Biomedical subjects

B Yu

Publications and source records attributed to B Yu.

At least 163 records · Page 9Linked to original sources

PubMed1996

Multisection T1-weighted hybrid-RARE: a pulse sequence for MR imaging of the entire liver during suspended respiration.

It is shown that the maximum average-data-collection-speed (ADCS) of multisection 2D hybrid-RARE sequences is independent of TR and TEeff, and a monotonically increasing function of echo-train-length (ETL). This result was used in the design of an optimized T1-weighted hybrid-RARE sequence that produces 20 images of the abdomen in 31 s divided into four breath-hold periods. The resulting ADCS is 58 lines in k-space per second. Twenty-four subjects (2 healthy volunteers and 22 patients) were imaged with a protocol that also included: (a) breath-hold T1-weighted FLASH which acquires data at 34 lines in k-space per second (49 s scan time), and (b) T1-weighted conventional spin-echo (9:44 minutes scan time) with respiratory compensation. The experiments show that this T1-weighted-hybrid-RARE sequence has: (1) a level of T1 weighting that is comparable with the conventional sequences, (2) very low vulnerability to susceptibility artifacts, (3) high data acquisition efficiency, and (4) higher SNR than T1-weighted-FLASH. In conclusion, the T1-weighted-hybrid-RARE sequence described herein is an efficacious and reproducible technique for rapid imaging of the upper abdomen during suspended respiration.

Adult↗

PubMed1996

Optimum phase ratio in the triple jump.

The purpose of this study was to develop and validate a method to determine the optimum phase ratio that yields the longest actual distance for a given triple jumper. Two hypotheses were tested: (a) for any given triple jumper, the greater the gain in the vertical velocity the greater the loss in the horizontal velocity; and (b) there is no single optimum phase ratio for all triple jumpers. Kinematic data were collected for four elite male triple jumpers. It was found that the loss in the horizontal velocity during a support phase has a significant positive linear correlation with the gain in the vertical velocity during the same support phase. The slope of the regression line was referred to as the horizontal-to-vertical velocity conversion factor. Based on this relationship, an optimization model for the longest actual distance was developed to determine the optimum phase ratio for each of the four subjects. The optimization results showed that there was an optimum phase ratio for the longest actual distance for each triple jumper. The results of a validity test showed that the model predicted the actual distance with a degree of fair accuracy. The results of sensitivity analysis showed that the optimum phase ratio for a given athlete was a function of the horizontal-to-vertical velocity conversion factor and the horizontal velocity at the touchdown of the hop. These results support the two hypotheses of this study.

Humans↗

PubMed1996

Structure-based design of achiral, nonpeptidic hydroxybenzamide as a novel P2/P2' replacement for the symmetry-based HIV protease inhibitors.

A combination of structure-activity studies, kinetic analysis, X-ray crystallographic analysis, and modeling were employed in the design of a novel series of HIV-1 protease (HIV PR) inhibitors. The crystal structure of a complex of HIV PR with SRSS-2,5-bis[N-(tert-butyloxycarbonyl)amino]-3,4-dihydroxy-1, 6-diphenylhexane (1) delineated a crucial water-mediated hydrogen bond between the tert-butyloxy group of the inhibitor and the amide hydrogen of Asp29 of the enzyme. Achiral, nonpeptidic 2-hydroxyphenylacetamide and 3-hydroxybenzamide groups were modeled as novel P2/P2' ligands to replace the crystallographic water molecules and to provide direct interactions with the NH groups of the Asp29/129 residues. Indeed, the symmetry-based inhibitors 7 and 19, possessing 3-hydroxy and 3-aminobenzamide, respectively, as a P2/P2' ligand, were potent inhibitors of HIV PR. The benzamides were superior in potency to the phenylacetamides and have four fewer rotatable bonds. An X-ray crystal structure of the HIV PR/7 complex at 2.1 A resolution revealed an asymmetric mode of binding, in which the 3-hydroxy group of the benzamide ring makes the predicted interaction with the backbone NH of Asp29 on one side of the active site only. An unexpected hydrogen bond with the Gly148 carbonyl group, resulting from rotation of the aromatic ring out of the amide plane, was observed on the other side. The inhibitory potencies of the benzamide compounds were found to be sensitive to the nature and position of substituents on the benzamide ring, and can be rationalized on the basis of the structure of the HIV PR/7 complex. These results partly confirm our initial hypothesis and suggest that optimal inhibitor designs should satisfy a requirement for providing polar interactions with Asp29 NH, and should minimize the conformational entropy loss on binding by reducing the number of freely rotatable bonds in inhibitors.

