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T Tsunoda

Publications and source records attributed to T Tsunoda.

At least 199 records · Page 11Linked to original sources

Distinguishing pancreatic carcinoma from other periampullary carcinomas by analysis of mutations in the Kirsten-ras oncogene.

The prevalence of Kirsten (Ki)-ras gene mutations was studied in 105 paraffin-embedded tissues obtained from 40 patients with pancreatic cancer, 48 with bile duct carcinoma (19 distal, 6 middle, and 23 proximal), 16 with ampullary carcinoma and 1 with duodenal cancer, by in vitro amplification of target sequences by the polymerase chain reaction (PCR). With regard to pancreatic cancers, the authors' data confirm the very high frequency (88.6%) of Ki-ras gene mutations occurring at codon 12. Five pancreatic carcinomas did not contain the Ki-ras mutation and included rare types of histopathology. By histologic review after the examination of Ki-ras mutations through PCR, the diagnosis of four patients could be legitimately revised from other periampullary carcinoma to pancreatic carcinoma. In the ampullary carcinoma, the prevalence of mutations in Ki-ras codon 12 was 13.3%. Although there was a large difference in incidence of mutations between distal and middle or proximal bile duct carcinoma, the prevalence of mutations in bile duct carcinoma was limited to 19.6%. Unlike other approaches to diagnose periampullary carcinoma, detection of a mutation in Ki-ras codon 12 by PCR may distinguish pancreatic carcinoma from other periampullary carcinomas that have better prognoses.

Aged↗

Solid and cystic tumor of the pancreas in an adult male.

A solid and cystic tumor (SCT) was located at the head of the pancreas in a 43-year-old Japanese male, and pancreatoduodenectomy was performed on the suspicion of papillary carcinoma or cystadenocarcinoma of the pancreas. The lesion, which measured 4.5 x 4.5 x 4.0 cm, was clearly demarcated by connective tissue. The cut surface showed solid grayish-white areas with central cystic degenerative changes. The solid areas consisted of small round cells proliferating in a small solid or a pseudopapillary pattern. The tumor cells partially invaded the surrounding normal pancreatic parenchyma. Immunohistochemical studies revealed positive staining for alpha-1-antitrypsin and neuron-specific enolase, but no staining for known pancreatic hormones. Moreover, ultrastructural studies showed the absence of zymogen granules and the presence of anullate lamellae and neurosecretory granules. On the basis of these findings, a diagnosis of SCT of the pancreas was established. In order to clarify the histogenesis and biological behavior of the tumor, it is necessary to accumulate and analyze similar cases, an endeavor which in turn will contribute to the successful management of this disease.

Adult↗

[Effect of sparfloxacin on fecal microflora and its fecal concentration in patients with bacillary dysentery].

The effect of sparfloxacin (SPFX) on fecal microflora and its fecal concentrations were examined in four patients and one carrier with bacillary dysentery. SPEX was administered to five cases with a daily dose of 200 mg, once a day, for five days after breakfast. The results were as follows: Escherichia coli, a main bacterium in Enterobacteriaceae, was not detected during the drug administration, except one from whose feces mucoid type of E. coli was found all the time, and the colony forming units (CFUs) were not recovered to the initial level at the seventh day after the medication. Enterococcus, found in all of the cases before, was eliminated or decreased during and the CFUs showed slow recovery after the medication. Total CFUs of aerobes were decreased during and not returned to the initial level at the seventh day after the medication. Total CFUs of anaerobes were kept invariable, although variation of the CFUs with the species was seen. The peak levels of the fecal concentrations of SPEX were 177 to 535 micrograms/g on the third to the fifth day of the medication. The fecal concentrations were 1.3 to 4.4 micrograms/g at the seventh day after the medication in all of the cases. The clinical efficacy was excellent in three cases, poor in one evaluated for the other bacteria than Shigella, and unknown in one. No adverse reaction was observed.

Adult↗

[A clinical experience of rokitamycin on Campylobacter enteritis. Research Group of Rokitamycin on Infectious Enteritis].

