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Biomedical subjects

D Variakojis

Publications and source records attributed to D Variakojis.

At least 55 records · Page 3Linked to original sources

The spectrum of human immunodeficiency virus infection in patients with factor IX deficiency (Christmas disease)

Early reports suggested that hemophiliacs with factor IX deficiency (Christmas Disease) may be at less risk for developing the acquired immunodeficiency syndrome (AIDS) than patients with classic hemophilia. We evaluated 12 factor IX deficient patients for clinical and immunologic abnormalities related to infection with the human immunodeficiency virus (HIV). Antibody to HIV was not detected in these patients prior to 1982. By 1985, 66 percent (eight of 12) patients were seropositive. All three concentrates available commercially before 1985 were associated with seropositivity. Furthermore, seropositive hemophiliacs had received on average significantly more factor IX concentrate than seronegative hemophiliacs (27,825 +/- 17,976 (S.D.) versus 1,250 +/- 1,500 factor units/year, (p less than 0.02). Half of the seropositive individuals had generalized lymphadenopathy with splenomegaly. Two seropositive patients have developed AIDS, one with cryptococcal meningitis and another with a large cell immunoblastic lymphoma. Infection with HIV has occurred with high frequency in hemophiliacs who received unmodified factor IX concentrates.

AIDS-Related Complex↗

Radioimmunodetection and radioimmunotherapy of cutaneous T cell lymphomas using an 131I-labeled monoclonal antibody: an Illinois Cancer Council Study.

A radiolabeled murine monoclonal antibody (T101) was used for imaging and therapy of six patients with cutaneous T cell lymphoma (CTCL). Radioimmunodetection was performed with a 5.6 to 13.1 mCi 131I-T101 preparation (9.6 to 10.5 mg). A therapeutic dose of 100.5 to 150.1 mCi 131I on 9.9 to 16.9 mg of antibody was administered to five patients, with subsequent retreatment following plasmapheresis in three patients at the time of disease progression. All patients responded to their initial therapy and two patients responded to retreatment. Regression of skin lesions and peripheral adenopathy was witnessed. All patients reported resolution of their chronic pruritus. The duration of response ranged from 3 weeks to 3 months. Acute toxicity included fevers, pruritus, and mild dyspnea in two instances. Myelosuppression was seen in patients receiving the 144.7 mCi, 145.0 mCi, and 150.1 mCi 131I-T101 doses. Radioimmunodiagnostic and therapy studies included gamma scintigraphy, plasma, urinary, and wholebody antibody clearances, and biodistribution determined from skin, bone marrow, and liver biopsies. Immunologic studies included immunoperoxidase staining of target tissues, immunofluorescent flow cytometric analysis on peripheral blood and bone marrow, assays for serum blocking factors, determination of a human antimouse antibody (HAMA) response, and quantitation of circulating T101 levels. These preliminary data suggest that 131I-T101 has therapeutic potential in CTCL and that myelosuppression will be the limiting toxicity.

Aged↗

Human T-cell lymphotropic virus type I-associated adult T-cell leukemia/lymphoma in an atypical host.

Human T-cell lymphotropic virus type I (HTLV-I) is a unique retrovirus associated with specific malignancies of T cells in humans. The virus is endemic to Japan, the Caribbean, Africa, and the southeastern United States. We report here the first case of HTLV-I-associated lymphoma in an atypical host. The incidence of antibodies in this individual with a T-cell malignancy strongly suggests HTLV-I virus as the causative agent. Direct identification of viral DNA using an HTLV-I-specific probe provides definitive evidence of infection.

Aged↗

DNA aneuploidy in Hodgkin's disease. A multiparameter flow-cytometric analysis with cytologic correlation.

In 15 cases of Hodgkin's disease, the authors studied the DNA content of isolated nuclei from deparaffinized tissue by using multiparameter flow cytometry. An antinucleolar antibody preparation was employed as well as a secondary antibody that had been conjugated with fluorescein isothiocyanate. By simultaneously quantitating nucleolar fluorescence and DNA content, rare but distinct aneuploid populations were detected among the nuclei with brightly stained nucleoli. DNA aneuploidy was found in each case when this multiparameter analysis was used, but was detected in only 1 case when DNA content was analyzed alone. With the multiparameter analysis, two to four aneuploid populations were found in each case. These populations exhibited incremental duplications of DNA content that suggested endopolyploidy, ie, replication of DNA without accompanying nuclear division. The aneuploid stem line was hypodiploid or hypotetraploid in 6 cases, hyperdiploid in 7 cases, and near-triploid in 2 cases. These various abnormalities in ploidy showed only some correlation with histologic subtypes. Cell sorting showed that some nuclei with more than four or nearly eight times normal DNA content resembled nuclei of typical Reed-Sternberg cells. Many nuclei with an intermediate aneuploid DNA content resembled nuclei of mononuclear Reed-Sternberg cells. The near-diploid and near-triploid nuclei corresponded to nuclei of cells which were not readily recognizable as neoplastic in histologic sections. It is concluded that multiparameter analysis of DNA content can provide further insights into the neoplastic cells in Hodgkin's disease and may offer an objective basis for studying heterogeneity in this disorder.

