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PubMed1995

Comparison of therapeutic activity of fluconazole and itraconazole in the treatment of oesophageal candidiasis in AIDS patients: a double-blind, randomized, controlled clinical study.

The aim of this study was to assess the role and therapeutic efficacy of two azole antifungal drugs, fluconazole and itraconazole, in the treatment of endoscopically-diagnosed Candida oesophagitis in patients with Acquired Immunodeficiency Syndrome (AIDS). The study considered 120 Human Immunodeficiency Virus (HIV)-positive patients (67 males and 53 females, mean age 27 +/- 5) at their first episode of oesophageal candidiasis diagnosed by endoscopy (Kodsi's grade II endoscopic classification). The patients were double-blindly randomized into 2 groups of 60 patients each according to the pharmacological therapy administered: a) the patients in the first group received fluconazole (100 mg b.i.d. per os); b) the patients in the second group received itraconazole (100 mg b.i.d. per os). In order to evaluate the efficacy of the pharmacological therapy, a clinical examination was performed every week up to the end of the follow-up period (2 months); endoscopic examination was performed at the end of pharmacological treatment (3 weeks). All patients selected for the study gave their informed consent. Complete remission of endoscopic lesions was observed in 45 patients (75%) in the fluconazole group and in 23 patients (38%) in the itraconazole group (p < 0.001); partial remission of endoscopic lesions was observed in 15 patients (25%) in the fluconazole group and in 28 patients (47%) in the itraconazole group (p < 0.05). No response was observed in 9 patients (15%) in the itraconazole group. Complete clinical remission was observed in 47 patients (78%) in the fluconazole group and in 44 patients (73%) in the itraconazole group (p = n.s.); partial clinical remission was observed in 13 patients (22%) in the fluconazole group and in 12 patients (20%) in the itraconazole group (p =- m.s.). No clinical response was observed in 4 patients (7%) in the itraconazole group. No side-effects worthy of note were observed in the patients of either treatment group. The results of this study demonstrated that fluconazole is associated with higher rates of endoscopic and clinical cure than itraconazole, with a statistically significant difference as regards endoscopic cure. Both drugs appear to be safe and well tolerated. Nevertheless, further controlled clinical investigations are needed to improve our knowledge of the therapeutic action of antifungal drugs in the treatment of Candida oesophagitis in HIV disease.

AIDS-Related Opportunistic Infections↗
PubMed1997

HIV-1 subtypes: implications for epidemiology, pathogenicity, vaccines and diagnostics. Workshop Report from the European Commission (DG XII, INCO-DC) and the Joint United Nations Programme on HIV/AIDS.

Forty-three AIDS scientists from Europe, Africa, the United States, Canada, India and China met in Dar es Salaam, Tanzania to discuss the implications of the global variation of HIV (list of participants included in Appendix). This meeting followed an earlier meeting of the Joint United Nations Programme on HIV/AIDS, held in 1996 in Berlin, Germany [1], in which HIV genetic variability was considered in relation to transmissibility. During the Tanzania meeting, available data pertaining to the biological consequences of HIV genetic variation and its ramifications with regard to epidemiology, diagnostics, classification, and vaccine design were systematically reviewed. There was consensus that classification based on genetically defined subtypes provides an important framework for making advances on understanding viral biology and immunology, and for vaccine development. In addition, other groupings of viruses based on immunological and biological characteristics would be also valuable and help to further refine our understanding of the implications of variability. Key elements of the discussion are summarized here in the context of a review of the current literature.

AIDS Vaccines↗
PubMed2006

Crystal structure and mechanistic determinants of SARS coronavirus nonstructural protein 15 define an endoribonuclease family.

