gebhart/patrepeval huggingface dataset:
The Expression of Adenoviral Mediated gfp Reporter Gene in Tumor Cells Induced and Regulated by Irradiation. (2001)

In order to establish a radiation inducible gene expression system for cancer gene therapy, the promoter sequence of radiation-inducible Egr-1 gene was amplified from genomic DNA of BALB/c mouse with PCR method, and linked to gfp reporter gene. Then the pEgr-gfp expression cassette was subcloned into an adenoviral shuttle plasmid to generate recombinant adenovirus of AdEgr-GFP by using a novel, high efficient method of homologous recombination in bacteria. After infection with AdEgr-GFP, MM45T.Li tumor cells were exposed to different doses of gamma-irradiation from 0 Gy to 15 Gy in vitro. The percentage of GFP expression positive cells increased greatly in a dose-dependent manner as detected by FACS and Western blot analysis. For in vivo study, AdEgr-GFP were injected intratumorally, and tumor site received different doses of local gamma-irradiation 48 h after injection, and after 8 h the tumor samples were biopsed for investigating the GFP expression. Tumor tissue image analysis revealed that gamma-irradiation could markedly increase GFP expression in a dose-dependent manner as compared with that of non-irradiated control group. Our results indicate that the irradiation can effectively control adenoviral-mediated GFP expression in tumor cells via Egr-1 promoter, and these data laid basis for further gene radiotherapy study.
Inhibition of rat glomerular visceral epithelial cell growth by heparin (1988)

The effect of several glycosaminoglycans and sulfated polysaccharides on the growth of cultured rat glomerular visceral epithelial cells (GEC) was studied in vitro. Heparin, one preparation of heparan sulfate proteoglycan, dextran sulfate, and pentosan polysulfate significantly inhibited the growth of several GEC clones studied (36.0-77.1% inhibition at 100 micrograms/ml). Other glycosaminoglycans studied did not affect GEC growth. Growth inhibition by heparin was dose related and did not appear to reflect cytotoxicity. Heparins with high or low affinity for antithrombin inhibited growth to similar degrees. When heparin was fractionated into high- and low-anticoagulant activity fractions by physicochemical means the high activity fraction displayed significantly greater growth inhibition. The degree of growth inhibition significantly correlated with serum concentration in the media (r = 0.64; P less than 0.001). Removal of heparin binding factors from serum resulted in a loss of this correlation as well as less overall growth inhibition. These experiments suggest that interactions of GEC with heparan sulfates and other heparin-like molecules in the extracellular matrix may be important in the control of GEC growth.
Reactions of ozone with human skin lipids: Sources of carbonyls, dicarbonyls, and hydroxycarbonyls in indoor air (2009)

This study has used proton transfer reaction-mass spectrometry (PTR-MS) for direct air analyses of volatile products resulting from the reactions of ozone with human skin lipids. An initial series of small-scale in vitro and in vivo experiments were followed by experiments conducted with human subjects in a simulated office. The latter were conducted using realistic ozone mixing ratios (approximately 15 ppb with occupants present). Detected products included mono- and bifunctional compounds that contain carbonyl, carboxyl, or alpha-hydroxy ketone groups. Among these, three previously unreported dicarbonyls have been identified, and two previously unreported alpha-hydroxy ketones have been tentatively identified. The compounds detected in this study (excepting acetone) have been overlooked in surveys of indoor pollutants, reflecting the limitations of the analytical methods routinely used to monitor indoor air. The results are fully consistent with the Criegee mechanism for ozone reacting with squalene, the single most abundant unsaturated constituent of skin lipids, and several unsaturated fatty acid moieties in their free or esterified forms. Quantitative product analysis confirms that squalene is the major scavenger of ozone at the interface between room air and the human envelope. Reactions between ozone and human skin lipids reduce the mixing ratio of ozone in indoor air, but concomitantly increase the mixing ratios of volatile products and, presumably, skin surface concentrations of less volatile products. Some of the volatile products, especially the dicarbonyls, may be respiratory irritants. Some of the less volatile products may be skin irritants.
Effect of Two Intensive Statin Regimens on Progression of Coronary Disease (2011)

