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Biomedical subjects

M Kelly

Publications and source records attributed to M Kelly.

At least 163 records · Page 9Linked to original sources
PubMed1996

Bone marrow and chelatable iron in patients with protein energy malnutrition.

OBJECTIVES: To examine the iron status of malnourished children by comparing bone marrow iron deposits in children with protein energy malnutrition with those in well-nourished controls, and measuring chelatable urinary iron excretion in children with kwashiorkor. DESIGN: Bone marrow iron was assessed histologically in postmortem specimens from children with kwashiorkor or marasmus, and from controls. Twenty-four-hour urinary iron was measured in children with severe kwashiorkor, half of whom received 10 mg/kg of intramuscular desferrioxamine (DFO) on admission. SETTING: Red Cross War Memorial Children's Hospital, Cape Town. SUBJECTS: Thirteen children with kwashiorkor, 6 with marasmus and 16 well-nourished children underwent bone marrow examination. Urinary iron excretion was assayed in 17 children with kwashiorkor. RESULTS: Stainable iron was present in the bone marrow of half the children with kwashiorkor but in only 1 child in each of the other groups. The median iron excretion was 945.5 micrograms/24 hours in the DFO group compared with 28.5 micrograms/24 hours in the non-DFO group. CONCLUSIONS: There is an apparent excess of iron which may predispose to bacterial infections and free radical-mediated injury in children with kwashiorkor.

Bone Marrow↗
PubMed1995

Crystal structure of the membrane-exposed domain from a respiratory quinol oxidase complex with an engineered dinuclear copper center.

Cytochrome oxidase is a membrane protein complex that catalyzes reduction of molecular oxygen to water and utilizes the free energy of this reaction to generate a transmembrane proton gradient during respiration. The electron entry site in subunit II is a mixed-valence dinuclear copper center in enzymes that oxidize cytochrome c. This center has been lost during the evolution of the quinoloxidizing branch of cytochrome oxidases but can be restored by engineering. Herein we describe the crystal structures of the periplasmic fragment from the wild-type subunit II (CyoA) of Escherichia coli quinol oxidase at 2.5-A resolution and of the mutant with the engineered dinuclear copper center (purple CyoA) at 2.3-A resolution. CyoA is folded as an 11-stranded mostly antiparallel beta-sandwich followed by three alpha-helices. The dinuclear copper center is located at the loops between strands beta 5-beta 6 and beta 9-beta 10. The two coppers are at a 2.5-A distance and symmetrically coordinated to the main ligands that are two bridging cysteines and two terminal histidines. The residues that are distinct in cytochrome c and quinol oxidases are around the dinuclear copper center. Structural comparison suggests a common ancestry for subunit II of cytochrome oxidase and blue copper-binding proteins.

Amino Acid Sequence↗
PubMed1995

Health checks and coronary risk: further evidence from a randomised controlled trial.

OBJECTIVE: To determine the effectiveness of a health check and assess any particular benefits resulting from feedback of plasma cholesterol concentration or coronary risk score, or both. DESIGN: Randomised controlled trial in two Glasgow work sites. SUBJECTS: 1,632 employees (89% male) aged 20 to 65 years. INTERVENTIONS: At the larger work site, (a) health education; (b) health education and feedback on cholesterol concentration; (c) health education and feedback on risk score; (d) health education with feedback on cholesterol concentration and risk score (full health check); (e) no health intervention (internal control). At the other work site there was no health intervention (external control). MAIN OUTCOME MEASURES: Changes in Dundee risk score, plasma cholesterol concentration, diastolic blood pressure, body mass index and self-reported behaviours (smoking, exercise, alcohol intake, and diet) in comparison with internal and external control groups. RESULTS: Comparisons between the full health check and the internal control groups showed a small difference (0.13 mmol/l) in the change in mean cholesterol concentration (95% confidence interval 0.02 to 0.22, P = 0.02) but no significant differences for changes in Dundee risk score (P = 0.21), diastolic blood pressure (P = 0.71), body mass index (P = 0.16), smoking (P = 1.00) or exercise (P = 0.41). Significant differences between the two groups were detected for changes in self-reported consumption of alcohol (41% in group with full health check v 17% in internal control group, P = 0.001) fruit and vegetables (24% v 12%, P < 0.001), and fat (30% v 9%, P < 0.001). Comparison of all groups showed no advantage from feedback of cholesterol concentration or risk score, or both. CONCLUSIONS: The health check only had a small effect on reversible coronary risk. It was effective in influencing self reported alcohol consumption and diet. Feedback on cholesterol concentration and on risk score did not provide additional motivation for a change in behaviour.

Adult↗
PubMed1995

Cloning of the mouse gonadotropin beta-subunit-encoding genes, I. Structure of the follicle-stimulating hormone beta-subunit-encoding gene.

More than 16kb of genomic sequence encompassing the mouse follicle-stimulating hormone beta subunit (FSH beta)-encoding gene was isolated from a 129SvEv mouse genomic library. Comparisons of the nucleotide and deduced amino-acid sequences to the FSH beta sequences of other mammalian species confirm an evolutionarily conserved role of this important protein in reproduction.

