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Biomedical subjects

H Hashimoto

Publications and source records attributed to H Hashimoto.

At least 181 records · Page 10Linked to original sources
PubMed2000

The liver in collagen diseases: pathologic study of 160 cases with particular reference to hepatic arteritis, primary biliary cirrhosis, autoimmune hepatitis and nodular regenerative hyperplasia of the liver.

AIMS/BACKGROUND: Among patients with collagen diseases, liver enzyme abnormalities are a relatively common phenomenon. To establish the liver pathology in collagen diseases, detailed pathologic studies were performed on the hepatic diseases in many patients, including various kinds of collagen diseases. METHODS: The livers from 160 patients (120 autopsy and 40 liver biopsy patients) were examined pathologically: 73 with systemic lupus erythematosus (SLE), 32 with rheumatoid arthritis (RA), 18 with polymyositis and dermatomyositis (PM and DM), 15 with systemic sclerosis (SSc), 11 with mixed connective tissue disease (MCTD) and 11 with polyarteritis nodosa (PAN). RESULTS: Liver diseases were divided into three groups: hepatic arteritis, liver diseases associated with collagen diseases (primary biliary cirrhosis, PBC; autoimmune hepatitis, AIH; nodular regenerative hyperplasia of the liver, NRH) and other liver diseases. Hepatic arteritis presenting the features of the PAN type of necrotizing arteritis was found in 27 autopsy patients. The incidence of arteritis in autopsy patients was 100% in PAN and 8.3-25% in other collagen diseases. Primary biliary cirrhosis was observed in 9 patients, 7 of whom (3 with SSc, 2 with RA, 1 with PM and DM, and 1 with MCTD) had antimitochondrial antibodies (AMA)-positive PBC, and 2 SLE patients had AMA-negative PBC. Three patients (2 with SLE and 1 with MCTD) were diagnosed clinicopathologically as having AIH. However, 3 patients (1 with SLE, 1 with MCTD and 1 with PM and DM) with clinical, biochemical and serologic data indicating probable AIH were excluded from the group with AIH association because of the liver histology (no characteristic features of AIH) and clinical course. These results indicated that data without histologic assessments of the liver are not adequate for diagnosing AIH in collagen diseases. Nodular regenerative hyperplasia of the liver was observed in 7 patients (5 with SLE, 1 with SSc and 1 with PAN). CONCLUSION: The present study offers data that are useful for the diagnosis and treatment of patients with collagen diseases and liver abnormalities.

Adolescent↗
PubMed2000

Postsynaptic 5-hydroxytryptamine(1A) receptor activation increases in vivo dopamine release in rat prefrontal cortex.

5-Hydroxytryptamine (5-HT) plays a role in the regulation of 3, 4-dihydroxyphenylethylamine (dopamine) neurons in the brain, but the precise mechanism of regulation by 5-HT(1A) receptors of dopamine release has not been defined. The present study describes the effect of 5-¿3-[[(2S)-1,4-benzodioxan-2ylmethyl]amino]propoxy¿-1, 3-benzodioxole HCl (MKC-242), a highly potent and selective 5-HT(1A) receptor agonist, on dopamine release in the prefrontal cortex using microdialysis in the freely moving rat. Subcutaneous injection of MKC-242 (0.3 - 1.0 mg kg(-1)) increased extracellular levels of dopamine in the prefrontal cortex. The effect of MKC-242 in the prefrontal cortex was antagonized by pretreatment with the selective 5-HT(1A) receptor antagonist, N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl)cyclohe xanecarboxamide (WAY100635; 1 mg kg(-1), i.p.). Local application of WAY100635 (10 microM) via a microdialysis probe antagonized the effect of systemic MKC-242 in an increasing dopamine release, and locally infused 8-hydroxy-2-(di-n-propylamino)tetralin (10 microM) increased dopamine release in the prefrontal cortex. MKC-242 increased cortical dopamine release in the rats pretreated with 5, 7-dihydroxytryptamine (150 microgram, i.c.v.) that caused an almost complete reduction in cortical 5-HT content. The effect of MKC-242 to increase dopamine release was also observed in the hippocampus, but not in the striatum or nucleus accumbens. Fluoxetine, a selective serotonin reuptake inhibitor, increased dopamine release in the prefrontal cortex, but not in the nucleus accumbens, while buspirone, a 5-HT(1A) receptor agonist, increased dopamine release in both brain regions. The present results indicate that activation of postsynaptic 5-HT(1A) receptors increases dopamine release in a brain region-specific manner.

