Prognostic factors for chronic active Epstein-Barr virus infection

Chronic active Epstein-Barr virus infection (CAEBV) is a high-mortality and high-morbidity disease. To clarify the prognostic factors, a national survey was performed in Japan, and data for 82 patients who met the criteria for CAEBV were analyzed. Of these 82 patients, 47 were alive and 35 had already died. Multivariate analysis revealed that thromobocytopenia and age at disease onset were correlated with mortality. The probability of 5-year survival was 0.45 for older patients (onset age, > or = 8 years), 0.94 for younger patients (P<.001), 0.38 for patients with thrombocytopenia (platelet count < 12 x 10(4) platelets/microL at diagnosis), and 0.76 for patients without thrombocytopenia (P=.01). Furthermore, patients with T cell infection by EBV had shorter survival times than patients with natural killer cell infection (probability of 5-year survival, 0.59 vs. 0.87; P<.009). Patients with CAEBV with late onset of disease, thrombocytopenia, and T cell infection had significantly poorer outcomes.     

Epidemiologic and virologic characteristics of hepatitis B virus genotype B having the recombination with genotype C

BACKGROUND & AIMS: Hepatitis B virus (HBV) isolates of genotype B (HBV/B) with or without the recombination with genotype C over the precore region plus core gene have been reported. METHODS: All the 41 HBV/B isolates having the recombination with genotype C (HBV/Ba) possessed the nucleotide 1838 of A in contrast to that of G in all 29 of those without the recombination (HBV/Bj). Taking advantage of this single nucleotide polymorphism, a restriction fragment length polymorphism method was developed that distinguished HBV/Ba from HBV/Bj. RESULTS: HBV/Bj was detected in 90 of the 97 (93%) carriers of HBV/B from Japan, whereas HBV/Ba occurred in all 177 carriers of HBV/B from other countries (China, 20; Hong Kong, 45; Taiwan, 32; Thailand, 30; Vietnam, 30; and the United States, 20 [all of an Asian ethnicity]). In a case-control study, hepatitis B e antigen (HBeAg) and the double mutation in the core promoter (T1762/A1764) were significantly more frequent in 80 carriers each of HBV/Ba than HBV/Bj (35% vs. 18%, P < 0.05 and 33% vs. 15%, P < 0.05, respectively). Differences in the prevalence of HBeAg were more conspicuous between the carriers of HBV/Bj and HBV/Ba older than 30 years (5 of 66 or 8% vs. 16 of 62 or 26%, P < 0.01). CONCLUSIONS: HBV/B having the recombination with genotype C is frequent in Asia, except in Japan, and HBeAg is more prevalent in carriers of HBV/Ba than HBV/Bj.     

Detection and characterization of individual endocytosis of AMPA‐type glutamate receptor around postsynaptic membrane

Synaptic plasticity such as long‐term depression (LTD) has been regarded as a cellular mechanism of learning and memory. LTD is expressed by the decrease in number of postsynaptic AMPA‐type receptor (AMPAR) at glutamatergic synapses. Although endocytosis is known to play an essential role in the decrease in AMPAR on postsynaptic membrane, the difficulty to detect individual endocytic events hampered clarification of AMPAR dynamics around synapses. Previously, we developed a method to induce formation of postsynaptic‐like membrane (PSLM) on the glass surface and observed pHluorin‐tagged AMPAR around PSLM with total internal reflection fluorescence microscopy. By this method, individual exocytosis of AMPAR‐pHluorin was recorded in both PSLM and non‐PSLM. In other studies, endocytic vesicles containing pHluorin‐tagged receptors were visualized by changing extracellular pH. Here, we have combined PSLM formation method and rapid pH change method, and detected individual endocytic events of AMPAR around PSLM with high spatial and temporal resolutions. Endocytic events of AMPAR were characterized by comparison with those of transferrin receptor. Constitutive endocytosis of AMPAR was not dependent on clathrin and dynamin in contrast to that of transferrin receptor. However, AMPAR endocytosis triggered by LTD‐inducing stimulation was clathrin‐ and dynamin‐dependent.     

Utility of the new Japanese severity score and indications for special therapies in acute pancreatitis

Background  The Japanese severity score (JSS) for acute pancreatitis was revised in 2008. As special therapies for severe acute pancreatitis (SAP), continuous regional arterial infusion of protease inhibitor and antibiotics (CRAI) and enteral nutrition (EN) are now utilized in Japan. We investigated the usefulness of the new JSS and the indications for CRAI and EN based on the new JSS. Methods  We assessed the new JSS in 138 patients with SAP according to the previous Japanese criteria. Usefulness of the new JSS for the prediction of mortality rates was compared with conventional scoring systems by receiver-operator characteristic curve analysis. We analyzed the relationship between the new JSS and prognosis in patients with and without CRAI and EN, respectively. Results  Forty-five patients (33%) were assessed as having mild acute pancreatitis, and 93 patients (67%) were assessed as having SAP. Their mortality rates were 7 and 40%, respectively. The area under the curve for the prediction of mortality rates with the new JSS was 0.822 and was the highest among conventional scoring systems. In patients with new JSS ≥ 6, the mortality rate was lower in patients with CRAI than in patients without CRAI (P = 0.129). In patients with new JSS ≥ 4, the mortality rate was lower in patients with EN than in patients without EN (P = 0.016). Conclusions  The new JSS is useful and easier to use for the prediction of prognosis compared to the conventional scoring systems. EN was effective in reducing the mortality rate in patients with a new JSS ≥ 4.     

