Isolation of salmonellae from clinically normal cattle and pigs in Indonesia in 1986 and detection of plasmids in the isolates.
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Biomedical subjects
Publications and source records attributed to N Nakashima.
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The multiplicity of the spontaneous lung tumor in CD-1 mice was investigated in 413 males from 6 different control groups of 2-year carcinogenicity studies with agrochemicals. Among a total of 152 lung tumor bearers, 95 (62.5%) were seen with 1 nodule, 36 (23.7%) with 2 nodules, and 14 (9.2%) with 3 nodules. Three males bore 4 nodules and each of 5, 7, 9 and 10 nodules was seen in one male, respectively. In one control group 20 out of 30 lung tumor bearers had 2 or more nodules presenting a significant heterogeneity among the control groups in terms of the multiplicity of lung tumor nodule.
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Dermatan sulfate proteoglycan chains were detected in tissue sections treated with chondroitin B-lyase (0.01 units/ml) in 20 mM Tris-HCl (pH 8.0) for 1 hr, followed by staining with antibody 9A2 specific for unsaturated uronic acid coupled to N-acetylgalactosamine-4 sulfate. In contrast, after treatment with chondroitin B-lyase, no positive staining was observed with antibodies 3B3 and 1B5 which react to the unsaturated uronic acid coupled to N-acetylgalactosamine 6-sulfate and unsaturated uronic acid coupled to N-acetylgalactosamine, respectively. The distribution of dermatan sulfate thus revealed was confirmed by comparison with that found by monoclonal antibody 6B6 which reacts with small proteoglycans carrying dermatan sulfate side chains. The localization of positive staining in fibrous connective tissues was almost identical with these two procedures.
Mouse bone marrow cells were seeded on small pieces of cover glasses placed in culture dishes, and after 3 days, the pieces of glass to which only small spindle cells adhered were transferred to another dish containing fresh medium. The adherent small spindle cells proliferated and some of them became large polygonal cells with abundant cytoplasm. When phenyl beta-D-thioxyloside (0.5 mM), an artificial initiator of chondroitin sulfate chain synthesis, was added to the culture medium, the cells showed a marked increase in number as compared to controls, with conversion of about 35% of the cells to large size cells. Immunohistochemical staining with monoclonal antibodies showed that the intercellular matrix of adherent cells consists mainly of a large proteglylcan with chondroitin 6-sulfate side chains. By histochemical analysis, the amount of chondroitin sulfate was shown to be greater in the intercellular matrices of xyloside-treated groups than those of control cultures. The amount of chondroitin sulfate in the growth medium of the adherent cells, as measured by uronic acid analysis, was also significantly increased by treatment with phenyl beta-D-thioxyloside compared with controls.
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Twenty patients with bladder cancer were treated with intra-arterial infusion chemotherapy using CDDP and ADM in combination with [Sar1, Ile8] angiotensin II. A catheter was introduced into internal iliac artery by Seldinger's technique, and 100 mg of CDDP, 50 mg of ADM and 1 mg of [Sar1, Ile8] angiotensin II were infused through the catheter for 40 minutes. CR was observed in 8 of 20 patients. PR in 11 and NC in 1. Therefore, the response rate (CR + PR) was 95% (19/20). Side effects were generally mild and consisted of leukopenia, nausea, vomiting, diarrhea, alopecia, skin pigmentation and headache. Catheter-related complications were not observed. This study demonstrated that intra-arterial infusion chemotherapy with CDDP and ADM in combination with [Sar1, Ile8] angiotensin II was extremely effective in treating patients with bladder cancer.
