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Biomedical subjects

T Yasuda

Publications and source records attributed to T Yasuda.

At least 181 records · Page 10Linked to original sources
PubMed1999

Sjögren's syndrome in mice carrying the Ipr(cg) gene and the therapeutic efficacy of an immunosuppressive agent FK506.

The influence of the Ipr(cg) gene on the development of Sjögren's syndrome was followed up to 5 months of age in male and female mice of MRL, CBA and C3H strains. In MRL-Ipr(cg) mice, focal mononuclear cell infiltration started at 2 months and became conspicuous after 3 months of age in the lacrimal and submandibular glands but was minimal in the parotid and sublingual glands, even at 5 months of age, without any apparent sex effects found. In CBA and C3H mice carrying the Ipr(cg) gene, this manifestation of Sjögren's syndrome was much less prominent, indicating that the participation of some genes of the MRL strain may be indispensable for the development of Sjögren's syndrome in mice carrying this gene. In MRL-Ipr(cg) mice, an immunosuppressive agent, FK506, improved the serological abnormalities (decreased levels of anti-double-stranded DNA antibody of IgG2a and IgG3 subclasses) and proteinuria. It also reduced the manifestations of Sjögren's syndrome when it was intraperitoneally administered three times weekly at a dose of 2 mg/kg from 6 weeks (before disease onset) until 5 months of age (the termination of the experiment). Although VP8.2+ T cells have been demonstrated to be responsible for causing several autoimmune diseases, the selective deletion of Vp8.2+ T cells with the superantigen encoded by mouse mammary tumor virus did not affect the disease severity at all, suggesting that this T cell repertoire may not play a crucial role in induction of Sjögren's syndrome.

Animals↗
PubMed1999

Collagen secretion and growth of mesangial cells require geranylgeranylpyrophosphate.

BACKGROUND: The mevalonate pathway is important for the biosynthesis of isoprenoids such as geranylgeranylpyrophosphate (GGPP) and farnesylpyrophosphate, as well as cholesterol. It has been reported that treatment with 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor ameliorates glomerular injury in several experimental models of progressive glomerular disease. However, the effect of HMG-CoA reductase inhibitor on mesangial cell function has not been fully understood. This investigation was performed to elucidate the role of a mevalonate metabolite(s) in mesangial cell proliferation and extracellular matrix accumulation. METHODS: Cycling or quiescent human mesangial cells were incubated in RPMI 1640 containing 10% heat-inactivated fetal calf serum (FCS) in the absence or presence of pravastatin, an inhibitor of HMG-CoA reductase, and mevalonate metabolites. Type IV collagen secretion, mRNA expression, and [3H]thymidine incorporation were measured. Cell cycle phases were monitored by flow cytometry. RESULTS: Pravastatin inhibited FCS-stimulated type IV collagen secretion (IC50 = 210 microM) and mRNA expression. Pravastatin also inhibited FCS-stimulated [3H]thymidine incorporation (IC50 = 430 microM). Analysis with flow cytometry revealed that pravastatin inhibited the G1 to S phase transition of FCS-stimulated mesangial cells. Mevalonate reversed these inhibitory effects of pravastatin completely. Among two major metabolites of mevalonate, GGPP and farnesylpyrophosphate, only GGPP reversed pravastatin-induced inhibition of type IV collagen secretion, DNA synthesis, and the G1 to S phase progression. CONCLUSIONS: These results suggest that GGPP plays critical roles for the type IV collagen secretion and G1 to S phase transition in FCS-stimulated human mesangial cells.

Animals↗
PubMed1999

Effect of pravastatin on type IV collagen secretion and mesangial cell proliferation.

BACKGROUND: The mevalonate pathway is important for the biosynthesis of isoprenoids such as geranylgeranylpyrophosphate (GGPP) and farnesylpyrophosphate (FPP) as well as cholesterol. It has been reported that treatment with 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor ameliorates glomerular injury in several experimental models of progressive glomerular disease. The present investigation was performed to elucidate the role of mevalonate metabolites in mesangial cell proliferation and extracellular matrix accumulation. METHOD: Cycling or quiescent human mesangial cells were incubated in RPMI1640 containing 10% heat-inactivated fetal calf serum (FCS) in the absence or presence of pravastatin, an inhibitor of HMG-CoA reductase, and mevalonate metabolites. Type IV collagen secretion and mRNA expression, [3H]-thymidine incorporation was measured. Cell cycle phases were monitored by flow cytometry. RESULTS: Pravastatin inhibited FCS-stimulated type IV collagen secretion (IC50 = 210 microM) and mRNA expression. Pravastatin also inhibited FCS-stimulated [3H]-thymidine incorporation (IC50 = 430 microM). Analysis with flow cytometry revealed that pravastatin inhibited G1 to S phase transition of FCS-stimulated mesangial cells. Mevalonate reversed these inhibitory effects of pravastatin completely. Among two major metabolities of mevalonate, GGPP and FPP, only GGPP reversed pravastatin-induced inhibition of type IV collagen secretion, DNA synthesis and G1 to S phase progression. CONCLUSION: The present results suggest that GGPP plays a critical role in the type IV collagen secretion and G1 to S phase transition in FCS-stimulated human mesangial cells.

