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Biomedical subjects

H Nagura

Publications and source records attributed to H Nagura.

At least 19 recordsLinked to original sources
PubMed1996

Expression of prohormone convertase, PC2, in adrenocorticotropin-producing thymic carcinoid with elevated plasma corticotropin-releasing hormone.

An autopsy case of ACTH-producing thymic carcinoid with Cushing's syndrome is reported. The patient was a 63-yr-old man with multiple bone metastases from an undetermined primary site. Hyperpigmentation was observed at the terminal stage. The plasma levels of ACTH, cortisol, chromogranin A, and urinary 17-hydroxy-corticosteroids were extremely high, and ectopic ACTH-producing neuroendocrine tumor was diagnosed. In addition, plasma CRH was high. Autopsy revealed that the patient had primary thymic carcinoid with extensive metastases. Remarkable hyperplasia of the adrenal cortexes and Crooke's hyaline degeneration of the pituitary gland were consistent with Cushing's syndrome by ectopic ACTH production. There were multiple CRH-producing cells without degenerative changes in the hypothalamus. The tumor cells were immunoreactive to ACTH, CRH, and the cleavage enzyme PC2. POMC messenger ribonucleic acid and PC2 messenger ribonucleic acid were detected in the tumor cells by an in situ hybridization method. Expression of PC2 was considered to induce hyperpigmentation by producing alpha MSH. Despite hypercortisolism and ectopic production of CRH by the tumor cells, hypothalamic CRH cells were not atrophic. This case is a good example to demonstrate the correlation between CRH and the hypothalamo-pituitary-adrenal axis as well as hyperpigmentation in Cushing's syndrome.

Adrenocorticotropic Hormone↗
PubMed1995

Expression of urokinase receptor in various stromal-cell populations in human colon cancer: immunoelectron microscopical analysis.

The host reaction is an important factor in the biological behavior of cancers. In human colon adenocarcinoma, stromal cells and some cancer cells express the urokinase receptor (uPAR), a molecule involved in the regulation of extracellular proteolysis. The present study reveals the identity of uPAR-expressing cell types and the subcellular localization of this molecule by immunoelectron microscopy in colon cancer. uPAR-positive cells were most abundant at the invasive margin of colon cancer and were identified as macrophages, fibroblasts, neutrophilic and eosinophilic granulocytes, endothelial cells and cancer cells. Of these, the most numerous were macrophages with uPAR detected along the plasma membrane, in accordance with its function in plasminogen activation on the cell surface. Fibroblasts were labeled in the lumen of rough endoplasmic reticulum, indicating its intracellular synthesis. Some granulocytes and endothelial cells expressed immunoreactivity along the plasma membrane. uPAR-positive cancer cells were stained along the plasma membrane and in rough endoplasmic reticulum. These findings suggested that a variety of non-malignant host cells play an important role in the plasmin-mediated breakdown of the extracellular matrix at the invasive margin.

Adenocarcinoma↗
PubMed1995

Accumulation of plasma cells in atherosclerotic lesions of Watanabe heritable hyperlipidemic rabbits.

By screening a cDNA library constructed from aortic total RNA derived from Watanabe heritable hyperlipidemic (WHHL) rabbits by differential hybridization, we have obtained a cDNA encoding the kappa light chain of immunoglobulin. Northern blot analysis of total RNA prepared from aortas of WHHL and normal rabbits of various ages revealed that this light-chain mRNA accumulates gradually with age in aortas in WHHL rabbits. Northern blotting and in situ hybridization with an antisense oligonucleotide specific to rabbit immunoglobulin gamma heavy-chain mRNA also detected accumulation of this heavy-chain mRNA in advanced lesions of WHHL rabbit aortas. Moreover, immunohistochemical and electron microscopic analyses demonstrated the presence of plasma cells in the atherosclerotic lesions.

Amino Acid Sequence↗
PubMed1995

Immunohistochemical study of gamma delta T cell receptor-positive cells in the capsular region of hepatocellular carcinoma: possible role in defense against expansion of carcinoma in the liver.

