bluuebunny/crossref_metadata_2025 huggingface dataset:
Dissection of Human Immunodeficiency Virus Type 1 Entry with Neutralizing Antibodies to gp41 Fusion Intermediates
Authors: Golding Hana , Zaitseva Marina , de Rosny Eve , King Lisa R. , Manischewitz Jody , Sidorov Igor , Gorny Miroslaw K. , Zolla-Pazner Susan , Dimitrov Dimiter S. , Weiss Carol D.
Published: July 2002

Human immunodeficiency virus type 1 (HIV-1) entry requires conformational changes in the transmembrane subunit (gp41) of the envelope glycoprotein (Env) involving transient fusion intermediates that contain exposed coiled-coil (prehairpin) and six-helix bundle structures. We investigated the HIV-1 entry mechanism and the potential of antibodies targeting fusion intermediates to block Env-mediated membrane fusion. Suboptimal temperature (31.5°C) was used to prolong fusion intermediates as monitored by confocal microscopy. After transfer to 37°C, these fusion intermediates progressed to syncytium formation with enhanced kinetics compared with effector-target (E/T) cell mixtures that were incubated only at 37°C. gp41 peptides DP-178, DP-107, and IQN17 blocked fusion more efficiently (5- to 10-fold-lower 50% inhibitory dose values) when added to E/T cells at the suboptimal temperature prior to transfer to 37°C. Rabbit antibodies against peptides modeling the N-heptad repeat or the six-helix bundle of gp41 blocked fusion and viral infection at 37°C only if preincubated with E/T cells at the suboptimal temperature. Similar fusion inhibition was observed with human six-helix bundle-specific monoclonal antibodies. Our data demonstrate that antibodies targeting gp41 fusion intermediates are able to bind to gp41 and arrest fusion. They also indicate that six-helix bundles can form prior to fusion and that the lag time before fusion occurs may include the time needed to accumulate preformed six-helix bundles at the fusion site.
Mapping the Transcription and Replication Promoters of Respiratory Syncytial Virus
Authors: Fearns Rachel , Peeples Mark E. , Collins Peter L.
Published: July 2002

An important, unresolved issue in mononegavirus biology is whether or not transcription is initiated by the same promoter as RNA replication. In this study, residues important for respiratory syncytial virus (RSV) transcription and RNA replication were identified by subjecting the first 26 nucleotides of genome RNA to saturation mutagenesis. This analysis was performed using a genome analog that allowed transcription and RNA replication to be dissociated from each other and monitored as independent events in an intracellular assay. This analysis showed that nucleotides 3C, 5C, 8U, 9U, 10U, and 11U were important for transcription and RNA replication. Additional nucleotides (1U, 2G, 6U, and 7U) were important for RNA replication, but not transcription. At position 4, G versus C or U augmented transcription and decreased replication, showing that the naturally occurring assignments in the genomic (4G) and antigenomic (4U) promoters are optimal for transcription and RNA replication, respectively. These data show that RSV transcription and RNA replication each involve a
cis
-acting signal at the very 3" end of the genome. This signal appears to contain a minimum, common element that functions in both transcription and RNA replication, defined by those substitutions that had similar effects on the two processes. Apart from these common nucleotides, other positions were involved in RNA replication but not transcription or had different effects on the two processes. This indicates that the promoters for transcription and replication involve overlapping sets of nucleotides at the very 3" end of the genome and provides evidence that the nucleotide preferences for the two processes are not identical.
Evolution of a Human Immunodeficiency Virus Type 1 Variant with Enhanced Replication in Pig-Tailed Macaque Cells by DNA Shuffling
Authors: Pekrun Katja , Shibata Riri , Igarashi Tatsuhiko , Reed Margaret , Sheppard Liana , Patten Philip A. , Stemmer Willem P. C. , Martin Malcolm A. , Soong Nay-Wei
Published: July 2002

DNA shuffling facilitated the evolution of a human immunodeficiency virus type 1 (HIV-1) variant with enhanced replication in pig-tailed macaque peripheral blood mononuclear cells (pt mPBMC). This variant consists exclusively of HIV-1-derived sequences with the exception of simian immunodeficiency virus (SIV)
nef
. Sequences spanning the
gag
-protease-reverse transcriptase (
gag
-
pro
-RT) region from several HIV-1 isolates were shuffled and cloned into a parental HIV-1 backbone containing SIV
nef
. Neither this full-length parent nor any of the unshuffled HIV-1 isolates replicated appreciably or sustainably in pt mPBMC. Upon selection of the shuffled viral libraries by serial passaging in pt mPBMC, a species emerged which replicated at substantially higher levels (50 to 100 ng/ml p24) than any of the HIV-1 parents and most importantly, could be continuously passaged in pt mPBMC. The parental HIV-1 isolates, when selected similarly, became extinct. Analyses of full-length improved proviral clones indicate that multiple recombination events in the shuffled region and adaptive changes in the rest of the genome contributed synergistically to the improved phenotype. This improved variant may prove useful in establishing a pig-tailed macaque model of HIV-1 infection.
CD28−/−Mice Show Defects in Cellular and Humoral Immunity but Are Able To Control Infection with Murine Gammaherpesvirus 68
Authors: Lee Bong Joo , Reiter Su Khoh , Anderson Mandy , Sarawar Sally R.
Published: July 2002

