gebhart/patrepeval huggingface dataset:
Cell fusion induced by the murine leukemia virus envelope glycoprotein (1993)

To determine whether ecotropic murine leukemia virus (MuLV) envelope glycoproteins are sufficient to cause cell-to-cell fusion when expressed in the absence of virus production, we used an ecotropic MuLV, AKV, to construct env expression vectors that lack the gag and pol genes. The rat cell line XC, which undergoes cell-to-cell fusion upon infection with ecotropic MuLV, was transfected with wild-type env expression vectors, and high levels of syncytium formation resulted. Transfection of the murine cell line NIH 3T3 with expression vectors containing the wild-type or mutated env region did not result in syncytium formation. Immunoprecipitation analysis of the envelope glycoproteins expressed in NIH 3T3 and XC cells showed that the mature surface glycoprotein expressed in XC cells was of a much lower apparent molecular weight than that expressed in NIH 3T3 cells. Further characterization showed that most if not all of this difference was the result of differences in glycosylation. Finally, site-directed mutagenesis was used to introduce several conservative and nonconservative changes into the amino-terminal region of the transmembrane protein. Analysis of the effect of these mutations confirmed that this region is a fusion domain.
Typhoid Fever in the United States, 1985-1994 (1998)

American travelers to less industrialized countries, especially those traveling to the Indian subcontinent, continue to be at risk for typhoid fever. Antimicrobial resistance has increased, and a quinolone or third-generation cephalosporin may be the best choice for empirical treatment of typhoid fever.
A Message-Passing Approach to Distributed Resource Allocation in Uplink DFT-Spread-OFDMA Systems (2011)

In this paper, we consider the problem of resource allocation in the DFT-Spread-OFDMA (DFT-S-OFDMA) uplink. We show that the resource allocation problem can be formulated as a set packing problem, which in general is NP-hard. We propose polynomial-time message-passing based algorithms, one of which is guaranteed to yield a solution that is within a constant fraction of the optimal solution and is also asymptotically optimal in the limit as the number of subcarriers in the system goes to infinity. The message-passing based algorithm is also extended to solve the resource allocation problem over a multi-cell uplink in a distributed fashion. Our algorithms account for finite input alphabets and non-ideal practical outer codes. Extensive simulations are performed to assess the performance of the proposed algorithms and it is shown that they yield near-optimal solutions at a low complexity and with a low memory requirement.
Free circulating soluble CD52 as a tumor marker in chronic lymphocytic leukemia and its implication in therapy with anti‐CD52 antibodies (2004)

These data not only demonstrated that sCD52 was detectable and useful in the staging and monitoring of patients with CLL, but also showed that sCD52 formed immune complexes with alemtuzumab and may influence the efficacy and toxicity of alemtuzumab therapy.
Synchronization Signal Design for OFDM Based On Time-Frequency Hopping Patterns (2007)

In an OFDM system, channel estimation can be considered as sampling the time-frequency response of the channel through a number of known pilot symbols placed across the time-frequency plane. Sampling theory dictates that the pilot insertion frequency must be above the Nyquist rates in both time and frequency to avoid aliasing of the delay-Doppler response. Based on the regularly spaced pilot pattern, we can derive alternative patterns that preserve the non-aliasing property by hopping the scan lines in either time domain or frequency domain, but not both. From this extended set of patterns, we find ones with properties that, in addition to channel estimation, can achieve responsively other synchronization tasks such as initial time-frequency offset estimation and device identification. The ambiguity function analysis frequently used in radar signal design leads to a periodic time-hopping pattern based on the costas array that has minimal coincidences with its circular time-frequency shifts, which can be used for the identification of multiple devices. The hopping in time also greatly increases the pilot's time support, thus enabling the quick initial acquisition of timing and frequency offset with very short observation.
Early and Late Complications After Radiofrequency Ablation of Malignant Liver Tumors in 608 Patients (2004)

Hepatic tumor RFA can be performed with low mortality and morbidity rates. Though relatively rare, late complications can develop and physicians performing hepatic RFA must be cognizant of these delayed treatment-related problems.
Loss of Growth Regulation by Transforming Growth Factor - β (TGF-β) in Human Cancers: Studies on Endometrial Carcinoma (1999)

