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Biomedical subjects

J Hill

Publications and source records attributed to J Hill.

At least 19 recordsLinked to original sources

Demonstration by FTIR that the bo-type ubiquinol oxidase of Escherichia coli contains a heme-copper binuclear center similar to that in cytochrome c oxidase and that proper assembly of the binuclear center requires the cyoE gene product.

Amino acid sequence data have revealed that the bo-type ubiquinol oxidase from Escherichia coli is closely related to the eukaryotic aa3-type cytochrome c oxidases. In the cytochrome c oxidases, the reduction of oxygen to water occurs at a binuclear center comprised of heme a3 and Cu(B). In this paper, Fourier transform infrared (FTIR) spectroscopy of CO bound to the enzyme is used to directly demonstrate that the E. coli bo-type ubiquinol oxidase also contains a heme-copper binuclear center. Photolysis of CO ligated to heme o at low temperatures (e.g., 30 K) results in formation of a CO-Cu complex, showing that there is a heme-Cu(B) binuclear center similar to that formed by heme a3 and Cu(B) in the eukaryotic oxidase. It is further demonstrated that the cyoE gene product is required for the correct assembly of this binuclear center, although this polypeptide is not required as a component of the active enzyme in vitro. The cyoE gene product is homologous to COX10, a nuclear gene product from Saccharomyces cerevisiae, which is required for the assembly of yeast cytochrome c oxidase. Deletion of the cyoE gene results in an inactive quinol oxidase that is, however, assembled in the membrane. FTIR analysis of bound CO shows that Cu(B) is present in this mutant but that the heme-Cu(B) binuclear center is abnormal. Analysis of the heme content of the membrane suggests that the cyoE deletion results in the insertion of heme B (protoheme IX) in the binuclear center, rather than heme O.(ABSTRACT TRUNCATED AT 250 WORDS)

Alkyl and Aryl Transferases

Soluble complement receptor type 1 ameliorates the local and remote organ injury after intestinal ischemia-reperfusion in the rat.

We examined the role of C activation in ischemia reperfusion injury by inhibiting C activation in a rat model of mesenteric arterial occlusion. In anesthetized rats, 60 min of mesenteric arterial occlusion was followed by 3 h of reperfusion. PBS alone or containing soluble C receptor 1 (3 or 6 mg) was administered i.v. Controls underwent laparotomy without ischemia. Relative serum C activities were assessed by hemolytic assay, neutrophil (polymorphonuclear leukocyte) sequestration by tissue content of myeloperoxidase (MPO) activity, intestinal mucosal injury by histologic grading, lung vascular permeability by the ratio of bronchoalveolar lavage to blood concentration of radiolabeled BSA, and endothelial cell injury was quantified by measurement of plasma factor VIII-related Ag. After reperfusion, PBS-treated animals had increased intestinal MPO (0.048 +/- 0.007 U/g) compared to sham (0.022 +/- 0.005 U/g (p less than 0.05)) and intestinal mucosal injury score (2.490 +/- 0.221) compared to sham (0.331 +/- 0.045 (p less than 0.05)). Treatment with 6 mg soluble C receptor 1 15 min before reperfusion reduced intestinal MPO (0.017 +/- 0.003 U/g (p less than 0.05)) and mucosal injury (1.733 +/- 0.168 (p less than 0.05)) compared to PBS control. PBS-treated animals also demonstrated increased lung MPO (0.314 +/- 0.025 U/g vs 0.085 +/- 0.018 in sham (p less than 0.05)) and increased lung permeability (bronchoalveolar lavage/blood cpm 11.32 +/- 1.35 x 10(-3) vs sham 2.22 +/- 0.19 x 10(-3) (p less than 0.05)). Treatment with 6 mg soluble C receptor 1 15 min before reperfusion or at reperfusion reduced the lung permeability (bronchoalveolar lavage/blood cpm 3.90 +/- 0.79 x 10(-3) and 5.08 +/- 0.75, respectively (both p less than 0.05)) compared to PBS control, but did not reduce lung MPO (0.342 +/- 0.031 U/g and 0.246 +/- 0.025), respectively. Treatment with sCR1 also reduced the release of factor VIII-related Ag, 5-day mortality, and C hemolytic activity. In this model, C is a major mediator of intestinal injury and extraintestinal injury.

Animals

Gonad protection in young orthopaedic patients.

