To clarify its biological nature, 10 samples of goblet cell-type adenocarcinoma of the lung were collected and compared with 10 other pulmonary mucin-producing adenocarcinomas with respect to immunohistochemical features and the presence of Ki-ras gene mutation in codons 12 and 13. Goblet cell-type adenocarcinomas lacked immunoreactivity for surfactant apoprotein and S-100 protein-positive Langerhans cells, which was in marked contrast to other mucin-producing adenocarcinomas. In addition, the mucin gene products, MUC-1 and MUC-2 glycoproteins were immunohistochemically stained. The results showed that MUC-1 glycoprotein is frequently expressed by mucin-producing adenocarcinomas except the goblet cell-type. Ki-ras gene mutation was detected in 12 of 20 (60%) mucin-producing adenocarcinomas. These mutations were exclusively found in codon 12 and G to A transitions were the most frequent type of alteration in the Ki-ras gene. In goblet cell-type adenocarcinomas, the frequency of Ki-ras gene mutation was 80% consisting of G to A transitions and G to T transversions in six and two tumors, respectively. Therefore, goblet cell-type adenocarcinomas differed from other mucin-producing adenocarcinomas in terms of immunohistochemical and molecular biological features, suggesting that goblet cell-type adenocarcinomas are distinctly different from other subtypes of adenocarcinomas.
Age-related changes in the olfactory system were examined in 22 dogs ranging in age from 10 to 19 years old. Atrophic changes with degeneration were observed in the olfactory epithelium of dogs older than 14 years; the changes were prominent in the dogs over the age of 17 years. Immunohistochemistry using an anti-carnosine antibody, which is a marker for the olfactory cells, demonstrated a decrease in the number of olfactory cells. Electron microscopy also showed a decrease in the number of cilia of olfactory cells and microvilli of supporting cells. Atrophic changes with the features of regeneration were rarely observed in the aged animals. Lipofuscin-like granules in the olfactory epithelium became prominent with age. These age-related changes were similar to those reported in the olfactory epithelium of man and rats. Dystrophic neurites were not detected by a modified Bielschowsky stain or by neurofilament, synaptophysin and tau immunohistochemistry in the olfactory mucosa. There was no beta-amyloid- and ubiquitin-immunostaining in the olfactory mucosa. Senile brain changes, including cerebrovascular amyloidosis, age-related astrocytic gliosis and ubiquitin deposits were found in the olfactory bulb, although neurofibrillary tangles and senile plaques were not detected either by a modified Bielschowsky stain or by beta-amyloid immunohistochemistry. These results indicate that dog may be a useful animal model to study the age-related changes in the olfactory system in man.
To elucidate the relationship between the clinical features and pathologic findings of primary pulmonary lymphoma, we reviewed 24 patients with this disease. The pulmonary lymphomas were divided into four groups: (1) B-cell lymphoma composed of small to medium-sized lymphoid cells (19 cases); (2) B-cell lymphoma composed of large lymphoid cells (three cases); (3) T-cell lymphoma (one case); (4) malignant lymphoma of lymphomatoid granulomatosis (LYG) type (one case). Radiographs of the first group revealed a predominance of infiltration associated with ill-defined tumor margins upon gross pathology, corresponding histologically to lymphangitic spread. Air bronchogram and pleural tail or abutment were additional radiographic features. Characteristics of the second group were a nodule or mass evident on radiographs and well-circumscribed tumor margins upon gross pathology. Lack of air bronchogram was an another radiographic feature in this group. Seventeen patients in these two groups underwent complete resection of the tumors and survived without recurrence, whereas four received chemotherapy after biopsy and survived with disease. These results indicate that primary pulmonary B-cell lymphoma is a low-grade malignancy and that complete resection is the only therapy which leads to cure. In a single patient with T-cell lymphoma, the radiographic and pathologic features of the tumor were indistinguishable from those in the first group, but the patient had an unfavorable prognosis. We consider that, from a prognostic viewpoint, it is important to determine the T- or B-immunophenotype of the tumor cells for diagnosis of primary pulmonary lymphoma. The only patient in this series with pulmonary lymphoma of LYG type showed distinctive clinicopathologic findings. We consider that this uncommon disease should be separated from other types of primary pulmonary lymphoma.
A 13-year-old male Shetland Sheepdog with progressive exophthalmos had a neoplastic mass in the ocular adnexa. Histologically, this neoplasm was composed of duct-forming epithelial cells with decapitation secretion. Tumor cells invaded the globe through the tunica conjunctiva and replaced the vitreous body. The cornea, iris, ciliary body, and retina were extensively destroyed. Both the epithelial and spindle-shaped myoepithelial cells showed nuclear atypia and mitotic activity in the globe. The primary tumor was diagnosed as adenocarcinoma, probably originating from apocrine sweat glands of the eyelid, and the infiltrating intraocular neoplasm was diagnosed as a malignant mixed tumor.
To elucidate the structure and control of expression of the porcine FSH-beta subunit gene, two genomic clones were isolated and the entire gene structure was determined to the extent of 10 kb, consisting of 6 kb of the 5'-flanking region and 4 kb of the transcriptional unit. The porcine FSH-beta gene consisted of three exons the same as the human and bovine genes, but the positions of both splicing sites of porcine intron-1 were unique. It is known that the synthesis of FSH is regulated by gonadal steroids, gonadotrophin-releasing hormone (GnRH) and inhibin. However, the consensus steroid-responsive element was unexpectedly absent in the 5'-flanking region of 6 kb. On the other hand, the potential binding sites for activator protein-1 (AP1) and AP2, which might be stimulated by the GnRH-protein kinase C cascade, were present at seven and five positions respectively. An imperfect cyclic AMP-responsive element was also present. Southern blot analyses, using the cDNA and genomic fragments as probes, gave smear patterns suggesting the presence of repetitive sequences in the porcine FSH-beta gene. A survey of homology with the repetitive sequences revealed that short interspersed repeated sequences (SINES)-type non-viral retroposons were present with about 250 bp length repeats twice in the 5'-flanking region and once each in intron-1 and the 3'-flanking region. Other SINES-like sequences were also found in intron-1, exon-2 and exon-3. In comparison with the 5'-flanking sequences of the porcine alpha and LH-beta genes, there were no significantly conserved regions, implying a lack of common modulation of the three subunit genes.
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