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Biomedical subjects

N Carter

Publications and source records attributed to N Carter.

At least 91 records · Page 5Linked to original sources
PubMed1995

Lack of association between angiotensinogen polymorphism (M235T) and cerebrovascular disease and carotid atheroma.

Genetic influences in cerebrovascular disease (CVD) may act either independently or by predisposing to, or modulating, the effect of risk factors such as hypertension. Factors involved in the pathogenesis of atherosclerosis, thrombosis and vasoconstriction are important in CVD. The angiotensinogen gene has recently been linked with essential hypertension in affected sibships and a particular polymorphism in exon 2 of the angiotensinogen gene, a threonine to methionine substitution at position 235 (M235T), has been associated with pre-eclampsia and hypertension. In this study we examined the relation of M235T polymorphism to cerebrovascular disease and carotid atheroma in 100 consecutive Caucasian patients with internal carotid artery territory ischaemia (TIA or stroke), presenting to a carotid ultrasound service. Forty five age-matched controls (mostly patients' spouses) were also studied. Hypertension was defined as current treatment with anti-hypertensive agents, or SBP > 160 mm Hg or DBP > 95 mm Hg. Twelve of 100 cases (12%) and eight of 45 controls (12%) were homozygous for the T235 allele. T:M allele ratios were 0.34:0.66 in cases and 0.34:0.66 in controls. There was no relation between the polymorphism and either internal carotid stenosis or common carotid artery intima-media thickness. In the cases, mean percentage internal carotid artery stenosis was TT 18.3 (SD 18.7)%, MT 38.0 (27.1)% and MM 36.8 (30.2)%. Mean intima-media thickness was TT 0.87 (0.18) mm, MT 0.95 (0.34) mm and MM 0.88 (0.23) mm. There was no relation between the polymorphism and hypertension (TT 11 of 100 cases, six of 45 controls).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1994

Isolation of the gene for McLeod syndrome that encodes a novel membrane transport protein.

McLeod syndrome is an X-linked multisystem disorder characterized by abnormalities in the neuromuscular and hematopoietic systems. We have assembled a cosmid contig of 360 kb that encompasses the McLeod gene locus. A 50 kb deletion was detected by screening DNA from patients with radiolabeled whole cosmids, and two transcription units were identified within this deletion. The mRNA expression pattern of one of them, designated as XK, correlates closely to the McLeod phenotype. XK encodes a novel protein with structural characteristics of prokaryotic and eukaryotic membrane transport proteins. Nucleotide sequence analysis of XK from two unrelated McLeod patients has identified point mutations at conserved splice donor and acceptor sites. These findings provide direct evidence that XK is responsible for McLeod syndrome.

Amino Acid Sequence↗
PubMed1994

Ventricular expression of basic fibroblast growth factor gene after orthotopic cardiac transplantation.

We studied the ventricular expression of basic fibroblast growth factor (bFGF) at the mRNA level in normal and transplanted human hearts as a direct measure of local bFGF gene expression. By Northern blot hybridization with a human bFGF cDNA probe, mRNA transcripts 7.5, 3.5, and 2.0 kb for bFGF were detected in both normal and transplanted hearts. Densitometric analysis of the transcripts after normalization for RNA loading revealed a 2-fold increase in the transplanted compared with the normal hearts. Slot blot hybridization of the ventricular RNA showed a significant increase in bFGF mRNA level in the transplanted over the normal hearts (P < 0.01) and was independent of hemodynamic parameters and immunosuppressive drugs. These results provide unequivocal evidence that the human heart is a site of bFGF production as demonstrated by the presence of bFGF mRNA. The increased ventricular expression of bFGF gene after heart transplantation may be of importance in the mediation of growth and repair of myocardial injury.

Adolescent↗
PubMed1994

Angiotensin-converting enzyme genotype is not associated with endothelial dysfunction in subjects without other coronary risk factors.

