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Biomedical subjects

M Hirokawa

Publications and source records attributed to M Hirokawa.

At least 91 records · Page 5Linked to original sources

Endothelins promote egg albumin-induced intestinal anaphylaxis in rats.

BACKGROUND & AIMS: The basic mechanisms of food allergies are still unknown. The aims of this study were to investigate whether endothelins (ETs) in the intestinal mucosa are involved in the pathogenesis of intestinal anaphylaxis. METHODS: Sprague-Dawley rats were sensitized to chicken egg albumin (EA) by intraperitoneal injection. Fourteen days after sensitization, EA was administered in the jejunal segments to induce intestinal anaphylaxis. Net water outflux and histamine release into loops and serum concentrations of rat mast cell protease II (RMCP-II) were determined. ET-1 and ET-3 concentrations in the jejunal mucosa were determined, and expression of the corresponding messenger RNAs was examined by competitive polymerase chain reaction. RESULTS: In sensitized animals, challenge with intraluminal antigen caused a significant increase in net water outflux and histamine release together with an elevation of serum RMCP-II concentrations. Mucosal concentrations of ET-1 and ET-3 and expression of their messenger RNAs were significantly increased in sensitized animals after EA challenge. Treatment with an ETA-receptor antagonist, but not an ETB-receptor antagonist, attenuated the increase in net water outflux, histamine release, and serum RMCP-II concentrations in rats with EA-induced intestinal anaphylaxis. CONCLUSIONS: Release of ETs in the intestinal mucosa increased in sensitized animals after EA challenge. ETs may play a significant role in the development of intestinal anaphylaxis via an ETA receptor.

Albumins↗

Determination of antipituitary antibody in patients with endocrine disorders by enzyme-linked immunosorbent assay and Western blot analysis.

The identification of pituitary antigens recognized by human antipituitary antibodies (APAs) is important in evaluating the pathophysiology of multiendocrine disorders linked to autoimmune factors. However, there is no convenient method for the quantitative analysis of circulating APAs. This study reports the development of an enzyme-linked immunosorbent assay (ELISA) for the detection of APAs. APAs were measured by ELISA and confirmed by Western blot analysis in sera from patients with endocrine disorders. APAs were detected frequently in patients with autoimmune thyroiditis, insulin-dependent diabetes mellitus (IDDM), or pituitary dwarfism. Circulating APAs were detected in 18% of patients with autoimmune thyroiditis. Confirmation by Western blot revealed positivity for APAs in the serum of 36% of patients with Hashimoto disease and in 29% of patients with Graves disease. Notably, 39% of patients with IDDM were also positive for APAs by ELISA. The identification of APAs by ELISA may be useful in evaluating autoimmune mechanisms involved in patients with multiendocrine disorders.

Adult↗

Oncocytic lipoadenoma of the submandibular gland.

We report a case of oncocytic lipoadenoma of the submandibular gland, previously unrecognized benign tumor of the salivary gland. The patient was a 66-year-old Japanese woman with a left submandibular mass, measuring 11 x 7.5 x 5 cm. Microscopically, the mass was completely surrounded by a thin fibrous connective tissue capsule, and was composed of an intimate admixture of mature fat cells and oncocytes. There have been no English reports of such a neoplasm in the salivary gland with the exception of one recent case report of lipoadenoma of the parotid gland without oncocytic features. We propose the diagnostic term "oncocytic lipoadenoma" for this benign tumor.

Adenoma↗

Mycosis fungoides with involvement of the oral mucosa.

Mycosis fungoides (MF) is a T-cell lymphoma that predominantly affects the skin. Involvement of the oral tissues in MF is rare. A case of MF with involvement of the maxillary gingiva and cervical lymph nodes is presented. Electron-beam radiation with 40 Gy and systemic chemotherapy with vincristine and interferon gamma produced almost complete remission of the oral lesion while the persistent pain was relieved.

Antineoplastic Agents, Phytogenic↗

Human parathyroid hormone does not influence human erythropoiesis in vitro.

BACKGROUND: Although renal anaemia is associated with secondary hyperparathyroidism, the relationship of both conditions remains obscure. Previously it was reported that high levels of bovine parathyroid hormone (PTH) did not inhibit in vitro human erythropoiesis, but whether human PTH inhibits in vitro human erythropoiesis has not been determined. METHOD: To clarify the direct effects of human biologically active N-terminal (1-34) PTH and intact (1-84) PTH on human haematopoietic progenitor growth, we investigated colony assays of human erythropoiesis and granulomonopoiesis. RESULTS: Neither N-terminal PTH (300 ng/ml) nor intact PTH (5000 pg/ml) inhibited haematopoietic progenitor growth. CONCLUSION: Our findings confirm that human PTH does not directly inhibit human erythropoiesis.

