bluuebunny/crossref_metadata_2025_split huggingface dataset:
Longitudinal sero‐reactivity to human herpesvirus 8 (KSHV) in the Swiss HIV Cohort 4.7 years before KS
Authors: Quinlivan E. Byrd , Wang Rui Xue , Stewart Paul W. , Kolmoltri Chulaluk , Regamey Nicolas , Erb Peter , Vernazza Pietro L. ,   the Swiss HIV Cohort Study
Published: August 2002

AbstractThe relationship between viral infection with Kaposi sarcoma‐associated herpesvirus (KSHV) and the onset of Kaposi sarcoma (KS) in AIDS patients is incompletely understood. This study investigates the use of three serological assays to predict the development of KS in HIV‐positive patients. Serially collected serum samples from 36 patients with KS and matched controls in the Swiss HIV Cohort Study (SHCS) were analyzed in a case control study. Three serologic assays to detect antibodies against KSHV (nuclear and membrane antigen immunofluorescence assay, N‐IFA, M‐IFA and ORF 65.2 ELISA) were used to determine the predictive value of KSHV‐seropositivity. Serial samples from the cases were also analyzed to determine longitudinal patterns of seroreactivity and identify cases of seroconversion. Assay sensitivity for detection of KSHV antibodies was highest for M‐IFA (83%), followed by N‐IFA (74%) and 65.2 ELISA (52%). At the time of initial serum sampling (median 4.7 years before KS), only the N‐IFA distinguished case and control sera (61% vs. 32%) and no assay was clearly predictive of subsequent onset of clinical KS. Moreover, an unexpectedly high rate of reversions to seronegativity were observed by N‐IFA (27/33) as well as by 65.2 ELISA (11/26) in the longitudinal analysis. Analysis of the ORF65.2 ELISA index indicated that these reversions before the clinical onset of KS were associated with antibody levels that frequently hovered around the level of detectability. A marked increase in ORF 65.2 antibody titer occurred in a third of the patients at the time of KS diagnosis. Only two seroconversions were documented. KSHV infection within the SHCS is likely to have preceded HIV infection. KSHV infection alone is not highly predictive of KS development in this cohort of HIV‐infected homosexual men as compared with matched controls. Three KSHV serologic assays, though sensitive at the time of clinical KS are inconsistently positive before the development of AIDS‐related KS. J. Med. Virol. 64:157–166, 2001. © 2001 Wiley‐Liss, Inc.
Strategies for reliable diagnosis of hepatitis C infection: The need for a serological confirmatory assay
Authors: Schröter Matthias , Schäfer Peter , Zöllner Bernhard , Polywka Susanne , Laufs Rainer , Feucht Heinz‐Hubert 
Published: August 2002

AbstractThe aim of the study was to examine whether the diagnosis of Hepatitis C (HCV) infection can be obtained reliably without using an immunoblot‐based confirmation assay. 1,708 EIA‐reactive serum samples were examined retrospectively for (i) optical density value in the screening assay, (ii) reactivity in an immunoblot assay, and (iii) result by RT PCR. In 1,394 (81.0%) samples positive results were obtained by both the HCV EIA and the confirmation assay. OD‐values ≥2.2 were observed in 1026 of these samples, but covered the range from 0.4 to 2.1 in the other 368 samples. The combination of HCV EIA reactivity and indeterminate immunoblot assay was observed in 134 (7.8%) serum samples. HCV RNA was detected in 58 cases by PCR. The OD‐values of these 58 samples ranged from 0.4 to >2.2. Especially reactivity against the core recombinant protein was indicative of PCR positivity. The reactivity by the HCV EIA could not be confirmed by immunoblot assay or PCR in 180 (10.5%) sera. These false reactive sera showed OD values by EIA from 0.3 to 2.1. It is concluded that no threshold values can be defined which would allow differentiation between positive, indeterminate, and false reactive result by HCV EIA without producing an inacceptably high number of false negative diagnoses. Not using immunoblot‐based confirmation would result in many additional PCR examinations. Therefore, confirmation of reactive HCV EIA results by a serological confirmatory assay must remain an essential part of the diagnostic procedure. J. Med. Virol. 64:320–324, 2001. © 2001 Wiley‐Liss, Inc.
Mutations in the X region and core promoter are rare and have little impact on response to interferon therapy for chronic hepatitis B
Authors: Hannoun Charles , Horal Peter , Krogsgaard Kim , Lindh Magnus ,   and the INTERPRED Study Group
Published: August 2002

