Biomedical subjects

C W Ross

Publications and source records attributed to C W Ross.

At least 55 records · Page 3Linked to original sources

PubMed1993

Radioimmunotherapy of B-cell lymphoma with [131I]anti-B1 (anti-CD20) antibody.

BACKGROUND: Many patients with non-Hodgkin's lymphomas are not cured by current therapies, and new approaches to treatment are needed. As part of an ongoing phase 1 study, we examined the effect of radioimmunotherapy with 131I-labeled B-cell-specific anti-CD20 monoclonal antibody in 10 patients with CD20-positive B-cell lymphomas in whom primary chemotherapy had failed. METHODS AND RESULTS: Anti-B1 (anti-CD20) mouse monoclonal antibody trace-labeled with 131I (15 mg containing 5 mCi) was given intravenously at approximately one-week intervals: first, without pretreatment with unlabeled anti-B1 antibody, to all 10 patients; then, with pretreatment with 135 mg of unlabeled antibody, to 8 patients; and then, with pretreatment with 685 mg, to 2 patients. Serial quantitative gamma-camera images and measures of whole-body radioactivity were obtained after each tracer dose. All known disease sites larger than 2 cm could be imaged. The effect of a pretreatment dose of unlabeled anti-B1 antibody on targeting of the tumor with the radiolabeled antibody was variable. The pretreatment dose of unlabeled antibody that produced the highest ratio of the tumor dose to the whole-body dose in tracer studies was then used to deliver higher doses of radioactivity for radioimmunotherapy in nine patients. Three patients received doses designed to deliver 25 cGy to the whole body (two patients treated twice, six to eight weeks apart), four patients received 35 cGy (one patient treated twice), and two patients received 45 cGy (one patient treated twice); each dose contained 34 to 66 mCi of activity. Six of the nine treated patients had tumor responses, including patients with bulky or chemotherapy-resistant disease: four patients had complete remissions, and two had partial responses. Three patients had objective responses to tracer infusions before they received radioimmunotherapeutic doses. Of the four patients with complete remissions, one remained in remission for eight months and the other three continue to have no disease progression (for 11, 9, and 8 months). There was mild or no myelosuppression. CONCLUSIONS: Radioimmunotherapy with [131I]anti-B1 antibody is a promising new treatment for lymphoma.

Adult↗

PubMed1993

Leukemic T cells from patients with cutaneous T-cell lymphoma demonstrate enhanced activation through CDw60, CD2, and CD28 relative to activation through the T-cell antigen receptor complex.

Antigen-dependent activation of T cells occurs through the T-cell antigen-receptor complex (TCR/CD3). Antigen-independent T-cell activation may occur through the surface molecules CDw60, CD2, and CD28. We wished to determine whether these antigen-independent T-cell-activation pathways could be involved in proliferation of leukemic T cells from patients with cutaneous T-cell lymphoma (CTCL). Whereas CDw60 was only expressed on 28% +/- 7% (mean +/- SEM) of blood T cells obtained from healthy control subjects (n = 4), CDw60 was expressed on 94% +/- 3% of blood T cells obtained from patients with CTCL (n = 4). Dual color immunofluorescence microscopy of the T-cell infiltrate in involved skin of these patients demonstrated that almost 100% of the T cells expressed CDw60. Not only did T cells in the patients with CTCL express CDw60, but triggering of the T cells with anti-CDw60 resulted in enhanced proliferation relative to anti-TCR/CD3 and mitogenic lectins. Other antigen-independent pathways also appeared highly active in the T cells from patients with CTCL because enhanced proliferation relative to anti-TCR/CD3 or mitogenic lectins was found when anti-CD2 or anti-CD28 plus phorbol ester was used as stimulant. Despite the brisk proliferation induced by anti-CDw60, anti-CD2, or anti-CD28, T cells from the patients did not produce detectable amounts of gamma-interferon. The inability to produce gamma-interferon correlates with our finding of absent (n = 3) or weak (n = 1) intercellular adhesion molecule-1 expression in the lesional keratinocytes in these patients. In conclusion, T cells of patients with CTCL demonstrate elevated expression of a T-cell-independent signaling molecule CDw60 and respond to antigen-independent activating signals.

