gebhart/patrepeval huggingface dataset:
Homogeneous Scoring of Single-Nucleotide Polymorphisms: Comparison of the 5′-Nuclease TaqMan ® Assay and Molecular Beacon Probes (2000)

Homogeneous assays based on real-time fluorescence monitoring during PCR are relevant alternatives for large-scale genotyping of single-nucleotide polymorphisms (SNPs). We compared the performance of the homogeneous TaqMan 5'-nuclease assay and the Molecular Beacon assay using three SNPs in the human estrogen receptor gene as targets. When analyzing a panel of 90 DNA samples, both assays yielded a comparable power of discrimination between the genotypes of a C-to-T transition in codon 10 and a G-to-A transition in codon 594 of the estrogen receptor gene. The Molecular Beacon probes distinguished better than the TaqMan probes between homozygous and heterozygous genotypes of a C-to-G transversion in codon 325. The sensitivity of detecting one allele, present as a minority in a mixed sample, varied between the SNPs and was similar for both assays. With the Molecular Beacon assay, the measured signal ratios were proportional to the amount of the minor allele over a wider range than with the TaqMan assay at all three SNPs.
Prevention of Plaque Rupture: A New Paradigm of Therapy (2002)

Acute coronary syndromes--unstable angina, myocardial infarction, and sudden cardiac death--are caused by acute disruption of an unstable coronary atheroma. Unstable plaques have three histologic characteristics: a large lipid core, many inflammatory cells, and a thin fibrous cap. Because the unstable plaque is not necessarily obstructive, it may cause no symptoms before rupture. The cellular processes that lead to the characteristic histologic features of unstable plaque have recently been identified. This new understanding of the cell biology of plaque instability suggests new therapeutic strategies: passivation of the endothelium, reduction of low-density lipoprotein (LDL) in the vessel wall by decreasing serum LDL levels or accelerating reverse cholesterol transport, inhibition of LDL oxidation, inhibition of inflammatory cytokine expression, and inhibition of thrombus formation. Although the morbidity and mortality resulting from acute coronary disease have been reduced by more than 50% over the past 30 years, it is reasonable to anticipate further reductions of similar magnitude in the decade ahead.
Vasopressin Antagonists: Role in the Management of Hyponatremia (2006)

Hyponatremia is a common electrolyte disorder associated with potentially serious or life-threatening consequences. Serum osmolality and sodium concentration [Na+] are regulated by thirst, the hormone arginine vasopressin (AVP), and renal water and sodium handling. Hyponatremia is frequently caused by dysregulation of AVP, which accompanies disorders of water retention, such as congestive heart failure (CHF) and the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). Clinical trials with AVP receptor antagonists have confirmed the important role of AVP in the pathophysiology of hyponatremia and suggest these agents are efficacious in treating hyponatremia associated with SIADH, cirrhosis, and CHF. Acting directly at AVP receptors in the renal tubules, these agents promote aquaresis - the electrolyte-sparing excretion of free water - in patients with hyponatremia. In clinical trials, AVP receptor antagonists have been shown to increase the serum [Na+] and urine output while decreasing urine osmolality.
Antisense-mediated suppression of human heparanase gene expression inhibits pleural dissemination of human cancer cells. (2001)

Heparan sulfate proteoglycans is a major component of the cell surface and extracellular matrix and functions as a barrier against cationic molecules and macromolecules. Heparanase is an endoglucuronidase capable of specifically degrading heparan sulfate, and its activity is associated with the metastatic potential of tumor cells. To inhibit human heparanase expression in human cancer cells, we constructed an adenoviral vector carrying a full-length human heparanase cDNA in an antisense orientation (Ad-AS/hep). Increased heparanase expression in T.Tn human esophageal cancer cells and A549 human lung cancer cells after infection with an adenovirus vector expressing the human heparanase gene (Ad-S/hep) was specifically inhibited by simultaneous infection with Ad-AS/hep in a dose-dependent manner. A modified Boyden chamber assay demonstrated that infection with Ad-AS/hep significantly inhibited in vitro invasion of A549 cells after Ad-S/hep infection. Moreover, intrathoracic administration of Ad-AS/hep reduced the number and size of heparanase-expressing A549 tumors implanted intrathoracically into BALB/c-nu/nu mice. Our results suggest that heparanase contributes to the invasive phenotype of tumor cells, and that antisense-mediated inhibition of heparanase activity may be efficacious in the prevention of pleural dissemination.
Evidence for Cardiomyopathy in Familial Diabetes Mellitus (1977)

