bluuebunny/crossref_metadata_2025 huggingface dataset:
Immunoglobulin GM and KM genotypes in hepatitis C virus infection
Authors: Vejbaesya Sasijit , Tanwandee Taweesak , Pandey Janardan P.
Published: May 2004

Hepatitis C virus (HCV) is a major health problem, affecting over 170 million people worldwide. HCV causes a wide spectrum of liver disease, varying from persistent to asymptomatic infection. To evaluate the role of immunoglobulin (Ig) GM and KM genes in HCV infection, 191 HCV‐infected Thai subjects were studied. These included 43 individuals with transient HCV infection and 148 individuals with persistent chronic HCV infection. The controls consisted of 134 healthy individuals. Several GM and KM alleles were determined by polymerase chain reaction‐based methods. The frequency of G1M(f) homozygotes was lower (52.4% vs. 64.2%, P = 0.03) and the frequency of G1M(z) homozygotes was higher (10.5% vs. 3.7%, P = 0.02) in patients than the respective frequencies in controls. These results suggest that GM genotypes make a significant contribution to the risk of acquiring HCV infection. J. Med. Virol. 73:384–386, 2004. © 2004 Wiley‐Liss, Inc.
Evaluation of a total hepatitis C virus (HCV) core antigen assay for the detection of antigenaemia in anti‐HCV positive individuals
Authors: Valcavi Pierpaolo , Medici Maria Cristina , Casula Francesca , Arcangeletti Maria Cristina , De Conto Flora , Pinardi Federica , Calderaro Adriana , Chezzi Carlo , Dettori Giuseppe
Published: May 2004

A new, sensitive enzyme immunoassay has been developed for detecting and quantifying total hepatitis C virus (HCV) core antigen in anti‐HCV positive or negative sera (“trak‐C™”, Ortho Clinical Diagnostics, Raritan, NJ). The purpose of this study was to evaluate the performance of trak‐C as an additional laboratory diagnostic marker of viraemia. The performance was compared to HCV‐RNA detection in the “screening” of sera from a large heterogeneous population of hospitalised patients and outpatients. Six hundred and eighteen anti‐HCV negative sera, 405 anti‐HCV positive/HCV‐RNA negative sera, 604 anti‐HCV positive/HCV‐RNA positive sera and 67 anti‐HCV negative sera containing antigens or antibodies potentially interfering with the performance of the assay were analysed. Supplemental HCV antibody testing was performed using a commercial strip immunoblot assay. HCV‐RNA was investigated using a qualitative commercial assay. A quantitative commercial RT‐PCR was used for the analysis of selected samples. Sensitivity and specificity values were 94.7 and 100%, respectively. The latter was also confirmed when anti‐HCV negative samples containing potentially interfering antigens/antibodies were examined. Sensitivity below 100% was probably due to an antigenaemia below the detection limit of trak‐C. Besides, because 65.6% of HCV‐RNA positive/trak‐C negative samples presented specific antibodies against all four RIBA antigens, the hypothesis was raised that, in some cases, the dissociation step efficiency could be sub‐optimal. In conclusion, trak‐C seems suitable for identifying HCV infection on large based populations. It is a rapid to perform, reliable and specific assay that can be adapted to any laboratory setting. J. Med. Virol. 73:397–403, 2004. © 2004 Wiley‐Liss, Inc.
Genetic analysis of crimean‐congo hemorrhagic fever virus in Iran
Authors: Chinikar Sadegh , Persson Stine‐Mari , Johansson Marie , Bladh Linda , Goya Mehdi , Houshmand Badakhshan , Mirazimi Ali , Plyusnin Alexander , Lundkvist Åke , Nilsson Mikael
Published: May 2004

Crimean‐Congo hemorrhagic fever (CCHF) is a potentially fatal disease caused by a tick‐borne virus in the family Bunyavridae. The disease occurs in parts of Africa, Asia, Middle East, and Eastern Europe. During recent years, an increasing number of human CCHF cases have been diagnosed in Iran, but very little information is available on the prevalence and genetic diversity of CCHFV in Iran. In the present study, CCHF virus (CCHFV) isolates from nine Iranian patients infected during 2002 were examined genetically. Nucleotide sequencing of the S‐ and M‐segments, encoding the nucleocapsid protein (NP) and the glycoproteins, respectively, revealed that the different isolates were related closely to each other with nucleotide sequence identities exceeding 98% for both S‐ and M‐segments. Phylogenetic analysis of partial S‐segment nucleotide sequences showed that the viruses clustered along with strains from Pakistan and Madagascar in one distinct lineage. Phylogenetic analysis also demonstrated that the Iranian isolates examined in this study and the previously published CCHFV strain ArTeh193‐3 clustered into different genetic groups, indicating that at least two genetic lineages of CCHFV could be co‐circulating in Iran. J. Med. Virol. 73:404–411, 2004. © 2004 Wiley‐Liss, Inc.
Lymphocyte activation and hepatic cellular infiltration in immunocompetent mice infected by dengue virus
Authors: Chen Hsuen‐Chin , Lai Show‐Yun , Sung Jui‐Min , Lee Shu‐Hwae , Lin Yu‐Chin , Wang Wei‐Kung , Chen Yee‐Chun , Kao Chuan‐Liang , King Chwan‐Chuen , Wu‐Hsieh Betty A.
Published: May 2004

