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Determination of the taxonomic position and characterization of yam mosaic virus isolates based on sequence data of the 5'-terminal part of the coat protein cistron.

The sequences of the N-terminal part of the coat protein cistron from six isolates of yam mosaic virus (YMV-TOG, YMV-COT, YMV-12, YMV-CAR, YMV-BU1 and YMV-BU2) were determined. The analysis of the deduced amino acid sequences revealed the presence of consensus motifs characteristic of the potyvirus genus supporting the classification of YMV as a potyvirus member. The alignment of the N-terminal part of the coat protein of YMV-TOG, YMV-COT, YMV-12 and YMV-CAR showed that they were identical in size (152 aa) while YMV-BU1 and YMV-BU2 were shorter (140 aa) due to a deletion of 12 aa. These amino acid sequences exhibit an overall sequence identity ranging from 70.4% to 97.4% while the identity level with the other potyviruses sequenced in the considered region is below 50%, confirming that YMV is a distinct member of the potyvirus genus. The detailed analysis of the amino acid sequence alignment and of the identity levels observed between the N-terminal part of the coat protein of the six YMV isolates lead us to suggest that they have to be considered as distantly related strains of YMV rather than closely related but distinct viruses.

Amino Acid Sequence↗

Genomic characterization of hepatitis C virus isolates from Argentina.

Thirty-three Argentinian patients infected with hepatitis C virus (HCV) were studied for viral genotyping. The patients included 10 hemophiliac and 4 polytransfused children and 19 adults: 3 polytransfused, 7 dialyzed and 9 sporadic cases. Core-based genotyping permitted the classification of 31 samples. Genotypes II, I and V were the most frequent: 21 (63.6%), 16 (48.4%) and 10 (30.3%) of the 33 patients, respectively. Only one polytransfused patient carried genotype IV. Genotype II was detected in 7 out of 9 sporadic cases. Thirteen patients (39.3%) were coinfected with two genotypes, and 2 others were coinfected with three genotypes. The remaining 2 samples which could not be typed were characterized following the restriction fragment length polymorphism (RFLP) method, and were classified as type 1. One of these had two consecutive transitional mutations in the 5' untranslated region (5' UTR).

Adult↗

Undetected hepatocellular carcinoma: clinical features and outcome after liver transplantation.

The aim of the study was to define the clinical characteristics and outcome of patients found to have an undetected hepatocellular carcinoma (HCC) at liver transplantation. Patients who underwent liver transplantation and were found to have a hepatoma with a prior workup showing normal alpha-fetoprotein levels and no corresponding lesion on radiological evaluation were defined as having an undetected HCC. Detailed information was collected, and the last abdominal computed tomographic (CT) scan before transplantation was performed was retrospectively reviewed. Thirty-nine patients had a tumor that met the criteria for an undetected hepatoma. The most common causes for pretransplantation liver disease were hepatitis C virus (HCV) (49%) and alcohol use (28%). Tumor size was 2 cm or less in 85% of the patients, vascular invasion was detected in 31% of the patients, and tumor, node, metastasis (TNM) classification was stage I or II in 77% of the patients. Review of the last CT scan before transplantation showed that the lesion was evident in retrospect in only 15% of the patients. Thirty-two patients (82%) remained alive at the time of the study with a mean follow-up of 30 months. Metastatic HCC was detected in 1 patient 7 months after transplantation. There were no other tumor recurrences. Survival analysis showed no significant differences when tumor size, stage, presence of vascular invasion, or causes of pretransplantation liver disease were compared. Undetected HCCs represent a significant percentage of total hepatomas in patients undergoing liver transplantation. Most patients have small, early-stage tumors, but tumors greater than 2 cm or of advanced stage are also frequently found in this population. Overall and tumor-free survival appear to be favorable.

Adult↗

Natural history of HIV-infection in hemophiliacs: clinical, immunological, and virological findings.

