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Biomedical subjects

H Imamura

Publications and source records attributed to H Imamura.

At least 19 recordsLinked to original sources

Cold ischemia-reperfusion injury of the liver. Role of the liver donor nutritional status in rats.

To verify the role of donor nutritional status on the quality of liver preservation after cold storage, we assessed hepatocyte and liver endothelial cell viabilities and functions in an isolated perfused rat liver model. Livers from fed and fasted Wistar rats were isolated and perfused either immediately after liver harvesting or after a 24-hr cold (4 degrees C) preservation in University of Wisconsin solution. Hyaluronic acid (150 ng/ml) and taurocholate (11.5 micrograms/ml) were infused into the reservoir, and their eliminations were assessed to evaluate liver endothelial cell function and hepatocyte function, respectively. Liver viability was estimated by intrahepatic resistance, oxygen consumption, bile secretion, and lactate dehydrogenase release. In addition, cell viabilities were evaluated by trypan blue staining. In fed-rat livers, glycogen content did not differ before or after the cold preservation, although a reduction was observed during the subsequent perfusion period. Liver glycogen content in fed rats was markedly higher than in the fasted rats at each time point studied. In fasted and fed rats, liver viability parameters and hepatocyte function were moderately altered, whereas liver endothelial cell function was markedly impaired after cold preservation. However, feeding had no influence on either hepatocyte or liver endothelial cell functions which were similarly altered in both nutritional conditions. The present data show that the nutritional status of liver donors does not play an important role in the preservation of liver endothelial cells after cold ischemia-reperfusion and, thus, should not affect the overall resistance of livers to hypothermic-ischemic injury.

Adenosine

Histopathological study of local residual carcinoma after simulated lumpectomy.

From 1989 to 1991, 24 patients with invasive ductal carcinoma underwent simulated lumpectomy at Tokyo Women's Medical College Daini Hospital. The mastectomy specimens were then examined histopathologically in serial sections for the presence of residual tumors or multicentricity. Lumpectomy specimens from cancer foci at resected margins were also examined. In this study, 23 of 24 patients demonstrated positive resection margins (95.8%). Residual tumors were found in mastectomy specimens from 16 patients (66.7%); unilateral multifocal carcinomas were found in 2 of these patients (8.3%). The incidence and severity of residual tumors did not correlate with primary tumor size or the distance between the nipple and the primary tumor but directly correlated with the severity of intraductal spread of the primary tumor. Tumors with central necrosis were associated with a higher incidence of residual tumors. Our study thus indicates that there is a high risk that some residual tumor will be left in the conserved breast when lumpectomy is performed. Multifocal carcinoma and tumors showing severe intraductal spread and central necrosis are thus associated with extensive residual tumors and are likely to cause local recurrence.

Breast Neoplasms

Relationship between staining by digital subtraction angiography and vascularity in breast cancer: analysis of the time-density curve and the results of staining for factor VIII-related antigen/von Willebrand factor.

We performed intravenous digital subtraction angiography (IV-DSA) in 31 patients with primary invasive breast cancer, and calculated the maximum density of tumor staining from the time-density curve obtained. Specimens resected from the same patients were stained for factor VIII-related antigen/von Willebrand factor (vWF), and the amount of microvessels was calculated by image processing. A significant correlation (correlation coefficient: 0.85) was found between the maximum density of tumor staining and the vascularity determined by staining for vWF, indicating that the maximum density indirectly reflects the vascularity in the tumor.

Angiography, Digital Subtraction

Role of Kupffer cells in cold ischemia/reperfusion injury of rat liver.

