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Biomedical subjects

D T Purtilo

Publications and source records attributed to D T Purtilo.

At least 19 recordsLinked to original sources
PubMed1992

Early activation of the proto-oncogene c-fgr during Epstein-Barr virus immortalization.

In an attempt to clarify the chronological relationships between Epstein-Barr virus (EBV) infection, B cell immortalization and c-fgr activation, we evaluated for the presence of EBV-determined nuclear antigen (EBNA), cellular DNA synthesis and expression of c-fgr-specific RNA following infection of human peripheral blood lymphocytes with B95-8 EBV. High expression of c-fgr was observed prior to EBNA detection and cellular DNA synthesis in EBV-infected cells. These results suggest that activation of c-fgr is an essential event during the early phase of EBV immortalization.

Antigens, Viral↗
PubMed1992

Cellular proliferation and genetic events involved in the genesis of Burkitt lymphoma (BL) in immune compromised patients.

A mathematical model simulating lymphomagenesis based on the two-hit theory of carcinogenesis is presented by contrasting the biologic variables responsible for a high risk of developing Burkitt lymphoma (BL) in three immunosuppressed groups with that of nonendemic BL. In this model, the pro-B lymphocyte is considered to be the target for BL-specific translocations such as t(8;14). With repeated mitosis, the target cell pool expands in the high-risk individual, and, thereby, the opportunities for a spontaneous translocation to arise are increased. The chromosomal translocation endows the target cell with survival advantages, and, hence, lymphoma develops. Modeling results demonstrate that this increased cell proliferation is sufficient in accounting entirely for the increase in tumor prevalence. Preventing enhanced cellular proliferation by obviating immune deficiency and treating patients with agents that restore immunity or have antiviral and antiproliferative properties prior to conversion from polyclonal B-cell proliferation to monoclonal malignancy could obviate the development of BL.

B-Lymphocytes↗
PubMed1992

X-linked lymphoproliferative disease: prenatal detection of an unaffected histocompatible male.

Chorionic Villous Biopsy (CVS) for diagnosis of XLP was undertaken at 10 weeks gestation in an obligate carrier. The fetus was found to be male by cytogenetic analysis. XLP (Xq25-q26) is closely linked to the RFLP markers DXS10, DXS37 and DXS42, but only DXS10 (distal to XLP) was informative for prenatal diagnosis in this family. RFLP analysis using this marker gave a 7% risk that the fetus was affected, based on the known recombination frequency between DXS10 and XLP. Further investigation was then undertaken to obtain a rapid and more accurate diagnosis using the three highly polymorphic PCR based markers. These were the AC repeat markers DXS424 (XL5A) and DXS425 (XL90A3) and the tetramer repeat marker within HPRT. DX425 is approximately 10 cM proximal to DXS10 and HPRT but is not known with certainty to map proximal or distal to XLP. DXS424 is proximal to DXS10 and HPRT and was inferred to be proximal to XLP on the basis of map distance from HPRT estimated by linkage analysis of data from CEPH pedigrees. This was confirmed by a recombinant in the XLP family between DXS424 and DXS425, placing DXS424 proximal to XLP. Diagnosis by linkage using DXS424 and DXS425, at least one of which is proximal to XLP, and distal markers DXS10 and HPRT, increased the accuracy of diagnosis using flanking marker analysis to greater than 99% that the fetus was unaffected. HLA DR typing of the CVS showed that the fetus was DR identical to a male sibling with XLP. HLA compatibility was confirmed at delivery by full HLA typing and MLC.(ABSTRACT TRUNCATED AT 250 WORDS)

Child, Preschool↗
PubMed1992

Report on the X-linked lymphoproliferative disease in an Australian family.

X-linked lymphoproliferative disease is characterized by immune deficiency, particularly to the Epstein-Barr virus and by a tendency to develop fatal infectious mononucleosis, acquired hypogammaglobulinaemia or malignant lymphoma. This disorder has been diagnosed in three boys, two brothers and a maternally related cousin, residing in Australia. The proband presented at 6 years of age with fulminating infectious mononucleosis. His 9 year old male cousin had developed an ileal Burkitt lymphoma one year earlier. Immunological and molecular genetic evidence is presented to support our view that his younger sibling is also affected with this condition. DNA linkage studies using probes to DXS10 and DXS37 provide confirmatory evidence for the diagnosis in the proband's brother and information on carrier status in female family members.

Agammaglobulinemia↗
PubMed1992

Epstein-Barr virus-associated lymphoproliferative disorders.

