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Biomedical subjects

A Mitchell

Publications and source records attributed to A Mitchell.

At least 181 records · Page 10Linked to original sources
PubMed1993

The effect of the HMG-CoA reductase inhibitor simvastatin and of cholestyramine on hepatic apolipoprotein mRNA levels in the rat.

We have administered the hypolipaemic drugs simvastatin and cholestyramine to rats, both separately and together, to determine whether drug-induced changes in plasma apo lipoprotein levels occur through regulation of hepatic genes coding for apolipoproteins (apos) AI, AIV, E and B. Cholestyramine alone had little effect on either the plasma levels of the apolipoproteins studied or their hepatic mRNA levels. However, simvastatin, either alone or in combination with cholestyramine, produced marked changes in both of these parameters. While simvastatin plus cholestyramine lowered mRNAs for apo AIV, apo E and apo B by 50%, 37%, and 55%, respectively, the treatment resulted in an increase of 150% in apo AI mRNA. This combined drug treatment caused a lowering in plasma concentration of all four apolipoproteins which failed to reach significance with apo E. Relative to controls, the values decreased to 83 +/- 14% for apo AI, 67 +/- 8% for apo AIV and 73 +/- 15 for apo B. An important novel finding of the present study, was that hypolipaemic drugs caused the apo B mRNA levels in rat liver to decrease. Previous reports have shown that although dietary fat or hormones caused marked changes in the concentration of circulating lipoproteins, they failed to alter apo B mRNA content. We suggest that the synthesis of apo B is subject to both pre- and post-translational regulation.

Animals↗
PubMed1993

Spermatid nucleus of Megaselia scalaris Loew (Insecta, Diptera, Phoridae): a study using anti-histone antibodies, scanning electron microscopy, and a centromere-specific oligonucleotide.

The structure of elongated spermatid nuclei was examined in the fly Megaselia scalaris using indirect immunofluorescence with anti-histone antibodies, scanning electron microscopy, and in situ hybridization with a centromere-specific oligonucleotide. The immunofluorescence experiments showed that, in keeping with the situation in most animals, histones are hyperacetylated prior to their displacement from the nucleus in the course of spermiogenesis. Scanning electron microscopy revealed that grooves run parallel to the long axis of the spermatid nuclei. The chromatin is segmented into blocks lateral to the grooves. This finding most probably indicates that the chromatin is not yet maximally condensed at this stage. The retarded chromatin condensation may be correlated with the export of somatic histones from the nucleus. The location of the centromeres could not be identified using scanning electron microscopy, but in situ hybridization showed that a centromere-specific oligonucleotide mapped to the central or close to the central areas within the spermatid nucleus. Possibly, the chromosomes are extended and arranged parallel to the long axis of the spermatid nucleus.

Animals↗
PubMed1993

Neurofibromatosis type 1 gene product (neurofibromin) associates with microtubules.

The neurofibromatosis type 1 (NF1) gene was recently identified by positional cloning and found to encode a protein with structural and functional homology to mammalian and yeast GTPase-activating proteins (GAPs). Using antibodies directed against the NF1 gene product, a protein of approximately 250 kDa was identified and termed neurofibromin. Double-indirect immunofluorescent labeling with anti-neurofibromin and anti-tubulin antibodies demonstrates that neurofibromin associates with cytoplasmic microtubules. Immunoblotting of microtubule-enriched cytoplasmic fractions, using antibodies generated against neurofibromin, shows that neurofibromin copurifies with microtubules. When portions of neurofibromin are expressed in Sf9 insect cells they associate with polymerized microtubules; furthermore, the critical residues for this interaction reside within the GAP-related domain of neurofibromin. The unexpected association of neurofibromin with microtubules suggests that neurofibromin is involved in microtubule-mediated intracellular signal transduction pathways.

3T3 Cells↗
PubMed1993

Core-peripheral temperature gradient in children: does it reflect clinically important changes in circulatory haemodynamics?

Following open heart surgery, changes in core and peripheral skin temperature and changes in the core-peripheral temperature gradient were measured in 10 children. These were correlated with changes in cardiac index, systemic vascular resistance index, mean arterial pressure and urinary output. During the study intervals, which lasted 1 h each, no changes in medical management were made. Using Spearman's rank correlation, only a change in central venous pressure was found to correlate with a change in the core-peripheral temperature gradient. We conclude that a change in the core-peripheral temperature will give valuable information about the patient's intravascular volume.

