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Biomedical subjects

Y Yan

Publications and source records attributed to Y Yan.

At least 91 records · Page 5Linked to original sources
PubMed2000

Primary treatment choices for men with clinically localized prostate carcinoma detected by screening.

BACKGROUND: Increasingly, prostate carcinoma is diagnosed through screening. However, little is known regarding factors that influence a patient's decision concerning the treatment choices presented to him. METHODS: Subjects were prostate carcinoma patients detected through the Washington University PSA Prostate Cancer Screening Program between September 1989 and June 1998. The sources of data were the prostate specific antigen (PSA) screening database and follow-up questionnaire. RESULTS: Among 1809 study subjects, 79.2% chose radical prostatectomy (RP), 12.4% chose radiation therapy, and 8.4% chose watchful waiting (WW) as their decision regarding primary treatment. In bivariate analyses, education, income, age, indication for prostate biopsy, comorbidity score, serum PSA level, clinical stage, and pretreatment urinary and sexual function were associated significantly with treatment choice, but race, marital status, and Gleason grade were not. In a multivariate analysis, age, race, clinical stage, PSA level, and pretreatment urinary and sexual function were found to be associated significantly with treatment choice. For every 5-year decrease in age, the odds for choosing RP versus WW increased by 276%; for every 1-ng increase in PSA, the odds for choosing RP versus WW increased by 12%. Non-African-American patients were greater than four times more likely to select RP versus WW. Patients with T2 tumors and those with normal pretreatment urinary function were three times more likely and twice more likely to choose RP versus WW, respectively. CONCLUSIONS: In the current study, RP was the most widely used treatment in patients with screen-detected prostate carcinoma. Age, race, PSA level, clinical stage, and pretreatment urinary and sexual function were significant factors influencing treatment selection.

Aged↗
PubMed2000

X-ray structure of simian immunodeficiency virus integrase containing the core and C-terminal domain (residues 50-293)--an initial glance of the viral DNA binding platform.

The crystal structure of simian immunodeficiency virus (SIV) integrase that contains in a single polypeptide the core and the C-terminal deoxyoligonucleotide binding domain has been determined at 3 A resolution with an R-value of 0.203 in the space group P2(1)2(1)2(1). Four integrase core domains and one C-terminal domain are found to be well defined in the asymmetric unit. The segment extending from residues 114 to 121 assumes the same position as seen in the integrase core domain of avian sarcoma virus as well as human immunodeficiency virus type-1 (HIV-1) crystallized in the absence of sodium cacodylate. The flexible loop in the active site, composed of residues 141-151, remains incompletely defined, but the location of the essential Glu152 residue is unambiguous. The residues from 210-218 that link the core and C-terminal domains can be traced as an extension from the core with a short gap at residues 214-215. The C(alpha) folding of the C-terminal domain is similar to the solution structure of this domain from HIV-1 integrase. However, the dimeric form seen in the NMR structure cannot exist as related by the non-crystallographic symmetry in the SIV integrase crystal. The two flexible loops of the C-terminal domain, residues 228-236 and residues 244-249, are much better fixed in the crystal structure than in the NMR structure with the former in the immediate vicinity of the flexible loop of the core domain. The interface between the two domains encompasses a solvent-exclusion area of 1500 A(2). Residues from both domains purportedly involved in DNA binding are narrowly distributed on the same face of the molecule. They include Asp64, Asp116, Glu152 and Lys159 from the core and Arg231, Leu234, Arg262, Arg263 and Lys264 from the C-terminal domain. A model for DNA binding is proposed to bridge the two domains by tethering the 228-236 loop of the C-terminal domain and the flexible loop of the core.

Amino Acid Sequence↗
PubMed2000

Rosiglitazone short-term monotherapy lowers fasting and post-prandial glucose in patients with type II diabetes.

