bluuebunny/crossref_metadata_2025 huggingface dataset:
Color duplex sonography of occlusion of the common carotid artery with reversed flow in the extracranial internal carotid artery
Authors: Dermitzakis Ioannis , Minardos Ioannis , Kampanarou Matina , Mitakou Diamanto
Published: October 2002

In a small percentage of cases with an occluded common carotid artery (CCA), the patency of the arteries beyond the carotid bulb is preserved. Color duplex sonography is useful for assessing blood flow in these vessels. We present a case of retrograde flow in an internal carotid artery (ICA) with an occluded ipsilateral CCA identified using color duplex sonography in a 70‐year‐old man with diabetes and known atherosclerotic disease. Color duplex sonography revealed that the right CCA was totally occluded near its origin and that flow was re‐established at the bulb. Flow in the right ICA was directed cephalad, with a low‐frequency, damped waveform; flow in the right external carotid artery (ECA) was bidirectional, with increased reversed diastolic flow. Extensive atherosclerotic lesions were also found in the left side. Endarterectomy of the left carotid bifurcation was performed. Follow‐up color duplex sonography 3 months later revealed a small increase of stenosis in the left CCA and mild stenosis in the left ICA. The right CCA remained occluded, but reversed flow with a high‐resistance flow pattern was seen in the ipsilateral ICA that supplied the ECA, which had cephalad‐directed flow. © 2002 Wiley Periodicals, Inc. J Clin Ultrasound 30:388–391, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/jcu.10075
Histological and electrophysiological analysis of the peripheral nerve allografts using an immunosuppressive agent
Authors: Okajima Seiichiro , Hojo Tatsuya , Tamai Kazuo , Takai Shinro , Hirasawa Yasusuke
Published: October 2002

In peripheral nerve allografts, use of an immunosuppressive agent is one of the ways of reducing nerve rejection. FK506 is a newly discovered substance, extracted from Streptomyces tsukubaensis, and has strong immunosuppressive effects. In the present study, immunosuppressive effects of FK 506 were examined using allografts of rat sciatic nerves. Good nerve regeneration was demonstrated through 12 weeks in this model. The immunosuppressed group gained weight over the course of the experiment. Another study was performed to observe the histological changes caused by ceasing the administration of FK506. Administration of FK506 was terminated 12 weeks after grafting. At 8 weeks after cessation, cellular infiltration and large unmyelinated axons were observed in the extended subperineurial space of grafts. At 12 weeks, histological characteristics of rejection were not observed. In the electrophysiological study, the temporal dispersions were recorded at 4 and 8 weeks. However, the normal electrophysiological waves were recorded at 12 weeks after cessation. It was concluded that FK506 is effective for preventing rejection of nerve allografts without any serious side effects on rats, and findings of total rejection of grafts were not recognized after ceasing the administration of FK 506. In peripheral nerve allografts, short‐term administration of an immunosuppressive agent is sufficient to lead to good nerve regeneration. Microsc. Res. Tech. 58:52–58, 2002. © 2002 Wiley‐Liss, Inc.
Introduction to olfactory neuroepithelium
Authors: Nibu Ken‐Ichi
Published: October 2002

Among the five senses, the sense of smell (olfaction) is the most sensitive and emotional window on the outside world (Stern and Marx, 1999). The olfactory system recognizes and discriminates myriad odorants of diverse molecular structures. What makes the olfactory system so specific and sensitive? OE harboring the olfactory receptor neurons (ORNs) also has an another unusual characteristic ability that fascinates scientists. Neurogenesis in this tissue continues throughout lifetime. This unique character provides an elegant model to study neurogenesis and neuronal plasticity, since neuronal birth, differentiation, survival, axon pathfinding, target recognition, synapse formation, and cell death can be examined in the mature OE. This special issue of Microscopic Research and Technique presents the recent developments in this exciting field of neuroscience, “structure and function of olfactory neuroepithelium.” Microsc. Res. Tech. 58:133–134, 2002. © 2002 Wiley‐Liss, Inc.
The electroolfactogram: A review of its history and uses
Authors: Scott John W. , Scott‐Johnson Pamela E.
Published: October 2002

The electroolfactogram (EOG) is a negative electrical potential recorded at the surface of the olfactory epithelium of vertebrates. It represents primarily, if not exclusively, the summated generator potential in the olfactory receptor neurons (ORNs). While a number of studies suggest that secretory or inhibitory events may also contribute to the EOG, these are not well established. This review outlines (1) the cellular and physiological nature of the EOG response; (2) methodological considerations regarding odor selection and delivery, surgical preparation, response descriptions, and analysis; and (3) application of the EOG in human, fish, and insect olfaction and pheromonal responsivity. A number of technical issues associated with EOG recording are also discussed. Microsc. Res. Tech. 58:152–160, 2002. © 2002 Wiley‐Liss, Inc.
Progenitor cells of the olfactory receptor neuron lineage
Authors: Calof Anne L. , Bonnin Alexandre , Crocker Candice , Kawauchi Shimako , Murray Richard C. , Shou Jianyong , Wu Hsiao‐Huei
Published: October 2002

