bluuebunny/crossref_metadata_2025 huggingface dataset:
Accumulation of human immunodeficiency virus‐specific cytotoxic T lymphocytes away from the predominant site of virus replication during primary infection
Authors: Pantaleo Giuseppe , Soudeyns Hugo , Demarest James F. , Vaccarezza Mauro , Graziosi Cecilia , Paolucci Stefania , Daucher Marybeth , Cohen Oren J. , Denis François , Biddison William E. , Sekaly Rafick P. , Fauci Anthony S.
Published: March 2007

Down‐regulation of the initial burst of viremia during primary human immunodeficiency virus (HIV) infection is thought to be mediated predominantly by HIV‐specific CD8+ cytotoxic T lymphocytes (CTL). This response is associated with major perturbations in the T cell receptor (TCR) repertoire. To investigate the failure of the cellular immune response to adequately control viral spread and replication and to prevent establishment of HIV infection, changes in the TCR repertoire and in the distribution of virus‐specific CTL between blood and lymph node were analyzed in three patients with primary infection. By the combined use of clonotype‐specific polymerase chain reaction and analysis of the frequency of in vivo activated HIV‐specific CTL, it was shown that HIV‐specific CTL clones preferentially accumulated in blood as opposed to lymph node. Accumulation of HIV‐specific CTL in blood occurred prior to effective downregulation of virus replication in both blood and lymph node. These findings should provide new insights into how HIV, and possibly other viruses, elude the immune response of the host during primary infection.
Cloning of a mouse homolog of CD94 extends the family of C‐type lectins on murine natural killer cells
Authors: Vance Russell E. , Tanamachi Dawn M. , Hanke Thomas , Raulet David H.
Published: March 2007

Two families of major histocompatibility complex (MHC) class I‐specific receptors are found on natural killer (NK) cells: immunoglobulin‐like receptors and C‐type lectin receptors. In mice, the latter category is represented by the Ly49 family of receptors, whereas in humans, NK cells express the distantly related CD94, which forms MHC class I‐specific heterodimers with NKG2 family members. Humans also express the MHC class I‐specific p50/p58/p70 family of immunoglobulin‐like receptors, but these have not been identified in mice. Hence, there is no known instance of an MHC class I‐specific receptor that is expressed by both human and murine NK cells. Here we report the cloning of CD94 from the CB.17 and C57BL/6 strains of mice. Mouse CD94 is 54 % identical and 66 % similar to human CD94, and is also a member of the C‐type lectin superfamily. Mouse CD94 is expressed efficiently on the cell surface of cells transiently transfected with the corresponding cDNA, but surface CD94 was unable to mediate detectable binding to MHC class I‐expressing ConA blasts. Notably, mouse CD94, like human CD94, has a very short cytoplasmic tail, suggesting the existence of partner chains that may play a role in ligand binding and signaling. Like many other C‐type lectins expressed by NK cells, mouse CD94 maps to the NK complex on distal chromosome 6, synteneic to human CD94. We also demonstrate that mouse CD94 is highly expressed specifically by mouse NK cells, raising the possibility that mice, like humans, express multiple families of MHC class I‐specific receptors on their NK cells. Murine homologs of human NKG2 family members have not yet been identified, but we report here the existence of a murine NKG2D‐like sequence that also maps to the murine NK complex near CD94 and Ly49 family members.
Recruitment, activation and proliferation of CD8+ memory T cells in an immunoprivileged site
Authors: Stevenson Philip G. , Bangham Charles R. M. , Hawke Simon
Published: March 2007

The capacity of a memory cytotoxic T lymphocyte (CTL) population to protect against viral infections is well established, but the processes underlying this protection are less well understood. We have used heterotypic intranasal immunization with influenza A/X31 (H3N2) to protect against a subsequent infection with the neurovirulent influenza A/WSN (H1N1) in either the cerebrospinal fluid or the immunoprivileged brain parenchyma. Viral clearance from both sites was associated with a local infiltration and proliferation of A/WSN‐specific CD8+ T cells. Infection in the cerebrospinal fluid elicited a proliferative response in the draining lymph nodes, an anti‐H1N1 serum antibody response and an increase in the extracerebral A/WSN‐specific CTL precursor frequency. In contrast, infection in the brain parenchyma elicited no lymph node proliferative response or serum antibody response and caused a transient decrease in the extracerebral CTL precursor frequency. Thus the memory CTL population protected against an intracerebral viral infection independent of any immune response occurring in systemic lymphoid tissue.
Lipopolysaccharide complexed with soluble CD14 binds to normal human monocytes
Authors: Blondin Catherine , Le Dur Annick , Cholley Béatrice , Caroff Martine , Haeffner‐Cavaillon Nicole
Published: March 2007