The approximately 30-kb coronavirus (+)RNA genome is replicated and transcribed by a membrane-bound replicase complex made up of 16 viral nonstructural proteins (nsp) with multiple enzymatic activities. The complex includes an RNA endonuclease, NendoU, that is conserved among nidoviruses but no other RNA virus, making it a genetic marker of this virus order. NendoU (nsp15) is a Mn(2+)-dependent, uridylate-specific enzyme, which leaves 2'-3'-cyclic phosphates 5' to the cleaved bond. Neither biochemical nor sequence homology criteria allow a classification of nsp15 into existing endonuclease families. Here, we report the crystal structure of the severe acute respiratory syndrome coronavirus nsp15 at 2.6-A resolution. Nsp15 exhibits a unique fold and assembles into a toric hexamer with six potentially active, peripheric catalytic sites. The structure and the spatial arrangement of the catalytic residues into an RNase A-like active site define a separate endonuclease family, endoU, and represent another spectacular example of convergent evolution toward an enzymatic function that is critically involved in the coronavirus replication cycle.

Amino Acid Sequence↗
PubMed2006

Mathematical virology: a novel approach to the structure and assembly of viruses.

Understanding the structure and life cycle of viruses is a fascinating challenge with a crucial impact on the public health sector. In the early 1960s, Caspar & Klug (Caspar & Klug 1962 Cold Spring Harbor Symp. Quant. Biol. 27, 1-24) established a theory for the prediction of the surface structures of the protein shells, called viral capsids, which encapsulate and hence provide protection for the viral genome. It is of fundamental importance in virology, with a broad spectrum of applications ranging from the image analysis and classification of experimental data to the construction of assembly models. However, experimental results have provided evidence for the fact that it is incomplete and, in particular, cannot account for the structures of Papovaviridae, which are of particular interest because they contain cancer-causing viruses. This gap has recently been closed by the viral tiling theory, which describes the locations of the protein subunits and inter-subunit bonds in viral capsids based on mathematical tools from the area of quasicrystals. The predictions and various recent applications of the new theory are presented, and it is discussed how further research along these lines may lead to new insights in virology and the design of anti-viral therapeutics.

Capsid↗
PubMed2003

Herpes simplex virus and Meniere's disease.

OBJECTIVE/HYPOTHESIS: This study was designed to investigate the hypothesis that Meniere's disease is associated with herpes simplex virus (HSV) reactivation in the vestibular ganglion. STUDY DESIGN: Case control study. METHODS: Vestibular ganglia were obtained from archival surgical pathology specimens from patients undergoing vestibular neurectomy for vertigo caused by Meniere's disease. All patients met criteria for classification as definite Meniere's disease according to American Academy of Otolaryngology/Head and Neck Surgery (AAO-HNS) criteria. Control specimens were obtained from willed body donors. Sections from each ganglion were studied for prevalence of viral DNA using a nested polymerase chain reaction designed to amplify the HSV DNA polymerase gene. Quantitative analysis determined the number of viral copies per standard unit of ganglionic DNA. RESULTS: HSV DNA was more prevalent in paraffin embedded ganglia from patients with Meniere's disease (100%) than in fresh-frozen control ganglia (81%) (P =.02). Fixation and paraffin embedding substantially reduced recovery of HSV virus in selected control specimens. Quantitative analysis found no correlation between viral copy number in control ganglia processed frozen versus formalin fixed and paraffin embedded. CONCLUSIONS: HSV is more commonly isolated from vestibular ganglia of patients with Meniere's disease than the general population. The routine histologic preparation of formalin fixation and paraffin embedding significantly altered the quantity of virus detected though not in a predictable manner. The study provides supportive evidence for a viral etiology in Meniere's disease.

Adult↗
PubMed1989

[Immunological analysis of Japanese encephalitis virus using anti-Kamiyama monoclonal antibodies].