Activation and expansion of dengue virus‐specific T cells and abnormal liver functions in dengue patients have been documented. However, it remains to be determined whether T cells are involved in the pathogenic mechanism of dengue virus infection. In this study, immunocompetent C57BL/6 mice were employed to study dengue virus‐induced T cell activation. Mice were inoculated with 108 PFU dengue virus serotype 2 strain 16681 by the intravenous route. Dengue viral core RNA was detected by RT‐PCR in mouse serum, liver, spleen, and brain at different time points after infection. Splenic T cells were activated as evidenced by their expression of CD69 and O‐glycosylated CD43 at as early as day 3 after infection. Splenic T cell expression of O‐glycosylated CD43 and IFN‐γ production coordinately peaked at day 5. Coincided with the peak of splenic T cell activation was hepatic lymphocyte infiltration and elevation of liver enzymes. Flow cytometric analysis revealed the infiltrating CD8+ T cell to CD4+ T cell ratio was 5/3. After a second inoculation of dengue virus, hepatic T cell infiltration and liver enzyme levels increased sharply. The infiltrating hepatic CD8+ T cell to CD4+ T cell ratio increased to 5.8/1. A strong correlation was found between T cell activation and hepatic cellular infiltration in immunocompetent mice infected with dengue virus. The kinetics of liver enzyme elevation also correlated with that of T cell activation. These data suggest a relationship between T cell infiltration and elevation of liver enzymes. J. Med. Virol. 73:419–431, 2004. © 2004 Wiley‐Liss, Inc.
Epstein–barr virus (EBV) infection and expression of the interleukin‐12 family member EBV‐induced gene 3 (EBI3) in chronic inflammatory bowel disease
Authors: Gehlert Thomas , Devergne Odile , Niedobitek Gerald
Published: May 2004

Herpesviruses have been suggested as possible etiological agents of ulcerative colitis and Crohn's disease. Recently, increased numbers of Epstein–Barr virus (EBV)‐infected cells have been detected in ulcerative colitis as compared to Crohn's disease. Interestingly, expression levels of the EBV‐induced gene 3 (EBI3), a molecule belonging to the interleukin (IL)‐12 family, have also been reported to be elevated in ulcerative colitis as compared to Crohn's disease. To test the hypothesis that these observations might be interrelated, ileocolic resection specimens were examined from 16 patients with ulcerative colitis and from 20 patients with Crohn's disease. The presence of EBV‐infected cells and of EBI3‐expressing cells was determined quantitatively by in situ hybridisation and immunohistochemistry, respectively. Larger number of EBV‐infected cells were seen in areas of active inflammation of ulcerative colitis and Crohn's disease as compared to areas of inactive inflammation. However, there was no statistically significant difference between ulcerative colitis and Crohn's disease. Numbers of EBI3‐expressing cells were increased in areas of active inflammation of ulcerative colitis and Crohn's disease but again there was no statistically significant difference between the two diseases. Double labelling experiments showed that EBI3 expression occurred only in a small minority of EBV‐infected cells in ulcerative colitis and Crohn's disease. These results suggest that increased numbers of EBV‐infected cells in areas of active inflammatory bowel disease (IBD) are secondary to influx or local proliferation of inflammatory cells and do not contribute significantly to local production of EBI3. Assessment of the possible role of EBI3 of the pathogenesis of ulcerative colitis or Crohn's disease requires information regarding the expression of other IL‐12 family members. J. Med. Virol. 73:432–438, 2004. © 2004 Wiley‐Liss, Inc.
Diversity of enteric viruses detected in patients with gastroenteritis in a tertiary referral paediatric hospital
Authors: Gallimore Chris I. , Cubitt David W. , Richards Alison F. , Gray Jim J.
Published: May 2004

The genetic diversity of enteric viruses co‐circulating in a cohort of patients with viral gastroenteritis in a large tertiary paediatric hospital in London, UK, was determined. Multiple strains of noroviruses (NV), sapoviruses (SV) and astroviruses (HAsV) were detected in these patients, indicating the likelihood of multiple introductions from different sources, possible sub‐clinical infections and simultaneous infection with different viruses in immunocompromised and other patients. Routine screening of immunocompromised patients and infection control procedures are important to prevent nosocomial infection. J. Med. Virol. 73:443–449, 2004. © 2004 Wiley‐Liss, Inc.
An outbreak of gastroenteritis during school trip caused by serotype G2 group A rotavirus
Authors: Mikami Toshiyuki , Nakagomi Toyoko , Tsutsui Rika , Ishikawa Kazuko , Onodera Yohko , Arisawa Kokichi , Nakagomi Osamu
Published: May 2004

Between May14 and 18, 2001, there was an outbreak of acute gastroenteritis involving 45 school children out of a total of 107 (aged 11–12 years) attending a 3‐day school trip. The epidemic curve characterized by a rapid onset and decline with a single peak incidence over a 5‐day period resembled the pattern typical of a food‐borne gastroenteritis outbreak. Epidemiological and virological investigations concluded, however, that this outbreak was caused by a single strain of serotype G2 group A rotavirus spreading to schoolmates from the primary case‐pupil who had already been ill at the start of the trip. Efficient person‐to‐person transmission was likely to have occurred due to prolonged and close contacts under the conditions typical of such school trips. This study emphasizes the importance of including group A rotavirus infection as a possible cause of gastroenteritis outbreaks even in older children and adults. J. Med. Virol. 73:460–464, 2004. © 2004 Wiley‐Liss, Inc.
Human herpesvirus 6 (HHV‐6) is transmitted from parent to child in an integrated form and characterization of cases with chromosomally integrated HHV‐6 DNA
Authors: Tanaka‐Taya Keiko , Sashihara Junji , Kurahashi Hiroki , Amo Kiyoko , Miyagawa Hiromi , Kondo Kazuhiro , Okada Shintaro , Yamanishi Koichi
Published: May 2004

