Biomedical subjects

R R Tubbs

Publications and source records attributed to R R Tubbs.

At least 109 records · Page 6Linked to original sources

PubMed1990

Wegener's granulomatosis. Immunomicroscopic and ultrastructural study of four cases.

Four cases of Wegener's granulomatosis involving lung are reported in which immunomicroscopy demonstrated that the parenchymal and vascular infiltrates were composed primarily of T cells and monocytes. No IgG, IgA, IgM, or C3 was identified in pulmonary vessels or alveolar septa. Ultrastructural studies failed to demonstrate dense deposits in alveolar septal capillaries or interstitium. These findings indicate that a cellular immune mechanism is active in these forms of pulmonary vasculitis and that immune complex deposition does not play a role.

Adult↗

PubMed1990

Lymphoproliferative disorders associated with carbamazepine.

Carbamazepine-induced lymphoproliferative disorders are relatively rare. A 32-year-old woman developed cervical lymphadenopathy while taking carbamazepine. Histologic evaluation of the lymph node biopsy specimen demonstrated near-total effacement of the nodal architecture by a population of pleomorphic immunoblasts. The predominant cell population expressed CD3, CD2, CD5, and CD4, while results of testing for CD8 were negative. On the basis of the morphologic and immunohistologic features, a diagnosis of high-grade, non-Hodgkin's lymphoma, T-cell immunoblastic type, was made. Despite the fact that aggressive behavior is usually associated with immunoblastic lymphomas, the patient has done well for 33 months after cessation of carbamazepine in the absence of chemotherapeutic treatment. The clinical features of this patient's illness, therefore, suggest that it is best regarded as a so-called pseudolymphoma.

Adult↗

PubMed1989

Characterization of two cell lines with distinct phenotypes and genotypes established from a patient with renal cell carcinoma.

Two human renal carcinoma cell lines have been established from the same patient. One cell line (CCF-RC1) was obtained from the primary tumor and the second (CCF-RC2) was established from cells of the renal vein effluent of the perfused tumorous kidney. Although they were established from the same patient, the cell lines differed in certain biological properties. They have been passaged up to 50 times in vitro for about two years. Each has an epithelial morphology and exhibits mutilayering. Cell cycle time of CCF-RC1 and CCF-RC2 was 34 and 36 h, respectively. They exhibited anchorage independent growth, and the plating efficiency of CCF-RC2 in soft agar was higher than that of CCF-RC1. Both lines induced tumors in nude mice at the site of s.c. injection closely resembling the original tumor in histological examination. Electron microscopic features of both tumors in nude mice were consistent with epithelial origin. Doubling time of CCF-RC1 and CCF-RC2 in nude mice was 11 and 12 days, respectively. CCF-RC1 and CCF-RC2 have hypotetraploid karyotype and modal numbers of 83 and 73, presenting two and three marker chromosomes, respectively. Immunocytology with commercial monoclonal antibodies against renal carcinoma (URO-3) and cytokeratin (Mac 6) showed positive reactions with both lines, suggesting that these cell lines derived from renal epithelium. A murine monoclonal antibody (2E11) was generated against CCF-RC2 by the hybridoma technique; 2E11 reacted with CCF-RC2, but not with CCF-RC1. These cell lines may provide a useful model for the study of tumor heterogeneity and its relationship to metastasis.

Animals↗

PubMed1989

Immunophenotypic spectrum of plasma cell leukemia.

Four cases of plasma cell leukemia (PCL) are reported that illustrate the variable immunotype of this disorder in contrast with the immunologic profile described for normal B-cell maturation and typical multiple myeloma (MM). Mature B-lymphocytes express B1 antigen (Ag) and surface immunoglobulin (SIg) whereas maturation to the plasma cell stage is accompanied by loss of these immunologic markers and expression of T10 Ag, plasma cell Ag (PCA), and cytoplasmic immunoglobulin (CIg). Plasma cells from patients with MM have previously been found to express the immunophenotype of normal plasma cells. In contrast, none of the four cases reported here express an immunologic profile typical for specific B-cell differentiation stages. Only one of four cases was strongly positive for PCA but additionally expressed B1 Ag and SIg. Of the remaining three cases, all expressed T10 Ag and CIg; two cases also expressed SIg, weak PCA, and B1 Ag. All four cases were monoclonal for lambda light chains and negative for common ALL Ag (CALLA). The variable expression of mature B-cell markers and plasma cell markers demonstrates the immunophenotypic spectrum of PCL; the prognostic significance of this heterogeneity needs to be more closely examined.

