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Biomedical subjects

N King

Publications and source records attributed to N King.

At least 91 records · Page 5Linked to original sources
PubMed1994

Genetic linkage evaluation of twenty-four loci in an eastern Canadian family segregating Darier's disease (keratosis follicularis).

BACKGROUND: Darier's disease (keratosis follicularis) is known to have a genetic cause as evidenced by its autosomal dominant transmission in families. The gene causing this disease has not been discovered. OBJECTIVE: During an ongoing linkage study of schizophrenia, a family segregating Darier's disease was found. This family is being studied in an attempt to locate prospective regions that may contain the Darier's disease gene. METHODS: Two genetic strategies are being employed: (1) testing candidate genes for the disorder and (2) scanning the entire genome with polymerase chain reaction-based microsatellite markers. RESULTS: Thirty-nine marker systems located on chromosomes 1, 2, 4, 5, 6, 9, 11, 12, 16, 17, 22, X, and Y have been genotyped. Slightly positive lod scores were achieved between six markers and Darier's disease. The remaining 33 markers were nonsegregating or indeterminate, or revealed an obligate recombinant. CONCLUSION: Linkage analysis can lead to localization of the gene causing Darier's disease. In these preliminary studies low positive lod scores were obtained, potentially pointing to the chromosomal location of the Darier's disease gene.

Chromosome Mapping↗
PubMed1994

Analysing general practitioners' referral decisions. I. Developing an analytical framework.

Despite a large volume of research, understanding the influences on general practitioner referral behaviour remains limited. This paper argues for the value of an approach to this area based on the analysis of individual referral decisions, rather than aggregated referral statistics. A framework for analysing referral decisions is described, developed from a study that collected accounts of 167 referral decisions from 28 general practitioners. The framework enables referral decisions to be examined at three levels of analysis of increasing generality. It also encompasses factors that influence general practitioners against making a referral as well as those that influence them towards referral, as it was found that both types of influence can be discerned in most cases. The types of study in which the framework would be a useful analytical tool are discussed.

Adolescent↗
PubMed1994

Analysing general practitioners' referral decisions. II. Applying the analytical framework: do high and low referrers differ in factors influencing their referral decisions?

An analytical framework of the referral decision was applied to the question of whether general practitioners (GPs) with relatively high and relatively low referral rates differed in the types of factors that influenced their referral decisions. Interview data from six high referring and six low referring GPs were compared at all levels of the framework, using both quantitative and qualitative content analysis. High referrers were found to mention significantly more negative factors than low referrers, i.e. they referred 'in spite of' reasons against referral. In particular, they referred patients in spite of having doubts about treatment effectiveness. Low referrers mentioned factors related to interpersonal processes significantly more often than high referrers, for example, GP-patient communication as an influence. Possible interpretations of these findings are discussed.

Adolescent↗
PubMed1994

Analysis of new D4 dopamine receptor (DRD4) coding region variants and TH microsatellite in the Old Order Amish family (OOA110).

The candidate genes tyrosine hydroxylase (TH) and the dopamine D4 receptor gene (DRD4) are both located in the 11p15.5 region, thus creating strong interest in this region for genetic studies of bipolar affective disorder. It is conceivable that disregulation of the dopamine system could arise from genetic defects in DRD4 or TH, which in turn may lead to susceptibility to this disorder. We have begun our search for an autosomal linkage to bipolar affective disorder in the Old Order Amish (OOA110) with the 48 bp coding region polymorphism for DRD4. A small positive lod score of 1.16 was determined. A new polymerase chain reaction-based tetranucleotide repeat marker for the TH gene was investigated, and also had a small positive lod score of 0.63 at theta = 0.10. This finding replicates the small positive (lod = 0.42) RFLP results of Pakstis et al, (1991a). These two new markers were not able to provide statistically significant results, however their role as modifier genes in the pathogenesis of affective disorders cannot be excluded. Future studies that include the sequence variants within the 48 bp motif of the DRD4 coding region polymorphism, and possibly alternate definitions of the affective disorder phenotype, may provide more definitive answers.

Bipolar Disorder↗
PubMed1994

Immunohistochemical and biochemical analysis of the oestrogen regulated protein pS2, and its relation with oestrogen receptor and progesterone receptor in breast cancer.

