Biomedical subjects

T Miyazaki

Publications and source records attributed to T Miyazaki.

At least 163 records · Page 9Linked to original sources

PubMed1999

Susceptibility to neuroleptic malignant syndrome in Parkinson's disease.

OBJECTIVE: To determine susceptibility to neuroleptic malignant syndrome (NMS) in patients with PD in relation to central monoamine metabolism. METHODS: CSF levels of homovanillic acid (HVA), 3-methoxy-4-hydroxy phenyletilene glycol (MHPG), and 5-hydroxyindole acetic acid (5-HIAA) were assayed in 98 PD patients (mean age, 77.2 years), including 11 patients with a prior NMS-like episode, by high-performance liquid chromatography with electrochemical detection. RESULTS: Patients with a previous NMS-like episode had worse parkinsonian disability as measured by Hoehn & Yahr scale (3.7 +/- 0.8 versus 3.0 +/- 1.1; p = 0.038) and lower CSF HVA levels (20.9 +/- 17.3 versus 44.7 +/- 22.2 ng/mL; p = 0.001) compared to those without, despite similar age, disease duration, and daily dosages of antiparkinsonian drugs between groups. Logistic regression analysis showed that the CSF HVA level (p = 0.008), but not 5-HIAA level (p = 0.621), was significantly and independently related to NMS, and that the MHPG level (p = 0.070) was tendentially associated with the disorder. Odds ratios (95% confidence intervals) corresponding to 10 ng/mL increment in CSF HVA, MHPG, and 5-HIAA levels were 0.30 (0.13 to 0.73), 4.03 (0.89 to 18.2) and 1.29 (0.47 to 3.58), respectively. CONCLUSIONS: Central dopaminergic and possible noradrenergic activity contributes to NMS development in an elderly population of PD patients. Measuring CSF levels of monoamine metabolites may provide a means for identifying NMS susceptibility in PD patients.

Aged↗

PubMed1999

Anti-tumor activity of interleukin-2-producing tumor cells and recombinant interleukin 12 against mouse glioma cells located in the central nervous system.

Interleukin 12 (IL-12) exhibits anti-tumor activity in a variety of laboratory models. Although IL-12 itself activates strong anti-tumor activity, the combination of vaccine therapy with IL-2-transduced tumor cells and systemic rIL-12 has been shown to cure tumor-bearing mice more effectively than either rIL-12 or IL-2-transduced tumor vaccines alone. In the present study, regression of brain tumors established in naive mice was obtained by combined administration of an intratumoral injection of a single dose of IL-2-producing glioma cells (SR/IL-2 cells) and recombinant IL-12. Intraperitoneal rIL-12 administration substantially delayed the growth of s.c. inoculated gliomas, but not of gliomas located in the brain. Although vaccination with SR/IL-2 cells alone was not effective against s.c. inoculated gliomas, the combination therapy of vaccination with irradiated SR/IL-2 cells and systemic rIL-12 was more effective than rIL-12 alone. In our brain-tumor model, intratumoral administration of irradiated SR/IL-2 cells and of rIL-12 remarkably prolonged survival as compared with untreated mice. Efficacy was reduced when studies were performed in mice depleted of CD8+ cells or NK cells. Mice cured of their intracerebral tumors by combined administration of SR/IL-2 cells and rIL-12 demonstrated protective immunity upon rechallenge. In summary, the therapeutic potential for control of tumor growth by intratumoral administration of IL-2-producing glioma cells and rIL-12 may be useful in the development of treatment for patients with glioma.

Animals↗

PubMed1999

Increased susceptibility of thymocytes to apoptosis in mice lacking AIM, a novel murine macrophage-derived soluble factor belonging to the scavenger receptor cysteine-rich domain superfamily.

