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Biomedical subjects

C Clark

Publications and source records attributed to C Clark.

At least 181 records · Page 10Linked to original sources

Human immunodeficiency virus pseudotypes with expanded cellular and species tropism.

One mechanism for expanding the cellular tropism of a virus is through the formation of phenotypically mixed particles or pseudotypes, a process commonly occurring during viral assembly in cells infected with two or more viruses. We report here that dual infection of cells with human immunodeficiency virus (HIV) and a murine amphotropic retrovirus leads to the production of HIV pseudotypes that have acquired the host range of the amphotropic retrovirus and are capable of infecting not only CD4- human cells but also mouse cells. The replication of the HIV pseudotypes in the various CD4- cells was determined by measuring the appearance of HIV antigens in the supernatants, by cocultivation of CD4+ CEM cells with the infected CD4- cells, and in some cases by assaying the culture supernatants directly for infectious virus. Of the cells tested, human foreskin fibroblasts were the best host cells, and by in situ cytohybridization, we were able to document that all cells in the culture were infected. In addition, the temporal appearance of HIV-specific proteins in the HIV pseudotype-infected fibroblasts was similar to that seen in CD4+ CEM cells. If the human fibroblasts were first infected with the amphotropic retrovirus, they demonstrated the property of superinfection exclusion and were resistant to subsequent infection by the HIV pseudotype. In other cell lines, including the human glioblastoma-derived cell line U373MG, HeLa cells, BALB/c mouse embryo cells, and SC-1 wild mouse cells, although the HIV pseudotype infection appeared to be less efficient, substantial amounts of HIV were nevertheless produced. These results indicate that the HIV (amphotropic retrovirus) pseudotypes may be useful for studying the molecular biology of HIV infections in a wide range of cells.

Animals↗

An empirical model for analysing and interpreting ventricular measures.

Given the abundant and, at times, contradictory studies of ventricular enlargement in neurological and psychiatric disorders, the current study was carried out to provide an empirical basis for analysing and interpreting these measures. A sample of CT scans on 100 control subject was drawn from the files of the University of British Columbia Department of Radiology and 19 measures of ventricular and head diameter or area were made. The interrelationships of these measures were then examined using factor analytic procedures. Three ventricular dimensions were found. To validate these three dimensions, the relationship of each with age was examined and then the age-corrected scores of seven clinical groups were compared on each of these dimensions. The magnitude of the relationship between these dimensions and age was impressive and each dimension contributed unique information regarding these age-related changes. Moreover, the analysis of the clinical groups suggested that differential patterns of ventricular change were present dependent upon the disease. These results are discussed with a view to integrating the findings of previous studies and planning future studies.

Adult↗

Regional cerebral glucose metabolism in major depressive disorder.

Six subjects with DSM-III defined unipolar major depressive disorder had positron emission tomography scans using 18F-2-fluoro-2-deoxy-D-glucose (2FDG) before and after treatment with imipramine. Their 12 scans were compared to the scans of six controls matched for age. Significant reductions in metabolism for subjects in the depressed group were found on scans for both the anterior and right frontal regions. significant reductions in metabolism occurred more often in the right hemisphere than the left. No significant changes in metabolism could be attributed to imipramine. In addition, absolute metabolic rates were not related to the degree of depression pre- and post-treatment. The findings suggest that hypometabolism in the frontal cortex and right hemisphere may occur in major depressive disorders.

Adult↗

Family factors affecting adjustment in Japanese immigrant housewives.

Data obtained from 130 questionnaires distributed to immigrant Japanese housewives were analyzed to determine if family factors were associated with poor adjustment, and in particular with depressive symptoms. It was possible to identify women who had no major adjustment problems in adapting to life in Canada (n = 70), transitional adjustment problems (n = 30), late onset adjustment problems (n = 7) and chronic adjustment problems (n = 23). These categories were determined by self-report and validated by symptom identification. Style of marriage, communication with spouse and mother-child interactions were hypothesized to be related to adjustment problems. A 16 item questionnaire was developed to assess the degree to which these factors affected adjustment. The only factor which affected degree of adjustment was communication with the spouse. These results are discussed within the context of traditional hypotheses concerning adaptation to a new culture and the implication for treatment.