Using flow cytometry we have compared the binding of Neisseria meningitidis lipopolysaccharide labeled with fluorescein isothiocyanate (FITC‐LPS) to normal human monocytes in whole blood with the binding to Chinese hamster ovary (CHO) cells transfected with human CD14 gene (hCD14‐CHO cells). Binding of FITC‐LPS to cells was dose dependent, saturable and enhanced in the presence of increasing concentrations of serum. Blockade of membrane CD14 with saturating concentrations of anti‐CD14 monoclonal antibody (mAb) My4 inhibited 50% of the binding of FITC‐LPS to monocytes and 100% to hCD14‐CHO cells. Similarly, removal of membrane CD14 by phosphatidylinositol phospholipase C (Pl‐PLC) treatment of the cells partially decreased the binding of FITC‐LPS to monocytes but totally inhibited the binding to hCD14‐CHO‐transfected cells. These results suggest that binding of FITC‐LPS to monocytes is not only mediated by membrane CD14. Using two‐color flow cytometry, we observed that FITC‐LPS binds to My4‐saturated monocytes in association with soluble (s)CD14 present in serum as revealed by staining with rhodaminelabeled My4 mAb. The binding of FITC‐LPS/sCD14 complexes to monocytes treated with saturating amounts of unlabeled My4 prior to addition of the complexes was completely inhibited by anti‐CD14 mAb 10G33. When cells were first saturated with a mixture of My4 and 10G33 mAb, washed and further incubated with FITC‐LPS/sCD14, inhibition of the binding of LPS was similar to that observed with cells saturated with My4 alone, showing that the binding of FITC‐LPS is not mediated by the 10G33 epitope present on mCD14. These results suggest that either the 10G33 epitope on sCD14 is involved in the binding of LPS/sCD14 complexes to the cells, or that 10G33 mAb inhibits the binding of FITC‐LPS to sCD14. Taken together, these data indicate that sCD14 which is present in normal serum, in addition to membrane CD14, enables LPS to bind monocytes through an as yet unidentified molecule and that sCD14 does not simply serve as a shuttle for transfer of LPS to membrane CD14.
CD8+ T cells control Th2‐driven pathology during pulmonary respiratory syncytial virus infection
Authors: Hussell Tracy , Baldwin Christopher J. , O'Garra Anne , Openshaw Peter J. M.
Published: March 2007

BALB/c mice vaccinated with vaccinia virus expressing the major surface glycoprotein G of respiratory syncytial virus (RSV) develop lung eosinophilia during RSV challenge. The G protein is remarkable in that it induces CD4+, but no CD8+ T cells in this mouse strain. Studies using passive T cell transfers show that co‐injection of CD8+ T cells greatly reduces the Th2‐driven lung eosinophilia caused by G‐specific CD4+ T cells. By contrast, vaccination with the fusion protein (F) induces both CD8+ and CD4+ T cells, but not lung eosinophilia during RSV infection. These observations suggest that CD8+ T cells play a crucial role in preventing Th2‐driven pathology. We therefore depleted mice with anti‐CD8 antibodies in vivo. This treatment allowed lung eosinophilia to develop in F‐primed mice. Depletion of interferon (IFN)‐γ had a similar effect, suggesting that secretion of this cytokine is the mechanism by which CD8+ T cells exert their effect. To test whether similar effects occurred in other strains of mice, RSV‐infected C57BL/6 mice (which do not develop eosinophilia after sensitization to G) were treated with anti‐IFN‐γ. Again, these mice developed eosinophilia. In this strain, genetic deletion of CD8‐α, β2‐microglobulin or genes coding for the transporter associated with antigen presentation (which in each case eliminates CD8+ T cells) caused lung eosinophilia during RSV infection. These studies show the critical roles that CD8+ T cells and IFN‐γ production play in regulating Th2‐driven eosinophilia and provide a unifying explanation for previous studies of lung eosinophilia. We propose that vaccines designed to enhance CD8+ T cell recognition might avoid disease caused by CD4+ Th2 cells.
The nature of the signals regulating CD8 T cell proliferative responses to CD8α+ or CD8α− dendritic cells
Authors: Winkel Kenneth D. , Kronin Vadim , Krummel Matthew F. , Shortman Ken
Published: March 2007

The CD8α−‐expressing dendritic cells (DC) of mouse spleen have been shown to be poor inducers of interleukin (IL)‐2 production by CD8 T cells when compared to the CD8− DC. As a consequence, CD8 T cells give a more prolonged proliferative response to CD8− DC than to CD8+ DC. The possible mechanisms underlying these functional differences in DC subtype have been investigated. Inadequate co‐stimulation did not underlie the poor T cell response to allogeneic CD8+ DC. Equivalent levels of B7‐1 (CD80) and B7‐2 (CD86) were found on the two DC subtypes and co‐stimulator assays did not reveal any functional differences between them. Although CD8+ DC were found to die more rapidly in culture than CD8− DC, this did not explain their reduced stimulatory ability. Neither prolonging DC survival in culture nor renewing the stimulator cells by repeated addition of freshly isolated DC had any significant effect on the T cell responses. Furthermore, later addition to the cultures of DC of the opposite type to the initiating DC did not reverse or eliminate the differential response to the initiating DC. The role of DC‐derived soluble factors was examined by addition to the cultures of supernatants derived from freshly isolated or stimulated DC of the opposite type. This neither enhanced the poor stimulatory capacity of CD8+ DC nor inhibited the stimulation by CD8− DC. Furthermore, addition of a series of cytokines that might have been produced by the DC did not eliminate the differences in T cell proliferation. Only the addition to the cultures of the growth factors IL‐2 and IL‐4 overcame the stimulatory difference between the two DC populations, confirming that the difference in T cell proliferative responses was a consequence of differences in induced cytokine production. The difference in the response of CD8 T cells to CD8+ and CD8− DC is therefore determined by direct DC‐T cell contact during the earliest stages of the culture and involves an undetermined and possibly new signaling system.
Polythiacrown Macro‐ and Gigantocycles with Chiral Diacetal Cores
Authors: Abramson Sarah , Berkovich‐Berger Dvora , Dagan Shai , Goldberg Israel , Golender Lara , Grabarnik Mikhail , Lemcoff N. Gabriel , Weinman Sarah , Fuchs Benzion
Published: March 2007

