Search PubMed⌕ Search

Biomedical subjects

K Saeki

Publications and source records attributed to K Saeki.

At least 271 records · Page 15Linked to original sources
PubMed1989

Histamine turnover in the rat hypothalamic nuclei estimated from alpha-fluoromethylhistidine-induced histamine decrease.

The turnover rates, rate constants and half-life values of neuronal histamine (HA) in 10 nuclei of the rat hypothalamus were estimated from the depletion of HA induced by alpha-fluoromethylhistidine (alpha-FMH: 100 mg/kg, i.p.), a specific inhibitor of histidine decarboxylase, on the presumption that alpha-FMH depletable HA pools represent neuronal ones. Marked variation in the HA turnover rates were observed among the hypothalamic nuclei, ranging from 5.7 to 19.5 pmole/mg protein/hr.

Animals↗
PubMed1989

Spontaneous colon cancer and its spontaneous regression in highly inbred Wistar Furth rats: genetic analysis.

The incidence of spontaneously occurring colon cancer and its spontaneous regression in the highly inbred Wistar Furth (WF) rat was studied using 1346 rats from the 19th to the 21st inbreeding generation. A statistical analysis revealed a positive phenotypical correlation between parents and offspring concerning the incidence of colon cancer and its spontaneous regression. The incidences of cancer-bearing offspring born from the crosses of cancer-free dams and cancer-bearing, spontaneous regression and cancer-free sires were 21%, 14.1% and 22.7%, respectively, and these results manifested a statistically significant difference. The incidences of spontaneous regression in the male offspring born from the same crosses mentioned above were 35%, 46.8% and 23.5%, respectively; they also represented a significant difference. Based on the analysis, two independent genetic factors, one carcinogenic and the another regressive, were suggested to determine the phenotypes of offspring. The cancer-bearing offspring have the carcinogenic factor but not the regressive factor, while the spontaneous regression ones have both factors. The frequencies of the carcinogenic and the regressive factors in male rats were estimated to be 54.1% and 59.8%, respectively, on average from the 19th to the 21st generation. A genetic pool of the carcinogenic and the regressive factors was established in the WF rat.

Animals↗
PubMed1989

Morphology on spontaneous regression of the autochthonous colon carcinoma in WF Osaka rat strain.

In order to study the spontaneous regression of the colon cancers of WF Osaka strain rats, laparotomies were carried on 701 rats in sequence at the age of four months. Among them, 260 cases were found having colon cancers at the laparotomy. 107 out of them showed spontaneous regression of the colon cancer in the ascending colon. Most of the cases which spontaneously regressed were rather the early stage (stage 1 and 2) of the colon cancer, though 26 cases of advanced cancer also showed spontaneous regression. Grossly the lesions of the spontaneous regression were those of thickened, elongated ascending colon, with occasional dilation. Some cases showed the cystic formation at the portion of former lesions. There was a case which showed normal appearance of the ascending colon with regional lymph node metastasis measuring 1.5 x 1.5 centimeters. Histological appearance was varied showing reconstruction of the muscular layer and mucularis mucosae. Mucosal epithelium was almost normal looking, but glandular arrangement showed cystic dilation. The ectopic existence of glandular composition was seen in the restored lesion in the muscular layer. Macrophage infiltration was indispensably main histological reaction with central necrosis of formerly existed cancer cells, which was considered to be cellular immunity against cancer cells, or exogenous substances, such as viruses in cancer cells.

Animals↗
PubMed1989

[Comparative study on the anticancer activities of KW2149 and mitomycin C against human tumor xenografts using subrenal capsule assay].

