bluuebunny/crossref_metadata_2025 huggingface dataset:
Functions of the v‐SRC protein tyrosine kinase
Authors: Fincham V. , Frame M. , Haefner B. , Unlu M. , Wyke A. , Wyke J.
Published: October 2002

The peripheral non‐receptor tyrosine kinase oncoprotein, v‐Src, has pleiotropic effects. It is a mitogen for quiescent cells, substituting for both competence and progression factor‐mediated signals but it also induces cellular morphological transformation. We are dissecting the activities of v‐Src by studying mutant proteins, including those with temperature sensitive (ts) effects, in different cellular backgrounds. Activation of a ts v‐Src kinase rapidly increases activity of both the transcription factor, AP‐1, and MAP kinase, an enzyme that enhances AP‐1 activity by both phosphorylation of c‐Jun and increased c‐fos transcription; the relative contribution of these two events depends on the cells in which v‐Src is expressed. Transient early AP‐1 activation requires proper location of v‐Src at the cell periphery and it is essential for mitogenesis. It is not, however, sufficient for entry into S‐phase, there being a second need for v‐Src later in G1. Transformation by v‐Src does not require AP‐1 activation but seems linked to events at the cell periphery, notably phosphorylation of proteins that bind to the v‐Src SH3 domain such as the p85 subunit of PI‐3 kinase.
IL‐1 alpha antiproliferative and differentiative effects on Daudi lymphoma cells: multiparametric analysis.
Authors: Santavenere E. , DI Pietro R. , Centurione M. A. , Trubiani O. , Zamai L. , Rana R.
Published: October 2002

Interleukin Iα (IL‐1) is a potent agent that induces a wide range of biological effects. In this study we analysed its effects on cell cycle progression and differentiation of Daudi Iymphoma cells. The parallel analysis in light microscopy and cytofluorimetry by means of anti‐BrdU monoclonal antibodies showed a reduced rate of proliferation (S phase) with a G1 arrest. These features were confirmed by the lower incorporation of [3H]‐thymidine supporting the decrease in the rate of DNA synthesis. In addition this cytokine was able to induce differentiation after 24 hrs of treatment as assessed by the increased expression of Fc receptors (FcR) and morphological criteria. This multiparametric analysis gives evidence to the sensitivity to this cytokine of this peculiar cell line.
Models for solid‐state transport: messenger RNA movement from nucleus to cytoplasm.
Authors: Agutter Paul S.
Published: October 2002

This paper explores the idea that mRNAs are transported between their transcription and processing sites in the nucleus, and their translation and degradation sites in the cytoplasm, by a ‘solid‐state’ process. The underlying assumption is that negligible quantities of mRNA and of mRNA precursors are in solution in vivo. Therefore, mRNA transport cannot be considered as movement in the aqueous phase of the cell. The main lines of experimental evidence supporting this ‘solid‐state’ concept are summarized and related controversies are outlined. Three possible models for a solid‐state transport mechanism are discussed: a direct transfer model, with receptors organized analogously to the components of a multienzyme complex; a motor‐driven model, analogous to synaptic vesicle transport in axons; and an assembly‐driven model which assumes net movement along a fibril resulting from differential activities at the poles. Qualitative evaluation indicates that each of these models has characteristic advantages and disadvantages. The possibility that other nucleocytoplasmic transport processes might operate by solid‐state mechanisms is briefly discussed.
PCNA Ki‐67 dissociation in childhood acute lymphoblastic leukaemia. An Immunofluorescent Laser Confocal Scanning Microscopical study.
Authors: Ball Lynne M. , Pope Jason , Howard Charles V. , Eccles Paul , van Velzen Dick
Published: October 2002

Cell proliferation rates of diagnostic marrow aspirate cells of 21 children with Acute Lymphoblastic Leukaemia and 16 controls were compared using immunocytochemical labelling of PCNA and Ki‐67 antigen as assessed by Confocal Laser Scanning Microscopy.

The results showed an unexpected, highly significant degree of dissociation between PCNA and Ki‐67 expression in ALL blasts. The PCNA labelling indices of ALL patients were significantly increased (mean 44, range 24‐77) compared with normal reactive marrow cells (mean 13.8, range 4‐26) (p<0.000001, Mann Whitney U two tailed test), suggesting an abnormal commitment to proliferation. Ki‐67 expression was raised to a lesser extent in ALL cells (mean 14.8, range 1.2‐35) when compared to non‐malignant proliferations (mean 6.6, range 1.7‐25) (p < 0.02). PCNA/Ki‐67 LI ratios in ALL (mean 7, range 1.1‐35) were higher than in controls (mean 2.7, range 1.04‐6.5, p<0.09).

As cell proliferation rates actually achieved in the bone marrow do not differ as strongly as suggested by the extreme difference in PCNA labelling, a pathological dissociation of PCNA / Ki‐67 expression exists, suggesting immortalisation.
Urceolaria mitra (von Seib) Epizoic on Polycelis tenuis (IJIMA) an SEM Study.
Authors: Bowen I. D. , Ryder T. A.
Published: October 2002

