gebhart/patrepeval huggingface dataset:
processingin vitroof an abasic site reacted with methoxyamine: a new assay for the detection of abasic sites formedin vivo (1991)

In this study we demonstrate that the different substrate recognition properties of bacterial and human AP endonucleases might be used to quantify and localize apurinic (AP) sites formed in DNA in vivo. By using a model oligonucleotide containing a single AP site modified with methoxyamine (MX), we show that endonuclease III and IV of E. coli are able to cleave the alkoxyamine-adducted site whereas a partially purified HeLa AP endonuclease and crude cell-free extracts from HeLa cells are inhibited by this modification. In addition MX-modified AP sites in a DNA template retain their ability to block DNA synthesis in vitro. Since MX can efficiently react with AP sites formed in mammalian cells in vivo we propose that the MX modified abasic sites thus formed can be quantitated and localized at the level of the individual gene by subsequent site specific cleavage by either E. coli endonuclease III or IV in vitro.
Vaccination of cattle with outer membrane protein-enriched fractions of Pasteurella haemolytica and resistance against experimental challenge exposure. (1995)

Administration of an N-lauroylsarcosine-derived outer membrane protein fraction of Pasteurella haemolytica A1 (SCI-1) induced a protective response in calves against intrathoracic challenge exposure with the homologous serovar. Outer membrane proteins from heterologous serovars, A6 and A9, induced partial protection that was associated with their respective similarities to serovar A1 in outer membrane protein profiles derived by use of sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Calves vaccinated with SCI preparations did not have detectable neutralizing antibody to P haemolytica A1 leukotoxin. Antibodies to whole-cell antigens, carbohydrate-protein subunit antigen, and SCI-1 were associated with resistance, which indicates that protein antigens shared among cell surface, carbohydrate-protein subunit, and SCI preparations are immunogenic and enhance resistance to experimental challenge exposure.
Systemic Infusion of FLK1+ Mesenchymal Stem Cells Ameliorate Carbon Tetrachloride-Induced Liver Fibrosis in Mice (2004)

These results suggest that Flk1 mMSCs might initiate endogenous hepatic tissue regeneration, engraft into host liver in response to CCl(4) injury, and ameliorate its fibrogenic effects.
Penetration of dapsone into cerebrospinal fluid of patients with AIDS (1997)

It has been proposed that dapsone in combination with pyrimethamine could be used for prophylaxis of both Pneumocystis carinii pneumonia and encephalitis due to Toxoplasma gondii. Ten patients with AIDS undergoing lumbar puncture for diagnostic purposes were studied in order to assess the penetration of dapsone into CSF. Blood and CSF samples were obtained between 3 and 72 h following administration. Six patients had received oral dapsone for at least 1 month at the dosage regimen of 100 mg twice of three times weekly and four patients had received a single oral 100 mg dose. Dapsone concentration in CSF ranged from 0.013 to 0.296 mg/L while concentrations in plasma ranged from 0.018 to 1.231 mg/L. The CSF:plasma concentration ratio ranged from 0.21 to 2.01. The MIC of dapsone in combination with pyrimethamine against T. gondii is unknown, and further data are required to confirm whether the CSF concentrations of dapsone found in our study are sufficient to inhibit T. gondii growth in patients infected with human immunodeficiency virus (HIV). The high interpatient variability of dapsone CSF concentrations warrants further studies in selected categories of patients with HIV infection.
Correlation between stromelysin‐3 mRNA level and outcome of human breast cancer (1994)

The expression level of stromelysin-3 (ST3) mRNA was analyzed by in situ hybridization of formalin-fixed, paraffin-embedded primary breast-tumor samples from 76 patients. Digital image analysis of the dark-field in situ hybridization signal was used to measure the maximal level of ST3 expression in each tumor. All 55 invasive ductal carcinomas and 9 of 10 invasive lobular carcinomas were positive for ST3. Invasive tumors had significantly higher levels of ST3 than in situ tumors. Furthermore, ST3 levels were higher in invasive ductal carcinomas than in invasive lobular carcinomas. The ST3 expression level was significantly correlated to fatal metastatic disease (mean follow-up 104 months). ST3 levels of < 2,500 units were associated with distant metastasis in 46% of patients, whereas levels of > 2,500 units were associated with metastasis in 79% of patients selected for study. ST3 mRNA levels did not correlate with tumor size, microvessel density, DNA ploidy or estrogen-receptor levels. Studies of ST3 expression may provide information valuable for the understanding of breast cancer biology and for prognosis.
Classification and basic properties of contrast agents for magnetic resonance imaging (2009)