Three mouse IgG1 monoclonal antibodies (MoAbs) reactive predominantly with cytoplasmic antigens of mucinous type ovarian tumors were produced. OM-A MoAb was reactive with 11 of 14 mucinous type and two of three endometrioid type ovarian tumors, although only a minor population of the tumor cells was positive in the latter type. This MoAb was not reactive with serous type, clear cell type, or other types of ovarian tumors, nor with various types of uterine carcinoma. Normal adult and fetal tissues of female genital organs were not positive with this MoAb. Among nongynecological carcinomas, three of six metastatic tumors to the ovary from the gastrointestinal tract, one of five gastric carcinomas, and one of eight lung adenocarcinomas were positive. As for normal adult and fetal tissues of nongynecological origin, epithelium of the normal stomach, small bowel, and bronchus as well as epithelium of fetal small and large bowel and secretory products were weakly positive. Thus, this MoAb showed a selected specificity against mucinous and endometrioid types of ovarian tumors. OM-B MoAb showed a broader specificity than OM-A, reacting with all mucinous type, two of three endometrioid type, and three of 16 serous type ovarian tumors, but not with clear cell type tumors. Adenoma type, but not squamous type, cervical carcinomas and one-half of endometrial carcinomas were positive. This antigen is present in cervical mucosa, but not in ovary or endometrium. OM-C MoAb showed a specificity similar to, but broader than that of, OM-B; i.e., 11 of 14 mucinous type, two of three endometrioid type, nine of 16 serous type, and one of nine clear cell type ovarian tumors were positive. It is reactive with adenoma type uterine carcinoma and normal mucosa of the uterine cervix and with normal surface epithelium of the oviduct. Among nongynecological tumors, OM-B antigen was present in metastatic tumors to the ovary as well as in gastric and pancreatic carcinomas, while OM-C was in metastatic tumors to the ovary and gastric and colonic carcinomas. Thus, the serological analysis showed that these three MoAbs showed selective specificities to mucinous and endometrioid types of ovarian tumors. Preliminary characterization of these three OM antigens suggested that these are distinct from carcinoembryonic antigen or ABH blood group-related antigens.
A case is reported here in which segmental autotransplantation of the pancreas was performed after total pancreatectomy for advanced periampullary carcinoma in an attempt to preserve pancreatic endocrine function. The postoperative course was uneventful. The requirement of insulin decreased after the operation and the daily profile examination, done 5 months following surgery, showed a permissive fluctuation of blood sugar levels without insulin injection. Thus, segmental autotransplantation of the pancreas offers a method of preserving pancreatic endocrine function after total pancreatectomy for periampullary carcinoma in selected patients.
To clarify interactions between carcinoma and mesenchymal cells, we examined the extracellular matrix-substance remaining on culture dishes after confluent growths of gastric carcinoma cells were removed with EDTA. The matrix synthesized by poorly differentiated adenocarcinoma cells (cell lines KATO-III and MKN-45) cultivated in serum-free medium has a fibroblast (cell line WI38)-attachment activity, which is not detected in the matrix synthesized by a well differentiated adenocarcinoma (cell line MKN-28). This activity was not observed in KATO-III-matrix extracted with 6 M urea, but could be detected in a 1% SDS extract from the remaining matrix on the culture dishes after 6 M urea extraction. The activity was abolished by treatment with pronase (16 micrograms/ml), trypsin (0.005%) or alkali, but was unaffected by collagenase (80 micrograms/ml, 4 h) or chondroitinase ABC (1 U ml, 1 h). It is conceivable that the fibroblast-attachment activity of the matrix produced by poorly differentiated adenocarcinoma cells is related to the proliferation of interstitial connective tissue in vivo.
The characteristics of so-called "embryoid body" appearing in gonadal germ cell tumors were studied histologically and immunohistochemically on serial sections of three cases (one ovary and two testes). The embryoid bodies were usually observed to be contiguous with immature or mature intestinal ducts, hepatic nests, or epidermal cell nests on serial sections, though they appeared to be isolated in one section. The "amniotic cavity"-like structure of embryoid body was continuous with intestinal duct, and rarely with squamous cell nests, while the "yolk sac" was continuous with hepatic tissue. In these immature or mature structures, differentiation was always found independently of "disc," and portions of "ectoderm" and "endoderm" remained less differentiated in comparison with others. These findings were in contrast with a normal embryo in which immature and/or mature structures are derived from the embryonic disc. The amniotic cavity connected frequently with yolk sac. From the present results, the embryoid body is not considered to be a real or teratomatous embryo, but only a product during a divergent differentiation into intestine and liver from the plastic epithelium, which seems to be derived from an embryonic gut.
