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Biomedical subjects

M Peter

Publications and source records attributed to M Peter.

At least 127 records · Page 7Linked to original sources
PubMed1994

Variability of pulsatile luteinizing hormone secretion in young male volunteers.

Characteristics of spontaneous pulsatile luteinizing hormone secretion were compared in ten young healthy men in three 24-h profiles obtained at intervals of 14 days and 3 months. The ages of the volunteers ranged from 19 to 25 years, and heights and weights were within normal limits. Blood samples were taken at 10-min intervals and plasma luteinizing hormone (LH) was determined in the same immunoradiometric assay using monoclonal antibodies. Conventional pulse detection was carried out with PULSAR and CLUSTER programs. In addition, a simultaneous multiple parameter DECONVOLUTION was applied. As a group, no significant differences between the three profile series were found for any of the calculated parameters of LH concentration or LH secretion. However, most parameters showed low correlation coefficients between the three study periods, suggesting that substantial individual variations might contribute to the more reliable group results. Median coefficients of variation (cv) for the individual subject ranged from 9.7% (interpulse interval and endogenous half-life) to 37.7% (mass per burst). However, the maximal individual cv observed was 78.4%. Intra-individual variability was lower than the variability between subjects for quantitative properties of LH concentration and secretion, although not significantly so for all parameters. In conventional pulse detection, the highest individual reliability was found for mean and integrated LH concentrations (median cv 10.2 and 13.7%, respectively), number of pulses per 24h (CLUSTER, median cv 12.2%), mean pulse amplitude (PULSAR, median cv 10%) and interpulse interval (CLUSTER, median cv 9.7%). In DECONVOLUTION analysis, the endogenous LH half-life (median cv 9.7%), secretory burst amplitude (median cv 14.8%) and interburst interval (median cv 14.5%) revealed the lowest intra-individual variation. In contrast, the half-duration of a secretory episode and the mass of LH secreted per burst proved to be the least reliable measures (median cv 32.7% and 37.7%, respectively). Calculated endogenous LH production rates correlated highly (p < 0.01) across all three sessions. The relative frequencies of the LH peak amplitudes/heights and peak widths (durations) showed almost identical distribution curves for all three sampling periods. In conclusion, a high reproducibility of group results for both integrative parameters and pulse characteristics of LH concentrations and secretion were found in normal men. However, intra-individual reliability was variable and at times considerable, depending on the parameter chosen. These observations suggest caution in the interpretation of single LH profiles from individual subjects or patients unless the variation reported herein is considered.

Adult↗
PubMed1994

Phonological codes are early sources of constraint in visual semantic categorization.

Two experiments were directed at early phonological activation in the semantic categorization task. In Experiment 1, briefly exposed targets homophonic to category exemplars (ROWS for the category A FLOWER), and their graphemic controls (ROBS), were judged for category membership with and without a backward pattern mask. False positives were greater for ROWS than ROBS to the same degree under both unmasked and masked conditions. In Experiment 2, false positives were examined in the semantic categorization task under backward dichoptic masking by pseudowords that were, in turn, masked monoptically by a pattern mask. Briefly exposed homophones (e.g., WEAK), masked by a phonologically similar pseudoword ("feek"), a graphemic control ("felk"), or an unrelated pseudoword ("furt"), were categorized as category exemplars (A UNIT OF TIME). The difference in false positives was significant for WEAK-feek versus WEAK-furt, but not for WEAK-felk versus WEAK-furt. It was suggested that the persistence of the homophonic effects under the pattern masking of Experiment 1 and their amplification under the phonological masking of Experiment 2 were because phonological codes cohere rapidly and provide, thereby, immediately available constraints on semantic processing.

Adult↗
PubMed1993

FAR1 links the signal transduction pathway to the cell cycle machinery in yeast.

Alpha factor induces arrest of yeast a cells in G1 and transcription of genes involved in mating. Prior work indicates that FUS3, a member of the MAP kinase family, and FAR1, whose molecular activity is unknown, contribute to cell cycle arrest by inhibiting G1 cyclins. Here we show that FAR1 is a substrate for FUS3 and that this phosphorylation regulates association of FAR1 with CDC28-CLN2 kinase. We show also that FAR1 is phosphorylated in vitro by the CDC28-CLN2 complex and in vivo in a CDC28-dependent manner. Mutational analysis of FAR1 reveals a correlation between its ability to associate with CDC28-CLN2 and to arrest the cell cycle. These results suggest that FAR1 protein is the link between the signaling pathway and the cell cycle machinery.

