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Biomedical subjects

K Whittaker

Publications and source records attributed to K Whittaker.

17 recordsLinked to original sources
PubMed2000

Drosophila p53 is a structural and functional homolog of the tumor suppressor p53.

The importance of p53 in carcinogenesis stems from its central role in inducing cell cycle arrest or apoptosis in response to cellular stresses. We have identified a Drosophila homolog of p53 ("Dmp53"). Like mammalian p53, Dmp53 binds specifically to human p53 binding sites, and overexpression of Dmp53 induces apoptosis. Importantly, inhibition of Dmp53 function renders cells resistant to X ray-induced apoptosis, suggesting that Dmp53 is required for the apoptotic response to DNA damage. Unlike mammalian p53, Dmp53 appears unable to induce a G1 cell cycle block when overexpressed, and inhibition of Dmp53 activity does not affect X ray-induced cell cycle arrest. These data reveal an ancestral proapoptotic function for p53 and identify Drosophila as an ideal model system for elucidating the p53 apoptotic pathway(s) induced by DNA damage.

Amino Acid Sequence↗
PubMed1999

Facilitating learning in the community with lecturer-practitioner posts.

The purpose of this paper is to present a case study of the perspectives of their role of a group of community lecturer-practitioners and a community teacher, who referred to themselves as 'community facilitators'. A qualitative design was used and data were collected by semi-structured interviews. These were transcribed and content analysis was undertaken. All participants provided a liaison role between the college and the community practitioners, prepared students for their clinical experience and assisted in relating theory to practice. The participants described how they managed the role and how they supported each other. Developing small teams of facilitators may provide a bridge between teachers and practitioners and can serve as a basis for further study of the lecturer-practitioner role.

Adult↗
PubMed1999

Continuing education needs of community nurses, midwives and health visitors for supervising and assessing students.

The objective of this study was to ascertain the changing educational needs of community nurses, midwives and health visitors in relation to the teaching, supervising and assessing of pre- and post-registration students. A questionnaire was sent to all education institutions providing community nursing experience in England (Whittaker et al. 1997), which allowed identification of three centres for in-depth study. Questionnaires were sent to practitioners (community nurses and midwives, health visitors and school nurses), their managers, and teachers of community courses in the three centres: 314 were returned. Eight semi-structured interviews were undertaken with volunteers in each of the study centres (n = 24). Extensive demands are being made on community staff to provide learning experiences for students on a wide range of courses. Practitioners reported that in order to fulfil their teaching and assessing functions they needed continuing education in matters which would assist them to provide research-based practice and education, teaching and assessing in the community and personal skills, for example assertiveness and counselling. Less than a quarter of practitioners were undertaking continuing education courses. However, opportunities for further academic study varied enormously and most practitioners had to study in their own time at their own expense.

Clinical Competence↗
PubMed1996

Experimental microneurosurgery of the trigeminal nerve: surgical technique for ganglionectomy and rhizotomy in the cat.

The techniques of two experimental surgical operations on the trigeminal nerve are described, namely, excision of the trigeminal ganglion (ganglionectomy) and division of the trigeminal root (rhizotomy), in the cat. These techniques have been developed with the specific aims of achieving the trigeminal lesion and also preserving a satisfactory postoperative quality of life for the animal in order to make it possible to study the long-term effects of trigeminal dennervation. To the best of our knowledge, a detailed description of such a surgical methodology is lacking; reporting of these procedures may facilitate future research on the trigeminal nerve.

Animals↗
PubMed1996

Perfluorochemical oxygen carriers: potential uses in neurosciences.

In this article we review recent developments in the field of "first-" and "second-generation" perfluorochemical (PFC) oxygen carriers. Particular emphasis is placed on the latest research and its implications regarding the clinical and experimental neurosciences. These compounds are ideally suited to the transportation of O2 within the vascular system. Two properties that facilitate their use in this respect are their very high solubility coefficients for O2 and CO2 and their biological inertness. Unfortunately, their widespread use has been limited by logistical difficulties associated particularly with their molecular behavior in vivo. However, advances in PFC technology have led to renewed interest. A potential role for second-generation PFCs in cerebral protection is exciting. Other possible significant applications are slowly becoming established in clinical practice. Currently under investigation are potential uses in the management of severe head injuries, radiotherapy or chemotherapy of malignant brain tumors, protection against air embolism, preservation of organs for transplantation, and as a tool in microsurgery of the retina or other parts of the CNS. Diagnostic neuroimaging applications could include the employment of PFCs as adjuncts in ultrasound, Doppler, computed tomography (CT), and magnetic resonance (MR) to achieve enhanced imaging and precise staging of inflammatory, neoplastic, and vascular disease processes. Research applications could include their use in magnetic resonance imaging and spectroscopy in assessing cerebral blood flow, local oxygen tension, and brain metabolism, in molecule-specific imaging, and as physiological markers of O2, ions, and pH.

