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Viruses detected in the caecum contents of healthy pigs representing a new genetic cluster in genogroup II of the genus "Norwalk-like viruses".

Viruses of the genus 'Norwalk-like viruses' (NLVs) detected in humans have been genetically classified into two major genetic groups, genogroups I and II (GI and GII), which together are made up of at least 14 genetic subgroups. However, a comparable classification of NLVs in other species remains to be carried out. We sequenced a 2-kb region from within the RNA polymerase gene to the 3' end of open reading frame 2 (ORF2) of two NLV strains previously detected in the caecum contents of healthy pigs. The sequences of the entire ORF2 of these two NLV strains were analyzed for their genetic relationships to 15 human strains, which have already been reported and used as references for the genetic classification of human NLV strains, and additional two strains; one, a human strain which has recently been reported and appears to represent a new genetic subgroup of GII; and the other, an animal NLV strain. Analysis of a matrix showing pairwise identities and topology of a neighbor-joining tree showed that the two swine strains could be classified into a new genetic subgroup of GII on the basis of the amino acid sequences of the entire capsid protein. Grouping of the two swine strains was well corroborated by results of similar analyses of nucleotide sequences of the entire ORF2 and of a 510 base region at the 3' end of ORF1.

Animals↗

[Schmidt Ruppin-D-ASV-induced primary rat brain tumor model for therapeutic screening].

It is important to evaluate the therapeutic and side effects of new therapy for malignant brain tumors in an adequate animal model prior to its initial clinical investigation. For decades, neurooncologists have argued for the use of primary, autochthonous tumors rather than transplanted tumors such as C 6 glioma cells and 9 L gliosarcoma cells. But unfortunately, no spontaneous animal astrocytomas are currently available as usable models. So we tried to establish the model of primary, autochthonous avian sarcoma virus-induced rat gliomas for experimental chemotherapy and immunotherapy. The present study was undertaken to determine the incidence and histologic pattern of tumors and the mean survival time of the animal model used. It was found that the intracerebral inoculation of 2 X 10(6) FFU/5 microliter of infectious cell free homogeneous subgroup D Schmidt-Ruppin avian sarcoma virus (SR-D-ASV) into 3-day-old inbred Fischer 344 rats induced small sized tumors in all rats 20 days later. The mean survival time of inoculated rats were 58.7 +/- 12 days. As to the classification of SR-D-ASV induced brain tumors in Fischer rats, astrocytoma was 70.6% (protoplasmic astrocytoma 23.5%, fibrillary astrocytoma 47.1%), sarcoma 17.6%, and mixed astrocytoma and sarcoma 11.8%. In conclusion, this SR-D-ASV induced tumor in the rat fulfilled the following criteria for the desirable animal model: (1) Spontaneously arising. (2) Glial origin. (3) Intraparenchymal growth. (4) Uniformly fatal within reasonable time period. Statistic evaluation of the effects of chemotherapy and immunotherapy was considered to be possible.

Animals↗

Erythroleukemia in two cats naturally infected with feline leukemia virus in the same household.

Erythroleukemia was observed in two unrelated cats infected with feline leukemia virus (FeLV) from the same household. Case 1, a 1-year-old neutered male cat developed erythroleukemia (M6) after a diagnosis of myelodysplastic syndrome (MDS-Er) on the criteria of FAB classification of acute leukemias. Case 2, a 1-year-old neutered female cat, which had close contact with Case 1, also developed erythroleukemia (M6Er). In both cases, marked proliferation of erythroid progenitor cells with disproportionally large numbers of immature forms was observed in the bone marrow. In Case 1, neoplastic proliferation of myeloid cells in the bone marrow was also noted at the terminal stage. Combination chemotherapy with daunomycin was partially effective for treatment of these erythroid neoplasias, but did not induce complete remission. Southern blot analysis using exogenous FeLV-specific probes indicated the clonal origin of these hematopoietic tumor cells. Furthermore, the erythroid and myeloid tumor cells in Case 1 were shown to be derived from independent transformed clones. A variant FeLV was shown to be integrated into the tumor cells in Case 1, while a full-length FeLV was found in both cases. Because these erythroid neoplastic diseases occurred in two unrelated cats kept in the same household and these diseases are rare, they may both have been associated with the same FeLV strain.

