gebhart/patrepeval huggingface dataset:
Induction of apoptosis in cultured hepatocytes and in regressing liver by transforming growth factor beta 1. (1992)

In previous studies hepatocytes undergoing cell death by apoptosis but not normal hepatocytes in rat liver showed immunostaining for transforming growth factor beta 1 (TGF-beta 1). Staining was much stronger with antibodies recognizing the pro-region of TGF-beta 1 than the mature peptide itself. Therefore we investigated the ability of both forms of TGF-beta 1 to induce apoptosis in primary cultures of rat hepatocytes. Mature TGF-beta 1 induced rounding up of the cells and fragmentation into multiple vesicles. As revealed by the DNA-specific stain H33258, the chromatin of these cells condensed and segregated into masses at the nuclear membrane; this was obviously followed by fragmentation of the nucleus. Ultrastructurally the cytoplasm was well preserved, as demonstrated by the presence of intact cell organelles. These features strongly suggest the occurrence of apoptosis. Quantification of nuclei with condensed chromatin revealed that mature TGF-beta 1 was 30-fold more effective than the TGF-beta 1 latency-associated protein complex. Finally, we administered TGF-beta 1 in vivo using an experimental model in which regression of rat liver was initiated by a short preceding treatment with the hepatomitogen cyproterone acetate. Two doses of TGF-beta 1, each 1 nM/kg, augmented the incidence of apoptotic hepatocytes 5-fold. Equimolar doses of TGF-beta 1 latency-associated protein complex were ineffective. These studies suggest that TGF-beta 1 is involved in the initiation of apoptosis in the liver and that the mature form of TGF-beta 1 is the active principle.
Nucleotide Sequence and Expression of the Feline Vascular Endothelial Growth Factor. (2002)

Vascular endothelial growth factor (VEGF) is an angiogenic factor which targets vascular endothelial cells. In this study, cDNA encoding a feline VEGF (fVEGF) isoform was cloned from a feline lymphoid tumor cell line and sequenced. The fVEGF cDNA contained an open reading frame of 567 nucleotides coding for a polypeptide of 163 amino acids with a putative signal peptide of 26 amino acids. The predicted fVEGF amino acid sequence shared 98.4, 94.2 and 94.2% homology with the sequences of canine, bovine and human VEGF, respectively. Though predicted fVEGF polypeptide was two amino acid residues shorter than human VEGF165, a potential glycosylation site and regions critical for receptor binding were conserved in all the species examined. Transient expression of fVEGF in mammalian cells resulted in secretion of VEGF which could be detected by antibodies against human VEGF165. Furthermore, wide expression of fVEGF mRNA was observed in various feline tissues using RT-PCR methods.
The role of nitric oxide chemistry in cancer treatment. (1998)

Over the last decade the role of nitric oxide (NO) in various disease states has become apparent. In cancer, NO plays a variety of roles which are at times contradictory. On one hand, NO is involved in different etiological mechanisms as well as promoting tumor growth. Yet, NO derived from leukocytes plays a seminal role in their tumoricidal activity. In cancer treatment, NO also has diverse effects. Whereas in vitro, NO can enhance the cytotoxic efficacy of some chemotherapeutic agents as well as radiation, NO donors can provide whole body protection against these same agents. This manuscript will discuss some mechanisms involved with NO and cancer treatment modalities and the potential application of these findings to cancer therapy.
Fatty liver hepatitis (steatohepatitis) and obesity: An autopsy study with analysis of risk factors (1990)

Steatohepatitis (fatty liver hepatitis), histologically identical to alcoholic disease, occurs in some obese patients after jejunoileal bypass. A similar lesion occurs rarely in obese patients without bypass surgery, but the risk factors are poorly understood. Hepatic steatosis, steatohepatitis and fibrosis were sought in 351 apparently nonalcoholic patients at autopsy and various risk factors were evaluated. Incidence of steatosis and steatohepatitis correlated with the degree of obesity. Steatohepatitis was found in 18.5% of markedly obese patients and 2.7% of lean patients. Additional risk factors for steatohepatitis were type II diabetes, weight loss in the preterminal period shortly before death and intravenous glucose therapy in the last week of life. Severe fibrosis was found in 13.8% of markedly obese patients and in 6.6% of lean patients; this difference was largely explained by the higher prevalence of diabetes in obese groups. The risk factors defined in this study are known to be associated with abnormalities of free fatty acid metabolism. Obesity, type II diabetes and intravenous glucose therapy are associated with hyperinsulinemia, which may inhibit fatty acid oxidation. Obesity and weight loss increase the presentation of fatty acids to the liver. Similar metabolic changes may occur in obese patients after jejunoileal bypass surgery. Thus this study supports the hypothesis that fatty acids have a role in the hepatocellular necrosis found in some obese individuals.
Inhibition of endothelial cell proliferation by gamma-interferon. (1987)