Animals↗
PubMed1995

Morphometry of small airways in smokers and its relationship to emphysema type and hyperresponsiveness.

Based on our previous finding, of increased small airways disease in centrilobular emphysema (CLE) when compared with panlobular emphysema (PLE), we hypothesized that smokers who develop CLE would have increased airway responsiveness associated with airway inflammation and exaggerated airway narrowing, but not smokers with PLE. We compared preoperative methacholine challenge with the morphologic and cellular inflammatory characteristics of the airways in the lungs of six nonsmokers, 10 smokers with CLE, and five smokers with PLE. The airways of the CLE group were narrower than those of the nonsmokers (KS < 0.05) and the PLE group (KS < 0.05), but perimeters were not different. A greater percentage of airways in the CLE group showed infolding of the epithelium and lumen deformity than in the PLE group and nonsmokers (p < 0.05). Airway inner wall thickening (WI) was increased in the CLE group when compared with the PLE group and nonsmokers (p < 0.05), and WI correlated significantly with PC20 in the CLE group (r = -0.64, p < 0.01) but not in the PLE group and nonsmokers. The number of T lymphocytes in the airway walls correlated with PC20 in the CLE group (r = -0.50, p < 0.05) but not in the PLE group. In conclusion, despite similar age, smoking history, and range of airflow limitation, there was a clear difference in the methacholine responsiveness between the emphysema groups, suggesting that responsiveness is not just a reaction to smoking but either a reaction developing in some smokers or an abnormality initially present in some smokers which, in combination with exposure to cigarettes, determines the development of a type of lung disease: CLE.

Aged↗
PubMed1993

Domains of E1A that bind p105Rb, p130, and p300 are required to block nerve growth factor-induced neurite growth in PC12 cells.

Nerve growth factor (NGF) causes PC12 cells to cease division and undergo sympathetic neuron-like differentiation, including neurite outgrowth. We have tested whether differentiation and division share overlapping control mechanisms in these cells. To do this, we have perturbed the activity of proteins known to participate in cell-cycle regulation by introducing the E1A oncogene or its mutant forms via microinjection into PC12 cells. The E1A protein binds to several putative cell cycle control proteins, including p105Rb (the product of the retinoblastoma susceptibility gene), as well as others of unknown function such as p130, p107, and p300. Similar to previous results, we find that wild-type E1A abrogates NGF-induced neurite extension. However, NGF does cause neurite outgrowth in the presence of E1A mutants known to have greatly reduced binding to either p105Rb and p130 or p300. Our experiments suggest that p105Rb, p130, and p300 may participate either in E1A-mediated inhibition of differentiation or in the NGF signal transduction pathway. We also report here that NGF affects phosphorylation of p105Rb, suggesting that Rb mediates at least some of NGF's effects. Our results raise the possibility that putative cell-cycle control proteins may participate not only in NGF-induced cessation of division but also in differentiation.

Adenovirus E1A Proteins↗
PubMed1989

Fumarate reductase mutants of Escherichia coli that lack covalently bound flavin.

