PubMed Health⌕ Search

Biomedical subjects

A Cook

Publications and source records attributed to A Cook.

At least 19 recordsLinked to original sources
PubMed1992

Signal shaping by voltage-gated currents in retinal ganglion cells.

The role of voltage-gated currents in information processing by retinal ganglion cells was assessed by comparing the light-evoked current and voltage responses of identified ganglion cells with those produced by current injection. These experiments show that the light-evoked signal is clipped at the bipolar-to-ganglion cell synapse because the synaptic current evoked by illumination with bright light is greater than that which the cell can convert into a change in action potential frequency. Ganglion cell responses to injected current fell into 2 classes: those producing sustained spiking responses and those producing transient responses. Further, this division is correlated with the light response of the cells; those producing transient responses to exogenous current produced transient responses to light, while those with sustained responses to current injection produced sustained responses to light flashes. The voltage-gated currents present in the ganglion cell membrane contribute to information processing in the retina by clipping the light-evoked signal and by producing transcience in the output of the retina.

Action Potentials↗
PubMed1992

Eight years' experience of clinical activity in an outpatient fracture clinic.

Major changes to the method of planning and provision of health care in Britain have led to the introduction of contracts as the main means through which services are procured. Never before has the need for accurate and comprehensive clinical information been greater. Yet comprehensive outpatient information, though planned, is not yet available, and there is relatively little experience of such systems which have been introduced in individual localities. Fracture clinic patients are an important group of outpatient, not least because interventions are often undertaken as an integral part of the outpatient episode. This is relevant for estimating resource use and for pricing, but until now has been 'hidden' work as far as conventional information systems are concerned. This study describes the establishment and manifestation of a clinical information system based on a fracture clinic serving the majority of a population of 850,000. Information was gathered over 8 years on 61,635 patients, who had 72,984 diagnoses and received 93,878 treatments. An information system of the type described in this study can be of great value as part of the contracting process (for both purchasers and providers of orthopaedic services), as a basis for clinical audit and research, and to facilitate undergraduate and postgraduate teaching.

Adolescent↗
PubMed1992

Disposition of the atrioventricular conduction tissues in the heart with isomerism of the atrial appendages: its relation to congenital complete heart block.

OBJECTIVES: Our goal was to compare histologically the mechanisms producing congenital complete heart block in normally structured hearts and in hearts with isomerism of the atrial appendages. BACKGROUND: It is known that several different histologic patterns can underscore the existence of congenital complete heart block in the normally structured heart, and that block is particularly frequent in the setting of isomerism of the atrial appendages. The histologic findings in the latter setting were compared and contrasted with those found in the normally structured heart. METHODS: Serial section techniques were used to study 14 hearts with isomerism of the atrial appendage (12 with left isomerism and 2 with right isomerism) and 7 normally structured hearts. RESULTS: Discontinuity between the atrioventricular (AV) node and the ventricular conduction tissues was found in 10 of the 12 hearts with left isomerism; the other 2 hearts had a normally formed conduction axis and heart block was not present in these cases. In both hearts with right isomerism, "slings" of ventricular conduction tissue connected dual AV nodes; congenital complete heart block was not present in either case. In six of the seven cases with a normally structured heart, anti-Ro antibodies had been found in the maternal serum. All six of these hearts had discontinuity between the atrial tissues and the ventricular conduction axis. Intraventricular discontinuity was found in the seventh case, in which anti-Ro antibodies were not found in the mother. CONCLUSIONS: The pattern of congenital complete heart block in cases with left isomerism is discontinuity between the AV node and the conduction axis, in contrast to the pattern of atrial-axis discontinuity produced in the normally structured heart when anti-Ro antibodies are found in the maternal serum.

Abnormalities, Multiple↗
PubMed1992

Conserved motifs in Fos and Jun define a new class of activation domain.

