bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lithium has No Direct Effect on Cardiac Function in the Isolated, Perfused Rat Heart
Authors: Linakis James G. , Savitt Daniel L. , Schuyler Joy E. , Simon Peter M. , Raymond Richard M. 
Published: October 2004

Abstract:To determine if lithium exerts direct cardiac toxicity, using an isolated, perfused rat heart model, paced and unpaced beating rat hearts were perfused with Krebs‐Henseleit bicarbonate solution and left ventricular pressures were measured via a balloon‐tipped catheter positioned in the left ventricle via the mitral valve. Following a stabilization period, hearts were then perfused with Krebs‐Henseleit bicarbonate solution containing 1, 10, and 100 mM ionized lithium chloride or lithium carbonate in an antecedent dose‐response protocol and perfused for 10 min. at each dose. To control for the possibility of osmotic effects from the high dose of lithium, an additional group was studied in which hearts were perfused with Krebs‐Henseleit bicarbonate solution for an initial stabilization period, then perfused for an additional 20 min. with Krebs‐Henseleit bicarbonate solution alone, and finally with Krebs‐Henseleit bicarbonate solution containing mannitol (200 mOsm/l) for 10 min. Lithium did not have any effect on left ventricular peak systolic pressure, left ventricular end diastolic pressure, heart rate or coronary haemodynamics at concentrations of 1 or 10 mM. At 100 mM LiCl and Li2CO3, left ventricular peak systolic pressure decreased transiently during the first minute of lithium infusion, but recovered significant function by 10 min. Heart rate decreased significantly by 10 min. of infusion. These effects were also seen in the osmotic controls and thus do not appear to be a direct effect of lithium. At the doses tested, lithium had no direct effect on cardiac function which could not be explained by an osmotic effect.
Supernatants from Macrophages Stimulated with Microcystin‐LR Induce Electrogenic Intestinal Response in Rabbit Ileum
Authors: Rocha Marcos F. G. , Sidrim José J. C. , Soares Alberto M. , Jimenez George C. , Guerrant Richard L. , Ribeiro Ronaldo A. , Lima Aldo A. M. 
Published: October 2004

Abstract:Microcystin‐LR is a cyclic heptapeptide hepatotoxin produced by the cyanobacterium Microcystis aeruginosa. This microorganism often forms toxic blooms in freshwater lakes and reservoirs for drinking water supply, producing serious disorders in humans and animals. Some have suggested that certain biological activities of microcystin may depend upon the stimulation of immune cells. Therefore, the aims of this research were to examine electrogenic intestinal secretion, in vitro, caused by the supernatants from macrophages stimulated with microcystin‐LR, as well as to investigate the presence of interleukin‐1β and tumour necrosis factor‐α in these supernatants. We found that the supernatants of macrophages stimulated with microcystin‐LR (0.1, 0.3 and 1.0 μg/ml) caused electrogenic intestinal effects (change in short‐circuit currents (Δ SCC)=57.6, 50.8 and 73.3, respectively, versus control=19.6 μA.cm−2) in a time‐dependent way (microcystin‐LR (1.0 μg/ml)=63.2, 108.8, 120.4 and 132.3 μA.cm−2 at time 0, 40, 50 and 60 min., respectively). In addition, the intestinal secretory activity present in these supernatants was blocked (57%) by the prior treatment of macrophages with dexamethasone. We also demonstrated that microcystin‐LR (0.1, 0.3 and 1.0 μg/ml) is capable of stimulating the synthesis of tumour necrosis factor‐α (375.4, 369.0 and 610.8 pg/ml, respectively, versus control=165.0 pg/ml) and interleukin‐1β (198.9, 189.3 and 522.1 pg/ml, respectively, versus control=39.7 pg/ml). These findings demonstrate that microcystin‐LR induces the release of interleukin‐1β and tumour necrosis factor‐α by peritoneal macrophages in vitro, and that the supernatants from these macrophages induce electrogenic secretion in rabbit ileal mucosa.
Citizen Response to Disasters: a Survey of Literature and Some Practical Implications
Authors: Helsloot I. , Ruitenberg A. 
Published: October 2004

