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Biomedical subjects

E Kobayashi

Publications and source records attributed to E Kobayashi.

At least 325 records · Page 18Linked to original sources

Combination effect of navelbine (vinorelbine ditartrate) with cisplatin against murine P388 leukemia and human lung carcinoma xenografts in mice.

The in vivo combination effect of navelbine (NVB, KW-2307) plus cisplatin was compared with that of vindesine (VDS) plus cisplatin in terms of antitumor activity and side effects. The antitumor activity of NVB or cisplatin against i.p. inoculated P388 leukemia was augmented by their combination on various schedules when the interval of administrations was within 24 h. Against i.v. inoculated P388 leukemia, the most significant combination effect was observed when cisplatin was administered 4 h after NVB injection (ILS(%) > 451) and three long-term survivors were observed. On this schedule, the combination of LD10 of each drug was achieved, indicating the lack of addition of toxicity. This was further proved by examination of body weight change, white blood cell count and platelet count. Interestingly, significant elevation of blood urea nitrogen concentration by cisplatin was prevented by the combination with NVB. The combination of maximum tolerated dose of NVB and cisplatin was also tolerable in nude mice, and their combination effect was observed against human lung large cell carcinoma Lu-65 and adenocarcinoma PC-12. The number of toxic death mice was more in VDS plus cisplatin-treated groups than in NVB plus cisplatin-treated groups, indicating that the combination chemotherapy of NVB plus cisplatin is a better regimen than that of VDS plus cisplatin in experimental tumor systems.

Animals↗

Identification, cDNA cloning, and gene expression of soluble starch synthase in rice (Oryza sativa L.) immature seeds.

Three forms of soluble starch synthase were resolved by anion-exchange chromatography of soluble extracts from immature rice (Oryza sativa L.) seeds, and each of these forms was further purified by affinity chromatograph. The 55-, 57-, and 57-kD proteins in the three preparations were identified as candidates for soluble starch synthase by western blot analysis using an antiserum against rice granule-bound starch synthase. It is interesting that the amino-terminal amino acid sequence was identical among the three proteins, except that the 55-kD protein lacked eight amino acids at the amino terminus. Thus, these three proteins are products of the same gene. The cDNA clones coding for this protein have been isolated from an immature rice seed library in lambda gt11 using synthetic oligonucleotides as probes. The deduced amino acid sequence of this protein contains a lysine-X-glycine-glycine consensus sequence for the ADP-glucose-binding site of starch and glycogen synthases. Therefore, we conclude that this protein corresponds to a form of soluble starch synthase in immature rice seeds. The precursor of the enzyme contains 626 amino acids, including a 113-residue transit peptide at the amino terminus. The mature form of soluble starch synthase shares a significant but low sequence identity with rice granule-bound starch synthase and Escherichia coli glycogen synthase. However, several regions, including the substrate-binding site, are highly conserved among these three enzymes. Blot hybridization analysis demonstrates that the gene encoding soluble starch synthase is a single-copy gene in the rice genome and is expressed in both leaves and immature seeds. These results suggest that soluble and granule-bound starch synthases play distinct roles in starch biosynthesis of plant.

Amino Acid Sequence↗

Comparison of K-ras oncogene activation in pancreatic duct carcinomas and cholangiocarcinomas induced in hamsters by N-nitrosobis(2-hydroxypropyl)amine.

The presence of K-ras point mutations in pancreatic duct carcinomas and cholangiocarcinomas induced by N-nitrosobis(2-hydroxypropyl)amine (BHP) in Syrian hamsters was investigated by single-strand conformation polymorphism analysis of polymerase chain reaction products from frozen fresh materials in order to clarify the K-ras mutation rates in those two carcinomas induced simultaneously by one carcinogen, BHP. In the examined pancreatic duct carcinomas, 10 out of 16 were positive for a mutation in codon 12 while 3 out of 12 cholangiocarcinomas demonstrated mutation of K-ras gene. G-to-A transition was detected in the second position of codon 12 in both pancreatic carcinomas and cholangiocarcinomas. These results suggest that the role of genetic alteration in carcinogenesis may differ with the target organ, even when initiation is with the same carcinogen.

Animals↗

K-ras gene mutation in early ductal lesions induced in a rapid production model for pancreatic carcinomas in Syrian hamsters.

The presence of K-ras gene mutation was examined in experimentally induced preneoplastic pancreatic ductal lesions. Syrian hamsters received 70 mg/kg of N-nitrosobis(2-oxopropyl)amine (BOP) followed by repeated exposure to an augmentation pressure regimen consisting of choline-deficient diet combined with DL-ethionine and L-methionine and administration of 20 mg/kg BOP. After two augmentation pressure cycles, pancreatic ductal cell hyperplasias appeared and after three cycles, atypical hyperplasias of pancreatic ductal cells and intraductal carcinomas developed. K-ras mutations were detected by single-strand conformation polymorphism analysis of polymerase chain reaction products and nucleotide sequencing. The results showed that K-ras mutation had occurred in one of 9 simple hyperplasias of pancreatic ductal epithelium, in 5 of 9 atypical hyperplasias, and in 4 of 8 intraductal carcinomas. The findings thus suggested that K-ras is activated in association with very early stage malignant transformation of pancreatic ductal cells in hamsters.

