Biomedical subjects

Wei Liu

Publications and source records attributed to Wei Liu.

At least 163 records · Page 9Linked to original sources

PubMed2006

[The influences on mandibular development after removing the outer cortex of mandibular body in childhood minitype pigs].

OBJECTIVE: To study the influences on mandibular development after removing the outer cortex of mandibular body in childhood minitype pig. METHODS: Six childhood minitype pigs were selected as the experimental animals. The outer cortex of mandibular body measured as 3.0 cm x 1.5 cm was removed in one side, and the other side remained intact as the control. The changes of mandibular modality and occlusion relationship as well as the histological and biomechanical changes were studied 24 weeks after operation. RESULTS: There was no obvious difference compared with the control side in the height of the mandibular ramus and the length of the mandibular body, However, lateral deviation occlusion was found in some animals. The body thickness was thinner than that of the control side, there were no obvious biomechanical and histological differences between the two sides. CONCLUSIONS: There was less influence on the growth of mandibular bone after removing one side of the outer cortex of the mandibular body in childhood minitype pig. But further study should be done for the cause of the lateral deviation of the mandible in part of the animals.

Animals↗

PubMed2006

[Protective effect of Uncaria rhynchophylla total alkaloids pretreatment on hippocampal neurons after acute hypoxia].

OBJECTIVE: To investigate the effect of Uncaria rhynchophylla total alkaloids (RTA) pretreatment on the voltage-gated sodium currents of the rat hippocampal neurons after acute hypoxia. METHOD: Primary cultured hippocampal neurons were divided into RTA pre-treated and non-pretreated groups. Patch clamp whole-cell recording was used to compare the voltage-gated sodium current amplitude and threshold with those before hypoxia. RESULT: After acute hypoxia, sodium current amplitude was significantly decreased and its threshold was upside. RTA pretreatment could inhibit the reduction of sodium current amplitude. CONCLUSION: RTA pretreatment alleviates the acute hypoxia-induced change of sodium currents, which may be one of the mechanisms for protective effect of RTA on cells.

Alkaloids↗

PubMed2006

[IL-10 gene modification on immature dendritic cells induces antigen-specific tolerance in experimental autoimmune myocarditis].

OBJECTIVE: To investigate whether IL-10 gene modification on immature dendritic cells (iDC) could induce autoimmune tolerance in rat experimental autoimmune myocarditis (EAM). METHODS: EAM was induced by cardiac myosin immunization on day 0 and day 7 in rats. A total of 2 x 10(6) mature DC (mDC), iDC, pcDNA3 transfected iDC, pcDNA3-IL-10 transfected iDC or PBS were injected intravenously at 5th immunization day. Three weeks later, echocardiography and HE staining were performed to observe the cardiac function and myocardial inflammation. Th1/Th2 cytokines were detected by ELISA and MHC-II molecules, costimulatory molecules were identified by flow cytometry. In vitro T lymphocyte proliferation assay and adoptive transfer of DCs were performed to determine the antigen specific tolerance induced by IL-10 gene modification on iDCs. RESULTS: EAM rats treated with pcDNA3-IL-10 transfected iDC showed improved cardiac function and reduced inflammatory cells infiltration into myocardium. Moreover, lower Th1 and higher Th2-type response was induced, MHC-II and costimulatory molecules down-regulated and antigen specific immunological responses towards cardiac myosin inhibited in pcDNA3-IL-10-iDC treated EAM rats. CONCLUSION: Treatment with IL-10 gene modified iDCs could ameliorates EAM by inducing Th2 polarization and down-regulation of MHC-II molecules and costimulatory molecule expressions.

Animals↗

PubMed2006

[Epidemiology of pediatric HIV infection in six provinces of China].

