gebhart/patrepeval huggingface dataset:
Molecular Markers for Quantitative and Discrete COPD Phenotypes (2007)

To identify gene expression markers for chronic obstructive pulmonary disease (COPD), we performed genome‐wide expression profiling of lung tissue from 56 patients with a solitary pulmonary nodule undergoing surgical resection. Analysis of differential expression between cases (FEV1&lt;70% predicted, FEV1/FVC&lt;0.7) and controls (FEV1&gt;80% predicted, FEV1/FVC&gt;0.7) identified a set of 65 transcripts representing discrete markers associated with COPD. Correlation of gene expression with a quantitative measure of airflow obstruction (FEV1), using both Pearson and Spearman coefficients (p&lt;0.01), identified a set of 65 marker transcripts. A total of 43 transcripts were identified that showed evidence of significant correlation (p&lt;0.05) with quantitative traits and differential expression between cases and controls. Finally, we used this group of disease markers to develop a gene expression signature for COPD capable of predicting disease in a previously published data set generated from patients with severe emphysema undergoing lung volume reduction surgery (Spira et. al., AJRCMB. 2004). Although these data sets represent distinct populations of COPD patients, we identified a molecular signature comprising 15 probe sets representing 8 genes (CIRBP, ZNF207, ARHGEF12, CTSK, ZF, CROP, ARHGAP29, HPGD) capable of 94% predictive accuracy. Our data contribute to the understanding of gene expression changes occurring in the lung tissue of patients with obstructive lung disease and provide additional insight into potential mechanisms involved in the disease process. Funded by NHLBI
The RTX haemolysins ApxI and ApxII are major virulence factors of the swine pathogenActinobacillus pleuropneumoniae:evidence from mutational analysis (1994)

The involvement of the RTX haemolysins (ApxI and ApxII) of the swine pathogen Actinobacillus pleuropneumoniae in virulence was investigated using haemolysin-deficient mutants constructed by a mini-Tn10 mutagenesis procedure. Two types of haemolysin mutant with single insertions of the transposon were obtained from a serotype 1 strain producing both ApxI and ApxII. One presented a complete loss of haemolytic activity because of the absence of ApxI and ApxII production. The other displayed weaker haemolysis than the wild type and produced only ApxII. The chromosomal regions flanking mini-Tn10 were cloned and sequenced. In the non-haemolytic mutant, the transposon had inserted in apxIB, a gene involved in the exportation of ApxI and ApxII toxins. The weakly haemolytic mutant resulted from the disruption of the structural gene for ApxI. Both mutations in the apxI operon were associated with a significant loss of virulence for mice and pigs, demonstrating that haemolysins are involved in A. pleuropneumoniae pathogenicity. The non-haemolytic mutant was apathogenic and the weakly haemolytic mutant retained some virulence for pigs, suggesting that both ApxI and ApxII are needed for full virulence.
The cytotoxic protein YopE of Yersinia obstructs the primary host defence (1990)

It has previously been shown that the plasmid-encoded YopE protein of Yersinia pseudotuberculosis is a virulence determinant. In this study, HeLa cells, macrophages and mice were used as different model systems to determine the actual role of YopE in the virulence process. The YopE protein mediates a cytotoxic response on a confluent layer of HeLa cells. A prerequisite of this activity is that the pathogen binds to the cell surface. YopE also induces a cytotoxic response on mouse macrophages where it influences the ability of the pathogen to resist phagocytosis. Bacterial mutants defective in their ability to express YopE are avirulent after oral or intraperitoneal infection but virulent following intravenous injection. On the basis of these results, we propose a role for YopE in the virulence process of Yersinia.
Modulating an oxidative-inflammatory cascade: potential new treatment strategy for improving glucose metabolism, insulin resistance, and vascular function (2008)

