bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of Minority Populations of Human Immunodeficiency Virus Type 1 in the Evolution of Viral Resistance to Protease Inhibitors
Authors: Charpentier Charlotte , Dwyer Dominic E. , Mammano Fabrizio , Lecossier Denise , Clavel François , Hance Allan J. 
Published: March 2004

ABSTRACT
Human immunodeficiency virus type 1 (HIV-1) drug resistance results from the accumulation of mutations in the viral genes targeted by the drugs. These genetic changes, however, are commonly detected and monitored by techniques that only take into account the dominant population of plasma virus. Because HIV-1-infected patients harbor a complex and diverse mixture of virus populations, the mechanisms underlying the emergence and the evolution of resistance are not fully elucidated. Using techniques that allow the quantification of resistance mutations in minority virus species, we have monitored the evolution of resistance in plasma virus populations from patients failing protease inhibitor treatment. Minority populations with distinct resistance genotypes were detected in all patients throughout the evolution of resistance. The emergence of new dominant genotypes followed two possible mechanisms: (i) emergence of a new mutation in a currently dominant genotype and (ii) emergence of a new genotype derived from a minority virus species. In most cases, these population changes were associated with an increase in resistance at the expense of a reduction in replication capacity. Our findings provide a preliminary indication that minority viral species, which evolve independently of the majority virus population, can eventually become dominant populations, thereby serving as a reservoir of diversity and possibly accelerating the development of drug resistance.
Protein Kinase B/Akt Regulates Coxsackievirus B3 Replication through a Mechanism Which Is Not Caspase Dependent
Authors: Esfandiarei Mitra , Luo Honglin , Yanagawa Bobby , Suarez Agripina , Dabiri Darya , Zhang Jianchang , McManus Bruce M. 
Published: March 2004

ABSTRACT
The role of signaling pathways including the mitogen-activated protein kinases (MAPKs) and phosphatidylinositol 3-kinase (PI3K) during viral infection has gained much recent attention. Our laboratory reported on an important regulatory role for extracellular signal-regulated kinases (ERK1/2), subfamily members of the MAPKs, during coxsackievirus B3 (CVB3) infection. However, the role of the PI3K pathway in CVB3 infection has not been well characterized. CVB3 is the most common known viral infectant of heart muscle that directly injures and kills infected cardiac myocytes during the myocarditic process. In the present study, we investigated the role of protein kinase B (PKB) (also known as Akt), a general downstream mediator of survival signals through the PI3K cascade, in regulating CVB3 replication and virus-induced apoptosis in a well-established HeLa cell model. We have demonstrated that CVB3 infection leads to phosphorylation of PKB/Akt on both Ser-473 and Thr-308 residues through a PI3K-dependent mechanism. Transfection of HeLa cells with a dominant negative mutant of Akt1 or pretreatment of wild-type HeLa cells with the specific PI3K inhibitor LY294002 significantly suppresses viral RNA expression, as reflected in diminished viral capsid protein expression and viral release. Dominant negative Akt1 and LY294002 also increase apoptosis in infected cells, which can be reversed by addition of the general caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (zVAD.fmk). Interestingly, blocking of apoptosis by zVAD.fmk does not reverse the viral RNA translation blockade, indicating that the inhibitory effect of dominant negative Akt1 on viral protein expression is not caspase dependent. In addition, we showed that the attachment of virus to its receptor-coreceptor complex is not sufficient for PKB/Akt activation and that postentry viral replication is required for Akt phosphorylation. Taken together, these data illustrate a new and imperative role for Akt in CVB3 infection in HeLa cells and show that the PI3K/Akt signaling is beneficial to CVB3 replication.
Rubella Virus Capsid Protein Modulates Viral Genome Replication and Virus Infectivity
Authors: Chen Min-Hsin , Icenogle Joseph P. 
Published: March 2004

