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Biomedical subjects

A Nishimura

Publications and source records attributed to A Nishimura.

At least 73 records · Page 4Linked to original sources
PubMed1999

Effects of the Japanese herbal medicine "Sho-saiko-to" (TJ-9) on interleukin-12 production in patients with HCV-positive liver cirrhosis.

Interleukin-12 (IL-12) is an important cytokine for maintenance of normal systemic defense and bioregulation. The Japanese herbal medicine Sho-saiko-to (TJ-9) has been administered to 1.5 million Japanese patients with chronic liver diseases. TJ-9 is known to significantly suppress cancer development in the liver and has macrobiotic effects. In the present study, we examined the in vitro production of IL-12 by circulating mononuclear cells from liver cirrhosis patients and the effects of TJ-9 on IL-12 production. The monocyte/macrophage fraction and the lymphocyte fraction of peripheral blood were obtained from 11 HCV-positive liver cirrhosis patients and 12 healthy subjects. Interleukin-12 levels in the supernatants were measured using ELISA kits. The levels of IL-12 produced by the patients' fractions were significantly lower than those produced by healthy subjects (p < 0.01, p < 0.05). However, when TJ-9 was added to the cultures, the IL-12 production levels in both cell fractions increased approximately three fold, and the levels from the monocyte/macrophage fraction were almost the same as those from healthy subjects. This effect of TJ-9 was attributable to two of its seven herb components, that is, scutellaria root and glycyrrhiza root. One possible mechanism for the macrobiotic effects of TJ-9 on liver cirrhosis patients may be the improvement in IL-12 production.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1999

Changes in Bcl-2 and Bax expression in rat tongue during 4-nitroquinoline 1-oxide-induced carcinogenesis.

Bax is considered as a main effector of apoptosis. Bax forms homodimers and also heterodimers with Bcl-2. The function of the Bax-Bax dimer in active cell death is antagonized by Bax-Bcl-2 heterodimers. Thus, the ratio of Bcl-2 and Bax should control the susceptibility of cells to those stimuli that induce apoptotic cell death. An increase in apoptotic change has been shown in many carcinomas. In the present study, the changes in Bcl-2 and Bax expression in the tissue during carcinogenic transformation were examined immunohistochemically by means of the 4-nitroquinoline 1-oxide (4NQO)-induced carcinoma model. Animals were divided into 7 groups of 10 rats each, and given 50 ppm 4NQO solution as drinking water for 4, 8, 12, 16, 20, or 24 weeks. Ten animals were used as controls. Gradual increases in the numbers of Bcl-2- and Bax-positive cells were shown corresponding to the progression of experimental carcinogenesis. Statistically significant differences in Bcl-2 and Bax expression were demonstrated between control and four-week treatment groups (p < 0.01), and between control and eight-week treatment groups (p < 0.05), respectively. Levels of both proteins remained high after the period of dysplastic change of the epithelium. In conclusion, Bcl-2 and Bax are involved in the progression of 4NQO-induced carcinoma.

4-Nitroquinoline-1-oxide↗
PubMed1999

Initiation of shoot apical meristem in rice: characterization of four SHOOTLESS genes.

The regulatory mechanism of shoot apical meristem (SAM) initiation is an important subject in developmental plant biology. We characterized nine recessive mutations derived from four independent loci (SHL1-SHL4) causing the deletion of the SAM. Radicles were produced in these mutant embryos. Concomitant with the loss of SAM, two embryo-specific organs, coleoptile and epiblast, were lost, but the scutellum was formed normally. Therefore, differentiation of radicle and scutellum is regulated independently of SAM, but that of coleoptile and epiblast may depend on SAM. Regeneration experiments using adventitious shoots from the scutellum-derived calli showed that no adventitious shoots were regenerated in any shl mutant. However, small adventitious leaves were observed in both mutant and wild-type calli, but they soon became necrotic and showed no extensive growth. Thus, leaf primordia can initiate in the absence of SAM, but their extensive growth requires the SAM. An in situ hybridization experiment using a rice homeobox gene, OSH1, as a probe revealed that shl1 and shl2 modified the expression domain of OSH1, but normal expression of OSH1 was observed in shl3 and shl4 embryos. Accordingly, SHL1 and SHL2 function upstream of OSH1, and SHL3 and SHL4 downstream or independently of OSH1. These shl mutants are useful for elucidating the genetic program driving SAM initiation and for unraveling the interrelationships among various organs in grass embryos.

Gene Deletion↗
PubMed1999

Studies on disease-modifying antirheumatic drugs. III. Bone resorption inhibitory effects of ethyl 4-(3,4-dimethoxyphenyl)-6,7-dimethoxy-2-(1,2,4-triazol-1-ylmethyl) quinoline-3-carboxylate (TAK-603) and related compounds.

