gebhart/patrepeval huggingface dataset:
COMBINATION PHARMACOTHERAPY: A MIXTURE OF SMALL DOSES OF NALTREXONE, FLUOXETINE, AND A THYROTROPIN-RELEASING HORMONE ANALOGUE REDUCES ALCOHOL INTAKE IN THREE STRAINS OF ALCOHOL-PREFERRING RATS (2000)

It is common to treat some diseases with more than one medication simultaneously. Since more than one neurotransmitter system is involved in alcohol-seeking behaviour, then a therapeutic approach that targets more than one system should be more effective in reducing alcohol intake than one addressing a single system. To test this hypothesis, we compared the efficacy of low doses of individual drugs reported to reduce voluntary alcohol drinking to the efficacy of a mixture of these agents at the same low doses in reducing alcohol intake in three strains of alcohol-preferring rats (P, HAD, and Fawn-Hooded). After establishment of a stable baseline for alcohol intake in a continuous access paradigm, each rat received separate single i.p. injections of relatively low doses of either naltrexone (2.0 mg/kg), fluoxetine (1.0 mg/kg), the thyrotropin-releasing hormone analogue TA-0910 (0.2 mg/kg), a mixture of all three drugs, or the vehicle at 09:30. Each rat received all treatments, with an inter-injection washout period of at least 3 days. Alcohol and water intakes were measured at 6 and 24 h, and food intake was measured at 24 h, after the injection. Our results show that individual drugs did not significantly affect food, water, or alcohol intake. However, the mixture significantly reduced alcohol intake in all three strains, but had no effect on food intake. Similar results were obtained when the HAD rats received an oral dose of the individual drugs or the mixture. When P rats were given an i.p. injection of the mixture for 10 consecutive days, there was a continued suppressing effect. These findings show that a combination treatment designed to target simultaneously serotonergic, dopaminergic, and opioidergic systems can reduce alcohol intake, even though the doses of the individual drugs in the mixture are relatively low and ineffective when given singly.
Oxidative Stress-Dependent Impairment of Cardiac-Specific Transcription Factors in Experimental Diabetes (2006)

Oxidative stress plays a key role in the pathogenesis of diabetic cardiomyopathy, which is characterized by myocyte loss and fibrosis, finally resulting in heart failure. The study looked at the downstream signaling whereby oxidative stress leads to reduced myocardial contractility in the left ventricle of diabetic rats and the effects of dehydroepiandrosterone (DHEA), which production is suppressed in the failing heart and prevents the oxidative damage induced by hyperglycemia in several experimental models. DHEA was given orally at a dose of 4 mg/rat per day for 21 d to rats with streptozotocin (STZ)-induced diabetes and genetic diabetic-fatty (ZDF) rats. Oxidative balance, advanced glycated end products (AGEs) and AGE receptors, cardiac myogenic factors, and myosin heavy-chain gene expression were determined in the left ventricle of treated and untreated STZ-diabetic rats and ZDF rats. Oxidative stress induced by chronic hyperglycemia increased AGE and AGE receptors and led to activation of the pleoitropic transcription factor nuclear factor-kappaB. Nuclear factor-kappaB activation triggered a cascade of signaling, which finally led to the switch in the cardiac myosin heavy-chain (MHC) gene expression from the alpha-MHC isoform to the beta-MHC isoform. DHEA treatment, by preventing the activation of the oxidative pathways induced by hyperglycemia, counteracted the enhanced AGE receptor activation in the heart of STZ-diabetic rats and ZDF rats and normalized downstream signaling, thus avoiding impairment of the cardiac myogenic factors, heart autonomic nervous system and neural crest derivatives (HAND) and myogenic enhancer factor-2, and the switch in MHC gene expression, which are the early events in diabetic cardiomyopathy.
Expression of vascular permeability factor/vascular endothelial growth factor in normal rat tissues (1993)

