gebhart/patrepeval huggingface dataset:
The role of the macrophage in wound repair. A study with hydrocortisone and antimacrophage serum. (1975)

The role of the monocyte/macrophage in wound repair has been investigated by studying the healing process in wounds depleted of this cell and/or its phagocytic activity. Hydrocortisone acetate (0.6 mg/g body weight) administered as a subcutaneous depot was used to induce a prolonged monocytopenia in guinea pigs, and antimacrophage serum (AMS) was used for local elimination of tissue macrophages. In vitro, the presence of complement, macrophages are rapidly lysed and used killed by AMS. In the absence of complement, AMS is not cytotoxic but potently inhibits adherence to and phagocytosis of opsonized erythrocytes by macrophages. AMS titers were obtained by observation of adherence and phagocytosis of opsonized erythrocytes in serial dilutions of AMS. Six groups of animals were studied: a) untreated animals, b)animals receiving daily subcutaneous injections of normal rabbit serum (NRS) around each wound, c)animals receiving daily subcutaneous AMS around each wound, d)animals receiving systemic hydrocortisone, e)animals receiving systemic hydrocortisone and daily injections of NRS around each wound, and f)animals receiving systemic hydrocortisone and daily AMS around each wound. Wounds consisted of a series of six linear incisions in the dorsal skin. Subcutaneous AMS alone has no effect on the number of circulating monocytes, nor was there any observable effect on the number or the phagocytic ability of wound macrophages. Fibrosis in these wounds was unaffected. Systemic hydrocortisone induced a prolonged monocytopenia. The macrophage level in the wounds of these monocytopenic animals was reduced to approximately one-third that of controls; the phagocytic activity of the monocytes/macrophages that did appear in these wounds was, however, similar to that of controls. Some inhibition of wound debridement was observed in these wounds, but fibrosis was virtually unaffected. Collagen synthesis, as judged morphometrically, was similar to that of control wounds at all stages of repair. Conjoint systemic hydrocortisone and subcutaneous AMS around each wound resulted in the almost complete disappearance of macrophages from the wounds. Wound fibrin levels were elevated, and clearance of fibrin, neutrophils, erythrocytes and other miscellaneous debris from these wounds was delayed. Fibroblasts, which in control wounds first appear by 3 days postwounding and reach maximal levels by day 5, did not appear in these wounds until day 5, and their subsequent rate of proliferation was slower than that of controls. Continued.
Similar Patterns of Mitochondrial Vulnerability and Rescue Induced by Genetic Modification of α-Synuclein, Parkin, and DJ-1 in Caenorhabditis elegans (2005)

How genetic and environmental factors interact in Parkinson disease is poorly understood. We have now compared the patterns of vulnerability and rescue of Caenorhabditis elegans with genetic modifications of three different genetic factors implicated in Parkinson disease (PD). We observed that expressing alpha-synuclein, deleting parkin (K08E3.7), or knocking down DJ-1 (B0432.2) or parkin produces similar patterns of pharmacological vulnerability and rescue. C. elegans lines with these genetic changes were more vulnerable than nontransgenic nematodes to mitochondrial complex I inhibitors, including rotenone, fenperoximate, pyridaben, or stigmatellin. In contrast, the genetic manipulations did not increase sensitivity to paraquat, sodium azide, divalent metal ions (Fe(II) or Cu(II)), or etoposide compared with the nontransgenic nematodes. Each of the PD-related lines was also partially rescued by the antioxidant probucol, the mitochondrial complex II activator, D-beta-hydroxybutyrate, or the anti-apoptotic bile acid tauroursodeoxycholic acid. Complete protection in all lines was achieved by combining d-beta-hydroxybutyrate with tauroursodeoxycholic acid but not with probucol. These results show that diverse PD-related genetic modifications disrupt the mitochondrial function in C. elegans, and they raise the possibility that mitochondrial disruption is a pathway shared in common by many types of familial PD.
Engineering the isobutanol biosynthetic pathway in Escherichia coli by comparison of three aldehyde reductase/alcohol dehydrogenase genes (2009)

