Evaluation of the genetic stability of the temperature-sensitive PB2 gene mutation of the influenza A/Ann Arbor/6/60 cold-adapted vaccine virus

A single-gene reassortant bearing the PB2 gene of the A/Ann Arbor/6/60 cold-adapted virus in the background of the A/Korea/82 (H3N2) wild-type virus is a temperature-sensitive (ts) virus with an in vitro shutoff temperature of 38 degrees C. A single mutation at amino acid (aa) at 265 (Asp-Ser) of the PB2 protein is responsible for the ts phenotype. This ts single-gene PB2 reassortant virus was serially passaged at elevated temperatures in Madin-Darby canine kidney cells to generate ts+ phenotypic revertant viruses. Four ts+ phenotypically revertant viruses were derived independently, and each possessed a shutoff temperature for replication in vitro of > 40 degrees C. Each of the four phenotypically revertant viruses replicated efficiently in the upper and lower respiratory tracts of mice and hamsters, unlike the PB2 single-gene reassortant virus, confirming that the ts phenotype was responsible for the attenuation of this virus in rodents. Mating the ts+ revertants with wild-type virus yielded ts progeny in high frequency, indicating that the loss of ts phenotype was due to a suppressor mutation which was mapped to the PA gene in each of the four independently derived ts phenotypic revertants. Nucleotide sequence analysis confirmed the absence of new mutations on the PB2 gene and the presence of predicted amino acid changes in the PA proteins of the revertant viruses. These studies suggest that single amino acid changes at aa 245 (Glu-Lys) or 347 (Asp-Asn) of the PA protein can completely suppress the ts and attenuation phenotypes specified by the Asp-Ser mutation at aa 265 of the PB2 protein of the A/Ann Arbor/6/60 cold-adapted virus.     

Strategy for the retreatment of failed Helicobacter pylori eradication therapy: a case series

BACKGROUND: Helicobacter pylori eradication therapy can be unsuccessful in 5 to 20% of patients. AIM: To investigate the validity of a strategy using triple therapies for the retreatment of patients with eradication failure, avoiding retreatment with antibiotics prone to induce resistance after use in the first treatment. PATIENTS AND METHODS: From a consecutive sampling of 108 patients still Helicobacter pylori-positive after a first course of antibiotic-based treatment, 74 (68.5%) agreed to a second course of triple therapy. Group 1 (N = 17): treatment failures on an imidazole (1)-based therapy were retreated with clarithromycin (C)-based regimen; Group 2 (N = 28): failures on a C-based therapy with an I-based regimen; Group 3 (N = 7): failures on an IC-based therapy using an I-based regimen and Group 4 (N = 22): failures on a non-I/non-C based therapy with either an I-based, C-based or IC-based regimen. The presence of Helicobacter pylori was assessed by histology and the CLO-test at study entry and two months after stopping therapy. RESULTS: Nine patients were withdrawn from the study (12.2%) due to a lack of end point endoscopy. Helicobacter pylori was cured after the second course of therapy in all but seven patients [10.7% failure by Per Protocol analysis, 21.6% by Intention-To-Treat analysis]. No statistically significant differences were found between the four groups (Group 1: 92.9% PP, 76.5% ITT; Group 2: 90.9% PP, 71.4% ITT; Group 3: PP and ITT 85.7%; Group 4: PP and ITT 86.4%). Minor adverse events were experienced in nine, none of whom required withdrawal from the drug therapy. CONCLUSIONS: A second course of triple therapy with alternate antibiotics effectively eradicated Helicobacter pylori, with only very few treatment failures. This suggests that the therapeutic strategy employed may be recommended.     