Fifteen hybridomas were produced by fusing P3X63Ag8.653 mouse myeloma cells with spleen cells from BALB/c mice immunized with Japanese encephalitis (JE) virus Kamiyama strain. Antigenic analysis of twenty-five strains of JE virus was carried out by hemagglutination inhibition (HI) test with anti-Kamiyama monoclonal antibodies (KAMIMAs). Twenty-one JE virus strains were isolated from various parts of Japan, and four foreign countries. These strains had been isolated from different host between 1935 and 1979. According to the HI test against the five species-specific monoclonal antibodies, the twenty-five JE virus strains were classified serologically as follows: Group A: Kamiyama, Sekiya, Mochizuki, Nishizono, Sasazaki, Mie 44-1, Fukuoka 7101, Fukuoka 7202, Fukuoka 7309, Fukuoka 7311, Fukuoka 7452, Fukuka 7463, Fukuoka 7506, Kumamoto 80679, Chang Mai and JaGAr 02 strains. Group B: Nakayama-RFVL and Nakayama-Yoken strains. Group C: Nakayama-Yakken, Kalinina, G-1 late, JaGAr 01, Beijing 1 and 691004 strains. Group D: Muar strain. These results mostly corresponded with the serological classification by anti-Nakayama-RFVL monoclonal antibodies. Analysis of the biological activities of KAMIMAs revealed that there were no correlations among HI titer, ELISA titer and neutralization titer. Neutralizing and some non-neutralizing monoclonal antibodies protected mice infected with lethal doses of JE virus Kamiyama strain. SDS-PAGE and immunoblotting analysis revealed that three antibodies reacted with a 52.0 kD band under non-reducing conditions and with a 53.0 kD band under reducing conditions, five antibodies reacted with a 52.0 kD band only under non-reducing conditions, and that seven antibodies reacted with a 14.5 kD band under both non-reducing and reducing conditions.

Animals↗
PubMed1987

[Treatment of autochthonous rat brain tumors with chemotherapy and radiotherapy].

The authors tried to establish a model of primary, autochthonous avian sarcoma virus-induced rat glioma for experimental chemotherapy and radiotherapy. It was found that the intracerebral inoculation of 2 X 10(6) FFU/5 microliter of an infectious cells-free homogeneous sub-group D Schmidt-Ruppin avian sarcoma virus into 3-day-old inbred Fischer rats induced brain tumors in all rats. The mean survival time of the inoculated rats was 58.7 +/- 12 days. With regard to the classification of the induced brain tumors in Fischer rats, astrocytoma accounted for 70%. This ASV-induced tumor in rats fulfills the following criteria for a desirable animal model. Spontaneously arising. Glial origin. Intraparenchymal growth. Uniformly fatal within a reasonable time period. In the present study, the therapeutic effects of anticancer drugs, such as ACNU and vincristine were evaluated and additionally, the effect of ACNU used in conjunction with radiation was also evaluated in this model. The mean survival time of rats was prolonged significantly with ACNU (20 mg/kg) or radiation therapy (1,000 rads), respectively, and in cases where ACNU was used together with radiation, the mean survival time was prolonged further still, but not very significantly, in comparison with radiation therapy alone. In conclusion, the ASV-induced rat glioma model was considered to be closely akin to a spontaneous brain tumor in terms of morphology, blood supply and kinetics of the primary tumor. Moreover, the therapeutic sensitivity of this model to anticancer drugs was fairly similar to that of human anaplastic astrocytoma. Considering these observations, this model seems to be an excellent experimental brain tumor model which is useful for evaluating the effect of new therapies against malignant brain tumors.

Animals↗
PubMedDate not supplied

[Viral infections in hospitalized children affected by acute lower respiratory tract disease]

OBJECTIVE: To evaluate the frequency of the main respiratory viruses in hospitalized children affected by acute lower respiratory tract disease at a university hospital. METHODS: This is a prospective trial that included two cohorts of hospitalized children in the period from April to July 1996. The groups were selected according to the presence of lower respiratory tract disease on admission: Group A- with acute disease (history of less than 7 days) and B- without present or recent respiratory disease. The parameters for defining lower respiratory tract disease included physical and/or radiological pulmonary changes. Clinical and radiological criteria were established for the classification of lower respiratory tract diseases in group A. Nasopharyngeal swab was collected from all children on admission for viral detection by cellular cultures and direct immunofluorescence. RESULTS: 201 cases were selected, 126 in group A and 75 in group B. Viruses were identified in 71 children from groupA(56.4%) and only in 3 from group B (4.0%). The predominant agent in group A was respiratory syncytial virus, identified in 66 cases; adenovirus (4) and influenza (1) were detected in other patients. In group B two patients with respiratory syncytial virus and one with adenovirus were identified. The patients from group A affected by respiratory syncytial virus were younger (median age 3 months versus 13 months) and more wheezy on physical examination (78.7%) than the other patients of the group (33.3%). This virus was associated to most of the bronchiolitis cases (84%) and to half of the pneumonia cases (46.4%). CONCLUSION: The authors found a significant presence of viruses in the majority of children hospitalized with acute lower respiratory tract disease. The respiratory syncytial virus was the predominant agent identified. These results are similar to others previously reported both in developed and some developing countries. The authors emphasize that the present study evaluated only partially the possibility of simultaneous infection by other pathogens and that the present protocol was conducted during the season with the highest incidence of respiratory syncytial virus.