AIMS/HYPOTHESIS: The short-term efficacy, safety and tolerability of rosiglitazone were compared with placebo in patients with Type II (non-insulin-dependent) diabetes mellitus in a dose-ranging study. METHODS: After a 2-week placebo run-in phase, 303 patients were randomly assigned to 8 weeks of treatment with twice-daily placebo or 2, 4 or 6 mg of rosiglitazone. RESULTS: All rosiglitazone doses significantly reduced fasting plasma glucose compared with baseline. All rosiglitazone treatment groups showed significantly reduced peak postprandial glucose concentrations compared with baseline (p < 0.001) and with placebo (p < 0.0001) and reduced postprandial glucose excursion, without an increase in the area under the postprandial insulin concentration-time curve. Rosiglitazone at 4 and 6 mg twice daily prevented the increase in HbA1c observed in the placebo group. C peptide and serum insulin concentrations were significantly reduced from baseline in all rosiglitazone treatment groups. In all rosiglitazone treatment groups, nonesterified fatty acids decreased significantly (p < 0.0001) and triglycerides did not change. Although total LDL and HDL cholesterol increased significantly in the rosiglitazone treatment groups, total cholesterol/HDL ratios did not change significantly. The proportion of patients with one or more adverse event was similar in all four treatment groups. No patient showed evidence of hepatotoxicity. CONCLUSION/INTERPRETATION: Rosiglitazone given twice daily significantly reduced fasting and postprandial glucose concentrations, C peptide, insulin and nonesterified fatty acids in Type II diabetic patients. The glucose-lowering effect of the 4-mg twice-daily dose of rosiglitazone was similar to that of 6-mg twice daily, suggesting that 4 mg twice daily should be the maximum clinical dose.

Aged↗
PubMed2000

cagA, vacA and iceA virulence genes of Helicobacter pylori isolates of children in Finland.

cagA, vacA s and m genotypes and iceA alleles were analyzed from Helicobacter pylori strains isolated from 17 Finnish children and 32 children of non-Finnish origin living in Finland. Twelve children in the latter group were eastern European and 15 were of African origin. Only three children of non-Finnish origin were born in Finland. The vacA sla subtype was more prevalent in the isolates from Finnish children than African children (76% vs. 7%, P<0.001); vacA s1b frequencies were 5% and 67%, respectively (P<0.001). The iceA1 allele was significantly more prevalent in African than Finnish isolates (93% vs. 35%, P< 0.01). Considerable variation was noted in the frequency of vacA s1 subtypes and iceA alleles in children originating from different geographic regions, but the geographic variation of s1 subtypes resembled that described in other reports.

Antigens, Bacterial↗
PubMed2000

Preoperative quality of life as a predictive factor of 3-year survival after open heart operations.

BACKGROUND: The aim of this prospective study was twofold: to determine the evolution of quality of life in heart surgery patients through the first 3 postoperative years using the Nottingham Health Profile questionnaire and to determine whether preoperative quality of life influences 3-year survival. METHODS: From January to July 1994, 215 patients underwent elective open heart operation in our department. Patients filled in the Nottingham Health Profile questionnaire five times: preoperatively, postoperatively at month 3, and at each anniversary of their operation for 3 years. The evolution of quality of life scores through time were compared using analysis of covariance with repeated measures. Analysis of 3-year survival prognostic factors was achieved using the Cox proportional hazards model. RESULTS: Quality of life scores varied through time, but not significantly. Multivariate analysis showed two independent risk factors to influence 3-year survival: dyspnea class (III-IV versus I-II, relative risk = 2.80, 95% confidence interval = 1.2 to 6.5) and the energy section of the Nottingham Health Profile questionnaire (relative risk = 1.02 by unit, 95% confidence interval = 1.01 to 1.03). CONCLUSIONS: Our study shows quality of life scores to be stable for the first 3 years after operation and the preoperative energy score to be predictive of 3-year survival.

Aged↗
PubMed2000

Intermediate lukewarm (20 degrees c) antegrade intermittent blood cardioplegia compared with cold and warm blood cardioplegia.

BACKGROUND: In the field of intermittent antegrade blood cardioplegia, 3 levels of temperature are commonly used: (1) cold (8 degrees C); (2) tepid (29 degrees C); and (3) warm (37 degrees C). Given the 21 degrees C spread and the metabolic changes that can occur between cold (8 degrees C) and tepid (29 degrees C) cardioplegia, we thought it worthwhile to test a temperature halfway between the cold and tepid levels. The aim of this study was to test the quality of myocardial protection provided by intermediate lukewarm (20 degrees C) cardioplegia by comparing it with cold and warm cardioplegia. Protection was assessed by measuring cardiac troponin I release. METHODS: One hundred thirty-five patients undergoing coronary artery bypass grafting were enrolled in a prospective randomized trial comparing cold (8 degrees C), intermediate lukewarm (20 degrees C), and warm (37 degrees C) antegrade intermittent blood cardioplegia. Cardiac troponin I concentrations were measured in serial venous blood samples. RESULTS: The total amount of cardiac troponin I released was significantly higher in the cold group (4.7 +/- 2.3 microg) than in the intermediate lukewarm (3.4 +/- 2.0 microg) or the warm (3.1 +/- 2.7 microg) groups. The cardiac troponin I concentration was significantly higher at hour 6 in the intermediate lukewarm group (1. 23 +/- 0.55 microg/L) than in the warm group (0.89 +/- 0.50 microg/L). CONCLUSIONS: Intermittent antegrade intermediate lukewarm blood cardioplegia is appropriate and clinically safe. Cardiac troponin I release suggests that intermediate lukewarm cardioplegia is better than cold cardioplegia but less effective than warm cardioplegia in low-risk patients. We therefore recommend the use of warm cardioplegia in low-risk patients.

