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Biomedical subjects

T Hamazaki

Publications and source records attributed to T Hamazaki.

At least 37 records · Page 2Linked to original sources
PubMed2000

[Prophylaxis with FK-506 for graft-versus-host disease after transplantation of bone marrow from unrelated donors].

Forty-eight patients who underwent bone marrow transplantation (BMT) from serologically HLA-matched unrelated donors received tacrolimus (FK506) alone or with methotrexate (MTX) and/or methylprednisolone (mPSL) to prevent graft-versus-host disease (GVHD). We analyzed retrospectively the efficacy of FK506 for GVHD prophylaxis, and its toxicity, by comparing three groups of patients: those given FK506 alone, those given FK506 + mPSL, and those given FK506 + MTX + mPSL. Grade III and IV acute GVHD occurred in five of 10 patients given FK506 alone and in 11 of 30 patients given FK506 + mPSL. In these groups, severe acute GVHD was commonly seen in the patients who discontinued FK506 administration early after BMT and in those who received bone marrow from genotypically HLA-mismatched donors. Early withdrawal of FK506 was due mainly to severe nephrotoxicity. The incidence of nephrotoxicity was very high in patients who received high-dose FK506 as well as melphalan-containing preconditioning (80% and 50%). None of eight patients who received FK506 + mPSL + MTX developed grade III-IV acute GVHD even though five of them received bone marrow from genotypically HLA-mismatched donors. In patients receiving bone marrow from unrelated donors, adjustment of the initial dose of FK506 seems essential in order to avoid severe nephrotoxicity, and combination of MTX and FK506 is useful for preventing severe acute GVHD.

Adolescent↗
PubMed1999

Administration of docosahexaenoic acid influences behavior and plasma catecholamine levels at times of psychological stress.

The purpose of the present research was to clarify the effect of docosahexaenoic acid (DHA) intake on behavior and plasma catecholamines (CA). In Study 1, 42 students took either DHA-rich oil capsules containing 1.5-1.8 g DHA/d or control oil capsules containing 97% soybean oil plus 3% of another fish oil for 3 mon in a double-blind fashion. They took a psychological test (PF Study) at the start and end of the study. This study started at the end of summer vacation and ended just before the final exams. In the control group, external aggression (aggression against others) in PF Study was significantly increased at the end of the study as compared with that measured at the start (+8.9%), whereas it was not significantly changed in the DHA group (-1.0%). In a similar double-blind study (Study 2), we measured external aggression under nonstressful conditions. External aggression slightly decreased in the control group, whereas there were no significant changes in the DHA group. In Study 3 with 14 students, plasma CA were measured at the start and end of capsule administration period of 2 mon. Subjects were under continuous stress of the final exams that lasted throughout the whole study period. The ratio of plasma epinephrine to norepinephrine concentrations was significantly increased in the DHA group (78%), whereas it stayed at the same level in the control group. In Study 4, mice were fed either DHA-deficient diet or -sufficient diet for 4 wk, and their rearing frequency (an anxiety index) was measured. In the DHA-sufficient group, the rearing frequency was significantly less than in the other group. These effects of DHA intake may be applied to people in an attempt to ameliorate stress-related diseases.

Adult↗
PubMed1999

Joint effects of HMG-CoA reductase inhibitors and eicosapentaenoic acids on serum lipid profile and plasma fatty acid concentrations in patients with hyperlipidemia.

HMG-CoA reductase inhibitors reduce serum total cholesterol concentrations and the risk of coronary heart disease in patients with hypercholesterolemia. Recently, it has been reported that patients with combined hyperlipidemia are also at risk of coronary heart disease. However, HMG-CoA reductase inhibitor therapy alone does not sufficiently reduce serum triglyceride concentrations. Epidemiological and clinical evidence has shown that fish oil can lower plasma lipid levels, especially triglycerides. Consequently, we investigated the effects of the combination of HMG-CoA reductase inhibitors and eicosapentaenoic acid, a major component of fish oil, on hyperlipidemia. We administered 900-1,800 mg/day of the ethyl ester of eicosapentaenoic acid to patients with hyperlipidemia who had been treated with HMG-CoA reductase inhibitors for 30 +/- 6 months (means +/- SE). Serum total cholesterol and triglyceride concentrations were significantly decreased 3 months after the administration of eicosapentaenoic acid (from 5.63 +/- 0.23 mmol/l to 5.02 +/- 0.20 mmol/l, P < 0.05; from 2.07 +/- 0.41 mmol/l to 1.08 +/- 0.17 mmol/l, P < 0.01, respectively). Serum high-density lipoprotein-cholesterol concentrations were significantly increased after the treatment (from 1.23 +/- 0.12 mmol/l to 1.34 +/- 0.13 mmol/l, P < 0.05). Plasma eicosapentaenoic acid concentrations and the ratio to arachidonic acid in plasma were also significantly increased 3 months after the treatment (from 101.9 +/- 8.1 mg/l to 181.8 +/- 23.9 mg/l, P < 0.001; from 0.640 +/- 0.075 to 1.211 +/- 0.170, P < 0.001, respectively). These results suggested that the combination therapy of HMG-CoA reductase inhibitors and eicosapentaenoic acid was effective for patients with hyperlipidemia.

