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Biomedical subjects

Wei Zhou

Publications and source records attributed to Wei Zhou.

At least 181 records · Page 10Linked to original sources
PubMed2004

Structural insights into the functional interaction of KChIP1 with Shal-type K(+) channels.

Four Kv channel-interacting proteins (KChIP1 through KChIP4) interact directly with the N-terminal domain of three Shal-type voltage-gated potassium channels (Kv4.1, Kv4.2, and Kv4.3) to modulate cell surface expression and function of Kv4 channels. Here we report a 2.0 Angstrom crystal structure of the core domain of KChIP1 (KChIP1*) in complex with the N-terminal fragment of Kv4.2 (Kv4.2N30). The complex reveals a clam-shaped dimeric assembly. Four EF-hands from each KChIP1 form each shell of the clam. The N-terminal end of Kv4.2 forming an alpha helix (alpha1) and the C-terminal alpha helix (H10) of KChIP1 are enclosed nearly coaxially by these shells. As a result, the H10 of KChIP1 and alpha1 of Kv4.2 mediate interactions between these two molecules, structurally reminiscent of the interactions between calmodulin and its target peptides. Site-specific mutagenesis combined with functional characterization shows that those interactions mediated by alpha1 and H10 are essential to the modulation of Kv4.2 by KChIPs.

Animals↗
PubMed2004

Synthesis and antitumor activity of 10-substituted benzylidene anthrone.

Fifteen compounds of 10-substituted benzylidene anthrone were prepared with moderate yield by reaction of anthrone and substituted benzaldehydes under the presence of pyridine and piperidine as catalyst. Their antitumor activities in vitro were evaluated. The results show that the electron-withdrawing substitutes decrease the activities, the electron-donor substitutes increase the activities; the compound with substitute at ortho or para position has stronger activities than that of compound with the same substitute but located at the meta position. There are six compounds which appear as strong effective inhibition for A-549 cancer cell growth. This is a kind of good leading compound which is worth researching further.

Anthracenes↗
PubMed2004

MHC class I-associated presentation of exogenous peptides is not only enhanced but also prolonged by linking with a C-terminal Lys-Asp-Glu-Leu endoplasmic reticulum retrieval signal.

Vaccination with antigenic peptide-pulsed antigen-presenting cells (APC) represents an attractive approach for therapy for cancer and diseases caused by intracellular infections. It has been suggested that sufficient stable MHC/peptide complexes on the surface of APC might play an important role in the generation of antitumor and antiviral immunity in vivo. In this study, we observed that exogenous peptides that were artificially fused with an endoplasmic reticulum (ER) retrieval signal, a C-terminal Lys-Asp-Glu-Leu sequence, could be efficiently presented by intracellular MHC class I molecules in a TAP- and proteasome-independent, but brefeldin A-sensitive manner. The APC retained the capacity to display surface MHC/peptide complexes for a prolonged period. In addition, our results show that vaccination with DC bearing our fusion peptides induced greatly enhanced specific CTL response, and resulted in significant inhibition of tumor growth. Thus, the ER retrieval signal modification can be regarded as a novel method for targeting exogenous peptides into the intracellular MHC class I presentation pathway, and may improve the clinical utility of vaccines based on synthetic peptide pulsed DC.

Animals↗
PubMed2004

Two variants of the human hepatocellular carcinoma-associated HCAP1 gene and their effect on the growth of the human liver cancer cell line Hep3B.

We have cloned a cDNA from chromosome band 17p13.3, designated as HCAP1 (HCC-associated protein 1, originally named HC56). Database searches revealed that HCAP1 shares most of its open reading frame with GEMIN4. Single nucleotide polymorphism (SNP) screening revealed a high incidence of SNP in the coding region of HCAP1 (12 SNP sites). A collection of 140 controls and 22 cases from the Qidong area was genotyped at 6 SNP sites. The 22 cases exhibited higher frequencies of minor alleles than did the controls, and 2 sites revealed significant differences between the controls and the cases. We constructed 2 haplotypes, HCAP1-N (with common alleles at 5 SNP sites) and HCAP1-M (with minor alleles at 5 SNP sites), in a mammalian expression system. Both haplotypes resulted in a remarkable reduction in colony formation and suppression of cell growth after being transfected into the human hepatocellular carcinoma (HCC) cell line. The inhibitory effect of HCAP1-N was stronger than that of HCAP1-M. Different haplotypes also resulted in different gene expression profiles in the Hep3B cell line according to an examination of 588 genes on an Atlas membrane. The expression induced by HCAP1-M caused an up-regulation of genes involved in cellular proliferation and a down-regulation of genes involved in cellular apoptosis and DNA repair. These results, in addition to the statistical data, are biological evidence that the HCAP1-M variant of HCAP1 has a reduced inhibitory effect on hepatocarcinoma cell growth and an impaired DNA repair system. This suggests that HCAP1-M may be related to cancer susceptibility.

