gebhart/patrepeval huggingface dataset:
Changing patterns in the incidence of esophageal and gastric carcinoma in the United States (1998)

BACKGROUND Incidence rates for esophageal adenocarcinoma previously were reported to be increasing rapidly, especially among white males. Rates for gastric cardia adenocarcinoma also were observed to be rising, although less rapidly. In this article, the authors update the incidence trends through 1994 and further consider the trends by age group. METHODS Surveillance, Epidemiology, and End Results (SEER) program data were used to calculate age-adjusted incidence rates for esophageal carcinoma by histologic type and gastric adenocarcinoma by anatomic subsite. RESULTS Among white males, the incidence of adenocarcinoma of the esophagus rose > 350% since the mid-1970s, surpassing squamous cell carcinoma around 1990. Rates also rose among black males, but remained at much lower levels. To a lesser extent, there were continuing increases in gastric cardia adenocarcinoma among white and black males, which nearly equaled the rates for noncardia tumors of the stomach in white men. The upward trend for both tumors was much greater among older than younger men. Although the incidence also rose among females, rates remained much lower than among males. CONCLUSIONS Previously reported increases of esophageal adenocarcinoma are continuing, most notably among white males. Cigarette smoking may contribute to the trend through an early stage carcinogenic effect, along with obesity, which may increase intraabdominal pressure and predispose to gastroesophageal reflux disease. Further research into esophageal and gastric cardia adenocarcinoma is needed to clarify the risk factors and mechanisms responsible for the upward trends as well as the racial and gender disparities in incidence. Cancer 1998;83:2049-2053. © 1998 American Cancer Society.
Identification of the Human Methylmalonyl-CoA Racemase Gene Based on the Analysis of Prokaryotic Gene Arrangements (2001)

In this report, we identify the human DL-methylmalonyl-CoA racemase gene by analyzing prokaryotic gene arrangements and extrapolating the information obtained to human genes by homology searches. Sequence similarity searches were used to identify two groups of homologues that were frequently arranged with prokaryotic methylmalonyl-CoA mutase genes, and that were of unknown function. Both gene groups had homologues in the human genome. Because methylmalonyl-CoA mutases are involved in the metabolism of propionyl-CoA, we inferred that conserved neighbors of methylmalonyl-CoA mutase genes and their human homologues were also involved in this process. Subsequent biochemical studies confirmed this inference by showing that the prokaryotic gene PH0272 and its human homologue both encode DL-methylmalonyl-CoA racemases. To our knowledge this is the first report in which the function of a eukaryotic gene was determined based on the analysis of prokaryotic gene arrangements. Importantly, such analyses are rapid and may be generally applicable for the identification of human genes that lack homologues of known function or that have been misidentified on the basis of sequence similarity searches.
Application of a Microcalorimetric Method for Determining Drug Susceptibility in Mycobacterium Species (2011)

Mycobacterium tuberculosis is a global public health concern, particularly with the emergence of drug-resistant strains. Immediate identification of drug-resistant strains is crucial to administering appropriate treatment before the bacteria are allowed to spread. However, developing countries, which are most affected by drug resistance, are struggling to combat the disease without the facilities or funds for expensive diagnostics. Recent studies have emphasized the suitability of isothermal microcalorimetry (IMC) for the rapid detection of mycobacteria. In this study, we investigate its suitability for rapid and reliable M. tuberculosis drug susceptibility testing. Specifically, IMC was used to determine the MICs of three drugs, namely, isoniazid, ethambutol, and moxifloxacin, against three mycobacteria, namely, Mycobacterium smegmatis, Mycobacterium avium, and Mycobacterium tuberculosis. The Richards growth model was used to calculate growth parameters, namely, the maximum bacterial growth rate and the lag phase duration from integrated heat flow-versus-time results. For example, MICs of isoniazid, ethambutol, and moxifloxacin were determined to be 1.00, 8.00, and 0.25 μg/ml, respectively. IMC, as described here, could be used not just in industrialized countries but also in developing countries because inexpensive and sensitive microcalorimeters are now available.
Purification and partial sequence analysis of pp185, the major cellular substrate of the insulin receptor tyrosine kinase (1991)