The localization and distribution of gamma delta T cell receptor (TCR)-positive cells (gamma delta T cells) in hepatocellular carcinoma capsules was investigated immunohistochemically at both light and electron microscopic levels. Most of the mononuclear cells infiltrating the tumor capsules were CD3-positive. Together with gamma delta T cells, they were significantly increased in the tumor capsules compared to amounts in the fibrous septa in non-cancerous cirrhotic areas of the same liver, and compared to amounts in the liver of patients with cirrhosis. Phenotypic characterization by the two-color double-staining technique showed that CD8/gamma delta cells were significantly increased in the tumor capsule, and that more than one-third of gamma delta TCR-positive cells also expressed the CD56 antigen. Morphological observation revealed that large gamma delta T cells were increased in number in the tumor capsule and that the cytoplasm of these cells contained multivesicular bodies and dense granules. These morphological features were similar to those of large granular lymphocytes, and most of the gamma delta T cells were also positive for BB3. This suggests that extrathymic maturation of gamma delta T cells occurs in the tumor capsule, and that these gamma delta T cells may have a cytolytic effect on tumor cells, as shown in large granular lymphocytes; further, the results suggest that these cells may play a role in the defense against tumor expansion.

Aged↗
PubMed1995

Transcription factor adrenal 4 binding protein as a marker of adrenocortical malignancy.

Adrenal 4 binding protein (Ad4BP) is a transcription factor that regulates the expression of the steroidogenic enzymes and is expressed primarily in steroidogenic cells. We immunolocalized Ad4BP in adrenocortical carcinoma (eight cases) and various malignancies that histologically simulate an adrenocortical carcinoma to evaluate the value of Ad4BP as an immunohistochemical marker of adrenocortical carcinoma. These malignancies examined were renal cell carcinoma (20 cases), hepatocellular carcinoma (10 cases), malignant melanoma (eight cases), ovarian (six cases) and uterine (three cases) clear cell carcinoma, large cell carcinoma of the lung (five cases), and pheochromocytoma (three cases). Nuclear Ad4BP immunoreactivity was observed only in adrenocortical carcinoma cases but not in other tumors examined. Almost all of the adrenocortical carcinoma cells were immunohistochemically positive for Ad4BP including cells associated with bizarre nuclei. These results show that application of Ad4BP immunostain can contribute greatly to the differential diagnosis of adrenocortical carcinoma.

Adrenal Cortex Neoplasms↗
PubMed1995

Adrenocortical cytopathology.

Cytopathologic smears and/or imprints of human adrenal cortex (9 cases) and its disorders were examined, including adrenocortical nodule (3 cases), adrenocortical adenoma (23 cases), carcinoma (8 cases), and renal cell carcinoma (6 cases). Immunocytochemistry directed against 3 beta-hydroxysteroid dehydrogenase and adrenal-4-binding protein (Ad4BP), a transcription factor in steroidogenesis, was also performed. There were no cytologic differences between normal adrenal and adrenocortical nodules. Large nuclei with prominent nucleoli were observed predominantly in adrenocortical neoplasms. Cellular atypia or pleomorphism and the degree of cohesiveness were unreliable criteria in differentiating between adrenocortical adenoma and carcinoma. Mitosis and necrotic materials were observed only in adrenocortical carcinoma. These cytologic findings were considered contributory, but not diagnostic when evaluating adrenocortical disorders because of marked intra-tumoral heterogeneity. There were no reliable cytologic criteria in differentiating adrenocortical and renal cell carcinoma. Immunocytochemistry of 3 beta-hydroxysteroid dehydrogenase and especially Ad4BP was demonstrated to aid greatly in the differential diagnosis between these carcinomas by identifying adrenocortical parenchymal cells.

3-Hydroxysteroid Dehydrogenases↗
PubMed1995

Cell adhesion molecule expression by vascular endothelial cells as an immune/inflammatory reaction in human colon carcinoma.

