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Biomedical subjects

C T Jones

Publications and source records attributed to C T Jones.

At least 19 recordsLinked to original sources
PubMed2000

Cardiac catheterization reduces resource utilization in patients with chronic chest pain.

The evaluation of patients with recurrent chest pain accounts for a significant proportion of the $274 billion annual cost of cardiovascular services in the United States. Our investigation examines the impact of coronary angiography on subsequent use of medical resources for evaluation of chest pain symptoms. The study seeks to determine whether a finding of noncritical coronary artery disease on cardiac catheterization leads to a reduced use of resources for subsequent evaluation and treatment of chest pain syndromes. Our study included 22 consecutive patients who had sought evaluation for chest pain symptoms, and who had persistence of symptoms after functional testing. Cardiac catheterization demonstrated angiographically mild coronary artery disease (stenosis less than 50%) in these patients. The patient cohort accounted for 22 emergency room evaluations and 41 ambulatory clinic evaluations in the 2.5 years before cardiac catheterization. In the 2.5-year period after catheterization, these patients had only 3 emergency room visits and 1 ambulatory clinic visit for chest pain evaluation (P < 0.001). There was a significant reduction in the number of prescriptions written for topical and oral nitrates (32% precatheterization vs. 5% postcatheterization, P < 0.04), but not of beta-blockers (26% vs. 21%, P = 0.53) or calcium blockers (32% vs. 32%, P = 1.0). Furthermore, most of the 21 surviving patients were found subsequently to have a noncardiac basis for their pain: pericarditis was felt to be the cause of chest pain in 4 patients, pulmonary disease in 7 patients, and gastrointestinal conditions in 8 patients. Diagnostic coronary arteriography may identify a subset of patients in whom a finding of noncritical coronary artery disease leads to a reduction in physician visits for evaluation of chest pain syndromes and reduced use of nitrates. In addition, when coronary artery disease is known to be mild, a noncardiac etiology for the chest pain can be sought. These results may decrease the use of expensive medical resources and encourage full occupational and lifestyle rehabilitation.

Angina Pectoris↗
PubMed2000

Differences in gene density on chicken macrochromosomes and microchromosomes.

The chicken karyotype comprises six pairs of large macrochromosomes and 33 pairs of smaller microchromosomes. Cytogenetic evidence suggests that microchromosomes may be more gene-dense than macrochromosomes. In this paper, we compare the gene densities on macrochromosomes and microchromosomes based on sequence sampling of cloned genomic DNA, and from the distribution of genes mapped by genetic linkage and physical mapping. From these different approaches we estimate that microchromosomes are twice as gene-dense as macrochromosomes and show that sequence sampling is an effective means of gene discovery in the chicken. Using this method we have also detected a conserved linkage between the genes for serotonin 1D receptor (HTR1D) and the platelet-activating factor receptor protein gene (PTAFR) on chicken chromosome 5 and human chromosome 1p34.3. Taken together with its advantages as an experimental animal, and public access to genetic and physical mapping resources, the chicken is a useful model genome for studies on the structure, function and evolution of the vertebrate genome.

Animals↗
PubMed1999

The dynamics of chromosome evolution in birds and mammals.

Comparative mapping, which compares the location of homologous genes in different species, is a powerful tool for studying genome evolution. Comparative maps suggest that rates of chromosomal change in mammals can vary from one to ten rearrangements per million years. On the basis of these rates we would expect 84 to 600 conserved segments in a chicken comparison with human or mouse. Here we build comparative maps between these species and estimate that numbers of conserved segments are in the lower part of this range. We conclude that the organization of the human genome is closer to that of the chicken than the mouse and by adding comparative mapping results from a range of vertebrates, we identify three possible phases of chromosome evolution. The relative stability of genomes such as those of the chicken and human will enable the reconstruction of maps of ancestral vertebrates.

Animals↗
PubMed1997

Gene homologs on human chromosome 15q21-q26 and a chicken microchromosome identify a new conserved segment.

The genes for insulin-like growth factor 1 receptor (IGF1R), aggrecan (AGC1), beta2-microglobulin (B2M), and an H6-related gene have been mapped to a single chicken microchromosome by genetic linkage analysis. In addition, a second H6-related gene was mapped to chicken macrochromosome 3. The Igf1r and Agc1 loci are syntenic on mouse Chr 7, together with Hmx3, an H6-like locus. This suggests that the H6-related locus, which maps to the chicken microchromosome in this study, is the homolog of mouse Hmx3. The IGF1R, AGC1, and B2M loci are located on human Chr 15, probably in the same order as found for this chicken microchromosome. This conserved segment, however, is not entirely conserved in the mouse and is split between Chr 7 (Igf1r-Agc) and 2 (B2m). This comparison also predicts that the HMX3 locus may map to the short arm of human Chr 15. The conserved segment defined by the IGF1R-AGC1-HMX3-B2M loci is approximately 21-35 Mb in length and probably covers the entire chicken microchromosome. These results suggest that a segment of human Chr 15 has been conserved as a chicken microchromosome. The significance of this result is discussed with reference to the evolution of the avian and mammalian genomes.

