gebhart/patrepeval huggingface dataset:
Antineoplastic agents 365. Dolastatin 10 SAR probes. (1998)

The remarkable anticancer drug dolastatin 10 (1a) from the Indian Ocean sea hare Dolabella auricularia is currently undergoing phase I clinical trials. Thirty-eight new structural modifications of this unusual peptide have been synthesized and evaluated against a variety of human and murine cancer cell lines, and for their ability to inhibit tubulin polymerization and vinblastine and GTP binding to tubulin. Dolastatin 10 and one structural modification was found to have antifungal activity, while one other structural modification of the parent compound exhibited antibacterial activity. Some of the new peptides approximated the antineoplastic potency of dolastatin 10, especially those based on replacement of the Doe unit with Met, Phe or an appropriately substituted phenylethylamide.
Insect immunity. Constitutive expression of a cysteine-rich antifungal and a linear antibacterial peptide in a termite insect. (2001)

Two novel antimicrobial peptides, which we propose to name termicin and spinigerin, have been isolated from the fungus-growing termite Pseudacanthotermes spiniger (heterometabole insect, Isoptera). Termicin is a 36-amino acid residue antifungal peptide, with six cysteines arranged in a disulfide array similar to that of insect defensins. In contrast to most insect defensins, termicin is C-terminally amidated. Spinigerin consists of 25 amino acids and is devoid of cysteines. It is active against bacteria and fungi. Termicin and spinigerin show no obvious sequence similarities with other peptides. Termicin is constitutively present in hemocyte granules and in salivary glands. The presence of termicin and spinigerin in unchallenged termites contrasts with observations in evolutionary recent insects or insects undergoing complete metamorphosis, in which antimicrobial peptides are induced in the fat body and released into the hemolymph after septic injury.
Animal models of rheumatoid arthritis and their relevance to human disease (2005)

Rodent models of rheumatoid arthritis (RA) are useful tools to study the pathogenic process of RA. Among the most widely used models of RA are the streptococcal cell wall (SCW) arthritis model and the collagen-induced arthritis (CIA). Both innate and adaptive immune mechanisms are involved in these rodent models. While no models perfectly duplicate the condition of human RA, they are easily reproducible, well defined and have proven useful for development of new therapies for arthritis, as exemplified by cytokine blockade therapies. Besides SCW and CIA models, there are numerous others including transgenic models such as K/BxN, induced models such as adjuvant-induced and pristane models, and spontaneous models in certain mouse strains, that have been used to help understand some of the underlying mechanisms. This review provides an update and analysis of RA models in mice and rats. The array of models has provided rheumatologists and immunologists a means to understand the multifactorial disease in humans, to identify new drug targets, and to test new therapies.
Real-Time Imaging of Fluorescent Flagellar Filaments (2000)

Bacteria swim by rotating flagellar filaments that are several micrometers long, but only about 20 nm in diameter. The filaments can exist in different polymorphic forms, having distinct values of curvature and twist. Rotation rates are on the order of 100 Hz. In the past, the motion of individual filaments has been visualized by dark-field or differential-interference-contrast microscopy, methods hampered by intense scattering from the cell body or shallow depth of field, respectively. We have found a simple procedure for fluorescently labeling cells and filaments that allows recording their motion in real time with an inexpensive video camera and an ordinary fluorescence microscope with mercury-arc or strobed laser illumination. We report our initial findings with cells of Escherichia coli. Tumbles (events that enable swimming cells to alter course) are remarkably varied. Not every filament on a cell needs to change its direction of rotation: different filaments can change directions at different times, and a tumble can result from the change in direction of only one. Polymorphic transformations tend to occur in the sequence normal, semicoiled, curly 1, with changes in the direction of movement of the cell body correlated with transformations to the semicoiled form.
Creating and parameterizing patient-specific deep brain stimulation pathway-activation models using the hyperdirect pathway as an example (2017)

Parameterization of patient-specific DBS models can be highly detailed and constrained, thereby providing confidence in the simulation predictions, but at the expense of time demanding technical implementation steps. DBS PAMs represent new tools for investigating possible correlations between brain pathway activation patterns and clinical symptom modulation.
Combination of retinoic acid and ursodeoxycholic acid attenuates liver injury in bile duct-ligated rats and human hepatic cells (2010)