AbstractTherapy for chronic hepatitis B with interferon‐α (IFN) may result in viral clearance and hepatitis B e seroconversion in 30–40% of patients. It is still unclear whether viral genetic variability influences response rates. However, certain core promoter mutations were recently associated with a better response to IFN. In the present study, the entire X region, including the core promoter, of hepatitis B virus (HBV) from 26 HBeAg‐positive patients treated with IFN for 12 weeks, was sequenced. Serum samples pre‐treatment, at end‐of‐treatment, and at follow‐up of 18 sustained and 8 nonsustained responders were analyzed. Most patients were of European origin and had moderate aminotransferase elevation (mean 2.4 × upper limit of normal) and genotype A infection. Before treatment, 16 patients had an X region identical to a consensus sequence of the corresponding genotype; in the remaining 10 patients, a median of 1.5 mutations were found. After treatment, 1–4 new mutations (mean 1.8) had emerged in 5 patients. There was no association between specific mutations, or the number of mutations, and response to IFN. The low frequency of mutations indicates that analysis of this region is of limited clinical value and that emerging mutations in this region are not major determinants of response to treatment with IFN‐α. J. Med. Virol. 66:171–178, 2002. © 2002 Wiley‐Liss, Inc.
Enterovirus infection can induce immune responses that cross‐react with β‐cell autoantigen tyrosine phosphatase IA‐2/IAR
Authors: Härkönen T. , Lankinen H. , Davydova B. , Hovi T. , Roivainen M. 
Published: August 2002

AbstractInsulin‐dependent (type 1) diabetes is characterized by progressive destruction of insulin‐producing β cells probably by autoreactive T lymphocytes. Viral infections, especially those caused by coxsackieviruses, are postulated to play a role in the pathogenesis of the disease in humans. One mechanism by which viral infections could initiate or accelerate diabetogenic processes is “molecular mimicry,” induction of antiviral immune responses cross‐reacting with epitopes in the β‐cell autoantigens. Tyrosine phosphatases (IA‐2, IAR) represent a major target autoantigen in type 1 diabetes. Both humoral and cellular immune responses are directed to the carboxy‐terminal (C‐terminal) part of the protein. This region has a 5‐amino acid sequence identity, followed by five amino acid similarity with the conservative motif in the VP1‐protein of enteroviruses (PALTAVETGA/HT), which is a highly immunogenic B‐ and T‐cell epitope in enterovirus infection‐induced immune responses. This observation prompted us to investigate potential humoral cross‐reactions between immune responses induced by tyrosine phosphatases and enteroviruses. The reactivities of various peptide‐ and virus‐induced rabbit antisera clearly demonstrated that cross‐reactions do exist, and in both directions. Using epitope mapping, we were able to show that several diabetes‐linked epitopes in IA‐2 were also recognized by CBV‐4‐induced antisera. Immunization of female NOD‐mice with formalin‐inactivated purified strain of coxsackievirus B4 (CBV‐4‐E2) induced an immune response that recognized the IA‐2/IAR diabetogenic peptide. The results obtained with human paired sera, collected during enterovirus infection, indicated that enterovirus infection in humans may also occasionally induce a humoral response that cross‐reacts with IA‐2/IAR. J. Med. Virol. 66:340‐350, 2002. © 2002 Wiley‐Liss, Inc.
Evolution of viral quasispecies in four dominant HlA‐A2 restricted T cell epitopes is not a major reason for viral persistence in interferon‐treated patients with chronic hepatitis C
Authors: Pingel Sabine , Weyer Sandra , Galle Peter R. , Löhr Hanns F. 
Published: August 2002