Aggrecans↗
PubMed1995

Superoxide dismutase mutations in an unselected cohort of Scottish amyotrophic lateral sclerosis patients.

Mutations in the Cu/Zn superoxide dismutase (SOD1) gene are responsible for some cases of familial amyotrophic lateral sclerosis (ALS). We have shown that SOD1 mutations can also occur in apparently sporadic ALS. To establish how often this happens we have undertaken a study of the prevalence of SOD1 mutations in an unselected cohort of Scottish ALS patients, with both sporadic (n = 57) and familial (n = 10) disease. Single strand conformation polymorphism analysis was used to scan for new mutations, and selective restriction enzyme digestion to screen for 11 of the 20 SOD1 mutations published to date. We detected mutations in five (50%) of the familial ALS patients and also in four (7%) of the sporadic patients. One mutation, ile113thr, seems to be particularly prevalent in the Scottish population since it was detected in a total of 6/67 (9%) unrelated cases.

Aged↗
PubMed1994

Muscarinic involvement in vascular and adrenal medullary responses to splanchnic nerve stimulation in conscious calves.

Stimulation of the peripheral end of the right splanchnic nerve (4 Hz for 10 min) in the presence of hexamethonium caused a small but significant rise in mean aortic blood pressure which was subsequently abolished by atropine. There were also small but significant increases in the outputs of catecholamines, [Met5]-enkephalins and corticotrophin releasing factor (CRF) from the right adrenal gland. The catecholamine response was roughly halved after atropine while the outputs of enkephalins and CRF were unaffected. It is concluded that splanchnic sympathetic postganglionic neurones supplying the vasculature are completely blocked by cholinergic blockade whereas adrenal medullary responses persist in an attenuated form.

Adrenal Medulla↗
PubMed1994

Identification of a novel exon 4 SOD1 mutation in a sporadic amyotrophic lateral sclerosis patient.

We have been screening a cohort of 46 sporadic and 10 familial amyotrophic lateral sclerosis patients for mutations in the superoxide dismutase gene (SOD1) using a combination of SSCP and direct PCR sequencing. A novel missense mutation (Asp101Asn) has been detected in one sporadic patient and a previously reported mutation has been found in two familial cases.

Amyotrophic Lateral Sclerosis↗
PubMed1994

Identification of GPCMV infected cells in vitro and in vivo with a monoclonal antibody.

A monoclonal antibody was made which identifies a 160-180 kDa structural protein in guinea pig cytomegalovirus (GPCMV) infected cells by Western blot using non-reducing conditions. This protein was shown to be a virion structural protein by purification of GPCMV on a density viscosity gradient and Western blot analysis. Phosphoanacetic acid (PAA) experiments suggest that the protein is a late GPCMV protein. In vitro the monoclonal antibody labels a cytoplasmic protein in infected guinea pig embryo fibroblasts by 12 h postinfection. The monoclonal antibody also identifies GPCMV infected cells in vivo in paraffin embedded formalin fixed tissue.

Animals↗
PubMed1994

Adrenal responses to the peptide PACAP in conscious functionally hypophysectomized calves.

Intra-aortic infusions of pituitary adenylate cyclase-activating peptide-(1-38) (PACAP) produced a dose-related fall in aortic blood pressure over the range of 4-40 pmol.min-1.kg-1 in the presence of exogenous adrenocorticotropic hormone-(1-24) (ACTH, 2 ng.min-1.kg-1 i.v.; P < 0.01). At the higher dose there was a significant fall in adrenal vascular resistance in the absence, but not in the presence, of ACTH. PACAP also produced a dose-related increase in right adrenal cortisol output over the same range, which was significantly greater in the absence of exogenous ACTH (P < 0.01). At the higher dose, PACAP produced small but significant increases in adrenal epinephrine and norepinephrine output (P < 0.01) both in the presence and the absence of ACTH. There was also a small rise in Met5-enkephalin output, and corticotrophin-releasing factor (CRF) was released in the presence, but not in the absence, of ACTH. It is concluded that PACAP is capable of exerting potent steroidogenic and vasodilator effects in the adrenal gland in the normal conscious calf and of releasing significant amounts of catecholamines, enkephalins, and CRF from the adrenal medulla. These findings identify PACAP as a candidate neuromodulator in the adrenal gland in this species.

Adrenal Cortex↗
PubMed1994

Effects of substance P on adrenal responses to acetylcholine in conscious calves.

The effect of intra-aortic infusions of substance P (SP; 10 or 20 pmol.min-1.kg-1) on adrenal responses to acetylcholine (4.5 nmol.min-1.kg-1 ia) have been investigated in functionally hypophysectomized calves given exogenous adrenocorticotropic hormone (0.7 pmol.min-1.kg-1). At the lower dose, SP had no effect on cortisol output. In contrast, SP inhibited the output of both catecholamines and enkephalins in response to acetylcholine, without affecting the output of corticotropin-releasing factor (CRF). Increasing the dose of SP to 20 pmol.min-1.kg-1 ia significantly reduced the outputs of both cortisol and CRF (P < 0.025 and 0.01 respectively). It is concluded that SP is capable of modulating both adrenal cortical and medullary responses to acetylcholine and that the latter are more sensitive to this influence than the former.