Members of the Transforming Growth Factor-beta (TGF-beta) family are one of the few endogenous inhibitors of cell growth. As uncontrolled cellular proliferation is a hallmark of cancer, an important question to address is how cancer cells escape normal growth regulatory mechanisms to become malignant. In this context, components of the TGF-beta growth response pathway are considered to be tumor suppressor genes, as absence of one or more of TGF-beta receptor and signaling proteins cause loss of cell growth regulation through an inability to regulate proteins that directly block cells in G1 phase of the cell cycle. Endometrial carcinoma (ECA) provides an excellent paradigm to study the changes that accompany loss of TGF-beta-mediated growth, control as a function of neoplastic development, since it is generally preceded by complex hyperplasia. Type 1 ECA is characterized as an estrogen-induced cancer, which responds well to progestin therapy. Since it has become increasingly evident that steroids can regulate growth through growth factors, ECA is also an ideal model for investigating the role for gonadal steroids in the loss of TGF-beta growth regulation in the etiopathogenesis of ECA. Thus, hormonal carcinogenesis adds another level of complexity in studying loss of growth regulation in human cancers. The purpose of this review is to 1) provide the most current background information on how TGF-beta functions including its activation, receptors, signal transduction mechanisms, and control of the cell cycle. 2) present recent information that shows how malignant cells subvert the growth inhibitory effects of TGF-beta by incurring defects in every aspect of the pathway that mediates the TGF-beta growth inhibitory response, and 3) describe the putative role for TGF-beta in the oncogenesis of ECA, provided primarily by the results from our laboratory. Understanding the molecular events involved in TGF-beta function in normal cells and its lack of function in tumor cells should identify novel therapeutic targets in human cancers.
PHARMACOLOGIC ACTION OF SOME OPHTHALMIC DRUGS (1947)

DESPITE the fact that most drugs used in ophthalmology are applied directly to the eye, information about their absorption from the surface of the globe is scanty. Only in the case of some of the latest additions to ophthalmic medicine, the sulfonamide drugs and penicillin, has the problem of absorption from the site of their application been systematically studied. It might be expected, since the conjunctiva is not, like the intestinal tract, provided with special mechanisms for absorption, that absorption from its surface would be very poor. However, as ophthalmologists have long known, it is a good absorbing surface for many drugs. Satisfactory effects are obtained after the local instillation of miotics, mydriatics, cycloplegics, anti-infectives, anesthetics and others. Macht<sup>1</sup>showed that after apomorphine had been placed on a dog's eye vomiting occurred in a few minutes, indicating exceedingly prompt absorption of that drug from the conjunctival sac into the
Tissue-specific regulation of glucocorticoid receptor mRNA by dexamethasone. (1987)

The effect of glucocorticoids on tissue-specific regulation of glucocorticoid receptor mRNA was studied in intact and adrenalectomized rats. Glucocorticoid receptor mRNA was examined by Northern blot hybridization and quantitated by slot blot hybridization using a glucocorticoid cRNA probe. Glucocorticoid receptor mRNA was greatest in the lung with the relative levels in other tissues as follows: spleen, 70%; brain, 55%; liver, 50%; kidney, 43%; heart, 35%; adrenal, 13%; and testis only 8%. A tissue-specific difference in glucocorticoid receptor mRNA accumulation was found after adrenalectomy. There was little change in glucocorticoid receptor mRNA levels in liver and lung, but the brain and kidney demonstrated a 40 and 80% increase in mRNA, respectively. In contrast, dexamethasone treatment resulted in a consistent decrease of 40-60% in the accumulation of glucocorticoid receptor mRNA in all tissues studied. These results provide in vivo evidence for the autoregulation of the glucocorticoid receptor by its homologous ligand and demonstrate the existence of tissue-specific regulation of the glucocorticoid receptor mRNA levels in states of glucocorticoid excess and depletion.
Construction of vaccinia virus recombinants expressing several measles virus proteins and analysis of their efficacy in vaccination of mice (1992)

