Monoclonal Gammopathy in Adult T-Cell Leukemia/ Lymphoma: A Report of Three Cases

Adult T-cell leukemia/lymphoma (ATL/L) is clustered in southwesternJapan, especially in the Nagasaki and Kagoshima areas. It wasshown that this clustering correlated with the presence of antibodiesto antigens of a new C-type RNA leukemia virus. Surface markeranalysis of neoplastic T-cells of ATL/L patients shows the helper/inducerphenotype (Leu-1⁺, Leu-2a^– and Leu-3a⁺). On the other hand, the association between T-cell malignancyincluding ATL/L and monoclonal gammopathy is very rare. Threeunique cases of ATL/L with monoclonal gammopathy are reported.Yet the meaning of an M-component in T-lymphocytic proliferationremains uncertain. The relationship between the leukemia virus,ATL/L-cells and monoclonal gammopathy is discussed.     

Novel HER2 selective tyrosine kinase inhibitor, TAK-165, inhibits bladder, kidney and androgen-independent prostate cancer in vitro and in vivo

PURPOSE: TAK-165 is a new potent inhibitor of human epidermal growth factor receptor 2 (HER2) tyrosine kinase. Several reports suggest HER2 expression in bladder cancer, renal cell carcinoma (RCC) and androgen-independent prostate cancer. We therefore investigated the antitumor effect of TAK-165 on these urological cancer cells. MATERIALS AND METHODS: Western blot analysis was performed to confirm HER2 expression in cell lines. To study in vitro efficacy, cells were treated with TAK-165 at various concentrations for 72 h and then counted using a hemocytometer. Then the IC50 value was calculated. In the xenograft model, after the tumor reached 200-300 mm3 in volume, mice were orally administered TAK-165 10 mg/kg per day or 20 mg/kg per day or saline for 14 consecutive days (n=6-8). RESULTS: HER2 expression was observed in HT1376, UMUC3, T24 (bladder), ACHN (kidney), DU145, LNCaP, LN-REC4 (prostate), although the expression level in these cells was weak compared with BT474 (a breast cancer cell line which expresses HER2 strongly). IC50 was varied from 0.09 to greater than 25 micromol/L in the bladder cancer cell line. ACHN cells were less sensitive in vitro. The prostate cancer cell lines studied were all sensitive (IC50 0.053-4.62 micromol/L). In the xenograft model, treatment with TAK-165 significantly inhibited growth of UMUC-3, ACHN, and LN-REC4. The antitumor effect (T/C [%]=growth of TAK-165 treated tumor/average growth of control tumorx100) after 14 days treatment were 22.9%, 26.0%, and 26.5% in UMUC3, ACHN and LN-REC4, respectively. CONCLUSIONS: TAK-165 may be a hopeful new agent for bladder, kidney and androgen-independent prostate cancer.     

The novel histamine H2 receptor antagonist FRG-8813 prevents delay of wound repair induced by hydrogen peroxide in a rabbit gastric epithelial cell system

Abstract The effects of a novel histamine H₂ receptor antagonist (FRG-8813) on the restoration process of gastric epithelial wounds were assessed using an in vitro wound healing model. FRG-8813 (1, 10 mol/L) was added to a complete confluent monolayer cell sheet after artificial wounding. The restoration process was analysed by a time-lapse video system and cell migration, proliferation and apoptosis were assessed. Hydrogen peroxide (1, 3 mmol/L) inhibited restoration after wounding by suppressing cell migration and proliferation and induced epithelial cell apoptosis around the wound. The addition of FRG-8813 abolished the hydrogen peroxide-induced retardation and prevented apoptosis, although FRG-8813 itself did not enhance wound healing. FRG-8813 may act as a radical scavenger as well as having an anti-secretory action and may have favourable effects on peptic ulcer healing.     

