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Biomedical subjects

J Wu

Publications and source records attributed to J Wu.

At least 271 records · Page 15Linked to original sources
PubMed2001

Novel HLA-B alleles identified in potential marrow donors: B*3917, B*1405 and B*3528.

Sequence-specific oligonucleotide probe hybridization and sequence-specific primer polymerase chain reaction (PCR) typing of volunteer bone marrow donors suggested the presence of variants of known HLA-B alleles in five individuals. PCR products encompassing HLA-B locus exons 1 through 3 were prepared and subcloned. Three African-American individuals had a novel HLA-B*39 allele (B*3917), and another African-American was found to have a novel HLA-B*14 allele (B*1405). In a third individual of Hispanic origin, a novel HLA-B*35 allele (B*3528) was identified. These findings further illustrate the substantial genetic variation present at the HLA-B locus within human populations.

Alleles↗
PubMed2001

Three new DP alleles identified in a study of 800 unrelated bone marrow donor-recipient pairs.

HLA-DP genotyping of 800 unrelated donor-recipient pairs in phase 5 of a retrospective analysis of unrelated bone marrow transplantation, sponsored by the National Marrow Donor Program (NMDP), has identified two new DPB1 alleles (DPB1*8701 and DBP1*8801) and one new DPA1 (DPA1*0108) allele. Sequencing confirmed that all three of these new alleles represent novel combinations of previously described sequence motifs, reinforcing the notion that "gene conversion-like" events play an important role in generating HLA allelic diversity. The identification of these new alleles brings the total number of DPA1 alleles to 20 and the total number of DPB1 alleles to 94.

Alleles↗
PubMed2001

Preoperative high-dose chemotherapy with peripheral blood stem cell support as a primary management of locally advanced breast cancer.

Locally advanced breast cancer (LABC) has a poor prognosis with a high risk of local recurrence and distant metastasis. Preoperative combined chemotherapy with or without granulocyte colony-stimulating factor (G-CSF) support does not improve the long-term survival rate. In our report, two patients with LABC received preoperative high-dose chemotherapy with peripheral blood stem cell support (HDC/PBSCs). Prior to high-dose chemotherapy with peripheral blood stem cell support, they both received induction chemotherapy of cyclophosphamide, epirubicin and 5-fluorouracil (FEC) for two cycles which resulted in a partial response. PBSC mobilization and collection were carried out following the second cycle of induction chemotherapy followed by G-CSF. High-dose cyclophosphamide (2500 mg/m2), carboplatin (600 mg/m2) and etoposide (600 mg/m2) were administered with PBSC support. A radical mastectomy was performed followed by adjuvant chemotherapy with FEC regimen for four cycles, followed by local irradiation, and endocrine therapy with tamoxifen. Both patients achieved a remarkable response in the primary lesion after HDC/PBSCs and tolerated the whole treatment well. Preoperative HDC/PBSCs as a new strategy in the treatment of LABC seems practical but it needs to be studied more deeply.

Adult↗
PubMed2001

Isolation and characterization of a novel type of neurotoxic peptide from the venom of the South African scorpion Parabuthus transvaalicus (Buthidae).

The venom of the South African scorpion Parabuthus transvaalicus was characterized using a combination of mass spectrometry and RP-HPLC separation and bioassays. The crude venom was initially separated into 10 fractions. A novel, moderately toxic but very high abundance peptide (birtoxin) of 58 amino-acid residues was isolated, identified and characterized. Each purification step was followed by bioassays and mass spectroscopy. First a C4 RP-HPLC column was used, then a C18 RP Microbore column purification resulted in > 95% purity in the case of birtoxin from a starting material of 230 microg of crude venom. About 12-14% of the D214 absorbance of the total venom as observed after the first chromatography step was composed of birtoxin. This peptide was lethal to mice at low microgram quantities and it induced serious symptoms including tremors, which lasted up to 24 h post injection, at submicrogram amounts. At least seven other fractions that showed different activities including one fraction with specificity against blowfly larvae were identified. Identification of potent components is an important step in designing and obtaining effective anti-venom. Antibodies raised against the critical toxic components have the potential to block the toxic effects and reduce the pain associated with the scorpion envenomation. The discovery of birtoxin, a bioactive long chain neurotoxin peptide with only three disulfide bridges, offers new insight into understanding the role of conserved disulfide bridges with respect to scorpion toxin structure and function.