Amino Acid Sequence↗
PubMed1995

Comparison of recombinant cyclooxygenase-2 to native isoforms: aspirin labeling of the active site.

The search for isoform-specific enzyme inhibitors has been the focus of much recent research effort. Towards this goal, human recombinant cyclooxygenase-2 (EC 1.14.99.1, prostaglandin H synthase) was expressed in insect cells and purified to > 98% purity. Recombinant enzyme was characterized both by physical methods and activity measurements and shown to be fully active with kinetic properties similar to native COX-2 and COX-1. After detergent extraction, the enzyme had hydrodynamic properties indistinguishable from native bovine COX-1 and corresponded to the enzyme dimer as measured with size-exclusion chromatography. Peptide mapping via Lys-C protease identified a site of N-linked glycosylation and the aspirin covalent modification site. In the presence of heme, aspirin-specifically acetylated Ser-516. The enzyme will be suitable for biophysical studies and may lead to isoform-specific enzyme inhibitors.

Amino Acid Sequence↗
PubMed1995

Dental training.

Explore the source record for details and available documents.

Education, Dental, Continuing↗
PubMed1995

NMDA receptors are involved at the ventrolateral nucleus tractus solitarii for termination of inspiration.

The purpose of the present study was to determine whether blockade of excitatory amino acid receptors at the ventrolateral nucleus of the tractus solitarius would influence respiratory activity. This was done by microinjecting excitatory amino acid receptor antagonists into the ventrolateral nucleus of the tractus solitarius of alpha-chloralose-anesthetized animals while monitoring respiratory activity using a Fleisch pneumotachograph and arterial blood pressure and heart rate. Bilateral microinjection of the NMDA receptor antagonist, 3-[(R)-carboxypiperazin-4-yl]-propyl-1- phosphomic acid (CPP), 5.62 nmol per side, produced an increase in inspiratory duration (+4 +/- 1.6 s, n = 8) which progressed to an apneustic pattern of breathing. Similar results were obtained with CPP microinjected into the ventrolateral nucleus of the tractus solitarius of three vagotomized animals. Bilateral microinjection of a second NMDA receptor antagonist, 2-amino-7-phosphono-heptanoic acid (AP7), 562 nmol per side, produced qualitatively similar effects on respiration as seen with CPP. In contrast, blockade of non-NMDA receptors with 6-cyano-7-nitroquinoxaline-2,3-dione (CNXQ), 0.125 nmol per side, had very little effect on respiration. Activation of NMDA receptors at the ventrolateral nucleus of the tractus solitarius with bilateral microinjection of NMDA, 39 pmol, produced a large increase in expiratory duration (+11 +/- 3 s, n = 8), and apnea during the expiratory phase of the respiratory cycle in half of the animals studied. Similar results were obtained with D,L-alpha-amino-3-hydroxy-5-methyl-4-isoxazol-proprionate (AMPA). These results indicate that an endogenous excitatory amino acid released at the ventrolateral nucleus of the tractus solitarius and acting at the NMDA receptor, plays a significant role in respiratory timing.

2-Amino-5-phosphonovalerate↗
PubMed1995

Intra-observer and inter-observer variability in scoring laparoscopic diagnosis of pelvic adhesions.

The objective of this study was to investigate intra-observer as well as inter-observer variability in the assessment of laparoscopic scoring of adhesive disease. Patients with suspected pelvic adhesions underwent a laparoscopic examination and surgical correction, using a standardized adhesion scoring system for severity as well as for extent of the adhesive process. An active agent or placebo was placed in the peritoneal cavity to discourage reformation of adhesions on a double-blind basis. A second laparoscopy was performed in 6-10 weeks and patients were re-scored. The videotapes were viewed and re-scored by the operator and four other gynaecological surgeons on two occasions, 3 months apart. Both adhesion severity and extent scores were lower following laparoscopic intervention. Reliability coefficients as defined by intra-class correlations were large indicating good reliability (0.778 and 0.758 for severity and extent respectively). Intra-observer (replication) variability was 12% of the total versus 19% for inter-observer variability of adhesion severity. These values were 15.4 and 22.3% of the total respectively, for adhesion extent. Individual observers tended to up-grade severity and minimize extent of adhesions when comparing the second with the first videotape views. The surgeon recorded greater adhesion score differences between the two procedures than the other observers. Though two physicians consistently had higher scores than two others, the intra-observer and interobserver variabilities were acceptable. Consultant review of high quality videotaped laparoscopic procedures is a valid method of independent assessment of operative findings.

Adnexal Diseases↗
PubMed1995

Retained sacral function in children with high level myelodysplasia.