The cell adhesion of inflammatory cells to vascular endothelial cells is an important process in the recruitment of inflammatory cells to the site. In cancer tissue, infiltration of inflammatory cells has been suggested to be a mechanism of host resistance. To clarify this infiltration mechanism, we investigated cell adhesion molecule expression (E-selectin, P-selectin, and ICAM-1) in vascular endothelial cells by immunohistochemistry in colon carcinoma. Venules distributed along the invasive margin expressed E- and P-selectins and ICAM-1. These phenotypical features are identical to those of endothelial cells observed in active inflammatory lesions, and the vessels can, therefore, be designated as immunologically activated vessels. Nevertheless, the majority of blood vessels within the tumor lacked immunoreactivity for all these adhesion molecules and, therefore, could be designated as immunologically inactive vessels. Granulocytes, lymphocytes and macrophages, bearing the counter-receptors of these adhesion molecules, were more densely distributed along the invasive margin. In contrast, few inflammatory cells were present within the tumor. In conclusion, the present study has demonstrated the phenotypical heterogeneity of tumor vessels; those for inflammatory cell infiltration to the tumor and those for the nutrient supply to the tumor.

Cell Adhesion↗
PubMed1995

Immunoelectron microscopic localization of gelatinase A in human gastrointestinal and skin carcinomas: difference between cancer cells and fibroblasts.

Previous reports revealed a discrepancy in gelatinase A localization in human cancers; i.e., protein localization in cancer cells and mRNA localization in stromal fibroblastic cells. To clarify this, we conducted immunoelectron microscopic study of gelatinase A in cancer and stromal cells in human gastrointestinal and skin carcinomas. Although both carcinoma cells and fibroblasts were positive for gelatinase A, the subcellular localizations were different. On immunoelectron microscopy, fibroblasts showed immunoreactivity in the lumen of the rough endoplasmic reticulum (rER) or in the cytosol on the surface of rER, demonstrating synthesis of the protein. Carcinoma cells showed diffuse deposition of gelatinase A in the cytosol, suggesting the accumulation of the antigen both in adenocarcinoma and squamous cell carcinoma. Immunoreactivity along the cell membrane was demonstrated in one case of skin carcinoma. Macrophages showed also diffuse deposition of gelatinase A in the cytosol. In conclusion, we found a qualitative difference of gelatinase A localization between carcinoma cells and fibroblasts, and concluded that carcinoma cells may not be important in the secretion of gelatinase A.

Adenocarcinoma↗
PubMed1995

Similarities of in situ mRNA expression between gelatinase A (MMP-2) and type I procollagen in human gastrointestinal carcinoma: comparison with granulation tissue reaction.

The mRNA localizations of gelatinase A(MMP-2) and type I carcinoma and non-neoplastic fibrous granulation tissue were compared. By in situ hybridization, gelatinase A was shown to be expressed in fibroblasts not only in cancer stroma but also in the "reactive fibrosis zone," which surrounds the invasive margin of cancer. In most cases, no accentuation of gelatinase A expression was observed in the invasive margin. This localization pattern of gelatinase A was essentially the same as that of type I procollagen. In gastric cancer associated with deep ulceration, gelatinase A was more abundantly expressed in fibroblastic cells in granulation tissue of the ulcer base than in cancer stroma. The same situation was found in non-neoplastic fibrous granulation tissue, in which fibroblasts abundantly expressed mRNAs for both gelatinase A and type I collagen. Scar tissue (old fibrotic lesion) showed diminished expression of mRNAs for both gelatinase A and type I procollagen. The localization patterns suggest another function of gelatinase A in cancer tissue as a turnover enzyme of the extracellular matrix.

Colonic Neoplasms↗
PubMed1995

Intercellular adhesion molecule-1 expression by macrophages in human gastrointestinal carcinoma: possible roles as host immune/inflammatory reaction.

