gebhart/patrepeval huggingface dataset:
Vaginal Clindamycin and Oral Metronidazole for Bacterial Vaginosis (2000)

In Brief Objective To compare the efficacy and safety of clindamycin vaginal ovules with oral metronidazole for treatment of bacterial vaginosis. Methods Women with bacterial vaginosis received either 100-mg ovules of clindamycin (intravaginally for 3 consecutive days) plus placebo capsules (orally twice daily for 7 days) or metronidazole 500 mg (two 250-mg capsules orally twice daily for 7 days) plus placebo ovules (intravaginally for 3 consecutive days). The sample was determined prospectively to provide a probability of .84 of correctly concluding that the rate of success for clindamycin is not more than 15% less than the expected 75% success rate for metronidazole. Clinical outcome was determined on the basis of vaginal fluid amine odor and clue cells. Results Of the 399 patients enrolled, 233 could be evaluated for efficacy. Of those, 77 (68.1%) of 113 patients were cured with clindamycin, compared with 80 (66.7%) of 120 who were cured with metronidazole (95% confidence interval −10.6%, 13.4%; P = .810). Treatment-related adverse events were reported more frequently in the metronidazole treatment group. Systemic symptoms, such as nausea and taste perversion, accounted for most of the difference between groups. Conclusion A 3-day regimen of clindamycin, given as intravaginal ovules, was as effective as and better tolerated than a 7-day regimen of oral metronidazole 500 mg, given twice daily, for treatment of bacterial vaginosis. Intravaginal clindamycin for 3 days and oral metronidazole for 5 days are similarly effective treatments for bacterial vaginosis, but the former is better tolerated.
Inhibition of G9a induces DUSP4-dependent autophagic cell death in head and neck squamous cell carcinoma (2014)

In this study, we provide evidence that G9a confers the survival advantage of HNSCC. Genetic or pharmacological inhibition of G9a induces autophagic cell death; this finding provides a basis for new therapeutic targets for treating HNSCC.
Major and minor discordance in the diagnosis of postmenopausal osteoporosis among Indian women using hip and spine dual-energy X-ray absorptiometry (2012)

The large prevalence of discordance may reflect the differences in osteoporosis in different populations and suggests the need to redefine ranges and risk factors used for the diagnosis of osteoporosis in India.
Mutational analysis of the ATP‐binding site in HslU, the ATPase component of HslVU protease in Escherichia coli (1996)

HslU is the ATPase component of the ATP-dependent HslVU protease in Escherichia coli. To gain an insight into the structure and function of HslU, site-directed mutagenesis was performed to generate a mutation in the ATP-binding site of the ATPase (i.e., to replace the Lys63 with Thr). Unlike the wild-type HslU, the mutant form (referred to as HslU/K63T) could not hydrolyze ATP or support the ATP-dependent hydrolysis of N-carbobenzoxy-Gly-Gly-Leu-7-amido-4-methyl coumarin by HslV. The wild-type HslU (a mixture of monomer and dimer) formed a multimer containing 6-8 subunits in the presence of either ATP or ADP, indicating that ATP-binding, but not its hydrolysis, is required for oligomerization of HslU. However, HslU/K63T remained as a monomer whether or not the adenine nucleotides were present. Furthermore, ATP or ADP could protect HslU, but not HslU/K63T, from degradation by trypsin. These results suggest that the mutation in the ATP-binding site results in prevention of the binding of the adenine nucleotides to HslU and hence in impairment of both oligomerization and ATPase function of HslU.
Astrocytic hypertrophy in dysmyelination influences the diffusion anisotropy of white matter (2007)

