gebhart/patrepeval huggingface dataset:
Targeted ablation of Fgf23 demonstrates an essential physiological role of FGF23 in phosphate and vitamin D metabolism (2004)

Inorganic phosphate is essential for ECM mineralization and also as a constituent of important molecules in cellular metabolism. Investigations of several hypophosphatemic diseases indicated that a hormone-like molecule probably regulates serum phosphate concentration. FGF23 has recently been recognized as playing important pathophysiological roles in several hypophosphatemic diseases. We present here the evidence that FGF23 is a physiological regulator of serum phosphate and 1,25-dihydroxyvitamin D (1,25[OH](2)D) by generating FGF23-null mice. Disruption of the Fgf23 gene did not result in embryonic lethality, although homozygous mice showed severe growth retardation with abnormal bone phenotype and markedly short life span. The Fgf23(–/–) mice displayed significantly high serum phosphate with increased renal phosphate reabsorption. They also showed an elevation in serum 1,25(OH)(2)D that was due to the enhanced expression of renal 25-hydroxyvitamin D-1α-hydroxylase (1α-OHase) from 10 days of age. These phenotypes could not be explained by currently known regulators of mineral homeostasis, indicating that FGF23 is essential for normal phosphate and vitamin D metabolism.
Genetic epidemiology of rheumatoid arthritis. (1995)

We conducted family studies and segregation analyses of rheumatoid arthritis (RA) that were based on consecutive patients with RA ascertained without regard to family history or known risk factors. First-degree relatives from 135 simplex and 30 multiplex families were included in the analyses. A highly penetrant recessive major gene, with a mutant allele frequency of .005, was identified as the most parsimonious genetic risk factor. Significant evidence for heterogeneity in risk for RA was observed for proband gender but not for proband age at onset. Kaplan-Meier risk analysis demonstrated significant evidence for differences in the distribution of risk among first-degree relatives. These analyses demonstrated that both proband gender and age at onset are important risk factors but that proband gender appears to be the more important determinant of risk, with relatives of male probands having the greatest cumulative risk for RA. In addition, log-linear modeling identified proband gender, familiality (multiplex or simplex), and an interaction term between these two variables as being adequate to define the distribution of risk in families. The pattern of risk for RA among susceptible individuals and its inheritance is thus heterogeneous. For future genetic analyses, families with an excess of affected males having a young age at onset may be the most informative in identifying the putative recessive gene and its modifiers.
Religious Lawyering Critique, The AALS Presentations (2005)

The Ussing chamber technique has contributed significantly to our understanding of the role of ion transport in the pathogenesis of human diseases like cystic fibrosis (CF). Here, we summarize protocols developed to study the Cl- channel function of the cystic fibrosis transmembrane conductance regulator (CFTR) protein in rectal biopsies from normal individuals and CF patients. These protocols can be applied to study the function and pharmacological modulation of wild-type and mutant CFTR in the context of the native epithelium. Together with sweat testing and genetic analyses, these functional measurements may aid in establishing a diagnosis of CF.
Simultaneous spatial and spectral selective excitation (1990)

Using a k-space interpretation of small-tip excitation, a single excitation pulse has been designed that is simultaneously selective in space and resonant frequency. An analytic expression for the response of this pulse has been derived. The pulse has been implemented on a 1.5-T imaging system. The pulse has been applied to a rapid gradient-echo imaging sequence that forms both water and fat images within a breath-holding interval. These rapid images are free of the chemical shift artifacts at organ boundaries that typically afflict conventional rapid images. The pulse can be applied to a variety of other sequences, such as multislice water/fat sequences and rapid k-space scanning sequences.
Characterization of human SCD2, an oligomeric desaturase with improved stability and enzyme activity by cross-linking in intact cells (2005)

