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C Brandt

Publications and source records attributed to C Brandt.

At least 73 records · Page 4Linked to original sources
PubMed1993

Baclofen prevents the increase of myocardial oxygen demand indexes evoked by the hypothalamic stimulation in rabbits.

The electrical stimulation of the paraventricular nucleus (PVN) of the hypothalamus in anaesthetized rabbits elicited important cardiovascular responses which were mainly characterized by increases in arterial pressure, dP/dtmax, and of the indexes of myocardial oxygen consumption, rate-pressure product (from 34 +/- 2 to 40 +/- 2 mmHg.bpm.10(-3) and triple product (from 102 +/- 12 to 162 +/- 19 mmHg2.s-1.bpm.10(-6). The hemodynamic alterations induced by PVN stimulation were similar to those observed during physical effort and stressful situations. Intracerebroventricular (0.1, 0.3 and 1 microgram.kg-1) or intravenous administration (1, 3 and 10 mg.kg-1) of baclofen, a selective GABAB receptor agonist, induced a dose-related decrease in the peak values of dP/dtmax and of the indexes of myocardial oxygen consumption (rate-pressure and triple products) during the electrical PVN stimulation. After 1 microgram.kg-1 baclofen (i.c.v.), the peak value of the triple product during PVN stimulation was 101 +/- 21 as compared to 149 +/- 15 before treatment. At the 10 mg.kg-1 dose (i.v.), the triple product during stimulation only reached 90 +/- 20 vs. 150 +/- 20 before treatment. These results suggested that a type B GABAergic transmission system is involved in the modulation of central control of the cardiac function. Drugs modulating this system could therefore be designed to blunt the myocardial oxygen demand increases.

Animals↗
PubMed1993

Assignment of an autosomal sex reversal locus (SRA1) and campomelic dysplasia (CMPD1) to 17q24.3-q25.1.

We have mapped the autosomal sex reversal locus, SRA1, associated with campomelic dysplasia (CMPD1) to 17q24.3-q25.1 by three independent apparently balanced de novo reciprocal translocations. Chromosome painting indicates that the translocated segment of 17q involves about 15% of chromosome 17 in all three translocations, corresponding to a breakpoint at the interphase between 17q24-q25. All three 17q breakpoints were localized distal to the growth hormone locus (GH), and proximal to thymidine kinase (TK1). Due to the distal location of the breakpoints, previously mentioned candidate genes, HOX2 and COL1A1, can be excluded as being involved in CMPD1/SRA1. The mouse mutant tail-short (Ts) which maps to the homologous syntenic region on mouse chromosome 11, displays some of the features of CMPD1.

Abnormalities, Multiple↗
PubMed1993

The management of common bile duct stones in patients undergoing laparoscopic cholecystectomy.

The management of suspected and/or unsuspected common bile duct (CBD) stones in patients undergoing laparoscopic cholecystectomy (LC) is controversial. Decisions on whether to perform an open CBD exploration versus employing therapeutic options such as preoperative/post-operative endoscopic retrograde cholangiography (ERCP) or endoscopic duct exploration are polemic. To determine indications, timing, benefits, and potential morbidity of these approaches, we gathered data on 401 patients undergoing LC within the last 18 months. Indications for preoperative ERCP included jaundice (40%), dilated ducts (28%), elevated amylase (19%) or alkaline phosphatase (21%), suspicion of CBD stones by ultrasound (17%) and "other" (17%). Indications for postoperative ERCP were retained stones (33%) and CBD evaluation (67%). Indications for CBD exploration included abnormal cholangiogram (64%), palpable stones (18%), and other (18%). A significant correlation was observed between suspected stones by ultrasound and stones found by ERCP (P < 0.01). For patients in the "other" category, preoperative ERCP was universally negative (P = 0.04). Overall ERCP morbidity was 4/59 (6.8%), and the overall failure rate for clearing CBD stones was 2/28 (7.1%). The timing of the ERCP did not affect morbidity/mortality. Multivariate analysis revealed that age (P << 0.001), the presence of pre-existing medical risk factors (P << 0.001), and duration of LC (P = 0.0034), but not ERCP (P = 0.08), were the important factors determining LC morbidity. In summary, common bile duct stones can be successfully cleared endoscopically in the majority of patients undergoing LC. Patients with suspected CBD stones should undergo pre-operative ERCP, and strict criteria should be applied in the selection of these patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

Adenine nucleotide-induced inhibition of binding of sulphonylureas to their receptor in pancreatic islets.