Maximal doses of rosuvastatin and atorvastatin resulted in significant regression of coronary atherosclerosis. Despite the lower level of LDL cholesterol and the higher level of HDL cholesterol achieved with rosuvastatin, a similar degree of regression of PAV was observed in the two treatment groups. (Funded by AstraZeneca Pharmaceuticals; ClinicalTrials.gov number, NCT000620542.).
Glucocorticoids induce insulin resistance independent of GR in the liver (2012)

Glucocorticoids (GC) are potent anti-inflammatory drugs which are widely used in steroid therapy for autoimmune diseases. But besides their beneficial effects, long term treatment induces insulin resistance leading to type 2 diabetes. Until now, the precise molecular mechanisms how GCs induce insulin resistance are ill-defined. GCs act via the glucocorticoid receptor (GR) that can alter gene expression via two different modes of action: either by protein-protein interaction of the monomeric GR with transcription factors such as AP-1 and NF-κB or by direct binding as a homodimer to glucocorticoid response elements (GREs) in the promoter region of target genes. Traditionally GRE induced expression of gluconeogenetic enzymes in the liver by the GR was assumed to be responsible for insulin resistance due to excessive gluconeogenesis.
Expansion and contraction of rhesus macaque DRB regions by duplication and deletion. (1994)

Previous sequence analysis of the rhesus macaque MHC (MhcMamu) class II DRB region has allowed the detection of at least 34 alleles belonging to different lineages. In this communication, 36 new Mamu-DRB alleles are reported. The gene content of the DRB region has been determined for several homozygous animals of consanguineous origin. As in other primates, the number of DRB genes present per haplotype is not constant, varying from two to six genes in rhesus macaques. Six major groups of DRB haplotypes have been defined in our rhesus macaque colony. Two haplotype groups were found to carry, as well as other Mamu-DRB genes, two genes that cluster into distinct HLA-DRB1 lineages. In one of these two groups, a haplotype harbors another two sets of DRB alleles that belong to the Mhc-DRB6 and -DRB*W6 lineages, respectively. Such a haplotype was probably generated by duplication, and our data suggest that after this particular expansion of the DR region, one of the duplicated Mamu-DRB6 alleles was the target of an Alu insertion. Although certain transspecies allelic lineages are evolutionarily stable, and have been conserved for at least 36 million years, the rhesus macaque class II haplotypes differ significantly from those found in humans, chimpanzees, and gorillas. Mhc-DRB regions are therefore comparatively unstable over longer evolutionary time spans, with regard to both the number of genes and the gene content, and must have been subjected to expansion and contraction.
Glucuronides in the gut: Sugar-driven symbioses between microbe and host (2017)

The intestinal milieu is astonishingly complex and home to a constantly changing mixture of small and large molecules, along with an abundance of bacteria, viral particles, and eukaryotic cells. Such complexity makes it difficult to develop testable molecular hypotheses regarding host-microbe interactions. Fortunately, mammals and their associated gastrointestinal (GI) microbes contain complementary systems that are ideally suited for mechanistic studies. Mammalian systems inactivate endobiotic and xenobiotic compounds by linking them to a glucuronic acid sugar for GI excretion. In the GI tract, the microbiota express β-glucuronidase enzymes that remove the glucuronic acid as a carbon source, effectively reversing the actions of mammalian inactivation. Thus, by probing the actions of microbial β-glucuronidases, and by understanding which substrate glucuronides they process, molecular insights into mammalian-microbial symbioses may be revealed amid the complexity of the intestinal tract. Here, we focus on glucuronides in the gut and the microbial proteins that process them.
Effect on transformation of mutations in the early region 1b-encoded 21- and 55-kilodalton proteins of adenovirus 5 (1984)

