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H Inaba

Publications and source records attributed to H Inaba.

At least 91 records · Page 5Linked to original sources
PubMed1995

Modulation of protein kinase C produces glucose-dependent alterations in hemodynamics and metabolism in the perfused liver in fasted rats.

Protein kinase C (PKC) has been suggested to be involved in the regulation of hepatic blood flow and metabolism. To confirm the role of PKC, we studied the effects of active and inactive PKC modulators on hemodynamics and metabolism in the perfused rat liver. In addition, the influence of glucose concentration in the medium was studied. The liver was isolated from fasted Sprague-Dawley rats and perfused through the portal vein at a constant pressure of 12 cm H2O. 4 alpha-Phorbol 12,13-didecanoate, an inactive phorbol ester for PKC, slightly decreased hepatic flow only when its initial concentration was raised to 20 microM. In contrast, 4 beta-phorbol 12,13-didecanoate, an active phorbol ester for PKC, at initial concentrations of 80 nM to 1.28 microM decreased hepatic flow and oxygen consumption in a dose-dependent manner, and increased lactate production. HA-1004, a relatively inactive PKC inhibitor, at an initial concentration of 33 microM did not modify the effects of phorbol 12-myristate 13-acetate (PMA), a potent PKC activator. However, H-7, a relatively specific PKC inhibitor, at a concentration of 33 microM attenuated the effects of PMA. The effects of PMA were enhanced by an increase in n-glucose concentration from 10 to 25 mM but not by an increase in L-glucose concentration. These results suggest that modulation of PKC exerts glucose-dependent influences on hepatic flow and metabolism.

Animals↗
PubMed1995

[Kindling of the rat pyriform cortex in the process of aging].

The author investigated seizure susceptibility in 10-12-month-old male sprague-Dawley rats (elderly group) by kindling of the pyriform cortex (PC). Male rats (3-4 mo.) of the same strain were used as the control group. The kindling development of the elderly group was significantly slower than that of the control group because stages 1 and 2, which are indicative of partial seizures, were prolonged. The incidence of regression of seizure stage during the kindling process was higher in the elderly group than in the control group (70% and 40%, respectively), but not significantly. In addition, the elderly group showed a shorter duration of afterdischarges (AD) through the kindling process, and afterdischarge threshold in the PC was slightly elevated in the elderly group as compared with the control group, but not significantly. There were no significant differences between the two groups in the incidence of falling, and in the latency for falling at the first stage 5 seizure (generalized convulsion). The results indicate that the elderly group has difficulty in acquisition of epileptogenesis, while there is no apparent change in the susceptibility to generalized convulsion as compared with the control group.

Aging↗
PubMed1994

Phase I study of E1077, a novel parenteral cephem antibiotic.

The safety and pharmacokinetics of E1077, a new injectable cephem antibiotic, were evaluated in healthy male adult volunteers. In the single-dose studies, 100, 250, 500, 1,000, and 2,000 mg of E1077 were administered by intravenous infusion at a constant rate for 60 minutes, then 1,000 mg of the drug by intravenous infusion at a constant rate for 5 minutes. The Cmax were 6.4, 15.7 +/- 12.0, 34.7 +/- 4.6, 63.2 +/- 4.6, 142.7 +/- 5.6, and 131.6 +/- 36.0 (means +/- SD) micrograms/mL, respectively, and the Cmax and AUC increased linearly with the dose. Plasma concentration-time curves were well described by a two-compartment open model. The plasma elimination half life of the drug was 1.88 +/- 0.15 hours. The mean urinary recovery within the first 24 hours was 94.1 +/- 5.1% of the dose. In the multiple-dose study, 2,000 mg of E1077 was intravenously administered at a constant rate over 60 minutes every 12 hours for 4.5 days (a total of nine times). The Cmax after the first and ninth doses were 134.0 +/- 17.4 and 135.5 +/- 15.5 micrograms/mL, respectively, and trough levels in day 1 and day 5 (at 12 hours after the first and ninth administration, respectively) were 2.2 +/- 0.8 and 1.9 +/- 0.4 micrograms/mL, respectively. No accumulation of the drug in plasma was observed. There were no significant differences in plasma levels or in the urinary recoveries between the single- and multiple-dose regimens.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Pharmacokinetic and pharmacodynamic profiles of CS-518, a selective, long-lasting thromboxane synthase inhibitor, after single and multiple oral administration to healthy volunteers.

