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[Adult living donor liver transplantation. Analysis of the first 30 cases].

INTRODUCTION: In the last 2-3 years, adult living donor liver transplantation (ALDLT) has been developed on an international scale, multiplying the number of procedures performed. Despite this, analysis of the results is still incomplete. The aim of the present study was to perform a descriptive analysis of the results after the first 3 years of the initiation of the program. MATERIAL AND METHODS: During this period, 30 ALDLT were performed. In all procedures, right lobe grafts were used. The mean age of donors and recipients was 31.8 and 52.7 years, respectively. The main indication for liver transplantation was liver cirrhosis due to hepatitis C virus (70%) and 38% of recipients were stage C in the Child-Pugh classification. A total of 46.7% of recipients had hepatocellular carcinoma. RESULTS: Donors: The mean volume of the remnant liver was 632 cc (40.5% of the previous hepatic mass). Ten donors (33%) presented complications. The most frequent complication was biliary fistula (20%) and three patients required reintervention. The mean length of hospital stay among donors was 11.7 days. Recipients: The mean weight of the graft was 775 g, with a mean difference between graft weight and that of the recipient of 1.11. Fifteen recipients (50%) presented biliary leaks and nine of these (30%) required reintervention. There were no graft losses for technical reasons. Four patients died. With a median follow-up of 14 months, actuarial survival at 18 months was 92.9%. CONCLUSION: ALDLT is an effective method for reducing the number of patients on the waiting list. The probability of survival is similar to that of cadaveric transplantation. Biliary complications in the recipient constitute a problem, the long-term repercussions of which remain to be resolved.

Adolescent↗

[Corneal endotheliitis. Definition and clinical classification].

Corneal endotheliitis in the narrower sense is the term applied to immune reactions directed against the endothelial cells themselves. Virus antigens, histocompatibility antigens and autoantigens in the cell membrane represent the target for immune attack. The most significant clinical sign of endotheliitis is a strict correlation between the area of endothelial damage and the area of the (immune) precipitates.

Adult↗

Observer variation, dysplasia grading, and HPV typing: a review.

Squamous dysplasia of the cervix is a morphologic continuum that is divided into a number of categories. When the severity of a morphologic abnormality is assessed, whether in a biopsy sample or in an exfoliative smear, there can be significant observer variation. The statistical quantification of this variation, with particular reference to the kappa statistic and the influence of the number of categories utilized on the kappa statistic, is discussed. The contribution of information theory to the understanding of the reasons for observer variation is explored. The use of a binary (Bethesda) system of classification of squamous dysplasia and its validation by comparing consensus diagnoses with human papilloma virus type both in biopsy samples and in smears is reviewed.

Bacteriophage Typing↗

Skin diseases in children with HIV infection and their association with degree of immunosuppression.

Since the recognition of the acquired immunodeficiency syndrome (AIDS) in 1981, several dermatologic manifestations have been associated with the syndrome, including candidiasis, dermatophyte infection, molluscum contagiosum, herpes simplex and zoster, bacterial infection, and malignancy. Skin diseases have been observed in both the adult and the pediatric human immunodeficiency virus (HIV) infection in an academic hospital setting in relationship to the current CDC classification of pediatric HIV infection. The severity of dermatologic manifestations is correlated with the immune status of the patients. The latter was determined by T4 helper cell numbers and lymphoproliferative responses to mitogens and recall antigens. More severe T helper cell depletion was associated with a wider spectrum and increased severity of dermatologic manifestations.

Acquired Immunodeficiency Syndrome↗

Morphologic and immunophenotypic characteristics of malignant lymphomas in SIV-infected rhesus macaques.

Eight cases of extranodal non-Hodgkin's lymphoma in simian immunodeficiency virus (SIV)-infected rhesus macaques, aged 4-9 years, were phenotypically and immunologically characterized, using the updated Kiel classification, in order to determine both the differences and the similarities between these types of lymphoma in immunodeficient rhesus macaques (Macaca mulatta) and man. The high-grade malignant tumors were of B-cell origin, with a predilection for extranodal growth in viscera and periorbital tissues. Immunophenotypical characterization showed that the monkey lymphomas were similar in many aspects to human immunodeficiency virus-associated lymphomas. The number of Ki67 positive cells varied from case to case and ranged from 50 to 90%. A serological screening for the simian equivalent of the Epstein-Barr virus (sEBV) by immunofluorescence assay revealed a prevalence of 92% of the sEBV antibodies in our cohort. The presence of Ebstein-Barr virus nuclear antigen (EBNA-2) could be demonstrated by immunohistochemistry in four out of eight cases. In situ hybridization revealed the presence of small EBV-encoded RNAs (EBER-1, EBER-2) in six of the eight cases. Further studies should define the precise role of herpesvirus infection for lymphomagenesis in SIV-induced immunodeficiency.

