Biomedical subjects

T Mizuguchi

Publications and source records attributed to T Mizuguchi.

At least 55 records · Page 3Linked to original sources

PubMed1994

Peripherally administered (6R)-tetrahydrobiopterin increases in vivo tyrosine hydroxylase activity in the striatum measured by microdialysis both in normal mice and in transgenic mice carrying human tyrosine hydroxylase.

The intraperitoneal administration of (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin (6R-BH4), the natural cofactor of tyrosine hydroxylase (TH), increased the accumulation of L-3,4-dihydroxyphenylalanine (DOPA) measured using microdialysis under the inhibition of aromatic L-amino acid decarboxylase by NSD-1015 (in vivo TH activity) in the striatum both of transgenic mice carrying human TH gene and of non-transgenic mice, to a similar extent by about 4-fold. The results indicate that the peripherally administered 6R-BH4 activates in vivo TH activity in the nigrostriatal dopamine neurons in both non-transgenic and transgenic mice.

Animals↗

PubMed1994

Nicotine-induced regulation of tyrosine hydroxylase activity in adrenal gland of transgenic mouse carrying human tyrosine hydroxylase gene.

We investigated the effect of subcutaneous injection of nicotine on in vitro tyrosine hydroxylase (TH) activity in adrenal gland and brain of the transgenic mice carrying an 11-kb fragment containing the entire human TH gene. Injection of 5 mg nicotine/kg (as free base) for 3 days caused a statistically significant increase in vitro TH activity in the adrenal gland, whereas brain TH activity was not affected at all. The adrenal gland of non-transgenic C57BL/6J mice treated in the same way as for transgenic mice tended to enhance TH activity, although not to a significant level. This observation might indicate the possibility that the machinery used by nicotine in regulating the properties or expression of TH in the adrenal gland should be similar between transgenic and non-transgenic mice.

Adrenal Glands↗

PubMed1994

Effects of subacute administration of methamphetamine and nicotine on locomotor activity in transgenic mice expressing the human tyrosine hydroxylase gene.

We produced transgenic (Tg) mice carrying the human tyrosine hydroxylase (TH) gene. To investigate differences in the dopaminergic (DAergic) neuronal activity between the Tg and nTg mice, we examined changes in the locomotor activity induced by methamphetamine (MAP) and nicotine (NIC), which enhances DA release and induces TH enzyme activation, respectively. Surprisingly, however, the intensity of MAP (2.5 mg/kg, once a day for 14 days)-induced hyperlocomotion in the nTg mice was greater than that in the Tg mice, and, furthermore, the Tg mice were less sensitive to subacute administration of NIC (0.5 mg/kg, once a day for 14 days) than the nTg mice. These results suggest that DAergic neuronal function is suppressed in Tg mice to compensate for the overexpression of TH.

Animals↗

PubMed1994

Time-dependent effect of morphine and time-independent effect of MK-801, an NMDA antagonist, on the thermal hyperesthesia induced by unilateral constriction injury to the sciatic nerve in the rat.

BACKGROUND: It is known that peripheral nerve injury induces time-dependent changes in dorsal horn function. The current study investigated the time dependency of the effects of intrathecal morphine and MK-801, an N-methyl-D-aspartate antagonist, on the thermal hyperesthesia evoked by unilateral constriction injury to the sciatic nerve in the rat. METHODS: In rats with a unilateral constriction injury to the sciatic nerve, paw withdrawal latency against thermal stimulation for the injured paw was typically 3 s less than that for the uninjured paw during the first 5 weeks after the injury. Drugs were administered intrathecally 1 or 5 weeks after the nerve injury. RESULTS: Intrathecal morphine increased the paw withdrawal latencies of both the injured paw and the uninjured paw in an equally dose dependent manner in the 1-week study. In the 5-week study, morphine increased the paw withdrawal latency of the uninjured paw in a dose-dependent manner, but not that of the injured paw. Intrathecal MK-801 increased the paw withdrawal latency of the injured paw to the level of the uninjured paw in a dose-dependent manner in both the 1- and 5-week studies. CONCLUSIONS: These data indicate that (1) an N-methyl-D-aspartate receptor-mediated spinal facilitation may be the common mechanism maintaining the thermal hyperesthesia evoked by the constriction injury, and (2) the effects of intrathecal morphine on this thermal hyperesthesia are time-dependent.

