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.     

Analysis of Cdc2 and Cyclin D1 expression in breast cancer by immunoblotting

Cyclins and cyclin-dependent kinases may reflect the status of cell proliferation in cancer tissues. The authors sought to determine whether cdc2 and cyclin D1 are expressed in breast cancer and are useful as prognostic factors. Accumulation of cdc2 and cyclin D1 proteins was examined in 88 cases of breast cancer using immunoblotting techniques and correlations with clinicopathological factors and prognoses were investigated. Cdc2 and cyclin D1 proteins were observed in 27.3% and 75.0% of breast cancers studied, respectively. The incidence of lymph node metastasis was significantly high in cdc2/cyclin D1-double positive group and low in double negative group. On the other hand, the incidence of estrogen receptor (ER) negative cases was significantly higher in the cdc2-positive/cyclin D1-negative group. Relapse-free survival times of cdc2-positive cases were significantly shorter than those of cdc2-negative cases. The relapse-free survival times of cyclin D1-positive cases also tended to be poorer than those of cyclin D1-negative cases. Multivariate analyses revealed cdc2 as the second most significant of the prognostic variables, following lymph node status. The three-year relapse-free survival rate of cdc2/cyclin D1-double positive cases was 58.9%, whereas that of cdc2/cyclin D1-double negative cases was 100%. Cdc2 and cyclin D1 represent the status of cell proliferation in breast cancer, and may be useful in breast cancer assessment.     

p53 mutations of lung cancer are not significantly affected by CYP1A1 or GSTM1 polymorphisms

Cytochrome p4501A1 gene (CYP1A1) and glutathione S-transferase mu gene (GSTM1) are involved in the metabolic activation or detoxification of environmental carcinogens including benzo[a]pyrene in tobacco smoke. Individuals with both Val/Val and C type of CYP1A1 (CYP1A1; Val/Val and CYP1A1; C) or homozygous null (-/-) genotype of GSTM1 gene (GSTM1; -/-) show increased susceptibility to lung cancer. The incidence of p53 gene mutations are related to the smoking index of the lung cancer patients. Therefore we determined genotypes of these enzymes and screened p53 gene mutations in 123 non-small cell lung cancer (NSCLC) patients. p53 gene mutations were found in 35% (43/123) of the patients. The incidence of p53 gene mutation CYP1A1; Val/Val (60.0%), CYP1A1; C (50.0%) tended to be higher than those of CYPIAI; Ile/Ile and Ile/Val (40.4%) or CYP1A1; A and B (40.5%). We conclude that the incidence of the p53 mutations does not seem to be significantly affected by only CYP1A1 or GSTM1 polymorphisms in lung cancer patients.     

Nuclear medicine Competitors or collaborators?

Here in the USA

Nuclear medicine Competitors or collaborators?     

Remaining solvents in dry cleaned over clothes]

We examined remaining solvents in dry cleaned trousers to estimate the magnitude of environmental pollution. A cleaning solvent of petroleum hydrocarbon was analyzed by means of capillary column mass spectrum gas chromatography. Principal ingredients were identified to be nonane, decane and undecane. The same main components were detected in dry cleaned trousers. Total amounts of evaporated vapor from a pair of trousers (480 g) in 5 days after dry cleaning were nonane (0.73 mg), decane (1.53 mg) and undecane (1.09 mg). The levels on the fifth day were 5%(nonane), 18%(decane) and 32%(undecane) of the first day's concentration, respectively. The half times of the remaining solvents were 1.0 day (nonane), 1.7 days (decane) and 2.7 days (undecane), respectively.     

Pseudomembranous colitis: spectrum of imaging findings with clinical and pathologic correlation.

Pseudomembranous colitis (PMC) is a potentially life-threatening acute infectious colitis caused by one or more toxins produced by an unopposed proliferation of Clostridium difficile bacteria. PMC is characterized by the presence of elevated, yellow-white plaques forming pseudomembranes on the colonic mucosa. These plaques can be visualized at both pathologic analysis and endoscopy. Plain radiography, contrast enema studies, and computed tomography (CT) are useful in the evaluation of PMC. Plain radiography of the abdomen can demonstrate polypoid mucosal thickening, "thumbprinting" (wide transverse bands associated with haustral fold thickening), or gaseous distention of the colon. A toxic megacolon with distention and occasionally pneumoperitoneum may be seen in the most severe cases of PMC involving perforation. At contrast enema studies, the primary finding in mild cases of PMC is small nodular filling defects representing the mucosal plaques. With more extensive colonic involvement, the plaques are larger and coalesce to form an irregular bowel wall margin. Mural thickening and wide haustral folds caused by intramural edema may also be seen. A contrast enema study is contraindicated in patients with severe PMC due to the danger of perforation. Common CT findings include wall thickening, low-attenuation mural thickening corresponding to mucosal and submucosal edema, the "accordion sign," the "target sign" ("double halo sign"), pericolonic stranding, and ascites. Familiarity with these imaging characteristics may allow early diagnosis and treatment and prevent progression to more serious pathologic conditions.     

