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Biomedical subjects

Y Hirata

Publications and source records attributed to Y Hirata.

At least 91 records · Page 5Linked to original sources
PubMed2000

Immunotoxicity of N,N-diethylaniline in mice: effect on natural killer activity, cytotoxic T lymphocyte activity, lymphocyte proliferation response and cellular components of the spleen.

We previously found that N,N-diethylaniline increased the frequency of sister chromatid exchange (SCE) of human lymphocytes to about five times that of the control value, and was as toxic as cyclophosphamide used as a positive control for SCE. To explore whether N,N-diethylaniline affects the function of lymphocytes, we evaluated its immunotoxicity using CBA/N mice. The mice were divided into four groups and received 0, 100, 200, or 400 mg/kg body weight of N,N-diethylaniline by subcutaneous injection. The following items were investigated on days 3 and 7 after injection: body weight, weight of spleen, number of splenocytes, natural killer (NK) and cytotoxic T lymphocyte (CTL) activities, and concanavalin A (Con A)- and lipopolysaccharide (LPS)-stimulated lymphocyte proliferation using splenocytes. The following splenocyte phenotypes were also quantified by flow cytometry: (1) B cells; (2) total T cells; (3) CD4(+) and CD8(+) T cells; (4) NK; (5) macrophages and (6) nucleated erythrocytes. The splenic NK and CTL activities in exposed groups significantly decreased compared to the control in a dose-dependent manner and lymphocytes from the 200 and 400 mg/kg groups showed significantly higher spontaneous proliferation. The weight of the spleen and number of splenocytes were significantly higher in exposed groups than in the control. N,N-Diethylaniline also increased the percentages of macrophages, nucleated erythrocytes and B cells in the spleen. On the other hand, N,N-diethylaniline did not affect LPS-stimulated B cell and Con A-stimulated T cell proliferation, or the percentages of NK, total T, and CD4(+) and CD8(+) T cells in the spleen or the body weight of mice. The above findings indicated that N,N-diethylaniline selectively inhibited splenic NK and CTL activity and this inhibition was due to decreased NK and CTL functions, but not due to changes in the numbers of splenic NK and T cells.

Aniline Compounds↗
PubMed2000

Auditory cortex responds in 100 ms to incongruity of melody.

In order to find the cortical neural activities that reflect musical processing, we conducted measurements of MEG responses while subjects listened to familiar melodies. Significant enlargement of the N1m peak was observed in the response to the endnote of a phrase that was deviated to out-of-key from the keynote. Equivalent current sources of the enlarged N1m response were localized in the cortical area of the superior temporal plane. These results suggest the possibility of fast neural processing, as early as 100 ms, of the auditory cortex detecting incongruity of a melody.

Adult↗
PubMed2000

The by-products generated during sarin synthesis in the Tokyo sarin disaster induced inhibition of natural killer and cytotoxic T lymphocyte activity.

More than 5000 passengers on Tokyo subway trains were injured by the nerve gas, sarin and its by-products. Analysis of phosphor-carrying metabolites of sarin and its by-products in urine samples from the victims suggested that they were exposed not only to sarin, but also by-products generated during sarin synthesis, i.e. diisopropyl methylphosphonate (DIMP) and diethyl methylphosphonate (DEMP). We suspected genetic after-effects due to sarin by-products, thus, we checked the frequency of sister chromatid exchange (SCE) and found that SCE was significantly higher in the victims than in a control group, and that DIMP and DEMP significantly induced human lymphocyte SCE in vitro. In the present study, to explore whether DIMP and DEMP, which induced a high frequency of SCE of lymphocytes, also affected the lymphocyte functions, we examined the effect of DIMP and DEMP on splenic natural killer (NK) and splenic cytotoxic T lymphocyte (CTL) activity in mice, and NK activity of human lymphocytes in vitro. We found that DIMP and DEMP significantly inhibited NK and CTL activity in a dose-dependent manner. The inhibition induced by DIMP was stronger than that by DEMP. The effect of DIMP and DEMP on the splenic NK activity of mice was stronger than on the splenic CTL activity, and the human lymphocytes is more sensitive to DIMP and DEMP than the splenocytes of mice.

Animals↗
PubMed2000

Molecular cloning and characterization of a novel gene encoding limonoid UDP-glucosyltransferase in Citrus.

