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Biomedical subjects

M Berger

Publications and source records attributed to M Berger.

At least 721 records · Page 40Linked to original sources
PubMed1985

Intravenous and standard immune serum globulin preparations interfere with uptake of 125I-C3 onto sensitized erythrocytes and inhibit hemolytic complement activity.

Antibody-sensitized sheep erythrocytes were used as a model to determine the effects of therapeutic immune serum globulin (ISG) preparations on the ability of this particulate activator to fix C3 and initiate hemolysis. Both standard and intravenous forms of ISG inhibit uptake of 125I-C3, presumably by competing for the deposition of "nascent" C3b molecules onto the erythrocytes. Both forms of ISG also inhibit hemolytic activity of whole serum or purified complement components. The inhibition appears to be a specific property of IgG itself, since similar inhibition was not caused by equivalent concentrations of human serum albumin, and was not affected by the buffer in which the ISG was dissolved. Interference with C3 uptake onto antibody-sensitized platelets and/or inhibition of hemolytic complement activity could contribute to the efficacy of high dose intravenous ISG in idiopathic thrombocytopenic purpura.

Complement Activation↗
PubMed1985

The effect of weight loss and inappropriate plasma dexamethasone levels on the DST.

Recent studies from different research groups have raised fundamental questions about the postulated specificity of the dexamethasone suppression test (DST) for endogenous depression. Findings in 116 psychiatric inpatients and 24 semi-starved healthy volunteers underline the importance of weight loss as a factor affecting DST results. A study of 160 DSTs in 93 psychiatric inpatients further revealed a significant negative correlation of plasma cortisol and plasma dexamethasone levels 10 hours after oral administration of 1 mg of dexamethasone. These results suggest a decisive effect of the pharmacokinetics of dexamethasone, at least on the 1-mg DST.

Adolescent↗
PubMed1985

The inhibitory effect of 5-acetoxy-2-(4-acetoxyphenyl)-1-ethyl-3-methylindole (D 16726) on estrogen-dependent mammary tumors.

The antineoplastic activity of the antiestrogen 5-acetoxy-2-(4-acetoxyphenyl)-1-ethyl-3-methylindole (D 16726) was determined in several estrogen-dependent mammary tumor models. The growth of the DMBA-induced rat mammary carcinoma was inhibited by doses ranging from 1 to 12 mg/kg. The maximum decrease of tumor area was 67% (control + 635%). D 16726 was also active against MNU-induced rat mammary tumors and transplanted MXT tumors of the mouse. The growth of estrogen receptor-positive MCF-7 breast cancer cells was inhibited by the hydroxy derivative D 15414 (10(-8)-10(-5) M). Because of the high binding affinity of D 15414 for the estrogen receptor (RBA 6.7-10.0) and the lack of activity against hormone-independent MDA-MB 231 breast cancer cells, a specific mode of action involving the estrogen receptor is likely.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1985

Quantitative assessment of pulmonary hypertension in patients with tricuspid regurgitation using continuous wave Doppler ultrasound.

Doppler ultrasound examination was performed in 69 patients with a variety of cardiopulmonary disorders who were undergoing bedside right heart catheterization. Patients were classified into two groups on the basis of hemodynamic findings. Group I consisted of 20 patients whose pulmonary artery systolic pressure was less than 35 mm Hg and Group II consisted of 49 patients whose pulmonary artery systolic pressure was 35 mm Hg or greater. Tricuspid regurgitation was detected by Doppler ultrasound in 2 of 20 Group I patients and 39 of 49 Group II patients (p less than 0.001). Twenty-six of 27 patients with pulmonary artery systolic pressure greater than 50 mm Hg had Doppler evidence of tricuspid regurgitation. In patients with tricuspid regurgitation, continuous wave Doppler ultrasound was used to measure the velocity of the regurgitant jet, and by applying the Bernoulli equation, the peak pressure gradient between the right ventricle and right atrium was calculated. There was a close correlation between the Doppler gradient and the pulmonary artery systolic pressure measured by cardiac catheterization (r = 0.97, standard error of the estimate = 4.9 mm Hg). Estimating the right atrial pressure clinically and adding it to the Doppler-determined right ventricular to right atrial pressure gradient was not necessary to achieve accurate results. These findings indicate that tricuspid regurgitation can be identified by Doppler ultrasound in a large proportion of patients with pulmonary hypertension, especially when the pulmonary artery pressure exceeds 50 mm Hg. Calculation of the right ventricular to right atrial pressure gradient in these patients provides an accurate noninvasive estimate of pulmonary artery systolic pressure.