AIMS: (i) To assess the validity of an immunocytochemical technique for detecting pS2 protein in paraffin wax embedded tissue; (ii) to provide further data on the relation between pS2 protein and oestrogen receptor (ER) and progesterone receptor (PgR). METHODS: Breast cancer excision biopsy specimens were obtained from 35 previously untreated patients. An immunoradiometric assay was compared with an immunohistochemical method for measuring pS2 protein. ER and PgR were measured in cytosol fractions by enzyme immunoassay and the relation between the presence of these receptors and pS2 protein was assessed before and after subdivision of the women into groups of over or under 50 years of age. RESULTS: A good correlation was seen between the immunoradiometric and immunohistochemical methods for pS2 protein measurement (r = 0.84; p = 0.0001). Log-transformed data showed a significant correlation between increasing values of ER and pS2 protein (r = 0.45; p = 0.006) and to a lesser extent between pS2 protein and PgR (r = 0.38; p = 0.03). Correlations were also shown between pS2+ and PgR+ status (p = 0.01), and between ER and PgR positivity (p = 0.05; Fisher's exact test). pS2+ protein status was only associated with ER+ status in patients aged 50 years or less. CONCLUSIONS: The two methods for pS2 analysis are virtually interchangeable. This provides strong support for using immunohistochemistry for pS2 in paraffin wax embedded tissue. The association with ER positivity and pS2+ protein status only in the premenopausal patients may be due to the higher levels of oestrogenic stimuli in that group.

Adult↗
PubMed1994

Cold-weather field feeding: an overview.

Extremely cold environments are a challenge to military field feeding operations due to freezing and inadequate intakes of rations and water. The U.S. Army Research Institute of Environmental Medicine conducted a series of three cold-weather field feeding studies to test, modify, and contribute data for the development of Cold-Weather Feeding Doctrine. Conclusions from these studies show that command emphasis is essential for ration and water storage and distribution to prevent freezing, and adequate ration and water consumption to prevent weight loss and dehydration. Since any ration mix can be configured to meet cold-weather feeding requirements, the decision of which ration to use should be based on logistical support and constraints, mission requirements, and water availability.

Dehydration↗
PubMed1993

Co-expression of an anion conductance pathway with Na(+)-glucose cotransport in rat renal brush-border membrane vesicles.

Brush-border membrane vesicles were prepared from superficial rat renal cortex by a Mg(2+)-precipitation technique. The initial (20 s) [14C]glucose uptake rate from solutions containing 100 mmol/l Na (salt) was found to be dependent upon the anion composition of the medium; in comparison to gluconate-containing medium (0.46 +/- 0.05 nmol/mg protein), Cl- accelerated the initial rate to 1.47 +/- 0.21 nmol/mg protein (n = 4 preparations, +/- SEM). This enhancement was reduced by 5-nitro-2-(3-phenylpropylamino)-benzoic acid (NPPB, 0.5 mmol/l), but was unaffected by 4,4'-diisothiocyanatostilbene 2,2'-disulphonate (DIDS, 0.5 mmol/l). When membrane vesicles were pre-equilibrated with 100 mmol/l K (salt) and 100 mmol/l mannitol and glucose uptake was measured from a solution containing 100 mmol/l Na gluconate and 100 mmol/l mannitol in the presence of 80 mumol/l valinomycin (to generate an outward K+ diffusion electrical p. d.), it was found that intravesicular KCl depressed the initial glucose uptake compared to K gluconate. NPPB (0.5 mmol/l) increased the initial glucose uptake with intravesicular KCl towards values seen in K gluconate vesicles. In conditions where the only driving force for glucose uptake was established by an inward anion gradient (Nao = Nai) it was found that inward Cl- gradients could drive uphill glucose transport and that this was sensitive to NPPB (0.5 mmol/l), but insensitive to DIDS. We conclude that a Cl- conductance co-exists with Na-cotransport in rat renal brush-border membrane vesicles prepared from superficial renal cortex and this may function to regulate the activity of electrogenic transport systems at this membrane.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1993

Nutrition issues of military women.

Nutritional data were collected from 147 female soldiers in four surveys (two field and two dining hall studies) conducted by the US Army Research Institute of Environmental Medicine and Letterman Army Institute of Research. The 49 female soldiers observed in the field studies had suboptimal mean energy (1751 kcal), protein (52.3 g), calcium (620 mg), and iron (11.8 mg) intakes. In addition, 54 female soldiers in the dining hall studies also had lower than desirable mean iron (16.2 mg) intakes. These data suggest that nutritional problems encountered by military women are similar to those faced by their civilian counterparts, based on NHANES II and CSFII reports. Although the impact of sporadic low nutrient intakes during short 10-14-day field training exercises may be of little consequence, this may be significant when inadequate intakes occur routinely or for extended periods during military conflicts. Viable solutions to the nutritional problems of military women could include ration supplementation and nutrition education.

