Biomedical subjects
Publications and source records attributed to M Nakano.
1. Cytochrome P-450-linked monooxygenase of mitochondria and microsomes of the cerebrum, cerebellum and pituitary gland of bovine brain were investigated biochemically and immunochemically. 2. The cytochromes P-450scc and P-450(11) beta, NADPH-ferredoxin reductase and adreno-ferredoxin were detected and their enzymatic activities of steroid hydroxylations were found in the bovine brain.
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In order to examine the functional changes in the vascular smooth muscle, the effects of a thromboxane A2 synthetase inhibitor (OKY-046) and a calcium channel blocker (diltiazem) on vessels following subarachnoid hemorrhage, and the contractile activity of cerebral vessels with various vasoactive agents, were investigated by studying isometric tension recordings in rings of cat basilar artery. The maximum contractile activities of the vessels in response to noradrenalin and adrenaline during the course of subarachnoid hemorrhage were significantly less than those in the control group. On the other hand, the maximum contractile activity of the vessels in response to prostaglandin F2 alpha on the seventh day following subarachnoid hemorrhage was significantly augmented compared with that in the control group. A significant decline in the relaxation of responsiveness to diltiazem during the course of subarachnoid hemorrhage was observed compared with that of diltiazem in the control group. This responsiveness to vasoactive agents was not influenced by the application of OKY-046. The present study reveals functional changes in vascular smooth muscle exposed to subarachnoid hemorrhage in response to vasoactive agents and a calcium entry blocker. Thromboxane A2 may not be a significantly influential factor in the present results. It is suggested that cerebral vasospasm may well be related to functional changes of the arterial wall, which appear to be associated with derangement of the mechanisms of smooth muscle constriction and dilatation based on organic changes.
The ability of recombinant murine (rMu) interferon (IFN)-gamma to activate anti-Salmonella-activity in normal mice and beige mutant (bg/bg) mice with Chediak-Higashi syndrome (CHS) was examined. Previous intraperitoneal (i.p.) injection of rMuIFN-gamma (10(4) U per mouse) significantly hindered the bacterial growth in the peritoneal cavities, spleens and livers of the mice after the i.p. infection with Salmonella enteritidis No. 11 strain. It was also effective on the beige mice that have phagocytic cells with a genetically impaired bactericidal function, suggesting that IFN-gamma activates the pathway irrelevant to the beige mutation. The effect was the maximum, when IFN-gamma was given 6 h before the challenge. The effect seemed to be due to the augmentation of bactericidal capacity rather than the prevention of systemic spread of bacteria. Recombinant human IFN-alphaA/D (10(2)-10(6) U per mouse), which produced effects identical to those of murine IFN-beta, did not show such a bactericidal effect. Bactericidal activity enhancement was also seen in mice that had been injected with a small amount of rMuIFN-gamma (10(2) U) and bacterial lipopolysaccharide (LPS) (10 ng) together at 6 h before the challenge, although the IFN-gamma or LPS alone at these doses produced very little if any effect. Bactericidal effect enhancement was seen in mice that had been injected with IFN-gamma at 6 h and LPS at 3 h before the challenge, while it could be hardly seen in mice injected with them in a reversed order.(ABSTRACT TRUNCATED AT 250 WORDS)
Fc gamma receptor (Fc gamma R)-dependent immunoregulation by murine heat-aggregated (HAgg) IgG subclasses on the bacterial lipopolysaccharide (LPS)-induced plaque forming cell (PFC) response to trinitrophenylated sheep red blood cell (TNP-SRBC) antigen and the competitive effect by Fc gamma 2bR-protein on the down regulation by HAgg-IgG2b were studied in murine T-cell-deprived spleen cell cultures. HAgg-IgG1 and HAgg-IgG3 enhanced the PFC response, but HAgg-IgG2b strongly suppressed the LPS-induced PFC response. HAgg-IgG1 could not compete with the suppressive effect of HAgg-IgG2b. The HAgg-IgG2b seemed to act on both macrophages (M phi) and B-cells, because the cell cultures that had been reconstituted with HAgg-IgG2b-pretreated M phi and untreated B-cells and vice versa showed poor PFC responses. The suppression induced by HAgg-IgG2b on the LPS-induced PFC response in the T-cell-deprived cultures was abolished by the addition of phospholipase C (PLC)-treated Fc gamma 2bR protein at the early stage of the culture. The mechanisms by which HAgg-IgG2b suppress the LPS-induced PFC response and PLC-treated Fc gamma 2bR protein restores this response were discussed.