The effect of a proteolipid protein (PLP) mutation on the developing white matter anisotropy was examined by diffusion tensor magnetic resonance imaging (DT-MRI) in a noninvasive study of a mouse model of Pelizaeus-Merzbacher disease (PMD). The jimpy PLP mutation in mice produces an irreversible dysmyelination in jimpy males, whereas heterozygous females exhibit a transient hypomyelination, as assessed by a longitudinal study of the same mice during development. Modifications of the different individual DT-MRI parameters were highlighted by specific changes in tissue structures caused by the mutation that includes the hypomyelination, axonal abnormalities, and recovery. Astrocytic hypertrophy is a striking cellular event in dysmyelinated jimpy brain, where most axons or bundles of fibers are entirely wrapped by astrocyte cytoplasmic processes, so its influences on DT-MRI parameters in dysmyelination were examined for the first time. DT-MRI data of the jimpy brain were compared with those obtained from dysmyelination of (oligo-TTK) transgenic mice, induced by oligodendrocyte killing, which have a mild astrocyte hypertrophy (Jalabi et al., 2005), and from recovering jimpy females, which have reduced astrocyte hypertrophy. The unique morphological feature of astrocytes in jimpy males coupled with an increase in the water channel protein aquaporin 4 (AQP4) was found to facilitate the directional water diffusion in the white matter. In addition to the major changes of DT-MRI parameters in the two dysmyelinated mice caused by the myelin loss and axonal modifications, the amplified magnitude of radial and axial diffusions in jimpy males was attributed principally to the strongly pronounced astrocyte hypertrophy.
Photoperiodic Control of Melanoma Growth in Hamsters: Influence of Pinealectomy and Melatonin* (1983)

Pinealectomy (PX) increased MM1 (melanotic melanoma no. 1) hamster melanoma growth in animals held under a 14-h light, 10-h dark (14:10) photoperiod without altering tumor latency. Hamsters maintained under a 6-h light, 18-h dark (6:18) photoperiod exhibited gonadal collapse, a longer tumor latency, and slower tumor growth rate than animals held under 14:10. PX produced a further increase in tumor latency and a decrease in growth in these animals. In contrast, acute morning injection of low doses (50 micrograms/day) of melatonin or delivery by Silastic capsule (35 micrograms/day) implanted at the time of tumor cell inoculation increased MM1 melanoma growth in hamsters held under 14:10 photocycle, without affecting testicular or adrenal function. Treatment of hamsters 11 weeks before tumor cell inoculation with 14 micrograms/day melatonin via Silastic capsule produced a decrease in serum PRL but no change in tumor growth or testicular or adrenal weights in animals held under 14:10. Treatment of hamsters with 17.7 micrograms/day melatonin (Silastic capsule) 11 weeks before tumor cell inoculation increased testes and adrenal weights as well as serum PRL and androgen levels, but significantly decreased tumor growth in hamsters held under a short daily photoperiod. These results suggest that the photoperiod under which hamsters are maintained dictates the growth rate of MM1 tumors and the effect of PX on tumor behavior. When photoperiod significantly alters gonadal and adrenal function, the quantity, time, and duration of melatonin presentation are all important variables in the effect of melatonin on tumor growth.
Cover Image (2018)

The cover image is based on the Research Article A coupled immersed boundary-lattice Boltzmann method with smoothed point interpolation method for fluid-structure interaction problems, by Shuangqiang Wang et al., https://doi.org/10.1002/fld.4669.
Pomegranate Byproduct Administration to Apolipoprotein E-Deficient Mice Attenuates Atherosclerosis Development as a Result of Decreased Macrophage Oxidative Stress and Reduced Cellular Uptake of Oxidized Low-Density Lipoprotein (2006)

The effects of a pomegranate byproduct (PBP, which includes the whole pomegranate fruit left after juice preparation) on atherosclerosis development in apolipoprotein E-deficient (E degrees ) mice were studied. Consumption of PBP (17 or 51.5 microg of gallic acid equiv/kg/day) by the mice resulted in a significant reduction in atherosclerotic lesion size by up to 57%. PBP consumption significantly reduced oxidative stress in the mice peritoneal macrophages (MPM): Cellular lipid peroxide content decreased by up to 42%, the reduced glutathione levels increased by up to 53%, and paraoxonase 2 lactonase activity increased by up to 50%, as compared to MPM from E degrees mice that consumed only water. Furthermore, oxidized low-density lipoprotein (Ox-LDL) uptake by the MPM was reduced by up to 19%. Similar results were observed also in vitro. Treatment of J774A.1 macrophages with PBP (10 or 50 micromol/L of total polyphenols) significantly decreased both cellular total peroxide content and Ox-LDL uptake. It was thus concluded that PBP significantly attenuates atherosclerosis development by its antioxidant properties.
Functional Analysis of the α-1,3-Glucan Synthase Genes agsA and agsB in Aspergillus nidulans: AgsB Is the Major α-1,3-Glucan Synthase in This Fungus (2013)