We obtained 7,566 peripheral blood mononuclear cell (PBMC) samples from 2,332 individuals and screened them for human herpesvirus infection. We identified five individuals who persistently harbored high copy numbers of human herpesvirus 6 (HHV‐6) DNA in their PBMCs. HHV‐6 DNA was also detected in other somatic tissues of these individuals. Five additional cases were identified among their family members. For two of these families, chromosomally integrated HHV‐6 DNA (CIHHV‐6) was detected in the PBMCs by fluorescence in situ hybridization. The prevalence of CIHHV‐6 among all the subjects was 0.21%. The HHV‐6 DNA was variant B in four families and variant A in one family. Antibodies to immediate early antigen and glycoprotein B were detected in 57 and 14% of individuals with CIHHV‐6 and in 0 and 60% of healthy volunteers without CIHHV‐6, respectively. HHV‐6 could not be isolated from PBMCs with CIHHV‐6. These cases shared no clinical features, and included three healthy individuals. Our data suggest that CIHHV‐6 is rare but detectable in the general population and that hereditary transmission is one of the routes of HHV‐6 transmission. J. Med. Virol. 73:465–473, 2004. © 2004 Wiley‐Liss, Inc.
Human papillomavirus in a rural community in Zimbabwe: The impact of HIV co‐infection on HPV genotype distribution
Authors: Baay Marc F.D. , Kjetland Eyrun F. , Ndhlovu Patricia D. , Deschoolmeester Vanessa , Mduluza Takafira , Gomo Exenevia , Friis Henrik , Midzi Nicholas , Gwanzura Lovemore , Mason Peter R. , Vermorken Jan B. , Gundersen Svein G.
Published: May 2004

Cervical cancer is a leading cause of cancer‐related deaths in developing countries, and the human papillomavirus (HPV) is linked etiologically to cervical cancer. Hence, a vaccine which prevents HPV‐associated cervical cancer would have the most impact in developing countries, including the African continent. The type‐specific immune response towards HPV virus‐like particles, in combination with geographical variation in the prevalence of HPV, necessitates the presence of multiple HPV type antigens in a single vaccine cocktail in order to provide relevant protection. We aimed to investigate whether co‐infection with HIV, which is highly prevalent in Africa, plays a role in HPV genotype distribution. After informed consent, HPV detection by GP5+/6+ PCR and HIV detection by serology was carried out on 236 women from the rural north‐western part of Zimbabwe. The prevalence of HPV was higher in HIV positive women (54%) than in HIV negative women (27%). Certain HPV types (HPV types 11, 39, 43, 51, and 59, P‐values ranging from 0.017 to 0.067) occurred more frequently in HIV positive women. Only high‐risk HPV, and not HIV, was associated significantly with cervical intraepithelial neoplasia in multiple regression analysis. In conclusion, a high prevalence of HPV was found in a rural community, where regular Papanicolaou (Pap) smears would be a logistic and economic impossibility, but where free vaccination programmes against other infections are already established. The results suggest that HIV co‐infection may have an impact on HPV genotype distribution. J. Med. Virol. 73:481–485, 2004. © 2004 Wiley‐Liss, Inc.
Human metapneumovirus infection in hospital referred South African children
Authors: IJpma Frank F.A. , Beekhuis Dennis , Cotton Mark F. , Pieper Clarissa H. , Kimpen Jan L.L. , van den Hoogen Bernadette G. , van Doornum Gerard J.J. , Osterhaus D.M.E.
Published: May 2004

Human metapneumovirus (hMPV) was first described in Dutch children with acute respiratory symptoms. A prospective analysis of the epidemiology, clinical manifestation, and seroprevalence of hMPV and other respiratory viruses in South African children referred to hospital for upper or lower respiratory tract infection were carried out during a single winter season, by using RT‐PCR, viral culture, and enzyme‐linked immunosorbent assays. In nasopharyngeal aspirates from 137 children, hMPV was detected by RT‐PCR in 8 (5.8%) children (2–43 months of age) as a sole viral pathogen, respiratory syncytial virus (RSV) in 21 (15%), influenza A virus in 18 (13%) and influenza B virus in 20 (15%). Pneumonia was diagnosed in seven children and upper respiratory tract infection in one of the hMPV‐infected children. One hMPV‐infected child was admitted to the intensive care unit in need of mechanical ventilation and one child was infected with human immunodeficiency virus (HIV). No statistically significant differences were found between hMPV, RSV, and influenza virus infected groups with regard to clinical signs and symptoms and chest radiograph findings. The seropositive rate of hMPV specific IgG antibodies was 92% in children aged 24–36 months, the oldest seronegative child in our study was 7 years and 6 months of age. In conclusion, hMPV contributes to upper and lower respiratory tract morbidity in South African children. J. Med. Virol. 73:486–493, 2004. © 2004 Wiley‐Liss, Inc.
The stationarity of global mean climate
Authors: Hunt B. G.
Published: May 2004

The observed climate exhibits noticeable fluctuations on a range of temporal and spatial scales. Major fluctuations are often attributed to ‘external’ influences, such as volcanic eruptions or solar perturbations, which obscure climatic fluctuations associated with natural climatic variability generated by internal processes within the climatic system. Although it is difficult to isolate the role of natural climatic variability within the observed climatic system, coupled global climatic models permit such a discrimination to be made in appropriately designed simulations. Thus, the CSIRO coupled global climatic model has been used to determined some basic characteristics of annually averaged global mean climate within a multi‐millennial climatic simulation. Some examination of observed climate is also presented. A stationary climatic state was simulated for periods of up to 10 000 years using the CSIRO model, with equilibrium usually being maintained to within 1–2% for all climatic variables investigated.