In the course of our studies aimed at obtaining new drugs for treatment of bone and joint diseases, chemical modification of the potent bone resorption inhibitors justicidins, was performed and various naphthalene lactones, quinoline lactones and quinoline derivatives bearing an azole moiety at the side chain were prepared. Their inhibitory effects on bone resorption were evaluated by Raisz's method, and several compounds, including ethyl 4-(3,4-dimethoxyphenyl)-6,7-dimethoxy-2-(1,2,4-triazol-1-ylmeth yl)quinoline -3-carboxylate (6c, TAK-603), were found to have activities comparable with or superior to the justicidins. The 4-(3-isopropoxy-4-methoxy)-phenyl derivative (6d), in particular, displayed a marked increase in potency. TAK-603 and compound 6d were very effective in preventing osteoclast formation and bone resorption by mature osteoclasts. Further, TAK-603 was shown to be effective in preventing bone loss in ovariectomized mice.

Animals↗
PubMed1999

Clinicopathologic significance of protein induced vitamin K absence or antagonist II and alpha-fetoprotein in hepatocellular carcinoma.

Protein induced vitamin K absence or antagonist II (PIVKA-II) and alpha-fetoprotein (AFP) have been considered useful serum markers of hepatocellular carcinoma (HCC). In this study, we examined the clinicopathologic significance of these tumour markers in patients with HCCs by measuring their serum levels and performing immunohistochemistry. We studied 349 Japanese patients with HCCs. Their serum PIVKA-II and AFP levels were determined by enzyme immunoassay before treatment. We examined the correlations between serum PIVKA-II and AFP levels and tumour size, presence of satellite nodules, histologic HCC grade, and concomitant liver diseases and subjected tumour tissues to immunohistochemical staining to detect PIVKA-II and AFP expression. The serum PIVKA-II levels of patients with poorly differentiated HCCs were significantly higher than those of patients with well and moderately differentiated HCCs (p<0.05) and they were higher in HCC patients with than without satellite nodules. The serum AFP levels were influenced significantly by concomitant liver diseases, but not by the other factors. Immunohistochemical staining revealed the PIVKA-II expression levels of poorly differentiated HCCs were higher than those of well and moderately differentiated HCCs (p<0.05). Some HCC cells were PIVKA-II-positive, others were AFP-positive, and some expressed both. The serum PIVKA-II concentration was a better indicator of HCC than AFP, as it was not influenced by concomitant liver diseases. The presence of PIVKA-II in serum correlated with the presence of satellite nodules and the histologic HCC grade, a result concordant with the immunohistochemical findings.

Aged↗
PubMed1999

Preliminary investigation of resistance of plasmid DNA to neon ion beams using transformation into recipient Escherichia coli cells.

The sensitivity of the vector plasmid pKmK8 DNA to neon ion beams was studied under dry conditions. This plasmid contains the cloning vector pJKKmf(-) and a 3.6 kbp segment encoding the Escherichia coli crp gene that can be used in mutagenesis analysis. The survival curve of the plasmid indicated an exponential profile and a D10 value of about 16 kGy in the E. coli wild-type strain for DNA repair capability. This was similar to the D10 value for the shuttle vector plasmid pZ189 DNA. Therefore, it was assumed that the excision repair system in E. coli was not effective for repairing DNA lesions induced by irradiation with heavy ion beams.

DNA Damage↗
PubMed1999

[Evaluation of 18F-FDG positron emission tomography (PET) in the detection of unknown primary tumors].

18F-fluorodeoxyglucose positron emission tomography was able to identify previously unknown primary tumors in 2 of 4 patients after an unsuccessful conventional diagnostic workup such as chest radiography, ultrasound, computed tomography, MRI and various endoscopies. The 2 patients in which the primary tumors were detected proved to have a carcinoma of the lung, one of the patients received radiotherapy and chemotherapy after the detection of the primary tumor by FDG PET. The primary tumor of the lung demonstrated no focal FDG uptake after the successive treatment. On the other hand, in one patient with prostatic carcinoma and another in which the primary tumor has yet to be detected, FDG PET was unable to identify the primary tumor. This suggests a limitation of PET studies in detecting cancers. Because of increased glycolysis in cancer cells, FDG PET can be used to detect cancers with its high sensitivity, surveying the entire body non-invasively in one session. PET has the advantage of detecting primary tumors of an unknown origin when compared to conventional diagnostic studies.

Aged↗
PubMed1999

Upstream element of the sea urchin arylsulfatase gene serves as an insulator.

