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Biomedical subjects

A Rashid

Publications and source records attributed to A Rashid.

At least 91 records · Page 5Linked to original sources

Careers in academic general practice: problems, constraints, and opportunities.

Changing priorities in the NHS have underlined the crucial importance of academic general practice in providing quality training and research to underpin developments in general practice. Unfortunately, several problems and constraints mean that the full potential of general practitioners to make a contribution to teaching and research has not been realised. These issues are examined and recommendations for improvements are made. Obstacles to career development for academics in general practice should be removed. The funding of academic general practice should be the same as for other medical disciplines. Vocational training for general practice should be extended to include research and audit methods, particularly for doctors interested in an academic career. Above all, the long term objective should be to integrate undergraduate and post-graduate general practice to increase the overall effectiveness of teaching and research and hence the quality of service general practice.

Academic Medical Centers↗

Molecular mechanism of action of Pb2+ and Zn2+ on water oxidizing complex of photosystem II.

Pb2+ and Zn2+ inhibition of photosystem II (PSII) activity was reported to be mediated via displacement of native inorganic cofactors (Cl-, Ca2+ and Mn2+) from the oxygen evolving complex, OEC [Rashid and Popovic (1990) FEBS Lett. 271, 181-184; Rashid et al. (1991) Photosynth. Res. 30, 123-130]. Since the binding sites of these cofactors are protected by a shield of three extrinsic polypeptides (17, 23 and 33 kDa), we investigated whether these metal ions affect the extrinsic polypeptide shield of OEC. By immunoblotting with antibodies recognizing the 23 and 33 kDa polypeptides, we showed that both the metal ions significantly dissociated the 23 kDa (+17 kDa) polypeptide, and partially dissociated the 33 kDa. Ca2+, one of the important inorganic cofactors of oxygen evolution, strongly prevented the dissociating action of Pb2+ but did not prevent the action of Zn2+. The probable molecular mechanism of action of Pb2+ and Zn2+ on PSII OEC is discussed.

Lead↗

Involvement of granulocyte-macrophage colony-stimulating factor in pulmonary homeostasis.

The in vivo function of murine granulocyte-macrophage colony-stimulating factor (GM-CSF) was investigated in mice, carrying a null allele of the GM-CSF gene, that were generated by gene targeting techniques in embryonic stem cells. Although steady-state hematopoiesis was unimpaired in homozygous mutant animals, all animals developed the progressive accumulation of surfactant lipids and proteins in the alveolar space, the defining characteristic of the idiopathic human disorder pulmonary alveolar proteinosis. Extensive lymphoid hyperplasia associated with lung airways and blood vessels was also found, yet no infectious agents could be detected. These results demonstrate that GM-CSF is not an essential growth factor for basal hematopoiesis and reveal an unexpected, critical role for GM-CSF in pulmonary homeostasis.

Animals↗

A prospective randomised study of continuous warm versus intermittent cold blood cardioplegia for coronary artery surgery: preliminary report.

Between October 1991 and March 1993, 281 consecutive patients underwent non-emergency isolated coronary artery surgery under the care of one surgeon (A.R.). They were prospectively randomised to receive either intermittent cold (Group I-144 patients) or continuous warm (Group II-137 patients) blood cardioplegia for myocardial protection. There were no significant differences in clinical outcome between the two groups, as judged by operative mortality, rates of peri-operative myocardial infarction, blood loss, need for circulatory support, post-operative neurological deficit, or duration of intensive care or hospital stay. However, sinus rhythm returned spontaneously with greater frequency (91.2% vs 45.8%, P < 0.001) in Group II patients. There was greater transmyocardial oxidative stress in Group I patients, as evidenced by a significant rise in oxidised glutathione in coronary sinus blood on myocardial reperfusion. Also, the serum CKMb isoenzyme level 2 h post-operatively was significantly raised in Group I patients, although this difference had disappeared by the day after surgery. In conclusion this preliminary report suggests that continuous warm blood cardioplegia provides comparable myocardial protection to that achieved with standard hypothermic techniques in patients undergoing coronary artery surgery.