ABSTRACT

The structural proteins (SP) of the
Togaviridae
can be deleted in defective interfering RNAs. The dispensability of viral SP has allowed construction of noninfectious viral expression vectors and replicons from viruses of the
Alphavirus
and
Rubivirus
genera. Nevertheless, in this study, we found that the SP of rubella virus (RUB) could enhance expression of reporter genes from RUB replicons in
trans
. SP enhancement required capsid protein (CP) expression and was not due to RNA-RNA recombination. Accumulation of minus- and plus-strand RNAs from replicons was observed in the presence of SP, suggesting that SP specifically affects RNA synthesis. By using replicons containing an antibiotic resistance gene, we found 2- to 50-fold increases in the number of cells surviving selection in the presence of SP. The increases depended significantly on the amount of transfected RNA. Small amounts of RNA or templates that replicated inefficiently showed more enhancement. The infectivity of infectious RNA was increased by at least 10-fold in cells expressing CP. Moreover, virus infectivity was greatly enhanced in such cells. In other cells that expressed higher levels of CP, RNA replication of replicons was inhibited. Thus, depending on conditions, CP can markedly enhance or inhibit RUB RNA replication.
Reptilian Reovirus Utilizes a Small Type III Protein with an External Myristylated Amino Terminus To Mediate Cell-Cell Fusion
Authors: Corcoran Jennifer A. , Duncan Roy 
Published: March 2004

ABSTRACT

Reptilian reovirus is one of a limited number of nonenveloped viruses that are capable of inducing cell-cell fusion. A small, hydrophobic, basic, 125-amino-acid fusion protein encoded by the first open reading frame of a bicistronic viral mRNA is responsible for this fusion activity. Sequence comparisons to previously characterized reovirus fusion proteins indicated that p14 represents a new member of the fusion-associated small transmembrane (FAST) protein family. Topological analysis revealed that p14 is a representative of a minor subset of integral membrane proteins, the type III proteins N
exoplasmic
/C
cytoplasmic
(N
exo
/C
cyt
), that lack a cleavable signal sequence and use an internal reverse signal-anchor sequence to direct membrane insertion and protein topology. This topology results in the unexpected, cotranslational translocation of the essential myristylated N-terminal domain of p14 across the cell membrane. The topology and structural motifs present in this novel reovirus membrane fusion protein further accentuate the diversity and unusual properties of the FAST protein family and clearly indicate that the FAST proteins represent a third distinct class of viral membrane fusion proteins.
High Variety of Different Simian T-Cell Leukemia Virus Type 1 Strains in Chimpanzees (Pan troglodytes verus) of the Taï National Park, Côte d'Ivoire
Authors: Leendertz Fabian H. , Junglen Sandra , Boesch Christophe , Formenty Pierre , Couacy-Hymann Emmanuel , Courgnaud Valerie , Pauli Georg , Ellerbrok Heinz 
Published: March 2004

ABSTRACTWe found human T-cell leukemia virus type 1- and simian T-cell leukemia virus type 1 (STLV-1)-related infections in 5 of 10 chimpanzees originating from three groups of wild chimpanzees. The new virus isolates showed a surprising heterogeneity not only in comparison to STLV-1 described previously in other primate species but also between the different chimpanzee groups, within a group, or even between strains isolated from an individual animal. The interdisciplinary combination of virology, molecular epidemiology, and long-term behavioral studies suggests that the primary route of infection might be interspecies transmission from other primates, such as red colobus monkeys, that are hunted and consumed by chimpanzees.
Thyroid transcription factor 1 in pulmonary adenocarcinoma
Authors: Stenhouse G , Fyfe N , King G , Chapman A , Kerr K M 
Published: March 2004

Aims:To discover whether variations in thyroid transcription factor 1 (TTF-1) staining in different subtypes and patterns of pulmonary adenocarcinoma are related to the putative origin of the tumour. In addition, to confirm the specificity of TTF-1 for pulmonary (as opposed to other sites) adenocarcinoma, to examine the possible prognostic relevance of TTF-1 positivity in lung cancer, and to review this laboratory’s experience of TTF-1 in diagnostic practice.Materials/Methods:In total, 128 primary lung adenocarcinomas, 106 primary non-pulmonary adenocarcinomas, and 37 pulmonary non-adenocarcinoma tumours were studied. In addition, 100 cases where TTF-1 was used in routine surgical pathology practice were investigated. Immunoperoxidase staining was performed on formalin fixed, paraffin wax embedded sections using anti-TTF-1 antibody. Staining was evaluated semiquantitatively using the frequency and intensity of nuclear positivity.Results:None of the 106 non-pulmonary adenocarcinomas expressed TTF-1 and only three of the 37 non-adenocarcinoma lung cancers, all neuroendocrine carcinomas, were positive. Of the pulmonary adenocarcinomas, 75% were strongly positive for TTF-1. Mucinous (two of six) and poorly differentiated adenocarcinomas (four of 10) were less likely to stain. Of the peripheral adenocarcinomas, 33 of 37 were positive, whereas only seven of 14 of those of bronchial origin stained strongly. Atypical adenomatous hyperplasia strongly expressed TTF-1. No “false positives” were encountered in the 100 routine diagnostic cases.Conclusion:Positive TTF-1 staining is useful in the differential diagnosis of pulmonary adenocarcinomas. TTF-1 may be a lineage marker for tumours arising from the peripheral airway or alveolar epithelium and has no prognostic relevance.
Steatosis and fibrosis in patients with chronic hepatitis C
Authors: Wyatt J , Baker H , Prasad P , Gong Y Y , Millson C 
Published: March 2004

