gebhart/patrepeval huggingface dataset:
Simultaneous Treatment of Human Bronchial Epithelial Cells with Serine and Cysteine Protease Inhibitors Prevents Severe Acute Respiratory Syndrome Coronavirus Entry (2012)

The type II transmembrane protease TMPRSS2 activates the spike (S) protein of severe acute respiratory syndrome coronavirus (SARS-CoV) on the cell surface following receptor binding during viral entry into cells. In the absence of TMPRSS2, SARS-CoV achieves cell entry via an endosomal pathway in which cathepsin L may play an important role, i.e., the activation of spike protein fusogenicity. This study shows that a commercial serine protease inhibitor (camostat) partially blocked infection by SARS-CoV and human coronavirus NL63 (HCoV-NL63) in HeLa cells expressing the receptor angiotensin-converting enzyme 2 (ACE2) and TMPRSS2. Simultaneous treatment of the cells with camostat and EST [(23,25)trans-epoxysuccinyl-L-leucylamindo-3-methylbutane ethyl ester], a cathepsin inhibitor, efficiently prevented both cell entry and the multistep growth of SARS-CoV in human Calu-3 airway epithelial cells. This efficient inhibition could be attributed to the dual blockade of entry from the cell surface and through the endosomal pathway. These observations suggest camostat as a candidate antiviral drug to prevent or depress TMPRSS2-dependent infection by SARS-CoV.
Allogeneic mesenchymal stem cell treatment alleviates experimental and clinical Sjögren syndrome (2012)

Sjögren syndrome (SS) is a systemic autoimmune disease characterized by dry mouth and eyes, and the cellular and molecular mechanisms for its pathogenesis are complex. Here we reveal, for the first time, that bone marrow mesenchymal stem cells in SS-like NOD/Ltj mice and human patients were defective in immunoregulatory functions. Importantly, treatment with mesenchymal stem cells (MSCs) suppressed autoimmunity and restored salivary gland secretory function in both mouse models and SS patients. MSC treatment directed T cells toward Treg and Th2, while suppressing Th17 and Tfh responses, and alleviated disease symptoms. Infused MSCs migrated toward the inflammatory regions in a stromal cell-derived factor-1-dependent manner, as neutralization of stromal cell-derived factor-1 ligand CXCR4 abolished the effectiveness of bone marrow mesenchymal stem cell treatment. Collectively, our study suggests that immunologic regulatory functions of MSCs play an important role in SS pathogenesis, and allogeneic MSC treatment may provide a novel, effective, and safe therapy for patients with SS.
Recent Theoretical Developments (1997)

In the 1930s criminology was the subject of a scathing critique by Michael and Adler (1933) (see Chapter 7). Half a century later, Albert Reiss Jr. (1981b:3) reminded criminologists that: The body of knowledge that we think of as criminology owes more to models and theories from psychology and sociology than from any other discipline. Criminology, to be sure, has not lent itself to any single theoretical formulation within those disciplines, though there have been fashions in theories of crime.
Disulfide linkage of biotin identifies a 106-kDa Ca2+ release channel in sarcoplasmic reticulum (1989)

Reactive disulfide reagents (RDSs) with a biotin moiety have been synthesized and found to cause Ca2+ release from sarcoplasmic reticulum (SR) vesicles. The RDSs oxidize SH sites on SR proteins via a thiol-disulfide exchange, with the formation of mixed disulfide bonds between SR proteins and biotin. Biotinylated RDSs identified a 106-kDa protein which was purified by biotin-avidin chromatography. Disulfide reducing agents, like dithiothreitol, reverse the effect of RDSs and thus promoted active re-uptake of Ca2+ and dissociated biotin from the labeled protein indicating that biotin was covalently linked to the 106-kDa protein via a disulfide bond. Several lines of evidence indicate that this protein is not Ca2+, Mg2+-ATPase and is not a proteolytic fragment or a subunit of the 400-kDa Ca2+-ryanodine receptor complex (RRC). Monoclonal antibodies against the ATPase did not cross-react with the 106-kDa protein, and polyclonal antibodies against the 106-kDa did not cross-react with either the ATPase or the 400-kDa RRC. RDSs did not label the 400-kDa RRC with biotin. Linear sucrose gradients used to purify the RRC show that the 106-kDa protein migrated throughout 5-20% linear sucrose gradients, including the high sucrose density protein fractions containing 400-kDa RRC. Protease inhibitors diisopropylfluorophosphate used to prevent proteolysis of 400-kDa proteins did not alter the migration of 106-kDa in sucrose gradients nor the patterns of biotin labeling of the 106-kDa protein. Incorporation of highly purified 106-kDa protein (free of RRC) in planar bilayers revealed cationic channels with large Na+ (gNa+ = 375 +/- 15 pS) and Ca2+ (gCa2+ = 107.7 +/- 12 pS) conductances which were activated by micromolar [Ca2+]free or millimolar [ATP] and blocked by micromolar ruthenium red or millimolar [Mg2+]. Thus, the SR contains a sulfhydryl-activated 106-kDa Ca2+ channel with apparently similar characteristics to the 400-kDa "feet" proteins.
Pain Perception following Subcutaneous Injections of Citrate-Buffered and Phosphate-Buffered Epoetin Alpha (1998)

