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Biomedical subjects

T Ohta

Publications and source records attributed to T Ohta.

At least 235 records · Page 13Linked to original sources
PubMed2000

Role of furanocoumarin derivatives on grapefruit juice-mediated inhibition of human CYP3A activity.

With juices of grapefruit and related fruits, possible relationships between contents of six different furanocoumarins and extents of inhibition of microsomal CYP3A activity have been studied in vitro. Microsomal CYP3A-mediated testosterone 6beta-hydroxylation was inhibited by the addition of a fruit juice (2.5%, v/v) from eight different grapefruit sources, two sweeties, three pomelos, and one sour orange, whereas no clear inhibition was observed with two sweet orange juices. The inhibitory component in grapefruit juice resides mainly in the precipitate rather than in the supernatant after centrifugation. Higher amounts of (R)-6',7'-dihydroxybergamottin (DHB) were distributed in the supernatant, whereas GF-I-1, GF-I-2, GF-I-4, and the newly isolated GF-I-5 and GF-I-6 were detected predominantly in the precipitate. Mixing of five representative furanocoumarins at their detectable levels in grapefruit juice reproduced roughly the inhibitory potencies of grapefruit juice, but omission of any of the components resulted in decreased potencies. These results suggested that all the major furanocoumarins contributed to the CYP3A inhibitory properties of grapefruit juice. Furthermore, all six furanocoumarins showed stronger CYP3A inhibitory potencies after preincubation in the presence of NADPH, suggesting that both competitive and mechanism-based inhibition occur in a grapefruit juices-drug interaction.

Aryl Hydrocarbon Hydroxylases↗
PubMed2000

[Spreading patterns of hilar bile duct cancer].

Spreading patterns of hilar bile duct cancer were investigated based on cases resected in our institution and reported cases in Japan. Forty-seven patients underwent resection in our institution during the past 20 years. Three patients(12%) survived for more than 5 years. The depth of tumor invasion was m or fm in 4 and se or si in 26 patients. Positive cancer invasion in the cut end was classified as hm2 or dm2 in 8 patients and em2 in 13. Twenty-four (60%) of 40 patients investigated histologically had positive lymph node metastases. Invasion of the ss layer or deeper perineural invasion occurred in 92.5%. In terms of direct invasion of the liver, hinf1 occurred in 20(42.6%). Fourteen(29.8%) han invasion of the portal vein(more than vs1). Patients with invasion of the hepatic artery were not resected. The 5-year survival rate by cancer stage was 38% in stage I, 20% in stage II, 16% in stage III, and 0% in stage IV. Surgery was assessed as Cur A in 19 patients (46.3%), Cur B in 7 (17.1%), and Cur C in 15 (36.6%). In Cur A patients the 5-year survival rate was 18%, while that for our Cur B and Cur C patients was 0%. Our patient series was more advanced in terms of cancer stage than the statistical Japanese series and both included a significant number of noncurative cases. Hepatic resection of the right or left lobe, medial segment, and S4a and S5, combined resection of the caudal lobe, and combined portal vein resection are important as radical surgery in the treatment of this cancer.

Bile Duct Neoplasms↗
PubMed2000

Effect of labeling of plasma lipoproteins with [(3)H]cholesterol on values of esterification rate of cholesterol in apolipoprotein B-depleted plasma.

The fractional esterification rate of cholesterol in apolipoprotein B (apoB)-depleted plasma (FER(HDL)) is a good indicator of particle size distribution in high density lipoprotein (HDL) and low density lipoprotein (LDL). However, there has been a discrepancy in the absolute values of FER(HDL) published by different laboratories. Because the main difference between the methods was in the labeling of lipoproteins with [(3)H]cholesterol we investigated the effect of using Corning immunoplates and paper discs as carriers of the labeled unesterified cholesterol. We found that Corning plates trap some (3)H-labeled free cholesterol, which is released during incubation at 37 degrees C. This means that this additional (3)H-labeled free cholesterol is exposed to lecithin: cholesterol acyltransferase (LCAT) for a shorter time and artificially decreases FER(HDL). Using paper discs discarded before incubation as carriers of the (3)H-labeled free cholesterol results in complete labeling of HDL and thus yields higher values of FER(HDL).

Apolipoproteins B↗
PubMed2000

[An autopsy case of juvenile neuronal ceroid-lipofuscinosis with dilated cardiomyopathy].

