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Biomedical subjects

S Ogoshi

Publications and source records attributed to S Ogoshi.

At least 19 recordsLinked to original sources

Carbon-carbon bond formation by electrophilic addition at the central carbon of the mu-eta(3)-allenyl/propargyl ligand on the Pd-Pd bond.

The mu-eta(3)-allenyl/propargyldipalladium complexes were synthesized by the reaction of the corresponding eta(1)-allenyl- or eta(1)-propargylpalladium complexes with Pd(2)(dba)(3). The X-ray diffraction analysis indicates that the dinuclear complex has a unique structure, in which two palladium, three carbon, two phosphorus, and one halogen atoms are in the same plane. These dinuclear complexes react with electrophiles, such as HCl or AcCl, at the central carbon of the mu-eta(3)-allenyl/propargyl ligand to give the mu-eta(3)-vinylcarbenedipalladium complexes. Intramolecular reaction proceeded smoothly to give cyclization products quantitatively. Addition of a catalytic amount of a palladium(0) complex dramatically accelerated the carbon-carbon bond formation. The MO calculations on the mu-eta(3)-allenyl/propargyl complexes indicated that the reaction proceeds via orbital control.

Journal Article↗

Coordination of Lewis acid to eta(2)-enonepalladium(0) leading to continuous structure variation from eta(2)-olefin type to eta(3)-allyl type.

The reaction of alpha,beta-unsaturated carbonyl compounds, a palladium(0) complex, and Lewis acids led to the formation of a new class of complexes showing a wide variety of structures with eta(2)-type and eta(3)-type coordination of the carbonyl compounds. The reaction of Pd(PhCH=CHCOCH(3))(PPh(3))(2) with BF(3).OEt(2) or B(C(6)F(5))(3) quantitatively gave palladium complexes 1a,b having BX(3)-coordinated eta(2)-enonepalladium structure, as revealed by X-ray structure analysis of the B(C(6)F(5))(3) adduct 1b. On the other hand, the reaction of Pd(PhCH=CHCHO)(PPh(3))(2) with BF(3).OEt(2) or B(C(6)F(5))(3) gave distorted zwitterionic eta(3)-allylpalladium complexes 3a,b, where the Pd-carbonyl carbon distance in 3a (2.413(4) A) is much shorter than that (2.96(1) A) in 1b. The values of the P-P coupling constant and (13)C chemical shift for carbonyl carbon are useful criteria for predicting how the eta(3)-coordination mode contributes to the structure of the enone-palladium-Lewis acid system. Molecular orbital calculations on the series of model complexes suggest that orbital overlap in the highest occupied molecular orbital between the palladium and carbonyl carbon is enlarged by coordination of the Lewis acid to the carbonyl group. Palladium-catalyzed conjugate addition of R-M (R-M = AlMe(3), AlEt(3), ZnEt(2)) and its plausible reaction path are also reported.

Journal Article↗

Long-term graft acceptance in rat heart transplantation by CTLA4Ig gene transfection combined with FTY720 treatment.

CTLA4Ig strongly adheres to B7 molecules on antigen-presenting cells to block intracellular signal transduction via CD28 on helper T cells, which eventually inhibits immune responses. We have demonstrated that the administration to recipient animals of adenoviral vectors containing CTLA4Ig gene (adCTLA4Ig) prolonged graft survival, although the gene expression diminished in a time-dependent manner and the grafts were finally rejected. In addition, recipient animals treated with FTY720, a new immunosuppressant, exhibited a decrease in the number of peripheral lymphocytes due to apoptosis. In this study, we performed adCTLA4Ig transfection combined with FTY720 treatment in heart-grafted rats to determine if the combination could induce a mutual effect on graft survival. The recipient animals were given injections of 1 x 10(9) plaque-forming units of adCTLA4Ig via the tail vein immediately after grafting. On the day before transplantation we administered FTY720 orally to some of these animals at a dosage of 5 mg/kg and again on the day of transplantation. The median graft survival period in the adCTLA4Ig-only group was 27 days, whereas that in the combination group was markedly prolonged to 56 days. Of 15 grafts, 5 survived indefinitely. In these groups we observed detectable levels of CTLA4Ig in the sera 49 days after grafting; the levels were always higher in the combination group than in the adCTLA4Ig-only group. As a result, this study revealed that FTY720 and adCTLA4Ig have a potent mutual effect on graft survival during rat heart transplantation. Furthermore, it is highly possible that FTY720 enhances gene expression of adCTLA4Ig, which may be related to the long-term acceptance of grafts.

Abatacept↗

Route of feeding influences the production and expression of tumor necrosis factor alpha in burned rats.

