Search PubMed⌕ Search

Biomedical subjects

T Yano

Publications and source records attributed to T Yano.

At least 289 records · Page 16Linked to original sources

The inhibitory effect of vitamin E on K-ras mutation at an early stage of lung carcinogenesis in mice.

In this study, we investigated the effect of vitamin E on the activation of the K-ras oncogene with a 61st codon A-->T mutation at an early stage of urethane-induced lung carcinogenesis in mice. Thirty days after urethane injection, the K-ras mutation was detected in 64% of lung samples tested by mutant-allele-specific amplification. The consumption of a supplemented diet with about 20-times more vitamin E than the control diet, only during the promotion phase or during both the initiation and promotion phases of lung carcinogenesis, reduced the frequency of the mutation to 36 and 18%, respectively. Also, vitamin E suppressed the level of proliferating cell nuclear antigen as a marker of cell proliferation in the lungs of mice treated with urethane. These results support the notion that vitamin E is a useful chemopreventive agent against lung cancer.

Animals↗

The proton-translocating NADH-quinone oxidoreductase (NDH-1) of thermophilic bacterium Thermus thermophilus HB-8. Complete DNA sequence of the gene cluster and thermostable properties of the expressed NQO2 subunit.

The genes encoding the proton-translocating NADH-quinone oxidoreductase (NDH-1) of a thermophilic bacterium Thermus thermophilus HB-8 were cloned and sequenced. They constitute a cluster that is composed of 14 structural genes and contains no unidentified reading frames. All of the 14 structural genes, which are designated NQO1-14, encode subunits homologous to those of Paracoccus denitrificans NDH-1, respectively, and are arranged in the same order as other bacterial NDH-1 genes. T. thermophilus NDH-1 contains at most nine putative iron-sulfur cluster binding sites, eight of which are commonly found in other organisms. The T. thermophilus NQO2 subunit was expressed in Escherichia coli. The expressed subunit bears a single [2Fe-2S] cluster whose optical and EPR properties are very similar to those of N1a cluster in the P. denitrificans NQO2 subunit (Yano, T., Sled', V.D., Ohnishi, T., and Yagi, T. (1994) Biochemistry 33, 494-499). These results strongly suggest that the T. thermophilus NDH-1 is similar to other NDH-1 enzyme complexes in terms of subunit and cofactor composition. The T. thermophilus NQO2 subunit displayed much higher stability than the mesophilic equivalent and its iron-sulfur cluster remained intact even after incubation for 3 h at 65 degrees C under anaerobic conditions. With the advantage of thermostability, the T. thermophilus NDH-1 provides a great model system to investigate the structure-function relationship of the NDH-1 enzyme complexes.

Amino Acid Sequence↗

Comparison of the surgical results of lobectomy with bronchoplasty and pneumonectomy for lung cancer.

BACKGROUND: We retrospectively compared sleeve lobectomy (SL) and pneumonectomy (PN) for lung cancer in terms of surgical complications and postoperative disease-free survival, as well as incidence and pattern of recurrent disease. METHODS: From 1977 to 1993. 29 patients with primary lung cancer underwent sleeve resection at our institution. The pneumonectomy group consisted of 29 cases that had been selected during the same period according to the following criteria: (1) in a tumor located in the upper lobe, there was no invasion within 1 cm from both the carina and the orifice of the middle and the lower lobe bronchus, whereas in a tumor located in the middle or lower lobe, there was no invasion within 1 cm of the orifice of the upper bronchus, (2) there was no invasion to the trunks of the pulmonary vessels, (3) there was no invasion to any other lobes, (4) a complete resection was achieved. RESULTS: No differences were observed between the two groups regarding stage, histological population, or age. The incidence of postoperative complications was 13.7% in the SL group (2 cases each of pneumonia and arrythmia), and 24.1% in the PN group (3 bronchopulmonary fistula, 2 bleeding, 1 instance each of arrythmia and acute cardiac failure, and 2 operation-related deaths) (P < 0.05). The 3-year disease-free survival was 65.7% in SL, 58.8% in PN (no statistical significance in the log-rank test). Recurrent disease was observed in the local regions of three patients in the SL group and six patients in the PN group, and at distant organs of six patients in the SL group and seven in the PN group. CONCLUSIONS: These findings thus suggest that as a curative treatment, lobectomy with bronchoplasty may be a safer procedure than pneumonectomy for lung cancer.

Adult↗

Intraoperative intrapleural hypotonic cisplatin treatment for carcinomatous pleuritis.

