bluuebunny/crossref_metadata_2025 huggingface dataset:
A low‐cost system for monitoring skin conductance during functional MRI
Authors: Shastri Ananda , Lomarev Mikhail P. , Nelson Stephen J. , George Mark S. , Holzwarth Matthew R. , Bohning Daryl E.
Published: August 2002

We built a low‐cost system for monitoring human skin conductance responses (SCRs) in a clinical magnetic resonance (MR) scanner during functional imaging. The average scanner‐induced conductance noise level was suppressed sufficiently to allow SCR measurements over the full range of SCR amplitudes, and functional image signal‐to‐noise ratio was unaffected by the skin conductance apparatus. The system may be useful for a variety of imaging studies. J. Magn. Reson. Imaging 2001;14:187–193. © 2001 Wiley‐Liss, Inc.
Method for quantitative mapping of dynamic MRI contrast agent uptake in human tumors
Authors: Rijpkema Mark , Kaanders Johannes H.A.M. , Joosten Frank B.M. , van der Kogel Albert J. , Heerschap Arend
Published: August 2002

A method is presented for the acquisition and analysis of dynamic contrast‐enhanced (DCE) MRI data, focused on the characterization of tumors in humans. Gadolinium (Gd) contrast was administered by bolus injection, and its effect was monitored in time by fast T1‐weighted MRI. A simple algorithm was developed for automatic extraction of the arterial input function (AIF) from the DCE‐MRI data. This AIF was used in the pixelwise pharmacokinetic determination of physiological vascular parameters in normal and tumor tissue. Maps were reconstructed to show the spatial distribution of parameter values. To test the reproducibility of the method 11 patients with different types of tumors were measured twice, and the rate of contrast agent uptake in the tumor was calculated. The results show that normalizing the DCE‐MRI data using individual coregistered AIFs, instead of one common AIF for all patients, substantially reduces the variation between successive measurements. It is concluded that the proposed method enables the reproducible assessment of contrast agent uptake rates. J. Magn. Reson. Imaging 2001;14:457–463. © 2001 Wiley‐Liss, Inc.
Hepatitis delta virus genotypes I and III circulate associated with hepatitis B virus genotype F In Venezuela
Authors: Quintero Alberto , Uzcátegui Nathalie , Loureiro Carmen Luisa , Villegas Leopolodo , Illarramendi Ximena , Guevara Maria Eugenia , Ludert Juan Ernesto , Blitz Linda , Liprandi Ferdinando , Pujol Flor Helene
Published: August 2002

The genotypes of hepatitis B (HBV) and delta (HDV) viruses circulating among Venezuelan Amerindian populations, where these viruses are endemic, were determined by sequencing of PCR amplified products from HBsAg positive sera. HDV genotype I (n = 7, 6 from West Amerindians), and III (n = 5, 4 from South Amerindians), were found. Only one HDV genotype I isolate was associated with HBV genotype D, 4 HDV genotype I and 2 HDV genotype III infected individuals were co‐infected with HBV genotype F. The failure to detect the South American HDV genotype III in West Amerindians might be related to the outbreak of fulminant hepatitis with high mortality rate occurred between 1979 and 1982, probably affecting more the Amerindians infected with HDV genotype III. These results suggest the circulation of HDV genotype I among Amerindians, probably introduced through European immigrations, and that this HDV genotype is able to replicate in association with HBV genotype F. J. Med. Virol. 64:356–359, 2001. © 2001 Wiley‐Liss, Inc.
Pseudotypes of vesicular stomatitis virus‐bearing envelope antigens of certain HIV‐1 strains permissively infect human syncytiotrophoblasts cultured in vitro: Implications for in vivo infection of syncytiotrophoblasts by cell‐free HIV‐1
Authors: Bácsi Attila , Ebbesen Peter , Szabó Judit , Beck Zoltán , Andirkó István , Csoma Eszter , Tóth Ferenc D.
Published: August 2002

Intrauterine infection of the fetus is clearly an important mode of vertical transmission of human immunodeficiency virus type 1 (HIV‐1). The syncytiotrophoblast layer of the human placenta must be traversed by HIV‐1 in order to reach underlying cells and fetal capillaries. Although HIV‐1 has been detected in the syncytiotrophoblast layer in situ, there is conflicting evidence regarding infection of syncytiotrophoblast cells with cell‐free virus. The phenotypic mixing between HIV‐1 and vesicular stomatitis virus (VSV) has been exploited to assay the susceptibility of human term syncytiotrophoblast cells to penetration by various strains of HIV‐1. VSV(HIV‐1IIIB) and VSV(HIV‐1Ba‐L) pseudotypes were found to enter syncytiotrophoblast cells. In contrast, VSV pseudotyped with envelope glycoproteins of RF, MN, or Ada‐M strains of HIV‐1 did not infect syncytiotrophoblasts. Plating efficiency of VSV(HIV‐1IIIB) and VSV(HIV‐1Ba‐L) was 10‐fold lower on syncytiotrophoblasts than on T‐cells and macrophages, respectively. Incubation of VSV(HIV‐1IIIB) and VSV(HIV‐1Ba‐L) viruses with appropriate HIV‐1 neutralizing sera before infection strongly inhibited entry of pseudotyped VSV into syncytiotrophoblast cells. These findings demonstrated that infection of syncytiotrophoblasts with VSV(HIV‐1) pseudotypes was mediated by Env from IIIB and Ba‐L strains of HIV‐1. Monoclonal antibodies (MAb) to CD4, CXCR4, CCR5, and CCR3 were tested for their ability to block VSV(HIV‐1) infection of syncytiotrophoblast cells. Neither the anti‐CD4 nor the anti‐CXCR4, anti‐CCR5, and anti‐CCR3 MAb had any inhibitory effect on infection of syncytiotrophoblast cells with VSV(HIV‐1) pseudotypes. Results from this study suggest that cell‐free HIV‐1 can enter syncytiotrophoblasts and the susceptibility of these cells to penetration by the virus is strain dependent. Pseudotype infection merely demonstrates that the first steps in HIV‐1 replication are possible in syncytiotrophoblast cells. J. Med. Virol. 64:387–397, 2001. © 2001 Wiley‐Liss, Inc.
Lack of effect of chemokine receptor CCR2b gene polymorphism (64I) on HIV‐1 plasma RNA viral load and immune activation among HIV‐1 seropositive female workers in Abidjan, Côte d'Ivoire
Authors: Adjé Christiane A. , Bilé Célestin E. , Kestens Luc , Koblavi‐Deme Stéphania , Ghys Peter D. , Maurice Chantal , Kalou‐Badirou Mireille , Kabran N'guessan , Ekpini Réné E. , Roels Thierry H. , Wiktor Stefan Z. , Nkengasong John N.
Published: August 2002

