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Biomedical subjects

H Nishi

Publications and source records attributed to H Nishi.

At least 109 records · Page 6Linked to original sources
PubMed1992

Genetic analysis of dilated cardiomyopathy--HLA and immunoglobulin genes may confer susceptibility.

To identify genetic factors in the immune system which control the susceptibility to dilated cardiomyopathy (DCM), HLA class II DNA typing was performed in 61 Japanese patients, using PCR/SSO probe analyses. The frequencies of HLA-DQB1*0503 (15% vs 5%; RR = 3.06, chi 2 = 7.19) and DQB1*0604 (21% vs 10%; RR = 2.41, chi 2 = 6.20) were significantly increased and that of HLA-DQB1*0502 (RR = 1.74) was slightly increased in the DCM patients. The frequency of DQB1*0303 (16% vs 31%; RR = 0.44, chi 2 = 5.16) was significantly decreased in the patients. The increased HLA-DQB1 alleles have a histidine residue in common at the 30th codon for the HLA-DQ beta chain. Among the genetic markers studied by Southern blot analyses, IGLV (immunoglobulin lambda light chain, pV3.3) showed a strong association with DCM, i.e. A2/A2 genotype was found in 37.7% of patients whereas it was observed in only 18.9% of the control subjects (RR = 2.6, chi 2 = 7.77). The frequency of this genotype was higher in patients under age 45 years at the time of diagnosis (45.5%, RR = 3.6, chi 2 = 10.02). These results suggest that HLA and immunoglobulin genes are closely linked to susceptibility to DCM.

Adolescent↗
PubMed1992

Nucleotide sequence of the third cytokine LD78 gene and mapping of all three LD78 gene loci to human chromosome 17.

Cytokine LD78 is a member of a newly identified cytokine superfamily. We cloned the third human gene for the LD78, termed LD78 gamma and the sequence analysis showed that it is a 5'-truncated pseudogene. Exons 2 and 3 and the intron between them are highly homologous to those of the LD78 beta gene, hence, the gamma gene was probably derived from the beta gene. Southern blot analysis of human x mouse somatic hybrid cell DNAs and in situ hybridization experiments mapped all the three gene loci on human chromosome 17q21.1-q21.3. Analysis of DNAs from family members supports our previous finding that the beta and gamma genes on each of the paired chromosome 17 vary in copy number and that the LD78 alpha gene is presumably a single copy. In our analyses of cosmid clones, the LD78 beta gene and the second gene for AT744, which is also a member of the superfamily are closely linked in a head-to-head arrangement. The mechanism of generation of the three LD78 genes is discussed.

Base Sequence↗
PubMed1992

[Pharmacokinetic, bacteriological and clinical studies on cefprozil in pediatric patients].

Cefprozil (CFPZ, BMY-28100), a new oral cephem antibiotic, was studied for its antibacterial activities, absorption and excretion upon administration. Its clinical efficacies were also studied in pediatric patients with infections. A study on antibacterial activities of CFPZ against 11 clinical isolates including 6 species found that its activities against Staphylococcus aureus, alpha-hemolytic Streptococcus, Escherichia coli and Haemophilus influenzae were equal or superior to those of CCL. When CFPZ was given to patients orally at 15 mg/kg, maximum serum concentration was obtained between 1 to 2 hours after administration and urinary excretion rate in the first 6 hours was 33.8 +/- 17.6%. Clinical evaluation was done in a total of 25 patients with various infections. Responses were excellent in 15 cases and good in 10 cases, hence the efficacy rate was 100%. As side effect, soft stool was found in 1 case, and eosinophilia in 2 cases and elevation of GOT and GPT in 1 case were found as abnormal laboratory test results, but none of them was serious. It appears that CFPZ is an effective and safe antibiotic in the field of pediatrics.

Bacteria↗
PubMed1991

[Pharmacokinetic and clinical evaluations of flomoxef in neonates].

