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S Thomas

Publications and source records attributed to S Thomas.

At least 19 recordsLinked to original sources
PubMed1992

Association of the Shc and Grb2/Sem5 SH2-containing proteins is implicated in activation of the Ras pathway by tyrosine kinases.

The mammalian shc gene encodes two overlapping, widely expressed proteins of 46 and 52K, with a carboxy-terminal SH2 domain that binds activated growth factor receptors, and a more amino-terminal glycine/proline-rich region. These shc gene products (Shc) are transforming when overexpressed in fibroblasts. Shc proteins become phosphorylated on tyrosine in cells stimulated with a variety of growth factors, and in cells transformed by v-src (ref. 2), suggesting that they are tyrosine kinase targets that control a mitogenic signalling pathway. Here we report that tyrosine-phosphorylated Shc proteins form a specific complex with a non-phosphorylated 23K polypeptide encoded by the grb2/sem-5 gene. The grb2/sem-5 gene product itself contains an SH2 domain, which mediates binding to Shc, and is implicated in activation of the Ras guanine nucleotide-binding protein by tyrosine kinases in both Caenorhabditis elegans and mammalian cells. Consistent with a role in signalling through Ras, shc overexpression induced Ras-dependent neurite outgrowth in PC12 cells. These results suggest that Shc tyrosine phosphorylation can couple tyrosine kinases to Grb2/Sem-5, through formation of a Shc-Grb2/Sem-5 complex, and thereby regulate the mammalian Ras signalling pathway.

Adaptor Proteins, Signal Transducing↗
PubMed1992

Intra-oral carcinoma simulating benign oral disease.

Intra-oral carcinoma can present in a variety of ways. Whilst carcinoma classically presents as an irregular, indurated, painless mass or ulcer, it is also recognised as being a great 'mimic' of benign lesions. A series of four cases of intra-oral squamous cell carcinoma is presented in which the initial presentation suggested a lesion of benign or dental origin. Factors which raise the index of suspicion are discussed.

Aged↗
PubMed1992

Roles of structural domains in the morphology and surface anchoring of the tetragonal paracrystalline array of Aeromonas hydrophila. Biochemical characterization of the major structural domain.

The tetragonally arranged S-layer of Aeromonas hydrophila contains two morphological domains. The mature S-layer protein of A. hydrophila has a subunit molecular weight of 52,000, and has been reported to contain two structural domains. Here a mutant has been isolated which produces an S-layer of subunit molecular weight 38,650 as determined by sedimentation analysis. This truncated S-protein was exported via the periplasm to the cell surface, but could not self-assemble into a tetragonal array or be anchored to the cell surface. Instead the truncated protein formed cup-like structures which were purified and characterized biochemically. Automated Edman degradation showed that the truncated protein comprised the amino-terminal structural domain of the S-protein. This domain had an increased hydrophobic amino acid content relative to the wild-type protein, and contained approximately 42% beta-sheet, 10% alpha-helix, and 19% beta-turn. Differences in alpha-helix and beta-turn contents between the wild-type and truncated proteins were observed when the effects of pH and SDS were examined, indicating that the carboxy terminus influences the effects of environmental change on the conformation of the S-protein. This lesser carboxy-terminal array also appears to be required for both correct array morphology, and array anchoring, while the greater amino-terminal domain appears to comprise the major morphological core of the surface array.

Aeromonas hydrophila↗
PubMed1992

Role of protein kinase C in induction of gene expression and inhibition of cell proliferation by interferon alpha.

Recent studies have suggested that protein kinase C (PKC) may be involved in the mechanism of signal transduction by which members of the interferon (IFN) family regulate gene expression and cell phenotype. We have investigated the role of PKC in the control of cell growth and gene expression by IFN alpha in Daudi cells. Treatment of these cells with two analogues of staurosporine, which are potent inhibitors of PKC, completely blocked the induction by IFN alpha of the mRNA for 2',5'-oligoadenylate synthetase and the 6-16 gene. These compounds also inhibited cell proliferation and thymidine incorporation in this system. In contrast, the protein kinase inhibitor 1-(5-isoquinolinylsulphonyl)-2-methylpiperazine (H7) did not significantly inhibit the induction of these genes by IFN alpha and had no effect on Daudi cell growth or thymidine incorporation in the presence or absence of IFN alpha. No effect of IFN alpha on total PKC activity could be observed, and there were no significant changes in the overall levels of individual PKC isoforms or their mRNA following IFN alpha treatment. In contrast, treatment of Daudi cells with the phorbol ester 12-O-tetradecanoylphorbol 13-acetate, which also inhibits cell proliferation, strongly down-regulated PKC. These data suggest that the activity of a PKC species, or a closely related enzyme, may be required both for continued cell proliferation and the response to IFN alpha in Daudi cells, but that IFN-induced growth inhibition does not involve overall down-regulation or change in activity of PKC.