The prevalence of the CCR2b–V64I mutation among human immunodeficiency virus (HIV)‐seropositive and ‐seronegative female workers and the potential effect of heterozygosity of this mutation on HIV‐1 plasma RNA viral load and markers of immune activation were assessed. CCR2b–V64I was detected by polymerase chain reaction, followed by restriction enzymes analysis; plasma viral load was measured by the Amplicor HIV‐1 monitor assay and CD4+ T‐cell counts and markers of immune activation by standard three‐color FACscan flow cytometry. Of the 260 female workers, 56 (21.5%) were heterozygous for CCR2b–V64I, and 8 (3%) were homozygous. Of the 99 HIV‐seronegative female workers, 19 (19.2%) were heterozygous for the CCR2b–V64I mutation compared with 37 (23%) of the 161 HIV‐seropositive FSW (P = 0.47). In a univariate analysis of viral load among HIV‐seropositive FSW, no difference was noted between those heterozygous for or without the mutation; both groups had plasma viral loads of 5.0 log10 copies/ml. After controlling for the effects of CD4+ T‐cell counts in a multivariate analysis, no significant difference was observed between the groups in viral load or in markers of immune activation. The data suggest that the presence of the CCR2b mutation has no effect on HIV‐1 plasma viral load and markers of immune activation in our study population. The finding that the frequency of this mutation is similar in HIV‐seropositive and ‐seronegative female workers suggests that its presence is not associated with increased risk of HIV infection. J. Med. Virol. 64:398–401, 2001. © 2001 Wiley‐Liss, Inc.
Evolution of the E2 region of hepatitis C virus in an infant infected by mother‐to‐infant transmission
Authors: Sitia Giovanni , Cella Davide , De Mitri Maria Stella , Novati Roberto , Foppa Caterina Uberti , Perackis Katarina , Bianchi Cesare , Lazzarin Adriano , Morsica Giulia
Published: August 2002

To demonstrate vertical transmission of hepatitis C virus from an HCV infected woman and to assess the evolution of HCV quasispecies in the infant, the variable E2 region was analyzed in one mother‐infant pair at birth and in serial samples from the infected baby. Sequence analysis of the E2 region obtained by means of direct sequencing of PCR products of mother‐infant pair at birth, showed that the sequence of the dominant strain in the infant was related closely but not identical to that of her mother. The HCV population in mother‐infant pair at birth and in serial samples of the infant was analyzed by polymerase‐chain reaction‐mediated Single Strand Conformational Polymorphism analysis (SSCP), which can distinguish DNA fragments of the same size as different electrophoretic migration of single stranded DNA. Single Strand Polymorphism analysis revealed that the infant was infected with two mutant genomes whereas the mother had a unique variant. The prevalent strain detected in the baby was not dominant in the mother at delivery and the pattern of quasispecies in the infant at birth was not the same as her mother, suggesting that the infant acquired the infection in utero. Changes in the dominant strain and evolution of the pattern of quasispecies in the infant from the 10th month of age were possibly due to the immune selection of escape mutants. J. Med. Virol. 64:476–481, 2001. © 2001 Wiley‐Liss, Inc.
Prevalence and age distribution of human herpesvirus‐8 specific antibodies in hungarian blood donors
Authors: Juhász Attila , Remenyik Éva , Kónya József , Veress György , Bégány Ágnes , Andirkó István , Medgyessy Ildikó , Hunyadi János , Gergely Lajos
Published: August 2002

Sera of blood donors were investigated by a peptide ELISA and indirect immunofluorescence assay to assess the prevalence of HHV‐8 infection in the Hungarian population. A 14 amino acid long synthetic oligopeptide from the carboxyterminus of orf65/small virus capsid antigen was used as antigen in the ELISA. ELISA results were confirmed by recombinant orf65 antigen Western blot. Antibodies to the latent nuclear antigen were detected by the immunofluorescence assay. Nine of 12 sera obtained from patients with classical Kaposi sarcoma were reactive by ELISA whereas all were positive by immunofluorescence. Four of 482 (0.83%) healthy blood donors had anti‐orf65 peptide antibodies and 17/1089 (1.56%) had antibodies to the latent nuclear antigen. In a group of children ages 1–14 years, antibodies to the latent nuclear antigen (0/29) were not detected. The prevalence of antibodies to the latent nuclear antigen showed a moderate but significant increase in correlation with senescence. In the Kaposi sarcoma patients, the titre of antibodies to the latent nuclear antigen was significantly higher than in the healthy seropositive donors. The overall HHV‐8 seroprevalence by the two assays was 2.28% (11/482) in the Hungarian blood donor group. J. Med. Virol. 64:526–530, 2001. © 2001 Wiley‐Liss, Inc.
MIP‐1α and MIP‐1β induction by dengue virus
Authors: Spain‐Santana Tammy A. , Marglin Stephanie , Ennis Francis A. , Rothman Alan L.
Published: August 2002

