Search PubMed⌕ Search

Biomedical subjects

H Harada

Publications and source records attributed to H Harada.

At least 307 records · Page 17Linked to original sources
PubMed1996

Regulation of IFN-alpha/beta genes: evidence for a dual function of the transcription factor complex ISGF3 in the production and action of IFN-alpha/beta.

BACKGROUND: Efficient production of interferons (IFNs) in virally infected cells is an essential aspect of the host defence. The transcription factor complex ISGF3 (IFN-stimulated gene factor 3) was originally identified as a critical mediator of the IFN signal; it is formed upon IFN receptor (IFNR) stimulation and binds to ISREs (IFN-stimulated response elements) to activate IFN-inducible genes. It has recently been shown that the DNA binding component of ISGF3, p48 (ISGF3gamma) also binds to virus-inducible elements in the IFN-alpha/beta genes, suggesting a potential new role of p48 in IFN production. RESULTS: Primary cells from mice with a targeted disruption of the p48 gene show severe defects in virus-induced IFN-alpha/beta gene expression. A similar defect was also observed in cells lacking type I IFNR or Stat1, further demonstrating the role of IFN signalling in the induction of these IFN genes. ISGF3 in fact binds to the virus-inducible elements within the IFN-alpha/beta promoters. We also provide evidence showing that these elements are additionally controlled by an unidentified factor(s) which presumably triggers the primary phase of IFN gene induction. CONCLUSIONS: Our results demonstrate that the IFN signal transducing complex ISGF3 plays a crucial role in IFN production and suggest that ISGF3 may participate directly in the activation of IFN-alpha/beta promoters. This dual function of ISGF3 may insure the efficient operation of this cytokine system in the host defence.

Animals↗
PubMed1996

Transient increase in the level of mRNA for a germin-like protein in leaves of the short-day plant Pharbitis nil during the photoperiodic induction of flowering.

A cDNA corresponding to an in vivo labeled protein whose level increased during flower-inductive darkness in the cotyledon of the short-day plant Pharbitis nil Choisy cv. Violet was isolated and characterized. The deduced amino-acid sequence of the protein (designated PnGLP; P.nil germin-like protein) showed homology to that of a GLP of Sinapis alba, a leaf protein, the mRNA accumulation of which showing circadian oscillations. PnGLP mRNA was detected specifically in the cotyledon and leaf, in particular, in the young expanded cotyledon and leaf. Accumulation of PnGLP mRNA increased transiently during flower-inductive darkness and peaked at a time that corresponded approximately to the critical night length. This mRNA peak was reduced by a brief exposure to red light at the 8th hour of darkness. The level of PnGLP mRNA peaked about 10 h from the beginning of the dark period, whereas it was reported that the level of mRNA for GLP of a long-day plant S. alba increased about 14 h from the beginning of the light period. Thus, the different time courses of accumulation of the mRNAs for leaf-specific GLPs appear to reflect the differences in photoperiodic responses of each plant.

Amino Acid Sequence↗
PubMed1996

The gene for multiple familial trichoepithelioma maps to chromosome 9p21.

Multiple familial trichoepithelioma (MFT) is an autosomal dominant skin disease characterized by the presence of many small tumors predominantly on the face. To map the causative gene, we performed linkage analysis with microsatellite markers in three American families. We found a significant linkage of a gene for MFT to chromosome 9p2l. The maximum combined lod score was 3.31 at D9S171 at theta = 0. The disease locus was defined to a 4-cM region between IFNA and D9S126. Because several tumor suppressor genes including p16 and p15 have been mapped to this region, the gene for MFT may also be a tumor suppressor.

Chromosome Mapping↗
PubMed1996

Intron retention generates a novel isoform of the murine vitamin D receptor that acts in a dominant negative way on the vitamin D signaling pathway.

