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Biomedical subjects

M Kitamura

Publications and source records attributed to M Kitamura.

At least 361 records · Page 20Linked to original sources

Reevaluation of the two-component hypothesis for turning behaviour by manipulating activities in the striatum and the nucleus accumbens of intact rats.

The role of dopamine D1 and D2 receptor stimulation in the production of turning behaviour in rats was studied. In rats pretreated with unilateral injections of the non-selective dopamine D1/D2 receptor antagonist, cis(Z)-flupentixol (10 micrograms/0.5 microliter), into the ventral striatum, quinpirole (1, 3, 5, 10 mg/kg i.p.), a selective dopamine D2 receptor agonist, induced dose-dependent turning behaviour, while SKF 38393 (1, 3, 5, 10 mg/kg i.p.), a selective dopamine D1 receptor agonist, did not. The effect of the two drugs together was much greater than the effect of quinpirole alone and was reduced by additional blockade of dopamine D1/D2 receptors in either the ipsilateral or contralateral nucleus accumbens. The role of the nucleus accumbens in turning behaviour was determined from the effects of unilateral injections of SKF 38393 and quinpirole into the nucleus accumbens. The results show that unilateral injections of a mixture of the two drugs (SKF 38393 5 micrograms + quinpirole 10 micrograms/0.5 microliter) into the nucleus accumbens produced turning while injections of single drugs did not. Turning was abolished by the blockade of dopamine D1/D2 receptors in the ipsilateral but not contralateral ventral striatum. Turning was also reduced by the blockade of the contralateral nucleus accumbens. Moreover, turning was not produced by injections of the drug mixture into the dorsal or ventral striatum.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

Rhabdomyosarcoma arising in transgenic mice harboring the beta-globin locus control region fused with simian virus 40 large T antigen gene.

The beta-globin locus control region (LCR) confers a high level of erythroid-specific and copy-number-dependent expression to human globin genes in transgenic mice. Simian virus 40 T (tumor) antigen (Tag) with its own natural enhancer causes choroid plexus tumors in mice. We investigated the effect of the LCR on Tag gene expression, reasoning that mice harboring a LCR-Tag fusion gene might develop hematopoietic malignancies. To test this hypothesis we introduced an enhancerless Tag gene downstream of a LCR cassette into the germ lines of mice. The phenotypes of the transgenic mice depended on the copy number of the transgene. While mice with 1-2 copies matured normally, those with 3-7 copies developed rhabdomyosarcomas in different anatomic sites at high frequency and showed hyperplasia of the pancreatic islet cells which progressed to pancreatic islet tumors. In addition, the mice bearing 7 copies of the transgene had hypoglycemia and were stunted in growth. Mice with more than 10 copies were markedly stunted in growth and died within 2-4 weeks. Tag expression was detected at high levels in the mouse tumors but not in any other tissues, including the hematopoietic cells.

Animals↗

Proenzyme from of cathepsin L produced by thymic epithelial cells promotes proliferation of immature thymocytes in the presence of IL-1, IL-7, and anti-CD3 antibody.

A thymic epithelial cell line (TEC1-4) established from newborn mouse thymus produced a cofactor to promote proliferation of double-negative (CD4-8-) thymocytes in the presence of IL-1, IL-7, and anti-CD3 antibody. Based upon the sequence of 8 amino acid residues near the N terminal portion, the factor was identified as the mouse proenzyme form of cathepsin L which is almost identical to the rat proenzyme form of cathepsin L (95% in homology). Production of the proenzyme form of cathepsin L was confirmed in the TEC1-4 and mouse embryonic thymus by Western blotting analysis and Northern blotting analysis. Furthermore, immunohistologically, the presence of cathepsin L was observed in the epithelial cells of the subcapsular layer and around the small vessels in the thymic cortex. It has been concluded that a subpopulation of thymic cortical epithelial cells produces the proenzyme form of cathepsin L which can act as a cofactor to promote proliferation of DN immature thymocytes.