AbstractIn most patients, chronic hepatitis C virus (HCV) infection persists despite antiviral treatment with interferon‐alpha (IFN‐α) and ribavirin. The aim of the study was to determine whether HCV could evade cellular immune responses through mutations within T cell epitopes. Viral sequences flanking four major CTL epitopes within the HCV core and envelope regions were analyzed by PCR amplification, cloning and sequencing in seven HLA‐A2 positive HCV patients before, during and after antiviral therapy. In addition, cytotoxic T lymphocyte precursor (CTLp) frequencies specific to these epitopes were quantitated by ELISPOT. A total of 13 coding mutations were observed among 650 cloned and sequenced PCR products under or post IFN treatment but no clear selection of viral variants. In detail, the diversity of quasispecies in the two core epitopes remained fairly stable over time despite variable CTLp induction in some individuals. The overall mutation rate in the two envelope epitopes was higher but there was no correlation with specific CTLp frequencies. In conclusion, although evolution of the viral quasispecies during and after antiviral therapy was demonstrated, immune evasion by epitope specific mutations seemed to be not common in interferon nonresponders because the viral complexity did not increase. J. Med. Virol. 66:472–480, 2002. © 2002 Wiley‐Liss, Inc.
Case report: Human herpesvirus 7 associated fatal encephalitis in a peripheral blood stem cell transplant recipient
Authors: Chan Paul K.S. , Chik Ki‐Wai , To Ka‐Fai , Li Chi‐Kong , Shing Matthew M.K. , Ng King‐Cheung , Yuen Patrick M.P. , Cheng Augustine F. 
Published: August 2002

AbstractPrevious studies have suggested a neuroinvasive and neuropersistent potential of human herpesvirus 7 (HHV‐7). In this report, a case of fatal encephalitis is described and its association with HHV‐7 infection is discussed. An 8‐year‐old girl received a peripheral blood stem cell transplant for relapsed acute lymphoblastic leukaemia. The post‐transplant period was uneventful and a course of intrathecal chemotherapy was given on Day‐30. On Day‐41, she developed acute encephalopathy with diplopia and nystagmus. She ran a rapid downhill course and succumbed despite antiviral treatment. The only positive pathological finding was the multiple microscopic foci of haemorrhage associated with neuronal degeneration detected in the brain stem. All microbiological investigations were negative, except for the presence of HHV‐7 DNA in cerebrospinal fluid and brain stem tissue samples. J. Med. Virol. 66:493–496, 2002. © 2002 Wiley‐Liss, Inc.
Population‐based type‐specific prevalence of high‐risk human papillomavirus infection in middle‐aged Swedish Women
Authors: Forslund Ola , Antonsson Annika , Edlund Karin , van den Brule Adrian J.C. , Hansson Bengt‐Göran , Meijer Chris. J.L.M. , Ryd Walter , Rylander Eva , Strand Anders , Wadell Göran , Dillner Joakim , Johansson Bo 
Published: August 2002