The effect of nutritional route on tumor necrosis factor alpha (TNF-alpha) production in burned rats was examined. Scald burns covering about 30% of the whole body surface area were inflicted on 43 male Wistar rats weighing about 200g. The animals were divided into three groups: CHOW (n = 10), total parenteral nutrition (TPN) (n = 22), and total enteral nutrition (TEN) (n = 11), continuously given a chow diet, TPN solution, or an enteral diet, respectively, for 7 days after the burn injury. The rate of detection of TNF-alpha in plasma on day 7 was significantly higher in the TPN group than in the CHOW or TEN groups. The messenger RNA (mRNA) expression of TNF-alpha was significantly increased in the spleen, lungs, liver, and ileum of the rats receiving TPN compared with the CHOW and TEN rats. On the other hand, the expression of TNF-alpha mRNA was markedly decreased in the thymus of the TPN group compared with the CHOW group. The mortality rate in the TPN group (63.6%) was higher than that in the CHOW (0.0%) or TEN (27.3%) groups on day 7 after burn injury. These data suggest that TPN increases the expression of TNF-alpha mRNA in organ tissues and systemic TNF-alpha production, and reduces the survival rate of rats after thermal injury, but TEN does not.

Animal Feed↗

Expression of Bax and apoptosis-related proteins in human esophageal squamous cell carcinoma including dysplasia.

The rate of tumor growth depends on the balance between proliferation and death of tumor cells. It is known that Bax, caspase-3, and p53 proteins are death-promoting factors, whereas Bcl-2 protein is a death antagonist. We immunohistochemically examined the expression of Bax and apoptosis-related proteins such as caspase-3, p53, and Bcl-2 in 76 patients with human esophageal squamous cell carcinoma (SCC) including dysplasia to determine the relationship of expression of each protein to tumor behavior and patients' prognosis. No significant relationships in immunopositivity were found among these proteins in SCCs. Cytoplasmic Bax expression was exhibited in 63 cases of SCCs (82.9%). The apoptotic index of caspase-3-positive lesions was significantly higher than that of caspase-3-negative lesions in both dysplasia and SCC (P =.016, P =.012). On the other hand, the apoptotic index (1.18%) was significantly correlated with Bax overexpression in dysplasia (P =.006), but not in SCC lesions (P =.129). The patients with Bax-positive SCCs were found to have a poor prognosis by the Kaplan-Meier method (P =.043). These findings suggested that Bax expressed in dysplasia may play a role as an apoptotic factor, but that it may be functionally inactive in some cancerous lesions and thus not contribute to suppression of the tumor progression in some cases of human esophageal SCCs.

Apoptosis↗

Association between p53 immunostaining and cigarette smoking in squamous cell carcinoma of the esophagus.

BACKGROUND: It is generally accepted that cigarette smoking is closely associated with esophageal squamous cell carcinoma. This study investigated the molecular targets of cigarette smoke in carcinogenesis of the esophagus. METHODS: Seventy-four patients with esophageal squamous cell carcinoma (SCC) were grouped according to daily cigarette consumption: heavy smoking group (group H) (n = 26), moderate smoking group (group M) (n = 39) and non-smoking group (group N) (n = 9). We compared p53 and retinoblastoma (RB) expression among the three groups by immunohistochemistry. In addition, fresh tumor tissues from 30 smokers with esophageal SCC were tested for p53 mutations in exons 5-8 by direct sequencing. RESULTS: Staining for the p53 product was positive in 65.4% of group H, 38.5% of group M and 44.4% of group N. The frequency of positive staining in the group H was significantly higher than in group M (p = 0.033) and in group M + group N (p = 0.034). The difference with respect to the frequency of overexpression of RB was not significant. The patterns of p53 base-pair mutations in direct sequencing study were of five types, most commonly G:C to T:A transversion (35.3%). CONCLUSIONS: Our study suggests that one of the molecular targets of cigarette smoke is the p53 gene. The pattern of p53 point mutations involved a wide range of base-pair changes.

Aged↗

Effects of pimobendan and EGIS 9377, cardiotonic agents, and OG-VI, a nucleoside-nucleotide mixture, administered during reperfusion after ischemia on stunned myocardium in dogs.

