Search

To analyze the role of nonacid reflux in laryngopharyngeal reflux diseases (LPRD). From January 2014 to April 2019, 344 patients associated with LPRD underwent 24-h multichannel intraluminal impedance–pH monitoring, and their reflux symptom index (RSI) and reflux finding score (RFS) were recorded. The numbers of acid, weakly acidic and alkaline reflux events in the laryngopharynx were counted, and the consistency analysis of the results with the results of the RSI and RFS was conducted. Among the 344 patients, nonacid reflux events accounted for 74.1% (1367/1845) of the all reflux events. There were 111 patients with ≥ 3 acid reflux events, 218 patients with ≥ 3 any kinds of reflux events, and 257 patients with positive results of RSI or RFS. Taking the results of the RSI and or RFS as a reference, the sensitivity, specificity and consistency test Kappa value for the diagnosis of LPRD according to the existence of ≥ 3 acid reflux events were 41.2%, 94.2% and 0.228, respectively. With the existence of three or more all kinds of reflux events as the standard, the sensitivity, specificity and consistency test Kappa value were 76.7%, 74.7% and 0.449, respectively. The nonacid reflux events account for the highest proportion of laryngopharyngeal reflux events, and the consistency of the results of RSI and or RFS with all reflux events is higher than that with only acid reflux events, that indicates nonacid reflux may play an important role in LPRD.

Human herpesvirus-8 (HHV-8) has been detected in Kaposi's sarcoma (KS) lesions of all types (AIDS-related, classical and endemic), in body-cavity-based B-cell lymphomas (BCBLs) and in le-sions of multicentric Castleman's disease (MCD). We have identified a major gamma-herpesvirus-divergent locus (DL-B) in HHV-8 DNA encoding several HHV-8 unique open reading frames (ORFs), including a homologue of interleukin-6 (IL-6) and two homologues of macrophage inflammatory protein MIP-1. We show that the HHV-8-encoded IL-6 homologue (vlL-6) shares functional properties with endogenous IL-6 proteins and that both vlL-6 and vMIP-1 transcripts are present at high levels following butyrate induction of an HHV-8+ BCBL cell line. Low amounts of constitutive vlL-6, but not vMIP-1, mRNA were also detected. The presence of a functional IL-6 homologue encoded by HHV-8 may provide a mechanistic model for the hypothesized role of HHV-8 in KS, MCD and BCBL that involves the mitogenic effects of vlL-6 on surrounding cells. MIP-1 proteins may enhance these effects through the chemotactic recruitment of endogenous cy-tokine-producing cells into affected tissues and could potentially influence HIV disease progression in coinfected individuals through interactions with the HIV co-receptor CCR-5.

Human herpesvirus 8 (HHV-8) is a recently discovered virus that is highly associated with Kaposi's sarcoma (KS) and AIDS-associated body cavity lymphomas, although it is also found in some normal individuals. HHV-8 is related by nucleotide sequence homology to herpesvirus saimiri (HVS), which causes T cell lymphomas in some New World monkeys, and to Epstein–Barr virus (EBV), a human herpesvirus linked etiologically with Burkitt's lymphoma and nasopharyngeal carcinoma. We report that, like HVS but unlike EBV, HHV-8 contains a gene (ORF74) with significant sequence homology to the high-affinity IL-8 receptor, a member of the α (CXC) chemokine receptor family of transmembrane G protein-coupled receptors. We also show by reverse transcription PCR that the chemokine receptor-related HHV-8 gene is detectable in some RNA samples from KS tissue, and that its expression varies independently from that of ORF26, a minor capsid protein. The presence of a potential chemokine receptor in HHV-8 and its expression in KS tissue suggests that it may be important in the regulation of viral gene expression and may play a role in the etiology of KS and AIDS-related body cavity lymphomas.

The product of human herpesvirus 8 (HHV-8) open reading frame 74 (ORF74) is related structurally and functionally to cellular chemokine receptors. ORF74 activates several cellular signaling pathways in the absence of added ligands, and NIH 3T3 cells expressing ORF74 are tumorigenic in nude mice. We have generated a line of transgenic (Tg) mice with ORF74 driven by the simian virus 40 early promoter. A minority (approximately 30%) of the Tg mice, including the founder, developed tumors resembling Kaposi's sarcoma (KS) lesions, which occurred most typically on the tail or legs. The tumors were highly vascularized, had a spindle cell component, expressed VEGF-C mRNA, and contained a majority of CD31 + cells. CD31 and VEGF-C are typically expressed in KS. Tumors generally (but not always) occurred at single sites and most were relatively indolent, although several mice developed large visceral tumors. ORF74 was expressed in a minority of cells in the Tg tumors and in a few other tissues of mice with tumors; mice without tumors did not express detectable ORF74 in any tissues tested. Cell lines established from tumors expressed ORF74 in a majority of cells, expressed VEGF-C mRNA, and were tumorigenic in nude mice. The resultant tumors grew rapidly, metastasized, and continued to express ORF74. Cell lines established from these secondary tumors also expressed ORF74 and were tumorigenic. These data strongly suggest that ORF74 plays a role in the pathology of KS and confirm and extend previous findings on the tumorigenic potential of ORF74.

