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The World Health Organization classification of malignant lymphoma: incidence and clinical prognosis in HTLV-1-endemic area of Fukuoka.

New insights into the pathogenesis of lymphoid malignancies have been gained through novel genetic, molecular and immunological techniques. A new classification system for lymphoid malignancies, known as the new World Health Organization (WHO) classification, has been proposed recently based on these findings. The relative incidence of the subtypes of malignant lymphoma is known to differ according to geographic location. Adult T-cell leukemia/lymphoma (ATLL) is a human malignancy associated with human T-cell leukemia virus type 1 (HTLV-1), and the Kyushu islands are an HTLV-1 endemic area. To clarify the relationship between the histological classification and prognosis of lymphoid malignancies, we reclassified previous cases in our department and summarized our previous reports using the WHO classification. Of 933 cases of lymphoid malignancies, 471 (50%) were B-cell lymphoma, 396 (42%) T/natural killer (NK)-cell lymphoma and 41 (4%) Hodgkin lymphoma (HL). Analysis of clinical outcome showed favorable prognosis for HL, intermediate for B-cell lymphoma and poor prognosis for T-cell lymphoma. Among B-cell lymphomas, the commonest type was diffuse large B-cell lymphoma (n = 281; 60%). Marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) was diagnosed in 82 cases (17%), follicular lymphoma in 52 (11%) and mantle cell lymphoma in 24 (5%). Other less common lymphomas were Burkitt lymphoma (n = 9; 2%) and lymphoblastic lymphoma (n = 5; 1%). Using overall survival rates, the various B-cell lymphoma types could be divided into three broad groups for prognostic purposes: (i) low-risk group comprising follicular lymphoma and MALT; (ii) intermediate-risk group comprising diffuse large B-cell lymphoma and Burkitt lymphoma; and (iii) high-risk group comprising mantle cell lymphoma and lymphoblastic lymphoma. Among the T/NK-cell lymphomas, the commonest type was ATLL (n = 191; 48%), followed by peripheral T-cell lymphoma, unspecified (n = 83; 21%), angioimmunoblastic lymphadenopathy with dysproteinemia (AILD) (n = 38; 10%), anaplastic large cell lymphoma (ALCL) (n = 22; 6%). Less common types were lymphoblastic lymphoma (n = 17; 4%), nasal and nasal-type NK/T-cell lymphoma (n = 17; 4%), mycosis fungoides (MF) (n = 9; 2%) and other rare types. With respect to clinical prognosis, T/NK-cell lymphomas fell into three groups: (i) relative low-risk group comprising ALCL, AILD, MF and lymphoblastic lymphoma; (ii) relative intermediate-risk group comprising NK/T-cell lymphoma and unspecified lymphoma; and (iii) extremely high-risk group comprising ATLL. Among the lymphoblastic lymphomas, B-cell type and T-cell type lymphomas exhibited different clinical outcomes. We conclude that the histological, phenotypic and genotypic classification of the new WHO system should be beneficial for the clinical approach to these tumors.

Endemic Diseases↗

Mixed cryoglobulinemia in Greece. Primary disorders in 10 cases.

Mixed cryoglobulinemia (MC) is a systemic disorder whose pathogenesis is based on the presence of serum cryoglobulins. The purpose of this study was to evaluate on a prospective basis patients presenting with MC with regard to the clinical manifestations and the underlying disorders. We present ten patients with MC, who were diagnosed and followed up during a one year period in the Division of autoimmune rheumatic diseases (Clinical Department of Pathophysiology). MC was associated with hepatitis C virus (HCV) infection in two cases, with hepatitis B virus (HBV) infection in six, one patient had both HCV and evidence of HBV infection, while the remaining three patients fulfilled European classification criteria for diagnosis of Sjögren's syndrome (SS). In all ten cases, the presence of an underlying factor was identified, being either viral or autoimmune. It is concluded therefore that all patients presenting with MC should be completely evaluated for a hepatitis virus infection or an autoimmune or lymphoproliferative disorder. Furthermore, since the initiation of the process of MC is triggered by many factors, research should be directed towards the identification of the underlying common denominator.

Adult↗

Prognostic role of myocardial tumor necrosis factor-alpha and terminal complement complex expression in patients with dilated cardiomyopathy.

