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Biomedical subjects

H Hashimoto

Publications and source records attributed to H Hashimoto.

At least 163 records · Page 9Linked to original sources
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↗
PubMed2000

Primary synovial sarcoma of the kidney.

The authors present two cases of primary synovial sarcoma of the kidney. Both patients had a mass in the upper part of the right kidney without any primary extrarenal neoplastic lesions. Grossly, the tumors were soft to rubbery masses measuring 5.5 cm and 5 cm in diameter, respectively. Histologically, both tumors were poorly differentiated synovial sarcoma. The lesions exhibited a hypercellular solid or lobular growth of round, oval, or short spindle cells in variably solid sheets, in intersecting fascicles, or in a haphazard fashion. Areas of solid aggregation or fascicles of the tumor cells alternating with hypocellular myxoid tissues, together with areas displaying a prominent hemangiopericytoma-like pattern, were found. Immunohistochemically, vimentin was diffusely positive and a few tumor cells were positive for cytokeratin, epithelial membrane antigen, and neurofilament. The tumor cells were negative for S- 100 protein, CD34, smooth muscle actin, and desmin, whereas CD56 and CD99 were positive. In both cases, reverse transcription-polymerase chain reaction using ribonucleic acid extracted from formalin-fixed, paraffin-embedded tissues detected SYT-SSX2 fusion gene transcripts, which are characteristic molecular findings of synovial sarcoma. One patient died 10 months after diagnosis. These tumors are unique cases of primary synovial sarcoma of the kidney confirmed by molecular study.

Biomarkers, Tumor↗
PubMed2000

Cardiopulmonary bypass produces greater pulmonary than systemic proinflammatory cytokines.

Cardiopulmonary bypass (CPB) impairs pulmonary endothelial injury in part by increasing expression of adhesion molecules that results in neutrophil influx. Although numerous proinflammatory cytokines up-regulate these responses, the extent to which systemic and pulmonary proinflammatory cytokines increase remains unknown. We therefore examined systemic and pulmonary gene expression and production of proinflammatory cytokines during CPB. Bronchoalveolar lavage and peripheral blood sampling were performed just after the induction of anesthesia and at the end of surgery in 80 patients undergoing CPB. RNA was extracted from harvested cells and cDNA was synthesized by reverse transcription. The expression of interleukin (IL)-6, IL-8, and tumor necrosis factor-alpha (TNF-alpha) was measured by semiquantitative polymerase chain reaction using beta-actin as an internal standard. We also measured these cytokines in cultured alveolar macrophages and plasma monocytes in standard medium alone, or in the presence of lipopolysaccharide. We found 2- to 20-fold increases in gene expression for these cytokines in both plasma and alveolar leukocytes at the end of surgery. However, the increases were 4-8 times greater in alveolar than plasma leukocytes. Alveolar macrophages obtained at the end of surgery produced 1.5-3 times more IL-6, IL-8, and TNF-alpha than those obtained at the beginning (P < 0.0001). Although plasma monocytes produced more IL-8 at the end of surgery (P < 0.001), TNF-alpha and IL-6 did not increase. The production of all cytokines was 1.5-3 times greater in alveolar macrophages obtained at the end of surgery than in plasma monocytes obtained simultaneously (P < 0.005). Our data thus suggest that CPB provokes a greater pulmonary than systemic inflammatory response.

Actins↗
PubMed2000

Neutrophil number and interleukin-8 and elastase concentrations in bronchoalveolar lavage fluid correlate with decreased arterial oxygenation after cardiopulmonary bypass.

Atelectasis is a major cause of decreased arterial oxygenation after cardiopulmonary bypass (CPB). There is a close relationship between atelectasis and inflammatory responses. We therefore tested the hypothesis that neutrophil number and the concentrations of proinflammatory cytokines and elastase in plasma and bronchoalveolar lavage fluid correlate with changes in arterial oxygenation. Bronchoalveolar lavage was performed just after the induction of anesthesia and at the end of surgery in 80 patients undergoing CPB. Peripheral blood was sampled simultaneously. Arterial oxygenation was quantified by PaO(2)/fraction of inspired oxygen (FIO(2)) and intrapulmonary shunt (Q(s)/Q(t)). PaO(2)/FIO(2) and Q(s)/Q(t) decreased significantly at the end of surgery, whereas neutrophil number, interleukin (IL)-6, IL-8, tumor necrosis factor-alpha, and elastase concentrations in the lavage fluid increased significantly. The increase in neutrophil count from the lavage fluid correlated significantly with the increases in IL-8 and elastase concentrations. The increase in neutrophil number and IL-8 and elastase concentrations in the lavage fluid correlated significantly with PaO(2)/FIO(2) and Q(s)/Q(t) at the end of surgery. In contrast, none of the plasma values correlated with these variables. Significant correlation between immune mediators and decreased arterial oxygenation suggests that inflammatory responses in the distal airway are strongly related to a decrease in arterial oxygenation after CPB.

Bronchoalveolar Lavage Fluid↗