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Biomedical subjects

A Hara

Publications and source records attributed to A Hara.

At least 127 records · Page 7Linked to original sources
PubMed1999

Identification of connexins in human oral mucosa and therapeutic effect of irsogladine maleate on aphthous stomatitis.

We identified connexins 26 and 32 in human oral mucosa. The presence of the connexins indicates the presence of gap junctions in this tissue. However, immunofluorescence study found no significant differences in the expression of the connexins between patients with aphthons stomatitis and controls. Irsogladine maleate, which reinforces gap junctional intercellular communication in vitro, was effective for the treatment of transient and relapsing aphthous stomatitis, as well as symptomatic and drug-induced aphthous stomatitis. It was also useful for prevention of episodes of relapsing aphthous stomatitis, with daily administration preverting recurrence of stomatitis for more than 4 years one patient. These findings suggest that irsogladine maleate accelerates the wound healing process in oral mucosa by reinforcing gap junctional intercellular communication among oral mucosal cells; and that it is useful for the treatment and prevention of aphthous stomatitis.

Adult↗
PubMed1999

Prevention of ischemia-induced hippocampal neuronal damage by 2-deoxy-D-glucose in gerbils.

It has been reported that delayed neuronal death (DND) in the hippocampus following transient forebrain ischemia is associated with internucleosomal DNA fragmentation, indicating apoptosis. This suggests that the process of DND is energy dependent. Transient severe forebrain ischemia was induced in Mongolian gerbils by bilateral occlusion of the common carotid arteries. Post-ischemic administration of 2-deoxy-D-glucose (2-DG), a glucose antimetabolite, markedly reduced the occurrence of ischemia-induced DNA fragmentation and DND in the hippocampus. These results suggest that the reduction of energy dependent metabolism after ischemia may be an attractive therapeutic strategy for preserving hippocampal neurons vulnerable to ischemia.

Animals↗
PubMed1999

Effect of A1 adenosine receptor agonist upon cochlear dysfunction induced by transient ischemia.

The present study was undertaken to determine whether 2-chloro-N6-cyclopentyladenosine (CCPA), a highly selective A1 adenosine receptor agonist, attenuated cochlear dysfunction induced by transient ischemia or not. Ischemia of different durations (15, 30 or 60 min) was induced in 46 albino guinea pigs by transiently pressing the labyrinthine artery. CCPA or physiological saline solution was intraperitoneally administered to the animals 15 min prior to ischemia. The post-ischemic CAP threshold shift from the pre-administration value was measured 4 h after the onset of reperfusion to assess post-ischemic cochlear dysfunction. A statistically significant reduction in the CAP threshold shift was seen in CCPA-given animals after 15- and 30-min ischemia, whereas there was no statistical difference after 60-min ischemia. These results suggest that A1 adenosine receptor agonist exerts a protective effect on the cochlear injury induced by transient ischemia of intermediate duration.

Action Potentials↗
PubMed1999

The protective effect of the sympathetic nervous system against acoustic trauma.

OBJECTIVE: the cochlea is innervated by the sympathetic nerve fibers. However, the functions of those fibers in the cochlea are still controversial. The present study was designed to determine whether the sympathetic nervous system (SNS) exerts a protective or enhancing effect on acoustic trauma. METHODS: acoustic overstimulation (either of 110, 115, or 130 dB SPL for 10 min) was performed in guinea pigs during electrical stimulation of the ipsilateral cervical SNS, after its surgical elimination or in the non-treated condition. The threshold shift of the compound action potential (CAP) from the pre-exposure value was measured at 1 h and at 1 week after acoustic overstimulation. Two-way analyses of variance (ANOVAs) were completed for the SNS conditions and the frequencies. RESULTS: although no significant difference was found at 1 h after overstimulation among these three groups, the CAP threshold shift at 1 week (110 and 115 dB SPL) was significantly smaller in the SNS stimulation group than in the other two groups. CONCLUSION: a protective effect was observed in the SNS stimulation group 1 week after the exposure to acoustic overstimulation of moderate intensity (from 110 to 115 dB SPL for 10 min).

