bluuebunny/crossref_metadata_2025 huggingface dataset:
Regional dynamics of the fMRI‐BOLD signal response to hypoxia‐hypercapnia in the rat brain
Authors: Kannurpatti Sridhar S. , Biswal Bharat B. , Hudetz A.G.
Published: May 2003

Purpose

To examine the regional blood oxygenation level‐dependent (BOLD) signal response to rapid changes in arterial oxygen tension.

Materials and Methods

Functional MR imaging (fMRI) was carried out in five male Sprague‐Dawley rats anesthetized with Sodium Pentobarbital. Rats were subjected to different durations of apnea as a rapid, graded, and reversible hypoxic‐hypercapnic stimulus. Dynamics of the BOLD signal response were studied on a pixel‐by‐pixel basis in the cerebral cortex, hippocampus, third ventricle, and thalamus in the rat brain.

Results

Apnea induced a BOLD signal drop in all the brain regions studied, the magnitude of which increased with longer durations of the stimulus. The signal recovered to preapnic baseline levels after resumption of normal ventilation. Regional variation in the BOLD signal dynamics was observed with the magnitude of the BOLD signal change in the hippocampus being the least, followed by a relatively larger change in the thalamus, cerebral cortex, and third ventricle. The time (t0) for the signal change after the onset of the stimulus was estimated for every pixel. Time delay maps generated show the highest onset time values in the hippocampus followed by the thalamus, cerebral cortex, and third ventricle.

Conclusion

The regional dynamics of the BOLD signal in the brain in response to apnea may vary depending on the rate of oxygen metabolism in addition to cerebral blood flow (CBF). J. Magn. Reson. Imaging 2003;17:641–647. © 2003 Wiley‐Liss, Inc.
Functional evaluation of normothermic ischemia and reperfusion injury in dog kidney by combining MR diffusion‐weighted imaging and Gd‐DTPA enhanced first‐pass perfusion
Authors: Liu Ai‐Shi , Xie Jing‐Xia
Published: May 2003

Purpose

To evaluate functional alterations of renal ischemia and reperfusion injury using MR diffusion‐weighted imaging and dynamic perfusion imaging.

Materials and Methods

Twelve dogs were randomly divided into four groups. Animal renal ischemia was respectively induced for 30 (group 1), 60 (group 2), 90 (group 3), and 120 (group 4) minutes by left renal artery ligation under anesthesia. Using a 1.5 T MR system, true‐FISP, TSE, EPI, and DWI sequences were acquired in five different periods; specifically, pre‐ischemia, onset‐ischemia, late ischemia, onset‐reperfusion, and post‐reperfusion. Moreover, a turbo‐FLASH sequence (TR/TE/TI/FA = 5.8/3.2/400 msec/10°) with a temporal resolution of 1.16 seconds was acquired. Signal intensity (SI) was measured in the cortex, outer medulla, and inner medulla of kidney. Apparent diffusion coefficient (ADC) values were calculated, and SI was plotted as a function of time.

Results

In all animals, significant SI changes of the left kidney on T2/T2*WI were detected following ischemia‐reperfusion insult compared to corresponding values of the right kidney. Following ligation, the ADC values decreased in all layers of the left kidney. Immediately after the release of ligation, ADC values in both outer and inner medulla of the left kidney remained lower than those of the right kidney in those animals which were induced with renal ischemia for 60, 90, and 120 minutes. In all groups, a uniphasic enhancement pattern was observed in the outer and inner medulla of the left kidney, accompanied by a decrease of the area under the curve.

Conclusion

Our results suggest that MR diffusion‐weighted imaging and dynamic perfusion imaging are useful in identifying renal dysfunction following normothermic ischemia and reperfusion injury. J. Magn. Reson. Imaging 2003;17:683–693. © 2003 Wiley‐Liss, Inc.
Contrast‐enhanced MR angiography of the run‐off vasculature: Intraindividual comparison of gadobenate dimeglumine with gadopentetate dimeglumine
Authors: Knopp Michael V. , Giesel Frederik L. , von Tengg‐Kobligk Hendrik , Radeleff Jannis , Requardt Martin , Kirchin Miles A. , Hentrich Hans‐Rainer
Published: May 2003

Purpose

To compare intraindividually gadobenate dimeglumine (Gd‐BOPTA) with gadopentetate dimeglumine (Gd‐DTPA) for multi‐station MR Angiography of the run‐off vessels.

Materials and Methods

Twenty‐one randomized healthy volunteers received either Gd‐BOPTA or Gd‐DTPA as a first injection and then the other agent as a second injection after a minimum interval of 6 days. Each agent was administered at a dose of 0.1 mmol/kg bodyweight followed by a 25‐mL saline flush at a single constant flow rate of 0.8 mL/second. Images were acquired sequentially at the level of the pelvis, thigh, and calf using a fast three‐dimensional (3D) gradient echo sequence. Source, subtracted source, maximum intensity projection (MIP), and subtracted MIP image sets from each examination were evaluated quantitatively and qualitatively on a segmental basis involving nine vascular segments.

Results

Significantly (P < 0.05) higher signal‐to‐noise and contrast‐to‐noise ratios were noted for Gd‐BOPTA compared to Gd‐DTPA, with the more pronounced differences evident in the more distal vessels. Qualitative assessmentrevealed no differences in the abdominal vasculature, a preference for Gd‐BOPTA in the pelvic vasculature, and markedly better performance for Gd‐BOPTA in the femoral and tibial vasculature. Summation of individual diagnostic quality scores for each segment revealed a significantly (P = 0.0001) better performance for Gd‐BOPTA compared to Gd‐DTPA.

