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Biomedical subjects

A Noda

Publications and source records attributed to A Noda.

At least 91 records · Page 5Linked to original sources
PubMed1998

Enantioselective N-acetylation of N-desisopropylpropranolol by rat liver acetyltransferase.

The enantioselective N-acetylation of N-desisopropylpropranolol (NDP), one of the main metabolites of propranolol (PL), by rat liver acetyltransferase (AT), was investigated. R(+)-NDP or S(-)-NDP was used as a substrate at concentrations ranging from 10 to 200 microM. The cytosol fraction of a rat liver containing 3.93 mg protein/ml served as the source of AT. For 1-amino-3-(1-naphthyloxy)-2-propanol (AcNDP) formation from R(+)-NDP or S(-)-NDP in the presence of infinite AcCoA (250 microM), the Km value was calculated to be 67.5 or 62.4 microM, and the Vmax value was 0.462 or 0.205 nmol/min/mg protein. Based on these findings, the enantioselective N-acetylation of NDP was proved, i.e., AcNDP formation from R(+)-NDP was found to take place more easily than that from S(-)-NDP. Furthermore, AcNDP formation from NDP was competitively inhibited by the exogenous arylamine, p-aminobenzoic acid (PABA), which is well-known to be a typical substrate of AT. The presence of enantioselective inhibition for AcNDP formation was thus confirmed based on the Ki values, 440 microM in the case of R(+)-NDP and 250 microM in the case of S(-)-NDP, respectively, i.e. two-fold enantioselective inhibition was demonstrated based on the Ki values in S(-)-enantiomer in comparison with R(+)-enantiomer.

4-Aminobenzoic Acid↗
PubMed1998

Participation of P450-dependent oxidation of isoniazid in isonicotinic acid formation in rat liver.

By determining the formation amount of isonicotinic acid (INA) from isonicotinic acid hydrazide (isoniazid:INH) in isolated rat hepatocytes, we were able to identify the involvement of the oxidative cleavage of the acid hydrazide. INA formation from INH increased significantly using the isolated hepatocytes prepared from rats pretreated with phenobarbital (PB), 3-methylcholanthrene (3MC), dexamethazone (DEX) and rifampicin (RIF), respectively, in comparison to the control group. On the other hand, a remarkable decrease in INA formation from INH was observed by the addition of such P450 inhibitor as metyrapone or cimetidine as well as an amidase inhibitor bis(p-nitrophenyl)phosphate (BNPP) to the isolated hepatocytes prepared from PB-pretreated rats. By further experiments using rat hepatic microsomes, the oxidative pathway of INA formation in INH metabolism was determined to be P450-dependent, since NADPH and oxygen were both essential for the oxidative pathway of INH to INA and the amount of INA formation was also significantly increased by P450 inducers. Regarding acetylisoniazid (AcINH) and isonicotinic acid amide (INAA), however, INA formation by P450 was little observed in the microsomal experiments.

Animals↗
PubMed1998

A fatal Pegosomum sp. (Trematoda: Echinostomatidae) infection in a wild cattle egret (Bubulcus ibis) from Japan.

An adult cattle egret (Bubulcus ibis) caught in Kobe of Hyogo Prefecture, Japan, in December 1995 died of a severe infection associated with the trematode parasite Pegosomum sp. At necropsy, 22 trematode parasites were found in the lumen of the bile duct, and the duct wall was markedly thickened. Histopathologically, severe cholangitis and cholecystitis were observed in close association with the parasites in the bile duct. Severe Pegosomum sp. infection may be one of the factors contributing to the mortality of wild cattle egrets. This is the first reported case of the genus Pegosomum infection in wild birds of Japan.

Animals↗
PubMed1998

[The relationship between subjective sleepiness and polysomnographic findings in sleep apnea syndrome].

