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Biomedical subjects

R Brandt

Publications and source records attributed to R Brandt.

At least 19 recordsLinked to original sources
PubMed1992

Purification of a mammary-derived growth inhibitor (MDGI) related polypeptide expressed during pregnancy.

The present study was undertaken to screen immunochemically for MDGI-related proteins in the mammary gland. A new form, MDGI 2, not present in lactation could be detected in the bovine gland during pregnancy. It was further distinguished from MDGI by its lower molecular weight, its association with a complex binding to WGA, and by lacking immunoreactivity to an anti-MDGI antibody directed against the C-terminus of MDGI. MDGI 2 was purified by chromatography over DEAE-Sepharose, Bio-Gel P-30 in 1% acetic acid, Sephacryl S-200 in 6 M urea and Mono Q. Final purification included HPLC on TSK G-3000 SW and electroelution from SDS-gels. Cell-free translation of poly (A+)mRNA from glands of pregnant animal yielded one form identical with MDGI. We assume that posttranslational processing of MDGI is involved in its activities.

Animals↗
PubMed1992

Comparative binding of etretinate and acitretin to plasma proteins and erythrocytes.

The interactions of etretinate and its main metabolite acitretin with human plasma proteins have been investigated in vitro by an erythrocyte partitioning technique that allows a quantitative estimation of the plasma and erythrocyte binding. Etretinate was extensively lipoprotein-bound (75% of plasma etretinate), with a binding constant for its main low density lipoprotein carrier of 40 x 10(6) M-1, accounting for 48% of the total plasma-bound drug. Acitretin was mainly albumin-bound (91% of plasma acitretin), with a binding constant of 0.7 x 10(6) M-1. The total plasma binding of both drugs was > 99% and, in blood, the fractions associated with erythrocytes were 14.5 and 8.1% of the total amount for etretinate and acitretin, respectively.

Acitretin↗
PubMed1992

Ribosomal localization of the mRNA in the 30S initiation complex as revealed by UV crosslinking.

Translation initiation complexes consisting of 30S ribosomal subunits, 32P-labelled mRNA (002 mRNA), fMet-tRNA and the three initiation factors were subjected to UV-crosslinking to determine the protein and rRNA neighbors of the bound mRNA by immunochemical methods and by nucleic acid hybridization techniques. The mRNA was found to be crosslinked to a specific region of the 16S rRNA spanning from nucleotide 418 to 615 and to ribosomal proteins S1 and S21 (the main targets), S3, S10, S12 and S14; a low level of crosslinking was also detected with S2, S7, S13, S18 and S19.

Base Sequence↗
PubMed1992

Circulating hyaluronic acid in nonpregnant, pregnant, and postpartum guinea pigs: elevated levels observed at parturition.

OBJECTIVE: Dilatation of the uterine cervix at parturition is associated with an increase in cervical hyaluronic acid content. The objective is to test the hypothesis that circulating hyaluronic acid is increased at parturition. STUDY DESIGN: Serum hyaluronic acid levels from nonpregnant (n = 5), pregnant (n = 13), and postpartum (n = 4) adult Hartley guinea pigs were determined with a radiometric assay that utilizes iodine 125-labeled hyaluronic acid-binding protein. Results were analyzed for statistical significance with Student's paired t test and regression analysis. RESULTS: The serum hyaluronic acid level in nonpregnant animals was 238 +/- 88 ng/ml (mean +/- SEM). During pregnancy, serum hyaluronic acid levels were 127 +/- 12 and 126 +/- 34 ng/ml at 25 and 50 to 63 days' gestation, respectively. At parturition, hyaluronic acid levels increased fivefold to 765 +/- 111 ng/ml (p less than 0.001). Hyaluronic acid levels returned to antepartum values 2 days post partum (153 +/- 27 ng/ml). There was no significant difference between arterial and venous levels. CONCLUSION: Circulating hyaluronic acid levels increase significantly at parturition in the guinea pig.

Animals↗
PubMed1991

Ribosome-mRNA contact sites at different stages of translation initiation as revealed by cross-linking of model mRNAs.

Two model mRNAs, one with and one without the Shine-Dalgarno (SD) sequence, were bound to Escherichia coli 30S ribosomal subunits in the presence and absence of initiation factors and initiator tRNA and then cross-linked by diepoxybutane. The distribution of the cross-linked mRNA among rRNA and ribosomal proteins (r-proteins) and the extent to which individual r-proteins react was found to be affected by the presence or absence of the SD sequence and by the initiation factors and initiator tRNA. The results are consistent with the hypothesis that the position of the 30S-bound mRNA is shifted under the influence of the initiation factors and fMet-tRNA from a stand-by position towards a second site where the decoding of the initiation triplet by the initiator tRNA occurs.

