bluuebunny/crossref_metadata_2025 huggingface dataset:
A review of minor injuries telemedicine
Authors: Benger Jonathan
Published: October 2002

Video support in the management of minor injuries was pioneered in the mid-1970s in the USA, but remained little more than a technical curiosity pending the development of acceptable equipment some 20 years later. Minor injuries telemedicine has developed very successfully over the last few years in the UK, the first reported UK minor injuries telemedicine link being set up in 1994. Peripheral services are generally staffed by emergency nurse practitioners, who can use a telemedicine link when required to obtain realtime advice from a doctor at a main hospital accident and emergency department. There is now a considerable body of experience to show that the technique is safe and effective, and also some limited data about its economic benefits. The majority of minor injuries teleconsultations involve transmission of radiographs and most minor injuries teleradiology is undertaken on the understanding that a definitive radiologist's report will be issued in due course. Studies show that satisfactory interpretation of plain radiographs is possible using a low-cost/low-resolution telemedicine link. This is supported by other studies which have shown that even ateleradiology system at reduced cost and technical specifications can yield adequate images. It seems likely that teleconsultation will become an essential component in the provision of accident and emergency services.
Colour perception in telemedicine
Authors: Tachakra Sapal
Published: October 2002

A doctor's experience of examining patients is for the most part in artificial light, which is known to affect colour perception. However, the phenomenon of colour constancy (the perceived stability of the colour of objects, despite changes in the illuminating light) allows the eye and brain to compensate, to some extent. Colours like red, yellow, green and blue, which are processed by basic colour-opponent mechanisms, show better colour constancy than intermediate colours. These are the very colours that are involved in skin tones. A skin rash can therefore be viewed sometimes acceptably with lower-quality telemedical systems. Colour is undoubtedly important in telemedicine, but while a great deal is known about the fundamentals of colour perception from laboratory experiments, little is known about the effects of colour on the outcome of the telemedical process. The field of colour perception therefore represents a fertile area for telemedical research.
Scoring written material from the Mini-Mental State Examination: a comparison of face-to-face, fax and video-linked scoring
Authors: Ball Chris , Tyrrell Jeanne , Long Colm
Published: October 2002

We assessed the reliability of scoring written items of the Mini-Mental State Examination (MMSE) using different communication modes: face to face, fax and videoconferencing. A total of 99 MMSEs were recovered from the records of a community mental health team for the elderly. The written parts of the examination (sentence and pentagrams) were scored - in person, using a faxed copy or over the video-link - according to published criteria. Relative to in-person scoring, sentences could be scored reliably when faxed (kappa=0.80), as could pentagrams (kappa=0.71). Sentences could be reliably scored over the videoconferencing link (kappa=0.70), but pentagrams could not (kappa=0.47). Caution is required before accepting the results of scoring such tests over video-links.
Models of intracellular transport and evolution of the Golgi complex
Authors: Beznoussenko Galina V. , Mironov Alexander A.
Published: October 2002

We have performed a systematic analysis of models explaining the mechanisms of the intracellular biosecretory transport. The models assessed include not only those based on one mechanism (the dissociation model (and its individual case, the vesicular model), the progression model (and its individual cases, the cisterna maturation/progression and the carrier maturation models), and the lateral diffusion model (and its individual case, the bolus model), but also combined models of transport (the percolating‐vesicles model and the synthetic model), including several transport mechanisms. Most of these models are not able to explain recent data on the evolution of genes involved in intracellular transport and Golgi evolution. The carrier maturation model proposing that fusion of the large cargo domain with the distal (closer to the plasmalemma) compartment precedes fission of the domain from the proximal compartment exhibits the best performance in correlation with the available information on evolution of the biosecretory pathway. Anat Rec 268:226–238, 2002. © 2002 Wiley‐Liss, Inc.
Living well through chronic illness: The relevance of virtue theory to patients with chronic osteoarthritis
Authors: Swift Teresa L. , Ashcroft Richard E. , Tadd Win , Campbell Alastair V. , Dieppe Paul A.
Published: October 2002

Objective

Virtues and vices possessed by patients may affect their quality of life and how well they cope with disease. The objective of this study is to assess the relevance of the concept of virtue and vice to patients with chronic arthritis.

Methods

Aristotle's theory of virtue and vice was used to construct a guide for in‐depth interviews, carried out with 5 patients with chronic osteoarthritis. Interviews were tape recorded, transcribed, and analyzed (using Interpretative Phenomenological Analysis) for information on personal qualities or intellectual approaches that participants thought necessary to thrive in the face of chronic disease.

Results

Five main themes emerged: strength, prudence, gratitude, self‐worth, and insight into flourishing. The data on each of these is compared with Aristotle's definitions of virtues and vices.

