[Gene-immunotherapy using dendritic cells].
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Biomedical subjects
Publications and source records attributed to T Ishida.
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OBJECTIVE: We assess the usefulness of microwave hepatic tumor coagulation therapy with balloon occlusion of segmental hepatic blood flow for eight recurrent metastatic hepatic tumors in seven patients. CONCLUSION: Limited early experience with microwave hepatic tumor coagulation therapy and segmental hepatic blood flow occlusion has been positive, suggesting that further clinical evaluation is warranted.
OBJECTIVE: We developed a new method to distinguish between various interstitial lung diseases that uses an artificial neural network. This network is based on features extracted from chest radiographs and clinical parameters. The aim of our study was to evaluate the effect of the output from the artificial neural network on radiologists' diagnostic accuracy. MATERIALS AND METHODS: The artificial neural network was designed to differentiate among 11 interstitial lung diseases using 10 clinical parameters and 16 radiologic findings. Thirty-three clinical cases (three cases for each lung disease) were selected. In the observer test, chest radiographs were viewed by eight radiologists (four attending physicians and four residents) with and without network output, which indicated the likelihood of each of the 11 possible diagnoses in each case. The radiologists' performance in distinguishing among the 11 interstitial lung diseases was evaluated by receiver operating characteristic (ROC) analysis with a continuous rating scale. RESULTS: When chest radiographs were viewed in conjunction with network output, a statistically significant improvement in diagnostic accuracy was achieved (p < .0001). The average area under the ROC curve was .826 without network output and .911 with network output. CONCLUSION: An artificial neural network can provide a useful "second opinion" to assist radiologists in the differential diagnosis of interstitial lung disease using chest radiographs.
An excessive production of extracellular matrix (ECM) proteins in glomerular mesangial cells is considered to be responsible for the development of mesangial expansion seen in diabetic nephropathy. Mechanical stretch due to glomerular hypertension has been proposed as one of the factors leading to an increase in the production of ECM proteins in mesangial cells, but the precise mechanism of stretch-induced overproduction of ECM proteins has not been elucidated. Herein, we provide the evidence that mitogen-activated protein kinase (MAPK) may play a key role in the overproduction of fibronectin (FN) in mesangial cells exposed to mechanical stretch. MAPK, also termed extracellular signal-regulated kinase (ERK) and c-Jun NH2-terminal kinase (JNK), was activated by mechanical stretch in time- and intensity-dependent manners. Stretch-induced activation of ERK was inhibited by herbimycin A, a tyrosine kinase inhibitor, but not by GF109203X or calphostin C, the inhibitors of protein kinase C. Mechanical stretch also enhanced DNA-binding activity of AP-1, and this enhancement was inhibited by PD98059, an inhibitor of MAPK or ERK kinase (MEK). Furthermore, mechanical stretch stimulated the expression of FN mRNA followed by a significant increase in its protein accumulation. PD98059 could prevent stretch-induced increase in the expression of FN mRNA and protein. These results indicate that the activation of ERK may mediate the overproduction of ECM proteins in mesangial cells exposed to mechanical stretch, an in vitro model for glomerular hypertension seen in diabetes.
The present study was designed to examine whether a serial force pattern in the finger-tapping sequences was retained and adaptively controlled. On practice trials, 15 male college students tapped a force plate connected to strain gauges which provided feedback. On test trials, subjects recalled the force pattern and the intertap interval acquired during practice without feedback (recalled task). Next, subjects adaptively tapped the acquired force pattern at the half (speeded task) and twice the intertap interval acquired during practice (slowed task). Analysis showed that the force patterns were quite precisely retained across tasks, and the relative force pattern was retained. Although there was no difference for force between the slowed and the recalled task, the force in the speeded task differed from that in the recalled task. This indicated that changing to a fast pace creates a more difficult adaptive task than changing to a slow pace.
We report five cases of purple urine bag syndrome (PUBS). All the patients were women and they had been bed-ridden for a long period due to cerebrovascular diseases. They tended to be constipated as a result of habitual use of laxatives. Indicanuria was proven in the all urinary samples from the patients. The four assessable urinary cultures showed Proteus mirabilis contamination. Total days without evacuation per month in patients with PUBS and control subjects (5 catheterized subjects without PUBS) were 16.5 +/- 3.7 and 6.8 +/- 4.8, respectively (mean +/- SD), showing a significant difference (p < 0.05). In each case, this syndrome was not considered to have affected their clinical course. We concluded that it is unnecessary to treat patients with PUBS aggressively. Control of evacuation and urological sanitation are important in these patients.