Coronary Angiography↗

Insights into stereochemical features of sulphated carbohydrates: X-ray crystallographic and modelling investigations.

The three-dimensional structures of the 2-, 3-, 4- and 6-monosulphates of methyl alpha-D-galactopyranoside have been determined by X-ray crystallography; the first two as the sodium salt, the third as both the sodium and potassium salts, and the fourth as a potassium salt. These represent the principal sulphated monomers of the carrageenan polysaccharides. The results extend our knowledge of the stereochemical features, such as ring conformation, sulphate geometry, hydrogen bonding and cation co-ordination, which characterize sulphated monosaccharides. The stereochemical data have been used to derive a mean geometry of the O-sulphate group and a set of force constants for use in molecular mechanics calculations on sulphated monosaccharides. These may be used in an extrapolation of the populations of stable conformers of related oligo- and polysaccharides.

Carbohydrate Conformation↗

Adherence of arthroconidia and germlings of anthropophilic and zoophilic varieties of Trichophyton mentagrophytes to human corneocytes as an early event in the pathogenesis of dermatophytosis.

The association (adherence) between human corneocytes and arthroconidia of Trichophyton mentagrophytes strains 121 and 126, and T. interdigitale strain 4 was studied in vitro. Adherence of arthroconidia to corneocytes from either the palm and sole occurred and increased with time up to 6 h, by which time germination of arthroconidia had started. Significant differences were seen between the T. mentagrophytes strains and T. interdigitale in their adherence to corneocytes from the palm. When adherence values for plantar corneocytes were compared, significant differences were found between T. mentagrophytes and T. interdigitale. Not all corneocytes from either site had adherent arthroconidia, although there was a time-dependent increase in the numbers of corneocytes with adherent fungal cells. By scanning and transmission electron microscopy it was seen that there was a loose association between arthroconidia and corneocytes with no apparent damage to the corneocyte membrane. Adherence of germlings of T. interdigitale to corneocytes from the palm appeared to be mediated by germling outer cell wall fibrils. Hyphal branches and secondary germlings were observed to enhance the attachment of the parent hypha to adjacent corneocytes.

Cell Adhesion↗

An audit of cardiac pacing in the elderly: effect of myocardial infarction on outcome.

OBJECTIVE: To audit the outcome of temporary endocardial pacing in an elderly population. DESIGN: Retrospective case-series analysis. SETTING: The Department of Medicine for the Elderly at the Wrexham Maelor Hospital, a District General Hospital with 612 beds serving a catchment population of 220,000. SUBJECTS: A sample of 50 consecutive elderly patients, with an age range of 65 to 99 years, undergoing transvenous cardiac pacing. MAIN OUTCOME MEASURES: Length of stay in hospital, complications of the pacing procedure, whether a permanent pacemaker was installed, and whether the patient died within 1 month of admission. RESULTS: There was no difference in length of stay between those with a myocardial infarction and those without. Minor complications occurred in three patients (one local infection and two "failures to pace"). Major complications occurred in two patients (septicemia and pneumonia). More patients without a myocardial infarction (86.9%) went on to implantation of a permanent pacemaker than those with an infarction (11.1%, P = 0.001), and fewer of them died (8.7% compared with 48.1%, P = 0.0025). In those patients with a myocardial infarction who died, there was no difference between the proportions who had inferior (7/18) and anterior (5/9) infarctions. CONCLUSION: Cardiac pacing seems to be a safe and reliable procedure in the elderly, although long term morbidity and mortality may be dependent on the presence or absence of myocardial ischaemic disease. Myocardial infarction in the elderly is an event of major significance, carrying with it a high mortality rate, particularly if accompanied by cardiogenic shock and the need for cardiac pacing.

Aged↗

Does the MRCGP examination discriminate against Asian doctors?