Biliary atresia patients have several problems even after undergoing successful Kasai operation. Fourteen female patients have been followed for over 12 years after successful Kasai original portoenterostomy procedures. The oldest patient is 21 years of age. All patients are jaundice-free, but 10 patients have a history of esophageal varices and/or hypersplenism. Five patients complain of menstrual disorders. The average age of menarche was delayed 1 year, 9 months, compared with Japanese controls. Two cases of 11 (18.2%) presented primary amenorrhea after 14 years, 6 months, which is mean + 2SD of Japanese controls. Four cases of 11 (36.4%) showed secondary amenorrhea. Unestablished menstrual cycles after 2 years of menarche were observed in two patients of nine (22.2%). Four cases had regular menstruation. Five patients showed delay in the development of pubic hair and breasts. Six patients showed atypical body height velocity pattern that showed no peaking, and one patient showed no growth spurt. All the patients with amenorrhea had portal hypertension. In hormonal evaluation, the patients with menstruation showed normal or slightly good reaction of luteinizing hormone and follicle stimulating hormone in the luteinizing hormone-releasing hormone test, having normal to high estradiol levels. The patients with menstrual abnormality showed overreaction of LH, having normal estradiol levels.
We treated 34 patients with staghorn calculi by fiberoptic transurethral nephrolithotripsy with a flexible nephroureteroscope and an electrohydraulic lithotriptor. Of the 34 patients 30 (88.2%) were treated successfully. There were 17 patients each with complete and partial staghorn calculi. There was no difference in the success ratio and the rate of residual fragments between the 2 groups. However, post-procedural fever, sepsis and extrapelvic extravasation were observed more frequently in patients with complete than with partial staghorn calculi. Countermeasures to avoid complications must be developed in the future. However, we believe that fiberoptic transurethral nephrolithotripsy is a safe and effective treatment for staghorn calculi. This procedure also should be recommended, as well as the combination of percutaneous nephrolithotomy and extracorporeal shock wave lithotripsy.
The glycoproteins of porcine zonae pellucidae have been fractionated into three families (PZP1-3) by gel filtration HPLC [Nakano et al. (1987) Biochem. Int. 14, 417-423]. However, they still comprise heterogeneous molecular species differing in electric charge. We found that sulfate, but not phosphate, is contained in PZP1-3 by a simple and rapid method for microanalysis of the anionic groups. These families were efficiently separated into many fractions by anion-exchange HPLC. When elution was performed by stepwise increase in NaCl concentration in 8 M urea/20 mM Tris-HCl, pH 8.0, a single distinctive peak emerged for each step. The analyses of amino acids, monosaccharides, and anions of the eight separated fractions of the major family, PZP3, showed that larger amounts of sulfated lactosamine linked to the constituent proteins are present in the fractions that are eluted later: the chain length and/or the chain number of these polylactosamines and the sulfate content increased with stepwise increase in NaCl concentration. Composition analyses also revealed that twice as much N-glycolylneuraminic acid is present as N-acetylneuraminic acid in all fractions. The contents of these sialic acids in the fractions slightly increased in the order of elution. These results together with those of the analyses of endo-beta-galactosidase digests showed that the charge heterogeneity of the porcine zona proteins is due mainly to differences in the amount of sulfated lactosamine, which is predominantly distributed in the non-reducing regions of the sugar chains.
