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Biomedical subjects

K Chiba

Publications and source records attributed to K Chiba.

At least 307 records · Page 17Linked to original sources

[Production of IL-6 and IL-1 alpha by human corneal epithelial cells].

By using enzyme-linked immunosorbent assay (ELISA), it was demonstrated that cultured human corneal epithelial cells produced interleukin-6 (IL-6) without any stimulation. As lipopolysaccharide (LPS)-stimulation did not induce further production of IL-6 and IL-1 alpha, it was suggested that IL-6 was produced naturally as in the case of IL-1 alpha production which has been previously reported by the author. Production of IL-1 alpha and IL-6 in the human corneal epithelial cells may play a role in amplifying immune responses on the ocular surface.

Adult↗

Effects of N-methylmercaptoimidazole on the disposition of MPTP and its metabolites in mice.

The effects of N-methylmercaptoimidazole, an alternative substrate for flavin-containing monooxygenase, on the disposition of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and its metabolites, 1-methyl-4-phenyl-1,3-dihydropyridine (MPDP+) and 1-methyl-4-phenylpyridine (MPP+) in plasma and in brain tissues were studied in mice. Pretreatment of mice with N-methylmercaptoimidazole caused a significant (P less than 0.01) increase in the plasma concentration of MPTP, whereas there was no significant change in the plasma concentrations of MPDP+ and MPP+. N-Methylmercaptoimidazole caused a significant (P less than 0.01) increase in the levels of MPTP, MPDP+ and MPP+ in both the striatum and cortex. The conversion rates of MPTP to MPDP+ to MPP+ in whole brain homogenates were not affected by N-methylmercaptoimidazole. These results suggest that N-methylmercaptoimidazole increases the amount of MPTP delivered from the peripheral to the central nervous system, presumably by inhibiting MPTP N-oxygenation via the hepatic microsomal flavin-containing monooxygenase. An increased level of striatal MPP+, caused by the oxidation of more MPTP by brain monoamine oxidase, appears to be the mechanism by which the neurotoxicity of MPTP is enhanced by N-methylmercaptoimidazole.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

Effects of a novel alpha 1-adrenoceptor antagonist, SGB-1534, on adrenergically induced renal vasoconstriction in dogs.

The alpha 1-adrenoceptor antagonistic effect of SGB-1534, a novel phenylpiperazine derivative, was examined in the renal vascular bed of pentobarbital-anesthetized dogs. Renal nerve stimulation (RNS, 1 ms duration, 2, 3 and 4 Hz) or intrarenal bolus injection of methoxamine (0.5, 1 and 2 micrograms/kg) or guanabenz (1, 3 and 10 micrograms/kg) produced a frequency- or dose-dependent decrease in renal blood flow (RBF). Both the RBF responses to RNS and methoxamine were inhibited dose dependently by an intrarenal infusion of SGB-1534 (1-30 ng/kg per min) or prazosin (30-300 ng/kg per min). When the equipotent inhibitory doses of the antagonists were compared, the antagonistic potency of SGB-1534 on the RBF responses evoked by RNS and methoxamine was about 30 times greater than that of prazosin. Prazosin also attenuated the RBF response to guanabenz, whereas SGB-1534 had little effect. These results suggest that SGB-1534 has a selective alpha 1-adrenoceptor-blocking property and that it inhibits neurally mediated renal vasoconstriction. The alpha 1-adrenoceptor antagonistic potency and selectivity of SGB-1534 may be greater than that of prazosin.

Adrenergic alpha-Antagonists↗

Radioimaging of human glioma xenografts with 123I labeled monoclonal antibody G-22 against glioma-associated antigen.

