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Biomedical subjects

G R Sutherland

Publications and source records attributed to G R Sutherland.

At least 343 records · Page 19Linked to original sources
PubMed1992

Mapping of the trichohyalin gene: co-localization with the profilaggrin, involucrin, and loricrin genes.

The chromosomal location of the gene encoding the human hair follicle protein trichohyalin has been determined by in situ hybridization. The human gene has been localized to the region 1q21.1-1q23 (probably 1q21.3) using a sheep trichohyalin cDNA probe. The genes encoding three other epithelial proteins, namely, profilaggrin, involucrin, and loricrin, are also located in the same region of chromosome 1, which, together with their similar gene and protein structures, suggests that the four proteins form a novel superfamily of epithelial structural proteins.

Chromosome Mapping↗
PubMed1992

Changes in left ventricular function and wall thickness in heart transplant recipients and their relation to acute rejection: an assessment by digitised M mode echocardiography.

OBJECTIVE: Assessment of changes in left ventricular diastolic function and wall thickness after heart transplantation to verify whether these changes predicted acute rejection assessed by endomyocardial biopsy. DESIGN: Follow up according to a predefined protocol of consecutive patients from the first week after transplantation. SETTING: Heart transplantation unit of the Thoraxcentre, University Hospital Rotterdam Dijkzigt, The Netherlands. PATIENTS: All 32 patients undergoing orthotopic heart transplantation from 1 January 1989 to 31 March 1990 were examined. Two were excluded from the analysis. Patients were treated with cyclosporin and low dose steroids. MAIN OUTCOME MEASURES: Data obtained by digitised M mode echocardiography were compared with the results of endomyocardial biopsy (Billingham classification). Mean values for left ventricular wall thickness, internal dimension, and their standardised rates of change and fractional shortening were determined from 4-6 consecutive expiratory beats. Mean values and individual trends during follow up were also investigated for each ultrasound variable. The results of these average values were compared with values in a group of 10 healthy volunteers. RESULTS: Median follow-up was 177 days (range 10-399). Two hundred and sixty three consecutive M mode studies were examined in relation to concurrent biopsy results. No significant differences were observed between the ultrasound variables at the time of moderate acute rejection (Billingham class 2, n = 37) and other biopsy classes (n = 226). Nor did changes in individual patients predict (moderate) acute rejection episodes. Twenty six of the 30 patients had an abnormal (slow) left ventricular relaxation pattern throughout follow up. CONCLUSIONS: Digitised left ventricular M mode echocardiography did not predict the presence of acute rejection. In most patients there was a persistent slow left ventricular relaxation pattern.

Acute Disease↗
PubMed1992

Myocardial dysfunction in patients infected with HIV: prevalence and risk factors.

OBJECTIVES: To determine the prevalence of and risk factors for myocardial dysfunction in HIV infection. SUBJECTS: 173 patients infected with HIV underwent echocardiography. 119 were current or previous injection drug users, 38 were homosexuals, 10 were haemophiliac patients, and six were heterosexual. MAIN OUTCOME MEASURE: Detection of impaired ventricular function. RESULTS: 26 patients with abnormalities of ventricular size or function or both were identified. The abnormality was (a) dilated cardiomyopathy in 13 patients (eight homosexuals, three drug users, and two haemophiliacs) with a mean CD4 count of 38 cells/mm3, which accords with end-stage disease (in addition, three patients were identified as having borderline impairment of left ventricular function); (b) left ventricular dilatation without loss of function in a further six patients; and (c) isolated right ventricular dilation in seven patients. Follow up echocardiograms were obtained in 71 patients, 18 of whom had myocardial dysfunction (103 echocardiograms, mean (SD) 2.5 (0.6) scans per patient, mean interval 200 (116) days, range 14-538 days). These showed that in four cases of isolated right ventricular dilatation, one of isolated left ventricular dilatation, and two with borderline left ventricular dysfunction myocardial function subsequently reverted to normal. There was no excess of exposure to zidovudine in the patients with myocardial dysfunction. Similarly, patients with myocardial dysfunction had no serological evidence of excess secondary infection with Toxoplasma gondii and cytomegalovirus. CONCLUSIONS: There was a high prevalence and wide range of myocardial dysfunction in HIV positive patients. Dilated cardiomyopathy was a feature of advanced HIV disease and affected all major risk groups for HIV infection. In contrast, isolated dilatation of either ventricle occurred at an earlier stage of HIV infection and, particularly in the case of the right ventricle, often was transient. Neither treatment with zidovudine nor infection with Toxoplasma gondii or cytomegalovirus seemed to be responsible for these findings.

