gebhart/patrepeval huggingface dataset:
Comparison of Risperidone and Placebo for Psychosis and Behavioral Disturbances Associated With Dementia (1999)

Risperidone significantly improved symptoms of psychosis and aggressive behavior in patients with severe dementia. Results show that 1 mg/day of risperidone is an appropriate dose for most elderly patients with dementia.
PairWise and SearchWise: Finding the Optimal Alignment in a Simultaneous Comparison of a Protein Profile against All DNA Translation Frames (1996)

DNA translation frames can be disrupted for several reasons, including: (i) errors in sequence determination; (ii) RNA processing, such as intron removal and guide RNA editing; (iii) less commonly, polymerase frameshifting during transcription or ribosomal frameshifting during translation. Frameshifts frequently confound computational activities involving homologous sequences, such as database searches and inferences on structure, function or phylogeny made from multiple alignments. A dynamic alignment algorithm is reported here which compares a protein profile (a residue scoring matrix for one or more aligned sequences) against the three translation frames of a DNA strand, allowing frameshifting. The algorithm has been incorporated into a new package, WiseTools, for comparison of biological sequences. A protein profile can be compared against either a DNA sequence or a protein sequence. The program PairWise may be used interactively for alignment of any two sequence inputs. SearchWise can perform combinations of searches through DNA or protein databases by a protein profile or DNA sequence. Routine application of the programs has revealed a set of database entries with frameshifts caused by errors in sequence determination.
Human gastric mucin. Identification of a unique species by expression cloning. (1993)

Gastric mucin is a large glycoprotein which is thought to play a major role in the protection of the gastrointestinal tract from acid, proteases, pathogenic microorganisms, and mechanical trauma. In this paper we describe the isolation by expression cloning and characterization of cDNAs which code for human gastric mucin. The cDNA sequence is characterized by a tandem repeat region whose individual repeat unit is 507 base pairs (169 amino acids) long. The translated sequence is rich in threonine, serine, and proline (31, 18, and 15%, respectively) and contains a relatively large amount of histidine (7.1%) and alanine (5.6%). RNA blot analysis shows a polydisperse pattern which is characteristic of mucins. Expression of this gene is highest in the stomach and gall bladder, with weaker expression in the terminal ileum and right colon. This expression pattern is different from other human mucins and indicates that this gene codes for a unique mucin. Fluorescence in situ hybridization techniques have localized this gene to chromosome 11p15.4-11p15.5. This is the third mucin to be localized to the 11p15 region and suggests a clustering of secretory mucin genes. We propose that this gene for human gastric mucin be called MUC6.
Genetic Definition and Sequence Analysis of Arabidopsis Centromeres (1999)

High-precision genetic mapping was used to define the regions that contain centromere functions on each natural chromosome in Arabidopsis thaliana. These regions exhibited dramatic recombinational repression and contained complex DNA surrounding large arrays of 180-base pair repeats. Unexpectedly, the DNA within the centromeres was not merely structural but also encoded several expressed genes. The regions flanking the centromeres were densely populated by repetitive elements yet experienced normal levels of recombination. The genetically defined centromeres were well conserved among Arabidopsis ecotypes but displayed limited sequence homology between different chromosomes, excluding repetitive DNA. This investigation provides a platform for dissecting the role of individual sequences in centromeres in higher eukaryotes.
Monoclonal antibody that neutralizes pertussis toxin activities. (2007)

