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Biomedical subjects

S Okabe

Publications and source records attributed to S Okabe.

At least 55 records · Page 3Linked to original sources
PubMed2001

Inhibition of concanavalin A-induced mice hepatitis by coumarin derivatives.

The effects of coumarin derivatives, osthole, imperatorin, Pd-Ia, Pd-II and Pd-III, on mice concanavalin A (Con A) (0.2 mg/mouse, i.v.)-induced hepatitis were studied. At the dose of 200 mg/kg (i.p.), these coumarins inhibited more than 90% of the Con A-induced elevation of plasma alanine aminotransferase activity, but glycyrrhizin (200 mg/kg, i.p.) caused only 45% inhibition. At the dose of 100 mg/kg (i.p.), osthole produced the strongest inhibition among these coumarins. The inhibitory activity of osthole is lost when its 7-methoxy group is replaced by a 7-hydroxy group to form osthenol. The present results showed that coumarin derivatives inhibited Con A-induced hepatitis, with osthole being the most inhibitory.

Alanine Transaminase↗
PubMed2001

MALT lymphoma originating in breast and uvula.

A case of marginal zone B cell lymphoma of MALT type arising in the uvula and breast is reported. The patient, a 30-year-old woman who delivered a child and lactated in 1997, was suffering from Sjögren syndrome (SS). She was diagnosed with MALT lymphoma after a biopsy of the right breast and uvula. To investigate the relationship of the delivery, lactation and MALT lymphoma, we examined the immunohistochemical analysis of hormone receptors. As a result, lymphoid cells of the breast were stained with anti-progesterone receptor antibodies in the cytoplasm. Consequently, the MALT lymphoma of the uvula appeared to be associated with SS. Moreover, hormones such as progesterone may have influenced the breast involvement of MALT lymphoma in our case.

Adult↗
PubMed2001

Zaltoprofen prevents carbon tetrachloride-induced reduction of body weight in rats.

Previously we reported carbon tetrachloride-induced body weight loss in rats as a new model of wasting disorders. The oral administration of a low dose of carbon tetrachloride to rats reduced the body weight and food intake at 24 h with a minimal effect on plasma alanine aminotransferase activity. Tumor necrosis factor-alpha, and cyclooxygenase-1 and -2 mRNA expression in the brain was not affected by carbon tetrachloride. Zaltoprofen, which is a non-steroidal anti-inflammatory drug, prevented the carbon tetrachloride-induced body weight decrease, without preventing the carbon tetrachloride-induced loss of food intake. The present results suggest the possible application of this drug for the treatment of wasting disorders.

Animals↗
PubMed2001

Development of anorexia in concanavalin A-induced hepatitis in mice.

Anorexia that develops in chronic hepatitis is associated with cytokine expression in the brain. Treatment of mice with concanavalin A (12.5 mg/kg, i.v.) elevated the plasma alanine aminotransferase activity at 8.5 h after treatment. Tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta mRNA expression was induced at 6 and 24 h after concanavalin A treatment in both the liver and brain. Treatment of mice with concanavalin A reduced the body weight at 24 h after treatment and this decreased body weight was accompanied by a decreased food intake. Glycyrrhizin (200 mg/kg, i.p.) inhibited the concanavalin A-induced elevation of plasma alanine aminotransferase activity, however, it did not inhibit the concanavalin A-induced decreased body weight. The present results indicate that treatment of mice with concanavalin A caused the development of anorexia and that this anorexia might develop independently of the induction of hepatitis.

Alanine Transaminase↗
PubMed2001

Inhibition of anti-Fas antibody-induced mice hepatitis by furocoumarin derivatives.

The effects of imperatorin and its synthetic derivative, Y355, on anti-Fas antibody-induced mice hepatitis were studied. Pretreatment of mice by intraperitoneal administration of imperatorine or Y355 at 30 mg/kg inhibited more than 80% of the anti-Fas antibody (150 microg/kg, i.v.)-induced elevation of plasma alanine aminotransferase activity. Furthermore, oral administration of imperatorin or Y355 at 100 mg/kg also had an inhibitory effect on anti-Fas antibody-induced hepatitis. Both compounds inhibited anti-Fas antibody (250 microg/kg)-induced caspase-1 and caspase-3 activities. The present results showed the inhibition of anti-Fas antibody-induced hepatitis by imperatorin and Y355, which might be a result of inhibition of caspase activities.

