AIM:To observe the structural basis of ocular motility abnormalities in patients with congenital fibrosis of the extraocular muscles type Ⅰ ( CFEOM Ⅰ) due to missense mutations in the developmental kinesin KIF21A using high - resolution magnetic resonance imaging ( MRI) .
METHODS: Totally 11 affected individuals reported KIF21A mutations were correlated with MRI studies demonstrating extraocular muscles ( EOMs ) size, location, contractility, and innervation. EOMs and the motor nerve in the orbits were imaged with T1 weighted in a triplanar scan using a dual-phased coils with 2. 0mm thick. Motor nerves were imaged at the brainstem using head coils and 3D-FIESTA with 0. 6-mm thick.
RESULTS: Patients with CFEOM Ⅰ exhibited different degrees of hypoplasia of oculomotor nerve, the abducens nerve and the trochlear nerve were also affected, of which 8 cases of orbital section could see the signal of abnormal nerve dominated by oculomotor nerve to lateral rectus. The both sides of six EOMS in all patients exhibited variable atrophy and abnormal bright internal signal on T1 imaging, particularly severe for the superior rectus and levator muscles.
CONCLUSION: High - resolution MRI can directly demonstrate pathology of motor nerves,affected EOMs, and ‘Pulley' hypoplasia caused by CFEOM Ⅰ due to mutations in KIF21A,and these findings suggest that the neuronal hypoplasia is the etiological factor of CFEOM.

The study aims to investigate the associations of SUMO4 polymorphisms with tacrolimus concentrations in Chinese renal transplant recipients. Blood samples and clinical data were collected from 132 renal transplant recipients with tacrolimus treatment. CYP3A5*3 genotypes were detected by PCR-RFLP, and SUMO4 (rs237024, rs237025) genotypes were detected by Sequenom® MassARRAY system. SUMO4 rs237024 and rs237025 genotypes were in complete linkage disequilibrium (D' = 1). The dose-adjusted concentration of tacrolimus in SUMO4 rs237024A-rs237025A (GA-GA +AA-AA) carriers was considerably higher than that in GG-GG carriers (P < 0.05). After stratification by CYP3A5*3 genotypes, SUMO4 rs237024A-rs237025A carriers (GA-GA+AA-AA) had a higher dose-adjusted tacrolimus concentration than that in GG carriers in CYP3A5 expresser (P < 0.05). The results illustrated that SUMO4 rs237024 and rs237025 polymorphisms were associated with tacrolimus concentrations, and the test of these genotypes may be useful for individualized medicine of tacrolimus.
Asian Continental Ancestry Group ; genetics ; Cytochrome P-450 CYP3A ; genetics ; Genotype ; Humans ; Immunosuppressive Agents ; blood ; therapeutic use ; Kidney ; Kidney Transplantation ; Linkage Disequilibrium ; Polymorphism, Single Nucleotide ; Small Ubiquitin-Related Modifier Proteins ; genetics ; Tacrolimus ; blood ; therapeutic use

OBJECTIVETo compare the effectiveness of immunofluorescence and polymerase chain reaction (PCR) in detecting human papilloma virus (HPV) in condyloma acuminata (CA).

METHODSHPVs in CA tissues from 60 patients were detected by immunofluorescence and PCR, respectively. Different subtypes of HPVs were also identified with restriction fragment length polymorphism (RFLP).

RESULTSThe positive detective rates of immunofluorescence and PCR were 56.67% (34/60) and 96.67% (58/ 60), respectively (P < 0.01). RFLP results showed HPV6 and HPV11 were the main subtypes in the detected virus, which accounted for 98.28%.

CONCLUSIONThe sensibility of PCR is superior to that of immunofluorescence.