The DD genotype is a polymorphism of the angiotensin-converting enzyme (ACE) gene, and is associated with a significantly increased risk of myocardial infarction. As endothelial dysfunction is an important event in both early atherogenesis and late atherosclerosis, we hypothesised that the adverse effect associated with the ACE/DD genotype might be mediated via endothelial damage. Using high resolution ultrasound, we studied the brachial arteries of 184 subjects aged 15-73 (mean 38 +/- 14) years, who were all normotensive, non-diabetic lifelong non-smokers. Arterial diameter was measured at rest, during reactive hyperaemia (with flow increase causing endothelium-dependent dilation) and after sublingual glyceryl trinitrate (GTN, an endothelium-independent vasodilator). The ACE genotype was determined in each case by DNA amplification; 49/184(27%) had DD, 89 (48%) had ID and 46 (25%) had II genotype. Flow-mediated dilation (FMD) was 8.5% +/- 3.9% in the DD, 7.8% +/- 4.1% in the ID and 7.8% +/- 4.1% in the II subjects (P = NS). GTN-induced dilation was also similar in the 3 groups. On multivariate analysis, endothelium-dependent dilation was inversely related to age (r = -0.33, P < 0.001), vessel size (r = -0.41, P < 0.001) but not ACE genotype (r = 0.002, P = 0.97). The ACE genotype is unrelated to endothelium-dependent dilation in the systemic arteries of clinically well adults. This suggests that the risk associated with this polymorphism may be mediated by other mechanisms.

Adolescent↗
PubMed1994

The expression of carbonic anhydrases II and IV in the human pancreatic cancer cell line (Capan 1) is associated with bicarbonate ion channels.

Human pancreatic ductal cells of the Capan 1 cell line differentiate progressively during growth. After the exponential growth phase, the cells elongate and become polarized with their apical poles covered by microvilli and separated from the basolateral pole by tight junctions. In this stationary phase, they form domes, which are thought to result from the exchange of water and electrolytes. In this study, we demonstrated, using patch-clamp techniques, that HCO3- ions exit via the g350 high conductance anionic channel we observed recently at the Capan 1 cell surface. This g350 channel was thought to be either a Cl-/HCO3- antiport or a simple HCO3- channel. The stilbene derivatives 4-acetamido-4 isothiocyano-2-2'-disulfonic acid (SITS) and 4,4' diisothiocyano stilbene-2,2' disulfonic acid (DIDS) reduced both the number of domes and the Cl- and HCO3- flux through the g350 channel. Moreover, using histochemical, immunocytochemical and biochemical methods we showed that Capan 1 cells express a specific pattern of carbonic anhydrases (CA). Two types of CA were detected: the CA II isozyme mainly localized in the cytoplasm, but also found beneath the inner leaflet of the apical plasma membrane, and the CA IV isozyme localized on the outer leaflet of the apical plasma membrane and microvilli. Their molecular masses were 30 (CA II) and 55 kDa (CA IV), respectively. They were expressed continuously during the exponential growth phase, although their activity increased greatly during the stationary phase. Inhibition of dome formation by acetazolamide indicated the existence of a direct relationship between dome formation and CA. Characteristic structures with a central electron-dense core surrounded by a light halo were observed on the surface of cell membrane using histochemical and immunocytochemical methods. These structures were thought to represent a channel, corresponding possibly to CA IV. Our observations suggest that Capan 1 cells, despite their neoplasic transformation, produce HCO3- ions in the same way as normal human pancreatic ductal cells. Capan 1 cells in culture may therefore represent a suitable model for studying pancreatic duct HCO3- secretion at the cellular and molecular levels.

Acetazolamide↗
PubMed1994

Effect on patient management of a weekend 'on-call' nuclear medicine service.

The Nuclear Medicine Department at Kent and Canterbury Hospital operates a limited weekend on-call service staffed on a rota basis by a technician, a nurse and a doctor. Following a review of the service over a 2-year period, a prospective study was carried out to analyse the workload of the on-call service from August 1991 to July 1992. The aim was to assess the impact of the service on patient management and examine the cost implications. Sixty-two scans were performed during the year (38 Saturday, 22 Sunday, 2 Bank Holiday) of which 52 were ventilation/perfusion (V/Q) lung scans. The study examined the reports on the scans and the subsequent course of treatment and changes in patient management. For V/Q lung scans, anticoagulation therapy was changed in 13 cases as a result of the scan report. Of the lung scans showing low probability of pulmonary emboli, four patients were discharged on the day of the scan and a further eight within 48 h. The total cost of the on-call service (staff and consumables) was 6020 pounds, i.e. less than 100 pounds per patient and less than 2% of the departmental budget. The low cost and high number of changes in patient management indicate a reasonable cost-benefit ratio.