Apoptosis of cells must be regulated both positively and negatively in response to a variety of stimuli in the body. Various environmental stresses are known to initiate apoptosis via differential signal transduction cascades. However, induction of signals that may inhibit apoptosis is poorly understood, although a number of intracellular molecules that mediate inhibition of apoptosis have been identified. Here we present a novel murine macrophage-specific 54-kD secreted protein which inhibits apoptosis (termed AIM, for apoptosis inhibitor expressed by macrophages). AIM belongs to the macrophage scavenger receptor cysteine-rich domain superfamily (SRCR-SF), members of which share a highly homologous conserved cysteine-rich domain. In AIM-deficient mice, the thymocyte numbers were diminished to half those in wild-type mice, and CD4/CD8 double-positive (DP) thymocytes were strikingly more susceptible to apoptosis induced by both dexamethasone and irradiation in vivo. Recombinant AIM protein significantly inhibited cell death of DP thymocytes in response to a variety of stimuli in vitro. These results indicate that in the thymus, AIM functions in trans to induce resistance to apoptosis within DP cells, and thus supports the viability of DP thymocytes before thymic selection.

Amino Acid Sequence↗

PubMed1999

Angioma serpiginosum: a report of 2 cases identified using epiluminescence microscopy.

BACKGROUND: Angioma serpiginosum is a rare, acquired vascular lesion simulating purpura, and should be differentiated from purpuric dermatoses such as Henoch-Schonlein purpura. OBSERVATIONS: We report 2 cases of angioma serpiginosum examined using epiluminescence microscopy. Characteristic findings of angiomas ("red lagoons") were observed entirely or focally in these 2 cases, but not in 4 cases of Henoch-Schonlein purpura and a case of senile purpura. CONCLUSION: Epiluminescence microscopy is beneficial in distinguishing angioma serpiginosum from purpuric dermatoses.

Adolescent↗

PubMed1999

Accumulation of neurofilaments and SOD1-immunoreactive products in a patient with familial amyotrophic lateral sclerosis with I113T SOD1 mutation.

OBJECTIVE: To report neuropathologic features of argyrophilic inclusions in the anterior horn cells, motor cortex Betz cells, and neurons of the medullary reticular formation, spinal posterior horn, and Clarke column in a Japanese case of familial amyotrophic lateral sclerosis with I113T substitution in exon 4 of the copper-zinc superoxide dismutase (SOD1) gene. METHODS AND RESULTS: These inclusions were stained pale pink on the hematoxylin-eosin stain and dark on the Bielschowsky stain. They were positive for antibodies to phosphorylated neurofilaments, ubiquitin, and SOD1. On electron microscopy, they consisted of abundant intermediate filaments of 10 to 20 nm in diameter with disordered array indicating neurofilaments. CONCLUSION: These findings suggest that the I113T mutation induces accumulation of neurofilaments and SOD1 in the central nervous system neurons.

Aged↗

PubMed1999

AIM, a murine apoptosis inhibitory factor, induces strong and sustained growth inhibition of B lymphocytes in combination with TGF-beta1.

Lymphocyte proliferation is stimulated by differential combinations of various cytokines, antigens and adhesion molecules. However, mechanisms of negative regulation in lymphocytes are poorly understood despite their potential importance in controlling the balance of lymphocyte proliferation, particularly at inflammatory sites. We recently reported a novel murine soluble protein, termed AIM, which inhibits apoptosis of a variety of cell types including CD4/CD8 double-positive thymocytes. AIM is secreted specifically by macrophages and belongs to the macrophage scavenger receptor cysteine-rich domain superfamily. Here we show that in addition to the apoptosis-inhibitory effect, AIM induces strong, long-term inhibition of B lymphocyte proliferation in combination with transforming growth factor-beta1 (TGF-beta1 in vitro), resulting in almost complete block of proliferation and immunoglobulin secretion. The function of AIM as a cell growth inhibitor requires pretreatment of B cells with TGF-beta1 which appears to increase expression of the AIM receptor on the B cell surface. Thus B lymphocyte proliferation is dramatically down-regulated by sequential exposition to TGF-beta1 followed by AIM. Like many cytokines, AIM has different functions depending on the types of target cells and the combination with other cytokines.

Animals↗

PubMed1999

BamHI-SacI RFLP and Gm analysis of the immunoglobulin IGHG genes in the Northern Selkups (west Siberia): new haplotypes with deletion, duplication and triplication.

