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Biomedical subjects

Ryohei Katoh

Publications and source records attributed to Ryohei Katoh.

At least 19 recordsLinked to original sources

Expression of aquaporin 3 (AQP3) in normal and neoplastic lung tissues.

Aquaporin 3 (AQP3) acts as the membrane channel of water and other small solutes and plays a major role in fluid homeostasis. To investigate the expression of AQP3 in normal and neoplastic lung tissues, we studied a series of 149 lung carcinoma tissues and 2 cell lines by immunohistochemistry, Western blotting, and reverse transcriptase-polymerase chain reaction. In normal lung tissues, immunohistochemical expression of AQP3 was demonstrated in bronchial basal cells, alveolar type II cells, bronchiolar epithelial cells, and secretory cells of submucosal glands. In lung carcinomas, AQP3 expression was observed in 59 (70.2%) of 84 adenocarcinomas. Squamous cell carcinoma and large cell carcinoma had rather low positive ratios (35.8% and 13.4%, respectively). No AQP3 expression was demonstrated in small cell carcinoma, pleomorphic carcinoma, or metastatic colon adenocarcinoma. In adenocarcinomas, AQP3 was detected in all tumors of bronchioloalveolar subtype. Papillary subtype also showed a higher positive ratio of AQP3 compared with that in acinar and solid with mucin subtypes. In addition, AQP3 expression was related to tumor differentiation and clinical stage in adenocarcinomas. Western blotting and reverse transcriptase-polymerase chain reaction analyses confirmed the expression of AQP3 protein and messenger RNA in cell lines and tissues of lung adenocarcinoma. We conclude that AQP3 is widely expressed in the normal respiratory tract and can play an important role in the maintenance of water homeostasis. In addition, lung carcinomas, especially adenocarcinomas, can produce AQP3, possibly in connection with their functional and/or biological nature, although the detailed mechanism of AQP3 expression in lung carcinomas remains to be clarified.

Adenocarcinoma↗

Immunohistochemical study of NG2 chondroitin sulfate proteoglycan expression in the small and large intestines.

The intestinal subepithelial myofibroblasts (ISEMFs) are located in the lamina propria under the epithelial cells. ISEMFs are thought to have an important role in protecting and maintaining the integrity of the epithelial cell layer and also in the process of wound healing. In this study, we report that the membrane-bound proteoglycan NG2 is abundantly distributed in the ISEMF layer of the mouse and human intestines. NG2 immunostaining in this layer is distributed with similar intensity from the crypt to villi. NG2 is also immunolocalized along the membranes of smooth muscle cells in the intestinal muscle layer. However, skeletal and cardiac muscles are not immunostained for NG2, demonstrating selective expression of the proteoglycan by smooth muscle cells. Using electron microscopy, NG2 immunoreactivity was strongly observed along the cell membranes of ISEMF, with weak diffusion into the neighboring matrix, indicative of the presence of some "shed" NG2. This first report of NG2 proteoglycan expression by ISEMF provides insights into the nature of the interaction of these cells with extracellular matrix and/or intestinal epithelial cells.

Animals↗

p16INK4a overexpression independent of human papillomavirus infection in lobular endocervical glandular hyperplasia.

A high rate of human papillomavirus (HPV) infection has been reported in cervical cancer and precancerous lesions. Many studies also have shown that p16INK4a overexpression is of diagnostic value for high-risk HPV-related cervical cancer and precursors. Lobular endocervical glandular hyperplasia (LEGH) is a rare lesion of the uterine cervix. There is one report about HPV infection and few studies on p16INK4a expression in LEGH. Therefore, we 1) detected HPV infection and examined p16INK4a expression and 2) observed the relationship between HPV and p16INK4a overexpression in LEGH. The immunohistochemical expression of p16INK4a was studied in 24 cases of LEGH. HPV DNA was also evaluated in these cases using a polymerase chain reaction technique. Strong (++) p16INK4a immunoreactivity was observed in 10 (41.7%) of the 24 LEGH cases; a moderate (+) pattern was observed in 9 (37.5%) cases; a weak (+) pattern was observed in 2 (8.3%) cases; and the remaining 3 (12.5%) cases showed negative expression. Overall, p16INK4a overexpression was seen in 87.5% of the cases (21/24). HPV DNA was not detected in any of the 24 LEGH cases. These results suggest that p16INK4a overexpression is independent of HPV infection in LEGH.

Adult↗

RET gene rearrangements (RET/PTC1 and RET/PTC3) in papillary thyroid carcinomas from an iodine-rich country (Japan).