Benzamides↗

PubMed1996

DNA testing in familial hypertrophic cardiomyopathy: clinical and laboratory implications.

Counselling and clinical assessment in familial hypertrophic cardiomyopathy (FHC) is difficult, particularly in the young, since echocardiographic and ECG changes may not be diagnostic and clinical severity can vary. From 1990, when the beta-cardiac myosin heavy chain gene was implicated in the aetiology of FHC, considerable information about the molecular genetics of this disorder has emerged. However, an important question facing health professionals is the practical significance of DNA testing in FHC. The present study describes a DNA-based approach to screening for five commonly reported mutations involving the beta-cardiac myosin heavy chain gene. Approximately 11% of randomly selected families had an abnormality detected.

Cardiomyopathy, Hypertrophic↗

PubMed1996

Sex-role attitudes and clinical appraisal in psychiatry residents.

OBJECTIVE: To measure sex-role beliefs of psychiatry residents and to examine bias in clinical appraisal. METHOD: Residents (45 female, 51 male) evaluated 1 of 4 possible clinical case histories-a female or male patient with histrionic personality disorder (HPD) or antisocial personality disorder (APD)-and completed the Sex-Role Egalitarianism Scale (SRES). RESULTS: As predicted, female residents were more egalitarian than male residents (P < 0.03) according to the SRES. As expected, significantly more male than female patients received the diagnosis of APD (P < 0.00002). Although it was predicted that female patients would more often be given the HPD diagnosis than males, no significant gender differences were found. Sex of resident was not found to influence clinical behaviour significantly. CONCLUSIONS: These results highlight differential sex-role attitudes, as measured by the SRES, between female and male residents and suggest that residents' sex-role biases affect the diagnosis of APD. These results have implications for psychiatric assessment and treatment. Further understanding of these issues is critical to the development of educational tools to address sex biases in psychiatry.

Adult↗

PubMed1996

Phase I trial of iodine 131-labeled COL-1 in patients with gastrointestinal malignancies: influence of serum carcinoembryonic antigen and tumor bulk on pharmacokinetics.

PURPOSE: COL-1 is a high-affinity murine monoclonal antibody (MAb) specific for carcinoembryonic antigen (CEA). A phase I trial was conducted in which a uniform quantity of antibody labeled with escalating doses of iodine 131 (131I) was administered to patients with advanced gastrointestinal (GI) malignancies to evaluate tolerance and pharmacokinetics. PATIENTS AND METHODS: Eighteen patients with advanced, assessable GI malignancies (16 colon, one pancreas, and one gastric) previously treated with conventional chemotherapy (but no pelvic radiation) received 20 mg of COL-1 labeled with 131I, with doses from 10 mCi/m2 to 75 mCi/m2. In this cohort, the baseline serum CEA level ranged from 6 to 2,739 ng/mL (mean +/- SD, 500 +/- 639). RESULTS: Nuclear imaging detected at least one tumor site in all 18 patients; 82% of all tumor involved organs were positive and 58% of all lesions > or = 1.0 cm were detected. Immune complexes were detected in 89% of patients 5 minutes after completion of infusion, and levels correlated with CEA levels (r = .71). Elevated CEA (> 500 ng/mL) and tumor bulk (total tumor area > 150 cm2) correlated directly with clearance of serum radioactivity and inversely with serum half-life and cumulative serum radioactivity parameters. Nonhematologic toxicity was mild and non-dose-limiting. Hematologic toxicity, particularly thrombocytopenia, was both dose-related and dose-limiting. The maximal-tolerated dose is 65 mCi/m2. The correlation between dose (millicuries per square meter) and thrombocytopenia was made stronger, by accounting for either variation in pharmacokinetics, or variation in serum CEA and tumor bulk. CONCLUSION: 131I-COL-1 is well tolerated, except for hematologic toxicity. These data suggest that patients with highly elevated circulating CEA levels and/or increased tumor bulk may clear 131I-labeled COL-1 more rapidly from the circulation and experience less myelosuppression.

Antibodies, Monoclonal↗

PubMed1996

Effects of crude fibre level in the diet on the intestinal morphology of growing rabbits.

