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Biomedical subjects

A Hara

Publications and source records attributed to A Hara.

At least 91 records · Page 5Linked to original sources
PubMed2000

Overproduction of spinach betaine aldehyde dehydrogenase in Escherichia coli. Structural and functional properties of wild-type, mutants and E. coli enzymes.

Betaine aldehyde dehydrogenase (BADH) catalyzes the last step in the synthesis of the osmoprotectant glycine betaine from choline. Although betaine aldehyde has been thought to be a specific substrate for BADH, recent studies have shown that human and sugar beet BADHs also catalyze the oxidation of omega-aminoaldehydes. To characterize the kinetic and stability properties of spinach BADH, five kinds of expression vectors encoding full length, mature, E103Q, E103K, and chimera BADHs were constructed. These enzymes together with Escherichia coli BADH were expressed in E. coli and purified. The affinities for betaine aldehyde were similar in the spinach and E. coli BADHs, whereas those for omega-aminoaldehydes were higher in spinach BADH than in E. coli BADH. A chimera BADH in which part of the Rossmann type fold in the spinach BADH was replaced with that of E. coli BADH, showed properties which resembled spinach BADH more than E. coli BADH. The spinach E103K mutant was almost inactive, whereas the E103Q mutant showed a similar activity for the oxidation of betaine aldehyde to that of wild type BADH, but a lower affinity for omega-aminoaldehydes. All spinach BADHs were dimers whereas E. coli BADH was a tetramer. E. coli BADH was more stable at high temperature than spinach BADHs. The E103Q mutant was most labile to high temperature. These properties are discussed in relation to the structure of spinach BADH.

Aldehyde Oxidoreductases↗
PubMed2000

Effects of Fas-mediated liver cell apoptosis on diethylnitrosamine-induced hepatocarcinogenesis in mice.

The present study was designed to investigate the effect of Fas-mediated liver cell apoptosis, induced by a hamster monoclonal antibody against mouse Fas antigen, on diethylnitrosamine (DEN)-induced hepatocarcinogenesis in mice. DEN (10 microg g(-1), intraperitoneally (i.p.)) was given to 15-day-old male C3H/HeJ mice. Three weeks after DEN treatment, Fas-mediated liver cell apoptosis induced by anti-Fas antibody resulted in a biphasic effect on induction of liver cell tumours, depending on dosage and time of antibody administration. Single or multiple treatment with high dose anti-Fas antibody (5 microg animal(-1)), induced gross liver cell damage and decreased the incidence of liver cell tumours in DEN-treated mice. In contrast, five treatments with low dose anti-Fas antibody (2 microg animal(-1)), induced dispersed localized liver cell damage and promoted the number of large-sized liver cell adenomas and hepatocellular carcinomas. These findings suggest that high dose anti-Fas antibody has a marked effect on the clearance of DEN-initiated liver cells, whereas repeated administration of low dose anti-Fas antibody promotes hepatocarcinogenesis. It is concluded that Fas-mediated liver cell apoptosis has a biphasic effect on hepatocarcinogenesis.

Adenoma↗
PubMed2000

Evaluation of the vestibular aqueduct in vestibulocochlear disorders by magnetic resonance imaging.

The visibility of the vestibular aqueduct (VA) was examined using magnetic resonance imaging (MRI) in 95 patients: 15 patients with Meniere's disease, 4 with vestibular Meniere's disease, 4 with cochlear Meniere's disease and 72 patients with other vestibular and/or cochlear disorders. In order to visualize the VA, the T2-weighted image (T2WI) and the proton-density weighted image (PDWI) were obtained in the sagittal plane with a head coil. The visibility of the VA was classified into 4 grades, i.e. grade 0 (not visible), grade 1 (partially visible with PDWI), grade 2 (partially visible with T2WI) and grade 3 (clearly visible with T2WI). The visibility of the VA was significantly lower bilaterally in Meniere's disease, vestibular Meniere's disease, cochlear Meniere's disease and idiopathic bilateral sensorineural hearing loss (IBSNHL) than in the other diseases. The differences among Meniere's disease, vestibular Meniere's disease and cochlear Meniere's disease were not significant. The significance of decreased visibility in IBSNHL is unknown so far. The VA studies using MRI strongly suggest that the pathogenesis of Meniere's disease, vestibular Meniere's disease, cochlear Meniere's disease and IBSNHL is, at least in part, related to the findings of the VA.