Background:Steatosis is present on liver biopsy in approximately 50% of patients with hepatitis C; its association with stage of fibrosis has been reported, but its relation to other fibrosis associated factors is unknown.Aim:To study the relation between steatosis and other histological features in patients with hepatitis C, and changes in steatosis with time.Methods:Cross sectional study: 233 routine liver biopsies from 219 patients with hepatitis C; hepatectomy specimens from 65 patients transplanted for hepatitis C cirrhosis. Longitudinal study: 41 patients with two biopsies and 10 patients with three biopsies performed over 2–8 years. Biopsies were scored by the Ishak scheme, and degree of steatosis assessed subjectively. Multivariate analysis was used to study the interaction of fibrosis associated factors. Changes in steatosis over time in individual patients were explored in the longitudinal study.Results:Steatosis was present in 50% of biopsies. It correlated strongly with fibrosis in non-cirrhotic samples, but declined in cirrhosis, and was unusual in transplant hepatectomy specimens. On multivariate analysis of non-cirrhotic biopsies, steatosis was associated with increasing patient age and remained significantly associated with fibrosis independent of portal inflammation and interface hepatitis. In the longitudinal study, steatosis persisted and increased over time, except in patients developing cirrhosis.Conclusions:Steatosis is associated with fibrosis independently of necroinflammation, but declines in cirrhosis. It may represent a pathogenic pathway distinct from necroinflammatory activity in the generation of liver fibrosis, and should be included in the assessment of biopsies for clinical and research purposes.
Suspicious urinary cytology with negative evaluation for malignancy in the diagnostic investigation of haematuria: how to follow up?
Authors: Nabi G , Greene D , Donnel M O 
Published: March 2004

Aims:To define the natural history of patients with suspicious urinary cytology and negative initial evaluation for malignancy in the investigation of haematuria.Patients and methods:Data from the hospital information support system on urinary cytology examinations carried out at one centre were audited over a period of 24 months. There were 102 patients who had suspicious urinary cytology for malignant cells with negative initial evaluation. Follow up investigations, treatment, and final outcome were noted.Results:There were 102 patients with suspicious urinary cytology and negative initial evaluation for malignancy in 24 months, with a mean follow up of 15.7 months. Seventy patients had no obvious pathology on initial investigations. Forty one patients were found to have urological malignancies (29 bladder, eight ureteric, and four prostate) on follow up. All patients diagnosed as having urothelial malignancies on follow up had either persistent suspicious cytology (29) or recurrent haematuria (eight). The mean duration for appearance of lesions was 5.6 months (range, 3–12 months). Three patients had suspicious digital rectal examination and biopsies confirmed adenocarcinoma of the prostate. One patient had urinary retention and transurethral resection of prostate showed prostatic adenocarcinoma. The presence of suspicious cells on repeat urine analysis was the only significant factor in predicting the presence of urothelial tumours (p  =  0.002).Conclusion:Patients with persistent suspicious/positive cytology or recurrent haematuria need further evaluation and follow up. Asymptomatic patients or patients with obvious benign pathology do not require repeat evaluation. Careful urological evaluation, including prostate, should be carried out in these patients.
The practical application of reflectance spectrophotometry for the demonstration of haemoglobin and its degradation in bruises
Authors: Hughes V K , Ellis P S , Burt T , Langlois N E I 
Published: March 2004