The experiment was conducted to study the effects of 5.5, 8.5, 11.5 and 14.5% dietary fibre levels on growth performance and intestinal villi in growing rabbits. After the 5-week feeding period, food intake and body weight gain increased with increasing dietary fibre levels, feed conversion was highest with 11.5% dietary fibre. Scanning electron microscopy showed slight changes to the jejunal villi and the caecal mucosa in rabbits fed high dietary fibre (14.5%), but the degree of damage was greater in the caecum than the jejunum. Flattened colon villi were seen in the low dietary fibre group whereas high levels showed no effect.

Animals↗

PubMed1996

[Influences of early enteral feeding enriched with glutamine on the gut blood flow and oxygen consumption in severely burned mini-swines].

In order to investigate the effects of L-glutamine on the gut blood flow and oxygen consumption after burn, 14 mini-swines were randomly and equally divided into Non-Gln group and Gln group (which was supplied with L-glutamine, 0.64 g/kg day). Gut blood flow and oxygen consumption were continuously determined from preburn to PBD 10. The results showed that portal venous blood flow (Fpv) and oxygen consumption decreased markedly in all animals, especially the Non-Gln group (P < 0.01), on PBD 4 to PBD 10, when Fpv and oxygen consumption returned to preburn level in Gln group and remained low in Non-Gln group. The portal venous MDA concentration was significantly higher in Non-Gln group than that of Gln group. The results suggest that early enteral feeding enriched with glutamine increases the intestinal blood flow, and decreases the intestinal hypoxemia and reperfusion injury.

Animals↗

PubMed1996

Calibration of measured center of pressure of a new stairway design for kinetic analysis of stair climbing.

A stairway that allows the collection of kinetic data is essential for biomechanical studies on stair climbing. There is a need to validate the measured center of pressure (COP) on the surface of a stair in order to verify the accuracy of the calculation of joint kinetics. The purpose of this study was to validate a new stairway design for kinetic analysis of stair climbing through a calibration and error analysis of the COP obtained from this system. The new stairway design allows the collection of kinetic data for multiple steps without any constraint to foot placement. Known vertical forces were applied to known locations on the surface of each stair and each force plate. Multiple regression analyses were conducted to determine the distribution pattern of the error in the measured COP. It was found that the error in the COP was a function of location on the stair or force plate. The magnitude of the vertical force had no significant effect on the error in the measured COP. The distribution pattern of the error in the measured COP on the force plates used in this study matched the results in the literature. A healthy female subject was used as a subject in a stair climbing test. The error in the measured COP had a significant effect on the calculated joint resultant moments, especially the abduction-adduction and internal-external rotation moment. The correction of these errors should make the kinetic calculation in stair climbing more accurate.

Adult↗

PubMed1996

[Enhancement of gut immune function by early enteral feeding enriched with L-glutamine in severe burned miniswines].

In order to investigate the effect of L-glutamine on gut immune function, 14 miniswines with 30% TBSA full thickness burns were randomly and equally divided into NON-GLN group and GLN group. GLN group animals were supplied with L-glutamine 0.64 g/day, and NON-GLN group received equal amount of non-glutamine amino acids. The S-IgA concentration of jejunal and IgA concentration of arterial blood were determined on PBD (post burn day) 1, 4, 7, 10. S-IgA concentration of ileal contents was measured on PBD10. The results showed that the concentrations of S-IgA in the jejunal and ileal contents as well as IgA in arterial blood decreased significantly after burns in NON-GLN group. L-glutamine supplement increased the excretion of S-IgA of intestinal mucosa in the GLN group. This result suggests that oral feeding of L-glutamine improves the intestinal S-IgA excretion after burns efficiently, and it plays an important role in the prevention of endotoxin and bacterial translocation after burns.

Animals↗

PubMed1996

[The mechanisms of ET-1-induced lung edema].

OBJECTIVE: To investigate the machanisms of ET-1-induced lung edema. METHODS: Different doses of ET-1 were added to isolate rat lungs perfused by Ringer's solution containing albumin to explore the mechanisms of ET-1 induced pulmonary edema. The lung weight gain, pulmonary vascular permeability to water (Wf) and albumin (Ps) were observed. RESULTS: It was found that low dose ET-1 increased lung weight gain, pulmonary artery pressure, pulmonary capillary pressure, pulmonary vascular post-resistance and total resistance, but no significant changes of vascular permeability were observed. CONCLUSION: The mechanisms of lung edema induced by ET-1 are different. Low dose ET-1 may induce lung edema by increasing pulmonary vascular permeability while large dose ET-1 by increasing pulmonary vascular pressure.