BACKGROUND: In patients with dilated cardiomyopathy (DCM), elevated plasma levels of tumor necrosis factor-alpha (TNF-alpha) are associated with poor prognosis. The terminal complement complex (C5b-9) stimulates myocardial TNF-alpha expression. AIMS: To investigate whether myocardial TNF-alpha and C5b-9 expression correlate with clinical outcome in DCM. METHODS AND RESULTS: 71 patients with DCM underwent myocardial biopsy. Biopsies were analyzed for TNF-alpha, C5b-9, markers of inflammation and for viral genome. Patients were divided into three groups according to biopsy results: group A: no TNF-alpha and no C5b-9; group B: TNF-alpha or C5b-9; and group C: TNF-alpha and C5b-9. NYHA classification, ECG and echocardiography were documented. Patients received conventional treatment of heart failure and, in a few cases, additional treatment with interferon beta(1b) (virus positive) or prednisolone (inflammatory DCM). There were 13 patients (18%) in group A, 19 patients (27%) in group B, and 39 patients (55%) in group C. All groups had a similar and significant improvement in NYHA classification and echocardiographic parameters. TNF-alpha and C5b-9 did not significantly correlate with the presence of viral genome or with markers of inflammation. CONCLUSION: TNF-alpha and C5b-9 are widely distributed in the myocardium of DCM patients. Neither of the antigens correlates with clinical outcome. Myocardial TNF-alpha may not be a useful prognostic marker in DCM.

Adult↗

Discovery of diverse anellovirus sequences in Thai human sequencing data.

UNLABELLED: Anelloviruses are part of the normal human viral flora. Although their diversity in humans has been investigated in many countries, and despite their initial detection in Thailand in 1999, knowledge of Thai anelloviruses remains very limited. This study analyzed 1,175 whole-genome sequencing data sets from Thai individuals to mine for potential anellovirus sequences. Our analyses detected anellovirus sequences in 149 data sets (12.68%), uncovering 434 partial anellovirus sequences and 77 complete genome sequences, characterized by the presence of terminal redundancy, complete orf1, and the conserved untranslated region upstream of the orf1 gene. Sequence analyses indicated that these viruses belong to seven genera, including Alphatorquevirus, Betatorquevirus, Gammatorquevirus, Hetorquevirus, Lamedtorquevirus, Samektorquevirus, and Yodtorquevirus. Notably, Hetorquevirus, Lamedtorquevirus, Samektorquevirus, and Yodtorquevirus had not previously been reported in Thailand. Phylogenetic analysis of ORF1 protein sequences showed that Thai anelloviruses form multiple phylogenetic clusters with non-Thai anelloviruses, indicating frequent cross-country transmission and multiple origins of the virus in Thailand. Furthermore, sequence similarity network analysis identified 33 potentially novel anellovirus species in our data set. Our findings greatly expand the knowledge of anellovirus diversity in Thailand and demonstrate the potential of human whole-genome sequencing data as a valuable resource for viral discovery. Lastly, we highlight and discuss some challenges with the use of the current pairwise sequence similarity-based classification scheme, in particular, how gaps can influence similarity calculation and potentially lead to inconsistencies with a phylogenetic-based classification scheme. IMPORTANCE: Anelloviruses are widespread in humans, yet their diversity remains poorly characterized in many regions, including Thailand. Here, we demonstrate that human sequencing data sets, originally generated without the intention for virome research, can be effectively mined for anellovirus sequences, including complete genomes. Our findings reveal a substantial number of previously unreported anelloviruses in Thailand, significantly expanding the known diversity of the virus. We also highlight potential limitations of the current anellovirus species classification scheme, which is based on pairwise orf1 sequence similarity analysis with a hard threshold cutoff at 69%. Our results reveal that the current scheme can sometimes yield taxonomic groupings that are inconsistent with phylogenetic relationships, particularly when significant alignment gaps are present. Overall, our results show that existing human sequencing data can be effectively repurposed for virus discovery research and suggest the need for more robust and phylogenetically informed classification frameworks as viral sequence databases continue to expand.

Humans↗

Phylogeny of viroids, viroidlike satellite RNAs, and the viroidlike domain of hepatitis delta virus RNA.

We report a phylogenetic study of viroids, some plant satellite RNAs, and the viroidlike domain of human hepatitis delta virus RNA. Our results support a monophyletic origin of these RNAs and are consistent with the hypothesis that they may be "living fossils" of a precellular RNA world. Moreover, the viroidlike domain of human hepatitis delta virus RNA appears closely related to the viroidlike satellite RNAs of plants, with which it shares some structural and functional properties. On the basis of our phylogenetic analysis, we propose a taxonomic classification of these RNAs.