Aged↗

PubMed1993

Acute biphenotypic leukaemia: immunophenotypic and cytogenetic analysis.

The incidence of acute biphenotypic leukaemia has ranged from less than 1% to almost 50% in various reports in the literature. This wide variability may be attributed to a number of reasons including lack of consistent diagnostic criteria, use of various panels of antibodies, and the failure to recognize the lack of lineage specificity of some of the antibodies used. The morphology, cytochemistry, immunophenotype and cytogenetics of acute biphenotypic leukaemias from our institution were studied. The diagnostic criteria took into consideration the morphology of the analysed cells, light scatter characteristics, and evaluation of antibody fluorescence histograms in determining whether the aberrant marker expression was arising from leukaemic blasts or differentiated bone marrow elements. Fifty-two of 746 cases (7%) fulfilled our criteria for acute biphenotypic leukaemias. These included 30 cases of acute lymphoblastic leukaemia (ALL) expressing myeloid antigens, 21 cases of acute myelogenous leukaemia (AML) expressing lymphoid markers, and one case of ALL expressing both B- and T-cell associated antigens. The acute biphenotypic leukaemia cases consisted of four major immunophenotypic subgroups: CD2+ AML (11), CD19+ AML (8), CD13 and/or CD33+ ALL (24), CD11b+ ALL (5) and others (4). Chromosomal analysis was carried out in 42/52 of the acute biphenotypic leukaemia cases; a clonal abnormality was found in 31 of these 42 cases. This study highlights the problems encountered in the diagnosis of acute biphenotypic leukaemia, some of which may be responsible for the wide variation in the reported incidence of this leukaemia. We suggest that the use of strict, uniform diagnostic criteria may help in establishing a more consistent approach towards diagnosis of this leukaemic entity. We also suggest that biphenotypic leukaemia is comprised of biologically different groups of leukaemia based on immunophenotypic and cytogenetic findings.

Adolescent↗

PubMed1992

CD30 (Ki-1)-positive, anaplastic large cell lymphoma mimicking gastrointestinal carcinoma.

BACKGROUND: There is great diversity in the clinical presentation of CD30 (Ki-1)-positive, anaplastic large cell lymphoma (ALCL). The authors report two patients in whom the clinical and morphologic features mimicked gastrointestinal carcinoma. METHODS: Surgical pathology specimens were examined using standard histologic techniques. Paraffin- and frozen-section immunohistochemistry was performed by an avidin-biotin-peroxidase method. RESULTS: The first patient is a 58-year-old man who presented with a constricting mass of the sigmoid colon. Immunohistochemical staining for CD45 (LCA) was negative in formalin-fixed paraffin sections. However, CD45 and CD74 (LN2) were detectable in B5 postfixed material. The second patient is a 44-year-old woman who presented with dysphagia and back pain. Endoscopic examination revealed an ulcerated luminal mass in the proximal esophagus and a gastric ulcer. Mucosal biopsy specimens of the esophagus and stomach contained ALCL, which was CD45 positive. Retroperitoneal lymph nodes contained ALCL infiltrating the sinuses, interfollicular areas, and blood vessel lumina. In addition to CD45 and pan-T-cell antigens, the neoplastic cells expressed CD68 (KP1) and epithelial membrane antigen (EMA). Monoclonal antikeratins were negative, but a polyclonal antikeratin stain was positive. CONCLUSIONS: These findings indicate that clinical, morphologic, and some immunologic features of ALCL may mimic gastrointestinal carcinoma.

Adult↗

PubMed1992

Anti-CD34 immunoperoxidase staining in paraffin sections of acute leukemia: comparison with flow cytometric immunophenotyping.

