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Biomedical subjects

Fei Wang

Publications and source records attributed to Fei Wang.

At least 109 records · Page 6Linked to original sources
PubMed2004

Anterior cingulum abnormalities in male patients with schizophrenia determined through diffusion tensor imaging.

OBJECTIVE: This study used diffusion tensor imaging to examine fractional anisotropy in the anterior cingulum and posterior cingulum bundles in patients with schizophrenia. METHOD: Twenty-one male patients and 20 healthy comparison men were studied. RESULTS: Reduced fractional anisotropy was seen for both sides of the anterior cingulum in the schizophrenia patients, who also exhibited less left-greater-than-right asymmetry in the anterior cingulum than was seen in the comparison subjects. CONCLUSIONS: The findings suggest structural disconnections in the anterior cingulum in patients with schizophrenia.

Analysis of Variance↗
PubMed2004

Awareness about factors that affect the management of hypertension in Puerto Rican patients.

INTRODUCTION: There are few published reports describing the health status of Hispanic populations in the United States with chronic illnesses, such as hypertension. Most studies on hypertension in Hispanics are on Mexican-Americans and little data exist for other Hispanic subgroups, such as Puerto Ricans. Health-related issues specific to a particular Hispanic subgroup may not be generalizable to all Hispanics. Patients' perceptions and awareness of health-related issues specific to a particular medical condition play an important role in the management and outcome. OBJECTIVE: The primary objective of the study is to determine if patients' general perceptions of hypertension, hypertension-related risk factors, complications, and life-style behavior modifications correlated with various patient demographics, such as age, gender, primary language, education level, socioeconomic status, marital status, health insurance category, and employment status. The working hypothesis is that patients who are older, unmarried, less educated, Spanish-speaking only, unemployed, and have low income, are more likely to report lack of awareness to various hypertension-related issues. SETTING: Hospital-based ambulatory center with major emphasis on providing care to underserved populations of the surrounding community, of which Puerto Ricans comprised the predominant ethnic group. STUDY DESIGN: A single, bilingual interviewer administered a series of questions to Hispanic, hypertensive patients. Questions were divided into the following seven categories: patient knowledge and perception of the disease; diet and salt intake; tobacco use; alcohol use; weight control and exercise; and medication and alternative therapy use. Within each category were various questions designed to study the patients' knowledge of hypertension, self-reported compliance with behavior modifications, and patient education on these behaviors. Data from 19 Puerto Rican patients were collected and chi-square tests and pothoc power analyses were performed. Responses to the various questions were correlated to patient demographics and socioeconomic variables. RESULTS: Use of herbal teas correlated significantly with the patients' primary language. Twenty-one percent of the patients who spoke Spanish only used herbal teas for treatment of their hypertension. All patients who reported herbal medication or tea use had a middle school education. There were many trends towards statistical significance in the following categories: patient perceptions and level of formal education; patient knowledge of hypertension and language spoken; salt intake and years of schooling; and correlation of herbal use with employment status, health insurance statu, and age. CONCLUSION: Additional research must be undertaken with larger sample sizes to give validity and statistical significance to the observed findings. This study and previous research, demonstrate some of the special issues that may need to be considered in the delivery of health care to specific Hispanic patient populations.

Adult↗
PubMed2004

[Expression of Notch1 gene in the differentiation of the human embryonic neural stem cells to neurons].

AIM: To explore the expression and role of Notch1 gene in the differentiation of the human embryonic neural stem cells to neurons induced by all-trans-retinoic-acid(ATRA). METHODS: The human embryonic neural stem cells were induced with various concentrations of ATRA(0.5, 1, 5 and 10 mumol/L) in vitro. Immunofluorescence staining was performed after seven days, and neurons were quantified by counting NSE positive cells. Then human embryonic neural stem cells were induced to differentiate with 1 mumol/L ATRA. Total RNA was extracted from the cells before inducing, induced for 3 days, and for 7 days. The expression of Notch1 gene was tested by semi-quantitative RT-PCR. RESULTS: The ratio of neural stem cells to differentiate to neurons was improved greatly by ATRA induction as compared with control group (P<0.01). 1 mumol/L ATRA was the optimal dose for induction of the human embryonic neural stem cell differentiation. The percentage of neurons induced by 1 micromol/L ATRA was (29.20+/-1.09)%. The expression of Notch1 gene decreased significantly after being treated with ATRA(P<0.001). CONCLUSION: ATRA can greatly increase the percentage of neurons in the course of inducing the human embryonic neural stem cells to differentiate. Notch1 gene is down-regulated when human embryonic neural stem cells differentiate into neurons.