The means by which such stationarity is maintained is analysed and the necessity for rapid negative feedback mechanisms is emphasized. The role of topographically induced climatic features is also discussed. Finally, the implications of the present, presumably greenhouse‐related, global warming are considered in the context of the present results. Copyright © 2004 Royal Meteorological Society
Trend analysis of precipitation and drought in Basilicata from 1923 to 2000 within a southern Italy context
Authors: Piccarreta Marco , Capolongo Domenico , Boenzi Federico
Published: May 2004

Series of annual, monthly and seasonal precipitation from 50 stations, distributed all over the Basilicata territory (southern Italy), were studied for the period 1923–2000. All the series were checked for homogeneity using MASH v. 1.0.1 software and the time series analysis was performed with the Mann–Kendall nonparametric test in order to detect possible trends. The results show that the annual total rainfall decreased by about 156 mm during the period investigated; the decrease becomes stronger in the last 30 years. There are considerably different trends for the different seasons. In particular, only the winter trend, which is downward, is statistically significant. In this season the total rainfall has decreased by about 133 mm. For this same period the standardized precipitation index (SPI) for multiple time scales of 12, 24 and 48 months has been computed. It appears that periods of drought have been quite frequent starting from 1975, with SPI ranging from about −1 to about −3. Copyright © 2004 Royal Meteorological Society
Self‐Initiated Photopolymerization and Photografting of Acrylic Monomers
Authors: Wang Huiliang , Brown Hugh R.
Published: May 2004

Summary: This work demonstrates that acrylic acid (AA), glycidyl acrylate (GA) and several other acrylic monomers can be photopolymerized and photografted onto high‐density polyethylene (HDPE) by self‐initiation. The self‐initiation mechanism of these acrylic monomers is possibly by an excitation of the monomer to a triplet state (T3) with enough energy to abstract hydrogen from the polymer substrate and initiate the grafting.

Grafting conversion of acrylic acid (AA), methacrylic acid (MAA), 2‐hydroxyethyl acrylate (HEA), glycidyl acrylate (GA), 2‐hydroxyethyl methacrylate (HEMA) and poly(ethylene glycol) methacrylate (PEGMA) as a function of irradiation time.

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Grafting conversion of acrylic acid (AA), methacrylic acid (MAA), 2‐hydroxyethyl acrylate (HEA), glycidyl acrylate (GA), 2‐hydroxyethyl methacrylate (HEMA) and poly(ethylene glycol) methacrylate (PEGMA) as a function of irradiation time.
Effect of Shear Flow on the Polymeric Gels Formed by Macroscopic Phase Separation
Authors: Park Moon Jeong , Char Kookheon
Published: May 2004

Summary: Shear‐induced phase behavior of poly(ethylene oxide‐b‐(DL‐lactic acid‐co‐glycolic acid)‐b‐ethylene oxide) (PEO‐PLGA‐PEO) triblock copolymers in water is investigated using rheology and small‐angle neutron scattering equipped with an in situ Couette shear cell. For gels formed by the macroscopic phase separation, the steady shear experiment reveals that the flow‐induced anisotropy on a nanometer length scale at a critical shear rate and the phase separation on a larger length scale are successively induced with a further increase in the shear rate. In particular, the hard gels show a memory effect inscribed by a pre‐high shear in contrast to the soft gels.

2D SANS patterns clearly show the memory effect of the hard gels at a pre‐high shear.

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2D SANS patterns clearly show the memory effect of the hard gels at a pre‐high shear.
Elevated expression of TGF‐β1 in head and neck cancer–associated fibroblasts
Authors: Rosenthal Eben , McCrory Allison , Talbert Melissa , Young Geoff , Murphy‐Ullrich Joanne , Gladson Candece
Published: May 2004

Head and neck cancers are characterized by a vigorous desmoplastic response, but the contribution of stromal‐derived growth factors to the tumor microenvironment is poorly understood. We evaluated the expression of stromal growth factor expression in head and neck squamous cell carcinoma (HNSCC) in normal and tumor‐associated stromal cells. Stromal tissue was isolated from epithelial cells with laser capture microdissection (LCMD) and analyzed by cDNA array for the expression of TGFα, TGF‐β1, HGF, PDGF‐α, IGFII, bFGF, aFGF, VEGFC, and VEGF. Primary fibroblasts were isolated in vitro from HNSCC tumors, adjacent histologically normal mucosa, and skin in vitro. Fibroblast populations were assessed for TGF‐β1 expression by ELISA and luciferase reporter assay to assess protein expression. We identified TGF‐β1 and IGFII overexpression in normal and tumor‐associated stromal cells; however, only TGF‐β1 was significantly overexpressed (3.4‐fold) in tumor‐associated stroma. Assessment of carcinoma‐associated fibroblasts (CAFs), normal dermal fibroblasts (NDFs), and normal mucosal fibroblasts (NMFs) in propagated fibroblasts demonstrated persistently elevated levels of TGF‐β1 in CAFs compared to NMF and NDF populations. Elevated levels of TGF‐β1 were identified in the stromal compartment of HNSCC tumors compared to normal mucosa by immunohistochemical analysis. These results suggest that TGF‐β1 mRNA and protein is specifically upregulated in CAFs in vitro and in vivo. © 2004 Wiley‐Liss, Inc.
Mutation frequencies in murine keratinocytes as a function of carcinogenic status
Authors: Christensen Laura A. , Conti Claudio J. , Fischer Susan M. , Vasquez Karen M.
Published: May 2004

