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Biomedical subjects

T Shimazu

Publications and source records attributed to T Shimazu.

At least 109 records · Page 6Linked to original sources
PubMed1997

The beta3-adrenergic agonist BRL37344 increases glucose transport into L6 myocytes through a mechanism different from that of insulin.

In the present study, we examined the effects of BRL37344, a selective beta3-adrenergic agonist, on glucose transport into L6 myocytes and the results were compared with the effects of insulin. Insulin increased 2-deoxyglucose (2-DG) uptake in a dose-dependent manner, with maximal stimulation at 10(-7)M. BRL37344 ranging from 10(-7) to 10(-5)M also enhanced 2-DG uptake in the absence of insulin. The effects of insulin and BRL37344 were completely additive, suggesting that these two agents enhance glucose uptake by L6 myocytes through different mechanisms. In fact, BRL37344 apparently did not increase tyrosine phosphorylation of cellular proteins in L6 myocytes, whereas insulin stimulated tyrosine phosphorylation of 180-190 and 95 kDa proteins. Furthermore, BRL37344-induced increase in glucose transport was not blocked by wortmannin, an inhibitor of phosphatidylinositol 3-kinase, whereas the insulin-induced effect was completely abolished. When L6 myocytes were incubated with insulin, the content of GLUT4 in the plasma membrane was increased. However, BRL37344 did not affect the GLUT4 content in the plasma membrane. BRL37344 did not increase the Vmax value for glucose uptake but decreased the Km value, although insulin increased the Vmax value. These results suggest that BRL37344 enhances glucose transport into L6 myocytes through a signaling pathway different from that of insulin and that the mechanism does not involve the translocation of GLUT4, but may be due to an increase in the intrinsic activity of GLUT present in the plasma membrane.

Adrenergic beta-Agonists↗
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

Fluid resuscitation and systemic complications in crush syndrome: 14 Hanshin-Awaji earthquake patients.

BACKGROUND: Crush syndrome is a form of traumatic rhabdomyolysis characterized by systemic involvement, in which acute renal failure is potentially life-threatening. METHODS: Clinical and laboratory data of 14 crush-syndrome patients transferred to a tertiary emergency department after the Hanshin-Awaji earthquake were analyzed. The patients were buried under collapsed houses for the average of 6.7 +/- 5.7 (SD) hours (range, 1 to 24 hours). They were referred to us 6 to 250 hours after the earthquake. RESULTS: Of those who arrived at our institution within 40 hours, 25% (two of eight) developed renal failure, whereas all six patients who arrived after 40 hours developed renal failure. Peak serum creatine kinase ranged from 6,677 to 134,200 U/L (51,674 +/- 41,776). Renal failure was highly associated with massive muscle damage (serum creatine kinase above 25,000 U/L) and insufficient initial fluid resuscitation (below 10,000 mL/2 days). CONCLUSIONS: Prompt and adequate, if not massive, fluid resuscitation is the key to preventing renal failure after such injury.

Creatine Kinase↗
PubMed1997

Analysis of 2,702 traumatized patients in the 1995 Hanshin-Awaji earthquake.

BACKGROUND: This study was undertaken to define the factors that affected the final outcome of trauma patients in the Hanshin-Awaji earthquake. METHODS: Medical records of patients admitted to 95 hospitals within or surrounding the affected area during the first 15 days after the quake were reviewed. RESULTS: There were 2,702 traumatized patients. One-third of the patients were transported to hospitals in the surrounding area and had a mortality rate of 3%. The remainder, who were treated in the affected hospitals, showed a significantly higher mortality rate (8%; p < 0.05). Intensive care was provided for 513 patients, most of whom suffered from crush syndrome or from injuries to vital organs; these patients had a high mortality rate. Patients with other types of injuries had a lower mortality rate. CONCLUSION: Crush syndrome and injuries to vital organs were potentially life-threatening. We believe that early transportation of such patients to undamaged hospitals with the ability to provide intensive care would have improved the survival rate.

Abbreviated Injury Scale↗
PubMed1997

Activation of mitogen-activated protein kinase by norepinephrine in brown adipocytes from rats.