AbstractHuman papillomavirus (HPV) DNA testing can be used to identify women at risk of the development of cervical cancer. The cost‐effectiveness of HPV screening is dependent on the type‐specific HPV prevalence in the general population. The present study describes the prevalence and spectrum of high‐risk HPV types found in a large real‐life population‐based HPV screening trial undertaken entirely within the cervical screening program offered to middle‐aged Swedish women. Cervical brush samples from 6,123 women aged 32–38 years were analyzed using a general HPV primer (GP5+/6+) polymerase chain reaction‐enzyme immunoassay (PCR‐EIA) combined with reverse dot‐blot hybridization for confirmation and HPV typing by a single assay. In this study, 6.8% (95% CI 6.2–7.5) (417/6,123) were confirmed as high‐risk HPV positive. Infections with 13 different high‐risk HPV types were detected, of which HPV 16 was the most prevalent type (2.1%; 128/6,123), followed by HPV 31 (1.1%; 67/6,123). Any one of the HPV types 18, 33, 35, 39, 45, 51, 52, 56, 58, 59, or 66 was detected in 3.6% (223/6,123) of the women. Infection with two, three, and five types simultaneously was identified in 32, 5, and 1 women, respectively. The combination of PCR‐EIA as a screening test and reverse dot‐blot hybridization as a confirmatory test, was found to be readily applicable to a real‐life population‐based cervical screening. The type‐specific HPV prevalence found support in previous modeling studies suggesting that HPV screening may be a favorable cervical screening strategy. J. Med. Virol. 66:535–541, 2002. © 2002 Wiley‐Liss, Inc.
3‐Ureidopropionate contributes to the neuropathology of 3‐ureidopropionase deficiency and severe propionic aciduria: A hypothesis
Authors: Kölker Stefan , Okun Jürgen G. , Hörster Friederike , Assmann Birgit , Ahlemeyer Barbara , Kohlmüller Dirk , Exner‐Camps Sonja , Mayatepek Ertan , Krieglstein Josef , Hoffmann Georg F. 
Published: August 2002

Abstract3‐Ureidopropionate (3‐UPA) is a physiologic metabolite in pyrimidine degradation. Pathological accumulation of 3‐UPA in body fluids is found in 3‐ureidopropionase deficiency and severe forms of propionic aciduria. Both diseases clinically present with a severe neuropathology involving gray and white matter as well as with a dystonic dyskinetic movement disorder. To date nothing is known about the toxic nature of this metabolite. The aim of the present study was to elucidate whether 3‐UPA may act as endogenous neurotoxin. Exposure of cultured chick neurons to 3‐UPA induced a concentration‐ and time‐dependent neurodegeneration. Neuronal damage was reduced by the antioxidant α‐tocopherol and the N‐methyl‐D‐aspartate (NMDA) receptor antagonist MK‐801. In contrast, the non‐NMDA receptor antagonist CNQX, the metabotropic glutamate receptor antagonist L‐AP3, and succinate showed no protective effect. Furthermore, 3‐UPA elicited an increased production of reactive oxygen species followed by a delayed increase in intracellular calcium concentrations. Activity measurement of single respiratory chain complexes I‐V revealed an inhibition of complex V activity, but not of the electron‐transferring complexes I‐IV by 3‐UPA. In contrast, 3‐UPA did not affect the mitochondrial β‐oxidation of fatty acids. In conclusion, our results provide strong evidence that 3‐UPA acts as endogenous neurotoxin via inhibition of mitochondrial energy metabolism, resulting in the initiation of secondary, energy‐dependent excitotoxic mechanisms. J. Neurosci. Res. 66:666–673, 2001. © 2001 Wiley‐Liss, Inc.
Initiation and development of experimental autoimmune neuritis in Lewis rats is independent of the cytotoxic capacity of NKR‐P1A+ cells
Authors: Yu Shuo , Zhu Yu , Chen Zhiguo , Alheim Mats , Ljungberg Anna , Zhu Jie 
Published: August 2002