Acoustic Stimulation↗
PubMed1999

Comparison of the complexation of fluoroquinolone antimicrobials with metal ions by nuclear magnetic resonance spectroscopy.

The complexation of fluoroquinolone antimicrobials with various metal ions have been studied in aqueous solution (pD 2.5, 37 degrees C) by 1H and 13C-NMR spectroscopy. The compounds examined are levofloxacin, ciprofloxacin and lomefloxacin. In each drug, new signals have appeared by the addition of Al3+, suggesting that the complexes are formed between the drug and Al3+ and that the ligand exchange is slow on the NMR time scale. Solution structure of the major species in the presence of 2.0 mol equiv of Al3+ has been proposed based on the large downfield shifts of some specific protons. Signals of both the coordinated and free drugs have shown slight broadening at 90 degrees C due to the enhanced rate in ligand dissociation process, though the coalescence phenomena are not observed even at this temperature. Thus, the complexes are supposed to be stable at the physiological condition. Titration experiments have revealed that the binding ability of levofloxacin toward Al3+ is much stronger than that of ciprofloxacin and lomefloxacin at pD 2.5. In contrast to the complexation with Al3+, the binding of these drugs with other metal ions such as Ca2+ and Mg2+ is much weaker; NMR signals have shown no appreciable downfield shift by the addition of Ca2+ and Mg2+. Based on these results, it is concluded that the fluoroquinolone antimicrobials examined in the present study at pD 2.5 exist as stable complexes in the presence of Al3+ and the absorptivity of the drugs on oral administration could be affected by Al3+.

Anti-Infective Agents↗
PubMed1999

Neuronal apoptosis studied by a sequential TUNEL technique: a method for tract-tracing.

A novel tract-tracing procedure by using a sequential in situ terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling of DNA fragments (TUNEL) is described. This method identifies fragmented DNA transported into neuronal fibers in tissue sections of gerbil hippocampal CA1 neurons following transient forebrain ischemia. The transported DNA has been confirmed by another method, fluorescence DNA detection technique by DAPI. Many methods have been developed to study the neuroanatomical connections in the central nervous system. Principally, these techniques are based on tract-tracing studies using xenobiotics into the central nervous system. Our tract-tracing method is originated from an intrinsic marker that is produced during the apoptotic process of neurons. Furthermore, the advantage of this method is that only the selected cells undergoing apoptosis are recognized and traced to the end of the related neuronal fiber. Usually, apoptotic cells possess intact intracellular metabolic mechanisms until completion of cell death. Thus, apoptotic neurons retain the axonal transport mechanisms which enables us to detect fragmented DNA moving from nuclei to distal terminals of neuronal fibers. Since TUNEL-positive DNA movement within neuronal fibers occurs only during a limited period, it is essential that a time-course of the TUNEL technique is used to study tract-tracing of apoptotic neurons. Although this method can identify only the apical dendrites of cells that are undergoing apoptosis during the limited period, some projections of the gerbil hippocampal CA1 neurons undergoing apoptosis are clearly demonstrated.

Animals↗
PubMed1999

Construction of an autonomously replicating plasmid in n-alkane-assimilating yeast, Candida tropicalis.

A transformation system using the autonomously replicating plasmid in the n-alkane-assimilating and asporogenic diploid yeast, Candida tropicalis, was developed. For the cloning of a DNA fragment containing a potential autonomously replicating sequence (ARS) from the genomic DNA of C. tropicalis, the ura3 mutant obtained using ethylmethane sulfonate as the host and the URA3 gene amplified by PCR using the C. tropicalis genomic DNA as a selectable marker were prepared. Comparison of ARSs among yeasts revealed that the consensus sequence found in S. cerevisiae was also present in C. tropicalis. The autonomously replicating plasmid containing the putative ARS as the shuttle vector, capable of replicating in both E. coli and C. tropicalis, was first constructed. The transformation system using this plasmid, in addition to the integrative transformation system, will be applicable to genetic studies of C. tropicalis.