Monoclonal antibody (MCA) G-22 is directed against a human glioma-associated surface antigen. Its availability for the radioimmunodetection of human glioma was analyzed by utilizing the xenografts in athymic mice. Nude mice with subcutaneous grafts of U251-MG or U251-SP glioma received intravenous administration of 123I or 131I labeled F(ab')2 fragment or whole immunoglobulin. Results of radioimaging revealed that 123I-labeled antibody was better than the 131I-labeled. It was also noted that administration of 123I-labeled F(ab')2 fragment of G-22 MCA enabled the imaging of human glioma xenografts weighing 80-650 mg after 48 hours. When biodistribution of 123I MCA was compared between G-22 and control antibodies, the percentages of dose/g in tumors were 5.228-1.799 at 30 hours and 4.112-1.132 at 48 hours with G-22 and they were 4.164-1.248 and 0.314-0.142 with control. The tumor/blood ratio until 72 hours after injection was constantly above 1 with G-22 and less than 1 with control antibody. These results indicate the potential usefulness of G-22 MCA for the radioimmunodetection of human gliomas.

Animals↗

Development of calcium release mechanisms during starfish oocyte maturation.

In response to the maturation-inducing hormone 1-methyladenine, starfish oocytes acquire increased sensitivity to sperm and inositol trisphosphate (InsP3), stimuli that cause a release of calcium from intracellular stores and a rise in intracellular free calcium. In the immature oocyte, the calcium release in response to 10 sperm entries is less than that seen with a single sperm entry in the mature egg. Likewise, the sensitivity to injected InsP3 is less in the immature oocyte. Approximately 100 times as much InsP3 is required to obtain the same calcium release in an immature oocyte as in a mature egg. However, with saturating amounts of InsP3, immature oocytes and mature eggs release comparable amounts of calcium. These results indicate that although calcium stores are well-developed in the immature oocyte, mechanisms for releasing the calcium develop fully only during oocyte maturation.

Adenine↗

Interaction between lipids and bovine brain calmodulin: lysophosphatidylcholine-induced conformation change.

We have monitored the interaction of several lipids with the bovine brain calmodulin(CaM) and analyzed the effect of lysophosphatidylcholine(lyso-PC, 2-50 micrograms/ml) on conformation of CaM and the interaction between CaM and CaM-binding protein(CaMBP), using a fluorescence signal of 1-(dimethylamino)naphthalene-5-sulfonate-labeled CaM(DNS-CaM). Lyso-PC(egg, 20 micrograms/ml), among various natural lipids including phosphatidylserine(PS), phosphatidylinositol(PI), phosphatidylethanolamine (PE) and their lyso forms, greatly and dose-dependently enhanced the intensity of DNS fluorescence of DNS-CaM in the presence (100 microM CaCl2) and absence (1 mM EGTA) of Ca2+. Apparent dissociation constants calculated from the fluorometric titrations of binding of lyso-PC to DNS-CaM were 0.6 and 3.7 micrograms/ml in the presence and absence of Ca2+, respectively. Lyso-PC remarkably prevented both trypsin-induced quenching of the fluorescence of DNS-CaM and tryptic digestion of native CaM in the absence of Ca2+. Enhancement of DNS fluorescence of DNS-CaM by CaMBP was observed only in the presence of Ca2+ and lyso-PC could further increase the fluorescence intensity of the complex. These all results suggest that lyso-PC can modulate the interaction between CaM and CaMBP as a result of its direct effect on conformation of CaM.

Animals↗

Synthesis and structure-activity relationships of 5-substituted 6,8-difluoroquinolones, including sparfloxacin, a new quinolone antibacterial agent with improved potency.

A series of 5,7-disubstituted 1-cyclopropyl-6,8-difluoro-4(1H)-oxoquinoline-3-carboxylic acids (10-36) were prepared; the C-5 substituent in these compounds comprised halo, hydroxy, mercapto, and amino groups and the C-7 functional group included variously substituted piperazines. In vitro antibacterial screening results indicated that the amino group was optimal among the C-5 substituents. A combination of the C-5 amino group and the C-7 3,5-dimethylpiperazinyl appendage in this series conferred the best overall antibacterial property with lack of adverse drug interactions. Compound 36k [named sparfloxacin, originally AT-4140, 5-amino-1-cyclopropyl-6,8-difluoro-7-(cis-3,5-dimethyl-1-piperazinyl)- 4(1H)-oxoquinoline-3-carboxylic acid] was superior to ciprofloxacin in both in vitro and in vivo potency and hence was selected as a promising candidate for an improved therapeutic agent.

