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[Behçet's disease and IgG lambda paraproteinemia].

The authors describe the clinical observation and therapeutic experience of the seven-year follow-up of a female patient with Behcet's disease according to the diagnostic classification criteria of the International Study Group (1990). The remarkable feature of the described observation is evidence of the herpes simplex virus type I in the oral cavity and in particular the five-year follow-up of stabilized paraproteinaemia IgG lambda of obscure impact.

Adult↗

[Clinical aspects of infection with feline leukemia virus in cats].

The leukemia-sarcoma complex constitutes the most common group of malignancies in the cat. Epizootiology of FeLV infections and pathogenesis, which can be divided into three stages, are described. Diagnosis can be made by immunofluorescent, ELISA and virus isolation techniques, as well as FOCMA-antibody tests. Symptomatology of FeLV related illnesses is presented. Feline lymphoma can be categorized into four anatomic types: thymic, alimentary and multicentric type and true leukemia. Forms, which do not fit this classification, are classified as miscellaneous. Treatment of these forms and prevention and control of FeLV infections are discussed.

Animals↗

Molecular epidemiology of Malaysian dengue 2 viruses isolated over twenty-five years (1968-1993).

The limited sequencing approach was used to study the molecular epidemiology of 24 Malaysian dengue 2 viruses which were isolated between 1968 and 1993. The sequences of a 240-nucleotide-long region across the envelope/non-structural 1 protein (E/NS1) gene junction of the isolates were determined and analysed. Alignment and comparison of the nucleotide and deduced amino acid sequences of the isolates revealed that nucleotide changes occurred mostly at the third position of a particular codon and were of the transition (A<-->G, C<-->U) type. Five nucleotide changes resulted in amino acid substitutions. Pairwise comparisons of the nucleotide sequences gave divergence values ranging from 0 to 9.2%. At the amino acid level, the divergence ranged between 0 and 3.8%. Based on the 6% divergence as the cut-off point for genotypic classification, the isolates were grouped into two genotypes, I and II. Comparison of the nucleotide sequences of the Malaysian dengue isolates with those of the dengue viruses of other regions of the world revealed that members of genotypes I and II were closely related to viruses from the Indian Ocean and Western Pacific regions, respectively.

Amino Acid Sequence↗

Relationships between structure and antiretroviral activity of thiosemicarbazone derivatives.

In an attempt to develop anti-AIDS drugs, the compound isatin beta-thiosemicarbazone has been subjected to systematic structural modifications. The resulting synthesized thiosemicarbazone derivatives (TSCDs) were examined for their ability to act as antiretrovirus agents in a model system--2M3/M cell system--consisting of B lymphocytes transformed by the v-abl oncogene and chronically infected with a retrovirus, the Moloney leukemia virus (M-MuLV). The efficacy of the synthesized TSCDs against retroviruses was determined by assaying the therapeutic index (TI) values of the compounds. The results enabled the classification of TSCD groups based on the relationship between chemical structure and antiretroviral activity. The compound N-allylisatin-beta':4'-diallylthiosemicarbazone showed the highest TI value and efficiently suppressed the chronic infection of M-MuLV in continuous long-term treatment.

B-Lymphocytes↗

Dermatologic findings and manifestations of acquired immunodeficiency syndrome (AIDS).

We present a review of the spectrum of human T-lymphotropic virus type III (HTLV-III) infection with particular emphasis on cutaneous manifestations in 217 patients. Correlations are made with immunodeficiency as measured by absolute T-helper cell number. A classification is presented of these dermatologic findings.

Acquired Immunodeficiency Syndrome↗

Rhesus lymphocryptovirus infection during the progression of SAIDS and SAIDS-associated lymphoma in the rhesus macaque.

SAIDS-associated lymphoma (SAL) represents a monoclonal expansion of B-cell origin in which simian immunodeficiency virus (SIV) infection is not detected. However, tumor cells are frequently infected with rhesus lymphocryptovirus (RhLCV), a rhesus homologue of Epstein-Barr virus (EBV). In previous studies, the incidence of RhLCV infection in SAL was determined to be 89% as measured by polymerase chain reaction (PCR) and/or in situ hybridization. The main objective of the present study was to ascertain whether the level of RhLCV infection in the SIV-infected macaque is influenced as a function of SAIDS progression, and/or whether increased levels of RhLCV infection may correlate with the development of SAL. To this end, RhLCV infection was evaluated in three independent groups: (1) in lymphomas from SIV-infected rhesus macaques, (2) in peripheral blood mononuclear cells (PBMC) from a cohort of 69 randomly selected healthy animals, and (3) in PBMC collected from 22 SIV-infected animals at various times during progression to SAIDS or SAL. The relative levels of RhLCV infection were evaluated by PCR/Southern blot analysis, visual comparison to a standard dilution series, and assignment of relative signal intensity to a uniform classification scheme. The data show that SIV-infected monkeys have a generally higher RhLCV load in PBMC than do healthy animals, but that the virus load varies widely among animals during disease progression. Increased RhLCV load does not occur uniformly during the progression of SAIDS, although evidence indicates an increased RhLCV viral load in the development of SAL.

