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Natural history and serologic diagnosis of infants born to human immunodeficiency virus-infected women.

Perinatal transmission of human immunodeficiency virus is thought to occur in 25% to 50% of the offspring of infected women. Standard diagnostic methods do not permit identification of the infected newborns. To assess diagnostic methods and document the natural history of perinatal human immunodeficiency virus infection, 20 children born to human immunodeficiency virus-infected women were followed prospectively for 18 months by measuring antibody titer, Western blot profiles, and antigenemia, and the results were compared with clinical outcome. Endogenous synthesis of anti-human immunodeficiency virus IgG was demonstrated in 6 of the 8 infected children. Four children synthesized IgM against human immunodeficiency virus. Five had demonstrable p24 antigenemia. No significant differences between infected and noninfected children were noted at birth except drug withdrawal, which occurred more frequently in noninfected infants. The incidence of adenopathy, hepatomegaly, and neurologic and immunologic abnormalities in the infected children were compared with noninfected children. The distinguishing illnesses were the opportunistic infections, lobar pneumonia, and failure to thrive. Seven of the 8 infected children had human immunodeficiency virus-mediated disease by 1 year of age (Centers for Disease Control [Atlanta, Ga] P2 classification), and four had acquired immunodeficiency syndrome (Centers for Disease Control P2D). These studies offer an approach to diagnosis of human immunodeficiency virus infection in infants and document the natural history and possible outcomes of infected children.

AIDS Serodiagnosis↗

Complete coding sequences of dengue-1 viruses from Paraguay and Argentina.

We have determined the complete coding sequences of six dengue-1 (DEN-1) viruses isolated from Paraguay and Argentina in 2000 from patients with dengue fever. Sequences of strains 259par00, 280par00, 295arg00, 297arg00 and 301arg00 can encode a polyprotein of 3392 amino acids. Strain 293arg00 circulated as a "wild type+deletion mutant" quasispecies, with a subpopulation characterized by a 3-nucleotide deletion in the NS4A region. This variant, which would encode a three amino acid change in the NS4A protein, was found as a minority population in one additional partially-sequenced isolate from the same outbreak. These six South American strains group into two different clades of the "American-African" DEN-1 genotype-one clade is most closely related to strains isolated from Brazil in 1997, the other to a Peruvian strain isolated in 1991 for which only partial sequence information is available. DEN-1 viruses isolated worldwide comprise at least four different genotypes according to previously defined classification criteria.

Amino Acid Sequence↗

Nodal T-cell lymphoma in an HTLV-I-endemic area: proviral HTLV-I DNA, histological classification and clinical evaluation.

Adult T-cell leukaemia/lymphoma (ATLL) is a human malignancy associated with human T-cell leukaemia virus type I (HTLV-I). The histology usually indicates a pleomorphic type, but is not consistent. To clarify the relationship between the histological classification and prognosis in ATLL, and to confirm the significance of clonal HTLV-I integration, we reclassified 572 cases with nodal T-cell lymphoma in which the T-cell phenotype and/or genotype was confirmed. In all cases the clonal integration of HTLV-I proviral DNA in the lymph nodes was examined by Southern blot analysis. In addition, anti-ATL antigen (ATLA) determination in the serum or PCR analysis of HTLV-I pX amplification in lymph nodes was also performed. 66/313 (21%) cases with ATLA had no evidence of clonal HTLV-I integration. 572 cases were classified into three groups: (A) cases with clonal integration (247 cases), (B) cases with ATLA without clonal integration of HTLV-I proviral DNA (66 cases), (C) cases without ATLA (259 cases). Histologically, groups B and C frequently demonstrated large cell type and angioimmunoblastic lymphadenopathy with dysproteinaemia (AILD) type; however, group A tended to show a pleomorphic type. Clinically, group A showed a poorer prognosis than groups B and C. In conclusion, group A cases were defined as ATLL (HTLV-I-associated T-cell lymphoma), whereas group B was classified as T-cell lymphoma, which had coincidently occurred in HTLV-I infected carriers. The simplified classification of REAL indicated clinical outcome: the prognosis of ATLL was poor, the unspecified type was intermediate, whereas the other types of lymphoblastic, AILD and anaplastic large cell type were all relatively favourable.

Blotting, Southern↗

Phylogenetic analysis of hepatitis C virus isolates and their correlation to viremia, liver function tests, and histology.