A C T Recent epidemiologic studies have suggested that cardiac disease is common in diabetics and may often have a noncoronary basis. To examine the status of the left ventricle, 17 adult-onset diabetics of familial type without hypertension or obesity under- went hemodynamic study and were compared to 9 controls of similar age.
New Effect Size Rules of Thumb (2009)

Recommendations to expand Cohen’s (1988) rules of thumb for interpreting effect sizes are given to include very small, very large, and huge effect sizes. The reasons for the expansion, and implications for designing Monte Carlo studies, are discussed.
Protected environment and its utility in experimental allogeneic and xenogeneic bone marrow transplantation. (1985)

Allogeneic bone marrow (BM) chimerism can be established in germfree (GF) rats and mice without the manifestations of graft vs host (GvH) disease that develop in conventional counterpart animals. This procedure has been applied with prophylactic and therapeutic benefits in mice predestined to develop leukemia and reticulum cell sarcoma. Xenogeneic BM chimerism has been accomplished in rats with mouse bone marrow cells, without evidence of GvH disease; and over long periods they produce blood cells with characteristics of mouse species. A critical factor in allogeneic and xenogeneic BM chimerism is the microbial status of the animals.
Antimalarial effects of vinyl sulfone cysteine proteinase inhibitors (1996)

We evaluated the antimalarial effects of vinyl sulfone cysteine proteinase inhibitors. A number of vinyl sulfones strongly inhibited falcipain, a Plasmodium falciparum cysteine proteinase that is a critical hemoglobinase. In studies of cultured parasites, nanomolar concentrations of three vinyl sulfones inhibited parasite hemoglobin degradation, metabolic activity, and development. The antimalarial effects correlated with the inhibition of falcipain. Our results suggest that vinyl sulfones or related cysteine proteinase inhibitors may have promise as antimalarial agents.
Genetic basis of respiratory distress syndrome (2006)

Respiratory distress syndrome (RDS) is a multifactorial developmental disease caused by lung immaturity and presenting as high-permeability lung edema ("hyaline membrane disease"). It is characterized by a transient deficiency of alveolar surfactant during the first week of life. During the first few days of life, the alveolar surfactant pool size increases up to that in the controls. The allelic variants of the genes encoding the surfactant proteins (SP) SP-A1, SP-A2, SP-B, and SP-C have been associated with RDS. The main SP-A haplotype, interactively with the SP-B Ile131Thr polymorphism and with constitutional and environmental factors, influence the risk. Case reports on mutations with partially functional SP-B have been published. The genetic susceptibility factors depend on the degree of prematurity at birth, consistent with sequential differentiation of the lung and gestation-dependent differences in clinical presentation. The preferentially type 2 cell expressed genes involved in critical functions (such as ATP-binding cassette transporter, ABCA3), those involved in susceptibility to acute lung damage, and those with known susceptibility to other severe lung diseases (such as G protein-coupled receptor for asthma susceptibility, GPR154 alias GPRA) will possibly serve as candidate genes in future studies. RDS associated with near-term and term births may have a different genetic predisposition and pathogenesis compared to RDS after very preterm birth. As we learn more about the molecular consequences of allelic variation, new therapies based on a new generation of surfactant diagnostics and individualized therapies may follow.
Ileal J pouch: radiologic evaluation in patients with and without postoperative infectious complications. (1990)

The authors studied the ileograms and computed tomographic (CT) examinations of 18 patients who had undergone surgical construction of an ileal J pouch and ileoanal anastomosis; 10 had developed postoperative infectious complications and eight had not. The initial ileograms obtained 4 weeks postoperatively proved to be unhelpful in predicting future infectious complications, showing abnormalities in only two of 10 patients. Ileography and CT performed at the time of the complications showed abnormalities in eight of nine and nine of 10 patients, respectively. Ileographic abnormalities in patients with abscesses included extravasation of contrast material, extraluminal gas collections, thickening of ileal pouch folds, and extrinsic mass effect on the pouch. CT findings included thickening of the pouch and/or rectal walls, streaky areas of soft-tissue attenuation within the ileal pouch mesentery and perirectal fat, and areas of soft-tissue attenuation or fluid attenuation in the peripouch region. CT was more valuable in depicting the site and extent of abscess formation before surgical or percutaneous drainage.
Immunohistochemical detection of the androgen receptor with monoclonal antibody F39.4 in routinely processed, paraffin-embedded human tissues after microwave pre-treatment. (1994)