Animals↗

Identification of a human group C rotavirus in Malaysia.

Stool specimens from 334 infants and young children hospitalized with diarrhea in the General Hospital, Kuala Lumpur, Malaysia between August and November, 1987 were analyzed for the presence of rotavirus double-stranded (ds) RNA by polyacrylamide gel electrophoresis. Of the 334 specimens analyzed, 32 (9.6%) were positive for rotavirus RNA. One specimen (designated G147) exhibited a ds RNA electropherotype profile characteristic of Group C rotavirus and was selected for further characterization. In Northern blot hybridization studies, the gene 5 segment of strain G147 hybridized with a cDNA probe generated from the cloned gene 5 (which encodes the VP6 inner capsid protein that is group specific) of porcine Group C rotavirus strain Cowden, confirming the classification of strain G147 in Group C. The association of Group C rotavirus with diarrheal illness in Malaysia is consistent with earlier studies that suggest a global distribution of this virus and supports the need for additional epidemiologic studies.

Child, Preschool↗

Phylogenetic relationships among adenovirus serotypes.

Phylogenetic comparisons of adenovirus DNA sequences, including the recently completed genomic sequences of Ad40 and Ad12, have been performed in order to investigate the evolutionary relationships among the various serotypes. Phylogenetic trees were constructed from sequence data for the ITR, E1a, E1b, E2a, E3b, major late promoter, hexon, protease, and fiber regions of the genome using programs contained in the PHYLIP (Phylogeny Inference) package. In general the branching pattern of the human serotypes at each locus correlated well with the classification of the human serotypes into six subgenera (A-F). However, a close evolutionary relationship was inferred between Ad4 (the only member of subgenus E) and the subgenus B viruses Ad3, Ad7, and Ad35, and challenges the placement of Ad4 in a subgenus of its own. In addition, the human viruses of subgenera A (Ad12, Ad18, and Ad31) and F (Ad40 and Ad41), as well as the simian adenoviruses SAV16 (SA7) and SAV8 (SV30), all of which are associated with infections of the gastrointestinal tract, were found to cluster together. The results suggest that these viruses have followed a course of evolution distinct from those of the other subgenera which largely infect the respiratory tract. Analysis of genetic variability between the four complete genomic sequences (Ad2, Ad5, Ad12, and Ad40) identified three regions subject to more rapid change, corresponding to the hexon-, fiber- and E3a-coding regions. Genetic variability at the E3a locus is particularly striking and may relate to the pathogenicity of the various serotypes.

Adenoviridae↗

Nucleotide sequence of the 3'-terminal region of the genome confirms that pea mosaic virus is a strain of bean yellow mosaic potyvirus.

The 1,035 nucleotides at the 3'end of the I strain of pea mosaic potyvirus (PMV-I) genomic RNA, encoding the coat protein, have been cloned and sequenced. A comparison of the derived coat protein sequence with those of the bean yellow mosaic virus (BYMV) strains, CS, S, D and GDD, indicates that PMV-I is a strain of BYMV. Sequence comparisons and hybridisation studies using the 3'-noncoding region support this classification. The nucleotide and protein sequence data also suggest that PMV-I and BYMV-CS form one subset of BYMV strains while the other three strains form another.

Amino Acid Sequence↗

Expression of p16/INK4a in posttransplantation lymphoproliferative disorders.

