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Biomedical subjects

D Variakojis

Publications and source records attributed to D Variakojis.

At least 73 records · Page 4Linked to original sources
PubMed1984

Phenotypic analysis of established diffuse histiocytic lymphoma cell lines utilizing monoclonal antibodies and cytochemical techniques.

Ten diffuse histiocytic lymphoma (DHL) cell lines were extensively characterized with monoclonal antibodies and histochemical techniques. The original biopsy specimens, representing nine of ten cases from which the cell lines were derived, were reviewed utilizing the International Working Formulation. Eight of ten cell lines reacted with anti-immunoglobulin reagents and/or a subset of B-lymphocyte surface markers, supporting a B-cell derivation. Only U-937, a monocytoid DHL cell line reactive with OKT4 and 6, displayed any T-cell markers. Cytochemical analysis alone proved to be of little value in the subclassification of the DHLs. The pathologic review revealed that, despite disparate immunologic phenotypes, five of the diffuse large cell lymphomas were subclassified as large, noncleaved lymphomas. Our analysis confirms the phenotypic diversity of this subgroup of malignant lymphomas and underscores the value of monoclonal reagents for the immunologic evaluation of the hematologic malignancies. These well characterized cell lines constitute a valuable resource for the laboratory investigation of the lymphomas.

Adult↗
PubMed1984

Cytogenetic studies on patients with chronic T cell leukemia/lymphoma.

Cytogenetic studies were performed on three patients with chronic T cell leukemia and on one patient with T cell lymphoma. One of the patients had leukemic cells derived from a suppressor T cell clone, another expressed OKT3, 4, and 8, and cells of the other two were derived from a helper T cell clone. All patients had an abnormal karyotype in peripheral blood or bone marrow cultured with or without mitogen. Modal chromosome numbers were 42 and 44/45 in one patient each and 47 in the 2 others. The structural and numerical abnormalities involved almost all chromosomes, except no. 19 and the X chromosome. All patients had a rearrangement of the long arm of no. 14, with a break at band 14q11;3 patients also had a break at 14q32. An inversion of 14q occurred in two patients; a tandem translocation involving both no. 14 chromosomes and a translocation between no. 14 and no. 17 each occurred in one patient. The break in 14q at band q11 in our cases resembles the chromosome change reported in ataxia telangiectasia. This provides added support for the proposal that a 14q rearrangement involving band q11-12, with or without an accompanying break in 14q32, may confer a proliferative advantage on lymphocytes, especially on those of T cell origin.

Aged↗
PubMed1983

Prognostic implications of karyotype and morphology in patients with non-Hodgkin's lymphoma.

Clonal chromosome abnormalities were observed in 30 patients with non-Hodgkin's lymphoma; the type of lymphoma was characterized on the basis of the International Working Formulation. The 30 patients were classified into five groups according to the chromosome abnormality. There were 8 patients with t(14;18), 3 with t(8;14), 7 with a translocation to the long arm of chromosome 3 (a 3q+ chromosome), 5 with near-tetraploidy, and 7 with other abnormalities. Among the 8 patients with t(14;18), 5 had follicular small cleaved-cell lymphoma (FSC), I had follicular mixed cell lymphoma (FM), and 2 had diffuse large-cell lymphoma (DL); the diagnosis in these 2 patients was based on extranodal tissue. All 3 patients with t(8;14) had DL and B-cell markers. Except for 1 patient, all those with a 3q+ chromosome had DL; 4 of those who were tested had B-cell or pre-B-cell markers. Four of the 5 patients with near-tetraploidy had follicular mixed-cell lymphoma, and 2 of the 7 patients with other abnormalities had T-cell lymphoma. Thus, patients with a t(8;14), a 14q+ chromosome, or a 3q+ chromosome all tend to have diffuse large-cell lymphoma, usually of the non-cleaved type. On the other hand, our data suggest that patients with FSC generally have a t(14;18) whereas those with follicular and diffuse mixed small cleaved cells and large noncleaved cells have a different pattern with modal chromosome numbers in the tetraploid range. We added 17 previously reported patients to the 30 presented here and correlated the karyotype with survival. The 6 patients with near-tetraploidy had the longest median survival, 69 months, the 15 patients with t(14;18) had the next longest, 48 months. The 4 patients with t(8;14) had the shortest survival, 12 months, and the 9 with other abnormalities had the next shortest, 17 months. Intermediate survivals of 27 and 30 months were observed in patients with a 14q+ or a 3q+ chromosome, respectively. The median survival of these various categories differs and our data, thus, indicate that the karyotypic pattern of the malignant cell may be a significant independent prognostic feature influencing the survival of patients with non-Hodgkin's lymphoma.

