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Biomedical subjects

N Ono

Publications and source records attributed to N Ono.

At least 55 records · Page 3Linked to original sources
PubMed1999

Multiple lymphomatous polyposis of the gastrointestinal tract is a heterogenous group that includes mantle cell lymphoma and follicular lymphoma: analysis of somatic mutation of immunoglobulin heavy chain gene variable region.

Multiple lymphomatous polyposis (MLP) is characterized by multiple polyps involving long segments of the gastrointestinal (GI) tract. MLP is thought to represent mantle cell lymphoma (MCL) of the GI tract; however, some cases of follicular lymphoma (FL) of the GI tract are found with a multiple polypoid appearance. In the present study, to clarify the cellular origin of MLP, clonal immunoglobulin heavy chain (IgH) gene rearrangement of four cases with MLP was amplified by polymerase chain reaction (PCR) and analyzed for the presence of somatic mutation. The IgH variable (VH) region sequences of three cases (CD5+ CD10- cyclin D1+) showed a little somatic mutation compared with the closest published germline. The other case (CD10+ CD5- cyclin D1-) was highly mutated and showed intraclonal heterogeneity (ongoing somatic hypermutation). These data indicate that three of the cases with MLP are derived from pregerminal center B cells (mantle zone B cells) and one case with MLP from germinal center B cells. Our study suggests that MLP is a heterogenous group that includes MCL and FL.

Adult↗
PubMed1999

Evaluation of anti-herpesvirus activity of (1'S,2'R)-9-[[1',2'-bis(hydroxymethyl)cycloprop-1'-yl]methyl]- guanine (A-5021) in mice.

The anti-herpesvirus activity of (1'S,2'R)-9-[[1',2'-bis(hydroxymethyl)cycloprop-1'-yl]methyl]guani ne (A-5021) was evaluated in murine cells and in several murine models of herpes simplex virus (HSV) infection. Against HSV type 1 (HSV-1), A-5021 was 15-30- and 30-60-fold more active, and against HSV type 2 (HSV-2), it was 2- and 8-fold more active than acyclovir and penciclovir in Balb/3T3 cells, respectively. When antiviral compounds were administered orally (once daily) to mice infected intraperitoneally with HSV-1 (Tomioka), A-5021 was more active than acyclovir or famciclovir in spite of its relatively low oral bioavailability. A-5021 was as active as penciclovir when the antiviral compounds were given intravenously (three times daily) to mice infected intraperitoneally with HSV-2 (186). In mice with a cutaneous HSV-1 (KOS) infection, three times daily oral therapy with A-5021 at 25 mg/kg per day produced more significant reduction in severity of skin lesions than equivalent treatment with acyclovir or famciclovir. In mice infected intracerebrally with HSV-1 (Tomioka), complete survival was observed in the group treated intravenously with A-5021 at 25 mg/kg per day (three times daily), while more than 50% of mice died in the groups treated intravenously with acyclovir of up to 100 mg/kg per day (three times daily). Moreover, A-5021 was more effective than acyclovir in clearing infectious virus from the brain. These findings demonstrate that A-5021 has potent anti-HSV activity in several murine models.

3T3 Cells↗
PubMed1999

Effect of transcatheter arterial chemoembolization on kidney hemodynamics and function in patients with cirrhosis and hepatocellular carcinoma.

BACKGROUND/AIMS: Transcatheter arterial chemoembolization (TACE) may have deleterious effect on the kidney in patients with cirrhosis and hepatocellular carcinoma. The aim of the study was to test this hypothesis. METHODS: Twenty-four patients with cirrhosis and hepatocellular carcinomas were included. They consisted of 16 patients undergoing a single TACE and eight patients undergoing diagnostic angiography. Doppler ultrasonography was used to measure hepatic artery pulsatility index (HA-PI) and renal artery pulsatility index (RA-PI) before and 1 day and 10 days after the procedure. Similarly, kidney function was assessed by measuring creatinine clearance. In addition, plasma renin activity, noradrenaline, and endothelin-1 were also measured. RESULTS: In patients receiving diagnostic angiography, no significant changes in HA-PI were observed after the procedure. In contrast, HA-PI increased significantly 1 day after the procedure (19%, p<0.01) in patients undergoing TACE, although it returned to baseline value 10 days after the procedure. In patients undergoing diagnostic angiography, no significant changes in RA-PI were observed after the procedure. Similarly, no detectable changes in RA-PI were noted in patients undergoing TACE. A transient small reduction in creatinine clearance was noted after the procedure in patients undergoing diagnostic angiography (-12%, p<0.05) and in those undergoing TACE (-11%, p<0.05). However, the effect was similar in the two groups (two-way ANOVA, p=0.72). No significant changes in plasma renin activity, noradrenaline, and endothelin-1 were observed after either diagnostic angiography or TACE. CONCLUSIONS: These results suggest that TACE per se has no deleterious effect on the kidney hemodynamics and function in patients with cirrhosis and hepatocellular carcinoma.