Rokitamycin, a newly developed macrolide, was administered to a total of 107 cases, 16 years old or more, in order to evaluate its clinical efficacy, safety and usefulness on Campylobacter enteritis. Daily dosage of 600 mg of rokitamycin was administered orally in three divided doses for 5 days. Bacteriological and clinical efficacies were judged by the attending doctors from the evaluation criteria made by the committee and from the days required for improvement of diarrhea, defervescence and so on, respectively. Antibacterial activities against the isolates were tested of rokitamycin (RKM), erythromycin (EM), josamycin (JM) and ofloxacin (OFLX). The results were as follows; 41 symptomatic patients and 5 carriers were evaluated. Clinical efficacy (n = 41) was 100% (excellent; 34.1%, good; 65.9%). Bacteriological efficacy (n = 41) was 97.6%. Eight of the 9 cases with consecutive stool cultures were free of the bacteria on and after one day of the drug administration. Clinical usefulness (n = 46) was 97.8%. Slight epigastric pain was seen in only one as a side effect. The items of abnormal laboratory findings were 4 elevated GPT and/or GOT and one increased number of WBC in 4 cases. MIC90 of RKM, EM, JM and OFLX against 41 clinical isolates of C. jejuni were 1.56, 3.13, 3.13 and 0.78 micrograms/ml, respectively. Rokitamycin was considered clinically useful to treat Campylobacter enteritis.

Adolescent↗

[Comparison of clinical efficacy of rokitamycin (RKM) and ofloxacin (OFLX) for the treatment of Campylobacter enteritis by a double-blind method. The Research Committee for the Effect of Rokitamycin, Research Group for Infectious Enteritis].

The clinical efficacy, safety and usefulness of Rokitamycin (RKM), a new macrolide antibiotic, were compared with those of Ofloxacin (OFLX) for the treatment of Campylobacter enteritis by a double blind method. The daily dose level of RKM or OFLX was 600 mg. They were orally administered in three divided doses for 5 days. Of 223 cases studied, 106 cases were diagnosed as Campylobacter enteritis. Ninety cases (RKM group: 50, OFLX group: 40) except for 16 excluded or drop-out cases were analysed. There was no significant difference between the two groups in any background factors. The effectiveness and usefulness was evaluated in 88 cases (RKM group: 48, OFLX group: 40). The results obtained were as follows: 1. In a total of 82 strains of Campylobacter jejuni/coli (RKM group: 42, OFLX group: 40), the bacteriological efficacy rate of RKM (95.2%) was superior to that of OFLX (70.0%) with a significant difference (p = 0.006). 2. In 76 symptomatic patients (RKM group: 42, OFLX group: 34) on the day of the beginning of drug administration, the clinical efficacy rate was 97.6% in the RKM group and 85.3% in the OFLX group with no significant difference between the two groups. 3. In 88 evaluable patients, the global clinical efficacy rate of RKM (95.8%) was superior to that of OFLX (67.5%) with a significant difference (p = 0.001). 4. Side effect was observed in 1 (1.9%) of the 54 patients in the RKM group and none of the 44 patients in the OFLX group. Slightly abnormal laboratory findings were seen in 4 (10.8%) of the 37 patients treated with RKM and 3 (9.7%) of the 31 patients treated with OFLX, but there was no significant difference between the two groups. 5. In 88 evaluable patients, the clinical usefulness of RKM (91.7%) was superior to that of OFLX (67.5%) with a significant difference (p = 0.01). From these results, RKM is considered to be a very useful agent for the treatment of Campylobacter enteritis.

Adolescent↗

[Relations of serum apolipoprotein A-I, A-II and B levels to smoking, drinking and body mass].

To examine whether the serum apolipoprotein A-I level (Apo A-I), serum apolipoprotein A-II level (Apo A-II) and serum apolipoprotein B level (Apo B) are related to cigarette-smoking habits, drinking frequency and body mass index (BMI) independent of serum lipoprotein cholesterol levels (HDLC, LDLC or VLDLC), we statistically analyzed the data on Apo A-I, Apo A-II, Apo B, HDLC, LDLC and VLDLC and the life style data obtained from health examinations of 256 male residents aged 40 to 49 mostly randomly selected from two Japanese areas, Ninohe, Iwate and Ishikawa, Okinawa. The results were as follows: (1) HDLC was strongly positively correlated with Apo A-I and Apo A-II, while Apo B was strongly correlated with LDLC and VLDLC. (2) According to univariate analyses, Apo A-I, Apo A-II, Apo B, HDLC, LDLC and VLDLC were not associated with smoking. On the other hand, drinking frequency was positively associated with Apo A-I, Apo A-II and HDLC. Apo A-I and HDLC were negatively correlated with BMI, whereas Apo B, LDLC and VLDLC were positively correlated with BMI. (3) According to the results of multi-dimensional analyses of covariance, Apo A-II was positively correlated with drinking frequency independent of Apo A-I and HDLC, especially among the individuals with increased HDLC. The same multivariate analysis showed that Apo B was positively associated with smoking independent of LDLC and VLDLC among the individuals without increased VLDLC. From these results, we conclude that Apo A-II may be effective as a biological marker for alcohol drinking independent of Apo A-I and HDLC, while cigarette smoking may affect Apo B through a certain direct mechanical effect. (4) Increased HDLC in obese individuals (BMI greater than or equal to 27) or non-drinkers was associated with remarkably increased Apo A-I, while decreased HDLC in thin individuals (BMI less than 21) was associated with remarkably decreased Apo A-II.