Brain↗
PubMed2004

Human monoclonal antibodies that neutralize anthrax toxin by inhibiting heptamer assembly.

A panel of human anti-anthrax protective antigen IgG1 monoclonal antibodies were evaluated to determine the mechanism of toxin neutralization. AVP-22G12, AVP-1C6 and AVP-21D9 bound to the protective antigen with picomolar affinities to distinct non-overlapping linear epitopes. Two of the antibodies neutralized the anthrax toxin by completely inhibiting the protective antigen oligomer assembly process in vitro.

Antibodies, Monoclonal↗
PubMed2003

Regulated conformation of myosin V.

We have found that myosin V, an important actin-based vesicle transporter, has a folded conformation that is coupled to inhibition of its enzymatic activity in the absence of cargo and Ca(2+). In the absence of Ca(2+) where the actin-activated MgATPase activity is low, purified brain myosin V sediments in the analytical ultracentrifuge at 14 S as opposed to 11 S in the presence of Ca(2+) where the activity is high. At high ionic strength it sediments at 10 S independent of Ca(2+), and its regulation is poor. These data are consistent with myosin V having a compact, inactive conformation in the absence of Ca(2+) and an extended conformation in the presence of Ca(2+) or high ionic strength. Electron microscopy reveals that in the absence of Ca(2+) the heads and tail are both folded to give a triangular shape, very different from the extended appearance of myosin V at high ionic strength. A recombinant myosin V heavy meromyosin fragment that is missing the distal portion of the tail domain is not regulated by calcium and has only a small change in sedimentation coefficient, which is in the opposite direction to that seen with intact myosin V. Electron microscopy shows that its heads are extended even in the absence of calcium. These data suggest that interaction between the motor and cargo binding domains may be a general mechanism for shutting down motor protein activity and thereby regulating the active movement of vesicles in cells.

Animals↗
PubMed2003

Initiation of mucin-type O-glycosylation in dictyostelium is homologous to the corresponding step in animals and is important for spore coat function.

Like animal cells, many unicellular eukaryotes modify mucin-like domains of secretory proteins with multiple O-linked glycans. Unlike animal mucin-type glycans, those of some microbial eukaryotes are initiated by alpha-linked GlcNAc rather than alpha-GalNAc. Based on sequence similarity to a recently cloned soluble polypeptide hydroxyproline GlcNAc-transferase that modifies Skp1 in the cytoplasm of the social ameba Dictyostelium, we have identified an enzyme, polypeptide alpha-N-acetylglucosaminyltransferase (pp alpha-GlcNAc-T2), that attaches GlcNAc to numerous secretory proteins in this organism. Unlike the Skp1 GlcNAc-transferase, pp alpha-GlcNAc-T2 is predicted to be a type 2 transmembrane protein. A highly purified, soluble, recombinant fragment of pp alpha-GlcNAc-T2 efficiently transfers GlcNAc from UDP-GlcNAc to synthetic peptides corresponding to mucin-like domains in two proteins that traverse the secretory pathway. pp alpha-GlcNAc-T2 is required for addition of GlcNAc to peptides in cell extracts and to the proteins in vivo. Mass spectrometry and Edman degradation analyses show that pp alpha-GlcNAc-T2 attaches GlcNAc in alpha-linkage to the Thr residues of all the synthetic mucin repeats. pp alpha-GlcNAc-T2 is encoded by the previously described modB locus defined by chemical mutagenesis, based on sequence analysis and complementation studies. This finding establishes that the many phenotypes of modB mutants, including a permeability defect in the spore coat, can now be ascribed to defects in mucin-type O-glycosylation. A comparison of the sequences of pp alpha-GlcNAc-T2 and the animal pp alpha-GalNAc-transferases reveals an ancient common ancestry indicating that, despite the different N-acetylhexosamines involved, the enzymes share a common mechanism of action.

Acetylglucosamine↗
PubMed2003

Abnormal anterior cingulum in patients with schizophrenia: a diffusion tensor imaging study.

Diffusion tensor imaging (DTI) can non-invasively examine the molecular diffusion of water in vivo and directly reflects the anatomical integrity of neural fibers in white matter. Fractional anisotropy (FA) can be calculated from DTI data, and utilized to evaluate white matter integrity. DTI was performed on 30 patients with schizophrenia and 19 healthy controls, and their FA values were subsequently measured in multiple brain regions. Statistical analyses revealed that FA values were decreased in the anterior cingulum of schizophrenia subjects. There were no significant differences between patients and controls in any other regions. This study supports the hypothesis that schizophrenia is associated with abnormal white matter integrity of the anterior cingulum.