Conclusions

Aristotle's virtue theory can be applied to the narratives of these patients with chronic osteoarthritis, and may help in understanding their coping strategies and quality of life.
Bcl‐2 rescues motoneurons from early cell death in the cervical spinal cord of the chicken embryo
Authors: Sato Noboru , Sakuma Chie , Kato Hiromi , Milligan Carolanne E. , Oppenheim Ronald W. , Yaginuma Hiroyuki
Published: October 2002

Motoneurons (MNs) in the cervical spinal cord of the chicken embryo undergo programmed cell death (PCD) between embryonic day (E) 4 and E5. The intracellular molecules regulating this early phase of PCD remain unknown. Here we show that introduction of Bcl‐2 by a replication‐competent avian retroviral vector prevented MN degeneration at E4.5, whereas the expression of the green fluorescent protein (GFP) was ineffective. Bcl‐2 expression did not affect the number of Islet‐1/2‐positive MNs at the onset of cell death (E4). However, when examined at the end of the cell death period (E5.5), the number of Islet‐1/2‐positive MNs was clearly increased in Bcl‐2‐transfected embryos compared with control and GFP‐transfected embryos. Activation of caspase‐3, which is normally observed in this early MN death, was also prevented by Bcl‐2. Thus, MNs in the cervical spinal cord appear to use intracellular pathway(s) for early PCD that is responsive to Bcl‐2. © 2002 Wiley Periodicals, Inc. J Neurobiol 53: 381–390, 2002
Planar cell polarity in the inner ear: How do hair cells acquire their oriented structure?
Authors: Lewis Julian , Davies Alex
Published: October 2002

Sensory hair cells in the ear and lateral line have an asymmetrical hair‐bundle structure, essential for their function as directional mechanotransducers. We examine four questions: (1) how does the planar asymmetry of the individual hair cell originate? (2) How are the orientations of neighboring hair cells coordinated? (3) How is the orientation of a group of hair cells controlled in relation to the ear as a whole? (4) How does the initial cell asymmetry lead to creation of the asymmetrical hair bundle? Studies of the development of hairs and bristles in Drosophila, combined with genetic data from vertebrates, suggest that the answer to questions (1) and (2) lies in asymmetries that develop at the cell cortex and at cell–cell junctions, generated by products of a set of primary planar cell polarity genes, including the transmembrane receptor Frizzled. A separate and largely independent mechanism controls asymmmetric allocation of cell fate determinants such as Numb at mitosis, in Drosophila and possibly in the ear also. Little is known about long‐range signals that might orient hair cells globally in the ear, but progress has been made in identifying a set of genes responsible for read‐out of the primary polarity specification. These genes, in flies and vertebrates, provide a link to assembly of the polarized cytoskeleton; myosin VIIA appears to belong in this group. The mechanism creating the staircase pattern of stereocilium lengths is unknown, but could involve regulation of stereocilium growth by Ca2+ ions entering via transduction channels. © 2002 Wiley Periodicals, Inc. J Neurobiol 53: 190–201, 2002
Understanding inner ear development with gene expression profiling
Authors: Chen Zheng‐Yi , Corey David P.
Published: October 2002

Understanding the development of the inner ear requires knowing the spatial and temporal pattern of gene expression, and the functions of those gene products. In the last decade, hearing research has benefited tremendously from the progress of the human and mouse genome projects, as amply illustrated by the identification of many deafness genes in both human and mouse. However, the sheer amount of information generated from the genome project has far outpaced the rate at which it is utilized. Microarray technology offers a means to quantify the expression level of transcripts at a whole‐genome scale. Cross‐tissue comparisons will identify genes unique to the inner ear, which will expedite the identification of new deafness genes. Microdissection and subtraction after ablation of cell types can reveal genes expressed in certain cells, such as hair cells. Expression profiling of both inner ear and other tissues, under a variety of conditions (such as during development, with drug treatment or in knock‐out animals), can be used for cluster analysis to group genes of similar expression. Coexpression can suggest functional pathways and interactions between known genes, and can identify new genes in a structure or pathway. In this review we give examples for both transcription factors and cochlear structures. © 2002 Wiley Periodicals, Inc. J Neurobiol 53: 276–285, 2002
A review of inner ear fate maps and cell lineage studies
Authors: Kil Sung‐Hee , Collazo Andres
Published: October 2002

A renewed interest in the development of the inner ear has provided more data on the fate and cell lineage relationships of the tissues making up this complex structure. The inner ear develops from a simple ectodermal thickening of the head called the otic placode, which undergoes a great deal of growth and differentiation to form a multichambered nonsensory epithelium that houses the six to nine sensory organs of the inner ear. Despite a large number of studies examining otic development, there have been surprisingly few fate maps generated. The published fate maps encompass four species and range from preotic to otocyst stages. Although some of these studies were consistent with a compartment and boundary model, other studies reveal extensive cell mixing during development. Cell lineage studies have been done in fewer species. At the single cell level the resulting clones in both chicks and frogs appear somewhat restricted in terms of distribution. We conclude that up until late placode stages there are no clear lineage restriction boundaries, meaning that cells seem to mix extensively at these early stages. At late placode stages, when the otic cup has formed, there are at least two boundaries located dorsally in the forming otocyst but none ventrally. These conclusions are consistent with all the fate maps and reconciles the chick and frog data. These results suggest that genes involved in patterning the inner ear may have dynamic and complex expression patterns. © 2002 Wiley Periodicals, Inc. J Neurobiol 53: 129–142, 2002
Mycothiol-Deficient
Mycobacterium smegmatis
Mutants Are Hypersensitive to Alkylating Agents, Free Radicals, and Antibiotics
Authors: Rawat Mamta , Newton Gerald L. , Ko Mary , Martinez Gladys J. , Fahey Robert C. , Av-Gay Yossef
Published: October 2002