Adolescent↗
PubMed2000

Differential expression of beta-catenin in human glioblastoma multiforme and normal brain tissue.

Angiogenesis is considered to play an important role in the development of malignant brain tumors, especially glioblastoma multiforme (GBM). Abnormal vascular construction with a glomeruloid appearance is characteristic of GBM. beta-catenin is known as one of the adhesive molecules associated not only with cell adhesion and cell polarity, but also with carcinogenesis. We postulated the relevance of beta-catenin to vigorous endothelial proliferation in human GBM because the vascular cells (VCs) are apt to lose their cell polarity. The object of this study is to compare the immunohistochemical localization of beta-catenin in VCs between GBMs and normal brain tissues. Immunohistochemical analysis of beta-catenin for VCs in 32 GBMs and 10 normal brain tissues was performed. beta-catenin was found concentrated in the areas of vascular cell-cell junction and internal surface of the vascular lumen in all normal brains. In contrast, beta-catenin, in proliferating VCs in GBMs, was stained homogeneously and intensely in the cytoplasms of 26 cases (81.3%), in which nuclear staining of beta-catenin was also recognized in four cases (12.5%). In conclusion, the intracellular localization of beta-catenin in VCs of GBMs was found to be different from that of normal brain tissues. The changes of expression of beta-catenin may be associated with the angiogenesis or transformation of the VCs in human GBM.

Brain↗
PubMed2000

Structure-specific effects of thyroxine analogs on human liver 3 alpha-hydroxysteroid dehydrogenase.

The NADP(H)-linked oxidoreductase activity of a major isozyme of human liver 3 alpha-hydroxysteroid dehydrogenase was activated 5-, 4-, and 2-fold by D-thyroxine (T(4)), L-T(4) and DL-3,3', 5'-triiodothyronine (reverse T(3)), respectively. Kinetic analysis of the activation indicated that D-T(4), L-T(4), and reverse T(3) are non-essential activators, showing binding constants of 1.5, 1.1, and 3.6 microM, respectively. Comparison of the effects of the T(4) analogs on the activities of the mutant enzymes suggests that the binding site is composed of at least Lys-270, Arg-276, and the C-terminal loop of the enzyme. L-T(3), DL-thyronine, and D-tyrosine had no effect on the enzyme, but 3,5,3',5'-tetra- and 3,5, 3'-tri-iodo thyropropionic acids were potent competitive inhibitors with K(i) values of 42 and 60 nM, respectively, with respect to the substrate. The inhibition constant was lowered upon the activation of the enzyme by D-T(4), and the inhibition by the deamino derivatives of T(4) and T(3) disappeared upon modification of the C-terminal loop of the enzyme, but not upon replacement of Lys-270 or Arg-276 with Met. These results indicate that, depending on their structures, the T(4) analogs bind differently to two distinct sites at the active center of the enzyme to produce stimulatory and inhibitory effects.

3-Hydroxysteroid Dehydrogenases↗
PubMed2000

Coexisting renal vein thrombosis and bilateral adrenal hemorrhage: renoscintigraphic demonstration.

