bluuebunny/crossref_metadata_2025 huggingface dataset:
Holistic Home Hospice: Caring for a Dying Father—A Family Hermeneutic Exemplar
Authors: Callahan Rita R.
Published: July 2005

This exemplar focuses on the patient and the family. The challenges of caring for a dying parent are numerous, but having the resourcefulness of home hospice may assist in such a struggle. The home hospice experience involves providing care while attending to the sensitivity needs of culture, religion, and emotions. Many share a lack of knowledge regarding available in-home services such as home hospice, which allows one the independent opportunity to die with dignity in the comfort of one’s own environment with a sense of peace, familiarity, and familial love. While the family cared for their dying father, little did they know that actual caring would require a holistic approach and that an out-of-home agency was available to guide them through what would become an unfortunate experience, yet a successful one.
Elimination of human leukemia cells in NOD/SCID mice by WT1-TCR gene–transduced human T cells
Authors: Xue Shao-An , Gao Liquan , Hart Daniel , Gillmore Roopinder , Qasim Waseem , Thrasher Adrian , Apperley Jane , Engels Boris , Uckert Wolfgang , Morris Emma , Stauss Hans
Published: July 2005

Cytotoxic T lymphocytes (CTLs) specific for an HLA-A2–presented peptide epitope of the Wilms tumor antigen-1 (WT1) can selectively kill immature human leukemia progenitor and stem cells in vitro. In this study we have used retroviral gene transfer to introduce a WT1-specific T-cell receptor (TCR) into T lymphocytes obtained from patients with leukemia and from healthy donors. TCR-transduced T cells kill leukemia cells in vitro and display WT1-specific cytokine production. Intravenous injection of TCR-transduced T cells into nonobese diabetic–severe combined immunodeficiency (NOD/SCID) mice harboring human leukemia cells resulted in leukemia elimination, whereas transfer of control T cells transduced with an irrelevant TCR was ineffective. The data suggest that adoptive immunotherapy with WT1-TCR gene–modified patient T cells should be considered for the treatment of leukemia.
Mitochondrial DNA spectra of single human CD34+ cells, T cells, B cells, and granulocytes
Authors: Ogasawara Yoji , Nakayama Kazutaka , Tarnowka Magdalena , McCoy J. Philip , Kajigaya Sachiko , Levin Barbara C. , Young Neal S.
Published: July 2005

Previously, we described the age-dependent accumulation of mitochondrial DNA (mtDNA) mutations, leading to a high degree of mtDNA heterogeneity among normal marrow and blood CD34+ clones and in granulocytes. We established a method for sequence analysis of single cells. We show marked, distinct mtDNA heterogeneity from corresponding aggregate sequences in isolated cells of 5 healthy adult donors—37.9% ± 3.6% heterogeneity in circulating CD34+ cells, 36.4% ± 14.1% in T cells, 36.0% ± 10.7% in B cells, and 47.7% ± 7.4% in granulocytes. Most heterogeneity was caused by poly-C tract variability; however, base substitutions were also prevalent, as follows: 14.7% ± 5.7% in CD34+ cells, 15.2% ± 9.0% in T cells, 15.4% ± 6.7% in B cells, and 32.3% ± 2.4% in granulocytes. Many poly-C tract length differences and specific point mutations seen in these same donors but assayed 2 years earlier were still present in the new CD34+ samples. Additionally, specific poly-C tract differences and point mutations were frequently shared among cells of the lymphoid and myeloid lineages. Secular stability and lineage sharing of mtDNA sequence variability suggest that mutations arise in the lymphohematopoietic stem cell compartment and that these changes may be used as a natural genetic marker to estimate the number of active stem cells.
Intracellular labile iron pools as direct targets of iron chelators: a fluorescence study of chelator action in living cells
Authors: Glickstein Hava , Ben El Rinat , Shvartsman Maya , Cabantchik Z. Ioav
Published: July 2005

The primary targets of iron chelators used for treating transfusional iron overload are prevention of iron ingress into tissues and its intracellular scavenging. The present study was aimed at elucidating the capacity of clinically important iron chelators such as deferiprone (DFP), desferrioxamine, and ICL670 to (a) gain direct access to intracellular iron pools of key cells of iron accumulation (macrophages, hepatocytes, and cardiomyocyte cell lines); (b) chelate the labile iron present in discrete cell compartments/organelles; and (c) prevent labile iron involvement in the generation of reactive oxidant species. Chelation of cytosolic and organellar cell iron was visualized dynamically and quantitatively in living cells by fluorescence microscopic imaging of fluorescent metallosensors (used as iron-quenched complexes of calceins) targeted to either cytosol, endosome-lysosomes, or mitochondria. The rate and extent of fluorescence recovery provided an in situ measure of the accessibility of chelators to particular cell sites/organelles. Complementary, fluorogenic redox probes associated with cell compartments enabled identification of chelator-sensitive, localized reactive oxidant production. Our studies indicate that chelation by desferrioxamine is slow and is enhanced in cells with relatively high endocytic activities, while ICL670 and DFP readily enter most cells and efficiently reach the major intracellular sites of iron accumulation.
Three pathways to mature macrophages in the early mouse yolk sac
Authors: Bertrand Julien Y. , Jalil Abdelali , Klaine Michèle , Jung Steffen , Cumano Ana , Godin Isabelle
Published: July 2005