Mycothiol (MSH; 1
d
-
myo
-inosityl 2-[
N
-acetyl-
l
-cysteinyl]amido-2-deoxy-α-
d
-glucopyranoside) is the major low-molecular-weight thiol produced by mycobacteria. Mutants of
Mycobacterium smegmatis
mc
2
155 deficient in MSH production were produced by chemical mutagenesis as well as by transposon mutagenesis. One chemical mutant (mutant I64) and two transposon mutants (mutants Tn1 and Tn2) stably deficient in MSH production were isolated by screening for reduced levels of MSH content. The MSH contents of transposon mutants Tn1 and Tn2 were found to be less than 0.1% that of the parent strain, and the MSH content of I64 was found to be 1 to 5% that of the parent strain. All three strains accumulated 1
d
-
myo
-inosityl 2-deoxy-α-
d
-glucopyranoside to levels 20- to 25-fold the level found in the parent strain. The cysteine:1
d
-
myo
-inosityl 2-amino-2-deoxy-α-
d
-glucopyranoside ligase (MshC) activities of the three mutant strains were ≤2% that of the parent strain. Phenotypic analysis revealed that these MSH-deficient mutants possess increased susceptibilities to free radicals and alkylating agents and to a wide range of antibiotics including erythromycin, azithromycin, vancomycin, penicillin G, rifamycin, and rifampin. Conversely, the mutants possess at least 200-fold higher levels of resistance to isoniazid than the wild type. We mapped the mutation in the chemical mutant by sequencing the
mshC
gene and showed that a single amino acid substitution (L205P) is responsible for reduced MSH production and its associated phenotype. Our results demonstrate that there is a direct correlation between MSH depletion and enhanced sensitivity to toxins and antibiotics.
Biological Cost of Rifampin Resistance from the Perspective of
Staphylococcus aureus
Authors: Wichelhaus Thomas A. , Böddinghaus Boris , Besier Silke , Schäfer Volker , Brade Volker , Ludwig Albrecht
Published: October 2002

Resistance determinants that interfere with normal physiological processes in the bacterial cell usually cause a reduction in biological fitness. Fitness assays revealed that 17 of 18 in vitro-selected chromosomal mutations within the
rpoB
gene accounting for rifampin resistance in
Staphylococcus aureus
were associated with a reduction in the level of fitness. There was no obvious correlation between the level of resistance to rifampin and the level of fitness loss caused by
rpoB
mutations. Among 23 clinical rifampin-resistant
S. aureus
isolates from six countries, only seven different
rpoB
genotypes could be identified, whereby the mutation 481His→Asn was present in 21 (91%) of these 23 isolates. The mutation 481His→Asn, in turn, which confers low-level rifampin resistance on its own, was not shown to be associated with a cost of resistance in vitro. The restriction to distinct mutations that confer rifampin resistance in vivo, as demonstrated here, appears to be determined by the Darwinian fitness of the organisms.
Proinflammatory and Cytotoxic Effects of Hexadecylphosphocholine (Miltefosine) against Drug-Resistant Strains of
Trypanosoma cruzi
Authors: Saraiva Victor B. , Gibaldi Daniel , Previato José O. , Mendonça-Previato Lucia , Bozza Marcelo T. , Freire-de-Lima Célio G. , Heise Norton
Published: October 2002

The increased resistance of the protozoan parasite
Trypanosoma cruzi
to nitro derivatives is one of the major problems for the successful treatment of Chagas' disease. In the present study, we have tested the effects of 1-
O
-hexadecylphosphocholine (miltefosine) against strains of
T. cruzi
that are partially resistant (strain Y) and highly resistant (strain Colombiana) to the drugs in clinical use. As expected, epimastigotes of strain Colombiana showed higher levels of resistance to benznidazole than those of strain Y. However, the level of resistance to miltefosine was the same for both strains. This alkylphospholipid was also extremely toxic against intracellular amastigotes of both strains. This ether-lipid analogue induced in a dose-dependent manner the production of tumor necrosis factor alpha and nitric oxide (NO) radicals by infected and noninfected macrophages, suggesting that miltefosine may activate macrophages in vitro. Nevertheless, the cytotoxic effect of miltefosine against intracellular amastigotes was independent of the amount of NO produced by the infected macrophages since the same dose-response curves for miltefosine were observed when the NO production was blocked by the NO synthase inhibitor
N
G
-monomethyl-
l
-arginine monoacetate. Preliminary in vivo studies with BALB/c mice infected with strain Y indicated that oral miltefosine promoted survival and reduced the parasitemia to levels comparable to those observed when benznidazole was used. Four months after treatment, no parasites were detected in the blood or spleen tissue sections maintained in culture. Together, these results support the hypothesis that miltefosine may be used for the treatment of Chagas' disease, including cases caused by resistant strains of
T. cruzi
.
Histone Deacetylase Inhibitors Enhance
Candida albicans
Sensitivity to Azoles and Related Antifungals: Correlation with Reduction in
CDR
and
ERG
Upregulation
Authors: Smith W. Lamar , Edlind Thomas D.
Published: October 2002