Alleles↗
PubMed2004

Anti-angiogenesis effect on glioma of attenuated Salmonella typhimurium vaccine strain with flk-1 gene.

To investigate the anti-vasculature effects and the anti-glioma effects of attenuated Salmonella typhimurium vaccine strain expressing VEGFR2 (flk-1) gene, plasmid pcDNA3.1-flk1 was constructed and electro-transfected into live attenuated Salmonella typhimurium strain SL7207. Mouse models of intracranial G1261 glioblastoma were treated with an orally administered attenuated Salmonella typhimurium expressing flk-1 gene. The survival period was recorded and vessel density was observed by immunofluorescence. CTLs activity was measured by MTT assay. Our results showed that attenuated Salmonella typhimurium vaccine strain expressing flk-1 gene could significantly inhibit glioblastoma growth, reduce vessel density, prolong the survival period and improve the survival rate in these mice. The flk-1 specific CTLs activity was increased obviously after the vaccination. Our study showed that attenuated Salmonella typhimurium vaccine strain expressing flk-1 gene could break peripheral immune tolerance a in glioma gainst this self-antigen and kill endothelial cells by the orally administered vaccine and can be used for both prophylactic and therapeutic purposes.

Angiogenesis Inhibitors↗
PubMed2004

Carotid artery stenting with routine cerebral protection in high-risk patients.

BACKGROUND: Carotid artery stenting has emerged as an alternative treatment modality in carotid occlusive disease. This study examined our experience of carotid stenting with routine cerebral embolization protection in high-risk patients. METHODS: Clinical variables and treatment outcome of high-risk patients who underwent carotid stenting with neuroprotection were analyzed during a 26-month period. RESULTS: Sixty-eight high-risk patients with 72 carotid artery stenoses were treated. Procedural success was achieved in 70 cases (97%), and symptomatic lesions existed in 17 (24%) patients. Monorail Wallstents stents were used in all cases. Neuroprotective devices used were PercuSurge (28%) and Filterwire (72%). There was no periprocedural mortality or neuroprotective device-related complications. The 30-day stroke and death rate was 2.7%, and the overall complication rate was 6.9%. All stented vessels remained patent during the follow-up period (mean 15.3 +/- 4.2, range 1 to 23 months). Two asymptomatic in-stent restenosis (3%) occurred at 6 and 8 months, which were both successfully treated with balloon angioplasty. CONCLUSIONS: Our study showed that percutaneous carotid stenting with routine use of a cerebral protection device is a feasible and effective treatment in high-risk patients with carotid occlusive disease.

Aged↗
PubMed2004

The impact of anesthetic modality on the outcome of carotid endarterectomy.

BACKGROUND: Carotid endarterectomy (CEA) reduces the risk of stroke in patients with high-grade carotid artery stenosis. This study evaluates the clinical outcome of CEA performed under local anesthesia (LA) versus general anesthesia (GA). METHODS: Clinical variables and treatment outcomes were analyzed in 548 CEAs performed under either LA or GA during a 30-month period. Factors associated with morbidity were also analyzed. RESULTS: A total of 263 CEAs under LA and 285 CEA under GA were analyzed. The LA group was associated with a lower incidence of shunt placement, operative time, and perioperative hemodynamic instability compared to the GA group. No differences in neurologic complications or mortality were found between the 2 groups. Hyperlipidemia was a risk factor for postoperative morbidity in both the LA and GA groups, while age greater than 75 years was associated with increased overall morbidity in the GA group but not the LA group. CONCLUSIONS: This study demonstrates that increased age is associated with increased morbidity in CEA under GA, while hyperlipidemia is associated with increased morbidity in CEA regardless of the anesthetic choice.

Age Distribution↗
PubMed2004

Abdominal aortic surgery in patients with human immunodeficiency virus infection.