Binding Sites↗
PubMed1991

Effects of environmental temperature on the venodilatory response to nitroglycerin.

The venodilatory response to nitroglycerin (0.8 mg sublingually) was measured in 10 healthy young male volunteers in a cool [24.3 +/- 0.6 degrees C skin temperature (Tsk)] and a warm environment (34.7 +/- 0.2 degrees C Tsk). Nitroglycerin caused mean arterial pressure to fall and heart rate to rise in both the cool (105 +/- 2 to 96 +/- 3 mmHg; 55 +/- 3 to 62 +/- 3 beats/min) and the warm environment (87 +/- 3 to 81 +/- 3 mmHg; 66 +/- 4 to 75 +/- 3 beats/min), but the fall in pressure was greater in the cool than in the warm environment. Forearm blood flow was reduced and forearm vascular resistance elevated in the cool (117 +/- 19 units; 1.15 +/- 0.08 ml.100 cc arm-1.min-1) compared with the warm environment (15 +/- 3 units; 8.60 +/- 1.89 ml.100 cc arm-1.min-1). Nitroglycerin caused forearm vascular resistance to fall in the cool but had no effect in the warm environment. Venous distensibility (increase in venous volume per 30-mmHg increase in venous pressure) was twice as great in the warm as in the cool environment (3.90 +/- 0.27 vs. 1.88 +/- 0.23 ml/100 cc arm). However, the venodilatory effect of nitroglycerin was similar in the cool and warm environments (0.79 +/- 0.10 vs. 0.67 +/- 0.13 ml/100 cc arm, respectively). Arterioles are not dilated by nitroglycerin in the warmer environment, but the venodilatory effect of nitroglycerin is quantitatively similar in the two environments.

Adult↗
PubMed1991

[Effects of the PAF antagonist WEB 2086 on hypoxia and angiotensin II-induced pulmonary vasoconstriction in the isolated perfused rat lung].

Using isolated blood-perfused lung preparations of rats, we tested the influence of the PAF antagonist WEB 2086 on vasoconstriction triggered by hypoxia or angiotensin II (A II). If a constant flow was pre-set, changes in the prepulmonarily measured pressure were directly related to the changes of resistance in the pulmonary flow. WEB 2086 reduced the hypoxically conditioned vasoconstriction (HPV) when using blood as perfusion medium, the effect being dependent on the dose (ED50 = 127.3 +/- 21.1 mg/l). HPV was lowered on the average by 82% if the full pharmacologic dose of 800 mg/l WEB 2086 was added to the perfusate. The A II response was weakened to a lesser degree (by 45%). If plasma was used as perfusate, the pressure increase in response to hypoxic stimulation or A II was less marked. However, the relative effect of the PAF antagonist was analogous (attenuation by 83% or 53%, respectively). In chronically hypoxic animals (3 weeks at 10% O2) the relative pressure drop in the lesser circulation after application of WEB 2086 (400 mg/l; HPV; blood as perfusate) was definitely more pronounced (p less than 0.001). The fact that WEB partly antagonises the pulmonary vasoconstriction triggered both by alveolar hypoxy and by angiotensin II, seems to indicate that in both constrictive stimuli PAF participates in the complex mediator mechanism or that WEB 2086 exercises a non-specific vasodilatory effect on the pulmonary flow.

Angiotensin II↗
PubMed1990

Inflammation and cartilage metabolism in rheumatoid arthritis. Studies of the blood markers hyaluronic acid, orosomucoid, and keratan sulfate.

Single analyses of peripheral blood of rheumatoid arthritis (RA) patients showed a significant reduction in the mean value for keratan sulfate (KS) compared with that in control subjects, but the mean value for orosomucoid (OM) was elevated compared with that in control subjects. Some RA patients displayed highly elevated levels of hyaluronic acid (HA), while others exhibited normal levels. There was a significant inverse correlation between OM and KS content in RA patients, as well as a direct correlation between HA and OM. In longitudinal studies of RA patients, parallel changes in OM and HA and inverse changes between KS and OM or HA were commonly observed. Clinical analyses revealed that there was an inverse correlation between KS and morning stiffness, and direct correlations between the number of tender joints and HA, and between HA or the erythrocyte sedimentation rate and the number of joints with effusions. The reason(s) for the inverse correlation between KS and OM as an index of systemic inflammation remains to be established. Circulating HA represents an index of joint inflammation, for which a marker has not been previously available.