A comprehensive classification of contrast agents currently used or under development for magnetic resonance imaging (MRI) is presented. Agents based on small chelates, macromolecular systems, iron oxides and other nanosystems, as well as responsive, chemical exchange saturation transfer (CEST) and hyperpolarization agents are covered in order to discuss the various possibilities of using MRI as a molecular imaging technique. The classification includes composition, magnetic properties, biodistribution and imaging applications. Chemical compositions of various classes of MRI contrast agents are tabulated, and their magnetic status including diamagnetic, paramagnetic and superparamagnetic are outlined. Classification according to biodistribution covers all types of MRI contrast agents including, among others, extracellular, blood pool, polymeric, particulate, responsive, oral, and organ specific (hepatobiliary, RES, lymph nodes, bone marrow and brain). Various targeting strategies of molecular, macromolecular and particulate carriers are also illustrated.
Catabolic control of the enhanced alanine-preferring system for amino acid transport in glucose-starved hamster cells requires protein synthesis (1979)

In cultured hamster cells starved for glucose for 24 hr there is an enhancement of the rate of alpha-aminoisobutyric acid transport ("shiftup"). When the starved cells are re-fed with glucose, the rate of transport shifts back down to the low, "regulated" rate typical of cells continuously fed with medium containing glucose ("shiftdown"). The high, deregulated rate of transport is maintained, however, when cycloheximide is present for 24 hr during the re-feeding with glucose. Maintenance of the high transport rate is evident only when the cells are incubated in amino acid-free medium just prior to the transport assay or when the assays are conducted with isolated membrane vesicles. A premature, pseudoshiftdown was observed in intact cells within as little as 2 hr after re-feeding when care was not taken to deplete the amino acid pool prior to the transport assay. In addition, a cycloheximide-insensitive increase in transport was observed when cultures were re-fed for 2 hr with amino acid-free medium containing fresh serum. These results emphasize the often overlooked precautions that should be taken to guard against artifacts that could mislead interpretations of amino acid transport data. More important, however, is the finding that Na(+)-dependent amino acid transport in cultured animal cells is regulated in part by a factor (or factors) that becomes inactivated when the cells are maintained under nonglycolytic culture conditions. In order to reactivate the control mechanism, starved cells that have been re-fed with glucose must resynthesize the regulatory factor(s). Thus, in at least cultured hamster cells, Na(+)-dependent amino acid transport regulation is much like the hexose transport regulation in that catabolic control (shiftdown) requires protein synthesis.
Predicting Mortality Among Patients Hospitalized for Heart Failure (2003)

Among community-based heart failure patients, factors identifiable within hours of hospital presentation predicted mortality risk at 30 days and 1 year. The externally validated predictive index may assist clinicians in estimating heart failure mortality risk and in providing quantitative guidance for decision making in heart failure care.
Investigating a New Approach to Film Casting for Enhanced Drug Content Uniformity in Polymeric Films (2008)

Films prepared by conventional casting onto trays such as teflon-coated perspex trays (TCPTs) suffer from poor drug content uniformity. The aim of this study was to prepare a silicone-molded tray (SMT) with individual wells for film casting and to evaluate it in terms of enhancing drug content uniformity. Films were prepared by solvent evaporation or emulsification and cast onto TCPT and SMT. Preparation of films by the SMT method was superior in terms of meeting drug content uniformity requirements. As compared with the TCPT method, the SMT casting method also reduced the variability in mucoadhesivity, drug release, and film thickness. Reproducibility of the SMT method was demonstrated in terms of drug content, mucoadhesion, and drug release.
Adverse Events Associated With Nonablative Cutaneous Laser, Radiofrequency, and Light-Based Devices (2007)

Medical and esthetic indications and demand for nonablative laser and light-based treatments are increasing. Although these are generally safe procedures, laser practitioners should be aware of potential complications that may be associated with therapy. An adverse event may be defined as any undesirable effect, even if expected, that occurs with laser treatment. These adverse events can be related to patient factors, professional errors, common side effects, and more serious complications. A variety of providers, including nondermatologists, perform laser treatments and must be aware of therapeutic outcomes as well as potential complications after laser surgery. Clinical indications for nonablative laser treatments, common side effects, and more serious adverse events will be reviewed in addition to treatment and prevention of these potential complications.
Role of gut-enriched Krüppel-like factor in colonic cell growth and differentiation (2000)

