The significance of Proliferating Cell Nuclear Antigen (PCNA) expression in cancer of the ampulla of vater in terms of prognosis

Seventeen patients with cancer of the ampulla of Vater were studied retrospectively using immunohistochemical staining with a monoclonal antibody to the proliferating cell nuclear antigen (PCNA). The relationships between the PCNA-positive rate, being the number of PCNA-positive cancer cells to total cancer cells, the clinicopathological findings, and the clinical course were evaluated. The PCNA-positive rate in patients with lymph node metastasis (47%) was significantly higher than that in patients without metastasis (29%), while that in patients with advanced cancer invading the pancreatic parenchyma (47%), was significantly higher than that in patients with early cancer without invasion of the sphincter of Oddi (32%). All of five patients with early cancer are still alive, whereas five with semi-advanced cancer invading the sphincter of Oddi but not the pancreatic parenchyma, and two with a PCNA-positive rate of over 40% died of recurrent cancer. Of seven patients with advanced cancer, only one with a low PCNA-positive rate of 23% is alive, but the other six with a PCNA-positive rate of over 40% all died. The results suggest that the PCNA-positive rate provides a prognostic index for cancer of the ampulla of Vater.     

Efficacy of HBIG and Hepatitis B Vaccine for the Prevention of HBV Transmission

The efficacy of HBIG and HB vaccine is summarized for the prophylaxis of HBV infection. Cases were divided into a “vertical” group of 130 neonates, consisting of 90 infants who received HBIG twice and then Hb vaccine from the second month after birth and HB vaccine beginning on the 5th day after birth (vertical II), and a “horizontal” group consisting of 108 infant who were given HB vaccine three times. In each case, excellent results were obtained and no adverse reaction was noted; however the number of cases who were not immunized was significantly higher and the member of chronic HBs-Ag carriers was higher in the vertical II group. the continuity of the immune state was fairly good for at least three years in the vertical I and horizontal groups. We think that in the case of the vertical group, the course of HB vaccine should be started in the second month after birth with the second inoculation of HBIG.     

Japan: Perspectives in School Health

In Japan, the original Law of School Health was established some 65 years ago to improve the environment and to prevent infectious diseases in school. Most recently, new environmental problems and behavioral issues have emerged. In addition to environmental health and health education, a major aspect of school health has been the development of a mass screening system both to detect present problems and to prevent adult diseases. In this article, the school health system in Japan is described and the application of mass screening by reference to heart disease as detected in Shimane Prefecture is illustrated. In the future, mass screening may be combined with a computer-based analysis system for managing data on new kinds of problems. New disciplines may become involved and improved programs developed, based on the lessons already learned from mass screening.     

Evaluation of the radiosensitizing effects of RK28 intravenous, intraarterial, and intratumoral injections on the rabbit VX2 tumor system

To evaluate the differences in the radiosensitizing effects of itnravenous (i.v.) injection, intraarterial (i.a.) injection, and intratumoral (i.t.) injections of the hypoxic cell radiosensitizer RK28 ([1-[4′-hydroxy-2′-butenoxy)methyl-2-nitroimidazole, 1 2-nitroimidazole with an acyclic sugar analogue substituted at the N-1 position of the imidazole ring) using an animal experimental syste.

Rabbit VX2 tumors, which were implanted in the muscle of left hind legs and grown to 3 cm in diameter, were treated with RK28 (80 mg/kg·b.wt) before 15 Gy of local x-ray irradiation. The auricular vein and the left saphenous artery were used for systemic injection and regional injection, respectively. For i.t. injection, a 21-gauge needle with three lateral holes was positioned in the central area of the tumor. Tumor regression was precisely evaluated by computed tomography (CT), and survival time was also studied. Using high-performance liquid chromatography (HPLC), pharmacokinetic studies for RK28 and its seven major metabolites were performed in tumor and serum at 0, 10, 20, 30, and 60 min after drug injection was completed.

