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Biomedical subjects

D T Purtilo

Publications and source records attributed to D T Purtilo.

At least 73 records · Page 4Linked to original sources
PubMed1987

Malignant lymphoma in the X-linked lymphoproliferative syndrome.

Male patients with the X-linked lymphoproliferative syndrome (XLP) have an inherited immune deficiency to Epstein-Barr virus (EBV) infection that results in fatal infectious mononucleosis (IM), acquired hypogammaglobulinemia- or agammaglobulinemia, virus-associated hemophagocytic syndrome, and non-Hodgkin's malignant lymphoma (ML). A clinicopathologic analysis of 17 patients with XLP who developed ML was performed. The median age of the patients at the time of diagnosis was 4.0 years (range, 2-19 years). The median overall survival was 12 months (range, 1-216 months). Eight patients had maternally related male relatives with ML. Other phenotypes of XLP were documented in male relatives of the remaining nine patients. Common presenting symptoms were fever, nausea, vomiting, and abdominal pain. Nine patients had "B" symptoms. All ML occurred at extranodal sites. The intestines, most commonly ileocecal, were involved in 76.5% of the cases. Thirteen patients had localized disease (Stages I and II) and four patients had advanced disease (Stages III and IV). A diffuse histologic pattern of growth was observed in all cases. The distribution of histologic subtypes included small noncleaved (41.2%), large noncleaved (17.6%), immunoblastic (17.6%), small cleaved or mixed cell (11.8%), and unclassifiable (5.9%) ML. Surgical resection, radiation therapy, and chemotherapy resulted in disease-free survivals of up to 192 months in eight patients (median 114 months; range, 12-192 months). Eight of 17 patients (47%) are still alive. A median survival of only 6.0 months (range, 1-12 months) was observed in the nine patients who died. No residual ML was found at autopsy. The small noncleaved subtype had an adverse prognosis (seven of nine deaths versus one of eight survivors; P less than 0.05). Bacterial infection was the major cause of death (seven of nine patients). Characteristics that distinguish ML in XLP from other ML include a maternal family history of XLP, early age of onset, acquired hypogammaglobulinemia, post-EBV infection, and ileocecal involvement.

Actuarial Analysis↗
PubMed1987

Reactive T cells in the immune repertoire: self-restricted and allo-restricted helper T-cell clones to Epstein-Barr virus.

Helper T-cell clones were generated by stimulation with autologous or allogeneic lymphoblastoid B cells (B-LCL) transformed by the Epstein-Barr virus (EBV). Some of these T-cell clones were allo-reactive and others were specific to EBV-transformed B-LCL. Helper T-cell clones specific to EBV-transformed B-LCL were restricted either by class-I or by class-II HLA molecules of self. T-cell clones restricted by class-I HLA molecules were stained by OKT3 and OKT8 monoclonal antibodies (MAbs), whereas class-II-restricted clones stained with OKT3 and OKT4. Not all helper T-cell clones specific to EBV-transformed B-LCL were restricted to self: one clone restricted by allo-HLA antigen was established. This finding suggests that in humans, as in mice, some T cells in the T-cell repertoire can be allo-restricted. This allo restriction may represent cross-reactivity of T cells, whereby "self + X" equals "allo + Y." Activation of these cross-reacting T cells restricted by allogeneic HLA molecules during infectious mononucleosis will give a T-cell response which may appear unrestricted by self HLA molecules. This mechanism helps to explain, at least in part, the HLA unrestricted cytotoxicity to B-LCL observed in infectious mononucleosis.

Antigens, Surface↗
PubMed1987

Graft versus host disease following transfusion of normal blood products to patients with malignancies.