It is most likely that the modern citizen responds to disasters in the same fashion as his ancestor. Contrary to widespread belief, citizens do not panic in disaster situations. In fact, research into different aspects of citizen response shows that most citizens act in a rather rational way. Indeed, citizens often prove to be the most effective kind of emergency personnel. Disaster evaluations invariably show that most lives are actually saved by the ‘average’ citizen. On the other hand, it seems little can be done to improve citizen preparedness. A modern western citizen is not likely to invest time or money in preparing for ‘acceptable’ risks.The above results stem for the greater part from research already conducted as long ago as the nineteen‐eighties. Limitations and implications however seem as yet unclear. One important limitation is the cultural bias in most studies. One important implication is that in western countries government should step in to improve citizen response by preparing to facilitate it in times of disaster.
Genetic basis of blood group diversity
Authors: Storry Jill R. , Olsson Martin L. 
Published: October 2004

SummaryIn the last 18 years the genes that encode all but one of the 29 blood group systems present on red blood cells (RBCs) have been identified. This body of knowledge has permitted the application of molecular techniques to characterize the common blood group antigens and to elucidate the background for some of the variant phenotypes. Just as the RBC was used as a model for the biochemical characterization of cell membranes, so the genes encoding blood groups provide a readily accessible model for the study of gene expression and diversity. The application of genotyping techniques to identify fetuses at risk of haemolytic disease of the newborn is now the standard of care, and the expansion of nucleic acid testing platforms to include both disease testing and blood typing in the blood centre is on the horizon. This review summarizes the molecular basis of blood groups and illustrates the mechanisms that generate diversity through specific examples.
The role of PET imaging in lymphoma
Authors: Burton Catherine , Ell Peter , Linch David 
Published: October 2004

SummaryPositron emission tomography using fluorine‐18 (FDG‐PET) is increasingly used in the staging and follow‐up of malignant lymphomas, although its precise role has not yet been determined. This review considers the results reported at the different stages in the disease history and separately considers the major histological subtypes. Attention is given to the situations in which PET scanning is most likely to influence management. Finally, this review discusses ongoing developments in PET scanning with improved resolution and different radiolabelled tracers.
FLT3 mutations in myeloid sarcoma
Authors: Ali Ansari‐Lari M. , Yang Ching‐Fen , Tinawi‐Aljundi Rima , Cooper Lisa , Long Patricia , Allan Robert H. , Borowitz Michael J. , Berg Karin D. , Murphy Kathleen M. 
Published: October 2004

SummaryMyeloid sarcoma is an extramedullary tumour that typically occurs in the setting of acute myeloid leukaemia (AML), or myeloproliferative disorders. In AML, two types of mutations in Fms‐like tyrosine kinase 3 (FLT3) have been described; internal tandem duplications (ITD) and point mutations at aspartic acid residue 835 (D835). We analysed 24 myeloid sarcoma specimens from 20 patients for FLT3 ITD and D835 mutations. FLT3 ITD mutations were identified in three of 20 cases (15%); no D835 mutations were identified. The ITD inserts ranged in size from 33 to 198 base pairs (bp) and represented approximately 20–40% of the FLT3 alleles. Two cases showed discordance in FLT3 ITD mutational status. In one case, the leukaemia specimen was positive for a FLT3 ITD mutation and the myeloid sarcoma specimen was negative. In the second case, the myeloid sarcoma was positive for a FLT3 ITD mutation at diagnosis, but negative in subsequent relapse samples. Our findings suggest that small molecule inhibitors of FLT3 may be useful therapeutic agents for treatment of myeloid sarcomas‐containing FLT3 mutations, however, the potential for discordance between the leukaemia and myeloid sarcoma, necessitates that the myeloid sarcoma tumour itself be analysed for FLT3 mutations.
Dual targeting of Bruton's tyrosine kinase and Janus kinase 3 with rationally designed inhibitors prevents graft‐versus‐host disease (GVHD) in a murine allogeneic bone marrow transplantation model
Authors: Cetkovic‐Cvrlje Marina , Uckun Fatih M. 
Published: October 2004