OBJECTIVE: To investigate the epidemiology of pediatric human immunodeficiency virus (HIV) infection in six provinces of China. METHODS: A cross-sectional study was conducted in six provinces with the highest HIV prevalence. Surveys on demographics and HIV-related questions (transmission modes, time of diagnosis, clinical stage, laboratory test) were distributed to clinicians in these provinces. Descriptive and bivariate analyses were performed on the completed surveys. RESULTS: Survey results of 650 children [405 males and 245 females; average age: (7.9 +/- 3.2) years] were eligible for analysis. The interval between possible transmission and diagnosis was (7.1 +/- 3.2) years. The location distribution was as follows: 570 cases (87.7%) in Henan Province, 23 cases (3.5%) in Guangxi Province, 21 cases (3.2%) in Yunnan Province, 19 cases (2.9%) in Hubei Province, 10 cases (1.5%) in Anhui Province, and 7 cases (1.1%) in Shanxi Province. Transmission routes included mother-to-child transmission (75.1%), blood transfusion/ plasma donation (15.7 %), and injecting drug use (IDU, 0.5%). Former plasma donation (FPD) was the main transmission route in some provinces (Henan, Shanxi, Hubei, and Anhui), while IDU was the main transmission route in other provinces (Guangxi and Yunnan). The average age in the FPD provinces was significantly higher than that in IDU provinces [(8.1 +/- 3.2) vs. (5.4 +/- 2.2) years, P <0.001]. Among 178 patients in all six provinces who required treatment (on the basis of CD4 count or WHO staging), 133 (74.7%) did not receive treatment and 45 (25.3%) received antiretroviral therapy. CONCLUSION: Mother-to-child transmission is the main transmission mode in pediatric patients. Efforts should be made to strengthen the diagnosis and treatment of pediatric HIV/AIDS patients.

Child↗

PubMed2006

[Pegylated interferon alpha 2a in treating chronic hepatitis B patients].

OBJECTIVE: To evaluate the efficacy and safety of pegylated interferon alpha 2a (PEG-IFN alpha-2a) in treating patients with chronic hepatitis B. METHOD: Seventy-two patients with chronic hepatitis B were assigned to a PEG-IFN alpha-2a (experimental) group (n=42) and an interferon alpha (control) group (n=30) randomly. Each patient in the experimental group received 180 microg PEG-IFN alpha-2a every week. Each patient in the control group received 500 MU interferon alpha every day. All the patients were treated for 48 weeks, and then were followed for another 48 weeks with no treatment. RESULTS: At the end of the 12th week, the rate of HBeAg negative cases was 30% in the PEG-IFN alpha-2a group, which was much higher than in the control group (x2 = 4.162, P < 0.05). The values of HBeAg and the log value of HBV DNA in the PEG-IFN alpha-2a group were much lower than the values before the treatment (t = 2.689, t = 4.080, P <0.01), but there was no difference between before and after treatment in the control group ( t = 1.229, t = 1.009, P > 0.05). At the end of the 24th week, the rate of HBeAg negative cases in the PEG-IFN alpha-2a group was much higher than that in the control group (x2=6.190, P < 0.05). The value of HBeAg and the log value of HBV DNA in the PEG-IFN alpha-2a group were much lower than in the control group (t=2.215, t=2.122, P < 0.05). At the end of the 48th week, besides the reduction mentioned above, the rate of cases with HBeAg/antiHBe seroconversion and normalization of ALT and complete responsiveness in the PEG-IFN alpha-2a group were all much higher than those in the control group (x2=5.771, x2=5.617, x2=5.308, P < 0.05). At the end of 48 weeks with no treatment, all the parameters mentioned above in the PEG-IFN alpha-2a group were much better than those in the control group and they remained so, but they were different in the control group (x2=11.943, t=3.439, t=6.111, x2=9.930, x2=9.522, x2=7.920, P < 0.01). Nine patients in the PEG-IFN alpha-2a group had liver biopsies before their treatment and also at the end of their treatment. The expressions of HBsAg and HBcAg were decreased at the end of the treatment. The rate of expression of HBsAg in the liver tissues before the treatment was 88.9% but only 22.2% at the end of the treatment (x2=8.001, P < 0.01). The rate of expression of HBcAg in the livers before treatment was 66.7% but only 33.3% at the end of the treatment. Before and at the end of the PEG-IFN alpha-2a treatment, there were no significant changes in the degrees of inflammation and fibrosis and the quantity of collagen in the liver tissues. Three patients in the PEG-IFN alpha-2a group (10%) were HbsAg negative. Two of them were found so at the end of 32 weeks with treatment and one patient was found at the end of 24 weeks with no treatment, but there were no HBsAg negative patients in the control group. The adverse reactions that occurred in the PEG-IFN alpha-2a and in the control groups were similar. CONCLUSION: PEG-IFN alpha-2a was effective in inhibiting HBV replication. The effect of PEG-IFN alpha-2a was lasting. PEG-IFN alpha-2a was well tolerated during our treatment.