Although α-1,3-glucan is one of the major cell wall polysaccharides in filamentous fungi, the physiological roles of α-1,3-glucan remain unclear. The model fungus Aspergillus nidulans possesses two α-1,3-glucan synthase (AGS) genes, agsA and agsB. For functional analysis of these genes, we constructed several mutant strains in A. nidulans: agsA disruption, agsB disruption, and double-disruption strains. We also constructed several CagsB strains in which agsB expression was controlled by the inducible alcA promoter, with or without the agsA-disrupting mutation. The agsA disruption strains did not show markedly different phenotypes from those of the wild-type strain. The agsB disruption strains formed dispersed hyphal cells under liquid culture conditions, regardless of the agsA genetic background. Dispersed hyphal cells were also observed in liquid culture of the CagsB strains when agsB expression was repressed, whereas these strains grew normally in plate culture even under the agsB-repressed conditions. Fractionation of the cell wall based on the alkali solubility of its components, quantification of sugars, and (13)C-NMR spectroscopic analysis revealed that α-1,3-glucan was the main component of the alkali-soluble fraction in the wild-type and agsA disruption strains, but almost no α-1,3-glucan was found in the alkali-soluble fraction derived from either the agsB disruption strain or the CagsB strain under the agsB-repressed conditions, regardless of the agsA genetic background. Taken together, our data demonstrate that the two AGS genes are dispensable in A. nidulans, but that AgsB is required for normal growth characteristics under liquid culture conditions and is the major AGS in this species.
Our approach to follicular-patterned lesions of the thyroid (2006)

Follicular-patterned lesions of the thyroid are common; these include hyperplastic/adenomatoid nodules, follicular adenoma, follicular carcinoma and follicular variants of papillary carcinoma. Most of these lesions can be diagnosed with ease; however, there is a controversial subgroup. In this review, we present our diagnostic approach based on our experience with the histological diagnosis of these tumours, which can help in appropriate clinical management.
Mode recoupling in a novel Bragg grating pair (2003)

A new type of mode recoupling in a Bragg grating pair, in which one of the gratings is written in the fiber cladding, is proposed to overcome limitations of concatenated long-period and fiber Bragg gratings reported earlier [Opt. Lett.27, 1214 (2002)]. Its reflection spectrum is similar to that of the previously reported concatenated grating structure; however, the reflectivity can be much larger than the previous limitation of 50%. Furthermore, avoidance of the loss induced by a long-period grating makes such a Bragg grating pair more attractive for practical applications.
An unexpected role for the anaphylatoxin C5a receptor in allergic sensitization (2006)

The anaphylatoxins complement component 3a and 5a (C3a and C5a, respectively) are classically seen as proinflammatory mediators of allergic asthma that recruit inflammatory cells, induce edema, and cause bronchoconstriction. A few years ago, controversy arose when it was shown that C5-deficient mice were more susceptible to experimental asthma compared with C5-sufficient mice. In a study by Köhl et al. in this issue of the JCI, it is shown in a series of truly "complementary" experiments that C5a receptor (C5aR) blockade promotes Th2 sensitization upon first exposure to inhaled allergen, whereas C5aR blockade during established inflammation suppresses the cardinal features of asthma (see the related article beginning on page 783). Blockade of C5aR alters the function of airway DCs, crucial for inducing and maintaining Th2 responses in the lung. Targeting C5aR as a treatment for established asthma could be beneficial, but might be accompanied by sensitization to novel antigens.
DNA repair is more important than catalase for Salmonella virulence in mice. (1995)

Pathogenic microorganisms possess antioxidant defense mechanisms for protection from reactive oxygen metabolites such as hydrogen peroxide (H2O2), which are generated during the respiratory burst of phagocytic cells. These defense mechanisms include enzymes such as catalase, which detoxify reactive oxygen species, and DNA repair systems which repair damage resulting from oxidative stress. To determine the relative importance of these two potentially protective defense mechanisms against oxidative stress encountered by Salmonella during infection of the host, a Salmonella typhimurium double mutant unable to produce either the HPI or HPII catalase was constructed, and compared with an isogenic recA mutant deficient in DNA repair. The recA mutant was hypersusceptible to H2O2 at low cell densities in vitro, while the catalase mutant was more susceptible to high H2O2 concentrations at high cell densities. The catalase mutant was found to be resistant to macrophages and retained full murine virulence, in contrast to the recA mutant which previously was shown to be macrophage-sensitive and attenuated in mice. These observations suggest that Salmonella is subjected to low concentrations of H2O2 while at relatively low cell density during infection, conditions requiring an intact DNA repair system but not functional catalase activity.
Endothelial origin of mesenchymal stem cells (2011)