It was recently demonstrated that classification of posttransplantation lymphoproliferative disorders (PT-LPDs) into morphological and molecular categories is clinically relevant. It was also reported that PT-LPD not associated with Epstein-Barr virus (EBV) had a more aggressive course than most lesions associated with EBV. Because the cyclin-dependent kinase inhibitor p16/INK4a has been reported to be frequently inactivated in high-grade lymphomas, we evaluated 17 PT-LPD to determine whether p16/INK4a expression could be correlated to morphology, EBV detection, and a Ki-67 labeling index. We demonstrated that tumors with no p16/INK4a expression (n = 8) had a predominantly monomorphic appearance, and most were EBV negative (respectively, 7/8 and 5/8), whereas lesions with p16/INK4a expression (n = 9) were mostly polymorphic PT-LPD (6/9) (P = 0.049) and associated with EBV (9/9) (P = 0.015). In particular, strong p16/INK4a expression was observed in atypical immunoblasts and Reed-Sternberg-like cells. Furthermore, the proliferation index was significantly higher in tumors lacking p16/INK4a expression than in other lesions (P = 0.0008). In conclusion, down-regulation of p16/INK4a was mostly observed in PT-LPD lesions known to follow more aggressive courses: monomorphic tumors and EBV-negative PT-neoplasms. Conversely, overexpression of p16/INK4a was associated with EBV-positive PT-LPD. While p16/INK4a might play a role in the proliferative rate of LP-LPD, further investigations are needed to assess the clinical relevance of p16/INK4a expression in predicting the evolution of tumors and to explain how EBV could favor p16/INK4a protein accumulation in lesions.

Adult↗

T-cell and NK/T-cell lymphomas in southern Taiwan: a study of 72 cases in a single institute.

In an attempt to better understand the clinicopathologic features of T- and natural killer (NK)/T-cell lymphomas in Taiwan and the distribution and relative frequency of each subtype according to the new WHO classification, the pathology file of a medical center in southern Taiwan during 1989-2002 was retrospectively searched. The results of light microscopy, immunohistochemistry, in situ hybridization for Epstein-Barr virus (EBER), and T-cell receptor (TCR)-gamma chain gene rearrangement were correlated with clinical findings. A total of 72 cases were identified. They were peripheral T-cell lymphoma, unspecified (PTLu; n = 23, 31.9%), NK/T-cell lymphoma (n = 14, 19.4%), anaplastic large cell lymphoma (n = 13, 18.0%), angioimmunoblastic T-cell lymphoma (AITL; n = 9, 12.5%), precursor T-lymphoblastic lymphoma (n = 8, 11.1%), enteropathy-type intestinal T-cell lymphoma (n = 2, 2.8%), adult T-cell leukemia/lymphoma (n = 2, 2.8%), and subcutaneous panniculitis-like T-cell lymphoma (n = 1, 1.4%). The male to female ratio was 1.5:1. Forty patients (55.6%) had extranodal presentation. Eleven cases including 9 of 14 (64.3%) NK/T-cell lymphomas expressed CD56. All 14 NK/T-cell lymphomas are EBER-positive. Seven of nine (77.8%) AITLs expressed CD10. The overall 5-year survival rate was 10.2%. In conclusion, we have characterized a large series of T- and NK/T-cell lymphomas in southern Taiwan, where there is male predominance and poor prognosis. CD56 is a specific but not very sensitive marker while EBER is most reliable for the diagnosis of NK/T-cell lymphoma. CD10 is a useful marker to differentiate AITL from PTLu.

CD56 Antigen↗

Candidemia: a nosocomial complication in adults with late-stage AIDS.

We retrospectively analyzed 13 episodes of candidemia observed between July 1990 and July 1995 in human immunodeficiency virus (HIV)-infected adults. Candidemia was nosocomially acquired by 11 patients, among whom nine had a central venous catheter (CVC). Twelve cases were of stage C2/C3 according to the 1993 classification of the Centers for Disease Control and Prevention. The median CD4+ cell count was 10/mm3 (range, 3-400/mm3). Causative species were Candida albicans in nine episodes and Candida glabrata and Candida krusei in two episodes each. Eleven episodes occurred in 11 patients who had previously received fluconazole (mean total dose, 7.4 g), including the four episodes caused by non-albicans species. Outcome did not differ according to the administered antifungal therapy. CVCs were removed from seven patients (78%). The overall mortality was 38%. Candidemia is a potentially lethal nosocomial complication during late-stage AIDS and can be due to C. albicans and non-albicans strains.

