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Biomedical subjects

K Harada

Publications and source records attributed to K Harada.

At least 793 records · Page 44Linked to original sources

Foam counter-current chromatography of bacitracin. II. Continuous removal and concentration of hydrophobic components with nitrogen gas and distilled water free of surfactants or other additives.

Foam counter-current chromatography has been successfully applied to continuous removal and concentration of hydrophobic bacitracin (BC) components from a large volume solution using nitrogen gas and distilled water free of surfactants or other additives. The experiment was initiated by introducing nitrogen at the head inlet of the coil rotated at 500 rpm. Then, a 2.5-1 volume of the sample solution containing BC at 50 ppm was continuously introduced into the middle portion of the coil at 1.5 ml/min. The hydrophobic components produced a thick foam which was carried with the gas phase and collected from the tail end of the coil while other components stayed in the liquid stream and eluted from the head outlet of the coil. High-performance liquid chromatographic analysis of the foam fraction revealed that the degree of enrichment increased with hydrophobicity of the BC components. BC-A and -F were enriched 1400 and 2260 times, respectively, compared with the original concentration in the sample solution. These results clearly indicate that the present method will be quite effective for detection and/or isolation of a small amount of natural products present in a large volume of aqueous solution.

Bacitracin↗

The effect of diltiazem on hepatic drug oxidation assessed by antipyrine and trimethadione.

The effect of pretreatment for 3 days with diltiazem 60 mg three times a day on the pharmacokinetics of 500-mg antipyrine and 250-mg trimethadione was studied in six healthy male subjects. Diltiazem decreased the total body clearance from 34.0 +/- 8.0 to 28.6 +/- 6.1 mL/min (P less than .01), and prolonged the elimination half-life from 12.6 +/- 3.0 to 14.3 +/- 2.5 hours (P less than .01) of antipyrine without any changes in volume of distribution. The cumulative renal excretion (% dose) of antipyrine was significantly increased from 2.23 +/- 0.73 to 2.78 +/- 0.83% (P less than .05). Clearances of production for three major antipyrine metabolites, norantipyrine (4.31 +/- 1.64 to 3.50 +/- 1.28 mL/min, P less than .01), 3-hydroxymethylantipyrine (4.67 +/- 1.63 to 3.82 +/- 1.34 mL/min, P less than .01) and 4-hydroxyantipyrine (10.47 +/- 3.41 to 8.16 +/- 2.82 mL/min, P less than .01) were reduced significantly by diltiazem. On the other hand, diltiazem did not produce any significant changes in pharmacokinetic parameters of trimethadione and plasma concentration ratio, oxidative major metabolite of trimethadione to trimethadione itself. These results suggest that other drugs metabolizing the same hepatic oxidative pathways as antipyrine, may be influenced by diltiazem.

Adult↗

Modified epiphyseal index for MRI in Legg-Calve-Perthes disease (LCPD).

On radiographs flattening of the femoral head is evaluated by the Epiphyseal Index (EI). Using the ability of MRI to show articular cartilage and the physis clearly, we wish to propose the use of an Epiphyseal Index for MRI (EIM) and demonstrate the value in LCPD. Fifteen patients were examined using 1.5T MR scanner and T1-weighted coronal images were obtained. EIM was calculated as a ratio of height and width of cartilaginous contour surrounding epiphysis, and was compared between normal and the three radiographic stages. EIM of normal hips were ranged from 0.39 to 0.60 and had a tendency to decrease with increasing age. All cases of Stage 1 (avascular necrosis) were within the normal range (n = 4, mean = 0.51, SD = 0.045). EIM of Stage 2 (fragmentation, n = 15, mean = 0.31, SD = 0.055) were smaller than that of Stage 1. Stag 2 and 3 (residual, n = 12, mean = 0.31, SD = 0.077) could not be distinguished by EIM. EIM was useful to show the flattening of epiphysis with growth and very important for differentiation between Stage 1 and 2 LCPD.

Adolescent↗

The cyclization of arabinosyladenine-5'-phosphorimidazolide.

When arabinosyladenine-5'-phosphorimidazolide is allowed to decompose in aqueous solution at room temperature and pH 7.2, depending on the buffer, 5-24% is converted to the 2',5'-cyclic phosphate (V). Although the extent of cyclization is much greater than for adenosine-5'-phosphorimidazolide, cyclization is less efficient than hydrolysis and so would not substantially decrease the efficiency of condensation reactions in aqueous solution. The significance of this result for prebiotic chemistry is discussed.

Adenosine Monophosphate↗

Coronal reconstruction images of glucose metabolism in Alzheimer's disease.

