Virchows Archiv. B, Cell pathology including molecular pathology最新文献

To elucidate the role of apoptosis and cell desquamation in the repair phase of acute tubular necrosis, morphological findings after 60 min ischaemia were investigated in rats. A morphometric analysis of the cell proliferation and of the epithelial cellularity of reconstructing tubules was performed. The kinetics of apoptosis and cell desquamation were also examined. Ischaemia and reperfusion injury resulted in widespread necrosis of tubules at day 1. Subsequently, a regenerative epithelial hyperplasia took place in the early stage. The most marked increase in cellularity in the damaged tubules was on day 6, when the tubules became lined by hyperplastic epithelial cells with papillary clusters. The number of papillary clusters decrease up to day 8, and during this period many desquamated cells from the clusters were observed in the tubular lumen. In the later stage, hyperplastic epithelial cells were reduced to their original cellularity and during this period the number of apoptotic cells obviously increased, while the damaged tubules were reconstructed. We conclude that epithelial overproduction occurs in the early phase after tubular necrosis, and excess hyperplastic epithelial cells regress during the repair process by cell desquamation and apoptosis, both of which are essential for the recovery of the original tubular structure.

Spontaneously diabetic BB/Wor rats received either a syngeneic fetal pancreas transplant or adult islets. In the former, 4-8 fetal pancreases were transplanted, and in the latter, 3-5000 islets. Transplantation was performed by transferring a blood clot containing the pancreases or islets to the renal subcapsular space. Insulin therapy was undertaken postoperatively, except in one experiment with adult islets. Of the fetal pancreas transplanted BB rats, 52% became normoglycaemic, and 21% remained so throughout an observation period of 10 months. Nephrectomy caused a prompt return of diabetes. The histological appearance of the grafts transplanted to the diabetic animals closely resembled that of grafts transplanted to normal rats in a parallel series. For comparison a group of BB rats received a syngeneic transplant of isolated adult islets from WF rats or BBW rats. Following adult islet transplantation, 5 out of 6 animals became hyperglycaemic after a median of 20.5 days when no insulin was given post-transplantation. Four out of 5 animals became hyperglycaemic after a median of 23 days when supportive insulin therapy was administered after the transplantation. The results indicate that recurrent diabetes is not inevitable following syngeneic fetal pancreas transplantation to spontaneously diabetic BB rats. Recurrent diabetes was only occasionally associated with mononuclear cell infiltration. Transplanted tissue was well-preserved and vascularized; mega-islets were a constant finding.

Smooth muscle differentiation has been analysed in human myometrium and leiomyoma by Western blotting with antibodies to smooth muscle specific proteins. No differences in the expression of h-caldesmon, metavinculin, desmin, alpha-smooth muscle actin and calponin were observed. The technique of two-dimensional gel electrophoresis was used, therefore, to further analyse differences between normal smooth muscle cells and their neoplastic counterparts. By comparing the protein patterns of normal myometrium and leiomyoma, it was possible to identify a protein with a molecular weight of approximately 27 kD that is selectively expressed in normal uterine smooth muscle cells. This protein proved to be a low molecular weight variant of calponin, a smooth muscle specific protein of as yet unknown function. Its immediate downregulation in tissue culture of normal myometrium points to a possible role in the process of dedifferentiation.

Sequential changes in the expression of two glucose transporter isoforms (GLUT1, GLUT2), and in the activities of hexokinase, pyruvate kinase and malic enzyme during the development of rat renal basophilic cell tumors were studied using histochemical techniques. Early basophilic cell tubules are similar to proximal convoluted tubules (PCT) in their overall histochemical pattern, particularly in the expression of glucose transporters, suggesting that basophilic cell tubules and tumors derived from them arise from PCT. In comparison with PCT, basophilic cell tubules show slightly increased activities of all the enzymes studied. In basophilic cell tumors, markedly elevated hexokinase and pyruvate kinase activities are accompanied by a considerable reduction in the expression of GLUT2. GLUT1 expression is not found in basophilic cell tubules or PCT. Small basophilic cell tumors also do not express GLUT1, but GLUT1 is regularly expressed in several cell layers surrounding necrotic areas within large basophilic cell tumors. Our results indicate that increased glycolytic activity and reduced GLUT2 expression take place during the development of renal basophilic cell tumors.

