gebhart/patrepeval huggingface dataset:
Combined losartan and nitro-oleic acid remarkably improves diabetic nephropathy in mice (2013)

Diabetic nephropathy (DN) is a leading cause of end-stage renal disease (ESRD). The inhibitors of renin-angiotensin-aldosterone system (RAAS) can alleviate some of the symptoms of DN but fail to stop the progression to ESRD. Our previous studies demonstrate renoprotective action of nitro-oleic acid (OA-NO2) in several rodent models of renal disease. Here we examined the therapeutic potential and the underlying mechanism of combination of losartan and OA-NO2 in db/db mice. OA-NO2 was infused at 5 mg·kg(-1)·day(-1) via osmotic minipump, and losartan was incorporated into diet at 10 mg·kg(-1)·day(-1), each administered alone or in combination for 2 wk. Diabetic db/db mice developed progressive albuminuria and glomerulosclerosis, accompanied by podocytes loss, increased indexes of renal fibrosis, oxidative stress, and inflammation. Treatment of the diabetic mice with OA-NO2 or losartan alone moderately ameliorated kidney injury; however, the combined treatment remarkably reduced albuminuria, restored glomerular filtration barrier structure, and attenuated glomerulosclerosis, accompanied with significant suppression of renal oxidative stress and inflammation. These data demonstrate that combination of losartan and OA-NO2 effectively reverses renal injury in DN.
A Defined, Feeder-Free, Serum-Free System to Generate In Vitro Hematopoietic Progenitors and Differentiated Blood Cells from hESCs and hiPSCs (2011)

Human ESC and iPSC are an attractive source of cells of high quantity and purity to be used to elucidate early human development processes, for drug discovery, and in clinical cell therapy applications. To efficiently differentiate pluripotent cells into a pure population of hematopoietic progenitors we have developed a new 2-dimensional, defined and highly efficient protocol that avoids the use of feeder cells, serum or embryoid body formation. Here we showed that a single matrix protein in combination with growth factors and a hypoxic environment is sufficient to generate from pluripotent cells hematopoietic progenitors capable of differentiating further in mature cell types of different lineages of the blood system. We tested the differentiation method using hESCs and 9 iPSC lines generated from different tissues. These data indicate the robustness of the protocol providing a valuable tool for the generation of clinical-grade hematopoietic cells from pluripotent cells.
A comparison of the abilities of freshwater algae and bacteria to acquire and retain phosphorus1 (1984)

Extant physiological and in situ data provide contradictory answers to the question of whether the bacterioplankton can outcompete the phytoplankton for phosphorus at natural concentrations. Two phytoplankton species and three bacterial species isolated from the epilimnion of Lake Memphremagog, Québec, were grown in phosphorus‐limited continuous cultures and their abilities to take up and retain phosphorus compared. The algae showed orthophosphate uptake kinetics comparable to those reported elsewhere. In contrast, the specific orthophosphate uptake rates (i.e. uptake per unit cell P) by the bacteria were variable, but much higher than the algal rates at the low P concentrations characteristic of natural waters. Algal and bacterial alkaline phosphatase activities were similar and provided no evidence that the algae could utilize organic P more efficiently than the bacteria. The bacteria showed some tendency to excrete P more readily than the algae but mixed culture experiments indicated that excretion did little to alter the long term partitioning of phosphorus between the algae and the bacteria. The kinetic data suggest that planktonic bacteria are unlikely to be limited by phosphorus in situ. Furthermore, our results are consistent with the hypothesis that the bacteria should be markedly superior competitors at natural phosphate concentrations.
Vascular Abnormalities in Acute Reflex Sympathetic Dystrophy (CRPS I) (1999)

Demonstrated for the first time is a complete functional loss of cutaneous sympathetic vasoconstrictor activity in an early stage of RSD/CRPS I with recovery. The origin of this autonomic dysfunction is in the central nervous system.
Propagation of plant viruses in hairy root cultures: A potential method for in vitro production of epitope vaccines and foreign proteins (2006)

