[Treatment with recombinant interferon alfa-2a and pregnancy in a patient with chronic viral hepatitis C].
Explore the source record for details and available documents.
Adult↗
Biomedical subjects
H Michel
Publications and source records attributed to H Michel.
Heterologous expression of the human D2S dopamine receptor in protease-deficient Saccharomyces cerevisiae strains.
The cDNA for the human D2S dopamine receptor has been functionally expressed in the unicellular yeast Saccharomyces cerevisiae. The original D2S gene and an elongated D2S gene with an N-terminal fusion to the first 24 amino acids of the STE2 gene from S. cerevisiae were introduced into the episomal yeast expression vector YEp51 under the control of the GAL10 promoter. Expression studies performed in a wild-type strain and in two protease-deficient strains of S. cerevisiae revealed that the receptor was functionally expressed with respect to its ligand-binding properties. The KD values for the binding of the dopamine antagonist [3H]spiperone were calculated to be 1.6 nM for the D2S receptor alone and 1.9 nM for the STE2-D2S chimaera. Both membrane proteins could be further characterized by ligand-displacement studies using certain dopamine agonists and antagonists. D2S dopamine-receptor-specific polyclonal antibodies were used to monitor the heterologous expression of the receptor. Western-blot analysis of membranes prepared from transformed yeast cells producing either the receptor protein alone or the receptor fusion protein revealed apparent molecular masses of 40 kDa (D2S receptor alone) and 42 kDa (STE2/D2S receptor fusion protein). It could be shown that, in comparison to the expression in a wild-type S. cerevisiae strain, the amount of receptor degradation was drastically reduced in the protease-deficient strains. The localizations of the heterologously produced dopamine receptor and of the chimaera in the recombinant yeast were studied by immunogold electron microscopy and were found to be restricted mainly to the vacuole of the cells.
Base Sequence↗
Structure of the photosynthetic reaction centre from Rhodobacter sphaeroides at 2.65 A resolution: cofactors and protein-cofactor interactions.
BACKGROUND: Photosynthetic reaction centres (RCs) catalyze light-driven electron, transport across photosynthetic membranes. The photosynthetic bacterium Rhodobacter, sphaeroides is often used for studies of RCs, and three groups have determined the structure of its reaction centre. There are discrepancies between these structures, however, and to resolve these we have determined the structure to higher resolution than before, using a new crystal form. RESULTS: The new structure provides a more detailed description of the Rb. sphaeroides RC, and allows us to compare it with the structure of the RC from Rhodopseudomonas viridis. We find no evidence to support most of the published differences in cofactor binding between the RCs from Rps. viridis and Rb. sphaeroides. Generally, the mode of cofactor binding is conserved, particularly along the electron transfer pathway. Substantial differences are only found at ring V of one bacteriochlorophyll of the 'special pair' and for the secondary quinone, QB. A water chain with a length of about 23 A including 14 water molecules extends from the QB to the cytoplasmic side of the RC. CONCLUSIONS: The cofactor arrangement and the mode of binding to the protein seem to be very similar among the non-sulphur bacterial photosynthetic RCs. The functional role of the displaced QB molecule, which might be present as quinol, rather than quinone, is not yet clear. The newly discovered water chain to the QB binding site suggests a pathway for the protonation of the secondary quinone QB.
Bacteriochlorophylls↗
Structural and functional consequences of a Glu L212-->Lys mutation in the QB binding site of the photosynthetic reaction center of Rhodopseudomonas viridis.