Amino Acid Sequence↗
PubMed1993

Combinatorial generation of variable fusion proteins in the Ewing family of tumours.

Balanced translocations involving band q12 of human chromosome 22 are the most frequent recurrent translocations observed in human solid tumours. It has been shown recently that this region encodes EWS, a protein with an RNA binding homologous domain. In Ewing's sarcoma and malignant melanoma of soft parts, translocations of band 22q12 to chromosome 11 and 12 result in the fusion of EWS with the transcription factors FLI-1 and ATF1, respectively. The present analysis of 89 Ewing's sarcomas and related tumours show that in addition to the expected EWS-FLI-1 fusion, the EWS gene can be fused to ERG, a transcription factor closely related to FLI-1 but located on chromosome 21. The position of the chromosome translocation breakpoints are shown to be restricted to introns 7-10 of the EWS gene and widely dispersed within introns 3-9 of the Ets-related genes. This heterogeneity generates a variety of chimeric proteins that can be detected by immuno-precipitation. On rare occasions, they may be associated with a truncated EWS protein arising from alternate splicing. All 13 different fusion proteins that were evidenced contained the N-terminal domain of EWS and the Ets domain of FLI-1 or ERG suggesting that oncogenic conversion is achieved by the linking of the two domains with no marked constraint on the connecting peptide.

Amino Acid Sequence↗
PubMed1993

Diagnosis and treatment of 17-hydroxylase deficiency.

Leading symptoms of 17-hydroxylase/17,20-lyase deficiency in childhood are hypertension and hypokalemia. We found this enzyme defect in 3 phenotypically female siblings aged 12, 15 and 16 years. Two of the sibs have a 46,XY chromosome pattern, the third is genetically female. Pubertal development did not occur. Both of the 46,XY sibs have male internal and female external genitalia. The 46,XX sister has normal female internal genitalia. At the time of diagnosis, two of the three siblings had hypertension (RR between 190/135 and 160/110 mmHg). Two of the three siblings had low serum potassium and metabolic alkalosis. All three patients had excessively high plasma levels of 11-deoxycorticosterone (DOC) and corticosterone. Aldosterone was also elevated whereas plasma renin activity was suppressed. Plasma cortisol and its 17-hydroxylated precursors were low, as were plasma testosterone, dihydroepiandrosterone sulphate and estradiol, while the gonadotropins LH and FSH were elevated in all three patients. We studied the steroid profiles of these three patients during long term glucocorticoid treatment with dexamethasone, which is now followed for 13 years. Blood pressure and serum potassium became normal. Plasma aldosterone, corticosterone and DOC were clearly lower but not fully normalized. The two genetically male sisters obtained estrogens for induction of female secondary sex characteristics. The third 46,XX sister has normal menstruations during substitution with cyclic estrogen/gestagen therapy. All three patients lack pubic and axillary hair, and reached normal adult heights both for phenotypic sex and for target height. The psychosocial orientation is female in all of them. Apart from rare reports of development of malignant hypertension, prognosis is better than in other enzyme deficiencies causing congenital adrenal hyperplasia since no Addisonian crises occur due to DOC and corticosterone overproduction resulting in apparently normal endogenous glucocorticoid activity.

Adolescent↗
PubMed1993

Genomic structure of the EWS gene and its relationship to EWSR1, a site of tumor-associated chromosome translocation.

The EWS gene has been identified based on its location at the chromosome 22 breakpoint of the t(11;22)(q24;q12) translocation that characterizes Ewing sarcoma and related neuroectodermal tumors. The EWS gene spans about 40 kb of DNA and is encoded by 17 exons. The nucleotide sequence of the exons is identical to that of the previously described cDNA. The first 7 exons encode the N-terminal domain of EWS, which consists of a repeated degenerated polypeptide of 7 to 12 residues rich in tyrosine, serine, threonine, glycine, and glutamine. Exons 11, 12, and 13 encode the putative RNA binding domain. The three glycine- and arginine-rich motifs of the gene are mainly encoded by exons 8-9, 14, and 16. The DNA sequence in the 5' region of the gene has features of a CpG-rich island and lacks canonical promoter elements, such as TATA and CCAAT consensus sequences. Positions of the chromosome 22 breakpoints were determined for 19 Ewing tumors. They were localized in introns 7 or 8 in 18 cases and in intron 10 in 1 case.

Amino Acid Sequence↗
PubMed1993

Phosphorylation on protein kinase C sites inhibits nuclear import of lamin B2.