Conclusion

Greater vascular enhancement of the run‐off vasculature is obtained after Gd‐BOPTA, particularly in the smaller more distal vessels. Enhancement differences are not merely dose dependent, but may be due to different vascular enhancement characteristics of the agents. J. Magn. Reson. Imaging 2003;17:694–702. © 2003 Wiley‐Liss, Inc.
Visualization and quantification of renal R2* changes during water diuresis
Authors: Zuo Chun S. , Rofsky Neil M. , Mahallati Houman , Yu Jeongsik , Zhang Ming , Gilbert Scott , Epstein Franklin H.
Published: May 2003

Purpose

To refine and evaluate methods for analysis of renal blood oxygenation level dependent (BOLD) MRI data.

Materials and Methods

Color R2* maps and regions‐of‐interest (ROIs) on the borderline between cortex and medulla were applied to renal BOLD MRI data of a group of 13 young female subjects.

Results

The distribution of R2* within the kidneys was heterogeneous and the response of human kidneys to water diuresis was patchy. R2* values at the cortico‐medullary border region have a smaller variation than in wider cortical or medullary regions and are sensitive to physiological changes produced by water diuresis.

Conclusion

These methods provide improved visualization of the regional distribution of R2* and its variations and more precise quantification of the changes in renal R2* produced by water diuresis. J. Magn. Reson. Imaging 2003;17:676–682. © 2003 Wiley‐Liss, Inc.
Proton spectroscopic metabolite signal relaxation times in preterm infants: A prerequisite for quantitative spectroscopy in infant brain
Authors: Kugel Harald , Roth Bernhard , Pillekamp Frank , Krüger Karsten , Schulte Oliver , von Gontard Alexander , Benz‐Bohm Gabriele
Published: May 2003

Purpose

To determine relaxation times of metabolite signals in proton magnetic resonance (MR) spectra of immature brain, which allow a correction of relaxation that is necessary for a quantitative evaluation of spectra acquired with long TE. Proton MR spectra acquired with long TE allow a better definition of metabolites as N‐acetyl aspartate (NAA) and lactate especially in children.

Materials and Methods

Relaxation times were determined in the basal ganglia of 84 prematurely born infants at a postconceptional age of 37.8 ± 2.2 (mean ± SD) weeks. Metabolite resonances were investigated using the double‐spin‐echo volume selection method (PRESS) at 1.5 T. T1 was determined from intensity ratios of signals obtained with TRs of 1884 and 6000 msec, measured at 3 TEs (25 msec, 136 msec, 272 msec). T2 was determined from signal intensity ratios obtained with TEs of 136 msec and 272 msec, measured at 2 TR. Taking only long TEs reduced baseline distortions by macromolecules and lipids. For myo‐inositol (MI), an apparent T2 for short TE was determined from the ratio of signals obtained with TE = 25 msec and 136 msec. Intensities were determined by fitting a Lorentzian to the resonance, and by integration.

Results

Relaxation times were as follows: trimethylamine‐containing compounds (Cho): T1 = 1217 msec/T2 = 273 msec; total creatine (Cr) at 3.9 ppm: 1010 msec/111 msec; Cr at 3.0 ppm: 1388 msec/224 msec; NAA: 1171 msec/499 msec; Lac: 1820 msec/1022 msec; MI: 1336 msec/173 msec; apparent T2 at short TE: 68 msec.

Conclusion

T1 and T2 in the basal ganglia of premature infants do not differ much from previously published data from basal ganglia of older children and adults. T2 of Cho was lower than previous values. T2 of Cr at 3.9 ppm and Lac have been measured under different conditions before, and present values differ from these data. J. Magn. Reson. Imaging 2003;17:634–640. © 2003 Wiley‐Liss, Inc.
Double inversion black‐blood fast spin‐echo imaging of the human heart: A comparison between 1.5T and 3.0T
Authors: Greenman Robert L. , Shirosky John E. , Mulkern Robert V. , Rofsky Neil M.
Published: May 2003

Purpose

To evaluate the effectiveness of blood suppression and the quality of black‐blood cardiac images acquired at 3.0 Tesla using a double‐inversion recovery fast spin‐echo sequence by comparing data acquired at 3.0T to data acquired at 1.5T.

Materials and Methods

Black‐blood T2‐weighted fast spin‐echo images of the heart were acquired from five normal volunteers at 1.5T and five normal volunteers at 3.0T. Region‐of‐interest signal intensity measurements were performed at several locations in the suppressed blood regions of the left and right ventricles and around the left ventricle walls to assess the effectiveness and uniformity of the blood suppression, the myocardial signal‐to‐noise ratio (SNR), and the signal uniformity at both field strengths. B1 field maps were produced in phantoms and in subjects at both field strengths.

Results

Blood suppression performance is equivalent at 1.5T and 3.0T. The improvement in SNR at 3.0T compared with 1.5T is less than has been predicted in previous studies. The signal uniformity is significantly poorer at 3.0T than at 1.5T due to dielectric effects and shorter radio frequency wavelengths (P < 0.005).

Conclusion

Spin‐echo and spin‐echo echo‐train sequences that perform well at 1.5T will produce large signal variations in the chest cavity at 3.0T without modifications. B1 insensitive methods must be explored and implemented for spin‐echo sequences to fully realize the advantages of using these sequences for high‐field MRI. J. Magn. Reson. Imaging 2003;17:648–655. © 2003 Wiley‐Liss, Inc.
Improvement of image quality of non‐invasive coronary artery imaging with magnetic resonance by the use of the intravascular contrast agent Clariscan™ (NC100150 injection) in patients with coronary artery disease
Authors: Klein Christoph , Schalla Simon , Schnackenburg Bernhard , Bornstedt Axel , Hoffmann Volker , Fleck Eckart , Nagel Eike
Published: May 2003

Purpose

To assess the feasibility of Clariscan™, an intravascular contrast agent, for free breathing, navigator assisted, high resolution, three‐dimensional‐magnetic resonance coronary angiography (MRCA) in patients, as extracellular contrast agents are unfavorable for the improvement of image quality.

Materials and Methods

MRCA was performed in 10 patients with known coronary artery disease (CAD) with (1–5 mg Fe/kg body weight) and without contrast agent.