Animals↗

Hodgkin's lymphoma: the pathologist's viewpoint.

Despite its well known histological and clinical features, Hodgkin's lymphoma (HL) has recently been the object of intense research activity, leading to a better understanding of its phenotype, molecular characteristics, histogenesis, and possible mechanisms of lymphomagenesis. There is complete consensus on the B cell derivation of the tumour in most cases, and on the relevance of Epstein-Barr virus infection and defective cytokinesis in at least a proportion of patients. The REAL/WHO classification recognises a basic distinction between lymphocyte predominance HL (LP-HL) and classic HL (CHL), reflecting the differences in clinical presentation and behaviour, morphology, phenotype, and molecular features. CHL has been classified into four subtypes: lymphocyte rich, nodular sclerosing, with mixed cellularity, and lymphocyte depleted. The borders between CHL and anaplastic large cell lymphoma have become sharper, whereas those between LP-HL and T cell rich B cell lymphoma remain ill defined. Treatments adjusted to the pathobiological characteristics of the tumour in at risk patients have been proposed and are on the way to being applied.

Diagnosis, Differential↗

HPV typing and CGH analysis for the differentiation of primary and metastatic squamous cell carcinomas of the aerodigestive tract.

Human papilloma virus (HPV) typing and Comparative Genomic Hybridisation (CGH) analysis can be used in the classification of multiple tumours of the aerodigestive tract for the differentiation between secondary malignancy versus metastasis. We present 3 exemplary cases of patients with multiple squamous cell carcinomas, localised within the head and neck region, cervical lymph node and the lung. In two patients, HPV typing identified HPV type 16 in the tonsillar carcinomas and the corresponding cervical lymph node and lung carcinoma indicating that the latter were metastatic spreads. In case 1, CGH confirmed the clonal relationship. Case two showed a peculiar syncytial growth pattern with lymphocytic infiltration which may constitute a potential morphological marker for HPV infection. In case three, a vallecular carcinoma was HPV negative while a lung cancer was positive for HPV type 6 indicating two independent primary tumours. Our case triplet illustrates the variability of HPV infection in squamous cell cancer of the aerodigestive tract and power as well as limitations of morphology, HPV typing and tumour genetics in the classification of multiple tumours.

Carcinoma, Squamous Cell↗

Identification and classification of human cytomegalovirus capsids in textured electron micrographs using deformed template matching.

BACKGROUND: Characterization of the structural morphology of virus particles in electron micrographs is a complex task, but desirable in connection with investigation of the maturation process and detection of changes in viral particle morphology in response to the effect of a mutation or antiviral drugs being applied. Therefore, we have here developed a procedure for describing and classifying virus particle forms in electron micrographs, based on determination of the invariant characteristics of the projection of a given virus structure. The template for the virus particle is created on the basis of information obtained from a small training set of electron micrographs and is then employed to classify and quantify similar structures of interest in an unlimited number of electron micrographs by a process of correlation. RESULTS: Practical application of the method is demonstrated by the ability to locate three diverse classes of virus particles in transmission electron micrographs of fibroblasts infected with human cytomegalovirus. These results show that fast screening of the total number of viral structures at different stages of maturation in a large set of electron micrographs, a task that is otherwise both time-consuming and tedious for the expert, can be accomplished rapidly and reliably with our automated procedure. Using linear deformation analysis, this novel algorithm described here can handle capsid variations such as ellipticity and furthermore allows evaluation of properties such as the size and orientation of a virus particle. CONCLUSION: Our methodological procedure represents a promising objective tool for comparative studies of the intracellular assembly processes of virus particles using electron microscopy in combination with our digitized image analysis tool. An automated method for sorting and classifying virus particles at different stages of maturation will enable us to quantify virus production in all stages of the virus maturation process, not only count the number of infectious particles released from un infected cell.

Algorithms↗

[Classification and index of necrotizing vasculitis].