It is well established that the adenovirus 5 genes responsible for the initiation and maintenance of the transformed cell reside in the early region 1a and 1b genes, but it remains unclear how the polypeptides encoded in these genes mediate their functions. To probe the function of the early region 1b-encoded 55- and 21-kilodalton (kd) polypeptides during this process, a series of viral mutants was engineered so that they contained deletions or insertions at 5.4, 5.7, 7.9, or 9.6 map units. By means of either an overlap recombination procedure involving H5dl314 (delta 3.7 to 4.6 map units) cleaved with ClaI, or a marker rescue procedure involving H5dl312 (delta 1.2 to 3.8 map units), viral mutants were isolated by their ability to produce plaques on KB cell line 18 cells, which constitutively express only viral early region 1b functions. DNA sequence analysis confirmed that the series of mutants generated differed in their abilities to express the 21- or the 55-kd polypeptides, or both. Upon infection of cloned rat embryo fibroblast cells with viruses containing mutations affecting the 55-kd protein, the transformation frequency decreased as the size of the predicted truncated polypeptide decreased. Although all of the foci generated by the 55-kd protein mutants were indistinguishable from the foci induced by wild-type virus, they displayed an inefficient ability to grow in soft agar, again in relation to the size of the truncated polypeptide. In contrast, if cloned rat embryo fibroblast cells were transfected with viral DNA, the defectiveness in transformation observed after infection with virions was not as dramatic. However, all of the viruses containing 21-kd mutations were transformation defective, regardless of the mode by which the viral nucleic acid was introduced into the cell.
CHEMICAL SYNTHESIS OF PEPTIDES AND PROTEINS (1988)

The Hippo pathway was initially discovered in Drosophila melanogaster as a key regulator of tissue growth. It is an evolutionarily conserved signaling cascade regulating numerous biological processes, including cell growth and fate decision, organ size ...Read More
Infusion of α-galactosidase A reduces tissue globotriaosylceramide storage in patients with Fabry disease (2000)

Fabry disease is a lysosomal storage disorder caused by a deficiency of the lysosomal enzyme alpha-galactosidase A (alpha-gal A). This enzymatic defect results in the accumulation of the glycosphingolipid globotriaosylceramide (Gb(3); also referred to as ceramidetrihexoside) throughout the body. To investigate the effects of purified alpha-gal A, 10 patients with Fabry disease received a single i.v. infusion of one of five escalating dose levels of the enzyme. The objectives of this study were: (i) to evaluate the safety of administered alpha-gal A, (ii) to assess the pharmacokinetics of i.v.-administered alpha-gal A in plasma and liver, and (iii) to determine the effect of this replacement enzyme on hepatic, urine sediment and plasma concentrations of Gb(3). alpha-Gal A infusions were well tolerated in all patients. Immunohistochemical staining of liver tissue approximately 2 days after enzyme infusion identified alpha-gal A in several cell types, including sinusoidal endothelial cells, Kupffer cells, and hepatocytes, suggesting diffuse uptake via the mannose 6-phosphate receptor. The tissue half-life in the liver was greater than 24 hr. After the single dose of alpha-gal A, nine of the 10 patients had significantly reduced Gb(3) levels both in the liver and shed renal tubular epithelial cells in the urine sediment. These data demonstrate that single infusions of alpha-gal A prepared from transfected human fibroblasts are both safe and biochemically active in patients with Fabry disease. The degree of substrate reduction seen in the study is potentially clinically significant in view of the fact that Gb(3) burden in Fabry patients increases gradually over decades. Taken together, these results suggest that enzyme replacement is likely to be an effective therapy for patients with this metabolic disorder.
Immune dysfunction in patients with diabetes mellitus (DM) (1999)

Patients with diabetes mellitus (DM) have infections more often than those without DM. The course of the infections is also more complicated in this patient group. One of the possible causes of this increased prevalence of infections is defects in immunity. Besides some decreased cellular responses in vitro, no disturbances in adaptive immunity in diabetic patients have been described. Different disturbances (low complement factor 4, decreased cytokine response after stimulation) in humoral innate immunity have been described in diabetic patients. However, the clinical relevance of these findings is not clear. Concerning cellular innate immunity most studies show decreased functions (chemotaxis, phagocytosis, killing) of diabetic polymorphonuclear cells and diabetic monocytes/macrophages compared to cells of controls. In general, a better regulation of the DM leads to an improvement of these cellular functions. Furthermore, some microorganisms become more virulent in a high glucose environment. Another mechanism which can lead to the increased prevalence of infections in diabetic patients is an increased adherence of microorganisms to diabetic compared to nondiabetic cells. This has been described for Candida albicans. Possibly the carbohydrate composition of the receptor plays a role in this phenomenon.
Molecular mechanisms of mesenchymal stem cell differentiation towards osteoblasts (2013)

