Biomedical subjects

T Ohta

Publications and source records attributed to T Ohta.

At least 469 records · Page 26Linked to original sources

PubMed1997

Specific CYP3A4 inhibitors in grapefruit juice: furocoumarin dimers as components of drug interaction.

Four components were isolated from grapefruit juice that inhibit human CYP3A-mediated drug oxidation. The structures of these compounds were identified as furocoumarin derivatives by absorption spectra, APCI-liquid chromatography/tandem mass spectrometry and nuclear magnetic resonance after their purification by reversed-phase high performance liquid chromatography. They include two new furocoumarins, 4-[[6-hydroxy-7-[[1-[(1-hydroxy-1-methyl)ethyl]-4-methyl-6- (7-oxo-7H-furo[3,2-g][1]benzopyran-4-yl)-4-hexenyl]oxy]-3,7-dimeth yl- 2-octenyl] oxy]-7H-furo[3,2-g][1]benzopyran-7-one (GF-I-1) and 4-[[6-hydroxy-7-[[4-methyl-I- (1-methylethenyl)-6-(7-oxo-7H-furo[3,2-g][1]benzopyran-4-yl)-4- hexenyl] oxy]-3,7-dimethyl-2-octenyl]oxy]-7H-furo[3,2-g][1]benzopyran-7-one (GF-I-4). These furocoumarins are strong candidates for causative agents of grapefruit juice-mediated drug interaction, because of an inhibition potential that is equal to or stronger than the prototypical CYP3A4 inhibitor, ketoconazole, on liver microsomal testosterone 6 beta-hydroxylation.

Beverages↗

PubMed1997

Episodic evolution and turnover of HLA-B in the indigenous human populations of the Americas.

Nucleotide sequences were determined for the HLA-A, B and C alleles of three populations of Amerindians: the Havasupai tribe from North America, and the Guarani and Kaingang tribes from South America. All 15 Havasupai alleles are found in Eastern Hemisphere populations, whereas the Guarani and Kaingang each have six alleles that appear to be present only in the Western Hemisphere. Nine of the "new" alleles come from HLA-B, one comes from HLA-A and one from HLA-C: ten appear to be the result of recombination and one the result of point substitution. Of the 14 Guarani alleles and 16 Kaingang alleles, only four are held in common. Despite their differences, the three tribes possess comparable numbers of HLA class I alleles, revealing a trend for "allele turnover", in which new alleles tends to supplant older alleles rather than supplement them. Although many new HLA-B alleles have been produced in Latin America, their net effect has been to differentiate populations, not to increase allele diversity within a population. From sequence comparisons, the Amerindian subset of HLA class I allotypes appears to cover the overall ranges of peptide binding specificity, natural killer-cell interactions, and CD8 interactions, that are found in all HLA class I. The recombinations that produced the new alleles of the Kaingang and Guarani class I are predicted to have modulated these functional properties rather than radically change them. Exchange of Bw4 and Bw6 motifs by recombination are noticeably absent in the events forming new alleles in America, whereas they have been the most common of recombinations elsewhere.

Alleles↗

PubMed1997

Vitamin B12 treatment for delayed sleep phase syndrome: a multi-center double-blind study.

The active form of vitamin B12 (methylcobalamin) has been reported to be effective on sleep-wake rhythm disorders. Previous studies, however, were performed under open trial, and the effect of vitamin B12 has not been properly evaluated. The aim of this double-blind study was to investigate the efficacy of methylcobalamin on delayed sleep phase syndrome (DSPS). Methylcobalamin (3 mg/day) or placebo was administered for 4 weeks. The subjects were 50 patients with DSPS aged 13-55 years (26.8 +/- 1.3), 27 of whom received the active drug while 23 received the placebo. No significant differences were observed between the 2 groups in subjective evaluations of mood or drowsiness during the daytime or in night sleep by sleep-log evaluation. These results indicate that 3 mg methylcobalamin administered over 4 weeks is not an effective treatment for DSPS.

