julilili42/papers huggingface dataset:
Tirofiban (Aggrastat®) Protects Platelets and Decreases Platelet-Granulocyte Binding in an Extracorporeal Circulation Model
2006-04-26

Amongst the investigated drugs only GP IIb/IIIa inhibitors decreased activation, aggregation, and loss of platelets during ECC but acted differently on platelet-granulocyte interaction. A short-acting GP IIb/IIIa inhibitor with the potential to inhibit platelet activation and platelet-leukocyte interaction should be considered both for platelet protection and inhibition of platelet-mediated inflammation during ECC.
A New Wound-Based Severity Score for Diabetic Foot Ulcers: A prospective analysis of 1,000 patients
2006-04-27

The DUSS categorizes different ulcers into subgroups with specific severity and similar clinical outcome. Using this score, the probabilities for healing, amputation, need for surgery, and hospitalization are predictable with high accuracy. This might be useful for the anticipation of health care costs and for comparison of subgroups of patients in clinical studies.
Breast cancer proteomics by laser capture microdissection, sample pooling, 54‐cm IPG IEF, and differential iodine radioisotope detection
2006-04-27

Abstract The presence of progesterone receptor (PR) in estrogen receptor (ER)‐positive breast cancer is associated with a good prognosis, and indicates that tumors are likely to respond to tamoxifen. However, ER + /PR − tumors respond less well. To reveal the potential molecular mechanism of this phenomenon, we sought to identify differential protein abundances between invasive ductal carcinoma cells from cryopreserved ER + /PR + and ER + /PR − mammary tumor specimens. Because current proteomics methods are hampered in the examination of most primary human tumor samples by the extreme tissue heterogeneity, we used laser capture microdissection (LCM) to isolate tumor cells and developed a sample pooling strategy to analyze small sample protein lysates. Proteins from LCM‐harvested tumors were pooled into four sub‐pools from each condition of three tumors/sub‐pool, and proteins from respective paired sub‐pools were co‐electrophoresed by 2‐DE using 54‐cm IEF over pH 4–9. Abundance ratios were accurately quantified by a differential multiplex radioactive ProteoTope method at low attomole levels (∼3.6 &amp;&amp;mu;;g protein per labeling reaction, &lt;180 ng per multiplex protein sample per 54‐cm gel). Applying this approach, differentially displayed proteins were identified by MS using comigrating non‐radioactively labeled tumor proteins. They include decreased cytochrome b 5 and transgelin, and more abundant CRABP‐II, cyclophilin A, Neudesin, and hemoglobin in ER + /PR + tumors versus ER + /PR − providing a possible explanation for differential susceptibility against tamoxifen as a result of deregulated cytochrome b 5 ‐dependent metabolism. This study demonstrates the potential of ProteoTope and LCM to enable extremely sensitive and precise differential analyses from well‐defined primary clinical specimen.
ARLTS1 variants and melanoma risk
2006-04-27

Abstract Variants in the tumor suppressor gene ARLTS1 (ADP‐ribosylation factor‐like tumor‐suppressor gene 1) have been shown to influence familial cancer risk. Both Cys148Arg and Trp149Stop were associated with an increased risk of familial or high‐risk familial breast cancer, respectively. We studied the impact of these gene variants on melanoma risk, investigating 351 melanoma patients and 804 control subjects. While ARLTS1 Trp149Stop did not influence melanoma risk (OR = 0.83, 95% CI = 0.37–1.88, p = 0.65), Cys148Arg revealed a statistically significant association with an increased risk for heterozygous carriers (OR = 1.43, 95% CI = 1.05–1.95, p = 0.02). An additional risk enhancement, though statistically non‐significant, was observed in individuals with multiple melanomas (OR = 2.33, 95% CI = 0.87–6.26, p = 0.08). © 2006 Wiley‐Liss, Inc.
Synthesis and Anticoagulant Activities of Substituted 2,4‐Diketochromans, Biscoumarins, and Chromanocoumarins
2006-04-28