A selective thromboxane (TX) synthase inhibitor, CS-518, was orally administered to healthy male Japanese volunteers and the pharmacokinetic and pharmacodynamic properties were investigated. The time profile of drug concentrations in plasma was determined, and the effects of the drug on platelet aggregation in plasma induced by arachidonic acid (AA) and adenosine diphosphate (ADP) ex vivo were examined. The production of TXB2 and 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) in serum during whole blood coagulation ex vivo also were examined. In the single-dose study (50, 100, and 200 mg), plasma concentrations of the drug were well fitted to a one-compartment open model with first-order absorption. The area under plasma concentration curve (AUC) and maximum plasma concentration (Cmax) showed dose-related increases, whereas the mean elimination half-lives remained rather constant (.68-.92 hour). The drug was recovered in urine by 32 to 37% and 62 to 65% as unchanged and conjugated forms (acylglucuronide), respectively, showing almost complete absorption of CS-518. The effect of food intake on the pharmacokinetics of CS-518 was determined at the dose of 100 mg. The time to reach Cmax was prolonged from .42 to 2.08 hours and the Cmax was decreased by about 66%, whereas the AUC and urinary recovery showed no significant changes. The platelet aggregation in plasma induced by AA was markedly inhibited, whereas the secondary aggregation induced by ADP was inhibited to a much less degree. Platelet aggregation by AA was almost completely inhibited 2 hours after administration of any dose and the duration for maintaining the significant inhibition tended to depend on the dose ranging from 48 to 72 hours after administration, which was much longer than expected from the plasma concentration of drug.(ABSTRACT TRUNCATED AT 250 WORDS)

6-Ketoprostaglandin F1 alpha↗
PubMed1994

Suppression by methylprednisolone of augmented plasma endotoxin-like activity and interleukin-6 during cardiopulmonary bypass.

It has been reported that plasma endotoxin, measured by Limulus amoebocyte lysate assays, markedly increased during extracorporeal circulation (ECC). Therefore, this study was undertaken to see if pretreatment with methylprednisolone 30 mg kg-1 modifies the endotoxaemia and associated increases in plasma cytokines in 17 patients undergoing cardiac surgery requiring ECC. We found that methylprednisolone suppressed significantly the ECC-induced increases in plasma endotoxin, measured by a conventional Limulus amoebocyte lysate assay (Toxicolor), and interleukin-6. Plasma concentrations of endotoxin, measured by a highly specific chromogenic Limulus test (Endospecy test), tumour necrosis factor-alpha and interleukin-1 beta did not increase significantly in either the control or methylprednisolone groups.

Adult↗
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

Syalil-SSEA1(SLX) levels in supernatant of cultured human lung carcinoma cell lines.

SLX levels in the culture supernatant of the following 50 cell lines were measured by RIA: pulmonary carcinoma cell lines derived from 46 patients, cell lines of other human cancers derived from 4 patients, and 2 passaged human fibroblast cells as control. Of the 46 pulmonary carcinoma cell lines, 17 (37%) were SLX positive. When the SLX-positive rate was analyzed in relation to the histological type of pulmonary carcinoma, the positive rate was 71% (10/14) for adenocarcinoma, 27% (3/11) for squamous cell carcinoma, 33% (2/6) for large cell carcinoma, 0% (0/11) for small cell carcinoma and 50% (2/4) for adenosquamous cell carcinoma. Analysis of the relationship between tumor cell proliferation and SLX level in 20 patients revealed that the SLX level in the supernatant of SLX-producing cell lines becomes higher in proportion to the increase in the number of these cells. The SLX-positive rate did not differ significantly among different stages of pulmonary carcinoma at the time of tissue collection. There was no significant correlation between SLX production and prognosis. SLX production by each cell line was not correlated with the doubling time of the same cell line in vitro or in vivo (in nude mice). SLX production also showed no correlation with the duration of tumor cell passage.

Adult↗
PubMed1994

Effects of fructooligosaccharides on the absorption of magnesium and calcium by cecectomized rats.