We describe the immunohistochemical detection of the human androgen receptor (AR) in routinely processed, paraffin-embedded tissue with the monoclonal antibody (MAb) F39.4. Deparaffinized sections were heated in a microwave oven for antigen retrieval. A panel of human male- and female-derived tissues was investigated. We observed a nuclear staining pattern consistent with previous results on frozen sections. Moreover, we studied the possibility of detecting AR in prolonged formalin-fixed tissue and in paraffin-embedded archival material. After prolonged fixation times or long-term storage of paraffin-embedded tissue, the staining intensity for the AR did not deteriorate. Blocking experiments with the specific synthetic peptides demonstrated the specificity of this technique. We conclude that this method is specific, allows retrospective AR studies, and offers optimally preserved morphology.
Increased prokineticin 2 expression in gut inflammation: role in visceral pain and intestinal ion transport (2011)

Elevated Prok2 levels, as a consequence of gastrointestinal tract inflammation, induce visceral pain via prokineticin receptors. This observation, together with the finding that PROK2 can modulate intestinal ion transport, raises the possibility that inhibitors of PROK2 signaling may have clinical utility in gastrointestinal disorders, such as irritable bowel syndrome and inflammatory bowel disease.
Neuromodulation and the Urinary Tract—Are We Over the Rainbow or Have We Simply Stepped Through the Looking Glass? (2007)

No AccessJournal of UrologyEditorial1 Nov 2007Neuromodulation and the Urinary Tract—Are We Over the Rainbow or Have We Simply Stepped Through the Looking Glass?is accompanied byAldose Reductase Inhibitor ONO-2235 Restores the Alterations of Bladder Nerve Growth Factor and Neurotrophin Receptor p75 Genetic Expression in Streptozotocin Induced Diabetic Ratsis companion ofTranscutaneous Mechanical Nerve Stimulation Using Perineal Vibration: A Novel Method for the Treatment of Female Stress Urinary IncontinenceResults of Sacral Neuromodulation Therapy for Urinary Voiding Dysfunction: Outcomes of a Prospective, Worldwide Clinical Study Roger Dmochowski Roger DmochowskiRoger Dmochowski More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2007.08.062AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "Neuromodulation and the Urinary Tract—Are We Over the Rainbow or Have We Simply Stepped Through the Looking Glass?." The Journal of Urology, 178(5), pp. 1844–1845 Department of Urology, Vanderbilt University School of Medicine, Nashville, Tennessee© 2007 by American Urological AssociationFiguresReferencesRelatedDetailsRelated articlesJournal of Urology17 Sep 2007Aldose Reductase Inhibitor ONO-2235 Restores the Alterations of Bladder Nerve Growth Factor and Neurotrophin Receptor p75 Genetic Expression in Streptozotocin Induced Diabetic RatsJournal of Urology17 Sep 2007Transcutaneous Mechanical Nerve Stimulation Using Perineal Vibration: A Novel Method for the Treatment of Female Stress Urinary IncontinenceJournal of Urology17 Sep 2007Results of Sacral Neuromodulation Therapy for Urinary Voiding Dysfunction: Outcomes of a Prospective, Worldwide Clinical Study Volume 178Issue 5November 2007Page: 1844-1845 Advertisement Copyright & Permissions© 2007 by American Urological AssociationMetricsAuthor Information Roger Dmochowski More articles by this author Expand All Advertisement PDF downloadLoading ...
Testis-specific transcription start site in the aspartate aminotransferase housekeeping gene promoter. (1994)

