Studies on chemical protectors against radiation. XXIX. Protective effects of methanol extracts of various Chinese traditional medicines on skin injury induced by X-irradiation

In order to investigate useful protective medicines for the relief of skin injury induced by irradiation, 60 methanol extracts of Chinese traditional medicines were used in the test of protective potency on skin injury. ICR male mice at 6 weeks of age were whole-body irradiated with 1100R by using a soft X-ray generator (30 kVp, 10 mA, 190 R/min). Each methanol extract of these medicines was injected intraperitoneally into mice before or after irradiation. The degrees of skin injury were determined by a score system of skin reaction within the observation period from 21st to 40th day after irradiation. Protective potency of each medicine on skin injury was calculated from the maximum mean scores of administrated group and un-administrated group. As a result of these studies, the protective potency was detected in Unsei-in, Kumibinro-to, Keisi-syakuyaku-chimo-to, Keigai-rengyo-to, Gosyuyu-to, Koso-san, Saiko-seikan-to, Syo-kankyo-to, Syo-saiko-to, Syoma-kakkon-to, Sen-kan-meimoku-to, Zokumei-to, Sokei-kakketu-to, Bokuryo-in, Mao-to and Rikkunsi-to by intraperitoneal injection before irradiation. Of these effective medicines, only Unsei-in and Mao-to are shown to have a significant protective effect by intraperitoneal injection after irradiation.     

Clinical experience of biliary tract carcinoma associated with anomalous union of the pancreaticobiliary ductal system

Between 1978 and 1988, 15 patients with gallbladder cancer and 2 patients with bile duct cancer were seen among 49 patients with anomalous union of the pancreaticobiliary ductal system. Radiographic findings revealed two types of this anomalous condition: one in which the pancreatic duct entered the common bile duct (type 1) and one in which the common bile duct entered the pancreatic duct (type 2). In gallbladder cancer, the common bile duct presented no dilatation, or in some patients, mild dilatation, and type-1 anomalous union was frequently found among these patients. In contrast, the two patients with bile duct cancer had cystic dilatation of the common bile duct and type-2 anomalous union. The bile amylase level, which was determined in seven patients, was extremely high in all the patients. Histopathologically, the tumors in most patients showed papillary to papillo-tubular proliferation in the mucosal layer while atypical epithelial hyperplasia was noted in the vicinity of the tumor area. These findings suggest that this congenital anomaly in both ducts results in a loss of the normal sphincteric mechanism of the duodenal papilla, and that chronic relapsing cholecystitis or cholangitis, caused by the reflux of pancreatic juice into the biliary tract, can induced progressive changes to atypical epithelial hyperplasia which may develop into carcinoma.     

The determination of thymidylate synthetase inhibition for testing fluoropyrimidines--pharmacokinetics and metabolism of carmofur (HCFU) in patients with gynecologic malignancies--Tokai HCFU Study Group for Gynecologic Malignancies

The pharmacokinetics and metabolism of carmofur (HCFU) were studied. Sixty-six patients were administered 100 mg of HCFU orally, and the plasma levels of the HCFU fraction (HCFUf) and 5-fluorouracil (5-FUra) were determined at 0, 1, 2, 4 and 6 hours. The average half-life of HCFUf and 5-FUra were 1.05 and 1.31 hours, and the average areas under the curves (AUC) of the plasma concentration were 6.51 hr X mcg/ml and 0.46 hr X mcg/ml, respectively. Surgical specimens of the tumors were obtained about three hours after the administration and assayed for HCFUf. 5-FUra fluorodeoxyuridine-monophosphate (FdUMP), deoxyuridine-monophosphate (dUMP), total thymidylate synthetase (TS total), and non-FdUMP-bound free enzyme (TS free). The TS inhibition rate (IR) was calculated by the follow method: IR = (TS total-TS free)/TS total X 100 levels of the TS total varied from not-detected (less than 0.10 pmol/g) to 20.5 pmol/g. The average FdUMP: dUMP ratio was 3.44 X 10(3), However, more than 80% inhibitions of TS were observed in nine cases (21.4%). The correlation indicates between TS IR and tissue FdUMP level or FdUMP: dUMP ratio were 0.57 and 0.62 in ovarian malignancies respectively. No significant correlations were observed between TS inhibition and levels of tissue 5-FUra or AUC of 5-FUra.     

Cloning and analysis of a gene (sms13) encoding sannamycin B-glycyltransferase from Streptomyces sannanensis and its distribution among actinomycetes.