Adult↗
PubMed2003

A diffusion tensor imaging study of middle and superior cerebellar peduncle in male patients with schizophrenia.

Many studies have confirmed that the cerebellum takes part in higher-order cognitive coordination; profound fibers projecting to and from the cerebellum underlie its cognitive function. Since the superior and middle cerebellar peduncles are the main pathways of neural fibers in the cerebellum, these structures became the focus of our interest in evaluating the cognitive dysfunction reported in schizophrenia. Diffusion tensor imaging (DTI) was used to examine the anatomical integrity of the neural fibers in the superior and middle cerebellar peduncles. DTI was performed on 29 patients and 20 normal controls; we subsequently calculated the fractional anisotropy and mean diffusivity in these regions. Statistical analysis revealed that there was no significant difference between patients with schizophrenia and our matched control group. No structural abnormalities were detected in the white matter of the superior and middle cerebellar peduncles.

Adult↗
PubMed2003

Divergent signals and cytoskeletal assemblies regulate self-organizing polarity in neutrophils.

Like neutrophilic leukocytes, differentiated HL-60 cells respond to chemoattractant by adopting a polarized morphology, with F-actin in a protruding pseudopod at the leading edge and contractile actin-myosin complexes at the back and sides. Experiments with pharmacological inhibitors, toxins, and mutant proteins show that this polarity depends on divergent, opposing "frontness" and "backness" signals generated by different receptor-activated trimeric G proteins. Frontness depends upon Gi-mediated production of 3'-phosphoinositol lipids (PI3Ps), the activated form of Rac, a small GTPase, and F-actin. G12 and G13 trigger backness signals, including activation of a second GTPase (Rho), a Rho-dependent kinase, and myosin II. Functional incompatibility causes the two resulting actin assemblies to aggregate into separate domains, making the leading edge more sensitive to attractant than the back. The latter effect explains both the neutrophil's ability to polarize in uniform concentrations of chemoattractant and its response to reversal of an attractant gradient by performing a U-turn.

Cell Polarity↗
PubMed2003

Functional divergence of human cytoplasmic myosin II: kinetic characterization of the non-muscle IIA isoform.

Cytoplasmic (or non-muscle) myosin II isoforms are widely expressed molecular motors playing essential cellular roles in cytokinesis and cortical tension maintenance. Two of the three human non-muscle myosin II isoforms (IIA and IIB) have been investigated at the protein level. Transient kinetics of non-muscle myosin IIB showed that this motor has a very high actomyosin ADP affinity and slow ADP release. Here we report the kinetic characterization of the non-muscle myosin IIA isoform. Similar to non-muscle myosin IIB, non-muscle myosin IIA shows high ADP affinity and little enhancement of the ADP release rate by actin. The ADP release rate constant, however, is more than an order of magnitude higher than the steady-state ATPase rate. This implies that non-muscle myosin IIA spends only a small fraction of its ATPase cycle time in strongly actin-bound states, which is in contrast to non-muscle myosin IIB. Non-muscle myosin II isoforms thus appear to have distinct enzymatic properties that may be of importance in carrying out their cellular functions.

Actins↗
PubMed2003

Neck length and processivity of myosin V.

Myosin V is an unconventional myosin that transports cargo such as vesicles, melanosomes, or mRNA on actin filaments. It is a two-headed myosin with an unusually long neck that has six IQ motifs complexed with calmodulin. In vitro studies have shown that myosin V moves processively on actin, taking multiple 36-nm steps that coincide with the helical repeat of actin. This allows the molecule to "walk" across the top of an actin filament, a feature necessary for moving large vesicles along an actin filament bound to the cytoskeleton. The extended neck length of the two heads is thought to be critical for taking 36-nm steps for processive movements. To test this hypothesis we have expressed myosin V heavy meromyosin-like fragments containing 6IQ motifs, as well as ones that shorten (2IQ, 4IQ) or lengthen (8IQ) the neck region or alter the spacing between 3rd and 4th IQ motifs. The step size was proportional to neck length for the 2IQ, 4IQ, 6IQ, and 8IQ molecules, but the molecule with the altered spacing took shorter than expected steps. Total internal reflection fluorescence microscopy was used to determine whether the heavy meromyosin IQ molecules were capable of processive movements on actin. At saturating ATP concentrations, all molecules except for the 2IQ mutant moved processively on actin. When the ATP concentration was lowered to 10 microm or less, the 2IQ mutant demonstrated some processive movements but with reduced run lengths compared with the other mutants. Its weak processivity was also confirmed by actin landing assays.