Animals↗

PubMed1994

Isoflurane modulates phorbol myristate acetate-, prostaglandin D2-, and prostaglandin E2-induced alterations in hepatic flow and metabolism in the perfused liver in fasted rats.

Protein kinase C (PKC) is thought to play an important role in the regulation of hepatic flow and metabolism in the liver. The activation of PKC has been implicated in pathologic responses of the organisms to immunologically active substances including endotoxin. The effects of volatile anesthetics on the hemodynamic and metabolic alterations associated with PKC activation were studied using isolated liver perfusion. The liver was isolated from overnight-fasted, male Sprague-Dawley rats, and placed in a recirculating perfusion-aeration system. The liver was perfused through the portal vein at a constant pressure of 12 cm H2O. Isoflurane at a concentration of 3% maintained hepatic flow, reduced oxygen consumption, and transiently enhanced lactate production. Phorbol 12-myristate 13-acetate (PMA), a potent activator of PKC, at an initial concentration of 80 nM decreased hepatic flow and oxygen consumption, and enhanced lactate production. Isoflurane significantly attenuated the PMA-induced alterations in hepatic flow, oxygen consumption, and lactate production. A similar inhibition of the PMA-induced alterations was observed in the liver treated with halothane at 2%. Isoflurane attenuated the flow reduction and stabilized the oxygen consumption after the administration of prostaglandin D2 (PGD2) and E2 (PGE2), possible mediators of PMA. Isoflurane, and presumably other volatile anesthetics, may elicit beneficial effects on the liver by attenuating the PKC-mediated alterations in hepatic hemodynamics and metabolism when PKC in the liver is activated through pathologic mechanisms.

Animals↗

PubMed1994

Analysis of the role of endothelin-A and endothelin-B receptors on nociceptive information transmission in the spinal cord with FR139317, an endothelin-A receptor antagonist, and sarafotoxin S6c, an endothelin-B receptor agonist.

Endothelin (ET)-A and ET-B receptors have been reported to exist in the spinal cord but the roles of ET-A and ET-B receptors in the spinal cord are poorly understood. To gain a better understanding of the roles of ET-A and ET-B receptors in nociceptive information transmission in the spinal cord, this study evaluated the effects of ET-1, ET-3, Sarafotoxin S6c (an ET-B receptor-selective agonist) and (R)2-[(R)-2-[(S)-2-[[1- (hexahydro-1H-azepinyl)]carbonyl]amino-4-methyl-pentanoyl]amino-3- [3-(1-methyl-1H-indolyl)]propionyl]amino-3-(2-pyridyl)propionic acid (FR139317, an ET-A receptor-selective antagonist) on the agitation behavior evoked by formaldehyde solution injection and on the thermal nociceptive test. The s.c. injection of formaldehyde solution into the hind paw evoked a biphasic flinching (phase 1, 0-9 min; phase 2, 10-60 min) of the injected paw. For the purpose of data analysis, phase 2 was further divided into two phases (phase 2a, 10-34 min; phase 2b, 35-60 min). Intrathecal injection of ET-1 depressed the phase 1 and 2 flinching behavior in a dose-dependent manner and this ET-1 effect was antagonized by FR139317. Intrathecal injection of either ET-3 or Sarafotoxin S6c enhanced the phase 2a flinching behavior in a dose-dependent manner. Intrathecal injection of the highest doses of ET-1, ET-3 and Sarafotoxin S6c had no effect on the thermal nociceptive test. These data indicate that ET-A and ET-B receptors have a powerful effect on spinal nociceptive processing evoked by formaldehyde solution injection but not that evoked by thermal stimulation.

Animals↗

PubMed1994

[Differential effects of isoflurane, sevoflurane and halothane on autonomic function determined by spectral analysis of heart rate variability].