A rare case of simultaneous renal vein thrombosis and bilateral adrenal hemorrhage is presented, showing the utility of Tc-99m DTPA and DMSA renal scans to identify the condition and to assess renal function. The characteristic appearances of suprarenal tracer-free areas encircled by peripheral radioactive rims over the inferiorly displaced kidneys on a Tc-99m DTPA renal scan, and that of the flattened upper poles of the kidneys on a Tc-99m DMSA scan, were pathognomonic and strongly indicative of bilateral adrenal hemorrhage. These two scans also showed markedly diminished tracer uptake in the poorly functioning right thrombosed kidney. Follow-up imaging using these two renal scans well demonstrated the functional and morphologic alterations and recovery of the kidneys.

Adrenal Gland Diseases↗
PubMed2000

Tc-99m MIBG imaging in a huge clinically silent pheochromocytoma with cystic degeneration and massive hemorrhage.

I-131 metaiodobenzylguanidine scintigraphy showed marked accumulation in the walls of a clinically silent, huge cystic adrenal mass with a prominent hemorrhage in a 48-year-old man. Although a careful reexamination of the histologic specimen finally lead to a diagnosis of pheochromocytoma, the appearances of this mass on computed tomography and magnetic resonance imaging were not specific for this neoplasm, and even pathologic analysis initially indicated, incorrectly, that this lesion was a hemorrhagic hemangioma. This case shows that I-131 metaiodobenzylguanidine scintigraphy is useful for correctly diagnosing an adrenal mass with prominent cystic or hemorrhagic degeneration.

3-Iodobenzylguanidine↗
PubMed2000

Suppression of N-nitrosomethylbenzylamine-induced rat esophageal tumorigenesis by dietary feeding of 1'-acetoxychavicol acetate.

The modifying effects of 1'-acetoxychavicol acetate (ACA) on N-nitrosomethylbenzylamine (NMBA)-induced esophageal tumorigenesis were investigated in male F344 rats. At 5 weeks of age, all test animals, except those given the test chemical alone, and the control rats received s.c. injections of NMBA (0.5 mg/kg body weight/injection, three times per week) for 5 weeks. At the termination of the study (20 weeks), 75% of rats treated with NMBA alone had esophageal neoplasms (papillomas). However, the groups given a dose of 500 ppm ACA during the initiation phase developed a significantly reduced incidence of tumors (29%; P<0.01). Exposure to ACA (500 ppm) during the post-initiation phase also decreased the frequency of the tumors (38%; P<0.05). A reduction of the incidence of preneoplastic lesions (hyperplasia or dysplasia) was obtained when ACA was administered in the initiation phase (P<0.01). Cell proliferation in the esophageal epithelium, determined by assay of proliferating cell nuclear antigen (PCNA), was lowered by ACA (P<0.05). Blood polyamine contents in rats given NMBA and the test compound were also smaller than those of rats given the carcinogen (P<0.05). These findings suggest that dietary ACA is effective in inhibiting the development of esophageal tumors by NMBA when given during the initiation or post-initiation phase, and such inhibition is related to suppression of cell proliferation in the esophageal epithelium.

Animals↗
PubMed2000

An n-alkane-responsive promoter element found in the gene encoding the peroxisomal protein of Candida tropicalis does not contain a C(6) zinc cluster DNA-binding motif.

When an asporogenic diploid yeast, Candida tropicalis, is cultivated on n-alkane, the expression of the genes encoding enzymes of the peroxisomal beta-oxidation pathway is highly induced. An upstream activation sequence (UAS) which can induce transcription in response to n-alkane (UAS(ALK)) was identified on the promoter region of the peroxisomal 3-ketoacyl coenzyme A (CoA) thiolase gene of C. tropicalis (CT-T3A). The 29-bp region (from -289 to -261) present upstream of the TATA sequence was sufficient to induce n-alkane-dependent expression of a reporter gene. Besides n-alkane, UAS(ALK)-dependent gene expression also occurred in the cells grown on oleic acid. Several kinds of mutant UAS(ALK) were constructed and tested for their UAS activity. It was clarified that the important nucleotides for UAS(ALK) activity were located within 10-bp region from -273 to -264 (5'-TCCTGCACAC-3'). This region did not contain a CGG triplet and therefore differed from the sequence of the oleate-response element (ORE), which is a UAS found on the promoter region of 3-ketoacyl-CoA thiolase gene of Saccharomyces cerevisiae. Similar sequences to UAS(ALK) were also found on several peroxisomal enzyme-encoding genes of C. tropicalis.

