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Biomedical subjects

G Taylor

Publications and source records attributed to G Taylor.

At least 217 records · Page 12Linked to original sources
PubMed1994

Conversion of anterior limb bud cells to ZPA signaling cells in vitro and in vivo.

Following a graft of posterior (zone of polarizing activity or ZPA) cells into the anterior margin of the developing chick wing bud, anterior cells are induced to alter their developmental fate and form structures that are normally composed of posterior cells. When anterior cells are cultured under microdissociation conditions they develop ZPA signaling ability within 24 hr. ZPA signaling in these cultures is transient and once established the level of ZPA signaling declines with time in culture. ZPA signaling in anterior cells is sensitive to treatment with fibroblast growth factor-2 (FGF-2); the development of ZPA signaling is inhibited when nonsignaling anterior cells are cultured in the presence of FGF-2. Conversely, when anterior cells that have developed ZPA signaling are treated with FGF-2, ZPA signaling levels are maintained. Thus, our results suggest that FGF-2 maintains or stabilizes the positional character of anterior (nonsignaling) cells, as well as anterior ZPA signaling converted cells, and posterior (ZPA signaling) limb bud cells in vitro (R. Anderson, M. Landry, and K. Muneoka (1993) Development 117, 1421-1433). In addition, anterior cells will convert to ZPA signaling cells in vivo following apical ectodermal ridge (AER) removal, suggesting that a factor(s) localized to the AER prevents anterior cells from developing ZPA signaling capability during limb outgrowth. These findings indicate that nonsignaling anterior limb bud cells have the potential to become ZPA signaling cells and that FGF-2, or a related factor, functions in the maintenance of positional states in the developing limb.

Animals↗
PubMed1994

Sequences of heavy and light chain variable regions from four bovine immunoglobulins.

Oligodeoxyribonucleotide primers based on the 5' ends of bovine IgG1/2 and lambda constant (C) region genes, together with primers encoding conserved amino acids at the N-terminus of mature variable (V) regions from other species, have been used in cDNA and polymerase chain reactions (PCRs) to amplify heavy and light chain V region cDNA from bovine heterohybridomas. The amino acid sequences of VH and V lambda from four bovine immunoglobulins of different specificities are presented.

Amino Acid Sequence↗
PubMed1994

Abnormal cardiac pain perception in syndrome X.

OBJECTIVES: The purpose of this study was to determine whether a diminished cardiac pain threshold contributes to chest pain in patients with syndrome X. BACKGROUND: There have been some reports of an altered pain perception in syndrome X. METHODS: Intracardiac catheter manipulation was performed in four groups of patients (syndrome X [group 1, 36 patients]; mitral valve disease and normal coronary arteries [group 2, 36 patients]; mitral valve disease and coronary artery disease [group 3, 36 patients]; and heart transplant recipients with normal coronary arteries [group 4, 36 patients]). Coronary flow velocity was measured in patients with syndrome X and in transplant recipients by use of an intracoronary Doppler catheter positioned in the left anterior descending coronary artery at intracardiac catheter manipulation. Coronary flow reserve in response to papaverine was also measured in patients with syndrome X and in transplant recipients. RESULTS: Intracardiac stimulation produced typical anginal chest pain in 34 group 1 (syndrome X) patients (94%). However, chest pain was produced only in five patients (14%) in group 2, seven patients (19%) in group 3 and no patients in group 4. There were no significant changes in coronary blood flow velocity associated with chest pain in group 1 patients. Coronary flow reserve in response to a hyperemic dose of intracoronary papaverine was significantly lower in the syndrome X group. There was no significant difference in the prevalence with which the stimulation tests produced chest pain in patients with syndrome X with an impaired coronary flow reserve or a positive radionuclide scan. CONCLUSIONS: The results of our study suggest that abnormal cardiac pain perception is a fundamental abnormality in syndrome X.

Adult↗
PubMed1994

Identification of type-2 phosphatidic acid phosphohydrolase (PAPH-2) in neutrophil plasma membranes.