Adolescent↗
PubMed1993

Antibody penetration of viable human cells. II. Anti-RNP antibodies binding to RNP antigen expressed on cell surface, which may mediate the antibody internalization.

As U1 small nuclear ribonucleoprotein (U1 snRNP2) has a crucial role in pre-mRNP splicing, the interaction of anti-RNP antibody with snRNP within viable lymphocytes may profoundly influence cell functions. We have shown that antibody can penetrate viable human lymphocytes, and anti-RNP antibodies enter more cells than other anti-nuclear antibodies or control IgG. In order to study the in vitro interaction of anti-RNP antibodies with viable cells, T lymphocytes were metabolically labelled with 35S-methionine, then incubated with the antibodies and washed. A set of 35S-labelled cell-associated snRNP polypeptides A, B'/B, C and D were found to bind to both monospecific human polyclonal anti-RNP IgG (human anti-RNP IgG) and a mouse monoclonal anti-RNP antibody (2.73), indicating that anti-RNP antibodies interacted with RNP antigen inside or/and on the surface of viable cells. To investigate antibody binding to RNP antigen on the cell surface, the cell surface proteins were either iodinated with 125I or the cells processed for immunoelectron microscopic studies after incubation with MoAb. At least seven 125I-labelled polypeptides on the cell surface were found to be immunoprecipitated by the anti-RNP MoAb which have similar molecular weights to U snRNP polypeptides 70K, A, B, D, E, F, and G. The immunoelectron microscopic studies showed that the gold particles formed clustered patches on the cell membrane. Further studies suggested that RNP antigen bound to the cell surface, and the RNP binding structure was probably a heterodimer receptor. This study provides evidence to suggest that anti-RNP antibody entry into viable cells may be mediated by interaction with RNP antigen expressed on the cell surface.

Animals↗
PubMed1993

Attenuation of colitis in the cotton-top tamarin by anti-alpha 4 integrin monoclonal antibody.

Recent studies have demonstrated the induced expression of endothelial adhesion molecules including E-selectin (also called endothelial leukocyte adhesion molecule-1), vascular cell adhesion molecule and intercellular adhesion molecule in actively involved mucosa of patients with ulcerative colitis and Crohn's disease. Similar induction has been demonstrated in the colon of the Cotton-top tamarin (CTT), a New World primate that experiences a spontaneous acute and chronic colitis resembling ulcerative colitis. To assess the potential importance of leukocyte adhesion as a necessary step in acute colitis, the effect of parenteral mAb directed against adhesion molecules on CTT colitis was evaluated in placebo-controlled blinded trials. Serial administration of either of two anti-E-selectin mAb designated BB11 and EH8 effectively coated endothelial surfaces expressing this vascular adhesion molecule. Although colitis activity was slightly diminished after the 10-d treatment period in CTT receiving either BB11 or EH8, this reduction was not significantly different than that seen in animals given a placebo control when assessed by a previously validated standardized scale of inflammatory activity: mean histologic activity grade 2.2 +/- 0.2 pretreatment vs 1.5 +/- 0.5 posttreatment in group receiving mAb and 2.1 +/- 0.1 pretreatment vs 1.3 +/- 0.5 posttreatment in the placebo group (P > 0.2). In contrast, administration of an anti-alpha 4 integrin mAb designated HP1/2 that binds VLA4 (alpha 4 beta 1) and presumably alpha 4 beta 7 integrins resulted in significant attenuation of acute colitis when compared to both pretreatment activity index (P = 0.005) and the placebo control group (P < 0.01): mean histologic activity grade 1.6 +/- 0.3 pretreatment vs 0.2 +/- 0.1 posttreatment in the group receiving HP1/2 and 1.8 +/- 0.5 pretreatment and 1.2 +/- 0.2 posttreatment in the placebo control group. These studies using a model of spontaneous colitis in the CTT demonstrate the feasibility of modulation of leukocyte-vascular adhesion and/or other integrin-mediated events possibly including T cell aggregation and T cell-stromal interactions, as well as lymphocyte homing. These results suggest both that these processes are important and possibly essential elements in sustaining acute colitis and that their disruption may result in therapeutic benefit.

