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Biomedical subjects

H Hirano

Publications and source records attributed to H Hirano.

At least 145 records · Page 8Linked to original sources
PubMed1998

Quantitative differences in telomerase activity among malignant, premalignant, and benign ovarian lesions.

Telomerase activation has been demonstrated in both cancers and some noncancerous lesions. However, few studies have determined levels of telomerase activity in these lesions. In the present study, using a recently developed stretch PCR assay, telomerase activity was quantitatively determined in a variety of ovarian lesions including 36 ovarian cancers, 5 ovarian low potential malignancy (LPM) lesions, 10 ovarian cysts, and 12 normal ovaries. Telomerase activity was normalized to control activity (100 units) in C33A cell line and given in relative units. Telomerase activity in ovarian cancer (51 +/- 7 units, mean +/- SE) was significantly higher than that in LPM lesions, ovarian cysts, and normal ovaries (7 +/- 3, 10 +/- 2, and 10 +/- 2 units, respectively; P < 0.001). Interestingly, all LPMs, ovarian cysts, and normal ovaries exhibited low telomerase activity less than 30 units, and no significant difference in level of telomerase activity was found among them. We also found a significant correlation between the level of telomerase activity and the clinical stage of ovarian cancer. Our quantitative telomerase assay thus clearly distinguished telomerase activity in ovarian cancers from that in LPM lesions and ovarian cysts. Significant levels of telomerase activation frequently occurred in cancer but rarely occurred in premalignant and benign lesions, suggesting that telomerase activation is a critical step in cancer development.

Female↗
PubMed1998

[Brain magnetic resonance imaging findings in two cases of Hunter's syndrome].

Magnetic resonance (MR) imaging findings in two cases of Hunter's syndrome [mucopolysaccharidosis (MPS) type II A] are reported. The first case is a 15-year-old boy in whom the diagnosis of Hunter's syndrome was made at 2 years of age on the basis of increased glycosaminoglycans in the urine, developmental delay, characteristic faces, joint contraction, family histories, and radiological characteristics including oar-like deformed ribs and dysplasia of lumbar vertebrae. MR images showed marked enlargement of the lateral ventricles and third ventricle. The cerebral cortical sulci were diffusely dilated. Abnormal intensity lesions in the lateral part of the lentiform nucleus, the subcortex of the insula, the pons, and the right thalamus were seen. Diffuse hyperintensity throughout the periventricular white matter is also seen on T2-weighted images. The second case is a 3-year-old boy, born at immature delivery. At 2 months of age, he was admitted to a pediatric department because of liver dysfunction, inguinal hernias and umbilical hernia. The diagnosis of Hunter's syndrome was made by developmental delay, gargoylism, joint contraction, kyphosis, and biochemical investigation of urine. Urinary glycosaminoglycans significantly increased. Skeletal radiography showed dysplasia of the lumbar vertebrae and acetabulum. T1-weighted MR images demonstrated numerous hypointense spots in the corpus callosum and the cerebral white matter, presumably suggesting large perivascular spaces. Multiple cystic changes appeared to be hyperintense on T2-weighted images. Numerous linear hyperintense lesions were visible in the corona radiata. Patchy areas of hyperintense areas were seen, more prominent in the parietal lobes. Neuropathological examinations in cases of Hunter's syndrome have previously shown marked dilatation of ventricular system, large perivascular spaces secondary to mucopolysaccharide storage, demyelination and gliosis in the white matter and so forth. MR findings correlated well with previously reported neuropathological findings. MR study is not only useful for diagnosing Hunter's syndrome but also helpful to follow the pathological status.

Adolescent↗
PubMed1998

The relationship between amniotic fluid interleukin-6 concentration and histologic evidence of chorioamnionitis.