Plasma membrane phosphatidic acid phosphohydrolase (PAPH) plays an important role in signal transduction by converting phosphatidic acid to diacylglycerol. PAPH-2, a Mg(2+)-independent, detergent-dependent enzyme involved in cellular signal transduction, is reportedly absent from the plasma membranes of neutrophilic leukocytes, a cell that responds to metabolic stimulation with abundant phospholipase D-dependent diacylglycerol generation. The present study was designed to resolve this discrepancy, focusing on the influence of cellular disruption techniques, detergent availability and cation sensitivity on the apparent distribution of PAPH in neutrophil subcellular fractions. The results clearly indicate the presence of two distinct types of PAPH within the particulate and cytosolic fractions of disrupted cells. Unlike the cytosolic enzyme, the particulate enzymes was not potentiated by magnesium and was strongly detergent-dependent. The soluble and particulate enzymes displayed dissimilar pH profiles. Separation of neutrophil particulate material into fractions rich in plasma membranes, specific granules and azurophilic granules by high speed discontinuous density gradient centrifugation revealed that the majority of the particulate activity was confined to plasma membranes. This activity was not inhibited by pretreatment with n-ethyl-maleimide in concentrations as high as 25 mM. PAPH activity recovered in the cytosolic fraction of disrupted neutrophils was almost completely inhibited by 5.0 mM n-ethylmaleimide. We conclude that resting neutrophils possess n-ethylmaleimide-resistant PAPH (type 2) within their plasma membranes. This enzyme may markedly influence the kinetics of cell activation by metabolizing second messengers generated as a result of activation of plasma membrane phospholipase D.

Cell Membrane↗
PubMed1994

Synthesis of novel water-soluble 7-(aminoacylhydrazono)-formyl camptothecins with potent inhibition of DNA topoisomerase I.

Eighteen new water-soluble 7-(aminoacylhydrazono)-formyl camptothecins were synthesized and evaluated for their ability to cause protein-linked DNA breaks and to inhibit topoisomerase I activity. Compared with camptothecin, five of the compounds were as potent or more potent in these tw assays but were less toxic in several cancer cell lines. The results suggest that the 7 position in the B ring is a suitable location for introducing a polar moiety into camptothecin producing analogues with enhanced topoisomerase I inhibiting activity.

Antineoplastic Agents↗
PubMed1994

Methicillin-resistant Staphylococcus aureus in tertiary care institutions on the Canadian prairies 1990-1992.

OBJECTIVE: To review experience with methicillin-resistant Staphylococcus aureus (MRSA) in tertiary acute-care teaching hospitals on the Canadian prairies. DESIGN: Retrospective review for a 36-month period, 1990 through 1992. SETTING: Five tertiary acute-care teaching hospitals in three Canadian prairie provinces. METHODS: MRSA isolates and susceptibility were identified through the clinical microbiology laboratory at each institution. For each patient, data collected included duration of institutional residence prior to isolation, patient ethnic background, age, sex, and antimicrobial susceptibility. Epidemiologic typing of strains used restriction fragment length polymorphism analysis by pulsed-field gel electrophoresis. RESULTS: Two hundred fifty-nine MRSA isolates were identified in 135 patients during the 36 months, with substantial institutional variation in number of isolates. No consistent increase in yearly numbers of isolates was apparent. Patients usually had MRSA identified at admission (62%); only one of five centers had the majority of isolates acquired nosocomially. Patients with MRSA present at admission were more frequently of aboriginal (First Nations) ethnicity (62% compared with 14% of nosocomial; P < 0.001). Pulsed-field gel electrophoresis of 167 isolates from 135 patients revealed 46 different strains with little interprovincial or interinstitutional identity of strains. CONCLUSIONS: MRSA isolated in patients in tertiary care institutions in these three Canadian provinces usually is acquired prior to admission. A disproportionate number of isolates are identified in aboriginal Canadians. Epidemiologic typing was consistent with a polyclonal origin of MRSA in this geographic area.

Adult↗
PubMed1994

Comparative risk of bloodstream infection in organ transplant recipients.

To determine relative rates and sources of nosocomial bloodstream infection in solid organ transplant recipients, concurrently collected data on 277 consecutive patients were reviewed. Twenty-eight patients developed 40 infections. Liver recipients experienced a higher rate (28%) than either kidney (5%) or heart, heart-lung (10%). Primary infections (60% overall) caused by gram-positive bacteria (59% overall) predominated at all three sites.

Alberta↗
PubMed1994

Antigenic heterogeneity of the attachment protein of bovine respiratory syncytial virus.