The olfactory epithelium of the mouse has many properties that make it an ideal system for studying the molecular regulation of neurogenesis. We have used a combination of in vitro and in vivo approaches to identify three distinct stages of neuronal progenitors in the olfactory receptor neuron lineage. The neuronal stem cell, which is ultimately responsible for continual neuron renewal in this system, gives rise to a transit amplifying progenitor identified by its expression of a transcription factor, MASH1. The MASH1‐expressing progenitor gives rise to a second transit amplifying progenitor, the Immediate Neuronal Precursor, which is distinct from the stem cell and MASH1‐expressing progenitor, and gives rise quantitatively to olfactory receptor neurons. Regulation of progenitor cell proliferation and differentiation occurs at each of these three cell stages, and growth factors of the fibroblast growth factor (FGF) and bone morphogenetic protein (BMP) families appear to play particularly important roles in these processes. Analyses of the actions of FGFs and BMPs reveal that negative signaling plays at least as important a role as positive signaling in the regulation of olfactory neurogenesis. Microsc. Res. Tech. 58:176–188, 2002. © 2002 Wiley‐Liss, Inc.
Cuticle Ultrastructure Changes in the Crab Scylla serrata Over the Molt Cycle
Authors: Pratoomchat Boonyarath , Sawangwong Pichan , Guedes Ricardo , Reis Maria de lurdes , Machado Jorge
Published: October 2002

Morphological and chemical studies on the cuticle during the molt cycle of the crab Scylla serrata were performed in order to understand the layer formation. Cuticle ultrastructure was studied by scanning electron microscopy (SEM). Energy‐dispersive, X‐ray diffraction, and X‐ray fluorescence analysis were used for identification of the elements and phases in the inner surface of the cuticle. In the first stage (A) of cuticle formation, a thin pellicle organized as an irregular fragmented structure is built. It is composed mainly of α‐chitin/protein β‐keratin‐like complexes where heterogeneous mineral nucleation occur. It is impregnated by ferric concretions, responsible for the brown colour of the carapace. At the beginning of the mineralization process, a spheroidal inorganic phase appears consisting of dicalcium phosphate dihydrate (DCPD) Ca/P=1.00, octacalcium phosphate (OCP) Ca/P=1.33 associated with hydromagnesite and bromapatite traces. During further cuticle development in the remaining A stage and in the beginning of the B stage, calcite and magnesian calcite are formed from the precursor calcium phosphate phase. The next development in the C stages is characterized by intense calcareous thickening consisting mainly of calcite and of magnesian calcite, which become the major mineral fraction of the cuticle. Organic‐inorganic complex precipitations exhibit different aspects as spongiform, filamentary helicoidal, and concentric radial arrangements during C1, C2, and C3, respectively. During different stages of the cuticle formation in Scylla serrata, these mineral deposits may partially result from the balance among different organic contents, mainly between α‐chitin and protein β‐keratin‐like compounds. On the other hand, the calcium crystallization on apatite and calcite polymorphic structures may be influenced by variations of physico‐chemical factors in the cuticle compartment. J. Exp. Zool. 293:414–426, 2002. © 2002 Wiley‐Liss, Inc.
On Cheeger‐type inequalities for weighted graphs
Authors: Friedland Shmuel , Nabben Reinhard
Published: October 2002

We give several bounds on the second smallest eigenvalue of the weighted Laplacian matrix of a finite graph and on the second largest eigenvalue of its weighted adjacency matrix. We establish relations between the given Cheeger‐type bounds here and the known bounds in the literature. We show that one of our bounds is the best Cheeger‐type bound available. © 2002 Wiley Periodicals, Inc. J Graph Theory 41: 1–17, 2002
Social funds as instruments for reducing childhood poverty: lessons from Save the Children's experience
Authors: Marcus Rachel
Published: October 2002

Drawing on Save the Children's experience of working with three social fund financed programmes, this paper examines their potential for reducing childhood poverty. Examining direct and indirect effects on children it discusses the relevance and impact of activities supported, the extent to which the these three social fund programmes reached very poor families and children, and the extent of and mechanisms for poor people's participation. The paper situates this analysis within a discussion of the considers some of the broader factors influencing social fund effectiveness. Copyright © 2002 John Wiley & Sons, Ltd.
Synthesis of 13C‐ and 14C‐labelled catechol
Authors: Ji Rong , Schäffer Andreas
Published: October 2002

13C‐ and 14C‐uniformly labelled catechol was synthesized from phenol in three steps. Phenol was derivatized with 2‐chloro‐5‐nitrobenzophenone in THF containing NaH, followed by ortho‐hydroxylation with 35% aqueous H2O2 in sulphuric acid/glacial acetic acid solution, and by cleavage with piperidine, giving an overall 80% yield with respect to phenol. Copyright © 2002 John Wiley & Sons, Ltd.
Synthesis of stable isotopically labelled versions of lamotrigine and its methylated metabolite
Authors: Manning Calvin O , Wadsworth Alan H , Fellows Ian
Published: October 2002

Lamotrigine is a sodium channel antagonist used for the treatment of epilepsy. Synthesis of stable isotopically labelled (SIL) [M+7] versions of Lamotrigine (1) and its N‐methylated metabolite (2) are described. The routes to prepare these compounds used [M+5] labelled [13C, 15N4]‐aminoguanidine (obtained from labelled thiourea). The overall yield for the metabolite (2) was 34% from [M+3] labelled [13C, 15N2]‐thiourea. Copyright © 2002 John Wiley & Sons, Ltd.
Synthesis and mass spectra of labelled 4(5)‐nitro‐1H‐imidazole‐5(4)‐carbonitriles
Authors: Suwiński J. , Świerczek K.
Published: October 2002

Cine nucleophilic substitution of 1,4‐dinitroimidazole and its 2‐methyl derivative with nitrogen‐15 or carbon‐13 potassium cyanides afforded, respectively, labelled 4(5)‐nitro‐1H‐imidazole‐5(4)‐carbonitriles. Detailed mass spectra analysis led to the conclusion that during fragmentation in mass spectrometer the labelled atoms are present in all the main fragmentation ions of m/z higher than 42. Copyright © 2002 John Wiley & Sons, Ltd.
New characters in the Gnathostomulid mouth parts revealed by scanning electron microscopy
Authors: Sørensen Martin Vinther , Sterrer Wolfgang
Published: October 2002

