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Biomedical subjects

S Iwata

Publications and source records attributed to S Iwata.

At least 181 records · Page 10Linked to original sources
PubMed1995

Deterioration of platelet energy metabolism following energy crisis of liver after hepatectomy.

The aim of this study is to investigate the relationship in energy metabolism between the platelet and the liver. The adenylate energy charge of human platelets and arterial ketone body ratio (AKBR:acetoacetate/3-hydroxybutyrate) were measured in 11 patients after hepatectomy. Hepatic energy crisis was defined as the decrease of AKBR below 0.7. The platelet energy charge was measured on the first (Day 1), the second (Day 2), third (Day 3) and sixth (Day 6) day during AKBR decreased and remained under 0.7. The values before AKBR decreased were employed as the control. The values of the platelet energy charge were 0.917 +/- 0.008 in the control (n = 11) and 0.896 +/- 0.009 in all samples after AKBR decreased under 0.7 (n = 30). There was no significant difference between them. The values of energy charge were divided into four groups according to the periods of time after AKBR decreased and remained under 0.7 and compared. The energy charge was 0.923 +/- 0.006 (Day 1, n = 11), 0.907 +/- 0.008 (Day 2, n = 10), 0.890 +/- 0.005 (Day 3, n = 5), and 0.815 +/- 0.012 (Day 6, n = 4). The energy charge of Day 3 was significantly lower than that of Day 1 (p < 0.01). The energy charge of Day 6 was significantly lower than that of Day 1, 2, 3 (p < 0.001, p < 0.001, and p < 0.01, respectively). The 4 patients whose AKBR remained under 0.7 for more than 6 days had hemostatic disorder. The deterioration of the platelet energy charge metabolism lags behind that of the liver.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1995

Decreased energy charge of peripheral blood lymphocytes in septic patients after hepatic resection.

We measured lymphocyte energy charge (LEC) in septic patients after hepatectomy to clarify the energy metabolism of lymphocytes in relation to arterial ketone body ratio (AKBR) reflecting the hepatic mitochondrial redox potential. Sixteen patients with AKBR above 0.7 (state A) tolerated their operations well without postoperative infectious episodes and their LEC (0.895 +/- 0.005, mean +/- SEM) was significantly (p < 0.001) higher than that (0.841 +/- 0.010) of 9 patients with AKBR from 0.7 to 0.4 (state B). Four of the 9 state B patients had multiple organ failure (MOF) with sepsis as a trigger. AKBR in 7 of 9 state B patients decreased and remained below 0.4 (state C). These state C patients showed significantly reduced LEC (0.781 +/- 0.024; p < 0.001, p < 0.05, compared with that in states A and B, respectively) and finally died of MOF with septic state. These results suggest that the severe and prolonged impairment of energy metabolism in the liver may be accompanied with the metabolic derangement of lymphocytes.

Aged↗
PubMed1995

Antitumorigenic activities of chalcones. I. Inhibitory effects of chalcone derivatives on 32Pi-incorporation into phospholipids of HeLa cells promoted by 12-O-tetradecanoyl-phorbol 13-acetate (TPA).

More than forty chalcone derivatives were synthesized to examine their structure-activity relationship against tumorigenesis. As a primary screening test, the inhibitory activities of the chalcones for the 32Pi-incorporation into phospholipids of HeLa cells enhanced by 12-O-tetradecanoyl-phorbol 13-acetate (TPA) were examined. 3-Hydroxy-chalcone derivatives possessing methyl group in 3'-, 4'-, or 2'-position and isoliquiritigenin homologs showed potent inhibitory activities in the phosphorylation test, which suggests their antitumorigenic effects.

Animals↗
PubMed1995

Pharmacological characteristics of the canine cerebrovascular constriction produced by neuropeptide Y.