AbstractNatural killer (NK) cells are implicated in T cell‐mediated autoimmune diseases. Experimental autoimmune neuritis (EAN) is a CD4+ T cell‐mediated animal model of the Guillain‐Barré syndrome in human. The role of NK cells in the initiation and development of EAN remains unclear. In the present study, we demonstrate that anti‐NKR‐P1A monoclonal antibody (mAb) treatment in vivo did not affect the initiation and development of clinical EAN in Lewis rats induced by immunization with peripheral nerve myelin P0 protein peptide 180–199 and Freund's complete adjuvant, as well as the proportion of NKR‐P1A+ cells (including NK cells and NKT cells) in the spleen. Furthermore, inflammatory cell infiltrations and demyelination in the peripheral nervous system (PNS) and in vitro P0 peptide 180–199‐specific splenocyte proliferation were not different in anti‐NKR‐P1A mAb‐treated rats compared to the control antibody‐treated rats. The cytotoxic activity of NKR‐P1A+ cells, determined by NK cell‐sensitive K562 cells as target cells, decreased markedly in anti‐NKR‐P1A mAb‐treated rats, suggesting that decrease of the cytotoxic activities of NKR‐P1A+ cells is not sufficient to alter clinical EAN, although NKR‐P1A+ cells may participate in the pathogenesis of T cell‐mediated autoimmune diseases, such as EAN, by the mechanisms that involve the release of cytokines. © 2002 Wiley‐Liss, Inc.
Adenosine triphosphate and diadenosine pentaphosphate induce [Ca2+]i increase in rat basal ganglia aminergic terminals
Authors: Giraldez Lisandro , Díaz‐Hernández Miguel , Gómez‐Villafuertes Rosa , Pintor Jesus , Castro Enrique , Miras‐Portugal M. Teresa 
Published: August 2002

AbstractSynaptosomal preparations from rat midbrain exhibit specific responses to both ATP and Ap5A, which stimulate a [Ca2+]i increase in the presynaptic terminals via specific ionotropic receptors, termed P2X, and diadenosine polyphosphate receptors. Aminergic terminals from rat brain basal ganglia were characterized by immunocolocalization of synaptophysin and the vesicular monoamine transporter VMAT2 and represent 29% of the total. These aminergic terminals respond to ATP and/or Ap5A with an increase in the intrasynaptosomal calcium concentration as measured by a microfluorimetric technique. This technique, which allows single synaptic terminals to be studied, showed that roughly 8.2% ± 1.6% of the aminergic terminals respond to ATP, 16.9% ± 1.3% respond to Ap5A, 32.6% ± 0.8% to both, and 42.3% ± 1.5% of them have no response. Immunological studies performed with antibodies against ionotropic ATP receptor subunits showed positive labelling with anti‐P2X3 antibodies in 39% of the terminals. However, colocalization studies of VMAT and P2X3 receptor subunit indicate that only 25% of the aminergic terminals also contain this receptor subtype. These results demonstrate that the aminergic terminals from the rat brain basal ganglia are to a large extent under the modulation of presynaptic nucleotide and dinucleotide receptors. J. Neurosci. Res. 64:174–182, 2001. © 2001 Wiley‐Liss, Inc.
Activated microglia in the human glaucomatous optic nerve head
Authors: Yuan Liya , Neufeld Arthur H. 
Published: August 2002

AbstractTo investigate the distribution and potential participation of microglia, the resident defense cells of the central nervous system, in the optic nerve head (ONH) in glaucoma, histological paraffin sections of optic nerves from normal and glaucoma patients with mild to advanced nerve damage were studied using double labeling immunohistofluorescence. A monoclonal antibody for HLA‐DR, indicating activated microglia, was colocalized with antibodies for functional proteins. In normal ONHs, microglia do not contain TGF‐β2, COX‐2, or TNF‐α and are not positive for PCNA; however, in glaucomatous ONHs, microglia contain abundant TGF‐β2, TNF‐α, and PCNA. In glaucomatous eyes, a few microglia are usually positive for COX‐2. In normal ONHs, there are rarely microglia containing TGF‐β1, NOS‐2, TSP, TIMP‐2, and CD68, but, in glaucomatous tissue, a few microglia are positive from the prelaminar to the postlaminar regions. MMP‐1, MMP‐2, MMP‐3, and MMP‐14 are constitutively present in the perivascular microglia in normal ONHs and appear to be more abundant in glaucomatous tissue. COX‐1, TNF‐R1, TIMP‐1, and c‐fms are constitutively present in normal tissues and appear to be increased in microglia in the glaucomatous ONHs. HSP27 is not present in microglia. In glaucomatous ONHs, microglia become activated and phagocytic and produce cytokines, mediators, and enzymes that can alter the extracellular matrix. Our findings suggest that activated microglia may participate in stabilizing the tissue early in the disease process, but, as the severity of the glaucomatous damage increases, the activities of microglia may have detrimental consequences for the pathological course of glaucomatous optic neuropathy. J. Neurosci. Res. 64:523–532, 2001. © 2001 Wiley‐Liss, Inc.
Histochemical study of acute and chronic intraperitoneal nicotine effects on several glycolytic and Krebs cycle dehydrogenase activities in the frontoparietal cortex and subcortical nuclei of the rat brain
Authors: Turégano L. , Martínez‐Rodríguez R. , Álvarez M.I. , Gragera R.R. , Gómez de Segura A. , De Miguel E. , Toledano A. 
Published: August 2002

