gebhart/patrepeval huggingface dataset:
Acute Antibody-Mediated Complement Activation Mediates Lysis of Pancreatic Islets Cells and May Cause Tissue Loss in Clinical Islet Transplantation (2008)

The conclusion is that complement is activated by natural IgG and IgM antibodies already after 5 min. The complement activation leads to lysis of cells of the pancreatic islets. This very rapid reaction may be an essential entity of the damage induced by the IBMIR in clinical islet transplantation.
Mitochondrial Phospholipid Hydroperoxide Glutathione Peroxidase Plays a Major Role in Preventing Oxidative Injury to Cells (1999)

Phospholipid hydroperoxide glutathione peroxidase (PHGPx) is synthesized as a long form (L-form; 23 kDa) and a short form (S-form; 20 kDa). The L-form contains a leader sequence that is required for transport to mitochondria, whereas the S-form lacks the leader sequence. A construct encoding the leader sequence of PHGPx tagged with green fluorescent protein was used to transfect RBL-2H3 cells, and the fusion protein was transported to mitochondria. The L-form of PHGPx was identified as the mitochondrial form of PHGPx and the S-form as the non-mitochondrial form of PHGPx since preferential enrichment of mitochondria for PHGPx was detected in M15 cells that overexpressed the L-form of PHGPx, whereas no similar enrichment was detected in L9 cells that overexpressed the S-form. Cell death caused by mitochondrial injury due to potassium cyanide (KCN) or rotenone (chemical hypoxia) was considerably suppressed in the M15 cells, whereas the L9 cells and control RBL-2H3 cells (S1 cells, transfected with the vector alone) succumbed to the cytotoxic effects of KCN. Flow cytometric analysis showed that mitochondrial PHGPx suppressed the generation of hydroperoxide, the loss of mitochondrial membrane potential, and the loss of plasma membrane integrity that are induced by KCN. Mitochondrial PHGPx might prevent changes in mitochondrial functions and cell death by reducing intracellular hydroperoxides. Mitochondrial PHGPx failed to protect M15 cells from mitochondrial injury by carbonyl cyanide m-chlorophenylhydrazone, which directly reduces membrane potential without the generation of hydroperoxides. M15 cells were more resistant than L9 cells to cell death caused by direct damage to mitochondria and to extracellular oxidative stress. L9 cells were more resistant to tert-butylhydroperoxide than S1 cells, whereas resistance to t-butylhydroperoxide was even more pronounced in M15 cells than in L9 cells. These results suggest that mitochondria might be a target for intracellular and extracellular oxidative stress and that mitochondrial PHGPx, as distinct form non-mitochondrial PHGPx, might play a primary role in protecting cells from oxidative stress.
Graphene geometric diodes for terahertz rectennas (2013)

We demonstrate a new thin-film graphene diode called a geometric diode that relies on geometric asymmetry to provide rectification at 28 THz. The geometric diode is coupled to an optical antenna to form a rectenna that rectifies incoming radiation. This is the first reported graphene-based antenna-coupled diode working at 28 THz, and potentially at optical frequencies. The planar structure of the geometric diode provides a low RC time constant, on the order of 10−15 s, required for operation at optical frequencies, and a low impedance for efficient power transfer from the antenna. Fabricated geometric diodes show asymmetric current–voltage characteristics consistent with Monte Carlo simulations for the devices. Rectennas employing the geometric diode coupled to metal and graphene antennas rectify 10.6 µm radiation, corresponding to an operating frequency of 28 THz. The graphene bowtie antenna is the first demonstrated functional antenna made using graphene. Its response indicates that graphene is a suitable terahertz resonator material. Applications for this terahertz diode include terahertz-wave and optical detection, ultra-high-speed electronics and optical power conversion.
Antigen-Induced Eosinophilic Lung Inflammation Develops in Mice Deficient in Chemokine Eotaxin (1998)