Adult↗

Early in vitro detection of interleukin-2-like activities by pretreatment with allogeneic blood lymphocytes in miniature swine.

In order to determine the means of monitoring the immunological status of allograft recipients in miniature swine, an assay was developed to measure interleukin (IL)-2 production in vitro by pretreatment of donor peripheral blood lymphocytes (PBL). Miniature swine were given 0 to 4 weekly intravenous transfusions of 5-10 X 10(7) donor PBL incompatible at major histocompatibility complex (MHC) and assayed in vitro for donor specific immune IL-2-like activities. The results are summarized as follows: (1) IL-2-like activity in 24 hr and 48 hr supernatants from mixed lymphocyte cultures (MLC) with MHC-incompatible PBL was detected without pretreatment. The 48 hr MLC supernatant exhibited a high IL-2-like activity compared with the 24 hr; (2) IL-2-like activity after only one transfusion with MHC-incompatible PBL was higher than that without pretreatment; (3) IL-2-like activity in 4 weekly transfusions was detectable slightly earlier than that without pretreatment or three transfusions with MHC-incompatible PBL.

Animals↗

Cisplatin treatment renders tumor cells more susceptible to attack by lymphokine-activated killer cells.

We investigated whether tumor cell lysis by lymphokine-activated killer (LAK) cells was enhanced by treatment of the tumor cells with cisplatin (CDDP) in vitro. Tumor cells were treated with CDDP in vitro, and the cytotoxic activity for LAK cells was measured by 4-h 51Cr-release assay. The alterations of succinate dehydrogenase (SD) activity, and DNA,RNA synthesis of tumor cells were analysed. The susceptibility of CDDP-treated (2 micrograms/ml, 2h) Daudi and KATO-III cells to lysis by short term-cultured LAK cells was enhanced, as was the susceptibility of CDDP-treated (2 micrograms/ml, 12h) autologous tumor and Daudi cells to lysis by long term-cultured LAK cells. SD activity and DNA synthesis in tumor cells were impaired by 12-h treatment with 2 micrograms/ml of CDDP, whereas those were not altered by 2-h treatment with 2 micrograms/ml of CDDP. The enhancement of the susceptibility of CDDP-treated tumor cells to long term-cultured LAK cells was thus elucidated; it was shown to be due to alterations of the tumor cells with regard to their SD activity and DNA synthesis. It is suggested that the combined therapy with CDDP and LAK cells offers hope for increasing the response rate and the long-term survival of cancer patients.

Cisplatin↗

[5-Fluorouracil level and pyrimidine nucleoside phosphorylase activity in cancer patients after oral administration of doxifluridine (5'-DFUR)].

For the purpose to evaluate the distribution of 5'-DFUR in the cancerous tissues and non-cancerous tissues of 64 cancer patients (21 gastric, 25 colo-rectal and 18 breast cancers), pyrimidine nucleoside phosphorylase (PyNPase) activity and 5-FU level were determined by bioassay and GC-MS method. 5-FU levels in the plasma were also measured in all patients. Four hundred mg of 5'-DFUR was orally administrated three times a day for 3 to 7 days and just 3 hours before surgical operations. PyNPase activity and 5-FU level were significantly higher in the cancerous tissues than non-cancerous ones. 5-FU levels in the plasma were significantly lower than those in both cancerous and non-cancerous tissues. In conclusion, 5'-DFUR is expected to be an useful anticancer drug because of the selective accumulation of converted 5-FU in cancerous tissues.

Adenocarcinoma↗

[Detection of point mutation of Kirsten ras oncogene in pancreatic carcinoma by polymerase chain reaction].

