gebhart/patrepeval huggingface dataset:
The interferons. Mechanisms of action and clinical applications (1991)

The interferons (IFN) are one of the body's natural defensive responses to such foreign components as microbes, tumors, and antigens. The IFN response begins with the production of the IFN proteins (alpha, beta, and gamma), which then induce the antiviral, antimicrobial, antitumor, and immunomodulatory actions of IFN. Recent advances have led to Food and Drug Administration approval of five clinical indications for IFN. Interferon alfa is approved for hairy-cell leukemia, condyloma acuminatum, Kaposi's sarcoma in the acquired immunodeficiency syndrome, and non-A, non-B (type C) viral hepatitis. Interferon gamma has properties distinctive from those of IFNs alpha and beta and is approved as an immunomodulatory treatment for chronic granulomatous disease. Promising clinical results with IFNs have also been reported for basal cell carcinoma, chronic myelogenous leukemia, cutaneous squamous cell carcinoma, early human immunodeficiency virus infection, hepatitis B, and laryngeal papillomatosis. Future clinical uses of IFNs may emphasize combination therapy with other cytokines, chemotherapy, radiation, surgery, hyperthermia, or hormones.
[In vitro activities of newly developed quinolones, fleroxacin, lomefloxacin and sparfloxacin against Mycobacterium tuberculosis]. (1991)

In vitro antituberculous activities of three newly developed quinolones, fleroxacin (FLRX, AM-833), lomefloxacin (LFLX) and sparfloxacin (SPFX, AT-4140) were evaluated in comparison to that of ofloxacin (OFLX) using M. tuberculosis strains isolated from patients and the Ogawa egg medium. SPFX was apparently more active than OFLX, but both FLRX and LFLX were less active. SPFX inhibited completely the growth of all 20 strains of M. tuberculosis isolated from patients who were not previously treated with OFLX in a concentration of 1.25 micrograms/ml. However, this agent inhibited the growth of only 4 strains (28.6%) of 14 OFLX-resistant M. tuberculosis in a concentration of 1.25 micrograms/ml, suggesting a partial cross-resistance between SPFX and OFLX.
Histopathological and immunohistological analyses in IgA deficient lymphoplasia (aly/aly) mouse. (2001)

The aly/aly mouse has a severe immunodeficiency, because it lacks peripheral lymph nodes as well as IgA and IgG immunoglobulin synthesis. In the present study, we performed histopathological and immunohistological examinations to clarify histological disorders of various immune organs in these mice. Carbon CH40 injections into the apex of the tongue confirmed the absence of submandibular lymph nodes in aly/aly mice. The thymus had a poorly constructed cortex and medulla, and the number of lymphoid follicles was clearly decreased in the spleen. No IgG- or IgA- producing cells were found in any immune organs, including the mucosal immune sites, though several IgM -producing cells were identified. Other characteristic findings included perivascular lymphocytes accumulation in the salivary glands, lungs, liver and pancreas, which caused tissues damage. These results demonstrated that the various lymphoid tissues disorders and organ-specific lymphocyte infiltration cause immuno-deficiency in the aly/aly mouse.
Structural Insights into the Interaction of ROCKI with the Switch Regions of RhoA (2004)

The Rho-ROCK pathway modulates the phosphorylation level of a variety of important signaling proteins and is thereby involved in miscellaneous cellular processes including cell migration, neurite outgrowth, and smooth muscle contraction. The observation of the involvement of the Rho-ROCK pathway in tumor invasion and in diseases such as hypertension and bronchial asthma makes it an interesting target for drug development. We herein present the crystal structure of the complex between active RhoA and the Rho-binding domain of ROCKI. The Rho-binding domain structure forms a parallel alpha-helical coiled-coil dimer and, in contrast to the published Rho-protein kinase N structure, binds exclusively to the switch I and II regions of the guanosine 5'-(beta,gamma-imido)triphosphate-bound RhoA. The switch regions of two different RhoA molecules form a predominantly hydrophobic patch, which is complementarily bound by two identical short helices of 13 residues (amino acids 998-1010). The identified ROCK-binding site of RhoA strikingly supports the assumption of a common consensus-binding site for effector recognition.
Chemiluminescence : principles and applications in biology and medicine (1988)

A Natural History of Chemiluminescence Detection and Quantification of Chemiluminescence Bioluminescence How Chemical Reactions Produce Light Chemiluminescence Energy Transfer Ultraweak Chemiluminescence Biomedical Applications of Chemiluminescence Synthesis and Perspectives.
The role of calcium, pH, and cell proliferation in the programmed (apoptotic) death of androgen-independent prostatic cancer cells induced by thapsigargin. (1994)

