Kaposi's sarcoma (KS) appears to develop in association with kidney transplantation, but unlikely with dialysis. We report two cases of classic KS that occurred in patients receiving short-term (less than 3 yr) dialysis. They have been suffering from chronic renal failure due to tuberculosis and diabetes mellitus, respectively. Several to multiple, reddened-violaceous patches, plaques and nodules were found on the hand and the lower extremities. Laboratory studies showed no evidence suggesting immunosuppressed state and there was no history of taking immunosuppressive agents. The biopsies of the two cases revealed proliferation of spindle-shaped cells focally arranged in bundles and multiple dilated vascular spaces outlined by an attenuated endothelium with intravascular and extravasated erythrocytes. The specimens expressed positivity with CD34 antigen. Human herpesvirus 8 (Kaposi's sarcoma-associated herpesvirus) was detected in one case by polymerase chain reaction method.
Aged ; Case Report ; Herpesvirus, Kaposi Sarcoma-Associated/isolation & purification ; Human ; Kidney Transplantation/adverse effects ; Male ; Middle Age ; Renal Dialysis/adverse effects* ; Sarcoma, Kaposi/virology ; Sarcoma, Kaposi/therapy ; Sarcoma, Kaposi/etiology*

Aged ; Female ; Herpesvirus 8, Human ; isolation & purification ; Humans ; Immunosuppressive Agents ; adverse effects ; Pemphigoid, Bullous ; complications ; Sarcoma, Kaposi ; virology

Adult ; Blood Donors ; China ; epidemiology ; Female ; Herpesviridae Infections ; epidemiology ; transmission ; Herpesvirus 8, Human ; Humans ; Male ; Sarcoma, Kaposi ; epidemiology ; virology ; Substance Abuse, Intravenous ; virology

Increased incidences of Kaposi's sarcoma and lymphoid malignancies have been observed in patients with pemphigus, and the human herpesvirus 8 (HHV-8) is very strongly associated with these tumors. Because the virus may be one of the triggering factors of pemphigus, we undertook this study to screen for the presence of HHV-8 in chronic blistering skin diseases including pemphigus. A total of 45 paraffin-embedded specimens were studied using nested polymerase chain reaction (PCR) with primers to amplify a 160-base pair HHV-8 fragment. HHV-8 DNA could be detected in 7 of 9 patients with pemphigus vulagris, and 1 of 2 with pemphigus foliaceus. All specimens of other blistering skin diseases were negative for HHV-8. On sequencing PCR products, the sequences were almost identical with the prototypic sequence for HHV-8, and a few base- pair substitutions at 1086C-T and 1139A-C were detected. The results of our study suggests that HHV-8 might have trophism for pemphigus lesions. Further studies including comparison of HHV-8 DNA load in both lesional and normal skin in the same patient, serological and animal studies would be helpful to study the relationship between HHV-8 and pemphigus.
Adult ; Comparative Study ; DNA Mutational Analysis ; DNA, Viral/genetics ; DNA, Viral/analysis+ACo- ; Female ; Herpesviridae Infections/virology+ACo- ; Herpesviridae Infections/epidemiology ; Herpesvirus, Kaposi Sarcoma-Associated/pathogenicity ; Herpesvirus, Kaposi Sarcoma-Associated/isolation +ACY- purification+ACo- ; Herpesvirus, Kaposi Sarcoma-Associated/genetics ; Human ; Korea/epidemiology ; Male ; Middle Age ; Paraffin Embedding ; Pemphigus/virology+ACo- ; Pemphigus/etiology ; Polymerase Chain Reaction ; Prevalence ; Retrospective Studies ; Skin Diseases, Vesiculobullous/virology+ACo- ; Skin Diseases, Viral/virology+ACo- ; Skin Diseases, Viral/epidemiology ; Tissue Fixation

