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Biomedical subjects

R Brehm

Publications and source records attributed to R Brehm.

At least 19 recordsLinked to original sources

Effects of human pituitary FSH isoforms on mouse follicles in vitro.

The effects of human FSH glycoforms on mouse follicle development and function in vitro were analysed, and an attempt was made to relate markers of follicular maturation to the expression of immunolocalized connexin (Cx) 43 and Cx26-based gap junctions. Three FSH fractions comprising discrete pI ranges [7.10-5.99 (pool I), pI 5.62-4.95 (pool II) and <3.75 (pool III)] were studied. Pool I produced the strongest effect on preantral granulosa cell proliferation and oestradiol production, and was highly effective for stimulating antral formation; this isoform also evoked a peripheral distribution of Cx43-containing gap junctions. Pool II was effective in promoting preantral granulosa cell proliferation but required higher FSH doses. This particular isoform provoked a more central distribution of Cx43-containing gap junctions, which was associated with a lower oestradiol production and less effective antral formation. Pool III was the least active for all markers of follicle development, and this was associated with minimal induction of Cx43-based gap junctions. The effects of the three FSH isoform pools on Cx26 expression were similar. The pattern of differences strongly suggests that FSH isoforms have complementary and specific actions on developing follicles, and that a shifting stage specific balance of isoforms is required for optimal follicle development.

Animals↗

Cellular localization of estrogen receptor-alpha (ERalpha) and -beta (ERbeta) mRNA in the boar testis.

Boar testes synthesize high amounts of estrogens which are known to stimulate several male sexual functions in a variety of extragonadal target tissues. Possible effects within the testis depend on the existence of the estrogen receptor subtypes alpha and beta (ERalpha, ERbeta). The precise cellular localization of these subtypes within the testis was, so far, based mainly on protein expression studies using different antibodies in several species including boars shows contradictory results. Therefore, we investigated the ERalpha and ERbeta gene expression using RT-PCR of testis homogenates and RT-PCR after UV-single cell microdissection combined with in-situ hybridization of four fertile boars with an average age of 32 weeks. Both ERalpha and ERbeta mRNA were found in testis homogenates. Using in-situ hybridization and UV-single cell microdissection ERalpha mRNA was present in type A and type B spermatogonia up to mid-pachytene primary spermatocytes in stage V-VIII and stage I of the seminiferous epithelial cycle, but not in other cells. ERbeta mRNA was found only in Sertoli cells. Interstitial Leydig cells revealed neither ERalpha nor ERbeta mRNA. The data suggest a direct impact of estrogen in the boar on Sertoli cell function via ERbeta and germ cell formation via ERalpha.

Animals↗

Gene signatures of testicular seminoma with emphasis on expression of ets variant gene 4.

Gene expression patterns of testicular seminoma were analysed applying oligonucleotide microarrays in 40 specimens of different tumour stages (pT1, pT2, pT3) and in normal testes. Transcripts of maternally expressed 3 transcripts were expressed in seminoma without correlation with delta-like 1 homologue expression indicating an impaired imprinting status in seminoma. Interestingly, the transcripts of bromodomain-containing 2 and nuclear autoantigenic sperm protein associated with spermatogenesis were significantly upregulated in progressing tumour stages. Transcription factors TEA domain family member 4 and ETS variant gene 4 (ETV4), weakly expressed in normal testis, were strongly augmented during tumourigenesis. For ETV4 expression, a significant correlation with the increased expression of matrix metalloproteinase 2 and a disintegrin and metalloproteinase domain 15 was determined. The ETV4 protein was localised to nuclei of spermatogonia and revealed an intense staining in seminoma cells. Taken together, we characterised additional transcription factors and spermatogenesis-associated genes involved in the progression of seminoma.

Adenovirus E1A Proteins↗

Regulation of Sertoli cell and germ cell differentation.

