Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019829 (Hodgkin's disease)
 30,247 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Individuals infected with HIV (Human Immunodeficiency Virus) frequently develop B cell non-Hodgkins lymphoma. Although previous studies have failed to document the presence of HIV sequences in these tumors, the recent demonstration of malignant transformation of primary B lymphocytes by HIV-1 has prompted us to reinvestigate this issue. We have examined DNA extracted from 7 lymphomas and 5 lymphadenopathy specimens for HIV LTR (long terminal repeat), gag, and tat sequences using the polymerase chain reaction (PCR). All samples produced products of the expected size with primers for these regions, indicating the presence of HIV proviral sequences in these tissues. The amount of provirus in the tissue was estimated by normalizing the amount of HIV product to the amount of product for the cellular myc gene or beta globin gene. Products were quantitated during the exponential phase of DNA accumulation. These studies indicated that provirus was present at approximately one copy per cell in the 7 lymphoma samples and in 4 of the 5 lymphadenopathy samples. These results are consistent with a direct role for virus in the initiation of lymphoma. Studies to determine whether provirus resides in the lymphoma cells per se will be necessary to further substantiate this hypothesis.
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PMID:Does HIV infection of B lymphocytes initiate AIDS lymphoma? Detection by PCR of viral sequences in lymphoma tissue. 149 Mar 78

The use of clonospecific probes has recently been employed for the detection of minimal residual disease in B- and T-cell acute lymphoblastic leukemias. However, these methods are predicated upon the successful amplification of the V-D-J rearrangement in the genome of the tumor cells by the polymerase chain reaction (PCR). In order to determine whether the type of B-cell lymphoid malignancy influenced the rate of success of amplifying the region of the immunoglobulin heavy chain gene rearrangement in these lesions, we studied 41 morphologically and immunologically well characterized B-cell neoplasms. DNA was extracted from frozen tissue of the lymphomas and leukemias, and subjected to PCR amplification using a 5' immunoglobulin heavy chain gene variable region consensus Framework 3 region (FR3) primer, and a 3' consensus primer for the immunoglobulin heavy chain joining region. One or two distinct bands, representing the rearranged immunoglobulin heavy chain gene, were detected in six of six small non-cleaved cell lymphomas, five of five small lymphocytic lymphomas, four of six acute lymphoblastic leukemias, four of six follicular lymphomas, three of six diffuse mixed small and large cell lymphomas, one of six diffuse large cell lymphomas, and one of six immunoblastic large cell lymphomas; all control cases of lymphocyte predominant Hodgkin's disease (5/5) and reactive follicular hyperplasia (5/5) were negative. We therefore conclude that the type of B-cell neoplasm influences the ability to detect immunoglobulin gene rearrangements by PCR with currently used consensus primers.
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PMID:Variable rate of detection of immunoglobulin heavy chain V-D-J rearrangement by PCR: a systematic study of 41 B-cell non-Hodgkin's lymphomas and leukemias. 149 28

Silver-intensification methods described in the literature for the diaminobenzidine (DAB) and diaminobenzidine-nickel (DAB/Ni) endproduct of the peroxidase reaction were compared in model systems after immunoperoxidase and in situ hybridization. First, these methods were compared in immunohistochemical model systems, using the demonstration of glial fibrillar acidic protein (GFAP) and prostate-specific antigen (PSA) in paraffin sections of human brain and prostate tissue, respectively. When DAB without Ni was used as substrate, tissue argyrophilia caused considerable background staining. Only when this tissue reactivity was quenched with, e.g., CuSO4 with H2O2 or thioglycolic acid, were the results acceptable. A considerable improvement in the signal-to-noise ratio could be obtained when nickel was included in the substrate mixture. The methods that proved to be best for demonstration of GFAP and PSA made use of acid developer solutions. Subsequently, these methods were compared with other sensitive immunostaining methods for demonstration of the gamma-delta T-cell receptor in frozen lymphoid tissue. In this model a considerable increase in the number of positive cells could be obtained using silver intensification. The different methods using DAB/Ni were also compared for use in DNA in situ hybridization (DISH). In this case two model systems were used: human papilloma virus type 11 (HPV-11) DNA in condyloma tissue (abundant target model) and Epstein-Barr virus (EBV) DNA in a mononucleosis lymph node (low target model). For demonstration of HPV-11, all methods gave more or less satisfactory results, which were best with the acid developer solutions. Moreover, for demonstration of EBV DNA, a signal could be obtained only with these developer solutions. Such a method also proved suitable in double immuno-hybrido stainings for the demonstration of EBV DNA in specific antigen-positive Reed-Sternberg cells in paraffin sections of Hodgkin lymph nodes.
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PMID:Application and comparison of silver intensification methods for the diaminobenzidine and diaminobenzidine-nickel endproduct of the peroxidation reaction in immunohistochemistry and in situ hybridization. 153 4