BACKGROUND AND OBJECTIVES: We recently developed a new intraoperative intrapleural hypotonic cisplatin treatment for carcinomatous pleuritis found at thoracotomy in non-small cell lung cancer patients. In the present study, the efficacy and adverse events of this treatment as well as the pharmacokinetics of cisplatin in the blood after the treatment were evaluated. PATIENTS AND METHODS: Twenty-one patients received the treatment for 15 minutes after completing the intrathoracic surgical procedures. The total and free platinum levels in the blood of five patients were then measured. As a control, 29 patients without such treatment were reviewed retrospectively. RESULTS: The survival rates in the treatment and non-treatment groups were similar. The pleural disease free survival of the treated patients was, however, significantly higher than that of the non-treated patients. Such pleural disease as effusion and the growth of the pleural disseminated tumors only appeared in three of the 21 (14%) treated patients while 26 of 29 (90%) non-treated patients had clinically detected pleural disease. The blood platinum levels after the treatment were extremely low and such low levels probably induced no systemic adverse events after the treatment. The only adverse event of this treatment was an increase in the postoperative drainage volume. CONCLUSIONS: These observations seem to suggest that intraoperative intrapleural hypotonic cisplatin treatment for carcinomatous pleuritis found at thoracotomy can, at least, delay the appearance of the pleural disease without any adverse events.

Adult↗

A C57BL/KsJ mouse model of Niemann-Pick disease (spm) belongs to the same complementation group as the major childhood type of Niemann-Pick disease type C.

A cell line (SPM-3T3) derived from a C57BL/KsJ mouse model of Niemann-Pick disease type C (NP-C) shows biochemical abnormalities similar to those in fibroblasts derived from NP-C. Somatic cell hybridization analysis of the SPM-3T3 cells and five fibroblast strains derived from NP-C patients (four childhood cases and one adult case) was carried out. The criterion for complementation was the restoration of a normal intracellular fluorescent pattern in multinucleated cells stained with filipin to demonstrate cholesterol accumulation. These cells can be assigned to two complementation groups. The SPM-3T3 cells did not complement cell strains derived from childhood-type NP-C, while they complemented a cell strain derived from an adult patient. Our results suggest that SPM-3T3 represents a genetically authentic model of a major complementation group of NP-C, and that NP-C consists of genetically heterogeneous groups.

3T3 Cells↗

Diagnosis of visceral pleural invasion in resected lung cancer using a jet stream of saline solution.

BACKGROUND: Visceral pleural invasion by the tumor is an important prognostic factor in patients undergoing resection for lung cancer. We developed a method to detect more accurately the presence of visceral pleural invasion in resected lung cancer. METHODS: The surface of the visceral pleura over 90 resected peripheral tumors was irrigated twice with a jet stream of saline solution using a 20-mL syringe with a 21-gauge needle, and then the fluid, which contained desquamated cells, was collected for cytologic analysis. When cancer cells were found in the collected fluid, the tumor was judged to have invaded the visceral pleura. RESULTS: Thirty-eight (42%) resected tumors were identified as having visceral pleural invasion either by our new method or by pathologic examination. Twenty-four cases were detected by the jet stream of saline method alone, 5 by pathologic examination alone, and 9 by both techniques. The sensitivity and accuracy of the two approaches in the diagnosis of visceral pleural invasion were 87% and 94%, respectively, for our new method, and 37% and 73%, respectively, for pathologic examination (p < 0.0001). Furthermore, among 38 patients who had a tumor demonstrating visceral pleural invasion, 5 (13%) and 9 (24%) patients, respectively, had cancer cells in the pleural effusion and intrapleural lavage fluid. CONCLUSIONS: Our findings suggest that our method is useful in detecting cancer invasion of the visceral pleura, which is considered one of the causes of malignant effusion.

Adenocarcinoma↗

Beta-very low density lipoprotein induces triglyceride accumulation through receptor mediated endocytotic pathway in 3T3-L1 adipocytes.

To elucidate the mechanism of triglyceride (TG) accumulation in adipocytes induced by TG-rich lipoproteins, we examined the effect of beta-very low density lipoprotein (beta-VLDL) on TG accumulation in 3T3-L1 adipocytes. Beta-VLDL did not induce TG accumulation in 3T3-L1 preadipocytes but in 3T3-L1 adipocytes. TG accumulation was significantly inhibited by cytochalasin B, an inhibitor of receptor mediated endocytosis. In contrast, cytochalasin B did not inhibit free fatty acid induced TG accumulation in adipocytes. The binding of [125I]beta-VLDL to preadipocytes was inhibited completely by both beta-VLDL and LDL. In sharp contrast, the binding of [125I]beta-VLDL to adipocytes was inhibited completely by beta-VLDL, but partially by LDL. The VLDL receptor mRNA was only expressed in adipocytes. These results suggest that beta-VLDL induced TG accumulation in adipocytes may be mediated through the VLDL receptor pathway.