The properties of the quinone acceptor complex in the photosynthetic reaction center of the atrazine-resistant Rhodopseudomonas viridis mutant A2 (Glu L212-->Lys) were studied by EPR spectroscopy and by photoelectric measurements. The EPR signal attributed to the semiquinone-iron (QB-Fe2+) was significantly different from wild type and resembled that found in PS II. Essentially normal oscillations of QB-Fe2+ were observed upon flash illumination. The kinetics of the first and the second electron transfer from QA to QB were characterized by a photoelectric double-flash method. Compared to wild type, the rate of the first electron transfer in the large majority of reaction centers was decreased drastically from k1 = (18 microseconds)-1 in the wild type to (70 ms)-1 in the mutant, whereas the second electron transfer was only slightly slowed down with a rate of k2 = (260 microseconds)-1 compared to (65 microseconds)-1 in wild type (pH 7). When the pH was raised above 10, in a major fraction of the reaction centers a fast kinetics of the first electron transfer, like that in wild type, reappeared. The experimental results are interpreted as an effect of the positive charge on the lysine causing a significant structural change of the QB binding pocket and a strongly diminished affinity for ubiquinone. The slow QA(-)-->QB electron transfer kinetics are thus attributed to ubiquinone binding, which is rate limiting. The possible role of the residue Glu L212, which is conserved in all purple bacteria, in electron and proton transfer to QB is discussed.
Atrazine↗
Constitutive expression of the human D2S-dopamine receptor in the unicellular yeast Saccharomyces cerevisiae.
The cDNA for the human D2S-dopamine receptor has been functionally expressed in the unicellular yeast Saccharomyces cerevisiae. Two expression plasmids pRS421D2 (original D2S-gene coding region) and pRS421D2S (the first 24 aa of the yeast STE2-gene are fused to the N-terminus of the D2S-gene) were constructed and transformed into the protease deficient S. cerevisiae strain cI3-ABYS-86. Northern blot analysis of total RNA from transformed yeast clones revealed that for both constructs the D2S-gene was constitutively transcribed from the plasmids PMA1 promoter. Membranes prepared from recombinant S. cerevisiae exhibited saturable binding with the antagonist [3H]methylspiperone. Competition studies revealed pharmacological properties for these sites which were comparable to those reported for the D2-receptor heterologously expressed in mammalian cells. The expression of the receptor was monitored by Western blot analysis using an antiserum raised against a peptide from the third intracellular domain of the receptor protein and by ligand binding assay.
Amino Acid Sequence↗
Expression of the human D2S dopamine receptor in the yeasts Saccharomyces cerevisiae and Schizosaccharomyces pombe: a comparative study.
The yeasts Saccharomyces cerevisiae and Schizosaccharomyces pombe were tested for heterologous expression of the human D2S dopamine receptor. The cDNA coding for the dopamine receptor was cloned into high copy number plasmids with inducible promoters. After transformation into the yeasts recombinant clones were examined for the presence of functional receptor by radioligand binding using the antagonist [3H]spiperone. Subsequent Western blot analysis of positive recombinants with an antiserum raised against a peptide from the third intracellular domain of the receptor protein revealed the production of a protein with an apparent molecular mass of 40 kDa in both yeasts. Membranes harvested from recombinant yeast clones exhibited saturable binding of the dopaminergic antagonist [3H]spiperone with Kd values of 1.3 nM in S. cerevisiae and 0.25 nM in S. pombe. The rank order of potencies for several dopaminergic ligands to displace specific [3H]spiperone binding to membranes were the same in both yeasts, whereas the affinities for ligands differed significantly.
Binding Sites↗
Definition of specific peptide motifs for four major HLA-A alleles.
Allele-specific motifs for the human MHC class I molecules, HLA-A1, A3, A11, and A24 were characterized by three complementary approaches. First, amino acid sequence analysis of acid eluted peptide pools from affinity purified class I molecules defined putative motifs 9 or 10 amino acids in length and bearing critical anchor residues at position 2 and at the COOH-terminal. These motifs were distinct, with the exception of the HLA-A3 and A11 motifs that were very similar to each other. Second, the correctness of these putative motifs was verified by analyzing the binding capacity of polyalanine peptide analogues to purified HLA-A molecules. Several alternative anchor residues that were not obvious from the pooled peptide sequencing analysis were identified. Third, sequences of individual peptides eluted from HLA-A1, A11, and A24 were determined by tandem mass spectrometry. Nonamers were the predominant species, although peptides of 8, 10, 11, and 12 amino acids in length were also identified. These peptides displayed anchor residues predicted by the specific motifs at position 2 and at the COOH-terminal, regardless of peptide length. Synthetic versions of the naturally processed peptides were shown to bind to the appropriate HLA-A alleles with IC50 values in the 0.3- to 200-nM range. A rational approach to search Ags with known amino acid sequences for epitopes restricted by some of the most common HLA-A types and of potential clinical importance is now feasible.