Measurement of the soluble form of CD8 antigen (sCD8), a surface membrane component of suppressor/cytotoxic T cells, has yielded useful information relevant to prognosis in children with acute lymphoblastic leukaemia and Hodgkin's disease (HD). An ELISA technique was used to measure the amount of sCD8 in sera from 123 adults with untreated HD. Significantly higher mean sCD8 levels were found in patients with advanced disease (stage III-IV; P less than 0.001), B-symptoms (P less than 0.001), male sex (P less than 0.05) and increased spontaneous and decreased Concanavalin A induced blood lymphocyte DNA-synthesis (P less than 0.05). Actuarial survival of patients with high sCD8 levels was significantly worse than that of the remainder (P less than 0.05). However, the sCD8 level did not add prognostic information to that achieved by age, sex, lactate dehydrogenase (LDH) or clinical stage. A significant correlation between the sCD8 and LDH levels (r = 0.33; P less than 0.001) and inverse correlations between sCD8 levels and total blood CD4+ (r = -0.52; P less than 0.001) and CD3+ (r = -0.39; P less than 0.01) cell counts were found. Ten patients were also studied in complete remission, showing a significantly reduced sCD8 level in comparison to the pretreatment value (P less than 0.05). Increased sCD8 in HD may indicate enhanced suppressor T cell activity possibly compromising the host disease balance which could explain the association with prognosis.
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PMID:Increased serum CD8 soluble antigen level is associated with blood lymphocyte abnormalities and other established indicators of a poor prognosis in adult Hodgkin's disease. 155 Jul 71

The ability to conveniently detect single-base mutations in the DNA of clinical material without prior knowledge of the mutant sequence remains a diagnostic challenge. Most techniques suffer from a lack of general applicability to all DNA sequences, poor sensitivity, requirement for RNA samples rather than DNA, or necessity for performing DNA sequencing to uncover unknown point mutations. Recently, Montandon, et al. (8) described a novel method whereby segments of DNA amplified by the Polymerase Chain Reaction (PCR) can be rapidly screened for mutations through their formation of heteroduplexes with an end-labeled reference DNA followed by site-specific chemical cleavage at mispaired bases. Here we have applied this PCR-mismatch technique to a portion of the BCL-2 gene, using DNA samples derived from the biopsy specimens of patients with lymphomas or lymphocytic leukemias. The BCL-2 gene becomes activated through a t(14;18) chromosomal translocation in the majority of non-Hodgkin's lymphomas. Somatic point mutations were detected in the BCL-2 genes of 3 of 5 patient samples that contained a t(14;18). No mutations were observed for lymphomas lacking a t(14;18), nor in the DNA of over 20 normal persons. Further analysis excluded the possibility that the detected mutations represented hereditary polymorphisms or PCR-artifacts. Based on comparisons with direct DNA sequencing, the PCR-mismatch technique appeared to be both highly specific and sensitive. The possible mechanisms responsible for these somatic mutations in translocated BCL-2 genes and their functional significance are discussed.
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PMID:Application of a PCR-mismatch technique to the BCL-2 gene: detection of point mutations in BCL-2 genes of malignancies with A t(14,18). 160 14

B-cell associated antigens are frequently expressed by the Reed-Sternberg (RS) cells of lymphocyte predominance (LP) Hodgkin's disease (HD) and are sometimes expressed by those of nodular sclerosis (NS) and mixed cellularity (MC) HD. Clonal immunoglobulin gene rearrangements have been detected in some HD cases as well. These findings suggest that at least some cases of HD may be of B-cell derivation. Rearrangements of the bcl-2 gene, associated with the t(14;18)(q32;q21) are present in more than 75% of follicular and 30% of diffuse lymphomas of B-cell origin, suggesting that this translocation plays an important role in B-cell lymphomagenesis. In this study, we investigated 34 cases of HD (10 LP, 14 NS, and 10 MC) for bcl-2 gene rearrangements to determine if this B-cell lymphoma-associated translocation also plays a role in the pathogenesis of HD. The cases of HD were analyzed by Southern blot hybridization, using DNA probes that detect the major and minor breakpoint cluster regions and a 5'bcl-2 breakpoint region recently cloned and found to be involved in B-cell chronic lymphocytic leukemia, and by the polymerase chain reaction (PCR), using oligonucleotides capable of amplifying and detecting the major breakpoint region (mbr) and minor cluster region (mcr) breakpoint regions in t(14;18). bcl-2 translocations were not detected in any of the 34 cases of HD by Southern blot hybridization or by PCR. This is in spite of the fact that RS cells expressing B-cell-associated antigen CD20 were detectable in 7/8 cases of LP HD and 6/24 cases of NS and MC HD with monoclonal antibody L26. Therefore, these results indicate that the bcl-2 gene translocation does not play an important role in the pathogenesis of HD and did not provide evidence for the B-cell origin of HD.
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PMID:The bcl-2 gene translocation is undetectable in Hodgkin's disease by Southern blot hybridization and polymerase chain reaction. 163 63

