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S Mohr

Publications and source records attributed to S Mohr.

54 records · Page 3Linked to original sources
PubMed1997

Characterization of Neurospora mitochondrial group I introns reveals different CYT-18 dependent and independent splicing strategies and an alternative 3' splice site for an intron ORF.

The Neurospora crassa mitochondrial tyrosyl-tRNA synthetase (CYT-18 protein) functions in splicing the N. crassa mitochondrial large rRNA intron by stabilizing the catalytically active structure of the intron core. Here, a comprehensive study of N. crassa mtDNA group I introns identified two additional introns, cob-I2 and the ND1 intron, that are dependent on CYT-18 for splicing in vitro and in vivo. The other seven N. crassa mtDNA group I introns are not CYT-18-dependent and include five that self-splice and two that do not splice under any conditions examined. Some of these introns may require maturases or other proteins for efficient splicing. All but one of the non-CYT-18-dependent introns contain large peripheral extensions of the P5 stem, related to the P5abc structure that blocks CYT-18 binding to the Tetrahymena large rRNA intron. The remaining non-CYT-18-dependent intron, cob-I1, contains a long, peripheral extension of the P9 stem, denoted P9.1, which also impedes CYT-18 binding. Detailed analysis of the CYT-18-dependent ND1 intron showed that two 3' splice sites are used in vitro and in vivo. The proximal, alternative 3' splice site brings the intron open reading frame, which potentially encodes a mobility endonuclease, in frame with the upstream exon, possibly providing a means of expression. Considered together, our results show that group I introns in N. crassa mitochondria use a variety of strategies involving different proteins and/or RNA structures to assist splicing, and they support the hypothesis that CYT-18 and the peripheral RNA structure P5abc are alternative evolutionary adaptations for stabilizing the active structure of the intron core.

Alternative Splicing↗
PubMed1996

Cloning and characterization of the Neurospora crassa cyt-5 gene. A nuclear-coded mitochondrial RNA polymerase with a polyglutamine repeat.

The Neurospora crassa mutants, cyt-5-1 and cyt-5-4 have a cytochrome b- and aa3-deficient phenotype, suggesting that they result from a deficiency in a nuclear-coded component of the mitochondrial gene expression apparatus (Bertrand, H., Nargang, F. E., Colllins, R. A., and Zagozeski, C. A. (1977) Mol. Gen. Genet. 153,247-257). The complementing wild-type gene has been cloned and and shown to encode a protein with significant sequence similarity to Saccharomyces cerevisiae mitochondrial RNA polymerase and bacteriophage RNA polymerases. There are remarkable differences between the N. crassa protein and its yeast homologue, including a region of very little homology near the N termini of the two gene products. The cyt-5 gene encodes a stretch of polyglutamine in this region of uniquesequence. In addition, an acidic insertion (86 amino acids, of which 24 are Asp or Glu and 10 are Arg or Lys) is present near the C terminus of the cyt-5 gene product. Transcript levels of the cytochrome b and cytochrome oxidase subunit III genes are severely reduced in cyt-5 mutants, suggesting a likely mechanism for the cytochrome-deficient phenotype. In contrast, mitochondrial rRNAs accumulate to nearly normal levels in cyt-5 mutants. However, mitochondrial rRNA levels are not indicative of the rate of transcription of the corresponding genes, since crude lysates of mitochondria from cyt-5 mutants exhibit greatly reduced transcriptional activity with a 19 S rRNA promoter. The cyt-5 gene is flanked by at least one gene whose product also may be involved in mitochondrial function.

Amino Acid Sequence↗
PubMed1996

Posttranslational modification of glyceraldehyde-3-phosphate dehydrogenase by S-nitrosylation and subsequent NADH attachment.

