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Biomedical subjects

T Okamura

Publications and source records attributed to T Okamura.

At least 91 records · Page 5Linked to original sources

[Effect of autologous platelet-rich plasma (PRP) in cardiac surgery].

Autologous platelet-rich plasma (PRP) was harvested before cardiopulmonary bypass (CPB). After heparin neutralization, it was returned to patients. The purpose of this study was to examine platelet function and the amount of blood loss and blood transfusion after transfusion of PRP. Twenty-eight patients undergoing elective coronary artery bypass grafting and other procedures were divided into three groups: group A; patients undergoing CAGB between May and October 1997 (n = 10), group B; patients undergoing other between May and October 1997 (n = 8), group C; patients undergoing CAGB before May 1997 (n = 10). Blood cell count, platelet aggregation in response to ADP, and platelet adhesion were measured before CPB, just after CPB, after infusion of protamine and PRP, 24 hrs after CPB and 48 hrs after CPB. Blood loss and blood transfusion in group. A and group C were examined after CPB. There was no significant difference in platelet count between group A and group B. There was significant difference in platelet aggregation in group A. There was no significant difference in blood loss after CPB between group A and group C, but there was a significant difference in blood transfusion between group A and group C. These results suggest that PRP was useful to preserve platelet function and to decrease blood loss after CPB in cardiac surgery.

Blood Transfusion, Autologous↗

[European-American-type hairy cell leukemia without splenomegaly, treated successfully with deoxycoformycin].

A 55-year-old Japanese man was hospitalized on October 5, 1999, because of high fever. Physical examination revealed neither lymphadenopathy nor hepato-splenomegaly. Laboratory data on admission showed a white blood cell count of 1,580/microliter, a hemoglobin level of 9.1 g/dl, and a platelet count of 113 x 10(3)/microliter. A small percentage of abnormal mononuclear cells were present in the peripheral blood. A bone marrow biopsy specimen demonstrated myelofibrosis and diffuse infiltration of abnormal monoculear cells with a mature B cell phenotype. A bone marrow aspirate showed 29% abnormal mononuclear cells, which had an indented or folded nucleus and reticular nuclear chromatin. Moderate to strong tartarate-resistant acid phosphatase activity was detected in these cells. Although the cytoplasmic projections were poorly preserved in specimens stained with May-Giemsa, fresh preparations showed numerous slender cytoplasmic projections by phase-contrast microscopy. The hairy cells had the phenotype CD5-, CD10-, CD11c+, CD19+, CD20+, CD25+, lambda. The patient was diagnosed as having European-American-type hairy cell leukemia (HCL) without splenomegaly, which is quite rare in Japan. The value of phase-contrast microscopy for recognition of the hairy cells was emphasized. The patient was treated successfully with deoxycoformycin (DCF).

Antibiotics, Antineoplastic↗

[Intramedullary spinal cord metastasis of lung adenocarcinoma causing Brown-Séquard Syndrome].

A 36-year-old woman admitted to our hospital because of numbness in the left limbs and weakness in the right arm, and was subsequently given a diagnosis of intramedullary spinal cord metastases from lung cancer. The patient had lung adenocarcinoma with metastases to the brain, spine and lymph nodes. Occipital craniotomy, radiation therapy and chemotherapy were performed on the lesions in the year following June 1994. In June 1995, however, she complained of numbness in the left limbs and weakness in the right arm. Compatible with her neurological manifestation, MRI demonstrated tumors in the right side of the cord at the spinal level of C3-4 and C7-Th1, both of which were of high density in T2-enhanced conditions with enhancement by gadolinium-diethylenetriamine pentaacetic acid. No invasion from spinal metastasis was detected by CT, scintigraphy or MRI. We therefore diagnosed her manifestation as Brown-Séquard syndrome caused by intramedullary spinal cord metastatic tumors of lung adenocarcinoma. In order to avoid paraplegia and dysfunction of the bladder and bowel, radiation therapy of the cord lesions with total dose of 44 Gy was performed. Her neurologic manifestation was improved, restoring her quality of life, as the tumor size estimated by MRI decreased. Four months later, however, she died of lung adenocarcinoma that developed accompanied with severe peritonitis carcinomatosa and multiple metastases.

