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J Thomas

Publications and source records attributed to J Thomas.

At least 397 records · Page 22Linked to original sources
PubMed1993

Expression in Escherichia coli of the cloned flavin-containing monooxygenase from pig liver.

The amino acid sequence of pig liver flavin-containing monooxygenase (PgLFMO) was determined by nucleotide analysis of cDNA clones isolated using synthetic oligonucleotide probes. Most of the clones isolated were missing the 5'-noncoding region and the first seven codons including the putative initiation codon ATG. A full-length cDNA clone, PgLFMO1, was obtained by extending the 5'-end sequence to include an ATG initiation codon and the codons corresponding to the 5'-end using the polymerase chain reaction. Restriction sites for EcoRI and SalI were incorporated at the 5'- and 3'-ends of the cDNA, respectively, by polymerase chain reaction to provide a full-length cDNA clone, pTrcPgLFMO1. Escherichia coli strain NM522 was transformed with pTrcPgLFMO1 and the PgLFMO was expressed under the control of the Trc promoter. Recombinant PgLFMO isolated from the bacterial lysates was purified to homogeneity and found to have N- and S-oxygenation kinetic properties similar to those of the native enzyme. Stereoselective S-oxygenation of (+)- and (-)-4-bromophenyl-1,3-oxathiolane or 2-methyl-1,3-benzodithiole by the expressed PgLFMO showed some differences from that of the native enzyme, however. These data indicate that active PgLFMO was expressed in E. coli but that the enzyme action was distinct from the native enzyme.

Animals↗
PubMed1993

Pancreatic xanthomatous neuropathy associated with hyperlipidemia: a cause of abdominal pain mimicking chronic pancreatitis.

"Hyperlipidemic crisis" is a term used to describe episodic abdominal pain in patients with hyperlipidemia. The morphologic correlates of this phenomenon have not been investigated and the etiology of the disorder is uncertain. We report a unique histologic finding in the pancreas of a 34-year-old woman with a 17-year history of episodic abdominal pain, sometimes accompanied by hyperamylasemia. At the age of 18 years, grossly elevated cholesterol and triglyceride levels were documented and type V hyperlipidemia was diagnosed. At the age of 34 years, subtotal pancreatectomy was performed for intractable abdominal pain. Histologic examination identified an increased number of enlarged pancreatic nerves that were infiltrated by foamy macrophages and encircled by fibrous tissue; endoneurial infiltration with macrophages occasionally split nerves into individual fascicles. Otherwise, the pancreas had only minimal fibrosis, nesidioblastosis, mucinous metaplasia of some pancreatic ducts, and scattered small collections of chronic inflammatory cells, subtle features suggesting very mild chronic pancreatitis. We propose that this novel xanthomatous neuropathy mimicked pancreatitis and was one of the underlying pathophysiologic mechanisms of abdominal pain in this patient. Further studies are necessary to document the prevalence of this new entity in patients with hyperlipidemia and to correlate its occurrence with "hyperlipidemic crisis" in those individuals.

Abdominal Pain↗
PubMed1993

Picrotoxin-induced seizures modified by morphine and opiate antagonists.

The effects of naloxone, Tyr-MIF-1, and MIF-1 on morphine-mediated changes in susceptibility to picrotoxin-induced seizures were studied. Rats were pretreated with naloxone, MIF-1, Tyr-MIF-1, or saline. At 15-min intervals, they received a second pretreatment of morphine or saline and then were tested for seizures following a convulsant dose of picrotoxin. Several parameters of specific categories of seizures were scored. Morphine increased the number of focal seizure episodes, duration of postseizure akinesis, and incidence of generalized clonic seizures. Naloxone tended to block the morphine-mediated changes in susceptibility. Tyr-MIF-1 had effects similar to naloxone on duration of postseizure immobility but tended to potentiate the effects of morphine on focal seizure episodes. The effects of morphine and the opiate antagonists on focal seizure episodes and postseizure duration suggest the general involvement of several types of opiate receptors in these picrotoxin-induced behaviors. However, the observation of antagonistic effects for Tyr-MIF-1 on immobility but agonistic effects for focal seizures suggests that the type of effect exerted by opiate agents may depend upon other neuronal variables.