Gm immunoglobulin allotypes have been studied in 1157 individuals of seven Northern Selkup populations, which account for 80% of the entire population of this west Siberian tribe. This study confirms that the northern Selkup populations are a Caucasoid-Mongoloid hybrid. Restriction fragment length polymorphism (RFLP) analysis of the IGHG genes using double BamHI-SacI digests, performed on 475 DNA samples, allowed us to describe nine new BamHI-SacI haplotypes (BS47 to BS55), eight of them being characterized by IGHG gene deletion or duplication: G1 (BS49) or G4 (BS55) deletion, G4 duplication (BS51), GP-G2-G4 multigene deletion (BS50), duplication (BS48, BS53 and BS54) or triplication (BS52). A new rare Gm haplotype 15,16*;1,17;23 has been found associated with BS52. The BS51 haplotype characterized by a duplicated G4 gene (additional 7.85 kb G4 band identifying a new G4*C5 allele) was always found associated with the Gm 5*;3;23 haplotype. A high RFLP diversity has been observed for the Northern-Mongoloid haplotype Gm 15,16*;1,17;.. which was found (1) with the BS27 haplotype characterized by a 3-exon hinge G3 gene, (2) with two different GP-G2-G4 multigene duplications, BS53 and BS54 haplotypes, which differ by the size of the duplicated G4 genes, and (3) with the BS55 haplotype characterized by a G4 deletion. In the Northern Selkups, haplotypes with duplicated genes were observed at a higher frequency (24%) than haplotypes with deleted genes (6%).

Arctic Regions↗

PubMed1999

A study on the adsorption structure of an adhesive monomer for precious metals by surface-enhanced Raman scattering spectroscopy.

In order to clarify the role of a primer on the adhesion between dental precious metals and resin, surface-enhanced Raman scattering (SERS) technique has been applied to the structural analysis of the adhesive monomer, 6-(N-(4-vinylbenzyl)propylamino)-1,3,5-triazine-2, 4-dithione (VBATDT) adsorbed on colloidal Au surfaces. VBATDT is one of the major components of commercial primers. A mixture of a methanol solution of VBATDT and aqueous Au colloid was illuminated by the 647.1 nm line from a Kr ion laser to obtain the SERS. The most intense peak at 458 cm-1 due to C = S stretching in the Raman spectrum of solid VBATDT disappears completely in the SERS, while all the other peaks due to vinylbenzyl group vibrations remain unchanged. It suggests that some structural change occurs in VBATDT upon adsorption on Au which involves the C = S bonds and that the molecule undergoes thione-thiol-type tautomerization in the adsorption process. The SERS spectrum of a commercial primer containing VBATDT exhibits a similar spectral pattern. The present results lead us to conclude that some specific interactions exist between the sulfur atoms of VBATDT and Au surface to form chemical bond likes, which are effective to improve the bond strength between dental precious metals and resin. The ambivalent properties of the primer, chemical stability in storage and chemical affinity to Au, are also explained by the thione-thiol-type tautomerization of VBATDT on the basis of the spectroscopic evidence.

Adhesives↗

PubMed1999

A case study for wintertime observation of atmospheric particulates by an eye-safe laser radar.

Atmospheric particulates were monitored on a typical high concentration day in early winter in Osaka, Japan, using a compact and portable eye-safe laser radar system. The height of mixing layer was about 0.4 km at 8:00 and gradually increased to 0.8 km at 14:00. The development of the layer was in inverse proportion to the decrease of particulates near the ground surface. Analysis of particulates collected with high-volume air samplers showed that concentrations of elemental carbon (EC), lead and ammonium ion near the surface decreased significantly from morning to midday, while concentrations of sulfate, nitrate, sodium and calcium ions were almost constant. The results obtained in the preliminary study suggest that anthropogenic particulates such as EC and lead are on the rise with development of mixing layer from morning to midday.

Journal Article↗

PubMed1999

Butyltin residues in livers of humans and wild terrestrial mammals and in plastic products.

