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Biomedical subjects

A Cook

Publications and source records attributed to A Cook.

At least 109 records · Page 6Linked to original sources
PubMed1991

Pathologic spectrum of malformations of the tricuspid valve in prenatal and neonatal life.

The morphologic spectrum of malformations of the tricuspid valve in 14 fetal and 5 neonatal heart specimens is described. Echocardiography during fetal life had revealed the valvular malformations along with dilation of the right-sided chambers of the heart and atrioventricular (AV) valve incompetence. This functional impairment reflected either Ebstein's malformation (10 cases) or dysplasia of valve leaflets having a normal junctional attachment (9 cases). The right atrium and right ventricle were markedly enlarged, and heart weight was increased to 181% (median) and 179% (median) in the groups with Ebstein's malformation and valvular dysplasia, respectively. In contrast, lung weight was in the lower range of normal, showing a decrease of 67% (median) in patients with Ebstein's malformation and of 43% (median) in those with valvular dysplasia. One ventricular septal defect and six atrial septal defects were noted in each group. Severe obstruction at the level of the pulmonary valve was seen in 40% of the group with Ebstein's malformation and in 66% of those with valvular dysplasia. The most important factor in the particularly poor prognosis in these patients is the incompetence of the tricuspid valve, leading to right atrial enlargement and subsequent pulmonary hypoplasia. No significant difference was found between the pathologic features of fetal and neonatal hearts and no features that might have prompted the valve to become regurgitant during fetal life were identified.

Abnormalities, Multiple↗
PubMed1991

Double-outlet right ventricle: morphologic demonstration using nuclear magnetic resonance imaging.

Sixteen patients with double-outlet right ventricle, aged 1 week to 29 years (median 5 months), were studied with a 1.5 tesla nuclear magnetic resonance (NMR) imaging scanner. Two-dimensional echocardiography was performed in all patients. Thirteen patients underwent angiography, including nine who underwent subsequent surgical correction. Three patients underwent postmortem examination. Small children and infants were scanned inside a 32 cm diameter proton head coil. Multiple 5 mm thick sections separated by 0.5 mm and gated to the patient's electrocardiogram were acquired with a spin-echo sequence and an echo time of 30 ms. A combination of standard and oblique imaging planes was used. Imaging times were less than 90 min. The NMR images were technically unsuitable in one patient because of excessive motion artifact. In the remaining patients, the diagnosis of double outlet right ventricle was confirmed and correlated with surgical and postmortem findings. The NMR images were particularly valuable in demonstrating the interrelations between the great arteries and the anatomy of the outlet septum and the spatial relations between the ventricular septal defect and the great arteries. Although the atrioventricular (AV) valves were not consistently demonstrated, NMR imaging in two patients identified abnormalities of the mitral valve that were not seen with two-dimensional echocardiography. In one patient who had a superoinferior arrangement of the ventricles, NMR imaging was the most useful imaging technique for demonstrating the anatomy. In patients with double-outlet right ventricle, NMR imaging can provide clinically relevant and accurate morphologic information that may contribute to future improvement in patient management.

Angiography↗
PubMed1991

Blunting of neuroendocrine responses to infusion of L-tryptophan in women with perimenstrual mood change.

The neuroendocrine response to L-tryptophan infusion was measured at two stages of the menstrual cycle, premenstrually and postmenstrually, in 13 women with and 13 women without premenstrual depression (the MC and NMC groups respectively). Previous studies have shown that in non-depressed women, this challenge test results in an increase in circulating prolactin and growth hormone. In depressed women both responses are blunted. In this study the growth hormone and cortisol responses were smaller in the MC group than the NMC group on both occasions. The prolactin response was blunted premenstrually compared with postmenstrually in both groups. These findings suggest that women who experience premenstrual depression may have neuroendocrine abnormalities throughout the cycle. The neurotransmitter abnormalities reflected in these altered endocrine responses appear to interact with neuroendocrine changes that normally occur premenstrually resulting in a vulnerability to depression at that phase of the cycle.

