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T Shimazu

Publications and source records attributed to T Shimazu.

At least 73 records · Page 4Linked to original sources
PubMed1999

L-Glutamate and insulin enhance glycogen synthesis in cultured astrocytes from the rat brain through different intracellular mechanisms.

The effects of L-glutamate and insulin on glycogen synthesis in astrocytes were examined. L-Glutamate and insulin both stimulated glycogen synthesis in primary cultures of rat astrocytes in a dose-dependent manner, as measured by the incorporation of 14C from [14C]glucose into glycogen. D-Aspartate also increased the incorporation of 14C into glycogen. When insulin and L-glutamate were added together, the glycogen synthesis as well as glycogen content of the cells was additively increased. Wortmannin, an inhibitor of phosphatidylinositol 3-kinase, had little effect on glycogen synthesis induced by L-glutamate, whereas it suppressed the insulin-induced glycogen synthesis. These results suggest that the insulin- and L-glutamate-induced glycogen syntheses are mediated by different intracellular mechanisms. In fact, insulin stimulated the conversion of glycogen synthase b to glycogen synthase a, which was suppressed by wortmannin. L-Glutamate and D-aspartate, however, did not increase the level of glycogen synthase a activity. By contrast, L-glutamate increased 2-deoxy-D-[3H]glucose uptake by the astrocytes, whereas insulin did not affect the uptake. These results suggest that insulin stimulates glycogen synthesis in astrocytes by activating glycogen synthase, which is dependent on a wortmannin-sensitive signaling pathway. L-Glutamate, however, enhances the glucose uptake, which contributes to the increase in glycogen synthesis in the cells.

Androstadienes↗
PubMed1999

Complex hprt deletion events are recovered after exposure of human lymphoblastoid cells to high-LET carbon and neon ion beams.

Hypoxanthine phosphoribosyltransferase gene (hprt) mutations were induced in human TK-6 lymphoblastoid cells by irradiation at a linear energy transfer (LET) of 250 or 310 keV/micron for carbon and neon ions, respectively. At such a high level of LET, ions will lose most of their total energy and stop shortly after passing through the cell. The hprt mutations were analyzed by multiplex PCR, long-PCR and DNA sequencing of both genomic and cDNA. Over half of the C ion-induced hprt mutations (10 of 19) were point mutations, in contrast to 15% of the mutations induced by Ne ions (three of 20). The remaining 47 and 85% of the C and Ne ion-induced mutants, respectively, are deletion events. The latter events include three complex losses of multiple non-contiguous exon regions in both ion irradiation collections. We note that mutations involving the exon 6 region are frequent in the Ne ion collection: all three of the complex events retained the exon 6 region with flanking deletion of sequence and three other mutants involved deletion of this region. It may be concluded that these high-LET C and Ne ion irradiations produce different mutational spectra.

Carbon↗
PubMed1999

Does growth hormone augment brain edema caused by brain injury? A study with a freeze brain injury model in the rat.

OBJECTIVE: Because of the known sodium and water retention associated with growth hormone (GH) therapy, it is crucial to evaluate the safety of GH after brain injury. To clarify this issue, we investigated whether GH affects brain edema in a rat brain freeze-injury model. METHODS: Male Wistar rats (n = 29) were divided into four groups according to the substance injected (GH vs. normal saline) and whether the brain was injured or not. The subcutaneous injections of GH (0.8 IU/kg) or saline were given 24 hours apart. In the injury groups, after the second injection, an aluminum rod (4-mm diameter) cooled to -50 degrees C was placed on the exposed dura mater in the right parietal region for 4 minutes, under anesthesia. At 4 hours after the insult, brain and skeletal muscle were excised and their water content was measured by drying. RESULTS: Freeze injury of the brain caused an increase in water and sodium content in skeletal muscle. GH injection augmented this edema in skeletal muscle. Freeze injury of the brain also caused an increase in water and sodium content in the injured hemisphere of the brain. GH injection did not exacerbate this edema in injured brain tissue. Neither freeze injury nor GH injection caused brain edema in the noninjured hemisphere or in the cerebellum. CONCLUSION: GH administration did not augment brain edema caused by brain injury in our model.

Animals↗
PubMed1999

Priming, second-hit priming, and apoptosis in leukocytes from trauma patients.

BACKGROUND: Polymorphonuclear leukocytes (PMNL) play important roles in both host defenses and systemic inflammatory responses after insults. The objectives of this study are to examine the serial changes in PMNL priming and apoptosis in severely injured patients and to evaluate the impact of second hits on primed PMNL function and systemic vascular endothelial damage. METHODS: Twenty-four severely injured patients (mean Injury Severity Score, 31.1 +/- 9.7) were included. Infections were seen as second hits after trauma in seven patients. Oxidative activity, phagocytosis, and apoptosis of PMNL from serial blood samples were measured by flow cytometry. Oxidative activity with no stimulus and with formylmethionyl-leucyl-phenylalanine (FMLP) were analyzed as the priming index and FMLP response, respectively. Interleukin (IL)-6, IL-10, PMNL elastase, and thrombomodulin concentrations in blood were also measured before and after the second hit. RESULTS: The PMNL priming index was elevated from days 2 to 13, especially days 2 to 5 after injury. FMLP response was enhanced from days 2 to 21 after injury. Apoptosis of PMNL was inhibited for as long as 3 weeks after injury. Infections as second hits after trauma enhanced both the priming index and the FMLP response within 24 hours after diagnosis of infection and increased serum IL-6 concentrations. However, serum thrombomodulin levels were not affected by second hits. All patients with second hits survived. CONCLUSION: Severe trauma stimulated acute-phase priming in PMNL and inhibited apoptosis. Infections after trauma induced second-hit priming in PMNL, but the unchanged serum levels of thrombomodulin suggest that priming per se may not cause systemic vascular endothelial damage.