Biofuels synthesized from renewable resources are of increasing interest because of global energy and environmental problems. We have previously demonstrated production of higher alcohols from Escherichia coli using a 2-keto acid-based pathway. Here, we have compared the effect of various alcohol dehydrogenases (ADH) for the last step of the isobutanol production. E. coli has the yqhD gene which encodes a broad-range ADH. Isobutanol production significantly decreased with the deletion of yqhD, suggesting that the yqhD gene on the genome contributed to isobutanol production. The adh genes of two bacteria and one yeast were also compared in E. coli harboring the isobutanol synthesis pathway. Overexpression of yqhD or adhA in E. coli showed better production than ADH2, a result confirmed by activity measurements with isobutyraldehyde.
Delineation of antigen-specific and antigen-nonspecific CD8+ memory T-cell responses after cytokine-based cancer immunotherapy (2012)

Memory T cells exhibit tremendous antigen specificity within the immune system and accumulate with age. Our studies reveal an antigen-independent expansion of memory, but not naive, CD8(+) T cells after several immunotherapeutic regimens for cancer resulting in a distinctive phenotype. Signaling through T-cell receptors (TCRs) or CD3 in both mouse and human memory CD8(+) T cells markedly up-regulated programmed death-1 (PD-1) and CD25 (IL-2 receptor α chain), and led to antigen-specific tumor cell killing. In contrast, exposure to cytokine alone in vitro or with immunotherapy in vivo did not up-regulate these markers but resulted in expanded memory CD8(+) T cells expressing NKG2D, granzyme B, and possessing broadly lytic capabilities. Blockade of NKG2D in mice also resulted in significantly diminished antitumor effects after immunotherapy. Treatment of TCR-transgenic mice bearing nonantigen expressing tumors with immunotherapy still resulted in significant antitumor effects. Human melanoma tissue biopsies obtained from patients after topically applied immunodulatory treatment resulted in increased numbers of these CD8(+) CD25(-) cells within the tumor site. These findings demonstrate that memory CD8(+) T cells can express differential phenotypes indicative of adaptive or innate effectors based on the nature of the stimuli in a process conserved across species.
Plant cis-acting regulatory DNA elements (PLACE) database: 1999 (1999)

PLACE (http://www.dna.affrc.go.jp/htdocs/PLACE/) is a database of nucleotide sequence motifs found in plant cis-acting regulatory DNA elements. Motifs were extracted from previously published reports on genes in vascular plants. In addition to the motifs originally reported, their variations in other genes or in other plant species in later reports are also compiled. Documents for each motif in the PLACE database contains, in addition to a motif sequence, a brief definition and description of each motif, and relevant literature with PubMed ID numbers and GenBank accession numbers where available. Users can search their query sequences for cis-elements using the Signal Scan program at our web site. The results will be reported in one of the three forms. Clicking the PLACE accession numbers in the result report will open the pertinent motif document. Clicking the PubMed or GenBank accession number in the document will allow users to access to these databases, and to read the of the literature or the annotation in the DNA database. This report summarizes the present status of this database and available tools.
Effects of ABO and FUT2 genetic transcription absence on ABH histo-blood group antigen expression in lung cancer patients. (2011)

Expression of A/B/H blood group antigens was not detected in lung cancer tissues, which may have resulted from down-regulation of ABO/FUT2 gene transcription. Furthermore, the FUT2 gene may indirectly regulate expression of A/B blood group antigens by influencing H antigen expression.
Cross-linking of the CAMPATH-1 antigen (CD52) triggers activation of normal human T lymphocytes (1995)

