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Biomedical subjects

Y Kanda

Publications and source records attributed to Y Kanda.

At least 217 records · Page 12Linked to original sources

[Analysis of platelet-activating factor and its effect on the lung].

One of the lipid mediators, platelet-activating factor (PAF), is reported to be involved in a variety of biological phenomena including not only harmful reactions such as allergy or inflammation, but also physiological phenomena like nerve cell differentiation, sperm mobilization, ovulation, implantation, parturition etc. We reviewed the methods of detecting PAF in biological fluids and the effects of PAF on fetal lung maturation and pulmonary diseases. Fetal lung has a capacity to produce PAF and this autacoid is involved in glycogen breakdown to furnish both glycerol backbone, such as dihydroxyacetone phosphate and glycerol-3-phosphate, and the fatty acids utilized to synthesize pulmonary surfactant. PAF also enhances secretion of pulmonary surfactant. However, PAF causes eosinophil recruitment to the lung, activation of eosinophil and neutrophil, bronchoconstriction, and lung edema, and increases bronchial hyperreactivity. All are characteristics of the pathophysiology of bronchial asthma. We examined PAF acetylhydrolase activity in plasma from patients with bronchial asthma, and found the activity was significantly lower in severe cases than that in mild or moderate cases. Ketotifen had no effect on this enzymatic activity. Evaluating PAF acetylhydrolase activity may help determine the severity of bronchial asthma. PAF is also involved in chronic lung disorders of newborns, such as bronchopulmonary dysplasia. We treated a 3-month-old child with frequent pulmonary problems who was made a diagnosis of bronchopulmonary dysplasia during neonatal period. After administration of Ketotifen for one and a half months, his clinical symptoms improved dramatically.

Animals↗

[A new sequential chemotherapy of methotrexate with 5-fluorouracil against advanced colo-rectal cancer].

A new sequential chemotherapy consisting of intravenous (IV) administration of methotrexate (MTX) 50 mg/m2 followed by 3 equal IV doses of 5-fluorouracil (5-FU) 500 mg/m2 at 1.4 and 21 hrs. and a leucovorin rescue (15 mg/body/8 hr) from 24 hrs. after MTX for 3 days was applied every two weeks for the patients with advanced colo-rectal cancer. The effectiveness of this MTX/3-dose 5-FU regimen was compared retrospectively with that of the standard sequential regimen consisting of the IV administration of MTX 100 mg/m2 followed by a single IV dose of 5-FU 800 mg/m2 one hr. later and a leucovorin rescue (21 mg/body/6 hr) 24 hrs. later given every week, namely MTX/1-dose 5-FU regimen. Partial response was achieved in 7 (46.7%) of 15 evaluable patients with the MTX/3-dose 5-FU regimen and in 3 (13.6%) of 22 evaluable patients with the MTX/1-dose 5-FU regimen (p < 0.05). The median survival times were 13 and 9 months, respectively. There were no significant difference in the patient characteristics between the two groups, and the toxic effects were much lower in the MTX/3-dose 5-FU than in the MTX/1-dose 5-FU regimen. It is therefore, concluded that the MTX/3-dose 5-FU regimen is superior to the standard MTX/1-dose 5-FU regimen.

Adult↗

New potent mitomycin derivatives: synthesis and antitumor activity of 7,7-(ethylenedioxy)mitomycins.

A series of 6,7-dihydro-7,7-(ethylenedioxy)mitomycins was synthesized and evaluated for antitumor and anticellular activities. These compounds were prepared by basic treatment of 7-methoxymitomycins with ethylene glycol, and were structurally novel mitomycin derivatives containing a masked quinone moiety. 5,6-Enol or 6-chloro derivatives of 6,7-dihydro-7,7-(ethylenedioxy)mitomycins were also prepared and the (allyloxy)carbonyl group at the aziridine nitrogen has proved to be an efficient protecting group in chemical modification of mitomycins. Most of these mitomycin derivatives displayed potent antitumor activity against P388 leukemia in mice and anticellular activity against HeLa S3 cells.

