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D T Purtilo

Publications and source records attributed to D T Purtilo.

At least 127 records · Page 7Linked to original sources
PubMed1984

Chronic mononucleosis syndrome.

We present data on 14 patients with chronic symptoms of disabling fatigue in association with serologic evidence of active Epstein-Barr virus (EBV) infection. Two thirds were women, and the average age at onset was 29.6 years. Forty-three percent were known to have had previous infectious mononucleosis, but the usual criteria for that diagnosis were not helpful with the present syndrome. Eighty-six percent had serologic evidence of cytomegalovirus (CMV) infection. Profound immunodeficiency was not present, but 71% had partial hypogammaglobulinemia, and minor abnormalities of T cell subsets were noted in six of seven patients studied. Fifty-seven percent achieved temporary serologic and symptomatic remission after an average duration of 33 months. Only one patient has a sustained remission. Comparison is made with other reported chronic, recurrent, and persistent EBV syndromes, and tentative diagnostic criteria for chronic mononucleosis syndrome are presented. Recently available EBV serologic techniques allow for identification of patients who have reactivated EBV infection, and this reactivation may be related to symptoms.

Adolescent↗
PubMed1984

Delayed onset of infectious mononucleosis associated with acquired agammaglobulinemia and red cell aplasia.

In 1974, an 11-year-old white boy with the X-linked lymphoproliferative syndrome developed hyper-IgM after becoming infected with Epstein-Barr virus. However, he failed to develop normal immune responses against the virus. In December 1981, when red cell aplasia occurred, he was given packed erythrocytes and gammaglobulin. Nine weeks later, acute infectious mononucleosis developed. Concurrently, his T4/T8 helper/suppressor ratio decreased from 2.7 to 0.2, and IgM antibodies to Epstein-Barr virus appeared. Subsequently, circulating B cells became undetectable in his blood, and agammaglobulinemia appeared. Red cell aplasia abated transiently. This patient's course was complicated by Haemophilus influenzae and Mycobacterium tuberculosis pneumonias, and red cell aplasia and agammaglobulinemia have persisted. Epstein-Barr virus acting as a slow virus probably induced the red cell aplasia and agammaglobulinemia because of the aberrant immune responses to Epstein-Barr virus. Immunodeficient responses to Epstein-Barr virus should be sought in other patients with the diseases documented in our patient.

Agammaglobulinemia↗
PubMed1984

Infection of normal human thymic epithelial cells by Epstein-Barr virus (EBV) following implantation of EBV receptors.

Normal human thymic epithelial cells cannot be infected and transformed by Epstein-Barr virus (EBV). Measurements using fluorescein-labelled EBV and cytofluorograph revealed that the cells do not have receptors for the virus. Following transplantation of functional EBV receptors onto epithelial cell membranes, however, the cells were infected with EBV and expressed EBV-determined nuclear antigen (EBNA). No EBV associated antigens characteristic of the lytic cycle of the virus were detected. This method of in vitro infection by transforming viruses such as EBV may provide ways of deriving functioning thymic epithelial cell lines.

Antigens, Viral↗
PubMed1984

Squamous-cell carcinoma, Kaposi's sarcoma and Burkitt's lymphoma are consequences of impaired immune surveillance of ubiquitous viruses in acquired immune deficiency syndrome, allograft recipients and tropical African patients.

The immune system has evolved under Darwinian pressures as a defence against ubiquitous viruses. Immune surveillance against viral antigens protects the normal host. Individuals with inherited or acquired immune-deficiency disorders can become vulnerable to ubiquitous viruses and neoplasms can ensue, such as B-cell lymphoma, hepatocellular carcinoma, squamous-cell carcinoma, Kaposi's sarcoma, and carcinoma of the penis and uterine cervix. Immunodeficiency permits Epstein-Barr virus, hepatitis B virus, papillomavirus, herpes simplex virus, and cytomegalovirus to induce sustained target-cell proliferation. Each virus selects specific cellular targets bearing viral receptors and the infection leads to proliferation of the target cells rather than lysis. Various co-factors, including nutrition, exposure to tumour-promoting agents, parasitic infection, and ultraviolet light, may promote carcinogenesis. Depending on the type and severity of the immune deficiency, gradual proliferation may lead to evolution of a malignant clone. Conversion of polyclonal virally infected proliferating cells to give monoclonal malignancy is probably due to specific cytogenetic rearrangements which allow oncogene activation and endow an altered tumour cell with selective growth advantages over normal diploid cells. Prevention of viral oncogenesis may be possible by treatment of immune-deficient individuals with premalignant disorders. Immunotherapy and antiviral therapy may prevent progression of viral-induced proliferation to malignancy. The purpose of this paper is to discuss and evaluate the role of immune deficiency and viruses in the induction of malignancies commonly occurring in Africans residing in sub-Saharan Africa (Purtilo, 1976). The types of malignancies commonly occurring in this region are believed to be due to ubiquitous viruses. A failure of immune surveillance mechanisms to recognize viral antigens and abrogate proliferation of infected target cells predisposes to malignancy by increasing the chance of a proliferating cell undergoing a cytogenetic or molecular alteration which endows it with malignant characteristics. The immunological surveillance hypothesis has been elaborated during this century by Ehrlich, Thomas, Burnet, and Schwartz (reviewed by Purtilo & Linder, 1983). This hypothesis rests on several assumptions: that neoplastic cells possess unique tumour antigens: tumour antigens provoke an immune response in the host; and the immune response is protective and eliminates the tumour.(ABSTRACT TRUNCATED AT 400 WORDS)

