Mechanisms of resistance to nucleoside analogue chemotherapy in mantle cell lymphoma: a molecular case study.
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Antimetabolites, Antineoplastic↗
Biomedical subjects
R Coupland
Publications and source records attributed to R Coupland.
Recurrent Epstein-Barr virus associated disease in a cardiac transplant patient: evolution from plasmacytic hyperplasia to diffuse large cell lymphoma.
An Epstein-Barr virus (EBV)-seronegative 31-year-old male underwent cardiac transplantation in 1991 for congenital cardiomyopathy. He presented with a protracted course of waxing and waning lymphadenopathy beginning four years after transplantation with eventual progression to a fulminant EBV-positive large cell lymphoma eight years after transplantation. Risk factors for the development of post-transplant lymphoproliferative disease in this patient, the importance of a standardized approach to pathology in assessing therapeutic options, and the management strategies used are discussed.
Adult↗
Angiotropic lymphoma: an immunophenotypically and clinically heterogeneous lymphoma.
Angiotropic lymphoma (AL) is an uncommon lymphoma often presenting with nonspecific clinical features and having a high mortality rate. Although not specifically recognized by the Revised European-American Classification of Lymphoid Neoplasms, it likely will appear as a subtype of diffuse large B-cell lymphoma in the upcoming WHO classification. Some authors may also consider it to be a subtype of cutaneous lymphomas. Recent studies have reported an immunophenotypic heterogeneity of AL, and in rare instances, an association with other NHL. To further characterize AL, we studied the immunophenotype by immunohistochemistry for CD5, CD10, CD20, bcl-2, and bcl-6 in 18 cases of B-cell AL identified at three medical centers in North America. Bcl-2 gene rearrangement status by polymerase chain reaction and Epstein Barr virus status by in situ hybridization also were evaluated. Eight men and 10 women were identified with AL (median age 71 years). Eleven patients were diagnosed in life and seven were diagnosed at autopsy. Neurologic symptoms were the most common presentation, seen in six patients. Skin was the most commonly biopsied site. All showed classic intravascular localization; in two cases, there was also a minor diffuse large cell lymphoma component observed in some organs. Most (89%) of the cases expressed bcl-2 protein; CD10, bcl-6 and CD5 were each expressed in 22% of cases. Based on CD5 and CD10 expression, three major groups were evident: CD5-, CD10- (11 cases); CD5+, CD10- (3 cases), and CD5-, CD10+ (3 cases). Even though a follicle center lymphoma preceded the AL in one patient, we did not detect bcl-2 gene rearrangement in any of these cases. All cases were negative for Epstein Barr virus. Of the five treated with chemotherapy, two achieved a complete remission. Based on these findings, we conclude that ALs are clinically and immunophenotypically heterogeneous and may represent more than one pathogenetic entity. In some instances AL may be preceded by another lymphoproliferative disorder, raising the possibility that some cases of AL may represent a transformation from another type of lymphoma. Cutaneous manifestations of AL are common; however, it appears to be a systemic lymphoma. Although often fatal, patients with AL who are diagnosed early and treated with chemotherapy may achieve remission.
Aged↗
Seroprevalence of Neospora caninum in beef cattle in northern Alberta.
Blood samples were collected from 1806 pregnancy-tested cows from 174 herds at a northern Alberta auction mart in the fall of 1998. One hundred sixty-two (9.0%) of these samples were positive for antibodies to N. caninum. Thirty-five of 260 samples (13.5%) collected from the same region in the 1980s were also serologically positive for N. caninum.
Alberta↗
Effect of radiation on cytokine and cytokine receptor messenger-RNA profiles in p53 wild and mutated human glioblastoma cell lines.
OBJECTIVE: Glioblastoma cells produce cytokines with proinflammatory or immunosuppressive properties, or both, which, in addition to altered p53 gene expression, have been shown to be associated with glioblastoma resistance to radiotherapy. The reported data concerning cytokines have been isolated and sometimes discordant, and a comprehensive profile analysis of cytokines and their corresponding receptors in irradiated glioblastomas has received limited attention. The object of this study was to test the hypothesis that radiation alone in clinically relevant doses would not significantly alter expression of endogenous cytokines and their receptors in human glioblastoma celll ines with wild-type and mutant p53. DESIGN AND METHOD: Culture specimens of 4 glioblastoma cell lines of different p53 gene expression (U87, U118, U251, U373) were irradiated with cobalt 60 at a dose of 10 Gy. After 48 hours, radiosensitivity was defined through a colony formation assay, cell cycle distribution was analyzed by flow cytometry, and cytokine and cytokine receptor messenger-RNA (mRNA) profiles were defined with an RNase protection assay. Different single doses of radiation at varying time intervals after culture were applied also to wild-type p53 cell lines. RESULTS: All cell lines were relatively radioresistant at lower doses of 1 and 2 Gy. Immunosuppressive cytokine and cytokine receptor mRNA of the Th2 (IL-13Ralpha, IL-4) and Th3 family (TGF-beta1, 2 and 3, TGF-betaRI and RII) were expressed. In contrast, only 2 proinflammatory Th1 cytokine receptor genes (IFN-gammaRa and IFN-gammaRbeta), but no significant Th1 cytokine gene expression, were detected. Even though the population examined included a large fraction of reproductively dead cells, cytokine and cytokine receptor mRNA profiles were not altered significantly by irradiation in all cell lines, regardless of the p53 status. CONCLUSION: These results suggest that cobalt irradiation alone at clinically relevant doses does not significantly alter the cytokine and cytokine receptor profiles in human glioblastoma cell lines.