Adenocarcinoma↗

Identification and characterization of two novel mutations (Q421 K and R123P) in congenital factor XII deficiency.

The factor XII genes of two unrelated factor XII-deficient Japanese families were screened, and two novel mutations were identified. A heterozygous mutation (Q421K) was identified in the gene of a cross-reacting material (CRM)-negative patient with reduced FXII activity (entitled Case 1). No mutations were discovered in the other allele. Case 2 was a CRM-negative patient with severe FXII deficiency. In this case, a homozygous mutation (R123P) was discerned. Expression studies in Chinese Hamster Ovary (CHO) cells demonstrated accumulation of mutant Q421 K factor XII in the cell, and insufficient secretion, while the R123P mutant showed lower levels of accumulation than wild-type, and no evidence of secretion in culture supernatant. In the presence of proteasome inhibitor, all types of FXII (wild-type. Q421K, R123P) accumulated in the cells. Protease protection experiments using the microsomal fraction of these cell lines demonstrated that while 20% wild-type FXII (total wild-type:100%) and 10% R123P mutant (total R123P-type: 40%) were resistant to treatment with trypsin, 50% Q421K-type FXII (total Q421K-type:130%) remained resistant to digestion. From these results, we conclude that Q421K is less susceptible to proteasome degradation than wild-type, but is unable to exit the ER efficiently, resulting in insufficient secretion phenotype. In contrast, R123P is susceptible to proteasome degradation and is not secreted.

Acetylcysteine↗

[CD34+ progenitor cell transplantation from HLA-mismatched donors to two patients with chronic active Epstein-Barr virus infection].

We report two boys with chronic active Epstein-Barr virus infection (CAEBV) refractory to conventional chemotherapy, who received HLA-mismatched allografts of CD34-positive progenitor cells from their fathers. One patient developed veno-occlusive disease (VOD) of the liver on day 18 after transplantation and died on day 26. The other patient received the allograft during partial remission. Although he suffered recurrent infections due to Streptococcus viridans, he is now doing well 23 months after transplantation. CAEBV refractory to chemotherapy is considered to be a fatal EBV-infected T/NK-cell lymphoproliferative disease, and our experiences suggest that CD34-positive progenitor cell transplantation for patients with CAEBV lacking HLA-matched donors may be a feasible and useful treatment. However, the timing of transplantation is considered to be critical, and should be performed when the patient is in good clinical condition.

Antigens, CD34↗

[Estimated relative and absolute risk for cardiovascular disease according to alcohol consumption increase in Japanese general population].

To calculate the estimated relative and absolute risks for cardiovascular diseases according to alcohol consumption increase, we performed a cross-sectional study of men aged 40-79 years using the data from the National Survey of Circulatory Disorders 1990 in Japan. First, we investigated the association between alcohol intake and two types of biochemical variables: serum lipids and blood pressure, by using analysis of variance. Then, concerning the subjects aged 40-59 years, linear regression analyses between alcohol intake and these biochemical markers were done to calculate regression coefficients adjusted for confounding factors. Finally, we substituted these regression coefficients for previously reported regression coefficients in Cox proportional hazard models to calculate relative and absolute risks for coronary heart disease and stroke. Alcohol intake positively correlated to systolic and diastolic blood pressure (SBP and DBP) and high-density lipoprotein cholesterol (HDLC). However, there was no relation between alcohol intake and serum total cholesterol. Linear regression coefficients of SBP, DBP and HDLC were 2.25, 1.43, 2.70, respectively. We used two proportional hazard regression formulas of Japanese population: one for coronary disease (Circulation 89, 2533-39) and the other for stroke (NIPPON DATA80, a 14-year cohort study of randomly selected Japanese). The estimated relative risks of coronary heart disease and stroke were 0.89 and 1.06 for 1 "go" (23 g of ethanol) increment of alcohol intake. The results indicate that the mortality rates shift from 0.44 to 0.39 per 1,000 person-years for coronary heart disease and from 0.76 to 0.81 per 1,000 person-years for stroke in the representative Japanese population aged 40-59 years. The absolute risk of cardiovascular disease may be unchanged if we assume 23 g increment of ethanol intake in Japan because the risk reduction in coronary heart disease was nearly equal to the risk increment in stroke.

