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M Nakahama

Publications and source records attributed to M Nakahama.

At least 19 recordsLinked to original sources
PubMed2000

Expression of perlecan proteoglycan in the infarct zone of mouse myocardial infarction.

Perlecan, a basal lamina proteoglycan, has been shown to interact with other extracellular matrix (ECM) components, especially type IV collagen, and is thus involved in ECM formation. Perlecan has also been postulated to promote growth factor-receptor interactions, including the binding of basic fibroblast growth factor (bFGF) to its receptor, and to enhance mitogenesis and angiogenesis. To test our hypothesis that perlecan is increased in the myocardial infarct zone, we examined perlecan expression after experimentally induced myocardial infarction in BALb/c mice by the methods of in situ hybridization, Northern blotting, and immunohistochemistry. In situ hybridization revealed mRNA signals for perlecan in the infarct marginal zone on day 2 and in the infarct interior zone around infarct granulation tissue on day 7. On day 14 the signals were observed at the center point of the infarct. The signals were detected in spindle-shaped mesenchymal cells (fibroblasts and myofibroblasts). Some surviving myocytes in the infarct marginal zone also showed positive signals. The sequential changes in the perlecan mRNA signal distribution paralleled those for type IV collagen mRNA. Northern blotting demonstrated increased expression of perlecan consistent with the observations of in situ hybridization. Immunopositive staining for perlecan was observed in the infarct zone around granulation tissue on day 7 and in the entire infarct zone on days 14-28. Immunostaining for bFGF was localized surrounding the infarct granulation tissue on day 7 and overlapped with perlecan immunostaining. The present results demonstrated the expression of perlecan by spindle-shaped mesenchymal cells (fibroblasts and myofibroblasts) and some surviving myocytes in the myocardial infarct, indicating the contribution of perlecan to the pathological course of myocardial infarction.

Animals↗
PubMed2000

Time-dependent changes of decorin in the infarct zone after experimentally induced myocardial infarction in rats: comparison with biglycan.

Decorin, a small dermatan sulphate proteoglycan, has been postulated to interact with other components of the extracellular matrix. We examined time-dependent changes of decorin in the infarct zone after experimentally induced myocardial infarction in rats by Northern blotting, in situ hybridization, and immunohistochemistry. The expression of decorin mRNA was compared to that of biglycan mRNA. Northern blotting demonstrated that the decorin mRNA expression was not increased in the infarct zone on day 2, while increased biglycan mRNA was observed at that time (average 3.1-fold increase). Decorin mRNA expression was increased on day 7, and reached a peak (average 2.2-fold increase) around day 14. Biglycan mRNA expression also reached a peak level around day 14 (average 13.3-fold increase). In situ hybridization revealed that mRNA signals for decorin did not appear in the infarct zone on day 2, while biglycan mRNA signals were observed. Decorin mRNA signals were observed in spindle-shaped mesenchymal cells in the infarct peripheral zone on day 7. The decorin mRNA signals appeared later than those of biglycan. Immunopositive staining for decorin was observed in the infarct zone on day 7. The present results demonstrated a time-dependent increase in decorin mRNA expression in mesenchymal cells in the infarct zone in rats. Decorin mRNA appeared later and was increased to a lower extent in the infarct zone than biglycan mRNA.

Animals↗
PubMed2000

Greater than normal expression of the collagen-binding stress protein heat-shock protein-47 in the infarct zone in rats after experimentally-induced myocardial infarction.