Prognostic value of nuclear area index in patients with bladder cancer

BACKGROUND: To assess the prognostic usefulness of the nuclear area index (NAI), a new nuclear morphometric parameter expressed as the mean nuclear area (MNA) ratio of cancer to normal transitional cells in patients with bladder cancer, who have undergone radical cystectomy. METHODS: Measurements of the nuclear areas of cancer and normal transitional cells were carried out on the histological slides of 73 patients with bladder cancer. The clinical usefulness of MNA, NAI, grade, and TNM categories for the prediction of the cause-specific survival of the patients was examined. RESULTS: The median values of MNA and NAI in the 73 patients were 39 micro m2 and 1.2, respectively. Cause-specific survival rates of the patients were calculated according to stage (T1-2 vs T3-4), grade (grade 2 vs grade 3), MNA (<39 micro m2 vs>/=39 micro m2) and NAI value (<1.2 vs>/=1.2). Using univariate analysis, all these parameters were statistically significant prognostic factors. However, by multivariate analysis, NAI was the only independent variable for the survival of the patients (P < 0.01). Cause-specific survival rates of patients with NAI values of less than 1.2 were significantly higher than those with NAI values of 1.2 or more, in both grade 2 and grade 3 tumors. CONCLUSIONS: These results suggest that NAI could provide improved prognostic information for patients with bladder cancer.     

Babesia Microti感染鼠对Babesia Rodhaini再感染交叉免疫保护机理的研究

目的研究Babesia Microti和Babesia Rodhaini感染的交叉免疫保护作用,以探讨B.Microti和B.Rodhaini不同种属之间是否存在交叉保护及保护机制。方法首先制备Babesia Microti感染耐过鼠,再用Babesia Rodhaini进行再感染,分别于B.Rodhaini再感染后的12、24、48、72h,使用ELISA方法分别检测血清中IL-12及IL-10的浓度,并同时检测寄生虫血症、网织红细胞变化、致死率与死亡时间。结果B.Microti感染耐过鼠再感染Babesia Rodhain后24h,小鼠血液中IL-12较未感染组及B.Microti感染耐过鼠明显增高,而血液中IL-10水平在再感染后72h时与对照组比较差异显著。B.Microti感染耐过鼠再感染Babesia Rodhain后,血液中出现一过性寄生虫血症,实验鼠可完全耐过。结论B.Microti感染耐过鼠可完全保护B.Rodhain的再感染,其细胞因子的产生为IL-12早于IL-10。     

Electrophysiology of the Atrio-AV Nodal Inputs and Exits in the Normal Dog Heart

Ablation of Atrionodal Connections. Introduction : We studied the effects of selective and combined ablation of the fast (FP) and slow pathway (SP) on AV and VA conduction in the normal dog heart using a novel epicardial ablation technique.
Methods and Results : For FP ablation, radiofrequency current (RFC) was applied to a catheter tip that was held epicardially against the base of the right atrial wall. SP ablation was performed epicardially at the crux of the heart. Twenty-three dogs were assigned to two ablation protocols: FP/SP ablation group (n = 17) and SP/FP ablation group (n = 6). In 12 of 17 dogs, FP ablation prolonged the PR interval (97 ± 10 to 149 ± 22 msec. P < 0.005) with no significant change in anterograde Wenckebach cycle length (WBCL), Subsequent SP ablation performed in 8 dogs further prolonged tbe PR interval and the anterograde WBCL (117 ± 22 to 193 ± 27, P < O.(M)5). Complete AV block was seen in I of 8 dogs, whereas complete or high-grade VA block was seen in 6 of 8 dogs. In the SP/FP ablation group, SP ablation significantly increased WBCL with no PR changes. Combined SP/FP ablation in A dogs prolonged the PR interval significantly, but no instance of complete AV block was seen. VA block was found in 50% of these cases. Histologic studies revealed that RFC ablation affected the anterior and posterior atrium adjacent to the undamaged AV node and His bundle.
Conclusion : Using an epicardial approach, combined ablation of tbe FP and SP AV nodal inputs can be achieved with an unexpectedly low incidence of complete A V block, although retrograde VA conduction was significantly compromised.     

Effect of ageing on pancreatic hyperplasia after 90% proximal small bowel resection

The present study was performed to examine the effect of ageing on pancreatic hyperplasia observed after proximal small bowel resection (PSBR). Young and old Wistar rats were randomly assigned to two groups, which underwent either an approximate 90% PSBR or a jejunal and ileal transection (TRC). One week after the operation, the pancreatic wet weight and the protein, DNA and RNA content of the pancreas were all significantly higher in young PSBR rats than in young TRC rats. However, no differences were seen in the old rat groups. Plasma enteroglucagon levels were elevated in both young and old PSBR rats, but the ratio of increase between the PSBR and TRC groups was significantly higher in young rats. Plasma cholecystokinin and gastrin levels did not increase after PSBR in either the young or old rats. These findings suggest that pancreatic hyperplasia observed after PSBR is attenuated by ageing, probably due to an insufficient increase in plasma enteroglucagon levels.