Adult↗

Oral administration of tetrahydrobiopterin prevents endothelial dysfunction and vascular oxidative stress in the aortas of insulin-resistant rats.

We have reported that a deficiency of tetrahydrobiopterin (BH(4)), an active cofactor of endothelial NO synthase (eNOS), contributes to the endothelial dysfunction through reduced eNOS activity and increased superoxide anion (O(2)(-)) generation in the insulin-resistant state. To further confirm this hypothesis, we investigated the effects of dietary treatment with BH(4) on endothelium-dependent arterial relaxation and vascular oxidative stress in the aortas of insulin-resistant rats. Oral supplementation of BH(4) (10 mg. kg(-1). d(-1)) for 8 weeks significantly increased the BH(4) content in cardiovascular tissues of rats fed high levels of fructose (fructose-fed rats). Impairment of endothelium-dependent arterial relaxation in the aortic strips of the fructose-fed rats was reversed with BH(4) treatment. The BH(4) treatment was associated with a 2-fold increase in eNOS activity as well as a 70% reduction in endothelial O(2)(-) production compared with those in fructose-fed rats. The BH(4) treatment also partially improved the insulin sensitivity and blood pressure, as well as the serum triglyceride concentration, in the fructose-fed rats. Moreover, BH(4) treatment of the fructose-fed rats markedly reduced the lipid peroxide content of both aortic and cardiac tissues and inhibited the activation of 2 redox-sensitive transcription factors, nuclear factor-kappaB and activating protein-1, which were increased in fructose-fed rats. The BH(4) treatment of control rats did not have any significant effects on these parameters. These results indicate that BH(4) augmentation is essential for the restoration of eNOS function and the reduction of vascular oxidative stress in insulin-resistant rats.

Administration, Oral↗

Plasma fibrinogen and coronary heart disease in urban Japanese.

There is little information on the relation of plasma fibrinogen concentration to the risk of coronary heart disease in Asians, including Japanese, whose plasma fibrinogen concentration has been reported to be low by Western standards. The authors conducted a prospective study with 4.8 years of follow-up of 11,977 men and women aged 21-89 years (mean value of fibrinogen = 267 mg/dl) living or working in Osaka, Japan, in 1990-1996 to examine the relation of plasma fibrinogen with the incidence of coronary heart disease (myocardial infarction and angina pectoris). Mean fibrinogen concentration was 293.6 mg/dl for men who developed coronary heart disease (n = 35) compared with 261.6 mg/dl for men free of coronary heart disease (n = 8,094; difference, p < 0.01), and 355.2 mg/dl for women who developed coronary heart disease (n = 6) compared with 276.8 mg/dl for women free of coronary heart disease (n = 3,842; difference, p < 0.01). With a Cox proportional hazards model to adjust for cardiovascular risk factors, the relative risk for the highest fibrinogen quartile (> or =295 mg/dl) compared with the lowest (<228 mg/dl) was 4.8 (95% confidence interval: 1.4, 16.8, p = 0.01) for coronary heart disease, and 3.8 (95% confidence interval: 1.1, 13.4, p = 0.04) for myocardial infarction. Plasma fibrinogen is useful to predict the risk of coronary heart disease among urban Japanese, whose mean plasma fibrinogen is relatively low.

Adult↗

Antinociceptive effect of cilnidipine, a novel N-type calcium channel antagonist.

We investigated the antinociceptic effects of cilnidipine, a dihydropyridine derivative which acts on both L- and N-type voltage-dependent calcium channels, in mice. Intrathecally injected cilnidipine showed significant analgesic effect in formalin test. Cilnidipine significantly suppressed N-type currents in dorsal root ganglion (DRG) cells. Our findings apparently support the idea that cilnidipine attenuates synaptic neurotransmission by inhibiting N-type calcium channels in DRG neurons.

Animals↗

Evaluation of endothelial free radical release by vascular tension responses in insulin-resistant rat aorta.

