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1.
Zhonghua Wai Ke Za Zhi ; 62(3): 223-228, 2024 Mar 01.
Artigo em Chinês | MEDLINE | ID: mdl-38291638

RESUMO

Objective: To compare the application effect of domestic and imported intravenous radiofrequency closure system in the treatment of primary varicose veins of lower extremities. Methods: This single-center prospective, non-inferiority randomized controlled trial was performed in the Department of Vascular Surgery, the Fourth Affiliated Hospital, Zhejiang University School of Medicine from January 2021 to January 2022. Patients with primary varicose veins of lower extremities who met the ataxation criteria were randomly assigned to the experimental group(domestic novel venous radiofrequency closure system) or the control group(imported venous radiofrequency closure system) in a ratio of 1∶1. The two groups of subjects were compared in terms of target vein closure rate, technical success rate, system operation performance, incidence of adverse events and incidence of serious adverse events(SAE) within 6 months after surgery. Quantitative data were compared by Mann-Whitney U test, and categorical data were compared by χ2 test and non-inferiority test. Results: A total of 80 subjects were included in the trial (41 in the experimental group and 39 in the control group), including 27 males and 53 females, aged (M(IQR)) 55(23) years (range:40 to 78 years). There were 48 cases of left lower limb and 32 cases of right lower limb. The technical success rate and system control performance between the groups were 100%.The incidence of adverse events (58.5% (24/41) vs. 61.5% (24/39), χ2=0.075, P=0.784), and the incidence of SAE (7.3% (3/41) vs. 5.1% (2/39), χ2=0.163, P=0.686) within 6 months after surgery in experimental group and control group had no statistical significance. There was one device-related adverse event in each of the two groups. In the experimental group, one patient developed endovenous heat-induced thrombosis after surgery and recovered after taking rivaroxaban tablets. One patient in the control group had pain in the upper right thigh for more than 1 day after operation, which was cured after using analgesic cream. No device-related SAE occurred. The venous closure rate of the experimental group was 100% (38/38) at 6 months after surgery, and that of the control group was 97.4% (37/38). The difference between the two groups was 2.63% (95%CI:-3.19 to 8.45, Z=4.865, P<0.01), and the 95%CI lower limit of the difference in target venous closure rate between two groups was greater than the non-inferiority threshold of -10.00%. Conclusion: The early application effect of the new domestic intravenous radiofrequency closure system in patients with primary varicose veins of lower extremities is in line with expectations, it is not inferior to the imported system.


Assuntos
Varizes , Insuficiência Venosa , Feminino , Humanos , Masculino , China , Estudos Prospectivos , Veia Safena/cirurgia , Resultado do Tratamento , Varizes/cirurgia , Insuficiência Venosa/cirurgia , Adulto , Pessoa de Meia-Idade , Idoso
2.
Mol Biol (Mosk) ; 56(4): 564-573, 2022.
Artigo em Russo | MEDLINE | ID: mdl-35964313

RESUMO

Rab GTPases are major regulators of membrane trafficking. Proteome profiling reveals dozens of Rab proteins associated with lipid droplets (LDs), but few of them have been functionally validated. Cell death activator CIDE-3 protein mediates LD fusion and growth. It is highly enriched at LD-LD contact sites. Here, we investigated the role of Rab3D in lipid storage in adipocyte. We verified that the adipose levels of Rab3D transcript were higher than that of other Rab3 family members; the differences were most pronounced in white adipose tissue. Moreover, we showed that Rab3D promotes LD growth in 3T3-L1 preadipocytes in a dose dependent manner, independently of the process of CIDE-3-mediated LD fusion. Finally, we confirmed that the GTP-bound form of Rab3D is its LD promoting form; it translocates from other vesicles to LDs during adipocyte differentiation. By contrast, the Rab3D-GDP form is retained in the cytoplasm and has no effect on LD sizes. Presented results provide evidence for the role of Rab3D in controlling formation of large LDs in adipocytes. We conclude that Rab3D is a novel LD regulator with characteristics differing from these of previously identified LD associated Rab proteins, such as Rab18 and Rab8a.


