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Biomedical subjects

H Sugimoto

Publications and source records attributed to H Sugimoto.

At least 19 recordsLinked to original sources
PubMed1997

Crystallization and preliminary X-ray analysis of human D-dopachrome tautomerase.

D-Dopachrome tautomerase catalyzes the conversion of D-dopachrome to 5,6-dihydroxyindole. This protein has amino acid sequence homology with that of macrophage migration inhibitory factor (MIF), suggesting a pathophysiological role of this protein in inflammatory and immunological events. We previously determined the tertiary structure of MIF and revealed the functional and evolutional relationships of this protein to isomerase. However, the reaction mechanism of both proteins associated with the inflammatory response, immune system, or tautomerase activities in vitro have not yet been clarified. The tertiary structure of D-dopachrome tautomerase would provide insight into the molecular function and the mechanism of these proteins. In this study, we crystallized human D-dopachrome tautomerase by a hanging-drop vapor diffusion method. The crystals belong to the trigonal space group P3, with unit cell dimensions a = b = 84.2 A and c = 41.0 A. They contain three (or two) monomers in the asymmetric unit, corresponding to a VM value of 2.21 (or 3.32) A3 Da-1. The best crystals diffract X-ray to 1.6 A resolution using a synchrotron radiation source. Crystallization of the selenomethionyl derivative of the protein for applying the multiwavelength anomalous diffraction method was also successful.

Chromatography, Gel↗
PubMed1997

Paradoxical positive nitrogen balance in burn patients receiving high-dose administration of insulin for nutritional care.

BACKGROUND: Nitrogen balance in patients who need high-dose administration of insulin has not been evaluated clinically. The purpose of this study was to compare the difference in nitrogen balance between burn patients who received high-dose administration of insulin and those who did not. METHODS: This study was performed in 19 severely burned adults with no liver or kidney failure. Patients were divided into two groups on the basis of the mean ratio of administered insulin and calorie intake (I/C) for the initial 4 weeks, a high I/C group (n = 9) and a low I/C group (n = 10). There were no significant differences between the two groups regarding age, percentage of area burned, and body weight. Nitrogen balance, blood urea nitrogen, and urine urea nitrogen were measured in all patients. Plasma concentrations of glucose, insulin, glucagon, cortisol, and urinary excretion of 3-methyl-histidine were measured in 12 patients (six in each group). RESULTS: Until day 10 both groups exhibited similar changes in plasma concentrations of glucose, insulin, glucagon, and cortisol. Subsequently, plasma concentrations of insulin and glucagon began to decrease in the low I/C group, whereas a high level was sustained in the high I/C group (p < 0.05). Plasma glucose and cortisol measurements showed no significant differences between the two groups. Blood urea nitrogen levels and urinary excretion of 3-methyl-histidine were not different between the two groups. Urine urea nitrogen excretion in the high I/C group, however, was significantly lower than that in the low I/C group from day 8 (p < 0.05). Thus the high I/C group achieved positive nitrogen balance more quickly than the low I/C group. Paradoxically, however, the high I/C group was at higher risk of septic complications and exhibited higher mortality than the low I/C group (p < 0.05). CONCLUSIONS: These results indicate that an improvement in nitrogen balance, which is accepted as a good thing in the management of critically ill patients, is not necessarily good in the high I/C group and that residual nitrogen was retained within the body in the high I/C group.

Adult↗
PubMed1997

Effects of eicosanoids on lipopolysaccharide-induced ornithine decarboxylase activity and polyamine metabolism in the mouse liver.

BACKGROUND/AIMS: During endotoxic shock, arachidonic acid is released from the inflammatory cell membranes and is metabolized to form eicosanoids, which modify the deleterious effects of lipopolysaccharide (LPS) on liver function. However, it is not known which prostaglandins (PGs) or leukotrienes (LTs) are produced or how they affect the LPS-treated liver. As LPS treatment elevates hepatic ornithine decarboxylase (ODC) activity and affects the polyamine levels of the mouse liver, this study was carried out to examine the effects of eicosanoids and their inhibitors on the induction of ODC activity and polyamine levels in the LPS-treated mouse liver. METHODS: LPS in the presence or absence of other drugs was intraperitoneally administered to 6-week-old mice and the livers were then removed. The hepatic ODC activity, polyamine levels, and level of ODC mRNA were determined. RESULTS: The levels of LPS-induced ODC activity, the putrescine (PUT) and N1-acetylspermidine (A-SPD) were reduced by the administration of PGE1. ODC activity was enhanced by the administration of corticosterone, AA-2414 (an antagonist of thromboxane (TX) A2) and TXB2, whereas the A-SPD level was reduced by corticosterone and AA-2414 treatment. The level of ODC mRNA changed in parallel with the change in ODC activity. CONCLUSIONS: PGE1 may reduce the LPS-induced production of inflammation-accelerating cytokines and reduce the level of ODC activation. Corticosterone and AA-2414 treatment may attenuate the LPS-induced production of eicosanoids, and enhance the LPS-induced ODC activation. It is possible that the eicosanoids produced by LPS treatment inhibit ODC activation during endotoxic shock.

