Biomedical subjects
Publications and source records attributed to K Kadota.
A diastereocontrolled route to conduritols A-F has been developed starting from a common chiral building block containing an oxabicyclo[3.2.1]octane framework.
We have systematically characterized gene expression patterns in 49 adult and embryonic mouse tissues by using cDNA microarrays with 18,816 mouse cDNAs. Cluster analysis defined sets of genes that were expressed ubiquitously or in similar groups of tissues such as digestive organs and muscle. Clustering of expression profiles was observed in embryonic brain, postnatal cerebellum, and adult olfactory bulb, reflecting similarities in neurogenesis and remodeling. Finally, clustering genes coding for known enzymes into 78 metabolic pathways revealed a surprising coordination of expression within each pathway among different tissues. On the other hand, a more detailed examination of glycolysis revealed tissue-specific differences in profiles of key regulatory enzymes. Thus, by surveying global gene expression by using microarrays with a large number of elements, we provide insights into the commonality and diversity of pathways responsible for the development and maintenance of the mammalian body plan.
The RIKEN Mouse Gene Encyclopaedia Project, a systematic approach to determining the full coding potential of the mouse genome, involves collection and sequencing of full-length complementary DNAs and physical mapping of the corresponding genes to the mouse genome. We organized an international functional annotation meeting (FANTOM) to annotate the first 21,076 cDNAs to be analysed in this project. Here we describe the first RIKEN clone collection, which is one of the largest described for any organism. Analysis of these cDNAs extends known gene families and identifies new ones.
cDNA microarray technology is useful for systematically analyzing the expression profiles of thousands of genes at once. Although many useful results inferred by using this technology and a hierarchical clustering method for statistical analysis have been confirmed using other methods, there are still questions about the reproducibility of the data. We have therefore developed a data processing method that very efficiently extracts reproducible data from the result of duplicate experiments. It is designed to automatically filter the raw results obtained from cDNA microarray image-analysis software. We optimize the threshold value for filtering the data by using the product of N and R, where N is the ratio of the number of spots that passed the filtering vs. the total number of spots, and R is the correlation coefficient for results obtained in the duplicate experiments. Using this method to process mouse tissue expression profile data that contain 1,881,600 points of analysis, we obtained clustered results more reasonable than those obtained using previously reported filtering methods.
A 2-year-old Holstein cow developed multiple cutaneous masses, up to 10 cm in diameter, over the neck and trunk. The animal also had neoplastic lesions in internal organs, and epitheliotropism was observed not only in the skin but also in the conjunctiva, mammary glands, trachea, abomasum, small intestine, gall bladder, uterus and urinary bladder. Moreover, the neoplastic cells showed preferential homing to T-zones of lymphatic tissues. Because the lymphoma cells were positive for CD3 but not CD79a, and a few were CD2- or WC1-positive, this lymphoma was thought to be of gammadelta T-cell origin. Helicobacter -like organisms, found in the abomasum and small intestine, were considered to be associated with the severe neoplastic involvement of these organs, on the basis of the intense immunolabelling for major histocompatibility complex class II in the epithelial cells, and the presence of increased numbers of apparently normal intraepithelial T lymphocytes.
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OBJECTIVE: To describe a case of nocardial nasal granuloma in a Holstein heifer. CLINICAL FEATURES: The heifer showed laboured respiration and occasional coughing with granulomatous excrescences on the bilateral nasal mucosa, and a marked leucocytosis with eosinophilia. NECROPSY: Severe granulomatous inflammation with eosinophils, epithelioid cells, giant cells and Nocardia sp obstructed both nasal passages completely. CONCLUSION: This lesion resulted from chronic infection with Nocardia sp and is distinct from other forms of bovine nasal granuloma, also called atopic rhinitis or chronic granular rhinitis, which we propose should be classified as bovine allergic granular rhinitis. The most appropriate name for the present disease is bovine nasal eosinophilic granuloma.