Results

Compared to unenhanced images, Clariscan™ did not improve signal‐to‐noise (SNR) or contrast‐to‐noise ratios (CNR) compared to fat or myocardium in the proximal parts of the coronary arteries. However, when analyzing the peripheral parts (>4 cm from origin), CNRfat and CNRmyo improved up to a factor of 1.81 and 5.85, respectively, at a dose of 3 mg Fe/kg body weight, while SNR did not reach statistical significance. The visible length of the coronary arteries was improved from 49 ± 18 mm to 73 ± 33 mm. The proximal diameter was reduced from 3.6 ± 0.8mm to 3.2 ± 0.8 mm, representing more closely the diameter of 3.1 ± 0.7 mm measured by quantitative coronary angiography. Of 11 significant stenoses (>50%), eight were identified in the enhanced compared to six in the unenhanced images.

Conclusion

The use of Clariscan™ at a dose of 2–3 mg Fe/kg body weight improves image quality of three‐dimensional‐MRCA, especially in the peripheral segments, and, thus, the diagnostic accuracy for the detection of CAD. J. Magn. Reson. Imaging 2003;17:656–662. © 2003 Wiley‐Liss, Inc.
Difference in prognosis between patients infected with hepatitis B virus with genotype B and those with genotype C in the Okinawa Islands: A prospective study
Authors: Nakayoshi Tomokuni , Maeshiro Tatsuji , Nakayoshi Tomofumi , Nakasone Hiroki , Sakugawa Hiroshi , Kinjo Fukunori , Orito Etsuro , Mizokami Masashi
Published: May 2003

The factors contributing to the prognosis of hepatitis B virus (HBV)‐ related chronic liver disease were assessed prospectively in 72 patients with chronic hepatitis B confirmed clinically and pathologically. A comparative study was undertaken between patients infected with genotype B and those with genotype C. During the follow‐up period, 13 (81.3%) of 16 patients with genotype B who were initially hepatitis B e antigen (HBeAg) positive became HBeAg negative and 14 (51.9%) of 27 with genotype C became HBeAg negative. HBeAg had been cleared in 8 (61.5%) of 13 patients with genotype B within the first 2 years of the follow‐up, but in only one (7.1%) of 14 with genotype C (P < 0.05). Four (11.4%) of 35 patients with genotype B had progressed to cirrhosis, whereas, 12 (32.4%) of 37 patients with genotype C progressed to cirrhosis, including two patients with hepatocellular carcinoma. Multivariate analysis showed that difference in HBV genotype influenced significantly either the clearance of HBeAg or the development of cirrhosis. In conclusion, HBeAg was cleared from sera more frequently and earlier in patients with genotype B compared with those with genotype C, and development of cirrhosis occurred less frequently in patients with genotype B compared with those with genotype C. Thus, HBV genotypes may influence the prognosis of HBV‐related chronic liver disease. J. Med. Virol. 70:350–354, 2003. © 2003 Wiley‐Liss, Inc.
Performance of two commercially available sequence‐based HIV‐1 genotyping systems for the detection of drug resistance against HIV type 1 group M subtypes
Authors: Beddows Simon , Galpin Sarah , Kazmi Shamim H. , Ashraf Ambreen , Johargy Ayman , Frater Alexander J. , White Natalie , Braganza Ruth , Clarke John , McClure Myra , Weber Jonathan N.
Published: May 2003

The use of genotyping assays for the detection and evaluation of drug resistance mutations within the polymerase gene of human immunodeficiency virus type 1 (HIV‐1) is becoming increasingly relevant in the clinical management of HIV‐1 infection. However, genotypic resistance assays available currently have been optimised for genetic subtype B strains of the virus and many clinical centres are presented with strains from subtypes A, C, and D. In the present report, we compare the performance of two sequence‐based commercially available kits, the ViroSeq Genotyping System (Applied Biosystems, Foster City, CA) and the TruGene HIV‐1 Genotyping Kit (Visible Genetics, Toronto, Ontario) against a panel of 35 virus isolates from HIV‐1 Group M (subtypes A–J). Full‐length consensus sequences were generated by the ViroSeq genotyping system for 26 of 31 (83.8%) of the isolates tested, in contrast to the TruGene genotyping system, which generated 16 of 30 (53%) usable sequences overall. Overall, subtype B isolates were sequenced with a greater degree of success than non‐subtype B isolates. Discrepancies were found between the consensus sequences reported by each system for each sample (mean difference 1.0%; range 0.0–3.2%), but these appeared to be random and did not affect interpretation of the major resistance codons. In addition, both systems were able to amplify template RNA from low copy viral load plasma samples (102–103 RNA copies/ml) taken from a random selection of patient samples encompassing subtypes A–C. While the availability of these genotyping systems should facilitate studies of HIV‐1 drug resistance in countries in which these subtypes are prevalent, the performance against subtypes other than B needs to be improved. J. Med. Virol. 70:337–342, 2003. © 2003 Wiley‐Liss, Inc.
Genetic analysis of HAV strains recovered from patients with acute hepatitis from Southern Italy
Authors: Chironna Maria , Grottola Antonella , Lanave Cecilia , Villa Erica , Barbuti Salvatore , Quarto Michele
Published: May 2003