We isolated a cDNA clone encoding limonoid UDP-glucosyltransferase (limonoid GTase) from the albedo of Satsuma mandarin (Citrus unshiu Marc.) and investigated the contribution to limonoid glucoside accumulation in fruit. The isolated cDNA clone (CitLGT) was 1732 bp in length encoding 511 deduced amino acids with a predicted molecular mass of 57.5 kDa. The products of in vitro translation from an expression vector had the limonoid GTase activity. Southern blot analysis of genomic DNA indicated that CitLGT was present as a single copy gene in the Citrus genome. The amount of transcript corresponding to CitLGT mRNA changed the same way as the fluctuation of limonin glucoside content during fruit development of navel orange (Citrus sinensis Osb.). This indicates that the transcription of CitLGT regulates the conversion of limonoid aglycones to glucosides in citrus fruit.

Amino Acid Sequence↗
PubMed2000

Small-Angle X-Ray Scattering Studies on Nucleation Formation of Dextran Precipitation in the Presence of Boron.

In the present study, the nucleation formation process of dextran precipitation in the presence of boron was investigated by small-angle X-ray scattering (SAXS) techniques. The formation mechanism of aggregates or nuclei is very important in the initial step of crystallization. SAXS measurement is an excellent technique for observing these processes. The results of SAXS measurement suggest that boron, as a trace impurity, induces the aggregating of dextran molecules intermolecularly as a process in the nucleation formation of dextran precipitate nuclei and causes precipitation of dextran through an elongation process. These reactions occur readily at low boron concentrations. In fact, boron, which was detected at low levels in dextran solutions, was concentrated in the precipitates. Therefore, an aqueous solution of boron-free dextran should be resistant to precipitation. Copyright 2000 Academic Press.

Journal Article↗
PubMed2000

Reentry into the cell cycle of contact-inhibited vascular endothelial cells by a phosphatase inhibitor. Possible involvement of extracellular signal-regulated kinase and phosphatidylinositol 3-kinase.

Vascular endothelial cells are unique in that they exit from the cell cycle when they come into contact with each other. Although the phenomenon is called "contact inhibition," little is known about the cellular mechanisms involved. Here we show that the phosphatase inhibitor sodium orthovanadate (SOV) induced the reentry of contact-inhibited human umbilical vascular endothelial cells (HUVECs) into the cell cycle and that reentry was associated with activation of the extracellular signal-regulated kinase (ERK) and phosphatidylinositol 3-kinase (PI 3-K)/Akt pathways. SOV stimulated [(3)H]thymidine uptake of contact-inhibited HUVECs in a time- and dose-dependent manner. SOV-induced increase in [(3)H]thymidine uptake was significantly inhibited by the mitogen-activated protein kinase kinase inhibitor PD98059 and by the PI 3-K inhibitor LY294002. SOV also stimulated the expression of cyclin D1, cyclin E, and cyclin A, and the activity of CDK2 kinase, whereas it decreased the expression of p27(kip1). In marked contrast, growth media alone did not induce these changes. Furthermore, these SOV-induced changes were abolished by pretreatment with PD98059 and LY294002. SOV stimulated phosphorylation of ERK and Akt in contact-inhibited HUVECs, while growth media alone did not. This phosphorylation was associated with inhibition of phosphatase activity in the cells. Finally, overexpression of high cell density-enhanced protein tyrosine phosphatase 1 inhibited c-fos and cyclin A promoter activity. Taken together, our results suggest that in contact-inhibited HUVECs, increased phosphatase activity suppressed the ERK and PI 3-K/Akt pathways, resulting in exit from the cell cycle by down-regulation of cyclin D1, cyclin E, and cyclin A and by up-regulation of p27(kip1).

Animals↗
PubMed2000

The visual performance and metamorphopsia of patients with macular holes.

BACKGROUND: Most patients attain better visual acuity with the elimination of metamorphopsia after successful closure of a macular hole (MH) by vitrectomy. OBJECTIVE: To determine the presurgical visual function of eyes with an MH. METHODS: We examined 54 eyes of 51 patients with an idiopathic MH using the Amsler chart. We evaluated the types of subjective metamorphopsia and compared them with the clinical factors associated with MHs. In a prospective study, we performed a montage test on a separate group of 16 patients with unilateral idiopathic MHs. The patients were asked to choose, while viewing with their better eye, the computer-modified picture that best matched the unmodified image seen by the eye with the MH. RESULTS: From the results of the Amsler chart test, we divided the subjective changes into 2 types of metamorphopsia; of the 54 eyes, pincushion distortion (bowed toward the center) was found in 33 (61%), and unpatterned distortion (no specific pattern) was found in 21 (39%). Pincushion distortion was significantly associated with an MH of shorter duration (< or =6 months) (P = .03) and an early stage (stage 2) of MH formation (P = .02). A scotoma was hard to detect, and patients had difficulty describing their scotomata and distortions. In the montage test, patients with early MHs chose portraits modified with a pincushion type of distortion. CONCLUSIONS: We found concentric pincushion metamorphopsia without subjective scotomata, which we suggest arises from an eccentric displacement of the photoreceptors. This accounts for the main characteristic of the visual performance of patients with idiopathic MHs.

