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Biomedical subjects

H Noguchi

Publications and source records attributed to H Noguchi.

At least 289 records · Page 16Linked to original sources
PubMed1990

[A case of severe infantile form of congenital nemaline myopathy with extensive fatty replacement of the skeletal muscles].

A case of severe infantile form of congenital nemaline myopathy who developed extensive fatty replacement of the skeletal muscles was described. A girl was born with severe hypotonia and flaccidity of the extremities. She was put on a ventilator because of the severe respiratory insufficiency. Muscle biopsy performed at 3 months of age revealed numerous nemaline rods in myofibers. She had an anoxic episode at 2 years of age and fell into a vegetative state after that. Serum creatine kinase and aldolase levels were normal. At 8 years of age, X-ray CT scan of the skeletal muscles revealed diffuse and severe fatty replacement of the skeletal muscles of the trunk and extremities; this was far more extensive than in the case of Duchenne muscular dystrophy of similar age. Second muscle biopsy performed in the anterior tibialis muscle at the age of 8 years revealed atrophic muscle fibers and extensive proliferation of connective and fatty tissues. Electron microscopy revealed, numerous rod-containing muscles fibers with severe disorganization and loss of myofilaments. Sural nerve biopsy performed at the same time showed decreased number of large myelinated fibers. Although a possibility could not be excluded completely that the episode of anoxia and chronic debilitation may have contributed to these pathological neuromuscular findings, it was presumed that severe degeneration and fatty replacement of the skeletal muscles progress rapidly after birth in some cases of severe infantile form of congenital nemaline myopathy.

Adipose Tissue↗
PubMed1990

[A case report of descending thoracic aortic aneurysm associated with anterior spinal artery syndrome despite no marked ESP changes].

A 67-year-old man underwent graft replacement for the descending thoracic aortic aneurysm with the aid of temporary external bypass. Intraoperative evoked spinal potentials (ESPs) were monitored to detect the spinal cord ischemia. Incomplete paraplegia with sensory dissociation was developed in this patient after surgery, despite well maintained ESPs throughout the aortic cross-clamping. ESPs have been widely used as a mean of detecting early impairment of spinal neural conduction during aortic surgery. However, ESPs are principally mediated through posterior and lateral column pathways and they are not always a reliable monitor to predict paraplegia in aortic surgery.

Aged↗
PubMed1990

Novel cardioprotective effects of TYB-3823 on ischemic damage in the working hearts of rats: comparison with lidocaine.

The cardioprotective effects of a new antiarrhythmic drug, TYB-3823 [1-(2,6-dimethylphenyl)-dimethylaminoguanidine hydrochloride] were examined in the working hearts of rats and compared with those of lidocaine. Before ischemia, TYB-3823 at 5 x 10(-5) M produced a slight negative inotropic effect, resulting in a decrease in aortic flow and cardiac output. However, at lower concentrations (10(-6) and 10(-5) M), the drug had no significant effect on the functional cardiac parameters before ischemia. Lidocaine at such concentrations also had no effect. Global ischemia for 15 min decreased cardiac function rapidly which only recovered partially, with a delay, after reperfusion in the control hearts. Treatment with TYB-3823 accelerated the time course of recovery during reperfusion markedly, significantly improving functional cardiac parameters. However, lidocaine had little effect on recovery of function. Reperfusion-induced arrhythmia was equipotently inhibited by TYB-3823 and lidocaine. Leakage of cytosolic enzymes (lactate dehydrogenase, creatine phosphokinase and alpha-hydroxybutylic dehydrogenase) during reperfusion was inhibited more effectively by TYB-3823 than lidocaine. Light microscopic and electron microscopic examinations revealed that treatment with TYB-3823 protected against the histological damage induced by ischemia, such as hyaline degeneration of myocardium, absence of cross-striation and swelling of mitochondria. These results suggest that, unlike lidocaine, TYB-3823 causes a novel cardioprotective effect through unknown mechanisms in addition to its antiarrhythmic action.

Animals↗
PubMed1989

[An assessment of therapeutic effects by transcatheter arterial embolization (TAE) with degradable starch microspheres (DSM) for hepatic malignant tumors].