4-Quinolones↗

Effect of nipradilol on myocardial energy metabolism in the dog ischaemic heart.

The effect of nipradilol, a newly developed beta-adrenoceptor blocking agent with a vasodilatory action, on myocardial energy metabolism has been examined in the dog ischaemic heart, and compared with that of propranolol. Ischaemia was induced by ligating the left anterior descending coronary artery. Either saline, nipradilol (0.3 mg kg-1), or propranolol (1 mg kg-1) was injected intravenously 5 min before coronary ligation. After 3 or 30 min of coronary ligation, the ischaemic region of the myocardium was removed, and the endocardial portion used to determine the levels of adenosine triphosphate (ATP), adenosine diphosphate (ADP), adenosine monophosphate (AMP), creatine phosphate (CrP) and lactate. Ischaemia decreased the levels of ATP and CrP, and increased the levels of ADP, AMP and lactate. Immediately after the injection of nipradilol, rapid falls in blood pressure and heart rate were observed. Pretreatment with nipradilol lessened the decreases in the levels of ATP and CrP and the increases in the levels of AMP and lactate, caused by 3 min of ischaemia, to the same extent as propranolol. However, after 30 min of ischaemia, nipradilol had no effect on myocardial metabolism unlike propranolol. These results indicate that nipradilol can reduce ischaemic influences on myocardial metabolism as well as propranolol, but only in the early stages of ischaemia.

Adenine Nucleotides↗

Abnormal hepatobiliary clearance of 99mTc-N-(2,6-diethylphenylcarbamoylmethyl)iminodiacetic acid in the altered state of thyroid--by an analysis of deconvolution method.

Hepatobiliary clearance of 99mTc-EHIDA was investigated in cases with altered thyroid function by deconvolution method. The results indicated that mean hepatic transit time of all control subjects revealed less than 10 minutes. On the other hand, mean hepatic transit time of cases with altered thyroid function revealed prolonged more than 13 minutes. Cases especially showing an elevated serum concentration of TSH compared with normal range (4.6 microU/ml) had a tendency of a high incidence of markedly prolonged mean hepatic transit time. These results suggest that thyroid hormone may influence on the hepatic metabolism of hepatobiliary radiopharmaceuticals. This phenomenon also could partly explain the cause of liver dysfunction seen in subjects with altered states.

Adult↗

[Pathogenesis and pathophysiology of ischemic leukoencephalopathy].

The cerebral white matter is highly susceptible to ischemic damage because of its location in the end-fields of penetrating arteries. Our studies have shown that hypertension, short-term variability of blood pressure, decreased oxygen dissociation of hemoglobin, and increased resistance of cerebral arterioles play important roles in the pathogenesis of Binswanger type dementia. While hypoperfusion was most remarkable in the frontal area and dopamine metabolism in the cerebrospinal fluid was impaired in Binswanger type dementia, cerebral blood flow decreased most conspicuously in the parietal area and there was an impairment of noradrenaline metabolism in the cerebrospinal fluid in senile dementia of Alzheimer type. Previous anatomical studies have indicated that the ascending dopaminergic system predominantly innervates the frontal cortex, while the noradrenergic system projects all cortical areas, including the parietal cortex. Our findings suggest frontally-dominant dysfunctions in Binswanger type dementia.

Blood Pressure↗

[Paratesticular rhabdomyosarcoma: a case report].

A thirteen-year-old boy noted a swelling in his right scrotum one year prior to admission. On August 7, right high orchiectomy was performed. The tumor mass measured 10 x 6 x 7 cm. Microscopic examination revealed alveolar type rhabdomyosarcoma. Lymphangiography and computed tomography revealed retroperitoneal lymph node metastasis. He was treated with VAC therapy (vincristine, actinomycin D, cyclophosphamide) and VAD therapy (vincristine, adriamycin). This drug combination was effective, and he has been followed for two years with no evidence of recurrence.

