PubMed Health⌕ Search

Biomedical subjects

A Cook

Publications and source records attributed to A Cook.

At least 109 records · Page 6Linked to original sources

Toxin production, adherence and protein expression by clinical Aeromonas spp. isolates in broth and human pooled ileostomy fluid.

The physiological behaviour of clinical Aeromonas spp. isolates was compared following culture in a conventional broth and human pooled ileostomy fluid (PIF). Protein expression was markedly affected by the growth medium, with an overall reduction in whole cell proteins in bacteria grown in ileostomy fluid. In addition, novel outer membrane proteins were produced in PIF but not in broth. The majority of A. hydrophila and A. sobria isolates produced toxin in both broth and PIF, whereas no cytotoxin positive A. caviae were found. Toxin titres were at least two doubling dilutions higher in 40% and 21% of A. hydrophila and A. sobria isolates, respectively, following culture in brain heart infusion broth compared with PIF. Bacterial adherence to Vero and A-549 cells was significantly more common in A. hydrophila (53%) and A. sobria (64%) than in A. caviae (15%) (P < 0.01). We observed increased adherence by 6 aeromonas strains previously classified as adherence-positive, but not by 6 non-adherers, in PIF compared with brain heart infusion broth. The influence of growth medium on the expression of potential virulence determinants by Aeromonas spp. provides a rationale for the use of human ileostomy fluid in future in vitro studies, in order to simulate the nutrient conditions found in vivo.

Aeromonas↗

Effect of pattern glare and colored overlays on a stimulated-reading task in dyslexics and normal readers.

Scotopic sensitivity syndrome or the Irlen syndrome describes symptoms of asthenopia anamolous visual performance experienced while reading that are lessened by colored filters. One putative explantation for this condition relates to pattern glare: a hypersensitivity to repetitive patterns, including lines of print on a page. Experiment 1 used a placebo-controlled paradigm to investigate the effect of pattern glare and colored overlays on performance at a simulated reading visual search task. Despite the fact that the subjects were university students, the results showed a tendency, of border-line significance, to support the conclusion that colored filters seem to improve reading through ameliorating pattern glare. In experiment 2 we compared the prevalence of pattern glare in matched groups of dyslexic children and good readers. The dyslexic group reported more pattern glare, but also reported more glare from a control stimulus. Pattern glare in the dyslexic group was directly correlated with flicker sensitivity. The results are related to recent research on visual processing and ocular-motor function in dyslexia.

Adult↗

c-Fos-induced activation of a TATA-box-containing promoter involves direct contact with TATA-box-binding protein.

Transcriptional activation in eukaryotes involves protein-protein interactions between regulatory transcription factors and components of the basal transcription machinery. Here we show that c-Fos, but not a related protein, Fra-1, can bind the TATA-box-binding protein (TBP) both in vitro and in vivo and that c-Fos can also interact with the transcription factor IID complex. High-affinity binding to TBP requires c-Fos activation modules which cooperate to activate transcription. One of these activation modules contains a TBP-binding motif (TBM) which was identified through its homology to TBP-binding viral activators. This motif is required for transcriptional activation, as well as TBP binding. Domain swap experiments indicate that a domain containing the TBM can confer TBP binding on Fra-1 both in vitro and in vivo. In vivo activation experiments indicate that a GAL4-Fos fusion can activate a promoter bearing a GAL4 site linked to a TATA box but that this activity does not occur at high concentrations of GAL4-Fos. This inhibition (squelching) of c-Fos activity is relieved by the presence of excess TBP, indicating that TBP is a direct functional target of c-Fos. Removing the TBM from c-Fos severely abrogates activation of a promoter containing a TATA box but does not affect activation of a promoter driven only by an initiator element. Collectively, these results suggest that c-Fos is able to activate via two distinct mechanisms, only one of which requires contact with TBP. Since TBP binding is not exhibited by Fra-1, TBP-mediated activation may be one characteristic that discriminates the function of Fos-related proteins.

Adenovirus E1A Proteins↗

The effect of cancer diagnosis and treatment on hand function.

Cancer diagnosis and treatment can have a profound effect upon hand function, presenting a challenge to the occupational therapist. The therapist who specializes in oncology or hand therapy must have knowledge of the medical treatment model in regard to cancer conditions and must be able to set realistic goals that consider the patient's medical prognosis as well as the effect the disease or medical treatment has on the patient's physical and emotional functioning. The challenge to therapists in this area of practice will be to conduct research to verify or validate the effectiveness of the occupational therapy interventions currently provided. As cancer is diagnosed at earlier stages of the disease and survival improves after cancer treatment, hand therapy may improve the functional outcomes of persons with cancer. This judgment of rehabilitation oncology practice will need to be confirmed by research.