BACKGROUND: Pimobendan is a so-called calcium sensitizer that exerts a positive inotropic action. EGIS 9377 is synthesized as a calcium sensitizer. OG-VI is a nucleoside-nucleotide mixture that ameliorates the myocardial dysfunction (myocardial stunning) after ischemia. OBJECTIVE: To determine whether administration of these agents after the onset of reperfusion after ischemia improves the condition of stunned myocardium. METHODS: Dogs anesthetized with pentobarbital were subjected to 20 min ligation of left anterior descending coronary artery and then 60 min reperfusion. The corresponding vehicle, 0.3 and 1 mg/kg pimobendan, or 1 and 3 mg/kg EGIS 9377 was injected intravenously 30 min after the onset of reperfusion. Saline solution or 1.2 mumol/kg per min OG-VI was infused for 30 min, starting 30 min after the reperfusion. Shortening of myocardial segment was measured by sonomicrometry. The tissue levels of energy and carbohydrate metabolites in the 60 min-reperfused hearts were determined. RESULTS: Shortening of myocardial segments significantly decreased during ischemia, and returned toward preischemic level after reperfusion for all groups, although the contractile dysfunction still remained. Injections and infusion of pimobendan, EGIS 9377, and OG-VI after the onset of reperfusion ameliorated the contractile dysfunction. Systemic vascular resistance was decreased by administrations of pimobendan and OG-VI. The levels of high-energy phosphates in 60 min-reperfused heart were not changed by either treatment. CONCLUSION: Administration of pimobendan, EGIS 9377, and OG-VI ameliorate the myocardial contractile dysfunction after ischemia even when these agents are administered after the onset of reperfusion. The increase in contractile function due to these agents did not worsen the myocardial energy balance.

Adenosine Triphosphate↗

Effect of administration of nucleosides and nucleotides on protein turnover and the hypoxic myocardium.

Nucleotides and nucleosides have effects on improving energy metabolism and enhancing immune function. Under a surgical stress, requirement of nucleotides are increased as well as nitrogen. A well-balanced nucleoside solution (OG-VI) was developed for parenteral administration and its effect was examined in animals. The OG-VI solution contained 3.11% of nucleosides which was composed of inosine, guanosine monophosphate, cytidine, uridine and thymidine of 4:4:4:3:1 in molar ratio. The whole body protein turnover increased significantly in rats received total parenteral nutrition (TPN) with OG-VI after 70% hepatectomy and enhanced the fractional protein synthesis rates of the muscle and liver. Also myocardial contractility (%segment shortening, %SS) in dogs after occlusion of left anterior descending artery (LAD) was recovered to 70% after reperfusion in the OG-VI group. The creatine phosphate (PCr) / inorganic phosphate (Pi) was maintained the baseline level and did not decrease after hypoxia in the OG-VI group while PCr/ Pi was decreased after hypoxia in normal rat. These data suggested that the nucleoside-nucleotide (OG-VI) improved nitrogen metabolism and might stimulate synthesis of high-energy phosphate in recovery after severe surgical stress.

Animals↗

Primary T-cell lymphoma of the duodenum: report of a case.

A case of primary non-Hodgkin's T-cell lymphoma of the duodenum is presented. A 41-year-old man was hospitalized in 1984 complaining of abdominal distention and vomiting. Hypotonic duodenography showed an encircling filling defect in the second portion of the duodenum, and a biopsy specimen revealed features of malignancy suggestive of either undifferentiated carcinoma or malignant lymphoma. Radical surgery (pancreaticoduodenectomy) was performed, after which chemotherapy was administered. A histological evaluation of the duodenal tumor showed it to be non-Hodgkin's lymphoma. It was a diffuse, large-cell type, which immunohistochemically suggested it to be of T-cell origin. Currently the patient is doing well, with no evidence of disease recurrence 13 years after surgery.

Adult↗

Determination of the prognostic significance of cyclin B1 overexpression in patients with esophageal squamous cell carcinoma.

Recent studies have identified a family of proteins referred to as cyclins, which control the cell cycle. Cyclin B1 activates cdc2, which regulates cell progression through the G2 and M phases. The main aim of this study was to examine the relationships between the cyclin B1 expression in human esophageal squamous cell carcinoma (SCC) and clinicopathological factors and prognosis of the patients. Eighty-seven cases of primary human SCC consecutively obtained at esophagectomy were immunohistochemically studied using an anti-human cyclin B1 protein antibody (2H1-H6). The relationship between cyclin B1 expression and clinicopathological factors, including prognosis, were also statistically assessed. Positive immunostaining of cancer cells, mainly in the cytoplasm, was detected in 72.4% (63/87): heterogeneous pattern in 37.9% (33/87) and homogeneous pattern in 34.5% (30/87). The prevalence of cyclin B1 expression was significantly higher in cases with invasion deeper than the muscularis propria (P<0.005) and with venous invasion (P<0.01) than in other cases. Patients whose SCCs expressed high levels of cyclin B1 protein had a significantly poorer prognosis than did the other patients (P<0.05). Multivariate analysis demonstrated that cyclin B1 status was an important factor affecting survival (P<0.05). These findings demonstrated that overexpression of cyclin B1 protein is associated with tumor behavior and prognosis for patients with human esophageal SCC.

Adult↗