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Biomedical subjects

S Kudoh

Publications and source records attributed to S Kudoh.

At least 163 records · Page 9Linked to original sources
PubMed1997

CODE chemotherapy with and without granulocyte colony-stimulating factor in small-cell lung cancer.

Sixty-three patients with extensive-stage small-cell lung cancer were randomized to receive either cyclophosphamide, vincristine, doxorubicin and etoposide (CODE) alone or CODE plus recombinant human granulocyte colony-stimulating factor (rhG-CSF). rhG-CSF administration in support of CODE chemotherapy resulted in increased mean total received dose intensity for all drugs (P = 0.03) with a significant improvement in survival (P = 0.004).

Adult↗
PubMed1997

Defective granzyme B gene expression and lytic response in T lymphocytes infiltrating human renal cell carcinoma.

Granzyme B is a protein thought to play a pivotal role in the cytolytic functions of T cells. In view of this, the inducibility of this gene in freshly isolated T cells (T-TILs) infiltrating human renal cell carcinoma (RCC) in vitro was examined by using the reverse transcriptase-polymerase chain reaction (RT-PCR). A reduction in granzyme B messenger RNA (mRNA) expression in stimulated T-TILs from five of nine patients with RCC compared with autologous peripheral blood T cells was noted. The reduced expression was observed after multiple stimuli including anti-CD3 antibody, interleukin-2 (IL-2), and phytohemagglutinin (PHA). Because CD8+ T cells represent the predominant cytotoxic population, the ability of this cell population to express granzyme B mRNA after stimulation also was examined. When compared with CD8+ peripheral blood lymphocytes (T-PBLs) from patients with RCC and normal donors, the induction of granzyme B mRNA was reduced in CD8+ T-TILs. CD8+ T-TILs also had lower non-major histocompatibility complex (MHC)-restricted cytotoxic activity than did CD8+ T-PBLs against both Daudi cells and allogeneic RCC cell lines. These results show that in a subset of patients with RCC, depressed lytic activity of CD8+ TILs compared with CD8+ PBLs is present. Reduced granzyme B mRNA expression also was noted in selected patients.

Carcinoma, Renal Cell↗
PubMed1997

Enhancement of tumor radio-response by irinotecan in human lung tumor xenografts.

We investigated the ability of 7-ethyl-10-[4-(1-piperidino)-1-piperidino] carbonyloxycamptothecin (CPT-11) to increase tumor radio-response in vivo using human lung tumor xenografts. The xenografts were treated with (1) CPT-11 (10 mg/kg) intraperitoneally on days 1, 5 and 9, (2) single dose radiation (10 Gy/leg) on day 1, or (3) a combination regimen of both treatments in which radiation was given 1 h after the first dose of CPT-11. DNA flow cytometry studies were performed to define the cell cycle changes following treatment for 1 to 12 h with 0, 0.5, 2.0 or 8.0 ng/ml SN-38, the major active metabolite of CPT-11. In both small cell lung cancer (MS-1) and small cell/large cell carcinoma (LX-1) xenografts, combination treatment resulted in significant tumor regression compared with the use of CPT-11 (P = 0.0005, 0.0053) or radiation treatment (P = 0.00221, 0.0035) alone. Neither severe body weight loss nor enhanced skin reaction was observed following the combined treatment. In flow cytometry studies, the proportion of cells in G2/M-phase, the most radio-sensitive phase, increased after 1 h exposure to the lowest dose of SN-38 (0.5 ng/ml). These findings suggest that CPT-11 is a potent radiosensitizing agent, and that its activity is related to the cell cycle. This is the first report to indicate that CPT-11 serves as a radiosensitizer in vivo.

Animals↗
PubMed1997

PAMP is a novel inhibitor of the tachykinin release in the airway of guinea pigs.

