Biomedical subjects

H Michel

Publications and source records attributed to H Michel.

At least 19 recordsLinked to original sources

PubMed1992

Invariant chain peptides in most HLA-DR molecules of an antigen-processing mutant.

Class II major histocompatibility complexes bind peptides in an endosome-like compartment. When the class II null cell line 721.174 was transfected with class II DR3 genes, DR molecules were produced in normal amounts. However, the DR molecules were abnormally conformed and unstable because deletion of an antigen-processing gene had impaired intracellular formation of most class II-peptide complexes. Yet, 70 percent of the DR molecules still bore peptides, 80 percent of which were 21- to 24-amino acid fragments of the class II-associated invariant chain. These peptides were rare on DR3 from control cells. Thus, a defect in the main antigen-processing pathway revealed a process in which DR molecules bind long peptides derived from proteins present in the same compartment.

Amino Acid Sequence↗

PubMed1992

Renaturation and partial peptide sequencing of mitogen-activated protein kinase (MAP kinase) activator from rabbit skeletal muscle.

Mitogen-activated protein kinase (MAP kinase) activator was purified 2000-fold from skeletal muscle, and proteins which co-purified with the activator were analysed after SDS/PAGE by renaturation and partial sequencing. Activity for tyrosine and threonine phosphorylation of MAP kinase was present in two bands of approx. 48 and 46 kDa, which have sequence similarity to small GTP-binding protein p25 GDP dissociation inhibitor and protein kinases (PBS2, SPK1+, STE7, BYR1) respectively.

Amino Acid Sequence↗

PubMed1992

Hepatitis after germander (Teucrium chamaedrys) administration: another instance of herbal medicine hepatotoxicity.

OBJECTIVE: To show that germander (Teucrium chamaedrys), an herbal medicine used to facilitate weight loss, may be hepatotoxic and to delineate the nature of the injury. DESIGN: Retrospective study. SETTING: Liver units of several centers in the French Network of Pharmacovigilance. PATIENTS: Seven patients who developed hepatitis after germander administration and who had no other cause of liver injury. MEASUREMENTS: Clinical examination, liver function tests, various serologic tests, ultrasonography, and histologic study. RESULTS: Hepatitis characterized by jaundice and a marked increase in serum aminotransferase levels occurred 3 to 18 weeks after germander administration. Liver biopsy specimens in three patients showed hepatocyte necrosis. After discontinuing treatment with germander, jaundice disappeared within 8 weeks and recovery was complete in 1.5 to 6 months. In three cases, germander readministration was followed by the prompt recurrence of hepatitis. CONCLUSION: Germander may be hepatotoxic, which supports the view that herbal medicines are not always as safe as generally assumed.

Acute Disease↗

PubMed1992

Identification of Tyr-185 as the site of tyrosine autophosphorylation of recombinant mitogen-activated protein kinase p42mapk.

Tyrosine phosphorylation of 42-kDa mitogen-activated protein kinase (p42mapk) occurs during expression of the recombinant protein in Escherichia coli, as well as during in vitro phosphorylation of the protein purified from this source. Structural analyses were performed to identify the site(s) of tyrosine phosphorylation of recombinant p42mapk, both during expression of the protein in E. coli and during in vitro incubations with ATP/Mg2+/Mn2+. Mass spectrometry and phosphopeptide mapping showed that tyrosine phosphorylation of recombinant p42mapk occurs on Tyr-185, the site of regulatory tyrosine phosphorylation that occurs in mitogen-stimulated mammalian cells.

Amino Acid Sequence↗

PubMed1992

Peptides presented to the immune system by the murine class II major histocompatibility complex molecule I-Ad.

Between 650 and 2000 different peptides are associated with the major histocompatibility complex class II molecule I-Ad. Sequences for nine of these were obtained by a combination of automated Edman degradation and tandem mass spectrometry. All of the peptides are derived from secretory or integral membrane proteins that are synthesized by the antigen-presenting cell itself. Peptides were 16 to 18 residues long, had ragged NH2-and COOH-termini, and contained a six-residue binding motif that was variably placed within the peptide chain. Binding data on truncated peptides suggest that the peptide binding groove on class II molecules can be open at both ends.