Adult↗
PubMed1983

Clinical and pathologic cutaneous manifestations of malignant histiocytosis.

The clinical and pathologic changes in the skin of five patients with malignant histiocytosis were studied. The clinical signs included papules, nodules, noduloulcers and purpura. The histopathologic changes included exocytosis of inflammatory cells, infiltration of the papillary and reticular dermis with neoplastic histiocytes, and periadnexal and perivascular infiltrates. Phagocytosis of RBCs and nuclear debris by atypical histiocytes was seen in two cases. In one case, the skin lesions were the only initial manifestation of the disease. Skin involvement occurs in about 10% to 15% of all cases of malignant histiocytosis. Hence, it is important to include malignant histiocytosis in the differential diagnosis of patients with such skin lesions, especially when clinical symptoms may be suggestive of this disease.

Adolescent↗
PubMed1982

Lymphoblastic lymphoma: cytogenetic, pathologic, and immunologic studies.

Cytogenetic, pathologic, and immunologic studies were done on 10 patients with lymphoblastic lymphoma (LL). The median age was 21 years, and males predominated in a ratio of 9:1. At the time of diagnosis, 6 of the 10 patients had an anterior mediastinal mass, 3 had bone marrow involvement, and 2 had central nervous system involvement. All patients were treated with intensive combination chemotherapy. The median survival of the 8 patients who died (7 of whom were adults) was 10.5 months; all 8 achieved only a partial remission. Two other patients were children; they continue in complete remission. Immunologic marker studies were done on 9 of the patients; 5 had T-cell LL, and the other 4 had non-T, non-B LL. In a study of T-cell subpopulations with the use of monoclonal antibodies, the malignant T cells of the 2 patients tested appeared to be mature thymocytes. Clonal chromosome abnormalities were seen in involved tissues from 8 patients; the other 2 patients had a normal karyotype. A 9q+ chromosome, a 6q- chromosome, and a 1q-chromosome associated with 1q trisomy were each seen in 2 patients. No patients had a 14q+ chromosome, which is the most common abnormality in various lymphoproliferative disorders, including other T-cell malignant diseases. The variable chromosome pattern in LL could be related to the heterogeneity of the immunologic phenotype of the malignant T cells. More data are needed before it can be established whether there are any correlations between a particular karyotype and the immunologic phenotype of LL cells.

Adolescent↗
PubMed1982

The treatment of lymphoblastic lymphoma with antithymocyte globulin.

A 20-year-old man with previously treated lymphoblastic lymphoma, a known T-cell disorder, developed progressive disease despite intensive combination chemotherapy with doxorubicin, vincristine, and prednisone. He was subsequently treated with a 21-day course of intravenous antithymocyte globulin at a dose of approximately 15mg/kg per day. This resulted in a marked reduction in lymphadenopathy as determined by physical examination and chest x-ray. Toxicity was limited to minor pruritus which resolved with diphenyldramine and hydrocortisone premedication.

Adult↗
PubMed1982

The effect of short-term and chronic immunosuppression on Theiler's virus demyelination.

Theiler's virus (TV)-infected mice were treated with antithymocyte serum (ATS), cyclophosphamide or pepstatin (a protease inhibitor) to determine the effect on demyelination. When ATS and cyclophosphamide were begun at the time of infection there was significantly less demyelination at 2.5-3.5 weeks than in pepstatin or non-treated infected controls. When immunosuppression was continued for 5 weeks, or when it was not started until 5 weeks post-infection, no significant decrease in demyelination was seen compared to controls. The findings indicate that timing of immunosuppression is critical in determining the extent of TV demyelination. Such demyelination may occur by different mechanisms that are active at different times. The "bystander effect' may be important in early demyelination, but late demyelination may be due to other causes, such as oligodendrocyte lytic infection.

Animals↗
PubMed1982

Reactive lymph node hyperplasia with giant follicles.

Twenty-two cases are presented of patients whose solitary painless, enlarged lymph nodes demonstrated an extreme degree of reactive hyperplasia with giant follicles which were misdiagnosed as lymphoma in 11 (50%) instances. Parotid or submandibular nodes were involved most frequently, and the mass was thought clinically to be a salivary gland tumor in at least one-third of the cases. Occurrence in men predominated (6.3:1) with a median age of 24.5 years (mean, 26.8 years). There were no recurrences during follow-up periods which ranged from 6 months to 15 years. No specific etiologic factors were identified. Microscopically, the enlarged giant follicles involved the entire surface area of the lymph node, frequently assuming a serpentine configuration resulting from coalescence. The description of findings in these exemplary cases is followed by discussion of the histologic differential diagnosis.