Acculturation↗

The fluid mechanics of a sac-type ventricular assist device.

Flow visualisation and velocity measurement studies have been carried out on the liquid side of a sac-type VAD. The objectives have been to identify both good (e.g. short residence times) and bad (e.g. high turbulence levels) flow characteristics. The flow was visualised using polystyrene micro-spheres illuminated with white light on selected transverse planes across the pumping chamber and its inlet and outlet connections. These results then served as a guide for velocity measurements using laser-Doppler anemometry. Flow tests were run using water or a water/glycerol mixture. Operating conditions were determined from the appropriate fluid mechanics modelling laws to ensure dynamical similarity. Initially, steady flow behaviour was investigated including the effects of removal and insertion of the tilting-disc inlet and outlet valves. In subsequent full pumping tests, using a pneumatic driver, regions of high shear, separation, and high turbulence intensity have been identified.

Blood Flow Velocity↗

Positron emission tomography in manganese intoxication.

We employed 6-fluorodopa to study the integrity of the nigrostriatal dopaminergic projection by positron emission tomography in 4 subjects with clinical features of mild parkinsonism caused by exposure to manganese. The 6-fluorodopa scans were normal. This finding suggests that in early manganism sufficient to cause parkinsonian deficits, damage may occur in pathways postsynaptic to the nigrostriatal system, probably involving striatal or pallidal neurons. Fluorodeoxyglucose scans showed decreased cortical glucose metabolism, the significance of which is discussed.

Adult↗

Linkage in a family with X-linked Charcot-Marie-Tooth disease.

The gene for the X-linked form of Charcot-Marie-Tooth disease (CMT Peroneal Muscular Atrophy, X-linked: McKusick No. 30280) has been shown in a single family to be linked to DXYS1 with a lod score of 4.55 at a recombination fraction of 0.03 and to PGK1 with a lod score of 3.34 at zero recombination. This is in agreement with previous work based on several families. Pooled data from this family and 7 previously reported families give a maximum lod score of 12.04 at theta max of 0.05 for linkage between CMTX and DXYS1 loci.

Charcot-Marie-Tooth Disease↗

Oral health promotion for institutionalised elderly.

The purpose of the present study was to develop and evaluate educational approaches specifically for improvement of oral hygiene behaviour amongst institutionalised elderly. A sample of 201 residents, 48-99 yr of age (mean age 82 yr), was selected from four different institutions in Lothian, Scotland. A clinical examination and a structured interview were conducted immediately before and 2 months after the termination of the programme. The four institutions were blind to the examiner and randomly allocated to a control group or one of the three programmes; 1) active involvement of staff only; 2) active involvement of residents only; 3) active involvement of both residents and staff. The programme comprised three 1-h sessions at monthly intervals in groups of five to six residents or members of staff. The analysis of the results showed poor oral health and oral hygiene, high objective need for oral care but low perceived need. The programme had little impact on most of the included variables and only about half of the participants remembered the programme 2 months after its termination. The implications of the study are that groups of elderly need to be differentiated further so that only well and not confused elderly participate in programmes such as this and less well and confused elderly receive regular professional support with oral hygiene.

Aged↗

Oesophageal ulcer caused by warfarin.

Oesophageal injury is a well recognized complication of certain oral medications but warfarin has not been implicated previously. We present a case of an oesophageal ulcer occurring in a patient with mitral regurgitation taking warfarin, and demonstrate a delayed oesophageal tablet transit time.

Drug Administration Schedule↗

Growth hormone response to growth hormone releasing factor in Alzheimer's disease.