AbstractThe effects of nicotine on the activity of different dehydrogenases in frontoparietal regions and subcortical nuclei of the rat brain have been studied using histochemical methods. Nicotine sulphate was intraperitoneally administered in acute (4 mg/kg/day × 3 days) or chronic (ALZET osmotic pump providing 2 mg/kg/day × 15 days) doses. The enzymes analyzed were glyceraldehyde‐3‐phosphate, lactate, malate and succinate dehydrogenases (gly3PDH, LDH, MDH, and SDH, respectively). The results demonstrate that chronic as well as acute administration of nicotine produced strong increases in all these enzymatic activities in the superior layers (I, II and III) of the frontoparietal cortex (cingulate, motor and somatosensory regions); but high increases were not seen in the deeper layers of the cortex or in the subcortical nuclei (substantia nigra, caudate‐putamen, nucleus accumbens or nucleus basalis magnocellularis). These hyperactivities were produced in brain regions with normally low enzymatic activity (cortex), but not in those with great intensity (subcortical nuclei). The results are in rough agreement with previous reports on nicotine‐induced increases in glucose utilization, gly3PDH genic expression and neuronal hyperactivity in the brain cortex; but significant discrepancies between the cortical enzymatic maps and those obtained both in these studies and others on nicotine(N)‐receptor localization have been appreciated. The results support the hypothesis that nicotinic cholinergic drugs can have metabolic, long‐lasting stimulant effects on cortical neurons at specific points (probably layer III pyramidal cells and structures with α7‐N‐receptors) of the cortical circuits that could be of great interest in improving altered cognitive functions that are present in Alzheimer disease, as well as in other less severe mental disturbances. Mitochondrial hyperfunction should also be evaluated as a possible side‐effect (as an oxidative stress inductor) of these kinds of drugs. J. Neurosci. Res. 64:626–635, 2001. © 2001 Wiley‐Liss, Inc.
Disturbed oligodendrocyte development and recovery from hypomyelination in a c‐myc transgenic mouse mutant
Authors: Orian Jacqueline M. , Ahern Alan J. , Ayers Margaret M. , Levine Joel M. , Tapp Luke D. , Reynolds Richard 
Published: August 2002

AbstractThe complexity of interactions underlying the elaboration of myelin has been extensively demonstrated. We provide evidence that signals promoting myelination are not confined to the normal developmental time window for myelination and persist well into adult life. The 2‐50 mutant, described previously, carries a c‐myc transgene regulated by a myelin basic protein promoter. This mutant is characterised by severe hypomyelination and abnormal oligodendrocytes in early life, followed by loss of the phenotype and normal longevity. We show that c‐myc expression in early oligodendrocyte development results in a substantial reduction of cells of this lineage. However, apparent complete recovery, associated with loss of c‐myc expression, axonal survival, and gradual myelin accumulation, is observed by 4 months of age. Thus, stimulation of myelination continues during adult life until normal myelin levels are established. We propose that this mutant may contribute to the characterisation of oligodendrocyte responses to myelinating signals. J. Neurosci. Res. 66:46–58, 2001. © 2001 Wiley‐Liss, Inc.