Aged↗
PubMed1999

Determination of stability constant of beta-cyclodextrin complexes using the membrane permeation technique and the permeation behavior of drug-competing agent-beta-cyclodextrin ternary systems.

The stability constants (Kc) of beta-cyclodextrin (beta-CyD) complexes with phenacetin and various benzoic acids were determined using the membrane permeation technique using a cellophane membrane permeable for guest molecules which was impermeable for beta-CyD molecules. The permeation rate equations of guests in the presence of beta-CyD in the donor phase were derived and the permeation profiles were analyzed as a function of time to determine the Kc values. The Kc values determined using the membrane permeation technique were in close agreement with those determined by the conventional kinetic method and the solubility method. The membrane permeation technique is of greater advantage than the conventional methods, because in the former method the stability constant can be obtained from only one experimental run by analyzing the permeation data as a function of time. In the latter method, on the other hand, some property changes have to be measured at various CyD concentrations and in turn analyzed as a function of CyD concentration. The permeation profiles of phenacetin of the drug-competing agent-beta-CyD ternary system were estimated by using the stability constants and the experimental curves closely matched the theoretically derived ones.

Algorithms↗
PubMed1999

Pain-free intralesional injection of triamcinolone for the treatment of keloid.

Intralesional injection of triamcinolone acetonide (TA) for the treatment of keloid is painful, and lidocaine-mixed preparations are much the same. I have injected TA (10 mg/ml) at the speed of 3-6 ml/hour using an electric syringe pump 40 times for the treatment of 10 keloids, 18 times without lidocaine and 22 times with lidocaine. The 95% confidence intervals (CI) of the 100 mm visual analogue pain scale of the TA alone group and the lidocaine-mixed group were 2.0 to 9.5 mm and 1.0 to 6.7 mm respectively, suggesting that both are practically pain-free. The speed of injection is an important determinant of pain in intralesional chemotherapy. The injection should be extremely slow and lidocaine should be added for sensitive patients.

Glucocorticoids↗
PubMed1999

Roles of three histidine kinase genes in hyphal development and virulence of the pathogenic fungus Candida albicans.

The pathogenic fungus Candida albicans harbors three histidine kinase genes called CaSLN1, CaNIK1, and CaHK1. The disruption of any one of these three genes impaired the hyphal formation and attenuated the virulence of C. albicans in a mouse systemic candidiasis model. The effects of the disruption on hyphal formation and virulence were most severe in the cahk1Delta null mutants. Although the double disruption of CaSLN1 and CaNIK1 was impossible, further deletion of CaSLN1 or CaNIK1 in the cahk1Delta null mutants partially restored the serum-induced hypha-forming ability and virulence. When incubated with radiolabelled ATP, the recombinant CaSln1 and CaNik1 proteins, which contained their own kinase and response regulator domains, were autophosphorylated, whereas CaHk1p was not. These results imply that in C. albicans, CaSLN1 and CaNIK1 function upstream of CaHK1 but are in distinct signal transmission pathways.

Animals↗
PubMed1999

Involvement of ATP-sensitive K(+) channels in spontaneous activity of isolated lymph microvessels in rats.