BACKGROUND: The heat-shock protein with relative molecular mass 47,000 (HSP47) can bind to procollagen molecules in the endoplasmic reticulum, and acts as a molecular chaperone during the processing and secretion of procollagen. OBJECTIVE: To test our hypothesis that HSP47 is expressed in the myocardial infarct zone. METHODS: We induced myocardial infarction in male Sprague-Dawley rats by ligation of left coronary artery. The expression of HSP47 was examined by Northern blotting, in-situ hybridization, Western blotting and immunohistochemistry. The time-dependent change in the distribution of HSP47 messenger RNA (mRNA) signal was compared with the changes in expression of alpha 1(I) and alpha 1(III) collagen mRNA by in-situ hybridization. The hypoxic induction of HSP47 in cultured cardiac fibroblasts was examined by Northern-blot analysis. RESULTS: Northern blotting demonstrated that the expression of HSP47 mRNA had increased on day 2, reaching a maximum level around day 14 (induced 3.5-fold compared with the preligation hearts) and was maintained at a high level up to day 28. In-situ hybridization analysis revealed HSP47 mRNA signals in spindle-shaped mesenchymal cells located between surviving myocytes in the infarct's peripheral zone 24 h after the ligation, and in the entire infarct zone on day 14. The sequential changes in distribution of HSP47 mRNA signal were identical to those of the alpha 1(I) and alpha 1(III) collagen mRNA. Western blotting demonstrated that expression of HSP47 protein in the infarct zone had increased. Immunofluorescent staining revealed positivity for HSP47 in the infarct's peripheral zone on day 2 and in the entire infarct zone on day 14. Northern blotting revealed that the expression of HSP47 mRNA in cultured cardiac fibroblasts in hypoxic cultures was greater than that in normoxic cultures. CONCLUSION: The present data demonstrated that an increase in expression of HSP47 is produced by spindle-shaped mesenchymal cells in the infarct zone. Expression of HSP47 mRNA was concurrent with the expression of collagen mRNA of types I and III. Hypoxia is one of the factors which induces expression of HSP47.

Animals↗
PubMed1999

Establishment of a long-surviving murine model of myocardial infarction: qualitative and quantitative conventional microscopic findings during pathological evolution.

Ongoing basic molecular analyses are being performed in mice, and a simple long-surviving murine model of myocardial infarction (MI) would be very useful in this regard. Although a few studies have induced MI in mice by coronary artery ligation, the induction involves a complex technique and has a relatively high mortality rate. In addition, the identification of the basic pathological sequence is essential to the interpretation of experimental results. We developed a simple technique for the induction of MI in mice and examined qualitative and quantitative conventional microscopic findings during the pathological evolution over a 28-day observation period. Male BALB/c mice weighing approximately 25-30 g were anesthetized and then ventilated with a positive pressure ventilator. The heart was exposed by thoracotomy. Left coronary artery occlusion was performed by thermocoagulation using a thermocoagulation knife at the level of the tip of the left atrium. After establishing this surgical method, we used it to induce MI in 71 mice. The operative and postoperative mortality rates of this model were 5.6% (4/71) and 12.6% (9/71), respectively. In 3 (5.2%) of the 58 surviving mice, the area of infarct was not sufficient. The infarct area in the remaining 55 mice was 40 +/- 9% of the entire perimeter of the left ventricle. Conventional microscopic examinations with hematoxylin-eosin and Masson-trichrome staining disclosed that all of the characteristic histopathological features of MI occurred 1-2 days earlier than those in rats. Our surgical technique provides a sufficient infarct area, with an acceptable mortality rate. The present study clarified the histopathological sequence in this long surviving murine MI model.

Animals↗
PubMed1999

Reperfusion accelerates the distribution of type I and III collagen messenger RNA expression after acute myocardial infarction: in situ hybridization in experimental infarction in rats.