In a 5-year-old Holstein cow, a neoplasm composed of a large intramuscular mass and multiple metastases in the lungs and lymph nodes was diagnosed as a pleomorphic rhabdomyosarcoma. This neoplasm was characterized by marked variation in tumor cell size and giant cells with single bizarre nuclei. Although the presence of cross striations and myoglobin could be confirmed, expression of alpha-smooth muscle actin (SMA) was also recognized in a few cells. Neoplastic cells showing intense staining for desmin, vimentin and proliferating cell nuclear antigen irrespective of their size differed from those in an embryonal rhabdomyosarcoma that exhibited a wide spectrum of differentiation, reminiscent of normal skeletal myogenesis. The cellular pleomorphism and SMA expression seemed to be characteristic of deviation from normal muscle cells or satellite cells in adult muscle.
Infection with Pneumocystis carinii was demonstrated immunohistochemically in the lungs of pigs 15 to 75 days of age from a herd with epidemic pneumonia due to the organism. The distribution of the organism was centered on the airways, and extended progressively with age from the alveolar ducts to the alveoli. In a retrospective immunohistochemical study of 245 newborn to adult pigs which were necropsied between 1988 and 1995, P carinii infection was found in 87 pigs (35.5 per cent) aged between 17 days to seven months. In the pigs aged between one and three months the infection rate was 63.1 per cent. Pigs from herds in which suckler and weaner pigs shared the same air space were more heavily infected than those from the herds in which they were reared separately. There were no regional or seasonal variations in the level of infection, and the infection was not associated with any single disease.
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To disclose the mechanism of cellular injury following porcine circovirus (PCV) infection, 12 pigs were examined by the terminal deoxynucleotidyl transferase-mediated dUTP-nick end labeling (TUNEL) method and immunohistochemistry. Histologically, the lymphoid tissues were characterized by marked apoptosis of lymphocytes, lymphocyte depletion, and macrophages and giant cells containing numerous inclusion bodies with or without apoptotic bodies. Immunohistochemically, there were many lysozyme-positive macrophages in the lymphoid follicles, while the number of CD79a-positive B lymphocytes was scanty. Apoptotic cells, which were proved to be TUNEL positive, revealed CD79a positivity. Although detectable mainly in the cytoplasm of macrophages, PCV antigens were found also in the nuclei of macrophages and apoptotic lymphocytes. Ultrastructurally, the presence of PCV virions was confirmed in apoptotic bodies phagocytosed by macrophages. These findings suggested that lymphocyte depletion with apoptotic death of B lymphocytes was caused by PCV, and that some of the inclusion bodies were phagolysosomes derived from the apoptosis. Thus, PCV may trigger the development of wasting disease syndrome by producing an immunocompromised state in pigs.
Malignant histiocytosis was diagnosed in 4 cows. In all cases the tumor tissues were composed of cytologically atypical histiocytes with evidence of erythrophagocytosis. The tumor in case 1 appeared highly anaplastic with marked nuclear pleomorphism, and had areas of spindle cell differentiation, but had no relation to malignant fibrous histiocytoma. The neoplastic tissue in case 2, characterized by cohesive growth of tumor cells, was distinguishable from anaplastic carcinoma cells by cytokeratin immunostaining. There were many hemosiderin-laden neoplastic cells suggestive of high phagocytic activity in a lymph node of case 3. The neoplastic cells in case 4, frequently multinucleated, were less atypical than in the other cases. All cases expressed histiocyte-associated markers (lysozyme and HAM56), and were negative for cytokeratin, S100, and T- and B-cell lineage-specific markers (CD3 and CD79a). The most frequent HAM56 immunoreactivity was detected in case 4, and the giant, multinucleated forms, reminiscent of epithelioid cell differentiation. seemed not to indicate cytological pleomorphism as a result of neoplastic transformation.