BACKGROUND & AIMS: Kupffer cell activation is hypothesized to play an etiopathogenic role in storage-related graft failure after liver transplantation. The aim of this study was to verify whether the elimination of Kupffer cells modifies the magnitude of cold ischemia/reperfusion injury of the liver. METHODS: Rat Kupffer cells were eliminated by an intravenous injection of liposome-encapsulated dichloromethylene diphosphonate. Livers from control and treated rats were isolated and perfused before and after 24-hour cold ischemia in the University of Wisconsin solution (4 degrees C). Hepatocyte and sinusoidal endothelial cell functions were evaluated by taurocholate and hyaluronic acid elimination, respectively. Liver transplantation was also performed using control and treated donor livers stored under identical conditions. RESULTS: Compared with baseline values, similar alterations were found in both groups after cold ischemia for hepatocyte function (intrahepatic resistance, bile secretion, lactate dehydrogenase release, oxygen consumption, and taurocholate intrinsic clearance) and for sinusoidal endothelial cell function (hyaluronic acid intrinsic clearance). The 10-day survival rate of animals undergoing transplantation was not different between the groups (6 of 15 vs. 4 of 15, control vs. treated donor livers, respectively). CONCLUSIONS: The presence or absence of Kupffer cells does not modify the effect of 24-hour cold ischemia/reperfusion on the rat liver.

Adenosine

Role of sodium pump activity in warm induction of cardioplegia combined with reperfusion of oxygenated cardioplegic solution.

Na+/K+ adenosinetriphosphatase (sodium pump) may play a key role in the prevention of reperfusion injury caused by Ca2+ overload. The present study was undertaken to investigate the role of sodium pump activity in warm induction of cardioplegia combined with reperfusion of oxygenated cardioplegic solution. Isolated and perfused rat hearts were subjected to 15 minutes of normothermic ischemia to produce a model of severely failing heart. The hearts then received myocardial preservation. Warm (37 degrees C) or cold (4 degrees C) oxygenated modified St. Thomas' Hospital solution was given for 5 minutes before and after 120 minutes of hypothermic cardioplegic arrest. Reduced myocardial pH during normothermic ischemia was adjusted toward the baseline level by administration of cold or warm oxygenated cardioplegic solution without a significant intergroup difference. Myocardial adenosine triphosphate levels decreased to less than 30% of the preischemic level during 15 minutes of normothermic ischemia, but were increased partly by induction of cold or warm oxygenated cardioplegia. Thus these metabolic indices failed to demonstrate the superiority of warm over cold oxygenated cardioplegia. Na+/K+ adenosinetriphosphatase activity in the membrane fraction was significantly stimulated by a cardioplegic dose of K+ with maximum activity at 16 mEq/L. The enzyme activity of the heart measured after normothermic ischemia was reduced to less than 50% of that in the nonischemic heart. Although warm induction of cardioplegia and reperfusion of oxygenated cardioplegic solution maintained Na+/K+ adenosinetriphosphatase activity at the preischemic level, the enzyme activity was abolished at 4 degrees C, which is the temperature used in cold cardioplegia. A subtoxic dose of ouabain (0.1 mmol/L) inhibited the enzyme activity of the heart undergoing this preservation regimen to approximately 50%. Warm induction and reperfusion of oxygenated cardioplegic solution showed significantly better recovery of isovolumic left ventricular function during reperfusion compared with that obtained with cold oxygenated cardioplegia. However, the beneficial effect of warm oxygenated cardioplegia on left ventricular function was compromised by inclusion of 0.1 mmol/L ouabain without a significant effect on myocardial metabolic parameters. These results suggest that stimulation of Na+ pump activity may account for the beneficial effect of warm induction and reperfusion of oxygenated cardioplegic solution in the energy-depleted heart.

Acid-Base Equilibrium

Cytotoxic effects of irradiation and deoxyguanosine on fetal thymus.