Endothelial cell growth factor (ECGF) is a potent polypeptide mitogen for endothelial cells and fibroblasts. The mitogenic effects of ECGF are inhibited by the lymphokine gamma-interferon (gamma-IFN) in a dose-dependent manner. Gamma-IFN also induces a unique change in endothelial cell morphology which is maximally expressed in the presence of ECGF. The antiproliferative and phenotypic modulatory effects of gamma-IFN on endothelial cells are reversible. Inhibition of ECGF-induced endothelial cell proliferation by gamma-IFN is accompanied by a concentration- and time-dependent decrease in binding of 125I-ECGF to the endothelial cell surface. Scatchard analyses of the binding data in the presence and absence of gamma-IFN demonstrate a decrease in the number of ECGF-binding sites rather than a decrease in ligand affinity for the receptor. Cross-linking experiments with disuccinimidyl suberate demonstrate a decrease in the 170,000 Mr cross-linked receptor-ligand complex. These data suggest that gamma-IFN inhibits endothelial cell proliferation by a mechanism which involves growth factor receptor modulation.
CD4+CD25+ regulatory T cells in rheumatoid arthritis: Differences in the presence, phenotype, and function between peripheral blood and synovial fluid (2004)

We demonstrate that CD4(+)CD25(+) regulatory T cells are present and functional in patients with RA, with higher numbers of regulatory T cells with increased suppressive activity found in SF compared with PB. These findings suggest a negative feedback system that is active at the site of inflammation. The balance between activated responder and regulatory T cells appears to influence the extent of immunoregulation in RA.
Accumulation of Platelets and Eosinophils in Baboon Lung after Paf-acether Challenge: Inhibition by Ketotifen (1988)

Intratracheal administration of platelet-activating factor (paf-acether) induced transient bronchoconstriction in baboons. Using an automated isotopic monitoring system, we found that intratracheal administration of paf-acether also elicited transient accumulation of platelets labeled with 111In oxine within the pulmonary vasculature after the increase in maximal peak inspiratory pressure. Bronchoalveolar eosinophilia were inhibited by prophylactic administration of the antiasthma drug ketotifen but not by pyribenzamine, suggesting that the effects of ketotifen are unrelated to H-1 receptor antagonism. Platelet accumulation was not affected by ketotifen or pyribenzamine. This study suggests that paf-acether may be a mediator of the eosinophil recruitment in bronchial asthma and that inhibition of this phenomenon by ketotifen may contribute to the therapeutic efficacy of this drug.
Proofreading-defective DNA polymerase II increases adaptive mutation in Escherichia coli. (1995)

The role of Escherichia coli DNA polymerase (Pol) II in producing or avoiding mutations was investigated by replacing the chromosomal Pol II gene (polB+) by a gene encoding an exonuclease-deficient mutant Pol II (polBex1). The polBex1 allele increased adaptive mutations on an episome in nondividing cells under lactose selection. The presence of a Pol III antimutator allele (dnaE915) reduced adaptive mutations in both polB+ cells and cells deleted for polB (polB delta 1) to below the wild-type level, suggesting that both Pol II and Pol III are synthesizing episomal DNA in nondividing cells but that in wild-type cells Pol III generates the adaptive mutations. The adaptive mutations were mainly -1 frame-shifts occurring in short homopolymeric runs and were similar in wild-type, polB delta 1, and polBex1 strains. Mutations produced by both Pol III and Pol II ex1 were corrected by the mutHLS mismatch repair system.
Proprotein Covertases Are Responsible for Proteolysis and Inactivation of Endothelial Lipase (2005)