The role of CD28-dependent costimulatory interactions in the development and maintenance of antiviral immune responses was investigated in a mouse model of gammaherpesvirus infection. CD28−/−mice could clear a productive infection with murine gammaherpesvirus 68 (MHV-68), although early lung viral titers were significantly increased. Both CD28−/−and CD28+/+mice maintained effective long-term control of MHV-68. Gamma interferon responses appeared to develop more slowly in CD28−/−mice, while cytotoxic T-cell activity was similar to that in wild-type mice. Splenomegaly developed normally in CD28−/−mice, whereas virus-specific antibody responses were significantly reduced and aberrant class switching was observed. This work demonstrates that costimulatory interactions involving CD28 are not an absolute requirement for the control of infection with MHV-68.
Open Reading Frame 50 Protein of Kaposi's Sarcoma-Associated Herpesvirus Directly Activates the Viral PAN and K12 Genes by Binding to Related Response Elements
Authors: Chang Pey-Jium , Shedd Duane , Gradoville Lyn , Cho Myung-Sam , Chen Lee-Wen , Chang Jimmy , Miller George
Published: July 2002

Open reading frame (ORF) 50 protein is capable of activating the entire lytic cycle of Kaposi's sarcoma-associated herpesvirus (KSHV), but its mechanism of action is not well characterized. Here we demonstrate that ORF 50 protein activates two KSHV lytic cycle genes, PAN (polyadenylated nuclear RNA) and K12, by binding to closely related response elements located approximately 60 to 100 nucleotides (nt) upstream of the start of transcription of the two genes. The 25-nt sequence 5′ AAATGGGTGGCTAACCTGTCCAAAA from the PAN promoter (PANp) confers a response to ORF 50 protein in both epithelial cells and B cells in the absence of other KSHV proteins. The responsive region of DNA can be transferred to a heterologous minimal promoter. Extensive point mutagenesis showed that a span of at least 20 nt is essential for a response to ORF 50 protein. However, a minimum of six positions within this region were ambiguous. The related 26-nt responsive element in the K12 promoter (K12p), 5′ GGAAATGGGTGGCTAACCCCTACATA, shares 20 nt (underlined) with the comparable region of PANp. The divergence is primarily at the 3′ end. The DNA binding domain of ORF 50 protein, encompassing amino acids 1 to 490, fused to a heterologous activation domain from herpes simplex virus VP16 [ORF 50(1-490)+VP] can mediate activation of reporter constructs bearing these response elements. Most importantly, ORF 50(1-490)+VP can induce PAN RNA and K12 transcripts in transfected cells. ORF 50(1-490)+VP expressed in human cells binds specifically to duplex oligonucleotides containing the responsive regions from PANp and K12p. These DNA-protein complexes were supershifted by antibody to VP16. ORF 50(1-490) without a VP16 tag also bound to the response element. There was a strong correlation between DNA binding by ORF 50 and transcriptional activation. Mutations within PANp and K12p that impaired transactivation by ORF 50 or ORF 50(1-490)+VP also abolished DNA binding. Only one of eight related complexes formed on PANp and K12p oligonucleotides was due to ORF 50(1-490)+VP. The other complexes were due to cellular proteins. Two KSHV lytic-cycle promoters are activated by a similar mechanism that involves direct recognition of a homologous response element by the DNA binding domain of ORF 50 protein in the context of related cellular proteins.
Anti-TAR Polyamide Nucleotide Analog Conjugated with a Membrane-Permeating Peptide Inhibits Human Immunodeficiency Virus Type 1 Production
Authors: Kaushik Neerja , Basu Amartya , Palumbo Paul , Myers Rene L. , Pandey Virendra N.
Published: July 2002

The emergence of drug-resistant variants has posed a significant setback against effective antiviral treatment for human immunodeficiency virus (HIV) infections. The choice of a nonmutable region of the viral genome such as the conserved transactivation response element (TAR element) in the 5′ long terminal repeat (LTR) may potentially be an effective target for drug development. We have earlier demonstrated that a polyamide nucleotide analog (PNA) targeted to the TAR hairpin element, when transfected into cells, can effectively inhibit Tat-mediated transactivation of HIV type 1 (HIV-1) LTR (T. Mayhood et al., Biochemistry 39:11532-11539, 2000). Here we show that this anti-TAR PNA (PNA
TAR
), upon conjugation with a membrane-permeating peptide vector (transportan) retained its affinity for TAR in vitro similar to the unconjugated analog. The conjugate was efficiently internalized into the cells when added to the culture medium. Examination of the functional efficacy of the PNA
TAR
-transportan conjugate in cell culture using luciferase reporter gene constructs resulted in a significant inhibition of Tat-mediated transactivation of HIV-1 LTR. Furthermore, PNA
TAR
-transportan conjugate substantially inhibited HIV-1 production in chronically HIV-1-infected H9 cells. The mechanism of this inhibition appeared to be regulated at the level of transcription. These results demonstrate the efficacy of PNA
TAR
-transportan as a potential anti-HIV agent.
A Study of Lead Sorption by a Cellulose-Based Chelating Ion Exchanger Ostsorb Dtta
Authors: Svoboda Ladislav , Chutný Jaroslav , Tomek Miloslav
Published: July 2002