A link between genetic abnormalities and carcinogenesis is well established. It follows that a correlation exists between mutation frequency and malignant progression. We have determined the spontaneous and DNA damage–induced mutation frequencies for a series of cell lines derived from SENCAR mouse keratinocytes at various stages of malignant progression. Nontumorigenic mouse keratinocytes (3PC), papillomas (MT1/2), squamous‐cell carcinomas (CH72), and spindle‐cell carcinomas (CH72T4) were transfected with damaged or undamaged shuttle vectors containing a supF mutation reporter gene. The plasmid mutation frequencies were determined by blue/white screening. The spontaneous plasmid mutation frequency of the squamous‐cell carcinoma line was slightly higher than the mutation frequencies of the other cell lines tested. The DNA damage induced by triplex‐directed psoralen crosslinks increased the mutation frequencies sixfold to eighteenfold in all cell lines tested, with no significant differences among the cell lines. Sequence analyses revealed that the spindle‐cell carcinoma line had a different spontaneous mutation spectrum from the other cell lines. DNA damage–induced mutations were predominantly point mutations at the triplex‐duplex junction in all of the cell lines tested, as expected. These data suggested that a strong mutator phenotype was not required for progression to an advanced malignant phenotype in our model system. © 2004 Wiley‐Liss, Inc.
Dihydroagarofurans: the fourth isomer isolated from Cedrelopsis grevei bark oil
Authors: Cavalli Jean‐François , Tomi Félix , Bernardini Antoine‐François , Casanova Joseph
Published: May 2004

4‐Epi‐cis‐dihydroagarofuran was isolated from the bark oil of Cedrelopsis grevei and its structure was elucidated by 1D and 2D‐NMR spectroscopy. Copyright © 2004 John Wiley & Sons, Ltd.
Non‐empirical calculations of NMR indirect carbon–carbon coupling constants. Part 8—Monocycloalkanes
Authors: Sauer Stephan P. A. , Krivdin Leonid B.
Published: May 2004

Carbon–carbon and carbon–hydrogen spin–spin coupling constants were calculated in the series of the first six monocycloalkanes using SOPPA and SOPPA(CCSD) methods, and very good agreement with the available experimental data was achieved, with the latter method showing slightly better results in most cases, at least in those involving calculations of J(C,C). Benchmark calculations of all possible 21 coupling constants J(C,C), J(C,H) and J(H,H) in chair cyclohexane revealed the importance of using the appropriate level of theory and adequate quality of the basis sets. Many unknown couplings in this series were predicted with high confidence and several interesting structural trends (hybridization effects, multipath coupling transmission mechanisms, hyperconjugative interactions) were elucidated and are discussed based on the present calculations of spin–spin couplings. Copyright © 2004 John Wiley & Sons, Ltd.
In vivo 1H MRS of brain injury and repair during acute SIV infection in the macaque model of neuroAIDS
Authors: Greco Jane B. , Westmoreland Susan V. , Ratai Eva M. , Lentz Margaret R. , Sakaie Ken , He Julian , Sehgal Prabhat K. , Masliah Eliezer , Lackner Andrew A. , González R. Gilberto
Published: May 2004

The metabolic response of the rhesus macaque brain during acute simian immunodeficiency virus (SIV) infection was investigated with in vivo 1H MR spectroscopy. Fifteen rhesus macaques were studied before inoculation, and once or twice after infection. In all, 13/15 macaques had elevations of Cho/NAA at 11–13 days postinoculation (dpi); all 10 macaques measured after 13 dpi had subsequent reduction of this ratio (ANOVA, P < 10‐6). There were significant increases in Cho/Cr (20%, P = 0.04) and MI/Cr (14%, P = 0.003) at 11 dpi. At 13 dpi a 7.7% decrease (P = 0.02) in NAA/Cr was observed, while Cho/Cr was no longer significantly different from baseline. At 27 dpi Cho/Cr was decreased to 18% (P = 0.004) below preinoculation values, while NAA/Cr and MI/Cr were at baseline values. Absolute concentrations of Cho, MI, and NAA showed a similar time course, with no observed changes in Cr. There was a strong correlation between Cho/Cr change and plasma viral load (rs = 0.79, P < 0.01). Acute SIV produces extensive metabolic abnormalities in the brain, which may reflect inflammation and neuronal injury, which are reversed with immunological control of the virus. Similar events are likely to occur in acutely HIV‐infected people, and may explain the neurobehavioral symptoms associated with acute HIV infection. Magn Reson Med 51:1108–1114, 2004. © 2004 Wiley‐Liss, Inc.
In vivo monitoring of tissue pharmacokinetics of liposome/drug using MRI: Illustration of targeted delivery
Authors: Viglianti Benjamin L. , Abraham Sheela A. , Michelich Charles R. , Yarmolenko Pavel S. , MacFall James R. , Bally Marcel B. , Dewhirst Mark W.
Published: May 2004

The purpose of this study was to determine if MnSO4/doxorubicin (DOX) loaded liposomes could be used for in vivo monitoring of liposome concentration distribution and drug release using MRI. In vitro results show that T1 shortening correlates with MnSO4 concentration. Using a temperature‐sensitive liposome formulation, it was found that MnSO4 release significantly shortened T1. This feature, therefore, suggests that content release can also be measured with these MnSO4‐loaded liposomes. The feasibility of monitoring this drug delivery and release‐imaging agent was shown in a murine tumor model. Upon tumor heating, nonthermally sensitive liposomes selectively but heterogeneously accumulated in the tumor region. The thermally sensitive liposomes showed a clear pattern of accumulation at the periphery of the tumor, concordant with the release temperature of this formulation (39–40°C). This liposome contrast agent has potential for use with hyperthermia by providing individualized monitoring of tissue drug concentration distribution during or after treatment. This would allow for: 1) modification of treatment variables to improve the uniformity of drug delivery, and 2) provide a means to select patients most likely to benefit from this liposomal drug treatment. Additionally, the drug‐loading method used for this liposome is applicable to a wide range of drugs, thereby broadening its applicability. The method is also applicable to other liposomal formulations with triggered release mechanisms. Magn Reson Med 51:1153–1162, 2004. © 2004 Wiley‐Liss, Inc.
Carbon blacks as EPR sensors for localized measurements of tissue oxygenation
Authors: Lan Minbo , Beghein Nelson , Charlier Nicolas , Gallez Bernard
Published: May 2004