Our findings indicate that the addition of RA to UDCA reduces the bile salt pool size and liver fibrosis and might be an effective supplemental therapy with UDCA for cholestatic diseases.
Survey on Needs of Youth and Young Adults with HIV in Malaysia (2012)

This project report is based on a face-to-face interview with 477youths and young adults with HIV from four major HIV treatmentcentres in Malaysia. The qualitative study was designed toassess the treatment, care and support services received bythese young PLHIV (People Living with HIV) and assess theirphysical and psychosocial needs and sexual issues.
Multi-Copper Oxidases (1997)

Earlier times in multi-copper oxidase research versus recent results from Goteborg, B. Malmstrom spatial structures of the multi-copper oxidases ascorbate oxidase, laccase and related proteins - implications for the catalytic mechanism, A. Messerschmidt the structure of human ceruloplasmin at 3.1 A resolution, P.F. Lindley et al spectroscopy of multi-copper oxidases, E.I. Solomon et al bioinorganic chemistry of laccase, D.R. McMillin and M.K. Egglestone kinetic studies on polyporous and tree laccases, B. Reinhammar fungal laccases - role in delignification and possible industrial applications, M. Smith et al spectroscopy of cucumber ascorbate oxidase and fungal laccase, T. Sakurai and D. Suzuki biological function and enzyme kinetics of ascorbate oxidase, L. Avigliano and A. Finazzi-Agro the biology of human ceruloplasmin, Z.L. Harris et al molecular properties of ceruloplasmin from different species, L. Calabrese and C. Musci electron transfer reactions in multi-copper oxidases, O. Farver and I. Pecht redox properties of blue multi-copper oxidases, P.M.H. Kroneck model compounds for multi-copper oxidases, P. Chaudhuri 199mHg-derivatives of laccase and ascorbate oxidase - a hyperfine spectroscopic study, T. Butz and W. Troger.
Vector contour representation for object recognition in neural networks (2003)

The authors introduce a new method of describing object features for neural network based classification. The angle information between boundary pixels of the binary image of an object is extracted and preprocessed to form the vector contour representation (VCR). The VCRs of different objects are then used for pattern classification. The Euclidean distance between two VCRs is used as the similarity measure during classification. Scaling- and translation-invariant object recognition can be achieved. Partial or complete rotation invariance can also be obtained if desired. The usefulness of the vector contour representation for object recognition is demonstrated through the test results.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Pharmacokinetics and pharmacodynamics of propranolol in hypertensive patients after sublingual administration: systemic availability (1998)

The bioavailability of propranolol depends on the degree of liver metabolism. Orally but not intravenously administered propranolol is heavily metabolized. In the present study we assessed the pharmacokinetics and pharmacodynamics of sublingual propranolol. Fourteen severely hypertensive patients (diastolic blood pressure (DBP) > or = 115 mmHg), aged 40 to 66 years, were randomly chosen to receive a single dose of 40 mg propranolol hydrochloride by sublingual or peroral administration. Systolic (SBP) and diastolic (DBP) blood pressures, heart rate (HR) for pharmacodynamics and blood samples for noncompartmental pharmacokinetics were obtained at baseline and at 10, 20, 30, 60 and 120 min after the single dose. Significant reductions in BP and HR were obtained, but differences in these parameters were not observed when sublingual and peroral administrations were compared as follows: SBP (17 vs 18%, P = NS), DBP (14 vs 8%, P = NS) and HR (22 vs 28%, P = NS), respectively. The pharmacokinetic parameters obtained after sublingual or peroral drug administration were: peak plasma concentration (CMAX): 147 +/- 72 vs 41 +/- 12 ng/ml, P < 0.05; time to reach CMAX (TMAX): 34 +/- 18 vs 52 +/- 11 min, P < 0.05; biological half-life (t1/2b): 0.91 +/- 0.54 vs 2.41 +/- 1.16 h, P < 0.05; area under the curve (AUCT): 245 +/- 134 vs 79 +/- 54 ng h-1 ml-1, P < 0.05; total body clearance (CLT/F): 44 +/- 23 vs 26 +/- 12 ml min-1 kg-1, P = NS. Systemic availability measured by the AUCT ratio indicates that extension of bioavailability was increased 3 times by the sublingual route. Mouth paresthesia was the main adverse effect observed after sublingual administration. Sublingual propranolol administration showed a better pharmacokinetic profile and this route of administration may be an alternative for intravenous or oral administration.
Digoxin inhibits retinal ischemia‐induced HIF‐1α expression and ocular neovascularization (2010)