Correlation of tensile strength with bursting pressure in the evaluation of intestinal anastomosis

BACKGROUND: Although bursting pressure and tensile strength have long been measured to evaluate anastomotic techniques, it has yet to be clarified whether or not they are correlated, what implications they have, and which should be used as a gold standard. MATERIAL AND METHODS: Using an experimental model to estimate pressure and tension in the same colonic anastomosis, the following variables were measured in 48 rats between days 0 and 14: bursting pressure (BP); minimal tensile strength (MITS) necessary to break a part of the anastomosis, and maximal tensile strength (MATS) needed to disrupt the whole anastomosis. Also, circulatory wall tension (CWT) was derived from BP and the anastomotic circumference (AC), and longitudinal wall tension (LWT) from MITS and AC. These variables were compared using correlation and regression analysis. RESULTS: During the lag phase (days < or = 4) there was poor correlation between pressure-related and tension-related variables whereas highly significant correlations were noted in the subsequent fibroplastic phase (day > or = 5). It was shown by regression lines that positive MITS and MATS were expected when BP was zero. CONCLUSION: Contrary to the previous assumption, no correlation was found between BP and tensile strength in the critical postoperative period. Based on our present and previous studies, measurement of MITS is recommended to evaluate the healing of colonic anastomosis.     

Aesthetic Male Facial Skeletal Surgery

Craniofacial surgery concepts developed originally for reconstruction may also be applied to aesthetic surgery. The facial skeleton is an important component of appearance and may be modified using common craniofacial surgery techniques. Three representative male patients are presented, who each desired an improvement in his appearance. The techniques used were different and combined orthognathic and remodeling procedures. Aesthetic male facial skeletal surgery was beneficial in these selected cases. The results were well received and without complications. Surprisingly, we have found that male skeletal aesthetic patients did not have unrealistic expectations and were pleasant to manage pre- and postoperatively.     

Gamete development inPlasmodium berghei regulated by ionic exchange mechanisms

Ionic regulation in the induction of exflagellation ofPlasmodium berghei was investigated by culturing the parasites in various isotonic media. Of the salts tested, NaHCO₃ exhibited the highest activity in inducing exflagellation, whereas KHCO₃ showed no activity. In the absence of HCO ₃ ^– , media containing monovalent cation (Na⁺, K⁺, Cs⁺, Rd⁺, choline⁺, lysine⁺, arginine⁺) and Cl^– also induced exflagellation, but their activities were lower than that of NaHCO₃. Anions of Br^– or NO ₃ ^– could be substituted with Cl^–, whereas other anions such as I^–, NO ₂ ^– , SO ₄ ^2– , SCN^–, H₂PO ₄ ^– , or HPO ₄ ^2– failed to induce exflagellation, as did tetramethylammonium-Cl, CaCl₂, MgSO₄, MgCl₂ and sucrose as well. These results suggest that the induction of exflagellation requires the presence of Na⁺ and HCO ₃ ^– or monovalent, membrane-permeable cation and Cl^– in the medium. Measurements of the efflux of H[¹⁴C]O ₃ ^– or Cl^– indicated that these anions were released from the cells into the NaCl or the NaHCO₃ medium, respectively, probably by exchange in HCO ₃ ^– /Cl^–. Determination of intracellular ionic concentrations by electron microscopic X-ray microanalysis of cryopreserved specimens revealed that in the NaHCO₃ medium, external Na⁺ (and probably HCO ₃ ^– ) enters the gametocytes by exchange with internal Cl^– (and probably H⁺), whereas in Cl^–-containing media, external unspecified cation and Cl^– influx by exchange, probably with H⁺ and HCO ₃ ^– . It is therefore suggested that two separate ion exchangers, i.e., Na⁺-dependent HCO ₃ ^– (in)/Cl^–(out) and nonspecific monovalent-cation-dependent Cl^–(in)/HCO ₃ ^– (out) exchangers, are involved in the induction of gametogenesis inP. berghei. Furthermore, the presence of both classes of anion in the medium enhanced exflagellation activity and increased Na⁺ uptake more than did the NaCl or NaHCO₃ medium alone. The apparent synergistic enhancement by two contraactive anion exchangers is consistent with a recycling model of pH_i regulation, in which HCO ₃ ^– and Cl^– are exchanged between the cells and the media, resulting in the acceleration of monovalent cation/H⁺ exchange.This work was supported by a Grant-in-Aid (No. 01570212) from the Ministry of Education, Science and Culture, Japan and the Ohyama Health Foundation, Japan (to FK), and in part by the Medical Research Council, United Kingdom (to RES)