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Biomedical subjects

S Nagahama

Publications and source records attributed to S Nagahama.

At least 19 recordsLinked to original sources
PubMed2001

Synchronized propagation mechanism for crystalline-state polymerization of p-xylylenediammonium disorbate.

We describe the results of the topochemical polymerization of p-xylylenediammonium disorbate as the bifunctional monomer in the crystalline state via a radical chain polymerization mechanism. The structure and properties of the resulting double-stranded polymer are investigated by X-ray crystal structure and thermal analyses as well as IR spectroscopy. The stereochemical structure of the polymer is confirmed by NMR spectroscopy after the solid-state transformation of the polymer side chain to give the single-stranded chains that are soluble in methanol. We propose a model for the reaction mechanism to provide a ladder polymer in the crystalline state on the basis of the results of single-crystal structure analysis and the observation of the alpha-methyl and alpha-carboxylate propagating radicals by ESR spectroscopy. The two reaction parts of the monomer are synchronized to simultaneously react with the conformational change in a sorbate moiety that is transformed into another sorbate through the diammonium part as the linker.

Journal Article↗
PubMed2001

Chemotaxonomy on the leaf constituents of Thujopsis dolabrata Sieb. et Zucc.-Analysis of neutral extracts (diterpene hydrocarbon).

The leaf terpenes in Thujopsis dolabrata from all regions in Japan were analyzed using GC and GC-MS. The results show that the major constituents of the diterpene hydrocarbon fraction in this conifer are dolabradiene, hibaene, rimuene, 13-epi-dolabradiene and abietatriene. There were wide variations in the contents of the constituents among individuals and habitats. The results also show that T. dolabrata trees from 34 habitats can be classified into three groups based on the composition of the leaf diterpene hydrocarbon.

Journal Article↗
PubMed2000

Straight-chain fatty alcohols in the hyperthermophilic archaeon Pyrococcus furiosus.

Two straight-chain fatty alcohols (n-hexadecanol and n-octadecanol) were found in the neutral lipid fraction extracted from Pyrococcus furiosus cells. They were identified by thin-layer and gas-liquid chromatography, mass and infrared spectra, and chemical modification. The fatty alcohols accounted for 54% of the neutral lipid of the cell.

Chromatography, Thin Layer↗
PubMed1999

DNA ploidy, Ki-67 and p53 as indicators of lymph node metastasis in early gastric carcinoma.

OBJECTIVE: To perform flow cytometric and immunohistochemical analysis of early gastric carcinoma in order to investigate the clinical value of DNA ploidy, Ki-67 and p53 as indicators of lymph node metastasis. STUDY DESIGN: We studied 108 cases of surgically resected early gastric carcinoma, which comprised 21 cases showing positive lymph node metastasis (group A) and 87 cases showing negative lymph node metastasis (group B). RESULTS: Aneuploidy was seen in 16 cases (76.2%) in group A in contrast to 10 cases (11.5%) in group B (P = .0029). The mean value of the Ki-67 labeling rate in all cases was 21.9%, and 15 cases (79.0%) showed a Ki-67 labeling rate of more than 21.9% in group A, while they numbered 31 (37.4%) in group B (P = .0016). Cases with cell positive for p53 protein numbered 15 (75%) in group A, while they numbered 38 (46%) in group B (P = .0460). CONCLUSION: DNA aneuploidy, a high labeling rate of Ki-67 and overexpression of p53 are all useful indicators of lymph node metastasis in patients with early gastric carcinoma.

Aneuploidy↗
PubMed1998

[Serum carcinoembryonic antigen doubling time in patients with recurrent gastrointestinal carcinoma and its relationship to tumor biology and life expectancy].

BACKGROUND: The present study was done to determine if carcinoembryonic antigen (CEA) concentration doubling time can predict the course of disease in patients with adenocarcinoma of the gastrointestinal tract and characterize tumor biology. METHODS: CEA doubling times were determined from semilogarithmic plots of CEA concentration time courses in 20 patients with recurrent gastric cancer and 17 with recurrent colorectal cancer. RESULTS: Gastric and colorectal carcinomas showed mean CEA doubling times of 229 days and 85 days, respectively. There were no significant differences with regard to patient age, tumor size, gross appearance and histological differentiation. However, women had shorter CEA doubling times than did men. Flow cytometric analysis showed that tumors with a higher proportion of cells in S-phase (> or = 15%) had significantly shorter CEA doubling times than those with a lower S-phase fraction (< 15%). There was a significant correlation between the CEA doubling time and the length of survival after the initial CEA concentration increase in patients with recurrent gastric and colorectal carcinomas. CONCLUSIONS: CEA doubling time predicts life expectancy in patients with adenocarcinoma of the gastrointestinal tract. Differences in survival time are closely associated with variations in the biological aggressiveness of individual tumors.