Actins↗
PubMed2003

Evaluation of [Co(gly)3]- as a 35Cl- NMR shift reagent for cellular studies.

We studied the efficacy of the tris-glycinatocobaltate(II) complex ([Co(gly)(3)](-)) as a shift reagent (SR) for chloride by (35)Cl NMR spectroscopy and compared to that of Co(2+)((aq)). Due to the relatively low thermodynamic stability of [Co(gly)(3)](-), a 1:3 Co(II)/gly stoichiometric solution at physiological pH is approximately a 2:1 mixture of [Co(gly)(2)(H(2)O)(2)] and [Co(gly)(H(2)O)(4)](+). This SR was found to be stable up to higher pH values than Co(2+)((aq)), better preventing Co(OH)(2) formation at alkaline pH. No significant differences in the (35)Cl(-) NMR chemical shift induced by Co(II)/gly or Co(2+)((aq)) were observed in the presence of physiological concentrations of either Ca(2+) or Mg(2+), or of either Na(+) or K(+). Although Co(2+)((aq)) was almost twice as effective as Co(II)/gly in shifting the (35)Cl(-) NMR resonance at the same high rho ([SR]/[Cl(-)]) value and low ionic strength, Co(2+)((aq)) showed a significant decrease (p < 0.05) in the (35)Cl(-) chemical shift at higher ionic strength. Line widths at half-height were significantly (p < 0.05) less for Co(II)/gly than for Co(2+)((aq)) at rho values in the range 0.066-0.40. Intracellular chloride was clearly detectable by (35)Cl NMR spectroscopy in human skin fibroblast cells suspended in medium containing 40 mM Co(II)/gly SR. We determined that, although Co(2+)((aq)) provides a larger shift than Co(II)/gly at the same rho value, there are significant advantages for using Co(II)/gly, such as pH stability, ionic strength independent chemical shifts, narrow (35)Cl(-) NMR resonances, and reduced cellular toxicity, as a SR in biological systems.

Cells, Cultured↗
PubMed2003

Kinetic mechanism of non-muscle myosin IIB: functional adaptations for tension generation and maintenance.

Besides driving contraction of various types of muscle tissue, conventional (class II) myosins serve essential cellular functions and are ubiquitously expressed in eukaryotic cells. Three different isoforms in the human myosin complement have been identified as non-muscle class II myosins. Here we report the kinetic characterization of a human non-muscle myosin IIB subfragment-1 construct produced in the baculovirus expression system. Transient kinetic data show that most steps of the actomyosin ATPase cycle are slowed down compared with other class II myosins. The ADP affinity of subfragment-1 is unusually high even in the presence of actin filaments, and the rate of ADP release is close to the steady-state ATPase rate. Thus, non-muscle myosin IIB subfragment-1 spends a significantly higher proportion of its kinetic cycle strongly attached to actin than do the muscle myosins. This feature is even more pronounced at slightly elevated ADP levels, and it may be important in carrying out the cellular functions of this isoform working in small filamentous assemblies.

Actins↗
PubMed2003

Rac and Cdc42 play distinct roles in regulating PI(3,4,5)P3 and polarity during neutrophil chemotaxis.

Neutrophils exposed to chemoattractants polarize and accumulate polymerized actin at the leading edge. In neutrophil-like HL-60 cells, this asymmetry depends on a positive feedback loop in which accumulation of a membrane lipid, phosphatidylinositol (PI) 3,4,5-trisphosphate (PI[3,4,5]P3), leads to activation of Rac and/or Cdc42, and vice versa. We now report that Rac and Cdc42 play distinct roles in regulating this asymmetry. In the absence of chemoattractant, expression of constitutively active Rac stimulates accumulation at the plasma membrane of actin polymers and of GFP-tagged fluorescent probes for PI(3,4,5)P3 (the PH domain of Akt) and activated Rac (the p21-binding domain of p21-activated kinase). Dominant negative Rac inhibits chemoattractant-stimulated accumulation of actin polymers and membrane translocation of both fluorescent probes and attainment of morphologic polarity. Expression of constitutively active Cdc42 or of two different protein inhibitors of Cdc42 fails to mimic effects of the Rac mutants on actin or PI(3,4,5)P3. Instead, Cdc42 inhibitors prevent cells from maintaining a persistent leading edge and frequently induce formation of multiple, short lived leading edges containing actin polymers, PI(3,4,5)P3, and activated Rac. We conclude that Rac plays a dominant role in the PI(3,4,5)P3-dependent positive feedback loop required for forming a leading edge, whereas location and stability of the leading edge are regulated by Cdc42.

