Search PubMed⌕ Search

Biomedical subjects

C Davis

Publications and source records attributed to C Davis.

At least 181 records · Page 10Linked to original sources
PubMed1995

Characterization of a life-cycle-stage-regulated membrane protein tyrosine phosphatase in Trypanosoma brucei.

We report the first characterization of plasma-membrane-bound tyrosine phosphatase activity in the haemoprotozoan. Trypanosoma brucei. Several enzymic properties of the membrane fraction were identical to other protein tyrosine phosphatases (PTPases), such as (a) insensitivity to inhibitors of other protein phosphatases, including tetramisole, sodium tartrate and okadaic acid, (b) inhibition by sodium vanadate, and (c) activation by spermidine. Additionally, T. brucei PTPase activity presented two novel features, an acidic pH optimum at pH 4.0-5.0 and a very low Km value (2.5 nM) for the specific synthetic substrate, Tyr(P)Raytide. Higher Km values of 170 nM for Tyr(P)-RCML (RCML, reduced, carboxamidomethylated and maleylated lysozyme) and of 3 mM for the non-specific inorganic substrate p-nitrophenyl phosphate, suggested that the PTPase activity of T. brucei was substrate specific. Reconstitution experiments on bloodstream-stage membrane proteins revealed that three polypeptides of 148, 115 and 72 kDa contained vanadate-inhibitable PTPase activity. Modulator assays revealed that the 72-kDa protein was responsible for the observed spermidine stimulation, but indicated that the modulator profile of the 148-kDa protein was most similar to the whole membrane fraction. Furthermore, the PTPase activity of T. brucei was life-cycle-stage regulated. Neither the whole membrane fraction nor the reconstituted proteins of the procyclic insect stage dephosphorylated tyrosine residues.

Animals↗
PubMed1995

Macromolecular arrangement in the aminoacyl-tRNA.elongation factor Tu.GTP ternary complex. A fluorescence energy transfer study.

The distance between the corner of the L-shaped transfer RNA and the GTP bound to elongation factor Tu (EF-Tu) in the aminoacyl-tRNA.EF-Tu.GTP ternary complex was measured using fluorescence energy transfer. The donor dye, fluorescein (Fl), was attached covalently to the 4-thiouridine base at position 8 of tRNAPhe, and aminoacylation yielded Phe-tRNAPhe-Fl8. The ribose of GTP was covalently modified at the 2'(3') position with the acceptor dye rhodamine (Rh) to form GTP-Rh. Formation of the Phe-tRNAPhe-Fl8.EF-Tu.GTP-Rh ternary complex was verified both by EF-Tu protection of the aminoacyl bond from chemical hydrolysis and by an EF-Tu.GTP-dependent increase in fluorescein intensity. Spectral analyses revealed that both the emission intensity and lifetime of fluorescein were greater in the Phe-tRNAPhe-Fl8.EF-Tu.GTP ternary complex than in the Phe-tRNAPhe-Fl8.EF-Tu.GTP-Rh ternary complex. These spectral differences disappeared when excess GTP was added to replace GTP-Rh in the latter ternary complex, thereby showing that excited-state energy was transferred from fluorescein to rhodamine in the ternary complex. The efficiency of singlet-singlet energy transfer was low (10-12%), corresponding to a distance between the donor and acceptor dyes in the ternary complex of 70 +/- 7 A, where the indicated uncertainty reflects the uncertainty in dye orientation. After correction for the lengths of the probe attachment tethers, the 2'(3')-oxygen of the GTP ribose and the sulfur in the s4U are separated by a minimum of 49 A. This large distance limits the possible arrangements of the EF-Tu and the tRNA in the ternary complex.(ABSTRACT TRUNCATED AT 250 WORDS)

Energy Transfer↗
PubMed1995

Relationship between evoked potentials and clinical status in spinal cord ischemia.