Adolescent↗
PubMed1991

Receptors mediating tachykinin-induced contractile responses in guinea-pig trachea.

1. The classification of tachykinin receptors in the guinea-pig trachea has been investigated. This was of interest because, from previous studies, it was not clear whether the guinea-pig trachea contains either a mixture of NK1 and NK2 receptors or, alternatively, a single type of novel tachykinin receptor. 2. In the present study, the guinea-pig trachea was contracted by tachykinin agonists selective for NK1 receptors (substance P methylester (SPOMe) and GR73632) or NK2 receptors (GR64349) but not NK3 receptors (senktide). 3. Against SPOMe and GR73632, the NK1 antagonist, GR71251, behaved as a reversible competitive antagonist having apparent affinity (pKB 7.05 vs SPOMe) consistent with action at NK1 receptors. GR71251 (3 microM) did not antagonize responses to GR64349. 4. The NK2 antagonists L-659,877 and Ac-Leu-Asp-Gln-Trp-Phe-Gly-NH2 (R396) antagonized GR64349 although only R396 appeared to behave competitively (pKB 5.73). Neither L-659,877 (30 microM) nor R396 (30 microM) blocked responses to SPOMe. 5. For L-659,877 and R396, comparison was made between activity in guinea-pig trachea and in preparations known to contain tachykinin receptors predominantly of the NK2 type. In the rabbit trachea, both L-659,877 and R396 had effects similar to those in guinea-pig trachea. In contrast, in the rat colon muscularis mucosae, both L-659,877 and R396 appeared to behave competitively with pKB values against GR64349 of 7.83 and 6.90 respectively. 6. It is concluded that in guinea-pig trachea, contractile responses can be induced by activation of both NK1 and NK2 receptors. The present data are discussed with reference to the proposed existence of subtypes of the NK2 receptor.

Animals↗
PubMed1991

The BZLF1 protein of EBV has a coiled coil dimerisation domain without a heptad leucine repeat but with homology to the C/EBP leucine zipper.

The EBV transactivator protein BZLF1 can bind many sites in the EBV genome, most of which have homology to a consensus AP-1 site, the binding site for the fos/jun family of transcription factors. Here we present evidence that BZLF1 can also recognise the binding site for the CCAAT/enhancer binding protein C/EBP and that a BZLF1 binding site within the BZLF1 promoter is recognised by the C/EBP protein. Analysis of the BZLF1 DNA binding domain suggests that the BZLF1 protein binds to DNA as a dimer using sequences adjacent to a basic DNA binding motif. The BZLF1 dimerisation domain does not have a heptad repeat of leucine residues common to leucine zipper proteins but does have characteristics of a coiled coil structure, as judged by site directed mutagenesis. We therefore propose that the dimerisation domain of BZLF1 is structurally related to the coiled coil structure of leucine zippers but lacks the highly conserved leucine repeat. We show that the PZLF1 dimerisation domain has residues in common with the C/EBP leucine zipper and discuss the possible implications of this relationship.

Amino Acid Sequence↗
PubMed1991

In vitro DNA binding activity of Fos/Jun and BZLF1 but not C/EBP is affected by redox changes.

The leucine zipper family of proteins have a DNA binding domain composed of a leucine zipper dimerisation interface and a basic DNA binding structure. We show here that redox changes affect the in vitro DNA binding ability of a select subset of leucine zipper proteins. The bacterially expressed DNA binding domains of Fos/Jun and BZLF1 are unable to bind DNA under non-reducing conditions whereas binding of the C/EBP DNA binding domain is unaffected. Sensitivity to redox state is due to the presence of a conserved cysteine residue in the basic DNA binding motif of Fos, Jun and BZLF1 but not C/EBP. Under non-reducing conditions an intermolecular disulphide bridge is formed between the cysteine residues of each basic motif within a dimer, which prevents DNA binding. We show that oxidation of these C residues can be achieved enzymatically, using glutathione peroxidase, and that DNA binding protects them from oxidation. These data raise the possibility that intracellular changes in the redox state may differentially regulate the activity of leucine zipper family members. In addition the loss of DNA binding activity under non-reducing conditions has implications for the purification methods used to isolate proteins of the leucine zipper family for structural analysis.