AIDS-Related Opportunistic Infections↗

Nasopharyngeal carcinoma in young patients.

We have reviewed retrospectively the records of 157 patients, less than or equal to 30 years of age with nasopharyngeal carcinoma (NPC) from 218 such cases identified in the tumor registry files of three major teaching hospitals in Taipei, Taiwan. These cases were diagnosed between 1 January 1982 and 31 December 1985, with a minimum follow-up of 2 years. The average age was 25, with a male/female ratio of 1.67. The TNM (tumor size, nodes, metastases) classification of 127 patients showed T1, 22%; T2, 33.1%; T3, 23.6%; T4, 21.3%; N0, 26%; N1, 16.5%; N2, 27.6%; N3, 30%; and M1, 13.4%. Antibody titer to Epstein-Barr virus capsular antigen (EBVCA) were elevated in 45 of 48 patients tested. Of the 29 patients who had hepatitis B (HB) viral survey done 34.5% were positive for HB surface antigen (HBsAg). Of 13 patients with elevated EBVCA antibody who were also tested for HB, six were HBsAg carrier. Actuarial survival rates of 2 and 3 years are 70 and 62%, respectively, among the 90 patients who were followed regularly or to death. HBsAg carriers and patients with M1 disease had a shorter survival time. We concluded that patients less than 30 years of age seemed to have an increased incidence of NPC, compared to that in an earlier report. Our patients frequently presented with advanced stage and poor prognosis. The high rate of HB carrier raises the possibility that HBV may play a role in the carcinogenesis and tumor growth in some NPC patients. Future prospective studies are needed.

Adolescent↗

Prognostic factors of peripheral T-cell lymphoma (PTL): statistical analysis on 30 patients.

Peripheral T-cell lymphoma (PTL) is a distinctive clinical entity, albeit it comprises several diseases with histologically heterogeneous diagnoses. We studied prognostic factors on 30 patients diagnosed and treated at Shikoku Cancer Center Hospital. Clinical findings and laboratory data were evaluated by statistical analysis to investigate the important factors influencing survival duration. Variables influencing survival were stage, leukemic change, bone marrow infiltration (BMI), anti-human T-lymphocyte virus-type I antibody, white blood cell count, and lactate dehydrogenase (LDH). Multivariate analysis revealed high level of LDH and positive BMI as the important factors for short survival. Histological classifications of the Working Formulation and the T-lymphoma classification by Suchi et al. were also evaluated whether these were related with prognosis. Our data revealed that there was no significant relationship between histological subtype and survival duration. The study of prognostic factors provides valuable aids for us to understand the clinical characteristics of PTL patients with various backgrounds.

Adult↗

Nasal-type T/NK lymphomas: a clinicopathologic study of 13 cases.

Natural Killer (NK) cell lymphomas, which include the nasal and the "nasal type" varieties, are defined as angiocentric lymphomas in the revised European American Lymphoma (R.E.A.L.) classification. This group of diseases is rare in the United States and Europe but is more common in Asia and Central America. It is associated with the Epstein-Barr virus (EBV) and its response to treatment and prognosis are usually very poor. The aim of this study was to describe our experience with 13 patients with angiocentric lymphomas seen at The University of Texas M. D. Anderson Cancer Center (UTMDACC) over the last 14 years. Thirteen patients with a diagnosis of nasal NK cell lymphoma were treated at UTMDACC from 1987 to 1999. Eleven patients were treated initially with doxorubicin based chemotherapy with or without radiotherapy. One patient received interferon (IFN)-alpha and vitamin A and another methotrexate, vincristine, L-Asparaginase, and radiotherapy. The median age was 44 years (range 15-76); there were four women and nine men. All patients presented with local disease involving the sinonasal region. Typical immunophenotypes expressing CD2+, CD3- and CD56+ surface markers as well as non rearrangement of T-receptors were present in all patients. Eight patients (62%) responded to therapy; six (46%) with complete response (CR) and two (16%) with partial response (PR). Five patients (38%) were alive, four with no evidence of disease (NED) at 1, 2, 3, and 9 years after treatment, and one patient was alive with disease (AWD) at the time of publication. One patient died while in CR from complications from allogeneic bone marrow transplant. Six patients had disease progression to extranodal sites including: testis (2), central nervous system (2), lung (1), bone marrow (2), liver (2), peripheral blood (2), and skin (2). In conclusion, the response to doxorubicin-containing regimens is inferior to that of patients with other non-Hodgkin's lymphomas and similar prognostic factors. Because the disease is associated with EBV virus in 90%-100% of the cases and the prognosis is poor, innovative therapies should be tried including immunotherapy that targets the expression of EBV by the tumor with or without myeloablative procedures.