We investigated factors of daytime sleepiness in 22 middle-aged male patients with sleep apnea syndrome (SAS) using the Epworth sleepiness scale (ESS) and polysomnography. The subjects were classified into two groups according to ESS score as follows; low ESS group: ESS score < 10, and high ESS group; ESS score > or = 10. ESS score was significantly correlated with duration in which nocturnal oxygen saturation decreased below 90% (Time of SpO2 < 90%) (r = 0.54, p < 0.05). Time of SpO2 < 90% and percent of movement arousals at the termination of apnea/hypopnea (number of movement arousal/total number of apnea/hypopneas x 100) were significantly higher in high ESS group than in low ESS group. Our findings suggest that the severity of oxygen desaturation and sleep fragmentation caused by arousal response at the termination of apnea/hypopnea may be important factors of daytime sleepiness in patients with SAS.

Aged↗
PubMed1997

Suppressed cardiac and electroencephalographic arousal on apnea/hypopnea termination in elderly patients with cerebral infarction.

The goal of the present investigation is to show the clinical significance of arousal response at termination of apnea/hypopnea in patients with sleep apnea syndrome (SAS) after cerebral infarction. We polygraphically assessed "cardiac arousal," which is defined as an abrupt increase in heart rate at a termination of sleep apnea/hypopnea, and electroencephalographic (EEG) arousal. There were six elderly subjects, bedridden after cerebral infarction, with SAS aged 71-87 years (mean 72.3 years) and 11 age-matched patients with SAS aged 61-78 years (mean 62.3 years) as controls. The following sleep parameters were measured: number of apneas per hour (apnea index [AI]), number of hypopneas per hour (hypopnea index [HI]), summation of the two (apnea/hypopnea index [AHI]), and duration in which nocturnal oxygen saturation was decreased below 90% (duration of SaO2 < 90%). We calculated the ratio of apnea/hypopnea per hour with cardiac arousal to total apnea/hypopneas (XI) (% cardiac arousal [XI/AHI x 100]) and the ratio of that with EEG arousal (YI) (% EEG arousal [YI/AHI x 100]). Between the two groups, we found no significant difference in body mass index, the ratio of central apnea to total apnea/hypopnea, AHI, duration of apnea/hypopnea, lowest SaO2, and duration of SaO2 < 90%. Compared with controls, % cardiac and % EEG arousals were significantly lower in patients with cerebral infarction. In contrast, the ratio of HI to AHI was significantly higher in patients with cerebral infarction than in control subjects. Our findings indicate that cardiac and EEG arousals at termination of apnea/hypopnea are significantly suppressed in elderly patients with SAS after cerebral infarction, which may provide useful information on the pathophysiology of SAS in patients with cerebrovascular disease.

Aged↗
PubMed1997

Nitric oxide metabolites in the cisternal cerebral spinal fluid of patients with subarachnoid hemorrhage.

OBJECTIVE: To investigate nitric oxide (NO) metabolism after subarachnoid hemorrhage (SAH). METHODS: We measured the concentrations of the NO metabolites, nitrite and nitrate, in cerebrospinal fluid (CSF) obtained from the cisternal drainage of patients with SAH. Studies were performed for 31 patients who had undergone surgical obliteration of bleeding aneurysms within 3 days of their hemorrhage. The concentrations of nitrite and nitrate in the CSF were measured for 14 days using a nitrate/nitrite kit and samples that were obtained on a daily basis from the cisternal drainage. RESULTS: Compared with the control values in the CSF (2.6 +/- 0.4 mumol/L, n = 14) obtained from patients with hemifacial spasm, trigeminal neuralgia, or nonruptured aneurysms, the concentrations of nitrite and nitrate in the CSF were significantly elevated in the acute stage of SAH and remained elevated. The concentration of NO metabolites may correlate with the amount of bleeding, inasmuch as the values in patients in Fisher Group 3 (n = 25) were higher than those in patients in Fisher Group 2 (n = 6). The concentration of nitrate was higher than that of nitrite, suggesting that NO in the subarachnoid space is mainly absorbed by hemoglobin and degraded to nitrate. No differences were demonstrated in patients treated with high doses of methylprednisolone (n = 17) compared with those treated with usual-dose steroids (n = 14). Steroids are known to prevent the formation of inducible NO synthase mediated by inflammatory cytokines. CONCLUSION: NO metabolism in the brain is stimulated after SAH. Nitrate is the dominant NO metabolite in CSF after SAH. The involvement of inducible NO synthase in the pathophysiology of NO metabolism after SAH was not clearly suggested based on the present data.