The alterations appearing in trigeminal mesencephalic primary sensory neurons during ageing have been analyzed by electron microscopy in the Wistar-Louvain rat. Two phases have been distinguished, similar to those observed in dorsal root ganglion neurons. Up to 24 months, the mesencephalic trigeminal neurons progressively accumulate lipofuscins, while filamentous inclusions start to appear around 24 months of age. Hirano bodies and paired helical filament-like structures have been identified in animals aged 24 months or more. This time-course parallels the one observed previously in dorsal root ganglion neurons, indicating that the blood-brain barrier does not seem to influence the ageing of mesencephalic trigeminal neurons. The relationship between the paired helical filament-like inclusions and Hirano bodies, as well as similar structures already described by other authors, is discussed.

The virus-host interactions between Japanese encephalitis (JE) virus and mouse brain neurons were analyzed by electron microscopy. JE virus replicated exclusively in the rough endoplasmic reticulum (RER) of neurons. In the early phase of infection, the perikaryon of infected neurons had relatively normal-looking lamellar RER whose cisternae showed focal dilations containing progeny virions and characteristic endoplasmic reticulum (ER) vesicles. The reticular RER, consisted of rows of ribosomes surrounding irregular-shaped, membrane-unbounded cisternae and resembled that observed in JE-virus-infected PC12 cells, were also seen adjacent to the lamellar RER. The appearance of the reticular RER indicated that RER morphogenesis occurred in infected neurons in association with the viral replication. The fine network of Golgi apparatus was extensively obliterated by fragmentation and dissolution of the Golgi membranes and their replacement by the electron-lucent material. As the infection progressed, the lamellar RER was increasingly replaced by the hypertrophic RER which had diffusely dilated cisternae containing multiple progeny virions and ER vesicles. The Golgi apparatus, at this stage, was seen as coarse, localized Golgi complexes near the hypertrophic RER. In the later phase of infection, RER of infected neurons showed a degenerative change, with the cystically dilated cisternae being filled with ER vesicles and virions. Small, localized Golgi complexes frequently showed vesiculation, vacuolation, and dispersion. The present study, therefore, indicated that during the viral replication the normal lamellar RER which synthesized neuronal secretory and membrane proteins was replaced by the hypertrophic RER which synthesized the viral proteins. The hypertrophic RER eventually degenerated into cystic RER whose cisternae were filled with viral products. The constant degenerative change which occurred in the Golgi apparatus during the viral replication suggested that some of the viral proteins transported from RER to the Golgi apparatus were harmful to the Golgi apparatus and that increasing damage to the Golgi apparatus during the viral replication played the principal role in the pathogenesis of JE-virus-infected neurons in the central nervous system.

Histogenetic features of lung tumours were studied in Syrian hamsters that had been induced with 6.8 mg N-nitrosomethyl-n-heptylamine/animal by gavage once a week for 35 weeks. At intervals from experimental week 2 until week 46, pulmonary tissues from hamsters were examined by light and electron microscopy. This report describes early hyperplastic lesions associated with terminal bronchioles and the progression of these lesions to bronchioloalveolar tumours. Using immunohistochemical and ultrastructural colloidal gold labelling techniques, hamster Clara cell antigen was found to be localized in Clara cell granules and smooth endoplasmic reticulum of normal cells, in dysplastic Clara cells migrating through basement membrane defects or from the open end of terminal bronchioles, and in hyperplastic peribronchiolar cell foci. The latter progressed to bronchioloalveolar tumours growing out along alveolar basement membranes in a characteristic lace-like, lepidic pattern. Tumours were composed of secretory (Clara), ciliated, mucous, and undifferentiated cells, as well as trapped, non-neoplastic alveolar type II cells. Hyperplastic neuroendocrine cell foci lining airways were immunoreactive for chromogranin, but these cells did not participate in the pre-neoplastic or neoplastic process. It is suggested that bronchioloalveolar carcinomas in hamsters are derived from bronchiolar secretory (Clara) cells growing along alveolar walls, differentiating into other bronchiolar cell types and entrapping resident alveolar type II cells. Due to the migratory capacity of Clara cells, it is also possible for tumours composed of bronchiolar cells to develop at the lung periphery.