Dengue virus (DV) infection can result in either a mild febrile illness known as dengue fever (DF) or a life‐threatening disease called dengue hemorrhagic fever (DHF). DHF is more prevalent in patients undergoing secondary DV infection. This observation has led to the hypothesis that DHF may be the result of immune reactions to the secondary DV infection; an event termed immunopathology. Two cellular factors, MIP‐1α and MIP‐1β, have been found to be induced by infection with DV. MIP‐1 induction by DV infection was observed in a myelomonocytic cell line, as well as in peripheral blood mononuclear cells isolated from a dengue naive donor. MIP‐1 induction was not due to factors secreted by infected cells. In fact, replication‐competent virus was required to induce MIP‐1. Evidence is also provided that MIP‐1 genes are expressed in patients with dengue disease. It is hypothesized that these chemokines may have roles in the immunopathology of dengue infections and may contribute to fever and bone marrow suppression observed in patients with DV infections. J. Med. Virol. 65:324–330, 2001. © 2001 Wiley‐Liss, Inc.
Mixed cryoglobulinaemia and chronic hepatitis C virus infection: The rheumatic manifestations
Authors: Leone N. , Pellicano R. , Maiocco I. Ariata , Modena V. , Marietti G. , Rizzetto M. , Ponzetto A.
Published: August 2002

The prevalence of rheumatologic symptoms in patients with mixed cryoglobulinaemia associated to chronic hepatitis C virus (HCV) infection was investigated. One hundred fourteen patients (96 female, mean age 63.5 years) with chronic HCV infection and cryoglobulinaemia were recruited. The presence, concentration, and type of cryoglobulins were tested by immunofixation. Rheumatoid factor (RF) and antinuclear antibody (ANA) were also measured. Rheumatological related symptoms were investigated by anamnesis and clinical evaluation. HCV genotype was determined by polymerase chain reaction (PCR) with genotype specific primer. Type II cryoglobulinaemia was identified in 39 cases and it was of type III in 58. HCV‐RNA genotype was determined in 62 patients: 47 (76%) were infected by genotype1b, 8 (13%) by genotype 2a, while other genotypes were less common. RF and ANA were, respectively, present in 36 (31.5 %) and 4 (3.5 %) patients at low titre (RF < 50 UI/ml, ANA < 1:80). Of the 114 patients, 51 (44.7%) complained for rheumatological symptoms. The mean cryocrit value in these patients was 2,6 %, while in patients with HCV infection, liver disease, and cryoglobulinaemia without rheumatological symptoms the cryocrit value was lower than 0.5% in 50% of cases. It is concluded that patients with chronic HCV infection reported a wide variety of rheumatological manifestations, impairing their quality of life, with discrete frequency. These results suggest that HCV infection should be considered in the differential diagnosis of rheumatological symptoms of unknown origin. J. Med. Virol. 66:200–203, 2002. © 2002 Wiley‐Liss, Inc.
Hepatitis E virus infection in haemodialysis patients: A case‐control study in Saudi Arabia
Authors: Ayoola E.A. , Want M.A. , Gadour M.O.E.H. , Al‐Hazmi M.H. , Hamza M.K.M.
Published: August 2002

To determine the prevalence of antibody to hepatitis E virus (IgM anti‐HEV) among haemodialysis patients and evaluate whether there was an increased risk of infection and exposure to HEV in an area of endemic viral hepatitis, serum samples obtained from 83 Saudi patients on chronic haemodialysis (group 1), 400 sex‐ and age‐matched healthy subjects (group 2) and hospital patients (group 3) were tested for the IgM anti‐HEV and IgG anti‐HEV. The prevalence of anti‐HEV among the patients (group 1) and the healthy controls were 4.8% and 0.3%, respectively. The difference (4.5%) was statistically significant, with a calculated odds ratio (OR) of 20.2 (95% CI = 2.1–481.0; P = 0.0002). In contrast, there was no significant difference in the prevalence rates of IgG anti‐HEV (7.2% vs 10.8%) in both groups. In nonhaemodialysis patients with various diseases, 1.6% (1 of 64) of outpatients (group 3) and none (0 of 113) of the ward patients (group 4) was positive for IgM anti‐HEV. Thus, the prevalence (4 of 83) of IgM anti‐HEV in the haemodialysis patients was significantly higher than the rate (1 of 177) in the combined groups of nonhaemodialysis hospital patients. The calculated OR was 8.9 (95% CI = 0.92, 212.8; P = 0.037). IgM antibody to hepatitis A virus (IgM anti‐HAV) was not detected in any subjects, and the prevalence rates of IgG anti‐HAV were similar in the patients and controls (72.3% and 74.3% in groups 1 and 2, respectively, and 75.7% combined groups 3 and 4). The study indicated a significantly higher risk of acute HEV infection among patients on chronic haemodialysis. It is possible that these were nosocomial infections acquired by person‐to‐person transmission in the haemodialysis unit. However, it is more probable that the infections were community acquired, a conclusion supported albeit indirectly by the lack of a significant difference between the prevalence in haemodialysis patients (4.8%) and outpatients (1.6%). In areas of endemic HEV, appropriate strategies should be adopted to prevent the risk of HEV among haemodialysis patients. J. Med. Virol. 66:329‐334, 2002. © 2002 Wiley‐Liss, Inc.
Spread of hepatitis E virus among different‐aged pigs: two‐year survey in Taiwan
Authors: Wu Jaw‐Ching , Chen Chuan‐Mu , Chiang Tzen‐Yuh , Tsai Wen‐Hsuan , Jeng Wen‐Juei , Sheen I‐Jane , Lin Chen‐Chun , Meng Xiang‐Jin
Published: August 2002