STUDY DESIGN AND METHODS: Sciatic neurogenic motor-evoked potentials, spinal evoked potentials, and somatosensory-evoked potentials were recorded in 12 anesthetized dogs that had arterial ischemia of the lumbar cord produced by ligation of segmental arteries. The presence or absence of the above-mentioned potentials was compared with the clinical status of repeated wake-up tests. RESULTS: Although these results were complicated, sciatic neurogenic motor-evoked potential was more sensitive to the spinal cord ischemia and was a better predictor of clinical outcome than spinal evoked potential and somatosensory-evoked potential. However, the presence was not a guarantee of normal function. The initial morphologic change of these potentials secondary to ischemia consisted of a decrease in amplitude and in the number of peaks without a shift of latency. CONCLUSIONS: The present study suggests that the peripheral neurogenic motor-evoked potential is a better warning system for spinal cord ischemia and that its adoption may contribute to the prevention of cord ischemia during spinal surgery, whereas somatosensory-evoked potential and spinal evoked potential cannot be indices.

Animals↗
PubMed1995

Trypanosoma brucei and Trypanosoma cruzi: life cycle-regulated protein tyrosine phosphatase activity.

Recent evidence that Trypanosoma brucei synthesizes stage-regulated phosphotyrosine containing proteins and protein kinases stimulated us to assay bloodstream and insect stages of Trypanosoma cruzi and both pleomorphic and monomorphic clones of T. brucei for tyrosine phosphatase activity. Bloodstream and procyclic insect stages of T. brucei contained a 55-kDa protein that cross-reacted with monoclonal antibodies directed against the human placental tyrosine phosphatase PTP1B. Protein lysates of all life cycle stages of both trypanosomes dephosphorylated a nonspecific substrate, pNPP, and the specific substrate Tyr(P)Raytide. Dephosphorylation of Tyr(P)Raytide was effectively inhibited only by sodium vanadate, a specific phosphotyrosine phosphatase inhibitor, but pNPP activity was also inhibited by sodium fluoride (NaF) in lysates of T. brucei and by NaF and sodium tartrate in lysates of T. cruzi, suggesting that their respective lysates also contained serine/threonine and acid phosphatase activities. Fractionation studies revealed that most of this activity was in the cytosol. Stage regulation of tyrosine phosphatase activity in T. cruzi was strongly suggested by differences in the optimal pH for tyrosine phosphatase activity (7.0 for amastigotes and epimastigotes; 5.0 for trypomastigotes). We conclude that both species of trypanosomes synthesize tyrosine phosphatases and propose that identification and characterization of the enzymes responsible for this phosphatase activity could provide information about trypanosomal virulence or the regulation of trypanosomal growth and differentiation.

Animals↗
PubMed1995

Obsessive compulsiveness and physical activity in anorexia nervosa and high-level exercising.

Although excessive physical activity and obsessive compulsiveness are both prevalent in anorexia nervosa (AN), to date, the association between these two factors has not been systematically investigated. The aim of the present study was to investigate the relationship between obsessive compulsiveness and both behavioral and psychological aspects of exercise in women with AN, and to compare them to a nonclinical sample of females classified as either moderate or high-level exercisers. Results indicated that obsessive compulsiveness, weight preoccupation, and pathological aspects of exercise were significantly related to the level of physical activity among the eating disorder patients. For the high-level exercisers, only obsessive compulsiveness was significantly related to the amount of physical activity. The findings are discussed in terms of a model in which physical activity, starvation, and obsessive compulsiveness are reciprocally and dynamically related, with each factor creating a destructive bidirectional loop that is resistant to change and difficult to break. We propose that this self-perpetuating loop may be a significant influence in the development and maintenance of eating disorders in a certain subgroup of women.

Adult↗
PubMed1995

Activation of protein kinase C by the capsaicin analogue resiniferatoxin in sensory neurones.