Blood Pressure↗
PubMed1993

Symptomatic intradural adrenal adenoma of the spinal nerve root: report of two cases.

The second and third cases of an adrenal adenoma involving the intraspinal space, a rare location for a lesion that occurs rather commonly at a variety of extraneural sites, are reported. The first patient, a 16-year-old girl with a 3-month history of radicular pain, was found to have an intradural, extramedullary mass arising on a spinal nerve root. Its resection resulted in cure. The second patient, a 63-year-old woman with a 10-month history of low back pain with radiation to both lower extremities, had a similar mass arising from one of the nerve roots of the cauda equina. In both cases, ultrastructural examination of these demarcated, oncocytic, lipid-rich lesions demonstrated abundant smooth endoplasmic reticulum and mitochondria with tubular cristae. The presence of steroidogenic enzymes was noted on immunohistochemical examination. The literature is reviewed, as is the differential diagnosis of these rare lesions.

Adenoma↗
PubMed1993

Cortical blindness and seizures possibly related to cisplatin, vinblastine, and bleomycin treatment of ovarian dysgerminoma.

Ovarian dysgerminoma is the most common ovarian malignancy in young women. Conservative treatment is indicated in the reproductive-age woman who wishes to preserve childbearing capacity. This case report describes a patient with ovarian dysgerminoma who underwent chemotherapy with a cisplatin-vinblastine-bleomycin regimen that resulted in serious toxic complications--including cortical blindness and seizures--that were transient in nature. Although current chemotherapy regimens have dramatically improved the overall survival of women with germ-cell tumors, there are toxic complications such as those demonstrated in this report, and toxicity must be balanced against presumed benefit.

Adult↗
PubMed1993

Infusion of atherogenic lipoprotein particles increases hepatic lipase activity in the rabbit.

Hepatic lipase plays a key role in the turnover of potentially atherogenic lipoprotein remnants and in determining the relative distribution of high density lipoprotein (HDL) particle size subclasses. Rabbits fed a cholesterol-enriched diet have been found to accumulate potentially atherogenic chylomicron remnants and beta-very low density lipoprotein (beta-VLDL) and show a rapid increase in liver and postheparin plasma hepatic lipase activity. To determine whether the particles that accumulate during cholesterol feeding are a stimulus for this increase in hepatic lipase activity, we infused normal chow-fed rabbits with a chylomicron remnant plus beta-VLDL-enriched plasma fraction isolated from rabbits fed 0.5% cholesterol-supplemented chow. The infusion of this plasma fraction for 4 h increased hepatic lipase activity up to 2.9-fold over control rabbits and resulted in a loss of larger sized HDL particles consistent with the action of hepatic lipase. The increase in activity was significantly correlated with the concentration of infusate phospholipid, unesterified cholesterol, and esterified cholesterol, but not with the infusate triglyceride concentration. The change in the plasma cholesterol concentration of recipient rabbits, which reflects the degree of lipoprotein accumulation in these rabbits, was also significantly correlated with the change in hepatic lipase activity. However, a chylomicron remnant and beta-VLDL-depleted fraction of plasma from cholesterol-fed rabbits did not increase hepatic lipase activity. Furthermore, triglyceride presented as an artificial lipid emulsion (Intralipid) was not able to stimulate hepatic lipase activity, although triglyceride is a substrate for hepatic lipase.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Maxepa versus bezafibrate in hyperlipidemic cardiac transplant recipients.

Accelerated coronary artery disease is the most serious obstacle to long-term survival in cardiac transplant recipients. Lipid abnormalities are found frequently in these patients, and there is growing evidence that even minimally increased levels of cholesterol and triglycerides contribute to the development of accelerated coronary artery disease. However, the optimal lipid-lowering therapy after cardiac transplantation has not been defined. In an open, randomized study, the efficacy and safety of bezafibrate (400 mg/day) and fish oil (Maxepa) (10 g/day) for 3 months were compared in 87 cardiac transplant recipients with serum total cholesterol > 6.5 or triglycerides > 2.8 mmol/liter, or both. After 1 month, bezafibrate reduced total cholesterol by 13%, low-density lipoprotein cholesterol by 20% and apolipoprotein B by 13%. It also increased apolipoprotein A1 and high-density lipoprotein cholesterol by 12 and 20%, respectively, and significantly reduced fibrinogen at 3 months. Maxepa had no significant effect on these variables, but was as effective as bezafibrate in reducing triglycerides (36 and 31%, respectively). Both drugs increased lipoprotein (a) to a similar extent, and bezafibrate significantly increased serum creatinine. These results suggest that bezafibrate has better lipid-, apolipoprotein- and hemostatic modifying properties than does Maxepa, but its potentially adverse effect on renal function needs further investigation.