Swine are reservoirs of hepatitis E virus (HEV). In this study, a 2‐year survey of HEV in feces and sera of swine was conducted to determine if: 1) HEV has circulated among pigs for some time in Taiwan; 2) the spread of HEV among different‐aged pigs; and 3) there exists HEV strains possibly imported through trading. From 1998–2000, 521 serum samples and 54 fecal specimens from pigs were examined by reverse transcription polymerase chain reaction. None of the 11 pigs in suckling stage (< 2 months) were serum HEV RNA positive. The highest viremia rate (4.5%) was in pigs of 2 months age, followed by 1.2% and 1.8% in pigs of growing (3–4 months) and finishing stages (5–6 months), and none in pigs older than 6 months. Viremia showed little variation in different years and areas. None of the 20 fecal samples from pigs in suckling stage were HEV RNA positive, whereas 9% of the 34 samples from pigs in growing or finishing stages were positive. Most swine HEV isolates in Taiwan clustered within the genotype 4, whereas the three HEV isolates cloned from pigs imported recently from the U.S. belonged to the genotype 3 HEV in the U.S. The results suggest that HEV may infect pigs at an early growing stage and spread unnoticed among pigs and possibly across countries through trading. J. Med. Virol. 66:488–492, 2002. © 2002 Wiley‐Liss, Inc.
Enterovirus meningitis in adults in 1999–2000 and evaluation of clinical management
Authors: Peigue‐Lafeuille Hélène , Croquez Nicolas , Laurichesse Henri , Clavelou Pierre , Aumaître Olivier , Schmidt Jeannot , Maillet‐Vioud Marcel , Henquell Cécile , Archimbaud Christine , Bailly Jean‐Luc , Chambon Martine
Published: August 2002

Enterovirus meningitis is well documented in children. However, there is a paucity of reports in adults, despite the availability of genome detection (RT‐PCR) in cerebrospinal fluid (CSF), which provides a rapid and reliable diagnosis. The clinical course and management of 30 cases of entero‐virus proven meningitis prospectively diagnosed between August 1999 and November 2000 in immunocompetent adults were analysed, and laboratory and clinical strategies evaluated. Patient age ranged between 17 and 43 (median 29). The analysis of clinical, biological, and epidemiological data showed the difficulty of recognising enterovirus meningitis in adults. Characteristic symptoms were either inconstant (the association of fever/headache/stiff neck) or misleading (the presence of vesicular lesions). CSF data showed moderate pleocytosis but a predominance of lymphocytes in only 12/27 (44%) patients. An epidemiological background was present in 10/30 (33%) patients, but 10/30 (33%) patients were admitted during cold months. Consequently, although the detection of enterovirus genome in CSF was positive in all cases, the results were communicated within a median of 6 days [2–9] after admission, mainly because the aetiology was not considered early enough. Management of patients varied between departments and between individual physicians, with measures ranging from computed tomography (33%) to the prescription of aciclovir (20%) or antibiotics (53%). Enterovirus meningitis should not be underestimated in adults. Management could be improved and standardised, and costs reduced by more systematic year‐round use of enterovirus RT‐PCR in meningitis, provided results are rapid. J. Med. Virol. 67:47–53, 2002. © 2002 Wiley‐Liss, Inc.
Hemorrhagic fever occurs after intravenous, but not after intragastric, inoculation of rhesus macaques with lymphocytic choriomeningitis virus
Authors: Lukashevich Igor S. , Djavani Mahmoud , Rodas Juan D. , Zapata Juan C. , Usborne Amy , Emerson Carol , Mitchen Jacque , Jahrling Peter B. , Salvato Maria S.
Published: August 2002

Arenaviruses can cause hemorrhagic fever and death in primates and guinea pigs, but these viruses are not highly pathogenic for most rodent carriers. In the United States, arenaviruses precipitated outbreaks of hepatitis in captive monkeys, and they present an emerging health threat in the tropical areas of Africa and South America. We describe infection of rhesus macaques with the prototype arenavirus, lymphocytic choriomeningitis virus (LCMV), using the WE strain that has been known to cause both encephalopathy and multifocal hemorrhage. Five macaques were inoculated: two by the intravenous (i.v.) and three by the intragastric (i.g.) route. Whereas the two i.v.‐inoculated monkeys developed signs and lesions consistent with fatal hemorrhagic fever, the i.g.‐inoculated monkeys had an attenuated infection with no disease. Pathological signs of the primate i.v. infection differ significantly from guinea pig arenavirus infections and make this a superior model for human viral hemorrhagic disease. J. Med. Virol. 67:171–186, 2002. © 2002 Wiley‐Liss, Inc.
Identification of inactive ecto‐5′‐nucleotidase in normal mouse muscle and its increased activity in dystrophic Lama2dy mice
Authors: García‐Ayllón M. Salud , Campoy F. Javier , Vidal Cecilio J. , Muñoz‐Delgado Encarnación
Published: August 2002

Ecto‐5′‐nucleotidase (eNT) activity and protein in normal (NM) and merosin‐deficient dystrophic (DM) Lama2dy mice muscle were studied. eNT activity in DM was three‐ to four‐fold that in NM. eNT in NM and DM displayed the same kinetic properties. Slot and Western blotting revealed that the immunoreactive protein was two to three times more abundant in control muscle, when NM and DM samples with the same eNT activity were compared, indicating that mouse muscle contains catalytically inactive eNT components. eNT activity and protein peaks coincided in sedimentation analyses, revealing that inactive eNT occurs as dimers. Most eNT activity and protein of NM bound to Lens culinaris (LCA) or Ricinus communis (RCA) agglutinins, but half of the activity and one‐third of the protein bound to wheat germ agglutinin (WGA). Although WGA interaction did not permit full separation of inactive eNT, the results suggest that similar proportions of active species with and without WGA reactivity occur in mouse muscle, whereas a great fraction of the inactive eNT variants lack WGA reactivity. Because the level of eNT protein was little modified in DM, the higher eNT activity in dystrophic than in control muscle may result from misregulation in the synthesis of active and inactive eNT species or from conversion of inactive into active components. J. Neurosci. Res. 66:656–665, 2001. © 2001 Wiley‐Liss, Inc.
Zaprinast, an inhibitor of cGMP‐selective phosphodiesterases, enhances the secretion of TNF‐α and IL‐1β and the expression of iNOS and MHC class II molecules in rat microglial cells
Authors: Choi Sang‐Hyun , Choi Dong‐Hee , Song Kwang‐Seon , Shin Kyung‐Ho , Chun Boe‐Gwun
Published: August 2002