Journal Article↗
PubMed1999

Purification and characterization of thyroid-hormone-binding protein from masu salmon serum. A homolog of higher-vertebrate transthyretin.

We purified a thyroid-hormone-binding protein (THBP) from serum of masu salmon at the stage of smoltification when the concentrations of endogenous thyroid hormones in plasma reach the highest levels. All steps of sequential column chromatography suggest that this THBP is responsible for most L-3,5,3'-triiodothyronine-binding activity in serum at this stage. The molecular mass of this protein was estimated to be 60 kDa by gel filtration but only 15 kDa by SDS/PAGE, which suggests that it is comprised of four identical subunits. The amino acid sequence of its N-terminal portion was highly similar to those of vertebrate transthyretins. These molecular features indicate that masu salmon THBP is a homolog of transthyretins from tetrapods. However, in contrast with mammalian transthyretins, the affinity of masu salmon transthyretin for L-3,5,3'-triiodothyronine was three times greater than for L-thyroxine. This rank order affinity is similar to that of avian and frog transthyretins. Scatchard analysis revealed that masu salmon transthyretin possesses a single class of binding site for L-3,5,3'-triiodothyronine, with a Kd of 13.8 nM at 0 degrees C. Taken together with the data reported by Chang et al. [Eur. J. Biochem. (1999) 259, 534-542], these results suggest that transthyretin has changed from a L-3,5, 3'-triiodothyronine-carrier protein to a L-thyroxine-carrier protein during mammalian evolution.

Amino Acid Sequence↗
PubMed1999

Salmonid olfactory system-specific protein (N24) exhibits glutathione S-transferase class pi-like structure.

A salmonid olfactory system-specific protein (N24) that has been identified in lacustrine sockeye salmon (Oncorhynchus nerka) was characterized by biochemical and molecular biological techniques. N24 is a homodimer, and the intact molecular mass is estimated as approximately 43.3 kDa by gel filtration. Furthermore, N24 was located only in the cytosolic fraction of the olfactory tissues as determined by subcellular fractionation. cDNA encoding the lacustrine sockeye salmon N24 was isolated and sequenced. This cDNA contained a coding region encoding 216 amino acid residues and the molecular mass of this protein is calculated to be 242,224.77. The protein and nucleotide sequencing demonstrates the existence of a remarkable homology between N24 and glutathione S-transferase (GST; EC 2.5.1.18) class pi enzymes. Northern analysis showed that N24 mRNA with a length of 950 bases is expressed in lacustrine sockeye salmon olfactory epithelium. Olfactory receptor cells showed strong hybridization signals for N24 mRNA in the olfactory epithelium. N24 demonstrated glutathione binding activity in affinity-purified GST column experiments. The present study describes for the first time cDNA cloning of GST in fish olfactory epithelium.

Animals↗
PubMed1999

Effect of nitric oxide synthase inhibitor on cochlear dysfunction induced by transient local anoxia.

To evaluate whether nitric oxide (NO) plays a role in the mechanism of generation of cochlear dysfunction induced by anoxia and reperfusion, the effects of a nitric oxide synthase (NOS) inhibitor, N-nitro-L-arginine, were examined using 71 albino guinea pigs. Transient cochlear anoxia of different duration (15, 30 or 60 min) was induced by pressing the labyrinthine artery and compound action potential (CAP) was measured before and 4 h after anoxia. N-nitro-L-arginine (1-30 mg/kg) administered intraperitoneally 1 h before the onset of anoxia alleviated the cochlear dysfunction when the anoxic period was 15 or 30 min. No beneficial effect was observed, however, in the 60-min anoxia. These results indicate that NO contributes to the generation of anoxia-induced cochlear dysfunction and that NOS inhibitor has a protective effect on the cochlear injury induced by anoxia of moderate duration.