The mechanisms that regulate the selective infiltration of eosinophils in certain allergic diseases are still poorly understood. The CC chemokine eotaxin is a potent chemoattractant, highly specific for eosinophils. Recent studies have implicated that eotaxin plays an important role in the recruitment of eosinophils in different inflammation processes. A number of other chemokines, cytokines, and chemoattractants also have chemotactic activities for eosinophils and some of them present high selectivity for eosinophils. To further study the role of eotaxin in inflammation, we generated mutant mice with the eotaxin gene disrupted and replaced by the Escherichia coliβ-galactosidase gene. These mice developed normally and had no histologic or hematopoietic abnormalities. Furthermore, our studies showed that the lack of eotaxin did not affect the recruitment of eosinophils in the inflammation models induced by Sephadex beads and thioglycollate, as well as in an experimental lung eosinophilia model induced by ovalbumin aerosol challenge, even at the onset of the inflammatory response. The replacement of the eotaxin gene by the β-galactosidase gene provided a useful marker to monitor the activity of the eotaxin promoter under normal conditions and after antigen challenges. Immunohistochemical staining suggested that endothelial cells were the major sources of eotaxin expression.
YKL-40 and mesothelin in the blood of patients with malignant mesothelioma, lung cancer and asbestosis. (2013)

The addition of YKL-40 may improve the specificity of mesothelin measurements alone for detecting patients with MM.
The transcriptional regulation of miR-21, its multiple transcripts and their implication in prostate cancer (2010)

MicroRNAs (miRNAs) are a natural part of the most recently discovered and global regulatory pathway known as RNA interference. Functional studies have shown how specific miRNAs can function as tumor suppressors or oncogenes and, correspondingly, deregulated miRNA profiles have been observed in prostate and other cancers. However, the upstream pathways which regulate miRNA expression are only currently being uncovered. The Androgen Receptor (AR) is a nuclear hormone receptor and transcription factor which plays a paramount role in prostate cancer (PCa) pathobiology. We performed high throughput miRNA microarray analysis on two AR-responsive cell lines to identified 16 candidate AR-regulated miRNAs.(1) One of the most androgen-induced candidates was a known oncogenic miRNA, miR-21. In a small study of early grade PCa samples we found that miR-21 levels were frequently elevated in comparison to adjacent normal tissue. This observation was supported in the literature(2,3) and suggests clinical relevance. We found that the activated AR directly interacts with miR-21 regulatory regions, indicating direct transcriptional induction. Furthermore, we provide new reporter studies supporting AR-regulation. Importantly, in functional studies, we found that a modest overexpression of miR-21 enhanced tumor xenograft growth and was sufficient to support androgen-independent proliferation following surgical castration. Thus, our studies suggest a model where miR-21 contributes to androgen-dependent and androgen-independent PCa growth. However, the AR is only one of many reported transcriptional regulators of miR-21. Here we review our recent discoveries and further analyze the reported miR-21 regulatory regions, inhibitory and stimulatory signaling pathways, and primary transcripts.
Ullrich scleroatonic muscular dystrophy is caused by recessive mutations in collagen type VI (2001)

Ullrich syndrome is a recessive congenital muscular dystrophy affecting connective tissue and muscle. The molecular basis is unknown. Reverse transcription-PCR amplification performed on RNA extracted from fibroblasts or muscle of three Ullrich patients followed by heteroduplex analysis displayed heteroduplexes in one of the three genes coding for collagen type VI (COL6). In patient A, we detected a homozygous insertion of a C leading to a premature termination codon in the triple-helical domain of COL6A2 mRNA. Both healthy consanguineous parents were carriers. In patient B, we found a deletion of 28 nucleotides because of an A --> G substitution at nucleotide -2 of intron 17 causing the activation of a cryptic acceptor site inside exon 18. The second mutation was an exon skipping because of a G --> A substitution at nucleotide -1 of intron 23. Both mutations are present in an affected brother. The first mutation is also present in the healthy mother, whereas the second mutation is carried by their healthy father. In patient C, we found only one mutation so far-the same deletion of 28 nucleotides found in patient B. In this case, it was a de novo mutation, as it is absent in her parents. mRNA and protein analysis of patient B showed very low amounts of COL6A2 mRNA and of COL6. A near total absence of COL6 was demonstrated by immunofluorescence in fibroblasts and muscle. Our results demonstrate that Ullrich syndrome is caused by recessive mutations leading to a severe reduction of COL6.
MicroRNA in Cervical Cancer: OncomiRs and Tumor Suppressor miRs in Diagnosis and Treatment (2014)