Adult↗
PubMed1992

Experience with direct molecular diagnosis of fragile X.

The utility of the pfxa3 probe for direct molecular diagnosis of the fragile X (FRAXA) has been established. This probe detects amplification of an unstable DNA element consisting of variable length CCG repeats. The size of the amplified fragment is correlated with phenotype and was determined using PstI digested DNA in family members. In 35 families with the fragile X, there was correspondence in 183 cases between the presence of an amplified unstable element and the presence of the fragile X chromosome independently determined by cytogenetics, position in the pedigree, or linked DNA markers flanking the fragile X. There was also correspondence in 124 cases between the presence of the normal 1.0 kb PstI fragment and absence of the fragile X chromosome independently determined by linked flanking markers. Six additional families considered to be isolated cases of 'fragile X' had been diagnosed before recognition of FRAXD. The pfxa3 probe confirmed the cytogenetic diagnosis in three families, the other three being rediagnosed as non-fragile X. A further two families had consistent expression of a different folate sensitive fragile site, FRAXE, close to FRAXA but not associated with fragile X syndrome and not detectable with the pfxa3 probe. Subsequent referrals were received from additional family members or from members of new families for whom carrier status had not been predetermined by linked markers. Direct pfxa3 diagnosis for the 135 females within these 222 additional cases was confirmed by dosage analysis with the control probe pS8.(ABSTRACT TRUNCATED AT 250 WORDS)

Artifacts↗
PubMed1992

Localization of the human GM-CSF receptor beta chain gene (CSF2RB) to chromosome 22q12.2-->q13.1.

The gene for the beta-chain of the human GM-CSF receptor (CSF2RB) has been mapped to chromosome 22 by PCR analysis of a series of human x rodent somatic cell hybrids. In situ hybridization to normal human chromosomes and two translocations involving chromosome 22 and the chromosome expressing the rare fragile site FRA22A place the gene in the region 22q12.2-->q13.1, proximal to the fragile site.

Chromosomes, Human, Pair 22↗
PubMed1992

Chromosomal location of the human transketolase gene.

The gene encoding the human transketolase enzyme (TKT) was localized by fluorescence in situ hybridization to normal and FRA3B human chromosomes. Southern blot analysis of a series of human x mouse and human x hamster hybrid cell lines confirmed this localisation. TKT maps to 3p14 and distal to FRA3B, localizing TKT to 3p14.3.

Animals↗
PubMed1992

Forebrain ischemia in diabetic and nondiabetic BB rats studied with 31P magnetic resonance spectroscopy.