The diagnosis of necrotizing vasculitis rests on histology which shows parietal fibrinoid necrosis, vascular and perivascular infiltrates and intraluminal thrombosis in varying degrees of association. However, histopathological classifications of necrotizing vasculitis according to the size of the diseased vessels or the appearance of vascular infiltrates are not satisfactory, since microvasculitis may successively to simultaneously involve vessels of different calibers and result (generally in succession) in leukoclastic or lymphocytic vasculitis. For this reason we give preference to an aetiological classification which includes five major entities, some of which were described over a century ago (periarteritis nodosa, Churg-Strauss syndrome, Wegener's disease, rheumatoid purpura and Mac Duffie syndrome); drug-induced vasculitis, infective vasculitis, vasculitis associated with blood diseases; vasculitis of connective tissue diseases; vasculitis that may accompany some system diseases (e.g. Kawasaki disease and Cogan's syndrome); and vasculitis that may complicate cryoglobulinaemia or congenital deficiencies in complement fraction or in alpha-1 antitrypsin. It can be seen that this is not the ideal classification, since the same causative agent may be found in several chapters (e.g. HB virus in periarteritis nodosa, infective vasculitis and cryoglobulinaemia). We describe in detail only those types of vasculitis which are not treated in other in this issue of the Revue du Praticien, notably Wegener's disease, Mac Duffie syndrome and Kawasaki disease.

Humans↗

[Serotyping of hemorrhagic fever with renal syndrome in Hubei province].

Ninety-two serum specimens, positive for antibodies against hemorrhagic fever with renal syndrome (HFRS) virus in initial screening with immunofluorescence assay technic (IFAT), were serotyped with micro cell pathogenic effects neutralization test based on preliminary epidemiological classification of epidemic foci of HFRS throughout the province to find out serological evidence of HFRS typing in Hubei Province. It was found that 48 of the specimens were belonged to Type I (HTN) accounting for 52.18 percent, 29 Type II (SEO) for 31.52 percent, and 15 undefined for 16.30 percent. Hubei Province was classified serologically as a mixed prevalent area with Type I as its major component, but all serotypes in different sub-areas have their own features and those in the old epidemic foci were more complex. It indicated that it was better to use a bivalent HFRS virus vaccine, or a single-valent vaccine consistent with local serotype. Serotyping of local HFRS conformed basically to that of epidemiological classification. Local HFRS should be serotyped periodically due to continuous changes in types of foci. Attention to reactions of vaccine immunization should be paid during observation of the effectiveness of the vaccine.

China↗

A comprehensive panel of near-full-length clones and reference sequences for non-subtype B isolates of human immunodeficiency virus type 1.

Non-subtype B viruses cause the vast majority of new human immunodeficiency virus type 1 (HIV-1) infections worldwide and are thus the major focus of international vaccine efforts. Although their geographic dissemination is carefully monitored, their immunogenic and biological properties remain largely unknown, in part because well-characterized virological reference reagents are lacking. In particular, full-length clones and sequences are rare, since subtype classification is frequently based on small PCR-derived viral fragments. There are only five proviral clones available for viruses other than subtype B, and these represent only 3 of the 10 proposed (group M) sequence subtypes. This lack of reference sequences also confounds the identification and analysis of mosaic (recombinant) genomes, which appear to be arising with increasing frequency in areas where multiple sequence subtypes cocirculate. To generate a more representative panel of non-subtype B reference reagents, we have cloned (by long PCR or lambda phage techniques) and sequenced 10 near-full-length HIV-1 genomes (lacking less than 80 bp of long terminal repeat sequences) from primary isolates collected at major epicenters of the global AIDS pandemic. Detailed phylogenetic analyses identified six that represented nonrecombinant members of HIV-1 subtypes A (92UG037.1), C (92BR025. 8), D (84ZR085.1 and 94UG114.1), F (93BR020.1), and H (90CF056.1), the last two comprising the first full-length examples of these subtypes. Four others were found to be complex mosaics of subtypes A and C (92RW009.6), A and G (92NG083.2 and 92NG003.1), and B and F (93BR029.4), again emphasizing the impact of intersubtype recombination on global HIV-1 diversification. Although a number of clones had frameshift mutations or translational stop codons in major open reading frames, all the genomes contained a complete set of genes and three had intact genomic organizations without inactivating mutations. Reconstruction of one of these (94UG114.1) yielded replication-competent virus that grew to high titers in normal donor peripheral blood mononuclear cell cultures. This panel of non-subtype B reference genomes should prove valuable for structure-function studies of genetically diverse viral gene products, the generation of subtype-specific immunological reagents, and the production of DNA- and protein-based subunit vaccines directed against a broader spectrum of viruses.

Adolescent↗

Classical swine fever virus diversity and evolution.

