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Transforming growth factor beta is a growth-inhibitory cytokine of B cell lymphoma in SIV-infected macaques.

Cytokine dysregulation is accepted as one of the pivotal factors in the pathogenesis of B cell lymphomas in HIV-positive patients. So far no data exist on inhibitory cytokines in the regulatory network of HIV-associated B-NHL. Simian immunodeficiency virus (SIV)-infected macaques are a well-established in vivo model of HIV infection in humans. We used this model for the identification of TGF-beta as a growth-inhibitory cytokine of SIV-associated B cell lymphomas. Fifty-seven rhesus macaques were infected with SIVmac. Nine animals developed B cell lymphomas: eight with high-grade lymphomas of the immunoblastic, centroblastic, and "Burkitt-like" type, and one with the centroblastic/centrocytic type according to the Kiel classification. Six of seven analyzed lymphomas were infected with the macaque EBV, herpes virus macaca mulatta (HVMM). The lymphomas and the SIV-associated B cell lymphoma cell line H50 were positive for transcription of the TGF-beta gene. Protein expression and secretion of the active cytokine were proved by immunohistochemistry and ELISA. H50 transcribed the TGF-beta type I and type II receptor (R I/II), betaglycan, and endoglin. Furthermore, all primary lymphoma samples tested were positive for receptor type I/II transcription and protein expression. TGF-beta induced reduction of cell viability by 67% (range, 50-84% and enhanced apoptosis by 69% (range, 33-111%) compared with the control. TGF-beta activity was blocked by a specific anti-TGF-beta antibody. Thus, TGF-beta fulfilled the criteria of a negative autocrine inhibitor in H50. These data identify TGF-beta as a promising candidate as an inhibitory factor in the regulatory network of HIV-associated lymphomagenesis.

Animals↗

Predictive value of the HIV paediatric classification system for the long-term course of perinatally infected children.

BACKGROUND: To compare the Centers for Disease Control and Prevention (CDC) paediatric classification system with the long-term course of perinatal human immunodeficiency virus type 1 (HIV-1) infection. METHODS: Prospective study on 366 perinatally infected children followed-up from birth and checked at least every 2 months. Survival, smoothed hazard, adjusted hazard ratio of death, and transition probabilities in clinical and immunological categories were outcome measures. RESULTS: Survival was 49% (95% CI : 40-58%) at 8 years. The risk of death was high before the age of 2, relatively low between ages 2 and 7, and contained thereafter. Children did not advance through the categories sequentially. Survival at 8 years was 61.7% (95% CI : 49.8-73.6%) in those children who had passed through clinical category A; the hazard ratio of death was 2.5 (95% CI : 1.7-3.8) for 175 (47.9%) children who skipped this category. Transition probability in clinical category B was 39.9% (95% CI : 32.3-45.6%) after one year, but 59.1% (95% CI : 51.4-66.8%) after 5 years. Before 2 years of age, the probability of entry into category C (40%; 95% CI : 35-45%) was higher than that of entry into immunological category 3 (28%; 95% CI : 22-34%). Conclusions The classification system stands comparison with the clinical reality, but the CD4-positive cell thresholds in infancy should be adjusted and category B indicator diseases better distributed to improve their predictive value.

CD4 Lymphocyte Count↗

Chronic vaginal candidiasis in women with human immunodeficiency virus infection.

Twenty-four percent (7/29) of human immunodeficiency virus-infected women seen at Walter Reed Army Medical Center between 1983 and 1986 presented with a history of chronic refractory vaginal candidiasis. In addition to vaginal candidiasis, all patients were found to have oral thrush on physical examination, severe T-helper cell depletion (mean T-helper cell count of 90), and markedly decreased T4/T8 ratios (mean, 0.3); six of seven women were anergic by delayed-type hypersensitivity skin testing. The conditions of six (86%) of these seven women have progressed to acquired immunodeficiency syndrome (WR6 classification). Chronic refractory vaginal candidiasis may be a presenting symptom of human immunodeficiency virus infection. Women with human immunodeficiency virus infection and unexplained oral and vaginal candidiasis are at high risk to develop other opportunistic infections.

Acquired Immunodeficiency Syndrome↗

Foscarnet penetrates the blood-brain barrier: rationale for therapy of cytomegalovirus encephalitis.

