Involvement of JC virus-infected mononuclear cells from the bone marrow and spleen in the pathogenesis of progressive multifocal leukoencephalopathy.
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Biomedical subjects
Publications and source records attributed to S Pittaluga.
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The role of a T gamma gene product in the immune response is not known. To investigate the participation of the T gamma gene in functional T cells, we estimated its variable (V gamma) gene diversity among mature polyclonal T cells and assayed for in vivo selection of rearranged V gamma genes during the immune response. In this study, we present evidence that functionally mature, normal human T cells have rearranged their T gamma genes but display a limited range of gene rearrangement choices. In contrast to clonal T cell neoplasms, an invariant array of seven T gamma gene rearrangements was found to be proportionately distributed within normal polyclonal T cell populations, as well as in benign polyclonal T cell proliferations incited by a wide variety of pathological conditions. Findings presented here indicate that the likelihood of rearrangement of each human V gamma gene may be fixed. Lack of selection of V gamma genes during the mature T cell immune response implies a limited role of any single V gamma gene at this stage of T cell development.
To investigate the relationship of the lymphoid hyperplasia of angioimmunoblastic lymphadenopathy with dysproteinemia (AILD) to supervening malignant lymphoma, we subjected DNA from lymph nodes and peripheral blood mononuclear cells from five AILD patients to Southern blot analysis to detect clonal rearrangements of immunoglobulin and T-cell receptor genes. Lymph nodes and peripheral blood from AILD patients were found to contain clones of lymphoid cells harboring either immunoglobulin or T-cell receptor gene rearrangements that, in some instances, regressed during the course of disease. A lymph node from one patient was involved by immunoblastic lymphoma and manifested an additional gene rearrangement pattern not seen in premalignant specimens from that patient. In contrast, DNA obtained from normal peripheral blood mononuclear cells and 11 examples of other forms of lymphoid hyperplasia showed no gene rearrangements. As a disorder of cellular immunoregulation in which lymphoid cells may escape normal growth controls, AILD provides a natural model to dissect stages of lymphomagenesis in man.
Acquisition of mature T cell function and the T cell antigen receptor repertoire occur in the thymus. In an effort to delineate the cascade of events leading to T cell maturation, we analyzed a series of clonal human precursor T cell neoplasms representing early, middle, and late stages of intrathymic differentiation. Rearrangements of the T cell receptor beta and gamma genes appear concurrently and are preceded by surface expression of the 3A1 (CD7) molecule. Subsequent transcription of the beta gene is coordinated with surface expression of T1 (CD5) and T11 (CD2), transcription of T3 delta mRNA, and the appearance of intracellular T3 (CD3) protein. As late events, T alpha gene transcripts appear and, finally, T3, the multichain complex linked to the T cell receptor, is presented on the cell surface. Findings reported here provide a model of the developmental orchestration of genes encoding antigen recognition in human T cells.
The phenotypes of early stages of T cell maturation are reflected by precursor T (lymphoblastic) neoplasms. In the present study, a series of such neoplasms was analyzed to reveal the developmental association of the expression of stage-related cell surface markers and T cell receptor gene rearrangement. Rearrangements of the T cell receptor beta-chain (T beta) gene were found in most, but not all, cases (88%) of T cell lymphoblastic neoplasms. T beta gene rearrangement preceded surface expression of the T cell receptor-linked molecular complex T3. Of all monoclonal anti-T cell antibodies tested, only antibody 3A1 was capable of reacting with neoplastic cells from all cases irrespective of the occurrence of T cell receptor gene rearrangements. In contrast, markers T1 and T11, normally expressed by mature T cells, were absent from the neoplastic cells in many cases (73% and 60% positive cases, respectively). Thus, antibody 3A1 is a valuable probe for the identification of T lymphoblastic neoplasms since its target antigen is consistently expressed and does not require prior T beta gene rearrangement. Furthermore, expression of 3A1 prior to T beta gene rearrangement suggests that it may be a cell surface protein that participates in the triggering of T cell receptor gene rearrangement and expression. It is concluded that precursor T cell neoplasms display an early T cell development hierarchy that, in sequence, consists of 3A1 expression, T beta gene rearrangements, and surface T3 expression.