Calcium (Ca2+) accumulates within the endoplasmic reticulum of cells through function of the sarcoplasmic reticulum and endoplasmic reticulum Ca(2+)-dependent ATPase family of intracellular Ca(2+)-pumping ATPases. The resulting pools have important signaling functions. Thapsigargin (TG) is a sesquiterpene gamma-lactone which selectively inhibits the sarcoplasmic reticulum and endoplasmic reticulum Ca(2+)-dependent ATPase pumps with a 50% inhibitory concentration of approximately 30 nM. Treatment of androgen-independent prostate cancer cells of both rat and human origin with TG inhibits their endoplasmic reticulum Ca(2+)-dependent ATPase activity, resulting in a 3-4-fold elevation in the level of intracellular free Ca2+ (Cai) within minutes of exposure. Due to a secondary influx of extracellular Ca2+, this increase in Cai is sustained, resulting in morphological (cell rounding) and biochemical changes within 6-12 h (enhanced calmodulin, glucose regulated protein, and tissue transglutaminase expression, and decreased expression of the G1 cyclins). Within 24 h of exposure, androgen-independent prostatic cancer cells stop progression through the cell cycle, arrest out of cycle in G0, and irreversibly lose their ability to proliferate with a median effective concentration value of 31 nM TG. During the next 24-48 h, the genomic DNA of the G0-arrested cells undergoes double-strand fragmentation. This is followed by the loss of plasma membrane integrity and fragmentation of the cell into apoptotic bodies. During this process, there is no acidification in the intracellular pH. Using cells transfected with the avian M(r) 28,000 calbindin D Ca(2+)-buffering protein, it was demonstrated that the programmed death initiated by TG is critically dependent upon an adequate (i.e., 3-4-fold) sustained (> 1 h) elevation in Cai and not depletion of the endoplasmic reticulum pools of Ca2+. These results demonstrate that TG induces programmed cell death in androgen-independent prostatic cancer cells in a dose-dependent manner and that this death does not require proliferation or intracellular acidification but is critically dependent upon an adequate, sustained (i.e., > 1 h) elevation in Cai.
A low band gap, solution processable oligothiophene with a dialkylated diketopyrrolopyrrole chromophore for use in bulk heterojunction solar cells (2009)

Bulk heterojunction solar cells are fabricated from blends of oligothiophene with a dialkylated diketopyrrolopyrrole chromophore:[6,6]-phenyl C71 butyric acid methyl ester. Absorption and photocurrent of the films extend to 800 nm. A power conversion efficiency (PCE) of 3.0% is obtained under simulated 100 mW/cm2 AM1.5 illumination with a 9.2 mA/cm2 short-circuit current density and an open-circuit voltage of 0.75 V. The hole and electron mobilities in the 50:50 blend are fairly balanced, 1.0×10−4 and 4.8×10−4 cm2/V s, respectively. This is the highest PCE reported to date for solar cells using solution processable small molecules.
Confusing signals: Recent progress in CTLA-4 biology (2015)

The mechanism of action of cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) remains surprisingly unclear. Regulatory T (Treg) cells can use CTLA-4 to elicit suppression; however, CTLA-4 also operates in conventional T cells, reputedly by triggering inhibitory signals. Recently, interactions mediated via the CTLA-4 cytoplasmic domain have been shown to preferentially affect Treg cells, yet other evidence suggests that the extracellular domain of CTLA-4 is sufficient to elicit suppression. Here, we discuss these paradoxical findings in the context of CTLA-4-mediated ligand regulation. We propose that the function of CTLA-4 cytoplasmic domain is not to transmit inhibitory signals but to precisely control the turnover, cellular location, and membrane delivery of CTLA-4 to facilitate its central function: regulating the access of CD28 to their shared ligands.
Advancements in the Treatment of Psoriasis: Role of Biologic Agents (2004)

Biologic agents appear to offer a safe and effective alternative to conventional systemic therapies and phototherapy for the treatment of moderate-to-severe chronic plaque psoriasis. The biologics appear to be safer than traditional therapies, although long-term safety data still need to be established.
Homoisochroman‐Derivate mit basischer Seitenkette in 1‐Stellung 2. Mitt. über Untersuchungen in der Homoisochroman‐Reihe (1973)

