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Biomedical subjects

C M Clark

Publications and source records attributed to C M Clark.

At least 109 records · Page 6Linked to original sources
PubMed1991

Linkage analysis of familial Alzheimer disease, using chromosome 21 markers.

Chromosome 21 markers were tested for linkage to familial Alzheimer disease (FAD) in 48 kindreds. These families had multiple cases of Alzheimer disease (AD) in 2 or more generations with family age-at-onset means (M) ranging from 41 to 83 years. Included in this group are seven Volga German families which are thought to be genetically homogeneous with respect to FAD. Autopsy documentation of AD was available for 32 families. Linkage to the 21 q11-q21 region was tested using D21S16, D21S13, D21S110, D21S1/S11, and the APP gene as genetic markers. When linkage results for all the families were summed, the LOD scores for these markers were consistently negative and the entire region was formally excluded. Linkage results were also summed for the following family groups; late-onset (M greater than 60), early-onset (M less than or equal to 60), Volga Germans (M = 56), and early-onset non-Volga Germans (M less than or equal to 60). For the first three groups, LOD scores were negative for this region. For the early-onset non-Volga German group (six families), small positive LOD scores of Zmax = 0.78 (recombination fraction theta = .15), Zmax = 0.27 (theta = .15), and Zmax = 0.64 (theta = .0), were observed for D21S13, D21S16, and D21S110, respectively. The remainder of the long arm of chromosome 21 was tested for linkage to FAD using seven markers spanning the q22 region. Results for these markers were also predominantly negative. Thus it is highly unlikely that a chromosome 21 gene is responsible for late-onset FAD and at least some forms of early-onset FAD represented by the Volga German kindreds.

Adult↗
PubMed1991

Ultraviolet versus non-ultraviolet light therapy for seasonal affective disorder.

Although light therapy has been shown to be effective in the treatment of seasonal affective disorder (SAD), little research has been done to determine which light wavelengths affect treatment outcome. In this triple crossover study the authors compared 1 week of light therapy in which bright (2500 lux), full-spectrum fluorescent light, with and without blockade of the ultraviolet (UV) spectrum, was used with a dim (500 lux) light control in 11 SAD patients. The dim light condition had no significant antidepressant effects as measured by the Hamilton Rating Scale for Depression (HAM-D), the Beck Depression Inventory (BDI), and an atypical depressive symptom (ATYP) score. The UV-light condition significantly reduced HAM-D, BDI, and ATYP scores, whereas the UV-blocked condition significantly reduced only the ATYP score. These results suggest that the UV-spectrum in light therapy may have a differential effect on typical and atypical symptoms in SAD.

Depressive Disorder↗
PubMed1990

Cortical glucose metabolism in Parkinson's and Alzheimer's disease.

Characteristic regional patterns of decreased cerebral glucose metabolism (rCMRG) have been described in a variety of neurodegenerative conditions associated with dementia. The present study was undertaken to determine whether the metabolic pattern in Parkinson's disease is altered by the presence of impaired cognitive function. Glucose metabolism was measured with positron emission tomography in 6 patients with Parkinson's disease and dementia (PDD), 8 patients with Parkinson's disease and normal cognition (PD), and 6 patients with Alzheimer's disease (AD). All AD patients subsequently had the diagnosis proven neuropathologically at autopsy. Correlation coefficients of the metabolic rates across 32 regions of interest were calculated between each pair of patients. Q-component analysis of the correlation matrix showed that the AD and PD groups formed two distinct clusters and that the PDD group had a metabolic pattern which was similar to that of the AD group. Comparison of standardized rCMRG values showed that the PDD group differed from the PD group in having significantly lower relative rCMRG in the left perirolandic and bilateral angular gyrus regions. There were no significant differences between the PDD and AD groups. These results suggest a similar pattern of cortical dysfunction in both Alzheimer's disease and in Parkinson's disease/dementia.

Aged↗
PubMed1990

Melatonin suppression in bipolar and unipolar mood disorders.

Nocturnal melatonin suppression to 500 lux light was studied during an acute episode of illness in 8 patients with bipolar disorder, 7 patients with unipolar depression, and 15 age-, sex-, and season-matched normal controls. Unipolar patients did not differ from controls in melatonin suppression. In contrast to previous studies, controls showed greater melatonin suppression than bipolar patients. Baseline melatonin concentration, however, was significantly lower in the bipolar group compared to the unipolar and control groups.

Bipolar Disorder↗
PubMed1990

Right and left orientation in children aged 5 to 13 years.

A 32-item test of right/left orientation was administered to 360 normal children, aged 5 to 13 years. The distribution of scores was tested to determine if parametric descriptive statistics were appropriate. As the distribution was multimodal, the test of normality was rejected. The three modes were consistent with a stage development theory, with the respective modes being consistent with (a) no understanding of right/left, (b) a personal or egocentric understanding of right/left, and (c) a generalization of right/left to external objects. Therefore, the data are presented in terms of the probability of obtaining a specific score at a given age. Scores were not found to be related to sex and were weakly, if at all, related to level of psychometric intelligence.

Adolescent↗
PubMed1990

Increased liver alanine in the tumour-bearing host. Altered levels of some enzymes involved in alanine metabolism.

A 2-fold increase in hepatic alanine concentration was observed in rats bearing a Walker 256 carcinoma growing sub-cutaneously. Decreases were observed in the activities of both cytosolic and mitochondrial isozyme forms of L-alanine-2-oxoglutarate aminotransferase. Activities of two enzymes involved in a secondary pathway of haem synthesis involving alanine, L-alanine-4,5-dioxovalerate aminotransferase and the NADP-requiring isozyme form of 4-oxo-5-hydroxyvalerate dehydrogenase were also reduced but there was no change in liver porphyrin concentration. L-alanine-glyoxalate aminotransferase activity was unaffected. The results are discussed in relation to the utilisation of alanine as a gluconeogenic substrate in the tumor-bearing host.