Plasma lipoprotein metabolism is tightly regulated by several members of the triglyceride lipase family, including endothelial lipase (EL) and lipoprotein lipase (LPL). Our previous work suggested that EL is proteolytically processed. In this report, we have used a combination of epitope tagging, mutagenesis, and N-terminal sequencing to determine the precise location of the cleavage site within EL. The cleavage occurs immediately after the sequence RNKR, a known recognition sequence for the proprotein convertase (PC) family. We demonstrate that some PCs, but not all, can proteolytically cleave EL at this site and thereby directly regulate EL enzymatic activity through modulating EL cleavage. Furthermore, specific knockdown of individual PCs proves that PCs are the proteases that cleave EL in human endothelial cells. Interestingly, a homologous site in LPL is also cleaved by PCs. This action is unusual for PCs, which are traditionally known as activators of pro-proteins, and highlights a potential role of PCs in lipid metabolism through their proteolytic processing of lipases.
A new monoclonal antibody (KB61) recognizing a novel antigen which is selectively expressed on a subpopulation of human B lymphocytes. (1986)

The present paper describes a new monoclonal antibody (KB61) raised against hairy cell leukaemia cells. Antibody KB61 recognizes a molecule of approximately 40,000 molecular weight on human B cells. It reacts with B lymphocytes in the peripheral blood, in primary lymphoid follicles, in the mantle zone of secondary follicles, in interfollicular areas and in splenic marginal zone areas. However, germinal centre lymphoid cells do not express the antigen recognized by antibody KB61. The antibody shows limited reactivity outside the lymphoid system, i.e. polymorphs, tissue macrophages endothelial cells in the hepatic sinusoids. Antibody KB61 discriminates between different types of B-cell malignancies, reacting with the neoplastic cells in hairy cell leukaemia, chronic lymphocytic leukaemia (of B-cell type), prolymphocytic leukaemia and centrocytic lymphoma, but not with acute lymphoblastic leukaemia, germinal centre-derived lymphomas (other than centrocytic), Burkitt's lymphoma and lymphoblastic lymphoma. Antibody KB61 may be of value in the study of B-cell subpopulations and in the differential diagnosis of B-cell neoplasms.
Dose tailoring strategies in haemodialysis patients: a discussion of case histories (2005)

Tailoring of the epoetin dose to the needs, clinical condition and circumstances of individual patients with renal anaemia offers potential for optimizing the benefits and costs of epoetin therapy. This can be achieved through alterations to dosing frequency, administration route and/or delivery device. Two case histories are presented to illustrate dose tailoring of epoetin therapy in daily clinical practice. The first patient was a man aged 23 years with renal failure secondary to vasculitis. Haemoglobin (Hb) levels were stable during treatment with subcutaneous (s.c.) epoetin-beta. Switching to intravenous (i.v.) epoetin-beta required, after a 5 month period of complex dose adjustments, a 50% increase in the dose of epoetin-beta to maintain Hb levels. The second patient was a woman aged 50 years with diabetic nephropathy. She self-administered epoetin-beta via the Reco-Pen device to maintain stable Hb levels. Epoetin-beta is approved for administration at dosing frequencies ranging from three times weekly to once every 2 weeks, is safe and effective whether administered by the s.c. or i.v. route and is available in a range of delivery devices. Epoetin-beta therapy can be easily tailored according to the needs, preferences and circumstances of individual patients, thereby maximizing treatment outcomes.
Bioactive Oleanane, Lupane and Ursane Triterpene Acid Derivatives (2012)

Betulinic, ursolic and oleanolic acids isolated from the aerial parts of Eriope blanchetii (Lamiaceae) were subjected to different esterification reactions, yielding 12 C-3 position ester derivatives. All compounds were identified using spectroscopic techniques, such as IR, 1H-NMR and MS. The derivatives were further investigated for their antioxidant level, Artemia salina lethality and antimicrobial activity.
Sunlight‐induced mutagenicity of a common sunscreen ingredient (1993)