PURPOSE: Human immunodeficiency virus (HIV) infection is known to cause acquired immune deficiency syndrome, which has been associated with a wide array of cardiovascular pathologies. This report examined the clinical outcome of patients infected with HIV who underwent abdominal aortic reconstruction for aneurysm or occlusive disease. METHODS: Hospital and clinic records of all patients with HIV infection who underwent an abdominal aortic operation were reviewed during an 11-year period. Relevant risk factors and clinical variables were assessed for surgical outcome. RESULTS: Forty-eight HIV patients (mean age 54 +/- 13 years) were identified who underwent abdominal aortic bypass grafting during the study period. Indications for aortic operation included aneurysm (n = 20) and aortoiliac occlusive disease (n = 28). All patients underwent successful aortic reconstructions without intraoperative mortality. Postoperative complications and in-hospital mortality occurred in 16 patients (33%) and 7 patients (15%), respectively. The mean follow-up period was 41 months. Life-table survival rates in aneurysm and occlusive patients at 60 months were 43.2% +/- 5.3% and 46.3% +/- 7.4% (not significant), respectively. Multivariate analysis showed that low CD4 lymphocyte counts (< 200/microL, P <0.05) and hypoalbuminemia (<3.5 g/dL, P <0.05) were risk factors for postoperative complications. CONCLUSION: Perioperative morbidity and mortality rates are high in HIV patients undergoing an abdominal aortic operation. Low CD4 lymphocyte counts and hypoalbuminemia are associated with poor clinical outcomes in HIV patients undergoing abdominal aortic reconstruction.

Adult↗
PubMed2004

Induction of P815 tumor immunity by DNA-based recombinant Semliki Forest virus or replicon DNA expressing the P1A gene.

AIM: To compare the prophylactic and therapeutic effects of alphaviruses in the same tumor model, we used a DNA-based approach to generate a replicon DNA and recombinant Semliki Forest virus (rSFV) particles expressing P1A, the P815 mastocytoma tumor associated antigen, and compared the immune effect of each vaccine. METHODS: Six to eight-week-old female DBA/2 mice were inoculated with P1A plasmid or viral vaccines. Spleen cells were assayed for antigen-specific cytotoxic T cell activity. Tumor growth or survival rate was observed in preventive and therapeutic experiments, respectively. RESULTS: We found that the rSFV particles prevented tumor growth when delivered prior to innoculation of mice with P815 cells, and more importantly, improved survival when delivered after the initiation of tumor growth. Naked P1A replicon DNA also functioned as a protective and therapeutic vaccine, although with less potency than rSFV particles. Virus particles also elicited a stronger cellular immune response as measured by target cell lysis. CONCLUSION: rSFV particles have stronger specific prophylactic and therapeutic immune effects in mice than replicon DNA-based DNA vaccines, though the latter is more effective than traditional plasmid vectors (e.g. pCI-neo vector).

Animals↗
PubMed2004

Radiation-associated venous stenosis: endovascular treatment options.

We report a case of radiation-induced venous stenosis after pelvic irradiation to treat Paget's disease of the scrotum. During therapeutic anticoagulation, significant left lower extremity swelling developed due to an iliofemoral deep venous thrombosis (DVT). After percutaneous thrombectomy and thrombolysis, a high-grade stenosis was uncovered in the left external iliac vein, which was treated with an endoluminal stent. However, ipsilateral DVT recurred 2 months later despite continued anticoagulation therapy. Repeat treatment was successful. Pelvic radiation is a potential cause of iliac vein stenosis. Pharmacomechanical thrombectomy may have a useful role in management of complex iliofemoral DVT.

Aged↗
PubMed2004

Acute arterial thrombosis associated with cocaine abuse.

PURPOSE: Cocaine-induced arterial thrombosis is uncommon, and most reported cases involved small-diameter vessels such as the cerebral and coronary arteries. This study was undertaken to review our experience with peripheral arterial thrombosis presumed caused by cocaine abuse. METHODS: Hospital records were reviewed for all patients admitted over 10 years with acute arterial occlusion involving the peripheral arterial system. Patients with confirmation of cocaine use or of its derivative, crack cocaine, within 24 hours of hospital admission formed the basis of this study. Symptoms at presentation, management, and outcome in these patients were reviewed. RESULTS: Three hundred eighty-two patients with acute peripheral arterial occlusion were identified during the study period. The presumptive diagnosis of cocaine-induced arterial occlusion was made in 5 patients (4 men, mean age 38 years). Cocaine use was achieved via intranasal inhalation in 2 patients (40%), whereas the 3 remaining patients smoked crack cocaine (60%). The mean time between cocaine use and onset of arterial thrombosis was 9.2 hours (range, 2-20 hours). Symptoms at presentation included acute limb ischemia without pedal Doppler signals (3 patients, 60%) and abdominal pain without femoral pulses (2 patients, 40%). Arterial occlusion was confirmed on angiograms in all patients, which revealed aortic thrombosis in 1 patient (20%), iliac thrombosis in 2 patients (40%), superficial femoral artery thrombosis in 1 patient (20%), and popliteal artery occlusion in 1 patient (20%). Surgical thrombectomy was successfully performed in 4 patients (80%), and 1 patient (20%) underwent successful thrombolytic therapy for femoropopliteal artery occlusion. There was no perioperative mortality. All 5 patients who were discharged were available for follow-up (mean, 36 months; range, 6-75 months). There was 1 late death from myocardial infarction. In 1 patient recurrent lower extremity arterial thrombosis developed after 28 months, which was successfully treated with thrombolytic therapy. CONCLUSIONS: Our study underscores cocaine abuse as a potential cause of acute arterial thrombosis. Cocaine-induced arterial thrombosis should be suspected in patients with recent history of cocaine abuse with acute limb ischemia without an identifiable source or overt cardiovascular risk factors. Prompt angiography with operative or endovascular intervention should be performed to avert arterial ischemic sequelae.