Histone acetylation and deacetylation play important roles in eukaryotic gene regulation. Several histone deacetylase (HDA) inhibitors have been characterized, including trichostatin A (TSA), apicidin, and sodium butyrate. We tested their effects on
Candida albicans
in vitro growth, heat sensitivity, and germ tube formation; minimal effects were observed. However, there was a dramatic effect of TSA on
C. albicans
sensitivity to the azoles fluconazole, itraconazole, and miconazole. Similar effects were observed with other HDA inhibitors and with the antifungals terbinafine and fenpropimorph, which target, as do azoles, enzymes in the ergosterol biosynthetic pathway. In contrast, HDA inhibitors had minimal effect on the activities of amphotericin B, flucytosine, and echinocandin, which have unrelated targets. Specifically, addition of 3 μg of TSA/ml lowered the itraconazole MIC for five susceptible
C. albicans
isolates an average of 2.7-fold at 24 h, but this increased to >200-fold at 48 h. Thus, the primary effect of TSA was a reduction in azole trailing. TSA also enhanced itraconazole activity against
Candida parapsilosis
and
Candida tropicalis
but had no effect with four less related yeast species. To examine the molecular basis for these effects, we studied expression of
ERG
genes (encoding azole and terbinafine targets) and
CDR/MDR1
genes (encoding multidrug transporters) in
C. albicans
cells treated with fluconazole or terbinafine with or without TSA. Both antifungals induced to various levels the expression of
ERG1
,
ERG11
,
CDR1
, and
CDR2
; addition of TSA reduced this upregulation 50 to 100%. This most likely explains the inhibition of azole and terbinafine trailing by TSA and, more generally, provides evidence that trailing is mediated by upregulation of target enzymes and multidrug transporters.
Erythromycin Resistance in
Borrelia burgdorferi
Authors: Terekhova Darya , Sartakova Marina L. , Wormser Gary P. , Schwartz Ira , Cabello Felipe C.
Published: October 2002

Susceptibility testing of laboratory strains and clinical isolates of
Borrelia burgdorferi
indicates that resistance to erythromycin is present in them. Evaluation of the MICs, minimal bactericidal concentrations, and kinetics of bacterial killing of erythromycin suggests that this resistance is increased by preexposure to the antibiotic, is dependent on inoculum size, and may be the result of selection of subpopulations of bacterial cells with increased resistance.
Biologically induced clogging of a granular medium permeated with synthetic leachate
Authors: Rowe R K , VanGulck J F , Millward S C
Published: October 2002

The results of a laboratory column test conducted to gain insight regarding the clogging mechanisms within porous media are presented. Tests were conducted under saturated, anaerobic conditions using synthetic leachate that models Keele Valley Landfill (KVL) leachate in chemical compositions but has negligible suspended solids and bacterial concentrations compared with KVL leachate. Comparisons were made between tests conducted with synthetic leachate and similar column tests conducted with KVL leachate to assess the presence of suspended solids and bacterial loading on the rate of clogging. It is shown that the synthetic leachate columns behaved similarly to the KVL leachate columns in terms of nutrients removed from the leachate as it passed through the porous media and clog properties (bulk densities and chemical composition). Excessive microbially induced clogging near the influent end of the column (but likely near the collection pipe in a field situation) resulted in a decrease in drainable porosity to less than 10% of the initial value and a decrease in hydraulic conductivity by seven orders of magnitude. Key words: leachate collection, clogging, porous media, anaerobic, laboratory study.
Factors affecting intra- and inter-specific variations in the difference between alert distances and flight distances for birds in forested habitats
Authors: Fernández-Juricic E , Jimenez M D , Lucas E
Published: October 2002

Studies of escape from predators have usually focused on fleeing. We studied intra- and inter-specific variations in a previous level of decision-making during predatorprey encounters by determining the difference between the distance at which a predator is detected and the distance at which the prey flees from the predator (buffer distance). We measured buffer distances of four bird species (ground foragers) living in forested habitats (wooded recreational parks) to approaching humans. Buffer distances increased with group size and temperature, and this was probably related to dilution of the predation risk and a higher risk of heat stress, respectively. Buffer distances decreased with shrub and coniferous cover, probably because of increased visual obstruction, and increased with tree height, probably because of the increased security provided by taller trees. Grass cover increased buffer distances of wood pigeons (Columba palumbus) but decreased those of house sparrows (Passer domesticus) and magpies (Pica pica); this may be related to higher food availability, i.e., vegetation in grassy areas for wood pigeons and food left by humans in areas with bare ground for house sparrows and magpies. Buffer distances of blackbirds (Turdus merula) and house sparrows were greater in highly visited parks, which may be related to habituation. Finally, larger species showed greater buffer distances, landed farther away, used higher landing substrates (trees), and flew higher, probably because they need to ensure a certain margin of security from predators. Alternatively, the increased buffer distances of large species may be related to the increasing energy expenditure of flight. The buffer distance appears to be a good indicator of tolerance toward predators and (or) risk taken by prey after detecting predators.
Is prolactin responsible for avian, saurian, and mammalian relapse and periodicity of fever in malarial infections?
Authors: Pearson Roy Douglas
Published: October 2002

P.C.C. Garnham came to Toronto nearly 35 years ago to see if he, and the laboratory of A.M. Fallis, could unravel the enigma of "relapsing" malaria-like infections in migrating ducks (to Algonquin Park, Ontario). At the time, not enough was known about the endocrinology of avian migration and reproduction. Now a growing body of indirect evidence seems to point to a role for prolactin in many of the uniquely pathologic phenomena witnessed in malarial infections. Arguments in favour of the involvement of prolactin, as both a developmental hormone and a proinflammatory cytokine, in the pathology of relapse, fever, anaemia, and maternal malaria are presented in the hope that experiments to test such involvement will be designed.
PARTICLE IDENTIFICATION IN THE DYNAMICAL STRING-PARTON MODEL OF RELATIVISTIC HEAVY-ION COLLISIONS
Authors: MALOV D. E. , UMAR A. S. , ERNST D. J. , DEAN D. J.
Published: October 2002

