Search PubMed⌕ Search

Biomedical subjects

J Saunders

Publications and source records attributed to J Saunders.

At least 37 records · Page 2Linked to original sources
PubMed2001

Recent improvements in prediction of protein structure by global optimization of a potential energy function.

Recent improvements of a hierarchical ab initio or de novo approach for predicting both alpha and beta structures of proteins are described. The united-residue energy function used in this procedure includes multibody interactions from a cumulant expansion of the free energy of polypeptide chains, with their relative weights determined by Z-score optimization. The critical initial stage of the hierarchical procedure involves a search of conformational space by the conformational space annealing (CSA) method, followed by optimization of an all-atom model. The procedure was assessed in a recent blind test of protein structure prediction (CASP4). The resulting lowest-energy structures of the target proteins (ranging in size from 70 to 244 residues) agreed with the experimental structures in many respects. The entire experimental structure of a cyclic alpha-helical protein of 70 residues was predicted to within 4.3 A alpha-carbon (C(alpha)) rms deviation (rmsd) whereas, for other alpha-helical proteins, fragments of roughly 60 residues were predicted to within 6.0 A C(alpha) rmsd. Whereas beta structures can now be predicted with the new procedure, the success rate for alpha/beta- and beta-proteins is lower than that for alpha-proteins at present. For the beta portions of alpha/beta structures, the C(alpha) rmsd's are less than 6.0 A for contiguous fragments of 30-40 residues; for one target, three fragments (of length 10, 23, and 28 residues, respectively) formed a compact part of the tertiary structure with a C(alpha) rmsd less than 6.0 A. Overall, these results constitute an important step toward the ab initio prediction of protein structure solely from the amino acid sequence.

Models, Molecular↗
PubMed2001

A PCR-based method for detection of potato pathogen, Helminthosporium solani, in silver scurf infected tuber tissue and soils.

Silver scurf caused by Helminthosporium solani causes significant economic losses in table stock, seed and processing potatoes. Specific polymerase chain reaction (PCR) primers, Hs1F1/Hs2R1, from H. solani were used for the amplification of a 447-bp product from 20 tissue samples and 54 single spore H. solani isolates, from eastern Canada (27 isolates), western Canada (13 isolates) and North Dakota in USA (14 isolates), but not from other potato fungal pathogens. In addition to PCR analysis, all 54 isolates were studied using conventional detection methods, visual disease symptoms and/or colony morphology and microscopic examination of the morphology of conidiophores and conidia. The PCR assay successfully detected H. solani and the PCR results correlated well with assessments based on conventional techniques. The detection of H. solani by PCR (1 day) is rapid and offers an alternative to the time consuming conventional diagnostic techniques (4-5 weeks). Nested PCR assay was necessary for the detection of H. solani in soils and thus can provide a sensitive technique to study the epidemiology of silver scurf in soils.

DNA Primers↗
PubMed2001

Clusters within a general adult population of alcohol abstainers.

BACKGROUND: Our previous study found that alcohol abstainers use acute services more and preventative services less than safe level drinkers. The observed relationships between four categories of alcohol consumption and service use were J-shaped for acute services and inverted J-shaped for preventive services. The aim of this paper was to further investigate these relationships. METHODS: The design was a health and lifestyle survey of 41 000 randomly-sampled adults in SE England. The response rate was 60%. Distinctive subgroups within the alcohol abstainer group were investigated using cluster analysis, based on socio-demographic and health status variables. Odds ratios for services use for the abstainer clusters, and three alcohol consumption groups were estimated from a logistic regression model which included age, social class, ethnic group, employment status, household composition, whether the respondent was a carer, smoking habit, use of private health insurance, and health status. RESULTS: Two clusters were formed for both males and females. Cluster 1 comprised, on average, older, frailer, and more disabled people. Cluster 2 comprised younger, healthier people, a greater proportion of whom belonged to ethnic minority groups. Cluster 2 had similar rates of use of Accident & Emergency, GP, optician, and dental services compared with safe level drinkers. Cluster 1's rates differed from those of both Cluster 2 and safe level drinkers in almost all instances. CONCLUSIONS: The J- and inverted J-shaped relationships between alcohol consumption and service use are partly explained by a subgroup of abstainers who are older, of less good health, and who use hospital, clinic, and domiciliary healthcare services much more than safe level drinkers.