Endodermal sinus tumor (EST) arising in the endometrium is an extremely rare malignant neoplasm. To the authors' knowledge, this is only the second report of an EST arising in this location. The tumor was exophytic, 2.4 cm in diameter, and was located in the fundus uteri. It had infiltrated the circumambient endometrium slightly. Preoperative serum alpha-fetoprotein (AFP) levels were markedly elevated, 1580 ng/ml. The patient received a simple abdominal hysterectomy and bilateral salpingo-oophorectomy followed by combination chemotherapy consisting of vincristine, actinomycin D, and cyclophosphamide. To date, there has been no evidence of tumor recurrence, and serum AFP titers, which had returned to normal 7 weeks after surgery, continue to remain within normal limits. We believe this is the first successful treatment of a documented case of primary EST of the endometrium.
Immunohistochemical localization of chondroitin sulphate and dermatan sulphate proteoglycans (PGs) was observed in 70 tumour tissues, using monoclonal antibodies 9A-2 and 3B-3 raised against core molecules obtained from chondroitin sulphate PG by chondroitinase ABC-treatment. They recognize a stub of delta Di-4S and delta Di-6S binding to core protein via a linkage tetrasaccharide, respectively. The antibody 6B6 raised against dermatan sulphate PG obtained from an ovarian fibroma capsule in our laboratory was also used. The interstitial fibrous elements, so-called 'specific stroma' within the cancer cell nests contained chondroitin 4-sulphate PG as revealed with 9A-2, whereas the surrounding connective tissue and the preexisting fibrous connective tissue involved in the tumour growth consisted of dermatan sulphate PG with a considerable amount of chondroitin 4-sulphate PG. Chondroitin 6-sulphate PG as revealed with 3B-3 was located in the connective tissue proliferating from blood vessels and muscle tissue in association with the invasive growth of tumour cells. Chondroitin 6-sulphate PG was also observed in the basement membrane components of some tumours. In non-epithelial tumours (fibrogenic, chondrogenic, osteogenic and neurogenic tumours), chondroitin 4-sulphate was in fibrous portions. When collagenization and hyalinization progressed, dermatan sulphate PG was observed to increase in quantity.
In order to clarify the biological characteristics of rat mammary tumors induced by 7,12-dimethylbenz-[a]-anthracene (DMBA), histochemical and immunohistochemical studies were performed. Two types of luminal spaces were observed within the tumor. In one type, the lumen was surrounded by eosinophilic columnar cells which were strongly reactive for soybean agglutinin (SBA) but weakly stained with keratin antibodies. In the luminal spaces, substances positive for PAS, dialyzed iron ferrocyanide or alcian blue and resistant to mucopolysaccharidase were occasionally observed. Ultrastructurally, the luminal surface was characterized by the presence of microvilli and tight junctions. In the other type, the lumen was often found in highly cellular foci and surrounded by pale, polygonal or elongated cells which were weakly stained with keratin antibodies but not SBA. The luminal spaces presented a peculiar structure filled mainly with mucoid substances sensitive to hyaluronidase, chondroitinase ABC and heparitinase, and the inner surface of the spaces was surrounded by basement membrane components: laminin, fibronectin and type IV collagen. The results of the present study therefore showed that DMBA-induced mammary tumor consists, partly, of a structure resembling human adenoid cystic carcinoma.
A 47-year-old woman was admitted complaining of irregular uterine bleeding. On surgery, an ovarian tumor was found together with a broad-based polypoid endometrial mass. These lesions were histologically diagnosed as granulosa cell tumor with invasive adenocarcinoma of the endometrium. To our knowledge, only four other cases of granulosa cell tumor with adenocarcinoma of the endometrium have been reported in Japan, although our case was unique in showing invasion to the uterine myometrium.
