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Biomedical subjects

G Williams

Publications and source records attributed to G Williams.

At least 505 records · Page 28Linked to original sources

The effects of multiple amino acid substitutions on the polypeptide backbone of tuna and horse cytochromes c.

The cytochromes c provide a wide range of natural and mutant homologous proteins which may be used to study structure/function relationships in biological electron-transfer reactions. A description of the cytochrome c structure has been provided by high-resolution X-ray crystallography for the cytochromes from tuna, bonito, rice and yeast (Saccharomyces iso-1). Correlation of these structures with NMR parameters is necessary to confirm the structure of the protein in solution and to permit the routine characterisation of cytochromes c with novel sequences. We have previously reported a method based on the analysis of pseudocontact shifts which allowed us to compare the conformations of some amino acid side chains of tuna cytochrome c in solution and in the crystalline state. Here we report a comparison of the conformations of the polypeptide backbone of cytochromes c in proteins from tuna and horse, using the chemical shifts of the amide NH and C alpha H protons. It is found that the backbone conformation and hydrogen-bond network is closely conserved between these proteins, despite 19 amino acid substitutions. Appreciable differences occur in two regions, around Asn 31 and at the beginning of the 60s helix. Evidence for some rotational or translational motion of the C-terminal helix is also presented.

Amino Acid Sequence↗

Distinct binding sites for Ins(1,4,5)P3 and Ins(1,3,4,5)P4 in bovine parathyroid glands.

We utilized high specific activity, [32P]-labelled ligands to measure the binding of Ins(1,3,4,5)P4 and Ins(1,4,5)P3 to membranes prepared from bovine parathyroid glands. [32P]Ins(1,3,4,5)P4 bound rapidly and reversibly to parathyroid membranes, and the binding data could be fitted by the interaction of the ligand with two sites, one with Kd = 6.8 x 10(-9) M and Bmax = 26 fmol/mg protein and a second, lower affinity site, with Kd = 4.1 x 10(-7) M and Bmax = 400 fmol/mg protein. InsP5 was 10-20 fold less potent than InsP4, and Ins(1,3,4)P3 and Ins(1,4,5)P3 were nearly 1000-fold less potent in displacing [32P]Ins(1,3,4,5)P4. [32P]Ins(1,4,5)P3, on the other hand, bound to a single class of sites with Kd = 7.6 x 10(-9) M and Bmax = 34 fmol/mg. While the binding of [32P]Ins(1,4,5)P3 increased markedly on raising pH from 5 to 8, the binding of [32P]Ins(1,3,4,5)P4 decreased by 75% over this range of pH. Thus, [32P]-labelled Ins(1,3,4,5)P4 and Ins(1,4,5)P3 may be used to identify distinct binding sites which may represent physiologically relevant intracellular receptors for InsP3 and InsP4 in parathyroid cells.

Animals↗

Intraarticular corticosteroid injections: should we rest the joints?

To prevent damage in injected joints, it has been our policy to rest them for 48 hours. To test this assertion we randomized 30 rheumatoid arthritis (RA) patients (rest, no-rest). Results in 28 patients (63 joints: 27 rest and 36 no-rest) are presented. Joint evaluation was performed at baseline and at 48 hours (pain/tenderness, swelling and range of motion). Two analyses were conducted, the first included all joints, and the second only joint pairs. In both cases measurements at 48 hours were comparable for the rest and no rest group for both upper and lower extremity joints (pain/tenderness/swelling and range of motion). At a later follow up (average 10 months) there were no differences in any of the parameters examined. Our study suggests that rest is not essential for intraarticular corticosteroids to be beneficial, at least in an inpatient setting. The applicability of our data to an outpatient population remains to be determined.

Adrenal Cortex Hormones↗

A pharmacological evaluation of a new 3-month depot preparation of buserelin for prostatic cancer.

A new slow-release formulation of buserelin given as a 3-month depot injection was evaluated in four patients with advanced prostatic cancer. Treatment was maintained for a mean period of 15 months. Steady-state urinary buserelin concentrations were reached by the beginning of the 3rd week of treatment and maintained until the end of the 3rd month. Serum testosterone remained suppressed in the castrate range for the duration of the study. This preparation offers an advantage for the patient and clinician over existing methods of gonadotrophin-releasing hormone (GnRH) analogue administration and will enter further clinical trial.

Buserelin↗

A comparison of perinatal outcome in patients undergoing contraction stress testing performed by nipple stimulation versus spontaneously occurring contractions.

