A new variant of the ATP13A2 gene in Chinese patients with early-onset parkinsonism

Parkinson＇s disease （PD） is the second most common neurodegenerative disorder characterized by a selective loss of nigrostriatal dopaminergic neurons. Clinical manifestations of this complex disease include resting tremor, bradykinesia, postural instability, gait difficulty and rigidity. Approximately 5%-10% of patients have genetic factors, yet etiology of PD remains unclear. Genetic deficits, environmental exposure, oxidative stress, mitochondrial dysfunction,     

HIV-1包膜蛋白2G12和2F5中和表位的改造对假病毒形成及中和活性的影响

目的 研究HIV-1膜蛋白(Env)特定中和表位的改造对功能性假病毒形成及中和活性的影响.方法 采用环形诱变及Dpn I筛选的方法对Env进行定点突变,将2G12和2F5两个中和表位整合入不含该表位的BC亚型的Env上,比较改造对假病毒的形成情况及对2G12和2F5单抗的中和活性的影响.结果 对5株假病毒(BC02、BE03、BC04、BC05和BC12)的Env特定中和表位进行改造,其中BC04和BCl2的2G12表位改造后,不能形成假病毒,BC02、BC03和BC05增加2G12和2F5两个表位后,仍能够形成假病毒,且假病毒滴度较改造前无明显变化,改造后的BC03假病毒较改造前对单抗2G12和2175的中和活性均有所提高,而改造后的BE02和BC05假病毒较改造前对单抗2F5的中和活性增强,而对单抗2G12的中和活性无变化.结论 2G12中和表位部分位点的改造影响假病毒的形成,中和表位的增加能够提高单抗2G12的中和活性,为免疫原的优化提供了新思路.     

Occurrence and Characteristics of Class 1 and 2 Integrons in Pseudomonas aeruginosa Isolates from Patients in Southern China

Class 1 and 2 integrons were detected in 45.8% (54/118) and 19.5% (23/118) of our tested Pseudomonas aeruginosa isolates, respectively. Three strains were positive for both the integrons. This is the first report of class 2 integrons in P. aeruginosa and also of isolates carrying class 1 and 2 integrons simultaneously.Pseudomonas aeruginosa remains one of the most important pathogens in the nosocomial setting (14), and it not only is naturally resistant to many antimicrobial agents but also has the distinctive capacity via multiple mechanisms to become resistant to virtually all the antibiotics available commercially (9, 38). A genetic element, the integron, is potentially a major agent in the dissemination of multidrug resistance among gram-negative bacteria, especially in Pseudomonas (16). Gene cassettes, present in the variable region of integrons, are discrete mobile units comprising a gene, usually an antibiotic resistance gene, and a recombination site that is recognized by an integrase. The class 1 integron has been identified as a primary source of resistance genes within gram-negative and -positive bacteria (6, 20, 33, 36, 40, 41, 42), and the class 2 integron has been seen in Acinetobacter sp. isolates throughout the world (28). However, class 2 integrons in P. aeruginosa strains had not yet been investigated. In this study, 118 imipenem-resistant P. aeruginosa isolates were chosen for the investigation of class 1 and 2 integrons because of the relatively high integron-positive rate in imipenem-resistant isolates.From 2001 to 2005, a total of 118 consecutive nonduplicated P. aeruginosa isolates which were intermediate or resistant (nonsusceptible) to imipenem (IMP; MIC > 8 μg/ml) were isolated from the First Affiliated Hospital of Jinan University, an 850-bed tertiary-level teaching hospital in Guangzhou, China. Identification of isolates to the species level and antimicrobial susceptibility testing were performed with the Vitek system (bioMerieux Vitek Systems Inc., Hazelwood, MO). The quality control strain used was P. aeruginosa ATCC 27853. Template DNA used for PCR was prepared as described previously (16). Detection and characterization of class 1 and 2 integrons were performed as described previously (35, 41). PCR products of the variable region were further characterized by restriction fragment length polymorphism (RFLP), and at least two different restriction endonucleases were chosen for each RFLP assay, and the DNA sequence for at least one of the variable region amplification products belonging to each of the individual RFLP patterns was determined as described previously (35). Seventy-four integron-positive P. aeruginosa isolates were subjected to genotyping analysis by randomly amplified polymorphic DNA PCR (RAPD-PCR) as described previously (35).The multidrug resistance (defined as resistance to six or more antibiotics) rates of integron-positive and -negative strains were 93.2% and 18.2%, respectively (Table ​(Table1).1). Class 1 integron was detected in 54 isolates, and 51 strains carried the 3′ conserved region of qacEΔ1-sul1. Seven different sizes of variable region were found, with fragments with lengths ranging between 879 bp and 2,655 bp (Table ​(Table2).2). The array of the aacA4-catB3-dfrA1 noncoding gene cassette has been reported previously (16). The defective class 1 integron with a sul3 gene, which was identical with that seen in Salmonella enterica serovar Typhimurium ({"type":"entrez-nucleotide","attrs":{"text":"AY047357","term_id":"15983740","term_text":"AY047357"}}AY047357), had never been reported to be seen in isolates of P. aeruginosa. Class 2 integrons were found in 23 P. aeruginosa isolates, and all strains harbored the same array of three cassettes, dfrA1-sat1-aadA1, which was identical to that found in Tn7. Three strains had both class 1 and 2 integrase genes. No class 3 integrase gene was detected in any of the isolates examined. RAPD-PCR analysis divided 74 integron-positive P. aeruginosa strains into eight different groups with different RAPD patterns (genotypes A to H) (Fig. ​(Fig.1).1). Fifty-one class 1 integron-positive strains and 3 class 1 and 2 integron-positive strains were of types A, B, C, F, G, and H, and 20 class 2 integron-positive strains were of types D and E (Table ​(Table22).Open in a separate windowFIG. 1.RAPD-PCR patterns of 74 integron-positive Pseudomonas aeruginosa isolates.