Adult↗
PubMed1985

Radiation-induced decomposition of the purine bases within DNA and related model compounds.

This survey focuses on recent developments in the radiation chemistry of purine bases in nucleic acids and related model compounds. Both direct and indirect effects of ionizing radiation are investigated with special emphasis on the structural characterization of the final decomposition products of nucleic acid components. Available assays for monitoring radiation-induced base lesions are critically reviewed.

Adenine↗
PubMed1985

Testosterone and dihydrotestosterone levels in the epididymis, vas deferens and preputial gland of mice during sexual maturation.

The levels of testosterone (T) and dihydrotestosterone (DHT) in the epididymis, vas deferens and preputial gland were assessed in mice from 1 to 90 days. The weight increase of these 3 organs was proportionately greater than that of the whole body until 50 or 60 days, and they attained their adult histological appearance approximately 20 days prior to puberty. Expressed in ng/g, the concentration of androgens (T+DHT) in the epididymis (14.3 to 36.5), vas deferens (6.6 to 24.0) and preputial gland (1.5 to 4.7) were higher than in plasma (0.2 to 3.6 ng/ml). The concentration of either androgen varied little during sexual maturation and was not correlated with circulating levels. The highest concentration of androgen (T+DHT) was observed at birth suggesting that the neonatal period is crucial for development of the accessory sexual organs. In the epididymis and preputial gland T was the predominant androgen during the infantile phase of development, whilst DHT predominated thereafter. In the vas deferens concentrations of T were always equal to or higher than those of DHT. These results suggest that the ability of the accessory sexual organs to accumulate androgens appears to be more important than the circulating concentration of androgens in determining their growth and differentiation.

Androgens↗
PubMed1985

Cytotoxicity of human serum for Leishmania donovani amastigotes: antibody facilitation of alternate complement pathway-mediated killing.

Mechanisms that mediate recovery from leishmanial infection have not been fully characterized but are generally believed to involve interactions between T lymphocytes and macrophages. A major role for serum-mediated effector mechanisms in the protection of humans from reinfection with Leishmania, however, has not been ruled out. In this report, amastigotes of L. donovani were incubated with dilutions of serum from normal subjects and from patients with kala-azar. Normal serum was cytotoxic for parasites at a dilution of greater than or equal to 1:20. Cytotoxicity did not occur in the presence of EDTA, was abolished by heating serum to 56 degrees C for 30 min, and was not diminished by prior adsorption of normal serum with parasites at 0 degree C. Killing proceeded normally in the presence of magnesium-ethylene glycol-bis(beta-aminoethyl ether)-N, N-tetraacetic acid, however, and was fully effected by C2-deficient serum. These studies indicated that killing of amastigotes, unlike that of promastigotes, was mediated via the alternate pathway of serum complement. In further studies, cytotoxicity of normal serum was enhanced three- to fivefold by factors in patient serum. This enhanced cytotoxicity also proceeded via the alternate complement pathway. Factors that enhanced cytotoxicity were characterized as parasite-specific immunoglobulin G: they eluted with immunoglobulin G on column chromatography, were adsorbed by immobilized staphylococcal protein A, and were not removed from the parasite surface by extensive washing. Thus, infection of individuals with L. donovani resulted in the production of a new, qualitatively and quantitatively distinct immune mechanism directed against the amastigote form of the parasite, namely, antibody-directed, alternate complement pathway-mediated cytotoxicity. These results provide a mechanistic framework for a role of humoral factors in human resistance to reinfection with L. donovani.

Animals↗
PubMed1985

The influence of dieting on the menstrual cycle of healthy young women.

Nine normal young women of normal weight, aged 20-29 yr, who had regular menstrual cycles, dieted for 6 weeks (approximately 800-1000 kcal/day) and lost between 6 and 8 kg body wt. Half-hourly blood samples were taken from 1800-0530 h on two occasions before and after 1, 2, 3, 4, 5, and 6 weeks of dieting. In three women with anovulatory cycles the LH secretion pattern was not altered by dieting, but plasma estradiol levels decreased and reached menopausal concentrations during the final 2 weeks of dieting. In two of these three women the menstrual cycles were disrupted and regular cycles occurred only 3 and 6 months after dieting. Six women had regular ovulatory cycles. High progesterone values (greater than 3 ng/ml) were recorded in two cycles before the dieting period. While dieting, three women maintained ovulatory cycles and three women had no periovulatory hormone secretion pattern and/or a pattern characteristic of the luteal phase. No significant alterations of average LH concentrations and LH peak frequency developed. It is concluded that mild dieting does not suppress LH secretion in the manner found in anorexia nervosa or during total fasting. Dieting may interfere with gonadal steroid production, thus causing disturbances of the menstrual cycle. The effect described here may be responsible for the early onset of amenorrhea in patients with beginning anorexia nervosa.