Cervical cancer is a female-specific disease with a high incidence and mortality. MicroRNAs (miRNAs) are implicated in posttranscriptional regulation of gene expression and in the pathogenic mechanisms of cancer, suggesting their importance in diagnosis and treatment. miRNAs may have roles in the pathogenesis of cervical cancer based on the increases or decreases in several specific miRNAs found in patients with this disease. The miRNAs implicated in cervical cancer are miR-21, miR-126, and miR-143, and clinical application of these miRNAs for diagnosis and treatment is under investigation. Methods for diagnosis of cervical cancer include analysis of changes in the levels of specific miRNAs in serum and determination of aberrant hypermethylation of miRNAs. Supplementation of miR-143 or inhibition of miR-21 activity in vivo may be therapeutic strategy for cervical cancer. Previous approaches to development of siRNA as a drug have provided information for establishment of therapy based on these approaches, and an anti-miR-21 inhibitor has been developed. miRNAs also have effects on drug resistance and may be useful in combination therapy with other drugs.
Diacetyl : identification and characterisation of molecular mechanisms for reduction in yeast and their application in a novel enzyme based assay for quantification in fermentation systems (2006)

Diacetyl (2,3-butanedione) is an important flavour active, oxidative compound that has significant impact on cellular health as well as financial impact in industrial fermentations. The presence of diacetyl in certain fermented beverages, such as beer, results in an unpleasant butterscotch-like flavour and its concentration needs to be reduced by yeast to below the taste threshold prior to filtration and packaging. This results in significant process inefficiency. Furthermore, diacetyl negatively impacts cellular health and has been associated with neurodegenerative diseases and general cell aging amongst others. The reduction of this compound is therefore essential for cellular health.
Voice Activity and Participation Profile (2001)

Traditional clinical voice evaluation focuses primarily on the severity of voice impairment, with little emphasis on the impact of voice disorders on the individual's quality of life. This study reports the development of a 28-item assessment tool that evaluates the perception of voice problem, activity limitation, and participation restriction using the International Classification of Impairments, Disabilities and Handicaps-2 Beta-1 concept (World Health Organization, 1997). The questionnaire was administered to 40 subjects with dysphonia and 40 control subjects with normal voices. Results showed that the dysphonic group reported significantly more severe voice problems, limitation in daily voice activities, and restricted participation in these activities than the control group. The study also showed that the perception of a voice problem by the dysphonic subjects correlated positively with the perception of limitation in voice activities and restricted participation. However, the self-perceived voice problem had little correlation with the degree of voice-quality impairment measured acoustically and perceptually by speech pathologists. The data also showed that the aggregate scores of activity limitation and participation restriction were positively correlated, and the extent of activity limitation and participation restriction was similar in all except the job area. These findings highlight the importance of identifying and quantifying the impact of dysphonia on the individual's quality of life in the clinical management of voice disorders.
Immunobead-PCR: a technique for the detection of circulating tumor cells using immunomagnetic beads and the polymerase chain reaction. (1993)

The presence of tumor cells in the circulation may predict disease recurrence and metastases. We have developed a sensitive technique for the detection of carcinoma cells in blood, using immunomagnetic beads to enrich for epithelial cells and the polymerase chain reaction to identify a tumor marker. The colon carcinoma cell line SW480, homozygous for a K-ras codon 12 mutation, was used to establish optimal conditions. The SW480 cells were serially diluted in normal blood and incubated with immunomagnetic beads labeled with a monoclonal antibody specific for epithelial cells. Cells bound to the beads were retrieved using a magnetic field and the presence of K-ras codon 12 mutations determined by a polymerase chain reaction based analysis. SW480 cells could be detected in dilutions up to 1 SW480 cell/10(5) leukocytes in whole blood.
Chemokines and Cancer (1999)