In order to elucidate the role of neuropeptide Y (NPY) in cerebral circulation, we undertook the present study to examine the action of NPY itself, and the combined effects of NPY with other vasoconstrictor stimuli. NPY itself produced contractions of isolated canine basilar artery in a concentration-dependent manner, which was independent of the presence or absence of endothelium. C-terminal peptides of NPY (NPY12-36) and (NPY22-36) were weak agonists, while those without C-terminals were ineffective. The vasoconstriction produced by NPY was, however, strongly potentiated by increasing the K+ concentration in the medium up to 20 mM, or by pretreatment with tetraethylammonium, a K+ channel blocker and hemolysate containing oxyhemoglobin. NPY also augmented the contractile responses to prostaglandin F2 alpha, norepinephrine, and histamine, but not to serotonin. The contraction in response to NPY per se or in 20 mM K+ was effectively attenuated by Ca2+ antagonists such as d-cis-diltiazem, and in a Ca(2+)-free medium. These results suggest that in canine basilar artery, the activation of the Y1 receptor modulates the availability of the L-type Ca2+ channel, leading to enhance Ca2+ influx from the extracellular space and potentiate contractile effects of other cerebral vasoconstrictors. This might be involved in the cerebral vasospasm which occurs after subarachnoid hemorrhage.

Animals↗
PubMed1995

[Pharmacokinetic and clinical studies with azithromycin (fine granule) in the pediatric field. Pediatric Study Group of Azithromycin].

Azithromycin (AZM) in 10% fine granules, a newly developed azalide antibiotic, was administered at a standard dose of 10 mg/kg once daily for 3 to 5 days (89.5% received 3 day administration) to children with infectious diseases and the efficacy and the safety of AZM were investigated. In addition AZM concentrations were determined in blood samples from 18 patients and in urine samples from 17 patients to examine o pharmacokinetic characteristics of AZM. 1. Absorption and excretion: Cmax's in 16 patients who received 10 mg/kg and 2 patients who received 20 mg/kg were 0.29 +/- 0.24 micrograms/ml and 0.75 micrograms/ml, respectively, while T 1/2's were 42.0 +/- 11.8 hours for the former and 51.3 hours for the latter. AUC(0 to approximately infinity)'s were 10.72 +/- 5.00 micrograms x hr/ml in the former and 28.83 micrograms x hr/ml in the latter. Urinary concentrations of AZM peaked at 48 to 72 hours after the administration of 10 mg/kg AZM in 14 patients, while it peaked at 24 to 48 hours in the patients who received 20 mg/kg. Urinary recovery rates in the first 120 hours after the start were 9.1 +/- 2.6% for 10 mg/kg and 10.8 +/- 3.4% for 20mg/kg. 2. Clinical efficacy: The study received 619 entries and 564 cases were evaluated for drug efficacy. The remaining were not evaluated because of dropout or exclusion. The efficacy rate, combining both "Excellent" and "Good" cases was 94.3% in 246 cases where pathogens were identified, classified as Group A. The efficacy rate was 90.7% for the remaining 321 cases, classified as Group B, where causative pathogens were unidentified. The difference between the two groups was no statistical significance. The combined efficacy rate was 92.2%. For the 116 cases where the patients had failed to respond to previous chemotherapies instituted for 3 days or longer, the efficacy rate for AZM was 94.0%. 3. Adverse reactions and abnormal laboratory tests: Incidents of diarrhea, soft stool, skin rashes, or vomiting were found in 15 patients (2.5%) of 596 cases eligible for evaluation. These reactions, however, were all transient and mild to moderate in severity in the 15 patients including 4 patients for whom the treatment was discontinued, all resolved in time. Abnormal changes in laboratory tests were found as follows: decrease in WBC in 23 patients (5.6%), increase in eosinophils in 28 (7.1%), increase in platelet count in 2 (0.5%), decrease in platelet count in 1 (0.3%), elevation of GOT in 3 (0.8%), and elevation of GPT in 6 (1.6%).(ABSTRACT TRUNCATED AT 400 WORDS)

Absorption↗
PubMed1995

[Pharmacokinetic and clinical studies with azithromycin (capsule) in the pediatric field. Pediatric Study Group of Azithromycin].