Adult↗
PubMed2004

Pharmacomechanical thrombectomy for treatment of symptomatic lower extremity deep venous thrombosis: safety and feasibility study.

PURPOSE: The current standard of care for deep venous thromboembolism (DVT) is anticoagulation; however, this treatment method does not rapidly relieve clot burden or clinical symptoms. We describe a rapid and effective method of thrombus removal, with simultaneous percutaneous mechanical thrombectomy (PMT) and thrombolysis. METHODS: Over 26 months 20 patients (22 men, 2 women; mean age, 52 +/- 6 years [range, 38-79 years]) with extensive lower extremity DVT were treated with PMT with the AngioJet thrombectomy device in combination with lytic agent (urokinase, tissue plasminogen activator, or reteplase) added to the infusion. Three patients underwent treatment twice, because of recurrent DVT. The primary end point was angiographic evidence of restoration of venous patency at completion of the procedure. Complications, recurrent ipsilateral DVT, and improvement in clinical symptoms were evaluated. RESULTS: Complete thrombus removal was obtained in 15 procedures (65%), and partial resolution in the remaining 8 procedures (35%). Inciting occlusive lesions responsible for acute DVT were revealed in 14 patients (61%), and angioplasty with or without stenting was performed when necessary. In the 8 procedures with partial resolution additional catheter-directed thrombolysis was carried out on average for 5.7 hours, with further thrombus reduction. Overall, immediate (<24 hours) improvement in clinical symptoms was noted in 17 patients (74%). There were no complications related to either PMT or the short duration of lytic agent infusion. At average follow-up of 10.2 +/- 0.3 months (range, 3-26 months), 3 patients had recurrent ipsilateral DVT, and underwent repeat treatment. CONCLUSIONS: Addition of lytic agent to PMT facilitates thrombus extraction, decreases overall interventional treatment time, and improves patient outcomes. In addition, definitive management of underlying anatomic lesions can be performed in the same setting. Further outcome measures are necessary to study the long-term efficacy of this treatment method on preservation of valve function, reduction of chronic venous insufficiency, and improved quality of life.

Adult↗
PubMed2004

Identification of a S100 calcium-binding protein expressed in HL-60 cells treated with all-trans retinoic acid by two-dimensional electrophoresis and mass spectrometry.

To characterize the alteration of protein expression during tumor cell differentiation induced by all-trans retinoic acid (ATRA) and to understand downstream signaling and molecular mechanism of ATRA action, we compared the protein expression profiles in HL-60 cells with ATRA treatment using two-dimensional electrophoresis (2-DE). Although many changes in protein expression were found in 2-DE maps, here we identified two protein spots remarkably expressed in the differentiated cells by nanoelectrospray ionization mass spectrometry and database searching. These two protein spots were found to be the same protein, namely S100 calcium-binding protein A9 (S100A9). Further study will be done to ascertain whether S100A9 plays a role in the regulation of differentiation or just a consequence of differentiation.

Calgranulin B↗
PubMed2004

Allelic variations in gene expression.