SummaryThe purpose of the present study was to evaluate the effectiveness of targeting Bruton's tyrosine kinase (BTK) with a specific BTK inhibitor, α‐cyano‐β‐hydroxy‐β‐methyl‐N‐(2,5‐dibromophenyl)‐propenamide (LFM‐A13), for prevention of acute fatal graft‐versus‐host disease (GVHD) in a murine model of allogeneic bone marrow transplantation (BMT). Vehicle‐treated control C57BL/6 mice receiving bone marrow/splenocyte grafts from allogeneic BALB/c donors developed severe multi‐organ acute GVHD and died after a median survival time (MST) of 40 d. LFM‐A13 treatment (25 mg/kg/d) significantly prolonged the MST of the BMT recipients to 47 d. The probability of survival at 2 months after BMT was 2 ± 2% for vehicle‐treated control mice and 22 ± 6% for mice treated with LFM‐A13 (P = 0·0008). Notably, the combination regimen of LFM‐A13 plus the standard anti‐GVHD drug methotrexate (MTX) (10 mg/m2/d) was more effective than LFM‐A13 alone, while the combination regimen of LFM‐A13 plus the novel anti‐GVHD drug JANEX‐1 (60 mg/kg/d), targeting Janus kinase 3, was more effective than LFM‐A13, JANEX‐1 or MTX alone. More than 70% of recipients receiving this most effective GVHD prophylaxis (LFM‐A13 + JANEX‐1) remained alive throughout the 80‐d observation period with an MST of >80 d. Taken together, these results indicate that targeting BTK with the chemical inhibitor LFM‐A13 may attenuate the severity of GVHD, especially when it is combined with other anti‐GVHD drugs, such as MTX and JANEX‐1.
Impaired generation of bone marrow CD34‐derived dendritic cells with low peripheral blood subsets in patients with myelodysplastic syndrome
Authors: Micheva Ilina , Thanopoulou Eleni , Michalopoulou Sotiria , Kakagianni Theodora , Kouraklis‐Symeonidis Alexandra , Symeonidis Argiris , Zoumbos Nicholas 
Published: October 2004

SummaryMyelodysplastic syndrome (MDS) is a stem cell disorder characterized by ineffective haematopoiesis and blood cytopenias. The present study investigated the potential of bone marrow CD34+progenitors in MDS patients to proliferate and differentiate into dendritic cells (DCs) in a cytokine‐supplemented liquid culture system and analysed the status of blood DC subsets in these patients. CD34+progenitors had low potential to generate DCsin vitro, as the number of DCs obtained from one CD34+cell was significantly lower compared with controls (median value 0·2 vs. 4,P = 0·003). In patients, the survival and proliferation of CD34+cells in culture was not correlated to the degree of apoptosis. Phenotypically and functionally CD34+‐derived DCs were similar in MDS patients and normal subjects. The percentage of both circulating DC subsets in patients was extremely diminished compared with controls (myeloid DC: 0·10 ± 0·10% vs. 0·35 ± 0·13%,P < 0·001; plasmacytoid DC: 0·11 ± 0·10% vs. 0·37 ± 0·14%,P < 0·001). In cases with the 5q deletion both CD34‐derived DCs and blood DCs harboured the cytogenetic abnormality. Our results indicate that, in MDS, the production of DCs is affected by the neoplastic process resulting in ineffective ‘dendritopoiesis’ with low blood DC precursor numbers. This quantitative DC defect probably contributes to the poor immune response against infectious agents and to the escape of the malignant clone from immune recognition with disease progression towards acute leukaemia.
Circulating reticulated platelets in the early and late phases after ischaemic stroke and transient ischaemic attack
Authors: McCabe Dominick J. H. , Harrison Paul , Sidhu Paul S. , Brown Martin M. , Machin Samuel J. 
Published: October 2004

SummaryThe percentage of reticulated platelets (% RP) could be a useful marker of increased platelet production and/or turnover in patients with increased platelet activation, but few flow cytometric studies have measured the % RP in patients with ischaemic cerebrovascular disease (CVD). Whole blood flow cytometry using thiazole orange was performed to compare the % RP in patients in the early (1–27 d, n = 79) and late phases (79–725 d, n = 70) after ischaemic stroke or transient ischaemic attack (TIA) with controls without CVD (n = 27). The impact of aspirin dose escalation (75–300 mg/d) on the % RP was investigated in 10 patients in the late phase after stroke/TIA. The platelet count and mean platelet volume (MPV) were similar in CVD patients and controls. Compared with controls, the unadjusted % RP was not significantly higher in early or late phase CVD patients (P ≤ 0·3). However, having adjusted for age, the % RP was higher in early (P = 0·047) and late phase CVD patients (P = 0·01). There was a positive correlation between % RP and MPV in EDTA‐ and citrate‐anticoagulated blood in both early and late phase CVD patients (P≤ 0·01). The % RP was not significantly influenced by aspirin dose. These data do not convincingly support an excessive stimulus to platelet production in the early or late phases after ischaemic stroke/TIA, but are consistent with the hypothesis that reticulated platelets are larger than more mature ‘non‐reticulated’ platelets in ischaemic CVD.
High‐pressure–low‐temperature metamorphism and deformation in the Bündnerschiefer of the Engadine window: implications for the regional evolution of the eastern Central Alps
Authors: BOUSQUET* R. , OBERHÄNSLI R. , GOFFE B. , JOLIVET L. , VIDAL O. 
Published: October 2004