Amino Acid Sequence↗
PubMed2001

Pancreatitis-associated protein-I mRNA expression in mouse pancreas is upregulated by lipopolysaccharide independent of cerulein-pancreatitis.

BACKGROUND AND AIMS: It is well known that endotoxemia, which is caused by a bacterial infection, can exacerbate acute pancreatitis, whereas pancreatitis-associated protein (PAP) has the ability to induce bacterial aggregation. Pancreatitis-associated protein is supposed to protect the tissue from infection during inflammation. In order to clarify the relationship between PAP mRNA expression and endotoxemia during acute pancreatitis, the kinetic patterns of PAP-I mRNA in mouse pancreas treated with either cerulein or lipopolysaccharide (LPS) or both were investigated in this study. METHODS AND RESULTS: The administration of LPS (5 mg/kg) intraperitoneally resulted in a dramatic upregulation of PAP-I mRNA expression, increasing 18.61-fold to a maximum at 12 h, then decreasing, but still sustaining at a high level and reaching baseline on day five. These changes were accompanied by the upregulation of tumor necrosis factor (TNF)-alpha, interleukin-1beta (IL-1beta), interleukin 6 (IL-6) and interferon gamma (IFNgamma) mRNA expressions in the pancreas, but not by marked alterations of serum amylase, lactic dehydrogenase (LDH) and histology. Cerulein also increased PAP-I mRNA expression. However, the combination of cerulein and LPS was not able to enhance PAP-I mRNA expression further, although more prominent pancreatitis based on significant changes of serum amylase, LDH and histology were observed. CONCLUSION: These results suggest that PAP-I mRNA might be modulated by endotoxemia, independent of cerulein-pancreatitis. There were no strong correlations between PAP-I mRNA expression and the severity of pancreatitis.

Acute Disease↗
PubMed2001

Functional gamma-secretase inhibitors reduce beta-amyloid peptide levels in brain.

Converging lines of evidence implicate the beta-amyloid peptide (Ass) as causative in Alzheimer's disease. We describe a novel class of compounds that reduce A beta production by functionally inhibiting gamma-secretase, the activity responsible for the carboxy-terminal cleavage required for A beta production. These molecules are active in both 293 HEK cells and neuronal cultures, and exert their effect upon A beta production without affecting protein secretion, most notably in the secreted forms of the amyloid precursor protein (APP). Oral administration of one of these compounds, N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester, to mice transgenic for human APP(V717F) reduces brain levels of Ass in a dose-dependent manner within 3 h. These studies represent the first demonstration of a reduction of brain A beta in vivo. Development of such novel functional gamma-secretase inhibitors will enable a clinical examination of the A beta hypothesis that Ass peptide drives the neuropathology observed in Alzheimer's disease.

Administration, Oral↗
PubMed2001

How accurate are physicians' clinical predictions of survival and the available prognostic tools in estimating survival times in terminally ill cancer patients? A systematic review.

The purpose of this review was to examine the accuracy of physicians' clinical predictions of survival and the available prognostic tools in estimating survival times in terminally ill cancer patients. A MEDLINE search for English language articles published between 1966 and March 2000 was performed using the following keywords: forecasting/clinical prediction, prognosis/prognostic factors, survival and neoplasm metastasis. Searches in CancerLit, EMBASE, PubMed, the Cochrane Library and reference sections of articles were performed. Studies were included if they concerned adult patients with various cancer histological diagnoses and employed clinical prediction and the readily available clinical parameters. Biochemical and molecular markers were excluded. Grading of the evidence and recommendations was performed. Twelve articles on clinical prediction and 19 on prognostic factors met the inclusion criteria. Clinical prediction tends to be incorrect in the optimistic direction but improves with repeated measurements. Performance status has been found to be most strongly correlated with the duration of survival, followed by the 'terminal syndrome', which includes anorexia, weight loss and dysphagia. Cognitive failure and confusion have also been associated with a shorter life span. Performance status combined with clinical symptoms and the clinician's estimate helps to guide an accurate prediction, as reviewed in an Italian series. There is fair evidence to support using performance status, and clinical and biochemical parameters, in addition to clinicians' judgement to aid survival prediction. However, there is weak evidence to support that clinicians' estimates alone could be specifically employed for survival prediction.