The existence of macrophages (Mφ) of yolk-sac (YS) origin has been reported in all vertebrate models. However, the nature of their precursors and pathways of differentiation have not been elucidated. Phenotypic and differentiation potential analyses of YS at 7.5 to 10 postcoital days (dpc), performed in CX3CR1GFP embryos, allowed us to discern 3 independent Mφ populations. A first transient wave consisted of mature, maternal-derived Mφpresent as early as 7.5 to 8 dpc. A second wave of committed Mφ precursors arose at 8 dpc (2-4 somite stage) and was followed by a third wave of erythromyeloid precursors (4-6 somite stage). Both types of precursors displayed similar phenotypes and gave rise to CX3CR1/green fluorescent protein (GFP)–positive Mφ, but differed by their differentiation potential, at the clonal level. The combined data of phenotypic, gene-expression, and in situ analyses allowed us to conclude that the previously named “primitive Mφ” corresponded to a mixture of the first transient wave and committed Mφ precursors. Both YS-derived precursors followed a developmental pathway common to adult Mφ and could be qualified as definitive.
LPS induces CD40 gene expression through the activation of NF-κB and STAT-1α in macrophages and microglia
Authors: Qin Hongwei , Wilson Cynthia A. , Lee Sun Jung , Zhao Xueyan , Benveniste Etty N.
Published: July 2005

CD40 is expressed on various immune cells, including macrophages and microglia. Aberrant expression of CD40 is associated with autoimmune inflammatory diseases such as multiple sclerosis and rheumatoid arthritis. Interaction of Toll-like receptor-4 (TLR4) with the Gram-negative bacteria endotoxin lipopolysaccharide (LPS) results in the induction of an array of immune response genes. In this study, we describe that LPS is a strong inducer of CD40 expression in macrophages and microglia, which occurs at the transcriptional level and involves the activation of the transcription factors nuclear factor-κB (NF-κB) and signal transducer and activator of transcription 1α (STAT-1α). LPS-induced CD40 expression involves the endogenous production of the cytokine interferon-beta (IFN-β), which contributes to CD40 expression by the activation of STAT-1α. Blocking IFN-β–induced activation of STAT-1α by IFN-β–neutralizing antibody reduces LPS-induced CD40 gene expression. Furthermore, LPS induces acetylation and phosphorylation of histones H3 and H4 and the recruitment of NF-κB, STAT-1α, and RNA polymerase II on the CD40 promoter in vivo in a time-dependent manner, all events important for CD40 gene transcription. These results indicate that both LPS-induced NF-κB activation and endogenous production of IFN-β that subsequently induces STAT-1α activation play critical roles in the transcriptional activation of the CD40 gene by LPS.
Jak3 negatively regulates dendritic-cell cytokine production and survival
Authors: Yamaoka Kunihiro , Min Booki , Zhou Yong-Jie , Paul William E. , O'Shea John J.
Published: July 2005

Cytokines are critical in regulating the development and function of diverse cells. Janus kinase 3 (Jak3) is a tyrosine kinase expressed in hematopoietic cells that associates with the common gamma chain (γc) and is required for signaling for a family of cytokines including interleukin-2 (IL-2), IL-4, IL-7, IL-9, IL-15, and IL-21; deficiency of either Jak3 or γc results in severe combined immunodeficiency (SCID). While Jak3 is essential for lymphoid-cell development, the potential roles for Jak3 in regulating dendritic cells (DCs) were unclear. Herein, we show that although CD8+CD11c+ splenic DCs are absent in Jak3-/- mice, bone marrow–derived DCs developed normally in vitro from Jak3-/- precursor cells. In fact, the survival of Jak3-/- DCs was enhanced, and they expressed lower levels of proapoptotic proteins. Jak3-/- DCs exhibited normal antigen uptake and up-regulation of costimulatory molecules. However, Jak3-/- DCs produced more IL-12 and IL-10 in response to Toll-like receptor ligands, which correlated with enhanced T helper 1 (Th1) differentiation in vivo. In summary, Jak3 is not essential for DC development but unexpectedly appears to be an important negative regulator. These results may be relevant clinically for patients with SCID who have undergone hematopoietic stem cell transplantation and for patients who might be treated with a Jak3 inhibitor.
Tumor necrosis factor-α inhibits hTERT gene expression in human myeloid normal and leukemic cells
Authors: Beyne-Rauzy Odile , Prade-Houdellier Naïs , Demur Cécile , Recher Christian , Ayel Jacques , Laurent Guy , Mansat-De Mas Véronique
Published: July 2005