Cell Cycle↗
PubMed1999

Pituitary abscess secondary to isolated sphenoid sinusitis.

Intracranial complications from isolated sphenoid sinusitis are rare but nevertheless demonstrate both a high morbidity and mortality. We herein report a case of a pituitary abscess secondary to sphenoid sinusitis in a 12-year-old boy. This patient presented with an acute onset of moderate fever and headache, followed by progressive right ptosis. An emergency endoscopic endonasal sphenoidotomy with sinus drainage and postoperative antibiotic therapy resulted in a satisfactory recovery.

Brain Abscess↗
PubMed1999

Localization of a gene for benign adult familial myoclonic epilepsy to chromosome 8q23.3-q24.1.

Benign adult familial myoclonic epilepsy is an autosomal dominant idiopathic epileptic syndrome characterized by adult-onset tremulous finger movement, myoclonus, epileptic seizures, and nonprogressive course. It was recently recognized in Japanese families. In this study, we report that the gene locus is assigned to the distal long arm of chromosome 8, by linkage analysis in a large Japanese kindred with a maximum two-point LOD score of 4.31 for D8S555 at recombination fraction of 0 (maximum multipoint LOD score of 5.42 for the interval between D8S555 and D8S1779). Analyses of recombinations place the locus within an 8-cM interval, between D8S1784 and D8S1694, in which three markers, D8S1830, D8S555, and D8S1779, show no recombination with the phenotypes. Although three other epilepsy-related loci on chromosome 8q have been recognized-one on chromosome 8q13-21 (familial febrile convulsion) and two others on chromosome 8q24 (KCNQ3 and childhood absence epilepsy)-the locus assigned here is distinct from these three epilepsy-related loci. This study establishes the presence of a new epilepsy-related locus on 8q23.3-q24.11.

Adolescent↗
PubMed1999

A spectrum of clinicopathological features of nephropathy associated with POEMS syndrome.

BACKGROUND: In POEMS syndrome, substantial involvement of the kidney can occur and is reflected by proteinuria, haematuria, renal dysfunction, and renal failure requiring dialysis therapy. The mechanism by which renal dysfunction is induced and progresses to end-stage renal disease remains obscure. A pathogenic role of cytokines and growth factors has recently been implicated. METHODS: We reviewed cases of 52 Japanese patients with confirmed renal pathology who were reported in the literature, and personally analysed renal tissues from 22 subjects including nine patients of our own. Interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF) were measured in our cases. RESULTS: Despite relatively mild renal symptomatology, about half of the cases had azotaemia with creatinine levels above 1.5 mg/dl and the BUN/creatinine ratio markedly raised by volume contraction or wasting. One-tenth of patients were placed on haemodialysis because of advanced or end-stage renal disease. Bilateral and unilateral contracted kidneys were found in four and two cases respectively. Pathological analyses disclosed two major changes: glomerular alterations and endarteritis-like lesions of renal small arteries. The former included glomerular enlargement, cellular proliferation, mesangiolysis and marked swelling of endothelial-mesangial cells. This structural disorganization led to a reduction in renal function to some degree by impairing the glomerular circulation. Vasculopathy of the small artery probably resulted in progressive renal damage and ultimately to kidney contraction. Serum IL-6 was elevated in about 40% of cases. IL-6 levels were found to be high in the ascites of three patients who were examined. In different studies, an increased level of VEGF was found in the peripheral blood (75-100%; overall 92.3%), but no apparent correlation with glomerular alterations was observed. CONCLUSION: POEMS nephropathy can be one cause of end-stage renal disease with variable intrarenal pathological changes of a microangiopathic nature which have differential influences on renal function. A pathogenic role for VEGF in POEMS syndrome appears to be likely, but its causal relation to the nephropathy awaits further investigation.