BACKGROUND: The frequency of RET rearrangements (RET/PTC) in papillary thyroid carcinomas varies significantly according to geographic area, with the greatest incidence reported in the Belarus region, which is iodine-deficient and was contaminated severely after the Chernobyl reactor accident, and with the lowest incidence in iodine-rich, nonirradiated Japan. The authors investigated the prevalence of RET/PTC in a large number of thyroid tumors from Japanese patients. METHODS: Fresh and paraffin embedded tumor tissues from 215 Japanese patients were examined for RET rearrangements (RET/PTC1 and RET/PTC3) by means of reverse transcriptase-polymerase chain reaction analysis, with primers flanking the chimeric region, followed by direct-sequence analysis. RESULTS: RET/PTC was found only in papillary carcinomas and was not observed in other histologic types of thyroid tumors. The overall frequency of RET/PTC in papillary carcinomas was 28.4%, with a greater frequency in younger patients, including 41.9% of younger patients age < 20 years, 27.6% of patients age 20-40 years, and 24.8% of patients age > 40 years. Among the patients in these 3 age groups, the prevalence rate of RET/PTC1 was similar, but RET/PTC3 was observed most frequently among patients age < 20 years. When the tumors were grouped further according to histologic subtypes, the prevalence of RET/PTC3 was greater in solid/solid-follicular papillary carcinomas than in classic papillary carcinomas. CONCLUSIONS: The results indicated that RET/PTC may be useful as a specific molecular marker for papillary thyroid carcinomas. Furthermore, its incidence in such tumors was not low in Japanese patients, and it seemed to be associated with patient age. Therefore, the current results raise questions regarding the belief that the frequency of RET/PTC differs geographically and is especially low in Japan.

Adult↗

Stromal elastosis in papillary thyroid carcinomas.

Stromal elastosis, defined as dense aggregations of elastic fibers, is found in some neoplastic tissues especially in malignant tumors of the breast and lung. Although also found in thyroid tissue, stromal elastosis in thyroid neoplasms have received little attention. To clarify the histopathological significance of stromal elastosis in the thyroid, we examined neoplastic (n = 223) and hyperplastic (n = 82) thyroid tissues in conjunction with cancer tissues (n = 193) of various other organs. Stromal elastosis was observed as deposits of pale homogeneous material in hematoxylin and eosin stain, and distinctively highlighted by elastic-van Gieson's stain. On immunohistochemical examination, elastin and tropoelastin were confirmed in these deposits. Stromal elastosis was found in 66% of papillary thyroid carcinomas (PTCs), although it was not identified in other histological types of thyroid neoplasms. In PTCs, deposits of elastic fibers varied in size and shape, and were more frequently distributed in the periphery of the tumor tissue. The histological subtypes of PTC varied in prevalence of elastosis with the follicular variant's (9%) prevalence being significantly lower than that of the classical type (72%). The frequency of stromal elastosis in PTCs was very similar to the frequencies in breast and lung adenocarcinomas, and higher than the frequencies in carcinomas of other organs. In conclusion, our results suggest that stromal elastosis is a characteristic histological finding of PTCs, presumably associated with their growth pattern and/or histological architecture. It is, therefore, reasonable to propose that stromal elastosis is an ancillary feature in the histopathological diagnosis of PTCs.

Carcinoma, Papillary↗

Mucinous carcinoma (poorly differentiated carcinoma with extensive extracellular mucin deposition) of the thyroid: a case report with immunohistochemical studies.

We report on a case of mucinous carcinoma of the thyroid in an 82-year-old Japanese woman. The 3 x 2 x 2-cm thyroid tumor located in the patient's right lateral lobe was soft and yellowish gray on the cut section. Microscopically, the tumor was composed entirely of strands or solid clusters accompanied by extensive extracellular mucin. Extracellular mucin was positive with Alcian blue stain and negative with periodic acid-Schiff stain. Immunohistochemically, the tumor cells were positive for thyroglobulin, thyroid-specific transcription factor 1, and low-molecular-weight cytokeratin but negative for carcinoembryonic antigen, calcitonin, and high-molecular-weight cytokeratin. The MIB-1 labeling index was rather high (11%), and immunoexpression of p53 was detectable in the nuclei of carcinoma cells. From these findings, we classified the present tumor as a mucinous carcinoma of the thyroid (poorly differentiated thyroid carcinoma producing massive extracellular mucin). The patient died of multiple metastases 4 years after the initial operation.

Adenocarcinoma, Mucinous↗

Endocervical adenocarcinomas associated with lobular endocervical glandular hyperplasia: a report of four cases with histochemical and immunohistochemical analyses.