Digoxin and other cardiac glycosides inhibit hypoxia-inducible factor-1 (HIF-1) transcriptional activity in cultured cells and suppress tumor xenograft growth. We tested the hypothesis that digoxin reduces HIF-1 levels in ischemic tissue in vivo and suppresses neovascularization. Well-established murine models of ocular neovascularization were used to test our hypothesis. In mice with ischemic retinopathy, intraocular or intraperitoneal injection of digoxin markedly reduced retinal levels of HIF-1alpha protein and mRNAs encoding multiple hypoxia-regulated proangiogenic proteins and their receptors. Daily intraperitoneal injection of 2 mg/kg starting at postnatal day (P) 12 or a single intravitreous injection of 100 ng of digoxin at P12 reduced retinal neovascularization by >70% at P17. Digoxin also reduced the number of CXCR4(+) cells and F4/80(+) macrophages in ischemic retina and significantly reduced choroidal neovascularization at Bruch's membrane rupture sites. Digoxin suppresses retinal and choroidal neovascularization by reducing HIF-1alpha levels, which blocks several proangiogenic pathways. Since digoxin suppresses multiple pathways in addition to VEGF signaling, it may provide advantages over specific VEGF antagonists for treatment of patients with retinal and choroidal diseases complicated by neovascularization and/or excessive vascular permeability. It may also be useful for treatment of neovascular diseases in other tissues.
Function of the human T-cell leukemia virus type 1 21-base-pair repeats in basal transcription (1997)

The human T-cell leukemia virus type 1 (HTLV-1) promoter contains three copies of an imperfect 21-bp repeat called Tax-responsive element (TRE1). To examine the role of individual TRE1 sequences in basal transcription of the HTLV-1 promoter, site-directed mutations were generated in all possible combinations of one, two, or all three TRE1 elements in the viral long terminal repeat (LTR) and tested in vivo for transcriptional activity. Mutation of the middle TRE1 resulted in the greatest reduction in basal activity. Electrophoretic mobility shift analysis demonstrated that the protein complexes bound to each of the three TRE1 sequences were not identical. The complexes formed with the TATA-distal and middle TRE1s were dependent on the core cyclic AMP response element (CRE) found in all three TRE1s, while the cellular transcription factor Sp1 bound the TATA-proximal TRE1 in a CRE-independent manner. Sp1 binding produced a footprint on the viral LTR which covered the 5' region of the proximal TRE1. Mixing experiments demonstrated that the bindings of CREB and Sp1 to the proximal TRE1 were mutually exclusive. Sp1 was able to activate transcription both from the complete LTR and from the proximal TRE1 alone. These studies demonstrate that the TRE1 elements in the HTLV-1 LTR are functionally nonequivalent and suggest that Sp1 can influence HTLV-1 basal transcription.
Inhibition of initiator‐induced SV40 gene amplification in SV40‐transformed Chinese hamster cells by infection with a defective parvovirus (1983)

Amplification of SV40 genes in SV40-transformed Chinese hamster embryo cells (CO631) by chemical carcinogens as well as by herpes simplex virus infection can be inhibited by infection with the defective parvovirus, AAV-5. This is shown by in situ hybridization with SV40 DNA of AAV-5-infected CO631 cells after treatment with herpes simplex virus type 1 or with chemical carcinogens: the initiator-induced selective amplification of SV40 sequences is prevented in the presence of the parvovirus. During HSV-infection and also in the presence of carcinogens, in CO631 cells parvovirus DNA is synthesized and AAV-5-specific antigens are expressed as revealed by hybridization with cloned AAV-5 DNA or by immunofluorescence with monoclonal antibodies, respectively. The inhibition of initiator-induced gene amplification could point to the mechanism of parvovirus-mediated inhibition of tumor development and may indicate an important role of selective gene amplification in oncogenesis.
Internalisation enhances photo-induced cytotoxicity of monoclonal antibody-phthalocyanine conjugates (2001)