Nucleotide sequence analysis of hepatitis C virus (HCV) strains showed substantial variability leading to a classification into several genotypes and subtypes. The data correlating HCV genotypes and subtypes with hepatitis C viremia levels, demographic characteristics of patients (age, mode of transmission, duration of infection), and severity of liver disease are conflicting. The interpretation of several studies is further complicated because the molecular methods used lacked specificity for genotyping/subtyping and underestimated viremia levels, especially in patients infected with HCV genotypes 2 and 3. In the present study we investigated 97 consecutive patients with chronic hepatitis C using molecular "gold standard" methods. HCV subtyping was performed by sequence and phylogenetic analysis of the nonstructural (NS)-5 region and serum HCV-RNA concentration was assessed by a validated genotype-independent quantitative reverse-transcription-polymerase chain reaction assay using an internal RNA standard. Patients infected with subtypes HCV-1b, HCV-2a-c, and HCV-4 were older than patients infected with HCV-1a and HCV-3a. Serum HCV-RNA levels ranged from 1.5 x 10(4) to 1.0 x 10(8) copies/mL with no significant differences between median serum HCV-RNA concentrations in patients infected with different genotypes/subtypes. Although patients infected with HCV-1b were older, no biochemical or histological evidence was obtained that this subtype is associated with more severe liver disease. Furthermore, the present study showed a lack of correlation between the serum HCV-RNA concentration, biochemical parameters, and liver histology. The median serum HCV-RNA levels in patients with chronic persistent hepatitis, chronic active hepatitis, and liver cirrhosis were 5.0 x 10(6) copies/mL, 2.5 x 10(6) copies/mL, and 5.0 x 10(6) copies/mL, respectively. These differences were not significant. In conclusion, using optimized and validated molecular techniques, the present cross-sectional study showed no correlation between HCV genotypes/subtypes, viremia, liver function test results, and histology.

Adult↗

The species concept and its application to tailed phages.

A recently proposed polythetic definition of virus species appears easily applicable to bacteriophages. Criteria for classification of tailed phages are evaluated. Morphology, DNA homology, and serology are the most important criteria for delineation of species, but no single criterion is satisfactory. Dot-blot hybridization and seroneutralization may suggest false relationships by detecting common sequences in the DNA of otherwise unrelated phages. Species of tailed phages can be defined by a combination of morphology and DNA homology or serology. A procedure for identification of novel phages is outlined. Phage names should include elements of host names.

Bacteriophages↗

Blood zinc status and zinc treatment in human immunodeficiency virus-infected patients.

We investigated the zinc concentration in blood and the effect of zinc supplementation in 11 male outpatients seropositive for human immunodeficiency virus at stage 5 according to the Walter Reed classification. Zinc concentration was measured in serum, platelets, mononuclear and polymorphonuclear cells, and erythrocytes. There was a significant increase in serum zinc concentration after zinc administration, but the zinc level in blood cells remained unchanged. All patients showed a progressive gain in body weight and a slight elevation in levels of CD4+ cells. No adverse side-effects were noticed.

Adolescent↗

Neovascularization induced by intraocular xenografts of normal, preneoplastic, and neoplastic mouse mammary tissues.

The capacity to induce neovascularization was compared in normal, preneoplastic, and neoplastic mouse mammary tumors from strains with a high incidence of tumors (C3H, C3H-Avy, C3H-AvyfB) by implantation of small biopsy fragments on the iris surface in New Zealand White rabbits. Proliferation of iris blood vessels was studied by: 1) direct, in vivo slit-lamp stereomicroscopy and fluorescein angiography; 2) filling of the microvasculature with colloidal carbon; and 3) histologic examination. Ninety percent of mammary tumor implants elicited iris neovascularization after 48-72 hours, regardless of their histologic classification or the presence or absence of mammary tumor virus. Corticosteroid treatment reduced immediate postoperative inflammation (12-36 hr) but did not abolish subsequent growth of new vessels. Necrotic tumor fragments failed to elicit any neovascular response. In contrast, only 6% of normal tissues from resting mammary glands caused any vasoproliferation. Hormone-stimulated mammary tissues from pregnant and lactating mice exhibited a transient neovascular capacity that was lost during postweaning involution. Of the implants from premalignant hyperplastic alveolar nodules (HAN's), 30% produced a pattern of vessel growth similar to that of tumor implants. D-1 line (HAN outgrowth) tissues, which have a predicted low incidence of tumors, induced significantly fewer neovascular responses (P less than 0.002) than morphologically and biochemically similar D-2 line tissues, which have a predicted high incidence of tumors. These data suggest that the capacity to induce neovascularization is acquired during malignant progression of mouse mammary tissues; therefore, demonstration of this property may be useful in the identification of those intermediate populations most at risk for neoplastic transformation.