Alprostadil↗
PubMed1997

Antithyroid therapy improves bony manifestations and bone metabolic markers in patients with Graves' thyrotoxicosis.

OBJECTIVE: Abnormal bone metabolism in patients with Graves' thyrotoxicosis is well documented, but the precise time-course of its recovery remains poorly understood. The present study was undertaken to clarify longitudinal improvement in bony manifestations, especially in cortical bone, and bone metabolic markers in thyrotoxicosis. DESIGN: Two year prospective follow-up study in patients with Graves' disease. PATIENTS: Ten consecutive patients with Graves' disease (seven males and three females, of mean (+/-SEM) age 39.3 +/- 3.9 years) were enrolled in the study and treated with antithyroid drugs. Thirteen sex- and age-matched patients with the disease in remission served as controls. MEASUREMENTS: Bony manifestations were evaluated both by fine cortical bone striations in the metacarpals on magnified roentgenograms and lumbar bone mineral density (BMD) measurement. Urinary deoxypyridinoline (dPYR) and serum pyridinoline cross-linked telopeptide domain of type I collagen (ICTP) were monitored as markers of bone resorption, as well as serum osteocalcin (OC), carboxy-terminal propeptide of type I procollagen (PICP) and alkaline-phosphatase (ALP) as markers of bone formation. RESULTS: Initial elevated free thyroid hormone levels were normalized within a month of starting therapy. Striation indices of the metacarpals were 1.89 +/- 0.16 before therapy, higher than those of 0.49 +/- 0.12 in the controls (P < 0.0001); the indices gradually decreased to 1.00 +/- 0.20 (12 months) and 0.48 +/- 0.12 (24 months). Lumbar BMD Z-scores increased from -0.22 +/- 0.46 to 0.21 +/- 0.47 (12 months) and 0.68 +/- 0.48 (24 months) (P = 0.0029). Before therapy, urinary dPYR and serum ICTP concentrations were much higher than the control values (dPYR, +553%; ICTP, -396%, P < 0.0001), which declined promptly in the 2nd month. Serum OC, PICP and ALP were also significantly higher than in controls at first (OC, +287%; PICP, +225%; ALP, +196%), and remained elevated until 4 or 8 months. CONCLUSIONS: Bone resorption and cortical bone striations occur in untreated patients with Graves' thyrotoxicosis. The bone resorption rapidly ameliorates after normalization of thyroid hormone levels. In contrast, the accelerated bone formation persists for at least 4-8 months, suggesting positive uncoupling of bone remodelling. This dominant bone formation could result in the improvement in cortical bone striations and the increase in bone mineral density of trabecular bone.

Adolescent↗
PubMed1997

Longitudinal changes of metacarpal cortical striation in Graves' disease.

RATIONALE AND OBJECTIVES: The authors verify whether metacarpal cortical striation can be used to assess longitudinal changes in bone turnover in Graves' disease. METHODS: Eight patients with untreated Graves' disease (5 men, 3 women; age 36 +/- 12 years) and six patients with the disease in remission (1 man, 5 women; age 38 +/- 12) were studied. Posteroanterior radiographs of the bilateral hands were obtained using fine-grain mammography film and direct magnification. Three observers independently determined the grade of cortical striation (striation index; SI) of the second and third metacarpals in randomly presented radiographs. RESULTS: The SI determined by all observers decreased significantly after the beginning of antihyperthyroid therapy compared with the SI before treatment (P < 0.05). Significant correlation was found between the observers' assessments (r = 0.74, P < 0.001). The average kappa value and percent agreement were 0.27 and 51.8%, respectively. Intraobserver variability provided relatively good kappa statistics (kappa: 0.56; percent agreement: 79.9%). Longitudinal decrease in the SI was in accordance with a decline in urinary pyridinoline cross-link excretion, a decline in serum osteocalcin, and an increase in bone mineral density of lumbar spine. CONCLUSIONS: The change in the SI can be used to detect increased and decreased bone turnover. Thus, the SI can be used as one index of bone turnover in patients with Graves' disease.

