raji cell assay (a radioimmunoassay using complement receptors on human cultured lymphoblastoid cells). The concentration of immune complexes and the ADCC blocking ability of ther serum both correlated with disease activity. Serum from five other patients with active vasculitis was found to contain significant amounts of immune complexes and was able to block normal ADCC. It appears that the ADCC assay can be used to detect the presence of circulating immune complexes and to monitor disease activity in periarteritis nodosa.

Adult↗
PubMed1976

Fat distribution in the adrenal cortex as an indication of the mode of intrauterine death.

The presence of fat in the fetal zone of the adrenal cortex in the stillborn macerated fetus is indicative of the mode of intrauterine death. Three basic patterns are recognized. In the type I pattern there is only a scant amount of fat, close to the medullary zone. In the type II pattern fat is more widespread and is present in many more cells of the fetal zone. The type III pattern reflects a massive fatty change of almost all cells throughout the fetal cortical zone. Correlation of the three fat patterns with the pathology of the placenta and clinical data relevant to the etiology of intrauterine death has led to the following conclusions. The type I fat pattern is indicative of an acute mode of death, the type II pattern is indicative of a more prolonged period of intrauterine deterioration prior to death, whereas the type III pattern is indicative of a chronic mode of death. Determination of the fat patterns in the fetal zone of the adrenal cortex can be helpful when the clinician is confronted with the problem of fetal death, especially when maceration may hamper more detailed pathologic studies.

Adrenal Cortex↗
PubMed1976

Antibody-dependent cell-mediated cytotoxicity in selected autoimmune diseases.

Antibody-dependent cell-mediated cytotoxicity mediated by peripheral blood lymphocytes was studied in patients with systemic lupus erythematosus, polyarteritis nodosa. Sjogren's syndrome, and rheumatoid arthritis. The target cells were chicken erythrocytes coated with rabbit anti-chicken erythrocyte antibody. Antibody-dependent cell-mediated cytotoxic activity was normal in Sjogren's syndrome and rheumatoid arthritis but significantly decreased (P is less than 0.001) in active systemic lupus erythematosus and in two patients with polyarteritis nodosa. A partial regeneration of antibody-dependent cell-mediated cytotoxic activity was obtained by treatment with pronase and DNase followed by overnight incubation. Sera from patients with systemic lupus erythematosus inhibited antibody-dependent cell-mediated cytotoxic activity of normal lymphocytes. The inhibitory activity was studied by specific immunoadsorption and sucrose density geadient ultracentrifugation. Removal of IgG but not IgM greatly reduced inhibition. Inhibitory factors were present in 7S and heavier fractions containing IgG. Five systemic lupus erythematosus patients were studied serially to determine if improvement in clinical status could be correlated with a decrease in serum inhibitory factors as studied by inhibition of normal antibody-dependent cell-mediated cytotoxicity. Indeed, a greater serum inhibitory capacity was found in each patient during periods of greater disease activity.

Adult↗
PubMed1976

In vitro effect of thymosin on T-lymphocyte rosette formation in rheumatic diseases.