Type 2 diabetes is a result of derangement of homeostatic systems of metabolic control and immune defense. Increases in visceral fat and organ adipose, environmental factors and genetic predisposition create imbalances of these homeostatic mechanisms, ultimately leading to a condition in which the oxidative environment cannot be held in check. A significant imbalance between the production of reactive oxygen species and antioxidant defenses, a condition called to oxidative stress, ensues, leading to alterations in stress-signalling pathways and potentially end-organ damage. Oxidative stress and metabolic inflammation upregulate the expression pro-inflammatory cytokines, including tissue necrosis factor alpha, monocyte chemoattractant protein-1 and interleukin-6, as well as activating stress-sensitive kinases, such as c-Jun N-terminal kinase (JNK), phosphokinase C isoforms, mitogen-activated protein kinase and inhibitor of kappa B kinase. The JNK pathway (specifically JNK-1) appears to be a regulator that triggers the oxidative-inflammation cascade that, if left unchecked, can become chronic and cause abnormal glucose metabolism. This can lead to insulin resistance and dysfunction of the vasculature and pancreatic beta-cell. The series of events set in motion by the interaction between metabolic inflammation and oxidative stress constitutes an 'oxidative-inflammatory cascade', a delicate balance driven by mediators of the immune and metabolic systems, maintained through a positive feedback loop. Modulating an oxidative-inflammation cascade may improve glucose metabolism, insulin resistance and vascular function, thereby slowing the development and progression to cardiovascular diseases and type 2 diabetes.
A single amino acid substitution in sigma E affects its ability to bind core RNA polymerase (1995)

We have examined the role of the most highly conserved region of bacterial RNA polymerase sigma factors by analyzing the effect of amino acid substitutions and small deletions in sigma E from Bacillus subtilis. sigma E is required for the production of endospores in B. subtilis but not for vegetative growth. Strains expressing each of several mutant forms of sigE were found to be deficient in their ability to form endospores. Single amino acid substitutions at positions 68 and 94 resulted in sigma factors that bind with less affinity to the core subunits of RNA polymerase. The substitution at position 68 did not affect the stability of the protein in B. subtilis; therefore, this substitution probably did not have large effects on the overall structure of the sigma factor. The substitution at position 68 probably defines a position in sigma E that closely contacts a subunit of RNA polymerase, while the substitution at position 94 may define a position that is important for protein stability or for binding to core RNA polymerase.
Localization of messenger RNA for Mr 72,000 and 92,000 type IV collagenases in human skin cancers by in situ hybridization. (1992)

We have examined the expression of 2 type IV collagen degrading enzymes (Mr 72,000 and 92,000 type IV collagenases) in human skin cancer by in situ hybridization. In all cases of infiltrating carcinomas of squamous cell (9 of 9) and basal cell (5 of 5) types, messenger RNA for the Mr 72,000 type IV collagenase was present in numerous fibroblasts. These were especially abundant in the stroma adjacent to the invasive tumor nodules. Malignant cells were negative for mRNA for the Mr 72,000 enzyme in all cases as were all other epithelial as well as endothelial cells. mRNA for the Mr 92,000 type IV collagenase was present in all 9 squamous cell and in 3 of the 5 basal cell carcinomas. In all these cases, a subpopulation of tissue macrophages was found to be positive, while malignant cells showed a signal for Mr 92,000 type IV collagenase in 6 of the squamous cell carcinomas but in none of the basal cell carcinomas. In all cases, the signal for this mRNA was confined to cells located at the tumoral/stromal interface or in the close vicinity of tumor nodules. No mRNA for any of the 2 collagenases was detected in 3 biopsies of normal skin. In vitro studies have indicated that collagenases are involved in the degradation of the extracellular matrix during cancer invasion. The present findings are consistent with such a role of the Mr 72,000 and 92,000 type IV collagenases in squamous and basal cell carcinomas in situ. The findings also demonstrate that degradative enzymes are not necessarily produced by the malignant cells themselves but may be generated by induction or recruitment of nonmalignant stromal cells.
Synthetic listeners and synthetic performers (1990)

