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Biomedical subjects

H Hirano

Publications and source records attributed to H Hirano.

At least 55 records · Page 3Linked to original sources

A giant left ventricular thrombus in a patient with acute myocardial infarction--a case report.

The authors report a patient with acute anteroseptal myocardial infarction with a giant left ventricular thrombus at the apex. The patient also had nephrotic syndrome due to diabetic nephropathy. Coronary angiography showed 90% stenosis at segment 6 of the left anterior descending coronary artery. Percutaneous transluminal coronary angioplasty and intracoronary stenting were performed on the 30th day, and effective coronary blood flow was obtained. Heparin was injected intravenously for the first 7 days, and warfarin was administered thereafter. The left ventricular thrombus disappeared after 46 days. No evidence of arterial thromboembolism was found during the disappearance of the left ventricular thrombus as determined by echocardiography.

Angioplasty, Balloon, Coronary↗

Location of sialoglycoconjugates containing the Sia(alpha)2-3Gal and Sia(alpha)2-6Gal groups in the rat hippocampus and the effect of aging on their expression.

The histochemical distribution of sialoglycoconjugates in the CA1 region in the hippocampus formation of 9-week-old rats and 30-month-old rats was examined using electron microscopy in combination with two lectins, Maackia amurensis lectin, specific for Sia(alpha)2-3Gal, and Sambucus sieboldiana agglutinin, specific for Sia(alpha)2-6Gal. Each lectin stained the plasma membranes of pyramidal cells, indicating that the Sia(alpha)2-3Gal and Sia(alpha)2-6Gal groups were expressed on their plasma membranes. These lectins also bound to synapses in the stratum lacunosum molecular. The staining intensity of the lectins in the synapses in these layers was downregulated in the 30-month-old rats. These results indicated that both the Sia(alpha)2-3Gal and Sia(alpha)2-6Gal groups are expressed on these synapses and that the expression of these sialyl linkages decreases in the aged brain

Aging↗

Gastric-mucous membrane protection activity of coptisine derivatives.

Coptisine and 8-oxocoptisine were isolated as principles of the gastric-mucous membrane protection from Coptidis rhizoma. The two compounds showed stronger activity than cimetidine and sucralfate. We prepared several derivatives having a partial structure of coptisine from commercially available starting materials. The compounds obtained were tested for gastric-mucous membrane protective activity and a correlation between activity and structure was studied. Our results suggest that the partial charge of the catechol skeleton is related to activity.

Animals↗

Changes in the dissolution of tolbutamide by a traditional Chinese medicine, Sho-saiko-to (Xiao Chaihu Tang).

Dissolution rate is considered an important factor affecting absorption and efficacy after the oral administration of tolbutamide. Since in many cases traditional Chinese medicines, including Sho-saiko-to (TJ-9, Xiao Chaihu Tang), are taken with other drugs, it is likely that the dissolution and absorption of concomitant drugs in the gastrointestinal tract are influenced by the presence of traditional Chinese medicines. In this study, the effects of TJ-9 on the in vitro dissolution of tolbutamide were examined. We carried out the dissolution test of tolbutamide in the absence or presence of traditional Chinese medicines (Kakkon-to, TJ-1; Hachimi-jio-gan, TJ-7; Chorei-to, TJ-40; Shakuyaku-kanzo-to, TJ-68; TJ-9; Glycyrrhizae Radix, GR; glycyrrhizin, GL) by using a pH 1.2 dissolution medium. Tolbutamide was determined by HPLC assay. The moment parameters, ie., mean dissolution time (MDT), and the dissolution rate constant up to 20 min (kd) were estimated from the dissolution profiles on the basis of the first-order kinetics. Preparations containing GR, namely TJ-1, TJ-9 and TJ-68, significantly reduced the kd and increased the MDT of tolbutamide, while TJ-7 and TJ-40 had no effect on the early dissolution profile of tolbutamide. The extent of decrease in the kd in the presence of TJ-1, TJ-9 and TJ-68 was dependent on their GR contents. Similar inhibitory effects on the dissolution rate of tolbutamide were observed when GR alone was added to the test medium. In addition, GL, a major constituent of GR, induced a 50% increase in MDT and a 30% decrease in kd. The above results indicate that Chinese traditional preparations containing GR have an inhibitory effect on the in vitro dissolution of tolbutamide, which is derived from GL in the preparations.