5,7-Dihydroxytryptamine↗
PubMed2000

Inhibitory mechanism of tranilast in human coronary artery smooth muscle cells proliferation, due to blockade of PDGF-BB-receptors.

We have previously reported that tranilast, an anti-allergic drug, prevented the experimental intimal thickening in the rat and mouse femoral arteries and its effect may be exerted through the inhibition of vascular smooth muscle cell proliferation. However, its inhibitory mechanism has yet to be understood. In this study, we investigated the inhibitory effect of tranilast on platelet-derived growth factor BB-homodimer (PDGF-BB) mediated signal transduction pathways in cultured human coronary artery smooth muscle cells (CASMCs). Growth responses to PDGF-BB were measured by [(3)H]-thymidine incorporation or cell counting. Activation of DNA synthesis and augmentation of cell proliferation stimulated by PDGF-BB in quiescent cultures of CASMCs were inhibited by tranilast in a concentration-dependent manner. Western blot analysis of lysates from CASMCs with an anti-activated mitogen-activated protein (MAP) kinase antibody revealed that tranilast (10 - 300 microM) inhibited MAP kinase activation by PDGF-BB in a concentration-dependent manner. Tranilast also reduced PDGF-BB-stimulated tyrosine phosphorylation of a 180 kDa band, corresponding in mass to the PDGF beta-receptor, as shown by immunoblots using an anti-phosphotyrosine antibody. Receptor-binding study with [(125)I]-PDGF-BB on CASMCs showed that tranilast (10 - 1000 microM) inhibited the specific binding of PDGF-BB to cell surface receptors in a concentration-dependent manner. Scatchard analysis revealed that pretreatment with 300 microM tranilast decreased the maximum binding capacity (B(max)) from 27.6 to 18.0 fmol 10(6) cells(-1) without affecting binding affinity (K(d) approximately 0.15 nM), indicating a non-competitive inhibition of the receptor binding. These results suggest that the suppression of human CASMC growth by tranilast might be at least partly due to blockade of PDGF-BB-receptor binding.

Animals↗
PubMed2000

Rhabdoid tumour of the lung is a dedifferentiated phenotype of pulmonary adenocarcinoma.

AIMS: Primary rhabdoid tumour of the lung is rare, and histological and biological characteristics have not been fully documented. We describe three cases of primary lung rhabdoid tumour, all associated with adenocarcinoma, and investigate the histological features and biological characteristics. METHODS AND RESULTS: Three cases were obtained from a total 902 cases of surgically removed primary lung tumours between 1986 and 1998. The rhabdoid cells were found to occupy about 50-90% of each tumour. All of the tumours had nonrhabdoid adenocarcinoma foci in the centre of the tumours. Transition between the adenocarcinomatous and rhabdoid components was demonstrated. Detailed immunohistochemical studies were carried out. The epithelial markers, cytokeratins and epithelial membrane antigen (EMA), were strongly expressed in rhabdoid and adenocarcinomatous components. Furthermore, surfactant apoprotein A was positive in both components in one case, but myoglobin, MyoD and HHF35 were not expressed. Vimentin was strongly and diffusely stained in all cases. The neuroendocrine markers, chromogranin A (all cases), neuron-specific antigen (NSE) (two cases) and CD56 (one case) were occasionally positive in only a small number of the rhabdoid tumour cells. GM-CSF was positively stained in one case, and the dedifferentiated characteristics of the rhabdoid cells was suggested. Proliferative cell nuclear antigen (PCNA) was strongly demonstrated in the rhabdoid tumour cells (all cases). To gain better understanding the highly proliferative characteristics of the tumours, p53 gene (exons 5-8) mutation was examined by DNA sequencing analysis; mutation of the p53 DNA was not detected. Overexpression of p53 protein was also not demonstrated in all cases. HPV6 was demonstrated in one case by PCR method and also non-isotopic in-situ hybridization (NISH). Two cases died in a short period of time (3 years and 4 months, respectively). CONCLUSION: The rhabdoid cells in these three cases were considered to represent the dedifferentiated components of the accompanying adenocarcinoma. Dedifferentiated characteristics (neuroendocrine markers, GM-CSF, vimentin, and the aggressive behaviour) were evident.