Physiological roles of ATP-sensitive K(+) channels for spontaneous activity in isolated rat mesenteric lymph microvessels (maximum diameter approximately 80-150 microm) were investigated. The lymph microvessels were cannulated with glass micropipettes and pressurized at a perfusion pressure of 6 cmH(2)O. Changes in the diameter and frequency of spontaneous contractions in the lymphatics were measured with videomicroscopy. Pinacidil (K(+)-channel opener) inhibited the spontaneous activity. In the presence of glibenclamide (selective ATP-sensitive K(+)-channel blocker; 10(-7) and 10(-6) M) and tetraethylammonium (TEA; nonselective K(+)-channel blocker; 10(-4) and 10(-3) M), the pinacidil-induced inhibition of the spontaneous contractions in lymph microvessels was significantly reversed. Glibenclamide and TEA themselves, however, did not affect the frequency of spontaneous activity in the lymph microvessels. These results suggest that ATP-sensitive K(+) channels are involved in the regulation of spontaneous activity in the smooth muscles of isolated lymph microvessels of rat mesenteries.

Adenosine Triphosphate↗
PubMed1999

Lung abscess caused by Paecilomyces lilacinus.

We report the case of a 57-year-old man who was referred to our department for further investigation of an abnormal chest shadow. Radiography on admission demonstrated a coin lesion in the right hilum. To make a final diagnosis, right middle lobectomy was performed and the mass was revealed to be a fungal abscess. Further examination confirmed that the fungus was Paecilomyces lilacinus. This is the first reported case of lung abscess caused by P. lilacinus in an otherwise healthy person.

Humans↗
PubMed1999

Determination of valproic acid in human serum by high-performance liquid chromatography with fluorescence detection.

A simple and highly sensitive high-performance liquid chromatographic method is described for the determination of valproic acid in human serum. The method is based on the direct derivatization of serum sample with 6,7-methylenedioxy-1-methyl-2-oxo-1,2-dihydroquinoxaline-3-ylpr opionohydrazide. The derivatization reaction proceeds in aqueous solution in the presence of pyridine and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide at 37 degrees C. The resulting derivatives were separated on a reversed-phase column (YMC Pack ODS-A) with isocratic elution and were fluorimetrically detected at 440 nm with excitation at 365 nm. The detection limit (signal-to-noise ratio=3) for valproic acid added to serum sample was 0.1 microg (700 fmol)/ml serum sample (2.3 fmol on column). The method was applied to determine the unbound- and total-valproic acid levels in the serum obtained from three healthy volunteers after oral administration of the drug (600 mg).

Adult↗
PubMed1999

[Microcirculation in the brain: viewpoint of autoregulation].

The cerebral blood flow (CBF) is autoregulated to a steady flow within certain ranges. CBF increases and cerebrovascular resistance (CVR) decreases dramatically with breakthrough of autoregulation when systemic arterial blood pressure exceeded the upper limit of the range. Many kinds of components in the brain as well neurogenic factors affect the autoregulation. The breakthrough of autoregulation does not occur in the presence of nitric oxide (NO) synthesis inhibitors, angiotensin converting enzyme inhibitor, prostanoids (PG) administered in the brain, sympathetic denervation, and sinoaortic denervation. The abolishment of breakthrough of autoregulation may be due to an increased tolerance of cerebral vessels to hypertension and the inhibition of the release of a vasodilator substance such as NO or PG. It appears that the tone of brain microvessels is controlled towards dilation by cholinergic innervation originating from the nucleus basalis of Meynert, glutamatergic or GABAergic mediated GABAA receptor, and by a mediator such as NO, bradykinin, PGs. Also, it is likely that candidates for constricting factors in intraparenchymal microvessels are norepinephrinergic from the superior cervical ganglion, serotonergic involved in 5-HT1D beta- and 5-HT2B-specific receptor subtypes, GABAergic mediated GABAB receptor, thromboxane, PG F2 alpha and the angiotensin system. The autoregulation of CBF is maintained by these neurogenic factors to prevent brain ischemia and hyperemia.

Angiotensin II↗
PubMed1999

cDNA cloning and chromosomal mapping of rat Smad2 and Smad4 and their expression in cultured rat articular chondrocytes.

