Transmission of chromosomally integrated human herpesvirsus 6 (HHV‐6) variant A from a parent to children leading to misdiagnosis of active HHV‐6 infection

Abstract: Only a handful of cases of chromosomally integrated human herpesvirus 6 (CI‐HHV‐6) have been reported, suggesting that this phenomenon is rare. We here present a familial case of HHV‐6 variant A (HHV‐6A) transmission through a generation, which was identified in the setting of allogeneic hematopoietic stem cell transplantation (HSCT). A 31‐year‐old man with myelodysplastic syndrome underwent allogeneic HSCT from a human leukocyte antigen‐identical sibling, and was found to be continuously yielding high copy numbers of HHV‐6A DNA in plasma evaluated by real‐time polymerase chain reaction (PCR). Antiviral therapy with ganciclovir or foscarnet failed to decrease the copy numbers. HHV‐6A DNA was detected in the patient's buccal mucosa and hair follicles, and was also detected in the plasma, whole blood, and buccal mucosa of the patient's father and 2 siblings, but not in his mother. The sequences of HHV‐6A DNA isolated from all family members were identical. Since monitoring of HHV‐6 by PCR has been widely introduced to the field of HSCT, transplant physicians should be aware of such an alternative form of HHV‐6 transmission, particularly when HHV‐6A is detected.     

抗乙肝病毒感染的核苷类药物研究现状

搜集近年的文献资料,按照不同的药物结构和作用机制综述抗HBV感染的核苷类药物的研究进展。目前,设计开发各类核苷类药物已成为治疗乙肝病毒感染的热点。     

Effects of Nutrition Education Program for the Japan Diet on Serum LDL-Cholesterol Concentration in Patients with Dyslipidemia: A Randomized Controlled Trial

Aim: The Japan Diet (JD) recommended by the Japan Atherosclerosis Society based on the traditional Japanese diet is presumably favorable for preventing atherosclerotic cardiovascular diseases, but few high-quality controlled clinical trials have examined its benefits as compared with other diets. We studied effects of nutrition education for JD intake as compared with partial JD (PJD) intake on serum lipids and inflammatory parameters in subjects with dyslipidemia. Methods: A randomized parallel controlled clinical trial was conducted on outpatients with dyslipidemia. Participants were randomly divided into the JD or the PJD group. Face-to-face nutrition education based on each diet at baseline and at 3 months, as well as monthly counseling by mail during the intervening 3-month period, were provided and participants practiced up to 6 months. Both groups were advised to reduce consumptions of animal fat/ fatty meat/poultry, confections, and alcoholic drinks. Additionally, the JD group participants were recommended to consume more fish, soybean products especially natto, vegetables, and seaweed/mushrooms/konjak, and to switch from refined to unrefined cereals or barley. Results: Mean LDL-cholesterol was 125 +/- 29 mg/dL at baseline, and the JD group ( n =49) showed a greater mean LDL-cholesterol decrease than the PJD group ( n =49) [- 8 mg/dL in JD vs 1 mg/dL in PJD, difference, -9 mg/dL (95%CI, -17 to 0) p =0.043)], and triglyceride ( p =0.023) and insulin ( p =0.033) reductions were larger in the JD group than in the PJD group at 6 months. Conclusion: Nutrition education for JD intake was suggested to improve serum lipid and metabolic parameters in patients with dyslipidemia.     

微电极阵列技术在大鼠心脏组织电生理特性研究的应用

目的应用微电极阵列(MEAs)标测技术研究大鼠心脏组织场电位(FPs)特性,比较心房和心室组织片场电位特性及电激动的传导.方法制备SD大鼠心脏组织片标本(大小5 mm×5 mm,厚度约2 mm);采用同步60个位点MEAs标测技术,用5 μV×1 ms的刺激脉冲连续刺激,刺激间隔为1s,引出并记录组织场电位.比较心房和心室组织片场电位形态和FPs传导时间.结果心室肌组织片最大场电位(FPmax)和最小场电位(FPmin)与心房肌FPmax、FPmin相比,差别均无统计学意义(P＞0.05);而心室组织片场电位时程(FPdur)明显长于心房组织FPdur (P＜0.01);心房组织片FPs传导时间(66.46±6.73 ms)长于心室组织FPs传导时间 (47.40±5.62 ms) (P＜0.01).结论MEAs标测技术能记录和分析相对微观领域心脏组织片的场电位、电激动传导时间和电激动传导顺序等信息,是一种进行传导异常性心律失常机制研究和相关药物干预研究的可靠工具.     

