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Biomedical subjects

R R Tubbs

Publications and source records attributed to R R Tubbs.

At least 127 records · Page 7Linked to original sources

Solitary primary lymphoma of the sciatic nerve: case report.

An unusual case of a solitary extranodal primary lymphoma of the sciatic nerve in a patient presenting with sciatica and a left footdrop is described. Magnetic resonance imaging was successful in identifying a fusiform lesion in the sciatic nerve in the left infragluteal region. Surgical exploration and biopsy confirmed this as a B cell lymphoma. An extensive metastatic work-up has not identified other sites of lymphomatous involvement.

Humans↗

Cyclosporin-associated microfibrils in cardiac transplant patients.

Endomyocardial biopsies from 21 cyclosporin-treated cardiac transplant patients were studied at the ultrastructural level. Eight patients exhibited focal interstitial accumulation of filaments, which most commonly measured 8-10 nm in diameter (range 7-16 nm). The filaments were straight, hollow, and nonbranching. Filament accumulation was observed as early as 4 days posttransplant. No filament accumulation was observed in 17 donor endomyocardial biopsies obtained at the time of transplantation. The ultrastructure of the filaments was similar to that of amyloid fibrils. Stains for amyloid at the light microscopic level were uniformly negative, however. Until the exact nature of the filaments is determined, we propose that they be referred to as cyclosporin associated microfibrils.

Actin Cytoskeleton↗

Is hemisplenectomy a satisfactory option to total splenectomy in abdominal staging of Hodgkin's disease?

The spleens removed in 76 consecutive staging laparotomies for Hodgkin's disease were studied. The spleens were divided from superior to inferior pole into anterior and posterior halves and each half further divided into superior, mid, and inferior sectors. Sectors were studied grossly and microscopically and involvement by Hodgkin's recorded. Of the 23 positive spleens, all sectors were positive in 12, 5 sectors positive in 1, 4 sectors in 3, 3 sectors in 3, 2 sectors in 1, and 1 sector in 2. In one spleen, four sectors were involved but were not marked properly to allow identification of which four, and one spleen with fairly diffuse disease was not handled according to protocol, remaining an "indeterminate" positive. From the anatomic distribution, a lower pole hemisplenectomy would have removed disease in 22 of 23 spleens and likely would have shown disease in the diffusely involved "indeterminate" spleen. An upper pole hemisplenectomy would have missed disease in one spleen and possibly in the "indeterminate" spleen. Either approach would have missed disease in around 1% of the 76 cases. The addition of a biopsy of the opposite pole that remains is technically feasible and would reduce this small incidence of undetected abdominal disease. With the increasing appreciation of the importance of the immunologic functions of the spleen, alternative techniques for determining splenic involvement have been proposed. From this study, hemisplenectomy appears to be an attractive alternate that preserves the vital functions of the spleen with a minute risk of overlooking the presence of Hodgkin's disease.

Adolescent↗

The macrophagic origin of multinucleated giant cells in myeloma kidney: an immunohistologic study.

The cast-engulfing giant cells in a case of kappa light chain nephropathy/Bence Jones cast nephropathy were characterized with monoclonal antibodies Uro-5 (renal epithelium: Henle's loop, distal tubule, collecting duct) and Leu-M5 (macrophage/monocyte/dendritic cell specific). The giant cells were Leu-M5 positive and Uro-5 negative. There was an increased concentration of Leu-M5-positive cells surrounding cast-containing tubules, and occasional Leu-M5-positive cells were found within the tubular epithelial layer. Although there were no Uro-5-positive giant cells, an occasional Uro-5-positive cell was found within casts. The majority of casts were found within Uro-5-positive tubules. These results confirm earlier electron microscopic reports that the cell of origin of the cast-engulfing multinucleated giant cell is the macrophage (Leu-M5 positive, Uro-5 negative). These giant cells may originate from macrophages that have migrated from the interstitium through the tubular epithelium.

Antibodies, Monoclonal↗

Chronic glomerular microangiopathy complicating metastatic carcinoma.

Six cases of metastatic carcinoma associated with chronic glomerular microangiopathy and renal failure are reported. All had prominent subendothelial lucent zones and double-contoured glomerular basement membranes. There was no immunohistologic or ultrastructural evidence for immune complex entrapment in glomeruli. By immunohistology, material antigenically related to fibrin or fibrinogen was identified in glomerular basement membranes despite a paucity of typical fibrillar fibrin. Four patients received mitomycin C before the onset of renal disease, and one patient received chemotherapy other than mitomycin C before development of renal failure. One patient had no chemotherapy but was given radiotherapy, which did not include the kidneys in the irradiated field. These six cases emphasize the diverse pathophysiologic mechanisms by which glomerular microangiopathy may arise in metastatic carcinoma.