Anti-CD34 is a monoclonal antibody that reacts with bone marrow progenitor cells and leukemic blasts, and is expressed on 30% to 50% of all acute leukemias. Detection of CD34 has previously been restricted to flow cytometric studies. To expand the utility of CD34, we immunostained 46 paraffin-embedded bone marrow specimens with acute leukemia; results were compared with flow cytometric studies. CD34 reactivity was also evaluated in nine chronic leukemia cases, 27 malignant lymphoma cases (Hodgkin's disease and non-Hodgkin's lymphoma), six normal bone marrow specimens, and three benign, hyperplastic lymph node specimens. All cases that were CD34 positive by flow cytometry (11 of 19 B-cell precursor acute lymphoblastic leukemia cases, one of six T-cell acute lymphoblastic leukemia cases, and seven of 21 acute myeloblastic leukemia cases) were also CD34 positive in paraffin sections. Both cell membrane and cytoplasmic staining was seen. The positivity percentage and fluorescence intensity by flow cytometry correlated with the estimated number of stained cells and the intensity of immunoperoxidase staining in 18 of 19 CD34-positive cases. The remaining bone marrow and lymph node cases studied were CD34 negative; prominent endothelial cell staining, however, was noted. This is the first report of anti-CD34 staining of acute leukemia in paraffin-embedded sections. In contrast to other monoclonal antibodies reactive in bone marrow paraffin sections with leukemia, anti-CD34 immunoperoxidase staining is limited to leukemic blasts and may provide useful diagnostic information when flow cytometric studies are not available.

Acute Disease↗

PubMed1992

Detection of Epstein-Barr virus genome in Ki-1 (CD30)-positive, large-cell anaplastic lymphomas using the polymerase chain reaction.

Ki-1 (CD30)-positive, large-cell anaplastic lymphoma (LCAL) is a distinctive subset of non-Hodgkin's lymphoma; morphologically, the neoplastic cells of LCAL may closely resemble Reed-Sternberg cell variants of Hodgkin's disease. The neoplastic cells in Hodgkin's disease are often CD30-positive, as are some of the transformed lymphocytes in infectious mononucleosis. Recent evidence suggests an etiologic role for the Epstein-Barr virus (EBV) in Hodgkin's disease. Because of the phenotypic similarities between Hodgkin's disease and LCAL, we used the polymerase chain reaction (PCR) to analyze eight specimens of LCAL for EBV genome. Diagnoses were established by paraffin section morphology and immunohistochemistry. For comparison, we also analyzed nine non-Hodgkin's lymphomas other than the LCAL type, three Hodgkin's disease specimens, and nine non-neoplastic lymph nodes. PCR was performed using DNA extracted from frozen tissue; DNA was amplified using two sets of oligonucleotide primers corresponding to the BamH1 W-fragment of the EBV genome. Amplified EBV genome was obtained from all specimens except for one mantle zone lymphoma, one diffuse mixed-cell lymphoma, and six non-neoplastic lymph nodes. EBV terminus region probing and in situ hybridization techniques, each less sensitive than PCR, were performed in selected cases in an attempt to corroborate our PCR results. Only 2 of 13 specimens contained EBV detectable by these other techniques, and neither specimen was a LCAL. In view of the high incidence of latent EBV infections in humans, the biologic significance of our PCR results is uncertain. Despite the detection of EBV genome by PCR in a high percentage of lymphomas, we were unable to substantiate an etiologic role for EBV in LCAL. The PCR technique may be too sensitive to provide meaningful data on the possible role of EBV in lymphomagenesis.

Antigens, CD↗

PubMed1992

CD30-positive, anaplastic large-cell lymphomas that express CD15 but lack CD45. A possible diagnostic pitfall.

We report the immunohistochemical and clinical features of two cases of morphologically typical anaplastic large-cell lymphoma. One patient had lymph node and focal visceral involvement, and the other patient had multiple-organ involvement by lymphoma. In both cases, the lymphoma cells were CD30 (Ber-H2) and CD15 (Leu-M1) positive and CD45 (common leukocyte antigen) negative--a phenotype that is commonly seen in Hodgkin's disease. This unusual phenotype in large-cell anaplastic lymphoma led to an initial misinterpretation in one of the cases. Large-cell anaplastic lymphomas are highly variable, both in immunophenotype and clinical presentation. Because of this variability, a broad immunophenotypic panel, in conjunction with morphological features, should be used to establish the correct diagnosis.

