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)

Transforming growth factor-beta 1 (TGF-beta 1) is a multifunctional cytokine which promotes fibroblast growth and collagen synthesis, but suppresses growth and differentiation of immune lymphocytes and killer cells. Immunohistochemical detection of TGF-beta 1 in Hodgkin's disease (HD) has been shown to correlate with the histologic feature of nodular sclerosis, which is associated with a favorable prognosis (American Journal of Pathology 1990, 136:1209). In that study, TGF-beta 1 was localized mainly at the margins of broad collagen bands (presumably sites of new collagen synthesis) and in areas containing numerous Hodgkin/Reed-Sternberg cells (H/RS). In these areas, TGF-beta 1 protein was found on the membrane and occasionally within the cytoplasm of H/RS cells. To determine whether TGF-beta 1 is synthesized by H/RS cells or secondarily bound to their membrane and sometimes internalized, we performed in situ hybridization (ISH) using 1.5 Kb 35S-labeled anti-sense and sense RNA probes to TGF-beta 1. Paraffin-embedded tissues of 10 cases from all histologic types of HD were examined. Somewhat unexpectedly, the major site of TGF-beta 1 mRNA was in eosinophils; TGF-beta 1 mRNA was not detected in H/RS cells. TGF-beta 1 mRNA was found in eosinophils in all cases of nodular sclerosis but not in other types of HD, despite the presence of numerous eosinophils in mixed cellularity cases. The presence of TGF-beta 1 mRNA coincided with immunohistochemical detection of TGF-beta 1 protein using antibody CC (1-30). These results confirm the role of TGF-beta 1 in the histogenesis of nodular sclerosing HD and indicate that eosinophils are the major source of TGF-beta 1 in this type of HD.
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PMID:Eosinophils are the major source of transforming growth factor-beta 1 in nodular sclerosing Hodgkin's disease. 842 49

The topography of and the area covered by tenascin, laminin and type IV collagen (all components of the subendothelial basement membrane), and the microvessel area (an index of angiogenesis), as evaluated with factor VIII, were investigated immunohistochemically in 61 B-cell non-Hodgkin's lymphomas (B-NHL) and 30 benign lymphadenopathies as controls. The three components were located in the microvessels and in a microvessel-bound stromal reticular network, the expression of tenascin being always more extended and finer than the other components. Of the lymphadenopathies, reactive and atypical lymphoid hyperplasias showed vessels and stromal network in the interfollicular zone only, whereas in Castleman's and angioimmunoblastic forms these structures were widely scattered in the tissue, and the area of the three components and that of the microvessels were significantly larger. Of the low-grade B-NHL, follicular subtypes had vessels and stromal network confined to the interfollicular inflammatory zone, but not in tumor follicles, whereas these structures were irregularly distributed throughout the small lymphocytic subtype. The levels of areas in low-grade B-NHL overlapped those of Castleman's and angioimmunoblastic lymphadenopathies. Among the intermediate-grade tumors, the follicular subtype resembled the follicular tumors, and the diffuse subtypes displayed vessels and stromal network throughout the tissue in close association with the neoplastic cells, and with significant increments of both the tenascin and the microvessel areas, but with a significant reduction of both the laminin and the type IV collagen areas. Distribution was similar in high-grade B-NHL, but tenascin and microvessel area variations, on the one hand, and those of laminin and type IV collagen areas were still more apparent than in the intermediate-grade. A high correlation was demonstrated in all groups of tissues between tenascin and microvessel area. In addition, in the diffuse intermediate-grade and high-grade B-NHL highly immature vessels were frequently detected by ultramicroscopy. The results show that tenascin expression and angiogenesis are closely related, and that both increase in function of tumor malignancy. Unlike laminin and type IV collagen, tenascin is associated with highly immature vessels in B-NHL. We suggest that tenascin expression and angiogenesis are governed by the B-NHL-associated inflammatory infiltrate, as well as by the B-NHL cells, particularly in more malignant tumors.
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PMID:Expression of tenascin is related to histologic malignancy and angiogenesis in b-cell non-Hodgkin's lymphomas. 888 61

