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Biomedical subjects

C A Graham

Publications and source records attributed to C A Graham.

At least 109 records · Page 6Linked to original sources

A prospective treatment study of premenstrual symptoms using a triphasic oral contraceptive.

Eighty-two women with complaints of moderate to severe premenstrual symptoms were recruited for a double-blind, controlled trial of a triphasic oral contraceptive (o.c.). Subjects made daily ratings of symptoms for at least one baseline cycle and were then randomly assigned to receive either placebo or o.c. for three months. Twenty-three women dropped out of the study (18 o.c., 5 placebo), 13 failed to show prospective confirmation of moderate to severe premenstrual symptoms, and one placebo subject had an anovulatory cycle. Forty-five women with prospectively-confirmed premenstrual changes (20 o.c., 25 placebo) completed the study. Premenstrual breast pain and bloating were significantly reduced with active treatment compared to placebo (p less than 0.03) but there were no beneficial effects of the o.c. over placebo for any of the mood symptoms. Women who received o.c.s reported decreased sexual interest after starting treatment and this effect was independent of any adverse influence on mood.

Adult↗

Prenatal exclusion of Norrie's disease.

We report on the use of DNA marker probes and linkage analysis to exclude Norrie's disease in the male fetus of a high risk carrier. There are no clinical markers in females carrying the Norrie's disease gene; thus DNA linkage analysis is an essential technique in the management of families 'at-risk' for this severe ophthalmic disease. The principles of DNA linkage are discussed.

Blindness↗

X-linked clinical anophthalmos. Localization of the gene to Xq27-Xq28.

A Northern Ireland family is reported on, in which there is X-linked inheritance of clinical anophthalmos. Multi-point linkage analysis suggests that the gene is localized to the Xq27-28 region (Z = 1.9, Theta = 0.08), though not between the DNA markers DX13 and Factor VIII.

Anophthalmos↗

DNA analysis and recombination in X-linked retinitis pigmentosa.

X-linked retinitis pigmentosa is a hereditary retinal degenerative disorder which has been localised to the proximal short arm of the X chromosome. Recent evidence suggests that the disorder is heterogeneous with two possible loci for the disease mutation. DNA analysis on the family presented in this paper showed that the mutation mapped to the more telomeric locus (RP3), thus enabling two flanking polymorphic DNA probes (XJ1.1 and M27 beta) to be used for the detection of female carriers in the family. In none of the carriers was a tapetal reflex (metallic sheen) observed.

Adult↗

A T cell receptor beta chain polymorphism is associated with patients developing insulin-dependent diabetes after the age of 20 years.

We have studied the BglII polymorphism near the T cell receptor beta chain constant region (TcR-C beta) gene, HLA-DR genotypes and certain autoimmune features in 102 patients with type I (insulin-dependent) diabetes. There was a significant decrease in the frequency of the 1:1 genotype (P = 0.008) and an increase in the 1:2 genotype (P = 0.03) of the BglII TcR polymorphism in the group of patients who developed type-I diabetes after the age of 20 years. This group of patients also showed an increased incidence of autoantibodies (especially islet cell antibody), a family history of diabetes and the presence of other autoimmune diseases. The frequency of this polymorphism in patients who developed type I diabetes before the age of 20 years was similar to a non-diabetic group. These results suggest that there are two genetically distinct groups of patients with type I diabetes. HLA-DR3 and HLA-DR4 genotypes were also increased in the diabetic patients but no significant difference was observed between HLA-DR genotypes, the TcR-C beta genotypes, the age of diagnosis or with other autoimmune features. Patients developing type I (insulin-dependent) diabetes after the age of 20 years have an additional genetic susceptibility for diabetes associated with the TcR-C beta gene.

Adolescent↗

Carrier estimations in Duchenne muscular dystrophy families in Northern Ireland using RFLP analysis.