Adult↗
PubMed2001

WHP/ISBRA study on state and trait markers in alcoholism.

This article represents the proceedings of a symposium at the 2000 ISBRA Meeting in Yokohama, Japan. The chair was Boris Tabakoff. The presentations were (1) Overview of the WHO/ISBRA study on state and trait markers in alcoholism, by Boris Tabakoff; (2) Biochemical markers of acute and chronic drinking: Results of the WHO/ISBRA study, by Anders Helander; (3) The impact of country of recruitment and body mass index on biological marker dose-response curves in the WHO/ISBRA Study, by Kate M. Conigrave; (4) Relationship of body water to carbohydrate-deficient transferrin measures, by Larry Martinez; and (5) Platelet adenylyl cyclase activity as a trait marker of alcohol dependence, by Paula L. Hoffman.

Adenylyl Cyclases↗
PubMed2001

The effect of dissociation at encoding on intrusive memories for a stressful film.

The occurrence of memory intrusions after a trauma has been linked to peri-traumatic dissociation. In this study, we attempted to induce dissociation experimentally and investigate the impact on intrusive memories. A total of 39 undergraduates were randomly assigned to watch a stressful film under standard conditions or under a dual-task condition in which they simultaneously performed a tapping task. They rated their distress post-film and again after 2 weeks, and kept a diary of intrusive memories. Contrary to prediction, there were no differences in levels of distress or explicit memory between the two conditions, and the dual-task condition was followed by significantly fewer memory intrusions. Dual-task conditions may not provide a good analogue to naturally occurring dissociation. The possible preventive effects of the tapping task are discussed in terms of the dual-representation theory of post-traumatic stress disorder.

Adaptation, Psychological↗
PubMed2000

Cell-mediated immune response in calves to single-dose, trickle, and challenge infections with Fasciola hepatica.

A peripheral blood mononuclear cell (PBMC) proliferation assay was used to study the cell-mediated immune response in eight calves experimentally infected with Fasciola hepatica. Hypersensitivity-related eosinophil and mast-cell responses were also assessed. The primary infection of 500 metacercariae was administered either as a single-dose or as a trickle infection over a 4-week period. Calves were challenge-infected 4 months later with 100 metacercariae and slaughtered 24 weeks postprimary infection. Skin eosinophil counts (SEC) were determined prior to infection on the basis of the intradermal reaction (IDR) to phytohaemagglutinin (PHA). These counts correlated negatively with the mean fluke length but not with the fluke burden found at necropsy. At the end of the experiment, non-specific (PHA) and specific (excretory-secretory parasite, products, FhESAg, and whole-worm extract, FhSomAg) immediate type hypersensitivity IDR were elicited in contrast to delayed type hypersensitivity (DTH) responses. The SEC correlated with blood eosinophilia but not with parasite parameters. These findings suggest that the eosinophil response does not correlate clearly with the development of resistance to F. hepatica infection in cattle. A specific mononuclear cell response to FhSomAg was detectable as early as 7 days after infection in both infected groups, being significantly higher during the very early migratory phase of the juveniles in the single-dose infected calves than in the trickle infected calves. This response remained significantly higher in infected groups than in the control group throughout the experiment. Challenge elicited a significant proliferative response, less pronounced than after primary infection. No production of gamma-interferon (INF-gamma) was recorded 3 weeks after challenge. At necropsy, the mean number of flukes recovered was similar in both infected groups, suggesting that the rate at which the infection is administrated has no effect on protective immunity. Hepatic lesions, similar in both infected groups, were characterised by marked eosinophil and mast-cell infiltration. Liver biopsies were performed and their diagnostic value is discussed. All results suggest that F. hepatica infection predominantly induces a Type-2 response in cattle, and that this response has little protective effect.