OBJECTIVE: To ascertain whether the membership examination for the Royal College of General Practitioners (MRCGP) discriminates against doctors of Indian subcontinent ethnic origin ("Asian doctors"). DESIGN: Retrospective analysis of data from five administrations of the MRCGP examination (December 1988-December 1990). SETTING: United Kingdom national examination body. SUBJECTS: 3686 doctors taking the examination for the first time, 244 of whom were classified as Asian, the remainder as non-Asian. MAIN OUTCOME MEASURES: Comparison of performance in each of the written and oral components of the examination between Asian doctors, identified by their names and classified into subgroups by countries of birth and primary medical training from data provided at registration, and non-Asian doctors. RESULTS: On written components of the examination (multiple choice paper mean score Asians versus non-Asians 42.3 v 48.6, modified essay paper 40.9 v 48.9, practice topic/critical reading paper 41.5 v 48.7, all p less than 0.001 by t testing). But analysis by countries of birth and primary training showed that these differences were due largely to poor performance by certain groups of Asian doctors, especially those born and trained in the Indian subcontinent or elsewhere outside the United Kingdom. Asian doctors born and trained in the United Kingdom and those born in Africa or the West Indies and trained in the United Kingdom performed similarly to the non-Asian doctors. CONCLUSIONS: The examination does not systematically discriminate against Asian doctors, but the poor performance of the two subgroups of Asians is cause for serious concern and requires investigation.

Asia↗

Comparison of GK1.5 and chimeric rat/mouse GK1.5 anti-CD4 antibodies for prolongation of skin allograft survival and suppression of alloantibody production in mice.

GK1.5 is a rat mAb that recognizes the mouse CD4 Ag. It has been shown to deplete CD4+ cells in vivo and to be immunosuppressive. To evaluate the effect of the C region of this antibody in achieving cell depletion, chimeric antibodies, each having the rat GK1.5 V regions and one of the four mouse IgG C region isotypes, were compared with the native rat antibody. The chimeric antibodies and the native antibody were tested for their ability to mediate in vitro C-dependent cytotoxicity, in vivo cell depletion, and prolongation of allogeneic skin graft survival and suppression of alloantibody production. In vitro C-dependent cytotoxicity assays revealed that rat IgG2b and the chimeric antibodies containing mouse IgG2a, mouse IgG2b, and mouse IgG3 were effective in lysing CD4+ lymphocytes whereas mouse IgG1 was ineffective. In vivo studies of CD4+ cell depletion showed that mouse IgG2a, rat IgG2b, and mouse IgG2b were effective isotypes, mouse IgG1 was less effective, and mouse IgG3 did not deplete CD4+ cells. A correlation was found between the ability of an isotype to deplete CD4+ cells in vivo and its ability to prolong the survival of skin allografts and to suppress alloantibody production. The nondepleting mouse IgG3 was ineffective in these assays. Overall the most effective mouse isotype was IgG2a which was as effective as rat IgG2b. These results indicate 1) that syngeneic isotypes of mAb can cause cell depletion and consequently the prolongation of allograft rejection and suppression of alloantibody production; 2) that not all isotypes are equally effective; and 3) that the ability of a given isotype to deplete cells in vivo does not correlate with its ability to mediate C-dependent lysis in vitro. Our results are consistent with the hypothesis that in vivo depletion of cells is mediated by opsonization and binding through the FcR.

Animals↗

Monte Carlo calculations of ion distributions surrounding the oligonucleotide d(ATATATATAT)2 in the B, A, and wrinkled D conformations.