The anticancer activity of KW2149, a new derivative of mitomycin C (MMC), was investigated against 5 human tumor xenografts derived from digestive organs using 4-day subrenal capsule assay (SRCA). Normal immunocompetent mice were used in this assay. For the comparative study, KW 2149 and MMC were administered intraperitoneally for 3 days after implantation, and the anticancer activity and the weight loss of mice were evaluated. The total doses were determined as 1/2, 1/3 and 1/4 of LD50 value of each anticancer agent. The anticancer activities of the two drugs were almost the same with no significant difference in 3 xenografts. Thus, it may be suggested the difference of the anticancer spectrum between the two drugs. The anticancer activity of KW2149 indicated higher correlation with the administered doses as compared with MMC. The toxicity of KW2149 was almost the same as MMC according to the weight loss of mice.

Animals↗
PubMed1989

[Combination chemotherapy of CPM-MTX-5-FU in non-resectable and recurrent cancer patients].

Fifty-two non-resectable and recurrent cancer patients with prior treatment, were entered in this study; 1 esophageal, 33 gastric, 1 duodenal, 4 colorectal, 2 pancreatic, 2 bile duct, and 9 breast cancer. The protocol of this therapy was as follows: On day 1, 500 mg/body cyclophosphamide (CPM) was administered by drip infusion, and on day 2, 200 mg/m2 methotrexate (MTX) was infused intravenously for 30 min; immediately after, 500 mg/body 5-fluorouracil (5-FU) was injected by bolus infusion for 5-10 min. On day 3, 24 hours after MTX administration, leucovorin rescue was added. This combination chemotherapy was repeated every two weeks. As a result, 35 of 52 patients were evaluable and the response rate (CR + PR) was investigated; 2/21 (9.5%) for gastric, 2/7 (28.6%) for breast, and 0% for miscellaneous. As complications for side effect, general fatigue, anorexia, nausea, vomiting and stomatitis were observed symptomatically, and leukopenia and thrombocytopenia were recognized in laboratory data as dose limiting factors.

Anorexia↗
PubMed1989

[Comparison of succinic dehydrogenase inhibition test with adenosine triphosphate inhibition assay for human solid tumors as in vitro chemosensitivity tests].

In order to determine the most effective anticancer agents for individual human tumor, succinic dehydrogenase inhibition test (SDI-T) and adenosine triphosphate inhibition assay (ATP-A) as in vitro chemosensitivity tests were performed. Fifty tumors and 57 tumors derived from cancer patients surgically methods were examined by SDI-T and ATP-A respectively. As the results, the evaluable rate was 70% by SDI-T and 94.7% by ATP-A, respectively. With SDI-T, the positive rate against all tumors was 51.4% in mitomycin-C (MMC), 42.9% in adriamycin (ADM), 20.0% in 5-fluorouracil (5-FU), 54.3% in cis-diamminedichloroplatinum (CDDP). On the other hand, with ATP-A, that was 20.4% in MMC, 29.5% in ADM, 20.6% in 5-FU, 20.4% in CDDP, respectively. Retrospective and prospective clinical trials were also carried out to determine the usefulness of both assays. With SDI-T, overall predictive accuracy rate was 57.1% while with ATP-A that was 88.9%. Furthermore, the rates of sensitivity for the same tumors using SDI-T and ATP-A were compared. The rate of the same sensitive cases in both assays were 30% with MMC, 70% with 5-FU, 42.1% with ADM, 36.8% with CDDP, respectively. In conclusion, it is suggested that ATP-A was more useful than SDI-T as in vitro chemosensitivity test to determine the most adequate drug for cancer patients.

Adenosine Triphosphate↗
PubMed1988

Histamine turnover in the brain of morphine-dependent mice.

