bluuebunny/crossref_metadata_2025_split huggingface dataset:
Selection for c-mycIntegration Sites in Polyclonal T-Cell Lymphomas
Authors: Broussard Dana R. , Mertz Jennifer A. , Lozano M. , Dudley Jaquelin P. 
Published: July 2002

ABSTRACTType B leukemogenic virus (TBLV) is highly related to mouse mammary tumor virus but induces rapidly appearing T-cell lymphomas in mice. Unlike other T-cell tumors induced by retroviruses, only 5 to 10% of TBLV-induced lymphomas have detectable viral integrations near c-mycby Southern blotting, whereas Northern blotting has shown that most tumors have two- to sixfold overexpression of c-mycRNA. In this report, PCR was used to demonstrate that at least 30% of these lymphomas have TBLV insertions near c-myc. Some tumors contained multiple TBLV proviruses in different locations and orientations, suggesting that the tumors are polyclonal. The integrated proviruses near c-mychad different numbers (two to four) of long terminal repeat (LTR) enhancer repeats, although LTRs with three-repeat enhancers dominated the proviral population. Passage of polyclonal tumors in immunocompetent mice and semiquantitative PCR revealed that only cells with particular integrations were selected for growth. In three of six tumors tested, proviruses containing four-repeat enhancers near c-mycwere selected during tumor passage. Since tumor cell selection may be accomplished by overexpression of c-mycRNA due to proximity to the unique TBLV LTR enhancer, we inserted LTRs at various locations within a plasmid containing the entire c-myclocus and cellular flanking sequences. To quantitatively measure effects on transcription, theRenillaluciferase gene was substituted for most of c-mycexon 2, and transient transfections were performed with c-mycreporter constructs in two different T-cell lines. As expected, insertion of a TBLV LTR with three-repeat enhancers in either orientation, 5" and 3", of themycgene elevated reporter activity from 2- to 160-fold, consistent with enhancer function, but four-repeat LTRs had lower levels of expression compared to three-repeat LTRs. Surprisingly, LTR insertions that gave maximal c-mycexpression in transient-transfection assays declined in tumor cells selected for growth in vivo. Selection for clonal growth may occur in tumor cells that have modest c-mycoverexpression after proviral insertion to prevent apoptosis.
The Human Cytomegalovirus UL35 Gene Encodes Two Proteins with Different Functions
Authors: Liu Yingguang , Biegalke Bonita J. 
Published: July 2002

ABSTRACT

The human cytomegalovirus (HCMV) virion is a complex structure that contains at least 30 proteins, many of which have been identified. We determined that the HCMV UL35 gene encodes two proteins, including a previously unidentified virion protein. A 22-kDa phosphoprotein (ppUL35
A
) was translated from a 1.2-kb UL35 transcript by 4 h postinfection; a second phosphoprotein of 75 kDa (ppUL35) was translated from a 2.2-kb transcript predominantly late in infection. The 22-kDa protein localized to the nucleus, while the 75-kDa protein localized to the juxtanuclear compartment and was packaged into virion particles. The 22-kDa protein was identical to the COOH-terminal end of the 75-kDa protein but was not found in virions, thus defining the NH
2
-terminal portion of the 75-kDa protein as essential for packaging. Expression of the 22-kDa protein inhibited activation of the major immediate-early promoter by ppUL82 (pp71), suggesting that the UL35 22-kDa protein may modulate expression of the major immediate-early gene.
Herpes Simplex Virus Selectively Induces Expression of the CC Chemokine RANTES/CCL5 in Macrophages through a Mechanism Dependent on PKR and ICP0
Authors: Melchjorsen Jesper , Pedersen Finn S. , Mogensen Søren C. , Paludan Søren R. 
Published: July 2002