BACKGROUND: Chorioamnionitis is considered to be one of the important causes of preterm labor. To investigate the relationship between inflammatory cytokines in amniotic fluid and the histologic evidence of chorioamnionitis, we studied amniotic fluid interleukin-6 (IL-6) levels in patients with preterm labor. METHODS: Between 1993 and 1996, we obtained amniotic fluid by amniocentesis from 110 patients before 32 weeks of gestation who had preterm labor on admission. We measured IL-6 levels in the amniotic fluid with an ELISA method. Histologic examination of placentae and fetal membranes after delivery was evaluated. As controls, we measured IL-6 levels in the amniotic fluid of 37 patients without preterm labor. Seventy-eight patients delivered after 35 weeks of gestation, and 32 patients delivered before 34 weeks of gestation. Analysis was conducted using Mann-Whitney U test and Scheffe's multiple comparison test. RESULTS: Amniotic fluid IL-6 levels in patients delivering before 34 weeks were significantly higher than those in patients delivering after 35 weeks (p<0.01). IL-6 levels in the amniotic fluid were significantly different among control patients, patients without chorioamnionitis and those with histologic stages I, II and III which means subchorionic intervillositis, chorionitis and amnionitis, respectively (controls vs patients with stage I, II, III: p<0.001, patients without chorioamnionitis vs those with stage II, III, stage I vs II, stage II vs III: p<0.01). The IL-6 concentration in the amniotic fluid associated with histologic stages II or III was above 3500 pg/ml (sensitivity: 87.5%, specificity: 89.5%). CONCLUSIONS: Our findings indicate that amniotic fluid IL-6 may have a sensitive diagnostic and prognostic value in the management of preterm labor and is an index of the severity of chorioamnionitis during pregnancy.

Amniotic Fluid↗
PubMed1998

Excretion of ofloxacin into saliva in rats with renal failure.

To clarify effects of renal failure on salivary distribution of ofloxacin (OFLX), a quinolone antibiotics, blood, parotid and mandibular saliva were collected from the single-step 5/6th-nephrectomized and sham-operated (control) rats after bolus i. v. administration of OFLX (5 mg/kg). The concentrations of OFLX in these samples were determined by high-performance liquid chromatography. Renal failure induced by the partial nephrectomy significantly elevated plasma levels and cumulative salivary excretion of OFLX when compared to control rats. Total body clearance was significantly decreased by the renal failure, although salivary clearance of the partially nephrectomized rats was about three times larger than that of the control. At the terminal phase, the saliva/plasma concentration ratios of OFLX for parotid and mandibular saliva in control rats was 0.249 +/- 0.180 and 0.136 +/- 0.024, respectively, and there was a significant difference between both salivary glands. The saliva/plasma concentration ratios in the rats with renal failure were significantly greater than those in the control group in both parotid (about 3.2 times) and mandibular (about 2.5 times) saliva. The results of this study suggest that the salivary excretion of OFLX is significantly increased by renal failure and a glandular difference in the salivary excretion of OFLX exists in both rats with normal and impaired renal function.

Animals↗
PubMed1997

Distinct neuronal lineages of the ascidian embryo revealed by expression of a sodium channel gene.

The ascidian larva contains tubular neural tissue, one of the prominent anatomical features of the chordates. The cell-cleavage pattern and cell maps of the nervous system have been described in the ascidian larva in great detail. Cell types in the neural tube, however, have not yet been defined due to the lack of a suitable molecular marker. In the present work, we identified neuronal cells in the caudal neural tube of the Halocynthia embryo by utilizing a voltage-gated Na+ channel gene, TuNa I, as a molecular marker. Microinjection of a lineage tracer revealed that TuNa I-positive neurons in the brain and in the trunk epidermis are derived from the a-line of the eight-cell embryo, which includes cell fates to epidermal and neural tissue. On the other hand, TuNa I-positive cells in the more caudal part of the neural tissue were not stained by microinjection into the a-line. These neurons are derived from the A-line, which contains fates of notochord and muscle, but not of epidermis. Electron microscopic observation confirmed that A-line-derived neurons consist of motor neurons innervating the dorsal and ventral muscle cells. Isolated A-line blastomeres have active membrane excitability distinct from those of the a-line-derived neuronal cells after culture under cleavage arrest, suggesting that the A-line gives rise to a neuronal cell distinct from that of the a-lineage. TuNa I expression in the a-line requires signals from another cell lineage, whereas that in the A-line occurs without tight cell contact. Thus, there are at least two distinct neuronal lineages with distinct cellular behaviors in the ascidian larva: the a-line gives rise to numerous neuronal cells, including sensory cells, controlled by a mechanism similar to vertebrate neural induction, whereas A-line cells give rise to motor neurons and ependymal cells in the caudal neural tube that develop in close association with the notochord or muscle lineage, but not with the epidermal lineage.