Effects of irradiation and deoxyguanosine on the fetal thymus were examined both in vitro and in vivo. Fetal thymi (gestation day 15) of C57BL/6 mice that had been irradiated (0-25 Gy) or treated with various doses of deoxyguanosine (dGuo) were engrafted under the renal capsules of BALB/c nu/nu mice, and the differentiation of T cells was investigated in the engrafted thymi or spleens of these mice. After in vitro treatment of fetal thymi with 1.35 mM dGuo (which was previously reported to be an optimal dose), T cell precursors still remained in some cultures, whereas 1.80 mM dGuo was highly cytotoxic not only to T cell precursors but also to thymic epithelial cells. In contrast, 25 Gy irradiation totally eliminated the T cell precursors from the fetal thymi, though the capacity of epithelial cells to induce T cell differentiation was retained. Although irradiated thymi had the capacity to induce T cell differentiation when assayed in an in vitro organ culture system, long-term observation of thymi engrafted into BALB/c nu/nu mice revealed that, if they had been irradiated (9.5 Gy or 25 Gy), the thymi became scarred by 12 wks after their transplantation. Furthermore, the expression of cell interaction molecules such as ICAM-1 and MHC class II on the thymus stromal cells decreased after irradiation. The interaction molecules decreased 3 wks after 25 Gy irradiation and 7 wks after 9.5 Gy irradiation. The alteration in T cell subsets in the thymus (decreases in both double- and single- positive cells and an increase in double-negative cells) correlated with the decreases in the interaction molecules. This indicates that irradiation (even 9.5 Gy) impairs the T cell-induction capacity of the thymus stromal cells, resulting in an alteration of the T cell subsets followed by a change in the T cell counts in the thymus. Therefore, the long-term effects of irradiation of the thymus should be considered in cases of fetal thymus grafts or total body irradiation before bone marrow transplantation, particularly in the newborn.

Animals

The failure of retrograde continuous warm-blood cardioplegia to resuscitate cardiac function in experimental acute coronary artery occlusion and reperfusion.

The effects of retrograde continuous warm-blood cardioplegia (RCWBC) on myocardial preservation during surgical revascularization for acute coronary artery occlusion were investigated using an isolated in-situ dog heart model. The left anterior descending artery (LAD) was occluded for 60 minutes followed by 60 minutes of cardioplegic arrest and reperfusion after release of the coronary artery occlusion. Thirty one animals were divided into 3 groups according to the manner of cardioplegic arrest. The first group of animals (n=10) received multiple doses of cold St. Thomas' Hospital solution delivered antegradely through the aortic root. The second group of animals (n=11) received the same dose of the crystalloid solution delivered retrogradely through the coronary sinus. The third group of animals (n=10) received RCWBC through the coronary sinus. In the animals which were capable of supporting the working mode after reperfusion (8 hearts in each group), regional myocardial function in the occluded LAD distribution measured by sonomicrometer as well as global myocardial function evaluated by left-ventricular stroke-work index were not significantly improved during reperfusion by RCWBC. Corresponding to the functional data, myocardial pH in the occluded LAD distribution was not significantly increased by RCWBC. Although RCWBC maintained myocardial pH in the circumflex artery distribution at a significantly higher level than the other two groups of hearts undergoing cold crystalloid cardioplegia, RCWBC resulted in a substantial decline of myocardial pH in the right-ventricular free wall. These results suggest that RCWBC after 60 minutes of LAD occlusion may not provide a significant benefit in myocardial preservation compared to cold crystalloid cardioplegia delivered through either an antegrade or retrograde manner.

Animals

Intraoperative spinal sonography in the cervical anterior approach.

Intraoperative spinal sonography was used during cervical anterior approach procedures for cervical discectomy and osteophytectomy to demonstrate spinal pulsation, the protruded disc or osteophyte, the anterior subarachnoid space, and the spinal cord. Spinal pulsation was recognized in some cases before removal of the disc but the anterior subarachnoid space and spinal cord could not be observed. However, the latter were more clearly observed during removal of the disc and could be seen after total removal of the disc and osteophyte. This method allows confirmation of decompression and pulsation of the spinal cord without cutting and removal of the posterior longitudinal ligament.

Adult

[Combined lung resection for advanced thoracic esophageal carcinoma].

We performed lung resection together with esophagectomy in 2 patients with advanced thoracic esophageal cancer. Both patients survived more than 2 years with no evidence of disease. The first case was a 60-year-old man who had a cancer lesion in middle of the intra-thoracic esophagus (Im) and the right lower lobe of the lung was involved. In March 1989, right lower lobectomy of the lung was performed with esophagectomy. Pathologic examination showed well differentiated squamous cell carcinoma invading the lung parenchyma and intrapulmonary lymph node. Postoperatively, 44 Gy of radiation and Peplomycin cancer chemotherapy was performed. The patient survived 51 months after surgery and died of chronic myelogenous leukemia. The second case was a 60-year-old man who underwent thoracic esophagectomy with resection of the involved pericardium and right lung in February 1992. Pathologic examination showed N3 lymph node metastasis. Postoperatively, the patient received 48 Gy of radiation and was free from cancer after 30 months. In conclusion, better surgical results are expected in cases of advanced thoracic esophageal cancer with lung involvement which can be completely resected en bloc with the primary tumor even in a3 cases than in those with aortic or tracheobronchial involvement.

