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B Wang

Publications and source records attributed to B Wang.

At least 145 records · Page 8Linked to original sources
PubMed2001

Population pharmacokinetic-pharmacodynamic modeling of filgrastim (r-metHuG-CSF) in healthy volunteers.

The pharmacokinetic-pharmacodynamic (PK-PD) relationship of the granulopoietic effects of Filgrastim in healthy volunteers was characterized via a population approach. Healthy male volunteers were enrolled into a four-way crossover clinical trial. Subjects received four single doses of Filgrastim (375 and 750 micrograms i.v. and s.c.) with an intervening washout period of 7 days. Serum concentrations of Filgrastim were determined using an enzyme-linked immunosorbent assay. Absolute neutrophil count (ANC) was determined. Data analysis was performed using mixed-effects modeling as implemented in the NONMEM software package. The final PKPD model incorporates a two-compartment PK model with bisegmental absorption from the s.c. site, first-order and saturable elimination pathways, and an indirect PD model. A sigmoidal Emax model for the stimulation of ANC input rate (kin) was superior to the conventional Emax model (mean +/- SE: Emax = 12.7 +/- 1.7; EC50 = 4.72 +/- 0.72 ng/ml; Hill = 1.34 +/- 0.19). In addition, a time-variant scaling factor for ANC observations was introduced to account for the early transient depression of ANC after Filgrastim administration. The absolute bioavailability of subcutaneously administered Filgrastim was estimated to be 0.619 +/- 0.058 and 0.717 +/- 0.028 for 375 micrograms and 750 micrograms s.c. doses, respectively. The time profiles of concentration and ANC, as well as the concentration approximately ANC relationship of Filgrastim in healthy volunteers were well described by the developed population PK-PD model.

Adolescent↗
PubMed2001

Glutamatergic components of the retrosplenial granular cortex in the rat.

The ultrastructural characteristics, distribution and synaptic relationships of identified, glutamate-enriched thalamocortical axon terminals and cell bodies in the retrosplenial granular cortex of adult rats is described and compared with GABA-containing terminals and cell bodies, using postembedding immunogold immunohistochemistry and transmission electron microscopy in animals with injections of cholera toxin- horseradish peroxidase (CT-HRP) into the anterior thalamic nuclei. Anterogradely labelled terminals, identified by semi-crystalline deposits of HRP reaction product, were approximately 1 microm in diameter, contained round, clear synaptic vesicles, and established asymmetric (Gray type I) synaptic contacts with dendritic spines and small dendrites, some containing HRP reaction product, identifying them as dendrites of corticothalamic projection neurons. The highest densities of immunogold particles following glutamate immunostaining were found over such axon terminals and over similar axon terminals devoid of HRP reaction product. In serial sections immunoreacted for GABA, these axon terminals were unlabelled, whereas other axon terminals, establishing symmetric (Gray type II) synapses were heavily labelled. Cell bodies of putative pyramidal neurons, containing retrograde HRP label, were numerous in layers V-VI; some were also present in layers I-III. Most were overlain by high densities of gold particles in glutamate but not in GABA immunoreacted sections. These findings provide evidence that the terminals of projection neurons make synaptic contact with dendrites and dendritic spines in the ipsilateral retrosplenial granular cortex and that their targets include the dendrites of presumptive glutamatergic corticothalamic projection neurons.

Animals↗
PubMed2001

Activation of EphA receptor tyrosine kinase inhibits the Ras/MAPK pathway.

Interactions between Eph receptor tyrosine kinases (RTKs) and membrane-anchored ephrin ligands critically regulate axon pathfinding and development of the cardiovascular system, as well as migration of neural cells. Similar to other RTKs, ligand-activated Eph kinases recruit multiple signalling and adaptor proteins, several of which are involved in growth regulation. However, in contrast to other RTKs, activation of Eph receptors fails to promote cell proliferation or to transform rodent fibroblasts, indicating that Eph kinases may initiate signalling pathways that are distinct from those transmitted by other RTKs. Here we show that stimulation of endogenous EphA kinases with ephrin-A1 potently inhibits the Ras/MAPK cascade in a range of cell types, and attenuates activation of mitogen-activated protein kinase (MAPK) by receptors for platelet-derived growth factor (PDGF), epidermal growth factor (EGF) and vascular endothelial growth factor (VEGF). In prostatic epithelial cells and endothelial cells, but not fibroblasts, treatment with ephrin-A1 inhibits cell proliferation. Our results identify EphA kinases as negative regulators of the Ras/MAPK pathway that exert anti-mitogenic functions in a cell-type-specific manner.