Condylomata Acuminata ; virology ; Female ; Human papillomavirus 11 ; genetics ; isolation & purification ; Human papillomavirus 6 ; genetics ; isolation & purification ; Humans ; Male ; Microscopy, Fluorescence ; Polymerase Chain Reaction

Objective To establish and evaluate criteria applied to review of complete blood counts (CBC)and differential results from automated hematology analyzers.Methods Temporary criteria were established by using alarm system of XE-2100 automated hematology analyzer and by consulting the 41 suggested rides of international consensus group.2 795 out-and in-patient samples were run as clinical samples.Stained blood films were prepared and manual differential with smear review were performed on all samples.Statistical analysis was done for each temporary rule and instrument flag which indicated abnormal cell quantity and morphology.Results Of all rules,instrument flags of ‘Immature Gran/Left Shift?’, ‘ Atypical Lympho?’and‘NRBC(nucleated red blood cell)?’showed most frequent false positive and false negative instrument flag.Evaluation on rnles about cell quantity change showed false positive and false negative rates were both low.Results of morphology evaluation showed that true positive rate was 17.44%, false positive rate was 15.82%,true negative rate was 63.49%,false negative rate was 3.25%.‘ Atypical Lymphocyte?’,‘Immature Gran?’and‘blast?’were the most frequent false positive flags.According to those results and clinicians opinions,our hematology review criteria for action following automated CBC and leukocytes differential was established.Conclusions The hematology review criteria have high true positive rate and low false negative rate.To clinical hematology laboratory using automated hematology analyzer,new criteria can reduce work load,bring lower false negative rate and higher work efficiency.

OBJECTIVETo study the effects of insulin on the proteolysis of cultured rabbit skeletal muscular myotubes in vitro, and their possible mechanisms.

METHODSMuscles of lower limbs of juvenile rabbits were isolated for tissue-block culture. After passage, myoblasts were formed and fused into myotubes. Then the protein in myotubes was radiolabelled with L-[ 3,5-3H] tyrosine. The myotubes were cultured in DMEM medium containing 100 nmol/L insulin (n = 24, group B) , 100 nmol/L dexamethasone (n = 24, group C) , 100 nmol/L insulin and 100 nmol/L dexamethasone (n = 24, group D) , no insulin or dexamethasone (n =24, group A), respectively. Twenty-four hours after culture, the L-[3,5-3H] tyrosine content in culture medium and cells were determined, and the degradation rates of protein were calculated. The mRNA expressions of ubiquitin and protease C2 subunit were determined by Northern blot.

RESULTSThe degradation rates of myotube protein in group A(0. 38+/-0.04) was obviously lower than that in group C (0.50+/-0.03, P <0.01), but it was obviously higher than that in group B(0. 35+/-0.03, P <0.05). Though the degradation rates of myotube protein in group D (0.41+/-0. 03) was evidently lower than that in group C ( P < 0.01) , it was still higher than that in group A( P < 0.05 ). The mRNA expressions of ubiquitin and protease C2 subunit in group A ( the scale: 2. 4 kb ubiquitin was 0. 82+/-0. 15, 1. 2 kb ubiquitin was 0. 60+/-0. 10, C2 subunit was 0. 75+/-0. 16) was obviously lower than that in group C ( the scale: 2.4 kb ubiquitin was 2. 15+/-0. 23, 1.2 kb ubiquitin was 1.50+/-0. 14,C2 subunit was 1.50+/-0. 13 , P <0. 01) , but it in group D was lower than that in group C (the scale: 2. 4 kb ubiquitin was 1. 25+/-0. 17, 1. 2 kb ubiquitin was 0. 85+/-0. 09, C2 subunit was 0. 90+/-0. 15, P <0. 01) , and it was similar to that in group B (the scale: 2.4 kb ubiquitin was 0. 85+/-0.07, 1.2 kb ubiquitin was 0. 65+/- 0. 12, C2 subunit was 0. 76 +/-0. 09, P > 0. 05).