Immunophototherapy of cancer combines the specificity of a monoclonal antibody (MAb) to an overexpressed tumor marker with the phototoxic properties of the conjugated dye. To analyze the potential role of internalisation of the dye on photo-induced cytotoxicity, we compared two target antigens, carcinoembryonic antigen (CEA) that does not internalise and ErbB2 that does. Human ovarian carcinoma SKOv3 cells that express a high level of ErbB2 were transfected with the CEA cDNA. Using FACS analysis, the resulting cell line, SKOv3-CEA-1B9, demonstrated comparable levels of expression of the two target antigens. Aluminium tetrasulfophthalocyanine (AlPcS(4)) was covalently coupled to anti-CEA MAb 35A7, anti-ErbB2 MAb FSP77 and a non-specific MAb PX, via a five-carbon sulfonamide spacer chain (A(1)) at molar ratios ranging from 6 to 9 moles of AlPcS(4) per mole of MAb. The 35A7-(AlPcS(4)A(1))(8) conjugate induced 68% growth inhibition of the SKOv3-CEA-1B9 cell line after a 20 h incubation at 2.50 microg/ml (based on AlPcS(4)A(1) content) following light exposure. However, the FSP77-(AlPcS(4)A(1))(6) conjugate gave a 51% growth inhibition for an AlPcS(4)A(1) concentration as low as 0.04 microg/ml after the same incubation time and exposure to the same light dose. At a 1.25 microg/ml AlPcS(4)A(1) concentration, the FSP77-(AlPcS(4)A(1))(6) conjugate gave a 67% growth inhibition after an incubation time as short as 1 h, reaching a 96% inhibition after an 8 h incubation time. Using an unique cell line that expresses two different target antigens, we demonstrated a clear advantage of an internalising over a non-internalising MAb-dye conjugate in terms of phototoxic efficacy. In vivo evaluation of the photodynamic properties of the conjugates is in progress.
Semi–Selective Fatty Acyl Reductases from Four Heliothine Moths Influence the Specific Pheromone Composition (2012)

We conclude that a pgFAR with broad specificity is involved in heliothine moth pheromone biosynthesis, functioning as a semi-selective funnel that produces species-specific alcohol product ratios depending on the fatty-acyl precursor ratio in the pheromone gland. This study further supports the key role of these in pheromone biosynthesis and emphasizes the interplay between the pheromone fatty acyl precursors and the Lepidoptera specific pgFARs in shaping the pheromone composition.
Inverse relation between serum cotinine concentration and blood pressure in cigarette smokers. (1989)

Blood pressure is, on average, lower in cigarette smokers than in nonsmokers. In a cross-sectional study of 288 normotensive bus drivers, we found a significant inverse correlation between serum cotinine (the major metabolite of nicotine) and systolic and diastolic blood pressure that could not be accounted for by age, body weight, or alcohol consumption. Over the observed range of cotinine values, the average decrease in blood pressure was 10.7 and 7.0 mm Hg for systolic and diastolic blood pressures, respectively. We suggest that cotinine be measured to assess the influence of cigarette smoking in epidemiologic studies of blood pressure.
The Role of Growth Factor Receptor Pathways in Human Breast Cancer Cells Adapted to Long-term Estrogen Deprivation (2005)

To study the long-term effects of estrogen deprivation on breast cancer, MCF-7Ca human estrogen receptor-positive breast cancer cells stably transfected with human aromatase gene were cultured in the steroid-depleted medium for 6 to 8 months until they had acquired the ability to grow. Proliferation of these cells (UMB-1Ca) was accompanied by increased expression of human epidermal growth factor receptor 2, increased activation of AKT through phosphorylation at Ser473 and Thr308, and increased invasion compared with parental MCF-7Ca cells. Estrogen receptor expression was also increased 5-fold. Although growth was inhibited by the antiestrogen fulvestrant, the IC50 was 100-fold higher than for parental MCF-7Ca cells. Aromatase inhibitor letrozole also inhibited growth at 10,000-fold higher concentration than required for MCF-7Ca cells, whereas anastrozole, exemestane, formestane, and tamoxifen were ineffective at 100 nmol/L. Growth of UMB-1Ca cells was inhibited by phosphatidylinositol 3-kinase inhibitor wortmannin (IC50 approximately 25 nmol/L) and epidermal growth factor receptor kinase inhibitor gefitinib (ZD 1839; IC50 approximately 10 micromol/L) whereas parental MCF-7Ca cells were insensitive to these agents. Concomitant treatment of UMB-1Ca cells with the signal transduction inhibitors and anastrozole and tamoxifen restored their growth inhibitory effects. These studies show that estrogen deprivation results in up-regulation of growth factor signaling pathways, which leads to a more aggressive and hormone refractory phenotype. Cross-talk between ER and growth factor signaling was evident as inhibition of these pathways could restore estrogen responsiveness to these cells.
Biology of disease: free radicals and tissue injury. (1982)