A patient undergoing treatment with cytotoxic chemotherapy for Hodgkin's disease developed graft versus host disease (GVHD) following a transfusion of packed red cells. This is the 28th reported patient with a malignancy who did not have a bone marrow transplant and developed GVHD after transfusion of normal blood or blood products. All patients had received cytotoxic chemotherapy prior to acquiring GVHD. The underlying malignancies included lymphoma, acute leukemia, neuroblastoma, rhabdomyosarcoma, and glioblastoma. Twenty-three of the 28 patients died of GVHD. The incidence of transfusion-related GVHD in this patient population is low but the illness is often fatal as treatment is largely ineffective. Transfusion-related GVHD can be prevented by irradiating all blood products with 1500 rad prior to administration.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1987

Cutaneous necrotizing granulomatous vasculitis with evolution to T cell lymphoma.

The evolution of unusual cutaneous vasculitis to a systemic T cell lymphoma was observed over a 12-year period. Precise classification of the skin biopsy specimens during the course of this patient's illness was difficult. Different observers suggested malignant hemangioendothelioma, malignant lymphoma, regressing atypical histiocytosis, and granulomatous vasculitis. In retrospect, the biopsy specimens likely represented the spectrum of cutaneous lymphomatoid granulomatosis. This condition is yet another example of a reactive lymphoid proliferation proceeding to a malignant lymphoma.

Diagnosis, Differential↗
PubMed1987

Hepatitis in fatal infectious mononucleosis.

A detailed clinicopathologic analysis of 30 patients with sporadic fatal infectious mononucleosis and 31 males with fatal infectious mononucleosis and the X-linked lymphoproliferative syndrome was performed to determine the extent of hepatic dysfunction in these cases. At death, the median age of patients with sporadic infectious mononucleosis was 10.7 yr vs. 2.4 yr for X-linked lymphoproliferative syndrome. The median survival time was 8 wk for sporadic infectious mononucleosis and only 4 wk for X-linked lymphoproliferative syndrome. The male to female ratio was 3:2 in sporadic infectious mononucleosis; all patients with X-linked lymphoproliferative syndrome were males. Fever, sore throat, lymphadenopathy, hepatomegaly, and splenomegaly were prominent findings. Hepatic dysfunction was uniformly present and caused death in 13 of 30 sporadic infectious mononucleosis cases and 18 of 31 X-linked lymphoproliferative syndrome cases. Diagnosis of infectious mononucleosis was confirmed by heterophile antibody titers or Monospot, Epstein-Barr virus antibody studies, viral culture, molecular hybridization studies, clinical and histologic findings, and pedigree analysis.

Child↗
PubMed1987

Thymic lesions in fatal infectious mononucleosis.

Thymic lesions were studied in 35 patients with fatal infectious mononucleosis (FIM) including 21 males with the X-linked lymphoproliferative syndrome (XLP) and 14 non-XLP patients. Six patterns based on the lymphocyte content and status of Hassall's bodies were observed: massive lymphoproliferation effaced the architecture and Hassall's bodies (HB) in 6 cases. Epstein-Barr virus (EBV)-laden B cells surrounded by cytotoxic T cells and natural killer cells were found in one of these cases. Only 5 of the 35 thymuses contained normal-appearing HB. Seven showed a moderate reduction in HB. Rarely, multinucleated giant cells and hyaline globules were seen where one might expect HB to reside. Plasma cells and macrophages were generally abundant. Eight displayed a marked depletion of HB. In 7, no HB were recognized. Massive necrosis was seen in one of these cases. Stress involution was encountered in only two patients, both of whom had sporadic fatal IM. Thymic lesions and alterations were similar but less extensive in sporadic FIM. These morphological studies, taken in context with clinical and experimental reports, suggest that destruction of thymic epithelium may contribute to the progression of immune defects seen in XLP following EBV infection. The destruction of HB that we observed was similar in appearance to lesions in several other immune deficiency disorders.

Age Factors↗
PubMed1987

Mucinous colon carcinoma in a black family.

