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N Hata

Publications and source records attributed to N Hata.

At least 19 recordsLinked to original sources

Dietary docosahexaenoic acid ameliorates, but rapeseed oil and safflower oil accelerate renal injury in stroke-prone spontaneously hypertensive rats as compared with soybean oil, which is associated with expression for renal transforming growth factor-beta, fibronectin and renin.

We have noted that n-3 fatty acid-rich oils, such as fish oil, perilla oil and flaxseed oil as well as ethyl docosahexaenoate (DHA) prolonged the survival time of stroke-prone spontaneously hypertensive rats (SHRSP) rats by approximately 10% as compared with linoleate (n-6)-rich safflower oil. Rapeseed oil with a relatively low n-6/n-3 ratio unusually shortened the survival time by approximately 40%, suggesting the presence of minor components unfavorable to SHRSP rats. This study examined the effects of dietary oils and DHA on renal injury and gene expression related to renal injury in SHRSP rats. Rats fed rapeseed oil- and safflower oil-supplemented diets developed more severe proteinuria than those fed soybean oil-supplemented diet used as a control, but there were no significant differences in blood pressure. In contrast, the DHA-supplemented diet inhibited the development of proteinuria and suppressed hypertension. The mRNA levels for renal TGF-beta, fibronectin and renin were higher in the rapeseed oil and safflower oil groups after 9 weeks of feeding of the experimental diet than in the soybean oil and DHA groups. The fatty acid composition of kidney phospholipids was markedly affected by these diets. These results indicate that the renal injury observed in the groups fed safflower oil with a high n-6/n-3 ratio and rapeseed oil with presumed minor components is accompanied by increased expression of the TGF-beta, renin and fibronectin genes, and that dietary DHA suppresses renal injury and gene expression as compared with soybean oil.

Animals↗

Dietary docosahexaenoic acid but not eicosapentaenoic acid suppresses lipopolysaccharide-induced interleukin-1 beta mRNA induction in mouse spleen leukocytes.

Mice were fed a diet supplemented either with beef tallow (BT), BT plus ethyl eicosapentaenoate (EPA) or BT plus ethyl docosahexaenoate (DHA) for 9 weeks. EPA and DHA supplementation increased the content of the respective fatty acid in spleen leukocyte lipids, which was associated with the reduction in the arachidonate content. IL-1beta mRNA induction upon lipopolysaccharide (LPS) stimulation in spleen leukocytes in the DHA diet group was significantly lower than in the BT diet group, but the EPA diet was without any significant effect. The amount of prostaglandin E2 (PGE2) released from LPS-stimulated spleen leukocytes was significantly lower in both the EPA and DHA groups than in the BT group. Thus, dietary EPA and DHA inhibited arachidonate metabolism similarly but had different effects on IL-1beta mRNA induction in mouse spleen leukocytes.

Animals↗

Transperineal magnetic resonance image guided prostate biopsy.

PURPOSE: We report the findings of a transperineal magnetic resonance image (MRI) guided biopsy of the prostate in a man with increasing prostate specific antigen who was not a candidate for a transrectal ultrasound guided biopsy. MATERIALS AND METHODS: Using an open configuration 0.5 Tesla MRI scanner and pelvic coil, a random sextant sample was obtained under real time MRI guidance from the peripheral zone of the prostate gland as well as a single core from each MRI defined lesion. The patient had previously undergone proctocolectomy for ulcerative colitis and, therefore, was not a candidate for transrectal ultrasound guided biopsy. Prior attempts to make the diagnosis of prostate cancer using a transurethral approach were unsuccessful. RESULTS: The random sextant samples contained benign prostatic hyperplasia, whereas Gleason grade 3 + 3 = 6 adenocarcinoma was confirmed in 15% and 25% of the 2 cores obtained from the MRI targeted specimens of 2 defined lesions. The procedure was well tolerated by the patient. CONCLUSIONS: Transperineal MRI guided biopsy is a new technique that may be useful in detecting prostate cancer in men with increasing prostate specific antigen who are not candidates for transrectal ultrasound guided biopsy.

Adenocarcinoma↗

Chronic administration of docosahexaenoic acid improves reference memory-related learning ability in young rats.