Vascular permeability factor (VPF)/vascular endothelial growth factor (VEGF) is a approximately 43-kDa secreted protein that has been shown in bioassays to induce endothelial proliferation, angiogenesis, and capillary hyperpermeability. VPF has been suggested to play an important role in the physiology of normal vasculature. To further elucidate the natural functions of VPF in vivo, the expression of VPF in normal tissues was examined using Northern blot analysis and in situ hybridization histochemistry. VPF mRNA is expressed in the brain, kidney, liver, lung, and spleen of the healthy adult rat. On Northern blots, the relative abundance of VPF mRNA observed in these tissues was highest in the lung and lowest in the spleen. As determined by in situ hybridization, the patterns of VPF expression are organ specific. Hybridization of an antisense VPF probe was concentrated in the cerebellar granule cell layer of the brain and in the glomeruli and tubules of the kidney. In the liver and lung, intense hybridization was observed homogeneously throughout both tissues, demonstrating that VPF mRNA is present in virtually every hepatocyte and pulmonary alveolar cell. Hybridization to the spleen was weaker and more diffuse. The widespread expression and organ-specific distribution of VPF mRNA in normal rat tissues supports the suggestion of an extensive role for this factor in the physiology of normal vasculature.
In vitro Paracoccidioides brasiliensisbiofilm and gene expression of adhesins and hydrolytic enzymes (2015)

Paracoccidioides species are dimorphic fungi that initially infect the lungs but can also spread throughout the body. The spreading infection is most likely due to the formation of a biofilm that makes it difficult for the host to eliminate the infection. Biofilm formation is crucial for the development of infections and confines the pathogen to an extracellular matrix. Its presence is associated with antimicrobial resistance and avoidance of host defenses. This current study provides the first description of biofilm formation by Paracoccidioides brasiliensis (Pb18) and an analysis of gene expression, using real-time PCR, associated with 3 adhesins and 2 hydrolytic enzymes that could be associated with the virulence profile. Biofilm formation was analyzed using fluorescence microscopy, scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM). Metabolic activity was determined using the XTT reduction assay. P. brasiliensis was able to form mature biofilm in 144 h with a thickness of 100 μm. The presence of a biofilm was found to be associated with an increase in the expression of adhesins and enzymes. GP43, enolase, GAPDH and aspartyl proteinase genes were over-expressed, whereas phospholipase was down-regulated in biofilm. The characterization of biofilm formed by P. brasiliensis may contribute to a better understanding of the pathogenesis of paracoccidioidomycosis as well as the search for new therapeutic alternatives; while improving the effectiveness of treatment.
A 277-GHz f/sub max/ transferred-substrate heterojunction bipolar transistor (1997)

We report a AlInAs-GaInAs transferred-substrate heterojunction bipolar transistor (HBT). The transferred-substrate process permits fabrication of narrow and aligned collector-base and emitter-base junctions, reducing the collector-base capacitance and increasing the device f <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">max</sub> . A device with aligned 0.7-μm emitter and 1.6-μm collector stripes has extrapolated 277 GHz f <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">max</sub> and 127 GHz f/sub /spl tau//, respectively.
Inflammaging as a prodrome to Alzheimer's disease (2008)

Recently, the term "inflammaging" was coined by Franceshci and colleagues to characterize a widely accepted paradigm that ageing is accompanied by a low-grade chronic up-regulation of certain pro-inflammatory responses. Inflammaging differs significantly from the traditional five cardinal features of acute inflammation in that it is characterized by a relative decline in adaptive immunity and T-helper 2 responses and is associated with increased innate immunity by cells of the mononuclear phagocyte lineage. While the over-active innate immunity characteristic of inflammaging may remain subclinical in many elderly individuals, a portion of individuals (postulated to have a "high responder inflammatory genotype") may shift from a state of "normal" or "subclinical" inflammaging to one or more of a number of age-associated diseases. We and others have found that IFN-gamma and other pro-inflammatory cytokines interact with processing and production of Abeta peptide, the pathological hallmark feature of Alzheimer's disease (AD), suggesting that inflammaging may be a "prodrome" to AD. Although conditions of enhanced innate immune response with overproduction of pro-inflammatory proteins are associated with both healthy aging and AD, it is suggested that those who age "well" demonstrate anti-inflammaging mechanisms and biomarkers that likely counteract the adverse immune response of inflammaging. Thus, opposing the features of inflammaging may prevent or treat the symptoms of AD. In this review, we fully characterize the aging immune system. In addition, we explain how three novel treatments, (1) human umbilical cord blood cells (HUCBC), (2) flavanoids, and (3) Abeta vaccination oppose the forces of inflammaging and AD-like pathology in various mouse models.
Psychopathology in Adopted-Away Offspring of Biologic Parents With Antisocial Behavior (1978)