Animals↗
PubMed1993

Picrotoxin-induced behavioral tolerance and altered susceptibility to seizures: effects of naloxone.

The role of opiate mechanisms in the development of tolerance and altered susceptibility to seizures after repeated injections of picrotoxin was investigated. Independent groups of rats were pretreated with naloxone (0.3, 1.0, 3.0, and 10.0 mg/kg) or the saline vehicle and then tested for seizures induced by picrotoxin. The procedure was performed on 3 days at 1-week intervals, for a total of 3 testing days. Latencies to different types of seizures, the duration of postseizure immobility, and the number of focal seizure episodes were scored. In the vehicle-treated group, repeated picrotoxin injections led to an increased susceptibility to myoclonic and focal seizures and to decreased duration of postseizure immobility. Naloxone pretreatment significantly decreased the duration of the postseizure akinetic periods in the 1.0- and 10.0-mg/kg groups across all days, suggesting that endogenous opiates are involved in postseizure immobility and that there are interactions between opiate and picrotoxin mechanisms in some seizure-related behaviors. Naloxone did not alter the development of tolerance or sensitivity, indicating that naloxone-insensitive opiate mechanisms or nonopiate mechanisms may be involved in these processes.

Animals↗
PubMed1993

Prevalence of coronary heart disease in the rural population of Thiruvananthapuram district, Kerala, India.

To establish the prevalence, with 95% confidence limits, of some of the indicators of coronary heart disease in the rural population of Thiruvananthapuram district, Kerala state, India, we did a field survey on a cluster sample with probability proportionate to size (PPS sample) of 500 households from five villages. Altogether the sample consisted of 1253 individuals who were more than 25 years of age, of which 1130 responded (90%). The survey instruments included the Malayalam translation of the Rose questionnaire, a standard 12-lead electrocardiogram with a battery operated portable electrocardiograph machine, blood pressure measurements using a mercury sphygmomanometer, and routine anthropometric measurements. The prevalence rates estimated were: (a) ECG changes suggestive of coronary heart disease, 36/1000 (95% C.L., 18, 55), (b) Rose questionnaire angina, 48/1000 (95% C.L. 35, 62), (c) definitive evidence of coronary heart disease, 14/1000 (95% C.L., 7, 21), (d) possible evidence of coronary heart disease, 74/1000 (95% C.L., 55, 93). Prevalence of major risk factors were, (a) hypertension by the WHO criteria, 179/1000 (95% C.L., 137, 221), (b) smoking, 219/1000 (95% C.L., 151, 287), (c) diabetes, 40/1000 (95% C.L., 17, 63), (d) obesity, 55/1000 (95% C.L., 6, 104). We have found that objective criteria indicate a lower prevalence of coronary heart disease in rural Thiruvananthapuram district when compared to studies from urban centres in India, but the prevalence of angina by Rose questionnaire is greater.

Adult↗
PubMed1993

Long-term caloric restriction improves baroreflex sensitivity in aging Fischer 344 rats.

The effects of aging and caloric restriction on mean arterial pressure (MAP), heart rate (HR), and baroreflex sensitivity were determined in young (7-9 months) and old (22-24 months) awake, male Fischer 344 rats which had been either ad libitum fed or calorie restricted (60% of the ad libitum calories). The MAP of young rats was higher than that of old rats. The MAP of old ad libitum fed rats was higher than that of old restricted rats with no effect of diet in young rats. The HR of restricted rats was lower than ad libitum fed rats with no significant age effect. Reflex bradycardia to hypertensive episodes was greater in restricted than in ad libitum fed rats. Reflex tachycardia to hypotensive episodes was greater in young than in old rats and greater in calorie restricted than in ad libitum fed rats. These findings demonstrate that caloric restriction alters the age-associated decline in several hemodynamic parameters.

Aging↗
PubMed1993

Novel approach to the interpretation of long-term "deterioration" in ejection fraction in individual patients with coronary artery disease.