The effects of isoflurane, sevoflurane and halothane on heart rate variability were studied in 18 patients scheduled for minor otolaryngeal surgery. After the surgery, R-R intervals were determined at minimum alveolar concentrations of 2.0, 1.5, 1.0 and 0.5 under mechanical ventilation. The data were plotted on a one-dimensional map and analyzed further by autoregressive spectral analysis. All three anesthetics suppressed both the low frequency component (Mayer wave related sinus arrhythmia; MWSA) and the high frequency component (respiratory sinus arrhythmia; RSA). The MWSA reflecting sympathetic activity was less affected by sevoflurane while the RSA reflecting parasympathetic function was less influenced by halothane. The one-dimensional map was useful to visualize the depth of anesthesia.

Adolescent↗

PubMed1993

Effects of intrathecal FK888, a novel dipeptide NK1 receptor antagonist, on the formalin test in the rat.

This study investigates the effects of intrathecally administered FK888, a novel dipeptide NK1 receptor antagonist, on the formalin test in the rat. Subcutaneous formalin induces biphasic episodes of flinching behavior at 0-5 min (Phase 1) and 10-60 min (Phase 2) after treatment. FK888 administered intrathecally 10 min before the formalin injection depresses the Phase 2 flinching behavior in a dose-dependent manner, but not the Phase 1 flinching behavior. FK888 has no effect on the Phase 2 flinching behavior when administered intrathecally 60 min before or 9 min after the formalin injection. Intrathecally administered FK888 has no effect on the motor function. These results suggest that FK888 is good drug to study the role of the NK1 receptor in the spinal cord of the rat.

Animals↗

PubMed1993

Effect of erythroid differentiation factor on maintenance of human hematopoietic cells in co-cultures with allogenic stromal cells.

The effect of erythroid differentiation factor (EDF) on the maintenance of human hematopoietic progenitors in a microenvironment was examined by co-culture of adherent- and E rosette-depleted mononuclear cells from the bone marrow (BM) or peripheral blood (PB) with allogenic stromal cells. EDF had no effect on colony formation of erythroid burst-forming units (BFU-E) from the BM cultured without a stromal layer. The number of BFU-E cultured with the stromal layer was decreased less in the presence of EDF than in its absence. This activity of EDF was also observed when the mononuclear cells were separated from the stromal layer by a filter membrane. These data suggest that EDF facilitates maintenance of the number of BFU-E through a humoral factor(s) secreted by the stromal layer. The number of BM erythroid colony-forming units (CFU-E) was decreased on addition of EDF, which promotes differentiation of CFU-E. The number of PB CFU-E was increased irrespective of the presence or absence of EDF over 2 weeks, suggesting that BFU-E, which are more abundant in PB than in BM, differentiate to supply CFU-E. However, the addition of EDF resulted in less increase of PB CFU-E, indicating that it inhibited the proliferation of CFU-E progenitors to suppress colony formation. On the other hand, CFU-GM was consistently decreased by addition of EDF to this culture system. These data indicate that EDF acts as a commitment factor and/or a promoter of erythroid progenitors in a hematopoietic microenvironment.

Activins↗

PubMed1993

Activin A suppresses proliferation of interleukin-3-responsive granulocyte-macrophage colony-forming progenitors and stimulates proliferation and differentiation of interleukin-3-responsive erythroid burst-forming progenitors in the peripheral blood.

We examined the effects of activin A on the proliferation and differentiation of immature hematopoietic progenitors prepared from peripheral blood (PB) using methylcellulose and liquid-suspension culture. In a kinetic analysis, colony formation by PB granulocyte-macrophage colony-forming unit (CFU-GM) was delayed in a dose-dependent manner by the addition of activin A only when stimulated with interleukin-3 (IL-3), but not when stimulated with granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), or stem cell factor (SCF) plus G-CSF. DNA-synthesizing CFU-GM was increased by IL-3, but this effect was abolished by activin A. In contrast, PB erythroid burst-forming unit (BFU-E) was accelerated by the addition of activin A only when exposed to IL-3 plus erythropoietin (Epo), but not when exposed to Epo or Epo plus SCF. DNA-synthesizing BFU-E was increased by IL-3 and activin A, alone and additively in combination. In a mixed culture of myeloid and erythroid progenitors, activin A increased the numbers of BFU-E and CFU-Mix colonies at concentrations of 1 and 10 ng/mL and decreased the number of CFU-GM colonies in a dose-dependent manner. However, in a liquid-suspension culture of erythroid progenitors, activin A decreased total cell count and the percentage of hemoglobin-containing cells only when cells were exposed to IL-3 plus Epo. These results indicate that activin A suppresses the proliferation of IL-3-responsive CFU-GM progenitors and stimulates the proliferation and differentiation of IL-3-responsive BFU-E progenitors, and suggest that activin A acts as a commitment factor of immature hematopoietic progenitors for erythroid differentiation.