Adolescent↗

Simultaneous determination of disopyramide and mono-N-dealkyldisopyramide enantiomers in plasma and urine by use of a chiral cellulose-derivative column.

This assay allows simultaneous determination of the enantiomers of both disopyramide and its active metabolite, mono-N-dealkyldisopyramide, in 1 mL of plasma or 0.1 mL of urine within approximately 35 min by HPLC with a chiral cellulose-derivative column and ultraviolet detection. Recoveries for the analytes and the internal standard (racemic verapamil) with an extraction from alkalinized plasma or urine into diethyl ether were greater than 90%. Intra- and interassay CVs for disopyramide enantiomers were less than 5.5% at 2.5 mg/L in plasma and less than 6.5% at 25 mg/L in urine; for mono-N-dealkyldisopyramide enantiomers they were less than 6.3% and less than 8.9%, respectively. Intra- and interassay relative errors for determining these analytes in plasma and urine at 2.5 and 25 mg/L, respectively, ranged from -5.9% to +2.5%. The calibration curves for the respective analytes were linear (r = 0.995 or greater, P less than 0.01) from 0.025 to 5.0 mg/L in plasma and from 0.5 to 10 mg/L in urine. The lower detection limits (signal-to-noise ratio of 3) for S(+)-disopyramide and the other analytes were 0.010 and 0.025 mg/L, respectively. We evaluated clinical applicability of this method by determining steady-state plasma concentrations and urinary excretions of the respective analytes in a pediatric patient being treated with racemic disopyramide.

Anti-Arrhythmia Agents↗

Effect of vinpocetine on oxygen release of hemoglobin and erythrocyte organic polyphosphate concentrations in patients with vascular dementia of the Binswanger type.

Oxygen affinity of hemoglobin, erythrocyte 2,3-diphosphoglycerate (DPG) and adenosine triphosphate (ATP) concentrations were compared before and after oral administration of vinpocetine (TCV-3B) (15 mg/d), a primarily vasodilating agent, for three weeks in eight patients with vascular dementia of the Biswanger type which is characterized by diffuse myelin pallor and multiple lacunes in the cerebral white matter. After vinpocetine administration, oxygen affinity of hemoglobin (P50) was significantly increased (26.5 +/- 0.55 to 27.6 +/- 0.62 mmHg; mean and standard deviation, p less than 0.05), red blood cell (RBC) ATP concentrations were significantly increased (846 +/- 168 to 1,158 +/- 130 mumol/l RBC, p less than 0.05), while DPG concentrations were unaltered (4.46 +/- 0.48 to 4.59 +/- 0.57 mmol/l RBC). There was a significant positive correlation between the increase of P50 and the increase of erythrocyte ATP concentrations (r = 0.67, p less than 0.05). The effect of vinpocetine of enhancing oxygen release of hemoglobin may offer an additional benefit to its primary vasodilating action in the treatment of vascular dementia of the Binswanger type due to chronic ischemia.

Adenosine Diphosphate↗

Conformation change of the intestinal calcium-binding protein induced by phospholipids in the presence and absence of Ca2+.

Effects of phospholipids (PL's) and lyso-PL's on the conformation of the porcine intestinal calcium-binding protein (CaBP) were studied fluorometrically with 1-(dimethylamino)naphthalene-5-sulfonyl-(DNS-) labeled CaBP. The fluorescence intensity of DNS-labeled CaBP was much higher in the presence of excess EGTA than in its Ca2+-bound state. In the absence of free Ca2+ (with 1 mM EGTA) the fluorescence of the labeled CaBP was greatly enhanced by addition of lysophosphatidylcholine (lyso-PC), lysophosphatidylserine (lyso-PS), or lysophosphatidylinositol (lyso-PI). With addition of 25 microM Ca2+ the enhancement of the fluorescence by these lyso-PL's was depressed; especially that due to lyso-PC became small. Lysophosphatidylethanolamine (lyso-PE), phosphatidylcholine (PC), phosphatidylserine (PS), phosphatidylinositol (PI), phosphatidylethanolamine (PE), and mono- and dipalmitoylglycerols had no or much less effect on the fluorescence in the presence and absence of Ca2+. Lyso-PC attenuated in a concentration-dependent manner the quenching of the fluorescence of the DNS-CaBP by high temperatures and increase of ionic strength in the presence of EGTA. Lyso-PL's generally protected the CaBP from digestion with proteases in the presence of EGTA. These experimental results suggest that particular lyso-PL's have Ca2+-sensitive interaction with the porcine CaBP and induce conformation change of the CaBP molecules.