Southern Italy is an endemic area for HAV infection contributing to the majority of Italian hepatitis A cases. Using molecular analysis, HAV strains have been classified in distinct genotypes and subgenotypes. To characterize HAV wild‐type strains circulating in Southern Italy, sequence analysis of VP3‐VP1 and VP1/2A junction regions of HAV isolates recovered from 25 patients with acute hepatitis during 2000 and 2001 was carried out. HAV isolates showed a degree of identity, after pairwise comparison with one another, ranging from 91.9–100% in the VP3‐VP1 junction region and 89.9–100% in the VP1/2A junction region. All strains belonged to genotype I, with 84% (21/25) of samples clustering in subgenotype IA and 16% (4/25) in subgenotype IB. Cocirculation of subgenotypes IA and IB was observed among isolates from 2000, whereas all strains from 2001 were subgenotype IA. In addition, the subgenotype IA strains formed different clusters, one of which was related closely to some Cuban strains, showing a percent similarity of 98.8% in the 168‐base pair segment encompassing the VP1/2A junction and the same amino acid substitution. The latter finding suggests that this subgenotype variant circulates also in the Mediterranean area. The results of the phylogenetic analysis confirm the genetic heterogeneity among HAV strains in Western Europe. J. Med. Virol. 70:343–349, 2003. © 2003 Wiley‐Liss, Inc.
HBe antigen loss during lamivudine therapy is not caused by mutations in precore and core promoter genes in patients with chronic hepatitis B
Authors: Suzuki Fumitaka , Tsubota Akihito , Arase Yasuji , Suzuki Yoshiyuki , Akuta Norio , Hosaka Tetsuya , Someya Takashi , Kobayashi Masahiro , Saitoh Satoshi , Ikeda Kenji , Kobayashi Mariko , Matsuda Marie , Satoh Junko , Takagi Kimiko , Kumada Hiromitsu
Published: May 2003

HBe antigen (HBeAg) loss or seroconversion can occur during lamivudine therapy. The purpose of this study was to analyze nucleotide sequences in precore and core promoter regions, and examine the influence of mutations in these regions on the disappearance of HBeAg during lamivudine therapy. Serial serum samples were obtained from 51 patients (HBeAg loss in 26 patients) at commencement of therapy (baseline) and after 1 year of lamivudine therapy. Serum samples were amplified with PCR and nucleotide sequences of HBV were analyzed. At baseline, a precore stop codon mutation (A1896) was identified in 8 of 26 HBeAg loss patients and in 8 of 25 HBeAg non‐loss patients. At 1 year, precore mutation was observed in 4 of 14 patients analyzed who showed HBeAg loss. At 1 year, however, a precore mutation was observed also in 3 of 9 analyzed patients who showed no HBeAg loss. Core promoter mutations were noted in 21 of 26 HBeAg loss patients and in 20 of 25 HBeAg non‐loss patients. At 1 year, core promoter mutations were noted in 11 of 14 HBeAg loss patients and in 8 of 9 HBeAg non‐loss patients. Our data suggested that during lamivudine therapy, core promoter and precore mutations do not influence HBeAg loss or seroconversion but may reduce the viral level upon HBeAg loss or seroconversion. J. Med. Virol. 70:355–360, 2003. © 2003 Wiley‐Liss, Inc.
Characterisation of the differences between hepatitis C virus genotype 3 and 1 glycoproteins
Authors: Shaw Megan L. , McLauchlan John , Mills Peter R. , Patel Arvind H. , McCruden Elizabeth A.B.
Published: May 2003

Sequence variation in the envelope E1 and E2 glycoproteins of hepatitis C virus (HCV) could account for differences in disease pathogenesis in patients infected with different genotypes. A cDNA encoding the structural region of the hepatitis C polyprotein was constructed to match the majority sequence of viral RNA extracted from a patient infected with genotype 3a (designated strain HCV3a‐Gla). The principal differences predicted between E2 of HCV3a‐Gla and the corresponding H77c genotype 1a protein were that the former contained six more amino acids (361 vs. 355), but it had one fewer glycosylation site. Expression studies showed that, in common with the H77c glycoproteins, E1 and E2 from HCV3a‐Gla localised to the endoplasmic reticulum (ER) membrane in both Huh‐7 and BHK tissue culture cells and interacted to form native complexes. Analysis of the cross‐reactivity of antibodies raised against glycoproteins of genotype 1a strains showed that three of five monoclonal antibodies that recognise linear epitopes were able to detect E2 from strain HCV3a‐Gla. However, neither conformational E2 antibodies nor antibodies raised against E1 were able to detect the HCV3a‐Gla glycoproteins. In receptor binding assays, E2 of HCV3a‐Gla consistently failed to bind CD81, a putative cell receptor for HCV. Absence of binding to CD81 and lack of recognition by most antibodies raised to genotype 1a glycoproteins indicate important differences between these glycoproteins representative of genotypes 3a and 1a. These may be pertinent to the differences in response to interferon therapy and the prevalence of steatosis reported in patients infected with these genotypes. J. Med. Virol. 70:361–372, 2003. © 2003 Wiley‐Liss, Inc.
Clinical features and progression of perinatally acquired hepatitis C virus infection
Authors: Resti Massimo , Jara Paloma , Hierro Loreto , Azzari Chiara , Giacchino Raffaella , Zuin Giovanna , Zancan Lucia , Pedditzi Sabrina , Bortolotti Flavia
Published: May 2003

The purpose of this prospective‐retrospective study was to provide information about the clinical features and progression of hepatitis C virus (HCV) infection transmitted perinatally. Seventy children born to HCV infected woman were enrolled consecutively in five European centers between 1990 and 1999, provided they had HCV RNA in the serum during the first year of life and/or were still anti‐HCV positive at 18 months. Sixty‐two infants were followed up to 24 months of age or more (range, 24 months–11 years; average, 4.8 ± 2.3 years). A wide range of ALT elevation was observed in 93% of the infants in the first year of life. During the follow‐up, a sustained ALT normalization with loss of HCV RNA was seen in 12/62 (19%) of the children within 30 months of life; 66% of the infants had developed an ALT peak greater than 5× normal at onset (vs. 28% of children with persistent viremia; P < 0.05), and 50% had HCV genotype 3 (vs. 17% of viremic children). Conversely the cumulative probability of chronic progression was 81%. Chronic infection was asymptomatic and liver disease was mild in all 11 children who underwent a biopsy. In conclusion the early stage of acquired perinatally HCV infection is characterized by a wide range of ALT abnormalities, suggesting the interaction of multiple host and virus factors. The chronic progression rate of infection is high, but the associated liver disease is usually mild. High ALT levels at onset seem to offer greater opportunity of biochemical remission and loss of viremia during follow‐up. J. Med. Virol. 70:373–377, 2003. © 2003 Wiley‐Liss, Inc.
Natural histories of hepatitis C virus infection in men and women simulated by the Markov model
Authors: Tanaka Junko , Kumada Hiromitsu , Ikeda Kenji , Chayama Kazuaki , Mizui Masaaki , Hino Kunihiko , Katayama Keiko , Kumagai Junko , Komiya Yutaka , Miyakawa Yuzo , Yoshizawa Hiroshi
Published: May 2003