Coronal images of position emission tomography (PET) by 18F-labelled deoxyglucose reconstructed from interpolated scan in Alzheimer's disease clearly indicated suppression of glucose metabolism in the parietal lobe and lateral part of the temporal lobes, compared to normal controls. The medial part of the temporal lobes in Alzheimer's disease did show a mildly lower glucose metabolic rate than that in normal controls; therefore it is suggested that the parietal and lateral parts of the temporal lobes are primary affected regions in Alzheimer's disease, not the medial part of the temporal lobe, including the hippocampus.

Adult↗

Isolation of two toxic heptapeptide microcystins from an axenic strain of Microcystis aeruginosa, K-139.

Two toxic heptapeptides were isolated from an axenic Microcystis aeruginosa strain, K-139. Using mainly a non-destructive NMR method, we determined the structure of the major toxin to be 7-desmethylmicrocystin LR which lacks an N-methyl group of the dehydroalanine moiety of microcystin LR. The minor toxin was deduced to be 3,7-didesmethylmicrocystin LR. The chromatographic and NMR analyses of 7-desmethylmicrocystin LR were compared with those of 3-desmethylmicrocystin LR.

Amino Acid Sequence↗

Inhibitory effects of a novel PAF antagonist E6123 on anaphylactic responses in passively and actively sensitized guinea pigs and passively sensitized mice.

The effects of the platelet-activating factor (PAF) antagonist, E6123, on anaphylactic responses in guinea pigs and mice were investigated. E6123 inhibited i.v. antigen (Ag)- or inhaled Ag-induced bronchoconstriction in passively and actively sensitized guinea pigs after oral administration at 3 and 10 micrograms/kg, respectively. E6123 inhibited Ag inhalation-induced airway hyperreactivity in guinea pigs after oral administration at 30 micrograms/kg. E6123 protected mice from anaphylactic death with an ED50 value (p.o.) of 7 micrograms/kg. The inhibitory effects of E6123 described above were very potent compared to those of the PAF-antagonists WEB2347 and Y-24180. The present results suggest that E6123 may be beneficial for the treatment of asthma, a condition in which PAF is assumed to be involved.

Administration, Inhalation↗

A method for detecting effect of beneficial mutations in natural populations of Drosophila melanogaster.

An experimental method is proposed for detecting the effects of positive natural selection on DNA polymorphisms. Since beneficial mutations are expected to increase in frequency faster than neutral mutations, variants which have reached high frequencies in a relatively short period could be linked to some beneficial mutation. D. melanogaster has a cosmopolitan polymorphic inversion -In(2L)t- whose age in some local populations has been estimated. Setting the age of In(2L)t as the upper limit for the age of variants, we searched for variants whose frequencies were possibly influenced by positive natural selection. We detected a single candidate whose frequency and distribution met the requirements imposed by our method.

Alleles↗

Intracellular cAMP regulates the response to NMDA in hippocampal neurons.

We have studied the effects of intracellular cyclic AMP (cAMP) on the response to N-methyl-D-aspartate (NMDA) in hippocampal cultured neurons by loading them with 2'-o-dibutyryladenosine 3', 5'-cyclic monophosphate (dcAMP) and have obtained evidence for regulation of Ca2+ release from intracellular stores by cAMP. Extracellular Ringer's solution was either Ca(2+)-containing or Ca(2+)-free. A brief initial stimulation with NMDA (10-100 microM, 12 s) was required before the neurons were loaded with dcAMP to potentiate the changes in intracellular Ca2+ concentration induced by the second stimulus of NMDA. Forskolin (10 microM) mimicked dcAMP, but to a lesser extent. A phorbol ester 12-o-tetradecanoylphorbol-13-acetate (100 nM) inhibited the effect of dcAMP.

Animals↗

Development of macromolecular Sn(II) complex for preparation of 99Tcm radiopharmaceuticals.

Macromolecular Sn(II) complex (R-Sn) was developed using a chelating resin containing aminophosphonic acid groups as a reducing agent of 99Tcm(VII) in the preparation of 99Tcm radiopharmaceuticals. Since Sn(II) was bonded strongly to the resin by chelation, release of Sn from R-Sn was rarely observed in saline solution. 99Tcm labelling with a yield greater than 90% was performed by mixing R-Sn, 99Tcm pertechnetate solution and a ligand, such as human serum albumin and diethylenetriamine pentaacetic acid, for a short time. The 99Tcm radiopharmaceuticals were almost free from Sn(II) and the reducing activity of R-Sn was quite stable despite long-term storage without any special care.

