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Biomedical subjects

Y Hamashima

Publications and source records attributed to Y Hamashima.

At least 55 records · Page 3Linked to original sources

Immunohistochemical localisation of vitamin B12 R-binder in the human digestive tract.

The distribution of vitamin B12 R-binder in the human digestive tract was studied using an indirect immunoperoxidase technique. Positive staining for R-binder was found in the mucous cells and ductal epithelial cells of the salivary glands and the oesophageal glands. In normal gastric mucosa, no positive staining for R-binder was found, but in the area with intestinal metaplasia, the columnar epithelial cells and goblet cells showed positive staining. Epithelial cells of the gallbladder, intrahepatic bile ducts and pancreatic ducts were also positive for R-binder. In the small intestine and colon, R-binder was found in the columnar epithelial cells and goblet cells. The measurement of unsaturated vitamin B12 binding capacity and cobalamin content in the extracts from intestinal mucosa also indicated the presence of R-binder in the intestinal mucosa.

Adult↗

Clinicopathological study of patients with mesangial isolated C3d deposition in various glomerular diseases.

The clinicopathological findings of isolated mesangial C3d deposition in the absence of other complement components or immunoglobulins are summarized. 55 out of 242 individual human renal biopsies examined by immunoperoxidase microscopy had isolated C3d deposition. This group consisted of 12 patients with chronic glomerulonephritis, 8 with minimal-change nephrotic syndrome, 32 with benign recurrent hematuria, 2 with Bartter's syndrome and 1 with Raynaud's syndrome. None of these patients had a disorder of the renal function and in all the patients the disease took a benign clinical course. Light-microscopic findings indicated injuries ranging from minor glomerular abnormality to mild diffuse mesangial proliferative glomerulonephritis, and there were no other remarkable findings such as cellular crescents, global sclerosis or interstitial infiltration. By immunoperoxidase microscopy, fine granular deposits of C3d were identified only in the mesangium, and arteriolar C3 staining was seen in 31 of the 55 patients. In 38 of the 42 patients examined by electron microscopy, electron-dense deposits were identified in the mesangial matrix. These findings suggest that isolated C3d deposition is a new entity with benign features both clinically and pathologically.

Adolescent↗

Quantitative analysis of narrowings of intramyocardial small arteries in normal hearts, hypertensive hearts, and hearts with hypertrophic cardiomyopathy.

To clarify the pathophysiologic role of intramyocardial small artery (IMSA) diseases in hypertrophied hearts, narrowings of the IMSA were quantitatively evaluated in 39 autopsied hearts, 10 from patients with typical hypertrophic cardiomyopathy (HCM), four from patients with HCM showing features mimicking dilated cardiomyopathy (DCM-like HCM), 10 from patients with hypertension, and 15 from normal adults. The relations of narrowings of the IMSA to myocytic hypertrophy, myocardial fiber disarray, and fibrosis were also examined. The external caliber and the ratio of the luminal area to the total vascular area (percent luminal area, % lumen) were calculated by an image analyzer in 85 to 203 IMSAs from each patient. The external calibers of the IMSAs were similar among groups of hearts with HCM, hypertensive hearts, and normal hearts but were greater in those with DCM-like HCM. The mean % lumen of the IMSAs was similarly reduced in the hearts with HCM (29 +/- 5% in the ventricular septum and 31 +/- 5% in the left ventricular free wall) and in hypertensive hearts (30 +/- 8% and 31 +/- 7%) compared with that in normal hearts (40 +/- 5% and 38 +/- 5%) and was the lowest in the ventricular septum of hearts with DCM-like HCM (17 +/- 3%). The mean % lumen of the IMSA was inversely correlated with heart weight (r = -.59), the mean size of myocytes (r = -.66 in the ventricular septum, r = -.63 in the free wall), and percent fibrotic area in the septum (r = -.68). The mean % lumen values of the IMSAs in the tissues with and without disarray in the hearts with HCM were similar. Thus IMSA disease is of pathophysiologic importance in patients with HCM, DCM-like HCM in particular, or with hypertension.

Adult↗

Quantitative analysis of infarct size, contraction band necrosis, and coagulation necrosis in human autopsied hearts with acute myocardial infarction after treatment with selective intracoronary thrombolysis.