Increased incidences of Kaposi's sarcoma and lymphoid malignancies have been observed in patients with pemphigus, and the human herpesvirus 8 (HHV-8) is very strongly associated with these tumors. Because the virus may be one of the triggering factors of pemphigus, we undertook this study to screen for the presence of HHV-8 in chronic blistering skin diseases including pemphigus. A total of 45 paraffin-embedded specimens were studied using nested polymerase chain reaction (PCR) with primers to amplify a 160-base pair HHV-8 fragment. HHV-8 DNA could be detected in 7 of 9 patients with pemphigus vulagris, and 1 of 2 with pemphigus foliaceus. All specimens of other blistering skin diseases were negative for HHV-8. On sequencing PCR products, the sequences were almost identical with the prototypic sequence for HHV-8, and a few base- pair substitutions at 1086C-T and 1139A-C were detected. The results of our study suggests that HHV-8 might have trophism for pemphigus lesions. Further studies including comparison of HHV-8 DNA load in both lesional and normal skin in the same patient, serological and animal studies would be helpful to study the relationship between HHV-8 and pemphigus.
Adult ; Comparative Study ; DNA Mutational Analysis ; DNA, Viral/genetics ; DNA, Viral/analysis+ACo- ; Female ; Herpesviridae Infections/virology+ACo- ; Herpesviridae Infections/epidemiology ; Herpesvirus, Kaposi Sarcoma-Associated/pathogenicity ; Herpesvirus, Kaposi Sarcoma-Associated/isolation +ACY- purification+ACo- ; Herpesvirus, Kaposi Sarcoma-Associated/genetics ; Human ; Korea/epidemiology ; Male ; Middle Age ; Paraffin Embedding ; Pemphigus/virology+ACo- ; Pemphigus/etiology ; Polymerase Chain Reaction ; Prevalence ; Retrospective Studies ; Skin Diseases, Vesiculobullous/virology+ACo- ; Skin Diseases, Viral/virology+ACo- ; Skin Diseases, Viral/epidemiology ; Tissue Fixation

OBJECTIVETo study the relationship between Kaposi's sarcoma (KS) and human herpes virus 8 (HHV8; Kaposi's sarcoma-associated herpes virus), and to develop an in situ hybridization (ISH) technique effective for clinical pathological diagnosis.

METHODSPolymerase chain reaction (PCR) technique was used to synthesize a digoxigenin-labeled single stranded DNA probe specific for HHV8 open reading frame 72 cyclin D homolog gene encoded mRNA as the probe accompanying with a tyramide signal amplification system (TSA) for ISH assay. Totally 20 formalin-fixed and paraffin-embedded samples from 14 cases of KS from Danish patients were collected for HHV8 detection. In order to compare the result obtained, all of these cases were checked simultaneously using PCR technique.

RESULTSHHV8 was detected in 10 of 14 (71%) KS cases, of which 8 cases were positive for HHV8 by both ISH and PCR. In ISH, HHV8 hybridization signal was seen as a dot or patch located in the nuclei of both the neoplastic spindle cells and the endothelial cells. HHV8 was found in lesions in all the stages of KS including early patch, plaque and late nodular or tumor lesions, as well as in the primary and metastatic lesions. All the control cases showed a relevant positive or negative results.

CONCLUSIONSThe results further confirmed that there is a strong association between Kaposi's sarcoma and HHV8. The ISH technique with single stranded probe and TSA would be helpful in clinical pathological diagnosis for HHV8 infected diseases, such as KS, primary effusion lymphoma and multicentric Castleman's disease.

Adolescent ; Adult ; Female ; Herpesvirus 8, Human ; isolation & purification ; Humans ; In Situ Hybridization ; methods ; Male ; Middle Aged ; Polymerase Chain Reaction ; methods ; Sarcoma, Kaposi ; pathology ; virology ; Tyramine

Acquired Immunodeficiency Syndrome ; complications ; pathology ; Antigens, CD34 ; metabolism ; Gastrectomy ; methods ; Humans ; Male ; Middle Aged ; Sarcoma, Kaposi ; metabolism ; pathology ; surgery ; virology ; Stomach ; pathology ; Stomach Neoplasms ; metabolism ; pathology ; surgery ; virology ; Vimentin ; metabolism