Adult↗
PubMed1999

Granulocyte colony-stimulating factor ameliorates life-threatening infections after combined therapy with barbiturates and mild hypothermia in patients with severe head injuries.

OBJECTIVE: The objective of this study was to clarify the effects of recombinant human granulocyte colony-stimulating factor (rhG-CSF) administration on infections in patients with severe head injuries after combined therapy with high-dose barbiturates and mild hypothermia. PATIENTS AND METHODS: Since 1996, we have administered rhG-CSF to eight patients with severe head injuries for 5 days (group G). Their treatment results were compared with those of 22 patients cared for earlier without rhG-CSF treatment (group N). All patients in both groups met the criteria of total leukocyte count (TLC) less than 5,000/mm3, C-reactive protein (CRP) over 10 mg/dL, and the presence of an infectious complication. Changes in the TLC, CRP, respiratory index, intracranial pressure, and infectious condition were evaluated in both groups. In addition, the nucleated cell count and differentiation from bone marrow aspiration, neutrophil functions, serum concentrations of interleukin-6, and plasma concentration of leukocyte elastase were evaluated in group G. RESULTS: In group G, TLC, nucleated cell count, and neutrophil functions significantly increased, whereas CRP, respiratory index, and interleukin-6 decreased reciprocally. There was no deterioration of intracranial pressure and leukocyte elastase. Consequently, seven of the eight patients in group G recovered from life-threatening infections, and none of the eight patients died. However, in group N, CRP and respiratory index remained high and TLC did not increase as much as it did in group G. Infections continued after 5 days in 17 of the 22 patients, 7 of whom died from severe infections during hospitalization. CONCLUSION: Administration of rhG-CSF ameliorated life-threatening infections without causing lung injury or increasing brain swelling in patients with severe head injuries who were treated with combined therapy involving high-dose barbiturates and mild hypothermia.

Adolescent↗
PubMed1999

Changes in left ventricular performance in patients with severe head injury during and after mild hypothermia.

OBJECTIVE: To evaluate left ventricular (LV) performance in patients with severe head injury during and after mild hypothermia. PATIENTS AND METHODS: Seven consecutive patients who underwent therapeutic mild hypothermia (age, 15 to 70 years; Glasgow Coma Scale score on admission, 4 to 8). LV performance was assessed by using M-mode, color tissue Doppler imaging tracings and pulsed Doppler echocardiography. LV contraction and relaxation were evaluated by using the peak velocity of LV posterior wall movement during systole (Smax) and diastole (Dmax), respectively, in addition to the conventional echocardiographic indices. RESULTS: Mild hypothermia increased LV ejection time and reciprocally reduced LV filling period as indicated by temperature-dependent shortening of the early diastolic filling and the total diastolic inflow time. The indices depending on temporal factors such as ejection time, Smax, or Dmax were significantly affected by mild hypothermia, whereas those depending on spatial factors such as fractional shortening or stroke volume index were not. The attenuated Smax was compensated for the prolonged ejection time resulting in the relatively consistent fractional shortening regardless of body temperature. There was no compensatory mechanism for the decreased Dmax during diastole. CONCLUSION: The effect of mild hypothermia seemed to be predominantly negatively chronotropic. LV diastolic function was more vulnerable to mild hypothermia than LV systolic function was.

Adolescent↗
PubMed1999

STS-95 Space Experiments (plants and cell biology).

We report the outline of Space Experiments conducted on Space Shuttle (STS-95) launched in autumn of 1998. In this STS-95 mission, Japanese astronaut Dr. Chiaki Mukai achieved her 2nd space flight and conducted a part of 82 space experiments including Japanese experiments. US astronaut Senator John Glenn also achieved his second space flight, 36 years after his first space flight. Senator Glenn was a leader of the original (the first) 7 US astronauts and very famous in US because he succeeded US first orbital space flight around the earth. NASDA had started the project of space experiment using STS-95 at the summer of 1997, therefore we had only one year for the all preparation Yamashita, et al. Biological Sciences in Space, Vol.12 No.3(1998). Scientific results will be reported by investigators, therefore we report here how we had been developing the space experiment plan, on board operation procedure and ground operations including ground control experiments about four plant experiments and one cell biology experiment.

Biological Science Disciplines↗
PubMed1999

Microinjection of leptin into the ventromedial hypothalamus increases glucose uptake in peripheral tissues in rats.