A free radical is any molecule that has an odd number of electrons. Free radicals, which can occur in both organic (i.e., quinones) and inorganic molecules (i.e., O(2)), are highly reactive and, therefore, transient. Free radicals are generated in vivo as by products of normal metabolism. They are also produced when an organism is exposed to ionizing radiation, to drugs capable of redox cycling, or to xenobiotics that can form free radical metabolites in situ. Cellular targets at risk from free radical damage depend on the nature of the radical and its site of generation. In this review we survey cellular sources of free radicals and the reactions they can undergo and discuss cellular defenses and adaptive mechanisms.
HEAVY METAL–INDUCED OXIDATIVE STRESS IN ALGAE1 (2003)

Heavy metals, depending on their oxidation states, can be highly reactive and, as a consequence, toxic to most organisms. They are produced by an expanding variety of anthropogenic sources suggesting an increasingly important role for this form of pollution. The toxic effect of heavy metals appears to be related to production of reactive oxygen species (ROS) and the resulting unbalanced cellular redox status. Algae respond to heavy metals by induction of several antioxidants, including diverse enzymes such as superoxide dismutase, catalase, glutathione peroxidase and ascorbate peroxidase, and the synthesis of low molecular weight compounds such as carotenoids and glutathione. At high, or acute, levels of metal pollutants, damage to algal cells occurs because ROS levels exceed the capacity of the cell to cope. At lower, or chronic, levels algae accumulate heavy metals and can pass them on to organisms of other trophic levels such as mollusks, crustaceans, and fishes. We review here the evidence linking metal accumulation, cellular toxicity, and the generation of ROS in aquatic environments.
Mapping the membrane proteome of Corynebacterium glutamicum (2005)

In order to avoid the specific problems with intrinsic membrane proteins in proteome analysis, a new procedure was developed which is superior to the classical two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) method in terms of intrinsic membrane proteins. For analysis of the membrane proteome from Corynebacterium glutamicum, we replaced the first separation dimension, i.e., the isoelectric focusing step, by anion-exchange chromatography, followed by sodium dodecyl sulfate (SDS)-PAGE in the second separation dimension. Enrichment of the membrane intrinsic subproteome was achieved by washing with 2.5 M NaBr which removed more than 35% of the membrane-associated soluble proteins. For the extraction and solubilization of membrane proteins, the detergent amidosulfobetaine 14 (ASB-14) was most efficient in a detailed screening procedure and proved also suitable for chromatography. 356 gel bands were spotted, and out of 170 different identified proteins, 50 were membrane-integral. Membrane proteins with one up to 13 transmembrane helices were found. Careful analysis revealed that this new procedure covers proteins from a wide pI range (3.7-10.6) and a wide mass range of 10-120 kDa. About 50% of the identified membrane proteins belong to various functional categories like energy metabolism, transport, signal transduction, protein translocation, and proteolysis while for the others a function is not yet known, indicating the potential of the developed method for elucidation of membrane proteomes in general.
Plant Products as Antimicrobial Agents (1999)

The use of and search for drugs and dietary supplements derived from plants have accelerated in recent years. Ethnopharmacologists, botanists, microbiologists, and natural-products chemists are combing the Earth for phytochemicals and "leads" which could be developed for treatment of infectious diseases. While 25 to 50% of current pharmaceuticals are derived from plants, none are used as antimicrobials. Traditional healers have long used plants to prevent or cure infectious conditions; Western medicine is trying to duplicate their successes. Plants are rich in a wide variety of secondary metabolites, such as tannins, terpenoids, alkaloids, and flavonoids, which have been found in vitro to have antimicrobial properties. This review attempts to summarize the current status of botanical screening efforts, as well as in vivo studies of their effectiveness and toxicity. The structure and antimicrobial properties of phytochemicals are also addressed. Since many of these compounds are currently available as unregulated botanical preparations and their use by the public is increasing rapidly, clinicians need to consider the consequences of patients self-medicating with these preparations.
Phosphorylation of myosin in non‐muscle and smooth muscle cells (1986)

Reversible phosphorylation of myosin subunits is observed in almost all eukaryotic cells. The data concerning sites and effects of phosphorylation on actin-activated ATPase activity of myosin and on its filament formation are described. These observations are discussed in terms of possible evolutionary trends and rules which may govern the process of myosin phosphorylation.