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Biomedical subjects

G Taylor

Publications and source records attributed to G Taylor.

At least 181 records · Page 10Linked to original sources
PubMed1996

Hypertonic saline improves brain resuscitation in a pediatric model of head injury and hemorrhagic shock.

INTRODUCTION: Brain injury accompanied by hypovolemic shock is a frequent cause of death in multiply injured children. Hypertonic saline (HTS) has been shown to return hemodynamics to normal in adult models, without increasing intracranial pressure (ICP) as seen with crystalloids. To assess fluid resuscitation, the authors evaluated HTS versus lactated Ringer's solution (LR) with respect to hemodynamics and cerebrovascular hemoglobin oxygen saturation (Sco2) in anesthetized, head-injured, 1-month-old piglets. METHODS: Group 1 (n = 6) was studied for 3.5 hours after a cryogenic brain injury and no shock. Groups 2 and 3 had cryogenic brain injury followed by hemorrhagic shock, in which mean arterial pressure (MAP) was reduced to 40 to 50 mm Hg and maintained for 30 minutes. Group 2 (n = 5) was then resuscitated with 1 mL of 7.5% HTS per 1 mL of blood loss. Group 3 (n = 6) was resuscitated with 3 mL of LR per 1 mL of blood loss. Sco2 was determined by near-infrared spectroscopy in the injured region of the brain. All data were analyzed using analysis of variance with repeated measures. RESULTS: MAP, ICP, temperature, serum sodium, and cardiac output (CO) were similar in all groups during baseline and between groups 2 and 3 during shock. After resuscitation, MAP, CO, and core temperature were similar in all three groups, and serum sodium was increased in the HTS group (by 29%). Sco2 increased transiently after cryogenic injury in all groups, then gradually decreased to below baseline. After shock, Sco2 decreased precipitously in group 2 and 3. After resuscitation, Sco2 was different in the two resuscitation groups, increasing in the HTS group, above baseline values, but remaining below baseline values in the LR group (P < .002). ICP was lowered by HTS resuscitation and increased by LR resuscitation (P < .002) CONCLUSION: In our model of head injury and shock, resuscitation with either HTS or LR restored MAP and CO to control levels. However, during shock, the injured brain was severely deoxygenated, and administration of HTS restored cerebral oxygenation whereas LR did not, reflecting improved cerebral resuscitation by HTS without elevating ICP. The data suggest that HTS is a better resuscitation fluid than LR in head-injured children with hemorrhagic shock.

Animals↗
PubMed1996

Cross validation of the factor structure of the 20-item Toronto Alexithymia Scale: an Italian multicenter study.

The 20-item Toronto Alexithymia Scale (TAS-20) has been shown in previous research to measure a general dimension of alexithymia with three intercorrelated factors. This study evaluated the reliability and factorial validity of an Italian translation of the TAS-20 in a group of normal adults (N = 206) and in a mixed group of medical and psychiatric outpatients (N = 642). Using confirmatory factor analyses, the previously established three-factor model of the TAS-20 was found to be replicable in both groups. In addition, the Italian TAS-20 demonstrated adequate estimates of internal reliability and test-retest reliability. Although evaluation of the convergent, discriminant, and concurrent validity of the TAS-20 is required in Italian populations, the present results support the use of the Italian translation of the scale for clinical and research purposes.

Adult↗
PubMed1996

Influence of selective T-lymphocyte depletion on the lung pathology of gnotobiotic calves and the distribution of different T-lymphocyte subsets following challenge with bovine respiratory syncytial virus.