Azithromycin (AZM) in 100 mg capsules, a newly developed azalide antibiotic, was administered at a standard dose of 10 mg/kg once daily for 3 to 5 days (89.9% received 3 day administration) to children with infectious diseases and the efficacy and the safety of AZM were investigated. In addition, AZM concentrations were determined in blood samples from 9 patients and in urine samples from 12 patients to examine pharmacokinetic characteristics of AZM. 1. Absorption and excretion: Cmax was 0.45 +/- 0.28 micrograms/ml, T 1/2 was 52.7 +/- 20.2 hours, and AUC(0 approximately to infinity) was 12.09 +/- 4.93 micrograms.hr/ml in the 9 patients each of whom received 8.5 to 14.3 mg/kg AZM. Urinary concentrations of AZM peaked at 48 to 72 hours after the administration of 8.5 to 14.7 mg/kg AZM in 12 patients and the average urinary recovery rate in 120 hours was 7.3 +/- 2.8%. 2. Clinical efficacy: The study received 139 entries and 119 cases were evaluated for drug efficacy. The remaining were not evaluated because of dropout or exclusion. The efficacy rate combining both "Excellent" and "Good" cases, was 100% for 40 cases in which pathogens were identified, classified as Group A. The efficacy rate was 97.5% for the remaining 79 cases, classified as Group B, where causative pathogens were unidentified. The difference between the two groups was no statistical significance. The combined efficacy rate was 98.3%. For the 31 cases where the patients had failed to respond to the previous chemotherapies instituted for 3 days or longer, the efficacy rate for AZM was 93.5%. 3. Adverse reactions and abnormal laboratory tests: 8 incidents of diarrhea, skin rashes, urticaria, or vomiting were found in 7 patients (5.4%) of 130 cases eligible for evaluation. These reactions, however, were all transient and mild to moderate in severity in the 7 patients including 2 patients for whom the treatment was discontinued, all resolved in time. Abnormal changes in laboratory tests were found as follows: decrease in WBC in 10 patients (9.3%), an increase in eosinophils in 12 (11.4%), an increase in platelet count in 1 (1.0%), an elevation of GOT in 3 (3.1%), an elevation of GPT in 6 (6.2%), and an elevation of LDH in 1 (1.1%). The abnormalities were transient and did not require particular intervention. Moreover, none of the patients indicated clinical signs associated with the abnormal changes of laboratory tests.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption↗
PubMed1995

[Fundamental and clinical studies of SY5555 in pediatrics].

We assessed the in vitro antimicrobial activity and the clinical efficacy and safety of SY5555 in the field of pediatrics. The results obtained are summarized below. 1. In vitro antibacterial activities of SY5555 against 52 clinical isolates were compared with those of clavulanic acid/amoxicillin (CVA/AMPC), cefotiam (CTM), cefpodoxime (CPDX), cefaclor (CCL) and cefdinir (CFDN). Against Gram-positive bacteria, including Staphylococcus aureus, Streptococcus pneumoniae and Streptococcus pyogenes, SY5555 displayed antimicrobial activities superior or nearly equivalent to those of the reference agents used in the study. In cases of Gram-negative bacteria, the antimicrobial activity of SY5555 against Haemophilus influenzae was inferior to those of CPDX and CFDN. Against Klebsiella pneumoniae, the antimicrobial activity of SY5555 was less potent than that of CPDX. 2. Forty-seven children with infectious diseases were treated with SY5555 dry syrup (powder dissolved just before use). The clinical results were excellent in 24 and good in 16, with an efficacy rate of 85.1%. 3. Bacteriological screening identified 30 pathogenic organisms, and the eradication rate was 76.7%. 4. Side effects consisted of diarrhea in 12.5% (6 cases), loose stools in 4.2% (2 cases) and urticaria in 2.1% (1 case) of the patients. The only abnormal laboratory test value observed was an increase in eosinophil count in one child. 5. The palatability of SY5555 dry syrup was very good; it was very easily ingestable or easily ingestable by 32 of the 48 children. From the above results, SY5555 dry syrup appears to be a useful drug with a preferable safety profile in the treatment of pediatric patients with infectious diseases.

