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Biomedical subjects

H Kamei

Publications and source records attributed to H Kamei.

At least 163 records · Page 9Linked to original sources

[Phase I study of bestrabucil (KM 2210)].

A phase I study was performed on a newly developed antitumor agent, Bestrabucil (KM 2210). The study was started at an initial dose of 1 n 25 mg/body, and gradually increased up to 32n 800 mg/body. With single (35 patients) and five-consecutive-day (36 patients) administration, the dose-limiting factor was found to be tarry stool, remarkable decrease in hemoglobin content, and strong nipple and breast pain. The maximum tolerated dose (MTD) was concluded to be around 700 to 800 mg/body. With long-term administration (the longest term, 20 weeks, 36 patients), the dose-limiting factor was concluded to be a decrease in the peripheral leukocyte count when the total amount administered reached about 10 g. Side effects on the alimentary system due to this agent, such as vomiting, nausea and anorexia, were observed. In addition, mastalgia and genital bleeding due to released estrogen were also seen, especially in the case of long-term administration.

Adult↗

Functional alteration of opioid receptor subtypes in the mice exhibited conditioned suppression in motility.

Mice exhibit a marked suppression of motility (conditioned suppression) when placed in the same environment in which they had previously received the electric footshock. The present study was designed to investigate the functional change of opioid receptor subtypes in the conditioned suppression group using an opioid binding assay technique. In the synaptic membrane of the conditioned suppression group, the binding capacities of [3H]naloxone at high and low affinity binding sites and of [3H]phencyclidine at high affinity binding site were significantly increased compared to those of the control group. On the other hand, the binding capacity of [3H]ethylketocyclazocine at both affinity binding sites in the conditioned suppression group was not changed. These results suggest that the binding function of different opioid receptor subtypes may be altered differently by stress.

Animals↗

Electric footshock-induced changes in behavior and opioid receptor function.

The present electric shock (ES) schedule produced significant behavioral changes, such as analgesia and motor suppression, and functional changes in binding capacities for opioid agonist and antagonist. In the naloxone (5 mg/kg, SC 15 min before ES application) pretreated rats, these behavioral and biochemical changes were blocked. In addition, when preincubation (37 degrees C, 30 min) was not carried out in the process of preparation of synaptic membrane, the ES-induced functional changes in hibh affinity binding sites were not observed. Moreover, the present data indicated that preincubation may produce the destruction of [3H]-D-ala2,L-met5-enkephalinamide ([3H]-DAMEA) specific binding sites with the forced dissociation of endogenous delta-type opioid peptides from delta opioid receptors. In addition, the significant decrease of [3H]-DAMEA specific binding in the ES membrane suggested that delta-type opioid peptides were released more than steady state level by ES application and bound to the delta opioid receptors. Therefore, these results suggest that ES-induced behavioral and biochemical changes were mediated by opioid peptides which were released by ES application. In addition, the ES-induced analgesia may be mediated by high affinity delta opioid receptor.

Analgesia↗

Mononuclear phagocyte colony formation of human spleen cells in liquid culture.

We found that mononuclear phagocytes formed a distinct number of clusters and colonies on the bottom of a culture dish 7 days later but granulocytes did not, when a large number of human spleen cells were cultured in liquid medium. In all gastric cancer bearers and patients with portal hypertension operated on, however, colony formation was restricted to spleen cells from patients with advanced gastric cancer and from a group of patients with portal hypertension. These spleen cells formed mononuclear phagocyte colonies without the help of exogeneous colony stimulating factor (CSF). We further demonstrated that the colony-forming cells were glass non-adherent and nylon wool adherent, and that spontaneous colony formation required cooperation between the colony-forming cells and colony-stimulating cells adherent to a plastic surface.

Cell Adhesion↗

The interaction of eptazocine, a novel analgesic, with opioid receptors.

The profile of action of eptazocine, a novel analgesic, on opioid receptors was investigated. Eptazocine caused a concentration-dependent inhibition against the [3H]-naloxone [( 3H]-NLX) specific binding to rat brain synaptic membrane in the absence of sodium cation and GTP (IC50; 7.83 +/- 1.57 microM). The ratios of IC50 values between the absence to the presence of sodium cation alone or sodium cation and GTP were 3.89 and 4.35, respectively. In addition, eptazocine (10 microM) also produced the significant decrease of [3H]-NLX specific binding in the mouse brain synaptic membrane. Moreover, the same dose eptazocine significantly decreased the [3H]-ethylketocyclazocine [( 3H]EKC) specific binding, but not [3H]-phencyclidine [( 3H]-PCP). These results suggest that eptazocine interacts with opioid receptor, and is classified as one of the opiate agonist-antagonist analgesics.