Adenocarcinoma↗

A double-blind comparative immunotypic study between two institutions phenotyping non-Hodgkin's lymphomas.

To establish the feasibility of immunotyping specimens transported over great distance, the University of Arizona and the Cleveland Clinic exchanged 39 lymphoma cases (26 B-cell, 13 T-cell cases) via air express for phenotyping. They were exchanged with the use of glass slides with adherent snap-frozen sections. The method involved immunohistochemistry using a common battery of 20 antibodies directed at B- and T-cell antigens. Using similar, but not identical, methods and reagents, cases were assayed before and after transport. Results were generated as paired determinations in a double-blind fashion (1,338 total determinations, 669 paired determinations/669 antigens). Using "pretransport" values as the baseline, there was subsequent agreement with baseline in 624 of 669 antigenic determinations (93.3%) and disagreement in 45 (6.7%). Interinstitutional agreement was 94% for T-antigens (Leu-1-7,9) and 93% for B-antigens (K, lambda; IgM, G, A, D; B1, B2, B4, L14; J5, common acute lymphocyte leukemia antigen [CALLA]; Ia). In spite of 6.7% disagreement, there was agreement of overall phenotypic profile (e.g., B vs. T and subset stage) in all 39 cases. This is because discrepancies were isolated and the battery offset undue reliance on a single antigen. The disagreements relate mainly to certain B-antigens: CALLA/J5 (eight disagreements) and B1 and B2 (six and five disagreements, respectively). T-antigen disagreements were more sporadic (e.g., Leu-5 [three disagreements]). These discrepancies may relate to antigen loss with transport, variable antigen density or antibody avidity, methodologic differences, quality of reagents, or differences of phenotype interpretation. A further exchange of the 45 disagreement slides indicated that difference of observer interpretation was a minor factor (3 of 45). In conclusion, the authors' study demonstrates a high degree of immunotype reproducibility (approximately 93%), suggesting promise for institutions doing collaborative lymphoma studies.

Antibodies, Monoclonal↗

Perforating granuloma annulare in a patient with acquired immunodeficiency syndrome. Immunohistologic evaluation of the cellular infiltrate.

The inflammatory infiltrate found in the lesions of perforating granuloma annulare in a patient with acquired immunodeficiency syndrome was analyzed. Double labeling with fluorescent antibody tags fluorescein isothiocyanate-Leu 4 (peripheral T cells) and phycoerythrin-Leu 2a (cytotoxic/suppressor) revealed the infiltrate to consist predominantly of cytotoxic/suppressor T cells. This finding is a reflection of the patient's altered immune status and calls into question the role of specific T-cell subsets in the pathogenesis of granuloma annulare.

Acquired Immunodeficiency Syndrome↗

Lymphocyte nuclear morphology in diffuse well-differentiated lymphocytic lymphoma. Comparative morphometry of normal lymphoid tissues, non-Hodgkin's lymphoma, and Hodgkin's disease.

Precise morphologic data on the relationship of diffuse well-differentiated lymphocytic lymphoma (DWDLL) to other non-Hodgkin's lymphomas (NHLs) are lacking in current classifications of lymphomas. Morphometry of plastic-embedded tissues describes details of the mean nuclear parameters and distribution of lymphocyte-types in 14 cases of DWDLL in nodal and extranodal sites. The results indicate that the proportion of small (unstimulated or nontransformed) lymphocytes in DWDLL varies from 50% to 86%. The mean nuclear area of small lymphocytes in DWDLL is either within the size range or somewhat smaller, and many examples are more irregular in shape, than the small lymphocytes in germinal centers that are morphologically comparable with the majority of lymphocytes in DWDLL and mantle zones. The morphologic relationship of DWDLL to other NHLs, Hodgkin's disease, and paracortical, mantle, and germinal center lymphocytes in lymphoid-reactive hyperplasia was established by morphometric analysis of the nuclear profiles of small lymphocytes. The small (nontransformed) lymphocytes in those subtypes of NHL other than DWDLL have abnormally small and more irregular nuclear profiles than those in normal small lymphocytes, or the small-lymphocyte population of Hodgkin's disease. Such findings may be of diagnostic significance to pathologists.

Biopsy↗

Autoimmune oophoritis: a histopathologic study of involved ovaries with immunologic characterization of the mononuclear cell infiltrate.

The ovaries from a patient with autoimmune oophoritis and premature ovarian failure were extensively evaluated by light microscopy and immunohistochemistry. A marked infiltrate of plasma cells and lymphocytes affected developing, cystic and atretic follicles but spared primordial follicles. Immunotyping of the ovarian mononuclear cell infiltrate revealed a mixture of B cells (including plasma cells) and T cells (both T4+ and T8+), as well as numerous macrophages and a few natural killer cells. These findings suggest that a complex immune process with an interplay of humoral and cellular mechanisms is involved in the pathogenesis of autoimmune oophoritis.

