Cdc7 kinase is required for postnatal brain development

The evolutionally conserved Cdc7 kinase plays crucial roles in initiation of DNA replication as well as in other chromosomal events. To examine the roles of Cdc7 in brain development, we have generated mice carrying Cdc7 knockout in neural stem cells by using Nestin-Cre. The Cdc7^Fl/Fl Nestin^Cre mice were born, but exhibited severe growth retardation and impaired postnatal brain development. These mice exhibited motor dysfunction within 9 days after birth and did not survive for more than 19 days. The cerebral cortical layer formation was impaired, although the cortical cell numbers were not altered in the mutant. In the cerebellum undergoing hypoplasia, granule cells (CGC) decreased in number in Cdc7^{Fl/F l}Nestin^Cre mice compared to the control at E15-18, suggesting that Cdc7 is required for DNA replication and cell proliferation of CGC at mid embryonic stage (before embryonic day 15). On the other hand, the Purkinje cell numbers were not altered but its layer formation was impaired in the mutant. These results indicate differential roles of Cdc7 in DNA replication/cell proliferation in brain. Furthermore, the defects of layer formation suggest a possibility that Cdc7 may play an additional role in cell migration during neural development.     

Microsomal Cytochrome P-450 Monooxygenase System and Its Drug-metabolizing Activity after Partial Portal Vein Ligation in the Rat

RID=" ID=" <E5>Correspondence to:</E5> K. Izuishi, M.D.     

Relationship between striatal [123I]β-CIT binding and four major clinical signs in Parkinson’s disease

We investigated the correlation between clinical severity and striatal [123I]-CIT binding in 12 patients with Parkinson's Disease (PD: 6 men and 6 women, age: 65 +/- 7 years, Hoehn & Yahr stage: 1 to 3). The clinical severity of PD patients was measured with the Unified Parkinson's Disease Rating Scale (UPDRS) after withdrawal of antiparkinsonian medication at least 12 hours before assessment. [123I]beta-CIT binding in the caudate and putamen was measured at 3 hours [V'3 (day 1)], and at 24 hours [V'3 (day 2)) after tracer injection with small square ROIs. The specific striatal uptake index (day 2) was calculated with large square ROIs that encompassed the whole striatum. The best correlation (r = -0.82, p < 0.0012) was between putamenal V'3 (day 2) and the motor UPDRS scores. When the motor UPDRS scores were divided into four subscales, bradykinesia was the only sign that correlated significantly with putamenal V'3 (day 2) (r = -0.81, p < 0.002). [123I]beta-CIT SPECT is a useful marker of disease severity in PD with potential utility in the serial monitoring of disease progression.     

A pilot study of weekly paclitaxel administration for patients with relapsed cervical cancer after heavy medication

No standard therapy has been established for patients with relapsed cervical cancer after applying radical hysterectomies including lymphadenectomies, radiotherapy, and platinum-based chemotherapy. This study was designed to evaluate the effectiveness and safety of weekly paclitaxel (TXL) therapy in patients who suffered a cervical cancer relapse after heavy treatment. The candidates for the study included patients with cervical cancer that recurred after radical therapy (including lymphadenectomies), postoperative radiotherapy, and platinum-based chemotherapy, the lesions of which could be evaluated by imaging diagnosis. Patients received 80 mg/m2 of TXL by intravenous drip in one hour. Premedications included 10 mg of dexamethasone (iv), 50 mg of cimetidine (iv), and 50 mg of diphenhydramine (po) administered 30 minutes before the TXL treatment. This procedure was repeated weekly on an ongoing basis. The median progression-free survival was 14 months (range: 0 to 24 months), and the median overall survival 19 months (range: 6 to 24 months). Grade-3 or higer hematologic toxicity was observed for leukocyte (total WBC) and neutrophil/granulocyte in one patient (12.5%), but was controllable with GCSF. The weekly TXL therapy was effective against cervical cancer relapse after heavy treatment and its toxicity was tolerable.     

Single-stage repair for ascending aortic aneurysm,artery stenosis and occlusion of neck vessels caused by Takayasu arteritis

Takayasu arteritis results in a variety of vascular symptoms, and there are some cases in which progressive vascular lesions require surgical intervention. We present a case with ascending aortic aneurysm, right common carotid artery stenosis, left common carotid artery occlusion and left subclavian artery stenosis caused by Takayasu arteritis that was successfully treated with total arch replacement and ascending aorta to right internal carotid artery bypass.     