Animals↗
PubMed1997

Isolation and expression of the gene which encodes a novel enzyme with polymethoxygalacturonate-degrading activity in Trichosporon penicillatum.

The novel gene named PSX1, encoding a new protopectinase with the polymethoxygalacturonase activity, was isolated from Trichosporon penicillatum. Nucleotide sequencing revealed that the PSX1 gene is composed of 1080 bases (360 amino acids, 38,747 Da). The N-terminal amino acid sequences of the open reading frame correspond to a signal peptide and propeptide processed by a Kex2-like proteinase. Mature PPase SX1 was composed of 334 amino acids (36,121 Da). PPase SX1 produced by a S. cerevisiae transformant harboring the PSX1 gene degraded methoxylated polygalacturonic acid as a substrate, but not degraded unmethoxylated polygalacturonic acid.

Amino Acid Sequence↗
PubMed1997

Identification and characterization of a novel human phosphatidylinositol 4-kinase.

The extensive sequence homology that exists among the catalytic domains of phosphatidylinositol 3- and 4-kinases allowed us to clone a novel human gene encoding a putative phosphatidylinositol kinase, NPIK. Among other known phosphatidylinositol 3- and 4-kinases, NPIK was most closely related to yeast PIK1 phosphatidylinositol 4-kinase. Several forms of NPIK cDNAs were isolated, and expression of NPIK message was detected in a wide variety of tissues. Fluorescence in situ hybridization and radiation hybrid analyses assigned the NPIK gene to human chromosome 1. Recombinant NPIK protein catalyzed a conversion from phosphatidylinositol to phosphatidylinositol 4-phosphate. The catalytic activity of NPIK was augmented by Triton X-100, and was reduced in the presence of adenosine. Using green fluorescent protein system we determined that NPIK is localized in the cytoplasm. Taken together, the data suggest that NPIK may play a pivotal role in regulating the synthesis of phosphatidylinositol 4-phosphate at the site(s) accessible from cytoplasm.

1-Phosphatidylinositol 4-Kinase↗
PubMed1997

Tissue-specific and growth-regulated expression of CD44 variable exon determinants in the mouse.

CD44 is a polymorphic transmembrane glycoprotein widely expressed in lymphocytes and epithelial cells. CD44 polymorphism reflects both posttranslational modification and alternative splicing of up to 10 variably expressed exons in the membrane-proximal CD44 extracellular domain. An analysis of CD44 variable exon-containing isoforms in the mouse was carried out by generating a panel of monoclonal antibodies against variable region determinants of CD44. Immunohistochemical analysis demonstrated selective patterns of expression of CD44 variable exon determinants in normal tissues, and flow cytometric analysis identified expression of CD44 variable exon-dependent determinants in epithelial and lymphoid cell lines. Regulation of alternative splicing was studied by characterization of cell surface expression of CD44 variable exon determinants on HC11 mammary epithelial cells, and it was demonstrated that variably spliced isoforms are selectively regulated as a function of growth phase in vitro. These results demonstrate the tissue-specific and growth-regulated expression of the CD44 isoform at the level of cell surface protein products and identify isoform-specific determinants that can be targeted in analysis of isoform-specific function.

Animals↗
PubMed1997

Isolation and characterization of a GDP/GTP exchange protein specific for the Rab3 subfamily small G proteins.