Radiosensitizing effects of RK28 were considered present after i.a. injection (p < 0.05) and i.t. injection (p < 0.05) after analyzing tumor volumes on day 21 after treatment. Increased survival was not observed in any group with RK28 injection compared with survival in the group treated by x-ray irradiation alone. Pharmacokinetic studies showed the average concentration of RK28 in the tumor during x-ray irradiation was 1.3 times higher after i.a. injection and 3.5 times higher after i.t. injection than that after i.v. injection. The time modifying factor₅₀ (TMF₅₀:ratio of time for tumor to decrease by 50%, radiation alone vs. radiation plus drug) was calculated to be 1.5 after i.v. injection, 1.7 after i.a. injection, and 2.3 after i.t. injection. The values of TMF₅₀ correlated to the average concentrations of RK28 in the tumor. As to metabolites of RK28, β-glucoronated compound and cysteine conjugate were highly detected. The concentrations of cysteine conjugate were higher in the tumor than in serum via i.v. injection.

Radiosensitizing effects of RK28 were observed on the rabbit VX-2 tumor system after i.a. or i.t. injection. Pharmacokinetic studies proved that radiosensitizing effects depended on the concentration in the tumor, though the administration routes were different. Combined forms with nonprotein thiols were detected. However, survival benefits were not obtained by RK28. For clinical applications of RK28, i.a. or i.t. injection could facilitate better local of cancer.     

Expression of Oncogenes during Rat Chemical Hepatotumorigenesis Promoted by Estrogen

To elucidate the role of oncogene expression in hepatocarcinogenesis, we examined the expression of 4 cellular oncogenes (c -myc , c- fos , Ha- ras and c- erbA ) in liver tissues induced by chemical agents. Four groups of male Sprague-Dawley rats were examined in the present study. Rats of the first and second groups were given a single intraperitoneal injection of diethylnitrosamine (DEN), 200 mg/kg body weight. Two weeks later, these rats were divided into two groups; the DEN-C group received no further medication, whereas the DEN-DES group was given diethylstilbestrol (DES), 0.5 mg/day, for 12 months. The DEN group was given DEN, 100 ppm, in drinking water for five months as the hepatocellular carcinoma (HCC) group. The DES group was given DES, 0.5 mg/day, from the start for 8 months. Rats of the DEN-DES and DEN groups developed grossly visible hepatic tumors. Significantly higher levels of c- myc gene expression were observed in tissues of HCC of the DEN group and in neoplastic nodules of the DEN-DES groups than in the DES and DEN-C group. The increase of c -myc mRNA seemed to begin after 1 month of treatment and became significant at 4 months in the DEN-DES group. On the other hand, no significant differences in mRNA levels of c -fos, Ha- ras and c- erbA were observed among these four groups. Although the significance of increased c- myc gene expression in neoplastic liver is still not known, it is conceivable that the persistent elevation of c- myc gene expression in the DEN and DEN-DES groups might contribute to the development of rat chemical hepatotumori genesis.     

How far should we treat metastatic liver cancer? Report of three long-term survivors

The major issue in treating metastatic liver cancer is: how far should we perform resection? We believe that only reports of long-term survival afford an answer to this problem. We report three such patients. The first patient underwent pancreatoduodenectomy for cancer of the papilla of the duodenum and resection of metastatic liver cancer. She is alive without recurrence 15 years and 1 month after the initial surgery. The second patient received low anterior resection for rectal cancer, extended right lobectomy for liver metastasis, and pancreatoduodenectomy for metastasis at the common bile duct. She survived 6 years and 9 months after the initial surgery. The third patient underwent right nephrectomy for Wilms' tumor (adult type), extended right lobectomy for liver metastasis, and repeat resection of recurrences at the mediastinum and in the thoracic and abdominal walls. She is alive 21 years and 2 months after the initial surgery. These experiences have prompted us to carry out resection when surgery is deemed feasible.     