Animals↗
PubMed2001

Leptin concentrations in relation to overall adiposity, fat distribution, and blood pressure in a rural Chinese population.

OBJECTIVE: To examine the associations between leptin levels and body mass index (BMI), fat distribution (reflected by waist to hip ratio and skinfold measurements), and blood pressure in a rural Chinese population. DESIGN AND SUBJECTS: A cross-sectional study of 294 participants who provided blood samples. MEASUREMENTS: Plasma concentrations of leptin, BMI, waist to hip ratio, skinfold thickness, and blood pressure. RESULTS: The average leptin concentration was 5.2 microg/l (3.1 for men and 7.3 for women). In univariate analyses, leptin levels were significantly correlated with BMI (r=0.47), abdominal skinfold thickness (r=0.53), triceps skinfold thickness (r=0.56), waist circumference (r=0.41), hip circumference (r=0.51), waist to hip ratio (r=0.17), and diastolic blood pressure (r=0.13). In multivariate analyses controlling for age, sex, education, current smoking, and alcohol use, independent associations between leptin levels and BMI, waist to hip ratio, waist circumference, and abdominal skinfold thickness remained. However, the significant association between leptin and blood pressure disappeared after adjusting for BMI, whereas the association between BMI and blood pressure persisted after adjusting for leptin level. CONCLUSIONS: We observed a strong positive relationship between overall adiposity and leptin levels in both men and women in a rural Chinese population. In addition, leptin concentrations were significantly associated with central obesity measured by waist to hip ratio and abdominal skinfold, independent of overall obesity. The observed positive association between leptin and blood pressure was largely explained by BMI. International Journal of Obesity (2001) 25, 121-125

Adipose Tissue↗
PubMed2001

Impaired ultraviolet-B-induced cytokine induction in xeroderma pigmentosum fibroblasts.

Xeroderma pigmentosum is a rare, autosomal recessive disease in which patients develop excessive solar damage at an early age and have a 1000-fold increased risk of developing cutaneous neoplasms. Xeroderma pigmentosum can be classified into seven complementation groups (A-G) with defects in different DNA nucleotide excision repair genes. Xeroderma pigmentosum patients also have impaired immune function including reduced natural killer cell activity and impaired induction of interferon-gamma. We hypothesized that altered cytokine induction may contribute to the immune defect in xeroderma pigmentosum patients. We examined cytokine mRNA expression after ultraviolet B irradiation using reverse transcriptase polymerase chain reaction in fibroblasts derived from five xeroderma pigmentosum patients in complementation groups A, C, and D and in complemented XP-A and XP-D cells. Cytokines interleukin-1beta and interleukin-6 displayed impaired ultraviolet B induction whereas interleukin-8 had normal induction in the xeroderma pigmentosum fibroblasts. Stable complementation of XP-A and XP-D cell lines increased ultraviolet-B-induced interleukin-1beta and interleukin-6 expression. These results demonstrate a deficient response of xeroderma pigmentosum fibroblasts to ultraviolet B in terms of cytokine interleukin-1beta and interleukin-6 induction but normal interleukin-8 induction and exhibit a role for DNA repair in cytokine induction.

Cell Line↗
PubMed2001

Rethinking the role of tumour necrosis factor-alpha in ultraviolet (UV) B-induced immunosuppression: altered immune response in UV-irradiated TNFR1R2 gene-targeted mutant mice.

