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Biomedical subjects

G Clarke

Publications and source records attributed to G Clarke.

At least 37 records · Page 2Linked to original sources
PubMed2000

Rom-1 is required for rod photoreceptor viability and the regulation of disk morphogenesis.

The homologous membrane proteins Rom-1 and peripherin-2 are localized to the disk rims of photoreceptor outer segments (OSs), where they associate as tetramers and larger oligomers. Disk rims are thought to be critical for disk morphogenesis, OS renewal and the maintenance of OS structure, but the molecules which regulate these processes are unknown. Although peripherin-2 is known to be required for OS formation (because Prph2-/- mice do not form OSs; ref. 6), and mutations in RDS (the human homologue of Prph2) cause retinal degeneration, the relationship of Rom-1 to these processes is uncertain. Here we show that Rom1-/- mice form OSs in which peripherin-2 homotetramers are localized to the disk rims, indicating that peripherin-2 alone is sufficient for both disk and OS morphogenesis. The disks produced in Rom1-/- mice were large, rod OSs were highly disorganized (a phenotype which largely normalized with age) and rod photoreceptors died slowly by apoptosis. Furthermore, the maximal photoresponse of Rom1-/- rod photoreceptors was lower than that of controls. We conclude that Rom-1 is required for the regulation of disk morphogenesis and the viability of mammalian rod photoreceptors, and that mutations in human ROM1 may cause recessive photoreceptor degeneration.

Animals↗
PubMed2000

Mortality association of enhanced CD44v6 expression is not mediated through occult lymphatic spread in stage II colorectal cancer.

BACKGROUND AND AIMS: In the absence of other metastatic disease, the presence of lymph node metastasis remains the most important determinant of survival in colorectal cancer (CRC). Cluster designation 44 variant 6 (CD44v6) over-expression is associated with worse outcome in all stages of CRC. The CD44v6 is believed to confer metastatic potential through its facilitation of migration, extravasation and proliferation, although the specific means by which it conveys an adverse prognosis in CRC is unknown. The aim of the present study was to determine if CD44v6 over-expression in Stage II CRC subjects was associated with the presence of lymph node micrometastases. METHODS: We assessed tumour CD44v6 expression in 43 randomly sampled subjects who had resections for Stage II CRC between 1984 and 1991 by using immunohistochemistry. Micrometastases were sought in corresponding lymph node (LN) sections using keratin immunohistochemistry. RESULTS: There was a statistical trend between tumour CD44v6 over-expression and mortality (P = 0.09) and a significant relationship between LN cytokeratins and mortality (P = 0.01). There was no association between the detection of LN cytokeratins and tumour CD44v6 over-expression. CONCLUSION: We conclude that the adverse survival effect of CD44v6 over-expression is not mediated though lymphatic spread and postulate that it may therefore facilitate haematogenous metastasis.

Colorectal Neoplasms↗
PubMed2000

Modulation of synaptic transmission in the rat ventral septal area by the pharmacological activation of metabotropic glutamate receptors.

The ventral septal area (VSA) is considered to be critically involved in the control of the height and duration of fever. The major excitatory input to this region of the brain is glutamatergic, and the aim of this study was to investigate possible modulation of this synapse by metabotropic glutamate (mGlu) receptors. Whole-cell patch recordings were made from individual VSA neurons voltage-clamped at -60 mV. Activation of either group I or group II mGlu receptors (by bath application of 3,5-dihydroxyphenylglycine (DHPG) or (2S,2'R,3'R)-2-(2',3'-dicarboxycyclopropyl)glycine (DCG-IV), respectively) produced a long-lasting depression of synaptic transmission which in both cases was insensitive to the N-methyl-D-aspartate (NMDA) receptor antagonist D-2-amino-5-phosphonopentanoate (D-AP5). In contrast, application of (S)-2-amino-4-phosphonobutyric acid (L-AP4), a group III mGlu receptor agonist, had a biphasic effect on synaptic transmission in the VSA, first eliciting a transient depression of transmission during drug application, followed by a marked and sustained potentiation of synaptic transmission upon drug washout. The response elicited by L-AP4 was dependent on NMDA receptor activation, as in the presence of D-AP5 the potentiation was replaced by an underlying long-term depression (LTD) of transmission. These data provide the first evidence that metabotropic glutamate receptor agonists can induce both NMDA receptor-dependent and -independent modulation of synaptic transmission in the VSA.

2-Amino-5-phosphonovalerate↗
PubMed2000

The detection of cytokeratins in lymph nodes of Duke's B colorectal cancer subjects predicts a poor outcome.

OBJECTIVES: The objectives of this study were to examine the frequency of lymph node micrometastases detected by keratin immunohistochemistry and their relationship with survival behaviour. METHODS: A total of 133 consecutive patients staged as Duke's B, who had curative resection for colorectal cancer (CRC), comprised the study population. Patients who had died of a non-CRC-related cause or who became lost to follow-up were excluded, resulting in an amended population of 100. Study end-points were defined as disease-free survival of 5 years or CRC-related death. Paraffin-embedded lymph node sections were stained with a commercial cytokeratin antibody using a standard avidin-biotin technique. RESULTS: One quarter of subjects had micrometastases. Fifty-six per cent of subjects with positive lymph nodes had an adverse outcome, compared with 11% of subjects with negative nodes. A highly significant association was found between lymph node cytokeratin expression and mortality in both the univariate (log rank P = 0.0001) and multivariate (Cox proportional hazards P = 0.0123) analysis. CONCLUSIONS: Lymph node micrometastases detected by this inexpensive and simple technique are significantly associated with mortality in Duke's B CRC. This technique may be used to select patients for adjuvant chemotherapy.

Biomarkers, Tumor↗
PubMed2000

Recording wounds: Polaroid's new medically-designed cameras.