Nitric oxide (NO)-related activity has been associated with an NAD+-dependent modification of the glycolytic enzyme, glyceraldehyde-3-phosphate dehydrogenase (GAPDH). However, the mechanism by which NO effects covalent attachment of nucleotide and its role in regulation of enzyme activity are controversial. Recent studies have shown that S-nitrosylation of GAPDH (Cys149) initiates subsequent modification by the pyridinium cofactor. Here we show that NADH rather than NAD+ is the preferred substrate. Transnitrosation from active site S-nitrosothiol to the reduced nicotinamide ring system appears to facilitate protein thiolate attack on the enzyme-bound cofactor. This results in attachment of the intact NADH molecule. Moreover, we find that S-nitrosylation of GAPDH is responsible for reversible enzyme inhibition, whereas attachment of NADH accounts for irreversible enzyme inactivation. S-Nitrosylation may serve to protect GAPDH from oxidant inactivation in settings of cytokine overproduction and to regulate glycolysis. NADH attachment is more likely to be a pathophysiological event associated with inhibition of gluconeogenesis.

Animals↗
PubMed1996

Protein thiol modification and apoptotic cell death as cGMP-independent nitric oxide (NO) signaling pathways.

Nitric oxide signaling is achieved through both cGMP-dependent and cGMP-independent mechanisms. The latter are exemplified by protein thiol modification followed by subsequent NAD(+)-dependent automodification of the glycolytic enzyme GAPDH, or by mechanisms inducing accumulation of the tumor suppressor gene p53 and causing apoptotic cell death. Both cGMP-independent actions are initiated using NO-releasing compounds and an active LPS/cytokine-inducible NO synthase. NO-synthase inhibitors block the release of NO and hinder downstream signaling mechanisms; they are therefore valuable pharmacological tools linking a defined cellular response to various NO actions. Signal transducing mechanisms elicited by NO can be studied using GAPDH as a representative example of NO-induced protein modification and are grouped as follows: --S-Nitrosylation reactions initiated by NO+ --NAD(+)-dependent, post-translational covalent automodification of GAPDH --Oxidative modification (thiol oxidation) and inhibition of GAPDH by NO-related agents, probably ONOO- GAPDH and several other protein targets may serve as molecular sensors of elevated NO concentrations and may transmit this message through posttranslational modification and oxidation-induced conformational changes as cGMP-independent NO signaling pathways. Toxicity of NO seems to be linked to both apoptosis and necrosis, depending on the chemistry of NO it undergoes in a given biological milieu. Toxicity manifests as a relative excess of NOx, metal-NO interactions, and ONOO- formation in relation to cellular defense systems. Although accumulation of the tumor-suppressor gene product p53 in response to NO opens a regulatory mechanism known to be involved in apoptotic cell death, cGMP-independent signaling pathways remain to be elucidated. As NO-dependent modification of GAPDH would imply down-regulation of glycolysis and concomitant energy production followed by cell death, our data so far do not support this assumption. In recent years, NO has proved to be a beneficial messenger with a potentially toxic activity. It will be challenging to investigate NO biochemistry in closer detail and to elucidate how NO targets biological systems, especially in relation to its pathophysiological role.

Animals↗
PubMed1995

The VS catalytic RNA replicates by reverse transcription as a satellite of a retroplasmid.

The mitochondria of certain natural isolates of Neurospora contain both the Varkud plasmid, which encodes a reverse transcriptase, and a small unrelated RNA (VS RNA) that performs RNA-mediated self-cleavage and ligation reactions. Here, we show that VS RNA is transcribed from a VS plasmid DNA template by the Neurospora mitochondrial RNA polymerase using a promoter located immediately upstream of the RNA self-cleavage site that generates monomeric transcripts. VS RNA is then reverse transcribed by the Varkud plasmid reverse transcriptase to yield a full-length (-) strand cDNA, a predicted replication intermediate. Combined with previous genetic evidence, our results indicate that the VS plasmid replicates by reverse transcription as a satellite of the Varkud plasmid. This mode of replication, unprecedented for a satellite RNA, likely reflects the promiscuity of the Varkud plasmid reverse transcriptase, which does not require a specific primer to initiate cDNA synthesis. Our findings indicate how primitive reverse transcriptases with similar relaxed specificity could have facilitated the evolution of new retroelements.