Hairy roots were used as an in vitro culture system for the propagation of wild-type and transgenic plant viruses. Tobacco mosaic virus (TMV) was added to the liquid culture medium at the same time as root inoculation. Hairy root growth was unaffected by viral infection. Maximum concentrations of TMV in Nicotiana benthamiana hairy roots were 1-2 orders of magnitude greater than in suspended N. benthamiana cells and reached levels of 1-2 mg g(-1) dry weight or 20-28% total soluble protein. Virus accumulated in the roots initially with a constant doubling time of about 1.0 day; subsequent reductions in viral growth rate were correlated with a significant decline in infectivity relative to the inoculum virus. The morphological integrity of the viral particles was maintained during propagation in hairy roots. The contribution to the overall viral titer of passive association of virus with the biomass, for example, by surface adsorption, was negligible compared with active viral replication. N. benthamiana hairy roots were also infected with a TMV-based viral vector developed to express green fluorescent protein (GFP). This vector was about 260-fold less infectious than wild-type TMV and accumulated much more slowly in the roots. Maximum levels of TMV-GFP in the biomass were about 65-fold lower than for TMV. This work demonstrates that hairy root cultures are a feasible means for in vitro propagation of wild-type and transgenic plant viruses under conditions that allow a high degree of environmental containment and control.
Micellar improvement of the calmagite compleximetric measurement of magnesium in plasma. (1982)

Magnesium in plasma is determined by diluting a 50-microL sample with 5.0 mL of stable calmagite reagent containing the amphoteric detergent Empigen BB, and buffered with 2-amino-2-methyl-1-propanol at pH 11.5. The calcium response is masked with strontium-buffered [ethylene-bis(oxyethylenenitrilo)]tetraacetate (EGTA), while iron is masked with triethanolamine. The detergent causes an increased separation of the test and blank spectral absorbance bands. The test absorbance peaks, which may be measured immediately, are at 520 nm, while the blank peak shifts from 610 to 655 nm on addition of detergent. The blank absorbance at 520 nm is relatively decreased by the detergent. This allows the use of a more concentrated calmagite reagent, which in turn extends the linear relation of absorbance to magnesium concentration to 5 mmol/L in plasma. This method (y) has been compared with atomic absorption procedure (x) of McDonald and Watson (Clin, Chim. Acta 14: 233, 1966) and gives favorable regression statistics (y = 1.001X + 0.057 mmol/L).
Histopathologic features of phorbol myristate acetate-induced lung injury. (1985)

Rabbits given daily intravenous injections of phorbol myristate acetate (PMA) develop acute and chronic pulmonary disease. We distinguished three phases in the histologic progression of the lung injury. An acute phase (occurring within 1.5 hours of the first injection) involved hemorrhagic pneumonitis, increased lung weight, and increased numbers of neutrophils as well as erythrocytes in alveolar fluid. The intermediate phase (occurring 1 to 7 days after the initial injection) involved interstitial pneumonitis: neutrophils and macrophages infiltrated into lung interstitium and alveolar fluid. The relative number of type II alveolar epithelial cells increased dramatically and lung weight became maximal during this phase. In the chronic phase (occurring within 14 days and lasting greater than 77 days) diffuse interstitial fibrosis progressed, whereas inflammatory changes abated. Animals treated daily with PMA developed a linear increase in lung hydroxyproline content beginning on the 7th day of treatment. Values increased to three to four times above controls by day 77. Animals treated with PMA for only 14 days and sacrificed up to 63 days thereafter had lung hydroxyproline values that were intermediate between controls and animals injected daily for 77 days. Their fibrosis neither progressed nor reversed when PMA treatment was stopped. In contrast, animals receiving a single dose of PMA developed only the acute and intermediate phases of injury; no detectable fibrosis occurred, and their lung reactions resolved completely. Finally, animals made neutropenic with nitrogen mustard did not respond to PMA with increased lung weight or changes in alveolar lavage fluid cellularity during the early or intermediate phases of the disease. They did, however, exhibit increased interstitial cellularity. Thus, PMA produces abrupt pneumonitis that progresses to fibrosis. The acute and intermediate phases of injury are neutrophil dependent and reversible, whereas the chronic fibrotic phase is irreversible and requires continued PMA injections for progression.
Vehicle selection for nonclinical oral safety studies (2013)