We reported an autopsy case of neuronal ceroid-lipofuscinosis (NCL3) with dilatated cardiomyopathy. A 29-year-old male patient first noticed night-blindness at the age of four years. He was pointed out retinitis pigmentosa at the age of six years and developed ataxia, mental retardation, epilepsy and myoclonus, thereafter. T1 weighted MRI showed diffuse atrophy of the cerebellum, brainstem, and cerebrum, and dilatation of the ventricular system and T2-weighted MRI showed mild high signal intensity in the white matter around the trigones of the lateral ventricles. Autopsy findings showed an abundant accumulation of ceroid-lipofuscin-like lipopigments in most neurons in the central nervous system, and curvilinear bodies and lipofuscin like granules were confirmed by electron microscopy. The heart muscle showed an increase in the accumulation of ceroid-lipofuscin-like lipopigments, severe fibrosis and fatty infiltration in the myocardium. The peculiar point of this case is NCL3 with dilated cardiomyopathy.

Adult↗
PubMed2000

Epidemiological analysis of methicillin resistant Staphylococcus aureus in Thailand.

The geographical distribution of 65 clinical isolates of methicillin resistant Staphylococcus aureus (MRSA) recovered from 7 hospitals in Thailand was investigated. The presence of mecA gene in MRSA was determined by specific PCR with the use of primers 5'-GTAGTTGTCGGGTTTGGT-3' and 5'-GGTATCATCTTGTACCCA-3'. Chromosomal DNA restriction analysis with SmaI was resolved by pulsed-field gel electrophoresis (PFGE) compared with antibiotype analysis and phage type analysis. All 65 strains carried mecA gene. They all were resistant to penicillin, tetracycline, erythromycin, amoxicillin/clavulanic acid and variably resistant to gentamicin, ofloxacin, trimethoprim-sulfamethoxazole, chloramphenicol, fosfomycin and clindamycin; and all isolates were susceptible to vancomycin. A total of 19 PFGE patterns designated as type A, A1, A2, A3, A4, B, B1, C, D, E, E1, E2, F, F1, F2, G, H, I and J was identified. Type A4 and E were commonly found in every studied areas. Phage typing showed even greater variability that 52 (80%) isolates belonged to 25 different phage types; 13 (20%) isolates were non-typable. The clarity and polymorphism of the PFGE patterns enable us to discriminate between isolates which could not be differentiated by antibiogram or phage type analysis. The findings demonstrate the existence of a common epidemic MRSA clone in Thailand.

Bacterial Typing Techniques↗
PubMed2000

[An effective case of hepatic arterial infusion chemotherapy based on biochemical modulation for hepatic recurrence of non-functioning islet cell carcinoma of the pancreas].

A 55-year-old man had a metastasis in segment 3 of the liver 5 months after surgery for non-functioning islet cell carcinoma of the pancreas. The metastatic lesion increased in size in a short period, and other liver micro-metastases that could not be detected by imaging may exist, so hepatic arterial infusion chemotherapy was scheduled for 3 months. The patient underwent hepatic arterial infusion chemotherapy of 5-fluorouracil (250 mg/day/body for 5 days/week) and adriamycin (10 mg/day/body for 2 days/week) and cisplatin (10 mg/day/body for 5 days/week) and he was put on Leucovorin 30 mg/day as a biochemical modulator of 5-FU and tamoxifen 40 mg/day as a biochemical modulator of ADM. A total 6,000 mg of 5-FU, 100 mg of ADM and 240 mg of CDDP had been administered, until hepatic arterial infusion chemotherapy was discontinued because of complicated gastric ulcer. Three months later, the size of the metastatic liver tumor was reduced remarkably and no other metastasis was detected on CT scan, so he underwent partial hepatectomy of the metastatic lesion. No recurrence was found and he has survived in good physical condition during the follow-up period of 5 months after the second operation.

Administration, Oral↗
PubMed1999

Two sisters with Toriello-Carey syndrome.

Toriello-Carey syndrome comprises agenesis of the corpus callosum, telecanthus, short palpebral fissures, small nose with anteverted nares, Robin sequence, abnormally shaped ears, cardiac defect, and hypotonia. We describe two Japanese sisters with a Toriello-Carey syndrome whose phenotypes were as severe as reported male cases. The younger sister died suddenly at age 4 months. Our patients with a severe phenotype and possible parental consanguinity suggest autosomal recessive inheritance of Toriello-Carey syndrome.

Abnormalities, Multiple↗
PubMed1999

Association with cullin partners protects ROC proteins from proteasome-dependent degradation.

Cullin 1/CDC53 represents a multigene family and has been linked to the ubiquitin-mediated proteolysis of several different proteins. We recently identified two closely related RING finger proteins, ROC1 and ROC2, that share considerable sequence similarity to an APC subunit, APC11, and demonstrated ROC1 as an essential subunit of CUL1 and CDC53 ubiquitin ligases. We report here that the expression of ROC1, ROC2 and APC11 genes are induced by mitogens and remain constant during the cell cycle. Unlike other subunits of SCF and APC E3 ligases, ectopically expressed ROC family proteins are degraded by a proteasome-inhibitor sensitive pathway and are stabilized by associating with cullins. Mutations at the conserved Phe79 and His80 residues in the RING finger of ROC1 diminish its binding with cullins, resulting in a loss of cullin protection and ubiquitin ligase activity. These results suggest a potential mechanism for regulating the activity of ROC-cullin ligases through complex assembly and ROC/APC11 subunit ubiquitination.