Cancer cells differ from normal cells in many aspects, including hyperproliferation and loss of differentiation. Recent research has focused on the role of transcription factors in regulating abnormal cell growth. Gut-enriched Krüppel-like factor (GKLF) is a newly identified eukaryotic zinc finger protein expressed extensively in the gastrointestinal tract. In the current study, we demonstrated that GKLF mRNA levels were significantly decreased in the dysplastic epithelium of the colon, including adenomatous polyp and cancer. GKLF immunostains in the normal colon were higher at the surface epithelium and gradually decreased toward the crypt, but this gradient was not present in the adenomatous and cancerous mucosa. Constitutive overexpression of GKLF DNA in a human colonic adenocarcinoma cell line (HT-29) decreased [(3)H]thymidine incorporation, whereas suppression of GKLF gene increased DNA synthesis, indicating that downregulation of the GKLF gene might contribute to cellular hyperproliferation. Cyclin D1 (CD1) protein level and CD1-associated kinase activity were decreased in HT-29 cell overexpressed GKLF cDNA, and CD1 promoter activity was profoundly suppressed by GKLF. When HT-29 cells were cultured in the presence of sodium butyrate, GKLF mRNA levels increased as cells acquired more differentiated phenotypes. These results suggest that GKLF plays an important role in regulating cell growth and differentiation in the colonic epithelium and that downregulation of GKLF expression may cause colonic cells to become hyperproliferative. Furthermore, GKLF appears to be a transcriptional repressor of the CD1 gene.
INCREASED EXPRESSION OF IL‐15 IN THE SYNOVIUM OF PATIENTS WITH RHEUMATOID ARTHRITIS COMPARED WITH PATIENTS WITH YERSINIA‐INDUCED ARTHRITIS AND OSTEOARTHRITIS (1997)

Recently, a new player in the cytokine network has been described that is produced by monocytes and can be detected in the rheumatoid synovium: interleukin-15 (IL-15). Since this cytokine may play a role in the accumulation and activation of T-cells, B-cells, and natural killer (NK) cells characteristic of synovial tissue (ST) from patients with rheumatoid arthritis (RA), the expression of IL-15 was studied in ST from RA patients in comparison with ST from patients with reactive arthritis (ReA) and osteoarthritis (OA) and the phenotype of IL-15-positive cells was determined. IL-15 expression was investigated by immunohistochemical analysis of ST from ten patients with RA, ten patients with Yersinia enterocolitica-induced ReA, and nine patients with OA. The immunohistological findings were quantified and the results obtained in the different patient groups were compared. To determine the phenotype of IL-15-expressing cells, double-labelling immunofluorescence was performed. The expression of IL-15 was significantly higher in ST from patients with RA than in ST from patients with ReA or OA. In double-label experiments, co-expression was observed with markers for macrophages, T-cells, and NK cells. The composition of the cellular infiltrate in the synovium of patients with RA might be partly explained by the specific increase in expression of IL-15 in rheumatoid ST. It can be speculated that IL-15 production by inflammatory cells other than macrophages may occur in the rheumatoid synovium. © 1997 by John Wiley & Sons, Ltd.
[Azoles. Part 5: On halogen-nitroindazole derivatives and their antibacterial properties (author's transl)]. (1979)

The authors describe a modified procedure for the synthesis of the 3-halogenindazole derivatives 1--7 and of the 1-hydroxymethylindazole derivatives 8--14. The compounds 8--13 yield the corresponding 1-chloromethyl derivatives 15--20, and 23 is obtained from 3. The compounds 7--23 exert slight antibacterial effects.
On the Possibility of a Nuclear Mass-Energy Resonance in D + D Reactions at Low Energy (1989)

The possibility of a nuclear mass-energy resonance is offered to explain recent “cold fusion” results.
Stable Chloroplast Transformation of the Unicellular Red AlgaPorphyridium Species (2002)

