Search PubMed⌕ Search

Biomedical subjects

M Bailey

Publications and source records attributed to M Bailey.

At least 109 records · Page 6Linked to original sources

T-cell populations in the pig intestinal lamina propria: memory cells with unusual phenotypic characteristics.

We have previously presented evidence of a highly organized and compartmentalized structure of the small intestinal lamina propria of the pig. In this study, we conducted a detailed analysis of the T-cell populations found at this site, and compared these T cells with cell populations found in other tissue sites and the periphery. We showed that the CD4+ and CD8+ T-cell populations found in the pig gut are of memory phenotype, defined by CD45 isoform expression, but show few signs of recent activation. They show a high degree of phenotypic and therefore presumably functional homogeneity. Both CD4- and CD8-positive cells show strong parallels in the patterns of surface molecule expression, suggesting similar pressures on differentiation. The unique combination of surface molecules found on lamina propria T cells is found only infrequently on cells in other lymphoid sites.

Animals↗

Gender differences in knee cartilage volume as measured by magnetic resonance imaging.

OBJECTIVE: The aim of this study was to analyze sex differences in knee cartilage volume. METHODS: Articulate cartilage volumes were determined by processing images acquired in the sagittal plane using T1-weighted fat saturation magnetic resonance on an independent work station. The knees of 28 subjects (17 male, 11 female) who underwent MRI for clinical indications (pain <3 months) but who had a normal X-ray and structurally normal MRI were examined. RESULTS: Males had significantly larger cartilage volumes than females, with difference in cartilage volume remaining statistically significant after adjusting for age, height, weight and bone volume. The differences for males relative to females were: femoral cartilage volume [4.1 ml 95% CI (2.0, 6.1)]; and patella cartilage volume [1.4 ml (0.2, 2.7)]. Although not statistically significant, the tibial cartilage volume also showed these sex differences. Exploratory analysis indicated an increasing gender difference with increasing age for patellar cartilage volume. CONCLUSION: Men have significantly larger knee cartilage volume than women, independent of body and bone size. The mechanisms for this will need to be determined.

Adult↗

Assessment of long-term bronchiolar clearance of particles from measurements of lung retention and theoretical estimates of regional deposition.

Twelve healthy nonsmokers inhaled monodisperse Teflon particles labelled with 51Cr (half-life 27.8 days) with an aerodynamic diameter (dae) of 6.1 microns, 5 at a normal flow, 0.5 L/s, and 7 at an extremely slow flow, 0.05 L/s. Lung retention after 24 hours was measured for about 6 months and could be well described by a 2-component exponential function. After the normal inhalation, 14% of the particles retained after 24 hours cleared with a half-time of 3.7 days and 86% with a half-time of 217 days. After the slow inhalation, 35% of the particles retained after 24 hours cleared with a half-time of 3.6 days and 65% with a half-time of 170 days. Deposition was calculated using 3 different models including the recent Human Respiratory Tract Model (HRTM), adopted by the International Commission on Radiological Protection (ICRP), and a model based on Monte Carlo particle transport, together with an asymmetric lung model. Generally, the 3 models agreed fairly well and predicted a considerably higher deposition in the bronchiolar region (generations 9-15) at the slow flow than at the normal flow. Together, the experimental data and the predictions of the deposition models indicate that about 40% of the particles deposited in the conducting airways during the slow inhalation were retained after 24 hours. They also strongly indicate that the particles which cleared with a half-time of about 4 days were mainly deposited in the bronchiolar region, and that about 25% of the particles deposited in the bronchiolar region cleared in this phase. The experimental data agreed quite well with the HRTM predictions made using its default parameter values for slow clearance in the bronchial tree.

Administration, Inhalation↗

The relationship between distal tubular proton secretion and dietary potassium depletion: evidence for up-regulation of H+ -ATPase.