Pertussis or whooping cough is a disease with high mortality among infants and small children. The disease is caused by infection of the respiratory tract by a gram negative bacterium, Bordetella pertussis. The superficial colonized bacteria produce a myriad of toxins which enter the circulation causing various pathophysiologicalal changes in the host. Although antimicrobial therapy reduces the number of the coughed out bacteria and also the infectious time of the infected host, but it is not effective in amelioration of the clinical manifestations as the pertussis morbidity is due principally to the pertussis toxin (PT). Antibody based-therapy is frequently practiced in conjunction with other supportive measure to resuscitate the patient. Nevertheless, human derived antiserum against PT is of the limited supply and the ethical concern. Thus in this study a hybridoma clone, i.e. clone PT6-2G6, secreting monoclonal antibody (MAb) specific to the S1 subunit, the active enzyme of the PT that intracellularly ADP-ribosylates the host Gi-protein, was produced. The MAbPT6-2G6 inhibited the in vitro hemagglutination of chicken erythrocytes which is the activity of the B oligomer of PT; thus we hypothesize that the MAb bound to its epitope on the S1 subunit and stereologically hinders the binding sites of the B subunits. The MAb also inhibited ex vivo Chinese hamster ovarian cell clustering and neutralized the in vivo leucocytosis- promotion in mice which are usually mediated by intracellular S1 subunit. The large molecular nature of the intact MAb and its molecular hydrophilicity led us to speculate that the observed PT neutralizing activities of the MAb were due to interfering with the cellular entry of the S1 rather than the intracellular enzyme neutralizing activity per se. While further experiments are needed to pinpoint the MAb neutralizing activity and to identify the amino acid sequence and location of the MAbPT6-2G6 epitope, our findings indicate that this murine MAb, in its humanized-version, should have high therapeutic potential for pertussis.
Atopic Dermatitis in Animals and People: An Update and Comparative Review (2017)

Atopic dermatitis is an extremely common, pruritic, and frustrating disease to treat in both people and animals. Atopic dermatitis is multifactorial and results from complex interactions between genetic and environmental factors. Much progress has been done in recent years in terms of understanding the complex pathogenesis of this clinical syndrome and the identification of new treatments. As we learn more about it, we appreciate the striking similarities that exist in the clinical manifestations of this disease across species. Both in animals and people, atopic disease is becoming increasingly common and important similarities exist in terms of immunologic aberrations and the propensity for allergic sensitization. The purpose of this review is to highlight the most recent views on atopic dermatitis in both domestic species and in people emphasizing the similarities and the differences. A comparative approach can be beneficial in understanding the natural course of this disease and the variable response to existing therapies.
Effects of vitamin D deprivation and 1,25-dihydroxyvitamin D3 treatment on ion release from rat tibiae in vitro. (1986)

Skeletal effects of dietary vitamin D and of 1,25-dihydroxyvitamin D3[1,25(OH)2D3] in vivo and in vitro were investigated using bones from vitamin D-deficient suckling rats. Tibiae from 19- to 21-day-old pups were incubated for up to 8 h in a defined medium and the net releases of Ca, inorganic phosphate (Pi) and Mg into and from the bones were determined. The pups were delivered and nursed by mothers fed either a diet containing vitamin D3 (+D) or a D-free diet (-D) starting on the sixth day of pregnancy. Effects of metabolic inhibition with iodoacetic acid (IAA, 1 mM); of elevated medium Pi concentration (2 mM); and of 1,25(OH)2D3 in vitro (2 and 10 ng/ml of medium) or in vivo (500 ng/mother ip, 2x) were evaluated. Although no effects of vitamin D on glucose metabolism or net Pi release were seen, tibiae from -D pups showed a marked decrease in net Ca release (up to 70%), while net Mg release was increased by 27%. IAA completely inhibited net Ca release in this system, had no effect on net Pi release, and reduced lactate production and net Mg release by 86 and 33%, respectively. Elevating the medium Pi concentration from 1 to 2 mM did not affect the differences between +D and -D bones. Treatment with 1,25(OH)2D3 in vitro and in vivo returned ion releases by the -D tibiae partly or completely to the +D levels. The results support the following conclusions: (1) vitamin D deficiency during suckling reduces net Ca release and increases net Mg release from bone which may contribute to the changes in circulating concentrations of these ions seen in D deficiency; (2) these effects on bone appear to be specific for Ca and Mg, since the vitamin has little or no effect on net Pi release; (3) net Ca and Mg release from rat bone in vitro presumably are energy-dependent processes, while net Pi release is not; and (4) 1,25(OH)2D3 can affect net Ca and Mg release from -D bones by a direct action.
Pharmacokinetics of tramadol and bioavailability of enteral tramadol formulations. 3rd Communication: suppositories. (1998)