Factors affecting the bowel function after proctocolectomy and ileal J pouch-anal anastomosis for ulcerative colitis

The aim was to study determinants of postoperative bowel function after restorative proctocolectomy for ulcerative colitis. Medical records of patients who underwent proctocolectomy with ileal J pouch-anal anastomosis (IPAA) in two- or three-stage operations and whose status of defecation was known via a questionnaire were retrospectively reviewed. Bowel function, including stool frequency, stool consistency, and degree of nighttime soiling, was correlated with age at the time of surgery, time after ileostomy closure, mean resting anal pressure, longitudinal length of ileal J pouch, and duration of fecal diversion by using univariate and multivariate analyses. Stool frequency decreased significantly with time after ileostomy closure in both univariate and multivariate analyses. Stool frequency tended to be less in patients having a long J pouch, but the correlation was not significant (P=0.071) in univariate analysis. Nighttime soiling ameliorated with time after ileostomy closure in multivariate, but not univariate, analysis. Deterioration of nighttime soiling was seen in patients whose duration for fecal diversion was long, both in univariate (P=0.068) and multivariate (P=0.052) analyses. Stool consistency was related to none of the five factors investigated. These results indicate that as the time after surgery increases, stool frequency decreases and nighttime soiling ameliorates. Delaying ileostomy closure because of anticipated postoperative incontinence does not significantly alter postoperative continence.     

Effect of Intraperitoneal Injection of Mitomycin C Adsorbed on Activated Carbon Particles on Induction of Cytolytic Peritoneal Macrophages of Mice

The effects of the intraperitoneal injection of mitomycin C adsorbed onto activated carbon particles (MMC-CH) were assessed on the host immune status and the induction of cytolytic peritoneal macrophages (PM) in mice in comparison with an aqueous MMC solution (MMC-AQ). PM from inbred C57BL/6 mice and syngeneic B16 melanoma cells were used as the effector and target cells for the PM-mediated cytotoxicity assay. After a single injection of MMC-AQ (at the dose of 1/2 LD₅₀), the weights of thymus and spleen and the ³H-thymidine uptake of spleen cells stimulated by concanavalin A were markedly decreased compared to those following injection of MMC-CH containing the same dose of MMC. A significant difference was found in the chronological changes of peritoneal exudate cell (PEC) numbers and PM cytolytic activity between the MMC-AQ- and MMC-CH-treated mice. One day after MMC-AQ injection, the PEC numbers were decreased markedly. However, they increased ten-fold after MMC-CH injection and the PM cytolytic activity was significantly higher after MMC-CH injection than after MMC-AQ injection during the first 3 days. The present results suggest the possible superiority of MMC-coated charcoal over free MMC both because of a lessening of the effects on host immunity due to prolonged slow drug release and because of the increase in cytolytic macrophages that was induced.     

Identification of a novel GH isoform: a possible link between GH and melanocortin systems in the developing chicken eye.

GH is considered to play a role in the pathogenesis of diabetic retinopathy, causing neovascularization in the retina. The present study was conducted to assess the possibility that GH may play a role in ocular development by determining whether GH is expressed in the eye of the chicken during development. In the 17-d-old embryo, immunocytochemistry detected immunoreactive GH in retinal pigment epithelial (RPE) cells. Characterization of GH mRNA expressed in the eye by RT-PCR and rapid amplification of cDNA 5'-ends revealed it to be a novel GH mRNA transcribed from the middle of the intron 3 of the chicken GH (cGH) gene. The deduced protein, designated small GH isoform (s-cGH), was a cytosolic protein of 16.5 kDa with 140 amino acid (aa) residues, lacking the signal peptide and the N-terminal 71 aa residues of 22-kDa cGH, replacing them with 20 aberrant aa residues, and identical to 22-kDa cGH for the C-terminal 120-aa residue portion. Western blotting determined the molecular size of immunoreactive GH in RPE cells to be 80-84 kDa, similar to the computed molecular mass of s-cGH/GH receptor complex. Furthermore, RT-PCR demonstrated that GH receptor mRNA, but not s-cGH mRNA, was expressed in RPE cells. These results suggest that RPE cell is one of the target cells of s-cGH in the eye. During embryonic development, the immunoreactivity for s-cGH in RPE cells was initially observed on embryonic d 10, and the staining intensity increased and peaked on embryonic d 17. By hatching, s-cGH immunoreactivity in RPE cells was gradually decreased, and it was not detectable after hatching. This ontogenetic staining pattern correlates well with the pattern of the production of alpha MSH in RPE cells. The cell type expressing s-cGH remains to be identified; however, our findings imply a possible involvement of GH in the regulation of ocular development by acting on the intraocular melanocortin system in the chicken.