BACKGROUND: Dietary potassium depletion is associated with elevated plasma bicarbonate concentration and enhanced bicarbonate reabsorption in the distal tubule. The relationship between distal proton secretion and potassium status was investigated by in vivo microperfusion of the superficial distal tubule. METHODS: Experiments were performed on anaesthetized rats that had been maintained on either a low-potassium or control diet for 3-5 weeks prior to experimentation. The distal tubules were perfused at 10 nl/min with either a standard or a barium chloride-containing solution, and the late distal tubular transepithelial potential difference (Vte) and pH of the luminal fluid were recorded using a double-barrelled voltage and ion-sensitive microelectrode. RESULTS: In control rats, the Vte was -40.7+/-2.4 mV and the tubular fluid pH was 6.44+/-0.07; in potassium-depleted animals, the Vte was -15.0+/-1.4 mV and the pH was 6.76+/-0.03. The pH values in both groups of animals were significantly lower than would be predicted from the Vte and systemic pH for passive H+ distribution, indicating active proton secretion. Moreover, in hypokalaemic rats, this difference from predicted pH was significantly greater than in control animals (control = 0.27+/-0.06 vs. low-potassium = 0.46+/-0.03; P<0.01), suggesting enhanced active proton secretion. During perfusion with a solution containing BaCl2, the late distal tubule Vte became lumen positive in potassium-depleted rats, contrasting with an increased lumen negativity in potassium-replete controls. The barium-induced lumen-positive potential difference observed in the hypokalaemic rats was abolished by intravenous administration of acetazolamide. CONCLUSION: These data are consistent with enhanced electrogenic proton secretion (H+ -ATPase) during dietary potassium deprivation.

Animals↗

Marked prolongation of the succinylcholine effect two hours after neostigmine reversal of neuromuscular blockade in a patient with chronic renal insufficiency.

Prolonged neuromuscular blockade from succinylcholine after neostigmine administration has been reported in patients with frank renal failure. We present a case of prolonged neuromuscular blockade from succinylcholine administration, given 2 hours after neostigmine reversal of neuromuscular blockade in a patient with chronic renal insufficiency. This case shows that patients with chronic renal insufficiency, like patients with renal failure, are at risk for prolonged succinylcholine blockade if they have recently received anticholinesterase reversal of neuromuscular blockade. Administration of succinylcholine for facilitation of urgent endotracheal intubation may be required soon after reversal of nondepolarizing muscle relaxants, particularly in patients who return to the operating room for emergency care.

Aged↗

A reliable and valid home visit report for studies of asthma in young adults.

Validated instruments are not available to assess the residential characteristics. The aim of this study was to assess the reliability and validity of an interviewer-administered home visit report. The validity of 48 items in the Home Visit Report was examined against: observations made by a researcher, measurements of relative humidity, cat allergen, and ergosterol, a biomaker of fungal exposure and a biochemical test. Test-retest reliability of 10 fixed residential characteristics was assessed comparing the responses obtained in the main study with the pilot study, Kappa, ANOVA and Wilcoxon Rank Sum tests were applied to assess the agreement and P < 0.05 was considered as statistically significant. Among 44 items examined for the validity against observations, there was a perfect or almost perfect agreement in 21 (kappa = 0.9-1) and substantial agreement (kappa = 0.6-0.8) in 19. Higher cat allergen levels were observed with cat ownership and cat being allowed indoors. Observed condensation was associated with relative humidity and observed mould was associated with ergosterol levels. The agreement on the type of carpet and the test was substantial (kappa = 0.6). Among 10 items examined for reliability, there was a perfect or almost perfect agreement in 9 (kappa = 0.9-1) and substantial agreement (kappa = 0.7) in one. In conclusion, the Home Visit Report validated in this study provides reliable and valid data.

Adult↗

An antiinflammatory effect of salmeterol, a long-acting beta(2) agonist, assessed in airway biopsies and bronchoalveolar lavage in asthma.

The addition of long-acting beta(2) agonists to inhaled corticosteroid (ICS) therapy in symptomatic patients with asthma improves clinical status more than increasing the dose of ICS. It has been suggested that these benefits could be at the cost of an increase in airway inflammation, but few histopathological studies have been performed in the relevant group. In a double-blind, parallel-group, placebo-controlled study, we randomly assigned 50 symptomatic patients with asthma who were receiving ICS (range, 100 -500 microgram/d) to 12 wk of supplementary treatment with salmeterol (50 microgram twice daily) or fluticasone (100 microgram twice daily) or placebo. Bronchial biopsies and BAL were obtained from 45 patients before and after treatment and analyzed. After treatment with salmeterol there was no deterioration of airway inflammation as assessed by mast cells, lymphocytes, or macrophages in BAL or biopsies, but rather a significant fall in EG1-positive eosinophils in the lamina propria (from a median 18.3 to 7.6 cells/mm, p = 0.01), which was not seen after treatment with fluticasone. The only cellular effect of added fluticasone was a decrease in BAL lymphocyte activation. There was a concurrent improvement in clinical status, more marked with salmeterol than with increased ICS. Thus, adding salmeterol to ICS is not associated with increased "allergic" airway inflammation, but conversely with a complementary antieosinophil effect.