Amino Acid Sequence↗

The intrapleural administration of recombinant interleukin-2 (rIL-2) to patients with malignant pleural effusion: clinical trials.

Recombinant IL-2 (rIL-2) was administered intrapleurally according to an original protocol to 11 patients with malignant pleural effusion, 7 of whom suffered from breast cancer and 4 from esophageal cancer. The pleural effusions either disappeared or decreased roentgenographically, and malignant cells disappeared from all 13 pleural cavities in the 11 patients, confirming the validity of this therapy to be 100%. The mean survival time from the initial administration of rIL-2 was 15.9 months. We ensured that the concentration of IL-2 in the effusion was maintained at a high level for a sufficient period of time, and that the lymphokine-activated killer (LAK) activity of lymphocytes in the effusion was augmented. Fever, eosinophilia, and a transient increase in the pleural effusion were the main side effects, but the symptoms were temporary and not serious. The results of this study therefore suggest the efficacy of intrapleural rIL-2 for patients with malignant pleural effusion.

Adult↗

Renal fibroblasts are sensitive to growth-repressing and matrix-reducing factors from activated lymphocytes.

Various forms of nephropathy accompany interstitial fibrosis with lymphocytic infiltration. To probe the relationship between lymphocyte-derived factors and renal fibroblasts, we studied the effect of culture supernatant from lymphocytes stimulated by concanavalin A (ConASN) on the growth and matrix metabolism of rat kidney fibroblasts. 3H-thymidine incorporation and Northern analysis, respectively, revealed that ConASN repressed cell growth and the mRNA level of collagen type I, but dramatically elevated the steady-state expression of metalloproteinase transin/stromelysin. The growth inhibitor in ConASN was moderately heat-sensitive and less than 5 kD in molecular size, qualities that differed from those of transforming growth factor-beta (TGF-beta), IL-1 beta, IL-6, and tumour necrosis factor-alpha (TNF-alpha). The matrix regulatory factor in ConASN was highly heat-sensitive and more than 30 kD in size. Among several lymphokines tested, TNF-alpha produced the same effects as ConASN on the metabolism of extracellular matrix. We hypothesize that lymphocyte-derived factors have a significant role in the attenuation of renal fibrogenesis, as well as its progression, via inhibiting cell growth and matrix accumulation.

Animals↗

Mechanical circulatory support for postcardiotomy ventricular failure: the Heart Institute of Japan experience 1984-1992.

In the last 9 years, 30 patients received assisted circulation or a ventricular assist device after open-heart operations at the Heart Institute of Japan. After cardiovascular surgery, 9 of those patients underwent venoarterial bypass, 10 had biventricular bypass, 7 had left ventricular bypass, and the remaining 4 received a left ventricular assist device. Of the first 15 patients, only 3 (20%) were discharged from the hospital. In contrast, 7 (46.7%) of the last 15 patients were discharged without major complications. With respect to complications, bleeding and ventricular arrhythmia (immature weaning) decreased with low-heparinized isolated left ventricular supports. However, profound biventricular failure, infection, and multiple organ failure remain as possible complications with any type of assisted circulation. These results suggest that early application of circulatory support and appropriate selection of the mode of support and devices used are important for successful circulatory support.

Adult↗

Percutaneous cardiopulmonary support as the second generation of venoarterial bypass: current status and future direction.