Adult↗
PubMed1985

Outpatient dobutamine infusion using a totally implantable infusion pump for refractory congestive heart failure.

A patient with refractory congestive heart failure was treated, on an outpatient basis, with intermittent dobutamine using a totally implantable infusion pump. Dobutamine was infused for 48 hours every week and resulted in sustained clinical improvement. Symptoms and signs of congestive heart failure remained well controlled until his death from a stroke eight months after implantation of the pump.

Aged↗
PubMed1985

Regulation of gonadotrophin secretion in male mice from birth to adulthood. Response to LRH injection, castration and testosterone replacement therapy.

Plasma LH and FSH concentrations were determined by radioimmunoassay in male mice from birth to adulthood after LRH injection, castration and testosterone replacement therapy. Except at birth for LH, LRH significantly increased circulating levels of both gonadotrophins at all stages studied. It is suggested that a change in the pituitary LH response to LRH occurs around puberty and perhaps represents the time of initiation of pubertal processes. At all stages studied (except the infantile stage for LH) castration resulted in a significant rise in circulating LH and FSH levels. The magnitude of LH response to castration increased with age but not that of FSH. Testosterone replacement therapy, inducing supra-physiological circulating testosterone levels, was ineffective to depress the post-castration rises of LH and FSH levels.

Age Factors↗
PubMed1985

Permanent changes in the functional development of accessory sex organs and in fertility in male mice after neonatal exposure to cyproterone acetate.

Male mice were injected daily with cyproterone acetate for 10 consecutive days during one of the four following periods: 1-10 days, 11-20 days, 21-30 days or 31-40 days. At all stages studied cyproterone acetate caused a significant reduction in the relative weights of epididymis, vas deferens, preputial gland and seminal vesicle in males killed 24 h after the last injection; the androgen content (testosterone + dihydrotestosterone) of the accessory sex organs was also reduced but the differences were not always significant. Cyproterone acetate treatment from 1 to 10 days resulted in a definitive reduction in the relative weights of all accessory sex organs studied and when injected from 11 to 20 days in epididymis and vas deferens. When cyproterone acetate was injected after 20 days of age, the inhibition of sexual organ weights was reversible and at adulthood organs were normally developed. Cyproterone acetate treatment induced a high percentage of infertile males only when injected from 1 to 10 days. Spermatogenesis, androgen levels in plasma and accessory sex organs, and sexual behaviour were not affected in sterile males. These results suggest that the functional development of accessory sex organs can be permanently affected by short-term neonatal exposure to endogenous androgens.

Age Factors↗
PubMed1985

Stem cell studies of human malignant brain tumors. Part 2: Proliferation kinetics of brain-tumor cells in vitro in early-passage cultures.

The proliferation kinetics were studied in early-passage cultures of cells from 13 human malignant brain tumors and two specimens of normal brain under conditions similar to those used in clonogenic cell-survival studies. Autoradiography was performed in all but four cases to estimate the fraction of cells actively replicating deoxyribonucleic acid (DNA), the approximate cell cycle time, and the effect of low-dose tritiated thymidine on cell proliferation. The mean tumor cell doubling time (TD) was 53 hours for five glioblastomas, 46 hours for two ependymomas, and 83 hours for two medulloblastomas. A gliosarcoma grew fastest (TD = 22 hours) in culture and a pilocytic astrocytoma grew slowest (TD = 144 hours). The approximate cell cycle time ranged from 1 to 2.5 days for all tumors tested. This suggests that chemotherapeutic agents that predominantly kill proliferating cells should be administered in vitro for at least 2 to 2.5 days to achieve maximum cell kill. The approximate growth fraction ranged from 0.65 to 0.96 for all tumors except for the two medulloblastomas and the pilocytic astrocytoma, which had growth fractions of 0.34 and 0.35, respectively. Most laboratories investigating the chemosensitivity of primary or early-passage human tumor cells require that 40% to 70% of cells be killed to consider a drug active in vitro. The results of this study suggest that the cell-cycle-specific agents cannot achieve a high enough cell kill to be considered active for some tumors that grow slowly in culture. An estimate of the in vitro growth rate is necessary to reliably interpret cell-survival results with such agents. Tritiated thymidine appeared to slow cell proliferation in some of the cultures, presumably as a result of radiation-induced DNA damage caused by tritium that had been incorporated into DNA. The degree to which cell growth ws slowed in individual tumors correlated with the patient's clinical response to radiation therapy and postoperative survival time.