Aged↗
PubMed1998

Determination of the active moiety of BX661A, a new therapeutic agent for ulcerative colitis, by studying its therapeutic effects on ulcerative colitis induced by dextran sulfate sodium in rats.

5-[4-(2-Carboxyethylcarbamoyl)phenylazo]salicylic acid disodium salt dihydrate (CAS 80573-04-2, BX661A) is being developed as a therapeutic drug for ulcerative colitis. To determine the active therapeutic moiety of BX661A, the therapeutic effects with single and combined administration of 5-aminosalicylic acid (5-ASA), 4-aminobenzoyl-beta-alanine (4-ABA) and 4-amino-N-2-pyridinyl-benzenesulfonamide (CAS 144-83-2, sulfapyridine, SP) on ulcerative colitis induced by dextran sulfate sodium (DSS) in rats were investigated, and the following results were obtained. 1. BX661A at doses of 30, 100 and 300 mg/kg (p.o.) dose-dependently decreased the erosion area (mm2) in the large intestine with % inhibition values of 28.7, 49.1 and 61.6%, and the shortening of the large intestine with % inhibition values of 17.1, 25.7 and 48.6%, respectively. Salazosulfapyridine (SASP) at doses of 30 and 100 mg/kg (p.o.) decreased the erosion area (mm2) in the large intestine with % inhibition values of 30.7 and 45.3%, respectively, but did not improve the shortening of the large intestine. However, at a dose of 300 mg/kg (p.o.) SASP, the % inhibition value of the erosion area in the large intestine was reduced. 2. A single intrarectal administration of 5-ASA (105 mg/kg, i.r.) significantly decreased the erosion area (mm2) in the large intestine, but a single administration of 4-ABA or SP did not show any significant effect on the erosion area. Combined administration with 5-ASA (105 mg/kg, i.r.) and 4-ABA (142.8 mg/kg, i.r.) significantly decreased the erosion area (mm2) in the large intestine with a % inhibition value of 63.8%. On the other hand, the efficacy of 5-ASA disappeared with combined administration with SP (% inhibition value of 7.3%). These results suggest that 5-ASA is the active moiety for the therapeutic effects of BX661A and indicate that the efficacy of 5-ASA disappears with the combined use of SP, but not of 4-ABA. Therefore, it seems that BX661A is clinically safe and more effective than SASP in the treatment of patients with ulcerative colitis.

Alanine↗
PubMed1997

[Pharmacological studies of BX661A. 5-[4-(2-carboxyethylcarbamoyl)-phenylazo]-salicylic acid disodium salt dihydrate (1). Therapeutic effects on dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) model in rats].

In the present study, we investigated the therapeutic effects of 7- or 14-day treatment with BX661A or salazosulfapyridine (SASP) in the DSS-induced UC model in rats. BX661A (10-300 mg/kg, p.o.) dose-dependently decreased the erosion area and the shortening of the large intestine. On the other hand, SASP (30 and 100.mg/kg, p.o.) dose-dependently decreased the erosion area in the treatment for 14 days (on the contrary, % inhibition of erosion area was reduced by the dose of 300 mg/kg), but did not improve the shortening of the large intestine. Secondly, we investigated the therapeutic effects of 5-aminosalicylic acid (5-ASA), 4-aminobenzoyl- beta-alanine (4-ABA) and sulfapyridine (SP) by intrarectal administration on the DSS-induced UC model in rats. 5-ASA significantly decreased the erosion area in the large intestine and improved the length of the large intestine of rats that was shortened by ingesting DSS. On the other hand, 4-ABA and SP improved neither the shortening nor the erosion area of the large intestine. These results suggest that BX661A may be clinically effective and useful in the treatment of patients with ulcerative colitis. Furthermore, it was suggested that 5-ASA may be the active moiety for the therapeutic effects of BX661A and SASP.

