gebhart/patrepeval huggingface dataset:
Structural Characterization of Natural and Recombinant Human Granulocyte Colony-Stimulating Factors1 (1990)

Granulocyte colony-stimulating factor (G-CSF) is a glycoprotein which stimulates predominantly neutrophilic granulocyte colony formation in mammals. Natural human G-CSF (hG-CSF) and recombinant hG-CSF produced in Chinese hamster ovary (CHO) cells transfected with the cDNA clone for hG-CSF have been purified to apparent homogeneity for structural and biological comparison. The amino acid sequence of recombinant hG-CSF, composed of 174 amino acid residues, was identical with that of natural hG-CSF and also with the sequence predicted from the cDNA. Both forms of hG-CSF have a free Cys-17 and two intramolecular disulfide linkages, between Cys-36 and Cys-42, and between Cys-64 and Cys-74. The O-glycosylation occurred at Thr-133 in both hG-CSFs. Similar CD spectra were obtained for both hG-CSFs. Additionally, both forms showed almost the same biological activities determined by in vitro colony-forming assay and in vivo assay. It is thus concluded that the recombinant hG-CSF is indistinguishable from its natural counterpart and that the former is valuable for more detailed characterization and clinical use.
311C90, A new central and peripherally acting 5-HT 1D receptor agonist in the acute oral treatment of migraine (1996)

311C90 is a novel, centrally and peripherally, acting 5-hydroxytryptamine1D receptor agonist. We investigated the efficacy and safety of 1, 5, and 25 mg of oral 311C90 in the acute treatment of migraine in a randomized, double-blind, placebo-controlled, parallel-group clinical trial involving 84 patients. The proportion of patients in whom the headache improved within 2 hours from moderate or severe to mild or no pain (primary efficacy measure) was 15% for placebo-treated patients and 27% (1 mg), 62% (5 mg), and 81% (25 mg) for patients treated with 311C90. Treatment differences compared with placebo were 12% (95% CI - 12, 37; p = 0.460) for 1 mg 311C90, 47% (CI 21, 73; p < 0.005) for 5 mg 311C90, and 66% (CI 43,89; p < 0.001) for 25 mg 311C90. Photophobia and nausea also showed improvement after 311C90. Adverse events were generally mild and transient in all treatment groups. There were no clinically significant changes in ECG recordings, blood pressure, or laboratory tests. Oral 311C90 (5 and 25 mg) is highly effective and well tolerated in the acute treatment of migraine. The response rates and treatment differences compared with placebo in this study suggest possible superiority over existing antimigraine therapies. This needs to be confirmed in formal comparative trials.
Pharmacokinetics and pharmacodynamics of single and multiple doses of the glucagon receptor antagonist LGD‐6972 in healthy subjects and subjects with type 2 diabetes mellitus (2016)

Inhibition of glucagon action by LGD-6972 was associated with decreases in glucose in both healthy and T2DM subjects, the magnitude of which was sufficient to predict improvement in glycaemic control with longer treatment duration in T2DM patients. The safety and pharmacological profile of LGD-6972 after 14 days of dosing supports continued clinical development.
Minireview: Development and Differentiation of Gut Endocrine Cells (2004)

For over 30 yr, it has been known that enteroendocrine cells derive from common precursor cells in the intestinal crypts. Until recently, relatively little was understood about the events that result in commitment to endocrine differentiation or the segregation of over 10 different hormone-expressing cell types in the gastrointestinal tract. The earliest cell fate decisions appear to be regulated by the Notch signaling pathway. Notch is inactive in endocrine precursor cells, allowing for expression of the proendocrine basic helix-loop-helix proteins Math1 and neurogenin3. Differentiating precursor cells activate Notch in neighboring cells to switch off expression of proendocrine factors and inhibit endocrine differentiation. Math1 is the first factor involved in endocrine specification, committing cells to become one of three secretory lineages-goblet, Paneth, and enteroendocrine. Neurogenin3 appears to be a downstream target that is essential for endocrine cell differentiation. Events that control the segregation of each mature lineage from progenitor cells have not been characterized in detail. The transcription factors Pax4, Pax6, BETA2/NeuroD, and pancreatic-duodenal homeobox 1 have all been implicated in enteroendocrine differentiation. BETA2/NeuroD appears to coordinate secretin gene expression in S-type enteroendocrine cells with cell cycle arrest as cells terminally differentiate. Powerful genetic approaches have established the murine intestine as the most important model for studying enteroendocrine differentiation. Enteroendocrine cells in the mouse are remarkably similar to those in humans, making it likely that insights learned from the mouse may contribute to both our understanding and treatment of a variety of human disorders.
Novel Cyclopropylindole Conjugates and Dimers: Synthesis and Anti-Cancer Evaluation (2001)