Adult↗

PubMed1989

Rheumatoid arthritis complicated by infection with the human immunodeficiency virus and the development of Sjögren's syndrome.

A patient with seropositive rheumatoid arthritis became infected with the human immunodeficiency virus (HIV) through heterosexual transmission. After the primary phase of the HIV infection, persistent lymphadenopathy, leukopenia, and thrombocytopenia developed. Over the ensuing 3 years, the signs and symptoms of inflammatory polyarthritis completely disappeared, and severe Sjögren's syndrome developed. HIV and its associated immune dysfunction may be responsible for these events.

Antigens, CD↗

PubMed1989

Investigation of the clonality of lymphocytes in Hashimoto's thyroiditis using immunoglobulin and T-cell receptor gene probes.

Southern blotting and DNA hybridization were used for the detection of immunoglobulin and T-cell receptor gene rearrangements in thyroid tissue from six patients with Hashimoto's thyroiditis, three patients with B-cell lymphoma complicating Hashimoto's thyroiditis, and two patients with nonspecific lymphocytic thyroiditis. Immunoglobulin gene rearrangements were detected only in patients with histologic evidence of lymphoma. A single T-cell receptor beta-chain gene rearrangement was detected in one of the patients with uncomplicated Hashimoto's thyroiditis. Based on our knowledge of primary thyroid lymphomas, it is highly unlikely that this case represents an early, histologically occult T-cell lymphoma. The uniform lack of immunoglobulin gene rearrangements in Hashimoto's thyroiditis supports the use of genotypic analysis in differentiating between uncomplicated Hashimoto's thyroiditis and non-Hodgkin's lymphoma. The finding of a T-cell receptor gene rearrangement in a case of Hashimoto's thyroiditis suggests that the immune response in this disease occasionally may be clonally restricted.

Adult↗

PubMed1989

Human neoplasm pH and response to radiation therapy: P-31 MR spectroscopy studies in situ.

Thirty-five human neoplasms from various sites and of various histologic types and stages were examined with phosphorus-31 magnetic resonance spectroscopy in situ. The tumors included 13 squamous cell carcinomas of the head and neck (lymph nodes), eight Hodgkin lymphomas, six non-Hodgkin lymphomas, four carcinomas of the breast, one melanoma, one sarcoma, one neuroblastoma, and one mucoepidermoid sarcoma of the salivary glands. Thirty-four of the neoplasms had normal to slightly alkaline pH before irradiation. During fractionated radiation therapy, the pH stayed in a range of from near neutral to alkaline and rose to 7.6-8.0 at several time points of radiation therapy for some tumors. These results suggest that most tumor cells in human neoplasms are well oxygenated and that only a negligible fraction are chronic hypoxic cells. The fluctuating alkaline pH during radiation therapy occurred regardless of the responsiveness of the treated tumors.

Carcinoma, Squamous Cell↗

PubMed1989

Automation of immunohistology.

Despite the introduction of enzyme-based immunohistology in the late 1960s and early 1970s by Nakane and Taylor, both methodologic and interpretative aspects of this important technology remain, in large part, manual and not automated. Similar approaches to the analysis and sorting of cell markers by immunofluorescence have been automated for a decade using flow cytometry. Automation of both procedural and interpretative aspects of immunohistology has been the focus of greater commercial and professional attention in recent years. Automated immunostaining is accorded several advantages, including cost savings, uniformity of slide preparation, and reduction of procedural human errors. Automated interpretation may not be necessary or desirable for all types of preparations, but it is logical for quantitation of estrogen and progesterone receptors, infiltrating immunoregulatory populations in tumors, and many other applications.