Adult↗

PubMed1991

Chronic active Epstein-Barr virus infection and virus-associated hemophagocytic syndrome.

We describe two unusual cases of Epstein-Barr virus infection that were complicated by the virus-associated hemophagocytic syndrome, predominantly involving the spleen. Both patients were young adult men who presented with fever, pancytopenia, and hepatosplenomegaly. Both had prompt symptomatic and hematologic improvement following splenectomy. Severe constitutional symptoms recurred in one patient 1 month after splenectomy, and he died of septicemia 2 months later. In both cases, there was prominent hemophagocytosis in the splenic red pulp. Some hemophagocytosis was also noted in the liver from the fatal case. Unexpectedly, no hemophagocytosis was detected in the bone marrow biopsy specimens or marrow aspirates obtained from these patients. The DNA hybridization studies detected Epstein-Barr virus genomes in spleen samples from both patients, and both patients had atypical patterns of serologic response to the virus, suggesting that a defective immune response may lead to an unrestrained viral proliferation. We conclude that there is an association between chronic active Epstein-Barr virus infection and the hemophagocytic syndrome, but that the tissue distribution of the hemophagocytosis may be variable.

Adult↗

PubMed1990

Down-regulation of phytochrome mRNA abundance by red light and benzyladenine in etiolated cucumber cotyledons.

Northern blot analysis revealed that a single 4.2 kb phytochrome mRNA species was detectable in cotyledons excised from five-day-old etiolated cucumber seedlings. Intact etiolated five-day-old cucumber seedlings were given a red light or benzyladenine treatment, and cotyledons were harvested at various times following treatment. The abundance of phytochrome mRNA in the cotyledons was quantitated using 32P-labeled RNA probes and slot blot analysis. By 2 h after irradiation the phytochrome mRNA level was reduced to 40% of the initial abundance and reaccumulation began by 3 h after irradiation. Reaccumulation of phytochrome mRNA to the time-zero dark control level was achieved by 10 h after treatment. A decrease in phytochrome mRNA abundance was evident by 2 h after benzyladenine treatment, and a maximal reduction to 45% of the time-zero dark control was attained by 4 h after treatment. No recovery of the phytochrome mRNA level was evident by 8 h after benzyladenine treatment. The abundance of actin mRNA was unaffected by benzyladenine treatment.

Actins↗

PubMed1990

Kappa light chain gene rearrangement in T-cell acute lymphoblastic leukemia.

Immunoglobulin and T-cell receptor gene rearrangement assays are sensitive methods of detecting clonality in lymphoproliferative disorders. The lack of lineage specificity of immunoglobulin heavy chain and T-cell receptor beta and gamma gene probes in acute leukemia is well established. However, immunoglobulin light chain gene rearrangement traditionally has been considered a highly specific indicator of a clonal B-lineage process. The authors describe a case of T-cell acute lymphoblastic leukemia in which Southern blot hybridization studies showed rearrangement of the T-cell receptor beta chain gene. Unexpectedly, the immunoglobulin kappa light chain gene also was rearranged; no immunoglobulin heavy chain gene rearrangement was seen. Kappa rearrangement was confirmed with the use of three restriction endonucleases. No rearrangements were seen from normal skin tissue, making a restriction enzyme site polymorphism highly unlikely. Northern blot studies showed a normal-size, T-cell receptor beta chain gene transcript; no immunoglobulin RNA was identified. These results describe the first reported case of kappa light chain gene rearrangement in a T-cell acute lymphoblastic leukemia. The findings emphasize the necessity of interpreting molecular hybridization studies in conjunction with routine morphology and immunophenotyping studies.

Aged↗

PubMed1990

Immunophenotypic aberrancy in adult acute lymphoblastic leukemia.