Complexing properties of the chelating ion exchanger based on spherical cellulose modified by the functional groups of diethylenetriaminetetraacetic acid, Ostsorb DTTA, have been studied in the sorption of lead from aqueous medium at various experimental conditions, such as pH, the dynamic or static arrangement of experiment, the presence of other compounds, the concentration of the ion being sorbed, the form of ion exchanger etc. The results have been compared with the data found with the known selective ion exchanger Dowex A-1. Ostsorb DTTA exhibits good kinetics of the ion exchange at the exchange capacity of 210 mg Pb g-1 for pH 6. For some applications, its lower mechanical stability and high water content in the swollen particles may be unfavourable.
Low Temperature Sintering Studies of Ammonium Molybdate, Nickel Hydroxide and Nickel Molybdate
Authors: Halawy Samih A. , Abd El-Salaam Khalaf Alla M. , Ragih Hesham M.
Published: July 2002

The thermal decomposition of ammonium molybdate, nickel hydroxide and MoO3-NiO 50 mole % mixture were studied by means of TG and DTG non-isothermally, in a dynamic atmosphere of N2. The activation energy of the thermal process of such samples, also, were evaluated using Maple's theory, in isothermal condition. The variation of SBET with time, during heating ammonium molybdate, nickel hydroxide and MoO3-NiO 50 mole % mixture at different temperatures, in the range 200 - 400 °C, was monitored, and the activation energy for the sintering process of each compound were calculated from the Arrhenius plot. The final products of heating each sample at the sintering temperatures after 6 h, were characterized by IR and XRD analyses. MoO3 was formed clearly at 350 °C, while Ni forms a mixture of nickel(II) and -(III) oxides at the same temperature. NiMoO4 was produced, also, at 350 °C in MoO3-NiO 50 mole % mixture sample.
Application of a New Algorithm for Prediction and Modelling of Multiphase Behavior: A Case Study of Some Prototype Natural Gas Systems
Authors: Stateva Roumiana P. , Tsvetkov Stefan G.
Published: July 2002

The prediction and modelling are studied of complex multiphase behavior of four prototype ternary mixtures typically encountered in cryogenic processing of natural gases, with a new approach for solving the isothermal multiphase flash problem. The method includes a rigorous method for thermodynamic stability analysis as the first step and an efficient phase identification procedure as the second. The new algorithm provides an accurate global description of phase behavior of the studied LNG systems, and excellent agreement of the results obtained with experimental data.
7-Oxo-7a-oxa-brassinosteroids with Cholestane Side-Chain
Authors: Kohout Ladislav
Published: July 2002

New 7-oxo-7a-oxa analogs of brassinolide with cholestane side-chain were prepared. Analogs VIII and IX with 2,3-diol grouping exhibit a weak brassinolide activity. Of the synthesized compounds, the highest brassinolide activity was found for 3α,4α-dihydroxy-7a-oxa-B-homo-5α-cholestan-7-one (X).
The Synthesis of Heterocycles from Indolin-2-one Derivatives and Active Methylene Reagents
Authors: Abdel-Latif Fathy F. , Mekheimer Ramadan A. , Mashaly Mohamed M. , Ahmed Essam Kh.
Published: July 2002

Investigation the synthesis of multifunctionalized heterocyclic spiro derivatives via the reaction of isatin, ethyl cyanoacetate and an other active methylene compound. It has been found that refluxing of an ethanolic piperidine solution of equimolar ratios of isatin (Ia), ethyl cyanoacetate (II) and barbituric acid (IIIa) or thiobarbituric acid (IIIb) afforded a solid product whose structure was assumed, in accordance with elemental analysis and IR and 1H NMR spectra, to be VIIIa and VIIIb. Confirmation of the structures VIIIa and VIIIb follows from their preparation from compound IV, synthesized separately, and barbituric acids IIIa and IIIb in 1 : 1 molar ratio under the same reaction conditions.
Divalent Transition Metal Complexes of Potentially Polynucleating 8-Hydroxyquinoline-5-sulfonyl Hydrazone
Authors: Ibrahim Said A. , El-Gyar Sahar A. , Abdel-Hafez Aly A. , Rabia Mostafa K.
Published: July 2002

The Co(II), Ni(II), Cu(II) and Zn(II) complexes with 8-hydroxyquinoline-5-sulfonylhydrazone are described. It has been found that the ligand can coordinate to metal ion as a monobasic bidentate chelating agent and it can form di- and trinuclear complexes while acting as a dibasic tetradentate one. The structure of the isolated complexes have been suggested on the basis of elemental analysis, IR, 1H NMR spectroscopy and conductivity measurements. The complexes are all formulated as four-coordinate. Some complexes showed enhanced antimicrobial activity relative to the free ligand.
Spin-Orbit Coupling Induced Chemical Reactivity and Spin-Catalysis Phenomena
Authors: Minaev Boris F. , Ågren Hans
Published: July 2002

The crucial role of electron spin in the control of the reaction channels in the region of activated complexes can easily be inferred from the general principles of chemical bonding. Magnetic perturbations could change spin at the intermediate stages of a reaction or in the region of activation barriers and could hence influence the reaction rate through spin switching of the reaction paths. Spin-orbit coupling is one of the most important intrinsic magnetic perturbations in molecules; its role in chemical reactivity is here shown by a few typical examples. Spin-orbit coupling induced spin flip could also be important in catalysis by transition metals. General qualitative arguments predict great enhancements of the spin-orbit coupling in catalytic complexes with transition metal compounds. The concept of spin-catalysis is introduced in order to describe and classify a wide range of phenomena in which chemical reactions are promoted by substances assisting in inducing spin changes and overcoming spin-prohibition. This concept is based on results of quantum chemical calculations with account of spin-orbit coupling and configuration interaction in the intermediate complexes. Besides spin-orbit coupling, the role of intermolecular exchange interaction with open shell catalysts is stressed. The catalytic action would definitely depend on the efficiency of spin uncoupling inside the reacting substrate molecule and this could be induced by magnetic and exchange perturbations.
The Mixed Adsorption Layers of Butanol/Thiourea and Butanol/Toluidine at the Interface Hg/Aqueous Perchlorate Solution
Authors: Saba Jadwiga
Published: July 2002