Aneuploidy↗

Successfully treated Hodgkin's disease followed by mycosis fungoides: case report and review of the literature.

We report the case of a 30-year-old man who had Hodgkin's disease of the nodular sclerosing type and subsequently developed mycosis fungoides. The Hodgkin's disease was treated with radiation therapy and chemotherapy, and the patient was in complete remission. Seven years later mycosis fungoides occurred and rapidly became progressive. Autopsy revealed that the mycosis fungoides involved multiple organs without any evidence of Hodgkin's disease. The possible significance of the association of these two diseases is presented.

Adult↗

Histiocytosis X. Flow cytometric DNA-content and immunohistochemical and ultrastructural analysis.

A 76-year-old man developed a generalized orange-red nodular eruption associated with constitutional symptoms. A biopsy specimen of a nodule revealed an extensive infiltration of histiocytes with relatively abundant cytoplasm and folded nuclei. Electron microscopy showed Langerhans' cell granules, which confirmed the diagnosis of histiocytosis X. Results of immunohistochemical studies revealed a pattern of antigen expression usually found in histiocytosis X, including Ia, T6, and S100. Analysis of the DNA content of the cells with flow cytometry revealed an aneuploid peak. The patient responded partially to topical mechlorethamine hydrochloride therapy.

Adult↗

Phenotypic analysis in diffuse, large cell lymphoma. Clinical and histologic associations.

To investigate the possible relationships between immunologic phenotype, histologic subtype, and clinical features in diffuse, large cell lymphoma (DLCL), a computerized registry has been established for the prospective collection of immunologic, histologic, and clinical data. A combination of immunofluorescence and immunoperoxidase technics on single-cell suspensions, frozen tissues, and B5-fixed, paraffin-embedded specimens was used to study the first 33 biopsies. A definitive phenotype was established in all but two cases. Monoclonal antibody reagents reactive in B5-fixed, paraffin-embedded tissue sections helped assign a B-cell lineage in four cases lacking surface or cytoplasmic immunoglobulin, monoclonal light chains, and T-cell markers. There was no statistically significant association between the immunologic phenotype (whether mature B or not) and any clinical or histologic parameter, including response to therapy and survival. Bone marrow involvement was found to be associated significantly with both vague nodularity and a cleaved cell subtype. Through the use of a multifaceted approach to the immunophenotypic analysis of the DLCLs, a distinct lineage and stage of differentiation could be assigned to most biopsy specimens. That such analysis has significant clinical implications for patients with DLCL could not be demonstrated in this series.

Adult↗

Cat scratch disease. Identification of bacteria in seven cases of lymphadenitis.

A retrospective study of lymph node biopsy specimens from nine patients with the clinical findings and histologic features of cat scratch disease was undertaken to determine whether the recent report by Wear et al. that pleomorphic bacteria are present in the lymph nodes of cat scratch disease could be confirmed. In seven of our nine cases, pleomorphic bacteria were demonstrated with the Warthin-Starry (WS) silver stain. These were gram-negative with the Brown-Hopps tissue Gram stain and were almost at the limit of microscopic resolution. Lymph node specimens from 13 additional patients with nonspecific lymphadenitis who had neither clinical nor histologic findings of cat scratch disease were studied similarly; in none of these were bacteria demonstrated with the WS silver stain. After examining the distribution of the organisms and the related morphologic features in cat scratch disease, we conclude that demonstration of pleomorphic, gram-negative, WS-positive bacteria in the appropriate clinical and histologic setting can firmly establish the diagnosis of cat scratch disease.

Adult↗

Evaluation of computed tomography and radionuclide scanning in the staging of cutaneous T-cell lymphoma.