OBJECTIVE: To determine whether gonad shields are correctly positioned on the pelvic radiographs of children with slipped capital femoral epiphysis. DESIGN: Retrospective study of radiographs taken of children treated by in situ pinning of slipped capital femoral epiphysis between 1 January 1983 and 31 December 1988. SETTING: Three teaching hospitals in north west England. PATIENTS: 32 patients with complete set of radiographs. RESULTS: An average of 10.8 anteroposterior pelvic radiographs plus 8.9 lateral hip radiographs had been performed per patient. Gonad shields had been completely omitted in 137 (40%) anteroposterior pelvic radiographs performed on the 32 patients at the time of completion of the study. In 100 (29%) the gonad shields were adequately protecting the gonads, but in 109 (31%) the gonad shields were not protecting the gonads due to incorrect positioning of the shield. The incorrect positioning of the gonad shields was more commonly found in girls than boys (64 vs 45; p less than 0.012), presumably because of the difficulty in determining gonadal position in relation to surface landmarks. Absence of gonad shields was also more commonly seen in girls (82 v 55; p less than 0.005), but this is not easily explained. CONCLUSIONS: Gonad shields are not protecting the gonads in a large percentage of anteroposterior pelvic radiographs (71%) because they have been omitted or inadequately placed. This avoidable excess radiation exposure to the gonads, combined with the inability to shield the gonads in lateral hip radiographs and the large number of radiographs performed, results in the gonads receiving a higher dose of radiation than may otherwise be the case, and may increase the potential for disease in the future offspring of these patients.

Adolescent

An improved means of faecal diversion: the trephine stoma.

Twenty-four patients in whom trephine stoma formation was performed over a 4-year period are described. This procedure permits the formation of an end ileostomy or colostomy without laparotomy. It is simple, rapid, safe and allows speedy recovery. It is widely applicable and previous abdominal surgery is no contraindication. The procedure was impossible in two patients who required laparotomy and in a third in whom a loop colostomy was created. Operation time was shorter and postoperative opiate requirements less than when laparotomy was undertaken for stoma formation. Follow-up (median 1 year) of 17 patients confirmed a low incidence of complications (two prolapses, one parastomal hernia) after trephine stoma formation. This procedure is recommended as the preferred method of ileostomy or colostomy formation when laparotomy is not otherwise indicated.

Adult

Preliminary evidence for a postsynaptic action of beta-bungarotoxin in mammalian skeletal muscle.

Two hours after treatment with beta-bungarotoxin (0.34-0.4 microM), when there was complete neuromuscular block, the peak contracture response to 50 microM succinylcholine was significantly reduced by about 35% in the mouse phrenic nerve-diaphragm preparation. Additionally, significant phospholipase A2 activity was detected on primary cell cultures from skeletal muscle which were incubated for 2 hr with concentrations of beta-bungarotoxin greater than or equal to 0.1 microM. Thus, beta-bungarotoxin appears to have pharmacologically and biochemically detectable postsynaptic actions in mammalian muscle systems.

Animals

Audiological, vestibular and radiological abnormalities in Kallman's syndrome.

Kallman's syndrome is a multifaceted congenital disorder with predominantly endocrine abnormalities. We have characterized the associated mixed hearing loss and identified consistent radiological evidence of abnormal temporal bone anatomy. Abnormal labyrinthine morphology is accompanied by a complete absence of response to vestibular stimulation with caloric or rotational chair testing. The endocrine abnormalities are correctable and Kallman's syndrome is a diagnosis worthy of consideration when assessing children with congenital hearing loss.

Adult

Neopterin measurement provides evidence of altered cell-mediated immunity in patients with depression, but not with schizophrenia.

Neopterin is a validated marker of the activation of cell-mediated immunity in a variety of disease states. We measured neopterin and creatinine concentrations in the plasma and urine of 22 schizophrenic and 26 depressed patients admitted acutely to hospital, and compared results with those in a large group of normal controls. Neopterin/creatinine ratios were normal in the schizophrenic patients, but significantly elevated in the plasma of depressed patients. In each diagnostic group, the use of psychotropic drugs before admission had no effect on the neopterin ratios observed. Our findings indicate altered cell-mediated immunity in depression.

Adolescent

Molecular weight changes in polymer erosion.

We report a study of the effects of polymer molecular weight on the erosion of polyanhydride copolymer matrices composed of 1,3-bis(p-carboxyphenoxy)-propane (CPP) and sebacic acid (SA) in aqueous solution. The erosion profile characteristically displays an induction period during which the erosion rate is relatively slow. The length of this period depends on the initial molecular weight of the polymer. The induction period may be characterized as a time during which a rapid decrease in polymer molecular weight occurs, the end of this period correlating with the time required for the polymer molecular weight to decrease to below a value of approximately 5000 (MW).