Base Sequence↗
PubMed1995

Activin A and retinoic acid synergize in cyclooxygenase-1 and thromboxane synthase induction during differentiation of J774.1 macrophages.

The murine macrophage cell line J774.1 was used to study the development of prostanoid biosynthesis under the influence of activin A and retinoic acid. Treatment of cells with 3 nM activin A for 48 h increased the biosynthesis of the prostaglandins E2, D2, F2 alpha and thromboxane A2 more than fourfold due to an induction of cyclooxygenase-1 while cyclooxygenase-2 was unaffected. Transforming growth factor-beta acted in a similar way. Retinoic acid, when present alone, was without effect on the total cyclooxygenase products and only slightly changed the pattern of prostanoids. However, when coincubated with activin A, retinoic acid specifically induced the synthesis of thromboxane-A-synthase-specific mRNA and induced an increase in enzyme activity with a synergistic effect on cyclooxygenase-1 protein and mRNA. JunB, but not c-jun, mRNA expression was found under these conditions in addition to a transient c-fos mRNA increase. The combination of activin A and retinoid acid may be regarded as a differentiation model to study the development of cell-specific prostanoid patterns in macrophages and possibly other differentiating cells.

Activins↗
PubMed1994

Mechanism of covalent modification of glyceraldehyde-3-phosphate dehydrogenase at its active site thiol by nitric oxide, peroxynitrite and related nitrosating agents.

Previous studies have suggested that glyceraldehyde-3-phosphate dehydrogenase (GAPDH) undergoes covalent modification of an active site thiol by a NO.-induced [32P]NAD(+)-dependent mechanism. However, the efficacy of GAPDH modification induced by various NO donors was found to be independent of spontaneous rates of NO. release. To further test the validity of this mechanism, we studied the effects of nitrosonium tertrafluoroborate (BF4NO), a strong NO+ donor. BF4NO potently induces GAPDH labeling by the radioactive nucleotide. In this case, the addition of thiol significantly attenuates enzyme modification by competing for the NO moiety in the formation of RS-NO. Peroxynitrite (ONOO-) also induces GAPDH modification in the presence of thiol, consistent with the notion that this species can transfer NO+ (or NO2+) through the intermediacy of RS-NO. However, the efficiency of this reaction is limited by ONOO- -induced oxidation of protein SH groups at the active site. ONOO- generation appears to account for the modification of GAPDH by SIN-1. Thus, S-nitrosylation of the active site thiol is a prequisite for subsequent post-translational modification with NAD+, and emphasizes the role of NO+ transfer in the initial step of this pathway. Our findings thus provide a uniform mechanism by which nitric oxide and related NO donors initiate non-enzymatic ADP-ribosylation (like) reactions. In biological systems, endogenous RS-NO are likely to support the NO group transfer to thiol-containing proteins.

Adenosine Diphosphate Ribose↗
PubMed1994

Raynaud's phenomenon associated with the use of pneumatically powered surgical instruments.

Five patients developed symptoms of Raynaud's phenomenon and upper extremity paresthesias after 7-32 months of exposure to air-powered surgical instruments used for the harvest of bone for bone banks. Results of cold challenge plethysmography, nerve conduction studies, vibrotactile thresholds, and quantitative sensory testing were as follows: all patients had significant reproducible vasospasm with nondetectable finger systolic blood pressure (FSBP = 0) after local digital cooling; nerve conduction abnormalities included delayed median nerve sensory conduction (< 48 m/s) across 5 of 10 wrists; and no ulnar nerve abnormalities were detected. Vibrotactile thresholds were only modestly elevated, an unexpected outcome given the frequently recognized association between vibrotactile tests and nerve conduction studies. These abnormalities occurred with exposures to frequencies previously thought to be too high to be harmful to medical personnel.