By analysing the nucleotide sequence data generated from both the E2 (gp55) and the NS5B genes of classical swine fever virus (CSFV), in addition to previously published data from the 5'NCR, we were able to divide 115 CSFV isolates into two major groups, five subgroups and two disparate isolates. Further discrimination was possible by analysis of sequence data from the E2 region. The three sequencing based methods were compared to monoclonal antibody (MAb) typing and to limited restriction enzyme (RE) mapping. Although both MAb and RE methods confirmed the previous classification the resolution was inferior. We estimated an approximate evolution rate for CSFV from an analysis of the virus variation observed in a single geographical area over a 6 year period. Applying this proposed rate to each of our deduced CSFV subgroups enabled us to calculate the approximate dates of divergence for each subgroup.

Animals↗

Metagenome-Based Characterization of the Gut Virome Signatures in Patients With Gout.

The gut microbiome has been implicated in the development of autoimmune diseases, including gout. However, the role of the gut virome in gout pathogenesis remains underexplored. We employed a reference-dependent virome approach to analyze fecal metagenomic data from 102 gout patients (77 in the discovery cohort and 25 in the validation cohort) and 86 healthy controls (HCs) (63 and 23 in each cohort). A subset of gout patients in the discovery cohort provided longitudinal samples at Weeks 2, 4, and 24. Our analysis revealed significant alterations in the gut virome of gout patients, including reduced viral richness and shifts in viral family composition. Notably, Siphoviridae, Myoviridae, and Podoviridae were depleted, while Quimbyviridae, Retroviridae, and Schitoviridae were enriched in gout patients. We identified 359 viral operational taxonomic units (vOTUs) associated with gout. Enriched vOTUs in gout patients predominantly consisted of Fusobacteriaceae, Bacteroidaceae, and Selenomonadaceae phages, while control-enriched vOTUs included Ruminococcaceae, Oscillospiraceae, and Enterobacteriaceae phages. Longitudinal analysis revealed that a substantial proportion of these virome signatures remained stable over 6 months. Functional profiling highlighted the enrichment of viral auxiliary metabolic genes, suggesting potential metabolic interactions between viruses and host bacteria. Notably, gut virome signatures effectively discriminated gout patients from HCs, with high classification performance in the validation cohort. This study provides the first comprehensive characterization of the gut virome in gout, revealing its potential role in disease pathogenesis and highlighting virome-based signatures as promising biomarkers for gout diagnosis and future therapeutic strategies.

Humans↗

Sequence variation and evolution of Cryphonectria hypovirus 1 (CHV-1) in Europe.

Cryphonectria hypovirus 1 (CHV-1) acts as a naturally occurring biological control agent for chestnut blight, a destructive fungal disease of chestnut trees, which has been introduced into Europe in the 1930s. We have determined partial nucleotide and deduced amino acid sequences of the ORF A of 47 CHV-1 isolates collected in Europe over a period of 28 years. Phylogenetic analysis revealed the presence of four groups or single viruses, which showed sequence divergences ranging from 11 to 19%. These results confirm the previous subtype classification based on RFLP markers, with the exception of the two CHV-1 subtypes E and D, which appear to be related closer than anticipated previously. Dates of divergences between CHV-1 subtypes, calculated from nucleotide substitution rates, indicate that the CHV-1 subtypes diverged several hundreds years ago. Our results suggest that the genetic variation among CHV-1 subtypes did not evolve in Europe and support the hypothesis of multiple introductions of CHV-1 into Europe.

Ascomycota↗

Identification and genome characterization of Heliothis armigera cypovirus types 5 and 14 and Heliothis assulta cypovirus type 14.

Genomic characterization of Heliothis armigera cypovirus (HaCPV) isolated from China showed that insects were co-infected with several cypoviruses (CPVs). One of the CPVs (HaCPV-5) could be separated from the others by changing the rearing conditions of the Heliothis armigera larvae. This finding was further confirmed by nucleotide sequencing analysis. Genomic sequences of segments S10-S7 from HaCPV-14, S10 and S7 from HaCPV-5, and S10 from Heliothis assulta CPV-14 were compared. Results from database searches showed that the nucleotide sequences and deduced amino acid sequences of the newly identified CPVs had high levels of identity with those of reported CPVs of the same type, but not with CPVs of different types. Putative amino acid sequences of HaCPV-5 S7 were similar to that of the protein from Rice ragged stunt virus (genus Oryzavirus, family Reoviridae), suggesting that CPVs and oryzaviruses are related more closely than other genera of the family Reoviridae. Conserved motifs were also identified at the ends of each RNA segment of the same virus type: type 14, 5'-AGAAUUU...CAGCU-3'; and type 5, 5'-AGUU...UUGC-3'. Our results are consistent with classification of CPV types based on the electrophoretic patterns of CPV double-stranded RNA.

Amino Acid Sequence↗