Osteoblastic proliferation in bone biopsies from patients with end-stage chronic renal failure.

Osteoblasts have traditionally been considered to be terminally differentiated cells and therefore unable to divide. Data in recent years, however, indicate that cellular differentiation does not usually preclude preservation of proliferative ability and that most differentiated cells are able to divide under adequate stimuli. The aim of this study was to assess whether cubic osteoblasts undergo proliferation during the formation phase of the remodeling cycle under a stimulus that increased bone turnover. For that purpose, the osteoblastic proliferation index (OPI) was analyzed by DNA image cytometry in transiliac bone biopsies from 33 patients with chronic renal failure (23 men, 10 women; mean age 50.4 +/- 15.1 years) who have been classified into low (n = 13), normal (n = 15), and high (n = 15) bone turnover according to activation frequency (Ac.f). OPI was significantly higher (p < 0.002) in the high bone turnover group (13.90 +/- 4.72%) compared with the low (2.38 +/- 4.13%) and normal turnover groups (2.84 +/- 4.04%). There was a positive correlation between OPI and the following histomorphometric parameters: bone formation rate, surface referent (r = 0.76, p = 0.00001), activation frequency (r = 0.73, p = 0.00001), mineral apposition rate (r = 0.73, p = 0.00001), bone formation rate, volume referent (r = 0.71, p = 0.00001), and mineralizing surface (r = 0.62, p = 0.0001). This study shows that a rise in bone turnover is associated with a marked increase of bone-forming cell proliferation in patients with end-stage chronic renal failure. From this finding, it may be concluded that cubic osteoblasts do not behave as "terminally differentiated" cells in vivo, because a high proportion of them are still able to divide.

DNA amplification in glial cells of progressive multifocal leukoencephalopathy: an image analysis study.

JC virus (JCV), the agent of progressive multifocal leukoencephalopathy (PML), has been shown by both immunohistochemistry and flow cytometry to be associated with p53 protein stabilization. Since stabilization/inactivation of p53 is associated with the development of genomic instability, abnormal cell DNA contents are to be expected in JCV-infected cells of PML. This work explores that possibility by image analysis evaluation of DNA content in PML-infected oligodendrocytes and bizarre astrocytes. Brain paraffin sections of PML lesions from five adult male patients with the acquired immune deficiency syndrome (AIDS) were treated with the Feulgen technique to obtain a stochiometric staining of DNA and analyzed with a microscope image processor. Inclusion-bearing oligodendrocytes exhibited near tetraploid DNA indices in each of the five cases, whereas atypical astrocytes were in the hypertetraploid range in all cases and were polyploid in four instances. This evidence of DNA amplification in PML glial cells is congruent with the functional abolition of p53 protein in association with JCV infection and lends further support to the role of p53 as a keeper of diploid status and guardian of genomic stability.

Renal cell carcinoma with syncytial giant cell component.

We report a case of clear cell renal cell carcinoma in which a prominent multinucleated giant cell component was intermingled with clear, granular, and spindle cells. Histological, ultrastructural, cytometric, and cytogenetic features of giant cells were similar to those of mononucleated cells in the tumor, and therefore they were not from stromal or osteoclast derivation. These giant cells had homogeneous, finely granular, abundant cytoplasm, often with scalloped cell borders, and contained from 5 to more than 50 nuclei, all of them very similar in size and shape, with prominent central nucleoli. Occasionally, surrounding inflammatory cells were also engulfed in the cytoplasm. This syncytial appearance was more similar to that of some giant cell carcinomas from the lung than to the pleomorphic giant cells often encountered in high grade renal cell tumors. Although the patient is alive and free of disease 6 years after diagnosis, a longer follow-up will be required to assess the potential prognostic influence of this peculiar histological appearance.