The CAMPATH-1 (CD52) antigen is a 21-28 kDa glycopeptide which is highly expressed on lymphocytes and macrophages and is coupled to the membrane by a glycosylphosphatidylinositol (GPI) anchoring structure. The function of this molecule is unknown. However, it is an extremely good target for complement-mediated attack and antibody-mediated cellular cytotoxicity. The humanized CAMPATH-1H antibody, which is directed against CD52, is very efficient at mediating lymphocyte depletion in vivo, and is currently being used in clinical trials for lymphoid malignancy and rheumatoid arthritis. It is therefore important to examine the functional effects of this antibody on different lymphocyte sub-populations. Because several other GPI-linked molecules expressed on the surface of T lymphocytes are capable of signal transduction resulting in cell proliferation, we have investigated whether the CAMPATH-1 antigen can also mediate these effects. In the presence of phorbol esters and cross-linking anti-Ig antibodies, mAbs specific for CD52 induced proliferation and lymphokine production in highly purified resting CD4+ and CD8+ T lymphocytes. The rat IgG2c YTH 361.10 anti-CD52 antibody, however, was able to activate resting CD4+ and CD8+ T cells directly without cross-linking or phorbol myristate acetate in the absence of Fc-bearing cells. Anti-CD52 antibodies also augmented the anti-CD3 mediated proliferative response of CD4+ and CD8+ T cells when the two antibodies were co-immobilized onto the same surface or cross-linked in solution by the same second antibody. Both CD4+ CD45RA and CD4+ CD45RO T cells were stimulated to proliferate by anti-CD52 antibodies in the presence of appropriate co-stimulatory factors. Anti-CD52 mAbs did not, however, synergize with anti-CD2 or CD28 mAb to induce CD4+ T cell proliferation. The activation of CD4+ T cells by anti-CD52 antibodies was inhibited by cyclosporin A, suggesting a role for the calcineurin-dependent signal transduction pathways. Although CD52 could transduce a signal in T cells, anti-CD52 antibodies did not inhibit antigen-specific or polyclonal T cell responses, suggesting this molecule does not play an essential co-stimulatory role in normal T cell activation.
The Potential for Airborne Dispersal of Clostridium difficile from Symptomatic Patients (2010)

BACKGROUND. The high transmissibility and widespread environmental contamination by Clostridium difficile suggests the possibility of airborne dissemination of spores. We measured airborne and environmental C. difficile adjacent to patients with symptomatic C. difficile infection (CDI). METHODS. We conducted air sampling adjacent to 63 patients with CDI for 180 h in total and for 101 h in control settings. Environmental samples were obtained from surfaces adjacent to the patient and from communal areas of the ward. C. difficile isolates were characterized by ribotyping and multilocus variable-number tandem-repeat analysis to determine relatedness. RESULTS. Of the first 50 patients examined (each for 1 h), only 12% had positive air samples, most frequently those with active symptoms of CDI (10%, vs 2% for those with no symptoms). We intensively sampled the air around 10 patients with CDI symptoms, each for 10 h over 2 days, as well as a total of 346 surface sites. C. difficile was isolated from the air in the majority of these cases (7 of 10 patients tested) and from the surfaces around 9 of the patients; 60% of patients had both air and surface environments that were positive for C. difficile. Molecular characterization confirmed an epidemiological link between airborne dispersal, environmental contamination, and CDI cases. CONCLUSIONS. Aerosolization of C. difficile occurs commonly but sporadically in patients with symptomatic CDI. This may explain the widespread dissemination of epidemic strains. Our results emphasize the importance of single-room isolation as soon as possible after the onset of diarrhea to limit the dissemination of C. difficile.
Effect of Reducing Brain Glutamine Synthesis on Metabolic Symptoms of Hepatic Encephalopathy (1993)

Liver failure, or shunting of intestinal blood around the liver, results in hyperammonemia and cerebral dysfunction. Recently it was shown that ammonia caused some of the metabolic signs of hepatic encephalopathy only after it was metabolized by glutamine synthetase in the brain. In the present study, small doses of methionine sulfoximine, an inhibitor of cerebral glutamine synthetase, were given to rats either at the time of portacaval shunting or 3-4 weeks later. The effects on several characteristic cerebral metabolic abnormalities produced by portacaval shunting were measured 1-3 days after injection of the inhibitor. All untreated portacaval-shunted rats had elevated plasma and brain ammonia concentrations, increased brain glutamine and tryptophan content, decreased brain glucose consumption, and increased permeability of the blood-brain barrier to tryptophan. All treated rats had high ammonia concentrations, but the brain glutamine content was normal, indicating inhibition of glutamine synthesis. One day after shunting and methionine sulfoximine administration, glucose consumption, tryptophan transport, and tryptophan brain content remained near control values. In the 3-4-week-shunted rats, which were studied 1-3 days after methionine sulfoximine administration, the effect was less pronounced. Brain glucose consumption and tryptophan content were partially normalized, but tryptophan transport was unaffected. The results agree with our earlier conclusion that glutamine synthesis is an essential step in the development of cerebral metabolic abnormalities in hyperammonemic states.
Cephalosporin Derivatives of Doxorubicin as Prodrugs for Activation by Monoclonal Antibody-.beta.-Lactamase Conjugates (1995)

