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G Thomas

Publications and source records attributed to G Thomas.

At least 505 records · Page 28Linked to original sources
PubMed1992

Inhibition or down-regulation of protein kinase C attenuates late phase p70s6k activation induced by epidermal growth factor but not by platelet-derived growth factor or insulin.

The late phase of the time-dependent epidermal growth factor (EGF)-induced biphasic activation of the p70s6k is selectively attenuated by the specific PKC inhibitor, CGP 41,251, a staurosporine derivative. At a 40-fold lower concentration than CGP 41,251, staurosporine inhibits both phases of S6 kinase activation to the same extent, whereas the inactive staurosporine derivative CGP 42,700 shows no effect on either phase. Platelet-derived growth factor (PDGF) and insulin also induce biphasic S6 kinase activation, but in neither case is either phase of activation affected by the presence of CGP 41,251. This finding was unexpected in the case of PDGF, which is a potent activator of PKC and whose receptor directly interacts with phospholipase C gamma 1. However, similar results were obtained following down-regulation of PKC by prolonged 12-O-tetradecanoylphorbol-13-acetate treatment. Therefore, even though EGF and PDGF induce PKC activation, PDGF, unlike EGF, does not appear to use this signaling pathway for late phase p70s6k activation.

3T3 Cells↗
PubMed1992

Identification of guanidino succinate as a putative endogenous source of the endothelium derived relaxing factor.

Using a specific HPLC analysis for guanidines, we find that rat aorta contains guanidino succinate (GS), guanidino acetate (GA), guanidino propionate (GP), guanidino butyrate (GB), methyl guanidine (MG) and guanidine. The concentration of L-arginine (0.05 nmol/mg tissue) is significantly lower than the other guanidines. GS is found to be the most potent vasodilator-guanidine in the rat aorta preparation and this vasodilation depends predominantly on the presence of the endothelium. This effect of GS is antagonized by NG-monomethyl L-arginine (L-NMMA), NW-nitro L-arginine benzyl ester (L-NABA), hemoglobin and by methylene blue, all of which are known to block or attenuate endothelium dependent relaxation. Further, the relaxation mediated by GS is accompanied by the formation of cGMP in the rat aorta. From these results we suggest that GS may be a major endogenous source of EDRF.

Animals↗
PubMed1992

Substrate recognition determinants of the mitogen-activated 70K S6 kinase from rat liver.

The mitogen-activated 70K S6 kinase has an apparent Km for 40 S ribosomal subunits of 0.25 microM. The apparent Km for a synthetic peptide derived from the carboxyl terminus of S6 and containing all of the in vivo sites of phosphorylation was 2.5-fold higher. A number of shorter peptides revealed that the substrate recognition determinants for the preferred site of phosphorylation, Ser236, reside in a seven-amino acid stretch of S6, residues 231-217. Critical to recognition is a block of 3 consecutive arginines, especially Arg231 and Arg233. In contrast, replacement of Ser235 or the preferred site of phosphorylation, Ser236, with alanine has little effect on the apparent Km. Based on this data the consensus recognition sequence would be Arg-(Arg)-Arg-X-X-Ser-X. A number of kinases known to phosphorylate S6, including cAMP-dependent protein kinase and protein kinase C and the 92K S6 kinase II, were also tested for their ability to phosphorylate a decapeptide containing all the critical recognition determinants. Finally, a synthetic peptide containing a putative 70K S6 kinase autoinhibitory domain did not serve as a substrate for the enzyme but did inhibit its activity, although much less effectively than a synthetic peptide containing all the recognition determinants.

Amino Acid Sequence↗
PubMed1992

Allelic loss on chromosome 22 correlates with histopathological predictors of recurrence of meningiomas.

Meningiomas are common tumors of the nervous system. Although usually benign, they may exhibit variable degrees of aggressiveness. Their probability of recurrence after subtotal resection has been correlated with several histological parameters. Independently, a loss of chromosome 22, as evidenced either by cytogenetics or by somatic loss of alleles, has been observed in about half of the cases studied. In 34 meningiomas we have examined the relationship between loss of chromosome 22 alleles and 6 histological predictors of recurrence. Significant correlations were found for 3 of these, i.e. prominent nucleoli (p less than 0.002), microscope count of mitoses (p less than 0.05) and nuclear pleomorphism (p less than 0.02). Correlation with the other 3, i.e. sheeting of cells, vascularity and micronecrosis, did not reach significance. Total tumor score, defined by the sum of the individual scores for these 6 parameters, was strongly correlated to allelic loss (p less than 0.0001). Thus, the loss of chromosome 22 alleles, which possibly contribute to the inactivation of tumor-suppressor gene(s), might be a potent genetic marker of the aggressiveness of meningiomas.

