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Biomedical subjects

N King

Publications and source records attributed to N King.

At least 73 records · Page 4Linked to original sources
PubMed1996

Genetic variant near cytosolic phospholipase A2 associated with schizophrenia.

Two studies were undertaken to determine a possible genetic basis for alterations in phospholipid metabolism in schizophrenia. Initial results demonstrated an association in 65 schizophrenics compared with a matched normal control population. A follow-up haplotype relative risk study of 44 triads (mother, father, affected offspring), confirmed the results seen in the association study. Results suggest that a genetic variant near the promotor region of the gene for cytosolic phospholipase A2, the rate-limiting enzyme in the synthesis of prostaglandins from arachindonic acid, is associated with schizophrenia.

Female↗
PubMed1996

Identification of a second human acetyl-CoA carboxylase gene.

Acetyl-CoA carboxylase (ACC), an important enzyme in fatty acid biosynthesis and a regulator of fatty acid oxidation, is present in at least two isoenzymic forms in rat and human tissues. Previous work has established the existence of a 265,000 Da enzyme in both the rat and human (RACC265; HACC265) and a higher-molecular-mass species (275,000-280,000 Da) in the same species (RACC280; HACC275). An HACC265 gene has previously been localized to chromosome 17. In the present study, we report cloning of a partial-length human cDNA sequence which appears to correspond to HACC275 and its rat homologue, RACC280, as judged by mRNA tissue distribution and cell-specific regulation of mRNA/protein expression. The gene encoding this isoenzymic form of ACC has been localized to the long arm of human chromosome 12. Thus, ACC is represented in a multigene family in both rodents and humans. The newly discovered human gene and its rat homologue appear to be under different regulatory control to the HACC265 gene, as judged by tissue-specific expression in vivo and by independent modulation in cultured cells in vitro.

Acetyl-CoA Carboxylase↗
PubMed1996

Influence of anastrozole (Arimidex), a selective, non-steroidal aromatase inhibitor, on in vivo aromatisation and plasma oestrogen levels in postmenopausal women with breast cancer.

The effect of anastrozole ('Arimidex', ZD1033), a new, selective, non-steroidal aromatase inhibitor on in vivo aromatisation and plasma oestrogen levels was evaluated in post-menopausal women with breast cancer. Twelve patients progressing after treatment with tamoxifen were randomised to receive anastrozole 1 mg or 10 mg once daily for a 28 day period in a double-blinded crossover design. In vivo aromatisation and plasma oestrogen levels were determined before commencing treatment and at the end of each 4-week period. Treatment with anastrozole 1 and 10 mg reduced the percentage aromatisation from 2.25% to 0.074% and 0.043% (mean suppression of 96.7% and 98.1% from baseline) and suppressed plasma levels of oestrone, oestradiol and oestrone sulphate by > or = 86.5%, > or = 83.5% and > or = 93.5% respectively, irrespective of dose. Notably, several patients had their oestrone and oestradiol values suppressed beneath the sensitivity limit of the assays. In conclusion, anastrozole was found to be highly effective in inhibiting in vivo aromatisation with no difference in efficacy between the two drug doses. Contrary to previous studies on other aromatase inhibitors, this study revealed an internal consistency between the percentage aromatase inhibition and suppression of plasma oestrone sulphate.

Anastrozole↗
PubMed1996

Assessment of dietary intakes of cadets at the US Military Academy at West Point.

OBJECTIVE: A study was conducted at the US Military Academy, West Point, NY, to assess the nutritional adequacy of menus and dietary intakes of the cadets and to determine the effect of the optional weekday evening meal policy on nutrient intakes. METHODS: Dietary intakes were obtained over a 7-day period using a diary-interview technique. Volunteer cadets, 118 males and 86 females, recorded their own intakes and were interviewed by dietitians to verify food records. Cadets were categorized by gender and divided into three groups based on whether they consumed 0-1, 2-3, or 4-5 weekday evening meals in the Cadet Mess. RESULTS: Multivariate methods were used to assess compliance with Military Recommended Dietary Allowances (MRDA) and nutrient densities as well as the role of gender, number of weekday evening meals consumed in the West Point Cadet Mess, and the use of nutritional supplements during the study week. The number of weekday evening meals consumed in the Cadet Mess, was positively correlated with the nutrient intakes of the cadet groups. The female 0-1 group had the highest proportion of individuals with mean intakes providing < 70% MRDA for vitamin B6, folate, vitamin A, magnesium, or zinc. Snacks provided from 24% to 32% of the energy intakes of the female groups and were often substituted for meals, particularly by cadets who ate the fewest meals in the Cadet Mess. CONCLUSIONS: Diet counseling is recommended to help these cadets choose more nutritious meals and snacks. University and college students that choose not to purchase some of their meals from campus dining facilities could have similar dietary intake patterns and nutritional shortcomings.

