Search PubMed⌕ Search

Biomedical subjects

M Berger

Publications and source records attributed to M Berger.

At least 775 records · Page 43Linked to original sources

Sexual maturation in male mice treated with cyproterone acetate from birth to puberty.

Cyproterone acetate was administered every 2 days from 1 to 39 days of age to male mice which were killed 24 h or 20 days after the last injection. Cyproterone acetate caused a significant reduction in the relative weights of the epididymis, vas deferens, seminal vesicle and preputial gland, which was still evident at 60 days after birth. Testicular and epididymal androgens (testosterone and dihydrotestosterone) and circulating LH and FSH concentrations were equal to or higher than those of controls at 60 days. Cyproterone acetate did not inhibit spermatogenesis but all males were infertile. The results suggest that the peripheral effects of testosterone are necessary, during early stages of sexual maturation, in order to obtain subsequent full development of the accessory sex organs.

Aging↗

Elevated pancreatic glucagon in obesity.

Because of conflicting reports on plasma levels of total immunoreactive glucagon (IRG) in obesity, we investigated, by gel filtration, the individual IRG fractions in grossly obese patients (N = 16; BMI 40 +/- 2) as compared with normal weight subjects (N = 18). Mean total IRG was 142 +/- 12 pg/ml in normal subjects and 190 +/- 15 pg/ml (P less than 0.02) in obese subjects. IRG3500 was 16 +/- 2 pg/ml in normal subjects and 34 +/- 5 pg/ml (P less than 0.005) in the obese subjects. Obese patients with normal glucose tolerance demonstrated 30 +/- 5 pg/ml IRG3500 (N = 11; P less than 0.01) as compared with those who were obese with impaired glucose tolerance (42 +/- 12 pg/ml, N = 5; P less than 0.0025), although the total IRG of the latter group (173 +/- 31 pg/ml) was not different from that of normal subjects. IRG90000 was of comparable magnitude in the entire groups of obese and normal subjects. A wide variability of big plasma glucagon levels was found in all three groups, mean levels not being significantly different. These data suggest that plasma IRG3500 levels are elevated in grossly obese patients, particularly in those patients with impaired glucose tolerance, a finding that may be masked by mere measurements of total plasma IRG.

Adult↗

Effects of accelerating growth on the onset of puberty in male mice.

Sexual maturation was evaluated in male mice subjected to prenatal and preweaning overnutrition induced by reduction of litter size in embryonic and post-natal life. From birth to adulthood body weight was higher in overfed males than in controls. Plasma and testicular testosterone levels followed a similar pattern in normally fed and overfed males. Adult gonadotrophin levels were attained at 30 (FSH) and 40 (LH) days in controls and as soon as 20 days in overfed males. First fertile matings occurred at the same age in both groups. Overnourished males attained puberty when weighing considerably more than controls (34.7 +/- 0.4 vs. 29.4 +/- 0.3 g). The 30-day-old overfed males, which have attained the critical pubertal body weight of controls, were sexually immature. The data showed that in male mice puberty does not seem to be triggered by the attainment of a critical body weight.

Animals↗

The interference of T cell activation by calcium channel blocking agents.

Calcium has been identified as having an important role as a transmembrane messenger in the activation signal for lymphocytes. To additionally examine this model, we evaluated the effect of calcium channel blocking drugs (verapamil, nifedipine, and diltiazem) on lymphocyte activation. In these studies we found that the drugs inhibit, in a dose-dependent fashion, the proliferation of T cells and the appearance of certain activation antigens after mitogen stimulation. This appears to result from the marked decrease in mitogen-induced 45calcium (45Ca+2) influx secondary to the addition of these agents. In addition, T cell proliferation resulting from IL 2 binding to its receptor is also suppressed by the calcium channel blocking drugs. These data suggest that the passive calcium channel plays a pivotal role in both the initial activation of T cells after ligand-receptor interaction and the ongoing signal for proliferation provided by IL 2 binding to its receptor.

Adult↗

A quantitative analysis of C3 binding to O-antigen capsule, lipopolysaccharide, and outer membrane protein of E. coli 0111B4.