We have investigated the adrenergic control of mitogen-activated protein kinase (MAPK) activity in brown adipocytes. Cold exposure in rats led to an activation of MAPK in brown adipose tissue, as determined by the gel mobility shift assay and in-gel kinase assay. In contrast, no activation was seen after surgical sympathetic denervation of the tissue. The neurotransmitter, norepinephrine (NE), directly activated MAPK of brown adipocytes in primary cultures in the absence of insulin and serum. NE-induced activation of MAPK was mimicked by beta-adrenergic agonists, including a beta 3-agonist, BRL37344. Activation of MAPK also was observed by an alpha-agonist, phenylephrine, the extent of which being much lower than that by beta-agonists. The effect of NE was attenuated by the beta-adrenergic antagonist, propranolol. Dibutyryl cAMP also mimicked the effect of NE. The phorbol ester, phorbol-12-myristate, 13-acetate(PMA), could induce activation of MAPK, but pretreatment of the cultured cells with PMA to down-regulate protein kinase C did not abolish the ability of NE in activating MAPK. Furthermore, a selective inhibitor of phosphatidylinositol-3 kinase, wortmannin, did not inhibit the effect of NE, whereas insulin-induced activation of MAPK was totally suppressed. These results demonstrate that NE activates MAPK directly in brown adipocytes and that the effect of NE is not mediated by PMA-sensitive protein kinase C or wortmannin-sensitive phosphatidylinositol-3 kinase but rather is likely to be dependent on beta-receptor-mediated increase in cAMP with a minor contribution of alpha-receptor-mediated signals.

Adipose Tissue, Brown↗
PubMed1997

Studies on the response of nitroglycerin oral spray compared with sublingual tablets for angina pectoris patients with dry mouth. A multicenter trial.

Nitroglycerin (glyceryl trinitrate, CAS 55-63-0, NTG) administered with an oral spray may be more effective in relieving anginal pain than sublingual tablets especially when the patient's mouth is dry. In this study, the effect of a NTG oral spray (Myocor Spray) on exercise-induced angina was compared with that of a sublingual tablet in relation to the oral dryness. In 17 patients with effort angina, graded bicycle exercise was performed twice at an interval of one week. Exercise was discontinued upon the onset of moderate anginal pain. Immediately after exercise, the oral dryness was evaluated by touching the tip of the tongue with a blotting paper for a moment. Then, 0.3 mg of NTG was administered by either a squirt of spray or a sublingual tablet in a randomized crossover fashion. Exercise results were reproducible between two exercise tests. According to the extent of the wet area of the blotting paper, the subjects were divided into two groups. In 7 patients of the wet group, the remission times of chest pain and ST segment depression were not significantly different by the formulation of NTG. In 10 patients of the dry group, however, both chest pain and ST depression more rapidly recovered with use of the oral spray (p < 0.05 and p < 0.05, respectively). These results strongly suggest that the NTG oral spray is superior to the sublingual tablet in relieving anginal attacks, when the oral wetness is decreased.

Administration, Sublingual↗
PubMed1996

Noradrenaline increases glucose transport into brown adipocytes in culture by a mechanism different from that of insulin.

Glucose uptake into brown adipose tissue has been shown to be enhanced directly by noradrenaline (norepinephrine) released from sympathetic nerves. In this study we characterized the glucose transport system in cultured brown adipocytes, which responds to noradrenaline as well as insulin, and analysed the mechanism underlying the noradrenaline-induced increase in glucose transport. Insulin increased 2-deoxyglucose (dGlc) uptake progressively at concentrations from 10(-11) to 10(-6) M, with maximal stimulation at 10(-7) M. Noradrenaline concentrations ranging from 10(-8) to 10(-6) M also enhanced dGlc uptake, even in the absence of insulin. The effects of noradrenaline and insulin on dGlc uptake were additive. The stimulatory effect of noradrenaline was mimicked by the beta3-adrenergic agonist, BRL37344, at concentrations two orders lower than noradrenaline. Dibutyryl cyclic AMP also mimicked the stimulatory effect of noradrenaline, and the antagonist of cyclic AMP, cyclic AMP-S Rp-isomer, blocked the enhancement of glucose uptake due to noradrenaline. Furthermore Western blot analysis with an anti-phosphotyrosine antibody revealed that, in contrast with insulin, noradrenaline apparently does not stimulate intracellular phosphorylation of tyrosine, suggesting that the noradrenaline-induced increase in dGlc uptake depends on elevation of the intracellular cyclic AMP level and not on the signal chain common to insulin. When cells were incubated with insulin, the content of the muscle/adipocyte type of glucose transporter (GLUT4) in the plasma membrane increased, with a corresponding decrease in the amount in the microsomal membrane. In contrast, noradrenaline did not affect the subcellular distribution of GLUT4 or that of the HepG2/erythrocyte type of glucose transporter. Although insulin increased Vmax. and decreased the Km value for glucose uptake, the effect of noradrenaline was restricted to a pronounced decrease in Km. These results suggest that the mechanism by which noradrenaline stimulates glucose transport into brown adipocytes is not due to translocation of GLUT but is probably due to an increase in the intrinsic activity of GLUT, which is mediated by a cyclic AMP-dependent pathway.