Herein we have provided a panorama of the clinical, histopathologic, and molecular biologic mechanisms of EBV-induced LPD particularly in immunosuppressed individuals. A listing of EBV-related diseases is shown in Table 4. We have stressed the frequent need to use multiple diagnostic methods for detecting EBV genome, particularly in immunodeficient patients who may fail to mount antibody responses to EBV. Given that we now recognize some of the immunocompromised patient populations at high risk for EBV-induced LPD, and have developed techniques for detecting EBV genome and early LPD, we may eventually prevent the occurrence of some of these life-threatening diseases. For example, we have learned to recognize and distinguish hepatic allograft rejection from EBV-induced LPD in hepatic biopsies (154). A periportal and sinusoidal infiltrate of small and large lymphoid cells, immunoblasts, and plasma cells, alert us to stain frozen liver sections for EBNA. Finding EBV guides the clinicians to reducing immunosuppression which then allows the restoration of immunosurveillance against the EBV-infected B cells. Whether an EBV vaccine can be successful in immunosuppressed individuals remains to be seen. As for other vaccines, many logistical problems prevail, such as the early occurrence of EBV infection during infancy in regions where BL is endemic. Surely, with the menacing threat that approximately 10% of patients with AIDS will develop NHL, new anti-viral therapy against EBV and the causative agent of AIDS and HIV, will be developed. The pathologist and virologist play essential roles in the recognition of EBV infection by performing clinical laboratory determinations. The characteristic histopathologic features of EBV-induced LPD are now recognized and when confirmed with molecular hybridization and immunofluorescent techniques will provide a solid diagnostic approach and, thus, a foundation for developing a sound therapeutic strategy.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Hemagglutination and graft-versus-host disease in the severe combined immunodeficiency mouse lymphoproliferative disease model.

In the course of evaluating the severe combined immunodeficiency mouse-human peripheral blood lymphocyte (SCID-PBL) model of lymphoproliferative disease, we noted hemagglutination occurring in peripheral blood smears of mice with serum human immunoglobulin levels greater than 1.0 mg/ml. The hemagglutinating process was mediated by human anti-mouse red cell antibodies of the IgM class, peaked at five to seven weeks post-transfer of 5 to 7 x 10(7) human PBL and was generally self limiting. However, death resulted in some mice when serum immunoglobulin levels were greater than 3.0 mg/ml. The most severely affected mice had hemagglutination induced congestion of liver, lungs and spleen. Several mice also had lesions consistent with graft-versus-host disease (GVHD) including focal hepatic necrosis and destruction of mouse splenic hematopoietic elements. The lesions associated with hemagglutination and GVHD in SCID-PBL mice are distinct from those associated with EBV-induced lymphoproliferation. Recognition of these pathologic processes are required for a thorough understanding of the SCID-PBL model.

Animals↗
PubMed1979

Immunological bases for superior survival of females.

Evolutionary selection has equipped females with immunoregulatory genes on the X chromosome for coping with life-threatening illness. Five immunodeficiency syndromes occur solely in males, suggesting that they arise from mutant immunoregulatory genes located on the X chromosome. These syndromes, although rare, could contribute to poorer survival of males. Females have higher serum IgM concentrations, superior ability to form antibodies to infectious agents, and experience a lower incidence of viral and bacterial infectious diseases. Preponderance of autoimmune disorders in females could arise from modified immune responses owing to estrogens. Clinical and animal studies indicate that male hormones suppress autoantibody production whereas female hormones support their production. Superior immunocompetence and survival of females is based, in part, on their being protected from mutant immunoregulatory genes located on the X chromosome.

Animals↗
PubMed1978

Epstein-Barr virus infections in the X-linked recessive lymphoproliferative syndrome.

Prospective studies demonstrated variable phenotypic expression of the X-linked recessive lymphoproliferative syndrome (X.L.R.L.S.) in three brothers: (1) hypogammaglobulinaemia and subclinical Epstein-Barr-virus (E.B.V.) infection with antibody response to E.B.V.; (2) E.B.V. infection with defective immune response to E.B.V., fatal infectious mononucleosis (I.M.), and immunoblastic lymphoma; and (3) histiocytic lymphoma. Hypogammaglobulinaemia and measles pneumonitis had preceded infection with E.B.V. The diverse phenotypic expressions probably resulted from the varied immune response to E.B.V. Recombination of X chromosomes was documented by Xg-blood-group studies in a survivor. E.B.V. can induce fatal I.M. and malignant lymphoma in X.L.R.L.S., but an immune response to E.B.V. can be protective.

Adolescent↗