Properties of mixed, two-component adsorption layers of butanol/thiourea, butanol/m-toluidine and butanol/p-toluidine in 1 M NaClO4 were investigated. The systems were characterized by the measurements of differential capacity, zero charge potential and surface tension at this potential. The data were analyzed to obtain the surface pressure and relative surface excess of thiourea, m-toluidine or p-toluidine as a function of charge and bulk concentration of these substances. The standard Gibbs energy of adsorption and parameters α, B obtained from the Frumkin and virial isotherms were compared. The electrostatic parameters of the inner layer were determined.
Adsorption and Diffusion in HZSM-5 Zeolite Studied by an Oscillating Microbalance
Authors: Rebo Hans P. , Chen De , Brownrigg Marit S. A. , Moljord Kjell , Holmen Anders
Published: July 2002

A novel microbalance technique has been used to study diffusion and adsorption in a commercial HZSM-5 zeolite. This new technique uses an inertial microbalance TEOM (Tapered Element Oscillating Microbalance) to measure mass changes in the zeolite bed. Time resolution as short as 0.1 s, a flow-through design where all the probe molecules see the zeolite bed and high sensitivity allowing zeolite loadings down to a few milligrams are the three most important properties of the TEOM. The probe molecules studied were o-xylene, p-xylene and toluene which were introduced at 303, 373 or 473 K and at partial pressures in the range of 0.2-10 kPa. The inverse characteristic uptakes (D/L2), corrected (D0/L2) and steady-state (Dss/L2) diffusion times are reported. The thermodynamic correction used for D0/L2 calculations almost eliminated the concentration dependence of the diffusivities. The Dss/L2 values were found to be rather unaffected by both temperature (373-473 K) and concentration, suggesting a certain degree of unification for diffusivities. o-Xylene uptake rates in the TEOM were found to be significantly higher than in a gravimetric microbalance under identical conditions, probably as a result of additional mass transfer resistance other than intracrystalline diffusion caused by poor contact between the gas phase and the zeolite in a conventional gravimetric microbalance.
Enantioselective Preparation of the Stereoisomersof 4-Methylheptan-3-ol Using Candida antarctica Lipase B
Authors: Unelius C. Rikard , Sandell Johan , Orrenius Christian
Published: July 2002

The four stereoisomers of 4-methylheptan-3-ol were prepared through fractional crystallization of a mixture of their racemic 4-methylhept-3-yl 3,5-dinitrobenzoates, followed by hydrolysis of each crystalline racemate and enantioselective, lipase-mediated transesterification of each pair of enantiomeric alcohols liberated, using the Candida antarctica lipase B as catalyst and S-ethyl octanethioate as the acyl donor. An analytical method of determining the enantiomeric composition of mixtures of 4-methyl-heptan-3-ols was developed. The optical purity of the separated isomers was in the range of 29-97%.
The Influence of N,N'-Dialkylthioureas on the Two-Step Electroreduction of Zn(II) Ions
Authors: Dalmata Grażyna
Published: July 2002

A two-step reduction of Zn(II) ions at the dropping mercury electrode in 1 M NaClO4/0.001 M HClO4 in the presence of N,N'-dialkylthioureas was examined in wide potential and frequency ranges, using the impedance method. The rate constant of the first electron transfer increases with increasing concentration of N,N'-dialkylthioureas, whereas that of the second electron transfer depends largely on the double layer effects, particularly, on the orientation of molecules on the electrode surface.
Probing Weakly-Bound Species with Nonresonant Light: Dissociation of He2Induced by Rotational Hybridization
Authors: Friedrich Břetislav , Gupta Manish , Herschbach Dudley
Published: July 2002

A field-dependent value of angular momentum can be imparted to a 4He2 cluster by the interaction of its anisotropic polarizability with a nonresonant laser field. In this way a centrifugal term is introduced that can be tuned to a critical value sufficient to overcome the potential that binds the dimer. Due to its dependence on the internuclear distance and laser intensity, the critical angular momentum for dissociation is attained at different internuclear separations for different pulsed-laser intensities. As a result, the dependence of the dissociation probability on the laser intensity offers a means to map the potential and/or the polarizability anisotropy. A comparison with experiment thus could provide a test of either. The technique is applicable to other molecules in bound states close to the dissociation limit.
From Intermolecular Interactions to Incipient Chemical Bond
Authors: Chałasiński Grzegorz , Klos Jacek , Cybulski Slawomir M. , Szczęśniak Małgorzata M.
Published: July 2002

The complexes of a rare gas atom (RG) and a number of open-shell molecules are discussed in the context of the bond character, structural and dynamical properties. The potential energy surfaces of a variety of complexes have been obtained using the combination of highly correlated supermolecular approach and the symmetry-adapted perturbation theory. Complexes of Σ-state species, O2 and NH, display typical non-covalent interactions, similar to closed-shell systems. Complexes of Π-state species are represented by pairs of adiabatic potentials A' and A'' due to removal of degeneracy through the interaction with the RG moiety. The two states may have distinctly different character. The He-CH(X2Π) complex displays an incipient π-bond on its A'' surface, while a regular van der Waals interaction is observed on the A' surface. Interaction of a Π-state chlorine atom with RG gives rise to two potential curves: Σ and Π. The Σ state features an incipient σ bond whereas the Π-state surface reveals a van der Waals interaction. The excited state complex He + Cl2(B3Πu) illustrates a different situation, with both the A' and A'' states fairly close to each other, with only slight indication of the incipient bond.
Removal of Anions from Solution by Calcined Hydrotalcite and Regeneration of Used Sorbent in Repeated Calcination-Rehydration-Anion Exchange Processes
Authors: Kovanda František , Kovácsová Eva , Koloušek David
Published: July 2002

