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Biomedical subjects

R A King

Publications and source records attributed to R A King.

At least 19 recordsLinked to original sources
PubMed1995

A labeled lines explanation of the perceived spatial frequency of moderate-, near-threshold- and zero-contrast spatial patterns.

We tested the predictions of a multiple-channels model about the appearance of spatial patterns. Specifically we tested how encoding the perceived spatial frequency of a near-threshold pattern compared with encoding of a zero-contrast or moderate-contrast pattern. For example, the model predicts that the mean perceived spatial frequency of a near-threshold pattern is a weighted average of the response to the stimulus and the noise. Six subjects used the method of adjustment procedure to match a peripherally viewed test stimulus (or a blank) with a foveally viewed grating. For near-threshold patterns we found a smooth perceived spatial-frequency function, with a smaller range of perceived spatial frequencies than obtained for 0.16 contrast patterns. These results are consistent with the predictions of the model: noise can affect the appearance of near-threshold and zero-contrast patterns.

Contrast Sensitivity↗
PubMed1995

Induction of micronucleus formation in mouse splenocytes by the soy isoflavone genistein in vitro but not in vivo.

The effects of genistein (one of the major soybean isoflavones), genistein (the glucosylated form of genistein) and etoposide (a topoisomerase 11 inhibitor) have been studied in mouse splenocytes in culture. Genistein (25 microM), genistein (25 microM) and etoposide (0.1 microM) all induced the production of large numbers of micronuclei; however, genistein at 12.5 or 2.5 microM had no clastogenic effect. In a second study, mice were gavaged with 20 mg genistein/kg body weight/day for 5 days (approximately equivalent to a 70 kg human consuming 2.8 kg soybeans/day) and the micronucleus frequency was determined. There was no observable increase in the micronucleus frequency even though the plasma genistein levels in the treated animals were found to be 9.2 +/- 2.0 microM compared with 0.1 +/- 0.0004 microM in the control animals. The results show that even though genistein is capable of inducing micronucleus formation, an event associated with genetic damage, plasma levels are unlikely to be sufficiently elevated to produce such an effect.

Administration, Oral↗
PubMed1995

Risperidone treatment of children and adolescents with chronic tic disorders: a preliminary report.

OBJECTIVE: The purpose of this trial was to investigate the short-term safety and efficacy of risperidone in the treatment of chronic tic disorders in children and adolescents. METHOD: This was an 11-week open-label trial and included seven subjects (five boys and two girls) with a mean age of 12.9 +/- 1.9 years. The sample included five patients with Tourette's syndrome and two with chronic motor tic disorder. The children were seen at baseline and for two follow-up visits. Three children had a comorbid diagnosis of obsessive-compulsive disorder (OCD). RESULTS: Clinical response, as measured by the Yale Global Tic Severity Scale and the Children's version of the Yale-Brown Obsessive Compulsive Scale, revealed a statistically significant reduction in tic scores ranging from 26% [corrected] to 66%. One of three children with comorbid OCD showed substantial improvement; the other two subjects showed no change. The most frequent side effect was weight gain, which ranged from 8 to 14 lb. CONCLUSIONS: Risperidone, a neuroleptic with both serotonin- and dopamine-blocking properties, appears to be effective in reducing tic frequency and intensity in children and adolescents with chronic tic disorders.

Adolescent↗
PubMed1995

An epidemiological study of trichotillomania in Israeli adolescents.

OBJECTIVE: To determine the prevalence of trichotillomania and comorbid psychopathology in nonreferred adolescents. METHOD: Using a questionnaire and interview, 794 Israeli 17-year-olds were screened for current and past hair-pulling and comorbid psychopathology. RESULTS: Eight current or past hair-pullers (5 male, 3 female) were identified, yielding a lifetime prevalence of hair-pulling of 1%. Four subjects reported current hair-pulling (point prevalence of 0.5%). None of these reported alopecia, distress, or tension before pulling; only two reported relief after pulling. Thus, none met the full DSM-III-R criteria for trichotillomania. Four subjects reported past but not current hair-pulling, with bald spots in two cases. Three of the four current hair-pullers had significant obsessive-compulsive symptoms, a significantly elevated rate compared to the entire screened population. Two subjects with obsessive-compulsive disorder also had generalized anxiety disorder and, in one case, chronic simple vocal tics. Hair-pullers did not differ significantly from non-hair-pullers in IQ, physical fitness, and overall competency, or prevalence of other comorbid disorders. CONCLUSIONS: In a community adolescent sample, only 25% of hair-pullers reported resulting bare spots and none endorsed both rising tension and subsequent relief. The prevalence of obsessive-compulsive symptoms was significantly elevated in these nonreferred hair-pullers.