We present a unique class of polythiacrown macro‐ and gigantocyclic[9] systems, consisting of ethylene 1,2‐dithioglycol (ETG) to poly(ethylene thioglycol) (ETGn) bridges over one to six diacetal units of the cis‐1,3,5,7‐tetraoxadecalin (TOD) type. The latter is a dissymmetric, chiral moiety, incorporating a cavity with built‐in high electron lone pair concentration, serving as the “core” of chiral macrocyclic host systems with good inclusion ability of ions and polar molecules. We describe two approaches: (i) the reactions of the 2,6‐bis(bromomethyl)‐cis‐TOD podand (6) with ETG or higher ETGns (12n), in Cs2CO3 promoted processes, leading to the innate but uncontrolled formation of polythiacrown‐TOD macrocycles having ETG/TOD ratios of 1:1 (7), 2:2 (8) and further 3:3–6:6 (111/m)10 macrocycles via open dithiol intermediates, and (ii) judicious preparation, using K2CO3, of oligomeric dibromide intermediates with ETGn:TOD ratios 1:2, 2:3 or 3:4 (14n/m), which led (with further ETGn) in a controlled way to the 2:2 (8n), or 3:3, 4:4 and 6:6 (11n/m) macro‐ and gigantocyclic systems. Altogether, the outcome of these processes depends on the relative concentrations of the reactants. Synthesis was accompanied by detailed (NMR and MS) spectroscopy. X‐ray crystallographic analysis of a number of macrocycles, complemented by (MM & MD) computation, made possible valuable structural, stereochemical and conformational analysis. While sophisticated in their stereochemical features, these systems are readily prepared in enantiopure form and hold great promise of chemical reactivity in metal ion inclusion and molecular and chiral recognition.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)
On the Functionalization of [2.2](1,4)Phenanthrenoparacyclophane
Authors: Hopf Henning , Hucker Joachim , Ernst Ludger
Published: March 2007

Two routes for preparing functionalized [2.2](1,4)phenanthrenoparacyclophanes are described: either the parent system 2 is subjected to electrophilic substitution (bromination, Friedel–Crafts acylation, Rieche formylation: preparation of 5, 6, 7, 11 and 12) or the desired substituents are incorporated in the early stages of the synthesis by the preparation of the corresponding functionalized styryl paracyclophanes and their photocyclization to the respective phenanthrenocyclophanes. By these specific routes various bromides (22a,b), ethers (28a–c) and phenols (29a,b) were synthesized. The latter derivatives, on oxidation, furnish para‐ (31) and ortho‐quinonophanes (30, 32, 33), useful substrates for the preparation of cyclophanes containing phenazine subunits (36). The stilbene → phenanthrene photocyclization can also be employed for the preparation of benzothiophenophanes, e.g. 43 and 44, from the respective precursors. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)
Pro‐eating disorder websites: users' opinions
Authors: Csipke Emese , Horne Outi
Published: March 2007

The phenomenon of ‘pro‐eating disorder’ websites remains relatively unexplored by researchers in published formats. Supporters of the sites claim beneficial effects but health professionals worry that the sites propagate disordered behaviours. The present study addressed visitor characteristics and perceived impact of visits. A 24‐item questionnaire supplemented with the Eating Attitudes Test‐26 (EAT‐26) was developed and posted on the website of the UK mental health charity SANE. Participants who interacted with others on the sites and sought emotional support reported improved mental state after visiting, and for them, evidence was found of reduced impact from potentially damaging content. ‘Silent browsing’ in order to sustain a disorder was found to be mainly harmful. ‘Silent browsers’ may be particularly vulnerable to a worsening of their symptoms in the absence of beneficial effects from emotional support, but those who interact and find support could face a danger of a different sort. © 2007 John Wiley & Sons, Ltd and Eating Disorders Association.
Making choices between prepayment and user charges in Zambia. What are the results for equity?
Authors: Kondo Masahide , McPake Barbara
Published: March 2007

In many low‐income countries, user charges were introduced in the 1990s. As problems emerged of equity of access, interest grew in developing prepayment mechanisms to protect users from risk of out‐of‐pocket payments. In Zambia, a prepayment scheme did not generate sufficient revenue, due to abuses of its terms. An alternative scheme using discount cards (a set of coupons to cover episodes of care at discount) was devised.

We aimed to understand the equity implications of prepayment and discount cards relative to user charges. We proposed models predicting roles of income, perceived health status, perceived quality of care and time preference in choice of payment mechanism and use of health services. We tested these models using three data sets that could be accessed or collected.

It is concluded that relative to user charges, prepayment may facilitate access without incurring income‐related equity losses. Evidence concerning discount cards was weaker. We concluded that they facilitate access to a lesser extent.

Discount cards offer a credible intermediate solution between user charges and prepayment that avoid some problems associated with prepayment. However, since prepayment seems to be associated with the most positive outcomes, finding other solutions to their problems would be preferred. Copyright © 2007 John Wiley & Sons, Ltd.
Health insurance coverage and the use of preventive services by Mexican adults
Authors: Pagán José A. , Puig Andrea , Soldo Beth J.
Published: March 2007

The lack of health insurance coverage could be a potentially important deterrent to the use of preventive health care by older adults with high rates of chronic co‐morbidities. We use survey data from 12 100 Mexican adults ages 50 and older who participated in the 2001 Mexican Health and Aging Study (MHAS) to analyze the relation between health insurance coverage and the use of preventive health‐care services in Mexico. Uninsured adults were less likely to use preventive screenings for hypertension, high cholesterol, diabetes and (breast, cervical and prostate) cancer than insured adults. After adjusting for other factors affecting preventive care utilization in a logistic regression model, we found that these results still hold for high cholesterol and diabetes screening. Similar results hold for the population not working during the survey week and for adults earning below 200% of the poverty line. Our results suggest that insured adults are in a relatively better position to detect some chronic diseases – and have them treated promptly – than uninsured adults because they have better access to cost‐effective preventive screenings. Recent public policy initiatives to increase health insurance coverage rates in Mexico could lead to substantially higher preventive health‐care utilization rates and improvements in population health. Copyright © 2007 John Wiley & Sons, Ltd.
Presynaptic calcium stores contribute to nicotine‐elicited potentiation of evoked synaptic transmission at CA3‐CA1 connections in the neonatal rat hippocampus
Authors: Le Magueresse Corentin , Cherubini Enrico
Published: March 2007

