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Biomedical subjects

L Brady

Publications and source records attributed to L Brady.

At least 55 records · Page 3Linked to original sources
PubMed1990

Calcium binding in alpha-amylases: an X-ray diffraction study at 2.1-A resolution of two enzymes from Aspergillus.

X-ray diffraction analysis (at 2.1-A resolution) of an acid alpha-amylase from Aspergillus niger allowed a detailed description of the stereochemistry of the calcium-binding sites. The primary site (which is essential in maintaining proper folding around the active site) contains a tightly bound Ca2+ with an unusually high number of eight ligands (O delta 1 and O delta 2 of Asp175, O delta of Asn121, main-chain carbonyl oxygens of Glu162 and Glu210, and three water molecules). A secondary binding site was identified at the bottom of the substrate binding cleft; it involves the residues presumed to play a catalytic role (Asp206 and Glu230). This explains the inhibitory effect of calcium observed at higher concentrations. Neutral Aspergillus oryzae (TAKA) alpha-amylase was also refined in a new crystal at 2.1-A resolution. The structure of this homologous (over 80%) enzyme and additional kinetic studies support all the structural conclusions regarding both calcium-binding sites.

Amino Acid Sequence↗
PubMed1990

A serine protease triad forms the catalytic centre of a triacylglycerol lipase.

True lipases attach triacylglycerols and act at an oil-water interface; they constitute a ubiquitous group of enzymes catalysing a wide variety of reactions, many with industrial potential. But so far the three-dimensional structure has not been reported for any lipase. Here we report the X-ray structure of the Mucor miehei triglyceride lipase and describe the atomic model obtained at 3.1 A resolution and refined to 1.9 A resolution. It reveals a Ser..His..Asp trypsin-like catalytic triad with an active serine buried under a short helical fragment of a long surface loop.

Amino Acid Sequence↗
PubMed1990

The radiation therapy of early stage cutaneous T-cell lymphoma.

Results of different radiotherapy schedules used for early stage (T1-2, N0-1, M0) cutaneous T-cell lymphoma (CTCL) are compared in a series of 45 patients (22 patients treated with high dose total skin electron beam therapy (TSEB) with curative intent, 18 patients treated with palliative radiotherapy, and 5 patients treated with high dose local electron beam). At 3, 5, and 10 years after diagnosis the high dose TSEB treatment group had a probability of overall survival of 91%, 86%, and 75%, respectively, compared with 94%, 88%, and 88% for the palliative treatment group. The complete response (CR) rate for the high dose TSEB treatment group was 82% (18/22), compared with a 57% (4/7) complete response rate for seven patients in the palliative group who received low dose TSEB (less than 25 Gy in 6-7 weeks) followed by daily application of topical mechlorethamine hydrochloride (HN2). However, the probability of continued remission at 3, 5, and 10 years was 44%, 44%, and 33%, respectively, for the high dose TSEB group and 25%, 25%, and 0%, respectively, for the low dose TSEB + HN2 group. The median disease-free survival was 17.5 months for the high dose TSEB group versus 5.5 months for the low dose TSEB + HN2 group. The five patients who were treated with high doses of local electrons to a single local field had an overall survival rate of 80%, a median survival rate of 64 months, and a median length of continued remission of 31 months. These results indicate that high-dose electron beam can result in long-term disease-free survival in patients with localized and limited extent skin involvement with cutaneous T-cell lymphoma.

Adult↗
PubMed1988

Motor and sensory abilities with normal and academically at-risk children.

Motor and sensory abilities were assessed with children identified as normal and children identified as academically at-risk. The children were grouped based on the results of a screening procedure which consisted of tasks designed to assess academic readiness skills. The results indicated that the academically at-risk children did significantly poorer on most of the measures of motor and sensory functioning. Discriminant analyses indicated that the measures were generally more effective at classifying the normal children than the academically at-risk children. The results are discussed in relation to developmental models of neuropsychological functioning.