We have developed a new percutaneous cardiopulmonary support (PCPS) system in cooperation with Terumo Corporation, called the Emergency Bypass System (EBS). This preassembled system is unique in terms of its small priming volume (470 cc), fully automatic priming function, originally developed membrane oxygenator, and Capiox straight path centrifugal pump. The priming process takes only 5 min. We have used this system in 4 patients (all were male; mean age 56 years, range 35-73 years). The duration of assist ranged from 15 min to 210 h. Maximum bypass flow ranged from 2.2 to 3.6 L/min, systemic circulation was very well maintained, and urinary output was acceptable. Although the centrifugal pump was in good working condition, we had to change the oxygenator because of serum leakage 36 to 48 h after initiation of the assist. One patient was weaned from the PCPS, but died of brain death. The other patients could not be weaned from the PCPS. The cause of death in these patients was irreversible myocardial damage. Disseminated intravascular coagulopathy triggered by surgical trauma related to various procedures developed in 2 patients during assist and was the cause of cessation of the assist. Problems to be ratified and future directions in the EBS and PCPS were earlier introduction through the establishment of clear indications and endpoint, heparin coating, improvement in durability of the oxygenator, and cost.

Adult↗

Development of fabrication system of prostheses using electric discharge machining.

This paper outlines the principles and uses of electric discharge machining (EDM) in the fabrication of prostheses. The three areas of use of EDM are classified as supplementary use, direct fabrication of crowns and bridges and fabrication of titanium copings using a CAD/CAM process. The problems associated with the use of EDM in each area are discussed and the methods employed to overcome these problems are described. The application of numerically controlled (NC) EDM to prosthodontic work is found to be promising. Further refinement and development are necessary before EDM can be widely accepted as a means of fabricating prostheses.

Computer-Aided Design↗

[Congenital arteriovenous malformation of the kidney: report of two cases--detection by digital subtraction angiography with carbon dioxide].

Two cases of arteriovenous malformation of the kidney were reported. The first case was a 19-year-old female, complaining of right flank pain and gross hematuria. Right selective renal arteriography revealed a 2 x 1.5 cm large cisoid type arteriovenous malformation at the most distal region of the lower branch of the renal artery. Transcatheter embolization, using Gelfoam and absolute ethanol, was successfully done, which was confirmed with repeated digital subtraction angiography with carbon dioxide (CO2-DSA). The second patient was a 55-year-old female with past history of right idiopathic renal bleeding, complaining of right flank colicky pain and gross hematuria. Right selective renal arteriography was done without any pathological findings, while CO2-DSA documented an arteriovenous malformation in the hilar region. Transcatheter embolization was not done, because the malformation seemed to be proximally located. Thus CO2-DSA was thought to be a reliable method in the diagnosis of arteriovenous fistula.

Adult↗

Photochemical cleavage of DNA by phosphorus(V) porphyrin derivatives.

Photocleavages of double-stranded circular DNA and oligonucleotide were investigated by the use of phosphorus(V)tetraphenylporphyrin (P(V)TPP) derivatives. The P(V)TPP derivatives cleaved the DNA and the oligonucleotide under the visible light irradiation, in air and in argon, respectively. It is suggested that the photocleavage reactions include an electron transfer mechanism as well as a singlet oxygen (1O2) one.

Bacteriophage phi X 174↗

[The effectiveness of ulinastatin on granulocyte H2O2 production in acute lung injury rat model].

Oxygen radicals produced by granulocytes play an important role in acute lung injury. The effectiveness of ulinastatin in adult respiratory distress syndrome and an acute lung injury animal model has been reported. We investigated the effect of ulinastatin on oxygen radical production in the intact pulmonary circulation of a rat acute lung injury model using our new method, which demonstrated the granulocyte adhesion and H2O2 production in vivo. The pulmonary microcirculation was observed by intravital fluorescence microscopy and a TV monitor using a SIT TV camera. Then images were recorded on a videotape. The granulocytes and H2O2 were stained with an intravenous injection of acridine red and dichlorofluorescin diacetate, respectively. The images which were recorded on the videotape were digitized by a computer image digitizer and analyzed with a personal computer and the software Ripp II. When the rat received a continuous infusion of endotoxin (4.5 mg/kg/hour) for 2 hours, the granulocytes adhered to the pulmonary capillaries and generated H2O2 (n = 25 p < 0.001 respectively, compared with the control rat which received saline alone). Then, the acute lung injury model rat was infused with 50,000 U/kg of ulinastatin just before endotoxin infusion and also received a continuous infusion of ulinastatin (50,000 U/kg/hour) for 2 hours. Ulinastatin inhibited the granulocyte adhesion to the pulmonary capillaries (n = 25, inhibition rate: 46% p < 0.001) and H2O2 production (n = 25, inhibition rate; 51% p < 0.001) caused by the continuous infusion of endotoxin. In conclusion, ulinastatin significantly inhibits the granulocyte adhesion and H2O2 production in the intact pulmonary circulation of a rat acute lung injury model.