3T3 Cells↗

Human beta-migrating very low density lipoprotein induces foam cell formation in human mesangial cells.

To elucidate the mechanism of foam cell formation in the mesangial region of a kidney observed in a familial type III hyperlipoproteinemic patient presenting with diabetes mellitus and nephrotic syndrome, we have examined, in the present study, the effect of human beta-VLDL (apo E2/E2) on foam cell formation in human mesangial cells, since an increase in beta-VLDL is a characteristic feature of this patient. Human beta-VLDL (apo E2/E2) induced foam cell formation in human mesangial cells. The binding of [125I]LDL to human mesangial cells was inhibited completely by both LDL and beta-VLDL. On the other hand, the binding of [125I]beta-VLDL was completely inhibited by beta-VLDL, but partially by LDL. The LDL receptor, but not the VLDL receptor was down-regulated by accumulation of cholesteryl esters. These results suggest that human beta-VLDL (apo E2/E2)-induced foam cell formation in mesangial cells is mediated through both the LDL receptor pathway and the beta-VLDL specific pathway, in which the VLDL receptor is one of the candidates.

Blotting, Northern↗

Effects of ethyl-all-cis-5,8,11,14,17-icosapentaenoate (EPA-E), pravastatin and their combination on serum lipids and intimal thickening of cuff-sheathed carotid artery in rabbits.

The anti-arteriosclerotic effects of ethyl all-cis-5, 8, 11, 14, 17-icosapentaenoate (EPA-E), pravastatin and their combination in cuff-treated rabbits were investigated. EPA-E at 600 mg/kg, pravastatin at 50 mg/kg or their combination was orally administered once daily for 5 weeks, and each of the animals was sheathed with a cuff on the carotid artery 2 weeks after the beginning of drug administration. EPA-E, pravastatin and their combination significantly reduced serum total cholesterol compared to the control group. EPA-E also potently reduced serum triglyceride, while pravastatin only slightly reduced it. The combination of these two agents had the most potent effect on the level of serum triglyceride. Serum phospholipids were also reduced by these treatments in a similar fashion. At the end of treatment, diffuse intimal thickening was observed in the cuff-covered region in all animals in the control group, and the intima/media area ratio in this group was 0.293 +/- 0.038. Treatment with EPA-E alone tended to prevent the intimal thickening, and the intima/media area ratio was 0.209 +/- 0.058 (p = 0.094). This ratio was 0.287 +/- 0.048 (p = 0.902) when pravastatin was administered alone, indicating that it had no significant effect on intimal thickening. The ratio was 0.175 +/- 0.041 (p = 0.042) when both EPA-E and pravastatin were administered, indicating that this combination had a significant inhibitory effect on intimal thickening in the cuff-sheathed region. These findings suggest that combined treatment with EPA-E and pravastatin is more effective than respective monotherapies in lowering serum lipids and/or preventing an intimal thickening as events of atherogenesis.

Animals↗

Measurement of spinal cord blood flow by an inhalation method and intraarterial injection of hydrogen gas.

PURPOSE: This study was performed to determine spinal cord blood flow using the H2 clearance method. METHODS: In 12 dogs we measured blood flow determined by hydrogen clearance techniques (BF) in both gray and white matter by spinal cord puncture, and compared the results with BF measured by a catheter inserted intrathecally to avoid spinal cord injury. We studied direct intraarterial and intravenous injection of hydrogen in addition to the inhalation method because hydrogen is an explosive gas. RESULTS: BF measured intrathecally with catheters adherent to either the ventral or the dorsal funiculus did not differ significantly from that of the gray matter. BF measured with a catheter inserted into the epidural space was about one fourth of the BF measured intrathecally. Values measured by the intraarterial injection method did not differ significantly from those obtained by the inhalation method. CONCLUSIONS: BF measured with a catheter inserted intrathecally reflects blood flow in the gray matter of the spinal cord. Using intraarterial injection of H2, BF was safety and accurately measured while avoiding the risk of explosion.