The rapid identification of a suitable nonclinical oral formulation is a critical step in small-molecule drug development. In order to maintain flexibility and address the needs of a diverse set of new chemical entities (NCEs) with widely varying physiochemical properties, a "tool belt" of multiple oral formulations is recommended. The appropriate formulation is identified based on the goals of the study, as well as exposure required, species, duration and therapeutic indication of the NCE.
Fundamental studies of breast tumor detection with narrow beam laser scanning (report 1). (1988)

Fundamental studies were performed in which halogen parallel lights and narrow beam He-Ne laser scanning were applied to the image diagnosis of breast lesions. The breast tissue was simulated by fresh milk as an opaque material. With halogen parallel lights, objects close to the light could not be detected, objects in the center were slightly detectable, and those close to the detector were visualized distinctly. Narrow beam scanning with He-Ne laser produced contrasting results: the closer the object was to the light, the better its detectability. However, as the diameter of the object decreased, detectability worsened. The results of the experiments indicated that small lesions in the opaque breast tissue may be detected by He-Ne laser with narrow beam scanning.
Drunk Drivers and Medical and Social Injury (1987)

Alcohol-related traffic injuries are a major cause of death, pain, and suffering and a major contributor to health care costs in the United States. We reviewed the medical and legal consequences of 252 motor vehicle accidents involving drivers admitted to St. Mary's Hospital between 1981 and 1985, with particular attention to patients with a blood alcohol concentration equal to or above the legally defined threshold for intoxication (100 mg per deciliter). There were 84 such patients, with a median blood alcohol level of 218.5 mg per deciliter. Few of these patients were referred either to alcoholism-rehabilitation programs or to the courts for prosecution. We conclude that both drunk drivers and the population at large are poorly served by current medical and legal practices. Because denial of reality and prevarication are hallmarks of alcoholism, we make two recommendations. First, in order to encourage physicians to refer all injured patients with high blood alcohol concentrations to detoxification and rehabilitation programs, injury to intoxicated drivers should be made a reportable condition. Second, prosecution for driving under the influence of alcohol should be made easier by simplifying the procedures for providing the courts with blood alcohol measurements obtained as part of normal clinical care. Physicians must act in the interest of their patients. The two recommended changes in current practice would help provide a firm framework within which physicians could advise patients about appropriate treatment for alcoholism. If such steps are not taken or are ineffective, vigorous legal action should be encouraged, because society has the right to demand that innocent people not be endangered by intoxicated people who drive motor vehicles.
Widely separate wavelength switching of single quantum well laser diode by injection-current control (1986)

It is demonstrated for the first time that by injection-current control, the lasing wavelength was able to be switched from the lowest (n=1) quantized state transition to the second (n=2) transition for a single quantum well laser diode. The separation in energy was as wide as &amp;gt;50 meV. This novel function of a laser was realized as a result of appropriately increased threshold gain. This diode, moreover, acted as a multiple wavelength-emitting laser.
Design considerations for high efficiency liquid crystal decentered microlens arrays for steering light (2010)

We have investigated the causes of low efficiency for optical beam steering devices based on liquid crystal decentered microlens arrays (DLAs). We show that the efficiency is effected by the relative phase of light exiting the individual lenses, the imperfect focusing of small lenses due to diffraction, the aberrations related to off-axis light going through a lens, and the diffraction spreading of light beams going through the DLA structure. A high steering efficiency of over 94.4% is demonstrated by modeling the transmitted light through the DLA with scalar diffraction theory. We also propose modified phase profiles for the lenses that are a function of angle that substantially improve the performance of these types of device over the unmodified profiles.
Bacterial vaginosis: emphasis on upper genital tract complications. (1989)

The term bacterial vaginosis is used to reflect the complex alterations of vaginal microorganisms and connotes the presence of a malodorous discharge without apparent inflammation. The normal vaginal flora is reviewed in order to better understand this syndrome. This article also discusses the frequency, clinical symptoms, diagnosis, and treatment of this condition.
Structure, Organization, and Chromosomal Location of the Gene Encoding a Form of Rice Soluble Starch Synthase (1995)

