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Biomedical subjects

M Peter

Publications and source records attributed to M Peter.

At least 19 recordsLinked to original sources
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↗
PubMed1992

Mitogen-activated protein kinases phosphorylate nuclear lamins and display sequence specificity overlapping that of mitotic protein kinase p34cdc2.

Members of the mitogen-activated protein (MAP) kinase family are implicated in mediating entry of cells into the cell cycle, as well as passage through meiotic M phase. These kinases have attracted much interest because their activation involves phosphorylation on both tyrosine and threonine residues, but little is known about their physiological targets. In this study, two distinct members of the MAP kinase family (p44mpk and p42mapk) are shown to phosphorylate chicken lamin B2 at a single site identified as Ser16. Moreover, these MAP kinases cause depolymerization of in-vitro-assembled longitudinal lamin head-to-tail polymers. Ser16 was previously shown to be phosphorylated during mitosis in vivo, and to be a target of the mitotic protein kinase p34cdc2 in vitro. Accordingly, lamins were proposed to be direct in vivo substrates of p34cdc2. This proposal is supported by quantitative analyses indicating that lamin B2, when assayed in vitro, is a substantially better substrate for p34cdc2 than for MAP kinases. Nevertheless, a physiological role of MAP kinases in lamin phosphorylation is not excluded. The observation that members of the MAP kinase family display sequence specificities overlapping that of p34cdc2 raises the possibility that some of the purported substrates of p34cdc2 may actually be physiological substrates of MAP kinases.

Animals↗
PubMed1992

Cloning and characterization of the Ewing's sarcoma and peripheral neuroepithelioma t(11;22) translocation breakpoints.

Ewing's sarcoma (ES) and peripheral neuroepithelioma (PN) are related tumors, possibly of neural crest origin, which are cytogenetically characterized by the specific translocation t(11;22)(q24;q12). The cos5 locus, previously identified in the vicinity of the chromosome 22 breakpoint of this translocation, was shown by in situ hybridization on interphase nuclei to lie between VIIIF2 and LIF, two loci located on either side of the breakpoint and at a distance of less than 2,000 kb. The progressive expansion of this locus by chromosome walking led to the construction of a 300 kb contig, which finally crossed the breakpoint. The subsequent cloning of the two translocation junction fragments of a PN, followed by the molecular characterization of the translocation breakpoints of 20 ES and PN, showed that most chromosome 22 breakpoints are clustered within a small, 2 kb region. In contrast, the chromosome 11 breakpoints are scattered over a region of at least 40 kb. The translocation leads to the synthesis of chimeric transcript that links sequences from chromosomes 22 and 11. Finally, no evidence was found of any specific difference in the position of ES and PN translocation breakpoints.

Bone Neoplasms↗
PubMed1992

Immunological characterization of avian MAP kinases: evidence for nuclear localization.

The subcellular distribution and regulation of MAP kinase isoforms in chicken hepatoma DU249 cells was investigated with antibodies directed against peptides patterned after sequences in the mitogen-activated protein (MAP) kinases, sea star p44mpk, and rat p44erk1. MonoQ chromatography of cytosol from these cells afforded the resolution of at least four peaks of myelin basic protein (MBP) phosphotransferase activity, but only one of these (peak II) was stimulated in extracts from phorbol ester-treated cells. A 40- to 41-kDa (p41) doublet on Western blots detected with three different MAP kinase antibodies was coincident with peak II, and it probably corresponded to the avian homolog of p42mapk/erk2. Immunofluorescent studies with DU249 cells and chicken embryo fibroblasts revealed that most of the cross-reactive protein with at least two different MAP kinase antibodies was distributed in the nucleus. Subcellular fractionation studies confirmed a predominantly nuclear localization for p41 MAP kinase. Nocodazole arrest of DU249 cells was exploited for the detection of an M-phase-activated MBP kinase that was resolved from p41 MAP kinase by phenyl-Superose chromatography. Western blotting analysis with antibodies for the cdc2-encoded protein kinase and p13suc1-agarose binding studies allowed positive identification of this MBP kinase as p34cdc2.

Amino Acid Sequence↗
PubMed1992

Can "big" insulin-like growth factor II in serum of tumor patients account for the development of extrapancreatic tumor hypoglycemia?