Germline p53 mutations have been identified in the Li-Fraumeni syndrome but the role of such mutations in familial leukemia is not established. The p53 gene was examined by single-strand conformation polymorphism analysis of exons 4-8 in 10 families with multiple members affected with leukemia. The diagnoses included acute and chronic leukemias and Hodgkin's disease. Identified in two families were p53 mutations that were nonhereditary. These included a 2-bp deletion in exon 6 found in the lymphoblast DNA of one child whose sibling, cousin, and several adult relatives had acute leukemia. The other nonhereditary p53 mutation was a transition at codon 248 (CGG to CAG, arginine to glutamine) found in the lymphoblasts of a patient with a preleukemic syndrome and acute lymphoblastic leukemia (ALL) whose brother is a long-term survivor of ALL. Thus, p53 mutations were found to occur in two families but both were nonhereditary. Moreover, in the remaining eight families no p53 mutation was identified in the regions of p53 where most mutations have been found in other cancers. Although p53 mutations sometimes may be present, they do not appear to be a primary event responsible for hereditary susceptibility to familial leukemia. This study suggests involvement of other genes or mechanisms.
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PMID:Absence of hereditary p53 mutations in 10 familial leukemia pedigrees. 164 30

Distinction between Hodgkin's disease and peripheral T-cell lymphoma can be difficult, based on routine morphologic and immunohistologic stains. To assess the utility of Southern blot analysis, we investigated the genes for the beta (T beta) and gamma (T gamma) chains of the T-cell antigen receptor and immunoglobin heavy and light chains in 15 unselected cases of Hodgkin's disease. Following digestion with the restriction enzyme EcoRI, the intensity of the germline band corresponding to the first constant region of T beta was reduced when compared with the intensity of the second constant region germline band, a pattern consistent with polyclonal rearrangement of this gene. Hybridization of EcoRI-digested DNA with a probe recognizing the joining regions of T gamma revealed multiple rearranged bands corresponding to the known limited recombinatorial possibilities of this gene. Clonal rearrangement of T beta and T gamma was never demonstrated, although the banding pattern seen with T gamma could easily be misinterpreted as such. The findings in Hodgkin's disease were identical to those obtained in hyperplastic lymph nodes, normal thymuses, and normal peripheral blood enriched for T-cells. We then examined the status of T-cell receptor and immunoglobulin genes in six cases that could not be definitely classified as either Hodgkin's disease or T-cell lymphoma by either morphology or immunohistology. Clonal T-cell receptor gene rearrangement was found in three cases, supporting the diagnosis of T-cell lymphoma. Our study confirms the polyclonal lineage of the major fraction of T-cells and B-cells in Hodgkin's disease, a finding that may have diagnostic importance.
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PMID:Polyclonal rearrangement of the T-cell antigen receptor genes in Hodgkin's disease: implications for diagnosis. 164 54

Cryostat sections from lymph nodes of 47 Hodgkin disease patients were examined by immunohistology for the Epstein-Barr virus (EBV)-encoded latent membrane protein (LMP), nuclear antigen 2, and late viral glycoprotein gp350/250. A distinct LMP-specific membrane and cytoplasmic staining was detected exclusively in Hodgkin and Reed-Sternberg cells in 18 patients (38%); EBV nuclear antigen 2 and gp350/250 immunoreactivity was absent in all instances. Thirty-two of 47 (68%) cases contained EBV-specific DNA sequences as detected by PCR, all LMP-positive cases being in this category. Our results confirm previous studies establishing the presence of EBV genomes in Hodgkin and Reed-Sternberg cells by demonstrating expression of an EBV-encoded protein in the tumor-cell population. The finding of LMP expression in the absence of EBV nuclear antigen 2 suggests a pattern of EBV gene expression different from that of B-lymphoblastoid cell lines and Burkitt lymphoma, whereas this finding shows similarities with that seen in undifferentiated nasopharyngeal carcinoma. Because the LMP gene has transforming potential, our findings support the concept of a pathoetiological role of EBV in many cases of Hodgkin disease.
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PMID:Epstein-Barr virus latent membrane protein expression in Hodgkin and Reed-Sternberg cells. 164 16

Using the monoclonal antibody Ki-67 that detects a cell proliferation-associated human nuclear antigen, incorporations of bromodeoxyuridine (Brud) and 3H-Thymidine, we studied the proliferative capacity of Reed-Sternberg (RS) cells in Hodgkin's cell lines L428, KM-H2, Holden, L540 and L591. The results revealed that in all cell lines, except L591, more than 55% of RS cells were found positive for Ki-67, and over 50% of them had Brud incorporation 5 days after cultivation. The positive score for 3H-Thymidine incorporation was low, and it is assumed that the time taken for 3H-Thymidine in cultivation was short. It shows that at least half of RS cells in these cell lines have proliferation-associated nuclear antigen or can synthesize DNA, and so they are proliferative.
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PMID:[Proliferation of Reed-Sternberg cells in 5 Hodgkin's cell lines]. 164 40


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