Transcatheter arterial embolization (TAE) by using degradable starch microspheres (DSM) as embolic material, 40 microns in diameter and degraded by serum amylase within one hour, was carried out for thirteen cases with hepatic malignancies including eleven cases with hepatocellular carcinoma (HCC), one case with cholangiocarcinoma and one case with metastatic liver cancer. DSM were mixed with anticancer agents and administered through the catheter, which was introduced by Seldinger's method, via the hepatic artery immediately after hepatic angiography in ten cases and through subcutaneously implanted drug delivery system (Port-A-Cath) in three cases. The dose of DSM was 900 mg/body and adriamycin 30-40 mg/m2 or 12-14 mg/m2 were used. The former was administered through the catheter immediately after angiography and the latter through Port-A-Cath for HCC and cholangiocarcinoma. A same dose of DSM and mitomycin C 15-16 mg/m2 was administered for metastatic liver cancer through the catheter immediately after angiography. The administration was repeated weekly in three cases in which Port-A-Cath was implanted, and at five weeks' interval through the catheter immediately after hepatic angiography in the other ten cases. Therapeutic effects were assessed and pharmacokinetics of adriamycin were studied. Results were as follows; 1) Partial response (PR) was obtained in five cases out of eleven cases with HCC (45.5%) and there were three cases with minor response (MR) in the other six cases. Totally, decrease of tumor size was demonstrated in eight cases out of eleven cases (72.7%). 2) In nine cases in which AFP was positive, the titer of AFP was decreased in seven cases (77.8%). 3) No change (NC) was obtained in cholangiocarcinoma.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoma, Bile Duct↗
PubMed1989

Gas chromatographic assay and disposition of 6-chloro-2-pyridylmethyl nitrate, a new antianginal drug, in healthy volunteers.

Quantitative determinations of plasma concentrations of 6-chloro-2-pyridylmethyl nitrate, a new antianginal drug, and its urinary metabolite, 6-chloro-2-pyridinecarboxylic acid (metabolite 1), were obtained using GC with a 63Ni electron-capture detector. 6-Chloro-2-pyridylmethyl nitrate was extracted from plasma with n-pentane. Metabolite 1 was extracted from acidic urine with ethylacetate, back extracted with 0.1 M NaHCO3, and methylated with boron trifluoride methanol reagent. The internal standard for metabolite 1 determination was prepared by propylation of metabolite 1 with boron trifluoride n-propanol reagent. The formation of the esters was confirmed by the GC-MS results. These methods proved to be sensitive and reproducible. A single dose of 6-chloro-2-pyridylmethyl nitrate (5, 10, 20, 40, or 60 mg) was given perorally to healthy volunteers. From the data, a large interindividual variability in the apparent plasma clearance was apparent (85.5 +/- 123 L/min; CV 144%). However, metabolite 1 was the main metabolite in human urine, and the interindividual variation was slight (CV 13%).

Administration, Oral↗
PubMed1989

Simultaneous high-performance liquid chromatography assay of two metabolites of 6-chloro-2-pyridylmethyl nitrate, a new antianginal drug, and its application to a pharmacokinetic study in rats.

An HPLC technique has been developed for the simultaneous determination of 6-chloro-2-pyridine methanol (5) and 6-chloro-2-pyridinecarboxylic acid (3), two metabolites of 6-chloro-2-pyridylmethyl nitrate, a new antianginal drug, in rat plasma. The plasma sample was placed on a Bond Elut C18 column and the compounds were eluted with 250 microL of the mobile phase. A 50-150-microL aliquot was injected onto the HPLC column. No interfering substances were observed in the plasma of a normal rat. The calibration curves for both 5 and 3 were linear from 0.1 to 50 micrograms/mL. However, the quantitative detection of the two additional metabolites, N-(6-chloro-2-pyridylcarbonyl)-glycine (1) and N-acetyl-S-(6-chloro-2-pyridylmethyl)-L-cysteine (2) was not satisfactory. The metabolic pathway of 6-chloro-2-pyridylmethyl nitrate in vivo was studied in male rats which were dosed separately with 6-chloro-2-pyridylmethyl nitrate, 5, and 3. After intravenous injection of 6-chloro-2-pyridylmethyl nitrate, the unchanged drug was determined by a GC method that was also developed by us and reported in another paper. 6-Chloro-2-pyridylmethyl nitrate was rapidly metabolized, and the metabolites were detected as early as 1 min after 6-chloro-2-pyridylmethyl nitrate administration. The parent compound then declined rapidly and 3 formation was confirmed in the rat plasma. 6-Chloro-2-pyridylmethyl nitrate is extensively metabolized to 3 via 5 formation, and 3 is the main metabolite in rat plasma.