Telomerase catalytic subunit (hTERT) has been shown to play a critical role not only in telomere homeostasis but also in cellular survival, DNA repair, and genetic stability. In a previous study, we described that tumor necrosis factor-×α (TNF×α) induced in the leukemic KG1 cells a senescence state characterized by decreased hTERT activity followed by prolonged growth arrest, increased× β-galactosidase activity, telomere shortening, and major chromosomal instability. Interestingly, granulocyte-macrophage colony-stimulating factor (GM-CSF) abrogated all these events. In the present study, we show for the first time that TNF×α acts by inhibiting the hTERT gene in both normal CD34×+ cells and fresh leukemic cells. Using KG1 cells as a representative cellular model, we show that TNF×α induced sphingomyelin hydrolysis, ceramide production, and c-Jun N-terminal kinase (JNK) activation, all of which are critical components of TNF×α signaling, resulting in hTERT gene inhibition. Moreover, we provide evidence that the protective effect of GM-CSF is related to its capacity to interfere with both ceramide generation and ceramide signaling. Negative regulation of the hTERT gene may represent one mechanism by which TNF×α interferes with normal hemopoiesis.
Src family kinase–mediated and Erk-mediated thromboxane A2 generation are essential for VWF/GPIb-induced fibrinogen receptor activation in human platelets
Authors: Garcia Analia , Quinton Todd M. , Dorsam Robert T. , Kunapuli Satya P.
Published: July 2005

The binding of von Willebrand factor (VWF) to the platelet membrane glycoprotein Ib-IX (GPIb-IX) results in platelet activation. In this study, we sought to clarify previous conflicting reports and to elucidate the mechanism of activation and the precise role of extracellular signal-regulated kinase (Erk) in VWF-induced platelet activation. Erk2 is activated in platelets on stimulation with VWF/ristocetin in a time-dependent manner. VWF-induced Erk2 phosphorylation and thromboxane A2 (TXA2) release were completely blocked by PP2, an Src family kinase inhibitor, suggesting that Erk is downstream of Src family kinases. U73122, a phospholipase C inhibitor, also abolished TXA2 generation and Erk phosphorylation. Although VWF fostered the agglutination of platelets regardless of any additional treatment, the inhibition of mitogen-activated protein kinase kinase (MEK) with U0126 abolished VWF-induced platelet aggregation and thromboxane production in non–aspirin-treated washed platelets. However, in platelets treated with aspirin, VWF failed to cause any aggregation. Thus, we conclude that VWF stimulation of platelets results in phospholipase A2 activation through Erk stimulation and that Src family kinases and phospholipase C play essential roles in this event. We further conclude that VWF-induced platelet aggregation does not directly depend on Erk activation but has an absolute requirement for Src/Erk-mediated TXA2 generation.
Successful treatment of Erdheim-Chester disease, a non–Langerhans-cell histiocytosis, with interferon-α
Authors: Braiteh Fadi , Boxrud Cynthia , Esmaeli Bita , Kurzrock Razelle
Published: July 2005

Erdheim-Chester disease is a rare non-Langerhans histiocytosis with multisystem involvement. To date, there is no standard treatment for this disorder, and more than half of the patients succumb within 3 years. Because interferon-α promotes the terminal differentiation of histiocytes and dendritic cells, we hypothesized that this molecule would be a useful therapy for Erdheim-Chester disease. We therefore treated 3 patients with advanced disease with interferon-α at a starting dose of 3 to 6 × 106 units, which was later reduced, during maintenance, to 1 × 106 units subcutaneous 3 times per week. Marked improvement was noted in all patients, with substantial retro-orbital disease regression within 1 month. Improvement in bone lesions, pain, diabetes insipidus, and other manifestations was gradual over many months. Responses were durable (3+ to 4.5+ years). Our observations suggest that this well-tolerated therapy has a significant effect on the course and outcome of Erdheim-Chester disease.
Characterization of 17α-hydroxysteroid dehydrogenase activity (17α-HSD) and its involvement in the biosynthesis of epitestosterone
Authors: Bellemare Véronique , Faucher Frédérick , Breton Rock , Luu-The Van
Published: July 2005

Background

Epi-testosterone (epiT) is the 17α-epimer of testosterone. It has been found at similar level as testosterone in human biological fluids. This steroid has thus been used as a natural internal standard for assessing testosterone abuse in sports. EpiT has been also shown to accumulate in mammary cyst fluid and in human prostate. It was found to possess antiandrogenic activity as well as neuroprotective effects. So far, the exact pathway leading to the formation of epiT has not been elucidated.

Results

In this report, we describe the isolation and characterization of the enzyme 17α-hydroxysteroid dehydrogenase. The name is given according to its most potent activity. Using cells stably expressing the enzyme, we show that 17α-HSD catalyzes efficienty the transformation of 4-androstenedione (4-dione), dehydroepiandrosterone (DHEA), 5α-androstane-3,17-dione (5α-dione) and androsterone (ADT) into their corresponding 17α-hydroxy-steroids : epiT, 5-androstene-3β,17α-diol (epi5diol), 5α-androstane-17α-ol-3-one (epiDHT) and 5α-androstane-3α,17α-diol (epi3α-diol), respectively. Similar to other members of the aldo-keto reductase family that possess the ability to reduce the keto-group into hydroxyl-group at different position on the steroid nucleus, 17α-HSD could also catalyze the transformation of DHT, 5α-dione, and 5α-pregnane-3,20-dione (DHP) into 3α-diol, ADT and 5α-pregnane-3α-ol-20-one (allopregnanolone) through its less potent 3α-HSD activity. We also have over-expressed the 17α-HSD in Escherichia coli and have purified it by affinity chromatography. The purified enzyme exhibits the same catalytic properties that have been observed with cultured HEK-293 stably transfected cells. Using quantitative Realtime-PCR to study tissue distribution of this enzyme in the mouse, we observed that it is expressed at very high levels in the kidney.