Quantification of N-acetyl-seryl-aspartyl-lysyl-proline in hemodialysis patients administered angiotensin-converting enzyme inhibitors by stable isotope dilution liquid chromatography-tandem mass spectrometry

We developed a sensitive, selective and accurate method based on liquid chromatography with tandem mass spectrometry (LC-MS/MS) to determine N-terminal thymosin-β peptides of Ac-SDKP and Ac-ADKP in human plasma samples. Quantification of Ac-SDKP and Ac-ADKP was performed using solid phase extraction (SPE) based on C(18), reversed phase LC separation, and stable isotope dilution electrospray ionization-MS/MS in multiple reaction-monitoring (MRM) mode. The Ac-SDKP-(13)C(6), (15)N(2) and Ac-ADKP-d(7) were synthesized for the internal standards. These MRM monitoring ions were m/z 488→129 (quantitative ion)/226 for Ac-SDKP, m/z 496→137 for Ac-SDKP-(13)C(6), (15)N(2), m/z 472→129 (quantitative ion)/226 for Ac-ADKP, and m/z 479→129 for Ac-ADKP-d(7), respectively. Lower limit of quantitation (LLOQ) of Ac-SDKP and Ac-ADKP was 0.1ng/mL in human plasma. Recovery values were ranged from 94.7% to 106.3% for inter- (RSD: 0.6-3.5%) and intra- (RSD: 0.4-4.9%) day assays. Plasma Ac-SDKP levels were significantly higher in hemodialyzed subjects treated with angiotensin-converting enzyme inhibitors of enalapril (27.3±24.6ng/mL, n=10) and trandolapril (12.3±16.9ng/mL, n=18) than healthy (0.4±0.2ng/mL, n=7) and hemodialyzed subjects (0.6±0.2ng/mL, n=34). This analytical method would be useful to measure N-terminal thymosin-β peptides in human plasma for the clinical study.     

Double stapling method for closure of intraoperative alveolar air leakage adjacent to the staple line: a randomized experimental study on ex vivo porcine lungs

BackgroundAlveolar air leakage from a pleural defect around the staple line is one of the complications after wedge resection of the lung. An intraoperative closure of the pleural defect by suturing can cause additional pleural rupture due to tension of the pleura adjacent to staple lines. Therefore, we have introduced a novel closure method for pleural defect adjacent to the staple line, named the double stapling method. This study compared the efficacy of two closure methods; the double stapling method and conventional suturing method with pledgets using ex vivo porcine lungs.MethodsThe double stapling method involves closing the pleural defect by suturing the two parallel staple lines at both sides of the pleural defect. This method was developed to distribute the pleural tension around the needle holes of suturing. As a model of pleural defect adjacent to the staple line after wedge resection, wedge resection of the caudal lobe of left porcine lungs was performed, and a superficial square pleural defect (10 mm × 10 mm) adjacent to the staple line was made by scalpel. The defect was closed using the following two methods: (I) suturing with pledgets (n=10); and (II) double stapling method (n=10). The lobe was inflated in water at an airway pressure of 20, 25, and 30 cmH₂O; closure success or failure was judged by the absence or presence of air leakage.ResultsThe closure success was confirmed in 2 (20%) out of 10 cases in the suturing with pledgets group and 9 (90%) out of 10 in the double stapling method group (P=0.007). In 4 out of 10 cases in the suturing with pledgets group, new pleural clefts longer than 3 mm were created around the needle holes of suturing.ConclusionsEx vivo experiments have suggested the superiority of the double stapling method for the intraoperative closure of alveolar air leakage adjacent to the staple line after wedge resection, compared to conventional suturing with the pledget method.     

猴脑杏仁体的认知功能

认知是脑的高级功能,其产生机制是脑科学的研究前沿之一。脑的认知功能涉及大脑皮质和皮质下的广泛脑区,不同部位涉及不同的认知类型。杏仁体（amygdala）是参与情绪性学习认知的重要结构。作者工作过的日本富山医科药科大学（现为富山大学医学部）研究生院系统情绪科学研究室长期从事杏仁体的认知功能研究,成绩卓著。本文综述了该研究室对猴脑杏仁体社会认知功能以及相关的最新研究成果,以飨读者。