Adolescent↗

PubMed1997

Role of gene conversion in generating polymorphisms at major histocompatibility complex loci.

Multigene families are known to be evolving under continued occurrence of unequal crossing-over and gene conversion, and MHC loci are no exceptions. Population genetic models of diversifying selection, with intra- and inter-locus gene conversion were studied by computer simulations. Weak selection at individual amino acid site is shown to be quite effective in enhancing polymorphisms, if gene conversion occurs. This is caused by the appearance of coadapted segments of mutations in which recombination tends to be suppressed. In addition to the global type of diversifying selection, endemic type of selection was introduced in some sets of simulations to find out a mechanism of the rapid allelic turnover of South American Indians. Strong selection is assumed such that the most common two alleles become lethal in one generation. If this endemic selection occurs periodically, allelic turnover by intralocus gene conversion is shown to become rapid. Hence, interaction of selection and gene conversion has a profound effect on MHC polymorphisms.

Alleles↗

PubMed1997

[Usefulness of 7 day therapy with cefluprenam in the management of respiratory tract infections].

Efficacy and safety of a newer injectable cephalosporin, cefluprenam (CFLP) on cases with bacterial pneumonia and chronic respiratory tract infections were evaluated at a dose of 1g (potency), d.i.d for 7 days. 1. Of 130 cases in total, 116 cases were enrolled for the clinical efficacy evaluation. The efficacy rate (excellent and good responses) was 94.8% (110/116). The efficacy rate was 93.8% (60/64) for cases with bacterial pneumonia, and 96.2% (50/52) for cases with chronic respiratory tract infections. The recurrence was noted in 1.2% (1/82). The bacteriological response rate was 100.0% (32/32) for gram positive cocci, 93.8% (15/16) for gram negative rods and 97.9% (47/48) in total. 2. Adverse drug reactions were noted in 3.9% (5/129), consisting of 2 cases with skin rash, 1 case with drug fever, 1 case with skin rash and skin itching and 1 case with drug fever and headache. The abnormal laboratory changes were noted in 23.6% (30/127), mainly containing the elevation in GPT and GOT, and eosinophylia. The safety rate (no problem evaluation) was 74.8% (95/127). 3. The usefulness rate (very useful and useful evaluations) was 93.1% (108/116). As suggested by the evaluation on the secondary endpoint in the phase III comparative studies with both bacterial pneumonia and chronic respiratory tract infections, it was confirmed that the 7 day therapy of CFLP was promising for treatment of moderate bacterial pneumonia and chronic respiratory tract infections, because the high clinical efficacy was obtained and also the incidence of allergic reactions with CFLP was almost the same as that of ceftazidime (CAZ) evaluated highly safe. Based on these results, it was concluded that CFLP was useful in the management of moderate respiratory tract infections and also the recommended therapeutic period with CFLP was within 7 days.

Adult↗

PubMed1997

Early nonpolypoid colorectal cancer: radiographic diagnosis of depth of invasion.

PURPOSE: To diagnose depth of invasion of early flat and depressed nonpolypoid colorectal cancers with double-contrast barium enema examination. MATERIALS AND METHODS: Ninety-seven early nonpolypoid colorectal cancers, initially identified with colonoscopy, were investigated with double-contrast barium enema examination. Depth of invasion in resected specimens obtained with endoscopic mucosal or surgical resection was determined. Cancer confined to the mucosal layer or with focal extension to the submucosal layer was defined as Ca-m; moderate to massive extension of cancer into the submucosal layer was classified Ca-sm. RESULTS: In flat elevated and depressed cancers, converging folds and semilunar deformity were observed significantly more frequently in Ca-sm than in Ca-m tumors (P < .05 and P < .01, respectively). Sensitivities and specificities of these findings for Ca-sm tumor were 42%, 93% and 86%, 85%, respectively. Deep depression, irregular surface of the depression, and tumor size larger than 20 mm were also predictive findings for depressed Ca-sm tumors (P < .05); the specificity of each was 100%. With use of these radiographic predictors, overall accuracy for diagnosing depth of invasion was 85%. CONCLUSION: Findings on double-contrast barium enema study are highly predictive of depth of invasion of early nonpolypoid colorectal cancer. Radiographic findings of converging folds, semilunar deformity, deep depression, irregular surface of the depression, and tumor size are predictors of Ca-sm tumor.

