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Biomedical subjects

A Baines

Publications and source records attributed to A Baines.

8 recordsLinked to original sources
PubMed1999

Leukocyte-endothelial cell interactions in nitric oxide synthase-deficient mice.

Nitric oxide (NO) is known to be an important endogenous modulator of leukocyte-endothelial cell interactions within the microcirculation. We examined leukocyte rolling and adhesion under baseline conditions and following thrombin (0.25 U/ml) superfusion in the mesentery of wild-type, inducible NOS (iNOS)-deficient (-/-), neuronal NOS (nNOS) -/-, and endothelial cell NOS (ecNOS) -/- mice to further our understanding of NO and leukocyte function. Baseline leukocyte rolling (cells/min) was significantly elevated in both the nNOS -/- (30.0 +/- 4.0) and ecNOS -/- mice (67.0 +/- 12.0) compared with wild-type mice (11.0 +/- 1.4). In addition, baseline leukocyte adherence (cells/100 micrometers of vessel) was also significantly elevated in the nNOS -/- (5.2 +/- 1.0) and ecNOS -/- (13.0 +/- 1.3) compared with wild-type animals (1.3 +/- 0.5). Deficiency of iNOS had no effect on baseline leukocyte rolling or adhesion in the mesentery. Baseline surface expression of P-selectin was observed in 68.0 +/- 9.0% of intestinal venules in ecNOS -/- mice compared with 10.0 +/- 2.0% in wild-type mice. Additional studies demonstrated that administration of an anti-P-selectin monoclonal antibody (RB40. 34) or the soluble P-selectin ligand, PSGL-1, completely inhibited the increased rolling and firm adhesion response in nNOS -/- and ecNOS -/- mice. Transmigration of neutrophils into the peritoneum following thioglycollate injection was also significantly augmented in nNOS -/- and ecNOS -/- mice. These studies clearly indicate the NO derived from both nNOS and ecNOS is critical in the regulation of leukocyte-endothelial cell interactions.

Animals↗
PubMed1995

Alterations in chemically induced tissue injury related to all-trans-retinol pretreatment in rodents.

Retinol (vitamin A) is an essential nutrient which has many physiological effects throughout the body. Our studies have demonstrated that retinol modulation of immune response, through alteration of macrophage and neutrophil function, can have dramatic effects on the toxicity of some compounds. Based on these studies, our current hypothesis for retinol potentiation of chemical-induced liver injury is that retinol administered to rats prior to the hepatotoxicant (CCl4 and AA in rats; and AA, APAP, and GalN in mice) primes the Kupffer cells to a more active state. This may occur in part as a result of increases in chemical mediators such as TNF from these Kupffer cells. Following hepatocyte damage by a toxicant, Kupffer cells are activated to release reactive oxygen species, immune mediators, and chemotactic factors which all serve to enhance the inflammatory response. This increased inflammatory response then results in increased injury to the already toxicant-damaged hepatocytes. In addition, retinol modulation of toxicant activation and detoxification may also make important contributions to the potentiation of some toxicants such as AA. Retinol protection of CCl4 hepatotoxicity in mice is more difficult to explain at this time but is possibly related to alterations in CCl4 metabolism in this species. Differences in response between pulmonary and liver macrophages (Kupffer cells) may explain the retinol protection from 1-NN pulmonary toxicity. Retinol may decrease the inflammatory response through downregulation of pulmonary macrophage function, thus resulting in decreased pulmonary injury. Finally, since retinol protection of cadmium toxicity in the liver and testis requires 7 days of retinol pretreatment, we suspect that retinol is inducing protective protein(s) in these organs. Aside from its normal biological role in rhe body, clinical medicine has found new uses for retinol in the treatment and prevention of some cancers, and in the treatment of certain dermatologic conditions. Since these patients are frequently administered or exposed to other potentially toxic compounds, it is obviously prudent and necessary to continue research into the effects of retinol on immune modulation and interaction with other compounds. More importantly, these studies demonstrate the modulation of immune function is one mechanism by which one chemical can influence the toxicity of another.

Animals↗
PubMed1994

Which cervical sampler? A comparison of four methods.

Four cytology sampling methods were compared in 1063 patients referred for colposcopy with a recent abnormal smear. A dyskaryotic smear of any grade was considered a positive result, though comparisons were limited to cases with a subsequent biopsy confirming CINII or III. There were no differences between the abilities of any of the four methods to detect higher grades of CIN (chi (2)3 = 4.603, P > 0.20). The presence or absence of endocervical cells in a smear was not significantly associated with any variation in success rate (chi (2)1 = 0.959, P > 0.30). The joint analysis of the four methods and the presence/absence of endocervical cells also showed no significant effects (chi (2)7 = 12.768, 0.1 > P > 0.05). In the latter analysis the trend towards a conventional level of significance was accounted for by the Aylesbury spatula giving a relatively high success rate when endocervical cells were present. The suggestion of advantage for the Aylesbury spatula merits further investigation.

Cervix Uteri↗
PubMed1993

Extrarenal effect of cyclosporine A on potassium homeostasis in renal transplant recipients.