Adipocytes↗
PubMed1996

Prolonged decrease in hepatic connexin32 in chronic liver injury induced by carbon tetrachloride in rats.

BACKGROUND/AIMS: Our previous study indicated that the amount of connexin32, the major gap-junctional protein of rat liver, is transiently reduced in acute liver injury after single administration of hepatotoxic chemicals. This study was designed to examine alteration in the expression of connexin32 in chronic liver injury, unassociated with hepatocyte proliferation. METHODS: Rats were injected with carbon tetrachloride (CCI4, 0.5 ml/kg) twice a week for 12 weeks. After cessation of CCI4 injection, hepatic contents of connexin32 and its mRNA levels were measured by immunoblotting as well as immunohistochemical examination and by Northern-blot analysis. RESULTS: The plasma alanine-aminotransferase activity was increased from 30 U/I to about 1000 U/l after 12 weeks of CCI4 injections, but recovered nearly to normal level in 7 days after cessation of the injection. Liver specimens 12 days after the last CCI4 injection appeared cirrhotic with a marked increase in fibrosis. Connexin32 contents in these livers decreased to about 37% of controls. The significant decrease in connexin32 content was sustained for at least 30 days and recovered to the control level by 60 days. The alteration of connexin32 content in chronically injured liver was confirmed immunohistochemically. The level of connexin32-mRNA, however, was not reduced, but rather increased by chronic injection of CCI4. CONCLUSION: The results suggest that intercellular communication is disturbed in chronic liver injury, lasting even after recovery from the acute phase of injury. Since the mRNA levels of connexin32 were sustained, the prolonged decrease in connexin32 contents in these livers might be due to a post-transcriptional change that causes decrease in protein synthesis or a derangement of post-translational controls.

Alanine Transaminase↗
PubMed1996

Exaggeration of acute liver damage by hepatic sympathetic nerves and circulating catecholamines in perfused liver of rats treated with D-galactosamine.

Effects of electrical stimulation of the hepatic nerves on acute liver damage were examined using isolated rat liver perfused in situ, 24 hours after intraperitoneal injection with D-galactosamine (800 mg/kg). The leakage of lactate dehydrogenase (LDH) and aspartate aminotransferase (AST) from the liver was used as markers of acute liver damage. In perfused livers after treatment with galactosamine, nerve stimulation (20 V, 20 Hz, 2 ms) increased the leakage of LDH and AST about 3-fold over the basal level accompanied by the decrease in flow rate, whereas with control livers the leakage of LDH and AST into the effluent was almost undetectable throughout the perfusion. The rapid increase in the leakage of LDH and AST was observed during nerve stimulation even under conditions where perfusion flow was maintained constant. Such effects of hepatic nerve stimulation on galactosamine-treated livers were mimicked well by infusion of noradrenaline or phenylephrine, and inhibited by the alpha1-antagonist bunazosin. Artificial reduction of perfusion flow alone did not induce the rapid leakage of LDH and AST into the effluent. On the other hand, low concentration (10 nmol/L) of noradrenaline only minimally decreased the flow rate but apparently augmented liver cell damage. The acute liver damage augmented by noradrenaline was dependent on extracellular Ca2+. These results indicate that in the liver, already having been injured slightly, the activation of hepatic sympathetic nerves and circulating catecholamines exaggerates acute liver damage through an action on liver cells, which depends on the influx of extracellular Ca2+.

Adrenergic alpha-Agonists↗
PubMed1996

Expression of beta3-adrenoceptor and stimulation of glucose transport by beta3-agonists in brown adipocyte primary culture.

Precursor cells of brown adipocytes were isolated from the interscapular brown fat of newborn rats and cultured on collagen-coated dishes. When confluent cells were treated with dexamethasone, mRNAs for muscle/adipocyte type of glucose transporter, hormone-sensitive lipase, and CCAAT/enhancer binding protein alpha were increased remarkably, confirming a predominant effect of dexamethasone on the terminal differentiation of the cultured cells. Effects of dexamethasone on the expression of three subtypes of beta-adrenoceptor were also examined. beta1- and beta2-adrenoceptor mRNAs remained constant regardless of dexamethasone-treatment, while beta3-adrenoceptor mRNA was present only in dexamethasone-treated differentiated cells. To assess the metabolic response mediated by beta3-adrenoceptor, glucose transport into the cells was estimated. Norepinephrine enhanced glucose transport in dexamethasone-treated differentiated cells, but not in undifferentiated cells. beta3-Adrenergic agonists mimicked completely the stimulatory effect of norepinephrine at concentrations lower by two orders of magnitude. These results suggest that the beta3-adrenoceptor is expressed during the course of differentiation in brown adipocytes and plays a significant role in the response of glucose transport to adrenergic stimulation.