Tumor-associated macrophages (TAM) are one of the factors which modulate the carcinoma progression. The present study described immunohistochemical expression of intercellular adhesion molecule-1 (ICAM-1) in stromal cells in human gastrointestinal carcinoma identifying the cell types by immunoelectron microscopy. In colon and gastric carcinomas, ICAM-1-positive cells were mostly stromal cells, and major cell types were identified as macrophages and fibroblasts by immunoelectron microscopy. Macrophages were characterized by their ovoid shape, cytoplasmic projections, abundant vacuoles, phagocytosis, and paucity of rough endoplasmic reticulum. Fibroblasts contained stacks of rough endoplasmic reticulum. Macrophages were major cells among ICAM-1-positive cells along the invasive margin, while fibroblasts were predominant in the stroma within carcinoma in colon and intestinal-type gastric carcinomas. Lymphocytes positive for lymphocyte function associated antigen (LFA-1), a counter-receptor of ICAM-1, were densely distributed along the invasive margin, and sparsely in the stroma within carcinoma. In diffuse-type gastric carcinoma, most macrophages were dendritic-shaped and negative for ICAM-1. Our study suggests that the invasive margin is an area similar to active inflammation, where the antigen presenting cells (macrophages) and lymphocytes may interact via the ICAM-1/LFA-1 adhesion.

Carcinoma↗
PubMed1995

Transient hepatic fibrin-ring granulomas in a patient with acute hepatitis A.

A case of acute hepatitis A associated with fibrin-ring granulomas in the liver is presented. Because a relationship between acute hepatitis A infection and granuloma formation had not previously been established, liver specimens were examined from both the hepatitic and recovery phases. Numerous fibrin-ring granulomas were observed in the parenchyma during the hepatitic phase. The cellular components of the granulomas were largely macrophages and CD4-positive T-cells. Granulomas had disappeared completely by the recovery phase. These results suggest that fibrin-ring granulomas were caused by hepatitis A virus infection. This virus may activate macrophages and CD4-positive T-cells through an as-yet undetermined mechanism.

Acute Disease↗
PubMed1995

Ad4BP in the human adrenal cortex and its disorders.

Ad4BP, a zinc finger DNA-binding protein, is a transcription factor that regulates the expression of the steroidogenic P450 genes. We performed immunoblotting and immunohistochemistry of Ad4BP in 34 human adrenal cortex specimens, which included adrenocortical adenomas and carcinomas. Immunoblotting revealed a single band of 53K, corresponding to the mol wt of Ad4BP. The immunohistochemical studies demonstrated that Ad4BP immunoreactivity was present exclusively in the nuclei of nearly all of the adrenocortical parenchymal cells in both the normal and the pathological human adrenal specimens. Ad4BP was immunostained with equal intensity and frequency among the different cell types. Ad4BP immunoreactivity was also observed in areas of marked degenerative changes, such as lipomyelomatous lesions, and in poorly differentiated carcinoma cells. These results suggest a close association of Ad4BP expression with the biological phenotype of adrenocortical parenchymal cells. Ad4BP therefore seems to play important roles in the induction and maintenance of the transcription of all steroidogenic P450 genes in human adrenocortical cells, even after malignant transformation.

Adenoma↗
PubMed1995

[A case of closed head injury with diffuse axonal injury, and oculomotor nerve avulsion and midbrain infarction].

We report an autopsy case of 66-year-old woman with closed head injury due to a fall from stairs. She had recovered after a half day period of coma following the fall. Severe right peripheral oculomotor nerve palsy was noted from the beginning. MRI demonstrated lesions in the corpus callosum and right midbrain. She had died of suffocation due to sputum impaction after 50 hours after the fall. Autopsy examination revealed traumatic subarachnoidal hemorrhage, partial tearing and petechial hemorrhage of the corpus callosum, and many axonal retraction balls scattered in the cerebral white matter. Avulsion of the right oculomotor nerve root and fresh midbrain infarct with hemorrhage in the territory of right paramedian artery were observed. Axonal retraction balls were densely distributed in the periphery of midbrain infarct. The distribution pattern of axonal retraction balls in the cerebrum was similar to that of damage due to shear strain in Holbourn's gelatin model of closed head injury. The midbrain infarct and oculomotor nerve avulsion may be due to both mechanical and ischemic damage during and after the fall. All of the lesions described above may be closely related to the rotatory force from the right forehead.

Aged↗
PubMed1995

Cell proliferation and apoptosis in normal and pathologic human adrenal.