Animals↗

Oxidative stress and mitochondrial damage precedes gastric mucosal cell death induced by ethanol administration.

Although it has been speculated that active oxidants and mitochondrial membrane damages play roles in ethanol-induced gastric mucosal damages, its detail remains unknown. The present study was designed to investigate whether ethanol induces oxidative stress and mitochondrial permeability transition (MPT) before cell death of gastric mucosal cells. Rat gastric mucosal cells (RGM-1) were kept in serum-free Dulbecco's modified Eagle's medium before addition of various concentrations of ethanol. Nuclear morphological aftemations and membrane barrier dysfunction of RGM-1 cells were assessed by staining with Hoechst 33342 and propidium iodide, respectively. To assess the contribution of oxygen-derived free radicals and intracellular glutathione, scavenger of hydrogen peroxide and the hydroxyl radical, N,N-dimethylthiourea, glutathione precursor, N-acetyl-L-cysteine, and an inhibitor of alcohol dehydrogenase, 4-methylpyrazole were added before treatment with ethanol. To investigate MPT, calcein and tetramethylrhodamine methyl ester were loaded before addition of ethanol, and the changes of fluorescence intensity were monitored using a laser scanning confocal microscope. Ethanol (>5% v/v) dose-dependently increased the number of propidium iodide-positive cells, suggesting a diminished barrier function of cell membrane. After addition of ethanol, mitochondria were filled quickly with calcein indicating MPT, which was accompanied by mitochondrial depolarization, as shown by loss of tetramethylrodamine methyl ester before cell death. Ethanol-induced cell death was significantly attenuated by simultaneous incubation with either N,N-dimethylthiourea or N-acetyl-L-cysteine, suggesting the importance of intracellular redox states in inducing cellular damage, whereas such change was not attenuated by 4-methylpyrazole. Present results suggest that ethanol treatment induces intracellular oxidative stress and produces MPT and mitochondrial depolarization, which are preceding cell death in gastric mucosal cells. Intracellular antioxidants, such as glutathione, may have a significant protective action against ethanol in gastric mucosal cells.

Animals↗

Epstein-Barr virus-associated Hodgkin's disease in HTLV-I seropositive patients: a report of two cases.

Diagnosis of Hodgkin's disease (HD) is quite difficult in the patient with seropositivity for human T cell lymphotropic virus I (HTLV-I). Herein, two cases of Epstein-Barr virus (EBV)-associated HD, which occurred in males with seropositivity for anti-HTLV-I, are reported. One patient is alive and was diagnosed as having interfollicular HD with CD20+CD15-CD30-CD3-CD4-CD8-CD45RO-Read-Sternberg (R-S) cells. Positivity for EBV-encoded RNA 1 (EBER-1) and latent membrane protein 1 (LMP-1) was shown on follicular germinal center cells and R-S cells. In that case, neither T cell receptor (TCR) beta chain rearrangement nor integration of the HTLV-I provirus was demonstrated in the lymph nodes, although atyical lymphocytes (2%) were found in the peripheral blood. The other case pursued an aggressive clinical course and the patient was diagnosed as having an adult T cell leukemia/lymphoma (ATLL) because of the presence of anti-HTLV-I antibody, lymph node swelling, and the appearance of flower-like cells in the peripheral blood. However, an autopsy revealed no obvious ATLL cell infiltration in any of the organs examined. Multiple granulomatous lesions were found in the bone marrow, liver, kidneys, spleen, and lymph nodes. Reassessment of lymph node lesions in biopsies and granulomatous lesions in autopsy samples demonstrated that both lesions contained CD15+CD30+CD3-CD4-CD8-CD20-CD45RO-EBER-1+L MP-1+R-S cells, and they were considered to be a composite lymphoma of HD and ATLL. These two cases therefore suggest that EBV-associated HD can develop in patients with seropositivity for HTLV-I.

Antigens, CD↗

Gastric metastasis from breast cancer: a pitfall in gastric biopsy specimens.

A 49-year-old woman presented with abdominal discomfort and weight loss. Gastroduodenoscopy showed small polypoid lesions and biopsy specimens suggested primary adenocarcinoma with neuroendocrine differentiation. As the patient had a prior history of metachronous breast cancer, it was concluded that the case was metastatic carcinoma from the breast. The usefulness of a panel of selected immunohistochemical markers to determine the primary site of the breast in an appropriate clinical setting is greatly emphasized.

