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Biomedical subjects

T Atkinson

Publications and source records attributed to T Atkinson.

At least 19 recordsLinked to original sources
PubMed2006

Phase I/II dose finding study of combination cisplatin and gemcitabine in patients with recurrent cervix cancer.

OBJECTIVES: To evaluate the toxicity and efficacy of cisplatin and gemcitabine in women with recurrent cervical cancer. METHODS: A multi-institutional phase I/II dose finding study of cisplatin and gemcitabine delivered to women with recurrent previously radiated cervical carcinoma. RESULTS: Twenty eight patients were enrolled. The mean and median age of patients was 51 years (age range 35 to 70 years). Chemotherapy was given on a 28-day cycle; cisplatin was administered at a fixed dose of 50 mg/m(2), day 1 and gemcitabine, days 1, 8, and 15. Gemcitabine doses started at 600 mg/m(2) (dose level 1) and were escalated by 100 mg/m(2)/dose level until 1000 mg/m(2) (dose level 5). Twenty seven patients were evaluable for toxicity and disease response, and 75 cycles of chemotherapy were administered. Toxicities were predominantly hematological; 18% of patients experienced grade 3 anemia, 37% grade 3 and 11% grade 4 leukopenia, 41% grade 3 neutropenia, and 26% grade 3 thrombocytopenia. The maximally tolerated dose (MTD) was not reached. One patient experienced a dose-limiting toxicity on dose level 2 (febrile neutropenia). One patient had a CR and 3 patients had a PR to therapy (15% response rate), 41% of patients had SD, and 44% had progression of cancer. Median survival was 11.9 months. CONCLUSION: Although this 28-day gemcitabine and cisplatin regimen in recurrent cervix cancer has tolerable toxicity, 21-day regimens are recommended because of improved practicality, higher dose intensity, and higher response rates.

Adult↗
PubMed2001

Resisting and promoting new technologies in clinical practice: the case of telepsychiatry.

New telecommunications technologies promise to profoundly change the spatial and temporal relationship between health professional and patient. This paper reports results from an ethnographic study of the introduction of a videophone or 'telemedicine' system intended to facilitate faster and more convenient referral of patients with anxiety and depression in primary care, to a community mental health team. We explore the reasons for contest over the telemedicine system in practice, contrasting professionals' critique of the technology in play with a more fundamental problem: the extent to which the telecommunications system threatened deeply embedded professional constructs about the nature and practice of therapeutic relationships.

Anxiety Disorders↗
PubMed2000

Transient NMDA receptor inactivation provides long-term protection to cultured cortical neurons from a variety of death signals.

NMDA receptor antagonists, such as (+)-5-methyl-10, 11-dihydro-5H-dibenzo [a,d] cyclohepten-5,10-imine maleate (MK-801), potently block glutamate-induced neuronal death in myriad in vitro cell models and effectively attenuate ischemic damage in vivo. In this report, a novel role for MK-801 and other NMDA receptor antagonists in preconditioning neurons to withstand a wide range of subsequent lethal insults is described. A brief 30 min exposure to 0.1 microM MK-801, applied up to 96 hr before a "lethal" insult, protected primary cortical neurons from a diverse group of neurotoxic agents, including NMDA, beta-amyloid, staurosporine, etoposide, and oxygen-glucose deprivation. This neuroprotective preconditioning by MK-801 arose from transient NMDA receptor inactivation, because the noncompetitive NMDA receptor antagonists memantine and nylindin and the competitive antagonist AP-5 gave similar effects. MK-801 protection was dependent on new protein synthesis during the first 2 hr, but not from 2 to 5 hr, after MK-801 exposure. The MK-801 transient did not alter the ability of NMDA to trigger normally lethal [Ca(2+)](i) influx 48 hr later, but it did block early downstream signaling events coupled to NMDA neurotoxicity, including PKC inactivation and the activation of calpain. Moreover, MK-801 protected neurons from staurosporine-induced apoptosis, although caspase activation in these cells was unimpeded. It is likely that the stress associated with transient inactivation of NMDA receptors triggered a rapid compensatory survival response that provided long-term protection from a spectrum of insults, inducing apoptotic and nonapoptotic death. The possibility that MK-801 preconditioning blocks an event common to seemingly diverse death mechanisms suggests it will be an important tool for obtaining a clearer understanding of the salient molecular events at work in neuronal death and survival pathways.