We report on four cases of endocervical adenocarcinoma associated with lobular endocervical glandular hyperplasia using histochemical and immunohistochemical analyses. The patients ranged in age from 59 to 67 years (mean 62 years). Chief complaints were watery vaginal discharge in two cases, genital bleeding in one and no subjective symptoms in one. Cytological examinations of the cervical smears revealed adenocarcinoma cells and benign-looking glandular cells with intracytoplasmic golden-yellow mucin in all cases. Radical hysterectomy was performed in three patients, and simple total hysterectomy was performed in one. From surgical specimens, three tumors were diagnosed as mucinous adenocarcinoma and one was adenocarcinoma in situ. All adenocarcinomas were located proximally on the cervix, and did not involve the transformation zone. Adjacent to carcinoma tissues in the cervix, lobular endocervical glandular hyperplasia was detected. The cells of lobular endocervical glandular hyperplasia were dominantly positive with neutral mucin, and immunohistochemistry revealed that these cells had prominent pyloric gland mucin (HIK1083). Focal immunopositivity for pyloric mucin was also observed in three adenocarcinomas. Either CEA or p53 were immunopositive in all adenocarcinomas and negative in the tissues of lobular endocervical glandular hyperplasia. Histopathological features of the present cases suggest that some endocervical adenocarcinomas may originate from lobular endocervical glandular hyperplasia.

Adenocarcinoma↗

Absence of human papillomavirus infection in minimal deviation adenocarcinoma and lobular endocervical glandular hyperplasia.

The human papillomavirus (HPV) is basically always detected in squamous cell carcinoma of the cervix and its precursors; a high incidence of HPV also has been reported in adenocarcinoma and adenocarcinoma in situ of the uterine cervix. Lobular endocervical glandular hyperplasia (LEGH) was first described by Nucci in 1999. It is difficult to differentiate minimal deviation adenocarcinoma (MDA) from LEGH preoperatively or postoperatively by clinical and pathologic features. The relationships between HPV and MDA or LEGH have not been studied well because of the rare incidence of the two diseases. To our knowledge, the HPV status in LEGH has not been reported. This study was designed to investigate HPV infection in MDA and LEGH, using the polymerase chain reaction (PCR) technique. Tumor tissue lesions were microdissected and the detection of HPV and its typing were analyzed by PCR-based assay. As the control, HPV DNA was detected in all cases of squamous cell carcinoma and three of five cases of adenocarcinoma. However, no HPV DNA was detected in any of the 10 cases of LEGH or in the 3 cases of MDA. These results suggest that MDA and LEGH are probably not related to HPV infection.

Adenocarcinoma↗

Autopsy case of microscopic polyangiitis with crescentic glomerulonephritis and necrotizing pancreatitis.

Herein is reported the case of an 84-year-old woman who initially manifested rapidly progressive glomerulonephritis following a urinary tract infection. Laboratory findings showed a high titer of myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA). Treatment with high-dose i.v. steroids resulted in clinical recovery and an undetectable MPO-ANCA titer. Two months later the patient was readmitted in a state of severe shock. Laboratory examination showed the deterioration of renal function, leukocytosis, and coagulation abnormalities consistent with disseminated intravascular coagulation (DIC). The patient died 12 days later. The post-mortem examination revealed necrotizing pancreatitis due to acute-stage vasculitis typified by fibrinoid necrosis of the arterioles and venules, and crescentic glomerulonephritis with healed-stage vasculitis. In the lungs, capillaritis with diffuse alveolar hemorrhage was not evident, but arteriolitis and phlebitis were occasionally seen. This case represents an unusual complication of necrotizing pancreatitis in the setting of microscopic polyangiitis. Thus, it is important to consider reactivation independent of the titer of ANCA in the course of the disease.

Aged↗

Application of cryotechniques with freeze-substitution for the immunohistochemical demonstration of intranuclear pCREB and chromosome territory.