Intragenic RFLP analysis was used to provide carrier risk estimations on 100 possible female carriers from 22 Duchenne muscular dystrophy families. This enabled 78% of possible carriers to be assigned high or low risks (greater than 90% or less than 10%) as opposed to 26% assigned low risk on pedigree data alone. When a single polymorphism is not informative the use of haplotype analysis for carrier estimations is illustrated for one family.

Computers↗

Linkage disequilibrium and CF allele segregation analysis in cystic fibrosis families in Northern Ireland.

Linkage disequilibrium and cystic fibrosis (CF) allele segregation were analysed in 46 CF families in Northern Ireland. The smaller (+) allele of the KM19/PstI polymorphism and the larger (-) allele of the XV-2c/TaqI polymorphism showed marked linkage disequilibrium with CF. This information can be used to alter the risk of an individual being a carrier of CF away from the expected population risk of 1 in 20. The high-risk genotypes K+K+ or X-X- have a risk of 1 in 10 and the low-risk genotypes K-K- or X+X+ have a risk of 1 in 50. A study of the segregation of CF alleles in the 46 families, using KM19 and Xv-2c, showed preferential inheritance of the paternal (79%), as opposed to the maternal (21%), CF allele by the heterozygous carriers. A mechanism that might explain this observation is discussed.

Alleles↗

T cell receptor beta chain polymorphisms are associated with cystic fibrosis.

The BglII polymorphism near the constant region of the T cell receptor beta chain (TCR c beta) has been investigated in normal controls, patients with cystic fibrosis (CF), and CF carriers. A significant increase was found in the frequency of the 10.0:9.2 kb heterozygous genotype in the CF carrier group (71%) as compared with normal controls (44%) (p = 0.005). Patients with CF also showed an increased frequency of the heterozygous genotype but this was not significant. These results represent a previously unreported disease association and suggest that there may be some form of epistatic interaction between the CF gene and the TCR beta genes such that the double heterozygote is immunologically advantaged.

Cystic Fibrosis↗

Characterization of human skin fibroblast extracellular proteins by two-dimensional polyacrylamide gel electrophoresis.

Human skin fibroblasts secrete over 50 proteins into the culture medium. In this paper these are characterised using two-dimensional polyacrylamide gel electrophoresis and peptide mapping of proteins metabolically labelled in the presence and absence of tunicamycin. Thirty of these proteins have been shown to be N-glycosides, 4 are O-glycosides and 10 are not glycosylated. Of the major proteins, groups 1-4 have previously been shown to be fibroblast specific. Peptide mapping and tunicamycin treatment has identified that groups 1 and 2, and 3 and 4 are closely related and that groups 1 and 3 arise by N-glycosylation of 2 and 4, respectively. The unglycosylated precursor forms of several other proteins have also been identified. This approach to the analysis of protein secretion provides an abundance of information on many proteins simultaneously and can be used to assess the changes in protein secretion associated with development, and to identify extracellular growth factors and other regulatory proteins.

Adult↗

The relationship between retrospective premenstrual symptom reporting and present oral contraceptive use.

The premenstrual assessment form (PAF) was used to assess the degree and type of premenstrual changes reported by 101 oral contraceptive users and 149 non-users (aged 18-45 yr) attending general health and gynaecology clinics. Women using oral contraceptives did not complain of fewer or less severe symptoms overall, but their severity scores on the subscales of premenstrual anxiety, fatigue, low mood, water retention, and impaired social functioning were significantly lower than those of non-users. The duration of oral contraceptive use and the type of preparation (combined or phased) taken were not related to the degree of premenstrual change reported. Complaints of symptoms beginning more than two days before menstruation were less frequently reported by pill-users (p less than 0.01) and were associated with a greater severity of all types of premenstrual change (p less than 0.0001). Women who had experienced difficulties tolerating oral contraceptives reported a greater number of moderate/severe premenstrual changes (p less than 0.0001).

Adolescent↗

Studies on the possible role of brain 5-HT systems and adrenocortical activity in behavioural responses to nicotine and diazepam in an elevated X-maze.