Adult↗
PubMed1997

Advanced gastric carcinoma in a de Brazza's guenon (Cercopithecus neglectus).

A necropsy case of advanced gastric carcinoma in a 20-year-old female de Brazza's guenon (Cercopithecus neglectus) was studied, Grossly, an excavated carcinoma mass, 60 x 55 x 35 mm in size, was located in the cardiac region of the stomach. Multiple disseminated nodules had implanted on the diaphragm and omentum. The tumor consisted of intestinal-type adenocarcinoma cells and showed infiltrative growth beyond the serosa. The morphologic features of this tumor closely resembled those of advanced gastric carcinomas in human patients.

Adenocarcinoma↗
PubMed1997

beta-Adrenoreceptor antagonistic actions and mutagenicities of R(+)- and S(-)-enantiomers of N-desisopropylpropranolol and its N-acetyl conjugate.

Enantiospecific acetyl conjugation was examined in the rat liver 105000 x g supernatant (cytosol) system using racemic 1-amino-3-(1-naphthyloxy)-2-propanol (NDP), a N-desisopropyl metabolite of propranolol. From the results of chiral separative determination of the samples by HPLC using a Chiralcel OD-R column, more remarkable enantiospecificity was observed in the R(+)-enantiomer on NDP elimination and N-acetyl conjugate (AcNDP) formation. Next, the strength of beta-adrenoceptor antagonistic actions and mutagenicities was compared between R(+)- and S(-)-enantiomers of NDP and AcNDP, respectively. In the case of NDP, both enantiomers possessed weak beta1-adrenoceptor antagonistic effects on isoproterenol-induced positive inotropic and chronotropic actions in the left and right atria isolated from a guinea pig. These actions of R(+)- and S(-)-NDP were 1700-times and 100-times less potent, respectively, than those of propranolol. beta2-Adrenoceptor antagonistic actions of R(+)- and S(-)-NDP in the trachea were 1600-times and 200-times less potent, respectively, than those of propranolol. Enantiospecificity was observed in the beta-adrenoceptor antagonistic action of S(-)-NDP, while R(+)-NDP and both enantiomers of AcNDP appeared to be negligible in this action. On the other hand, the mutagenicities of each enantiomer were examined by the Ames method using 13 kinds of Salmonella typhimurium strains. In the case of AcNDP, the numbers of colonies increased according to the substrate concentration only when rat liver 9000 x g supernatant fraction (S-9 mixture) was added to the plates containing TA100, YG1029, TA104 and YG3003, and then enantiospecificity was observed in the mutagenicity of S(-)-AcNDP. Thus, the ultimate mutagen might be an active metabolite formed mainly from S(-)-AcNDP. Despite of the addition of rat liver S-9 mixture, R(+)-AcNDP and both enantiomers of NDP did not indicate mutagenicity.

Adrenergic beta-Antagonists↗
PubMed1997

[A novel epilepsy animal model (NER)].

A mutant showing convulsive seizures spontaneously in a CJ: Wistar colony was named the Noda epileptic rat (NER). The NER exhibits tonic-clonic convulsion without any external stimuli once every 30 h. However, we succeeded in inducing similar convulsive seizures by applying priming sound stimuli (95 dB, 8 kHz, 30 sec) from 3 weeks of age in all 24 NER examined. When the effects of clinically available antiepileptics were tested on the seizures of such primed NER, the most potent agents were carbamazepine, diazepam, valproate, phenobarbital and trimethadione, while phenytoin and zonisamide showed lower potency. Furthermore, ethosuximide was not effective in inhibiting the seizures. In hippocampal slices of NER with convulsive seizures, repetitive firing accompanied by long-lasting depolarization was observed when a single stimulation was delivered to the mossy fibers in the CA3 pyramidal cell. This depolarization shift was completely blocked with a Ca2+ antagonist (nicardipine 10 nM). The long-lasting hyperpolarization that followed the repetitive firing was also observed with mossy fiber stimulation in the hippocampal CA3 pyramidal cells of the NER. These findings suggest that Ca2+ channel abnormality of the hippocampal CA3 pyramidal cells may be involved in the convulsive seizures.