Activins↗

PubMed1993

K252a, a potent protein kinase inhibitor, improves endotoxic lethality and glucose dyshomeostasis.

To investigate whether the inhibition of protein kinases including protein kinase C can antagonize endotoxicosis, the in vivo effects of K252a, a potent inhibitor of protein kinases, on endotoxin-induced lethality and glucose dyshomeostasis were determined in conscious rats. Sprague-Dawley rats (260-340 g) were divided into the following four groups: Group DS, 2.5% dimethyl sulfoxide (DMSO), 6 ml/kg iv + 0.9% saline, 2 ml/kg iv; group KS, K252a in 2.5% DMSO, 4 mg/kg iv + 0.9% saline; group DE, 2.5% DMSO + endotoxin (E. coli), 15 mg/kg iv; and group KE, K252a in 2.5% DMSO + endotoxin. A quarter of DMSO or K252a solution was continuously infused over a 15 min period before a bolus injection of either saline or endotoxin. The remaining dose was administered over a 180 min period after saline or endotoxin. All animals in the DS and KS groups survived for 24 hrs. K252a significantly improved endotoxic lethality. It attenuated the initial hyperglycemia, and late hypoglycemia, hyperlactacidemia, and base deficit after endotoxin. However, K252a had no influence on the endotoxic alterations of blood pressure, PaCO2 or PaO2. These results suggest that the activations of protein kinases, particularly protein kinase C, are involved in the pathogenesis of lethal endotoxicosis and sepsis.

Animals↗

PubMed1993

Modification of hepatic protein kinase C with phorbol myristate acetate and staurosporine alters hemodynamics in the perfused rat liver.

Activation of protein kinase C (PKC) has been implicated in the pathogenesis of endotoxicosis and severe sepsis. Since hepatic blood flow and metabolism have been known to be altered in endotoxicosis and sepsis, we studied the hemodynamic effect of PKC modulation with phorbol 12-myristate 13-acetate (PMA) and staurosporine (St) on the perfused rat liver. The liver was isolated from overnight-fasted male Sprague-Dawley rats and placed in a recirculating perfusion apparatus. The liver was perfused with Krebs-Ringer-bicarbonate solution at a constant pressure of 12 cmH2O. Flow to the liver was continuously monitored with an electric magnetic flowmeter. PMA at an initial concentration of 2 x 10(-8) M significantly decreased hepatic flow. Staurosporine (St), a potent PKC inhibitor at 4 x 10(-7) M produced a small increase in hepatic flow. Pretreatment with St significantly attenuated the flow reduction by PMA. St significantly suppressed the flow reductions by 4 x 10(-6) M of prostaglandin E2 and D2. These results suggest that the PKC inside the liver may play an important role in the regulation of hepatic blood flow during endotoxicosis and sepsis.

Journal Article↗

PubMed1993

Prostaglandin E1 (PGE1) attenuates vasoconstriction induced by PGE2, PGD2 and phorbol myristate acetate in the perfused rat liver.