At our institution 686 hemophiliacs are being treated. Of them 402 (59%) are anti-HIV-seropositive. The general use of heat-treated clotting factor products was begun in July 1983, and from May 1984 all patients exclusively used heat-treated clotting factors. Thus, one can assume that infection occurred no later than early 1984 in our patients. Since December 1985 HIV-positive hemophiliacs have regularly been clinically and immunologically examined. Most of the 306 patients who could be investigated were clinically symptom-free at the time of their first visit. However, 45 patients have developed AIDS from 1982 through August 1988. The mean survival time of hemophiliacs with AIDS is less than 6 months. In 36% of those 274 patients who have been followed for a mean period of 14 months the clinical stage of the disease worsened by at least one stage according to the classification system proposed by the Centers for Disease Control. We did not find a correlation between clotting-factor consumption during the years 1984-1986 and the actual clinical stage of the patients. Virus isolation from peripheral blood lymphocytes (PBIs) answered the question whether anti-HIV seropositive hemophiliacs are not only immunized but really infected in many more cases than those revealed by detection of p24 antigen or decline of p24 antibody. Positive viral culture correlated strongly with a drop in CD4+ lymphocytes under the level of 400/microliters. However, HIV could not be cultured regularly in advanced cases, suggesting that virus replication in PBLs is not necessarily the cause of depletion of T-helper cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Oncogenes.

Oncogenes were first identified in neoplastic tissues and were thought to be disseminated by retroviruses. They were shown to cause neoplastic transformation of cells in vitro and were therefore regarded as "the genes that cause cancer." They occur in all eukaryotes including humans. More than 30 oncogenes have been identified, and 28 have already been mapped to the human karyotype. When the protein products of the oncogenes were investigated, they were found to be very similar to known substances that are normally involved in the control of cell division--growth factors, plasma-membrane receptors, modulators of the transduction of exogenous signals through the plasma membrane, and nuclear DNA-binding substances. These discoveries changed the original concept of oncogenes. They are now regarded as playing vital roles in the normal control of mitosis, and they should properly be called mitogenes rather than "oncogenes." Like all other genes, if a mitogene is mutated, rearranged, translocated, or otherwise deranged, its effects will change; it may then become an oncogene that will promote disorderly cell division and thus contribute to the pathogenesis of cancer. In addition to providing new insights into the normal control of mitosis and its neoplastic transformation, the discovery of the mitogenes has suggested new approaches to the early diagnosis of cancer, to a more rational classification of neoplasms based on pathogenesis rather than morphology, and, perhaps, to more rational forms of therapy.

Animals↗

Avian pneumoviruses and emergence of a new type in the United States of America.

Avian pneumovirus (APV) primarily causes an upper respiratory disease recognized as turkey rhinotracheitis (TRT) or swollen head syndrome (SHS) in chickens. The virus was first isolated in South Africa during the early 1970s and has subsequently been reported in Europe, Asia and South America. In February 1997, a serologically distinct APV isolate was officially reported in the USA following an outbreak of TRT during the previous year. This was the first report of these virus types in the USA; they were previously considered exotic to the USA and Canada. The predicted matrix (M) proteins of European APV type A and B isolates share 89% identity in their amino acid sequence. However, the predicted M protein of APV/CO is only 78% similar to the APV type A and 77% similar to the APV type B protein sequence. The predicted amino acid sequence of the US APV isolate's fusion (F) protein has 72% sequence identity to the F protein of APV type A and 71% sequence identity to the F protein of type B. This compares with the 83% sequence identity between the predicted amino acid sequences of the F proteins of APV types A and B. The lack of sequence heterogeneity among the US APV isolates over 2 years suggests that these viruses have maintained a relatively stable population since the first outbreak of TRT. Phylogenetic analysis of the M and F proteins, together with the serological uniqueness of the US APV isolates, supports their classification as a new APV, designated type C.

Amino Acid Sequence↗

A multivariate analysis of HIV-1 protease inhibitors and resistance induced by mutation.