BACKGROUND: The effects of reperfusion on the time-dependent appearance and distribution of type I and III collagen messenger RNA (mRNA) expression had not hitherto been examined. OBJECTIVE: To compare the sequential changes in the extent of distribution of type I and III collagen mRNA expression in reperfused infarct hearts of rats with those in unreperfused infarct hearts. METHODS: Using an experimental rat model of infarction, we examined type I and III collagen mRNA expression with specific rat pro alpha 1 (I) and human pro alpha 1 (III) collagen riboprobes by in-situ hybridization. Reperfusion was established after a 2 h coronary ligation that produced complete necrosis of the myocytes. RESULTS: Positive signals both for alpha 1 (I) and for alpha 1 (III) collagen mRNA appeared in the infarct peripheral zone 12 h after coronary ligation both of the reperfused and of unreperfused hearts. The spread of signal into the infarct central zone occurred 1-2 days earlier for the reperfused hearts than it did for the unreperfused hearts. The difference between the distributions of signals for the reperfused and unreperfused hearts became obscure on day 14. No notable difference between the extents of signal distribution for alpha 1 (I) and alpha 1 (III) collagen mRNA was obtained. We observed intense signals from spindle-shaped mesenchymal cells (myofibroblasts and fibroblasts) located between surviving myocytes in the marginal zone of the infarct. No myocyte exhibited signals both for alpha 1 (I) and for alpha 1 (III) collagen mRNA. CONCLUSION: In the present study, using in-situ hybridization, we demonstrated that reperfusion accelerates the distribution of expression both of alpha 1 (I) and of alpha 1 (III) collagen mRNA in the infarct zone after acute myocardial infarction in rats.

Animals↗
PubMed1998

Expression of the alpha 1 and alpha 2 chains of type IV collagen in the infarct zone of rat myocardial infarction.

Healing processes affect ventricular remodeling, an important prognostic factor in acute myocardial infarction (AMI). Type IV collagen, a major component of the basement membrane, has been demonstrated to appear in the infarct zone. Six type IV alpha chains, alpha 1 to alpha 6 [alpha 1(IV) to alpha 6(IV)], have been identified. We examined the expression of the alpha 1(IV), alpha 2(IV), alpha 3(IV) and alpha 5(IV) in experimental rat AMI induced by permanent ligation of the left coronary artery in male Sprague-Dawley rats. Neonatal cardiac fibroblasts cultured to reach confluency were also used to examine the hypoxic induction of the expression of these chains. Northern blotting, in situ hybridization, and immunohistochemical staining were employed to examine the alpha chain expression. With the in situ hybridization, alpha 1(IV) and alpha 2(IV) mRNA signals were observed in spindle-shaped mesenchymal cells in the intercellular spaces, in the vascular endothelial cells and in some myocytes in the normal myocardium. Signals for both alpha 1(IV) and alpha 2(IV) mRNA appeared in the spindle-shaped mesenchymal cells located between the surviving myocytes in the infarct peripheral zone at 24 h after the ligation. These signals extended into the central zone and reached the center point of the infarct 5 days after the ligation. Neither alpha 3(IV) nor alpha 5(IV) mRNA signals were observed in the infarct zone. Northern blotting demonstrated increased expressions of alpha 1(IV) and alpha 2(IV) mRNA in the infarct zone compared to the sham-operated hearts. The expression of alpha 5(IV) mRNA was weak in the sham-operated hearts but was not detected in the infarct zone. alpha 3(IV) mRNA was not expressed in the infarct zones or sham-operated hearts. In the cultured cardiac fibroblasts, a hypoxic induction of the expression of both alpha 1(IV) and alpha 2(IV) mRNA was demonstrated by Northern hybridization. Immunohistochemistry revealed alpha 1(IV) and alpha 2(IV) staining in the infarct lesion. The findings demonstrate that among the type IV collagen alpha chains examined, alpha 1(IV) and alpha 2(IV) produced by mesenchymal cells appeared in the infarct zone, suggesting that type IV collagen composed by alpha 1 and alpha 2 chains contributes to the pathological course of myocardial infarction.

Animals↗
PubMed1998

Increased expression of connective tissue growth factor in the infarct zone of experimentally induced myocardial infarction in rats.