The nuclear lamina is a karyoskeletal structure at the nucleoplasmic surface of the inner nuclear membrane. Its assembly state is regulated by phosphorylation of the intermediate filament type lamin proteins. Strong evidence has been obtained for a causal link between phosphorylation of lamins by the p34cdc2 protein kinase and disassembly of the nuclear lamina during mitosis. In contrast, no information is currently available on the role of lamin phosphorylation during interphase of the cell cycle. Here, we have identified four protein kinase C phosphorylation sites in purified chicken lamin B2 as serines 400, 404, 410, and 411. In vivo, the tryptic peptide containing serines 400 and 404 is phosphorylated throughout interphase, whereas serines 410 and 411 become phosphorylated specifically in response to activation of protein kinase C by phorbol ester. Prompted by the close proximity of serines 410/411 to the nuclear localization signal of lamin B2, we have studied the influence of phosphorylation of these residues on nuclear transport. Using an in vitro assay, we show that phosphorylation of lamin B2 by protein kinase C strongly inhibits transport to the nucleus. Moreover, phorbol ester treatment of intact cells leads to a substantial reduction of the rate of nuclear import of newly synthesized lamin B2 in vivo. These findings have implications for the dynamic structure of the nuclear lamina, and they suggest that the modulation of nuclear transport rates by cytoplasmic phosphorylation may represent a general mechanism for regulating nuclear activities.

Amino Acid Sequence↗
PubMed1993

Comparison of complete and incomplete suppression of pituitary-gonadal activity in girls with central precocious puberty: influence on growth and predicted final height. The German-Dutch Precocious Puberty Study Group.

The question as to whether treatment with short-acting or with slow-release gonadotropin-releasing hormone (GnRH) agonists has different effects on growth and bone maturation when treating girls with central precocious puberty has not yet been studied. In a meta-analysis, we compared 21 naive girls with central precocious puberty who were treated with buserelin with 22 naive girls with central precocious puberty who received Decapeptyl in depot form. Treatment lasted for at least 18 months. At the start of therapy, chronological age, bone age, growth velocity and pubertal stage in the two groups were very similar. During the first 6 months of treatment, significantly more phases of incomplete suppression of pituitary-gonadal activity occurred in the buserelin group. As a result, growth velocity and bone maturation (delta bone age/delta chronological age) remained significantly higher than in the Decapeptyl Depot group (p < 0.0001 and p < 0.01, respectively). In contrast to the Decapeptyl Depot group, the height standard deviation score (SDS) for bone age in the buserelin group did not change significantly in the first 6 months of treatment, and the predicted adult height decreased. Between the 6th and 18th months of therapy, the development of growth rate, delta bone age/delta chronological age, height SDS for bone age and predicted adult height in both groups became almost identical. However, the rate of growth and bone maturation in the buserelin group remained faster than in the Decapeptyl group, though not significantly so. The mean predicted adult height had risen significantly after 18 months in the Decapeptyl Depot group but not in the group treated with buserelin.(ABSTRACT TRUNCATED AT 250 WORDS)

Body Height↗
PubMed1993

Progression of aortic stenosis. Role of age and concomitant coronary artery disease.

To determine the spontaneous progression of valvular aortic stenosis and to delineate clinical factors related to progression, a longitudinal study, including 49 patients (aged 16 to 81 years), was performed. All patients had auscultatory findings of aortic stenosis and multiple Doppler echocardiograms separated by at least 11 months. Rapid progression of aortic stenosis was defined as an increase of maximal instantaneous pressure gradient by > or = 10 mm Hg per year. During a mean follow-up period of 32 months (11 to 66 months), maximal pressure gradient rose from 38 +/- 15 to 60 +/- 20 mm Hg in the entire study population, resulting in a median increase of 7.2 mm Hg per year. In 21 patients (43 percent), an increase of > or = 10 mm Hg per year was found; in this subgroup with rapid progression, patients were older (64 vs 53 years, p < 0.01) and coronary artery disease was more prevalent (38 percent vs 7 percent, p = 0.01). We conclude that nearly half the patients with initially mild to moderate valvular aortic stenosis reveal a progression of > or = 10 mm Hg per year.

Adolescent↗
PubMed1993

The Omnicarbon tilting-disc heart valve prosthesis. A clinical and Doppler echocardiographic follow-up.