Adolescent↗
PubMed1995

Fish oils modulate blood pressure and vascular contractility in the rat and vascular contractility in the primate.

The effect of dietary fish oils on development of hypertension and vascular response in vitro were studied in rats and a primate. Dietary fish oils (MaxEPA and an n-3 ethyl ester concentrate of higher EPA and DHA content) were administered to spontaneously hypertensive (SHR), stroke-prone spontaneously hypertensive (SHR-SP) and a backcross of SHR and Wistar Kyoto (SHR/WKY) rats from 4-16 weeks of age. Blood pressure was monitored during the feeding period and vascular responses measured in the aorta and mesenteric vascular bed in vitro. Depending on the strain of rat used and the composition of the fish oil the attenuation in blood pressure was 10-26 mmHg. Fish oils attenuated the response mediated by sympathetic nerve stimulation or intralumenal norepinephrine in the perfused mesenteric vascular bed preparation from the SHR. This attenuation was more pronounced for fish oils enriched with eicosapentaenoic acid and docosahexaenoic acid and was more prominent in the SHR and SHR/WKY backcross than it was in the SHR-SP. Prostanoid synthesis or nitric oxide modulation of alpha-adrenoceptor responses were shown not to be involved in the attenuation of vascular responses produced by fish oil. The maximum contraction of aortic ring preparations in response to norepinephrine (NE) was significantly smaller in SHR than WKY rats fed olive oil and for SHR rats maintained on fish oils the contraction was close to WKY olive oil values. Evidence was obtained also for a modulation of vasoconstrictor responses by dietary fish oils in the perfused mesenteric bed of the marmoset monkey.

Animals↗
PubMed1995

A gene causing Hermansky-Pudlak syndrome in a Puerto Rican population maps to chromosome 10q2.

Hermansky-Pudlak syndrome (HPS) is an autosomal recessive disorder that affects pigment production and platelet function and causes the deposition of a ceroid-like material in various tissues. Variability in the phenotype and the presence of several potential mouse models suggest that HPS may be a heterogeneous disorder. In order to identify a gene responsible for HPS, we collected blood samples from a relatively homogeneous population in Puerto Rico where the HPS carrier frequency is estimated to be 1 in 21. Analysis of pooled DNA samples allowed us to rapidly screen the genome for candidate loci, and significant evidence for linkage was detected for a marker on chromosome 10q. This region of the human genome is conserved syntenically with the region on mouse chromosome 19 where two possible mouse models for HPS, pale ear and ruby eye, are located. This linkage result was verified with additional markers, and a maximum LOD score of 5.07 at theta = .001 was calculated for marker D10S198. Haplotype analysis places the HPS gene in a region of approximately 14 cM that contains the markers D10S198 and D10S1239.

Albinism, Oculocutaneous↗
PubMed1995

Tyrosinase inhibition due to interaction of homocyst(e)ine with copper: the mechanism for reversible hypopigmentation in homocystinuria due to cystathionine beta-synthase deficiency.