Perinatal outcomes were analyzed in 848 high-risk pregnancies managed with a prospective weekly contraction stress testing protocol. In 615 patients the last test was performed by a nipple stimulation protocol whereas 233 patients had sufficient spontaneous contractions for performance of the test. All patients were either delivered of their infants or admitted for delivery within 7 days of the last test. The results of the last test were compared to various perinatal outcome parameters. There was no significant difference in perinatal outcomes between the two groups.

Breast↗

Recurrent cardiac myxoma: the surgical implications of two distinct groups of patients.

15 consecutive cases where patients (11 female, 4 male) had undergone surgical excision of cardiac myxoma were reviewed. The 11 survivors were re-assessed by trans-oesophageal echocardiography and recurrent myxoma was detected in 2 patients. These two were the only patients who had originally presented with multiple myxomas. Analysis of these cases in conjunction with 26 previously reported cases of recurrence identifies two distinct groups of patients. In one group (12 cases, mean age 48.7 years) recurrence occurred at the site of previous excision, typically following the removal of a single septal myxoma by partial thickness excision. In the second group, which includes our two cases, (16 cases, mean age 30.6 years) recurrent myxoma was found distant to the site of previous excision, typically in younger patients who had multiple myxomas at original operation. These results suggest that 1) single myxomas should be removed by full thickness excision 2) in younger patients with multiple myxomas surgery should be as radical as possible.

Adult↗

The diet of steady drinkers with special reference to social variables.

The influence of a number of variables on the diets of 65 steady drinkers from alcohol rehabilitation units on Merseyside, United Kingdom was investigated. All drank principally beer or spirits. Social variables studied included age, sex, living alone or with others, employment status and socio-economic status. Alcohol-related variables included quantity consumed and preferred beverage. Dietary outcome was assessed in terms of the variety of foods and the number of meals eaten per week. Living alone proved by far the most important determinant of reduced diet. Spirit drinkers ate more meals than beer drinkers, but only if living with others. Increased alcohol consumption related modestly to fewer foods and meals being consumed. Drinkers living alone constitute a much larger proportion of those entering rehabilitation programmes in Queensland, Australia than in the United Kingdom. The present findings may help to explain the high incidence in Queensland of thiamin deficiency syndromes including the Wernicke-Korsakoff syndrome.

Adult↗

A controlled clinical trial on the cardiovascular effects of single doses of pseudoephedrine in hypertensive patients.

Twenty hypertensive patients received single oral doses of pseudoephedrine 60 mg or placebo in a double-blind, randomised, crossover trial. Systolic, diastolic, mean arterial blood pressure, and heart rate were measured at 5 min intervals for 30 min prior to and 210 min after the administration of pseudoephedrine or placebo. Statistically significant differences between the two treatments were observed with changes in systolic blood pressure (P less than 0.03) and heart rate (P less than 0.01) but not in diastolic (P greater than 0.03) and mean arterial blood pressure (P greater than 0.1). Minor differences in the number of reported side effects between the two treatments were not statistically significant.

Adult↗

Neonatal cranial ultrasonography as predictor of 2 year outcome of very low birthweight infants.

Real time ultrasound scans using an ATL 300C sector scanner with 5-7.5 MHz transducer were performed on days 1, 4, 7 and thereafter as clinically necessary on 153 consecutively discharged very low birthweight (VLBW) infants. One hundred and forty-six long-term survivors were assessed fully at 2 years. The prevalence of cerebroventricular haemorrhage (CVH) in these survivors was 34.2% (grade 1-21.2%; grade 2-4.8%; grade 3-3.4%; grade 4-4.8%), ventricular dilatation 19.9% (including 4.1% with ventriculoperitoneal shunt), and ischaemia 9%. Impairments at 2 years were classified as nil, mild, moderate, severe or multiply severe, based on the criteria of Kitchen et al. Overall, 120 infants (82.2%) were unimpaired and 6.2% had mild, 3.4% had moderate, 4.1% had severe and 4.1% had multiply severe impairment. The major factors associated with impairment were gestational age less than 28 weeks, birthweight less than 1000 g, vaginal delivery, respiratory distress syndrome, mechanical ventilation, pulmonary air leaks and CVH. When these factors were reanalysed in a logistic regression model for odds ratios, only CVH (P less than 0.005) and birth by spontaneous vaginal delivery (P less than 0.05) were significant. The prevalence of impairment was 11.4% with no CVH, 6.5% grade 1, 71% grade 2, 20.0% grade 3 and 100.0% grade 4 CVH. The sensitivity of CVH of grade 2 or greater as a screening test was 64.7% for impairment, 78.6% for cerebral palsy and 70% for severe intellectual handicap. The mean general quotient (GQ) (Griffiths) at 2 years for infants with CVH was 89.1, and 97.5 for those without CVH (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Brain Ischemia↗

New combination chemotherapy programme for bladder cancer.