It has been shown that prostaglandins (PGs) produced by Kupffer and endothelial cells play an important role in mediating physiological responses to various immunological stimuli. We studied the effect of prostaglandin E1 (PGE1) on the hemodynamic and metabolic changes induced by prostaglandin E2 (PGE2), D2 (PGD2) and phorbol 12-myristate 13-acetate (PMA), a potent inducer of PGs in the isolated rat liver perfused with Krebs-Ringer-bicarbonate (KRB) solution at a constant pressure of 12 cmH2O. The liver was taken from overnight-fasted male Sprague-Dawley rats weighing 260 to 310 g. Both PGE2 and PGD2 significantly decreased hepatic flow when their initial concentration was elevated to micromolar range. Although 1 x 10(-6) M of PGE1 did not have a major effect on hepatic flow, it significantly attenuated the declines of hepatic flow produced by 4 x 10(-6) M of PGE2 and PGD2. However, none of PGs tested influenced glucose and lactate concentrations in the medium. Continuous infusion of PGE1 into the medium at a rate of 5 microg.min(-1) significantly diminished the decreases in hepatic flow and oxygen consumption induced by 2 x 10(-8) M of PMA. These results suggest that administration of PGE1 may preserve hepatic blood flow by modifying the intrahepatic regulatory mechanism involving the activation of Kupffer and endothelial cells.

Journal Article↗

PubMed1993

Metabolic changes associated with malnutrition in the patients with multiple organ failure.

To clarify the metabolic changes associated with malnutrition in the patients with multiple organ failure (MOF), we measured energy expenditure, nitrogen excretion, nonprotein respiratory quotient (NPRQ), caloric intake, and cumulative caloric balance (CCB) in 20 MOF patients (12 survivors and 8 non-survivors). The non-survivors exhibited significantly greater cumulative caloric deficit than the survivors. Metabolic activity tended to decline to normal in the survivors as organ failures were overcome. In the non-survivors, on the contrary, regardless of large caloric deficit hypermetabolism persisted and characteristically followed by the sudden decrease in metabolic activity at the time immediately prior to death. Compared to the survivors, the non-survivors generally exhibited poorer response in metabolic activity and greater NPRQ change to the altered amount of caloric intake. It seemed that protein sparing effect by increased caloric intake was preserved in both the survivors and the non-survivors only with CCB above -5 times basal energy expenditure. These results suggest that persistent hypermetabolism and poor metabolic response to nutritional support are partly responsible for existing organ failures and poor outcome in MOF patients.

Journal Article↗

PubMed1993

The 5'-flanking region of the human dopamine beta-hydroxylase gene promotes neuron subtype-specific gene expression in the central nervous system of transgenic mice.

Dopamine beta-hydroxylase (DBH, EC 1.14.17.1) catalyzes the conversion of dopamine to norepinephrine, the third step of catecholamine biosynthesis. We have previously created transgenic mice harboring a chimeric gene consisting of the 4-kb DNA fragment of the human DBH gene promoter and the human phenylethanolamine N-methyltransferase (PNMT, EC 2.1.1.28) cDNA, to express PNMT in norepinephrine- and epinephrine-producing cells in the brain, sympathetic ganglia, and adrenal medullary chromaffin cells (Kobayashi et al., Proc. Natl. Acad. Sci. U.S.A., 89 (1992) 1631-1635). In this paper, we produced for the first time the antibody that specifically detects human PNMT, but not mouse PNMT, with the synthetic oligopeptide characteristic of the human PNMT sequence, and used this antibody to investigate the cells expressing human PNMT in transgenic mice. Immunohistochemical analysis of transgenic mice showed typical expression of human PNMT immunoreactivity in norepinephrinergic and epinephrinergic neurons in brain, as well as norepinephrine- and epinephrine-producing cells in the adrenal gland, indicating that the 4-kb 5'-flanking region is essential for the tissue-specific expression of the DBH gene. We also detected the ectopic expression in some DBH-immunonegative cells in the olfactory bulb of transgenic mice.

Amino Acid Sequence↗

PubMed1993

Effect of low-power He-Ne laser on deformability of stored human erythrocytes.