Absorptiometry, Photon↗
PubMed1997

Methionine sulfoximine, a glutamine synthetase inhibitor, attenuates increased extracellular potassium activity during acute hyperammonemia.

Hyperammonemia causes glutamine accumulation and astrocyte swelling. Inhibition of glutamine synthesis reduces ammonia-induced edema formation and watery swelling in astrocyte processes. Ordinarily, astrocytes tightly control extracellular K+ activity [K+]e. We tested the hypothesis that acute hyperammonemia interferes with this tight regulation such that [K+]e increases and that inhibition of glutamine synthetase reduces this increase in [K+]e. Ion-sensitive microelectrodes were used to measure [K+]e in parietal cortex continuously over a 6-h period in anesthetized rats. After i.v. sodium acetate infusion in eight control rats, plasma ammonia concentration was 33 +/- 26 mumol/L (+/- SD) and [K+]e remained stable at 4.3 +/- 1.6 mmol/L. During ammonium acetate infusion in nine rats, plasma ammonia increased to 594 +/- 124 mumol/L at 2 h and to 628 +/- 135 mumol/L at 6 h. There was a gradual increase in [K+]e from 3.9 +/- 0.7 to 6.8 +/- 2.7 mmol/L at 2 h and 11.8 +/- 6.7 mmol/L at 6 h. In eight rats, L-methionine-D,L-sulfoximine (150 mg/kg) was infused 3 h before ammonium acetate infusion to inhibit glutamine synthetase. At 2 and 6 h of ammonium acetate infusion, plasma ammonia concentration was 727 +/- 228 and 845 +/- 326 mumol/L, and [K+]e was 4.5 +/- 1.9 and 6.1 +/- 3.8 mmol/L, respectively. The [K+]e value at 6 h was significantly less than that obtained with ammonium acetate infusion alone but was not different from that obtained with sodium acetate infusion. We conclude that acute hyperammonemia impairs astrocytic control of [K+]e and that this impairment is linked to glutamine accumulation rather than ammonium ions per se.

Ammonia↗
PubMed1997

Analysis of 372 patients with Crush syndrome caused by the Hanshin-Awaji earthquake.

OBJECTIVE: To clarify clinical features and determine the severity of injuries in patients with crush syndrome in Hanshin-Awaji earthquake. METHODS: We retrospectively reviewed medical records of 6,107 patients hospitalized in 95 hospitals, and identified 372 patients with crush syndrome. RESULTS: The major sites of crush injury were in the lower extremities (74%), followed by the upper extremities (10%), and the trunk (9%). Pelvic fractures, limb fractures, and abdominal injuries were the most frequently associated injury. Patients with trunk compression and/or with abdominal injury had a higher mortality rate. A total of 50 patients (13.4%) died. The causes of death within 5 days after the earthquake were hypovolemia and hyperkalemia. Peak serum creatine kinase concentration increased with the number of crushed extremities. Mortality and the risk of acute renal failure were higher in patients with creatine kinase concentration more than 75,000 micro/L. CONCLUSIONS: Peak serum concentration of creatine kinase as well as the number of injured extremities serve to estimate the severity of crush syndrome.

Abdominal Injuries↗
PubMed1997

Inhibition of azoxymethane-initiated colon tumor by bovine lactoferrin administration in F344 rats.

The influence of bovine lactoferrin (bLF) on colon carcinogenesis was investigated in male F344 rats treated with azoxymethane (AOM). Following three weekly injections of AOM, the animals received 2 or 0.2% bLF for 36 weeks. No effects indicative of toxicity were noted, but significant reduction in both the incidence and number of adenocarcinomas of the large intestine was observed with both doses. Thus, the incidences of adenocarcinomas in the groups receiving 2% and 0.2% bLF were 15% and 25%, respectively, in contrast to the 57.5% control value (P < 0.01 and P < 0.05, respectively). The results indicate that bLF might find application for chemoprevention of colon cancer.

Adenocarcinoma↗
PubMed1997

[Development of an experimental rat model of intraabdominal abscess by Escherichia coli alone. I. Materials for abscess formation].

To develop a new animal model of intraabdominal abscess by Escherichia coli alone, we reevaluated anaerobes and other additions which had been believed necessary to produce an intraabdominal abscess. We took the method of bacterial implantation by insertion of a double gelatin capsules containing microbes and the additions into the peritoneal cavity of male Wister rats. We examined the requirement of causative bacteria for an abscess including both aerobes and anaerobes, sterilized feces, and barium sulfate. It has been proven that a simple and well reproducible intraabdominal abscess can be developed without fail at the seventh day after inoculation although anaerobic bacteria, sterilized feces, and barium sulfate are not used. However, we have failed to produce an abscess without sterilized gauze fiber which should be a core of an abscess and is used instead of sterilized feces. This animal model will contribute to a major simplification of the original one heretofore in use, and is expected to serve as an aid to elucidate the mechanisms of abscess formation.