Adenocarcinoma↗
PubMed2000

Identification of a nuclear export signal in MKK6, an activator of the carp p38 mitogen-activated protein kinases.

Carp homologues of p38 mitogen-activated protein kinase (MAPK) and its activator MAPK kinase 6 (MAPKK6, referred to as MKK6) were identified. There exist at least two distinct carp p38s, cp38a and cp38b, both of which consist of 361 amino acids. The transcript of c38a was exclusively expressed in the ovary, whereas that of cp38b was ubiquitously expressed. Western blot analysis with anti-(phosphorylated MAPK) Ig specific to the active p38 or JNK has shown that p38 was activated in response to hypertonic stress (1 M sorbitol) in epithelioma papilosum cyprini carp epithelial cells (EPC) and that the activation of p38 proceeded faster to the maximal level than that of JNK. Carp homologue (cMKK6) of p38 activator MKK6 consists of 404 amino acids. It was expressed ubiquitously but was most abundant in the ovary. An in vitro kinase assay demonstrated that cMKK6 is an upstream activator of cp38 and cp38b in carp because it specifically phosphorylated and activated cp38a and cp38b. Interestingly, we found that cMKK6 has a nuclear export signal (NES) sequence in its N-terminal region although upstream activators of stress-activated MAPKs, p38 and JNK, do not in other animals. The NES sequence facilitated nuclear export of cMKK6 and ovalbumin. Leucine residues in the sequence were crucial for the NES activity, as the activity was lost on replacement of the leucines to alanines. The existence of an NES in cMKK6 implies the requisite of strict regulation of the p38 MAPK pathway in carp. The abundance of these components for the stress-activated pathway in the ovary might be related to ectogenetic early development.

Amino Acid Sequence↗
PubMed2000

Synovial sarcomas of three children in the first decade: clinicopathological and molecular findings.

Synovial sarcoma in children below the age of 10 years is rare. We report on three cases of synovial sarcoma which were diagnosed in three children aged 3, 8 and 8 years, respectively. These tumors were located in the hip of the 8-year-old, the foot of the 3-year-old, and the elbow of the other 8-year-old. Histologically, one tumor was a biphasic synovial sarcoma, and the other two, which had been initially diagnosed as infantile fibrosarcoma, were of the monophasic fibrous type. In the three cases, a reverse transcription-polymerase chain reaction (RT-PCR) using ribonucleic acid extracted from formalin-fixed, paraffin-embedded tissues detected SYT-SSX1 fusion gene transcripts resulting from translocation t(X;18)(p11.2;q11.2), which is specific for synovial sarcoma. ETV6-NTRK3 fusion gene transcripts that result from t(12;15)(p13;q25), which is characteristic of congenital/infantile fibrosarcoma, were not demonstrated. In conclusion, other pediatric soft tissue sarcomas, such as congenital/infantile fibrosarcoma, spindle cell rhabdomyosarcoma, leiomyosarcoma and malignant peripheral nerve sheath tumor, should be distinguished from synovial sarcoma in children, especially the monophasic fibrous type. RT-PCR analysis is a useful approach to the final diagnosis of synovial sarcoma arising at such an early age.

Base Sequence↗
PubMed2000

Roles of p53 and MDM2 in tumor proliferation and determination of the prognosis of transitional cell carcinoma of the renal pelvis and ureter.