Acetyl-CoA C-Acyltransferase↗
PubMed2000

Effect of 7-nitroindazole upon cochlear dysfunction induced by transient local anoxia.

The purpose of the present study was to further elucidate how nitric oxide (NO) is involved in cochlear anoxia-reperfusion injury. Transient local anoxia of the cochlea was induced in albino guinea pigs for 15, 30, or 60 minutes by transiently compressing the labyrinthine artery through a skull base approach. 7-Nitroindazole (7NI), a relatively selective neuronal nitric oxide synthase (nNOS) inhibitor. was intraperitoneally administered to the guinea pigs 30 minutes before the onset of local anoxia. The compound action potential (CAP) thresholds were measured before the administration of 7NI and 4 hours after the onset of reperfusion. A statistically significant reduction in the postanoxic CAP threshold shift from the preadministration value was observed in the 7NI-administered animals as compared with the control animals after 15- and 30-minute periods of anoxia. These results confirm the involvement of NO and nNOS in the cochlear injury induced by transient local anoxia.

Action Potentials↗
PubMed2000

Ranolazine attenuates palmitoyl-L-carnitine-induced mechanical and metabolic derangement in the isolated, perfused rat heart.

The effect of ranolazine, a novel anti-ischaemic drug that stimulates the activity of pyruvate dehydrogenase, on palmitoyl-L-carnitine-induced mechanical dysfunction and metabolic derangement in isolated perfused rat hearts has been studied and compared with the effect of dichloroacetate, an activator of pyruvate dehydrogenase. Rat hearts paced electrically were perfused aerobically at constant flow by the Langendorff technique. Palmitoyl-L-carnitine (4 microM) increased left ventricular end-diastolic pressure and reduced left ventricular developed pressure (i.e. induced mechanical dysfunction); it also reduced tissue levels of adenosine triphosphate and increased tissue levels of adenosine monophosphate (i.e. induced metabolic derangement). These functional and metabolic alterations induced by palmitoyl-L-carnitine were attenuated by ranolazine (5, 10, and 20 microM) in a concentration-dependent manner. In contrast, dichloroacetate (1 and 10 mM) did not attenuate palmitoyl-L-carnitine-induced mechanical and metabolic derangement. In the normal (palmitoyl-L-carnitine-untreated) heart, however, ranolazine did not modify mechanical function and energy metabolism. These results suggest that ranolazine attenuates palmitoyl-L-carnitine-induced mechanical and metabolic derangement in the rat heart, and that the beneficial action of ranolazine is not because of the energy-sparing effect or activation of pyruvate dehydrogenase.

Acetanilides↗
PubMed2000

Catalytic properties for naphthoquinones and partial primary structure of rabbit heart acetohexamide reductase.

The catalytic properties of rabbit heart acetohexamide reductase (RHAR) for naphthoquinones were examined. RHAR efficiently reduced 1,4-naphthoquinone and juglone (5-hydroxy-1,4-naphthoquinone), whereas it had little or no ability to reduce menadione (2-methyl-1,4-naphthoquinone) or plumbagin (5-hydroxy-2-methyl-1,4-naphthoquinone). The structural requirements for these four naphthoquinones and one acetohexamide analog, and the kinetic mechanism for the inhibition of acetohexamide reduction by juglone led us to conclude that the 2-methyl group of menadione and plumbagin prevents access of the substrates to the catalytic site of RHAR. Five of six peptides derived from RHAR showed 30-42% residue identities with regions in the amino acid sequence of mouse lung carbonyl reductase (MLCR) belonging to the short-chain dehydrogenase/reductase (SDR) family. The catalytically important residues (Arg-39, Ser-136, Tyr-149 and Lys-153) of MLCR were found in the peptide sequences of RHAR, despite the low residue identities between the two enzymes. RHAR is probably best classified as a member of the SDR family similar to MLCR.