Computed tomography (CT) of the abdomen and pelvis was performed on 30 patients with cutaneous T-cell lymphoma (CTCL) as part of their pretreatment staging evaluation. Twenty-two patients also had liver-spleen radionuclide scans. Physical examination revealed limited cutaneous plaque disease in five patients, extensive plaque disease in 11 patients, cutaneous tumors in six patients, and exfoliative erythroderma in eight patients. Generalized palpable adenopathy was detected in 11 patients, localized palpable adenopathy in ten patients, and no adenopathy in nine patients. Peripheral lymph node biopsy specimens showed CTCL in seven patients and dermatopathic lymphadenitis or sinus histiocytosis in 17 patients. Two patients were at disease stage Ia, five were at stage Ib, seven were at stage IIa, two were at stage IIb, seven were at stage III, and seven were at stage IVa. The CT did not reveal intra-abdominal, retroperitoneal, or pelvic adenopathy, or hepatic or splenic abnormalities in any patient. Radionuclide scans demonstrated nonspecific abnormalities in five patients, but did not appear to reflect disease involvement. Computed tomography of the abdomen and liver-spleen radionuclide scans should not be routine staging procedures for CTCL.

Humans↗

Prognostic implications of ploidy and proliferative activity in diffuse large cell lymphomas.

Paraffin-embedded surgical biopsies from 50 patients with newly diagnosed diffuse large cell lymphoma (DLCL) were examined for proliferative activity and DNA aneuploidy by flow cytometry. These results were correlated with the clinical characteristics of these patients and the course of their disease. High proliferative activity, defined as less than 80% of cells in G0 or G1, was found to be the single most important pretreatment adverse prognostic factor in these patients. This relationship remained significant after correcting for poor performance status and advanced Ann Arbor stage, the other factors found to be associated with a shortened survival. DLCLs with high proliferative activity were more probable to present with extranodal involvement than those with lower proliferative activity. The mitotic count as determined by light microscopy did not correlate with flow cytometry-defined proliferative activity and may be a less accurate method for assessing this important biological characteristic in DLCL. DNA aneuploidy was detected in 62% of cases but did not appear to have any prognostic significance. Biopsies from patients who presented with lymphomatous bone marrow involvement, however, invariably demonstrated an aneuploid stemline. These results suggest that differences in proliferative activity may be an important biological basis for the variable prognosis seen in DLCL.

Adolescent↗

Low-dose cytosine arabinoside (Ara-C) therapy in the myelodysplastic syndromes and acute leukemia.

Twenty-two patients with either a myelodysplastic syndrome or acute nonlymphocytic leukemia were treated with 10-21 days of subcutaneous cytosine arabinoside (Ara-C) (5-10 mg/m2 every 12 hours). There were two complete remissions and ten partial responses. Clinically significant improvements in peripheral blood counts persisted for periods of 8 weeks to greater than 21 weeks. Responses were seen even in patients who had previously proven refractory to conventional induction regimens or high-dose Ara-C. The toxicity, however, was considerable. Nearly all patients developed significant thrombocytopenia. Platelet and red cell transfusion support was required in many cases. The response to low-dose Ara-C therapy seen in patients with the leukemic and myelodysplastic disorders may be mediated by the induction of cell differentiation or a direct cytotoxic effect on a sensitive population of cells. Low-dose Ara-C may provide an alternative therapy in the selected patient with acute nonlymphocytic leukemia or a myelodysplastic syndrome.

Acute Disease↗

Use of novel chemical supplements in the establishment of three human malignant lymphoma cell lines (NU-DHL-1, NU-DUL-1, and NU-AMB-1) with chromosome 14 translocations.

Three new cell lines have been established from patients with malignant lymphoma utilizing a human diploid feeder layer, pooled human serum, and the chemical supplements L-cysteine, iron-saturated transferrin, and bathocuproine disulfonate, a copper chelator. After a short period of growth, the 3 cell lines were successfully weaned from the feeder layers but continued to require human serum and the chemical supplements for up to 9 months of culture. The cell lines are currently grown in RPM1-1640 medium and fetal calf serum without further supplementation. The NU-DHL-1 cell line was established from the involved lymph node of a 73-year-old White male with diffuse large-cell lymphoma. The cell line expresses cytoplasmic IgM/lambda heavy and light chains, is Epstein-Barr virus (EBV)-negative, and is positive for several B-cell markers, indicating that it is derived from a mature-B-cell neoplasm. The NU-DUL-1 cell line was established from the cerebrospinal fluid of a 42-year-old White male with undifferentiated lymphoma, non-Burkitt's type, who initially presented with a mediastinal mass and had subsequent involvement of the central nervous system. The cell line is EBV-negative, but surprisingly it is positive for early B-cell markers. The NU-AmB-1 cell line was established from the abdominal mass of a 12-year-old Hispanic male with undifferentiated lymphoma, Burkitt's type. The cell line is EBV-positive and expresses early B-cell markers. All 3 cell lines are aneuploid or pseudodiploid and contain chromosome 14q+ abnormalities including a newly described complex translocation t(?;1;8;14) in the NU-AmB-1 cell line. The establishment of these cell lines was made possible by refinements in the cell culture of the human malignant lymphomas. The availability of well-characterized lymphoma cell lines with specific chromosomal translocations will aid molecular and cellular studies designed to identify the biological significance of genomic rearrangements.