Butyltin compounds (BTs) including mono-(MBT), di-(DBT) and tributyltin (TBT) were determined in livers of humans and wild terrestrial mammals, such as raccoon dogs (Nyctereutes procyonoids) and monkeys (Macaca fuscata) from Japan. In addition, 22 samples of plastic products were analyzed. BT residues were detected in all the liver samples of humans and raccoon dogs, with concentrations of <360 ng/g wet wt, whereas concentrations in the liver of monkeys were either less than the detection limit or were only in trace levels. Elevated concentrations of BTs, particularly DBT (<140,000 ng/g) and MBT (<130,000 ng/g), were found in some plastic products, such as baking parchments made from siliconized paper and gloves made up from polyurethane. The results of a cooking test using the above baking parchment indicated the transfer of BTs to foodstuffs. These observations suggest expansion of BT contamination among terrestrial mammals. BT pollution from industrial appliances, such as plastic stabilizers and catalysts other than those of marine origin as antifouling agents, are suggested as alternative sources of exposure.

Journal Article↗

PubMed1999

Efficacy of NND-502, a novel imidazole antimycotic agent, in experimental models of Candida albicans and Aspergillus fumigatus infections.

In vitro and in vivo anti-Candida albicans and anti-Aspergillus fumigatus activities of NND-502, a new imidazole-antimycotic, were compared with those of fluconazole (FCZ), itraconazole (ITZ) and/or amphotericin B (AmB). NND-502 exhibited strong in vitro antifungal activity against both fungal species; its MIC against C. albicans was 1-4 times lower than that of FCZ, and its MIC against A. fumigatus was at least 60-2000 times lower than that of ITZ and AmB. In vivo antifungal treatments with each drug were initiated 1 h after inoculation in the experimental models, so that antifungal potential reflected prophylactic activity rather than therapeutic activity. The oral regimen of NND-502 in a murine model of systemic C. albicans infection was much less effective than that of FCZ. In vivo anti-A. fumigatus activity of oral NND-502 in a murine model of systemic infection was apparently superior to that of FCZ and ITZ in terms of prolonging survival. In addition to the murine model of systemic aspergillosis, intravenous NND-502 was shown to be highly effective in a rat model of pulmonary aspergillosis compared with intravenous AmB; 90% of animals survived at a dose of 2.5 mg/kg per day of NND-502 while only 30% of animals escaped death when 5 mg/kg per day of AmB was used. This potent efficacy of NND-502 was also confirmed in a sublethal challenge study in which the administration of the agent at a dose as low as 1.25 mg/kg per day resulted in the significant reduction of organisms in the lung; no comparable effect of AmB was found.

Amphotericin B↗

PubMed1999

Sleeping environments as risk factors of sudden infant death syndrome in Japan.

For the purpose of assessing the risk factors of the sleeping environment in SIDS, we performed a population-based, case-control study. Index cases comprised 56 SIDS cases which were diagnosed on the basis of autopsies during a period of 11 years at the Department of Legal Medicine, Faculty of Medicine, University of the Ryukyus. Control cases comprised infants who were examined at regional health centers for Infant Health Screening. The incidence of SIDS obtained was 0.25 per 1000 live births, which was comparable to that obtained in other districts having the established medical examiner's system. The proportion of prone sleeping was 81.0% and 38.3% in the SIDS and control groups, respectively, and an odds ratio was calculated as 10.4 (99% confidence interval, 3.9 to 37.6). This indicates that prone sleeping is a risk factor of SIDS, in Japan, as reported in various countries. Various kinds of bedclothes were used in this country, and our survey of bedclothes in the control revealed their improper use for infants to sleep, particularly with the prone position. In addition, the co-sleeping habit, which was not uncommon in Japan, seems to contribute to certain deaths of infants whose causes of death were controversial. In the investigation of SIDS, therefore, the sleeping environments, such as bedclothes and the co-sleeping habit, as well as the sleeping position should be taken into consideration as risk factors.

Journal Article↗

PubMed1999

Severe osteopetrosis, defective interleukin-1 signalling and lymph node organogenesis in TRAF6-deficient mice.