We have studied the expression and regulation of the rat testis cytosolic aspartate aminotransferase gene. The cytosolic aspartate aminotransferase activity was 5-fold lower in the testis than in the liver and kidney. A 1.9-kilobase mRNA form was detected in the rat testis in contrast to the 2.1- and 1.8-kilobase forms present in other organs. Using Northern blot and S1 mapping analyses, we found that the proximal polyadenylation site was almost exclusively used in the testis as opposed to other organs where the distal site was preferentially used. RNase protection and primer extension analysis showed that transcription was initiated at multiple sites in all organs, but the pattern of those start sites was different in the testis; in particular, a novel transcription start site was specifically detected in this organ (at position -115 from the translation start site). This site was first observed in 29-day-old rats and was maximally utilized in the adult testis. DNase I footprinting using testis nuclear extracts revealed the presence of three sites of DNA-protein interaction in the 250-base pair proximal promoter, a pattern similar to the one found using liver nuclear extracts. However, the proteins bound had different properties as shown by gel retardation experiments. We conclude that the pattern of transcription initiation and the polyadenylation site selection of a housekeeping gene can be tissue-specific.
The novel monoclonal antibody 9F5 reveals expression of a fragment of GPNMB/osteoactivin processed by furin‐like protease(s) in a subpopulation of microglia in neonatal rat brain (2016)

To differentiate subtypes of microglia (MG), we developed a novel monoclonal antibody, 9F5, against one subtype (type 1) of rat primary MG. The 9F5 showed high selectivity for this cell type in Western blot and immunocytochemical analyses and no cross-reaction with rat peritoneal macrophages (Mφ). We identified the antigen molecule for 9F5: the 50- to 70-kDa fragments of rat glycoprotein nonmetastatic melanoma protein B (GPNMB)/osteoactivin, which started at Lys(170) . In addition, 9F5 immunoreactivity with GPNMB depended on the activity of furin-like protease(s). More important, rat type 1 MG expressed the GPNMB fragments, but type 2 MG and Mφ did not, although all these cells expressed mRNA and the full-length protein for GPNMB. These results suggest that 9F5 reactivity with MG depends greatly on cleavage of GPNMB and that type 1 MG, in contrast to type 2 MG and Mφ, may have furin-like protease(s) for GPNMB cleavage. In neonatal rat brain, amoeboid 9F5+ MG were observed in specific brain areas including forebrain subventricular zone, corpus callosum, and retina. Double-immunοstaining with 9F5 antibody and anti-Iba1 antibody, which reacts with MG throughout the CNS, revealed that 9F5+ MG were a portion of Iba1+ MG, suggesting that MG subtype(s) exist in vivo. We propose that 9F5 is a useful tool to discriminate between rat type 1 MG and other subtypes of MG/Mφ and to reveal the role of the GPNMB fragments during developing brain. GLIA 2016;64:1938-1961.
RNA-targeted splice-correction therapy for neuromuscular disease (2010)

Splice-modulation therapy, whereby molecular manipulation of premessenger RNA splicing is engineered to yield genetic correction, is a promising novel therapy for genetic diseases of muscle and nerve-the prototypical example being Duchenne muscular dystrophy. Duchenne muscular dystrophy is the most common childhood genetic disease, affecting one in 3500 newborn boys, causing progressive muscle weakness, heart and respiratory failure and premature death. No cure exists for this disease and a number of promising new molecular therapies are being intensively studied. Duchenne muscular dystrophy arises due to mutations that disrupt the open-reading-frame in the DMD gene leading to the absence of the essential muscle protein dystrophin. Of all novel molecular interventions currently being investigated for Duchenne muscular dystrophy, perhaps the most promising method aiming to restore dystrophin expression to diseased cells is known as 'exon skipping' or splice-modulation, whereby antisense oligonucleotides eliminate the deleterious effects of DMD mutations by modulating dystrophin pre-messenger RNA splicing, such that functional dystrophin protein is produced. Recently this method was shown to be promising and safe in clinical trials both in The Netherlands and the UK. These trials studied direct antisense oligonucleotide injections into single peripheral lower limb muscles, whereas a viable therapy will need antisense oligonucleotides to be delivered systemically to all muscles, most critically to the heart, and ultimately to all other affected tissues including brain. There has also been considerable progress in understanding how such splice-correction methods could be applied to the treatment of related neuromuscular diseases, including spinal muscular atrophy and myotonic dystrophy, where defects of splicing or alternative splicing are closely related to the disease mechanism.
Vorticity organization in the outer layer of turbulent channels with disturbed walls (2007)