To evaluate pharmacokinetics and clinical efficacy of flomoxef (6315-S, FMOX) in neonates, FMOX was administered to 21 neonates. With 20 mg/kg and 40 mg/kg of intravenous drip-infusion of FMOX 60 minutes, half lives (T 1/2's) was 64.9 minutes and 130.3 minutes, respectively, and when 20 mg/kg of FMOX was infused intravenously to 2 cases, half lives were 70.8 minutes and 110.1 minutes, respectively. When 45-100 mg/kg of FMOX was administered to 17 neonates with infections (pneumonia 8, sepsis 1, sepsis suspected 2, intrauterine infection 2, urinary tract infection 2, omphalitis 2), the efficacy rate was 88.2% (15 of 17). No adverse reactions were observed clinically in the 21 neonates. Transient elevation of eosinophilia was observed in 1 case and transient elevation of S-GOT and S-GPT 1 in another. These results suggest that FMOX is an effective and safe antibiotic to use in neonates.

Alanine Transaminase↗
PubMed1991

A new monoclonal antibody directed to sialyl alpha 2-3lactoneotetraosylceramide and its application for detection of human gastrointestinal neoplasms.

A new monoclonal antibody (NS24) directed to the N-acetylneuraminyl alpha 2-3Gal beta 1-4GlcNAc residue in type II sugar chain of N-acetylneuraminyllactoneotetraosylceramide [sialylparagloboside, IV3(NeuAc)nLc4Cer] was prepared by hybridoma technique. Liposomes composed of dipalmitoylphosphatidylcholine, cholesterol, IV3(NeuAc)nLc4Cer, and lipopolysaccharides from Salmonella minnesota R595 were used for immunization with IV3(NeuAc)nLc4Cer isolated from human erythrocytes. This method allowed the fusion of spleen cells of immunized mouse with myeloma cells only three days after immunization. NS24 reacted specifically to both naturally occurring and chemically synthesized IV3-(NeuAc)nLc4Cer, whereas it has no reactivity to structurally related gangliosides, such as IV6(NeuAc)nLc4Cer, N-glycolylneuraminyl alpha 2-3lactoneotetraosylceramide [IV3(NeuGc)-nLc4Cer], i-active ganglioside [VI3(NeuAc)nLc6Cer], I-active ganglioside [VIII3(NeuAc)-VI3(NeuAc)IV6kladoLc8Cer], GM4(NeuAc), GM3(NeuAc), GM3(NeuGc), GM1b(NeuAc), GD3-(NeuAc), other ganglio-series gangliosides, sulfatide, and paragloboside (nLc4Cer). Synthetic N-acetylneuraminyl alpha 2-3lactotetraosylceramide [IV3(NeuAc)Lc4Cer] and its asialo-derivative (Lc4Cer) carrying type I sugar chain also showed no reaction with NS24. One to 100 pmol of IV3(NeuAc)nLc4Cer was detected dose-dependently by a thin-layer chromatography/enzyme immunostaining procedure. Human gastric carcinomas showed positive reactions with NS24 immunochemically and histochemically. NS24 reacted preferentially with poorly differentiated adenocarcinomas rather than well differentiated ones.

Adenocarcinoma↗
PubMed1990

Chiral separation of diltiazem, trimetoquinol and related compounds by micellar electrokinetic chromatography with bile salts.

The separation of optically isomeric diltiazem hydrochloride, trimetoquinol hydrochloride and related compounds by micellar electrokinetic chromatography was investigated employing four bile salts as chiral surfactants. The chiral separation of diltiazem hydrochloride and timetoquinol hydrochloride was successfully achieved by use of sodium taurodeoxycholate under neutral conditions, although enantiomers of carboline derivatives A and B and 2,2'-dihydroxy-1,1'-dinaphthyl were resolved with all the bile salts under conditions from neutral to alkaline. The chiral separation of diltiazem-related compounds was affected by the structure of the samples in addition to the effects of bile salt structures and pH of the buffer solutions. Application to the optical purity testing of trimetoquinol hydrochloride by the area percentage method is described. A possible chiral separation mechanism is briefly mentioned.

Bile Acids and Salts↗
PubMed1990

Separation and determination of aspoxicillin in human plasma by micellar electrokinetic chromatography with direct sample injection.