Subcutaneous injection of citrate-buffered epoetin alpha (EPO-alpha) causes pain. Substitution of citrate buffer with a phosphate buffer in the EPO-alpha resulted in a significant reduction in duration and severity of pain. It is possible that sodium citrate which is present in the EPO-alpha may be the agent that causes discomfort in the patients.
A Graphics Image Processing System (2008)

Patent document images maintained by the U.S. patent database have a specific format, in which figures and text descriptions are separated into different sections. This makes it difficult for users to refer to a figure while reading the description or vice versa. The system introduced in this paper is to prepare these patent images for a friendly user browsing interface. The system is able to extract captions and labels from figures. After obtaining captions and labels, figures and the relevant descriptions are linked together. Hence, users are able to easily find the relevant figure by clicking captions or labels in the description, or vice versa.
Activation of MHC Class I, II, and CD40 Gene Expression by Histone Deacetylase Inhibitors (2000)

Epigenetic mechanisms are involved in regulating chromatin structure and gene expression through repression. In this study, we show that histone deacetylase inhibitors (DAIs) that alter the acetylation of histones in chromatin enhance the expression of several genes on tumor cells including: MHC class I, II, and the costimulatory molecule CD40. Enhanced transcription results in a significant increase in protein expression on the tumor cell surface, and expression can be elicited on some tumors that are unresponsive to IFN-gamma. The magnitude of induction of these genes cannot be explained by the effect of DAIs on the cell cycle or enhanced apoptosis. Induction of class II genes by DAIs was accompanied by activation of a repressed class II transactivator gene in a plasma cell tumor but, in several other tumor cell lines, class II was induced in the apparent absence of class II transactivator transcripts. These findings also suggest that the abnormalities observed in some tumors in the expression of genes critical to tumor immunity may result from epigenetic alterations in chromatin and gene regulation in addition to well-established mutational mechanisms.
Wide area gigabit access network based on 12.5GHz spaced 256 channel super-dense WDM technologies (2001)

The authors propose a novel wide area access ring network utilising super-dense WDM technologies that offer 256 12.5 GHz spaced optical wavelengths. A multi-optical carrier generation scheme from one optical source is employed to reduce the optical transmitter cost. This network can cost-effectively provide gigabit access services.
Adrenergics and Adrenergic‐Blocking Agents (2003)

Abstract This chapter reviews the drugs currently available in the United States that exert their therapeutic effects through actions on α‐ and β‐adrenoceptors and biosynthesis, release, and processing of the neurotransmitter norepinephrine. Included in the review are drugs acting as selective and nonselective agonists and antagonists at both α‐ and β‐adrenoceptors, as well as drugs that interfere with norepinephrine biosynthesis and release. Therapeutic categories include antihypertensives, bronchodilators, antiglaucoma agents, vasopressors, and nasal decongestants. Structure‐activity relationships are reviewed as are the structure and function of various adrenoceptors. Briefly covered is the metabolism of representative drugs in each structural class as well as recent developments in approaches to new drugs in the areas of selective α 1A ‐antagonists for treatment of prostatic hypertrophy and selective β 3 ‐agonists for treatment of obesity and diabetes.
Effective Postexposure Treatment of Retrovirus-Induced Disease with Immunostimulatory DNA Containing CpG Motifs (2002)

Therapeutic strategies for the treatment of acute retroviral infections have relied mainly on antiviral drugs. In this study we used the Friend virus model system to demonstrate that enhancement of the immune system can also have dramatic therapeutic effects. Since resistance to Friend virus-induced leukemia in mice is associated with T helper cell type 1 (Th1) immune responses, we enhanced these responses in susceptible mice by treatment with synthetic oligodeoxynucleotides containing unmethylated CpG motifs (CpG-ODN). Treatments begun at 4 days postinfection increased recovery from 6% in the control group to 74% in the CpG-treated group. CpG-mediated recovery was associated with a significant reduction of viral loads in the blood and spleens of treated mice compared to those of control animals. The treatment promoted Th1-type cytokine production by splenocytes of Friend virus-infected mice and augmented Friend virus-specific cytotoxic T-cell responses, but no influence on the virus-specific neutralizing antibody response was observed. Friend virus-specific CD8(+) T cells were critical for effective treatment with CpG-ODN, since in vivo depletion of these cells from treated mice prevented their recovery. Our results demonstrate that CpG-ODN therapy can significantly enhance virus-specific cellular immune responses and prevent retrovirus-induced disease. These findings may have implications for antiviral therapy in general.
Incorporation of perforated and demineralized cortical bone allografts. Part I: radiographic and histologic evaluation. (2001)