Aged↗
PubMed2000

Determination of the alkaloid content in different parts of some Mahonia plants by HPCE.

The contents of three quaternary alkaloids (berberine, palmatine, jatrorrhizine) in different parts of the genus Mahonia were determined by high-performance capillary electrophoresis (HPCE). The background electrolyte system composed of 0.1 M phosphate buffer (pH 7.0)-methanol (2:1 V/V) was found to be the most suitable solution for this separation. Brucine was used as internal standard. The linear calibration ranges were 0.004986-0.4986 mg ml-1 (r = 0.9990, n = 5) for berberine, 0.005049-0.5049 mg ml-1 (r = 0.9996, n = 5) for palmatine, and 0.005058-0.5058 mg ml-1 (r = 0.9984, n = 5) for jatrorrhizine. The relative standard deviations were 1.56%, 1.02%, and 1.60% for berberine, palmatine, and jatrorrhizine (n = 6), respectively. The recoveries were determined to be 96.00-101.66% for berberine, 100.15-102.97% for palmatine, and 96.68-102.44% for jatrorrhizine. By using proposed HPCE method, three alkaloids were well-separated within only 5.0 min.

Alkaloids↗
PubMed2000

The flavonoid baicalin exhibits anti-inflammatory activity by binding to chemokines.

Baicalin (BA) is a flavonoid compound purified from the medicinal plant Scutellaria baicalensis Georgi and has been reported to possess anti-inflammatory and anti-viral activities. In order to elucidate the mechanism(s) of action of BA, we tested whether BA could interfere with chemokines or chemokine receptors, which are critical mediators of inflammation and infection. We observed that BA inhibited the binding of a number of chemokines to human leukocytes or cells transfected to express specific chemokine receptors. This was associated with a reduced capacity of the chemokines to induce cell migration. Co-injection of BA with CXC chemokine interleukin-8 (IL-8) into rat skin significantly inhibited IL-8 elicited neutrophil infiltration. BA did not directly compete with chemokines for binding to receptors, but rather acted through its selective binding to chemokine ligands. This conclusion was supported by the fact that BA cross-linked to oxime resin bound chemokines of the CXC (stromal cell-derived factor (SDF)-1alpha, IL-8), CC (macrophage inflammatory protein (MIP)-1beta, monocyte chemotactic protein (MCP)-2), and C (lymphotactin (Ltn)) subfamilies. BA did not interact with CX3C chemokine fractalkine/neurotactin or other cytokines, such as TNF-alpha and IFN-gamma, indicating that its action is selective. These results suggest that one possible anti-inflammatory mechanism of BA is to bind a variety of chemokines and limit their biological function.

Animals↗
PubMed2000

Competing risk adjustment reduces overestimation of opportunistic infection rates in AIDS.

To illustrate the importance of adjusting the estimates of cumulative incidence of acquired immunodeficiency syndrome (AIDS) related illnesses for competing risk of other causes of death, we compared unadjusted and adjusted (for competing events) incidence estimates for four AIDS illnesses: pneumocystis cavinii pneumonia (PCP), mycobacterium avium complex (MAC), cytomegalovirus (CMV), and esophageal candidiases. The study population was patients followed by the Johns Hopkins Hospital AIDS Service between 1989 to 1995. Ratios of 4 year unadjusted incidence estimates to 4 year adjusted incidence estimates for the four diseases ranged from 1.38 to 1.86, corresponding to cumulative death rates of 61% to 69%. For CMV, the ratios of 4 year unadjusted to adjusted incidence estimates for five groups of patients ranged from 1.5 to 2.33, corresponding to cumulative death rates of 48% to 78%. We conclude that ignoring the competing risk of death can result in substantial overestimation of disease occurrence, which may give misleading results in estimating and comparing the occurrence of a disease of interest.

AIDS-Related Opportunistic Infections↗
PubMed2000

Engraftment and growth of patient-derived retinoblastoma tumour in severe combined immunodeficiency mice.