Abstract Red algae are extremely attractive for biotechnology because they synthesize accessory photosynthetic pigments (phycobilins and carotenoids), unsaturated fatty acids, and unique cell wall sulfated polysaccharides. We report a high-efficiency chloroplast transformation system for the unicellular red microalgaPorphyridium sp. This is the first genetic transformation system for Rhodophytes and is based on use of a mutant form of the gene encoding acetohydroxyacid synthase [AHAS(W492S)] as a dominant selectable marker. AHAS is the target enzyme of the herbicide sulfometuron methyl, which effectively inhibits growth of bacteria, fungi, plants, and algae. Biolistic transformation of synchronized Porphyridium sp. cells with the mutant AHAS(W492S) gene that confers herbicide resistance gave a high frequency of sulfomethuron methyl-resistant colonies. The mutant AHAS gene integrated into the chloroplast genome by homologous recombination. This system paves the way for expression of foreign genes in red algae and has important biotechnological implications.
Chromatin cleavage in apoptosis: Association with condensed chromatin morphology and dependence on macromolecular synthesis (1984)

In glucocorticoid-treated rat thymocytes and the murine lymphoid cell lines L5178 and S49 the morphology of apoptosis is associated with chromatin cleavage. The cleavage is at internucleosomal sites, apparently through activation of an endogenous endonuclease. In variants of the cell lines selected for resistance to glucocorticoid, neither apoptosis nor chromatin cleavage were observed after steroid treatment, and steroid receptors were undetectable. In thymocytes, both the morphological changes of apoptosis and chromatin cleavage were inhibited by cycloheximide and actinomycin D. The calcium-magnesium ionophore A23187 induced apoptosis and chromatin cleavage in thymocytes, and these effects were also inhibited by cycloheximide. The data confirm that the condensed chromatin which characterizes apoptosis morphologically consists of endogenously digested chromatin fragments. They also provide support for the view that at least some cells enter apoptosis by a process dependent upon macromolecular synthesis.
Pancreatic cancer stem cells – insights and perspectives (2009)

There is increasing evidence that solid tumours, including pancreatic cancer, are hierarchically organized and sustained by a distinct subpopulation of CSC. Direct evidence for the CSC hypothesis has emerged from mouse models only recently. While the clinical relevance of CSC remains a fundamental issue, current findings suggest that specific targeting of these cells is possible and therapeutically relevant.
HRMAS1H-NMR measured changes of the metabolite profile as mesenchymal stem cells differentiate to targeted fat cellsin vitro: implications for non-invasive monitoring of stem cell differentiationin vivo (2008)

Mesenchymal stem cells (MSCs) have shown a great potential for clinical applications in regenerative medicine. However, it remains challenging to follow the transplanted cell grafts in vivo. Nuclear magnetic resonance spectroscopy (NMR or MRS) is capable of determining and quantifying the cellular metabolites in tissue and organs non-invasively, therefore it is an attractive method for monitoring and evaluating the differentiation and functions of transplanted stem cells in vivo. In this study, metabolic changes of MSCs undergoing adipogenic differentiation to targeted fat cells were investigated in vitro, using solid-state high-resolution magic angle spinning (1)H nuclear magnetic resonance spectroscopy. Quantification of metabolite concentrations before and after differentiation of MSCs showed decreased levels of intracellular metabolites, including choline, creatine, glutamate and myo-inositol, and a substantially increased level of fatty acids, when mesenchymal stem cells were differentiated preferentially to fat cells. Intracellular creatine, myo-inositol and choline reduced from 10.4 +/- 0.72, 16.2 +/- 1.2 and 8.22 +/- 0.51 mM to 3.27 +/- 0.34, 6.1 +/- 0.46 and 3.11 +/- 0.32 mM, respectively, while fatty acids increased from 32.6 +/- 1.5 to 91.2 +/- 3.2 mM after undergoing 3 weeks of differentiation. The increase of the fatty acid concentration measured by NMR is confirmed by the observation of 80% fat cells in differentiated cells by cell counting assay, suggesting resonances from fatty acids may be used as metabolite markers for monitoring MSC differentiation to fat cells in vivo, using the magnetic resonance spectroscopic technique readily available on MRI scanners.
Pharmacokinetics and pharmacodynamics of subcutaneous injection of long-acting human insulin analog glargine, NPH insulin, and ultralente human insulin and continuous subcutaneous infusion of insulin lispro. (2000)