Abdominal Abscess↗
PubMed1997

[Development of an experimental rat model of intraabdominal abscess by Escherichia coli alone. II. Interactions between an intraabdominal abscess and a host].

It has been demonstrated that an intraabdominal abscess by Escherichia coli alone can be developed without fail although anaerobes or barium sulfate are not used. We investigated the properties and the influence of this abscess on the host. We took the method of bacterial implantation by insertion of a double gelatin capsules containing Escherichia coli suspension of which concentration was adjusted to five grades into the peritoneal cavity of Wister rats. Abscesses were developed in the survived rats on which live bacteria had been inoculated. Only Escherichia coli were found in these abscesses by culture whereas no death was occurred and no abscess was developed in the rats on which no bacterium or heat-killed ones had been inoculated. As for non-survivors at the 7th postoperative day, all of them died of panperitonitis and no abscess was developed. An abscess was developed without fail when live bacteria of which number within the order of 10(7) colony forming units were inoculated. Blood endotoxin concentration 24 hours after inoculation increased exponentially according to the inoculum size. However, that at the 7th postoperative day returned to the levels at zero time. Microscopic examination revealed a thick abscess wall, poor infiltration of inflammatory cells, and poor neovascularsis into the wall. These findings suggest that endotoxin is prevented from release into the blood stream since abscess contents are isolated by thick wall.

Abdominal Abscess↗
PubMed1997

Gene expression of PDGF and PDGF receptor in various forms of glomerulonephritis.

Platelet-derived growth factor (PDGF) is an important mitogenic factor for various cells. In order to elucidate the role of PDGF in the development of human glomerulonephritis, we examined the gene and protein expression of the PDGF-B chain (PDGF-B) and PDGF-beta receptor (PDGFR-beta) in renal biopsy specimens from patients with various forms of glomerulonephritis using a nonradioactive in situ hybridization and an immunohistochemical technique. The mRNA expression of PDGF-B and PDGFR-beta was significantly increased in the glomeruli of patients with mesangial proliferative glomerulonephritis (IgA nephropathy, Henoch-Schönlein purpura nephritis, and lupus nephritis) compared with those in normal glomeruli. In cases with increased protein expression of PDGF-B and PDGFR-beta, each mRNA expression was also increased. The degree of glomerular injury was positively correlated with the number of mRNA-positive cells for both PDGF and PDGF receptor. There was also a positive correlation between the number of mRNA-positive cells for PDGF-B and PDGFR-beta. PDGF-B and PDGFR-beta were also expressed on cells of the capillary wall, cellular crescents and infiltrated cells in the interstitium. The results suggest that PDGF acts as an important and common mediator for the development of various forms of human mesangial proliferative glomerulonephritis. Furthermore, PDGF may participate in crescent formation and tubulo-interstitial injury.

Adolescent↗
PubMed1997

Effect of NMDA receptor antagonists on protein kinase activated by chronic morphine treatment.

In a previous study we indicated the involvement of the N-methyl-D-aspartate (NMDA) receptor in the development of morphine dependence as assessed by naloxone-induced rise in norepinephrine release in chronically morphine-treated rats. In the present experiments, we studied (1) the possible role of protein kinases in the increased norepinephrine release occurring after naloxone injection and (2) the effects of NMDA receptor antagonists on chronic morphine exposure-induced changes in protein kinase activity. The naloxone-induced rise in norepinephrine release was attenuated by concomitant administration of a protein kinase inhibitor, 1-(5-isoquinolinesulfonyl)-2-methylpiperazine hydrochloride (H-7) or an NMDA receptor antagonist, (+)-5-methyl-10, 11-dihydro-5H-dibenzo[a,d]-cyclohepten-5, 10-imine hydrogen maleate (dizocilpine, MK-801) with morphine. Both cAMP-dependent protein kinase (PKA) and protein kinase C (PKC), which mediate neurotransmitter release, were clearly activated in the cytosol of the pons/medulla, but not in that of the hippocampus, in chronically morphine-treated rats. This activation of PKA and PKC by chronic morphine treatment was inhibited by infusion of dizocilpine or D(-)-2-amino-5-phosphonopentanoic acid (AP-5), an ionotropic glutamate receptor antagonist, together with morphine. These results suggest that NMDA receptor antagonists inhibit the increase in protein kinase activity produced by chronic morphine treatment, thus suppressing the naloxone-induced rise in norepinephrine release.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1997

Increased expression of intercellular adhesion molecule-1 (ICAM-1) in diabetic rat glomeruli: glomerular hyperfiltration is a potential mechanism of ICAM-1 upregulation.