Cell Line↗

Fatal panniculitis.

The Weber-Christian syndrome (relapsing nodular panniculitis) displays a clinical spectrum varying from short, self-limited, or intermittent disease episodes to persistent disease with fatal outcome. Inflamed adipose tissue is exclusively subcutaneous in some patients and is both subcutaneous and perivisceral in others. Inflammation of fat may induce a focal cutaneous or a systemic extracutaneous histiocytic proliferative response in which hemophagocytosis may be a frequent characteristic. Major causes of death--sepsis, hepatic failure, hemorrhage, and thrombosis--are identical in the patients with and without the systemic histiocytic proliferation. Inflammation in fat, of and by itself, may be associated with significant morbidity and mortality, regardless of specific histopathology or inciting factors.

Adolescent↗

Panniculitis associated with cutaneous T-cell lymphoma and cytophagocytic histiocytosis.

A 36-year-old woman had a 6-year history of recurrent panniculitis with development of an angiocentric and angiodestructive cutaneous T-cell lymphoma (CTCL) of the helper cell phenotype. She subsequently developed a rapidly progressive fatal syndrome characterized by cytophagocytic histiocytosis and hyperlipidaemia. Cytophagocytic histiocytosis has previously been reported in association with panniculitis, malignancy and infection, but not with CTCL and the precise relationship between panniculitis, CTCL, cytophagocytic histiocytosis and hyperlipidemia is unclear.

Adult↗

Immunohistochemical analysis of human lymphomas with monoclonal antibodies to B cell and Ia antigens reactive in paraffin sections.

Monoclonal antibodies (MoAbs) to B cell- and T cell-specific antigens uniformly have been restricted in their use to cell suspension or frozen section techniques because the antigens that they identify are either masked or lost in the fixation or paraffin-embedding processes. Antiimmunoglobulin antisera, although readily identifying cytoplasmic immunoglobulin in paraffin sections, has not been as useful as originally hoped since the majority of B cell lymphomas express surface immunoglobulins, which requires cell suspensions or frozen sections for detection. Because cell suspension procedures disrupt tissue architecture and frozen section techniques grossly distort morphology, neither method allows the combination of optimal morphologic and immunologic classification of lymphomas. We recently reported two MoAbs, LN-1 and LN-2, that react with B cells in paraffin sections. LN-1 reacts with the surface membrane and cytoplasm of germinal center B cells. LN-2 reacts uniquely with the nuclear membrane and cytoplasm of mantle zone and germinal center B cells and interdigitating histiocytes. We have also identified a new MoAb, LN-3, that reacts with the HLA-DR antigen in paraffin sections. We now report the use of LN-1, LN-2, and LN-3 in the analysis of paraffin sections from 58 non-Hodgkin's lymphomas and 15 cases of Hodgkin's disease. The types of cells reactive with these MoAbs in neoplastic lymphoid proliferations largely recapitulate their benign morphologic and immunologic counterparts. As a panel, LN-1, LN-2, and LN-3 were reactive with 98% of B cell lymphomas, and LN-1 and LN-2 were negative on all T cell lymphomas. In addition to identifying the cell of origin of these malignant proliferations, these MoAbs were also useful for identifying architectural features in neoplastic lymph nodes. Thus, these reagents provide the ability to assess the immunologic phenotype of neoplastic lymphocytes in conjunction with the critical morphologic criteria requiring paraffin embedding.

Antibodies, Monoclonal↗

Primary cutaneous T-cell lymphoma in a child.

Primary cutaneous lymphoma in childhood is extremely rare. An 11-year-old girl had lesions that were treated as infected insect bites until a biopsy was performed and the diagnosis of primary T-cell lymphoma was made. In contrast to the typically indolent course of cutaneous T-cell lymphoma in adults, the condition in children tends to disseminate rapidly.

Adolescent↗

Angioimmunoblastic lymphadenopathy: clinical and radiological features.

The authors describe the clinical and radiographic features in 7 patients with angioimmunoblastic lymphadenopathy (AIL) with dysproteinemia. This condition should be considered in any patient over 50 who presents with constitutional symptoms such as fever, weight loss, and malaise accompanied by involvement of the peripheral and hilar or mediastinal lymph nodes. Contrary to previous reports, the anterior mediastinal nodes may be involved. Intrapulmonary masses accompanied by clinical deterioration may indicate transformation to immunoblastic lymphoma. The gallium scans and radiographic appearance assist in the diagnosis, but lymph node biopsy is necessary in order to distinguish AIL from lymphoma.

Aged↗