Actins↗
PubMed2003

Photoactivated isomerization of linear olefins.

The photocatalyzed (350 nm) isomerization of linear olefins catalyzed by platinum(II) bis(acetylacetonato) [Pt(acac)(2)] in the presence of silanes was studied. Catalytic activity depends on the silane. Triphenylsilane is the most reactive silane studied, with more than 98% isomerization of the alkene occurring after 20-min irradiation. There is no concomitant hydrosilylation. The mechanism has been investigated and a metal hydride addition-elimination mechanism proposed.

Journal Article↗
PubMed2003

Insulin glargine: a systematic review of a long-acting insulin analogue.

BACKGROUND: Insulin glargine is the first long-acting basal insulin analogue indicated for subcutaneous administration once daily at bedtime in adults with type 1 or type 2 diabetes mellitus and pediatric patients aged > or = 6 years with type 1 diabetes. It differs in structure from native human insulin by 3 amino acids, a structural modification that provides a delayed onset of action and a constant, peakless effect that has a duration of at least 24 hours. OBJECTIVE: The goal of this article was to help determine the current place in therapy of insulin glargine by reviewing all available efficacy and tolerability data published since its introduction onto the market. METHODS: Relevant English-language articles were identified through searches of MEDLINE, PubMed, and EMBASE from 1966 to October 2002 and PREMEDLINE for November 2002. The search terms used were insulin, analogs, analogues, diabetes mellitus, glargine, HOE901, HOE-901, efficacy, safety, comparative study, treatment outcome, and case report. The reference lists of the identified articles were searched for additional relevant publications. Pharmacokinetic and pharmacodynamic data were reviewed and summarized. All large clinical trials (> or = 100 patients) evaluating the efficacy and tolerability of insulin glargine in patients with type 1 or type 2 diabetes were included in the review. Studies were compared in terms of their designs, primary and secondary efficacy parameters (glycosylated hemoglobin [HbA(1c)], fasting plasma glucose [FPG] and/or fasting blood glucose [FBG] level, incidence of hypoglycemia), and tolerability assessments. RESULTS: Fourteen trials met the criteria for inclusion in this review, 7 of them published only in abstract form. All were multicenter, randomized, open-label, parallel-group trials conducted in Europe or the United States, and ranged in duration from 4 to 52 weeks. They compared insulin glargine with neutral protamine Hagedorn (NPH) insulin given once or twice daily in >5000 patients with type 1 or type 2 diabetes, or in insulin-naive patients with type 2 diabetes that was poorly controlled by oral antidiabetic agents. Insulin doses were individually titrated to achieve a target FBG level < or =120 mg/dL (6.7 mmol/L). The studies were typically statistically underpowered to detect a significant difference in HbA(1c) between treatment groups; only 3 trials were of an adequate size to have 90% statistical power to detect a mean 0.5% difference in HbA(1c). Furthermore, analysis of the data from these trials was associated with a number of methodologic problems relating to inconsistencies in reporting. Given these limitations, the available data suggest that insulin glargine treatment produces statistically significant reductions in FPG or FBG levels at end point both compared with baseline and compared with NPH insulin (P < 0.001) without achieving overall significant improvements in HbA(1c) values. However, a recent abstract of a small 52-week trial in patients with type 1 diabetes reported a 0.4% additional decrease in HbA(1c) with insulin glargine treatment compared with NPH insulin. Patients have reported greater treatment satisfaction with insulin glargine compared with NPH insulin. The findings varied regarding weight gain, overall incidence of hypoglycemia, and incidence of nocturnal hypoglycemia. Currently, the cost of insulin glargine is twice that of NPH insulin on a per-unit basis. CONCLUSIONS: As a basal insulin replacement, insulin glargine administered once daily demonstrates a steady time-action profile over 24 hours without a pronounced peak. Based on the evidence from published clinical trials, insulin glargine appears to have equal clinical efficacy to NPH insulin, produces similar reductions in HbA(1c), and is associated with lower FPG and FBG levels and a consistent and significant reduction in the incidence of nocturnal hypoglycemia in patients with type 2 diabetes.

Clinical Trials as Topic↗