ABSTRACTRecruitment of leukocytes is essential for eventual control of virus infections. Macrophages represent a leukocyte population involved in the first line of defense against many infections, including herpes simplex virus (HSV) infection. Through presentation of antigens to T cells and production of cytokines and chemokines, macrophages also constitute an important link between the innate and adaptive immune systems. Here, we have investigated the chemokine expression profile of macrophages after HSV infection and the virus-cell interactions involved. By reverse transcription-PCR and cDNA arrays, we found that HSV type 1 (HSV-1) and HSV-2 induced expression of the CC chemokine RANTES/CCL5 in murine macrophage cell lines and peritoneal cells. The CXC chemokine BCA-1/CXCL13 was also induced in peritoneal cells. Twenty-six other chemokines tested were not affected. Accumulation of RANTES mRNA was detectable after 5 h of infection, was sensitive to UV irradiation of the virus, and was preceded by accumulation of viral immediate-early mRNA and proteins. The viral components responsible for initiation of RANTES expression were examined with virus mutants and RAW 264.7 macrophage-like cells expressing a dominant negative mutant of the double-stranded-RNA-activated protein kinase (PKR). The PKR mutant cell line displayed reduced constitutive and HSV-inducible RANTES expression compared to the control cell line. HSV-1 mutants deficient in genes encoding the immediate-early proteins ICP4, ICP22, and ICP27 remained fully capable of inducing RANTES expression in macrophages. By contrast, the ability of an ICP0-deficient HSV-1 mutant to induce RANTES expression was compromised. Thus, HSV selectively induces expression of RANTES in macrophages through a mechanism dependent on cellular PKR and viral ICP0.
Capsid Protein C of Tick-Borne Encephalitis Virus Tolerates Large Internal Deletions and Is a Favorable Target for Attenuation of Virulence
Authors: Kofler Regina M. , Heinz Franz X. , Mandl Christian W. 
Published: July 2002

ABSTRACT
Deletions ranging in size from 4 to 21 amino acid residues were introduced into the capsid protein of the flavivirus tick-borne encephalitis (TBE) virus. These deletions incrementally affected a hydrophobic domain which is present at the center of all flavivirus capsid protein sequences and part of which may form an amphipathic alpha-helix. In the context of the full-length TBE genome, the deletions did not measurably affect protein expression and up to a deletion length of 16 amino acid residues, corresponding to almost 17% of mature protein C, viable virus was recovered. This virus was strongly attenuated but highly immunogenic in adult mice, revealing capsid protein C as a new and attractive target for the directed attenuation of flaviviruses. Apparently, the larger deletions interfered with the correct assembly of infectious virus particles, and this disturbance of virion assembly is likely to be the molecular basis of attenuation. However, all of the mutants carrying large deletions produced substantial amounts of subviral particles, which as judged from density gradient analyses were identical to recombinant subviral particles as obtained by the expression of the surface proteins prM and E alone. The structural and functional flexibility of protein C revealed in this study and its predicted largely alpha-helical conformation are reminiscent of capsid proteins of other enveloped viruses, such as alphaviruses (N-terminal domain of the capsid protein), retroviruses, and hepadnaviruses and suggest that all of these may belong to a common structural class, which is fundamentally distinct from the classical β-barrel structures of many icosahedral viral capsids. The possibility of attenuating flaviviruses by disturbing virus assembly and favoring the production of noninfectious but highly immunogenic subviral particles opens up a promising new avenue for the development of live flavivirus vaccines.
Preferential Localization of the Epstein-Barr Virus (EBV) Oncoprotein LMP-1 to Nuclei in Human T Cells: Implications for Its Role in the Development of EBV Genome-Positive T-Cell Lymphomas
Authors: Xu Jingwu , Ahmad Ali , Menezes José 
Published: July 2002

ABSTRACTThe Epstein-Barr virus (EBV)-encoded latent membrane protein-1 (LMP-1) is thought to play a role in the EBV-induced B-cell transformation and immortalization. EBV has also been implicated in certain human T-cell lymphomas; however, the phenotypic effects of the expression of this oncoprotein in T cells are not known. To learn whether LMP-1 also induces phenotypic changes in T cells, we stably expressed it in human cell lines of T and B lineages and 25 LMP-1-expressing T-cell clones and 7 B-cell clones were examined. Our results show for the first time that, in sharp contrast to B cells, LMP-1 preferentially localizes to nuclei in T cells and does not induce the phenotypic changes in these cells that it induces in B cells, does not associate with TRAF proteins, and does not arrest the cell cycle in the G2/M phase. A computer-assisted analysis revealed that LMP-1 lacks the canonical nuclear localization signal. Our results suggest that this oncoprotein may not play the same role in the lymphomagenesis of T cells as it does in B cells.
Induction of Long-Term Memory CD8+T Cells for Recall of Viral Clearing Responses against Influenza Virus
Authors: Deliyannis Georgia , Jackson David C. , Ede Nicholas J. , Zeng Weiguang , Hourdakis Irene , Sakabetis Evaline , Brown Lorena E. 
Published: July 2002