Mononuclear cells, including monocytes/macrophages and T-cells, are considered to be involved in the progression of diabetic nephropathy, although the mechanism of their recruitment into diabetic glomeruli is unclear. The intercellular adhesion molecule-1 (ICAM-1) promotes the infiltration of leukocytes into atherosclerotic lesions as well as inflammatory tissues. In the present study, we investigated the expression of ICAM-1 in the glomeruli of streptozotocin-induced diabetic rats. The expression of ICAM-1 was increased significantly during the early stage of diabetes. The number of mononuclear cells, primarily monocytes/macrophages and lymphocytes, was significantly increased in diabetic glomeruli. Mononuclear cell infiltration into diabetic glomeruli was prevented by anti-ICAM-1 monoclonal antibody. Insulin treatment decreased ICAM-1 expression and mononuclear cell infiltration. The ICAM-1 expression on cultured human umbilical vein endothelial cells was not induced under high glucose culture conditions. Glomerular hyperfiltration is a characteristic change in the early stage of diabetic nephropathy. Treatment with aldose reductase inhibitor, which prevented glomerular hyperfiltration without changes in blood glucose levels, decreased ICAM-1 expression and mononuclear cell infiltration. Moreover, we examined the ICAM-1 expression in the glomeruli of the 5/6 nephrectomized rat, which is a model for glomerular hyperfiltration without hyperglycemia. The ICAM-1 expression and infiltration of mononuclear cells was significantly increased in the glomeruli of 5/6 nephrectomized rats. We conclude that ICAM-1 is upregulated and promotes the recruitment of mononuclear cells in diabetic glomeruli. Moreover, glomerular hyperfiltration that occurs in the early stage of diabetic glomeruli may be one of the potential mechanisms of ICAM-1 upregulation in diabetic nephropathy.

Aldehyde Reductase↗
PubMed1997

Estimation of age from teeth by amino acid racemization: influence of fixative.

To determine the age of a subject from teeth accurately utilizing the racemization rates of amino acids, standard samples of the same tooth species from the same jaw are necessary as controls, as well as data for identification. However, standard teeth are generally stored in fixatives such as ethanol and formalin. We investigated and compared the degree of progression of racemization of dentinal aspartic acid in teeth stored in 95% ethanol, 10% formalin, or 10% neutral formalin fixatives. The racemization rate of dentinal aspartic acid in teeth stored in 10% neutral formalin was the highest, followed by that for teeth stored in 10% formalin then that for teeth stored in 95% ethanol. Teeth stored in these fixatives at 15 degrees C showed almost no progression of racemization. The racemization ratio (D/L ratio) in teeth extracted 10 years previously was almost unchanged from that at the time of extraction, and allowed an accurate evaluation of the subjects age at tooth extraction.

Age Determination by Teeth↗
PubMed1997

Changes in serum concentrations of matrix metalloproteinases, tissue inhibitors of metalloproteinases and type IV collagen in patients with various types of glomerulonephritis.

One of the major causes of glomerular sclerosis which precedes renal failure is an increase in glomerular extracellular matrices (ECMs). Glomerular ECMs which are composed of mesangial matrix and basement membrane play an important role in physical, mechanical and structural functions of the glomerulus. Matrix metalloproteinases (MMPs) are the enzymes which degrade both the collagenous and noncollagenous components of the ECMs. Tissue inhibitors of metalloproteinases (TIMPs) are inhibitors of MMPs. The regulations by MMPs and TIMPs are considered to contribute to maintain homeostasis in the production and degradation of ECMs in the glomeruli. In the glomeruli of patients with glomerulonephritis, the imbalance between production and degradation of ECMs is supposed to cause the increase in ECMs and glomerular sclerosis. In this study, serum concentrations of MMP-1, -2, and -3, TIMP-1 and 2 and type IV collagen were measured in patients with IgA nephropathy, lupus nephritis and membranous nephropathy. In patients with IgA nephropathy and lupus nephritis which are mesangial proliferative glomerulonephritis, the levels of MMP-3 and TIMP-2 were increased. On the other hand, the levels of type IV collagen, MMP-2 and TIMP-1 were increased in patients with membranous nephropathy in which the thickening of basement membrane is characteristic. These differences may be caused by the difference of the pathogenesis of these diseases. The present results suggest that the imbalance between the metabolism of ECMs occurs in patients with glomerulonephritis and contributes to the progression of glomerulonephritis.

Adult↗