Dense populations of Urceolaria mitra (Cilophora, Peritrichid) were observed on the surface of the planarian Polycelis tenuis (Platyhelminthes Turbellaria). Although the epizoite was primarily confined to the anterior dorsal surface of the planarian, heavily infested individuals had peritrichs attached to the posterior, lateral and ciliated ventral surfaces. Unique profiles of the skeletal ring (aboral disc) in relation to the host surface showed that some local erosion of planarian epithelium occurs. Outer and inner rows of cilia extended anti‐clockwise around the peristomal disc. The cilia ran for one and one‐eighth turns around the disc and overlapped in the form of a spiral when the protist was extended and feeding. The cilia appeared to beat in metachronal rhythm and exhibited a wavelength and amplitude of approximately 10μm. Regular striations having a periodicity of 1μm were observed in the periostimal membrane. A posterior or basal circlet of locomotor cilia was also observed and freeze fracture revealed an internal arrangement of microvilli, cilia and reticular membranes.
INTEGRIN EXPRESSION AND COLLAGEN TYPE II IMPLICATED IN MAINTENANCE OF CHONDROCYTE SHAPE IN MONOLAYER CULTURE: AN IMMUNOMORPHOLOGICAL STUDY
Authors: SHAKIBAEI M. , De SOUZA P. , MERKER H.‐J.
Published: October 2002

Chondrocytes grown in monolayer culture at low density, with serum added, either dedifferentiate after several days whereby their cell shape changes or they are overgrown by fibroblast‐like cells. The aim of this study was to optimize the cultivation of chondrocytes in monolayer culture and to slow down their transformation or their overgrowth by fibroblast‐like cells. For this purpose freshly isolated chondrocytes of cartilage anlagen from 17‐day‐old mouse embryos were grown on plastic or collagen type II‐coated substrates. With this model: (a) chondrocytes grown on plastic substrates had almost completely changed to fibroblast‐like cells after 5 days in culture. (b) When grown on collagen type II, the chondrocytes maintained their round phenotype for more than 2 weeks in culture. (c) Immunomorphological investigations showed that chondrocytes produce collagen type II and fibronectin and express specific surface receptors (integrins of the β1‐group) on the membrane from day 1 until the end of the culture period when grown on collagen type II. (d) Treatment with β1‐integrin antibodies clearly reduces chondrocyte adhesion on collagen type II by about 70%. Hence, these data indicate that the most probable influence of collagen type II on cellular behaviour depends on the integrins participating in a chondrocyte—collagen type II interaction, and this model represents a pure chondrocyte culture which allows cell growth for an extended period.
OPOSSUM KIDNEY CELLS TAKE UP L‐DOPA THROUGH AN ORGANIC CATION POTENTIAL‐DEPENDENT AND PROTON‐INDEPENDENT TRANSPORTER
Authors: GOMES P. , SERRÃO M.P , VIEIRA‐COELHO M.A , SOARES‐DA‐SILVA P.
Published: October 2002

The present work was aimed at studying the kinetics and nature of the l‐DOPA transporter in opossum kidney (OK) cells. Saturation experiments were performed in OK cells incubated for 6 min with increasing concentrations of l‐DOPA (10 to 2500 μm); non‐linear analysis of the saturation curve revealed for l‐DOPA aKmof 129 μm (114, 145) and aVmaxof 30.0±0.4 nmol mg protein−16 min−1The uptake of l‐DOPA (250 μm) was inhibited in a concentration‐dependent manner by cyanine 863, an organic cation inhibitor, with aKivalue of 638 (430, 947) μmthe organic anion inhibitor 4,4′‐diisothiocyanostilbene‐2,2′‐disulphonic acid (DIDS), was devoid of effect upon the uptake of l‐DOPA. The uptake of l‐DOPA (250 μm) was significantly (P<0.02) decreased (25% reduction) when cells were incubated in the presence of 137 mm K+plus 5 mm Na+when compared with the control condition (137 mm Na+plus 5 mm K+); substitution of NaCl by choline chloride (137 mm) did not affect l‐DOPA uptake. Similarly, inwardly or outwardly directed proton gradients of 0.5 pH units (7.9, 7.4, 6.9, 6.4 and 5.9) were found not to change l‐DOPA uptake. In conclusion, the l‐DOPA uptake system in OK cells has the characteristics of an organic cation potential‐dependent and proton‐independent transporter.
THE BIOSTIMULATORY EFFECT OF RED LASER IRRADIATION ON PIG BLOOD PLATELET FUNCTION
Authors: OLBAN MONIKA , WACHOWICZ BARBARA , KOTER MARIA , BRYSZEWSKA MARIA
Published: October 2002

The molecular mechanisms of laser‐induced changes in the cell structure and function are not well known. The authors examined the effects of low‐power laser irradiation on unnucleated pig blood platelets. The obtained results showed that laser irradiation (1–5J) caused in blood platelets lipid peroxidation (measured as thiobarbituric acid reactive substances) and super‐oxide anion generation, concomitant with the release of adenine nucleotides and proteins from platelets. The maximum platelet response to laser irradiation was observed when doses of 1.8–2J were used. Our results indicate that red laser irradiation induces: (1) platelet secretory process and the release of substances stored in the specific granules (adenine nucleotides, proteins); and (2) lipid peroxidation partly due to stimulation of endogenous arachidonate and production of its metabolites reacting with thiobarbituric acid.
DISCORDANCE BETWEEN THE EFFECT OF MODULATORS OF CALCIUM ON STAUROSPORINE‐INDUCED APOPTOSIS AND STAUROSPORINE‐INDUCED ACTIN DEGRADATION
Authors: Rabkin Simon W. , Kong Jennifer Y.
Published: October 2002