Acetylcholine↗
PubMed1993

Screening Alzheimer's disease patients for mutations in the amyloid precursor protein gene.

Over the past two years a series of different mutations has been discovered in the amyloid precursor protein (APP) gene in patients with Alzheimer's disease. All have been clustered in exons 16 and 17, a region encoding the beta A4 peptide found in the amyloid deposits of neuritic plaques and cerebral blood vessels. We have used the powerful technique of denaturing gradient gel electrophoresis to screen for mutations in exons 7, 16 and 17 of the APP gene in a cohort of 105 patients with presenile dementia of the Alzheimer type and 71 patients with autopsy-confirmed senile Alzheimer's disease. No new mutations were found, confirming earlier suggestions that APP mutations account for only a small proportion of cases of familial and sporadic Alzheimer's disease.

Adult↗
PubMed1993

Adrenal cortical and medullary responses to acetylcholine and vasoactive intestinal peptide in conscious calves.

1. Adrenal responses to intra-aortic infusions of acetylcholine and vasoactive intestinal peptide (VIP) have been investigated in functionally hypophysectomized calves given exogenous adrenocorticotrophic hormone (ACTH, 2 ng min-1 kg-1 I.V.). 2. Infusions of VIP at a dose of 0.13 micrograms min-1 kg-1 caused a small, but significant increase in adrenaline and noradrenaline output which was, however, far below the level recorded previously in response to acetylcholine (0.7 micrograms min-1 kg-1). In contrast, these doses of the two agonists produced closely similar rises in adrenal cortisol output. 3. The steroidogenic effects of acetylcholine and VIP were found to be strictly additive and no evidence of potentiation was obtained in relation to either cortical or medullary responses or in the case of any of the cardiovascular responses which were monitored. 4. Intra-aortic infusions of VIP, at a dose which produced a substantial increase in adrenal steroidogenesis (0.065 micrograms min-1 kg-1), had no effect on the output of catecholamines, enkephalin-like immunoreactivity or corticotrophin-releasing factor, either in the presence or absence of acetylcholine. 5. It is concluded that VIP is unlikely to modulate adrenal medullary responses to muscarinic stimulation in this species as it has been claimed to do in the rat and does not potentiate adrenal steroidogenesis in response to acetylcholine as it does to ACTH.

Acetylcholine↗
PubMed1993

Changes in uterine G-protein content during pregnancy in the guinea pig.

G-protein content (G(i) alpha, Gs alpha, Gq/11 alpha G(o) alpha and beta subunits) has been measured in membranes prepared from guinea pig uterus at different stages of pregnancy using SDS-PAGE and immunoblotting. Quantification using HRP- or 125I-labelled IgG as second antibody showed a good correlation between added membrane protein and measured G-protein content. Gs alpha appears as two bands of 45 kDa and 52 kDa respectively, the content of both were comparatively high in the non-pregnant uterus and fell about 4-fold close to term (60-67 days). G(i) alpha showed the converse with low level in membranes from the non-pregnant uterus with level approximately 6-fold higher by term. G(o) alpha exhibited changes similar to G(i) alpha. The changes in the content of Gq/11 alpha where biphasic, with comparatively high levels in membranes from the non-pregnant uterus, a sharp fall early in pregnancy followed by a 3-fold rise by near term. The uterine membrane content of the common beta subunit exhibited changes comparable to that of G(i) alpha and G(o) alpha with a 6-fold rise in content between non- and late-pregnant. Measurement of the effect of GTP gamma S action on phosphatidylinositol phospholipase C activity in uterine membranes with exogenous substrate showed pregnancy-dependent effects. In membranes from the non-pregnant uterus 0.1 microM GTP gamma S caused a modest stimulation of activity of 16 +/- 1.9%, whilst at 100 microM it inhibited the enzyme by 25 +/- 6.48%. In membranes from the late-pregnant guinea pig uterus GTP gamma S at both concentrations caused stimulation of enzyme activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Autonomic control of adrenal function.

Recent studies of adrenal function in conscious calves are reviewed. These have involved collecting the whole of the adrenal effluent blood from the right adrenal gland at intervals and, where necessary, prior functional hypophysectomy by destruction of the pituitary stalk under general halothane anaesthesia 3 d previously. The adrenal medulla was found to release numerous neuropeptides, in addition to catecholamines, in response to stimulation of the peripheral end of the right splanchnic nerve, which was carried out below behavioural threshold. Many of these responses were enhanced by stimulating intermittently at a relatively high frequency. Intra-aortic infusions of a relatively low dose of acetylcholine (4.5 nmol min-1 kg-1) elicited similar responses. In the adrenal cortex, agonists which either potentiated the steroidogenic response to ACTH or exerted a direct steroidogenic action included VIP, CGRP, CRF and ACh acting via muscarinic receptors. Stimulation of the peripheral end of the right splanchnic nerve strongly potentiated the steroidogenic response to ACTH and there is compelling evidence that the innervation normally plays an important part in cortisol secretion.

Acetylcholine↗