An analysis with SEM of the mouth parts of 16 species belonging to 10 genera of Gnathostomulida resulted in the following new characters and conclusions: 1) At least in the genus Haplognathia, jaw teeth that are visible by conventional light microscopy are composed of the same aggregated needle‐like denticles that are found, often in large numbers, on the basal plates of many filospermoid species. 2) Other new ultrastructural tooth features include the tricuspid basal plate teeth in Problognathia minima, tripartite teeth in Austrognathia and Austrognatharia, and the clear separation, in the Gnathostomula basal plate, of a mediodorsal set of teeth from a more extensive rostroventral set. 3) Three rows of teeth, as typical for Gnathostomulidae and Austrognathiidae, are also present in the filospermoid Haplognathia filum. 4) The wide range of geographic variation in Haplognathia ruberrima is confirmed by significant differences in jaw teeth between specimens from Belize and Bermuda. 5) A compartmentalized involucrum is present in Labidgonathia longicollis. 6) A pair of lamellae addentales, until now only known from Valvognathia pogonostoma, was found in Tenuignathia rikerae, Problognathia minima, and probably also Labidognathia rikerae. 7) In all gnathostomulids, the lamella symphysis is composed of identical rods that are considered homologous with those in the mouth parts of Rotifera and Micrognathozoa. J. Morphol. 253:310–334, 2002. © 2002 Wiley‐Liss, Inc.
Analysis of the interaction between the aspartic peptidase inhibitor SQAPI and aspartic peptidases using surface plasmon resonance
Authors: Farley Peter C. , Christeller John T. , Sullivan Michelle E. , Sullivan Patrick A. , Laing William A.
Published: October 2002

Aspartic peptidase inhibitors, which are themselves proteins, are strong inhibitors (small inhibition constants) of some aspartic peptidases but not others. However, there have been no studies of the kinetics of the interaction between a proteinaceous aspartic peptidase inhibitor and aspartic peptidases. This paper describes an analysis of rate constants for the interaction between recombinant squash aspartic peptidase inhibitor (rSQAPI) and a panel of aspartic peptidases that have a range of inhibition constants for SQAPI. Purified rSQAPI completely inhibits pepsin at a 1:1 molar ratio of pepsin to rSQAPI monomer (inhibition constant 1 nM). The interaction of pepsin with immobilized rSQAPI, at pH values between 3.0 and 6.0, was monitored using surface plasmon resonance. Binding of pepsin to rSQAPI was slow (association rate constants ca 104M
−1s−1), but rSQAPI was an effective pepsin inhibitor because dissociation of the rSQAPI‐pepsin complex was much slower (dissociation rate constants ca 10−4s−1), especially at low pH values. Similar results were obtained with a His‐tagged rSQAPI. Strong inhibition (inhibition constant 3 nM) of one isoform (rSap4) of the family of Candida albicans‐secreted aspartic peptidases was, as with pepsin, characterized by slow binding of rSap4 and slower dissociation of the rSap4‐inhibitor complex. In contrast, weaker inhibition of the Glomerella cingulata‐secreted aspartic peptidase (inhibition constant 7 nM) and the C. albicans rSap1 and Sap2 isoenzymes (inhibition constants 25 and 400 nM, respectively) was, in each case, characterized by a larger dissociation rate constant. Copyright © 2002 John Wiley & Sons, Ltd.
Differentiation of clinically benign and malignant breast lesions using diffusion‐weighted imaging
Authors: Guo Yong , Cai You‐Quan , Cai Zu‐Long , Gao Yuan‐Gui , An Ning‐Yu , Ma Lin , Mahankali Srikanth , Gao Jia‐Hong
Published: October 2002

Purpose

To evaluate the value of diffusion‐weighted imaging (DWI) in distinguishing between benign and malignant breast lesions.

Materials and Methods

Fifty‐two female subjects (mean age = 58 years, age range = 25–75 years) with histopathologically proven breast lesions underwent DWI of the breasts with a single‐shot echo‐planar imaging (EPI) sequence using large b values. The computed mean apparent diffusion coefficients (ADCs) of the breast lesions and cell density were then correlated.

Results

The ADCs varied substantially between benign breast lesions ((1.57 ± 0.23) × 10−3 mm2/second) and malignant breast lesions ((0.97 ± 0.20) × 10−3 mm2/second). In addition, the mean ADCs of the breast lesions correlated well with tumor cellularity (P < 0.01, r = −0.542).

Conclusion

The ADC would be an effective parameter in distinguishing between malignant and benign breast lesions. Further, tumor cellularity has a significant influence on the ADCs obtained in both benign and malignant breast tumors. J. Magn. Reson. Imaging 2002;16:172–178. © 2002 Wiley‐Liss, Inc.
Silylation of an OH‐terminated self‐assembled monolayer surface through low‐energy collisions of ions: a novel route to synthesis and patterning of surfaces
Authors: Wade Nathan , Evans Chris , Jo Sung‐Chan , Cooks R. Graham
Published: October 2002

Using a multi‐sector ion–surface scattering mass spectrometer, reagent ions of the general form SiR3+ were mass and energy selected and then made to collide with a hydroxy‐terminated self‐assembled monolayer (HO‐SAM) surface at energies of ∼15 eV. These ion–surface interactions result in covalent transformation of the terminal hydroxy groups at the surface into the corresponding silyl ethers due to Si—O bond formation. The modified surface was characterized in situ by chemical sputtering, a low‐energy ion–surface scattering experiment. These data indicate that the ion–surface reactions have high yields (i.e. surface reactants converted to products). Surface reactions with Si(OCH3)3+, followed by chemical sputtering using CF3+, yielded the reagent ion, Si(OCH3)3+, and several of its fragments. Other sputtered ions, namely SiH(OCH3)2OH2+ and SiH2(OCH3)OH2+, contain the newly formed Si—O bond and provide direct evidence for the covalent modification reaction. Chemical sputtering of modified surfaces, performed using CF3+, was evaluated over a range of collision energies. The results showed that the energy transferred to the sputtered ions, as measured by their extent of fragmentation in the scattered ion mass spectra, was essentially independent of the collision energy of the projectile, thus pointing to the occurrence of reactive sputtering.