Both the separation and determination of aspoxicillin in human plasma by micellar electrokinetic chromatography (MEKC) were investigated. Selectivity in the separation of seven penicillin antibiotics was improved by using MEKC in comparison with capillary zone electrophoresis. Plasma proteins, which might interfere with drug analysis in conventional chromatography, were solubilized by the micelles employed in MEKC and eluted later than the drugs. This permitted the determination of the drugs in plasma by a direct sample injection method. One analysis of a plasma sample was performed within ca. 20 min without pretreatment. Good linearity and recovery were also obtained in the range of plasma levels usually encountered in clinical analysis with a correlation coefficient r = 0.999 and 94-104% recovery. The limit of detection for aspoxicillin was 1.3 micrograms ml-1 at a signal-to-noise ratio of 3.

Amoxicillin↗
PubMed1990

Separation and determination of lipophilic corticosteroids and benzothiazepin analogues by micellar electrokinetic chromatography using bile salts.

The separation of corticosteroids and benzothiazepin analogues by micellar electrokinetic chromatography (micellar EKC) was studied in comparison with capillary zone electrophoresis. The separation of these substances was not successful under neutral and alkaline conditions because they migrated with the same velocity as that of the electroosmotic flow. Micellar EKC with sodium dodecyl sulphate (SDS) solutions was also not successful because these substances migrated with almost the same velocity as that of the SDS micelle, owing to their high lipophilicity. The use of bile salts, which have a similar skeleton to corticosteroids, as the micellar phase permitted the separation of these substances with high theoretical plate numbers (150,000-350,000) within a short time (ca. 15 min). Sodium cholate was particularly useful. The effects of bile salt concentration, pH and the addition of methanol were investigated. Micellar EKC was also applied to the determination of the drug substances in tablets and cream using the internal standard method and to purity testing of drug substances and tablets.

Adrenal Cortex Hormones↗
PubMed1990

Separation and determination of the ingredients of a cold medicine by micellar electrokinetic chromatography with bile salts.

The separation of fourteen active ingredients used in a cold medicine was investigated by micellar electrokinetic chromatography (EKC) employing bile salts. Basic drugs were also successfully separated by micellar EKC using bile salts with high theoretical plate numbers (2.0 x 10(5)-3.5 x 10(5)) within a relatively short time (ca. 20 min). The separation of these solutes by micellar EKC was not successful using sodium dodecyl sulphate. The effects of micellar concentration, pH and organic modifier content on migration times and selectivity were investigated. This technique was also applied to the determination of several active ingredients combined in commercial preparations by an internal standard method.

Acetaminophen↗
PubMed1990

Application of micellar electrokinetic chromatography to pharmaceutical analysis.

Electrokinetic chromatography is a new type of analytical separation method which belongs to the group of high performance capillary electrophoretic techniques but whose separation principle is based on that of chromatography. The solute distributes itself between a carrier and the surrounding medium. The carrier, which corresponds to the stationary phase in conventional chromatography, can be transported by electrophoresis with a different velocity from the surrounding medium. The separation is achieved by the differential solute distribution and the differential migration of the carrier. The charged molecules or charged molecular aggregates are employed as the carrier. Various kinds of carriers are available for electrokinetic chromatography along with different partition mechanisms. Among them, micellar electrokinetic chromatography, which employs an ionic micelle as a carrier, has become the most popular method because of its unique and attractive characteristics as well as the separating capability of electrically neutral or nonionic solutes in comparison with capillary zone electrophoresis. The present paper describes the principle, separation characteristics and its application to the analysis of pharmaceuticals.

Chromatography↗
PubMed1990

Effect of surfactant structures on the separation of cold medicine ingredients by micellar electrokinetic chromatography.

Using micellar electrokinetic chromatography (micellar EKC or MEKC) the retention behavior of twelve active ingredients used in cold medicines was investigated. The role of five different anionic surfactants was investigated by MEKC and the results were compared with those obtained by conventional capillary zone electrophoresis (CZE). The relative retention order of the 12 ingredients was significantly different among the five surfactants; the different elution orders were ascribed to the differences in the hydrophilic groups of the surfactants. The effects of surfactant concentration and buffer pH were also investigated. The ingredients were successfully separated within 30 min by micellar EKC with high theoretical plate numbers (approximately 200,000), and selectivity was much improved in comparison with CZE. Micellar EKC was applied by the internal standard method to the quantitation of some active ingredients combined in commercial preparations.