Proinflammatory cytokines produced by activated glial cells may in turn augment the immune/inflammatory reactions of glial cells through autocrine and paracrine routes. The NO/cGMP signaling represents one of the reactions of activated glial cells. We investigated whether the production of proinflammatory cytokines by glial cells is affected by NO‐dependent downstream cGMP signaling. In primary cultures of mixed astrocytes and microglial cells, zaprinast (0.1 mM), an inhibitor of cGMP‐selective phosphodiesterases, enhanced the basal and LPS (1.0 μg/ml)‐induced secretion of TNF‐α and IL‐1β. Zaprinast also enhanced NO production induced by LPS or IFN‐γ (100 U/ml), and in microglial cell cultures, but not in astrocyte cultures, zaprinast enhanced the basal and the IFN‐γ‐induced production of the cytokines, TNF‐α and IL‐1β, and of NO. This upregulation by zaprinast was partially inhibited by KT5823 (1.0 μM), an inhibitor of protein kinase G. The LPS‐induced production of TNF‐α, IL‐1β, and NO was inhibited by ODQ (50 μM), an inhibitor of soluble guanylyl cyclase, and by KT5823. Immunohistochemical analysis of mixed glial cell cultures showed that LPS/IFN‐γ‐induced iNOS expression and the enhanced expression of iNOS by zaprinast were restricted to microglial cells. Zaprinast enhanced the IFN‐γ (200 U/ml)‐induced expression of MHC Class II molecules in astrocytes and microglial cells in mixed cultures, but did not enhance this IFN‐γ‐induced expression in pure astrocytes, which lacked paracrine TNF‐α from microglial cells. Summarizing, zaprinast, which is associated with cGMP/protein kinase G signaling, may augment central immune/inflammatory reactions, possibly via the increased production of TNF‐α and IL‐1β by activated microglial cells. © 2002 Wiley‐Liss, Inc.
Cytoskeleton participation in subcellular trafficking of signal transduction proteins in rod photoreceptor cells
Authors: McGinnis James F. , Matsumoto Brian , Whelan James P. , Cao Wei
Published: August 2002

Light sensitivity and adaptation, general characteristics of rod photoreceptor cell vision, allow rods to modulate their response depending on the lighting environment to which they are exposed. In dim light, rods are maximally sensitive, whereas, in bright light, rods are essentially inactive. In the retinas of dark‐adapted mice, arrestin (an inhibitory protein) is located in the rod inner segment (RIS), and transducin (an activating protein) is located in the rod outer segment (ROS). In light‐adapted retinas, the proteins have reciprocal localizations. In this study, our data demonstrate that the temporal and spatial changes in the subcellular localization of arrestin and β‐transducin are correlated with the amount of light to which the animals are exposed. By using the frog Xenopus laevis and immunofluorescence confocal microscopy, our results also show that in the dark‐adapted retina some arrestin remains in the ROS. The data most dramatically demonstrate that this residual arrestin is highly concentrated in the connecting cilium, the axoneme, and the microtubules associated with the disc incisures. These data suggest a structure–function relationship between the light‐dependent positional status of arrestin and the elements of the rod photoreceptor cytoskeleton. The massive, rapid, light‐induced reciprocal changes in the subcellular concentrations of these proteins must directly affect phototransduction and appear to be a general phenomenon by which photoreceptor cells rapidly and transiently regulate the trafficking and subcellular concentration of a variety of signal transduction proteins within the RIS and ROS. Hereditary mutations in the components of the movement mechanism should lead to defects in vision and possibly blindness. © 2002 Wiley‐Liss, Inc.
Down‐regulation of γ‐glutamylcysteine synthetase regulatory subunit gene expression in rat brain tissue during aging
Authors: Liu Rui‐Ming
Published: August 2002

The mechanism underlying age‐related neurodegenerative diseases is still an area of significant controversy. Increased evidence suggests that oxidative stress contributes importantly to neuronal damage observed in the brains of aged animals and in neurodegenerative diseases. Glutathione (GSH), the most abundant intracellular nonprotein thiol, plays an important role in antioxidant defense. The concentration of this important antioxidant decreases with age in the brain, which is accompanied by an increase in oxidative damage to macromolecules. The mechanism underlying the age‐associated decline in GSH content in the brain, however, is not clear. In this study, we demonstrate for the first time that the expression of the regulatory subunit of γ‐glutamylcysteine synthetase (GCS), the rate‐limiting enzyme in de novo GSH synthesis, decreases with age in cerebellum, cerebral cortex, and hippocampus of Fisher 344 rats. This was accompanied by a decline in GCS activity and GSH content. There were no significant differences in either the concentrations of cysteine and glutathione disulfide (GSSG) or the activities of glutathione synthetase (GS), γ‐glutamyl traspeptidase (GGT), and glutathione reductase (GR) in the brains from different age groups. Our results suggest that the age‐associated decrease in GSH in the brain may result from the down‐regulation of GCS regulatory subunit and consequently a decrease in the activity of GCS. © 2002 Wiley‐Liss, Inc.
Dual role for p75NTR signaling in survival and cell death: Can intracellular mediators provide an explanation?
Authors: Mamidipudi Vidya , Wooten Marie W.
Published: August 2002

Several recent reports support a dual role of p75NTR in cell death, as well as survival, depending on the physiological or developmental stage of the cells. Coexpression of the TrkA receptor with p75NTR further enhances the complexity of nerve growth factor (NGF) signaling. Recent identification of serine/threonine kinases that interact with the p75NTR provides an explanation for the lack of an apparent kinase domain needed for signaling. In this report, we review the possible roles of the intracellular proteins that directly interact with the p75NTR, atypical protein kinase C (PKC) binding protein, p62 and second messengers in the functional antagonism exhibited by TrkA and p75NTR with an emphasis on the nuclear factor‐kappa B activation pathway. © 2002 Wiley‐Liss, Inc.
Neurite growth promotion by nerve growth factor and insulin‐like growth factor‐1 in cultured adult sensory neurons: Role of phosphoinositide 3‐kinase and mitogen activated protein kinase
Authors: Kimpinski Kurt , Mearow Karen
Published: August 2002