Each partner in a collaborative music performance must also be an expert listener. Several “performers” have been built for a variety of musical situations, and each given a listening skill that permits it to substitute for a human performer. This typically entails real-time pitch detection of an instrument or voice, matching the events heard against an encoded score, then adding its own part in synchronization. Necessary skills include ultra-sensitivity to changes of tempo, and the ability to improve by learning from rehersals. This has worked for a broad class of performance situations: Baroque flute/harpsichord, 20th century violin/piano, and some jazz standards—in all cases, music that can be known from a score or by acoustic repetition. Some attention has also been given to how humans first negotiate unfamiliar acoustic territory, such as perceiving rhythmic structure in a piece not heard before. A real-time auditory model of rhythmic perception and cognition (running on a desktop machine with audio I/O) suggests that the neuronal processing involved in foot-tapping to unfamiliar music may be relatively inexpensive as human tasks go.
Molecular structure of the IL‐3, GM‐CSF and IL‐5 receptors (1992)

Reconstitution of high-affinity receptors using molecularly cloned receptor subunits has revealed that the high-affinity receptors for interleukin 3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF) and IL-5 are composed of two distinct subunits alpha and beta. Both subunits are members of the cytokine receptor superfamily that have the common structural motif in their extracellular domains. The alpha subunits are cytokine-specific, and each alpha subunit binds its specific ligand with low affinity. The human has a common beta subunit that does not bind any cytokine by itself but forms high-affinity receptors for GM-CSF, IL-3 and IL-5 with the respective alpha subunit. Therefore, cross-competition of binding between these cytokines occurs by competition for the common beta subunit between different alpha subunits in the human. In contrast, the mouse has two distinct beta subunits; one is specific for the IL-3 receptor, and the other is equivalent to the human common beta subunit. The beta subunits are not only required for high-affinity binding to ligands, but they are also essential for signal transduction. The high-affinity receptors induce protein tyrosine phosphorylation and activate the ras protein. However, neither alpha nor beta subunit has an intrinsic protein kinase, indicating that additional components are necessary for signal transduction.
The Genetic Basis of Cancer of the Kidney (2003)

Kidney cancer used to be considered a single disease. It is now known that there are a number of different types of cancers of the kidney with different histological patterns and different clinical courses that appear to respond differently to therapy. These different types of kidney cancer are caused by different genes, ie they each have a distinct genetic basis. Understanding the molecular pathways of these cancer genes should provide insight into their varying clinical courses and responses to treatment as well as provide the foundation for the development of disease specific molecular therapeutic strategies.
Gene polymorphisms in glyphosate‐resistant and ‐susceptible biotypes of Eleusine indica from Malaysia (2003)

Summary Resistant (R) and susceptible (S) biotypes of Eleusine indica were collected from four areas, namely Chaah, Lenggeng, Bidor and Temerloh, in Malaysia. Restriction fragment length polymorphism (RFLP) and polymerase chain reaction (PCR)‐RFLP analyses using Sph I restriction enzyme were able to differentiate the R biotype from the S biotype by showing R‐specific and S‐specific polymorphisms in E. indica from three of the areas, with the exception of Temerloh where no polymorphisms were detected. The different DNA profiles for the R biotypes obtained indicate that Sph I is not a useful diagnostic marker. The DNA polymorphisms detected in the 5‐enolpyruvylshikimate 3‐phosphate (EPSP) synthase gene suggest that there are different mutation events leading to development of resistance to glyphosate. Partial sequencing of the EPSP synthase gene confirmed different mutations occurring with substitution of proline with serine or threonine at amino acid 106 for the R biotype in Chaah, Bidor and Temerloh.
VASOACTIVE NATRIURETIC PEPTIDES AND KIDNEY (1998)