Menaquinol-fumarate oxidoreductase of Escherichia coli is a four-subunit membrane-bound complex that catalyzes the final step in anaerobic respiration when fumarate is the terminal electron acceptor. The catalytic domain of fumarate reductase consists of the FrdA subunit, which contains the active site, and a FAD prosthetic group covalently attached to His44, plus the FrdB subunit which contains at least two of the three nonidentical iron-sulfur clusters of the enzyme. To examine the role of covalently bound FAD in enzyme activity and electron transfer during anaerobic cell growth, site-directed mutagenesis was used to alter His44 of the FrdA subunit to a Ser, Cys, or Tyr residue. The resulting mutant enzyme complexes that were synthesized associated normally with the cytoplasmic membrane, but had decreased ability (greater than 70%) to reduce fumarate with reduced benzyl viologen, an artificial electron donor of low redox potential (Em = -359 mV; Clark, W. M. (1972) Oxidation-Reduction Potentials of Organic Systems, Robert E. Kreiger Publishing Co., Melbourne, FL). Even lower activities were measured when the higher potential, natural electron donor menaquinol was used, which, however, correlated with the slower growth rates of the different mutant complexes. In contrast to the normal enzyme, the mutant enzyme complexes were unable to oxidize succinate. Substitution of Arg for His44 produced a totally inactive enzyme complex that permitted no cell growth on nonfermentable substrates with fumarate as electron acceptor. All four mutant complexes contained noncovalently bound FAD in stoichiometric amounts. These data indicate a unique role of the 8 alpha-[N(3)-histidyl] FAD linkage in enzyme activity, by raising the redox potential of free FAD to permit reduction by both menaquinol and succinate.

Amino Acid Sequence↗
PubMed1988

Subunit location of the iron-sulfur clusters in fumarate reductase from Escherichia coli.

The subunit location of the [2Fe-2S], [3Fe-4S], and [4Fe-4S] clusters in Escherichia coli fumarate reductase has been investigated by EPR studies of whole cells or whole cells extracts of a fumarate reductase deletion mutant with plasmid amplified expression of discrete fumarate reductase subunits or groups of subunits. The results indicate that both the [2Fe-2S] and [3Fe-4S] clusters are located entirely in the iron-sulfur protein subunit. Information concerning the specific cysteine residues that ligate these clusters has been obtained by investigating the EPR characteristics of cells of the deletion mutant amplified with a plasmid coding for the flavoprotein subunit and a truncated iron-sulfur protein subunit. While the results are not definitive with respect to the location of the [4Fe-4S] cluster, they are most readily interpreted in terms of this cluster being entirely in the flavoprotein subunit or bridging between the two catalytic domain subunits. These new results are discussed in light of the amino acid sequences of the two subunits and the sequences of structurally well characterized iron-sulfur proteins containing [2Fe-2S], [3Fe-4S], and [4Fe-4S] centers.

Amino Acid Sequence↗
PubMed1988

Myelodysplastic syndrome in a kindred with ins(16) (p11.2).

A constitutional karyotypic abnormality, ins(16)(p11.2), is described in a case of myelodysplastic syndrome (MDS). The source of material for this insertion could not be established, but did not arise from either a balanced deletion or translocation, and did not consist of constitutive heterochromatin as defined by C-banding. The same lesion was found in both sisters, both nephews and four of the five great-nephews. Of these, all were phenotypically and haematologically normal, with the exception of a great-nephew who at the age at the age of 6 exhibits features compatible with partial trisomy 16p. The relationship of the karyotypic abnormality to the MDS and partial trisomy 16p in this family is discussed.

Blood Cell Count↗
PubMed1988

Secondary prevention in elderly survivors of heart attacks.

More than 200,000 elderly patients survive myocardial infarctions each year. Thus, the achievement of even minimal decreases in reinfarction and mortality rates will benefit large numbers of patients. Secondary prevention strategies include smoking cessation; the control of hyperlipidemia, obesity and diabetes; the management of hypertension and stress; exercise; the use of drugs such as beta blockers and aspirin, and increased attention to general health.

Adrenergic beta-Antagonists↗
PubMed1986

Prognostic importance of hypodiploid hemopoietic precursors in myelodysplastic syndromes.

It has been suggested that a poor prognosis and the development of leukemia in patients with myelodysplasia may be related to chromosomal abnormalities. We measured the DNA content of bone marrow cells with flow cytometry in 19 hematologically normal subjects and in 70 patients who had recently been diagnosed as having myelodysplasia. Thirty-four of the patients were found to have aneuploidy. This was not related to the percentage of blast cells in the bone marrow, and there was no demarcation in terms of DNA content between patients with a high percentage of blast cells and those with a low percentage of such cells. Patients with hypodiploid marrow cells had a significantly shorter survival time than other patients (P = 0.001). Patients with hyperdiploid marrow and those whose marrow had a normal DNA content had similar survival times. Hypodiploidy appears to be a better indicator of poor survival than the marrow blast-cell count. Patients with sideroblastic anemia invariably had cells with a normal or high DNA content; none of these patients died during the study. Our data suggest that there is a relation between the loss of chromosomal material and progression toward a leukemic phenotype. It is tempting to speculate that this process may involve a loss of negative regulatory genes ("anti-oncogenes").