Aged↗
PubMed1999

Monokine stimulation of interleukin-11 production by human vascular smooth muscle cells in vitro.

Human vascular smooth muscle cells (VSMC) are a component of blood vessels, and secrete a variety of cytokines in atherosclerotic loci. Interleukin-11 (IL-11), a member of IL-6-like cytokines, is reported to be involved in inflammation and tissue remodeling, both of which are observed in atherosclerosis. However, no information is available as to the production of IL-11 by VSMC. Therefore, the expression of IL-11 in VSMC is investigated. The amounts of IL-11 protein and mRNA were determined by enzyme-linked immunosorbent assay (ELISA) and Northern blot analysis, respectively. The expression of IL-11 in VSMC was also immunohistochemically determined. IL-1 alpha, transforming growth factor-beta (TGF beta) and, to a lesser extent, tumor necrosis factor-alpha (TNF alpha) stimulated the IL-11 production by VSMC, and the stimulatory effects of IL-1 alpha and TGF beta on IL-11 production were dose-dependent. IL-1 alpha and TNF alpha synergistically augmented TGF beta-stimulated IL-11 production by VSMC. Immunohistochemical staining also revealed the expression of IL-11 protein in VSMC. Furthermore, IL-1 alpha, TGF beta, and TNF alpha induced IL-11 gene expression in VSMC. Because IL-6-like cytokines are reported to be cytoprotective, monokine-stimulated IL-11 may have a potent protective role in atherosclerotic lesions.

Arteriosclerosis↗
PubMed1999

Effects of microgravity on c-fos gene expression in osteoblast-like MC3T3-E1 cells.

The paper summarizes the data on proliferation and gravity-related gene expression of osteoblasts that were obtained from an experiment conducted under simulated and real microgravity conditions. Simulated microgravity conditions obtained in a clinostat depress proliferation of both osteoblast-like MC3T3-E1 and HeLa carcinoma cells. This depression of proliferation occurs in a collagen gel culture in which the flow of culture medium by rotation may be reduced. Interestingly, MC3T3-E1 cells which are probably one of target cells to microgravity are more sensitive than the HeLa cells. Simulated microgravity inhibited the epidermal growth factor (EGF)-induced c-fos gene expression in the MC3T3-El cells. To examine in detail the effect of real microgravity on the EGF signal transduction cascade in osteoblasts, MC3T3-E1 cells were cultured in the Cell Culture Experiment Module of the sounding rocket TR-1A6. The EGF-induced c-fos expression in cells was depressed under short-term microgravity conditions in the sounding rocket, while the phosphorylation of mitogen-activated protein kinase (MAPK) was not affected compared with the controls grown on the ground. These results suggest that an action site of microgravity in the signal transduction pathway may be downstream of MAPK.

Animals↗
PubMed1999

The effect of docosahexaenoic acid on plasma catecholamine concentrations and glucose tolerance during long-lasting psychological stress: a double-blind placebo-controlled study.