Mechanical responses to superoxide anion scavengers and nitric oxide (NO) synthase inhibitors in aortic endothelial cells were compared in normal chow-fed rats and those made insulin-resistant by feeding of fructose. Cu(2+), Zn(2+)-superoxide dismutase-induced vascular relaxation and superoxide production, measured by the lucigenin-enhanced chemiluminescence method, were greater in aortas from fructose-fed rats than in those from normal chow-fed rats. N(G)-nitro-L-arginine-induced contractions due to suppression of NO synthase activity were smaller in aortas from fructose-fed rats. Vascular mechanical responses may reflect the generation of superoxide and NO by the endothelium. Thus, isometric tension studies may be a useful tool for evaluating the production of these radicals in blood vessels.

Animals↗

Serial analysis of MLL-AF4 chimeric message through successful bone marrow transplantation in a patient with t(4;11)-positive infant-ALL.

A 28-month-old girl with acute lymphoblastic leukemia (ALL) showing a t(4;11)(q21;q23) karyotype successfully underwent allogeneic bone marrow transplantation (BMT) at relapse. The chimeric MLL-AF4 message on her bone marrow (BM) specimens, examined by reverse transcriptase-polymerase chain reaction, was detectable at diagnosis, relapse, and just before BMT but became undetectable following BMT. She has since maintained complete remission. This observation suggests that detection of the chimeric message in BM may be useful to predict clinical outcome in patients with t(4;11) ALL.

Biomarkers, Tumor↗

Expression of the SART1 tumor-rejection antigens in colorectal cancers.

PURPOSE: Colorectal cancer is one of the major causes of cancer death in the world, including in the United States and Japan. We recently identified the tumor-rejection antigen gene SART1, which encodes both the SART1(259) antigen expressed in the cytosol of epithelial cancers and the SART1(800) antigen expressed in the nucleus of the majority of proliferating cells. This study investigated the expression of these tumor antigens to explore a potential molecule for specific immunotherapy of colorectal cancer patients. METHODS: SART1 antigens were investigated by Western blotting in six colorectal cancer cell lines and in 33 colorectal cancer tissues. The cancer cell lines were tested for their ability to stimulate interferon-gamma production by the human-leukocyte-antigen-A24-restricted and SART1-specific cytotoxic T lymphocytes and were also tested for their susceptibility to the lysis by the cytotoxic T lymphocytes. RESULTS: The SART1(259) antigen was detected in the cytosol of four of six cancer cell lines, 13 of 33 (39 percent) cancer tissues, and 0 of 20 nontumorous colorectal tissues. The SART1(800) antigen was expressed in the nucleus of all the colorectal cancer cell lines, 18 of 33 (55 percent) cancer tissues, and 0 of 20 nontumorous tissues. The human-lymphocyte-antigen-A24-restricted and SART1-specific cytotoxic T lymphocytes killed the human-lymphocyte-antigen-A24+ SART1(259+) cancer cells. CONCLUSIONS: The SART1(259) antigen could be an appropriate target molecule for specific immunotherapy of approximately 40 percent of the human-lymphocyte-antigen-A24+ patients with colorectal cancer.

Adenocarcinoma↗

Mechanisms underlying endothelium-dependent, nitric oxide/prostacyclin-independent, acetylcholine-induced relaxation in canine corpus cavernosum.

The mechanisms underlying endothelium-dependent and nitric oxide (NO)/prostacyclin-independent, acetylcholine-induced relaxation in isolated canine corpus cavernosum were investigated. In isolated canine corpus cavernous strips treated with indomethacin (10(-6) M) and N(G)-nitro-L-arginine (10(-4) M), acetylcholine produced relaxations in a concentration-dependent manner. The relaxations were not affected by treatment with 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazole-1-oxyl 3-oxide, sodium salt (carboxy PTIO, 3 x 10(-4) M), glibenclamide (10(-6) M), iberiotoxin (10(-7) M) or charybdotoxin (10(-7) M), but were abolished or reversed to contractions by treatment with apamin (10(-8) M) or scyllatoxin (10(-8) M). Levcromakalim (10(-7)-10(-6) M) induced a concentration-dependent relaxation which was abolished by treatment with glibenclamide (10(-6) M), but was not affected by treatment with apamin (10(-8) M) or scyllatoxin (10(-8) M). These findings indicate that endothelial cells of canine corpus cavernosum have an ability to produce a relaxing substance(s) other than NO or prostacyclin in response to acetylcholine. The substance(s) may open solely small conductance Ca2+-dependent K+ channels.

Acetylcholine↗