Adolescent↗

PubMed2006

[Salt resistance and its mechanism of cucumber under effects of exogenous chemical activators].

With root injection and foliar spray, this paper studied the effects of different concentrations salicylic acid, brassinolide, chitosan and spermidine on the growth, morphogenesis, and physiological and biochemical characters of cucumber ( Cucumis sativus L. ) seedlings under 200 mmol x L(-1) NaCl stress. The results showed that at proper concentrations, these four exogenous chemical activators could markedly decrease the salt stress index and mortality of cucumber seedlings, and the decrement induced by 0. 01 mg x L (-1) brassinolide was the largest, being 63. 0% and 75. 0% , respectively. The activities of superoxide dismutase (SOD) , peroxidase (POD) and catalase (CAT) increased significantly, resulting in a marked decrease of malondialdehyde (MDA) content and electrolyte leakage. The dry weight water content and morphogenesis of cucumber seedlings improved, and the stem diameter, leaf number, and healthy index increased significantly. All of these suggested that exogenous chemical activators at proper concentrations could induce the salt resistance of cucumber, and mitigate the damage degree of salt stress. The salt resistance effect of test exogenous chemical activators decreased in the sequence of 0.005 -0.05 mg (L-1) brassinolide, 150 -250 mg x L (-1) spermidine, 100 -200 mg x L(-1) chitosan, and 50 -150 mg x L(-1) salicylic acid.

Brassinosteroids↗

PubMed2006

[Cold tolerance and wintering cultivation effect of different Welsh onion varieties].

With Welsh onion Zhangqiu as the contrast, this paper measured the physiological indices including electrolyte leakage, malondialdehyde content, protective enzyme activity, chlorophyll content, photosynthetic rate and root vitality of two introduced Welsh onion varieties Chunwei and Changhao, and identified their cold tolerance and wintering cultivation effect. The results showed that during wintering cultivation, all test Welsh onion varieties suffered low temperature stress, which led the electrolyte leakage and malondialdehyde content arrived at the maximum, while the chlorophyll content and photosynthetic rate dropped to the bottom at 15 January. At this time, the function data of physiological indices were 0. 452, 0. 364, and 0. 226 for Chuowei, Changbao and Zhangqiu, respectively, suggesting that Chunwei had stronger cold tolerance, followed by Changbao, and Zhangqiu. The bolting rate of Chunwei, Changbao and Zhangqiu when harvested was 0, 35.2% and 81.0% , respectively. Although the biological yield of Changbao was 25.67% and 52. 94% higher than that of Chunwei and Zhangqiu, respectively, the economic yield of Chunwei was the highest (5.49 kg m2) , with an increment of 18. 57% than Changbao, and that of Zhangqiu was only 0. 86 kg x m(-2) It could be concluded that Chonwei was fit to cultivate in low tunnel in winter, while Zhangqiu was weaker in cold tolerance and not fit to wintering cultivation.

Allium↗

PubMed2005

Effect of asymmetric distribution of phospholipids in ghost membrane from rat blood on peroxidation induced by ferrous ion.

This study used rat erythrocyte ghost membrane to investigate the effect of aminophospholipid distribution in biological membranes on oxidative susceptibility. Aminophospholipids, lipid peroxidation, and carbonyl compounds were quantified; plasma membrane structure was examined using atomic force microscopy (AFM) and SDS-polyacrylamide gel electrophoresis (SDS-PAGE). Inside-out vesicles (IOVs) had significantly more aminophospholipids and greater lipid peroxidation than right-side-out vesicles (ROVs). Spectrin bands in IOVs disappeared obviously than in ROVs as shown in SDS-PAGE. In both systems vesicle protein size increased significantly with oxidation. Proteins aggregated much more in IOVs than ROVs at 48 h. These observations suggest that IOVs were more susceptible to ferrous ion-induced peroxidation than ROVs and that asymmetric phospholipid distribution affects biomembranes' oxidative susceptibility.