To assess the importance of contraction band necrosis (CBN) in patients with acute myocardial infarction (AMI) treated with selective intracoronary thrombolysis, CBN, coagulation necrosis, and infarct size (expressed as CBN + coagulation necrosis) were analyzed quantitatively in 16 autopsied hearts. Intracoronary thrombolysis was performed from 2 to 6 hr after the onset of AMI, and the time from the onset of AMI to death was 7 to 168 hr. Cineangiography revealed no evidence of good collateral circulation in any of the patients. The 16 patients were classified into three groups: six patients with successful thrombolysis (100% to 99% stenosis, group I), five patients with unsuccessful thrombolysis (100% to 100%, group II), and five patients with 99% stenosis before thrombolysis (group III). Among the three groups, there were no significant differences in the time from the onset of AMI to thrombolysis, the time from the onset of AMI to death, the cause of death, or the degree of collateral circulation. The percentage of the risk area involved by the infarct in group I (82 +/- 6%) was similar to that in group II (80 +/- 11%). Infarct size was not reduced in group I because collateral circulation was not good and because the degree of recanalization after thrombolysis was 1%. However, the percentage of the infarct area with CBN was significantly higher in group I (20 +/- 9%) then in group II (3 +/- 3%). This finding shows that diffuse CBN occurred after reperfusion in patients with AMI treated with thrombolysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Distribution of vitamin B12 R binder in normal human tissues: an immunohistochemical study.

We studied the distribution of vitamin B12 R binder in various normal human tissues by use of an immunoperoxidase technique. Positive staining for R binder was observed in almost all glandular epithelia of digestive system, bronchial glands, renal proximal tubules, prostate, uterus, Fallopian tube, mammary gland, and sweat glands. The distribution of R binder was similar to that of lactoferrin and secretory component. These findings support the hypothesis that R binder plays a role in the local defense mechanism.

Digestive System↗

Pathogenetic role of myocardial fiber disarray in the progression of cardiac fibrosis in normal hearts, hypertensive hearts and hearts with hypertrophic cardiomyopathy.

To define the pathogenetic role of myocardial fiber disarray in the progression of cardiac fibrosis, the percent area of fibrosis in tissue with disarray was compared with that in tissue without disarray. Thirty autopsied hearts, 10 from patients with hypertrophic cardiomyopathy, 10 from patients with hypertension and 10 from normal adults, were studied. The percent areas of fibrosis in tissues with and without disarray were significantly different (p less than 0.01) among hearts with hypertrophic cardiomyopathy (12.6 +/- 4.0 and 8.2 +/- 3.3%), hypertensive hearts (6.6 +/- 3.6 and 2.5 +/- 1.4%) and normal hearts (2.8 +/- 1.2 and 1.0 +/- 0.4%). The percent area of fibrosis in tissue with disarray was greater than in that without disarray in all 3 groups and the ratios of these percentages were similar in the 3 groups: 2.9 +/- 4.2 in hypertrophic cardiomyopathy 2.5 +/- 1.7 in hypertensive hearts and 2.5 +/- 1.8 in normal hearts. The conclusions are: 1) disarray promotes fibrosis to a similar degree, not only in hypertrophic cardiomyopathy, but also in hypertensive hearts and normal hearts; 2) the increased level of fibrosis in hearts with hypertrophic cardiomyopathy and in hypertensive hearts, together with widespread fibrosis in hearts with hypertrophic cardiomyopathy in particular cannot be explained by disarray alone.

Cardiomegaly↗

Morphological features of hypertrophic cardiomyopathy with congestive heart failure and a small left ventricular cavity.

To clarify the morphologic basis of marked congestive heart failure in cases of hypertrophic cardiomyopathy with a small left ventricular cavity, the size of myocytes, the extent of myocardial fiber disarray and fibrosis were quantitatively evaluated in two autopsied cases. Compared with the control hypertrophic cardiomyopathy, both cases had larger myocytes and less fibrosis, and one of them had markedly extensive myocardial fiber disarray. Probably, the hypertrophy of the myocytes or myocardial fiber disarray or both rather than myocardial fibrosis are important in the pathogenesis of severe congestive heart failure in these cases.

Adult↗

Thymic rudiments are responsible for induction of functional T cells in nu/nu mice.

