Outcomes After Aortic Valve Replacement for Asymptomatic Severe Aortic Regurgitation and Normal Ejection Fraction

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Japanese Versus Non-Japanese Patients with Transient Ischemic Attack or Minor Stroke: Subanalysis of TIA registry.org

BackgroundTIAregistry.org is an international cohort of patients with transient ischemic attack (TIA) or minor stroke within 7 days before enrollment in the registry. Main analyses of 1-year follow-up data have been reported.⁵ We conducted subanalysis on the baseline and 1-year follow-up data of Japanese patients.MethodsThe patients were classified into 2 groups based on Japanese ethnicity, Japanese (345) and non-Japanese (3238), and their baseline data and 1-year event rates were compared. We also determined risk factors and predictors of 1-year stroke.ResultsCurrent smoking, regular alcohol drinking, intracranial arterial stenosis, and small vessel occlusion; and hypertension, dyslipidemia, coronary artery disease, and extracranial arterial stenosis were more and less common among Japanese patients, respectively. Stroke risk was higher and TIA risk was lower at 1-year follow-up among Japanese patients. The baseline risk factors for recurrent stroke were diabetes, alcohol drinking, and large artery atherosclerosis. Independent predictors of 1-year stroke risk were prior congestive heart failure and alcohol consumption.ConclusionsThe two populations of patients featured differences in risk factors, stroke subtypes, and outcome events. Predictors of recurrent stroke among Japanese patients included congestive heart failure and regular alcohol drinking. Strategies to attenuate residual risk of stroke aside from adherence to current guidelines should take our Japanese-patient specific findings into account.     

Golgi study on brain of macular mutant mouse as a model of Menkes kinky hair disease

Summary This study was undertaken to elucidate, using the Golgi method, the neuropathological change in the brain of the macular mutant mouse, whose hemizygote (Ml/y) is considered to be a model of Menkes kinky hair disease (MKHD). The hemizygote mice gradually lost weight after 10 days of age and died with emaciation and seizure around day 15. The normal littermate (+/y) was well developed. In the cerebrum, the arborization of pyramidal neurons in the layer V of the Ml/y was the same as that in the +/y on day 10. However, development of arborization in the Ml/y was delayed in comparison with that in the +/y on days 12 and 14. Purkinje cells with several somal sprouts were observed in the cerebellum in both the Ml/y and +/y on day 7. The somal sprouts in the +/y had regressed gradually by day 12, while they were still in the anterior and middle lobes of the Ml/y on day 14. Additionally, the trunks of Ml/y stem dendrites became thicker and a cactus formation was recognized on the branching portion of the dendrites on day 14. Arborization of these abnormal Purkinje cells was distinctly poor compared with that in the +/y. These results suggest that the growth of the neurons is delayed in the Ml/y and simultaneously their cytoskeletal developments are disturbed, especially in the Purkinje cells. There is a close similarity in many respects to the neuropathological change in MKHD.     

Usefulness of continuous air tonometry for evaluation of splanchnic perfusion during cardiopulmonary bypass

Although gastric mucosal tonometry has been reported as a useful method to assess splanchnic perfusion during cardiovascular surgery, the conventional discontinuous method of tonometry (saline tonometry) was cumbersome and prone to systematic errors. A new automated system of air tonometry (Tonocap; Datex Ohmeda, Helsinki, Finland) allows for frequent (every 10 minutes) measurement of gastric regional CO2 (PrCO2) and may be more suitable as a monitoring system in cardiac patients. We evaluated the usefulness of continuous air tonometry as a marker of splanchnic perfusion during cardiopulmonary bypass (CPB). In 19 patients (53-79 years, mean 63 years) who underwent cardiovascular surgery under standard CPB with mild hypothermia (32 degrees C) from January 2001 to May 2002, the PrCO2 and calculated intramucosal pH (pHi) of gastric tonometry was monitored using Tonocap, and their relation to postoperative visceral organ function was evaluated. The pHi significantly increased after initiation of CPB from 7.32 +/- 0.07 to 7.43 +/- 0.10 (p < 0.05) and then consistently decreased in all patients to 7.39 +/- 0.09 at the end of CPB. The value of PrCO2 significantly (p < 0.01) correlated with the value of pHi. The lowest value of pHi during CPB was significantly related to blood urea nitrogen (r = -0.75, p < 0.05), serum creatinine (r = -0.78, p < 0.05), creatinine clearance (r = 0.68, p < 0.05) on postoperative day 1, and blood urea nitrogen (r = -0.84, p < 0.01) on day 3. In contrast, arterial blood lactate level, venous oxygen saturation, and routinely measured hemodynamics (e.g., pump flow, arterial pressure) during CPB were unrelated to the postoperative visceral organ function. These results suggest that continuous monitoring of gastric regional CO2 and pHi by air tonometry system is useful for the evaluation of splanchnic perfusion during CPB and may contribute to improve CPB technique by allowing the early detection of visceral malperfusion.     