Animals↗

Dynamic genome organization and gene evolution by positive selection in geminivirus (Geminiviridae).

Geminiviruses (Geminiviridae) are a diverse group of plant viruses differing from other known plant viruses in possessing circular, single-stranded DNA. Current classification divides the family into three subgroups, defined in part by genome organization, insect vector, and plant host range. Previous phylogenetic assessments of geminiviruses have used DNA and/or amino acid sequences from the replication-associated and coat protein genes and have relied predominantly on distance analyses. We used amino acid and DNA sequence data from the replication-associated and coat protein genes from 22 geminivirus types in distance and parsimony analyses. Although the results of our analyses largely agree with those reported previously, we could not always predict viral relationships based on genome organization, plant host, or insect vector. Loss of correlation of these traits with phylogeny is likely due to improved sampling of geminivirus types. Unrooted parsimony trees suggest multiple independent origins for the monopartite genome. genome organization is therefore a dynamic character. Estimates of nonsynonymous and synonymous nucleotide substitutions for extant and inferred ancestral sequences were used to evaluate hypotheses that the replication-associated and coat protein sequences evolve to accommodate plant host and insect vector specificities, respectively. Results suggest that plant host specificity does not solely direct replication-associated protein-evolution but that coat protein sequence does evolve in response to insect vector specificity. Genome organization and, possibly, plant host specificity are not reliable taxonomic characters.

Animals↗

Increasing diversity of HIV-1M serotypes in French blood donors over a 10-year period (1985-1995). Retrovirus Study Group of the French Society of Blood Transfusion.

OBJECTIVE: Phylogenetic analysis of gene sequences of HIV-1 has led to the classification of isolates into a major group (M) of viruses, itself divided into subtypes (A to I), and a minor group (O) of rare isolates. Subtype B viruses are the most prevalent in Western countries but little is known about the dynamics of diffusion of the other subtypes in these regions. The prevalence of B subtypes and non-B subtypes in French blood donors between 1985 and 1995 was evaluated. METHODS: A retrospective study was conducted in 490 blood donors, identified as positive for antibody to HIV-1, by twelve French blood banks between 1985 and 1995. Serological subtyping was performed with a subtype-specific enzyme immunoassay, the reliability for genotyping of which has been demonstrated previously. RESULTS: Of 450 typable samples, 48 (10.7%) were non-B subtypes. Non-B reactive samples were found in all of the regions. An increasing prevalence of individuals infected by non-B viruses was observed, from approximately 4% in the early period to more than 20% in 1994-1995 (P = 0.0004). Non-B viruses did not appear to be restricted to patients with direct or indirect epidemiological links to non-European populations. CONCLUSION: We observed an increasing diversity of HIV-1 strains in the population of blood donors residing in France. This stresses the necessity to broaden the surveillance of HIV-1 diversity in order to improve measures to prevent HIV-1 infections.

Adult↗

Neutralization of primary human immunodeficiency virus type 1 isolates by the broadly reactive anti-V3 monoclonal antibody, 447-52D.

Human monoclonal antibody 447-52D binds to the V3 determinant of the human immunodeficiency virus type 1 (HIV-1) gp120 external glycoprotein. Its binding requires the expression of the GPxR sequence at the center of the V3 domain. HIV-1 variants that are adapted to replication in T-lymphoid cell lines and express this sequence motif are efficiently neutralized by the antibody (M. K. Gorny, A. J. Conley, S. Karwowska, A. Buchbinder, J.-Y. Xu, E. A. Emini, S. Koenig, and S. Zolla-Pazner, J. Virol. 66:7538-7542, 1992). In the present study, the antiviral activity of 447-52D was further defined with regard to its ability to mediate neutralization of primary HIV-1 clinical isolates. Again, the antibody was found to potently neutralize those isolates that expressed the binding sequence. We confirmed that this determinant is commonly expressed by virus isolates belonging to the subtype (clade) B sequence classification. As such, 447-52D may be useful for prophylactic and immunotherapeutic intervention. In addition, the study demonstrated that neutralization of primary HIV-1 isolates is possible if mediated by an appropriate antibody.

AIDS Vaccines↗

New strategies for the diagnosis, treatment, and prevention of herpes simplex in contact sports.