Decanoic Acids

Phthalylsulphathiazole in rheumatoid arthritis.

Sixteen patients with active rheumatoid arthritis were treated with phthalylsulphathiazole (4 g/day) over a period of 24 weeks. Although there was some statistically significant improvement in plasma viscosity, IgM, pain score, morning stiffness and summated change score, this was either intermittent or not maintained. Five patients withdrew from the trial before completion, four (25%) with non-serious adverse reactions and one patient from lack of efficacy; only one patient elected to remain on the drug beyond the 24-week period. Low free and total sulphathiazole serum concentrations were found, confirming that most of the drug remained within the gut. This investigation suggests, certainly at the dose used, that phthalylsulphathiazole does not have the properties of a second-line agent. Higher doses of the drug will not be ethically feasible.

Arthritis, Rheumatoid

Blockade of complement activation prevents local and pulmonary albumin leak after lower torso ischemia-reperfusion.

Lower torso ischemia and reperfusion leads to both local and remote tissue injuries. The purpose of this study was to assess the role of complement in mediating the local and remote microvascular permeability after bilateral hind limb tourniquet ischemia. Four hours of ischemia and 4 hours of reperfusion produced an increased skeletal muscle permeability index (muscle/blood 125I albumin ratio) of 2.90 +/- 0.35 compared with the index in nonischemic muscle of 0.25 +/- 0.02 (p < 0.01). Muscle wet-to-dry-weight ratio increased from 3.93 +/- 0.04 in sham to 5.55 +/- 0.09 in ischemic muscle (p < 0.0001). Lung permeability rose at 4 hours as indicated by the increased bronchoalveolar lavage (BAL)/blood 125I albumin ratio 4.36 +/- 0.41 x 10(-3) versus sham 2.64 +/- 0.28 x 10(-3) (p < 0.05) and neutrophil sequestration 0.28 +/- 0.02 U/g myeloperoxidase (MPO) versus sham 0.14 +/- 0.02 U/g (p < 0.001). Serum lytic activity of the classical but not the alternate complement pathway was reduced. The soluble complement receptor (sCR1) was used to inhibit complement activity and attenuated the increase in the permeability index after reperfusion in ischemic muscle 1.11 +/- 0.08 (p < 0.01) and reduced the lung BAL/blood 125I albumin ratio to sham levels 2.46 +/- 0.39 x 10(-3) (p < 0.05) at 6 mg/animal, without reducing the lung neutrophil sequestration, 0.24 +/- 0.02 U/g. The authors conclude that complement activation occurred during tourniquet ischemia and mediated permeability changes in the ischemic muscle and the lungs during reperfusion.

Albumins

Culture of human middle ear mucosal explants; mucin production.

Middle ear mucosal biopsies could be maintained in culture for up to 7 days, the longest time attempted in this study. Mucin biosynthesis and secretion were measured by incorporation of 14C-glucosamine. Three peaks of radioactivity were present when the dialysed medium was chromatographed. Peak I which accounted for about 10% of the total radioactivity had properties characteristic of mucin. The other two peaks were not characteristic of mucins. Labelled macromolecules excluded on Sepharose 2B were also present in the tissue. Autoradiography of the explants showed that the labelled glucosamine was concentrated in the epithelial layer. Morphometry demonstrated that 1-2% of the epithelial cell volume consisted of goblet cells. The proportionate incorporation of radioactivity into macromolecules increased with increasing epithelial cell volume. This system will allow assessment of factors implicated in the pathogenesis of otitis media with effusion and the study of the action of pharmacological agents on biosynthesis and secretion.

Autoradiography

Higher surgical training in Otolaryngology.

The views of the membership of the Association of Otolaryngologists in Training (all current UK Senior Registrars and Consultants in their first year of post) were sought on topical aspects of Higher Surgical Training. 80 members (72.3%) participated. The main points to emerge were that the intercollegiate exam is unpopular. 66% feel it is neither well suited to the developing career structure nor a good assessor of trainees, 80% of Senior Registrars for whom the exam is voluntary say they will not sit it, 66% have doubts about the confidentiality of the Specialist Advisory Committee (SAC) interview and 73% felt the need for a separate faculty for Otolaryngology at the Royal College of Surgeons.

Education, Medical, Continuing

Survey of satisfaction with care in a rheumatology outpatient clinic.