Acetohexamide↗
PubMed2000

Parkinsonian symptoms as an initial manifestation in a Japanese patient with acquired immunodeficiency syndrome and Toxoplasma infection.

We studied a Japanese patient who developed parkinsonian symptoms over 3 months before the diagnosis of acquired immunodeficiency syndrome. Brain MRI showed multiple lesions with mass effect and ring enhancement in the basal ganglia and subcortical white matter suggesting Toxoplasma infection. Anti-Toxoplasma therapy and highly active antiretroviral therapy for 6 months allowed improvement of parkinsonism, brain MRI findings, and immune system.

AIDS-Related Opportunistic Infections↗
PubMed2000

Suppression of N-nitrosomethylbenzylamine-induced rat esophageal tumorigenesis by dietary feeding of auraptene.

The modifying effects of auraptene on N-nitrosomethylbenzylamine (NMBA)-induced esophageal tumorigenesis were investigated in male F344 rats. At 5 weeks of age, all animals, except those with the test chemical alone and control rats, received s.c. injections of NMBA (0.5 mg/kg body weight/injection, three times per week) for 5 weeks. At the end of the study (20 weeks), 75% of the rats treated with NMBA alone had esophageal neoplasms (papillomas). However, the groups who received a dose of 500 ppm auraptene during the initiation phase developed significantly reduced incidence of tumors (39%; P<0.05). Exposure to auraptene (500 ppm) during the post-initiation phase also decreased the frequency of the tumors (29%; P<0.01). The reduction of the incidence of severe dysplasia was obtained when auraptene was administered in the post-initiation phase (P<0.05). Cell proliferation in the esophageal epithelium determined by proliferating cell nuclear antigen (PCNA) was lowered by auraptene (P<0.01). Blood polyamine contents in rats who received NMBA and the test compound were also smaller than those of rats that received the carcinogen (P<0.05). These findings suggest that dietary auraptene is effective in inhibiting the development of esophageal tumors by NMBA when given during the initiation as well as post-initiation phases, and such inhibition is related to suppression of cell proliferation in the esophageal epithelium.

Animals↗
PubMed2000

Immunohistochemical analysis of beta-catenin in N-ethyl-N-nitrosourea-induced rat gliomas: implications in regulation of angiogenesis.

Angiogenesis plays an important role in the development of malignant brain tumors. We postulated the involvement of beta-catenin, which is associated with not only cell adhesion but also tumorigenesis in some neoplasms, in angiogenesis in brain tumors. We performed an immunohistochemical analysis of beta-catenin for vascular cells (VC) in 45 N-ethyl-N-nitrosourea (ENU)-induced rat gliomas and rat normal brain tissues. As a result, beta-catenin was found concentrated in the vascular cell-cell junction and internal surface of the vascular lumen in all normal brains. In contrast, proliferating VC in tumors were stained homogeneously in the cytoplasms of 35 cases (77.8%), among which nuclear staining was also recognized in 12 cases (26.7%). The proliferative potential of VC, which was evaluated by nucleolar organizer region-associated argyrophilic protein (AgNOR), was higher in all types of tumors than in normal brains, and was basically in parallel with the degree of malignancy of the tumors. Thus, it was suggested that the tumor vessels proliferate under a relationship with the proliferative potential of the tumors, and the intracellular localization of beta-catenin is changed under the influence of proliferative potentials of VC. beta-catenin in normal VC is considered to maintain the polarity of the vascular structure, and thus aberrant localization of beta-catenin may result in the loss of structural polarity of the tumor vessels.

Animals↗