There is a considerable interest currently in the development of DNA sequence specific or selective agents for genetic targeting for the control of gene expression, for application in diagnosis or ultimately in therapy. In this context CC-1065 is one of the most impressive lead compounds isolated in trace quantities from the culture of Streptomyces zelensis at Upjohn in 1978. The unique structure was confirmed by single X-ray in 1981. However CC-1065 cannot be used in humans because it was found that it caused delayed deaths in experimental animals. In the search for compounds with better antitumor selectivity and DNA sequence specificity many CC-1065 analogs have been synthesized in an attempt to avoid the undesired side effects while retaining its potency against tumor cells. Two successful attempts in the modification in the active moiety of the parent natural product 1,2,8,8a-tetrahydro-7-methylcyclopropa[3,2-e]indole-4-one (CPI) and 1,2,9,9a-tetrahydrocyclopropa[c]benz[e]indole-4-one (CBI) have been made. We review here recent progress with the analogs of CPI and CBI and their conjugates both by solution and solid phase, also the progress and development of CPI and CBI conjugates with polyamides (information reading molecules in the minor groove of DNA). Since CPI-CPI dimers are significantly more potent than CC-1065 in vitro and in vivo, a large number of CBI-CBI dimers with varying linkers lengths and positions synthesized in our group and their pharmacological properties have been reviewed.
Approved and Future Pharmacotherapy for Multiple Sclerosis (2002)

Although treatment with interferon beta, glatiramer acetate, and mitoxantrone, the approved therapies, provide important treatment options for patients with relapsing-remitting MS and secondary progressive MS, the potential benefits of other medications, including statins, should be explored in controlled clinical trials.
Cell Localization and Regulation of Expression of Cytochrome P450 1A1 and 2B1 in Rat Lung After Induction With 3-Methylcholanthrene using mRNA Hybridization and Immunohistochemistry (1994)

In order to characterize the response of various pulmonary cell types to polycyclic aromatic hydrocarbons, the expression of cytochrome P450 (CYP) 1A1 and 2B1 mRNA in the lung of rats, with or without induction by 3-methylcholanthrene (3MC), was analyzed by in situ hybridization using appropriate 35S-labeled riboprobes. The expression of the corresponding proteins was investigated immunohistochemically. Following induction with 3MC, the kinetics of mRNA expression differed considerably between Clara cells and type II pneumocytes and venous endothelial cells. In Clara cells, mRNA expression was detected as early as 1 h after induction, peaked between 2 and 4 h, and was completely undetectable at 14 h. In contrast, venous endothelial cells and type II pneumocytes exhibited permanent mRNA expression of CYP 1A1 in 3MC-pretreated rats. These kinetic results explain the striking absence of correlation between mRNA and protein expression observed in Clara cells 24 h after the end of the induction protocol, as these cells exhibited intense protein expression with no mRNA. In contrast, a good correlation was observed for mRNA and protein expression of CYP 2B1, with similar expressions for Clara cells and type II pneumocytes, but no expression in endothelial cells. This study clearly distinguished the regulation of CYP 1A1 expression in the rat lung from that described in the liver. The differences observed in the various lung cell types, whatever the post-transcriptional mechanisms involved, emphasize that studies must be performed at the cellular level in order to understand the specific response to xenobiotics, not only of this organ as a whole but also of its various anatomic structures.
Generation of diverse high-affinity human monoclonal antibodies by repertoire cloning. (1991)

Combinatorial libraries of antibody heavy and light chains derived from the peripheral blood lymphocytes of an individual immunized with tetanus toxoid have been expressed in Escherichia coli by using phage lambda vectors. Screening of the libraries allowed identification of a large number of human monoclonal Fab fragments specific for tetanus toxoid. Initial studies suggested considerable sequence diversity in these antibodies. The method should allow the generation of many human monoclonal antibodies of interest and the dissection of human humoral immune responses.
Isolation of a cDNA encoding a human serum marker for acute pancreatitis. Identification of pancreas-specific protein as pancreatic procarboxypeptidase B. (1992)