The pharmacokinetics and the absolute bioavailability of tramadol hydrochloride (CAS 36282-47-0) after rectal administration of tramadol suppositories (Tramal) were determined in a balanced crossover study in 10 female volunteers in comparison with the intravenous injection. Each fasting volunteer received two single doses of 100 mg tramadol-HCl, one rectally (1 suppository) and one intravenously (2 ml of a solution for injection). The formulations were administered in the morning, the washout period was one week. Serum concentrations of tramadol-HCl were determined by gas chromatography-mass spectrometry and the pharmacokinetic evaluation was carried out model-dependently. Only the extent of bioavailability was calculated model-independently. The extent of the absolute bioavailability (F) of tramadol in the suppositories, based on AUC data, was 77.0% (point estimate; n = 10) with a 95% confidence interval of 70.8-83.6% (ANOVAlog). The areas under the serum concentration curves of tramadol-HCl calculated by curve fitting (AUC), which agreed very well with the model-independently determined areas (AUC), were 2933 +/- 304 h.ng/ml (rectal) and 3775 +/- 446 h.ng/ml (i.v.) [mean +/- SD; n = 10]. Optimal curve fitting of the serum concentration data after rectal administration presupposed the existence of two absorption sites with different absorption rates and lag times. Under this premise the absorption half-lives were t1/2,ka;1 = 1.7 h (median; range: 1.1-3.1 h) and t1/2,ka;2 = 0.98 h (0.35-1.9 h), and the corresponding lag times were t0;1 = 0 h (0-0.37 h) and t0;2 = 0.66 h (0.31-3.5 h). The relative portion of the more rapidly absorbed quantity of tramadol varied between 9.2 and 50% (median: 28%). The maxima of the serum concentration curves were reached 2-6 h after rectal administration; the means of the individual maxima were 294 +/- 50 ng/ml (Cmax) and 3.3 +/- 1.3 h (tmax). There were large differences in the distribution rate between the volunteers. The means of the half-life of the slower distribution (t1/2, alpha) were 1.38 +/- 0.47 h (rectal; n = 10) and 1.78 +/- 0.63 h (i.v.; n = 7). In the terminal phase the biological half-life (t1/2, beta) was 5.7 +/- 1.0 h (rectal) and 5.7 +/- 0.9 h (i.v.), respectively. The values determined after i.v. injection for the total distribution volume and the total clearance were 216 +/- 231 (Vd, beta) and 447 +/- 56 ml/min (Cltot). The results show that after rectal administration of the tramadol suppositories the absorption of the active ingredient is rapid enough for therapeutic purposes and that the extent of the absolute bioavailability is higher than after oral administration of tramadol-HCl, probably due to a reduced first-pass metabolisation after rectal administration.
Overcoming the Heme Paradox: Heme Toxicity and Tolerance in Bacterial Pathogens (2010)

Virtually all bacterial pathogens require iron to infect vertebrates. The most abundant source of iron within vertebrates is in the form of heme as a cofactor of hemoproteins. Many bacterial pathogens have elegant systems dedicated to the acquisition of heme from host hemoproteins. Once internalized, heme is either degraded to release free iron or used intact as a cofactor in catalases, cytochromes, and other bacterial hemoproteins. Paradoxically, the high redox potential of heme makes it a liability, as heme is toxic at high concentrations. Although a variety of mechanisms have been proposed to explain heme toxicity, the mechanisms by which heme kills bacteria are not well understood. Nonetheless, bacteria employ various strategies to protect against and eliminate heme toxicity. Factors involved in heme acquisition and detoxification have been found to contribute to virulence, underscoring the physiological relevance of heme stress during pathogenesis. Herein we describe the current understanding of the mechanisms of heme toxicity and how bacterial pathogens overcome the heme paradox during infection.
Changes in the pattern of DNA methylation associate with twin discordance in systemic lupus erythematosus (2009)

Monozygotic (MZ) twins are partially concordant for most complex diseases, including autoimmune disorders. Whereas phenotypic concordance can be used to study heritability, discordance suggests the role of non-genetic factors. In autoimmune diseases, environmentally driven epigenetic changes are thought to contribute to their etiology. Here we report the first high-throughput and candidate sequence analyses of DNA methylation to investigate discordance for autoimmune disease in twins. We used a cohort of MZ twins discordant for three diseases whose clinical signs often overlap: systemic lupus erythematosus (SLE), rheumatoid arthritis, and dermatomyositis. Only MZ twins discordant for SLE featured widespread changes in the DNA methylation status of a significant number of genes. Gene ontology analysis revealed enrichment in categories associated with immune function. Individual analysis confirmed the existence of DNA methylation and expression changes in genes relevant to SLE pathogenesis. These changes occurred in parallel with a global decrease in the 5-methylcytosine content that was concomitantly accompanied with changes in DNA methylation and expression levels of ribosomal RNA genes, although no changes in repetitive sequences were found. Our findings not only identify potentially relevant DNA methylation markers for the clinical characterization of SLE patients but also support the notion that epigenetic changes may be critical in the clinical manifestations of autoimmune disease.
Anastrozole Is Superior to Tamoxifen as First-Line Therapy for Advanced Breast Cancer in Postmenopausal Women: Results of a North American Multicenter Randomized Trial (2000)