Abstract Different substituted 2,4‐diketochromans, biscoumarins, and chromanocoumarins are the final products when 4‐hydroxycoumarin and aromatic aldehydes containing hydroxyl group in o ‐, m, ‐ or p ‐position condense in boiling ethanol. We synthesized 14 compounds. Three of them are described for the first time. The X‐ray crystal structure analysis of 3‐[6‐oxo‐(6 H , 7 H )‐benzopyrano[4,3‐b]benzopyran‐7‐yl]‐4‐hydroxy‐2 H ‐1‐benzopyran‐2‐one 1 confirmed the structure of this compound. Acute toxicity studies of the compounds were performed on mice by oral and intraperitoneal administration. A comparative pharmacological study of the in vivo anticoagulant effect of the derivatives with respect to warfarin showed that the synthesized compounds have different anticoagulant activities. The most prospective compounds are 3‐(3′‐hydroxybenzylidene)‐2,4‐diketochroman 4 and 3,3′‐(2‐pyridylmethylene)‐bis‐4‐hydroxy‐2 H ‐1‐benzopyran‐2‐one 11 with low toxicity and dose‐dependent anticoagulant activity in vivo .
Immunocytochemical localization of 3‐methylcrotonyl‐CoA carboxylase in cultured ependymal, microglial and oligodendroglial cells
2006-04-28

Abstract To evaluate the ability of ependymal, microglial and oligodendroglial cells to degrade leucine, the presence of 3‐methylcrotonyl‐CoA carboxylase (MCC) was investigated in cultures of these cells. MCC is a biotin‐containing heterodimeric enzyme that is specific for the irreversible part of the leucine catabolic pathway. It has been reported previously that in cell culture MCC is expressed in astrocytes and a subpopulation of neurones. In the present study ependymal, microglial and oligodendroglial cell cultures, derived from the brains of newborn rats, were examined for the expression of MCC by RT–PCR, western blotting and immunocytochemistry. The results of RT–PCR and western blotting showed the presence of mRNA as well as protein of both subunits of MCC in ependymal, microglial and oligodendroglial cell cultures. Immunocytochemical investigation of the cellular and subcellular distribution of MCC demonstrated a mitochondrial location of MCC in all neuroglial cell types investigated. The ubiquitous expression of MCC in glial cells demonstrates the ability of the cells to engage in the catabolism of leucine transported into the brain, mainly for the generation of energy.
A systematic review on the diagnosis and treatment of primary (idiopathic) dystonia and dystonia plus syndromes: report of an EFNS/MDS‐ES Task Force
2006-05-01

To review the literature on primary dystonia and dystonia plus and to provide evidence‐based recommendations. Primary dystonia and dystonia plus are chronic and often disabling conditions with a widespread spectrum mainly in young people. Computerized MEDLINE and EMBASE literature reviews (1966–1967 February 2005) were conducted. The Cochrane Library was searched for relevant citations. Diagnosis and classification of dystonia are highly relevant for providing appropriate management and prognostic information, and genetic counselling. Expert observation is suggested. DYT‐1 gene testing in conjunction with genetic counselling is recommended for patients with primary dystonia with onset before age 30 years and in those with an affected relative with early onset. Positive genetic testing for dystonia (e.g. DYT‐1) is not sufficient to make diagnosis of dystonia. Individuals with myoclonus should be tested for the epsilon‐sarcoglycan gene (DYT‐11). A levodopa trial is warranted in every patient with early onset dystonia without an alternative diagnosis. Brain imaging is not routinely required when there is a confident diagnosis of primary dystonia in adult patients, whereas it is necessary in the paediatric population. Botulinum toxin (BoNT) type A (or type B if there is resistance to type A) can be regarded as first line treatment for primary cranial (excluding oromandibular) or cervical dystonia and can be effective in writing dystonia. Actual evidence is lacking on direct comparison of the clinical efficacy and safety of BoNT‐A vs. BoNT‐B. Pallidal deep brain stimulation (DBS) is considered a good option, particularly for generalized or cervical dystonia, after medication or BoNT have failed to provide adequate improvement. Selective peripheral denervation is a safe procedure that is indicated exclusively in cervical dystonia. Intrathecal baclofen can be indicated in patients where secondary dystonia is combined with spasticity. The absolute and comparative efficacy and tolerability of drugs in dystonia, including anticholinergic and antidopaminergic drugs, is poorly documented and no evidence‐based recommendations can be made to guide prescribing.
Carbon solubility in mantle minerals
2006-05-01