New electron paramagnetic resonance (EPR) oximetry probes were identified in the class of carbon black materials. These compounds exhibit very high oxygen sensitivity and favorable EPR characteristics for biological applications. At low pO2, the linewidth is particularly sensitive to changes in oxygen tension (sensitivity of 750 mG/mmHg). The application of the probes for oximetry was demonstrated in vivo: the pO2 was measured in muscle in which the blood flow was temporarily restricted as well as in tumor‐bearing mice during a carbogen breathing challenge. The responsiveness to pO2 was stable in muscle for at least 3 months. No toxicity was observed using these materials in cellular experiments and in histological studies performed 2, 7, and 28 days after implantation. In view of their EPR characteristics (high sensitivity) as well as the well‐characterized production procedure that make them available on a large scale, these probes can be considered as very promising tools for future developments in EPR oximetry. Magn Reson Med 51:1272–1278, 2004. © 2004 Wiley‐Liss, Inc.
Dynamic field map estimation using a spiral‐in/spiral‐out acquisition
Authors: Sutton Bradley P. , Noll Douglas C. , Fessler Jeffrey A.
Published: May 2004

The long readout times of single‐shot acquisitions and the high field strengths desired for functional MRI (fMRI) using blood oxygenation level‐dependent (BOLD) contrast make functional scans sensitive to magnetic field inhomogeneity. If it is not corrected during image reconstruction, field inhomogeneity can cause geometric distortions in the images when Cartesiank‐space trajectories are used or blurring with spiral acquisitions. Many traditional methods to correct for field inhomogeneity distortions rely on a static field map measured with the use of images that are themselves distorted. In this work, we employ a regularized least‐squares approach to jointly estimate both the undistorted image and field map at each acquisition using a spiral‐in/spiral‐out pulse sequence. Simulation and phantom studies show that this method is accurate and stable over a time series. Human functional studies show that the jointly estimated field map may be more accurate than standard field map estimates in the presence of respiration‐induced phase oscillations, leading to better detection of functional activation. The proposed method measures a dynamic field map that accurately tracks magnetic field drift and respiration‐induced phase oscillations during the course of a functional study. Magn Reson Med 51:1194–1204, 2004. © 2004 Wiley‐Liss, Inc.
Efficiency of flow‐driven adiabatic spin inversion under realistic experimental conditions: A computer simulation
Authors: Trampel Robert , Jochimsen Thies H. , Mildner Toralf , Norris David G. , Möller Harald E.
Published: May 2004

Continuous arterial spin labeling (CASL) using adiabatic inversion is a widely used approach for perfusion imaging. For the quantification of perfusion, a reliable determination of the labeling efficiency is required. A numerical method for predicting the labeling efficiency in CASL experiments under various experimental conditions, including spin relaxation, is demonstrated. The approach is especially useful in the case of labeling at the carotid artery with a surface coil, as consideration of the experimental or theoretical profile of the B1 field is straightforward. Other effects that are also accounted for include deviations from a constant labeling gradient, and variations in the blood flow velocity due to the cardiac cycle. Assuming relevant experimental and physiological conditions, maximum inversion efficiencies of about 85% can be obtained. Magn Reson Med 51:1187–1193, 2004. © 2004 Wiley‐Liss, Inc.
Single‐shot two‐echo technique for simultaneous measurement of GABA and creatine in the human brain in vivo
Authors: Choi In‐Young , Lee Sang‐Pil , Merkle Hellmut , Shen Jun
Published: May 2004

A single‐shot, two‐echo method for the simultaneous detection of multiple‐quantum (MQ)‐filtered γ‐aminobutyric acid (GABA) and creatine (Cr) was developed and demonstrated in the human brain in vivo at 3 Tesla. The simultaneously measured Cr singlet served as a navigator for the spectral phase of GABA and any frequency shift during measurements due to drift in the static magnetic field (B0) or subject movement, as well as an internal concentration reference. In addition, the use of a double‐band frequency‐selective MQ filter for C3 and C4 methylene protons of GABA provided a very robust measurement of GABA, with excellent suppression of overlapping metabolites such as Cr and glutathione (GSH) in each single scan. Contamination from overlapping macromolecules was also demonstrated to be negligible with this method. The GABA‐to‐Cr ratio was 0.09 ± 0.03 (mean ± SD, N = 17) and the estimated concentration of GABA in the frontoparietal region of the human brain in vivo was 0.66 ± 0.19 μmol/g (mean ± SD, N = 17) with the internal reference method, and 0.69 ± 0.18 μmol/g (mean ± SD, N = 17) with the external reference method. The observed pattern of GABA doublet was consistent among all subjects, with a frequency separation of ∼13 Hz. Magn Reson Med 51:1115–1121, 2004. © 2004 Wiley‐Liss, Inc.
Quantitative proton magnetic resonance spectroscopy of the cervical spinal cord
Authors: Cooke F.J. , Blamire A.M. , Manners D.N. , Styles P. , Rajagopalan B.
Published: May 2004