Viral proteins of gamma-2 herpesviruses, such as LMP2A of Epstein Barr virus (EBV) and Tip of herpesvirus saimiri (HVS) dysregulate lymphocyte signaling by interacting with Src family kinases. K15 open reading frame of Kaposi's sarcoma associated herpesvirus (KSHV), located at the right end of the viral genome, encodes several splicing variants differing in numbers of transmembrane domains. Previously, we demonstrated that the cytoplasmic tail of the K15 protein interfered with B cell receptor signal transduction to cellular tyrosine phosphorylation and calcium mobilization. However, the detailed mechanism underlying this phenomenon was not understood. In the C-terminal cytoplasmic region of K15, putative binding domains for Src-SH2 and -SH3 were identified. In this study, we attempted to characterize these modular elements and cellular binding protein(s) by GST pull down and co-immunoprecipitation assays. These studies revealed that K15 interacted with the major B cell tyrosine kinase Lyn. In vitro kinase and transient co-expression assays showed that the expression of K15 protein resulted in activation of Lyn kinase activity. In addition, GST pull down assay suggested that the SH2 domain of Lyn alone was necessary for interaction with the C-terminal SH2B (YEEV) of K15, but the addition of Lyn SH3 to the SH2 domain increases the binding affinity to K15 protein. The data from luciferase assays indicate that K15 expression in BJAB cells induced NFAT and AP1 activities. The tyrosine residue in the C-terminal end of K15 required for the Lyn interaction appeared to be essential for NFAT/AP1 activation, highlighting the significance of the C-terminal SH2B of K15 as a modular element in interfering with B lymphocyte signaling through interaction with Lyn kinase.
Cell Line ; Herpesvirus 8, Human/genetics/*metabolism ; Humans ; Immunoblotting ; Immunoprecipitation ; Membrane Proteins/genetics/*metabolism ; NFATC Transcription Factors/genetics/*metabolism ; Phosphorylation ; Protein Binding ; Sarcoma, Kaposi/virology ; Transcription Factor AP-1/genetics/*metabolism ; Transfection ; Viral Proteins/genetics/*metabolism ; src-Family Kinases/genetics/*metabolism

Castleman's disease represents an atypical lymphoproliferative disorder, infrequently associated with various immunologic abnormalities or subsequent development of malignancy such as Kaposi sarcoma, malignant lymphoma and plasmacytoma. Its clinicopathologic features depend on various etiologic factors such as Kaposi sarcoma herpesvirus (KSHV), oversecretion of IL-6, adhesion molecule and follicular dendritic cell dysplasia, etc. To investigate the relationship of Castleman's disease (CD) and the above factors, we reviewed 22 cases of CD. Four cases of KSHV positive CD were detected, all multicentric, plasma cell type, and these cases displayed prominent vascular proliferation, characteristic 'Kaposi-like lesion'. IL-6 and CD54 positive mononuclear cells were scattered in interfollicular areas of KSHV positive cases. Follicular dendritic cell hyperplasia, vascular proliferation, expression of IL-6 and CD54 did not show any significant difference between solitary vs multicentric type, and plasma cell type vs hyaline vascular type. Our study suggests that KSHV positive CD reveals unique pathologic features, and the probable relationship of KSHV and IL-6 and CD54 is discussed.
Adolescence ; Adult ; Biological Markers ; Dendritic Cells, Follicular/pathology ; Epstein-Barr Virus Infections/virology ; Epstein-Barr Virus Infections/epidemiology ; Female ; Germinal Center/pathology ; Giant Lymph Node Hyperplasia/virology ; Giant Lymph Node Hyperplasia/pathology+ACo- ; Giant Lymph Node Hyperplasia/epidemiology ; Giant Lymph Node Hyperplasia/classification ; Herpesviridae Infections/virology ; Herpesviridae Infections/epidemiology ; Herpesvirus 4, Human/isolation +ACY- purification ; Herpesvirus, Kaposi Sarcoma-Associated/isolation +ACY- purification ; Human ; Hyperplasia ; Intercellular Adhesion Molecule-1/analysis ; Interleukin-6/analysis ; Korea/epidemiology ; Lymph Nodes/virology ; Lymph Nodes/pathology ; Lymph Nodes/chemistry ; Male ; Middle Age ; Neovascularization, Pathologic ; Receptors, Complement 3d/analysis ; Retrospective Studies ; Tumor Virus Infections/virology ; Tumor Virus Infections/epidemiology