Proadrenomedullin NH2-terminal 20 peptide (PAMP), a newly identified hypotensive peptide, may play physiological roles in airway and cardiovascular controls. This study was designed to determine the mechanism responsible for the bronchoprotective effects of PAMP on capsaicin-induced bron-choconstriction in anesthetized guinea pigs. PAMP (10(-8)-10(-6) M) significantly inhibited capsaicin-induced bronchoconstriction in a dose-dependent manner. The bronchoprotective effect of PAMP (10(-6) M) was as large as that of isoproterenol (10(-7) M) and lasted > 10 min. The concentration of immunoreactive substance P (SP) in bronchoalveolar lavage fluid after administration of capsaicin (4 x 10(-6) M) was 120 +/- 10 fmol/ml. PAMP significantly inhibited the release of immunoreactive SP in a dose-dependent manner (60 +/- 6 fmol/ml for (10(-6) M PAMP, P < 0.01; 84 +/- 6 fmol/ml for 10(-7) M PAMP, P < 0.01; and 95 +/- 6 fmol/ml for 10(-8) M PAMP, P < 0.05). PAMP (10(-6) M) did not significantly affect exogenous neurokinin A (NKA) or NKA + SP-induced bronchoconstriction, whereas isoproterenol (10(-7) M) significantly inhibited exogenous tachykinin-induced bronchoconstriction. These findings suggest that the bronchoprotective effects of PAMP are mainly due to inhibition of the release of tachykinins at airway C-fiber endings.

Adrenomedullin↗
PubMed1997

Adenosine modulates endothelin-induced bronchoconstriction in guinea pig airway.

The present study was designed to determine whether endogenous and exogenous adenosine modulates endothelin (ET)-induced bronchoconstriction. Exogenous adenosine enhances ET-induced bronchoconstriction. Following pretreatment with adenosine deaminase and theophylline to eliminate or antagonize endogenous adenosine, ET-1-induced bronchoconstriction was significantly attenuated, but not that of ET-3. In conclusion, this is the first report of an enhancement of ET-induced bronchoconstriction of guinea pig airways by endogenous and exogenous adenosine. Our findings may be useful in designing specific adenosine receptor antagonists as therapeutic agents in the management of bronchial asthma.

Acetylcholine↗
PubMed1997

Are BCG effects against urinary bladder carcinoma cell line T24 correlated with apoptosis in vitro?

Because we hypothesized that cell death when bacillus Calmette-Guérin (BCG) was instillated was correlated with apoptosis, cultured urinary bladder carcinoma cells were treated with BCG and examined whether they showed cell death due to apoptosis. Although the proliferative activity of T24 cells was suppressed, we could not recognize apoptosis clearly. Cell cycle analysis indicated an increased number of apoptotic cells, but no DNA degeneration was seen when DNA electrophoresis was applied, and few apoptotic cells were detected by an in situ apoptosis detection kit. As a result, cell death of T24 cells when BCG was applied may have other mechanisms except apoptosis.

Apoptosis↗
PubMed1997

Angiotensin II stimulates c-Jun NH2-terminal kinase in cultured cardiac myocytes of neonatal rats.

Many lines of evidence have suggested that angiotensin II (Ang II)plays an important role in cardiac hypertrophy. Ang II not only increases protein synthesis but also induces the reprogramming of gene expression in cultured cardiac myocytes. In the present study, to elucidate the mechanism by which Ang II regulates gene expression in cardiac myocytes, we examined whether Ang II activates c-Jun NH2-terminal kinase (JNK), which is a member of the mitogen-activated protein kinase family and activates the transcription factor, activator protein-1 (AP-1). The activity of JNK increased 5 minutes after the addition of Ang II, peaked at 20 minutes, and gradually decreased thereafter. Examination of the Ang II dose-response relation revealed detectable JNK activation at 10(-9) mol/L and maximal activation at 10(-6) mol/L. Ang II activated JNK through the AT1 receptor, and the activation was attenuated by the downregulation of protein kinase C or the chelation of intracellular Ca2+. Although the addition of either Ca2+ ionophore or phorbol ester resulted in little or no activation of JNK, simultaneous addition of both Ca2+ ionophore and phorbol ester markedly activated JNK. Slight expressions of the c-jun gene were observed in unstimulated cardiac myocytes, and Ang II increased expressions of the c-jun gene as well as the c-fos gene. Ang II increased transcription of the endothelin-1 gene through the AP-1 binding site. In conclusion, Ang II may activate JNK in cultured cardiac myocytes through an increase in intracellular Ca2+ and activation of protein kinase C, and the activated JNK may regulate gene expression by activating AP-1 during Ang II-induced cardiac hypertrophy.