Unwanted childlessness affects approximately one in six couples worldwide. According to the World Health Organization, in nearly 40% of cases the cause can be attributed to the female, in 20% to the male, in 25% to both, and in 15% the cause remains unknown. The incidence of male factor infertility in the general population is approximately 7%. The majority of these men experience irreversible idiopathic infertility and cannot father children without some form of medical intervention. Male factor infertility, in addition, may be caused by testicular germ cell cancer, which is known to represent the most common cancer among young men in Western industrialized countries. There is growing evidence that this cancer originates from fetal germ cells exhibiting an aberrant programme of gene expression and that tumour progression may be favoured by an aberrant Sertoli cell-germ cell communication. The present monograph aims to shed more light on the regulation of Sertoli and germ cell differentiation. Involving knockout and transgenic mouse models, the authors focus on (a) male factor infertility that might be related to altered maturation of Sertoli cells, (b) male factor infertility that might be due to incorrect histone-to-protamine exchange in haploid spermatids, and (c) progression of testicular germ cell cancer that might be favoured by an aberrant Sertoli cell-germ cell communication.

Animals↗

Extracorporeal lipid elimination for treatment of gestational hyperlipidemic pancreatitis.

Gestational hyperlipidemia complicated by pancreatitis during the 24th week of gestation has been successfully managed by long-term extracorporeal elimination of triglyceride-rich lipoproteins. Three modes of treatment (plasma exchange, immunospecific apheresis, and a combination of both treatments) were compared for efficacy as therapy for metabolic derangements, altered blood rheology, and the loss of immunoglobulins. Treatments were performed by means of a peripheral venovenous approach. A combination plasma exchange/apheresis technique was highly effective; the loss of immunoglobulins remained acceptable. Clinical symptoms of pancreatitis subsided within 24 hours of the first treatment. A relapse during the 32nd week of gestation necessitated treatments more frequently than once a week. At the 36th week of gestation, after confirming lung maturity as indicated by a lecithin-sphingomyelin ratio of > 2.0, a cesarean section was performed. A healthy boy was delivered (2470 g; Apgar score, 9/10). This is the first report to show that long-term extracorporeal elimination of lipoproteins is a highly effective treatment of hyperlipidemic gestational pancreatitis.

Adult↗

Prophylactic perioperative use of clindamycin and metronidazole in vaginal hysterectomy without pelvic floor repair.

We studied the effect of perioperative clindamycin (3 x 600 mg in 100 ml 0.9% saline), metronidazole (3 x 500 mg in 100 ml 0.9% saline) and a placebo (3 x 100 ml of 0.9% saline) in 120 patients having a vaginal hysterectomy without colporrhaphy. The rate of postoperative urinary tract infections was significantly higher in the placebo group, but there was no significant difference between the three groups in the days of postoperative fever (a temperature above 37 degrees C) or in the length of hospital stay. One patient on placebo had a vault infection and another had a fever of unknown origin.

Adult↗

Muscarinic mobilization of choline in rat brain in vivo as shown by the cerebral arterio-venous difference of choline.

In anesthetized rats, the choline levels of cerebrospinal fluid and plasma obtained from blood collected from peripheral vessels (carotid artery, cardiac vessels) and from the transverse sinus were determined with a radioenzymatic assay. Cortical release of choline was studied using the "cup technique." The plasma choline level of the peripheral blood (11.5 mumol/L) was lower than that of the sinus blood. The resulting cerebral arterio-venous difference of choline was negative (3.2 mumol/L) and reflected the net release of choline from the whole brain. The plasma choline levels were not different irrespective of whether the rats were anesthetized with ether, urethane, or pentobarbital. However, the choline level of the cerebrospinal fluid, which normally was lower than the plasma choline levels, was increased by urethane anesthesia to a level between the arterial and venous plasma concentrations of the brain. In old rats (24 months), the choline level of the cerebrospinal fluid was significantly lowered, when compared with the results obtained with younger rats (2-4 months). In rats kept on a low-choline diet for 2 weeks, the plasma choline level of the peripheral blood was reduced to 51% of the control. The effect on the choline level of the sinus blood was smaller; the cerebral arterio-venous difference of choline was not reduced (it was even slightly enhanced). Likewise, the choline level of the cerebrospinal fluid and the cortical release of choline were not altered. Intraperitoneal administration of oxotremorine in pentobarbital-anesthetized rats kept on a low-choline diet increased the plasma levels of choline.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

Muscarinic mobilization of choline in rat cerebral cortex does not involve alterations of blood-brain barrier.