Staurosporine produced DNA fragmentation characteristic of apoptosis and a dramatic alteration of cell structure that include alterations of cytoskeletal actin and cytoplasmic condensation with vacuolization. These changes were not induced by chelerythrine, a more specific PKC inhibitor than staurosporine. The calcium chelator, BAPTA, significantly reduced staurosporine‐induced DNA fragmentation but did not affect staurosporine‐induced changes in cytoskeletal actin. These data suggest that DNA fragmentation and actin degradation in apoptosis, induced by staurosporine, are under different regulatory control by calcium.
SOLUBILITY PARTITIONING OF C/EBPβ ON THE RAT HEPATOCYTE NUCLEAR MATRIX BY HYDROPHOBIC INTERACTIONS
Authors: Uskoković Aleksandra , Vidaković Melita , Dinić Svetlana , Ivanović‐Maticć Svetlana , Martinović Vesna , Poznanović Goran
Published: October 2002

The greatest part of nuclear C/EBPβ (a major 35kD protein, 30 and 38kD isoforms) was observed to partition with the nuclear matrix. Cross‐linking experiments with formaldehyde suggested that the association reflected the in situ juxtapositioning of C/EBPβ to nuclear matrix proteins in isolated nuclei. The association of C/EBPβ with the nuclear matrix resisted RNase and DNase treatment and extraction with protein sulfhydryl reducing agents combined with high ionic strength salt. C/EBPβ displayed a proclivity to extensively reassemble with the filament‐forming nuclear matrix proteins after a cycle of solubilization with urea, followed by its removal by dialysis. These findings suggest that the C/EBPβ moieties were anchored to the nuclear matrix through hydrophobic protein‐protein interactions with the lamins. Subsequent separation of nuclear matrix‐associated C/EBPβ into insoluble, reassembling, and soluble nuclear matrix protein (SNMP) fractions after a cycle of solubilization/reassembly pointed to the sub‐partitioning of C/EBPβ on the nuclear matrix. DNA affinity chromatography using the rat haptoglobin gene cis ‐element and SNMP revealed the binding of p35 during basal transcription, and p35 and p30 during elevated haptoglobin gene transcription in the course of the acute‐phase (AP) response. It was concluded that the appearance of cis ‐element‐binding p30 in the SNMP fraction resulted from its increased solubility (decreased hydrophobicity) and inability to reassociate with the lamins during urea removal. The observed solubility partitioning of C/EBPβ on the nuclear matrix framework could represent a level of control of the general availability of regulatory proteins for establishing interactions with DNA.
A Pre-Illinoian Pleistocene Fossil Assemblage from Near Connersville, Southeastern Indiana
Authors: Miller Barry B. , Palmer Donald F. , McCoy William D. , Smith Alison J. , Colburn Mona L.
Published: October 2002

A fossil assemblage containing molluscs, ostracodes, and fish has been recovered from lacustrine sediments from near Connersville, southeastern Indiana. The reversed remanent magnetic signature of the sediments and the extent of isoleucine epimerization in molluscan shell protein indicate a pre-Illinoian age for the fossils. The fauna includes four taxa of fish,Coregonussp., cf.Prosopiumsp., cf.Thymallus arcticus,andCatostomussp.; four taxa of ostracodes,Cytherissa lacustris, Candona caudata, Cyclocypris ampla,andCandonasp.; and 28 taxa of molluscs. Elements of the aquatic molluscs, fish, and ostracodes suggest a cool-water lake (8° to 16°C). The terrestrial molluscs include boreal species that now reach the southern limits of their range in the Great Lakes region near the north shore of Lake Superior and imply average summer temperatures of about 15°C near the lake margins. The lake may have been formed when West Lebanon ice advanced into the Anderson-New Castle Buried Valley system which drained northwest as a tributary of the Lafayette Bedrock Valley System.
The Faunal Remains from Evron Quarry in Relation to Other Lower Paleolithic Hominid Sites in the Southern Levant
Authors: Tchernov Eitan , Horwitz Liora Kolska , Ronen Avraham , Lister Adrian
Published: October 2002

The mammalian assemblage and archaeological finds from the Lower Palaeolithic hominid site of Evron Quarry, situated on the northern coastal plain of Israel, are described and discussed. In their lithic and faunal composition, the sites of Latamne (QfIII) (Latamne Formation, Orontes, Syria) and Sitt Markho (Nahr elKebir, Syria) resemble Evron and are probably contemporaneous. It is suggested here, based on their lithic and faunal composition, that these sites may be chronologically closer to the site of Ubeidiya ('Ubeidiya Formation, Jordan Valley, Israel; 1.4 myr) than to the sites of Gesher Benot Ya'akov (dated as <800,000 yr B.P.), which differs in both aspects from Evron. The mammalian faunule from Evron comprises a biogeographical mixture, a result of biotic exchanges with Africa, the Oriental region, and the Palaearctic. This exchange may have been associated with a post-'Ubeidiya hominid dispersal, either from Africa or south Asia via the Levantine "corridor."
El Niño Variability in the Coastal Desert of Southern Peru during the Mid-Holocene
Authors: Fontugne Michel , Usselmann Pierre , Lavallée Danièle , Julien Michèle , Hatté Christine
Published: October 2002

Fourteen organic-rich sedimentary layers in the deposits at Quebrada de los Burros, in coastal southern Peru (Tacna department), lie between two debris-flow units, interpreted to result from El Niño events, at 8980 cal yr B.P. and after 3380 cal yr B.P., respectively. The accumulation of the fine-grained and low-energy sediments of this deposit during the mid-Holocene is incompatible with the occurrence of El Niño events in this region, as these would produce catastrophic flood deposits. The occurrence of organic-rich sediments and evidence of an enhancement of upwelling strength at this time imply the existence of a permanent water supply resulting from an increased condensation of fog at mid-altitudes. These results suggest a lower intensity and perhaps, a lower frequency of occurrence of the El Niño phenomenon during the mid-Holocene. It is precisely during this period that the most important human settlements are found at this site, probably indicating the presence of reliable supply of fresh water. The chronologies for wetlands in the central south altiplano are out of phase with those indicating increased soil moisture episodes on the coast, implying a long-term difference in climate between these two regions.
Overtaking in Asynchronous Periodic Systems
Authors: Pitt D. H. , Shields M. W.
Published: October 2002