A set of silyl cations, including SiBr3+, Si(C2H3)3+ and Si(CH3)2F+, were similarly used to modify the HO‐SAM surface at low collision energies. A reaction mechanism consisting of direct electrophilic attack by the cationic projectiles is supported by evidence of increased reactivity for these reagent ions with increases in the calculated positive charge at the electron‐deficient silicon atom of each of these cations. In a sequential set of reactions, 12 eV deuterated trimethylsilyl cations, Si(CD3)3+, were used first as the reagent ions to modify covalently a HO‐SAM surface. Subsequently, 70 eV SiCl3+ ions were used to modify the surface further. In addition to yielding sputtered ions of the modified surface, SiCl3+ reacted with both modified and unmodified groups on the surface, giving rise not only to such scattered product ions as SiCl2OH+ and SiCl2H+, but also to SiCl2CD3+ and SiCl2D+. This result demonstrates that selective, multi‐step reactions can be performed at a surface through low‐energy ionic collisions. Such processes are potentially useful for the construction of novel surfaces from a monolayer substrate and for chemical patterning of surfaces with functional groups. Copyright © 2002 John Wiley & Sons, Ltd.
Complexes of bivalent metal cations in electrospray mass spectra of common organic compounds
Authors: Bieńkowski Tomasz , Brodzik‐Bieńkowska Agnieszka , Danikiewicz Witold
Published: October 2002

In the standard electrospray ionization mass spectra of many common, low molecular mass organic compounds dissolved in methanol, peaks corresponding to ions with formula [3M + Met]2+ (M = organic molecule, Met = bivalent metal cation) are observed, sometimes with significant abundances. The most common are ions containing Mg2+, Ca2+ and Fe2+. Their presence can be easily rationalized on the basis of typical organic reaction work‐up procedures. The formation of [3M + Met]2+ ions has been studied using N‐FMOC‐proline methyl ester as a model organic ligand and Mg2+, Ca2+, Sr2+, Ba2+, Fe2+, Ni2+, Mn2+, Co2+ and Zn2+ chlorides or acetates as the sources of bivalent cation. It was found that all ions studied form [3M + Met]2+ complexes with N‐FMOC‐proline methyl ester, some of them at very low concentrations. Transition metal cations generally show higher complexation activity in comparison with alkaline earth metal cations. They are also more specific in the formation of [3M + Met]2+ complexes. In the case of alkaline earth metal cations [2M + Met]2+ and [4M + Met]2+ complex ions are also observed. It has been found that [3M + Met]2+ complex ions undergo specific fragmentation at relatively low energy, yielding fluorenylmethyl cation as a major product. [M + Na]+ ions are much more stable and their fragmentation is not as specific. Copyright © 2002 John Wiley & Sons, Ltd.
Seroprevalence and determinants of herpes simplex type 2 infection in an STD clinic in Milan, Italy
Authors: Suligoi Barbara , Calistri Arianna , Cusini Marco , Palù Giorgio ,   the Italian Herpes Management Forum
Published: October 2002

A number of studies have shown that the seroprevalence of herpes simplex virus type 2 (HSV‐2) is higher among persons attending clinics for sexually transmitted diseases (STD) than among the general population. The HSV‐2 seroprevalence among STD patients, however, varies greatly among studies, possibly reflecting differences in the baseline prevalence of the infection among different general populations or in the distribution of risk factors. A cross‐sectional study was carried out to determine the seroprevalence of and the risk factors for HSV‐2 infection among 776 HIV‐negative persons attending an STD clinic in Milan, Italy. All samples were tested with a commercial HSV type‐2 specific gG ELISA test. The HSV‐2 seroprevalence was 29.5% (95% CI: 26.3–32.7%). The seroprevalence increased with age, yet it did not differ by gender. Among persons with a current STD, the seroprevalence was 44.3%. At the multivariate analysis, older age was independently associated with HSV‐2 infection. A self‐reported history of genital herpes was predictive of HSV‐2 infection. The agreement between history of genital herpes and HSV‐2 seroprevalence was poor, however, stressing that in clinical practice, caution should be used in interpreting the presence or absence of a history of genital herpes as an indicator of the presence or absence of HSV‐2 infection. Our data show that HSV‐2 seroprevalence among persons attending an STD clinic in Italy is high; thus serological screening for HSV‐2 might be advisable for STD patients. J. Med Virol. 67:345–348, 2002. © 2002 Wiley‐Liss, Inc.
Comparison of the efficacy of lamivudine and famciclovir in Asian patients with chronic hepatitis B: Results of 24 weeks of therapy
Authors: Lai Ching‐Lung , Yuen Man‐Fung , Hui Chee‐Kin , Garrido‐Lestache Silvia , Cheng Charles Tze‐Kin , Lai Yim‐Ping
Published: October 2002