Animals↗

PubMed2005

System development for multichannel electrotactile stimulation on the lips.

Multichannel pulsatile stimulation is essential for electrotactile presentation of spatiotemporal patterns in sensory substitution through the sense of touch. In this paper, a system for multichannel electrotactile stimulation is presented for studying electrotactile sensation on the lips, a site that has been shown to be highly sensitive but never been assessed for electrotactile applications. The system utilized a demultiplexing scheme to deliver voltage-clamped pulse waveforms to 32 channels corresponding to an array of 4x8 stimulators. Initial testing of electrotactile presentation on the lips was performed in human subject experiments on threshold measurement and two-line separation. For an array of hemispherical stimulators each 700 microm in diameter, the threshold values on the lower lip were averaged at only 8.2 V and intensities for well-perceived stimulation were averaged at around 14.2 V. The testing results suggested that lips were promising sites for electrotactile applications due to their high sensitivity to electrotactile stimulation at extremely low intensities.

Adult↗

PubMed2005

A novel receptor activator of NF-kappaB (RANK) cytoplasmic motif plays an essential role in osteoclastogenesis by committing macrophages to the osteoclast lineage.

Receptor activator of NF-kappaB (RANK) ligand (RANKL) and its receptor RANK play an essential role in osteoclastogenesis and osteoclast function by activating several signaling pathways. However, several lines of evidence suggest that RANK also transmits an unidentified signaling pathway(s) essential for osteoclastogenesis. To identify the novel pathway(s), we carried out a detailed structure/function study of the RANK cytoplasmic domain. A series of studies using numerous deletion/point mutants elucidated a specific 4-amino acid motif (535IVVY538) essential for osteoclastogenesis. This novel motif plays a crucial role in committing macrophages to the osteoclast lineage but is not implicated in osteoclast function or survival. Moreover, this motif does not activate the known RANK signaling pathways, indicating that it initiates a novel pathway(s). The identification of the novel motif not only provides critical insight into RANK signaling in osteoclastogenesis, but more importantly, the RANK motif and its downstream signaling pathways may represent specific therapeutic targets for various bone diseases, including postmenopausal osteoporosis.

Amino Acid Motifs↗

PubMed2005

Paradoxical increase in ventricular torsion and systolic torsion rate in type I diabetic patients under tight glycemic control.

OBJECTIVES: This study sought to characterize the early features of diabetic cardiomyopathy by magnetic resonance imaging (MRI) tagging. BACKGROUND: The earliest manifestations of diabetic cardiomyopathy have not been well established, especially under tight glycemic management. We hypothesized that torsion measurements would identify subclinical contractile alterations in type I diabetics with normal left ventricular ejection fraction, mass, blood pressure, and aggressive glycemic control. We also sought to characterize the influence of elevated resting heart rates (HRs) of diabetics on torsion. METHODS: Sixteen patients with type I diabetes and 10 control patients underwent cine and tagged MRI with a 1.5-T scanner. Torsion, strain, and their rates were measured. To quantify the influence of chronotropic and inotropic stimulation on torsion, nine healthy volunteers underwent MRI tagging at rest, after atropine injection, and after exercise. RESULTS: Diabetic patients (hemoglobin A1c, 6.8 +/- 0.4%) had a higher resting HR (77.0 +/- 12.4 beats/min vs. 59.0 +/- 5.6 beats/min; p < 0.01), higher maximal torsion by 23% (3.5 +/- 0.9 degrees/cm vs. 2.7 +/- 0.4 degrees/cm; p < 0.01) and higher maximal systolic torsion rate (TR-s) by 25% (0.013 +/- 0.003 degrees/cm/s vs. 0.010 +/- 0.002 degrees/cm/s, p = 0.01). Torsion did not significantly change with chronotropic stimulation (p = 0.30). CONCLUSIONS: In diabetics under tight glycemic control, we observed a surprising increase in torsion and TR-s unrelated to chronotropic influences of HR. We propose that increased torsion and TR-s could represent early predictive markers of the propensity to cardiac dysfunction in asymptomatic type I diabetics. Furthermore, these findings seem fundamental to the diabetic state itself and unaccounted for by other comorbidities.