Cost-Benefit Analysis↗
PubMed1994

Angiotensin-1 converting enzyme (ACE) polymorphism in patients presenting with myocardial infarction or unstable angina.

A deletion/insertion polymorphism in the ACE gene has been reported previously as a potent factor for myocardial infarction. We have tested the frequency of the deletion (D) allele of the ACE gene in 308 consecutive patients admitted to coronary care with chest pain. The gene frequencies were compared with those of 348 controls recruited from the London area. Of 108 Caucasian patients with myocardial infarction, the DD genotype was found more frequently than the combined DI and II genotypes (Chi-square, chi 2 = 5.07, 2P = 0.024). The overall D gene frequency was higher in myocardial infarction patients (125 of 216, 58%) than in controls (347 of 696, 49.9%) (chi 2 = 3.79, 2P = 0.052). In contrast, the DD genotype and D allele frequencies in patients with unstable angina were similar to those found in our normal population. A nonsignificant difference in allele frequency between myocardial infarction and unstable angina patients was observed but the small numbers of subjects studied precludes a more formal comparison. Since unstable angina and myocardial infarction represent a spectrum of coronary thrombosis, it is possible that the DD genotype favours the development of myocardial infarction, perhaps through the presence of higher serum ACE concentrations.

Aged↗
PubMed1993

Ultrastructural heterogeneity in undifferentiated bronchial carcinoma.

Electron microscopy is often suggested as a useful aid to the classification of light microscopically undifferentiated bronchial malignancies, features such as dense-core vesicles, desmosomes or tonofilaments, and microacini, allowing their designation as endocrine, squamous, or adenocarcinomas respectively. However, there is no reason to suppose that the heterogeneity of malignant bronchial tumours so often apparent by light microscopy or on immunolabelling might not occur at the ultrastructural level too. Extensive sampling of all deposits from eight subjects coming to necropsy with undifferentiated bronchial carcinoma revealed ultrastructural features of glandular and squamous differentiation to be widespread and often to occur together, although dense-core vesicles were not seen in any of the tumours studied. Heterogeneity was present within individual tumour deposits and particularly between different deposits of those tumours which had disseminated, such that any ultrastructural diagnosis would have been significantly influenced by sampling. Such variation should be borne in mind when ultrastructural features are used to classify bronchial malignancies.

Bronchial Neoplasms↗
PubMed1993

Brain natriuretic peptide and fluid volume homeostasis--studies during cardiopulmonary bypass surgery.

Brain natriuretic peptide (BNP) is a recently identified cardiac ventricular hormone with diuretic, natriuretic and vasorelaxant properties. The aim of our study was to examine whether serial changes in endogenous levels of BNP were associated with fluid volume homeostasis following cardiopulmonary bypass. We studied nine patients undergoing elective cardiac surgery for the repair of cardiac abnormalities requiring cardiopulmonary bypass. Urinary levels of cyclic guanosine monophosphate (cGMP), sodium, urine output, fluid balance, and plasma levels of BNP, aldosterone, plasma renin activity (PRA) and central venous pressure (CVP) were measured before, during and after cardiopulmonary bypass. Basal pre-operative plasma BNP levels were highly elevated in all nine patients with cardiac abnormalities. During bypass, pre-operative levels of BNP, urinary cGMP and plasma aldosterone decreased significantly (p < 0.05), whereas pre-operative levels of urinary sodium and PRA were slightly reduced. During recovery following bypass levels of urinary cGMP, sodium, PRA and aldosterone returned to basal pre-operative values, whereas post-operative levels of plasma BNP were found to be three-fold below basal pre-operative levels. CVP (4.3 +/- 0.2 mmHg) during the onset of bypass increased significantly (p < 0.05) at the end of bypass (9 +/- 0.3 mmHg) followed by a modest increase post-operatively (10 +/- 0.4 mmHg). After operation only BNP had a significant correlation with urine output (r = -0.82, p < 0.02) and net fluid balance (r = -0.84, p < 0.01), whereas urinary cGMP, PRA and aldosterone all exhibited a non-significant correlation with urine output.(ABSTRACT TRUNCATED AT 250 WORDS)

Aldosterone↗
PubMed1993

Ventricular expression and circulating levels of immunoreactive dynorphin in heart transplant recipients.