Animals↗
PubMed1993

Cold weather field evaluation of the 18-Man Arctic Tray Pack Ration Module, the meal, ready-to-eat, and the Long Life Ration Packet.

The Army Field Feeding System was evaluated for its ability to provide adequate nutrition and hydration during a 10-day cold weather field exercise. Soldiers consumed the 18-Man Arctic Tray Pack Ratio Module with either a wet-pack (Meal, Ready-to-Eat) or a dehydrated (Long Life Ration Packet) individual ration. Both feeding regimens were acceptable, meeting protein and micronutrients requirements. However, the soldiers consumed only 70% of their energy requirement, thus losing an average of 0.9% of body weight. This weight loss, although not excessive, underscores the importance of maintaining an adequate food intake during extended cold weather military field operations.

Adolescent↗
PubMed1992

Expression of vascular adhesion molecules in inflammatory bowel disease.

The expression of the vascular adhesion molecules ELAM-1 (endothelial leukocyte adhesion molecule 1) and VCAM-1 (vascular cell adhesion molecule 1) was evaluated in colonic mucosa of patients with inflammatory bowel disease and normal controls by immunocytochemistry. VCAM-1 was found to be constitutively expressed in lymphoid aggregates in normal colonic mucosa and was not significantly enhanced or altered in distribution in mucosa of patients with inflammatory bowel disease regardless of the activity of the inflammatory process. In contrast, ELAM-1 was not detected by these techniques in normal colonic mucosa (n = 11) or in colonic mucosa of patients with inflammatory bowel disease which was either uninvolved or quiescent (n = 30). However, high levels of ELAM-1 were consistently found on endothelial surfaces in association with active inflammation in affected areas of colonic mucosa in patients with either ulcerative colitis (n = 27) or Crohn's colitis (n = 9). In addition, ELAM-1 appeared to be present within neutrophils which had migrated into crypt abscesses in affected mucosa. Similar analysis was carried out in the cotton-top tamarin (CTT), a primate that experiences an idiopathic chronic diffuse colitis resembling human ulcerative colitis. Although anti-human VCAM-1 antibodies did not react with the CTT, anti-human ELAM-1 stained endothelial surfaces in mucosal biopsies from CTT with active colitis. No ELAM-1 was identified in mucosa of CTT in which colitis activity was quiescent. Thus ELAM-1 is expressed on colonic endothelial surfaces in association with inflammation and may play an important role in facilitating leukocyte migration into sites of active IBD involvement.

Cell Adhesion Molecules↗
PubMed1992

An endocrine and pharmacokinetic study of four oral doses of formestane in postmenopausal breast cancer patients.

43 postmenopausal breast cancer patients were treated orally with the aromatase inhibitor formestane (4-hydroxyandrostenedione) at daily doses of 62.5, 125, 250 or 500 mg for 4 weeks followed by 250 mg daily for a further 4 weeks. For some patients, 62.5 mg did not suppress serum oestradiol levels maximally. The doses of 250 and 500 mg did not differ in their effectiveness. Oestrone levels were suppressed by all doses of formestane but no consistent changes of aldosterone, cortisol or 17-hydroxyprogesterone occurred. Serum levels of sex hormone binding globulin fell by about 15% during treatment with 250 mg formestane reflecting its minor androgenic activity. The maximum concentration and area under the curve of serum formestane levels after the first dose varied in an approximately linear manner with dose. It is concluded that formestane is an effective, specific suppressant of oestradiol levels via the oral route requiring no more than 250 mg to be given daily.

Administration, Oral↗
PubMed1992

Comparison of four immunochemical methods for the measurement of oestrogen receptor levels in breast cancer.

Four methods of assessing oestrogen receptor (ER) status were compared in 33 patients with operable primary breast cancer. The methods used to assess the ER status were immunocytochemical assay (ER-ICA) of frozen sections, fine needle aspirates and imprint material and enzyme immunoassay (ER-EIA) of tumour tissue. A mean overall ER positivity of 45% (15 out of 33), 41% (13 out of 32) and 21% (six out of 29) was obtained by immunocytochemical (ER-ICA) staining of frozen sections, fine needle aspirates and tumour imprints, respectively, and a mean overall ER positivity of 42% (14 out of 33) was obtained by ER-EIA. The concordance of ER positivity in pairs of data obtained from different method combinations was found to range between 72 and 91%. However, statistically there was no significant difference between the four methods on the basis of the data obtained. Good comparability has been shown between the three tissue analyses and therefore the method of choice is technically not immediately apparent.

Biopsy, Needle↗