Administration, Inhalation↗

G-CSF-induced mobilization of peripheral blood stem cells for allografting: comparative study of daily single versus divided dose of G-CSF.

We conducted a comparative study on a daily single versus a divided dose of G-CSF for G-CSF-induced mobilization of peripheral blood stem cells (PBSC) in eleven HLA-identical sibling donors of allogeneic PBSC transplantation (PBSCT). Six donors received double subcutaneous injections of G-CSF at a dose of 5 micrograms/kg x 2/day for 5 days (Group A), while the remaining five received single subcutaneous injection at a dose of 10 micrograms/kg/day for 5 days (Group B). The numbers of circulating CD34+ cells, myeloid progenitors (CFU-GM) and erythroid progenitors (BFU-E) reached peak values at day 5 of G-CSF administration in both groups. The mean number of CD34+ cells harvested per apheresis was 4.4 x 10(6)/kg (cells/body weight of each donor, range: 0.8-7.9 x 10(6)/kg) in Group A and 5.1 x 10(6)/kg (range: 3.0-9.0 x 10(6)/kg) in Group B. There were no significant differences between these two groups in total numbers of CFU-GM, BFU-E, or T-lymphocytes harvested. Adverse effects including mild to moderate bone pain and thrombocytopenia were transient and well tolerated. No difference was observed in the incidence of adverse effects between the two groups. These observations suggest that there is no difference in G-CSF-induced mobilization of PBSC between daily single and divided dose of G-CSF to collect a sufficient number of PBSC for engraftment after allo-PBSCT.

Adolescent↗

The current status of postoperative complications and risk factors after a pulmonary resection for primary lung cancer. A multivariate analysis.

OBJECTIVE: The purpose of the present study is to identify the current postoperative complications after a pulmonary resection for primary lung cancer and the associated risk factors. METHODS: From 1988 to 1992, 291 patients with primary lung cancer, excluding T4 diseases, consecutively underwent a pulmonary resection at our institute. The observed postoperative complications were divided into non-life-threatening ones (simple arrhythmia, atelectasis, liver dysfunction, etc.) and life-threatening ones (respiratory failure, pyothorax, pneumonia, bronchopleural fistula, cardiac failure, cerebral infarction, myocardial infarction, etc.). Using logistic regression procedures, both univariate and multivariate analyses of the association between various perioperative factors and the incidence of postoperative complications were performed. RESULTS: Non-life-threatening complications occurred in 60 patients (20.6%) while life-threatening ones occurred in 36 (12.4%), and resulted in five in-hospital deaths (1.75%). Multivariate analyses showed that an age of 70 or older, a combined resection, an abnormality on preoperative ECG, and diffusing capacity of carbon monoxide (%DLco) below 70 were all independently associated with an increased non-life-threatening morbidity. On the other hand, an age of 70 or older, the need for a pneumonectomy, and a %DLco below 70 were also independently predominant risk factors for life-threatening morbidity. CONCLUSION: The risk factors for life-threatening morbidity therefore did not completely correspond to those for non-life-threatening morbidity. Since the mortality was quite low, even risk factors for life-threatening morbidity were not solely considered to be a contraindication for a major pulmonary resection.

Adult↗

Failure in resection of multiple pulmonary metastases from colorectal cancer.

BACKGROUND: To clarify whether or not multiple pulmonary metastases from colorectal cancer are contraindicated for a surgical resection, we retrospectively evaluated the influence of the number of pulmonary metastases on both the postthoracotomy survival and the pattern of the first failure. METHODS: From 1981 to 1993, 36 patients underwent a complete resection for pulmonary metastases from colorectal cancer. RESULTS: Of the various factors investigated including gender, primary site, disease-free interval, tumor size, the number of metastases, type of resection, and the history of hepatic metastases, only the number of pulmonary metastases was found to be significantly related to postthoracotomy survival. The rate of disease-free survival at 5 years was 62% for solitary metastasis (n = 17), 35% for two metastases (n = 8), and 0% for four or more metastases (n = 11). The pattern of failure also differed according to the number of pulmonary metastases. In particular, the incidence of local recurrence at the primary site increased with the number of pulmonary metastases (ie, 1 of 17 patients with a solitary metastasis, 3 of 8 with two metastases, and 6 of 11 with four or more metastases). CONCLUSIONS: These results suggest that multiple metastases might indicate the presence of local recurrence at the primary site; therefore, in cases of multiple pulmonary metastases, the primary site should be thoroughly explored.

Colorectal Neoplasms↗

The effects of a simplified method for cryopreservation and thawing procedures on peripheral blood stem cells.