Insulator DNAs functionally isolate neighboring genes by blocking interactions between distal cis-regulatory elements and promoters. Here we report that a DNA fragment located in the upstream region of sea urchin, H. pulcherrimus, arylsulfatase (HpArs) gene blocks the interaction of the Ars enhancer when positioned between the enhancer and the target promoter, in an orientation dependent manner. The Ars insulator works only 3' to 5' direction and has no significant stimulatory or inhibitory effects on its own promoter. In transgenic Drosophila, the Ars insulator blocks the interaction between even-skipped stripe enhancer and its target promoter. The insulation mechanism operates also unidirectionally in Drosophila. We also show that the efficiency of transformation of HeLa cells is enhanced when the integrated gene is flanked by the Ars insulator, suggesting the sea urchin insulator overcomes the position-dependent transgene expression in mammalian cells. These results demonstrate that the mechanism of action of the insulator has been conserved throughout evolution.

Animals↗
PubMed1999

[An autopsy case of a bicycle accident with ring fracture at the base of the skull].

We report the autopsy case of a 41-year old passenger who suffered a significant head injury with a typical ring fracture at the base of the skull as a result of a violent fall from a bicycle. Several reports about ring fractures of the base of the skull revealed that they were due to crashing a car at high speed, a collision and/or a fall while riding a motorcycle and a fall in piloting a gyrocopter and so on resulting in severe injury to another part of the body. In this case, the ring fracture occurred when his spine was pushed up by high impact of the parieto-occipital region against the ground.

Accidents, Traffic↗
PubMed1998

Synthesis of peptide aldehyde derivatives as selective inhibitors of human cathepsin L and their inhibitory effect on bone resorption.

Cathepsin L, a lysosomal cysteine protease, is secreted by osteoclasts and participates in bone collagen degradation. In a search for cathepsin L inhibitors as antiosteoporotic agents, a series of peptide aldehyde derivatives were prepared by two synthetic approaches, DMSO oxidation of the corresponding alcohol derivatives and DIBAL-H reduction of the corresponding N, O-dimethylhydroxylamide derivatives, and evaluated for inhibitory activity against human cathepsin L and for inhibitory effects on bone resorption. Some of the peptide aldehyde derivatives including alpha-acylamino aldehyde derivatives showed potent activities. Among these compounds, N-(1-naphthalenylsulfonyl-L-isoleucyl-L-tryptophanal (12) was selected as a candidate for further investigation. Compound 12, a potent, selective, and reversible inhibitor of human cathepsin L with an IC50 of 1.9 nM, inhibited the release of Ca2+ and hydroxyproline from bone in in vitro bone culture system and also prevented bone loss in ovariectomized mice at an oral dose of 50 mg/kg.

Aldehydes↗
PubMed1998

Do all of human midbrain tyrosine hydroxylase neurons synthesize dopamine?

We examined whether all of human midbrain tyrosine hydroxylase (TH) neurons substantially synthesize dopamine (DA) using dual labeling immunohistochemical technique of TH and aromatic L-amino acid decarboxylase (AADC). In the substantia nigra, besides many neurons doubly stained for TH and AADC, neurons stained only for TH and only for AADC (D-neurons [C.B. Jaeger, D.A. Ruggiero, V.R. Albert, T.H. Joh, D.J. Reis, Immunocytochemical localization of aromatic l-amino acid decarboxylase, in: A. Björklund, T. Hökfelt (Eds.), Handbook of Chemical Neuroanatomy, Classical Transmitters in the CNS, Vol. 2, Part 1, Elsevier, Amsterdam, 1984, pp. 387-408.]) were identified. In the ventral tegmental area, dually labeled neurons and TH-only-positive neurons were found. It is indicated that the number of midbrain TH neurons does not reflect the exact number of DA neurons.

Adult↗
PubMed1998

Does tyrosinase exist in neuromelanin-pigmented neurons in the human substantia nigra?

It is controversial whether tyrosinase is involved in the neuromelanin-biosynthetic pathway. We examined tyrosinase-immunoreactivity in human substantia nigra neurons which contain neuromelanin pigments, using antibodies against human tyrosinase and human tyrosine hydroxylase. In human melanoma, the antibody to tyrosinase showed intense immunoreactivity while there was no immunoreactivity with antibody to tyrosine hydroxylase. In the human midbrain pigmented neurons, however, we could detect no tyrosinase-immunoreactivity while the neurons were strongly immunoreactive to tyrosine hydroxylase. The present results suggest that tyrosinase is not involved in the main pathway of neuromelanin biosynthesis.

Adult↗
PubMed1998

The homeobox gene NTH23 of tobacco is expressed in the basal region of leaf primordia.

