Biomedical subjects
Publications and source records attributed to R A Rudders.
The surface marker classification of non-Hodgkin's lymphomas has demonstrated its value in refining existing morphologic systems of classification and thus in guiding clinical decisions in otherwise ambiguous cases. This accomplishment, in itself significant, may provide the key to the development of effective monospecific therapeutic agents that could be directed at target cells.
We have compared and contrasted the binding of Agg IgM and heavily sensitized EAB (IgM) complexes to the Fc mu receptor of normal and neoplastic human lymphocytes. Agg IgM binds uniformly to the entire SmIg+ B cell population yet normal lymphocytes require culture in order to achieve binding of EAB complexes to a subset of SmIg+ B cells. In blocking studies IgM complexes and IgM aggregates appear to detect the same receptor and with both reagents binding is influenced by the presence of Mg2+ but not Ca2+ and is inhibited by EDTA. The percentage of cells binding EAB was highest in normal B lymphocyte fractions enriched for C2+ cells (CRL+). EAB binding to cells in the CRL- fractions was negligible even though CRL- fractions contained cells which were SmIg+C-3. EAB bound only to neoplastic chronic lymphocytic leukemia cells (CLL) that expressed a high percentage of C+3 cells. Clones lacking a C3 receptor failed to bind EAB. Thus, the binding of EAB complexes to B lymphocytes appears to be associated principally with a subset that express a C3 receptor whereas IgM aggregates bind to the entire SmIg+ B cell population.
We report a case of infectious mononucleosis progressing to fatal immunoblastic lymphoma. The patient, a 44-year-old man who may have had an immunoregulatory defect, failed to have an appropriate T-cell response to his Epstein-Barr (EB) viral infection. His active EB viral infection was manifest by seroconversion of IgM-viral capsid antibody and a greater than four fold rise in IgG-viral capsid antibody. Also, he transmitted his EB viral infection to his wife who became ill 1 month after his death. Clinically the patient's illness was characterized by waxing and waning lymphadenopathy, persistent fever, diarrhea (similar to that associated with cholera), a coagulopathy, and gastrointestinal bleeding. The patient had pathologic findings of a diffuse immunoblastic lymphoma involving lymph nodes, small bowel, liver, pancreas, kidneys, lungs, and bone marrow. Immunologic cell markers showed the tumor to be polyclonal.
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Lymphocytes from normal peripheral blood and human lymphoid tumours were studied for AggIgD binding. In normal blood, 2.0-3.7% of lymphoid cells bound to IgD aggregates. Using double labelling and, enrichment and depletion experiments, a subset of normal B but not T lymphocytes exhibited IgD binding. In blocking experiments, AggIgD binding was shown to be specific and Fc dependent. Likewise, B but not T derived neoplastic lymphoid clones expressed Fc delta receptors. Fc delta receptors were exclusively present on neoplastic clones that also expressed SmIgD. Neoplastic lymphoid cells expressing SmIgM alone did not express Fc delta. The chronic lymphocytic leukaemia cell which typically bore membrane SmIgM and SmIgD expressed multiple FcR with specificities for IgM, IgD and IgG. In sequential surface redistribution experiments, Fc delta and Fc mu receptor-ligand binding produced the 'co-capping' phenomenon which was bidirectional in nature suggesting membrane association.
Between 1976 and 1980, 143 cases of non-Hodgkin's lymphoma have been prospectively analyzed for correlations between surface marker phenotype, histomorphology, and prognosis. This study analyzed 44 adults with tumors classified by Lukes-Collins criteria as small cleaved follicular center cell lymphomas. Two surface marker phenotypic subsets were membrane immunoglobulin, immunoglobulin D (IgD), or a receptor for the third component of the complement system (C'3) (Group I = IgD+ and/or C'3+, group II = IgD-C'3-). Eleven of the 44 patients have died with a projected median survival of 58 months. Four patients in Group I have died with a median survival of 58 months while seven patients in Group II have died with a median survival of 30 months. The difference in the survival curves for the two subgroups is statistically significant (p = 0.01). An analysis of variables such as stage, age, sex, and sites of involvement revealed no differences between the two groups. When classified histologically, the two groups were morphologically indistinguishable and had similar distributions of nodular (follicular) and diffuse variants. Of interest, five patients in Group I were judged to require no initial therapy whereas none in Group II remained untreated initially. The expression of the second heavy chain delta and/or a receptor for C'3 appears to define a subgroup of small cleaved follicular center cell lymphomas with an indolent course and an excellent prognosis.
Since 1974, a group of consecutive adult patients with non-Hodgkin's lymphoma have been prospectively analyzed for tumor-surface membrane-marker phenotype and histopathologic correlation with response to treatment and survival. The results are reported in a subset of 35 patients with advanced (Stages III-IV) large-cell variants, most of whom would be classified by Rappaport criteria as histiocytic. An attempt has been made to define those marker characteristics that will identify long-term survivors in this diverse group who remain in continuous disease-free remission. There were ten patients with complete remissions with intensive treatment. The most common subgroup within the complete responders were patients with cells that were nonexpressive (null) and were classified by Lukes-Collins criteria as the large, noncleaved follicular center cell variant. Currently there are seven patients remaining in complete remission, five of whom have been in continuous disease-free remission for more than two years (total survival 34+-42+ months) following cessation of all treatment. Of those five, four were in the null group and four were classified as large non-cleaved. The actuarial survival curve for all null patients is characterized by a rapid initial decline and a subsequent plateau, which contains four of the long survivors. In contrast, the B-derived group has a more graded decline in survival with time; this curve currently contains the remaining long survivor. Although the overall prognosis of B-derived tumors appears to be superior to that of the null subset, the subgroup with the potential for cure at this point in our study includes patients with both null and B-derived tumors, particularly those classified by Lukes-Collins criteria as the large noncleaved follicular center cell variant.
