Search PubMed⌕ Search

Biomedical subjects

J Albrecht

Publications and source records attributed to J Albrecht.

At least 127 records · Page 7Linked to original sources
PubMed1990

A randomized, controlled trial of interferon alfa-2b alone and after prednisone withdrawal for the treatment of chronic hepatitis B. The Hepatitis Interventional Therapy Group.

BACKGROUND AND METHODS: Chronic hepatitis B is a common and often progressive liver disorder for which there is no accepted therapy. To assess the efficacy of treatment with interferon, we randomly assigned patients with chronic hepatitis B to one of the following regimens: prednisone for 6 weeks followed by 5 million units of recombinant interferon alfa-2b daily for 16 weeks; placebo followed by 5 million units of interferon daily for 16 weeks; placebo followed by 1 million units of interferon daily for 16 weeks; or observation with no treatment. RESULTS: Hepatitis B e antigen and hepatitis B viral DNA disappeared from serum significantly more often in the patients given prednisone plus interferon (16 of 44 patients, or 36 percent) or 5 million units of interferon alone (15 of 41; 37 percent) than in the untreated controls (3 of 43; 7 percent; P less than 0.001); the difference between those given 1 million units of interferon (7 of 41; 17 percent) and the controls was not significant. The strongest independent predictor of a response to treatment was the amount of hepatitis B viral DNA in serum at entry (P less than 0.0001). Of the 38 patients who responded to interferon, 33 (87 percent) had normal serum aminotransferase levels after therapy; 11 patients who responded (29 percent), but no controls, lost the hepatitis B surface antigen. Blinded histologic assessment revealed a significant improvement in periportal necrosis in the treated patients (P = 0.03). CONCLUSIONS: In chronic hepatitis B, treatment with interferon alfa-2b (5 million units per day for 16 weeks) was effective in inducing a sustained loss of viral replication and achieving remission, assessed biochemically and histologically, in over a third of patients. Moreover, in about 10 percent of the patients treated with interferon, hepatitis B surface antigen disappeared from serum.

Adult↗
PubMed1990

L-methionine-DL-sulfoximine induces massive efflux of glutamine from cortical astrocytes in primary culture.

L-Methionine-DL-sulfoximine (MSO) is a potent convulsant which metabolically and morphologically primarily affects astroglia, and the links between the gliotoxic and neurophysiological effects of MSO are not clear. A 5 min treatment with 3 mM MSO increased the rate of efflux of newly loaded radiolabelled glutamine (Gln) from rat cortical astrocytes in primary culture to more than 400% of the basal efflux. MSO did not affect the efflux of the neurotransmitter amino acids GABA or D-aspartate (a non-metabolizable analogue of L-glutamate), under the same experimental conditions. MSO-induced overflow with Gln, which according to a recent account strongly interacts with the N-methyl-D-aspartate (NMDA) receptor complex, may contribute to the convulsive action of the drug.

Animals↗
PubMed1990

Acute hepatic encephalopathy decreases potassium-evoked calcium uptake in astrocytes but not in synaptosomes of the rat.

45CaCl2 uptake at low (5 mM), and high, depolarizing (65 mM) KCl concentration was measured in a fraction enriched in astrocytes, a crude mitochondrial-synaptosomal (P2) preparation and in purified synaptosomes derived from normal rats and from rats with thioacetamide-induced acute hepatic encephalopathy (HE). HE was found to reduce the potassium-evoked component of the astroglial uptake to 50% of its control level, without affecting the uptake into the P2 fraction or synaptosomes. The results are in keeping with the view that astrocytes are the cells whose metabolism and functions are predominantly affected during HE.

Acute Disease↗
PubMed1990

Activation of arginine metabolism to glutamate in rat brain synaptosomes in thioacetamide-induced hepatic encephalopathy: an adaptative response?

Crude (P2) synaptosomes derived from rats with acute hepatic encephalopathy (HE) induced with thioacetamide showed a slightly increased uptake of radiolabeled arginine (ARG) and a 2.5-fold enhanced conversion of newly taken-up ARG to both glutamate (GLU) and gamma-aminobutyric acid (GABA) as compared with control synaptosomes. Pulse treatment of the preloaded synaptosomes with a high potassium medium decreased their radioactive GLU and GABA content without affecting the content of the precursor ARG. This result, which was identical with control or HE preparations, appears to indicate that ARG contributes at least, in part, to the synthesis of neurotransmitter GLU or GABA. As measured in purified synaptosomal preparations, HE increased by about 50% the activities of arginase and ornithine-delta-aminotransferase--the two enzymes of the ARG to GLU shunt. It is postulated that increased conversion of ARG to GLU may compensate for excessive utilization of the latter amino acid as an ammonia trap during HE and, as such, may be considered as an adaptative response of the synaptic compartment to this pathological condition.