A rice (Oryza sativa L.) genomic clone encoding the gene for a form of soluble starch synthase (SSS1) and its 5'- and 3'-flanking regions has been isolated and sequenced. The SSS1 gene contained 15 exons interrupted by 14 introns. The exon/intron organization of the SSS1 gene was divergent from that of the rice Waxy gene coding for granule-bound starch synthase, thus suggesting that the SSS1 and granule-bound starch synthase genes have evolved from an ancestral gene in a different way or that the two genes are products of different ancestral genes that have converged during evolution. However, these two genes were closely located to each other on rice chromosome 6 at an approximate map distance of 5 centimorgans. The nucleotide sequence of the 5'-end region of the gene is unique because of the presence of some repetitive sequences.
Preliminary Observations on APOE ϵ4 Allele and Progression of Disability in Multiple Sclerosis (1999)

These preliminary observations suggest that APOE genotype may influence disease progression in MS. The APOE epsilon4 allele was not associated with an increased risk of MS or relapses.
[The effect of bakumondo-to on salivary secretion in Sjögren syndrome]. (1990)

The effect of a traditional chinese medicine 'Bakumondô tô' was evaluated on salivary secretion in thirty-eight patients with Sjögren's syndrome (SjS) and the results were compared with a matchen control group of patients treated with Hochûekki-tô. Hochûekki-tô is also one of the traditional chinese medicine. Tsumura Bakumondô-tô and Tsumura Hochûekki-tô (extract granules) were used. Daily dose was 9g and 7.5g respectively. Before looking into the effects of Bakumondô-tô on salivary secretion, we must define the reliability of the gum test. To avoid of learning effect, three sequential gum tests were needed. At the second gum test and the third gum test, no increase of salivary secretion was observed. So, we performed at least three gum test in each the patients studied. We have reached the following conclusion. First, in the Bakumondô-tô group the salivary secretion was significantly increased from 8.2 +/- 1.1ml (m +/- SE) to 11.4 +/- 1.4ml. (p less than 0.005) Second, in the Bakumondô-tô group, the increase in salivary secretion was 3.16 +/- 0.78ml which was significantly more than the increase in control group. (p less than 0.005) Third, in the course of long-term observation, the salivary secretion in patients under Bakumondô-tô treatment gradually increased. (r = 0.7290) Fourth, the improvement of salivary secretion under Bakumondô-tô treatment was marked in stage I and stage II of sialographical abnormalities of the salivary gland. Finally, Bakumondô-tô was very useful for managing oral manifestations in patients with SjS.
Enhanced expression of SPARC/osteonectin in the tumor-associated stroma of non-small cell lung cancer is correlated with markers of hypoxia/acidity and with poor prognosis of patients. (2003)

Secreted Protein Acidic and Rich in Cystein (SPARC)/osteonectin is a nonstructural matricellular protein involved in cell-matrix interaction during tissue remodeling and embryonic development. Using a novel monoclonal antibody (10-255), we examined immunohistochemically the patterns of SPARC expression in non-small cell lung cancer (NSCLC). High levels of SPARC in normal lung were confined exclusively to the bronchial cartilage. In NSCLC tissues, cancer cells were unreactive in 107 of 113 cases analyzed (95%), whereas substantial production of SPARC by stromal fibroblasts was noted in 42 of 113 cases (37%). Stromal SPARC was linked with tumor necrosis (P = 0.01) and, marginally, with node metastasis (P = 0.07), as well as with high levels of carbonic anhydrase 9 and LDH in cancer cells (P = 0.0001 and P = 0.01, respectively). SPARC was also coincident with enhanced levels of cancer cell differentiated embryo-chondrocyte expressed gene 1, hypoxia inducible factor 2alpha, and thymidine phosphorylase (P = 0.01, P = 0.05, and P = 0.03, respectively). Although endothelial reactivity for SPARC was noted only in small, immature vessels, SPARC production by stroma cells supported a high degree of vascular maturation (indicated by the presence of subendothelial lamina lucida). Survival analysis revealed a significant association of stromal SPARC with poor prognosis (P = 0.006), a finding that was also confirmed in multivariate models. In NSCLC, SPARC is selectively synthesized by the cells of the tumoral stroma. The strong association of this feature with markers of intratumoral hypoxia and acidity indicates an interesting link between cancer cell metabolism and the induction of a supportive stroma that favors cancer cell invasion and migration that lead to an ominous clinical outcome.
Product Application Focus: Stable Luciferase Reporter Cell Lines for Signal Transduction Pathway Readout Using GAL4 Fusion Transactivators (2001)