Foscarnet (phosphonoformate) is a potent virustatic drug against herpes-like viruses and is widely used in the therapy of cytomegalovirus infections in immunosuppressed patients. To obtain data on its penetration across the blood-brain barrier, we determined concentrations of foscarnet in cerebrospinal fluid and in plasma specimens from 26 patients with human immunodeficiency virus (stages 2 to 6 by Walter Reed Army Institute of Research classification) after a single infusion of 90 mg of foscarnet per kg of body weight and at steady state by electrochemical detection by high-pressure liquid chromatography. Penetration coefficients were correlated with the integrity of the blood-brain barrier. After a single infusion of foscarnet, levels in plasma ranged from 297 to 1,775 micrograms/ml (990 to 5,920 mumol/liter), with a mean of 766 +/- 400 micrograms/ml. Corresponding levels in cerebrospinal fluid were 57 to 225 micrograms/ml (190 to 750 mumol/liter), with a mean of 131 +/- 52 micrograms/ml. The penetration coefficient was 0.05 to 0.72 (mean, 0.23 +/- 0.16). At steady state, mean foscarnet levels in plasma were 464 +/- 219 micrograms/ml (1,553 mumol/liter) and mean levels in cerebrospinal fluid were 308 +/- 155 micrograms/ml (1,023 mumol/liter). The penetration coefficient was 0.66 +/- 0.11. Although penetration coefficients were highly variable after a single administration and at steady state, the concentrations of foscarnet attained in cerebrospinal fluid are sufficient for complete inhibition of cytomegalovirus replication in vitro. In conclusion, we show that foscarnet seems to be the drug of choice for the treatment of cytomegalovirus encephalitis, because it penetrates the blood-brain barrier and is found in the cerebrospinal fluid in virustatic concentrations. Foscarnet might be considered for additive therapy for human immunodeficiency virus encephalitis in combination with zidovudine or dideoxyinosine.

AIDS-Related Opportunistic Infections↗

Paraffin-immunohistochemical analysis of 226 non-Hodgkin's malignant lymphomas in the endemic area of human T-cell leukemia virus type 1.

A study was conducted to evaluate the usefulness of paraffin-immunohistochemistry for histopathological classification of non-Hodgkin's malignant lymphomas (NHML). the phenotypes of lymphoma cells and other cells were examined using 11 monoclonal and 3 polyclonal antibodies by the ABC method on paraffin-embedded tissue sections of 226 cases of NHML, comprising 94 B-cell lymphomas (B-ML) and 132 T-cell lymphomas (T-ML). In 219 NHML cases (96.8%), lymphoma cells reacted with more than one of these antibodies. A set of MB-1, Mx-pan B, L26, LN-1, LN-2 and anti-immunoglobulin light chain antibodies characterized each subtype of B-MLs, categorized according to the Kiel classification. Mantle-zone lymphoma (MzML) was added as one subtype. L26 stained the largest number of B-MLs (82.8%). B-cell chronic lymphocytic leukemia (B-CLL) was labeled most frequently by MB-1. MzML was characterized by reactivity of lymphoma cells with LN-2 and by the appearance of monoclonal immunoglobulin light chain along the cell membrane. Follicle center cell lymphomas were stained by LN-1 and LN-2, although a small number of proliferating cells were labeled by LN-1 in B-CLL, MzML and the immunocytoma lymphoplasmacytic/cytoid variant. MT-1 and/or UCHL-1 showed various degrees of reactivity with the cell membranes of lymphoma cells in 94.8% of T-MLs. Among the T-cell pleomorphic lymphomas of Suchi and Lennert, the adult T-cell leukemia/lymphoma type, defined by stippled heterochromatin distribution and peculiar huge cells, reacted selectively (p less than 0.05) with anti-phosphokinase C antibody. Anaplastic large cell T-ML reacted with a set of Ber H2, LN-2 and Leu M1. In T-zone lymphomas without hyperplastic follicles, angioimmunoblastic lymphadenopathy with dysproteinemia-type T-ML, lymphoepithelioid cell lymphomas and some pleomorphic lymphomas comprising clear large lymphoma cells, there were many intermingling B cells, and their constitution varied. In some lymphoblastic lymphomas of both the T cell and B-cell type, phenotypes of T cells and B cells were expressed. Consequently, it was shown that paraffin immunohistochemistry was useful for the practical histopathological diagnosis of NHML even in the area where human T-cell leukemia virus type 1 is endemic.

Antibodies, Monoclonal↗

Mumps virus neutralizing antibodies do not protect against reinfection with a heterologous mumps virus genotype.