Summary. The natriuretic peptide family (ANP, BNP, CNP) is responsible for the body fluid homeostasis and blood pressure control. ANP and BNP act on guanylate cyclase-A and CNP on guanylate cyclase-B receptors.The main renal actions of ANP are: 1. direct and indirect effects on the kidney to alter renal hemodynamics, and to increase fluid and electrolyte excretion; 2. functional antagonism of the renin-angiotensin-aldosterone system (R-A-A) by inhibiting synthesis and/or relase of renin and aldosterone, and by antagonising all known effects of angiotensin. ANP increases single nephron GFR in proportion of total GFR due mainly to an increase in glomerular capillary hydrostatic pressure that results from efferent arteriolar constriction and afferent arteriolar dilation. ANP indirectly acts on tubular sites that are targets of R-A-A system, including proximal tubular sites (angiotensin) and distal nephron sites (aldosteron). Regulation of CNP secretion is different from that of ANP and BNP, which are cardiac hormones. The increase of the plasma CNP in chronic renal failure (CNF) can be due to the diminished clearance of CNP in the kidney or due to increase in CNP production that occurs in the renal parenchymal cells. In chronic renal failure (CRF) exists a downregulation of ANP clearance receptors due to exaggerated ANP-stimulated cGMP response in CRF glomeruli. In hemodialysis patients, changes in plasma ANP are greater than in BNP and more responsive to changes in left atrial volume due to ultrafiltration.
HLA class I antigen and transporter associated with antigen processing (TAP1 and TAP2) down-regulation in high-grade primary breast carcinoma lesions. (1998)

Five specimens of normal mammary tissue and 53 primary breast carcinoma lesions were tested for expression of HLA antigens and components of the antigen-processing machinery by immunohistochemical staining. The expression of transporter associated with antigen processing (TAP) 1, TAP2, and HLA class I antigens in breast carcinoma lesions was significantly associated with tumor grading. Like normal mammary tissue, the 16 low-grade (G1) breast carcinoma lesions showed strong staining for TAP1, TAP2, and HLA class I antigens. In contrast, only 12 (32%) of 37 high-grade (G2 and G3) breast carcinoma lesions displayed the normal staining pattern. In 14 (38%) of 37 high-grade lesions, HLA class I antigen down-regulation was observed without loss of low molecular mass polypeptide and/or TAP staining. Congruent down-regulation of HLA class I antigen and TAP1 or TAP2 was found in 8 (22%) of 37 high-grade lesions. Complete loss of HLA class I antigens, TAP1, and TAP2 was observed in 3 (8%) of 37 high-grade lesions. No lesion was negative for TAP1 and/or TAP2 staining while positive for HLA class I antigen staining. These data demonstrate an association of HLA class I antigen and TAP down-regulation with tumor progression in breast carcinoma. This association suggests that loss of HLA and/or TAP may represent an escape from the host's immune pressure or may reflect the accumulation of abnormalities associated with neoplastic progression. This accumulation of defects in antigen processing and presentation may in turn be responsible for reduced recognition of malignant cells by putative clinically relevant tumor-specific T cells.
Involvement of the Silencer and UAS Binding Protein RAP1 in Regulation of Telomere Length (1990)

The yeast protein RAP1, initially described as a transcriptional regulator, binds in vitro to sequences found in a number of seemingly unrelated genomic loci. These include the silencers at the transcriptionally repressed mating-type genes, the promoters of many genes important for cell growth, and the poly[(cytosine)1-3 adenine] [poly(C1-3A)] repeats of telomeres. Because RAP1 binds in vitro to the poly(C1-3A) repeats of telomeres, it has been suggested that RAP1 may be involved in telomere function in vivo. In order to test this hypothesis, the telomere tract lengths of yeast strains that contained conditionally lethal (ts) rap1 mutations were analyzed. Several rap1ts alleles reduced telomere length in a temperature-dependent manner. In addition, plasmids that contain small, synthetic telomeres with intact or mutant RAP1 binding sites were tested for their ability to function as substrates for poly(C1-3A) addition in vivo. Mutations in the RAP1 binding sites reduced the efficiency of the addition reaction.
The Irritable Bowel Syndrome: Review and a Graduated Multicomponent Treatment Approach (1992)