Molecular assembly of RNA polymerase II from the fission yeast Schizosaccharomyces pombe: subunit–subunit contact network involving Rpb5

Background: Eukaryotic RNA polymerase II is composed of more than 10 polypeptide chains. The minimum and essential subunits for RNA synthesis have not yet been identified. Toward this ultimate goal, we analysed the topological arrangement of the putative subunits. Here we report a subunit–subunit contact network involving subunit 5 of the fission yeast Schizosaccharomyces pombe RNA polymerase II.
Results: The rpb5 ⁺ gene encoding subunit 5 of RNA polymerase II was cloned from the fission yeast Schizosaccharomyces pombe . The polypeptide predicted from DNA sequence of the rpb5 ⁺ gene consists of  210 amino acids with a calculated molecular weight of 23 914. The homology of the amino acid sequence is 55% and 43% with Saccharomyces cerevisiae RPB5 and human hRPB25, respectively. Far-Western blot analysis of S. pombe RNA polymerase II using ³²P-labelled recombinant Rpb5 fused to glutathione S-transferase (GST) as a probe, indicated that Rpb5 binds strongly to membrane-immobilized Rpb1, Rpb2 and Rpb3 and weakly to Rpb5 and a 15-kDa subunit (Rpb8 or Rpb11). In agreement with this result, the ³²P-labelled Rpb3 probe showed a strong binding signal against Rpb5 in addition to Rpb1 and Rpb2. The existence of Rpb5–Rpb3 contact was supported by detection of complexes formed between these two proteins synthesized in vitro using protein-immobilized beads.
Conclusion: Rpb3 and Rpb5, the putative subunits of RNA polymerase II, associate each other to form binary complexes. These two subunits also bind to the two large subunits, Rpb1 and Rpb2, independently.     

Posthepatectomy hepatitis shortens tumor-free intervals in hepatitis C virus-associated hepatocellular carcinoma patients

In hepatitis C virus (HCV)-associated hepatocellular carcinoma (HCC), serum alanine aminotransferase (ALT) is frequently sustained on a high level after hepatectomy, with the formation of recurrent HCC tumors during follow-up periods. We investigated whether or not postoperative serum ALT level affects the interval before recurrence in hepatitis C virus-associated HCC. The subjects studied were 50 hepatectomized HCC patients who were HCV-Ab(+), and underwent a curable surgery in our Hospital from June 1990 to December 1999. We assessed the significance of the postoperative serum ALT level affecting tumor-free survival rates, as compared with other clinicopathological parameters, using univariate and multivariate Cox proportional hazard analysis. Thereafter, tumor-free and overall survival rates after hepatectomy were compared between high and low ALT groups, using Kaplan-Meier plotting and a log-rank test. The factor of ALT levels (a high or low ALT group) was most strongly associated with a tumor-free survival rate. Both tumor-free and overall survival rates were significantly poorer in the high ALT group than in the low ALT group among HCV-associated HCC cases (p<0.05). The results in this study suggest that postoperative hepatitis, which is indicated by sustained high ALT levels, may shorten the interval before recurrence in HCV-associated HCC. We should take care to control postoperative hepatitis to improve the prognoses of HCV-associated HCC cases.     

Accumulation of somatic hypermutation and antigen-driven selection in rapidly cycling surface Ig+ germinal center (GC) B cells which occupy GC at a high frequency during the primary antihapten response in mice

Well-developed germinal centers (GC) contain rapidly dividing surface immunoglobulin-negative (sIg^-) B cells (centroblasts), and most of their progeny are sIg⁺ B cells (centrocytes) in a resting state. It has been predicted that somatic hypermutation occurs in centroblasts, whereas antigen-driven selection takes place in centrocytes. The present analysis indicates that murine GC B cells bearing sIg with specificity for an immunizing antigen are in a rapidly cycling state and increase exponentially in number to occupy spleen GC at high frequency during the 1st week after primary immunization; however, the number of these cells is significantly reduced in the 2nd week of immunization. During that period, these proliferating sIg⁺ GC B cells accumulate somatic hypermutations with nucleotide exchanges indicative of affinity maturation. These sIg⁺ GC B cells co-express B7-2, ICAM-1, and LFA-1, and have potent antigen-presenting activity which results in T cell activation in vitro. These observations indicate that the sIg⁺ GC B cells accumulate somatic hypermutations and undergo antigen-driven selection through proliferation, probably upon activation by T cells. This sIg⁺ GC B cell population may represent cell cycling centrocytes; however, the possibility that these may represent centroblasts undergoing re-expression of sIg could not be excluded.     

The effect of androgen on the retention of extinction memory after conditioned taste aversion in mice

Conditioned taste aversion (CTA) induced by the application of a novel taste such as sodium saccharin (Sac) as the conditioned stimulus (CS) and a malaise-inducing agent as the unconditioned stimulus (US), results in acquisition of CTA memory to Sac. In contrast, CTA is extinguished by repeated presentations of the CS without the US, resulting in acquisition of the extinction memory. We examined the effects of androgenic hormones on acquisition and retention of extinction memory in mice. We gonadectomized sexually immature mice and continuously administered androgens to these animals. After sexual maturation, the mice underwent a conditioning period followed by an extinction period. Retrieval tests revealed that the androgen-treated group showed significantly greater retention of extinction memory than the non-treated group 5 weeks later, whereas such significant difference was not observed in acquisition of extinction memory. These results demonstrate the enhancing effect of androgens on retention of extinction memory.