1. The effect of kappa (kappa) opioid receptor activation on the increase in arginine vasopressin (AVP) secretion evoked by two acute and quite different stimuli (i.e., haemorrhage and osmotic stimulus due to hypertonic saline infusion) were evaluated in conscious Long-Evans rats, by use of U-62066E, a highly selective kappa-opioid receptor agonist, and MR2266, an opioid receptor antagonist with some selectivity for kappa-receptors. 2. An acute haemorrhage, which reduced the mean blood pressure by approximately 50%, resulted in a large increase in the plasma AVP (pAVP) levels of control rats. However, the administration of U-62066E (0.2 mg kg-1 or 2.0 mg kg-1) reduced the increase due to haemorrhage in a dose-dependent manner. In contrast, concomitant administration of 2.0 mg kg-1 of MR2266 with U-62066E significantly attenuated the inhibition of pAVP levels produced by U-62066E 2.0 mg kg-1. 3. Hypertonic saline infusion (5% hypertonic saline solution at a rate of 0.24 ml kg-1 min-1 for 10 min) caused the elevation of plasma osmolality (pOsm) from 294.0 +/- 1.6 mosmol kg-1 to 304.4 +/- 1.9 mosmol kg-1, simultaneously resulting in a significant increase in pAVP levels from 2.34 +/- 0.28 pg ml-1 to 4.54 +/- 0.51 pg ml-1. However, the administration of U-62066E (0.05 mg kg-1 or 0.2 mg kg-1) reduced the osmotically induced increase in pAVP in a dose-dependent manner although pOsm showed the same degree of increase as in controls. In contrast, concomitant administration of 0.2mgkg-1 of MR2266 with U-62066E significantly attenuated the inhibition of pAVP levels produced by U-62066E 0.2mgkg- , whereas pOsm showed the same degree of increase as in controls. No significant changes in the mean blood pressure of the respective groups were observed during this experiment. 4. It is suggested that the Kappa-Opioid receptor activation reduces the increase in AVP secretion evoked by these two different stimuli and that the inhibitory involvement occurs in the neural lobe in the process of AVP secretion.
Intestinal dialysis of drugs by oral administration of activated charcoal has been compared with peritoneal dialysis in rats. The average amounts of theophylline transported over 120 min into the intestinal lumen and the peritoneal cavity were 15.7 and 16.5% of the intravenous dose (10 mg kg-1), respectively, showing no significant difference, whereas the amount of the same intravenous dose of phenobarbitone transported from the blood into the intestinal lumen (7.8%) was significantly smaller than that entering the peritoneal cavity (12.5%). The net water flux showed that secretion predominated in the peritoneal transport whilst absorption predominated in the intestinal transport for both drugs. However, the net water flux in the intestinal lumen after intravenous theophylline (as aminophylline) was significantly smaller than that following phenobarbitone. The differences in transport across the two membranes could be due to differences in the intrinsic properties of the could be due to differences in the intrinsic properties of the membranes, such as the surface area, the thickness of the membrane and the distribution of blood vessels. Differences could also be due to differences in the pharmacological effects of the drugs.
The ability of granulocytes to generate superoxide anions (O2-) and hypochlorite (OCl-) during phagocytosis was investigated using peripheral blood samples from adults and cord blood samples from neonates, using the chemiluminescence probe cypiridina luciferin analog (CLA) for O2- generation and luminol (L) for OCl- generation. OCl- generation by granulocytes was also monitored by taurine chloramine formation. The chemiluminescence probe based upon CLA was highly specific for and sensitive to O2- and could be adopted to determine O2- generation in terms of xanthine oxidase units. The CLA-dependent chemiluminescence by cord blood granulocytes was significantly higher than that by normal adult granulocytes. Taurine chloramine formation was significantly correlated with the L-dependent chemiluminescence (L-CL). Thus, the L-CL is considered to be mainly involved in OCl- generated by phagocytizing granulocytes. L-CLs by cord blood granulocytes and normal adult granulocytes were essentially the same during phagocytosis.