Adenocarcinoma↗

Oxyphilic cell variant of endometrioid adenocarcinoma.

A case of oxyphilic cell variant of endometrioid adenocarcinoma is presented. To the best of our knowledge, there have been only three such cases reported in the English literature. The patient was a 35-year-old Japanese female (gravida 0, para 0). She was slightly obese with profuse vaginal bleeding. Histological examination of the resected uterus revealed endometrioid adenocarcinoma with an exclusive oxyphilic cell component. There was no evidence of myometrial invasion nor lymph node metastases. Reported cases of oxyphilic cell variant of endometrioid adenocarcinoma, including the present case, were stages 0-1 and grades 1-2. Although further study is necessary to evaluate this variant, oxyphilic cell variant seems to be an early stage of adenocarcinoma and should be differentiated from eosinophilic metaplasia and other types of adenocarcinoma of the endometrium.

Adenocarcinoma↗

S-100 protein-positive dendritic cells in follicular lesions of the thyroid.

Little is known about the role of S-100 protein-positive dendritic cells in follicular lesions of the thyroid. In 36 cases of adenomatous goitre, 18 cases of follicular adenoma, and 7 cases of follicular carcinoma, we investigated the incidence and distribution of S-100 protein-positive dendritic cells using immunohistochemical staining. Four cases (10.5%) of adenomatous goitre, five cases (31.3%) of follicular adenoma, and 6 cases (85.7%) of follicular carcinoma contained S-100 protein-positive dendritic cells in the subcapsular area and/or the hyalinized stroma. Dendritic cells in the subcapsular area were observed only in lesions with thick capsules and not those with thin capsules. In most cases of follicular carcinoma, + + to + + + of the dendritic cells was seen together with a few lymphocytes and fibroblasts in the subcapsular areas. In contrast, cases of adenomatous goitre and follicular adenoma showed only a few dendritic cells without any inflammatory cells. Dendritic cells in follicular thyroid lesions may play some role in capsular formation or may be a secondary phenomenon due to capsular formation.

Adenocarcinoma, Follicular↗

Papillary squamous cell carcinoma of the uterine cervix: diagnostic pitfalls.

A case of papillary squamous cell carcinoma (PSCC) of the uterine cervix is reported. The patient was a 73-year-old Japanese woman with acute renal failure and bilateral hydronephrosis. A cauliflower-like mass was found in the uterine cervix. A uterine cervical biopsy specimen revealed PSCC in situ, while clinically it was an invasive carcinoma. Uterine cervical biopsy was performed a second time to confirm its stromal invasion. However, only small fragments were obtained because of heavy bleeding from the tumor and they showed PSCC in situ again. Following this, computed tomography of the pelvis revealed a 5 cm mass in the uterine cervix, invading the vagina and urinary bladder. Though deep-wedge biopsy, loop electrosurgical excision, or cone biopsy is recommended to evaluate PSCC, it may be impossible to perform any of these procedures because of bleeding such as that seen in our case. In these circumstances, good communication between pathologists and clinicians is important since lack of communication may cause PSCC to be microscopically misinterpreted as in situ carcinoma rather than invasive carcinoma.

Aged↗

Sarcomatoid renal cell carcinoma with chromophobe cell foci. Report of a case.

We report a case of sarcomatoid renal cell carcinoma with chromophobe cell foci. The patient was a 57-year-old Japanese woman with a renal mass measuring 12x8x8 cm in diameter. Histologically, the tumor was composed predominantly of sarcomatoid renal cell carcinoma with foci of chromophobe cell carcinoma. The patient died of multiple metastases 2 months after operation. To the best of our knowledge, there have been only two reports of the coexistence of sarcomatoid renal cell carcinoma and chromophobe renal cell carcinoma in the literature. Our case indicates that chromophobe cell carcinoma may be connected with sarcomatoid renal cell carcinoma. In such a case, the prognosis may be related to the latter component.

Adenocarcinoma↗

Encephalocele with an area mimicking giant cell fibroblastoma. Case report.

We report a unique case of encephalocele with an area mimicking giant cell fibroblastoma. A 4-month-old boy had been born with a parietal midline mass of the head, measuring 3x3x1.5 cm. Microscopically, it consisted of fibrous connective tissue and brain tissue. The fibrous tissue revealed spindle cells and multinucleated giant cells lining sinusoid-like spaces. This area was reminiscent of giant cell fibroblastoma. These cells were immunopositive for vimentin and negative for CD34. The giant cell fibroblastoma-like lesion in our case seems to be non-neoplastic and hamartomatous, and we think that the immunohistochemistry using CD34 is useful for differentiating the two lesions.