SCD (stearoyl-CoA desaturase) catalyses the conversion of saturated fatty acids into mono-unsaturated fatty acids, a critical step involved in lipid metabolism and various other biological functions. In the present study, we report the identification and characterization of a human gene that encodes a novel SCD enzyme (hSCD2). The hSCD2 gene codes for a 37.5-kDa protein that shares 61% and 57% sequence identity with the human SCD1 and mouse SCD2 enzymes respectively. The recombinant hSCD2 enzyme expressed in mammalian and Sf9 insect cells efficiently catalysed desaturation of both stearoyl- and palmitoyl-CoAs to the corresponding mono-unsaturated fatty acids. In comparison with the hSCD1 gene that is predominantly expressed in liver, hSCD2 is most abundantly expressed in pancreas and brain. Additionally, hSCD2 transcripts from adult and foetal tissues exhibit different sizes because of alternative splicing in the non-coding region, suggesting that hSCD2 expression is developmentally regulated. The recombinant human SCD2 and SCD1 transiently expressed in COS-7 cells exhibited as oligomeric proteins that consist of homodimers and oligomers when resolved by SDS/PAGE. The complex formation was independent of SCD protein expression levels, as supported by a relatively constant ratio of the level of dimers and oligomers to that of the monomers from COS-7 cells transiently transfected with different amounts of SCD expression vectors. Furthermore, treatment of intact COS-7 cells with a cross-linking reagent resulted in dose-dependent increases in the levels of SCD protein and activity, suggesting that oligomerization may play an important role in regulating the stability of SCD enzymes.
Evaluation of consistency among different electrical impedance indices of relative cerebral blood flow in normal resting individuals (1989)

Significant correlation was observed, in normal resting individuals, of interregional variation of classical amplitude-dependent electrical impedance indices of cerebral blood flow (CBF) with three quantitative rheographic measures of cerebral blood flow which have been themselves radioisotopically validated. Since these amplitude-related CBF indices are derived from the Nyboer model relating blood volume changes to change of impedance, the data support the correctness and applicability of this model to the head. Interrelationship among the CBF parameters obtained with the use of this technique was found to be markedly affected by differing electrode placements; it was not apparently affected by extracranial circulation. It is concluded that under proper recording conditions, several assumptions underlying rheoencephalography are consistent and that it may be a useful tool for the study of relative regional cerebral blood flow in normal individuals.
Rapid Divergence of the Ecdysone Receptor in Diptera and Lepidoptera Suggests Coevolution Between ECR and USP-RXR (2003)

Ecdysteroid hormones are major regulators in reproduction and development of insects, including larval molts and metamorphosis. The functional ecdysone receptor is a heterodimer of ECR (NR1H1) and USP-RXR (NR2B4), which is the orthologue of vertebrate retinoid X receptors (RXR alpha, beta, gamma). Both proteins belong to the superfamily of nuclear hormone receptors, ligand-dependent transcription factors that share two conserved domains: the DNA-binding domain (DBD) and the ligand-binding domain (LBD). In order to gain further insight into the evolution of metamorphosis and gene regulation by ecdysone in arthropods, we performed a phylogenetic analysis of both partners of the heterodimer ECR/USP-RXR. Overall, 38 USP-RXR and 19 ECR protein sequences, from 33 species, have been used for this analysis. Interestingly, sequence alignments and structural comparisons reveal high divergence rates, for both ECR and USP-RXR, specifically among Diptera and Lepidoptera. The most impressive differences affect the ligand-binding domain of USP-RXR. In addition, ECR sequences show variability in other domains, namely the DNA-binding and the carboxy-terminal F domains. Our data provide the first evidence that ECR and USP-RXR may have coevolved during holometabolous insect diversification, leading to a functional divergence of the ecdysone receptor. These results have general implications on fundamental aspects of insect development, evolution of nuclear receptors, and the design of specific insecticides.
Amplified primer extension assay for psoralen photoproducts provides a sensitive assay for a (CG)6TA(CG)2(TG)8 Z-DNA torsionally tuned probe: Preferential psoralen photobinding to one strand of a B-Z junction (1993)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTAmplified primer extension assay for psoralen photoproducts provides a sensitive assay for a (CG)6TA(CG)2(TG)8 Z-DNA torsionally tuned probe: Preferential psoralen photobinding to one strand of a B-Z junctionRobert W. Hoepfner and Richard R. SindenCite this: Biochemistry 1993, 32, 29, 7542–7548Publication Date (Print):July 1, 1993Publication History Published online1 May 2002Published inissue 1 July 1993https://pubs.acs.org/doi/10.1021/bi00080a028https://doi.org/10.1021/bi00080a028research-articleACS PublicationsRequest reuse permissionsArticle Views58Altmetric-Citations4LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
FEEDING AWAY INFLAMMATION – CONJUGATED LINOLEIC ACIDS DECREASE PANCREATIC PHOSPHOLIPASE A2 ACTIVITY* (2007)