新的大功率音频开关家族在合弦音乐振铃智能电话中实现高保真立体声信号开关功能

亚微米技术运用标准传输门单元 (经常出现在电子方法文献中)方法,为先进的具有悦耳铃声的新型移动电话平台提供了适合的功率控制性能。新型移动电话等电池供电设备的微控制器必须始终保持较低的功耗,必须始终需要较低的电源电压;其它半导体设备,如功率放大器和彩屏控制器,即使电源电压更高,也必须具有适当的与微控制器相一致的控制水平。     

The cooccurrence of DSM-III-R personality disorders

The distinction between personality disorder diagnoses is often unclear because of the frequent cooccurrence of one or more of the diagnoses. To date, studies using sample sizes large enough to evaluate the rates of cooccurrence in the less prevalent personality disorders have not been conducted. The Structured Interview for Diagnosis of Personality-Revised, a semistructured instrument designed to yield reliable personality disorder diagnoses, was used to evaluate 1116 subjects for the presence of DSM-III-R personality disorder diagnoses. Cooccurrence rates and odds ratios were calculated for each pair of diagnoses. There was a high degree of cooccurrence between the cluster A personality disorders, between the cluster C personality disorders, and between narcissistic, borderline, and histrionic disorders. In addition, there was also a high frequency of avoidant personality disorders within the cluster A personality disorder diagnoses. Possible explanations for the high degree of cooccurrence and the potential implications for the DSM-IV personality disorder diagnoses are discussed.     

Immunocytochemical investigation on dysplastic human tissue from epileptic patients

In this report we describe three patients with developmental cortical abnormalities (generally referred as cortical dysplasia), revealed by MRI and operated on for intractable epilepsy. Tissue, removed for strictly therapeutic reasons, was defined as the epileptogenic area by electroclinical data and stereo EEG (SEEG) recordings. Tissue samples were processed initially for histology, and selected sections were further processed for immunocytochemical investigation in order to determine whether the region of cortical dysplasia was co-extensive with the epileptogenic area. In two patients with nodular heterotopia, disorganized aggregates of neurons (as revealed by neuronal cytoskeletal markers) were found within the nodules. Both pyramidal and local circuit neurons were present in the nodules, but no reactive gliosis was present. When nodules reached the cortex, the cortical layers were disrupted. In the patient with localized cortical dysplasia, a complete disorganization of the cortical lamination was found, and numerous neurons were also present in the white matter. Disoriented pyramidal neurons weakly labelled with cytoskeletal neuronal markers were also present but no cytomegalic cells were found. One of the patients with nodular heterotopia underwent only partial resection of both the 'epileptogenic area' and of the lesion; this patient still presents with seizures. The other patient with nodular heterotopia is seizure-free after a complete lesionectomy and excision of the epileptogenic area. The third patient, with focal cortical dysplasia, had two surgeries; she became seizure-free only after the excision of the epileptogenic area detected by SEEG recording. The present data suggest that the dysplastic areas identified by MRI should not be considered as the only place of origin of the ictal discharges. From the neuropathological point of view, the focal cortical dysplasia can be considered as a pure form of migrational disorder. However, the presence of large aggregates of neurons interspersed within the white matter, in the subcortical nodular heterotopia, suggests that a defect of neuronal migration could be associated with an exuberant production of neuroblasts and/or a disruption of mechanisms for naturally occurring cell death.     

Therapeutic approach in arterial hypertension with renal artery stenosis

Screening for renal artery stenoses in hypertensive patients aims at detecting lesions whose treatment (renal revascularization) will normalize or reduce blood pressure and correct or prevent reduced glomerular filtration. Consequently, screening tests such as renal artery duplex Doppler scanning, renal scintigraphy or digital-subtraction angiography are used in patients in whom hypertension is severe, drug-resistant or associated with renal failure. Surgical repair or transluminal angioplasty is not warranted for all stenoses, however, particularly in atheromatous stenoses where these procedures have a 1% mortality, a 10% morbidity and a 30% failure rate to improve blood pressure despite adequate anatomical outcome. Predictors of favourable blood pressure outcome following revascularization are aetiological (fibrous dysplasia rather than atheroma), historical (young age, short duration of hypertension), physiological (renal ischaemia confirmed by scintigraphy, lateralizing renal vein renin ratio) and anatomical (truncal rather than ostial or branch stenoses). Outcome of surgery and transluminal angioplasty has only been documented in retrospective, uncontrolled reports in which blood pressure improvement is overestimated via the placebo effect, habituation to blood pressure readings and optimization of drug treatment, the latter being frequently required despite adequate revascularization. The first prospective randomized trials evaluating angioplasty in atheromatous stenoses are underway and should provide objective information concerning the risk/benefit ratio of this procedure.