CMV-induced hemorrhagic cystitis as a complication of peripheral blood stem cell transplantation: case report.
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Benzamides↗
Biomedical subjects
M Ozdemirli
Publications and source records attributed to M Ozdemirli.
Differentiating lymphoblastic lymphoma and Ewing's sarcoma: lymphocyte markers and gene rearrangement.
We encountered a child with an intraosseous small round cell tumor that was negative for LCA, CD20 (L26), and CD3 and positive for vimentin, CD99 (MIC-2), and periodic acid-Schiff. The tumor exhibited rosette-like formations. This case was initially interpreted as Ewing's sarcoma (ES); however, additional studies revealed positivity for CD79a, CD43, and TdT expression, and an immunoglobulin heavy chain gene rearrangement (IgH-R) by polymerase chain reaction (PCR) established this to be a precursor B-lymphoblastic lymphoma. Because the differential diagnosis of ES and lymphoblastic lymphoma can be difficult and the differential diagnostic value of leukocyte antigens and immunoglobulin heavy chain gene rearrangement studies have not been fully evaluated, we conducted a more extensive investigation on 33 (21 soft tissue and 12 intraosseous) ES cases. Cases were retrieved from the files of the Department of Pathology at Georgetown University and from the Soft Tissue Registry of the Armed Forces Institute of Pathology. The cases were studied by light microscopy, immunohistochemistry, and PCR for IgH-R and T cell receptor gamma chain gene rearrangement (Tgamma-R). There were 17 females and 16 males; the mean age was 29.3 years. Locations included the extremities (n = 17) and trunk (n = 16). All cases fit the ES spectrum by light microscopy and immunohistochemistry, as previously determined, and were negative for lymphoid markers (LCA, CD3, CD20, CD43, CD79a, and TdT), CD10 and CD34. CD99 was positive in 31/33 and bcl-2 was weakly positive in 13/33 cases. All 21 cases studied for gene rearrangements by PCR were negative for IgH-R and Tgamma-R. Distinction of intraosseous lymphoblastic lymphoma from ES may be difficult because lymphomas may occasionally exhibit unexpected morphologic and immunophenotypic properties including LCA, CD3 and CD20 negativity and cytokeratin positivity. Additional analysis using CD79a, CD43, TdT, and PCR should be performed to avoid misdiagnosis. True ES is negative for lymphoid markers including CD79a, CD43, and TdT, as well as for IgH-R and Tgamma-R.
12E7 Antigen↗
Scleredema of Buschke associated with Waldenström's macroglobulinaemia.
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Aged↗
Diagnosis at first glance: hairy black colonies in resected prosthetic aortic valve.
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Antibodies, Bacterial↗
Molecular and cellular mechanisms regulating T and B cell apoptosis through Fas/FasL interaction.
Fas (CD95) and Fas ligand (FasL) are a receptor/ligand pair critically involved in lymphocyte homeostasis and peripheral tolerance such that genetic defect in either Fas or FasL results in an autoimmune lymphoproliferative syndrome. Fas is a type I transmembrane protein and a member of the tumor necrosis factor receptor (TNFR) family whereas FasL is a type II transmembrane protein and a member of TNF family. Binding of Fas by FasL induces apoptosis of the Fas-expressing cells. In the past few years, Fas/FasL interaction has been connected to a series of important phenomena previously viewed as independent immune processes. The activation-induced T cell death (AICD) and the FasL-mediated cytotoxicity by activated T cells are two critical mechanisms that can account for most of these phenomena. It is in the context of the two mechanisms that we discuss in this review the molecular and cellular events that occur during T/T and T/B interactions that account for the down-regulation of the immune response. We have also discussed recent advances in the areas of FasL gene regulation, lymphokine regulation of AICD, and regulation of B cell susceptibility to FasL. Investigation in these areas should help elucidate the role of Fas/FasL in the complex network of regulatory mechanisms that control immune response and autoimmunity.