BACKGROUND: The significance of p53 overexpression for the prognosis of transitional cell carcinoma (TCC) of the renal pelvis and ureter remains controversial. Simultaneous evaluation of p53 and MDM2 may enable better prediction of tumor proliferation and patient prognosis than that obtained with evaluation of p53 alone. METHODS: Immunohistochemical detection of p53 protein, MDM2 protein and Ki-67 antigen as proliferation markers was performed for tissue samples obtained from 74 patients with TCC of the renal pelvis and ureter. The correlations of p53/MDM2 overexpression with conventional pathological features, Ki-67 labelling index (LI) and patient survival were studied. RESULTS: Overexpression of p53 was related to progression of each of the pathological features examined (grade, stage, type of infiltration, vascular invasion and lymphatic invasion) and Ki-67 LI was significantly higher with high p53 expression than with low p53 expression. However, overexpression of MDM2 was related to neither disease progression nor Ki-67 LI. Survival analyses were performed for 66 patients. Univariate analysis showed p53 to be a useful prognostic indicator, but in a multivariate analysis only type of infiltration and Ki-67 LI were independent survival markers, while p53 was not. Overexpression of MDM2 was unrelated to patient survival, and the combination of p53 and MDM2 for survival indication was found not to be useful. CONCLUSIONS: Overexpression of p53 is related to disease progression, increased tumor proliferation and patient survival for TCC of the renal pelvis and ureter, but the independent prognostic value of p53 did not reach statistical significance. Combined analysis of MDM2 with p53 cannot be recommended for examination of the malignant potential of TCC of the renal pelvis and ureter.

Adult↗
PubMed2000

Mice with markedly reduced PACAP (PAC(1)) receptor expression by targeted deletion of the signal peptide.

In an attempt to study the pituitary adenylate cyclase-activating polypeptide (PACAP) type 1 (PAC(1)) receptor (PAC(1)R) function in vivo and to produce a mouse model with altered expression of PAC(1)R, we have used gene targeting in embryonic stem cells to disrupt exon 2 of the PAC(1)R gene, which contains the ATG translation start site and the signal peptide. Un-expectedly, active transcription of PAC(1)R mRNA was detected in the mutant mice; however, exon 1 was spliced to exon 3 (skipping exon 2), and (125)I-PACAP27 binding in brain was greatly reduced. PAC(1)R exon 2(-/-) mice were viable, fertile, and morphologically and histologically indistinguishable from their wild-type counterparts. We next examined the ligand binding and cell surface expression of the mutant receptor lacking the signal peptide in transfected COS-7 cells. (125)I-PACAP27 binding of the mutant receptor was approximately one-tenth of that in the wild-type receptor. Although the wild-type receptor was expressed abundantly in both the plasma membrane and the cytoplasm around the nucleus, the mutant receptor was expressed in the plasma membrane with a markedly reduced level. Digestion of the membranes with endoglycosidase F greatly reduced the size of the wild-type receptor but only slightly reduced that of the mutant receptor. These results demonstrate that the signal peptide is required for efficient cell surface expression and N-linked glycosylation of the PAC(1)R. However, the mutant receptors still functionally coupled to adenylate cyclase in COS-7 cells, suggesting the presence of sufficient spare receptors such that the mutant receptors are capable of activating the second messenger system. We suggest that the mutant mice with markedly reduced PAC(1)R expression can serve as a useful animal model or cell culture system for further studies in PAC(1)R function.

Animals↗
PubMed2000

Synergistic induction of pituitary adenylate cyclase-activating polypeptide (PACAP) gene expression by nerve growth factor and PACAP in PC12 cells.