Carcinoma of the large bowel developed in an autosomal dominant pattern in 13 members of a black-American family. Seven members were affected prior to initial ascertainment of the family in 1976. Thereafter, the remaining six were affected while 0.2 cases were expected (p less than 0.001). Median age at diagnosis of colon cancer was 39 years (range, 22-62 years) in this family, compared with 65 years among black-Americans, in general. Histologic review of surgical specimens from six patients and medical record data for a seventh patient showed mucinous adenocarcinoma of the colon, an uncommon histologic variant. Studies of several family members a decade ago had revealed no biologic markers of cancer susceptibility.

Adenocarcinoma, Mucinous↗
PubMed1987

Rapid detection of cytomegalovirus by tissue culture, centrifugation, and immunofluorescence with a monoclonal antibody to an early nuclear antigen.

A rapid, sensitive and specific assay for the detection of cytomegalovirus (CMV) was developed utilizing MRC-5 cells in 24-well plates containing round coverslips. Centrifugation expedited the detection of CMV early antigen with monoclonal antibody. Immunofluorescent staining 16 h after inoculation with a stock CMV preparation (AD-169), demonstrated an 11-fold increase in the number of nuclear inclusions when the specimens were centrifuged (18 +/- 2.2) as compared to the non-centrifuged specimen (1.6 +/- 0.9). However, the number of nuclear inclusions depended on the age of the MRC-5 cells. They were more sensitive to CMV infection between 4 and 11 days after the cells were seeded into plates. Among 159 patient samples cultured for CMV, 23 (14%) were positive by the rapid method (mean of 32 h) and 18 (11%) by routine tissue culture (mean of 12 days). Cytomegalovirus in urine was detected within 1.3 days, whereas buffy coats (2.3 days) and bronchial washings (2.5 days) took longer. Staining for CMV inclusions at more than one time point was necessary for the optimal detection of CMV by the rapid method. We recommend using this assay system as it is rapid, specific, sensitive and versatile for the detection of CMV in many biological specimens.

Antibodies, Monoclonal↗
PubMed1987

Malignant lymphoma in Nebraska and Guangzhou, China: a comparative study.

Two hundred thirty-four consecutive cases of malignant lymphoma (192 non-Hodgkin's lymphomas and 42 Hodgkin's disease) from Guangzhou, China, and 589 cases (498 non-Hodgkin's lymphomas and 91 Hodgkin's disease) from the University of Nebraska Lymphoma Registry were examined in a retrospective histopathologic analysis and the results compared to those of the National Cancer Institute (NCI) Working Formulation Summary. Aggressive non-Hodgkin's lymphoma was excessive in Guangzhou (82.3 per cent; P less than 0.001) and Nebraska (80.3 per cent; P less than 0.001) when compared with the NCI data (54.2 per cent). The small noncleaved cell, lymphoblastic, and diffuse mixed-cell subtypes were more frequent in China (15.6 per cent each; P less than 0.001), whereas the small lymphocytic, follicular large cell, and immunoblastic subtypes predominated in Nebraska (8 per cent, 8.4 per cent, and 21.8 per cent, respectively; P less than 0.001). The overall median age of onset for non-Hodgkin's lymphoma was 42.0 years in Guangzhou and 63.5 years in Nebraska. Hodgkin's disease represented 18 per cent of the malignant lymphomas in Guangzhou and 15 per cent in Nebraska. The mixed-cellularity type was most common in Guangzhou (52 per cent; P less than 0.001) and the nodular-sclerosing type in Nebraska (56 per cent; P less than 0.010). The low median age and excess of certain aggressive subtypes of non-Hodgkin's disease in Guangzhou suggest a possible viral etiology, whereas the excess of certain subtypes of non-Hodgkin's lymphoma in Nebraska may be related to intense agricultural activity.

Adult↗
PubMed1987

Epstein-Barr virus: the spectrum of its manifestations in human beings.