Adrenergic beta-Agonists↗

Studies on the C-terminal of hexapeptide inhibitors of the hepatitis C virus serine protease.

Replacement of the C-terminal carboxylic acid functionality of peptide inhibitors of hepatitis C virus (HCV) NS3 protease (complexed with NS4A peptide cofactor) by activated carbonyl groups does not produce any substantial increase in potency. These latter inhibitors also inhibit a variety of other serine and cysteine proteases whereas the carboxylic acids are specific. Norvaline was identified as a chemically stable replacement for the P1 residue of Ac-DDIVPC-OH which was also compatible with activated carbonyl functionalities.

Cysteine↗

Peptide-based inhibitors of the hepatitis C virus serine protease.

Hexapeptide DDIVPC-OH is a competitive inhibitor of the hepatitis C virus (HCV) NS3 protease complexed with NS4A cofactor peptide. This hexapeptide corresponds to the N-terminal cleavage product of an HCV dodecapeptide substrate derived from the NS5A/5B cleavage site. Structure-activity studies on Ac-DDIVPC-OH revealed that side chains of the P4, P3 and P1 residues contribute the most to binding and that the introduction of a D-amino acid at the P5 position improves potency considerably. Furthermore, there is a strong preference for cysteine at the P1 position and conservative replacements, such as serine, are not well tolerated.

Amino Acid Sequence↗

Isolation and characterisation of pig Peyer's patch dendritic cells.

We have isolated dendritic cells (DC) from Peyer's patches (PP) of pig small intestine by mechanical tissue disruption followed by fractionation of isolated cells on metrizamide gradients. Characterisation was carried out using the following criteria: morphology; lysosomal enzyme synthesis; expression of membrane antigens; and capacity for antigen presentation. Dendritic cells did not express acid phosphatase or beta-galactosidase, but were weakly positive for non-specific esterase and ATPase. Dendritic cells did not express CD3, CD2, sIg, or an antigen specific for pig mononuclear phagocytes and granulocytes. They did, however, express MHC class II at very high levels. They were shown to be potent stimulators in an allogeneic mixed lymphocyte reaction.

Acid Phosphatase↗

Increased expression of complement component C3 in the plasma of obese Zucker fa and LA/N fa(f) rats compared with their lean counterparts.

OBJECTIVES: The objectives of this study were to determine whether there are differences in the electrophoretic profiles of plasma proteins from lean and obese rats and to identify a protein that was found to be more abundant in the plasma of obese rats. RESEARCH METHODS AND PROCEDURES: Plasma proteins from lean and obese Zucker fa and LA/N fa(f) rats were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The identity of a band that was differentially expressed was determined by amino acid sequencing and Western blot analysis. RESULTS: A band migrating approximately the same distance as the 116 kDa molecular weight marker was more prominent in plasma from obese rats than in plasma of lean rats. Partial sequencing of the peptide revealed that 17 of the first 18 amino acids at the amino terminus were identical with the corresponding residues in the alpha-chain of complement component C3. Western blot analysis confirmed the identity of the peptide as complement component C3. Complement C3 activity was measured using a hemolytic assay to determine whether there was a corresponding increase in the biological activity of this component in the serum of obese rats. Serum from obese rats was found to have 1.8 times as much complement component C3 activity as serum from lean rats. DISCUSSION: Elevated levels of complement C3 in genetically obese rats may be relevant because increased amounts of C3 could serve as a reservoir from which increased amounts of acylation stimulating protein, a cleavage product of complement C3, could be produced.

Amino Acid Sequence↗

Comparative levels of organochlorine compounds in flounders from the northeast coast of Newfoundland and an offshore site.

Muscle tissue of yellowtail flounder, Pleuronectes ferruginea (n = 6) and winter flounder, Pseudopleuronectes americanus (n = 9) collected from Bonavista Bay, Conception Bay and an offshore location off northeastern Newfoundland, Canada, were analyzed for PCBs and other organochlorine compounds to determine if there are geographical variations in the concentrations and patterns of these persistent contaminants. The concentrations of total PCB congeners on a wet weight basis were relatively homogeneous at low ng/g levels. DDE, HCH compounds, and components of technical chlordane were the dominant organochlorine contaminants. Lipid normalized data indicate that PCB concentrations were higher in both species collected in the moderately urbanized region of Conception Bay. Principal Component Analysis (PCA) of PCB congener patterns indicated that flounder collected in Conception Bay had greater proportions of highly chlorinated PCB congeners, which may indicate point-source contamination in this region. Concentrations and patterns of other organochlorine compounds were relatively consistent across all sampling locations.