Pituitary adenylate cyclase-activating polypeptide (PACAP) gene expression was analyzed in PC12 cells. PC12 cells transfected with a PACAP promoter-luciferase reporter construct were utilized to investigate the effects of PACAP, either alone or in combination with nerve growth factor (NGF), on PACAP transcriptional response. PACAP induced transcription from the PACAP promoter through PACAP type I receptor (PAC1 receptor). PACAP gene transcription was also induced by NGF. Simultaneous treatment with PACAP and NGF resulted in a synergistic transcriptional response that was more than three times the predicted response, based on a simple additive effect of both agents. This synergism in transcriptional response paralleled the PACAP mRNA levels, as determined by RT-PCR and northern blotting. The level of PACAP mRNA peaked 3 h after stimulation and gradually returned to basal levels by 48 h. PC12 cells are known to express predominantly the hop isoform of the PAC1 receptor, which positively couples to both adenylate cyclase and phospholipase C. To determine the role of the cyclic AMP and protein kinase C pathways in PACAP gene expression, the effects of forskolin and phorbol 12-myristate 13-acetate (PMA) were then examined. PMA did not alter PACAP mRNA levels but enhanced forskolin-induced PACAP mRNA expression. Down-regulation of protein kinase C blocked the ability of PACAP to stimulate PACAP mRNA expression. The mitogen-activated protein kinase extracellular signal-regulated kinase (ERK) kinase 1/2 (MEK1/2) inhibitor PD98059 also blocked the PACAP mRNA expression induced by either PACAP or NGF but not that induced by a combination of PACAP and NGF. These results suggest that PACAP stimulates the PACAP gene expression in PC12 cells at least in part through activation of adenylate cyclase and protein kinase C signaling pathways and that the ERK1/2 cascade is involved in PACAP and NGF-induced PACAP gene expression, although redundant signaling pathways may also be involved. The present finding showing that PACAP in combination with NGF causes a synergistic increase in PACAP gene expression in PC12 cells supports the idea that PACAP acts as an autocrine regulatory factor.

Animals↗
PubMed2000

Totally implantable ventricular assist system that can increase brain blood flow.

In the clinical usage of the ventricular assist device (VAD), multiple organ failure becomes an important problem. To improve the clinical record of the VAD, another organ function may be vitally important. For that reason, we have been developing a VAD system aiming at improving another organ's function. Development of the vibrating flow pump (VFP), which can generate a very unique flow pattern from 10 Hz to 50 Hz, was ongoing in our Institute. In order to evaluate brain blood flow and oxygen consumption, HbO2 was measured with a NIRO monitoring device in healthy adult goats. Four goats were anesthetized with halothane inhalation; then left thoracotomy was performed for the left heart bypass. HbO2 of the brain was measured by recording of the hemodynamic variables during left heart assistance with the VFP system. During left heart bypass with the VFP system, hemodynamic parameters stayed within normal range, and satisfactory pump output was easily obtained. Pump output stayed within 20-40% bypass to evaluate the effect of high frequency oscillated assist flow on brain blood flow during the same cardiac output. Interesting results were observed during the experiments. During 30 Hz drive of the VFP left heart assistance, HbO2 suggested that brain blood flow significantly increased compared with another drive frequency assistance during the same total cardiac output. These results suggest that we can control the brain blood flow with a totally implantable VAD system such as the VFP system.

Animals↗
PubMed2000

Spinal dural arteriovenous fistula with perimesencephalic subarachnoid haemorrhage.

A case is reported of a 66 year old woman presenting with perimesencephalic subarachnoid haemorrhage (SAH) which was caused by a spinal dural arteriovenous fistula at the C1 level. The fistula drained into the venous system of the posterior cranial fossa through a perimedullary vein. The bleeding was thought to result from venous hypertension induced by the fistula. This case may support the hypothesis that perimesencephalic non-aneurysmal SAH can be ascribed to venous bleeding and that venous hypertension is the key to its pathology.

Aged↗
PubMed2000

Surgical management of cerebral arteriovenous malformations with intraoperative digital subtraction angiography.

Complete excision of cerebral arteriovenous malformations (AVMs) is requisite to improving the outcome of patients with AVMs. Five patients with a small or medium cerebral AVM underwent surgery with an intraoperative digital subtraction angiography (DSA) unit. There were no residual AVMs and no complications in the examination of intraoperative DSA. The findings of postoperative angiography were consistent with those of intraoperative DSA. Intraoperative DSA provided the benefits of not only identification of a feeding artery, but also recognition of the complete excision during surgery.