Hepatocyte growth factor (HGF)/scatter factor (SF) is the ligand for a tyrosine kinase cell surface receptor encoded by the MET protooncogene (c-MET). HGF/SF can induce proliferation and motility in epithelial cells and promotes invasion of carcinoma cells and NIH3T3 fibroblasts transfected with both HGF/SF and c-MET genes. Our results show that HGF/ SF and c-MET also play a role in adhesion and invasion of human lymphoma cells. c-MET mRNA is expressed in hemopoietic cells, such as hemopoietic progenitor cells (CD34+ cells) in bone marrow (BM) and mobilized peripheral blood, immature B cells in cord blood and BM, and germinal center B-centroblasts. In normal peripheral blood B cells, which are c-MET-, c-MET expression was induced by PMA, ConA, HGF/ SF, and Epstein-Barr virus (EBV) infection. Using immunohistochemistry, we detected c-MET on the cell surface of large activated centroblasts in lymph nodes from patients with B-non-Hodgkin's lymphoma and Hodgkin's disease. In the latter group, c-MET expression correlated well with the presence of EBV. Because HGF/SF and c-MET promote metastasis of carcinoma cells, we studied the effects of c-MET stimulation by HGF/SF of B-lymphoma cells on properties relevant for metastasis, ie, adhesion, migration, and invasion. HGF/SF stimulated adhesion of the c-MET+ B-cell lines to the extracellular matrix molecules fibronectin (FN) and collagen (CN) in a dose dependent manner. However, adhesion to laminin was not affected by HGF/SF. Adhesion to FN was mediated by beta 1-integrins alpha 4 beta 1 (VLA4) and alpha 5 beta 1 (VLA5) since blocking antibodies against beta 1- (CD29), alpha 4-(CD49d), or alpha 5- (CD49e) integrin subunits, completely reversed the effect of HGF/SF. Furthermore, HGF/SF induced adhesion was abrogated by addition of genistein, which blocks protein tyrosine kinases, including c-MET. Addition of HGF/SF resulted in a sixfold increase in migration of c-MET B-lymphoma cells through Matrigel, compared to medium alone. In rat fibroblast cultures, HGF/SF doubled the number of c-MET+ B-lymphoma cells that invaded the fibroblast monolayer. In these adhesion, migration and invasion assays HGF/SF had no effect on c-MET- cell lines. In conclusion, c-MET is expressed or can be induced on immature, activated, and certain malignant B cells. HGF/SF increased adhesion of c-MET+ B-lymphoma cells to FN and CN, mediated via beta 1-integrins alpha 4 beta 1 and alpha 5 beta 1, and furthermore promoted migration and invasion.
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PMID:Hepatocyte growth factor/scatter factor promotes adhesion of lymphoma cells to extracellular matrix molecules via alpha 4 beta 1 and alpha 5 beta 1 integrins. 902 31

CD44 is a ubiquitous multistructural and multifunctional cells surface adhesion molecule involved in cell-cell and cell-matrix interactions. Twenty exons are involved in the genomic organization of this molecule. The first five and the last 5 exons are constant, whereas the 10 exons located between these regions are subjected to alternative splicing, resulting in the generation of a variable region. Differential utilization of the 10 variable region exons, as well as variations in N-glycosylation, O-glycosylation, and glycosaminoglycanation (by heparan sulfate or chondroitin sulfate), generate multiple isoforms (at least 20 are known) of different molecular sizes (85-230 kDa). The smallest CD44 molecule (85-95 kDa), which lacks the entire variable region, is standard CD44 (CD44s). As it is expressed mainly on cells of lymphohematopoietic origin, CD44s is also known as hematopoietic CD44 (CD44H). CD44s is a single-chain molecule composed of a distal extracellular domain (containing, the ligand-binding sites), a membrane-proximal region, a transmembrane-spanning domain, and a cytoplasmic tail. The molecular sequence (with the exception of the membrane-proximal region) displays high interspecies homology. After immunological activation, T lymphocytes and other leukocytes transiently upregulate CD44 isoforms expressing variant exons (designated CD44v). A CD44 isform containing the last 3 exon products of the variable region (CD44V8-10, also known as epithelial CD44 or CD44E), is preferentially expressed on epithelial cells. The longest CD44 isoform expressing in tandem eight exons of the variable region (CD44V3-10) was detected in keratinocytes. Hyaluronic acid (HA), an important component of the extracellular matrix (ECM), is the principal, but by no means the only, ligand of CD44. Other CD44 ligands include the ECM components collagen, fibronectin, laminin, and chondroitin sulfate. Mucosal addressin, serglycin, osteopontin, and the class II invariant chain (Ii) are additional, ECM-unrelated, ligands of the molecule. In many, but not in all cases, CD44 does not bind HA unless it is stimulated by phorbol esters, activated by agonistic anti-CD44 antibody, or deglycosylated (e.g., by tunicamycin). CD44 is a multifunctional receptor involved in cell-cell and cell-ECM interactions, cell traffic, lymph node homing, presentation of chemokines and growth factors to traveling cells, and transmission of growth signals. CD44 also participates in the uptake and intracellular degradation of HA, as well as in transmission of signals mediating hematopoiesis and apoptosis. Many cancer cell types as well as their metastases express high levels of CD44. Whereas some tumors, such as gliomas, exclusively express standard CD44, other neoplasms, including gastrointestinal cancer, bladder cancer, uterine cervical cancer, breast cancer and non-Hodgkin's lymphomas, also express CD44 variants. Hence CD44, particularly its variants, may be used as diagnostic or prognostic markers of at least some human malignant diseases. Furthermore, it has been shown in animal models that injection of reagents interfering with CD44-ligand interaction (e.g., CD44s- or CD44v-specific antibodies) inhibit local tumor growth and metastatic spread. These findings suggest that CD44 may confer a growth advantage on some neoplastic cells and, therefore, could be used as a target for cancer therapy. It is hoped that identification of CD44 variants expressed on cancer but not on normal cells will lead to the development of anti-CD44 reagents restricted to the neoplastic growth.
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PMID:CD44: structure, function, and association with the malignant process. 911 68