Animals↗

Establishment of an IL-2-dependent cell line derived from 'nasal-type' NK/T-cell lymphoma of CD2+, sCD3-, CD3epsilon+, CD56+ phenotype and associated with the Epstein-Barr virus.

A novel interleukin-2 (IL-2)-dependent cell line, HANK1, was established from a patient with CD56+ NK/T-cell lymphoma arising in the retroperitoneum. Morphologically, HANK1 is a pleomorphic large cell line with irregular nuclei, which contains azurophilic granules in the cytoplasm. Immunophenotypic analysis showed that HANK1 expressed CD2, CD3epsilon, CD56, TIA-1, granzyme B, and HLA-DR, but no other T-lineage markers. These features were the same as seen in the original tumour, and are highly characteristic of nasal and 'nasal-type' NK/T-cell lymphoma as described in the proposed W.H.O. classification. Genotypically, this cell line also demonstrated the germline configuration of the T-cell receptor beta, gamma and the immunoglobulin heavy chain genes and clonal integration of the Epstein-Barr virus (EBV) together with antigen expression with a type II latency pattern (LMP-1+ and EBNA2-). Furthermore, Southern blot analysis using the EBV termini as probes confirmed its derivation from the original lymphoma, and revealed that it contained multiple copies of the EBV genome. Dose-dependent growth on IL-2 was observed in an in vitro study with a doubling time of 3 d at maximal stimulation. These data indicate that HANK1 seemed to preserve the biological characteristics of the original tumour and therefore may serve as a good model for the further analysis of unusual 'nasal-type' NK/T-cell lymphoma.

Blotting, Southern↗

Multiparameter analyses of spontaneous nonthymic lymphomas occurring in NFS/N mice congenic for ecotropic murine leukemia viruses.

Mouse strains congenic for ecotropic retrovirus genes have a much higher frequency of spontaneous lymphomas than the background NFS/N strain. In this study, most of these lymphomas have been identified as B-cell in origin by morphologic features, identification of immunoglobulin class, and cell-surface antigens. The classification suggested by Pattengale and Taylor proved to be applicable to the lymphomas studied. Most were of large follicular center cells and are considered typical of the type formerly designated as "reticulum cell sarcoma, type B." Many lymphomas contained a large proportion of nonneoplastic cells which partially obscured their neoplastic component. The role of ecotropic murine leukemia viruses as etiologic agents for B-cell lymphomas remains equivocal. However, because the only difference between the NFS/N and congenic mice is the expression of viruses in the latter, it appears that these viruses are somehow involved in induction of B-cell lymphomas.

Animals↗

[Large-cell anaplastic malignant CD30/Ki-1-positive T-type lymphoma, associated with STLV-1 virus (baboon malignant lymphoma model].

Large-cell anaplastic malignant lymphoma of T-type (T-LCAL) as an original form among human non-Hodgkin's malignant lymphomas in Updated Kiel Classification (1988) was defined. In human pathology T-LCAL presents a considerable diagnostic difficulties and is not associated with HTLV except some cutaneous forms. Comparative examination was carried out in 5 cases of baboon T-LCAL as a part of long-term investigation of the lymphoma outbreak in Sukhumi monkey stock. In tumor-bearing baboons routine morphological methods, immuno-morphological phenotyping of lymphoma cells with panel of MoAT and polyclonal antibodies to T- and B-lymphoid cell antigens and antigens of cell activation, including CD30 antigen, in cell suspension and on cryostate sections were used. STLV-provirus integration in DNA of lymphoma cells in PCR was determined. Diagnostically important morphological features of baboon and human T-LCAL include pronounced anaplasia and anisocytosis of CD30-positive large blast cells, tumour cell tendency to infiltrate sinuses and vascular walls. The presence of T-cell markers (CD2, CD3, CD4, CD8 in our cases) and antigens of cell activation (CD25, HLA-DR) were found. In DNA of baboon lymph node lymphomas (also in the cases without skin involvement) env- and tax-fragments of STLV-1 provirus were detected.