We identified and characterized a novel rat vitamin D receptor isoform (rVDR1), which retains intron 8 of the canonical VDR (rVDR0) during alternative splicing. In this isoform protein directed by the stop codon in this newly identified exon, a part of the ligand binding domain (86 amino acids) is truncated at the C-terminal end but contains 19 extra amino acids. The rVDR1 transcript was expressed at a level 1/15 to 1/20 of that of rVDR0 in the kidney and intestine in adult rats but not in embryos. The recombinant rVDR1 protein showed no ligand binding activity. Homo- and heterodimers of the recombinant rVDR0 and rVDR1 proteins bound to a consensus vitamin D response element (VDRE) but not to consensus response elements for thyroid hormone and retinoic acid. However, unlike rVDR0, rVDR1 did not form a heterodimeric complex with RXR on the VDRE. A transient expression assay showed that this isoform acted as a dominant negative receptor against rVDR0 transactivation. Interestingly, the dominant negative activities of rVDR1 differed among VDREs. Thus, the present study indicates that this new VDR isoform negatively modulates the vitamin D signaling pathway, through a particular set of target genes.

Alternative Splicing↗
PubMed1996

Epidemiology of Parkinson's disease in Yonago City, Japan: comparison with a study carried out 12 years ago.

A study of the prevalence of Parkinson's disease (PD) was conducted in a Japanese city in 1992, and the data compared with those of a similar study performed in 1980. On the prevalence day, April 1, 1992, a total of 156 patients (46 males and 110 females) were found to be living in the investigated area, which had a population of 132,315. The prevalence per 100,000 population was 117.9 (72.8 in males and 159.1 in females), and the incidence during the period 1989 through 1992 was 15.0 per 100,000 population per year. The age- and sex-adjusted prevalence per 100,000 population was 99.5 in 1992 and 103.9 in 1980, as calculated using the 1990 Japanese population as the standard. The age-adjusted prevalence in the population under 60 years of age and the incidence in those under 55 years of age in 1992 were lower than in those under 55 in 1980. These results revealed that changes in the age structure of the population were the main contributors to the increased incidence of PD.

Adolescent↗
PubMed1996

Effects of cooling portions of the head on human thermoregulatory response.

Seven healthy young male students participated in this study. Each subject sat on a chair in an anteroom at 25 degrees C for 30 min and then entered a climatic chamber, controlled at 40 degrees C and R.H. 50%, and sat on a chair for 90 min. Cooling of frontal portion including the region around the eyes (FC), occipital portion (OC), and temporal portion (TC) began after 50 min of entering. An experiment without head cooling (NC) was also made for the control measurement. Thermal comfort and thermal sensation were improved by head cooling, but response was the same regardless of portion cooled. Although rectal temperature, mean skin temperature and heart rate showed no significant effect due to head cooling, forearm skin blood flow (FBF), sweat rate (SR), and body weight loss (delta Wt) had a tendency to be depressed. FBF in FC and TC decreased during head cooling, but that in OC and NC did not change significantly, while SR in FC was depressed. delta Wt showed total sweating to decrease by FC and TC, and FC to have greater inhibitory effect on sweating than OC. Thermal strain was evaluated by the modified Craig Index (I(s)). I(s) in FC decreased significantly more than in NC. Cooling of other portions of the head had no significant effect on I(s). Cooling of the frontal portion of the head may thus be concluded to have the most effect on thermoregulatory response in a hot environment.

Acclimatization↗
PubMed1996

Abnormal desmoglein expression by squamous cell carcinoma cells.

Abnormal expression of cell adhesion molecules and related proteins has been observed in various carcinoma cells. We compared expression patterns of desmosomal cadherins, E-cadherin, and cytoplasmic plaque proteins of four different human squamous cell carcinoma cell lines and in vivo squamous cell carcinoma cells with those of normal human keratinocytes. Unlike normal human keratinocytes, the squamous cell carcinoma cells, both in culture and in vivo, exhibited diminished or unusual expression of desmoglein 3 and desmoglein 1, which bear pemphigus vulgaris and pemphigus foliaceus antigens, respectively. Abnormal expression of E-cadherin and cytoplasmic plaque proteins such as desmoplakin and plakoglobin was also observed. Western blotting study demonstrated that three squamous cell carcinoma cell lines expressed two desmogleins with a predominant 150 kDa molecule, and a minor 130 kDa one. Although these molecular sizes were similar to those of cultured normal human keratinocytes, the 130 kDa desmoglein, which usually carries pemphigus antigenic epitopes, was weakly or negatively reactive with pemphigus vulgaris serum. One squamous cell carcinoma cell line showed a doublet of 140 and 145 kDa bands in addition to the 130 kDa band. All the carcinoma cell lines constantly expressed desmoglein 2 and desmoglein 3 mRNA, whereas cultured normal human keratinocytes always expressed desmoglein 1 and desmoglein 3 mRNA, with or without desmoglein 2 mRNA. These findings indicate that the squamous cell carcinoma cells revealed abnormal expression of desmoglein isoforms, which may be related to tumor cell kinetics such as cell invasion and metastasis.