Smad proteins are known to transduce signalling of TGF-beta receptor superfamily. We report here the entire sequences of rat Smad2 and Smad4 which have not been identified yet. Entire sequences were identified by degenerated polymerase chain reaction and following phage library screening and 5' RACE. The predicted amino acid sequences of rat Smad2 and Smad4 are highly conserved among rat, human and mouse. We also mapped these Smads to chromosome 18q.12.3. Unlike endothelial cells, TGF-beta1 stimulates articular chondrocyte proliferation as well as extracellular matrix production, and acts as a repairing agent against cartilage destruction. Since both Smad2 and Smad4 are essential factors for TGF-beta signalling, we examined their expression and regulation in cultured articular chondrocytes. Northern blot analysis showed that TGF-beta1 significantly increased the mRNA level of Smad2 but not of Smad4 in a dose- and time-dependent manner, suggesting that the augmentation of TGF-beta1 action is caused by increasing the expression of the downstream signalling molecule.

Amino Acid Sequence↗
PubMed1999

Various extrahepatic manifestations caused by hepatitis C virus infection.

It has been reported that hepatitis C virus (HCV) causes not only liver disease but also disorders of other organs and tissues. Previously, many HCV-related extrahepatic manifestations have been reported. In this study, we report 2 patients in whom tongue cancer was detected during the treatment of HCV-related liver disease. In one patient, tongue cancer was detected during the treatment of HCV-related liver cirrhosis, and articular rheumatism developed thereafter. The duration of HCV-related liver disease was 10 years. In the other patient, tongue cancer was detected during the treatment of HCV-related hepatocellular carcinoma. This patient had a past history of thyroid disease. The duration of HCV-related liver disease was 6 years. In these patients, the possibility that several conditions incidentally and concurrently developed cannot be denied. However, the conditions described above may be regarded as HCV-related extra-hepatic manifestations. In patients with HCV infection, it is important to examine conditions in organs other than the liver. Careful follow-up is needed.

Aged↗
PubMed1999

Contribution of nitric oxide to the presynaptic inhibition by endothelin ETB receptor of the canine stellate ganglionic transmission.

We previously reported that endothelin (ET) 3 inhibited presynaptically the dog stellate ganglionic transmission. Here, we report the investigation of the possible involvement of nitric oxide pathway in the endothelin-induced inhibition of the ganglionic transmission. The amount of acetylcholine released by preganglionic stimulation for 10 min was concentration-dependently inhibited after exposure to ET-3 (10(-9)-10(-6) M) or IRL-1620, endothelin ET(B) receptor agonist (10(-8)-10(-5) M). The inhibition was antagonized by pretreatment with a nonselective endothelin receptors antagonist (bosentan) and an ET(B) receptor antagonist (BQ-788) or a neuronal nitric oxide synthase inhibitor, 3-bromo-7-nitroindazole, but was not inhibited by a selective ET(A) receptor antagonist, BQ-123. The reduction induced by ET-3 was also antagonized by treatment with a selective inhibitor of soluble guanylyl cyclase, 1H-[1,2, 4]oxadiazolo[4,3-a]quinoxalin-1-one. In addition, similar reductions were also mimicked by exposure to cGMP analog, 8-bromoguanosine-3, 5-cyclic monophosphate and nitric oxide donor, S-nitroso-N-acetylpenicillamine. Exposure to ET-3 or IRL-1620 for a 30-min period increased the levels of total nitric oxide (NO), nitrite plus nitrate NO(x) concentration in the incubation medium, with the increase in NO(x) also being antagonized by BQ-788 at the same concentration. The ET-3-induced increase in NO(x) was antagonized by treatment with the same concentration of 3-bromo-7-nitroindazole or a selective inhibitor of receptor-mediated Ca(2+) entry, 1-[b-[3-(4-methoxyphenyl) propoxy]-4-methoxyphenethyl]-1H-imidazole (10(-5) M), and with a calmodulin antagonist, N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide. These results indicate that ET(B) receptor activation inhibits the sympathetic ganglionic transmission via reducing acetylcholine release from presynaptic nerve terminals, although this inhibition also seems to involve the ET(B) receptor-operated Ca(2+)-calmodulin-dependent activation of endogenous nitric oxide production.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1999

[Lung and bone marrow granulomas associated with human parvovirus B19 infection].