Insulin stimulates the tyrosine phosphorylation of a 185-kDa putative cytosolic substrate protein (pp185) in diverse cell types. After intravenous insulin infusion into the live intact rat, pp185 and the 95-kDa insulin receptor beta-subunit were the major proteins that tyrosine phosphorylated in liver, skeletal muscle, and adipose tissue. Both proteins were maximally phosphorylated within 30 s, and both increased in phosphotyrosine content in parallel with increasing insulin dose. However, pp185 tyrosine phosphorylation was transient, with almost complete dephosphorylation within 2-3 min despite continued insulin stimulation. To identify pp185 directly, we purified pp185 from insulin-stimulated rat liver, using a denaturation-based extraction procedure that blocks endogenous protein phosphatases and thus allows a high yield, single step isolation of phosphotyrosyl proteins by anti-phosphotyrosine antibody immunoaffinity absorption. From 50 rat livers, 50-100 pmol of pp185 was isolated. Edman degradation of seven internal tryptic peptide fragments of pp185 yielded novel amino acid sequences, indicating that pp185 is a new protein. Antipeptide antibodies were raised which specifically recognize a single, 185-kDa insulin-stimulated phosphotyrosyl protein in liver, skeletal muscle, adipose tissue, and several cultured cell lines. These results indicate that pp185 is expressed in a variety of insulin-responsive tissues, is the major protein rapidly tyrosine phosphorylated under physiological conditions in the intact animal, and also provide a route for cloning the pp185 gene and elucidating the function of pp185 in insulin signal transduction.
Fc receptors for IgG (Fc gamma Rs) on human monocytes and macrophages are not infectivity receptors for human immunodeficiency virus type 1 (HIV-1): studies using bispecific antibodies to target HIV-1 to various myeloid cell surface molecules, including the Fc gamma R. (1991)

Fc gamma Rs (Fc gamma RI, Fc gamma RII, and Fc gamma RIII) are highly expressed on human mononuclear phagocytes and function in the clearance of immune complexes and opsonized pathogens. We have examined the role of Fc gamma R in mediating antibody-dependent clearance of HIV-1 by human monocytes and monocyte-derived macrophages by using bispecific antibodies (BsAbs) to independently target the virus to Fc gamma RI, Fc gamma RII, or Fc gamma RIII. Virus production was markedly reduced in monocytes cultured with strain HIV-1IIIB opsonized with BsAbs that target the virus to either Fc gamma RI or Fc gamma RII compared to monocytes cultured with virus in the absence of BsAbs or in the presence of BsAbs that target the virus to non-Fc gamma R surface antigens (CD33 and HLA-A,B,C). These results were confirmed using the monotropic isolate HIV-1JRFL. Interaction of HIV-1JRFL with Fc gamma RI or Fc gamma RII on human monocytes and Fc gamma RI, Fc gamma RII, or Fc gamma RIII on monocyte-derived macrophages resulted in markedly reduced levels of virus production in these cultures. Moreover, HIV-1 infection of monocytes and monocyte-derived macrophages was completely blocked by anti-CD4 monoclonal antibodies, indicating that interaction with CD4 is required for infectivity even under conditions of antibody-mediated binding of HIV-1 to Fc gamma R. Thus, we propose that highly opsonized HIV-1 initiates high-affinity multivalent interactions with Fc gamma R that trigger endocytosis and intracellular degradation of the antibody-virus complex. At lower levels of antibody opsonization, there are two few interactions with Fc gamma R to initiate endocytosis and intracellular degradation of the antibody-virus complex, but there are enough interactions to stabilize the virus at the cell surface, allowing antibody-dependent enhancement of HIV-1 infection through high-affinity CD4 interactions. However, our results suggest that interaction of highly opsonized HIV-1 with Fc gamma Rs through BsAbs may reduce viral infectivity through Fc gamma R-mediated cytotoxic mechanisms and, therefore, that BsAbs offer promise as therapeutic reagents in HIV-1 infections.
Relationship between sperm atp content and motility of carp spermatozoa (1995)