Some recent reports indicate a high frequency of immunophenotypic aberrancy in acute lymphoblastic leukemia (ALL). To investigate this issue with regard to adult ALL, the authors reviewed the immunophenotyping data from 39 cases analyzed in their clinical laboratory. Flow cytometric analysis of peripheral blood and/or bone marrow was performed with the use of a panel of 21 B-cell, T-cell, and myeloid monoclonal antibodies (MoAbs). The surface antigen profiles of the leukemic cells were compared with those of normal bone marrow and thymic counterparts, as defined by current models. Twenty-six cases were B-precursor ALL, 8 were T-ALL, and 3 were B-ALL (Burkitt's leukemia). Only two cases coexpressed lymphoid and myeloid antigens. In contrast, intralineage aberrancy was quite common. Immunophenotypes from 13 of 26 B-precursor ALL cases deviated from normal B-lineage marrow cells as defined by a recent classification. The T-ALL cases were also immunophenotypically heterogeneous. This high incidence of aberrant antigen expression in adult ALL suggests that leukemogenesis also involves aberrant differentiation rather than purely a process of maturational arrest.

Adolescent↗

PubMed1987

Comparison of tissue preparation methods for assay of nicotinamide coenzymes.

To prepare tissues for analysis of NAD(+), NADH, NADP(+), and NADPH, common practice is to freeze samples in liquid nitrogen, often followed by freeze-drying, before extraction in HCl or NaOH. With cucumber (Cucumis sativus L.) cotyledons, prefreezing in liquid nitrogen or slower freezing to -20 degrees C yielded substantially lower values for NADH and NADPH than obtained from samples homogenized immediately in acid or base. Freeze-drying after freezing in liquid nitrogen generally caused even lower values of those coenzymes. We suggest that direct extraction is more likely to yield accurate results with cotyledons and other plant parts.

Journal Article↗

PubMed1987

Kaposi's sarcoma appearing as a rectal ulcer.

This case report describes the occurrence of a painful rectal ulcer and associated fecal incontinence in a male homosexual with acquired immune deficiency syndrome. At biopsy, the ulcer proved to be Kaposi's sarcoma. The unusual location and the atypical gross appearance of this lesion underscore the need for an aggressive diagnostic approach to such ulcerative lesions. The advanced stage of the tumor at diagnosis and the patient's poor prognosis presented a difficult therapeutic dilemma, for which only palliative measures and local control were recommended.

Acquired Immunodeficiency Syndrome↗

PubMed1986

Effects of wounding on cytokinin activity in cucumber cotyledons.

Three known physiological responses to exogenous cytokinins were measured in wounded and nonwounded cotyledons from cucumber (Cucumis sativus L. cv Marketer) seedlings grown in darkness. Enhanced cell division, chlorophyll formation, and cotyledon expansion were detected in wounded cotyledons. The data suggest that wounding enhances endogenous cytokinin activity.

Journal Article↗

PubMed1982

Evaluation of h secretion relative to zeatin-induced growth of detached cucumber cotyledons.

Cytokinins promote expansion of cotyledons detached from seedlings of more than a dozen species. The zeatin-enhanced expansion of cucumber (Cucumis sativus L. cv Marketer) cotyledons was investigated. In addition, whether acid secretion is involved in wall loosening accompanying such accelerated growth was evaluated. For cotyledons abraded with carborundum or cut into either eight or 18 pieces, we detected no zeatin-enhanced acidification of the growth medium during growth periods of 3 days. Measurements of pH values on each surface of zeatin-treated, abraded cotyledons after 3 days of growth also showed no detectable acidification caused by the hormone. Furthermore, with several buffers at pH values ranging from 5 to 8, growth of nonabraded, abraded, or cut cotyledons with or without zeatin was independent of external pH. However, experiments restricted to about 12 hours indicated that certain acidic buffers enhanced growth of cotyledons cut into 18 pieces. Lastly, concentrations of fusicoccin that caused growth promotion equal to that of zeatin initiated substantial acidification of the medium. Collectively, these data suggest that zeatin-induced expansion of detached cucumber cotyledons is independent of H(+) secretion.