Aged

[Molecular biological mechanism of cancer metastasis and the prediction of metastasis in clinical cases].

An outline of the mechanism of cancer metastasis is presented from a molecular biological point of view, and the present state and future possibility of prediction about cancer metastasis in clinical cases is described. Cancer metastasis is developed through multiple steps. With the progress of studies on the mechanism of metastasis, the effort to predict cancer metastasis in clinical cases has progressed. Metastasis is formed in concern with many factors, so it may be highly difficult to explain clinical metastasis by a single factor. It will be important to comprehensively put many factors into consideration. For the preoperative diagnosis of the potential of metastasis, examination of specimens from endoscopic biopsy or blood serum will become more important.

Cell Adhesion Molecules

[Pneumothorax with reduced pulmonary function complicated by MRSA pneumonia: a case report].

The occurrence of pneumothorax in patients with compromised lung function or severe pulmonary disease may be fatal. We describe a 77-year-old patient with MRSA pneumonia complicated by pneumothorax and reduced pulmonary function. Although the patient was treated with drainage of the pleural cavity and nonsurgical pleurodesis, the pneumothorax could not be managed successfully. The patient underwent successful surgical treatment of the pneumothorax on 105 days after onset. The following factors must be considered in the surgical treatment of pneumothrax with reduced pulmonary function in patients with MRSA pneumonia: 1) When there is massive air leakage, adequate doses of VCM should be administered to prevent pyothorax, 2) when conservative treatment fails and surgical treatment becomes necessary, the operation should be instituted only when MRSA has been completely or almost completely eradicated so as to prevent the occurrence of postsurgical pyothorax, and 3) surgical intervention should be limited to what is necessary to repair the site of ruptured bulla; care should be exercised to preserve as much lung parenchyma as possible and to shorten the operation time.

Aged

[Cisplatin, 5-fluorouracil and leucovorin combination chemotherapy-added radiation therapy for advanced esophageal cancer--a case report].

Cisplatin, 5-fluorouracil and leucovorin combination chemotherapy added radiation therapy was performed for the treatment of 62-year-old male patient with advanced esophageal cancer who had liver cirrlosis. After the treatment, esophageal lesion disappeared. Only minimal side effect occurred during the treatment. Biochemical modulation chemotherapy combined with radiation therapy is useful for advanced esophageal cancer.

Antineoplastic Combined Chemotherapy Protocols

[A case of primary mediastinal teratocarcinoma in a young girl].

Primary malignant germ cell tumors of the mediastinum are rare neoplasm, almost always occurring in young adult males. This report described embryonal carcinoma in a 13-year-old girl. The patient was checked up at chest X-ray examination of middle-school pupils on June 1989, and was referred to us because of rapid enlargement of the shadow on October 1989. Chest rentogenograms on admission showed a large mass at the anterior mediastinum, and MRI also revealed a multicystic one extending to the right hemithorax and pressing the superior vena cava and the right atrium. Her serum AFP level was high at 211.1 ng/ml. At operation, on November 6, 1989, a large tumor (110 x 95 x 75 mm) was removed completely through median sternotomy. Histological study of the lesion revealed a wide spread of cystic mature teratoma containing some foci of embryonal carcinoma. Positive immunochemical reaction indicated the presence of AFP in these carcinoma cells. She was treated with 13 courses of anti-cancer chemotherapy by various combinations of CDDP, THP-ADR, VP-16, VCR, ACD, CPM, CBDCA, for one postoperative year. She showed clinical improvement and has continued to be free from recurrence now at 52 months after surgery.

Adolescent

[A case of metachronous primary cancer of the lung, rectum and trachea].