Nicotine acetylcholine (ACh) receptors (nAChRs) are ligand‐gated ion channels that are widely expressed throughout the central nervous system. It is well established that presynaptic, α7‐containing nAChRs modulate glutamate release in several brain areas, and that this modulation requires extracellular calcium. However, the intracellular mechanisms consecutive to nAChR opening are unclear. Recent studies have suggested a role for presynaptic calcium stores in the increase of neurotransmitter release following nAChR activation. Using the minimal stimulation protocol at low‐probability Schaffer collateral synapses in acute hippocampal slices from neonatal rats, we show that nicotine acting on presynaptic α7 nAChRs persistently upregulates glutamate release. We tested the role of calcium stores in this potentiation. First, we examined the relationship between calcium stores and glutamate release. We found that bath application of SERCA pump inhibitors (cyclopiazonic acid and thapsigargin), as well as an agonist of ryanodine receptors (ryanodine 2 μM) increases the probability of glutamate release at CA3‐CA1 synapses, decreases the coefficient of variation and the paired‐pulse ratio, indicating that presynaptic activation of calcium‐induced calcium release can modulate glutamatergic transmission. Next, we investigated whether blocking calcium release from internal stores could alter the effect of nicotine. Preincubation with thapsigargin (10 μM), cyclopiazonic acid (30 μM), or with a high (blocking) concentration of ryanodine (100 μM) for 30 min to 5 h failed to block the effect of nicotine. However, after preincubation in ryanodine, nicotine‐elicited potentiation was significantly shortened. These results indicate that at immature Schaffer collateral‐CA1 synapses, activation of presynaptic calcium stores is not necessary for but contributes to nicotine‐elicited increase of neurotransmitter release. © 2007 Wiley‐Liss, Inc.
Steroid pregnenolone sulfate enhances NMDA‐receptor‐independent long‐term potentiation at hippocampal CA1 synapses: Role for L‐type calcium channels and sigma‐receptors
Authors: Sabeti Jilla , Nelson Thomas E. , Purdy Robert H. , Gruol Donna L.
Published: March 2007

Severe stress elevates plasma and CNS levels of endogenous neuroactive steroids that can contribute to the influence of stress on memory formation. Among the neuroactive steroids, pregnenolone sulfate (PREGS) reportedly strengthens memories and is readily available as a memory‐enhancing supplement. PREGS actions on memory may reflect its ability to produce changes in memory‐related neuronal circuits, such as long‐term potentiation (LTP) of excitatory transmission in hippocampus. Here, we report a previously undiscovered pathway by which PREGS exposure promotes activity‐dependent LTP of field excitatory postsynaptic potentials at CA1 synapses in hippocampal slices. Thus, application of PREGS, but not the phosphated conjugate of the steroid, selectively facilitates the induction of a slow‐developing LTP in response to high‐frequency (100 Hz) afferent stimulation, which is not induced in the absence of the steroid. The slow‐developing LTP is independent of NMDA‐receptor function (i.e., dAP5 insensitive) but dependent on functional L‐type voltage‐gated calcium channels (VGCC) and sigma‐receptors. By contrast, PREGS at the highest concentration tested produces a depression in NMDA‐receptor‐dependent LTP, which is evident when sigma‐receptor function is compromised by the presence of a sigma‐receptor antagonist. We found that at early times during the induction phase of L‐type VGCC‐dependent LTP, PREGS via sigma‐receptors transiently enhances presynaptic function. As well, during the maintenance phase of L‐type VGCC‐dependent LTP, PREGS promotes a further increase in presynaptic function downstream of LTP induction, as evidenced by a decrease in paired‐pulse facilitation. The identification of complex regulatory actions of PREGS on LTP, involving sigma‐receptors, L‐type VGCCs, NMDA‐receptors, and inhibitory circuits will aid future research endeavors aimed at understanding the precise mechanisms by which this stress‐associated steroid may engage multiple LTP‐signaling pathways that alter synaptic transmission at memory‐related synapses. © 2007 Wiley‐Liss, Inc.
Infection as a cause of early relapse in patients recovering from thrombotic thrombocytopenic purpura
Authors: Illoh Orieji C.
Published: March 2007

Thrombotic thrombocytopenic purpura (TTP) is a rare but severe disorder characterized by hemolytic anemia, thrombocytopenia, fever, renal failure, and neurologic manifestations. Plasma exchange is the most effective treatment for this condition reducing mortality from 90% in untreated patients to 10%. However, infections acquired during the course of therapy could lead to early relapse of TTP. In this case report, we report three patients with TTP who initially responded well to plasma exchange treatments but suffered early relapses following bacterial infections. All these patients achieved remission once appropriate antibiotic therapy was instituted although one patient eventually received four courses of rituximab. This report emphasizes the need to be vigilant for new infections especially urinary tract infections in TTP patients undergoing plasma exchange. Instituting appropriate antibiotic therapy once an infection is suspected may reduce the need for prolonged plasma exchange procedures and extended hospital stay. J. Clin. Apheresis. © 2007 Wiley‐Liss, Inc.
Interfacing Q‐Chem and CHARMM to perform QM/MM reaction path calculations
Authors: Woodcock H. Lee , Hodošček Milan , Gilbert Andrew T. B. , Gill Peter M. W. , Schaefer Henry F. , Brooks Bernard R.
Published: March 2007

