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C Smyth

Publications and source records attributed to C Smyth.

At least 37 records · Page 2Linked to original sources
PubMed1997

Two-locus admixture linkage analysis of bipolar and unipolar affective disorder supports the presence of susceptibility loci on chromosomes 11p15 and 21q22.

Following a report of a linkage study that yielded evidence for a susceptibility locus for bipolar affective disorder on the long arm of chromosome 21, we studied 23 multiply affected pedigrees collected from Iceland and the UK, using the markers PFKL, D21S171, and D21S49. Counting only bipolar cases as affected, a two-point LOD of 1.28 was obtained using D21S171 (theta = 0.01, alpha = 0.35), with three Icelandic families producing LODs of 0.63, 0.62, and 1.74 (all at theta = 0.0). Affected sib pair analysis demonstrated increased allele sharing at D21S171 (P = 0.001) when unipolar cases were also considered affected. The same set of pedigrees had previously been typed for a tyrosine hydroxylase gene (TH) polymorphism at 11p15 and had shown some moderate evidence for linkage. When information from TH and the 21q markers was combined in a two-locus admixture analysis, an overall admixture LOD of 3.87 was obtained using the bipolar affection model. Thus the data are compatible with the hypothesis that a locus at or near TH influences susceptibility in some pedigrees, while a locus near D21S171 is active in others. Similar analyses in other datasets should be carried out to confirm or refute our tentative finding.

Bipolar Disorder↗
PubMed1997

Irritable bowel syndrome: the view from general practice.

OBJECTIVE: To determine the attributes of the irritable bowel syndrome (IBS) in general practice as perceived by the doctors. SUBJECTS AND METHODS: We administered a 93-item questionnaire about the terminology, diagnosis and treatment of the irritable bowel to 43 of 55 randomly selected general practitioners (28 men, 15 women). RESULTS: General practitioners were unfamiliar with the Manning criteria for the irritable bowel syndrome. Nevertheless, most of them diagnosed the irritable bowel with reasonable confidence and it is less troublesome to them than pelvic pain, headache or backache. Their main concern was excluding organic disease (63%) and 65% believed their patients shared this concern. Nevertheless, they ordered few tests and were often (72%) prepared to make the diagnosis on the initial visit. They estimated that they referred only 14% of IBS patients to specialists, in most cases (56%) because of an unsatisfied patient and in 35% because of an uncertain diagnosis. For treatment, most (77%) chose 'explanation and reassurance'. Virtually all employed drugs, usually several. CONCLUSION: General practitioners say they diagnose the irritable bowel syndrome with less difficulty than other common, painful disorders, but it would be helpful to find out exactly how they do so. Their confidence could be increased by use of diagnostic criteria. Patients referred to specialists are likely to be a minority of hard-to-satisfy people. The optimal approach to such patients should be developed by general practitioners and specialists together. Specialists should strive to satisfy the patient and confirm the diagnosis in the few that are referred. Drug usuage in the irritable bowel syndrome is more than is justified and should, in our view, be minimized.

Adult↗
PubMed1997

Test of Xq26.3-28 linkage in bipolar and unipolar affective disorder in families selected for absence of male to male transmission.

BACKGROUND: There have been several reports of linkage between genetic markers on the X chromosome at Xq26.3-28 and bipolar affective disorder in family samples obtained from distinct ethnic and geographical origins. As part of a genome search in a series of 23 UK and Icelandic families, specifically selected for their large size and power to resolve the issue of linkage heterogeneity, we have tested the hypothesis that there is a locus for a genetic subtype of bipolar affective disorder which is linked to this region. METHOD: In families selected on the basis of absent male to male transmission for affective disorder, we performed two-point and FASTMAP multipoint linkage analyses with markers spanning the region between the genetic loci DXS102 and F8. RESULTS: We found negative lod scores for several models of affection status in families selected under stringent and relaxed criteria for the absence of male to male transmission. CONCLUSIONS: In the family sample we have obtained, our study provides no support for the presence of a locus increasing genetic susceptibility to bipolar affective disorder in this region of the X chromosome. It is likely that our finding reflects heterogeneity of linkage for bipolar and genetically related unipolar disorder that exists in specific ethnic populations. Alternatively the X-linked subtype of the disorder may have been present only in a few of our small families resulting in loss of power to detect the Xq26.3-28 linked subtype.

Genetic Linkage↗
PubMed1996

Further tests for linkage of bipolar affective disorder to the tyrosine hydroxylase gene locus on chromosome 11p15 in a new series of multiplex British affective disorder pedigrees.