Deficiency of cystathionine beta-synthase (CBS) is a genetic disorder of transsulfuration resulting in elevated plasma homocyst(e)ine and methionine and decreased cysteine. Affected patients have multisystem involvement, which may include light skin and hair. Reversible hypopigmentation in treated homocystinuric patients has been infrequently reported, and the mechanism is undefined. Two CBS-deficient homocystinuric patients manifested darkening of their hypopigmented hair following treatment that decreased plasma homocyst(e)ine. We hypothesized that homocyst(e)ine inhibits tyrosinase, the major pigment enzyme. The activity of tyrosinase extracted from pigmented human melanoma cells (MNT-1) that were grown in the presence of homocysteine was reduced in comparison to that extracted from cells grown without homocysteine. Copper sulfate restored homocyst(e)ine-inhibited tyrosinase activity when added to the culture cell media at a proportion of 1.25 mol of copper sulfate per 1 mol of DL-homocysteine. Holo-tyrosinase activity was inhibited by adding DL-homocysteine to the assay reaction mixture, and the addition of copper sulfate to the reaction mixture prevented this inhibition. Other tested compounds, L-cystine and betaine did not affect tyrosinase activity. Our data suggest that reversible hypopigmentation in homocystinuria is the result of tyrosinase inhibition by homocyst(e)ine and that the probable mechanism of this inhibition is the interaction of homocyst(e)ine with copper at the active site of tyrosinase.

Adolescent↗
PubMed1995

Serotonin and suicidality: the impact of fluoxetine administration. II: Acute neurobiological effects.

Despite the demonstrated anti-depressant efficacy of the selective serotonin reuptake inhibitors (SSRIs), increased suicidal ideation and/or agitation have been reported in a small proportion of individuals receiving fluoxetine or other SSRIs. Part II of this review examines fluoxetine's acute effects on serotonergic functioning. Although acute fluoxetine administration produces a short-term compensatory decrease in the firing of 5-HT neurons, the neurobiological data reviewed suggests that this decrease probably does not lead to an over-compensatory net decrease in 5-HT functioning. The implications of fluoxetine's complex effects on the 5-HT systems are discussed with respect to clinical practices and future research.

Animals↗
PubMed1992

The mouse pink-eyed dilution gene: association with human Prader-Willi and Angelman syndromes.

Complementary DNA clones from the pink-eyed dilution (p) locus of mouse chromosome 7 were isolated from murine melanoma and melanocyte libraries. The transcript from this gene is missing or altered in six independent mutant alleles of the p locus, suggesting that disruption of this gene results in the hypopigmentation phenotype that defines mutant p alleles. Characterization of the human homolog revealed that it is localized to human chromosome 15 at q11.2-q12, a region associated with Prader-Willi and Angelman syndromes, suggesting that altered expression of this gene may be responsible for the hypopigmentation phenotype exhibited by certain individuals with these disorders.

Amino Acid Sequence↗
PubMed1992

Risk factors for hypertension in Kimberley aborigines.

OBJECTIVE: To determine physical, biochemical and lifestyle factors associated with high blood pressure among Aborigines in the Kimberley region. DESIGN: Blood pressure and electrocardiographic (ECG) abnormalities in an age and sex stratified random sample of the Aboriginal population were related to other observations and measurements made at the same time specifically for the purpose of these comparisons. SETTING: A field study in which subjects were interviewed and measurements made mostly in community clinics. PARTICIPANTS: All 249 men and 241 women from the prevalence study were included although only complete data sets for the various comparisons were analysed. INTERVENTIONS: A sample of venous blood was obtained in addition to physical measurements and information at interview. MAIN OUTCOME MEASURES: Statistical analysis of the relationships between blood pressure or hypertension and alcohol consumption, plasma gamma-glutamyl transpeptidase (GGT) activity, use of tobacco, body mass index (BMI, kg/m2) and non-fasted plasma cholesterol level. Hypertension was defined as systolic blood pressure of 160 mmHg or greater or diastolic blood pressure of 95 mmHg or greater. RESULTS: High blood pressure in Aboriginal men below 30 years was associated both with current drinking status and with circulating GGT level. There was a positive association of diastolic hypertension with consumption of alcohol in middle aged men (30 to 49 years) and in older women. Drinking was highly prevalent among men, especially below 30 years, but was less prevalent among women. Both systolic and diastolic blood pressure were positively related to BMI across the population but obesity (BMI greater than or equal to 30 kg/m2) was highly prevalent only among middle-aged women. Both systolic and diastolic blood pressure were positively and strongly related to plasma cholesterol level independently of the latter's relationship to age and BMI. CONCLUSION: The high prevalence of drinking among Aboriginal men and of obesity among Aboriginal women involves a risk of hypertension. The association between plasma cholesterol and blood pressure in Aboriginal men and women may be relevant to the demonstrated link between systolic hypertension and ischaemic heart disease.

