The immunohistochemical expression of BCL-2 oncoprotein in colorectal adenocarcinoma.

The immunoreactivity for bcl-2 oncoprotein was determined in tumor tissue samples from 40 patients with colorectal adenocarcinoma. Positive immunoreactivity for bcl-2 oncoprotein was seen in 14 of the 40 tumor tissue samples (35%) and was found to be associated with a significantly higher incidence of synchronous liver metastasis (P = 0.043); however, there was no correlation between the immunoreactivity for bcl-2 oncoprotein and tumor size, depth of tumor invasion, lymph node metastasis, or clinical stage of the disease. Among 33 patients who had undergone curative resection, disease-free survival did not differ significantly between 10 with bcl-2-positive tumors and 23 with bcl-2-negative tumors (P = 0.498). The present study showed that the positive immunohistochemical expression of bcl-2 oncoprotein was associated with a significantly higher incidence of liver metastasis from colorectal cancer, but it had no effect on the disease-free survival of patients who had undergone curative resection.

Toxic characteristics of the synthetic lipid A derivative DT-5461 in rats and monkeys.

We compared lethal toxicity and potential for splenomegaly and disseminated intravascular coagulation (DIC) of the lipid A derivative DT-5461 with those of compound 506 (C506) and bacterial lipopolysaccharide (LPS). These agents were given intravenously, by either bolus intravenous injection (2 ml/min) or drip infusion (3 ml/4 h), into the tail vein of rats under various regimens. In naive rats, the lethal dose after bolus intravenous injection was clearly higher than that after drip infusion for C506 and LPS, but not for DT-5461. In partially hepatectomized or D-galactosamine-treated rats, a marked enhancement of the lethality was observed for all agents relative to that in naive rats. Splenomegaly was commonly seen in all surviving rats after treatment, and histopathological examination revealed lymphoid hyperplasia in the B-cell area of the white pulp zone and lympho-reticular cell proliferation of the red pulp zone. When administered intravenously by drip infusion to rats pretreated with 0.4 M lactic acid, both C506 and LPS provoked DIC. This was manifested by a decrease in platelet counts, prolongation of activated partial thromboplastin time (APTT), and an increase in fibrin-fibrinogen degradation products (FDP), with hepatocellular necrosis and glomercular fibrin thrombus formation. In contrast, DT-5461 showed no such toxic events with the same protocol. In14-day intravenous toxicity studies of DT-5461, rats were more susceptible to hepatocellular necrosis and splenomegaly than squirrel monkeys. These results demonstrate that DT-5461 is a promising compound, with antitumor activity dissociated from its toxic potential.

Delivery of a normal newborn after intensive medical treatment for an acute exacerbation of ulcerative colitis during pregnancy: a case report.

A 28-year-old woman developed an acute exacerbation of chronic ulcerative colitis in the second trimester of pregnancy. She was treated by intensive medical treatment with intravenous prednisolone, betamethasone enema, oral salazosulfapyridine, intravenous ceftazitim, and total parenteral nutrition. The acute relapse subsided after 73 days of the treatment and a normal female newborn weighing 2,208 g was delivered vaginally after 40 weeks' gestation. Our experience showed that the intensive medical therapy did not impair either the course of the pregnancy or the fetal outcome.

Blood transfusion and postoperative serum interleukin-6 levels in colorectal cancer patients.

BACKGROUND/AIMS: Postoperative cytokine response affects various factors. However, excessive stress responses are deleterious as increased serum concentration of cytokines may induce tissue injury and an impaired immune system. METHODOLOGY: We determined serum IL-6 levels in 35 patients who had undergone resection of colorectal carcinoma. Eleven patients had a blood transfusion before or during the operation (transfused group) but 24 patients had received no blood transfusion (control group). Serum IL-6 levels were determined before the operation, and at the end of operation,POD-1, 3, and 7. RESULTS: There was no significant difference of preoperative mean levels of IL-6 between these two groups (p=0.20). Postoperative serum IL-6 levels were significantly elevated. Mean serum levels of IL-6 were significantly higher at the end of operation in the transfused group than in the control group (131.7 pg/ml in control group and 269.8 pg/ml in transfused group; p=0.02). CONCLUSION: The present study suggested that perioperative allogeneic blood transfusion can induce an excessive cytokine response and may be deleterious.