Aged↗
PubMed2000

A mouse model of vascular injury that induces rapid onset of medial cell apoptosis followed by reproducible neointimal hyperplasia.

Genetically modified mice serve as a powerful tool to determine the role of specific molecules in a wide variety of biological phenomena including vascular remodeling. Several models of arterial injury have been proposed to analyze transgenic/knock-out mice, but many questions have been raised about their reproducibility and physiological significance. Here, we report a new mouse model of vascular injury that resembles balloon-angioplasty. A straight spring wire was inserted into the femoral artery via arterioctomy in a small muscular branch. The wire was left in place for one minute to denude and dilate the artery. After the wire was removed, the muscular branch was tied off and the blood flow of the femoral artery was restored. The lumen was enlarged with rapid onset of medial cell apoptosis. While the circumference of the external elastic lamina remained enlarged, the lumen was gradually narrowed by neointimal hyperplasia composed of smooth muscle cells. At 4 weeks, a concentric and homogeneous neointimal lesion was formed reproducibly in the region where the wire had been inserted. Similar exuberant hyperplasia could be induced in all strains examined (C57BL/6J, C3H/HeJ, BALB/c, and 129/SVj). This model may be widely used to study the molecular mechanism of post-angioplasty restenosis at the genetic level.

Angioplasty, Balloon↗
PubMed2000

S-Methylisothiourea sulfate improves renal, but not hepatic dysfunction in canine endotoxic shock model.

OBJECTIVE: Excess production of nitric oxide (NO) by inducible NO synthase (iNOS) has been implicated in the pathophysiology of septic shock. This study was designed to see whether S-methylisothiourea sulfate (SMT), a selective inhibitor for iNOS, prevents cardiovascular changes and multiple organ damage in the canine endotoxic shock model. DESIGN: Prospective, comparable, experimental study. SETTING: Laboratory at a university hospital. SUBJECTS: Twenty male mongrel dogs were studied under pentobarbital anesthesia. INTERVENTIONS: Dogs were divided into three groups: bacterial lipopolysaccharide (LPS) group (n = 7) receiving continuous infusion of LPS (2 mg/kg/h for 1 h); LPS plus SMT group (n = 7) receiving LPS and SMT (1 mg/kg, bolus i. v., followed by continuous infusion of 1 mg/kg/h for 1 h); and vehicle plus SMT group (n = 6). MEASUREMENTS AND RESULTS: Hemodynamics, blood gas parameters, and urine output were measured during 6 h observation periods. Serum levels of lactate, transaminases, and bilirubin were measured at baseline, 1 and 6 h. Creatinine and free water clearance, urine sodium excretion and fractional excretion of sodium were calculated. LPS caused a profound hypotension associated with decreases in cardiac output and oxygen delivery, lactic acidosis, renal and liver dysfunction, and thrombocytopenia. SMT prevented the LPS-induced hypotension and renal dysfunction, whereas it did not affect the LPS-induced decreases in cardiac output or oxygen delivery, hyperlactatemia, liver dysfunction, or thrombocytopenia. SMT alone had no appreciable effects on hemodynamics, blood gases, liver or renal functions. CONCLUSIONS: These findings show that SMT improves renal, but not hepatic dysfunction, in dogs with endotoxic shock, suggesting that iNOS-derived NO plays differential roles in sepsis-associated multiple organ dysfunction.

Animals↗
PubMed2000

Degeneration of the cerebellar dentate nucleus in corticobasal degeneration: neuropathological and morphometric investigations.

To resolve the controversy regarding the involvement of the dentate nucleus in corticobasal degeneration (CBD), an entire profile of the dentate nucleus was exposed in a sagittal plane and divided into four fields, and the number of neurons in each filed was counted separately using a computer-assisted analyzer in five cases of CBD and compared to those from seven age-matched controls. The size of the nucleus and the number of neurons were significantly reduced in all five cases of CBD. The neuronal loss had a definite regional predilection, more severe in the caudolateral neodentatum than in the rostromedial palaeodentatum, and was accompanied by grumose degeneration and astrogliosis which paralleled the severity of the neuronal loss. Thus, the dentate nucleus appears to be a cardinal target in CBD.