Analgesics↗

[Ogilvie's syndrome--a case report and review].

Ogilvie's syndrome is caused from functional obstruction of the colon without mechanical stenosis and also termed as pseudo-obstruction of the colon. This disease is seen in patient who has other causative distress. The pathogenesis of this rare entity is unknown but it is suspected that there may be an underlying autonomic disturbance which causes non-mechanical obstruction of the colon. Most of the case reports on Ogilvie's syndrome have appeared in European and North American journals but are extremely rare in Japan. Some cases which have been categorized "spastic ileus" may be included in this syndrome. We recently experienced a patient with cerebral infarction who developed non-mechanical obstruction of the colon. This patient was treated successfully with an exploratory laparotomy and sigmoidostomy. It is considered that early diagnosis is an essential part of the initial management of this syndrome. Conservative treatment is indicated for most of the patients but a definitive surgical therapy is occasionally necessary.

Aged↗

[Proliferation of scirrhous type of gastric carcinoma and its treatment].

An attempt was made to clarify the clinical prognosis of scirrhous type of gastric carcinoma and to improve its treatment. The cases of gastric carcinoma operated and histologically well analyzed from 1969 to 1973 was 178, and scirrhous type was included in 52%. Advanced carcinoma (more than ss alpha) was 80% in scirrhous type and 40% in non-scirrhous type. Five year survival rate in scirrhous type was 45% and 59% in non-scirrhous type. (P divided by 0.09). In pm carcinoma, however, the 5 year survival rate of scirrhous type was higher than that of non-scirrhous type (P divided by 0.06). Between the primary lesions and lymphatic metastasis, histologic type was not the same in 70%. The survival rate of scirrhous type in lymphatic metastasis was again higher than that of the non-scirrhous type. Mitotic index was 18.6 +/- 8.6 in scirrhous type, 52.8 +/- 13.5 in medullary type, 54.1 +/- 16.5 in intermediate type and 53.3 +/- 11.5 in non-cancerous gastric epithelium. For the scirrhous type with a large amount of highly degenerated interstitial and poor blood vessel supplying, many doses of chemotherapeutic agents may be necessary, and, especially, cytostatic agents should be administered for long periods.

Adenocarcinoma, Scirrhous↗

[Cooperative studies on surgical adjuvant immunochemotherapy for prevention of postoperative recurrence of gastric cancer].

A controlled clinical trial of surgical adjuvant immunochemotherapy of gastric cancer was started in July, 1974 involving twelve institutes (Chairman; T. Kondo) in Japan. Patients with gastric cancer undergone curative resection were eligible. These patients were divided into 3 groups; Group A, mitomycin C (MMC) + 5-fluorouracil (5-FU): Group B, MMC + 5-FU + PSK or MMC + 5-FU + OK-432; and Group C, surgery alone. Of 1412 patients accumulated up to December 1977, 848 cases were evaluable: Group A-264 cases, group B-290 and group C-294. Side effects such as leukopenia, thrombopenia, elevated GOT and GPT, albuminuria and digestive disorders, were observed in 54 cases (20.5%) of group A and in 59 cases (20.3%) of group B. The 3-year survival rates of total cases were 79.2% with group A, 77.0% with group B and 85.2% with group C. The 2-year survival rates of histological stage II cases were 93.4% with group A, 90.5% with group B and 80.7% with group C. The difference in survival rate between A and C (12.7%) was statistically significant (p less than 0.05). The efficacy was not related to the histological type of gastric cancer. Adjuvant immunochemotherapy using OK-432 was significantly effective on a 1-year survival rate of stage IV gastric cancer.

Adult↗

[Leukocyte migration inhibition (LMI) of murine spleen cells after immunization with tumor cells, and an experimental study with LMI in combination therapy with a non-specific immunostimulant and a chemotherapeutic agent].