PURPOSE OF REVIEW: Genetic variants determine phenotypic variability. Many genetic studies suggest that protein structural variations predispose the population to more than 1000 different hereditary diseases. Unfortunately, despite the study of genetic polymorphisms for many decades, the milder phenotypic variations believed to account for most human physical and behavioral differences and underlying the most common human genetic diseases (including cancers) cannot be accounted for easily by these variations in the protein coding sequences. Thus, it has been hypothesized that the study of natural differential expression presenting within and among populations may enhance understanding of human phenotypic variation. RECENT FINDINGS: During the last year, reports identifying variations in gene expression in different organisms and finding subtle changes of gene expression associated with common genetic disease have pointed to variations in gene expression as playing a central role in molecular evolution and human disease. Advances in the functional analysis of gene regulatory networks-in particular, new methods for distinguishing cis-acting components from trans-acting factors-have provided the impetus for these discoveries. SUMMARY: This review represents current knowledge about allelic variation in gene expression and its increasingly important role in understanding the genotype-phenotype relation. Characterization of these allelic variations may open largely uncharted territory in genomics for biomedical researchers and may eventually lead to the discovery of the causative genes of common hereditary diseases and their mechanism of action.

Alleles↗
PubMed2004

Developing an OSTE to address lapses in learners' professional behavior and an instrument to code educators' responses.

PURPOSE: To develop an instrument for measuring medical educators' responses to learners' lapses in professional behavior. METHOD: In 1999, at the Indiana University School of Medicine, a 22-item checklist of behaviors was developed to describe common responses used by educators responding to learners' lapses in professional behavior. Four medical students were trained to portray lapses in professional behaviors. These students and seven clinical observers trained to categorize behaviors as present or absent. Interrater reliability was assessed during 18 objective structured teaching evaluations (OSTEs). Videotaped OSTEs were coded twice at a one-month interval for test-retest reliability. Items were classified as low, moderate, or high inference behaviors. Script realism and educator effectiveness were assessed. RESULTS: Educators rated OSTE scripts as realistic. Raters observed an average of 6 +/- 2 educator behaviors in reaction to learners' lapses in professional behavior. Educators' responses were rated as moderately effective. More experienced educators attempted more interventions and were more effective. Agreement was high among raters (86% +/- 7%), while intraclass correlation coefficients decreased with increasing inference level. From videotaped OSTEs, raters scored each behavior identically 86% of the time. CONCLUSIONS: Accurate feedback on educators' interactions in addressing learners' professionalism is essential for faculty development. Traditionally, educators have felt that faculty's responses to learners' lapses in professional behavior were difficult to observe and categorize. These data suggest that educators' responses to learners' lapses in professional behavior can be defined and reliably coded. This work will help provide objective feedback to faculty when engaging learners about lapses in professional behavior.

Education, Medical↗
PubMed2004

AMCXO and its test system.

In this paper, we introduce a novel temperature compensated crystal oscillator--analog memory compensated crystal oscillator (AMCXO), a microcomputer compensated crystal oscillator (MCXO) based on an analogue approach, and we compare the performance between MCXO and AMCXO, and analyze the necessity of developing AMCXO. Both AMCXO and MCXO, combined with their test systems, use computers to generate the control signals used for the compensated crystal oscillators according to temperature variation. However, the execution devices are much different from each other in the practical temperature compensated crystal oscillators. A MCXO uses a set of digital units, including a microprocessor, to realize the compensation. For it, equations or tables are used to express the relationship between the control signal and temperature. An AMCXO uses an analogue memory, which has the same functions as the digital units of MCXO. For AMCXO, a curve or figure based on the equations or tables is used to express the same relationship. Their test systems have obvious distinctions in temperature experiment, data acquisition, and processing. A better performance will be obtained by using a more complicated AMCXO test system, and the cost can be reduced at the same time.

Journal Article↗
PubMed2004

Clinical use and molecular mechanisms of action of extract of Ginkgo biloba leaves in cardiovascular diseases.

Ginkgo biloba is one of the oldest living tree species that has been referred to as a living fossil. Extract from Ginkgo biloba leaves (GBE) is among the most commonly used herbal drugs and is popularized for its alleged tonic effect and possible curative and restorative properties. There is an increasing evidence of the potential role of GBE in treating cardiovascular diseases. We examined the history of GBE usage and reviewed the literature on its effects on the cardiovascular system. In the extensive studies involving cell cultures and animal models, GBE has been shown to exert its action through diverse mechanisms. GBE has been reported to have antioxidatant properties, to modify vasomotor function, to reduce adhesion of blood cells to endothelium, to inhibit activation of platelets and smooth muscle cells, to affect ion channels, and to alter signal transduction. In addition, relevant clinical trials with CBE are being carried out, particularly in the treatment of arterial and venous insufficiency and in the prevention of thrombosis. Finally, the controversial clinical findings and the possible adverse interactions between GBE and other drugs are discussed. This review underscores the potential benefits of Ginkgo biloba in cardiovascular diseases, highlights the gaps in our current research, and suggests the necessity for more rigorous systematic investigation of cardiovascular properties of CBE.

Animals↗