Adrenergic beta-Agonists↗
PubMed2000

A microbiological survey of Montserrat Island hydrothermal biotopes.

In March 1996, a survey of hydrothermal sites on the island of Montserrat was carried out. Six sites (Galway's Soufrière. Gages Upper and Lower Soufrières, Hot Water Pond, Hot River, and Tar River Soufrière) were mapped and sampled for chemical, ATP, and microbial analyses. The hydrothermal Soufrière sites on the slopes of the active Chances Peak volcano exhibited temperatures up to almost 100 degrees C and were generally either mildly acidic at pH 5-7 or strongly acidic at pH 1.5-3, but with some hot streams and pools of low redox potential at pH 7-8. Hot Water Pond sites, comprising a series of heated pools near the western shoreline of the island. were neutral and saline, consistent with subsurface heating of entrained seawater. Biological activity shown by ATP analyses was greatest in near-neutral pH samples and generally decreased as acidity increased. A variety of heterotrophic and chemolithotrophic thermophilic organisms were isolated or observed in enrichment cultures. Most of the bacteria that were obtained in pure culture were familiar acidophiles and neutrophiles, but novel, iron-oxidizing species of Sulfobacillus were revealed. These species included the first mesophilic iron-oxidizing Sulfobacillus strains to be isolated and a strain with a higher maximum growth temperature (65 degrees C) than the previously described moderately thermophilic Sulfobacillus species.

Adenosine Triphosphate↗
PubMed2000

Knee injuries in motor vehicle collisions: a study of the National Accident Sampling System database for the years 1979-1995.

A detailed study of knee injuries recorded in the 1979-1995 National Accident Sampling System database maintained by the National Highway Traffic Safety Administration was conducted. Injuries to other body regions were also considered in order to illustrate the relative frequency of knee injuries. This study demonstrated that knee injuries constitute approximately 10% of all injuries recorded every year. However, the majority of these injuries were of low severity (i.e. contusions, abrasions, lacerations) with an abbreviated injury score (AIS) of 1. Most knee injuries occurred following a frontal collision with no intrusion. The study also indicated most knee fractures occur in crashes where the vehicle velocity differences (deltaVs) were less than 45 kmph, with some occurring at deltaVs as low as 10 kmph. Serious non-fracture knee injuries (i.e. ligament tears) rated AIS 2 accounted for 20 out of every 1000 injuries and predominantly occurred at deltaVs below 25 kmph. In this study it was noted that women were more likely to experience a knee contusion than men. This study further suggests that knee impact scenarios have remained relatively constant over the years as the knee injury rates showed little variation. The rate of lap and shoulder belt use was lower in occupants who experienced a knee injury vs. the rate in the overall database and airbags were present in only a small number of cases. As this study largely included only vehicles without airbags it provides a good baseline for analysis of the influence of the airbag on knee injury trends in the future.

Accidents, Traffic↗
PubMed2000

Telepsychiatry evaluation in the north-west of England: preliminary results of a qualitative study.

A telepsychiatry referral service for patients suffering from anxiety and depression was evaluated from a user perspective. Low-cost video-phones linked a psychiatrist to two general practices in the north-west of England. Quantitative data were collected using a semistructured interview schedule. Twenty-two patients and 13 doctors were interviewed after a video-link consultation. Some users were very positive about the service and recognized its potential benefits, while others were more ambivalent. Patients saw the service as a means of obtaining additional 'expert' advice. General practitioners felt that the service might adversely affect the doctor-patient relationship in psychiatry. Both patients and clinicians recognized that the video-link modified normal interaction. Users need to adapt to this form of communication. An induction session is recommended for both patients and clinicians.

Anxiety↗
PubMed1999

Secretion of pancreatic digestive enzymes induced in rats by first-time oral exposure to kidney bean E2L2 lectin is mediated only in part by cholecystokinin (CCK).

The acute effects of kidney bean (Phaseolus vulgaris) E2L2 lectins (PHA) given orally to conscious rats or continually infused into the duodenum of anesthetized rats on blood cholecystokinin (CCK), secretin, and gastrin and on secretion of pancreatic digestive enzymes have been evaluated. PHA increased circulating levels of CCK and secretin but did not alter gastrin. In addition, PHA induced dose-dependent secretion of trypsinogen, chymotrypsinogen, and alpha-amylase by the pancreas in vivo. This pancreas output appeared to be modulated only in part through CCK. Thus pretreatment of rats with a CCK-A receptor antagonist (L-364718) attenuated the immediate (< or = 90 min) pancreas secretory response to PHA but could not prevent a PHA-associated increase in digestive enzyme output in the longer term (after 90 min). In contrast, treatment of rats with L-364718 abolished the stimulatory effects of soyabean trypsin inhibitors on digestive enzyme secretion in both the short and long term. Additional mechanisms or hormones, such as secretin, may play a role in modulating later exocrine pancreas responses to PHA.