Conclusion

The present study permits to clarify the biosynthesis pathway of epiT. It also offers the opportunity to study gene regulation and function of this enzyme. Further study in human will allow a better comprehension about the use of epiT in drug abuse testing; it will also help to clarify the importance of its accumulation in breast cyst fluid and prostate, as well as its potential role as natural antiandrogen.
Dissecting systems-wide data using mixture models: application to identify affected cellular processes
Authors: Svensson J Peter , de Menezes Renée X , Turesson Ingela , Giphart-Gassler Micheline , Vrieling Harry
Published: July 2005

Background

Functional analysis of data from genome-scale experiments, such as microarrays, requires an extensive selection of differentially expressed genes. Under many conditions, the proportion of differentially expressed genes is considerable, making the selection criteria a balance between the inclusion of false positives and the exclusion of false negatives.

Results

We developed an analytical method to determine a p-value threshold from a microarray experiment that is dependent on the quality and design of the data set. To this aim, populations of p-values are modeled as mathematical functions in which the parameters to describe these functions are estimated in an unsupervised manner. The strength of the method is exemplified by its application to a published gene expression data set of sporadic and familial breast tumors with BRCA1 or BRCA2 mutations.

Conclusion

We present an objective and unsupervised way to set thresholds adapted to the quality and design of the experiment. The resulting mathematical description of the data sets of genome-scale experiments enables a probabilistic approach in systems biology.
The recombination activation gene 1 (Rag1) is expressed in a subset of zebrafish olfactory neurons but is not essential for axon targeting or amino acid detection
Authors: Feng Bo , Bulchand Sarada , Yaksi Emre , Friedrich Rainer W , Jesuthasan Suresh
Published: July 2005

Background

Rag1 (Recombination activation gene-1) mediates genomic rearrangement and is essential for adaptive immunity in vertebrates. This gene is also expressed in the olfactory epithelium, but its function there is unknown.

Results

Using a transgenic zebrafish line and immunofluorescence, we show that Rag1 is expressed and translated in a subset of olfactory sensory neurons (OSNs). Neurons expressing GFP under the Rag1 promoter project their axons to the lateral region of the olfactory bulb only, and axons with the highest levels of GFP terminate in a single glomerular structure. A subset of GFP-expressing neurons contain Gαo, a marker for microvillous neurons. None of the GFP-positive neurons express Gαolf, Gαq or the olfactory marker protein OMP. Depletion of RAG1, by morpholino-mediated knockdown or mutation, did not affect axon targeting. Calcium imaging indicates that amino acids evoke chemotopically organized glomerular activity patterns in a Rag1 mutant.

Conclusion

Rag1 expression is restricted to a subpopulation of zebrafish olfactory neurons projecting to the lateral olfactory bulb. RAG1 catalytic activity is not essential for axon targeting, nor is it likely to be required for regulation of odorant receptor expression or the response of OSNs to amino acids.
Pragmatic application of a clinical prediction rule in primary care to identify patients with low back pain with a good prognosis following a brief spinal manipulation intervention
Authors: Fritz Julie M , Childs John D , Flynn Timothy W
Published: July 2005

Background

Patients with low back pain are frequently encountered in primary care. Although a specific diagnosis cannot be made for most patients, it is likely that sub-groups exist within the larger entity of nonspecific low back pain. One sub-group that has been identified is patients who respond rapidly to spinal manipulation. The purpose of this study was to examine the association between two factors (duration and distribution of symptoms) and prognosis following a spinal manipulation intervention.

Methods

Data were taken from two previously published studies. Patients with low back pain underwent a standardized examination, including assessment of duration of the current symptoms in days, and the distal-most distribution of symptoms. Based on prior research, patients with symptoms of <16 days duration and no symptoms distal to the knee were considered to have a good prognosis following manipulation. All patients underwent up to two sessions of spinal manipulation treatment and a range of motion exercise. Oswestry disability scores were recorded before and after treatment. If ≥ 50% improvement on the Oswestry was achieved, the intervention was considered a success. Sensitivity, specificity, and positive likelihood ratio were calculated for the association of the two criteria with the outcome of the treatment.

Results

141 patients (49% female, mean age = 35.5 (± 11.1) years) participated. Mean pre- and post-treatment Oswestry scores were 41.9 (± 10.9) and 24.1 (± 14.2) respectively. Sixty-three subjects (45%) had successful treatment outcomes. The sensitivity of the two criteria was 0.56 (95% CI: 0.43, 0.67), specificity was 0.92 (95% CI: 0.84, 0.96), and the positive likelihood ratio was 7.2 (95% CI: 3.2, 16.1).

Conclusion

The results of this study demonstrate that two factors; symptom duration of less than 16 days, and no symptoms extending distal to the knee, were associated with a good outcome with spinal manipulation.
Comparative evaluation of efficacy and safety of ophthalmic viscosurgical devices in phacoemulsification [ISRCTN34957881]
Authors: Vajpayee Rasik B , Verma Kamna , Sinha Rajesh , Titiyal Jeewan S , Pandey RM , Sharma Namrata
Published: July 2005

Background

Various ophthalmic viscosurgical devices (OVD) are used to perform phacoemulsification and other intraocular surgeries. We performed a study to compare the efficacy and safety of three ophthalmic viscosurgical devices that are routinely used in phacoemulsification.