Algorithms↗

Effects of sho-saiko-to (xiao chai hu tang), a Chinese traditional medicine, on the gastric function and absorption of tolbutamide in rats.

This study was carried out to investigate the effects of Sho-saiko-to (Xiao Chai Hu Tang), a Chinese traditional medicine, on the gastric function including the gastric emptying rate (GER) and intragastric pH in rats. Additionally, the effects of the GER and intragastric pH on tolbutamide absorption after oral administration were examined. The GER measured at 40 min after dosing was reduced to about 70% by the pretreatment of Sho-saiko-to (500 mg/kg). The plasma tolbutamide concentration in the rats treated with a 250 mg/kg dose of Sho-saiko-to was significantly lower than that in the control group. Plasma tolbutamide concentrations increased along with the GER in the group co-administered Sho-saiko-to, and there were significant correlations between the GERs and plasma levels in both time points at 20 and 40 min after administration. In the study using pylorus-ligated rats, Sho-saiko-to significantly elevated the intragastric pH, but induced no change in the concentrations of tolbutamide dissolved in the gastric content. Additionally, Sho-saiko-to did not change the area under the plasma concentration-time curve (AUC) of tolbutamide up to 60 min after administration into the stomach loop, and gastric absorption has been considered to minimally contribute to whole absorption of tolbutamide in the gastrointestinal tract. These results indicate that Sho-saiko-to has an inhibitory effect on the function of gastric emptying in rats. The reduced gastric emptying could affect gastrointestinal absorption, resulting in the lower plasma concentration of tolbutamide after oral administration. Furthermore, it is suggested that Sho-saiko-to can raise the intragastric pH but affect neither the intragastric dissolution nor the gastric absorption of tolbutamide.

Administration, Oral↗

Responses of transformed root culture of Atropa belladonna to salicylic acid stress.

The effect of salicylic acid (SA) on tropane alkaloid production and the responses to SA stress of transformed root cultures of Atropa belladonna (belladonna) were investigated. Treatment of A. belladonna transformed roots with 0.2 mM SA did not have any effect on tropane alkaloid production, but two compounds were produced in the medium. These were identified as the SA derivatives methylsalicylate and methyl-o-methoxybenzoate by high-resolution mass spectrometry and UV spectrometry. In contrast, treatment with 2 mM salicylic acid stimulated tropane alkaloid release from the transformed roots into the medium by up to 35% of the total alkaloids after 24 h, and the SA derivatives were not observed in the medium. These results revealed that transformed root of A. belladonna exhibits distinct by different responses to SA stress depending on the SA concentration.

Journal Article↗

Sequence specificity of the 8-hydroxyguanine repair activity in rat organs.

The base excision repair system for 8-hydroxyguanine (8-OH-Gua) is believed to play a role in the prevention of mutations, such as GC-to-TA transversion, which leads to cancer development. However, the exact repair mechanism is still unclear. In this study, we examine whether the repair activity level for 8-hydroxyguanine, one of the major forms of oxidative DNA damage, depends on the sequence of the substrate DNA. We prepared six different oligonucleotides containing 8-hydroxyguanine as substrates and reacted them with crude extracts from the livers and kidneys of 8-week-old Sprague-Dawley rats. As a result, up to a 10-fold difference in the repair activity levels was observed, depending on the substrates used. Based on this observation, we suggest that the repair systems may act with sequence specificity on the damaged DNA.

Animals↗

Myosin light chain phosphorylation is correlated with cold-induced changes in platelet shape.

Chilling induces shape changes in platelets from disks to spheres with abundant filopodia. Such changes were time-dependent and correlated well with the phosphorylation of 20-kDa myosin light chain (LC20). Both the shape changes and the phosphorylation were reversible. After the platelets had been chilled, myosin became incorporated into the Triton X-insoluble fraction. When the chilled platelets were immunocytochemically stained, anti-myosin antibody was localized with filamentous structures inside the filopodia. These results suggest that LC20 phosphorylation and subsequent interactions with actin filaments play a crucial role in the cold-induced changes in platelet shape and in the formation of filopodia.