The in vitro effect of calf thymosin fraction 5 on T-rosette forming cells (E-RFC) was studied in Sjögren's syndrome (SS), rheumatoid arthritis (RA), and systemic lupus erythematosus (SLE). The baseline percent E-RFC in sixteen normal controls was67-2 +/- 6-9. E-RFC was significantly decreased in SLE (42-6 +/- 17-0, P less than 0-0001) and SS (51-8 +/- 16-9, P less than 0-002) but not in RA (59-7 +/- 14-1). Ten of twenty-five SS patients and two of eleven RA patients had less than 50% E-RFC, and all showed a significant increase after incubation with thymosin (+ 16-5 +/- 6-5%, P less than 0-0001, and + 11 +/- 4-9%, P less than 0-001, respectively). Eleven of sixteen SLE patients had less than 50% E-RFC. Their response to thymosin was less dramatic but still statistically significant (+ 5-3 +/- 6-0%, P = 0-03). There was no response to thymosin in control subjects or in patients with baseline E-RFC greater than 50%. No increase in E-RFC was seen after incubation with calf spleen fraction 5 or known stimulators of cyclic-AMP. Sera from four active SLE patients, as well as the supernatant obtained from overnight culture of the lymphocytes from one SLE patients, were able to block T-rosette formation by normal lymphocytes, even after exposure to thymosin. Two 'blocking' sera were fractionated by sucrose density gradient ultracentrifucation. In one, the blocking capacity was found to reside in the 19S region containing IgM. In the second, the blocking capacity was in the 7S region containing IgG. Four 'blocking' lupus sera were depleted of IgG or IgM by immunoabsorption with goat anti-human IgG or goat anti-human IgM sepharose 4B. The blocking ability in three sera was partially decreased by depletion of either IgG or IgM, and in a fourth, only by removing IgG. The percent of lymphocytes staining with fluorescein labelled goat anti-human immunoglobulin antisera was increased in SLE patients (35-9 +/- 20-2 vs 21-7 +/- 5-9 in controls, P = 0-02). After overnight culture, the percent of staining cells decreased to normal values. These results suggest that thymosin can stimulate the differentiation of T-lymphocytes in patients with SS, SLE, and RA when the baseline E-RFC is decreased. Furthermore, the decreased percent E-RFC in SLE is probably due to cell-bound anti-lymphocyte antibodies that block sheep erythrocyte receptors on the T-cell and, possibly, thymosin receptors on undifferentiated lymphocytes.

Adolescent↗
PubMed1976

Serum cortisol (hydrocortisone) values in normal dogs as determined by radioimmunoassay.

A radioimmunoassay method was utilized to determine serum cortisol (hydrocortisone) concentrations in normal dogs. The mean value was 2.32 mug/dl (minimum, 0.94; maximum, 3.70; with a coefficient of variation of 29.7%). Samples had been collected in the morning of the diurnal cycle. The cortisol antibody used was highly specific for cortisol and showed little cross reaction with other common physiologic corticosteroids, when they were assayed, using the radioimmunoassay procedure described.

Animals↗
PubMed1975

p-Azobenzenearsonate-L-tyrosine-mediated helper function in immune responses of guinea pigs and rats.

A small bifunctional antigen (4-hydroxy-5-iodo-3-nitrophenyl)acetyl-epsilon-aminocaproyl-L-tyrosine-azobenzene-p-arsonate [NIP-cap-TYR(ABA)] was found to induce fair humoral antibody formation against NIP-cap but very little anti-ABA-TYR. This was observed in rats and guinea pigs. Prior immunization with ABA-TYR, either as such or coupled to dodecanoylated bovine serum albumin (lipid-BSA), primed rats for an enhanced anti-NIP response to NIP-cap-TYR(ABA). An attempt to encourage rats to produce anti-ABA-TYR in response to the bifunctional antigen by priming them with NIP-cap-lipid-BSA failed. Priming with ABA-TYR was dose-dependent. An injection of 1.5-15 nanomoles per rat primed for an increased production of anti-NIP while 150 nanomoles did not. Adult thymectomized x-irradiated rats had a poor anti-NIP response to the bifunctional antigen if they were reconstituted with T-enriched lymphoid cells from control mice, but a good response if reconstituted with similar cells from ABA-TYR-primed syngeneic rats.

Animals↗
PubMed1975

Antibodies binding polyriboadenylic acid in systemic lupus erythematosus. Immunochemical characterization and isolation by affinity chromatography.

Antibodies specific for polyriboadenylic acid (poly rA) are present in sera from patients with systemic lupus erythematosus and from NZB/NZW F1 mice. The specificity of these antibodies was established by inhibition of [3H]poly rA binding and by affinity chromatography. Poly rA binding was associated with the 19S and 7S regions when serum was fractionated by sucrose density gradient untracentrifugation. Young NZB/NZW F1 mice (1-5 months) had only 19S anti-poly rA, whereas old NZB/NZW F1 mice (2 years) had activity in both 19S and 7S regions, suggesting a possible age-dependent switching mechanism in the spontaneous development of antibodies to nucleic acids. The gamma-globulin fraction from an SLE patient was subjected to affinity chromatography on a column of poly rA covalently linked to Sepharose. An enriched population of IgG antibodies binding only poly rA, but not native or denatured DNA, was isolated in this manner. This procedure may have broad biological applicability for the preparation of isolated immunospecific anti-nucleic acid antibodies.

Age Factors↗