Administration, Oral↗
PubMed1997

[Analysis of DNA ploidy pattern and overexpression of p53 protein in cases of early gastric carcinoma with lymph node metastasis].

Twenty-one cases of surgically resected early gastric carcinoma with lymph nodal involvement (4 mucosal and 17 submucosal carcinomas) and 37 cases of that with no lymph nodal involvement (14 mucosal and 23 submucosal) were investigated by means of flow cytometry and immunohistochemical staining in order to clarify the correlation between lymph node metastasis and DNA ploidy pattern as well as overexpression of p53 protein. DNA aneuploidy was found to show a significantly higher frequency in submucosal carcinomas (60.0%) than in mucosal ones (22.2%), and also a significantly higher frequency in node positive cases (76.2%) than in node negative ones (32.4%). Meanwhile, the overexpression of p53 protein showed higher frequency in submucosal carcinomas (52.5%) than in mucosal ones (22.2%), and also higher frequency in node positive cases (47.6%) compared with that in node negative ones (40.5%). However there was no significant difference either in relation to the depth of tumor invasion or the lymph node metastasis. Thus, DNA aneuploidy showed a significant correlation to the depth of cancer invasion as well as lymph node metastasis, which was regarded as a useful indicator for the preoperative estimation of the depth of tumor invasion as well as lymph node metastasis.

Aneuploidy↗
PubMed1996

[Study on the experimental ulcerative colitis (UC) model induced by dextran sulfate sodium (DSS) in rats (3)].

We have already confirmed that symptoms in the experimental UC model in rats induced by ingesting DSS resembled those of human UC. In the present study, to clarify the participation of chemical mediators concerned with the development and etiology of the experimental UC model, we investigated the effects of superoxide dismutase (SOD), 5-aminosalicylic acid (5-ASA), AA-861, an LTB4-receptor antagonist (LTB4-ra), indomethacin (Ind) and OKY-046 on the DSS-induced UC model in rats. The UC model was produced by giving rats drinking water containing 3% DSS, and animals were selected when bloody stool was observed in more than 90% of the animals. After selection, drugs were intrarectally administered once a day, for 7 days, to UC rats that were given drinking water containing 1% DSS. SOD, 5-ASA, AA-861 and LTB4-ra inhibited the formation of erosions in the large intestine. Furthermore, SOD, 5-ASA and LTB4-ra improved the length of the large intestine of rats that had been shortened by ingesting DSS. On the other hand, neither Ind nor OKY-046 improved the shortening and erosion of the large intestine. From these results, it is concluded that the free radical and lipoxygenase metabolites of arachidonic acid may be partially involved in the DSS-induced UC model in rats.

Aminosalicylic Acids↗
PubMed1996

[Correlation between intratumor DNA ploidy distribution pattern and prognosis by tumor stage in colorectal carcinomas].

Curatively resected specimens of 124 cases of colorectal carcinoma, and 6 cases of colorectal carcinoma showing hematogenous metastasis were used in this study. Each carcinoma was cut out in stepwise section through the entire tumor. DNA ploidy for each section was determined by flow cytometry, and the intratumor DNA ploidy distribution pattern was decided, and divided into 5 types (Type A-E). These 5 types were broadly divided into 2 types; predominantly diploidy type (Type A, C) and predominantly aneuploidy type (Type B, D, E). A statistically significant difference was seen in the 5-year survival between 25 cases of the predominantly diploidy type (100%) and 99 cases of the predominantly aneuploidy type (76.7%). However, there was no statistically significant difference in survival between these 2 types in any Dukes stage. The intratumor DNA ploidy distribution pattern in 6 cases of colorectal carcinoma showing hematogenous metastasis comprised 3 cases of Type E, 2 Type D and 1 Type B. And that of 8 cases of curatively resected colorectal carcinoma showing hematogenous metastasis postoperatively comprised 5 cases of Type D, 2 Type E and 1 Type B. Thus, a close correlation between the aneuploidy predominant type, especially Type D as well as Type E, and hematogenous metastasis, was suggested.

Colorectal Neoplasms↗
PubMed1996

[Correlation between intratumor DNA ploidy distribution pattern and clinicopathologic variables in large-bowel carcinoma].