In April 1999, a previously healthy 22-year-old woman was taken ill with fever and bilateral swelling of the parotid glands. A chronic course of disease extending from April to December was found with swelling of the parotid glands, fatigue, low grade fever, episodes of tachycardia and nightswetting. Mumps virus RNA of genotype A character based on the SH (small hydrophobic) protein gene classification was demonstrated in three serum samples collected during the course of clinical disease. Different criteria for reinfection were fulfilled including demonstration of IgG antibodies by ELISA in a preinfection serum sample. The preinfection serum sample of the patient was able to efficiently neutralize the infectivity of a heterologous genotype D strain but was unable to neutralize the homologous genotype A virus. The findings in the present study may offer an explanation of a mechanism behind previously observed vaccine failures and the occurrence of reinfection with heterologous mumps virus strains.

Adult↗

Nomenclature and classification of herpesviruses: a proposal.

The system for naming and classifying herpesviruses proposed in this memorandum is intended for consideration by other workers before a final proposal is made to the International Commission for Nomenclature of Viruses. The proposal is to classify the herpesviruses in species and subspecies. The virus species should carry the name of the family, super-family, suborder, or order naturally infected by this virus. The second part of the name of the virus should be a numerical designation for each type of virus infecting that unit. The subspecies (representing closely related but clearly biologically different herpesviruses isolated from a given unit of animal classification) should be designated with a consecutive letter in addition to the numerical species designation.

Herpesviridae↗

Genomes of the parapoxviruses ORF virus and bovine papular stomatitis virus.

Bovine papular stomatitis virus (BPSV) and orf virus (ORFV), members of the genus Parapoxvirus of the Poxviridae, are etiologic agents of worldwide diseases affecting cattle and small ruminants, respectively. Here we report the genomic sequences and comparative analysis of BPSV strain BV-AR02 and ORFV strains OV-SA00, isolated from a goat, and OV-IA82, isolated from a sheep. Parapoxvirus (PPV) BV-AR02, OV-SA00, and OV-IA82 genomes range in size from 134 to 139 kbp, with an average nucleotide composition of 64% G+C. BPSV and ORFV genomes contain 131 and 130 putative genes, respectively, and share colinearity over 127 genes, 88 of which are conserved in all characterized chordopoxviruses. BPSV and ORFV contain 15 and 16 open reading frames (ORFs), respectively, which lack similarity to other poxvirus or cellular proteins. All genes with putative roles in pathogenesis, including a vascular endothelial growth factor (VEGF)-like gene, are present in both viruses; however, BPSV contains two extra ankyrin repeat genes absent in ORFV. Interspecies sequence variability is observed in all functional classes of genes but is highest in putative virulence/host range genes, including genes unique to PPV. At the amino acid level, OV-SA00 is 94% identical to OV-IA82 and 71% identical to BV-AR02. Notably, ORFV 006/132, 103, 109, 110, and 116 genes (VEGF, homologues of vaccinia virus A26L, A33R, and A34R, and a novel PPV ORF) show an unusual degree of intraspecies variability. These genomic differences are consistent with the classification of BPSV and ORFV as two PPV species. Compared to other mammalian chordopoxviruses, PPV shares unique genomic features with molluscum contagiosum virus, including a G+C-rich nucleotide composition, three orthologous genes, and a paucity of nucleotide metabolism genes. Together, these data provide a comparative view of PPV genomics.

Animals↗

New viewpoint to histological classification of malignant epithelial tumours of nasopharynx.

Malignant tumors of nasopharyngeal epithelium differ clinically depending on the course of disease and applied therapy. They are presented in regard to the sex, age, smoking habits, alcohol usage and nutrition factors. Various studies already showed various etiological-causal links with Epstein-Barr virus (EBV). This leads to diversity of various morphological and histological types of diseases belonging to various classifications. In this work we presented 60 diagnosed and treated cases with malignant tumor of nasopharyngeal epithelium in the Institute for Otorynolaringology and maxillofacial surgery of Clinical Center of Serbia. All of them were pato-histologicaly examined and 24 of them received serological examination in regard to the concept of association between malignant epithelial tumour and EBV. An important correlation between histopathology and serology was found. Finally, the terminology used by WHO classification is not optimal for further histological determination of nasopharyngeal malignancy; therefore we recommend the French classification of C. Micheaua.

Antibodies, Viral↗

A method for classification of HIV exposure category for women without HIV risk information.