Wistar rats were fed a fish oil-deficient diet through three generations. The young (five-week-old) male rats of the third generation were randomly divided into two groups. Over 10 weeks, one group was perorally administered docosahexaenoic acid dissolved in 5% gum Arabic solution at 300 mg/kg/day; the other group received a similar volume of vehicle alone. Five weeks after starting the administration, the rats were tested for learning ability related to two types of memory, reference memory and working memory, with the partially (four of eight) baited eight-arm radial maze. Reference memory is information that should be retained until the next trial. Working memory is information that disappears in a short time. Entries into unbaited arms and repeated entries into visited arms were defined as reference memory errors and working memory errors, respectively. Docosahexaenoic acid administration over 10 weeks significantly reduced the number of reference memory errors, without affecting the number of working memory errors, and significantly increased the docosahexaenoic acid content and the docosahexaenoic acid/arachidonic acid ratio in both the hippocampus and the cerebral cortex. In addition, the ratio demonstrated a significantly negative correlation with the number of reference memory errors. These results suggest that chronic administration of docosahexaenoic acid is conducive to the improvement of reference memory-related learning ability, and that the docosahexaenoic acid/arachidonic acid ratio in the hippocampus or the cerebral cortex, or both, may be an indicator of learning ability.

Animals↗

Dietary docosahexaenoic acid enhances ferric nitrilotriacetate-induced oxidative damage in mice but not when additional alpha-tocopherol is supplemented.

Weaning mice were fed a diet supplemented with beef tallow (BT) or BT plus docosahexaenoic acid (DHA) containing 100 mg alpha-tocopherol/kg (alpha-Toc100) or 500 mg alpha-tocopherol/kg (alpha-Toc500) for 4 wk to modify membrane fatty acid unsaturation, and then were administered ferric nitrilotriacetate (Fe-NTA). The mortality caused by Fe-NTA was higher in the group fed the DHA (alpha-Toc100) diet than in the BT diet groups but the DHA (alpha-Toc500) diet suppressed this increase. Serum and kidney alpha-tocopherol contents were slightly influenced by the dietary fatty acids but not significantly. These results indicate that the increased unsaturation of tissue lipids enhances oxidative damage induced by Fe-NTA in mice fed DHA (alpha-Toc100) but not when additional alpha-tocopherol is supplemented. The apparent discrepancy between the observed enhancement by dietary DHA of oxidative damage and the beneficial effects of dietary DHA on the so-called free radical diseases is discussed in terms of strong bolus oxidative stress and moderate chronic oxidative stress.

Animals↗

The hypotensive effect of docosahexaenoic acid is associated with the enhanced release of ATP from the caudal artery of aged rats.

Fish oils have been shown to lower blood pressure in hypertensive subjects. To determine the mechanism of this hypotensive effect, we examined the effects of docosahexaenoic acid (DHA), one of the (n-3) polyunsaturated fatty acids in fish oil, on blood pressure and on the release of adenyl purines, such as ATP, ADP, AMP and adenosine, from the caudal arteries of aged rats. Aged female Wistar rats (100 wk) were fed a high cholesterol diet and were administered intragastrically ethyl all-cis-4,7,10,13,16,19-docosahexaenoate [300 mg/(kg.d)] for 12 wk (DHA group) or vehicle alone (control group). Compared with the controls, rats supplemented with DHA had significantly greater (10.1%) DHA concentrations in the caudal arteries. This was associated with more total (n-3) arterial fatty acids, a greater unsaturation index of arterial fatty acids, 43.9% lower plasma noradrenaline levels and the repression of the elevation in blood pressure observed with advancing age. The amount of purines released, both spontaneously and in response to noradrenaline, from arterial segments of DHA-supplemented rats was significantly higher than that released from tissues of control rats. Regression analysis revealed significant negative relationships between the total amount of purines released from the artery and the systolic (SBP) and diastolic (DBP) blood pressures. These results suggest that in aged rats, supplementation with DHA alters the membrane fatty acid composition as well as the amount of ATP released from vascular endothelial cells and decreases plasma noradrenaline, and that these factors may ameliorate the rise in blood pressure normally associated with advancing age.

Adenosine Triphosphate↗

Positive feedback regulation of type I IFN genes by the IFN-inducible transcription factor IRF-7.

