Precocious expression of T cell functional response genes in vivo in primitive thymocytes before T lineage commitment

The genes encoding effector molecules of mature T cells, IL-2, perforin and IL-4, were found to be expressed in vivo in the most primitive subsets of thymocytes of adult mice. These subsets have previously been identified by their cell surface markers and by their expression of other T lineage-associated genes. While IL-2, perforin and IL-4 are expressed in distinct patterns, all three are expressed before the induction of RAG-1 and pre-TCR alpha mRNA expression, and are confined to subsets of cells that apparently have not yet undergone commitment to the T lineage. Thus, expression of T cell response genes appears to be one of the earliest markers of lymphocyte differentiation. Activation events marked by CD69 induction occur in these early cell types, but the response gene expression by these cells is separable from CD69 expression. IL-2 and perforin are induced again much later in thymocyte development, during TCR-dependent repertoire selection. At those stages, IL-2 protein and RNA levels per cell are higher, but the fraction of cells expressing IL-2 appears to be much lower than in the most immature stages. In addition, a striking feature of the immature populations is the robust IL-2 expression by presumptive immature NK cells. These findings are discussed in terms of the developmental origins of lineage specificity in T cell response gene regulation.      

Etiology of AIDS-related Kaposi's sarcoma and lymphoma

Kaposi's sarcoma (KS) and non-Hodgkin's lymphomas (NHL) are common consequences of HIV infection. These tumours appear to be precipitated by herpesviruses. Epstein-Barr virus (EBV) is implicated as a cause of up to 50% of systemic NHLs and up to 100% of central nervous system lymphomas in patients with AIDS. KS may be a consequence of the newly identified gamma-herpesvirus KSHV (KS-associated herpesvirus or HHV-8). This herpesvirus is found in all KS biopsies from different epidemiologic forms of this disease. KSHV is also implicated in the pathogenesis of a rare form of B cell lymphoma called body-cavity based lymphoma or primary effusion lymphoma (PEL).     

Rechtsverhältnisse am menschlichen Körper unter besonderer Berücksichtigung einer Kommerzialisierung der Organ- und Gewebetransplantation

Zusammenfassung Der Beitrag befasst sich mit Rechtsverhältnissen am menschlichen Körper unter Berücksichtigung einer möglichen Kommerzialisierung. Medizin und Wissenschaft sind auf Organe und Gewebe zur adäquaten Versorgung der Bevölkerung, aber auch zur Zukunftssicherung des Forschungsstandortes Deutschland angewiesen. Rückläufige Spenderzahlen haben zu einer Organ- und Gewebeknappheit in Deutschland geführt und die Diskussion um eine Kommerzialisierung von Organ- und Gewebetransplantationen wieder entbrennen lassen. Den geäußerten Kommerzialisierungstendenzen stehen strafsanktionierte Regelungen im Transplantationsgesetz (TPG) und Resolutionen der WHO bzw. die Bioethik-Konvention des Europarates entgegen, die Handel mit menschlichen Organen und Geweben ablehnen bzw. verbieten. Nach der Rechtsprechung des Bundesverfassungsgerichts kam dem Gesetzgeber im Anwendungsbereich des TPG unter Berücksichtigung der medizinischen Möglichkeiten, der ethischen Anforderungen und der gesellschaftlichen Vorstellungen ein weiter Beurteilungs- und Gestaltungsspielraum zu. Trotz der Regelungen im TPG verschärft sich der Organ- und Gewebemangel in Deutschland. Deshalb erfährt die gesetzgeberische Gestaltung vermehrt Kritik, die sich u. a. auf die strafrechtliche Ausgestaltung des TPG und die ausgebliebene Förderung der Spendebereitschaft durch die erweiterte Zustimmungslösung bezieht.     

Computed Tomographic Findings in 50 Cases of Gall Bladder Carcinoma

Background

A retrospective assessment of contrast enhanced computed tomography (CECT) scan findings in histopathologically proven cases of carcinoma of the gallbladder (GB) was performed to review its role in diagnosis, staging and assessment of surgical resectability.

Methods

All the patients had been subjected to a standardised abdominal helical computed tomography scan. Orally administered iodinated contrast was used for opacification of bowel and dynamic intravenous injection of non-ionic iodinated contrast for studying the lesional enhancement and vascular structures.

Results

The presence of focal or diffuse mass lesions in the gallbladder fossa, infiltration of a liver and second part of duodenum were the most reliable diagnostic features in carcinoma gallbladder. Regional spread was better delineated on CT scan as compared with ultrasonography.

Conclusion

CT scan is an effective method for evaluating, characterizing and detecting the spread of GB carcinomas.Key Words: Gall Bladder, Carcinoma, Computed Tomography     

Successful transplantation of Friend virus-induced preleukemia into stem cell-deficient fetal mice

The leukemias induced by the Friend polycythemia virus and other leukemogenic retroviruses have previously not been transplantable until weeks or months after virus inoculation. Because tumor-specific immune mechanisms persist in both irradiated and nude mice, it has not been possible to determine if this result is due to rejection of cells already immortalized by retrovirus infection, or reflects an inherent limitation in the proliferative capacity and malignancy of these "preleukemic" cells. To clarify these issues, we have transplanted virus-infected bone marrow into mouse fetuses that are immunologically immature and thus incapable of graft rejection. We report here that within days of virus inoculation, transplantable cells capable of disease progression in certain fetal hosts can be detected with this technique. These results demonstrate that cells with the capacity for extensive leukemic proliferation arise very early in Friend virus- induced disease. However, successful transplantation was seen only in genetically anemic recipients (Wx/Wv), which are deficient in hematopoietic stem cells, and not in their normal littermates. Thus, in accord with recent in vitro observations, this in vivo data suggests that normal hematopoietic cells, independent of immune mechanisms, can suppress the malignant progression of transformed cells.     

Direct demonstration that autologous bone marrow transplantation for solid tumors can return a multiplicity of tumorigenic cells

Patients with solid tumors are increasingly being treated by autologous bone marrow transplantation (BMT). Although response rates appear to be increased, disease recurrence is the commonest cause of treatment failure. Whether relapse is entirely due to residual disease in the patient or arises also from infiltrating malignant cells contained in the autologous marrow transplant has not been resolved. If the latter explanation is correct, then purging would be required as part of the transplantation procedure. We used retrovirally mediated transfer of the neomycin-resistance gene to mark BM harvested from eight patients with neuroblastoma in clinical remission. The marked marrow cells were subsequently reinfused as part of an autologous BMT. At relapse, we sought the marker gene in malignant cell populations. Three patients have relapsed, and in each the marker gene was detected by phenotypic and genetic analyses of resurgent malignant cells at medullary and extramedullary sites. Analysis of neuroblast DNA for discrete marker gene integration sites suggested that at least 200 malignant cells, each capable of tumor formation, were introduced with the autologous marrow transplant and contributed to relapse. Thus, autologous BMTs administered to patients with this solid tumor may contain a multiplicity of malignant cells that subsequently contribute to relapse. The marker-gene technique we describe should permit evaluation of the mechanisms of relapse and the efficacy of purging in patients receiving autologous marrow transplantation for other solid tumors that infiltrate the marrow.