Search PubMed⌕ Search

Biomedical subjects

C Clark

Publications and source records attributed to C Clark.

At least 163 records · Page 9Linked to original sources
PubMed1991

Association of human papillomavirus with penile carcinoma: a study using polymerase chain reaction and in situ hybridization.

Although carcinoma of the uterine cervix has been shown to be strongly associated with human papillomavirus (HPV) infection, a sexually transmitted disease, similar detailed data are lacking in penile carcinoma. To determine the association of HPV with penile carcinoma, we examined 30 specimens of penile carcinoma from 23 patients by the highly sensitive polymerase chain reaction (PCR) and in situ hybridization assays. We also examined nonneoplastic penile foreskins from 20 adults using the polymerase chain reaction assay. Human papillomavirus type 16 genome was found in 15 patients (65%), HPV type 30 was found in three (13%), and HPV type 6/11 was found in two (9%). These HPV types were not detected in any of the nonneoplastic foreskins. As in cervical carcinoma, HPV, particularly type 16, is strongly associated with penile carcinoma and may play an etiologic role in the development of this neoplasm.

Base Sequence↗
PubMed1991

Synergy between preactivated photofrin-II and tamoxifen in killing retrofibroma, pseudomyxoma and breast cancer cells.

Exposure of photoactive compounds to light prior to their use in biological systems (preactivation) results in the generation of tumour cell specific metastable cytotoxic species that are no longer dependent on the light energy. Thus, preactivation renders the photoactive compounds suitable for systemic use. We have examined the in vitro effect of preactivated photofrin-II and tamoxifen in retroperitoneal fibroma, pseudomyxoma and male breast carcinoma cell lines. These cells were found to be non-responsive to tamoxifen and were negative for oestrogen receptors. Incubation of these cells with 0.5 microgram/ml preactivated photofrin-II and tamoxifen (less than 10(-6) mol/l) resulted in a significantly enhanced (P less than 0.001) inhibition of DNA synthesis compared with either agent alone. This synergistic effect between tamoxifen and preactivated photofrin-II was determined by multiple drug effect analysis. Treatment of cells with preactivated photofrin-II did not cause the increased expression of oestrogen receptors. These observations suggest that a combination of antihormonal drugs with preactivated compounds may be of clinical value.

Breast Neoplasms↗
PubMed1991

Single photon emission computed tomography using 99mTc-HM-PAO in the routine evaluation of Alzheimer's disease.

Regional cerebral blood flow was studied in 7 patients with clinically suspected Alzheimer's disease and 10 normal controls by single photon computed emission tomography (SPECT) using HM-PAO. All patients with Alzheimer's disease and no controls had parietal lobe hypoperfusion which was usually bilateral. In patients with more severe dementia hypoperfusion extended into the frontal lobes. Parietal lobe hypoperfusion corresponds to parietal lobe degeneration which is the one of the first neocortical regions to show the typical degenerative changes of Alzheimer's disease. SPECT with HM-PAO is a non-invasive investigation available in most nuclear medicine departments and complements existing tests in the routine evaluation of patients presenting with dementia.

Aged↗
PubMed1991

Development of mock circulation models for the assessment of counterpulsation systems.