[Intravenous single dose toxicity of iodixanol, a new nonionic iso-osmolar contrast medium, in mice, rats and monkeys].

The single-dose intravenous toxicities of iodixanol, a new nonionic iso-osmolar contrast medium, were investigated in mice, rats and monkeys. The LD50 values were estimated to be 17.9 gI/kg for male mice and 16.2 gI/kg for female mice, 18.8 gI/kg for male rats and 22.0 gI/kg for female rats, and more than 10.0 gI/kg for monkeys. There was no marked sex difference in mice or rats, nor any significant difference observed between these two rodent species. Decrease in spontaneous locomotor activity, ptosis, respiratory depression and abdominal posture were observed in many mice and rats. These signs disappeared mostly by 8 days after dosing in surviving animals. Death occurred between immediately and 4 days after dosing in mice, and between immediately and 14 days after dosing in rats. Transient depression of body weight gain was observed in the surviving mice and rats by 7 days after dosing. Histological examinations revealed congestion or hemorrhage in the renal medulla, vacuolation or necrosis of the renal proximal tubular epithelium in mice and rats that died and vacuolation of the renal proximal tubular epithelium in surviving rats. There were no significant treatment-related changes in the laboratory and pathological examinations in monkeys.

Application of hematopoietic progenitor assays for the estimation of hematotoxicity in rats.

In a study to employ progenitor-derived clonogenic assays of granulocyte-macrophage colony-forming units (CFU-GM) and erythroid colony-forming units (CFU-E) for the assessment of chemically induced hematotoxicity in rats, we sought the appropriate culture medium for each assay. Then, the effect of cyclophosphamide or phenylhydrazine on bone marrow cells was examined in vivo and in vitro. Oral treatment of rats with 25 mg/kg of cyclophosphamide significantly decreased the number of CFU-GM, which was an earlier and more sensitive index than were other hematological parameters tested. Direct exposure of the culture to cyclophosphamide had little effect on CFU-GM production, but addition of sera from rats pretreated with cyclophosphamide strongly depressed their formation, which suggested that the active metabolites of cyclophosphamide produced in the body may play an important role in toxicity. Subcutaneous injection of rats with 40 mg/kg of phenylhydrazine produced a marked increase in CFU-E 6-24 hr after injection. Direct exposure of the culture to phenylhydrazine had severe cytotoxic effects, but addition of sera from rats receiving phenylhydrazine resulted in increased numbers of CFU-E, probably indicative of increases in endogenous erythropoietin in donor rats. These results demonstrate that the proper use of progenitor assays in the in vivo and in vitro studies may be a valuable tool for approaching the mechanism underlying hematotoxicity.

DNA ploidy, c-myc oncoprotein p62 and v-H-ras oncoprotein p21 in colorectal carcinoma.

DNA ploidy and expression of the c-myc oncoprotein p62 and the v-H-ras oncoprotein p21 were examined in 54 colorectal carcinomas. DNA ploidy, determined by DNA flow cytometry, was diploid in 19 samples and aneuploid in 35. Expression of the p62 oncoprotein, determined by immunohistochemical staining, was intensely positive in 18 samples while that of the p21 oncoprotein, also determined by immunohistochemical staining, was positive in 29. There was no correlation between DNA ploidy and expression of the p62 oncoprotein, and DNA ploidy did not correlate with expression of the p21 oncoprotein. There was, however, a close correlation between expression of the p62 oncoprotein and that of the p21 oncoprotein being P < 0.01 according to Peason's chi-square test.