Animals↗
PubMed1989

Heterogeneity of the L-rhamnose residue in the outer core of Pseudomonas aeruginosa lipopolysaccharide, characterized by using human monoclonal antibodies.

Hybridoma cell lines producing human monoclonal antibodies (MAbs) MH-4H7 and KN-2B11 [immunoglobulin M (lambda)] which bound to the outer core region of Pseudomonas aeruginosa lipopolysaccharide (LPS) were established by cell fusion of human peripheral lymphocytes with human-mouse heteromyeloma SHM D-33. Both binding specificity experiments with a series of LPS-defective mutants derived from P. aeruginosa PAC1R (P. S. N. Rowe and P. M. Meadow, Eur. J. Biochem.132:329-337, 1983) and competitive enzyme immunoassay experiments with monosaccharides demonstrated that alpha-L-rhamnose residues in the outer core of LPS might be in part an epitope. The MAbs specifically bound to clinical isolates belonging to Homma serotypes A, F, G, and K at a frequency of 70 to 86% and to serotypes H and M isolates at about 50%. They did not bind to any isolates of serotype B, E, and I tested. This evidence indicates that L-rhamnose and probably its neighboring residues in the other core of P. aeruginosa are heterogeneous in some association with the O serotype.

Adult↗
PubMed1989

A new antitumor antibiotic, FK973: its metabolism in the blood and the antitumor effects of its metabolites on experimental models.

Our previous studies showed that a new, substituted dihydrobenzoxazine, FK973 (11-acetyl-8-carbamoyloxymethyl-4-formyl-14-oxa-1,11-diazatetracyclo+ ++- [7.4.1.0(2,7).0(10,12)tetradeca-2,4,6-trien-6,9-diyl diacetate), which is a triacetylated derivative of the fermentation product FR900482 of Streptomyces sandaensis No. 6897, had potent antitumor effects on experimental tumors in vivo and in vitro. In the present study, we investigated the metabolism of FK973 in the blood of human and animals and the antitumor effects of its metabolites. After the incubation of FK973 in the blood (hemolysate) or serum of humans, dogs, rats and mice, it was rapidly metabolized to two diacetates and a monoacetate, and slowly to FR900482. FK973 and all its deacetylated metabolites showed strong cytotoxicity on in vitro cultured murine L1210 leukemia cells, and the cytotoxicity of FK973 was the most potent. In the vivo experiments, FK973 and its metabolites prolonged the life of mice bearing ascitic P388 leukemia, and it potently inhibited the growth of murine B16 melanoma and Colon 38 adenocarcinoma implanted subcutaneously in mice. FK973 was the most effective compound. Thus, these results suggest that the antitumor effects of FK973 are stronger than those of its deacetylated metabolites produced in the blood of humans and animals.

Animals↗
PubMed1989

Monoclonal antibodies which preferentially bind to 22 K human growth hormone rather than its 20 K variant.

We have established 13 hybridoma cell lines which secrete mouse IgG1 monoclonal antibodies (McAbs) to human growth hormone (hGH). Binding affinity and binding specificity of McAbs were analyzed by competitive radioimmunoassay. Among these McAbs, CL. B1 showed a high affinity of 9.8 x 10(8) l/mol, and all McAbs so far tested showed very weak cross-reactivity or none at all with human prolactin (hPRL) and human chorionic somatomammotropin (hCS; human placental lactogen). Analysis of binding sites of McAbs using hGH variant and fragments in both ELISA and RIA demonstrated that McAbs could be classified into two groups. All the McAbs obtained in this study bound to plasmin-digested fragment S2 (hGH 1-134 and 141-191) and fragment alpha 3 (hGH 1-134 and 147-191). However, five (such as 1D2) out of 13 McAbs bound to fragment F1 (hGH 1-134) and others (such as CL. B1) did not. The McAb CL. B1 in the latter group showed low affinity with 20 K hGH (residue 32-46 deleted in native 22 K hGH) in contrast to high affinity with hGH (22 K). This suggests that the former McAbs recognize an epitope located at the N-terminal two-third part of hGH. In contrast, the McAbs of the latter group are likely to recognize three-dimensional structure of native 22 K hGH.