Adult↗

PubMed1997

Three-dimensional spiral computed tomography angiography as an alternative imaging modality for a silent dissecting aortic aneurysm--a case report.

The authors report a patient with silent dissecting aortic aneurysm in whom three-dimensional spiral computed tomography (CT) angiography (3D-CTA) provided important imaging data. Images obtained by 3D-CTA were compared with the results of both conventional angiography and CT. They conclude that 3D-CTA was a powerful diagnostic modality for this patient, in addition to conventional CT and angiography.

Aortic Dissection↗

PubMed1997

Grapefruit component interacting with rat and human P450 CYP3A: possible involvement of non-flavonoid components in drug interaction.

Active components in grapefruit juice, which modulate a cytochrome P450 (CYP3A) activity, were investigated. CYP3A-catalyzed 6beta-hydroxylation of testosterone in livers of rat and human was inhibited by the addition of an ethyl acetate-extract of grapefruit juice. Several components of grapefruit juice, including naringin, naringenin, limonin and obacunone, also showed inhibitory effects in human liver microsomes. However, the amounts of these components in grapefruit juice are too low to account for the inhibition by the ethyl acetate-extracts. Analyses with HPLC indicate the existence of inhibitory components in the extract, which are distinct from these known compounds and are specific to grapefruit juice. These results suggest that hydrophobic components other than flavonoids, probably coumarin derivatives, are responsible for the inhibitory effect of grapefruit juice.

Animals↗

PubMed1997

[Chemiluminescent enzyme immunoassay of cholecystokinin in rat plasma using an immuno-affinity column as a pretreatment].

The cholecystokinin (CCK) plasma concentration of a basal level in a normal rat was at a hardly detectable level (a few pg/ml) even using the highly sensitive chemiluminescent enzyme immunoassay. In this paper, we prepared an anti-CCK F(ab')2 fragment which was made by pepsin digestion from the anti-CCK antiserum. The anti-CCK F (ab')2 fragment was immobilized to the Sepharose 4B gel activated BrCN and packed to column. We have extracted and concentrated CCK in the rat plasma using this column and the CCK assayed by the chemiluminescent enzyme immunoassay (CL-EIA) of CCK. The immuno-affinity column extraction system was more accurate and precise than a reversed phase gel extraction system. The mean recovery of CCK from the rat pooled plasma using the immuno-affinity column was 62.2% (n = 12) by the proposed CL-EIA. The mean +/- S. E. (n = 3) of the CCK concentration in the fasted rat plasma is 3.54 +/- 0.10 pg/ml. The plasma CCK concentrations of normal rats and those of camostat administrated rats, could be measured by the proposed CL-EIA using the immuno-affinity column as a pretreatment.

Animals↗

PubMed1997

[Novel types of receptor antagonists from the medicinal plant Garcinia mangostana].

A crude methanolic extract of the fruit hull of Garcinia mangostana L. inhibited the contraction of the isolated rabbit aorta induced by histamine and serotonin. The extract has been fractionated by silica gel chromatography, monitoring the pharmacological activity to give active compounds. On the basis of physicochemical data, the active substances were identified as alpha-mangostin and gamma-mangostin. To define the pharmacological properties of alpha-mangostin, the effect of alpha-mangostin on both histamine H1 and H2 receptors were examined by monitoring the mechanical responses of smooth muscles and measuring the radioligand binding to cultured vascular smooth muscle cells. The results suggest that alpha-mangostin acts as a selective and competitive histamine H1 receptor antagonist. The pharmacological actions of gamma-mangostin on 5-HT receptors were also investigated by using contractile response of vascular smooth muscle, platelet aggregation and radioligand binding studies. The results provide the evidence that gamma-mangostin is a selective and competitive 5-HT2A receptor antagonist. It is of great interest that the structures of alpha-mangostin and gamma-mangostin free from nitrogen atom are not resemble to the common structures of histamine and serotonin receptor antagonists. alpha-Mangostin and gamma-mangostin may become novel types of lead compounds for histamine and serotonin receptor antagonists.