Action Potentials↗
PubMed1999

Metastatic lymph-node clearance from head and neck epidermoid carcinomas following radiotherapy.

Although tumor clearance is a common criterion in assessing the impact of radiotherapy (RT), it is not always reliable. Patterns of tumor clearance were determined using 91 metastatic lymph nodes (LNs) from 51 patients with head and neck tumors treated by definitive RT (61-80 Gy) or preoperative RT (43-65 Gy). Clearance rate (CR) was estimated as a daily volume decrement expressed as a ratio to the pre-RT LN volume. CR was greater for the so-called radioresponsive nasopharyngeal subgroups and more poorly differentiated than those of oral cavity and well-differentiated, respectively. Histologically, LNs that were removed following RT consisted mainly of fibrous tissues, necrotic tissues, and few cancer cells. There was no difference in CR between the cancer-cell-positive group (n = 21) and the cancer-cell-negative group (n = 31). Although the CR may reflect inherent radiosensitivity of tumor cells, tumor persistence predicts the amount of oncologically inactive materials rather than that of remaining cancer cells.

Carcinoma, Squamous Cell↗
PubMed1999

Dietary prevention of azoxymethane-induced colon carcinogenesis with rice-germ in F344 rats.

The modifying effect of dietary administration of defatted rice-germ and gamma-aminobutyric acid (GABA)-enriched defatted rice-germ on azoxymethane (AOM)-induced colon carcinogenesis was investigated in two experiments with male F344 rats. In the first experiment (the pilot study), the effects of the defatted rice-germ, the GABA-enriched defatted rice-germ and rice-germ on AOM-induced (15 mg/kg body wt once a week for 3 weeks) formation of aberrant crypt foci (ACF) were examined. The latter two preparations (2.5% in the diet) significantly inhibited ACF formation (P < 0.005). In the second experiment, a long-term study of the effects of rice-germ was done. One group was treated with AOM alone, four groups received the carcinogen and were fed the diets containing 2.5% rice-germ or 2.5% GABA-enriched defatted rice-germ for 5 (initiation phase) or 30 weeks (post-initiation phase), two groups were treated with rice-germ or GABA-enriched defatted rice-germ alone and one group was kept on the basal diet. At the termination of the study, dietary exposure to rice-germ during the initiation phase significantly reduced the incidence of colonic adenocarcinoma (71 versus 29%, P < 0.01). GABA-enriched defatted rice-germ or rice-germ during the post-initiation phase also decreased the frequency of colonic adenocarcinoma (71 versus 20%, GABA-enriched defatted rice-germ feeding, P < 0.01; 27%, rice-germ feeding, P < 0.01). These data suggest that constituents of rice-germ are possible dietary preventatives for human colon cancers.

Animals↗
PubMed1999

Modifying effects of a flavonoid morin on azoxymethane-induced large bowel tumorigenesis in rats.

The modifying effect of dietary exposure to a flavonoid morin during the initiation and post-initiation phases of azoxymethane (AOM)-initiated colorectal carcinogenesis was investigated in male F344 rats. A total of 55 animals were initiated with AOM by weekly s. c. injections of 15 mg/kg body wt for 3 weeks to induce colorectal neoplasms. Rats were fed a diet containing 500 p.p.m. morin for 5 ('initiation feeding') or 28 ('post-initiation feeding') weeks. Other groups contained rats treated with morin alone (500 p.p.m. in diet) and untreated rats. At the end of the study (32 weeks), the incidence of adenocarcinoma in the large intestine of rats initiated with AOM together with (43%) or followed by (29%) a diet containing morin was smaller than that of rats given AOM alone (75%). A significant difference was found between 'post-initiation feeding' and untreated groups (P = 0.023). Although both 'initiation feeding' and 'post-initiation feeding' of morin reduced polyamine levels in colorectal mucosa and blood, 'post-initiation feeding' of morin significantly decreased the proliferating cell nuclear antigen-positive index in aberrant crypt foci. 'Post-initiation feeding' of morin significantly elevated glutathione S-transferase and quinone reductase activities in the liver and large bowel, but 'initiation feeding' caused a significant elevation of these enzymes activities only in the large bowel. These results indicate that morin could exert a weak chemopreventive effect on large bowel tumorigenesis induced by AOM when fed during the post-initiation phase.