STUDY OBJECTIVE: This study entailed the development of mock circulation models to assess and compare the haemodynamic efficacy of extra-aortic counterpulsation (using trained skeletal muscle wrapped around the proximal descending aorta) and conventional intra-aortic balloon counterpulsation. DESIGN AND EXPERIMENTAL MATERIALS: Hydraulic Windkessel type lumped parameter models were used either in conjunction with native skeletal muscle or as a dynamic simulation of counterpulsation. The haemodynamic performance of the wrapped latissimus dorsi muscle of the normal sheep was assessed using an artificial load to simulate the pressurised proximal descending aorta. Mock circulation models of counterpulsation comprised Windkessel compliance chambers, laminar flow resistors, a blood analogue, a prosthetic blood pump, and a purpose made hydraulic counterpulsator. MEASUREMENTS AND MAIN RESULTS: An electrically stimulated muscle wrap, 5 cm in length, previously trained for 2 weeks at 3 V and 35 Hz, was assessed for haemodynamic performance in a mock circulation: volume of fluid displaced = 14.1(SD 1.8) ml; pressure increase from 100 mm Hg = 14.9(2.1) mm Hg; external work per contraction cycle = 180(70)mJ; external mean power = 800(100) mW. In a simulation of intra-aortic balloon counterpulsation, haemodynamic benefit (ie, an increase in proximal flow rate and endocardial viability ratio and a reduction in left ventricular stroke power) was assessed with respect to defined parameters. CONCLUSIONS: This paper demonstrates the potential of the mock circulation models both for the investigation of muscle wrap performance and for the comparison of extra-aortic muscle with intra-aortic balloon counterpulsation.

Counterpulsation↗
PubMed1991

Neuropsychological performance in patients with mild multiple sclerosis.

Although changes in cognitive function in patients with multiple sclerosis (MS) have been reported, these changes have been traditionally associated with the later stages of the disease. In the current study, a comprehensive neuropsychological battery was administered to MS patients (N = 86) in whom the disease progression was relatively mild and in remission and a demographically well-matched control group (N = 46). Besides the expected differences in tests of motor function, the two groups also differed on a number of cognitive tests with no motor demands. The two cognitive functions that appear impaired were learning and memory. Given that similar deficits have been found in MS patients with more severe symptoms, it is argued that changes in cognitive function can occur in the mild stages of the disease.

Adult↗
PubMed1991

Alveolar macrophage chemotaxis in fire victims with smoke inhalation and burns injury.

In vitro migration of alveolar macrophages was studied in 24 fire victims and 19 controls; all subjects were cigarette smokers. Unstimulated (P = 0.01) and stimulated migration towards casein-(P = 0.01) and zymosan-activated serum (P = 0.002) of macrophages from smoke inhalation patients (SI) (n = 19) was increased when compared to control subjects (CS). Migration of alveolar macrophages from patients with burns without smoke inhalation (burns only, BO) was not increased. Patients with smoke inhalation and no burns (smoke only, SO) (n = 9) had increased migration when compared to controls but this was not statistically significant. Patients with smoke inhalation and burns (SB) (n = 10) had increased unstimulated migration (P = 0.01) and increased migration towards casein (P less than 0.005), ZAS (P less than 0.002) and F-met-leu-phe (P less than 0.05) when compared to controls (CS). Lavage fluid from the fire victims displayed chemotactic activity towards normal human neutrophils and its analysis for the components of the complement cascade proved positive (Clq, Clr, Factor B and C3). These data suggest that activation of alveolar macrophages may contribute to the development of pathophysiological changes in patients with smoke inhalation (SI) and particularly those with smoke inhalation and burns (SB).

Burns↗
PubMed1991

Human cytomegalovirus inhibits human immunodeficiency virus replication in cells productively infected by both viruses.