ABSTRACTInduction of cytotoxic T-cell-mediated virus-clearing responses by influenza virus T cell determinant-containing peptide immunogens was examined. The most potent synthetic immunogens for eliciting pulmonary viral-clearing responses contained peptides representing determinants for CD4 and CD8 T cells (TH and CTL peptides, respectively) together with two or four palmitic acid (Pal) groups. Inoculated in adjuvant, these Pal2- or Pal4-CTL-TH lipopeptides and the nonlipidated CTL peptide induced equivalent levels of cytolytic activity in the primary effector phase of the response. The ability to recall lytic responses, however, diminished much more rapidly in CTL peptide-primed than in lipopeptide-primed mice. By 15 months postpriming, the recalled lytic activity in lipopeptide-inoculated mice remained potent, but the response induced by the CTL peptide was weak. Enumeration of specific gamma interferon-secreting CD8 T cells revealed that a greater number of these T cells had entered or remained in the memory pool in lipopeptide-primed mice, arguing for a quantitative rather than qualitative enhancement of the response on recall. Addition of either the lipid or the TH peptide to the CTL peptide was not sufficient to provide these long-lived antiviral responses, but inclusion of both components augmented the response. CD4 T cells elicited by the lipopeptides did not influence the rate of viral clearance upon challenge and most likely had a role in induction or maintenance of the memory response. It therefore appears that the lipopeptide immunogens, although not significantly superior at inducing primary effector CD8 T cells, elicit a much more effective memory population, the recall of which may account for their superiority in inducing pulmonary protection after viral challenge.
Specific Incorporation of Heat Shock Protein 70 Family Members into Primate Lentiviral Virions
Authors: Gurer Cagan , Cimarelli Andrea , Luban Jeremy 
Published: July 2002

ABSTRACT

To determine if any heat shock proteins are incorporated into human immunodeficiency virus type 1 (HIV-1) virions in a manner similar to that of the peptidyl-prolyl isomerase cyclophilin A, we probed purified virions with antibodies against heat shock proteins Hsp27, Hsp40, Hsp60, Hsp70, Hsc70, and Hsp90. Of these proteins, Hsp60, Hsp70, and Hsc70 associated with virions purified based on either particle density or size and were shown to be incorporated within the virion membrane, where they were protected from digestion by exogenous protease. Virion incorporation of Hsp70 was also observed with HIV-2 and with simian immunodeficiency viruses SIV
MAC
and SIV
AGM
, but it appears to be specific for primate lentiviruses, since Hsp70 was not detected in association with Moloney murine leukemia virus virions. Of the HIV-1 genes,
gag
was found to be sufficient for Hsp70 incorporation, though Hsp70 was roughly equimolar with
pol
-encoded proteins in virions.
Behaviour and developmental effects of otitis media with effusion into the teens
Authors: Bennett K E , Haggard M P , Silva P A , Stewart I A 
Published: July 2002

OBJECTIVETo examine whether behavioural or cognitive sequelae of otitis media with effusion (OME) continue into late childhood and the early teens (11–18 years).SETTINGData from a large multipurpose birth cohort study: the Dunedin multidisciplinary health and development study.PARTICIPANTSAround 1000 children from the study. The main independent variable of interest was otological status of the child up to age 9.MAIN OUTCOME MEASURESParent and teacher rated behaviour problems, including antisocial, neurotic, hyperactive, and inattentive behaviours, and tests of academic achievement including intelligence quotient (IQ), reading, and spelling were available in a high proportion of the cohort at ages 11 to 18 years.RESULTSAfter adjustments for covariates such as socioeconomic status, hyperactive and inattentive behaviour problems were evident as late as 15 years, and lower IQ associated with OME remained significant to 13 years. The largest effects were observed for deficits in reading ability between 11 and 18 years.CONCLUSIONSNo previous study considering behaviour problems as an outcome has followed children long enough to determine whether some of the early sequelae of OME are still present in the early to late teens. Some developmental sequelae of OME, particularly deficits in reading ability, can persist into late childhood and the early teens.
Aerobic and anaerobic power responses to the practice of taekwon-do
Authors: Melhim A F 
Published: July 2002