• A study of 246 adoptees aged 10 to 37 years separated at birth from biologic parents is used to study genetic heritability of antisocial behavior and to delineate the extent and quality of "antisocial spectrum" conditions. Evidence is presented for a genetic factor in adoptee antisocial behavior and for the following as "spectrum" conditions: (1) hysteria in adult females (Briquet's syndrome) or multiple somatic complaints without medical explanation in younger female subjects and (2) mood swings possibly associated with the symptom of audible thoughts.
Interleukin-2-induced, melanoma-specific T cells recognize camel, an unexpected translation product ofLAGE-1 (1999)

Melanoma-specific cytotoxic T lymphocytes (CTLs) were induced by in vitro stimulation of peripheral blood mononuclear cells of a melanoma patient with autologous IL-2-producing melanoma 518/IL2.14 cells. CTL clone 1/29 recognized, in addition to autologous melanoma cell lines, a panel of HLA-A*0201-expressing allogeneic melanoma cell lines but was not reactive with normal melanocytes. Here, we report the full molecular characterization of the target structure for CTL 1/29, which was identified by cDNA expression cloning. The recognized antigen was named CAMEL (CTL-recognized antigen on melanoma). The CAMEL cDNA turned out to be derived from the LAGE-1 gene, a recently described tumor antigen that is strongly homologous to NY-ESO-1. CAMEL, however, is not encoded by the putative open reading frame (ORF) of LAGE-1 but by an alternative frame starting from the second ATG of the mRNA. The first 11 amino acids of the CAMEL protein, MLMAQEALAFL, constitute the epitope of CTL 1/29. This epitope is also encoded by a similar alternative ORF in NY-ESO-1. In summary, CTL induction with IL-2-transfected melanoma cells has revealed a new tumor antigen that may serve as a target for immunotherapy.
Induction of histone acetylation and growth regulation in eryrthroleukemia cells by 4-phenylbutyrate and structural analogs. (1999)

The objective of this investigation was to study the relationship between histone acetylation and growth inhibition by 4-phenylbutyrate and structural analogs. Inhibition of growth of DS19 mouse erythroleukemia cells and K562 human leukemic cells by 4-phenylbutyrate did not appear to be mediated by glutamine depletion. Vanadate blocked differentiation of DS19 cells but did not affect the hyperacetylation of histones. 2-phenylbutyrate was a more effective inhibitor of cell proliferation than 3-phenylbutyrate but was less effective as an inducer of histone acetylation. 4-Phenylbutyrate was a more effective inhibitor of histone deacetylase and inducer of histone acetylation than the structural analogs examined including 2- and 3-phenylbutyrate, cinnamate, methoxycinnamate, 2-phenoxybutyrate and phenoxyacetate.
The mechanism of action of MPTP-induced neuroinflammation and its modulation by melatonin in rat astrocytoma cells, C6 (2010)

The 1-methyl-4-phenyl 1,2,3,6 tetrahydropyridine (MPTP) induces reactive astrogliosis, the cellular manifestation of neuroinflammation, in various models of Parkinson's disease (PD), but its mechanism of action on astrocytes is not understood. The effect of melatonin on MPTP-induced neuroinflammation in astrocytes is also not known. The present study demonstrated that MPTP treatment of rat astrocytoma cells, C6 for 24 h significantly increased nitrative and oxidative stress and intracellular calcium (Ca2++) level. MPTP also activated phosphorylated p38 mitogen activated protein kinase (P-p38 MAPK) and up-regulated expressions of inflammatory proteins. Moreover, MPTP modulated mRNA expressions of pro-inflammatory cytokine genes via activating nuclear factor kappa-B (NF-kB) translocation. Treatment of melatonin with MPTP reversed all these MPTP-induced changes. Study with deprenyl demonstrates that MPTP is inducing neuroinflammation in astrocytoma cells. The present findings elucidated the molecular mechanism of MPTP-induced neuroinflammation and its modulation by melatonin in astrocytoma cells (C6).
Side Reaction to Measles Vaccination Suggesting the Arthus Phenomenon (1967)