To compare the pharmacokinetics/dynamics of the long-acting insulin analog glargine with NPH, ultralente, and continuous subcutaneous (SC) infusion of insulin lispro (continuous subcutaneous insulin infusion [CSII]), 20 C-peptide-negative type 1 diabetic patients were studied on four occasions during an isoglycemic 24-h clamp. Patients received SC injection of either 0.3 U/kg glargine or NPH insulin (random sequence, crossover design). On two subsequent occasions, they received either an SC injection of ultralente (0.3 U/kg) or CSII (0.3 U x kg(-1) x 24 h(-1)) (random sequence, crossover design). After SC insulin injection or CSII, intravenous (IV) insulin was tapered, and glucose was infused to clamp plasma glucose at 130 mg/dl for 24 h. Onset of action (defined as reduction of IV insulin >50%) was earlier with NPH (0.8 +/- 0.2 h), CSII (0.5 +/- 0.1 h), and ultralente (1 +/- 0.2 h) versus glargine (1.5 +/- 0.3 h) (P < 0.05) (mean +/- SE). End of action (defined as an increase in plasma glucose >150 mg/dl) occurred later with glargine (22 +/- 4 h) than with NPH (14 +/- 3 h) (P < 0.05) but was similar with ultralente (20 +/- 6 h). NPH and ultralente exhibited a peak concentration and action (at 4.5 +/- 0.5 and 10.1 +/- 1 h, respectively) followed by waning, whereas glargine had no peak but had a flat concentration/action profile mimicking CSII. Interindividual variability (calculated as differences in SD of plasma insulin concentrations and glucose infusion rates in different treatments) was lower with glargine than with NPH and ultralente (P < 0.05) but was similar with glargine and CSII (NS). In conclusion, NPH and ultralente are both peak insulins. Duration of action of ultralente is greater, but intersubject variability is also greater than that of NPH. Glargine is a peakless insulin, it lasts nearly 24 h, it has lower intersubject variability than NPH and ultralente, and it closely mimics CSII, the gold standard of basal insulin replacement.
Recognition of phage-expressed peptides containing Asx-Pro sequences by monoclonal antibodies produced against Plasmodium falciparum circumsporozoite protein (1997)

The immunodominant region of the Plasmodium falciparum circumsporozoite protein is comprised mainly of a series of tetrapeptide repeats that can, depending on the starting cadence chosen, be described as (NANP)n, (ANPN)n, (NPNA)n or (PNAN)n in one-letter amino acid code. Data from several studies suggest that the NPNA cadence alone is structurally correct, in that each NPNA tetrapeptide effectively forms a structural unit initiated by an Asx-Pro turn. To explore this idea further and to assess the immunological relevance of peptide conformation as it relates to the cadence of these tetrapeptide repeats, we used ELISA to compare the abilities of monoclonal antibodies (MAbs) produced against P. falciparum sporozoites to recognize repeat-related heptapeptides expressed on the surface of filamentous bacteriophage. Having included representatives of both NANP and NPNA cadences and other peptides in which the number and location of Asx-Pro sequences varied, we provide evidence that Asx-Pro sequences play an important role in peptide conformation and antibody recognition, that peptide conformation is influenced by the cadence of the tetrapeptide repeats and that peptide conformation is important to the abilities of these MAbs to recognize their epitopes.
[Analysis of the polymorphic alleles of genes encoding phase 1 and phase 2 detoxication enzymes in patients with endometriosis]. (2003)

Polymorphysms of the three genes encoding phase 1 (CYP1A1, mEPH1, and CYP2E2) and the three genes encoding phase 2 (NAT2, GSTM1, and GSTT1) xenobiotic detoxication enzymes were typed by use of PCR in 74 patients with extragenital endometriosis. Distribution of the CYP1A1, mEPHX1, CYP2E1, NAT2, and GSTM1 polymorphic alleles in the patient group corresponded to that in the control group. At the same time, functionally defective genotypes GSTM1 0/0, NAT2 S/S; GSTM1 0/0, GSTT1 0/0; and GSTT1 0/0, NAT2 S/S were three, four and eight times more frequent among the patients than in healthy individuals. This observation suggests the existence of a distinct association between the functionally defective alleles of the phase 2 xenobiotic detoxication and endometriosis. Possible mechanisms underlying this association are discussed. It is suggested that typing of the NAT2, GSTM1, and GSTT1 genes can be useful for the assessment of the predisposition to endometriosis.