Animals↗
Human papillomavirus 18 oncoproteins E6 and E7 enhance irradiation- and chemotherapeutic agent-induced apoptosis in p53 and Rb mutated cervical cancer cell lines.
Tumor suppressor genes p53 and Rb are important in cell cycle control. Necessity of wild type p53 is implicated in irradiation-induced apoptosis. Numerous tumor cells carry p53 mutations and yet are sensitive to irradiation or chemotherapeutic agents. Therefore p53-and Rb-independent pathways must exist to account for irradiation-induced apoptosis. We evaluated the apoptotic response of a p53- and Rb-mutated, Human Papilloma Virus (HPV) negative cervical cancer cell line (C33a), and C33a cell lines infected with HPV 18 oncoproteins E6, E7, and E6&7 using recombinant retrovirus to various apoptosis-inducing agents including gamma irradiation, mitomycin C (MMC), and staurosporine (SSP). Apoptosis was measured by avidinebiotin tunnel staining method. Our results showed significant apoptosis in C33a cell lines in response to gamma-irradiation, MMC, and SSP. Moreover, apoptosis was enhanced when HPV 18 E6, and E6&7 infected C33a cell lines were treated with irradiation, MMC, and SSP. HPV 18 E7 infected C33a cell lines enhanced the apoptotic response to irradiation and to MMC, but not to SSP. In conclusion, our results imply the presence of a p53- and Rb-independent pathway in irradiation-induced apoptosis in cervical cancer cell lines: this effect is even more evident in HPV oncoprotein infected cell lines. The radiosensitizing effects of HPV oncoproteins may lead to new perspectives in the treatment of cervical cancer.
Apoptosis↗
Precursor B-Lymphoblastic lymphoma presenting as a solitary bone tumor and mimicking Ewing's sarcoma: a report of four cases and review of the literature.
Precursor B-lymphoblastic lymphoma (B-LBL) may present as a solitary bone tumor. Fewer than 10 cases with a proven precursor B-cell phenotype have been reported in the English literature. In this report, we describe four cases of B-lymphoblastic lymphoma presenting as a localized intraosseous mass, which clinically and histologically mimicked Ewing's sarcoma. Three tumors occurred in the tibia and one in the humerus. In all four cases, the initial diagnosis was either "Ewing's sarcoma" or "consistent with Ewing's sarcoma." All four patients were female. Three were children and one was an adult; mean age was 12.5 years (range, 4 to 31 years). All had extremity pain without significant constitutional symptoms. In three cases, the tumors were osteolytic on radiographic evaluation, and in one case, osteosclerotic. Immunohistochemical stains on paraffin-embedded tissue showed that the neoplastic cells expressed terminal deoxynucleotidyl transferase, CD43, vimentin, and CD99 (MIC2 gene product) in all cases. Three cases were negative for CD45. CD79a was positive in all four cases studied; however, CD20 (L26) was positive in only two of four cases. CD3 was negative in all cases. Two cases showed focal granular cytoplasmic staining for keratin. Two cases analyzed by polymerase chain reaction (PCR) revealed clonal rearrangement of the immunoglobulin heavy chain (IgH) gene. Follow-up revealed that the three pediatric patients, who received a high-dose multiagent chemotherapy regime for LBL, are disease free at follow-up intervals of more than 1, 11, and 12 years, respectively. The adult patient died two years after diagnosis with disseminated disease. Although rare, B-lymphoblastic lymphoma should be considered in the differential diagnosis of small round cell tumors of bone. A diagnosis of Ewing's sarcoma should be made only after complete immunophenotyping and, if necessary, molecular diagnostic tests to exclude lymphoblastic lymphoma. A limited panel of antibodies can lead to an erroneous diagnosis; B-lymphoblastic lymphoma may be negative for CD45 and CD20 but positive for CD99 and even for keratin, mimicking Ewing's sarcoma. Correct diagnosis is extremely important because LBL usually is curable in the pediatric age group with appropriate therapy.