We reported previously that feeding of fructooligosaccharides (FO) increased the apparent absorption of calcium (Ca), magnesium (Mg) and phosphorus (P) in rats. We suggested that there was an important correlation between this phenomenon and fermentation of FO in the large intestine. However, the precise mechanism remained to be characterized. Therefore, we performed a mineral-balance study to identify the segment of lumen in which FO affects mineral absorption, using cecectomized rats. Sham-operated rats and cecectomized rats were fed a control diet (without FO) or an FO-diet (containing 50 g of FO per kg of feed) for 28 days. Feeding of the FO-diet decreased the luminal pH in the cecum and colon in the sham-operated rats. In the cecectomized rats, feeding of the FO-diet also decreased the luminal pH in the colon. Thus, FO was fermented in the colon of the cecectomized rats. However, the acid composition of feces was altered by cecectomy. Feeding of the FO-diet increased the absorption of Ca and Mg in the sham-operated rats. In the cecectomized rats, the FO-diet increased the absorption of Mg but did not increase the absorption of Ca. These results suggest the mechanisms for the absorption of Ca and Mg when rats are fed an FO are different.

Animals↗
PubMed1994

[Antitumor activity of LY 188011, a new deoxycytidine analog, against human cancers xenografted into nude mice].

LY 188011 (gemcitabine hydrochloride) was evaluated for its antitumor effect in fifteen human tumors xenografted in nude mice from seven gastric, two colorectal, two breast, two lung and two liver cancer lines, in the latter four of which the results were compared with those obtained with mitomycin C. LY 188011 significantly reduced the volume of tumor xenografts in seven lines, including drug-resistant colorectal and lung cancer lines. The antitumor effect of LY 188011 was further confirmed by pathological observation. Moreover, LY 188011 has shown to be significantly more potent in two lung cancer models than mitomycin C. Administration of LY 188011 induced less side effect; early loss of body weight was observed in four lines out of fifteen tested. These data suggest that LY 188011 seemed to be an excellent candidate in clinical trials for the treatment of cancer.

Animals↗
PubMed1993

Malignant paraganglioma presenting as Cushing syndrome with virilism in childhood. Production of cortisol, androgens, and adrenocorticotrophic hormone by the tumor.

BACKGROUND: A 12-year-old girl with intractable retroperitoneal paraganglioma experienced increased appetite, acne, obesity, "moon face," and enlargement of the clitoris during the course of the tumor. Plasma cortisol, serum testosterone, and dehydroepiandrosterone sulfate (DHEA-S) levels were increased to 34.1 micrograms/dl, 2.0 ng/ml, and 6.628 ng/ml, respectively. Adrenocorticotrophic hormone (ACTH) levels were not increased, and results of dexamethasone suppression tests were negative. Her condition was diagnosed as Cushing syndrome with virilism. Plasma cortisol levels were increased to a level of 107.1 micrograms/dl before death. METHODS: Tumor samples were obtained at the time of autopsy. The concentrations of cortisol, androgens, ACTH, and catecholamines were assayed in the tumor extracts. The indirect immunoperoxidase procedure was performed on fixed tissues for cortisol, DHEA-S, testosterone, and ACTH. RESULTS: Extracts of the tumor masses contained steroid hormones: the amount of immunoreactive cortisol was 1.64 micrograms/g wet weight; the amount of immunoreactive testosterone was 25.60 ng/g wet weight; immunoreactive DHEA-S, 579.00 ng/g wet weight; and immunoreactive ACTH, 891.00 pg/g wet weight in the metastatic mass of the lung. Immunohistochemically, immunoreactive cortisol, testosterone, and DHEA-S were detectable in the tumor cells. The adrenal gland was atrophic. CONCLUSIONS: The patient is the first reported with malignant paraganglioma with the capacity to produce cortisol, androgens, and ACTH.

Adrenocorticotropic Hormone↗
PubMed1993

Chemiluminescence from bamboo shoot cut.

Bamboo shoot cut emitted weak light, which could be visualized with a two dimensional imaging system. A water extract of bamboo shoot contained tyrosine (a major component of total amino acids), bityrosine and peroxidase. Bamboo shoot peroxidase-H2O2-tyrosine system also emitted weak light with maxima at 490nm, 530nm and longer wavelength, identical to that in horseradish peroxidase-H2O2 system. Judging from these results, chemiluminescence from bamboo shoot cut might be originated from excited species generated by enzymatic oxidation of tyrosine and bityrosine.

Image Processing, Computer-Assisted↗
PubMed1993

Spectrum of mutations in CRM-positive and CRM-reduced hemophilia A.