Assuntos
Adipócitos , Gotículas Lipídicas , Células 3T3-L1 , Animais , Guanosina Trifosfato , Camundongos
3.
Zhonghua Liu Xing Bing Xue Za Zhi ; 43(8): 1282-1287, 2022 Aug 10.
Artigo em Chinês | MEDLINE | ID: mdl-35981991

RESUMO

Objective: To compare the detection rate of advanced neoplasia and the number of people needing endoscopy in colorectal cancer screening giving at different starting age in population at high risk. Methods: Based on the screening project of early diagnosis and treatment of colorectal cancer in Jiashan county, Zhejiang province, two rounds of colorectal cancer screening were conducted between January 2007 and December 2020. After excluding participants who were not at high risk or had incomplete information, 27 130 participants and 31 205 participants were finally enrolled in round one and in round two, respectively. The spline analysis based on the generalized additive model was used to describe the trend of detection rate of advanced neoplasia with age. The detection rate and number of people needing endoscopy for the groups with starting age at 50, 45 and 40 years were calculated, and the differences in the detection rate were tested by χ2 goodness of fit test. Results: A total of 21 077 (77.69%) participants in round one and 25 249 (80.91%) participants in round two received endoscopy, in whom 1 097 (detection rate=52.05‰) and 1 151 (detection rate=45.59‰) had advanced neoplasia (cancers and advanced adenomas), respectively. The detection rate increased significantly with age, and the detection rate in round one were significantly higher than that in round two (P<0.05). The overall detection rates of advanced neoplasia for the groups with starting age at 50, 45 and 40 years were 61.11‰, 56.14‰ and 52.05‰ in round one, and 49.10‰, 46.75‰ and 45.59‰ in round two, respectively. The rates were significantly higher for the group with starting age at 50 years than that with starting age at 40 years in both round one and round two (P<0.05). The numbers of people needing endoscopy of advanced neoplasia for the groups with starting age at 50, 45 and 40 years were 17, 18, and 20 in round one, and 21, 22 and 22 in round two. Conclusions: The detection rate of advanced neoplasia increased with age. Starting screening at lower age might contribute to decreased detection rate and increased number of people needing endoscopy. However, the difference was limited.


Assuntos
Neoplasias Colorretais , Detecção Precoce de Câncer , Adulto , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/epidemiologia , Humanos , Programas de Rastreamento , Pessoa de Meia-Idade , Sangue Oculto
4.
Zhonghua Liu Xing Bing Xue Za Zhi ; 42(7): 1188-1193, 2021 Jul 10.
Artigo em Chinês | MEDLINE | ID: mdl-34814529

RESUMO

Objective: To explore the association between sleep duration, sleep quality and the prevalence of hypertension in the elderly aged 65 years and above. Methods: This study was conducted among the elderly in communities in Yiwu, China from April to July, 2019, and participants were recruited through physical examination in the hospital. Face-to-face interview was performed to obtain basic information. Sleep duration and sleep quality were evaluated by Pittsburgh Sleep Quality Index (PSQI). Associations between sleep duration, sleep quality and hypertension were evaluated by multivariate logistic regression analysis. Results: A total of 3 169 elderly persons, aged ≥65 years old, were included in the study. The overall prevalence of hypertension was 50.8%. The elderly with very poor sleep quality and short sleep duration accounted for 22.4% and 28.5%, respectively. After adjusting for demographic characteristics, socioeconomic status, lifestyle and health status, the OR of hypertension for the elderly with very poor sleep quality was 1.42 (95%CI: 1.12-1.80) compared with those with very good sleep quality. Compared with the elderly with sleep duration of 6-7 h a night, the OR of hypertension for those with sleep duration <6 h was 1.37 (95%CI: 1.15-1.65). As the sleep quality decreased, the risk for hypertension increased. An U-shaped association was found between sleep duration and risk of hypertension. Subgroup analyses showed that this association existed in both men and women, but only significant in the elderly aged <75 years. Conclusion: Poor sleep quality and short sleep duration were associated with risk for hypertension in the elderly.


