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Biomedical subjects

A Mitchell

Publications and source records attributed to A Mitchell.

At least 199 records · Page 11Linked to original sources
PubMed1992

Regional localization of the selenocysteine tRNA gene (TRSP) on human chromosome 19.

The human selenocysteine tRNA gene (TRSP) has been localized on chromosome 19q13.2-->q13.3 by in situ hybridization and ordered with respect to other genes and anonymous DNA markers in this region by linkage analysis in the forty CEPH pedigrees. These loci span only 10 cM in males and about 30 cM in females. The order of the loci is cen ... D19S7-D19S9-D19S47-CYP2A-CYP2F1-APOC2++ +-(TRSP, CKM). CYP2B flanks the CYP2A and CYP2F1 loci, but it cannot be determined whether it is proximal or distal to the other two cytochrome P450 loci with respect to the centromere.

Chromosome Banding↗
PubMed1991

The regulation of hepatic lipase and cholesteryl ester transfer protein activity in the cholesterol fed rabbit.

Hepatic lipase (HL) and cholesteryl ester transfer protein (CETP) activities are both increased in the rabbit by cholesterol feeding. The in vivo regulation of HL and CETP were explored by examining changes in specific steady-state mRNA levels upon cholesterol feeding. On feeding rabbits cholesterol, HL activity increased 3-fold after 2 days and remained at 2.6-times the control value at 28 days. Specific rabbit HL mRNA levels were assessed by dot blot analysis of liver poly (A)+ RNA hybridized with the human HL cDNA. No significant changes in liver HL mRNA accompanied the increase in activity seen at days 2 and 7. At day 28 a modest rise of 46% was observed. A significant rise in CETP activity, evident 7 days after the commencement of cholesterol feeding, was maintained until day 28 when it was 2.4-times the control value. Using the human CETP cDNA as probe, rabbit liver CETP mRNA was also found to increase by day 7, rising to 3.7-times control by day 28. The strong temporal relationship between the rise in CETP activity and mRNA (r = 0.55, P = 0.02) suggests that the regulation of CETP may be primarily effected by the levels of specific mRNA. In contrast, the discordance between levels of lipase activity and mRNA suggests that post-transcriptional events may be more important in the regulation of HL in the cholesterol fed rabbit.

Animals↗
PubMed1991

Relationship of immunosuppression and serum lipids to the development of coronary arterial disease in the transplanted heart.

Coronary arterial disease in the cardiac allograft has emerged as the most serious long term complication of cardiac transplantation. The influence of patient-related and other potential risk factors on the development of coronary arterial disease at 1 year subsequent to cardiac transplantation was examined in 207 recipients. The mean age of donors in patients with coronary arterial disease was 28.5 +/- 9.5 years, compared to 22.6 +/- 7.9 years in patients without coronary arterial disease (P less than 0.01). Eight of the 35 patients who received immunosuppression by means of prednisone and azathioprine developed coronary arterial disease compared to 5 of the 172 patients who were treated with cyclosporin and azathioprine without routine oral prednisone (P less than 0.01). The relationship of levels of serum lipids to the subsequent development of coronary arterial disease was investigated in 95 patients with angiographically normal coronary arteries one year after cardiac transplantation. The cumulative probability of coronary arterial disease in those with total cholesterol greater than 5.8 mmol/l was 9.3% at 2 years (n = 40), 24.4% at 4 years (n = 21) and 45% at 4 years (n = 9) compared with 4.3% at 2 years (n = 45), 7.4% at 3 years (n = 32) and 14% at 4 years (n = 14) in those with a total cholesterol less than 5.8 mmol/l (P less than 0.05). Similarly, the incidence of coronary arterial disease was increased in patients with serum triglyceride greater than 1.4 mmol/l (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Low-dose simvastatin for the treatment of hypercholesterolaemia in recipients of cardiac transplantation.