The dynamical string-parton model for relativistic heavy-ion collisions is generalized to include particle identification of the final-state hadrons by phenomenologically quantizing the masses of the classical strings which result from string breaking. General features of the Nambu-Gotō strings are used to motivate a model that identifies a mass window near the physical mass of a meson, and does not allow the string to decay further if its mass falls within the window. Data from e+e- collisions in the region [Formula: see text] to 30 GeV are well reproduced by this model.
NEUTRON-PROTON INTERACTION IN ODD-ODD SPHERICAL NUCLEI NEAR 208PB
Authors: ALEXA PETR , KVASIL JAN , SHELINE RAYMOND K.
Published: October 2002

A total of 74 levels from 21 multiplets of the nuclei 206 Tl , 208 Tl , 208 Bi , and 210 Bi have been calculated with a Generalized Intermediate Coupling Model, with Gaussian and delta potentials with and without an interaction between octupole phonon and odd nucleons. The goodness of fit is compared with that of other calculations of Molinari et al. and Schiffer and True. It is quite clear that the calculations work well in spite of the fact that they are required to fit simultaneously odd-odd nuclei with neutron and proton shells which differ by principal harmonic oscillator quantum numbers Δ N = +1.
WIDE-ANGLE α-t COINCIDENCE MEASUREMENT IN THE BREAKUP OF 7Li ON 27Al
Authors: MADHUSOODHANAN T. , MANDAL SAMIT , SATHYAVATHIAMMA M. P. , RAMANI  , PUTTASWAMY N. G. , MUDHOLE T. S. , MANDAL A. , AVASTHI D. K. , DATTA S. K. , SHYAM R.
Published: October 2002

We have performed wide-angle in-plane coincidence measurements of the alpha particles and tritons emitted in the 48-MeV 7 Li projectile breakup reaction on 27 Al . The data have been analyzed using the post-form distorted-wave Born-approximation (DWBA) theory of breakup reactions where Coulomb and nuclear breakup as well as their interference terms are included. The theory is able to provide a good description of the experimental data particularly at large relative angles between the fragments. The interference between the Coulomb and nuclear breakup modes is found to be significant.
Prognostic value of enhanced bone marrow angiogenesis in early B-cell chronic lymphocytic leukemia
Authors: Molica Stefano , Vacca Angelo , Ribatti Domenico , Cuneo Antonio , Cavazzini Francesco , Levato Domenico , Vitelli Gaetano , Tucci Luigi , Roccaro Aldo M. , Dammacco Franco
Published: October 2002

Because tumor progression is angiogenesis-dependent, angiogenesis density was investigated by immunohistochemistry and computed image analysis in bone marrow (BM) biopsies of 45 newly diagnosed patients with Binet stage A B-cell chronic lymphocytic leukemia (BCLL) and correlated to upstaging and progression-free survival during a 40-month follow-up period. Their microvessel areas and counts were significantly higher than those of patients with anemia due to iron or vitamin B12deficiencies. A cutoff value of 0.90 mm2 × 10−2 or greater of the microvessel area identified patients with earlier upstaging and shorter progression-free survival. When the cutoff was applied to the Rai subclassification, both Rai 0 and Rai I-II patients who upstaged and shortened the progression-free survival were classified correctly. Information of this type was not given by the microvessel counts. The cutoff did not correlate with other predictors representative of tumor mass or disease progression. The microvessel area correlated with the expression of angiogenic vascular endothelial growth factor (VEGF) by tumor tissue, and serum levels of VEGF were found to be of prognostic value. A causal relationship between risk of progression and BM angiogenesis in BCLL is suggested. A risk stratification inside Rai is proposed. The prognostic usefulness of BM angiogenesis in patients with BCLL is envisaged.
Regulation of thymic epithelium by keratinocyte growth factor
Authors: Erickson Matthew , Morkowski Stanislaw , Lehar Sophie , Gillard Geoffrey , Beers Courtney , Dooley James , Rubin Jeffrey S. , Rudensky Alexander , Farr Andrew G.
Published: October 2002

Here we demonstrate that keratinocyte growth factor (KGF) and FGFR2IIIb signaling can affect development and function of thymic epithelium (TE) and that αβ-lineage thymocytes contribute to intrathymic levels of KGF. Thymocyte expression of KGF is developmentally regulated, being undetectable in CD3−4−8− thymocytes and expressed at highest levels by mature CD4 or CD8 thymocytes. Exposure of thymocyte-depleted fetal thymic lobes to KGF resulted in reduced thymic epithelial expression of class II major histocompatibility complex (MHC), invariant chain (Ii), and cathepsin L (CatL) molecules involved in thymocyte-positive selection and also stimulated expression of the cytokines interleukin 6 (IL-6) and thymic stromal-derived lymphopoietin (TSLP), while having little effect on IL-7 or stem cell factor expression. Within intact fetal thymic organ culture (FTOC), exogenous KGF impairs the generation of CD4 thymocytes. Two lines of evidence point to responsiveness of the medullary TE compartment to KGF and FGFR2IIIb signaling. First, the medullary compartment is expanded in intact FTOC exposed to KGF in vitro. Second, in the RAG-deficient thymus, where the thymocytes do not express detectable levels of KGF message, the hypoplastic medullary TE compartment can be expanded by administration of recombinant KGF in vivo. This expansion is accompanied by restoration of the normal profile of medullary TE–associated chemokine expression in the RAG2−/−thymus. Collectively, these findings point to a role for KGF and FGFR signaling in the development and function of thymic epithelium.
Single-chain antigen recognition receptors that costimulate potent rejection of established experimental tumors
Authors: Haynes Nicole M. , Trapani Joseph A. , Teng Michèle W. L. , Jackson Jacob T. , Cerruti Loretta , Jane Stephen M. , Kershaw Michael H. , Smyth Mark J. , Darcy Phillip K.
Published: October 2002