Animals↗

Hemostasis of punctured blood vessels using high-intensity focused ultrasound.

The hemorrhagic complications of vascular injury can be significant. We report on the use of high-intensity focused ultrasound (HIFU) to stop the hemorrhage of punctured blood vessels in pigs. Two HIFU transducers with frequencies of 3.5 and 2.0 MHz, each equipped with a water-filled conical housing, were used. Major blood vessels (femoral artery and vein, axillary artery, carotid artery and jugular vein), 2-10 mm in diameter, of anesthetized pigs were exposed surgically and punctured with 14- and 18-gauge needles to produce moderate to profuse bleeding. Complete hemostasis was achieved in less than 3 min of HIFU treatment in most blood vessels, and all vessels were patent after the treatment. Both HIFU frequencies were effective in producing hemostasis. Gross examination of the HIFU-treated vessels showed a consistent hardening of the soft tissue surrounding the blood vessels, providing a seal for the puncture hole. Microscopic examination of the vessels showed a remarkably localized HIFU treatment, resulting in coagulation of the adventitia, and an extensive fibrin network around the vessels and in the puncture hole. The vessel walls exhibited focal swelling, without evidence of irreversible injury. HIFU may provide a useful method for achieving hemostasis of punctured and traumatized blood vessels in a variety of clinical settings.

Animals↗

Loss of heterozygosity at microsatellite marker sites for tumour suppressor genes in oesophageal adenocarcinoma.

AIMS: Loss of cell cycle control is an important step in the development of human tumours. A number of tumour suppressor genes are involved in cell cycle control, including p16, p53 and Rb. The aim of this study was to seek evidence of deletions of these genes in oesophageal adenocarcinoma. METHODS: Paired (tumour and normal squamous epithelium) frozen tissue samples from 12 patients were analysed by polymerase chain reaction (PCR) for loss of heterozygosity (LoH) at five microsatellite marker sites (two each for p16 and Rb, one for p53). Aneuploid tumour cell populations were sorted by flow cytometry prior to PCR, to eliminate stromal cell contamination. RESULTS: Of the 12 tumours, 11 (92%) had LoH at one or more loci. LoH at the p53 locus occurred in nine of 12 tumours, at one or both p16 loci in seven of 11 tumours, and at one or both Rb loci in eight of 12 tumours. Five tumours had LoH at two tumour suppressor gene loci, and a further four tumours had LoH at loci for all three genes. CONCLUSIONS: Allelic deletions of p53, p16 and Rb are common in oesophageal adenocarcinoma, and may be important in the development of this disease.

Adenocarcinoma↗

The effects of vasculitis on the gastrointestinal tract and liver.

Vasculitis can affect every organ of the digestive system. In many cases, it may first present with gastrointestinal symptoms. In several forms of vasculitis, including Churg Strauss syndrome, Henoch-Schönlein purpura, and lupus, the majority of patients have gastrointestinal involvement. The astute gastroenterologist should consider vasculitic causes of the symptoms seen in many patients. Making the correct diagnosis requires a thorough understanding of the potential role of vasculitis in causing these symptoms and the appropriate path to making a diagnosis. This article reviews the variety of manifestations of vasculitis on the digestive system, and emphasizes diagnosis and clinical manifestations.

Adrenal Cortex Hormones↗

Novel small renin inhibitors containing 4,5- or 3,5-dihydroxy-2-substituted-6-phenylhexanamide replacements at the P2-P3 sites.

Renin inhibitors containing a 4,5- or a 3,5-dihydroxy-2-substituted-6-phenylhexanamide fragment at the P2-P3 sites have been prepared and evaluated. The four possible diastereomeric diols of the two series of inhibitors were synthesized to determine the optimal configuration of the carbinol centers for these replacements. The most potent inhibitors of each series, la and 2c have a molecular weight of only 503 and IC50 values of 23 and 20 nM in a human plasma renin assay at pH 6.0. Their very low aqueous solubility limited their further evaluation. The efficacy of these P2-P3 replacements is a result of their ability to maintain the important hydrogen-bonds with the enzyme. Due to conformational differences with the dipeptide, adjustment at the P2 side chain was required. These 4,5- and 3,5-dihydroxyhexanamide segments could be seen as novel N-terminal dipeptide replacements.

Amides↗