Methods

Fifty-six patients of immature senile cataract with hard nucleus (grade 3 and 4) who underwent phacoemulsification were included. Depending upon the type of OVD, patients were randomly allocated into three groups; group 1 (n = 19), Viscoat® was used; group 2 (n = 19), Healon GV® was used; group 3 (n = 18), Healon 5® was used. Parameters evaluated were uncorrected and best corrected visual acuity, specular microscopy, intraocular pressure and pachymetry both preoperatively and postoperatively on day 1, 1 week, 1 month and 3 months and development of any complication both intraoperative and postoperative were also noted.

Results

The mean increase in central corneal thickness was 15.17% (group 1); 17.26% (group 2) and 16.21% (group 3) on first postoperative day and was comparable in the three groups. The density of endothelial cells decreased postoperatively (day 1) by 12.54% (group 1), 13.76% (group 2) and 13.06% (group 3) and was comparable. The mean preoperative intraocular pressure in groups 1, 2 and 3 were 13.3 ± 2.0, 14.0 ± 2.2 and 13.2 ± 3.2 mmHg respectively, which changed to 16.0 ± 4.7, 12.2 ± 4.7 and 12.3 ± 4.8 respectively on first postoperative day and the change in intraocular pressure was significantly higher in group 1 (1 vs 2 & 1 vs 3; p = 0.02; oneway ANOVA).

Conclusion

Viscoat®, Healon GV® and Healon 5® give comparable results in terms of efficacy and safety in performing phacoemulsification.
Are alcoholism treatments effective? The Project MATCH data
Authors: Cutler Robert B , Fishbain David A
Published: July 2005

Background

Project MATCH was the largest and most expensive alcoholism treatment trial ever conducted. The results were disappointing. There were essentially no patient-treatment matches, and three very different treatments produced nearly identical outcomes. These results were interpreted post hoc as evidence that all three treatments were quite effective. We re-analyzed the data in order to estimate effectiveness in relation to quantity of treatment.

Methods

This was a secondary analysis of data from a multisite clinical trial of alcohol dependent volunteers (N = 1726) who received outpatient psychosocial therapy. Analyses were confined to the primary outcome variables, percent days abstinent (PDA) and drinks per drinking day (DDD). Overall tests between treatment outcome and treatment quantity were conducted. Next, three specific groups were highlighted. One group consisted of those who dropped out immediately; the second were those who dropped out after receiving only one therapy session, and the third were those who attended 12 therapy sessions.

Results

Overall, a median of only 3% of the drinking outcome at follow-up could be attributed to treatment. However this effect appeared to be present at week one before most of the treatment had been delivered. The zero treatment dropout group showed great improvement, achieving a mean of 72 percent days abstinent at follow-up. Effect size estimates showed that two-thirds to three-fourths of the improvement in the full treatment group was duplicated in the zero treatment group. Outcomes for the one session treatment group were worse than for the zero treatment group, suggesting a patient self selection effect. Nearly all the improvement in all groups had occurred by week one. The full treatment group had improved in PDA by 62% at week one, and the additional 11 therapy sessions added only another 4% improvement.

Conclusion

The results suggest that current psychosocial treatments for alcoholism are not particularly effective. Untreated alcoholics in clinical trials show significant improvement. Most of the improvement which is interpreted as treatment effect is not due to treatment. Part of the remainder appears to be due to selection effects.
Metabolic adaptations to repeated periods of contraction with reduced blood flow in canine skeletal muscle
Authors: MacInnes Alan , Timmons James A
Published: July 2005

Background

Patients suffering from Intermittent Claudication (IC) experience repeated periods of muscle contraction with low blood flow, throughout the day and this may contribute to the hypothesised skeletal muscle abnormalities. However, no study has evaluated the consequences of intermittent contraction with low blood flow on skeletal muscle tissue. Our aim was to generate this basic physiological data, determining the 'normal' response of healthy skeletal muscle tissue. We specifically proposed that the metabolic responses to contraction would be modified under such circumstances, revealing endogenous strategies engaged to protect the muscle adenine nucleotide pool. Utilizing a canine gracilis model (n = 9), the muscle was stimulated to contract (5 Hz) for three 10 min periods (separated by 10 min rest) under low blood flow conditions (80% reduced), followed by 1 hr recovery and then a fourth period of 10 min stimulation. Muscle biopsies were obtained prior to and following the first and fourth contraction periods. Direct arterio-venous sampling allowed for the calculation of muscle metabolite efflux and oxygen consumption.

Results

During the first period of contraction, [ATP] was reduced by ~30%. During this period there was also a 10 fold increase in muscle lactate concentration and a substantial increase in muscle lactate and ammonia efflux. Subsequently, lactate efflux was similar during the first three periods, while ammonia efflux was reduced by the third period. Following 1 hr recovery, muscle lactate and phosphocreatine concentrations had returned to resting values, while muscle [ATP] remained 20% lower. During the fourth contraction period no ammonia efflux or change in muscle ATP content occured. Despite such contrasting metabolic responses, muscle tension and oxygen consumption were identical during all contraction periods from 3 to 10 min.