Amino Acid Sequence↗

PubMed1992

Characterization of an improved reaction center preparation from the photosynthetic green sulfur bacterium Chlorobium containing the FeS centers FA and FB and a bound cytochrome subunit.

A photosynthetic reaction center complex was prepared from the green sulfur bacterium Chlorobium by solubilization of chlorosome-depleted membranes with lauryl maltoside, followed by anion-exchange chromatography and molecular sieve chromatography. The purified complex was characterized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, optical spectroscopy, and EPR spectroscopy. The major bands migrated at apparent molecular masses of 50, 42, and 32 kDa (heme-staining) and additional weaker bands at 22, 15, and 12 kDa. The isolated reaction center complex contained about 40 bacteriochlorophyll alpha molecules per primary electron donor, P840, assayed by photooxidation. It was competent in stable low-temperature photoreduction of the FeS centers FA and FB. The spectra of these acceptors and their low-temperature photochemistry in the purified complex were the same as found in intact Chlorobium membranes and similar to what had been described for photosystem I from plants. Membrane-bound cytochrome c553 copurified with the reaction center complex. A ratio of about four hemes per P840 was determined. This result indicates that cytochrome c553 that is closely associated with the reaction center is a tetraheme cytochrome, as described for some purple bacteria.

Bacteriochlorophylls↗

PubMed1992

Characterization of peptides bound to the class I MHC molecule HLA-A2.1 by mass spectrometry.

Antigens recognized by T cells are expressed as peptides bound to major histocompatibility complex (MHC) molecules. Microcapillary high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry was used to fractionate and sequence subpicomolar amounts of peptides isolated from the MHC molecule HLA-A2.1. Of 200 different species quantitated, eight were sequenced and four were found in cellular proteins. All were nine residues long and shared a distinct structural motif. The sensitivity and speed of this approach should enhance the analysis of peptides from small quantities of virally infected and transformed cells as well as those associated with autoimmune disease states.

Amino Acid Sequence↗

PubMed1992

HLA-A2.1-associated peptides from a mutant cell line: a second pathway of antigen presentation.

Peptides extracted from HLA-A2.1 class I major histocompatibility complex (MHC) molecules expressed on the antigen processing mutant CEMx721.174.T2 were characterized by electrospray ionization-tandem mass spectrometry. Only seven dominant peptides were found, in contrast to over 200 associated with HLA-A2.1 on normal cells. These peptides were derived from the signal peptide domains of normal cellular proteins, were usually larger than nine residues, and were also associated with HLA-A2.1 in normal cells. These results suggest that proteolysis of signal peptide domains in the endoplasmic reticulum is a second mechanism for processing and presentation of peptides for association with class I molecules.

Amino Acid Sequence↗

PubMed1992

Light-induced charge separation in Rhodopseudomonas viridis reaction centers monitored by Fourier-transform infrared difference spectroscopy: the quinone vibrations.

Static FTIR light-induced difference spectra have been recorded for reaction centers from Rhodopseudomonas viridis in the following charge-separated states: P+QA(-)-PQA, P+QB(-)-PQB, I(-)-I, I-QA(-)-IQA, and I-QA(2-)-IQA. A comparison of the I(-)-I difference spectra with the I-QA(-)-IQA difference spectra reveals new bands which can be assigned to QA- vibrations; these vibrations are also observed in the P+QA(-)-PQA and P+QB(-)-PQB difference spectra. Through an analysis of all of the static difference spectra, the electron-transfer pathway can be monitored in the infrared from the primary donor, P, to the secondary acceptor, QB, via the intermediate acceptor, I, and the primary acceptor, QA. The difference spectra are dominated by absorbance changes of prosthetic groups, with very few identifiable contributions from amino acids and little overall structural change in the protein backbone, involving only one or two residues for the various charge-separated states. Oxidation of the primary donor in the reaction center shows the characteristic absorbance changes of the 9-keto and 10-ester carbonyl groups observed upon oxidation of bacteriochlorophyll b in a non-hydrogen-bonded environment [Ballschmiter, K. H., & Katz, J. J. (1969) J. Am. Chem. Soc. 91, 2661-2677]. Reduction of the quinones in the reaction center yields absorbance changes of the carbonyls observed during reduction of quinones in a hydrogen-bonded environment [Bauscher, M., Nabedryk, E., Bagley, K., Breton, J., & Mäntele, W. (1990) FEBS Lett. 261, 191-195].(ABSTRACT TRUNCATED AT 250 WORDS)