Carp spermatozoa are immotile in seminal plasma or in saline solution of high osmolality (> 400 mosmol kg-1). These 'quiescent' spermatozoa initiate a progressive forward motility when transferred in freshwater or in saline solution with low osmolality (< 160 mosmol kg-1). In this study we investigated 'in vitro' the relationship between sperm ATP content (measured by bioluminescence) and sperm motility (analysed by videomicroscopy). Sperm ATP content remained high in the immobilizing medium (200 mM KCl, Tris 30 mM, pH 8.0) where no flagellar movement occurs. Dilution of these spermatozoa in the activating medium (45 mM NaCl, 5 mM KCl, Tris 30 mM, pH 8.0) triggered forward motility which varied with temperature. At 20 degrees C, sperm ATP content decreased rapidly during the progressive forward motility phase from 12 to 4 nmol/10(8) spermatozoa, concomitantly with decreases in velocity (130 to 10 microns s-1) and the beat frequency (50 to 7 Hz). An inhibitor of mitochondrial respiration (KCN 10 mM) produced a drop in sperm ATP content irrespective of the incubation medium (activating or immobilizing). A second phase of sperm motility in the activating medium was induced following a previous transfer of spermatozoa into a medium of high osmolality for a few minutes prior to the second phase. Within 10 minutes, spermatozoa recover 90% of the initial ATP level as well as forward motility. These results suggest that motility of carp spermatozoa depends on sperm ATP synthesized by mitochondrial respiration mainly stored before activation. In low osmolality conditions, the mitochondrial oxidative phosphorylation is unable to compensate for the ATP hydrolysis required to sustain motility.(ABSTRACT TRUNCATED AT 250 WORDS)
Rational strain selection and engineering creates a broad-spectrum, systemically effective oncolytic poxvirus, JX-963 (2007)

Replication-selective oncolytic viruses (virotherapeutics) are being developed as novel cancer therapies with unique mechanisms of action, but limitations in i.v. delivery to tumors and systemic efficacy have highlighted the need for improved agents for this therapeutic class to realize its potential. Here we describe the rational, stepwise design and evaluation of a systemically effective virotherapeutic (JX-963). We first identified a highly potent poxvirus strain that also trafficked efficiently to human tumors after i.v. administration. This strain was then engineered to target cancer cells with activation of the transcription factor E2F and the EGFR pathway by deletion of the thymidine kinase and vaccinia growth factor genes. For induction of tumor-specific cytotoxic T lymphocytes, we further engineered the virus to express human GM-CSF. JX-963 was more potent than the previously used virotherapeutic Onyx-015 adenovirus and as potent as wild-type vaccinia in all cancer cell lines tested. Significant cancer selectivity of JX-963 was demonstrated in vitro in human tumor cell lines, in vivo in tumor-bearing rabbits, and in primary human surgical samples ex vivo. Intravenous administration led to systemic efficacy against both primary carcinomas and widespread organ-based metastases in immunocompetent mice and rabbits. JX-963 therefore holds promise as a rationally designed, targeted virotherapeutic for the systemic treatment of cancer in humans and warrants clinical testing.
Priming does not change promoter sequence requirements for IFN induction or correlate with the expression of IFN regulatory factor-1. (1993)

Pretreatment of L929 cells with IFN enhances Sendai virus-mediated induction of IL-6, TNF-alpha, and IFNA and IFNB genes. The priming effect could be demonstrated at both the RNA and protein levels and the former did not require cellular protein synthesis. Priming increased the Sendai virus-mediated induction of a murine IFNA4 promoter-chloramphenicol acetyltransferase gene hybrid plasmid (A4CAT) in transiently transfected cells, and deletion analysis showed that the identical DNA sequence was required for the inducibility in primed and unprimed cells. Cotransfection of A4CAT plasmid with interferon regulatory factor-1 (IRF-1) expression plasmid increased CAT expression, however, the IRF-1-mediated expression was further enhanced by priming. These results show that the identical inducible element present in the promoter region of IFNA4 gene is required for both the inducibility and the priming effect; however, no direct correlation between the enhancement of expression of the IRF-1 gene and enhancement of expression of IFN, IL-6, and TNF-alpha genes in the primed cells was observed. We suggest that priming facilitates inducer-mediated posttranscriptional modulation of various transcriptional factors that play a role in stimulation of transcription of these genes.
Ex Vivo Cytosolic Delivery of Functional Macromolecules to Immune Cells (2015)

Intracellular delivery of biomolecules, such as proteins and siRNAs, into primary immune cells, especially resting lymphocytes, is a challenge. Here we describe the design and testing of microfluidic intracellular delivery systems that cause temporary membrane disruption by rapid mechanical deformation of human and mouse immune cells. Dextran, antibody and siRNA delivery performance is measured in multiple immune cell types and the approach's potential to engineer cell function is demonstrated in HIV infection studies.
Information authentication using photon-counting double-random-phase encrypted images (2010)