In this paper, we investigate the structure of the asynchronous behaviour of systems of cyclical, deterministic sequential processes. Specifically, we find conditions which, under certain finiteness assumptions, characterise periodic behaviours and pseudo-periodic behaviours, where a behaviour is periodic if it goes through a sequence of periods, i.e. of behaviours in which each active process executes one complete cycle, and a behaviour is pseudo-periodic, if it can be viewed as being composed of periods, possibly not happening in sequence. Thus, every periodic behaviour is pseudo-periodic. We identify a property, no overtaking, which a pseudo-periodic behaviour must have in order to be periodic.
A Structured Way to Use Channels for Communication in X-Machine Systems
Authors: Cowling Anthony J. , Georgescu Horia , Vertan Cristina
Published: October 2002

This paper presents a new model for passing messages in communicating stream X-machine systems (CSXMS). The components are stream X-machines with ε-transitions, acting simultaneously. The states are partitioned into processing and communicating states. Passing messages between the X-machines involves only communicating states. A communication matrix is used as a common memory. It is shown that a structured way of using channels, namely via
select
constructs with guarded alternatives and
terminate
clause, may be implemented. An automatic scheme for writing concurrent programs in an Ada-like style, starting from a CSXMS, is proposed.
Relating Z and First-Order Logic
Authors: Martin Andrew P.
Published: October 2002

Despite being widely regarded as a gloss on first-order logic and set theory, Z has not been found to be very supportive of proof. This paper attempts to distinguish between the different philosophies of proof in Z. It discusses some of the issues which must be addressed in creating a proof technology for Z, namely schemas, undefinedness, and what kind of logic to use.
Inhibitory effect of epigallocatechin‐3‐gallate on growth and invasion in human biliary tract Carcinoma cells
Authors: Takada Moriatsu , Ku Yonson , Habara Kazuto , Ajiki Tetsuo , Suzuki Yasuyuki , Kuroda Yoshikazu
Published: October 2002

Based on recent evidence that tea consumption contributes to a decreased incidence of human carcinomas, a number of investigators have focused on the mechanisms of cancer prevention by tea extracts, especially green tea polyphenols. Epigallocatechin‐3‐galIate (EGCG) is a representative polyphenol that inhibits the activity of the cyclin‐dependent kinases of cdk2 and cdk4. This suggests that EGCG may exert its growth‐inhibitory effects through modulation of G1 regulatory proteins such as cdk2 and cdk4. The human biliary tract carcinoma cells (TGBC‐2, SK‐ChA‐1, and NOZC‐1) were treated with different doses of EGCG (0, 25, 50, 100, and 200 µM) for 48 hours in cell medium. Cell proliferation was analyzed by WST‐1 colorimetric assay. For the cell‐invasion analysis, the cells were incubated with 100 µM of EGCG for 2 hours. The cells were then added into a Matrigel‐coated Cell Insert. After incubation at 37°C for 24 hours, the cells visible through the Matrigel were counted under the microscope. All human biliary tract cancer cells studied showed a significant suppression of cell growth by EGCG treatment in a dose‐dependent manner (27.2%, 16.0%, and 10.1%, in TGBC‐2, SK‐ChA‐1, and NOZC‐1, respectively, at the dose of 200 µM). EpigaIlocatechin‐3‐gallate treatment also produced a significant suppression of invasive ability of the carcinoma cells (12.6%, 11.2%, 7.9%, in TGBC‐2, SK‐ChA‐1, and NOZC‐1, respectively, at a dose of 100 µM). These data indicated that EGCG might be a potent biological inhibitor of human biliary tract cancers, reducing their proliferative and invasive activities.
Utility of WT1 as a Reliable Tool for the Detection of Minimal Residual Disease in Children with Leukemia
Authors: Kletzel Morris , Olzewski Marie , Huang Wei , Chou Pauline M.
Published: October 2002

WT1 encodes a transcription factor involved in the pathogenesis of Wilms' tumor. A high level of expression has been reported in blasts from patients with various hematological malignancies. The study was performed to evaluate the utility of monitoring WT1 expression in children with leukemia at diagnosis, during therapy, and following bone marrow transplant. We tested a total of 204 samples prospectively. These included samples from patients with the following diagnoses: acute lymphoblastic leukemia (ALL) at diagnosis ( n = 45), at relapse ( n = 14), and in remission ( n = 45); acute non-lymphoblastic leukemia (ANLL) at diagnosis ( n = 14), at relapse ( n = 5), and in remission ( n = 12); and chronic myelogenous leukemia (CML) in blast crisis ( n = 1) and in chronic phase ( n = 1). A total of 33 of these patients were transplanted: 19 ALL, 12 ANLL, and 2 CML. In addition, samples from 5 patients with aplastic anemia and 28 controls were obtained from peripheral blood ( n = 17), cord blood ( n = 3), and bone marrow ( n = 8). Primer pairs were designed to locate specific nucleotide sequences for mRNA of WT1. RT-PCR was performed in all samples and compared with K562 cells from ATCC (defined as 1.0) as positive control. A positive test was arbitrarily defined as WT1/K562 > 0.5. Samples at diagnosis and relapse, including 56 out of 59 ALL (95%), 26 ANLL (100%), and 1 CML in blast crisis, demonstrated high levels of WT1 expression. In contrast, only 5 of 90 samples obtained in remission or post-transplant showed high levels of WT1 expression ( P < 0.0001; 95% CI = 0.66–0.94). The five patients with high WT1 expression during follow-up relapsed within 2 to 6 months. In conclusion, we have found that WT1 is consistently elevated in children with leukemia. Significant differences in the level of WT1 expression were noted between these patients during diagnosis and at relapse, and those during remission. More importantly, following bone marrow transplant, a significant high level of WT1 expression preceded clinical relapse by 2 to 6 months. Therefore, WT1 is a reliable marker for monitoring minimal residual disease during therapy as well as in the post-transplant period.
Recirculation within a fluid sphere at moderate
Reynolds numbers
Authors: BARRY D. A. , PARLANGE J.-Y.
Published: September 2002