Administration, Oral↗
PubMed1995

New aerodynamic aspects of nasal patency.

In considering possible aerodynamic indicators of subjective nasal stuffiness, we measured nasal resistance, acceleration change of nasal airflow, and alteration of differential pressure and compared those with the degree of severity of sensation of nasal obstruction in 75 patients. The acceleration change of airflow and alteration of differential pressure are presented as an equation: y = ax2 + bx + c, in which "a" represents the approximate shape of the curve. Nasal resistance, on either inspiration or expiration, and coefficient "a" of acceleration change the rapid phase from inspiration to expiration correlated well with subjective nasal patency, while coefficient "a" of acceleration change the rapid phase from expiration to inspiration and alteration of differential pressure either the rapid phase from inspiration to expiration or from expiration to inspiration did not correlate well with perception of nasal blockage. It seems that measurement of respiratory acceleration of airflow of quiet nasal breathing is a useful indicator of subjective nasal patency.

Acceleration↗
PubMed1994

Thiol-mediated redox regulation of lymphocyte proliferation. Possible involvement of adult T cell leukemia-derived factor and glutathione in transferrin receptor expression.

The proliferative response of PBMC to PHA, Con A, OKT3 mAb and IL-2-dependent proliferation of PHA-blasts was examined in a thiol-free environment (cultured in a L-cystine- and GSH-free medium). [3H]TdR incorporation assay and cell cycle analysis revealed that stimulated PBMC could not enter the S phase when deprived of these thiol compounds. In thiol-free cultures, an increase in intracellular free Ca2+ concentration and IL-2R alpha-chain/p 55 (Tac) induction was still observed, whereas transferrin receptor induction was markedly reduced, suggesting that the proliferative response of mitogenically stimulated PBMC was arrested in the late G1 phase in which transferrin receptor is induced. In GSH-depleted cultures, a similar reduction of the proliferative response of PBMC and PHA-blasts was observed when the concentration of L-cystine was lowered, in a dose-dependent manner. Each reduction or loss of proliferative response was partially restored by supplementation of 2-ME or adult T cell leukemia-derived factor (ADF)/human thioredoxin which is considered to be an endogenous dithiol-reducing factor. L-Cystine transport analysis showed that mitogenically stimulated PBMC and PHA blasts incorporated L-cystine, whereas resting PBMC did not. Furthermore, ADF as well as 2-ME exhibited an enhancing activity on the L-cystine transport in PHA blasts. Together with the fact that L-cystine transport is a limiting step in glutathione synthesis, these findings suggest that GSH and ADF might cooperate in the thiol-mediated redox regulation process and might also play key roles in cell cycle (late G1 to S) progression of activated lymphocytes.

Amino Acid Sequence↗
PubMed1994

A regular 1:1 complex of two allosteric states in the single crystal of L-lactate dehydrogenase from Bifidobacterium longum.

Single crystals of the regular 1:1 complex of T and R-state tetramers of L-lactate dehydrogenase from Bifidobacterium longum have been grown from polyethylene glycol 6000 solution in the presence of NADH, fructose 1,6-bisphosphate and oxamate. The crystals belong to space group F222 with unit cell dimensions of a = 148.4 A, b = 295.9 A and c = 71.0 A. The crystals are suitable for X-ray analysis and diffract to beyond 2.5 A spacing. A crystallographic study showed that the asymmetric unit contains two subunits and that one of them belongs to the T-state tetramer and the other to the R-state tetramer.