Cobalt Radioisotopes↗
Clinical and legal significance of fragmentation of bullets in relation to size of wounds: retrospective analysis.
OBJECTIVE: To examine the relation between fragmentation of bullets and size of wounds clinically and in the context of the Hague Declaration of 1899. DESIGN: Retrospective analysis of prospectively collected data on hospital admissions. SETTING: Hospitals of the International Committee of the Red Cross. SUBJECTS: 5215 people wounded by bullets in armed conflicts (5933 wounds). MAIN OUTCOME MEASURES: Grade of wound computed from the Red Cross wound classification and presence of bullet fragments on radiography. RESULTS: Of the 347 wounds with fragmentation of bullets, 251 (72%) were large wounds (grade 2 or 3)-that is, those with a clinically detectable cavity. Of the 5586 wounds without fragmentation of bullets, 2915 (52.1%) were large wounds. Only 7.9% (251/3166) of large wounds were associated with fragmentation of bullets. CONCLUSIONS: Fragmentation of bullets is associated with large wounds, but most large wounds do not contain bullet fragments. In addition, bullet fragments may occur in wounds that are not defined as large. Fragmentation of bullets is neither a necessary nor sufficient cause of large wounds, and surgeons should not diagnose extensive tissue damage because of the presence of fragments on radiography. Such findings also do not necessarily represent the use of bullets which contravene the law of war. Future legislation should take into account not only the construction of bullets but also their potential to transfer energy to the human body.
Humans↗
Primary pericardial synovial sarcoma: a case report and literature review.
Primary synovial sarcoma of the heart is a rare tumor, with only six previous cases having been reported in the literature. Treatment has included surgery with or without chemotherapy. We present the first case of a documented synovial sarcoma arising from the pericardium in a 19-year-old man. Molecular analysis for t(X; 18) SYT-SSX gene fusion was positive. Radiation treatment was given postoperatively to the entire heart with a boost to the area where the margins were positive.
Adult↗
Immunohistochemical detection of E2F-1 in non-Hodgkin's lymphomas: a survey of 124 cases.
E2F-1 is a transcription factor that mediates cell cycle progression from the G1 to S phase and is normally regulated by a group of proteins, including cyclin D1. Although deregulation of E2F-1 is implicated in neoplastic transformation, in situ examination of this protein has not been performed to date. Using an immunohistochemical technique applied to routinely fixed, paraffin-embedded tissue sections, we evaluated E2F-1 expression in reactive lymphoid tissues and in 124 cases of non-Hodgkin's lymphoma (NHL) of various types. In reactive lymphoid tissues, E2F-1 was expressed predominantly by large noncleaved cells in germinal centers and by a small subset of cortical thymocytes. Mantle zones and splenic marginal zones were negative. Among the NHLs, four types had a relatively high percentage (> 20%) of E2F-1-positive cells: mantle cell lymphoma (19 of 19), lymphoblastic lymphoma (5 of 5), small noncleaved cell lymphoma (4 of 6), and hepatosplenic gammadelta T-cell lymphoma (3 of 3). The consistent detection of many E2F-1-positive cells in mantle cell lymphoma is in contrast to other small B-cell NHLs (n = 29), which had relatively few (< 10%) E2F-1-positive cells. This finding suggests that immunohistochemical staining for E2F-1 as a supplement to the existing markers, such as cyclin D1, might be useful in the differential diagnosis of NHLs composed of small B cells.
Carrier Proteins↗
Arrest of spermatogenesis and defective breast development in mice lacking A-myb.
The Myb gene family currently consists of three members, named A-, B- and c-myb. These genes encode nuclear proteins that bind DNA in a sequence-specific manner and function as regulators of transcription. In adult male mice, A-myb is expressed predominantly in male germ cells. In female mice, A-myb is expressed in breast ductal epithelium, mainly during pregnancy-induced ductal branching and alveolar development. We report here that mice homozygous for a germline mutation in A-myb develop to term but show defects in growth after birth and male infertility due to a block in spermatogenesis. Morphological examination of the testes of A-myb-/- males revealed that the germ cells enter meiotic prophase and arrest at pachytene. In adult homozygous null A-myb female mice, the breast epithelial compartment showed underdevelopment of breast tissue following pregnancy and the female mice were unable to nurse their newborn pups. These results demonstrate that A-myb plays a critical role in spermatogenesis and mammary gland development.