A hybrid quantum mechanical/molecular mechanical (QM/MM) potential energy function with Hartree‐Fock, density functional theory (DFT), and post‐HF (RIMP2, MP2, CCSD) capability has been implemented in the CHARMM and Q‐Chem software packages. In addition, we have modified CHARMM and Q‐Chem to take advantage of the newly introduced replica path and the nudged elastic band methods, which are powerful techniques for studying reaction pathways in a highly parallel (i.e., parallel/parallel) fashion, with each pathway point being distributed to a different node of a large cluster. To test our implementation, a series of systems were studied and comparisons were made to both full QM calculations and previous QM/MM studies and experiments. For instance, the differences between HF, DFT, MP2, and CCSD QM/MM calculations of H2O···H2O, H2O···Na+, and H2O···Cl− complexes have been explored. Furthermore, the recently implemented polarizable Drude water model was used to make comparisons to the popular TIP3P and TIP4P water models for doing QM/MM calculations. We have also computed the energetic profile of the chorismate mutase catalyzed Claisen rearrangement at various QM/MM levels of theory and have compared the results with previous studies. Our best estimate for the activation energy is 8.20 kcal/mol and for the reaction energy is −23.1 kcal/mol, both calculated at the MP2/6‐31+G(d)//MP2/6‐31+G(d)/C22 level of theory. © 2007 Wiley Periodicals, Inc. J Comput Chem, 2007
Coarse‐graining of protein structures for the normal mode studies
Authors: Eom Kilho , Baek Seung‐Chul , Ahn Jung‐Hee , Na Sungsoo
Published: March 2007

The coarse‐grained structural model such as Gaussian network has played a vital role in the normal mode studies for understanding protein dynamics related to biological functions. However, for the large proteins, the Gaussian network model is computationally unfavorable for diagonalization of Hessian (stiffness) matrix for the normal mode studies. In this article, we provide the coarse‐graining method, referred to as “dynamic model condensation,” which enables the further coarse‐graining of protein structures consisting of small number of residues. It is shown that the coarser‐grained structures reconstructed by dynamic model condensation exhibit the dynamic characteristics, such as low‐frequency normal modes, qualitatively comparable to original structures. This sheds light on that dynamic model condensation and may enable one to study the large protein dynamics for gaining insight into biological functions of proteins. © 2007 Wiley Periodicals, Inc. J Comput Chem, 2007
Cytomegalovirus as a frequent cause of Guillain‐Barré syndrome
Authors: Schmitz H. , Enders G.
Published: March 2007

In 10 patients with Guillain‐Barré syndrome a preceeding cytomegalovirus infection could be demonstrated by virus‐specific IgM antibodies that were present in high titers in 9 of the 10 patients in the first serum specimen. The IgM antibodies to cytomegalovirus were detected by a sensitive “double” indirect immunofluorescence technique. In most of our cases (8 of 10) the complement‐fixing antibody titers had already reached high levels on admission into a hospital, and significant titer changes were not observed. Cytomegalovirus was isolated from the urine of five patients.
A study of the prevalence of rotavirus infection in children with gastroenteritis admitted to an infectious diseases hospital
Authors: Birch C. J. , Lewis F. A. , Kennett M. L. , Homola M. , Pritchard H. , Gust I. D.
Published: March 2007

In a 12 month survey of infants and children with gastroenteritis admitted to Fairfield Hospital, Melbourne, rotavirus was found in approximately 42% of patients. This virus was detected more often during the winter months, particularly in children aged between 12 months and 3 years. Detection of rotavirus by electron microscopy was found to be more sensitive than by counterimmunoelectrophoresis. Routine bacterial and viral studies revealed that bacterial pathogens and common enteric viruses were associated with relatively few cases of gastroenteritis. There is little doubt that rotavirus is the most important aetiological agent of acute gastroenteritis in young children in Melbourne.
Solid‐phase microtiter radioimmunoassay for detection of the Norwalk strain of acute nonbacterial, epidemic gastroenteritis virus and its antibodies
Authors: Greenberg Harry B. , Wyatt Richard G. , Valdesuso Jose , Kalica Anthony R. , London William T. , Chanock Robert M. , Kapikian Albert Z.
Published: March 2007

The development of microtiter solid‐phase radioimmunoassays for the detection of Norwalk antigen and its antibody is described. The tests are simple to perform and are sensitive and specific. The test for antigen can be used on crude stool filtrates and suspensions. Both tests are at least as sensitive as immune electron microscopy and more sensitive than immune adherence assay.
Thermal treatment and infectivity of hepatitis A virus in human feces
Authors: Peterson D. A. , Wolfe L. G. , Larkin E. P. , Deinhardt F. W.
Published: March 2007