The interferon regulatory factor (IRF) family of transcription factors regulate the interferon (IFN) system, among which IRF-3 is involved in the virus-induced IFN-beta gene expression. Here we show that another member IRF-7 is critical for the IFN-alpha gene induction. Unlike the IRF-3 gene, the IRF-7 gene is induced by IFNs through activation of the ISGF3 transcription factor, and IRF-7 undergoes virus-induced nuclear translocation. In cells lacking p48, an essential component of IFN stimulated gene factor 3 (ISGF3), ectopic expression of IRF-7 but not IRF-3 can rescue the deficiency to induce IFN-alpha genes. These results indicate that IRF-7 is a key factor in the positive feedback regulation of IFN-alpha/beta production.

Amino Acid Sequence↗

Involvement of the IRF family transcription factor IRF-3 in virus-induced activation of the IFN-beta gene.

The virus-induced activation of interferon alpha/beta (IFN-alpha/beta) gene transcription is essential for host defense. The IFN-beta promoter is controlled primarily by the virus-inducible enhancer elements, the IRF-Es. Here we show that IRF-3, an IRF family transcription factor, translocates to the nucleus from the cytoplasm upon virus infection in NIH/3T3 cells. The nuclear IRF-3 is phosphorylated, interacts with the co-activators CBP/p300, and binds specifically to the IFN-beta IRF-E. Furthermore, overexpression of IRF-3 causes a marked increase in virus-induced IFN-beta mRNA expression. Thus, IRF-3 is a candidate transcription factor mediating the activation of the IFN-beta gene.

3T3 Cells↗

Correlation of plasma monocyte chemoattractant protein-1 (MCP-1) and monocyte inflammatory protein-1alpha (MIP-1alpha) levels with disease activity and clinical course of sarcoidosis.

MCP-1 and MIP-1alpha exhibit chemotactic activity toward macrophages/monocytes and induce the production of inflammatory cytokines affecting granuloma formation. Up-regulated expression of MCP-1 and MIP-1alpha in the affected organ of sarcoidosis has been shown; however, the relationship between their plasma levels and the clinical course of this disease has not been determined. In the present study we measured plasma MCP-1 and MIP-1alpha levels in 26 patients with active sarcoidosis by ELISA in order to assess the state of MCP-1 and MIP-1alpha in this disease. Most patients in this study (21/26) had clinical evidence of extrathoracic disease in addition to pulmonary involvement. In addition, a high proportion of patients (n = 15) showed spontaneous remission of disease, whereas five patients showed no spontaneous remission and six patients were treated with corticosteroids over the 2-year period of study. At the time of diagnosis, both plasma MCP-1 and MIP-1alpha levels in patients with active sarcoidosis were significantly higher than in the normal controls. The levels of these cytokines in patients with extrathoracic disease were compatible with those in patients without extrathoracic disease. A longitudinal evaluation of plasma MCP-1 and MIP-1alpha levels showed that the changes in both cytokines were closely related to the clinical course of sarcoidosis. These results suggest that plasma MCP-1 and MIP-1alpha may be useful parameters for monitoring the clinical course of sarcoidosis. In addition, plasma MCP-1 and MIP-1alpha may reflect subclinical evidence of extrathoracic sarcoidosis and may play a role in initiating monocyte migration into the tissue.

Adult↗

Effect of replacing a high linoleate oil with a low linoleate, high alpha-linolenate oil, as compared with supplementing EPA or DHA, on reducing lipid mediator production in rat polymorphonuclear leukocytes.

The fatty acid composition of rat polymorphonuclear leukocytes (PMN) was modified by diets supplemented with a high linoleate (LA) safflower oil (76% LA), mixtures of eicosapentaenoate (EPA) and safflower oil (EPA(20) containing 20% EPA and 61% LA, EPA(40) containing 40% EPA and 46% LA), mixtures of docosahexaenoate (DHA) and safflower oil (DHA(20) containing 20% DHA and 61% LA, DHA(40) containing 40% DHA and 46% LA) or a high alpha-linolenate (alpha-LNA) perilla oil (57% alpha-LNA and 13% LA), and then lipid mediator production in casein-induced peritoneal PMN were compared. EPA and DHA were relatively ineffective in reducing platelet-activating factor (PAF) production; a statistically significant reduction was observed only in the DHA(40) group. In contrast, perilla oil reduced PAF production by 50% as compared with safflower oil. Arachidonate (AA) in the PAF precursor, 1-alkyl-2-acyl-glycerophosphocholine, was roughly correlated with PAF production, but EPA and DHA in the precursor lipid were relatively unrelated. On the other hand, both PGE2 and LTB4 production correlated positively with AA and negatively with EPA and DHA in PMN phospholipids; EPA tended to be somewhat more effective than DHA in reducing PGE2 and LTB4 formation; the activity of perilla oil was no less than EPA(20). Thus, replacing safflower oil with perilla oil was no less effective than supplementing safflower oil with EPA or DHA (at 40% of total fatty acids) in reducing lipid mediator production in rat PMN.