Abstract 1‐Cyan‐homoisochromane ( 1 ; R′ = H) lassen sich über ihre Carbanionen in 1‐Stellung mit β‐Dialkylaminoäthylchloriden zu 2 β‐aminoäthylieren und mit α‐halogenierten Aminen zu 3 aminomethylieren. ‐ Durch Einwirkung von Lithiumalanat werden 1 ‐Cyan‐homoisochromane und ihre Alkylierungsprodukte in 1 ‐Stellung ( 1 ; R′ = H oder Alkylrest) zu den entsprechenden 1‐Aminomethyl‐homoisochromanen 4 reduziert, während aus 1‐Acyl‐1‐cyan‐homoisochromanen ( 1i oder 11 ) γ‐Hydroxyamine ( 4k bzw. 4m ) entstehen.
Induction of Osteogenic Differentiation by Hedgehog Proteins (1997)

In this study we asked whether members of the hedgehog gene family are involved in osteogenesis. C3H10T1/2 cells and MC3T3-E1 cells expressed the putative hedgehog receptor patched (Ptc) gene. Medium conditioned by chicken embryo fibroblast cultures expressing either Indian hedgehog or Sonic hedgehog stimulated alkaline phosphatase (APase) activity in cultures of the mouse mesenchymal cell line C3H10T1/2 and the osteoblastic cell line MC3T3-E1. These stimulatory effects were synergistically enhanced by bone morphogenetic protein-2 (BMP-2). Treatment with the amino-terminal portion of recombinant Sonic hedgehog proteins (rShh-N) up-regulated the expression of the Ptc gene within 12 h and increased production of APase in C3H10T1/2. rShh-N and BMP-2 also synergistically stimulated APase activity. rShh-N treatment did not affect the expression levels of Bmp-2, -4, -5, -6 and -7 genes. These findings indicate that hedgehog proteins directly act on osteogenic precursor cells and osteoblasts and stimulate osteogenic differentiation of these cells in co-operation with BMPs.
Liberation from Rectangles: A Tiling Method for Dynamic Modification of Objects on Raster Displays (1988)

When graphics objects (also called segments) are used on raster display hardware, problems arise because of the mismatch between the high level requirements of object manipulation, and the low level representation from which the image is refreshed. This paper describes a tiling algorithm which provides a solution to the problems of damage repair and hit detection. In particular methods for handling object priority are discussed and experimental results showing the performance of the algorithm for a number of cases are presented.
PRIMARY ADHESION OF ENTEROMORPHA (CHLOROPHYTA, ULVALES) PROPAGULES: QUANTITATIVE SETTLEMENT STUDIES AND VIDEO MICROSCOPY1 (1997)

ABSTRACT Quantitative methods and associated kinetic analyses have been used for the first time to study detailed aspects of the settlement and adhesion of various types of Enteromorpha popagule. Time course experiments showed that quadri and biflagellate zoospores and zygotes adhered rapidly, but a proportion within any one population appeared to be incompetent at adhering to the substratum. Kinetic (Scatchard) analysis of adhesion experiments performed at a range of zoospore concentrations revealed density‐dependent effects not previously reported, with positive cooperativity at low spore densities and negative cooperativity at high spore densities. High‐resolution video microscopy was used for the first time to reveal details of the various stages in the settlement and adhesion of zoospores and zygotes. Novel observations were made of an initial, temporary phase of attachment via the apical papilla, followed by a permanent phase of commitment, characterized by discharge of adhesive‐containing cytoplasmic vesicles, as the cell contracted against the surface, and adsorption of flagella. The phase of commitment was followed by exploitation of the surface through amoeboid‐like movements at the interface. Gregarious settlement behavior was frequently observed leading to the formation of rafts of cells. The possible mechanisms and significance of density‐dependent spore adhesion are discussed.
Isomerism of Bis(7-azaindolyl)methane (2002)

Three isomers of bis(7-azaindolyl)methane have been synthesized and fully characterized. Isomers 1 and 2 contain 7-azaindolyl groups that are bound to the CH(2) group through nitrogen atoms. However, 1 contains two "normal" 7-azaindolyl groups, whereas 2 contains both a normal 7-azaindolyl group and a tautomer form of 7-azaindolyl. The third isomer 4 contains two 7-azaindolyl groups that are bound to the CH(2) group through the carbon atom at the position-3. These three isomers show distinct absorption and emission spectra, attributable to the different forms of 7-azaindolyl groups in the isomers, as indicated by the results of ab initio calculations. [structure: see text]
Disorders of Hemostasis (1991)

The third edition encompasses disorders of hemostasis. It begins with a review of the history of the development of knowledge about this subject and with a chapter on the laboratory approach to hemostatic disorders. The rest of the volume is devoted to summaries of specific patient problems, their pathogenesis, diagnosis and therapy.
Cancer targeting by TCR gene-engineered T cells directed against Kita-Kyushu Lung Cancer Antigen-1 (2019)