Photon-counting imaging is integrated with optical encryption for information authentication. An image is double-random-phase encrypted, and a photon-limited encrypted image is obtained. The photon-counting encrypted image is generated with few photons and appears sparse; however, we show that it has sufficient information for decryption and authentication. The decrypted image cannot be easily visualized so that an additional layer of information protection is achieved. The authentication is carried out by recognition algorithms. This approach may make the verification process more robust against attacks. To the best of our knowledge, this is the first report on integrating photon-counting imaging and encryption for authentication.
Thrombin stimulates tumor-platelet adhesion in vitro and metastasis in vivo. (1991)

Recent studies have revealed a role for platelets and the platelet-adhesive proteins, fibronectin and von Willebrand factor (vWF) in platelet-tumor cell interaction in vitro and metastasis in vivo. The present report documents the effect of thrombin treatment of platelets on this interaction in vitro and in vivo. In vitro, thrombin at 100-1,000 mU/ml maximally stimulated the adhesion of six different tumor cell lines from three different species two- to fivefold. As little as 1-10 mU/ml was effective. The effect of thrombin was specific (inhibitable by hirudin, dansyl-arginine N-(3-ethyl-1,5 pentanediyl) amide and unreactive with the inactive thrombin analogue N-P-tosyl-L-phenylchloromethylketone-thrombin and D-phenylalanyl-L-propyl-L-arginine chloromethylketone-thrombin (PPACK-thrombin), and required high-affinity thrombin receptors (competition with PPACK-thrombin but not with N-P-tosyl-L-lysine-chloromethyl-ketone-thrombin). Functionally active thrombin was required on the platelet surface. Binding of tumor cells to thrombin-activated platelets was inhibitable by agents known to interfere with the platelet GPIIb-GPIIIa integrin: monoclonal antibody 10E5, tetrapeptide RGDS and gamma chain fibrinogen decapeptide LGGAKQAGDV, as well as polyclonal antibodies against the platelet adhesive ligands, fibronectin and vWF. In vivo, thrombin at 250-500 mU per animal increased murine pulmonary metastases fourfold with CT26 colon carcinoma cells and 68-413-fold with B16 amelanotic melanoma cells. Thus, thrombin amplifies tumor-platelet adhesion in vitro two- to fivefold via occupancy of high-affinity platelet thrombin receptors, and modulation of GPIIb-GPIIIa adhesion via an RGD-dependent mechanism. In vivo, thrombin enhances tumor metastases 4-413-fold with two different tumor cell lines.
Nonsteroidal Progesterone Receptor Ligands. 2. High-Affinity Ligands with Selectivity for Bone Cell Progesterone Receptors (1995)

A novel series of nonsteroidal heterocycles was discovered which display cell-type selective, high-affinity (nanomolar) binding to the progesterone receptors from TE85 osteosarcoma cells but > 1 microM binding affinity to the progesterone receptors from T47D and ZR75 human breast carcinoma cells. Structure-activity relationships were developed for a set of these compounds, and a representative analog 1-(3,4-dichlorobenzoyl)-3-phenyl-1,4,5,6-tetrahydropyridazine++ + (1i, RWJ 25333) was chosen for further evaluation. RWJ 25333 stimulated the in vitro proliferation of human osteoblast-like cells but not human breast cells.
A promising approach for improving the recovery of heart transplants. Prevention of free radical injury through iron chelation by deferoxamine. (1990)