Mortality, major causes of moribundity, and spontaneous tumors in CD-1 mice were studied in 891 males and 890 females, which were used as controls in 11 different 2-year chronic and oncogenicity studies during the past 5 years. Average mortality of males and females at 83 weeks of age was 32.6% and 28.6%, respectively, and at 109 weeks of age was 66.4% and 63.3%, respectively. Mortality was significantly lowered in males and females born after 1980 in accordance with an abruptly decreased occurrence of systemic amyloidosis in these animals. The major cause of death or moribundity included systemic arteritis, systemic amyloidosis, auricular thrombosis, glomerulosclerosis, lymphoma, and pulmonary adenocarcinoma in both sexes. Dysuria and hepatocellular carcinoma in males and mammary adenocarcinoma in females were also critical lesions. The major tumors occurring at more than 3% incidence were systemic lymphoma, adenoma/adenocarcinoma of the lung, adenoma/carcinoma of the liver and adenoma/adenocarcinoma of the Harderian gland for males, and systemic lymphoma, adenoma/adenocarcinoma of the lung, adenoma/carcinoma of the liver, leiomyoma/leiomyosarcoma of the uterus, adenoma/adenocarcinoma of the pituitary (anterior), adenoma/adenocarcinoma of the mammary gland and adenoma/adenocarcinoma of the Harderian gland for females. Intralaboratory heterogeneities in the incidence were recorded as follows: systemic lymphoma in 1 of 11 control groups (1/11) and adenoma/adenocarcinoma in 1/11 for males, and systemic lymphoma in 3/11, adenoma/adenocarcinoma of the lung in 2/11, adenoma/adenocarcinoma of the liver in 1/11, and adenoma/adenocarcinoma in 1/11 for females.
We purified dermatan sulfate proteoglycan (PG) from the capsule of human ovarian fibroma for use as an immunogen. A monoclonal antibody, designated 6B6, was produced which reacts to the intact molecule of dermatan sulfate PG and the chondroitinase AC-treated core molecule on Western-blotted nitrocellulose membrane. Localization of materials showing crossreactivity to this antibody was studied in human tissues by indirect immunohistochemistry. The interstitial elements of almost all tissues examined were positive for the antibody: dermis, submucosal layer of digestive tract, perichondral layer, perivascular connective tissue, perineurium, adventitia of aorta, vessel wall of vein, pleura, and fibrous capsule of kidney and liver. Positive staining was also observed in fibrous elements at post-necrotic foci of cardiac muscle and pancreas, and at atherosclerotic lesions of aorta. The distribution of the antigen, core protein of the dermatan sulfate PG, revealed with 6B6 was compared to that of the dermatan sulfate side chain, which was demonstrated with antibody 9A-2 (Couchman et al.: Nature 307:650, 1984) after treatment with chondroitin sulfate B-lyase. The distribution of both antigens, core protein, and dermatan sulfate side chains showed the same pattern, with minor exceptions. The antibody 6B6 will be a useful tool to study the immunohistochemical localization of dermatan sulfate PG.
A retrospective study was made of 56 patients with squamous cell lung cancer, who were inoperable or unresectable and had completed a course of radiotherapy at Jichi Medical School Hospital from August, 1973 to December, 1986. All cases had a performance status score of 80-100 (Karnofsky), no evidence of a distant metastases and tumors that had received a minimum total dose of 50 Gy. The patients were treated with one of three therapy regimens: split course (SC, 32 Patients), conventional fractionation (CF, 13), or multiple daily fractionation (MDF, 11). The over-all median survival time was 13.0 months, and the 2 and 5-year survival rates were 29.2% and 14.7%, respectively. The patients treated with the split course had the lowest survival rate in comparison with the other two groups. Comparison of the patients with the continuous course (CF + MDF) were significantly higher (P less than 0.025) than that of the split course. Patients with MDF had better local control. Age, tumor stage, and the size of the booster field were found to be factors which influenced the survival rate with a fair statistical significance. The survival rate increased with an increase in age, a decrease in the tumor stage, and in the size of the booster field. These findings have important implications for the design of future clinical trials for patients with squamous cell lung cancer.