BACKGROUND: Ultraviolet (UV) B-induced immunosuppression, implicated in the pathogenesis of skin cancers, is postulated to be mediated in part by cis-urocanic acid (cis-UCA) via tumour necrosis factor (TNF)-alpha. TNF-alpha produces morphological changes in Langerhans cells indistinguishable from those induced by UVB exposure and antibodies against TNF-alpha have been demonstrated to inhibit UVB-induced immunosuppression in vivo. OBJECTIVES: To clarify further the role of TNF-alpha in UVB-induced immunosuppression and in cis-UCA immunosuppression. METHODS: We performed a contact hypersensitivity (CHS) assay on gene-targeted mutant mice (TNFR1R2-/-) lacking genes for both receptors (p55 and p75) for TNF-alpha. Mice were either irradiated with UVB or injected intradermally with cis-UCA, sensitized with 2,4-dinitrofluorobenzene, challenged on the ears and the response was measured. RESULTS: The TNFR1R2-/- mice showed hyporesponsiveness in the CHS response compared with wild-type (P < 0.001), confirming the proinflammatory role of TNF-alpha. However, significant suppression of CHS was seen after irradiation and after cis-UCA injection in both locally (sensitization on irradiated site; P < 0.05) and systemically (sensitization on non-irradiated site; P < 0.05) sensitized wild-type and gene-targeted mice. CONCLUSIONS: These results demonstrate that TNF-alpha signalling is only partially involved in UVB-induced immunosuppression and does not play a major part in the cis-UCA immunosuppression mechanism.

Animals↗
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

Apoptosis and JNK activation are differentially regulated by Fas expression level in renal tubular epithelial cells.

BACKGROUND: In chronic renal disease, renal tubular epithelial cell (RTC) Fas expression is up-regulated, leading to apoptotic RTC deletion and tubular atrophy. In vitro, cytokine- or hypoxia-induced up-regulation of Fas expression is associated with RTC apoptosis. In contrast, constitutively expressed, low level RTC Fas does not mediate apoptosis, suggesting that Fas may be coupled to expression level-dependent RTC signaling pathways. Fas is known to signal through JNK in many systems, but the requirement of JNK activation for apoptosis remains controversial. METHODS: To determine if RTC Fas regulates JNK activity and apoptosis, human RTC were transfected with graded concentrations of a eukaryotic expression vector for murine Fas. Apoptosis was measured by annexin V, TUNEL and PARP cleavage assays. JNK activity was determined by immune complex kinase assay and/or immunoblots with phospho-specific JNK antibodies, in the presence or absence of co-expressed dominant negative JNK constructs. RESULTS: Fas antibody stimulation of RTC with high Fas expression levels (to model RTC phenotype in renal disease) caused a tenfold increase in apoptosis, while RTC with low level Fas expression (to model normal RTC phenotype) were apoptosis-resistant. Fas ligation activated JNK in RTC expressing low levels of Fas, but not in apoptosis-sensitive RTC with increased Fas expression. Dominant negative JNK co-expression failed to inhibit apoptosis in RTC expressing high levels of Fas, suggesting that JNK is neither necessary, nor sufficient, for Fas-dependent apoptosis. CONCLUSIONS: At high levels of expression, RTC Fas promotes apoptosis in a JNK-independent manner. At low basal expression, Fas induces JNK activation, but not apoptosis, consistent with novel roles for RTC Fas as a mediator of cell stress or chronic inflammation.

Animals↗
PubMed2001

Lipopolysaccharide results in a marked decrease in hepatocyte nuclear factor 4 alpha in rat liver.

The acute-phase response can result in decreased liver-specific functions and death as a result of liver failure. We show here that lipopolysaccharide (LPS), an endotoxin that induces the acute-phase response, results in a marked decrease in the major isoforms of the transcription factor, hepatocyte nuclear factor 4 alpha (HNF-4 alpha), in livers of rats. HNF-4 alpha is a nuclear receptor that is critical for the expression of several liver-specific genes. This decrease in HNF-4 alpha is primarily the result of a posttranscriptional mechanism, because mRNA levels are normal, and there are no major changes in the splicing patterns. This decrease was of functional significance, because expression of a gene that is highly dependent on HNF-4 alpha, HNF-1 alpha, was reduced. Interleukin-1 beta (IL-1 beta) is a cytokine whose levels are increased in vivo in response to LPS. IL-1 beta resulted in a decrease in HNF-4 alpha levels in HepG2 cells. This IL-1 beta-induced decrease was likely caused by degradation via the proteasome, because it was prevented by the addition of the proteasome inhibitor, MG132. We conclude that the decrease in HNF-4 alpha that occurs in vivo after the administration of LPS may be the result of IL-1 beta-induced degradation, and likely contributes to the liver insufficiency that occurs. IL-1 beta antagonists or proteasome inhibitors might increase HNF-4 alpha protein levels in the acute-phase response, which could result in increased liver function and survival.