Adolescent↗
PubMed2000

Impairment of mycophenolate mofetil absorption by iron ion.

OBJECTIVE: We sought to evaluate the effect of iron ion on the absorption of mycophenolate mofetil, which is an immunosuppressive agent. The pharmacokinetics of mycophenolic acid were studied. METHODS: A randomized crossover design with two phases was used. A 7-day washout period separated the two treatment conditions. In the first phase, the volunteers received 1.0 g of mycophenolate mofetil alone (study 1); in the second phase, the volunteers received 1.0 g of mycophenolate mofetil and 2 tablets of iron ion preparations concomitantly (study 2). The serum concentration of mycophenolic acid, which is a pharmacologically active metabolite, was measured by reverse-phase HPLC. RESULTS: The area under the plasma concentration-time curve from 0 to 12 hours and the maximum concentration of mycophenolic acid in study 2 were significantly less than in study 1 (area under the curve, 32.9 +/- 14.7 versus 2.92 +/- 0.883 microg x h/mL, P < .001, maximum concentration, 20.1 +/- 9.21 versus 1.30 +/- 0.367 microg x h/mL, P < .001). CONCLUSIONS: This finding shows that when mycophenolate mofetil and iron ion preparations were administered concomitantly, a remarkable decrease of mycophenolate mofetil absorption was observed. Therefore it seems to be clear that we must avoid the concomitant administration of mycophenolate mofetil and iron ion preparations.

Adult↗
PubMed2000

Image contrast of ultra HVEM and future ultra HREM

Review of the measurements and interpretation of energy dependence of extinction distance and transmissive power of electrons, which have appeared in the electron microscope images of crystals at the voltages ranging from 50 to 3000 kV, is presented. Applications of two beam dynamical theory of electron diffraction considering absorption effect of electrons made clear the importance of relativistic effect of the mass of electron to the variation of extinction distance and transmissive power at higher voltage and noted that they are proportional to (v/c) and (v/c)2 respectively, where v and c are the velocity of illuminating electrons and light. With elevating accelerating voltage of illuminating electrons, it was noted that many diffracted waves are excited and thus, for understanding of the image contrast and the improvement of transmissive power of electrons, many beam dynamical theory considering absorption of electron waves has to be applied. Detailed analysis of the excitation and absorption of component Bloch waves was carried out and flux (electron current) flow of Bloch waves and total waves was deduced. Improvements of image contrast and visibility of the imperfection in crystalline materials both in thin and thick regions of ultra-high voltages were realized by using the multi-beam imaging (MBI) method. In MBI of very thick crystals, it was noted that most of the inelastically scattered electrons which appeared in the background of the diffraction patterns contribute to the image contrast by the successive elastic scattering after inelastic scattering. It was noted that the improvement of maximum usable thickness at high voltage is highly dependent on the contribution of inelastically scattered electrons. The calculated flux flows of total electrons of various materials in various orientations were calculated for not only ultra-high voltages but low voltages such as 100 kV. It was suggested that the intensity distribution of such flux flow will be recorded by the ultra HREM in the near future and will become useful to identify types of atoms, such as the interface consisting of different kinds of atoms.

Journal Article↗
PubMed2000

Morphology and structure of various phases at the bonding interface of Al/steel formed by explosive welding

The bonding interface of explosively-welded aluminium and steel in three explosive conditions have been investigated by using scanning electron microscopy, transmission electron microscopy, electron diffraction and electron probe microanalysis methods. The results show that all the interfaces have the shape of waves with curled front formed by process of superplasticity and some discontinuous reacted zones. They consist of amorphous and nano sized crystals and quasi-crystals as well as the compounds such as AlFe, Al2Fe, Al3Fe and Al6Fe with various shapes. The basal steel crystal near the interface has structure of martensite and perlite crystals which are deformed by the process of superplasticity. The size of reacted zone becomes large with increasing amount of explosive charge powder and separation of the driver Al plate from the basal steel plate.

Journal Article↗