Acetamides↗
PubMed1989

Rapid decrease of high affinity ouabain binding sites in hippocampal CA1 region following short-term global cerebral ischemia in rat.

High affinity [3H]ouabain binding was examined in the hippocampal CA1 region and frontal cortex of rats subjected to 5 min complete cerebral ischemia in a clinical death model, and to subsequent resuscitation. A decrease of Bmax directly after ischemia and its further gradual decrease during 120 min of reperfusion were noted in the ischemia-vulnerable CA1 region, whereas no change of Bmax was observed in frontal cortex. The apparent Kd constant showed insignificant fluctuations in either of the two brain regions. Since ouabain binds with high affinity to the neuronal (alpha +)-form of Na+/K+-ATPase, the results indicate a rapid enzyme loss in CA1 neurons. The high affinity ouabain binding test proved to be a sensitive detector of premorphological changes in nerve cell membranes in ischemia.

Animals↗
PubMed1989

L-glutamate stimulates the efflux of newly taken up glutamine from astroglia but not from synaptosomes of the rat.

Bulk isolated rat astrocytes loaded with [14C] glutamine (Gln) were superfused on glass fiber filters with a standard Krebs-Henseleit medium until the basal efflux of the radioactivity became constant. The samples were then pulse-treated with: L-glutamate (Glu), gamma-aminobutyric acid (GABA), L-aspartate (Asp), cold Gln, or catecholamines, each at 0.5 mM concentration. Of the neurotransmitters tested, only Glu stimulated the efflux of radio-labelled Gln. The effect of Glu was sodium-dependent and was not mimicked by the Glu-receptor agonists: N-methyl-D-aspartate (NMDA), quisqualate (Quis) or kainate (KA), indicating a transport-mediated mechanism. Glu did not stimulate the efflux of newly taken up glutamine from either crude or purified brain synaptosomes, which is in keeping with the existing evidence that astrocytes function as a glutamine donor to other compartments of the central nervous system.

Animals↗
PubMed1988

Changes in the activity of gamma-glutamyl transpeptidase in brain microvessels, astroglial cells and synaptosomes derived from rats with hepatic encephalopathy.

Prolonged thioacetamide treatment increased gamma-glutamyl transpeptidase (GGT) activity in the rat liver and induced neurological symptoms of hepatic encephalopathy (HE). The enzyme activity measured without an amino acid or peptide acceptor was increased in cortical capillaries and synaptosomes, but remained unchanged in astroglia isolated from the brains of hyperammonemic rats. In the presence of L-glutamine the activity of GGT was stimulated by about 60% in astroglial cells while in the capillaries and synaptosomes the amino acid stimulation was less pronounced. Glycylglycine also stimulated the GGT activity in the astroglia more (4-fold) than in cortical capillaries or synaptosomes (3-fold). Similar stimulatory effects of these gamma-glutamyl moiety acceptors on the GGT activity were observed in capillaries, glial cells and synaptosomes derived from the brains of rats with HE. These results indicate that GGT may be involved in the excessive accumulation of large neutral amino acids (and some peptides) in the brain of rats with HE.

Animals↗
PubMed1988

Abundant 5 kb RNA of human cytomegalovirus without a major translational reading frame.

Although all herpesviruses are similar in their temporal regulation of gene expression, the organization of the immediate early (IE) genes varies markedly between the different members of the group. Most of the IE transcripts of human cytomegalovirus originate from a restricted region within the long unique segment of its linear dsDNA genome of 235 kb. One of the predominant transcripts from the IE region is a 5 kb RNA. Northern blot analyses revealed that this class of RNA is continuously present in infected cells. It was detected at high levels in IE and late RNA preparations, and in low amounts in early RNA preparations. It was not confined to the poly(A)+ fraction upon oligo(dT) selection, but also appeared in similar amounts in poly(A)- fractions. Fine mapping of this transcript was done by nuclease protection and primer extension. The RNA appeared to be unspliced, and no signals such as TATA or CCAAT, known to be important elements in eukaryotic RNA polymerase II promoters, were found close to the 5' end. Sequence analysis revealed multiple stop codons throughout the AT-rich potential coding region. Since no splicing was found to occur, the largest protein deduced from the DNA sequence would be of not more than 12,000 Mr. However, a computer program designed to detect protein-coding DNA sequences by codon usage did not reveal significant evidence for a protein encoded in this region. Therefore this RNA is likely to represent an unprecedented case of a large non-coding transcript present in cells that are lytically infected by an animal virus.