Allosteric Site↗
PubMed1994

NADPH-cytochrome c reductase from human neutrophil membranes: purification, characterization and localization.

Neutrophil-membrane-associated NADPH-cytochrome c reductase and cytochrome b558 were separately eluted and highly purified by a combination of ion-exchange Sepharose, N-amino-octylagarose, 2',5'-ADP-Sepharose and heparin-Sepharose column chromatographies. The purified cytochrome c reductase with an apparent molecular mass of 68 kDa contained FMN and FAD (FMN/FAD approx. 1). Cytochrome b558 prepared in the presence of phospholipids and FAD showed marked O2-.-producing activity (Vmax., 8.53 mumol of O2-./min per mg of cytochrome; Km for NADPH 58.8 microM) in a cell-free assay system consisting of cytosol, arachidonate and GTP[S]. However, when it was obtained without FAD added to the purification process, it had negligible FAD and little or no O2-.-forming activity in the reconstituted system. The NADPH oxidase activity was not markedly stimulated on incubation of the purified reductase with either flavinated or flavin-depleted cytochrome b558 in the cell-free system, suggesting that the reductase is not likely to be involved in neutrophil O2-. generation. The purified reductase cross-reacted with polyclonal antibodies against both hepatic NADPH-cytochrome P-450 reductase and a synthetic peptide, ILVGPGTGIAPFRSF, which indicates residues 529-543 located in the glycine-rich NADPH-binding domain of the P-450 reductase, but cytochrome b558 did not produce any immunoreactive bands to these antibodies. These antibodies also produced a positive reaction with a 76 kDa protein from dimethyl sulphoxide-induced HL-60-cell microsomes. After solubilization of the microsomal membranes, the 76 kDa protein was readily converted into a partially proteolysed form (68 kDa) even in the presence of antiproteases. In addition, the microsomal fraction shows a CO difference spectrum with a peak at about 454 nm and a trough at 476 nm in the presence of dithionite, indicating the presence of a cytochrome P-450-like haemoprotein.

Amino Acid Sequence↗
PubMed1994

Biochemical and biophysical alterations of lipoprotein after liver transplantation from a living related donor. A biochemical and proton NMR study.

Changes in lipoprotein metabolism after liver transplantation from living related donors were investigated in nine pediatric patients by means of biochemical and proton nuclear magnetic resonance (NMR) analyses of lipoprotein. NMR offers rapid and nondestructive measurement of lipoprotein. The ratio of esterified cholesterol to total cholesterol, expected to be a prognostic indicator after liver transplantation, was low before the operation (0.44) and recovered to over 0.6 at 3 weeks. The half line width of the methylene peak of lipoprotein, as measured by proton NMR, was correlated with the ratio of esterified cholesterol to total cholesterol. It is suggested that proton NMR analysis can provide information about the biophysical changes in lipoprotein associated with liver transplantation.

Biochemical Phenomena↗
PubMed1994

Adult T cell leukemia-derived factor/human thioredoxin protects endothelial F-2 cell injury caused by activated neutrophils or hydrogen peroxide.

Adult T cell leukemia-derived factor (ADF), originally defined as an interleukin 2 receptor/alpha (alpha) chain inducer produced by human T-lymphotropic virus type-I transformed cells, is identical to human thioredoxin (TRX). In this study, the protective effect of ADF/TRX on the cytotoxicity of endothelial cells caused by phorbol myristate acetate (PMA)-activated neutrophils or hydrogen peroxide (H2O2) was examined. When murine endothelial F-2 cells established from an ultraviolet light-induced tumor on a nude mouse were incubated with PMA-activated neutrophils or with 1 mM H2O2 for 6 hours, the cytotoxicity of F-2 cells was respectively 51 +/- 4% or 40 +/- 8% by the 51Cr releasing assay. Recombinant ADF/TRX (rADF/TRX) inhibited this cytotoxicity in a dose-dependent manner, although mutant ADF/TRX (cysteine 31 to serine), 2-mercaptoethanol and dithiothreitol did not. On a molar basis, rADF/TRX was more effective than glutathione but less effective than catalase. Immunoblotting analysis showed that treatment with 0.1 mM H2O2 induced murine TRX on F-2 cells. These findings indicate that ADF/TRX is an oxidative stress-inducible endogenous protein and rADF/TRX plays a protective role against activated neutrophils- or H2O2-induced endothelial cytotoxicity.