Obstruction and increased secretory activity are considered to be important aetiological factors of salivary microlithiasis, which may itself be an aetiological factor of sialadenitis. However, there is a lack of substantial evidence for the importance of obstruction, and investigations on increased secretory activity used pathological doses of pharmacological agents. Therefore further investigation of these factors is essential. Feline parotid, submandibular and sublingual salivary glands, in which microliths occur normally as in man, were examined after ductal ligation to produce obstruction, electrical stimulation of the glandular nerves to produce increased secretory activity, or both. Microliths were detected in: 0 out of 38 untreated, 1 out of 55 ligated, 2 out of 17 stimulated and 2 out of 17 stimulated ligated submandibular glands; 6 out of 29 untreated, 7 out of 46 ligated, 3 out of 12 stimulated and 4 out of 14 stimulated ligated sublingual glands; and no parotid glands. The chi 2 test confirmed that the experimental procedures did not produce an increased occurrence of microliths. Microliths were detected in parenchymal cells, intercellularly in atrophic parenchyma, intraluminally, interstitially and in macrophages. The present investigation indicates that obstruction and increased secretory activity are not important aetiological factors of salivary microlithiasis.

The reliability of histopathological diagnosis in bone marrow specimens from patients with chronic myeloproliferative disorders (CMPD) was evaluated by correlating the histological findings with molecular genetic and cytogenetic analyses of the Ph1-translocation. A rearrangement of m-bcr was detected only in patients (28/30) diagnosed histologically as chronic myeloid leukemia (CML). This finding was supported by the presence of a Ph1-chromosome in 24/26 patients with CML examined. All the patients with other types of CMPD, including polycythemia vera (PV), primary thrombocythemia (PTH) and chronic megakaryocytic-granulocytic myelosis (CMGM), as well as those with unclassifiable CMPD (CMPD.UC) were Ph1-negative (n = 38). The histopathological discrimination of CML from Ph1-negative varieties of CMPD was also reliable for patients with myelofibrosis complicating CML, CMGM and CMPD.UC. The results demonstrate that bone marrow histopathology allows a reliable diagnosis of CML. This is in contrast with hematological data such as high platelet counts which show considerable overlapping in the various forms of CMPD.

The nm23 gene, which encodes nucleoside diphosphate (NDP) kinase, is proposed as a metastatic suppressor gene. Loss of heterozygosity (LOH), and the expression of the nm23 gene were examined on matched sets of primary tumors and lymph node as well as distant metastases from colorectal carcinomas. Three (15%) of the 20 informative specimens examined showed LOH for the nm23 locus. nm23 was expressed in all the carcinomas as well as in nonneoplastic colonic mucosa at the mRNA and protein levels. Most of the carcinomas expressed the nm23 transcript at higher levels than the corresponding nonneoplastic colonic mucosa. By Western blotting, the level of nm23 protein expression in the tumors showed an inverse correlation with the tumor stage. Furthermore, distant metastatic tumors in the liver and lung showed reduced nm23 immunoreactivity in comparison with their primary tumor, although nm23 immunoreactivity was the same in the primary tumors and in local lymph node metastases. These results suggest that decreased nm23 expression may be associated with distant metastatic spread.