LOCAL damage due to antigen–antibody reaction has been known since the original work of Arthus1 , 2 in 1903. A reaction similar to the Arthus phenomenon3 has been observed in children given inactivated-measles-virus vaccine followed by live-virus vaccine. This method has been introduced to avoid the side reactions resulting from certain live-virus vaccines.4 , 5 Children of the age group from twelve months to five years were vaccinated in my practice against measles by a regimen of a single injection of commercial inactivated-virus vaccine. The vaccine was a filtered, alum-precipitated preparation of measles virus derived from the Edmonston strain, propagated in monkey-kidney tissue-culture cells . . .
Studies on the Mechanism of Stabilization of Partially Phosphorothioated Oligonucleotides Against Nucleolytic Degradation (1997)

The use of chimeric oligonucleotides (ODN), in which certain phosphodiester internucleoside linkages are replaced by phosphorothioate (PS) linkages to provide protection against degradation by nucleases, is gaining increasing attention because of their significantly decreased propensity for nonantisense effects as compared with uniformly PS-modified ODN. We have recently reported that partially PS-modified ODN, in which end- capping is used to prevent hydrolysis by exonucleases in combination with PS protection at internal pyrimidine residues which are the major sites of endonuclease degradation, are surprisingly stable in serum. The present study investigates an additional role of the backbone modification in the stabilization of ODN against nucleolytic degradation. We show that the stability of an unmodified ODN in fetal bovine serum is significantly enhanced in the presence of PS-modified ODN. The magnitude of stabilization is strongly dependent on the type and degree of backbone modification. The observed effect is stronger for PS-modified ODN than for methylphosphonate (MP)-modified ODN and increases as the number of PS linkages in the ODN increases. Thus, nuclease stability of partially PS-modified ODN is not only caused by direct prevention of nuclease attack at the phosphate center but is additionally supported by interference of the nucleases with the PS groups of ODN, resulting in decreased degradation. As the degree of many nonantisense effects caused by ODN, such as protein interactions and B cell stimulation, is dependent on the backbone modification, our results may have implications for the use of non-ODN nuclease inhibitors to reduce undesirable side effects.
Molecular analysis of a heteroclitic T cell response to the immunodominant epitope of sperm whale myoglobin. Implications for peptide partial agonists (1995)

We have investigated the molecular basis for binding and Ag presentation of an immunodominant Th cell determinant of sperm whale myoglobin, a prototype amphipathic helical structure in the native protein. A series of peptides with three different substitutions at each position were evaluated for binding to the class II MHC molecule I-Ad and for activation of two T cell clones with distinct fine specificity, to determine the role of each residue. The assignment of MHC binding and TCR binding residues is consistent with a peptide bound as a twisted beta-strand, with 130 degrees twist similar to that of the influenza hemagglutinin peptide crystallized in the groove of HLA-DR1. This twist gives the peptide amphipathicity, with a periodicity similar to an alpha-helix without its being a helix. Two substituted peptides were discovered to be heteroclitic, but by different molecular mechanisms, one involving gain of a favorable residue and one involving loss of an unfavorable one. Complexes of both peptides with I-Ad had enormously higher affinity for the TCR, but peptide affinity for the MHC molecule was not increased, such that the wild-type peptide acted as a partial agonist and inhibited the response to the heteroclitic ones. Moreover, the magnitude of response was elevated in a way that could not be mimicked by the wild-type peptide even at higher concentration. These results suggest a TCR dwell time requirement for optimal signal transduction that may help explain the mechanism of partial agonism.
Biomechanically Articulated Chair Concept and Prototypes (1997)