This paper describes the use of the multivariate statistical procedure principal component analysis as a tool to explore the inhibitory activity of classes of protease inhibitors (PIs) against HIV-1 viruses (wild type and more-frequent single mutants, V82A, V82F, and I84V) and against protease enzymes. The analysis of correlations between biological activity and molecular descriptors or similarity indexes allowed a reliable classification of the 51 derivatives considered in this study. The best results were obtained in the case of the I84V mutant for which a high number of predictions was achieved. On this basis, this statistical approach is proposed as a reliable method for the prediction of the activity of PIs, for which the data against mutant strains have not been reported.

Drug Resistance, Viral↗

Disentangling conformational states of macromolecules in 3D-EM through likelihood optimization.

Although three-dimensional electron microscopy (3D-EM) permits structural characterization of macromolecular assemblies in distinct functional states, the inability to classify projections from structurally heterogeneous samples has severely limited its application. We present a maximum likelihood-based classification method that does not depend on prior knowledge about the structural variability, and demonstrate its effectiveness for two macromolecular assemblies with different types of conformational variability: the Escherichia coli ribosome and Simian virus 40 (SV40) large T-antigen.

Antigens, Polyomavirus Transforming↗

Common evolutionary origin of aquareoviruses and orthoreoviruses revealed by genome characterization of Golden shiner reovirus, Grass carp reovirus, Striped bass reovirus and golden ide reovirus (genus Aquareovirus, family Reoviridae).

Full-length and partial genome sequences of four members of the genus Aquareovirus, family Reoviridae (Golden shiner reovirus, Grass carp reovirus, Striped bass reovirus and golden ide reovirus) were characterized. Based on sequence comparison, the unclassified Grass carp reovirus was shown to be a member of the species Aquareovirus C. The status of golden ide reovirus, another unclassified aquareovirus, was also examined. Sequence analysis showed that it did not belong to the species Aquareovirus A or C, but assessment of its relationship to the species Aquareovirus B, D, E and F was hampered by the absence of genetic data from these species. In agreement with previous reports of ultrastructural resemblance between aquareoviruses and orthoreoviruses, genetic analysis revealed homology in the genes of the two groups. This homology concerned eight of the 11 segments of the aquareovirus genome (amino acid identity 17-42%), and similar genetic organization was observed in two other segments. The conserved terminal sequences in the genomes of members of the two groups were also similar. These data are undoubtedly an indication of the common evolutionary origin of these viruses. This clear genetic relatedness between members of distinct genera is unique within the family Reoviridae. Such a genetic relationship is usually observed between members of a single genus. However, the current taxonomic classification of aquareoviruses and orthoreoviruses in two different genera is supported by a number of characteristics, including their distinct G+C contents, unequal numbers of genome segments, absence of an antigenic relationship, different cytopathic effects and specific econiches.

Amino Acid Sequence↗

Detection of the prototype of a potential novel genus in the family Papillomaviridae in association with canine epidermodysplasia verruciformis.

Epidermodysplasia verruciformis (EV) is a rare human genetic predisposition to develop flat warts, some of which subsequently undergo cancer transformation. Some human papillomaviruses (HPVs), i.e. HPV 5 and 8, have been associated with cancer development as a sequela of EV. As similar diseases have been observed in dogs, it was hypothesized that unknown canine papillomaviruses (CPVs) may exist and that they may be present in cases of canine EV. Consequently, DNA was extracted from a malignant lesion of a dog with EV and circular DNA was amplified by multiple-primed rolling-circle amplification (RCA). Indeed, sequence determination and analysis of the RCA-amplified and cloned DNA from a malignant canine EV lesion resulted in the detection and primary description of a third CPV (CPV3). Typical papillomavirus genes were identified, with deduced amino acid similarities ranging from 20 to 57 % for E1, E2, E6, E7, L1 and L2, respectively. According to the sequence of the L1 gene, which is used for papillomavirus classification, the new isolate meets the majority of criteria needed to declare detection of a novel genus among the papillomaviruses. Thus, CPV3 may represent the prototype of this novel genus. As the novel virus was found in a dog in association with lesions reminiscent of human EV, it should be interesting to test in the future whether this condition can be reproduced in experimental animals. If such were the case, a new model for EV could be established.

