bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractCytokines 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

AbstractTelomerase 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

AbstractThe 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

AbstractErdheim-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

Abstract

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

Abstract
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

Abstract

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

Abstract
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

Abstract
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

Abstract
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

Abstract

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

Abstract

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

AbstractWith 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.