Alleles↗
[Hepato-digestive disorders in athletic practice].
Gastrointestinal and liver disorders are often observed in high performance athletes, especially those training for the increasingly popular endurance sports including the marathon and the triathlon. The disorders often start with stress before competition or training, followed by dehydration during the event. Insufficient training is an aggravating factor as are certain environmental factors including hot climate, irregular terrain and high altitude. Athletes may also consume non-steroid anti-inflammatory drugs, for example after a minor bone lesion or joint sprain, in an attempt to maintain their highest level of performance. Gastric signs include epigastric pain known to be caused by ischaemic gastritis resulting from decreased splanchnic flow and increased vasoconstriction in the gastric mucosa. Gastrooesophageal reflux results from modifications in sphincter tone and gastric emptying. Drinking hyperosmolar liquids also plays a role. Abdominal pain, diarrhoea, melena and uncommonly ischaemic colitis are the main signs of colic disorders. Mesenteric ischaemia may occur due to lowered splanchnic blood supply (by as much as 80% in some cases). Mechanical trauma is another mechanism; in marathon runners the "caecal slap syndrome" is a repeated microtrauma of the caecum against a hypertrophied muscular wall. Waterborne infectious agents may also lead to colic lesions. Exertion heat stroke is an emergency situation which can cause multiple organ damage and usually occurs after long intense exercise, often, but not always in a hot environment. Uncompensated thermogenesis and excessive loss of water by perspiration leads to central hyperthermia and ischaemic hepatic necrosis. Fatal liver failure has been observed. More or less severe symptoms of gastrointestinal or hepatic disorders are observed in 30% of high performance athletes and the incidence may reach 40% in those who have trained insufficiently. Such disorders lead to reduced performance in 10% of these athletes.
Colonic Diseases↗
Von Willebrand's disease, digestive angiodysplasia, and estrogen-progesterone treatment.
Explore the source record for details and available documents.
Angiodysplasia↗
Structure and function of the photosynthetic reaction center from Rhodobacter sphaeroides.
The three-dimensional structure of the photosynthetic reaction center from Rhodobacter sphaeroides is described. The reaction center is a transmembrane protein that converts light into chemical energy. The protein has three subunits: L, M, and H. The mostly helical L and M subunits provide the scaffolding and the finely tuned environment in which the chromophores carry out electron transfer. The details of the protein-chromophore interactions are from studies of a trigonal crystal form that diffracted to 2.65-A resolution. Functional studies of the multi-subunit complex by site-specific replacement of key amino acid residues are summarized in the context of the molecular structure.
Crystallography, X-Ray↗
Purification and characterization of a high-molecular-weight form of recombinant human interleukin-2.
During purification of recombinant Interleukin-2 (rIL-2) by reversed-phase HPLC, early fractions are discarded due to the presence of an unidentified form of rIL-2. A procedure has been developed to isolate and purify this unidentified form of rIL-2. The purification process involves two chromatography steps and utilizes a Bakerbond Carboxy-Sulfon (CS) column under two different conditions. This material, designated as a high-molecular-weight form of rIL-2 (HMWrIL-2), exhibits lower mobility during SDS-PAGE and has a pI which is approximately one unit less than that of rIL-2, but has similar bioactivity to rIL-2. Structural analysis through enzymatic cleavage, HPLC peptide mapping, mass spectrometry, sequencing, and amino acid composition revealed that the difference between these two proteins is a C-terminal extension of 11 amino acids. This extension could be the result of a nonstandard translation event.