In spontaneously diabetic BB rats, the effect of chronically maintained blood glucose levels on the degree of energy failure and brain pH change during an ischemic insult, and on subsequent recovery after reperfusion, was studied with in vivo 31P magnetic resonance spectroscopy. Short duration forebrain ischemia (10-min carotid occlusion plus hypotension of 50 mmHg) was induced in diabetic and nondiabetic male BB rats whose blood glucose levels were maintained with insulin. Spectra were obtained in 1-min blocks before, during, and for 1 h after ischemia. Before ischemia, hypoglycemic (blood glucose less than 3 mM) diabetic rats had an increased Pi peak intensity, with no significant pH change, compared with other groups. During ischemia, the rate and extent of hydrolysis of high-energy phosphate metabolites (as measured by an increase in Pi) decreased, and the severity of tissue acidosis increased as preischemia blood glucose concentration increased. Among hyperglycemic BB rats, similar ischemia-induced changes were found for subgroups with blood glucose levels of 13.7 +/- 1.2 and 20.3 +/- 0.6 mM, in keeping with the known decrease in hexose binding sites associated with chronic hyperglycemia. Decline in PCr level during ischemia was not significantly different between groups. With reperfusion, both Pi and pH values rapidly returned to preischemia values. PCr levels, however, did not recover in hyperglycemic diabetic animals, with the degree of residual impairment dependent on the preischemia glucose level. Results suggest that optimal management of diabetes may lessen the degree of injury within the ischemic penumbra in diabetic patients who suffer a stroke.

Analysis of Variance↗
PubMed1992

Magnetic resonance imaging and 31P magnetic resonance spectroscopy study of the effect of temperature on ischemic brain injury.

Transient forebrain ischemia was induced in rats whose brain temperature was 31, 33, 35, 38, or 40 degrees C. The development of regional injury was followed using magnetic resonance (MR) imaging, with the ultimate extent of neuronal injury quantified histopathologically. Animals in the hypothermic groups showed minimal changes in MR images over 4 days; normothermic animals showed intensity enhancement attributed to progressive edema developing in the striatum and, later, in the hippocampus. Ischemia at 40 degrees C resulted in widespread edema formation by 1 day post-ischemia; animals in this group did not survive beyond 30 hours. Histopathological analysis at 4 days (1 day for the hyperthermic group) post-ischemia showed that neuronal damage in the normothermic group was confined to the hippocampus and striatum. Minimal damage was found in the hypothermic groups; damage in the hyperthermic group was severe throughout the forebrain. There were no differences in the pre-ischemia 31P MR spectra for the different groups. During ischemia, the increase in intensity of the Pi peak and the fall in tissue pH increased with temperature in the order hypothermic less than normothermic less than hyperthermic group of animals. Post-ischemia energy recovery was similar in all groups, while pH recovered more rapidly in hypothermic animals.

Animals↗
PubMed1992

Characterization of a deletion at Xq27-q28 associated with unbalanced inactivation of the nonmutant X chromosome.

We report the results of studies on the characterization of the mutation associated with marked unbalanced expression of the mutant X chromosome in a karyotypically normal girl with Hunter disease (mucopolysaccharidosis type II). Southern analysis of DNA extracted from somatic cell hybrids containing only the mutant X chromosome showed deletion of the Xq27.3-q28 loci: DXS297 (VK23AC), DXS293 (VK16), FRAXA (pfxa3), DXS296 (VK21A), and the 3' end of the iduronatesulfatase (IDS) gene. The flanking loci--DXS52 (St14-1), DXS304 (U6.2), and DXS369 (RN1)--were intact. On the basis of these results, we concluded that the mutation was a simple deletion extending a maximum of 3-5 cM to the centromeric side of the IDS gene. Both Southern analysis of DNA from somatic cell hybrids, using short segments of IDS cDNA, and PCR of reverse-transcribed RNA from cultured skin fibroblasts indicated that the telomeric terminus of the deletion was localized to a region near the middle of the coding sequences of the gene.

Autoradiography↗
PubMed1991

Transesophageal echocardiographic monitoring of interventional cardiac catheterization in children.