Adsorption↗

Structure-function relationships of microcystins, liver tumor promoters, in interaction with protein phosphatase.

Microcystins, isolated from toxic blue-green algae, are potent inhibitors of protein phosphatases 1 and 2A. Recently, we have reported that microcystin LR has a potent tumor-promoting activity on rat liver initiated with diethylnitrosamine. The structure of microcystins is unique in having an unusual amino acid, 3-amino-9-methoxy-10-phenyl-2,6,8-trimethyl-deca-4(E),6(E)-dienoic acid (Adda), which is thought to be significant for the activity. Geometrical isomers at C-7 in the Adda portion of microcystins, 6(Z)-Adda microcystins LR and RR, have been isolated from cyanobacteria. To estimate their tumor-promoting activities and to understand the importance of the Adda portion for activity, the maternal microcystins LR and RR and their isomers were subjected to examination of their interaction with protein phosphatases 1 and 2A and the release of glutamic pyruvic transaminase from rat liver. 6(Z)-Adda microcystins LR and RR bound to protein phosphatases 1 and 2A, inhibited their activities and released glutamic pyruvic transaminase from rat liver into serum, ten to one hundred times more weakly than the maternal microcystins LR and RR. These results indicated that the conjugated diene with 4(E),6(E) geometry in the Adda portion is important in the interaction with protein phosphatases.

Alanine Transaminase↗

Intravenous gamma-globulin treatment in Kawasaki disease.

A multicenter randomized controlled study was carried out to assess the effectiveness of different, doses and kinds of gamma-globulin in Kawasaki disease. Gamma globulin lowered the incidence of coronary artery abnormalities. The effect of gamma-globulin was dose dependent. The intact type was more effective than the pepsin treated type. To establish the indications for gamma-globulin, a study was made of patients who received neither gamma-globulin nor indomethacin and who, within nine days of onset of illness, satisfied at least four of the following criteria: (1) WBC: more than 12,000/mm; (2) platelet count: less than 35 X 10(4)/mm; (3) CRP: more than 3+; (4) Hct: less than 35%; (5) albumin: less than 3.5 g/dl (6) age: 12 months or less; (7) male sex. This prospective study is continuing. Of 143 children, 73.4% received gamma-globulin, and only two demonstrated small dilatations of the coronary arteries in children who did not receive gamma-globulin. These guidelines seem satisfactory to establish the indications for gamma-globulin in Kawasaki disease.

Aspirin↗

Memory loss due to transient hypoperfusion in the medial temporal lobes including hippocampus.

A typical case of transient global amnesia (TGA) was investigated with single photon emission computed tomography (SPECT) and magnetic resonance imaging (MRI) with 1.5-tesler scans. During the amnesic episode, a marked decrease of cerebral blood flow was observed in the areas confined to the territory of the bilateral posterior cerebral arteries including the hippocampus. After the episode, cerebral blood flow returned to normal and a circumscribed lesion was detected in the middle portion of CA 1 field of the left hippocampus. The SPECT findings prove direct evidence that the medial temporal structures are involved in the establishment of new memories, as well as in process of recalling only recently acquired memories, but not in retrieval of memories acquired long ago. The MRI findings indicate that a unilateral partial damage to CA 1 sector of the hippocampus does not develop a definite memory impairment and that high-resolution MRI study on the hippocampus is necessary in TGA patients.

Amnesia↗

Herpes simplex virus type 1 and type 2 infection in human oral mucosa in culture.

To examine the sensitivity of human oral mucosa to herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) infection, human gingival mucosa explants were infected with either HSV-1 or HSV-2 in vitro and the expression of virus specific antigen was examined by the immunofluorescent antibody technique. HSV-2 antigen was found in the basement membrane, basal cell layer and lower prickle cell layer. This finding was consistent with the HSV-1 infection. Electron microscopic study revealed the presence of nucleocapsids and enveloped virus particles in the basal cells of HSV-2-infected organ cultures. These findings indicate that human gingival mucosa is sensitive to infection with HSV-2, as well as HSV-1, and that the virus may replicate in the undifferentiated epithelial cells of mucosal epithelium.

Adolescent↗

[Serotype and antibiotic susceptibilities of group A hemolytic streptococci isolated in Osaka, 1988-1989].