Animals↗
PubMed2001

Correction of scapular winging by supraclavicular neurolysis of the long thoracic nerve.

Injury to the long thoracic nerve results in winging of the scapula. When there is no known direct site of injury to this nerve, the traditional treatment consists of bracing the shoulder and, if recovery of function does not occur, then carrying out a muscle transfer to reconstitute the forces required to bring the scapula into appropriate position with respect to the thorax. The present report describes four patients in whom a site of compression of the long thoracic nerve within the scalene muscles proved to be the site of compression. A supraclavicular neurolysis of the long thoracic nerve resulted in correction of the winged scapula in all four of these patients.

Adult↗
PubMed2001

Indications for immediate tissue transfer for soft tissue reconstruction in visceral pelvic surgery.

BACKGROUND: Perineal wound complications may occur after visceral pelvic surgery. We reviewed our experience to determine indications for immediate tissue transfer (TT) to prevent complications. METHODS: Hospital records and computerized data were reviewed on 175 perineal repairs in 156 patients treated at The University of Texas M.D. Anderson Cancer Center for tumors involving the alimentary tract (135 of 175), genitourinary tract (15 of 175), perineum (19 of 175), or sacrum (6 of 175). Patients had either resection of only the colorectum and anus (APR) (46 of 175) or multivisceral resection (MVR) (129 of 175), and the perineal wound was closed by using TT (108 of 175) or primary closure (PC) (67 of 175) on the basis of the surgeon's judgment. Complications were compared between PC and TT groups. RESULTS: Complications occurred in 57% (100 of 175). There was no significant difference overall in PC and TT procedures or in the APR subgroup. There were significantly fewer complications for TT patients in the MVR subgroup (P =.0001). There were significantly fewer complications for TT patients with prior irradiation in both APR (P =.01) and MVR (P =.007) subgroups. CONCLUSIONS: Immediate TT for perineal wound closure is associated with fewer healing complications than PC in a subset of patients with multivisceral resection or prior radiotherapy. Surgical planning in these cases should consider immediate soft tissue reconstruction.

Adult↗
PubMed2001

Saikosaponin v-1 from roots of Bupleurum chinense DC.

Three triterpenoidal saponins, saikosaponin v-1(1), 6"-O-acetyl-saikosaponin b2 (2) and 6"-O-acetyl-saikosaponin d(3) were isolated from the roots of the title plant and the structures were identified on the basis of spectral analysis. Saikosaponin v-1 is a new compound, which was identified as 3beta,16alpha,23,28-tetrahydroxy-olean-11,13(18)-dien-30-oic acid-3-O-beta-D-glucopyranosyl-(1-->3)-beta-D-fucopyranosyl-30-O-xylitol ester.

Adjuvants, Immunologic↗
PubMed2001

Regulation of interleukin-8 expression by nitric oxide in human pancreatic adenocarcinoma.

The regulation of interleukin-8 (IL-8) expression by nitric oxide (NO) was determined in human pancreatic cancer cell lines. CaPan-2 and FG human pancreatic adenocarcinoma cells were incubated for 24 h in medium alone or medium containing a cytokine mixture in the presence or absence of an NO synthase (NOS) inhibitor, N(G)-monomethyl-L-arginine (NMA). The NOS activity and level of IL-8 expression were determined. IL-8 expression was induced in the two cell lines. A low level of NOS activity was detectable only in CaPan-2 cells. Moreover, the presence of NMA did not reverse the induction of IL-8. The FG cells were then engineered to produce a physiologic level of NO and incubated in medium alone or medium containing 1 mM NMA. No significant IL-8 expression was induced in those producing a low level of NO, whereas IL-8 expression was induced in those producing a high level of NO. Inhibition of NO production by NMA reversed this effect. Incubation of FG cells with an NO donor, S-nitroso-D,L.-acetyl-penicillamine (SNAP), led to a concentration-dependent and time-dependent induction of IL-8 expression. This NO-mediated upregulation of IL-8 expression correlated with an increase in IL-8 gene transcription and mRNA stability. Our results indicate that NO is involved in the regulation of IL-8 expression in and contributes to the progression of human pancreatic cancer.

Adenocarcinoma↗
PubMed2001

Concentration and distribution of sialic acid in human milk and infant formulas.