We have been studying the role of human cytomegalovirus (HCMV) as a potential cofactor in human immunodeficiency virus (HIV)-related disease. The clinical relevance of HCMV is highlighted by the fact that it is a principal viral pathogen in patients with AIDS and is known to infect the same cells as HIV. In this study, we focused on the molecular interactions between HIV and HCMV in human fibroblasts and in the human glioblastoma/astrocytoma-derived cell line U373 MG, cells which can be productively infected by both viruses. Because these cells are CD4-, we used HIV pseudotyped with a murine amphotropic retrovirus as described previously (D. H. Spector, E. Wade, D. A. Wright, V. Koval, C. Clark, D. Jaquish, and S. A. Spector, J. Virol. 64:2298-2308, 1990). Initial studies showed that when cells were preinfected with HIV (Ampho-1B) for 5 days and then superinfected with HCMV, HIV antigen production dropped significantly in the coinfected cells but continued to rise in cells infected with HIV (Ampho-1B) alone. HCMV production, however, was unaffected by the presence of HIV. Further analysis showed that HIV steady-state RNA levels and gag and env protein production were also inhibited in the presence of HCMV. The transcriptional inhibition of HIV was particularly surprising in view of the previous results of several other laboratories as well as our own that HCMV infection stimulates HIV long terminal repeat-chloramphenicol acetyltransferase (LTR-CAT) expression in transient expression assays. To investigate this further, we transfected the HIV LTR-CAT construct into either uninfected cells or cells which had been preinfected with HIV. The cells were infected with HCMV 24 h posttransfection and assayed for CAT gene expression at 48 h after HCMV infection. Although there was some stimulation of the LTR-CAT in cells that were dually infected by HIV and HCMV, it was 16-fold less than that in the cells infected only with HCMV. This suggests that in the presence of the HIV infection, the stimulation of the HIV LTR-CAT gene by HCMV is significantly reduced. Experiments with UV-irradiated HCMV and the HCMV DNA polymerase inhibitor ganciclovir showed that HCMV transcription is necessary for the reduction in HIV production to occur; however, replication of the HCMV genome or any events which take place after DNA replication are not necessary. These results, coupled with the observation that inhibition is usually first seen between 8 and 24 h after HCMV infection, suggest that an HCMV early protein is involved in repression of HIV.

Antibodies, Monoclonal↗
PubMed1991

Characterization of in vivo expression of the human papillomavirus type 16 E4 protein in cervical biopsy tissues.

The role of human papillomavirus (HPV) proteins in the pathogenesis of cervical intra-epithelial neoplasia (CIN) and invasive cervical cancer is poorly understood. To characterize E4 protein expression in 49 paraffin-embedded cervical biopsies representing different histopathologic grades of disease, antibodies were elicited to a synthetic peptide corresponding to amino acids 20-34 of a protein predicted to be encoded by the HPV 16 E4 open reading frame. The E4 protein was detected throughout the spectrum of CIN, from CIN1 to CIN3. Expression was localized to the cell nucleus, primarily in the superficial layers of the squamous cervical epithelium. Ultrastructural studies showed that the E4 protein was organized into compact, intranuclear arrays 25-35 nm in diameter. E4 protein expression was also demonstrated in some histologically normal tissues containing HPV 16 DNA, but not in any of five cervical cancers containing HPV 16 DNA. These results suggest that E4 protein expression may precede development of light microscopic tissue abnormalities, that it may continue through the spectrum of CIN, and that expression of this protein may be reduced or terminated in invasive cancer. The function of this protein remains unknown, but its nuclear localization may be consistent with a role in viral maturation.

Amino Acid Sequence↗
PubMed1991

Regional metabolism in microsmic patients with schizophrenia.

The cerebral glucose metabolism of eight patients with schizophrenia and an olfactory agnosia was compared with that of eight normosmic patients with schizophrenia and eight normal controls. Since all patients were scanned while on their current medication regimen, the duration and dosage of the medication of the two patient groups were compared. Similarly, duration and dosage were correlated with absolute regional metabolic rates. No significant effects were found in these analyses. The patients with schizophrenia had significantly lower rates of frontal metabolism than the normal controls. However, the patients with schizophrenia and an olfactory agnosia had a lower right basal ganglia and thalamic metabolism than the normosmic patients with schizophrenia.

Adult↗
PubMed1990

Diversity of Conus neuropeptides.