Congenitally athymic nude (nu/nu) mice have been thought to exhibit no T cell functions despite the presence of some Thy-1 positive (Thy-1+) cells. However, we detected a significant number of Con A-responsive cells in spleens of nu/nu mice after the age of 2 months when the spleen cells were cultured in a medium containing 5% human plasma or human serum, but not when they were cultured in fetal calf serum. Cytotoxic test using anti-Thy-1.2 antibody plus complement has revealed that these Con A-responsive cells are indeed Thy-1+. The Con A-responsive T cells increase with age. PHA-responsive and alloreactive T cells are also detected in the spleens of 11-month-old nu/nu mice. To probe the origins of the T-lymphocytes of the nu/nu mice we examined extensively and systematically the thymic remnants in the mediastinum and neck region of the nu/nu mice in search for T cell development in thymic rudiments. In these investigations we regularly found small accumulations of cells comprising almost entirely Thy-1+ lymphocytes surrounding accumulations surrounded by epithelial cells. These findings suggest that apparent sites of T cell development in thymic rudiments are indeed present in nude mice and appear to be functioning to induce expression T cell markers on precursor cells in the lymphoid lineage. Together with our prior findings the evidence presented in this report shows that a pathway exists in nude mice. In the converse these findings suggest that the thymus is the sole site for induction of the differentiation of stem cells or precursor T cells into mature T-lymphocytes. The findings suggest that indications of alternative differentiation pathways for T-lymphocytes must seek the location of these pathways within the thymus itself.

Aging↗

Treatment of systemic and organ-specific autoimmune disease in mice by allogeneic bone marrow transplantation.

Autoimmune diseases have been clinically divided into those which are systemic and organ-specific. (NZB X NZW) F1, MRL/1, and BXSB mice have been utilized as models for systemic autoimmune diseases. When these mice which had already developed autoimmune diseases were irradiated and reconstituted with T cell-depleted allogeneic bone marrow cells, the recipient survived for more than 5 months without showing graft-versus-host reaction. Immunohistopathological studies revealed that deposits of immunoglobulin and complement into the glomeruli were markedly reduced. In addition, levels of circulating immune complexes and auto-antibodies such as anti-dsDNA and anti-Sm antibodies decreased. Three months after bone marrow transplantation, T cell dysfunction was restored, and hyperfunction of B cells and macrophages were normalized. These data prompted us to examine whether or not organ-specific autoimmune diseases can be treated by allogeneic bone marrow transplantation. NOD mice which develop insulitis and overt diabetes were used for this experiment. The mice showed marked infiltration of T cells into the pancreatic islets which resulted in selectively destroying beta cells. Most of the T cells are Lyt-1+, and some are Lyt-2,3+. When NOD mice (6 months old) were irradiated and reconstituted with bone marrow cells of young BALB/c nu/nu mice (less than 2 months), the NOD mice exhibited neither insulitis nor overt diabetes. Deposits of immunoglobulin in the mesangial area of the glomeruli disappeared 3 months after bone marrow transplantation. Assays for immunological functions revealed that NOD mice showed hyperfunction of T cells, B cells, and macrophages. In NOD mice reconstituted with BALB/c nu/nu bone marrow cells, these functions were normalized. Newly developed T cells are found to be tolerant of both bone marrow donor-type and host-type major histocompatibility complex determinants. These results suggest that bone marrow transplantation is a strategy to be considered as an approach to the treatment for both systemic and organ-specific autoimmune diseases in humans.

Animals↗

Quantitative analysis of myocardial infarction in (NZW x BXSB)F1 hybrid mice with systemic lupus erythematosus and small coronary artery disease.

Male (NZW x BXSB)F1 mice ([W x B]F1) were used as a model for small coronary artery disease. The mortality rate for 162 mice was 0% at 12 weeks and 37% at 24 weeks. The incidence of myocardial infarction (MI) was 0% at 12 weeks, 22% at 16 weeks, 39% at 20 weeks, and 53% at 24 weeks. In 29 of the 35 (W x B)F1 male mice with MI, small multiple infarctions were noted in the right ventricular free wall and anterior, lateral, posterior, and septal ventricular walls. In 25 of the 29 hearts with multiple infarcts, the infarcts in the same heart were at the same histologic stage. Twenty-one of these hearts showed only replacement fibrosis, and 4 hearts showed only granulation. The remaining 4 hearts with multiple infarcts exhibited coagulation necrosis plus fibrosis or granulation. Quantitative analysis of the infarct size revealed that in the 35 (W x B)F1 males with MI, the relative area of MI (%MI) was significantly larger in the right ventricular free wall (6.7% +/- 8.4%) than in the ventricular septum (1.9% +/- 2.4%) or in the left ventricular free wall (2.1% +/- 2.5%). The %MI was greatest in the right third (3.6% +/- 5.4%) of the ventricular septum and in the outer third (2.9% +/- 3.3%) of the left ventricular free wall. The %MI did not increase with age. In 11 of the 35 (W x B)F1 mice, 27 intramural small arteries showed marked obliterative lesions. Most of them were in the right ventricular free wall, the right third of the ventricular septum, or the outer third of the left ventricular free wall. There was no evidence of stenosis in the extracardiac major coronary arteries. In addition, the infarct showed a whirlpool-like configuration, and x-ray photographs revealed that the small intramural coronary arteries had a whirlpool-like configuration. It is concluded that in (W x B)F1 males multiple small infarcts appear at the same time due to small coronary artery disease. The whirlpool configuration of the infarct reflects the special anatomy of the intramural coronary arteries in the mice.