A gene encoding sannamycin B-glycyltransferase (sms13) of Streptomyces sannanensis IFO 14239 was identified by cloning and complementation of S. sannanensis mutant SN13 which is blocked at the interconversion of sannamycins B and A. The cloned DNA fragment also permitted the conversion of fortimicin B to A both in S. sannanensis SN13 and Streptomyces lividans TK23. DNA sequences similar to sms13 were detected in all five producers of the fortimicin-group antibiotics, Micromonospora olivasterospora ATCC 21819 (fortimicin-producer), Micromonospora sp. strain SF-2098 ATCC 31580 (SF-2052), Dactylosporangium matsuzakiense ATCC 31570 (dactimicin), Streptomyces tenjimariensis ATCC 31603 (istamycin), and Saccharopolyspora hirsuta ATCC 20501 (sporaricin). This suggests that these genes of similar function from different genera were derived from a common ancestral gene.     

Experimental model of chronic tonsillar herniation associated with early stage syringomyelia

This report describes an experimental model of chronic tonsillar herniation and its effects on the spinal cord. In ten rats, a small piece of chemically induced mammary cancer was transplanted to the supraoccipital bone. In all cases, the transplanted cancers grew into the posterior fossa, destroying the supraoccipital bone and compressing the cerebellum extradurally. In six of the ten rats, tonsillar herniation was observed at 8–14 weeks after transplantation. Transdural infiltration of the tumor cells was not apparent in any animal. In those rats with tonsillar herniation (n=6), the spinal cord from the C5 to the T8 segments showed enlargement of the central canal without exception. Histological examination revealed the following changes: stretching and thinning of the ependymal cells; swelling of the astrocytic processes; and extracellular edema, predominantly in the dorsal gray matter, but also in the ventral inner portion of the dorsal column. In the control group (n=4) and those rats without tonsillar herniation (n=4), such histological changes of the spinal cord were not observed. Although the lesions can not be regarded as representing mature syringomyelia, they most likely constitute an earlier evolutionary stage.     

Comparison of DNA fingerprinting by PFGE and PCR-RFLP of the coagulase gene to distinguish MRSA isolates

Staphylococcus aureus isolates were collected from epidemiologically unrelated clinical sources in Japan between 1991 and 1993. A total of 40 isolates, five each of eight coagulase types, were analysed by polymerase chain reaction (PCR) of the coagulase gene, PCR-restriction fragment length polymorphism (RFLP) after AluI digestion, and pulsedfield gel electrophoresis (PFGE) of chromosomal DNA after SmaI digestion. The efficiency of discrimination among the isolates increased in the order of PCR < PCR-RFLP < PFGE, yielding five, 13 and 31 different types, respectively. To assess the clinical use of these methods, 42 additional methicillin-resistant S. aureus (MRSA) isolates collected from 27 inpatients in a hospital were analysed. PFGE and PCR-RFLP were able to discriminate 11 and four types, respectively. PFGE analysis detected cross-infection between four postoperative patients in an intensive-care unit, and in six neonates in intensive care. We conclude that of the three methods tested, PFGE analysis currently allows the most effective discrimination of MRSA strains.     

Development of new immunoradiometric assay for CA 125 antigen using two monoclonal antibodies produced by immunizing lung cancer cells

CA 125 is an antigen associated with non-mucinous epithelial ovarian cancer, which is defined by OC 125 antibody developed by immunizing ovarian cancer cells. We have produced two monoclonal antibodies, 130-22 and 145-9, by using the human lung adenocarcinoma cell line PC-9. Both 130-22 and 145-9 antibodies recognized CA 125 antigen. However, the binding sites seemed to be separate from those of OC 125. Testing by 9 immunoradiometric assays (IRMA), using different combinations of the 3 monoclonal antibodies 130-22, 145-9 and OC 125 demonstrated that the best standard curve for detecting CA 125 could be obtained by a "simultaneous sandwich" assay based on a mixture of 125I-labeled OC 125 and 130-22 or 145-9 coated beads. One-step IRMA, using 130-22 as a tracer and 145-9 as an immunoadsorbent, also showed good reproducibility and sensitivity for measuring CA 125. Antigens were detectable in the culture supernatants of PC-9 cells and 5 of 6 ovarian cancer and endometrial adenocarcinoma cells. These results indicate that one-step IRMA using 130-22 and 145-9 is useful for detecting CA 125 antigen.