Although neurons of the PNS no longer require neurotrophins such as Nerve Growth Factor (NGF) for their survival, such factors are involved in regulating axonal sprouting and regeneration after injury. In addition to the neurotrophin receptors, sensory neurons are reported to express IGF‐1, EGF and FGF receptors. To investigate the influence of growth factors in addition to NGF, we examined the effects of IGF‐1 EGF and FGF on neurite growth from adult rat dorsal root ganglion sensory neurons in both dissociated cultures and in compartmented cultures. As expected, NGF elicited robust neuritic growth in both the dissociated and compartmented cultures. The growth response to IGF‐1 was similar, although there was minimal neurite growth in response to EGF or FGF. In addition, IGF‐1 (but neither FGF nor EGF), when applied to cell bodies in compartmented cultures, potentiated the distal neurite growth into NGF‐containing side compartments. This potentiation was not seen when these factors were provided along with NGF in the side compartments of compartmented cultures, or in the dissociated cultures. To determine the contribution of signaling intermediates downstream of receptor activation, we used inhibitors of the potential effectors and Western blotting. The PI 3‐kinase inhibitor, LY294002 attenuated neurite growth evoked by NGF, IGF and EGF in dissociated cultures, although the MAP kinase kinase (MEK) inhibitor PD098059 diminished the growth in only IGF. Immunoprecipitation and Western blotting results demonstrated differential activation of MAPK, PI 3‐kinase, PLCγ1 and SNT by the different factors. Activation of PI 3‐kinase and SNT by both NGF and IGF‐1 correlated with their effects on neurite growth. These results support the hypothesis that the PI 3‐kinase pathway plays an important role in neuritogenesis. J. Neurosci. Res. 63:486–499, 2001. © 2001 Wiley‐Liss, Inc.
TNF‐α stimulates caspase‐3 activation and apoptotic cell death in primary septo‐hippocampal cultures
Authors: Zhao Xiurong , Bausano Brian , Pike Brian R. , Newcomb‐Fernandez Jennifer K. , Wang Kevin K.W. , Shohami Esther , Ringger N.C. , DeFord S.M. , Anderson Douglas K. , Hayes Ronald L.
Published: August 2002

Primary septo‐hippocampal cell cultures were incubated in varying concentrations of tumor necrosis factor (TNF‐α; 0.3–500 ng/ml) to examine proteolysis of the cytoskeletal protein α‐spectrin (240 kDa) to a signature 145 kDa fragment by calpain and to the apoptotic‐linked 120‐kDa fragment by caspase‐3. The effects of TNF‐α incubation on morphology and cell viability were assayed by fluorescein diacetate‐propidium iodide (FDA‐PI) staining, assays of lactate dehydrogenase (LDH) release, nuclear chromatin alterations (Hoechst 33258), and internucleosomal DNA fragmentation. Incubation with varying concentrations of TNF‐α produced rapid increases in LDH release and nuclear PI uptake that were sustained over 48 hr. Incubation with 30 ng/ml TNF‐α yielded maximal, 3‐fold, increase in LDH release and was associated with caspase‐specific 120‐kDa fragment but not calpain‐specific 145‐kDa fragment as early as 3.5 hr after injury. Incubation with the pan‐caspase inhibitor, carbobenzosy‐ Asp‐CH2‐OC (O)‐2‐6‐dichlorobenzene (Z‐D‐DCB, 50‐140 μM) significantly reduced LDH release produced by TNF‐α. Apoptotic‐associated oligonucleosomal‐sized DNA fragmentation on agarose gels was detected from 6 to 72 hr after exposure to TNF‐α. Histochemical changes included chromatin condensation, nuclear fragmentation, and formation of apoptotic bodies. Results of this study suggest TNF‐α may induce caspase‐3 activation but not calpain activation in septo‐hippocampal cultures and that this activation of caspase‐3 at least partially contributes to TNF‐α‐induced apoptosis. J. Neurosci. Res. 64:121–131, 2001. © 2001 Wiley‐Liss, Inc.
Local synthesis of nuclear‐encoded mitochondrial proteins in the presynaptic nerve terminal
Authors: Gioio Anthony E. , Eyman Maria , Zhang Hengshan , Lavina Zeno Scotto , Giuditta Antonio , Kaplan Barry B.
Published: August 2002

One of the central tenets in neuroscience has been that the protein constituents of distal compartments of the neuron (e.g., the axon and nerve terminal) are synthesized in the nerve cell body and are subsequently transported to their ultimate sites of function. In contrast to this postulate, we have established previously that a heterogeneous population of mRNAs and biologically active polyribosomes exist in the giant axon and presynaptic nerve terminals of the photoreceptor neurons in squid. We report that these mRNA populations contain mRNAs for nuclear‐encoded mitochondrial proteins to include: cytochrome oxidase subunit 17, propionyl‐CoA carboxylase (EC 6.4.1.3), dihydrolipoamide dehydrogenase (EC 1.8.1.4), and coenzyme Q subunit 7. The mRNA for heat shock protein 70, a chaperone protein known to be involved in the import of proteins into mitochondria, has also been identified. Electrophoretic gel analysis of newly synthesized proteins in the synaptosomal fraction isolated from the squid optic lobe revealed that the large presynaptic terminals of the photoreceptor neuron contain a cytoplasmic protein synthetic system. Importantly, a significant amount of the cycloheximide resistant proteins locally synthesized in the terminal becomes associated with mitochondria. PCR analysis of RNA from synaptosomal polysomes establishes that COX17 and CoQ7 mRNAs are being actively translated. Taken together, these findings indicate that proteins required for the maintenance of mitochondrial function are synthesized locally in the presynaptic nerve terminal, and call attention to the intimacy of the relationship between the terminal and its energy generating system. J. Neurosci. Res. 64:447–453, 2001. Published 2001 Wiley‐Liss, Inc.
Delayed induction of αB‐crystallin in activated glia cells of hippocampus in kainic acid‐treated mouse brain
Authors: Che Yongzhe , Piao Chun Shu , Han Pyung‐Lim , Lee Ja‐Kyeong
Published: August 2002