Lamivudine therapy improves hepatic necro‐inflammatory activity, decreases progression of fibrosis, and suppresses hepatitis B virus (HBV) replication. Famciclovir has also been shown to have some effect in the suppression of HBV replication. The aim of the study was to compare the effect of treatment with lamivudine and famciclovir on serum HBV DNA levels in patients with chronic hepatitis B and to assess safety. A prospective randomised clinical study was carried out on 100 patients with chronic hepatitis B infection (50 patients received lamivudine 100 mg daily and 50 patients received famciclovir 500 mg three times a day for 12 weeks. From the twelfth week onwards, patients were offered lamivudine 100 mg daily up to 48 weeks). Significantly more patients treated by lamivudine than by famciclovir had undetectable HBV DNA levels after 12 weeks of therapy (P< 0.001). The median HBV DNA levels were significantly lower in the lamivudine‐treated patients from the second week of treatment onwards (P< 0.001 for all time points up to 12 weeks). At week 16, 4 weeks after the famciclovir treated patients were put on lamivudine, there was no longer any difference in HBV DNA levels between the two groups of patients. Both treatments were well tolerated and no serious adverse events were reported. It was concluded that in Chinese patients with chronic hepatitis B infection, lamivudine achieved effective suppression of HBV DNA levels within 4 weeks of therapy whereas famciclovir had a significantly weaker action. J. Med Virol. 67:334–338, 2002. © 2002 Wiley‐Liss, Inc.
Role for mucosal immune responses and cell‐mediated immune functions in protection from airborne challenge with Venezuelan equine encephalitis virus*
Authors: Elvin Stephen J. , Bennett Alice M. , Phillpotts Robert J.
Published: October 2002

Venezuelan equine encephalitis virus (VEEV) replicates in lymphoid tissues following peripheral inoculation and a high titre viraemia develops. Encephalitis develops after the virus enters the central nervous system from the blood, with the earliest neuronal involvement being via the olfactory nerve. Following aerosol challenge with virulent VEEV, the virus is thought to replicate in the nasal mucosa and there could be direct entry into the olfactory nerve via infected neuroepithelial cells. Protection from VEEV infection is believed to be primarily mediated by virus specific antibody. The correlation between protection and neutralising serum antibody titres is, however, inconsistent when the virulent virus is administered by the airborne route. This study demonstrates a link between antibody in serum and the nasal mucosa and protection by means of passive immunisation studies. Intra‐nasal administration of antibody increased protection against airborne virus in Balb/c mice. Vaccination of μMT strain mice that do not have functional B cells and cannot produce antibody revealed normal proliferation of spleen cells in vitro and robust cytokine production. Aerosol challenge of μMT mice demonstrated that complete protection was only achieved when passive immunisation with antibody was supplemented with active immunisation with the TC‐83 vaccine strain of the virus. This implies that cell‐mediated immune functions are required for protection against airborne challenge with virulent VEEV. J. Med Virol. 67:384–393, 2002. Copyright © Crown Copyright 2002. Recorded with the permission of the controller of Her Majesty's Stationery Office. Published by Wiley‐Liss, Inc.
Prophylaxis and treatment of influenza encephalitis in an experimental mouse model
Authors: Shinjoh Masayoshi , Yoshikawa Takashi , Li Yixing , Shiraishi Kyoko , Ueki Hideaki , Nerome Kuniaki
Published: October 2002

A mouse model study using mouse brain‐adapted influenza A virus was performed to establish the prophylaxis and treatment of influenza encephalitis and encephalopathy. All mice died after intranasal inoculation of the brain‐adapted influenza A virus (H7N3), and the pathological findings indicated the presence of significant encephalitis. Viral antigen was also detected in the brain, both pathologically and virologically. By contrast, infected mice immunized with inactivated vaccine of the same strain did not lose weight, which is an indicator of the overall condition of the mice, and all of them survived. Similarly, antiserum treatment in the early period (0–1 day post‐infection) resulted in 100% survival, and no pathological findings were observed in the brain. However, mice treated with antiserum 3 days post‐infection showed encephalitis with viral antigens in both glial cells and neurocytes. Although amantadine treatment for 4 days delayed weight loss, it did not prevent death from encephalitis. These results show vaccination and early antiserum treatment to be highly effective, whereas 4‐day treatment of amantadine was not very effective in treating or preventing influenza encephalitis. The life‐prolonging effect of amantadine, however, suggests that use of amantadine together with other treatments may inhibit the progression of encephalitis. J. Med. Virol. 67:406–417, 2002. © 2002 Wiley‐Liss, Inc.
Recent progress and new trends in the treatment of hepatitis B
Authors: Alberti Alfredo , Brunetto Maurizia Rossana , Colombo Massimo , Craxì Antonio
Published: October 2002

The annual rate of progression to cirrhosis in patients with chronic HBV is 0.4 to 14.2% and that of death 4 to 10%. HCC risk increases in parallel with the severity and duration of infection, with an annual incidence less than 0.5% in carriers and 6% in patients with cirrhosis. The main aim of antiviral therapy for chronic “wild‐type” HBV infection is to suppress viral replication before cirrhosis and HCC develop. Two drugs are approved: IFN alpha and lamivudine. IFN alpha is costly, has a narrow range of efficacy, safety, and tolerability. Lamivudine is active, cheaper, and better tolerated but has limited efficacy, being associated with increasing resistance and loss of clinical response in the long term. IFN may be the first choice treatment in HBeAg‐positive patients with a favourable profile and compensated liver disease. Patients with HBeAg‐negative active disease can benefit from 12–24 months IFN treatment if early response is observed. Lamivudine should be started only after considering the uncertainties about duration of therapy and risks of stopping it. In patients with slowly progressive liver disease, treatment is better postponed until effective combination regimens are available. Lamivudine is of paramount importance in end‐stage chronic liver disease to suppress HBV replication and allow successful transplantation. The role of interferon in preventing HCC is controversial. In two studies comparing the incidence of HCC in patients with HBeAg‐negative chronic hepatitis treated with IFN, HCC developed less frequently in sustained responders than in non‐responders in Greece (2 vs. 10%, P = 0.045), but not in Milan (7 vs. 10%, P = ns). J. Med. Virol. 67:458–462, 2002. © 2002 Wiley‐Liss, Inc.
Progress in the prevention and control of viral hepatitis type B: Closing remarks
Authors: Rizzetto Mario , Zanetti Alessandro R.
Published: October 2002