1. Dynorphin, an endogenous opioid peptide, acts on specific kappa-opioid receptors in the rat heart for the local regulation of atrial natriuretic peptide release. No known study has examined the expression of dynorphin in the human heart. 2. In the present study a specific radioimmunoassay technique was used to determine ventricular expression of dynorphin at the peptide level in endomyocardial biopsy specimens and in plasma obtained from 13 heart transplant recipients. Ventricular biopsy specimens collected from 10 patients without cardiac complications during necropsy (less than 24 h from time of death) and plasma samples from 10 normal healthy subjects were used as controls. 3. The immunoreactive level of ventricular dynorphin was higher in heart transplant recipients (mean +/- SEM 141 +/- 32 pg/mg of soluble protein, range 7-573 pg/mg of soluble protein, P < 0.001) than in control subjects (16 +/- 3 pg/mg of soluble protein, 2-34 pg/mg of soluble protein). The plasma concentration of immunoreactive dynorphin was also higher (P < 0.001) in heart transplant recipients (mean +/- SEM 14 +/- 1 pg/ml, range 5-39 pg/ml) than in normal healthy subjects (7 +/- 0.4 pg/ml, 5-10 pg/ml). No relationship was observed between ventricular and plasma levels of dynorphin. 4. These results show that immunoreactive levels of dynorphin in plasma and ventricle are increased after heart transplantation, suggesting a possible pathophysiological role for dynorphin in the heart.

Adolescent↗
PubMed1993

Cardiac transplantation affects ventricular expression of brain natriuretic peptide.

OBJECTIVE: The aim was to examine the ventricular expression of brain natriuretic peptide (BNP) in the transplanted human heart. METHODS: Serial right ventricular biopsies (n = 68) and plasma samples (n = 68) were obtained for measurement of BNP and atrial natriuretic peptide (ANP) from 14 orthotopic cardiac transplant recipients from 1-74 weeks after transplantation. Right ventricular specimens (n = 10) were also obtained from normal hearts during necropsy as controls. RESULTS: Mean ventricular BNP in cardiac transplant recipients was higher (p < 0.05) than in normal hearts, at 13531(SEM 2244) pg.mg-1 soluble protein (range 3232-109448) v 56(11) pg.mg-1 (range 16-91). Ventricular BNP and ANP values were correlated (r = 0.57, p < 0.05). Plasma BNP concentrations were higher (p < 0.05) than plasma ANP concentrations, at 202(16) pg.ml-1 (range 84-655) v 100(12) pg.ml-1 (range 8-484), and were raised (p < 0.05) in comparison with normal plasma BNP concentrations of 20(1.8) pg.ml-1 (range 10-23). Mean ventricular BNP was correlated with time after transplant (r = 0.72, p < 0.05, n = 68) and with mean plasma BNP (r = 0.80, p < 0.05, n = 14). There was no significant relationship between BNP levels and intracardiac or systemic blood pressure, or prednisolone dose (0.1-0.3 mg.kg-1.d-1). The increase in ventricular BNP with time after transplant was not explained by cardiac rejection assessed from histology, and plasma BNP was not significantly increased during rejection episodes. CONCLUSIONS: High levels of BNP are synthesised and secreted by the transplanted human ventricle, and the transplanted ventricle may be an important source of circulating BNP. The significant positive association between ventricular BNP and time after transplant suggests a possible self compensatory mechanism or functional adaptation of the transplanted heart which may be beneficial to ventricular function.

Adolescent↗
PubMed1993

Ventricular expression of atrial natriuretic peptide after orthotopic cardiac transplantation.