Cognition Disorders↗
PubMed2001

A tripartite anoikis-like mechanism causes early isolated islet apoptosis.

BACKGROUND: This study examines the mechanisms of early isolated islet apoptosis (II-APO) and loss of functional islet mass. METHODS: Rhesus islets were isolated for transplantation, and an aliquot was used for in vitro molecular studies of II-APO. These studies used Western blotting to examine caspase activation and perinuclear envelope protein cleavage that are associated with II-APO and used immunofluorescence analysis of Annexin V and mitochondrial permeability index to examine spontaneous and tripartite anoikis-like (TRAIL) mechanism--induced II-APO. RESULTS: Caspase 6 was prominently activated in association with spontaneous II-APO, which occurred after overnight culture. In contrast, caspase 7, 8, and 9 were not activated. Cleavage of focal adhesion kinase and Lamin, substrates of caspase 6, was also evident in spontaneous II-APO. II-APO was exaggerated by the addition of the TRAIL mechanism. The TRAIL mechanism--induced II-APO was blocked by the caspase 6 inhibitor, VEID, and by the soluble fusion proteins, DR4 or DR5, which act as decoy receptors. In vivo studies in diabetic severe combined immunodeficiency disease mice showed that rhesus islets were cytoprotected by either ex vivo gene transfer of Bcl-2 or treatment of the isolated islet with VEID. CONCLUSIONS: These studies suggest 3 major mechanisms involved in II-APO: caspase 6 activation, a TRAIL-induced apoptosis pathway, and the mitochondrial-associated apoptosis pathway. Inhibition of these II-APO pathways may improve isolated islet survival and reduce functional islet mass loss, which compromises the stable reversal of diabetes.

Animals↗
PubMed2001

Can tumor size be a guide for limited surgical intervention in patients with peripheral non-small cell lung cancer? Assessment from the point of view of nodal micrometastasis.

OBJECTIVE: We sought to determine the critical diameter of a peripheral non-small cell lung cancer tumor less than which no evidence of nodal micrometastasis is present. METHODS: Samples of 3081 lymph nodes from 181 patients with stage I peripheral lung cancer (155 with adenocarcinoma and 26 with squamous cell carcinoma) who had undergone complete resection with systematic lymphadenectomy were used in the study. In the samples immunohistochemical staining for cytokeratin was performed. The expression of vascular endothelial growth factor (VEGF) at primary sites was also immunohistochemically assessed. RESULTS: Nodal micrometastasis was detected in 44 patients. The mean tumor sizes were 2.2 +/- 1.3 cm (range, 1.0-7.0 cm) in nodal micrometastasis-positive adenocarcinoma, 2.1 +/- 0.9 cm (range, 0.5-6.0 cm) in nodal micrometastasis-negative adenocarcinoma, 4.8 +/- 2.3 cm (range, 2.2-10.0 cm) in nodal micrometastasis-positive squamous cell carcinoma, and 3.2 +/- 2.1 cm (range, 0-9.0 cm) in nodal micrometastasis-negative squamous cell carcinoma. The tumor size in the nodal micrometastasis-positive group tended to be greater than that in the nodal micrometastasis-negative group in squamous cell carcinomas, but there was no significant difference in adenocarcinomas. Nodal micrometastasis was not found in patients with squamous cell carcinoma of 2.0 cm or less in diameter. However, nodal micrometastasis was found in 20% (19/95) of the patients with adenocarcinoma of 1.1 to 2.0 cm in diameter and even in 4 of 11 patients with adenocarcinoma of 1.0 cm or less. Among the patients with nodal micrometastasis, survival of patients with vascular endothelial growth factor overexpression was worse than that of patients without it. The survival of patients with nodal micrometastasis without vascular endothelial growth factor overexpression was comparable with that of patients without nodal micrometastasis. CONCLUSION: A limited surgical intervention without lymphadenectomy is validated for squamous cell carcinoma of 2.0 cm or less without pleural involvement. In adenocarcinoma the tumor size itself is not a reliable guide for nodal micrometastasis status. In patients with nodal micrometastasis with vascular endothelial growth factor overexpression, the risk of systemic disease should be considered.

Adenocarcinoma↗
PubMed2001

Effects of some water-quality and operating parameters on the decolorization of reactive dye solutions by ozone.