Alanine Transaminase↗
PubMed2001

[NMDA receptors and their interacting proteins in the postsynaptic density].

Glutamate receptors and their cytoplasmic interacting proteins are thought to play an important role in the process of excitatory synaptic transmission in the mammalian central nervous system. NMDA receptors are a subtype of ionotropic glutamate receptors and specifically interact with PDZ-domain containing proteins such as PSD-95. This interaction is important in the clustering of NMDA receptors on the postsynaptic membrane and the molecular complex containing NMDA receptors and PSD-95 is likely to be the core structure of the postsynaptic density. In the first part of this review, biological significance of the diversity of NMDA receptor subunits is discussed. In the second part, implications obtained from our recent analyses on the structural remodeling of the postsynaptic density are presented.

Animals↗
PubMed2001

Role of p38 mitogen-activated protein kinase in the healing of gastric ulcers in rats.

p38 belongs to the mitogen-activated protein kinase family and plays a crucial role in cellular responses to both cytokines and various stresses. We investigated the role of p38 in the healing of experimental gastric ulcers. Gastric ulcers were induced by submucosal injection of acetic acid solution into male rats. Western blotting and a kinase assay examined the p38 activity and phosphorylation state in ulcerated tisue. After orally administering FR167653 (p38 kinase inhibitor) for 3 to 14 days, the production level of cytokines and the protein-level expression of cyclooxygenase and inducible nitric oxide synthase were examined by enzyme-linked immunosorbent assay and Western blotting. Only in fibroblasts and macrophages/monocytes in ulcerated tissue, p38 was found to be phosphorylated with an elevated kinase activity level. FR 167653 inhibited the activity of p38, yet had no effect on its phosphorylation state. The drug significantly impaired ulcer healing (without affecting acid secretion) and angiogenesis in the ulcer base. The production of interleukin-1beta and tumor necrosis factor-alpha were significantly reduced after FR167653 treatment. In addition the expression of cyclooxygenase-2 and inducible nitric oxide synthase proteins increased PGE2 generation and NOx secretion in the ulcerated stomach were suppressed by FR167653. From these findings, we conclude that p38, activated by gastric ulceration, might play some role in the healing of gastic ulcers in rats.

Animals↗
PubMed2001

Involvement of heat shock proteins in the healing of acetic acid-induced gastric ulcers in rats.

The present study examined the expression of 73-kDa of heat shock cognate protein (HSC70), 72-kDa of heat shock protein (HSP70) and 47-kDa of HSP (HSP47) observed in the ulcer healing process in rats. Gastric ulcers were induced by a luminal application of acetic acid in male Donryu rats. During the ulcer healing process, the expression of HSPs in the ulcerated tissue was determined. A high level of HSC70 expression was observed both in the normal mucosa and ulcerated tissue, but the level did not change upon ulceration and ulcer healing. While HSP70 and HSP47 were markedly expressed in the ulcer base during ulceration, and decreased with ulcer healing. HSP70 expression in the ulcer margin was gradually increased with ulcer healing. Omeprazole accelerated the healing of gastric ulcers with strong inhibition of gastric acid secretion, while indomethactin delayed in ulcer healing despite slight inhibition of gastric acid secretion. Omperazole enhanced the expression of HSP70 both in the ulcer margin and base, but it reduced HSP47 expression in the ulcer base Indomethacin markedly enhanced HSP47 expression only in the ulcer base. In conclusion, the expression of HSP70 and HSP47 is changed during ulcer healing. Furthermore, it was suggested that the enhanced expression of HSP70 is involved in acceleration of ulcer healing, but overexpression of HSP47 is involved in delayed ulcer healing.

Animals↗
PubMed2001

Pharmacological regulation of gastric acid secretion in the apical membrane of parietal cells; a new target for antisecretory drugs.