Adult↗

PubMed2005

Enhanced anti-angiogenic effect of a deletion mutant of plasminogen kringle 5 on neovascularization.

Kringle 5 (K5), a proteolytic fragment of plasminogen, has been proved to be an angiogenic inhibitor. Previously, we have evaluated the effect of K5 on the vascular leakage and neovascularization in a rat model of oxygen-induced retinopathy. In this study, we expressed K5 and a deletion mutant of K5 (K5 mutant) in a prokaryocyte expression system and purified them by affinity chromatography. K5 mutant was generated by deleting 11 amino acids from K5 while retaining the three disulfide bonds. The anti-angiogenic activity of intact K5 and K5 mutant were compared in endothelial cells and retinal neovascularization rat model. K5 mutant inhibited the proliferation of primary human retinal capillary endothelial cells (HRCEC) in a concentration-dependent manner, with an apparent EC50 of approximate 35 nmol/L, which is twofold more potent than intact K5. In the even higher concentration range, K5 mutant did not inhibit pericytes from the same origin of HRCEC, which suggested an endothelial cell-specific inhibition. K5 mutant had no effect on normal liver cells and Bel7402 hepatoma cells even at high concentration range either. Intravitreal injection of the K5 and mutant in the oxygen-induced retinopathy rat model both resulted in significantly fewer neovascular tufts and nonperfusion area than controls with PBS injection, as shown by fluorescein angiography. Furthermore, K5 mutant exhibited more strong inhibition effect on neovascularization than intact K5 by quantification of vascular cells. These results suggest that this K5 deletion mutant is a more potent angiogenic inhibitor than intact K5 and may have therapeutic potential in the treatment of those disorders with neovascularization, such as solid tumor, diabetic retinopathy, age-related macular degeneration, rheumatoid arthritis, and hyperplasia of prostate.

Angiogenesis Inhibitors↗

PubMed2005

Temporal coordination of the arms during bilateral simultaneous and sequential movements in patients with chronic hemiparesis.

Upper extremity (UE) hemiparesis results in decreased movement speed and impaired coordination leading to functional limitations and disability. The effects of UE hemiparesis on bilateral functional reaching have not been studied even though most activities of daily living are bilateral tasks. We examined the characteristics of bilateral simultaneous (SIM-B) and bilateral sequential paretic-lead (SEQ-P) and nonparetic-lead (SEQ-NP) functional reaching tasks at preferred and fast speeds. Sixteen patients with chronic hemiparesis completed three bilateral reaching tasks as fast as possible. A subset of eight participants attempted to complete the tasks at both preferred and fastest possible speeds. Paretic (P) and nonparetic (NP) arms were not different from each other in movement time (MT) or peak velocity in the SIM-B condition. MT and peak velocity differed between the two arms during both SEQ tasks. P MT was shorter and NP MT longer in the SIM-B task compared to SEQ-P and SEQ-NP. The P arm MT was the shortest when moving with the NP arm in a simultaneous task compared to both P and NP lead sequential movements. Despite hemiparesis, the two arms demonstrate a temporal coupling when moving simultaneously. When attempting to move at fastest speed, P arm MT time is better when reaching before or with the NP arm than when reaching after the NP arm showing coupling to the NP limb and increased speed of movement. These coupling effects support the rationale for bilateral arm training for individuals with UE hemiparesis.

Aged↗

PubMed2005

Podophyllotoxin-loaded solid lipid nanoparticles for epidermal targeting.

