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Biomedical subjects

T Ono

Publications and source records attributed to T Ono.

At least 307 records · Page 17Linked to original sources
PubMed1999

Rapid normalization of interleukin-8 production after low-density lipoprotein apheresis in steroid-resistant nephrotic syndrome.

BACKGROUND: Low-density lipoprotein apheresis (LDL-A) treatment combined with steroids demonstrated significant improvement of nephrotic proteinuria in steroid- or immunosuppressive-resistant patients from focal and segmental glomerulosclerosis (FGS). The mechanisms of the effect of LDL-A in nephrotic syndrome (NS) are unknown, but a reduction in inflammatory cytokines and chemokines secreted from macrophages has been supposed. METHODS: Serum levels of interleukin (IL)-8, tumor necrosis factor-alpha (TNF-alpha), and monocyte chemoattractant protein-1 (MCP-1) were measured by enzyme-linked immunosorbent assay in 27 patients with NS [13 with FGS and 14 with minimal change nephrotic syndrome (MCNS)] before and after LDL-A and in 13 age-matched, healthy controls. We also selected three FGS patients who were resistant to steroid therapy for at least one month and who had undergone six LDL-A procedures. The effects of steroids and LDL-A on the production of IL-8, TNF-alpha, and MCP-1 by peripheral blood mononuclear cells (PBMCs) were also determined in some patients. RESULTS: In NS, the serum levels of IL-8 and TNF-alpha, but not MCP-1, were significantly higher than in healthy controls. After LDL-A, IL-8 and TNF-alpha tended to decrease. IL-8 production by lipopolysaccharide (LPS)-stimulated PBMC, mainly adherent cells, was significantly reduced in both the steroid-resistant FGS group and nontreated NS group compared with controls, but TNF-alpha production was reduced in the only FGS group. After LDL-A, only IL-8 production recovered to the control group level. CONCLUSION: Significant amelioration of IL-8 production independent of any effect of steroids on LPS-stimulated PBMCs may reflect a beneficial effect of LDL-A in normalizing the function of circulating monocytes in steroid-resistant FGS.

Blood Component Removal↗
PubMed1999

Effect of a new inhibitor of type II phospholipase A2 on experimental acute pancreatitis in rats.

The catalytic activity of type II phospholipase A2 (PLA2) in blood has been reported to increase in acute pancreatitis and to reflect the severity of pancreatitis. In this study, we evaluated the effects of a new inhibitor of type II PLA2, S5920/LY315920Na, on trypsin-taurocholate-induced pancreatitis in rats. Hemorrhagic pancreatitis was induced by an infusion of a mixture of trypsin and taurocholate into the pancreatic duct. S5920/LY315920Na was administered subcutaneously at 0 h and 3 h after the induction of pancreatitis. Survival rates for 24 h in rats treated with 0.1 and 1 mg/kg of S5920/LY315920Na were significantly higher than that in untreated rats (71 and 86% vs. 14%). Serum levels of amylase and lipase in rats treated with 1 mg/kg of S5920/LY315920Na were significantly lower than those in untreated rats (amylase, 6,903 vs. 32,516 U/L; and lipase, 514 vs. 6,710 U/L) at the time of death or 24 h after the induction of pancreatitis. Plasma levels of S5920/LY315920Na were enough to inhibit catalytic activity of PLA2 in plasma for 9 h. A new inhibitor of type II PLA2, S5920/LY315920Na, inhibited catalytic activity of PLA2 and improved the survival rate in experimental hemorrhagic pancreatitis in rats.

Acetates↗
PubMed1999

UVB-induced gpt mutations in the skin of gpt delta transgenic mice.

Ultraviolet light B (UVB)-induced mutagenesis was studied in gpt delta transgenic mice, which contain the lambdaEG10 shuttle vector as a transgene. The mice were exposed to UVB at single doses of 0.3, 0.5, 1.0, 1.5, and 2.0 kJ/m(2). At 4 weeks after irradiation, the mutant frequencies (MF) of the gpt gene were determined in the epidermis and the dermis, and the gpt mutations in the epidermis were identified by DNA sequencing. The epidermis exhibited a higher sensitivity to UVB than the dermis at doses of 0.3 and 0.5 kJ/m(2) UVB: the MF of the epidermis were more than nine times higher than those of the nonirradiated mice, whereas the MF of the dermis were only two to three times higher than the nonirradiated level at the doses used. The UVB-induced mutation spectrum in the epidermis was dominated by G:C to A:T transitions at dipyrimidine sites, such as 5'-TC-3', 5'-CC-3', and 5'-T/C-CG-3'. Tandem transitions such as CC to TT were also observed. Interestingly, a remarkable bias towards the template strand of the gpt gene was observed in the single transitions at 5'-TC-3' and 5'-CC-3' sites, but not at 5'-T/C-CG-3' site. In contrast, G:C to A:T transitions at CpG sites and deletions were observed in nonirradiated mice. Hot spots of transitions were observed at different sites in UVB-irradiated and nonirradiated mice. These results indicate that gpt delta transgenic mouse is a suitable model for studying in vivo UVB-induced mutations at the molecular level.