1. The effects of the Mg complex of adenosine 5'-triphosphate (MgATP) on binding of sulphonylureas to microsomes obtained from mouse pancreatic islets were examined. 2. MgATP inhibited the binding of both glibenclamide and tolbutamide to microsomes. 3. Binding of [3H]-glibenclamide inhibited by MgATP was not further diminished by Mg(2+)-bound adenosine 5'-(beta, gamma-imidotriphosphate) (AMP-PNP) or free adenosine 5'-diphosphate (ADP). Higher concentrations of MgAMP-PNP induced a partial reversal of the inhibitory effect of MgATP on [3H]-glibenclamide binding. 4. The apparent dissociation constant (K'D) for binding of [3H]- glibenclamide remained constant when 5. Extracellular ADP did not markedly stimulate insulin release from mouse pancreatic islets. 6. It is concluded that sulphonylureas and cytosolic nucleotides exert their inhibitory effects on the K-ATP-channels of beta-cells by binding to different sites. The binding properties of the sulphonylurea receptor seem to be modulated by protein phosphorylation.

Adenine Nucleotides↗
PubMed1992

Effect of MgATP on pinacidil-induced displacement of glibenclamide from the sulphonylurea receptor in a pancreatic beta-cell line and rat cerebral cortex.

1. The effects of blockers and openers of K+ channels on binding of [3H]-glibenclamide to microsomes obtained from a pancreatic beta-cell line (HIT-T15) or rat cerebral cortex were examined. 2. The blockers quinine, chlorpromazine and thiopentone and the openers cromakalim [(+/- ) 6-cyano-3,4-dihydro-2,2-dimethyl-trans-4-(2-oxo-1- pyrrolidyl)-2H-benzo[b]pyran-3-ol] and minoxidil sulphate did not significantly interact with the sulphonylurea receptor of HIT-cells both at phosphorylating (presence of MgATP) and dephosphorylating (absence of MgATP) conditions. 3. In the absence of MgATP, pinacidil (200-500 microM) did not significantly displace [3H]-glibenclamide binding to microsomes from HIT-cells. The displacement of [3H]-glibenclamide binding was strongly enhanced by MgATP and was due to a decrease in the number of high affinity binding sites for glibenclamide. 4. MgATP enhanced pinacidil-induced inhibition of [3H]-glibenclamide binding to microsomes from rat cerebral cortex. 5. The effect of MgATP on pinacidil-induced inhibition of [3H]-glibenclamide binding was maintained after solubilization of the membranes from HIT-cells or rat cerebral cortex. 6. It is concluded that the sulphonylurea receptor is regulated not only by sulphonylureas but also by the K+ channel openers, diazoxide and pinacidil, and by protein phosphorylation. The binding sites for sulphonylureas and these K+ channel openers are not identical, but appear to be located at a single protein or at tightly associated proteins.

ATP-Binding Cassette Transporters↗
PubMed1992

The binding properties of the solubilized sulfonylurea receptor from a pancreatic B-cell line are modulated by the Mg(++)-complex of ATP.

Previous studies demonstrated that the Mg complex of ATP decreases glyburide- and increases diazoxide-binding to membranes from pancreatic islets. To examine further the mechanism of these effects, the sulfonylurea receptors in microsomes of the hamster B-cell line HIT-T15 were solubilized with detergents. Maximum recovery of receptors (40%) was obtained with Triton X-100. Specific binding of [3H]glyburide to the solubilized receptors (Kd = 0.35 nM, maximum number of binding sites = 170 fmol/mg of protein) corresponded well to specific binding to microsomes. In Triton X-100 extracts, MgATP (300 microM) reduced the number of high-affinity sites for [3H]glyburide by 50% and increased the dissociation constant for [3H]glyburide by 4-fold; MgATP was half-maximally effective at 20 microM. Development of MgATP-induced inhibition of [3H]glyburide binding to solubilized binding sites was not slower than dissociation of [3H]glyburide binding. Alkaline phosphatase accelerated the reversal of MgATP-induced inhibition of [3H]glyburide binding. In the presence of Mg++, not only ATP but also ADP, GTP and GDP inhibited [3H]glyburide binding to the solubilized receptor. However, MgADP did not inhibit [3H]glyburide binding when the MgATP concentration was kept low by the hexokinase reaction. MgATP significantly enhanced diazoxide-induced displacement of [3H]glyburide from the solubilized receptor. The MgATP-induced inhibition of binding was weakened by millimolar concentrations of free ATP. It is concluded that the binding sites for MgATP, glyburide and diazoxide are located at a single protein or at closely associated proteins which may include a protein kinase.

ATP-Binding Cassette Transporters↗
PubMed1992

[Hepatic elimination of thiopental in heart surgery patients].