Epstein-Barr virus (EBV) infects virtually everyone by adulthood, and a lifelong latency is maintained. It infects children silently, whereas the majority of adolescents have infectious mononucleosis (IM). Children who have IM before 5 years of age are often heterophil negative; EBV-specific antibodies are required for diagnosis. On rare occasions the symptoms of IM may persist in a chronic or recurrent form, and fatal infectious mononucleosis occurs rarely. Depending on the type and degree of immune deficiency and the time the EBV infection occurs in the life cycle, various atypical outcomes can occur. Children with primary immune deficiency can have fatal or chronic IM, malignant B cell lymphoma, virus-associated hemophagocytic syndrome, aplastic anemia, or acquired hypogammaglobulinemia. The various outcomes of the EBV infections are likely governed by the immune response of the individual. The increased frequency of B cell neoplasms in immunodeficient patients is likely due, in part, to EBV. Individuals with acquired immune deficiency disorders such as AIDS or allograft recipients may develop malignant B cell lymphomas which tend to be polyclonal, but which may progress through stages of oligoclonality to monoclonality. This conversion likely results from specific reciprocal chromosomal translocations such as t(8;14), which is seen in Burkitt's lymphoma. Detection of EBV in immunodeficient patients is achieved by EBV-specific antibody studies or isolation of virus by obtaining spontaneous lymphoblastoid cell lines from peripheral blood, isolating virus from throat washings, or identifying EBV genome by molecular hybridization techniques. Prevention of primary immune deficiency by early detection and genetic counseling and monitoring of patients for occurrence of EBV infection may lead to early treatment. Acyclovir and immunoglobulin therapy can be of value in some patients with active EBV infection.

Adolescent↗
PubMed1987

Immunoregulatory T cells in males vulnerable to Epstein-Barr virus with the X-linked lymphoproliferative syndrome.

The X-linked lymphoproliferative syndrome (XLP) is a primary immune deficiency. Affected males are vulnerable to fatal infection by Epstein-Barr virus (EBV). In patients who had survived an infection by EBV, helper and cytotoxic T cells reactive to virus-transformed autologous B lymphoblastoid cells were infrequent. This was similar to that observed in normal individuals seronegative to EBV. In contrast, frequencies of the reactive T cells were high in normal controls seropositive to EBV. Patients with XLP also had a propensity to activate radiosensitive suppressor cells when their T cells were stimulated by EBV transformed B cells. Hence, clonal expansion of helper and cytotoxic T cells to virus-transformed B cells failed to occur during an EBV infection in these patients because of immunosuppression. These defects in the T cell repertoire of patients with XLP may predispose them to be susceptible to EBV-induced lymphoproliferation and contribute to the variability in expression of the phenotypes seen in these patients.

Adolescent↗
PubMed1987

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

A registry of persons with the X-linked lymphoproliferative syndrome, which is characterized by marked susceptibility to diseases induced by the Epstein-Barr virus, has enrolled 161 patients within 44 kindreds. Fifty-seven percent of the males died of infectious mononucleosis, 29% developed acquired hypogammaglobulinemia, and 24% had malignant lymphoma. The mortality rate was 80%; 70% died by 10 years of age and 100% by 40 years. Thirty-two boys survive, most with malignant lymphoma, acquired hypogammaglobulinemia, or both. We hypothesized that the defective lymphoproliferative control locus on the X chromosome results in unregulated cytotoxic lymphocytic responses to the Epstein-Barr virus; hence, severe hepatitis and virus-associated hemophagocytic syndrome occur with the infectious mononucleosis phenotype. T-cell suppression of immunoglobulin secretion by B cells is responsible for acquired hypogammaglobulinemia. A sustained polyclonal B-cell proliferation probably converts to a monoclonal B-cell malignancy as a result of molecular alterations.

Adolescent↗
PubMed1987

Epstein-Barr viral DNA in tissues of Hodgkin's disease.