Hepatitis Delta Virus↗

[Computerized scanning analyses of FITC-labelled microscopic slides (author's transl)].

FITC-labelled virus antigen was analysed in infected cells by means of scanning-fluorometry. According to the predetermined classification the values were computerized and printed out by a mosaic printer or by a coordinate-recorder as a profile graph or a perspective image. The total impression of the 3 dimensional print-out of the quantificated topographic distribution of antigen accumulations within the cells can be optimated by variation of the angle of view.

Animals↗

[A genetic study of the interaction of Piry virus with drosophila].

Piry virus mutants selected for altered growth properties in Drosophila melanogaster have previously been designated agD mutants. This paper presents a classification scheme for grouping some of these mutants and also presents the characteristics of some members of each group. Analysis, for each agD clone, of the mean incubation time at 20 degrees C relative to the mean incubation time at 28 degrees C (t20,t28), compared to the range of similar data for wild-type virus enabled us to define 4 classes of agD mutant: (1) mutants equally affected at both temperatures, (2) cold-sensitive mutants in drosophila (csD), (3) heat-sensitive mutants in drosophila (tsD) and (4) mutants whose mean incubation time could not be estimated at either 20 or 28 degrees C. All agD mutants are listed. The majority of them were also ts in chicken embryo cells (CEC), and some were classified into complementation groups. Some correlations were noted. For example, the agD mutants that were ts+ in CEC were frequently (7 out of 12) weakly cold-sensitive in drosophila. Those tsD mutants which were also ts in CEC, all belonged to complementation group I (L protein). True csD mutants, whose divergence of incubation time with wt regularly increased, and which were also ts in CEC, all belonged to group I except for one which belonged to group V (G protein). Three mutants fell into a distinct sub-class of csD mutants, characterized by a defect in the CO2 sensitivity symptom expression below a definite temperature. One of these which was further characterized was shown to be in complementation group V. Some mutants of the fourth class were examined for their fly-invading capacity. This was found to be more-or-less strongly affected. Among these mutants, independent of this phenomenon, mutations were assigned to L, N and G proteins, suggesting that different physiological defects are involved. A comparison was made of the phenotypes in drosophila of some of the agD mutants with other members of the vesiculovirus family. The analogy of sigma rhabdovirus with tsD mutants is also reported.

Animals↗

Serology of potyviruses: current problems and some solutions.

The serological relationships among members of the family Potyviridae are extremely complex and inconsistent. Variable cross-reactivity of polyclonal antisera, unexpected paired relationships between distinct viruses, and lack of cross-reactions between some strains are the major problems associated with the serology of potyviruses. Recent biochemical and immunochemical investigations of coat proteins have established the molecular basis for potyvirus serology and provided explanations for most of the problems with serology of potyviruses. Information from these studies has also formed the basis for the development of several novel approaches to the accurate detection and identification of potyviruses. However, even these novel approaches are not without drawbacks and some of them cannot be applied easily in plant virus laboratories, since they require prior sequence information and facilities for peptide synthesis. These findings suggest that serology is an imperfect criterion for the identification and classification of potyviruses.

Animals↗

Human immunodeficiency virus-related vasculitis. Clinical presentation of and therapeutic approach to eight cases.

Vasculitides occurring during the course of human immunodeficiency virus (HIV) infection are heterogeneous in their clinical presentation, time of occurrence, histological findings and etiological factors. Some of them can be directly attributed to HIV infection and their treatment might require new therapeutic approaches, such as plasma exchanges, specific antiviral agents and/or vasodilators. We report 8 cases of vasculitis associated with HIV. Five of them met the classification criteria of polyarteritis nodosa and had symptoms compatible with microscopic polyangiitis. Etiological agents were not identified. Although hepatitis B virus, hepatitis C virus (HCV) and other viruses or opportunistic agents were detected in some patients, HCV was suspected of being the etiological factor in only 1 of them. Focusing on viral and immunological features, the possible mechanisms of vasculitis development in HIV+ patients are discussed. Long-term follow-up indicates a clear benefit of regimens including antiviral agents, vasodilators and plasma exchanges. No deterioration of AIDS status was observed with this treatment and no relapse was recorded.

Adult↗

Expression of matrix metalloproteinase 9 in nasopharyngeal carcinoma and association with Epstein-Barr virus infection.