Resiniferatoxin and capsaicin are sensory neurone-specific excitotoxins that operate a common cation channel in nociceptors. Resiniferatoxin is structurally similar to capsaicin and to phorbol esters. Specific [3H]-resiniferatoxin binding, which was detected in the membrane (KD value 1.8 +/- 0.2 nM) but not cytosolic fraction of rat dorsal root ganglia, could not be displaced by phorbol 12,13-dibutyrate. Conversely, resiniferatoxin did not displace [3H]phorbol 12,13-dibutyrate binding in either the cytosolic or membrane fraction. Resiniferatoxin and capsaicin both caused translocation of protein kinase C in dorsal root ganglion neurones (EC50 value 18 +/- 3 nM). This translocation was greatly reduced but not abolished, in the absence of external Ca2+, suggesting that it was secondary to Ca2+ entry. Resiniferatoxin also caused direct activation of a Ca(2+)- and lipid-dependent kinase (or kinases) in the cytosolic fraction of dorsal root ganglia, at concentrations (100 nM to 10 microM) higher than required for displacement of [3H]resiniferatoxin binding or translocation of protein kinase C. Capsaicin (up to 10 microM) was unable to mimic this effect. These data imply that although resiniferatoxin-induced translocation of protein kinase C in dorsal root ganglion neurones was mainly indirect, it also caused direct activation of a protein kinase C-like kinase in these cells.

Animals↗
PubMed1995

Surgical and non-surgical treatment of symptomatic intracranial meningiomas.

The results of treatment of intracranial symptomatic meningiomas from a personal consecutive series are presented. Thirty-three patients were retrospectively reviewed following surgical treatment and 11 patients were treated prospectively with gestrinone, a synthetic antiprogesterone drug. Comparative results suggest that research and future advances in treatment will be non-surgical. The time has come for neurosurgeons to recognize this reality.

Adult↗
PubMed1995

Fluoxetine is ineffective for treatment of cocaine dependence or concurrent opiate and cocaine dependence: two placebo-controlled double-blind trials.

Cocaine dependence has proved difficult to treat, whether occurring alone or in combination with opiate dependence. No medication has been demonstrated to be uniquely effective. Fluoxetine was examined as a candidate in two randomized, double-blind, placebo-controlled trials, one with cocaine-dependent patients (study 1) and the other with patients both cocaine and opiate dependent (study 2). It was selected for known specific action, antidepressant effects, minimum side effects, and data showing reduced cocaine effect and self-administration. Clinic visit frequency requirement, a variable with implications for treatment and cost, was also examined in study 1. A total of 228 patients in study 1 and 21 patients in study 2 completed consent and intake procedures. Patients with serious medical or DSM-III-R diagnoses other than cocaine dependence (study 1) or opiate and cocaine dependence (study 2) were excluded. Study 1 patients were assigned to one of two visit frequency schedules (2 or 5 days/week) and one of three medication doses (0, 20, or 40 mg of fluoxetine/day). Study 2 patients received placebo or 20 mg of fluoxetine and 65 to 80 mg of methadone and attended the clinic 5 days/week. All patients participated in individual therapy sessions. Urine screens were conducted twice weekly. A fluoxetine dose response relationship emerged in study 1 for retention with groups from best to worst being placebo, 20 mg, and 40 mg. Dose effect order was the same for both visit conditions. Cocaine use persisted in all groups. The two visits/week condition was correlated with better retention than the five visits/week condition. A significant interaction emerged between intake urine and visit frequency; patients with benzoylecognine screens at intake used cocaine significantly less in the 5 days/week condition, while exhibiting no reduction in the 2 days/week condition. Patients cocaine positive at intake were better retained with infrequent visits. In study 2, a transient reduction in benzoylecognine-positive drug screens emerged for the fluoxetine group. These complementary studies demonstrate that fluoxetine is ineffective in reducing cocaine use or craving. Study 1 also points to setting conditions modulating treatment outcome.

Adult↗
PubMed1995

The role of personality factors in the reporting of side effect complaints to moclobemide and placebo: a study of healthy male and female volunteers.

Although there is good evidence of a relationship between certain personality factors (viz. neuroticism and hypochondriasis) in the reporting of somatic symptoms-both in clinical and in nonclinical research-the recognition of the moderating role of individual differences in the frequency and intensity of side effect reporting is virtually absent from drug trial research. This study was a double-blind moclobemide-versus-placebo trial, the purpose of which was twofold: to investigate the degree of side effect complaints in a sample of healthy nonclinical men and women and to assess the role of personality in symptom reporting. Although there was no overall difference between the groups with respect to side effect complaints, there was a highly significant neuroticism x group x time interaction. In both groups, we found the expected positive relationship between neuroticism and symptom reporting at baseline. At the end of the study, however, this relationship was close to zero in the moclobemide group and had increased to close to 0.60 in the placebo group. These results were essentially replicated when neuroticism was substituted in the regression model by a psychometric measure of hypochondriasis. Our findings provide a striking demonstration of the role of personality factors in the placebo adverse response. As well, they indicate that adverse reactions to the medication were also linked to personality differences. Taken together, our results underscore the importance of considering individual differences in all aspects of pharmacologic research that involve subjective interpretation on the part of patients and subjects.