PURPOSE: Nerve growth factor (NGF) is synthesized in the target organs innervated by autonomic and sensory nerves so as to grow, maintain and/or repair the neurons. The present study evaluated the effects of ischemia on NGF synthesis and voiding function of the rat urinary bladder. MATERIALS AND METHODS: Bladder ischemia was induced by ligating of bilateral internal iliac arteries in the female rats. We examined the changes in the blood flow, histological structure, voiding function and NGF content of the bladder immediately, 1, 7, 14 and 28 days after the surgery. Blood flow was estimated by measuring absorbance of homogenized bladder tissue after dye injection into the abdominal aorta. Voiding function was assessed by continuous cystometry under an awake restrained condition. NGF was quantified by enzyme immunoassay (ELISA method). RESULTS: Blood flow decreased to 18% of the control immediately after the vascular ligation, and gradually recovered to 66% of the control on day 28. Histologically, epithelial ablation and thinning of muscle layer were observed on days 1 and 7. These histological disorders gradually improved to normal appearance on day 14. On day 1, while the maximum contraction pressure significantly decreased, the contraction frequency and small prevoiding contraction increased. On the other hand, the voiding efficacy markedly decreased on day 7. These functional changes recovered nearly to the control levels after day 14. NGF content transiently increased 2.4 times as the control on day 1. CONCLUSION: The present results will indicate that the voiding function deteriorated by acute ischemia is temporarily compensated by detrusor hyperrefrexia, which may be attributable to an enhanced NGF synthesis, and then improves by the development of collateral blood circulation.
The present study was addressed on the effect of 3,3',4,4',5-pentachlorobiphenyl (PenCB) to the expression of glucose regulated protein (GRP) 78 and GRP94 in liver endoplasmic reticulum of rat by treatment with the schedule after acute or subacute exposure. In the acute exposure, male Wistar rats received PenCB in corn oil at once a dose of 25 mg/kg i.p., then at 5 days after treatment the microsomes were prepared. Free- and pair-fed control groups were given the vehicle. The microsomal proteins were separated on SDS-PAGE, transferred to membrane and blotted using anti-sera to the GRPs. The reduction of GRP78 and GRP94 was associated significantly with the acute exposure. In subacute exposure, the rats received PenCB in corn oil at once a dose of 0.1 or 1.0 mg/kg i.p. At 4 weeks after treatment, liver microsomes were obtained. The expression level of GRP78 and GRP94 are also decreased at 1.0 mg PenCB/kg treatment as similar as the acute exposure. But the reduction was not notable at 0.1 mg PenCB/kg treatment. GRP78 and GRP94 are a member of GRPs and the expression is regulated by glucose in cells as stress proteins. GRP78 and GRP94 have also the function for chaperone protein. Chaperone proteins have important physiological functions against synthesized and/or denatured proteins, which include assembling, folding of proteins. Our results suggested that a part of the toxicity of PenCB is associated to significant decrease of the chaperone proteins in the endoplasmic reticulum.
We report here that a highly toxic coplanar polychlorinated biphenyl (PCB), 3,3',4,4',5-pentachlorobiphenyl (PenCB) induces molecular chaperones, HSP70 and HSP90 in liver cytosol of rats. Male Wistar rats received PenCB in corn oil once at a dose of 25 mg/kg i.p. Pair-fed control groups were treated with the vehicle and given the amount of chow matched with that taken by the PenCB-treated animals, and free-fed controls were given the vehicle. The liver cytosolic HSP70 level in rats treated with PenCB was 5-fold higher than those in free-fed controls, though that for pair-fed controls was approximately 2-fold higher than that in free-fed controls. The liver cytosolic HSP90 alpha and HSP90 beta levels were also higher in PenCB-treated rats than in both control groups, but the induction extent was lesser than that for HSP70. Inductive effect on the chaperones was examined with a single different dose of PenCB 0, 0.5, 1.0, 5.0, 10 and 25 mg/kg. Marked induction of the HSP70 level was observed with a minimum dose of PenCB 0.5 mg/kg. The HSP90 alpha level was induced with PenCB-dose dependent manner although the HSP90 beta induction was greatest with a dose of PenCB 5.0 mg/kg. HSP70 and HSP90 are essential for cells under normal conditions and act as molecular chaperones. HSP90 is well known to modulate the function of sex steroid hormone or aromatic hydrocarbon receptors while HSP70 is required for receptor-HSP90 heterocomplex assembly. The role of molecular chaperones may be involved in the endocrine disrupting properties of coplanar PCB and dioxins.