Journal Article↗
PubMed1995

Prognostic value of immunological data, in vitro antibody production, and virus culture in vertical infection with HIV-1.

The prognostic value of immunological indices, in vitro antibody production, and virus culture pattern at 3 months of age was estimated in 35 infants infected by HIV-1 from a cohort of 298 babies born to HIV-1 seropositive mothers and followed up from birth. At 1 year old, 15 of these infants were classified as stage P-1 (according to the Centers for Disease Control classification) seven were P-2A, and seven had AIDS. Significantly higher CD8 percentages, lower percentages and absolute value of CD4, and lower CD4/CD8 ratios at 3 months were observed in infants with severe symptoms at 1 year of age when compared with those who were asymptomatic at this age. Seventy seven per cent of infants with a 'rapid' virus culture when 3 months old had developed AIDS or had died by 1 year of age and only 8% of those with 'slow' virus culture had AIDS when 1 year old. Moreover, 100% of those who were asymptomatic at 1 year had a slow virus culture at 3 months. Significant statistical association was found between the virus replication pattern at 3 months and the clinical stage at 1 year of age.

Acquired Immunodeficiency Syndrome↗
PubMed2005

The question of Citrus viroid IV as a cocadviroid.

It has been suggested that Citrus viroid IV (CVd-IV) be classified as a species within the genus Cocadviroid. This relationship was based on the presence of a terminal conserved hairpin (TCH) and absence of a terminal conserved region (TCR) as specific structural motifs in common with isolates of Coconut cadang-cadang viroid (CCCVd) as well as phylogenetic relationships with members of the genus Cocadviroid. Evidence is presented for a "vestigial" TCR in CVd-IV as well as the introduction of the terminal repeat region (TRR) motif and an alternative sequence analysis that suggests a closer phylogenetic relationship of CVd-IV to isolates of Citrus exocortis viroid (CEVd), a species within the genus Pospiviroid than to CCCVd. This position is further supported by the striking similarity of biological properties between CVd-IV and CEVd with the suggestion offered that biological evidence be considered for specific adjustments to any overall classification scheme for viroids.

Base Sequence↗
PubMed2004

Comparison of four regions in the replicase gene of heterologous infectious bronchitis virus strains.

Infectious bronchitis virus (IBV) produces six subgenomic (sg) mRNAs, each containing a 64 nucleotide (nt) leader sequence, derived from the 5' end of the genome by a discontinuous process. Several putative functional domains such as a papain-like proteinase (PL(pro)), main protease (M(pro)), RNA-dependent RNA polymerase (RdRp), and RNA helicase encoded by the replicase gene are important for virus replication. We have sequenced four regions of the replicase genes corresponding to the 5'-terminal sequence, PL(pro), M(pro), and RdRp domains from 20 heterologous IBV strains, and compared them with previously published coronavirus sequences. All the coronavirus 5'-termini and PL(pro) domains were divergent, unlike the M(pro) and the RdRp domains that were highly conserved with 28% and 48% conserved residues, respectively. Among IBV strains, the 5' untranslated region including the leader sequence was highly conserved (>94% identical); whereas, the N-terminal coding region and the PL(pro) domains were highly variable ranging from 84.6% to 100%, and 77.6% to 100% identity, respectively. The IBV M(pro) and RdRp domains were highly conserved with 82.7% and 92.7% conserved residues, respectively. The BJ strain was the most different from other IBVs in all four regions of the replicase. Phylogeny-based clustering based on replicase genes was identical to the antigen-based classification of coronaviruses into three groups. However, the IBV strain classification based on replicase gene domains did not correlate with that of the type-specific antigenic groups. The replicase gene sequences of many IBVs recovered from infected chickens were identical to those of vaccine viruses irrespective of serotype, suggesting that either there has been an exchange of genetic material among vaccine and field isolates or that there is a convergent evolution to a specific replicase genotype. There was no correlation between the genotype of any region of the replicase gene and pathotype, suggesting that the replicase is not the sole determinant of IBV pathogenicity.