The depletion of CD8+ T-lymphocytes with a murine monoclonal antibody (mAb) specific for the CD8 molecule delayed the ability of three gnotobiotic calves to clear bovine respiratory syncytial virus (BRSV) from their lungs within 10 days after an experimental challenge with the virus. This protracted infection was associated with an enhanced pneumonic consolidation score (21.6 per cent) compared with seven control calves (7.4 per cent) and a histological lesion of active respiratory epithelial hypertrophy. Three gnotobiotic calves depleted of the CD4+ subpopulation with the appropriate mAb also had enhanced macroscopic lesions (16.6 per cent) but the histological lesion was less active. The depletion of the gamma/delta TCR+ WC1+ subpopulation had no apparent effect on the macroscopic or microscopic pulmonary lesions. Although the depletion of the CD8+ or the CD4+ subpopulations enhanced the pulmonary lesions, no clinical signs of respiratory disease were detected. Immunoperoxidase labelling and image analysis of the lymphocyte subpopulations in lung tissue revealed an increase in the number of CD8+ T cells after the infection of non-depleted, control calves, especially in the lamina propria of the large bronchioles. Calves depleted of individual lymphocyte subsets and infected with BRSV showed no compensatory increase in the remaining subpopulations and no lymphoreticular hyperplasia.

Animals↗
PubMed1996

Identification of potential CTL epitopes of bovine RSV using allele-specific peptide motifs from bovine MHC class I molecules.

Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infection in young infants and housed calves. Depletion of CD8+ lymphocytes from calves inhibited their ability to clear the virus from the nasopharynx and lungs. To study these cells further, a cytotoxic T lymphocyte (CTL) assay was established. CTL could be demonstrated in the peripheral blood of gnotobiotic calves 7-10 days post infection (p.i.) with RSV and in lungs 10 days p.i. This response was both MHC-restricted and virus-specific. Following separation of the lung lymphocytes by magnetic activated cell sorting, it was shown that the cytolytic activity was mediated by cells of the CD8+ phenotype. To identify epitopes recognised by bovine CTL, the consensus motifs from MHC class I alleles found in the herd at Compton were identified. cDNA libraries were constructed and screened for full length class I sequences. The isolated cDNA clones were then transfected into mouse P815 cells and the expressed product immunoprecipitated and matched with a serological specificity. The bovine MHC class I molecules were isolated from lysed transfected cells by affinity chromatography, using a monoclonal antibody specific for bovine MHC class I, and bound peptides were separated by reverse-phase HPLC. Analysis of the protein sequences of bovine RSV for the defined motifs has identified potential CTL epitopes.

Alleles↗
PubMed1996

Subgrouping of bovine respiratory syncytial virus strains detected in lung tissue.

Bovine respiratory syncytial virus is an important respiratory pathogen in cattle. Recently, subgroups of BRSV have been identified, based on antigenic differences. However, little is known about subgroups of BRSV that circulate in the cattle population. Therefore, we determined the reactivity of monoclonal antibodies (mAbs), directed against the G, F, or P protein of BRSV, with lung tissue from 47 calves, that suffered from severe respiratory disease. Fourteen animals (30%) proved to be infected with BRSV, because they all reacted with mAbs against the P or F protein, as detected by fluorescent antibody tests. Monoclonal antibodies against the G protein were able to discriminate between the BRSV-positive specimens: 7 strains were identified as subgroup A strains, and 5 strains as subgroup AB, which is introduced as BRSV subgroup in this paper. Two strains could not be identified unambiguously. It is concluded that BRSV subgroup A and AB were associated with severe respiratory disease, and that strains belonging to either subgroup circulated concurrently in the cattle population in the Netherlands.

Animals↗
PubMed1996

Aging-associated endothelial dysfunction in humans is reversed by L-arginine.