A study of the metamorphic and tectonic evolution of the Bündnerschiefer of the Engadine window shows that the individual nappes have been thinned by a large amount and that extension was active during and soon after nappe stacking.Based on contrasting P–T  histories the Penninic Bündnerschiefer can be divided in two major units bounded by a horizontal contact. The lower (Mundin) unit shows typical high‐P/low‐T  parageneses in metapelites (Mg‐carpholite) and in metabasites (glaucophane); metamorphic conditions are estimated around 12 kbar, 375 °C. The upper (Arina) unit contains no specific high‐P minerals; metamorphic conditions are estimated around 7 kbar, 325 °C. A minimum pressure gap of 5 kbar is thus observed. The contact between the two units is marked by a mappable normal shear zone with top‐to‐the‐north‐west sense of shear. Near the shear zone, fresh carpholite fibres trend parallel to the regional stretching lineation, implying that the detachment is an early structure active from the depth of stability of the carpholite and persisting during subsequent exhumation. The good preservation of carpholite and the absence of retrograde chloritoid below the shear zone show that exhumation occurred along a cooling path, whereas the deeper units are exhumed along an isothermal path. Exhumation probably occurred during convergence and further nappe stacking during the earlier Eocene. These results suggest that pre‐collisional tectonic thinning of the Penninic oceanic units may be more widespread and significant than generally recognized.
Episodic porphyroblast growth in the Fleur de Lys Supergroup, Newfoundland: timing relative to the sequential development of multiple crenulation cleavages
Authors: STALLARD A. 
Published: October 2004

Inclusion trails in garnet and albite porphyroblasts in the Fleur de Lys Supergroup preserve successive generations of microstructures, some of which correlate with equivalent microstructures in the matrix. Microstructure–porphyroblast relationships provide timing constraints on a succession of seven crenulation cleavages (S1–S7) and five stages of porphyroblast growth. Significant destruction and alteration of early fabrics has occurred during the microstructural development of the rock mass. Garnet porphyroblasts grew episodically through four growth stages (G1–G4) and preserve a succession of five fabrics (S1–S5) as inclusion trails. Garnet growth during each of the four growth phases did not occur on all pre‐existing porphyroblasts, resulting in contrasting growth histories between individual garnet porphyroblasts from the same outcrop. Albite porphyroblasts grew during a single stage of growth and have overgrown microstructures continuous with the matrix. The garnet and albite porphyroblast inclusion trails record a succession of crenulation cleavages without any rotation of the porphyroblasts relative to other porphyroblasts in the population.Complex microstructural histories are best resolved by preparing multiple oriented thin sections from a large number of samples of different rock types within the area of study. The succession of matrix foliations must be understood, as it provides the most useful time‐frame against which to measure the relative timing of phases of porphyroblast growth. Comparable microstructures must be identified in different porphyroblasts and in the rock matrix.
Use of Semiconductor Quantum Dots for Photostable Immunofluorescence Labeling of
Cryptosporidium parvum
Authors: Lee Lai Yoke , Ong Say Leong , Hu Jiang Yong , Ng Wun Jern , Feng Yaoyu , Tan Xiaolan , Wong Shih Wei 
Published: October 2004