Sports participation may result in myriad cutaneous manifestations, from mundane findings to life-threatening illnesses. Skin infections are among the most common dermatologic ailments in athletes; herpes simplex is clearly among the most serious for the individual athlete, and ultimately the team. Herpes simplex infection most often involves athletes with extensive skin to skin contact. For a variety of reasons, wrestlers and rugby players seem particularly prone. The keys to thwarting epidemics and reducing an athlete's disqualification period include early diagnosis, rapid institution of therapy, and routine systematic preventative measures. This clinical review examines the classification, epidemiology, diagnosis, treatment, and prevention of herpes simplex virus infection as it relates to contact sports. Attention to evidence-based medicine is paid to treatment and prevention techniques. Practical implications for all concerned parties, including athletes, parents, coaches, trainers, and physicians, are discussed.

Acyclovir↗

[Cancer of the penis and its treatment].

It had been believed that carcinoma of the penis was rather rare in the developed countries comparing with that in the under-developing countries, however, the recent epidemiological studies failed to reveal any clear difference of the incidence of carcinoma of the penis all over the world. In these days so called successful treatment is coming to be evaluated by the quality of life (QOL) after surgical or nonsurgical treatment (especially sexual function tended to be considered very important factors altering QOL). I want to emphasize the following issues in this report. 1. Erythroplasia of Queyrat and Bowen's disease are carcinoma in situ and should be dealt as carcinoma of the penis. 2. relation of human papilloma virus and carcinoma of penis. 3. usefulness of TNM classification over Jackson's classification. 4. SCC antigen is a reliable tumor marker of carcinoma of the penis? 5. effectiveness of chemotherapy based on BLM combined with radiation therapy for carcinoma of the penis. 6. usefulness of Mohs microscopically controlled surgery and modified groin dissection. It is generally accepted that since carcinoma of the penis is a rare disease and for one institution up to 50 cases can be experienced during 20 years in Japan, there exist no integrated study involving a large number of institutions. I really wish a certain form of group study to be completed and the results from this study utilized to overcome the present problems for the treatment of carcinoma of the penis.

Antibiotics, Antineoplastic↗

Angiogenic capacity of preneoplastic lesions of the murine mammary gland as a marker of neoplastic transformation.

The angiogenic capacity of normal, preneoplastic, and neoplastic murine mammary tissues from high-tumor-incidence strains (C3H, C3H-AVV, C3H-AVVfB) was compared by implanting small biopsies on the iris surface in New Zealand White rabbits. Proliferation of iris blood vessels was studied by: (a) in vivo slit-lamp stereomicroscopy and fluorescein angiography; (b) colloidal carbon injection of the microvasculature; and (c) histological examination. Ninety % of mammary tumor implants elicited neovascular changes after 48 to 72 hr, regardless of their histological classification or the presence or absence of mammary tumor virus. Corticosteroid treatment did not abolish this response. In contrast, only 6% of implants from normal mammary glands caused any vasoproliferation. Thirty % of implants from premalignant hyperplastic alveolar nodules produced a pattern of vessel growth similar to tumor implants. D-2 line (hyperplastic alveolar nodule outgrowth) tissues, which have a high predicted tumor incidence, induced significantly more neovascular responses (p less than 0.002) than do morphologically and biochemically similar D-1 line tissues, which have a low predicted tumor incidence. These data suggest that angiogenic capacity is expressed during the malignant progression of murine mammary tissues; this property may provide a means for identifying those preneoplastic tissues that are most at risk for cancer.

Adenocarcinoma↗

Lymphoepithelial carcinoma of the stomach with Epstein-Barr virus demonstrated by polymerase chain reaction.

Epstein-Barr virus DNA was detected by polymerase chain reaction in a paraffin-embedded block of an undifferentiated lymphoepithelial gastric carcinoma but was absent in a poorly differentiated gastric adenocarcinoma which also had pronounced lymphoid stroma. This is the first report, to our knowledge, of a lymphoepithelial carcinoma of the stomach. The association with Epstein-Barr virus and the distinctive histologic appearance justify the separate classification of undifferentiated lymphoepithelial carcinomas of the stomach similar to those of the nasopharynx from adenocarcinomas with lymphoid stroma.

Adenocarcinoma↗

Interferon-gamma concentrations are increased in sera from individuals infected with human immunodeficiency virus type 1.

Serum concentrations of interferon-gamma were measured in individuals seropositive for human immunodeficiency virus type 1 (HIV-1). According to the CDC classification system, 6 presented with stage IV-C, 5 with stage IV-A, 8 with stage III, and the remaining 24 individuals with stage II. A modified radioimmunoassay procedure for detection of interferon-gamma was used with a detection limit of 18 U/L. Approximately one-half (22/43) of the seropositives exhibited increased serum interferon-gamma concentrations compared with seronegative blood donors (n = 76). There was a significant association between serum interferon-gamma concentrations and CDC stages of the patients; patients classified as CDC IV-C had the highest concentrations. Further, a significant positive correlation was observed between serum interferon-gamma and serum neopterin concentrations in seropositive study participants. We conclude that interferon-gamma is present in increased concentrations in HIV-1 seropositives compared to seronegative blood donors. Diminished in vitro production of interferon-gamma by T-lymphocytes on stimulation with specific soluble antigens contrasts with increased levels of circulating interferon-gamma in patients.