The solubility of carbon in olivine, enstatite, diopside, pyrope, MgAl2O4 spinel, wadsleyite, ringwoodite, MgSiO3–ilmenite and MgSiO3–perovskite has been quantified. Carbon-saturated crystals were grown from carbonatite melts at 900–1400 °C and 1.5 to ∼ 26 GPa in piston cylinder or multi-anvil presses using carbon enriched to > 99% in the 13C isotope. In upper mantle silicates, carbon solubility increases as a function of pressure to a maximum of ∼ 12 ppm by weight in olivine at 11 GPa. No clear dependence of carbon solubility on temperature, oxygen fugacity or iron content was observed. The observation that carbon solubility in olivine is insensitive to oxygen fugacity implies that the oxidation state of carbon in the carbonatite melt and in olivine is the same, i.e., carbon dissolves as C4+ in olivine. Carbon solubility in spinel MgAl2O4, transition zone minerals (wadsleyite and ringwoodite), MgSiO3–ilmenite and MgSiO3–perovskite are below the limit of detection of our SIMS-based analytical technique (i.e., below 30–200 ppb by weight). The differences in carbon solubilities between the various minerals studied appear to correlate with the polyhedral volume of the Si4+ site, consistent with a direct substitution of C4+ for Si4+. These results show that other, minor carbon-rich phases, rather than major, nominally volatile-free minerals, dominate the carbon budget within the bulk Earth's mantle. A significant fraction of total carbon could only be stored in silicates in a thin zone in the lowermost upper mantle, just above the transition zone, and only if the bulk carbon content is at the lower limit of published estimates. The carbon budget of the remaining mantle is dominated by carbonates and possibly diamond. The low melting point of carbonates and the high mobility of carbonate melts suggest that carbon distribution in the mantle may be highly heterogeneous, including the possibility of massive carbon enrichments on a local scale, particularly in the shallow subcontinental mantle.
Dexamethasone Induces Cell Death in Insulin-Secreting Cells, an Effect Reversed by Exendin-4
2006-05-01

Glucocorticoid excess induces hyperglycemia, which may result in diabetes. The present experiments explored whether glucocorticoids trigger apoptosis in insulin-secreting cells. Treatment of mouse β-cells or INS-1 cells with the glucocorticoid dexamethasone (0.1 μmol/l) over 4 days in cell culture increased the number of fractionated nuclei from 2 to 7 and 14%, respectively, an effect that was reversed by the glucocorticoid receptor antagonist RU486 (1 μmol/l). In INS-1 cells, dexamethasone increased the number of transferase-mediated dUTP nick-end labeling–staining positive cells, caspase-3 activity, and poly-(ADP-) ribose polymerase protein cleavage; decreased Bcl-2 transcript and protein abundance; dephosphorylated the proapoptotic protein of the Bcl-2 family (BAD) at serine155; and depolarized mitochondria. Dexamethasone increased PP-2B (calcineurin) activity, an effect abrogated by FK506. FK506 (0.1 μmol/l) and another calcineurin inhibitor, deltamethrin (1 μmol/l), attenuated dexamethasone-induced cell death. The stable glucagon-like peptide 1 analog, exendin-4 (10 nmol/l), inhibited dexamethasone-induced apoptosis in mouse β-cells and INS-1 cells. The protective effect of exendin-4 was mimicked by forskolin (10 μmol/l) but not mimicked by guanine nucleotide exchange factor with the specific agonist 8CPT-Me-cAMP (50 μmol/l). Exendin-4 did not protect against cell death in the presence of cAMP-dependent protein kinase (PKA) inhibition by H89 (10 μmol/l) or KT5720 (5 μmol/l). In conclusion, glucocorticoid-induced apoptosis in insulin-secreting cells is accompanied by a downregulation of Bcl-2, activation of calcineurin with subsequent dephosphorylation of BAD, and mitochondrial depolarization. Exendin-4 protects against glucocorticoid-induced apoptosis, an effect mimicked by forskolin and reversed by PKA inhibitors.
Auxofuran, a Novel Metabolite That Stimulates the Growth of Fly Agaric, Is Produced by the Mycorrhiza Helper Bacterium Streptomyces Strain AcH 505
2006-05-01