Animals↗

N.m.r. study on the formation and geometry of inclusion complexes of 6-O-(alpha-maltosyl)cyclomalto-hexaose and -heptaose with p-nitrophenol in aqueous solution.

The formation and molecular geometry of inclusion complexes of some branched cyclomaltaoses with p-nitrophenol in aqueous solution have been investigated by using high-resolution 1H-n.m.r. spectroscopy. 6-O-(alpha-Maltosyl)cyclomalto-hexaose and -heptaose were found to form 1:1 inclusion complexes with p-nitrophenol, and the dissociation constants for their complexes are quite similar to those for corresponding unbranched cyclomaltaose-p-nitrophenol complexes, indicating that formation of these inclusion complexes is not hampered by the maltosyl branch. From measurement of nuclear Overhauser enhancements, it was concluded that the maltosyl branch is not situated over the entrance of the cavity.

Carbohydrate Sequence↗

Usefulness of preoperative low dose cisplatin treatment for advanced esophageal cancer.

In order to decrease the perioperative complications by preoperative cisplatin chemotherapy, the preoperative single administration of cisplatin (30 mg/m2) was performed weekly from one to six times in 36 consecutive patients with esophageal cancer classified as higher than Stage II. The survival curve of 17 patients in Stage III was significantly better (P < 0.05) than that of patients who had been treated without preoperative cisplatin treatment. In 3 of the 12 patients who had locally invasive cancer, either the main tumors or the metastatic lymph nodes, which had invaded the trachea or the left main bronchus, sufficiently receded, so that a curative esophagectomy became possible; 2 of them have survived over 33 months while 1 died of pneumonia 33 months after surgery. The number of perioperative complications was minimal, and thus, we consider that the postoperative use of cisplatin and fluorouracil is indicated in patients in whom a histological response is noted in the resected specimens.

Aged↗

Antitumor activity of 7-N-[[2-[[2-(gamma-L-glutamylamino)ethyl]dithio]ethyl]]-mitomycin C.

Through the extensive investigation of new mitomycin C (MMC) derivatives, several compounds with disulfide at N-7 were found to show activities superior to MMC against murine Sarcoma 180 solid tumor. Among them, 7-N-[[2-[[2-(gamma-L-glutamylamino)ethyl]dithio]ethyl]]- mitomycin C (KW-2149) was selected for further evaluation of antitumor activity and toxicity in mice. KW-2149 exhibited activity superior to MMC in increasing survival of i.p. inoculated P388 leukemia-, M5076 sarcoma-, and B16 melanoma-bearing mice. KW-2149 administered i.v. also exhibited superior activity in inhibiting the growth of s.c. inoculated P388 leukemia, M5076 sarcoma, and colon 26 adenocarcinoma and in increasing survival of i.v. inoculated P388 leukemia- and M5076 sarcoma-bearing mice. Furthermore, KW-2149 remarkably increased the life span of MMC-resistant P388 leukemia- and L1210 leukemia-bearing mice. KW-2149 and MMC inhibited the growth of human tumors inoculated into nude mice. The activity of KW-2149 was prominent in human lung carcinoma Lu-65 and Lu-99, bladder carcinoma T24, and epidermoid carcinoma A431. KW-2149 was comparable to MMC in decreasing the number of WBC in the peripheral blood, and the thrombopenia induced by KW-2149 was mild and recovery was rapid. The in vitro anticellular spectrum of KW-2149 against 23 human tumor cell lines was similar to that of MMC. However, KW-2149 inhibited the growth of the cell lines at concentrations of 10- to 100-fold lower than MMC and showed efficient cytotoxicity against MMC-insensitive tumor cell lines. These included lung epidermoid carcinoma Calu-1, stomach carcinoma MKN-28, colon adenocarcinoma DLD-1, colon adenocarcinoma LoVo, bladder carcinoma HT-1197, sarcoma G-292, and melanoma SK-MEL-28 cells. These results indicate that KW-2149 bears interesting characteristics as a new anticancer drug and warrants further development.

Animals↗

[Protein-free culture of esophageal cancer cell lines].