A human pancreas-specific protein (PASP), previously characterized as a serum marker for acute pancreatitis and pancreatic graft rejection, has been identified as pancreatic procarboxypeptidase B (PCPB). cDNAs encoding PASP/PCPB were isolated from a human pancreas cDNA library using a combination of nucleic acid hybridization screening and immunoscreening with antisera raised against native PASP. The deduced amino acid sequence of PASP/PCPB cDNA predicts the translation of a 416-amino acid preproenzyme with a 15-amino acid signal/leader peptide and a 95-amino acid activation peptide. The proenzyme portion of this protein has 76% identity with rat PCPB and 84% identity with bovine carboxypeptidase B. DNA and RNA blot analyses indicate that human PCPB mRNA (1,400 nucleotides) is transcribed from a single locus in the human genome in a tissue-specific fashion. N-terminal sequencing of native PASP and the specific immunoreactivity of bacterially expressed PASP/PCPB with native PASP antibodies confirm the identification of PASP as human pancreatic PCPB.
Strain-Dependent Differences in Susceptibility of Mice to Experimental Candidosis (1986)

Journal Article Strain-Dependent Differences in Susceptibility of Mice to Experimental Candidosis Gabriel Marquis, Gabriel Marquis Departments of Microbiology and Immunology and of Pathology, Université de Montréal, Montreal, Quebec, Canada Search for other works by this author on: Oxford Academic PubMed Google Scholar Serge Montplaisir, Serge Montplaisir Departments of Microbiology and Immunology and of Pathology, Université de Montréal, Montreal, Quebec, Canada Please address requests for reprints to Dr. Serge Montplaisir, Department of Microbiology and Immunology, Université de Montréal, P. O. Box 6128, Station A, Montreal, Canada H3C 317. Search for other works by this author on: Oxford Academic PubMed Google Scholar Micheline Pelletier, Micheline Pelletier Departments of Microbiology and Immunology and of Pathology, Université de Montréal, Montreal, Quebec, Canada Search for other works by this author on: Oxford Academic PubMed Google Scholar Serge Mousseau, Serge Mousseau Departments of Microbiology and Immunology and of Pathology, Université de Montréal, Montreal, Quebec, Canada Search for other works by this author on: Oxford Academic PubMed Google Scholar Pierre Auger Pierre Auger Departments of Microbiology and Immunology and of Pathology, Université de Montréal, Montreal, Quebec, Canada Search for other works by this author on: Oxford Academic PubMed Google Scholar The Journal of Infectious Diseases, Volume 154, Issue 5, November 1986, Pages 906–909, https://doi.org/10.1093/infdis/154.5.906 Published: 01 November 1986 Article history Received: 24 January 1986 Revision received: 03 June 1986 Published: 01 November 1986
Ursolic Acid Simultaneously Targets Multiple Signaling Pathways to Suppress Proliferation and Induce Apoptosis in Colon Cancer Cells (2013)

Ursolic acid (UA), a natural pentacyclic triterpenoid carboxylic acid distributed in medical herbs, exerts antitumor effects and is emerging as a promising compound for cancer prevention and therapy, but its excise mechanisms of action in colon cancer cells remains largely unknown. Here, we identified the molecular mechanisms by which UA inhibited cell proliferation and induced apoptosis in human colon cancer SW480 and LoVo cells. Treatment with UA led to significant inhibitions in cell viability and clone formation and changes in cell morphology and spreading. UA also suppressed colon cancer cell migration by inhibiting MMP9 and upregulating CDH1 expression. Further studies showed that UA inhibited the phosphorylation of Akt and ERK proteins. Pretreatment with an Akt or ERK-specific inhibitor considerably abrogated the proliferation inhibition by UA. UA also significantly inhibited colon cancer cell COX-2 expression and PGE2 production. Pretreatment with a COX-2 inhibitor (celecoxib) abrogated the UA-induced cell proliferation. Moreover, we found that UA effectively promoted NF-κB and p300 translocation from cell nuclei to cytoplasm, and attenuated the p300-mediated acetylation of NF-κB and CREB2. Pretreatment with a p300 inhibitor (roscovitine) abrogated the UA-induced cell proliferation, which is reversed by p300 overexpression. Furthermore, UA treatment induced colon cancer cell apoptosis, increased the cleavage of PARP, caspase-3 and 9, and trigged the release of cytochrome c from mitochondrial inter-membrane space into cytosol. These results indicate that UA inhibits cell proliferation and induces apoptosis in colon cancer cells through simultaneous modulation of the multiple signaling pathways such as MMP9/CDH1, Akt/ERK, COX-2/PGE2, p300/NF-κB/CREB2, and cytochrome c/caspase pathways.
Adipose Tissue-Derived Multipotent Stromal Cells Have a Higher Immunomodulatory Capacity Than Their Bone Marrow-Derived Counterparts (2013)