Motion of a single fluid sphere is described by two theories, each characterized by
different levels of Hill's vortex circulation within the sphere. An existing experimental
data set giving measurements of vertical velocity along the major axis of the sphere
is re-examined. Contrary to published discussions of that experiment, we find that
the theory of Parlange agrees better with the laboratory data than that of Harper &
Moore. This agreement supports the key difference between the two theories, i.e. that
the fluid within the sphere is unlikely to have a singular (infinite) velocity as it moves
upwards towards the stagnation region at the top of the sphere.
Navier–Stokes solutions of unsteady separation
induced by a vortex
Authors: OBABKO A. V. , CASSEL K. W.
Published: September 2002

Numerical solutions of the unsteady Navier–Stokes equations are considered for the
flow induced by a thick-core vortex convecting along a surface in a two-dimensional
incompressible flow. The presence of the vortex induces an adverse streamwise pressure
gradient along the surface that leads to the formation of a secondary recirculation
region followed by a narrow eruption of near-wall fluid in solutions of the unsteady
boundary-layer equations. The locally thickening boundary layer in the vicinity of
the eruption provokes an interaction between the viscous boundary layer and the
outer inviscid flow. Numerical solutions of the Navier–Stokes equations show that
the interaction occurs on two distinct streamwise length scales depending upon which
of three Reynolds-number regimes is being considered. At high Reynolds numbers,
the spike leads to a small-scale interaction; at moderate Reynolds numbers, the flow
experiences a large-scale interaction followed by the small-scale interaction due to
the spike; at low Reynolds numbers, large-scale interaction occurs, but there is no
spike or subsequent small-scale interaction. The large-scale interaction is found to
play an essential role in determining the overall evolution of unsteady separation
in the moderate-Reynolds-number regime; it accelerates the spike formation process
and leads to formation of secondary recirculation regions, splitting of the primary
recirculation region into multiple corotating eddies and ejections of near-wall vorticity.
These eddies later merge prior to being lifted away from the surface and causing
detachment of the thick-core vortex.
An outbreak of hepatitis A among homosexuals linked to a family outbreak
Authors: STENE-JOHANSEN K. , JENUM P. A. , HOEL T. , BLYSTAD H. , SUNDE H. , SKAUG K.
Published: September 2002

Several outbreaks of hepatitis A occurred in Norway in 1995–8. Molecular epidemiology was used to follow the spread of hepatitis A virus in the population. Distinct strains of hepatitis A virus (HAV) were detected by reverse transcriptase–polymerase chain reaction (RT–PCR) and subsequent sequencing in serum from patients in different communities at risk of infection. Two HAV strains were detected in an outbreak among 26 men having sexual contact with other men. One of these strains was also detected in a geographically limited family outbreak. The family outbreak was first believed to be acquired abroad. The sequence information linked the two outbreaks, and epidemiological and serological analyses revealed the transmission route. This study demonstrates the importance of molecular epidemiology in outbreak investigation, surveillance and monitoring of hepatitis A in the population.
A clarification of transmission terms in host-microparasite models: numbers, densities and areas
Authors: BEGON M. , BENNETT M. , BOWERS R. G. , FRENCH N. P. , HAZEL S. M. , TURNER J.
Published: September 2002

Transmission is the driving force in the dynamics of any infectious disease. A crucial element in understanding disease dynamics, therefore, is the ‘transmission term’ describing the rate at which susceptible hosts are ‘converted’ into infected hosts by their contact with infectious material. Recently, the conventional form of this term has been increasingly questioned, and new terminologies and conventions have been proposed. Here, therefore, we review the derivation of transmission terms, explain the basis of confusion, and provide clarification. The root of the problem has been a failure to include explicit consideration of the area occupied by a host population, alongside both the number of infectious hosts and their density within the population. We argue that the terms ‘density-dependent transmission’ and ‘frequency-dependent transmission’ remain valid and useful (though a ‘fuller’ transmission term for the former is identified), but that the terms ‘mass action’, ‘true mass action’ and ‘pseudo mass action’ are all unhelpful and should be dropped. Also, contrary to what has often been assumed, the distinction between homogeneous and heterogeneous mixing in a host population is orthogonal to the distinction between density- and frequency-dependent transmission modes.
Inter-test reliability of the anti-RESA indices based on ELISA tests using eluates from whole blood spots dried on filter paper
Authors: DUARTE E. C. , GYORKOS T. W. , PANG L. , ÁVILA S. , FONTES C. J. F.
Published: September 2002