Aneuploidy↗
PubMed1992

Stomal seeding by percutaneous endoscopic gastrostomy in patients with head and neck cancer.

Presented is the first known case of squamous cell carcinoma that developed at the site of a "pull" type percutaneous endoscopic gastrostomy stoma. The patient had advanced squamous cell carcinoma of the pharynx when the percutaneous endoscopic gastrostomy tube was placed. This article should serve as a warning of this potential complication. Alternate techniques and other precautionary methods are described.

Carcinoma, Squamous Cell↗
PubMed1992

Unicolor and bicolor in situ hybridization in the diagnosis of peripheral neuroepithelioma and related tumors.

The chromosome 22 breakpoint of the t(11;22) translocation of peripheral neuroepithelioma has been located, by fluorescence in situ hybridization, in the proximity of the interface between 22q12.1 and 22q12.2. Use of single cosmids or pools of cosmids of the flanking regions enables the monitoring of the translocation in interphase and in metaphase chromosomes. This method can now be routinely applied for the diagnosis of this translocation in mixed round cell tumors.

Bone Neoplasms↗
PubMed1992

Identification and early activation of a Xenopus laevis p70s6k following progesterone-induced meiotic maturation.

Employing oligonucleotide primers derived from the DNA sequence of rat p70s6k a homologous sequence was shown by polymerase chain reaction (PCR) to be present as a maternal transcript in stage IV-VI Xenopus laevis oocytes. The sequence covered 665 bp of p70s6k and was 97% identical at the amino acid level. When used to probe a Northern blot of the poly(A)+ mRNA from stage VI oocytes, this sequence recognized four transcripts of 1.9, 2.5, 3.2 and 5.2 kb. Specific rat p70s6k antibodies immunoprecipitated active S6 kinase from stage VI oocytes but not unfertilized eggs. The basal level of activity was 3- to 5-fold higher in primed versus non-primed oocytes indicating that p70s6k activation was an early event in maturation. Consistent with this observation, progesterone induced a 10-fold activation of the kinase in non-primed oocytes within 1 h post-induction at a time critical for early activation of protein synthesis. A much smaller, variable peak of activation was observed at 85% germinal vesicle breakdown (GVBD), which was dependent on the rate of maturation. Two members of the pp90rsk family, thought to be the sole S6 kinases present in X.laevis oocytes, exhibited distinct kinetics of activation. Finally, the S6 kinase activity present 1 h post-progesterone stimulation was purified and shown to have a Mr of 70K.

3T3 Cells↗
PubMed1992

Influenza virus hemagglutinin with multibasic cleavage site is activated by furin, a subtilisin-like endoprotease.

Many viruses have membrane glycoproteins that are activated at cleavage sites containing multiple arginine and lysine residues by cellular proteases so far not identified. The proteases responsible for cleavage of the hemagglutinin of fowl plague virus, a prototype of these glycoproteins, has now been isolated from Madin-Darby bovine kidney cells. The enzyme has a mol. wt of 85,000, a pH optimum ranging from 6.5 to 7.5, is calcium dependent and recognizes the consensus sequence R-X-K/R-R at the cleavage site of the hemagglutinin. Using a specific antiserum it has been identified as furin, a subtilisin-like eukaryotic protease. The fowl plague virus hemagglutinin was also cleaved after coexpression with human furin from cDNA by vaccinia virus vectors. Peptidyl chloroalkylketones containing the R-X-K/R-R motif specifically bind to the catalytic site of furin and are therefore potent inhibitors of hemagglutinin cleavage and fusion activity.

Affinity Labels↗
PubMed1992

Identification of pulses in hormone time series using outlier detection methods.

The identification of discrete hormonal secretory pulses is of critical importance in clinical endocrinology. Pulses are defined as sudden increases in hormone concentration followed by exponential decay. We propose a model-based iterative procedure for pulse detection in pulsatile hormone time series. Our model is seen to be analogous to the model for innovation outliers in autoregressive series, and outlier detection techniques for pulse identification are adapted to the endocrine context. An original feature of the procedure is that it distinguishes between true pulses and gross observation outliers in the series. Simulation experiments are used to investigate the behaviour of the method under physiologically or clinically relevant circumstances. Five experimental endocrine series from rhesus monkeys, where the times of the pulses are known from the concomitant recording of the electrical activity of the hypothalamus, are analysed.