Conus venoms contain a remarkable diversity of pharmacologically active small peptides. Their targets are ion channels and receptors in the neuromuscular system. The venom of Conus geographus contains high-affinity peptides that act on voltage-sensitive calcium channels, sodium channels, N-methyl-D-aspartate (NMDA) receptors, acetylcholine receptors, and vasopressin receptors; many more peptides with still uncharacterized receptor targets are present in this venom. It now seems that the Conus species (approximately 500 in number) will each use a distinctive assortment of peptides and that the pharmacological diversity in Conus venoms may be ultimately comparable to that of plant alkaloids or secondary metabolites of microorganisms. The cone snails may generate this diverse spectrum of venom peptides by a "fold-lock-cut" synthetic pathway. These peptides are specific enough to discriminate effectively between closely related receptor subtypes and can be used for structure-function correlations.

Amino Acid Sequence↗
PubMed1990

A model for teaching periodontal surgery.

A simple laboratory-made model is described for periodontal surgical technique exercises. It has proved useful for tutor demonstration and student practice of all aspects of flap management.

Humans↗
PubMed1990

Regional cerebral glucose metabolism in Turner syndrome.

Regional cerebral glucose metabolism was examined in females with Turner syndrome, a sex chromosome abnormality. Previous studies have found a visual/spatial cognitive anomaly in these women but, to date, no abnormalities in brain structure or function have been associated with the condition. In the present study, decreases in regional metabolism were found in the occipital and parietal cortex. The involvement of the occipital cortex, although consistent with the observed cognitive anomalies, has not been suggested previously as an area dysfunction. Because the occipital cortex is a primary sensory cortex, the reduction of glucose metabolism in the parietal cortex may reflect a lack of innervation from the occipital cortex. Besides insight into the functional specialization of the brain, these findings are also consistent with previous reports on animals regarding the effects of estrogen in brain maturation.

Adult↗
PubMed1990

Implications of olfactory agnosia for understanding sex differences in schizophrenia.

In our studies, 50 percent of the male patients with schizophrenia have an olfactory agnosia. This finding is of interest because the olfactory neuroanatomical network involves brain regions found to be abnormal in patients with schizophrenia, and this olfactory deficit appears to be sex dependent. This article reviews conceptual models for assessing olfactory function, describes the neuroanatomical structures involved, and reviews the findings of olfactory performance in patients with neurological dysfunction. The findings are then integrated with neuropathological studies of patients with schizophrenia. Finally, as there is increasing evidence for a sex difference in patients with schizophrenia, a model is suggested to account for these differences based on neuro-developmental and latent lesion hypotheses.

Agnosia↗
PubMed1990

Personality types of family practice residents in the 1980s.

This study was based on a nationwide sample of 778 family practice residents in the mid-1980s and was conducted to determine the personality types that were most common among those residents. The results showed that the single most common personality type was that in which the individual prefers to see the world in terms of challenges and future possibilities and to make decisions based upon his or her subjective values. These results showed that the sample differed significantly in Myers-Briggs personality type from both the general practitioners of the 1950s and the early family practice residents of the 1970s, who preferred to see the world in terms of the immediate facts of experience and to make decisions objectively. There were also significant differences between the civilian and military family practice residents, but not between the community-based and university-based residents. Implications regarding future practice styles, physicians' personal values, and manpower needs are discussed.

Career Choice↗
PubMed1990

Inhaled fentanyl as a method of analgesia.

A study was undertaken to investigate the use of fentanyl by aerosol for postoperative analgesia. Seven patients had placebo, six received fentanyl 100 micrograms and seven were given fentanyl 300 micrograms. A significant improvement in postoperative pain, as assessed by linear visual analogue scale, was achieved in the higher dose group, and in both fentanyl groups the time to alternative analgesia was significantly longer than in the control group. Serum fentanyl levels after inhalation of 100 micrograms reached a plateau around 0.04 ng/ml and after 300 micrograms at around 0.1 ng/ml after 15 minutes. Inhaled fentanyl may have a useful analgesic effect despite these low serum levels; this supports the hypothesis that the mode of analgesia from inhaled opioids may be different from that after other routes of administration. There were no adverse effects such as respiratory depression, bronchospasm, nausea or drowsiness.

Adolescent↗