The ring-infected erythrocyte surface antigen (RESA), is one of the falciparum malaria vaccine candidates rarely studied in Brazil. Fieldwork logistics to conduct serology studies is simplified when eluates from whole blood dried on filter paper can be used. Therefore, this study aimed to assess the inter-test reliability for the anti-RESA ELISA-based indices using eluates from filter paper and from serum samples. The study population consisted of 210 individuals (Brazil) from whom matched samples were collected. Anti-RESA ELISA-based index means (±S.D.) were 15.29% (±28.13%) for filter paper and 11.79% (±23.67%) for serum samples. The intra-class correlation coefficient was estimated to be 82.38%, indicating high test reliability. However, there was a significant tendency for filter paper test results to have higher values than serum sample test results (P<0.001). Explanations for this finding may be the presence of haemoglobin in the eluates from filter paper, which may interfere with ELISA testing.
Transmission of Actinobacillus pleuropneumoniae in pigs is characterized by variation in infectivity
Authors: VELTHUIS A. G. J. , DE JONG M. C. M. , STOCKHOFE N. , VERMEULEN T. M. M. , KAMP E. M.
Published: September 2002

Ten transmission trials with Actinobacillus pleuropneumoniae were carried out. The observed transmission was highly variable, which was surprising since the design of the trials was very similar. We investigated whether the variable transmission could be explained by variation in infectivity of A. pleuropneumoniae infected pigs. We looked for measurable characteristics, which could be indicative for infectious pigs or for the level of infectivity. The characteristic that appeared to be most indicative for a pig being infectious was an A. pleuropneumoniae positive tonsil at necropsy. The characteristic that was correlated to the level of infectivity was the number of A. pleuropneumoniae colonies isolated from the nasal swab, i.e. the probability for an infectious pig to infect a susceptible pig was tenfold higher on days where at least ten colonies were isolated. In this study it is shown that it is possible to measure the bacterial transmission of A. pleuropneumoniae under controlled circumstances if variation in infectivity is taken into account.
Abnormalities of somatosensory perception in patients with painful osteoarthritis normalize following successful treatment
Authors: Kosek Eva , Ordeberg Gunnar
Published: September 2002

To investigate the effect of chronic nociceptive pain on somatosensory perception, quantitative sensibility testing was performed in the most painful area and the homologous contralateral side in 14 patients with painful osteoarthritis of the hip. Twelve patients were reassessed in a painfree state 6–14 months following surgery. Von Frey filaments were used to test low‐threshold mechanoreceptive function. Pressure pain sensitivity was assessed with a pressure algometer and thermal sensitivity with a Thermotest®. Sex‐ and age‐matched controls were examined in the corresponding areas at similar time intervals. There was no statistically significant difference between groups in the sensitivity to light touch and innocuous cold in either session. Compared to controls, patients had increased sensitivity to pressure pain in the most painful area (p< 0.002), bilaterally increased sensitivity to innocuous warmth (p< 0.03), cold pain (p< 0.05) and a tendency toward bilaterally increased sensitivity to heat pain (p= 0.054) before surgery. In the painful area, patients’ sensitivity to pressure pain decreased (p< 0.04) and, remaining within normal limits, sensitivity to light touch increased (p< 0.006) compared to values prior to surgery. No statistically significant differences between the groups were seen following surgery, indicating that the sensibility changes had been maintained by chronic nociceptive pain.
Intrathecally administered endotoxin or cytokines produce allodynia, hyperalgesia and changes in spinal cord neuronal responses to nociceptive stimuli in the rat
Authors: Reeve Alison J. , Patel Sadhana , Fox Alyson , Walker Katherine , Urban Laszlo
Published: September 2002

Inflammatory processes occurring within the central nervous system (CNS) can produce ‘illness induced behaviours’ which include fever, sleep and the development of allodynia and hyperalgesia. Here we demonstrate the effects of the pro‐inflammatory mediators, bacterial endotoxin, and rat recombinant interleukin 1 β (rrIL‐1β) or tumour necrosis factor‐ α (rrTNF α) on the integration of somatosensory information at the single neuronal level, via recordings from wide‐dynamic range neurones in the dorsal horn of the spinal cord in anaesthetized rats. Intrathecal administration of E. coli lipopolysaccharide (LPS, 10 and 100 μ g, i.t.) enhanced the activity of dorsal horn neurones, including facilitation of neuronal post‐discharge. Intrathecal administration of IL‐1β (5–5000 pg) or TNF‐ α (5–5000 pg) enhanced dorsal horn neuronal responses, including the acute responses to C‐fibre stimulation, wind‐up and post‐discharge, however, the effects of IL‐1 β were more robust than those of TNF α. Intrathecal administration of IL‐1 β (1–1000 pg) also leads to the development of mechanical allodynia and hyperalgesia. On the other hand intrathecal application of TNF α did not produce changes in sensitivity to mechanical stimuli. Changes in the activity of spinal wide‐dynamic range neurones induced by local inflammation may provide a pathomechanism for the clinical pathology of central pain syndrome, which can accompany CNS disease or acute CNS injury.
Reciprocal connections between the medullary dorsal reticular nucleus and the spinal dorsal horn in the rat
Authors: Almeida Armando , Tavares Isaura , Lima Deolinda
Published: September 2002

The synaptic architecture of spinal afferents of the dorsal portion (DRtd) of the medullary dorsal reticular nucleus (DRt) is studied. After iontophoretic injections of cholera toxin subunit B (CTb) into the superficial (laminae I–II), deep (laminae IV–V) or entire (laminae I–V) dorso‐ventral extent of the spinal dorsal horn at the cervico‐thoracic or lumbo‐sacral levels, axonal boutons of two distinct types were labelled in the DRtd. Type A boutons (82% after cervico‐thoracic injections and 92% after lumbo‐sacral injections) were roundish, small and presented few mitochondria and small, round synaptic vesicles. Type B boutons (18% after cervico‐thoracic injections and 8% after lumbo‐sacral injections) were elongated, two to three times larger, and exhibited numerous mitochondria and larger round vesicles. Both types of bouton established asymmetrical synaptic contacts with small dendritic profiles and, less frequently, with dendritic trunks and perikarya. Retrograde labelling occurred in the postsynaptic profile of 15–18% type A boutons labelled from any injection site.

