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P Cook

Publications and source records attributed to P Cook.

136 records · Page 8Linked to original sources
PubMed1967

The effect of valinomycin on potassium and sodium permeability of HK and LK sheep red cells.

A cyclic depsipeptide antibiotic, valinomycin, was found to produce increased selective permeability of the plasma membranes of HK and LK sheep red blood cells to potassium but not to sodium ions. The compound had relatively little effect on the active extrusion of sodium from HK sheep red blood cells or on the Na + K-stimulated ATPase activity of membranes derived from these cells. It is proposed that the selective cation permeability produced by this compound depends primarily on steric factors, particularly the relationship between the diameter of the ring and the effective diameter of the ion. The significance of these results for the problem of the mechanism of ionic selectivity in natural membranes is discussed.

Adenosine Triphosphatases↗
PubMed1965

Separation of adenosine triphosphatase of HK and LK sheep red cell membranes by density gradient centrifugation.

Membrane fragments from high potassium (HK) and low potassium (LK) sheep red cells were separated by density gradient centrifugation. Three preparations were studied: (1) HK membranes sonicated for 20 minutes, (2) HK membranes sonicated for 3 minutes, and (3) LK membranes sonicated for 3 minutes. The adenosine triphosphatase (ATPase) activity in the maximally disrupted preparation (1) was not sensitive to Na + K and was recovered in relatively small but heavy (specific gravity 1.19) fragments which made up no more than 8 per cent of the total membrane. Both Na + K-sensitive (S) and Na + K-insensitive (I) ATPase activity were found in the more gently broken up preparations (2) and (3) but the ratio of S- to I-ATPase was much greater in HK than in LK membrane fragments. S-ATPase activity in preparation (2) was about 50 per cent that observed in HK membranes prior to sonication. S-ATPase activity was recovered from the density gradient in relatively large but light (specific gravity 1.10) fragments. As was the case with the maximally disrupted preparation (1), I-ATPase activity in both preparations (2) and (3) was recovered in small but heavy (specific gravity > 1.20) fragments. The possibility that sensitivity of sheep red cell membrane ATPase to Na + K depends on the association between units containing the enzyme(s) and large, light, phospholipid-containing components is discussed.

Adenosine Triphosphatases↗
PubMedDate not supplied

Monoclonal antibodies to E92, an endothelial cell surface antigen.

Two hybridoma-derived monoclonal antibodies have been developed that react with an antigen of molecular weight 92,000 daltons on the surface of human endothelial cells. Cultured human umbilical vein endothelial cells were used for immunization, but the antigen is present on arterial, venous and capillary endothelium, as determined by biotin-avidin immunoperoxidase staining of tissue sections. With this technique, other cell types in the tissues which were examined were not reactive, except for scattered fibroblasts and histiomonocytic cells, trophoblastic cells of the placenta, and benign immature mesenchymal cells in a renal cystadenocarcinoma. By cytofluorography, the antibodies were found to be unreactive with granulocytes, T lymphocytes, B lymphocytes, and the majority of monocytes. Fibroblasts were reactive with the antibodies, but the fluorescence tracings indicated a lower density of antigen on these cells than on endothelial cells. Immunoreactivity of fibroblasts could be decreased by treatment of the cells with thrombin, trypsin, or neuraminidase, whereas these enzymes did not affect the immunoreactivity of endothelial cells. The reactive antigen (E92) does not appear to be any of several previously described endothelial cell proteins, because of its molecular weight and its absence on other cell types. The presence of E92 on trophoblastic cells of the placenta and immature mesenchymal cells, as well as fibroblasts and endothelial cells, may indicate that it is a primitive antigen of mesodermal tissue that is lost by most cell types during differentiation.

Adenocarcinoma↗
PubMedDate not supplied

Kaposi's sarcoma in the Gambia, West Africa is less frequent in human immunodeficiency virus type 2 than in human immunodeficiency virus type 1 infection despite a high prevalence of human herpesvirus 8.