Brain Neoplasms↗
PubMed1985

Chemical structure of carbamoylating groups and their relationship to bone marrow toxicity and antiglioma activity of bifunctionally alkylating and carbamoylating nitrosoureas.

Although the antitumor effects of chloroethylnitrosoureas have been shown to be due primarily to DNA-DNA cross-linking by the alkylating moieties of these agents, the basis of the often accompanying bone marrow toxicity has been more controversial. We report on the relative bone marrow toxicity of four model nitrosoureas with different alkylating and carbamoylating activities: 1,3-bis(2-chloroethyl)-1-nitrosourea; 1,3-bis(trans-4-hydroxycyclohexyl)-1-nitrosourea; chlorozotozin, (2-[3-(2-chloroethyl)-3 -nitrosoureido]-2-deoxy-D-glucopyranose); and -3-(beta-D-glucopyranosyl)-1-nitrosourea. Inhibitions of DNA, RNA, and protein synthesis in murine bone marrow cells and of colony growth of myeloid precursor cells (granulocyte-macrophage colony-forming units) were used as in vitro end points of myelotoxicity. Further, we determined the antiglioma activity of the four nitrosoureas on two human gliomas in a clonogenic tumor cell assay and studied the effect of the non-nitrosourea carbamoylators potassium cyanate, chloroethyl isocyanate, cyclohexyl isocyanate, ethyl isocyanate, and ethyl isothiocyanate on granulocyte-macrophage colony-forming units. The results show that, at equivalent drug exposures, clonogenic glioma cell kill was significant and comparative for 1,3-bis(2-chloroethyl)-1-nitrosourea, 1-(2-chloroethyl)-3-(beta-D-glucopyranosyl)-1-nitrosourea, and chlorozotocin; 1,3-bis(trans-4-hydroxycyclohexyl)-1-nitrosourea showed little activity. In contrast, granulocyte-macrophage colony-forming unit toxicity was low with chlorozotocin and 1-(2-chloroethyl)-3-(beta-D-glucopyranosyl)-1-nitrosourea and very high with 1,3-bis(2-chloroethyl)-1-nitrosourea and 1,3-bis(trans-4-hydroxycyclohexyl)-1-nitrosourea. Of the isocyanates, bone marrow toxicity was highest with chloroethyl isocyanate and cyclohexyl isocyanate, intermediate with ethyl isocyanate, and lowest with KOCN and ethyl isothiocyanate. Our results indicate that (a) bifunctional alkylation is essential for antiglioma activity of nitrosoureas and (b) myelosuppression is at least partly linked with carbamoylation but that structural entities in the carbamoylating isocyanate rather than a quantitative degree of carbamoylation determine the degree of potential myelotoxicity.

Alkylating Agents↗
PubMed1985

Mechanism of priming of human neutrophils by a soluble lymphoblastoid cell factor.

Treatment of human neutrophils (PMN) with a cytokine-like factor in the supernatants of human lymphoblastoid cells (Raji) increased the random mobility and enhanced the migration of treated cells in response to other chemoattractants nearly 21/2-fold, although the supernatant itself was not a chemoattractant. Supernatant treatment also increased the adherence of bacteria threefold and the bacterial killing fourfold compared with PMN treated with control media. In examining the metabolic basis for the enhanced bactericidal ability, we observed a significant increase in spontaneous hexose monophosphate shunt activity of Raji cell supernatant (RS)-treated neutrophils even in the absence of additional stimuli. RS-treated PMN also had significantly enhanced production of superoxide anion and chemiluminescence response upon subsequent stimulation with a variety of soluble and particulate stimuli. Unlike other agents that prime neutrophil activation, however, the factor(s) in RS did not cause degranulation. It also differed in its ability to progressively enhance PMN functions with a longer period of preincubation (up to 3 hr). These data suggest that the RS factor(s) primes neutrophils by a unique mechanism. The neutrophil-enhancing activities of RS, which are the opposite of those activities described for leukocyte inhibitory factor, eluted off a Sephacryl S-200 column at approximately 30,000 m.w. This factor expands the relationship between neutrophils and lymphocytes, and may be a useful agent to provide valuable insights into the mechanism of respiratory burst activation and regulation.

B-Lymphocytes↗