Animals↗
PubMed1999

Molecular nature of mutations induced by a high dose of x-rays in spleen, liver, and brain of the lacZ-transgenic mouse.

DNA sequences of 103 spontaneous mutants and 102 X-ray-induced mutants of the lacZ transgene from spleen, liver, and brain of the MutaMouse were examined and compared to elucidate characteristics of radiation-induced mutations in vivo. The radiation-induced mutants were isolated from genomic DNA of each tissue collected at 3.5 days after 200 Gy of whole body irradiation. Base substitution was predominant (80% or more) in nonirradiated tissues, while deletion was prevalent (about 55%) in irradiated tissues. The other types of mutation appeared at similar frequencies in both control and irradiated tissues. The size of the deletions was smaller than 438 nucleotides, with a predominance of one basepair deletions in both control and irradiated tissues. A close look at the nucleotides at the deletion endpoints revealed that many of the radiation-induced deletions did not have repeated sequences at the break point termini, whereas all deletions found in unirradiated tissues showed one or more bases of repeated sequences at the termini. Further, eight complex-type deletion mutations were found only in irradiated tissues. Comparison among the three types irradiated tissue did not reveal any tissue-specificity. The data indicate that the molecular nature of mutations induced in tissues with ionizing radiation is different from that of spontaneous mutations.

Animals↗
PubMed1999

[Ultrasound-guided fine-needle aspiration cytology for neck lesions].

In 1997, 240 cases of ultrasound-guided fine-needle aspiration cytology (FNAC) were performed for neck lesion at Jichi Medical School Hospital. We compared the preoperative cytology findings with postoperative pathologic results for 63 cases (56 lesions) from patients who underwent surgery or open biopsy. The sensitivity, specificity and accuracy of cytological diagnosis were 93.5%, 100% and 96.2%, respectively. There were 2 false negative cases in thyroid gland, which were follicular and medullary carcinomas. Insufficient material for cytological analysis was obtained in 62 of 240 cases (25.8%). Since FNAC can provide high accuracy, we need to reduce insufficient material cases.

Biopsy, Needle↗
PubMed1999

[A case of significant natriuresis and improvement of proteinuria by Temocapril, an ACE inhibitor with biliary excretion, in loop diuretics resistant edema in membranous nephropathy].

A 50-year-old man with WPW syndrome and chronic atrial fibrillation controlled by digoxin exhibited nephrotic syndrome due to membranous nephropathy in 1994. For massive edema resistant to loop diuretics, administration of 2 mg/day of Temocapril, an ACE inhibitor with biliary excretion, was started. It provided marked natriuresis and rapid improvement of massive anasarca. Moreover, 6 months later at the time of writing this report, nephrotic proteinuria has decreased and abnormally depressed Ccr level has elevated. For massive edema resistant to loop diuretics in nephrotic syndrome, Temocapril might bring about a beneficial effect possibly through the induction of natriuresis, which has been suppressed by the over-expression of angiotensin II in tubulointerstitium.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1999

[Lidocaine metabolism associated with epidural anesthesia in patients for hepatic surgery].

We measured plasma concentrations of lidocaine and its principal metabolite, monoethylglycinexylidide (MEGX) associated with thoracic epidural anesthesia using continuous infusion of lidocaine in 10 patients for hepatectomy and other 10 patients for elective abdominal surgery as a control. Plasma concentrations of lidocaine and MEGX were analysed by fluorescence polarization immunoassay and high performance liquid chromatography, respectively. Plasma lidocaine concentration increased gradually, and peaked to 5.1 +/- 2.3 micrograms.ml-1 (mean +/- SD) at the end of surgery in the hepatectomy group, but not in the control group. No significant differences were observed in plasma MEGX concentration between these two groups. Our findings suggest that MEGX formation by the hepatic cytochrome P-450 system might be impaired associated with hepatic surgery. Hypoperfusion of the liver induced by surgical manipulation may have contributed to this impaired metabolism.