Assuntos
Hipertensão , Transtornos do Sono-Vigília , Idoso , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Hipertensão/epidemiologia , Masculino , Prevalência , Fatores de Risco , Sono , Transtornos do Sono-Vigília/epidemiologia
5.
Zhonghua Liu Xing Bing Xue Za Zhi ; 41(10): 1649-1654, 2020 Oct 10.
Artigo em Chinês | MEDLINE | ID: mdl-33297621

RESUMO

Objective: To explore the association between lifestyle-related factors and colorectal adenoma. Methods: Based on the Screening Project of Early Diagnosis and Treatment of Colorectal Cancer in Jiashan county Zhejiang province, from August 2012 to March 2018, information gathered through records on questionnaire and colonoscopic diagnosis were collected from participants with positive results during the primary screening stage. According to the findings of colonoscopy, 11 232 controls without any colorectal diseases and 3 895 cases with colorectal adenoma were included in the study. Multivariate logistic regression models were used to analyze the association between lifestyle-related factors and colorectal adenoma. Results: After adjusting for possible confounding factors, results from multivariate logistic regression analysis showed that smoking, alcohol drinking and obesity were positively related to the risk of colorectal adenoma, with ORs (95%CIs) as 1.38 (1.24-1.54), 1.37 (1.24-1.51) and 1.38 (1.20-1.59) respectively. However, regular aspirin intake was negatively related with the risk of colorectal adenoma (OR=0.65, 95%CI: 0.53-0.80). After stratified by sex and age, data showed that the associations between smoking, alcohol drinking and colorectal adenoma were statistically significant in males, and the association between regular aspirin intake and colorectal adenoma was also statistically significant in older participants (aged 60 years and older). Conclusion: Smoking, alcohol drinking, regular aspirin intake and obesity were associated with colorectal adenoma.


Assuntos
Adenoma , Neoplasias Colorretais , Estilo de Vida , Adenoma/epidemiologia , Idoso , China/epidemiologia , Colonoscopia , Neoplasias Colorretais/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco
6.
Zhonghua Liu Xing Bing Xue Za Zhi ; 41(10): 1662-1667, 2020 Oct 10.
Artigo em Chinês | MEDLINE | ID: mdl-33297623

RESUMO

Objective: To evaluate the impact of colonoscopy on the incidence of colorectal cancer (CRC). Methods: This study was based on the Screening Project of Early Diagnosis and Treatment of CRC in Jiashan county, Zhejiang province. After excluding participants with incomplete information, these with individual history of CRC, those with CRC, enteritis or ulcer, noticed through colonoscopy exam at baseline, a total of 25 894 participants were finally included. Cox proportional hazards regression model was used to analyze the association between colonoscopy and the incidence of CRC. Results: This study was followed up for 160 113 person-years with a median of 5.67 years. During the follow-up period, 127 of them developed the CRC. The incidence rates of CRC in participants, were 202.35 per 100 000 person-years, 40.93 per 100 000 person-years and 63.62 per 100 000 person-years, respectively among the following three groups: who did not take the colonoscopy, without colorectal lesions or with benign colorectal lesions noticed by the colonoscopy and the differences were statistically significant (P<0.05). After adjusting for potential confounding factors, the HRs(95%CI) of CRC were 0.24 (0.16-0.36) and 0.29 (0.17-0.49), among those who did not have or had colorectal lesions in the participants who underwent the colonoscopy. Stratified by anatomic site, age and sex, results showed that the associations among the aforementioned groups were relatively stable. Conclusion: Colonoscopy could effectively contribute to the reduction of CRC incidence in the high-risk population.


Assuntos
Colonoscopia , Neoplasias Colorretais , Idoso , China/epidemiologia , Colonoscopia/estatística & dados numéricos , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/prevenção & controle , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Medição de Risco
7.
Phys Chem Chem Phys ; 19(28): 18505-18513, 2017 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-28682363

RESUMO

The motion of liquid metal has potential applications ranging from micro-pumps and self-fueled motors to rapid cooling and drug delivery. In this study, we systematically investigate the effects of the radius of LMDs (liquid metal droplets), the concentration of electrolyte solution and the applied electric field on the movement behavior of LMDs experimentally. The research also explains the experimental phenomenon with an innovative modeling analysis, which combines pertinent forces (i.e., the driving force induced by the gradient of surface tension, the viscous friction between the droplet and its surrounding electrolyte, and the friction between the droplet and the substrate). The model is highly consistent with the rule that LMDs with a larger radius need smaller actuation voltage, and we can predict the critical voltages of LMDs with r = 2-4 mm through Velectrode = 30.62/r2 - 0.998, which is obtained by fitting the parameters. We also obtain the model V = [-66.2Vr2/(259.7-17.7) + 1.253]r2, which can predict the average velocity-voltage lines of LMDs with r = 3, 3.5 mm and V = 1-13 V. In addition, the velocity increases upon increasing the concentration of the electrolyte solution from 0.1 mol L-1 to 0.3 mol L-1, and tends to be stable at more than 0.3 mol L-1 owing to the saturation of the EDL (electrical double layer) charge density. Additionally, we discuss the phenomenon of elongation during movement that occurs upon increasing the size of the LMDs. If the size of the LMDs continues to increase, the reverse movement from the anode to the cathode can occur, and the phenomenon can also be explained by the model.