Proton MR spectroscopy (1H‐MRS) provides indices of neuronal damage in the central nervous system (CNS); however, it has not been extensively applied in the spinal cord. This work describes an optimized proton spectroscopy protocol for examination of the human cervical spinal cord. B0 field mapping of the cord revealed periodic inhomogeneities due to susceptibility differences with surrounding tissue. By combining field maps and experimental data, we found that the optimum voxel size was 9 × 7 × 35 mm3 placed with the inferior end of the voxel above vertebral body C2. Metabolite concentrations were determined in the cervical cord in six healthy controls by short‐echo point‐resolved spectroscopy (PRESS) volume localization. The results were compared with metabolite concentrations in the brainstem, cerebellum, and cortex in the same individuals. The concentrations in the cervical cord were as follows: N‐acetyl‐aspartate (NAA) 17.3 ± 0.5, creatine (Cr) 9.5 ± 0.9, and choline 2.7 ± 0.5 mmol/l. The NAA concentration was significantly lower in the cord than in the brainstem (Mann‐Whitney, P < 0.025), and higher than in the cortex (P < 0.005) and cerebellum (P < 0.005). Cr was significantly lower in the cord than in the cerebellum (P < 0.05). There were no significant differences between Cr concentrations in the spinal cord compared to the cortex and brainstem. Magn Reson Med 51:1122–1128, 2004. © 2004 Wiley‐Liss, Inc.
Method for spatially interleaving two images to halve EPI readout times: Two reduced acquisitions interleaved (TRAIL)
Authors: Priest Andrew N. , Carmichael David W. , De Vita Enrico , Ordidge Roger J.
Published: May 2004

A new MRI method is presented that can generate images using half the normal readout time or, more usefully, half the number of phase‐encode steps, combining two readouts per excitation. However, the corresponding data are interleaved in image space—not in k‐space, as in many other fast techniques. This gives a resilience to the phase‐related artifacts that can occur in many other techniques due to subject motion. A modified stimulated‐echo experiment is used to create two low‐resolution images from a single sequence. The magnetization that contributes to these images is nonuniformly distributed within each pixel, forming two sinusoidal waves in quadrature, with an oscillation period of exactly two pixels. Since only half of each pixel contributes significant signal, the two images can be interleaved to create a full image with twice as many pixels and double the resolution. When the technique is used in the phase‐encode direction, the effective imaging time is halved, though with two readouts per TR period. When two half‐length echo‐planar readouts are used, the method can also reduce blurring and distortion by halving the effective readout time for echo‐planar imaging (EPI). For even further improvements, the technique can be combined with partial Fourier or parallel imaging. Magn Reson Med 51:1212–1222, 2004. © 2004 Wiley‐Liss, Inc.
MR‐trackable intramyocardial injection catheter
Authors: Karmarkar P.V. , Kraitchman D.L. , Izbudak I. , Hofmann L.V. , Amado L.C. , Fritzges D. , Young R. , Pittenger M. , Bulte J.W.M. , Atalar E.
Published: May 2004

There is growing interest in delivering cellular agents to infarcted myocardium to prevent postinfarction left ventricular remodeling. MRI can be effectively used to differentiate infarcted from healthy myocardium. MR‐guided delivery of cellular agents/therapeutics is appealing because the therapeutics can be precisely targeted to the desired location within the infarct. In this study, a steerable intramyocardial injection catheter that can be actively tracked under MRI was developed and tested. The components of the catheter were arranged to form a loopless RF antenna receiver coil that enabled active tracking. Feasibility studies were performed in canine and porcine myocardial infarction models. Myocardial delayed‐enhancement (MDE) imaging identified the infarcted myocardium, and real‐time MRI was used to guide left ventricular catheterization from a carotid artery approach. The distal 35 cm of the catheter was seen under MRI with a bright signal at the distal tip of the catheter. The catheter was steered into position, the distal tip was apposed against the infarct, the needle was advanced, and a bolus of MR contrast agent and tissue marker dye was injected intramyocardially, as confirmed by imaging and postmortem histology. A pilot study involving intramyocardial delivery of magnetically labeled stem cells demonstrated the utility of the active injection catheter system. Magn Reson Med 51:1163–1172, 2004. © 2004 Wiley‐Liss, Inc.
Optimized interleaved whole‐brain 3D double inversion recovery (DIR) sequence for imaging the neocortex
Authors: Boulby P.A. , Symms M.R. , Barker G.J.
Published: May 2004

For a substantial number of individuals with neurological disorders, a conventional MRI scan does not reveal any obvious etiology; however, it is believed that abnormalities in the neocortical gray matter (GM) underlie many of these disorders. Attempts to image the neocortex are hindered by its thin, convoluted structure, and the partial volume (PV) effect. Therefore, we developed a 3D version of the double inversion recovery (DIR) sequence that incorporates an optimized interleaved (OIL) strategy to improve efficiency and allow high‐quality, high‐resolution imaging of GM. Magn Reson Med 51:1181–1186, 2004. © 2004 Wiley‐Liss, Inc.
Referenceless PRF shift thermometry
Authors: Rieke Viola , Vigen Karl K. , Sommer Graham , Daniel Bruce L. , Pauly John M. , Butts Kim
Published: May 2004