Antigens, CD34↗

Increased expression of an inducible isoform of nitric oxide synthase and the formation of peroxynitrite in colonic mucosa of patients with active ulcerative colitis.

BACKGROUND: Increased production of reactive metabolites of oxygen and nitrogen has been implicated in chronic inflammation of the gut. The object of this study was to examine the magnitude and location of nitric oxide synthase (NOS) activity and peroxynitrite formation in the colonic mucosa of patients with ulcerative colitis in relation to the degree of inflammation. SUBJECTS: Thirty three patients with active ulcerative colitis (17 with mild or moderate inflammation, 16 with severe inflammation). METHODS: Inducible NOS activity was determined in the colonic mucosa by measuring the conversion of L-arginine to citrulline in the absence of calcium. The localisation of NOS and nitrotyrosine immunoreactivity was assessed immunohistochemically using the labelled streptavidin biotin method. RESULTS: Inducible NOS activity increased in parallel with the degree of inflammation of the mucosa. Expression of inducible NOS was found not only in the lamina propria, but also in the surface of the epithelium. Peroxynitrite formation as assessed by nitrotyrosine staining was frequently observed in the lamina propria of actively inflamed mucosa. CONCLUSIONS: Nitric oxide and peroxynitrite formation may play an important role in causing irreversible cellular injury to the colonic mucosa in patients with active ulcerative colitis.

Acute Disease↗

Intraepithelial haemorrhage of the oesophagus: a terminal event in haematological disorders.

AIMS: To investigate the clinicopathological findings in cases with intraepithelial haemorrhage of the oesophagus (IHO). METHODS: Necropsy records and the histopathology findings in the oesophagus were reviewed for the period 1990 to 1995. Six cases (0.7%) of IHO were found among 919 necropsy cases. Clinical records of these patients and gross and microscopic slides were reviewed in detail. RESULTS: The ages of the IHO cases ranged from 42 to 82 years (average 68 years), with a male to female ratio of 1:2. All cases had underlying haematological disorders with thrombocytopenia, but disseminated intravascular coagulation was not evident in any case. Macroscopically, solitary (two cases) or multiple (four cases) haemorrhagic lesions ranging from 6 to 79 mm in size were identified within the distal oesophagus. Microscopically, there was no inflammatory infiltration, destruction of red blood cells, or submucosal scar formation. CONCLUSIONS: IHO seems to occur shortly before death as a terminal event in haematological disorders. Based on these observations, the term "terminal IHO" can be suggested for this type of oesophageal lesion.

Adult↗

Induction of endothelin-1 synthesis by IL-2 and its modulation of rat intestinal epithelial cell growth.

Endothelin (ET), a vasoconstrictive peptide, is known to have a variety of biological actions. Although ET is released by vascular endothelial cells, other cell populations also have been reported to synthesize and release ET. In this study, we examined whether ET is synthesized by intestinal epithelial cells and whether it affects induction of epithelial cell proliferation by interleukin-2 (IL-2). Subconfluent monolayers of intestinal epithelial cells (IEC-6 and IEC-18) were maintained in serum-free medium before addition of rat IL-2. Both IEC-6 and IEC-18 cells released ET-1 into the medium under unstimulated conditions, as determined by a sandwich ELISA. IL-2 significantly enhanced ET-1 release in a time-dependent manner. ET-3 was not detectable in the culture media of either cell line. Expression of ET-1 and ET-3 mRNA in epithelial cells was assessed by competitive PCR. Both cell lines were shown to express ET-1 mRNA, but no ET-3 mRNA was detected. IL-2 treatment enhanced ET-1 mRNA expression by both IEC-6 and IEC-18 cells. Both cell lines also expressed mRNA for ETA and ETB receptor subtypes. When cell proliferation was assessed, exogenous ET-1 induced a slight proliferative response in both types of cells that was consistent and significant at low ET-1 concentrations; cell growth was inhibited at a higher concentration (10(-7) M). IL-2 produced a significant proliferative response in both cell lines. However, the addition of ET-1 (10(-7) M) to culture media attenuated the IL-2-induced increase in cell proliferation. ETA-receptor antagonists significantly enhanced cellular proliferation, suggesting involvement of the ETA receptor in modulation of IL-2-induced intestinal epithelial cell growth.

Animals↗