Blood Platelets↗

Effects of mechanical stimulation on gene expression of articular chondrocytes in polylayer culture.

Mechanical loads are constantly being applied to articular cartilage. However, comparatively few studies have investigated the effects of mechanical stress on the gene expression of chondrocytes. Hence, the objective of the present study was to clarify the effects of mechanical stress on cultured chondrocytes. Articular chondrocytes of rabbits were isolated and placed in minimun essential medium eagle a modification containing 10% fetal bovine serum. The chondrocytes were cultured in polylayer in polypropylene tubes. After 48 hours, centrifugal stress (2.7 MJ) was applied once every 24 hours for 28 consecutive days. The mRNA expression of insulin-like growth factor-I (IGF-I) and cartilage-specific genes (type II collagen and aggrecan) in chondrocytes, cell count, wet tissue mass and protein content were subsequently measured. The results showed that the mRNA expression of the IGF-I gene for the stress groups was significantly greater than that of the control group from days 3 to 5 of incubation, as was the mRNA expression of the type II collagen gene from days 7 to 14 of incubation. However, there were no significant differences in the mRNA expression of the aggrecan gene between the control and stress groups. The cell count for the stress groups was significantly higher from days 7 to 28 of incubation, and the wet tissue mass and protein content were significantly higher from days 14 to 28 of incubation. These findings suggest that one of the mechanisms by which mechanical stress increases the number of cultured chondrocytes and the volume of extracellular matrix is to increase IGF-I expression at the early stage of incubation.

Aggrecans↗

A sensitive method for detecting Porphyromonas gingivalis by polymerase chain reaction and its possible clinical application.

BACKGROUND: It is useful for the clinical diagnosis of periodontitis to monitor the colonization of periodontopathic bacteria in periodontal pockets. In this study, we attempted to establish and possibly identify the clinical application of a sensitive method to detect Porphyromonas gingivalis (P.g.), one of the putative periodontopathic bacteria related to chronic periodontitis. METHODS: Genomic DNA extracted from cultured P.g. 381 and clinically isolated subgingival plaque samples were used as a template of polymerase chain reaction (PCR). We designed primers to amplify the genomic DNA coding 40 kDa outer membrane protein (OMP), one of the unique proteins to all strains of P.g. The efficiency and specificity of amplification were evaluated by agarose gel electrophoresis and subsequent Southern hybridization with a digoxygenin-labeled oligonucleotide probe. RESULTS: Fewer than 100 P.g. bacterial cells in the specimen were reproducibly detected by PCR-hybridization assay. This PCR-hybridization assay was at least 100 times more sensitive than the conventional indirect immunofluorescence assay (IIF). Furthermore, the imaging analysis showed that there is a linear correlation between the strength of the signal and the cell number of P.g. from which the template DNA was extracted semiquantitatively. It is noteworthy that the PCR assay could also be applied to detect P.g. from clinical plaque samples and that it was approximately 100 times more sensitive than a conventional IIF assay. CONCLUSION: The PCR assay established in this study can be a powerful tool to detect P.g. in periodontal pockets and monitor the colonization and/or recolonization of P.g. at the very early phase.

Bacterial Outer Membrane Proteins↗

ATP suppresses the K(+) current responses to FSH and adenosine in the follicular cells of Xenopus oocyte.

The application of either follicle-stimulating hormone (FSH) or adenosine (Ade) induces a K(+)-current response in the follicular cells surrounding a Xenopus oocyte under a voltage clamp. These K(+)-current responses are reported to be produced by an increase in intracellular cAMP. A previous application of ATP to the same cells markedly depressed the K(+)-current responses to FSH and Ade. Furthermore, a 2 min application of phorbol 12,13-dibutyrate (PDBu), an activator of protein kinase C (PKC), significantly depressed the K(+)-current responses to FSH and Ade, but it had no significant effect on the Cl(-)-current response to ATP. An application of either ATP or PDBu also depressed the K(+)-current response induced by intracellularly applied cAMP. In contrast to the effect of PDBu, the application of 1-octanol, an inhibitor of gap junction channel, significantly depressed both the Ade- and ATP-induced responses, indicating that the acting site of 1-octanol is different from that of PKC. The results suggest that the depressing effect of ATP on the FSH- and Ade-induced K(+)-current responses might be mediated by PKC activation and that the site of PKC action might be downstream of the cAMP production involved in the K(+) channel opening.