Tissue specimens from 21 cases of Hodgkin's disease were examined for the presence of Epstein-Barr virus (EBV) and cytomegalovirus DNA by molecular hybridization techniques. EBV DNA was detected in 4 cases, including 2 of 8 cases which had been previously shown to contain clonal immunoglobulin gene rearrangements. Two of the cases containing EBV DNA were of the nodular sclerosing type and had received prior therapy; the other 2 were classified as mixed cellularity Hodgkin's disease and had not received therapy before the biopsy tissue was obtained. Analyses of the terminal portions of EBV genomes indicated a monoclonal or oligoclonal proliferation of EBV-infected cells in the tissues studied. In contrast, none of the 21 cases had detectable cytomegalovirus DNA sequences. The identification of EBV DNA may reflect the proliferation of lymphoblastoid cells due to the reduced immune competence frequently noted in Hodgkin's disease or may indicate the presence of EBV genomes within Reed-Sternberg cells.

Adult↗
PubMed1987

Opportunistic cancers in patients with immunodeficiency syndromes.

Patients with inherited or acquired immunodeficiency disorders are vulnerable to a broad spectrum of opportunistic infectious diseases, but a narrow spectrum of malignancies. These malignancies--B-cell lymphomas, Kaposi's sarcomas, and squamous cell carcinomas--are likely due to failure of immune surveillance to recognize virally transformed target cells. The evidence for this hypothesis is substantial regarding Epstein-Barr virus-induced lymphoproliferative lesions in immunodeficient patients.

Acquired Immunodeficiency Syndrome↗
PubMed1987

X-linked lymphoproliferative syndrome provides clues to the pathogenesis of Epstein-Barr virus-induced lymphomagenesis.

X-linked lymphoproliferative disease (XLP) is a rare genetic syndrome that continues to serve as a useful model to understand more broadly the role of immunodeficiency and the pathogenetic mechanisms for the spectrum of Epstein-Barr virus (EBV)-induced diseases to which XLP is predisposed. Apart from XLP, EBV infection is related to the high frequency of non-Hodgkin's lymphoma in children with various primary immune deficiency diseases and in allograft recipients. More recently, EBV has been implicated in several lymphoproliferative diseases in individuals with acquired immune deficiency syndrome. Studies thus far on patients with XLP suggest that immune deficiency is a major determinant of these diseases. Additional molecular aberrations must be necessary in the pathogenesis of lymphoma to convert polyclonal to monoclonal disease.

Female↗
PubMed1987

Ontogeny and regulation of the immune system.

Classic studies in embryology and contemporary research in immunology and molecular biology have disclosed the carefully orchestrated events leading to development of the immune system and immunoregulation that ultimately provide immunohomeostasis. During ontogeny, the pluripotential stem cell emerges and differentiates into all hematopoietic lineages, including three major immunologically relevant components: T-cell differentiation occurs within the thymus; B cells appear within fetal liver, adult bone marrow, and possibly other abdominal sites; and concurrently, the monocyte-macrophage system develops. Under the influence of an array of cytokines and cellular interactions, immune regulation is established. T and B lymphocytes elaborate genetically encoded messages that acquire specificity via transposable genetic elements. Receptors and cytokines provide immune recognition, communication, regulation, and memory for antigens. Inherited and acquired defects in ontogeny and immune regulation are the basis for immunodeficiency disorders.

Animals↗
PubMed1987

New developments in AIDS.

At the present time there is no effective therapy for the HIV infection itself, nor for the opportunistic infections, malignancies, immune perturbations, and other manifestations of AIDS. However, as a result of knowledge gained regarding the modes of transmission of HIV, public health officials have made recommendations which, if followed, would slow or even halt further spread of the virus. Thus it is hoped that educational efforts directed at individuals in high-risk groups will be effective in stopping transmission of this disease and that ongoing research efforts will soon provide therapeutic agents to cure it or slow its progression.

Acquired Immunodeficiency Syndrome↗