Adolescent↗
PubMed1996

Linkage analysis between schizophrenia and the Darier's disease region on 12q.

There have been reports of an association between Darier's disease, an autosomal dominant genodermatosis, and psychiatric illness. Recently the gene causing Darier's disease has been mapped to an area on 12q, between D12S58 and D12S84. The findings of linkage analysis of 4 markers in the Darier's disease region on 12q in five families segregating schizophrenia are presented. They fail to support close linkage between schizophrenia and the Darier's disease region on 12q.

Adult↗
PubMed1996

Accuracy of four commercial systems for identification of Burkholderia cepacia and other gram-negative nonfermenting bacilli recovered from patients with cystic fibrosis.

Burkholderia cepacia has recently been recognized as an important pathogen in chronic lung disease in patients with cystic fibrosis (CF). Because of the social, psychological, and medical implications of the isolation of B. cepacia from CF patients, accurate identification of this organism is essential. We compared the accuracies of four commercial systems developed for the identification of nonfermenting, gram-negative bacilli with that of conventional biochemical testing for 150 nonfermenters including 58 isolates of B. cepacia recovered from respiratory secretions from CF patients. The accuracies of the four systems for identifying all nonfermenters ranged from 57 to 80%, with the RapID NF Plus system being most accurate. The accuracies of these systems for identifying B. cepacia ranged from 43 to 86%, with the Remel system being most accurate. Depending on the commercial system, from two to seven isolates were misidentified as B. cepacia. The relatively poor performance of the commercial systems requires that identification of certain nonfermenters be confirmed by conventional biochemical testing. These organisms include B. cepacia, Burkholderia sp. other than B. cepacia, and infrequently encountered environmental species (Pseudomonas and Flavobacterium species). In addition, conventional biochemical testing should be done if a commercial system fails to assign an identification to an organism. Confirmatory testing should preferably be performed by a reference laboratory with experience in working organisms isolated from CF patients.

Bacteriological Techniques↗
PubMed1996

Dopamine D4 receptor gene polymorphism is associated with attention deficit hyperactivity disorder.

Dopamine is believed to play a major role in the manifestation of attention deficit hyperactivity disorder (ADHD), which affects 3-6% of school-age children and shows evidence of familiarity. The dopamine D4 receptor, which is preferentially distributed in cortical and limbic regions of the brain, is currently of major interest because of the high degree of functionally relevant variability in its gene (DRD4), and the association of this gene with Novelty Seeking behavior. We examined the variability in the length of a region of DRD4 that contains a 48-bp repeat sequence in children with ADHD and controls matched for ethnicity. ADHD children differed from controls in that the 7-fold repeat form of DRD4 occurred significantly more frequently than in the control sample. This form of the receptor has previously been shown to mediate a blunted intracellular response to dopamine. Although ADHD is likely to be multifactorial in its etiology and its heritability is likely to be polygenetic, the present findings suggest that polymorphic variation in the gene encoding the D4 dopamine receptor may be a contributing factor in the expression of symptoms associated with ADHD.

Attention Deficit Disorder with Hyperactivity↗
PubMed1996

DRD2, DRD3 and 5HT2A receptor genes polymorphisms in obsessive-compulsive disorder.

We performed an association analysis of the DRD2, DRD3 and 5HT2A genes polymorphisms in 67 Obsessive-Compulsive Disorder (OCD) patients and 54 healthy controls. There were no statistically significant differences in genotype or allele frequencies for any of the polymorphisms studied between OCD subjects and controls. For the subgrouped analysis, no results were significant after correction for multiple testing, although homozygosity of DRD2/A2A2 in subjects displaying vocal or motor tics approached significance compared to controls (Fisher exact test, P = 0.008). Our results may follow the notion that OCD patients with tics represent a different genetic subtype of the disease.