Amino Acid Sequence↗
PubMed1992

Control and consequences of adrenergic activation of red blood cell Na+/H+ exchange on blood oxygen and carbon dioxide transport in fish.

The catecholamines, adrenaline and noradrenaline, are released into the circulation of fish during a variety of physical and environmental disturbances that share the common feature of a requirement for enhanced blood oxygen transport. Indeed, the dominant factor controlling the mobilization of catecholamines from chromaffin tissue is a depression of blood oxygen content usually coinciding with a reduction of hemoglobin-O2 (Hb-O2) binding to 50-60% saturation. The elevation of plasma catecholamine levels, under such conditions, activates a beta-adrenergic cyclic AMP-dependent Na+/H+ exchanger on the red blood cell (rbc) membrane. The adrenergic responsiveness AMP-dependent Na+/H+ exchanger on the red blood cell (rbc) membrane. The adrenergic responsiveness of the rbc Na+/H+ exchanger to catecholamines varies both within and between species. Such inter- and intra-specific differences may reflect, in part, the availability of cell surface beta-adrenoceptors that are functionally coupled to adenylate cyclase. The activation of rbc Na+/H+ exchange and the accompanying profound adjustments of intracellular and extracellular acid-base status, nucleoside triphosphate (NTP) levels, and cooperativity of Hb-O2 binding have important consequences on both O2 and CO2 transfer and transport in the blood that vary markedly at the sites of oxygenation (the gill) and deoxygenation (the tissues) thereby enabling simultaneous amelioration of O2 loading and unloading. At the gill, oxygen transfer is enhanced owing to increases in Hb-O2 affinity and capacity while at the tissues, oxygen delivery is facilitated by a reduction of Hb-O2 affinity. This reduction in affinity at the tissues is a consequence of the combined effects of increased cooperativity of Hb-O2 binding and a rise in venous PCO2 (PvCO2) caused by the titration of HCO3- by H+ extruded by the rbc Na+/H+ exchanger. This elevation of PvCO2 may contribute to the rise in arterial PCO2 (PaCO2) observed after adrenergic activation of rbc Na+/H+ exchange that is caused primarily by impairment of rbc CO2 excretion related to modification of the intracellular acid-base status.

Animals↗
PubMed1992

Clinical value of polysomnography.

Polysomnography is used increasingly to investigate patients with possible sleep apnoea/hypopnoea syndrome (SAHS), but it has not been assessed critically. We thus examined prospectively the value of electrophysiological and respiratory monitoring in 200 consecutive adults (163 men, 37 women; mean [SD] age 50 [13] years) having polysomnography. At polysomnography, 91 patients had SAHS (greater than 15 apnoeas + hypopnoeas [A + H] per h asleep) and 11 had periodic limb-movement disorder. Recording sleep electrophysiologically was of no diagnostic value and SAHS could be as accurately defined by A + H per time in bed as by A + H per time asleep. 66% of patients with SAHS could be diagnosed with oximetry alone, but many of the undiagnosed patients had moderately severe SAHS and benefited from treatment. Neurophysiological sleep recording is unnecessary and oximetry alone is of limited value in the overnight investigation of patients suspected of having SAHS.

Electroencephalography↗
PubMed1992

Metabolic alkalosis and the response of the trout, Salmo fario, to acute severe hypoxia.