Surgically resected specimens of 139 cases of large-bowel carcinoma were analysed in this study. Each carcinoma was cut out in stepwise section through the whole tumor, and flow cytometric DNA measurement was performed for each section. The intratumor DNA ploidy distribution pattern decided in this way was classified into 5 types (Type A-E). The 139 cases of carcinoma comprised 19 cases of Type A, 27 Type B, 11 Type C, 37 Type D and 45 Type E. The intratumor DNA ploidy distribution pattern showed a statistically significant correlation to tumor size, gross type, depth of invasion, growth pattern at the tumor margin, venous permeation of visceral wall, DNA Index and Dukes stage. Among these 5 types of carcinoma, carcinoma showing Type E was seen most frequently, even in the earlier stage, and found most frequently among the cases showing invasive growth pattern at the tumor margin, positive venous permeation in the visceral wall and DNA Index of more than 1.7. Therefore, the intratumor DNA ploidy distribution pattern seemed to reflect the degree of tumor malignancy as well as that of tumor advancement. Moreover, Type E pattern of carcinoma appeared to reveal the highest grade of malignancy, and early detection of this type seemed to be necessary in order to improve survival after surgery.

Colonic Neoplasms↗
PubMed1995

[Study on the experimental ulcerative colitis (UC) model induced by dextran sulfate sodium (DSS) in rats (2)].

We have confirmed that symptoms in the experimental UC model in rats induced by ingesting 3% DSS were similar to those of the human UC. In this study, we investigated the procedure for assessing the therapeutic effect of SASP and PSL. (1) The UC model was produced by giving rats drinking water containing 3% DSS, and animals were selected when bloody stool was observed in more than 90% of the animals. (2) Procedure for selection of rats: (a) presence of bloody stool for more than two consecutive days, (b) concentration of hemoglobin at more than 10 g/dl and (c) B.W. on the day of selection was not decreased more than 20 g against the B.W. on the day before the selection. (3) After selection, various concentrations of DSS (1-3%) were given to rats for 14 days. SASP and PSL were administered to the UC model once a day for 14 and 7 days, respectively, with the animals given drinking water containing 1% DSS after the selection. SASP (100 mg/kg, p.o.) and PSL (1 mg/kg, i.r.) significantly inhibited the formation of erosion by 56.1 and 47.5%, respectively. In conclusion, this procedure used herein seems to be useful for assessing the therapeutic effect of a drug for human UC.

Animals↗
PubMed1994

Reconstitution of the isobutene-forming reaction catalyzed by cytochrome P450 and P450 reductase from Rhodotorula minuta: decarboxylation with the formation of isobutene.

An isobutene-forming activity was reconstituted with cytochrome P450rm and cytochrome P450 reductase purified from Rhodotorula minuta. The nonionic detergent. Emulgen 911, present in the preparation of purified P450rm, inhibited the reconstitution. Bovine serum albumin enhanced the activity of the reconstituted system. Branching of the beta carbon of the substrate carboxylic acid was important for formation of isobutene. In a comparative study with isovalerate and 3-deuterio-3-methylbutanoate, a very large isotopic effect (kH/kD = 14) was observed. This result indicates that formation of isobutene might be initiated by abstraction of hydrogen from the beta carbon of isovalerate and might be followed by decarboxylation.

Alkenes↗
PubMed1993

[Study on the experimental ulcerative colitis model induced by dextran sulfate sodium in rats: estimation of mucosal erosions by the alcian blue-staining method].

We have developed a new method that is applicable for a macroscopic and objective evaluation of erosion in the large intestine in the experimental ulcerative colitis model induced by dextran sulfate sodium (DSS) in rats. The large intestine (without cecum) fixed in 10% neutral buffered formalin solution for more than one week was opened and stained with 1% alcian blue solution. The mucosal surface was stained in light and shade-blue. Histopathological examination revealed that the dark blue area on the mucosal surface had no epithelia and that the connective tissues in the lamina propria were stained with alcian blue. Salazosulfapyridine at 15 and 50 mg/kg twice a day inhibited the erosion area (dark blue area) by 29.6% and 50.2%, respectively. Also, prednisolone at 0.5 mg/kg, twice a day inhibited the erosion by 53.3%. Thus, by measuring the dark blue area stained with 1% alcian blue solution, we could estimate macroscopically and objectively the area of erosions. This method seems to be a useful index for assessing the damages produced in the experimental ulcerative colitis model in rats.

