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Biomedical subjects

N Hata

Publications and source records attributed to N Hata.

At least 55 records · Page 3Linked to original sources

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↗

Development of a frameless and armless stereotactic neuronavigation system with ultrasonographic registration.

OBJECTIVE: We have developed a frameless stereotactic neuronavigation system that allows navigation during neurosurgical procedures through an image formed from integrating ultrasonography and preoperative magnetic resonance (MR) imaging and/or x-ray computed tomography. METHODS: The system consists of a ultrasound imaging scanner, a workstation with an image capture board, and an ultrasonic tracking sensor with a 5-MHz ultrasonographic transducer. The ultrasonic tracking sensor measures the position and orientation of the ultrasonographic transducer. The oblique plane of the MR/computed tomographic image corresponding to the ultrasound image is then displayed on the workstation monitor. A three-dimensional computer graphic representation of the integrated image is also reported as a preliminary test. For the patient-image registration, the coordinates of digitized and imaged markers on a specifically developed reference frame are used. The reference frame is noninvasive because it is not bolted but only fastened to the patient's head with silicon. RESULTS: Based on the findings from the clinical application of the system in three cases, the system was advantageous because of the surgical procedures could be controlled by intraoperative ultrasonography as well as by preoperative MR/computed tomographic images. Missing parts in the ultrasonogram were supplemented with preoperative MR/computed tomographic images. At other times, spatial positioning and visualization by ultrasonography were useful for identifying anatomical objects in the image. CONCLUSION: This preliminary study of the frameless integration of ultrasonography into stereotactic space demonstrated its clinical usefulness. We believe that the concept of pre- and intraoperative image-guided surgery presented here will find increasing use in the future.

Adolescent↗

Homicide patterns in the Toyama Prefecture, Japan.

Homicides occurring in the Toyama prefecture, Japan, during the past 10 years were reviewed. Between 1985 and 1994, 56 offenders committed 63 homicides. The mean death rate for homicide was 0.55 per 100,000. The ratio of male to female victims was 1:1, while 82% of the assailants were male and 18% were female. The victim and the assailant had a close family relationship in 58.7% of the cases. Dyadic death (homicide followed by suicide) accounted for 27% of all victims. Twenty-nine per cent of the victims were murdered by mentally unstable offenders, and in almost half (44%) of the cases the offender was convicted. Homicides during robbery were rare (only two cases), and there was only one homicide during sexual assault. Death was caused by blunt instrument injury in 38.1% of cases, asphyxia in 31.7%, stabbing in 17.5%, burns in 9.5% and shooting in 3.2% (only two cases). The majority (80%) of homicides occurred at the residence of the victim(s). None of the victims had a history of drug abuse. Social conditions in Toyama prefecture, and their possible relevance to local homicide patterns, are discussed briefly.

Adolescent↗

MesP1: a novel basic helix-loop-helix protein expressed in the nascent mesodermal cells during mouse gastrulation.

A subtractive hybridization strategy was used to isolate putative genes involved in the development of mouse primordial germ cells (PGC). Complimentary DNA was amplified on RNA isolated from the base of the allantois where PGC are located in the 7.5 days post coitum (dpc) mouse embryo. It was then subtracted by hybridization with cDNA amplified on RNA of the anterior region where PGC are absent. A novel gene thus isolated is designated as Mesp1 and encodes a possible transcription factor MesP1 containing a basic helix-loop-helix motif. Its earliest expression was observed at the onset of gastrulation, as early as 6.5 dpc, in the nascent mesodermal cells that first ingressed at the end of the primitive streak. These expressing cells in the lateral and extraembryonic mesoderm showed a wing-shaped distribution. Its initial expression was soon down-regulated at 7.5 dpc before the completion of gastrulation, except at the proximal end of the primitive streak which included the extraembryonic mesoderm and the base of allantois. At 8 dpc, the expression at the base of the allantois moved laterally. This distribution between 7.0 and 8.0 dpc was similar to that of PGC detected by the alkaline phosphatase activity. However, the expression of Mesp1 was down-regulated thereafter, when PGC entered in the migration stage. After birth, Mesp1 expression was detected only in mature testes, but in a different isoform from that expressed in the embryo. Mesp1 was mapped to the mid region of chromosome 7, near the mesodermal deficiency gene (mesd). However, a Southern hybridization study clearly showed that Mesp1 was distinctly different from mesd. The amino acid sequence and its expression pattern suggest that MesP1 plays an important role in the development of the nascent mesoderm including PGC.

Amino Acid Sequence↗

[Five cases of myelodysplastic syndrome treated with cytarabine ocfosfate].

Five cases of myelodysplastic syndrome were treated with cytarabine ocfosfate. Ocfosfate (100-200 mg) was orally administered for 14 days with 14 days' interval. Etoposide was combined in one case, and nartograstim was added in two cases. Two of the five cases achieved remission, one case having complete remission, and another case showing a good response. Their remission durations were 141 and 112 days, respectively. Further improvement of therapy is needed to achieve a higher remission rate and a longer remission duration.

Administration, Oral↗