5' Untranslated Regions↗
PubMedDate not supplied

[Morphologic classification of chronic hepatitis].

The diagnosis of chronic hepatitis (CH) should include the information on CH etiology, the presence or absence of CH activity as well as its morphological characteristics. CH may be of a viral etiology (the type of the virus should be mentioned in the diagnosis), autoimmune, drug-induced and alcoholic. The etiology can be established by means of the clinicomorphological analysis using immunological and immunohistochemical techniques. Sometimes it is possible to do so after routine staining of biopsies. Portal, lobular and periportal hepatitis are distinguished morphologically. Instead of the indefinite term chronic persisting hepatitis it is recommended to recognize active and non-active hepatitis.

Biopsy↗
PubMed2006

Autonomous reovirus strain classification using filament-coupled antibodies.

We previously described a filament-based antibody recognition assay (FARA) that generates ELISA-like sandwich structures immobilized on a filament. FARA allows the coupling of antibodies to precise locations along a filament, on-line fluorescence detection of captured pathogen, and feedback-directed filament motion. These properties suggest that this approach might be useful as an automated means to rapidly classify unknown pathogens. In this report, we describe validation of the novel decision tree aspect of this technology using mammalian reovirus. Based on available antibodies, we developed a decision tree algorithm to detect virus with increasing specificity at each level of the tree. Using three strains of reovirus and a bacteriophage control, our system correctly classified the reovirus strains at a concentration of 2 x 10(12) virions ml(-1) and M13K07 phage at 3 x 10(11) virions ml(-1). Classification of reovirus strain type 3 Dearing (T3D) required three levels of testing: general reovirus classification in level 1, serotype 3 classification in level 2, and final T3D strain classification in level 3. Strain T3SA + also required three levels of testing before a final classification was returned in level 3. Classification of strain type 1 Lang (T1L) required two levels of testing. M13K07 phage detection required only one level of testing for classification. These results indicate that automated pathogen classification using FARA is feasible. Furthermore, the simplicity of the design could be exploited for development of more complex sub-classification networks with additional levels and branches.

Antibodies, Viral↗
PubMed1993

Neonatal herpes simplex virus infections.

Neonatal herpes simplex virus infections are a common problem in the United States, occurring at an incidence of one in approximately 3,500 deliveries. In the absence of antiviral therapy significant morbidity and mortality is attendant with disease. Disease manifestations in the newborn include multiorgan involvement (disseminated disease), encephalitis, and/or infection limited to the skin, eye, or mouth. These three broad classifications provide distinctions in severity of disease for evaluation of outcome following antiviral therapy. The availability of antiviral therapy for life-threatening disease, particularly that which is disseminated or involves the brain, has been of particular benefit for children with neonatal herpes. Both acyclovir and vidarabine have proven effective in the management of neonatal herpes simplex virus infection. With current therapeutic modalities, mortality from disease localized to the skin, eye, and mouth is virtually non-existent, yet a few children (approximately 5%) are still at risk for a long-term neurologic sequelae. For babies with encephalitis, the mortality has been reduced to approximately 15% and nearly 50% of survivors develop normally 3 years after treatment. Outcome with disseminated infection is of less value as mortality remains high (50%), but the number of survivors who develop normally is approximately 85%. The introduction of new antivirals with enhanced lipophilicity and, potentially, greater activity in the central nervous system may further improve outcome from this devastating disease.

Acyclovir↗
PubMed2000

Posttransplantation lymphoproliferative disorder: endoscopic findings.