We have previously reported the leukocyte migration inhibition (LMI) factor in cancer patients, which is one of the specific parameters of cell mediated immunity. Since interpretation of these results was sometimes difficult in human cancer because of the unknown participation in the reaction, the inbred mouse strains were used as an experimental animal. We studied how the LMI factor of murine spleen cells changed with immunization of tumor cells, and intraperitoneal injection of protein polysaccharide (PSK) and/or cyclophosphamide (CPA). Method. LMI was performed by Clausen's method. Mouse strain; C3H/Heston. Tumors; C3M2 (methylcholanthrene induced tumor) and MAC (spontaneous mammary tumor). Result. Migration cells of murine spleen cells were almost granulocytes. Migration inhibition was maximum in 2 to 3 weeks after immunization of tumor cells. In vivo studies as well as in vitro studies revealed that C3M2 and MAC were not crossreactive. Migration was accelerated with CPA and inhibited with PSK. Leukocyte migration was inhibited by injection of PSK after treatment of CPA at a dose of 50 mg/kg, while in the case of CPA at a dose of 200 mg/kg, preinjection of PSK inhibited leukocyte migration.

Adjuvants, Immunologic↗

[Using CEA for diagnostic, therapeutic and prognostic evaluation in colorectal cancers].

Serum CEA measured by radioimmunoassay was studied in 63 colorectal cancer patients. The present study was designed to assess the usefulness of serum CEA assay on the diagnosis of colorectal cancer at various stages and in the care of prognosis. CEA was examined before and after surgery at appropriate intervals. Serum CEA test was positive (over 2.5 ng/ml) in 10.5% of the 19 patients with Dukes stage A, in 61.9% of 21 patients with Dukes stage B, and in 78.3% of 23 patients with Dukes stage C. Curative resection was able to perform in all of colorectal cancer patients with values of less than 2.5 ng/ml, in 75% of them with values of 2.5-10 ng/ml and in 45% of them with values of greater than 10 ng/ml. High serum CEA levels decreased to normal levels within 1-3 months after curative resection. High CEA levels were observed before the secondary operation in 4 out of 5 patients who underwent reoperation because of the evidence of recurrence. CEA decreased to normal levels in 3 of them and increased to 500 ng/ml in 1 case. In the last case CEA sustained high levels until the death due to metastasis to the lung and lymph nodes.

Carcinoembryonic Antigen↗

Effect of retinoic acid on cell-cell adhesiveness in cloned BHK21/C13 cells which form piling-up colonies.

The effect was studied of retinoic acid (RA) on cell-cell adhesiveness in Ag8-1 cells, which are piling-up colony-forming cells cloned from a Syrian hamster kidney fibroblastic cell line BHK21/C13. From the piled-up part of the colonies grown with RA (10 microM), many cells were dissociated by mere shaking or pipetting. The dissociated cells soon adhered to and spread on plastic surfaces in the presence of RA. The number of cells per colony increased almost at the same rate in the presence or absence of RA. The effect of RA on the appearance of cells dissociable from colonies was noticeable above 0.1 microM, prominent from 1 to 10 microM, greater when added in the earlier stages of colony formation and negligible when added just before the dissociation assay. Single cells from the monolayer culture grown with RA (10 microM) had less tendency to aggregate than did those from the control culture. Cells from the colonies grown with RA adhered to and spread on a plastic dish for bacterial use, but control cells seldom adhered. These results indicate that RA decreases the cell-cell adhesiveness or suppresses the development of it but increases cell-substratum adhesiveness.

Animals↗

[Experimental study on the action mechanism of a new bronchodilator agent, BB-1502].

The action mechanism of the bronchodilator activity of BB-1502 was studied in comparison with aminophylline. Orally administered BB-1502 did not inhibit passive cutaneous anaphylaxis in rats, an immediate allergic reaction of Type I, but strongly protected the same antigen-mediated anaphylactic asthma by the intraduodenal route, the activity being approximately 13 times more potent than that of aminophylline. BB-1502 also inhibited IgG-mediated anaphylactic asthma in guinea pigs by the oral route. Both IgE- and IgG-mediated histamine releases from rat lung were similarly inhibited by BB-1502, the potency being 2--3 times that of aminophylline. Disodium cromoglycate showed specific inhibition of the IgE-mediated reaction. BB-1502 and aminophylline showed nonspecific inhibition of the spasms of guinea pig ileum elicited by histamine, acetylcholine and BaCl2. Both compounds inhibited cyclic AMP and cyclic GMP phosphodiesterases (PDEs) derived from guinea pig organs. BB-1502 specifically inhibited the cyclic AMP PDE of lung and brain origins, while aminophylline showed no such specificity. The results of the present study suggested that the bronchodilator and anti-asthmatic actions of BB-1502 might, at least in part, be due to the regulation of cyclic nucleotide PDEs.

3',5'-Cyclic-AMP Phosphodiesterases↗