The proton resonance frequency (PRF) shift provides a means of measuring temperature changes during minimally invasive thermotherapy. However, conventional PRF thermometry relies on the subtraction of baseline images, which makes it sensitive to tissue motion and frequency drift during the course of treatment. In this study, a new method is presented that eliminates these problems by estimating the background phase from each acquired image phase. In this referenceless method, a polynomial is fit to the background phase outside the heated region in a weighted least‐squares fit. Extrapolation of the polynomial to the heated region serves as the background phase estimate, which is then subtracted from the actual phase. The referenceless method is demonstrated on a phantom during laser heating, 0° temperature rise images of in vivo human liver, interstitial laser ablation of porcine liver, and transurethral ultrasound ablation of canine prostate. A good correlation between temperature maps reconstructed with the referenceless and subtraction methods was found. Magn Reson Med 51:1223–1231, 2004. © 2004 Wiley‐Liss, Inc.
Magnetic resonance electrical impedance tomography at 3 tesla field strength
Authors: Oh Suk H. , Lee Byung I. , Park Tae S. , Lee Soo Y. , Woo Eung J. , Cho Min H. , Seo Jin K. , Kwon Ohin
Published: May 2004

Magnetic resonance electrical impedance tomography (MREIT) is a recently developed imaging technique that combines MRI and electrical impedance tomography (EIT). In MREIT, cross‐sectional electrical conductivity images are reconstructed from the internal magnetic field density data produced inside an electrically conducting object when an electrical current is injected into the object. In this work we present the results of electrical conductivity imaging experiments, and performance evaluations of MREIT in terms of noise characteristics and spatial resolution. The MREIT experiment was performed with a 3.0 Tesla MRI system on a phantom with an inhomogeneous conductivity distribution. We reconstructed the conductivity images in a 128 × 128 matrix format by applying the harmonic Bz algorithm to the z‐component of the internal magnetic field density data. Since the harmonic Bz algorithm uses only a single component of the internal magnetic field data, it was not necessary to rotate the object in the MRI scan. The root mean squared (RMS) errors of the reconstructed images were between 11% and 35% when the injection current was 24 mA. Magn Reson Med 51:1292–1296, 2004. © 2004 Wiley‐Liss, Inc.
TRIM: TR independent multislice imaging
Authors: Fautz Hans‐Peter , Paul Dominik , Scheffler Klaus , Hennig Jürgen
Published: May 2004

This article introduces a novel concept to overcome the dependence of image contrast on spatial positioning parameters such as the number of slices and slice separation in multislice measurements: TR‐independent multislice (TRIM) acquisition allows the number of slices in a single measurement to remain independent of the repetition time TR. Ramped TRIM (rTRIM) allows the distance between the sections excited in each repetition to remain independent of the distance between the reconstructed slices. Even images from overlapping slices can be acquired without crosstalk between the images of adjacent slices due to spatially overlapping excitation profiles. This concept is based on a special reordering scheme: Within a single TR acquisition, steps are only taken from a fraction of all slices. This necessitates attribution of different phase‐encoding steps to different slices within each repetition cycle. The reordering scheme can be derived by the use of a design matrix. The imaging properties of the technique are discussed theoretically and illustrated by a point spread function analysis based on simulations and phantom measurements. Potential sources of artifacts are identified and methods for their prevention are developed. Optimized implementations with different T1‐weighted sequences such as spin echo (SE), turbo spin echo (TSE), and spoiled gradient echo acquisitions are shown on normal volunteers with imaging parameters used in routine diagnosis. Magn Reson Med 51:1239–1246, 2004. © 2004 Wiley‐Liss, Inc.
Improved magnetization preparation for navigator steady‐state free precession 3D coronary MR angiography
Authors: Nguyen Thanh D. , Spincemaille Pascal , Wang Yi
Published: May 2004

The purpose of this work was to investigate a new magnetization preparation scheme for navigator steady‐state free precession (SSFP) 3D coronary MR angiography (MRA) that executes the navigator and fat saturation pulses in steady state after the dummy RFs in order to minimize the delay between the magnetization preparation and the image echoes. Compared to the previous preparation scheme that executes the navigator and fat saturation pulses before the dummy RFs, the new scheme was found to provide more effective motion suppression, significantly improved blood‐to‐myocardium contrast‐to‐noise ratio (46%, P < 0.001) at slightly but insignificantly decreased blood signal‐to‐noise ratio (SNR) (2%, P = 0.73), significantly reduced fat SNR (32%, P < 0.001), and better overall image quality (P = 0.05; Wilcoxon paired sample signed rank test). Magn Reson Med 51:1297–1300, 2004. © 2004 Wiley‐Liss, Inc.
Quantitation of erythrocyte pentose pathway flux with [2‐13C]glucose and 1H NMR analysis of the lactate methyl signal
Authors: Delgado Teresa C. , Castro M. Margarida , Geraldes Carlos F. , Jones John G.
Published: May 2004

A simple and sensitive NMR method for quantifying excess 13C‐enrichment in positions 2 and 3 of lactate by 1H NMR spectroscopy of the lactate methyl signal is described. The measurement requires neither signal calibrations nor the addition of a standard and accounts for natural abundance 13C‐contributions. As a demonstration, the measurement was applied to ∼3 μmol of lactate generated by erythrocyte preparations incubated with [2‐13C]glucose to determine the fraction of glucose metabolized by the pentose phosphate pathway (PP). PP fluxes were estimated from the ratio of excess 13C‐enrichment in lactate carbon 3 relative to carbon 2 in accordance with established metabolic models. Under baseline conditions, PP flux accounted for 7 ± 2% of glucose consumption while in the presence of methylene blue, a classical activator of PP activity, its contribution increased to 27 ± 10% of total glucose consumption (P < 0.01). Magn Reson Med 51:1283–1286, 2004. © 2004 Wiley‐Liss, Inc.