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Biomedical subjects

T Saibara

Publications and source records attributed to T Saibara.

At least 37 records · Page 2Linked to original sources
PubMed1999

New approach to the medical information system for quality management in patient care: development of Problem Mapping System.

A new type of medical information system named Problem Mapping System (P-Map) has been developed, which aids physicians with solving patients' problems. With this system, physicians can define the problems of in-patients, monitor their progress clearly, and share information efficiently. In P-map, a list of problems, such as disease names, can be set for each inpatient easily. The progress of each problem is clearly shown using progress lines on a time axis. Physicians can save the Subjective Objective Assessment Plan (SOAP) notes which are linked to each problem. At the final stage of patient care, a discharge summary can be made easily. With the aid of this system, the quality of patient care is improved due to the following: (1) physicians can make the best decision; (2) medical staff in the same team can provide the best medical treatment; (3) evaluation of each medical treatment is easy; (4) saved data can be used effectively for education and research; (5) the system can improve cooperation with other medical institutes by providing discharge summary information which can be distributed using e-mail; and (6) the system can improve patients' understanding for the purpose of informed consent by providing clear and well organized information to patients.

Computer Systems↗
PubMed1999

Effects of Sho-saiko-to extract on liver fibrosis in relation to the changes in hydroxyproline and retinoid levels of the liver in rats.

To examine the effects of Sho-saiko-to extract on liver fibrosis, the drug was administered to rats with dimethylnitrosamine-induced liver-injury at various doses. Hydroxyproline and retinoid levels in the liver were measured as indicators of liver function. In liver-injured rats, the hydroxyproline level in the liver (957+/- 154nmol g(-1)) was about 4.16-times that found in normal liver (230+/-11 nmol g(-1)), but administration of Sho-saiko-to extract (0.75%, 1.5% or 3%) reduced the hydroxyproline level significantly (554+/-58, 356+/-51, 374+/-66nmol g(-1), P<0.01). Single administration of the active constituents of Sho-saiko-to extract, glycyrrhizin, baicalin or baicalein, decreased the hydroxyproline level significantly compared with the ordinary food group (P < 0.05), but the decrease was smaller compared with the Sho-saiko-to extract group. The liver retinoid level was higher in the Sho-saiko-to extract group than the ordinary food group and the value increased dose-dependently. A significant negative correlation, r=-0.814 (P<0.001) was detected between the hydroxyproline level and retinoid level in the liver of liver-injured rats. Significant negative correlations, r =-0.728 (P < 0.001) and r= -0.873 (P < 0.001), were also detected between the liver hydroxyproline level and the liver concentrations of the active constituents (glycyrretic acid, baicalin and baicalein) in the liver-injured rats. From these findings, it was considered that the liver concentrations of hydroxyproline and retinoid as well as the active constituents were involved in the improvement of liver fibrosis in the liver-injured rats administered Sho-saiko-to extract. Administration of Sho-saiko-to extract inhibited collagen production while an increase in retinoid level inhibited activation of Ito cells leading to inhibition and prevention of liver fibrosis.

Administration, Oral↗
PubMed1998

Transactivation of transforming growth factor alpha gene by hepatitis B virus preS1.

Hepatitis B virus (HBV) causes acute and chronic liver injury, and integration of HBV DNA is considered to be an important pathogenic determinant for hepatocarcinogenesis and tumor development. Transforming growth factor alpha (TGF-alpha) drastically accelerates hepatocarcinogenesis when it is overexpressed in TGF-alpha transgenic mice (C. Jhappan et al., Cell, 61: 1137-1146, 1990). In HBV-infected patients, hepatocellular carcinoma (HCC) cells show elevated expression of TGF-alpha (C. C. Hsia et al., J. Med. Virol., 43: 216-221, 1994), the mechanism for which, however, has not been clarified yet. We here show that preS1, a part of the HBV large surface protein, carries a transcriptional transactivation domain and activates the transcription of the TGF-alpha gene by 2-fold in human HCC HuH6 cells. The responsive elements are restricted to the 315-bp segment of the proximal TGF-alpha promoter (-373 to -59). Furthermore, the expression of TGF-alpha was markedly increased in permanently preS1-producing HuH6 transformants. The crucial role for HBV preS1 in hepatocarcinogenesis and tumor development through transactivation of the TGF-alpha gene may give us new insight into the understanding of pathogenesis and therapy of viral hepatocarcinogenesis.