Effects of ticlopidine on the neurologic outcome and the hemorheologic pattern in the postacute phase of ischemic stroke: a pilot study

This double-blind pilot study observed the effects of a twenty-one day oral ticlopidine treatment (250 mg/twice daily) on the neurologic outcome and the hemorheologic pattern of 15 patients and 15 placebo-treated controls. Patients and controls (age range sixty-six to eighty-six years) were included in the study within twelve hours of the onset of ischemic stroke, confirmed clinically and by computerized tomography. Scores on Hachinski's Scale and the following hemorheologic parameters were monitored weekly for twenty-one days: fibrinogen levels, the whole blood, unfractionated white and red blood cell filterability rates (through 5-micron-pore-diameter filters using a constant-flow positive-pressure system), and the leukocyte count and activation (by microscopic observation). The results showed treatment with ticlopidine improved the neurologic outcome (Hachinski's Score +36%, p less than 0.03) slightly but significantly (p less than 0.001) increased the average values of the whole blood (+19%) and red cell (+17%) filterability rates and decreased fibrinogen levels (-17%).     

Allogeneic hematopoietic stem cell transplantation with fludarabine, melphalan, and total body irradiation as a conditioning for elderly patients with myeloid malignancies

A variety of reduced-intensity conditionings have been used in the reported studies of allogeneic hematopoietic stem cell transplantation (HSCT) for elderly patients with myeloid hematological malignancies. This study retrospectively analyzed the outcome of allogeneic HSCT for 10 patients aged 50 years or older with myeloid hematological malignancies after conditioning with fludarabine (125 mg/m(2)), melphalan (140 mg/m(2)) and total body irradiation (TBI; 8 Gy). Median age of the patients was 56.5 years, and diagnoses included acute myelogenous leukemia, advance myelodysplastic syndrome, and secondary myelofibrosis. Sources of stem cells were bone marrow from sibling (n=4) or unrelated donor (n=6). Both overall and disease-free survival rates were 40.0% (95% CI: 10.6~69.4%). Causes of death were relapse (n=2), fungal infection (n=2), and secondary malignancies (n=2). Because of a high incidence of transplant-related mortality, further refinement of this conditioning is required.     

Caenorhabditis elegans RSD-2 and RSD-6 promote germ cell immortality by maintaining small interfering RNA populations

Germ cells are maintained in a pristine non-aging state as they proliferate over generations. Here, we show that a novel function of the Caenorhabditis elegans RNA interference proteins RNAi spreading defective (RSD)-2 and RSD-6 is to promote germ cell immortality at high temperature. rsd mutants cultured at high temperatures became progressively sterile and displayed loss of small interfering RNAs (siRNAs) that target spermatogenesis genes, simple repeats, and transposons. Desilencing of spermatogenesis genes occurred in late-generation rsd mutants, although defective spermatogenesis was insufficient to explain the majority of sterility. Increased expression of repetitive loci occurred in both germ and somatic cells of late-generation rsd mutant adults, suggesting that desilencing of many heterochromatic segments of the genome contributes to sterility. Nuclear RNAi defective (NRDE)-2 promotes nuclear silencing in response to exogenous double-stranded RNA, and our data imply that RSD-2, RSD-6, and NRDE-2 function in a common transgenerational nuclear silencing pathway that responds to endogenous siRNAs. We propose that RSD-2 and RSD-6 promote germ cell immortality at stressful temperatures by maintaining transgenerational epigenetic inheritance of endogenous siRNA populations that promote genome silencing.Cellular lifespan is regulated by developmental fate. Somatic cells typically have a limited lifespan of a single generation. In vertebrates, proliferation of somatic cells is governed by an irreversible state of cell cycle arrest that can occur in response to cellular stresses, termed senescence. Senescence is a powerful tumor suppressor mechanism, but it may also contribute to aging. Endogenous stresses have been clearly shown to accumulate with age to cause p53-dependent senescence include telomere attrition and irreparable telomere-associated DNA damage (1, 2). Although distinct sources of endogenous stress accumulate as somatic cells proliferate and induce p16-mediated senescence, natural triggers of this pathway remain unclear (2).One approach to address forms of stress that could contribute to proliferative aging of somatic cells is to study germ cell immortality. Germ cells have an effectively unlimited proliferative capacity as they are transmitted through the generations (3). Germ cell immortality can be studied by using Caenorhabditis elegans mortal germline (mrt) mutants that initially possess normal levels of fertility but become progressively sterile. Consistent with telomere attrition as a cause of proliferative aging in humans (4), mrt mutants with highly penetrant progressive sterility phenotypes can suffer from progressive telomere shortening as a consequence of defects in telomerase-mediated telomere replication (5, 6), and these mutants typically become sterile at any temperature that they are propagated (7).We report that the RNAi spreading proteins RNAi spreading defective (RSD)-2 and RSD-6 (8) are required for germ cell immortality at elevated temperatures. RSD-6 is a Tudor domain protein that is homologous to TDRD5 of mammals, which plays a role in spermatogenesis and suppression of transposons (9), whereas RSD-2 does not have any clear mammalian homologs (8). We found that the transgenerational fertility defects of rsd-2 and rsd-6 mutants are not restricted to spermatogenesis and are accompanied by desilencing of transposons and other repetitive loci, although transposition does not appear to be the trigger of sterility.