Benzoquinones↗

PubMed1992

Internal radiation therapy for hepatocellular carcinoma. Results of a French multicenter phase II trial of transarterial injection of iodine 131-labeled Lipiodol.

Preliminary Phase I trials have shown iodine 131 (131I)-Lipiodol (ethiodized oil; Laboratoires Guerbet, Aulnaysous-Bois, France) to be well tolerated and most likely effective in the treatment of hepatocellular carcinoma (HCC). In this multicenter Phase II trial, the authors tested the feasibility and reproducibility of this treatment in other medical institutions and evaluated its efficacy in 50 patients with unresectable Stage I or II HCC, by the classification of Okuda et al. The authors studied 47 men and 3 women (63.9 +/- 7.1 years old) with Stage I (n = 18) or II (n = 32) HCC, by the classification of Okuda et al., which was verified by histologic findings (n = 25), cytologic findings (n = 11), or association of a tumor with alpha-fetoprotein serum values greater than 500 micrograms/l (n = 14). This multicenter trial (1) confirmed that the 131I-Lipiodol treatment is well tolerated; (2) showed that there is a high reproducibility of results with respect to other institutions and an objective tumor response in 40% of the cases; and (3) indicated the necessity of performing a randomized controlled study.

Adult↗

PubMed1992

Chromophore-protein interactions and the function of the photosynthetic reaction center: a molecular dynamics study.

The coupling between electron transfer and protein structure and dynamics in the photosynthetic reaction center of Rhodopseudomonas viridis is investigated. For this purpose molecular dynamics simulations of the essential portions (a segment of 5797 atoms) of this protein complex have been carried out. Electron transfer in the primary event is modeled by altering the charge distributions of the chromophores according to quantum chemical calculations. The simulations show (i) that fluctuations of the protein matrix, which are coupled electrostatically to electron transfer, play an important role in controlling the electron transfer rates and (ii) that the protein matrix stabilizes the separated electron pair state through rapid (200 fs) and temperature-independent dielectric relaxation. The photosynthetic reaction center resembles a polar liquid in that the internal motions of the whole protein complex, rather than only those of specific side groups, contribute to i and ii. The solvent reorganization energy is about 4.5 kcal/mol. The simulations indicate that rather small structural rearrangements and changes in motional amplitudes accompany the primary electron transfer.

Bacterial Chromatophores↗

PubMed1992

Lactitol or lactulose in the treatment of chronic hepatic encephalopathy: results of a meta-analysis.

Lactitol (beta-galactosido-sorbitol) has been recently compared with lactulose for the treatment of chronic hepatic encephalopathy in a few studies, each comprising a small number of patients. The results are controversial. We studied the efficiency and tolerance of both compounds by using a meta-analysis on the basis of published controlled trials. Our study only included controlled or randomized trials comprising cirrhotic patients with chronic hepatic encephalopathy. Analyzed parameters were the portosystemic encephalopathy index of Conn after treatment, the percentage of improved patients and the percentage of patients who had ill effects related to the treatment (flatulence, diarrhea). Bibliographical screening revealed five studies comparing the effects of lactitol and lactulose in chronic hepatic encephalopathy. Four crossover studies were done that included 48 patients and one parallel study that included 29 patients. The duration of the treatment ranged from 3 to 6 mo. All studies found a similar efficiency with both drugs. However, they exhibited some discrepancies in the relative frequency of adverse reactions (flatulence). Meta-analysis showed no statistical differences in the portosystemic encephalopathy index after lactitol or lactulose treatment. The percentage of improved patients after lactitol or lactulose was similar. In contrast, the analysis revealed a higher frequency (p less than 0.01) of flatulence in patients treated with lactulose compared with those treated with lactitol. In conclusion, this meta-analysis shows no statistical difference between therapeutic effects of lactitol and lactulose, but it does show a higher frequency of flatulence with lactulose. This suggests that lactitol should be preferred to lactulose for the treatment of chronic hepatic encephalopathy.