Automation↗

PubMed1989

Interlaboratory variability of immunohistochemical stains. Results of the cell markers survey of the College of American Pathologists.

Immunohistochemical techniques have become commonplace adjunctive aids in anatomic pathology. Although much has been written describing modifications of the basic techniques, sensitivity, and specificity of reagents, little has been published regarding the interlaboratory variability in immunostain results on a given test sample. The Cell Markers Survey of the College of American Pathologists was organized to address this question of interlaboratory variability and to disseminate information on the techniques and reagents currently available.

Biomarkers↗

PubMed1989

Immunophenotypic and genotypic characterization of diffuse mixed non-Hodgkin's lymphomas.

Diffuse, mixed small and large cell lymphomas (DML) are a heterogeneous group of non-Hodgkin's lymphomas. There are only a few published immunophenotypic and/or genotypic studies of DML, and they include a small number of cases. It is unclear whether these neoplasms are monoclonal, oligoclonal, or perhaps of dual lineage. Using monoclonal antibodies (UCHL1, MB2, MT1, LN1, LN2, and L26) that are effective in paraffin-embedded, B5-fixed tissue, 13 cases of DML were studied. This method allowed for improved correlation between cell morphology and immunophenotype compared with frozen section immunohistology. In addition, Southern blotting/DNA hybridization was used to identify directly the lineage of the neoplastic cell population. In each case a population of large B lymphocytes was demonstrated by immunohistology. In six of the cases, a single class of immunoglobulin light chains was detected by frozen section immunohistology, cytospin immunocytology, or both supporting the hypothesis that the B lymphocytes are monoclonal. In almost all the cases (12 of 13), the small cell population consisted predominantly of T lymphocytes. Immunoglobulin gene rearrangements were detected in seven cases, but no T cell receptor gene rearrangements were detected. It was concluded that DML are monoclonal lymphomas of B cell lineage with a non-neoplastic T cell component.

Blotting, Southern↗

PubMed1988

T-cell lymphomas containing Epstein-Barr viral DNA in patients with chronic Epstein-Barr virus infections.

Fatal T-cell lymphomas developed in three patients with a chronic illness manifested by fever, pneumonia, dysgammaglobulinemia, hematologic abnormalities, and extraordinarily high titers of antibody to the Epstein-Barr virus (EBV) capsid antigen (greater than 10,000) and early antigen (greater than 640) but low titers to the EBV nuclear antigen (less than or equal to 40). To understand the pathogenesis of these tumors better, we determined the immunophenotype of the tumor cells and analyzed tumor-cell DNA for EBV genomes and for lymphoid-cell gene rearrangements. More than 80 percent of the cells in tumors had an activated helper T-cell phenotype (T4, T11, la positive). The EBV genome was found by in situ hybridization in tumor tissue from each patient. Southern blot assay of DNA digests from one patient showed the same pattern as that of the EBV-infected marmoset line, B95-8. DNA digests from two patients showed a monoclonal proliferation of T cells determined on the basis of uniform T-cell-receptor gene rearrangements and a single band for the joined termini of the EBV genome. We conclude that EBV may infect T cells and contribute to lymphomas in selected patients with severe EBV infections.

Adult↗

PubMed1988

Peripheral small cell undifferentiated carcinoma of the lung. Clinicopathologic features of 17 cases.

Seventeen cases of resectable peripheral small cell undifferentiated carcinoma of the lung were studied (average size, 2.1 cm; range, 0.9-3.5 cm). The carcinomas exhibited predominantly mixed intermediate and fusiform/spindle subtypes; in seven carcinomas there were at least some foci of oat cell subtype. There was no histologic evidence of typical carcinoid tumor. Seven cases were fixed in solutions appropriate for immunohistologic study; these exhibited prominent neuron-specific enolase activity but less prominent and more variable staining for the carcinoembryonic antigen and cytokeratins. All 17 cases were deemed resectable and had no clinical or radiologic evidence of metastasis. Seven (41%) patients died with recurrent and/or metastatic carcinoma (average survival, 1.7 years); five of these patients had carcinomas with at least some foci of oat cell foci subtype.