Adult↗
PubMed1999

Distance-dose curve for a miniature x-ray tube for stereotactic radiosurgery using an optimized aperture with a parallel-plate ionization chamber.

A recently developed miniature x-ray tube operating at 40 kV has been used in a randomized trial for the treatment of small intracranial lesions. The diameter of these lesions ranges from 10 to 30 mm. A thin window parallel-plate ionization chamber was used to calibrate the output of the x-ray tube, modified by the addition of a thin platinum aperture to reduce the charge collecting area of the chamber. The effect of such an aperture on the measurement of dose versus distance from the x-ray tube in a phantom has been examined as a function of aperture diameter. Aperture diameters were varied between 0 and 5 mm and dose measurements were made for distances between the x-ray source and the front surface of the chamber of 5-30 mm in water. The ratio of doses measured with and without an aperture, when normalized to unity at a distance of 10 mm, differs significantly from unity, for distances between 7.5 and 15 mm, for aperture diameters <1.5 mm and differs from unity, but less significantly, for apertures > or =3 mm. For intermediate diameters, however, this dose dependence is minimized, indicating an aperture diameter that provides a similar distance-dose curve as the measurement taken without an aperture over this range of distances. This diameter was found to be between 2 and 2.5 mm with a dose variation of less than +/- 1%. For distances <7.5 mm, measurements made with a 1.5-mm-diam aperture agree better with those taken with a 1.7-mm-diam chamber compared with a 5.2-mm-diam chamber.

Dose-Response Relationship, Radiation↗
PubMed1999

Identification of a portable repression domain and an E1A-responsive activation domain in Pax4: a possible role of Pax4 as a transcriptional repressor in the pancreas.

Pax4 is a paired-domain (PD)-containing transcription factor which plays a crucial role in pancreatic beta/delta-cell development. In this study, we characterized the DNA-binding and transactivation properties of mouse Pax4. Repetitive rounds of PCR-based selection led to identification of the optimal DNA-binding sequences for the PD of Pax4. In agreement with the conservation of the optimal binding sequences among the Pax family transcription factors, Pax4 could bind to the potential binding sites for Pax6, another member of the Pax family also involved in endocrine pancreas development. The overexpression of Pax4 in HIT-T15 cells dose dependently inhibited the basal transcriptional activity as well as Pax6-induced activity. Detailed domain mapping analyses using GAL4-Pax4 chimeras revealed that the C-terminal region of Pax4 contains both activation and repression domains. The activation domain was active in the embryonic kidney-derived 293/293T cells and embryonal carcinoma-derived F9 cells, containing adenoviral E1A protein or E1A-like activity, respectively but was inactive or very weakly active in other cells including those of pancreatic beta- and alpha-cell origin. Indeed, the exogenous overexpression of type 13S E1A in heterologous cell types could convert the activation domain to an active one. On the other hand, the repression domain was active regardless of the cell type. When the repression domain was linked to the transactivation domain of a heterologous transcription factor, PDX-1, it could completely abolish the transactivation potential of PDX-1. These observations suggest a primary role of Pax4 as a transcriptional repressor whose function may involve the competitive inhibition of Pax6 function. The identification of the E1A-responsive transactivation domain, however, indicates that the function of Pax4 is subject to posttranslational regulation, providing further support for the complexity of mechanisms that regulate pancreas development.

Adenovirus E1A Proteins↗
PubMed1999

Pseudohypoparathyroidism type 1b in pregnancy.

Calcium-regulating hormones were serially measured during the second pregnancy in a woman with pseudohypoparathyroidism type 1b. Calcium levels corrected for serum albumin were maintained almost normal during her second pregnancy with 1alpha-hydroxycalciferol (2.0 microg daily) though they were slightly decreased in late pregnancy. 1,25-Dihydroxyvitamin D levels were higher in early and mid-pregnancy, but not in late pregnancy compared to those after delivery. Parathyroid hormone levels were higher in late pregnancy than after delivery.

Adult↗
PubMed1999

Effects of milk and colostrum on superoxide generation of oral polymorphonuclear neutrophils and the changes that occur during storage at low temperature.