T cell receptor (TCR) gene-engineered T cells have shown promise in the treatment of melanoma and synovial cell sarcoma, but their application to epithelial cancers has been limited. The identification of novel therapeutic TCRs for the targeting of these tumors is important for the development of new treatments. Here, we describe the preclinical characterization of a TCR directed against Kita-Kyushu Lung Cancer Antigen-1 (KK-LC-1, encoded by CT83), a cancer germline antigen with frequent expression in human epithelial malignancies including gastric cancer, breast cancer, and lung cancer. Gene-engineered T cells expressing the KK-LC-1 TCR (KK-LC-1 TCR-Ts) demonstrated recognition of CT83+ tumor lines in vitro and mediated regression of established CT83+ xenograft tumors in immunodeficient mouse models. Cross-reactivity studies based on experimental determination of the recognition motifs for the target epitope did not demonstrate cross-reactivity against other human proteins. CT83 gene expression studies in 51 non-neural tissues and 24 neural tissues showed expression restricted exclusively to germ cells. CT83 was however expressed by a range of epithelial cancers, with the highest expression noted in gastric cancer. Collectively, these findings support the further investigation and clinical testing of KK-LC-1 TCR-Ts for gastric cancer and possibly other malignancies.
Red blood cells, platelets and polymorphonuclear neutrophils of patients with sickle cell disease exhibit oxidative stress that can be ameliorated by antioxidants (2005)

Sickle cell disease (SCD) is basically a red blood cell (RBC) disorder characterised by sickling and haemolysis, but platelets and polymorphonuclear neutrophils (PMN) are also involved. Oxidative damage may play a role in the pathogenesis of SCD. Using flow cytometry, we measured oxidative-state markers simultaneously in RBC, platelets and PMN obtained from 25 normal donors, nine homozygous (SS) patients and six SS/beta-thalassaemia patients. Reactive oxygen species (ROS) and reduced glutathione (GSH) were measured following staining of blood samples with fluorescence probes and gating on specific subpopulations based on size and granularity. Ten- to 30-fold higher ROS production and 20-50% lower GSH content were found in RBC, platelets and PMN from SCD patients versus those of their normal counterparts. This could in part account for the clinical manifestations, such as haemolysis, a hypercoagulable state, recurrent bacterial infections and vaso-occlusive incidences, in SCD. We further showed that exposure of SCD samples to antioxidants, such as N-acetyl-cysteine, vitamin C and vitamin E, decreased their oxidative stress. These results suggest that antioxidant treatment of patients with SCD could reduce oxidative damage to RBC, PMN and platelets, thereby alleviating symptoms associated with their pathology. The flow cytometry techniques presented herein could assist in monitoring the efficacy of such treatment.
Long-term Results of the Dial Osteotomy in the Treatment of High-grade Acetabular Dysplasia (2005)

Therapeutic study, Level IV (case series--no, or historical control group). See the Guidelines for Authors for a complete description of levels of evidence.
The cysteine-rich domain of human proteins, neuronal chimaerin, protein kinase C and diacylglycerol kinase binds zinc. Evidence for the involvement of a zinc-dependent structure in phorbol ester binding (1991)

Diacylglycerol (DG) and its analogue phorbol 12-myristate 13-acetate (PMA) activate the ubiquitous phospholipid/Ca2(+)-dependent protein kinase, protein kinase C (PKC), and cause it to become tightly associated with membranes. DG is produced transiently as it is rapidly metabolized by DG kinase (DGK) to phosphatidic acid. Phorbol esters such as PMA are not metabolized and induced a prolonged membrane association of PKC. Until recently, PKC was the only known phorbol ester receptor. We have shown that a novel brain-specific cDNA, neuronal chimaerin (NC), expressed in Escherichia coli, binds phorbol ester with high affinity, stereospecificity and a phospholipid requirement [Ahmed, Kozma, Monfries, Hall, Lim, Smith & Lim (1990) Biochem. J. 272, 767-773]. The proteins NC, PKC and DGK possess a cysteine-rich domain with the motif HX11/12CX2CXnCX2CX4HX2CX6/7C (where n varies between 12 and 14). The partial motif, CX2CX13CX2C, is present in a number of transcription factors including the steroid hormone receptors and the yeast protein, GAL4, in which zinc plays a structural role of co-ordinating cysteine residues and is essential for DNA binding (protein-nucleic acid interactions). The cysteine-rich domain of NC and PKC is required for phospholipid-dependent phorbol is required for phospholipid-dependent phorbol ester binding, suggesting an involvement of this domain in protein-lipid interactions. We have expressed recombinant NC, PKC and DGK glutathione S-transferase and TrpE fusion proteins in E. coli to investigate the relationship between the cysteine-rich motif, HX11/12CX2CX10-14CX2CX4HX2CX6/7C, zinc and phorbol ester binding. The cysteine-rich domain of NC, PKC and DGK bound 65Zn2+ but only NC and PKC bound [3H]phorbol 12,13-dibutyrate. When NC and PKC were subjected to treatments known to remove metal ions from GAL4 and the human glucocorticoid receptor, phorbol ester binding was inhibited. These data provide evidence for the role of a zinc-dependent structure in phorbol ester binding.
Structure of the N- and O-glycans of the A-chain of human plasma .alpha.2HS-glycoprotein as deduced from the chemical compositions of the derivatives prepared by stepwise degradation with exoglycosidases (1992)