This study was designed to investigate the effect of the He-Ne laser (continuous wave, lambda = 632.8 nm, 8.5 mW in power) irradiation on human erythrocyte deformability. Blood samples were obtained from hematologically normal adult donors by venipuncture. Red cells were washed and adjusted to 30% Ht with 0.9% NaCl solution (pH 7.00). Red cell solution samples were assigned to three groups. Each sample was divided into seven 3-ml working aliquots. The aliquots in Group I were irradiated for 0 (control), 1, 3, 5, 10, 15, and 30 min within 2 hr after sampling. The aliquots in Group 2 and Group 3 were stored at 5 degrees C for 24 and 36 hr, respectively, and received similar irradiations after 12 hr (in both groups), 24 hr (in Group 2), and 36 hr (in Group 3) from sampling. Red cell deformability was measured by the Nuclepore filter filtration and presented as the filter filtration rate (FFR). The deformability shown as FFR was unchanged in Group 1 (fresh cell group) from the control value, but improved significantly in Groups 2 and 3 (damaged cell groups) after the irradiation. These results suggested that the irradiation of low-powered He-Ne lasers improved cytoskeletal protein activities in damaged erythrocytes.

Cytoskeletal Proteins↗

PubMed1993

Do low-power lasers change phase transition temperature of dipalmitoyl phosphatidylcholine (DPPC) membrane?

This study was designed to investigate the effects of the He-Ne laser (632.8 nm of wavelength, 8.5 mW in power, Senko Med. Co. Ltd., Tokyo, Japan) on the phase transition temperature of dipalmitoyl phosphatidylcholine (DPPC) membranes. Liposomal bilayers of DPPC (12.5 mM) were obtained with ultrasonification for 45 min at 40 degrees C and refrigerated for 2-3 days at 5 degrees C. The bilayers vesicle solution was divided into 3-ml working aliquots, which were assigned to three groups. The aliquots in Group 1 were used as controls without irradiation and the aliquots in Groups 2 and 3 were irradiated in 37 degrees C baths for 15 to 30 min, respectively. To determine phase transition temperature, optical density (%T; percent of permittance) of each aliquot was measured spectrophotomechanically at a wavelength of 440 nm while increasing its temperature at a rate of 0.5 degrees C every minute. Main phase transition temperatures in Groups 1, 2, and 3 were 41.54 +/- 0.23 degrees C (n = 10), 41.50 +/- 0.27 degrees C (n = 10), and 41.30 +/- 0.36 degrees C (n = 10), respectively. No significant difference between the nonirradiation and irradiation groups was established. These results suggest that irradiations of low-power He-Ne lasers up to 30 min do not change important physical characteristics of artificial DPPC membranes.

1,2-Dipalmitoylphosphatidylcholine↗

PubMed1993

The effects of morphine, MK-801, an NMDA antagonist, and CP-96,345, an NK1 antagonist, on the hyperesthesia evoked by carageenan injection in the rat paw.

BACKGROUND: The spinal mechanisms underlying the hyperesthetic state during inflammation are little understood. To gain a better understanding of these mechanisms, this study evaluated the effects of intrathecal morphine; MK-801, an N-methyl-D aspartic (NMDA) antagonist; and CP-96,345, an NK1 antagonist, on the hyperesthesia observed after carageenan injection of the rat paw. METHODS: In rats injected with 2 mg carageenan, the paw withdrawal latency (PWL) for the injected paw was typically 5-6 s less than that for the untreated paw, at 2 h after the carageenan injection. Drugs were administered 2 h after the carageenan injection. The magnitude of hyperesthesia was evaluated with the difference score (DS), which was calculated by subtracting the PWL of the untreated paw from the PWL of the injected paw. RESULTS: Intrathecal morphine increased PWLs of both the injected and the untreated paws equally in a dose-dependent manner, but intrathecal morphine did not affect the level of DS. Intrathecal MK-801 increased PWLs of the injected paw to the level of the untreated paw in a dose-dependent manner and increased the DS levels. Intrathecal CP-96,345 had no effect on PWLs of either the injected or the untreated paw. Coadministration of MK-801 with morphine reduced the DS for each dose of morphine. CONCLUSIONS: These data indicate that (1) an NMDA receptor, but not an NK1 receptor, plays an important role in maintaining the hyperesthesia after carageenan injection; and (2) NMDA antagonism has a simple additive interaction with morphine in the carageenan model of inflammatory hyperesthesia.

Animals↗