Human oral polymorphonuclear neutrophils (OPMN) generate reactive oxygen species even in the absence of stimulants. Because OPMN from newborn babies are exposed to colostrum and mature milk, the biological properties of these cells including the generation of reactive oxygen species might possibly be affected by the constituents of colostrum and milk. The present work reports the effects of colostrum and mature milk, including the effects of storage at low temperature, on superoxide generation by OPMN. Fresh colostrum and mature milk did not affect either endogenous or formyl-methionyl-leucyl-phenylalanine-induced generation of superoxide by OPMN. However, superoxide generation stimulated by phorbol myristate acetate or arachidonic acid was inhibited by colostrum and mature milk presumably due to binding of the ligands to milk proteins. During the storage of milk at 4 degrees C, free forms of unsaturated long-chain fatty acids increased, and there was concomitant increase in the ability of milk to generate superoxide radicals in OPMN. Kinetic analysis suggested that colostrum and mature milk regulate superoxide generation by OPMN, thereby modulating the bactericidal activity of these cells in the oral cavity.

Animals↗
PubMed1999

Xenopus laevis pancreatic DNase I: purification and immunological characterization.

Deoxyribonuclease I (DNase I) was purified from Xenopus laevis pancreas to apparent electrophoretic homogeneity using a series of column chromatographies. The purified enzyme showed a molecular mass of about 36 kDa and maximum activity at pH 7.0-8.0, required divalent cations, Ca2+ and Mg2+, for its activity, and was inhibited by EDTA, EGTA and an antibody specific to the enzyme, but not by G-actin. The N-terminal amino acid sequence of the enzyme up to the 37th residue shared 38-44% homology with that of mammalian DNases I derived from bovine, ovine, porcine, rat, mouse, rabbit and human. A systematic survey of DNase I activity distribution in 20 different kinds of frog tissues showed that the pancreas and rectum produced higher amounts than other tissues. This is the first report concerning the purification and chemical and immunological characterization of frog pancreatic DNase I.

Amino Acid Sequence↗
PubMed1999

Serum levels of 20-kilodalton human growth hormone (GH) are parallel those of 22-kilodalton human GH in normal and short children.

Twenty-kilodalton human GH (20K), which is one of the human GH (hGH) variants, is thought to be produced by alternative premessenger ribonucleic acid splicing. However, its physiological role is still unclear due to the lack of a specific assay. We have measured serum 20K and 22-kDa hGH (22K) by specific ELISAs to investigate the physiological role of 20K in children. The subjects were 162 normal children, aged 1 month to 20 yr; 12 patients with GH deficiency (GHD), aged 11 months to 13 yr; 57 children with non-GHD short stature, aged 2-17 yr; and 13 girls with Turner's syndrome, aged 5 months to 15 yr. Samples were collected at random from normal children and were collected after hGH provocative tests and 3-h nocturnal sleep from GHD, non-GHD short stature, and Turner's syndrome children. The mean basal serum concentrations of 22K and 20K were 2.4 +/- 2.8 ng/mL and 152.3 +/- 184.0 pg/mL in normal boys and 2.5 +/- 3.1 ng/mL and 130.6 +/- 171.5 pg/mL in normal girls, respectively. The percentages of 20K (%20K) were 5.8 +/- 2.1% and 6.0 +/- 3.2% in 83 normal boys and 79 normal girls, respectively. There was no significant difference in %20K either among ages or between the prepubertal stage and the pubertal stage in normal boys and girls. The mean %20K values in basal samples of provocative tests in 12 patients with GHD, non-GHD short stature, and Turner's syndrome were 6.5 +/- 2.4%, 6.5 +/- 3.8%, and 5.9 +/- 3.2%, respectively. There was no significant difference in %20K among normal children and these growth disorders, and there was no significant difference in %20K throughout the hGH provocative tests and 3-h nocturnal sleep in these growth disorders. There was also no significant correlation between the percentage of 20K and the height SD score or body mass index in either normal children or subjects with these growth disorders. In conclusion, the %20K is constant, regardless of age, sex, puberty, height SD score, body mass index, and GH secretion status. The regulation of serum 20K levels remains to be established.

Adolescent↗
PubMed1999

Outcome of a baby born from a mother with acquired juvenile hypothyroidism having undetectable thyroid hormone concentrations.