Adult↗

Pulmonary lymphoid neoplasms. Role of immunohistology in the study of cellular immunotypes and in differential diagnosis.

Seven cases of lymphoid neoplasms presenting in the lung were evaluated by immunohistology for T and B cell antigens and immunoglobulin light chains in frozen tissue sections. Although follow-up was short or inconclusive in some patients with lymphoma and pseudolymphoma, it was concluded that evaluation of T and B cell antigens and immunoglobulin light chains in frozen tissue is helpful in classifying lymphocytic neoplasms, especially in cases without definite cytologic evidence of malignancy. As demonstrated in two additional cases, lymphocyte/leukocyte markers in paraffin-embedded tissue are important in the differential diagnosis of lesions with cytologic features of malignancy.

Adult↗

Focal and segmental glomerulosclerosis. Immunohistologic study of 20 renal biopsy specimens.

To evaluate the deposition of immunoglobulins and complement and their relationship to sclerotic and nonsclerotic glomerular segments, immunoperoxidase without periodic acid-Schiff counterstain (IMP) and with periodic acid-Schiff counterstain (IMPAS) for IgG, IgA, IgM, and C3 was performed on cryostat-frozen sections using the direct method, along with routine light microscopy and electron microscopy, in a series of 20 renal biopsy specimens from 20 patients with the final diagnosis of focal and segmental glomerulosclerosis. Neither diffuse mesangial nor diffuse glomerular basement membrane deposits were detected by IMP, IMPAS, or electron microscopy. In 18 biopsy specimens, IMPAS demonstrated focal and segmental granular to globular deposits of IgM and/or C3 in sclerotic glomerular segments. In eight biopsy specimens, small granular deposits of IgM and/or C3 deposits were identified in optically normal glomeruli, suggesting that these deposits may precede segmental sclerosis.

Adolescent↗

Small noncleaved B cell Burkitt-like lymphoma with chromosome t(8;14) translocation and Epstein-Barr virus nuclear-associated antigen in a homosexual man with acquired immune deficiency syndrome.

This case report describes new manifestations of the acquired immune deficiency syndrome (AIDS) in a promiscuous homosexual man. Investigation of upper gastrointestinal bleeding in the patient lead to discovery of a high-grade, small, noncleaved cell (Burkitt-like) gastroduodenal lymphoma with visceral and extralymphatic extension. Specific phenotyping of the lymphoma revealed that it was a monoclonal B cell lymphoma of mu kappa isotype. An in vitro cell line was established that was Epstein-Barr virus nuclear-associated antigen-positive. The lymphoma cells displayed a t(8;14) translocation similar to endemic African Burkitt lymphoma. Epstein-Barr virus genomes were identified in the lymphoma and an axillary lymph node biopsy specimen by molecular hybridization. These data strongly suggest that Epstein-Barr virus actively infected this patient. However, he showed normal Epstein-Barr virus-specific serologic responses, indicating an immune defect against the virus.

Acquired Immunodeficiency Syndrome↗

Human intestinal mucosal mononuclear cells exhibit lymphokine-activated killer cell activity.

Previous investigations have shown that mononuclear cells present in human intestinal mucosa possess cytotoxic properties that are unique and different from those of cells circulating in the peripheral blood. We have further explored the cytolytic capacity of human intestinal mucosal mononuclear cells using both phenotypic and functional criteria. Using an immunoperoxidase technique on gut frozen sections, we failed to identify cells bearing surface markers displayed by natural killer cells and recognized by the monoclonal antibodies Leu7, Leu11, and Leu15. Freshly isolated human lamina proprial mononuclear cells (LPMC) were unable to lyse K562 target cells, even after using a variety of experimental conditions which included depletion of adherent cells, fractionation by Percoll gradients or panning with monoclonal antibodies, and treatment with a prostaglandin synthetase inhibitor or interferon-gamma. In contrast, when LPMC were cultured in the presence of the lymphokine interleukin 2 (IL 2), they displayed high levels of cytotoxicity against both K562 and Daudi target cells. Such cytolytic activity appeared after 1 or 2 days of culture, was dependent on the amount of IL 2 added to the cultures, was independent of plastic adherent cells, and could be inhibited by agents that block proliferation. Interferon-gamma, when used under experimental conditions identical to those adopted for IL 2, was unable to induce any significant cytotoxicity by LPMC or enhance the level of killing obtained by stimulation with IL 2 alone. This IL 2-induced, nonspecific cytotoxicity of LPMC probably represents a form of lymphokine-activated killer cell function similar to that recently described for human peripheral blood lymphocytes. In view of the absence of morphologic and functional evidence for natural killer cells in human intestinal mucosa, the phenomenon of lymphokine-activated killer cell activity displayed by LPMC may represent an alternate cytotoxic function potentially relevant to intestinal mucosa immunity.

Adolescent↗