Nine well-differentiated liposarcomas with foci simulating the appearance of malignant lymphoma and other lymphoid disorders are reported. Their clinical presentation and evolution were not significantly different from those of their conventional counterparts lacking a lymphoid infiltrate. Microscopically, these tumors were characterized by areas of ordinary well-differentiated liposarcoma, admixed with discrete nodules comprised of small germinal centers, and separated by an admixture of lymphocytes, spindled stromal cells, collagen, and blood vessels, in which highly atypical tumor cells were embedded. The differential diagnosis included Hodgkin's disease, Castleman's disease, and inflammatory pseudotumor. Immunohistochemical evaluation revealed a pre-dominance of T cells in the lymphocytic population. Molecular genetic studies revealed no evidence of clonal rearrangement of the T cell receptor gene, supporting the interpretation of these lymphocytes as reactive. Awareness of the existence of this variant of inflammatory liposarcoma should prevent its misinterpretation as a primary lymphoproliferative process.
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PMID:Lymphocyte-rich well-differentiated liposarcoma: report of nine cases. 925 51

Thirty-nine freeze-dried tissue samples from 17 lymphoid tumors (nine malignant non-Hodgkin's lymphomas) were studied by Fourier transform infrared (FTIR) spectroscopy. The absorbance ratio A1121/A1020 increased, along with the emergence of an absorbance pulse at 1121 cm-1, with increasing clinicopathological grade of malignant lymphoma. An increasing A1121/A1020 ratio from benign to malignant is evident in literature spectra from several different tissues; however, the present study is the first to comment on this effect and to propose it as an index of the cellular RNA/DNA ratio after subtraction of overlapping absorbances, if present, due to collagen or glycogen. Absorbance attributable to collagen increased with lymphoma grade and was greater in benign inflammatory tumors than in low-grade lymphomas. The A1121/A1020 trend observed here may form the basis of a universal cancer-grading parameter to assist with cancer treatment decisions and may also be useful in the analysis of cellular growth perturbation induced by drugs or other therapies. Our spectral findings may potentially be applied to cell clusters and discrete areas of tumor tissue sections using the FTIR microscope, allowing correlation with morphology and a high degree of spatial resolution.
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PMID:Cancer grading by Fourier transform infrared spectroscopy. 954 13