The structure of the glycans of the A-chain of human plasma alpha 2HS-glycoprotein was established from the chemical compositions of its derivatives prepared by sequential enzymatic degradation of the carbohydrate moiety, from the determination of the kind and amount of the monosaccharides liberated after each step of the enzymatic digestion, and from the distinct specificity of the highly purified exoglycosidases. The exoglycosidases were three sialidases (Vibrio cholerae, fowl plague virus, and Arthrobacter ureafaciens), two beta-galactosidases (Streptococcus pneumoniae and bovine testis), one alpha-N-acetylgalactosaminidase, one beta-N-acetylglucosaminidase, and one alpha-mannosidase. Utilizing sialidases with different cleavage specificities, the number of alpha 2-3- and alpha 2-6-linked sialic acid residues could be separately determined. As to the beta-galactosidases, the enzyme isolated from S. pneumoniae cleaves only beta 1-4-linked galactose residues, whereas the bovine testes enzyme acts on both the beta 1-4- and beta 1-3-linked galactose residues. Jack bean beta-N-acetylglucosaminidase cleaves beta 1-2, beta 1-4, and beta 1-6 GlcNAc with higher activity for the beta 1-2. Jack bean alpha-mannosidase cleaves alpha 1-2, alpha 1-6, and alpha 1-3 Man with greater activity for alpha 1-2 and alpha 1-6. Bovine liver alpha-N-acetylgalactosaminidase cleaves O-linked GalNAc. On the basis of these results, the A-chain of alpha 2 HS-glycoprotein was found to possess two biantennary N-glycans and two O-linked trisaccharides.
Cyclin-dependent kinase inhibitor p27KIP1 in lymphoid tissue: p27KIP1 expression is inversely proportional to the proliferative index. (1997)

Cell cycle progression is regulated by the combined action of cyclins, cyclin-dependent kinases (CDKs), and CDK inhibitors (CDKIs). p27KIP1, which has a high degree of similarity with p21WAF1, is a general CDKI thought to be involved in G1 arrest in response to agents that inhibit cell cycle progression. The aims of this study were 1) to establish the pattern of expression of p27KIP1 protein in nontumor lymphoid tissue, 2) to determine whether p27KIP1 is involved in lymphomagenesis, and 3) to address the possible relationship between p27KIP1 and p21WAF1 expression in reactive and tumor lymphoid tissue. p27KIP1 protein was found to be mainly present in quiescent lymphocytes in reactive lymphoid tissue as well as in peripheral blood lymphocytes, with an inverse expression for p27KIP1 and Ki-67 proteins. The same p27KIP1 expression pattern was observed in lymphomas, independently of histological type; small resting cells were p27KIP1 positive, and large proliferating cells were p27KIP1 negative. Therefore, tumors with a low proliferative index were mostly positive, whereas tumors characterized by a higher growth fraction bad low p27KIP1 protein levels. An unexpected finding was the existence of a group of six cases of high-grade lymphomas (three diffuse large B-cell lymphomas and three Burkitt's lymphomas) with homogeneously strong staining for p27KIP1 protein. All 6 of these cases belong to a group of 28 cases characterized by blockage of the p53 tumor suppressor pathway, as determined by genetic (p53 mutation) or immunophenotypic studies (p53+/p21-). p27KIP1 expression was not seen in any case of aggressive non-Hodgkin's lymphoma with an intact p53 pathway. The results indicate that p27KIP1 is down-regulated in lymphomas with a high proliferative index, although it is highly expressed in high-grade lymphomas with defects in the p53 pathway.