Aged↗
PubMed2000

Solitary osseous hemangioma outside the spinal and craniofacial bones.

Bone hemangioma is mainly seen in the skull and spine, and rarely occurs in other bones. We report herein four cases of osseous hemangioma arising in rare sites: In two cases, on a rib; a faintly painful mass in one case located on the scapula; and progressive pain in one case located on the ischium. The tumors presented clinically as incidental lesions on radiographs. All cases had an aggressive appearance, such as defect of the cortex, a soft-tissue mass, and a sunburst-like appearance. Markedly high signal intensity on T2-weighted magnetic resonance images was a characteristic finding. Open biopsy resulted in severe blood loss, but needle biopsy was performed safely under computed tomography guidance. It is important to note that bone hemangiomas may be misdiagnosed as malignant tumors.

Adolescent↗
PubMed2000

Intra-abdominal metastases in musculoskeletal sarcomas.

This study examined the incidence, histological type, clinical symptoms, and prognosis in patients with intra-abdominal metastases of musculoskeletal sarcomas. The medical records of 505 patients with musculoskeletal sarcomas were reviewed for examples of intra-abdominal metastases. The incidence of intra-abdominal metastases (excluding lung) was: 4% in the liver (20 patients), 1.2% in gastrointestine (6 patients), 0.8% in pancreas (4 patients), and 0.8% on the peritoneal surface (4 patients). Patients with a previous hisory of lung metastases and those with high-grade liposarcoma tended to show metastasis in the intra-abdominal organs. Most patients with liver metastasis had no symptoms. Patients with gastrointestinal metastasis had abdominal pain, anemia, and melena. Patients with pancreatic metastasis had diabetes and jaundice. Six patients underwent surgical treatment, and two of them survived for more than 2 years. Metastases within the abdomen must be considered as a possible site for dissemination of musculoskeletal sarcomas, especially in patients with advanced disease and those with liposarcoma.

Adolescent↗
PubMed2000

Analysis of the discharge pattern of floccular Purkinje cells in relation to vertical head and eye movement in the squirrel monkey.

Purkinje (P) neurons are highly irregular in their discharge patterns having a high coefficient of variation. We have developed a method to extract the signal from these noisy neurons employing multiple linear regression against the input signals that are causal in P-cell firing, namely retinal slip, head motion parameters, and the efference copy of the oculomotor commands. This method was shown to extract all of the experimental stimulus-related signal as the residual following extraction had the same amplitude distribution and spectral content as those of the spontaneous discharge of P-cells when no external stimuli were applied. The method enables us to decompose P-cell firing modulation into components mediated by mossy fiber inputs to flocculus, that is, retinal slip, vestibular and oculomotor efference copy signals. By evaluating these components in relation to VOR adaptation, one can argue that one role of the flocculus is in converting these sensory and efference copy input signals into eye movement-related signals in conjunction with VOR motor learning.

Action Potentials↗
PubMed2000

Worldwide differences in the incidence of insulin autoimmune syndrome (Hirata disease) with respect to the evolution of HLA-DR4 alleles.

The relationship between the geographic distribution of susceptibility genes to insulin autoimmune syndrome (IAS) and the incidence of insulin autoimmune syndrome was investigated in order to examine the distribution of the genetic background to susceptibility to certain diseases. The HLA-DR4 allele, DRB1*0406, is associated with increased susceptibility to IAS among Japanese, while the DRB1*0403 and DRB1*0407 alleles are not (the odds ratio of which are 1.6 and 1.1, respectively). The worldwide geographic distribution of the three DR*04 alleles showed that the distribution of DRB1*0403 encompassed that of DRB1*0406 and DRB1*0407. Taken together with the findings that Glu at position 74 in the DRB1 molecule is shared by the three DRB1*04 alleles, there are only a few differences between the DRB1 molecule-nucleotide sequences of DRB1*0403, DRB1*0406 and DRB1*0407, and that all the three DRB1*04 alleles are carried by the same class II haplotype, DQA1*0301/DQB1*0302, it may be considered that DRB1*0403 is the ancestral allele of DRB1*0406 and DRB1*0407. Therefore, populations with a higher prevalence of DRB1*0406 have a higher risk of developing IAS. The extremely low prevalence of IAS among Caucasians can be explained by the low prevalence of DRB1*0406 in this population. This is a good example of the association between the predisposition to risk of development of certain diseases and the evolution of susceptibility genes.

Alleles↗
PubMed2000

Calcium supplement necessary to correct hypocalcemia after total parathyroidectomy for renal osteodystrophy.

