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.     

Elevated expression of ETS-1 gene in a metastatic, tumorigenic human prostate epithelial cell line transformed by the v-Ki-ras oncogene

We investigated the inhibitory effects of intrasplenic combination therapy with OK-432 and recombinant interleukin-2 (IL-2) on liver metastasis of colorectal carcinoma. Intrasplenic administration group significantly inhibited the development of liver metastasis compared with subcutaneous administration group (p<0.05). Combination therapy significantly inhibited the development of subclinical liver metastasis compared with that in the control group. Combination therapy decreased the percentage of cells expressing CD8a, which may be a part of effective factors of combination therapy, and improved overall survival rate. These findings suggested intrasplenic combination therapy with OK-432 and IL-2 might be effective in inhibiting liver metastasis of colorectal carcinoma.     

Prevalence of second generation antibody to hepatitis C virus among voluntary blood donors in Osaka,Japan

To clarify the demographic characteristics of the prevalence of hepatitis C virus (HCV) infection in Osaka, Japan, where hepatocellular carcinoma is common, we investigated the screening data of antibody to HCV (anti-HCV, DAINABOTHCVPHA, second generation assay) in 197,600 voluntary blood donors residing in Osaka. The study found that age-standardized prevalence of anti-HCV was significantly higher than that of HBsAg (2.25cf 0.86 percent among males,P<0.001; 2.17cf 0.55 percent among females,P<0.001. It was much higher in the blood donors aged 55–64 years than in those aged 16–54 years (8.49cf 1.32 percent among males,P<10^–5; 7.26cf 1.42 percent among females,P<10^–5). The prevalence of anti-HCV among males was significantly higher than that of females in the younger (25–34 years) generations (1.02 to 1.49 percentcf 0.71 to 1.13 percent,P<0.05). A similar tendency was observed in the prevalence of high-titer (2¹²) anti-HCV. The number of coinfection (both HBsAg and anti-HCV seropositive) was very small, and it was not statistically different from the expected number.     

Effects of synchronous pulsatile extracorporeal membrane oxygenation in an endotoxin-induced shock model: an experimental study

A synchronous pulsatile venoarterial device for extracorporeal membrane oxygenation (ECMO) was designed to accomplish more effective circulatory support for neonates. The effect of this device was studied using an endotoxin-induced shock model, compared with conventional nonpulsatile ECMO. Twenty puppies weighing 1.6 to 4.0 kg were given endotoxin (5 mg/kg) intravenously. Thirty minutes after the administration of endotoxin, 10 were placed on pulsatile ECMO, and the others were placed on nonpulsatile ECMO, and they were studied for an additional 180 min. Peak blood pressure, arterial pH, base excess, and renal blood flow were significantly higher in the pulsatile group than in the nonpulsatile group. Serum lactate and serum noradrenaline were significantly lower in the pulsatile group than in the nonpulsatile group. These results indicate that pulsatile ECMO may provide more effective cardiopulmonary support in the treatment of neonates with serious circulatory failure that has failed to be supported by nonpulsatile ECMO.     

Hyperthermo-chemotherapy combined with cytoreductive surgery for the treatment of gastric cancer with peritoneal dissemination

Continuous hyperthermic peritoneal perfusion (CHPP) with anticancer agents (mitomycin C and cisplatin) in warm saline was performed in patients with peritoneal dissemination of gastric cancer following resection of the primary lesion. The effect of CHPP was examined by a second-look operation. This study includes 41 cases of gastric cancer with peritoneal dissemination but without liver metastasis treated during the past 6 years. The overall median survival was 14.6 months to 64.2 months from CHPP to death and the 3-year survival rate was 28.5%. Second look surgery revealed a remarkable diminution in the degree of peritoneal dissemination in 7 (50%) of 14 patients with disappearance of ascites after only one course of CHPP in 7 (77.8%) of 9 patients. Long-term 3 year-survival was noted in 4 (9.8%) patients on CHPP. Side effects were renal insufficiency in 2 (5%) patients, leukopenia in 2 (5%) patients, and perforation of the small intestine in 1 (2%) patient. These results suggest the effectiveness of CHPP in the treatment of gastric cancer with peritoneal dissemination.