Aged↗
PubMed1999

History of the Vessel Corkstopper for liquid medicines in Japan.

In this report it was found that in 1860, namely Gan-nen of Man-en in Japanese, cork caps were used for bottles of liver oil produced at fukuoka-han. On the other hand, it was previously proposed that the cork cap was first used for bottles of eye medicine, "Seikisui." This use occurred at least after 1867, namely the Third year of Keiou in Japanese. Therefore, it was clarified that the cork cap was used for liquid medicine in the form of a stopper for bottles of liver oil at least several years earlier than for "Seikisui."

Drug Packaging↗
PubMed1998

Effects of D2 dopamine receptor agonist and antagonist on brain activity in the rat assessed by functional magnetic resonance imaging.

The effects of D2 dopamine receptor agonist, bromocriptine (BROMO), and antagonist, haloperidol (HPD), on brain activity were investigated in rats by functional magnetic resonance imaging. T2*-weighted signal intensity was increased in the hypothalamus at 120 min after acute administration of BROMO, and in the ventral posterior and dorsomedial nuclei of the thalamus from 30 to 120 min. In contrast, the signal intensity was decreased in the caudate-putamen at 30 min after acute administration of HPD, in the hypothalamus from 30 to 60 min, and in the perirhinal cortex at 30 min. After chronic (2 weeks) HPD treatment, acute administration of HPD decreased signal intensity in the caudate-putamen at 60 min, in the hypothalamus at 30 min, the perirhinal cortex from 2 to 120 min, the dorsomedial and ventral posterior nuclei of the thalamus from 2 to 120 min, and the medial nucleus of the amygdala from 60 to 120 min. These results suggest that (1) the D2 receptor agonist increased the activity of the thalamic nuclei and the hypothalamus, while the D2 receptor antagonist suppressed brain activity in the regions where D2 receptors were present, (2) the suppression of brain activity in the thalamic nuclei and the perirhinal cortex by acute HPD administration was enhanced by chronic HPD treatment, and (3) the effects of antipsychotic drugs on the thalamus, amygdala, and perirhinal cortex may be related to their therapeutic efficacy, since clinical improvement in schizophrenic patients appears several days after the start of HPD treatment.

Amygdala↗
PubMed1998

Hypothalamic control of amino acid appetite.

Preference for umami taste materials, such as monosodium L-glutamate (MSG) and the 5'-ribonucleotides, inosine 5'-monophosphate (IMP) and guanosine 5'-monophosphate (GMP), varies as a consequence of protein nutrition. Rats fed diets deficient in dietary protein or an essential L-amino acid (AA), L-lysine (Lys), avidly consumed Lys, glycine and NaCl but not umami substances. However, when the rats' protein nutrition was normal or when they were recovering from deficiency, a preference for umami substances was evident. These data suggest that the central mechanism for recognition of protein malnutrition may be coupled with umami taste preference. To test this, Lys-deficient and normal rats were employed as a model for taste preference changes. AA levels in plasma and brain remain essentially unchanged throughout the day while the rat is on standard chow but are altered during Lys deficiency. The recognition site for the deficit in the rats' brains was localized to the ventromedial (VMH) and lateral (LHA) hypothalamus as determined by functional magnetic resonance imaging (fMRI, 4.7 Telsa). Studies of single neuron activity in the LHA of Lys-deficient rats suggested that neuronal plasticity occurred. Following Lys deficiency, cells responded specifically to Lys, both iontophoretically applied and during ingestion of AA. Other LHA neurons of nondeficient rats differentially responded to MSG. The present results suggest that the LHA and probably the VMH play important roles in recognition of deficient nutrients. Neural plasticity of hypothalamic cells helps maintain AA homeostasis. Furthermore, a preference for umami substances may be an indicator that the organism (rat or human) is free of protein malnutrition.

Amino Acids↗
PubMed1998

A phosphatidylinositol 3-kinase inhibitor wortmannin induces radioresistant DNA synthesis and sensitizes cells to bleomycin and ionizing radiation.