Aneuploidy↗
PubMed1980

The effect of timolol vs placebo on angina pectoris.

The effect of timolol vs placebo on the frequency of anginal episodes, nitroglycerin consumption and exercise performance was investigated in a double-blind, randomized, crossover study in 23 patients with angina pectoris. The optimal dose of timolol (10-30 mg twice daily) for each patient was titrated by exercise studies. Compared with placebo, timolol decreased the weekly number of anginal attacks and the weekly number of nitroglycerin tablets consumed, reduced the resting heart rate, systolic and diastolic blood pressure, and product of systolic blood pressure times heart rate, decreased the heart rate, systolic and diastolic blood pressure, and product of systolic blood pressure times heart rate at the onset of angina pectoris or marked fatigue, prolonged exercise duration, and diminished electrocardiographic evidence of myocardial ischemia. Timolol is an excellent antianginal agent when prescribed twice daily, with the optimal dose titrated by exercise studies.

Angina Pectoris↗
PubMed1979

Acebutolol in supraventricular arrhythmias.

The effect of intravenous acebutolol on supraventricular arrhythmias was evaluated in 20 patients, 5 with chronic obstructive pulmonary disease. A rapid ventricular rate in atrial fibrillation was slowed greater than 15% in all of 10 patients by acebutolol and in none of 5 patients by saline. A rapid ventricular rate in atrial flutter was slowed greater than 15% in all of 6 patients by acebutolol and in none of 3 patients by saline. Frequent premature atrial beats were abolished or reduced by greater than 75% in each of 2 patients by acebutolol and not in a patient by saline. Acebutolol converted multifocal atrial tachycardia to sinus rhythm in a patient. Digitalis-induced nonparoxysmal atrioventricular junctional tachycardia was not affected by saline but was abolished by acebutolol in a patient. Acebutolol was well tolerated in each of 5 patients with chronic obstructive pulmonary disease. Acebutolol is useful in the treatment of supraventricular arrhythmias.

Acebutolol↗
PubMed1979

Treatment of premature ventricular complexes with acebutolol.

The effect of intravenous acebutolol versus saline solution on frequent premature ventricular complexes was evaluated in a double-blind, randomized study in 20 patients, including 3 with chronic obstructive pulmonary disease. Frequent premature ventricular complexes were abolished or reduced by 75% or more in none of 12 patients given saline solution but in 18 of 20 patients (90%) given acebutolol (P less than 0.001). This therapeutic effect of acebutolol persisted for at least 2.5 hours in 17 of 20 patients (85%), for at least 3.5 hours in 14 (70%) and for at least 4 hours in 8 (40%). Acebutolol was well tolerated by the three patients with chronic obstructive pulmonary disease. These data indicate that intravenous acebutolol is useful in the treatment of premature ventricular complexes.

Acebutolol↗
PubMed1979

Effect of prazosin vs placebo on chronic left ventricular heart failure.

The effect of the vasodilator prazosin vs placebo on exercise duration until marked dyspnea, and on left ventricular function measured by echocardiography, was evaluated in a double-blind, randomized study in 24 patients with chronic left ventricular failure despite digitalis and diuretic therapy. Compared with the double-blind placebo, prazosin reduced resting systolic and diastolic blood pressure and systolic blood pressure times heart rate, improved clinical symptoms, decreased cardiothoracic ratio measured by chest roentgenography, decreased left ventricular and left atrial dimensions, improved ejection fraction and Vcf measured by echocardiography, and improved treadmill exercise duration. All 12 patients taking prazosin had greater than or equal to 20% improved treadmill exercise duration; none of 12 receiving placebo improved. In six of 12 patients taking prazosin, roentgenographic evidence of pulmonary venous congestion disappeared compared with none of the patients on placebo. These data suggest that prazosin may be effective in treating chronic left ventricular failure.

Adult↗