Taken together with previous data on DRt‐spinal synaptic contacts at the superficial dorsal horn, the present results point to the occurrence of a reciprocal excitatory loop connecting the dorsal DRt and lamina I, which may be at the basis of the DRt‐mediated pain‐facilitating effects described recently.
Lack of stereoselectivity for the antiallodynic effect of mexiletine in spinally injured rats
Authors: Wu Wei‐Ping , Nordmark Jan , Wiesenfeld‐Hallin Zsuzsanna , Xu Xiao‐Jun
Published: September 2002

Systemically administered mexiletine, an antiarrhythmic, has been shown to also possess analgesic properties in some conditions of neuropathic pain. It has been suggested that the analgesic effect of mexiletine may be derived from the action of one of its optical isomers, (+)(S)‐mexiletine. In the present study, we have compared the effects of systemic (−)‐(R)‐ and (+)‐(S)‐mexiletine, on chronic mechanical allodynia‐like behaviour in spinally injured rats, a model of central neuropathic pain in which racemic mexiletine has been shown to be active. I.p. racemic mexiletine as well as (−)‐(R)‐ and (+)(S)‐mexiletine at 25 mg/kg all produced significant, but brief, alleviation of mechanical allodynia in a similar fashion as assessed with von‐Frey hair elicited vocalization in the spinally injured rats. A slight increase in motor impairment was observed in all three groups which reached statistical significance for the racemic mexiletine and (+)‐(S)‐mexiletine. Our results suggest that both isomers of mexiletine contribute to the antiallodynic effect in this model of central pain.
Inefficacy of high‐dose transdermal fentanyl in a patient with neuropathic pain a case report
Authors: Bleeker Chris P. , Bremer Robbert C. , Dongelmans Dave A. , van Dongen Robert T.M. , Crul Ben J.P.
Published: September 2002

Pain partially responsive to opioids can lead to rapid escalating dosages due to tolerance development. In this report the case of a 58‐year‐old female with neuropathic pain using increasing transdermal (TTS) fentanyl dosages to a maximum dose of 3400 μg/h resulting in fentanyl plasma levels of 173 ng/ml is described. For pain relief an epidural infusion at the level T1–2 with bupivacaine was started. Immediate pain relief was accompanied by short lasting respiratory depression and drowsiness.
Efficacy of spinal cord stimulation: 10 years of experience in a pain centre in Belgium
Authors: Van Buyten Jean‐Pierre , Van Zundert Jan , Vueghs Peter , Vanduffel Luc
Published: September 2002

Spinal cord stimulation is a minimally invasive mode of treatment in the management of certain forms of chronic pain that do not respond to conventional pain therapy. Several authors have reported encouraging findings with this technique. Over a 10‐year period in a single centre, 254 patients were subjected to a trial period of spinal cord stimulation with an externalized pulse generator. Two hundred and seventeen of the patients showed satisfactory results justifying permanent implantation of a spinal cord stimulation system. In 1998, an independent physician invited 153 patients (155 pain cases), who still had the system in place and who could be contacted, for an interview. The aim of this study was to evaluate the efficacy of an implanted spinal cord stimulation system in terms of pain relief and quality of life and to assess the accuracy of the patient selection criteria. The results of this study demonstrate a high success rate as evaluated by the patients' own assessments—68% of the patients rated the result of the treatment as excellent to good after an average follow‐up of almost 4 years. The resumption of work by 31% of patients who had been working before the onset of pain supports these positive findings.
Peripheral neuropathic pain—a multidimensional burden for patients
Authors: Meyer‐Rosberg Karin , Kvarnström Ann , Kinnman Erik , Gordh Torsten , Nordfors Lars‐Olof , Kristofferson Ann
Published: September 2002

The present study was undertaken to assess the health‐related quality of life (HRQoL) and burden of illness due to pain and its treatment for patients with peripheral neuropathic pain (PNP). It is the first step in finding reliable instruments/targets to evaluate treatment outcome in this patient population. Study population consisted of 126 patients suffering from neuropathic pain due to a peripheral nerve or root lesion, recruited from two multidisciplinary pain clinics. HRQoL was examined using Short Form 36 (SF‐36) Health Survey and Nottingham Health Profile (NHP). Pain intensity in four categories (at rest and evoked by movement, touch and cold) was rated on a visual analogue scale (VAS). Degree of discomfort from pain and 25 symptoms related to pain and side‐effects was also assessed. Reduction in workload due to pain was recorded, as was the pain relief from previous and current treatments and the reasons for discontinuing previous treatments.

All dimensions in SF‐36 and NHP were significantly impaired. SF‐36 was a valid instrument for describing the impact of pain on the HRQoL of patients with PNP. NHP had a lower reliability but has other advantages that might be of importance. Many patients experienced poor pain relief from ongoing pain treatments. Most previous treatments were discontinued owing to lack of efficacy and/or severe side‐effects. Many patients experienced a high intensity of at least one type of pain; median VAS for the highest pain intensity score of each patient (any type of pain) was 74/100. Besides pain, patients were most bothered by difficulty in sleeping, lack of energy, drowsiness, difficulty in concentrating and dry mouth. Employment status was reduced owing to pain in 52% of the patients.