Animals↗
PubMed1992

In situ hybridization of PCR amplified inter-Alu sequences from a hybrid cell line.

Polymerase chain reaction amplified products promoted by oligonucleotides complementary to the highly repetitive human Alu sequence can be used for in situ hybridization on metaphase chromosomes to investigate the human content of a hybrid cell line. The TC65 primer, which combines the advantages of promoting the amplification of large inter-Alu sequences together with only small flanking Alu sequences, enables a simple and precise characterization to be made, with a high signal to noise ratio. Total human DNA is an efficient competitor in the removal of non-specific signals. The use of this oligonucleotide should be considered in the characterization of the human content of hybrids or in the generation of specific reagents for chromosome decoration.

Animals↗
PubMed1992

Detection by DGGE of a new polymorphism closely linked to the adenomatous polyposis coli region.

The EF5.44 locus is in close proximity to the chromosome 5 region to which the genetic defect responsible for familial adenomatous polyposis has been mapped. We have devised two oligonucleotides that promote the specific polymerase chain reaction (PCR) amplification of a 365-bp sequence in this region. Analysis by denaturing gradient gel electrophoresis of the resulting fragment has unravelled individual differences that could be identified as a single base pair change in a MnlI restriction site. This PCR assayable polymorphism increases the informativeness at this locus, and should be useful in the presymptomatic diagnosis of familial adenomatous polyposis.

Adenomatous Polyposis Coli↗
PubMed1992

Paediatric renal transplantation in Ireland: 1980-1990.

Between 1980 and 1990, 862 renal transplants were performed at our unit. Forty-six of these were given to 38 children. The mean age of the children was 8.6 years. Reflux nephropathy accounted for 39% of the primary renal diseases, followed by congenital disorders (30%), and glomerulonephritis (16%). Seventy percent of the grafts were from cadaveric donors. The one year patient survival was 90%, and the one year graft survival 61%. Seven children received a second graft with a one year graft survival of 71%.

Adolescent↗
PubMed1992

New-onset ventricular tachycardia during pregnancy.

During evaluation for palpitations, presyncope, or syncope, seven pregnant women had documented ventricular tachycardia. Before pregnancy none had a history of significant cardiac disease or symptomatic arrhythmia. The tachycardia rate ranged from 117 to 250 beats/min and lasted up to 65 seconds. Arrhythmia evaluation in five of the patients suggested catecholamine-sensitive ventricular tachycardia. This diagnosis was supported by either a positive relation to exercise or isoproterenol infusion, suppression of arrhythmia by beta-blockade or sleep, and lack of induction of arrhythmia by programmed electrical stimulation of the heart. The arrhythmias resolved in one patient soon after evaluation and in one other patient after 2 months of controlling therapy. Five other patients continued to receive therapy throughout pregnancy. Delivery was accomplished in all patients without significant maternal or neonatal complications.

Echocardiography↗
PubMed1992

Groin dissection versus groin radiation in carcinoma of the vulva: a Gynecologic Oncology Group study.

PURPOSE: The objective of this study was to determine if groin radiation was superior to and less morbid than groin dissection. METHODS AND MATERIALS: Members of the Gynecologic Oncology Group randomized 58 patients with squamous carcinoma of the vulva and nonsuspicious (N0-1) inguinal nodes to receive either groin dissection or groin radiation, each in conjunction with radical vulvectomy. Radiation therapy consisted of a dose of 50 Gray given in daily 200 centiGray fractions to a depth of 3 cm below the anterior skin surface. RESULTS: The study was closed prematurely when interim monitoring revealed an excessive number of groin relapses on the groin radiation regimen. Metastatic involvement of the groin nodes was projected to occur in 24% of patients based on this Group's previous experience. On the groin dissection regimen, there were 5/25 (20.0%) patients with positive groin nodes. These patients received post-operative radiation. There were five groin relapses among the 27 (18.5%) patients on the groin radiation regimen and none on the groin dissection regimen. The groin dissection regimen had significantly better progression-free interval (p = 0.03) and survival (p = 0.04). CONCLUSION: Radiation of the intact groins as given in this study is significantly inferior to groin dissection in patients with squamous carcinoma of the vulva and N0-1 nodes.

Adult↗