Once-daily versus multiple-daily gentamicin in infants and children.

In this prospective randomized trial, the efficacy and safety of once-daily administration of gentamicin were compared with multiple-daily administration in infants and children. In addition, pharmacokinetic variables were calculated. Gentamicin therapy was started at a dose of 5 mg/kg per day under individual dose or dosage interval adjustments to achieve target levels.

Transcription of mutS- and mutL-homologous genes during meiosis in Saccharomyces cerevisiae and identification of a regulatory cis-element for meiotic induction of MSH2.

We have analysed the levels of mRNA transcripts of the mutS- and mutL-homologous genes of the yeast Saccharomyces cerevisiae during the course of meiosis, by quantitative RT-PCR. We found that all mutS homologues (MSH1-6) were induced during meiosis, whereas no evidence for regulation of the mutL homologues (PMS1, MLH1-3) was obtained. Temporal expression patterns indicative of co-regulation were observed for the gene pairs MSH4/MSH5 and MSH2/ SPO11.

Synchronous bladder augmentation and living related kidney transplantation.

Ileocystoplasty for enlargement of bladder capacity in conjunction with renal transplantation has been described in several cases. However, the surgical approach has been accomplished as a two-stage procedure. We report the case of a 21-year-old female myelomeningocele patient with end-stage renal insufficiency who was treated with ileocytstoplasty and living related renal transplantation at a single stage.

Median effect analysis of efficacy versus adverse effects of immunosuppressants.

Background: A rigorous model to describe concentration-effect relations-the median effect analysis-was applied to quantitate immunosuppressive versus adverse effects in human renal transplantation.

Methods: The median effect equation was used to analyze data collected from three clinical studies, including the two phase III blinded, placebo-controlled trials (n = 1295 patients) of sirolimus versus azathioprine or placebo treatment added to a cyclosporine (INN, ciclosporin)/prednisone regimen and a sirolimus/azathioprine/prednisone (in the absence of cyclosporine) phase II cohort (n = 41 patients).

Results: The clinical effects correlated with drug concentrations as expressed by the median effect equation.

Identification of a ligand-binding site in the Na+/bile acid cotransporting protein from rabbit ileum.

Reabsorption of bile acids occurs in the terminal ileum by a Na(+)-dependent transport system composed of several subunits of the ileal bile acid transporter (IBAT) and the ileal lipid-binding protein. To identify the bile acid-binding site of the transporter protein IBAT, ileal brush border membrane vesicles from rabbit ileum were photoaffinity labeled with a radioactive 7-azi-derivative of cholyltaurine followed by enrichment of IBAT protein by preparative SDS gel electrophoresis. Enzymatic fragmentation with chymotrypsin yielded IBAT peptide fragments in the molecular range of 20.

Acute dyspnoea resulting from pulmonary oedema as the first sign of a phaeochromocytoma.

The day after undergoing neck dissection, a 42-year-old woman developed acute dyspnoea due to pulmonary oedema. Measurements with a Swan-Ganz catheter revealed not only cardiac depression but also a greatly increased peripheral vascular resistance: 5,400 dyn x s x cm(-5)/m2. A phaeochromocytoma with acute cardiac failure leading to pulmonary oedema was considered.

Laparoscopic management of a paraesophageal hernia with intrathoracic stomach in infants.

Paraesophageal hernia type III in which the stomach lies in the thorax is a rare condition in children. Recently two children presented with a large type III paraesophageal hernia with an intrathoracic stomach. The stomach could be retrieved from the thorax laparoscopically and the procedure was completed with a Thai antireflux procedure.

Time-resolved spectroscopy of sulfur- and carboxy-substituted N-alkylphthalimides.

The photophysical and photochemical properties of N-phthaloyl-methionine (1), S-methyl-N-phthaloyl-cysteine methyl ester (2) and N-phthaloyltranexamic acid (3) were studied by time-resolved UV/Vis spectroscopy, using laser pulses at 248 or 308 nm. The quantum yield of fluorescence is low (phi(f)< 10(-2)) for 1-3 in fluid and glassy media, whereas that of phosphorescence is large (0.3-0.

Value of tumor M2 (Tu M2-PK) in patients with renal carcinoma.

Pyruvate kinase is one of the glycolytic key enzymes. It exists in various isoforms which are expressed in different cell types. One of these isoforms, the type Tu M2-PK, is strongly overexpressed by tumor cells and released into body fluids.

Bile acid-oligodeoxynucleotide conjugates: synthesis and liver excretion in rats.

The synthesis of bile acid oligodeoxynucleotide conjugates via the 3-OH group of the bile acids is described. When used in vivo in rats, covalent conjugation of an oligodeoxynucleotide via a linker to cholic acid resulted in an increased biliary excretion of bile acid-oligodeoxynucleotide conjugates compared to unconjugated oligodeoxynucleotides.

Photocyclization of 2-azabicyclo[3.3.0]octane-3-carboxylate derivatives: induced and noninduced diastereoselectivity.

[reaction: see text] The decarboxylative photocyclization of potassium 2-azabicyclo[3.3.0]octanoate ethylene-linked to phthalimide leads to a mixture of two diastereoisomeric products.

Diastereo- and Enantioselective Synthesis of Pyrrolo[1,4]benzodiazepines through Decarboxylative Photocyclization.