Background—Practising the martial art of taekwon-do (TKD) has been proposed to have beneficial effects on cardiovascular fitness as well as general physical ability. Furthermore, TKD masters and participants have promoted TKD as a total fitness programme. Research studies substantiating this, however, seem to be lacking, perhaps because TKD is recognised more as a method of self defence than a fitness programme.Methods—Nineteen TKD practitioners with an average age of 13.8 years and 10.4 months of TKD training experience were recruited to participate. Measurements included resting heart rate, aerobic power, anaerobic power, and anaerobic capacity.Results—Pairedttest analysis showed no significant differences in either resting heart rate or aerobic power after training. However, significant differences were observed in anaerobic power and anaerobic capacity (p = 0.05). The increases in anaerobic power and anaerobic capacity were 28% and 61.5% respectively.Conclusion—The practice of TKD promotes anaerobic power and anaerobic capacity, but not aerobic power, in male adolescents.
Ultrasound diagnosis and neurodevelopmental outcome of localised and extensive cystic periventricular leucomalacia
Authors: Pierrat V , Duquennoy C , van Haastert I C , Ernst M , Guilley N , de Vries L S 
Published: July 2002

AIMSTo compare the ultrasound (US) evolution and neurodevelopmental outcome of infants with localised (grade II) and extensive (grade III) cystic periventricular leucomalacia (c-PVL).METHODSOver a nine year period, c-PVL was diagnosed in 96/3451 (2.8%) infants in two hospital cohorts. Eighteen were excluded from the study. Thirty nine infants with grade II PVL were compared with 39 infants with grade III PVL.RESULTSThe two populations were comparable for gestational age and birth weight. In infants with grade II PVL, cysts were noted to develop more often after the first month of life (53%) in contrast with grade III PVL (22%) (odds ratio (OR) 3.81 (95% confidence interval (CI) 1.19 to 12.63)). Cysts were also more often unilateral in grade II (54%) than in grade III PVL (0%) (OR indefinite; RR 3.17 (95% CI 2.16 to 4.64)). At 40 weeks postmenstrual age (PMA), cysts were no longer seen on US in 13/38 infants with grade II PVL, with ventriculomegaly being the only visible sequel in nine cases. In grade III PVL, cysts were still present in 25 of the 27 surviving infants. Nine infants with grade II PVL were free of motor sequelae at follow up compared with one infant with grade III PVL (OR 8.07 (95% CI 0.92 to 181.66)). Twenty two out of 29 children with grade II PVL who developed cerebral palsy achieved independent walking compared with 3/26 with grade III PVL (OR 75 (95% CI 11.4 to 662)).CONCLUSIONSIn the cohort studied, 50% of the infants with c-PVL had a more localised form (grade II). In grade II PVL, the cysts developed beyond the first month of life in more than half of the cases and were often no longer visible, on US, at 40 weeks PMA. In order not to miss this diagnosis, sequential US should also be performed beyond the first month of life. Mild ventriculomegaly noted at term can sometimes be due to grade II c-PVL. Cerebral palsy was slightly less common and tended to be less severe in infants with grade II PVL than in those with grade III PVL.
Muscle changes in the neuroleptic malignant syndrome
Authors: Behan W M H , Madigan M , Clark B J , Goldberg J , McLellan D R 
Published: July 2002