Adolescent↗
PubMed1995

Genetic linkage for Darier disease (keratosis follicularis).

Darier disease is an autosomal dominant skin disorder characterized by abnormal keratinocyte adhesion. Recent data have provided evidence for linkage of the Darier disease locus to 12q23-24.1 in British families. We have carried out linkage analysis using the 12q markers D12S58, D12S84, D12S79, D12S86, PLA2, and D12S63 in 6 Canadian families. Pairwise linkage analysis generated positive lod scores at all 6 markers at various recombination fractions, and each family showed positive lod scores with more than one marker. The peak lod score in the multipoint analysis (Zmax) was 5.5 in the interval between markers D12S58 and D12S84. These positive lod scores in North American families of varied European ancestry confirm the location of the Darier disease gene, and suggest genetic homogeneity. The future identification and sequencing of the gene responsible for Darier disease should lead to improved understanding of the disease and of keratinocyte adhesion in general.

Adolescent↗
PubMed1995

Exon 5 deletion variant estrogen receptor messenger RNA expression in relation to tamoxifen resistance and progesterone receptor/pS2 status in human breast cancer.

The exon 5 deletion splice variant of estrogen receptor (delta 5 ER), which in vitro is constitutively active in the absence of estrogens, may have a role in conferring both tamoxifen resistance and ER-related phenotype in breast cancer. We have investigated the expression of this variant in vivo (at the level of mRNA) in relation to known tamoxifen resistance and expression of the estrogen-regulated genes progesterone receptor (PgR) and pS2. The amount of delta 5 ER mRNA relative to wild type (WT) ER mRNA (% delta 5/WT) was assayed in 70 tamoxifen-resistant and 50 primary breast carcinomas using reverse transcription/PCR. Both WT and delta 5 ER mRNA were detected in the majority of tumors, although delta 5 ER was detected only in the presence of WT ER. Overall no significant difference was seen in % delta 5/WT ER between tamoxifen-resistant and primary control tumors (medians, 13 and 15%, respectively). Tumors in both control and resistant groups which expressed PgR/pS2 in the absence of measurable ER protein (ER- PgR+ and ER- pS2+) had significantly higher delta 5 ER mRNA levels compared with other phenotypes (P < 0.002). This association with ER-/pS2+ tumors has not been demonstrated previously. In ER+ tumors which expressed pS2, significantly greater delta 5 ER mRNA expression was observed in tamoxifen-resistant compared with control tumors (P = 0.05). A similar although nonsignificant trend was observed in ER+ PgR+ tumors. While delta 5 ER mRNA is unlikely to be responsible for tamoxifen resistance in most breast cancers, elevated delta 5 ER mRNA levels may be important in some tumors, especially those which continue to express high levels of PgR/pS2.

Adult↗
PubMed1995

Factors associated with coping in persons undergoing alcohol and drug detoxification.

In order to identify factors associated with the coping styles of detoxifying alcohol and drug patients, the coping styles of 137 alcohol and drug patients drawn from three city, suburban, and rural rehabilitation programs were examined in relation to various indices, including depression and anxiety. The results showed that depression was a moderately useful predictor of wishful thinking--the highest coping style utilized by patients. The relatively infrequent use of problem-focused coping across a range of stressful situations suggests that alcohol and drug patients may benefit from therapeutic programs designed to train them in the use of problem-focused coping strategies.

Adaptation, Psychological↗
PubMed1995

Recruitment for phase II of the Trials of Hypertension Prevention. Effective strategies and predictors of randomization. Trials of Hypertension Prevention (TOHP) Collaborative Research Group.

Phase II of the Trials of Hypertension Prevention is a multicenter, randomized, controlled trial designed to determine the efficacy of weight loss and reduction of sodium intake for lowering blood pressure and incidence of hypertension among persons with high-normal levels of blood pressure. The 2 x 2 factorial study design includes weight loss alone, restricted sodium intake alone, the combination of weight loss and sodium restriction, and a control group. Nine clinical centers used a variety of recruitment strategies to enroll 2382 participants over 17 months, which exceeded the sample size goal of 2250. Among randomized participants, 21% were minorities and 34% were women. Overall, direct mail generated the most randomized participants (73%), followed by community screening (12%) and media advertisement (11%). Referrals from community health care providers yielded few participants. Prescreening improved overall efficiency and reduced costs. Participants who were more likely to drop out voluntarily during the three-visit screening regimen tended to be younger, single, male, smokers, and less educated.