An increasing number of cases of human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS) among women is reported to state and territorial health departments without exposure risk information (i.e., no documented exposure to HIV through any of the recognized routes of HIV transmission). Because surveillance data are used to plan prevention and other services for HIV-infected persons, developing methods to accurately estimate exposure risk for HIV and AIDS cases initially reported without risk information and assisting states to analyze and interpret trends in the HIV epidemic by exposure risk category is important. In this report, a classification model using discriminant function analysis is described. The purpose of the classification model is to develop a proportionate distribution of exposure risk category for cases among women reported without risk information. The distribution was estimated based on behavioral and demographic data obtained from interviews with HIV-infected women; the interviews were conducted in 12 states during 1993-1996. Variables used in the analysis were alcohol abuse, noninjection-drug use, and crack use; year of HIV/AIDS diagnosis; age; employment; and region. As a result of the classification procedure, nearly all cases among women with no reported risk were classified into an exposure risk category: 81%, heterosexual contact; and 16%, injection-drug use. These proportions are higher than the current redistribution fractions (calculated from risk reclassification patterns and weighted by demographic characteristics) and reflect the increasing proportion of cases among women attributable to heterosexual contact with an infected partner. This report provides one method that could be applied to HIV surveillance data at the national level to estimate the proportion of cases in exposure risk categories. However, because the study in this report is limited in sample size and geographic representativeness, other models are also needed for adjusting risk exposure data at the national, state, and local levels.

Adult↗

Characterization of the 3'-terminal nucleotide sequence of two Korean isolates of Daphne virus S support its placement as a distinct species of the genus Carlavirus.

This study determined the 3'-terminal nucleotide sequences of two Korean isolates of Daphne virus S (DVS), a tentative member of the genus Carlavirus, causing leaf distortion and chlorotic spot disease symptoms in daphne plants. The 3'-terminal 1,465 nucleotide sequences of the two isolates contained two open reading frames coding for proteins of 36 kDa viral coat protein (CP) and 12 kDa from the 5'-3' end, which is a typical genome structure of the 3'-terminal region of carlaviruses. Both DVS isolates were 98.1% and 93.6% amino acid identical in the CP and 12 kDa, respectively. The CP gene of DVS shares 25.2-55.2% and 42.9-56.1% similarities with that of 19 other carlaviruses at the amino acid and nucleotide levels, respectively. The 3'-proximal 12 kDa gene of DVS shares 20.2-57.8% amino acid identities with that of 18 other members of the genus. The 3' noncoding region of DVS consists of 73 nucleotides with long excluding poly A tract, and shares 69.1-77.1% identities to the known carlaviruses. In the phylogenetic analyses of the two proteins, DVS was closely related to Helenium virus S and Chrysanthemum virus B. This is the first sequence information for the DVS, and further confirms the classification of DVS as a distinct member of the genus Carlavirus.

3' Untranslated Regions↗

Comparative sequence analysis of the hexon gene in the entire spectrum of human adenovirus serotypes: phylogenetic, taxonomic, and clinical implications.

The adenovirus (AdV) hexon constitutes the major virus capsid protein. The epitopes located on the hexon protein are targets of neutralizing antibodies in vivo, serve in the recognition by cytotoxic T cells, and provide the basis for the classification of adenoviruses into the 51 serotypes known to date. We have sequenced the entire hexon gene from human serotypes with incomplete or no sequence information available (n = 34) and performed a comparative analysis of all sequences. The overall sequence divergence between the 51 human serotypes ranged from 0.7 to 25.4% at the protein level. The sequence information has been exploited to assess the phylogeny of the adenovirus family, and protein distances between the six AdV species (A to F) and among individual serotypes within each species were calculated. The analysis revealed that the differences among serotypes within individual species range from 0.3 to 5.4% in the conserved regions (765 amino acids [aa]) and from 1.5 to 59.6% in the variable regions (154 to 221 aa). Serotypes of different species showed an expectedly greater divergence both in the conserved (5.9 to 12.3%) and variable (49.0 to 74.7%) regions. Construction of a phylogenetic tree revealed three major clades comprising the species B+D+E, A+F, and C, respectively. For serotypes 50 and 51, the original assignment to species B and D, respectively, is not in accordance with the hexon DNA and protein sequence data, which placed serotype 50 within species D and serotype 51 within species B. Moreover, the hexon gene of serotype 16, a member of species B, was identified as the product of recombination between sequences of species B and E. In addition to providing a basis for improved molecular diagnostics and classification, the elucidation of the complete hexon gene sequence in all AdV serotypes yields information on putative epitopes for virus recognition, which may have important implications for future treatment strategies permitting efficient targeting of any AdV serotype.

Adenovirus Infections, Human↗

[Clinicopathologic characteristics of primary liver cancer in patients younger than 35 years].