ABSTRACT The mycorrhiza helper bacterium Streptomyces strain AcH 505 improves mycelial growth of ectomycorrhizal fungi and formation of ectomycorrhizas between Amanita muscaria and spruce but suppresses the growth of plant-pathogenic fungi, suggesting that it produces both fungal growth-stimulating and -suppressing compounds. The dominant fungal-growth-promoting substance produced by strain AcH 505, auxofuran, was isolated, and its effect on the levels of gene expression of A. muscaria was investigated. Auxofuran and its synthetic analogue 7-dehydroxy-auxofuran were most effective at a concentration of 15 μM, and application of these compounds led to increased lipid metabolism-related gene expression. Cocultivation of strain AcH 505 and A. muscaria stimulated auxofuran production by the streptomycete. The antifungal substances produced by strain AcH 505 were identified as the antibiotics WS-5995 B and C. WS-5995 B completely blocked mycelial growth at a concentration of 60 μM and caused a cell stress-related gene expression response in A. muscaria . Characterization of these compounds provides the foundation for molecular analysis of the fungus-bacterium interaction in the ectomycorrhizal symbiosis between fly agaric and spruce.
A New Wound-Based Severity Score for Diabetic Foot Ulcers
2006-05-01

OBJECTIVE—Several well-accepted classification systems are available for diabetic foot ulcers. However, there are only a few and scientifically not validated severity scores. The aim of this study was to establish a new wound-based clinical scoring system for diabetic foot ulcers suitable for daily clinical practice anticipating chances for healing and risk of amputation. RESEARCH DESIGN AND METHODS—Four clinically defined parameters, namely palpable pedal pulses, probing to bone, ulcer location, and presence of multiple ulcerations, were prospectively assessed in 1,000 consecutive patients. In the next step, a new diabetic ulcer severity score (DUSS) was created from these parameters. Palpable pedal pulses were categorized by the absence (scored as 1) or presence (scored as 0) of pedal pulses, while probing to bone was defined as yes (scored as 1) or no (scored as 0). The site of ulceration was defined as toe (scored as 0) or foot (scored as 1) ulcer. Patients with multiple ulcerations were graded as 1 compared with those with single ulcers (scored as 0). The DUSS was calculated by adding these separate gradings to a theoretical maximum of 4. Wounds were followed-up for 365 days or until healing or amputation if earlier. Probability of healing and risk of amputation were calculated by the Kaplan-Meier method. RESULTS—Uni- and multivariate analyses showed a significantly higher probability of healing for patients with palpable pulses, no probing to bone, toe ulcers, and absence of multiple ulcerations. When patients were divided into subgroups with the same DUSS, we found significantly different probabilities for healing. We showed a decreasing probability of healing for ulcers with a high DUSS, concurrent with increasing amputation rates. An increase in the DUSS by one score point reduced the chance for healing by 35%. Similarly, the higher the ulcer score, the larger the initial wound area, the longer the wound history, and the more likely the need for surgery or hospitalization. CONCLUSIONS—The DUSS categorizes different ulcers into subgroups with specific severity and similar clinical outcome. Using this score, the probabilities for healing, amputation, need for surgery, and hospitalization are predictable with high accuracy. This might be useful for the anticipation of health care costs and for comparison of subgroups of patients in clinical studies.
The Genetics of Human Longevity
2006-05-01

Abstract: Aging is due to a complex interaction of genetic, epigenetic, and environmental factors, but a strong genetic component appears to have an impact on survival to extreme ages. In order to identify “longevity genes” in humans, different strategies are now available. In our laboratory, we performed association studies on a variety of “candidate” polymorphisms in Italian centenarians. Many genes/polymorphisms gave negative results, while others showed a positive association with human longevity and a sometimes‐positive association with unsuccessful aging (myocardial infarction, Alzheimer's disease, and type 2 diabetes). Results regarding genes involved in inflammation (IL‐1 cluster, IL‐6, IL‐10, TNF‐α, TGF‐β, TLR‐4, PPARγ), insulin/IGF‐1 signaling pathway and lipid metabolism (apolipoproteins, CETP, PON1), and oxidative stress (p53, p66 shc ) will be described. In addition, a strong role of the interaction between nuclear and mitochondrial genomes (mtDNA haplogroups and the C150T mutation) emerged from our findings. Thus, the genetics of human longevity appears to be quite peculiar in a context where antagonistic pleiotropy can play a major role and genes can have a different biological role at different ages.
Auxin Immunolocalization Implicates Vesicular Neurotransmitter-Like Mode of Polar Auxin Transport in Root Apices
2006-05-01