We reported a metachronous primary triple cancer of lung, rectum and trachea. Patient was a 64-year-old male, who was admitted with a episode of bloody sputum. A chest X-ray and rentogen tomogram showed a irregularity and narrowing of the upper trachea. Transbronchoscopic biopsy specimen showed squamous cell carcinoma. December '92, trachea was resected in the length of five cartilages and end-to-end anastomosis was performed. Microscopic examination demonstrated a moderately differentiated squamous cell carcinoma with mediastinal lymph node metastasis. Therefore, he received a course of 30 Gy of radiation to the upper mediastinum after surgery. Three years before the tracheal resection, he had undergone left pneumonectomy for moderately differentiated squamous cell carcinoma of the lung. Nineteen months after the pulmonary resection, he had undergone low anterior resection of the colon for the rectum carcinoma.

Adenocarcinoma

A modified invasion-3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide assay for quantitating tumor cell invasion.

Reconstituted basement membrane matrix (Matrigel) has been utilized for in vitro assay of tumor cell invasion in recent years. In the conventional chamber for the invasion assay, however, a large number of cells passed easily through the center of the Matrigel-coated filter because the Matrigel layer could not be completely uniform by the meniscus formation. To prevent the meniscus phenomenon of the Matrigel layer, we devised a water-repellent treatment of the inside wall of the assay chamber with paraffin. Consequently, very few erythrocytes passed through the Matrigel-coated filter of this modified chamber with the erythrocyte assay, which was used to demonstrate the evenness and uniformity of the Matrigel layer on the filter. For quantitating a small number of cells which invaded through the Matrigel-coated filter by the invasion assay, a tetrazolium-based colorimetric 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide) assay was used. The invasive abilities of the eight different cells were determined by this invasion-3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium+ ++ bromide assay using the modified chamber with a filter coated with 70 microliters of the 0.2-mg/ml Matrigel. After 72 h of incubation, the malignant cell lines significantly exceeded the normal cell lines in the percentage of invasion (P < 0.01). Therefore, the modified invasion-3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium+ ++ bromide assay provides a simple, easily reproducible in vitro assay for quantitating tumor cell invasion.

Animals

Morphometry of sinusoids and portal hypertension in non-alcoholic cirrhosis.

To examine whether structural changes in hepatocytes and/or sinusoidal areas contribute to the portal hypertensive state in non-alcoholic cirrhosis, a new method of morphometric analysis using a computer-aided color image analyzer was performed in 16 patients with non-alcoholic cirrhosis, which allowed quantitative evaluation of various morphometric parameters of sinusoids and hepatocytes. The sinusoidal pressure gradient was estimated theoretically with these and clearance parameters using Poiseulle's equation and compared with the hepatic venous pressure gradient measure by hepatic vein cannulation. A significant relationship was found between the hepatic venous pressure gradient and sinusoidal volumetric ratio (r = -0.598, p < 0.05), but not between mean hepatocyte volume and sinusoidal volumetric ratio (r = 0.416, NS), or the hepatic venous pressure gradient (r = 0.371, NS). The estimated sinusoidal pressure gradient showed a significant relationship with the hepatic venous pressure gradient (r = 0.637, p < 0.01). However, the absolute values of the former were much lower than those of the latter. Therefore, in non-alcoholic cirrhosis, although sinusoidal stenosis not caused by hepatocyte swelling may lead to increased vascular resistance, other factors must also play a significant role.

Aged

A simple and rapid fluorometric determination method of alpha 1-acid glycoprotein in serum using quinaldine red.

We examined different fluorescent probes suitable for fluorometric determination of alpha 1-acid glycoprotein (AGP) in serum. Quinaldine red (QR) was shown to bind strongly and selectively to AGP. Taking advantage of the enhanced fluorescence of QR in the presence of AGP, we developed a direct method for the determination of serum AGP without removal of other serum proteins such as albumin. AGP concentrations in serum of healthy volunteers and patients correlated well with results from the conventional single radial immunodiffusion (SRID) method (r = 0.93, slope = 1). The newly developed method is faster and has a larger analytical concentration range than the SRID method. This method can also be used to determine AGP in serum of experimental animals, and it can serve to monitor AGP serum concentrations for pharmacokinetic evaluation of basic drugs.

Adult