Animals↗
PubMed2000

Serial fetal lung volume measurement using three-dimensional ultrasound.

OBJECTIVE: To establish reference intervals for fetal lung growth. DESIGN: Longitudinal observational study. SUBJECTS: Fifty-eight women with initially uncomplicated singleton pregnancies were recruited from the antenatal population of a teaching hospital. Four women were excluded from the final analysis because of complications arising in their pregnancy. METHODS: Each subject was serially scanned at monthly intervals. At each visit lung volume was measured using an ultrasound-based computerized three-dimensional imaging system. Multilevel models were used to determine conditional and unconditional reference intervals. RESULTS: Reference intervals for fetal lung growth were derived. Fetal lung volume increases in a non-linear way with gestation. CONCLUSIONS: Our computerized system has the capacity to be used in conjunction with any standard two-dimensional ultrasound scanner in order to measure volume. Lung volume measurement may be useful in predicting pulmonary hypoplasia.

Adult↗
PubMed2000

MRI guided percutaneous abdominal biopsy in a closed magnet: assessment in an animal study.

MRI guided percutaneous abdominal biopsy was evaluated in an animal model, using a closed magnet and different types of needles. Thirty-six single pass biopsies were performed in 6 piglets with 6 types of MR compatible needles. Virtual targets of a diameter of 2 cm were drawn on the images of the right and left lobe of the liver and the upper and lower poles of both kidneys. FMPSPGR sequences were applied during an apnea of 19 to 23 seconds in axial, sagittal, coronal or axial oblique planes using a closed 1.0 T magnet and the body coil. Piglets were autopsied 1 hour after the procedure. Mean duration of the procedure was 16.9 (11-37) minutes; mean number of acquisitions per procedure was 5.9 (3-12); mean number of redirections of the needle was 0.6 (0-4). Pathological samples from the liver and kidneys of good quality were obtained in 22/36 (72.2%) cases. A subcapsular hematoma was observed in 18/24 (75.0%) cases of renal biopsies and in 1/12 (8.3%) of hepatic biopsies. No statistically significant correlation could be established between duration of the procedure and site of biopsy and between the type of biopsy needle and complication (p = 0.18 to 0.85). In conclusion, MRI guided percutaneous needle biopsy in the abdomen is a reliable technique in piglets using a closed magnet.

Abdomen↗
PubMed1999

Nonpeptidic HIV protease inhibitors: 6-alkyl-5,6-dihydropyran-2-ones possessing a novel and achiral 3-(2-t-butyl-5-methyl-4-sulfamate)phenylthio moiety.

Dihydropyran-2-ones possessing a sulfamate moiety at the 4-position of the thiophenyl ring were designed to reach S3' pocket of the HIV protease. Synthetic routes for the preparation of thiotosylates possessing 3-(2-t-butyl-5-methyl-4-sulfamate) phenylthio moiety were established. SAR of various sulfamate analogs including HIV protease binding affinities, antiviral activities and therapeutic indices will be described.

Animals↗
PubMed1999

Nonpeptidic HIV protease inhibitors: 6-alkyl-5,6-dihydropyran-2-ones possessing achiral 3-(4-amino/carboxamide-2-t-butyl,5-methylphenyl thio) moiety: antiviral activities and pharmacokinetic properties.

Dihydropyran-2-ones possessing amino and carboxamide functionalities on 3-SPh (2-tert-butyl, 5-methyl) ring were synthesized and evaluated for their antiviral activities. Both the enantiomers of inhibitor 15 were synthesized. The in vitro resistance profile, inhibitory activities against cytochrome P450 isozymes and pharmacokinetic properties of inhibitor 15S will be discussed.

Animals↗
PubMed1999

Opportunities for novel therapeutic agents acting at chemokine receptors.