Base Sequence↗
PubMed1987

Is neurotransmitter histamine predominantly inactivated in astrocytes?

Rat synaptosomes and astroglia cell-enriched fraction were tested for the uptake of histamine (HA) and its precursor histidine, and the activities of the HA-synthesizing enzyme, histidine decarboxylase (HD) and HA-metabolizing enzyme, histamine methyltransferase (HMT). While histidine uptake was more active into synaptosomes than into astrocytes, only astrocytes were capable of a significant HA uptake. Kinetic analysis of the astrocytic HA uptake revealed a high affinity-low capacity system (Km = 5 X 10(-7) M, Vmax = 1.6 X 10(-12) mol.min-1 X mg-1) similar to the astroglial transport systems for other neurotransmitters. HMT was 70% more active in astrocytes than in synaptosomes, whereas HD activity was not different in these two preparations. The results indicate that astrocytes could be the major site of neurotransmitter HA inactivation.

Animals↗
PubMed1987

Cerebral oxygen consumption in experimental hepatic encephalopathy: different responses in astrocytes, neurons, and synaptosomes.

Oxygen consumption was measured polarographically in fractions enriched in astrocytes or neurons, and in synaptosomes derived from rats in which two subsequent stages of acute hepatic encephalopathy were induced by thioacetamide treatment. A 30% decrease of oxygen consumption was noted in astrocytes from animals with coma, well in agreement with the decrease of whole cerebral oxygen consumption and the increase of whole brain ammonia. In contrast, at the same stage the oxygen consumption in neurons was increased by some 35%, whereas synaptosomes remained unaffected. The results are in keeping with the view that astrocytes are the cells whose metabolism is primarily affected during hepatic encephalopathy. On the other hand, they support recent pathophysiologic evidence that ammonia-induced neuronal dysfunction is not a consequence of impaired energy metabolism in the nerve cells.

Animals↗
PubMed1987

Enhanced potassium-stimulated gamma-aminobutyric acid release by astrocytes derived from rats with early hepatogenic encephalopathy.

Bulk-isolated astrocytes from rats with early hepatogenic encephalopathy (HE) induced with thioacetamide responded to the increase of potassium in the incubation medium from 5 mM to 75 mM with a markedly enhanced release of previously taken up [14C]gamma-aminobutyric acid ([14C]GABA). The process was not affected by omission of calcium and/or addition of EGTA to the incubation medium. Only a slight stimulation of GABA release by high potassium was observed in astrocytes from control rats. In contrast, histamine and histidine were vigorously released from control astrocytes in high-potassium medium, and their release was not enhanced by HE, indicating that the observed phenomenon is specific for GABA.

Animals↗
PubMed1987

Primary structure and transcription of the genes coding for the two virion phosphoproteins pp65 and pp71 of human cytomegalovirus.

Human cytomegalovirus contains a phosphorylated matrix protein of 65,000 apparent molecular weight (65K phosphoprotein; pp65) and a related phosphoprotein of 71,000 molecular weight (pp71). The 65K phosphoprotein is usually by far the most abundant structural component found in culture-grown purified virus particles. This study describes the precise mapping of the genes for both polypeptides, giving the entire nucleotide sequences and the exact positions of the respective transcripts. The 65K phosphoprotein is coded for by the 5'-terminal part of an abundant 4-kilobase (kb) mRNA. The 71K phosphoprotein corresponds to the single translational reading frame of a rare nonspliced 1.9-kb mRNA that is coterminal with the 4-kb transcript. The promoter for 4-kb mRNA appears to be unusual in structure; it does not contain a characteristic TATA sequence. The expression of antigenic epitopes from pp65 may allow improved serodiagnosis of human cytomegalovirus infections.

Amino Acid Sequence↗