Synthetic hydrotalcite calcined at 350-550 °C was used for the removal of arsenate, chromate, and vanadate ions from water solutions. The initial anion concentrations were 0.002 mol l-1. The sorption isotherms were measured at 20 °C and at neutral pH. The Langmuir adsorption isotherm was used for the sorption capacity evaluation. The ability of the calcined hydrotalcite to remove the anions from solution decreased in the order of vanadate - arsenate - chromate. The hydrotalcite calcined at 450 °C exhibited the best sorption ability for all the anions. The sorbed anions were released by anion exchange in a carbonate-containing solution and the hydrotalcite after subsequent calcination was used again for the removal of anions. The repeating cycles calcination-rehydration-anion exchange gradually reduced the adsorption capacity of the hydrotalcite. The sorption capacity decreased by 50% after the first two cycles but it did not change significantly in the subsequent cycles. When chromate anions were adsorbed, the decrease in sorption capacity was not observed during repeated calcination-rehydration-anion exchange cycles. The change in the sorption capacity was influenced by the ability of calcined hydrotalcite to regenerate the layered crystal structure during the rehydration process.
Dissociation of Naphthoic Acids in Non-Aqueous Media. Comparison of Benzene and Naphthalene Skeletons
Authors: Pařík Patrik , Wolfová Jitka , Ludwig Miroslav
Published: July 2002

Seven monosubstituted 1-naphthoic acids were synthesized by new or modified procedures, and their dissociation constants were measured potentiometrically at 25 °C in methanol, acetonitrile, dimethylformamide, and pyridine. Dissociation constants of these along with thirteen substituted 1-naphthoic acids and twenty-five substituted 2-naphthoic acids previously studied were measured at 25 °C in ethanol and dimethyl sulfoxide. The pKHAvalues of 3- and 4-substituted 1-naphthoic acids were treated by simple linear regression and principal component analysis, and the results were used for comparison of model compounds and of corresponding 3- and 4-substituted benzoic acids with the aim of comparison of benzene and naphthalene skeletons. It has been found, the 3 and 4 positions of the 1-naphthyl system can roughly be compared with themetaandparapositions of benzene, respectively.
Outer-Sphere Charge-Transfer Excitation in the Ion Pair [Co(NH3)6]3+[B12H12]2-
Authors: Kunkely Horst , Vogler Arnd
Published: July 2002

The aqueous ion pair [Co(NH3)6]3+[B12H12]2- displays an UV absorption at λmax = 250 nm which is assigned to an outer-sphere charge-transfer (OSCT) transition from [B12H12]2- to [Co(NH3)6]3+. OSCT excitation leads to photoredox reaction with the formation of Co2+ (Φ = 0.03 at λirr = 313 nm).
The 1H and 13C NMR Chemical Shift Assignments for Thirteen Bufadienolides Isolated from the Traditional Chinese Drug Ch'an Su
Authors: Kamano Yoshiaki , Nogawa Toshihiko , Yamashita Ayano , Pettit George R.
Published: July 2002

The 1H and 13C NMR spectra of thirteen natural bufadienolides, which were isolated from the Chinese drug Ch'an Su, were assigned using a combination of 2D NMR spectra that included 1H-1H COSY, NOESY, HMQC, and HMBC techniques.
Contact dermatitis in students practicing sports: incidence of rubber sensitisation
Authors: Ventura M T , Dagnello M , Matino M G , Di Corato R , Giuliano G , Tursi A
Published: July 2002

Background—Over the last few years, changes in cutaneous homoeostasis resulting from sports activities have been reported. In particular, alterations in sweating mechanisms, the hydrolipid barrier, and surface bacterial flora, together with exposure to atmospheric conditions and the need to use medicaments, detergents, and other topical substances, predispose subjects to allergic contact dermatitis.

Objective—To evaluate the incidence of allergic contact dermatitis in a group of young people practising sports activities.

Methods—Patch tests were performed to confirm the diagnosis of irritant or allergic dermatitis; in addition, the radioallergoabsorbent test (RAST) to latex was evaluated in the group studied.

Results—Allergic contact dermatitis caused by thiourams (23.3%) and mercaptobenzothiazole (20.9%) was prevalent. Other haptens, such as benzocaine and nickel, which are contained in clothing, equipment, topical medicaments, and creams used for massage, were also allergenic. In two cases, RAST positivity to latex was registered.

Conclusions—The results suggest that close contact with sports equipment may increase the incidence of allergic contact dermatitis. Students practising certain sports may have “professional” allergic contact dermatitis to additives used in the production of rubber.
The acute phase response and exercise: court and field sports
Authors: Fallon K E , Fallon S K , Boston T
Published: July 2002

Objective—To determine the presence or absence of an acute phase response after training for court and field sports.

Participants—All members of the Australian women's soccer team (n = 18) and all members of the Australian Institute of Sport netball team (n = 14).