The synthesis of a series of cephalosporin doxorubicin derivatives that differ with respect to the substituent at position 7 of the cephem nucleus is described. These compounds are designed as prodrugs of doxorubicin for activation by monoclonal antibody-beta-lactamase conjugates. The key step in the synthesis of this series of compounds involves the use of the phenylacetamido group as an enzymatically removable protecting group for the 7-amino group on the cephem. In vitro cytotoxicity assays with H2981 lung adenocarcinoma cells revealed that cephalosporin doxorubicin derivatives were all less toxic than the released drug. Prodrugs containing negatively charged groups in the side chain, such as the delta-carboxybutanamido derivative 4 and the alpha-sulfophenylacetyl derivative 5, displayed the least cytotoxic activity and were 46- and 26-fold less toxic than doxorubicin, respectively. The efficiency of activation of all the prodrugs was evaluated in cytotoxicity assays on H2981 cells with the beta-lactamases from Enterobacter cloacae P99, Escherichia coli TEM-1, and Bacillus cereus (type II). In general, the E. cloacae enzyme was found to most rapidly activate the majority of these prodrugs. Phenylacetamido prodrug 2 and delta-carboxybutanamido prodrug 4 were both activated in an immunospecific manner by L6-E. cloacae beta-lactamase, a monoclonal antibody conjugate that binds to receptors on H2981 lung adenocarcinoma cells.
Responsiveness to transforming growth factor-beta (TGF-beta) restored by genetic complementation between cells defective in TGF-beta receptors I and II (1991)

Selection of mutant MvlLu mink lung epithelial cells resistant to growth inhibition by transforming growth factor-@ (TGF-@) has led to the isolation of cell clones with distinct alterations in type I and I1 TGF-@ receptors.Certain mutant clones present a decreased number or complete loss of detectable type I receptor.Other clones show a loss and/or altered electrophoretic mobility of the type I1 receptor, with concomitant loss of the type I receptor.Using somatic cell hybridization analysis we demonstrate the recessive nature of these mutants with respect to the wild-type phenotype and define various mutant complementation groups.Among these, hybrids between cells that express only type I1 receptor (R mutants) and cells that express neither receptor type (DRa mutants) rescue wild-type expression of type I receptors.Moreover, these hybrids regain full responsiveness to TGF-81, as measured by inhibition of DNA synthesis as well as stimulation of fibronectin and plasminogen activator inhibitor-1 production.These results provide evidence for an interaction between TGF-@ receptor components I and I1 and show that, in MvlLu cells, expression of both receptor types is required for mediation of biological responses to TGF-Bl.The transforming growth factor-0 (TGF-0)' family includes several homologous polypeptides that act in a paracrine fashion to regulate proliferation, differentiation, and other functions of the cell (1,2).The mammalian homodimeric isoforms TGF-01, -02, and $33, and the heterodimer TGF-01.2bind with high affinity to a set of cell surface proteins that include the type I receptor, the type I1 receptor, and betaglycan (2).Receptor types I and I1 are cell surface glycoproteins of 53 and 70 kDa, respectively.They are expressed ubiquitously,
A comparative study on the hypouricemic activity and potency in renal xanthine calculus formation of two xanthine oxidase/xanthine dehydrogenase inhibitors: TEI-6720 and allopurinol in rats. (1999)