ABSTRACT Conjugated linoleic acids (CLAs) are positional and geometric isomers of linoleic acid derived from food, mainly from milk and meat products. CLAs are ligands of peroxisome proliferator‐activated gamma receptors. Phospholipases A 2 (PLA 2 ) represent a diverse group of enzymes that catalyze the hydrolysis of ester bonds at the sn ‐2 position of membrane phospholipids and release fatty acids and lysophospholipids. The objective of the study was to answer the question whether the release of linoleic acid by pancreatic PLA 2 may change in the CLA‐containing environment. In this study, linoleic acid released by pancreatic PLA 2 was a substrate for purified lipoxygenase – an enzyme converting it into hydroxylated derivatives including 9‐ and 13‐hydroxyoctadecadienoic acid (9‐,13‐HODE). In this method, the activity of PLA 2 was determined by high‐performance liquid chromatography. In vitro incubation of hog PLA 2 with CLA contributed to a noticeable fall in the synthesis of HODEs ( P = 0.003; Kruskal–Wallis test). The concentration of HODEs decreased by 40.2% (for the cis ‐9, trans ‐11 CLA isomer; P = 0.007, Mann–Whitney test, n = 5) and by 27% (for the trans ‐10, cis ‐12 CLA isomer; P = 0.007, Mann–Whitney test, n = 5) as compared with the control (enzyme incubated without CLA). The inhibition exerted by cis ‐9, trans ‐11 CLA isomer was significantly greater than that by trans ‐10, cis ‐12 CLA isomer ( P = 0.032, Mann–Whitney test, n = 5). PRACTICAL APPLICATIONS This study is an attempt to clarify the response to the question whether some food ingredients such as conjugated linoleic acid (CLA) may be useful as an agent supporting the treatment of gastrointestinal disorders. It was observed under in vitro conditions that CLA isomers inhibited the phosphatidylcholine hydrolysis. By using purified enzymes, CLA was shown to contribute to local reduction of availability of linoleic acid and its metabolites (9‐ and 13‐hydroxyoctadecadienoic acid) through inhibition of phospholipid hydrolysis.
The Death of Human Cancer Cells Following Photodynamic Therapy: Apoptosis Competence is Necessary for Bcl‐2 Protection but not for Induction of Autophagy† (2007)

Photodynamic therapy (PDT) is an efficient inducer of apoptosis in many types of cells, except in cells deficient in one or more of the factors that mediate apoptosis. Recent reports have identified autophagy as a potential alternative cell death process following PDT. Here we investigated the occurrence of autophagy after PDT with the photosensitizer Pc 4 in human cancer cells that are deficient in the pro-apoptotic factor Bax (human prostate cancer DU145 cells) or the apoptosis mediator caspase-3 (human breast cancer MCF-7v cells) and in apoptosis-competent cells (MCF-7c3 cells that stably overexpress human pro-caspase-3 and Chinese hamster ovary CHO 5A100 cells). Further, each of the cell lines was also studied with and without stably overexpressed Bcl-2. Autophagy was identified by electron microscopic observation of the presence of double-membrane-delineated autophagosomal vesicles in the cytosol and by immunoblot observation of the Pc 4-PDT dose- and time-dependent increase in the level of LC3-II, a component of the autophagosomal membrane. Autophagy was observed in all of the cell lines studied, whether or not they were capable of typical apoptosis and whether or not they overexpressed Bcl-2. The presence of stably overexpressed Bcl-2 in the cells protected against PDT-induced apoptosis and loss of clonogenicity in apoptosis-competent cells (MCF-7c3 and CHO 5A100 cells). In contrast, Bcl-2 overexpression did not protect against the development of autophagy in any of the cell lines or against loss of clonogenicity in apoptosis-deficient cells (MCF-7v and DU145 cells). Furthermore, 3-methyladenine and wortmannin, inhibitors of autophagy, provided greater protection against loss of viability to apoptosis-deficient than to apoptosis-competent cells. The results show that autophagy occurs during cell death following PDT in human cancer cells competent or not for normal apoptosis. Only the apoptosis-competent cells are protected by Bcl-2 against cell death.
Enzymatic Assays for the Diagnosis of Bradykinin-Dependent Angioedema (2013)