Bone is a dynamic tissue that is constantly renewed by the coordinated action of two cell types, i.e., the bone-resorbing osteoclasts and the bone-forming osteoblasts. However, in some circumstances, bone regeneration exceeds bone self repair capacities. This is notably often the case after bone fractures, osteolytic bone tumor surgery, or osteonecrosis. In this regard, bone tissue engineering with autologous or allogenic mesenchymal stem cells (MSCs) is been widely developed. MSCs can be isolated from bone marrow or other tissues such as adipose tissue or umbilical cord, and can be implanted in bone defects with or without prior amplification and stimulation. However, the outcome of most pre-clinical studies remains relatively disappointing. A better understanding of the successive steps and molecular mechanisms involved in MSC-osteoblastic differentiation appears to be crucial to optimize MSC-bone therapy. In this review, we first present the important growth factors that stimulate osteoblastogenesis. Then we review the main transcription factors that modulate osteoblast differentiation, and the microRNAs (miRs) that inhibit their expression. Finally, we also discuss articles dealing with the use of these factors and miRs in the development of new bone MSC therapy strategies. We particularly focus on the studies using human MSCs, since significant differences exist between osteoblast differentiation mechanisms in humans and mice for instance.
Uptake and Metabolism of Plasma Glutamine by the Small Intestine (1974)

Abstract An isolated, vascularly perfused preparation of rat intestine extracted large amounts of glutamine (75 µmoles per hour), but no other amino acid, from a recirculated blood perfusate. With l-[U-14C]glutamine, the carbon was partly incorporated into tissue acid-insoluble material (14%) and the rest reappeared with little delay in intestinal venous blood in CO2 (57%), citrulline (6%), proline (5%), and organic acids (18%), predominantly citric acid and lactic acid. Perfusate glutamine was the source of 32% of the CO2 produced by the preparation, although the perfusate contained 10 to 15 mm glucose. Most glutamine uptake and metabolism occurred in the small intestinal mucosal cells and, from analyses of labeled tissue metabolites, appeared to proceed via glutamic acid. The rapid flow of glutamine carbon through mucosa may be explained in part by the small glutamine pool, only 0.2 µmole per g of tissue. Glutamine nitrogen taken up by intestine could be approximately accounted for by the quantities of citrulline (34%), alanine (33%), ammonia (23%), and proline (10%) released back into the perfusate. Glutamine uptake comparable to that found in the isolated organ was observed in vivo, from arteriovenous concentration measurements across intestine in fasted dogs, cats, hamsters, monkeys, and conventional and germ-free rats. Twenty-five to 33% of plasma glutamine was extracted in each pass through the tissue. Glutamine uptake persisted in rats during transport of large amounts of glutamic acid from the intestinal lumen into the blood and in rats injected with 6-diazo-5-oxo-l-norleucine. The results of these studies suggest that glutamine derived from blood is an important respiratory substrate for cells in the small intestinal mucosa and that intestine is a major site for metabolism of glutamine released into the circulation by other tissues.
Erfaringer med rådmåling i træer (2009)

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Postnatal Development of the Cruciate Ligament Insertions in the Rat Knee (1997)

The postnatal structural remodelling and calcification patterns in the insertions (entheses) of both cruciate ligaments were studied in a rat model with histology and immunohistochemical analysis of collagens types I and II. In the neonate, both ligaments which labelled only for type I collagen attached to epiphyseal cartilage which solely labelled for collagen type II. The entheses calcified between days 20 and 35, and a subchondral bone plate formed under the entheses between days 30 and 55. Thus, within a period of 35 days the tissue to which the ligaments attached increased multifold in stiffness. Interestingly, the process of enthesial calcification and formation of compact bone did not happen simultaneously in both ligaments, not even synchronous at both ends of the same ligament or within a single insertion. This asynchronous calcification of the different knee ligament insertions may make the sudden change in mechanical environment at the entheses less dramatic for the ligaments and knee joint surfaces as anticipated from mechanical models. In addition, a fibrocartilaginous tissue, rich in collagen type II, formed in the ligament at a time when the epiphyseal cartilage was replaced by bone, and grew wider with time. The interposition of a fibrocartilaginous zone in the insertion may diminish the sudden change in stiffness between ligament soft tissue and hard bone.
Cholesterol Production in Obesity (1971)