Antigens↗
PubMed1996

Oral cancer and hepatitis C virus (HCV): can HCV alone cause oral cancer?--a case report.

Previously, we reported the high prevalence of hepatitis C virus (HCV) infection in patients with oral cancer or oral lichen planus in Kyushu, Japan. We now report a 61-year-old man with chronic hepatitis C and no oral lesions who developed oral cancer 6 months after interferon therapy (interferon alpha [HLBI], 6 million units (MU) daily for 2 weeks and then 3 times a week for 14 weeks). This case emphasizes the need for periodic oral cavity examinations of hepatitis C patients and contributed to the investigation of oral cancer and HCV.

Hepacivirus↗
PubMed1996

[Surgical results of two cases of simultaneous carotid endarterectomy and coronary artery bypass grafting].

Reports on simultaneous revascularization operations for concomitant stenoses of the carotid and coronary arteries are many in Europe and America but few in Japan. Herein we report two cases of successful combined carotid endarterectomy and coronary artery bypass grafting. The first case was a 56-year-old male who had effort angina and a right carotid bruit with tinnitus. He was revealed to have severe stenosis of the right internal carotid artery as well as significant lesions of the right coronary artery. The second case was a 69-year-old male who had unstable angina and a left carotid bruit with a history of transient ischemic attack. Coronary angiography revealed three vessel disease and carotid digital subtraction angiography also revealed critical stenosis of the left internal carotid artery. In both cases, simultaneous carotid endarterectomy with an internal shunt and coronary artery bypass grafting were performed with a successful outcome. The use of internal shunt on reconstruction of the carotid artery was effective for protecting the brain.

Angina Pectoris↗
PubMed1996

[A case report of coronary artery bypass grafting in a patient with Sjögren's syndrome].

There have been very few reports on coronary artery bypass grafting (CABG) during collagen disease. This paper reports a 49-year-old female suffering angina after myocardial infarction who revealed preoperatively findings such as arthralgia, thrombocytopenia and positive anti-nuclear antibody. She underwent CABG and was definitely diagnosed as Sjögren's syndrome after the surgery. The coronary artery lesion in this case was mainly attributed to coronary arteritis due to Sjögren's syndrome because she was comparatively young and no other coronary artery risk factors such as hypertension, hyperlipidemia, thickened intima or angitis had been found by aortic pathology. Moreover, anticardiolipin antibody, which is highly related to the myocardial infarction in juveniles, was positive in this case.

Angina Pectoris↗
PubMed1996

[Microcirculatory disturbances after surgical insults--important role of inflammatory cytokines].

Microcirculatory disturbances in the gastric mucosa was investigated in rats after thermal injury using intravital video microscopy. Mucosal blood flow decreased significantly 5 hrs after thermal injury and increased neutrophil-endothelial cell interaction was observed at the same time. Zymosan stimulated-free radical production from peripheral blood was also increased and acute gastric mucosal lesion (AGML) appeared 5 hrs after thermal injury. These data suggest that neutrophil-endothelial cell interaction and increased free radical production induce AGML formation and that microcirculatory disturbance is one of the main reasons for organ failure after surgical insults. The role of inflammatory cytokines in hepatic microcirculatory disturbance was also studied in endotoxin-injected rats using IL-1 receptor antagonist (IL-1Ra) or TNF binding protein (TNFbp). Pretreatment with IL-1Ra or TNFbp significantly improved hepatic microcirculatory disturbance and reduced both the number of leukocytes adhered to the sinusoidal wall and the number of injured cells as well. These data suggest that inflammatory cytokines play a crucial role in microcirculatory disturbance after surgical insults by promoting neutrophil-endothelial cell interaction and systemic excessive inflammation.