Chemokines are proinflammatory mediators that primarily control leukocyte migration into selected tissues and upregulation of adhesion receptors. They also have a role in pathological conditions that require neovascularization and are implicated in the suppression of viral replication. By interaction with their respective G-protein-coupled receptor, chemokines have a profound influence over the selective recruitment of specific cell types in acute inflammatory disease and, hence, inhibition of their action should be of therapeutic benefit. Only now are small molecule inhibitors becoming available to validate this speculation. In this review, without seeking to be comprehensive, the authors provide an introduction to chemokines, their receptors and their role in certain disease processes. Also, recent disclosures claiming novel nonpeptide ligands for chemokine receptors are summarized.

Journal Article↗
PubMed1999

A mobile high-field magnetic resonance system for neurosurgery.

OBJECT: The authors' goal was to place a mobile, 1.5-tesla magnetic resonance (MR) imaging system into a neurosurgical operating room without adversely affecting established neurosurgical management. The system would help to plan accurate surgical corridors, confirm the accomplishment of operative objectives, and detect acute complications such as hemorrhage or ischemia. METHODS: The authors used an actively shielded 1.5-tesla magnet, together with 15 mtesla/m gradients, MR console computers, gradient amplifiers, a titanium, hydraulic-controlled operating table, and a radiofrequency coil that can be disassembled. The magnet is moved to and from the surgical field by using overhead crane technology. To date, the system has provided unfettered access in 46 neurosurgical patients. In all patients, high-definition T1- and/or T2-weighted images were rapidly and reproducibly acquired at various stages of the surgical procedures. Eleven patients underwent craniotomy that was optimized after preincision imaging. In four patients who harbored subtotally resected tumor, intraoperative MR imaging aided the surgeon in removing the remaining tumor. Interestingly, the intraoperative administration of gadolinium demonstrated a dynamic expansion of enhancement beyond the preoperative contrast contour in patients with malignant glioma. These zones of new enhancement proved, on examination of biopsy samples, to be tumor. CONCLUSIONS: The authors have demonstrated that high-quality MR images can be obtained in the operating room within reasonable time constraints. Procedures can be conducted without compromising or altering traditional neurosurgical, nursing, or anesthetic techniques. It is feasible that within the next decade intraoperative MR imaging may become the standard of care in neurosurgery.

Adult↗
PubMed1998

Transmission disequilibrium as a test of linkage and association between HLA alleles and pauciarticular-onset juvenile rheumatoid arthritis.

OBJECTIVE: To determine if HLA class I and II alleles previously found to be associated with (or protective against) pauciarticular-onset juvenile rheumatoid arthritis (pauci-onset JRA) in population-association studies are transmitted from heterozygous parents to an extent different from the expected 50%. METHODS: One hundred one Caucasian North American families that had a child with pauci-onset JRA and at least 1 parent who was heterozygous for the allele of interest were available for analysis. Both biologic parents and all children (affected and unaffected) were typed for HLA class I and II alleles. The transmission disequilibrium test (TDT) was used to determine if affected offspring received the disease-associated (or protective) allele more (or less) frequently than its alternate allele. In families in which an unaffected sibling was available, the unmatched chi-square test was used to determine if a meiotic segregation distortion bias existed. RESULTS: HLA class I alleles A2, B27, and B35 showed a significantly higher than expected frequency of transmission to affected offspring, as did class II alleles DR5 and DR8. HLA-DR4 was found to be transmitted significantly less frequently than expected to affected, but not unaffected, offspring. All alleles that showed an excess transmission to affected offspring were transmitted to unaffected offspring at expected rates. When the data were stratified by age and sex, the likelihood of transmission of some of the alleles was strongly influenced by these variables. For example, excess transmission of HLA-DR5 was found exclusively in female patients who were younger at the time of disease onset. CONCLUSION: Results from these family-based studies rule out the possibility that HLA disease associations found in earlier studies were a result of population stratification and establish linkage and association between the major histocompatibility complex and pauci-onset JRA.

Adolescent↗