Adipose Tissue, Brown↗
PubMed1996

Changes in granulocyte colony-stimulating factor concentration in patients with trauma and sepsis.

OBJECTIVE: To better understand the role of granulocyte colony-stimulating factor (G-CSF) after the inflammatory response. DESIGN: Serum G-CSF concentrations were measured serially in 19 trauma and 15 sepsis patients. Changes in G-CSF concentration were compared with those in the neutrophil ratio, phagocytic and bactericidal activities, and other cytokines. MEASUREMENTS AND MAIN RESULTS: G-CSF concentrations in trauma patients were elevated on day 1, but quickly decreased within 7 days. G-CSF reached its maximum 3 hours after injury, parallel with peaks of interleukin-6 (IL-6) and IL-8, but not of tumor necrosis factor-alpha (TNF-alpha). In sepsis patients, G-CSF as well as TNF-alpha, IL-6, and IL-8 concentrations were markedly elevated at diagnosis and remained high during the course of the illness. These levels decreased significantly in the 11 survivors. Up to 3 days after the trauma, nonsegmented neutrophil ratios were higher than those thereafter. Neutrophil phagocytic and bactericidal activities remained normal during the course of disease in both conditions. CONCLUSIONS: These results suggest that G-CSF plays an important role in the maturation and maintenance of function of neutrophils during the inflammatory response to trauma and sepsis.

Adolescent↗
PubMed1996

Ventilation-perfusion alterations after smoke inhalation injury in an ovine model.

To study the pathophysiological mechanism of progressive hypoxemia after smoke inhalation injury, alterations in ventilation-perfusion ratio (VA/Q) were studied in an ovine model by using the multiple inert gas elimination technique. Because ethane was detected in expired gas of some sheep, we replaced ethane with krypton, which was a unique application of the multiple inert gas elimination technique when one of the experimental gases is present in the inspirate. Severity-related changes were studied 24 h after injury in control and mild, moderate, and severe inhalation injury groups. Time-related changes were studied in controls and sheep with moderate injury at 6, 12, 24, and 72 h. Arterial PO2 decreased progressively with severity of injury as well as with time. In smoke-exposed animals, blood flow was recruited to low VA/Q compartment (0 < VA/Q < 0.1; 17.6 +/- 10.6% of cardiac output, 24 h, moderate injury) from normal VA/Q compartment (0.1 < VA/Q < 10). However, increases in true shunt (VA/Q = 0; 5.6 +/- 2.5%, 24 h, moderate injury) and dead space were not consistent findings. The VA/Q patterns suggest the primary change in smoke inhalation injury to be a disturbance of ventilation.

Airway Resistance↗
PubMed1995

The mechanism of action of hepatic sympathetic nerves on ketone-body output from perfused rat liver. The effect of the interaction of noradrenaline with ATP on the release of beta-hydroxybutyrate.

The regulatory mechanism of ketone-body output by the hepatic sympathetic nerves was studied in rat liver perfused in situ. Enrichment of the perfusion medium with 1 mM octanoate increased the basal ketone-body output from the liver up to 1.5 mumol.min-1.g liver-1. Under these conditions, electrical stimulation of the hepatic nerves (20 V, 20 Hz, 2 ms) decreased the output of both acetoacetate and beta-hydroxybutyrate, and was accompanied by an accumulation of beta-hydroxybutyrate in the liver. The effects of nerve stimulation were inhibited by the alpha 1-antagonist bunazosin (10 microM). However, noradrenaline, a typical sympathetic neurotransmitter, at a concentration of 1 microM decreased the output of acetoacetate but did not affect beta-hydroxybutyrate output. Prostaglandin F2 alpha at a concentration of 10 microM produced an effect similar to treatment with noradrenaline, without a decrease in beta-hydroxybutyrate output. ATP at 50 microM, however, decreased the output of both acetoacetate and beta-hydroxybutyrate and increased the tissue concentration of beta-hydroxybutyrate, mimicking the effect of nerve stimulation. Moreover, in the presence of 0.2 microM ATP, a concentration that produced neither metabolic nor hemodynamic changes, noradrenaline (1 microM) was shown to decrease the beta-hydroxybutyrate output. These results indicate the possible involvement of ATP in the action of hepatic sympathetic nerves on beta-hydroxybutyrate output from the liver, presumably through its interaction with noradrenaline.