The purpose of this study was to evaluate solid lipid nanoparticles as the topical carrier for epidermal targeting of podophyllotoxin (POD). The high pressure homogenization was employed to prepare drug-loaded solid lipid nanoparticles. The POD-loaded SLN stabilized by 0.5% poloxamer 188 and 1.5% soybean lecithin (P-SLN) and 2% polysorbate 80 (T-SLN) was characterized by photon correlation spectroscopy (PCS). P-SLN showed an average diameter of 73.4 nm and a zeta potential of -48.36 mV. The imaging of AFM indicated that the P-SLN had a spherical shape. DSC and X-ray diffraction analysis showed that POD was dispersed in SLN in an amorphous state. The in vitro permeation study showed that P-SLN increased the accumulative amount of POD in porcine skin 3.48 times over 0.15% tincture. But T-SLN with a diameter of 123.1 nm and a zeta potential of -17.4 mV did not show a high accumulative amount of POD when compared with P-SLN, though both P-SLN and T-SLN could avoid the systemic uptake of POD. Because of the fluorescence property of POD, fluorescence microscopy imaging was employed to visualize the penetration of POD into skin from SLN. The penetration of POD from P-SLN seemed to follow two pathways along the stratum corneum and hair follicle route. The imaging revealed that P-SLN had a strong localization of POD within epidermis. The penetration of P-SLN with low particle size into stratum corneum along the skin surface 'furrow' and the consequent controlled release of POD might lead to the epidermal targeting. P-SLN provides a good epidermal targeting effect and may be a promising carrier for topical delivery of POD.

Animals↗

PubMed2005

[Relationship of CTLA-4 exon 1 A49-->G polymorphism with sCTLA-4 and Th1/Th2 bias in idiopathic dilated cardiomyopathy].

OBJECTIVE: To investigate the association of cytotoxic T lymphocyte associated antigen-4 (CTLA-4) gene exon 1 A49-->G polymorphism with the genetic susceptibility to idiopathic dilated cardiomyopathy (IDC) in Chinese Han nationality. METHODS: Peripheral blood samples were collected from 48 patients with IDC, 31 males and 17 females, and 50 sex- and age-matched normal controls. ELISA was used to examine the cytokines: sCTLA-4, gamma-interferon (IFN-gamma), and interleukin-4 (IL-4)with the ratio of IFN-gamma/IL-4 as an indicator for Th1/Th2 bias. PCR-RFLP was used to analyze the A/G polymorphism of CTLA-4 exon 1 A49-->G. The relationship of CTLA-4 genotype and alleles frequencies with sCTLA-4, IFN-gamma and IFN-gamma/IL-4 was evaluated by linear regression analysis. RESULTS: Compared with the normal controls, the frequencies of GG genotype (0.6042 and 0.7396, P = 0.012) and the G allele (0.36 and 0.56, P = 0.008) were significantly increased in the patients with IDC. Increased serum sCTLA-4 was found in the IDC group compared with the controls (1.87 microg/L +/- 1.06 microg/L vs. 0.54 microg/L +/- 0.19 microg/L, P < 0.05). IFN-gamma was significantly lower in the IDC group than in the control group (16 ng/L +/- 6 ng/L vs. 30 ng/L +/- 10 ng/L, P < 0.05). The ratio of IFN-gamma/IL-4 was significantly in the IDC group than in the control group (1.63 +/- 0.50 vs. 3.01 +/- 0.89, P < 0.05). No statistically difference was found in the IL-4 level between the two groups. Linear regression analysis manifested significant interrelationship between the GG genotype, G allele frequencies and serum sCTLA-4 (r = 0.57, P = 0.021), IFN-gamma/IL-4 ratio (r = 0.42, P = 0.028) in the IDC group. While no correlation was found for AA, AG genotype and the A allele frequency. CONCLUSION: CTLA-4 gene exon 1 A49-->G substitution is associated with an increased IDC genetic susceptibility, which implicates that the CTLA-4 gene may have a significant role in IDC, possibly via a Thr-->Ala change in CTLA-4 signal peptide, with a result of functional change of sCTLA-4. The bias of Th1/Th2 paradigm is associated with the increased sCTLA-4 level under certain background of immunogenicity.

Antigens, CD↗

PubMed2005

Golgi inheritance in mammalian cells is mediated through endoplasmic reticulum export activities.