Amino Acid Sequence↗
PubMed1990

p53 is associated with p34cdc2 in transformed cells.

The normal functioning of p53 is thought to involve p53 target proteins. We have previously identified a cellular 35 kd protein associated with p53 and now report evidence identifying this 35 kd protein as p34cdc2, product of the cell cycle control cdc2 gene. The association between p53 and p34cdc2 was detected in SV3T3 and T3T3 cell lines, both expressing the wild-type p53 phenotype, and in 3T3tx cells, expressing 'mutant' p53 phenotype. Binding of the mutant p53 phenotype with p34cdc2 was greatly reduced relative to wild-type. Complexes of p53-p34cdc2 may represent inactivation or activation of either component. The p34cdc2 kinase functions at cell cycle control points and is necessary for entry and passage through mitosis. It also operates in G1 and is involved in the commitment of cells into the proliferative cycle. Since we were unable to detect p53-p34cdc2 complexes in mitotic cells we propose that the interaction between p53 and p34cdc2 may be functional in cell growth control, possibly to promote or to suppress cell proliferation.

Animals↗
PubMed1990

Evidence for allosteric variants of wild-type p53, a tumour suppressor protein.

A tumour suppressor function for p53 is indicated in human lung cancer and in carcinoma of the colorectum. Loss of suppressor function, by mutation of the p53 gene, is associated with activation of p53 as an oncogene. The suppressor (wild type) and oncogenic (mutant) forms of the murine p53 protein are distinguishable at the molecular level by reactivity with anti-p53 monoclonal antibodies. For example, activated mutant p53 fails to react with PAb246 (p53-246 degrees). We now demonstrate that wild type p53 mRNA can be expressed either as p53-246+ or p53-246 degrees. We propose that p53-246 degrees may represent an allosteric variant of wild type p53 compatible with positive growth control. Thus, for wild type p53 the variants p53-246+ and p53-246 degrees may reflect suppressor and activator functions of p53 in the normal control of cell proliferation. For human p53 we present evidence that the epitope recognised by PAb1620 is analogous to that for PAb246 on murine p53. Thus the epitope for PAb1620 may prove to be of use as a marker for wild type human p53 with anti-oncogenic function.

Animals↗
PubMed1990

Morphological evaluation of atrioventricular septal defects by magnetic resonance imaging.

Twelve patients aged between 2 weeks and 22 months (median 6 weeks) with atrioventricular septal defects were examined with a 1.5 T, whole body, magnetic resonance imaging system. Ten patients had a common atrioventricular orifice (complete defect) while two patients had separate right and left valve orifices (partial defect). Associated cardiac malformations included the tetralogy of Fallot in two, isomerism of the right atrial appendages and pulmonary atresia in two, and right isomerism and double outlet right ventricle in one. All had previously been examined by cross sectional echocardiography. Eight subsequently had angiography and six underwent surgical correction. There was one operative death and three other deaths. Three of these patients underwent postmortem examinations. Small children and infants were scanned inside a 32 cm diameter head coil. Multiple electrocardiographically gated sections 5 mm thick, separated by 0.5 mm, were acquired using a spin echo sequence with echo time of 30 ms. A combination of standard and oblique imaging planes was used. Magnetic resonance imaging was more accurate than echocardiography in predicting the size of the ventricular component of the defect. It was also better than either echocardiography and angiography in identifying the presence of ventricular hypoplasia. All these findings were confirmed by surgical or postmortem examinations or both. Magnetic resonance imaging is capable of providing detailed morphological information in children with atrioventricular septal defects which is likely to be of value in their management.