Chemokines and Cancer synthesizes a state-of-the-art understanding of the role that chemokines and their receptors play in the pathophysiology of malignancy. It examines the influence of chemokines on
Comparative Efficacy of Recombinant Modified Vaccinia Virus Ankara Expressing Simian Immunodeficiency Virus (SIV) Gag-Pol and/or Env in Macaques Challenged with Pathogenic SIV (2000)

Prior studies demonstrated that immunization of macaques with simian immunodeficiency virus (SIV) Gag-Pol and Env recombinants of the attenuated poxvirus modified vaccinia virus Ankara (MVA) provided protection from high levels of viremia and AIDS following challenge with a pathogenic strain of SIV (V. M. Hirsch et al., J. Virol. 70:3741-3752, 1996). This MVA-SIV recombinant expressed relatively low levels of the Gag-Pol portion of the vaccine. To optimize protection, second-generation recombinant MVAs that expressed high levels of either Gag-Pol (MVA-gag-pol) or Env (MVA-env), alone or in combination (MVA-gag-pol-env), were generated. A cohort of 24 macaques was immunized with recombinant or nonrecombinant MVA (four groups of six animals) and was challenged with 50 times the dose at which 50% of macaques are infected with uncloned pathogenic SIVsmE660. Although all animals became infected postchallenge, plasma viremia was significantly reduced in animals that received the MVA-SIV recombinant vaccines as compared with animals that received nonrecombinant MVA (P = 0.0011 by repeated-measures analysis of variance). The differences in the degree of virus suppression achieved by the three MVA-SIV vaccines were not significant. Most importantly, the reduction in levels of viremia resulted in a significant increase in median (P < 0.05 by Student's t test) and cumulative (P = 0.010 by log rank test) survival. These results suggest that recombinant MVA has considerable potential as a vaccine vector for human AIDS.
Seeing Is Believing (2010)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Engaging men in counselling: issues for female therapists (2000)

Are men really 'difficult' in therapy or have they been largely misunderstood, especially by female therapists? That is the question [the authors] address in this timely essay. (editor abstract)
Levobetaxolol (Betaxon™) and Other β -Adrenergic Antagonists: Preclinical Pharmacology, IOP-Lowering Activity and Sites of Action in Human Eyes (2001)

The pharmacological characteristics of levobetaxolol, a single active isomer of betaxolol, were determined and compared with activities of other beta-adrenoceptor antagonists. Levobetaxolol (43-fold beta1-selective) exhibited a higher affinity at cloned human beta1 (Ki = 0.76 nM) than at beta2 (Ki = 32.6 nM) receptors, while dextrobetaxolol was much weaker at both receptors. Levobetaxolol potently antagonized functional activities at cloned human beta1 and beta2 receptors, and also at guinea pig atrial beta1, tracheal beta2 and rat colonic beta3 receptors (IC50s = 33.2 nM, 2970 nM and 709 nM, respectively). Thus, levobetaxolol was 89-times beta1-selective (vs beta2). Levobetaxolol (Ki = 16.4 nM) was more potent than dextrobetaxolol (Ki = 2.97 microM) at inhibiting isoproterenol-induced cAMP production in human non-pigmented ciliary epithelial cells. Levobunolol and (l)-timolol had high affinities at beta1 and beta2 receptors but were considerably less beta1-selective than levobetaxolol. Levo-, dextro- and racemic-betaxolol exhibited little or no affinity, except at sigma sites and Ca2+-channels (IC50s > 1 microM), at 89 other receptor/ligand binding sites. Levobetaxolol exhibited a micromolar affinity for L-type Ca2+-channels. In conscious ocular hypertensive cynomolgus monkeys, levobetaxolol was more potent than dextrobetaxolol, reducing intraocular pressure by 25.9+/-3.2% at a dose of 150 microg/eye (n = 15-30). Quantitative [3H]-levobetaxolol autoradiography revealed high levels of binding to human ciliary processes, iris, choroid/retina, and ciliary muscles. In conclusion, levobetaxolol is a potent, high affinity and beta1-selective IOP-lowering beta-adrenoceptor antagonist.
Analysis of Mucolipidosis II/III GNPTAB Missense Mutations Identifies Domains of UDP-GlcNAc:lysosomal Enzyme GlcNAc-1-phosphotransferase Involved in Catalytic Function and Lysosomal Enzyme Recognition (2014)