We previously found that docosahexaenoic acid (DHA) intake prevented aggression from increasing at times of mental stress. In the present study, we investigated whether DHA intake modified the plasma catecholamines and cortisol of medical students during a 9-wk period of final exams. We also investigated the effects of DHA intake on a 75 g oral glucose tolerance test (oGTT). Fourteen medical students participated in the present study. They were randomly allocated to either control or DHA group in a double-blind manner. Subjects in the control group (4 males and 3 females) took 10 control capsules/d, each capsule containing 280 mg of mixed plant oil, and those in the DHA group (4 males and 3 females) took 10 DHA capsules/d containing 1.5 g DHA for 9 wk, during which subjects underwent more than 20 stressful final exams. At the start and end of the study, plasma catecholamines (epinephrine, norepinephrine (NE) and dopamine) and cortisol were measured; a 75 g oGTT was also performed. There were no intra- or intergroup differences in plasma glucose concentrations. However, NE concentrations were significantly reduced after DHA administration (-31%, p < 0.03). The other catecholamines and cortisol did not change significantly. The plasma ratio of epinephrine to NE increased in every DHA subject (+78%, p < 0.02), and intergroup differences were significant (p < 0.03). We conclude that these effects of DHA may be applied to people under long-lasting psychological stress to prevent stress-related diseases.

Adult↗
PubMed1998

Effect of HMG-CoA reductase inhibitors on plasma polyunsaturated fatty acid concentrations in patients with hyperlipidemia.

We investigated the effect of 12 months' HMG-CoA reductase inhibitor treatment on plasma polyunsaturated fatty acid concentrations in 19 patients with hyperlipidemia. Arachidonic acid concentrations were significantly increased following treatment (from 110.1 +/- 20.4 mg/l to 129.2 +/- 31.6 mg/l, P < 0.05). The ratio of eicosapentaenoic acid to arachidonic acid was significantly decreased at the end of 12 months' treatment (from 0.702 +/- 0.370 to 0.541 +/- 0.204, P < 0.05). These results suggest that HMG-CoA reductase inhibitors may increase the synthesis of metabolites from arachidonic acid in patients with hyperlipidemia, and that the addition of fish oil is more effective for the prevention of coronary heart disease than HMG-CoA reductase inhibitors alone.

Aged↗
PubMed1998

Docosahexaenoic acid does not affect aggression of normal volunteers under nonstressful conditions. A randomized, placebo-controlled, double-blind study.

We previously found that docosahexaenoic acid (DHA) intake prevents aggression enhancement at times of mental stress. In the present study we investigated changes in aggression under nonstressful conditions. Forty-six students of two universities took either DHA-rich fish oil capsules containing 1.5 g DHA (DHA group: 13 males and 9 females) or control oil capsules containing 97% soybean oil plus 3% of another fish oil (control group: 11 males and 13 females) for 3 mon in a double-blind fashion. At the start and end of the study they took an aggression-estimating test (P-F Study) without a stressor component. DHA (5.9 to 8.5%, P < 0.001) and eicosapentaenoic acid (0.7 to 1.5%, P < 0.001) increased in red blood cell phospholipids in the DHA group, while linoleic acid increased slightly (8.3 to 9.1%, P < 0.002) in the soybean oil control group. In the control group, measured aggression levels decreased from 34.8 to 29.4% (P < 0.005), whereas they remained stable in the DHA group (33.5 to 33.8%). The intergroup differences (-5.4 vs. 0.3%) were marginally significant (P < or = 0.05). Aggression levels were stable in the DHA group whether there was stressor (as previously shown) or not. This effect of DHA appears to be interesting, considering the reported association between a low intake of n-3 fatty acids and depression.

Adult↗
PubMed1998

Clinorotation reduces number, but not size, of cartilaginous nodules formed in micromass cultures of mouse limbbud cells.

In previous studies we used a ground based model to investigate the cellular responses to microgravity by exposing micromass cultures of embryonic limb cells to simulated weightlessness on a clinostat. Cultures set up in T-flasks and rotated at 30 rpm showed that clinostatted cultures had less chondrocyte differentiation than stationary or rotation controls, as assessed by number of nodules/culture stained with cartilage specific Alcian blue. In the current study, nodule size and shape of these nodules was assessed by interactive measurement of area, perimeter, circularity, and equivalent diameters, using the Optimas imaging software. Results show no significant difference in any of the measurements, indicating that clinorotation has no effect on expansion of the nodules either by differentiation of cells within the nodule, or by recruitment of cells into the nodule. The reduction in number of nodules without an alteration in size and shape indicates that the effect of simulated microgravity is to reduce the cell interactions required for the initial condensation of cells into a nodule, probably by interference with cell adhesion molecules.

Animals↗
PubMed1998

Diuretic response to cyclophosphamide in rats bearing a matrix metalloproteinase-9-producing tumour.