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Inadequate function of dendritic cells (DCs) in tumor-bearing hosts is one mechanism of tumor escape from immune system control and may compromise the efficacy of cancer immunotherapy. Vascular endothelial growth factor (VEGF), produced by most tumors, not only plays an important role in tumor angiogenesis but also can inhibit the maturation of DCs from hematopoietic progenitors. Here, we investigate a novel combination of antiangiogenic and immunotherapy based on this dual role of VEGF. Two s.c. mouse tumor models were used: D459 cells, expressing mutant human p53; and MethA sarcoma with point mutations in the endogenous murine p53 gene. Therapy with anti-mouse VEGF antibody (10 microg i.p. twice a week over 4 weeks) was initiated when tumors became palpable. Treatment of established tumors with anti-VEGF antibody alone did not affect the rate of tumor growth. However, anti-VEGF antibody significantly improved the number and function of lymph node and spleen DCs in these tumor-bearing animals. To investigate the possible effects of this antibody on the immunotherapy of established tumors, tumor-bearing mice were immunized with DCs pulsed with the corresponding mutation-specific p53 peptides, together with injections of anti-VEGF antibody. Therapy with peptide-pulsed DCs alone resulted in considerable slowing of tumor growth but only during the period of treatment, and tumor growth resumed after the end of the therapy. Combined treatment with peptide-pulsed DCs and anti-VEGF antibody resulted in a prolonged and much more pronounced antitumor effect. This effect was associated with the induction of significant anti-p53 CTL responses only in this group of mice. These data suggest that inhibition of VEGF may be a valuable adjuvant in the immunotherapy of cancer.
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BACKGROUND: The limited exposure typical of new minimally invasive surgical approaches to cardiac surgery makes it difficult to utilize traditional equipment such as temporary pacing electrodes or the placement of drainage tubes into the lateral pleural space. To overcome these difficulties, we have developed specialized drainage tubes just for limited access cardiac surgery. METHODS: The first device is a drainage tube with temporary pacing function. It has three fixed electrodes and one free pacing wire incorporated into an elliptical, angled 28 Fr silicone drainage tube. This tube is placed in the space between the heart and the diaphragm. The two fixed electrodes provide epicardial contact for ventricular pacing. The third fixed electrode and one free pacing wire are for the purpose of atrial pacing (Japanese patent #2,701,135). The second device is a Y-shaped drainage tube. Frequently, the pleural space is opened during harvesting of an internal mammary graft and then insertion of a chest tube in the thoracic cavity becomes necessary. We developed a new Y-shaped tube where one segment is placed in the retrosternal space and one segment is placed in the pleural cavity. (Japanese Association of Intellectual Copyright #130,591) RESULTS: The drainage-pacing device was used in 48 coronary artery bypass grafting (CABG) patients. Drainage function and pacing function were excellent in all patients. The bifurcated drainage device was used in 34 patients achieving effective drainage of both cavities without complication during or after removal. CONCLUSIONS: Due to the limited surgical exposure provided by the newer minimally invasive procedures in cardiac surgery, specialized equipment that can be inserted through small incisions needs to be developed. We report the development of a new drainage-pacing device as well as a bifurcated drain for simultaneous drainage of the mediastinal and pleural cavities. These devices have facilitated minimally invasive cases and were free of complications.
Nitric oxide (NO), constitutively produced by endothelial nitric oxide synthase (eNOS), plays a major role in the regulation of blood pressure and vascular tone. We generated transgenic mice overexpressing bovine eNOS in the vascular wall using murine preproendothelin-1 promoter. In transgenic lineages with three to eight transgene copies, bovine eNOS-specific mRNA, protein expression in the particulate fractions, and calcium-dependent NOS activity were confirmed by RNase protection assay, immunoblotting, and L-arginine/citrulline conversion. Immunohistochemical studies revealed that eNOS protein was predominantly localized in the endothelial cells of aorta, heart, and lung. Blood pressure was significantly lower in eNOS-overexpressing mice than in control littermates. In the transgenic aorta, basal NO release (estimated by Nomega-nitro-L-arginine-induced facilitation of the contraction by prostaglandin F2alpha) and basal cGMP levels (measured by enzyme immunoassay) were significantly increased. In contrast, relaxations of transgenic aorta in response to acetylcholine and sodium nitroprusside were significantly attenuated, and the reduced vascular reactivity was associated with reduced response of cGMP elevation to these agents as compared with control aortas. Thus, our novel mouse model of chronic eNOS overexpression demonstrates that, in addition to the essential role of eNOS in blood pressure regulation, tonic NO release by eNOS in the endothelium induces the reduced vascular reactivity to NO-mediated vasodilators, providing several insights into the pathogenesis of nitrate tolerance.