The susceptibility of white‐lipped marmoset monkeys (Saguinus sp) to human hepatitis A virus (HAV) provides a system for evaluation of thermal inactivation of HAV in feces and contaminated shellfish. Intramuscular or oral administration of HAV derived from feces of four patients with acute hepatitis A induced hepatitis in 28–100% of the inoculated marmosets. A 10% (w/v) fecal pool (GBG‐BM) prepared from two patients (GBG and GBM) induced hepatitis in marmosets (2/4 with 1 ml; 2/2 with 3 ml) when given orally as a 1:3 dilution. A HAV‐baby food raw oyster mixture fed to fasted marmosets induced hepatitis in 1/4 and seroconversion in 2/4 animals. Two groups of oysters were injected with HAV (concentrated 3:1 by centrifugation of the GBG‐BM pool); one group was treated at 140°F for 19 minutes and the other served as an untreated control. In animals fed the untreated inoculum, 4/6 developed hepatitis and 6/6 seroconverted, whereas of those fed the heattreated inoculum 1/7 developed hepatitis and 2/7 seroconverted. These data suggest that pasteurization methods could be developed that would eliminate shellfish‐associated hepatitis A and retain the palatability of the shellfish.
Hepatitis B virus DNA in primary hepatocellular carcinoma tissue
Authors: Summers Jesse , O'Connell Anna , Maupas Philippe , Goudeau Alain , Coursaget Pierre , Drucker Jacques
Published: March 2007

Tumour, cirrhotic, and metastatic tissues from four patients with primary hepatocellular carcinoma have been investigated for the presence of hepatitis B viral DNA by nucleic acid hybridization.

Tumours from two of three patients with a current HBV infection contained 1–2 genomes per cell of unintegrated viral DNA, while tumours from the third HBs antigen‐positive patient contained less than one genome equivalent per ten cells. A tumour from one patient with anti‐HBs contained no detectable HBV DNA.

A variety of models involving HBV as an etiologic agent may be advanced to explain the statistical correlation of HBV infection with primary hepatocellular carcinoma (PHC). The data presented here argue against the model that HBV DNA integrated into every cell is required to maintain the oncogenic transformation of hepatocytes, but they do not rule out other models.
Determination of coronavirus 229E antibody by an immune‐adherence hemagglutination method
Authors: Gerna Giuseppe , Achilli Giorgio , Cattaneo Ercole , Cereda Paolo
Published: March 2007

An immune‐adherence hemagglutination (IAHA) method for coronavirus 229E antibody determination has been developed both for diagnosis of recent infections and for detection of long‐past infections. Results have been compared with those obtained by complement fixation (CF), neutralization (Nt), and indirect hemagglutination (IHA) tests. The IAHA method has been shown to be as sensitive as the CF, Nt, and IHA tests in detecting cases of acute 229E infection. However, in a seroepidemiological survey of 343 healthy people of all ages, IAHA detected 229E antibody in 254 individuals (74.0%), Nt in 166 (48.3%), IHA in 89 (25.9%), and CF in 30 (8.7%). A study of the prevalence of coronavirus 229E IAHA antibody in the different age groups has shown that during the second decade of life nearly 100% of the population acquire this type of antibody, whereas only 50% are positive at the end of the first decade. In the older age groups, the high frequency of CF antibody (“marker” of recent infection) indirectly confirms the high rate of 229E reinfections and the nonprotective nature of IAHA antibody. CF titer ⩾ 1:8 in 90% of cases corresponded to IAHA titers ⩾ 1:64. However, sera with IAHA titers of ⩾ 1:128 were often CF‐negative. Recent 229E infections (or reinfections), as determined by the presence of CF antibody, were more frequent in April‐May than in October‐November. Three cases of acute infection showing 229E seroconversion (two adults and one child) were observed during the winter‐spring season. IAHA appears to be the test of choice for seroepidemiological surveys.
Epidemiology of cytomegalovirus infection in end stage renal disease
Authors: Betts Robert F. , Cestero Rafael V. M. , Freeman Richard B. , Douglas R. Gordon
Published: March 2007

Since primary cytomegalovirus (CMV) infection is a cause of morbidity among renal transplant recipients, we undertook a prospective study of our maintenance hemodialysis patients and personnel to determine whether these sources posed a risk for transmission of CMV. Our study of 85 patients and 49 personnel showed that CMV was detected in eight nontransplanted, older dialysis patients and 13 patients who had lost their allograft. In spite of the presence of CMV on the unit, no patient or staff member developed primary infection from interpersonal transmission or from transfused frozen red blood cells. All primary infections in renal transplant patients could be accounted for by acquisition from the transplanted kidney, thus eliminating the dialysis unit or frozen blood as a risk to either patients or personnel.
Comparative studies of five strains of mumps virus in vitro and in neonatal hamsters: evaluation of growth, cytopathogenicity, and neurovirulence
Authors: McCarthy Micheline , Jubelt Burk , Fay Dianne B. , Johnson Richard T.
Published: March 2007

The growth and Cytopathogenicity of five strains of mumps virus were examined in six types of cell cultures and in neonatal hamsters. These strains included the MJ and RW strains, both recent cerebrospinal fluid isolates; the neuroadapted Kilham strain; the Enders strain adapted to chick embryo; and the Jeryl Lynn vaccine strain adapted to chick cell culture. The MJ, RW, and Kilham strains all produced infectious virus without restriction in vitro, but the RW strain did not cause obvious cytopathic effect; the MJ and Kilham strains were cytopathic. The Enders and Jeryl Lynn strains adapted to chick embryo cells were cytopathic and productive in chick cell culture but were restricted in ability to grow productively in vitro on mammalian cell types, even failing to produce noninfectious particles in some cases. In vitro Cytopathogenicity was a host‐independent property of a specific virus strain, but the type of cytopathic effect manifest in culture (eg, fusion, cytoplasmic vacuoles) depended on both the strain and the host cell. The ability of a virus strain to invade the brain parenchyma and infect neurons in vivo appeared to correlate with the strain's Cytopathogenicity and not with passage history or adaptive status.
Infectivity liters of enterovirus as found in human stools
Authors: Melnick J. L. , Rennick V.
Published: March 2007

Data have been gathered and collated from a variety of sources both published and unpublished, dealing with the concentration of enteroviruses in human stools. For polioviruses, a general range of 3.0–6.5 log10TCD50* per gram of stool was reported, whereas for coxsackieviruses and echoviruses the range has been from 2.0–5.5 log10TCD50. As human stools average about 100 gm, it is not unusual for an infected person to excrete as much as 10–300 million TCD50of virus daily.