Conclusion

repeated periods of muscle contraction, with low blood flow, results in cessation of muscle ammonia production which is suggestive of a dramatic reduction in flux through AMP deaminase.
Id4 and FABP7 are preferentially expressed in cells with astrocytic features in oligodendrogliomas and oligoastrocytomas
Authors: Liang Yu , Bollen Andrew W , Nicholas M Kelly , Gupta Nalin
Published: July 2005

Background

Oligodendroglioma (ODG) and oligoastrocytoma (OAC) are diffusely infiltrating primary brain tumors whose pathogenesis remains unclear. We previously identified a group of genes whose expression was inversely correlated with survival in a cohort of patients with glioblastoma (GBM), and some of these genes are also reportedly expressed in ODG and OAC. We examined the expression patterns and localization of these survival-associated genes in ODG and OAC in order to analyze their possible roles in the oncogenesis of these two tumor types.

Methods

We used UniGene libraries derived from GBM and ODG specimens to examine the expression levels of the transcripts for each of the 50 GBM survival-associated genes. We used immunohistochemistry and cDNA microarrays to examine expression of selected survival-associated genes and Id4, a gene believed to control the timing of oligodendrocyte development. The expression of FABP7 and Id4 and the survival of patients with ODG and OAC were also analyzed.

Results

Transcripts of most survival-associated genes as well as Id4 were present in both GBM and ODG tumors, whereas protein expression of Id4 and one of the survival-associated genes, brain-type fatty acid-binding protein (FABP7), was present in cells with astrocytic features, including reactive and neoplastic astrocytes, but not in neoplastic oligodendrocytes. Id4 was co-expressed with FABP7 in microgemistocytes in ODG and in neoplastic astrocytes in OAC. Id4 and FABP7 expression, however, did not correlate with the clinical outcome of patients with ODG or OAC tumors.

Conclusion

Expression of Id4 and some of our previously identified GBM survival-associated genes is present in developing or mature oligodendrocytes. However, protein expression of Id4 and FABP7 in GBM, ODG, and OAC suggests that this group of functionally important genes might demonstrate two patterns of expression in these glioma subtypes: one group is universally expressed in glioma cells, and the other group of genes is expressed primarily in neoplastic astrocytes but not in neoplastic oligodendrocytes. Differential protein expression of these two groups of genes in ODG and OAC may be related to the cellular origins and the histological features of the neoplastic cells.
The pioneer cohort of curriculum reform: Guinea pigs or trail-blazers?
Authors: McLean Michelle
Published: July 2005

With curriculum reform, whether we admit it or not, the first cohort of students will be 'test-driving' the new programme. Not only are they the pioneers of a new curriculum, but as they progress through their studies, they experience each year of the innovation for the first time. As curriculum designers, we learn from their experiences and their feedback to improve the programme content and delivery, invariably for subsequent cohorts. A considerable onus therefore rests with this pioneer group, and their contribution to curriculum design, evaluation and programme revision should be valued.
A software tool for creating simulated outbreaks to benchmark surveillance systems
Authors: Cassa Christopher A , Iancu Karin , Olson Karen L , Mandl Kenneth D
Published: July 2005

Background

Evaluating surveillance systems for the early detection of bioterrorism is particularly challenging when systems are designed to detect events for which there are few or no historical examples. One approach to benchmarking outbreak detection performance is to create semi-synthetic datasets containing authentic baseline patient data (noise) and injected artificial patient clusters, as signal.

Methods

We describe a software tool, the AEGIS Cluster Creation Tool (AEGIS-CCT), that enables users to create simulated clusters with controlled feature sets, varying the desired cluster radius, density, distance, relative location from a reference point, and temporal epidemiological growth pattern. AEGIS-CCT does not require the use of an external geographical information system program for cluster creation. The cluster creation tool is an open source program, implemented in Java and is freely available under the Lesser GNU Public License at its Sourceforge website. Cluster data are written to files or can be appended to existing files so that the resulting file will include both existing baseline and artificially added cases. Multiple cluster file creation is an automated process in which multiple cluster files are created by varying a single parameter within a user-specified range. To evaluate the output of this software tool, sets of test clusters were created and graphically rendered.

Results

Based on user-specified parameters describing the location, properties, and temporal pattern of simulated clusters, AEGIS-CCT created clusters accurately and uniformly.

Conclusion

AEGIS-CCT enables the ready creation of datasets for benchmarking outbreak detection systems. It may be useful for automating the testing and validation of spatial and temporal cluster detection algorithms.
Automatic control of finite element models for temperature-controlled radiofrequency ablation
Authors: Haemmerich Dieter , Webster John G
Published: July 2005

Background

The finite element method (FEM) has been used to simulate cardiac and hepatic radiofrequency (RF) ablation. The FEM allows modeling of complex geometries that cannot be solved by analytical methods or finite difference models. In both hepatic and cardiac RF ablation a common control mode is temperature-controlled mode. Commercial FEM packages don't support automating temperature control. Most researchers manually control the applied power by trial and error to keep the tip temperature of the electrodes constant.