Adult↗

PubMed1988

Modulation of intestinal immune reactivity by interleukin 2. Phenotypic and functional analysis of lymphokine-activated killer cells from human intestinal mucosa.

There is evidence indicating that interleukin 2 may be important in the regulation of intestinal immunity, as suggested by its capacity to induce nonspecific cytotoxic (lymphokine-activated killer) activity from human intestinal mucosal mononuclear cells. The present study was designed to further explore the phenotypic and functional changes induced by interleukin 2 on intestinal lymphocytes derived from inflammatory bowel disease and control tissues. Immunohistology of intestinal mucosa demonstrated few cells bearing the activation antigen recognized by anti-Tac (anti-interleukin 2 receptor) monoclonal antibody. However, when isolated lamina proprial mononuclear cells were exposed to interleukin 2 in culture, the number of Tac-positive cells increased dramatically, a phenomenon paralleled by the generation of lymphokine-activated killer cell activity. This cytotoxic function was critically dependent on the continuous availability of interleukin 2, but not on the expression of the Tac antigen, since Tac-negative cells were also cytotoxic. Depletion of natural killer cells, fractionation into T cell-enriched and -depleted cells before and after culturing with interleukin 2, and separation into Tac-positive and -negative cells after interleukin 2 activation failed to eliminate lymphokine-activated killer cell activity, suggesting that this phenomenon is mediated by phenotypically and functionally heterogeneous cell subsets. During the induction of lymphokine-activated killer cells variable amounts of interferon-gamma were produced, but these did not correlate with the degree of cytotoxicity. No differences were observed between the response to interleukin 2 by inflammatory bowel disease and control cells. Therefore, in view of its capacity to induce significant phenotypic and functional changes in different subpopulations of intestinal mucosal mononuclear cells, interleukin 2 should be regarded as an important modulator of intestinal immune reactivity.

Adjuvants, Immunologic↗

PubMed1988

Absence of B-cell or T-cell clonal expansion in nodular, lymphocyte predominant Hodgkin's disease.

Recent studies based upon immunophenotypic data have provided strong evidence that nodular lymphocyte predominant Hodgkin's disease (NLPHD) represents an entity that is distinct from other subtypes of Hodgkin's disease (HD). In contract to other forms of HD, the predominance of B-lymphocytes in NLPHD has prompted the thesis that this lesion is actually an atypical B-cell hyperplasia or follicular center cell lymphoma. Three cases of NLPHD by restriction endonuclease analysis were studied in an attempt to identify a clonal B-cell or T-cell expansion in this disorder. DNA was extracted from these tumors and hybridized to probes for the immunoglobulin genes (C kappa, C lambda, JH) and the T-cell receptor beta chain gene. Gene rearrangements were not detectable in any of the cases. The results provide genotypic evidence that there is not a monoclonal or oligoclonal proliferation of small B-lymphocytes or T-lymphocytes in NLPHD. The possibility that the L&H Reed-Sternberg cells are monoclonal cannot be excluded because their small number is below the level of sensitivity of this technique.

Antigens, Differentiation, T-Lymphocyte↗

PubMed1988

Paracortical immunoregulatory subpopulations in lymph nodes from homosexual men with persistent generalized lymphadenopathy.

Homosexual patients with persistent generalized lymphadenopathy usually show an abnormal expansion of paracortical T8+ lymphocytes relative to T4+ cells in lymph nodes with reactive follicular hyperplasia (RFH). This study was designed to characterize further the paracortical lymphocyte population in homosexual men with reactive follicular hyperplasia, because T8+ lymphocytes are antigenically and functionally heterogeneous. Frozen lymph node tissue from 10 patients was evaluated. Monoclonal antibodies to T8, Leu-15, NKH-1, Leu-7, and HLA-DR antigens were employed in the avidin-biotin complex immunoperoxidase technique. With digitized morphometry, positively stained cells for each marker were counted in five 0.145-mm2 microscopic fields. Four tonsils with RFH were used as controls. Most paracortical cells were T8+ (median, 4182 T8+ cells/five fields), and values were significantly higher than those for controls (median, 1518 T8+ cells p less than 0.006). In every case there were markedly fewer Leu 15-, NKH-1, Leu 7-, and HLA-DR-positive cells than T8+ cells (median values per five fields: Leu-15, 144; NKH-1, 12; Leu-7, 3; HLA-DR, 195). Moreover, these values were not significantly different from control values. Our findings suggest that the expanded paracortical T8+ population comprises cells with the immunophenotype of cytotoxic Leu-15-, T8+ lymphocytes, rather than natural killer or Leu-15+, T8+ suppressor cells.