The results of enterovirus titrations are significantly affected by the types of cultures in which the tests are conducted. With certain kinds of cultures (eg, human kidney for polioviruses), comparative tests showed titers to be at least one log unit higher per gram of stool than the titers of the same strains titrated in monkey kidney cultures. Since almost all of the titrations included in this report were carried out in monkey kidney cultures, the concentration of virus in many cases may be assumed to be ten times higher than that reported.

Some of the data collected also contributed information on the duration of enterovirus excretion. These data reemphasize the fact that a person in the course of an asymptomatic enterovirus infection may excrete the virus over a period of many weeks, with about 50% of those infected continuing to shed virus into the third and fourth weeks of infection.
Hepatitis b surface antigen production as a growth cycle‐related terminal event in plc/prf/5 hepatoma cells
Authors: Copeland Jennifer A. , Skelly Jacinta , Mann George F. , Howard Colin R. , Zuckerman Arie J.
Published: March 2007

The dynamics of hepatitis B surface antigen production by PLC/PRF/5 hepatoma cells were studied using a quantitative radioimmunoassay method. Maximum rates of antigen production were found in nutrient‐depleted, non‐dividing cultures and were temporally related to cytological changes preceding cell death. These results indicate that antigen production may be cell‐cycle related and represent a terminal event.
Human infection by a bovine strain of parainfluenza virus type 3
Authors: Ben‐Ishai Z. , Naftali V. , Avram A. , Yatziv S.
Published: March 2007

Etiological relationship between a bovine strain of parainfluenza virus type 3 and pneumonia in a child is suggested. Haemagglutination inhibition tests have clearly demonstrated that specific antibodies against the bovine virus were present in the patient's serum. The significance of this finding in relation to human infection is discussed.
Inhibition of influenza a virus replication by rifampicin and selenocystamine
Authors: And Mansoor Hamzehei , Ledinko Nada
Published: March 2007

The effects of selenocystamine, an inhibitor of influenza virus RNA‐dependent RNA polymerase in vitro activity, and the antibiotic rifampicin were studied on influenza A/PR/8/34 (HON1) infection in embryonated eggs. Both drugs completely inhibited hemagglutinating and infective virus yields when added at relatively early times postinfection. Maximal inhibition was produced by apparently noncytotoxic concentrations of 50 m̈g of selenocystamine, or of 400 m̈g of rifampicin, per egg.
Antibody reactive in antibody‐dependent cell‐mediated cytotoxicity following influenza virus vaccination
Authors: Vella Stefano , Rocchi Giovanni , Resta Silvia , Marcelli Marcello , Felici Annapaola De
Published: March 2007

The antibody reactive in antibody‐dependent, cell‐mediated cytotoxicity (ADCC) to influenza virus‐infected cells was measured in two groups of seven volunteers each, before and after immunization with inactivated or live attenuated A/Victoria/3/75 influenza virus vaccines. Age‐matched controls were seven adult individuals who experienced natural influenza infection due to A/Victoria/3/75‐like virus strain.

After inactivated whole influenza virus immunization all the subjects showed a significant rise of the antibody reactive in ADCC (from a mean value of 4.7% to 17.1% cytotoxicity, before and 5 weeks after immunization, respectively) as well as of hemagglutination inhibition (HI) antibody (fourfold or greater increase). These immune responses were similar to those observed among naturally infected controls. After live attenuated virus vaccination, no significant increase in titer of antibody reactive in ADCC was detected, even though the vaccine induced significant increase of HI antibody titer.

Little correlation was found between ADCC and HI antibody rises in sera of recipients of inactivated virus vaccine and of naturally infected individuals, while, in live attenuated influenza virus vaccinees, the rise of HI antibody titer did not correspond to a significant increase of ADCC antibody titer; several subjects who developed a significant rise in ADCC antibody titer did not show significant variation in antibody to neuraminidase and/or to complement fixation influenza virus antigens.
Characterization of candidate adenovirus 37 by SDS‐polyacrylamide gel electrophoresis of virion pplypeptides and DNA restriction site mapping
Authors: Wadell Göran , Sundell Gunnar , De Jong Jan C.
Published: March 2007

A new human adenovirus has been isolated from patients with keratoconjunctivitis and/or genital infection since 1976. This adenovirus, designated candidate adenovirus 37 (Ad 37) is serologically distinct but related to Ad 10, 13, 19, and 30 (see the accompanying paper by de Jong et al). SDS‐Polyacrylamide gel electrophoresis of Ad 37 virion polypeptides showed that this adenovirus is a member of subgroup D. DNA restriction endonuclease analysis of DNA from Ad 37 and related serotypes belonging to subgroup D showed that Ad 37 is a new genome type belonging to subgroup D but clearly distinct from the 20 serotypes classified into this subgroup.
Immunogenicity of influenza A/USSR (H1N1) subunit vaccine in unprimed young adults
Authors: Frank Arthur L. , Paul Glezen W. , Cate Thomas R. , Webster Robert G.
Published: March 2007