Animals↗
PubMed1999

Psychiatry by videophone: a trial service in north west England.

In this paper we report on the use of a video link between two general practices and a hospital based mental health team in North West England to provide a trial telepsychiatry service for individuals with depression and anxiety related disorders. Patients (n = 16) took part in an evaluation of the service by both structured questionnaire and semi-structured interview. The results of the evaluation study suggest that patients may be highly critical of telemedicine systems and that they do so not simply on the grounds of the technical quality of video links, but also because the remote link increases the difficulty that the patient faces in expressing deep scated emotional and existential problems. It is not, therefore, simply a matter of technical quality in the link, but also a question of the quality of interpersonal relations perceived by the patient.

Adult↗
PubMed1998

Leptin (ob) mRNA and hypothalamic NPY in food-deprived/refed Syrian hamsters.

Food deprivation in the laboratory rat decreases plasma leptin and insulin, elevates glucocorticoid concentration, and increases the activity of the neuropeptide Y (NPY) system and feeding drive. In contrast, Syrian hamsters fail to modify feeding behaviour in response to various food scarcity paradigms. Two components of the neuroendocrine-hormonal response to food deprivation, adipose tissue-derived leptin and hypothalamic NPY, are investigated in the Syrian hamster. ob (leptin) mRNA was less abundant in subcutaneous than abdominal adipose tissue, but not to the extent observed in other rodents. Food deprivation for 48 h reduced ob mRNA in inguinal and retroperitoneal white adipose tissue; gene expression was partially restored by refeeding. In contrast, in epididymal fat there was no effect on ob mRNA. NPY concentrations in hypothalamic nuclei were also unaffected by feeding state. The predicted amino acid sequence of leptin from the Syrian hamster was over 90% homologous with Djungarian hamster and mouse sequences, and the leptin receptor gene (OB-R), and specifically the long intracellular splice variant, OB-Rb, was expressed in the same forebrain and hypothalamic regions that have been described in laboratory mice and rats, including hypothalamic arcuate, dorsomedial, and ventromedial nuclei. The failure of food deprivation to affect NPY and feeding behaviour in Syrian hamsters is unlikely to be due to defects in the leptin system, although there may be region-specific differences in the regulation of leptin signaling in laboratory rats and Syrian hamsters.

Adipose Tissue↗
PubMed1997

Short-day weight loss and effect of food deprivation on hypothalamic NPY and CRF mRNA in Djungarian hamsters.

The effect of food deprivation on hypothalamic neuropeptide Y (NPY) and corticotropin-releasing factor (CRF) gene expression in the Djungarian hamster was quantified by in situ hybridization. Hamsters housed in short days (SD) for 18 wk decreased body weight by 40% and exhibited 200% increases in both NPY and CRF mRNA when deprived of food for 24 h. Prior gonadectomy in long days (LD) affected neither basal gene expression nor the induction of gene expression by food deprivation. Gene expression in juvenile LD hamsters similar in body weight to SD animals was relatively insensitive to food deprivation of either 24- or 48-h duration or to subsequent refeeding. In juvenile hamsters, food deprivation for 24 but not 48 h decreased ob (obese) gene expression in inguinal but not epididymal white adipose tissue; ob mRNA levels were restored by refeeding. All food-deprived hamsters had reduced plasma insulin concentrations, but plasma cortisol was only elevated in SD food-deprived animals. NPY gene expression was also increased after daily dexamethasone injections in adult LD hamsters. These results suggest that the neuroendocrine consequences of food deprivation in SD Djungarian hamsters are determined by some factor other than absolute body mass such as the size of adipose tissue reserves.

Animal Feed↗
PubMed1996

Regulation of galanin gene expression in the hypothalamic paraventricular nucleus of the obese Zucker rat by manipulation of dietary macronutrients.