BACKGROUND: Posttransplantation lymphoproliferative disorder (PTLD) may manifest a variety of nonspecific symptoms and must be suspected in the patient who undergoes solid organ transplantation. Common sites of occurrence include the gastrointestinal tract, the central nervous system, and lymphoid tissue of the oral pharynx, mediastinum, and mesentery. The large incidence of gastrointestinal involvement provides an opportunity for endoscopic diagnosis. This is the description of a characteristic endoscopic finding in patients who have undergone liver transplantation who are under evaluation for suspected PTLD. METHODS: During a 2-year period, 27 liver transplantations were performed in 24 pediatric patients. Fourteen patients underwent endoscopic evaluation. Indications for endoscopy included abdominal pain, vomiting, hematemesis, irritability, growth failure, anemia, occult blood loss, and suspected PTLD. Biopsy specimens were obtained from any endoscopically detected abnormality and from the duodenum, gastric antrum, esophagus, terminal ileum, cecum, and rectum. Specimens with suspected PTLD were evaluated with Epstein-Barr virus latent membrane stain. RESULTS: Six patients were found to have a characteristic lesion, which was raised, rubbery, and erythematous, with a central ulceration. Lesions were singular or multiple and ranged from 5 to 15 mm in diameter. Microscopic evaluation revealed a monotonous proliferation of lymphocytes. All specimens were positive for Epstein-Barr virus latent membrane protein stain. Stains for cytomegalovirus were negative. Biopsy specimens from the eight patients without identified characteristic lesions were negative for PTLD. CONCLUSIONS: Panendoscopy is a useful tool for the diagnosis and treatment of gastrointestinal PTLD. Endoscopy is easily accomplished, may provide an instantaneous result if the characteristic lesion is identified, and provides tissue for disease classification. Patients with unexplained gastrointestinal signs or symptoms should undergo panendoscopy for suspected PTLD.

Adolescent↗
PubMed1997

The immunophenotypic characterization of bovine lymphomas.

A prospective analysis of 38 cases of bovine lymphoma was performed. Thirty-five of the lymphomas were considered enzootic because of serologic or molecular biologic association with the bovine leukemia virus (BLV). The three remaining cases were in cattle < 1 year of age and were not associated with BLV and hence were considered sporadic lymphomas. Utilizing the national cancer Institute Working Formulation for the morphologic classification of human non-Hodgkin's lymphoma, 54.3% (19/35) of the enzootic lymphomas were classified as the diffuse large cleaved cell type. The cells of the 35 enzootic lymphomas expressed a consistent immunophenotype represented by MHCII+, gamma-heavy chain+, and lambda-light chain+; this constellation of markers indicated a mature B-cell phenotype. The three sporadic lymphomas failed to express MHCII antigen despite the presence of other B-cell antigens. There was no correlation between morphologic cell type and immunophenotype in these bovine lymphomas.

Animals↗
PubMed1997

Phylogenetic analysis of rabbit haemorrhagic disease and European brown hare syndrome viruses by comparison of sequences from the capsid protein gene.

A 398 bp fragment of the capsid protein (VP60) gene of 39 clinical samples of rabbit haemorrhagic disease virus (RHDV) and 17 of European brown hare syndrome virus (EBHSV), collected between 1981 and 1995 from 17 countries, was amplified by PCR and directly sequenced. The alignment of the nucleotide sequences and the subsequently constructed phylogenetic tree clearly separated RHDV from EBHSV as phylogenetic entities. The nucleotide homology rates between the RHDV and EBHSV groups ranged between 52.6% and 60.0%. The homology rates within the groups were much higher, 89.4% to 100% for the RHDV samples, and 89.4% to 100% for the EBHSV specimens. No intermediate viruses were found. Despite the high homology, three main branches could be identified in the phylogenetic tree of the RHDV samples, corresponding to the epizootiological data, while the EBHSV dendrogram did not show such well defined branches. The present results support the classification of RHDV and EBHSV as two distinct members of the Caliciviridae family. Nevertheless, a comparison with previously determined sequences of other caliciviruses shows that RHDV and EBHSV are more closely related to each other than to any other calicivirus.

Animals↗