Subchronic (6 days) but not acute injections of nicotine (0.4 mg/kg SC) increased spontaneous activity (P less than 0.01) in an elevated X-maze composed of two open and two enclosed runways. Neither acute nor subchronic nicotine altered significantly the ratio of open:enclosed runway entries (O/E ratio). Diazepam (5 mg/kg PO) had no significant effects on spontaneous activity but increased the O/E ratio (P less than 0.05). Acute nicotine increased (P less than 0.01) whereas subchronic nicotine caused a small decrease (P less than 0.05) in the plasma corticosterone concentration. Both acute and subchronic diazepam decreased the levels of the hormone (P less than 0.01 and P less than 0.05, respectively) although the reduction elicited by chronic diazepam was less than that caused by acute diazepam (P less than 0.05). In the experiments with diazepam the plasma corticosterone concentration correlated negatively with the O/E ratio (r = -0.58; P less than 0.05), whereas in the experiments with nicotine plasma corticosterone correlated negatively (r = -0.46; P less than 0.05) with enclosed runway entries. Nicotine injections were associated with a regionally-selective reduction in the 5-hydroxyindole acetic acid (5-HIAA) concentration in the hippocampus (P less than 0.05) and a reduction in hippocampal 5-hydroxytryptamine (5-HT) which approached statistical significance. Chronic, but not acute, diazepam increased (P less than 0.01) hypothalamic 5-HT. The changes in 5-HT and 5-HIAA did not appear to be directly related to the behavioural or adrenocortical responses to either of the drugs.

Animals↗

Behavioural and adrenocortical responses to nicotine measured in rats with selective lesions of the 5-hydroxytryptaminergic fibres innervating the hippocampus.

The effects of acute and subchronic (7) injections of nicotine (0.4 mg kg-1, s.c.) and of selective lesions of the 5-hydroxytryptaminergic (5-HTergic) pathways innervating the hippocampus on the spontaneous behaviour of rats in an elevated X-maze composed of two open and two enclosed runways have been examined. Subchronic, but not acute, nicotine increased total spontaneous activity. Neither acute nor subchronic nicotine altered the ratio of open:closed runway entries. Destruction of the 5-HTergic pathways innervating the hippocampus with 5,7-dihydroxytryptamine caused a reduction in the ratio of open:enclosed runway entries. Acute, but not subchronic, nicotine caused a significant increase in plasma corticosterone. The lesion had no effects on the plasma levels of this hormone. No significant interactions between the lesion and the responses to nicotine were observed. The data failed to provide any evidence that hippocampal 5-HTergic systems may be implicated in the effects of nicotine on the spontaneous behaviour of the rat.

5,7-Dihydroxytryptamine↗

Differences in proteins secreted by human fibroblasts and muscle cells in culture.

Cell cultures of human skin fibroblasts, myoblasts, and fused muscle cells were grown in the presence of [14C]leucine or a mixture of [14C]amino acids. The proteins synthesised and secreted or leaked into the culture medium during radio-labelling were separated by one- and two-dimensional PAGE and detected by fluorography. Four major bands of Mr 54 kD, 52 kD, 51 kD, and 49 kD were present at greatly increased concentration in fibroblast media. These fibroblast-specific polypeptides can be readily detected in myoblast/fibroblast cocultures with fibroblast content as low as 5%.

Amino Acids↗

Operationalizing the concept of sexuality comfort: applications for sexuality educators.

Thirty-two high school and college educators participated in a study designed to operationalize the concept of sexuality comfort. Research questions asked were: "What is the nature of sexuality comfort?" and "Can the concept, of sexuality comfort be defined operationally?" An interview guide developed with input from an expert panel of health/sexuality educators and semanticists facilitated data collection. Data were categorized and tabulated through a systematic process. This coding process, performed by independent coders, yielded 97.2% reliability. Based on the results, an operational definition of sexuality comfort was delineated. Because an operational definition is one which tells what to do to experience the thing defined, the operational definition of sexuality comfort has immediate practical applications to preparation programs for prospective sexuality educators as well as those currently working in the field.

Attitude↗