The vortex clusters in the turbulent outer region of rough- and smooth-walled channels, and their associated velocity structures, are compared using data from numerical experiments at friction Reynolds numbers Re τ ≤ 674. The results indicate that the roughness of the wall does not affect their properties, particularly the existence of wall-detached and wall-attached populations, and the self-similar size distribution of the latter. The average flow field conditioned to the attached clusters reveals similar conical structures of low streamwise velocity for the rough- and smooth-walled cases, which eventually grow into the global modes previously identified from spectral analysis. We conclude that the vortex clusters of the turbulent outer region either originate away from the wall, or quickly forget their origin, in agreement with Townsend's similarity hypothesis.
[Expression of Candida antarctica lipase B on yeast surface and synthesis of ethyl hexanoate catalyzed by CALB]. (2008)

Short-chain esters play a significant role in the food industry as flavor and aroma constituents. Candida antarctica lipase B (CALB) is one of the most effective catalysts for organic synthesis. We constructed a CALB-displaying yeast whole-cell biocatalyst and applied it to esterification from caproic acid and ethanol. CALB was fused with the alpha-agglutinin C-terminal and the signal peptide of Glucoamylase in pICAS, a yeast surface display vector, to construct plasmid pICAS-CALB. An extremely Asn-rich linker, named celAL was inserted in the Xho I of pICAS-CALB to construct plasmid pICAS-celAL-CALB. The fused gene was under the control of GAPDH promoter. After incubated at 30 degrees C for 96 h the lipase hydrolytic activity of the yeast whole cells reached a plateau, 26.26 u/(g x dry cell). In nonaqeous media, the yield of 98.0% ethyl hexanoate was obtained after 24 h esterification from caproic acid and ethanol (the molar ratio of caproic acid : ethanol = 1 : 1.25) using lyophilized CALB displaying yeast whole cells.
MicroRNAs miR-26a, miR-26b, and miR-29b accelerate osteogenic differentiation of unrestricted somatic stem cells from human cord blood (2013)

miR-26a/b and miR-29b are upregulated during osteogenic differentiation of USSC and share target genes inhibiting osteogenesis. Furthermore, these microRNAs accelerate osteogenic differentiation, likely mediated by osteo-inhibitory proteins such as CDK6 and HDAC4.
Novel plasma kallikrein inhibitors of the benzamidine type. (1994)

Besides guanidino compounds and amines structurally related to arginine and lysine, compounds with an amidino moiety are inhibitors of trypsin-like enzymes. However, in most cases ordinary benzamidine derivatives are not selective inhibitors. Relatively selective inhibitors of some enzymes were found among amino acids containing a benzamidine moiety at the side chain. For example, derivatives of phenyl-alpha-aminobutyric acid with one or two amidino moieties such as the 4'-amidinoanilide of N alpha-[4-amidinophenylsulfonyl]-phenyl-alpha- aminobutyric acid are potent and selective inhibitors of plasma kallikrein (Ki = 0.15 microM). Using N alpha-arylsulfonylated 3-amidinophenylalanine as the key building block, novel inhibitors of plasma kallikrein were developed. Several esters and amides of the nipecotic acid derivative were synthesized which inhibit plasma kallikrein competitively with Ki values between 0.1 and 1.0 microM. The compounds prolonged aPTT in micromolar concentration, indicating an inhibition of the intrinsic coagulation pathway.
Effect of prolonged low-dose angiotensin II infusion on the sensitivity of adrenal cortex in man. (1975)

The effect of incremental infusions of isoleucine-5-angiotensin II on blood pressure and plasma aldosterone concentrations was studied in normal man before and after 66 hours of intravenous infusion of angiotensin II at 2 ng kg-1 min-1, sodium and potassium balance being kept roughly constant throughout. Plasma sodium and ACTH concentrations were unaltered, but plasma potassium and magnesium levels and basal plasma cortisol fell slightly after prolonged angiotensin administration. During the prolonged angiotensin infusion plasma renin activity was suppressed, and there was a sustained elevation of arterial pressure and plasma aldosterone concentration. Aldosterone excretion, while clearly increased, showed a regular circadian rhythm, with peak values in the early morning. The angiotensin II-pressor relationship was not significantly changed after the prolonged infusion of angiotensin II, while the angiotensin II-aldosterone dose-response curve was steeper than in the basal state but not identical with that of sodium depletion. No differences were observed in the pressor or aldosterone-stimulant effects of the isoleucine-5 and valine-5 forms of angiotensin II. A trophic effect of angiotensin II on the adrenal cortex may provide a partial explanation for the enhanced response of aldosterone to angiotensin II in sodium depleted man.