We report a baby born from a mother with strongly positive thyroid stimulation blocking antibody (TSBAB) and nearly undetectable T4 level. This case is a unique model of nearly complete absence of thyroid hormones during fetal and early neonatal life in humans. The infant girl was born by cesarean section, because of fetal bradycardia, after 41 weeks gestation and received mechanical ventilation for 3 days. The TSH level was more than 120 microU/mL in the neonatal thyroid screening. At age 17 days, the results of a thyroid function study showed undetectable free T3 and free T4 concentrations, TSH 550 microU/mL, and TSH receptor antibody (TRAB) 87%. Thyroxine at a dose of 30 microg/day was started at age 17 days. The patient required thyroxine treatment until age 8 months. The brain magnetic resonance image at age 2 months revealed reduced brain size. Her auditory brain stem response was absent at age 2 months. The audiogram at age 4 yr revealed sensorineural deafness of 70 dB. When she was 6 yr of age, motor development remained the same as that at age 4 months. Her height was 106 cm (- 1.5 SD). The results of thyroid function study of the mother 23 days after delivery showed undetectable free T3 and free T4, TRAB 84%, and TSBAB 83%. In conclusion, the outcome of severe thyroid hormone deficiency in utero and early in human neonatal life was normal physical growth, fetal distress resulting in cesarean section, difficulty in the onset of breathing, permanent deficit in auditory function, brain atrophy, and severely impaired neuromotor development despite the start of an adequate dose of thyroxine replacement during the neonatal period.

Adult↗
PubMed1999

Geranylgeranylacetone induces apoptosis in HL-60 cells.

Geranylgeranylacetone (GGA) induces apoptosis in human leukemia HL-60 cells in a dose- and time-dependent manner. This effect was completely prevented by the pan-caspase inhibitor z-Val-Ala-Asp(OMe) fluoromethylketone, thereby implicating the caspase cascade in the process. Prior to DNA fragmentation, GGA treatment markedly activated caspase-3(-like) proteases, which might be responsible for the observed apoptosis. In addition, GGA treatment interfered with the processing and membrane localization of Rap1 and Ras, and these changes may be a result of apoptosis. Moreover, nitric oxide donors significantly accentuated the GGA-induced apoptosis, suggesting that the apoptotic pathway induced by GGA might be regulated by a redox-sensitive mechanism. Taken together, these data suggest that the isoprenoid, GGA, is an effective inducer of apoptotic cell death in HL-60 cells.

Amino Acid Chloromethyl Ketones↗
PubMed1999

The novel analgesic compound OT-7100 (5-n-butyl-7-(3,4,5-trimethoxybenzoylamino)pyrazolo[1,5-a]pyrimid ine) attenuates mechanical nociceptive responses in animal models of acute and peripheral neuropathic hyperalgesia.

We investigated the effects of OT-7100, a novel analgesic compound (5-n-butyl-7-(3,4,5-trimethoxybenzoylamino)pyrazolo[1,5-a]pyrimidi ne), on prostaglandin E2 biosynthesis in vitro, acute hyperalgesia induced by yeast and substance P in rats and hyperalgesia in rats with a chronic constriction injury to the sciatic nerve (Bennett model), which is a model for peripheral neuropathic pain. OT-7100 did not inhibit prostaglandin E2 biosynthesis at 10(-8)-10(-4) M. Single oral doses of 3 and 10 mg/kg OT-7100 were effective on the hyperalgesia induced by yeast. Single oral doses of 0.1, 0.3, 1 and 3 mg/kg OT-7100 were effective on the hyperalgesia induced by substance P in which indomethacin had no effect. Repeated oral administration of OT-7100 (10 and 30 mg/kg) was effective in normalizing the mechanical nociceptive threshold in the injured paw without affecting the nociceptive threshold in the uninjured paw in the Bennett model. Indomethacin had no effect in this model. While amitriptyline (10 and 30 mg/kg) and clonazepam (3 and 10 mg/kg) significantly normalized the nociceptive threshold in the injured paw, they also increased the nociceptive threshold in the uninjured paw. These results suggest that OT-7100 is a new type of analgesic with the effect of normalizing the nociceptive threshold in peripheral neuropathic hyperalgesia.

Amitriptyline↗
PubMed1999

Analysis of mfbA alleles of the eubasidiomycete Lentinus edodes.

A fruiting-body-specific mfbA cDNA derived from Lentinus edodes FMC2 has been shown to encode a high-molecular-weight protein, MFBA, containing the cell-adhesion-promoting Arg-Gly-Asp (RGD) sequence. Southern-blot analysis showed that all L. edodes strains tested have the mfbA gene (homologue). Nucleotide sequence analysis of the 1-kb mfbA fragments containing the RGD-coding sequence showed that each L. edodes strain has two types of mfbA homologues. It was found in FMC2 that two mfbA homologues are derived from different nuclei and these mfbA alleles are transcribed with similar frequencies in the fruiting bodies.

Alleles↗