Abnormalities, Multiple↗
PubMed1990

Incidence of fractures in a geographically defined population.

STUDY OBJECTIVE: The aim was to describe the population based age and sex specific incidence of fractures at different sites in a large English health district. DESIGN: Recording of fractures was accomplished by a specially constructed outpatient index and by record linkage to hospital inpatient information, for the three years surrounding the 1981 census. SETTING: The fracture index was held by the Department of Community Health in Leicester using data from the fracture clinic at the central large district general hospital, supplemented by hospital inpatient data from Trent Region and the two adjoining regions. PARTICIPANTS: The denominator population was the Leicestershire Health Authority resident population. In the three years, 12,711 fractures amongst males and 10,565 amongst females were recorded. MEASUREMENTS AND MAIN RESULTS: The overall estimated annual incidence of fractures was 100 per 10,000 population for males and 81 per 10,000 population for females. Below the age of 55 years all fractures showed a higher incidence amongst males but amongst the over 55s, there was a consistent fall in the male:female incidence ratio with some sites showing a striking female preponderance. The results also show an apparent age specific temporal increase in incidence at certain fracture sites compared with earlier British data, but fracture incidence figures still suggest lower rates in this country than in North America and some Scandinavian countries. CONCLUSIONS: These findings provide population based incidence data on a major public health problem and are consistent with the major determinants of osteoporosis and increase in falls in postmenopausal women. The temporal and geographical variation in fracture incidence remain to be explained.

Age Factors↗
PubMed1989

Controlled trial of haem arginate in acute hepatic porphyria.

A double-blind study comparing placebo and haem arginate was conducted in 12 patients with acute intermittent porphyria. 2 days after admission in attack patients were randomised to receive intravenous haem arginate 3 mg/kg per 24 h for 4 days or placebo. 9 patients were readmitted with a further attack and were given the alternative treatment. Before randomisation the paired attacks were of similar severity with respect to urinary porphobilinogen (PBG) excretion and clinical manifestations. With haem arginate the median PBG excretion of the 9 patients with two attacks (normal range 0-16 mumol per 24 h) fell significantly from 332 mumol per 24 h (range 137-722) on admission to a median lowest level of 40 (range 22-105). On placebo, median PBG excretion was 382 (range 196-542) on admission, falling to 235 (range 128-427). Median duration of admission after the start of treatment was 11 days (range 2-28) for placebo and 8 days (3-26) for haem arginate. Median total analgesic requirement between the start of treatment and discharge was 8150 mg pethidine equivalents (range 0-17,650) with placebo versus 6425 (range 50-20,650) with haem arginate. Phlebitis occurred in 5 patients on haem arginate and in 2 on placebo. Haem arginate effectively reduces porphyrin precursor overproduction in the acute porphyric attack but this reduction is not accompanied by striking resolution of the clinical manifestations of the attack.

Acute Disease↗
PubMed1989

p53 is associated with a 35 kD protein in cells transformed by simian virus 40.

The p53 protein is functionally implicated in the normal control of cell proliferation and, abnormally, in cell transformation. p53 is believed to function via specific cellular target proteins and activated mutants of p53 are associated with proteins of the hsp/hsc 70 heat shock family. However, cellular target proteins of wild type p53 have not, as yet, been described. With the aim of detecting such targets we have screened for cellular protein(s) that co-precipitate with wt p53. We now describe a 35 kD protein co-precipitated with p53 from SV40-transformed cells (a similar protein is detectable in non-viral transformed cells). The 35 kD protein does not appear to be a degradation product of p53. In sequential immunoprecipitations the 35 kD protein was depleted in parallel with p53, with which it appeared to be physically associated. This was substantiated by dissociation experiments in which the 35 kD protein was dissociated under conditions that also dissociate p53 from SV40 large T antigen. Thus wt p53 appears to interact with a cellular protein of 35 kD, the identity of which is under investigation.

Antigens, Polyomavirus Transforming↗
PubMed1989

A review of the practice of fibreoptic endoscopic dilatation of oesophageal stricture.