We examined the local effect of several drugs against secretagogue-stimulated acid secretion in dogs. Test drugs were applied to denervated gastric pouches in conscious dogs either for 5 to 30 min beginning 1 hr after or for 30 min before intravenous infusion of gastric secretagogues (histamine, pentagastrin, or carbachol). The antisecretory effect of test drugs delivered by an intravenous or oral route was also examined. Local application of acid pump inhibitors (omeprazole, leminoprazole) for 30 min beginning 1 hr after histamine infusion significantly inhibited gastric acid secretion. The effect of leminoprazole persisted for more than 8 hr after a 30 min application. A mast cell stabilizer (FPL 52694) applied to pouches for 15 to 30 min also potently inhibited histamine-stimulated gastric acid secretion in a time-dependent manner. The duration of the antisecretory effect of such drugs after a 30 min application was greater than 4 hr. Locally applied leminoprazole and FPL 52694 for 30 min also significantly inhibited pentagastrin- and carbachol-stimulated gastric acid secretion. Although intravenous omeprazole and leminoprazole exerted a potent antisecretory effect on histamine-induced acid secretion FPL 52694 had little or no antisecretory effect following intravenous or oral administration. 16,16-dimethyl prostagladin E2 also locally inhibited histamine-stimulated acid secretion. Acid stable local anesthetics (tetracaine, ethyl-4-aminobenzoate), histamine H2-receptor blockers (cimetidine, ranitidine, and famotidine), and a muscarinic M1-receptor antagonist (pirenzepine) did not exhibit local antisecretory effects. Such results strongly suggest that the apical membrane of parietal cells possesses a pharmcologically sensitive portion similar to the basolateral membrane, which usually mediates gastric acid secretion. The apical membrane represents an intriguing target for new antisecretory drugs, as well as a new medium for further elucidating the functional features of parietal cells.

Animals↗
PubMed2001

CD56-Positive cutaneous lymphoma with multicentric Castleman's disease-like systemic manifestations.

We report a 55-year-old Japanese male with CD56+ cutaneous lymphoma. The patient had multiple cervical lymphadenopathy, a red nodule on his neck, and parotid gland nodularity. Histologic features of the biopsied cervical lymph node showed follicular hyperplasia with numerous plasma cells. A biopsied skin specimen of the nodule on his neck demonstrated dense infiltration of atypical large lymphocytes into the dermis. Immunohistochemical study of this specimen revealed CD3+, CD4+, and CD56+ expression in the majority of neoplastic cells. Polymerase chain reaction assays for the detection of Epstein-Barr virus sequences were positive for lymph node and skin DNA. Laboratory examinations showed polyclonal gammopathy, pancytopenia, and high serum interleukin-6 levels. These clinical and histological findings resembled those of multicentric Castleman's disease.

CD56 Antigen↗
PubMed2001

Clinicopathological study of mucous pooling referred to as mucinous component (MUC) in colorectal submucosal invasive carcinomas.

We investigated the significance of a pool of mucin, individually termed mucinous component (MUC), at the leading invasion edge of colorectal submucosal invasive carcinoma (SIC). In particular, we studied the correlation between pathological adverse prognostic factors and stainability of the mucosubstances and tumor-associated glycoconjugates in MUC. We demonstrated that MUCs were present in 21% of SICs, and 20% of SICs with MUC were involved in metastasis or recurrence, while only 6% of SICs without MUC were positive for it (p=0.005). SICs with MUC showed strong staining of carcinoembryonic antigen and Ulex europaeus I in the MUCs as well as in the cancer cells with high-grade atypia. Moreover, the mucins in MUCs predominantly stained for sialomucin. This study was the first to investigate the importance of mucous nodules in colorectal SIC. We concluded that MUC in SIC would be an important adverse prognostic factor, and that we should at least consider employing a similar treatment strategy for it to advanced colorectal carcinoma.

Adenocarcinoma↗
PubMed2001

Abdominosacral repair for a rectovaginal fistula with anastomotic stenosis after low anterior resection report of a case.

The management of a postoperative rectovaginal fistula after low anterior resection for rectal cancer is difficult and requires reconstruction of the anastomotic site and fistula. The results of reconstructive operation are often unsatisfactory. Herein, we describe our reconstruction technique using the posterior approach through the vaginal lumen for a high rectovaginal fistula repair. This reconstructive operation is useful for postoperative rectovaginal fistulas accompanied by severe stenosis of the anastomotic site following low anterior resection for rectal cancer.