Hepatitis type B remains an important disease globally. Rapid advances have been made during the last two decades in the understanding of the biology of HBV, the complex interaction between the virus and the host, and the pathology and the clinical aspects of infection. Mass vaccination has been shown to be a safe and highly effective means for the control and prevention of hepatitis B. The presence of a large worldwide reservoir of carriers requires a continuous effort to develop new drugs for the treatment of persistent HBV infection. Efforts to sustain immunization programs and to make vaccines and drugs available to countries with limited resources, are the main challenges to the eradication of hepatitis B in the next few decades. J. Med. Virol. 67:463–466, 2002. © 2002 Wiley‐Liss, Inc.
Systemic and intestinal antibody responses to NSP4 enterotoxin of Wa human rotavirus in a gnotobiotic pig model of human rotavirus disease
Authors: Iosef Cristiana , Chang Kyeong‐Ok , Azevedo Marli S.P. , Saif Linda J.
Published: October 2002

Antibody responses to the Wa human rotavirus (HRV) nonstructural protein NSP4, a viral enterotoxin, were evaluated in neonatal gnotobiotic (Gn) pigs. Gn pigs were inoculated orally with one dose of 105 fluorescent focus units (FFU) of virulent Wa HRV (HRV‐V), to mimic natural infection, or with three doses of 5 × 107 FFU attenuated Wa HRV (HRV‐A) at 10‐day intervals, to mimic oral attenuated rotavirus vaccines, or they were mock inoculated (mock). Subsets of pigs were challenged with 106 FFU of virulent Wa HRV at post‐inoculation day 28 (PID 28). Post‐challenge, the HRV‐V pigs were completely protected against diarrhea and virus shedding, whereas the HRV‐A pigs had a 50% protection rate against diarrhea and a 67% protection rate against virus shedding. All mock‐inoculated pigs shed virus and had diarrhea post‐challenge. Isotype antibody titers to NSP4 were compared in serum and intestinal contents, at post‐inoculation day (PID) 28 and at post‐challenge day 7 (PCD 7/PID 35) by indirect ELISA, using purified recombinant NH2‐6xHis‐tagged NSP4 of virulent Wa HRV. Pre‐challenge, both the HRV‐V and HRV‐A‐inoculated pigs had similar moderate titers of serum IgG antibodies to NSP4. However, only the HRV‐V‐inoculated pigs developed detectable serum and intestinal IgA antibody titers to NSP4 pre‐challenge, compared with the HRV‐A‐inoculated pigs. The mock‐inoculated pigs had no IgM, IgA, or IgG antibodies to NSP4 pre‐challenge. All Wa HRV‐inoculated pigs developed low to moderate titers of serum IgM, IgG, and IgA antibodies to NSP4 post‐challenge, but the mock‐inoculated pigs had only IgM antibodies post‐challenge. Both Wa HRV‐inoculated groups developed low titers of IgA antibody to NSP4 in the small intestinal contents post‐challenge, but titers were 5.8‐fold higher in the HRV‐V pigs. Our results concur with findings that both rotavirus vaccinated and naturally infected children seroconvert with modest IgG antibodies to NSP4 [Johansen et al. (1999) J Med Virol 59:369–367]. These data suggest that Gn pigs could be a useful model to evaluate serum and intestinal IgA antibodies to NSP4 and their role in protection against HRV infection. Further experiments may clarify whether (1) the NSP4 antibodies detected pre‐challenge in the HRV‐V pigs contribute to the higher protection rates observed, or (2) the reduced or delayed NSP4 antibody responses of the HRV‐A pigs are associated with the lower protection rates in these pigs. J. Med. Virol. 68:119–128, 2002. © 2002 Wiley‐Liss, Inc.
HBV subtype as a marker of the clinical course of chronic HBV infection in Japanese patients
Authors: Sakai Takahisa , Shiraki Katsuya , Inoue Hidekazu , Okano Hiroshi , Deguchi Masatoshi , Sugimoto Kazushi , Ohmori Shigeru , Murata Kazumoto , Fujioka Hiromichi , Takase Koujirou , Tameda Yukihiko , Nakano Takeshi
Published: October 2002

Hepatitis B virus (HBV) genotype C is predominant in Japan. However, many HBV subtypes are involved in each genotype, and the clinical manifestations in the patients associated with each subtype remain unknown. Therefore, we investigated the relationship between HBV subtype and clinical aspects of chronic HBV infection. The subtype of 237 patients with chronic HBV infection, including 74 asymptomatic carriers, was determined. The subtypes of 110 HBV carriers undergoing long‐term follow‐up management were determined twice to detect subtypic changes. The clinical features of the patients were also studied with regard to presence or absence of subtypic change. The subtypic distribution in the 237 HBV carriers was as follows: subtype adr, 161 (68%); subtype adw, 25 (11%); subtype adwr, 12 (5%); subtype ar, 24 (10%); subtype adyr, 4 (2%); and unclassified, 8 (3%). The proportion of asymptomatic carriers in patients with subtype adw was significantly higher than those in patients with subtype adr (56% vs. 28%, P < 0.05). In addition, the proportion of HCC in patients with subtype adwr was significantly higher than those in patients with subtype adr (25% vs. 6%, P < 0.05). The prevalence of subtype adr in 74 asymptomatic carriers tended to decrease with age (82% in carriers aged ≤35 years vs 43% in those aged ≥61 years, P < 0.05). The subtypic change and the course of chronic HBV infection had no significant correlation. These results suggest that HBV subtypes are associated with the clinical course of chronic HBV infection. J. Med. Virol. 68: 175–181, 2002. © 2002 Wiley‐Liss, Inc.
Susceptibility of diverse primary HIV isolates with varying co‐receptor specificity's to CXCR4 antagonistic compounds
Authors: Owen Sherry M. , Rudolph Donna , Schols Dominique , Fujii Nobutaka , Yamamoto Naoki , Lal Renu B.
Published: October 2002