The intense pain, other troublesome symptoms, limited efficacy and tolerability of available treatments, together with the impaired health and reduced work status, amount to a substantial burden for patients with PNP.
The truth about pain management: the difference between a pain patient and an addicted patient
Authors: Heit Howard A.
Published: September 2002

Pain is undertreated in all parts of the world. Multiple barriers exist that prevent valid treatment of the pain patient. This paper will provide definitions of pain, addiction, physical dependence, tolerance, and pseudoaddiction that health professionals need to understand in order to treat pain. It will address how to differentiate between a pain patient and an addict when evaluating the patient for treatment. The physiological benefits of using long‐ versus short‐acting opioids will be presented. With proper education of the medical community, patients should receive humane and compassionate treatment of their chronic pain syndromes.
Direct and indirect costs of managing patients with musculoskeletal pain—challenge for health care
Authors: Mäntyselkä Pekka T. , Kumpusalo Esko A. , Ahonen Riitta S. , Takala Jorma K.
Published: September 2002

Musculoskeletal pain is an outstanding symptom among the patients of primary health care. However, there are few studies of management and costs of musculoskeletal pain at primary health care level. The aim of this study was to describe the diagnostic investigations, management, referral rate and sick leaves related to visits prompted by musculoskeletal pain as well as to assess their costs. A total of 28 general practitioners (GPs) at 25 randomly selected health centres throughout Finland collected the data for this 4 week study, which covered 1 week from each of the four seasons. All visits, except those occurring after hours, were recorded. Altogether 1123 patients visited GPs because of musculoskeletal pain. Laboratory tests were ordered for 12% and imaging investigations for 24%. A total of 16% of the patients suffering from musculoskeletal pain received a prescription for physiotherapy, and analgesics were prescribed to 61% of them. Physicians referred 7% of the pain patients to specialist care. One out of every four patients was prescribed sick leave. The mean cost of the investigations, therapy, referrals, and sick leaves was as high as 530 EUR per visit, with absenteeism from work constituting two‐fifths of the total costs. Musculoskeletal pain is not just a frequent complaint but also has extensive economic consequences for society. Investigations and therapy at the primary health care level play a minor role in the costs as compared with specialist care and sick leaves. © 2002 European Federation of Chapters of the International Association for the Study of Pain
Ectopic Lingual Thyroid Tissue in a Cat
Authors: Patnaik A K , Peterson M E , Hidgon A
Published: September 2002

Ectopic thyroid tissue was identified at the base of the tongue in a 9-year-old, euthyroid, domestic shorthair cat. The lingual submucosa and the muscles were replaced by thyroid tissue, which consisted of various-sized follicles each lined by a row of cuboidal epithelium. Many follicles contained eosinophilic, periodic acid Schiff-positive, colloid material. Imunohistochemically, the epithelial cells stained positive for AE1/AE3 and thyroglobulin. No calcitonin positive cells or parathyroid tissue was seen. The cat has been followed for 1018 days after surgery, is clinically well and remains euthyroid.
Review of Feline Pancreatitis Part Two: Clinical Signs, Diagnosis and Treatment
Authors: Mansfield CS , Jones BR
Published: September 2002

In the past decade pancreatitis has become recognised as a significant disease in the cat. Chronic, mild pancreatitis is often associated with more commonly diagnosed diseases such as inflammatory bowel disease or cholangitis/cholangiohepatitis. Furthermore, acute pancreatitis with similar complications to those seen in dogs is now diagnosed more frequently in cats. Unfortunately, the clinical signs and clinicopathological findings in cats with pancreatitis are often non-specific and vague. The lack of specific signs often results in a diagnosis being made only when the veterinary surgeon has a strong index of suspicion for pancreatitis and vigorously pursues that diagnosis. Pancreatitis is an important disease in cats, has been implicated as a potential cause of diabetes mellitus, and when present complicates the treatment of diabetes and other intra-abdominal diseases in cats.
Do homeopathic medicines provoke adverse effects? A systematic review
Authors: Dantas F , Rampes H
Published: September 2002

Objective: To evaluate the safety of homeopathic medicines by critically appraising reports of adverse effects published in English from 1970 to 1995.

Method: Systematic review on information regarding adverse effects of homeopathic medicines identified using electronic databases, hand searching, searching reference lists, reviewing the bibliography of trials, and other relevant articles, contacting homeopathic pharmaceutical companies and drug regulatory agencies in UK and USA, and by communicating with experts in homeopathy.

Results: The mean incidence of adverse effects of homeopathic medicines was greater than placebo in controlled clinical trials (9.4/6.1) but effects were minor, transient and comparable. There was a large incidence of pathogenetic effects in healthy volunteers taking homeopathic medicines but the methodological quality of these studies was generally low. Anecdotal reports of adverse effects in homeopathic publications were not well documented and mainly reported aggravation of current symptoms. Case reports in conventional medical journals pointed more to adverse effects of mislabelled ‘homeopathic products’ than to true homeopathic medicines.

Conclusions: Homeopathic medicines in high dilutions, prescribed by trained professionals, are probably safe and unlikely to provoke severe adverse reactions. It is difficult to draw definite conclusions due to the low methodological quality of reports claiming possible adverse effects of homeopathic medicines.