Animals↗

A novel renal cell carcinoma susceptibility gene maps on chromosome 10 in the Eker rat.

Hereditary renal cell carcinoma (RC) in the rat, originally reported by Eker in 1954, is an example of Mendelian dominant predisposition to a specific cancer in an experimental animal. We previously reported that this predisposing inherited gene is a tumor suppressor gene fitting Knudson's "two-hit" model. This study was designed to map the RC susceptibility gene in the Eker rat using backcross animals. Our present data clearly show that the RC gene is genetically linked to the protamine-1 gene (Lod score = 11.65) and the interleukin-3 gene (Lod score = 4.13), both of which are located on the proximal part of rat chromosome 10. Rat chromosome 10 is currently believed to have no syntenic relationship to human chromosome 3p, the presumed site of the putative tumor suppressor gene for human RC and the locus of von Hippel Lindau disease (affected patients develop multiple RCs). Thus, the Eker rat might have a mutation of a novel tumor suppressor gene related to renal carcinogenesis.

Animals↗

Comparison of potentiality to induce graft-versus-host reaction with small bowel, pancreas/spleen, and liver transplantation in the rat.

Although small bowel transplantation (SBT), or pancreas-spleen transplantation (PST) often lead to lethal graft-versus-host reaction (GVHR) in experimental animals, fatal GVHR is rare after clinical liver transplantation. This study describes a modified model of SBT and PST in the rat using cuff techniques applied to the renal artery and vein of the recipient. The ability of LEW (RT1(1)) or BN (RT1n) lymphocytes accompanying intestinal, splenic, or hepatic grafts to induce lethal GVHR in (LEW x BN) F1 hybrid recipients was compared. SBT and PST experiments showed that lethal GVHR always occurred in LEW-into-F1 combination, but was much less frequent in BN-into-F1 SBT. In mixed lymphocyte reaction (MLR), LEW mesenteric or splenic T cells showed significantly higher proliferative responses against BN stimulators than did BN mesenteric or splenic T cells against LEW. Adoptive cell transfer experiments using mesenteric or splenic cells also showed that LEW cells were higher responders than BN. In contrast with SBT and PST results, a lethal GVHR was not induced after liver or pancreas grafting alone in either parent-to-F1 combination. In MLR, hepatic T cells from either parent failed to elicit a proliferative response against allostimulators. These results indicate that the occurrence of lethal GVHR is dependent upon the reactivity of parental lymphocytes against allo-antigenicity of F1 hybrids and also upon the lymphoid tissue transplanted. The lack of alloreactivity of hepatic T cells accounts for the absence of lethal GVHR after liver grafting.

Animals↗

Study on the castability of Co-Cr alloy for cast plates. Part 3: Effects of alloy fusion temperature and the heating temperature of the cast ring.

Co-Cr alloy is used more frequently than Ni-Cr alloy as a non-precious alloy for cast plates in Japan. However, since the melting temperature of Co-Cr alloy is very high, about 1300 degrees C, and since it oxidizes easily, a vacuum-pressure casting machine capable of melting this alloy in a reduced atmosphere has recently been developed. Using this machine, the effects of fusion temperature and the heating temperature of the cast ring on the Co-Cr alloy were studied. It was found that in the vacuum-pressure casting method, both the fusion temperature of the Co-Cr alloy and the heating temperature of the cast ring had a significant effect (p < 0.01) on the castability of the Co-Cr alloy.

Chromium Alloys↗

[Study of uneven pulmonary ventilation by sequential bolus method].

We report a new method of measuring the sequential ventilation associated with the primary mechanism for ventilation inhomogeneity. Four types of sequential curves were examined using simultaneous washouts of multiple tracer boluses inhaled from residual volume (RV) and at volumes above RV. The factors that affected the classification of curves were analyzed by the theory of quantification from the statistical data of blood gases, lung function tests, X-ray and clinical diagnosis. This method was applied to evaluate the ventilation distribution in 100 patients with pulmonary disease. It provided clinical information on certain types of disease which cannot be detected by traditional lung function tests. Sequential bolus method may permit determination of whether the disease has predominantly intra or inter-regional inhomogeneity.

Evaluation Studies as Topic↗

Influence of mold materials and heat treatment on tensile properties of Ni-Ti alloy castings.