OBJECTIVE: This study was undertaken to confirm or refute previous reports that link bipolar affective disorder to polymorphic DNA markers at or near the gene for tyrosine hydroxylase. METHOD: A previous linkage analysis, which used a tetranucleotide repeat polymorphism at the tyrosine hydroxylase locus, of six Icelandic families was extended to include a new series of 17 multiply affected British families. RESULTS: Overall lod scores under the assumption of locus heterogeneity were between 1.20 and 1.40 at zero recombination with tyrosine hydroxylase, and these scores persisted across three affective disorder models. CONCLUSIONS: These results provide some support for linking affective disorder to this genetic region and suggest that additional linkage and association studies should be conducted to determine whether tyrosine hydroxylase or a nearby locus contributes to susceptibility to bipolar affective disorder in some families.

Alleles↗
PubMed1995

Pressure ulcer pain: assessment and quantification.

A cross-sectional study design was used to document perception of pressure ulcer pain in 132 patients in an acute care setting. Subjects were evaluated by means of the Folstein Mini-Mental State Examination, Beck's Depression Inventory, the Faces Pain Rating Scale, and the Visual Analog Scale for pain intensity. Charts were reviewed for demographic data and related medical treatments. The group comprised 44 subjects (33.3%) who were able to respond to the evaluation instruments and 88 subjects (66.7%) who were unable to respond to the evaluation tools. Forty-one percent of the respondents denied pressure ulcer pain and 59% reported pain of some type. According to the Faces Rating Scale, 32% of this group reported no pain and 68% reported some degree of pain. The respondents included 48% who scored below 24 on the Folstein Mini-Mental State Examination, indicative of cognitive impairment, and 52% who were found to be cognitively intact, with scores of 24 or above. Only 2% (n = 3) were given analgesics for pressure ulcer pain within 4 hours of the interview.

Adult↗
PubMed1994

A critical period for glutamate receptor-mediated induction of precocious puberty in female rats.

The excitatory amino acid glutamate and especially its NMDA subtype receptor are important components of the neural system that regulates sexual maturation. It is known that multiple daily injections of immature rats and monkeys with NMDA will induce precocious puberty. We have previously reported that a single daily injection of NMDA administered from 27 days of age to the day of vaginal opening (VO) is sufficient to synchronize and slightly accelerate (1-2 days) first ovulation in female rats. We have now optimized this treatment schedule and show that a higher dose of NMDA (20 mg/kg), or the racemic mixture N-methyl-D,L-aspartate (NMA; 30 mg/kg), initiated earlier in development (24 days to VO) significantly advances first ovulation (4 days). Rats induced to ovulate prematurely had normal estrous cycles. We also report that the same degree of precocity can be obtained when injections are discontinued well before first ovulation occurs. For example, NMA administered from day 21 to 25 or from day 24 to 28 accelerates sexual maturation to the same degree as if injections were continued until VO was observed. It is clear that the hypothalamic-pituitary-ovarian (H-P-O) axis is stimulated by daily NMDA treatment as shown by the dose-related luteinizing hormone (LH) release and by an estrogen-dependent rise in uterine weight. However, stimulation of the P-O axis with daily injections of GnRH (5 ng/100 g), which elicits an LH response slightly greater than NMDA (20 mg/kg), does not advance puberty. This suggests that NMDA induces some change in hypothalamic control which is not directly related to LH secretion. Interestingly, there also seems to be a critical period of NMDA effectiveness because daily injections of NMA (30 mg/kg) from day 16 to 20 do not induce precocious puberty. Since the ovaries respond with increased estrogen production (increased uterine weight) to gonadotrophin stimulation at this early age (16 days) we conclude that the hypothalamus may be relatively unresponsive to stimulation with NMDA. Paradoxically the hypothalamus is also hyporesponsive to NMDA in the period preceding spontaneous first ovulation. We now show that an LH dose-response curve for NMDA at age 28 days demonstrates that in NMDA-treated rats the LH response to NMDA is less than in the control group. Further, the hyporesponsiveness is not due to pituitary desensitization since an LH dose-response curve for GnRH at age 28 days is identical in the NMDA-treated and control groups.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1993

Odor-induced sexual maturation and expression of c-fos in the olfactory system of juvenile female mice.

Exposure to the urine or soiled bedding odors of novel adult males is known to accelerate puberty in juvenile female mice. To determine what part of the olfactory system is activated by these odors, the expression of c-fos in the main olfactory bulb (MOB) and the accessory olfactory bulb (AOB) of juvenile female mice was examined after their exposure to male-soiled bedding, peppermint odor or their own bedding. Fos-like immunoreactivity was found throughout the AOB of the juvenile female mice exposed to the bedding odors of adult males for 3 h. In contrast, dense staining was found in the granular cell layer of the MOB of mice exposed to peppermint odors for 3 h, whereas mice exposed to their own bedding failed to show immunostaining in the AOB and only slight or no staining in the MOB. These results indicate that social odors stimulate the expression of c-fos in the AOB while non-social odors activate the MOB. This method allows the identification of individual cells activated by the different odors and will be useful in locating other areas of the brain involved in the neuroendocrine changes underlying odor-induced precocious puberty.