Adipose tissue-derived multipotent stromal cells (AT-MSCs) are studied as an alternative to bone marrow-derived multipotent stromal cells (BM-MSCs) for immunomodulatory treatment. In this study, we systematically compared the immunomodulatory capacities of BM-MSCs and AT-MSCs derived from age-matched donors. We found that BM-MSCs and AT-MSCs share a similar immunophenotype and capacity for in vitro multilineage differentiation. BM-MSCs and AT-MSCs showed comparable immunomodulatory effects as they were both able to suppress proliferation of stimulated peripheral blood mononuclear cells and to inhibit differentiation of monocyte-derived immature dendritic cells. However, at equal cell numbers, the AT-MSCs showed more potent immunomodulatory effects in both assays as compared with BM-MSCs. Moreover, AT-MSCs showed a higher level of secretion of cytokines that have been implicated in the immunomodulatory modes of action of multipotent stromal cells, such as interleukin-6 and transforming growth factor-β1. This is correlated with higher metabolic activity of AT-MSCs compared with BM-MSCs. We conclude that the immunomodulatory capacities of BM-MSCs and AT-MSCs are similar, but that differences in cytokine secretion cause AT-MSCs to have more potent immunomodulatory effects than BM-MSCs. Therefore, lower numbers of AT-MSCs evoke the same level of immunomodulation. These data indicate that AT-MSCs can be considered as a good alternative to BM-MSCs for immunomodulatory therapy.
Activated CD4+ CD25+ T cells suppress antigen‐specific CD4+ and CD8+ T cells but induce a suppressive phenotype only in CD4+ T cells (2005)

CD4(+) CD25(+) regulatory T cells are increasingly recognized as central players in the regulation of immune responses. In vitro studies have mostly employed allogeneic or polyclonal responses to monitor suppression. Little is known about the ability of CD4(+) CD25(+) regulatory T cells to suppress antigen-specific immune responses in humans. It has been previously shown that CD4(+) CD25(+) regulatory T cells anergize CD4(+) T cells and turn them into suppressor T cells. In the present study we demonstrate for the first time in humans that CD4(+) CD25(+) T cells are able to inhibit the proliferation and cytokine production of antigen specific CD4(+) and CD8(+) T cells. This suppression only occurs when CD4(+) CD25(+) T cells are preactivated. Furthermore, we could demonstrate that CD4(+) T-cell clones stop secreting interferon-gamma (IFN-gamma), start to produce interleukin-10 and transforming growth factor-beta after coculture with preactivated CD4(+) CD25(+) T cells and become suppressive themselves. Surprisingly preactivated CD4(+) CD25(+) T cells affect CD8(+) T cells differently, leading to reduced proliferation and reduced production of IFN-gamma. This effect is sustained and cannot be reverted by exogenous interleukin-2. Yet CD8(+) T cells, unlike CD4(+) T cells do not start to produce immunoregulatory cytokines and do not become suppressive after coculture with CD4(+) CD25(+) T cells.
Metalloproteases Cleave the Urokinase-Type Plasminogen Activator Receptor in the D1-D2 Linker Region and Expose Epitopes not Present in the intact Soluble Receptor (2002)

Proteolytic cleavage of the urokinase plasminogen activator receptor (uPA(R)) prevents the binding of uPA and vitronectin while generating biologically active uPAR fragments. We have recently shown that matrix metalloproteinase-12 (MMP-12) releases cellular uPAR-antigen from stimulated human micro-vascular endothelial cells providing a novel feedback mechanism between the plasminogen activation and MMP systems. We now show that MMP-12 and other MMPs directly and efficiently cleave uPAR at the Thr86 paralal Tyr87 peptide bond located in the linker region connecting uPAR domains 1 and 2, releasing the major ligand binding domain 1 from the rest of the receptor. The possible biological importance of uPAR cleavage by MMPs is supported by the observation that also murine uPAR is cleaved by MMP-12 (at the Pro89 paralal Gln90 peptide bond), despite the limited sequence homology between the linker regions. Using an antibody raised against the human uPAR linker region we show that this region of uPAR, which contains the chemotactic SRSRY epitope, is exposed upon MMP cleavage.
Pre-Existing Immunity to Tyrosinase-Related Protein (TRP)-2, a New TRP-2 Isoform, and the NY-ESO-1 Melanoma Antigen in a Patient with a Dramatic Response to Immunotherapy (2002)