Tumor cells are usually weakly immunogenic as they largely express self-antigens and can down-regulate major histocompatability complex/peptide molecules and critical costimulatory ligands. The challenge for immunotherapies has been to provide vigorous immune effector cells that circumvent these tumor escape mechanisms and eradicate established tumors. One promising approach is to engineer T cells with single-chain antibody receptors, and since T cells require 2 distinct signals for optimal activation, we have compared the therapeutic efficacy of erbB2-reactive chimeric receptors that contain either T-cell receptor zeta (TCR-ζ) or CD28/TCR-ζ signaling domains. We have demonstrated that primary mouse CD8+ T lymphocytes expressing the single-chain Fv (scFv)–CD28-ζ receptor have a greater capacity to secrete Tc1 cytokines, induce T-cell proliferation, and inhibit established tumor growth and metastases in vivo. The suppression of established tumor burden by cytotoxic T cells expressing the CD28/TCR-ζ chimera was critically dependent upon their interferon gamma (IFN-γ) secretion. Our study has illustrated the practical advantage of engineering a T-cell signaling complex that codelivers CD28 activation, dependent only upon the tumor's expression of the appropriate tumor associated antigen.
Identification of the hemangioblast in postnatal life
Authors: Pelosi Elvira , Valtieri Mauro , Coppola Simona , Botta Rosanna , Gabbianelli Marco , Lulli Valentina , Marziali Giovanna , Masella Barbara , Müller Robert , Sgadari Cecilia , Testa Ugo , Bonanno Giuseppina , Peschle Cesare
Published: October 2002

Postnatal CD34+ cells expressing vascular endothelial growth factor receptor 2 (KDR) generate hematopoietic or endothelial progeny in different in vitro and in vivo assays. Hypothetically, CD34+KDR+ cells may comprise hemangioblasts bipotent for both lineages. This hypothesis is consistent with 2 series of experiments. In the first series, in clonogenic culture permissive for hematopoietic and endothelial cell growth, CD34+KDR+ cells generate large hemato-endothelial (Hem-End) colonies (5% of seeded cells), whereas CD34+KDR− cells do not. Limiting-dilution analysis indicates that Hem-End colonies are clonally generated by single hemangioblasts. Sibling cells generated by a hemangioblast, replated in unicellular culture, produce either hematopoietic or Hem-End colonies, depending on the specific culture conditions. Identification of endothelial cells was based on the expression of VE-cadherin and endothelial markers and with lack of CD45 and hematopoietic molecules, as evaluated by immunofluorescence, immunocytochemistry, and reverse transcription–polymerase chain reaction. Furthermore, endothelial cells were functionally identified using low-density lipoprotein (LDL) uptake and tube-formation assays. In the second series, to evaluate the self-renewal capacity of hemangioblasts, single CD34+KDR+ cells were grown in 3-month extended long-term culture (ELTC) through 3 serial culture rounds—that is, blast cells generated in unicellular ELTC were reseeded for a subsequent round of unicellular ELTC. After 9 months, 10% blasts from tertiary ELTC functioned as hemangioblasts and generated macroscopic Hem-End colonies in clonogenic culture. These studies identified postnatal hemangioblasts in a CD34+KDR+ cell subset, endowed with long-term proliferative potential and bilineage differentiation capacity. Although exceedingly rare, hemangioblasts may represent the lifetime source/reservoir for primitive hematopoietic and endothelial progenitors.
Occurrence of hyperhomocysteinaemia in cardiovascular, haematology and nephrology patients: contribution of folate
Authors: Onnelly James G D , Isotalo Phillip A
Published: October 2002

We investigated the contribution of plasma folate deficiency to hyperhomocysteinaemia in selected patient groups. Based on our observations, we have determined a lower folate reference interval cut-off using homocysteine as a metabolic marker of folate deficiency. Four hundred and twenty-five consecutive plasma specimens from cardiology ( n=120), haematology ( n=190) and nephrology ( n=115) patients were analysed for homocysteine and plasma folate concentrations. Healthy volunteers were used as controls ( n=117). We observed elevated homocysteine values above our upper reference limit of 13 µmol/L in 20·1%, 28·4% and 74·8% of the cardiology, haematology and nephrology patients, respectively. All but 1·9% of the patients had plasma folate values greater than the lower reference interval limit (3·4 nmol/L) for our folate assay. The percentage of patients from cardiology and haematology clinics who were hyperhomocysteinaemic and had folate values > 15 nmol/L was 5·0% and 4·2% , respectively. In contrast, 58% of our nephrology patients with folate values > 15 nmol/L were hyperhomocysteinaemic. In all three groups, an inverse relationship was found between folate and homocysteine. The folate/homocysteine ratios in the patient groups were approximately one-third of the values observed in our control group. Folate deficiency appears to be the primary cause of hyperhomocysteinaemia in our cardiology and thrombosis patients. However, severe folate deficiency appears to be uncommon. The majority of our nephrology patients are hyperhomocysteinaemic without an apparent folate deficiency. We conclude that raising the lower reference interval cut-off for folate to 15 nmol/L would help to identify individuals at risk for hyperhomocysteinaemia in our non-uraemic patient population. Increasing folate supplementation to maintain a plasma concentration above 15 nmol/L in cardiac, thrombosis and renal patients would greatly reduce the occurrence of hyperhomocysteinaemia in these patients.
Total homocysteine measurement in clinical practice
Authors: Rasmussen Karsten , Møller Jan
Published: October 2002