Animals↗
PubMed1997

[Evaluation of electrocardiographic left ventricular hypertrophy with both QRS voltage and ST-T change using echocardiography].

The purpose of the present study is to determine whether electrocardiographic QRS voltage criteria with ST-T change is useful in the diagnosis of left ventricular hypertrophy (LVH) using echocardiography. One hundred men including 59 with hypertension (HT), 9 with hypertrophic cardiomyopathy (HCM), and 32 without any cardiovascular disease were enrolled in this study. All of them had the electrocardiographic evidence of LVH by Sokolow-Lyon voltage criteria (RV5 or RV6 > 2.6 mV, SV1+RV5 or SV1+RV6 > or = 3.5 mV). They were classified into three groups based on ST-T pattern as follows: Normal ST-T (group N): normal ST-T in twelve leads; Early strain ST-T (group ES): ST depression, flat T (T/R < 1/10), diphasic T or T wave inversion < 0.1 mV in V5 or V6; and Strain ST-T (group S): inverted T wave in V5 and V6. Echocardiographic LVH was determined when either interventricular septal thickness (IVST) or left ventricular posterior wall thickness (LVPWT) > or = 12 mm was present. According to this echocardiographic evidence, 31.7%(20/63) of group N, 75.0% (12/16) of group ES, and 100% (21/21) of group S were diagnosed. There were significant correlations between QRS voltage indices (RV5, RV6, SV1+RV5 and SV1+RV6) and IVST, (IVST+LVPWT)/2, and LV mass in group S(r = 0.650 to 0.858, p < 0.05) but not in group N. Values for IVST and LV mass were significantly greater in group S than in group ES or N. The electrocardiographic diagnosis of LVH with both QRS voltage and ST-T change thus appeared to be more useful than that with QRS voltage criteria alone.

Adult↗
PubMed1997

[Mitral valve prolapse and autonomic activity in normal women].

We examined relationships between mitral valve prolapse (MVP) and circadian rhythm of autonomic activity using spectral analysis of heart rate variability and echocardiography in 31 normal women. The heart rate variability was calculated from 24-hour ambulatory electrocardiogram by Fourier transformation. The power spectra were quantified at 0.04-0.15 Hz (low frequency power (LF) 1n (ms2)) and 0.15-0.40 Hz (high frequency power (HF) 1n (ms2)). The HF component and the ratio of LF/HF were used as indices of parasympathetic and sympathetic activity, respectively. MVP was present in 22.6%. There were no significant differences in left ventricular dimension between subjects with MVP (group MVP (+)) and subjects without MVP (group MVP(-)). Number of ventricular premature contractions in group MVP(+) tend to be higher compared with that in group MVP(-). The level of high frequency power at 0-5 am in group MVP(+) was significantly higher than that in group MVP(-), which parasympathetic activity during sleep in MVP(+) group was higher compared with that in group MVP(-). The evaluation of autonomic activity using spectral analysis of heart rate variability for 24-hour ambulatory electrocardiogram might provide useful information about the pathology of MVP.

Adult↗
PubMed1996

Chiral separation of 10,11-dihydro-10, 11-trans-dihydroxycarbamazepine, a metabolite of carbamazepine with two asymmetric carbons, in human serum.

Chiral separation of 10, 11-dihydro-10, 11-trans-dihydroxycarbamazepine (CBZ-diol), a metabolite of carbamazepine (CBZ) with two asymmetric carbons, in serum taken from epileptic patients receiving CBZ alone for a long period, was performed by high-performance liquid chromatography using a polysaccharide stationary phase with n-hexane-ethanol (75:25, v/v) as the mobile phase. The enantiomeric ratio (S,S-/R,R-CBZ-diol) was 10.74 +/- 1.13 (mean +/- S.D.), which could demonstrate the presence of the stereospecificity in the hydrolysis of 10, 11-dihydro-10, 11-epoxycarbamazepine (CBZ-epoxide) to CBZ-diol and/or in the conversion of CBZ-diol to some metabolite such as 9-hydroxymethyl-10-carbamoylacridan. This is the first paper to report the determination of each enantiomer and the enantiomeric ratio of CBZ-diol in serum of epileptic patients who received CBZ.