We have tested the mutagenicity of a UV-B sunscreen ingredient called Padimate-O or octyl dimethyl PABA, which, chemically speaking, is identical to an industrial chemical that generates free radicals when illuminated. It is harmless in the dark but mutagenic in sunlight, attacking DNA directly. A commercial sunscreen containing Padimate-O behaves in the same way. UV-A in sunlight also excites Padimate-O, although less than UV-B. Some related compounds, including a known carcinogen, behave similarly. As mutagens may be carcinogenic, our results suggest that some sunscreens could, while preventing sunburn, contribute to sunlight-related cancers.
Chemical grafting of sulfobetaine onto poly(ether urethane) surface for improving blood compatibility (2003)

Abstract Poly(ether urethane)s (PEUs) are widely used as blood‐contact biomaterials because of their good biocompatibility and mechanical properties. Nevertheless, their blood compatibility is still not adequate for more demanding applications. Surface modification is an effective way to improve blood compatibility and retain bulk properties of biomaterials. The purpose of the present study was to design and synthesis a novel non‐thrombogenic biomaterial by modifying the surface of PEU with zwitterionic monomer. In this study, sulfobetaine was grafted onto PEU surface through the following reaction steps: (1) Poly(propylene oxide) (PPO) was reacted at both chain ends with hexamethylene diisocyanate (HDI), and OCN–PPO–NCO was obtained; (2) OCN–PPO–NCO was reacted at one chain end with N , N ‐dimethylethanolamine (DMEA) and OCN–PPO–N(CH 3 ) 2 was formed; (3) the sulfobetaine was prepared by a ring‐opening reaction between OCN–PPO–N(CH 3 ) 2 and 1,3‐propanesultone (PSu); (4) the sulfobetaine was grafted onto PEU surface by the reaction between NCO and the N–H bonds of PEU. The surface composition of films and the hydrophilicity on the PEU surface were investigated by X‐ray photoelectron spectroscopy analysis and contact angle measurements, respectively. The blood compatibility of PEU was evaluated by platelet‐rich plasma contact experiments and the results were observed by scanning electron microscopy. The state of platelet adhesion and shape variation for the attached platelets was described. The modified surface showed excellent blood compatibility, featured by low platelet adhesion. Copyright © 2003 Society of Chemical Industry
Herpes Simplex Virus Type 1 Strain HSV1716 Grown in Baby Hamster Kidney Cells Has Altered Tropism for Nonpermissive Chinese Hamster Ovary Cells Compared to HSV1716 Grown in Vero Cells (2005)

Chinese hamster ovary (CHO) cells are traditionally regarded as nonpermissive cells for herpes simplex virus type 1 (HSV-1) infection as they lack the specific entry receptors, and modified CHO cells have been instrumental in the identification of HSV-1 receptors in numerous studies. In this report we demonstrate that the HSV-1 strain 17+ variant HSV1716 is able to infect unmodified CHO cells but only if the virus is propagated in baby hamster kidney (BHK) cells. Infection of CHO cells by BHK-propagated HSV1716 results in expression of immediate-early, early, and late viral genes, and infectious progeny virions are produced. In normally cultured CHO cells, up to a maximum of 50% of cells were permissive for BHK-propagated HSV1716 infection, with 24 h of serum starvation increasing this to 100% of CHO cells, suggesting that the mechanism used by BHK-propagated virus to infect CHO cells was cell cycle dependent. The altered tropism of HSV1716 was also evident in another nonpermissive mouse melanoma cell line and is an exclusive property resulting from propagation of the virus using BHK cells, as viruses propagated on Vero, C8161 (a human melanoma cell line), or indeed, CHO cells were completely unable to infect either CHO or mouse melanoma cells.
The avidity of specific IgM detected in primary rubella and reinfection (1990)

An IgM capture enzyme-linked immunosorbent assay for rubella-specific IgM was used to assess the avidity of specific IgM by comparing the results obtained with and without a mild protein denaturant in the washing fluid used after incubation of IgM with rubella haemagglutinating antigen. An avidity index (AI) was calculated with AIs less than 50% considered to indicate low avidity. Sera from recent primary rubella, rubella reinfection and from patients persistently reactive for specific IgM were tested. Urea and diethylamine (DEA) were compared as the protein denaturants. Twenty-six of 28 sera from cases of primary rubella gave an AI less than 50% with DEA, compared with 25 of 28 with urea. Seventeen of 20 sera from cases of reinfection gave an AI greater than 50% with DEA whereas only 14 of 20 had a similarly high avidity with urea. Eight of 10 sera from 4 cases of persistent specific IgM reactivity gave AIs greater than 50% with DEA, although this was reduced to 5 when urea was used. Thus a difference has been demonstrated between the avidity of specific IgM in primary infection from that demonstrated after a secondary antigenic challenge (reinfection). This may help in serologically distinguishing primary infection from reinfection.
Improvement of HbA1c and Blood Glucose Stability in IDDM Patients Treated With Lispro Insulin Analog in External Pumps (1998)