Animals↗
PubMed1998

An enzymatic assay for erythrocyte creatine as an index of the erythrocyte life time.

OBJECTIVES: To establish and estimate an enzymatic measurement of creatine in erythrocytes as an index of the erythrocyte life time. DESIGN AND METHOD: The measurement of creatine in erythrocytes was performed using an enzymatic assay kit that was developed for serum and urine creatine. An erythrocyte sample was subjected to creatine measurement after hemolysis and deproteinization. Performance of the method for creatine measurement in erythrocytes was estimated. Effects of age and gender on the creatine content of erythrocytes were also estimated in 305 normal subjects. RESULTS: The method showed within-run CVs varying from 0.7 to 1.0% (n = 20), and between-day CVs from 1.3 to 1.7% (15 days). Good linearity was observed at least up to 1000 mumol/L as creatine value in hemolyzed sample. The analytical recovery was calculated to be 98.1 +/- 1.3% on average. No considerable interference by various substances, including guanidino compounds and amino acids, with the assay was observed. Excellent correlation was observed between the present method and high performance liquid chromatography. With the unit of mumol/g Hb: slope, 1.034 +/- 0.003 (mean +/- SD); intercept, -0.059 +/- 0.012 (mean +/- SD); correlation coefficient, 0.9996; and Sy.x, 0.069. With the unit of mumol/L RBC: slope, 1.033 +/- 0.003 (mean +/- SD); intercept, -18.23 +/- 3.55 (mean +/- SD); correlation coefficient 0.9996; and Sy.x, 20.40. A significant increase in erythrocyte creatine was observed in females aged 11- to 50 years old as compared with males in the corresponding age bracket, however, a gender difference was not observed in other age bracket. This finding suggests the possibility of a slight decrease in the erythrocyte life time due to menstruation in females. CONCLUSION: This study showed that the present method is favorable for quantifying erythrocyte creatine, and has analytical characteristics suitable for routine work in clinical laboratories.

Adolescent↗
PubMed1998

Novel physiological functions of cathepsins B and L on antigen processing and osteoclastic bone resorption.

Lysosomal cathepsin B plays an essential role in the processing of ovalbumin as an exogenous antigen to produce the complex between antigenic-peptide and major histocompatibility-complex class II. Administration of cathepsin B inhibitors, E-64, CA-074 and vitamin B6, caused the strong suppression of the Th-2 type immune responses. We found that pyridoxal phosphate (PAP), a coenzyme form of vitamin B6, inhibits the activities of cathepsin B and L in vitro and vitamin B6 administration induces the inhibition of the lysosomal cathepsin activities in vivo. The production of an antigenic epitope (I323-R339) of ovalbumin by antigen presenting cells was suppressed by cathepsin B specific inhibitors. The ovalbumin dependent production of immunoglobulins (IgE and IgG1) and of the corresponding interleukin (IL-4) was suppressed by cathepsin B inhibitors, while the production of IgG2a and interferon (INF-gamma) was increased. The switch of helper T lymphocyte functions from the type-2 to the type-1 may be induced by the cathepsin B inhibition. The experimental bone pit formation, i.e., osteoclastic bone collagen degradation test, induced by parathyroid hormone was markedly suppressed by the administration of pyridoxal, because of the inhibition of cathepsin L type cysteine proteases in bone.

Animals↗
PubMed1998

Characterization of cationic amino acid transporter and its gene expression in rat hepatic stellate cells in relation to nitric oxide production.