Lean and obese male Zucker rats were fed high fat (72% of energy as fat), high carbohydrate (66% of energy as carbohydrate) or intermediate diets for 4 weeks commencing 1 week after weaning. We examined the effects of these diets on growth rates, plasma insulin and corticosterone titres, and hypothalamic gene expression of 3 appetite-related neuropeptides. Messenger RNA levels for neuropeptide Y (NPY), galanin (GAL) and corticotropin-releasing factor (CRF) in critical hypothalamic locations were measured by in situ hybridization in each brain. Obese rats grew more rapidly and had elevated plasma insulin and corticosterone concentrations relative to their lean littermates. The obese phenotype was also associated with elevated NPY gene expression in the arcuate nucleus of the hypothalamus and increased GAL gene expression in the hypothalamic paraventricular nucleus. There was no effect of diet on NPY or CRF gene expression in either lean or obese rats. However, maintenance on the high fat diet had a significant effect on GAL gene expression in obese but not lean rats: high fat diet significantly reduced mRNA levels in the obese rats. This reduction in GAL mRNA was accompanied by attenuation of the hyperinsulinemia that is characteristic of this genetic obesity.

Animals↗
PubMed1996

Hypothalamic NPY and CRF gene expression in the food-deprived Syrian hamster.

Because the Syrian hamster, Mesocricetus auratus, does not increase food intake in response to food deprivation, we investigated whether hypothalamic NPY gene expression in this species was sensitive to this imposed state of negative energy balance. In the rat, food deprivation for 48 h resulted in a 150% increase in total preproNPY gene expression in the arcuate nucleus of the hypothalamus (ARC). NPY gene expression in food-deprived Syrian hamsters did not differ significantly from that of ad lib-fed controls, although there was a trend towards increased mRNA levels in the fasted animals. However, food deprivation for 48 h was associated with a rise in preproCRF mRNA in the paraventricular nucleus of the hypothalamus (PVN) of 80-g, but not 150-g, hamsters. The expected reductions in plasma insulin accompanied food deprivation in the Syrian hamster, but cortisol titre was only elevated in the lower body weight group. NPY gene expression in the Syrian hamster appeared, however, to be sensitive to glucocorticoids; daily administration for 28 days of the synthetic glucocorticoid, dexamethasone, increased ARC NPY mRNA levels by 43%. The response of NPYergic and other hypothalamic neuropeptide systems to food deprivation, and the involvement of neuroendocrine substrates in energy homeostasis, may vary between species.

Animals↗
PubMed1996

Effect of continuous infusion of thyrotrophin-releasing hormone on plasma prolactin and on ovarian activity in melatonin-treated ewes.

Twelve anoestrous ewes maintained under natural photoperiod at 57 degrees N received an oral dose of 3 mg melatonin daily at 15:00 h from 1 May. Starting 41 days later and extending from 11 June until 5 September, six of the ewes were also infused continuously with 0.8 mg thyrotrophin-releasing hormone (TRH) day-1 via subcutaneous osmotic minipumps. The remaining six ewes acted as controls. Behavioural oestrus, ovulation rate and luteal function were determined by exposure to a vasectomized ram, laparoscopy and the measurement of progesterone in peripheral plasma, respectively. TRH infusion stimulated a sustained increase (P < 0.001) in plasma concentrations of thyroxine, tri-iodothyronine and prolactin (thyroxine: 158 +/- 9.3 and 65 +/- 7.7 nmol l-1 for TRH-infused and control ewes, respectively; tri-iodothyronine, 2.6 +/- 0.12 and 1.1 +/- 0.19 nmol l-1 and prolactin, 57 +/- 12 and 11 +/- 2 micrograms l-1). No ewes were in oestrus before TRH infusion and the mean number of behavioural oestrous cycles per ewe during the infusion period was 1.3 +/- 0.33 and 2.5 +/- 0.34 for TRH-infused and control ewes, respectively (P < 0.05). Corresponding mean intervals from 1 May to the onset of the first luteal phase (progesterone > 1 ng ml-1) were 88 +/- 8.9 and 79 +/- 3.5 days (not significant). TRH infusion had no effect on the mean numbers of corpora lutea (1.7 +/- 0.14 and 1.6 +/- 0.20 for TRH-infused and control ewes, respectively), but was associated with a lower mean incidence of normal luteal phases (1.5 +/- 0.43 versus 2.7 +/- 0.21, P = 0.052). Abnormalities in luteal function included delayed initial expression, extended ovarian cycles, suprabasal periovulatory progesterone concentrations and protracted periods of low progesterone secretion between successive ovarian cycles. Thus continuous TRH infusion suppressed plasma prolactin, doubled the circulating concentrations of thyroxine and tri-iodothyronine, and was associated with a wide range of abnormalities in ovarian function and endocrine status, the nature of which varied between ewes.