Adolescent↗

Recent advances in acquired immunodeficiency syndrome (AIDS)-related lymphoma.

Human immunodeficiency virus-infected patients are at an increased risk for developing both Hodgkin and non-Hodgkin lymphoma when compared with the general population. With the remarkable decrease in the incidence of opportunistic infections since the availability of highly active antiretroviral therapy (HAART), acquired immune deficiency syndrome-related lymphoma (ARL) is now the second most common cancer associated with human immunodeficiency virus after Kaposi sarcoma. Over the last few years, advances in our understanding of the molecular biology of this heterogeneous group of lymphomas have led to the adoption of new classification systems. The prognosis of patients with ARL has improved dramatically with the availability of HAART, and the survival of many of these patients is now comparable to patients in the general population. Apart from the contribution of HAART, this improvement in prognosis can also be attributed to new initiatives in treatment of these patients, such as the use of effective infusional regimens, the feasibility of high-dose therapy with peripheral stem cell rescue for relapsed or refractory disease, and better supportive care. Nonetheless, several controversial issues persist, including the optimal timing of HAART with combination chemotherapy, the role of rituximab when incorporated into treatment regimens, and the optimal therapy for patients with acquired immunodeficiency syndrome-related Burkitt lymphoma. This article reviews the changes in the epidemiology of ARL in the era of HAART, advances in the biology of ARL, new developments in the management of patients with ARL, and several of the controversial issues that oncologists may encounter in the care of these patients.

AIDS-Related Opportunistic Infections↗

[Doppler echocardiography assessment of cardiac abnormalities in parenteral drug addicts].

We studied by Echocardiographic-Doppler 114 consecutive intravenous drugs addicts (IVDA); 91 were positive human immunodeficiency virus (HIV+) and 23 negatives. We classified them in five groups; beginning the negative HIV as group 0, and groups I to IV stratified according the Central Disease Control (CDC) classification. We compared the cardiac abnormalities founded between themselves and a control group presumed healthy persons of similar age. The cardiac cavities dimensions showed a statistic significant increased left ventricular end-systolic and diastolic diameters, right ventricular diameter, posterior wall and interventricular septum thickness and aortic root diameter compared with the control group; but all were in the normal range for age. The left ventricular fractional shortening was statistically different from control group related the other groups, and the group IV related other. The existence and severity of pericardial effusions were directly related to the illness stage. We founded moderate pericardial effusions in 25% patients in the 0 to III groups, increasing until 50% in the group IV. The presence of valvular vegetations, nearly 30% in our series, ought to the IVDA. We did not found relationship between the severity of valvular incompetence and the illness stage. We recorded a excellent correlation between the ratio T4/T8 lymphocytes with the progress of illness and the existence and severity of cardiac abnormalities.

Adult↗

[Disseminated herpes zoster in chronic lymphatic leukemia].