From 1986 to 1990, 172 patients with a median age of 60.5 years (range 20 to 79 years) received 187 Omnicarbon valves (109 aortic valve replacements, 48 mitral valve replacements, and 15 double valve replacements). Patients were followed-up for a median observation period of 2.5 years (range 4 months to 5.2 years) by clinical and Doppler echocardiographic examination. Follow-up was complete in 98%. Operative mortality (death within 30 days) was 1.7%, and linearized late mortality was 2.6% per patient-year, corresponding to an actuarial survival rate for operative survivors of 89% after 4 years. The overall 4-year postoperative survival was 87% (93% for aortic valve replacement, 77% for mitral valve replacement). Compared with age- and sex-adjusted Swiss death rates, there was an excess mortality of 5% after 4 years. Percentages for freedom from valve-related complications at 4 years are as follows: thromboembolism, 98% (aortic valve replacement, 98%, and mitral valve replacement, 96%); anticoagulant-related hemorrhage, 95%; valve endocarditis, 96%; reoperation, 96%; and permanent valve-related impairment, 99%. The overall 4-year event-free survival was 76% (80% for aortic valve replacement and 69% for mitral valve replacement). New York Heart Association class improved in 88% of the patients by 1 to 3 grades, and only 3% remained in class III after operation. For the most commonly used aortic valve (23 mm), Doppler echocardiography revealed a peak pressure gradient of 29 +/- 10 mm Hg, a fractional shortening/peak pressure gradient ratio of 1.34 +/- 0.61, and a performance index of 0.35 +/- 0.08. In the most commonly used mitral valve (27 mm), the mean pressure gradient was 4.0 +/- 2.1 mm Hg. We conclude that excellent clinical and hemodynamic results can be obtained with the Omnicarbon prosthesis, in both the aortic and mitral positions.

Adult↗
PubMed1992

[Ischemic cerebrovascular seizure: when and how should one search for a cardiac embolism source?].

Cerebral embolism originating from the heart accounts for approximately 15 to 20% of ischemic strokes. By far the most important source for cardiac embolism is associated with atrial fibrillation; in these patients immediate anticoagulation with no further echocardiographic diagnostic is recommended. The majority of the remaining cardiac sources of embolism--they originate from the left ventricle and the valves--can be suggested by clinical signs. In these cases a documentation by echocardiography is indicated. In contrast, embolism originating from the left atrium is rare and commonly not detectable by simple clinical means. The semi-invasive transesophageal echocardiography is able to visualize atrial pathologies with a high accuracy, but this investigation should be performed routinely only in patients less than 45 years old with no evidence for cardiac disease.

Atrial Fibrillation↗
PubMed1992

PCR assay for chromosome 1p deletion in small neuroblastoma samples.

Deletion of the short arm of chromosome 1 is among the most recurrent cytogenetic alterations found in neuroblastoma and has been associated with short survival. However, this prognostic information, which relies on time-consuming techniques, is not yet routinely exploited. In order to set up a reliable and simple routine test to determine 1p deletion in neuroblastoma, we have used the polymerase chain reaction to genotype neuroblastoma DNA at 2 loci containing a variable number of tandem repeats and located on the distal part of the short arm of chromosome 1. Agarose gel electrophoresis and ethidium bromide staining of the amplification products enable a simple determination of constitutional and tumor genotypes at these loci to be made. A total of 37 samples from 29 patients were studied with this technique. Loss of heterozygosity (LOH) could be identified in 8 cases. In each case the results obtained were in agreement with those achieved by the Southern procedure. This technique will be of particular interest in the pretherapeutic analysis of 1p deletions in small tumor samples obtained by fine-needle aspirates of the primary tumor. It should also enable retrospective studies from paraffin-embedded tumor fragments to be made and provide information for the analysis of tumor heterogeneity in neuroblastoma and in other tumors with 1p deletions.

Base Sequence↗
PubMed1992

Gene fusion with an ETS DNA-binding domain caused by chromosome translocation in human tumours.

Ewing's sarcoma and related subtypes of primitive neuroectodermal tumours share a recurrent and specific t(11;22) (q24;q12) chromosome translocation, the breakpoints of which have recently been cloned. Phylogenetically conserved restriction fragments in the vicinity of EWSR1 and EWSR2, the genomic regions where the breakpoints of chromosome 22 and chromosome 11 are, respectively, have allowed identification of transcribed sequences from these regions and has indicated that a hybrid transcript might be generated by the translocation. Here we use these fragments to screen human complementary DNA libraries to show that the translocation alters the open reading frame of an expressed gene on chromosome 22 gene by substituting a sequence encoding a putative RNA-binding domain for that of the DNA-binding domain of the human homologue of murine Fli-1.

Amino Acid Sequence↗