The Markov model was introduced to simulate natural histories of hepatitis C virus (HCV) infection in men and women. The data set was constructed on 942 HCV carriers who were examined at least once a year without receiving antiviral therapies. Based on 2,251 patient‐year data, the probabilities of transition between any two of the four clinical states, i.e., asymptomatic carrier state, chronic hepatitis, liver cirrhosis and hepatocellular carcinoma in 1 year were calculated. Hepatocellular carcinoma was defined as the absorbing state from where no transitions occur. Probability matrices thus obtained on six each subsets of HCV infection (asymptomatic carrier state, chronic hepatitis and liver cirrhosis in men and women) in their forties, fifties, and sixties, were used to simulate long‐term outcomes of HCV infection. Male asymptomatic carriers aged 40 years were expected to retain the asymptomatic carrier state in 2.6%, evolve into chronic hepatitis in 48.4%, liver cirrhosis in 14.6% and hepatocellular carcinoma in 34.4% after 30 years when they reached 70 years of age, in contrast to 1.9%, 45.3%, 32.8% and 20.0%, respectively, of female asymptomatic carriers. Likewise, male patients with chronic hepatitis aged 40 years were expected to remain with chronic hepatitis in 43.8%, evolve into liver cirrhosis in 15.0% and hepatocellular carcinoma in 41.1%, contrasting with 38.9%, 32.7% and 22.0%, respectively, of female patients during 30 years. The Markov model could simulate the outcomes of 153 HCV carriers identified among blood donors after 5 years. The Markov simulation would help in assessing the long‐term outcome of HCV infection and making decisions in the management of HCV carriers toward prevention of hepatocellular carcinoma. J. Med. Virol. 70:378–386, 2003. © 2003 Wiley‐Liss, Inc.
Hepatitis C virus infection among noninjecting drug users in New York City
Authors: Koblin Beryl A. , Factor Stephanie H. , Wu Yingfeng , Vlahov David
Published: May 2003

The prevalence of hepatitis C virus (HCV) infection among noninjecting drug users has been reported to be higher than in the general population, but the reasons for this observation remain unclear. Noninjecting drug users aged 15–40 years and who used drugs for no longer than 10 years were enrolled in the study. The participants were interviewed about risk behaviors and had specimens drawn for serological testing. Of 276 enrolled, 4.7% were infected with HCV. Drug users who had ever sniffed or snorted heroin in combination with cocaine were significantly more likely to be infected with HCV compared with those who never sniffed or snorted heroin with cocaine. No other drug use or sexual risk behaviors were found to be associated with HCV infection. These findings suggest that sniffing or snorting heroin with cocaine may explain the increase frequently found in HCV infection among noninjectors, but further studies are necessary. J. Med. Virol. 70:387–390, 2003. © 2003 Wiley‐Liss, Inc.
Sialic acid receptor specificity on erythrocytes affects detection of antibody to avian influenza haemagglutinin
Authors: Stephenson I. , Wood J.M. , Nicholson K.G. , Zambon M.C.
Published: May 2003

Haemagglutination‐inhibition tests (HI) are used to detect increases in influenza antibody in serum. However, they are relatively insensitive for the detection of human antibody responses to avian haemagglutinin, even in the presence of high titres of neutralising antibody after confirmed infection or vaccination. Human influenza viruses bind preferentially sialic acid containing N‐acetylneuraminic acid α2,6‐galactose (SAα2,6Gal) linkages while avian and equine viruses bind preferentially those containing N‐acetylneuraminic acid α2,3‐galactose (SAα2,3Gal) linkages. Increasing the proportion of SAα2,3Gal linkages on the erythrocytes used, by enzymatic modification or change of species, improves the ability of erythrocytes to bind to avian influenza strains and thereby improves the sensitivity of detection of antibody to avian and equine HA in a range of mammalian and human sera using HI tests. J. Med. Virol. 70:391–398, 2003. © 2003 Wiley‐Liss, Inc.
Reconstitution of lymphocyte populations and cytomegalovirus viremia or disease after allogeneic peripheral blood stem cell transplantation
Authors: Gutiérrez Antonio , Muñoz Isabel , Solano Carlos , Benet Isabel , Gimeno Concepción , Marugán Isabel , Gea María Dolores , García‐Conde Javier , Navarro David
Published: May 2003

Early reconstitution of lymphoid populations was monitored by immunophenotyping in 57 allogeneic peripheral blood stem cell (allo‐PBSC) transplant patients either with or without cytomegalovirus (CMV) viremia or disease. Cell counts for total lymphocytes and CD4+ T cells above the percentile 60th at day 14 postransplant were associated significantly with CMV viremia‐free survival within 120 days after transplant. Recovery of total lymphocyte, CD3+, and CD8+ T‐cell counts proceeded at a more rapid rate in CMV viremic patients than in nonviremic patients, irrespective of whether preemptive treatment with ganciclovir had been prescribed. Significant expansion of CD8+ and CD8+ CD57+ T‐cell subsets was associated with recovery from viremia and no progression to CMV disease. Immunophenotyping may provide useful information for the clinical management of CMV infection in allo‐PBSC transplant recipients. J. Med. Virol. 70:399–403, 2003. © 2003 Wiley‐Liss, Inc.
Molecular epidemiological study of dengue virus type 1 in Taiwan
Authors: Hwang Kao‐Pin , Chu Pei‐Yu , Tung Yi‐Ching , Wang Heng‐Lin , Yueh Yi‐Yun , Wu Ying‐Chang , Chin Chuan , Lin Kuei‐Hsiang
Published: May 2003