Fos and Jun form a tight heterodimeric complex that activates transcription by AP1 sites. We have recognized that two adjacent regions of the Jun A1 activation domain are conserved in the Fos protein, and we refer to these two homologous regions as homology box 1 (HOB1) and homology box 2 (HOB2). Using GAL4 chimeras, we show that the HOB1/HOB2 region of Fos and Jun is an independent activation domain in which HOB1 and HOB2 act cooperatively to activate transcription. This cooperativity is retained after the replacement of Fos HOB1 or HOB2 with the equivalent domain of Jun or when duplicated HOB1/HOB1 and HOB2/HOB2 combinations are generated. In the Fos protein, HOB1 or HOB2 can also cooperate with a distinct domain at the carboxyl terminus of the protein. Using the HOB2 consensus sequence as a guide, we identified a HOB2-containing activation domain in the CCAAT/enhancer binding protein (C/EBP) protein. This HOB2 motif can cooperate with as yet undefined sequences in C/EBP and will function even when linked to Jun HOB1. Thus, HOB1 and HOB2 represent inert "cooperating modules" that are combined to generate a functional activation domain. Each of these modules has the potential to cooperate with both distinct and identical domains. The presence of HOB-like modules in three different transcription factors indicates that the HOB motifs characterize a new class of activation domain. These motifs can be used now to identify other transcription factors with such modular characteristics.

Amino Acid Sequence↗
PubMed1992

Accuracy of a portable interpretive ECG machine in diagnosis of acute evolving myocardial infarction.

From a study of 526 patients having automatic ECG analysis, criteria were established which diagnosed acute evolving Q wave myocardial infarction with 71% sensitivity and 98% specificity. Specificity was 100% when patients with known previous Q wave infarction were excluded. In pre-hospital practice the high sensitivity and specificity were maintained. This method appears appropriate, when other criteria are met, for paramedic-initiated pre-hospital thrombolysis with remote supervision of a cardiologist by telephone.

Adult↗
PubMed1992

Closely linked H2B genes in the marine copepod, Tigriopus californicus indicate a recent gene duplication or gene conversion event.

Two nonallelic histone gene clusters were characterized in the marine copepod, Tigriopus californicus. The DNA sequence of one of the clusters reveals six genes in the contiguous arrangement of H2B, H1, H3, H4, H2B and H2A. The order of genes within the second cluster is H3, H4, H2B and H2A. There is no evidence for the presence of an H1 gene in this cluster. Comparison of the three copepod H2B genes reveals a high degree of similarity between the 5' upstream regions and between the amino terminal halves of the two H2B genes found within the same cluster. From these data we infer that gene duplication and/or gene conversion events occurred within this cluster in the recent past.

Alleles↗
PubMed1992

Immunocytochemical and electrophysiological investigations of central neurones in the parasitic nematode Ascaris suum.

Here we report on preliminary investigations into the morphological, neurochemical and electrophysiological characteristics of central neurones in the parasitic nematode Ascaris suum. The neurones do not display all or none action potentials and apparently have low resting membrane potentials. Neurones have been shown to respond to acetylcholine. Immunoreactivity to a diverse range of neuropeptides has been demonstrated.

Acetylcholine↗
PubMed1991

Hypoplastic left heart syndrome: effects of fetal echocardiography on birth prevalence.

Hypoplastic left heart syndrome was diagnosed prenatally and confirmed in 105 fetuses since 1983 at a regional referral centre. An increased detection rate since 1988 is probably related to increased experience in the use of a four-chamber view of the fetal heart during routine obstetric ultrasound scanning. When the diagnosis was made sufficiently early, most parents chose to terminate the pregnancy after the prognosis and surgical options were explained. By contrast, after an increase in the mid 1980s, since 1988 there has been a striking fall in the number of newborn babies with hypoplastic left heart syndrome treated at a supraregional referral centre. More widespread use of four-chamber cardiac screening during routine fetal ultrasonography may reduce the number of newborn babies with hypoplastic left heart syndrome--a factor which should be taken into account when the likely requirements for neonatal cardiac transplantation facilities are calculated.

Abortion, Induced↗
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↗