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Resumen La perfusión hipertérmica continua (PHTC) con agentes anticancerosos (mitocina G y cisplatino) y solutión salina fue realizada en pacientes con cáncer gástrico con diseminación peritoneal después de resección de la lesión primaria, y el efecto de PHTC fue determinado mediante reexploración (operación de second look, OSL). La población de pacientes está constituída por 41 casos de cáncer gástrico con diseminación peritoneal pero sin metástasis hepáticas, tratdos en el curso de los últimos 6 años. La sobrevida media global fue de 437 dias (rango 28 a 1925 días) desde la PHTC hasta la muerte y la tasa de sobrevida a 3 años fue 28.5%. La OSL reveló una notoria disminución de la diseminación peritoneal en 7 (50%) de 14 casos y desaparición de la ascites después de sólo un ciclo de PHTC en 7 de 9 casos con ascitis. Sobrevida de 3 años ocurrió en 4 casos. Los efectos colaterales fueron insuficiencia renal en 2 casos (5%), leucopenia en 2 casos (5%) y perforación del intestino delgado en 1 caso (2%). Los anteriores resultados sugieren que la PHTC es eficaz en el tratamiento del cáncer gástrico con diseminación peritoneal.

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Résumé La perfusion péritonéale continue hyperthermique (PPCH) avec des agents anticancéreux comme le mitomycine C et la cis-platine avec sérum physiologique chauffé a été instaurée lorsqu'une carcinose d'origine gastrique a été trouvée. Les effets de la PCH ont été évalués chez 16 patients lors d'un second-look (SL). Cette étude concerne 41 patients avec carcinose péritonéale sans métastase hépatique observés au cours des 6 dernières années. La survie globale médiane était de 437 jours (extrêmes 28 à 1925 jours): le taux de survie a 3 ans était de 28.5%. Les lésions avaient diminué de façon notable chez 7 (50%) de 14 patients. L'ascite a disparu dans 7 des 9 cas. Une survie à long terme (3 ans) a été notée dans 4 cas. Les effets secondaires ont été une insuffisance rénale dans 2 cas (5%), une leucopénie dans 2 cas (5%) et une perforation de l'intestin grêle dans un cas (2%). Les résultats suggèrent que la PPCH est efficace dans le traitement du cancer gastrique avec dissémination péritonéale.

     

Effect of a selective inducible nitric oxide synthase inhibitor on intraocular nitric oxide production in endotoxin-induced uveitis rabbits: in vivo intraocular microdialysis study

Inducible nitric oxide (NO) synthase (iNOS) is believed to contribute to the pathogenesis of endotoxin-induced uveitis (EIU). In the present study, we investigated the inhibitory effects of N(G)-nitro-L-arginine methyl ester (L-NAME), a non-selective NOS inhibitor, and S,S'-1,4-phenylene-bis(1,2-ethanediyl)bis-isothiourea (PBITU), a potent and selective iNOS inhibitor, on intraocular NO production in EIU rabbits using an in vivo intraocular microdialysis technique. The flare level in the anterior chamber increased from 1h after the injection of 100 micro g/kg lipopolysaccharide (LPS), and continued to increase for 24h. Aqueous humor protein concentrations were significantly increased at 24h after LPS-injection. These changes were significantly reduced by L-NAME (10mg/kg) and PBITU (1mg/kg), but not by D-NAME (10mg/kg). The increase in NO(2)(-) and NO(3)(-) levels in the dialysate induced by LPS was significantly inhibited by L-NAME (10mg/kg) and PBITU (1mg/kg), but not by D-NAME (10mg/kg). These results suggest that activation of iNOS may play a key role in the development of EIU, and selective inhibitors of iNOS may have therapeutic applications in the treatment of EIU.     