The binding of serum C3 to the O-antigen capsule (OAg Cap), lipopolysaccharide (LPS), and outer membrane proteins (OMP) of Escherichia coli 0111B4 was examined. Bacteria were intrinsically labeled with [3H] or [14C]galactose (*gal) in the OAg Cap and LPS moieties or with [14C]leucine (*leu) to label proteins. Organisms were then incubated in serum containing differentially labeled C3, the above fractions were separated, and the proportion of each binding to a column containing anti-C3 was measured. The OAg Cap fraction bound 72 to 82% of the C3, which bound to E. coli 0111B4 during incubation in absorbed 10% pooled normal human serum (10% PNHS) or absorbed 40% C8-deficient serum (C8D). This distribution did not change when the organism was presensitized with immune IgG before serum incubation. A total of 2.93% +/- 0.48 of OAg Cap and 0.52% +/- 0.16 of LPS *gal bound specifically to Sepharose-containing antibodies to C3 (A:C3-Seph) after incubation in 10% PNHS; these values increased to 10.1% +/- 4.5 and 1.8% +/- 0.3, respectively, when C3 deposition was increased fourfold by incubation in 40% C8D. When encapsulated E. coli 0111B4 was incubated in 10% PNHS containing biotinylated C3, specific attachment of OAg Cap *gal to avidin-Sepharose was demonstrated in 1% sodium dodecyl sulfate (SDS), and complete release of bound *gal but not C3 occurred with 1 M NH2OH. When a mutant of E. coli 0111B4 lacking OAg Cap was incubated in 40% C8D, the outer membrane (OM) bound 85% of C3. Five percent of OM *gal from the unencapsulated organism bound to A:C3-Seph in 0.05% SDS, indicating that the fraction of LPS molecules with bound C3 increased threefold in the absence of OAg Cap. OAg Cap does not contain protein, and no net specific binding of *leu from OAg Cap fractions to A:C3 was detectable; 2.4 to 3.6% of OM *leu bound to A:C3-Seph. Immunoprecipitation of 82.9% of OAg Cap *gal with antisera that were directed to E. coli 0111B4 was associated with co-precipitation of 69.5% of C3 in the capsular fraction. Therefore, the majority of C3 bound to E. coli 0111B4 was covalently attached to OAg Cap and LPS. As corroboration of experiments with whole bacteria, purified OAg Cap and purified LPS consumed C3 when incubated in serum in the fluid phase. These results are the first to evaluate the acceptor site for C3 deposition on a Gram-negative organism incubated in serum, and show that LPS, OAg Cap, and OMP are all major acceptor sites for C3 in nonimmune serum.

Animals↗

Modulation of human B cell immunoglobulin secretion by the C3b component of complement.

The human C3b component of complement was found to inhibit the differentiation of human B lymphocytes into immunoglobulin-secreting cells in vitro. Pokeweed mitogen (PWM)-induced plaque-forming cell (PFC) responses were inhibited by C3-coated zymosan particles and by purified human C3b. C3b inhibited the PWM-driven responses in a dose-dependent fashion, and it was necessary for C3b to be present in the early phases of the cultures. C3b acted directly on B cells rather than on helper T cells because it inhibited the PFC responses of MNC depleted of T cells and subsequently stimulated with a T cell-independent Epstein Barr virus mitogen. Furthermore, C3b failed to stimulate the generation of suppressor lymphocytes and/or monocytes that might have been responsible for the inhibition of B cell responses. Our results indicate that C3b or its fragments exert negative modulatory effects on human B lymphocyte responses.

Antibodies↗

Lymphoblastoid cell supernatants increase expression of C3b receptors on human polymorphonuclear leucocytes: direct binding studies with 125I-C3b.

Human PMN incubated in culture supernatants of the Raji long-term human lymphoblastoid cell line showed increased rosette formation with sheep erythrocytes coated with C3b (EIgM C4b3b) but no change in rosette formation with IgG-coated erythrocytes. This suggested a specific increase in cell surface C3b receptors, which was further investigated using 125I-C3b for direct binding studies. The results confirmed that specific binding of 125I-C3b to PMN incubated in culture supernatants increased up to three- to four-fold over binding to PMN incubated in control media alone. Scatchard analysis revealed that the apparent Ka for supernatant-treated cells, 3.36 +/- 0.89 X 10(7) L/M did not differ from the Ka for cells incubated in control media, 3.76 +/- 0.75 X 10(7) L/M, suggesting an increase in a single class of C3b receptors. Kinetic studies revealed that the active factor was present within 24 hr of culture of the Raji cells, and that neutrophils incubated in culture supernatants increased their C3b receptors continuously for up to 4 hr, the longest interval tested. The effect of the culture supernatant was lost with dilution beyond eight- to 10-fold. The results suggest that culture supernatants of this long-term lymphoblastoid cell line contain soluble factors that induce increased expression of C3b receptors on PMN and may thus serve as a model for study of important physiologic effects of lymphocyte products on PMN in vivo.

Cell Line↗

The effect of phenoxybenzamine on postoperative urinary complications during extradural morphine analgesia.

One hundred and fifty patients, post-Caesarean section, were investigated to evaluate the effect of epidural morphine analgesia and that of phenoxybenzamine on the frequency and extent of urinary complications. Forty patients (group A) underwent Caesarian section under general anaesthesia, while 110 patients received epidural anaesthesia. Of the latter patients, 40 received postoperative mild analgesics (group B) whilst in another 40, postoperative continuous epidural morphine was administered (group C). Thirty patients who received postoperative epidural morphine, also received oral phenoxybenzamine 10 mg, 24 and 1 hr prior to, and 8 and 16 hr following surgery (group D). The volume of urine of the first two postoperative voidings, the time delay to first micturition, difficulty in micturition and urinary retention necessitating bladder catheterization were studied. The mean volumes of the first two postoperative voidings were markedly reduced in group C (219 and 218 ml, respectively) as compared with group A (383 and 453 ml) and with group B (319 and 414 ml, respectively). In group D, these mean volumes were significantly larger at 478 ml (p less than 0.01) and 417 ml (p less than 0.01) as compared with those of group C. The mean time to the first postoperative voiding was 582 min in group C, which was significantly longer than that in group A (339 min) or in group B (448 min). In the patients treated with phenoxybenzamine, the time to the first postoperative voiding was significantly less at 322 min (p less than 0.01). The need for bladder catheterization was also increased in group B compared with group A, while in group C this increase was marked compared with both groups A and B. It was significantly less frequent in those receiving phenoxybenzamine. Phenoxybenzamine is recommended in the prevention of postoperative urinary complications associated with epidural anaesthesia and epidural morphine analgesia.