The irritable bowel syndrome is a common chronic disorder having a broad clinical spectrum of severity. Although only a small proportion of those afflicted seek medical help for their symptoms, a subset have severe and intractable symptoms. A positive diagnosis should be established from the history and physical examination; endoscopic and radiologic investigations should be minimized. We suggest that the physician also assess the severity of the illness based on its symptomatic and functional features and the patient's behavioral response. Classifying the disorder in this manner permits a graduated treatment approach that emphasizes education, reassurance, and dietary adjustment for mild symptoms. Moderate symptom severity requires, in addition, identification and modification of factors exacerbating symptoms, psychotherapeutic and behavioral techniques and, if a certain symptom type predominates, pharmacologic agents directed toward the presumed gastrointestinal motor dysfunction. For severe symptoms, physician-based behavior modification and psychopharmacologic agents are helpful. When the disorder is intractable, referral may be needed, for example, to a pain treatment center. In all cases, the skillful physician must ensure continued psychosocial support to enhance coping and continued focus on the palliative aspects of care rather than on cure.
Binding of lysozyme to lipopolysaccharide suppresses tumor necrosis factor production in vivo (1994)

Endotoxin (lipopolysaccharide [LPS]) released during gram-negative bacterial infection induces varieties of cytokines which directly and/or indirectly cause shock, disseminated intravascular coagulation, and death. We previously showed that lysozyme (LZM) was an LPS-binding protein and inhibited various immunomodulating activities of LPS. In this study, we examined the effect of LZM on the LPS-triggered septic shock model induced by carrageenan treatment and assessed by tumor necrosis factor production. The data presented in this report strongly suggest that LZM-LPS complex formation completely abrogates tumor necrosis factor production and the mortality caused by LPS and that LZM may be useful for the treatment of endotoxin shock.
Flow cytometric differentiation of erythrocytes and leukocytes in dilute whole blood by light scattering (1998)

We have determined differential scattering cross sections of sphered erythrocytes integrated over the solid angle accepted by our detectors at wavelengths varying between 379.5-632.8 nm, employing Ar+-, Kr+-, and HeNe-laser radiation. Integrated differential cross sections for forward and orthogonal light scatter exhibit a pronounced minimum at about lambda = 413 nm, caused by the strong absorption of light by oxyhemoglobin. Experimental data are in good agreement with values calculated by the Mie theory. Simultaneous measurements of forward and orthogonal light scatter using Kr+-laser radiation (lambda = 413.1 nm) allow flow cytometric differentiation of (native) erythrocytes, thrombocytes, and leukocytes as well as subpopulations of leukocytes, i.e., granulocytes, lymphocytes, and monocytes in dilute whole-blood samples. Lysis of red blood cells or staining of white blood cells is not required to obtain absolute leukocyte counts or differential white blood cell counts.
Bone Morphogenetic Protein-9 Is a Circulating Vascular Quiescence Factor (2008)

Angiogenesis is a complex process, requiring a finely tuned balance between numerous stimulatory and inhibitory signals. ALK1 (activin receptor like-kinase 1) is an endothelial-specific type 1 receptor of the transforming growth factor-beta receptor family. Heterozygotes with mutations in the ALK1 gene develop hereditary hemorrhagic telangiectasia type 2 (HHT2). Recently, we reported that bone morphogenetic protein (BMP)9 and BMP10 are specific ligands for ALK1 that potently inhibit microvascular endothelial cell migration and growth. These data lead us to suggest that these factors may play a role in the control of vascular quiescence. To test this hypothesis, we checked their presence in human serum. We found that human serum induced Smad1/5 phosphorylation. To identify the active factor, we tested neutralizing antibodies against BMP members and found that only the anti-BMP9 inhibited serum-induced Smad1/5 phosphorylation. The concentration of circulating BMP9 was found to vary between 2 and 12 ng/mL in sera and plasma from healthy humans, a value well above its EC(50) (50 pg/mL). These data indicated that BMP9 is circulating at a biologically active concentration. We then tested the effects of BMP9 in 2 in vivo angiogenic assays. We found that BMP9 strongly inhibited sprouting angiogenesis in the mouse sponge angiogenesis assay and that BMP9 could inhibit blood circulation in the chicken chorioallantoic membrane assay. Taken together, our results demonstrate that BMP9, circulating under a biologically active form, is a potent antiangiogenic factor that is likely to play a physiological role in the control of adult blood vessel quiescence.