Animals↗
PubMed1994

Ethanol stimulates chemiluminescence from neutrophils in the liver.

The production of free radicals in tissues can be continually monitored by measurement of low-level chemiluminescence. In these experiments the effects of ethanol on luminol (1 microM)-enhanced chemiluminescence were recorded in isolated perfused livers from control rats, and from rats that had undergone a 30-min period of ischemia, followed by 3 h of reinstitution of blood flow. Our previous experiments showed considerable neutrophil accumulation at this time. A routine concentration of 100 mM ethanol added after 20 min of perfusion with Krebs-Henseleit solution caused an increase in chemiluminescence of about 2000 cpm above the resting level (1600 cpm) in both control livers and livers from rats after 3 h of ischemia reperfusion in vivo. However, if ethanol was added to the perfusing medium of the isolated liver after at least 1 h of in vitro perfusion, then the magnitude of the response was very much greater (peak approximately 27000 cpm) in livers that had undergone ischemia reperfusion than in control livers (peak approximately 7000 cpm). Experiments combining addition of ethanol and the potent neutrophil stimulator, phorbol myristate acetate (PMA), plus the use of rat antineutrophil serum have shown conclusively that the very large chemiluminescent response to ethanol after prolonged in vitro perfusion is due to stimulation of neutrophil radical production.

Animals↗
PubMed1994

Seasonal variations of nasal resistance in allergic rhinitis and environmental pollen counts. III: Efficacy of antiallergic agents.

We previously reported that, in a patient with Japanese cedar pollinosis, preseasonal increase in total nasal airway resistance (NAR) possibly caused from circannual endogenous rhythm was suppressed by preseasonal systemic administration of antiallergic agent. In this study, in order to determine the influence of preseasonal use of a topical antiallergic agent and seasonal administration of a peroral antiallergic agent, we made measurement of nasal airway resistance and pollen counts under the previous respective conditions in separated years. Preseasonal high mean values of total NAR for a couple of weeks was not suppressed by the preseasonal topical administration of ketotifen nasal spray in 1992 which was a low pollen season (974/cm2). However, the patient did not complained of severe episodes of hay fever at all throughout the season. Preseasonal increases in mean values of total NAR were observed in 1993 which was a high Japanese cedar pollen season (4,875/cm2) with NAR the same as untreated seasons. This may have been because the patient was not treated with preseasonal use of peroral azelastine. On extremely high Japanese cedar pollen count days further increased NAR occurred in the patient. The patient experienced relatively severe hay fever episodes, but used no other anti-histamine nor topical steroid during the season.

Administration, Topical↗
PubMed1994

T and R states in the crystals of bacterial L-lactate dehydrogenase reveal the mechanism for allosteric control.

The crystal structure of L-lactate dehydrogenase from Bifidobacterium longum, determined to 2.5 A resolution, contains a regular 1:1 complex of T- and R-state tetramers. A comparison of these two structures within the same crystal lattice and kinetical characterization of the T-R transition in solution provide an explanation for the molecular mechanism of allosteric activation. Substrate affinity is controlled by helix sliding between subunits which is triggered by the binding of the activator, fructose 1,6-bisphosphate. The proposed mechanism can explain activation by chemical modification and mutagenesis, as well as suggesting why vertebrate counterparts are not allosteric.

Allosteric Regulation↗