Alcian Blue↗
PubMed1991

Intrasellar cavernous angioma in neurofibromatosis.

A case of neurofibromatosis complicated by a large intrasellar (pituitary) cavernous angioma is reported. Vascular abnormalities, consisting of smooth muscle cell proliferation in the intima of the intermediate and small arteries, were also observed in branches of the renal and pulmonary arteries. An association between neurofibromatosis and intracranial cavernous angioma is discussed.

Autopsy↗
PubMed1988

Blunted pressor responsiveness to quinpirole, a specific dopamine D2 receptor agonist, in conscious deoxycorticosterone acetate/NaCl hypertensive rats is related to atrial natriuretic peptide release.

Our previous studies have demonstrated: 1) that i.v. quinpirole (LY171555), a selective dopamine D2 receptor agonist, has a dose-dependent pressor effect in conscious rats which is mediated by activation of sympathetic outflow and vasopressinergic activity, and 2) that the activity of central dopaminergic neurons is reduced in deoxycorticosterone acetate (DOCA)/NaCl hypertensive rats. To elucidate the role of central and peripheral dopaminergic systems in the pathogenesis of DOCA/NaCl hypertension, we examined the effects of quinpirole on mean arterial pressure, heart rate, plasma norepinephrine, epinephrine, arginine vasopressin and atrial natriuretic peptide (ANP) in conscious 4-week-old DOCA/NaCl hypertensive and normotensive control rats. Quinpirole (1 mg/kg i.v.) increased mean arterial pressure in both groups, but the pressor response was attenuated in DOCA/NaCl rats. Paradoxically, quinpirole-induced increments in plasma norepinephrine, epinephrine and arginine vasopressin were greater in DOCA/NaCl rats. In addition, quinpirole induced a 2-fold increase in plasma ANP (P less than .01) in both DOCA/NaCl and control rats. Pretreatment with domperidone (2.5 mg/kg i.v.), a peripherally acting dopamine D2 antagonist, enhanced the maximum pressor response to quinpirole in both groups, restored the quinpirole-induced pressor response to control levels in the DOCA/NaCl rats and blocked the stimulatory effect of quinpirole on ANP release in both groups. These data indicate that peripheral dopamine D2 receptors modulate ANP secretion in the rat. The observation that the quinpirole-induced increment in plasma ANP was enhanced in DOCA/NaCl rats supports the hypothesis that the blunted pressor response to quinpirole in this model is related to enhanced ANP release.

Animals↗
PubMed1987

Yohimbine-induced alterations of monoamine metabolism in the spontaneously hypertensive rat of the Okamoto strain (SHR). II. The central nervous system (CNS).

Steady state levels of monoamine neurotransmitters were examined in SHR, a genetic model of hypertension and compared to its normotensive control (WKY). SHR and WKY were also challenged with alpha 2-adrenergic antagonists, (yohimbine, YOH, idazoxan) or an alpha 1-antagonist (prazosin) and alterations in CNS monoamine metabolism evaluated. SHR were found to have elevated levels of NE and 5-HT in a number of brain regions involved in cardiovascular control when compared to WKY. DA levels and metabolism were also altered in the SHR. Blockade of alpha 2-adrenoceptors and other direct and indirect actions of YOH exacerbated the abnormalities in central monoaminergic neurotransmission in SHR. Significant decreases in NE content were produced by YOH or idazoxan treatment in both SHR and WKY, presumably the result of the inhibition of alpha 2-adrenoceptor medicated presynaptic control of NE release. YOH treatment abolished the differences in steady state levels of NE between SHR and WKY, however, idazoxan did not. YOH administration resulted in significant increases in DA and 5-HT in a number of brain regions of both SHR and WKY. Idazoxan or prazosin produced few changes in DA and 5-HT metabolism except for increases in DA content in the spinal cord and brainstem of SHR given idazoxan. The YOH-induced increases in DA and 5-HT content of SHR were of a greater magnitude than the WKY in several brain regions. DOPAC levels were significantly elevated by YOH in both WKY and SHR, reflecting the antidopaminergic properties of YOH. 5-HIAA content was significantly reduced by YOH in a number of brain regions in both SHR and WKY, however, this effect was attenuated in several brain regions in SHR. The results of the present study demonstrate the multifarious nature of the alterations in CNS monoamine metabolism in SHR.

Animals↗