Adult↗
PubMed1990

Assessment of hepatic function. Comparison of caffeine clearance in serum and saliva during the day and at night.

Hepatic microsomal function was assessed by a caffeine clearance test at night and during the day using saliva and serum samples obtained simultaneously. In 26 patients with cirrhosis, 21 patients with noncirrhotic liver disease and 15 control subjects caffeine elimination correlated well during the day and at night (r = 0.915 for serum and 0.917 for saliva). The correlation coefficients for caffeine clearance in saliva and serum were 0.940 during the day and 0.963 overnight. In the cirrhotic patients, clearance differed significantly from noncirrhotic liver disease and controls in saliva samples overnight: 0.51 +/- 0.45 ml/min per kg versus 0.91 +/- 0.44 and 1.41 +/- 0.56, respectively. Comparable results were obtained for serum clearance overnight and clearances during the day. Serum and saliva clearances at night correlated well with the aminopyrine breath test (rs = 0.884 and 0.907, respectively). Overnight caffeine clearance in saliva might be a simple useful method for assessing progression and prognosis of liver disease.

Aminopyrine↗
PubMed1984

Stage D1 adenocarcinoma of prostate.

The natural history of Stage D1 adenocarcinoma of the prostate remains unclear. In a series of 50 patients with positive pelvic lymph nodes at the time of staging lymphadenectomy, metastatic disease developed in 43 per cent of the patients treated for cure within the period of time of follow-up. Several series from the literature confirm those findings. Positive pelvic lymph nodes most probably represent systemic disease, and the patients are incurable by current surgical and radiotherapeutic modalities.

Adenocarcinoma↗
PubMed1984

Acid phosphatase: its influence on the management of carcinoma of the prostate.

Of 343 patients who underwent pelvic lymph node dissection during treatment for carcinoma of the prostate 25 had persistently elevated serum enzymatic acid phosphatase levels preoperatively: 15 (60 per cent) had metastases to the pelvic lymph nodes and 10 (40 per cent) had negative nodes. Bone metastases occurred in 10 of 12 (83 per cent) and 5 of 7 patients (71 per cent), respectively, who were followed for a minimum of 2 years. Of the 318 patients with normal serum enzymatic phosphatase levels 70 (22 per cent) had positive nodes. A persistently elevated serum enzymatic acid phosphatase level in patients with proved carcinoma of the prostate, with elimination of infrequent causes of enzyme elevation, indicates metastases and has significant implications regarding staging and, thus, therapy of this disease.

Acid Phosphatase↗
PubMed1982

Stroke risk from symptomless extracranial arterial disease.

The natural history of a prospectively selected group of neurologically symptomless patients with extracranial arterial disease (EAD) was studied. 23 of 122 patients died over a period of follow-up of from eleven to thirty-six months (mean = seventeen), but only 3 from stroke and 10 from cardiac failure. Among those patients still alive 8 reported transient ischaemic attacks, 1 a stroke, and 90 remain symptomless. Thus, by life-table analysis, the cumulative stroke rate was only 7%, irrespective of death or survival, the same as the average risk of death in a normal population. However, by subsequent continuous-wave Doppler examination of carotid and vertebral arteries, the probability of EAD progression was 85%. Involvement of initially unaffected arteries occurred either alone (25) or in combination with a deterioration of the original stenosis (14)--the latter alone was seen in 9 patients. A combined carotid and vertebral lesion was found to be the only significant indicator of cerebrovascular risk, which was six times greater than that for unilateral or bilateral carotid lesions.

Arterial Occlusive Diseases↗
PubMed1975

Perineal neoplasms.

Experience with 2 cases of neurally-derived perineal masses is described. A relevant review of the literature spanning 50 years revealed 36 cases of perineal neoplasm of diverse nature, disclosing that such lesions typically present as otherwise asymptomatic enlarging masses and may comprise a broad spectrum of neoplasia with diagnosis and prognosis often relating to the age of the patient. Management naturally relates to tissue type and degree of local involvement.