Methods—Twelve acute phase reactants (white blood cell count, neutrophil count, platelet count, serum iron, ferritin, and transferrin, percentage transferrin saturation, α1antitrypsin, caeruloplasmin, α2acid glycoprotein, C reactive protein, and erythrocyte sedimentation rate) were measured during a rest period and after moderate and heavy training weeks in members of elite netball and women's soccer teams.

Results—Responses consistent with an acute phase response were found in five of 24 tests in the soccer players, and in three of 24 tests in the netball players. Responses in the opposite direction were found in seven of 24 tests in the soccer players and two of 24 tests in the netballers. The most sensitive reactant measured, C reactive protein, did not respond in a manner typical of an acute phase response.

Conclusion—An acute phase response does not seem to occur as a consequence of the levels of training typical of elite female netball and soccer teams. This has implications for the interpretation of biochemical variables in these groups.
Fatal methane and cyanide poisoning as a result of handling industrial fish: a case report and review of the literature
Authors: Cherian M A , Richmond I
Published: July 2002

The potential health hazards of handling industrial fish are well documented. Wet fish in storage consume oxygen and produce poisonous gases as they spoil. In addition to oxygen depletion, various noxious agents have been demonstrated in association with spoilage including carbon dioxide, sulphur dioxide, and ammonia. A fatal case of methane and cyanide poisoning among a group of deep sea trawler men is described. Subsequent independent investigation as a result of this case led to the discovery of cyanides as a further potential noxious agent. This is thus the first case in which cyanide poisoning has been recognised as a potentially fatal complication of handling spoiled fish. The previous literature is reviewed and the implications of the current case are discussed.
Wilson's disease: acute and presymptomatic laboratory diagnosis and monitoring
Authors: Gaffney D , Fell G S , O'Reilly D St J
Published: July 2002

Wilson's disease, the most common inherited disorder of copper metabolism, is a recessive genetic condition. The clinical presentation of Wilson's disease is very variable. It is characterised by low serum copper and caeruloplasmin concentrations coupled with the pathological accumulation of copper in the tissues. However, there are diagnostic difficulties and these are discussed. The current value of DNA diagnosis, both in gene tracking in families or as applied to de novo cases, is examined. Wilson's disease can be treated successfully but treatment must be life long. Patients are best treated by specialist centres with experience and expertise in the condition.
Pathogenesis of non-familial colorectal carcinomas with high microsatellite instability
Authors: Shitoh K , Konishi F , Miyaki M , Iijima T , Furukawa T , Tsukamoto T , Nagai H
Published: July 2002

Aims—Microsatellite instability (MSI) was first observed in hereditary non-polyposis colorectal carcinoma (HNPCC) and was subsequently seen in non-familial colorectal carcinoma. The relation between MSI and cancer associated genes in non-familial colorectal carcinomas has yet to be evaluated. To clarify this matter, changes in cancer associated genes were examined in non-familial colorectal carcinomas.

Methods—Alterations in the adenomatous polyposis coli (APC), p53, and Ki-ras genes were analysed in 24 MSI high (alterations in four to seven of seven loci), nine MSI low (alterations in one to three of seven loci), and 31 MSI negative non-familial carcinomas. The hMSH2 and hMLH1 genes were also analysed in 24 MSI high carcinomas.

Results—Both the frequencies and types of alterations in the APC and p53 genes in MSI high carcinomas were the same as those in MSI low and MSI negative carcinomas; however, they were different from those seen in HNPCC. The frequency of Ki-ras mutation was significantly lower in the MSI high cases (two of 24; 8%) than in the others (15 of 38; 39%). Somatic mutation of hMSH2 or hMLH1 was detected in six of 24 (25%) of the MSI high cases.

Conclusions—These results suggest that APC and p53 alterations occur irrespective of microsatellite instability status in non-familial colorectal carcinomas, and that Ki-ras mutation is not involved in MSI high non-familial colorectal carcinoma. The pathogenesis of these carcinomas may differ from both the usual adenoma–carcinoma sequence and HNPCC carcinogenesis.
Colorectal cancer registration: the central importance of pathology
Authors: Manser M D , Levine D F , Pheby D F H , Pitcher R W
Published: July 2002

Background—Changes in cancer care have increased the importance of cancer registries in monitoring trends and outcomes. Registries are increasingly using computerised systems, such as patient administration and histopathology, as data sources. Omissions by registries can cause interpretation errors, but use of multiple data sources can overcome this.

Methods—Registrations of new colorectal cancers in Cornwall were compared with cases identified from primary sources over one year.

Results—Two hundred and thirty cases were identified locally, 93% in documentary records, 89.6% via histopathology, and 81.3% in the clinical data capture module of the patient administration system. Two hundred and forty four cases were known to the regional registry, but after eliminating wrongly assigned and unconfirmed cases only 201 remained. Twenty nine cases identified locally, particularly cases of advanced disease, were unknown to the registry.

Conclusions—District registers based on histopathology augmented from other sources would provide more accurate and less biased information than existing regionally based methods.
Unusual manifestations of type II cryoglobulinaemia associated with Waldenström's macroglobulinaemia
Authors: Blanco P , Viallard J-F , Rivel J , Leng B , Pellegrin J-L
Published: July 2002

Cryoglobulinaemia in association with Waldenström's macroglobulinaemia is relatively common, ranging from 8% to 18% of cases; however, < 5% have symptoms or complications. We describe a patient with a history of cutaneous, peritoneal, and fallopian tube vasculitis related to type II cryoglobulinaemia associated with Waldenström's macroglobulinaemia. Cytotoxic treatment was initiated (cyclophosphamide, vincristine, and prednisone) and had a good initial response. However, after the third course of chemotherapy, the patient presented with septic shock and died. Even though cryoglobulinaemia is a model of systemic vasculitis, peritoneal and fallopian tube vasculitis associated with type II cryoglobulinemia has not been described previously.
Necropsy diagnosis of myocarditis: a retrospective study using CD45RO immunohistochemistry
Authors: Feeley K M , Harris J , Suvarna S K
Published: July 2002

Aim—To use CD45RO immunohistochemistry to investigate the numbers of T lymphocytes found in sections of myocardium from a routine necropsy series, and to determine the incidence of myocarditis in this series.