Transesophageal echocardiography was used prospectively in 22 children scheduled for interventional cardiac catheterization (9 with pulmonary valvuloplasty, 5 with aortic valvuloplasty, 1 with pulmonary angioplasty, 2 with aortic angioplasty, 2 with patent ductus arteriosus occlusion and 3 with Mustard baffle dilation) to determine its potential value as a monitoring technique. The patients ranged in age from 0.9 to 14.6 years (mean 5.4) and in weight from 9.5 to 49.2 kg (mean 21.1). Studies were completed in all patients without complications. Preintervention studies provided important new information in two patients, leading to cancellation of the planned procedure. Major contributions of transesophageal monitoring included 1) a real time assessment of catheter placement across either atrioventricular valve and the aortic valve during balloon valvuloplasty; 2) immediate assessment of aortic valve and aortic wall morphology during balloon dilation; and 3) detailed morphologic and hemodynamic information together with enhanced catheter guidance during Mustard baffle dilation. After pulmonary valvuloplasty, partial chordal rupture of the tricuspid valve was documented in one patient. In two patients, balloon catheter position was modified according to the transesophageal findings. The assessment of changes in pulmonary valve morphology and transcatheter occlusion of a patent ductus arteriosus was not enhanced by single-plane transesophageal monitoring. Pulsed wave Doppler studies contributed additional information in the assessment of immediate hemodynamic changes after interventional procedures. Transesophageal echocardiography is a new important guiding and monitoring technique during interventional cardiac catheterization procedures in children. It can provide additional real time imaging information, immediate identification of complications and assessment of hemodynamic changes.

Adolescent↗
PubMed1991

Hereditary unstable DNA: a new explanation for some old genetic questions?

Fragile X syndrome, associated with the fragile X chromosome, is the most common cause of familial mental retardation. The condition is characterised by a heritable DNA sequence that consists of an abnormal number of CCG repeats, and which is unstable in both mitosis and meiosis. We suggest that such heritable unstable DNA sequences could be present in other parts of the genome and that these might explain a number of genetic events that are not well understood in terms of classic genetic mechanisms. Such poorly explained observations include anticipation, incomplete penetrance, variable expression, and possibly imprinting, variegation, and multifactorial inheritance.

Chromosome Fragility↗
PubMed1991

Mapping of DNA instability at the fragile X to a trinucleotide repeat sequence p(CCG)n.

The sequence of a Pst I restriction fragment was determined that demonstrate instability in fragile X syndrome pedigrees. The region of instability was localized to a trinucleotide repeat p(CCG)n. The sequence flanking this repeat were identical in normal and affected individuals. The breakpoints in two somatic cell hybrids constructed to break at the fragile site also mapped to this repeat sequence. The repeat exhibits instability both when cloned in a nonhomologous host and after amplification by the polymerase chain reaction. These results suggest variation in the trinucleotide repeat copy number as the molecular basis for the instability and possibly the fragile site. This would account for the observed properties of this region in vivo and in vitro.

Base Sequence↗
PubMed1991

Surgery for Ebstein's anomaly: the clinical and echocardiographic evaluation of a new technique.

Ten consecutive patients (age range 4 to 44 years, mean 22) underwent surgical repair of Ebstein's anomaly by vertical plication of the right ventricle and reimplantation of the tricuspid valve leaflets. No patient died during or after operation. Intraoperative postbypass echocardiography documented a good result in nine patients but severe tricuspid regurgitation in one patient, who then underwent prosthetic valve replacement during a second period of cardiopulmonary bypass. Two of four patients who had had right ventricular papillary muscle dysfunction in the early postoperative period showed improved papillary muscle function with concomitant reduction of tricuspid regurgitation 6 months later. All patients were evaluated clinically and by echocardiography 2 to 23 months later. All patients showed clinical improvement, seven by one functional class and three by two classes. All were in sinus rhythm. The mean cardiothoracic ratio decreased by 6% (p less than 0.05). On bicycle ergometry performed in six patients, peak oxygen consumption exceeded 20 ml/kg per min in five. Tricuspid regurgitation diminished in eight patients (by three grades in two patients, by two grades in five and by one grade in one patient); it remained unchanged in two. Comparison of preoperative and postoperative pulsed Doppler flow velocities across the pulmonary valve showed an increase in the peak velocity of flow across the valve (mean 83 +/- 14 versus 97 +/- 11 cm/s, p less than 0.005) and a decrease in the time to peak velocity (mean 130 +/- 16 versus 91 +/- 23 ms, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