Animals↗

The medically important aerobic actinomycetes: epidemiology and microbiology.

The aerobic actinomycetes are soil-inhabiting microorganisms that occur worldwide. In 1888, Nocard first recognized the pathogenic potential of this group of microorganisms. Since then, several aerobic actinomycetes have been a major source of interest for the commercial drug industry and have proved to be extremely useful microorganisms for producing novel antimicrobial agents. They have also been well known as potential veterinary pathogens affecting many different animal species. The medically important aerobic actinomycetes may cause significant morbidity and mortality, in particular in highly susceptible severely immunocompromised patients, including transplant recipients and patients infected with human immunodeficiency virus. However, the diagnosis of these infections may be difficult, and effective antimicrobial therapy may be complicated by antimicrobial resistance. The taxonomy of these microorganisms has been problematic. In recent revisions of their classification, new pathogenic species have been recognized. The development of additional and more reliable diagnostic tests and of a standardized method for antimicrobial susceptibility testing and the application of molecular techniques for the diagnosis and subtyping of these microorganisms are needed to better diagnose and treat infected patients and to identify effective control measures for these unusual pathogens. We review the epidemiology and microbiology of the major medically important aerobic actinomycetes.

AIDS-Related Opportunistic Infections↗

Hematologic abnormalities and outcome of 16 cats with myelodysplastic syndromes.

We investigated the hematologic abnormalities and prognoses in 16 cats with myelodysplastic syndromes (MDS). Nonregenerative anemia, thrombocytopenia, and neutropenia were observed in 15, 13, and 4, respectively, of the 16 cats with MDS. Morphologic abnormalities characteristic of MDS included megaloblastoid rubricytes (9 cats), hyposegmentation of neutrophils (7 cats), nuclear abnormality of rubricytes (10 cats) and neutrophils (13 cats), and micromegakaryocytes (10 cats). Disease in these 16 cats was subclassified into refractory anemia (RA; 8 cats), RA with excess of blasts (RAEB; 5 cats), RAEB in transformation (RAEB in T; 1 cat), and chronic myelomonocytic leukemia (CMMoL; 2 cats), according to the human French-American-British (FAB) classification. In the cats in which the clinical outcome was known, 3 of 6 cats with high blast cell count MDS, including RAEB, RAEB in T, and CMMoL, developed acute myeloid leukemia, but only 1 of 8 cats with low blast cell count MDS (RA) developed acute myeloid leukemia. Based on the Dusseldorf scoring system for the prognosis of human MDS, the survival times of the cats showing high scores (> or =3 points) were significantly shorter than those of the cats with low scores (<3 points). The FAB classification and Dusseldorf scoring system were considered to be useful for predicting the prognosis of feline MDS. Furthermore, 15 of the 16 cats with MDS in this study were infected with feline leukemia virus, indicating its possible etiologic role in the pathogenesis of feline MDS.

Anemia↗

[Analysis of 18 cases of postpartum haemorrhagic shock in pregnancy with virus hepatitis].

In this article, 147 pregnancies with virus hepatitis admitted to our hospital from Dec 1987 to Jun 1991 were studied. The incidences of postpartum haemorrhage and haemorrhagic shock were 36.05% and 12.24% respectively, and were related to the clinical classification of the hepatitis, with a difference of high significance (P less than 0.01). Analysis of the clinical manifestations and results of the blood tests in 18 cases of shock suggested that the main cause of shock was hepatitis resulting in injury of the liver and thus absence of clotting factors increasing postpartum haemorrhage. Therefore, emphases on antenatal care by keeping the women under the monitoring by obstetrician and physician together. Replenishing clotting factors, rectifying clotting defects; preventing acute hepatitis from proceeding to severe hepatitis and pregnancy-induced hypertension are keys to treat antenatal hepatitis. Close intrapartum care and shortening the duration of labor, especially the third stage, are important to reduce postpartum haemorrhagic and prevent occurrence of haemorrhagic shock.