Immunolocalization of auxin using a new specific antibody revealed, besides the expected diffuse cytoplasmic signal, enrichments of auxin at end-poles (cross-walls), within endosomes and within nuclei of those root apex cells which accumulate abundant F-actin at their end-poles. In Brefeldin A (BFA) treated roots, a strong auxin signal was scored within BFA-induced compartments of cells having abundant actin and auxin at their end-poles, as well as within adjacent endosomes, but not in other root cells. Importantly, several types of polar auxin transport (PAT) inhibitors exert similar inhibitory effects on endocytosis, vesicle recycling, and on the enrichments of F-actin at the end-poles. These findings indicate that auxin is transported across F-actin-enriched end-poles (synapses) via neurotransmitter-like secretion. This new concept finds genetic support from the semaphore1, rum1 and rum1/lrt1 mutants of maize which are impaired in PAT, endocytosis and vesicle recycling, as well as in recruitment of F-actin and auxin to the auxin transporting end-poles. Although PIN1 localizes abundantly to the end-poles, and they also fail to support the formation of in these mutants affected in PAT, auxin and F-actin are depleted from their end-poles which also fail to support formation of the large BFA-induced compartments.
Phylogeny of the Quambalariaceae fam. nov., including important Eucalyptus pathogens in South Africa and Australia
2006-05-01

The genus Quambalaria consists of plant-pathogenic fungi causing disease on leaves and shoots of species of Eucalyptus and its close relative, Corymbia. The phylogenetic relationship of Quambalaria spp., previously classified in genera such as Sporothrix and Ramularia, has never been addressed. It has, however, been suggested that they belong to the basidiomycete orders Exobasidiales or Ustilaginales. The aim of this study was thus to consider the ordinal relationships of Q. eucalypti and Q. pitereka using ribosomal LSU sequences. Sequence data from the ITS nrDNA were used to determine the phylogenetic relationship of the two Quambalaria species together with Fugomyces (= Cerinosterus) cyanescens. In addition to sequence data, the ultrastructure of the septal pores of the species in question was compared. From the LSU sequence data it was concluded that Quambalaria spp. and F. cyanescens form a monophyletic clade in the Microstromatales, an order of the Ustilaginomycetes. Sequences from the ITS region confirmed that Q. pitereka and Q. eucalypti are distinct species. The ex-type isolate of F. cyanescens, together with another isolate from Eucalyptus in Australia, constitute a third species of Quambalaria, Q. cyanescens (de Hoog & G.A. de Vries) Z.W. de Beer, Begerow & R. Bauer comb. nov. Transmission electron-microscopic studies of the septal pores confirm that all three Quambalaria spp. have dolipores with swollen lips, which differ from other members of the Microstromatales (i.e. the Microstromataceae and Volvocisporiaceae) that have simple pores with more or less rounded pore lips. Based on their unique ultrastructural features and the monophyly of the three Quambalaria spp. in the Microstromatales, a new family, Quambalariaceae Z.W. de Beer, Begerow & R. Bauer fam. nov., is described.
Human Immunosenescence
2006-05-01

Abstract: The rate of acceleration of the frequency of death due to cardiovascular disease or cancer increases with age from middle age up to around 75–80 years, plateauing thereafter. Mortality due to infectious disease, however, does not plateau, but continues to accelerate indefinitely. The elderly are particularly susceptible to novel infectious agents such as SARS, as well as to previously encountered pathogens. Why is this? The elderly commonly possess oligoclonal expansions of T cells, especially of CD8 cells, which, surprisingly, are associated with cytomegalovirus (CMV) seropositivity. This in turn is associated with many of the same phenotypic and functional alterations to T cell immunity that have been suggested as biomarkers of immune system aging. We suggest that, in fact, CMV, not age per se , is the prime driving force behind many or most of the oligoclonal expansions and altered phenotypes and functions of CD8 cells in the elderly. Thus, the manner in which CMV and the host immune system interact (over which period? on which genetic background? with which co‐infections?) is critical in determining the “age” of adaptive immunity and hence human longevity. In this respect, immunosenescence is infectious.