A panel of 23 monoclonal antibodies (MAbs) specific for the attachment (G) glycoprotein of bovine respiratory syncytial virus (BRS virus), recognizing seven antigenic areas on the G protein, was used to determine the antigenic heterogeneity among 19 BRS viruses isolated over a 20 year period from various parts of the world. The pattern of reactivity of the isolates, as determined by ELISA, identified two major subgroups of BRSV. This finding was confirmed by radioimmunoprecipitation of the G protein by the MAbs and was also demonstrated using polyclonal sera obtained from calves hyperimmunized with BRS virus strains from each subgroup. The subgroups could also be differentiated by differences in the apparent M(r) of the fusion (F) glycoprotein and its cleavage products. The apparent M(r)s of the F0, F1 and F2 polypeptides were 73K, 46K and 17K for subgroup A strains and 77K, 46K and 23K for subgroup B strains. These studies provide evidence for two major lineages of BRS virus, similar to the situation with human RS virus.

Animals↗
PubMed1994

Peak expiratory flow meters (PEFMs)--who uses them and how and does education affect the pattern of utilisation?

BACKGROUND: Asthma control may be assisted by educating patients to use peak expiratory flow meters (PEFMs). AIMS: To find out the sociodemographic and clinical characteristics of asthmatics attending an Emergency Room (ER) who owned PEFMs. METHODS: We undertook a study of 352 asthmatics aged seven to 55 years who attended an ER. The following were analysed: their pattern of peak flow monitoring (PFM), the factors associated with 'appropriate' or daily PFM on entry to the study and then prospectively; whether asthma education influenced utilisation and whether there was a reduction in ER use or admissions in those who acquired a PEFM. RESULTS: Those owning a PEFM at entry to the study (54%) had more asthma morbidity (p = 0.0001), had had asthma for longer (p = 0.0001), had seen their medical practitioners more often in the previous nine months (p = 0.0001), were on more asthma medications (p = 0.0001) and were more likely to have been to an Asthma Clinic (p = 0.0001). Those not owning a PEFM were more likely to be of lower social class (p = 0.016) and of Pacific Island origin (p = 0.0001) suggesting that distribution is not ideal and is influenced by disease severity, amount of health care use and sociodemographics. Patients with a self-management plan (35% of PEFM owners) and those receiving 'good care' or management, were more likely to use PFM 'appropriately' and to mention PFM in a scenario evaluating their response to worsening asthma control and argues for PEFMs to be distributed only in conjunction with a self-management plan, and therefore in close association with the patients' medical practitioners. Most patients (75%) appeared to prefer making management decisions based on symptoms rather than on their peak expiratory flow (PEF) and few (16%) performed daily PFM at entry to the study and fewer (6%) nine months later. There was an improvement in the pattern of PFM after education, but the acquisition of a PEFM made no difference to the frequency of ER use or admission. CONCLUSION: More realistic goals need to be defined in relationship to PFM which may improve patients' acceptance of the strategy, and therefore, hopefully their compliance. Such strategies need to be consistently reinforced over time for them to have an impact on asthma morbidity.

Adolescent↗
PubMed1994

The transactivator gene of human T-cell leukemia virus type I is more variable within and between healthy carriers than patients with tropical spastic paraparesis.

Human T-cell leukemia virus type I (HTLV-1) causes T-cell leukemia and tropical spastic paraparesis (TSP) in a minority of infected people, whereas the majority remain healthy. No association between a particular HTLV-I sequence and disease manifestation has been found in previous studies. We studied here the sequence variability of the gene for the HTLV-I Tax protein, which is the dominant target antigen of the very strong cytotoxic T-lymphocyte response to the virus. In HTLV-I infection, the intraisolate nucleotide variability is much greater than the variability between isolates. The predicted protein sequence of Tax was significantly more variable in the healthy seropositive individuals' provirus than in those of the patients with TSP. Thus, tax sequence heterogeneity, rather than the presence of particular sequences, distinguishes healthy HTLV-I-seropositive individuals from patients with TSP.

Base Sequence↗
PubMed1994

Antigenicity of the N8 influenza A virus neuraminidase: existence of an epitope at the subunit interface of the neuraminidase.