Adult↗
PubMed1995

Endocrine effects of GnRH analogue with low-dose hormone replacement therapy in women with endometriosis.

OBJECTIVE: GnRH analogues are being used increasingly for a number of oestrogen dependent conditions in women. The resultant profound hypo-oestrogenism is a disadvantage, however, but the preservation of pituitary sensitivity to negative feedback by oestradiol is not well defined. We have determined the effect on gonadotrophins and inhibin of GnRH analogue plus low-dose continuous combined hormone replacement therapy in comparison with GnRH analogue therapy alone. DESIGN: Randomized controlled trial. PATIENTS: Fifty premenopausal women with endometriosis randomized to treatment with goserelin alone (Group 1) or goserelin plus 17 beta-oestradiol and medroxyprogesterone acetate (Group 2). MEASUREMENTS: FSH, LH, oestradiol, oestrone, inhibin before and during treatment. RESULTS: Oestradiol and oestrone were suppressed in both groups, but Group 2 had significantly higher oestradiol during the hormone replacement therapy period. LH was suppressed in both groups. In Group 1, FSH levels recovered during treatment but, in contrast, in Group 2, FSH levels remained suppressed throughout treatment. Inhibin was significantly lower in Group 2, but not in Group 1, during treatment compared to pretreatment. CONCLUSIONS: Pituitary secretion of FSH appears to remain responsive to feedback control by oestradiol during GnRH analogue therapy and is incompletely suppressed, unlike LH which remains completely suppressed. The possible mechanisms for this are discussed.

Adult↗
PubMed1995

Test-retest reliability of the survey form of the Leyton Obsessional Inventory-Child Version.

The test-retest reliability of the survey form of the Leyton Obsessional Inventory-Child Version was examined over a 2-wk. interval. Three age groups of children participated in the study, 8- to 10-year-olds, 11- to 13-year-olds, and 14-to 16-year-olds (N = 106). For the total Obsessive scores, the test-retest Pearson correlation coefficients for the three age groups were .51, .75, and .83, respectively, which suggest that the temporal stability of the instrument is a function of age.

Adolescent↗
PubMed1995

Effects of reduced fat intake on serum lipids in healthy young men and women at the U.S. Military Academy.

To assess the benefits of Army nutrition initiatives reducing intakes of fat and cholesterol, the authors studied the dietary intakes of cadets at the U.S. Military Academy and compared these results and related nutritional indicators (body composition, serum lipid status) to data obtained one decade earlier. The regular Cadet Mess menu provided 16.6 MJ/day of energy with 34% derived from fat. Actual intakes, including supplements, averaged 14.9 +/- 2.9 and 9.7 +/- 2.1 MJ/day for 119 male and 86 female cadets, respectively. Most cadets derived < 35% of energy from dietary fat (11% from saturated fatty acids), representing a significant reduction since the previous study, in which nearly one-third of cadets received 40 to 45% of calories from fats; cholesterol intakes were markedly reduced. Serum cholesterol levels were approximately 7% lower, but were less affected than predicted by the reductions in fat and cholesterol intakes; serum low-density lipoprotein-cholesterol was also significantly reduced. Fasting serum insulin correlated with saturated fat intake in female cadets, indicating another health risk factor affected by intakes. The authors conclude that nutrition initiatives reducing energy derived from fats and total cholesterol intake have had a beneficial effect on the nutritional status of this fit young population.

Adult↗
PubMed1995

Treatment of school refusal. Strategies for the family physician.

Although school refusal is not a common problem, it causes extreme turmoil in families and affects psychological and social development of the growing child. Causes for school refusal are diverse. Careful assessment to clarify the function of the school refusal is critical for successful intervention. Effective management strategies have been developed and are described in more detail in a recent book by King, Ollendick, and Tonge.

Age Distribution↗