This review will primarily address methodological aspects of homocysteine measurement, highlighting changes since the subject was comprehensively reviewed in 1993, and will bring together practical information of relevance to laboratory planning or to providing an analytical service including homocysteine measurement. Because the physiological state of the patient during blood collection is often neglected, and because it has become apparent that the bloodsampling procedure may contribute considerably more variation to measurement of homocysteine than the total variation of the analytical procedures, the review will pay particular attention to the critical roles of controlled blood collection and sample processing.
Hyperfibrinogenaemia did not improve after treating hyperglycaemia in Chinese type 2 diabetic patients
Authors: Ko Gary T C , Chan Juliana C N , Tsang Lynn L W , Cockram Clive S
Published: October 2002

Diabetic patients have higher cardiovascular risk than non-diabetic subjects, and fibrinogen has been reported to be one of the independent predictors for diabetic vascular complications. We examined 101 subjects (24 men, 77 women) who were newly diagnosed with type 2 diabetes. Thirty non-diabetic subjects were recruited as controls. The mean (standard deviation, SD) baseline fibrinogen concentrations in men and women were 3·87 (1·17) and 3·42 (1·00) g/L, respectively (not significantly different). Of these 101 subjects, 70 were treated with diet alone and 31 were treated with oral agents. After a mean (SD) follow-up period of 2·38 (0·63) years, there was an 18·5% increase in the fibrinogen concentration from 3·53 (1·06) g/L at baseline to 3·97 (1·07) g/L at follow-up ( P<0·001). The normal subjects had a mean (SD) follow-up period of 1·17 (0·38) years, and showed no significant change in their fibrinogen concentrations from 3·49 (0·90) g/L at baseline to 3·15 (0·61) g/L at follow-up. In the 101 diabetic subjects, only changes in plasma triglyceride correlated with the changes in fibrinogen concentration. Using multivariate analysis with age, sex, duration of diabetes, baseline and changes in body mass index, blood pressure, glycaemic and lipid parameters as independent variables ( R2=0·106, F=6·840, P=0·011), triglyceride (β=0·282, P=0·011) was identified as the only independent variable that predicted the changes in the fibrinogen concentrations. Improved glycaemic control was not accompanied by a reduction in plasma fibrinogen concentration.
Comparison of Abbott AxSYM, Behring Opus Plus, DPC Immulite and Ortho-Clinical Diagnostics Vitros ECi for measurement of cardiac troponin I
Authors: Kao Jau-Tsuen , Wong I-Li , Lee Jeen-Yih , Chen Ruey-Chean
Published: October 2002

Myocardial infarction is a common cause of morbidity and mortality in patients with chest pain. The presence of human cardiac troponin I (cTnI) in serum is considered to be a highly specific biochemical marker of acute myocardial infarction. In this study we compare the performances of the Abbott AxSYM, Behring Opus Plus, DPC Immulite and Ortho-Clinical Diagnostics Vitros ECi for the measurement of cTnI. The first two methods use a fluorogenic enzyme-linked immunoassay, whereas the last two use chemiluminescent immunometric assays. All procedures are completely automated. Total percentage coefficients of variation using pooled sera ranged from 5·9 to 6·5% for the AxSYM, 14·4 to 25·6% for the Opus, 6·9 to 9·8% for the Immulite and 4·5 to 5·2% for the Vitros ECi method. The closest correlation between methods, obtained from 120 fresh serum samples, was observed between the Vitros ECi and the Immulite methods, with r=0·99, and the regression line was Immulite cTnI=1·505 (95% confidence interval 1·474-1·536) x Vitros cTnI-0·154 (-0·702 to 0·394). Receiver operating characteristic curves were nearly identical for all assays, and the areas under the curves were 0·972, 0·927, 0·967 and 0·969 for the AxSYM, Opus, Immulite and Vitros ECi methods, respectively. There was a significant difference between the AxSYM and Opus methods ( P=0·036).
Investigation of applicability of a mid-infrared spectroscopic method using an attenuated total reflection accessory and a new near-infrared transmission method for determination of faecal fat
Authors: Volmer Marcel , Kingma Anneke W , Borsboom Peter C F , Wolthers Bert G , Kema Ido P
Published: October 2002

In many laboratories, the titrimetric method of Van de Kamer is used for the analysis of faecal fat content of patients suspected of steatorrhoea. We investigated the applicability of a mid-infrared (MIR) spectroscopic method, using an attenuated total reflection (ATR) accessory, and a new near-infrared (NIR) spectroscopic method. For the NIR method, sealed plastic bags containing the stool samples were used as transmission cells. Standardization was obtained using a previously described MIR method, with a NaCl flow-cell, as reference method. Partial least-squares regression was used for the calibration of each method. Full cross-validation of the calibration set was used for the internal validation of each method. Fifteen per cent of the stool samples could not be estimated with the ATR method within reasonable accuracy limits compared with the reference. The standard error of prediction of the NIR method was 1·1g/dL. We conclude that the new NIR method is a promising technique for routine use. However, further experiments need to be done with triplicate measurements of each sample and the use of an external validation set.
The ischaemic lactate-ammonia test
Authors: Livingstone Callum , Chinnery Patrick F , Turnbull Douglass M
Published: October 2002