Anaphase-Promoting Complex-Cyclosome↗
PubMed1999

Cell wall-affecting antibiotics induce expression of a novel gene, drp35, in Staphylococcus aureus.

A novel gene, drp35, of Staphylococcus aureus, which was inducible especially with cell wall-affecting antibiotics, has been cloned. Analysis of differential hybridization with mRNAs enhanced in the presence of beta-lactams resulted in two positive clones that harbored a new gene encoding a 35,845-Da protein (Drp35) and the penicillin-binding protein 2 (PBP2). Immunoblot analysis revealed that the Drp35 protein band was evidently enhanced after 30 min in the presence of beta-lactams. The Drp35 expression was also enhanced with not only beta-lactams, but also vancomycin, bacitracin, and fosfomycin. Homology search revealed that Drp35 was a new protein. Our results revealed that it was specific in S. aureus and respondent to these agents in both methicillin-resistant and -sensitive strains of S. aureus.

Amino Acid Sequence↗
PubMed1999

Role of the prostaglandin E receptor subtype EP1 in colon carcinogenesis.

Although the cyclooxygenase pathway of the arachidonic acid cascade has been suggested to play an important role in colon carcinogenesis, the molecular species of prostanoids and receptors involved have not been fully elucidated yet. We examined the development of aberrant crypt foci (ACFs), putative preneoplastic lesions of the colon, in two lines of knockout mice, each deficient in prostaglandin E receptors, EP1 and EP3, by treatment with the colon carcinogen, azoxymethane. Formation of ACFs was decreased only in the EP1-knockout mice to approximately 60% of the level in wild-type mice. Administration of 250, 500, or 1000 ppm of a novel selective EP1 antagonist, ONO-8711, in the diet to azoxymethane-treated C57BL/6J mice also resulted in a dose-dependent reduction of ACF formation. Moreover, when Min mice, having a nonsense mutation in the adenomatous polyposis coli gene, were given 500 ppm ONO-8711 in the diet, the number of intestinal polyps was significantly reduced to 57% of that in the basal diet group. These results strongly suggest that prostaglandin E2 contributes to colon carcinogenesis to some extent through its action at the EP1 receptor. Thus, EP1 antagonists may be good candidates as chemopreventive agents for colon cancer.

Animals↗
PubMed1999

Estradiol-17beta stimulates the renewal of spermatogonial stem cells in males.

In this work, we examined the functions of the female hormone "estrogen" on spermatogenesis of the Japanese eel (Anguilla japonica). Estradiol-17beta (E(2)), a natural estrogen in vertebrates, was present in the serum and its receptor was expressed in the testis during the whole process of spermatogenesis. Spermatogonial stem cell renewal was promoted by E(2) implantation but was suppressed by tamoxifen (an antagonist of estrogen). In vitro, 10 pg/ml of E(2) was sufficient to induce spermatogonial stem cell division in cultured testicular tissue, therefore confirming the in vivo observations. These results clearly show that estrogen is an indispensable "male hormone" in the early spermatogenetic cycle.

Anguilla↗
PubMed1999

Interleukin-18 induces interferon-gamma production through NF-kappaB and NFAT activation in murine T helper type 1 cells.

Interleukin-18 (IL-18) combined with anti-CD3 monoclonal antibody (mAb) induced interferon-gamma (IFN-gamma) production by T helper type 1 (Th1) cells. Neither IL-18 nor anti-CD3 mAb alone induced production of IFN-gamma. Although treatment with IL-18 alone induced full activation of NF-kappaB in Th1 cells, it was not sufficient for the production of IFN-gamma. To examine the importance of NF-kappaB activation in IFN-gamma production, we established Th1 cells which expressed a transdominant IkappaBalpha mutant. In these cells, activation of NF-kappaB and production of IFN-gamma by IL-18 were suppressed. On the other hand, we examined the T cell receptor (TCR)/CD3-mediated signaling pathway. FK506, an inhibitor of NFAT activation, inhibited IFN-gamma production by IL-18 without any effect on the NF-kappaB activation. We conclude that dual signaling consisting of IL-18-induced NF-kappaB activation and TCR/CD3-mediated NFAT activation is crucial for IFN-gamma production by IL-18 in murine Th1 cells.

Animals↗