A 73-year-old woman suffering from chronic lymphatic leukemia presented a rare variant of zoster with disseminated eruptions. Ultrastructural negative staining revealed viruses of the herpes group. Herpes simplex was excluded by means of fluorescence-labelled monoclonal antibodies (HSV-1/HSV-2 direct specimen identification/typing test). It is proposed that the conventional classification of zoster into a segmental and a generalized variant should be supplemented.

Aged↗

[Four cases of thymoma associated with pure red cell aplasia].

Thymomas associated with pure red cell aplasia (PRCA) constituted only 3.3% of 122 thymomas treated in our department from 1963 to March, 1995. Four patients with this disease (2 men and 2 women, mean age: 58 years, range: 41 to 66 years old) are reported. Auto-antibodies were found in all 4 cases, increase of T cell in two, suppression of erythropoietin production in one, and antibody to EB virus in one. Operation was performed in all cases (two thymothymectomies, one extended thymothymectomy, and one thymomectomy), and 3 of 4 patients were in the progressive stage of Masaoka's classification (I, III, IVa, and IVb each). As for the pathological findings, mixed type was found in three cases and lymphocyte predominant type in one. Two patients died from radiation pneumonia. As for PRCA, postoperative therapy was effective (100%) in all patients.

Adult↗

[Epidemiologic background and changes in patients infected with human papilloma virus].

Contagion with certain types of HPV was supposed to have a causal relationship with cervical neoplasia of the uterus. The rate of prevalence of HPV was investigated in pre-cancer and cancer patients with uterine cervical smear using virapap or viratype. According to the cytologic classification, among those whose cytology was diagnosed as class I or II, were found a few positive HPV, however, in cases in classes cytology IIIa, III and IIIb, the positive rate turned out to be 22.5, 41 and 72.4%, respectively. About 65% of patients whose post-operative diagnosis was cervical carcinoma, had been found positive in the pre-operative HPV.DNA check up. The statistical profiles of virally infected subjects were regarded as slightly younger females with early onset of menarche. A higher positive rate was found in such groups such as unmarried single and divorced single women, career employees with special skills, housewives and dwellers in residential and commercial sections. The follow up study of HPV infection was checked with subjects with dysplasia, and no case was recognized in which initially HPV negative dysplasia turned to positive during the observation period. But, in about 50% of those checked, initially HPV positive dysplasia turned to negative, during the follow up period. In the cases with long term (more than 8 years) dysplasia which was followed up, only one out of 10 was found to be HPV positive, while in middle term (more than 2 years but less than 8 years) followed up dysplasia, the positive rate was calculated as 47.8%.

Female↗

Analysis of the complete nucleotide sequence of the picornavirus Theiler's murine encephalomyelitis virus indicates that it is closely related to cardioviruses.

Theiler's murine encephalomyelitis viruses (TMEV) are naturally occurring enteric pathogens of mice which constitute a separate serological group within the picornavirus family. Persistent TMEV infection in mice provides a relevant experimental animal model for the human demyelinating disease multiple sclerosis. To provide information about the TMEV classification, genome organization, and protein processing map, we determined the complete nucleotide sequence of the TMEV genome and deduced the amino acid sequence of the polyprotein coding region. The RNA genome, which is typical of the picornavirus family, is 8,098 nucleotides long. The 5' untranslated region is 1,064 nucleotides long (making it the longest in the picornavirus family after the aphthoviruses) and lacks a poly(C) tract. Computer-generated comparison of the 5' and 3' noncoding regions and polyprotein revealed the highest level of nucleotide and predicted amino acid identity between the TMEV and the cardioviruses encephalomyocarditis virus (EMCV) and Mengo virus. The TMEV polyprotein, which appears to be processed like EMCV since the amino acids flanking the putative proteolytic cleavage sites have been conserved, begins with a short leader peptide followed by 11 other gene products in the standard L-4-3-4 picornavirus arrangement. Because of these similarities, we propose that the TMEV be grouped with the cardioviruses. However, since TMEV and EMCV have different biophysical properties and show no cross-neutralization, they most likely belong in a separate cardiovirus subgroup.

Amino Acid Sequence↗