Taiwan has experienced several major outbreaks of dengue (DEN) virus since 1981. The predominant virus type involved has been dengue virus type one (DEN‐1), which first appeared in 1987. To understand the molecular epidemiology of this virus, 15 strains of DEN‐1 isolated during 1987–1991 and 1994–1995, including 11 epidemic strains, two sporadic strains, and two imported strains have been studied. Fragments of 490 nucleotides (nt) from the E/NS1 junction were amplified by reverse transcription‐polymerase chain reaction and the nt sequences were determined. Of the 490 nt of the E/NS1 junction, 240 nt (nt 2282–2521) were aligned and compared. Nucleotide substitutions were found at 54 positions among 15 isolates. Most nt changes were synonymous substitutions, and only three amino acid changes were found. A total of 61 strains isolated worldwide were analyzed by the Neighbor‐joining method, and separated phylogenetically into three distinct genotypes, I–III. Genotype I comprised isolates from Japan and Hawaii collected in the 1940s. Genotype II included most strains isolated from Asia in 1977–1995. Genotype III consisted of isolates from three continents in 1964–1995: Asia, the Americas, and Africa. Genotype III was divided further into two subgenotypes, IIIA and IIIB. Most recent isolates from Taiwan, except for the sporadic strain isolated in 1995, were similar genetically and have been classified as Genotype II. J. Med. Virol. 70:404–409, 2003. © 2003 Wiley‐Liss, Inc.
Latency pattern of Epstein‐Barr virus and methylation status in Epstein‐Barr virus‐associated hemophagocytic syndrome
Authors: Yoshioka Mikio , Kikuta Hideaki , Ishiguro Nobuhisa , Endo Rika , Kobayashi Kunihiko
Published: May 2003

Expression of different panels of latent gene transcripts is controlled by usage of three distinct Epstein‐Barr virus (EBV) nuclear antigen (EBNA) promoters (Wp, Cp, and Qp). EBV‐associated hemophagocytic syndrome, which is often a fatal disease and generally occurs after primary EBV infection, is characterized by monoclonal or oligoclonal proliferation of EBV‐infected T cells. The latency pattern and EBNA promoter (Wp, Cp, and Qp) usage in EBV‐infected cells from three patients with EBV‐associated hemophagocytic syndrome were examined by reverse transcription‐polymerase chain reaction (PCR). Three samples from the patients expressed EBER, EBNA1, EBNA2, latent membrane protein (LMP)1, and LMP2A transcripts. The transcripts of EBNA1 were initiated from not only Wp/Cp but also Qp. Lytic cycle Fp‐initiated EBNA1 and EBV lytic gene BZLF1 transcripts were not detected. The methylation statuses of three EBNA promoters in three patients with EBV‐associated hemophagocytic syndrome and in two patients with infectious mononucleosis were also analyzed using bisulfite PCR analysis. Wp was hypermethylated, and Qp was unmethylated in both diseases. Cp was highly methylated in EBV‐associated hemophagocytic syndrome, however, whereas Cp was almost unmethylated in infectious mononucleosis. These results suggest that there may be distinct EBV‐infected cell populations in EBV‐associated hemophagocytic syndrome, which exhibit different patterns of EBV latent gene expression. The methylation status in Cp and phenotype of EBV‐infected cells may be critical differences in EBV‐associated hemophagocytic syndrome and infectious mononucleosis. J. Med. Virol. 70:410–419, 2003. © 2003 Wiley‐Liss, Inc.
Molecular typing and epidemiology of enteroviruses identified from an outbreak of aseptic meningitis in Belgium during the summer of 2000
Authors: Thoelen Inge , Lemey Philippe , Van der Donck Ingrid , Beuselinck Kurt , Lindberg A. Michael , Van Ranst Marc
Published: May 2003

Non‐polio enteroviruses are the most common cause of aseptic meningitis worldwide. From May to September 2000, a major outbreak of aseptic meningitis occurred in Belgium. Cerebrospinal fluid samples (CSF) of 122 patients were found to contain enterovirus RNA using diagnostic RT‐PCR that targeted a 231‐bp gene fragment in the 5′ noncoding region. In addition, a molecular typing method was developed based on RT‐nested PCR and sequencing directly from CSFa 358‐bp fragment in the aminoterminal part of the VP1 capsid protein. To identify the enterovirus type, nucleotide sequences of the VP1 amplicons were compared to all the enterovirus VP1 sequences available in GenBank. Echovirus 30 (31.2%), echovirus 13 (23.8%), and echovirus 6 (20.5%) were identified most frequently during the epidemic. Coxsackievirus B5 was present in 15.6% of the samples, and could be subdivided in two distinct epidemic clusters, coxsackievirus B5a (10.7%) and B5b (4.9%). Other enteroviruses encountered were echovirus 16 (5.7%), echovirus 18 (1.6%), coxsackievirus B4 (0.8%) and echovirus 7 (0.8%). The high prevalence of echovirus 13, considered previously a rare serotype, indicates it is an emerging epidemic type. To verify the typing results and to explore further the intratypical genetic variation, phylogenetic analysis was carried out. Geographical clustering of most of the strains within each type and subtype could be observed. The RT‐nested PCR strategy, carried out directly on clinical samples, is a simple and rapid method for adequate molecular typing of the Group B enteroviruses causing aseptic meningitis. J. Med. Virol. 70:420–429, 2003. © 2003 Wiley‐Liss, Inc.
Enterovirus infection and activation of human umbilical vein endothelial cells
Authors: Saijets Salla , Ylipaasto Petri , Vaarala Outi , Hovi Tapani , Roivainen Merja
Published: May 2003