When cyclophosphamide (CY) (100-120 mg kg(-1)) was administered intravenously (i.v.) to normal F-344 rats, oliguria occurred over the 5-day observation period. Conversely, in rats bearing matrix metalloproteinase-9 (MMP-9) producing 13762NF mammary adenocarcinoma (MTLn3 clone), polyuria occurred chiefly during the first 24 h after CY treatment. In parallel with urine volume, a decrease in the urinary excretion of N-acetyl-beta-D-glucosaminidase (NAG) was observed during the first 5 days after CY treatment in normal rats, but it increased in MTLn3-bearing rats. No elevation in blood urea nitrogen (BUN) or serum creatinine (Cr) values was observed for either group. Both urine volume and urinary excretion of NAG after CY treatment were lower in rats bearing the MTC clone (lower production of MMP-9) than for those bearing the MTLn3 clone. In the case of treatment with cisplatin (CDDP, 4-6 mg kg(-1)), urine volume, urinary NAG excretion and BUN and serum Cr values all increased in normal rats and were all found to be higher in MTLn3-bearing rats than in normal rats. The diuretic response to these drugs in tumour-bearing (TB) rats may be associated with MMP-9 produced by the tumour cells. This report suggests that the nephrotoxicity due to anti-cancer drugs may change when the drugs are used for the treatment of patients bearing a MMP-9-producing tumour.

Adenocarcinoma↗
PubMed1997

The effects of infusion of trieicosapentaenoyl-glycerol emulsion on extravascular lung water during myocardial ischemia and reperfusion in dogs.

To test the effects of eicosapentaenoic acid (EPA) infusion on pulmonary edema induced by coronary ligation and reperfusion, extravascular lung water (EVLW) was measured in situ by the thermal-dye double indicator dilution method in dogs. In the control group of five dogs, 30 mL of a 10% soybean oil emulsion was infused through a leg vein. One hour after infusion, the left anterior descending coronary artery below the first diagonal branch was ligated for 15 min and then reperfused for 30 min. In the EPA group, six dogs were similarly treated with an emulsion of a 10% trieicosapentaenoyl-glycerol (90% pure). EVLW, pulmonary capillary wedge pressure, mean pulmonary artery pressure, mean blood pressure, and cardiac index were measured before and 15 min after coronary ligation, and 15 min and 30 min after coronary reperfusion. There were no significant differences in the hemodynamic indices between the two groups. EVLW significantly increased up to two times of baseline during coronary ligation in the control group (P < 0.05) and more during reperfusion (P < 0.01), whereas EVLW did not increase in the EPA group. In conclusion, EPA inhibited EVLW accumulation and may be useful for ameliorating one of the ischemia-reperfusion-induced complications, pulmonary edema.

Animals↗
PubMed1996

Characterization of DNA-binding proteins and protein kinase activities in Chlorella virus CVK2.

Several capsid proteins were selectively released from the viral core of Chlorella virus CVK2 by treatment with 4M urea. Among the viral core proteins, seven species (Vp154, Vp73, Vp63, Vp52, Vp48, Vp42, and Vp25) were shown to have DNA-binding activities by Southwestern blot analysis. Except for Vp154 and Vp25, these DNA-binding proteins showed a specific affinity for the viral genomic DNA. The viral core also contained three proteins with protein kinase activity (Vp73, Vp60, and Vp37); Vp73 seemed to have both DNA-binding and protein kinase activities. Antisera raised against Vp73 were used to screen a lambda-CVK2 expression library for the gene encoding Vp73. Three different clones (Vp73-3, Vp73-29, and Vp73-42) were obtained and analyzed. ORFs found in these clones all contained characteristic proline-rich motifs. The Vp73-42 ORF showed a strong similarity with histone H1 of various organisms and the Vp73-29 ORF contained two regions with leucine-zipper motifs. All three genes were expressed late in infection.

Amino Acid Sequence↗
PubMed1996

The effect of docosahexaenoic acid on aggression in young adults. A placebo-controlled double-blind study.

41 students took either docosahexaenoic acid (DHA)-rich oil capsules containing 1.5-1.8 grams DHA/day (17 females and 5 males) or control oil capsules containing 97% soybean oil plus 3% fish oil (12 females and 7 males) for 3 mo in a double-blind fashion. They took a psychological test (P-F Study) and Stroop and dementia-detecting tests at the start and end of the study. The present study started at the end of summer vacation and ended in the middle of mental stress such as final exams. In the control group extraggression (aggression against others) in P-F Study was significantly increased at the end of the study as compared with that measured at the start (delta = +8.9%, P = 0.0022), whereas it was not significantly changed in the DHA group (delta = -1.0%). The 95% CI of differences between the DHA and control groups were -16.8 to -3.0%. DHA supplementation did not affect the Stroop and dementia-detecting tests. Thus, DHA intake prevented extraggression from increasing at times of mental stress. This finding might help understand how fish oils prevent disease like coronary heart disease.