Mesangial factor V expression colocalized with fibrin deposition in IgA nephropathy

BACKGROUND: Factor V in its active form (Va) plays a key role at the termination of the intrinsic coagulation pathway, serving as a membrane-bound cofactor for the conversion of prothrombin to thrombin by factor Xa. Cross-linked fibrin (XFb) is often observed in mesangial areas in active types of human glomerulonephritis. In this study, to clarify contribution of factor V in intramesangial coagulation, mesangial factor V expression and its relationship to mesangial proliferation and fibrin deposition in IgA nephropathy (IgAN) were investigated. METHODS: Twenty-two patients with IgAN were studied. XFb was detected in renal biopsy specimens using anti-d-dimer antibody combined with plasmin exposure, and factor V was detected with rabbit antibody against human factor V. Double-labeling immunohistochemistry was used to investigate the relationship of the glomerular distribution of factor V to XFb. The relationship of factor V staining to the activity index or XFb deposition was evaluated. The expression of factor V mRNA was assessed by in situ hybridization in relationship to the antigen staining of alpha-smooth muscle actin (alpha-SMA). The ultrastructural distribution of factor V in glomeruli was studied by immunoelectron microscopy. RESULTS: XFb and factor V were observed in the mesangium and along capillary loops in seven and nine specimens, respectively. Factor V had intense, frequent expression in the proliferating and necrotizing areas, showing a significant relationship to XFb (P < 0.05). Furthermore, XFb deposition and factor V expression were markedly correlated with disease activity (P = 0.005 and P = 0.008, respectively). By double-labeling experiments, XFb and factor V were often seen colocalized in mesangial areas of the glomeruli, which showed necrotizing lesions and/or intense cellular proliferation. By in situ hybridization, factor V mRNA was detected mainly in the mesangial cells, which were positive for alpha-SMA, and partly in the endothelial cells. By immunoelectron microscopy, factor V presence was confirmed in the mesangium and endothelium. CONCLUSION: The present findings suggest that factor V is strongly expressed in mesangial cells in active IgAN accompanied with mesangial proliferation and may exert procoagulant activity, leading to intramesangial coagulation.     

A case of epithelioid leiomyoma (leiomyoblastoma) of the urethra

A 25-year-old woman was admitted to our hospital because of a painless, slow growing mass arising from the external genitalia. The mass had been developing for a few years. She did not have difficulty voiding nor was there hematuria. Magnetic resonance imaging revealed a well-circumscribed, 4 cm, solid tumor between the urethra and the anterior vaginal wall. After needle biopsy confirmed a benign tumor arising from the smooth muscle, the tumor was removed by a transvaginal approach. The histopathological diagnosis was epithelioid leiomyoma (leiomyoblastoma), which often occurs in the stomach or uterus, but seldom around the urethra. The patient has remained well without recurrence for 20 months after surgery.     

A case of aconitine poisoning saved with cardiopulmonary bypass

"Torikabuto" is a kind of plant which contains deadly poison. Its ingredient is aconitine alkaloids. We report a case of aconitine poisoning with fatal arrhythmia and acute pulmonary edema who was saved with cardio pulmonary bypass. A 41-year-old male ate to mistake "Torikabuto" for wild plant. He developed symptoms of dysarthria and admitted to our hospital. He developed ventricular tachycardia and fibrillation soon after his admission. Then he developed cardiogenic shock. He was resuscitated and supported with a percutaneous cardio pulmonary bypass. Ventricular tachycardia disappeared 24 hours after admittion. About 1 week later, cardio pulmonary bypass was terminated and about 3 months later, he discharged from our hospital.     

A case of embolization to a large polycystic kidney with infection

75 year old female who was hospitalized for abdominal pain and fever up on 12th May 1998. She had been followed as a polycystic kidney patient since few years. The swelling of the right kidney and her general condition became gradually worse. On 18th May, the embolization to the right kidney using pure alcohol and gelatin sponge was performed. Within a month, CT scan showed the reduced volume of the right kidney and her blood examination data as well as her general condition became gradually well. And on 17th June, she left our hospital without any complication.