The chemokine receptors CCR5 and CXCR4 are an obvious target for HIV therapies. Two compounds, T‐22 and AMD‐3100, have been shown to inhibit infection of CXCR4‐using HIV‐1 isolates. The specificity of T‐22 and AMD‐3100 was further confirmed by their ability to block entry of HIV‐1 in GHOST‐CXCR4 transfected cells with no effect on viral entry in the GHOST‐CCR5 cells. The ability of T‐22 to block replication of diverse HIV‐1 isolates (group M, subtypes A, B, D, E, and F as well as group O) and HIV‐2 primary isolates with varying coreceptor specificities ranging from exclusive CCR5 usage to multiple coreceptor usage was examined in detail. T‐22 was found to be highly effective (>90%) at blocking infection of diverse HIV‐1 (subtypes A–F, and group O) and HIV‐2 isolates that use multiple coreceptors in human PBMCs homozygous for a 32‐bp deletion in CCR5 (CCR5−/−), but less effective in CCR5 +/+ PBMCs. Additionally, sequential primary HIV‐1 isolates obtained from a longitudinal cohort who had switched from single coreceptor usage to a broad range of multiple receptors could be blocked effectively by both T‐22 and AMD‐3100 in CCR5−/− PBMCs. Our data suggest that CXCR4 antagonistic compounds are highly effective in blocking the entry of X4‐tropic HIV‐1, and that these compounds could be a useful additive to current anti‐retroviral therapy for clinical management of HIV disease. J. Med. Virol. 68: 147–155, 2002. © 2002 Wiley‐Liss, Inc.
Genetic heterogeneity of the envelope 2 gene and eradication of hepatitis C virus after a second course of interferon‐α
Authors: Boulestin Anne , Sandres‐Sauné Karine , Payen Jean‐Louis , Alric Laurent , Dubois Martine , Pasquier Christophe , Vinel Jean‐Pierre , Pascal Jean‐Pierre , Puel Jacqueline , Izopet Jacques
Published: October 2002

The heterogeneity of the envelope 2 (E2) gene of the hepatitis C virus (HCV) was involved in the sensitivity of HCV to interferon‐α (IFN‐α). To assess the factors leading to virus eradication by IFN‐α, patients whose first treatment by IFN‐α failed and who had virus eradication after a second treatment were studied. These patients were paired with subjects in whom both treatments failed. The phosphorylation homology domain of the E2 gene (E2‐PHD) had no sequence variation between the two stages in both groups of patients. Therefore, this region has no clinical predictive value within a specific genotype. The hypervariable region 1 (HVR1) was analyzed by cloning and sequencing 20 clones per sample. Comparison of samples showed that the change in quasispecies induced by the first IFN‐α therapy could be associated with virus elimination obtained after a second treatment. The greater proportion of nonsynonymous mutations that was noted before the second treatment in responders suggest that pretherapeutic immune response is a major factor determining virus elimination and that the immune status of these patients changed between the first and the second treatment. J. Med. Virol. 68:221–228, 2002. © 2002 Wiley‐Liss, Inc.
Performance of adaptive dual‐dropping ILUT preconditioners in semiconductor dopant diffusion simulation
Authors: Zhang Jun , Pardhanani Anand L. , Carey Graham F.
Published: October 2002

Preconditioning strategies based on incomplete LU factorization using thresholding with dual dropping (ILUT) are investigated for iterative solution of sparse linear systems arising in semiconductor dopant diffusion modelling. Of particular interest are questions associated with selection and adaption of threshold parameters with spatial resolution, timestep in the adaptive ODE integrator and the problem physics. We investigate these issues and carry out detailed numerical studies in one‐ and two‐dimensions for a representative phosphorus diffusion model. Guidelines for optimally selecting the threshold parameters are deduced from the results, and strategies for adaptive parameter selection are presented. Copyright © 2002 John Wiley & Sons, Ltd.
The finite element modelling of laser soldering for electronic assemblies
Authors: Beckett P. M. , Fleming A. R. , Gilbert J. M. , Whitehead D. G.
Published: October 2002

The laser provides a controllable means of supplying localized energy for solder joint formation and is a valuable tool in electronics manufacture. The modelling of heating behaviour in typical structures requires consideration of many different phenomena and the resulting models can become complex. The work described here shows that, given appropriate modelling assumptions, finite element models are able to give accurate predictions of heating in high‐pin count devices as well as a valuable insight into the important factors affecting the success of laser soldering operations. In particular, it is shown here that conduction through the body of the component being soldered does not significantly affect heating of the solder but that variations in copper track thickness can result in a doubling of the required soldering time. In addition, it is shown that conduction through the printed circuit board is important when using a scanned laser beam to solder multiple joints. Copyright © 2002 John Wiley & Sons, Ltd.
Full‐wave modelling of microstrip line and its sensitivities on lossy multilayer dielectric substrate and superstrate with laminated ground plane
Authors: Mayouf A. , Djahli F. , Mayouf F.
Published: October 2002

This paper presents a new formulation useful for modelling multilayered microstrip and its geometrical sensitivities with laminated ground plane. New integral equations are formulated, in the spectral domain, using the exact dyadic Green's function of bianisotropic planar media. We have applied a dynamic two‐dimensional least‐square algorithm as an optimization procedure. Obtained results agree well with those of other approaches. Copyright © 2002 John Wiley & Sons, Ltd.
Influence of cell density and thyroid hormone on glial cell development in primary cultures of embryonic rat cerebral hemisphere
Authors: Adachi Tatsumi , Takanaga Hiromi , Sakurai Yoko , Ishido Masami , Kunimoto Manabu , Asou Hiroaki
Published: October 2002