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This report describes a patient with acute airways obstruction and respiratory failure secondary to a large endotracheal metastasis from a primary ovarian carcinoma first detected seven years previously. Associated airflow obstruction due to mucus impaction contributed significantly to the development of respiratory failure. The tumor responded to radiotherapy, and radiologic evidence for tracheal obstruction was no longer present five months after irradiation.
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In this study we have analyzed a group of 86 consecutive previously untreated patients with nodular lymphoma in order to determine those factors which adversely effect survival. Sixty-two percent of these patients are still living; 23 patients for greater than 36 months. In contrast, 38% have died; 28% of them within 24 months of diagnosis. Striking correlations with short survival were seen with histiocytic cell type, Ann Arbor B symptoms and advanced age. Survival also declined with advanced stage but was A or B symptom dependent. The group was further subdivided into those with exclusively nodular and those with mixed nodular and diffuse histology in order to determine whether the presence of a diffuse component had a negative influence. No significant differences were found in survival patterns between these 2 groups. Our results clearly define a subgroup of nodular lymphoma patients with a poor prognosis which is likely to benefit most from aggressive treatment. The remaining patients are surviving for longer periods of time (albeit many not disease free) and the appropriate treatment for this group remains controversial.
The cumulative 10 year lymphoma experience of a teaching hospital and two of its affiliated institutions was reviewed. From this group, a series of 39 cases of regionally localized primary extranodal lymphomas (Ann Arbor Stages IE and IIE) were selected for study. This group of patients was analyzed for response to initial curative treatment and factors influencing prognosis. The disease-free survival rate following initial treatment is 41% and the rate is 51% if those treated for a single relapse are included. Factors which clearly influence prognosis in this group are stage (extent of disease) at presentation and Rappaport histologic subclassification. The relationships of anatomic site and age to prognosis independent of other factors are unclear. There appears to be an association between sites of involvement in Waldeyer's Ring and the gastrointestinal tract seen both initially and in sites of relapse. An analysis of relapse patterns revealed that 33% of relapses occur as solitary extranodal "skip" recurrences that when treated with radical local treatment may result in long disease-free survival. The latter is one of several findings which suggest that a modification of the current Ann Arbor staging system may be necessary to encompass certain unique features of this group of tumors.
The immunologic surface markers on lymphocytes and clinical characteristics of 35 patients with established (stages 0-4) CLL with absolute lymphocyte counts greater than 15,000/cu mm were compared to those of a group of 25 patients with CLL in an early or preleukemic phase (counts of less than 15,000/cu mm). We found a monoclonal B cell proliferation in most cases in the latter group, in spite of the paucity of clinical and laboratory findings. Furthermore, early CLL can readily be distinguished from benign lymphocytosis by surface marker criteria. In untreated CLL, surface marker characteristics are stable with time and predominantly reflect expansion of clones expressing only B cell markers; however, small increase of blood T cells are often seen. Surface markers are a simple and clinically useful tool for definding and characterizing the preleukemic phase of CLL and its ultimate progression to established CLL.
Chronic lymphocytic leukemia and multiple myeloma in a single individual is a rare occurrence; In previously reported cases, data relevant to the cional relationship between the two entities is not available. In this case, to our knowledge, the tenth reported, immunologic studies indicate that a chance association of two independent diseases has occurred rather than expansion of one single clone of Bcells at two morphological levels.
The usefulness of gallium-67-citrate scanning and lymphangiography in the detection of iliac and paraaortic lymph node involvement was evaluated in 53 patients with Hodgkin's disease and non-Hodgkin's lymphomas who subsequently underwent laparotomy. Our data suggest that the overall accuracies of the two procedures in this regard are comparable. Although in this anatomic area the gallium scan tends to underestimate the presence of disease (higher false-negative rate), the false-negative rate is quite low. The false-negative rate with lymphangiography is lower than with scanning but it tends to overestimate the presence of disease (higher false-positive rate). It was concluded that gallium scanning should be an integral part of the staging of lymphomas and a schema for their clinical staging based on the use of gallium scanning early in the diagnostic sequence is proposed.
A case of typical immunoblastic lymphadenopathy is described. Cell surface marker studies were performed on mononuclear isolates from peripheral blood, ascitic fluid and a lymph node biopsy and the results correlated with light microscopic findings. These data indicated that the majority of the cells in the lymph node were of T cell origin. A smaller percentage of cells could be recognized as deriving from the B cell line and it may have contained a monoclonal subpopulation. Some immunoblasts formed E rosettes and could be identified as T cells but most did not form E or EAC rosettes or bear SmIg and could not be identified as B cells. There was an associated marked increase in mononuclear phagocytes in both ascites and peripheral blood. This disease entity may represent a dual proliferation of cells originating from both B and T cell compartments with T cells predominating in the lymph node in this case.
The clinical records and imaging studies of 140 patients who had 57Co-bleomycin scans were reviewed. In 53% of the patients with known tumor at the time of examination, all clinically demonstrable lesions picked up cobalt. The success rate was particularly high in carcinoma of the lung (15 of 17) and gastrointestinal tract (12 of 17). The major role of cobalt bleomycin seems to be as an early screening test for metastases in patients with carcinoma of the lung, gastrointestinal tract, and uterus. The scan is most useful in demonstrating spread to the brain, liver, and adrenals.
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