Purified subunit vaccines (HANAflu) containing 20 /xg of hemagglutinin of influenza A/USSR/90/77 (H1N1) alone or with 1–5% whole virus were compared to commercially available vaccines for reactogenicity and immunogenicity in unprimed young adults. Reactions to all vaccines were minimal. Sera from volunteers who received two intramuscular doses of vaccine or placebo were tested by hemagglutination‐inhibition and neutralization tests. HANAflu with 1 m̈g (5%) whole virus added was not different in immunogenicity from commercial vaccine. Both commercial vaccine and HANAflu with 1 m̈g whole virus added gave higher seroconversion rates and more neutralization titers ≥ 4 log2 than HANAflu alone and HANAflu + 0.2 m̈g (1%) whole virus. Thus, the HANAflu subunit vaccine alone was less immunogenic than commercial vaccine in unprimed persons. However, addition of 1 m̈g (5%) whole virus, but not 0.2 m̈g (1%), eliminated this difference. There may be a role for addition of small amounts of whole virus to subunit influenza vaccines to overcome lower immunogenicity in unprimed populations.
The risk of nosocomial hepatitis A and B virus infections from patients under care without isolation precaution
Authors: Papaevangelou George J. , Roumeliotou‐Karayannis Anastasia J. , Contoyannis Panayotis C.
Published: March 2007

The risk of nosocomial viral hepatitis cross‐infection was investigated in a prospective study of 248 adult patients hospitalized in the Infectious Diseases Hospital of Athens for acute viral hepatitis. They were followed‐up clinically, biochemically, and serologically for 100 to 250 days after admission to the Hospital. Commercially available radioimmunoassays were used for the detection of the surface antigen of HBV (HBsAg), its antibody (Anti‐HBs), the antibody to the core of the HBV (Anti‐HBc), and the IgG and IgM antibodies to the HAV. Clinical, biochemical, or serological indications of hospital cross‐infection were not detected in any of the 21 susceptibles to HAV infection or among the 46 susceptibles to HBV infection during the follow‐up period, although all of them had ample opportunity for cross‐infection through close contact to acutely ill patients. These data provide further evidence that HBV and HAV are not easily transmitted from patients hospitalized for acute viral hepatitis to other susceptible patients sharing wards, and indicate that there is need for reconsideration of the present strategy of hospitalization and care of acutely ill viral hepatitis patients.
Detection of measles antigen in conjunctival epithelial lesions staining by lissamine green during measles virus infection
Authors: Nommensen F. E. , Dekkers N. W. H. M.
Published: March 2007

In a study in Kenya of corneal lesions occurring in children with measles virus infection, conjunctival lesions of a characteristic appearance were seen concomitant with the rash. The lesions became visible after staining by Lissamine green or Rose Bengal.

In order to investigate whether these lesions were virus‐induced, paired biopsies were performed on the conjunctiva of five measles patients. One biopsy was taken of a staining lesion; the other one, taken of nonstaining conjunctiva of the same eye, served as control.

Measles‐specific immunofluorescence on cryostate sections of the biopsies showed that in all patients the antigen occurred in the conjunctival epithelial cell layer in the staining lesions only.

The coincidence of epithelial staining and presence of measles antigen suggests a viral origin of the conjunctival lesion. Fluorescent antibody technique on cryostate sections proved to be a suitable method to demonstrate the presence of virus where isolation fails and serology is not applicable.
The spread and persistence of influenza viruses in normal and cyclophosphamide‐treated mice
Authors: Abou‐Donia H. , Jennings R. , Potter C. W.
Published: March 2007

The persistence and extrapulmonary spread of three strains of influenza virus, the mouse neuro‐adapted A/NWS virus, the wild‐type strain A/Victoria/75, and a recombinant virus RIT4050, bearing surface antigens derived from A/ Victoria/75, were studied in both normal and cyclophosphamide‐treated CBA mice following either intranasal or intracerebral inoculation. All three viruses showed increased lethality in mice in the presence of cyclophosphamide but exhibited distinctive patterns of replication and spread. The recombinant virus RIT4050 showed a reduced ability to replicate, persist, and spread in CBA mice compared to either A/NWS or A/Victoria/7 5 viruses, and in general, the A/NWS virus persisted to a greater extent than the A/Victoria/75 virus in both normal and treated mice. However, in the presence of cyclophosphamide, no extrapulmonary spread of A/NWS virus was observed. The reasons for the differences are discussed.
Further evidence for common antigens in herpes simplex and varicella‐zoster viruses
Authors: Schmidt Nathalie J.
Published: March 2007

To elucidate the mechanism of heterologous antibody responses to herpes simplex virus (HSV) and varicella‐zostcr virus (VZV) which occur in some patients with HSV or VZV infections, stronger evidence was sought for the existence of cross‐reacting antibodies to these viruses, using antibody absorption procedures. Absorption of sera from initial HSV infections with HSV antigen was found to abolish heterologous antibody titer rises to VZV, as demonstrated in complement fixation, neutralization, and anti‐complement immunofluorescence test systems. In most instances, convalescent‐phase titers to heterologous VZV were reduced by HSV absorption to levels comparable to those in the acute‐phase serum, indicating that cross‐reacting antibodies were, in fact, responsible for the heterologous antibody titer rises. Absorption of convalescent‐phase sera from HSV or VZV patients with homologous antigen also abolished or greatly diminished immunoprecipitating activity with the heterologous antigen, furnishing additional evidence of the existence of cross‐reacting antibodies. Absorption of sera with insolubilized IgG to reremove rheumatoid factor, which was present in a number of the sera studied, had no effect on either homologous or heterologous antibody titer increases. The demonstration of cross‐reacting antibodies to HSV and VZV supports the concept that these two human herpesviruses share common antigen(s).