Animals↗

Immunohistochemical localization of the actin in the healing stage of gastric ulcers.

Healing gastric ulcers were examined immunohistochemically for the presence of myofibroblasts containing actin microfilaments. Twenty five surgical specimens of the gastric ulcer corresponding to the initial healing stage and the proliferative healing stage, and 30 surgical specimens of the acetic acid-induced ulcers in rats at 3, 8 (initial healing stage), and 15 (proliferative healing stage) days after ulcer induction were fixed and cut into 4-micron sections, which were then treated with anti-actin serum, peroxidase-antiperoxidase and incubated for the localization of actin. Controls were prepared using non-immune serum or preabsorbed immune serum. Actin-positive fibroblasts were seen at the edge and the floor of the ulcer in the initial healing stage, but not in the edge of the ulcer in the proliferative healing stage. Such cells may be responsible for the contraction of the ulcer caliver observed clinically in the initial healing stage of the gastric ulcer.

Actins↗

Distribution of collagen type IV in soft tissue tumors. An immunohistochemical study.

The distribution of collagen type IV, one of the major constituents of basement membrane, was studied immunohistologically in a series of 103 soft tissue tumors including those of peripheral nerve origin, smooth muscle origin, striated muscle origin, fibrous tissue origin, fibrohistiocytic origin, adipose tissue origin, synovial tissue origin, and blood vessel origin, paragangliomas, alveolar soft part sarcomas, granular cell tumors, and epithelioid sarcomas. Intensely positive staining for collagen type IV was observed in neurilemomas, neurofibromas, malignant schwannomas, and blood vessel tumors. Weakly to moderately positive staining was seen in leiomyomas, angiomyomas, and leiomyosarcomas. In contrast, synovial, fibroblastic and fibrohistiocytic tumors, benign or malignant, were negative. In paragangliomas, granular cell tumors, and alveolar soft part sarcomas, positive staining was evident surrounding nests or clusters of tumor cells. In all tumors, staining for collagen type IV clearly illustrated the vascular pattern.

Collagen↗

Comparison of macroscopic, postmortem, angiographic and two-dimensional echocardiographic findings of coronary aneurysms in children with Kawasaki disease.

To assess why the results of 2-dimensional echocardiography (2-D echo) for diagnosis of coronary aneurysm in patients with Kawasaki disease differed from those of cineangiography, the macroscopic, postmortem, angiographic and 2-D echocardiographic findings of 8 autopsied hearts of infants and children with Kawasaki disease were compared. Postmortem angiography and 2-D echo yielded similar results in aneurysms in which there was no thrombus, organization or marked thickening of the arterial wall. However, in aneurysms with complete or incomplete occlusion of the dilated cavity due to thrombi, organization or marked thickening of arterial wall, angiographic results reflected only the free cavity of the coronary aneurysm, but could not detect the original aneurysm. Two-dimensional echocardiography disclosed an echo-free space representing the original aneurysm, in which some materials, suggesting thrombi or organization, were found. However, it did not reveal whether the aneurysm was occlusive. This finding indicates that the discrepancies between the results of cineangiography and 2-D echo are attributable to the formation of large thrombi, organization or marked thickening of the arterial wall in the aneurysmal cavity. It is clinically important to know these limitations of angiography and 2-D echo.

Angiocardiography↗

Evaluation of anti-cardiolipin antibody and its cross-reactivity in sera of patients with lepromatous leprosy.

Using a sensitive and modified solid-phase radioimmunoassay for detecting anti-cardiolipin antibodies, sera of 45 patients with lepromatous leprosy were examined. Nine of the 45 (20%) showed positive levels of anti-cardiolipin antibodies. Inhibition tests revealed that these antibodies significantly cross-reacted with double-stranded (ds) DNA, but not with single-stranded (ss) DNA or extractable nuclear antigens (ENA). We describe the unique pattern of antibody cross-reactivity with cardiolipin and dsDNA in sera of patients with lepromatous leprosy.

Antigens, Nuclear↗