There is increasing evidence that hypercholesterolaemia is an important contributor to the development of accelerated coronary arterial disease in the cardiac allograft. The optimal drug therapy of hypercholesterolaemia in recipients after cardiac transplantation, however, has not been defined. Simvastatin (an inhibitor of hydroxy-methyl glutaryl-coenzyme A reductase), at a dose of 10 mg/day, was administered to 12 recipients with serum total cholesterol greater than or equal to 7.8 mmol/l and serum triglyceride less than or equal to 4.5 mmol/l refractory to dietary measures during a follow-up period of 1-5 years after cardiac transplantation. All patients received maintenance doses of cyclosporin A and, in some instances, azathioprine and prednisolone. After 2 months treatment with simvastatin, serum total cholesterol was significantly reduced from 8.8 +/- 0.3 mmol/l (mean +/- SEM) to 5.5 +/- 0.5 mmol/l, P less than 0.001, low density cholesterol from 6.6 +/- 0.4 to 3.8 +/- 0.3 mmol/l, P less than 0.001 and triglycerides from 2.4 +/- 0.2 mmol/l to 1.8 +/- 0.2 mmol/l, P less than 0.005. These changes were maintained after a period of treatment of 8 months. Serum high density cholesterol, hepatic transaminase levels, serum creatinine, creatine kinase and cyclosporin A blood levels were not altered by treatment with simvastatin. It is concluded that, in this study group, low-dose simvastatin appears to be well tolerated and has favourable lipid modifying properties.

Adult↗
PubMed1991

Localization of a DNA segment encompassing four tRNA genes to human chromosome 14q11 and its use as an anchor locus for linkage analysis.

The chromosomal location of an 8.2-kb genomic fragment encompassing a cluster of four human tRNA genes has been determined by three complementary methods including Southern analysis of human/rodent somatic cell hybrids, in situ hybridization, and genetic linkage analysis. This tRNA cluster (TRP1, TRP2, and TRL1) is located near the T-cell receptor alpha (TCRA) locus at 14q11, and several RFLPs were detected at this site. These RFLPs and those at the TCRA and MYH7 (cardiac beta-MHC gene) loci have been used to type all informative members of the CEPH pedigrees. This has permitted ordering of these three gene loci and two anonymous probes (D14S26 and D14S25) in a 20-cM interval just below the centromere of chromosome 14. Based upon the chromosomal location and the polymorphisms at this site, one or more members of this gene cluster could serve as a useful anchor locus on chromosome 14.

Amino Acid Sequence↗
PubMed1991

Coronary reactivity to ergonovine--possible relationship to accelerated coronary arterial disease in cardiac transplant recipients.

Severe coronary artery spasm can occur in orthotopic cardiac transplant recipients. To investigate the possible mechanisms and relevance of coronary spasm to the subsequent development of coronary disease, the response of the coronary arteries to intracoronary ergonovine maleate was studied in 10 patients who had undergone orthotopic cardiac transplantation and were shown to have normal coronary arteries at angiography. Ergonovine in doses of 1, 5 and 10 micrograms was injected into the left coronary artery followed by 2 mg of isosorbide dinitrate. Proximal coronary artery luminal diameters were measured using automated computerized quantitative angiography of the left anterior descending (LAD) and circumflex (LCX) vessels. Five patients (responders) demonstrated a dose response curve to intracoronary ergonovine which was similar to that previously seen in non-transplant patients (mean percentage diameter change +/- SEM, -24.68 +/- 1.93 for LAD, -24.06 +/- 3.91 for LCX). The remaining five patients (non-responders) demonstrated a virtually flat dose response curve significantly different from that of the responders (P = 0.001 for LAD, P = 0.013 for LCX). Angiography after 2 years demonstrated significant coronary disease in four of the five responders to ergonovine. In contrast, the five non-responders to ergonovine continue to have no detectable disease by angiography.

Adult↗
PubMed1991

Response of recurrent giant cell myocarditis in a transplanted heart to intensive immunosuppression.

A 35-year-old man developed giant cell myocarditis resulting in severe congestive cardiac failure. He needed urgent orthotopic cardiac transplantation despite maximal doses of inotropes and augmentation with an intra-aortic balloon pump. The patient presented with rhythm disturbances and echocardiographically diminished ventricular function at subsequent follow-up. Biopsies then taken revealed recurrence of myocarditis in the transplanted heart. Investigations revealed no obvious cause for the myocardial granulomas nor any evidence of systemic granulomatous disease. The patient received, in addition to maintenance cyclosporin A and azathioprine, high doses of corticosteroids which resulted in complete resolution of the inflammatory process and no recurrence has been detected to date. This case shows that giant cell myocarditis can recur in the transplanted heart despite routine immunosuppression with azathioprine and cyclosporin A and that additional treatment with high dose corticosteroids is effective in causing regression of the inflammatory process.

Adult↗
PubMed1991

A scanning electron microscopic study of the human ovarian surface epithelium: characterization of two cell types.