Because of the well-established reduction in the concentration of somatostatin in several brain areas of patients with histologically verified Alzheimer's disease, we sought to determine if growth hormone (GH) secretion is altered in Alzheimer's disease. In order to study this, we assessed the GH response to growth hormone releasing factor (GRF) in 8 patients with Alzheimer's disease and 8 age-matched controls. Although there was no difference between the magnitude of the GRF-induced GH response (delta max GH response or area under the curve) between the Alzheimer's disease patients and the controls, the Alzheimer's patients exhibited a delayed GH response to GRF.

Aged↗

Sex differences in olfactory function in schizophrenia.

Olfactory identification and olfactory acuity were measured in 41 schizophrenic patients receiving neuroleptic medication and in 43 normal control subjects. The performance of the male schizophrenic patients was significantly lower than that of the female patients and the male and female normal control subjects. The last three subgroups performed at equivalent levels. These findings are discussed with respect to other reported sex differences in schizophrenia, including frequency of specific neurological signs and structural brain abnormalities, response to neuroleptic medication, and long-term outcome. The findings suggest that the sex of the patient may be a critical variable in understanding the processes of schizophrenia.

Adult↗

Regional cerebral glucose metabolism in three sets of identical twins with psychotic symptoms.

Three sets of young identical twins where at least one had a psychotic episode were assessed in terms of psychiatric and psychological status and integrity of cerebral structure and metabolism. The psychiatric diagnoses for each set were normal/schizophrenia, prodromal/schizophrenia and schizoaffective/schizoaffective. The latter two sets were re-examined two years after the initial assessment. The data are considered from a case study perspective. Reduced cerebral metabolism was found for at least one region on eight of nine scans of patients with a psychotic history. On seven of the nine scans, glucose metabolism in the orbital frontal cortex was reduced. These findings are discussed with respect to previous studies of glucose metabolism in patients with schizophrenia, metabolic similarities found in normal identical twins and the known functional specialization of the orbital frontal cortex.

Bipolar Disorder↗

The Consortium to Establish a Registry for Alzheimer's Disease (CERAD). Part I. Clinical and neuropsychological assessment of Alzheimer's disease.

The Consortium to Establish a Registry for Alzheimer's Disease (CERAD) has developed brief, comprehensive, and reliable batteries of clinical and neuropsychological tests for assessment of patients with the clinical diagnosis of Alzheimer's disease (AD). We administered these batteries in a standardized manner to more than 350 subjects with a diagnosis of AD and 275 control subjects who were enrolled in a nationwide registry by a consortium of 16 university medical centers. The tests selected for this study measured the primary cognitive manifestations of AD across a range of severity of the disorder, and discriminated between normal subjects and those with mild and moderate dementia. The batteries also detected deterioration of language, memory, praxis, and general intellectual status in subjects returning for reassessment 1 year later. Interrater and test-retest reliabilities were substantial. Long-term observations of this cohort are in progress in an effort to validate the clinical and neuropsychological assessments and to confirm the diagnosis by postmortem examinations. Although information on validation is limited thus far, the CERAD batteries appear to fill a need for a standardized, easily administered, and reliable instrument for evaluating persons with AD in multicenter research studies as well as in clinical practice.

Alzheimer Disease↗

Hemangioma of the liver: characteristics exhibited on a 0.15 Tesla scanner.

Twenty-two liver hemangiomas, initially diagnosed using ultrasonography, were imaged with a Picker 0.15 Tesla super-conducting scanner in order to (1) determine the reliability of spin-echo (SE) signal intensity measurements and the calculated T1 and T2 values of both normal tissue and hemangiomas and (2) assess the characteristics of hemangiomas as visualized by a low-field magnetic resonance imaging unit. Reproducible measurements of T1 values and signal intensities are possible (r = 0.93-0.99) but T2 values are less reproducible (r = 0.79) and more variable. T1 values provide the best discrimination between hemangiomas and normal liver (99% successful classification) followed by the SE signal intensity differences (94%). Signal intensity ratios and contrast-to-noise ratios of lesions compared with liver are similar to those of other studies. Most small hemangiomas exhibit homogeneous signal intensity but larger lesions can be nonhomogeneous.

Adult↗