We calculated the uni-univalent ion distributions around the oligonucleotide d(AT)5.d(AT)5 in the A, B and wrinkled D conformation using the Metropolis Monte Carlo method. All atoms were included in the oligonucleotide model with partial charges and hard sphere radii assigned to each atom. The univalent counter- and coions were modeled as hard spheres with radius 0.3 nm. The solvent was assigned a dielectric constant of 80, corresponding to a temperature of 298K. The counterion distribution surrounding each of the conformers and the distribution surrounding an impenetrable cylinder, were calculated for four salt concentrations. We found significant counterion density in the major groove of the A DNA while fewer counterions occupied the grooves of B DNA. In the wrinkled D DNA, where groove occupancy is sterically hindered, the ion distributions were identical to the distributions surrounding the impenetrable, cylindrical model. This suggests that excluded volume effects significantly influence the details of the ion distributions near the oligomer, while the detailed charge distributions of the oligomer affects the ion distributions only minimally. Although substantial variation in counterion density was observed near the oligomers of differing conformations, the total number of counterions located within a cylinder surrounding the oligomer bounded radially by 2.4 nm was independent of the conformation of the oligomer. Therefore, for this model system, the local univalent counterion distributions are extremely sensitive to the geometry of the oligonucleotide whereas the extent of neutralization of the oligoanion is insensitive to the conformation of the oligomer.

Base Sequence↗

Efficient and stereoselective synthesis of methyl 3-O-(3,6-anhydro-beta-D-galactopyranosyl)-alpha-D-galactopyranoside and methyl 3,6-anhydro-4-O-beta-D-galactopyranosyl-alpha-D-galactopyranoside.

Methyl 3-O-(3,6-anhydro-beta-D-galactopyranosyl)-alpha-D-galactopyranoside (3) and methyl 3,6-anhydro-4-O-beta-D-galactopyranosyl-alpha-D-galactopyranoside (4) have been synthesised stereoselectively using three coupling procedures. Acceptable yields were achieved using acetylated derivatives as donors and trimethylsilyl triflate as the catalyst. Intramolecular tosylate displacement to form 3,6-anhydro rings proceeded in methanolic sodium methoxide.

Carbohydrate Conformation↗

Simultaneous bilateral spontaneous pneumothorax: case report.

A 22-year-old previously healthy male was admitted to the emergency department for chest pain and dyspnea of 1-day's duration. He had a history of heavy smoking. The patient was cyanotic, agitated, and severely dyspneic. Lung auscultation revealed severe diffuse bronchospasm and equally diminished breath sounds on both sides. Nasotracheal intubation and mechanical ventilation were performed shortly after admission due to acute respiratory failure. Simultaneous bilateral spontaneous pneumothorax was diagnosed from the chest x-ray, and chest tube drainage was immediately performed bilaterally. Computerized tomography of the chest 1 month later showed diffuse emphysematous bullae of the lungs. The case presented here should increase physicians' awareness of this rare form of spontaneous pneumothorax and its diverse manifestations.

Adult↗

Normothermic arrest with continuous hyperkalaemic blood: initial experience.

The requirement for hypothermia in myocardial protection has recently been questioned. Between October 1990 and May 1991, diastolic arrest was achieved using continuous perfusion with normothermic, hyperkalaemic blood in 257 consecutive patients undergoing cardiac surgery. The mean age was 59.8 +/- 9.3 years (range 28-84 years). Coronary artery surgery was performed in 210 patients, valve replacements in 18, combined procedures in 22, and 7 patients had miscellaneous procedures. Eleven patients (4.3%) had undergone previous cardiac surgery, and 65 (25.3%) required urgent or emergency operations. Hyperkalaemic blood (7-20 mmol/l) was delivered antegradely in 190 (72.8%) patients (mean aortic root pressure 60-80 mmHg), retrogradely in 62 (25.3%) patients (mean coronary sinus pressure less than 40 mmHg), and by a combined route in 5 (1.9%). Sinus rhythm returned immediately after removal of the aortic clamp in 235 (91.4%) patients. Weaning from bypass was achieved without circulatory support in 207 (82.5%) patients. Of 233 patients undergoing non-emergency coronary artery surgery, single valve or combined procedures, 11 died, giving an operative mortality of 4.7%. Of 155 patients with good left ventricular function requiring coronary artery surgery, 3 (1.9%) died. The in-hospital mortality for the group as a whole was 7.3%. Sixteen (6.2%) patients sustained perioperative myocardial infarctions; of these 6 died. We conclude that continuous, normothermic, hyperkalaemic arrest is a simple and safe method of myocardial protection. It may avoid the damage associated with hypothermia, ischaemia and reperfusion.

Adult↗