Cyclosporine A (CyA) is known to cause hyperkalemia by impairing renal potassium excretion. However, the observation of transient and severe hyperkalemia occurring within 3 to 5 hours of CyA ingestion in several organ transplant patients led us to postulate that it might also cause a potassium efflux from the intracellular to the extracellular fluid space. We tested this hypothesis by studying 22 nondiabetic, renal transplant patients with stable renal function (serum creatine < 2.25 mg/dL) who were treated with CyA (CyA group; n = 14) or imuran and prednisone (STD group; n = 8). Eight CyA and four STD patients also were treated with a beta-blocker (BB). While at rest, fasting plasma potassium levels were sampled hourly in all patients from 8:00 am to 1:00 pm. All medications (including CyA and BBs) were given after the 8:00 am blood sampling. Venous pH, osmolality, insulin, aldosterone, epinephrine, norepinephrine, and CyA levels also were determined at 8:00 am, 11:00 am, and 1:00 pm. Urine was collected from 11:00 pm to 8:00 am prior to the study (period I) and from 8:00 am to 1:00 pm during the study (period II) for measurement of potassium excretion (standardized to a 5-hour period). A significant increase in serial plasma potassium levels was noted in the CyA + BB group only (P = 0.0006 by repeated measures analysis of variance).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Effect of using protocols on medical care: randomised trial of three methods of taking an antenatal history.

OBJECTIVE: To compare the effectiveness of three methods of taking an antenatal history on the quality of obstetric care. DESIGN: Randomised controlled trial. SETTING: Antenatal clinic of St James's University Hospital, Leeds. SUBJECTS: 2424 women attending the hospital for the first (booking) visit. INTERVENTIONS: Histories were taken by midwives using an unstructured paper questionnaire, a structured paper questionnaire (incorporating a checklist), or an interactive computerised questionnaire (incorporating 101 clinical reminders). MAIN OUTCOME MEASURES: The number of clinical responses to factors arising from the antenatal booking history according to method of taking the history. Actions were categorised as medical and surgical, obstetric, personal, current symptoms and treatment, related to maternal age, and related to two common actions (cervical smear testing and dental hygiene) and were weighted for clinical importance by 10 obstetricians. RESULTS: Overall the unstructured questionnaire generated 1063 actions, the structured questionnaire 1146, and the computerised questionnaire 1122. The clinical importance of these actions was lowest for the unstructured questionnaire (overall total value score 1987 v 2182 and 2110 for the structured and computerised questionnaires respectively). The structured questionnaire was better than the computerised questionnaire in the medical and surgical (total value score 191 v 184), obstetric (275 v 241), and personal (430 v 360) categories but inferior in the current symptoms category (179 v 191). CONCLUSION: Structured questionnaires (computerised or paper) provide more and better information, and their use improves clinical response to risk factors. Computerised systems offer no further advantage in antenatal clinics.

Clinical Protocols↗
PubMed1987

Synapsin I: a regulated synaptic vesicle organizing protein.

Synapsin is a protein initially discovered and characterized as a target for cyclic AMP and Ca/calmodulin-regulated protein kinases that is concentrated in nerve endings and is localized on the surface of small synaptic vesicles. Synapsin shares antigenic sites and some local regions of homology with erythrocyte protein 4.1, although these proteins in general are quite different in sequence. Protein 4.1 and synapsin share several local regions of homology with erythrocyte spectrin alpha subunit. Protein 4.1 and synapsin may be related to each other through a common relationship with spectrin. Synapsin binds to synaptic vesicles and membrane sites with a Kd of 0.01-0.02 microM and associates with a Kd of 0.5-4 microM to spectrin, microtubules and neurofilaments in in vitro assays. Synapsin interconnects synaptic vesicles to membranes, and this activity is inhibited by phosphorylation with Ca/calmodulin-dependent protein kinase. Synapsin may have a role in neurons as a structural protein capable of interconnecting small synaptic vesicles with a number of proteins, including spectrin, microtubules, neurofilaments, and membrane sites. A physiological function of synapsin could be as a vesicle-organizing protein that mediates calcium-regulated association of vesicles with cytoskeletal proteins during axonal transport and attaches vesicles to active zones in nerve endings.

Animals↗
PubMed1984

Pilot clinical trial with a new beta 2-sympathomimetic bronchodilator, mabuterol.

An open pilot study was performed on 10 patients with chronic, reversible, obstructive lung disease and known good response to beta 2-bronchodilators. The effects of 40, 60 and 80 micrograms 1-(4-amino-3-chloro-5-trifluoromethyl-phenyl)-2-tert.-butylamino-ethanol hydrochloride (mabuterol) given orally and of 0.4 mg fenoterol (aerosol) were measured on airway resistance, thoracic gas volume, pulse rate and blood pressure. Side effects, ECG and laboratory values were recorded. Mabuterol was found to have a good, clinically useful, bronchodilating effect and to possess excellent tolerability at doses of 40-60 micrograms.

Adrenergic beta-Agonists↗