Memory of chirality in triplet 1,7-diradicals was detected for the first time and to a remarkably high degree in the decarboxylative photocyclization of the proline derivative of N-phthaloyl anthranilic acid 1 into 2 (X=H: 45 % yield, 86 % ee; X=Cl: 50 % yield, 79 % ee).

Identification of binding proteins for cholesterol absorption inhibitors as components of the intestinal cholesterol transporter.

To identify protein components of the intestinal cholesterol transporter, rabbit small intestinal brush border membrane vesicles were submitted to photoaffinity labeling using photoreactive derivatives of 2-azetidinone cholesterol absorption inhibitors. An integral membrane protein of M(r) 145.3+/-7.

Isolation of segments of homologous genes with only one conserved amino acid region via PCR.

We present a method which allows the isolation of fragments from genes coding for homologous proteins via PCR when only one block of conserved amino acids is available. Sets of degenerated primers are defined by reverse translation of the conserved amino acids such that each set contains not more than 128 different sequences. The second primer binding site is provided by a special cassette that is designed such that it does not allow binding of the second primer prior to being copied by DNA synthesis.

Identification of the bile acid-binding site of the ileal lipid-binding protein by photoaffinity labeling, matrix-assisted laser desorption ionization-mass spectrometry, and NMR structure.

The ileal lipid-binding protein (ILBP) is the only physiologically relevant bile acid-binding protein in the cytosol of ileocytes. To identify the bile acid-binding site(s) of ILBP, recombinant rabbit ILBP photolabeled with 3-azi- and 7-azi-derivatives of cholyltaurine was analyzed by a combination of enzymatic fragmentation, gel electrophoresis, and matrix-assisted laser desorption ionization (MALDI)-mass spectrometry. The attachment site of the 3-position of cholyltaurine was localized to the amino acid triplet His(100)-Thr(101)-Ser(102) using the photoreactive 3,3-azo-derivative of cholyltaurine.

Downregulation of ileal bile acid absorption in bile-duct-ligated rats.

Background/aims: Accumulation of toxic bile acids in cholestasis contributes to liver injury and depends on their synthesis, secretion and intestinal absorption. In the present study, we investigated the effect of cholestasis on the active ileal absorption of bile acids in vivo and the adaptation of transporters involved in ileal bile acid absorption.

Methods: Male Wistar rats underwent ligation of the common bile duct or biliary diversion.

MPH1, a yeast gene encoding a DEAH protein, plays a role in protection of the genome from spontaneous and chemically induced damage.

We have characterized the MPH1 gene from Saccharomyces cerevisiae. mph1 mutants display a spontaneous mutator phenotype. Homologs were found in archaea and in the EST libraries of Drosophila, mouse, and man.

Reduction-oxidation (redox) state regulation of matrix metalloproteinase activity in human fetal membranes.

Objective: The mechanisms underlying membrane rupture at term and preterm are obscure. Collagenolytic activity of matrix metalloproteinases in amniochorionic membranes increases during spontaneous term and preterm labor associated with intra-amniotic infection. We sought to test the hypothesis that reduction-oxidation homeostasis, which is altered in inflammatory states, directly regulates amniochorionic matrix metalloproteinases.

Ileal bile acid transport regulates bile acid pool, synthesis, and plasma cholesterol levels differently in cholesterol-fed rats and rabbits.

We investigated the effect of ileal bile acid transport on the regulation of classic and alternative bile acid synthesis in cholesterol-fed rats and rabbits. Bile acid pool sizes, fecal bile acid outputs (synthesis rates), and the activities of cholesterol 7alpha-hydroxylase (classic bile acid synthesis) and cholesterol 27-hydroxylase (alternative bile acid synthesis) were related to ileal bile acid transporter expression (ileal apical sodium-dependent bile acid transporter, ASBT). Plasma cholesterol levels rose 2.

Metabolic approaches for the optimisation of recombinant fermentation processes.

The aim of this work was the establishment of a novel method to determine the metabolic load on host-cell metabolism resulting from recombinant protein production in Escherichia coli. This tool can be used to develop strategies to optimise recombinant fermentation processes through adjustment of recombinant-protein expression to the biosynthetic capacity of the host-cell. The signal molecule of the stringent-response network, guanosine tetraphosphate (ppGpp), and its precursor nucleotides were selected for the estimation of the metabolic load relating to recombinant-protein production.

Functional analysis of 150 deletion mutants in Saccharomyces cerevisiae by a systematic approach.

In a systematic approach to the study of Saccharomyces cerevisiae genes of unknown function, 150 deletion mutants were constructed (1 double, 149 single mutants) and phenotypically analysed. Twenty percent of all genes examined were essential. The viable deletion mutants were subjected to 20 different test systems, ranging from high throughput to highly specific test systems.

Alterations of carbohydrate and lipid intermediary metabolism during inhibition of glucose-6-phosphatase in rats.

S 4048 (1-[2-(4-Chloro-phenyl)-cyclopropylmethoxy]-3, 4-dihydroxy-5-(3-imidazo[4, 5-b]pyridin-1-yl-3-phenyl-acryloyloxy)-cyclohexanecarboxylic acid), a derivative of chlorogenic acid, specifically inhibits the glucose-6-phosphate translocating component T1 of the glucose-6-phosphatase system. Its pharmacological effect was studied on carbohydrate and lipid parameters in rats. In starved and fed rats, S 4048 caused a dose-dependent reduction of blood glucose levels with a corresponding increase in hepatic and renal glycogen and glucose-6-phosphate.