The ischaemic lactate-ammonia test is widely used for investigating patients with muscle pain and fatigue. It involves measuring plasma lactate and ammonia produced as a result of forearm exercise under ischaemic conditions in a fasted subject. Its clinical use is to screen patients with muscle complaints for disorders of carbohydrate metabolism, in particular to identify those in whom further investigation may provide useful diagnostic information. There is a wide variety of methods described, reflecting attempts to optimize the response and hence the diagnostic value of the test. Although it is often considered a general screening test for metabolic muscle disease, the situations in which it is useful are specific. Here we review the use of the test and present the results of an audit of its use in our departments.
Analysis of 4-methylthioamphetamine in clinical specimens
Authors: Elliott Simon P
Published: October 2002

There has been much publicity, particularly in Europe, regarding a new phenylethylamine-based compound called 4-methylthioamphetamine (4-MTA), also known as para-methylthioamphetamine (p-MTA), MTA or 'Flatliner'. Chemically, 4-MTA is an amphetamine derivative and is a potent, non-neurotoxic serotoninreleasing agent and reversible inhibitor of rat monoamine oxidase-A. Its effects, therefore, appear different from those of amphetamine.

Analysis of various plasma and urine specimens in three clinical cases implicating 'Ecstasy' ingestion revealed the presence of 4-MTA. Presumed metabolites were also detected, with one compound identified as being 4-MTA sulphoxide. The concentrations of 4-MTA measured in the plasma ranged from 0·131mg/L to 0·760mg/L. In one patient the 4-MTA concentration was determined in a series of plasma samples and this allowed a presumptive half-life of approximately 7h to be estimated. This paper describes the first reported data regarding possible pharmacokinetics of 4-MTA in humans and presents the first reported non-fatal instances of 4-MTA intoxication in the UK.
Effect of ambient temperature on analytical and clinical performance of a blood glucose monitoring system: Omnitest Sensor glucose meter
Authors: Nawawi H , Sazali B S , Kamaruzaman B H , Yazid T N , Jemain A A , Ismail F , Khalid B A K
Published: October 2002

The effect of ambient temperature on the analytical and clinical performance of a glucose meter was examined. A total of 114 venous whole blood samples were analysed for glucose by a reference method, and by a glucose meter at 21-22°C, room temperatures, 26-27°C and 33-34°C. Glucose meter readings at each temperature were compared with the reference values and evaluated by analysis of variance, Spearman's correlation, the percentage of glucose meter readings within ± 10% of the reference value and error grid analysis. Analysis of covariance was used to determine the effect of temperature on glucose meter readings. There were no significant differences in the glucose meter readings and in accuracy of the meter readings between different temperatures. Temperature was not a significant independent determinant of the glucose meter readings. For each glucose concentration, the precision of the meter and clinical performance were comparable between the different temperatures. In conclusion, ambient temperature does not affect the accuracy, precision and clinical performance of the Omnitest Sensor.
Point-of-care testing of blood glucose in the neonatal unit using the AVL Omni 9 analyser
Authors: Newman Julie D , Pecache Nerissa S , Barfield Charles P , Balazs Nicholas DH
Published: October 2002

Background: Blood glucose measurements in newborns at risk of hypoglycaemia are an essential part of their medical management. Blood glucose measurements obtained by point-of-care testing using an AVL Omni 9 blood gas and metabolite analyser were compared with those obtained in the central laboratory using a Dade Dimension RXL analyser.

Methods: Blood glucose was measured at the point of care by nursing staff using an AVL Omni 9 blood gas and metabolite analyser and compared to results obtained in the central laboratory using a DADE Dimension RXL analyser. In total, 123 samples were taken from 114 babies admitted to the neonatal unit.

Results: The limits of agreement between the AVL Omni 9 and the central laboratory were 0·0±0·6 mmol/L for glucose values between 0·5 and 13 mmol/L. Regression analysis showed: AVL Omni 9 glucose = 0·977 x plasma glucose+0·14. There was also a good correlation ( r=0·92) between the AVL Omni 9 and the DADE Dimension RXL analyser for glucose values <3 mmol/L. The limits of agreement for the AVL Omni 9 when compared with the DADE Dimension RXL analyser were -0·1±0·5 mmol/L.

Discussion: Point-of-care testing of blood glucose using the AVL Omni 9 blood gas and metabolite analyser is a reliable means of measuring blood glucose and has the advantage of providing a fast result using small volumes of blood.
Surgical approach to a giant fibrolipoma of the supraglottic larynx
Authors: Sakamoto Kikuo , Mori Kazunori , Umeno Hirohito , Nakashima Tadashi
Published: October 2002

This paper describes the surgical procedures for a fibrolipoma that first appeared as a giant tumour in the hypopharynx and extended to the cardiac antrum of the oesophagus. At the initial surgery, a pedunculated tumour originating from the left arytenoid of the larynx was found to occupy the cervical as well as thoracic oesophagus and was thus removed through a lateral pharyngectomy. A histological examination revealed fibrolipoma. However there was a recurrence of the tumour in the arytenoid and the patient suffered from dyspnoea. In addition, a submucosal tumour was also found in the left false vocal fold. At the second surgery, the masses in the arytenoid and false vocal fold were subtotally removed without damaging the mucosa. The mucosa of the arytenoid was sutured to the thyropharyngeal muscle on the same side and the arytenoid swelling disappeared almost completely. The post-operative course has been uneventful for more than two years.