Acquired Immunodeficiency Syndrome↗
PubMed1984

Immunodeficiency as a factor in lymphomagenesis.

The human immune system has evolved multiple cellular and humoral defense mechanisms against the lymphotropic virus, EBV. NK cells, suppressor T-cells, cytotoxic K-cells, memory T-cells, and humoral immune responses usually subdue the virus into latency. Individuals with immune deficiency are at great risk of developing immunoregulatory disturbances and lymphoproliferative diseases when confronted by EBV. The infection of B-cells by EBV provokes a marked activation of immunoregulatory T-cells and requires restoration of immune homeostasis during convalescence. This is accomplished with difficulty in an individual with significant immune defects. The X-linked lymphoproliferative syndrome is an exemplary model for studying EBV in immune deficient individuals. Boys with XLP can develop acquired agammaglobulinemia, aplastic anemia, chronic or fatal IM, and a variety of B-cell malignant lymphomas following infection by the virus. We have identified multiple immune defects in the patients and progressive immunoregulatory disturbances following infection by the virus. Other patients with immune deficiency syndromes, i.e., ataxia telangiectasia or the renal transplant recipient, are also at increased risk for developing EBV-induced lymphoproliferative diseases. Moreover, certain families are at increased risk for EBV-associated malignancies, especially those with a triad of manifestations (i.e., autoimmunity, immunodeficiency, and lymphoma). Chromosomal breakage as seen in patients with ataxia telangiectasia may predispose to leukemogenesis. Immunoregulatory defects are also probably predisposing factors to lymphomagenesis. Both inherited and acquired defects can render persons vulnerable to leukemia and lymphoma.

Burkitt Lymphoma↗
PubMed1984

Cancer cytogenetics.

Explore the source record for details and available documents.

Chromosome Aberrations↗
PubMed1984

Transformation of Fanconi's anemia to acute nonlymphocytic leukemia associated with emergence of monosomy 7.

Two sisters in whom a diagnosis of Fanconi's anemia was made at ages 12 and 18 subsequently developed acute nonlymphocytic leukemia (ANLL). A third sibling had previously died at age 11 of apparent sepsis. Both sisters had cytogenetic studies that showed increased chromosomal breakage and a 46,XX karyotype, but subsequently developed ANLL after, or coincident with, the emergence of monosomy 7. These observations suggest that, in addition to myelodysplastic syndromes and defective neutrophil chemotaxis, monosomy 7 may be associated with the emergence of leukemia in this disorder.

Acute Disease↗
PubMed1983

Acquired immunodeficiency syndrome, opportunistic infections, and malignancies in male homosexuals. A hypothesis of etiologic factors in pathogenesis.

The acquired immunodeficiency syndrome (AIDS) occurs in a subgroup of male homosexuals having sexual contact with a large number of partners. Uncommonly, AIDS has also been diagnosed in Haitians, hemophiliacs, and intravenous drug users and their infants. Manifestations include autoimmune disturbances, opportunistic infections, Kaposi's sarcoma, chronic lymphadenomegaly, non-Hodgkin's lymphoma, or squamous cell carcinoma. The hypothesis receiving most consideration is that a yet-to-be-identified virus causes AIDS. An alternative view is that repeated sexual involvement with multiple partners, in a subgroup of male homosexuals, exposes the men to the immunosuppressive impact of cytomegalovirus (CMV) and allogeneic semen. Antibody to asialo-Gm1 and other antigens on sperm react with and impair lymphoid cells. We propose a biphasic process. First, a reversible acquisition phase of impaired T-cell immunoregulation permits reactivation of Epstein-Barr virus (EBV), and autoantibodies are produced by the activated B cells. If sexual activity continues at a high level, accumulating immune defects, including destruction of thymic epithelium, lead to a second, self-sustaining phase wherein cytotoxic lymphocytes fail to eliminate herpesvirus-infected cells. Evidence is mounting that Kaposi's sarcoma is caused by CMV and that EBV is responsible for the B-cell lymphomas in these patients. Multiple factors, rather than a novel virus, probably induce AIDS in male homosexuals. If this hypothesis is correct, then rational bases for prevention and intervention can be designed.