Journal Article↗
PubMed1987

Campylobacter pyloridis gastritis II: Distribution of bacteria and associated inflammation in the gastroduodenal environment.

The distribution of Campylobacter pyloridis in the stomach and duodenal bulb of two series of patients (n = 53) with dyspeptic symptoms was studied. In all patients where a comprehensive search of the stomach was conducted, C. pyloridis and active chronic gastritis were associated. That is, the presence of this organism anywhere in the stomach may be taken as a marker of active chronic gastritis within that stomach, although not necessarily at the site of bacterial detection. Two main patterns of colonization are proposed: C. pyloridis either colonizes normal antra and extends proximally along the lesser curvature and into the body with subsequent development of active chronic gastritis and/or the bacterium colonizes areas of chronic-only gastritis induced by other agents resulting in active chronic gastritis. As C. pyloridis may be limited to the antrum or body of any given stomach, it is necessary to biopsy both areas when looking for the bacterium.

Campylobacter↗
PubMed1986

Campylobacter pyloridis and gastritis: association with intercellular spaces and adaptation to an environment of mucus as important factors in colonization of the gastric epithelium.

Stomach biopsy specimens from greater than 40 individuals with Campylobacter pyloridis-associated gastritis were examined by light and electron microscopy. The bacteria were consistently seen in two locations: within the gastric mucus and associated with intercellular junctions of gastric epithelial cells. C. pyloridis is suggested to be one of a broad group of spiral bacteria that are adapted to the peculiar niche provided by intestinal mucus. The spiral morphology and the form of motility of these organisms give them a selective advantage in a viscous environment. This point has been demonstrated in vitro by measurement of the velocity of clinical isolates in solutions of methyl cellulose of varying viscosity. The localization of C. pyloridis close to intercellular junctions is proposed to be due to the presence of preferred metabolites or growth factors, e.g., urea and hemin. All isolates show an extremely high urease activity and require hemin for growth.

Campylobacter↗
PubMed1985

Psychological, nutritional and physical status of olympic road cyclists.

Six members of the Irish Olympic Road Cycling Squad underwent a comprehensive medical, nutritional, psychological and biochemical assessment in January 1983. They were given specific medical and dietary recommendations and were reassessed in January 1984 after a period spanning the competitive racing season. The cyclists' diets at both sessions were comparable and generally conformed with recommended daily intakes. Supplementary ingestion was unnecessary to attain recommended daily intakes of vitamins. Serum levels of HDL-cholesterol increased and triglyceride decreased during the period of the study. The squad had characteristics indicating traits of self-sufficiency, toughness and practical mindedness. At the second assessment there was evidence of heightened ambition and competitiveness and an improvement in mood states with reduced ratings for confusion and tension.

Adult↗
PubMed1982

Antibiotic-resistant staphylococci in a teaching hospital.

A large, continuing outbreak of infection and colonisation with a Staphylococcus aureus which is resistant to methicillin and gentamicin is reported. Affected patients and staff members seen between September, 1980, and August, 1981, are reviewed in detail. Methods of management of such persons and their treatment, if required, are discussed. The antibiotic-resistant Staph. aureus is readily disseminated in hospitals and may cause outbreaks of infection in wards, which require isolation of affected patients in the attempt to control the problem. It is suggested that a special isolation unit is needed. Use of the few effective antibiotic agents should be restricted. Despite these measures, the spread of this organism may not be contained.

Adult↗
PubMed1980

Irradiation as the primary management of stage I and II adenocarcinoma of the breast: analysis of the RTOG breast registry.