A simplified method for cryopreservation at -80 degrees C of peripheral blood stem cells (PBSC) has been increasingly used for autologous PBSC transplantation in Japan. Although this method, using 6% hydroxyethyl starch (HES) and 5% dimethyl sulfoxide (DMSO) as a cryoprotectant without rate-controlled freezing, has several advantages over the conventional method using 10% DMSO with rate-controlled freezing, little is known about effects of long-term cryopreservation for years and thawing process on hematopoietic progenitors. We examined the recovery rates of BFU-E and CFU-GM in sample tubes cryopreserved by the simplified method under various conditions as follows: (1) long-term storage for 1-5 years; (2) DMSO exposure for 1 h after rapid thawing; and (3) thawing at a lower temperature other than 37 degrees C. In our study, we found that the recovery rates of BFU-E and CFU-GM were not affected by the length of cryopreservation period; they remained at more than 70% on average for 16-61 months. In our hands, a 1-h exposure to DMSO after rapid thawing was not toxic for hematopoietic progenitors. Furthermore, there was no significant difference in the recovery rates of BFU-E and CFU-GM between thawing at 37 degrees C and 20 degrees C. These observations indicate that PBSC cryopreserved for at least 5 years by the simplified method can be used clinically without losing hematopoietic activity, and suggest that hematopoietic activity of the thawed PBSC may be unaffected when PBSC are infused slowly within 60 min or even when PBSC are thawed gradually at room temperature.

Blood Preservation↗

Step vs. progressive exercise: the kinetics of phosphocreatine hydrolysis in human muscle.

It is well known that the VO2 readjustment rate of the whole body is faster when carrying out a given constant work load starting from a baseline of moderate exercise than from rest. However, it has not been established whether the above change is the result of faster kinetics of the oxidative machinery or, alternatively, the consequence of a reduced involvement of confounding factors such as anaerobic glycolysis or tissue O2 stores. The problem, earlier approached by chemical methods, was studied in man by 31P-NMRS assessment of the kinetics of phosphocreatine (PC) hydrolysis at the muscle level which is known to reflect the readjustment rate of the oxidative reactions. Twelve normal subjects carried out in a 90 cm bore modified Picker (1.5 T) magnet, a series of contractions by the plantar flexors reaching pre-set submaximal loads either in single steps (constant load, CL) or progressively (incremental exercise. I). If preceding exercise (I), compared to rest, influenced the rate of oxidations, the PC concentration at the target loads would be different for the two exercise modes, reflecting different energy deficits. This was not the case. Thus the present results show that the rate of readjustment of oxidations at the muscle level is not affected by priming exercise confirming previous findings and showing that theoretical models of VO2 control are experimentally applicable to man.

Adult↗

Common clonal origin of lymphocytes and plasma cells in splenic lymphoma with villous lymphocytes.

In two-thirds of patients with splenic lymphoma with villous lymphocytes (SLVL) a small amount of M-protein can be detected in association with the presence of plasma cells in the peripheral blood (PB) and/or bone marrow (BM). However, it is not known whether lymphoma cells and plasma cells originate from the same clone. In this report we describe a case of SLVL which was characterized by the presence of marked monoclonal gammopathy (IgG-kappa 90 g/l) and increased plasma cells in the BM. In an attempt to elucidate the origin of lymphoma cells and plasma cells, we performed morphological, cytogenetic and molecular studies on PB mononuclear cells (PBMNC) without plasma cells and BMMNC containing 10% plasma cells from this patient. Immunofluorescence showed that lymphoma cells and plasma cells were positive for cytoplasmic gamma heavy and kappa light chains. Well-developed endoplasmic reticulum was observed in the cytoplasmic organelles of PBMNC using an electron microscope. The mean IgG concentration in the 3 d supernatant cultures of PBMNC was 374 +/- 24 microg/l. More than 50% PBMNC differentiated into plasmacytoid cells in 6 d of liquid culture with IL-3 and IL-6. Analysis by two-colour FISH revealed that karyotypic abnormalities of monosomy X and trisomy 17 existed simultaneously in both lymphoma cells and plasma cells. JH gene rearranged bands from PBMNC and BMMNC by Southern blot hybridization were identical, whereas DNAs from PBMNC failed to hybridize with the Cmu probe. These observations strongly suggest that lymphoma cells and plasma cells originate from the same clone, and that plasma cells, as well as lymphoma cells, which have undergone class switch recombination, could produce IgG type M-protein in this case.

Aged↗