Measles virus genes encoding the haemagglutinin (HA), fusion protein (F) or nucleoprotein (NP) have been inserted into the vaccinia virus genome either alone or in various combinations. In each case the measles virus genes were expressed from the 7.5K promoter and were incorporated into the thymidine kinase (tk) or K1L loci of the Copenhagen strain of vaccinia virus. Cells infected by the recombinants synthesized measles virus proteins indistinguishable from those induced in measles virus-infected cells. However, in some instances the level of expression in cells infected by recombinants expressing more than one measles virus gene was reduced when compared to those encoding a single gene. The sera from mice immunized with recombinants containing either HA, HA.F, HA.NP or HA.F.NP had similar levels of measles virus neutralizing antibodies which remained constant throughout a 7 month period. Analysis of these sera by immunoprecipitation of radiolabelled measles virus confirmed the presence of specific antibody to each of the antigens where appropriate. The introduction of the measles virus genes into the K1L and the tk sites despite attenuating the virus for mice by 10-fold and 1000-fold respectively did not affect the vaccination efficiency, i.e. ability to induce measles virus antibody and protect mice. Vaccination of BALB/c (H2d) mice with HA and F, but not NP, recombinants completely protected the animals against a lethal measles virus challenge. In contrast, although the HA recombinant protected CBA (H2k) mice, the F recombinant did so poorly. However, by immunizing CBA mice with a recombinant expressing both F and NP, protection was increased to more than 75%. Our findings demonstrate the ability of three measles virus antigens expressed from the vaccinia virus genome alone or in combination to contribute to protective immunity against measles virus infection of mice. They also suggest that the association of measles virus antigens in a single recombinant DNA vaccine could be beneficial to overcome host-related restriction of the immune response to particular antigens.
Oxygen-regulated Transferrin Expression Is Mediated by Hypoxia-inducible Factor-1 (1997)

Transferrin (Tf) is a liver-derived iron transport protein whose plasma concentration increases following exposure to hypoxia. Here, we present a cell culture model capable of expressing Tf mRNA in an oxygen-dependent manner. A 4-kilobase pair Tf promoter/enhancer fragment as well as the 300-base pair liver-specific Tf enhancer alone conveyed hypoxia responsiveness to a heterologous reporter gene construct in hepatoma but not HeLa cells. Within this enhancer, a 32-base pair hypoxia-responsive element was identified, which contained two hypoxia-inducible factor-1 (HIF-1) binding sites (HBSs). Mutation analysis showed that both HBSs function as oxygen-regulated enhancers in Tf-expressing as well as in non-Tf-expressing cell lines. Mutation of both HBSs was necessary to completely abolish hypoxic reporter gene activation. Transient co-expression of the two HIF-1 subunits HIF-1alpha and aryl hydrocarbon receptor nuclear translocator (ARNT)/HIF-1beta resulted in enhanced reporter gene expression even under normoxic conditions. Overexpression of a dominant-negative ARNT/HIF-1beta mutant reduced hypoxic activation. DNA binding studies using nuclear extracts from the mouse hepatoma cell line Hepa1 and the ARNT/HIF-1beta-deficient subline Hepa1C4, as well as antibodies raised against HIF-1alpha and ARNT/HIF-1beta confirmed that HIF-1 binds the Tf HBSs. Mutation analysis and competition experiments suggested that the 5' HBS was more efficient in binding HIF-1 than the 3' HBS. Finally, hypoxic induction of endogenous Tf mRNA was abrogated in Hepa1C4 cells, confirming that HIF-1 confers oxygen regulation of Tf gene expression by binding to the two HBSs present in the Tf enhancer.
Structure-Activity Relationships in Distamycin A Analogues: Effect of Alkyl Groups on the Pyrrole Nitrogen at the Non-amidine End of the Molecule Combined with Methyl Elimination in the Following Ring. (1986)

Distamycin A analogues 5a-f (R = CnH2n+1, n = 0-5) were synthesized using our previous strategy with some improved modifications and screened for their effects on herpes simplex virus (HSV-1). Virus yield assays show that 5a-5d were potent antiviral agents whereas 5e and 5f had lower activity. Considerable cellular toxicity was however observed for 5a-5c. Thus 5d combining significant antiviral activity with moderate cellular toxicity seems to be the most promising derivative in this series.
Development of Methods for Somatic Cell Gene Therapy Directed Against Viral Diseases, Using Retroviral Vectors Carrying the Murine or Human Interferon-β Coding Sequence: Establishment of the Antiviral State in Human Cells (1993)