CONCLUSIONThe effects of insulin on the activity of ubiquitin-proteasome pathway and the proteolytic rate in normal myotubes were relatively weak. However, insulin can significantly inhibit the effects of dexamethasone on the gene expressions of ubiquitin system and the proteolytic rate in myotubes, but the mechanism needs further research.

Animals ; Cells, Cultured ; In Vitro Techniques ; Insulin ; pharmacology ; Male ; Muscle Fibers, Skeletal ; drug effects ; metabolism ; Muscle Proteins ; metabolism ; Rabbits ; Ubiquitin ; metabolism

OBJECTIVETo investigate the role of Src kinase inhibitor ZD6474 on the growth of multidrug-resistant K562/A02 cells and its regulatory mechanisms.

METHODSThe possible mechanisms of drug-resistance were tested by Western blot. Proliferation assays and cell cycle distribution were analyzed by WST metric analysis. Western blot were used to investigate the mechanisms of antiproliferative activity induced by tyrosine kinase inhibitor ZD6474. The in vivo anti-tumor activity was evaluated in K562, K562/A02 xenografted nude mice by administration of ZD6474 (25 - 100 mg×kg(-1)×d(-1), PO).

RESULTSCompared with parental K562 cells, marked high levels of p-Src and Src expression were detected in K562/A02 cells. WST results showed that the IC(50) values of ZD6474 on K562 and K562/A02 after 48 hours incubation were (1.61 ± 0.07) µmol/L and (3.22 ± 0.21)µmol/L, respectively. ZD6474 caused an accumulation of cells in the G(0)/G(1) fraction and apoptosis by inhibiting the expressions of p-Src and Src kinase. Administration of ZD6474 produced a dose-dependent inhibition of tumor growth. 50 mg/kg ZD6474 produced the growth inhibition rates of 43.7% and 56.3%, respectively in K562 and K562/A02.

CONCLUSIONOur results indicated that inhibiting Src kinase could induce K562/A02 cells apoptosis in vitro and in vivo.

Animals ; Apoptosis ; drug effects ; Cell Cycle ; drug effects ; Cell Proliferation ; drug effects ; Drug Resistance, Multiple ; drug effects ; Drug Resistance, Neoplasm ; drug effects ; Female ; Humans ; K562 Cells ; Mice ; Mice, Inbred BALB C ; Piperidines ; pharmacology ; Quinazolines ; pharmacology ; src-Family Kinases ; antagonists & inhibitors

OBJECTIVETo study the relationship between the infection of human papillomavirus (HPV) and external genital squamous cell carcinoma in situ.

METHODSHPV DNA was detected with the consensus primer by polymerase chain reaction (PCR) and its type was determined by restriction fragment length polymorphism (RFLP).

RESULTSHPV DNA was detected and HPV16 was the most frequently identified type in 29 (56.9%) of 51 cases of external genital squamous cell carcinoma in situ. HPV DNA was positive in 22 (55%) of 40 cases of bowenoid papulosis, among which 20 were of HPV16 type, one of HPV31 type, and one of HPV6 + 16 type. HPV DNA was positive in all 5 cases (100%) of Bowen's disease, among which 4 were HPV16 type and one of HPV6 + 16 type. HPV DNA was positive in 2 (33.3%) of 6 Queyrat erythroplasia cases and all were of HPV16 type.

CONCLUSIONHPV16 infection is strongly associated with the external genital squamous cell carcinoma in situ including bowenoid papulosis, Bowen's disease, and Queyrat erythroplasia.