Apolipoprotein A-I↗
PubMed1992

Antibodies to defined histone epitopes reveal variations in chromatin conformation and underacetylation of centric heterochromatin in human metaphase chromosomes.

Unfixed metaphase chromosome preparations from human lymphocyte cultures were immunofluorescently labelled using antibodies to defined histone epitopes. Both mouse monoclonal antibody HBC-7, raised against the N-terminal region of H2B, and rabbit serum R5/12, which recognizes H4 acetylated at Lys-12, gave non-uniform labelling patterns, whereas control antibodies against total histone fractions H4 and H1 produced homogeneous fluorescence. HBC-7 bound approximately uniformly to the bulk of the chromosomes, but the major heterochromatic domains of chromosomes 1, 9, 15, 16 and the Y showed significantly brighter fluorescence. Serum R5/12 indicated an overall reduction in acetylation of H4 in metaphase chromosomes compared with interphase nuclei, although some specific chromosomal locations had considerably elevated acetylation levels. Acetylation levels in the major heterochromatic domains appeared extremely low. To investigate further the differences noted in heterochromatin labelling, metaphases from cultures grown in the presence of various agents known to induce undercondensation of the major heterochromatic domains were similarly immunolabelled. Decondensed heterochromatin no longer exhibited higher than normal immunofluorescence levels with HBC-7. The higher resolution afforded by "stretching" the centromeric heterochromatin of chromosomes 1, 9 and 16 confirmed the low level of H4 acetylation in these domains. We consider the implications of these observations in relation to chromatin conformation and activity.

Acetylation↗
PubMed1992

The organisation of repetitive DNA sequences on human chromosomes with respect to the kinetochore analysed using a combination of oligonucleotide primers and CREST anticentromere serum.

The spatial relationship between the families of repetitive DNAs present at the centromeres of human chromosomes and the position of the kinetochore was examined by combining immunocytochemistry with the PRINS oligonucleotide primer extension technique. Heterochromatic domains were decondensed with 5'-azacytidine to facilitate this study. Using this approach our results clearly show that the alphoid DNA sequences are closely associated with the kinetochore of human chromosomes. Simple-sequence satellite DNAs occupy separate, non-overlapping domains within the centromere. These two major families are separated by a third, relatively low-copy repetitive DNA family, SAU-3A. Pulse-field gel electrophoresis was employed to analyse the centromeric domain of human chromosome no. 9 in more detail and the results although preliminary support the conclusions drawn from the immunocytochemistry/PRINS approach.

Antibodies, Antinuclear↗
PubMed1992

Dipyridamole vasodilator response after human orthotopic heart transplantation: quantification by oxygen-15-labeled water and positron emission tomography.

To assess coronary vasodilator reserve after orthotopic heart transplantation, regional myocardial perfusion was measured with oxygen-15-labeled water and dynamic positron emission tomography in 14 cardiac allograft recipients who were not experiencing rejection and who had no angiographic evidence of epicardial coronary sclerosis 15 to 73 months (mean +/- SD 43 +/- 19) after transplantation (group I). Twelve normal men with an average age of 31 years (group II) served as a control group. Regional perfusion was measured at rest and after the intravenous administration of 0.6 mg/kg body weight of dipyridamole. Rest regional myocardial blood flow was homogeneously distributed throughout the left ventricle and was significantly higher in transplant recipients (mean 1.16 +/- 0.26 ml/g per min [range 0.8 to 1.73] than in normal subjects (mean 0.85 +/- 0.13 ml/g per min [range 0.57 to 0.99]; p = 0.001) as was rest heart rate-systolic blood pressure product (rate-pressure product 11,255 +/- 2,540 vs. 7,073 +/- 1,306; p less than 0.001). After dipyridamole, perfusion in the transplant recipients was homogeneous and slightly lower (2.73 +/- 1.03 vs. 3.40 +/- 1.09 ml/g per min; p = NS), whereas rate-pressure product was slightly higher (12,179 +/- 2,266 vs. 10,885 +/- 1,895; p = NS) than the value in normal subjects. Dipyridamole vasodilator response (dipyridamole/rest myocardial blood flow) ranged from 1.23 to 4.92 (mean 2.50 +/- 1.13) in group I and from 2.65 to 5.45 (3.97 +/- 0.89) in group II (p = 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

A stereological study of the human ovarian surface epithelium.