Laser perforated and partially demineralized cortical bone allografts were orthotopically transplanted into sheep tibiae. This paper reports results of the mechanical testing of the transplanted bones, which was done at nine months postoperatively. Animals were divided into three groups of eight according to the type of cortical allograft used: group 1, no treatment; group 2, laser hole grid; and group 3, laser hole grid and partial demineralization. Thus, changes in flexural rigidity of 24 transplanted whole tibiae were investigated. Starting in the anterior direction at the tibial tuberosity, the flexural rigidity was determined using a nondestructive 4-point bending test. The elliptical distribution of the flexural rigidity was compared to the untreated contralateral control bone of each animal. Mechanical parameters were defined as percentage rates for comparative analysis between groups. Flexural rigidity measurement showed that bones transplanted with untreated allografts were stiffer than contralateral control bones. Partial demineralization of allografts reduced the flexural rigidity of transplanted bones below the level of contralateral control bones. Flexural rigidities of test bones transplanted with laser perforated and partially demineralized allografts were higher than those seen in bones transplanted with partially demineralized allografts. These results were corroborated by the histologic analysis which showed that untreated allografts, although surrounded by a periosteal bone cuff that effectively increased their outer diameter. In contrast, excessive bone resorption was observed in partially demineralized allografts. Laser-perforated and partially demineralized allografts showed histologic evidence of complete incorporation into the host bone. Based on this mechanical evaluation, it was concluded that processing of cortical bone allografts by the combination of perforation and partial demineralization resulted in improved mechanical strength of the transplanted bones as compared to processing by partial demineralization alone.
Patient self‐injection: a new approach to administering luteinizing hormone‐releasing hormone analogues (2000)

This pilot study of 20 patients showed that it is feasible for a selected group of patients to be taught self-injection of an LHRH analogue, and that some patients prefer this mode of drug administration.
Lysine 43 Is Trimethylated in Subunit c from Bovine Mitochondrial ATP Synthase and in Storage Bodies Associated with Batten Disease (2004)

The hydrophobic membrane protein, subunit c, has been isolated from ATP synthase purified from bovine heart mitochondria. It has also been obtained from lysosomal storage bodies associated with ceroid lipofuscinosis from ovine liver and from human brain tissue of a victim of Batten disease. It is likely that the lysosomal protein has originated from the mitochondrion. These samples have been characterized by mass spectrometric methods. Irrespective of its source, subunit c has an intact molecular mass of 7650 Da, 42 Da greater than the value calculated from the amino acid sequence, and the protein has been modified post-translationally. In all three samples, the modification is associated with lysine 43, which lies in a polar loop region linking the two transmembrane alpha-helices of the protein. This residue is conserved throughout vertebrate sequences. The additional mass arises from trimethylation and not acetylation at the epsilon-N-position of the residue. These experiments show that the post-translational modification of subunit c is not, as has been suggested, an abnormal phenomenon associated with the etiology of Batten disease and ceroid lipofucinoses. Evidently, it occurs either before or during import of the protein into mitochondria or at a mitochondrial location after completion of the import process. The function of the trimethyllysine residue in the assembled ATP synthase complex is obscure. The residue and the modification are not conserved in all ATP synthases, and their role in the assembly and (or) functioning of the enzyme appear to be confined to higher organisms.
Clonal analysis of human cytotoxic T lymphocytes: T4+ and T8+ effector T cells recognize products of different major histocompatibility complex regions. (1982)