Chemical Phenomena↗
PubMed1989

Separation of beta-lactam antibiotics by micellar electrokinetic chromatography.

The retention behaviour of beta-lactam antibiotics in micellar electrokinetic chromatography (EKC) was investigated. Sodium dodecyl sulphate (SDS) and sodium N-lauroyl-N-methyltaurate were used an anionic surfactants at concentrations of 0.05-0.3 M. It was found that the retention of ionic substances in micellar EKC is determined by the following three factors: the electrophoretic migration of the ionic substances, the interaction between the ionic substances and ionic surfactants and solubilization of the solute by the micellar phase. A difference in the retention behaviours of cationic substances was observed between the two anionic surfactants, which have different groups neighbouring the charge-bearing groups. The effect of an ion-pairing reagent was also investigated to make the effect of the micelle clearer. All test solutes were successfully separated by micellar EKC at SDS concentrations above 0.1 M, with theoretical plate numbers ranging from 70,000 to 260,000.

Anti-Bacterial Agents↗
PubMed1989

Separation of water-soluble vitamins by micellar electrokinetic chromatography.

The retention behaviour of eleven water-soluble vitamins in micellar electrokinetic chromatography (micellar EKC) was investigated in comparison with capillary zone electrophoresis. Sodium dodecyl sulphate (SDS) and sodium lauroylmethyl taurate were used as the anionic surfactants at concentrations of 0.05-0.2 M in micellar EKC. The retention times of cationic substances increased more rapidly with increasing concentration of the anionic surfactant than those of other substances. This result suggests that ion-pair formation between cationic substances and anionic surfactants contributes to the retention of the former. The difference in the structures of the two surfactants affects the retention behaviour of solutes, especially cationic substances. To clarify the effect of the micelle, an ion-pairing agent that does not form the micelle structure was employed. All solutes were successfully separated within 15 min by using a 650 mm x 0.05 mm I.D. fused-silica tube with a 0.05 M SDS solution (pH 9.0) to give theoretical plates ranging from 100,000 to 350,000.

Chemical Phenomena↗
PubMed1989

Effect of MCI-186 on ischemia-induced changes in monoamine metabolism in rat brain.

We examined the effects of MCI-186 (3-methyl-1-phenyl-2-pyrazolin-5-one), a novel free radical scavenger and an inhibitor of ischemia-induced brain edema, on monoamine metabolism in the brains of both normal and ischemic rats. In normal rats, 3 mg/kg i.v. MCI-186, a dose that prevents ischemic brain edema, had no significant effect on brain concentrations of dopamine, norepinephrine, 5-hydroxytryptamine, or their metabolites. After the injection of 5 microliters of 3% polyvinyl acetate into the left internal carotid artery, concentrations of 3,4-dihydroxyphenylacetic acid and homovanillic acid markedly increased, but that of norepinephrine decreased, in the left telencephalon of embolized rats compared with control rats injected with vehicle; the concentration of 5-hydroxyindoleacetic acid also increased slightly. These effects were maximal 2 hours after embolization. The turnover rate of dopamine between 6 and 8 hours after embolization was significantly higher but that of norepinephrine was slightly lower than that in vehicle-treated rats. When rats were treated with 3 mg/kg i.v. MCI-186 immediately after the injection of polyvinyl acetate, the embolization-induced changes in monoamine metabolism were less marked. Our results suggest that MCI-186 attenuates ischemia-induced changes in brain monoamine metabolism, probably due to its free radical scavenging action, although it has no marked effect in normal rats.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1989

Effect of MCI-186 on brain edema in rats.