8.
Zhonghua Liu Xing Bing Xue Za Zhi ; 38(6): 772-778, 2017 Jun 10.
Artigo em Chinês | MEDLINE | ID: mdl-28647981

RESUMO

Objective: This study aimed to describe the sex disparities on cancer incidence and mortality in Jiashan population. Methods: All data concerning incident and death cases of cancers were gathered from the database of Cancer Registry in Jiashan county. Data from the 2010 China census was used as the standard population. Sex-specific age-standardized incidence rates (ASIRs), mortality rates (ASMRs) per 100 000 persons for all cancers and types of each cancer were calculated for the years of 1990 to 1999, 2000 to 2009, 2010 to 2014, and 1990 to 2014. In addition, the corresponding male-to-female incidence rate ratios (IRRs) and mortality rate ratios (MRRs) were also calculated. Results: The ASIR of all cancers was 226.13/10(5) for the whole period of 1990 to 2014, with 266.04/10(5) for males and 187.22/10(5) for females, respectively. The corresponding IRR was 1.42 (95%CI: 1.39-1.46), with significant difference noticed in the incidence rates between males and females (P<0.05). The ASMR of all cancers was 155.39/10(5), with 206.55/10(5) for males and 104.98/10(5) for females, respectively. The corresponding MRR was 1.97 (95% CI: 1.91-2.03), with significant difference between males and females (P<0.05). Among all the cancer types, only gallbladder cancer and thyroid cancer showed female predominance in both incidence and mortality, with male predominance in all the remaining cancers. Conclusion: Finding from our study suggested that a male predominance in both incidence and mortality for a majority of cancers in Jiashan population.


Assuntos
Neoplasias/etnologia , Neoplasias/mortalidade , Sistema de Registros , China/epidemiologia , Bases de Dados Factuais , Feminino , Neoplasias da Vesícula Biliar/etnologia , Neoplasias da Vesícula Biliar/mortalidade , Humanos , Incidência , Masculino , Padrões de Referência , Distribuição por Sexo , Fatores Sexuais , Taxa de Sobrevida , Neoplasias da Glândula Tireoide/etnologia , Neoplasias da Glândula Tireoide/mortalidade
9.
Zhonghua Liu Xing Bing Xue Za Zhi ; 38(1): 65-68, 2017 Jan 10.
Artigo em Chinês | MEDLINE | ID: mdl-28100379

RESUMO

Objective: To evaluate the cost-effectiveness of colorectal cancer screening program in different age groups from the view of health economics. Methods: The screening compliance rates, detection rates in different age groups were calculated by using the data from colorectal cancer screening program in Jiashan county, Zhejiang province. The differences in indicator among age groups were analyzed with χ(2) test or trend χ(2) test. The ratios of cost to the number of case were calculated according to cost statistics. Results: The detection rates of immunochemical fecal occult blood test (iFOBT) positivity, advanced adenoma and colorectal cancer and early stage cancer increased with age, while the early diagnosis rates were negatively associated with age. After exclusion the younger counterpart, the cost-effectiveness of individuals aged >50 years could be reduced by 15%-30%. Conclusion: From health economic perspective, it is beneficial to start colorectal cancer screening at age of 50 years to improve the efficiency of the screening.