Animals↗

PubMed1997

[Novel pharmacological activity of a vitamin (novel pharmacological action of vitamin D)].

The endocrine system to maintain calcium homeostasis involves the active vitamin D, as well as parathyloid hormone (PTH). Based on this 'classical' calcium-regulatory function, 1,25-(OH)2D3 and 1 alpha OHD3 was developed as the drug for vitamin D resistant rickets, renal dystrophy, and osteoporosis. Psoriasis is a chronic skin disease which is characterized by hyperproliferation and abnormal differentiation of epidermis. As an anti-psoriatic drug, 1,24R-(OH)2D3 has been on clinical use. The efficacy for psoriasis is explainable by the differentiation-inducing activity of this compound. 1,25-(OH)2D3 was also reported to suppress proliferation and induce differentiation of tumor cells including breast cancer, colon cancer and so forth, suggesting the possible therapy of malignant tumors. In immune system, active vitamin D3 exerts various effects; 1,25-(OH)2D3 suppresses proliferation and cytokine production in T cells and antibody production in B cells. Animal models of autoimmune diseases and skin-graft suggest active vitamin D becomes a novel immuno suppressant. Since 1,25-(OH)2D3 induces the synthesis of nerve growth factor (NGF), it will be a new therapy for the treatment of neuronal degenerative diseases.

Animals↗

PubMed1997

Secretion of human interleukin-2 in biologically active form by Bacillus brevis directly into culture medium.

We constructed an efficient system for synthesis and secretion of human interleukin-2 (IL-2) by Bacillus brevis. The secretion vector we constructed had strong promoters and contained the region coding for the signal peptide of the gene for B. brevis 47 cell-wall protein, followed directly by the gene encoding mature IL-2. Modification of the signal peptide and use of a protease-deficient mutant of B. brevis HPD31 increased productivity. When the signal peptide was more basic near its amino terminal and more hydrophobic in the middle region, IL-2 production increased 20 fold. Production by the mutant harboring the secretion vector was four fold that of the parent harboring the same plasmid. The yield of IL-2 increased further to 0.12 g/liter, when cultural conditions were made optimal, such by the addition of Tween 40 to the medium. The IL-2 produced by B. brevis had the same biological activity as authentic IL-2. Biologically active human IL-2 was produced efficiently and secreted directly into the medium by B. brevis.

Amino Acid Sequence↗

PubMed1997

Antioxidant activity of ferulic acid beta-glucuronide in the LDL oxidation system.

Antioxidant activity of ferulic acid beta-glucuronide, which is prepared from the plasma of feruloyl arabinose fed rats, in the CuSO4- induced LDL autoxidation system was studied. It has been found that absorbed ferulic acid occurred as the beta-glucuronide and that the antioxidant activity of ferulic acid beta-glucuronide, which has not only the hydrophobic ferulic acid moiety but also a hydrophilic sugar moiety, is stronger than ferulic acid in the LDL oxidation system.

Animals↗

PubMed1997

Diagnostic validity of bone metabolic markers for bone metastasis.