Amino Acid Sequence↗
Tianeptine--an instance of drug-induced hepatotoxicity predicted by prospective experimental studies.
We report the case of a patient who developed acute hepatitis after taking tianeptine, a new tricyclic antidepressant, for 8 weeks. Hepatitis exhibited cholangitis-like clinical features and was associated with hypersensitivity manifestations suggestive of an immuno-allergic mechanism. Histological examination showed microvesicular steatosis. The discontinuation of tianeptine administration was followed by complete recovery. Immunoallergic hepatitis and microvesicular steatosis were predicted 2 years ago from prospective experimental studies prompted by the similarity of the chemical structures of tianeptine and amineptine, another tricyclic antidepressant, well-known for its hepatotoxicity. Experimentally, tianeptine has been found to be oxidized into reactive metabolites in several rodents and human liver and to produce microvesicular steatosis probably through inhibition of mitochondrial beta-oxidation of fatty acid in mice. This case illustrates the value of prospectively assessing potential hepatotoxicity mechanisms for new compounds chemically related to drugs already known to be hepatotoxic.
Antidepressive Agents, Tricyclic↗
Octreotide therapy of large-volume refractory AIDS-associated diarrhea: a randomized controlled trial.
OBJECTIVE: To compare the effect of octreotide (a long-acting somatostatin analog) to that of antidiarrheal therapy plus placebo on large-volume refractory AIDS-associated diarrhea. DESIGN: A randomized controlled trial. SETTING: Referral-based clinic and hospital in a tertiary care center. PATIENTS: Twenty male patients with AIDS and refractory diarrhea, with stool volume > 1000 ml/day who failed to improve after initial supportive management. All patients finished the study. INTERVENTIONS: Patients were randomly given either octreotide in doses of 100, 200 and 300 micrograms subcutaneously every 8 h, or high doses of loperamide and diphenoxylate orally plus placebo subcutaneously for 10 days. MAIN OUTCOME MEASURES: Bowel movements and stool volume were registered before and every day after treatment by the patients themselves and the nursing personnel. RESULTS: Patients from both groups were similar for age, time of AIDS diagnosis, duration of diarrhea and etiology. Baseline mean bowel movements per day (9.4 +/- 2.8 in the octreotide group versus 10 +/- 3.1 in controls) and baseline mean stool volume (2753 +/- 840 versus 2630 +/- 630 ml/day, respectively) were similar in both groups before therapy (P < 0.05). Mean bowel movements per day after 10 days of therapy was 2.1 +/- 1.6 in the octreotide group versus 7 +/- 3 in controls (P < 0.05). Mean stool volume after 10 days of therapy was 485 +/- 480 in the octreotide group versus 1080 +/- 420 ml/day in controls (P < 0.05). Complete response (stool volume < 250 ml/day) was observed in two patients from the octreotide group and none from controls; partial response (decrease > 50% in stool volume) in four and two; and no response (decrease < 50% or no change) in four and eight (P < 0.05), respectively. Side-effects occurred in eight out of 10 octreotide patients and three out of 10 controls (P < 0.05), but none were significant to result in discontinuation of medication. CONCLUSION: Octreotide proved to be superior to conventional therapy in this short-term treatment of large-volume refractory AIDS-associated diarrhea.
Acquired Immunodeficiency Syndrome↗
Protein diets and the cirrhotic patient.
Explore the source record for details and available documents.
Dietary Proteins↗
[Palliative endoscopic treatment of adenocarcinoma of Vater's ampulla: medium and long-term results].