Acute Disease↗

[Quantitative analysis of right ventricular overloading by 201Tl myocardial SPECT].

Clinical usefulness of quantitative analysis of right ventricular overloading was evaluated by 201Tl myocardial SPECT in comparison with cardiac catheterization and MRI. Seventy-four MBq of 201TlCl was intravenous injected and 201Tl myocardial SPECT was performed on 40 patients (mean age: 61.0 +/- 11.8) with right ventricular overloading. Regions of interest (ROI) were selected on right and left ventricular walls in a midventricular short axis image of SPECT and uptake of each ROI were counted. The right ventricle (RV)/left ventricle (LV) 201Tl uptake ratio (R/L-Tl) was calculated. Wall thickness of RV and LV were measured on MRI and the RV/LV wall thickness ratio (R/L-WT) was calculated. RV and LV pressure were recorded in cardiac catheterization, and the RV/LV systolic pressure ratio (R/L-P) was calculated. There was significant positive correlation (Y = 0.73X + 0.19, r = 0.71, p < 0.001) between R/L-Tl and R/L-WT. R/L-Tl was positively correlated with R/L-P in patients with pressure overload (Y = 1.14X - 0.049, r = 0.85, p < 0.001) and in patients with volume overload (Y = 0.51X + 0.023, r = 0.88, p < 0.001) and the slope of the regression line in patients with pressure overload was significantly steeper than that in patients with volume overload (p < 0.001). In conclusion, quantitative analysis of right ventricular overload by 201Tl myocardial SPECT is useful to estimate RV/LV wall thickness ratio and pressure ratio.

Adult↗

[Mechanical circulatory support for profound heart failure].

Profound heart failure, such as acute myocardial infarction with cardiogenic shock and postcardiotomy ventricular failure, requires mechanical circulatory support when recent medical treatment is ineffective. Intra-aortic balloon pumping, venoarterial bypass, cardiopulmonary bypass, left ventricular bypass, biventricular bypass and left ventricular assist device are commonly used circulatory support methods. Type selection and application timing of circulatory supports, based on the understanding of type of cardiac failure, respiratory function and other organ conditions, appears to be most important for successful treatment of profound heart failure.

Assisted Circulation↗

[A resected case of well-differentiated adenocarcinoma simulating fetal lung tubules which is a variant of pulmonary blastoma].

A case of well-differentiated adenocarcinoma simulating fetal lung tubules which is a variant of pulmonary blastoma is reported. A 31-year-old female with an abnormal shadow in the right upper lung field detected by chest X-P during a follow-up for sarcoidosis during pregnancy underwent right upper lobectomy. Post operative histological diagnosis was well-differentiated adenocarcinoma simulating fetal lung tubules. This tumor might be a variant of pulmonary blastoma lacking the sarcomatous features and showing one-sided development of the epithelial component. However, it has been reported by various names, and classifications of pulmonary blastoma differed slightly depending on the reporter. There are also some discrepancies in the clinical course and prognosis of the tumor. Therefore it is considered that further examination of this tumor is necessary.

Adenocarcinoma↗

[Pathological assessments of allografts after heart transplantation using a dog model--allograft vasculopathy].