In this study, the hypouricemic efficacy of a novel xanthine oxidase/xanthine dehydrogenase inhibitor, TEI-6720, was compared with that of allopurinol in a hyperuricemic rat model established by feeding the animals oxonate, a uricase inhibitor. In addition, using normal rats, the changes in xanthine concentration in plasma and the concentrations and absolute quantities of uric acid, allantoin and xanthine in urine were analyzed during a 28-day period of repeated administration of TEI-6720 to determine the changes occurring during this period and the conditions required for the formation of xanthine crystals and calculi in comparison with allopurinol. TEI-6720 and allopurinol caused a significant dose-dependent decrease in plasma uric acid levels in the hyperuricemic rat model and the ED50 of TEI-6720 was lower than that of allopurinol, indicating that in terms of hypouricemic efficacy TEI-6720 is more potent than allopurinol. TEI-6720 also showed more potent activity than allopurinol in decreasing urinary uric acid and allantoin levels in normal rats. In addition, TEI-6720 and allopurinol showed similar dose-response curves for the decrease in uric acid or allantoin concentration, and the associated increase in xanthine concentration, indicating that TEI-6720 and allopurinol have similar pharmacological characteristics although the dosage required differs. The efficacy of TEI-6720 in increasing plasma and urinary xanthine levels in normal rats was approximately 10- to 30-fold greater than that of allopurinol. However, with respect to renal xanthine calculus formation, there was only about a 3-fold difference in dosage comparing TEI-6720 and allopurinol. This difference suggests that there may be another factor independent of xanthine, and dependent on the drug itself, involved in renal calculus formation caused by allopurinol. The daily excretion of purine metabolites per body weight was about 20-fold higher in rats than in humans. From these results, it is concluded that TEI-6720 has potent hypouricemic activity and that, compared to allopurinol, administration of TEI-6720 is not likely to result in a higher incidence of calculus formation.
[Advances in the study of regulation of novel organic cation transporter-2]. (2009)

Novel organic cation transporter-2 (OCTN2), a member of the organic cation transporter family, may transport carnitine and multiple organic cationic drugs. Thus OCTN2 possesses substantial roles in physiology and pharmacology. A number of researches have proven that many factors can regulate the expression and/or function of OCTN2 via different pathways, and then may affect the homeostasis and disposition of drugs. This paper reviews recent progresses in this field.
DYNAMICAL SYSTEM ANALYSIS OF STAPHYLOCOCCUS EPIDERMIDIS BLOODSTREAM INFECTION (2008)

Unlike many localized infections, the development and resolution of bacteremia involves physical and immunological interactions between many anatomic sites. In an effort to better understand these interactions, we developed a computational model of bacteremia as a dynamical system fashioned after multicompartmental pharmacodynamic models, incorporating bacterial proliferation and clearance in the blood, liver, spleen, and lungs, and the transport of pathogens between these sites. A system of four first-order homogeneous ODEs was developed. Blood and organ bacterial burdens were measured at various time points from 3 to 48 h postinoculation using an LD25 murine model of Staphylococcus epidermidis bacteremia. Using these empiric data, solutions to the mathematical model were recovered. A bootstrap resampling method was used to generate 95% confidence intervals around the solved parameters. The validity of the model was examined in parallel experiments using animals acutely immunocompromised with cyclophosphamide; the model captured abnormalities in bacterial partitioning previously described with this antineoplastic agent. Lastly, the approach was used to explore possible benefits to clinically observed hyperdynamic blood flow during sepsis: in simulation, normal mice, but not those treated with cyclophosphamide, enjoyed significantly more rapid bacterial clearance from the bloodstream under hyperdynamic conditions.
Life, death, and lawfulness on the electronic frontier (1997)

Article Free Access Share on Life, death, and lawfulness on the electronic frontier Authors: James Pitkow Xerox Palo Alto Research Center, 3333 Coyote Hill Road, Palo Alto, CA Xerox Palo Alto Research Center, 3333 Coyote Hill Road, Palo Alto, CAView Profile , Peter Pirolli Xerox Palo Alto Research Center, 3333 Coyote Hill Road, Palo Alto, CA Xerox Palo Alto Research Center, 3333 Coyote Hill Road, Palo Alto, CAView Profile Authors Info & Claims CHI '97: Proceedings of the ACM SIGCHI Conference on Human factors in computing systemsMarch 1997 Pages 383–390https://doi.org/10.1145/258549.258805Published:27 March 1997Publication History 84citation481DownloadsMetricsTotal Citations84Total Downloads481Last 12 Months22Last 6 weeks2 Get Citation AlertsNew Citation Alert added!This alert has been successfully added and will be sent to:You will be notified whenever a record that you have chosen has been cited.To manage your alert preferences, click on the button below.Manage my Alerts New Citation Alert!Please log in to your account Save to BinderSave to BinderCreate a New BinderNameCancelCreateExport CitationPublisher SiteeReaderPDF