Aims—To characterise the skeletal muscle changes in the neuroleptic malignant syndrome (NMS).Methods—Detailed light and ultrastructural examination was carried out on skeletal muscle from three cases of NMS, two associated with recreational drugs (3,4-methlenedioxymethylamphetamine (MDMA, Ecstasy) and lysergic acid diethylamide (LSD)) and one with antipsychotic drugs (fluoxetine (Prozac) and remoxipride hydrochloride monohydrate (Roxiam)).Results—The muscles were grossly swollen and oedematous in all cases, in one with such severe local involvement that the diagnosis of sarcoma was considered. On microscopy, there was conspicuous oedema. In some fascicles less than 10% of fibres were affected whereas in others more than 50% were pale and enlarged. There was a spectrum of changes: tiny to large vacuoles replaced most of the sarcoplasm and were associated with necrosis. A striking feature in some fibres was the presence of contraction bands separating segments of oedematous myofibrils. Severe endomysial oedema was also detectable. There was a scanty mononuclear infiltrate but no evidence of regeneration.Conclusions—The muscle changes associated with NMS are characteristic and may be helpful in differential diagnosis.
Postmortem findings after fatal anaphylactic reactions: Table 1
Authors: Pumphrey Richard S H , Roberts Ian S D 
Published: July 2002

Aims—To determine the frequency at which classic manifestations of anaphylaxis are present at necropsy after fatal anaphylactic reactions.Methods—A register has been established of fatal anaphylactic reactions in the UK since 1992, traced from the certified cause of death and other sources. Details of the previous medical history and the reaction suggest anaphylaxis as the cause of death for 130 cases; a postmortem report was available for 56.Results—The 56 deaths studied included 19 reactions to bee or wasp venom, 16 to foods, and 21 to drugs or contrast media. Death occurred within one hour of anaphylaxis in 39 cases. Macroscopic findings included signs of asthma (mucous plugging and/or hyperinflated lungs) (15 of 56), petechial haemorrhages (10 of 56), pharyngeal/laryngeal oedema (23 of 56), but for 23 of 56 there was nothing indicative of an allergic death. Mast cell tryptase was raised in 14 of 16 cases tested; three of three tested had detectable IgE specific for the suspected allergen.Conclusions—In many cases of fatal anaphylaxis no specific macroscopic findings are present at postmortem examination. This reflects the rapidity and mode of death, which is often the result of shock rather than asphyxia. Investigations that might help determine whether anaphylaxis was the cause of death had rarely been performed. In the presence of a typical clinical history, absence of postmortem findings does not exclude the diagnosis of anaphylaxis.
Western blotting is useful in the salivary diagnosis ofHelicobacter pyloriinfection
Authors: Ballam L D , Mendall M A , Asante M , Morris J , Strachan D P , Whincup P H , Cook D G 
Published: July 2002

Background—The salivary diagnosis ofHelicobacter pyloriinfection offers attractive possibilities for the epidemiological study of infection in children. Salivary enzyme linked immunosorbent assay (ELISA) is less reliable then serum ELISA, owing to variable transudation of immunoglobulin. In addition, children are more difficult to study because of lower specific serum antibody concentrations toH pylori. The performance of salivary western blotting in comparison with serum western blotting and serum ELISA was investigated in school children.Subjects and methods—Paired serum and saliva specimens were obtained from 665 school children aged 9–11 in 10 British towns. All saliva and serum specimens were first analysed by ELISA; subsequently, western blotting of both specimens was performed on 31 and 34 specimens, respectively, to establish the criteria for positivity for western blotting. The remaining 121 specimens were then tested blindly and saliva was compared with the serum.Results—The sensitivity and specificity of salivary ELISA in the 665 specimens was 32 of 50 (64%) and 530 of 691 (87%), respectively, when compared with serum ELISA. The western blotting validation was performed on 28 subjects with positive serum and positive salivary ELISA, 28 saliva positives with negative serum, 16 saliva negatives with positive serum, and 50 doubly negative subjects. Compared with serum western blots, the sensitivity and specificity of salivary western blots was 38 of 47 (81%) and 68 of 75 (91%), respectively. Using serum ELISA as the gold standard, the sensitivity and specificity were 32 of 44 (73%) and 72 of 78 (92%), respectively, the specificity being significantly higher than salivary ELISA (p < 0.001).Conclusion—Salivary western blotting for IgG is useful in the diagnosis ofH pyloriinfection and is superior to ELISA. It also permits the identification of pathogenic strains.