A 56-year-old man was admitted with flu-like symptoms, and his platelet count abruptly decreased. A chest X-ray film showed granular shadows, and lung and bone marrow specimens disclosed non-caseating epithelioid cell granulomas. The patient's serum IgM titer for human parvovirus (HPV) B19 was elevated. Our conclusion was that HPV B19 must be kept in mind as a possible pathogenic agent of granuloma formation.

Antibodies, Viral↗
PubMed1999

Hepatic heme metabolism in rats with fever induced by interleukin 1beta.

We have recently reported that the content of hepatic cytochrome P450 (CYP) apparently decreased in fever model rats, which were created by repeated injection of recombinant human interleukin-1beta (rhIL-1beta) into the cerebroventricle. To make clear the biochemical mechanism of the decreased CYP content, we examined the effect of fever on the activities of hepatic enzymes involved in the biosynthetic and degradative pathways of heme. The activities of delta-aminolevulinic acid synthase, a rate-limiting enzyme in the heme biosynthesis, and porphobilinogen synthase in the liver of rhIL-1beta-induced fevered rat were significantly lower than those in the control, whereas the activity of heme oxygenase, a key enzyme in the heme-degradative pathway, markedly increased in the fevered rat. Moreover, the heme saturation of tryptophan 2,3-dioxygenase in the fevered rat liver was decreased to 43% of the control. These results indicate that fever diminishes the hepatic heme content by decreasing the heme biosynthesis and by accelerating the heme degradation. The deficiency of hepatic heme pool may be one of the main mechanisms that cause the impairment of CYP synthesis.

5-Aminolevulinate Synthetase↗
PubMed1998

Renal effects of endothelin in anesthetized rabbits.

Intrarenal arterial infusion of endothelin-1 (1, 3 and 10 ng/kg per min) reduced renal blood flow, urine flow rate and urinary Na+ excretion without affecting fractional Na+ excretion in anesthetized rabbits. An endothelin ET(A) receptor antagonist (R)2-[(R)-2-[(S)-2-[[1-(hexahydro-1H-azepinyl)]carbonyl]amino-4-me thyl-pentanoyl]amino-3-[3-(1-methyl-1H-indolyl)]propionyl]amino-3-(2-pyr idyl)propionic acid (FR139317, 1 microg/kg per min) attenuated the endothelin-1 (1 ng/kg per min)-induced renal responses. An endothelin ET(B) receptor antagonist N-cis 2,6-dimetylpiperidinocarbonyl-L-gamma-metylleucyl-D-1-met hoxycarbonyltryptophanyl-D-norleucine (BQ-788, 1 microg/kg per min) potentiated the endothelin-1-induced changes in renal blood flow, urine flow rate and urinary Na+ excretion. A nitric oxide (NO) synthase inhibitor Nomega-nitro-L-arginine methyl ester (L-NAME, 50 microg/kg per min) also potentiated the endothelin-1-induced reductions in urine flow rate and urinary Na+ excretion but not the reduction in renal blood flow. Endothelin-1 reduced fractional Na+ excretion in the presence of BQ-788 or L-NAME. A spontaneous NO donor 1-hydroxy-2-oxo-3-(N-methyl-3-aminopropyl)-3-methyl-1-triazene (30 ng/kg per min) slightly attenuated the antinatriuresis but not the vasoconstriction induced by endothelin-1. These results suggest that in the rabbit kidney in vivo endothelin ET(A) receptors mediate endothelin-1-evoked vasoconstriction and tubular Na+ reabsorption, that the concomitant stimulation of endothelin ET(B) receptors by endothelin-1 counteracts both the ET(A) receptor-mediated vascular and tubular actions, and that the tubular action, but not the vascular action, of endothelin-1 is also susceptible to changes in renal NO level.

Analysis of Variance↗
PubMed1998

Synthesis and pharmacological activities of 13-dehydro derivatives of primary prostaglandins.

13-Dehydro derivatives of prostaglandin E1, E2, E3, F1 alpha and F2 alpha were synthesized. Compared with natural prostaglandins, 13-dehydro analogues were found to exhibit more potent inhibitory activity against human platelet aggregation and relaxation of guinea-pig isolated trachea, while they showed less potent activity of contraction of guinea-pig isolated ileum.

Animals↗