Chronic Disease↗

PubMed1992

Gln-41 is intermolecularly cross-linked to Lys-113 in F-actin by N-(4-azidobenzoyl)-putrescine.

The bifunctional reagent N-(4-azidobenzoyl)-putrescine was synthesized and covalently bound to rabbit skeletal muscle actin. The incorporation was mediated by guinea pig liver transglutaminase under conditions similar to those described by Takashi (1988, Biochemistry 27, 938-943); up to 0.5 M/M were incorporated into G-actin, whereas F-actin was refractory to incorporation. Peptide fractionation showed that at least 90% of the label was bound to Gln-41. The labeled G-actin was polymerized, and irradiation of the F-actin led to covalent intermolecular cross-linking. A cross-linked peptide complex was isolated from a tryptic digest of the cross-linked actin in which digestion was limited to arginine; sequence analysis as well as mass spectrometry indicated that the linked peptides contained residues 40-62 and residues 96-116, and that the actual cross-link was between Gln-41 and Lys-113. Thus the gamma-carboxyl group of Gln-41 must be within 10.7 A of the side chain (probably the amino group) of Lys-113 in an adjacent actin monomer. In the atomic model for F-actin proposed by Holmes et al. (1990, Nature 347, 44-49), the alpha-carbons of these residues in adjacent monomers along the two-start helices are sufficiently close to permit cross-linking of their side chains, and, pending atomic resolution of the side chains, the results presented here seem to support the proposed model.

Actins↗

PubMed1992

Molecular cloning, nuclear gene structure, and developmental expression of NADPH: protochlorophyllide oxidoreductase in pea (Pisum sativum L.).

Complementary DNA clones and a corresponding nuclear gene (lpcr) encoding the NADPH-dependent protochlorophyllide oxidoreductase (pchlide reductase, EC 1.6.99.1) have been characterized from pea (Pisum sativum L.). The pea lpcr gene encodes a 43,118 Da precursor polypeptide comprised of a transit peptide of 64 amino acids and a mature protein of 336 amino acids. The coding portion of the gene is interrupted by four introns, two of which are located within the transit peptide coding portion of the gene. The deduced primary structure for the pea protein is similar to those reported for Arabidopsis and two monocot species. Northern blot analysis revealed little to no decrease in steady-state levels of mRNA encoding the enzyme in etiolated leaves illuminated with continuous white light for up to 48 h. In contrast, western blot analysis showed that the major immunoreactive species present in whole leaf extracts decreased to nearly undetectable levels during this same 48 h period. These results suggest that pchlide reductase activity in pea is primarily regulated post-transcriptionally, most likely at the level of translation initiation/elongation or protein turnover.

Amino Acid Sequence↗

PubMed1992

Methyl tert-butyl ether in the endoscopic treatment of common bile duct radiolucent stones in elderly patients with nasobiliary tube.

Methyl tert-butyl ether is an effective dissolution agent for cholesterol stones. The aim of this work was to evaluate the effect of methyl tert-butyl ether on radiolucent common bile duct stones in patients in whom endoscopic extraction has failed. From September 1985 to September 1987, 1374 patients underwent endoscopic retrograde cholangiopancreatography in our Liver Unit. An endoscopic sphincterotomy was indicated in 195 patients with common bile duct (CBD) stones because of an age over 65 years and/or surgical contraindications. Endoscopic sphincterotomy was efficient in 187 patients, allowing complete stone removal in association with conventional endoscopic methods and mechanical lithotripsy in 170 patients. Twelve of the 17 patients with failure of conventional endoscopic treatments were either older than 75 years (11 patients; mean age, 86 +/- 4.5 years) or exhibited a surgical contraindication. Stones completely obstructed CBD in six patients and had a diameter exceeding 25 mm in the six other patients. These subjects were selected for stone dissolution by methyl tert-butyl either (MTBE) according to the following protocol. MTBE was directly infused into CBD through a nasobiliary catheter, twice daily for 4-13 days (mean, seven days). Bile duct opacification, repeated after MTBE treatment, revealed the complete disappearance of CBD stones in one patient, a decrease in stone size in five patients and no change in the six other patients. MTBE treatment was well tolerated except in three patients who complained from transient abdominal pains and nausea. At the second attempt of endoscopic treatment, CBD stones were found to be softened and easily broken up, allowing a complete clearance in six patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed1992