Aims:To develop a non-invasive method to demonstrate the presence of haemoglobin and its degradation products in bruises in live human subjects for the purposes of objectively assisting in the determination of the age of a bruise.Methods:The cuvette holder unit of a Cary 100 Bio UV-Visible Spectrophotometer was replaced with the manufacture’s fibre optic cable and optical reflectance probe. The probe was placed on the skin surface. The absorption spectrum from 780 to 380 nm was collected and transformed into the first derivative. Calculation of the first derivative permits absorption attributed to haemoglobin degradation (primarily to bilirubin, but also haemosiderin) to be separated from absorption by haemoglobin. First derivative and colorimetry values, expressed as CIEL*a*b data, were derived from scans of 50 bruises.Results:The fibre optic cable and probe allowed the spectrophotometer to collect reproducible absorption spectra of bruises in the skin of living subjects. A bruise at three days has greater negative first derivative values at 480 and 490 nm than does a fresh bruise, indicating the local degradation of haemoglobin. Correlation between the first derivative and the CIEL*a*b “b” values in a series of bruises indicates that the yellow colour in a bruise is proportional to the amount of local haemoglobin breakdown.Conclusion:The ability to demonstrate the presence of haemoglobin and measure its degradation in bruises in living human subjects by a non-invasive method has not been described previously, and may be of use in the objective ageing of bruises for forensic purposes.
Unfavourable prognosis of patients with trisomy 18q21 detected by fluorescence in situ hybridisation in t(11;18) negative, surgically resected, gastrointestinal B cell lymphomas
Authors: Krugmann J , Tzankov A , Dirnhofer S , Fend F , Greil R , Siebert R , Erdel M 
Published: March 2004

Background:The most frequent cytogenetic alteration in gastrointestinal (GI) B cell lymphoma (BCL) is t(11;18)(q21;q21). GI B cell non-Hodgkin lymphomas lacking this translocation vary in their biology and clinical outcome. The t(11;18) negative subgroup shows increased numerical changes of chromosome 18, although its clinical relevance remains unknown.Methods:Thirty surgically resected primary GI BCLs were examined—11 low grade marginal zone mucosa associated lymphoid tissue (MALT) lymphomas, four marginal zone lymphomas with diffuse large BCL (DLBCL), and 15 de novo DLBCLs. Chromosome 18 aberrations were examined using interphase fluorescence in situ hybridisation. Trisomy 18 was studied applying a centromere 18 probe and a dual colour probe for the MALT1 gene at 18q21.Results:Using the MALT1 probe, only one marginal zone MALT lymphoma had a break apart pattern, indicating t(11;18) or variants. In the GI BCLs lacking MALT1 breaks, trisomy 18q21 was seen in seven patients (four with complete trisomy 18 and three with partial trisomy of 18q21). Trisomy 18q21 was found in two of 10 low grade MALT lymphomas and five of 19 GI BCLs with large cell component. Six of 17 patients with trisomy 18q21 presented with ≥stage II and one of 12 with stage I disease. Trisomy 18q21 was associated with significantly shorter disease specific survival in the whole group and GI BCLs with large cell component, but not in the low grade group.Conclusions:Trisomy 18q21, including MALT1, may be associated with advanced tumour stage and may be a predictor of poor outcome in surgically resected primary GI BCLs.
Serological and genetic characterisation of a unique strain of adenovirus involved in an outbreak of epidemic keratoconjunctivitis
Authors: Adhikary A K , Inada T , Banik U , Mukouyama A , Ikeda Y , Noda M , Ogino T , Suzuki E , Kaburaki T , Numaga J , Okabe N 
Published: March 2004

Aims:To characterise a novel strain of adenovirus (Ad) type Ad8 (genome type Ad8I) involved in an epidemic keratoconjunctivitis (EKC) outbreak in Hiroshima city using serological testing and sequence analysis of the fibre and hexon gene.Methods:A neutralisation test (NT) was performed in microtitre plates containing a confluent monolayer of A549 cells using 100 tissue culture infectious doses of virus and type specific antisera. The haemagglutination inhibition test was also carried out in microtitre plates with rat erythrocytes using four haemagglutination units of virus and twofold dilutions of serum. The fibre gene was sequenced by generating overlapping polymerase chain reaction products or by direct sequencing of genomic DNA. Primer selection was based on alignment of the fibre genes of human adenovirus serotypes Ad8, Ad19, Ad37, Ad9, and Ad15 available from Gene Bank.Results:The virus strain was specifically neutralised by anti-Ad8 antibodies, although there was a major crossreaction with anti-Ad9 antibodies. Haemagglutination was equally inhibited by anti-Ad8 and anti-Ad9 antibodies. The predicted amino acid sequences of the hypervariable regions (HVRs) of the Ad8I hexon gene showed higher homology with Ad9 (83.3%) than with Ad8 (62.0%). However, the Ad8I fibre knob was more homologous to Ad8 (94.4%) than to Ad9 (91.6%).Conclusions:Ad8I is a unique strain of adenovirus because of its lower genomic homology with Ad8, major crossreactivity with Ad9 in NT, and mixed genetic organisation of HVRs of the hexon gene. These factors may have enabled the virus to circumvent acquired immunity, resulting in the outbreak.
Loss of heterozygosity of the BRCA1 and FHIT genes in patients with sporadic breast cancer from Southern Brazil
Authors: Santos S C L , Cavalli L R , Cavalli I J , Lima R S , Haddad B R , Ribeiro E M S F 
Published: March 2004