Efflux of choline from the rat cerebral cortex in vivo was investigated using the cup technique. After removal of the dura mater, the cup was placed on the cortex. Transmission and scanning electron microscopy revealed that the cortex was separated from the cup solution (100-300 microliter) by basal lamina, pia mater, arachnoid (with discrete defects) and remainders of the subdural neurothelium. Two kinds of experiments were carried out to determine: efflux of unlabelled choline into the cup solution; and translocation of radioactivity from the plasma into the cup solution (via blood-brain barrier and leptomeningeal layers) during i.v. infusion of [3H]choline or [14C]inulin. The former process was highly temperature-sensitive in contrast to the latter. Penicillin-G-sodium, which is known to damage the blood-brain barrier, was added to the cup solution, enhanced efflux of unlabelled choline, and caused a 5-fold increase in the rates of translocation of radioactivity during infusion of either labelled choline or inulin. In contrast, physostigmine (3 X 10(-4) M, added to cup solution) failed to enhance 3H-translocation, but markedly facilitated the efflux of unlabelled choline; this effect was highly temperature-sensitive and was blocked by atropine. It is concluded that activation of muscarinic receptors enhanced the choline efflux from cortical tissue. This effect was caused by cellular mobilization of choline presumably through an action on the metabolism of phosphatidylcholine. The effect was not due to alterations in the translocation of choline from the plasma to the cup solution, i.e. through permeability changes in the blood-brain barrier and in the leptomeningeal 'barrier'.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Serum plasminogen levels and timing of ovulation].

During diagnosis and treatment of female sterility, plasminogen and fibrinogen degraduation products were measured from patient's vein blood in the cycle of menstruation on the days round menstruation. On the days round ovulation and also before beginning of menstrual bleeding an elevated plasminogen level by unchanged fibrin(ogen) degraduation products was found. Therefore the plasminogen modulation as a causal factor for the rupture of follicles is discussed.

Anovulation↗

Hydrolysis, synthesis, and release of acetylcholine in the isolated heart.

The occurrence of unhydrolyzed acetylcholine (ACh) in the cardiac perfusate during vagal stimulation in the absence of cholinesterase inhibition has been demonstrated by several methods. Because some ACh was found unhydrolyzed in the extracellular space for several seconds after vagal stimulation (half-time of decay 2.5 s), it appears that the prolonged time course of the cardiac responses to bursts of vagal activity is determined by a slow rate of transmitter inactivation (diffusion plus hydrolysis) in addition to slowly operating postsynaptic mechanisms mediated by activation of the muscarinic receptor. The neuronal uptake of choline in isolated heart preparations was found to be Na+ dependent, sensitive to hemicholinium 3, and activated by vagal stimulation. Activation occurred after a delay of 1 or 2 min and slowly faded within 5 min after stimulation. Resting release of ACh was insensitive to extracellular Ca2+ and to muscarinic feedback inhibition, in contrast to the evoked transmitter release. Inasmuch as atropine increased ACh release by vagal and field stimulation to the same extent, muscarinic feedback inhibition is likely to occur at postganglionic parasympathetic neurons. Adrenergic agonists and propranolol did not significantly change the release of ACh.

Acetylcholine↗

[Initial description of hemoglobin D Punjab in an Austrian family].

Haemoglobin D Punjab was detected in a slightly overweight, but otherwise healthy pregnant woman when she was tested for gestational diabetes within the framework of a screening programme. Chromatographic evaluation of the haemolysate by high-pressure liquid chromatography (HPLC) revealed an unusual "splitting" of the A1 peak into two minor peaks. A diabetes-independent haemoglobin variant was suspected and further investigations, including electrophoresis, purification and sequential analysis of the tryptic peptide, identified the abnormal haemoglobin as haemoglobin D Punjab (beta 121 Glu-Gln). This is the first report of this haemoglobin variant in Austria. Various possible modes of geographical spreading of the gene from Punjab (India) are discussed, the land-route via Turkey being the most favourable hypothesis in this case. An investigation of 6 out of 7 living members of the family was undertaken. In 3 instances haemoglobin D Punjab was confirmed by HPLC and electrophoresis. The investigation of the family is currently being expanded to include a total of five generations.