BACKGROUND/AIMS: Nitric oxide is a potent mediator of hepatic sinusoidal hemodynamics and affects hepatic stellate cells (Ito cells, fat-storing cells). Although nitric oxide production may depend on the induction of inducible nitric oxide synthase and on transport of extracellular L-arginine, the precise mechanisms controlling nitric oxide production in stellate cells have not been well characterized. METHODS: Using stellate cells prepared from the male Wistar rat, kinetic analysis of L-arginine transport and reverse transcription-polymerase chain reaction for cationic amino acid transporter were carried out. The effect of tumor necrosis factor-alpha and interferon-gamma on L-arginine transport, mRNA expression of cationic amino acid transporter and inducible nitric oxide synthase, and nitric oxide production of stellate cells was assessed. RESULTS: The L-arginine transport system functioning in the transformed hepatic stellate cells was system y+, possibly mediated by cationic amino acid transporter-1 and cationic amino acid transporter-2B (Km approximately 50 microM). Tumor necrosis factor-alpha enhanced cationic amino acid transporter-2B mRNA expression and L-arginine transport, whereas cationic amino acid transporter-1 mRNA expression remained unchanged. Interferon-gamma induced the expression of inducible nitric oxide synthase mRNA without obvious changes in L-arginine transport. Interferon-gamma in combination with tumor necrosis factor-alpha induced nitric oxide production with an enhancement in cationic amino acid transporter-2B mRNA expression, inducible nitric oxide synthase mRNA expression, and L-arginine transport, while extracellular L-lysine competitively inhibited this nitric oxide production. CONCLUSIONS: In transformed hepatic stellate cells, tumor necrosis factor-alpha and interferon-gamma have a crucial role in nitric oxide production, and extracellular L-arginine transport and inducible nitric oxide synthase expression are regulated in a differential cytokine-specific manner. As the estimated Km of L-arginine transporter in transformed hepatic stellate cells is very similar to the physiological L-arginine concentration in portal vein, we assume that increased portal L-arginine concentration may easily affect sinusoidal blood flow through enhancement of autocrine nitric oxide production in transformed hepatic stellate cells of diseased liver.

Amino Acid Transport Systems, Basic↗
PubMed1998

Abnormally decreased HbA1c can be assessed with erythrocyte creatine in patients with a shortened erythrocyte age.

OBJECTIVE: To investigate whether erythrocyte creatine can serve as a corrective index for HbA1c in patients with a shortened mean age of erythrocytes. RESEARCH DESIGN AND METHODS: HbA1c and creatine in density-fractionated erythrocytes from 18 normal subjects were measured. HbA1c and erythrocyte creatine in the whole blood of 43 patients with liver cirrhosis (LC), 14 patients with hemolytic anemia (HA), 38 other patients with high reticulocyte counts (HRC) (>2.2%), and 59 normal subjects were also measured. The patients in this study all had normal blood glucose levels. A correction formula derived from the linear regression equation for the correlation between HbA1c and erythrocyte creatine was used to correct the patients' HbA1c values. RESULTS: Among density-fractionated erythrocytes, the young cells exhibited low HbA1c and high creatine values. With progressively increasing density, HbA1c gradually increased and creatine gradually decreased. In the whole blood samples, the HbA1c values were significantly lower (P < 0.001) in LC, HA, and HRC patients than in normal subjects. By contrast, the erythrocyte creatine values were significantly higher (P < 0.001) in LC, HA, and HRC patients than in normal subjects. A linear correlation between HbA1c (y) and erythrocyte creatine (x) was observed (y=-0.224x + 5.00; n=154; r=-0.70; P < 0.001). Based on the regression equation, a correction formula was obtained. Low HbA1c values (<4.3%) were found in 24 of the 43 LC patients, 12 of the 14 HA patients, and 20 of the 38 HRC patients. After correction of the HbA1c values, 15 of the 24 LC patients, 9 of the 12 HA patients, and 16 of the 20 HRC patients had HbA1c values within the normal range. CONCLUSIONS: HbA1c decreased in inverse proportion to the increase in erythrocyte creatine because of a shortened mean age of erythrocytes. The abnormally decreased HbA1c value could be assessed with erythrocyte creatine.

Adult↗
PubMed1998

Sensitive enzymatic assay for erythrocyte creatine with production of methylene blue.