Wound management is an important and increasingly complex area of nursing practice. Community nurses, in particular, spend a considerable amount of time assessing, evaluating and managing chronic, non-healing wounds. The rapid rise in the number of wound care products, combined with the emphasis on clinical governance and risk management, and increases in litigation have meant that accurate documentation and record keeping have become an essential part of care (UKCC, 1992, 1998). A standardized approach to assessment, classification, measurement and evaluation should be adopted to maximize optimal patient outcomes. There are a number of techniques for measuring wounds, ranging from manual measurement using tracing to computer-based imaging. Photography is a simple and quick form of documentation, which provides an accurate and objective record of the wound. This article highlights the benefits of using the new Polaroid Macro 5 SLR camera in wound documentation.

Documentation↗
PubMed2000

Prostate cancer risk in relation to anthropometry and physical activity: the National Health and Nutrition Examination Survey I Epidemiological Follow-Up Study.

We studied the relationship of prostate cancer to anthropometry and self-reported physical activity among 5377 African-American and Caucasian participants in the National Health and Nutrition Examination Survey I cohort. The cohort was first examined between 1971 and 1975 and then followed prospectively through the Epidemiologic Follow-up Study in 1982-1984, 1986, 1987, and 1992. Men who reported low levels of nonrecreational physical activity had increased risk of prostate cancer compared with very active men. These findings were unchanged after adjustment for potential confounders and were stronger for African-Americans (relative risk, 3.7; 95% confidence interval, 1.7-8.4) than for Caucasians (relative risk, 1.7; confidence interval, 0.8-2.3). Lower levels of recreational activity were weakly associated with increased prostate cancer risk among African-Americans but not among Caucasians. Prostate cancer risk was unrelated to a variety of anthropometric variables. These results suggest that inactive men are at increased risk of prostate cancer.

Adult↗
PubMed1999

A three-array cochlear implant: a new approach for the ossified cochlea.

The ossified cochlea, although rare, represents a challenge for cochlear implantation. While it is no longer considered an absolute contra-indication to implantation, insertion may be technically difficult and the results may be suboptimal. Techniques which have been employed are reviewed. The new Digisonic multi-array implant, which was designed specifically for use in the ossified cochlea is described, along with the technique used for its insertion. In the first patient to be implanted with this new implant, all electrodes lie within the cochlea and are functional. The new Digisonic multi-array implant may have advantages over other solutions for the ossified cochlea.

Adult↗
PubMed1999

Comparing practice patterns of consumer and non-consumer mental health service providers.

The practice patterns of consumer and non-consumer providers of assertive community treatment are compared using both quantitative and qualitative data collected as part of a randomized trial. Activity log data showed that there were few substantive differences in the pattern of either the administrative or direct service tasks performed by the two teams. In contrast, the qualitative data revealed that there were discernable differences in the "culture" of the two teams. The consumer team "culture" emphasized "being there" with the client while the non-consumer team was more concerned with accomplishing tasks.

Case Management↗
PubMed1999

The effect of aprotinin on interleukin-8 concentration and leukocyte adhesion molecule expression in an isolated cardiopulmonary bypass system.

We examined the effect of aprotinin on the production of interleukin-8 and the expression of leukocyte adhesion molecules in an isolated cardiopulmonary bypass circuit. Five healthy volunteers each donated 500 ml blood which was divided into equal portions (A) and (B). Portion A was treated with aprotinin 250000 kallikrein inactivator units and added to a circuit primed with a further 250000 kallikrein inactivator units. Portion B was simultaneously treated with 25 ml normal saline and added to an aprotinin-free circuit. Samples of blood were taken at donation, after addition of a drug and at 30-min intervals throughout isolated cardiopulmonary bypass. The interleukin-8 increase was smaller in the aprotinin group but the difference between groups was not statistically significant (p > 0.05). In contrast, aprotinin inhibited the cardiopulmonary bypass-induced increase in monocyte (p < 0.05) and granulocyte (p < 0.01) CD18 and the increase in granulocyte, but not monocyte, CD11b (p < 0.05). Cardiopulmonary bypass had little effect on expression of L-selectin. These results confirm that aprotinin attenuates leukocyte activation during isolated cardiopulmonary bypass.

Aprotinin↗
PubMed1999

Immunohistochemical detection of mutant p53 protein in regional lymph nodes is associated with adverse outcome in stage II colorectal cancer.

Epidemiologic data identifies a cohort of Duke's B (CRC) patients whose survival more closely matches that of Duke's C. Lymph node micrometastases may account for this discrepancy. Lymph node expression of mutant p53 protein (Mp53P) has been linked to a reduction in survival in Japanese Duke's B patients. We aimed to determine the significance of nodal p53 expression in European Duke's B patients using immunohistochemistry. The study comprised 134 consecutive patients who had resections for CRC between 1984 and 1991. End points were 5 year disease free survival or CRC related death. Thirty-four subjects did not achieve end points and were excluded. We examined tumour and nodal sections for Mp53P by immunohistochemistry and correlated this with survival using a Kaplan-Meier (KM) and a Cox Proportional hazards model (CPHT). Five year survival was 73%. Fifty-eight percent of primary tumours expressed Mp53P. Tumour p53 expression did modulate survival behavior. Twenty-six percent of subjects' lymph nodes expressed Mp53P. Fifty-three per cent of those with positive and 17% of those with negative lymph nodes died of recurrence. The relative risk for nodal Mp53P expression was 3.1. There was a significant univariate relationship between lymph node p53 expression and mortality. (Log Rank p = 0.028). Multivariate analysis also showed a significant relationship with mortality. (CPHT p = .03). We conclude that lymph node expression of Mp53P is associated with increased mortality in Duke's B CRC.

Adult↗