To locate antigenic epitopes on the N8 neuraminidase (NA), we generated a panel of 97 monoclonal antibodies (MAbs), 66 of which inhibited NA activity (NI antibodies). Three groups of NI MAbs were identified from their different reactivities with escape mutants. Group 1 antibodies recognized the peptide loop containing residues 344 to 346, which appears to be an immunodominant region on the rim of the enzyme center of the N8 NA. Group 2 antibodies recognized a novel epitope containing residues 150, 199, 367, 399, and 400 (N2 numbering). From the location of these residues on the three-dimensional structure of the N8 NA, the epitope appears to be located at the interface of two adjacent monomers in the tetrameric NA, one contributing residues 150 and 199 and the other contributing residues 367 and 399 to 400. The available evidence indicates that the MAbs of this group react with the NA only after it is fully assembled. The third group of antibodies recognized the peptide loops containing residues 367 and 399 to 400. All of the amino acid substitutions in N8 escape mutants which affect the NI activity of antibodies were located in the peptide loops known to form epitopes in the N2 and N9 subtypes, indicating that antigenic regions in the NA head inducing NI antibodies appear to be similar among different subtypes of influenza A viruses. The MAbs used in this study will be valuable in studying the role of each N8 NA epitope in host immune defense systems and in the kinetics analysis of the biosynthesis of the enzyme.

Amidohydrolases↗
PubMed1994

Primary peristalsis is the major acid clearance mechanism in reflux patients.

This study examined the clearance of gastric acid from the oesophagus in ambulant patients with gastro-oesophageal reflux. Eighteen patients with proved reflux disease were studied, nine with (group 1) and nine without (group 2) endoscopic oesophagitis. Oesophageal pressure and pH were recorded over 24 hours. Pressures were measured by a probe with five sensors: a 5 cm long sensor in the lower oesophageal sphincter, three sensors in the body of the oesophagus, and one at the pharynx to detect swallowing. Oesophageal pH was monitored 5 cm above the lower oesophageal sphincter. Manometric activities were classified as either peristaltic or ineffective. The latter included simultaneous, non-transmitted, and low amplitude peristaltic contractions. A reflux episode was defined as starting when pH fell to less than 4 and ending when the pH rose to 5. When the rise to pH 5 took place in three or more discrete steps after motor responses to gastro-oesophageal reflux, the pH steps were labelled as initial change (I), middle changes (M), and last change (L). A total of 595 episodes of gastro-oesophageal reflux and 1626 associated motor events were analysed. Of these, 1331 (81.9%) were classed as primary peristaltic activity, 174 (10.7%) as primary ineffective activity, 46 (2.8%) as secondary peristaltic activity, and 75 (4.6%) as secondary ineffective activity. There were no significant differences in initial change (p > 0.05), middle changes (p > 0.05), and last change (p > 0.05) between group 1 and group 2. In all patients, the successive changes of pH in response to motor activity were significantly different (p = 0.0001) between initial, middle, and last changes. Last change was significantly higher when compared with initial (p=0.001) and middle changes (p<0.001). Primary oesophageal peristalsis was the most frequent motor response to gastro-oesophageal reflux. The last motor activity during reflux showed the greatest change in pH.

Adult↗
PubMed1994

Prospective controlled evaluation of the effect of a community based asthma education centre in a multiracial working class neighbourhood.

BACKGROUND: Previous work has indicated a high rate of non-attendance at hospital based clinics among young, multiracial asthmatic patients of lower socioeconomic class. The efficacy of delivering asthma education from a community health centre established in a multiracial working class neighbourhood was evaluated. METHODS: A prospective controlled study was performed in which asthmatic subjects aged between two and 55 years attending a hospital emergency room with acute asthma and living within a defined geographical area of high emergency room users were randomised to the usual follow up or the education centre plus usual follow up. Measurements were taken at entry into the study and again nine months later. RESULTS: At nine months patients randomised to the education centre had more preventive medications, more peak expiratory flow meters and better flow meter technique, more self-management plans, better knowledge of appropriate action to take when confronted with worsening asthma, less nocturnal awakening, and better self-reported asthma control than the control group. There was no difference between the study groups in measurements of compliance, hospital admission, days lost from school or work, or emergency room use. CONCLUSIONS: The main effects of education were on asthma knowledge and self-management skills, whilst improvements in asthma morbidity were small. Potential reasons for this include heterogeneous study population (in terms of baseline self-management skills, asthma severity, ethnicity and age), pragmatic study design, insensitivity of many of the measurements of morbidity, the modest effectiveness of a single time limited education programme, and inability to limit the effects of such a large community based study to the intervention group (there was a 67% reduction in asthma admissions during the study period from the geographical area targeted compared with a 22% reduction for the rest of Auckland).

Adolescent↗
PubMed1994

Effect of transcutaneous electrical nerve stimulation on coronary blood flow.