Animals↗
PubMed1996

Fundamental study on the size and inter-key spacing of numeric keys for touch screen.

The purpose of this study was to reveal the optimum size and inter-key spacing of numeric square keys for touch screens. Six male students (22-25 years old) and three female students (21-24 years old) volunteered as subjects for this experiment. Each subject took part in data entry tasks using numeric square keys of touch devices. The sizes of keys were 6, 12, 21, 30 and 39 mm and each the inter-key spacing was 0, 3, 6, 12 and 21 mm. Response times with key sizes of 6 and 12 mm were significantly slower than with key sizes of 21 and 30 mm (p < 0.001). Furthermore, the key size of 6 mm significantly caused more errors than the key sizes of 12, 21, 30 and 39 mm (p < 0.05). The response time with inter-key spacing of 3 mm was significantly faster than with that of 0, 6, 12 and 21 mm (p < 0.001). Inter-key spacing of 0 mm significantly produced more errors than other inter-key spacing. Subjective ratings for inter-key spacing of 3, 6 and 12 mm were significantly better than those of 0 and 21 mm (p < 0.05). These results suggested that the optimum size of numeric square keys for touch screens should be more than 21 mm and optimum inter-key spacing should be from 3 to 6 mm. Optimum key size, however, must be selected with regard to the limitation of screen size.

Adult↗
PubMed1995

Activation of a cell-cycle-regulated histone gene by the oncogenic transcription factor IRF-2.

The human histone H4 gene FO108 is regulated during the cell cycle with a peak in transcription during early S phase. The cell-cycle element (CCE) required for H4 histone activation is a sequence of 11 base pairs that binds a protein factor in electrophoretic mobility shift assays that has been designated histone nuclear factor M (HiNF-M). Here we report the purification of HiNF-M, and show it to be a protein of relative molecular mass (M(r)) 48K that is identical to interferon (IFN) regulatory factor 2 (IRF-2), a negative transcriptional regulator of the IFN response. Recombinant IRF-2 (as well as the related protein IRF-1 (ref. 5)) binds the CCE specifically and activates transcription of this H4 histone gene. IRF-2 has been shown to have oncogenic potential, and our results demonstrate a link between IRF-2 and a gene that is functionally coupled to DNA replication and cell-cycle progression at the G1/S phase transition.

Animals↗
PubMed1995

A myosin missense mutation, not a null allele, causes familial hypertrophic cardiomyopathy.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is characterized by myocardial hypertrophy of unknown etiology. Missense mutations of the cardiac beta-myosin-heavy-chain (beta-MHC) gene that may be responsible for cardiac hypertrophy have been detected in patients with HCM. On the other hand, gross structural abnormalities in the cardiac beta-MHC gene, ie, an alpha/beta hybrid gene and partial deletion of the gene, have also been reported. The direct correlation between gross abnormalities and development of HCM is not well understood. METHODS AND RESULTS: We analyzed the structure of the cardiac beta-MHC gene from patients with HCM by using polymerase chain reaction-DNA conformation polymorphism analysis and found two sequence variations in exons 3 and 22 in one patient. These sequence variations at codon 54 (exon 3; nonsense mutation) and codon 870 (exon 22; Arg-to-His mutation) were identified by direct sequencing and dot-blot hybridization with allele-specific oligonucleotide probes. Relatives of this patient were examined for the mutations. It was revealed that the missense mutation was inherited from the affected father and the nonsense mutation from the unaffected grandmother through the unaffected mother. In addition, the missense mutation was also found in seven other patients from two other unrelated multiplex HCM families. CONCLUSIONS: The Arg870His mutation was suggested to cause HCM. In contrast, the gene with the nonsense mutation would encode for a cardiac beta-MHC protein of only 53 amino acid residues, which may be too short to be incorporated into the thick filament assembly of cardiac myosin chains and showed no dominant phenotype of heart disease. This is the first report of a nonsense mutation in the human cardiac beta-MHC gene.

Base Sequence↗