Adolescent↗
PubMed1995

AFR1 promotes polarized apical morphogenesis in Saccharomyces cerevisiae.

The G protein-coupled alpha-factor receptor promotes polarized growth toward a mating partner. alpha-Factor induces the expression of AFR1, which acts together with the receptor C terminus to promote normal morphogenesis. The function of AFR1 was investigated by engineering cells to constitutively express AFR1 without alpha-factor. Constitutive AFR1 expression caused cells to form elongated buds that demonstrate that AFR1 can also interact with the morphogenesis components that promote bud formation. A similar elongated bud phenotype is caused by mutation of the CDC3, CDC10, CDC11, and CDC12 genes, which encode putative filament proteins that form a ring at the bud neck. AFR1 may act directly on the filament proteins, since immunolocalization detected AFR1 at the bud neck and interaction of AFR1 and CDC12 was detected in the two-hybrid protein assay. AFR1 localized to the base of pheromone-induced projections. These results suggest that AFR1 and the putative filament proteins act together with the receptor to facilitate proper localization of components during mating.

Blotting, Western↗
PubMed1995

Role of ECMO in the treatment of respiratory syncytial virus bronchiolitis: a collaborative report.

AIM: To report the collaborative experience of extracorporeal membrane oxygenation (ECMO) in the treatment of respiratory syncytial virus (RSV) bronchiolitis between April 1989 and January 1995. METHODS: The medical records of patients with confirmed RSV bronchiolitis referred to three centres (Leicester, Glasgow, and Great Ormond Street) were reviewed. RESULTS: Twenty four infants were identified. Seventeen had been born prematurely (gestational range 23-40 weeks, median 30 weeks). Thirteen infants had been mechanically ventilated after birth and seven of these had evidence of bronchopulmonary dysplasia (BPD). The age of onset of RSV infection varied from three to 64 weeks (mean 17.4 weeks, median 12 weeks). Ventilation before ECMO ranged from one to 16 days and oxygenation indices at the time of referral ranged from 21-73 (mean 39). Ribavirin was used in eight of the 24 patients. Sixteen patients received venoarterial and eight veno-venous ECMO. ECMO hours ranged from 32-647 (median 196 hours). One infant died (survival rate 96%). Cranial ultrasound abnormalities were detected in three patients. However, at follow up only one of the 23 survivors had evidence of developmental delay. CONCLUSION: A group of paediatric patients in whom ECMO can be of benefit has been identified. The use of ECMO should be considered when other means of support prove unsuccessful.

Age of Onset↗
PubMed1995

Physician counseling for smoking cessation: is the glass half empty?

BACKGROUND: Professional groups urge physicians to aggressively counsel their patients who smoke, but research evaluating the effectiveness of physician counseling has produced mixed results. METHODS: Four hundred ten smokers identified in a previous study were contacted 1 year later to determine whether they had quit smoking. In both studies, smokers were asked whether their physicians had counseled them in any of six specific ways (eg, advising the patient of personal health risks and the need to stop smoking, or discussing cessation methods). RESULTS: Seventy-nine percent of patients reported that their physician counseled them either at the initial visit or at some time during the following year; 42% reported having tried to quit at least once during the year, but only 5.9% were nonsmokers at 1-year follow-up. Physician counseling had no effect on the rate of successful attempts to quit. Patients with serious health problems were more likely to be counseled and to attempt to quit (P < .02). Non-Hispanic white patients were more likely to be counseled but less likely to attempt to quit (P < .01). CONCLUSIONS: Counseling by physicians appears to motivate some patients to attempt to quit, but this study did not show significant improvement in actual quit rates in patients who were counseled by a physician.

Adolescent↗