A melanotic neurofibroma in a steer was investigated histologically, immunohistochemically and ultrastructurally. A very large tumor mass was located in the region of the head and right cheek. The tumor tissue consisted of an admixture of cells resembling Schwann cells and spindle-shaped cells, and they frequently contained melanin granules. Neoplastic Schwann cells were positive for S100 protein, with variation in intensity of staining, but most spindled cells were S100 negative. The tumor cells displayed ultrastructural features similar to those of Schwann cells or perineurial cells. The presence of melanosomes in varying stages of melanization in both cell types suggests that they have a common origin. This is a tumor of neural crest origin showing schwannian and perineurial differentiation, with ectopic production of melanin granules.
An acute myeloblastic leukemia was found in a 3.5-year-old Holstein cow. The neoplasm was characterized by massive tumor growths, and there were multiple tumor nodules in the dermis or subcutis and a large tumor mass in the mediastinum. This tumor showed negative reactivity for CD3, CD79a, major histocompatibility complex class II and myeloid/histiocyte antigen. Ultrastructural features such as dispersed cytoplasmic granules and poorly developed organelles were compatible with those of early promyelocytes.
An epizootiological survey with histopathological methods was conducted for porcine circovirus in 220 diseased pigs (1-200 days old) in 49 farms from 1985 to 1999. Histopathological lesions containing PCV antigen were detected mainly in the lymphoid tissues from 42 of 189 diseased pigs (22.2%) in 4 of 45 farms (8.9%) from 1990 to 1999. The rate of positive pigs gradually increased from 1997 onward and PCV infection was found in 50% of diseased pigs in 1999. Histopathologically, the lesions in the lymphoid tissues (including lymph nodes, Peyer's patches, tonsil and spleen) were highly correlated with the presence of numerous spherical basophilic intracytoplasmic inclusion bodies with PCV antigen, and consisted of lymphocellular depletion and infiltration of macrophages. Although most affected cells showed cytoplasmic reactivity for PCV, intranuclear antigen was also seen in the lymphocytes, macrophages and ileal epithelial cells. Ultrastructurally, macrophages and giant cells contained electron-dense, round to ovoid lysosomal bodies, in which there were concentric circle or paracrystalline arrays of small nonenveloped icosahedral viral particles, approximately 15-17 nm in diameter. Other consistent infectious agents were present in 90.5% of cases, and porcine reproductive and respiratory syndrome virus infection was in 52.4% of the cases with PCV. The histopathological findings suggested that PCV induced systemic immunosuppression in the infected pigs and made them more susceptible to infection of the organisms. Because of the presence of PCV antigens in the intestinal epithelium, feces may play a significant role in dissemination of PCV.
An intrathoracic sarcoma from a 7-month-old female pig was studied by light and electron microscopy and immunohistochemistry. The tumor tissue of varied cell density consisted chiefly of spindle-shaped cells, some of which grew around blood vessels in a concentric fashion. Many tumor cells were positive for alpha smooth muscle actin and not for desmin, though some cells were reactive for both antigens. A majority of tumor cells had ultrastructural features characteristic of myofibroblasts, but a few cells resembled vascular smooth muscle cells in the synthetic state. This neoplasm may have arisen from vascular smooth muscle with features indicating a transition to myofibroblasts.
Seven adult free-ranging sika deer (Cervus nippon yesoensis) were examined by histology, immunohistochemistry and electron microscopy for intestinal spirochetal infection. Histologically epithelial and goblet cell hyperplasia and edema of the lamina propria mucosa with macrophage and lymphocyte infiltration were observed in the cecum and colon in 6 of the 7 deer. Numerous argyrophilic spirochetes were present in the crypts and some had invaded epithelial and goblet cells and caused degeneration. Immunohistochemically the organisms stained positively with polyclonal antisera against Brachyspira (Serpulina) hyodysenteriae and B. pilosicoli. Ultrastructurally they were 6-14 microm long, 0.2-0.3 microm wide and had 4-6 coils and 13 axial filaments per cell; such features were closely similar to those in the Brachyspira species. These results showed that the spirochetes were capable of inducing enteritis in deer and this intestinal spirochete infection might already be prevalent among wild sika deer in Japan. There is a possibility that this spirochetal colitis is a new syndrome in sika deer and that the same and/or similar spirochetes have infected ruminants, including sika deer and cattle.