Effects of H1-receptor stimulation on coronary arterial diameter and coronary hemodynamics were examined in 11 patients with angiographically normal coronary arteries and without variant angina or resting angina. Selective H1-receptor stimulation was achieved by infusing histamine into the left coronary artery at a rate of 2.0 micrograms/min for 5 minutes after pretreatment with cimetidine (25 mg/kg). Plasma histamine concentration in the coronary sinus, coronary sinus blood flow, heart rate, and aortic pressure were measured before, during, and after the histamine infusion. Coronary arterial diameter was measured by cinevideodensitometric analysis of coronary arteriograms performed before and immediately after the histamine infusion. During the histamine infusion, plasma histamine concentration in the coronary sinus increased from 0.33 +/- 0.06 to 5.86 +/- 0.71 ng/ml (p less than 0.01); coronary sinus blood flow increased from 98 +/- 12 to 124 +/- 13 ml/min (p less than 0.01), and coronary vascular resistance decreased from 1,113 +/- 117 to 851 +/- 91 mm Hg.min/l (p less than 0.01). Heart rate and aortic pressure remained unchanged. The mean luminal diameters of the proximal, middle, and distal left anterior descending artery increased by 9.4 +/- 3.6% (p less than 0.05), 19.2 +/- 3.8% (p less than 0.001), and 31.5 +/- 5.6% (p less than 0.001), respectively, after the histamine infusion. The mean luminal diameters of the proximal, middle, and distal left circumflex artery increased by 15.2 +/- 3.6% (p less than 0.01), 17.5 +/- 5.2% (p less than 0.01), and 20.6 +/- 4.3% (p less than 0.001), respectively, after the histamine infusion.(ABSTRACT TRUNCATED AT 250 WORDS)
The effect of a new polystyrene-based, strongly basic, anion-exchange resin possessing an omega-oxobutyl chain as a spacer arm on the fecal bile acid excretion was investigated in rats and compared with that of Dowex 1-X2, chemically equivalent to cholestyramine. The new resin did produce a significant rise in the total fecal bile acid excretion with its ingestion for a period of 4 weeks. Its promoting activity proved to be 2.0- and 1.8-fold more potent than that of Dowex 1-X2 at the 3rd and 4th week, respectively. These results suggest that the introduction of a spacer arm between the polymer backbone and a functional group would lead to an improvement in the in vivo adsorptive efficiency of the resin.
The effect of food on the rate and extent of bioavailability of bromazepam was examined in seven normal volunteers following a single oral dose of 10 mg bromazepam with 200 ml of water in the fasting and non-fasting states. Plasma concentrations of bromazepam were measured by high pressure liquid chromatography. A tmax value in a non-fasting state was prolonged from 2.3 +/- 0.3 (mean +/- S.E.M.) to 2.8 +/- 0.6 h but not significantly different (p greater than 0.05) whereas a Cmax value was significantly (p less than 0.05) decreased from 259 +/- 12.7 (mean +/- S.E.M.) to 169 +/- 13.9 ng/ml. The area under the plasma concentration-time curve in the non-fasting state was also significantly (p less than 0.05) decreased from 1844 +/- 145 (mean +/- S.E.M.) to 1233 +/- 98.1 ng.h/ml after oral administration of bromazepam.
The in vitro adsorption characteristics of activated carbon beads suitable for oral administration and the original fine powder were examined, using phenobarbital as the test drug. The extent and rate of drug adsorption on carbon in the beads were almost equal to those on the powder. In three healthy volunteers, 10 g of activated carbon beads administered orally 20 min after 120 mg of phenobarbital, reduced the total bioavailability by 57% (p less than 0.005), based on the salivary AUC-value during 96 h and the achieved peak concentration of the drug in salvia by 51%. These results demonstrated the potency of activated carbon beads as a gastrointestinal adsorbent in acute intoxications from phenobarbital.
The cytotoxicity of gamma-linolenic acid (C18:3n-6) against rat hepatoma AH-109A cells and the effect of bovine serum albumin (BSA) on its toxicity were examined in culture. The proliferation of AH-109A cells, evaluated by the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay, was significantly suppressed by gamma-linolenic acid above 5 micrograms/ml concentration in serum-free culture medium. However, its toxicity was reduced by supplement of BSA. Similar observation of reduced toxicity by BSA was shown by the method of trypan blue dye exclusion and a colony formation assay. The cytotoxicity of gamma-linolenic acid was correlated closely with the concentration of unbound (free) gamma-linolenic acid. Production of thiobarbituric acid reactive material, one of the indicators of lipid peroxidation, was stimulated by gamma-linolenic acid and inhibited by BSA. These results suggested that the presence of albumin suppressed the cytotoxicity of the free fatty acid.