The surface of the ovary has two types of epithelial cells. We have called these A and B cells and they are found in their own respective zones (A and B). To assess the scanning electron microscopic features of these cell types, 65 ovarian samples were collected from biopsies taken from 35 women with normal ovaries. Biopsies included developing follicles, corpora lutea and ovarian capsules. Type A cells were cuboidal and sometimes tall, with a mean diameter of 6.49 microns, and a mean density of microvilli of 6.48/microns 2. Type B cells, on the other hand, were flat squamous cells with broader and flat apices with mean diameters and microvillus density of 11.71 microns and 3.88/microns 2 respectively. The A and B zones were common to all surfaces including the distending follicle. Type A cells overlying the distended surface of a follicle had a mean diameter of 7.03 microns compared to a mean of 6.05 microns for the capsular surface. Type B cell diameters and the microvillus density of both types were more variable and did not differ significantly over any of the surfaces. We suggest that previous human studies which identified flattening of cells over the distending follicle were probably observing B cells. The relationship of the B zones to papillae and surface bridges on the ovarian surface, and the association of these with ovulation sites, suggests that B cells are probably metaplastic cells derived in response to chronic surface injury with ovulation.

Adult↗
PubMed1991

Intracranial fibromatosis.

Fibromatoses are uncommon infiltrative lesions affecting musculoaponeurotic structures, most often of the limbs and trunk. Lesions involving the cranial cavity are rare and require the same aggressive surgical management as elsewhere in the body. This case illustrates their clinical and neuroradiological features and underscores the necessity for aggressive resection to avoid recurrence. The literature is reviewed.

Adolescent↗
PubMed1991

Anaesthesia for a patient with giant axonal neuropathy.

Giant axonal neuropathy is a generalised disorder of cytoplasmic intermediate filaments which particularly involves the peripheral and central nervous systems. In this paper we describe a child with giant axonal neuropathy and discuss the anaesthetic management in the light of the pathology and physiology of the condition.

Anesthesia, General↗
PubMed1991

Fatal pneumococcal septicaemia associated with asplenia and isomerism of the right atrial appendages.

A 22 month old male infant with isomerism of the right atrial appendages (associated with a complete atrioventricular septal defect, double outlet right ventricle, and pulmonary valve stenosis) died from pneumococcal septicaemia after a 36 hour illness. He had not been given penicillin prophylaxis. Asplenia was confirmed at necropsy. In a survey of 50 paediatric cardiologists in the United Kingdom, 13 (33%) of the 40 (80%) who replied did not advise any prophylactic measures against pneumococcal infection in patients with isomerism of the right atrial appendages.

Heart Atria↗
PubMed1991

Oligonucleotide-primed in situ DNA synthesis (PRINS): a method for chromosome mapping, banding, and investigation of sequence organization.

Oligonucleotides were annealed to complementary sequences in fixed human metaphase chromosomes and extended with DNA polymerase. The newly synthesized fragments were labeled by incorporating bio-11-dUTP instead of TTP, and the sites of synthesis were detected by immunocytochemistry, using fluorochromes as the reporter molecules. We have obtained clear localization with oligonucleotides from alphoid (centromeric sequences), simple sequence (satellite) DNAs, a variety of Alu-dispersed repeated sequences, and oligonucleotides derived from the Tetrahymena and Trypanosoma telomere-specific sequences. The simple sequence and alphoid oligonucleotides gave results at least comparable to those obtained using the whole molecule as a probe for in situ hybridization, whereas the Alu oligonucleotides produced a diversity of results which depended on the absolute length and location of the oligonucleotide within the Alu sequence. The telomere-specific oligomers also produced a variety of results. The G-rich Trypanosoma oligomer and its complementary C-rich sequence produced strong telomeric signals and some interstitial signals on mouse chromosomes, but only weak telomeric signals on human chromosomes. The G-rich Tetrahymena oligomer produced detectable telomeric signals on human chromosomes. The technique appears to be a valuable extension of present tools for mapping and examining the organization of DNA sequences within chromosomes.

Animals↗
PubMed1991

Patterns of referral to a menopause clinic.

One hundred and fifty new patients attending the Menopause Clinic at Dulwich Hospital were questioned on their attitudes and fears about hormone replacement therapy and the perceived attitudes of their general practitioner. The majority of patients attending the clinic had initiated referral themselves and many had travelled from outside the health authority area in order to be seen. The waiting list for an appointment was often unacceptable. We conclude that specialist menopause clinics in teaching hospitals are unable to cope with the demand for information about the menopause and hormone replacement from post-menopausal women and suggest alternative means for providing this service.