Aim:The evaluation of allelic losses at the FHIT and the BRCA1 genes and at three other loci at the 17q region in a series of 34 sporadic breast cancer cases from Southern Brazil.Methods:The samples were evaluated for loss of heterozygosity (LOH) at the FHIT and the BRCA1 genes and at three other microsatellite markers at 17q, and the findings were correlated with clinicopathological parameters.Results:The BRCA1 intragenic marker, D17S855, had the highest frequency of LOH, detected in 10 of 24 informative cases, followed by the D17S579 (six of 23 informative cases), D17S806 (five of 21 informative cases), and D17S785 markers (five of 21 informative cases). LOH at the FHIT intragenic marker, D3S1300, was found in six of 25 informative cases. In four of the six cases with LOH of the FHIT gene, there was concomitant loss of the BRCA1 intragenic marker.Conclusions:The frequency of allelic losses in the FHIT and BRCA1 loci in the Southern Brazilian population is similar to that described in the general population. No correlations were found when the total LOH frequency was compared with tumour size, grade, or presence of axillary lymph node metastasis. Further studies using larger sporadic breast cancer samples and additional markers would be useful to confirm these findings, in addition to establishing more specific associations with clinicopathological parameters in this specific population.
An audit of splenectomies in a teaching hospital in North India. Are postsplenectomy guidelines being complied with?
Authors: Deodhar M , Kakkar N 
Published: March 2004

Aims:Patients with an absent or dysfunctional spleen are at risk of infection by encapsulated and other bacteria. Overwhelming postsplenectomy infection (OPSI) causes most concern because it can result in significant mortality. A retrospective review of splenectomised patients in a tertiary care setting over an eight year period was carried out to determine whether current postsplenectomy guidelines were being followed.Methods:The cases were identified from the medical records and pathology files and data such as the reason for splenectomy, the preventive measures taken regarding vaccination, and antibiotic prophylaxis, together with their documentation in the discharge notes were assessed.Results:Fifty six patients were studied. Trauma, both blunt and penetrating, was the most common reason for splenectomy. Thirty six patients received pneumococcal vaccination, with 20 patients having no mention of vaccination in their case notes. The discharge notes of 50 patients mentioned their splenectomised status; however, documentation of vaccination details in the discharge summary was poor, with only three patients having the relevant information recorded. Documentation of the need for future vaccination and precautions required in the asplenic condition was also lacking. Nine patients had postsplenectomy complications, although there were no cases of OPSI.Conclusions:Adherence to standard guidelines for the management of splenectomised patients was unsatisfactory. There is a need for an improvement of the vaccination rate and careful documentation of this important health risk in the discharge summaries. Maintenance of a splenectomy registry could aid in optimising the management of these patients.
ON JONES' PLANAR ALGEBRAS
Authors: KODIYALAM VIJAY , SUNDER V. S. 
Published: March 2004

We show that a certain natural class of tangles 'generate the collection of all tangles with respect to composition'. This result is motivated by, and describes the reasoning behind, the 'uniqueness assertion' in Jones' theorem on the equivalence between extremal subfactors of finite index and what we call 'subfactor planar algebras' here. This result is also used to identify the manner in which the planar algebras corresponding to M⊂M1 and Nop⊂Mop are obtained from that of N⊂M. Our results also show that 'duality' in the category of extremal subfactors of finite index extends naturally to the category of 'general' planar algebras (not necessarily finite-dimensional or spherical or connected or C*, in the terminology of Jones).