Animals↗

Classification and structure of echovirus 5'-UTR sequences.

Enteroviruses are classified into two genetic clusters on the basis of 5'-UTR and all echoviruses (ECV) are classified together with coxsackie B viruses (CBV), coxsackie A viruses (CAV) types 2-10, 12, 14 and 16, and enteroviruses (EV) 68, 69, 71 and 73. During the present study, 5'-UTR-derived sequences constituting the largest part of the Internal Ribosome Entry Site (IRES) of ECVs were studied with respect to their possible secondary structures, which were predicted following the phenomenon of "covariance", i.e. the existence of evolutionary pressure in favour of structural conservation in the light of nucleotide sequence variability. In this and previous studies, no correlation between overall 5'-UTR identity and the currently recognised Human Enterovirus species was found, implying that notwithstanding their divergent protein-encoding regions, these species are free to exchange 5'-UTRs by recombination. Secondary structure features which are known to be highly conserved amongst enteroviruses and specifically the GNRA tetraloop in secondary structure domain IV, involved in long-term tertiary interactions and loop B in secondary structure domain V with an as yet unknown function were also conserved in ECVs. In contrast, the C(NANCCA)G motif, which is considered to be important in virus transcription and translation, was not conserved in all ECVs and sequence patterns observed in other enterovirus groups and rhinoviruses were recorded.

5' Untranslated Regions↗

Contact inhibition of movement in the cultures of transformed cells.

Results of cell-cell collisions were studied with the aid of time-lapse microcinematography in primary cultures of normal mouse-embryo fibroblast-like cells and in cultures of transformed mouse cells of two types: (a) primary fibroblast-like cells transformed by Moloney mouse sarcoma virus; (b) neoplastic fibroblasts of the CIM strain. Collisions of normal fibroblast-like cells and CIM cells in mixed cultures were also analyzed. Classification of the results of collisions was based on observation of the movements of the active cell edge during the first hour after the moment when this edge had contacted another cell. Three types of collision results were detected: halt of the active edge, overlapping, and underlapping. The relative number of overlappings was not higher and that of halts not lower in the cultures of transformed cells as compared with those of normal cells. Analysis of the collisions of normal fibroblasts with transformed cells gave similar results. Thus, the altered morphology of the cultures of these transformed cells cannot be explained by loss of contact inhibition of movement leading to increased ability of cells to move over the surfaces of other cells after collision.

Animals↗

Antigenic and genetic characterization of rabies viruses isolated from domestic and wild animals of Brazil identifies the hoary fox as a rabies reservoir.

Fifty Brazilian rabies viruses, collected from many different animal species and several regions of the country, were characterized by partial sequencing of the central, variable region of the P gene, a locus useful for sensitive molecular epidemiological studies. Phylogenetic analysis of the sequences, which included comparison with other rabies strains recovered from throughout the Americas, identified three main groups of Brazilian viruses, arbitrarily designated BRL-1 to BRL-3. BRL-1 was found in terrestrial carnivores and clusters with other American strains of the cosmopolitan lineage. BRL-2 comprised two distinct isolates, recovered from two species of non-haematophagous bats, that had evolutionary links to insectivorous-bat-derived strains of North America. BRL-3 consisted of isolates from vampire bats and from livestock species probably infected via contact with vampire bats. The terrestrial group was further subdivided into three subtypes: BRL-1a was associated exclusively with dogs and cats, while BRL-1b and BRL-1c were found exclusively in hoary foxes. These observations strongly support the role of the Brazilian hoary fox as a rabies reservoir. Screening of representative Brazilian rabies viruses against a collection of anti-rabies monoclonal antibodies (mAbs) identified a small panel of mAbs that could be used to discriminate between all Brazilian subgroups as defined by genetic classification in this study.

Animals↗

Correlations of portal hypertensive gastropathy of hepatitis B cirrhosis with other factors.