Attitude of Health Personnel↗
PubMed1991

Transrectal ultrasound, digital rectal examination, and prostate-specific antigen: preliminary results of an early detection program for prostate cancer.

Three hundred and ninety eight self-referred men with no histories of prostate problems were followed once each year for up to four years to determine the feasibility of early prostate cancer detection by digital rectal examination, transrectal ultrasound, and prostate-specific antigen. Evaluation of prostate-specific antigen was based on a polyclonal level of normal of 2.6 nanograms per milliliter by the Yang assay. Biopsies were performed when indicated by either transrectal ultrasound or digital rectal examination. The overall cancer detection rate for the four year period was 6.3 percent. A 3:1 cancer detection advantage of transrectal ultrasound over digital rectal examination was shown. Transrectal ultrasound and prostate-specific antigen each detected 92 percent of the proven cancers, and were complementary when either test was normal, together detecting 100 percent of the cancers. Thirty two percent (8/25) of all cancers were detected by digital examination, with digital exam having no predictive power after two study years. Prostate-specific antigen as an initial screening test for early prostate cancer may identify a suspicious group, whom may further be evaluated by transrectal ultrasound and digital exam. Results of this study lend credibility to the large scale randomized screening study proposed by the U.S. National Institutes of Health in which prostate-specific antigen and digital rectal examination are to be used as initial tests for prostate cancer detection.

Aged↗
PubMed1991

Rabbit hepatic lipase cDNA sequence: low activity is associated with low messenger RNA levels.

We have investigated a possible mechanism for the reported low activity of hepatic lipase (HL) in the rabbit by cloning and sequencing the cDNA for rabbit HL and using the clone to quantify mRNA levels. A 1.6 kb cDNA clone was sequenced and found to encode the mature protein of 477 amino acids and 20 amino acids of the hydrophobic leader peptide. A high degree of amino acid sequence identity was demonstrated with human (81%) and rat (79%) HL. The putative active site was well conserved, and mutations reported to reduce activity in HL or lipoprotein lipase were not present in the rabbit sequence. The activity and mRNA levels were compared with those of the rat, an animal possessing relatively high HL activity. In post-heparin plasma of the rat, HL activity was nine times greater than in that of the rabbit (24.9 +/- 1.6 units per ml plasma, n = 5 vs. 2.7 +/- 0.1, n = 5, P = 0.0001). Comparison of mRNA levels was made by dot blot analysis of liver poly (A+) RNA obtained from each species and probed with either rabbit or rat HL cDNA, labeled to the same specific radioactivity. Specific HL mRNA levels were found to be nine times greater in the rat than in the rabbit (8.90 +/- 0.11 units, n = 5 vs. 1.00 +/- 0.01, n = 5, P = 0.0001). Thus, low hepatic lipase activity in the rabbit is associated with low mRNA levels, suggesting that the observed species difference in activity is due to differences in the level of mRNA.

Amino Acid Sequence↗
PubMed1991

Evaluation of graduating neonatal nurse practitioners.

To compare the knowledge and problem-solving, communication, and clinical skills of graduating neonatal nurse practitioners (NNPs) and pediatric residents, a cohort study was conducted in a 33-bed tertiary-level neonatal intensive care unit in a 400-bed teaching hospital affiliated with a faculty of health sciences. Participants were all (n = 10) NNP graduates from the first 3 years of the educational program and 13 (87%) of 15 second-year pediatric residents. One hundred multiple-choice questions and 20 radiographic slides were used to test knowledge; a semistructured oral examination tested problem-solving skills; three simulated interactions with parents tested communication skills; and seven simulated procedures tested clinical skills. Graduating NNPs scored similarly to the pediatric residents on the multiple-choice questions (difference -3.4%; 95% confidence interval [CI] around difference -9.7, 2.9), radiographs (difference -1.4%; 95% CI -11.5, 8.7), oral examination (difference 2.8%; 95% CI -11.1, 16.7), communication skills (simulated parents assessment: difference 0.8%; 95% CI -4.2, 5.7; expert observer assessment: difference 5.8%; 95% CI -2.8, 14.3), and clinical skills (difference 7.4%; 95% CI -5.5, 20.2). The NNPs about to graduate from their educational program showed knowledge and problem-solving, communication, and clinical skills equivalent to those of second-year pediatric residents and are thus likely to deliver comparable care in the clinical setting. The results support the adoption of the NNP role.

Clinical Competence↗