A case of a cauda equina paraganglioma in a 13-year-old boy is described. A review of literature revealed six similar reported cases. All were intradural extramedullarly tumors located in the cauda equina-filum terminale region. In all, the presenting and dominant symptom was low back pain, while neurologic deficit was mild or absent. Excessive CSF protein levels appeared to be a characteristic feature of the disease. Histologically, the tumor displayed the typical "Zellballen" pattern, however mild nuclear pleomorphism and some mitotic figures were noted. As it is impossible to predict the biological behaviour of paragangliomas from the histologic appearance, complete surgical resection with close follow-up is indicated in such cases.
Earlier reports have suggested that low-dose ionizing irradiation might be involved in induction of intracranial meningiomas. One of the problems in evaluating irradiation-induced neoplasms is the belief that these tumors have no distinguishing features to indicate their etiology. In an attempt to identify such features in meningiomas following irradiation, a group of 42 post-irradiation meningiomas (PIM's) has been compared with a group of 84 non-PIM control meningiomas. These 42 PIM's included all the intracranial meningiomas diagnosed at the Hadassah University Hospital during the years 1952 to 1981 in individuals treated in childhood with low-dose x-ray therapy for tinea capitis. Although the individual PIM does not seem to differ from a "spontaneous" meningioma, this study indicates that PIM's as a group have distinct characteristics, namely, their location at the site of maximal irradiation, and features suggesting rapid growth and aggressive biological behavior. There was a significantly higher number of calvarial tumors (p less than 0.001), a high proportion of multiple meningiomas, a higher recurrence rate following apparent complete excision (p less than 0.02), and an increased number of histologically malignant meningiomas (p less than 0.01). The demonstration of features that distinguish PIM's from meningiomas of other etiology supports the suggestion that low-dose ionizing irradiation was involved in the pathogenesis of these tumors.
A fusiform longitudinal hemorrhagic necrosis of the spinal cord is described in a patient with spinal cord compression caused by metastases from an adenocarcinoma of the prostate. The lesion extended from the D3 down to L2 level with maximal involvement of the D7-D8 segments. The shape, location, and distribution of the lesion and its prominent hemorrhagic component corresponded to Jellinger's category of cylindrical liquefaction necrosis, probably due to venous obstruction. The multiple thrombi found in epidural veins supported such a pathogenic mechanism, which although extremely rare has been reported previously in five cases.
A morphometric analysis of the lobular components of the liver of normal male rats up to 6 months from portacaval anastomosis revealed that the mean volume of each hepatocyte decreased about 30-40% in normally fed rats and this was associated with a shrinkage of the lobular tissue. A 10% reduction of the total hepatocyte volume density in the lobule and a net increase in time of the fat storing cell volume density could be measured, whereas the intralobular collagen decreased. Within the hepatocytes a persistent significant increase of fat globules was observed; an increase in the first period, followed by a decrease of the lysosomal component. The Golgi complex tended to decrease in the first period, then exhibited a volume density even higher than in the controls. A small reduction of the rough endoplasmic reticulum and a conspicuous reduction of the smooth endoplasmic reticulum and, in fed animals, of the glycogen content were also observed. These alterations were persistent with periods of up to 6 months from the anastomosis and were present in all the functionally distinct lobular zones. From the ultrastructural point of view, apart from variations due to the quantitative changes described above, both lobular and hepatocytic components were identical to those of age matched controls at all times from the intervention. The ultrastructural damages described by others could not be observed.
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OBJECTIVES: Helicobacter pylori infection induces gastritis, which may evolve to carcinoma or lymphoma. Whether duration of infection and inflammation pattern determine the outcome of the neoplastic process is not known. The aim of this study was to investigate the features of the gastritis associated with neoplasia. METHODS: Gastritis found in association with carcinoma (100 cases) and lymphoma (45 cases) were graded using the Sydney system. RESULTS: In particular in the antrum, gastric carcinomas, in particular of the intestinal type, were associated with a chronic (94%, n = 34/36) atrophic (92%, n = 33/36) gastritis and intestinal metaplasia (81%, n = 29/36). In diffuse type carcinomas inflammation was either absent or mild. An active (64%, n = 16/25), chronic gastritis (100%, n = 25/25) with lymphoid hyperplasia (72%, n = 18/25) was found in marginal zone cell lymphoma. CONCLUSIONS: Our study shows that the (pre)atrophic phases of inflammation are associated with gastric carcinomas. In contrast the active phase of inflammation, characterized by severe activity as well as severe chronicity, is found next to marginal zone cell lymphoma.
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