Adenocarcinoma↗
PubMed1999

Tc-99m colloid and Ga-67 imaging of splenic inflammatory pseudotumor correlation with ultrasound, CT, and MRI.

Splenic inflammatory pseudotumor is extremely rare and may mimic splenic neoplasms, such as lymphomas or hamartomas, clinically and radiologically. A case of a surgically proved splenic inflammatory pseudotumor is presented in which Tc-99m colloid SPECT and Ga-67 scintigraphy characterized the changes in the spleen, but the findings of ultrasound and unenhanced CT and MRI were nonspecific. This report indicates the utility of radionuclide imaging for diagnosing splenic inflammatory pseudotumor.

Gallium Radioisotopes↗
PubMed1999

Resolved splenic accumulation of Tc-99m HMDP after recovery of disseminated intravascular coagulation in a patient with rhabdomyosarcoma.

Unusual, intense splenic radioactivity was seen on bone scintigraphy with Tc-99m HMDP in a 14-year-old boy with alveolar rhabdomyosarcoma complicated by disseminated intravascular coagulation. Abnormal splenic radioactivity was resolved after recovery from the disseminated intravascular coagulation. During treatment of disseminated intravascular coagulation and tumors, the patient received repeated blood transfusions, resulting in iron overload, but this did not prevent the abnormal splenic uptake from resolving. This case indicates that disseminated intravascular coagulation may be a cause of splenic accumulation of bone-seeking agents, and that abnormal splenic uptake can be resolved.

Adolescent↗
PubMed1999

Chemopreventive effect of N-(2-cyclohexyloxy-4-nitrophenyl)methane sulfonamide (NS-398), a selective cyclooxygenase-2 inhibitor, in rat colon carcinogenesis induced by azoxymethane.

Non-steroidal anti-inflammatory drugs (NSAIDs) such as sulindac and indomethacin inhibit colon carcinogenesis, and selective cyclooxygenase (COX)-2 inhibitors are considered to be potential chemopreventive agents without the side effects of usual NSAIDs. We reported that NS-398, N-(2-cyclohexyloxy-4-nitrophenyl)methane sulfonamide, suppressed the formation of preneoplastic lesions, aberrant crypt foci (ACF), induced by azoxymethane (AOM) in a short-term assay of rat colon carcinogenesis. In this study, we examined the effects of long-term NS-398 administration on rat colon carcinogenesis. After three AOM treatments at weekly intervals, a dose of 10 mg/kg of NS-398 in 5% Arabic gum solution was administered by gavage three times per week in group 2 until the termination of the experiment. Rats in group 1 were fed in a basal diet and given 5% Arabic gum solution alone after AOM treatment. At 40 weeks after the first AOM treatment, all rats were killed and the whole intestines including colon were examined. While the incidences of whole intestinal and colon neoplasms in group 1 were 84.6% and 80.8%, respectively, those in group 2 (given NS-398) were 51.9% and 44.4% respectively (P=0.0177 and P=0.0103 by Fisher's exact test, respectively). The multiplicities in group 2 (0.67+/-0.78 and 0.48+/-0.58) were also decreased significantly compared with those (1.39+/-1.10 and 1.08+/-0.74) in group 1 (P<0.01 by Welch's method and P<0.002 by Student's t test, respectively). In immunohistochemistry for proliferative cell nuclear antigen (PCNA), the PCNA-stained cell index (7.40+/-0.5) in group 2 was significantly decreased from that in group 1 (14.03+/-0.82) (P<0.001 by Welch's method). The results suggest that NS-398, a selective COX inhibitor, has a chemopreventive activity against colon carcinogenesis without side-effects such as gastric ulceration.

Animals↗