Gastrointestinal tract associated lymphoid tissue is considered to be the main replication site for enteroviruses. In order to invade tissues to reach pancreatic islets, cardiac muscles, and other secondary replication sites, the virus has to survive circulation in the blood and find a way to get through endothelial cells. In the present study, the susceptibility of human endothelial cells to infections caused by human parechovirus 1 and several prototype strains of enteroviruses, representing different species (human poliovirus, human enterovirus B and C), and acting through different receptor families was examined. Primary endothelial cells isolated from human umbilical vein by collagenase perfusion and also an established human endothelial cell line, HUVEC, were used. Primary endothelial cells were highly susceptible to several serotypes of enteroviruses (coxsackievirus A13, echoviruses 6, 7, 11, 30, and poliovirus 1). However, coxsackievirus A 9 and echovirus 1 infected only a few individual cells while human parechovirus 1 and coxsackie B viruses did not show evidence of replication in primary endothelial cells. In general, primary endothelial cells were more sensitive to infection‐induced cytolytic effect than HUVEC. Activation of endothelial cells by interleukin‐1β did not change the pattern of enterovirus infection. Immunofluorescence stainings of infected primary endothelial cells showed that expression of activation markers, E‐selectin, and intercellular adhesion molecule‐1, was clearly increased by several virus infections and the former molecule also by exposing cells to UV‐light inactivated coxsackieviruses. In contrast, human leukocyte antigen‐DR expression was not increased by virus infection. J. Med. Virol. 70:430–439, 2003. © 2003 Wiley‐Liss, Inc.
Human herpesvirus 7‐associated meningitis and optic neuritis in a patient after allogeneic stem cell transplantation
Authors: Yoshikawa Tetsushi , Yoshida Jun , Hamaguchi Motohiro , Kubota Toshinobu , Akimoto Shiho , Ihira Masaru , Nishiyama Yukihiro , Asano Yoshizo
Published: May 2003

A 9‐year‐old boy who received allogeneic stem cell transplantation began to vomit from day 10 after transplantation. In addition to vomiting, the patient had a fever (from day 26) and severe headache (from day 34). His cerebrospinal fluid (CSF) (day 41) demonstrated pleocytosis with an absence of leukemic cells. Although the patient's symptoms were resolved with further supportive care, abrupt onset of bilateral decreased vision occurred at day 54. He was diagnosed with bilateral optic neuritis, due to the presence of disc edema and redness. Concomitant with the occurrence of aseptic meningitis, the human herpesvirus 7 (HHV‐7) antibody titer increased significantly in this patient. Although neither HHV‐6 nor cytomegalovirus (CMV) DNA was detected in CSF collected at day 41, HHV‐7 DNA was detected in the sample. Viral DNA was not detected in CSF collected at day 93. J. Med. Virol. 70:440–443, 2003. © 2003 Wiley‐Liss, Inc.
Interaction of human herpesvirus 6 with human CD34 positive cells
Authors: Isomura Hiroki , Yoshida Mariko , Namba Hikaru , Yamada Masao
Published: May 2003

We reported previously that human herpesvirus 6 (HHV‐6) suppresses hematopoietic colony formation of erythroid (BFU‐E), granulocyte/macrophage (CFU‐GM), and megakaryocyte (CFU‐Meg) lineages in vitro. Here we describe the interaction between HHV‐6 and human CD34+ cells, which are a major source of hematopoietic progenitor cells. CD34+ cells were immunomagnetically isolated from cord blood mononuclear cells using anti‐CD34+ antibodies coated onto either Dynabeads™ or MACS beads. The CD34+ population selected with Dynabeads showed a broad range of fluorescence. The population selected with MACS beads showed a narrow range of fluorescence. After infection with HHV‐6, two transcripts of the immediate early genes were detected with both cell populations. HHV‐6 suppressed colony formation of BFU‐E, CFU‐GM, and CFU‐Meg. HHV‐6 suppressed cell growth after 3 to 7 days culture in the presence of thrombopoietin (TPO). More differentiated CD34+ cells were more susceptible to the effects of HHV‐6. These data indicate that the targets for hematopoietic suppression by HHV‐6 are the differentiated cells. J. Med. Virol. 70:444–450, 2003. © 2003 Wiley‐Liss, Inc.
Human herpesvirus‐6 modulates RANTES production in primary human endothelial cell cultures
Authors: Caruso Arnaldo , Favilli Flavia , Rotola Antonella , Comar Manola , Horejsh Douglas , Alessandri Giulio , Grassi Manuela , Di Luca Dario , Fiorentini Simona
Published: May 2003

Human herpesvirus 6 (HHV6) is a beta‐herpesvirus capable of infecting several cell types from different origins. HHV6 is the etiological agent of exantem subitum and has been associated with several diseases, all characterized by an inflammatory response triggered by chemokines. We show that strain U1102 of HHV6 is able to infect persistently human endothelial cells obtained from umbilical veins, adult aorta and adult heart microvessels, without apparent cytopathic effect. Analysis by in situ PCR showed that HHV6 sequences were present in 20% of HUVEC, 10% of aortic, and 1% of heart microvascular endothelial cells. Regardless of endothelial cell origin, HHV6 infection induced de novo synthesis of the RANTES CC‐chemokine. It was found, however, that microvascular endothelial cells, despite their lower susceptibility to HHV6 infection, showed the highest RANTES expression. Chemokine production occurred also in the absence of viral DNA synthesis. Furthermore, RANTES synthesis required an active viral genome, as UV‐inactivated HHV6 infection of endothelial cells did not lead to chemokine production. We investigated the expression of HHV6 U51 gene, which encodes a chemokine receptor that is already known to sequester and down modulate RANTES in epithelial cells. HHV6‐infected endothelial cells co‐expressed RANTES and U51 mRNAs starting from 12 hr up to 48 hr post‐infection. Then, RANTES transcripts disappeared whereas U51 messages continued to be expressed. In conclusion, this study highlights the major role of HHV6 in endothelial cell biology and the development of inflammatory processes. J. Med. Virol. 70:451–458, 2003. © 2003 Wiley‐Liss, Inc.
Virology of infantile chronic recurrent parotitis in Santiago de Chile
Authors: Vinagre Claudia , Martínez María José , Avendaño Luis Fidel , Landaeta Mirta , Pinto María Eugenia
Published: May 2003