Animals↗
PubMed1987

Estrogen and progesterone receptor assays in human breast cancer: sources of variation between laboratories.

The importance of cytosol preparation as a source of inter-laboratory variation in estrogen (ER) and progesterone (PR) receptor measurements was evaluated together with protein measurements and receptor assays for five laboratories in Sydney, Australia, using pooled, fragmented human breast cancer samples. Protein measurement was only a minor source of variation between the laboratories with a CV of 13%. For ER measurements, sources of variation due to either assay or cytosol preparation methods contributed 40 and 39% CV each. However, the variation due to assay method was reduced to 25% CV when the results from one laboratory with a known effect of a different ER assay protocol were excluded, suggesting that assay standardization could readily reduce this source of variation. In contrast, the source of a large cytosol error (39% CV) could not be identified. Variations in PR results were similar to ER, but the sources could not be accurately estimated. It is concluded that cytosol preparation as well as assay methods were major sources of between laboratory variation and need to be further investigated and standardized. This approach should reduce these sources of variation since it was found that the within laboratory cytosol and assay variations were only 13 and 18% CV, respectively, for the ER measurements.

Breast Neoplasms↗
PubMed1985

The effect of dopamine upon oxidative metabolism of brown fat adipocytes.

The effect of dopamine upon the oxygen consumption (QO2) of brown fat adipocytes was measured by polarography. The results showed a marked stimulation of QO2 by dopamine, similar to that induced by noradrenaline. The dopamine response could be blocked by haloperidol, butaclamol, propranolol and by high concentrations of tolazoline. These results suggest a role for dopamine in energy release from brown fat.

Adipose Tissue, Brown↗
PubMed1985

Diurnal variation in oxygen consumption of laboratory rats.

Oxygen consumption (VO2) was measured in Porton albino rats using a closed circuit apparatus. The groups studied were controls, cold-adapted animals, and those which had accumulated brown adipose tissue as a result of a cafeteria diet with a high energy content. It was possible to show in each group studied a difference in VO2 according to the time of day at which it was measured. This was consistent within each group studied. The diurnal variation shown (higher in the morning than in the afternoon) is characteristic of nocturnal animals. Measurement of VO2 then must be made within the same time-period or integrated over 24 h. Spurious correlations may otherwise occur.

Acclimatization↗
PubMed1985

The action of dopamine upon brown adipose tissue.

We increased the mass of interscapular brown adipose tissue in rats by dietary manipulation ("cafeteria" feeding), cold exposure, or by both. The animals were then used to determine the temperature response of the interscapular brown adipose tissue to dopamine or norepinephrine. These results, and the increase in blood glycerol values, were very similar for either catecholamine. These findings suggest that dopamine may have a role in releasing energy from brown adipose tissue similar to that of norepinephrine in the newborn infant.

Adipose Tissue, Brown↗
PubMed1984

Coli surface antigens 1 and 3 of colonization factor antigen II-positive enterotoxigenic Escherichia coli: morphology, purification, and immune responses in humans.

Enterotoxigenic Escherichia coli (ETEC) of serotype O6:H16, biotype A, bearing colonization factor antigen II (CFA/II) possesses two distinct coli surface antigens, CS1 and CS3, whereas CFA/II-positive ETEC of serotype O8:H9 manifests only CS3. CS1 has been shown to be fimbrial in nature, but heretofore the morphology of CS3 has not been described. Accordingly, by immune electron microscopy we investigated the morphological characteristics of CS3 on bacterial cells and after purification. CS3 was found to consist of thin (2-nm), flexible, wiry, "fibrillar" fimbriae, visible both on bacteria (O6:H16, biotype A, and O8:H9 strains) and in the pure state. In contrast, CS1 exists as wider (6-nm), rigid fimbriae on the surface of O6:H16, biotype A, strains. By the use of antisera to CS1 and CS3 in immune electron microscopy, immunodiffusion in gel, and immunoblotting techniques, CS1 and CS3 were found to be immunologically as well as morphologically distinct. Six of nine volunteers who developed diarrhea after challenge with an O139:H28 ETEC strain bearing CS1 and CS3 had significant serological rises to purified CS1 and CS3 antigens, suggesting that both antigens are elaborated in vivo, play a role in pathogenesis, and stimulate an immune response.

Antibody Formation↗