We have performed a detailed analysis of the recognition of melanoma Ags by the tumor-infiltrating lymphocytes (TIL) 1790, isolated from a patient who experienced a dramatic tumor regression following immunization with peptides from the gp100, MART-1, and tyrosinase Ags. This TIL was found to recognize HLA-A2-restricted CTL epitopes in tyrosinase-related protein (TRP)-2 (clone MR7) and NY-ESO-1 (clone M8). These epitopes were the same as the previously identified nonapeptide TRP-2: 180-188, and the overlapping NY-ESO-1 peptides, obtained by using lymphocytes from in vitro stimulation. We also cloned a previously unknown TRP-2 mRNA isoform (TRP-2-6b) that contained two novel exons alternatively spliced from the sixth intron between exons 6 and 7 of TRP-2 mRNA. The isoform encoded an HLA-A2-restricted antigenic epitope recognized by TIL clone MB4. An immunologic analysis of the patient's PBMC obtained before treatment showed the presence of high reactivity against NY-ESO-1 and both TRP-2 Ags, but not the Ags used for immunization. Because immune response against these Ags was less pronounced, it is possible that NY-ESO-1, TRP-2, and TRP-2-6b may be of importance in the generation of CTL-mediated tumor destruction and may have played a role in the dramatic tumor regression seen in this patient.
repp86: A human protein associated in the progression of mitosis. (2003)

Human repp86 becomes detectable in the nucleoplasm of cycling cells at the G(1)-S boundary, condenses at the centrosomes with the onset of mitosis, during which it progressively locates to the mitotic spindle and to the midbody, and vanishes at the completion of cytokinesis. The repp86 cDNA was cloned and sequenced. Full-length repp86 and its COOH-terminal domain cosediment with polymerized microtubules, linking repp86 to the family of microtubule-associated proteins. During prophase and metaphase, repp86 interacts on the mitotic spindle with the putative motor protein Hklp2. Thus, repp86 may function in targeting Hklp2 to the microtubule minus ends, its activity being regulated by phosphorylation of serine/threonine residues. Exogenous overexpression of repp86 provokes accumulation of cells in G(2)-M phase and subsequent polyploidization, suggesting that excess repp86 may interfere with correct nuclear division.
Comparative analysis of pregnancy rates after the transfer of early dividing embryos versus slower dividing embryos (2004)

Early division is associated with embryo quality and a very easy and successful embryo transfer selection method. Our results also suggest that when EDE are available, both tubal and uterine embryo transfer can be considered. When only LDE are available, however, tubal transfer should be the preferred transfer route.
Infant mortality statistics from the 2004 period linked birth/infant death data set. (2007)

The U.S. infant mortality rate was 6.78 infant deaths per 1000 live births in 2004 compared with 6.84 in 2003. Infant mortality rates ranged from 4.67 per 1,000 live births for Asian and Pacific Islander mothers to 13.60 for non-Hispanic black mothers. Among Hispanics, rates ranged from 4.55 for Cuban mothers to 7.82 for Puerto Rican mothers. Infant mortality rates were higher for those infants whose mothers were born in the 50 states and the District of Columbia, were unmarried, or were born in multiple births. Infant mortality was also higher for male infants and infants born preterm or at low birthweight. The neonatal mortality rate declined from 4.63 in 2003 to 4.52 in 2004 while the postneonatal mortality rate was essentially unchanged. Infants born at the lowest gestational ages and birthweights have a large impact on overall U.S. infant mortality. More than one-half (55 percent) of all infant deaths in the United States in 2004 occurred to the 2 percent of infants born at less than 32 weeks of gestation. Still, infant mortality rates for late preterm (34-36 weeks of gestation) infants were three times those for term (37-41 week) infants. The three leading causes of infant death-Congenital malformations, low birthweight, and SIDS-taken together accounted for 45 percent all infant deaths. Results from a new analysis of preterm-related causes of death show that 36.5 percent of infant deaths in 2004 were due to preterm-related causes. The preterm-related infant mortality rate for non-Hispanic black mothers was 3.5 times higher, and the rate for Puerto Rican mothers was 75 percent higher than for non-Hispanic white mothers.