Assuntos
Neoplasias Colorretais/diagnóstico , Programas de Rastreamento/economia , Sangue Oculto , Avaliação de Processos e Resultados em Cuidados de Saúde/economia , Idoso , Neoplasias Colorretais/economia , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/prevenção & controle , Análise Custo-Benefício , Detecção Precoce de Câncer , Feminino , Humanos , Masculino , Programas de Rastreamento/métodos , Pessoa de Meia-Idade , Avaliação de Programas e Projetos de Saúde
10.
Zhonghua Liu Xing Bing Xue Za Zhi ; 38(12): 1713-1715, 2017 Dec 10.
Artigo em Chinês | MEDLINE | ID: mdl-29294593

RESUMO

Epidemiology is one of main courses for undergraduate students majoring in preventive medicine. There are some limitations in the traditional epidemiology teaching, which is usually characterized in indoctrinated education: "lectured by the teachers and listened by the students." In Zhejiang University, staff of the epidemiology division tried to explore a new teaching mode as 'student-centered, teacher-leading, question-based, and combining with literature discussion and course practice.' After practicing for two years, students were inspired in learning initiatives, with teaching effectiveness obviously improved.


Assuntos
Currículo , Epidemiologia/educação , Medicina Preventiva/educação , Ensino , Humanos , Universidades
11.
Mol Carcinog ; 51 Suppl 1: E21-31, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21976437

RESUMO

To explore the associations of SNPs within hsa-miR-605 (rs2043556) and hsa-miR-149 (rs2292832) and lifestyle-related factors with gastrointestinal cancer, a case-control study including 762 cases and 757 controls was conducted. Marginally significant associations were found both for hsa-miR-149 rs2292832 with gastric cancer risk (TC + CC vs. TT, OR = 0.68, 95% CI: 0.44-1.04) and for hsa-miR-605 rs2043556 with colorectal cancer risk (AG + GG vs. AA, OR = 0.70, 95% CI: 0.48-1.02) in males. Tea drinking showed a protective effect on gastric cancer risk (OR = 0.28, 95% CI: 0.13-0.60), while smoke inhalation increased the risk of gastric cancer (OR = 1.94, 95% CI: 1.08-3.47). Irritability was found to be a risk factor for both colorectal cancer (OR = 1.61, 95% CI: 1.02-2.53) and gastric cancer (OR = 1.96, 95% CI: 1.17-3.29). Among those that engaged in smoke inhalation, miR-149 CT/CC and miR-605 AG/GG genotype carriers had increased susceptibilities to colorectal cancer (OR = 1.90, 95% CI: 1.11-3.25) and gastric cancer (OR = 1.87, 95% CI: 1.03-3.42), respectively. Among the tea drinkers, there exists a marginally protective effect of miR-605 AG/GG genotypes on colorectal cancer incidence (OR = 0.71, 95% CI: 0.47-1.06) and a significantly protective effect of miR-149 CT/CC on gastric cancer incidence (OR = 0.47, 95% CI: 0.29-0.77). The SNPs of rs2292832 and rs2043556 might be able to modify the susceptibility to male gastric and colorectal cancers, respectively. Tea drinking is a protective factor, while smoke inhalation is a risk factor for gastric cancer, and they might have the potential to modify the associations between miR-149 and miR-605 polymorphisms with gastrointestinal cancer risk. In addition, irritability was shown to be a risk factor for both gastric and colorectal cancers.


Assuntos
Neoplasias Gastrointestinais/genética , Predisposição Genética para Doença , MicroRNAs , Polimorfismo de Nucleotídeo Único , Idoso , Estudos de Casos e Controles , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/genética , Feminino , Expressão Gênica , Humanos , Humor Irritável , Estilo de Vida , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Fumar , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/genética , Chá
12.
J Virol ; 73(3): 1828-34, 1999 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-9971760

RESUMO

A number of human immunodeficiency type 1 (HIV-1)-based vectors have recently been shown to transduce nondividing cells in vivo as well as in vitro. However, if these vectors are to be considered for eventual clinical use, a major consideration is to reduce the probability of unintended generation of replication-competent virus. This can be achieved by eliminating viral genetic elements involved in the generation of replication-competent virus without impairing vector production. We have designed a system to transiently produce HIV-1-based vectors by using expression plasmids encoding Gag, Pol, and Tat of HIV-1 under the control of the cytomegalovirus immediate-early promoter. Our data show that the best vector yield is achieved in the presence of the Rev/Rev-responsive element (RRE) system. However, the constitutive transport element of Mason-Pfizer monkey virus can substitute for RRE and Rev at least to some extent, whereas the posttranscriptional regulatory element of human hepatitis B virus appeared to be inefficient. In addition, we show that high-titer virus preparations can be obtained in the presence of sodium butyrate, which activates the expression of both the packaging construct and the vector genome. Finally, our results suggest that efficient infectivity of vectors defective in the accessory proteins Vif, Vpr, Vpu, and Nef depends on the nature of the target cells.