Animals↗

Purification and characterization of a novel calcium-dependent serine proteinase secreted from malignant hamster embryo fibroblast Nil2C2.

A novel serine proteinase was purified from the conditioned medium of malignant hamster embryo fibroblasts, Nil2C2. The molecular weight of the purified enzyme was estimated to be 88,000 on sodium dodecyl sulfate-polyacrylamide gel electrophoresis under non-reducing conditions. The enzyme was split into two subunits (Mr 66,000 and 33,000) with a reducing agent. The enzyme hydrolyzed not only synthetic peptides which are susceptible to trypsin digestion but also extracellular matrix proteins such as type I and IV collagen, fibronectin and gelatin. For the digestion of these proteins, Ca2+ at millimolar concentrations was essential but Ca2+ or chelators did not affect the esterase activity for synthetic peptides. The proteolytic activity was inhibited by diisopropyl fluorophosphate (DFP) and also by phenylmethylsulfonyl fluoride. DFP was shown to bind to the 33 kDa subunit, indicating that the catalytic machinery of the enzyme is located in this subunit.

Animals↗

Interleukin-1-like activity in the exudate of air-pouch inflammation in rats, and its participation in granuloma formation.

The in vivo production of lymphocyte activating factor (LAF) activity was investigated in the exudate of the rat air-pouch inflammation model. An inflammatory reaction was induced by lipopolysaccharide (LPS) injection into the air-pouch, and the time course of LAF activity in the exudate was investigated. LAF activity in the exudate reached a peak by 6 h, and rapidly decreased at 10 to 48 h after the LPS injection. Dexamethasone revealed strong inhibitory action on LAF activity and granuloma formation. On the other hand, indomethacin could not inhibit either of the phenomena. In conclusion, LAF (IL-1) is rapidly produced after the onset of inflammation and may participate in the subsequent granuloma formation.

Animals↗

Pertussis toxin inhibits 1-methyladenine-induced maturation in starfish oocytes.

Starfish oocytes injected with pertussis toxin (3-6 micrograms/ml) or its catalytically active A-subunit (1 microgram/ml) did not undergo germinal vesicle breakdown in response to 1-methyladenine (1-10 microM). The pertussis block could be bypassed by transfer of cytoplasm that contained maturation-promoting factor (MPF). After insemination, pertussis-blocked, MPF-rescued oocytes underwent cortical vesicle exocytosis and cleavage. These results suggest the involvement of a pertussis sensitive G-protein in the pathway coupling 1-methyladenine action at the cell surface to the reinitiation of meiosis.

Adenine↗

The addition of an adhesive composite resin to the same material: bond strength and clinical techniques.

The addition of a chemically adhesive composite resin to a restoration of the same material may be evaluated by the bond strength. This was determined after no contamination and after momentary (30 seconds), short-term (7 days), and long-term (3 months) contamination under various conditions. The momentary contamination was not removed by spray-washing the glossy surface that set under a matrix. Removing the glossy surface reduced the bond. The momentary contamination was removed by the etchant whereas the longer contamination was removed only by surface reduction. The application of etchant and bonding agents significantly strengthened the bond to the reduced surface. According to the directives drawn from this investigation, the clinical techniques were illustrated for a large restoration, a subgingival proximal restoration, repair of an open proximal contact, and repair of a worn restoration.

Composite Resins↗