ABSTRACT

Cryptosporidium parvum
is a waterborne pathogen that poses potential risk to drinking water consumers. The detection of
Cryptosporidium
oocysts, its transmissive stage, is used in the latest U.S. Environmental Protection Agency method 1622, which utilizes organic fluorophores such as fluorescein isothiocyanate (FITC) to label the oocysts by conjugation with anti-
Cryptosporidium
sp. monoclonal antibody (MAb). However, FITC exhibits low resistance to photodegradation. This property will inevitably limit the detection accuracy after a short period of continuous illumination. In view of this, the use of inorganic fluorophores, such as quantum dot (QD), which has a high photobleaching threshold, in place of the organic fluorophores could potentially enhance oocyst detection. In this study, QD605-streptavidin together with biotinylated MAb was used for
C. parvum
oocyst detection. The
C. parvum
oocyst detection sensitivity increased when the QD605-streptavidin concentration was increased from 5 to 15 nM and eventually leveled off at a saturation concentration of 20 nM and above. The minimum QD605-streptavidin saturation concentration for detecting up to 4,495 ± 501 oocysts (mean ± standard deviation) was determined to be 20 nM. The difference in the enumeration between 20 nM QD605-streptavidin with biotinylated MAb and FITC-MAb was insignificant (
P
> 0.126) when various
C. parvum
oocyst concentrations were used. The QD605 was highly photostable while the FITC intensity decreased to 19.5% ± 5.6% of its initial intensity after 5 min of continuous illumination. The QD605-based technique was also shown to be sensitive for oocyst detection in reservoir water. This observation showed that the QD method developed in this study was able to provide a sensitive technique for detecting
C. parvum
oocysts with the advantage of having a high photobleaching threshold.
Distribution of
Escherichia coli
O157 in Bovine Fecal Pats and Its Impact on Estimates of the Prevalence of Fecal Shedding
Authors: Pearce M. C. , Fenlon D. , Low J. C. , Smith A. W. , Knight H. I. , Evans J. , Foster G. , Synge B. A. , Gunn G. J. 
Published: October 2004

ABSTRACT

The distribution of
Escherichia coli
O157 in bovine feces was examined by testing multiple samples from fecal pats and determining the density of
E. coli
O157 in immunomagnetic separation (IMS)-positive fecal samples. The density of
E. coli
O157 in bovine feces was highly variable, differing by as much as 76,800 CFU g
−1
between samples from the same fecal pat. The density in most positive samples was <100 CFU g
−1
, the limit of reliable detection by IMS. Testing only one 1-g sample of feces per pat with IMS may result in a sensitivity of detection as low as 20 to 50%. It is therefore probable that most surveys have greatly underestimated the prevalence of
E. coli
O157 shedding in cattle and the proportion of farms with shedding cattle. The sensitivity of the detection of
E. coli
O157 in bovine feces can be as much as doubled by testing two 1-g samples per pat rather than one 1-g sample.
Mechanisms of Bactericidal Action of Cinnamaldehyde against
Listeria monocytogenes
and of Eugenol against
L. monocytogenes
and
Lactobacillus sakei
Authors: Gill Alexander O. , Holley Richard A. 
Published: October 2004

ABSTRACT

The spice oil components eugenol and cinnamaldehyde possess activity against both gram-positive and gram-negative bacteria, but the mechanisms of action remain obscure. In broth media at 20°C, 5 mM eugenol or 30 mM cinnamaldehyde was bactericidal (>1-log reduction in the number of CFU per milliliter in 1 h) to
Listeria monocytogenes
. At a concentration of 6 mM eugenol was bactericidal to
Lactobacillus sakei
, but treatment with 0.5 M cinnamaldehyde had no significant effect. To investigate the role of interference with energy generation in the mechanism of action, the cellular and extracellular ATP levels of cells in HEPES buffer at 20°C were measured. Treatment of nonenergized
L. monocytogenes
with 5 mM eugenol, 40 mM cinnamaldehyde, or 10 μM carbonyl cyanide
m
-chlorophenylhydrazone (CCCP) for 5 min prevented an increase in the cellular ATP concentration upon addition of glucose. Treatment of energized
L. monocytogenes
with 40 mM cinnamaldehyde or 10 μM CCCP caused a rapid decline in cellular ATP levels, but 5 mM eugenol had no effect on cellular ATP. Treatment of
L. sakei
with 10 mM eugenol prevented ATP generation by nonenergized cells and had no effect on the cellular ATP of energized cells. CCCP at a concentration of 100 μM had no significant effect on the cellular ATP of
L. sakei
. No significant changes in extracellular ATP were observed. Due to their rapidity, effects on energy generation clearly play a major role in the activity of eugenol and cinnamaldehyde at bactericidal concentrations. The possible mechanisms of inhibition of energy generation are inhibition of glucose uptake or utilization of glucose and effects on membrane permeability.