Animals↗
PubMed1989

Arterial-venous concentration gradient as a potential source of error in pharmacokinetic studies. Plasma concentration differences of 6-chloro-2-pyridylmethyl nitrate on constant infusion to rats.

1. Plasma concentrations of 6-chloro-2-pyridylmethyl nitrate (CPMN) at different sampling sites in the circulation were determined during and after constant infusion in the rat. 2. An arterial-venous CPMN concentration gradient was found and characterized by the following trends. During CPMN infusion into the right atrium, plasma concentrations were higher in arterial (aortic arch) than venous (inferior vena cava) plasma. After cessation of infusion the venous plasma concentrations were significantly higher (P less than 0.05) than those in arterial samples. There was a low concentration gradient between the right atrium and the peripheral artery, but substantial difference between the peripheral artery and the vein. There was a 1.8-2.4 extraction ratio of CPMN across the arterial-venous bed.

Animals↗
PubMed1989

Sex differences in the metabolism and excretion of nilvadipine, a new dihydropyridine calcium antagonist, in rats.

1. The metabolic profiles of nilvadipine in the urine and bile of male and female rats were studied after i.v. dosing with 1 mg/kg of the 14C-labelled compound. 2. Excretion rates of the dosed radioactivity in male and female rats, respectively, in the first 48 h were 84.1% and 59.1% in bile, 12.0% and 36.9% in urine, and 2.5% and 3.6% in faeces. 3. Comparison of biliary and urinary excretion for each radioactive metabolite after dosing with 14C-nilvadipine, showed marked sex-related differences in the excretion routes of several metabolites. In male rats, metabolite M3, having a free 3-carboxyl group on the pyridine ring, was not excreted in urine, but in female rats urinary excretion of M3 accounted for 4.7% of the dose. One reason for the lower urinary excretion of radioactivity by males than by females was that the main metabolite, M3, was not excreted in the urine of the male rats. 4. To clarify the sex difference in the route of excretion of M3, this metabolite (M3) was given i.v. to rats. No excretion of the metabolite was observed in urine of male rats within 24 h but, in marked contrast, 41.5% of the dose was excreted in urine of females in the same period.

Animals↗
PubMed1989

[Chemotherapy with Cisplatin-Phosphatidyl-choline-Lipiodol (CPL) suspension in unresectable hepatocellular carcinoma].

Twenty-seven patients with unresectable hepatocellular carcinoma (HCC) were treated with Cisplatin-Phosphatidyl-choline-Lipiodol (CPL) suspension. PR was obtained in two of ten cases (20%) by one shot therapy. AFP decreased in 9 of 10 patients by one shot therapy with a 62.1% rate of decrease. In all of 13 patients by TAE, AFP decreased and the rate of decrease was 64.8%. The concentration of CDDP in the peripheral venous blood was lower and continued longer than that of CDDP on the market. Nausea, vomiting and fever were noted in most cases as adverse effects, but they were slight. These results suggest that CPL agents were very chemotherapeutic for unresectable HCC.

Carcinoma, Hepatocellular↗
PubMed1989

[Properties of dental cyanoacrylate cement "FH" in the early period of setting].

The properties of dental cyanoacrylate cement "FH", which has protective and bacteriostatic effect on dental pulp, were compared with that of glass-ionomer cement. The operational properties such as setting time and consistency were good, but the mechanical properties as dental cement were a little inferior. These properties were affected definitely by temperature and humidity than the glass-ionomer cement, especially the influence of humidity was very high. However, the influence on bond strength was almost nothing, especially in the early period of setting. The factors affecting it could be very low disintegration. The bond strength for dentin after 24 hours the start of mixing of FH cement was much higher than that for enamel, but the strength rapidly decreased by thermal cycling between 4 degrees C and 50 degrees C in water.

Cyanoacrylates↗
PubMed1989

[Study on clinical standard consistency of the luting cement].

Various properties of dental luting cement are influenced by powder/liquid ratio. The standard consistency of luting cement is determined in Japanese industrial standard and American dental association's specifications. However, it is not considered that a constant consistency is best for luting cement of all kinds. This study were performed on suitable consistency of individual cement with regard to bond strength and disintegration. Most suitable consistency was almost the same as standard consistency by the specification in the case of Zinc phosphate cement (GC's Elite cement 100). But, in the case of Polycarboxylate cement (Shofu's HY-Bond carbo cement) and Glass alkynoate cement (GC's Fuji ionomer Type I Liv), maximum bond strength can be obtained with a more powder/liquid ratio than standard consistency by the specification. Especially, Glass alkynoate cement shows this tendency strongly. Therefore, it must be manipulated quickly after mixing.