We measured bone resorption markers in tumor patients with and without bone metastases and evaluated the diagnostic validity of these biochemical parameters in the diagnosis of neoplastic bone involvement. On the basis of radiography and bone scintigraphy findings, subjects were divided into 3 groups, 83 patients without bone metastases (META(-)), 22 patients with 1 or 2 bone metastases (META(+)) and 22 patients with more than 3 bone metastases (META(++)). Among the biochemical markers, urinary pyridinoline (PYR), circulating C-terminal telopeptide of type I collagen (ICTP) and urinary N-terminal telopeptide of type I collagen (NTx) were especially sensitive and specific and increased significantly not only in META(++) but also even in META(+). The efficacy of several bone metabolic markers in differentiating between patients with and without bone metastases was evaluated by receiver-operating characteristic (ROC) analysis, and PYR, ICTP and NTx were proved to have high diagnostic validity (area under the ROC curve; 0.75 for PYR, 0.77 for ICTP and 0.77 for NTx). Furthermore, their odds ratios showed significantly high values for both META(+) and META(++)(to META(++); 7.91 for PYR, 5.33 for ICTP and 5.70 for NTx). On the other hand, urinary deoxypyridinoline (DPYR) and serum total alkaline phosphatase (ALP) showed relatively low sensitivities, the odds ratio of ALP in particular being insignificant. In conclusion, several bone metabolic markers were proved to be useful in the diagnosis of bone metastases in patients with malignancies, particularly PYR, ICTP and NTx had rather high diagnostic validities among all markers examined in this study.

Adult↗

PubMed1997

Effects of intraluminal or extraluminal endothelin on perfused rabbit basilar arteries.

The authors investigated selective intra- and extraluminal effects of endothelin (ET) on perfused basilar and extracranial arteries and also studied the interaction between ET and extraluminal oxyhemoglobin (oxyHb). The basilar, mesenteric, and femoral arteries were isolated from 23 Japanese White rabbits. After isolation of the intra- and extraluminal sides of the preparation, 3 x 10(-10) to 3 x 10(-8) mol/L of ET was administered intra- or extraluminally. After extraluminal pretreatment with 10(-5) mol/L oxyHb, 10(-5) mol/L N(G)-monomethyl-L-arginine (L-NMMA), or 10(-6) mol/L indomethacin, 10(-10) to 10(-8) mol/L of ET was administered intra- or extraluminally. Arterial contraction was evaluated by measuring the increase in the perfusion pressure gradient with a differential pressure gauge. Both intra- and extraluminal ET (10(-9) to 3 x 10(-8) mol/L) showed potent and dose-dependent vasoconstricting effects on basilar arteries (p < 0.01). The effect of ET on the basilar arteries was significantly greater than on the femoral or mesenteric arteries (both p < 0.01). The effect of intraluminal ET was enhanced by extraluminal oxyHb (p < 0.05) and L-NMMA (p < 0.01), but not by extraluminal indomethacin. Extraluminal oxyHb did not potentiate the contraction induced by extraluminal ET. These results indicate that the sensitivity of the basilar artery to intraluminal ET is greater than that of the femoral or mesenteric artery. Endothelin may act as a potent vasoconstrictor intra- as well as extraluminally under conditions such as subarachnoid hemorrhage in which oxyHb is present in the extraluminal space and endothelium-derived relaxing factors are inhibited.

Animals↗

PubMed1997

Change of tryptophan-niacin metabolism in D-galactosamine-induced liver injury in rat.

The change of tryptophan-niacin metabolism in D-galactosamine (D-galN) injected rats was investigated. Rats fed with niacin-free diets containing 40% casein for 11 days were injected with D-galN (0.8 g/kg body weight). The urinary excretions of nicotinamide and its metabolites, and the activity of liver alpha-amino-beta-carboxymuconate-epsilon-semialdehyde decarboxylase (ACMSD) (EC 4.1.1.45), a key enzyme of tryptophan-niacin metabolism, were assayed. As the result, the urinary excretions of N1-methylnicotinamide (MNA), N1-methyl-2-pyridone-5-carboxamide (2-Py), N1-methyl-4-pyridone-3-carboxamide (4-Py) and their sum (nicotinamide+MNA+2-Py+4-Py) were higher in the D-galN-injected group than in the control group. Hepatic ACMSD activity in the D-galN-injected group was lower than that of the control group. These results suggest that the increase in urinary excretion of nicotinamide and its metabolites after the injection of D-galN is considered to be attributable to a decrease in liver ACMSD activity.