The ozonation of reactive dye solutions has been investigated. Results of studies on ozone mass transfer indicated that the volumetric mass transfer coefficient of ozone increased with the following water-quality and operating parameters: pH, initial dye concentration, applied ozone dose, and temperature. A model was developed to predict the volumetric mass transfer coefficient of ozone from the above parameters. The results of kinetic studies showed that ozonation of the aqueous reactive dye was a pseudo-first-order reaction with respect to the dye. The apparent rate constant increased with the pH, applied ozone dose and temperature, however, it declined logarithmically with the initial dye concentration. Meanwhile, Ozonation enhanced the biodegradability and reduced the COD of the reactive dye wastewater effectively.

Biodegradation, Environmental↗
PubMed2001

Osmotic stress-mediated activation of RET kinases involves intracellular disulfide-bonded dimer formation.

We showed that osmotic stress induces activation of c-RET and second-set activation of constitutively activated RET-MEN2B. A few percentage of RET proteins normally formed disulfide-bonded dimers in the cell, and osmotic stress promoted formation of these dimers. The disulfide-bonded dimers displayed higher levels of autophosphorylation and catalytic activity per molecule than did monomers. Osmotic stress also promoted activation and disulfide-bonded dimerization of the extracellular domain-depleted mutant RET (RET-PTC-1), suggesting that the target amino acid(s) for dimerization is located intracellularly rather than in the cysteine-rich region of the extracellular domain. In the mutant c-RET and RET-PTC-1 in which Cys987 of c-RET or Cys376 of RET-PTC-1 was replaced with Ala, the levels of intrinsic kinase activity were greatly reduced and barely increased in response to osmotic stress. Correspondingly, the Cys376-defective RET-PTC-1 did not form any demonstrable levels of dimers even after exposure to osmotic stress. In contrast, another RET-PTC-1 mutant that had a replacement of Cys365 with Ala mostly behaved like parental RET-PTC-1. These results suggest that Cys987 of c-RET or Cys376 of RET-PTC-1 plays a crucial role in maintenance and promotion of dimerization and activation of the RET kinases.

3T3 Cells↗
PubMed2001

Pharmacology of caspase inhibitors in rabbit cardiomyocytes subjected to metabolic inhibition and recovery.

Protection of ischemic myocardium is an important unmet need in reperfusion therapy of acute myocardial infarction. Myocardial ischemia and reperfusion induce necrosis and apoptosis in cardiomyocytes. Caspase processing and activation are critical steps in most receptor and nonreceptor pathways of apoptosis. Caspase inhibitors have been shown to reduce ischemia reperfusion injury in cardiac muscle. Information about dose response and time of administration are needed to optimize the design of preclinical studies. We used isolated adult rabbit cardiomyocytes subjected to metabolic inhibition (MI) and recovery to examine the role of caspases and caspase inhibitors, the dose response, and the timing of administration. In vitro inhibitory concentrations (Ki) were determined for purified caspases. Cardiomyocytes subjected to MI were treated with peptidomimetic fluoromethyl ketone inhibitors of caspases before or during MI, or at recovery. Caspase inhibitors were most effective when added before MI and included throughout recovery, but were partially protective if added after MI. The optimal concentration of the inhibitors tested was approximately 10 microM. Protection was sustained when cells were allowed to recover for 4 or 24 h. These results suggest that caspase activation is an important component of myocyte injury mediated by MI and recovery. Low doses of caspase inhibitors were identified that reduce injury in this model system, and further investigations using in vivo models are warranted.

Animals↗
PubMed2001

Antisense expression of a rice sucrose transporter OsSUT1 in rice (Oryza sativa L.).

We analyzed the function of a rice sucrose transporter, OsSUT1, by using antisense rice. There was no difference between antisense and wild-type plants in carbohydrate content and photosynthetic ability of the flag leaves in the vegetative growth stage, suggesting that OsSUT1 may not play an important role in carbon metabolism, at least in these materials.

Base Sequence↗
PubMed2001

In vitro growth, maturation, fertilization, and embryonic development of oocytes from porcine preantral follicles.