The turnover of brain histamine was examined in mice implanted subcutaneously with a morphine pellet (50 mg free base). The numbers of naloxone-precipitated jumpings and body shakes were maximum 2 and 3 days after implantation, respectively. The brain tele-methylhistamine level significantly increased (50% to 115%) during 12 h-3 days after implantation of a morphine pellet, whereas the histamine level remained unchanged. The accumulation of tele-methylhistamine by pargyline treatment was significantly enhanced when pargyline was administered 12 h after implantation, suggesting an enhancement of histamine turnover. However, a similar degree of the tele-methylhistamine accumulation was induced by pargyline during 1-5 days after implantation, as compared with the accumulation in the control mice implanted with a placebo pellet. In mice undergoing morphine withdrawal by either the removal of morphine pellet or the treatment with naloxone 3 days after implantation, the degree of the pargyline-induced tele-methylhistamine accumulation or the (S)-alpha-fluoromethylhistidine (alpha-FMH)-induced histamine decrease was similar to that observed in the placebo pellet-control mice. The numbers of naloxone-precipitated jumpings and body shakes occurring in mice 3 days after implantation were not significantly affected by any of L-histidine, alpha-FMH or metoprine. These results suggest that turnover of histamine in the brain is enhanced by acute morphine treatment and returns to the normal rate in the stage of chronic treatment and remains unchanged during the state of withdrawal.

Animals↗
PubMed1988

Enhancement of blood-brain barrier permeability to sodium fluorescein by stimulation of mu opioid receptors in mice.

The effects of opioids on the permeability of the blood-brain barrier (BBB) were examined in mice with sodium fluorescein as an indicator of the permeability. The brain was perfused with saline 30 min after injection of sodium fluorescein (40 mg/kg, i.v.) and examined by fluorometry. Morphine hydrochloride (0.3-10 mg/kg, s.c.) markedly increased the brain level of sodium fluorescein dose-dependently without influencing the plasma level, when administered 20 min before sodium fluorescein injection. Intracerebroventricularly (i.c.v.) injected morphine hydrochloride (0.5 and 1.0 microgram) increased the brain sodium fluorescein level. Buprenorphine (0.1 and 0.5 mg/kg, s.c.) was also effective. However, pentazocine, ethylketazocine, U-50488H and SKF-10047 had no significant influence. The i.c.v. administration of [D-Ala2, MePhe4, Gly(ol)5]enkephalin (0.1 microgram) and [D-Ala2, D-Leu5]enkephalin (0.5 microgram) but not of [D-Thr2, Leu5]enkephalin-Thr increased the brain level of sodium fluorescein significantly. A small dose of naloxone (i.p.) significantly inhibited the effects of morphine, buprenorphine, [D-Ala2, MePhe4, Gly(ol)5]enkephalin and [D-Ala2, D-Leu5]enkephalin. ICI-174864 coadministered i.c.v. with [D-Ala2, D-Leu5]enkephalin was ineffective in antagonizing the effect of the latter. These findings suggest that the stimulation of mu opioid receptors results in an increase in BBB permeability to sodium fluorescein.

Animals↗
PubMed1988

Enhancement by alpha-fluoromethylhistidine of the thiopental sleep-prolonging action of delta 9-tetrahydrocannabinol.

The effect of alpha-fluoromethylhistidine (alpha-FMH), a specific inhibitor of histidine decarboxylase, on the potentiation of thiopental-induced sleep by delta 9-tetrahydrocannabinol (THC), which inhibits the histamine turnover in the brain, was examined in mice and rats. The sleeping time after injection of thiopental sodium (40 mg/kg, IV) was prolonged by THC (10 mg/kg, IP, 1 h before) to approximately twice the control value. alpha-FMH (50 mg/kg, IP) administered alone had no significant influence on the thiopental sleeping time. However, alpha-FMH given 1 or 3 h before THC treatment markedly enhanced the THC potentiation of thiopental-induced sleep. Such an enhancement by alpha-FMH was not observed when alpha-FMH was administered 15 h before THC treatment. The brain histamine level decreased by 60% during the first 4 h after alpha-FMH injection and remained low until 15 h after the treatment. The thiopental sleep-potentiating action of morphine, chlorpromazine and diazepam was not affected by pretreatment with alpha-FMH. The transient enhancing effect of alpha-FMH on the THC potentiation of thiopental-induced sleep suggests that the histaminergic system is one of the activating transmitter systems in the brain.

Animals↗
PubMed1988

Comparison of the size of neuronal and non-neuronal histamine pools in the brain of different rat strains.