&lt;div class="htmlview paragraph"&gt;The human torso includes three major segments, the thoracic (rib cage) segment, lumbar segment, and pelvic segment to which the thighs are attached. The JOHN model was developed to represent the positions and movements of these torso segments along with the head, arms, and legs. Using the JOHN model, a new seat concept has been developed to support and move with the torso segments and thighs. This paper describes the background of the biomechanically articulated chair (BAC) and the development of BAC prototypes. These BAC prototypes have been designed to move with and support the thighs, pelvis, and rib cage through a wide variety of recline angles and spinal curvatures. These motions have been evaluated with computer modeling and with initial experience of human subjects. Results from computer modeling and human subjects show that the BAC will allow a broad range of torso postures. In a BAC, people can choose between two basic modes of operation:&lt;/div&gt; &lt;div class="htmlview paragraph"&gt; &lt;ol class="list nostyle"&gt; &lt;li class="list-item"&gt; &lt;span class="li-label"&gt;1.&lt;/span&gt; &lt;div class="htmlview paragraph"&gt;the articulations of the BAC can will follow and support their selections of torso posture, or&lt;/div&gt; &lt;/li&gt; &lt;li class="list-item"&gt; &lt;span class="li-label"&gt;2.&lt;/span&gt; &lt;div class="htmlview paragraph"&gt;the components of the BAC can be positioned and the user's posture will respond to the positions of the BAC.&lt;/div&gt; &lt;/li&gt; &lt;/ol&gt; &lt;/div&gt; &lt;div class="htmlview paragraph"&gt;The BAC prototypes demonstrate that seats can be designed which allow and support a broad range of seating postures and that seats can move with people as they change their posture.&lt;/div&gt;
Design of expression vectors for RNA interference based on miRNAs and RNA splicing (2006)

RNA interference (RNAi) mediates sequence‐specific post‐transcriptional gene silencing in many eukaryotes and is used for reverse genetic studies and therapeutics. RNAi is triggered by double‐stranded small interfering RNAs (siRNAs), which can be processed from small hairpin RNAs generated from an expression vector. In some recently described vectors, the siRNAs are expressed from synthetic stem‐loop precursors of microRNAs (miRNAs) driven by polymerase II promoters. We have designed new RNAi vectors, designated pSM155 and pSM30, that take into consideration miRNA processing and RNA splicing by placing the miRNA‐based artificial miRNA expression cassettes inside of synthetic introns. Like the original miRNA vectors, we show that the pSM155 and pSM30 constructs efficiently down‐regulate expression of firefly luciferase and an endogenous gene, phospholipase D2. Moreover, the expression of a coexpressed fluorescent marker is substantially improved by this new design. Another improvement of these new vectors is incorporation of two inverted Bsm BI sites placed internal to the arms of the new miRNA‐based vectors, so oligos used for cloning are shorter and the cost is reduced. These RNAi vectors thus provide new tools for gene suppression.
Gastric emptying and dyspeptic symptoms in patients with gastroesophageal reflux. (1996)

Gastric emptying of a solid meal is markedly delayed in patients with gastroesophageal reflux. However, no direct causal link was found between delayed emptying and reflux. Our data suggest the presence of a motility disorder in gastroesophageal reflux which is not confined to the esophagogastric junction.
Expression of the glucose oxidase gene from Aspergillus niger in Hansenula polymorpha and its use as a reporter gene to isolate regulatory mutations (1993)

The glucose oxidase gene (god) from Aspergillus niger was expressed in Hansenula polymorpha using the methanol oxidase promoter and transcription termination region and the MF-alpha leader sequence from Saccharomyces cerevisiae to direct secretion. The expression cassette was cloned into the S. cerevisiae vector YEp13 and used to transform H. polymorpha strain A16. In the initial transformants plasmid replication was unstable, but was stabilized by a growth regime consisting of alternating cycles of selective and non-selective growth. The stabilized strain was grown to high cell density by fed-batch fermentation. Upon induction of the MOX promoter, glucose oxidase synthesis was initiated. At the end of the fermentation, the culture density was 76 g dry weight/1 and 108 IU/ml (0.5 g/1 or 0.65% dry weight) glucose oxidase was found in the culture medium; a further 86 IU/ml (0.43 g/1 or 0.56% dry weight) was recovered from the cell lysate. A plate assay was used to monitor glucose oxidase levels in individual colonies. This was then used to isolate mutants which showed abnormal regulation of god expression or which showed an altered pattern of secretion. One mutant, which showed increased production of glucose oxidase, was grown to high cell density by fed-batch fermentation (100.6 g/l) and produced 445 IU/ml(2.25 g/l or 2.2% dry weight) extracellularly and 76 IU/ml (0.38 g/l or 0.4% dry weight) intracellularly. The mutant thus not only increased total production but exported 83% of the total enzyme made compared to 55% in the parent strain.