We developed a new, highly sensitive enzymatic method for quantifying creatine in erythrocytes, which comprises creatine amidinohydrolase, sarcosine oxidase, and peroxidase. In the present method, an N-methylcarbamoyl derivative of methylene blue, 10-N-methylcarbamoyl-3,7-bis(dimethylamino)phenothiazine (MCDP), was used as a sensitive chromogenic compound. Potassium ferrocyanide was used to prevent nonspecific oxidation of MCDP. The enzymatic method exhibited good analytical performance: precision, within-run CVs <1.0% and between-day CVs <2.0%; average analytical recovery, 99.3% +/- 1.8%; detection limit, 1.0 micromol/L in hemolysate; and linearity, at least up to 500 micromol/L as creatine concentration in hemolysate. Excellent agreement was observed between the present method (y) and HPLC (x), y = 1.029x - 0.002 micromol/g hemoglobin, r = 0.9998, S(y/x) = 0.053 micromol/g hemoglobin (n = 110). No significant interference was produced by various compounds, including guanidino compounds, amino acids, and reducing materials. The reference intervals (mean +/- 2 SD) for erythrocyte creatine obtained from 60 males and 60 females were (in micromol/g hemoglobin) 1.18 +/- 0.52 (0.66-1.70) for males and 1.35 +/- 0.49 (0.86-1.84) for females. Using this method, we documented changes in erythrocyte creatine in patients with various hemolytic conditions, including hemolytic anemia, liver cirrhosis, renal insufficiency, and chronic renal failure treated with hemodialysis with or without the administration of erythropoietin. We conclude that the use of MCDP allows sensitive measurement of erythrocyte creatine and that MCDP with potassium ferrocyanide can improve the sensitivity of assays that use peroxidase for detection of H2O2.

Adult↗
PubMed1998

[ACTH receptor, ACTH receptor anomaly, and familial glucocorticoid deficiency].

Familial glucocorticoid deficiency (FGD) is an autosomal recessive syndrome with hereditary adrenocortical unresponsiveness to ACTH. After the cloning of ACTH receptor or melanocortin-2 receptor (MC-2R) cDNA, several kinds of mutations in the receptor genes have been reported. However, the apparently normal ACTH receptor gene in some affected children suggests that the etiology of FGD is heterogeneous. In this short review, we describe the recent advances in the molecular biology of ACTH receptor genes, its post-receptor signal transduction in the adrenocortical cells, and the molecular genetics of the FGD and a related syndrome, Allgrove syndrome. We also discuss that this kind of work will help us to understand better about the molecular mechanism of the glucocorticoidogenesis in the human being.

Glucocorticoids↗
PubMed1997

Development of hepatic sinusoidal structure with special reference to the Ito cells.

To elucidate sinusoidal cell structure and function under normal conditions and their behavior in diseased settings, an understanding of their developmental aspects is needed. At day 10 of gestation in mice and rats or at 5 weeks of gestation in humans, the hepatic cords grow into the mesenchymal tissue of the septum transversum, and the primitive sinusoidlike structure is simultaneously observed between the liver cell cords. In the margin of the growing liver primordium, mesenchymal cells in the septum transversum are trapped in the subendothelial space. These subendothelial cells are at the early stages of organogenesis and become progenitors of the Ito cells. By days 12-14 of gestation in mice and rats or 8 weeks of gestation in humans, the basic structure of the sinusoids has developed. Embryonic hepatic sinusoids are usually lined by a continuous endothelium without basement membranes, and an incompletely fenestrated sinusoid appears at the middle gestational stage. In the late gestational stages, the Ito cells exhibit myofibroblastlike features in humans, mice, and rats. In association with this event, perisinusoidal reticular networks are gradually intensified. After birth until days 4-5 in mice and rats, the sinusoidal and perisinusoidal structures are almost completely formed, although slight morphological differences from those in adult livers still exist. What happens to sinusoidal endothelial cells and Ito cells in hepatic fibrosis-cirrhosis of the adult may be a deviated or uncontrolled occurrence of what goes on during the fetal period, i.e., a continuous nonfenestrated sinusoidal lining in the early embryonic stage and a myofibroblastlike transformation of Ito cells in late fetal life.

Animals↗
PubMed1997

A dimeric form of soluble recombinant sheep LFA-3(CD58) inhibits human T-cell proliferation by generating regulatory T cells.