Adult↗
PubMed1996

Platelet and aorta arachidonic and eicosapentaenoic acid levels and in vitro eicosanoid production in rats fed high-fat diets.

There is a significant interest in the interrelationship between long-chain n-3 and n-6 fatty acids due to their ability to modulate eicosanoid production. In general, the intake of arachidonic acid (AA) results in enhanced eicosanoid production, whereas n-3 polyunsaturated fatty acids (PUFA) decrease the production of eicosanoids from AA. The purpose of this study was to investigate whether the effects of dietary AA on eicosanoid production in the rat were correlated with the AA and EPA levels in platelets and aorta (eicosanoid-producing tissues). Four groups of male Sprague-Dawley rats were fed a high-fat diet enriched with eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) (approximately 100 mg/day of EPA + DHA) for 24 d. During the last 10 d, the four groups were orally supplemented with 0, 30, 60, and 90 mg/day of ethyl arachidonate. A further group of rats was fed a control diet (without long-chain n-3 PUFA) for 24 d. In vitro aorta prostacyclin (PGI2) production, serum thromboxane A2 (TxA2) production and plasma, and platelet and aorta phospholipid (PL) fatty acids were measured. Enriching the diet with n-3 PUFA resulted in significant reductions in tissue AA levels and an increase in the n-3 PUFA, particularly EPA. On this diet, the AA to EPA ratio was 1:1 in platelet PL, and it was 2:1 in the aorta PL. There were significant decreases in the in vitro PGI2 and TxA2 production compared with the control animals. The inclusion of AA in the diet resulted in marked increases in AA levels in the platelet and aorta PL with corresponding decreases in EPA. The lowest dose of AA (30 mg/rat) reversed the effects of 100 mg/day of n-3 PUFA on AA levels in platelet and aortic PL and on in vitro aorta PGI2 and serum TxA2 production. The dietary AA caused a differential (twofold) increase in TxA2 relative to PGI2 for all three levels of AA supplementation. There were greater changes in the levels of AA and/or EPA in platelet PL compared with the aorta PL, which might have accounted for the differential effects of these PUFA on thromboxane production compared with PGI2 production in this study.

Animal Feed↗
PubMed1996

Effect of dietary n-9 eicosatrienoic acid on the fatty acid composition of plasma lipid fractions and tissue phospholipids.

n-9 Eicosatrienoic acid (ETrA), also known as Mead acid, is a minor fatty acid in essential fatty acid (EFA)-sufficient healthy subjects but is found at increased levels in EFA deficiency. This study examined the influence of dietary ETrA from a biological source on plasma and tissue ETrA. A synthetic fat-free diet was prepared to which was added Mut 48 oil which contains 19% ETrA (wt%) as well as other n-9 fatty acids. Blends of vegetable oils were used to achieve overall diets with 5% fat (wt%) and varying amounts of ETrA at two different dietary levels of linoleic acid (LA), approximately 4.4 and 19% of total fatty acids. These diets were fed to 5-week-old Dark Agouti rats for four weeks. Plasma lipid fractions and liver, spleen, and peritoneal exudate (PE) cells were analyzed for fatty acid composition. ETrA was present at up to 20% total fatty acids in plasma triglyceride, cholesterol ester, and phospholipid fractions. ETrA also accumulated to substantial levels in phospholipids of liver and spleen (up to 15% of total fatty acids) and PE cells (up to 11%). ETrA was found in plasma and tissue phospholipids in proportion to the amount of ETrA present in the diet. The incorporation was reduced in diets with higher LA content compared to diets containing similar amounts of ETrA but lower LA. All rats remained apparently healthy, and histological survey of major organs revealed no abnormality. While the long-term implications for health of ingestion of diets rich in ETrA remain to be established, rats appear to tolerate high levels of dietary ETrA without adverse effects. Dietary enrichment with ETrA warrants further investigation for possible beneficial effects in models of inflammation and autoimmunity, as well as in other conditions in which mediators derived from n-6 fatty acids can affect homeostasis adversely.

8,11,14-Eicosatrienoic Acid↗