Over a 5-year period 82 patients underwent 244 fibreoptic endoscopic dilatations for oesophageal stricture. A total of 55 patients had benign peptic oesophageal stricture caused by reflux oesophagitis. Two-thirds of these patients had good symptomatic relief with dilatation combined with medical treatment of reflux, whereas one-third had an unsatisfactory result. The practice of endoscopic dilatation in benign stricture proved to be safe and was cost-effective as the procedure was carried out under intravenous sedation on a day-care basis. Three patients underwent dilatation for achalasia with good results in two cases. There were 16 patients with malignant oesophageal stricture and, in this group, fibreoptic endoscopic dilatation had little role to play in relieving dysphagia and its practice was associated with a substantial morbidity and mortality. Dilatation of malignant strictures facilitated biopsy and was used prior to oesophageal intubation. The virtues of the Atkinson or Celestin tube put in with the Nottingham introducer are summarised. Eight patients developed anastomotic stricture after resection of carcinoma of the oesophagus and dilatation provided only very transient relief of dysphagia in this group. Most anastomotic strictures represented recurrent malignancy and the difficulty in gaining biopsy proof endoscopically is emphasised. We advocate the early use of a CT scan in this situation to make the diagnosis of recurrent malignancy so that, if appropriate, palliative treatment can be instituted while the patient's general condition is good enough to benefit from it.

Adolescent↗
PubMed1989

Pathogenesis of venous ulceration in relation to the calf muscle pump function.

Air plethysmography has been used to quantitate venous reflux by measuring the average filling rate of the veins (venous filling index; in milliliters per second) on standing from the supine position, the ejection fraction of the calf muscle pump as a result of one tip-toe movement, and the residual volume fraction after 10 tip-toe movements. Thirty normal limbs, 110 limbs with primary varicose veins, 34 limbs with reflux in the deep veins but without occlusion, and 31 limbs with deep venous occlusion, with or without reflux, have been studied. An increase in the incidence of ulceration occurred with increasing values of reflux and decreasing values of the calf muscle pump ejection fraction. A poor ejection fraction was the primary cause of venous ulceration in limbs with minimal reflux. A good ejection fraction, however, significantly reduced the incidence of ulceration in limbs with marked reflux (p less than 0.05). The residual volume fraction, which expresses the combined effect of venous reflux and ejection fraction with rhythmic exercise, showed a good correlation with the incidence of ulceration and the measurements of ambulatory venous pressure (r = 0.81). The air-plethysmographic measurements completely assess the calf muscle pump function and provide an accurate method to identify the predominant hemodynamic factor (ejection fraction, reflux, or both) responsible for the clinical picture of the patient.

Adult↗
PubMed1988

Development of radioimmunoassays for free tetra-L-aspartyl-L-lysine trypsinogen activation peptides (TAP).

Tetra-L-aspartyl-L-lysine (D4K) containing trypsinogen activation peptides were synthesised on solid-phase supports. Synthetic D4K peptides were N-terminally haptenised and used to generate specific C-terminally directed anti-D4K antibodies. Affinity purification of antisera using Sepharose-immobilised synthetic D4K segregated two highly purified populations of anti-D4K antibodies, one eluting with EDTA recognising the calcium chelate and the other eluting with propionic acid recognising an alternative epitope on the anionic oligopeptide. Both specific anti-D4K antibodies were C-terminally directed and did not bind trypsinogen. Specific antisera and calcium-independent antibodies were used to develop and characterise solution and solid-phase immunoassays specific for free trypsinogen activation peptides (TAP assay), with a detection limit of 10(-11) M and between assay CV of 10.7% for the solution-phase system. The release of D4K peptides by enteropeptidase activation of trypsinogen and dog pancreatic secretion is demonstrated. TAP assays specifically indicate trypsinogen activation and may contribute to the recognition and understanding of disease states such as pancreatitis.

Amino Acid Sequence↗