Animals↗
Plasmacytoma of the oral cavity and jaws: a clinicopathologic study of 13 cases.
Plasmacytoma of the jaw bones and oral cavity, as in other anatomic sites, comprises three distinct entities: multiple myeloma, solitary plasmacytoma of bone, and extramedullary plasmacytoma. This article is a retrospective study of 13 cases; 9 occurred in the mandible and 4 in the maxilla. The most common radiographic finding was a radiolucency that many times was superimposed on the roots or apices of nearby teeth. The most common symptom was localized pain, and the most frequent clinical sign was a raised red lesion on the alveolar ridge. The disease affects older persons, and the posterior mandible is the most frequently reported location. The degree of dysplasia of tumor cells was evaluated as there is a reported correlation with survival rates.
Adult↗
Abdominal wounds in war.
The reported mortality rate associated with abdominal wounds sustained in war varies considerably because of the heterogeneity of wounds and the different circumstances under which figures have been collected rather than different treatment strategies. This review draws together a personal experience, reports from ten wars, and information from a database for war wounded into an analysis of abdominal wounds. The analysis attempts to bring understanding to why people die with abdominal wounds in war and so clarifies logistic and treatment issues.
Abdominal Injuries↗
Pump up your PT IQ.
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Centers for Medicare and Medicaid Services, U.S.↗
The management of fractures from missiles.
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Bone Nails↗
Outcome of arterial repairs in 23 consecutive patients at the ICRC-Peshawar hospital for war wounded.
Arterial injuries represent a formidable challenge to surgeons working in war zone conditions. A series of 23 consecutive patients with combat wounds from the Afghan conflict with acute arterial injury were treated at the ICRC hospital in Peshawar. The mean injury-treatment delay (lag time) was 34 hours, with 14 of the 23 patients (60%) treated more than 12 hours after injury. The overall amputation rate was 65%, but only 22% for patients revascularized within 12 hours of injury and 93% for those undergoing surgery after 12 hours. This was a highly significant statistical difference (Chi-square > 13.0, p < 0.005). We recommend attempting revascularization procedures only in patients seen within 12 hours of sustaining a military-type injury to an artery in an extremity.
Acute Disease↗
t(11;18)(q21;q21.1): a recurring translocation in lymphomas of mucosa-associated lymphoid tissue (MALT)?
A distinct subtype of extranodal malignant lymphoma derived from mucosa-associated lymphoid tissues (MALT) has recently been defined. We have detected an acquired t(11;18)(q21;q21.1) in a patient with a MALT lymphoma of the stomach. This translocation has previously been described in two other patients with extranodal lymphoma. The BCL2 oncogene, which is located at band 18q21.3 and is activated by the t(14;18)(q32;q21) in follicular lymphoma, was not rearranged in this case. This newly identified t(11;18) may be a recurring translocation specifically associated with MALT lymphomas. Genes located at the breakpoint sites of chromosome 11 and/or chromosome 18 may be crucial to the pathogenesis of this type of malignant lymphoma.
Base Sequence↗
Community liaison. Life's rich pattern.
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Aged↗
Stable T3- and T3+ subclones derived from the mosaic human T cell leukemia cell line, CEM.
An unexplained feature of the human T lymphoblastic leukemia cell line, CEM, is a heterogeneous expression of surface membrane T3-TCR complex. CEM cells constitutively maintain two distinct populations whereby a minority of cells (5 to 16%) express T3 but the remainder do not. From the parental cell line, we have derived stable subclones in which all cells express surface T3 and companion subclones that lack surface T3. Inasmuch as surface T3 expression is contingent on assembly and coexpression of the multichain T3 protein complex with the TCR, we compared the surface T3+ and T3- subclones for their rearrangement and expression of genes of the T3-TCR complex. Restricted DNA of both subclone types showed the identical monoclonal pattern of TCR gene rearrangement seen in the mosaic parental CEM line. Northern blot analysis revealed mRNA transcripts of TCR beta subunit and T3 delta in both the surface T3+ and T3- subclones. However, surface T3+ subclones transcribed abundant full length (1.5-kb) TCR alpha mRNA in contrast to the surface T3- subclones in which TCR alpha transcripts were undetectable. Lack of TCR alpha gene transcription was not attributable to either unrearranged or aberrantly rearranged TCR alpha genes because exposure of surface T3- cells to phorbol ester induced a rapid (15-min) and progressive accumulation of full length (1.5-kb) TCR alpha mRNA. This was followed by surface membrane T3 expression in 24 to 72 h. We conclude that the unusual phenotypic mosaicism of CEM cells is attributable to a reversible lack of transcription of the TCR alpha gene.
Antigens, Differentiation, T-Lymphocyte↗