The amidase assay represents a diagnostic tool to help physicians in the decision to distinguish between BK-related and -unrelated AE.
Expansion of FOXP3high regulatory T cells by human dendritic cells (DCs) in vitro and after injection of cytokine-matured DCs in myeloma patients (2006)

CD4(+)CD25(+)FOXP3(+) regulatory T cells (Treg's) play an important role in the maintenance of immune tolerance. The mechanisms controlling the induction and maintenance of Treg's in humans need to be defined. We find that human myeloid dendritic cells (DCs) are superior to other antigen presenting cells for the maintenance of FOXP3(+) Treg's in culture. Coculture of DCs with autologous T cells leads to an increase in both the number of Treg's, as well as the expression of FOXP3 protein per cell both in healthy donors and myeloma patients. DC-mediated expansion of FOXP3(high) Treg's is enhanced by endogenous but not exogenous interleukin-2 (IL-2), and DC-T-cell contact, including the CD80/CD86 membrane costimulatory molecules. DCs also stimulate the formation of Treg's from CD25(-) T cells. The efficacy of induction of Treg's by DCs depends on the nature of the DC maturation stimulus, with inflammatory cytokine-treated DCs (Cyt-DCs) being the most effective Treg inducers. DC-induced Treg's from both healthy donors and patients with myeloma are functional and effectively suppress T-cell responses. A single injection of cytokine-matured DCs led to rapid enhancement of FOXP3(+) Treg's in vivo in 3 of 3 myeloma patients. These data reveal a role for DCs in increasing the number of functional FOXP3(high) Treg's in humans.
Analytical expression for temporal width characterization of radiation-induced pulse noises in SOI CMOS logic gates (2009)

Radiation-induced pulse noises called single-event transients, SETs, are becoming a serious soft-error source for logic VLSIs. Analytical models explicitly expressing the relationship between the pulse width and radiation/device/circuit parameters are desired as guidelines to develop optimized countermeasures. A simple mathematical expression is devised for characterizing SET pulse widths in SOI CMOS technologies. It is based on the physical mechanisms of the SETs and on the idea of Moll's storage time. Device simulations demonstrate that the expression explains pulse-width trends properly for large radiation-induced noise charges.
A randomized clinical trial on the benefit of adhesiolysis in patients with intraperitoneal adhesions and chronic pelvic pain (1992)

Adhesiolysis for the treatment of pelvic pain is not indicated in women with light or moderate degree pelvic adhesions. It may be beneficial in those with severe adhesions involving the intestinal tract.
Angiogenesis by Implantation of Peripheral Blood Mononuclear Cells and Platelets Into Ischemic Limbs (2002)

This study demonstrated that implantation of PBMNCs and platelets into ischemic limbs effectively induces collateral vessel formation by supplying angiogenic factors (mainly VEGF) and cytokines, suggesting that this cell therapy is useful as a novel strategy for therapeutic angiogenesis.
Human HSP27 is phosphorylated at serines 78 and 82 by heat shock and mitogen-activated kinases that recognize the same amino acid motif as S6 kinase II. (1992)

The intracellular concentration of the 27-kDa mammalian heat shock protein, HSP27, increases several-fold after heat and other metabolic stresses and is closely associated with the acquisition of thermotolerance. Posttranslational modifications may also affect the function of HSP27. Heat shock of HeLa cell cultures, or treatment with arsenite, phorbol ester, or tumor necrosis factor, caused a rapid phosphorylation of preexisting HSP27 and the appearance of three phosphorylated isoforms, HSP27 B, C, and D. Digestion with trypsin and fractionation of the peptides by reverse phase high performance liquid chromatography revealed three 32P-labeled phosphopeptides. Microsequence analysis identified peak I as Ala76-Leu77-Ser78-Arg79 and peak II as Gln80-Leu81-Ser82-Ser83-Gly84-Val85- Ser86-Glu87-Ile88-Arg89; peak III contained the undigested peptide pair Ala76-Arg89. Ser82 was the major site and Ser78 the minor site of phosphorylation. Mutant proteins with Ser78 or Ser82 altered to glycine or Ser78-Ser82 double mutants were phosphorylated to reduced extents in vivo after heat or arsenite treatment. Ser78 and Ser82 (and Ser15) occur in the sequence motif RXXS, which is recognized by ribosomal protein S6 kinase II. Mitogenic stimulation of serum-deprived, Go-arrested Chinese hamster cells with serum, thrombin, or fibroblast growth factor also stimulated phosphorylation of HSP27 Ser78 and Ser82, and mitogenic stimulation and heat shock activated protein kinase activities that phosphorylated HSP27 and protein S6 in vitro. These results suggest that HSP27 may exert phosphorylation-activated functions linked with growth signaling pathways in unstressed cells. A homeostatic function at this level could protect cells from adverse effects of signal transduction systems which may be activated inappropriately during stress.
Genetic identification of exported proteins in Streptococcus pneumoniae (1993)