Thiopental is a hypnotic drug that is widely used for the induction of anaesthesia. The mechanism of the short-term action is based on the rapid distribution of the drug, and in contrast to methohexital, the metabolism of thiopental is not relevant in use in conditions of operative anaesthesia. However, in neurotraumatology thiopental is frequently used as continuous infusion for several days to reduce cerebral metabolism. Under these circumstances, the elimination of thiopental becomes the most important factor for the duration of action. In order to clarify the relative contribution of the liver to the disposition of thiopental, hepatic blood flow was measured during the induction of anaesthesia and at sternotomy combined with the determination of plasma concentrations of the drug in arterial and hepatic venous blood, making it possible to calculate the hepatic and total plasma clearance of thiopental. METHOD. The study was thoroughly discussed and approved by the local ethics committee, and all patients gave informed written consent. The investigation was performed in 10 male patients (as detailed in Table 1), who had been referred for elective coronary artery bypass surgery. The determination of hepatic plasma flow was performed by the indocyanine green (ICG) infusion extraction technique using liver vein catheterization. Before induction of anaesthesia (MP1), after induction (MP2) and at sternotomy (MP3), hemodynamic data (heart rate, arterial pressure, cardiac output) were recorded and blood samples for the determination of hepatic plasma flow by the concentration of ICG were collected. Additionally, arterial and hepatic venous plasma concentrations of thiopental were determined by gas chromatography after induction until the extracorporeal circulation was started. Anaesthesia was induced with a bolus dose of thiopental 4 mg/kg body wt, fentanyl 7 micrograms/kg and pancuronium 0.1 mg/kg and maintained with a continuous infusion of fentanyl 20 micrograms/min and mechanical ventilation with O2/N2O at an FiO2 of 0.5. RESULTS. Median arterial pressure (MAP) decreased from 89 mmHg to 74 mmHg after induction and rose again to reach 104 mmHg at sternotomy. Cardiac output (HZV) also decreased from 6.17 l/min to 4.76 l/min after induction, but remained unchanged at sternotomy (Table 2). Hepatic plasma and blood flow showed no significant changes but tended to decrease after the induction of anaesthesia. Hepatic blood flow was constantly 26-28% of cardiac output. In the same way, intestinal oxygen consumption (VO2) did not change significantly, but the tendency was identical to that with hepatic perfusion. Hepatic clearance of thiopental as the product of hepatic extraction of thiopental (with a median value of 0.29) and hepatic plasma flow was 0.21 l/min. CONCLUSIONS. Thiopental is subject to a relatively low hepatic extraction of 0.29. Thus, changes in hepatic perfusion do not influence the elimination of thiopental. The actions of thiopental on global hemodynamics are comparable with the results found in the literature, characterized by a significant reduction in MAP and cardiac output after induction. The hepatic clearance of thiopental found in this study, with an absolute value of 0.21 l/min, is absolutely comparable with the data for total-body clearance reported in the literature. It is concluded that the liver is the only organ responsible for the elimination of thiopental in humans.

Adult↗
PubMed1991

Genes involved in meso-diaminopimelate synthesis in Bacillus subtilis: identification of the gene encoding aspartokinase I.

Thermosensitive mutants of Bacillus subtilis deficient in peptidoglycan synthesis were screened for mutations in the meso-diaminopimelate (LD-A2pm) metabolic pathway. Mutations in two out of five relevant linkage groups, lssB and lssD, were shown to induce, at the restrictive temperature, a deficiency in LD-A2pm synthesis and accumulation of UDP-MurNAc-dipeptide. Group lssB is heterogeneous; it encompasses mutations that confer deficiency in the deacylation of N-acetyl-LL-A2pm and accumulation of this precursor. Accordingly, these mutations are assigned to the previously identified locus dapE. Mutations in linkage group lssD entail a thermosensitive aspartokinase 1. Therefore, they are most likely to affect the structural gene of this enzyme, which we propose to designate dapG. Mutation pyc-1476, previously reported to affect the pyruvate carboxylase, was shown to confer a deficiency in aspartokinase 1, not in the carboxylase, and to belong to the dapG locus, dapG is closely linked to spoVF, the putative gene of dipicolinate synthase. In conclusion, mutations affecting only two out of eight steps known to be involved in LD-A2pm synthesis were uncovered in a large collection of thermosensitive mutants obtained by indirect selection. We propose that this surprisingly restricted distribution of the thermosensitive dap mutations isolated so far is due to the existence, in each step of the pathway, of isoenzymes encoded by separate genes. The biological role of different aspartokinases was investigated with mutants deficient in dapE and dapG genes. Growth characteristics of these mutants in the presence of various combinations of aspartate family amino acids allow a reassessment of a metabolic channel hypothesis, i.e. the proposed existence of multienzyme complexes, each specific for a given end product.

Aspartate Kinase↗
PubMed1989

[Medical rehabilitation from the viewpoint of the established physician].