BACKGROUND: Although neurostimulation has been shown to be of benefit in angina pectoris, the exact mechanism of its action is not clear. This study was performed to examine the effect of transcutaneous electrical nerve stimulation on coronary blood flow. METHODS AND RESULTS: The effect of transcutaneous electrical nerve stimulation was studied in 34 syndrome X patients (group 1), 15 coronary artery disease patients (group 2), and 16 heart transplant patients (group 3). Coronary blood flow velocity (CBFV) in the left coronary system was measured at rest and after a 5-minute stimulation period with a Judkins Doppler. There was a significant increase in the resting CBFV in group 1 (from 6.8 +/- 4.1 to 10.5 +/- 5.7 cm/s, P < .001) and group 2 (from 6.8 +/- 4.1 to 10.5 +/- 5.7 cm/s, P < .001). However, there was no significant change in the resting CBFV in group 3. There were no significant changes in the coronary arterial diameters as a result of neurostimulation. There was a significant decrease in the epinephrine levels in group 1 (from 79.6 +/- 17.8 to 58.5 +/- 17.5 ng/L, P = .01) and group 2 (from 102.2 +/- 27.2 to 64.1 +/- 19.1 ng/L, P = .01). CONCLUSIONS: Transcutaneous electrical nerve stimulation can increase resting coronary blood flow velocity. The findings suggest that the site of action is at the microcirculatory level and that the effects may be mediated by neural mechanisms.

Aged↗
PubMed1994

Six-month clinical and angiographic follow-up after direct angioplasty for acute myocardial infarction. Final results from the Primary Angioplasty Registry.

BACKGROUND: After direct angioplasty in the setting of acute myocardial infarction, patients were followed clinically and angiographically for 6 months at six experienced centers to evaluate outcomes. METHODS AND RESULTS: Of 258 patients with 6-month follow-up after surviving initial hospitalization, 5 (2%) died, 8 (3%) had nonfatal infarctions, 56 (22%) had chest pain, of whom 25 (10%) required hospitalization, and 42 (16%) patients needed repeat angioplasty. Of 203 eligible patients, 154 (76%) had angiographic follow-up. The infarct-related artery remained patent (defined as TIMI 2 or 3 flow) in 87%, while 13% developed reocclusion (TIMI 0 or 1 flow) by 6 months after discharge. Patients with reocclusion were more likely to have adverse events, including 35% with clinically evident reinfarction and 59% requiring repeat angioplasty. The median ejection fraction improvement from acute to follow-up study was 6%, with no improvement in patients with a reoccluded infarct-related artery and an 8% improvement in patients with a patent infarct-related artery. CONCLUSIONS: The positive clinical outcomes recorded immediately after direct angioplasty persisted through 6 months of follow-up. Although the incidence of clinical end points was equivalent to or lower than thrombolytic therapy trials, restenosis is a substantial problem. These findings provide evidence beyond the initial hospitalization that direct angioplasty is a reasonable choice for the treatment of acute myocardial infarction.

Aged↗
PubMed1994

Tumor necrosis factor alpha regulation of immunoglobulin secretion in trauma patients.

Major trauma-related immune dysfunction is observed at the time of augmented release of immunopathologic mediators. In the present study, T cell-dependent immunoglobulin (Ig) synthesis in peripheral blood mononuclear cell (PBMC) cultures from blunt trauma patients (N = 12, injury severity score (ISS) 27-50), was reduced by 30- > 90%. This coincided with significantly (P < 0.001-0.01) elevated secretion of the biologically active tumor necrosis factor alpha (TNF alpha). Modulation of the TNF alpha activity by anti-TNF alpha antibody (anti-TNF alpha Ab) led to dose-dependent alterations in IgG synthesis. IgG production increased (up to 300%) in cultures treated with 0.5-2 micrograms/ml of the antibody, where low levels of TNF alpha activity often persisted. However, immunoglobulin synthesis was eradicated in preparations exposed to higher concentrations (10 micrograms/ml) of anti-TNF alpha Ab and devoid of TNF alpha biological activity. The treatment with anti-TNF alpha Ab had no effect on mitogen- or alloantigen-induced PBMC proliferation. Thus, in severely traumatized patients, biological activities of endogenous TNF alpha may include modulation of T cell-dependent B lymphocyte function. Immunoregulatory potential of TNF alpha should, therefore, be considered in therapeutic strategies to abrogate its activity.

Adult↗