We recently observed that the soluble recombinant from of sheep LFA-3, termed sLFA-3 is biologically active as determined by E-rosette inhibition and inhibition of human T-cell proliferation in response to the recall antigen. In the present study, we examined the immunosuppressive properties of a derivative of sLFA-3, a dimeric form of the first domain (D1) of sLFA-3, named sD1Hcys dimer which was made by oxidative binding of the two D1 molecules through disulfide bonds formed between the SH side chains of a cysteine which was added to the C-terminal of the D1 domain. By investigating the suppressive properties of the sD1Hcys dimer, we obtained evidence that antigen-stimulated T-cell proliferation was inhibited by the suppressor T cell, mainly CD4 + CD45RA - CD45RO + and CD8 + CD45RA - CD45RO + T cells, generated by incubating PBLs with a low dose (0.5 microgram/ml) of sD1Hcys dimer in the presence of a low dose of IL-2 and GM-CSF. Flow cytometric analysis showed that the expression of some surface molecules on T cells were modulated by a high dose (5 micrograms/ml) of sD1Hcys dimer such as downregulation of CD3 and upregulation of IL-2R, but were not modulated by a low dose (0.5 microgram/ml) of the sD1Hcys dimer. These findings suggest that the sD1Hcys dimer exerts its suppressive effects on the antigen-induced proliferation assay by generating suppressor T cells. The sD1Hcys dimer might therefore have potential as an immunotherapeutic agent to inhibit and/or anergize antigen-specific T-cell responses.

Animals↗
PubMed1996

Substitutions in the HLA-DR alpha chain differentially affect DR7-restricted T-cell recognition of rabies virus antigen.

To investigate the functional roles of DR alpha residues in T-cell recognition, 20 mutants of the DR alpha chain were constructed by site-directed mutagenesis. These DR alpha mutants were expressed with WT DR(beta 1*0701) on mouse L cells and used as APC for four DR7-restricted T-cell clones specific for rabies virus antigens. The results indicate that the DR alpha residues are differentially involved in recognition of rabies virus antigen by different T-cell clones. Mutations in the floor of the antigen-binding groove (positions 9, 11, 22, and 24), on the alpha-helix (47, 55, 65, 66, and 72), and surprisingly on the outer loop (15, 18, and 19), abrogated recognition by at least one T-cell clone. Most of these residues appear to be involved in either peptide or TCR contact, based on the DR1 crystal structure. The involvement in T-cell recognition of DR alpha residues located in the outer loop outside the binding groove suggests that these residues may directly contact TCR, or indirectly contribute to the conformation of peptide sitting in the groove.

Amino Acid Sequence↗
PubMed1995

Sequential changes in human Ito cells and their relation to postnecrotic liver fibrosis in massive and submassive hepatic necrosis.

To examine the relationship of Ito cells to postnecrotic liver fibrosis, liver specimens, obtained at autopsy from 17 patients with acute massive necrosis (AMN) and acute submassive hepatic necrosis (ASMN), were examined immunohistochemically. In normal adult livers, Ito cells positive for alpha-smooth muscle actin isoform (ASMA) were rarely seen, scattered along hepatic sinusoids. In contrast, in AMN the Ito cells in necrotic areas became strongly positive for ASMA. They were swollen with elongated cytoplasmic processes along collapsed sinusoidal walls. Around these ASMA-positive Ito cells, there were numerous infiltrated macrophages and lymphocytes present. There was no significant alteration of fibroblasts in the portal tracts. In the middle and late stages of ASMN, the spindle-shaped ASMA-positive Ito cells formed a continuous cellular network. New fibre formation was predominantly around them. In this immediate postnecrotic fibrosis, ASMA-positive stromal cells of Ito cell origin were distributed irregularly and were closely associated with reticulin and newly-formed collagen fibres. Regenerative nodules were surrounded by dense layers of ASMA-positive stromal cells. Throughout the stages of ASMN, portal fibroblasts remained negative for ASMA. We believe that Ito cells in necrotic areas show myofibroblastic transformation and play a central role in the postnecrotic liver fibrosis. Portal fibroblasts play no significant part in this type of fibrosis.

Actins↗