Acquired Immunodeficiency Syndrome↗

[Atypical profile of markers of hepatitis B and vaccination].

We describe several atypical serological profiles of hepatitis B virus infection (HBV), which can arise difficulties in diagnostic and classification of the infection stage. Its knowledge is important in establishing a more accurate strategy of the screening of blood donors and candidates for vaccination. On the other hand, vaccination may be useful in interpretation of the serological profile. We also discuss the role of HBV mutants in this context.

Biomarkers↗

Genetic and antigenic characterization of novel pestivirus genotypes: implications for classification.

Currently, the genus Pestivirus comprises the four approved species Bovine viral diarrhea virus 1 (BVDV-1), BVDV-2, Classical swine fever virus (CSFV), and Border disease virus (BDV) and one tentative fifth species represented by a single strain (H138) isolated from a giraffe in Kenya more than 30 years ago. To further address the issue of heterogeneity of pestiviruses we have determined the entire N(pro) and E2 coding sequences for several new pestivirus isolates. Interestingly, phylogenetic analysis revealed that one pestivirus isolated in the 1990s in Africa is closely related to strain H138. Moreover, several novel pestiviruses isolated from sheep group together with the previously described strain V60 (Reindeer-1) isolated from a reindeer, whereas one ovine pestivirus strain (Gifhorn) significantly differs from all previously described pestiviruses, including BDV. We propose to term these mainly sheep-derived pestiviruses BDV-2 (V60-like isolates) and BDV-3 (Gifhorn); consequently, the "classical" BDV isolates should be termed BDV-1. As an additional criterion for segregation of pestiviruses, the antigenic relatedness of pestivirus isolates covering all observed major genotypes was studied by cross-neutralization assays. Analysis of the antigenic similarities indicated the presence of seven major antigenic groups corresponding to BVDV-1, BVDV-2, CSFV, BDV-1, BDV-2, BDV-3, and "giraffe". Taking into account the host origin, the lack of differences concerning the course of disease, and the results of our genetic and antigenic analyses, we suggest that BDV-1, BDV-2, and BDV-3 should be considered as major genotypes within the species BDV.

Africa↗

[Clinical classification of adult T-cell leukemia and its complications].

Since human lymphotropic virus, type 1(HTLV-1) associated adult T-cell leukemia (ATL) has various clinical appearances and courses, it is difficult for the clinician to differentiate acute disease which needs immediate treatment from chronic disease which can be observed with no specific treatment. The Lymphoma Study Group of Japan (1984-87) proposed four clinical subtypes: (1) smoldering type; more than 5% of abnormal T-lymphocytes with less than 4000/microliters of lymphocytes in peripheral blood and few abnormal blood chemistry profiles and ATL infiltration, (2) chronic type; absolute lymphocytosis with T-lymphocytosis of more than 4000/microliters, LDH < 2 times the normal upper limit and no hypercalcemia with possible lymph-node, liver, spleen, skin and lung involvement, (3) lymphoma type; no lymphocytosis with less than 1% of abnormal T-lymphocytes, and histologically-proven lymph-node enlargement, and (4) acute type; the patients not classified into any of the above 3 types. The median survival time (MST) was 6.2 months for acute type, 10.2 months for lymphoma type, and 24.3 months for chronic type; 62.8% of smoldering type was still alive up to 4 years. ATL has a poor prognosis because of life-threatening complications including infections and hypercalcemia. Among infectious complications, cytomegalovirus (CMV) is frequently encountered in autopsy patients. It is important to make an early diagnosis since an anti-CMV agent, ganciclovir is now available for clinical use. It takes 10-14 days to culture CMV in vitro, but now rapid diagnosis can be made by direct immunoperoxidase staining with human monoclonal antibodies against an immediate-early antigen. Another major complication is hypercalcemia. The patients' serum and tumor tissues are found to have parathyroid hormone related protein (PTHrP) associated with hypercalcemia. Serum PTHrP (1-34) is determined by radioimmunoassay and its values seem to be correlated with hypercalcemia and the disease activity. There are still many problems to solve for ATL, but recent advances have been made in clinical subtypes and the above 2 complications.

Adult↗