Adult↗
Hodgkin's disease presenting as a solitary bone tumor. A report of four cases and review of the literature.
BACKGROUND: Hodgkin's disease (HD) rarely presents as a solitary bone tumor. Fewer than 20 such cases have been reported in the English literature; many of these were reported prior to the development of immunohistologic markers for HD and T- and B-cell lymphomas. In this report, we describe four cases of HD that presented as a localized solitary mass in bone; the diagnosis was confirmed by immunohistochemical studies in all cases. METHODS: The biopsy specimens of four cases identified in our files were studied by conventional histopathology and immunohistochemistry. Clinical data and follow-up information were obtained for all patients. RESULTS: Three cases presented as a localized, solitary mass in the ilium and one case in the vertebra (T12). Three patients were female and one male. The average age was 43 years. Three of the patients presented with lower back pain without constitutional symptoms. All had solitary osteoblastic lesions. All four cases were diagnostic problems, and the diagnosis was confirmed in each case only after finding lymph node involvement. Bone biopsies showed fibrosis and a mixed inflammatory infiltrate with rare atypical cells. All four patients were subsequently found to have nodal involvement by HD. The histology of the associated nodal disease was mixed cellularity in two cases and nodular sclerosis in two. On immunohistochemical staining, the neoplastic cells in all cases expressed CD15 and CD30 and lacked CD45 and other B- and T-cell antigens. Three patients who were treated for HD are alive and well, 1, 6, and 14 years later. CONCLUSIONS: Although rare, HD should be considered in the differential diagnosis of solitary bone lesions. Most patients who present with apparently solitary HD of bone prove to have nodal involvement. Long-term survival is possible with aggressive treatment.
Adult↗
Fas (CD95)/Fas ligand interactions regulate antigen-specific, major histocompatibility complex-restricted T/B cell proliferative responses.
The effect of Fas ligand (FasL) cytotoxicity on T/B collaboration was examined in vitro using cloned T helper 1 cells and antigen-pulsed, activated B cells. We compared antigen-pulsed B cells that had been activated through different membrane receptors (IgM, CD14 and CD40) for their ability to induce T cell proliferation and to respond to T cell help. We also used a Fas-Ig fusion protein, an inhibitor of FasL-mediated cytotoxicity, to determine the effect of FasL cytotoxicity on the T and B cell proliferative responses. The data show that the extent of both T and B cell proliferative responses correlate with the relative resistance of activated B cell populations to FasL cytotoxicity. Moreover, both T and B cell proliferation could be enhanced by Fas-Ig. Our results demonstrate that FasL cytotoxicity is a negative regulatory mechanism for both T and B cell proliferative responses and that Fas-Ig can be an immunopotentiating agent for both T and B cell immunity.
Animals↗
The cytotoxic process of CD4 Th1 clones.
Previous studies have demonstrated that murine CD4 Th1 cells lack perforin and use a pathway distinctive from CD8 CTL to express cytotoxicity. Whether the cytotoxic process of Th1 cells can be separated into identifiable stages and how these differences affect this process were determined in this study. We have resolved the cytotoxic process of Th1 clones into three stages identical with those of CD8 CTL, namely, conjugate formation/activation, lethal hit, and effector-independent programming for target DNA fragmentation. By comparing the cytotoxic processes between Th1 clones on Ag-pulsed targets and (PMA+A23187)-activated Th1 clones on unpulsed targets, we have also demonstrated that 1) the requirement of CD4 Th1 cells for de novo synthesis of cytotoxic machinery was partly responsible for the lag time in the induction of target DNA fragmentation by Th1 clones; 2) lethal hit was delivered rapidly; 3) lethal hit under forced contact by centrifugation did not need extracellular Ca2+ and Mg2+; 4) without centrifugation, lethal hit required extracellular Mg2+, but not Ca2+; 5) the average functional half life of the cytotoxic machinery was 54 +/- 24 (n = 4) min. The data demonstrate that the cytotoxic process of Th1 clones uses an activation-dependent cytotoxic machinery to deliver a short-lived, short-ranged, and quick-acting lethal hit to target, which induces a program in target for DNA fragmentation.