We are developing methods for somatic cell gene therapy directed against chronic and fatal virus infections, such as acquired immunodeficiency (AIDS), by transforming cells with a constitutively expressed interferon (IFN) coding sequence. Previous work from our laboratory has shown that stable antiviral expression (SAVE) can be obtained in murine BALB/c 3T3 cells and human U937 cells transformed with plasmids carrying either the murine or the human IFN-beta coding sequence placed under the expression control of a 0.6-kb Xho II-Nru I promoter region of the murine H-2Kb major histocompatibility complex (MHC) gene (Macé et al., 1991; Seif et al., 1991). In the present paper, we report the construction of murine (Mu) and human (Hu) IFN-beta-expressing retroviral vectors (pMPZen-MuIFN beta, pHMB-KbMuIFN beta) and the problems encountered. Because of the murine origin of commonly used packaging cells and the species specificity of IFN, it was evident that placing the murine IFN-beta sequence under constitutive expression control could result in the production of Mu IFN in the murine packaging system, and thereby lead to decreased vector production and also to enhanced resistance of target cells. Using a packaging cell line that releases a beta-galactosidase-expressing vector, we show that, as expected, Mu IFN-alpha/beta decreases vector production of murine packaging cells and also inhibits the transformation of target NIH-3T3 cells with this vector, but the presence of anti-Mu IFN antibodies rescues the viral titer of the packaging cells and restores the sensitivity of target cells to virus transformation. However, the same antibody treatment is unable to rescue the viral titer of psi-2 packaging cells producing autocrine Mu IFN-beta encoded by the pMPZen-MuIFN beta and pHMB-KbMuIFN beta vectors. Because of the species specificity of IFN, this problem is circumvented with the pMFG-HuIFN beta vector carrying the human IFN-beta sequence. In spite of the production of Hu IFN, murine psi-CRIP packaging cells are able to release retroviral vectors expressing Hu IFN-beta, and these amphotropic vectors can transform human MRC-5 cells and confer to these cells an enhanced resistance to vesicular stomatitis virus (VSV) infection.
The synthesis of 2,3,4,6-tetrahydro-5-hydroxy-2,6-dimethyl-1H-pyrido[4,3-b]carbazole; attempts to synthesise 2,3,4,10-tetrahydro-5-hydroxy-2-methyl-1H-pyrido[3,4-b]carbazole (1979)

The synthesis of 1-methyl-3-(dimethylaminomethyl)indol-2-yl, 3-(dimethylaminomethyl)indol-2-yl, 2-(dimethylaminomethyl)indol-3-yl, and 2-methoxymethylindol-3-yl 1,2,5,6-tetrahydro-1-methylpyridin-4-yl ketones is described. Although each of these could be isomerised to the corresponding cyclic enamine (2-piperideine), only in the first case could the result of intramolecular β-alkylation of the enamine be obtained, i.e. 2,3,4,6-tetrahydro-5-hydroxy-2,6-dimethyl-1H-pyrido[4.3-b]carbazole (9a).
Tissue Inhibitor of Metalloproteinase (TIMP)-2 Acts Synergistically with Synthetic Matrix Metalloproteinase (MMP) Inhibitors but Not with TIMP-4 to Enhance the (Membrane Type 1)-MMP-dependent Activation of Pro-MMP-2 (2000)

The membrane-type 1 matrix metalloproteinase (MT1-MMP) has been shown to be a key enzyme in tumor angiogenesis and metastasis. MT1-MMP hydrolyzes a variety of extracellular matrix components and is a physiological activator of pro-MMP-2, another MMP involved in malignancy. Pro-MMP-2 activation by MT1-MMP involves the formation of an MT1-MMP.tissue inhibitors of metalloproteinases 2 (TIMP-2). pro-MMP-2 complex on the cell surface that promotes the hydrolysis of pro-MMP-2 by a neighboring TIMP-2-free MT1-MMP. The MT1-MMP. TIMP-2 complex also serves to reduce the intermolecular autocatalytic turnover of MT1-MMP, resulting in accumulation of active MT1-MMP (57 kDa) on the cell surface. Evidence shown here in Timp2-null cells demonstrates that pro-MMP-2 activation by MT1-MMP requires TIMP-2. In contrast, a C-terminally deleted TIMP-2 (Delta-TIMP-2), unable to form ternary complex, had no effect. However, Delta-TIMP-2 and certain synthetic MMP inhibitors, which inhibit MT1-MMP autocatalysis, can act synergistically with TIMP-2 in the promotion of pro-MMP-2 activation by MT1-MMP. In contrast, TIMP-4, an efficient MT1-MMP inhibitor, had no synergistic effect. These studies suggest that under certain conditions the pericellular activity of MT1-MMP in the presence of TIMP-2 can be modulated by synthetic and natural (TIMP-4) MMP inhibitors.
Therapeutic targeting of extracellular DNA improves the outcome of intestinal ischemic reperfusion injury in neonatal rats (2017)