Action Potentials↗

N-linked oligosaccharides predominantly distribute in rat cerebellar cortex.

The distribution or localization of glycoconjugates in rat cerebellar cortex was investigated with 26 different kinds of lectins observed by light and electron microscopy. In paraffin-embedded tissues, PHA-L, PHA-E, DSA, WGA, ConA, LEA, LCA, PSA, and RCA-I, which mainly recognize N-linked oligosaccharide sugar structures, stained the cerebellar cortex, especially the molecular layer. PHA-L staining showed the highest selectivity for the molecular layer among these lectins. Pretreatment with N-glycanase altered the staining intensities of these lectins, whereas pretreatment with O-glycanase did not alter the intensity. In electron microscopy, the cell membrane and Golgi membranes of Purkinje cell, parallel fibers, and synaptic vesicles exhibited a positive reaction with PHA-L. Nuclear pores and synaptic vesicles were positive for WGA binding. These results suggest that there exist N-glycoside binding oligosaccharides predominantly in the cerebellar cortex, especially in the molecular layer, which sugar chains may be relevant to the synaptic transmission in the molecular layer.

Amidohydrolases↗

Angiogenic effect of thymidine phosphorylase on macrophages in glioblastoma multiforme.

OBJECT: Thymidine phosphorylase (TP) and vascular endothelial growth factor (VEGF) are known angiogenic factors; however, there are few reports in which the relationship between these two factors is addressed. The authors compared expression patterns of TP and VEGF and investigated their role in the angiogenesis of glioblastoma multiforme (GBM). METHODS: Surgical specimens from 41 cases of GBM were immunohistochemically stained for TP, VEGF, CD68 (a macrophage marker), and CD31 (an endothelial cell marker). Both TP labeling indices and VEGF immunoreactivity displayed significant correlations with vascular density. Although VEGF was diffusely distributed in the tumor, TP was strongly expressed around blood vessels and in vascular proliferation. Double labeling for TP and CD68 in 10 cases indicated that cells that reacted strongly positive for TP were almost always macrophages, and only small numbers of CD68-negative cells weakly expressed TP. The TP messenger (m)RNA expression was investigated using reverse transcription-polymerase chain reaction in six GBMs. All six specimens expressed TP mRNA. In addition, TP mRNA was detected in two of three groups of cultured GBM cells derived from surgical specimens. Macrophages, the production of which was induced from two volunteers' peripheral blood monocytes by applying macrophage colony-stimulating factor, also expressed TP mRNA. The glioma cell lines U251MG and U87MG, which barely express TP mRNA under normal conditions, expressed TP mRNA in response to interferon-beta stimulation or while in an anoxic condition. CONCLUSIONS: Although it is feasible that GBM cells can express TP depending on their growing conditions, the majority of TP-expressing cells present in GBMs appear to be infiltrating macrophages. Coexistence of VEGF and TP may indicate a synergistic upregulation for angiogenesis because VEGF exerts a chemotactic activity on macrophages that express TP.

Brain Neoplasms↗

Analysis of loss of heterozygosity on chromosome 10 in patients with malignant astrocytic tumors: correlation with patient age and survival.

OBJECT: The most frequent genetic abnormality in human malignant gliomas is loss of heterozygosity (LOH) on chromosome 10. Candidate genes on chromosome 10 that are associated with the prognosis of patients with anaplastic astrocytoma (AA) and glioblastoma (GBM) were evaluated. METHODS: The authors used 12 fluorescent microsatellite markers on both arms of chromosome 10 to study LOH in 108 primary astrocytic tumors. The LOH on chromosome 10 was observed in 11 (32%) of 34 AAs and 34 (56%) of 61 GBMs. No LOH was detected in 13 low-grade gliomas. Loss of heterozygosity was not detected in any AA in the seven patients younger than 35 years, but it was discovered in 41% of the patients older than 35 years. The prognostic significance of LOH at each locus was evaluated in 89 patients older than 15 years; 33 (37%) had supratentorial AAs and 56 (63%) had supratentorial GBMs. The Cox proportional hazards model, adjusted for patient age at surgery, the preoperative Karnofsky Performance Scale score, and the extent of surgical resection revealed that LOH on marker D10S209 near the FGFR2 and DMBT1 genes was significantly associated with shorter survival in patients with AA. The LOH on markers D10S215 and D10S541, which contain the PTEN/MMAC1 gene between them, was significantly associated with shorter survival in patients with GBM. CONCLUSIONS: In the present study it is found that LOH on chromosome 10 is an age-dependent event for patients with AAs and that LOH on marker D10S209 near the FGFR2 and DMBT1 loci is a significantly unfavorable prognostic factor. It is also reported that LOH on the PTEN/MMAC1 gene is a significantly unfavorable prognostic factor in patients with GBM.