Anastrozole satisfied the predefined criteria for equivalence to tamoxifen. Furthermore, we observed both a significant increase in TTP and a lower incidence of thromboembolic events and vaginal bleeding with anastrozole. These findings indicate that anastrozole should be considered as first-line therapy for postmenopausal women with advanced breast cancer.
Endogenous Wnt Signaling Promotes Proliferation and Suppresses Osteogenic Differentiation in Human Adipose Derived Stromal Cells (2006)

Multipotential adult mesenchymal stem cells (MSC) are able to differentiate along several known lineages, and lineage commitment is tightly regulated through specific cellular mediators and interactions. Human adipose tissues contain cell populations that have similar characteristics to bone marrow stromal cells. Wnt proteins have been reported to be involved in proliferation and differentiation of stem cells. RNA interference (RNAi) has recently emerged as a specific and efficient method to silence gene expression in mammalian cells. To analyze the role of beta-catenin signaling in human adipose stromal cells (hADSC), the effects of beta-catenin short hairpin RNAs (shRNA) expression and Wnt3a conditioned media on the growth and differentiation properties of hADSC were examined. Expression of an RNAi molecule to beta-catenin from a lentivirus vector decreased beta-catenin expression in hADSC, as indicated by Western blot and immunohistochemistry. Cells transduced with sibeta-catenin lentivirus had decreased CFU and lower numbers of cells per colony than transduced control cells, but this outcome did not result from altered attachment efficiency of hADSC. The inhibition of beta-catenin signal by RNAi expression increased osteogenic differentiation. The treatment of Wnt3a conditioned media increased cellular beta-catenin levels and the rate of cellular proliferation, but inhibited osteogenic differentiation. Transduction of beta-catenin RNAi lentivirus blocked the effect of Wnt3a on proliferation of hADSC. Taken together, these findings indicate that endogenous Wnt3a plays an important role in the regulation of proliferation and differentiation of hADSC.
Porcine Reproductive and Respiratory Syndrome Virus Comparison: Divergent Evolution on Two Continents (1999)

Porcine reproductive and respiratory syndrome virus (PRRSV) is a recently described arterivirus responsible for disease in swine worldwide. Comparative sequence analysis of 3'-terminal structural genes of the single-stranded RNA viral genome revealed the presence of two genotypic classes of PRRSV, represented by the prototype North American and European strains, VR-2332 and Lelystad virus (LV), respectively. To better understand the evolution and pathogenicity of PRRSV, we obtained the 12,066-base 5'-terminal nucleotide sequence of VR-2332, encoding the viral replication activities, and compared it to those of LV and other arteriviruses. VR-2332 and LV differ markedly in the 5' leader and sections of the open reading frame (ORF) 1a region. The ORF 1b sequence was nearly colinear but varied in similarity of proteins encoded in identified regions. Furthermore, molecular and biochemical analysis of subgenomic mRNA (sgmRNA) processing revealed extensive variation in the number of sgmRNAs which may be generated during infection and in the lengths of noncoding sequence between leader-body junctions and the translation-initiating codon AUG. In addition, VR-2332 and LV select different leader-body junction sites from a pool of similar candidate sites to produce sgmRNA 7, encoding the viral nucleocapsid protein. The presence of substantial variations across the entire genome and in sgmRNA processing indicates that PRRSV has evolved independently on separate continents. The near-simultaneous global emergence of a new swine disease caused by divergently evolved viruses suggests that changes in swine husbandry and management may have contributed to the emergence of PRRS.
Multiple sclerosis and restless legs syndrome: a systematic review and meta‐analysis (2012)