OBJECTIVE: To study the clinical relations of portal hypertensive gastropathy (PHG) of hepatitis B cirrhosis to other factors. METHODS: Three groups of subjects were studied prospectively at our hospital from March 2000 to March 2001: 159 hepatitis B cirrhotic patients with portal hypertension, 114 hepatitis B cirrhotic patients without portal hypertension, and 97 control subjects. Free portal vein pressure (FPP) was measured during surgery. Liver function was assessed by Pugh's modification of Child's criteria. The area of liver collagen fibrin was studied using color image analysis system. Esophageal varices were identified by Dagradi grading. Gastric varices were identified according to Northern Italian Endoscopic Council (NIEC) grading. Hypersplenism was assessed with the reduction of WBC, HGB and PLT. Hepatitis B virus in the gastric mucosa was detected by immunizing histochemistry. Helicobacter pylori (H. pylori) organisms were identified by rapid urease testing and/or examination of the stained biopsy specimens (haematoxylin and eosin). To analyze the correlation between these endoscopic signs at the gastric level and other factors. RESULTS: The differences of FPP among the three groups (patients with grade I, II, and III gastropathy) were not significant. There was no correlation between Child-Pugh classification grading and the severity of gastropathy (P=0.153). The differences of the area of liver collagen fibrin among the three grade gastropathy were not statistically significant (P=0.801). There was a significant difference in the prevalence of severe PHG among grade I, II, III, IV and V esophageal varices (P<0.001). PHG was present in a similar percentage of patients with gastric varices compared with those without gastric varices (P=0.209). There was a significant difference in the severity between PHG and hypersplenism (P=0.003). Seven patients with PHG had no microscopic evidence of hepatitis B virus infection in the gastric wall. There was no correlation between Child-Pugh classification grading and infection of H. pylori (P=0.7491). CONCLUSIONS: The most important element causing PHG is the increased portal pressure as a prerequisite. In addition, other factors may contribute to the development of PHG. PHG often occurs in patients with the presence of esophageal varices. There is a marked correlation between the severity of PHG and hypersplenism. Hepatitis B virus and H. pylori infection are unlikely to be involved in the pathogenesis of PHG. The development of PHG is less influenced either by the severity of liver disease (Child-Pugh grade) and cirrhosis or by the presence or non presence of gastric varices.

Adult↗

Sequence analysis of the 3'-terminal half of RNA 1 of wheat spindle streak mosaic virus.

cDNA complementary to the 3'-terminal half of RNA 1 of wheat spindle streak mosaic virus (WSSMV) from Southern France has been cloned and sequenced. One large open reading frame (ORF) of 4410 nucleotides and a nontranslated region (NTR) of 213 nucleotides at the 3'-end excluding the poly(A)-tail were found. Because of the amino acid sequence homology to the polyprotein of barley yellow mosaic virus (BaYMV) RNA 1, the encoded polyprotein of the sequenced region of WSSMV is supposed to comprise the C-terminal part of the putative cytoplasmic inclusion (CI) protein, the nuclear inclusion a (NIa) proteinase, the (NIb) RNA-polymerase and the capsid protein. The first 19 N-terminal amino acids of the capsid protein were determined by direct sequencing of proteins of purified WSSMV particles and confirmed this hypothesis. The deduced capsid protein has 294 amino acids and shows 74% identity with the BaYMV capsid protein sequence. This high sequence homology with BaYMV, in addition to the significant identities with barley mild mosaic virus (BaMMV, 35%) and its marginal homology to capsid protein sequences of aphid and mite-borne potyviruses (22-24%), supports the classification of WSSMV as a distinct member of the genus Baymovirus, family Potyviridae.

Amino Acid Sequence↗

[Pulmonary arterial hypertension].

INTRODUCTION: Pulmonary arterial hypertension (PAH) is a rare condition characterised by progressively elevated pulmonary arterial resistance leading to right heart failure. STATE OF THE ART: A recent classification distinguishes idiopathic PAH, familial PAH and PAH secondary to other conditions (connective tissue disease, congenital heart disease, portal hypertension, human immunodeficiency virus infection or appetite suppressant exposure). Echocardiography is the initial investigation of choice for non-invasive detection of PAH but measurement of pulmonary pressures and cardiac output during right-heart catheterization are necessary to confirm the diagnosis of PAH. Conventional treatment includes non-specific drugs (warfarin, diuretics, oxygen). Intravenous epoprostenol is the first-line treatment for the most severely affected patients. In less severe cases, the first-line treatment may include bosentan or a prostacyclin analogue. PERSPECTIVES AND CONCLUSIONS: Recent advances in the management of PAH have markedly improved prognosis. The avai-lability of novel specific drugs including type 5 phosphodiesterase inhibitors offers novel therapeutic perspectives but their exact role in the treatment of PAH is still uncertain. The evolution of therapy from vasodilators to antiproliferative agents reflects the advancement in our understanding of the mechanisms mediating pulmonary arterial hypertension.

Antihypertensive Agents↗