Angiotensin II↗
PubMed1997

Synergistic effect of nitric oxide and vasoactive intestinal peptide on bronchoprotection against histamine in anesthetized guinea pigs.

Vasoactive intestinal peptide (VIP) and nitric oxide (NO) are considered to be nonadrenergic, noncholinergic (NANC) inhibitory neurostransmitters in the airways. It seems likely that these neurotransmitters may be coreleased and act as functional antagonists against bronchoconstrictor stimuli. In the present study, we examined the synergistic effect of NO and VIP on bronchoprotection against histamine in anesthetized guinea pigs. The NO donor, S-nitroso-N-acetylpenicillamine (SNAP) significantly inhibited histamine-induced bronchoconstriction in a dose-dependent manner. VIP also inhibited histamine-induced bronchoconstriction in a dose-dependent manner, but this bronchoprotective effect was short-lived. Additionally, VIP (10(-9) M) had no significant bronchoprotective effect, but a subthreshold dose of SNAP (10(-7) M) significantly potentiated VIP (10(-9) M)-induced bronchoprotection against histamine. Moreover, SNAP (10(-7) M) significantly enhanced VIP (10(-7) M)-induced bronchoprotection for a longer period of time. On the other hand, VIP (10(-9) M) also significantly potentiated SNAP-induced bronchoprotection against histamine. In conclusion, combination therapy with NO donor and VIP receptor agonist may have important advantages in the treatment of bronchial asthma, and both NO and VIP may contribute in complementary fashion to the NANC-induced relaxant response in guinea pig airways.

Anesthesia↗
PubMed1997

[Combined effect of adoptive immunotherapy (AIT) with lymphokine-activated killer (LAK) cells and interleukin-2 (IL-2) and chemotherapy in tumor-bearing mice].

We investigated beneficial effects of AIT with anticancer agents on survival of subcutaneous tumor-bearing mice and suppression of artificial lung metastasis, and optimal schedule of administration of each treatment in vivo. 7-8 weeks old C 57 BL/6 mice were inoculated s.c. with 5 x 10(6) B 16 melanoma cells, or i.v. with 2 x 10(5) B 16-F 10 melanoma cells. Mouse splenocytes were cultured with 3.5 x 10(3) JRU/ml interleukin 2 for 14 days, and induced LAK cells were harvested. Anticancer agents (Cx), CDDP or MMC were given i.p. in mice. 1 x 10(7) or 5 x 10(7) LAK cells were given either s.c. around the tumor or i.v. respectively, and 1.4 x 10(5) JRU/mouse IL-2 was administered s.c. for 6 days after LAK cell injection. Therapy groups were as follows #1: Cx day 3, AIT day 3-8. #2: Cx day 3, AIT day 6-11, #3: Cx day 8, AIT day 3-8. In therapy groups #1 and #2, we observed additive effects of AIT and anti-cancer agents in life-prolongation and suppression of lung metastasis. It was also shown that LAK induction in vivo was augmented by anticancer agents in groups #1 and #2, which might represent one of the mechanisms behind observed additive effects. Furthermore, our results suggest that therapeutic effects of the combination of AIT and anticancer agents depend on the schedule of administration.

Animals↗
PubMed1997

[Using "Care Note" to measure the level of satisfaction patients feel with their care, in palliative cancer care, as a measure of their quality of life].