ATM and DNA-dependent protein kinase catalytic subunit (DNA-PKcs) have been shown to have sequences homologous to the catalytic domains of mammalian phosphatidylinositol 3-kinase (PI3-kinase). In order to determine the contribution of ATM and DNA-PKcs to the increased sensitivity of cells to DNA-damaging agents observed in the presence of PI3-kinase inhibitors, we examined the effects of a PI3-kinase inhibitor, wortmannin, on cellular sensitivity to bleomycin (BLM), mitomycin C (MMC), X-irradiation and ultraviolet (UV)-irradiation using 2 human tumor cell lines (T98G and A172), a human fibroblast cell line (LM217), an ataxia telangiectasia (AT) cell line (AT3BISV), a scid murine cell line (SCF) and a control murine cell line (CBF). Wortmannin sensitized all of the cells, including AT3BISV and SCF, to BLM and X-irradiation, but not to MMC or UV-irradiation. Hypersensitivity to BLM and X-irradiation and normal sensitivity to MMC and UV-irradiation are characteristic phenotypes of both AT and scid mice. DNA-dependent protein kinase (DNA-PK) activity was suppressed by wortmannin to 45-65% of the control values in all of the cells except SCF, in which DNA-PK activity was not detected. Wortmannin also induced radioresistant DNA synthesis, which is a cellular phenotype of AT, in T98G and SCF cells, but did not change the DNA synthesis rates after X-irradiation in AT3BISV. Our data suggest that wortmannin decreases the activities of both the ATM protein and DNA-PK, indicating that it might be of use as a sensitizing agent for radiotherapy and chemotherapy.

Androstadienes↗
PubMed1998

Alterations in TCR-MHC contacts subsequent to cross-recognition of class I MHC and singly substituted peptide variants.

Vesicular stomatitis virus (VSV) elicits H-2Kb-restricted CTLs specific for the immunodominant VSV octapeptide RGYVYQGL. To study the structural features important for interaction between the TCR beta-chain and the peptide/MHC complex, we immunized TCR alpha-chain transgenic mice with the VSV peptide and raised a panel of anti-VSV CTL clones with identical TCR alpha-chains. Consistent with our previous analysis of uncloned populations of primary CTLs, the anti-VSV CTL clones were all Vbeta13+ and expressed TCR beta-chains with highly homologous complementarity-determining region 3 (CDR3) loops. Although the clones expressed similar TCRs, they differed in their ability to cross-react with VSV peptide variants singly substituted at TCR contact positions 4 and 6. These findings allowed us to identify short stretches of amino acids in the C-terminal region of the CDR3beta loop that, when altered, modify the cross-reaction capability of the TCR to position 4 and position 6 variant peptides. To further probe the structural correlates of biologic cross-reactivity, we used cross-reactive CTL clones and cell lines expressing point mutations in H-2Kb to investigate the effect of single amino acid changes in the peptide on the pattern of recognition of the TCR for the peptide/MHC complex. Single conservative substitutions in the peptide were sufficient to alter the recognition contacts between a cross-reactive TCR and the MHC molecule, supporting the idea that the TCR can make overall structural adjustments in MHC contacts to accommodate single amino acid changes in the peptide.

Amino Acid Substitution↗
PubMed1998

Activity-dependent survival and enhanced turnover of calcium in cultured rat cerebellar granule neurons.

Neurons survive when their activity is maintained. An influential hypothesis on the cellular mechanism underlying this phenomenon is that there is an appropriate range of intracellular Ca2+ concentration ([Ca2+]i) for survival. The rat cerebellar granule neuron in culture serves as the most often used model system for the analysis of activity-dependent survival, since it does not survive unless an excitant (KCl or glutamate) is added to the culture medium. Against the above-mentioned hypothesis, we found in our previous examination no difference between steady-state [Ca2+]i in granule neurons cultured under high KCl (i.e., survival) and low KCl (i.e., death) conditions. In this report, we present the quantitative background of unchanged [Ca2+]i between the two culture conditions. Influx of Ca2+ due predominantly to L-type voltage-dependent calcium channels was higher in high KCl cultures than in low KCl cultures. At the same time, efflux of Ca2+ due to the activity of Ca2+/Na+ antiport was also higher in high KCl cultures. Additionally, we found that the endocytotic activity was greater in high KCl cultures than in low KCl cultures, as monitored by the rate of uptake of horseradish peroxidase added to medium. Since the uptake was blocked by an internal Ca2+ chelator, the increased endocytotic activity in high KCl cultures might be a consequence of the enhanced Ca2+ turnover.

Animals↗
PubMed1998

Major histocompatibility complex class I-restricted T cells are required for all but the end stages of diabetes development in nonobese diabetic mice and use a prevalent T cell receptor alpha chain gene rearrangement.