Adolescent↗
PubMed1982

Nonrandom chromosome abnormalities in angioimmunoblastic lymphadenopathy.

Cytogenetic and pathologic studies were performed on six patients with angioimmunoblastic lymphadenopathy (AILD). All six had diffuse lymphadenopathy; five had fever, four had weight loss, and four had a diffuse erythematous rash. All patients except one had a polyclonal elevation of immunoglobulin. All patients had diagnostic findings in lymph node (LN) and bone marrow (BM) biopsies. Two patients died of progressive AILD; one patient died after transformation of AILC to immunoblastic sarcoma (IBS); one patient died of gastrointestinal bleeding of unknown cause. The remaining two patients, who have achieved complete remission with intensive chemotherapy, are alive 20 and 8 mo after the diagnosis; one of these had AILD and the other, both AILD and IBS. Despite diagnostic BM biopsy findings, none of the patients had chromosome abnormalities in their BM cells. In studying LN cels of 5 patients, however, we found chromosome abnormalities in each; clonal abnormalities were detected in two, both clonal and nonclonal abnormalities in two, and only nonclonal single-cell abnormalities in one. An extra chromosome 3, seen in four patients, was clonal in two and nonclonal in the two others. Cells with +5, +15, +19, +21, +22 were seen in two patients. All patients had 50% or more normal dividing cells in their LN. The mosaicism of unrelated abnormal cells in their LN. The mosaicism of unrelated abnormal karyotypes that was seen in four patients suggests that this malignant tumor is not necessarily monoclonal in its early stages, but that one clone may be selected and predominate in the late stage. Because nonrandom acquired clonal chromosome abnormalities are a consistent feature of malignancies, our data suggest that AILD may be a malignant disease despite its original description as a benign proliferative process. Therefore, it may require aggressive chemotherapy.

Aged↗
PubMed1982

Correlation of karyotype with clinical features in acute lymphoblastic leukemia.

We studied the clinical and karyotypic features of 50 patients with acute lymphoblastic leukemia, including 33 American and 17 Japanese patients, at two institutions. Clonal chromosome abnormalities were found in 39 of the 50 patients (78%) at diagnosis. Eleven patients had diploidy (N patients). Among the 39 aneuploid patients, 17 had pseudodiploidy (A1 patients), eight had hyperdiploidy with 47 to 49 chromosomes (A2 patients), nine had hyperdiploidy with 50 to 59 chromosomes (A3 patients), and five had other chromosome abnormalities. Of 14 patients whose chromosomes were also studied at relapse, eight had karyotypic progression, five had abnormalities identical or similar to those observed at diagnosis, and one had a change of karyotype from diploidy to aneuploidy. The median age and the median WBC of A1 patients were higher than those of any other group of patients, although one-third of the patients had WBC below 20 x 10(3)/microliters, and they often had leukemic cells of T-cell or B-cell lineage. The A2 patients were relatively old and tended to have higher WBC. The N patients were relatively young and tended to have low WBC, although these tendencies were not as marked as those in A3 patients. The A3 patients had longer survival times than the A1 (p = 0.003) or A2 (p = 0.002) patients. Also, N patients had longer survival times than A1 (p = 0.03) or A2 (p = 0.05) patients. The difference in survival times between A3 and N patients was not significant. Our study demonstrated that the karyotype is correlated with survival and with other recognized prognostic factors. However, in some A1 and A2 patients, the karyotype was a more reliable factor in indicating a poor prognosis than was the WBC or age.

Adolescent↗
PubMed1982

Chromosome pattern in childhood acute nonlymphocytic leukemia (ANLL).

We studied the karyotype in 26 children with ANLL, which was diagnosed on the basis of the FAB classification. Clonal chromosome abnormalities were found in 21 of 26 patients. Four patients, including 3 with Down's syndrome, had AML(M1). Nine patients, including 3 with t(8;21), had AML(M2). All 3 patients with APL(M3) had t(15;17). Four patients had AMMOL(M4); 3 of these had a normal karyotype. Six patients had AMOL(M5); 5 and 11q rearrangements, and 3 of these had a break in 11q23. Only one patient had EL(M6), and he had a normal karyotype. One patient with t(11;19), classified as AML(M2) on Wright-Giemsa-stained cells, had a strong alpha-naphthyl acetate esterase reaction, indicating that the leukemic cells had a cytochemical feature characteristic of monocytes. Whereas t(8;21) and t(15;17) are uniquely associated with AML(M2) and APL(M3), respectively, the 11q rearrangements are also seen in AML(M1/M2), although they are more common in AMOL(M5) and AMMOL(M4). The case with t(11;19) suggests that cells with 11q rearrangements and with AML(M1/M2) may have both monocytic and granulocytic features. When we used our data and previous reports on 243 aneuploid patients (169 adults and 74 children) to correlate the chromosome abnormalities with patient age, we found differences in the chromosome pattern seen among various age groups. This suggests that different etiologic factors as well as changes in host susceptibility may influence the development of and the karyotypic pattern in the various types of leukemia. Moreover, the frequency of various chromosome abnormalities in childhood ANLL can provide a baseline for comparison of the frequency of the same abnormality in adults. The karyotypic analysis of childhood ANLL is important not only because of the information that can be obtained about childhood ANLL, but also because the data can provide substantial insight into the etiology of ANLL in adults.