Trout (Salmo fario) were acutely transferred from seawater to freshwater in order to induce blood metabolic alkalosis (cf. Maxime et al., J. Comp. Physiol. 160: 31-39, 1990). After 2 weeks, the fish were exposed to severe environmental hypoxia (final water oxygen partial pressure, PWO2 = 25-45 Torr, reached within 20 min), to assess the impact of the experimentally induced alkalosis, and hence increased haemoglobin-oxygen (Hb-O2) affinity, on various aspects of the hypoxic response. This was accomplished by monitoring oxygen partial pressure and total oxygen content of arterial blood (PaO2 and CaO2), extracellular pH (pHe), red blood cell (RBC) intracellular pH (pHi), and the concentrations of plasma adrenaline, noradrenaline, lactate and haemoglobin (Hb) at 5 min intervals. Blood from normoxic fish exhibited high pHe and RBC pHi values (8.32 +/- 0.02 and 7.53 +/- 0.03, respectively). During hypoxia PaO2 declined to 10 Torr within 25 min; the first 5 min provoked increases of pHe and pHi to 8.43 +/- 0.03 and 7.71 +/- 0.03, respectively; thereafter, pHe decreased whilst pHi remained elevated. The blood lactate concentration increased from 2.30 +/- 0.76 mmol.L-1 in normoxia to 14.94 +/- 5.7 mmol.L-1 at the conclusion (60 min) of the hypoxic exposure and catecholamine levels also increased progressively (from 2.94 +/- 0.51 and 1.90 +/- 0.50 nmol.L-1, in normoxia, to 191.91 +/- 64.25 and 72.00 +/- 25.02 nmol.L-1, at their highest levels, for adrenaline and noradrenaline, respectively). Determination of the PaO2 thresholds for lactate and catecholamine release demonstrated that these substances appeared in the bloodstream when the degree of O2 saturation of the haemoglobin fell below 60%. The results demonstrate that initial blood alkalosis does not prevent the typical physiological responses of trout to hypoxia but simply shifts to lower PaO2 values the threshold at which these responses begin.

Acid-Base Equilibrium↗
PubMed1992

Isolation and purification of extracellular matrix vesicles from blood vessels.

Extracellular membrane-bound vesicles (called matrix vesicles) which occur in abundance in atherosclerotic blood vessels are believed to be associated with lipid accumulation and calcification. A technique has been developed to isolate them from experimental aneurysms in sheep in which they are known to be plentiful. The matrix vesicles were isolated by differential centrifugation following extraction by hypotonic salt solution. Most of the vesicles were pelleted at 30,000g and fell within the size range of matrix vesicles in situ in the aneurysmal wall. Preliminary characterization of the enzymatic activities indicates that many of these vesicles are formed from cell membranes rather than being derived from lysosomes, mitochondria or endoplasmic reticulum. Morphologically they are similar to matrix vesicles of other mineralizing tissues.

Animals↗
PubMed1992

A comprehensive study of genic variation in natural populations of Drosophila melanogaster. VII. Varying rates of genic divergence as revealed by two-dimensional electrophoresis.

Four sibling species from the melanogaster subgroup (Drosophila melanogaster, D. simulans, D. sechellia, and D. mauritiana) were studied for genetic divergence, by high-resolution two-dimensional protein electrophoresis (2DE) coupled with ultrasensitive silver staining. A total of eight tissues from larval and adult developmental stages representing both gonadal (germ-line) and nongonadal (somatic) tissues were analyzed for protein divergence between species. Close to 400 polypeptides (protein spots) were scored from each tissue and species, and protein divergence was measured on the basis of qualitative differences (presence/absence) of protein spots in pairwise species comparisons. The observed levels of genic divergence varied among tissues and among species. When larval hemolymph proteins (which are known to be highly polymorphic) were excluded, there was no evidence to suggest that either the larval or adult-stage proteins, as a whole, are more diverged than the other; variation between different tissues rather than between developmental stages appears to be the most significant factor affecting genetic divergence between species. The reproductive tissue (testis and accessory gland) showed more divergence than did the nonreproductive tissue; D. melanogaster testis (from both larvae and adult males) showed the highest level of divergence. In view of the previous observation that D. simulans, D. mauritiana, and D. sechellia show similar but significantly less reproductive isolation from each other than from D. melanogaster, the present results suggest a correlation between the levels of reproductive-tract-protein divergence and the degree of reproductive isolation in these species.

Animals↗
PubMed1992

Alterations in oropharyngeal flora in patients with a nasogastric tube: a cohort study.