Carbamazepine↗
PubMed1996

Determination of isonicotinic acid in the presence of isoniazid and acetylisoniazid. Studies on isonicotinic acid formation from isoniazid in isolated rat hepatocytes.

In comparison with the hepatocytes obtained from intact rats and rats pretreated with phenobarbital or 3-methylchoranthrene, the amount of isonicotinic acid (INA) formed from isoniazid (INH) increased substantially after incubation at 37 degrees C using the pretreated hepatocytes. This suggests an oxidative pathway for INA formation from INH, apart from hydrolysis. In order to explore the exact mechanism of INA formation in the hepatocytes, an HPLC assay for INA in the presence of INH and acetylisoniazid was developed. In this assay, INA was extracted after the preparation of an ion pair with tetra-n-butylammonium hydroxide, and analysed using an ODS column and a mobile phase consisting of 0.067 M potassium dihydrogenphosphate solution-methanol (96:4, v/v). The method is simple, accurate and especially suitable for INA determination after incubation of INH in isolated rat hepatocytes.

Animals↗
PubMed1996

Sites and types of UV-induced mutations leading to inactivation of the growth-arresting activity in p21 (sdi1/cip1/waf1) cDNA.

The p53-regulated gene product p21 (sdi1,cip1,waf1) negatively regulates cell growth and has been suggested to be a potential tumour-suppressor gene. To determine the sites and types of mutations which inactivate the growth-arresting activity in sdi1 cDNA, plasmids containing sdi1 cDNA and the neomycin-resistant gene were irradiated with UV light and transfected into CHO cells. The UV irradiation increased number of the geneticin-resistant colonies which should have the UV-mutated sdi1 cDNA. Sdi1 mRNA was expressed in 23 out of 36 colonies (64%). In 13 sdi1 cDNA sequences analysed, mutations were found at codon 46 in nine cDNAs, and one each at codons 34, 54, 66 and 73. All the mutation sites are in the CDK-binding region. Ten mutations (77%) (codons 46 and 66) are C to T transition mutation at the dipyrimidine sequences, which is the major type of the UV-induced mutation.

Animals↗
PubMed1996

Does the cell wall skeleton from Bacille Calmette-Guérin directly induce interferon-gamma, independent of interleukin-12?

Interleukin-12 (IL-12), known to be a strong inducer of interferon-gamma (IFN-gamma), plays a vital role in activating the immune surveillance system against intracellular pathogens and malignant tumors. The authors have found that cancer patients showing marked IFN-gamma induction after inoculation with BCG-CWS (the cell wall skeleton from Bacille Calmette-Guérin) have a good prognosis. The present study was undertaken to determine whether the level of IL-12 is increased prior to, or along with, IFN-gamma induction in the serum of patients inoculated with BCG-CWS. Unexpectedly, we found no detectable amount of IL-12 in the serum throughout the entire time course. This suggests that a novel IFN-gamma inducing factor (IGIF) or another unknown IFN-gamma inducer may be working in place of IL-12 in the BCG-CWS system.

Adjuvants, Immunologic↗
PubMed1996

Pancreatic calculi superimposed upon slow growing pancreatic cancer.

We report on a 59 year old male patient with cancer of the head of the pancreas, upon which pancreatic calculi were superimposed during the 3 year clinical course. Pancreatic calculi were noted in the main pancreatic duct (MPD) on both computed tomographic scans and ultrasonographs of the abdomen approximately 10 months after the recognizable dilatation of the MPD. Existence of the calculi was confirmed by autopsy. Elemental analysis and infrared spectrophotometry of the calculi demonstrated that the main constituent of the calculi was calcium carbonate. Histopathological examination showed that the pancreatic cancer was moderately differentiated adenocarcinoma. Immunohistochemical studies revealed that pancreatic stone protein (lithostathine) was present in the cytoplasm of tumour cells. In this case, pancreatic cancer progressed to obstruct the MPD unusually slowly, resulting in stagnation of pancreatic secretion and subsequent formation of the calculi.

Adenocarcinoma↗