OBJECTIVES: This study investigated the hypothesis that aging selectively impairs endothelium-dependent function, which may be reversible by administration of L-arginine. BACKGROUND: An impaired response to acetylcholine with aging has been demonstrated in humans. However, the mechanisms underlying this impaired response of the coronary microvasculature remain to be determined. METHODS: We infused the endothelium-independent vasodilators papaverine and glyceryl trinitrate (GTN) and the endothelium-dependent vasodilator acetylcholine (1,3,10 and 30 micrograms/min) into the left coronary artery of 34 patients (27 to 73 years old) with atypical chest pain, negative exercise test results, completely normal findings on coronary angiography and no coronary risk factors. Coronary blood flow was measured with an intracoronary Doppler catheter. The papaverine and acetylcholine infusions were repeated in 14 patients (27 to 73 years old) after an intracoronary infusion of L-arginine (160 mumol/min for 20 min). RESULTS: There was a significant negative correlation between aging and the peak coronary blood flow response evoked by acetylcholine (r = -0.73, p < 0.0001). However, there was no correlation to papaverine (r = -0.04, p = 0.82) and GTN (r = -0.24, p = 0.17). The peak coronary blood flow response evoked by acetylcholine correlated significantly with aging before L-arginine infusion (r = -0.87, p < 0.0001), but this negative correlation was lost after L-arginine infusion (r = -0.37, p = 0.19). CONCLUSIONS: The results suggest that aging selectively impairs endothelium-dependent coronary microvascular function and that this impairment can be restored by administration of L-arginine, a precursor of nitric oxide.

Acetylcholine↗
PubMed1996

Sialidases: structures, biological significance and therapeutic potential.

The structure-based design of a potent inhibitor of the influenza-virus neuraminidase (sialidase) is one of the outstanding successes of rational drug design. Recent clinical trials of the drug have stimulated many companies to seek a share of the potentially huge flu market. Sialidases, however, are involved in the pathogenesis of a whole range of other diseases, so perhaps the knowledge and expertise gained from the influenza story can be used in the design of other drugs, given that they all share certain structural features.

Binding Sites↗
PubMed1996

Pulmonary first-pass and steady-state metabolism of phenols.

PURPOSE: To study (A) the effect of the administration route (i.v. and i.t.) on pre- and post-absorptive metabolism of phenol and 1-naphthol by the lung and (B) pulmonary extraction of phenol at steady-state. METHODS: Phenols were administered intra-arterially, intravenously and intratracheally and the pre- and post-absorptive metabolism assessed by comparing the AUCs in arterial blood. Phenol was infused to steady-state and the pulmonary extraction assessed by measuring jugular vein and carotid artery blood concentrations. RESULTS: In contrast to previously published data (e.g., Mistry and Houston, Drug Metab.Dispos.l3:740-745 (1985)) we could not detect pulmonary first-pass metabolism of the phenols; reasons for this disparity are discussed. An apparent negative pulmonary extraction of phenol at steady-state was observed, probably as a consequence of extraction by organs which are in series, and not parallel, with the lungs (e.g. liver, kidneys and GIT). CONCLUSIONS: (A) Phenol and 1-naphthol do not undergo pulmonary first-pass metabolism. (B) Traditional methods of assessing organ extraction and clearance at steady-state cannot be utilised when metabolising organs are in series.

Animals↗
PubMed1996

Primary cytotoxic T-cell responses to bovine respiratory syncytial virus in calves.

Bovine respiratory syncytial virus (RSV) is a major cause of respiratory disease in young calves. Recent studies in calves, in which different T-cell subsets were depleted, have shown that CD8+ T cells play a central role in recovery from RSV infection. The present study demonstrates that RSV-specific, major histocompatibility complex-restricted cytotoxic T cells appear in the peripheral blood of gnotobiotic calves 7-10 days after infection with bovine RSV and were also detected in the lungs 10 days after infection. The cytotoxic T lymphocytes (CTL) recognized antigenically distinct strains of bovine RSV. There was no correlation between either the level of CTL activity in the lung or the development of CTL in the peripheral blood and the extent of pneumonic consolidation. The demonstration of CD8+ CTL in the lungs at a time when bovine RSV has been cleared confirms the importance of these cells in recovery from infection.

Animals↗
PubMed1996

Mutant forms of the F protein of human respiratory syncytial (RS) virus induce a cytotoxic T lymphocyte response but not a neutralizing antibody response and only transient resistance to RS virus infection.