In this study, a new Questionnaire, "Care Note", was developed for palliative cancer care and it was validated in relation to the level of satisfaction in their daily lives felt by patients during supportive care. Care Note and EORTC QLQ-C 30 were administered to 97 patients with various forms of malignant disease (mean age 61, M/F 73/24). They filled in a Care Note questionnaire twice a week, on average they completed 6.77 questionnaires (a total of 657 questionnaires). The average time to answer was 5.49 minutes, and patients compliance was good. Evaluation indices in the first examination (n = 97) were shown as: content validity, test-retest reliability, item-scale correlation revealed discriminant validity and convergent validity with internal consistency, using Cronbach in the range alpha = 0.695-0.814, were proved. Concurrent validity with EORTC QLQ-C 30 was satisfied. A multiple regression analysis showed that social well-being (p < 0.0001) and global quality of life (p = 0.0001) were explanatory valuables for expressing satisfaction in relation to daily life.

Adult↗
PubMed1997

[Clinicopathological findings in 5 patients with acute eosinophilic pneumonia].

We studied 5 patients with acute eosinophilic pneumonia. Radiologic findings were Kerley's lines and pleural effusion on chest X-ray films, and interlobular septa on chest CT scans. Examination of transbronchial lung biopsy specimens revealed infiltration of eosinophils and lymphocytes into alveolar walls and edema of alveolar walls, interlobular septa, and perivascular connective tissue. The findings of interstitial edema were consistent with the radiological findings. Epithelial damage and bud-type intraluminal fibrosis were also seen, but residual alveolar structure was maintained. Bronchoalveolar lavage fluid contained abnormally high percentages of eosinophils and lympocytes. It also contained basophils and mast cells, which were not seen in fluid from normal subjects. Fluid from patients with chronic eosinophilic pneumonia had significantly fewer basophils than did fluid from those with acute eosinophilic pneumonia (p < 0.01). These findings suggest that release of chemical mediators from basophils plays a key role in interstitial edema in acute eosinophilic pneumonia.

Acute Disease↗
PubMed1997

[A new reconstructive procedure, interposition of a jejunal pouch after proximal gastrectomy].

In this chapter we mention the significance or advantage of the new reconstructive procedure, interposition of a jejunal pouch after proximal gastrectomy. Instead of oesophagogastrostomy which often brought many postoperative complications, various techniques of anastomosis such as conventional jejunal interposition or double tract method were contrived. Although these techniques could reduce the incidence of postoperative problems such as reflux oesophagitis, it is very difficult to examine or remedy beyond the oesophagojejunostomy site after surgery. On the other hand, interposition of a jejunal pouch showed us many advantages. The volume of reconstructed stomach was adequate and the patients could eat enough actually. In case of need, endoscopic fiber could enter the remnant stomach or duodenum very easily. This is the big advantage for the treatment of the upper GI and hepato-biliary pancreatic diseases endoscopically or radiologically after proximal gastrectomy. For these reasons, we usually use interposition of a jejunal pouch between the oesophagus and remnant stomach after proximal gastrectomy.

Anastomosis, Surgical↗
PubMed1997

A new T-lymphocyte cloning assay for detection of in vivo mutations in the human hypoxanthine-guanine phosphoribosyltransferase gene.

The X-linked hypoxanthine-guanine phosphoribosyl transferase (hprt) gene is a target of analyses of in vivo mutation frequencies in circulating T-lymphocytes. We established a novel, accessory cell-free cloning method of T-lymphocytes with a hprt mutation by a combined use of recombinant interleukin-2, conditioned medium from activating T-lymphocytes and culture plates coated with anti-CD3 monoclonal antibody. Using the method, we examined mutation frequencies of the hprt gene in T-lymphocytes from six healthy individuals, nine patients with colon cancer including two patients from different families with hereditary nonpolyposis colon cancer and six cancer-free relatives of the patients. In six healthy individuals, the mean cloning efficiency and mutation frequency (MF) of the hprt gene in T-lymphocytes were 0.51 +/- 0.28 and 9.4 +/- 7.5 x 10(-6), respectively. These data were similar to the reported values. The mean MFs in the nine colon cancer patients (10.6 +/- 7.3 x 10(-6)) were not significantly different from those of the 12 cancer-free individuals (11.6 +/- 9.4 x 10(6)). The correlation between mutation frequencies and age of the individuals was significant regardless of the presence or absence of cancers. The single-strand conformation polymorphism analyses of nested RT-PCR products of hprt mRNA were done in 33 mutant clones from five members of a family of which MF values were high. All the analyzed mutant clones show a genetic aberration in the coding region of the hprt gene. At least 28 of 33 mutants were independent. Our method provides a new versatile tool for in vivo analysis for mutations of the hprt gene.