Regarding to the pancreatic cancer, outcomes of the patients surgically treated have been poor. By using polymerase chain reaction (PCR), paraffin-embedded specimens of the pancreatic carcinoma were confined point mutation in Kirsten (K)-ras codon 12. Then, incidence and type of point mutation of this oncogene and correlative studies with stage, T or N factor of pancreatic cancer were analysed. Extremely high incidence of K-ras gene mutation was shown in present report. The highest mode of point mutation of K-ras oncogene was GGT to GAT coded aspartic acid. Cases without point mutation in K-ras codon 12 were significantly frequent in papillary adenocarcinoma than in tubular type. There were not correlative result among mutation types, stage and T factor of pancreatic cancer. Most patients with pancreatic cancer who survived more than 2 years have not shown mutation to aspartic acid. Four cases including two cases of mucin producing pancreatic cancer did not have point mutation in K-ras codon 12. Pathogenesis of mucin producing cancer can be distinguished from typical pancreatic cancer by detection of point mutation in K-ras codon 12 using PCR.

Codon↗

Mutations in the Kirsten-ras oncogene are common but lack correlation with prognosis and tumor stage in human pancreatic carcinoma.

Utilizing the polymerase chain reaction (PCR), we studied the presence and pattern of mutations in the Kirsten (Ki)-ras oncogene, using paraffin-embedded sections of pancreatic carcinoma tissue from 53 patients. Mutations in the Ki-ras oncogene were evident in 46 of the 53 patients (87%) in codon 12. The predominant mutation was from glycine (GGT) to aspartic acid (GAT). Among the 46, one had an additional mutation in Ki-ras codon 13, and no mutation was found in codon 61. These oncogenetic mutations were observed even in early stage pancreatic carcinoma, and there was no statistically significant difference in the rate or positivity of mutations among the stages of the disease. With regard to patient survival, statistical analysis comparing 37 patients with mutations in the Ki-ras oncogene and four patients without mutations revealed no significant difference. These results suggest that mutations in the Ki-ras oncogene may be related to the initiation of carcinogenesis, but are not linked to malignant potential or promotion of human pancreatic cancer.

Adenocarcinoma↗

[Combination of adoptive immunotherapy and chemotherapy against advanced cancer with peritoneal dissemination].

In a case of advanced gastric cancer with bilateral Krukenberg's tumors and peritonitis carcinomatosa, total gastrectomy, splenectomy and bilateral oophorectomy was performed. Since progressive peritoneal dissemination was recognized, 150 mg of CDDP and 10 mg of MMC which were proved to be effective by chemosensitivity test of anticancer drugs were administered intraperitoneally. After one month, ascites increased. So LAK cells and TIL were transferred intraperitoneally 6 times. With this treatment ascitic collection remarkably decreased, the performance status improved and serum level of IAP and CA125 normalized. Thus, it is clarified that the combination of adoptive immunotherapy and chemotherapy possesses therapeutic efficacy against advanced gastric cancer with peritonitis carcinomatosa.

Adenocarcinoma, Mucinous↗

Clinical evaluation of chemotherapy under angiotensin II-induced hypertension in patients with advanced cancer.

The clinical efficacy and indications for Angiotensin II (AT II)-induced hypertension chemotherapy were evaluated as a drug delivery system in 101 patients with advanced carcinoma. The sites of primary tumor studied included stomach (44), pancreas (18), colon (16), esophagus (6), bile duct (4), liver (3), breast (7) and 3 other single organs. Seventy four cases had distant metastases (lymph node (25), liver (29), peritoneum (16), and lung (4)). Additionally, the protocol was used 12 cases as postoperative adjuvant chemotherapy and 15 cases following exploratory laparotomy. The blood pressure was elevated to a level 1.5 times base-line. The regimens used consisted of MMC + ADR (55), FAM (38) and CDDP (8). The dosages administered were MMC 7 mg/m2, ADR 14 mg/m2 and 5-FU 350 mg/m2. The cancer chemotherapy protocol with AT II was repeated for an average of 2.6 cycles with a 2-3 week interval. The drug concentration in tumor tissues was increased 1.7 fold by AT II treatment. The response rate was 15.8% (CR 7 and PR 9), and in those patients with lymph node, liver and peritoneal metastases was 48.0, 6.9 and 6.3%, respectively. The serum levels of tumor markers decreased in 9 patients. Subjective symptoms, such as hoarseness, edema and pain, were improved. The mean survival in patients with distant metastasis who responded was 343 days, and in nonresponders was only 168 days (p less than 0.05). The side effects of this therapy were slight, typically being grade 1 and 2. Thus, the chemotherapeutic agents studied in conjunction with AT II were effective in patients with lymph node metastasis. Additionally, this regimen could be performed safely with minimal side effects.