The development of an in vivo model of retinoblastoma could be important for studying its biological behaviour and developing novel therapeutic strategies. We examined the ability of patient-derived retinoblastoma cells to grow and disseminate in severe combined immunodeficiency CB-17-SCID mice after subcutaneous (s.c.) inoculation without conditioning treatment. 24/30 (80%) of patient-derived tumours engrafted and grew as s.c. nodules in SCID mice. Whilst most xenografted tumours appeared to be localised, by PCR assay a positive DNA band of human minisatellite region (YNZ.22) was determined in the bone marrow of 19/25 (76%), in the spleen of 14/25 (56%) and in the liver of 16/25 (64%) mice, respectively, indicating dissemination to distant organs. Cytogenetic analysis demonstrated i(6p) in 5/12 (42%) and trisomy 1 or 1q abnormalities in 8/12 (67%) of the xenografted tumour samples studied, respectively, suggesting that retinoblastoma tumour cells maintain their cytogenetic abnormalities following adoptive growth in SCID mice. In this report we demonstrate the ability to propagate human primary retinoblastoma cells in SCID mice after s.c. inoculation and suggest the possibility of using the SCID mouse model to study the intrinsic biological behaviour of human retinoblastoma and to develop novel therapeutic strategies in the treatment of this disease.

Animals↗
PubMed2000

Crystal structure of yeast Esa1 suggests a unified mechanism for catalysis and substrate binding by histone acetyltransferases.

Esa1 is the catalytic subunit of the NuA4 histone acetylase (HAT) complex that acetylates histone H4, and it is a member of the MYST family of HAT proteins that includes the MOZ oncoprotein and the HIV-1 Tat interacting protein Tip60. Here we report the X-ray crystal structure of the HAT domain of Esa1 bound to coenzyme A and investigate the protein's catalytic mechanism. Our data reveal that Esa1 contains a central core domain harboring a putative catalytic base, and flanking domains that are implicated in histone binding. Comparisons with the Gcn5/PCAF and Hat1 proteins suggest a unified mechanism of catalysis and histone binding by HAT proteins, whereby a structurally conserved core domain mediates catalysis, and sequence variability within a structurally related N- and C-terminal scaffold determines substrate specificity.

Acetyltransferases↗
PubMed2000

Hyperproduction of polyesters consisting of medium-chain-length hydroxyalkanoate monomers by strain Pseudomonas stutzeri 1317.

Pseudomonas stutzeri strain 1317 was found to grow on various fatty acids, alcohols, diols, as well as glucose and gluconate for the synthesis of polyhydroxyalkanoates (PHA) with various monomer units. The PHA monomer structures were dependent on the type of fatty acids and alcohols, as well as the diols in the culture media. Only even number monomers, such as 3-hydroxyhexanoate (HHx), 3-hydroxyoctanoate (HO) and 3-hydroxydecanoate (HD), were accumulated when even numbered fatty acids, alcohols, glucose and gluconate, as well as diol were used as carbon sources. Odd numbered fatty acids and odd numbered alcohols led to the formation of odd numbered monomers, such as 3-hydroxyvalerate (HV), 3-hydroxyheptanoate (HHp), 3-hydroxynonanoate (HN) and 3-hydroxyundecanoate (HU). The strain tolerated up to 1.5% of ethanol and made 8.3% of PHA when growth was conducted in 1.2% of ethanol. PHA formed up to 77% of cell dry weight when the strain was grown in tridecanoate. PHA synthesis was highly dependent on the nitrogen source. A depletion in nitrogen supply immediately resulted in PHA accumulation in cells grown in the glucose mineral medium.

Alcohols↗
PubMed2000

IgA nephropathy, the most common cause of glomerulonephritis, is linked to 6q22-23.

End-stage renal disease (ESRD) is a major public health problem, affecting 1 in 1,000 individuals and with an annual death rate of 20% despite dialysis treatment. IgA nephropathy (IgAN) is the most common form of glomerulonephritis, a principal cause of ESRD worldwide; it affects up to 1.3% of the population and its pathogenesis is unknown. Kidneys of people with IgAN show deposits of IgA-containing immune complexes with proliferation of the glomerular mesangium (Fig. 1). Typical clinical features include onset before age 40 with haematuria and proteinuria (blood and protein in the urine), and episodes of gross haematuria following mucosal infections are common; 30% of patients develop progressive renal failure. Although not generally considered a hereditary disease, striking ethnic variation in prevalence and familial clustering, along with subclinical renal abnormalities among relatives of IgAN cases, have suggested a heretofore undefined genetic component. By genome-wide analysis of linkage in 30 multiplex IgAN kindreds, we demonstrate linkage of IgAN to 6q22-23 under a dominant model of transmission with incomplete penetrance, with a lod score of 5.6 and 60% of kindreds linked. These findings for the first time indicate the existence of a locus with large effect on development of IgAN and identify the chromosomal location of this disease gene.