Vaccinia virus (vv) recombinants expressing either wild-type (VA-F) or mutant forms (VA-FT, VA-FR47, VA-FS1 to VA-FS6) of the fusion (F) protein of respiratory syncytial (RS) virus were examined for their ability to elicit antibody, cytotoxic T lymphocytes (CTL) and protection against RS virus infection in BALB/c mice. Cells infected with the VA-F and VA-FT recombinants expressed the F protein on their surface and mice vaccinated with these recombinants developed RS virus neutralizing antibodies. The VA-FR47 recombinant expressed a mutant form of the F protein (with six amino acid changes from the wild-type) in which both proteolytic processing of the F0 precursor and its transport to the cell surface were inhibited. These mutants induced transient protection against RS virus infection although they did not induce RS virus neutralizing antibodies, or antibodies detectable by ELISA. All the vv recombinants were able to induce an RS virus-specific, MHC class I restricted CTL response. Vaccination of mice with a second set of vv recombinants expressing mutant forms of the F protein showed that the replacement Phe to Ser at amino acid 237 either alone or in combination with others abolished the neutralizing antibody response but did not affect priming of CTLs. These results demonstrate that long-term protection against RS virus infection in mice vaccinated with recombinant vv expressing the F protein is more dependent upon the induction of an antibody rather than a CTL response.

Animals↗
PubMed1996

Coronary flow reserve and oesophageal dysfunction in syndrome X.

The relative prevalence of abnormalities of coronary flow reserve and oesophageal function was ascertained in 32 syndrome X patients with typical angina chest pain, a positive exercise test, and normal coronary arteries. Coronary flow reserve in response to a hyperaemic dose of papaverine was measured using an intracoronary Doppler catheter positioned in the left anterior descending coronary artery. An abnormal coronary flow reserve was defined as being < 3.0. Patients were investigated for oesophageal dysfunction by manometry and 24-hour pH monitoring. Thirteen patients had an impaired coronary flow reserve (group 1) and 19 patients had a normal flow reserve (group 2). Eight of the 13 group 1 patients (62%) and 13 of the 19 group 2 patients (68%, p = NS) had evidence of oesophageal dysfunction on either manometry or pH studies. Therefore, a total of 26 (81%) syndrome X patients had either an abnormality of coronary flow reserve or oesophageal dysfunction suggesting that chest pain in these patients may be due to myocardial ischaemia or oesophageal dysfunction, thus confirming the heterogeneous nature of this syndrome. The prevalence of oesophageal abnormalities was independent of any abnormalities of coronary flow reserve.

Adult↗
PubMed1996

Colour Doppler ultrasound in renal artery stenosis: intrarenal waveform analysis.

Renal artery stenosis (RAS) is the commonest secondary cause of hypertension and may result in renal ischaemia with resultant renal failure. Recent studies hve suggested that colour Doppler ultrasound, with spectral analysis of the intrarenal waveforms, can identify those patients with a significant RAS. A prospective study was performed in which colour Doppler ultrasound was compared with angiography in 73 patients (143 kidneys) presenting for renal angiography. Colour Doppler ultrasound was unsuccessful in 16% of kidneys due to a combination of technical failures and small kidney size. Accessory renal vessels were present in 14% of kidneys on angiography but none was detected by ultrasound. Of the 120 kidneys that had both examinations, no significant difference in intrarenal pulsatility or resistive index was noted between the angiographically stenosed and normal arteries. There were significant differences for intrarenal peak and end diastolic velocities, and acceleration time and index. Of these measurements, acceleration time was the best indicator of RAS. The probability of detecting a high grade RAS in an individual patient did not reach 90% until the acceleration time was prolonged to more than 0.12 s. Intrarenal colour Doppler ultrasound is not a general screening test for RAS and it should be reserved for selected patient groups where the incidence of disease is high. Patients with prolonged acceleration times of more than 0.12 s have a high likelihood of at least 70% RAS and should proceed directly to angiography.

Adult↗
PubMed1996

Aging of the brain-testicular axis: reproductive systems of healthy old male rats with or without endocrine stimulation.