The influence of mold materials and heat treatment on the tensile properties and the transformation temperatures of Ni-Ti alloy castings was investigated by tensile test and differential scanning calorimetry (DSC) in order to apply the special properties of the alloy to dental field. The compositions of the two alloys examined were 49.0 and 49.2 at % Ti. A silica investment and a magnesia investment were used as the mold materials. Heat treatment at 440 degrees C for 1.8 ks was performed. Apparent proof strength decreased in both compositions, and residual strain increased in Ni-49.2Ti by the heat treatment. Elongation increased in Ni-49.0Ti with use of the magnesia mold or by the heat treatment. The transformation temperatures of Ni-49.2Ti increased with use of the magnesia mold. The change by the heat treatment suggested a structural change. The development of a suitable method for the casting of the alloy is expected to bring about the development of new devices and therapy in dentistry.

Calorimetry, Differential Scanning↗

[Antitumor activity of navelbine (vinorelbine ditartrate), a new vinca alkaloid analog].

The antitumor activity of navelbine (vinorelbine ditartrate, KW-2307) against murine and human transplantable tumors was compared with those of other vinca alkaloids, vindesine (VDS), vincristine (VCR) or vinblastine (VLB). KW-2307 and VDS increased the life span of mice bearing ascitic tumors (P 388 leukemia, L 1210 leukemia, EL-4 lymphoma, Colon 26, FM 3 A mammary carcinoma and M 5076 sarcoma) slightly more than VCR or VLB. A significant difference was not found in the antitumor activities against 6 murine solid tumors (B 16 melanoma, Colon 26, FM 3 A mammary carcinoma, Lewis lung carcinoma, M 5076 sarcoma and Sarcoma 180). However, a remarkable difference was observed in the antitumor activities against 11 human tumors inoculated into nude mice. The activity of KW-2307 was more than those of other 3 drugs against 4 human non-small cell lung carcinomas (Lu-65, Lu-99, LC-6 and L-27) and 2 stomach carcinomas (St-4 and St-40). KW-2307 and VDS were also effective in inhibiting the growth of 2 human breast carcinomas (MX-1 and Br-10).

Animals↗

Localization and health effects of lanthanum chloride instilled intratracheally into rats.

Lanthanum (La) is one of the rare earths used in diverse high technology fields for which sufficient data for assessing its health effects have been lacking. The biological effects and metabolic behaviors of La were studied by instilling lanthanum chloride intratracheally into male Wistar rats. The distribution of La among tissues revealed that the metal remains mostly in the lung with a biological half-time of 244 days. The subcellular localization by transmission electron microscopy with an X-ray microanalyzer indicated that La localizes in macrophages as high electron-dense granular inclusions in lysosomes and on the cell surface and basement membranes of type I pneumocytes among lung cells. The pulmonary health effects were examined by biological indices of the bronchoalveolar lavage fluid (BALF) and lung tissue. The acute toxicity estimated by lactate dehydrogenase activity in BALF was comparable to those of yttrium and copper that had been determined under the same protocol. Microscopic examination of the lung indicated a characteristic increase in the number of eosinophils.

Animals↗

Mechanism of the rejection of major histocompatibility complex class I-disparate murine skin grafts: rejection can be mediated by CD4+ cells activated by allo-class I + II antigen in CD8+ cell-depleted hosts.

In the preceding article, we analyzed the immunohistochemical rejection mechanism of major histocompatibility complex (MHC) class I (H-2K)-disparate murine skin grafts, and showed that only CD8+ cells infiltrated at the site of the epithelial tissue of MHC class I-disparate graft. We also showed that perfect survival of MHC class I-disparate grafts were attained in thymectomized recipients treated with anti-Lyt-2 monoclonal antibody. In this report, we showed that these long-surviving allo-class I grafts were rejected in the absence of CD8+ cells by stimulation with allo-MHC class I + II-disparate graft as the second stimulation. Furthermore, it was immunohistochemically revealed that under that condition, a large number of CD4+ cells infiltrated into the epithelial tissue of these long-surviving class I grafts, which were going to be rejected 2-5 d after the transplantation of a second graft with MHC class I + II difference. This result directly shows that CD4+ cells are able to became effectors for the rejection of allo-MHC class I (H-2K) skin graft.

Animals↗

Polymorphic microsatellite loci of the rat (Rattus norvegicus).

The EMBL and GenBank DNA databases were searched for microsatellite sequences of the rat containing dinucleotide repeats of (CA)n and (GA)n. Among those obtained, 23 sequences were analyzed by polymerase chain reaction to examine the size variation of the amplified fragment in inbred rat strains. All of the 23 microsatellite sequences varied in size among the strains tested. The 23 microsatellite loci in a pair of substrains separated from the same progenitor strain were then analyzed. Fragments identical in size were observed in all loci of the two substrains, indicating the stability of the microsatellite over a large number of generations. The microsatellite loci, therefore, should be useful markers for linkage analyses in the rat.

Animals↗