Animals↗

Effect of dietary docosahexaenoic acid on in vitro thermogenesis and fatty acid compositions of brown adipose tissue.

Brown adipose tissue (BAT) is a major organ of nonshivering thermogenesis during cold acclimation, overfeeding, and nonthermal restraint stress. An increased unsaturation of fatty acids of membrane phospholipid in BAT has been shown to be closely associated with an enhanced function of this tissue as reported in other tissues. In the previous study, we found that among fatty acids detected, the n-3 polyunsaturated fatty acid docosahexaenoic acid (DHA) in BAT phospholipid is the only fatty acid that altered concomitantly with a change in the in vitro thermogenic capacity for nonshivering thermogenesis of BAT from cold acclimated and restrained rats. To examine the effect of dietary DHA on fatty acid composition of phospholipid and in vitro BAT thermogenic activity, rats were fed a standard diet supplemented with purified DHA for 4 or 16 weeks. Dietary DHA for 4 or 16 weeks increased DHA level in BAT phospholipid, and it also decreased arachidonic acid. The unsaturation index increased and remained unchanged under DHA feeding for 4 and 16 weeks, respectively. In vitro thermogenic activity of BAT remained unchanged and decreased under dietary DHA for 4 and 16 weeks, respectively. These findings indicate that dietary DHA could increase DHA level in phospholipid of BAT, but it could not improve in vitro BAT thermogenic response.

Acclimatization↗

Ameliorative effects of docosahexaenoic acid on serum lipid changes in stroke-prone spontaneously hypertensive rats.

It has been shown that docosahexaenoic acid (DHA) has numerous physiological actions. However, the precise mechanism of these actions is still obscure, and DHA is not yet regarded as a drug. The present study was undertaken to elucidate the effects of long-term administration of DHA on the serum lipid concentrations in stroke-prone spontaneously hypertensive rats (SPSHR). SPSHR was selected because serum lipid derangement is one of the primary risk factors in the development and maintenance of hypertension. DHA-treated SPSHR showed significantly lower blood pressure when compared with that of non-treated SPSHR; total cholesterol, triglyceride, low density lipoprotein and lipid peroxide levels were significantly decreased in DHA-treated SPSHR. On the other hand, the high density lipoprotein concentrations tended to increase in DHA-treated SPSHR when compared with those in non-treated SPSHR. These findings suggest that long-term administration of DHA has a protective effect against serum lipid derangement in SPSHR. This DHA-induced amelioration of serum lipid changes in SPSHR might be associated with mechanisms involving the antihypertensive action induced by DHA.

Animals↗

Docosahexaenoic acid inhibits blood viscosity in stroke-prone spontaneously hypertensive rats.

Increased blood viscosity facilitates the formation of thrombosis. This is an important risk factor in the occurrence of cerebral infarctions. The present study was undertaken to elucidate whether docosahexaenoic acid (DHA) inhibits blood viscosity, hematocrit and fibrinogen in the disease animal model, stroke-prone spontaneously hypertensive rats (SHRSP). An attempt was also made to clarify the effect of DHA on blood pressure in SHRSP. Blood viscosity, hematocrit and fibrinogen in non-treated SHRSP increased significantly when compared with levels in age-matched non-treated Wistar Kyoto rats (WKY). SHRSP rats which were administered DHA for 5 weeks displayed significant decreases in blood viscosity, hematocrit and fibrinogen when compared with the values in non-treated SHRSP. The blood pressure of DHA-treated SHRSP was significantly lower than that of non-treated SHRSP. A positive correlation existed between blood pressure and blood viscosity. These findings suggest that decreased blood viscosity induced by DHA appears to be associated with the reduction of thrombosis formation and hypotensive action in SHRSP.

Aging↗

Scalp localization using a simple algorithm.