The radiation therapy oncology group, a 36-member national study group, has collected, by means of a registry, 234 patients treated with primary irradiation for UICC Stage I and II adenocarcinoma of the breast. Analysis of these patients has revealed a 5-year actuarial survival rate of 83% for Stage I and 68% for Stage II. The local-regional failure rate for all 234 patients was 8.5% (20/234), and 16.6% (17/102) for those patients followed for a minimum of 3 years. The local failure rate for T1 tumors was negligible, being 1.7% (2/117), regardless of whether or not complete excision of tumor was performed prior to irradiation. For T2 tumors, the local failure rate was 9.7% (9/93) if there was preirradiation tumor excision, but increased to 29.2% (7/24) if the preirradiation surgery was limited to incisional or needle biopsy only. There were six severe complications (2.6%), and all of these were cases of breast fibrosis. There were 14 other complications but these were judged to be of only mild to moderate severity. Eighty-four percent of the patients had an acceptable cosmetic result with either no difference or only a mild to moderate difference between the treated and untreated breast.

Adenocarcinoma↗
PubMed1976

Staging laparotomy for Hodgkin's disease.

We reviewed 39 patients with untreated Hodgkin's disease who underwent staging laparotomy and such cases in the English literature over the past two-and-a-half years. In the group of institutions in our compilation, the accuracies of clinically positive and negative judgments of liver involvement were 28 per cent and 95.4 per cent respectively, while in our institution the accuracies were 100 per cent and 95 percent respectively. The accuracies of the clinically positive and negative determinations of splenic involvement were 61.2 per cent and 67.3 per cent respectively after histological examination, whereas we had accuracies of 100 per cent and 74 per cent respectively. The accuracies of the clinically positive and negative determination of lymph nodes were 72.1 per cent and 86.7 per cent respectively, whereas the results were 70.6 per cent and 100 per cent respectively in our 39 cases. The percentage of complications was 10 per cent and the mortality rate was 0.9 per cent among 719 staging laparotomies. The common complications were atelectasis, pneumonia, wound infection and dehiscence, abscess, intestinal obstruction and thrombocytosis. We think more aggressive staging laparotomy should be performed for Hodgkin's disease under one surgeon or one surgical team.

Adolescent↗
PubMedDate not supplied

Effects of serotonergic agonists and antagonists on corticotropin-releasing hormone secretion by explanted rat hypothalami.

Experimental evidence suggests that serotonin (5HT) is excitatory to the hypothalamic-pituitary-adrenal axis and that this effect involves activation of both hypothalamic corticotropin-releasing hormone (CRH) and pituitary ACTH secretion. The present study was undertaken to examine the mechanism by which 5HT stimulates the central component of the HPA axis. To accomplish this we employed an in vitro rat hypothalamic organ culture system in which CRH secretion from single explanted hypothalami was measured by specific radioimmunoassay (IR-rCRH). All experiments were performed after an overnight (15-18 hr) preincubation. Serotonin stimulated IR-rCRH secretion in a dose-dependent fashion. The response was bell-shaped and the peak effect was observed at the concentration of 10(-9) M. The stimulatory effect of 10(-9) M 5HT was antagonized by the 5HT1 and 5HT2 receptor metergoline and by the selective 5HT2 receptor antagonists ketanserin and ritanserin. The muscarinic antagonist atropine, the nicotinic antagonist hexamethonium and the alpha-adrenergic receptor antagonist phentolamine, on the other hand, did not inhibit 5HT-induced IR-rCRH secretion. The specific 5HT2 receptor agonist 1-(2,5-dimethoxy-4-iodo-phenyl)-2-aminopropane (DOI) stimulated IR-rCRH secretion in a dose-dependent fashion. The response was bell-shaped with peak of effect reached at the concentration of 10(-9) M. We also tested the ability of the 5HT agonist meta-chlorophenylpiperazine (m-CPP) and of the selective 5HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) to cause CRH secretion. Although both m-CPP and 8-OH-DPAT stimulated IR-rCRH secretion in a dose-dependent fashion, several differences were observed when their effect was compared to that of 5HT. These included a different shape of the dose-response curve, a lower maximal stimulatory effect and a different maximal stimulatory concentration. These findings suggest that serotonin stimulates CRH secretion by explanted rat hypothalami and that this effect appears to be mediated mainly through a 5HT2 receptor mechanism.

Animals↗