In view of the not inconsiderable numbers of pension insured who have undergone no medical rehabilitation prior to their being pensioned prematurely, the principle of "rehabilitation comes before pensioning" hence not being implemented for this population, it is deemed justified to inquire into the causes of this situation. In the framework of the present study of 902 questionnaires returned by office practice physicians, it is presumed that the office practice physician is the controlling agent in inducing appropriate patients at the right time to participate in a rehabilitation measure. The following indicators are presumed to decisively influence this steering function: Attitude towards medical rehabilitation; Disease/disability-specific experience with medical rehabilitation measures; Satisfaction with the rehabilitation clinic selected by the pension insurance administration; Awareness of the rehabilitation clinics' range of rehabilitative services and the various treatment modalities available; Awareness of pertinent legal provisions; Cooperation between office-practice physician and pension insurance administration.

Attitude of Health Personnel↗
PubMed1987

Thermosensitive Bacillus subtilis mutants which lyse at the non-permissive temperature.

A collection of 655 thermosensitive mutants of Bacillus subtilis 168, obtained by indirect selection, was screened for those lysing at the non-permissive temperature. Thirty-three mutations thus identified were distributed by transformation into eight linkage groups designated lssA to lssH. The distribution was non-random. With the exception of group A, all groups were small, suggesting that mutations identified in each of them may map in one gene only. Linkage groups identified here were mapped in four different regions of the B. subtilis chromosome and their positions relative to reference markers were the following: (i) aroI-lssA-dal-purB; (ii) metC-lssB-lssC-furA-pyrE-cysC-lssD; (iii) lssF-gtaA-lssG-hisA-lssH-cysB; and (iv) cysA-lssE-dnaC-purA. Kinetics of N-acetyl-D-[1-14C]glucosamine incorporation revealed that groups A, B, C, D and F are deficient in peptidoglycan synthesis at the restrictive temperature. In group G, anomalies at the cell wall level were suggested by incorporation and growth curves. It appears that in almost all known cases, thermosensitive lysis mutations in B. subtilis either affect genes involved in peptidoglycan synthesis or lead, more or less directly, to induction of prophages.

Bacillus subtilis↗
PubMed1987

Inhibitory Effects of a Pectin-Enriched Tomato Cell Wall Fraction on Agrobacterium tumefaciens Binding and Tumor Formation.

A pectin-enriched soluble cell wall fraction (CWF) prepared from suspension cultured tomato cells inhibits binding of Agrobacterium tumefaciens to these cells. It was hypothesized that the CWF contains the plant surface binding site for A. tumefaciens (NT Neff, AN Binns 1985 Plant Physiol 77: 35-42). Experiments described here demonstrate that tomato CWF inhibited tumor formation on potato slices and Agrobacterium binding to intact tomato cells in a dose-dependent fashion. Boiling the fraction reduced both its binding and tumor inhibitory activities. Tumor inhibitory activity was titrated out by increased concentrations of bacterial inocula with no inhibition apparent at 1 x 10(8) bacteria per milliliter. These results indicate that a tomato CWF is enriched for a putative A. tumefaciens binding site which may also be involved in tumor formation in potato.

Journal Article↗
PubMed1985

Detection of enteric adenoviruses by dot-blot hybridization using a molecularly cloned viral DNA probe.

Enteric adenoviruses (EAds) (candidate adenoviruses 40 and 41, subgroups F and G) have been implicated in the etiology of gastroenteritis in infants, but their clinical significance has been unclear because a rapid test to distinguish these agents from other adenovirus (Ad) types has not been available. We developed a dot-blot hybridization assay for EAd DNA using a cloned DNA fragment that has little homology to non-EAd DNAs. The dot-blot system detected less than 20 pg of EAd DNA, while showing minimal cross hybridization to representative strains from all other Ad groups. There was no detectable hybridization to extracts of samples known to contain other enteric viruses. It was further shown that low levels of EAds in specimens could be amplified by culturing for 1 day in 293 cells. Stool samples and tissue culture lysates prescreened by electron microscopy, cell culture or ELISA were tested in a blind fashion. Using endonuclease analysis as the standard for typing the isolates, we found the dot-blot system to have a 91% sensitivity and 71% specificity for detecting EAds and distinguishing them from other Ads. False-positive and equivocal dot-blot results appeared to be caused by other Ads.

Adenoviridae Infections↗
PubMed1985

Factors influencing the activity of dimethylnitrosamine demethylase in hamster, rat and chicken liver microsomes.

In vitro metabolism of dimethylnitrosamine (DMN) by liver microsomal fractions of hamster, rat and chicken revealed that the three species under certain assay conditions, were capable of metabolizing DMN at different rates (hamster greater than rat greater than chicken). The magnitude of the demethylase activity was found to be dependent on the nature of the buffer, the concentration of cytochrome P-450 (P-450) and the concentration of the substrate DMN. Enzyme activity was higher in Hepes buffer than in the phosphate buffer. Concentrations of phosphate higher than 20 mM inhibited the activity of the rat and chicken enzymes. This effect of phosphate was not a consequence of increase in ionic strength since KCl over a wide range of concentration failed to inhibit the activity.

Animals↗