A total of 386 strains of Group A hemolytic Streptococci isolated from the patients in Osaka in 1988 and 1989 were type-classified by both T-agglutination and M-precipitin methods and were examined for drug-sensitivity. The results were summarized as follows. 1. From T-typing result, T-1 (28.2%) was revealed as the most dominant serotype in 1988, followed by T-4 (24.9%), and T-12 (23.2%), although not as much difference was found in the isolation rate among these three types. A similar tendency was observed in the results of 1989. The order was T-4 (30.3%), T-1 (24.8%), and T-12 (22.1%). 2. In the isolated Group A hemolytic Streptococci, 177 out of 241 strains (73.4%) in 1988 and 126 out of 145 strains (86.9%) in 1989 were M-typable with seven kinds of M-typing sera (Anti-M-1, 3, 4, 6, 12, 13, 18). The result of M-typing was similar to that of T-typing, because the coincidence rate between T and M types was very high among the most prevalent serotypes such as 1, 4, 6, and 12 (type-1: 98.1%, type-4:89.4%, type-6:91.7%, type-12:94.3%). 3. The number of antibiotic-resistant strains decreased. It was especially prominent in the resistant strains to erythromycin, lincomycin and chloramphenicol. While the incidence of tetracycline resistant strains in type-4, 11 and 13 remained at a high level, it decreased in type-12 and 1. All strains were sensitive to the beta-lactam antibiotics. 4. No resistant strains were detected to enoxacin (ENX) and ofloxacin (OFLX), new quinolone. MIC90 values of ENX and OFLX were 16 micrograms/ml and 2 micrograms/ml, respectively, although difference of MIC90 was observed among some strain types: MIC90 of ENX against type-6 strain was 8 times higher than that against type-12 strain.

Anti-Bacterial Agents↗

Toxicity and toxins of natural blooms and isolated strains of Microcystis spp. (Cyanobacteria) and improved procedure for purification of cultures.

All samples of cyanobacterial blooms collected from 1986 to 1989 from Lake Kasumigaura, Ibaraki Prefecture, Japan, were hepatotoxic. The 50% lethal doses (LD50s) of the blooms to mice ranged from 76 to 556 mg/kg of body weight. Sixty-eight Microcystis cell clones (67 Microcystis aeruginosa and 1 M. viridis) were isolated from the blooms. Twenty-three strains (including the M. viridis strain) were toxic. However, the ratio of toxic to nontoxic strains among the blooms varied (6 to 86%). Microcystins were examined in six toxic strains. Five toxic strains produced microcystin-RR, -YR, and -LR, with RR being the dominant toxin in these strains. Another strain produced 7-desmethylmicrocystin-LR and an unknown microcystin. This strain showed the highest toxicity. Establishment of axenic strains from the Microcystis cells exhibiting extracellularly mucilaginous materials was successful by using a combination of the agar plate technique and two-step centrifugation.

Animals↗

Colonic mucosal interleukin-6 in inflammatory bowel disease.

Interleukin-6, a cytokine produced by various cell types, has a major role in inflammatory and immunological reactions. To define its potential role in inflammatory bowel disease, its concentrations in endoscopic biopsy samples from patients with ulcerative colitis and Crohn's disease were measured. The involved colonic mucosa from active disease was found to contain significantly larger amounts of interleukin-6 than that from inactive disease or normal controls. Colonic mucosal interleukin-6 levels correlated well with the grade of macroscopic inflammation, especially in patients with ulcerative colitis. The levels of interleukin-6 decreased in parallel with clinical improvement following the start of therapy in patients with both forms of inflammatory bowel disease. Mucosal interleukin-6 is thus concluded to accurately reflect the degree of colonic inflammation and may be importantly associated with inflammatory and immunological phenomena seen in inflammatory bowel disease.

Adult↗

Dissolution and bioavailability of phenobarbital in solid dispersion with phosphatidylcholine.

The dissolution of phenobarbital (PB) from solid dispersion with phosphatidylcholine (PC) was studied. PB was present in an amorphous state in solid dispersion (PB-PC) if the mole fraction of PB was under 0.75. Thus, supersaturation was observed when an excess amount of PB-PC was dispersed in pH 1.2 and 6.8 media. The degree of supersaturation was largest when the mole fraction of PB was 0.25, although it was only 1.3-fold of the PB solubility in this case. Dissolution from PB-PC was rapid and complete in both pH 1.2 and 6.8 media regardless of the mole fraction of PB, above 90% within 5 min. Bioavailability after the oral administration of PB-PC to rabbits with a dose of 15 mg/kg equivalent to PB was compared with that of PB crystals. The area under the plasma concentration curve was bigger, but not significant. The maximum concentration was significantly higher, and the time to maximum concentration was significantly faster. These results indicate that the absorption rate became high with PB-PC because the dissolution was rapid.

Animals↗