Connective tissue growth factor (CTGF), a 36- to 38-kDa peptide, is selectively induced by transforming growth factor-beta and has been suggested to contribute to tissue repair. To test the hypothesis that CTGF is expressed in myocardial infarct tissue following acute myocardial infarction (AMI), we examined CTGF expression after AMI was experimentally induced in rats. Myocardial infarction was induced by left coronary artery ligation in male Sprague-Dawley rats. Northern blotting demonstrated that the CTGF mRNA expression on days 2, 7 and 14 was increased by 6-, 23- and 8-fold, respectively, compared to that in the pre-ligation hearts. In situ hybridization revealed CTGF mRNA signals on day 2 in myocytes in the infarct marginal zone and spindle-shaped mesenchymal cells (presumably myofibroblasts and fibroblasts) located between surviving myocytes in the infarct peripheral zone. On day 7, the signals were observed in the inner lesion of the infarct around infarct granulation tissue. Western blotting demonstrated that the CTGF protein expression on days 2, 7 and 14 was increased compared to the pre-ligation hearts. Immunopositive staining for CTGF was observed in the inner lesion of the infarct tissue on day 7. In conclusion, the findings demonstrated the increased expression of CTGF in the infarct tissue. Myocytes in the infarct marginal zone and spindle-shaped mesenchymal cells (presumably myofibroblasts and fibroblasts) were the cells responsible for CTGF production.

Animals↗
PubMed1998

Sequential changes in the localization of the type IV collagen alpha chain in the infarct zone: immunohistochemical study of experimental myocardial infarction in the rat.

Collagen, as a component of the extracellular matrix, have a role in the healing process after myocardial infarction (MI). For type IV collagen, a major structural protein present in the basal membrane of myocytes, six alpha chains [alpha 1 (IV)-alpha 6(IV)] have been identified. We examined the sequential changes in the appearance and localization of the alpha 1 (IV)-alpha 5(IV) after experimental MI in rats. Hearts were excised from 1 day to 8 weeks after permanent left coronary artery ligation. Immunohistochemical staining with monoclonal antibodies was performed. On day 3, staining for both alpha 1(IV) and alpha 2(IV) first appeared, forming a wavy pattern in the infarct peripheral zone, and the staining was not restricted to the cell membrane. The staining intensity and distribution for both alpha 1(IV) and alpha 2(IV) in the peripheral zone then gradually increased, reaching a maximum around day 7. The distribution progressed from the peripheral to the central zone of the infarct for 1-2 days, reaching the center point after 2 weeks. The staining distribution gradually decreased after reaching the maximum, but the staining had not completely disappeared at 8 weeks. In contrast, no positive staining for alpha 3(IV), alpha 4(IV) or alpha 5(IV) was observed at any time during the 8-week observation period. Thus, the present results demonstrated that in rats, type IV collagen consisting of alpha 1 and alpha 2 chains appears in the infarct zone at a relatively early phase after MI, indicating that type IV collagen composed of alpha 1 and alpha 2 chains contributes to infarct healing.

Animals↗
PubMed1998

Localization of type IV collagen alpha chain in the myocardium of dilated and hypertrophic cardiomyopathy.

A total of 6 alpha chains [alpha 1 (IV) to alpha 6 (IV)] have been identified in type IV collagen. We examined the localization of these chains in the myocardium of patients with dilated (DCM) and hypertrophic (HCM) cardiomyopathy. The localization of alpha 1 (IV)-alpha 6 (IV) in biopsy specimens of 5 patients with DCM and 4 with HCM was examined using immunohistochemistry with monoclonal antibodies. Both alpha 1 (IV) and alpha 2 (IV) immunostaining formed thin homogeneous outlines around myocytes in control hearts. In the DCM specimens, alpha 1 (IV) and alpha 2 (IV) immunostaining formed thick and irregular patterns around myocytes. Staining for alpha 1(IV) and alpha 2 (IV) was also observed in some enlarged intercellular spaces. In 3 DCM hearts, moderate staining for alpha 1 (IV) and alpha 2 (IV) was observed in small replacement fibrotic lesions. In large replacement fibrotic lesions, no alpha 1 (IV) or alpha 2 (IV) staining was observed. In the HCM specimens, alpha 1 (IV) and alpha 2 (IV) staining formed thick homogeneous patterns around myocytes. In the enlarged intercellular spaces, no alpha 1 (IV) or alpha 2 (IV) staining was observed. No labeling for alpha 3 (IV)-alpha 6 (IV) was observed in any heart examined. In conclusion, the present results demonstrate that type IV collagen consisting of alpha 1 and alpha 2 chains appears in the fibrotic lesions of DCM, indicating its contribution to the development of fibrotic changes in the myocardium of DCM patients. In contrast, type IV collagen was restricted to the myocyte membrane in the HCM hearts. Fibrotic processes in the intercellular spaces may differ between DCM and HCM hearts.