BACKGROUND: TRAF6, a member of the tumour necrosis factor receptor-associated factor family, was first identified as a transducer of CD40 and interleukin-1 receptor (IL-1R) signals based on the interaction of TRAF6 with the cytoplasmic tail of CD40 and with the IL-1R associated kinase in vitro. However, the functions of TRAF6 in vivo remain unidentified. RESULTS: We show that TRAF6-/- mice exhibit severe osteopetrosis and are defective in osteoclast formation. In vitro culture experiments revealed that osteoclast precursor cells derived from TRAF6-/- mice are unable to differentiate to functional osteoclasts in response to osteoclast differentiation factor (ODF). In bone marrow of TRAF6-/- mice, the number of sIgM+B220+ immature B cells is markedly reduced while the ratio of proB to preB cells is not affected. In contrast, development of thymocytes is not affected. Furthermore, TRAF6-/- mice are defective in lymph node organogenesis and IL-1 signalling in thymocytes. CONCLUSIONS: The results identify TRAF6 as an essential component of ODF signalling pathway, and also show that TRAF6 plays pivotal roles in immune and inflammatory systems in vivo.

Animals↗

PubMed1999

Critical role of the membrane-proximal, proline-rich motif of the interleukin-2 receptor gammac chain in the Jak3-independent signal transduction.

BACKGROUND: The interleukin-2 receptor (IL-2R) consists of three subunits, the IL-2Ralpha, IL-2Rbetac, and IL-2Rgammac chains. The essential role of the IL-2Rgammac cytoplasmic domain, consisting of 86 amino acids, in signal transmission has been well documented. Particularly, the carboxyl ter-minal region containing 48 amino acids. is essential for the association with and activation of the Jak3 protein tyrosine kinase. On the other hand, little is known about the role of the rest of the IL-2Rgammac cytoplasmic region consisting of the membrane-proximal 38 amino acids. RESULTS: We show that a truncated mutant form of IL-2Rgammac which lacks the membrane-distal 48 amino acids is still capable of inducing the activation of Jak1 and Stat3/Stat5 in the absence of Jak3 activation. This membrane-proximal region can also mediate the IL-2-induced tyrosine phosphorylation of the p85 subunit of phosphatidylinositol-3-kinase (PI3K). Furthermore, these signalling events are completely abrogated when mutations are introduced into the proline-rich motif in this region. CONCLUSIONS: In this study, we identified a Jak3-independent signalling pathway(s) from the membrane-proximal region of IL-2Rgammac. Our results indicate that the proline-rich motif in this region plays a critical role in this signalling pathway(s). The present study may provide further insight into the mechanism of cellular responses mediated by IL-2 and other cytokines which utilize the IL-2Rgammac for their signal transmission.

Amino Acid Sequence↗

PubMed1999

Inhibition of sterol 14 alpha-demethylation of Candida albicans with NND-502, a novel optically active imidazole antimycotic agent.

To investigate the mode of action of the newly synthesized optically active imidazole compound, NND-502, (-)-(E)-[4-(2, 4-dichlorophenyl)-1,3-dithiolan-2-ylidene]-1-imidazolylacetonit rile, its effect on ergosterol biosynthesis in cell-free extracts of Candida albicans was examined and compared with that of the (S)-enantiomer of NND-502 in addition to lanoconazole and bifonazole, both of which are clinically used for the treatment of dermatomycoses. NND-502 was found to interfere with ergosterol biosynthesis by inhibition of sterol 14alpha-demethylase, while no interference due to the (S)-enantiomer of NND-502 was found, indicating that the stereochemical orientation of the 2, 4-dichlorophenyl group plays an important role in the interaction with the enzyme. In terms of drug concentration exerting 50% inhibition of ergosterol biosynthesis, NND-502 was 2.5 and 28 times more effective than that of lanoconazole and bifonazole, respectively.

Antifungal Agents↗

PubMed1999

Genetic dissection of the complex pathological manifestations of collagen disease in MRL/lpr mice.

An MRL strain of mice bearing a Fas-deletion mutant gene, lpr, MRL/MpJ-lpr/lpr (MRL/lpr) develops collagen disease involving vasculitis, glomerulonephritis, arthritis and sialoadenitis, each of which has been studied as a model for polyarteritis, lupus nephritis, rheumatoid arthritis and Sjögren's syndrome, respectively. Development of such lesions seems dependent on host genetic background since the congenic C3H/HeJ-lpr/lpr (C3H/lpr) mice rarely develop them. To identify the gene loci affecting each lesion, a genetic dissection of these complex pathological manifestations was carried out. First, histopathological features in MRL/lpr, C3H/lpr, (MRL/lpr x C3H/lpr) F1 intercross, and MRL/lpr x (MRL/lpr x C3H/lpr) F1 backcross mice were analyzed. Genomic DNA of the backcross mice were subjected to association studies by Chi-squared analysis for determining which polymorphic microsatellite locus occurs at higher frequency among affected compared to unaffected individuals for each lesion. As a result, gene loci recessively associated with each lesion were mapped on different chromosomal positions. We concluded that each of these lesions in MRL/lpr mice is under the control of a different set of genes, suggesting that the complex pathological manifestations of collagen disease result from polygenic inheritance.