Adolescent↗
PubMed1982

Primary pulmonary Hodgin's disease: a case report.

A case of Hodgkin's disease occurred with pulmonary involvement as the initial feature. The disease was initially seen clinically and roentgenographically as a diffuse pulmonary infiltrate. To our knowledge, the pattern of diffuse pneumonic involvement without intrathoracic lymphadenopathy at presentation has been reported only in one other case. Differentiation of this diffuse pneumonic pattern of primary pulmonary Hodgkin's disease from the more common pattern of a focal mass or infiltrate is important in considering appropriate therapy.

Adolescent↗
PubMed1981

Multiple histologic subtypes of non-Hodgkin's lymphoma: clinical and pathologic features.

Twenty patients with non-Hodgkin's lymphoma (NHL) had different histologic subtypes of NHL in multiple sites or in a single tumor mass either at the time of their initial biopsy and staging (13 patients) or in the course of their disease (seven patients). These 20 cases represent 3.7% of all patients with NHL seen at the University of Chicago between January 1968 and May 1979. The five-year actuarial survival rate for all 20 patients was 68%. For those 13 patients who had multiple histologic subtypes at the initial workup, the five-year survival rate was 45%; for the seven patients who developed a new histologic subtype later in the course of the disease, the five-year survival rate was 85%. In the latter group of patients, however, the initial biopsy specimens demonstrated better prognostic subtypes, and the median survival from the time of diagnosis of a new, less favorable histologic subtype averaged only four months. These findings indicate that the prognosis is related to the least favorable histologic subtype present, unless this is only a minor component of a composite lymphoma or is limited to one extranodal site.

Adult↗
PubMed1981

Lymphoblastic lymphoma in adults.

Clinical and cytogenetic studied were done on 12 patients with lymphoblastic lymphoma. The ages of the patients ranged from 17 to 58 years (median, 24.5 years). Males predominated by a ration of 5:1. Ten of the 12 patients had a mediastinal mass at diagnosis; two thirds of the patients had involvement of the bone marrow (3 of 12 patients initially were in a leukemic phase), and 5 of 12 patients had involvement of the central nervous system (CNS) with lymphoma. In all patients, the malignant cells were characterized by nuclear convolutions. Cytogenetic studies done on four patients showed clonal chromosome abnormalities in two cases. Six of the 12 patients were treated with the combination chemotherapy regimen COPA and received CNS prophylaxis; their survival was slightly longer than that of the other patients, who were treated with a variety of treatment regimens. Two of the 12 patients achieved a complete remission. The median survival of all patients was 11.5 months but was shorter in patients with initial CNS involvement or leukemia. The poor results achieved thus far in the treatment of this disease demand a new therapeutic approach.

Adolescent↗
PubMed1981

Diffuse histiocytic lymphoma with sclerosis: a clinicopathologic entity frequently causing superior venacaval obstruction.

Of 107 patients with diffuse histiocytic lymphoma (DHL) seen at the University of Chicago, 14 (13%) were classified as having moderate to marked sclerosis. Three of the 14 (21%) had predominantly retroperitoneal masses. Fifty percent of our group, however, had bulky disease seen predominantly or exclusively in the mediastinum, and all of these individuals had superior venacaval (SVC) obstruction. Of the seven patients with SVC syndrome, three were in Pathologic Stage IIA, three were in Clinical Stage II, and only one was in Clinical Stage IIIA. No other patients with DHL displayed SVC obstruction or predominantly mediastinal disease. Five of seven patients with SVC syndrome had large cleaved cell histology. In spite of an apparently favorable histopathologic subtype and a tendency to localized involvement, patients with DHL and sclerosis who have bulky or disseminated disease appear to be resistant to megavoltage radiotherapy alone and relatively resistant to combination chemotherapy.

Adult↗