OBJECTIVES: To investigate the distribution of Kaposi's sarcoma (KS) cases in patients with human immunodeficiency virus types 1 and 2 (HIV-1 and HIV-2) infection in the Gambia; to document the prevalence of human herpesvirus 8 (HHV-8) infection in various population groups in the Gambia. STUDY DESIGN/METHODS: A retrospective analysis of KS cases in hospital records at the Medical Research Council (MRC) hospital was performed, along with a cross-sectional survey of HHV-8 prevalence in hospital-based and community-based study population with polymerase chain reaction (PCR) and serologic assays. RESULTS: After adjusting for gender and CD% at the first visit, HIV-1-positive patients were 12.4 times more likely to have KS than were HIV-2-positive patients. The prevalence of antibodies to HHV-8 and the HHV-8 genome was high in both HIV-1-positive and HIV-2-positive patients without KS. The prevalence of antibodies was also high in pregnant women who were HIV-1-positive, HIV-2-positive, or HIV-negative (73%, 83%, and 79%, respectively). CONCLUSIONS: HHV-8 infection is widespread in the Gambia. In addition to immunosuppression and HHV-8 infection, other cofactors specifically related to HIV-1 rather than HIV-2 appear to be involved in the development of KS.

AIDS-Related Opportunistic Infections↗
PubMedDate not supplied

[Minimizing the risks associated with QTc prolongation in people with schizophrenia. A consensus statement by the Cardiac Safety in Schizophrenia Group].

Schizophrenia is one of the most debilitating mental illnesses, complicated by an increased incidence of suicide amongst patients compared with the general population. A recent report has also demonstrated a 33% increase in -relative risk of death associated with circulatory disease, indicating that the latter may be a more critical factor than either suicide or accidental death in this population. Indeed, the average life expectancy of a person with schizophrenia is currently approximately a decade less than that of the general population. Additionally, it has been shown that in over 50% of people with schizophrenia, there is a reduction in their chance of reaching psychosocial goals. Since the arrival of the first antipsychotic drugs in the middle of the last century, the outlook for patients with schizophrenia has improved markedly. In particular, the introduction of the new generation (atypical) class of antipsychotic agents in the 1980s and 90s has resulted in a significant reduction in the incidence of violent and aggressive episodes in treated patients. A better side-effect profile of these drugs, especially reduced extra pyramidal symptoms (EPS), has resulted in improved patient outcomes and the possibility of good long-term control of the disorder. However, while the introduction of antipsychotic agents has undoubtedly revolutionised the prognosis for patients with schizophrenia, these medications are not without their own problems. One of the concerns to emerge over the last fifteen years is unpredictable, sudden and unexplained death in patients taking antipsychotic drugs. The cause of sudden death in this population is controversial and the role of drugs is not clear. People with schizophrenia also appear to be at higher risk of cardiovascular disease compared with the general population. Many factors may play a role in this including a higher prevalence of smoking, poorer diet, more sedentary lifestyle and a greater likelihood of alcoholism and substance abuse. However, it is possible that the impact of adverse effects on the cardiovascular system related to certain antipsychotic drug use may well increase the prevalence of mortality and morbidity due to cardiovascular events and may also play a significant role in the reduced life expectancy of the patient with schizophrenia. The range of mechanisms whereby antipsychotic drugs can influence cardiovascular function is very broad and includes: receptor blockade; conduction disturbance (eg bundle branch block); delayed ventricular repolarisation (prolonged QTc interval); left ventricular dysfunction; sinus node abnormalities; myocarditis; postural hypotension; polydipsia-hyponatremia syndrome; weight gain; glucose intolerance. Of these, QTc interval prolongation, with the risk of progression to the potentially fatal ventricular tachyarrhythmia Torsades de Pointes (TdP), is of particular concern as this arrhythmia is unpredictable and difficult to manage. Coupled with these clinical concerns are regulatory issues regarding several compounds that have received warnings or been withdrawn from the market. Recently, there has been no clear guidance for psychiatrists regarding QTc interval prolongation and TdP. This document seeks: 1) to explore drug-induced ventricular arrhythmias with particular emphasis on QTc interval prolongation as a warning of increased vulnerability, 2) to provide guidelines on the therapeutic management of the patient with schizophrenia to minimize the risk of iatrogenic cardiotoxicity. Several guidance documents have previously been published in this area including the report published by the UK Working Group of the Royal College of Psychiatrists' Psychopharmacology Sub-Group in 1997, and the policy document on the potential for QTc prolongation and proarrhythmia by non-antiarrhythmic drugs published in June 1999 under the auspices of the European Society of Cardiology. This document seeks to supplement currently published guidelines.

Antipsychotic Agents↗
PubMedDate not supplied

Diagnosis of low back pain: role of imaging studies.

The authors describe the benefits and limitations of standard radiography, bone scintigraphy, computed tomography, myelography, discography, and magnetic resonance imaging. They caution the physician to base decisions about obtaining imaging studies on whether the studies will influence patient management.

Diagnostic Imaging↗