OBJECTIVE: To evaluate the expression of matrix metalloproteinase-9 (MMP9) in nasopharyngeal carcinoma and the association between MMP9 and Epstein-Barr virus infection. METHODS: The MMP9 expression was studied by immunohistochemical analysis; and Epstein-Barr virus encoded small nuclear mRNA-1 (EBER-1) produced by in situ hybridization were examined in 41 nasopharyngeal carcinoma sections, and the relation between them, and the associations of MMP9 with clinical features were statistically analyzed. RESULTS: Positive expression rate of MMP9 was 73.17%. The expression of MMP9 showed significant positive correlation with the expression of EBER-1 (gamma=0.483, P=0.001). There was significant association of MMP9 expression with lymph nodes metastasis and clinical stage (P<0.001), non-significant association with age, gender, pathological classification and T classification. CONCLUSIONS: The highly pronounced expression of MMP9 is associated with cervical lymph nodes metastasis. Epstein-Barr virus can enhance NPC metastasis by up-regulating the expression of MMP9.

Adult↗

Molecular epidemiology and immunology of hepatitis B virus infection - an update.

Hepatitis B virus (HBV) continues to be one of the most important viral pathogens in humans. This review provides an update on the molecular epidemiology and immunology of HBV infection. DNA sequencing has allowed replacement of the initial serotypic classification of HBV strains by a more systematic genotype system that currently consists of 7 members (genotypes A-G). More recently, sequence analysis of virus isolates from many individual patients has revealed the occurrence of certain mutational hot spots in the genome, some of which appear to correlate with the patient's immunological and/or disease status; however, cause and effect are not always easily discernible. This holds particularly for the issue of whether virus variants exist that have, per se, an increased pathogenic potential; due to the scarcity of appropriate experimental in vivo models, such hypotheses are difficult to prove. Similarly, because of the compact organization of the HBV genome, almost every single mutation may have pleiotropic phenotypic effects. Nonetheless, there is accumulating evidence that at least some frequently observed mutations are causally related to viral escape from selective pressures, such as the presence of antibodies against dominant B cell epitopes, or drugs that inhibit the viral reverse transcriptase; possibly, this is also true for the cellular immune response. Therefore, despite the availability of an effective prophylactic vaccine, further extensive efforts are required to monitor the emergence of vaccination- and therapy-resistant HBV variants and to prevent their spread in the general population.

Amino Acid Sequence↗

[The cryoglobulinemic syndrome--report from the workshop on classification and on the 10th conference of the Italian Society for the treatment of Cryoglobulinemia, Modena, 29 Sept., 2003].

The conference was preceded by a workshop of an European expert group on the n evaluation, testing, and workup of a new classification for cryoglobulinemic syndrome. Several studies on the potential role of infections, especially hepatitis C virus (HCV) and cytomegalovirus (CMV), in the pathogenesis of human autoimmune diseases were presented and discussed at the conference. A cross-reactivity between CMV proteins and different auto-antigens could play a role with respect to the initial endothelial damage in the pathogenesis of systemic sclerosis. A number of immune mechanisms may be involved in the induction of the cryoglobulinemic syndrome such as the formation of cross-reacting antibodies, chronic B-cell stimulation, an interaction between the HCV core protein and tumor suppressor genes p53 and/or proto-oncogens, and the t(14;18) translocation with bcl-2 activation and prolonged B-cell survival.

Cryoglobulinemia↗

Genetic markers applied in regression tree prediction models.

Classification and regression tree (CART) modelling was used to determine infectious hypodermal and haematopoietic necrosis virus (IHHNV) resistance and susceptibility in Penaeus stylirostris. In a previous study, eight random amplified polymorphic DNA (RAPD) markers and viral load values using real-time quantitative PCR were obtained and used as the training data set in order to create numerous regression tree models. Specifically, the genetic markers were used as categorical predictor variables and viral load values as the dependent response variable. To determine which model has the highest predictive accuracy for future samples, RAPD fingerprint data was generated from new Penaues stylirostris IHHNV resistant and susceptible individuals and used to test the regression models. The best performing tree was a four terminal node tree with three genetic markers as significant variables. Marker-assisted breeding practices may benefit from the creation of regression tree models that apply genetic markers as predictive factors. To our knowledge this is the first study to use RAPD markers as predictors within a CART prediction model to determine viral susceptibility.