Adult↗
PubMedDate not supplied

[Validation of the French Version of the Life Skills Profile with people suffering of schizophrenia].

INTRODUCTION: Since the discovery of neuroleptics and the reintegration of people with schizophrenia in the community, psycho-social reeducation became an essential part of the treatment. The Life Skills Profile is a tool of reference for assessment of the dimensions, which have an impact on the adaptation in community. Each item describes an observable behavior, written in common language, to allow the care-givers and the family to evaluate it without having a specific formation. The long version (39 items) is recommended for therapeutic interventions with a person and the short one (20 items) for large scale studies on outcome in community. AIM OF THE STUDY: In order to dispose of a measure of function and disability in schizophrenia, we have translated the Life Skills Profile (LSP) in French and tested the validity of this translation for the long version (39 items) and the short ones (16 and 20 items). The 4 dimensions of the 16-items version--"withdrawal", "self-care", "compliance" and "antisocial"--were used for people with mental disorders and the 20-items version enhanced with a fifth dimension "bizarre", especially useful for people with schizophrenia. METHOD: 175 people suffering of schizophrenia (DSM IV, codes F20.0 to F20.5) were evaluated by their caregivers in 3 settings: psychiatric hospital, ambulatory care and sheltered homes. Confirmatory factorial analyses were performed to test the dimensional models and their psychometric characteristics were established. RESULTS: The original structure in 5 dimensions of the long version (39 items) is not confirmed. However, the short versions in 16 and 20 items were confirmed, without any modification. The required psychometric qualities of reliability and validity of the 20-items version were fulfilled. The inter-rater reliability ranged from 0.65 to 0.75 for the 5 dimensions; the test-retest reliability ranged from 0.80 to 0.91 and the internal consistency from 0.67 to 0.81. The validity was evaluated by comparison of the LSP scores upon living arrangements (people living in sheltered homes had lesser scores) and pathologies (19 people with severe major depression had higher scores). CONCLUSION: The 39-items version of the Life Skills Profile was not validated in French. However, for clinical practice of social rehabilitation, this tool remains useful for a single person to check specific behaviors, which could hinder his/her integration into the community, to plan specific interventions and to evaluate changes, in addition with other scales. By the validation of the short version of the Life Skills Profile, an instrument is at disposal in French for outcome studies which allow to: 1) quickly assess the social functioning of person suffering of schizophrenia by a caregiver or a family member; 2) to detect insufficient skills in specific domains; and 3) to evaluate therapeutic efficiency.

Adaptation, Psychological↗
PubMedDate not supplied

Genetically and medically susceptible workers.

The likelihood of an individual becoming ill from a hazardous material or condition is strongly influenced by both their genetic makeup and their underlying state of health. Although the past decade has seen great advances in understanding human variation in health and genetic polymorphisms and in the diagnosis and treatment of disease, much less progress has been made in effectively using this information to protect worker health. Scientific evidence for increased susceptibility often is weak and rarely satisfies legal thresholds for sufficient risk to warrant exclusion from a particular job. When public safety is a major concern, many legally mandated exclusions are not well justified. Medical opinions about fitness to work should be based upon a systematic and credible analysis of the condition, its relationship to ability and risk for a particular job, and knowledge of possible accommodations. Conclusions should reflect the limitations of scientific knowledge and guidance from antidiscrimination legislation.

Disability Evaluation↗
PubMedDate not supplied

[Population exposure to pollutants--selected examples from Schleswig-Holstein].

Environmental health policy aims at protecting human health against toxic, cancerogenic, mutagenic, teratogenic and other damaging influences. Environmental toxicology must assess the risk of environmental pollutants by monitoring exposure, characterising hazards, and proposing preventive measures. Examples of the cooperation between Public Health departments and the Bureau of Environmental Toxicology of Slesvig-Holstein are presented.

Carcinogens↗