Acquired Immunodeficiency Syndrome↗
PubMed1983

Oncological consequences of impaired immune surveillance against ubiquitous viruses.

The immune system is constantly challenged by ubiquitous viruses. Multiple immune defenses have evolved to meet these challenges, and thus immunocompetent individuals successfully respond to infection without sequela. X-linked lymphoproliferative syndrome patients, renal allograft recipients, and acquired immunodeficiency syndrome patients share impaired immune surveillance as a common feature. Such individuals are variously susceptible to numerous untoward complications following infection with Epstein-Barr virus, cytomegalovirus, herpes simplex virus, human papillomavirus, and hepatitis B virus. We hypothesize that failure of the immune system to control these viruses is instrumental in the occurrence of some B-cell lymphomas. Kaposi's sarcoma, and squamous-cell and hepatocellular carcinomas. Herein we review some mechanisms responsible for the breakdown of immune surveillance and the permissive role immunodeficiency plays in viral oncogenesis.

Acquired Immunodeficiency Syndrome↗
PubMed1983

Lymphocyte abnormalities in preleukemia--I. Decreased NK activity, anomalous immunoregulatory cell subsets and deficient EBV receptors.

The development of acute non-lymphocytic leukemia is preceded by a set of symptoms described as the preleukemia syndrome. Six patients who fulfilled the criteria for this preleukemia syndrome have been evaluated for abnormalities in the lymphocyte population. The NK cell activity was reduced, the immunoregulatory cell populations were numerically abnormal, and the B cell subpopulation was deficient in EBV receptors. Thus, in addition to the abnormalities in the myeloid populations, there are serious defects in the lymphoid systems of preleukemic patients.

Adult↗
PubMed1983

Induction of antibody to asialo GM1 by spermatozoa and its occurrence in the sera of homosexual men with the acquired immune deficiency syndrome (AIDS).

Compared to healthy homosexual and heterosexual men, homosexual men with acquired immune deficiency syndrome (AIDS) possessed significantly higher levels of IgG antibody to the neutral glycolipid asialo GM1 (ganglio-N-tetraosylceramide) (P less than 0.01). Of 31 homosexuals with AIDS, 36% possessed levels of this antibody that were at least two standard deviations above the mean of the healthy men. Furthermore, asialo GM1 antibody could be removed from serum by adsorption with spermatozoa. Weekly rectal insemination of male rabbits with rabbit semen also led to the appearance of antibody to asialo GM1 by 15 weeks. These results suggest that asialo GM1 is a component of ejaculated spermatozoa and demonstrate that rectal insemination by itself can lead to the production of antibodies to this glycolipid in the rabbit. In addition, asialo GM1 antibodies may be of value as a serological marker for the early detection of individuals with AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1982

Cell-mediated immunity to Epstein-Barr virus (EBV) and natural killer (NK)-cell activity in the X-linked lymphoproliferative syndrome.

The activity of T-cell-mediated immunity to Epstein-Barr virus (EBV) was assessed by an assay of regression of the outgrowth of EBV-infected autologous B cells. Regression and natural killer (NK)-cell activities were compared for patients and their mothers from five families with X-linked lymphoproliferative syndrome (XLP) and three control groups. Seven of the 10 patients with XLP exhibited weak T-cell activity against autologous EBV-infected lymphoblastoid cell lines (LCL) comparable to EBV-seronegative controls. In contrast, 8 of 10 obligate carrier females of XLP had unusually strong activity, which was comparable to anti-early-antigen (EA) positive controls. The results of the regression assays correlated with their EBV serology: mothers showed high titers, and their affected sons showed low-titer EBV-specific antibody responses. Defective NK-cell activity was found only in the patients with XLP. NK and regression activities did not correlate. Our findings explain, in part, the vulnerability to EBV of males with XLP and why their mothers are protected from life-threatening phenotypes of XLP.

Antibodies, Viral↗