Dental Bonding↗
PubMed1989

Stereoselective disposition of nilvadipine, a new dihydropyridine calcium antagonist, in the rat and dog.

The stereoselective disposition of nilvadipine (NV), a new 1,4-dihydropyridine calcium antagonist, was determined in male and female rats, and male dogs. After oral dosing of racemic NV to male rats, the maximum plasma concentration (Cmax) and area under the plasma concentration-time curve (AUC) of the pharmacologically more potent (+)-NV were 0.59-0.60 times those of (-)-NV. The apparent oral clearance (CLo) ratio of (+)- to (-)-NV was 1.69. The plasma elimination of the enantiomers were similar. In female rats, the plasma concentrations and pharmacokinetic parameters of the enantiomers did not significantly differ. In orally-dosed dogs, the Cmax and AUC of (+)-NV were 3.13 and 3.83 respectively times greater than those of (-)-NV. The enantiomeric ratio of CLo was 0.27, and the half-lives of the enantiomers were similar. After intravenous dosing to dogs, the plasma concentrations of (+)- and (-)-NV declined biexponentially with similar t1/2 beta values. The AUC of (+)-NV was 1.56 times more than that of (-)-NV. The enantiomeric ratios of systemic clearance and volume of distribution at steady state were 0.64 and 0.81, respectively. Thus, the stereoselective disposition of NV was species-dependent and sex-related in rats, and was dosing route-dependent in dogs. The free fraction value for protein binding of (+)-NV in dog plasma was only 0.50-0.51 times that of (-)-NV. The enantiomeric ratios of those values in male and female rat plasma were 1.14 and 0.98, respectively.

Administration, Oral↗
PubMed1989

Arterial-venous plasma concentration differences of 6-chloro-2-pyridylmethyl nitrate in humans after sublingual administration.

The plasma concentrations of 6-chloro-2-pyridylmethyl nitrate after sublingual administration were determined in six healthy male volunteers (venous plasma) and eleven patients (arterial plasma) with ischemic heart failure. The pharmacokinetics of the compound was investigated in volunteers. Plasma concentration-time data in each volunteer were found to fit a two-compartment open model with zero-order absorption. The pharmacokinetic parameters estimated from curve-fitting the plasma concentration-time data were as follow: Tmax 10 +/- 2.8 min, Cmax 8.16 +/- 2.48 ng/mL and CLP 6.16 +/- 1.79 L/min (means +/- S.D.). The arterial plasma concentrations (11.9 +/- 5.14 ng/mL) 7 min after sublingual administration were significantly higher (p less than 0.05) than those in venous samples (6.86 +/- 2.80 ng/mL). These results support that the arterial-venous gradient exists after administration of 6-chloro-2-pyridylmethyl nitrate in humans.

Administration, Sublingual↗
PubMed1989

[A case of retrograde amnesia of 22 years, continued for 4 days following a general anesthesia accompanied by a permanent amnesia of these 4 days after the complete recovery from the retrograde amnesia].

A case of global amnesia which continued for 4 days following a general anesthesia and recovered without any neurological deficits was reported. The patient was a 38-year-old woman suspected of lung cancer, and scheduled for pulmonary lobectomy. She had a history of appendectomy under spinal anesthesia 22 years before. She was premedicated with diazepam (10mg), atropine (0.5mg) and pentazocine (30mg). Anesthesia was induced with thiamylal (500mg) and succinylcholine (140mg) iv and 100% oxygen. Anesthesia was maintained with enflurane and nitrous oxide with oxygen for 3 hours. After her recovery from anesthesia, a retrograde amnesia of 22 years was observed and continued for 4 days. Then the memory was restored completely, but the amnesia during these 4 postoperative days remained permanently. We have documented the case of amnesia in the immediate postoperative period which is similar to transient global amnesia. It seems likely that this amnesia was caused by drug interaction, hypoxia, decreased cerebral perfusion or psychogenic effects of general anesthesia.

Adult↗