In order to determine if atrial natriuretic peptide is produced by the human ventricle after transplantation, specimens were obtained from 54 separate right ventricular endomyocardial biopsies from 14 transplant recipients (age range 10-19 years) and were analyzed with simultaneous plasma samples. Radioimmunoassay techniques were used to determine plasma and tissue levels of atrial natriuretic peptide in each biopsy specimen, and blot hybridizations with the atrial natriuretic peptide c deoxyribonucleic acid probe were performed once for each patient. Mean plasma levels of atrial natriuretic peptide were obtained from the right ventricle (106 +/- 12 pg/ml); there was a positive correlation with end diastolic pressure (r = 0.7, P < 0.0001). Plasma levels, however, were not significantly increased during rejection episodes. Atrial natriuretic peptide was detectable in all ventricular biopsy specimens--mean 989 +/- 164 pg/mg soluble protein. Mean tissue level during rejection episodes was 1163 +/- 17 and following treatment of rejection was 411 +/- 147--however, this difference was not significant (P = 0.55). In 6 patients biopsied within 1 month of transplantation initial myocardial levels were significantly higher than those obtained at the following biopsy (P < 0.05). Despite these initially high tissue levels no correlation was found with time posttransplantation. Ventricular tissue levels positively correlated with systolic ventricular pressure, r = 0.3, P < 0.05, but there was no significant correlation with other hemodynamic parameters. The normalized atrial natriuretic peptide messenger ribonucleic acid signal from the slot blot hybridization was 59 +/- 6 mm (peak height of signal intensity) range 20-110 mm. The expression of atrial natriuretic peptide gene was also confirmed by Northern blot analysis. The ventricular messenger ribonucleic acid signal contained a single hybridizing band of approximately 920 nucleotides. Thus, we have demonstrated that atrial natriuretic peptide production by the human ventricle is independent of innervation. The consistent atrial natriuretic peptide gene expression and detection by radioimmunoassay in apparently healthy ventricles was unexpected but may reflect the use of immunosuppressive drugs, or perhaps subclinical graft dysfunction.

Adolescent↗
PubMed1993

Deletion analysis maps ocular albinism proximal to the steroid sulphatase locus.

We describe a pedigree in which four male members are affected by a contiguous gene abnormality involving the short arm of the X chromosome (Xp22.32). Bivariate flow cytometry of lymphoblastoid cell lines from two of these individuals and a normal male showed a 6-7 megabase deletion in affected males, and high resolution chromosomal G-banding of an obligate heterozygote showed the deletion to reside in the Xp22.32 region. Affected members had X-linked ichthyosis due to steroid sulphatase deficiency, Kallmann's syndrome, but no ocular albinism. In two out of four affected individuals studied, there was unilateral renal agenesis. Deletion analysis using the Xp22.32 markers MIC2, DXS31, DXS 89, GMGX9, DXS278, DXS143, and DXS9 showed that the deletion extended from DXS31 to DXS143 (inclusive). The absence of ocular albinism in this pedigree shows conclusively that the X-linked ocular albinism gene resides proximal to the DXS143 locus. Further, the inconstant association of unilateral renal agenesis with X-linked Kallmann's syndrome, even when the latter is caused by a complete deletion of the gene, suggests that the absence of the X-linked Kallmann gene can be compensated in renal development.

Albinism, Ocular↗
PubMed1993

Carbonic anhydrase III in obese Zucker rats.

Proteins from 5- to 7-wk-old lean and obese Zucker rats were separated by one-dimensional sodium dodecyl sulfate (SDS) and two-dimensional SDS-isoelectric focusing-polyacrylamide gel electrophoresis. Laser densitometry revealed an obesity-related decrease in the concentration of a 28-kDa cytosolic adipocyte protein, the most abundant protein in adipocytes from lean Zucker rats. Microsequencing revealed the identity of this protein to be carbonic anhydrase III (CA III). The identity and obesity-related decrease was further confirmed using isoform-specific antisera and CA III enzyme activity measurements made by 18O mass spectrometry. Immunoblotting studies also revealed that CA III is present in at least two charge isoforms in adipocytes. Our data indicate that lean Zucker rat adipocytes may represent the richest source of CA III in nature (24% of the cytosolic protein content). An obesity-related decrease in both the concentration and activity of CA III was observed in two lipogenic tissues, liver and white fat, but not in soleus muscle. Adipocyte CA III activity was no longer depressed when hyperinsulinemic obese rats were made insulin deficient by streptozotocin injection. This suggests that the obesity-related decrease in CA III may be related to the hyperinsulinemia as well as to the insulin hyperresponsiveness that adipocytes from obese Zucker rats of this age display.

Adipose Tissue↗