Infantile chronic recurrent parotitis (ICRP) has been attributed to multiple causes, including viral infections, and therefore its treatment remains empirical. Our aim was to evaluate the involvement of respiratory and oropharyngeal viruses in acute episodes of ICRP. Seventy children were studied, 50 patients and 20 age‐matched controls, in a 2‐year follow‐up study. Saliva samples were taken from the parotid duct and analyzed by viral isolation and immunofluorescence for adenovirus (Ad), respiratory sincitial virus (RSV), parainfluenza virus (PI), influenza virus (Flu), Cytomegalovirus (CMV), and herpes simplex virus (HSV). Paired sera samples were tested by ELISA for anti‐Epstein‐Barr virus (EBV) IgG and anti‐mumps IgM and IgG. Viral infections were detected in 7/50 (14%) cases of the ICRP group: one CMV; 2 Enteroviruses isolated in human embryonic lung fibroblast cells; 1 Flu A; and 3 mumps virus. No EBV seroconversions were detected. In the control group, 2 out of the 20 children had an asymptomatic mumps positive IgM titer. Our data indicate that the main respiratory and oropharyngeal viruses are not the cause of acute episodes of ICRP in Chilean children. J. Med. Virol. 70:459–462, 2003. © 2003 Wiley‐Liss, Inc.
Molecular characterization of influenza B viruses circulating in northern Italy during the 2001–2002 epidemic season
Authors: Ansaldi Filippo , D'Agaro Pierlanfranco , de Florentiis Daniela , Puzelli Simona , Lin Yi Pu , Gregory Victoria , Bennett Michael , Donatelli Isabella , Gasparini Roberto , Crovari Pietro , Hay Alan , Campello Cesare
Published: May 2003

During the 2001–2002 influenza season, virological surveillance highlighted the predominant circulation of B viruses (86% of isolates) in Italy, in contrast to many other countries in Europe and North America where AH3N2 viruses were isolated most frequently, and in contrast to the infrequent isolation of B viruses in Italy during the previous two years. Associated with this predominance of influenza B was the re‐emergence of B/Victoria/2/87‐lineage viruses, closely related to B viruses prevalent during the 1980s, which are distinct antigenically and genetically from circulating B/Sichuan/379/99‐like viruses of the B/Yamagata/16/88 lineage, which predominated in most parts of the world during the last 10 years. Ninety‐four viruses isolated in two regions of northern Italy were characterized, 50 by direct sequencing of haemagglutinin (HA). Viruses of both Victoria and Yamagata lineages co‐circulated throughout the 12 weeks of the influenza season. The HAs of the Yamagata‐lineage viruses were heterogeneous and comprised two sublineages, represented by B/Sichuan/379/99 and B/Harbin/7/94, whereas the Victoria‐lineage viruses were more homogeneous and closely related to B/Hong Kong/330/01, the current prototype vaccine strain. The antigenic and genetic characteristics of the viruses correlated with certain epidemiological features. In particular, the low age (<14 years) of individuals infected with B/Hong Kong/330/01‐like viruses is likely to reflect the greater susceptibility of the youngest cohort, due to lack of previous exposure to Victoria‐lineage viruses, and is consistent with the conclusion that vaccination with a B/Sichuan/379/99‐like virus would give poor protection against infection with B/Hong Kong/330/01‐like (Victoria‐lineage) viruses. J. Med. Virol. 70:463–469, 2003. © 2003 Wiley‐Liss, Inc.
Manganese superoxide dismutase induction during measles virus infection
Authors: Wang Michael , Howell Joseph M. , Libbey Jane E. , Tainer John A. , Fujinami Robert S.
Published: May 2003

Measles virus infection of B‐cells results in marked alterations in proliferation and immunoglobulin production. Very little is known about the changes of gene expression, if any, during acute measles virus infection. To elucidate cellular genes that are induced during measles virus infection, we carried out a subtraction technique, representational differential analysis. The mitochondrial protein, manganese superoxide dismutase (MnSOD), was upregulated in B‐cells during measles virus infection. Although measles virus‐infected B‐cells did not secrete MnSOD into the environment, it was found, using an MnSOD mimetic, that intracellular MnSOD did inhibit proliferation of the B‐cells. MnSOD also decreases the titer of virus produced from infected cells. Therefore, MnSOD seems to play a role in the alteration of immune function seen upon infection of B‐cells with measles virus. J. Med. Virol. 70:470–474, 2003. © 2003 Wiley‐Liss, Inc.
Ex vivo cytokine responses against parvovirus B19 antigens in previously infected pregnant women
Authors: Corcoran Amanda , Mahon Bernard P. , McParland Peter , Davoren Anne , Doyle Sean
Published: May 2003

Parvovirus B19 infection is a significant cause of fetal death. The aim of this study was to investigate the role of maternal immune status in modulating susceptibility to fetal B19 infection. Peripheral blood was obtained from pregnant women (n = 199) with no clinical evidence of recent B19 infection. Evaluation of ex vivo T cell responses from 149/199 individuals showed significantly higher interferon‐γ levels for seropositive individuals following VP1 (268 ± 36 versus 103 ± 19 pg/ml; P = 0.003) and VP2 (242 ± 42 versus 91 ± 16 pg/ml; P = 0.01) antigen stimulation. Significantly higher levels of interleukin‐2 were also observed in seropositive individuals following both VP1 (P = 0.0003) and VP2 (P = 0.0005) stimulation. The observed Th1 cellular response is lower than that documented previously for non‐pregnant individuals and strongly suggests that diminution of the maternal anti‐viral immune response may increase susceptibility to fetal B19 infection. J. Med. Virol. 70:475–480, 2003. © 2003 Wiley‐Liss, Inc.