Apoptosis, cell proliferation and modulation of cyclin-dependent kinase inhibitor p21cip1 in vascular remodelling during vein arterialization in the rat

Neo-intima development and atherosclerosis limit long-term vein graft use for revascularization of ischaemic tissues. Using a rat model, which is technically less challenging than smaller rodents, we provide evidence that the temporal morphological, cellular, and key molecular events during vein arterialization resemble the human vein graft adaptation. Right jugular vein was surgically connected to carotid artery and observed up to 90 days. Morphometry demonstrated gradual thickening of the medial layer and important formation of neo-intima with deposition of smooth muscle cells (SMC) in the subendothelial layer from day 7 onwards. Transmission electron microscopy showed that SMCs switch from the contractile to synthetic phenotype on day 3 and new elastic lamellae formation occurs from day 7 onwards. Apoptosis markedly increased on day 1, while α-actin immunostaining for SMC almost disappeared by day 3. On day 7, cell proliferation reached the highest level and cellular density gradually increased until day 90. The relative magnitude of cellular changes was higher in the intima vs . the media layer (100 vs . 2 times respectively). Cyclin-dependent kinase inhibitors (CDKIs) p27^Kip1 and p16^INKA remained unchanged, whereas p21^Cip1 was gradually downregulated, reaching the lowest levels by day 7 until day 90. Taken together, these data indicate for the first time that p21^Cip1 is the main CDKI protein modulated during the arterialization process the rat model of vein arterialization that may be useful to identify and validate new targets and interventions to improve the long-term patency of vein grafts.     

PIVKA-II (protein induced by vitamin K absence-II) status in newborns exposed to anticonvulsant drugs in utero

Using PIVKA-II and Hepaplastin test, 5 neonates exposed to anticonvulsant drugs in utero were assessed 5 days after birth. None showed any sign of clinical bleeding, but all had PIVKA-II values over 1 microgram/ml. In controls, only 96 of 1,166 (8.2%) neonates had PIVKA-II values over 1 microgram/ml. The difference in the incidence rate was significant (p less than 0.005). Three of 5 epileptic mothers received valproatic acid and/or diazepam but no barbiturates and/or hydantoin.     

Polo-like kinase expression in normal human endometrium during the menstrual cycle

The enzyme, polo-like kinase (PLK), is a mammalian serine/threonine kinase involved in cell cycle regulation. A great deal of evidence regarding the role of PLK in the cell cycle has been obtained through studies of cultured cells, though little is known about its function or even expression in vivo. The endometrium undergoes rapid proliferation and differentiation under ovarian steroid hormone control during the 28-day cycle. Thus, normal endometrium provides an excellent model in which to study the hormone dependency of PLK expression. In the present study, we examined the features of PLK expression in 20 samples of normal human endometrium during the menstrual cycle. The expression of Ki-67 and proliferating cell nuclear antigen (PCNA) were also examined as markers of proliferation. Immunohistochemical studies showed that PLK staining was detected in the basement membrane of many endometrial glands, stromal cells, and some endothelial cells. The number of PLK-positive endometrial gland cells was significantly higher in the late proliferative phase (19.16% +/- 4.98%) and the early secretory phase (19.28% +/- 4.99%) than in the early proliferative phase (2.60% +/- 2.33%) or the late secretory phase (5.76% +/- 2.16%) (P<0.0001). PLK expression seemed to be correlated with the expression of Ki-67 and PCNA in many endometrial glands and stromal cells particularly in the late proliferative phase, reflecting a role of PLK in cellular proliferation. Nevertheless, in the early secretory phase, at which point the expression of Ki-67 and PCNA decreased in endometrial glands, PLK was strongly expressed. This finding suggests that PLK may have some post-mitotic functions in certain specialized cell types. Although the highest expression of PLK was observed in the late proliferative and the early secretory phases, the expression drastically decreased in the late secretory phase. These findings, taken together, indicate that the expression of PLK in normal endometrium fluctuates over the course of the menstrual cycle, suggesting in turn that PLK is associated with hormone-dependent cellular proliferation and that hormone functions may be involved in its regulation.     

Case report of dysgerminoma in a patient with 46,XX pure gonadal dysgenesis

A clinicopathological study of a 42-year-old female with pure gonadal dysgenesis and dysgerminoma was made. At the age of 29, the patient with primary amenorrhea had been evaluated clinically and cytogenetically. (1) The results of cytogenetic studies were X-chromatin positive and revealed a karyotype in peripheral blood leukocytes of 46,XX. (2) Laboratory studies indicated hypergonadotropic hypogonadism and no response of the gonads to the human menopausal gonadotropin stumulation test. (3) At laparotomy, the gonads were streak-like. Pathological examinations of biopsy specimens from both gonads revealed dense, fibrous connective tissue resembling ovarian stroma and no primary follicles. Eleven years after the laparotomy, the patient complained of lower abdominal distention and severe pain, and laparotomy then revealed a 15 × 17-cm right solid adnexal mass occupying the pelvic cavity. The histological diagnosis of tissues from the partially removed tumor was pure dysgerminoma. Second-look operation after Linac X-ray irradiation showed complete remission of the residual tumor. Insofar as we are aware, the present patient represents the first case of dysgerminoma which occurred in the dysgenetic gonads of a phenotypic female with normal 46,XX sex-chromosomal constitutions in peripheral blood leukocytes and the skin fibroblasts although a possibility exists that mosaicism was possibly present but undetected, particularly since the streak gonads were not analyzed chromosomally.