Aged↗
PubMed2000

Inhibition of anti-Fas antibody-induced hepatitis by aminoguanidine in mice.

Aminoguanidine is an inhibitor of inducible nitric oxide synthase (iNOS) and is of potential clinical usefulness. Treatment of mice with anti-Fas antibodies (150 microg/kg, i.v.) induced elevation of plasma alanine aminotransferase activity at 4 h and this elevation was inhibited by pretreatment of mice with aminoguanidine (3, 10 and 30 mg/kg, i.p.). The anti-Fas antibody-induced elevation of caspase-3 activity was inhibited by aminoguanidine (30 mg/kg, i.p.), but the addition of aminoguanidine to the cytosol up to 10(-4) M did not inhibit the caspase-3 activity in vitro. Thus, aminoguanidine prevents anti-Fas antibody-induced hepatitis by affecting the apoptotic pathway upstream of caspase-3 activation.

Animals↗
PubMed2000

Impaired chemosensitivity and perception of dyspnoea in Parkinson's disease.

Exacerbation of respiratory failure in Parkinson's disease could be the result of impaired perception of hypoxia. We assessed chemosensitivity to hypoxia and hypercapnia and perception of dyspnoea on the Borg scale in 25 patients (Hoehn and Yahr stage 2-3) and 11 controls. Chemosensitivity to hypoxia, but not that in response to hypercapnia, was lower in patients than in controls (0.196 [SE 0.030] vs 0.525 [0.360]; p=0.012); the mean Borg score was lower in patients than in controls under hypoxic conditions (2.9 [SD 1.4] vs 4.8 [2.1]; p=0.0015). Thus, even at an early stage of disease, patients with Parkinson's disease had a subnormal hypoxic response accompanied by blunted perception of dyspnoea.

Awareness↗
PubMed2000

Mechanisms of cancer prevention by tea polyphenols based on inhibition of TNF-alpha expression.

Among various biochemical and biological activities of tea polyphenols, we believe inhibition of the expression and release of tumor necrosis factor-alpha (TNF-alpha) is crucial, since our study with TNF-alpha-deficient mice has revealed that TNF-alpha is an essential factor in tumor promotion. We found that EGCG dose-dependently inhibited AP-1 and NF-kappaB activation in BALB/3T3 cells treated with okadaic acid, resulting in inhibition of TNF-alpha gene expression. Furthermore, treatment with 0.1% green tea extract in drinking water reduced TNF-alpha gene expression as well as TNF-alpha protein level in the lung of TNF-alpha transgenic mice; and IL-1beta and IL-10 gene expression in the lung was also inhibited by treatment with green tea extract, indicating that green tea inhibits both TNF-alpha and the cytokines induced by TNF-alpha in organs. We recently found synergistic effects of EGCG and cancer preventive agents such as tamoxifen and sulindac, on cancer preventive activity. Taken together, the results show that green tea is efficacious as a non-toxic cancer preventive for humans.

3T3 Cells↗
PubMed2000

Refractory anemia with ringed sideroblasts with a low IPSS score progressed rapidly with de novo appearance of multiple karyotypic abnormalities and into acute erythroleukemia (AML-M6A).

We report here a case of refractory anemia with ringed sideroblasts (RARS) with a low risk group by the International Prognostic Scoring System (IPSS) at the time of diagnosis but had a rapid disease progression. Although the patient showed a normal male karyotype at the time of RARS diagnosis, his marrow cells had del(5)(q14) and add(17)(p12) abnormalities 2 months after the diagnosis, and later the marrow cells had multiple abnormalities and the patient expired 6 months after the initial diagnosis of RARS. The patient was diagnosed as having RARS with a low risk group by the IPSS classification, however, one should keep in mind that some patients with myelodysplastic syndromes with low risks by either the French-American-British (FAB) classification or the IPSS classification may have progressive disease and subsequential cytogenetic analysis could predict the disease progression.

Acute Disease↗