AIDS-Related Complex↗

PubMed1988

Immunoglobulin and T-cell receptor genes in thymomas: genotypic evidence supporting the nonneoplastic nature of the lymphocytic component.

On the basis of morphologic and immunophenotypic studies, it is generally accepted that the lymphocyte population in thymomas is not neoplastic. We studied 10 thymomas with restriction endonuclease and Southern blot/DNA hybridization methods in an attempt to provide genotypic evidence in support of this hypothesis. The clinical, gross, and microscopic features of each case were reviewed and found to be entirely consistent with the diagnosis of thymoma. In addition to conventional histologic methods, we also studied each tumor by immunohistologic techniques. The lymphocytes generally had an immunotype characteristic of immature cortical thymocytes, and the epithelial cells were uniformly stained by antikeratin antibodies. DNA probes for the T-cell receptor beta-chain gene and immunoglobulin genes (C kappa, C lambda, and JH) were used in the genotypic studies. No gene rearrangements were detected in any of the thymomas. This study provides additional evidence that clonal proliferations of T or B lymphocytes are not present in thymomas; therefore, these cells are almost certainly not neoplastic. The results also provide a basis for the effective use of restriction endonuclease and Southern blot/DNA hybridization analysis in the differential diagnosis of non-Hodgkin's lymphoma and thymoma.

Adult↗

PubMed1988

Nephrotic range proteinuria with "minimal change glomerulopathy" in human renal allografts: report of four cases.

Four patients who received renal allografts developed nephrotic range proteinuria 2 to 16 months after renal transplantation. Twenty-four-hour urine protein excretion at the time of renal allograft biopsy ranged from 5.9 to 17.0 g/24 hours. The serum creatinine at the time of renal allograft biopsy ranged from 2.0 to 3.9 mg/dl (180 to 350 mumol/L). Biopsies of the allografts demonstrated minimal glomerular abnormalities by light microscopy, immunomicroscopy, and electron microscopy. Two biopsies exhibited severe interstitial fibrosis. These four cases illustrate the unusual finding of "minimal change glomerulopathy" in renal allograft recipients exhibiting nephrotic range proteinuria. All four patients progressed to dialysis 4, 36, 46, and 53 months after transplantation. Transplant nephrectomy was performed in three patients. One showed acute cortical necrosis. Two showed glomerular, vascular, and tubular-interstitial features of chronic rejection.

Adult↗

PubMed1988

Immunotypic and genotypic characterization of non-Hodgkin's lymphomas of the ovary.

Ovarian non-Hodgkin's lymphomas (NHLs) are rare, and accurate diagnosis is frequently problematic. Previous studies have not provided either complete immunotypic or genotypic analyses. The authors report immunotyping and genotyping of three cases of ovarian NHL, including both primary and secondary types. Immunotyping disclosed all three were B-cell lymphomas composed of secretory blast stage lymphocytes showing kappa immunoglobulin (Ig) light chain clonal excess. DNA extracted from frozen tissue of each tumor was subjected to restriction endonuclease digestion and hybridized to probes for Ig genes, C kappa, C lambda, JH, and the T-cell receptor beta-chain gene. Rearrangements of the heavy chain and light chain Ig genes were observed in all three cases, confirming the monoclonal B-cell origin of the neoplastic population. No detectable rearrangements were observed in DNA extracted from three nonlymphoid ovarian tumors (dysgerminoma, granulosa cell tumor, and fibrothecoma). This study documents the potential value of immunotyping and genotypic analysis in the study of ovarian tumors.

Adult↗