The Rab small G protein family, consisting of nearly 30 members, is implicated in intracellular vesicle trafficking. They cycle between the GDP-bound inactive and GTP-bound active forms, and the former is converted to the latter by the action of a GDP/GTP exchange protein (GEP). No GEP specific for each Rab family member or Rab subfamily has been isolated. Here we purified a GEP from rat brain with lipid-modified Rab3A as a substrate. The purified protein was specifically active on Rab3A, Rab3C, and Rab3D of the Rab3 subfamily. Of these subfamily members, Rab3A and Rab3C are implicated in Ca2+-dependent exocytosis, particularly in neurotransmitter release. This GEP (Rab3 GEP) was active on the lipid-modified form, but not on the lipid-unmodified form. Rab3 GEP showed a minimum molecular mass of about 200 kDa on SDS-polyacrylamide gel electrophoresis. We cloned its cDNA from a rat brain cDNA library and determined its primary structure. The isolated cDNA encoded a protein with a Mr of 177,982 and 1,602 amino acids, which showed no homology to any known protein. The recombinant protein exhibited GEP activity toward Rab3A, Rab3C, and Rab3D. Northern blot and Western blot analyses indicated that Rab3 GEP was expressed in all the rat tissues examined with the highest expression in brain.

Amino Acid Sequence↗
PubMed1997

Transport of glucose across the blood-tissue barriers.

In specialized parts of the body, free exchange of substances between blood and tissue cells is hindered by the presence of a barrier cell layer(s). Specialized milieu of the compartments provided by these "blood-tissue barriers" seems to be important for specific functions of the tissue cells guarded by the barriers. In blood-tissue barriers, such as the blood-brain barrier, blood-cerebrospinal fluid barrier, blood-nerve barrier, blood-retinal barrier, blood-aqueous barrier, blood-perilymph barrier, and placental barrier, endothelial or epithelial cells sealed by tight junctions, or a syncytial cell layer(s), serve as a structural basis of the barrier. A selective transport system localized in the cells of the barrier provides substances needed by the cells inside the barrier. GLUT1, an isoform of facilitated-diffusion glucose transporters, is abundant in cells of the barrier. GLUT1 is concentrated at the critical plasma membranes of cells of the barriers and thereby constitutes the major machinery for the transport of glucose across these barriers where transport occurs by a transcellular mechanism. In the barrier composed of double-epithelial layers, such as the epithelium of the ciliary body in the case of the blood-aqueous barrier, gap junctions appear to play an important role in addition to GLUT1 for the transfer of glucose across the barrier.

Animals↗
PubMed1997

Dopaminergic and cholinergic interaction in cataleptic responses in mice.

The cataleptogenic effects of haloperidol, a dopamine D2 receptor antagonist; SCH23390, a D1 receptor antagonist; physostigmine, a cholinesterase inhibitor; and pilocarpine, a muscarinic M1 receptor agonist, were challenged by pretreatment of mice with SKF38393, a dopamine D1 receptor agonist; apomorphine, a dopamine D1/D2 receptor agonist (mainly D2 receptor); pirenzepine, a muscarinic M1 receptor antagonist; and scopolamine, a muscarinic M1/M2 receptor antagonist. The effect of physostigmine and pilocarpine on haloperidol and SCH23390 cataleptic responses was also examined. Each of the challenging agents blocked one or more of the cataleptogenic agents, but only scopolamine blocked all four. Pirenzepine blocked cataleptic responses induced by SCH23390 and pilocarpine, but not those by haloperidol and physostigmine. The results of this study suggest that the action of physostigmine (endogenous acetylcholine) on M2 receptors might be more potent than that on muscarinic M1 receptors. A further interesting observation was that the haloperidol-induced catalepsy was enhanced by physostigmine pretreatment, but not by pilocarpine pretreatment, whereas the SCH23390-induced catalepsy showed the opposite spectrum of enhancement by the two cholinergic agonists. We conclude that, although the four cataleptogenic agents act via the dopaminergic-cholinergic systems, their pharmacological differences may be due largely to the different receptor subtypes that are involved in the mediation of catalepsy produced by each agent. Thus, dopamine receptors not only influence the cholinergic muscarinic receptors, but muscarinic M1 and M2 receptors also might mediate dopamine D1 and D2 receptor responses, respectively. The results suggest that there are, at the least, relationships between muscarinic M1 receptors and dopaminergic D1 receptors, and between muscarinic M2 receptors and dopaminergic D2 receptors. Dopamine D1 and D2 receptors may interact in a synergistic fashion on dopaminergic systems, but act independently of each other in influencing other system such as cholinergic neurons.