Selective downregulation of rat renal clearance receptors for atrial natriuretic peptide by chronic high-salt intake: study on isolated membranes using 125I-labelled c-atrial natriuretic peptide-(4-23).

1. 125I-labelled c-atrial natriuretic peptide-(4-23) was used as radioligand for the direct quantification of atrial natriuretic peptide clearance receptors, and 125I-labelled rat atrial natriuretic peptide-(1-28) was used for the determination of total and biologically active atrial natriuretic peptide receptors, in renal glomerular and papillary membrane preparations of chronically salt-loaded and control rats. 2. The membrane preparation technique included acid-washing (pH 5), and receptor binding was assessed by saturation studies at 4 degrees C for 3 h. Chronic salt loading revealed a 35% decrease in clearance receptor number in the glomerular membrane and a 42% decrease in the papillary membranes. The absolute decrease in clearance receptor number was almost identical with the observed reduction in absolute number of total atrial natriuretic peptide receptors. Biologically active receptors were not affected by chronic salt loading. 3. Selective downregulation of clearance receptors for atrial natriuretic peptide may reflect an important role for the rat renal atrial natriuretic peptide system in long-term fluid and electrolyte regulation.

Animals↗

PubMed1992

Acute colitis associated with prolonged administration of neuroleptics.

We describe a 29-year-old patient who developed acute colitis limited to the sigmoid and left colon with features mimicking ischemic injury after a prolonged administration of trifluoroperazine and levomepromazine, two phenothiazines in association with haloperidol, another neuroleptic, and biperidene, an anticholinergic compound. The discontinuation of these drugs was followed by a prompt and complete recovery, and no other cause of acute colitis was found. The subsequent administration of sultopride, a neuroleptic from the benzamide family and then the readministration of haloperidol were well tolerated. No colonic disorder occurred for the following months. This case strongly supports the view that neuroleptic agents, in particular phenothiazines, may induce acute colitis and that haloperidol, a butyrophenone derivative, or sultopride, a benzamide-related neuroleptic, can be administered thereafter without recurrence of the disease.

Adult↗

PubMed1992

Hepatitis associated with amoxycillin-clavulanic acid combination report of 15 cases.

Fifteen cases of hepatitis related to a combination of amoxycillin and clavulanic acid are reported. Most patients were aged 60 years or more and there were more men than women (sex ratio 4:1). The amoxycillin-clavulanic acid had been given at doses ranging from 0.5 to 6 g/day (mean 2 g/day) for seven to 60 days (mean 18 days). In 11 cases, the first symptoms appeared one to four weeks after stopping treatment. Jaundice was observed in all patients and was frequently associated with pruritus. Serum aminotransferase activities were increased in all patients and were generally two to 10 times the upper limit of normal. Serum alkaline phosphatase activity was considerably increased, from two to seven times the upper limit of normal. Histological examination of the liver, performed in seven patients, showed centri- or panlobular cholestasis in all cases, associated with granulomatous hepatitis in one. The prognosis of amoxycillin-clavulanic acid induced hepatitis seemed to be good. None of the patients exhibited biological or clinical features of hepatic failure and the course of the disease was characterised by the resolution of jaundice within one to eight weeks and a complete recovery within four to 16 weeks. Taking into account the number of treated subjects and reported cases, we estimated the risk of developing hepatitis with this drug combination to be very low, probably below 1/100,000. Our data suggest that the risk of hepatotoxicity may be increased in elderly men given lengthy treatment. The association of hepatitis and signs of hypersensitivity may suggest an immunoallergic mechanism of hepatotoxicity in some patients.

Adult↗