Adult↗
PubMed1990

Water and electrolytes in muscle tissue and free amino acids in muscle and plasma in connection with transurethral resection of the prostate. I. Distilled water as an irrigating fluid.

10 patients undergoing transurethral resection of the prostate using sterile distilled water as an irrigating fluid were studied. The extra- and intracellular distribution of water, the total content of water and electrolytes and the free amino acid concentrations in muscle tissue were determined together with the concentrations of free amino acids in plasma preoperatively, immediately postoperatively and 2 hours postoperatively. The content of water and concentrations of electrolytes in skeletal muscle did not change significantly from the preoperative to the postoperative period with the exception of the potassium concentration, which decreased 2 hours postoperatively. The following free amino acid concentrations in muscle tissue showed significantly decreased values 2 hours postoperatively compared with the preoperative values: taurine, serine, glutamate, proline and leucine. The concentrations of non-essential amino acids in muscle decreased significantly 2 hours postoperatively. This may be interpreted as a dilution effect. An increased concentration of some amino acids in plasma postoperatively may be explained as a haemoconcentration effect due to the use of a postoperative diuretic.

Aged↗
PubMed1990

DQ beta restriction fragment length polymorphism in insulin dependent diabetes mellitus.

HLA DQ beta restriction fragment length polymorphisms (RFLP's) were compared in 43 patients with insulin dependent diabetes mellitus (IDDM), 51 healthy first grade relatives of IDDM patients and 27 controls without IDDM heredity in their families. We were able to demonstrate an association between the presence of a 12 kb BamHI restriction fragment (p less than 0.001) and 12 kb/4 kb (p less 0.01) or 12 kb/4.4 kb (p less than 0.001) BamHI fragment combinations and IDDM. But for these fragments and fragment combinations we also found increased frequencies in the healthy first grade relatives of IDDM patients. That means for the evaluation of the importance of the characterised "risk fragments" in practice it is necessary to follow up the manifestation of IDDM in this risk group.

Adolescent↗
PubMed1989

Adenosine receptor mediated stimulation of ventilation in man.

We wanted to examine how adenosine stimulates ventilation in man. Bolus doses of adenosine were given i.v. in an antebrachial vein in multiples of 2.65 mg. The minute ventilation was increased by adenosine 5.3 to 15.9 mg (median values) from control 12.6 +/- 1.9 l min-1 to 42.5 +/- 4.7 l min-1 in a dose-dependent manner. The adenosine receptor antagonist theophylline, 58.3 +/- 3.3 (mean +/- SEM) mumol l-1 plasma, inhibited the response by approximately 25%. Dipyridamole 10 mg, an adenosine uptake blocker, enhanced the effect of adenosine by approximately 60%. The ventilation was not affected by metoprolol, atropine, naloxone or cromolyn sodium but was attenuated by hyperventilation. The respiratory stimulation started before chest pain and cardiovascular effects such as AV-block were encountered. It is concluded that this respiratory stimulation shows characteristics of adenosine receptor mediated responses but the location of such adenosine receptors is uncertain. The findings are compatible with a stimulatory or facilitating effect of adenosine on afferent pathways.

Adenosine↗
PubMed1989

Pharmacokinetics and metabolism of intravenous and oral fleroxacin in subjects with normal and impaired renal function and in patients on continuous ambulatory peritoneal dialysis.