Aged↗

[Augmentation of cytotoxic activity by combination with interleukin 2 and interferon gamma].

The synergy of cytotoxic activity by Interleukin 2 (IL-2) and Interferon gamma (IFN-gamma) was evaluated in human peripheral blood mononuclear cells (PBMC) and spleen cells. PBMC incubated with IL-2 (10 IU/ml) and IFN-gamma (200 IU/ml) for 4 days showed the maximum cytotoxic activity against K562, MOLT-4 and Daudi cells. Combination with IL-2 and IFN-gamma induced stronger activity than IL-2 or IFN-gamma alone. In order to investigate the sequential roles of IL-2 and IFN-gamma in the synergy of killer cell function, IFN-gamma was stimulated after washing-out IL-2 or stimulated at various timing and duration without washing-out IL-2. IL-2 was essential to induce the synergistic effect of IL-2 and IFN-gamma to killer activity. The similar augmentation of killer activity was observed by the addition of IFN-gamma at any incubation period with IL-2, compared with that of stimulations IL-2 and IFN-gamma stimulation. The phenotypes of the killer cells by stimulation of IL-2, IFN-gamma alone or IL-2 and IFN-gamma were mainly CD2+, CD16+, namely, the phenotype of activated natural killer cells.

Cytotoxicity, Immunologic↗

Antifungal drugs affect adherence of Candida albicans to acrylic surfaces by changing the zeta-potential of fungal cells.

The effect of sub-inhibitory concentrations of antifungal drugs on the adherence of Candida albicans to acrylic surfaces was investigated. Among five antifungals tested, azalomycin F and aculeacin A significantly enhanced the adherence. The zeta-potential of fungal cells was affected by antifungal drugs, whereas no significant change in cell surface hydrophobicity was observed. The relationship obtained between the change in the adherence and that in zeta-potential suggests that the enhanced adherence was caused by decreased electric repulsive forces.

Acrylates↗

[Clinical application of adoptive immunotherapy by cytotoxic T lymphocytes induced from tumor-infiltrating lymphocytes].

The tumor-infiltrating lymphocytes (TIL) were cultured with interleukin 2 (IL-2) to induce the cytotoxic T lymphocytes possessing autologous tumor-killing activity from 21 cancer patients (11 with solid tumor and 10 with malignant peritoneal or pleural effusions), and transferred into 7 patients as IL-2-activated TIL adoptively. The clinical application of activated TIL by adoptive transfer could result the complete regression of malignant pleural effusions in a patient with pancreatic cancer, and the nearly complete regression of malignant ascites in a patient with gastric cancer. The autologous tumor cells were isolated at the purity of more than 90% by Ficoll-Hypaque and Percoll discontinuous gradients, and then the TIL were cultured with IL-2 until 4 weeks. The optimal concentration of IL-2 was 1,500 IU/ml to obtain maximum proliferation and autologous tumor killing activity. The cytotoxic activities of activated TIL at 3 weeks-incubation was 72 +/- 15, 42 +/- 26, 27 +/- 21 and 22 +/- 15% against K562, Daudi, KATO-III and autologous tumor, respectively. By negative selection method, it was clarified that the killer cells recognizing autologous tumor consisted of CD4 or CD8 positive T lymphocyte in 43% of patients. The CD8 positive cells and CD56 positive cells increased, the CD4 positive cells and CD16 positive cells decreased by flow cytometry. The activated TIL could lyse not only cultured tumor cell lines, also other autologous tumor cells. The CD56+ cells were isolated by the Panning method, these cells could not lyse autologous tumor cells. Thus, it was indicated that the cytotoxic T lymphocytes recognizing autologous tumor could be generated from TIL and the adoptive immunotherapy of activated TIL was effective in cancer therapy.

Adult↗

[Defective autologous mixed lymphocyte reaction (AMLR) in gastric cancer patients].

Autologous mixed lymphocyte reaction (AMLR) is an important reaction regulating the immune system in the various diseases. This is the first report investigating AMLR not only in peripheral blood but also in the spleen of gastric cancer patients. AMLR in the spleen of gastric cancer patients was significantly suppressed compared with that of peripheral blood of gastric cancer patients and patients without cancer. In investigation of AMLR composed of peripheral blood cells and spleen cells of gastric cancer patient, AMLR on splenic non-T cells as a stimulator was significantly suppressed compared with peripheral blood non-T cells as a stimulator. It suggests that abnormalities of non-T cells caused suppression of AMLR in the spleen of gastric cancer patients.

Female↗