This systematic review indicates that RLS prevalence amongst patients with MS ranges from 12.12% to 57.50% in different populations. Pooled analysis further indicates that the odds of RLS amongst patients with MS are fourfold higher compared to people without MS.
The alpha v beta 3 integrin associates with a 190-kDa protein that is phosphorylated on tyrosine in response to platelet-derived growth factor (1993)

Integrins are cell surface heterodimers that mediate cell adhesion to the extracellular matrix. We show that in mouse 3T3 fibroblasts the alpha v beta 3 integrin (vitronectin receptor) coprecipitates with a tyrosine-phosphorylated 190-kDa protein, as detected by antibodies to phosphotyrosine. Three different antibodies to the vitronectin receptor, all of which precipitate the alpha/beta complex, coprecipitated a 190-kDa protein. The three antibodies were raised against the purified placental vitronectin receptor, the platelet alpha IIb beta 3 integrin, and the cytoplasmic domain of the alpha v subunit. The association was specific for the vitronectin receptor, since an antibody to the alpha 5 beta 1 integrin (fibronectin receptor) did not coprecipitate any tyrosine-phosphorylated protein. The phosphorylation of the 190-kDa protein was observed only following cell activation by platelet-derived growth factor, which is known to stimulate tyrosine kinase activity and to modulate cell adhesion. Antibodies raised against the platelet-derived growth factor alpha and beta receptors (M(r) = 170,000 and 190,000, respectively) did not recognize the 190-kDa, integrin-associated phosphorylated protein. Occupancy of the vitronectin receptor by one of its ligands, vitronectin, resulted in an increased amount of tyrosine phosphorylation of the 190-kDa protein. Our data suggest that the association of tyrosine-phosphorylated proteins with integrins may play an important role in growth factor-mediated modulation of cell adhesion.
Localization of MODY3 to a 5-cM Region of Human Chromosome 12 (1995)

Maturity-onset diabetes of the young (MODY) is a heterogeneous disorder that appears to be characterized by a primary defect in insulin secretion. Mutations in an unknown locus (MODY1) on chromosome 20 and the glucokinase gene (MODY2) on chromosome 7 can cause this form of non-insulin-dependent diabetes. Recent genetic studies have identified a third locus on chromosome 12 (MODY3) that is linked to MODY in a group of French families. We have identified three families from Denmark, Germany, and the U.S. (Michigan) showing evidence of linkage with MODY3 and a family from Japan showing suggestive evidence. Analysis of key recombinants in these families localized MODY3 to a 5-cM interval between the markers D12S86 and D12S807/D12S820.
Opioid-induced Down-Regulation of RGS4 (2011)

Regulator of G protein signaling protein 4 (RGS4) acts as a GTPase accelerating protein to modulate μ- and δ- opioid receptor (MOR and DOR, respectively) signaling. In turn, exposure to MOR agonists leads to changes in RGS4 at the mRNA and/or protein level. Here we have used human neuroblastoma SH-SY5Y cells that endogenously express MOR, DOR, and RGS4 to study opioid-mediated down-regulation of RGS4. Overnight treatment of SH-SY5Y cells with the MOR agonist DAMGO or the DOR agonist DPDPE decreased RGS4 protein by ∼60% accompanied by a profound loss of opioid receptors but with no change in RGS4 mRNA. The decrease in RGS4 protein was prevented by the pretreatment with pertussis toxin or the opioid antagonist naloxone. The agonist-induced down-regulation of RGS4 proteins was completely blocked by treatment with the proteasome inhibitors MG132 or lactacystin or high concentrations of leupeptin, indicating involvement of ubiquitin-proteasome and lysosomal degradation. Polyubiquitinated RGS4 protein was observed in the presence of MG132 or the specific proteasome inhibitor lactacystin and promoted by opioid agonist. The loss of opioid receptors was not prevented by MG132, demonstrating a different degradation pathway. RGS4 is a GTPase accelerating protein for both Gα(i/o) and Gα(q) proteins. After overnight treatment with DAMGO to reduce RGS4 protein, signaling at the Gα(i/o)-coupled DOR and the Gα(q)-coupled M(3) muscarinic receptor (M(3)R) was increased but not signaling of the α(2) adrenergic receptor or bradykinin BK(2) receptor, suggesting the development of cross-talk between the DOR and M(3)R involving RGS4.