We reported isolation and characterization of a homeobox gene from tobacco, NTH23. The homeodomain structure of NTH23 was highly homologous to the same regions of class 2 genes of the KN1-type homeobox (sharing more than 85% amino acid identity), but was less similar to class 1 genes of KN1-type. RNA gel blot analysis revealed that NTH23 was expressed in all organs we tested although the gene is primarily expressed in young leaves. To determine more precisely the spatial expression pattern of NTH23 in tobacco, a chimeric NTH23::GUS fusion gene was introduced into tobacco. The signal of GUS activity was observed at the basal part of leaf blade primordia in the NTH23::GUS transgenic tobacco plants. This observation suggests the possibility that NTH23 may be important for the lateral growth of leaf blades.

Amino Acid Sequence↗
PubMed1998

A dopamine-synthesizing cell group demonstrated in the human basal forebrain by dual labeling immunohistochemical technique of tyrosine hydroxylase and aromatic L-amino acid decarboxylase.

The human basal forebrain has been known to contain many neurons immunoreactive (ir) to tyrosine hydroxylase (TH; the first dopamine-synthesizing enzyme). We examined whether these neurons might contain aromatic L-amino acid decarboxylase (AADC; the second step dopamine-synthesizing enzyme) by dual labeling immunohistochemistry and confocal laser-scanning microscopy. Neurons dually-labeled for TH and AADC were found in the anterior olfactory nucleus, olfactory tubercle and the ventral margin of the rostral nucleus accumbens. The examination in the basal forebrain of the macaque monkey also gave substantially the same results. These neurons appear to constitute an independent dopaminergic cell group in the primate basal forebrain.

Adult↗
PubMed1998

BALB/c 3T3 cells co-expressing FGF-2 and soluble FGF receptor acquire tumorigenicity.

The physiological significance of the soluble fibroblast growth factor (FGF) receptors is not clear yet although they are present in blood, vitreous fluid and in the extracellular matrix of vascular endothelial cells. A hypothesis that they might help FGF-2 release from cells is very interesting because FGF-2 does not have clear secretion signal and the mechanism of the secretion of FGF-2 is still unclear. Single overexpression of FGF-2 is related neither to the secretion potential of the molecule nor to the tumorigenicity of the cells. In this report, BALB/c 3T3 cells transformed with the full length of human FGF-2 cDNA are further transformed with the cDNA coding the extracellular domain of human FGF receptor 1. The obtained transformants co-expressing FGF-2 and soluble FGF receptor are highly tumorigenic in nude mice, while the parental cells do not show any tumorigenicity. In the conditioned medium of the double-transformants, FGF-2 is immunologically detected. These results suggest that naturally produced soluble form of FGF receptor supports the release of FGF-2 from the cells and that over-expression of these two molecules leads to induce the malignant tumours in vivo.

3T3 Cells↗
PubMed1998

Intracranial gas on CT after cardiopulmonary resuscitation: 4 cases.

We report four patients in whom gas was seen in the head on CT shortly after cardiopulmonary resuscitation. The gas was in the posterior cranial fossa, presumably within veins, or in the cavernous sinus. The cause of the cardiac arrest was myocardial infarction in three patients and hanging in one. All had peripheral or central venous lines. The mechanism by which gas appeared in the intracranial veins is discussed.

Cardiopulmonary Resuscitation↗
PubMed1998

Vulnerability to aging in the rat serotonergic system.

Distributional changes of serotonergic fibers associated with aging were demonstrated immunohistochemically. Old rat brains were morphologically characterized by the presence of peculiar features of serotonergic fibers not found in the young adult brain. In 24-month-old rats, these aberrant serotonergic fibers were subdivided into two groups according to morphological alterations: type 1 fibers consisting of thin fibers with moderately enlarged varicosities, and type 2 fibers consisting of much thicker fibers that have even larger varicosities and a tortuous course. These two types of fibers were distributed differentially in the forebrain. Type 1 fibers were found mainly in the striatum and frontoparietal cortex, whereas type 2 fibers were found in the posterior cingulate cortex and dentate gyrus of the hippocampal formation. Both types of aberrant fibers were seen in amygdala, frontoparietal cortex, hypothalamus, and thalamus. In 36-month-old rats, more highly degenerating arborizations were detected, and these aberrant ramifications were classified as follows based on shape as: type 3 fibers consisting of highly arborized thin fibers with a larger number of larger varicosities, and type 4 fibers consisting of thick fibers with abundant larger varicosities. Distributional difference indicated that type 1 fibers progress into type 3 fibers, whereas type 2 develop into type 4 fibers. These findings suggest the possibility that one set of pathological fibers emanate from the dorsal raphe nucleus and the other from the median raphe. Moreover, both two sets of serotonergic fibers show age-related aberrations in their morphology over same time course.

Aging↗