Methods—Myocardial sections from 163 routine hospital necropsies were stained with CD45RO and the numbers of positive lymphocytes/mm2were counted. The results were correlated with the H/E opinion and the clinical context of the necropsy.

Results—Most (143) cases showed low numbers (0–3) of CD45RO positive lymphocytes/mm2. Fifteen cases showed 7–13 positive lymphocytes/mm2, comprising a wide variety of clinical conditions, generally with no specific cardiac pathology. Five cases showed 14 or more positive lymphocytes/mm2, comprising one case of active myocarditis, three cases of cardiac transplant rejection, and one post-transplant lymphoproliferative disorder, all conditions in which large numbers of lymphocytes would be expected.

Conclusions—The incidence of myocarditis in our series was 0.6%. In most cases the normal myocardium has a low T lymphocyte count (0–3/mm2). In some cases immunohistochemistry shows more positive cells than would have been expected on light microscopy. Immunohistochemistry is a useful and reliable means of confirming a diagnosis of myocarditis. The results support the conclusion of the 1997 ISFC task force that 14 or more lymphocytes or macrophages/mm2of myocardium in the appropriate clinical context is a reliable threshold for the diagnosis of chronic myocarditis.
Apoptosis in cervical squamous carcinoma: predictive value for survival following radiotherapy
Authors: Paxton J R , Bolger B S , Armour A , Symonds R P , Mao J H , Burnett R A
Published: July 2002

Background—Apoptosis, or programmed cell death, can be induced by radiotherapy. The extent of apoptosis in a tumour before treatment may have important implications for response to radiotherapy and long term survival.

Aim—To examine the extent of apoptosis in tumour tissue from patients with squamous carcinoma of the cervix before radiotherapy, and to correlate this with response to treatment and prognosis.

Methods—The percentage of apoptotic cells was assessed in 146 carcinomas of the cervix from patients scheduled to receive radiotherapy. The CAS 200 static image analysis system was used to count the number of tumour nuclei per high power field, while the numbers of apoptotic cells in the same field were visualised simultaneously on the image analyser and recorded manually.

Results—The median apoptotic level was 0.73%. Patients were divided into two groups around the median. There was no statistically significant difference in outcome between the two groups as determined by long term survival following radiotherapy.

Conclusions—The CAS 200 static image analyser system can be used to assist in the rapid semiautomated assessment of apoptosis in conventionally prepared tissue. The results suggest that the apoptotic state of a tumour before treatment is of no value in predicting response to radiotherapy and subsequent prognosis. Tumour stage, size, and BrdU labelling index, as a measure of proliferation rate, remain the most important prognostic factors in terms of predicting local tumour control.
Expression of a homeobox gene (SIX5) in borderline ovarian tumours
Authors: Winchester C , Robertson S , MacLeod T , Johnson K , Thomas M
Published: July 2002

Aims—To assess the expression of SIX5 (a homeobox gene) mRNA in surface coelomic epithelium, endocervical epithelium, Fallopian tube epithelium, and benign, borderline, and malignant epithelial ovarian tumours.

Methods—10 normal premenopausal ovaries, 10 normal Fallopian tubes, 10 normal cervices, 10 normal postmenopausal ovaries, 10 benign epithelial ovarian tumours, 10 malignant epithelial ovarian tumours, and 40 borderline epithelial ovarian tumours were studied retrospectively. The tissues had been fixed in formalin and embedded in paraffin wax. The tumours had previously been typed into mucinous, serous, or mixed tumours and assigned to the borderline category according to the FIGO/WHO criteria. Expression was assessed by in situ binding of SIX5 specific sense and antisense riboprobes. Hybridisation of the riboprobes was detected using a standard immunohistochemical technique and the results correlated with expression in the normal epithelium of the endocervix, Fallopian tube, surface coelomic epithelium, and ovarian tumours.

Results—Expression of SIX5 mRNA was demonstrated in normal Fallopian tube epithelium and normal endocervical epithelium. SIX5 mRNA was not detected in normal ovarian epithelial tissue at any of the times studied during the menstrual cycle. Expression of SIX5 was not shown in benign epithelial ovarian tumours or in any of the malignant epithelial ovarian tumours. In 31 of 37 borderline epithelial ovarian tumours (84%), SIX5 expression was found in the epithelial cells.

Conclusions—SIX5 expression is present in the normal epithelium throughout most of the female reproductive tract, suggesting it may have a role in maintaining epithelial differentiation in these tissues. SIX5 expression appears to be restricted to borderline epithelial ovarian tumours and may be a marker of epithelial differentiation in these tumours; thus borderline ovarian tumours may not be part of a continuum of disease between benign and malignant epithelial ovarian tumours. Further investigation of expression of SIX5 may clarify the molecular processes that promote differentiation of the ovarian surface epithelium.
Starting clinical trials of xenotransplantation—reflections on the ethics of the early phase
Authors: Welin Stellan
Published: July 2002

What kind of patients may be recruited to early clinical trials of xenotransplantation? This is discussed under the assumption that the risk of viral infection to the public is non-negligible. Furthermore, the conditions imposed by the Helsinki declaration are analysed. The conclusion is that only patients at risk of dying and with no alternative treatment available should be recruited to xenotransplantation trials in the early phase. For some of the less dangerous cell or islet cell xenotransplantation other categories might be recruited. The risk of cell and islet cell xenotransplantation should, however, be weighted against the development of other technologies.