Animals↗
A novel cytotoxicity of CD4+ Th1 clones on heat-shocked tumor targets. I. Implications for internal disintegration model for target death and hyperthermia treatment of cancers.
A novel cytotoxicity, which is normally hidden but unveiled upon interacting with heat-shocked tumor target, has been identified in CD4+ Th1 cells. When TNF-resistant, Ag-presenting tumor targets were heat shocked, the cytotoxicity by specific Th1 clones was significantly enhanced. Interestingly, the DNA of heat-shocked, unpulsed targets including Ia- tumor cells were also fragmented by Th1 clones. In contrast to the Ag-dependent, MHC-restricted cytotoxicity, the heat-shock-induced sensitivity to Th1 clones was a) Ag independent and MHC unrestricted, b) insensitive to CD4-mAb, c) resistant to actinomycin D and cycloheximide, and d) greatly enhanced by cholera toxin, PGE1, PGE2, and dibutyryl cAMP. This novel cytotoxicity was inhibited by mAb specific to lymphocyte function-associated Ag-1 and intercellular adhesion molecule-1. Upon culturing at 37 degrees C, mildly heat-shocked target cells gradually recovered, indicating that the heat-shock-induced sensitivity was transient and reversible. The implication of this study for a signal-induced internal disintegration mechanism for target death is discussed. The novel cytotoxicity of CD4+ Th1 cells may be an important mechanism of immune regulation under febrile conditions and an underlying mechanism for the hyperthermia treatment of cancers.
Animals↗
Stage-specific increases in cathepsin B messenger RNA content in human colorectal carcinoma.
Cathepsin B mRNA levels and banding patterns were characterized in human colorectal mucosa and carcinoma tissues from patients with tumors of different Dukes' stages. Quantitation of mRNA content using slot blot hybridization demonstrated an increase in cathepsin B message in seven of eight tumor tissues with an average increase of 3.5-fold over patient-matched control mucosa samples. This tumor-specific increase in cathepsin B mRNA confirms and extends our previous observation that cathepsin B enzyme specific activity levels are significantly elevated in colorectal carcinomas. In fact, the increase in mRNA levels is greater and more consistent than the observed increase in enzyme activity, suggesting that posttranscriptional or posttranslational regulation of cathepsin B expression occurs in colorectal tumors. The mRNA data also support our earlier observation that cathepsin B enzyme activity levels are inversely correlated with Dukes' stage. The tumor-specific increase in cathepsin B mRNA content is almost 4 times greater in earlier stage (Dukes' A and B) tumors than in later stage (Dukes' C and D) tumors. Thus, increased cathepsin B gene expression is particularly characteristic of tumors which are in the process of invading the bowel wall or local tissues compared with tumors which have already spread to more distant sites. Northern blot data on cancer/normal pairs indicate that the increase in cathepsin B mRNA in colorectal carcinoma is due primarily to changes in the amount of the 2.2- and 4.0-kilobase transcripts which are seen in control tissue. However, low levels of two additional cathepsin B mRNA transcripts (1.5 and 3 kilobases in size) were also observed in tumor tissue.
Biomarkers, Tumor↗
On the nature of cellular ADP-ribosyltransferase from rat liver specific for elongation factor 2.
A cellular ADP-ribosyltransferase, specific for elongation factor 2 (EF-2), is found in extracts from rat liver. Co-migrating with EF-2 throughout purification, this activity is, moreover, located in the protein bands corresponding to EF-2 after native or sodium dodecyl sulfate polyacrylamide gel electrophoresis. The observed activity is thus implicated to be an inherent property of EF-2. Preincubation of EF-2 with GuoPPCH2Pox inhibits endogenous, but not diphtheria toxin catalyzed ADP-ribosylation.
ADP Ribose Transferases↗