Assuntos
Terapia Genética , Vetores Genéticos , HIV-1/genética , Transfecção , Ácido Butírico/farmacologia , HIV-1/fisiologia , Células HeLa , Humanos , Montagem de Vírus
13.
AJR Am J Roentgenol ; 164(2): 343-6, 1995 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-7839966

RESUMO

OBJECTIVE: The purpose of this article is to report the finding of transient focal increased attenuation of the liver adjacent to the gallbladder on enhanced CT scans in patients with acute cholecystitis. This finding should not be confused with primary liver abnormalities. MATERIALS AND METHODS: Five patients with acute cholecystitis were studied. Because a thickened gallbladder wall was seen on sonography, all patients were examined preoperatively with incremental dynamic helical CT to exclude carcinoma of the gallbladder. CT findings were compared with results of sonography for five patients, MR imaging for two patients, and surgery for five patients. RESULTS: Transient focal increased attenuation of the liver adjacent to the gallbladder was seen in the early phase of incremental dynamic CT in five patients and extended into the medial segment anterior to the porta hepatis. The areas showing increased attenuation adjacent to the gallbladder had a curvilinear shape around the gallbladder. No hepatic masses were seen on sonograms, on MR images, or at surgery. CONCLUSION: Transient focal increased attenuation of the liver may occur on CT scans in patients with acute cholecystitis. The increased attenuation associated with acute cholecystitis has a typical location and pattern. This finding is probably attributable to hepatic arterial hyperemia and to early venous drainage caused by the adjacent inflamed gallbladder. This finding should be differentiated from hypervascular hepatic tumors.


Assuntos
Colecistite/diagnóstico por imagem , Fígado/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Doença Aguda , Idoso , Diagnóstico Diferencial , Feminino , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Masculino , Fatores de Tempo , Ultrassonografia
14.
J Virol ; 68(12): 8454-60, 1994 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-7966642

RESUMO

Many African primates are known to be naturally infected with simian immunodeficiency viruses (SIVs), but only a fraction of these viruses has been molecularly characterized. One primate species for which only serological evidence of SIV infection has been reported is the yellow baboon (Papio hamadryas cynocephalus). Two wild-living baboons with strong SIVAGM seroreactivity were previously identified in a Tanzanian national park where baboons and African green monkeys shared the same habitat (T. Kodama, D. P. Silva, M. D. Daniel, J. E. Phillips-Conroy, C. J. Jolly, J. Rogers, and R. C. Desrosiers, AIDS Res. Hum. Retroviruses 5:337-343, 1989). To determine the genetic identity of the viruses infecting these animals, we used PCR to examine SIV sequences directly in uncultured leukocyte DNA. Targeting two different, nonoverlapping genomic regions, we amplified and sequenced a 673-bp gag gene fragment and a 908-bp env gene fragment from one of the two baboons. Phylo-genetic analyses revealed that this baboon was infected with an SIVAGM strain of the vervet subtype. These results provide the first direct evidence for simian-to-simian cross-species transmission of SIV in the wild.


Assuntos
Chlorocebus aethiops/virologia , Transmissão Vertical de Doenças Infecciosas/veterinária , Papio/virologia , Filogenia , Reação em Cadeia da Polimerase/métodos , Síndrome de Imunodeficiência Adquirida dos Símios/transmissão , Vírus da Imunodeficiência Símia/genética , Vírus da Imunodeficiência Símia/patogenicidade , Proteínas do Envelope Viral , Sequência de Aminoácidos , Animais , Animais Selvagens , Sequência de Bases , Primers do DNA , DNA Viral/sangue , Feminino , Genes env , Genes gag , Genoma Viral , Proteína gp120 do Envelope de HIV/genética , Leucócitos/virologia , Glicoproteínas de Membrana/genética , Dados de Sequência Molecular , Proteínas dos Retroviridae/genética , Homologia de Sequência de Aminoácidos , Vírus da Imunodeficiência Símia/isolamento & purificação
15.
EMBO J ; 13(12): 2935-47, 1994 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-8026477