A strategy was developed to mutate and genetically identify exported proteins in Streptococcus pneumoniae. Vectors were created and used to screen pneumococcal DNA in Escherichia coli and S. pneumoniae for translational gene fusions to alkaline phosphatase (PhoA). Twenty five PhoA+ pneumococcal mutants were isolated and the loci from eight of these mutants showed similarity to known exported or membrane-associated proteins. Homologues were found to: (i) protein-dependent peptide permeases, (ii) penicillin-binding proteins, (iii) Clp proteases, (iv) two-component sensor regulators, (v) the phosphoenolpyruvate: carbohydrate phosphotransferases permeases, (vi) membrane-associated dehydrogenases, (vii) P-type (E1E2-type) cation transport ATPases, (viii) ABC transporters responsible for the translocation of the RTX class of bacterial toxins. Unexpectedly one PhoA+ mutant contained a fusion to a member of the DEAD protein family of ATP-dependent RNA helicases suggesting export of these proteins.
Retroviral gene transfer into primary hepatocytes: implications for genetic therapy of liver-specific functions. (1987)

The liver is an important target for potential gene therapy because of the critical role it plays in intermediary metabolism and synthesis of serum proteins. We report the use of retroviral vectors for transfer of recombinant genes into primary mouse hepatocytes. Hepatocytes were grown in a defined serum-free medium and expressed liver-specific functions for up to 14 days. Hepatocytes were transformed to Genticin (G418) resistance by infection with recombinant retroviruses carrying the Tn5 neomycin-resistance gene. The G418-resistant cells exhibited characteristic hepatocyte morphology and continued to express liver-specific gene function. A retrovirus that expresses neomycin resistance driven by a herpes simplex thymidine kinase promoter produced the most efficient transformation compared with viruses using the retroviral long terminal repeat promoter or the simian virus 40 early-region promoter. These experiments indicate that primary hepatocytes can be successfully cultured and transformed with recombinant genes using retroviral vectors. These results provide a model for future somatic gene replacement therapy in which functional genes can be introduced into hepatocytes by viral-mediated gene transfer.
Diastolic Heart Failure: A Concise Review (2013)

The concept of "diastolic" heart failure grew out of the observation that many patients who have the symptoms and signs of heart failure had an apparently normal left ventricular (LV) ejection fraction. Thus it was assumed that since systolic function was "preserved" the problem must lie in diastole, although it is not clear by whom or when this assumption was made. Nevertheless, many guidelines followed on how to diagnose "diastolic" heart failure backed up by indicators of diastolic dysfunction derived from Doppler echoardiography. Diastolic heart failure is associated with a lower annual mortality rate of approximately 8% as compared to annual mortality of 19% in heart failure with systolic dysfunction, however, morbidity rate can be substantial. Thus, diastolic heart failure is an important clinical disorder mainly seen in the elderly patients with hypertensive heart disease. Early recognition and appropriate therapy of diastolic dysfunction is advisable to prevent further progression to diastolic heart failure and death. There is no specific therapy to improve LV diastolic function directly. Medical therapy of diastolic dysfunction is often empirical and lacks clear-cut pathophysiologic concepts. Nevertheless, there is growing evidence that calcium channel blockers, beta-blockers, ACE-inhibitors and ARB as well as nitric oxide donors can be beneficial. Treatment of the underlying disease is currently the most important therapeutic approach.