Mesenchymal stem/stromal cells (MSCs) are fibroblastoid cells capable of long-term expansion and skeletogenic differentiation. While MSCs are known to originate from neural crest and mesoderm, immediate mesodermal precursors that give rise to MSCs have not been characterized. Recently, using human embryonic stem cells (hESCs), we demonstrated that mesodermal MSCs arise from APLNR+ precursors with angiogenic potential, mesenchymoangioblasts, which can be identified by FGF2-dependent colony-forming assay in serum-free semisolid medium. In this overview we provide additional insights on cellular pathways leading to MSC establishment from mesoderm, with special emphasis on endothelial-mesenchymal transition as a critical step in MSC formation. In addition, we highlight an essential role of FGF2 in induction of angiogenic cells with potential to transform into MSCs (mesenchymoangioblasts) or hematopoietic cells (hemangioblasts) from mesoderm, and discuss correlations of our in vitro findings with the course of angioblast development during embryogenesis.
Cyclooxygenase-2 Promotes Amyloid Plaque Deposition in a Mouse Model of Alzheimer's Disease Neuropathology (2002)

Several epidemiologic studies have reported that cyclooxygenase (COX) inhibitors prevent/delay the onset of Alzheimer's disease (AD). Recent experimental studies suggest that these compounds can also diminish amyloid-beta (Abeta) neuropathology in rodent models of AD. To explore the relationship of COX expression to Abeta neuropathology, we crossed mice expressing both mutant amyloid precursor protein [K670N/M671L (APP(swe)] and mutant PS1 (A246E) with mice expressing human COX-2 selectively in neurons. We show here that human COX-2 expression in APP(swe)/PS1/COX-2 mice induces potentiation of brain parenchymal amyloid plaque formation and a greater than twofold increase in prostaglandin E2 production, at 24 months of age. This increased amyloid plaque formation coincided with a preferential elevation of Abeta1-40 and Abeta1-42 with no change in total amyloid precursor protein (APP) expression/content in the brain. Collectively these data suggest that COX-2 influences APP processing and promotes amyloidosis in the brain.
Infection of Lymphoid Cells by Integration-Defective Human Immunodeficiency Virus Type 1 Increases De Novo Methylation (2001)

DNA methylation, by regulating the transcription of genes, is a major modifier of the eukaryotic genome. DNA methyltransferases (DNMTs) are responsible for both maintenance and de novo methylation. We have reported that human immunodeficiency virus type 1 (HIV-1) infection increases DNMT1 expression and de novo methylation of genes such as the gamma interferon gene in CD4(+) cells. Here, we examined the mechanism(s) by which HIV-1 infection increases the cellular capacity to methylate genes. While the RNAs and proteins of all three DNMTs (1, 3a, and 3b) were detected in Hut 78 lymphoid cells, only the expression of DNMT1 was significantly increased 3 to 5 days postinfection. This increase was observed with either wild-type HIV-1 or an integrase (IN) mutant, which renders HIV replication defective, due to the inability of the provirus to integrate into the host genome. Unintegrated viral DNA is a common feature of many retroviral infections and is thought to play a role in pathogenesis. These results indicate another mechanism by which unintegrated viral DNA affects the host. In addition to the increase in overall genomic methylation, hypermethylation and reduced expression of the p16(INK4A) gene, one of the most commonly altered genes in human cancer, were seen in cells infected with both wild-type and IN-defective HIV-1. Thus, infection of lymphoid cells with integration-defective HIV-1 can increase the methylation of CpG islands in the promoters of genes such as the p16(INK4A) gene, silencing their expression.
Three-Dimensional Structure of Escherichia coli Branched-Chain Amino Acid Aminotransferase at 2.5 Resolution (1997)