Hemophilia A is due to the functional deficiency of factor VII (FVIII, gene locus F8C). Although half the patients have no detectable FVIII protein in their plasma, the more rare patients (approximately 5%) have normal levels of a dysfunctional FVIII and are termed cross-reacting material (CRM)-positive. More commonly (approximately 45%), patients have plasma FVIII protein reduced to an extent roughly comparable to the level of FVIII activity and are designated CRM-reduced. We used denaturing gradient gel electrophoresis to screen for mutations within the F8C gene of 11 patients (6 CRM-positive, 5 CRM-reduced) and identified 9 different mutations in 9 patients after analyses of all 26 exons, the promoter region, and the polyadenylation site. Six mutations have not been described previously. Five were missense (Ser289Leu, Ser558Phe, Val634Ala, Val634-Met, Asn1441Lys), and the sixth was a 3-bp deletion (delta Phe652). A review of the literature and the assay of FVIII antigen in 5 hemophilia A patients with previously identified missense mutations from this laboratory yielded a total of 20 other unique CRM-reduced and CRM-positive mutations. Almost all CRM-positive/reduced mutations (24/26) were missense, and many (12/26) occurred at CpG dinucleotides. We examined 19 missense mutations for evolutionary conservation using the portions of the porcine and murine F8C sequences that are known, and 18/19 amino acid residues altered by mutation in these patients were conserved. Almost 50% of mutations (11/26) clustered in the A2 domain, suggesting that this region is critical for the function of FVIII.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
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

Spectra of the formaldehyde-induced ultraweak luminescence from yeast cells.

An increase in the intensity and distinct spectral changes of ultraweak luminescence from the yeast Saccharomyces cerevisiae were measured when the metabolism of cells was drastically altered. A small emission peak and a red emission band 680-850 nm appeared when air-dried cells were imbibed in water. Lethal concentrations of HCHO (0.01%-10%) elicited a 2500 fold increase of the emission intensity and distinct spectral alterations. A transient 500-580 nm emission appeared in the initial phase of interaction. Then a gradually increasing long-lasting red emission band centered around 620 nm predominated in the total spectral range covering 470-850 nm. These emissions were not correlated with minor changes in fluorescence emission and excitation spectra originating from tryptophan, flavins, and unidentified emitters.

Formaldehyde↗
PubMed1993

Modulation of protein kinase C alters hemodynamics and metabolism in the isolated liver in fed and fasted rats.

The activation of protein kinase C (PKC) has been implicated in the pathogenesis of gram-negative sepsis. The effects of PKC modulation on hepatic flow and metabolism were studied using isolated liver perfusion. The liver was isolated from well-fed or overnight-fasted, male Sprague-Dawley rats weighing 250-310 g, and perfused at a constant pressure of 12 cmH2O using a recirculating system. Phorbol 12-myristate 13-acetate (PMA), a potent activator of PKC, decreased hepatic flow and oxygen consumption, and increased net lactate production. It enhanced net glucose production in fed animals. Neither 4 alpha-phorbol didecanoate, an inactive phorbol ester for PKC nor 4 alpha-phorbol, an inactive phorbol had any significant effect. The effects of PMA were augmented by increasing calcium concentration in the medium. PMA at an initial concentration of 4 x 10(-8) M stimulated net lactate and/or glucose production more than a reduction of perfusion pressure from 12 to 6 cmH2O. Staurosporine, a potent PKC inhibitor, significantly attenuated the PMA-induced alterations of hepatic flow and oxygen consumption. These results indicate that modulation of PKC exerts significant effects on hepatic flow and metabolism, which are dependent on extracellular calcium concentrations and feeding conditions, and that the effect of PMA on carbohydrate metabolism is not merely attributed to decreases in hepatic flow and oxygen consumption. It is suggested that PKC activation may be involved in the alterations of hepatic flow and metabolism during severe sepsis.

Alkaloids↗
PubMed1993

Stability of transpedicle screwing for the osteoporotic spine. An in vitro study of the mechanical stability.

The influence of bone mineral density on the stability of transpedicle screwing was studied in the human cadaveric lumbar vertebrae. The pull-out force correlated with bone mineral density. The tilting moment (load needed to tilt the screw 4 degrees cranially at the screw-plate junction) and the cut-up force (load needed to tip the end plate up by the screw) correlated with bone mineral density. A correlation was also found between the maximum insertion torque of the screw and bone mineral density. The maximum insertion torque correlated with the pull-out force, the tilting moment, and the cut-up force. In the cyclic tilting test (200 cycles), the mean value of the tilting moment at the 200th cycle was 67.4 +/- 6.1%, compared with the first cycle. The results suggest that preoperative measurement of BMD is necessary for transpedicle screwing in osteoporotic cases, and that the cyclic tilting motion decrease its mechanical stability. The authors have also concluded that the maximum insertion torque could predict the mechanical stability.

Aged↗