When used in external pumps, LP provides better glycemic control and stability than regular insulin and does not increase the frequency of hypoglycemic episodes.
A printable form of silicon for high performance thin film transistors on plastic substrates (2004)

Free-standing micro- and nanoscale objects of single crystal silicon can be fabricated from silicon-on-insulator wafers by lithographic patterning of resist, etching of the exposed top silicon, and removing the underlying SiO2 to lift-off the remaining silicon. A large collection of such objects constitutes a type of material that can be deposited and patterned, by dry transfer printing or solution casting, onto plastic substrates to yield mechanically flexible thin film transistors that have excellent electrical properties. Effective mobilities of devices built with this material, which we refer to as microstructured silicon (μs-Si), are demonstrated to be as high as 180cm2∕Vs on plastic substrates. This form of “top down” microtechnology might represent an attractive route to high performance flexible electronic systems.
Fibroblast Growth Factor 21 Improves Insulin Resistance and Ameliorates Renal Injury in db/db Mice (2013)

Despite the emerging importance of fibroblast growth factor 21 (FGF21) as a metabolic hormone regulating energy balance, its direct effects on renal function remain unexplored. FGF21 was injected ip daily for 12 weeks into db/db mice. Compared with control vehicle injection, FGF21 treatment significantly improved lipid profiles and insulin resistance and resulted in significantly higher serum adiponectin levels. In contrast, serum insulin and 8-isoprostane levels were significantly decreased. Interestingly, FGF21 and its receptor components in the kidneys were found to be significantly up-regulated in db/db mice, which suggests an FGF21-resistant state. FGF21 treatment significantly down-regulated FGF21 receptor components and activated ERK phosphorylation. FGF21 administration also markedly decreased urinary albumin excretion and mesangial expansion and suppressed profibrotic molecule synthesis. Furthermore, FGF21 improved renal lipid metabolism and oxidative stress injury. In cultured renal cells, FGF21 was mainly expressed in mesangial cells, and knockdown of FGF21 expression by stealth small interfering RNA further aggravated high-glucose-induced profibrotic cytokine synthesis in mesangial cells. Our results suggest that FGF21 improves insulin resistance and protects against renal injury through both improvement of systemic metabolic alterations and antifibrotic effects in type 2 diabetic nephropathy. Targeting FGF21 could therefore provide a potential candidate approach for a therapeutic strategy in type 2 diabetic nephropathy.
Role of medical history in brain tumour development. Results from the international adult brain tumour study (1999)

In an international population-based case-control study carried out in 8 centres in 6 countries, we investigated the role of specific medical conditions in the aetiology of brain tumours in adults. Recruited were 1,178 glioma and 331 meningioma cases and 2,493 age- and gender-matched population controls. Only medical conditions occurring at least 2 years before brain tumour diagnosis were considered. Relative risks (RRs) and 95% confidence intervals (CIs) were estimated using a conditional logistic regression model. Heterogeneity between centres was tested. No association between meningioma and previous medical conditions was observed. For glioma, there was an increased risk associated with epilepsy (RR = 6.55, 95% CI 3.40-12.63), but this was considerably weaker for epilepsy of more than 20 years duration. The risk remained elevated after adjustment for use of anti-epileptic drugs. There was a statistically significant inverse association between glioma and all allergic diseases combined (RR = 0.59, 95% CI 0.49-0.71); this was also observed for specific allergic conditions, namely, asthma and eczema. Subjects who reported a history of infectious diseases (e.g., colds, flu) showed a 30% reduction in risk (RR = 0.72, 95% CI 0.61-0.85). The decreased risks for glioma in subjects reporting a history of allergic conditions or infectious diseases may indicate an influence of immunological factors on the development of glioma. The association between glioma and epilepsy has to be interpreted cautiously and needs further investigation.