Animals↗

PubMed1996

[The relationship between selenium and immunity in large bowel cancer].

44 patients with large bowel cancer were randomly divided into two groups, therapeutic and control group. The level of serum selenium, T lymphocyte subsets consisted of CD3, CD4, CD8, CD4/ CD8, NK and LAK cell activity were measured preoperation and postoperation. Simultaneously se content in tumor and normal tissue of the large bowel were measured in 35 cases. Serum se level (0.81 +/- 0.14 umol/L) was lowered in patients with large bowel cancer and increased significantly after se supplementation in the therapeutic group (P < 0.01). It was significantly different from that of the control group (P < 0.01), CD3, CD4, CD4/CD8, NK and LAK cell activity were obviously increased postoperatively in the therapeutic group and significantly different from those of the control group. The results suggest that supplement of Se can promote cell-mediated immunity in humans. In addition, Se can promote cell-mediated immunity in humans. The Se level of 22. 13 +/- 1.76 umol/g in tumor was significantly lower than that of 24.30 +/- 1.96 umol/g in normalmucosa in case of large bowel cancer (P < 0.01). This indicates that there may be a close relationship between low se level and the carcinogenesis of the colon and rectum.

Adult↗

PubMed1996

[Effect of L-glutamine on the gut glucose metabolism in severe burned miniswines].

In order to investigate the effect of L-glutamine on gut glucose metabolism, 14 miniswines with 30% TBSA full thickness burns were used in this study. The results showed that: the Nonglutamine group exhibited a decreased gut glucose utilization, and glutamine-group showed a small amount of gut glucose net release (0.11 mumol.min-1.kg-1), and from post burn day 4 on, both groups showed net gut glucose release, but glutamine-group had higher net gut glucoses than that of nonglutamine group (P < 0.01). This result suggests that administration of glutamine decreases gut glucose utilization and increases gut glucose synthesis significantly after severe burns.

Animals↗

PubMed1995

Structural basis for major histocompatibility complex (MHC)-linked susceptibility to autoimmunity: charged residues of a single MHC binding pocket confer selective presentation of self-peptides in pemphigus vulgaris.

Human T-cell-mediated autoimmune diseases are genetically linked to particular alleles of MHC class II genes. Susceptibility to pemphigus vulgaris (PV), an autoimmune disease of the skin, is linked to a rare subtype of HLA-DR4 (DRB1*0402, 1 of 22 known DR4 subtypes). The PV-linked DR4 subtype differs from a rheumatoid arthritis-associated DR4 subtype (DRB1*0404) only at three residues (DR beta 67, 70, and 71). The disease is caused by autoantibodies against desmoglein 3 (DG), and T cells are thought to trigger the autoantibody production against this keratinocyte adhesion molecule. Based on the DRB1*0402 binding motif, seven candidate peptides of the DG autoantigen were identified. T cells from four PV patients with active disease responded to one of these DG peptides (residues 190-204); two patients also responded to DG-(206-220). T-cell clones specific for DG-(190-204) secreted high levels of interleukins 4 and 10, indicating that they may be important in triggering the production of DG-specific autoantibodies. The DG-(190-204) peptide was presented by the disease-linked DRB1*0402 molecule but not by other DR4 subtypes. Site-directed mutagenesis of DRB1*0402 demonstrated that selective presentation of DG-(190-204), which carries a positive charge at the P4 position, was due to the negatively charged residues of the P4 pocket (DR beta 70 and 71). DR beta 71 has a negative charge in DRB1*0402 but a positive charge in other DR4 subtypes, including the DR4 subtypes linked to rheumatoid arthritis. The charge of the P4 pocket in the DR4 peptide binding site therefore appears to be a critical determinant of MHC-linked susceptibility to PV and rheumatoid arthritis.

Amino Acid Sequence↗

PubMed1995

Kinetic characterization and cross-resistance patterns of HIV-1 protease mutants selected under drug pressure.