TABLE 1.

Association between antibiotic susceptibility profile and integrons in 118 Pseudomonas aeruginosa isolates

借鉴军队院校管理模式 推行量化考评规范实习生管理

本文通过对当前军队医院实习生管理现状的分析,探讨了军队院校管理模式、量化考评在医院实习生管理中的作用,提出了一些具体的工作方法和措施。     

Stage T1 glottic carcinoma: results of radiation therapy or laser excision

A retrospective analysis was made of the data on 60 patients with stage T1 glottic carcinoma (43 T1a, 17 T1b) who received radiation therapy and 17 patients with T1a disease who underwent laser excision as the primary treatment modality. Patients who received radiation therapy achieved 3- and 5-year actuarial local control rates of 92% and 89% for T1a and 77% and 77% for T1b disease, respectively. In patients who underwent laser excision (all with T1a disease), the 3-year local control rate was 77%. Of the 42 evaluable irradiated T1a patients, 31 (74%) had a normal to near-normal voice, eight (19%) had mild or intermittent hoarseness, and three (7%) had persistent hoarseness. Of the 13 evaluable patients in the laser-excision group, four (31%) had a normal to near-normal voice, five (38%) had mild or intermittent hoarseness, and four (31%) had persistent hoarseness. The difference in the quality of voice between these two groups is statistically significant (P = .012), although the ultimate local control rate after salvage therapy for irradiated patients (97%) was similar to that for laser-excision patients (94%).     

Visual identification of bacterially contaminated red cells

There have been increasing numbers of reports of transfusion-acquired Yersinia enterocolitica bacteremia (including several fatal cases). Fifteen units of whole blood were inoculated with various concentrations of Y. enterocolitica serotype 0:3 and processed into AS-3 preserved red cells (RBCs). Consistent growth of the organism was found at inoculum concentrations greater than or equal to 10 colony-forming units per mL. In all 13 units of RBCs that supported the growth of Y. enterocolitica, a darkening in color (due to hemolysis and a decrease in pO2) was observed in the bag. The attached sample segments, which were sealed from the main unit, remained sterile and did not darken. This color change was apparent in all the contaminated units by Day 35, which was 1.5 to 2 weeks after the bacteria were first detected in cultures of the blood. Hence, by comparison of the color of the segment tubing with that of the unit itself, units grossly contaminated with Y. enterocolitica can be identified prior to transfusion. Moreover, review of photographs on file at the Centers for Disease Control revealed this dramatic color change in 2 units of blood that caused transfusion-transmitted sepsis (Enterobacter agglomerans and an unidentified gram-negative bacillus, not Yersinia sp.), which demonstrated that the color change was not limited to Y. enterocolitica. This method of visual identification of contaminated units of blood could decrease the incidence of posttransfusion bacterial sepsis.     