Golgi inheritance during mammalian cell division occurs through the disassembly, partitioning, and reassembly of Golgi membranes. The mechanisms responsible for these processes are poorly understood. To address these mechanisms, we have examined the identity and dynamics of Golgi proteins within mitotic membranes using live cell imaging and electron microscopy techniques. Mitotic Golgi fragments, seen in prometaphase and telophase, were found to localize adjacent to endoplasmic reticulum (ER) export domains, and resident Golgi transmembrane proteins cycled rapidly into and out of these fragments. Golgi proteins within mitotic Golgi haze-seen during metaphase-were found to redistribute with ER markers into fragments when the ER was fragmented by ionomycin treatment. The temperature-sensitive misfolding mutant ts045VSVG protein, when localized to the Golgi at the start of mitosis, became trapped in the ER at the end of mitosis in cells shifted to 40 degrees C. Finally, reporters for Arf1 and Sar1 activity revealed that Arf1 and Sar1 undergo sequential inactivation during mitotic Golgi breakdown and sequential reactivation upon Golgi reassembly at the end of mitosis. Together, these findings support a model of mitotic Golgi inheritance that involves inhibition and subsequent reactivation of cellular activities controlling the cycling of Golgi components into and out of the ER.

ADP-Ribosylation Factor 1↗

PubMed2005

Role of CCR5 in IFN-gamma-induced and cigarette smoke-induced emphysema.

Th1 inflammation and remodeling characterized by tissue destruction frequently coexist in human diseases. To further understand the mechanisms of these responses, we defined the role(s) of CCR5 in the pathogenesis of IFN-gamma-induced inflammation and remodeling in a murine emphysema model. IFN-gamma was a potent stimulator of the CCR5 ligands macrophage inflammatory protein-1alpha/CCL-3 (MIP-1alpha/CCL-3), MIP-1beta/CCL-4, and RANTES/CCL-5, among others. Antibody neutralization or null mutation of CCR5 decreased IFN-gamma-induced inflammation, DNA injury, apoptosis, and alveolar remodeling. These interventions decreased the expression of select chemokines, including CCR5 ligands and MMP-9, and increased levels of secretory leukocyte protease inhibitor. They also decreased the expression and/or activation of Fas, FasL, TNF, caspase-3, -8, and -9, Bid, and Bax. In accordance with these findings, cigarette smoke induced pulmonary inflammation, DNA injury, apoptosis, and emphysema via an IFN-gamma-dependent pathway(s), and a null mutation of CCR5 decreased these responses. These studies demonstrate that IFN-gamma is a potent stimulator of CC and CXC chemokines and highlight the importance of CCR5 in the pathogenesis of IFN-gamma-induced and cigarette smoke-induced inflammation, tissue remodeling, and emphysema. They also demonstrate that CCR5 is required for optimal IFN-gamma stimulation of its own ligands, other chemokines, MMPs, caspases, and cell death regulators and the inhibition of antiproteases.

Animals↗

PubMed2005

Evidence of genetic overlap of schizophrenia and bipolar disorder: linkage disequilibrium analysis of chromosome 18 in the Costa Rican population.

The long-standing concept that schizophrenia (SC) and bipolar disorder (BP) represent two distinct illnesses has been recently challenged by findings of overlap of genetic susceptibility loci for these two diseases. We report here the results of a linkage disequilibrium (LD) analysis of chromosome 18 utilizing subjects with SC from the Central Valley of Costa Rica. Evidence of association (P < 0.05) was obtained in three chromosomal regions: 18p11.31 (D18S63), 18q12.3 (D18S474), and 18q22.3-qter (D18S1161, D18S70), all of which overlap or are in close proximity with loci previously shown to be in LD with BP, type I in this population. Since both the SC and bipolar samples contained cases with a history of mania and almost all cases of SC and BP had a history of psychosis, we performed an alternative phenotyping strategy to determine whether presence or absence of mania, in the context of psychosis, would yield distinct linkage patterns along chromosome 18. To address this issue, a cohort of psychotic patients (including a range of DSMIV diagnoses) was divided into two groups based on the presence or absence of mania. Regions that showed association with SC showed segregation of association when the sample was stratified by history of mania. Our results are compared with previous genetic studies of susceptibility to SC or BP, in Costa Rica as well as in other populations. This study illustrates the importance of detailed phenotype analysis in the search for susceptibility genes influencing complex psychiatric disorders in isolated populations and suggests that subdivision of psychoses by presence or absence of past mania syndromes may be useful to define genetic subtypes of chronic psychotic illness.

Bipolar Disorder↗