Adult↗

Changes in molecular weight of hyaluronan and hyaluronidase activity in uterine cervical mucus in cervical ripening.

BACKGROUND: This study was undertaken to investigate changes in the forms of hyaluronan and hyaluronidase activity in cervical mucus during cervical ripening. METHODS: Uterine cervical mucus was obtained from 57 pregnant women (25 at preterm gestation, ten at term gestation, 11 within 1 week before labor, and 11 during the first stage of labor). We determined 1) concentration of hyaluronan, 2) hyaluronidase activity, and 3) molecular weight of hyaluronan in cervical mucus. Data are presented as mean and range. RESULTS: The hyaluronan concentration in mucus in the 1st stage of labor (1.58 microg/ml, 0.46-23.96) was significantly (p<0.05) higher than that in all other groups (preterm: 0.29, 0.10-0.88; term: 0.24, 0.11-0.80; within 1 week before labor: 0.30, 0.18-0.62). Hyaluronidase activity both within 1 week before labor group (3.03 min., 1.12-3.95) and in 1st stage of labor group (3.52, 0.43-5.15) was significantly (p<0.05) higher than that in preterm group (1.70, 0.00-5.47). The molecular weight of hyaluronan in cervical mucus in the 1st stage of labor (0.97x106, 0.86-1.41) was significantly (p<0.05) lower than in the preterm and term groups (preterm: 1.60, 1.21-2.20, term: 1.41, 1.21-2.20). There was a significant correlation between hyaluronidase activity and molecular weight of hyaluronan (p<0.05, r=-0.41, n=23). CONCLUSION: These findings suggest that either hyaluronidase or low-molecular weight hyaluronan could be one of the most important regulators in the process of cervical ripening.

Analysis of Variance↗

Localization of HB9 homeobox gene mRNA and protein during the early stages of chick feather development.

We performed in situ hybridization and immunohistochemical analysis of HB9 homeobox gene mRNA and protein, respectively, during chick feather development. HB9 mRNA was highly expressed in epidermal basal cells and dermal cells of the placodes and feather buds, but not in those of the interplacodes and interbud regions. HB9 protein was predominantly expressed in dermal cells of the symmetric short buds and decreased after the asymmetric bud stage when the feather bud had become elongated along the anterior-posterior (A-P) and proximal-distal (P-D) axis. These results suggest that HB9 gene is regulated in a spatiotemporal manner during feather development, and may be involved in early feather bud morphogenesis.

Animals↗

Induction of M-phase arrest and apoptosis after HIV-1 Vpr expression through uncoupling of nuclear and centrosomal cycle in HeLa cells.

The human immunodeficiency virus type 1 (HIV-1) accessory protein Vpr induces cell cycle arrest in the G2 phase of the cell cycle followed by apoptosis. The mechanism of the arrest is unknown but the arrest is believed to facilitate viral replication. In the present study, we have established cell lines that allow conditional expression of Vpr, and have examined the mechanism of cell death following Vpr expression. We found that cells expressing Vpr enter M phase after long G2 arrest but formed aberrant multipolar spindles that were incapable of completing karyokinesis or cytokinesis. This abnormality provided the basis for apoptosis, which always followed in these cells. The multipolar spindles formed in response to abnormal centrosomal duplication that occurred during the G2 arrest but did not occur in cells arrested in G2 by irradiation. Thus, the expression of Vpr appears to be responsible for abnormal centrosome duplication, which in turn contributes in part to the rapid cell death following HIV-1 infection.

Apoptosis↗