Adult ; Aged ; Bowen's Disease ; virology ; Carcinoma in Situ ; virology ; Carcinoma, Squamous Cell ; virology ; DNA Probes, HPV ; DNA, Viral ; analysis ; Erythroplasia ; virology ; Female ; Genital Neoplasms, Female ; virology ; Genital Neoplasms, Male ; virology ; Humans ; Male ; Middle Aged ; Papillomaviridae ; isolation & purification ; Papillomavirus Infections ; virology ; Penile Neoplasms ; virology ; Polymorphism, Restriction Fragment Length ; Tumor Virus Infections ; virology ; Vulvar Neoplasms ; virology

Objective To study the HIV drug resistance (HIVDR) transmission in Kunming city of Yunnan province in 2010.Methods Referring to the guidelines for HIV drug resistance threshold survey (HIVDR-TS) set by WHO,62 plasma samples of recently reported HIV-infected individuals who were older than 25 years of age,were collected from January to August 2010.Genotyping of pol genetic mutations associated with HIVDR with reverse transcriptional PCR was performed and the prevalence of HIV-1 drug resistance transmission was evaluated.Results Of the 62 plasma samples,54 were successfully sequenced and genotyped on pol sequence.Based on the pol sequences,HIV subtypes including CRF08_BC ( 53.2％ ),CRF07_BC ( 25.5％ ),CRF01_AE ( 19.1％ )and C (2.1％) were identified.According to the time of sampling,the first 47 sequenced samples were used for drug resistance prevalence analysis.A protease inhibitor (PI) relative mutation was found in one sample.Based on the WHO standard,the prevalence of transmitted HIV-1 drug resistance was ＜5％.Conclusion HIV-1 drug resistant strains transmission was still catalogued as low prevalence level in Kunming.To prevent the increase of HIVDR prevalence,normative treatment and scientific management to AIDS patients seemed to be quite important.

Objective To understand the status of HIV sexual transmission among HIV- sero-discordant spouses and HIV-sero-accordant spouses in Yunnan province,to discuss the related factors and to provide evidence for HIV prevention and control strategy.Methods Five places with serious epidemic and 3 moderate ones were voluntarily,randomly selected.According to time sequence,300 spouses (600 people) with stable marriage were interviewed with questionnaire.Results HIV-sero-accordant spouses occupied for 40.7％ of the total spouses under survey,with the others were HIV-sero-discordant ones.Among the ones that had already been diagnosed in the families,sexual transmission was their main mode of transmission,which was accounted for 68.3％,followd by IDU as 19.7％.After disclosed the HIV test outcomes to their spouses,63.4％ HIV-sero-discordant spouses and 47.0％ HIV-sero-accordant ones changed their sexual behaviors.The rates of consistent condom use among the HIV-sero-discordant spouses increased from 16.8％ to 95.0％,and in HIV-sero-accordant spouses increased from 8.2％ to 60.9％.Data were analyzed by multi-factor logistic regression.Factors on influencing the sexual transmission in spouses would include condom use,frequency of sexual contacts and sexual transmission disease (STD) status etc.Conclusion The main transmission mode for the first HIV infected spouse was sexual transmission.Factors influencing sexual transmission in spouses would include condom use,frequency of sexual contacts,STD situation and husband was the first one being infected in the families,etc.Disclosure of the HIV results to the spouses could make a significant changes in the frequencies of sexual contact as well as the rate of condom use.

Objective To understand the knowledge,risk behaviors and HIV prevalence in men who have sex with men (MSM) in thirteen cities.Methods Target samples were chosen using the snowball-rolling method,with transverse KABP and HIV-antibody testing developed for those MSM in thirteen cities of Yunnan.Results A total of 1237 valid questionnaires and 1129 blood samples were collected.Basic knowledge on HIV and the rate of the response was 93.2％.81.1％ of the respondents had anal sex with male parmers in the last six months,of them 49.7％ could persistently using condoms in each anal sex episode.29.0％ of the respondents had sex with female partners in the last six months.The HIV prevalence among the studied MSM was 8.2％ and the prevalence of syphilis among them was 3.9％.Most risky factors of those MSM infected by HIV would include:not persistently use condom when having sex and co-infection of syphilis.Conclusion Both rates of HIV infection associated risk behaviors and HIV prevalence were high in MSM under study that called for more work on HIV prevention and control MSM in Yunnan.