Iron catalysis is involved in the generation of the highly cytotoxic hydroxyl radical and in the chain reactions of subsequent lipid peroxidation that lead to irreversible membrane damage. Assuming that ischemically stored heart transplants may incur free radical injury at the time of reoxygenation, we assessed the effects of the iron chelator deferoxamine in 70 isolated isovolumic buffer-perfused rat hearts subjected to the following protocol: cardioplegic arrest; cold (2 degrees C) storage for 5 hours; global ischemia at 15 degrees C for 1 hour, intended to simulate the implantation procedure; and normothermic reperfusion for 1 additional hour. During poststorage ischemic arrest, the following techniques of myocardial protection were evaluated: hypothermia alone; high-pressure (60 cm H2O) cardioplegia given at 0, 30, and 55 minutes of arrest; low-pressure (30 cm H2O) cardioplegia given at 0 and 55 minutes of arrest; and low-pressure (30 cm H2O) cardioplegia only given at 55 minutes of arrest. Treated hearts had deferoxamine (6 mumol) added to the cardioplegic solution used throughout the experimental time course. Further, in the treated group subjected to the protocol of single cardioplegic delivery at end ischemia, deferoxamine was given both in the cardioplegic reperfusate and in the Krebs buffer over the 15 initial minutes of reflow. Based on comparisons of postreperfusion ventricular pressure development, maximal rate of rise of ventricular pressure, left ventricular compliance, and coronary flow, the best myocardial protection was afforded by deferoxamine given as an additive to single-dose cardioplegic solution at the end of arrest and to the reperfusate during the initial phase of reoxygenation. As the drug has no inotropic effect, its protective action is most likely related to a decrease in catalytic iron available for free radical production and lipid peroxidation. These results support the hypothesis that oxidative damage may contribute to donor heart failure and demonstrate that this form of damage can be efficiently acted upon by iron chelation. The clinical relevance of these data stems from the fact that deferoxamine is available for human use and might become an effective means of improving donor heart preservation in the setting of clinical heart transplantation.
ChemInform Abstract: THE CHEMISTRY OF ALPHA‐FERROCENYLCARBENIUM TETRAFLUOROBORATES PART 2, ELECTROPHILIC REACTIVITY, THERMODYNAMIC AND OPTICAL STABILITY (1975)

Abstract Die Einwirkung von Tetrafluoroborsäure auf die Alkohole (I) liefert die Carbeniumsalze (II), die durch Einwirkung von Nucleophilen wie Cyanidionen oder Aminen in die Derivate (III) übergehen.
111 In Platelet Scintigraphy for the Noninvasive Detection of Carotid Plaque Thrombosis (2001)

Indium-platelet scintigraphy is an accurate noninvasive diagnostic tool to detect thrombotic complications in carotid plaques. Prospective studies should assess its ultimate value in risk stratification, possibly to guide the decision of whether to perform endarterectomy in selected patient categories.
Spreading and migration of human glioma and rat C6 cells on central nervous system myelin in vitro is correlated with tumor malignancy and involves a metalloproteolytic activity. (1998)

Malignant gliomas infiltrate the brain preferentially along myelinated fiber tracts. Central nervous system (CNS) myelin, however, contains inhibitory proteins that block axon regeneration, neurite outgrowth, and cell spreading of astrocytes and fibroblasts. We tested 5 human brain tumor cell lines, 1 rat brain tumor cell line, and 29 short-term cultured specimens from human brain tumors for their ability to spread and migrate on a CNS myelin substrate. Low-grade and pilocytic astrocytoma, ependymoma, medulloblastoma, and meningioma cell lines as well as primary cultures were strongly sensitive to the inhibitory proteins present in the CNS myelin. In contrast, glioblastomas, anaplastic astrocytomas, and oligodendrogliomas were able to spread and migrate on CNS myelin-coated culture dishes, demonstrating that within the gliomas, the ability to overcome the inhibitory effects of the CNS myelin is correlated with the grade of malignancy of the original tumor. Cell spreading of glioblastomas and anaplastic astrocytomas specifically on a CNS myelin substrate was strongly inhibited by the metalloprotease blocker O-phenanthroline and the peptide derivative carbobenzoxy-Phe-Ala-Phe-Tyr-amide, whereas blockers for serine, aspartyl, and cysteine proteases had no effect. Enzymatic peptide degradation assays revealed the presence of a phosphoramidon-sensitive and thiorphan-insensitive metalloproteolytic activity in the plasma membranes of high-grade glioma cells. These results suggest a crucial involvement of a membrane-bound metalloendoprotease in the process of invasive migration of malignant gliomas along CNS white matter fiber tracts.
Application of planar lightwave circuit platformto hybrid integrated optical WDM transmitter/receiver module (1995)

The authors have fabricated an optical WDM module with a simple configuration using a PLC platform together with a spot-size converted LD (SS-LD) and a waveguide PD (WG-PD). Since the module can be formed simply by flip-chip bonding of the SS-LD and the WG-PD, this configuration reduces the number of components, and thus helps achieve a cost reduction.