Thrombosis and inflammation cooperate in the development of intestinal infarction. Recent studies suggest that extracellular DNA released by damaged cells or neutrophils in form of extracellular traps (NETs) contributes to organ damage in experimental models of ischemia-reperfusion injury. Here we compared the therapeutic effects of targeting fibrin or extracellular DNA in intestinal infarction after midgut volvulus in rats. Following iatrogenic midgut volvulus induction for 3 hours, we treated animals with a combination of tissue plasminogen activator (tPA) and low molecular weight heparin (LMWH) to target fibrin or with DNase1 to degrade extracellular DNA. The therapeutic effects of tPA/LMWH and DNase1 were analyzed after 7 days. We observed that both therapeutic interventions ameliorated tissue injury, apoptosis, and oxidative stress in the intestine. DNase1, but not tPA/LMWH, reduced intestinal neutrophil infiltration and histone-myeloperoxidase-complexes, a surrogate marker of NETs, in circulation. Importantly, tPA/LMWH, but not DNase1, interfered with hemostasis as evidenced by a prolonged tail bleeding time. In conclusion, our data suggest that the therapeutic targeting of fibrin and extracellular DNA improves the outcome of midgut volvulus in rats. DNase1 therapy reduces the inflammatory response including NETs without increasing the risk of bleeding. Thus, targeting of extracellular DNA may provide a safe therapy for patients with intestinal infarction in future.
Cellular and molecular events leading to mitochondrial toxicity of 1-(2-deoxy-2-fluoro-1-beta-D-arabinofuranosyl)-5-iodouracil in human liver cells. (1995)

We have explored the mechanism(s) related to FIAU-induced liver toxicity, particularly focusing on its effect on mitochondrial function in a human hepatoma cell line-HepG2. The potential role of FMAU and FAU, metabolites detected in FIAU-treated patients were also ascertained. FIAU and FMAU inhibited cell growth and were effectively phosphorylated. A substantial increase in lactic acid production in medium of cells incubated with 1-10 microM FIAU or FMAU was consistent with mitochondrial dysfunction. Slot blot analysis demonstrated that a two week exposure to 10 microM FIAU or FMAU was not associated with a decrease in total mitochondrial (mt) DNA content. However, FIAU and FMAU were incorporated into nuclear and mtDNA and relative values suggest that both compounds incorporate at a much higher rate into mtDNA. Electron micrographs of cells incubated with 10 microM FIAU or FMAU revealed the presence of enlarged mitochondria with higher cristae density and lipid vesicles. In conclusion, these data suggest that despite the lack of inhibition of mtDNA content, incorporation of FIAU and FMAU into mtDNA of HepG2 cells leads to marked mitochondrial dysfunction as evidenced by disturbance in cellular energy metabolism and detection of micro- and macrovesicular steatosis.
The functional BPV-1 E2 trans-activating protein can act as a repressor by preventing formation of the initiation complex. (1991)

The products encoded by the E2 open reading frame of the papillomaviruses are DNA-binding transcription factors involved in the positive or negative regulation of multiple viral promoters. To further understand the mechanisms by which the same transcription factor may act differentially, the full-length BPV-1 E2 protein was expressed and purified from yeast and assayed in vitro for its capacity to modulate transcription. E2 stimulated transcription of the HSV thymidine kinase (TK) promoter when E2-binding sites were positioned in an enhancer configuration approximately 100 bp upstream of the promoter start site. In contrast, the same full-length E2 protein repressed transcription of the HPV-18 E6/E7 P105 promoter. This repression was mediated through binding to the E2 DNA-binding site immediately upstream of the P105 promoter TATA box and could be abrogated by preincubation of the HPV-18 P105 promoter template with the nuclear extract allowing the formation of the preinitiation complex. In vitro DNA-binding experiments with purified E2 and TFIID showed that binding of E2 to its DNA target placed at different positions with respect to the TATA box differentially affects binding of TFIID to its cognate site. In these respects, E2 is similar to the bacteriophage lambda repressor, which can act either as a repressor or an activator of transcription depending on the position of its binding sites relative to the promoter sequences.