Adult↗

Killing of Leishmania tropica amastigotes by factors in normal human serum.

Amastigotes of Leishmania tropica and L. donovani were incubated with fresh or heat-inactivated normal human serum. Viability was estimated by amastigote conversion to promastigote forms and by the ability of serum-treated amastigotes to infect human monocytes. L. tropica, a parasite that causes local skin infection, was killed by fresh but not by heat-inactivated serum. The serum cytotoxic effect on L. tropica was inhibited by EDTA but not by Mg-EGTA. C2-deficient serum killed normally; C6-deficient serum was ineffective. These data indicate that L. tropica is killed by the complement membrane attack complex, in a sequence of reactions initiated by components of the alternate pathway. In contrast, L. donovani, a parasite that causes systemic visceral leishmaniasis, was 10-fold less susceptible to the cytotoxic effects of normal serum. Thus, a profound difference exists in the susceptibility of amastigotes of two species of Leishmania to a defense mechanism present in human serum. Serum complement factors may play an important role in limiting L. tropica to the skin. The resistance of L. donovani to such factors may be the primary reason for its ability to escape from the site of inoculation and cause catastrophic, disseminated disease.

Animals↗

[Tamponade caused by subacute pericarditis in Basedow's disease].

No case of cardiac tamponade due to subacute pericarditis in the course of Grave's disease has yet been reported. From the 2 cases presented here it would appear that the association is mere coincidence, the clinical manifestations of the pericarditis being probably aggravated by the hyperthyroidism which facilitates the development of oedema and serous effusions.

Adult↗

Autoradiographic visualization of [3H]kainic acid receptor subtypes in the rat hippocampus.

Unfixed, slide-mounted tissue sections from the rat forebrain have been incubated in the presence of 20 and 100 nM [3H]kainic acid ([3H]KA). For the last 2 min of incubation, 10 micrometers unlabelled KA was added to displace [3H]KA from binding sites with high on-off rate. Washed and dried slices were exposed on [3H]Ultrofilm for 178 days. Our results confirm the high density of KA receptors in the terminal field of the hippocampal mossy fibre system which is shown to be due to receptors with slow dissociation rate. Furthermore, the concentration dependency of the specific labelling, as quantified by microdensitometry, allows some suggestions concerning the local binding affinities involved.

Animals↗

Noncarcinogenic chemotherapy with a combination of vincristine, methotrexate and 5-fluorouracil (VMF) in rats.

The CMF regimen, which is clinically used in adjuvant therapy of breast cancer, is known to be carcinogenic in rats (Habs and Schmähl, 1981). To examine alternative regimens, a long-term carcinogenicity study was performed, using the VMF regimen as follows: V (i.v.), M (i.p.) and F (p.o.) at 0.8, 20 and 300 mg/m2, respectively. These doses and a half-dose regimen (0.5 VMF) were administered every 6 weeks to 80 rats (40 males, 40 females) in each of three groups. Group I served as an untreated control. Groups II, III and IV received 6 X VMF, 18 X 0.5 VMF and 18 X VMF, respectively. Unlike treatment with comparable doses of CMF, the present therapy did not result in an increased tumor rate or a change in tumor type over controls. The chemotherapeutic efficacy of VMF was compared with that of CMF by administering the following doses (mg/m2 i.p.) to groups of 20 rats bearing methylnitrosourea-induced primary mammary carcinomas: group 1:C (420), 2:V (2.1), 3:M (35) and F (350), 4:C (210), M (21) and F (280), 5:V (1.05), M (21) and F (280), 6: as in 4 except that C was given 24 h prior to M and F, 7: as in 5 except that V was given 24 h prior to M and F, 8: ovariectomy on day 1, 9: control group. Animals bearing a tumor volume of greater than or equal to 0.8 cm3 were randomly allocated to the individual groups (day 1) and subsequently treated on days 1, 8, 15 (V only) 22, and 29. After 5 weeks the following T/C values were recorded: group 1: 12.6%, 2: 80%, 3: 49%, 4: 42.8%, 5: 67%, 6: 49.2%, 7: 26.5%, 8: 45.5%. These results indicate a possible superiority of VMF over CMF, since the former exhibits little or no carcinogenicity at comparable therapeutic activity.

Animals↗