Animals↗

Clinical features, diagnosis, and prognosis in rheumatoid arthritis.

The past year has witnessed a modest expansion in our understanding of the clinical, diagnostic, and prognostic features of rheumatoid arthritis. Almost every continent has reported prevalence, phenotype, and clinical features of rheumatoid arthritis subpopulations. Reviews of the natural history and therapy of cervical spine disease, Felty's disease, and lung involvement dominate the clinical literature. Rheumatoid arthritis-like syndromes have been reported to occur after immunotherapy with interferon alfa and interleukin-2. There have been case studies on human immunodeficiency virus, cachexia, pregnancy, "pseudosepsis," bone loss, and malignancy in rheumatoid arthritis. Diagnostic criteria and new classifications for functional and global impairment have been published, and new health impairment questionnaires have been evaluated. Novel isotopes and the role of magnetic resonance imaging in damaged joints were discussed. Rheumatoid factor was reaffirmed as a significant prognostic variable, and the roles of immunogenetic loci, sulfur oxidation, and serum matrix proteins were evaluated in early rheumatoid arthritis. Functional status was again verified as a strong prognostic marker.

Arthritis, Rheumatoid↗

Complete genome sequence of Montana Myotis leukoencephalitis virus, phylogenetic analysis and comparative study of the 3' untranslated region of flaviviruses with no known vector.

Montana Myotis leukoencephalitis virus (MMLV), a virus isolated from bats, causes an encephalitis in small rodents reminiscent of flavivirus encephalitis in humans. The complete MMLV genome is 10690 nucleotides long and encodes a putative polyprotein of 3374 amino acids. The virus contains the same conserved motifs in genes that are believed to be interesting antiviral targets (NTPase/helicase, serine protease and RNA-dependent RNA polymerase) as flaviviruses of clinical importance. Phylogenetic analysis of the entire coding region has confirmed the classification of MMLV in the clade of the flaviviruses with no known vector (NKV) and within this clade to the Rio Bravo branch (both viruses have the bat as their vertebrate host). We have provided for the first time a comparative analysis of the RNA folding of the 3' UTR of the NKV flaviviruses (Modoc, Rio Bravo and Apoi viruses, in addition to MMLV). Structural elements in the 3' UTR that are preserved among other flaviviruses have been revealed, as well as elements that distinguish the NKV from the mosquito- and tick-borne flaviviruses. In particular, the pentanucleotide sequence 5' CACAG 3', which is conserved in all mosquito- and tick-borne flaviviruses, is replaced by the sequence 5' C(C/U)(C/U)AG 3' in the loop of the 3' long stable hairpin structure of all four NKV flaviviruses. The availability of this latter sequence motif allows us to designate a virus as either an NKV or a vector-borne flavivirus.

3' Untranslated Regions↗

Experimental transmission and electron microscopic demonstration of the virus of haemorrhagic disease of rabbits in Czechoslovakia.

Intramuscular administration of the filtrate of organ suspensions, prepared from a dead rabbit, killed 62.9% of inoculated rabbits within 1 to 5 days, while 93.3% died after intranasal administration of the same inoculum. The virus survived freeze-drying and was resistant to treatment with 0.4% formaldehyde when incubated at 37 degrees C for 1 hour and 4 degrees C for the subsequent 12 hours, but lost its infectivity when the treatment was prolonged to 3 hours at 37 degrees C and 3 days at room temperature. Its infectivity was also inhibited by reconvalescent serum. The virus could not be detected after 3 passages in primary rabbit kidney cell cultures. Electron microscopy of negatively stained preparations demonstrated icosahedral virus particles with a diameter of 29 to 33 nm without an envelope. Accurate morphological classification has not yet been completed. Incubation with a reconvalescent serum, diluted 1:20 or 1:40, resulted in the formation of immune complexes, detectable by electron microscopy.

Animals↗

[Basic standards in handling patients with dengue fever, hemorrhagic dengue and dengue shock].

The Dengue epidemic in Venezuela has increase dramatically during the last years. There is a rise in the number of cases as well as in the severity of the disease. The fact that it circulates more than one serotype of the virus (1, 2 and 4), from the four described turn us into a hyperendemic region. The symptoms produce in the patient as a consequence of the infection with the Dengue virus, varies from a mild fever to the severe Dengue Shock. Here, the characteristics and classification of the different clinical manifestation are presented as well as the basic procedures in the management of the patient in every case.

Ambulatory Care↗