3-Hydroxybutyric Acid↗
PubMed1995

Differences in body temperature changes during dressing change in surviving and non-surviving burned patients.

Change in body temperature (delta BT) while dressings were being changed was measured in 52 extensively burned adults. The patients were divided into four groups based on outcome and the prognostic burn index (PBI; age + burn index): group I (15 survivors, PBI less than or equal to 80), group II (15 survivors, PBI between 80 and 120), group III (14 non-survivors, PBI between 80 and 120), and group IV (eight non-survivors, PBI greater than 120). The body temperature before the change of dressings was the same in the four groups. The mean(s.d.) delta BT in all patients was -0.5(0.8) degrees C. The magnitude of delta BT was not related to the time required for changing dressings (r = 0.04) or to the non-epithelialized area present at each change of dressings (r = -0.05). All groups showed a similar increase in delta BT during the early period after the burn, but in group I it began to decrease progressively after the 16th day after the burn (P < 0.05). A reduction in delta BT was noted in group II from day 25, whereas it was unchanged in groups III and IV (P < 0.05). It also significantly increased 2 days before the diagnosis of sepsis (P < 0.05). These results emphasize that delta BT may provide useful information about prognosis and the development of sepsis.

Adult↗
PubMed1995

Low oxygen extraction despite high oxygen delivery causes low oxygen consumption in patients with burns recovering slowly from operative hypothermia.

BACKGROUND: Patients with burns who eventually succumbed to their injuries tended to recover more slowly from operative hypothermia than those who survived. Slower recovery was associated with a lower postoperative oxygen consumption (VO2). We have now investigated whether this was due to impairment of oxygen delivery or extraction. METHODS: This study was performed in 13 adult patients with severely burns. One hundred four measurements of VO2 by indirect calorimetry were made during recovery from 23 episodes of operative hypothermia in 11 patients. Sixty-six measurements of oxygen transport variables by balloon-tipped pulmonary artery catheter were made after 17 episodes of operative hypothermia in six patients. Body temperature was monitored in the urinary bladder. RESULTS: The rate of temperature rise (T) showed a strong positive correlation with VO2 measured both by indirect calorimetry (r = 0.91, p < 0.001) and by balloon-tipped pulmonary artery catheter (r = 0.83, p < 0.001). Oxygen delivery (DO2) was above normal in nearly all patients. Oxygen extraction was low in patients recovering slowly (T < 1.0 degree C/hr) and high in those recovering quickly (T > or = 1.0 degree C/hr). During fast recovery VO2 (373 +/- 77 ml.min-1.m-2; mean +/- SD) was approximately three times normal and was independent of DO2. In contrast, a strong linear relationship existed between VO2 and DO2 during slow recovery (r = 0.76, p < 0.001). CONCLUSIONS: Patients with burns with slow recovery from operative hypothermia exhibited impaired oxygen extraction and dependence of VO2 on DO2 over a wide range. This picture resembles that in patients with critical illness.

Adult↗
PubMed1995

[Immunologic alterations after splenectomy for trauma].

The effects of splenectomy for trauma patients on immunologic function were studied. Various immunologic indices including humoral and cellular immunity were serially measured up to one year in thirteen adult patients with blunt trauma: All the patients recovered from the initial injury and were good health at 12 month except for one died at ten month from unrelated cause. Complements and immunoglobulins decreased following splenectomy, then rapidly increased to normal or above normal levels and maintained the level throughout the one year period. Contrary to previous reports, Ig-M levels were not decreased after splenectomy. Anti-pneumococcal antibody (Pn-ab) was below effective concentration at one year except one case. Lymphocyte subpopulation was characterized by decreased T (OKT-3) cells and inverted helper/suppressor ratio. Lymphocyte blast formation was suppressed before surgery and remained low throughout the period. This study demonstrated that the humoral immunity was reserved after splenectomy, while cellular immunity such as helper/suppressor ratio and lymphocyte blast formation was impaired even one year after injury in most patients. Increased Ig-M levels after splenectomy in this study might suggest different immune response in Japanese. Decreased Pn-ab would justify the use of anti-pneumococcal vaccine after splenectomy for trauma.

Accidents, Traffic↗