BACKGROUND: Prediction of the extent of calcium supplement will facilitate safe and efficient management of hypocalcemia in the early postoperative stage of total parathyroidectomy with autotransplantation (PTXa) in patients with renal osteodystrophy. METHODS: The correlation between the extent of calcium deficiency, estimated by the amount of calcium supplement over 48 h after PTXa and using various parameters such as carboxy terminal parathyroid hormone (c-PTH), intact PTH (i-PTH), alkaline phosphatase (ALP), serum calcium, serum phosphorus, duration of hemodialysis, total weight of resected parathyroid glands and degree of subperiosteal resorption of the middle phalanx was examined in 49 patients who underwent PTX with subcutaneous autotransplantation. Bone mineral density (BMD) was also determined before, 3 months and 1 year after PTXa with dual energy X-ray absorptiometry (DEXA) in 13 patients. RESULTS: There was a positive correlation between pre-operative i-PTH level (r=0.56, P<0.0005) or ALP level (r=0.50, P<0.0005) and the amount of calcium supplement over 48 h after PTXa in these patients. Furthermore, the degree of subperiosteal resorption, determined by Jensen's classification, was significantly correlated with the amount of calcium supplement after PTX (P<0.05). Bone mineral density 3 months after (P<0.0005) and 1 year after PTXa (P<0.001) significantly increased compared with BMD before PTXa in all patients examined. CONCLUSION: These findings suggest that the pre-operative determination of i-PTH, ALP levels and degree of subperiosteal resorption allow the management of hypocalcemia safely and efficiently in renal osteodystrophy patients after PTXa.

Adult↗
PubMed2000

H. pylori activates NF-kappaB through a signaling pathway involving IkappaB kinases, NF-kappaB-inducing kinase, TRAF2, and TRAF6 in gastric cancer cells.

BACKGROUND & AIMS: H. pylori infection on gastric epithelial cells has been shown to induce NF-kappaB activation, but the mechanism of intracellular signal conduction that leads to NF-kappaB activation is not clear. The aim of this study was to analyze the molecular mechanism responsible for H. pylori-mediated NF-kappaB activation on gastric cancer cells. METHODS: NF-kappaB activation by H. pylori was tested by using luciferase reporter assay. IkappaBalpha degradation by H. pylori infection was assessed by immunoblotting. IKKalpha and IKKbeta activation was analyzed by kinase assay. In transfection experiments, effects of dominant negative IkappaBalpha, IKKalpha, IKKbeta, NF-kappaB-inducing kinase (NIK), TRAF2, and TRAF6 mutants were investigated. The effects of an IKKbeta-specific inhibitor, aspirin, on NF-kappaB activation and IL-8 secretion were also analyzed. RESULTS: H. pylori promotes degradation of IkappaBalpha, a cytoplasmic inhibitor of NF-kappaB. In kinase assay, H. pylori induced IKKalpha and IKKbeta catalytic activity in gastric cancer cells. Transfection of kinase-deficient mutant of either IKK inhibited H. pylori-mediated NF-kappaB activation dose-dependently. Aspirin inhibited both NF-kappaB activation and IL-8 secretion induced by H. pylori. NF-kappaB activation was also inhibited by transfection of kinase-deficient NIK or a dominant negative mutant of upstream adapter protein TRAF2 or TRAF6. CONCLUSIONS: H. pylori induces NF-kappaB activation through an intracellular signaling pathway that involves IKKalpha, IKKbeta, NIK, TRAF2, and TRAF6.

Aspirin↗
PubMed2000

Established histological identity and cell destruction treatments for cancer.

During cancerous cell turnover activity maintained by two types of mitosis, maturation and heteroduplication, cancer tissue consists of two types of cells, maturable and non-maturable. Most of the tissue is composed of maturable cells, which eventually disappear in the terminally matured cell phase. These cells do not participate in cell turnover activity or the organoid identity of cancer tissue. However, a small portion of the tissue is comprised of non-maturable cells, which replicate themselves endlessly, while producing maturable cells through each mitotic division in hetero-duplication mitosis. Thus, cell turnover activity and organoid identity are established in the cancer tissue. This organoid identity is solely responsible for carcinogenesis. Since most typical features of cancer are only detectable in maturable cells during maturation mitosis, cell destruction targeting these features should not be regarded as eradication. To eradicate cancer, the organoid identity of cancer, which is only established by heteroduplication mitosis, should clearly be recognized, and a new concept of cancer treatment based on destruction of the organoid identity should be devised in the future. This does not appear to be an insurmountable task.

Cell Differentiation↗