This study was conducted to identify an in vitro culture system that would support intact porcine follicle growth from preantral follicle to antral stages, oocyte maturation, fertilization, and embryonic development; and to evaluate factors that influence porcine preantral follicle growth in vitro. Preantral follicles isolated from prepubertal porcine ovaries were cultured for 4 days in the presence of different concentrations of porcine serum and FSH, and with different numbers of follicles per well. A series of experiments showed that porcine antral follicles can be grown at a high frequency in vitro from healthy preantral follicles with intact theca when cultured in North Carolina State University 23 medium supplemented with 1.5 ng/ml FSH, 7.5% serum, and when cultured with three follicles per well. After 4 days of culture, 68% healthy cumulus-enclosed oocytes from these follicles were obtained, and 51% of the oocytes completed meiotic maturation to the metaphase II stage. Fifty-three percent of the mature oocytes underwent fertilization, 43% of the fertilized oocytes cleaved, and 13% developed to the blastocyst stage. The results show 1) that porcine preantral follicles can grow efficiently to the antral stage using these culture conditions, and 2) that oocytes from in vitro-matured porcine preantral follicles can acquire meiotic competence and undergo fertilization and embryonic development.

Animals↗
PubMed2001

Development of in vitro-matured oocytes from porcine preantral follicles following intracytoplasmic sperm injection.

The objective of this study was to assess fertilization and embryonic development following intracytoplasmic sperm injection (ICSI) of oocytes from porcine preantral follicles matured in vitro. Also, another aim was to describe actin filament distribution during fertilization and embryonic development of those oocytes after ICSI as one of the factors assessed. Preantral follicles isolated from prepubertal porcine ovaries were cultured in a system that supports follicular development. After in vitro maturation, the oocytes were fertilized by ICSI or conventional fertilization in vitro (IVF). Actin filaments of the fertilized oocytes and embryos produced by ICSI or IVF were stained by rhodamine-phalloidin and visualized by fluorescence microscopy. ICSI resulted in 64% fertilization of porcine preantral follicle oocytes matured in vitro. Of those, 51% of the fertilized oocytes cleaved and 21% developed to the blastocyst stage. No significant differences in percentages of oocyte fertilization, cleavage, and blastocyst formation were observed between ICSI and IVF (53%, 45% and 16%, respectively). Actin filament distribution during fertilization and embryonic development of ICSI- or IVF-fertilized oocytes from porcine preantral follicles was similar to that of oocytes derived from antral follicles and fertilized by standard IVF. These results indicate that oocytes from porcine preantral follicles matured in vitro following ICSI can undergo fertilization and subsequent embryonic development.

Actins↗
PubMed2001

Beneficial effects of growth hormone on bacterial translocation during the course of acute necrotizing pancreatitis in rats.

Because bacterial translocation from the gut is one of the important sources of bacterial infection in acute necrotizing pancreatitis (ANP) and growth hormone (GH) has the ability to promote the intestinal epithelial proliferation, we investigated the effects of GH on bacterial translocation in a rat ANP model. ANP was induced in rats by injection of 5% sodium taurocholate into the biliopancreatic duct. The rats with ANP were treated with either human recombinant GH or placebo. Laparotomized animals without induction of ANP (sham operation [SO]) served as controls. At 24 hours after operation, blood was drawn for bacterial culture and determination of amylase, lipase, and endotoxin. Peritoneal fluid and specimens of mesenteric lymph nodes (MLN), liver, pancreas, and spleen were taken for bacterial culture by standard techniques. Intestinal mucosal permeability was assessed by measuring the movement of 125I-labeled albumin from blood to intestinal lumen. Insulin-like growth factor-1 (IGF-1) mRNA was detected in the liver and ileum by reverse transcriptase-polymerase chain reaction (RT-PCR). Morphologic changes of pancreas and ileum were also analyzed. Administration of GH significantly decreased the serum amylase, lipase activities, plasma endotoxin level, and incidence of bacterial translocation. Moreover, the survival rate of ANP rats was improved. The severity of inflammation in pancreas and ileum was alleviated by GH treatment. Ileal mucosal thickness, villus height, and crypt depth in GH treatment rats were obviously increased compared with those of ANP rats. The intestinal permeability was markedly improved in the GH group versus the ANP group. GH treatment resulted in up-regulation of IGF-1 mRNA expression in ileum, but not in liver. These results suggested that exogenous GH had beneficial effects in maintaining the integrity of intestinal mucosal barrier and reducing the incidence of bacterial translocation in rats with ANP. One of the mechanisms might be the up-regulation of IGF-1 mRNA in intestine by GH treatment.

Amylases↗