The palliative endoscopic treatment of tumors of the ampulla of Vater provides good short-term symptomatic results, while long-term results remain unknown. This study to assessed the course of 17 patients with carcinoma of the ampulla of Vater treated palliatively by endoscopy and monitored for a 5-year-period. From january 1985 to december 1989, 35 patients were diagnosed as having carcinoma of the ampulla of Vater. For 18 of them, curative surgery was performed, while for the 17 remaining 17 patients, palliative endoscopic treatment was proposed because of metastatic extension or surgical risk. Endoscopic treatment always included endoscopic sphincterotomy, and, in some cases, insertion of a biliary endoprosthesis. All patients were monitored until death or the end of follow-up on September 30, 1990. Endoscopic sphincterotomy was performed in 13 of the 17 patients, either alone in 10 cases, or with prosthesis in the other 3 cases. For the 4 other patients, endoscopic sphincterotomy could not be performed (large tumor in 2 cases, presence of duodenal diverticulum in 2 other cases). The 13 patients who underwent endoscopic treatment experienced rapid symptomatic improvement. Jaundice and cholangitis consistently recurred within a period of 1 to 44 weeks regardless of initial treatment. All recurrences except one, were successfully retreated by endoscopy (enlargement of initial sphincterotomy in 6 cases, insertion or replacement of prosthesis in 12 cases).(ABSTRACT TRUNCATED AT 250 WORDS)
Adenocarcinoma↗
[Lactulose-neomycin combination versus placebo in the treatment of acute hepatic encephalopathy. Results of a randomized controlled trial].
OBJECTIVES: The effectiveness of the association of lactulose with neomycin in the treatment of acute hepatic encephalopathy has never been assessed. The aim of this study was to compare the effects of lactulose-neomycin combination versus placebo in acute hepatic encephalopathy. METHODS: Eighty patients with cirrhosis were randomly treated for 5 days with placebo (n = 40) or with lactulose-neomycin (n = 40). Both groups were similar for all variables. RESULTS: The course of encephalopathy was similar in both groups. In the lactulose-neomycin group: 26 PATIENTS recovered, 3 remained unchanged, 3 worsened, 6 died, 2 were lost to follow-up. In the placebo group: 28 recovered, 2 remained unchanged, 2 worsened, 6 died, one was lost the follow-up, one dropped out of the study. Lactulose-neomycin treatment was not well tolerated in a significant number of patients. CONCLUSION: Lactulose-neomycin combination should not be used in the treatment of acute hepatic encephalopathy.
Acute Disease↗
[Acute hepatitis caused by Listeria monocytogenes infection].
We report the case of a 40 year-old woman, pregnant for 4 months, with acute hepatitis revealed by jaundice, fever and high serum aminotransferase levels. Infection by Listeria monocytogenes was demonstrated by blood cultures. The course of the disease was characterized by abortion and complete recovery of hepatitis within 4 weeks after antibiotic administration. This report shows that listeriosis can cause acute severe hepatitis.
Abortion, Spontaneous↗
Pharmacokinetics of the organic nitrates trans-N-(4-nitroxycyclohexyl)-urea in dogs and trans-N-(4-nitroxycyclohexyl)-acetamide in dogs and in man.
The pharmacokinetic behavior of the organic nitrates BM 12.1247 (trans-N-(4-nitroxycyclohexyl)-urea) and BM 12.1307 (trans-N-(4-nitroxycyclohexyl)-acetamide, CAS 137291-91-3) were examined in beagle dogs after oral and intravenous administration. To this end, a reliable and specific assay using capillary gaschromatography with electron capture detection (GC-ECD) was developed. BM 12.1247 showed its maximum plasma level after 2.2 h by oral application; the bioavailability was nearly 100%. The elimination half-life of 8.8 h p.o. Corresponded to the half-life after i.v. administration, concerning BM 12.1307, the elimination half-lives were still longer, they reached 11-13 h and bioavailability reached 68-70%; these results were confirmed by crossover tests. In a first application of healthy volunteers it was possible to show that the organic nitrate BM 12.1307 is eliminated much more slowly in man than in dog, the half-life of the compound in man being longer than the half-life in dog by a factor of 2.3.
Acetamides↗