The pharmacokinetics of fleroxacin, including the formation of N-demethyl and N-oxide fleroxacin after the administration of single intravenous (100-mg) and oral (400-mg) doses, was investigated in 26 subjects with various levels of renal function, including 7 patients on continuous ambulatory peritoneal dialysis. Fleroxacin was well tolerated by all subjects. The volume of distribution, systemic availability, and peak concentration after the administration of oral fleroxacin were independent of the glomerular filtration rate. As a consequence of a declining renal clearance but not nonrenal clearance, the total body clearance of fleroxacin declined with decreasing glomerular filtration rate from 1.41 +/- 0.23 ml/min per kg in subjects with normal renal function to 0.58 +/- 0.13 ml/min per kg in patients with end-stage renal disease (r = 0.84, P less than 0.001). The analysis revealed that the N-oxide metabolite exhibited formation-limited kinetics and the N-demethyl metabolite exhibited elimination-limited kinetics. The areas under the curve of both metabolites increased with declining renal function. In patients on continuous ambulatory peritoneal dialysis the mean dialysate/plasma concentration ratio of fleroxacin increased from 0.52 +/- 0.11 to 0.71 +/- 0.13 (P less than 0.001) with increasing dwell time, resulting in a 7.8 +/- 3.6% recovery of unchanged fleroxacin in peritoneal dialysate. In conclusion, (i) a 50% reduction of the maintenance dose is recommended in patients with a renal function below 20 to 30 ml/min per 1.73 m2, and (ii) therapeutic concentrations of fleroxacin in the peritoneal dialysate should be achievable after oral administration in patients on continuous ambulatory peritoneal dialysis.

Administration, Oral↗
PubMed1988

A 13-kilodalton protein purified from milk fat globule membranes is closely related to a mammary-derived growth inhibitor.

With the use of specific antibodies against a previously purified [Boehmer, F.-D., Lehmann, W., Schmidt, H., Lange, P., & Grosse, R. (1984) Exp. Cell Res. 150, 466-477] and sequenced mammary-derived growth inhibitor (MDGI) [Boehmer, F.-D., Kraft, R., Otto, A., Wernstedt, C., Hellmann, U., Kurtz, A., Mueller, T., Rohde, K., Etzold, G., Lehmann, W., Langen, P., Heldin, C.-H., & Grosse, R. (1987) J. Biol. Chem. 262, 15137-15143], the localization and relative amount of immunoreactive 13-kilodalton (kDa) antigen in different fractions of bovine milk were determined. The highest amount of antigen was found to be associated with the milk fat globule membranes (MFGM). As revealed by a dot immunobinding assay, the amount of immunoreactive bovine and human MFGM-associated antigen increased dramatically with the onset of lactation after delivery. This finding corresponds to earlier data obtained for MDGI and indicates a relationship between the proliferative state of mammary epithelial cells and the amount of immunoreactive antigen. The 13-kDa antigen has been purified from MFGM to homogeneity by preparative sodium dodecyl sulfate-polyacrylamide gel electrophoresis and electroelution. The MFGM-derived 13-kDa polypeptide was found to be almost identical with MDGI as demonstrated by tryptic digestion and partial amino acid sequence analysis of tryptic fragments of both proteins. The results clearly show the presence of a membrane-bound MDGI-related 13-kDa protein, thus supporting the possible involvement of membrane-associated growth inhibitors in growth regulation of mammary epithelial cells.

Amino Acid Sequence↗
PubMed1988

Pharmacokinetics of cefetamet (Ro 15-8074) and cefetamet pivoxil (Ro 15-8075) after intravenous and oral doses in humans.

This report summarizes the results of three pharmacokinetic studies of cefetamet and cefetamet pivoxil conducted in normal adult male volunteers. In the first study the pharmacokinetics of cefetamet were evaluated after intravenous infusion of doses ranging from 133 to 2,650 mg. Over this dose range, the pharmacokinetics were linear. A dose-proportional increase in the area under the curve from zero to infinity was observed, whereas total clearance (140.3 +/- 23.6 ml/min), renal clearance (130.3 +/- 18.2 ml/min), volume of distribution at steady state (0.288 +/- 0.023 liter/kg), fraction excreted unchanged in the urine (94 +/- 11%), and elimination half-life (2.07 +/- 0.18 h) were independent of dose. In a second study the absolute bioavailability of single 1,500-mg doses of a tablet formulation of the pivaloyloxymethylester of cefetamet was evaluated under conditions of fasting and after a standard breakfast. Administration with food increased the extent of absorption (from 31 +/- 7 to 44 +/- 4%) while decreasing the rate of absorption (time to maximum concentration of drug in plasma increased from 3.0 +/- 0.6 to 4.8 +/- 0.4 h). The third study consisted of multiple oral administration of 1,000 mg of a similar oral tablet formulation twice daily for 10 days. This regimen was preceded and followed by intravenous administration of a 500-mg bolus dose of cefetamet. Oral doses were administered with breakfast and dinner. The absolute bioavailability of the tablet formulation was assessed after the first dose and after both the morning and the evening doses on day 10 of oral therapy. The compound was consistently absorbed to the extent of approximately 50% with no significant differences observed between the morning and evening doses on day 10.

Administration, Oral↗