While GAL4 fusion activators have been widely used for dissecting signal transduction pathways in transient assays, there has been surprisingly little reported on utilizing cell lines with stably integrated fusion activators. To avoid problems with the efficiency and reproducibility inherent to transient transfection, we describe here the generation and characterization of HeLa reporter cell lines, which contain a stably integrated luciferase gene responsive to stably integrated and constitutively expressed GAL4-CREB or GAL4-Elk1 fusion activators. These cell lines exhibited extremely low basal luciferase expression but robust response to various extracellular stimuli or the expression of signaling molecules that resulted in elevated MAP kinase or PKA activities. This integrated two-component reporter system allows one to focus specifically on particular signaling pathway endpoints and the altered transactivation activity of either Elk1 or CREB. With the procedures described here, many novel cell-based assays can be developed by generating new reporter cell lines with medically important but difficult-to-transfect cell types, and by using different reporter genes or different fusion transactivator genes.
Oligonucleotide Therapeutics — A New Class of Cholesterol-Lowering Drugs (2017)

Another drug class may soon be added to cholesterol-lowering strategies: a chemically modified, small interfering RNA conjugated to the trivalent N-acetylgalactosamine. The siRNAs are oligonucleotide therapeutics, which destroy RNA before a protein is synthesized.
Kinetic Mechanism of Human DNA Ligase I Reveals Magnesium-dependent Changes in the Rate-limiting Step That Compromise Ligation Efficiency (2011)

DNA ligase I (LIG1) catalyzes the ligation of single-strand breaks to complete DNA replication and repair. The energy of ATP is used to form a new phosphodiester bond in DNA via a reaction mechanism that involves three distinct chemical steps: enzyme adenylylation, adenylyl transfer to DNA, and nick sealing. We used steady state and pre-steady state kinetics to characterize the minimal mechanism for DNA ligation catalyzed by human LIG1. The ATP dependence of the reaction indicates that LIG1 requires multiple Mg(2+) ions for catalysis and that an essential Mg(2+) ion binds more tightly to ATP than to the enzyme. Further dissection of the magnesium ion dependence of individual reaction steps revealed that the affinity for Mg(2+) changes along the reaction coordinate. At saturating concentrations of ATP and Mg(2+) ions, the three chemical steps occur at similar rates, and the efficiency of ligation is high. However, under conditions of limiting Mg(2+), the nick-sealing step becomes rate-limiting, and the adenylylated DNA intermediate is prematurely released into solution. Subsequent adenylylation of enzyme prevents rebinding to the adenylylated DNA intermediate comprising an Achilles' heel of LIG1. These ligase-generated 5'-adenylylated nicks constitute persistent breaks that are a threat to genomic stability if they are not repaired. The kinetic and thermodynamic framework that we have determined for LIG1 provides a starting point for understanding the mechanism and specificity of mammalian DNA ligases.
Two receptors for vasoactive intestinal polypeptide with similar specificity and complementary distributions. (1994)

Vasoactive intestinal polypeptide (VIP) has a variety of physiological effects. Pharmacological evidence suggesting that VIP acts via multiple receptors has been confirmed by the cloning of two VIP receptors (VIP1 and VIP2) with very different amino acid sequences. At both the VIP1 and the VIP2 receptor VIP, PHI, PACAP38, and PACAP27 have similar potency to each other. Only the VIP1 receptor is activated by secretin. The messenger RNAs (mRNAs) for the two receptors have completely different distributions as mapped by in situ hybridization histochemistry. VIP1 receptor mRNA is predominantly found in the lung, small intestine, thymus, and within the brain in the cerebral cortex and hippocampus. VIP2 receptor mRNA is present in a number of areas where VIP acts but VIP1 receptor mRNA is not present, including the stomach and testes. In the CNS VIP2 receptor mRNA is exclusively present in areas associated with neuroendocrine function, including several hypothalamic nuclei. In the periphery, it is also present in the pituitary and in pancreatic islets.