The size of the neuronal and non-neuronal histamine pools in the brain of three different strains of rats was measured by assuming that the alpha-fluoromethylhistidine-induced maximal decrement of histamine represents the size of the neuronal pool. Although the total histamine levels in the brain showed a considerable interstrain variation, no significant interstrain difference was observed in the neuronal histamine level. These results suggest that the size of the neuronal histamine pool in the brain is relatively stable, whereas the size of the non-neuronal histamine pool is variable.

Animals↗
PubMed1988

The protein responsible for center A/B in spinach photosystem I: isolation with iron-sulfur cluster(s) and complete sequence analysis.

The 9 kDa polypeptide from spinach photosystem I (PS I) complex was isolated with iron-sulfur cluster(s) by an n-butanol extraction procedure under anaerobic conditions. The polypeptide was soluble in a saline solution and contained non-heme irons and inorganic sulfides. The absorption spectrum of this iron-sulfur protein was very similar to those of bacterial-type ferredoxins. The amino acid sequence of the polypeptide was determined by using a combination of gas-phase sequencer and conventional procedures. It was composed of 80 amino acid residues giving a molecular weight of 8,894, excluding iron and sulfur atoms. The sequence showed the typical distribution of cysteine residues found in bacterial-type ferredoxins and was highly homologous (91% homology) to that deduced from the chloroplast gene, frxA, of liverwort, Marchantia polymorpha. The 9 kDa polypeptide is considered to be the iron-sulfur protein responsible for the electron transfer reaction in PS I from center X to [2Fe-2S] ferredoxin, namely a polypeptide with center(s) A and/or B in PS I complex. It is noteworthy that the 9 kDa polypeptide was rather hydrophilic and a little basic in terms of the primary structure. A three-dimensional structure was simulated on the basis of the tertiary structure of Peptococcus aerogenes [8Fe-8S] ferredoxin, and the portions in the molecule probably involved in contacting membranes or other polypeptides were indicated. The phylogenetic implications of the structure of the present polypeptide as compared with those of several bacterial-type ferredoxins are discussed.

Amino Acid Sequence↗
PubMed1988

Pseudomonas stutzeri ferredoxin: close similarity to Azotobacter vinelandii and Pseudomonas ovalis ferredoxins.

The complete primary structure of Pseudomonas stutzeri strain ZoBell ferredoxin was determined by a combination of protease digestion, Edman degradation, and carboxypeptidase digestion and was: TFVVTDNCIKCKYTDCVEVCPVDCFYEGPNFLVIH PDECIDCALCEPECPAQAIFSEDEVPEDQQEFIELNADLAEVWPNITE KKDALADAEEWDGVKDKLQYLER. The calculated molecular weight was 12,110 excluding iron and sulfur atoms. The amino acid sequence was highly homologous to those of Azotobacter vinelandii and Pseudomonas ovalis ferredoxins. It showed, like the other two, a Tyr-Thr insertion between the second and third Cys, and extra Cys at position 24 and, compared to Clostridium- and Bacillus-type ferredoxins, an extended C-terminal sequence.

Amino Acid Sequence↗
PubMed1988

Galanin inhibits noradrenaline-induced accumulation of cyclic AMP in the rat cerebral cortex.

The effect of galanin on noradrenaline (NA)-induced accumulation of cyclic AMP was investigated in slices of rat cerebral cortex. NA (10(-4)M) increased cyclic AMP levels during a 20-min observation period. Galanin (3 X 10(-7)M) significantly inhibited this response at all time points examined, although it did not change the basal levels of cyclic AMP. Galanin (10(-8)-3 X 10(-6)M) inhibited the cyclic AMP response to NA (10(-4)M) in a dose-dependent manner, with an IC50 of approximately 5.6 X 10(-8)M and a maximum inhibition of 59%. These results suggest that galanin, devoid of any detectable effects by itself, modulates the cyclic AMP response to NA in the rat cerebral cortex.

Animals↗