Adult↗

[The infant of the diabetic mother. A current reevaluation (author's transl)].

In the past fifteen years several aspects of the diabetogenic fetopathia have changed. Tight metabolic control during pregnancy approaching normoglycemia was followed by a continuous decline in perinatal mortality. However, the evaluation of pregnancy outcome beyond statistical analyses still reveals some pertinent questions: They state to the increased incidence of congenital malformations, the pre- and postnatal diagnosis of significant gestational diabetes, the heterogeneity of impaired intrauterine growth and development and the late outcome of these children.

Congenital Abnormalities↗

[Monitoring of post-operative prevention of thrombosis by low dosage heparin with the radioactive iodine fibrinogen test (author's transl)].

In a prospective study low dosage subcutaneous heparin was administered to 148 patients after major gynaecological operations. The preventive effect on deep vein thrombosis was monitored by the radioactive iodine fibrinogen test. In 10.1% (15) of the cases higher than normal activity of the radioiodine fibrinogen test was detected. Only 4 patients (2.7%) had clinical signs of deep vein thrombosis. Because of the early occurrence of silent signs of deep vein thrombosis in the radioactive iodine fibrinogen test the onset of the subcutaneous heparin prophylaxis of thrombosis was shifted from the post-operative period to the pre-operative administration.

Adult↗

Total glycosylated hemoglobin in mothers of large-for-gestational-age infants: a postpartum test for undetected maternal diabetes?

Total glycosylated hemoglobin has been evaluated postpartum using a colorimetric (thiobarbituric acid: TBA) method in 50 mothers of large-for-gestational-age (LGA) infants (greater than 90th percentile by weight). 30 women without potential risk factors for chemical diabetes who gave birth to appropriate-for-gestational-age (AGA) infants formed the control group. When compared to the control mothers, mean total glycosylated hemoglobin (TBA color) levels were significantly higher in the mothers of LGA infants (p less than 0.01). 4 of the latter had an abnormal oral glucose tolerance test (GTT) done within 5 days postpartum and significantly elevated glycosylated hemoglobin compared to mothers of LGA infants with normal GTT (p less than 0.001). Furthermore, a significant linear correlation was found for mothers of LGA infants between TBA color levels and each of the following: fasting serum glucose (p less than 0.001), 1-hour serum glucose (p less than 0.001), 2-hour serum glucose (p less than 0.001), and infant birth weight (p less than 0.05). Analysis of TBA color levels early postpartum might be an alternative method for detecting unsuspected chemical diabetes in pregnancy.

Birth Weight↗

[Maternal hemoglobin AIc (HbAIc) and diabetic pregnancy (author's transl)].

Third trimester HbAIc was determined in 57 pregnant women according to the TBA-reaction, first discribed by Flückiger and Winterhalter (1976). Simultaneously oral glucose tolerance tests (GTT) were performed in 52 patients; in 5 insulin dependent diabetic women dayly blood sugar profiles 2 to 5 times per week were done throughout the third trimester. HbAIc, when expressed as per cent of total hemoglobin, was 6.14 +/- 0.56% (m +/- SD) in women with normal GTT (n = 40) and found to be significantly (p less than 0,001) elevated in 7 women with abnormal GTT (7.54 +/- 0.61%; m +/- SD) and in the 5 women with insulin dependent diabetes (7.59 +/- 0.92%; m +/- SD). In patients with abnormal and boarderline GTT a linear relation between HbAIc and mean blood sugar, as determined from individually summarized 60 and 120 minutes GTT values, was observed. Insulin dependent diabetic women with higher mean blood sugar (as calculated from the total profile values throughout 4 weeks prior to HbAIc determination) showed a tendency towards higher HbAIc values.

Blood Glucose↗