BACKGROUND: In animal studies, sialic acid supplementation is associated with increases of gangliosides in the brain and improved learning ability. Only limited data are available on the sialic acid content of human milk and infant formulas. OBJECTIVE: We compared the concentrations of oligosaccharide-bound, protein-bound, and free sialic acid in milk from mothers of full-term and preterm infants and in a range of infant formulas. DESIGN: The milk from 20 and 14 mothers of full-term and preterm infants (mean gestational age: 31 +/- 3 wk), respectively, was collected at 4 stages of lactation (colostrum, transition, 1 mo, and 3 mo) and compared with 21 different infant formulas. RESULTS: Total sialic acid concentrations were highest in colostrum (x +/- SEM: 5.04 +/- 0.21 mmol/L in full term) and decreased by nearly 80% over the next 3 mo. Human milk from mothers of preterm infants contained 13-23% more sialic acid than did milk from mothers of full-term infants at 3 of the 4 lactation stages (P < 0.02). The sialic acid content of most formulas was <25% of that found in mature human milk (P < 0.01). Most of the sialic acid in the formulas ( approximately 70%) was bound to glycoproteins, whereas in human milk most sialic acid was bound to free oligosaccharides. CONCLUSIONS: Human milk, including milk from mothers of preterm infants, is a rich source of oligosaccharide-bound sialic acid, which contrasts with the relatively small amounts found in infant formulas. The nutritional significance of sialic acid is presently unknown, but it is plausible that it is a conditional nutrient that contributes to sialic acid accretion in the brain.

Adult↗
PubMed2001

Bacterial artificial chromosome-based physical map of the rice genome constructed by restriction fingerprint analysis.

Genome-wide physical mapping with bacteria-based large-insert clones (e.g., BACs, PACs, and PBCs) promises to revolutionize genomics of large, complex genomes. To accelerate rice and other grass species genome research, we developed a genome-wide BAC-based map of the rice genome. The map consists of 298 BAC contigs and covers 419 Mb of the 430-Mb rice genome. Subsequent analysis indicated that the contigs constituting the map are accurate and reliable. Particularly important to proficiency were (1) a high-resolution, high-throughput DNA sequencing gel-based electrophoretic method for BAC fingerprinting, (2) the use of several complementary large-insert BAC libraries, and (3) computer-aided contig assembly. It has been demonstrated that the fingerprinting method is not significantly influenced by repeated sequences, genome size, and genome complexity. Use of several complementary libraries developed with different restriction enzymes minimized the "gaps" in the physical map. In contrast to previous estimates, a clonal coverage of 6.0-8.0 genome equivalents seems to be sufficient for development of a genome-wide physical map of approximately 95% genome coverage. This study indicates that genome-wide BAC-based physical maps can be developed quickly and economically for a variety of plant and animal species by restriction fingerprint analysis via DNA sequencing gel-based electrophoresis.

Chromosomes, Artificial, Bacterial↗
PubMed2001

Effects of salt treatment and osmotic stress on V-ATPase and V-PPase in leaves of the halophyte Suaeda salsa.

The Chenopodiaceae Suaeda salsa L. was grown under different salt concentrations and under osmotic stress. The fresh weight was markedly stimulated by 0.1 M NaCl, 0.4 M NaCl and 0.1 M KCl and reduced by osmotic stress (PEG iso-osmotic to 0.1 M NaCl). Treatment with 0.4 M KCl severely damaged the plants. Membrane vesicle fractions containing tonoplast vesicles were isolated by sucrose gradient from leaves of the S. salsa plants and modulations of V-ATPase and V-PPase depending on the growth conditions were determined. Western blot analysis revealed that V-ATPase of S. salsa consists of at least nine subunits (apparent molecular masses 66, 55, 52, 48, 36, 35, 29, 18, and 16 kDa). This polypeptide pattern did not depend on culture conditions. V-PPase is composed of a single polypeptide (69 kDa). An additional polypeptide (54 kDa) was detected in the fractions of NaCl-, KCl- and PEG-treated plants. It turned out that the main strategy of salt-tolerance of S. salsa seems to be an up-regulation of V-ATPase activity, which is required to energize the tonoplast for ion uptake into the vacuole, while V-PPase plays only a minor role. The increase in V-ATPase activity is not obtained by structural changes of the enzyme, but by an increase in V-ATPase protein amount.

Biological Transport, Active↗