The influence of cell density and thyroid hormone (TH) on the development of astrocytes and oligodendrocytes was investigated in primary cultures prepared from rat cerebral hemisphere on embryonic day (E)18. At the beginning of the culture, most of the cells were microtubule‐associated protein 2 (MAP2)‐positive neurons, whereas O1‐positive oligodendrocytes and glial fibrillary acidic protein (GFAP)‐positive astrocytes were rarely observed. After the cells were maintained in serum‐free defined medium, astrocytes developed at high cell density but rarely at a low one. When leukemia inhibitory factor (LIF) was supplemented in low‐density cultures, the levels of GFAP expression markedly increased to almost the same extent as in high‐density culture without TH. This suggests that, in low‐density cultures, astrocyte progenitors could not differentiate because of insufficient astrocyte‐inducing factors. Interestingly, the addition of TH increased GFAP expression levels only at high density. The number of oligodendrocytes increased with TH addition at both cell densities, although the effects were more remarkable at high density. These results suggest that cell density and TH are pivotal factors in the development of both astrocytes and oligodendrocytes. It is also suggested that the effects of TH on glial cell development could be accelerated via cell–cell communications. © 2002 Wiley‐Liss, Inc.
Glutathione release from cultured brain cells: Multidrug resistance protein 1 mediates the release of GSH from rat astroglial cells
Authors: Hirrlinger Johannes , Schulz Jörg B. , Dringen Ralf
Published: October 2002

To investigate the release of glutathione (GSH) from brain cells, cultures enriched for astroglial cells, neurons, oligodendroglial cells, and microglial cells derived from rat brain were studied. During incubation of astroglial cultures, GSH accumulated in the medium with a rate of 3.1 ± 0.6 nmol × h−1 × mg protein−1. In contrast, only marginal amounts of extracellular GSH were detectable in the media of the other brain cell cultures investigated. The mechanism of GSH release from astroglial cells, as yet, has not been reported. Multidrug resistance protein 1 (Mrp1), a transport protein known to mediate cellular export of glutathione disulfide and glutathione conjugates, is expressed in astroglial cultures. Inhibitors of Mrp1 were used to test for a function of this transporter in mediating GSH release from astroglial cells. The presence of the competitive Mrp1 inhibitor MK571 at a concentration of 50 μM inhibited the rate of GSH release by 63%. In contrast, the low concentration of 1 μM of MK571 increased the rate of GSH release by 83%. This bimodal concentration‐dependent effect of MK571 is in accord with literature data for the effects of Mrp1 substrates on GSH release from cells. In addition, the presence of cyclosporin A (10 μM) reduced the GSH release rate significantly and completely blocked the stimulating effect of 1 μM MK571 on the release of GSH from astroglial cells. In conclusion, the data presented are a strong indication that Mrp1 participates in the release of GSH from astroglial cells. © 2002 Wiley‐Liss, Inc.
Extra Raman modes in CdS during cubic to hexagonal structural transformation
Authors: Lozada‐Morales R. , Zelaya‐Angel O. , Jiménez‐Sandoval S. , Torres‐Delgado G.
Published: October 2002

Cubic CdS thin films were grown on glass substrates by chemical bath deposition at 80 °C. By means of thermal annealing (TA) in an Ar + S2 atmosphere in the 224–403 °C range, the cubic metastable zinc blende (ZB) crystalline structure gradually transforms to the stable wurtzite (W) phase. The critical temperature of this phase transformation is around 300 °C, where the material passes from a ZB‐dominated to a W‐dominated phase. Raman spectra obtained at room temperature in parallel and crossed polarizations exhibit extra vibrational modes only when TA is at 344 °C. These experimental findings were explained by considering the critical density of interstitially located Cd2+ ions and their influence to the lattice dynamics of the system. We assumed a model in which the interatomic bonds in the CdS lattice are physically described by a set of springs obeying Hooke's law. The calculated wavenumbers agree remarkably well with the experimental data considering the simplicity of the approach. Copyright © 2002 John Wiley & Sons, Ltd.
Formation mechanism of acetaldehyde lithium enolate by reaction of n‐butyllithium with tetrahydrofuran: infrared and Raman spectroscopy and density functional theory calculations
Authors: Corset Jacques , Castellà‐Ventura Martine , Froment Françoise , Strzalko Tekla , Wartski Lya
Published: October 2002

Depending on the reaction conditions, n‐butyllithium (n‐BuLi), as a base, may react both with the reactants and with the solvent. Thus, it has been shown that the n‐BuLi dimer reacts with tetrahydrofuran (THF) to give acetaldehyde lithium enolate (CH2CHOLi). The density functional theory approach at the B3‐LYP level with the 6–31 + G* basis set is applied to determine the geometrical, energetic and vibrational characteristics of the different aggregates of the acetaldehyde lithium enolate involved in the cleavage of THF by n‐BuLi. Calculations show that two types of anions may be distinguished in these aggregates, the O and π(CC)—Li bound one (pyramidal structure) and the only O—Li bound one (linear structure). In parallel, infrared (IR) and Fourier transform Raman spectroscopy allow one to determine the vibrational properties of the different enolate aggregates and to specify the mechanism of the THF cleavage. First, the n‐BuLi dimer reacts with a solvating THF molecule, leading to a reaction intermediate, the mixed aggregate (CH2CHOLi, n‐BuLi). Then, this aggregate reacts with a second solvating THF molecule, giving rise to the trans linear–linear enolate dimer, which further dimerizes to form a tetramer. The very good agreement between theory and experiment concerning the wavenumbers and the IR intensities allows one to validate the calculated structures of the different enolate aggregates. Copyright © 2002 John Wiley & Sons, Ltd.