Forty patients with either metastatic, post-radiotherapy recurrent, or poor prognosis locally advanced transitional cell carcinoma of the bladder were treated in a new combination chemotherapy programme with methotrexate, vinblastine, mitozantrone and JM8 (carboplatin); 33 patients were assessable for response. There were 9 complete responses (27%), 12 partial responses (36%) and 7 disease stabilizations (21%); 5 patients (15%) had progressive disease. The median duration of complete response has not been reached and is in excess of 9 months (range 4- greater than 18 months). This regimen was without significant toxicity and this is in contrast with M-VAC, which is thought to be currently the most effective treatment for urothelial cancer.

Adult↗

Blood group antigen expression in frozen sections of presenting bladder cancer: 3-year prospective follow-up of prognostic value.

Blood group antigen (BGA) expression was studied on frozen sections from the initial, presenting, transitional cell bladder cancers of 73 patients. Clinical follow-up was prospective and, after 3 years, 59 patients were available for assessment. Of 32 tumours that retained substantial BGA (BGA+ and BGA +/- ), 11 progressed. Of 27 tumours with less than 5% or undetectable BGA expression (BGA-), 14 did not progress. Of 24 pTa tumours, 17 had substantial BGA expression and 7 were BGA-; 5 patients progressed, 4 substantially BGA positive and 1 BGA-, all to category pT1; 15 tumours were category pT1, 7 substantially BGA positive and 8 BGA-; 7 patients progressed, 1 substantially BGA positive and 6 BGA-, all of whom died from bladder cancer; 20 were pT2 or deeper, 8 substantially BGA positive and 12 BGA-; 12 patients progressed, 6 substantially BGA positive and 6 BGA-, all of whom died from bladder cancer. Despite improved understanding of the biochemistry and techniques of detection of BGA, these results preclude the use of BGA determination as a guide to prognosis in individual transitional cell carcinoma, whether used alone or in combination with pT category.

ABO Blood-Group System↗

Change in glycoconjugate for the binding site of the lectin Ulex europeus 1 following malignant transformation of prostatic epithelium.

Immunoperoxidase techniques were used to detect Ulex europeus (UEA1) binding sites on benign and malignant prostatic epithelium. Formalin-fixed, paraffin-embedded (FFPE) and cryostat sections were compared. In benign epithelium, less than 10% of cells on FFPE sections but between 50 and 90% of cells on cryostat sections expressed UEA1 binding sites. In malignant epithelium, more than 90% of cells bound UEA1, irrespective of whether FFPE or cryostat sections were used. Lipid solvents are required for FFPE (but not cryostat) processing and may cause glycolipid extraction. Glycoproteins are not affected. These results suggest that the UEA1 binding site is predominantly glycolipid-based in benign prostatic epithelium but, following malignant transformation, becomes predominantly glycoprotein-based.

Aged↗

Bladder outflow tract obstruction and urinary retention from benign prostatic hypertrophy treated by balloon dilatation.

Forty-eight men with urodynamically proven bladder outflow tract obstruction (BOO) and 19 with retention secondary to benign prostatic hypertrophy were treated by balloon dilatation of the prostate as out-patients; 31 were dilated with 20 mm and 36 with 25 mm balloons. Of the 48 men with BOO, 37 had repeat cystometrograms at intervals ranging from 3 to 11 months after dilatation and 33 (89%) remained obstructed by urodynamic criteria. Of 6 who only had a peak flow rate assessment, 5 had a flow less than 12 ml/s. Of the 19 patients in retention only 3 were able to void and all are obstructed. Symptoms of hesitancy, poor stream, frequency and nocturia were improved in less than 50% of patients. No reliable correlation was found between objective response and balloon size, length of time of dilatation, prostate size or morphology, detrusor pressure or stability, or post-dilatation urethrogram appearances. Balloon dilatation to 25 mm is not adequate therapy for bladder outflow tract obstruction or urinary retention from prostatic hypertrophy.

Catheterization↗

Use of the "Correctaid" device in the management of impotence.

A series of 20 unselected patients with impotence of various aetiologies were given a custom fitted external erection assistance device, the Correctaid. They have been followed up for 14 months. Only 4 patients are still using the device regularly to attain satisfactory intercourse and a further 4 use it occasionally. This device is a useful, non-invasive alternative for the treatment of impotence in well selected, motivated patients and their partners.

Consumer Behavior↗