To test the hypothesis that endocrine declines in males are incidental to disease, 24 gonadally intact old (22-24 months) rats were selected on the basis of good general health and assigned to one of three groups. One group of aged males was left untreated for comparison with an untreated control group of young adult males. Results from multiple measures of sociosexual behavior and reproductive physiology indicated that endocrine declines in males are not simply a by-product of increased disease incidence with aging. The untreated old animals showed clear decrements on all 13 measures of hypothalamic-pituitary- testicular (HPT) activity. The other two groups of old males were used to compare responsiveness of the aging HPT axis in healthy males to supplements with a typical exogenous (ExT) androgen regimen (300 micrograms testosterone/kg body wt/SC/daily/6 weeks) or to social stimulation (brief daily exposure to an inaccessible estrous female) for additional episodes of endogenous (EnT) hormone. Neither treatment restored our disease-free old male rats to levels approximating those of untreated young adults. Nonetheless, both treatments activated the aging HPT axis. EnT males showed increases in sociosexual behaviors, growth of androgen-sensitive bulbospongiosus muscle, and elevation of epididymal sperm reserves. ExT males, on the other hand, experienced a more foreboding hypertrophy of the ventral prostate gland. Our conclusion is that endocrine aging in males is ubiquitous and inevitable. Still, aged androgen-sensitive systems of healthy old rats retain notable capacity, particularly, for endogenous activation. Evidence points to functional responses by healthy aged males to the presence of sexually receptive females that, although not quantitatively the same, are qualitatively similar to the responses of young adult males.

Aging↗
PubMed1996

Geriatric-patient flow-rate modelling.

We consider the application of a three-compartment mathematical model using difference equations in discrete time to model the flow of patients through departments of geriatric medicine. It has been shown empirically that the time spent in hospital since admission may be described by a two-term mixed-exponential distribution. Previous work has explained this empirical finding in terms of a two-compartment model of geriatric in-patient behaviour where the two compartments are acute/rehabilitative and long-stay care. Our model extends this approach by considering patients released from geriatric departments and their subsequent length of stay in the community. We have therefore, two states of patient behaviour while in hospital: (i) patients can be admitted to the acute-rehabilitative state, from which they may die or be released back into the community; (ii) patients can be admitted to the long-stay state, from which they eventually die. The community state currently has only one state, from which patients may be readmitted back into the geriatric department or they may die. The model may then be used to estimate the average numbers and lengths of stay for short-term and long-term patients and the average number and length of stay in the community for released patients, allowing for a significant improvement in the forecasting of future bed requirements to aid the planning of geriatric departments.

Aged↗
PubMed1995

The three domains of a bacterial sialidase: a beta-propeller, an immunoglobulin module and a galactose-binding jelly-roll.

BACKGROUND: Sialidases, or neuraminidases, have been implicated in the pathogenesis of many diseases, but are also produced by many non-pathogenic bacteria. Bacterial sialidases are very variable in size, often possessing domains in addition to the catalytic domain. The sialidase from the non-pathogenic soil bacterium Micromonospora viridifaciens is secreted in two forms with molecular weights of 41 kDa or 68 kDa, depending on the nature of the carbohydrate used to induce expression. RESULTS: We report here the X-ray crystal structures of the 41 kDa and 68 kDa forms of the sialidase from M. viridifaciens at 1.8 A and 2.5 A resolution respectively. In addition, we report a complex of the 41 kDa form with an inhibitor at 2.0 A resolution, and a complex of the 68 kDa form with galactose at 2.5 A. The 41 kDa form shows the canonical sialidase beta-propeller fold. The 68 kDa form possesses two additional domains, one with an immunoglobulin-like fold that serves as a linker to the second, which is homologous to the galactose-binding domain of a fungal galactose oxidase. CONCLUSIONS: The presence of the additional carbohydrate-binding domain in the 68 kDa form of the bacterial sialidase reported here is a further example of a combination of carbohydrate binding and cleaving domains which we observed in the sialidase from Vibrio cholerae. This dual function may be common, but only to other bacterial and parasitic sialidases, but also to other secreted glycosidases involved in pathogenesis. The bacterium may have acquired both the immunoglobulin module and the galactose-binding module from eukaryotes, as the enzyme shows a remarkable similarity to a fungal galactose oxidase which possesses similar domains performing different functions and assembled in a different order.

Amino Acid Sequence↗