ESR is a time-honored, simple, inexpensive test, but unfortunately it lacks sensitivity and specificity. Clinicians need to be aware of appropriate uses, because any test is expensive when ordered often, and evaluation of false-positive results may incur substantial costs and place the patient at risk from additional procedures. ESR should not be used to screen asymptomatic persons for disease. If an increased ESR is encountered and no explanation is immediately apparent, clinicians should repeat the test in several months rather than pursue an exhaustive search for occult disease. ESR may be useful in establishing a "sickness index" in elderly persons who have nonspecific changes in health status and a moderate probability of underlying disease; in screening for infection in specific settings (e.g., orthopedic surgery, pediatrics, gynecology); in diagnosing and monitoring temporal arteritis, polymyalgia rheumatica, and possibly other rheumatic diseases; in monitoring patients with treated Hodgkin's disease; and in assessing iron deficiency in anemia of chronic disease (when correlated with serum ferritin level). An ESR value exceeding 100 mm/hr has a 90% predictive value for serious underlying disease, most often infection, collagen vascular disease, or metastatic tumor. In asymptomatic persons with a markedly elevated ESR value, a minimal number of tests usually reveal the cause.
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PMID:The erythrocyte sedimentation rate. Still a helpful test when used judiciously. 959 Sep 99

A 47 years old female, treated in 1984 for a non Hodgkin lymphoma, presented in 1993 with diarrhea with features of steatorrhea. The initial assessment concluded that the patient had a gluten induced enteropathy and she had a good clinical response to a gluten free diet. In 1996, while still on gluten free diet, steatorrhea appeared. A new intestinal biopsy showed sub epithelial collagen deposition. After an empiric treatment with prednisone and sulphasalazine, steatorrhea abated but subepithelial collagen deposition persisted in intestinal biopsies.
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PMID:[Collagenous sprue. Clinical case]. 992 14

Syndecan-1 is a transmembrane proteoglycan expressed on the surface of tumor cells of various origins including myeloma, Hodgkin's disease, and certain human immunodeficiency virus (HIV) associated lymphomas. Functional studies in myeloma reveal that syndecan-1 may act as a multifunctional regulator of cell behavior in the tumor microenvironment; it mediates cell-cell adhesion, binding of myeloma cells to type I collagen, and inhibits tumor cell invasion into collagen gels. In addition, syndecan-1 is released from the surface of myeloma cells and this shed form of the molecule inhibits growth and induces apoptosis of myeloma cells and may modulate myeloma bone disease by inhibiting osteoclast formation and promoting osteoblast formation. In view of its effects on tumor cell growth, survival, adhesion and invasion and on bone cell differentiation, syndecan-1 may be an important potentially beneficial regulator of myeloma pathobiology. Further studies are needed to define the clinical significance of syndecan-1 in myeloma and to examine its functional significance in other lymphoid malignancies.
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PMID:Syndecan-1 (CD 138) in myeloma and lymphoid malignancies: a multifunctional regulator of cell behavior within the tumor microenvironment. 1035 Mar 30

Kikuchi's disease (KD) is an idiopathic, self-limited necrotizing lymphadenitis that can clinically and histologically mimic high-grade lymphoma, including Hodgkin's disease, or can be mistaken for the lymphadenitis of systemic lupus erythematosus (SLE). Involvement of extranodal sites is unusual but well documented, especially in Asia, where KD is more common than in North America or Europe. The successful distinction of KD from malignant lymphoma and SLE is imperative for the appropriate treatment of affected patients. We describe five patients with cutaneous involvement by KD, all of whom presented with fever, lymphadenopathy, and an eruption on the skin of the upper body, which in one case was clinically suspected to be due to SLE and in another, polymorphous light eruption. The patients ranged in age from 10 months to 42 years (median, 33 years) and included three females and two males. All five patients had negative serologic studies for collagen vascular disease. Each patient had a lymph node biopsy showing the typical necrotizing lymphadenitis of KD. Skin biopsies from all five patients shared a specific constellation of histologic features: vacuolar interface change with necrotic keratinocytes, a dense lymphohistiocytic superficial and deep perivascular and interstitial infiltrate, varying amounts of papillary dermal edema, and abundant karyorrhectic debris with a conspicuous absence of neutrophils and a paucity of plasma cells, paralleling the nodal histology in KD. CD68 immunohistochemistry on paraffin-embedded sections showed many histiocytes and plasmacytoid monocytes in all cases, whereas CD3, CD4, and CD8 showed highly variable staining among the cases. There was only rare staining with TIA-1 and CD30. We believe that the papular eruption of KD has recognizable histopathologic features and that a CD68 stain that marks many cells that initially seem to be lymphocytes can be performed to confirm the diagnosis.
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PMID:The histopathology of cutaneous lesions of Kikuchi's disease (necrotizing lymphadenitis): a report of five cases. 1047 63


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