To investigate clinicopathologic characteristics of primary liver cancer (PLC) in young adults, 77 patients younger than 35 years were compared with 603 patients older than 35 years during the same period. In the young patients, PLC showed a low incidence of PLC detected at mass survey (young 15.6% versus older 28.7%, P < 0.05); a low incidence of hepatitis history (young 36.8% versus older 66.3%, P < 0.01); a high incidence of positive hepatitis B virus surface antigen (HBsAg) (young 79.2% versus older 67.6%, P < 0.05); a low incidence of associated cirrhosis (young 64.9% versus older 90.7%, P < 0.01); larger tumor size (PLC > 5cm; young 87.0% versus older 73.0%, P < 0.01); a more advanced stage of the disease in TNM classification (stage III; young 29.9% versus older 18.2%, P < 0.05). It is suggested that hepatitis B virus (HBV) may play an important role in the development of PLC without associated liver cirrhosis in the young patients. A close periodic surveillance of young adults with a positive HBsAg is important to detect PLC at an early stage.

Adolescent↗

The virology of cervical neoplasia: an HPV-associated malignancy.

Human papillomaviruses are present in virtually all cervical cancers and cancer precursors. Understanding the epithelial virology of this group of viruses has greatly influenced current concepts of cervical carcinogenesis, has provided a framework for understanding the biologic basis of many diagnostic criteria, and has led to revised classification schemes, diagnostic testing, and modifications in clinical management. This paper briefly reviews virologic concepts supporting the pathogenetic role of these viruses in cervical neoplasia.

Female↗

[Herpesviridae: classification and structure in 1991].

In 1981, herpesviruses were classified by the International Committee of Taxonomy of Viruses (ICTV, 1) inside the herpesviridae family. Progress in biotechnology and molecular biology during the last 10 yr, has permitted the characterization of new viruses and genomic structures. The objective of this paper is to collect the data found in the literature since 1981, to actualize the description of herpesviridae family.

Animals↗

Sequence and phylogenetic analysis of the cytoplasmic inclusion protein gene of zucchini yellow mosaic potyvirus: its role in classification of the Potyviridae.

The cytoplasmic inclusion (CI) gene of a Singapore isolate of zucchini yellow mosaic virus (ZYMV-S) was sequenced and compared with CI of 14 other potyviruses. In addition to the consensus sequence GAVGSGKST of nucleotide binding motif (NTBM) which is implicated as a membrane-binding component of the RNA helicase complex, five other conserved motifs were found. Phylogenetic trees were constructed from sequence data for the CI and the coat protein. Similar branching patterns obtained from both CI and coat protein analyses suggests that phylogenetic relationship among potyviruses can be determined using the CI. We propose that phylogenetic analysis of CI gene may be used as an alternative approach for the study of evolution within the family Potyviridae.

Amino Acid Sequence↗

Cytopathology in the identification and classification of tombusviruses.

Ten recognized members of the tombusvirus group, including two strains of tomato bushy stunt virus, were compared for their ultrastructural effects in Nicotiana clevelandii, Gomphrena globosa, and Chenopodium quinoa. The cytopathic inclusions known as multivesicular bodies and tonoplast evaginations containing virus particles were induced by all the viruses in all three hosts. Some of the viruses could be differentiated from each other (especially in C. quinoa) by other characters, such as the accumulation of membranes in cell nuclei, or the type of organelle (chloroplasts, mitochondria or peroxisomes) from which multivesicular bodies developed. The usefulness of these characters for virus identification and grouping is discussed.

Cell Nucleus↗

[Biologic factors hazardous to health: classification and criteria of exposure assessment].

Occupational biohazards include not only factors that have long been known (viruses, bacteria, fungi, parasites), but also agents exerting allergic and toxic effects, which are directly responsible for the development of various diseases in many occupational groups. Numerous agents of this group (allergens, microbial toxins, pollen allergens and allergens of animal origin) are components of bioacrosols--potential hazards inducing occupational respiratory diseases among farmers and people involved in other occupations. Contrary to the majority of chemical and physical factors, neither commonly approved criteria for assessing exposure to biological factors, nor threshold values and methodological recommendations are as yet available. The lack of these criteria renders it difficult to implement in Poland and in other countries Directive 2000/54/EC on the protection of workers against the risk of occupational exposure to biohazards, issued by the European Community. The Institute of Rural Medicine in Lublin has drafted the proposals for threshold limit values of occupational exposure to bioaerosols associated with plant and animal dusts, including: mesophilic bacteria, Gram-negative bacteria, thermophilic actinomycetes, fungi and bacterial endotoxins. These proposals could be considered as a starting point for developing appropriate facultative standards that would facilitate the practical implementation of the aforesaid Directive. Meantime it is essential to be strict in following the binding concentration limits of the plant and animal dusts in the air.

Aerosols↗