OBJECTIVE: The long-term predictability of left ventricular ejection fraction (LVEF) measurements was evaluated with particular emphasis on the assessment of deterioration in individual patients whose coronary artery disease was initially treated medically. DESIGN: Prospective pilot study. SETTING: Regional cardiac centre. PATIENTS: 60 minimally symptomatic patients with coronary artery disease who, after arteriography, were initially treated medically. INTERVENTION: Measurement of LVEF by first pass exercise radionuclide ventriculography at baseline and six months later without interruption of usual anti-ischaemic medication. Baseline and six-month studies were analysed independently of each other. MAIN OUTCOME MEASURE: Based on 51 patients who remained event free, 95% prediction intervals were derived for prognostic LVEF indices to suggest the minimum change from baseline that might be considered clinically important in the individual patient, alerting clinicians to the need for closer review. RESULTS: At six-month ventriculography, 22 patients showed apparent deterioration in exercise LVEF or the change in LVEF with exercise (delta LVEF). Only two patients had six-month values below the lower limit of 95% prediction intervals, compared with 15 when 95% group confidence intervals (z = 3.33, p < 0.001) were used. When delta LVEF = 0 at baseline, the lower limit of 95% prediction intervals allowed for an exercise induced fall at six months of < or = 13%. For a baseline exercise LVEF of 50% (just normal), the lower limit of 95% prediction intervals was 38%--that is, the exercise LVEF could be measured as low as 38% > or = six months later without necessarily indicating or missing true deterioration. CONCLUSION: In the follow up of minimally symptomatic patients with coronary artery disease, serial long-term changes, in particular "deterioration," in prognostic LVEF indices may be interpreted more meaningfully with reference to 95% prediction intervals.

Adult↗
PubMed1993

Plasma and 24 h-urinary catecholamine concentrations in normal and patient populations.

Using a single HPLC-ECD methodology, plasma catecholamine data were compiled from 545 patients and 144 healthy subjects, and 24 h urinary free catecholamine data from 106 patients. From these data, normal reference ranges were derived for the clinical investigation of suspected phaeochromocytomas, specifically to address the question as to when a result is normal and when further investigation may be required. We have shown that noradrenaline and adrenaline concentrations in plasma and urine are not normally distributed, and basal plasma noradrenaline is significantly lower in normal volunteers than in hospital patients. We have also demonstrated that a reference range which does not take account of these factors will give a significant number of false-positive results. Age and sex did not appear to be significant variables for either plasma or urinary catecholamines. In the investigation of phaeochromocytoma, 95% confidence limits may be used as a warning to repeat sampling and 99% confidence limits as rendering the diagnosis extremely probable. In patients with phaeochromocytomas, urinary catecholamines had a 99.5% specificity and 100% sensitivity in the diagnosis, and thus provide for a rapid and efficient diagnostic screen.

Adolescent↗
PubMed1993

Clinical staging versus laparotomy and combined modality with MOPP versus ABVD in early-stage Hodgkin's disease: the H6 twin randomized trials from the European Organization for Research and Treatment of Cancer Lymphoma Cooperative Group.

PURPOSE: To compare (1) clinical staging and irradiation alone versus staging laparotomy and treatment adaptation in patients with a favorable prognosis (H6F); (2) two combined modalities in patients with an unfavorable prognosis (H6U). PATIENTS AND METHODS: The H6F trial (n = 262) consisted of randomization to clinical staging plus subtotal nodal irradiation (STNI) or to staging laparotomy plus treatment adaptation (adjuvant chemotherapy [CT] only in the 33% with negative laparotomy). The H6U trial (n = 316) consisted of no laparotomy, randomization to mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) or doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD), and mantle irradiation. RESULTS: In the H6F trial, 6-year freedom from progression (FFP) rates (78% v 83%; P = .27) were similar in clinical and laparotomy stagings, respectively. Survival rates were 93% and 89%, due to laparotomy-related deaths. In the H6U trial, the ABVD arm had superior results (6-year FFP rate, 88% v 76%; P = .01), but they were not significant for survival (91% v 85%; P = .22). CT discontinuation due to hematologic intolerance occurred more often with MOPP (14.5% v 7.3%). Decrease of the pulmonary vital capacity ([VC] < 70% of the theoretic value) was observed more frequently after ABVD than after MOPP (12% v 2%; P = .08), with two lethal pulmonary insufficiencies occurring in the ABVD arm. No modification of the isotopic left ventricular ejection fraction (LVEF) occurred. Gonadal toxicity was less in the ABVD arm. CONCLUSION: Early-stage patients benefit from treatment adaptation to initial characteristics in terms of tumor control and late toxicities. Staging laparotomy before STNI may be deleted even in favorable patients at no cost to survival or FFP. In unfavorable patients, ABVD achieved better results than MOPP, at lower hematologic and gonadal cost. Therefore, despite its pulmonary toxicity, ABVD is the best choice to design improved CT regimens associated with mantle irradiation.