Methods

We implemented a PI controller in a control program written in C++. The program checks the tip temperature after each step and controls the applied voltage to keep temperature constant. We created a closed loop system consisting of a FEM model and the software controlling the applied voltage. The control parameters for the controller were optimized using a closed loop system simulation.

Results

We present results of a temperature controlled 3-D FEM model of a RITA model 30 electrode. The control software effectively controlled applied voltage in the FEM model to obtain, and keep electrodes at target temperature of 100°C. The closed loop system simulation output closely correlated with the FEM model, and allowed us to optimize control parameters.

Discussion

The closed loop control of the FEM model allowed us to implement temperature controlled RF ablation with minimal user input.
Detection of trypanosomes in small ruminants and pigs in western Kenya: important reservoirs in the epidemiology of sleeping sickness?
Authors: Ng'ayo Musa O , Njiru Zablon K , Kenya Eucharia U , Muluvi Geoffrey M , Osir Ellie O , Masiga Daniel K
Published: July 2005

Background

Trypanosomosis is a major impediment to livestock farming in sub-Saharan Africa and limits the full potential of agricultural development in the 36 countries where it is endemic. In man, sleeping sickness is fatal if untreated and causes severe morbidity. This study was undertaken in western Kenya, an area that is endemic for both human and livestock trypanosomosis. While trypanosomosis in livestock is present at high levels of endemicity, sleeping sickness occurs at low levels over long periods, interspersed with epidemics, underscoring the complexity of the disease epidemiology. In this study, we sought to investigate the prevalence of trypanosomes in small ruminants and pigs, and the potential of these livestock as reservoirs of potentially human-infective trypanosomes. The study was undertaken in 5 villages, to address two key questions: i) are small ruminants and pigs important in the transmission dynamics of trypanosomosis? and ii), do they harbour potentially human infective trypanosomes? Answers to these questions are important in developing strategies for the control of both livestock and human trypanosomosis.

Results

Eighty-six animals, representing 21.3% of the 402 sampled in the 5 villages, were detected as positive by PCR using a panel of primers that identify trypanosomes to the level of the species and sub-species. These were categorised as 23 (5.7%) infections of T. vivax, 22 (5.5%) of T. simiae, 21 (5.2%) of the T. congolense clade and 20 (5.0%) of T. brucei ssp. The sheep was more susceptible to trypanosome infection as compared to goats and pigs. The 20 T. brucei positive samples were evaluated by PCR for the presence of the Serum Resistance Associated (SRA) gene, which has been linked to human infectivity in T. b. rhodesiense. Three samples (one pig, one sheep and one goat) were found to have the SRA gene. These results suggest that sheep, goats and pigs, which are kept alongside cattle, may harbour human-infective trypanosomes.

Conclusion

We conclude that all livestock kept in this T. b. rhodesiense endemic area acquire natural infections of trypanosomes, and are therefore important in the transmission cycle. Sheep, goats and pigs harbour trypanosomes that are potentially infective to man. Hence, the control of trypanosomosis in these livestock is essential to the success of any strategy to control the disease in man and livestock.
A retrospective study of PBDEs and PCBs in human milk from the Faroe Islands
Authors: Fängström Britta , Strid Anna , Grandjean Philippe , Weihe Pál , Bergman Åke
Published: July 2005

Background

Persistent organic pollutants (POPs) in wildlife and humans remain a cause of global concern, both in regard to traditional POPs, such as the polychlorinated biphenyls (PCBs), and emerging POPs, such as the polybrominated diphenyl ethers (PBDEs). To determine the time related concentrations, we analyzed human milk for these substances at three time points between 1987 and 1999. Polychlorobiphenylols (OH-PCBs), the dominating class of PCB metabolites, some of which are known to be strongly retained in human blood, were also included in the assessment.

Methods

We obtained milk from the Faroe Islands, where the population is exposed to POPs from their traditional diet (which may include pilot whale blubber). In addition to three pools, nine individual samples from the last time point were also analyzed. After cleanup, partitioning of neutral and acidic compounds, and separation of chemical classes, the analyses were carried out by gas chromatography and/or gas chromatography/mass spectrometry.

Results

Compared to other European populations, the human milk had high PCB concentrations, with pool concentrations of 2300 ng/g fat 1987, 1600 ng/g fat in 1994, and 1800 ng/g fat in 1999 (based on the sum of eleven major PCB congeners). The nine individual samples showed great variation in PCB concentrations. The OH-PCBs were present in trace amounts only, at levels of approximately 1% of the PCB concentrations. The PBDE concentrations showed a clear increase over time, and their concentrations in human milk from 1999 are among the highest reported so far from Europe, with results of individual samples ranging from 4.7 to 13 ng/g fat

Conclusion

Although remote from pollution sources, the Faroe Islands show high concentrations of POPs in human milk, particularly PCBs, but also PBDEs. The PBDEs show increasing concentrations over time. The OH-PCB metabolites are poorly transferred to human milk, which likely is related to their acidic character.
An investigation into the psychometric properties of the Hospital Anxiety and Depression Scale in patients with breast cancer
Authors: Rodgers Jacqui , Martin Colin R , Morse Rachel C , Kendell Kate , Verrill Mark
Published: July 2005

Background

To determine the psychometric properties of the Hospital Anxiety and Depression Scale (HADS) in patients with breast cancer and determine the suitability of the instrument for use with this clinical group.