Intranuclear localization of signal molecules and chromosome territories has become more attractive in relation to postgenomic analyses of cellular functions. Cryotechniques and freeze-substitution (CrT-FS) have been generally used for electron microscopic observation to obtain better ultrastructure and immunoreactivity. To investigate benefits of applying the CrT-FS method to immunostaining of intranuclear signal molecules and FISH for chromosome territories, we performed an immunohistochemical study of phosphorylated cAMP-responsive element binding protein (pCREB) in mouse cerebellar tissues and a FISH study of chromosome 18 territory in human thyroid tissues using various cryotechniques. The immunoreactivity of pCREB was more clearly detected without antigen retrieval treatment on sections prepared by the CrT-FS method than those prepared by the conventional dehydration method. In the FISH study, more definite probe labeling of the chromosome territory could be obtained on paraffin sections by the CrT-FS method without microwave treatment, although such labeling was not clear even with microwave treatment on sections prepared by the routine dehydration method. The CrT-FS preserved relatively native morphology by preventing shrinkage of nuclei, and produced better immunoreactivity. Because the reduction of routine pretreatments in the present study might reveal more native morphology, the CrT-FS method would be a useful technique for intranuclear immunostaining and FISH.

Animals↗

Immunolocalization of protein 4.1B/DAL-1 during neoplastic transformation of mouse and human intestinal epithelium.

Recently, we have reported that the protein 4.1B immunolocalization occurred only in matured columnar epithelial cells of normal rat intestines. This finding suggested that protein 4.1B expression could be examined for a possible change during neoplastic transformation of the intestinal mucosa. In the present study, we first present the distribution of mouse protein 4.1B in normal intestinal epithelial cells and tumor cells using the adenomatous polyposis coli (Apc) mutant mouse model. A low level of protein 4.1B expression coincided with the phenotypic transition to carcinoma. To examine the protein 4.1B expression in human intestinal mucosa, we used another antibody against an isoform of the human protein 4.1B, DAL-1 (differentially expressed adenocarcinoma of the lung). Human DAL-1 was also expressed in matured epithelial cells in human colons, with a definite expression gradient along the crypt axis. In human colorectal cancer cells, however, DAL-1 expression was not detected. These results suggest that mouse protein 4.1B and human DAL-1 might have a striking analogy of functions, which may be integrally involved in epithelial proliferation. We propose that loss of protein 4.1B/DAL-1 expression might be a marker of intestinal tumors, indicative of a tumor suppressor function in the intestinal mucosa.

Animals↗

Human dendritic cell lysosome-associated membrane protein expressed in lung type II pneumocytes.

Human dendritic cell LAMP (hDC-LAMP) is a unique member of the lysosome-associated membrane protein (LAMP) family with a tissue distribution initially described as restricted to major histocompatibility class II (MHC II) compartments of activated DC before the translocation of MHC II to the cell surface [Immunity 9 (1998) 325]. In this report, we show that hDC-LAMP is also expressed by lung type II pneumocytes, another cell type with constitutive expression of MHC II. A recombinant hDC-LAMP protein and a monospecific anti-hDC-LAMP polyclonal antibody were prepared. The antibody reacted specifically with hDC-LAMP sequences of hDC-LAMP protein expressed in transfected cells and with a 54 kDa protein of normal human lung tissue with properties corresponding to those of transgene expressed hDC-LAMP. Immunohistochemical analysis of hDC-LAMP in human lung showed its presence in alveolar type II epithelial cells (type II pneumocytes) as well as in cells in the interfollicular area of bronchus-associated lymph nodes, where interdigitating DCs are concentrated, and with lesser staining of alveolar macrophages. The native protein contained approximately 16% carbohydrates, most of which are sialyl N-linked oligosaccharides, with an acidic isoelectric point (pI 4.8). The restricted localization of this protein to lung type II pneumocytes and DCs is in contrast to hLAMP-1, which was present in many cell types of the lung and lymph node. Type II pneumocytes are known to express MHC II and the abundant expression of hDC-LAMP in these cells as well as in DCs suggests its possible relationship to specific MHC II related function(s) of DC and type II pneumocytes.

Antigens, CD↗

Mixed papillary adenocarcinoma and transitional cell carcinoma of the uterine cervix.

A mixed papillary adenocarcinoma and transitional cell carcinoma (MAcTcc) was discovered in the uterine cervix of a 38-year-old woman. A condylomatous papillary lesion was found in the uterine cervix during a colposcopic study and histopathological examination showed that the tumor was composed of two different neoplastic subtypes. One was an adenocarcinoma (AC) component showing papillary and tubular structure with endocervical and intestinal differentiation; the other was a transitional cell carcinoma (TCC) component showing papillary excrescence mimicking papillary TCC of urothelial origin. To characterize the tumor, an immunohistochemical study of cytokeratins (CK) was performed. The AC component showed immunoreactivities similar to conventional adenocarcinomas: positive immunoreactivity of low-molecular-weight cytokeratins 7, 8 and 19, and negative immunoreactivity of CK20 and high-molecular-weight cytokeratin (34betaE12). The lower epithelial layer of the TCC component showed different immunoreactivity, but the superficial epithelial layer had similar immunohistochemical findings to the AC component. These findings indicate that the TCC component had the cellular character of AC rather than that of TCC or squamous cell carcinomas. This is thought to be the first report of a MAcTcc of the uterine cervix.