Sterol-balance studies were performed in 10 control subjects, 10 normolipidemic obese patients, and 10 hypertriglyceridemic (type IV, mostly obese) patients on a low-cholesterol solid-food diet. Fecal elimination of cholesterol was markedly elevated in the overweight patients and tended to be high in the hypertriglyceridemic subjects also. A significant correlation was found between body weight and fecal excretion of neutral, acidic, and total steroids, indicating that the greater the body weight the higher was the rate of cholesterol synthesis. Sterol-balance data in obese subjects showed that excess daily cholesterol production roughly amounted to 20 mg/kg of adipose tissue. The control subjects produced only 12 mg/kg of body weight daily. Thus, obesity is associated with an increased rate of cholesterol synthesis in man. However, the correlation between serum cholesterol concentration and cholesterol production was low, suggesting that the overall rate of cholesterol synthesis was not the only factor determining the serum cholesterol level. That enhanced cholesterol production is not an irreversible phenomenon in obese subjects was indicated by the normalization of sterol-balance values in three overweight patients after their weights had been reduced by total fast followed by a low-calorie diet.
Overexpression of bcl-2 protects prostate cancer cells from apoptosis in vitro and confers resistance to androgen depletion in vivo. (1995)

Normal (nonneoplastic) human prostatic secretory epithelial cells do not express the bcl-2 protein. However, a recent immunohistochemical survey of neoplastic human prostate tissues showed that a fraction of primary untreated prostate adenocarcinoma cells expressed this apoptosis-suppressing oncoprotein at significant levels (Colombel et al., Am. J. Pathol., 143: 390-400, 1993). Additionally, a number of hormone-refractory prostatic adenocarcinomas obtained from hormonally-treated patients (subsequent to surgical or drug castration therapy) were examined and were found to be uniform in their elevated expression of bcl-2 oncoprotein. The results of this preliminary survey imply that bcl-2 expression distinguishes a subgroup of primary human prostate cancers and that the expression of this protein might be a factor enabling prostate cancer cells to survive in an androgen-deprived environment. The current study was undertaken to determine the degree to which overexpression of bcl-2 can protect human prostate cancer cells from apoptotic stimuli in vitro and in vivo. Human prostate cancer cells (LNCaP) were transfected with a neomycin-selectable eucaryotic expression vector containing cDNA encoding human bcl-2. Transfected clonal variants that express bcl-2 protein (LNCaP/bcl-2) were unaltered with regard to their basal growth rate in 10% serum-containing medium, or with regard to their expression of the differentiated human prostate cell gene products prostate-specific antigen or androgen receptor protein. The bcl-2-transfected clones were altered, however, with regard to their growth rate in charcoal-stripped serum lacking dihydrotestosterone. Additionally, in contrast to the parental or control-transfected cell lines, LNCaP/bcl-2 cells were highly resistant to a variety of apoptotic stimuli in vitro including serum starvation and 10 nM phorbol ester (phorbol 12-myristate 13-acetate) supplementation of the medium. Lastly, the overexpression of bcl-2 by these prostate cancer cells altered their tumorigenic potential in a nude mouse assay. s.c. injections of 10(6) LNCaP/bcl-2 cells into male nude mice resulted in earlier and larger tumor formation compared to an equivalent injection of parental or control-transfected LNCaP cells. When these variant cell lines were injected into castrated male nude mice, only the LNCaP/bcl-2-transformed cells gave rise to tumors. Moreover, LNCaP/bcl-2 tumors grown in intact male nude mice were refractory to the growth-inhibiting effects of castration demonstrated by parental LNCaP cells. Data obtained in this study demonstrate that the bcl-2 oncoprotein can protect prostate cancer cells from apoptotic stimuli in vitro and suggest that such protection correlates with the ability to form hormone-refractory prostate tumors in vivo.