Small heat shock proteins have been implicated in playing a role in various cellular processes, including stress‐induced cell death. In kainic acid (KA)‐treated rat brain, the immunoreactivity of heat‐shock protein 27 (HSP27) was markedly increased in glia cells of the limbic system. In the present study, we demonstrated that αB‐crystallin, a member of the small heat‐shock protein family, was strongly induced in reactive astrocytes in hippocampus after KA‐induced seizure. The induction was localized mainly in the CA3 region of hippocampus, where massive neuronal loss occurred. We also demonstrated that the delayed induction of αB‐crystallin and HSP27 immunoreactivities in the hippocampus of epileptic animals was repressed to the levels seen in control animals with preadministration of the selective nNOS inhibitor 7‐nitroindazole (7‐NI). This repression was reversed by coinjection of L‐arginine, a substrate of NOS. Together, these data suggest a role for αB‐crystallin and HSP27 in reactive gliosis and/or in delayed neuronal death proceeded after KA‐induced seizure. J. Neurosci. Res. 65:425–431, 2001. © 2001 Wiley‐Liss, Inc.
Time course studies on the effectiveness of tetrodotoxin in reducing consequences of spinal cord contusion
Authors: Rosenberg Lisa J. , Wrathall Jean R.
Published: August 2002

Focal injection of the sodium channel blocker tetrodotoxin (TTX) into the injury site at either 5 or 15 min after a standardized thoracic contusion spinal cord injury (SCI) reduces white matter pathology and loss of axons in the first 24 hr after injury. Focal injection of TTX at 15 min after SCI also reduces chronic white matter loss and hindlimb functional deficits. We have now tested the hypothesis that the reduction in chronic deficits with TTX treatment is associated with long‐term preservation of axons after SCI and compared both acute (24 hr) and chronic (6 weeks) effects of TTX administered at 15 min prior to and 5 min or 4 hr after SCI. Our results indicate a significant reduction of acute white matter pathology in rats treated with TTX at 15 min before and 5 min after injury but no effect when treatment was delayed until 4 hr after contusion. Compared with injury controls, groups treated with TTX at 5 min and 4 hr after injury did not show a significant deficit reduction, nor was there a significant sparing of white matter at 6 weeks compared with injury controls. In contrast, the group treated with TTX at 15 min before SCI demonstrated significantly reduced hindlimb functional deficits beginning at 1 week after injury and throughout the 6 weeks of the study. This was associated with a significantly higher axon density in the ventromedial white matter at 6 weeks. The results demonstrate that blockade of sodium channels preserves axons from loss after SCI and points to the importance of time of administration of such drugs for therapeutic effectiveness. J. Neurosci. Res. 66:191–202, 2001. © 2001 Wiley‐Liss, Inc.
Sunshine records from Ireland: cloud factors and possible links to solar activity and cosmic rays
Authors: Pallé E. , Butler C.J.
Published: August 2002

The records of sunshine hours obtained since the late 19th century from four stations distributed throughout Ireland were analysed. A gradual decrease in sunshine hours has occurred at all four sites since records began. Increasing cloud factors, resulting from enhanced evaporation rates over the Atlantic as sea surface temperatures have risen, is one possible explanation for the decline in sunshine.

A strong negative correlation was confirmed between sunshine factors from ground‐based observations and satellite‐based cloud factors over Ireland. In addition, it was found that cloud factors over Ireland correlated well with cloud factors over large oceanic areas such as the North Atlantic and mid‐high latitudes generally. Thus cloud factors (and similarly sunshine factors) from regions on the boundaries of large oceans which lie in the direction of the prevailing wind could be useful in determining the long‐term changes in cloud factors over more extended areas. Knowledge of such long term variability in the Earth's cloud cover is important input information for modelling past climate change.

The importance of cosmic rays as a link between solar activity and climate was assessed from a study of the ISCCP‐D2 satellite cloud factors and Irish sunshine data. Whilst these results confirmed the strong correlation between total cloud factor and cosmic rays over non‐tropical oceans between 1984 and 1991 previously reported, it was found that this correlation did not hold in the subsequent period 1991–1994. Other work has established a link through specifically low cloud.

Indirect evidence of cloud formation by cosmic rays from a variation in the sunshine factor following Forbush decreases, and over the sunspot cycle, was mostly negative. Although a dip at seven years past sunspot minimum is evident in the sunshine factor for all four sites and in most seasons, it is of marginal statistical significance. Copyright © 2001 Royal Meteorological Society
Classification of rainfall variability by using artificial neural networks
Authors: Michaelides Silas Chr. , Pattichis Constantinos S. , Kleovoulou Georgia
Published: August 2002