Cell proliferation and programmed cell death play important roles in the maintenance of tissue dynamics. The adrenal cortex has been known as a cell renewal tissue. We studied cell proliferation by Ki67 immunostaining and programmed cell death or apoptosis by a recently developed 3'-OH nick end labeling technique. Fifteen cases of normal human adrenal; 22 cases of adrenocortical adenoma including Cushing's adenoma (five cases), aldosteronoma (nine cases), and nonfunctioning adenoma (eight cases); and six cases of adrenocortical carcinoma were examined. In normal adrenal cortex, Ki67 immunoreactivity was predominantly observed in the zona fasciculata in all the cases examined, whereas cortical cells positive for nick end labeling were present in the zona reticularis in all cases and in the zona glomerulosa in five cases. These results suggest that the "cell migration" or "centripetal" theory is also applicable in cell turnover of normal human adrenal cortex, and cortical cells may move in two directions, from fasciculata to reticularis and from fasciculata to glomerulosa in some instances. CD68-positive sinusoidal lining cells, which are considered to ingest the cells undergoing apoptosis, were present throughout the cortex. In adrenocortical adenoma, Ki67 immunoreactivity was observed in all cases, and tumor cells positive for nick end labeling were observed in 12 cases (Cushing's adenoma in three cases, aldosteronoma in four cases, and nonfunctioning adenoma in five cases). In adrenocortical carcinoma, Ki67 immunoreactivity was observed in all the cases, and its labeling index was significantly higher than that of normal adrenal and adrenocortical adenoma.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Gland Neoplasms↗
PubMed1995

[Hemorrhagic cerebral infarction at the old age in a case with familial antithrombin III (ATIII) deficiency].

An old woman had stroke at age 67. Cerebral CT scan disclosed the low-density lesion with high-density area in the left temporal lobe, but no empty delta sign in the superior sagittal sinus. Thereafter, she had sometimes panic attacks. At the age of 70, she was admitted because of loss of consciousness probably caused by the same attack. On admission, Brain CT scan showed no fresh lesions. During the stay in the hospital, she had an episode of deep vein thrombosis of her left leg. The patient was found to have not only reduced biochemical activity but also low immunological level of AT III. Her nephew had also the low plasma AT III antigen concentration. Transesophageal echocardiography showed no abnormality, but atherosclerotic change at the aortic arch. We speculated that hemorrhagic cerebral infarction in the territory of the branch of middle cerebral artery could be induced by the arterial thrombus which was related to the hypercoagulable state associated with familial AT III deficiency, although the possibility of cardiogenic embolic infarction or of cerebral vein thrombosis could not be ruled out. Familial AT III deficiency is one of the causes of cerebral infarction even in the elderly.

Aged↗
PubMed1995

Histological classification of the neoplastic changes arising in ulcerative colitis: a new proposal in Japan.

Patients with total ulcerative colitis with a longstanding course of the disease have a high risk of developing colorectal carcinoma. Colonoscopic surveillance to detect precancerous tissue and/or cancer in these patients has been carried out in countries with a high incidence of ulcerative colitis. Riddell's classification has been widely used for the interpretation of biopsy specimens obtained from the colonoscopic surveillance. In Japan, however, there are problems in accepting Riddell's classification, mainly because the intramucosal carcinomas diagnosed by Japanese histopathologists are included in the category of high-grade dysplasia in Riddell's classification. Based on the results of a meticulous slide review carried out by seven histopathologists in this study, a new classification is proposed: UC-I, inflammatory change; UC-II, indefinite; UC-IIa, probably inflammatory; UC-IIb, probably neoplastic; UC-III, neoplastic but not carcinomatous; and UC-IV, carcinoma. Intramucosal carcinomas is included in the category UC-IV. We consider that the diagnosis of intramucosal carcinoma is to be made when there is a high grade of cytological and structural atypia consistent with carcinoma. Interobserver and intraobserver variability with this classification was acceptable. We believe this new classification will be widely use in cancer surveillance in ulcerative colitis in Japan.

Biopsy↗