Infection with human herpesvirus 8 (HHV-8), also known as Kaposi's sarcoma (KS)-associated herpesvirus, is necessary for the development of KS. The HHV-8 lytic-phase gene ORF74 is related to G protein-coupled receptors, particularly interleukin-8 (IL-8) receptors. ORF74 activates the inositol phosphate/phospholipase C pathway and the downstream mitogen-activated protein kinases, JNK/SAPK and p38. We show here that ORF74 also activates NF-κB independent of ligand when expressed in KS-derived HHV-8-negative endothelial cells or primary vascular endothelial cells. NF-κB activation was enhanced by the chemokine GROα, but not by IL-8. Mutation of Val to Asp in the ORF74 second cytoplasmic loop did not affect ligand-independent signaling activity, but it greatly increased the response to GROα. ORF74 upregulated the expression of NF-κB-dependent inflammatory cytokines (RANTES, IL-6, IL-8, and granulocyte-macrophage colony-stimulating factor) and adhesion molecules (VCAM-1, ICAM-1, and E-selectin). Supernatants from transfected KS cells activated NF-κB signaling in untransfected cells and elicited the chemotaxis of monocytoid and T-lymphoid cells. Expression of ORF74 conferred on primary endothelial cells a morphology that was strikingly similar to that of spindle cells present in KS lesions. Taken together, these data, demonstrating that ORF74 activates NF-κB and induces the expression of proangiogenic and proinflammatory factors, suggest that expression of ORF74 in a minority of cells in KS lesions could influence uninfected cells or latently infected cells via autocrine and paracrine mechanisms, thereby contributing to KS pathogenesis.

Background Human herpesvirus 8 (HHV-8) DNA sequences have been detected in Kaposi's sarcoma, in primary effusion lymphoma (an unusual high-grade non-Hodgkin's lymphoma seen primarily in patients with acquired immunodeficiency syndrome [AIDS]), and in Castleman's disease (a rare lymphoproliferative disorder); however, proof that HHV-8 is involved in the pathogenesis of these diseases remains to be established. HHV-8 contains a gene, i.e., v-cyclin D, that is a homologue of the cellular cyclin D2 gene, which encodes a protein that promotes passage through G1 phase of the cell cycle. Previous studies have identified v-cyclin D messenger RNA (mRNA) in biopsy specimens of Kaposi's sarcoma. In this study, we isolated a full-length v-cyclin D complementary DNA and characterized the pattern of v-cyclin D mRNA expression in Kaposi's sarcoma. Methods Standard methods were used to construct and to screen HHV-8 genomic and complementary DNA libraries. Reverse transcription-polymerase chain reaction (RT-PCR) methods and in situ hybridization with RNA probes were used to examine v-cyclin D mRNA expression. Results RT-PCR demonstrated the presence of v-cyclin D mRNA in biopsy specimens of AIDS-related Kaposi's sarcoma, in early-passage spindle cells from classical (i.e., not AIDS-related) Kaposi's sarcoma, and in spindle cells isolated from the peripheral blood of patients with AIDS-related Kaposi's sarcoma. In situ hybridization indicated that mRNAs for v-cyclin D and kaposin, an HHV-8 latency-associated gene, were present in approximately 1% of the spindle cells in early patch lesions and approximately 60% of the spindle cells in late nodular lesions of Kaposi's sarcoma. Conclusions Spindle cells of Kaposi's sarcoma, which have been regarded as the tumor cells of this cancer, contain v-cyclin D mRNA. Expression of v-cyclin D protein may be involved in the pathogenesis of Kaposi's sarcoma by promoting cell proliferation.

Antibodies reactive with proteins of human T-cell leukemia virus (HTLV) can be found in Old World monkeys. A T-lymphocyte cell line established from a seropositive baboon (Papio cynocephalus) was analyzed for the presence of viral DNA sequences. The provirus found in these cells was related to but distinct from HTLV subgroup I. These results add to recent evidence from human studies that HTLV represents a spectrum of infectious T-lymphotropic retroviruses that includes closely and distantly related members.

The isolation from macaques of retroviruses related to human immunodeficiency virus (HIV) led to the identification of a second group of human retroviruses (termed HIV-2), which are prevalent in West Africa and closely related to the simian immunodeficiency virus (SIV). We have cloned and determined the complete nucleotide sequence of the human West African retrovirus HIV-2NIH-Z and compared it to that of a previously described strain of HIV-2 (HIV-2ROD) as well as to SIV and HIV-1. We have reached the following conclusions: (i) The HIV-2 isolates are (slightly) more closely related to each other than to SIV, compatible with their isolation from different species. (ii) The variability between HIV-2 isolates is similar in degree and kind to that found among HIV-1 isolates. The equivalent degrees of intragroup divergence suggest that HIV-1 and HIV-2 have existed in their present ranges in Africa for approximately equal lengths of time. The fact that acquired immunodeficiency syndrome is widespread in regions where HIV-1 is prevalent but not in regions where HIV-2 is prevalent suggests a substantial difference in the morbidity rates associated with HIV-1 vs. HIV-2 infection. (iii) HIV-2 and SIV are related to each other more closely than they are to HIV-1.