Adult↗

Diarrhea caused by a slow-growing Enterococcus-like agent in neonatal rats.

An enteropathogenic Enterococcus-like agent was isolated from a spontaneous outbreak of diarrhea that occurred in a colony containing neonatal rats. Diarrhea was experimentally reproduced in virus-antibody-free neonatal rats inoculated with this purified "enterococcus." Gram-positive cocci were adhered to the small intestinal villi of affected animals from which the organism was reisolated. The isolate's classification in the genus Enterococcus was confirmed by genetic probe; however, because of its unique fermentation pattern, it could not be definitively speciated. Indirect immunofluorescence assays indicate that this strain of enterococcus and Enterococcus hirae, another strain pathogenic for neonatal rats, differ antigenically. Enterococci should be considered as potential etiologic agents in outbreaks of diarrhea involving neonatal rats and future efforts directed to increasing our understanding of the pathophysiology of this disease.

Animals↗

HTLV-III exposure among drug users.

The Centers for Disease Control hierarchical classification of those at risk for acquired immunodeficiency syndrome (AIDS) underestimates the number of cases in which illicit drug use may play a role in the exposure to human T-cell leukemia virus type III. The immunosuppressive effects of nitrite inhalants are not sufficiently documented to elucidate their role as a cofactor in the development of AIDS. The currently available data on the immunosuppressive effects of self-administered parenteral drugs and their diluents indicate an associated elevation of immunoglobulin M, depressed helper/suppression T-cell ratios, and even damage to DNA. Illicit psychoactive drugs and their diluents may influence the virulence of the virus among parenteral drug users. An association between parenteral drug use and prostitution is not unexpected. Female prostitutes who use parenteral drugs may be at high risk for exposure to the virus and thus may transmit this infectious agent to their clients and their families.

Acquired Immunodeficiency Syndrome↗

[Equilibrium and auditory disorders in patients affected by HIV-1].

It is thought that about 10% of the patients with advanced human immunodeficiency virus (HIV) infection have otoneurological symptoms, although up to 41% of these patients have general otorhinolaryngological symptoms. The otological changes may be divided into those of balance and those of hearing, to improve classification, although these symptoms are often to be found together in the same patient. We studied 30 seropositive patients with stage II and stage III disease, carrying out studies of oculomotricity, electronystagmography and audiometry (both conventional and high frequency). Oculomotricity changes were seen in 27% of the patients, whilst the caloric test were mainly normal. Conventional audiometry was normal, but high frequency audiometry showed neurosensorial deafness in 23% of the patients. These findings indicate probable changes in the vestibular and oculomotor pathways, with little change in the peripheral sensor for balance.

Acquired Immunodeficiency Syndrome↗

Structural, antigenic and immunogenic relationships between European brown hare syndrome virus and rabbit haemorrhagic disease virus.

The capsid protein of a French isolate of the European brown hare syndrome virus (EBHSV) was expressed in the baculovirus system. The recombinant EBHSV (rEBHSV) capsid protein was able to self-assemble into virus-like particles (VLPs). The VLPs were indistinguishable from the infectious EBHSV and displayed morphological characteristics similar to those we have described for the VLPs resulting from the expression of the capsid protein of rabbit haemorrhagic disease virus (RHDV), a closely related calicivirus. Cross-protection experiments showed that vaccination with rEBHSV particles did not protect rabbits against an RHDV challenge. A set of monoclonal antibodies (MAbs) was raised against rEBHSV capsid protein and used together with anti-RHDV and anti-EBHSV MAbs produced against native viruses to study the antigenic relationships between the two caliciviruses. All six anti-EBHSV MAbs delineated discontinuous epitopes; two of them reacted with specific surface epitopes and the remaining four reacted with internal epitopes which were also present in rRHDV. All anti-RHDV MAbs were monospecific; three reacted with surface linear epitope(s), two reacted with internal linear epitope(s) and one with a surface conformational epitope. On the basis of all these results, a classification of RHDV and EBHSV as two serotypes of a single serogroup is proposed.

Animals↗