In order to safeguard the public, the opt-out clause in the Helsinki declaration should not be fully applied. Legally binding rules on obligatory monitoring and restrictions should be imposed—before clinical trials start. Journal of Medical Ethics
Are antipsychotic drugs the right treatment for challenging behaviour in learning disability?: The place of a randomised trial
Authors: Ashcroft Richard , Fraser Bill , Kerr Michael , Ahmed Zahir
Published: July 2002

People with learning disability sometimes display challenging behaviour. This can be managed by use of antipsychotic medication or behavioural therapy or both. There is no solid evidence, however, that these therapies are safe and effective. A randomised controlled trial of antipsychotic medication has been proposed to deliver such evidence. However, this presents difficult issues in the ethics of research with learning disabled people. In particular, is a trial the most efficient and fairest way to evaluate practice in this area? This paper reviews the clinical situation, gives the rationale for the trial, and analyses the ethical arguments for and against such a trial.
White coat ceremonies: a second opinion
Authors: Veatch R M
Published: July 2002

A “white coat” ceremony functions as a rite of passage for students entering medical school. This comment provides a second option in response to the earlier, more enthusiastic, discussion of the ceremony by Raanan Gillon. While these ceremonies may serve important sociological functions, they raise three serious problems: whether the professional oath or “affirmation of professional commitment” taken in this setting has any legitimacy, how a sponsor of such a ceremony would know which oath or affirmation to administer, and what the moral implications of this “bonding process” are. I argue that the initiation oath is morally meanignless if students are not aware of its content in advance, that different students ought to commit to different oaths, and that bonding of students to the medical profession necessarily separates them from identification with lay people who will be their patients.
Occupational exposure tocis-1,3-dichloropropene: biological effect monitoring of kidney and liver function
Authors: Verplanke A J W , Bloemen L J , Brouwer E J , Van Sittert N J , Boogaard P J , Herber R F M , De Wolff F A
Published: July 2002

OBJECTIVES

To investigate the possible effects of occupational exposure to the nematocidecis-1,3-dichloropropene (cis-DCP) on function of the kidney and liver in the starch potato growing region in The Netherlands.

METHODS

The study involved 13 commercial application workers exposed tocis-DCP for 117 days, and 22 matched control workers. The inhalatory exposure of the application workers was estimated from biological monitoring data. All workers collected urine and serum samples before, during, and after the fumigation season for monitoring of variables for kidney and liver function. Renal effect variables were alanine aminopeptidase (AAP), N-acetyl-β-D-glucosaminidase (NAG), retinol binding protein (RBP), and albumin (ALB) in urine, and β2-microglobulin (β2M-S) and creatinine in serum (Creat-S). Liver variables were alanine aminotransferase (ALAT), aspartate aminotransferase (ASAT), γ-glutamyltranspeptidase (GGT), alkaline phosphatase (ALP), and total bilirubin (TBIL) in serum and the urinary ratio of 6-β-hydroxycortisol to free cortisol (βOHC/COR).

RESULTS

The geometric mean exposure of the application workers was 2.7 mg/m3(8 hour time weighted average (8 hour TWA)); range 0.1–9.5 mg/m3. No differences were found between the values of the renal effect variables or the liver variables of the exposed group and the control group, except a lower urinary ratio of βOHC/COR in the exposed group. This was not considered to be related to the exposure tocis-DCP. No dose-effect relations were found between the exposure indices and the effect variables.

CONCLUSIONS

The present study does not provide evidence that occupational exposure tocis-DCP in the starch potato growing region causes adverse effects on the kidney or liver at 8 hour TWA exposure concentrations below 9.5 mg/m3(2 ppm).
Iodine deficiency as a cause of brain damage
Authors: Delange F
Published: July 2002

This editorial reviews the impact of iodine deficiency (1) on thyroid function in pregnant women and neonates and (2) on the neurointellectual development of infants and children.

All degrees of iodine deficiency (mild: iodine intake of 50–99 μg/day, moderate: 20–49 μg/day, and severe: <20 μg/day) affect thyroid function of the mother and the neonate as well as the mental development of the child. The damage increases with the degree of the deficiency, with overt endemic cretinism as the severest consequence. Maternal hypothyroxinaemia during early pregnancy is a key factor in the development of the neurological damage in the cretin. Selenium deficiency combined with iodine deficiency partly prevents the neurological damage but precipitates severe hypothyroidism in cretins.

Iodine deficiency results in a global loss of 10–15 IQ points at a population level and constitutes the world’s greatest single cause of preventable brain damage and mental retardation.
Isolated splenic metastasis from carcinoma of the breast
Authors: Iype S , Akbar M A , Krishna G
Published: July 2002

A case of isolated splenic metastasis from carcinoma of the breast in a 54 year old woman, two years after treatment for breast carcinoma, is presented. There was no involvement of other organs like liver, bone, lungs, etc. The patient underwent splenectomy and recovered without any complications. This case is being reported because of the rarity of the lesion.