We have established 13 esophageal cancer cell lines capable of growing in a protein-free environment. The growth of these cells was not affected by conditioned medium, but the growth of NIH3T3 cells and human fibroblasts was stimulated by conditioned medium. On the other hand, conditioned medium inhibited the growth of human endothelial cells. Amplified int-2 oncogene correlated well with the growth of cells in a protein-free environment but the number of EGF receptors and growth effect of EGF did not relate to such growth. Esophageal cancer cells grow automatically, possibly involving mesenchymal cells via the paracrine system. This results in a poor prognosis in patients.

Cell Division↗

Chemiluminescent method for continuous monitoring of nitrous acid in ambient air.

A continuous-flow method for measuring atmospheric HNO2 concentration in real time has been developed that uses a chemiluminescent NOx monitor. A Na2CO3 solution strips gaseous HNO2 from the atmosphere by means of pulling an air sample and the solution through a glass coil and mixing continuously with ascorbic acid solution which reduces nitrite to NO. The mixture is led into a gas-liquid separating coil consisting of microporous PTFE tubing. The NO evolved from the separating coil is swept out by a stream of clean air and detected with a chemiluminescent NOx monitor. The technique utilizes a dual flow system and dual channel NOx monitor to correct positive interferences from NO2 and peroxyacetyinitrate (PAN). The concentration of HNO2 is determined by difference between the two measurements. Sensitivity of the method is a function of the ratio of sampling flow rate to carrier gas flow rate, which permits readily a highly sensitive measurement.

Air↗

Utilization of vitamin A in rats with inflammation.

Reductions in the concentration of retinol (vitamin A) in serum, lung and kidney were observed in rats subjected to inflammation-inducing treatments (turpentine oil injection of thermal injury). At the same time, the liver showed an almost normal vitamin A content. Feeding of retinol to vitamin A-depleted rats with inflammation revealed that intestinal absorption of retinol was still active in the inflamed state, and the livers of these rats showed good incorporation of retinol. The livers of normal and vitamin A-depleted rats subjected to the inflammatory treatments showed a normal RBP content (retinol-binding protein) and hepatic release of holo-RBP into the serum was not impaired functionally. These results suggest the possibility that the decreases of vitamin A in the lung, serum and kidney may be due primarily to enhanced local consumption of vitamin A related to the inflammation, rather than to a reduced supply of vitamin A from the liver or to decreased intestinal absorption. In bovine serum albumin (BSA)-sensitized rats produced by direct intubation of BSA into the lungs, the level of vitamin A in the lung decreased prior to that in the liver or serum, supporting the hypothesis that the decrease in vitamin A in the inflamed lungs of these rats may be due mainly to the consumption of vitamin A in the lung in response to inflammation.

Animals↗

A phase II study of etoposide in patients with hepatocellular carcinoma by the Tokyo Liver Cancer Chemotherapy Study Group.

Twenty-four patients with hepatocellular carcinoma were treated with 80 mg etoposide/m2 for five consecutive days at 4-week intervals. Of the 21 patients evaluated, only one showed a partial response (of 8 weeks, duration). The dose-limiting factor was bone marrow suppression. Grades 3 and 4 white blood cell count toxicity occurred in five (24%) and two (10%) patients, respectively. Alopecia (grades 1 and 2) was observed in 18 patients (57%). The The present study indicates that etoposide has very limited activity against hepatocellular carcinoma.

Aged↗

[A case of hepatocellular carcinoma (HCC) with lung metastasis which responded to chemotherapy with a single use of 1-hexylcarbamoyl-5-fluorouracil (HCFU)].

To our knowledge, there has been only one report pertaining to the efficacy of HCFU for treatment of metastatic lung lesion of HCC, so we reported a case of HCC with lung metastasis which responded to chemotherapy with a single use of HCFU. A 64-year-old male was diagnosed as having HCC with lung metastasis by biochemical examination, abdominal CT, hepatic arteriogram and chest X-P. He had been treated previously with gamma-interferon and mitoxantrone, which were assessed as NC and PD, respectively. Two months after last chemotherapy, HCFU was administrated at a dose of 400 mg/body everyday for 8 months. After 4 weeks metastatic lung lesions showed remarkable regression (47% decrease) and disappeared completely 9 weeks later. The size of primary liver tumor gradually decreased during therapy and revealed marked improvement (85.7% decrease) after about 2 months of this therapy. During these periods serum levels of alpha-fetoprotein dropped from 430 ng/ml to less than 10 ng/ml. He is presently still alive and the duration of the PR attained to 35 weeks. As side effects, hypoproteinemia, anorexia and hot sensation were observed.