We induced brain edema in 72 rats by injecting 5 microliters of 3.0% wt:vol polyvinyl acetate into the left internal carotid artery, producing permanent embolization in the left cerebral hemisphere, which developed ipsilateral brain edema reproducibly. Edema was assessed 24 hours after embolization by determining the brain water content and the sodium and potassium concentrations. In this model, the free radical scavenger MCI-186 at 1.0 and 3.0 mg/kg i.v. prevented brain edema in a dose-dependent manner. At 3.0 mg/kg i.v., MCI-186 significantly reduced water content by 1.5% and improved the sodium-potassium balance to within the normal range in the embolized left hemisphere. Dexamethasone at 1.0 mg/kg i.v. did but at 3.0 mg/kg i.v. did not significantly inhibit the development of brain edema. Indomethacin at 4.0 mg/kg i.p. had no effect on brain edema. We suggest that the cyclooxygenase metabolites of arachidonic acid liberated from neuronal cell membrane phospholipids are not likely to be involved in the pathogenesis of permanent brain edema induced by polyvinyl acetate. Our results suggest that MCI-186 attenuates brain edema by suppressing the production of lipoxygenase metabolites, including free radicals or lipid peroxides, and that it may prove valuable for the treatment of brain edema associated with cerebral ischemia.

Animals↗
PubMed1989

[Concentric left ventricular hypertrophy in patients with aortic regurgitation].

Chronic aortic regurgitation (AR) is a disease incorporating volume overload of the left ventricle (LV) which is characterized by hyperactive left ventricular dilatation (LVD). However, we have encountered several patients who had concentric LV hypertrophy (LVH) instead of LVD. We therefore studied 50 consecutive patients with isolated AR but without aortic stenosis and found seven patients with concentric LVH having LV wall thickness (determined by summing ventricular septal and posterior wall thicknesses) exceeding 30 mm and LV diastolic diameters of less than 60 mm. These seven patients with AR and LVH were older (55 +/- 27 vs 42 +/- 11 years) and tended to have milder degree of AR, compared with the remaining 43 patients having AR and LVD. However, patients with AR and LVH did not differ from AR and LVD as to the cardiothoracic ratio, SV1 + RV5, T-waves, ejection fraction, operative findings of valvular morphology and underlying etiologies. In contrast, patients with AR and LVH presented higher systolic (196 +/- 41 vs 149 +/- 26 mmHg, p less than 0.01) and diastolic pressures (74 +/- 14 vs 51 +/- 13 mmHg, p less than 0.01) and higher systemic vascular resistance (1,854 +/- 399 vs 1,388 +/- 352 dyne.sec.cm-5, p less than 0.05) during catheterization than did those with AR and LVD. However, blood pressure at the time of admission was not different in the two groups. These observations indicate that concentric LVH is not rare among patients with AR, and that an association of pressure overload with volume overload of the LV, particularly during exercise or stress, may lead to concentric LVH, even in patients with chronic AR.

Adult↗
PubMed1989

[Pharmacokinetic and clinical studies on sulbactam/ampicillin in the pediatric field].

The new antibiotic, sulbactam/ampicillin (SBT/ABPC) was administered to 25 children. The results obtained are summarized as follows. 1. In 5 cases of children administered with SBT/ABPC (30 mg/kg) by intravenous drip infusion for 30 minutes, the mean values of T 1/2 (beta) were 0.94 hour (SBT) and 0.86 hour (ABPC) and the mean 6.5 hour urinary excretion rates were 64.2% and 42.9%, respectively. 2. The antibiotic was administered to a total of 25 patients with bronchopneumonia, pneumonia, bronchitis, cervical lymphadenitis, tonsillitis, streptococcal infection, urinary tract infection, felon, periappendicular abscess, sepsis or purulent meningitis. Response to the treatment were excellent in 17 cases, good in 7, fair in 1, and poor in none. The efficacy rate was 96%. From our results, this drug appears to be particularly effective against bronchopneumonia, bronchitis and urinary tract infection. 3. Eruption occurred in 1 of 25 patients and elevation of eosinophil, GOT/GPT, platelet in 3 and descent of WBC in 1 were observed, but these were transient. These results showed that SBT/ABPC is a drug which can be safely used in the pediatric field as well as for adults.

Age Factors↗