In this paper, the usefulness of artificial neural networks (ANNs) as a suitable tool for the study of the medium and long‐term climatic variability is examined. A method for classifying the inherent variability of climatic data, as represented by the rainfall regime, is investigated. The rainfall recorded at a climatological station in Cyprus over a long time period has been used in this paper as the input for various ANN and cluster analysis models. The analysed rainfall data cover the time span 1917–1995. Using these values, two different procedures were followed for structuring the input vectors for training the ANN models: (a) each 1‐year subset consisting of the 12 monthly elements, and (b) each 2‐year subset consisting of the 24 monthly elements. Several ANN models with a varying number of output nodes have been trained, using an unsupervised learning paradigm, namely, the Kohonen's self‐organizing feature maps algorithm. For both the 1‐ and 2‐year subsets, 16 classes were empirically considered as the optimum for computing the prototype classes of weather variability for this meteorological parameter. The classification established by using the ANN methodology is subsequently compared with the classification generated by using cluster analysis, based on the agglomerative hierarchical clustering algorithm. To validate the classification results, the rainfall distributions for the more recent years 1996, 1997 and 1998 were utilized. The respective 1‐ and 2‐year distributions for these years were assigned to particular classes for both the ANN and cluster analysis procedures. Compared with cluster analysis, the ANN models were more capable of detecting even minor characteristics in the rainfall waveshapes investigated, and they also performed a more realistic categorization of the available data. It is suggested that the proposed ANN methodology can be applied to more climatological parameters, and with longer cycles. Copyright © 2001 Royal Meteorological Society
The intertropical convergence zone of the eastern Pacific revisited
Authors: Hastenrath Stefan
Published: August 2002

The Intertropical Convergence Zone (ITCZ) complex over the eastern Pacific is re‐examined from the NCEP–NCAR 40 year reanalysis and other data. Consistent with earlier work, the new analysis yields for July–August: a surface position of the near‐equatorial wind confluence at 12°N; the cross‐equatorial flow changing from divergent to convergent at the latitude of recurvature from southeasterly to southwesterly; strongest convergence in the surface layer to the south of the wind confluence, with this feeding vigorous ascending motion and compensating divergence in the upper troposphere; and the interface between cross‐equatorial flow and northeast trades sloping southward at 1 : 1500. An easterly speed maximum in the mid troposphere over the equator is consistent with the 4 year rawin record at Galapagos. The new coarse‐resolution dataset fails to capture a well‐developed Intertropical Divergence Zone. The annual cycle features for the wind confluence and the ITCZ a position closest to the equator in February, a northward migration to June, southward shift in July and August, and a northernmost location in September. This behaviour is paralleled by maxima in the frequency of the Temporal weather systems and rainfall on the Pacific side of Central America in June and September. Regarding the climatic variability, with an anomalously far southerly position of the wind confluence, Central American rainfall tends to be deficient, and such a combination of departures is common in the warm phase of the southern oscillation. The long‐term evolution is characterized by a warming trend of equatorial Pacific waters and weakening of cross‐equatorial wind, while trends in the latitude position of the wind confluence and in Central American rainfall are not significant. Copyright © 2002 Royal Meteorological Society.
Preparation of chlorin e6–monoclonal antibody conjugate and its effect for photodynamic therapy
Authors: OGURA SHUN-ICHIRO , FUJITA YUTAKA , KAMACHI TOSHIAKI , OKURA ICHIRO
Published: August 2002

Chlorin e6 ( Ce 6) was conjugated with anti-tumor monoclonal antibody ( IgG 2 b ) to increase its binding affinity for tumors. The Ce 6 was activated by N -hydroxysuccinimide and directly conjugated with IgG 2 b ( IgG 2 b – Ce 6) via peptide bonds. An average of 11 Ce 6 molecules were coupled to each IgG2b molecule. IgG 2 b – Ce 6 showed high cellular uptake in tumor cells and high photocytotoxicity. These results indicate IgG 2 b – Ce 6 is a good photosensitizer with high binding affinity to tumor cells.
Timing and significance of mid‐Holocene glacier advances in northern and central Iceland
Authors: Kirkbride Martin P. , Dugmore Andrew J.
Published: August 2002

Tephrochronology is used to date mid‐Holocene moraines in Iceland. In the Granavatn cirque (Tröllaskagi Peninsula) the H‐4 tephra (ca. 3830 yr BP) lies within sediment accumulated against the distal slope of a lateral moraine, providing a minimum age for glaciation, and the absence of H‐5 (ca. 5950 yr BP) provides a maximum age. By implication, the cirque was glaciated in the early Neoglacial period. A large rock glacier, the development of which post‐dates the moraine, probably formed within the ‘Little Ice Age’ (LIA) of the sixteenth to nineteenth centuries ad. At Eystri‐Loðmundarjökull in central Iceland, frozen colluvium containing the H‐3 (ca. 2900 yr BP) and H‐4 tephras provides a minimum age of ca. 3830 yr BP for two terminal moraines, and a maximum age of ca. 2900 yr BP for a third. The older moraines are correlated with the Vatnsdalur I/Drangagíl advances (ca. 4700 yr BP and ≥ 4500 yr BP respectively) and the Begisárdalur I advance (ca. 4200 yr BP). They imply that early Neoglacial advances throughout Iceland were locally more extensive than those of the LIA. The apparent LIA Holocene glacial maximum may reflect (i) selective sampling of large ice‐cap‐outlet glaciers, where the preservation potential of pre‐LIA deposits is low, and (ii) reliance on lichenometric dating, which has a restriced temporal range. Copyright © 2001 John Wiley & Sons, Ltd.
Raman spectroscopy of descloizite and mottramite at 298 and 77 K
Authors: Frost Ray L. , Williams Peter A. , Theo Kloprogge J. , Leverett P.
Published: August 2002

The Raman spectra of the isomorphous series descloizite [PbZn(VO4)(OH)] and mottramite [PbCu(VO4) (OH)] were obtained at 298 and 77 K. The Raman band at 844 cm−1, assigned to the ν1 symmetric (VO4−) stretching mode for descloizite, is shifted to 814 cm−1 for mottramite. The ν3 mode of descloizite is observed as a single band at 777 cm−1 but this mode is more complex for mottramite with three bands observed in the 77 K spectrum at 811, 785 and 767 cm−1. The bending mode (ν2) is observed at 437 cm−1 for descloizite and at 426 cm−1 for mottramite. The ν3 region is complex for both minerals and this is attributed to symmetry reduction of the vanadate unit from Td to Cs. Collecting Raman spectra at 77 K allowed better band separation with observation of additional bands ascribed to the removal of degeneracy. Copyright © 2001 John Wiley & Sons, Ltd.