The pathogenesis of extrapancreatic tumor hypoglycemia has been related to the secretion of big insulin-like growth factor (IGF) II by the tumor. In 25 of 28 patients with this type of hypoglycemia we found 1.5-8-fold elevated serum levels of immunoreactive big (15-25 kD), but decreased levels of normal IGF II. After removal of the tumor, big IGF II disappeared and normal IGF II increased. Tumors contained elevated levels of IGF II, 65-80% in the big form. The insulin-like bioactivity of big IGF II and its affinity towards IGF-binding proteins (IGFBP)-2 and -3 are similar to those of normal IGF II, but two- to threefold higher on a molar basis. Big IGF II is mainly bound to the 50-kD IGFBP complex. The latter contains approximately 10 times more of this peptide than in normal serum and displays three- to fourfold increased insulin-like bioactivity. The formation of the 150-kD IGFBP complex with 125I-recombinant human IGFBP-3 is impaired in tumor serum. This results in sequestration of IGFBP-3 and predominant association of big IGF II with IGFBP-2 and -3 in the 50-kD complex. Increased bioavailability of big IGF II in this complex due to unrestricted capillary passage and enhanced insulin bioactivity of this big IGF II pool provide a continuous increased insulin-like potential available to insulin and type 1 IGF receptors of insulin-sensitive tissues and thus may lead to sustained hypoglycemia.

Biological Availability↗
PubMed1992

Isoprenylation of rab proteins on structurally distinct cysteine motifs.

rab proteins are low molecular weight GTP-binding proteins highly related to Ypt1p and Sec4p, which are involved in the control of secretion in yeast Saccharomyces cerevisiae. Morphological and biochemical studies have shown that rab proteins are membrane associated and are localized to specific subcompartments along the exocytic and endocytic pathway. Membrane association requires the presence of C-terminal cysteine residues. The present report indicates that the structurally distinct cysteine motifs of rab proteins are subjected to isoprenylation both in vitro and in vivo. Studies on deletion mutants suggest that an intact C-terminal end is required for the association of rab proteins with the membrane and is necessary for the post-translational modification. Finally, we show that the isoprenoid transferase which modifies rab termini is different from the enzyme which farnesylates nuclear lamins and ras proteins in vitro.

Amino Acid Sequence↗
PubMed1992

Influence of different pressure gradients on late clinical outcome after aortic valve replacement.

Late outcome vs. hemodynamic parameters were assessed and compared in a series of 44 patients followed for 10-17 years after aortic valve replacement either with a Starr-Edwards A 1260 (SE) or a Bjork-Shiley 60 degrees (BS) prosthesis. The two groups, 22 patients each, were selected by computer from the data base SG as to be matched for age, sex, underlying lesion, date of implantation, valve size, left ventricular function, and concomitant coronary artery disease. There was no significant difference in mortality and complication rates. Clinical evaluation at a mean of 12.5 +/- 2.2 years postoperatively revealed identical findings of heart size on chest X-rays (CTR 0.50 +/- 0.04 SE vs. 0.50 +/- 0.05 BS) and nearly identical incidence of left ventricular hypertrophy on the ECG (2/22 SE and 1/22 BS). There was a statistically significant difference in Doppler ultrasonic peak pressure gradients between the two valve types (SE 32 +/- 15 mmHg, BS 23 +/- 9 mmHg; p = 0.047), and of fractional shortening on M-mode echocardiograms (SE 30 +/- 9%, BS 37 +/- 8%, p = 0.038), but this was not reflected by a difference in the symptomatic status of the two groups. It is concluded, that in two groups of patients surviving 10-17 years after isolated aortic valve replacement with SE or BS valves, the statistically significant nine mmHg difference in gradient across the two valve types had no effect on long-term clinical outcome.

Aortic Valve↗
PubMed1991

[Hemodynamics of various heart valve prostheses].

Modern tilting disc and bileaflet prostheses, and bio-prostheses, perform similarly regarding pressure gradients, discharge coefficient and performance index; however, only bio-prostheses increase their opening area with increasing flow. Ball valve prostheses of the Starr-Edwards type perform less satisfactorily with higher pressure gradients and lower performance indices, which may result in less favorable long-term follow-up. Bio-prostheses show degenerative changes with increasing age which, over a period of 7-10 years, can lead to clinically relevant stenoses necessitating reoperation.

Bioprosthesis↗
PubMed1991

Disassembly of in vitro formed lamin head-to-tail polymers by CDC2 kinase.