Journal Article↗

PubMed1982

Estimation of osmotic parameters accompanying zeatin-induced growth of detached cucumber cotyledons.

Water potential (psi), the osmotic potential (psi(pi)), and the pressure potential (psi(p)) of detached cotyledons isolated from Cucumis sativus L. cv Marketer seedlings after 0, 1.5, and 3 days growth with and without zeatin were determined. From zero time to 3 days, cotyledons incubated without exogenous zeatin exhibited a slight decrease in psi (from -0.4 to -1.0 bars), while those grown with zeatin developed even more negative values (about -4 bars). Both groups showed rising psi(pi) values (decreases in solutes per unit volume), but this rise was more dramatic in those treated with zeatin. These data indicate that the capacity of zeatin-treated cotyledons to take up water more rapidly than controls and thus expand faster must be due to wall loosening, as reflected in psi(p) values which declined during 3 days from about +11 bars to about +1.4 bars.It was also found that freshly detached cotyledons or those grown without exogenous zeatin exhibited osmoregulation in polyethylene glycol (PEG) solutions. That is, while cotyledons initially lost H(2)O into certain PEG solutions, their psi values decreased over time and they began absorbing water after 1 to 4 hours. After 3 days growth, zeatin-treated cotyledons had lost most of this capacity of osmoregulate. It seems likely that osmoregulation in cotyledons not treated with zeatin is due to wall loosening rather than changes in psi(pi). Zeatin-treated cotyledons with already loosened walls may not have this option to deal with water stress and thus simply come to equilibrium with external PEG solutions.

Journal Article↗

PubMed1981

Cytokinin-induced wall extensibility in excised cotyledons of radish and cucumber.

The mechanism of cytokinin-induced cell expansion in cotyledons excised from dark-grown seedlings of radish (Raphanus sativus L.) and cucumber (Cucumus sativus L.) was studied. Cotyledons were incubated in dim light with or without 17 micromolar zeatin for periods up to 3 days. Fresh weights and osmotic potentials were measured daily. Cell wall extensibility properties were measured before and after the growth period. Also, experiments in which radish cotyledons were grown in mannitol solutions of various concentrations were performed. Comparisons of growth rates and increases of tissue osmotic potentials (toward zero) during growth without mannitol indicate that wall extensibility increased during the growth period and that this extensibility was enhanced by zeatin.Extensibility values derived from growth rates in mannitol provided indirect evidence of zeatin-increased wall extensibility. These conclusions were verified by direct measurements of plasticity with an Instron extensiometer. Thus, growth stimulation of excised cotyledons by cytokinins apparently involves wall loosening, in addition to previously demonstrated increases of K(+) absorption and formation of reducing sugars.

Journal Article↗

PubMed1978

Properties of pea seedling uracil phosphoribosyltransferase and its distribution in other plants.

A uracil phosphoribosyltransferase (UMP-pyrophosphorylase) was found in several angiosperms and was partially purified from epicotyls of pea (Pisum sativum L. cv. Alaska) seedlings. Its pH optimum was about 8.5; its required approximately 0.3 mm MgCl(2) for maximum activity but was inhibited by MnCl(2); its molecular weight determined by chromatography on Sephadex G-150 columns was approximately 100,000; its K(m) values for uracil and 5-phosphorylribose 1-pyrophosphate were 0.7 mum and 11 mum; and it was partially resolved from a similar phosphoribosyltransferase converting orotic acid to orotodine 5'-phosphate. Enzyme fractions containing both uracil phosphoribosyl transferase and orotate phosphoribosyltransferase converted 6-azauracil and 5-fluorouracil to products with chromatographic properties of 6-azauradine 5'-phosphate and 5-fluorouridine 5'-phosphate. Uracil phosphoribosyltransferase probably functions in salvage of uracil for synthesis of pyrimidine nucleotides.

Journal Article↗