OBJECTIVE: To determine whether or not the presence of a nasogastric tube causes a change in the bacterial flora in the oropharynx. STUDY DESIGN: Cohort (prospective) design with concurrent control. SETTING: General Surgical and Ear, Nose, and Throat Units of a tertiary care hospital. PATIENTS: Sixteen patients with and 14 patients without a nasogastric tube. INTERVENTIONS: Patients scheduled to undergo surgery under general anesthesia with endotracheal intubation were eligible for inclusion in the study. From these patients, a study cohort of 16 consecutive patients who were to have nasogastric tube intubation and 14 patients who were not to have nasogastric intubation were enrolled. All patients had a high oropharyngeal swab taken for bacteriologic culture just before surgery. The swab of the oropharynx for culture was repeated after 48 to 72 hrs. The type of organism grown was identified and compared between and within the two groups. RESULTS: There was a significant increase in the frequency of colonization of the oropharynx by pathogenic Gram-negative bacteria after 48 to 72 hrs of nasogastric intubation in comparison with the preintubation level (p < .01) as well as in comparison with the group that did not have nasogastric intubation (p < .001). The pathogens included Pseudomonas, Klebsiella, Proteus and Escherichia coli. There was also a tendency for suppression of normal flora. There was no significant change in the flora of the control group of patients who did not have nasogastric intubation. The two groups were comparable with respect to age, gender, severity of underlying illness, and use of prophylactic perioperative antibiotics. CONCLUSIONS: The presence of nasogastric tubes in patients predisposes to colonization by Gram-negative pathogenic bacteria within 48 to 72 hrs.

Adult↗
PubMed1992

Human papillomaviruses in normal oral mucosa: a comparison of methods for sample collection.

The prevalence of six genital genotypes of HPV was assessed in the clinically normal oral mucosa of an adult Caucasian population, and three methods of sample collection compared. HPV DNA was detected in the mouth of 60% of 60 subjects. HPV 16 was the most prevalent genotype, and positive samples were found most frequently in men over 50. A 3% sucrose mouthwash produced more positive results (51%) than mucosal scrapes of three separate sites (45%) or buccal mucosal biopsies (12%). There was no association of a positive result for HPV DNA with any particular mucosal site. A mouthwash was the preferred single screening method for epidemiologic studies of HPV DNA in the mouth, but the greatest yield of positive samples was obtained if multiple sampling techniques were employed.

Adolescent↗
PubMed1992

Potential markers of heavy training in highly trained distance runners.

Markers of a heavy increase in training were examined in ten highly trained distance runners (mean(s.d.) age 29.8(1.7) years, maximal oxygen intake 65.3 ml kg-1 min-1, personal best 10-km time 31 min 4 s) who undertook a deliberate 38% increment of training over a 3-week period. Their running performance did not improve, and six of the ten subjects developed sustained fatigue, suggesting that training was excessive, although the full clinical picture of overtraining did not develop. The Profile of Mood States was the best single marker of disturbed function, indicating increased fatigue and decreased vigour. There were no useful changes of resting heart rate or perceived exertion during submaximal running, sleep was undisturbed, and there were no orthopaedic injuries. Two subjects developed rhinoviral infections following the heavy training, and a third complained of symptoms that were diagnosed 2 weeks later as exercise-induced asthma. The increase of serum cortisol normally induced by 30 min of submaximal exercise was no longer seen when the same acute exercise was performed after heavy training. Resting lymphocyte proliferation tended to increase in response to phytohaematoglutinin (PHA) and concanavalin A (Con A), the ratio of helper to suppressor cells (H/S) decreased, and pokeweed mitogen induced smaller increases in IgG and IgM synthesis. Whereas before heavy training, PHA-stimulated lymphocyte proliferation was unchanged by 30 min of acute submaximal exercise, after 3 weeks of heavy training the same bout of exercise caused an 18% suppression of proliferation. Likewise, heavy training brought about a decrease of T-lymphocytes in response to acute submaximal exercise, but an abolition of the acute exercise-induced decrease in the H/S ratio. The previously observed exercise-induced decrease of IgG synthesis did not occur when the same acute bout of exercise was performed after heavy training. We conclude that such minor and transient changes of immune function may possibly be a warning that training is becoming excessive, but they have only a limited significance for overall immune function.

Adult↗
PubMed1992

Leftward shift of R-axis on electrocardiogram in patients with panic disorder and depression.

In a prospective study, we have compared R-axis on routine electrocardiograms of panic disorder patients (n = 52) with that of depressed patients (n = 41) and normal controls (n = 65). All subjects were physically healthy and were normotensive. There was a significant leftward shift of R-axis in both depressed and panic disorder patients compared to normal controls. The implications of these findings are discussed.

Adult↗