RESUMO

Elucidation of the phylogenetic origins of simian and human immunodeficiency viruses (SIV and HIV) is fundamental to the understanding of HIV pathogenesis and the spread of AIDS worldwide. In this study, we molecularly characterized multiple SIVAGM isolates from four different African green monkey species (vervet, grivet, sabaeus and tantalus monkeys). Phylogenetic analysis of partial (1 kb) env sequences indicated that all SIVAGM strains cluster together, and that they fall into four distinct sequence sub-groups according to their species of origin. However, alignment of long terminal repeat sequences revealed that SIVs from West African sabaeus monkeys contain a structural feature (a duplication of the transactivation response element) thus far only found in otherwise highly divergent lentiviruses infecting sooty mangabeys (SIVSM) and humans (HIV-2). To determine whether there were additional similarities with the SIVSM/HIV-2 group, a full-length replication competent sabaeus provirus was cloned and sequenced. In phylogenetic trees derived from the central and 3' coding regions, the sabaeus virus clustered with SIVAGM isolates from other African green monkey species. However, in trees derived from the 3' half of gag and the adjacent 5' region of pol, the sabaeus virus grouped with the SIVSM/HIV-2 lineage. These results indicated that the sabaeus virus comprised a mosaic genome which must have resulted from recombination of divergent lentiviruses in the distant past. A second, independent sabaeus isolate exhibited similar phylogenetic relationships, suggesting that all West African green monkey viruses share this complex evolutionary history. Taken together, these results indicate that African green monkeys have been infected with SIVAGM for very long periods of time, and that recombination and cross-species transmission in the wild have contributed to the genetic complexity of primate lentiviruses.


Assuntos
Chlorocebus aethiops/microbiologia , Genoma Viral , Recombinação Genética , Síndrome de Imunodeficiência Adquirida dos Símios/microbiologia , Vírus da Imunodeficiência Símia/genética , África Ocidental/epidemiologia , Sequência de Aminoácidos , Animais , Sequência de Bases , Evolução Biológica , Chlorocebus aethiops/classificação , Genes env/genética , Variação Genética , Dados de Sequência Molecular , Filogenia , Provírus/genética , RNA Viral/genética , Sequências Repetitivas de Ácido Nucleico/genética , Homologia de Sequência de Aminoácidos , Homologia de Sequência do Ácido Nucleico , Síndrome de Imunodeficiência Adquirida dos Símios/epidemiologia , Vírus da Imunodeficiência Símia/classificação , Especificidade da Espécie
16.
Biochem J ; 294 ( Pt 2): 511-5, 1993 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-8373365

RESUMO

The function of the immunophilins, FKBP 12 and FKBP 13, which are binding proteins for the immunosuppressant drug FK506 and rapamycin, remains poorly defined, although it has been suggested that immunophilins and immunophilin-like proteins may play a role in protein sorting/folding and intracellular calcium ion regulation. As a first step towards understanding the function of FKBP 13, we studied its subcellular localization by immunoblotting of well-defined subcellular fractions from a canine pancreatic homogenate and immunocytochemical analysis of an overexpressed cloned cDNA for FKBP 13. Whereas FKBP 12 fractionated entirely into the cytosol, virtually all FKBP 13 was found in the rough microsomal fraction which consisted of highly purified rough endoplasmic reticulum (ER), along with several well-characterized ER markers [the immunoglobulin heavy-chain binding protein (BiP), grp 94 and ribophorin I]. Moreover, FKBP 13 co-banded with the ER markers on isopycnic sucrose gradients. By immunofluorescence, the overexpressed cDNA for FKBP 13 in Hela cells gave an ER-staining pattern highly similar to that of known ER proteins. Addition of the ligand FK506 did not appear to alter the distribution of FKBP 13. Separation of the ER luminal contents and membrane revealed FKBP 13 to be a luminal ER protein. Since the lumen of the ER is where the folding of membrane and secreted proteins occurs, as well as a major site of intracellular calcium storage, it seems possible that FKBP 13 may be involved in one of these functions.