Adult↗
PubMed1998

Double-sector Lorenz plot scattering in an R-R interval analysis of patients with chronic atrial fibrillation: incidence and characteristics of vertices of the double-sector scattering.

Animal experiments have demonstrated that the minimum R-R interval during atrial fibrillation is proportional to the functional refractory period of the atrioventricular node. On Lorenz plots, atrial fibrillation is characterized by sector-shaped scattering; the vertex of the sector (ie, the minimum R-R interval) represents the functional refractory period. According to the atrioventricular nodal dual-pathway theory, it was hypothesized that the dual atrioventricular nodal pathways associated with chronic atrial fibrillation represent two vertices with two sectors. Detection of two-sector Lorenz plot scattering was attempted in 48 patients with chronic atrial fibrillation who underwent 24-hour ambulatory electrocardiography. Lorenz plot scattering was constructed by means of a computer. Two sectors, suggesting dual pathways, were detected in 19 (40%) of the 48 patients. The two vertices, located at 388 +/- 61 ms (mean +/- SD) and 580 +/- 60 ms were considered to represent the functional refractory periods of the fast and slow pathways, respectively. The vertex indicating the fast pathway showed greater circadian variation than that indicating the slow pathway. In one patient with dual-sector Lorenz plot scattering, whose atrial fibrillation spontaneously converted to sinus rhythm, an electrophysiologic study demonstrated dual atrioventricular nodal pathways. Thus, the Lorenz plot analysis identified two sectors, indicating the dual pathways, in approximately 40% of the patients with chronic atrial fibrillation, and the characteristics of the functional refractory periods of both pathways were estimated from the characteristics of the vertices. Although this study did not provide direct evidence of the dual atrioventricular nodal pathways, the analysis of Lorenz plot scattering may be clinically useful for studying the effects of drugs and/or ablation on the ventricular response in patients with atrial fibrillation based on the dual atrioventricular nodal pathway theory.

Aged↗
PubMed1996

Floating gallbladder associated with histologically distinct double cancers.

A case of unusually hypermobile floating gallbladder in a 79-year-old woman with histologically distinct double cancers of the gallbladder is described. The patient presented with an abdominal cystic mass, which was palpable with easy mobility from the right lower quadrant practically to the left upper quadrant. Exploratory laparotomy was performed and the cystic mass was found to be a floating gallbladder. The cystic duct was elongated and obstructed, and had a long mesentery. After the operation, latent double cancers of the gallbladder were discovered on histopathological examination. The obstruction of the cystic duct was due to chronic inflammation and had resulted in hydrops of the gallbladder. This was suspected to have played an important role in the carcinogenesis. We believe that this is the first report of a floating gallbladder associated with double gallbladder cancers.

Adenocarcinoma↗
PubMed1994

[A case of resected gastric cancer in which cancer had apparently disappeared by preoperative administration of tegafur].

This paper reports a case of gastric carcinoma in which cancerous tissue was not found in the resected specimen, apparently due to preoperative tegafur administration. The patient was a 56-year-old woman who was diagnosed by initial endoscopic examination including endoscopic biopsy as having an advanced gastric cancer of Borrmann type 2. During the waiting period for operation, she was placed on oral administration of tegafur (Futrafur capsule) 600 mg 3 times a day for 31 days. The second endoscopic examination 14 days later showed reduction of both marginal elevation and central excavation of the lesion, and biopsy at this time was negative for carcinoma. Because of the initial definite diagnosis of cancer, a gastric resection was performed 31 days later, but no cancerous tissue was found in the resected specimen. This case was considered to be a carcinoma especially sensitive to tegafur.