The pathological findings of allografts after heart transplantation were assessed in long-term period using a dog model. Eight orthotopic heart transplantations were performed with cross-circulation method using a dog. Two dogs survived over 1 year after heart transplantation. One dog died due to cardiac rejection, and the another dog died due to infection at 14 months and 16 months after the transplantation, respectively. The coronary artery morphologic features were assessed in the allografts. The pathological findings showed fibrous intimal thickening with infiltration of lymphocytes and macrophages. And it was diffusely distributed to each area of transplanted heart. The stenosis of coronary lumen was significantly seen in middle size of coronary arteries which was from 100 microns to 50 microns. The characteristics of these findings in comparison with arteriosclerosis change were 1) rapid progression, 2) diffuse fibrous intimal thickening, 3) preserved internal elastic lamia. These findings might be important for treating this complication.

Animals↗

[Effectiveness of continuous retrograde cerebral perfusion for surgical treatment of aneurysms of the aortic arch--comparison with antegrade cerebral perfusion].

Several methods have been used for an adjunct to perform operation of aortic arch aneurysms. However, their results were often not so reasonable. Recently retrograde cerebral perfusion was reported as a new adjunctive method. In our institute, for the past 6 and a half years from May 1985 to April 1992, 50 patients underwent reconstruction of the transverse aortic arch by using two methods of artificial cerebral perfusion. One method is continuous antegrade cerebral perfusion (ACP, for 32 patients), and the other is continuous retrograde cerebral perfusion (RCP, for 18 patients), each technique was combined with deep hypothermia (18-20 degrees C) and low flow perfusion (10-30 ml/kg/min) to lower half body performed from femoral artery. In our RCP circuit, an additional pump was used for cerebral perfusion to superior vena cava, but the circuit was much simpler than the circuit in ACP. We compared the two methods (ACP versus RCP) as regards to the following items and the results were showed in parentheses; hospital death (8/32, 25%: 2/18, 11%), respiratory complication (8.27, 30%: 3/18, 17%), neurological complication (7/29, 24%: 1/18, 5.5%), duration of extracorporeal circulation (306.8 +/- 74.5 min: 260.4 +/- 60.0 min), periods of pre-ECC in the operation (160.3 +/- 69.2 min: 117.7 +/- 35.3 min), duration of cerebral perfusion (113.6 +/- 45.4 min: 74.1 30.5 min) and amount of bleeding (3424 +/- 2881 ml: 1802 +/- 1291 ml). RCP has superior advantages in all of those in comparison with ACP. These results suggest that RCP is a useful adjunctive method for reconstruction of aortic arch with a low operative risk.

Adult↗

[Sutureless aortic valve replacement for peri-annular pseudoaneurysm and perivalvular leakage due to prosthetic valve endocarditis].

A 49-year-old man who had undergone AVR entered our hospital with congestive heart failure and continuing slight fever. By cardiac imaging, he was diagnosed prosthetic valve endocarditis with periannular pseudoaneurysm and perivalvular leakage. He underwent a new translocation method using a composite valve (a prosthetic valve directly sutured a ring prosthesis, which was separated from an intraluminal ringed graft). Post operative course was uneventful. He recovered well after the operation.

Aneurysm, False↗

[Intraperitoneal repeated chemotherapy using CDDP combined with MMC for carcinomatous peritonitis].

Based on our experimental study, which indicated that simultaneous combined administration of MMC and CDDP prolonged life more significantly than individual administration, clinical application was performed on three cases of carcinomatous peritonitis from Borrmann type 4 cancer of the stomach. The dosage was 14 mg/m2 (7 mg/m2 at second and following administrations) of MMC and 35 mg/m2 of CDDP and they were repeatedly administered in the abdominal cavity via the drug delivery system. As the result, no severe toxicities were found except for two cases of leukopenia (Grade 2). Effectiveness was indicated in all cases with the negative change of cytology, whereas no improvements in prognosis were obtained. We concluded that some new devices would be necessary to increase the drug delivery to the carcinomatous wall.

Adenocarcinoma↗