Nonobese diabetic (NOD) mice develop insulin-dependent diabetes mellitus due to autoimmune T lymphocyte-mediated destruction of pancreatic beta cells. Although both major histocompatibility complex class I-restricted CD8(+) and class II-restricted CD4(+) T cell subsets are required, the specific role each subset plays in the pathogenic process is still unclear. Here we show that class I-dependent T cells are required for all but the terminal stages of autoimmune diabetes development. To characterize the diabetogenic CD8(+) T cells responsible, we isolated and propagated in vitro CD8(+) T cells from the earliest insulitic lesions of NOD mice. They were cytotoxic to NOD islet cells, restricted to H-2Kd, and showed a diverse T cell receptor beta chain repertoire. In contrast, their alpha chain repertoire was more restricted, with a recurrent amino acid sequence motif in the complementarity-determining region 3 loop and a prevalence of Valpha17 family members frequently joined to the Jalpha42 gene segment. These results suggest that a number of the CD8(+) T cells participating in the initial phase of autoimmune beta cell destruction recognize a common structural component of Kd/peptide complexes on pancreatic beta cells, possibly a single peptide.

Amino Acid Sequence↗
PubMed1998

Abnormality of alpha-adrenergic vascular response in patients with neurally mediated syncope.

Although diagnosis of neurally mediated syncope (NMS) using the head-up tilt (HUT) test has been established, the precise etiologic mechanism of NMS is still obscure. Previously, we reported the contribution of impaired alpha-adrenergic vascular response to syncope in patients with various arrhythmias. This study evaluates alpha-adrenergic vascular response in 21 NMS patients with syncope and a positive HUT test (80 degrees, 30 minutes, and low-dose isoproterenol, NMS group, mean age 31 +/- 14 years) and 21 control subjects (C group, 33 +/- 14 years) who had no evidence of syncope and no structural heart disease. After 30 minutes in a recumbent position, pharmacologic total autonomic blockade was attained using atropine and propranolol. Thereafter, increased systolic blood pressure with 0.4 microg/kg/min phenylephrine (designated as deltaBPphenyl) and decreased systolic blood pressure with 0.5 microg/kg/30 seconds of phentolamine (designated as deltaBPphent) were measured as indexes of alpha-adrenergic vascular sensitivity and activity, respectively. DeltaBPphenyl in the NMS group (70.0 +/- 37) was significantly less than that in C group (107 +/- 38, p <0.005). DeltaBPphent was significantly greater in the NMS group than in the C group (33.5 +/- 10 vs 21.0 +/- 14, p <0.005). Thus, decreased alpha-adrenergic vascular sensitivity and elevated alpha-adrenergic vascular tone were observed in patients with NMS. Although it is not known whether the mechanism causing NMS can be attributed to this abnormal alpha-adrenergic vascular response, the abnormality could at least contribute to augmenting the symptoms of NMS.

Adrenergic alpha-Agonists↗
PubMed1998

Identification of the catalytic triad of the protein D2 protease in Pseudomonas aeruginosa.

We reported recently that protein D2 (OprD) porin of Pseudomonas aeruginosa bears protease activity (FEBS Letters 394, 179-182, 1996). To identify the catalytic residues of OprD, we introduced the site-directed mutations replacing the putative catalytic triad His156, Asp208, and Ser296 with glutamine, asparagine, and alanine, respectively. The OprD proteins purified from the chromosomal oprD-deficient mutants harboring the plasmids encoding the site-directed mutations showed protease activity less than 0.1% of that of the wild-type OprD. These site-directed mutageneses caused undetectable changes in the pore-forming activity of OprD as measured by single-channel conductance by the planar lipid bilayer. The minimum inhibitory concentration of imipenem in mutants having the replaced catalytic triads was identical with that in the wild-type strain. On the other hand, introduction of the mutation at His367 replacing with glutamine, the site that is supposed to be unrelated to the catalytic sites, showed the unchanged protease activity. These results unequivocally demonstrate that OprD is the protease bearing porin and catalyzes the reaction at His156, Asp208, and Ser296 residues.

Alanine↗
PubMed1998

MALDI-TOF mass spectrometric typing of single nucleotide polymorphisms with mass-tagged ddNTPs.

A matrix-assisted laser desorption/ionization time-of-flight mass spectrometry based method has recently been reported for the typing of single nucleotide polymorphisms using single nucleotide primer extension. This method is limited in some cases by the resolution of the mass determination, as the mass difference between nucleotides can be as little as 9 Da (the difference between A and T). A variation of this method is described here in which a mass-tagged dideoxynucleotide is employed in the primer extension reactions in place of the unmodified dideoxynucleotide. The increased mass difference due to the presence of the mass-tags substantially improves the accuracy and versatility of the procedure.

Dideoxynucleosides↗