UDP-GlcNAc:lysosomal enzyme GlcNAc-1-phosphotransferase tags newly synthesized lysosomal enzymes with mannose 6-phosphate recognition markers, which are required for their targeting to the endolysosomal system. GNPTAB encodes the α and β subunits of GlcNAc-1-phosphotransferase, and mutations in this gene cause the lysosomal storage disorders mucolipidosis II and III αβ. Prior investigation of missense mutations in GNPTAB uncovered amino acids in the N-terminal region and within the DMAP domain involved in Golgi retention of GlcNAc-1-phosphotransferase and its ability to specifically recognize lysosomal hydrolases, respectively. Here, we undertook a comprehensive analysis of the remaining missense mutations in GNPTAB reported in mucolipidosis II and III αβ patients using cell- and zebrafish-based approaches. We show that the Stealth domain harbors the catalytic site, as some mutations in these regions greatly impaired the activity of the enzyme without affecting its Golgi localization and proteolytic processing. We also demonstrate a role for the Notch repeat 1 in lysosomal hydrolase recognition, as missense mutations in conserved cysteine residues in this domain do not affect the catalytic activity but impair mannose phosphorylation of certain lysosomal hydrolases. Rescue experiments using mRNA bearing Notch repeat 1 mutations in GNPTAB-deficient zebrafish revealed selective effects on hydrolase recognition that differ from the DMAP mutation. Finally, the mutant R587P, located in the spacer between Notch 2 and DMAP, was partially rescued by overexpression of the γ subunit, suggesting a role for this region in γ subunit binding. These studies provide new insight into the functions of the different domains of the α and β subunits.
Polyadenylation-dependent screening assay for respiratory syncytial virus RNA transcriptase activity and identification of an inhibitor (2004)

RNA-dependent RNA polymerase from respiratory syncytial virus (RSV) is a multi-subunit ribonucleoprotein (RNP) complex that, in addition to synthesizing the full 15 222 nt viral genomic RNA, is able to synthesize all 10 viral mRNAs. We have prepared crude RNP from RSV-infected HEp-2 cells, based on a method previously used for Newcastle disease virus, and established a novel polyadenylation-dependent capture [poly(A) capture] assay to screen for potential inhibitors of RSV transcriptase activity. In this homogeneous assay, radiolabeled full-length polyadenylated mRNAs produced by the viral RNP are detected through capture on immobilized biotinylated oligo(dT) in a 96-well streptavidin-coated FlashPlate. Possible inhibitors identified with this assay could interfere at any step required for the production of complete RSV mRNAs, including transcription, polyadenylation and, potentially, co-transcriptional guanylylation. A specific inhibitor of RSV transcriptase with antiviral activity was identified through screening of this assay.
Vascular Smooth Muscle Progenitor Cells (2011)

Molecular pathways that control the specification, migration, and number of available smooth muscle progenitor cells play key roles in determining blood vessel size and structure, capacity for tissue repair, and progression of age-related disorders. Defects in these pathways produce malformations of developing blood vessels, depletion of smooth muscle progenitor cell pools for vessel wall maintenance and repair, and aberrant activation of alternative differentiation pathways in vascular disease. A better understanding of the molecular mechanisms that uniquely specify and maintain vascular smooth muscle cell precursors is essential if we are to use advances in stem and progenitor cell biology and somatic cell reprogramming for applications directed to the vessel wall.