Animals↗
PubMed1996

Amplified expression and large-scale purification of protein L'.

The gene fragment (PPL') encoding the functional unit of peptostreptococcus protein L was isolated using PCR and expressed in E. coli. As the gene fragment lacked its own promoter, the 5' PCR primer was designed to incorporate an Nde1 restriction site (CATATG) into the gene. This enabled the gene to be cloned in frame into an Nde1 restriction site immediately downstream of a trp promoter. To prevent read through, a stop codon was introduced into the 3' primer. Expression of PPL' was up to 27% total cell protein which compares favourably to the 0.1% total soluble cell protein obtained from the original clone of peptostreptococcus. Following a heat step homogeneous PPL' was recovered by a single anion-exchange chromatography step on Q-Sepharose FF in yields of 90%.

Bacterial Proteins↗
PubMed1995

Crystallization of glycerol dehydrogenase from Bacillus stearothermophilus.

The NAD(+)-linked glycerol dehydrogenase from Bacillus stearothermophilus is a member of the so-called 'iron- containing' class of polyol dehydrogenases. This enzyme has been crystallized in three different forms in the presence of a range of divalent cations and glycerol or NAD+ using the hanging-drop method of vapour diffusion with ammonium sulfate as the precipitant. X-ray photographs have established that the crystals grown in the presence of zinc and glycerol (form A) most likely belong to space group I4(1)22 with cell parameters a = b = 102 and c = 728 A. The crystals grown with zlnc and NAD(+) (form B) belong to the tetragonal system and probably belong to the space group P42(1)2 with cell parameters a = b = 150 and c = 220 A. The crystals grown with lead and glycerol (form C) belong to a primitive orthorhombic system with cell parameters a = 127, b = 178 and c = 173 A. Experiments using the synchrotron radiation source at the DRAL Daresbury laboratory have shown all three crystal types diffract to at least 3 A resolution. Elucidation of the three-dimensional structure of this enzyme will provide a structural framework for this class of polyol dehydrogenases, which are not represented in the database at present, and enable comparisons to be made with enzymes belonging to the other classes.

Journal Article↗
PubMed1995

Catalytic-rate improvement of a thermostable malate dehydrogenase by a subtle alteration in cofactor binding.

The nucleotide-binding fold of many NAD(+)-dependent dehydrogenases contains a conserved acidic amino acid residue which hydrogen-bonds with the 2'- and 3'-hydroxy groups of the adenine-ribose of the cofactor. This residue is highly conserved as aspartate in malate dehydrogenases, except in the thermophilic enzyme from Thermus aquaticus B (TaqMDH), which has glutamic acid-41 in the equivalent position. The catalytic mechanism was dissected to investigate the functional significance of this difference in TaqMDH with respect to a mutant enzyme where glutamic acid-41 was replaced by aspartic acid. The mutant enzyme was found to retain a high degree of protein structural stability to both thermal and chemical denaturation. When compared with the wild-type enzyme the mutant had a higher Km and Kd for both reduced and oxidized cofactors (NADH and NAD+) and a 2-3-fold increase in steady-state kcat in both assay directions. The rate-determining step for the reduction of oxaloacetate by wild-type TaqMDH was shown to be the rate of NAD+ release, which was about 2.5-fold higher for the mutant enzyme. This correlates well with the 1.8-fold higher steady-state kcat of the mutant enzyme and represents an improvement in the steady-state kcat of a thermophilic enzyme at moderate temperature by a conservative amino acid substitution which increases the rate of product release.

Aspartic Acid↗
PubMed1995

Crystallization and X-ray analysis of a single fab binding domain from protein L of Peptostreptococcus magnus.

Protein L is a multidomain cell wall constituent of certain strains of Peptostreptococcus magnus which binds to the variable domain of immunoglobulin kappa-light chains. A single immunoglobulin-binding domain of M(r) = 9000 from this protein has been isolated and crystallized. The crystals are of space group P4(2)2(1)2, with cell dimensions a = b = 66.9 A, c = 68.3 A, and diffract to at least 2.2 A resolution. The asymmetric unit of the crystal contains two molecules of the protein L domain, related by a noncrystallographic 2-fold axis, as revealed by a self-rotation function calculated with native diffraction data.

Bacterial Proteins↗