Ultrasound of the posterior circumflex humeral artery

Quadrilateral space syndrome (QSS) is described as compression neuropathy of the axillary neurovascular bundle in the quadrilateral space of the shoulder. This neurovascular bundle includes the posterior circumflex humeral artery (PCHA). Historically, angiography and more recently magnetic resonance angiography have been used to assess occlusion and stenosis of the PCHA in cases of suspected QSS. These traditional imaging techniques have a number of disadvantages in terms of cost, availability, invasiveness and patient comfort. We undertook to examine the ability of ultrasound to reliably visualise the PCHA. Asymptomatic adult volunteers were recruited from staff, and patients attending the radiology department who presented for pathologies unrelated to the shoulder. We used a new technique to assess blood flow in the PCHA, performing the scan from a posterolateral approach on the upper arm just above the level of the surgical neck of the humerus. This technique enabled the scan to be undertaken with the patient seated comfortably. Fifty volunteers were recruited into the study. The mean (±SD) age was 35 (±14 years). The PCHA was visualised in all patients. Our method was able to maximise Doppler sensitivity and visualisation of the artery without discomfort to the patient in less than 10 min. Ultrasound can be used to reliably visualise the PCHA. Ultrasound has potential to be used in the assessment of the PCHA in cases of QSS.     

Clinical and economic impact of enterovirus illness in private pediatric practice

OBJECTIVE: To characterize the acute clinical course and economic burden of nonpolio enteroviral (NPEV) illness in the summer/fall season as seen in private pediatric practice. METHODS: We prospectively studied 380 children aged 4 to 18 years with systemic NPEV syndromes presenting to private suburban pediatric practices. Seventy-three asymptomatic controls were concurrently enrolled. Clinical diagnosis of NPEV illness was based on the presence of fever plus at least one of the following: headache and stiff neck (n = 2); myalgia and malaise (n = 105); nonpuritic maculopapular rash (n = 10); papulovesicular stomatitis (n = 214); papular rash of the hands, feet, and mouth (H/F/M) (n = 30); or pleurodynia (n = 11). Study participants were enrolled during a 4-month time span (July-October, 1994) and followed daily for 14 days. A parent symptom diary card and twice weekly phone contacts by study nurses characterized the illness to include the frequency of health care contacts, the necessity for laboratory tests, medication use, and school/work absenteeism. RESULTS: Three hundred seventy-two (98%) children completed the study; 122 (33%) of the patients were confirmed to be infected with NPEV. Confirmed NPEV infection was more frequently observed in Rochester, NY (85/147 = 58%) than in Scottsdale, AZ (32/224 = 14%). The age group 4 to 12 years comprised 79% to 90% of the enrollees, depending on the syndrome. Median duration of illness and median number of missed days of school/summer camp/work for the enrolled patients was: meningitis (7 days ill, 2 days missed), myalgia/malaise (9 days ill, 3 days missed), rash (6 days ill, 4 days missed), stomatitis (7 days ill, 2 days missed), H/F/M (7 days ill, 1 day missed), and pleurodynia (8 days ill, 3 days missed). Direct medical costs varied from $69 per case to $771 per case and indirect costs, attributable primarily to parent missed work and/or sick-child care, varied from $63 per case to $422 per case for H/F/M and meningitis, respectively. In households, H/F/M spread to 50% of siblings and 25% of parents. CONCLUSIONS: In our study population, NPEV infection: 1) caused sufficient illness to prompt physician visits in summer and fall; 2) occurred more frequently in 4 to 12 year olds than in adolescents; 3) produced various clinical syndromes concurrently during the same months in the same season of a given year; 4) varied in occurrence geographically; 5) was characterized by numerous symptoms of longer duration than previously recognized; and 6) produced a significant economic impact by generating both direct and indirect costs.