The X-ray crystallographic structure of the branched-chain amino acid aminotransferase from Escherichia coli was determined by means of isomorphous replacement using the selenomethionyl enzyme as one of the heavy atom derivatives. The enzyme is a homo hexamer with D3 symmetry, and the polypeptide chain of the subunit is folded into two domains (small and large domains). The coenzyme, pyridoxal 5'-phosphate, resides at the domain interface, its re-face facing toward the protein. The active site structure shows that the following sites can recognize branched-chain amino acids and glutamate as substrates: (1) a hydrophobic core formed by Phe36, Tyr164, Tyr31*, and Val109* for a branched-chain; (2) Arg97 for an acidic side chain of glutamate; and (3) Tyr95 and two main chain NH groups of Thr257 and Ala258 for the alpha-carboxylate of substrates. Although the main chain conformation of the active site is homologous to that of D-amino acid aminotransferase, many of the active site residues are different between them.
Orthopaedic applications for PLA‐PGA biodegradable polymers (1998)

Biodegradable polymers, especially those belonging to the family of polylactic acid (PLA) and polyglycolic acid (PGA), play an increasingly important role in orthopaedics. These polymers degrade by hydrolysis and enzymatic activity and have a range of mechanical and physical properties that can be engineered appropriately to suit a particular application. Their degradation characteristics depend on several parameters including their molecular structure, crystallinity, and copolymer ratio. These biomaterials are also rapidly gaining recognition in the fledging field of tissue engineering because they can be fashioned into porous scaffolds or carriers of cells, extracellular matrix components, and bioactive agents. Although their future appears to be bright, several questions regarding the biocompatibility of these materials linger and should be addressed before their wide-scale use. In the context of musculoskeletal tissue, this report provides a comprehensive review of properties and applications of biodegradable PLA/PGA polymers and their copolymers. Of special interest are orthopaedic applications, biocompatibility studies, and issues of sterilization and storage of these versatile biomaterials. Also discussed is the fact that terms such as PLA, PGA, or PLA-PGA do not denote one material, but rather a large family of materials that have a wide range of differing bioengineering properties and concomitant biological responses. An analysis of some misconceptions, problems, and potential solutions is also provided.
Influence of organic solvent mixtures on biological membranes. (1985)

A simple experimental model was used to study the influence of organic solvents and solvent mixtures on the integrity of biological membranes. Radiolabelled membranes were prepared biosynthetically by growing Escherichia coli in the presence of 14C-oleic acid; the bulk of the radioactivity was incorporated into 14C-phosphatidylethanolamine, the predominant phospholipid species in E coli membranes. The radiolabelled bacteria were incubated at 37 degrees C in the presence of solvent, and the mixture filtrated through a Millipore 0.45 micron filter. This filtration retained radiolabel associated with the bacteria, and only radiolabel released as a result of solvent action was allowed through the filter. The radioactivity in the filtrate was then counted and expressed as a percentage of the total radioactivity. Results showed that aliphatic alcohols released membrane constituents in relation to their hydrocarbon chain length (1-propanol greater than 2-propanol greater than ethanol greater than methanol); the effects of aliphatic alcohols were potentiated by acetone, ethyl methyl ketone, ethylene glycol, and N,N'-dimethylformamide, and the effects of ethanol were potentiated by 1-butanol, benzyl alcohol, and ethylacetate. These findings point to the possibility that certain mixtures of organic solvents are more damaging to membranes than the components of the mixture would indicate, and suggest that the experimental model used might help in showing mixtures that are particularly harmful.
Human transcription factor YY1 represses human immunodeficiency virus type 1 transcription and virion production (1994)

The transcriptional activity of human immunodeficiency virus type 1 (HIV-1) is affected by many cellular factors. Homologies near the HIV-1 initiator region to the DNA-binding sequences of YY1, a multifunctional transcription factor known to regulate diverse viral and cellular promoters, suggested that YY1 might regulate HIV-1. Antibody to YY1 blocked the formation of complexes by HeLa cell nuclear extract and a DNA oligonucleotide encoding the HIV-1 initiator region. HIV-1 long terminal repeat (LTR) expression, as measured the expression of a transfected LTR-CAT reporter gene, was repressed more than 12-fold by the cotransfection of a YY1 expression vector. HIV-1 production by both COS-1 and CEM cells after transfection of an infectious molecular HIV-1 clone was repressed 7- to 20-fold by cotransfection of a YY1 expression vector. HIV-1 production was also decreased threefold in a CD4-positive lymphocyte cell line chronically infected with HIV-1 (8E5) after transfection of YY1. In situ hybridization studies confirmed that YY1 reduced HIV-1 RNA expression. YY1 may play an important role in the regulation of HIV-1 LTR expression in vivo and virus production by infected cells.