We studied the effects of microinjection of leptin into the ventromedial hypothalamus (VMH) and lateral hypothalamus (LH) on glucose uptake in peripheral tissues in unanesthetized rats. The rate of glucose uptake was assessed in vivo by 2-[3H]deoxyglucose incorporation. Single injection of leptin into VMH increased glucose uptake in brown adipose tissue (BAT), heart, skeletal muscles, and spleen but not in white adipose tissue or skin. On the other hand, microinjection of leptin into LH had little effect on glucose uptake in those tissues. The plasma concentrations of glucose and insulin were unaltered by intrahypothalamic injection of leptin into either VMH or LH. Among skeletal muscles, the increase in glucose uptake induced by intrahypothalamic injection of leptin was greater in the soleus than in the extensor digitorum longus. Likewise, the increased glucose uptake in the gastrocnemius in response to leptin was more prominent in the red part than in the white part of the tissue. When surgical sympathetic denervation of the interscapular BAT was performed, the enhanced glucose uptake by BAT in response to intrahypothalamic leptin was completely suppressed. These findings suggest that intrahypothalamic injection of leptin preferentially increases glucose uptake by some peripheral tissues through activation of the VMH-sympathetic (or its neighboring medial hypothalamus-sympathetic) nervous system, thereby contributing to the maintenance of energy balance.

Adipose Tissue, Brown↗
PubMed1999

Role of the sympathetic nervous system and insulin in enhancing glucose uptake in peripheral tissues after intrahypothalamic injection of leptin in rats.

Our previous study demonstrated that microinjection of leptin into the ventromedial hypothalamus (VMH) dramatically increased glucose uptake in the heart, brown adipose tissue (BAT), and skeletal muscles, but not in white adipose tissue (WAT) in conscious unrestrained rats, as assessed in vivo by the 2-[3H]deoxyglucose method. Here we examined the role of the sympathetic nervous system and insulin in enhanced glucose uptake by tissues after hypothalamic leptin injection. Pretreatment with guanethidine significantly suppressed the increased glucose uptake by the tissues in response to leptin injected into the VMH, whereas bilateral adrenal demedullation had no significant effect. Treatment with propranolol but not phenoxybenzamine also decreased significantly enhanced glucose uptake by the tissues. We further examined the interaction of the effects of hypothalamic leptin and insulin administered peripherally by clamping the glucose concentrations at a constant level. When leptin was injected into the VMH and a maximal dose of insulin was administered intravenously, the rates of glucose uptake by the heart, BAT, and skeletal muscles, but not by WAT, markedly increased beyond the values reached by insulin stimulation alone. Surgical sympathetic denervation of BAT abolished the enhancement of glucose uptake in this tissue, decreasing to the level stimulated by insulin alone. These results appear to indicate that leptin in the hypothalamus enhances glucose uptake in certain peripheral tissues through mediation of a beta-adrenergic mechanism for the sympathetic nerves innervating the tissues and that central leptin and peripheral insulin have a synergistic role in augmenting tissue glucose uptake.

Adipose Tissue↗
PubMed1999

Little benefit from mild hypothermia therapy for severely head injured patients with low intracranial pressure.

OBJECT: This study was performed to determine whether mild hypothermia therapy is essential for the treatment of severely head injured patients in whom intracranial pressure (ICP) can be maintained below 20 mm Hg by using conventional therapies. METHODS: Sixteen consecutive severely head injured patients fulfilled the following criteria: the patient's ICP was maintained below 20 mm Hg by using fluid restriction, hyperventilation, and high-dose barbiturate therapy; and the patient had a Glasgow Coma Scale score of 8 or less on admission. After conventional therapies had been applied, the patients were divided randomly into two groups: the mild hypothermia group (HT group; eight patients) and the normothermia group (NT group; eight patients). The HT group received mild hypothermia (intracranial temperature 34 degrees C) therapy for 48 hours followed by rewarming at 1 degree C per day for 3 days, whereas the NT group received normothermia (intracranial temperature 37 degrees C) therapy for 5 days. Specimens of cerebrospinal fluid (CSF) taken from an intraventricular catheter every 24 hours were analyzed for the presence of excitatory amino acids ([EAAs] glutamate, aspartate, and glycine) and cytokines (tumor necrosis factor-alpha, interleukin [IL]-1beta, IL-6, IL-8, and IL-10). The two groups did not differ significantly in patient age, neurological status, or level of ICP. There were no significant differences in daily changes in CSF concentrations of EAAs and cytokines between the two groups. The incidence of pneumonia was slightly higher in the HT group compared with the NT group (p = 0.059). The incidence of diabetes insipidus associated with hypernatremia was significantly higher in the HT group compared with that in the NT group (p < 0.01). The two groups did not differ with respect to their clinical outcomes. CONCLUSIONS: The authors recommend normothermia therapy for the treatment of severely head injured patients in whom ICP can be maintained at lower than 20 mm Hg by using conventional therapies, because mild hypothermia therapy does not convey any advantage over normothermia therapy in such patients.

Adolescent↗