To assess the preservation of sacral function despite denervation higher on the spinal cord in children with myelodysplasia, we examined 151 myelomeningocele patients presenting for urodynamic evaluation from 1980 to 1992 with a lesion at L3 or above on neurological examination. Of the 151 patients 70 (46%) had denervation of the external sphincter on initial evaluation and 81 (54%) had sacral sparing, that is normal or near normal electrical potentials of the external urethral sphincter and/or retained reflexic bladder activity regardless of the presence or absence of sacral reflexes. Of the 81 patients with sacral sparing 57 (70%) had detrusor-sphincter dyssynergia and 21 had synergy or denervation of the sphincter in association with retained detrusor reflexia. Whereas only 18% of children age 1 year or younger with retained sacral function had upper urinary tract deterioration on initial radiological studies (manifested by reflux or hydronephrosis), 57% had deterioration when evaluated after age 1 year. None of the patients without retained sacral function had evidence of upper urinary tract damage at younger than 1 year but 28% of those studied beyond age 1 year had changes. Patients with flaccid lower extremities can retain sacral function, which puts the upper urinary tract at risk of deterioration. Our results show that this risk increases with time.

Adolescent↗
PubMed1995

How have Zambian businesses reacted to the HIV epidemic?

OBJECTIVES: To evaluate the impact of HIV on businesses in Zambia and to assess attitudes towards HIV and HIV education in the workplace. METHODS: The personnel managers of 33 companies with a total workforce of 10,204 in Lusaka and in towns in the Copperbelt were visited by two members of the study team. The study was discussed and a questionnaire about the impact of HIV on their company was explained and left for completion from company records. RESULTS: All 33 questionnaires were returned. HIV was recognised to be a problem by 30 companies questioned. Seven said that it had affected recruitment and 11 production. 23 companies carried out pre-employment medicals. 17 companies demanded that some or all of their employees had an HIV test before employment. Nine companies were sure that a positive HIV test would prevent employment, 15 were unsure saying that there was no particular company policy. Two companies had recently changed their policy and had stopped discriminating against those with HIV. 12 companies had some HIV educational material available for their employees and five had someone (or an organisation that they used) to whom they could refer employees for HIV information and advice. Condoms were provided free to staff by five of the companies. All thought that HIV education in the workplace was an appropriate intervention. Mortality data showed a sevenfold increase in the crude mortality from 0.25-1.8 per 100 person-years from 1987-93, and an increasing trend in reported deaths from AIDS and HIV related conditions. CONCLUSIONS: HIV is having an important impact in the workplace in urban Zambia. Although many companies insist on pre-employment medicals, often including HIV testing, few have developed policies relating to test results. Some companies have instituted HIV education but there is a demand for this service to be available more widely. There has been a striking increase in mortalities in this working population, which seems likely to be related to HIV, although the cause of most deaths was not recorded.

AIDS Serodiagnosis↗
PubMed1995

Neurophysiologic assessment of urinary dysfunction in children with thoracic syringomyelia.

Isolated syringomyelia of the thoracic portion of the spinal cord is relatively uncommon. In children, signs and symptoms may involve only the urinary system. Five children who presented for evaluation of urinary tract dysfunction were found to have syringomyelia of the thoracic cord not associated with any other central nervous system abnormality on radiographic imaging. Each child underwent a complete neurologic examination and a complete electrophysiologic/urodynamic evaluation. One patient underwent surgical drainage of the syrinx due to progression of neurologic deficit, with slight improvement; three patients were treated pharmacologically to control the urinary dysfunction.

Child↗
PubMed1995

The concordance of pulsatile ultradian release of adrenocorticotropin and cortisol in male rhesus monkeys.

The ultradian release of ACTH and cortisol was investigated in six male rhesus monkeys (Macaca mulatta) with an intensive (2-min) blood-sampling procedure to investigate micropulsatile hormone secretory patterns. A sensitive and specific immunoradiometric assay was used to measure plasma ACTH concentrations. An objective pulse detection algorithm (Cluster) was used to assess the pulsatility of ACTH and cortisol release. The temporally coincident release of ACTH and cortisol was also examined. Venous blood samples were collected (over < 15 s) every 2 min for 120 min beginning at 1300 h. The number of ACTH peaks (3.2 peaks/h), interpulse intervals (19 +/- 2.4 min), and pulse amplitudes (9.7 +/- 1.6 pmol/L) in rhesus monkey were similar to corresponding measures of ACTH release in humans (3.3 peaks/h, 18 +/- 0.8 min, and 4.7 +/- 1.0 pmol/L, respectively). The number of cortisol peaks (2.3 peaks/h), interpulse interval (26 +/- 8.6 min), and other characteristics of pulsatile cortisol release were also determined. There was a 32.4% exact concordance of ACTH with cortisol peaks (11 of 34; P < 0.001). Fifty-six percent of ACTH peaks (19 of 34) were followed by a cortisol peak within 10 min (P < 0.02). There was a significant correlation between the ACTH and coincident cortisol pulse amplitudes (P < 0.0001). The amplitudes of ACTH peaks coincident with cortisol peaks at 0 min time lag were significantly higher than ACTH peaks not temporally coupled with cortisol peaks. Our data indicate that 1) high frequency, low amplitude micropulsatile ACTH secretion in rhesus monkeys is very similar to the high frequency ACTH rhythm in humans; 2) temporally concordant ACTH and cortisol release episodes may be amplitude coupled; and 3) an adequate incremental ACTH pulse amplitude may elicit a concurrent cortisol release episode from the adrenal cortex. These data suggest that the rhesus monkey is a potentially useful model for the study of neuroendocrine control of ACTH release.

Activity Cycles↗