Adult↗
PubMed1992

Prevalence of hypertension in Kimberley aborigines and its relationship to ischaemic heart disease. An age-stratified random survey.

OBJECTIVE: To determine the age-specific prevalence of systolic and diastolic hypertension and of electrocardiographic abnormalities in the Aboriginal population of the Kimberley region of Western Australia. DESIGN AND SETTING: Age and sex stratified random samples of the Aboriginal population of the Kimberley region were selected and located. Measurements were made of systolic and diastolic blood pressure and electrocardiograms (ECG) were recorded. Hypertension was defined as a systolic blood pressure of 160 mmHg or greater or diastolic blood pressure of 95 mmHg or greater. ECG abnormalities were classified by the Minnesota system. PARTICIPANTS: Measurements were made on 249 men and 241 women distributed in seven age bands above 15 years and representing 78% of the selected men and 76% of the selected women. INTERVENTIONS: In addition to ECG and blood pressure, measurements were made of height and weight and information was obtained on medication, smoking, drinking and diet. A sample of venous blood was obtained. MAIN OUTCOME MEASURES: The data obtained on blood pressure, hypertension and ECG abnormalities were compared with existing data on Caucasian and Aboriginal Australians. RESULTS: Aboriginal men below the age of 30 years showed particularly high blood pressure compared with Caucasian men. The overall prevalence of hypertension in Aboriginal men 50 years of age and older was 45%. The prevalence of hypertension among Aboriginal women increased sharply from 35 years of age with a maximum between 55 and 65 years. The overall prevalence of hypertension in women 50 years of age and older was 50%. By regression, the average systolic/diastolic blood pressure at 40 years was 137/85 mmHg for men and 135/83 mmHg for women. ECG abnormalities indicating ischaemic heart disease (IHD) were more prevalent in both male and female Aborigines than had been found for Caucasians in 1966. In both sexes IHD and especially code 1.1 indicating myocardial infarct were associated with systolic hypertension. CONCLUSIONS: The prevalence of both systolic and diastolic hypertension and of probable IHD was two to three times higher in Kimberley Aborigines than in Caucasian Australians. ECG evidence of infarct was significantly related to systolic hypertension in both sexes.

Adolescent↗
PubMed1992

Molecular analysis of type I-A (tyrosinase negative) oculocutaneous albinism.

Type I oculocutaneous albinism (OCA) is caused by the reduction in or absence of activity of tyrosinase in melanocytes in skin, hair, and the eyes, the result of mutations of the tyrosinase gene. To date, a total of 22 unique mutations in the coding region of tyrosinase have been described in the literature. In this report we present 5 additional mutations of the tyrosinase gene associated with type I-A OCA in four individuals, including 2 missense, 1 frameshift and 2 nonsense mutations, and review the relevant literature on all published mutations. Analysis of the distribution of all identified missense mutations (n = 17) shows that most cluster in three areas of the gene and involve amino acids conserved between humans and the mouse. Two clusters involve the copper A and copper B binding sites and may disrupt the metal ion-protein interaction necessary for enzyme function. The third cluster in exon I could represent a functional domain important in enzyme function such as the tyrosine or the dihydroxyphenylalanine (DOPA) binding site of the enzyme. Small deletions or insertions resulting in frameshift mutations and nonsense mutations are distributed throughout the coding region and do not appear to cluster.

Albinism, Oculocutaneous↗
PubMed1992

Behavioral treatment of children and adolescents with trichotillomania.

Trichotillomania is a behavior disorder with onset generally in childhood, characterized by repetitive, compulsive pulling out of hair from the scalp, eyebrows, or other parts of the body, often leading to disfigurement. Trichotillomania tends to be persistent and is often resistant to counselling and standard psychiatric care. A systematic behavioral treatment program for children and adolescents and pilot findings with three patients are described. Methodological issues in relation to compliance and assessment are discussed. The relative safety and potential effectiveness of behavioral techniques suggest a useful role for this approach, perhaps in conjunction with pharmacological, family, and other treatment modalities.

Adolescent↗