Eleven different recombinant, drug-resistant HIV-1 protease (HIV PR) mutants--R8Q, V32I, M46I, V82A, V82F, V82I, I84V, V32I/I84V, M46I/V82F, M46I/I84V, and V32I/K45I/F53L/A71V/I84V/L89M--were generated on the basis of results of in vitro selection experiments using the inhibitors A-77003, A-84538, and KNI-272. Kinetic parameters of mutant and wild-type (WT) enzymes were measured along with inhibition constants (Ki) toward the inhibitors A-77003, A-84538, KNI-272, L-735,524, and Ro31-8959. The catalytic efficiency, kcat/Km, for the mutants decreased relative to WT by a factor of 1.2-14.8 and was mainly due to the elevation of Km. The effects of specific mutations on Ki values were unique with respect to both inhibitor and mutant enzyme. A new property, termed vitality, defined as the ratio (Kikcat/Km)mutant/(Kikcat/Km)WT was introduced to compare the selective advantage of different mutants in the presence of a given inhibitor. High vitality values were generally observed with mutations that emerged during in vitro selection studies. The kinetic model along with the panel of mutants described here should be useful for evaluating and predicting patterns of resistance for HIV PR inhibitors and may aid in the selection of inhibitor combinations to combat drug resistance.

Amino Acid Sequence↗

PubMed1995

Signal transduction pathways leading to arachidonic acid release from neutrophilic HL-60 cells. The involvement of G protein, protein kinase C and phospholipase A2.

Arachidonic acid release from undifferentiated and neutrophilic HL-60 cells was studied. In neutrophilic cells it was stimulated by N-formyl-Met-Leu-Phe and mastoparan by a mechanism involving Gi protein and phospholipase C and was largely dependent on diacyglycerol lipase. Maximum release from both cell types was achieved with fluoride and required cellular energy. Inhibitor studies suggest that arachidonic acid release by fluoride stimulation leads to phospholipase A2 activation with signal transduction involving phospholipase C and protein kinase C. Only neutrophilic cells responded to phorbol ester if Ca(2+)-ionophore was simultaneously present but this effect was abolished by extended treatment with phorbol ester. Thus, protein kinase C plays a major role in highly stimulated neutrophilic cells. These cells are differently equipped with protein kinase C isoenzymes compared with undifferentiated cells. In contrast, both cell types contain similar levels of type II and cytosolic phospholipases A2, the former being by far the more prevalent.

Arachidonic Acid↗

PubMed1995

Critical characteristics of technique in throwing the discus.

The purpose of this study was to identify those characteristics of the techniques used by elite discus throwers that are most closely related to the distances they record. The subjects were the competitors in the discus throw events at two major meetings. Two S-VHS video cameras were used to record the performances of the subjects; the direct linear transformation (DLT) procedure was used to obtain three-dimensional data from these records. For the males, the change in speed of the discus during the second double support phase was more influential than the change in speed during any other phase in accounting for differences in the distances of the throws recorded. For the females, the changes in speed during the flight phase and during the second double support phase were about equally influential in accounting for differences in the distance thrown. The findings suggest that emphasis placed on achieving a large change in the speed of the discus during the second double support phase is well founded; that the speed of release is the most influential determinant of the distance of the throw; and that, in most cases, the aerodynamic forces exerted on the discus during the flight increase the distance of the throw.

Acceleration↗

PubMed1995

Carbapenem antibiotic production in Erwinia carotovora is regulated by CarR, a homologue of the LuxR transcriptional activator.

Strain GS101 of Erwinia carotovora makes the carbapenem antibiotic, 1-carbapen-2-em-3-carboxylic acid. Mutants defective in antibiotic production can be assigned to two groups, group 1 and group 2. Group 2 mutants are defective in the carl gene encoding a protein responsible for synthesis of the Lux autoinducer N-(3-oxohexanoyl)-L-homoserine lactone (OHHL), which is required to induce carbapenem synthesis in strain GS101. In this paper we describe the molecular genetic analysis of the group 1 mutants which we presumed were defective in the carbapenem biosynthesis (car) genes. We isolated a cosmid (cWU142) that complemented the group 1 mutants of strain GS101. A small (1.03 kb) subclone of cWU142 complemented most of the group 1 mutants, and the sequence revealed that the relevant gene (carR) encodes a homologue of the Vibrio fischeri LuxR protein. A disproportionately high frequency of carR mutants arose in strain GS101 and this was due to carR acting as a 'hot spot' target for secondary transposition of a Tn5 element in this strain. The CarR protein joins a rapidly growing list of homologues, found in taxonomically unrelated bacteria, which act as positive transcriptional activators of genes encoding diverse metabolic functions, including bioluminescence, exoenzyme virulence factor synthesis, cell division, plasmid conjugation, rhizosphere-specific gene induction, surfactant synthesis and antibiotic production. Most of these LuxR-type regulators have been shown to depend, for their function, on N-acyl homoserine lactones, which act as chemical signals enabling co-ordination of gene expression with cell density.

Amino Acid Sequence↗