Animals↗

PubMed1999

Increased erythrocyte 3-DG and AGEs in diabetic hemodialysis patients: role of the polyol pathway.

BACKGROUND: 3-Deoxyglucosone (3-DG) accumulating in uremic serum plays an important role in the formation of advanced glycation end products (AGEs). To determine if 3-DG is involved in the formation of intracellular AGEs, we measured the erythrocyte levels of 3-DG and AGEs such as imidazolone and N epsilon-carboxymethyllysine (CML) in hemodialysis (HD) patients with diabetes. Further, to determine if the polyol pathway is involved in the formation of erythrocyte 3-DG and AGEs, an aldose reductase inhibitor (ARI) was administered to these patients. METHODS: The erythrocyte levels of sorbitol, 3-DG, imidazolone, and CML were measured in ten diabetic HD patients before and after treatment with ARI (epalrestat) for eight weeks, and were compared with those in eleven healthy subjects. 3-DG was incubated in vitro with hemoglobin for two weeks to determine if imidazolone and CML are formed by reacting 3-DG with hemoglobin. RESULTS: The erythrocyte levels of sorbitol, 3-DG, imidazolone, and CML were significantly elevated in diabetic HD patients as compared with healthy subjects. The erythrocyte levels of 3-DG significantly decreased after HD, but sorbitol, imidazolone or CML did not. The administration of ARI significantly decreased the erythrocyte levels of sorbitol, 3-DG and imidazolone, and tended to decrease the CML level. Imidazolone was rapidly produced in vitro by incubating 3-DG with hemoglobin, and CML was also produced, but less markedly as compared with imidazolone. CONCLUSION: The erythrocyte levels of 3-DG and AGEs are elevated in diabetic HD patients. The administration of ARI reduces the erythrocyte levels of 3-DG and AGEs, especially imidazolone, as well as sorbitol. Thus, 3-DG and AGEs, especially imidazolone, in the erythrocytes are produced mainly via the polyol pathway. ARI may prevent diabetic and uremic complications associated with AGEs.

Adult↗

PubMed1999

Oral adsorbent ameliorates renal TGF-beta 1 expression in hypercholesterolemic rats.

BACKGROUND: A spontaneously hypercholesterolemic Imai rat has recently been reported as a model of focal glomerulosclerosis that causes nephrotic syndrome followed by renal failure. This study was designed to determine if an oral adsorbent, AST-120, ameliorates renal lesions and TGF-beta 1 expression in the rats. METHODS: AST-120 was given orally to the Imai rats for 32 weeks, and renal function and pathology were compared between the AST-120-administered and control Imai rats. RESULTS: AST-120-administered rats showed significantly lower level of blood urea nitrogen, serum creatinine, urinary protein, serum total-cholesterol, serum triglyceride, and serum and urinary indoxyl sulfate, and significantly higher levels of serum albumin and creatinine clearance than control rats. AST-120 reduced the glomerular sclerosis index, interstitial fibrosis area, and the extent of glomerular lipid deposition. Immunohistochemistry demonstrated that AST-120 reduced the expression of transforming growth factor (TGF)-beta 1 and tissue inhibitor of metalloproteinase (TIMP)-1 as well as interstitial infiltration of macrophages in the renal cortex of the Imai rats. CONCLUSIONS: AST-120 prevented the progression of nephrotic syndrome and renal failure in the Imai rats by ameliorating glomerular sclerosis and interstitial fibrosis, accompanied with reduced expression of TGF-beta 1 and TIMP-1, and reduced infiltration of macrophages in the kidneys.

Administration, Oral↗