Assuntos
Proteínas de Transporte/análise , Retículo Endoplasmático/química , Proteínas de Choque Térmico/análise , Pâncreas/ultraestrutura , Sequência de Aminoácidos , Animais , Sequência de Bases , Proteínas de Transporte/química , Proteínas de Transporte/genética , Centrifugação Isopícnica , DNA/análise , DNA/genética , Cães , Imunofluorescência , Deleção de Genes , Genes myc , Células HeLa , Proteínas de Choque Térmico/química , Proteínas de Choque Térmico/genética , Humanos , Immunoblotting , Imuno-Histoquímica , Dados de Sequência Molecular , Mutagênese , Proteínas Recombinantes/química , Proteínas Recombinantes/metabolismo , Proteínas de Ligação a Tacrolimo , Transfecção
17.
J Virol ; 66(6): 3971-5, 1992 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-1583738

RESUMO

To investigate the glycoprotein determinants of viral cytopathology, we constructed chimeric env genes between a noncytopathic strain of human immunodeficiency virus type 2 (HIV-2), designated HIV-2/ST, and a highly fusogenic and cytopathic variant derived from this virus. Expression of the resulting chimeric glycoproteins indicated that efficient syncytium formation in the human T-cell line Sup T1 mapped to the C-terminal region of the transmembrane (TM) glycoprotein subunit. In this region, the wild-type and cytopathic ST glycoproteins differed by only four amino acids and by the presence of a premature termination codon in the cytopathic variant. Subsequent site-directed mutagenesis indicated that the cytoplasmic domain truncation was responsible for the enhanced fusion activity. This modification, however, increased the fusion activity of the glycoprotein only in Sup T1 cells (in which the ST variant arose) but not in Molt 4 clone 8 or peripheral blood mononuclear cells. These observations indicate that the length of the cytoplasmic domain of the HIV-2 glycoprotein modulates the fusion activity of the exterior glycoprotein complex in a cell-specific manner. Such adaptability appears to permit the emergence of fusogenic variants during HIV-2 passage in vitro and may also regulate viral growth or cytopathic effects in selected cell types during natural infection in vivo.


Assuntos
Fusão Celular/efeitos dos fármacos , Produtos do Gene env/farmacologia , Infecções por HIV/patologia , HIV-2/patogenicidade , Linfócitos T/patologia , Sequência de Aminoácidos , Sequência de Bases , Linhagem Celular , Análise Mutacional de DNA , Produtos do Gene env/biossíntese , Produtos do Gene env/genética , Vetores Genéticos/genética , Células Gigantes/microbiologia , Células Gigantes/patologia , Humanos , Dados de Sequência Molecular , Proteínas Recombinantes de Fusão/biossíntese , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/farmacologia , Relação Estrutura-Atividade , Linfócitos T/microbiologia , Vaccinia virus/genética
18.
Proc Natl Acad Sci U S A ; 88(5): 1903-7, 1991 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-2000394

RESUMO

We report the cloning and characterization of a cDNA encoding a second human cyclosporin A-binding protein (hCyPB). Homology analyses reveal that hCyPB is a member of the cyclophilin B (CyPB) family, which includes yeast CyPB, Drosophila nina A, and rat cyclophilin-like protein. This family is distinguished from the cyclophilin A (CyPA) family by the presence of endoplasmic reticulum (ER)-directed signal sequences. hCyPB has a hydrophobic leader sequence not found in hCyPA, and its first 25 amino acids are removed upon expression in Escherichia coli. Moreover, we show that hCyPB is a peptidyl-prolyl cis-trans isomerase which can be inhibited by cyclosporin A. These observations suggest that other members of the CyPB family will have similar enzymatic properties. Sequence comparisons of the CyPB proteins show a central, 165-amino acid peptidyl-prolyl isomerase and cyclosporin A-binding domain, flanked by variable N-terminal and C-terminal domains. These two variable regions may impart compartmental specificity and regulation to this family of cyclophilin proteins containing the conserved core domain. Northern blot analyses show that hCyPB mRNA is expressed in the Jurkat T-cell line, consistent with its possible target role in cyclosporin A-mediated immunosuppression.


Assuntos
Isomerases de Aminoácido/genética , Proteínas de Transporte/genética , Família Multigênica , Sinais Direcionadores de Proteínas/genética , Isomerases de Aminoácido/metabolismo , Sequência de Aminoácidos , Sequência de Bases , Proteínas de Transporte/metabolismo , Linhagem Celular , Clonagem Molecular , Endotélio Vascular/enzimologia , Escherichia coli/genética , Biblioteca Gênica , Humanos , Cinética , Dados de Sequência Molecular , Sondas de Oligonucleotídeos , Peptidilprolil Isomerase , Reação em Cadeia da Polimerase , Homologia de Sequência do Ácido Nucleico
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