The surface of the ovary has been found to be composed of two types of epithelial cells called A and B cells which are found in their own respective zones, the A and B zones. A quantitative study was undertaken to determine the mean cell volumes and cell ultrastructure. Ovarian biopsies were taken from six women and A and B zones, having been identified by scanning electron microscopy, were re-embedded for transmission electron microscopy. Stereological measurements using point sampled intercepts were made on vertical sections and showed that B cells are significantly larger than A cells. The volume weighted mean cell volumes of the A and B cells were 237.3 microns 3 and 676.8 microns 3 respectively. The volume fractions of the nucleus and mitochondria were similar in the two cell types. Although the vesicle content of each type was similar, a large variation between cases made the interpretation difficult. The stereological tools used in this study proved to be easy and efficient estimators of surface cell ultrastructure and give an important direction for ultrastructural research.

Biopsy↗
PubMed1992

Definition of an advanced nursing practice role in the NICU: the clinical nurse specialist/neonatal practitioner.

We surveyed 655 health professionals affiliated with tertiary level neonatal intensive care units in Canada and the United States to define an expanded role for nurses in neonatology and to determine the educational requirements for the role. The role, comprising advanced clinical practice, educational, research, and administrative responsibilities, is a blend of nurse practitioner and clinical nurse specialist activities. Based on survey findings, a neonatal stream within the existing Master of Health Sciences program at McMaster University was developed. To date, 15 clinical nurse specialists/neonatal practitioners (CNS/NPs) are employed in five neonatal intensive care units in Ontario and other related institutions. A randomized trial to evaluate these individuals is in progress.

Humans↗
PubMed1992

Perforated peptic ulcer in the Hunter region: a review of 174 cases.

A review of 174 consecutive patients admitted with a diagnosis of perforated peptic ulcer to eight Hunter Region hospitals during 1979-86 is presented. Among the female admissions, the proportion of patients greater than 70 years of age was twice that in males. One-third of all perforations were in females who accounted for two-thirds of all perforated gastric ulcers. Multivariate analysis revealed that perforations located in the stomach and older age were both significant independent variables adversely affecting outcome following surgery. In contrast, shock at presentation and delay in operating were not statistically significant independent risk factors.

Adolescent↗
PubMed1992

Limited value of the resting electrocardiogram in assessing patients with recent onset chest pain: lessons from a chest pain clinic.

OBJECTIVE: To evaluate a clinic set up specifically to assess patients with recent onset chest pain, particularly those presenting with a normal resting electrocardiogram. DESIGN: Retrospective review of case notes. SETTING: Cardiac department of a tertiary referral cardiothoracic centre. PATIENTS: 250 consecutive patients with recent onset chest pain seen within 24 hours of general practitioner referral. OUTCOME MEASURES: Clinical diagnosis and management. RESULTS: 40% of patients were seen within seven days of the onset of symptoms. Twenty seven per cent had non-cardiac symptoms and could be discharged while 60% were considered to have cardiac pain. Sixty six patients (26%) were admitted directly from the clinic and 48 of these underwent coronary angiography within three weeks. Seventy patients (28%) have so far undergone intervention (angioplasty or coronary artery surgery), 22 within one month of presentation. One hundred and nine patients (44%) presented with a normal resting electrocardiogram, 21 of whom were considered to have unstable angina. Forty one of these patients were investigated of whom 37 were found to have significant coronary disease and 26 have undergone intervention. CONCLUSIONS: This experience highlights the inadequacy of a routine electrocardiogram reporting service in patients with recent onset of chest pain. An alternative facility offering immediate and complete cardiac assessment produced patient benefit with early diagnosis and intervention. Investigation of these patients, however, accounted for 5% of cardiac catheterisation laboratory throughput; this was a significant additional and unscheduled workload.

Adult↗