We have developed a simple algorithm for scalp localization for craniotomy. Using a series of CT/MRI data, the point on the scalp closest to the center of the lesion (T) is determined by our program. A plane (plane R) is defined by three points: bilateral auditory meati and T. Point S is the intersection of three planes: the plane R, the scalp surface and the midsagittal plane. The distance from either S or the ipsilateral external auditory meatus to T is measured along the scalp surface on the plane R. The distance from the nasion to S along the scalp surface on the midsagittal plane is also measured. To determine the craniotomy site, these distances are measured directly on a patient's scalp in the operating room. This simple and accurate method for scalp localization could be used by installing our program in conventional CT/MR scanners.

Aged↗

[Cardiac disorders associated with progressive systemic sclerosis].

This study investigated cardiac disorders in 25 patients with diagnoses of progressive systemic sclerosis based on the criteria of the American College of Rheumatology. All were women, and the mean age was 59 +/- 11 (range 41-80) years old. The duration of the disease was 11 +/- 9 (range 3-40) years. The following complications were seen; Raynaud's phenomenon in all, esophageal disorders in 11, pulmonary fibrosis in 9, diabetes mellitus in 3, high blood pressure in 6, hyperlipidemia in 7, and positive anticardiolipin antibody in 8. Electrocardiography (ECG) and echocardiography were performed to assess the cardiac disorders. Abnormal ECG was seen in 11 patients (44%) and abnormal echocardiograms in 16 patients (64%). ECG abnormalities included incomplete right bundle branch block in 8 (32%), low voltage in 3 (12%), supraventricular arrhythmia in 3 (12%), ventricular arrhythmia in 1 (4%) and septal myocardial infarction pattern in 1 (4%). Echocardiographic abnormalities included valvular diseases in 13 (52%) and pericardial thickening in 7 (28%). No relationship was found between ECG and echocardiographic abnormalities. Echocardiographic abnormalities were more frequently observed in patients with positive anticardiolipin antibody (7/8, 88%) than in those with negative anticardiolipin antibody (9/17, 53%). Especially, pericardial thickening was seen in 63% (5/8) of positive patients, in comparison to 12% (2/17) of the negative patients (p < 0.05). Patients with progressive systemic sclerosis may have several cardiac disorders including conduction disturbances, low voltage ECG, valvular diseases and pericardial thickening. Pericardial thickening has a close relationship with positive anticardiolipin antibody.

Adult↗

Transcription of human ABO histo-blood group genes is dependent upon binding of transcription factor CBF/NF-Y to minisatellite sequence.

We have studied the transcriptional regulatory mechanism of the human histo-blood group ABO genes, and identified DNA cis-elements and trans-activating protein that control the expression of these genes which are important in blood transfusion and organ transplantation. We introduced the 5'-upstream sequence of ABO genes into the promoterless reporter vector and characterized the promoter activity of deletion constructs using transient transfection assays with gastric cancer cell line KATO III cells. The sequence just upstream of the transcription start site (cap site), and an enhancer element, which is located further upstream (between -3899 and -3618 base pairs (bp) from the transcription initiation site) and contains 4 tandem copies of a 43-bp repeat unit, were shown in gastric cancer cells to be responsible for the transcriptional activity of the ABO genes. DNA binding studies have demonstrated that a transcription factor, CBF/NF-Y, bound to the 43-bp repeat unit in the minisatellite. Functional importance of these CBF/NF-Y-binding sites in enhancer activity was confirmed by transfection experiments using reporter plasmids with mutated binding sites. Thus, transcriptional regulation of the human ABO genes is dependent upon binding of CBF/NF-Y to the minisatellite.

ABO Blood-Group System↗

Mesp2: a novel mouse gene expressed in the presegmented mesoderm and essential for segmentation initiation.

We isolated a novel bHLH protein gene Mesp2 (for mesoderm posterior 2) that cross-hybridizes with Mesp1 expressed in the early mouse mesoderm. Mesp2 is expressed in the rostral presomitic mesoderm, but down-regulated immediately after the formation of the segmented somites. To determine the function of MesP2 protein (MesP2) in somitogenesis, we generated Mesp2-deficient mice by gene targeting. The homozygous Mesp2 (-/-) mice died shortly after birth and had fused vertebral columns and dorsal root ganglia, with impaired sclerotomal polarity. The earliest defect in the homozygous embryos was a lack of segmented somites. Their disruption of the metameric features, altered expression of Mox-1, Pax-1, and Dll1, and lack of expression of Notch1, Notch2, and FGFR1 suggested that MesP2 controls sclerotomal polarity by regulating the signaling systems mediated by notch-delta and FGF, which are essential for segmentation.

Amino Acid Sequence↗