Consumer satisfaction is increasingly recognised by hospital administrators and health care providers as an important aspect of health care. A study was undertaken to investigate the satisfaction with care among patients with rheumatoid arthritis (RA) attending a rheumatology outpatient clinic at Leeds General Infirmary. The Leeds satisfaction questionnaire was developed and rigorously tested for reliability (Cronbachs alpha) and stability (test/retest). The Leeds satisfaction questionnaire was then completed by 70 patients with RA who had attended the Leeds General Infirmary on at least three previous occasions. The results showed that patients were, in general, satisfied with the care they received. The highest satisfaction scores were obtained on the scale for technical quality and competence of health professionals. The least satisfaction was accredited to the difficulty of unscheduled access to the clinic and the lack of continuity with the providers of care. The time spent in the waiting area before consultation was highlighted as the one aspect which caused the greatest dissatisfaction.

Adult

Repetitive strain disorder: towards diagnostic criteria.

Thirteen women (mean age 48.2 years; range 25-60 years) all of whom had developed musculoskeletal symptoms during employment in an industrial job with repetitive tasks were referred by their trade unions for adjudication on the cause of symptoms. One had rheumatoid arthritis. A study of the other 12 women provided an opportunity to document the natural history of repetitive strain disorder. Early symptoms of weakness were diffuse but were always relieved by rest. Several months later localisation of symptoms at a tendon, nerve, or enthesis could be predicted from the analysis of the action required in the particular repetitive task. Six of the 12 women required an operation several years later, thus providing histological confirmation of the presence of a lesion. Early loss of grip strength measured by a sphygmomanometer cuff compared with an unaffected control subject and improved by rest may be the most valuable sign in excluding compensation neurosis. The estimated prevalence of repetitive strain disorder defined by these strict criteria was at least 2% in conveyor belt workers.

Adult

Transitional cell carcinoma: a case for collaboration.

Urine samples from the greatest proportion of the numerical workload of most clinical microbiology laboratories. During the screening by microscopy, atypical cells were detected which did not conform to the normal cellular morphology found in urinary deposits. These specimens were referred to the Department of Cytopathology for a second opinion. From these referrals a small but significant number of previously undiagnosed transitional cell carcinomas were detected.

Aged

A Mac-1 antibody reduces liver and lung injury but not neutrophil sequestration after intestinal ischemia-reperfusion.

BACKGROUND: Intestinal ischemia and reperfusion (I/R) result in leukosequestration and injury to the liver and lungs. The adherence-dependent oxidative burst of neutrophils requires cell adhesion through the Mac-1 integrin. Neutrophil-mediated tissue injury may depend on this specific cell adhesion event. This study tests the effect of a Mac-1 (CD 11b) monoclonal antibody (MAb) (R17) on liver and lung injury after intestinal I/R. METHODS: After collaterals were ligated in anesthetized rats, the superior mesenteric artery was clamped for 60 minutes followed by 3 hours of reperfusion. Animals were treated with saline solution, R17, or nonspecific immunoglobulin M. Another nonischemic group of rats were sham controls. Lung and intestinal polymorphonuclear leukocyte sequestration was assessed by measurement of myeloperoxidase and lung permeability by bronchoalveolar lavage blood concentration ratio of 125I-labeled bovine serum albumin. RESULTS: At 3 hours of reperfusion lung and intestinal myeloperoxidase and lung permeability were increased. Treatment with R17 MAb did not reduce intestinal or lung myeloperoxidase but prevented increased lung permeability. Similarly, after treatment with saline solution, liver polymorphonuclear leukocyte sequestration increased after 3 hours of reperfusion, and serum alanine aminotransferase level rose eightfold. R17 MAb did not significantly reduce liver neutrophil sequestration; however, it reduced alanine aminotransferase level more than 50% when compared to saline solution controls. At 3 hours of reperfusion there was a leukocytosis (white blood cell count, 14.9 +/- 1.0 x 10(3)/mm3 vs 6.0 +/- 0.8 in sham [p less than 0.05]). The white blood cell count was unaffected by R17 MAb. CONCLUSIONS: These data indicate that a MAb to the neutrophil Mac-1 integrin reduces lung and liver injury after intestinal I/R but does not reduce lung or intestinal leukosequestration.

Animals

Leadership attributes identified by practicing occupational health nurses.

This study examined which theoretical approaches to leadership occupational health nurses perceive as most desirable. The trait approach dominates in North American research literature, with occupational health nurses favoring the more traditional leadership attributes of "visionary," "intellectually creative," and "strong linguistic ability." Australian occupational health nurses identified the managerial character traits of "being well informed," "good communication skills," and "objective decision maker" as most appropriate traits of good leaders. Occupational health nurses need to develop alternative leadership approaches to acquire effective political and organizational strategies in today's competitive environment.

Attitude of Health Personnel