The nuclear lamina is an intermediate filament-type network underlying the inner nuclear membrane. At the onset of mitosis it depolymerizes, presumably in response to phosphorylation of the lamin proteins. Recently, cdc2 kinase, a major regulator of the eukaryotic cell cycle, was shown to induce lamina depolymerization when incubated with isolated nuclei. Here, we have analysed the structural consequences of lamin phosphorylation by cdc2 kinase using lamin head-to-tail polymers reconstituted in vitro from bacterially expressed chicken lamin B2 protein as a substrate. The effects of phosphorylation were monitored by both a pelleting assay and electron microscopy. We show that lamin B2 head-to-tail polymers disassemble in response to phosphorylation of specific sites that are phosphorylated also during mitosis in vivo. These sites are located within SP/TP motifs N- and C-terminal to the central alpha-helical rod domain of lamin proteins. Subsequent dephosphorylation of these sites by purified phosphatase 1 allows reformation of lamin head-to-tail polymers. The relative importance of N- and C-terminal phosphorylation sites for controlling the assembly state of nuclear lamins was assessed by mutational analysis. Polymers formed of lamin proteins carrying mutations in the C-terminal phosphoacceptor motif could still be disassembled by cdc2 kinase. In contrast, a single point mutation in the N-terminal site (Ser16----Ala) rendered head-to-tail polymers resistant to disassembly. These results emphasize the importance of the N-terminal end domain for lamin head-to-tail polymerization in vitro, and they demonstrate that phosphorylation-dephosphorylation is sufficient to control the longitudinal assembly of lamin B2 dimers.

Adenosine Triphosphate↗
PubMed1991

Ectopic expression of an A-type lamin does not interfere with differentiation of lamin A-negative embryonal carcinoma cells.

The nuclear lamina is an intermediate filament-type network underlying the inner nuclear membrane. It is believed to be important for nuclear envelope integrity and the organization of interphase chromatin. On the basis of biochemical properties and sequence criteria, vertebrate lamin proteins are classified as either A- or B-type. While B-type lamins are expressed in almost all cell types, no A-type lamins are present in early vertebrate embryos or undifferentiated embryonal carcinoma cell lines. Intriguingly, expression of A-type lamins occurs concomitant with cell differentiation and embryonic development. These findings have led to the hypothesis that A-type lamins might play a role in establishing or stabilizing cell-type specific differences in nuclear organization, which in turn might relate to the developmental potential of a cell. To test this hypothesis, we have stably expressed chicken lamin A in undifferentiated murine embryonal carcinoma (P19) cells, and examined the consequences of ectopic lamin A expression for the differentiation state and potential of these cells. Our results demonstrate that the P19 cells, although normally devoid of lamin A, properly incorporate and process chicken lamin A. Moreover, the stably transfected cell lines maintain the properties of undifferentiated cells, demonstrating that expression of lamin A does not directly induce differentiation. Conversely, when exposed to retinoic acid, an inducer of differentiation, lamin A-expressing P19 cells are able to differentiate normally. Taken together, our results suggest that unscheduled expression of A-type lamins is not sufficient to deregulate cell differentiation programs. The implications of these findings for the possible role for lamin A expression during development are discussed.

Animals↗
PubMed1979

Blood conservation during myocardial revascularization.

A prospective study of blood utilization in 50 consecutive patients undergoing elective coronary artery bypass was undertaken. Blood was removed from all patients during induction of anesthesia and reinfused after bypass (mean, 675 ml). Intraoperatively, all discard suction was routed through a regionally heparinized collecting and processing system, and the resulting red cell concentrate was transfused. At the conclusion of bypass, all blood remaining in the pump oxygenator was retained for transfusion. After operation, shed mediastinal blood was collected in a sterile, filtered collection system and transfused. Normovolemic anemia was accepted in hemodynamically stable patients. The mean amount of patients' blood salvaged by the intraoperative system was 259 ml (range, 0 to 724 ml) and by the postoperative system, 194 ml (range, 0 to 564 ml). Ninety-four percent (47/50) of the patients received no bank blood or blood products during their hospital stay. No patients received bank blood intraoperatively or during the first 24 hours following operation. There were no complications attributable to blood salvage techniques.

Adult↗
PubMed1979

Footedness of left- and right-handers.

The performance on a simple tapping task of the hands and feet of left- and right-handers was tested. Right-handers tapped faster with their right hand and right foot. Left-handers tapped faster with their left hand and right foot. Thus, footedness follows handedness in right-handers but not in left-handers. Left-handers showed smaller left/right differences than right-handers in both hand and foot performance. These data are in loose agreement with the modified genetic theory of handedness proposed by Annett (Hand preference and the laterality of cerebral speech, Cortex, 1975).

Adolescent↗
PubMed1975

Thigh emphysema and hip pain secondary to gastrointestinal perforation.

A patient presenting with thigh emphysema and hip pain may suggest intra-abdominal pathology. Three new and 19 previously reported cases of thigh emphysema secondary to bowel disease are reviewed. The thigh and hip manifestations can obscure the primary intra-abdominal process either due to the obvious emphysema or to the obtunded abdominal signs secondary to associated neuropathy. Only one of 22 patients with thigh emphysema secondary to bowel perforation had gas gangrene. Early diagnosis of this clinical association is essential since eight of the 11 deaths occurred within a few days after admission. Right-sided thigh emphysema suggests appendicitis, whereas left-sided emphysema is more likely to be secondary to left colonic diverticulitis or carcinoma.

Appendicitis↗