Alanine Transaminase↗

PubMed1997

[Surgical management of extracranial internal carotid artery aneurysms].

Aneurysms of the extracranial internal carotid artery are rare but may present as a mass, with ischemic symptoms, or with fatal hemorrhage. We operated on aneurysms in four patients, two males and two females, whose ages ranged from 47 to 57 years. While a lot of etiological factors for the aneurysms have been known to include trauma, vascular dysplasia, infection or surgery using patch graft for carotid endarterectomy, three aneurysms in our series were atherosclerotic and one was spontaneously dissecting. One patient had focal neurological deficit due to embolism, two presented with a growing cervical mass, and one was symptom-free. The aneurysm was located proximal below the angle of the mandible in three patients and was distal above the angle in one. All patients were found able to tolerate test occlusion of the internal carotid before surgery. The aneurysm was trapped in one case (case 1) and was encased by vascular prosthesis in another (case 4). In the other two cases, arterial reconstruction after aneurysmal resection was carried out. In one case out of the two, the aneurysm was located at the level of 2nd cervical vertebral body (case 2). Vertical mandibular osteotomy was performed posteriorly to the exit of the inferior alveolar nerve from the bone, which gave a good view of the upper third of the internal carotid artery and facilitated primary end-to-end anastomosis. In the other case in which there was a dilated distal carotid artery and multiple aneurysms at the basilar and bilateral vertebral arteries (case 3), an extracranial-intracranial (EC-IC) saphenous vein bypass was inserted so as not to increase the hemodynamic stress in the posterior circulation. Except for a transient lower cranial nerve palsy in one case (case 2), there were no incidences of morbidity or death. Magnetic resonance angiography (MRA), Doppler ultrasonography or three-dimensional CT angiography (3-D-CT-A) was found useful in evaluating the change of aneurysmal size. It is essential in surgery for an internal carotid artery aneurysm to choose an appropriate approach characterized by its size and location. It may be important in cases with associated vascular lesions to estimate the potential hemodynamic change that might be induced by aneurysmal surgery.

Aneurysm↗

PubMed1997

Fractional esterification rate of cholesterol in high density lipoprotein is correlated with low density lipoprotein particle size in children.

Small low density lipoprotein (LDL) particles are thought to be more atherogenic than larger LDL particles, although this association may depend on plasma triglyceride (TG) and high density lipoprotein (HDL) levels. To help prevent coronary artery disease (CAD), it may be useful to understand risk factors during childhood and adolescence. In the present study, we evaluated low density lipoprotein particle size (LDL-size) by 2-16% gradient gel electrophoresis in 70 healthy children (30 boys and 40 girls) along with conventional lipid and lipoprotein parameters which are thought to affect LDL-size. The fractional and molar esterification rates (FER and MER) of cholesterol in plasma and HDL were also determined. As expected, plasma levels of TG, HDL-cholesterol (HDL-C) and apoA-I were closely associated with LDL-sizes in both sexes (boys: r = -0.694, 0.708 and 0.701, girls: r = -0.579, 0.551 and 0.539, P < 0.001). However, a closer association was found between FER in HDL (FER(HDL)) and LDL-size (boys: r= -0.874, girls: r= -0.642, P < 0.001). In a stepwise multiple regression analysis, FER(HDL) alone accounted for 76% and 41% of the variability in LDL-size in boys and girls, respectively. MER in HDL accounted for additional 4% and 19% in boys and girls, respectively. Other parameters, including plasma TG, HDL-C and apoA-I had no significant additional effects. Thus, the determination of FER(HDL) is useful to predict the particle size of LDL in children.

Adolescent↗