Adolescent↗
PubMed1993

Late relapse in early-stage Hodgkin's disease patients enrolled on European Organization for Research and Treatment of Cancer protocols.

PURPOSE: The great majority of relapses after the treatment for early-stage Hodgkin's disease are observed within 4 to 5 years after treatment completion. This study describes the characteristics and outcome of patients who had late relapses, which was defined as relapses that occurred 5 or more years after initial treatment start. PATIENTS AND METHODS: A total of 1,082 adult patients with early clinical stage Hodgkin's disease were enrolled on three consecutive European Organization for Research and Treatment of Cancer (EORTC) protocols (H1, H2, and H5 trials) from 1964 to 1981. Of these, 1,044 patients satisfied the eligibility criteria with a supradiaphragmatic localization, age greater than 15 years, and initial complete remission. Overall, 341 patients (32.6%) relapsed, 304 (29.1%) early and 37 (3.5%) late. For each of these 37 late relapsers, questionnaires were sent to the participating centers and detailed information for 34 relapses was obtained. Cumulative probabilities for developing a late relapse were estimated using the Kaplan and Meier method. Quantification of the relationship between late relapse and several confounding variables was performed using the Cox's proportional hazards model. RESULTS: The 10- and 15-year cumulative probabilities of late relapse in patients who were disease-free at 5 years were 4.8% and 8.3%, respectively. Patients treated on more recent protocols had a higher incidence of late relapse, possibly due to an attempt to tailor therapy to the specific prognostic factors (10-year cumulative probabilities, 4.6%, 2.6%, and 7.5% in trials H1, H2, and H5, respectively). Incidence of late relapses significantly correlated with male sex, B symptoms, mediastinal involvement, and treatment modality. Salvage treatment induced a complete response in 27 patients (79%) and a prolonged complete remission in 24 patients (71%). Twenty years after initial treatment start, similar overall survival rates were observed for late relapsing (72%) and nonrelapsing patients (75%). CONCLUSION: Late relapses of Hodgkin's disease are uncommon, but may be more frequent with recent protocols tailored to specific prognostic factors. If treated, their outcome is favorable. Late relapse is therefore another factor indicating that careful, long-term follow-up is needed for patients with Hodgkin's disease.

Adolescent↗
PubMed1993

Two effects of context on the presence/absence of connecting segments.

Stimulus A consisted of two proximal brackets with colinear lines separated by small gaps. Stimulus B was a square-like rectangle produced by inserting connecting segments into the gaps. Stimulus A was frequently represented as B (i.e., as closed). Following Pomerantz and Pristach (1989) and Treisman and Paterson (1984), perhaps A produced a closure emergent feature that was salient but otherwise independent of other features. However, adding the same two vertical lines (context) to both A and B produced a contrasting division outcome, even though the putative closure emergent feature was an element of the A+context stimulus, and even though it matched a physical feature of the B+context stimulus. Therefore, this emergent feature did not produce the closure. Two additional experiments indicated that the two context lines made the two connecting segments more visible--a context-produced increase in visibility occurred that is not comparable to other known evidence of perceptual improvement. This greater visibility also indicates that the division was not due to the two context lines inhibiting the perception of the two connecting segments, and the closure was not due to good continuation.

Contrast Sensitivity↗
PubMed1993

Hyperprolactinemia in women--a series of 71 cases.

Seventy one cases of hyperproloactinemia (HPRL) in women were seen over five years. Of these, twenty five had pituitary tumors, thirty three had functional HPRL, five had drug induced HPRL and four had hypothyroidism. Surgery was undertaken in fifteen women, rest were treated with bromocriptine. There were thirteen pregnancies in patients with tumor after treatment. Seven of thirty three patients with functional HPRL conceived. No patient had tumor expansion or recurrence during pregnancy. Bromocriptine was required for most patients.

Adult↗