Animals↗
PubMed1997

Screening of rice genes from the cDNA catalog using the data obtained by protein sequencing.

The partial amino acid sequences of 121 rice proteins separated by two-dimensional gel electrophoresis (2D-PAGE), were determined for a protein sequence data file. In the Rice Genome Research Program (RGP), more than 20,000 cDNA clones randomly selected from rice cDNA libraries have been sequenced to construct a cDNA catalog. Complimentary DNAs encoding about 30% of proteins in the protein sequence data file could be identified in the catalog by computer search. It was deduced that 20,000-40,000 genes are present in the rice genome. Only half of about 20,000 cDNAs sequenced in the RGP, corresponding to 1/4-1/2 of genes present in the entire rice genome, should have unique sequences after considering gene redundancy. This is consistent with the fact that the cDNAs encoding about 30% of the sequenced proteins could be identified in the catalog. If the size of the cDNA catalog is enlarged further, cDNAs encoding all proteins separated by 2D-PAGE could be easily identified from the catalog by using the protein sequence data.

Amino Acid Sequence↗
PubMed1997

Immunohistochemical expression of glucose transporter-1 in human penile proliferative lesions.

Glucose transporters (GLUTs) are a family of membrane proteins responsible for the transport of glucose across cellular membranes. In terms of their mRNA levels, they have been reported to be expressed in some human tumours. However, the immunohistochemical localization of GLUTs in human urogenital lesions has rarely been studied. This study was performed to evaluate the expression of GLUT1 in penile proliferative lesions (18 cases of penile carcinoma and 13 cases of condyloma acuminatum). Using an isoform-specific anti-GLUT1 antibody, formalin-fixed paraffin-embedded sections were stained by the avidin-biotin complex method. In all cases of penile carcinoma, GLUT1 staining was diffusely recognized on the cell membrane of the carcinoma cells in the mainly infiltrating areas. However, the inner areas of the tumour were more weakly and focally stained. The intensity of staining for the penile carcinoma (staining score = 2.8 +/- 0.6) was stronger than that for condyloma acuminatum and that for adjacent non-proliferative areas. All cases of condyloma acuminatum showed a diffuse staining on the cell membrane in the basal and intermediate layers (staining score = 2.4 +/- 0.5). Non-proliferative (histologically normal) glans areas adjacent to the above lesions expressed the weakest GLUT1 staining only in the stratum basale (staining score = 1.8 +/- 0.5). These three areas showed significantly different staining scores from each other (p < 0.01). In conclusion, GLUT1 is expressed dominantly in penile proliferative lesions, especially in infiltrating areas of penile carcinoma.

Adult↗
PubMed1997

Mechanism of 'bystander effect' killing in the herpes simplex thymidine kinase gene therapy model of cancer treatment.

'Bystander' killing of adjacent wild-type tumor cells was seen when tumors transduced with the herpes thymidine kinase gene were treated with the antiviral agent ganciclovir (GCV). Some tumors were 'bystander-sensitive' while others were 'bystander-resistant'. Mixtures of different 'sensitive' tumor lines showed cross-transfer of bystander killing, while in mixtures of 'resistant' with 'sensitive' tumors, the resistant phenotype was predominant. Using 3H-GCV with 'sensitive' mixtures, phosphorylated 3H-GCV was found in both herpes thymidine kinase transduced and unmodified cells, while 'resistant' cell combinations showed little or no transfer of phosphorylated GCV between cells. The capacity of intracellularly produced nucleotide toxin to spread from cell to cell within a tumor mass effectively amplifies the apparent efficiency of gene transfer in the tumor and makes feasible the use of this system for therapy of localized cancer.

Adenocarcinoma↗