Adult↗
PubMed1997

UFT plus cisplatin in advanced non-small-cell lung cancer: interim analysis of 67 patients.

A single-institution phase II study indicated that combination chemotherapy using UFT (tegafur and uracil) plus cisplatin (Platinol) in patients with non-small-cell lung cancer was active with less host toxicity than other cisplatin-based therapies. To confirm these observations, the Japan JFT Lung Cancer Study Group conducted a multi-institutional phase II trial. The number of patients planned for this trial is 110. Eligibility includes previously untreated stage IIIB or IV non-small-cell lung cancer and a good performance status. UFT 400 mg/m2 in two divided doses is administered orally on days 1 through 14, and cisplatin 80 mg/m2 is injected IV on day 8. This treatment is repeated every 3 or 4 weeks. Between April 1995 and May 1996, 67 patients were enrolled, and all 67 were considered eligible for an interim analysis performed in October 1996. Among 63 patients evaluable for response, there was an overall response rate of 30% (95% confidence interval, 19% to 41%), with one complete response and 18 partial responses. With a median follow-up duration of 44 weeks, the median survival time was 32 weeks and the 1-year survival rate was 25%. Grade 3 leukopenia occurred in only 1 of 67 patients (1.5%), and there was no thrombocytopenia of grade 3 or greater. Vomiting, the most common nonhematologic toxicity observed, reached grade 3 or 4 in only 6 patients (9%). This interim analysis seems to support the observations of the previous single-institution phase II trial.

Aged↗
PubMed1997

[Relationship between exercise-induced hypoxemia and long-term survival in patients with chronic obstructive pulmonary disease].

In patients with chronic obstructive pulmonary disease (COPD), exercise-induced hypoxemia (EIH) is an important limiting factor of exercise performance, but there are very few reports of the prognostic value of EIH. We therefore examined whether EIH is related to long-term outcome in patients with COPD. We gathered data on survival of 77 patients with COPD who had undergone three-minute incremental treadmill exercise tests between 1979 and 1988. A plastic catheter was placed percutaneously into a brachial artery to measure arterial blood gases at each stage of exercise. Expired gas was analyzed continuously during exercise with a Respiromonitor RM-300 (Minato Medical Science). As an index of the severity of EIH we used the delta PaO2/delta VO2 (mmHg/L/min), PaO2-slope. Patients were assigned to two groups according to PaO2-slope, and actuarial survival curves were plotted for the two groups. The survival data were analyzed by generalized Wilcoxon analysis. Survival was significantly better in the group with low PaO2-slopes (< 20 mmHg/L/min) than in the group with high PaO2-slopes (> or = 20 mmHg/ L/min) (p = 0.0031). Also, among the patients in whom PaO2 during exercise was less than 60 mmHg, there was a significant difference in survival between those who received home oxygen therapy and those who did not. We conclude that the degree of EIH can be used to predict survival in patients with COPD, and that the degree of EIH should be considered when prescribing continuous home oxygen therapy for these patients.

Aged↗
PubMed1997

[Analysis of pulmonary manifestations in patients with rheumatoid arthritis].

We studied chest X rays of 911 patients with rheumatoid arthritis (RA). The findings showed interstitial shadow in 28 patients (3.1%), pleuritis in 13 patients (1.4%) and nodular shadow in 3 patients (0.3%). RA patients with interstitial pneumonia were commonly male and older. And they had significantly high levels of rheumatoid factor (RF), RAPA and IgG-RF in serum, but they were not associated with high score of Lansbary index. All patients with more than 1500 IU/ml in RF value had a complication of interstitial pneumonia. These results suggest the importance of chest X-ray in the management of RA patients with high titer in RF.

Aged↗