Methods

A cross-sectional design was used. The study used a pooled data set from three breast cancer clinical groups. The dependent variables were HADS anxiety and depression sub-scale scores. Exploratory and confirmatory factor analyses were conducted on the HADS to determine its psychometric properties in 110 patients with breast cancer. Seven models were tested to determine model fit to the data.

Results

Both factor analysis methods indicated that three-factor models provided a better fit to the data compared to two-factor (anxiety and depression) models for breast cancer patients. Clark and Watson's three factor tripartite and three factor hierarchical models provided the best fit.

Conclusion

The underlying factor structure of the HADS in breast cancer patients comprises three distinct, but correlated factors, negative affectivity, autonomic anxiety and anhedonic depression. The clinical utility of the HADS in screening for anxiety and depression in breast cancer patients may be enhanced by using a modified scoring procedure based on a three-factor model of psychological distress. This proposed alternate scoring method involving regressing autonomic anxiety and anhedonic depression factors onto the third factor (negative affectivity) requires further investigation in order to establish its efficacy.
Maternal nutrient restriction and the fetal left ventricle: Decreased angiotensin receptor expression
Authors: Gilbert Jeffrey S , Lang Alvin L , Nijland Mark J
Published: July 2005

Background

Adequate maternal nutrition during gestation is requisite for fetal nutrition and development. While a large group of epidemiological studies indicate poor fetal nutrition increases heart disease risk and mortality in later life, little work has focused on the effects of impaired maternal nutrition on fetal heart development. We have previously shown that 50% global nutrient restriction from 28–78 days of gestation (early to mid-pregnancy; term = 147 days) in sheep at mid-gestation retards fetal growth while protecting growth of heart and results in hypertensive male offspring at nine months of age. In the present study, we evaluate LV gene transcription using RNA protection assay and real-time reverse transcriptase polymerase chain reaction, and protein expression using western blot, of VEGF and AT1 and AT2 receptors for AngII at mid-gestation in fetuses from pregnant ewes fed either 100% (C) or 50% (NR) diet during early to mid-gestation.

Results

No difference between the NR (n = 6) and C (n = 6) groups was found in gene transcription of the AngII receptors. Immunoreactive AT1 (1918.4 +/- 154.2 vs. 3881.2 +/- 494.9; P < 0.01) and AT2 (1729.9 +/- 293.6 vs. 3043.3 +/- 373.2; P < 0.02) was decreased in the LV of NR fetuses compared to C fetuses. The LV of fetuses exposed to NR had greater transcription of mRNA for VEGF (5.42 ± 0.85 vs. 3.05 ± 0.19; P < 0.03) than respective C LV, while no change was observed in immunoreactive VEGF.

Conclusion

The present study demonstrates that VEGF, AT1 and AT2 message and protein are not tightly coupled, pointing to post-transcriptional control points in the mid gestation NR fetus. The present data also suggest that the role of VEGF and the renin-angiotensin system receptors during conditions inducing protected cardiac growth is distinct from the role these proteins may play in normal fetal cardiac growth. The present findings may help explain epidemiological studies that indicate fetuses with low birth weight carry an increased risk of mortality from coronary and cardiovascular disease, particularly if these individuals have reduced cardiovascular reserve due to an epigenetic decrease in vascularization.
Cost and cost-effectiveness of community based and health facility based directly observed treatment of tuberculosis in Dar es Salaam, Tanzania
Authors: Wandwalo Eliud , Robberstad Bjarne , Morkve Odd
Published: July 2005

Background

Identifying new approaches to tuberculosis treatment that are effective and put less demand to meagre health resources is important. One such approach is community based direct observed treatment (DOT). The purpose of the study was to determine the cost and cost effectiveness of health facility and community based directly observed treatment of tuberculosis in an urban setting in Tanzania.

Methods

Two alternative strategies were compared: health facility based directly observed treatment by health personnel and community based directly observed treatment by treatment supervisors. Costs were analysed from the perspective of health services, patients and community in the year 2002 in US $ using standard methods. Treatment outcomes were obtained from a randomised-controlled trial which was conducted alongside the cost study. Smear positive, smear negative and extra-pulmonary TB patients were included. Cost-effectiveness was calculated as the cost per patient successfully treated.

Results

The total cost of treating a patient with conventional health facility based DOT and community based DOT were $ 145 and $ 94 respectively. Community based DOT reduced cost by 35%. Cost fell by 27% for health services and 72% for patients. When smear positive and smear negative patients were considered separately, community DOT was associated with 45% and 19% reduction of the costs respectively. Patients used about $ 43 to follow their medication to health facility which is equivalent to their monthly income. Indirect costs were as important as direct costs, contributing to about 49% of the total patient's cost. The main reason for reduced cost was fewer number of visits to the TB clinic. Community based DOT was more cost-effective at $ 128 per patient successfully treated compared to $ 203 for a patient successfully treated with health facility based DOT.

Conclusion

Community based DOT presents an economically attractive option to complement health facility based DOT. This is particularly important in settings where TB clinics are working beyond capacity under limited resources.