Adenocarcinoma, Papillary↗

[Hormone production and secretion in thyroid tumors].

Thyroid epithelial cells can be classified into 2 types according to embryonic origin, those of foregut endoderm (follicular cells) and those of neuroectodermal deviation (C cells) origin. The production of TG, T4, and T3 is frequently evident with the immunoperoxidase methods is nontoxic thyroid tumors derived from follicular cells. In contrast, medullary thyroid carcinoma originated from thyroid C cells produces and secretes calcitonin. Thyroid transcription factor-1 (TTF-1) regulates the expression of all hormones produced in thyroid. In recent years, evidence has been accumulating for the existence of a tumor group with traits of both follicular and medullary carcinoma, designated as mixed follicular and medullary carcinoma.

Calcitonin↗

Morphological abstraction of thyroid tumor cell nuclei using morphometry with factor analysis.

Various morphonuclear studies by digital image analysis have successfully been applied to quantify the nuclear morphology, including chromatin distribution pattern, in cytology of various organs; however, the majority of past reports have not shown correlation between the quantitative data by digital image analysis and cytological findings in practical diagnosis. In this report, we present the usefulness of morphological abstraction to combine the objective data and subjective observation in cytological diagnosis. Randomly selected, 100 cells in each Papanicolaou-stained ABC smear samples of 39 benign and malignant thyroid tumor cases were studied. Gray-level image data provided seven parameters for nuclear size, four parameters for nuclear shape, and 16 parameters showing the nuclear chromatin patterns from high-dimensional texture analysis of using co-occurrence and run-length matrices. To statistically abstract nuclear morphology, factor analysis was used. Factor analysis classified morphological nuclear characters as abstraction parameter into five abstract parameters composed of nuclear size, shape, heterogeneity, and contrast and homogeneity of chromatin pattern. The nuclei of papillary carcinoma showed larger size, more irregular shape, and higher contrast of chromatin pattern than those of the benign group. The follicular carcinomas have larger nucleus in each cell and more monotonous chromatin pattern among cells in each case than those of the benign group. Morphological abstraction by morphometry with factor analysis may provide a practical approach to the detection of the underlying characteristics of nuclear morphology in aspiration biopsy cytology.

Cell Nucleus↗

Angiogenesis in endocrine glands: special reference to the expression of vascular endothelial growth factor.

Recent studies have shown that several angiogenic growth factors are produced and secreted by normal endocrine cells and are increased in pathological states of endocrine glands, including inflammation, hyperplasia, and neoplasia. Expression of corresponding receptors on epithelial cells and/or endothelial cells enables these angiogenic factors to influence growth and function of the endocrine tissues by auto- or paracrine mechanisms. Some of the angiogenic factors are also considered to be involved in angiogenesis, which is a critical process in tumor formation and progression. Vascular endothelial growth factor (VEGF) is regarded as one of most important angiogenic factors with specific effects on endothelial cell growth and vascular permeability, and is isolated from a variety of normal and neoplastic endocrine cells. In this article, recent studies on angiogenic factors, especially on expression of VEGF, are reviewed in the field of endocrine systems.

Adrenal Glands↗

Expression of human pendrin in diseased thyroids.

We examined pendrin expression in various diseased thyroid tissues by immunohistochemistry (IHC) using antiserum raised against human pendrin and by real-time quantitative RT-PCR. In normal thyroids the antiserum reacted with the apical membrane of follicular cells and its immunoreactivity was faint. In Graves' thyroids, the IHC expression of pendrin appeared in a pattern similar to that of normal thyroids but it was more extensive and stronger, especially in areas showing marked proliferation of follicular cells. The immunoreactivities of pendrin in nodular goiters varied from case to case. In follicular adenomas, pendrin was localized in the follicle-forming parts of the tumor but was negative in trabecular parts. Pendrin was negative in all follicular carcinomas, papillary carcinomas, and in one case of medullary carcinoma. In quantitive mRNA analysis, the relative values of pendrin mRNA were significantly low in papillary carcinoma (p<0.01), whereas the values in other diseased thyroids were not significantly different from those in normal thyroids. These results suggest that pendrin may play a role in thyroid hormone production as the apical porter of chloride/iodide and investigation of pendrin leads to a better understanding of functional aspects of the iodine transportation system in thyroid diseases.

Carrier Proteins↗