Antineoplastic Agents↗

Plasma levels of leukotriene C4, B4, slow reacting substance of anaphylaxis in chronological phases of cerebrovascular disease.

In this study we report and compare plasma leukotriene (LT) levels in seventeen (17) patients with cerebral infarction, five (5) patients with cerebral hemorrhage and twelve (12) age-matched healthy volunteers. Plasma samples were collected at intervals of 1-7 days, 8-14 days, 15-30 days and 31 days- after cerebrovascular accident. Plasma immunoreactive LTC4, LTB4 and SRS-A (Slow Reacting Substance of Anaphylaxis or total peptido-LT's) levels were measured for each sample. Immunoreactive LTC4 (and SRS-A) levels were elevated in patients with cerebral infarction whilst LTB4 levels were raised in the patients with cerebral hemorrhage. In particular, cerebral infarcted patients exhibited significantly elevated levels in phases 1-7 days and after 15 days when compared with the age-matched healthy volunteers. In patients with cerebral hemorrhage, significant increases in LTB4 were measured in days 1-7 only. These results suggest a clinical relationship between the plasma levels of LT's and cerebrovascular disease.

Adult↗

Brain eicosanoid levels in spontaneously hypertensive rats after ischemia with reperfusion: leukotriene C4 as a possible cause of cerebral edema.

The relation of brain eicosanoids to progression of cerebral edema was studied in stroke-resistant spontaneously hypertensive rats subjected to incomplete global brain ischemia induced by bilateral occlusion of the common carotid arteries. Thromboxane B2 and 6-keto prostaglandin F1 alpha levels were significantly elevated 5 minutes after reperfusion but returned to control levels by 30 minutes. In contrast, leukotriene C4 levels increased 2 hours after bilateral common carotid artery occlusion and peaked 30 minutes after reperfusion, with higher levels persisting until 60 minutes after reperfusion. Cerebral ischemia was accompanied by cerebral edema early after reperfusion. The edema correlated with increased leukotriene C4 levels. That the increased brain water content was causally related to an increase in leukotriene C4 was supported by results obtained following administration of the 5-lipoxygenase inhibitors ONO-LP-016 and AA-861. Both inhibitors suppressed the increased leukotriene C4 and brain water contents after reperfusion. Our results indicate that leukotriene C4 is closely associated with an induction of ischemic cerebral edema.

6-Ketoprostaglandin F1 alpha↗

[Antitumoral effect of gamma-interferon in patients with hepatocellular carcinoma].

The antitumoral effect of gamma-Interferon (Re-IFN-gamma, KW-2202) on nine patients with hepatocellular carcinoma (HCC) has been investigated. gamma-IFN was administered intravenously biweekly at a dose of 8-24 x 10(6) units/day for 5 consecutive days. As all patients had measurable disease determined by an abdominal CT, the antitumoral effect was evaluated by CT, according to the criteria of Koyama and Saito, During gamma-IFN therapy, one patient, who received a total of 4.4 x 10(8) units of gamma-IFN, achieved a partial response (PR) 133 days after onset of treatment. Another patient showed a minor response (MR) 43 days after start of therapy. The duration of the PR and MR were 7.8 weeks and 10.8 weeks, respectively. Two patients were assessed as having had no change (NC), and 5 patients as still manifesting a progressive disease (PD). Marked falls in serum alpha-fetoprotein levels during therapy were observed in 2 cases of which one was graded as having obtained a PR, and the other, a NC. The toxicities observed were fever, general malaise, headaches, and joint pains, which were slight and transient in most cases. In one case, however, a therapy was stopped because of a continuous and severe shoulder pain with no metastasis. Further studies on the use of IFN, possibly in combination with other chemotherapeutic agents, should be performed in patients with HCC.

Aged↗