Antineoplastic Agents↗

Antibodies to type II collagen in human serum: storage effects and role of IgM antiidiotype in regulation.

OBJECTIVE: To investigate the observation that IgG reactivity to human denatured type II collagen (denatured CII) is increased in normal human serum stored at 4 degrees C compared to serum stored at -20 degrees C. METHODS: Reactivity was measured by ELISA, and the effect of heating was also assessed. Serum was separated on affinity columns and mixing experiments were performed with the resultant fractions to test for inhibitory or enhancing effects. RESULTS: There is a storage labile and heat labile inhibitor in the IgG depleted fraction of serum stored at -20 degrees C from healthy subjects, and an inhibitor is present in some pooled human IgM preparations which reduces the reactivity of antibody to human CII in serum from both healthy subjects and patients with rheumatoid arthritis. CONCLUSIONS: Storage conditions and heat significantly affect IgG antibodies to denatured CII but not antibodies to other antigens. These effects may be mediated by the presence of an IgM antiidiotype against the IgG antibody to denatured CII.

Antibodies, Anti-Idiotypic↗

The retinoblastoma protein binds E2F residues required for activation in vivo and TBP binding in vitro.

The retinoblastoma (RB) tumour suppressor protein is capable of repressing the activity of promoters containing DNA binding sites for the transcription factor E2F. Recently a protein which binds RB and possesses the DNA binding characteristics of E2F has been cloned. Here we show that the E2F activation domain is the target for RB-induced repression. RB can silence the 57 residue E2F activation domain but cannot effectively repress an E2F mutant which has reduced RB binding capacity. Extensive mutagenesis of E2F shows residues involved in RB binding are required for transcription activation. Mutations which affect both functions most dramatically lie within the minimal RB binding region. A further subset of sensitive residues lies within a new repeat motif E/DF XX L X P which flanks the minimum RB binding site. These data show that RB can mask E2F residues involved in the activation process, possibly by mimicking a component of the transcriptional machinery. Consistent with this model, we find that the TATA box binding protein TBP can bind to the E2F activation domain in vitro in a manner indistinguishable from that of RB.

Amino Acid Sequence↗

The activation domain of transcription factor PU.1 binds the retinoblastoma (RB) protein and the transcription factor TFIID in vitro: RB shows sequence similarity to TFIID and TFIIB.

The retinoblastoma (RB) tumor suppressor protein and the TATA-box-binding protein TFIID form contacts with a number of viral transactivator proteins. One of these, the adenovirus E1A protein, can bind to both proteins. Here we present evidence that the cellular transcription factor PU.1 can bind to both RB and TFIID. Like E1A, PU.1 binds to the conserved C-terminal domain of TFIID and to the RB "pocket" domain. The PU.1 sequences required to bind either protein lie within a 75-amino acid region which functions as an independent activation domain in vivo. The ability of PU.1 to contact directly both RB and TFIID through the same 75-residue domain prompted us to look for sequence similarity between these two proteins. We find that the previously defined domain A of the RB pocket shows sequence similarity to the conserved C terminus of TFIID, whereas domain B shows sequence similarity to a second general transcription factor, TFIIB. The potential for RB to influence transcription by using TFIID- and TFIIB-related functions is discussed.

Amino Acid Sequence↗

Genetic heterogeneity in families with hereditary multiple exostoses.

We have carried out a linkage analysis on 11 families segregating gene(s) for hereditary multiple exostoses (EXT). Four highly informative, short tandem-repeat (STR) markers that have been physically mapped to an interval surrounding the Langer-Giedion chromosomal region (8q24.11-q24.13) were used in a multipoint linkage analysis. Significant evidence for linkage of EXT with genetic heterogeneity was found. A model of heterogeneity with linkage of the disease gene to the STR markers in 70% of the families (with a 95% confidence interval of 26%-96%) produced a maximum LOD score of 8.11, with the most likely position of EXT between D8S85 and D8S199. Thus there are at least two genes that are capable of causing hereditary multiple exostoses, one in the Langer-Giedion region and one at another, unlinked location.

Cell Line↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