Adenocarcinoma↗
PubMed1990

Immunohistochemical and histometrical studies of the human thymus with special emphasis on age-related changes in medullary epithelial and dendritic cells.

Age-related changes in medullary epithelial and dendritic cells in the human thymus were examined quantitatively using immunohistochemistry and histometry. The material used was thymic biopsy specimens obtained from 105 patients during cardiac surgery, none of whom had immunological abnormalities. By using keratin and tissue polypeptide antigen markers to identify epithelial cells and S-100 protein and LN-2 markers to identify dendritic cells, the numbers of these cells in the medulla were counted morphometrically. The relative proportions of the cortex, medulla, Hassall's bodies, perivascular space, connective tissue and fatty tissue were evaluated using a computer image-analysis system and the respective relative volumes were calculated. Our results indicate that the number of medullary dendritic cells/mm2 and the relative volume of cortical thymocytes decrease steadily up to the age of 40 years, whereas no major change was found in the number of medullary epithelial cells/mm2.

Adolescent↗
PubMed1990

Paraneoplastic encephalomyelitis. An autopsy case with encephalitis principally confined to the thalamus and associated with pulmonary and gastric cancers.

We report an autopsy case of encephalitis principally confined to the bilateral thalamus and associated with pulmonary and gastric cancers. An 81-year-old man exhibiting behavioral abnormalities and progressive somnolence died of pneumonia 11 months after onset. Because the patient had lung cancer and no definite cause of the encephalitis was found, this case was categorized as one of paraneoplastic encephalomyelitis. This may be the first reported case of this condition in which the central nervous system (CNS) lesion was located predominantly in the thalamus.

Aged↗
PubMed1990

[A case of fatal asthma induced by timolol eye-drop].

A 74 year-old man, a known asthmatic since 1972, was treated by timolol eye-drop for acute glaucoma. Several hours later the patient developed a severe attack of asthma, and died subsequently. The autopsy findings were consistent with those of typical status asthmaticus. Our patient is, to our knowledge, the first case of fatal asthma induced by timolol eye-drop in Japan.

Aged↗
PubMed1989

Further characterization of the human adrenal-derived P-glycoprotein recognized by monoclonal antibody MRK 16 reacting with only human P-glycoprotein.

This paper describes further characterization of the 170-180-kDa glycoprotein (P-glycoprotein) recognized by the monoclonal antibody MRK 16 in the human adrenal. By electron microscopy, P-glycoprotein was observed in the adrenal cell membranes. However, MRK 16-defined P-glycoprotein was not found in cow, pig, horse, monkey or rabbit adrenal, indicating that MRK 16 recognizes the non-homologous part of P-glycoprotein of various species. Eleven out of 16 adrenal tumors including 4 cases of primary aldosteronism and 7 cases of Cushing syndrome were intensely stained with MRK 16, whereas pheochromocytoma, non-functioning adrenocortical adenoma with no associated increase of serum adrenal-derived hormones and myolipoma of the adrenal were not. Finally, P-glycoprotein-MRK 16-protein A-Sepharose complex derived from human adrenal possessed marked ATPase activity. Taken together, these data suggest that P-glycoprotein may play a physiological role in the human adrenal.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1989

Primary fibrosarcoma of the liver. Immunohistochemical and electron microscopic studies.

An autopsy case of primary fibrosarcoma occurring in the liver of a 75-year-old female is presented. The tumor, arising from the lateral upper portion of the right lobe, measured 14 cm in greatest dimension. Light microscopy of the tumor revealed homogeneous, spindle-shaped cells with abundant collagen fibers showing a classic herring-bone pattern. Immunoreactive vimentin was found in the tumor cells. Electron microscopically, the tumor cells were rich in rough endoplasmic reticulum without a basement membrane, and were surrounded by large amounts of collagen fibers. The fibroblastic character of the tumor cells was suggested by light and electron microscopy. This may be the first reported case of primary hepatic fibrosarcoma examined by immunohistochemistry and electron microscopy.

Aged↗