Chromosome Mapping↗
PubMed2000

Bovine FcgammaRIII with a single extracellular domain.

The full length of gene encoding Fc receptor types III for bovine immunoglobulin G (boFcgammaRIII, CD16) was obtained with PCR from the c DNA library of bovine alveolar macrophages. Through molecular cloning and sequencing it is shown that the coding gene has 507 bp and codes for 168 amino acids. There are signal peptide, transmembrane spanning domain and three potential N-linked glycosylation sites in the sequence. Compared with the boFcgammaRIII cDNA sequence cloned by Collins et al, it deletes 82 amino acids and has only one extracellular domain. It is suggested that this cDNA fragment is a special form of the gene structure of bovine FcgammaRIIIA (CD16-II).

Amino Acid Sequence↗
PubMed2000

Activity of acetyl-Ser-Asp-Lys-Pro (AcSDKP) on human hematopoietic progenitor cells in short-term and long-term bone marrow cultures.

The tetrapeptide acetyl-Ser-Asp-Lys-Pro (AcSDKP) is a potent inhibitor of hematopoietic stem cell proliferation. We examined the effects of AcSDKP on the production of granulocyte-macrophage colony-forming cells (CFU-GM) and high proliferative potential colony-forming cells (HPP-CFC) in human long-term bone marrow (LTBM) cultures and CFU-GM and erythroid burst-forming cells (BFU-e) in short-term liquid cultures. The addition of AcSDKP in short-term bone marrow cultures resulted in a maximum depression of the total number of progenitor cells as well as the number of progenitor cells entering cell cycle following culture with 10(-12) to 10(-14) M AcSDKP and 10(-14) M AcSDKP when exogenous cytokines (GM-CSF, IL-3, or SCF) were added. AcSDKP was added daily to LTBM cultures at various concentrations (10(-8) M to 10(-16) M) for up to 5 weeks. In these LTBM culture studies, AcSDKP inhibited the entry of nonadherent progenitor cells into S phase and decreased the number of nonadherent progenitor cells with peak activity at 10(-12) M. In contrast, AcSDKP had no effect on the number of adherent CFU-GM, HPP-CFC, or cellularity per culture or percent of adherent progenitor cells in S phase. These studies indicate that the concentration of the tetrapeptide is critical to the activity of AcSDKP on human hematopoietic progenitor cells. Furthermore, we report that the presence of cytokines or stromal cells also affects the response of progenitor cells to AcSDKP. These results will aid in determining kinetic properties of AcSDKP for the development of clinical protocols to protect normal human hematopoietic stem and progenitor cells following cycle-specific chemotherapy agents.

Bone Marrow Cells↗
PubMed2000

Clinical effectiveness of new stent design: randomized single-blind comparison of tail and double-pigtail stents.

BACKGROUND AND PURPOSE: Stent morbidity appears to be secondary to lower urinary tract irritation. In an effort to decrease stent morbidity, a "one size fits all" Tail stent (Microvasive [Boston Scientific] Natick, MA) was developed with a 7F proximal pigtail and 7F shaft which tapers to a lumenless straight 3F tail. PATIENTS AND METHODS: We randomized 60 patients in a single-blind fashion to a 7F tail stent or 7F double-pigtail Percuflex stent. Patients were evaluated at the time of stent removal and 2 weeks later with a standardized questionnaire assessing: irritative lower tract symptoms individually and on a total scale of 0 (no symptoms) to 30 (worst symptoms), obstructive lower tract symptoms (on a total scale of 0-20), and upper tract irritative symptoms (on a total scale of 0-10). RESULTS: Patient age, weight, and height were similar in the two groups. Complications, including fever, urinary tract infections, emergency room visits, and the need for antispasmodics and pain medication, also demonstrated no significant difference. At the time of stent removal, patients who received a tail stent had significantly less urinary frequency and a statistically significant (21%) decrease in overall irritative voiding symptoms (12.2 v 15.4; p = 0.048). Two weeks after stent removal, the total irritative voiding symptoms was markedly decreased in both groups (7.1 in the Tail v 5.3 in the double-pigtail group; p = 0.15). Obstructive bladder and flank symptoms were not significantly different in the two stent groups, either at the time of stent removal or at 2 weeks after removal. CONCLUSION: In this randomized, single-blind study, the 7F Tail stent produced significantly less irritative symptoms than did the standard 7F double-pigtail stent. Obstructive symptoms tended to be less with the new stent, while flank symptoms were similar.

Adult↗