Alanine↗
PubMed1989

Evening urine cortisol excretion and DST results in depression and anorexia nervosa.

Cortisol determination in a single one-hour urine sample collected between 2200 h and 2300 h has been shown to identify accurately patients with Cushing's disease. To examine the usefulness of this procedure for identifying psychiatric patients with a pituitary-adrenal disturbance, we studied 17 drug-free depressed patients, 6 euthymic anorectic patients and 10 healthy volunteers. We found that there was good agreement between DST results and evening urine cortisol excretion in this sample (when cortisol levels were expressed as ng of cortisol per mg of creatinine), and that adopting as a criterion a urine cortisol value two standard deviations above the mean cortisol value of the controls predicts 74% of the dexamethasone suppression test (DST) results. We would like to suggest that this measure deserves further study as a potentially useful and simple alternative to the DST for identifying psychiatric patients with a pituitary-adrenal disturbance.

Adolescent↗
PubMed1989

Effect of morphine on cortisol and prolactin secretion in anorexia nervosa and depression.

Endogenous opioid peptides are involved in feeding regulation, and alterations in opioidergic regulation have been implicated in the pathophysiology of eating disorders. To investigate further this hypothesis, we conducted a placebo-controlled study of the effect of the opiate alkaloid morphine on cortisol and prolactin secretion in six patients with anorexia nervosa and six age-matched healthy volunteers, and compared the results with those obtained in nine depressed patients. Basal cortisol but not basal prolactin levels were elevated in patients with anorexia nervosa and patients with depression. Following the administration of morphine plasma concentrations of cortisol levels declined progressively and at a similar rate in all three groups. The prolactin response to morphine was attenuated significantly in patients with depression. Neither the cortisol and prolactin response to morphine in the anorectic patients nor the cortisol response in the depressed patients we observed in this study suggests altered opiate receptor sensitivity. However, the decreased prolactin response to morphine in depressed patients remains compatible with this hypothesis.

Adolescent↗
PubMed1988

Response of skeletal muscle RNA polymerases I and II to tumour growth.

The muscle wasting which occurs in animals bearing a transplantable tumour is accompanied by a decrease in the level of protein synthesis and a loss in RNA. This paper examines the behaviour of RNA polymerases I and II (EC 2.7.7.6) in nuclei isolated from skeletal muscle of rats bearing a Walker 256 carcinoma. Marked decreases were observed in template-engaged RNA polymerase I and II activities and in free RNA polymerase I activity. Free RNA polymerase II activity was unaltered. When assays were carried out at high (NH4)2SO4 concentration or in the presence of heparin the diminished RNA polymerase I activity was still apparent, but heparin and high ionic strength overcame the inhibition of RNA polymerase II. Loss of RNA polymerase I activity was associated with a decrease in the number of template-engaged enzyme molecules and in the polynucleotide elongation rate. The number of template-engaged RNA polymerase II molecules was unaltered by tumour growth, but the polynucleotide elongation rate was significantly reduced. No evidence was obtained for any alteration in ribonuclease activity in nuclei or whole muscles of tumour-bearing rats. These results demonstrate an effect of the tumor on transcription in skeletal muscle of its host.

Amanitins↗
PubMed1988

Brain glucose metabolism in neurologically normal patients with sickle cell disease. Regional alterations.

Neurologic dysfunction is a significant source of morbidity and mortality in the sickle cell diseases, occurring with a prevalence of 6% to 34%. Because changes in brain glucose metabolism may precede gross functional or morphologic alterations, we recently applied the technique of positron emission tomography with fluorodeoxyglucose F 18 in an exploratory study to compare six patients with sickle cell disease without prior neurologic abnormalities (and with normal cranial computed tomographic scans) with six healthy age-matched controls, with respect to overall and regional cerebral metabolic rates for glucose. We found no significant difference in the global metabolic rates for the two groups. However, we observed an unusual clustering of abnormal regional cerebral metabolic rates for glucose in the frontal lobes of these subjects. These results support previous observations that frontal lobe involvement may be quite prevalent in sickle cell disease, even among individuals with normal computed tomographic scans.

Adult↗
PubMed1988

Genetic linkage studies in Alzheimer's disease families.

Alzheimer's disease is a devastating neurological disorder and the leading cause of dementia among the elderly. Recent studies have localized the gene for familial Alzheimer's disease to chromosome 21 in a series of early onset AD families (mean age of onset less than 60). Familial late onset AD (mean age of onset greater than 60) is a more common clinical form of the disorder. Thirteen families with multiply affected Alzheimer's disease family members were identified and sampled. Ten of these families were of the late onset Alzheimer's disease type. Simulation studies were used to evaluate the usefulness of these pedigrees in linkage studies in familial Alzheimer's disease. Linkage studies undertaken to test the localization of both early onset and late onset Alzheimer's disease families to chromosome 21 failed to establish linkage and excluded linkage from a large portion of the region where the early onset Alzheimer's disease gene was localized. These findings suggest that more than one etiology may exist for familial Alzheimer's disease and indicate the need for continued screening of the genome in familial Alzheimer's disease families.

Alzheimer Disease↗
PubMed1988

Regional cerebral glucose metabolism in identical twins.

The present study reports on the degree of similarity in regional cerebral glucose metabolism in seven sets of female identical twins. All scans were done with subjects at rest. Glucose metabolism was measured with positron emission tomography (PET). Significant intraclass correlations were found for the orbital and prefrontal cortex as well as the basal ganglia (caudate/putamen). It is suggested that these correlations reflect the functional aspects of these areas, namely attention and posturing movements.

Adult↗