Alloreactive human T lymphocytes were cloned in soft agar or by limiting dilution and subsequently propagated with interleukin 2 and alloantigen for 8 months or more. By indirect immunofluorescence every clone was reactive with anti-Ia antibodies as well as the T cell-specific antibodies anti-T3 and anti-T11 and expressed either T4 or T8 antigens. All 15T8+ clones were highly cytotoxic for the sensitizing alloantigen. In contrast, only two of seven T4+ clones mediated cytotoxic effector function. The specificity of T4+ and T8+ clones and subclones was analyzed on a panel of typing cells and by antibody blocking studies of major histocompatibility complex (MHC) determinants on the stimulating alloantigen. It was found that T8+ clones killed targets that shared class I MHC antigens (HLA-A,B) with the original stimulator cells whereas cytotoxic T4+ clones were directed at class II MHC antigens (Ia-related). Preincubation of the allogeneic target cell with a monoclonal antibody to a nonpolymorphic HLA alpha-chain determinant inhibited killing by the T8+ clones but did not affect T4+ cytotoxic function. In a reciprocal fashion, anti-IA antibodies to common framework structures on the same target cell blocked killing by T4+ but not by T8+ clones. These results indicate that T4+ and T8+ T lymphocytes have receptors for different classes of MHC antigens and suggest tha cytotoxic T4+ subpopulations might be important in human transplantation and autoimmune disorders.
Addition and cycloaddition reactions of furo[3,2-b]pyrroles and their benzo[b] analogues: An NMR study of structure of products (1988)

Reaction of furo[3,2- b ]pyrroles and their benzo[ b ] analogues with dimethyl butynedioate and ethyl propyonate were investigated. The reaction course is influenced by substituents on the system. Products of [4 + 2] cycloaddition to the furan or pyrrole nucleus as well as products of Michael addition to the benzo[ b ]furo[3,2- b ]pyrrole system have been found. The structure of the products has been proven by 1 H NMR and 13 C NMR spectroscopy.
Egg membrane as a new biological dressing in split-thickness skin graft donor sites: a preliminary clinical evaluation. (2003)

From this preliminary study, egg membrane may be an ideal STSG donor site dressing, as it possesses properties of pain relief, wound protection, promotion of healing, and low cost. However, the limited unit size must be overcome, and its clinical application for burn wounds should be studied.
Specific interaction of human Tamm-Horsfall gylcoprotein with leucoagglutinin, a lectin from Phaseolus vulgaris (red kidney bean) (1979)

Human Tamm-Horsfall glycoprotein inhibits lymphocyte transformation induced by leucoagglutinin and haemagglutinin from Phaseolus vulgaris (red kidney bean). The glycoprotein interacts with the two lectins, giving insoluble precipitates. The interaction with leucoagglutinin is highly specific, and the shape of the precipitin curve is that of an antigen-antibody reaction; precipitation is specifically inhibited by N-acetyl-D-galactosamine. Results are discussed, and it is suggested that inhibition of lymphocyte transformation is due to competition between human Tamm-Horsfall glycoprotein and carbohydrate receptors on lymphocytes for the two lectins. The interaction between human Tamm-Horsfall glycoprotein and Phaseolus vulgaris lectins has been used to develop a one-step procedure for the separation of the two lectins by affinity chromatography on (human Tamm-Horsfall-glycoprotein)-Sepharose.
Leukocyte-endothelial interactions and organ injury: the role of adhesion molecules. (1994)

Polymorphonuclear neutrophils (PMN) play an important role in host defense and immune surveillance. However, PMNs can be detrimental when inflammatory stimuli are excessive and can lead to uncontrolled PMN adherence to microvascular endothelium, resulting in tissue and organ injury in the critically ill. The molecular basis of PMN-endothelial adherence is dependent on two groups of adhesion molecules and their co-specific ligands: the beta 2 integrins and their counterstructures, which are members of the immunoglobulin gene superfamily; and the selectins and their carbohydrate ligands expressed on vascular mucins and other glycoproteins or glycolipids. This review characterizes the events leading to PMN-endothelial adhesion and examines a number of in vivo models in which adhesion molecule blockade has protected against injury. The role of adhesion molecules in T-lymphocyte adhesion and immune surveillance of transplant allografts is also briefly discussed. The infectious risks of adhesion molecule blockade are reviewed.
Expression of Transforming Growth Factor-β in the Rat Ventral Prostate during Castration-Induced Programmed Cell Death (1989)

Castration-induced androgen deprivation leads to the activation of the programmed death of the androgen-dependent prostatic epithelial cells in the rat ventral prostate. In order to identify potential mediators of this programmed cell death, the expression of transforming growth factor-beta (TGF beta) in the rat ventral prostate was studied, after castration induced-androgen withdrawal. Steady state levels of TGF beta mRNA were determined by Northern blot analysis and compared with mRNA levels for prostatein C3, the major androgen-dependent secretory protein of ventral prostate and also with mRNA levels for TRPM-2, a gene that is specifically expressed during castration induced prostatic cell death. Within the first day after castration there was a dramatic increase in the levels of TGF beta mRNA in the ventral prostate (approximately 10-fold) and by 4 days after castration TGF beta mRNA was maximally expressed (approximately 40-fold increase), by which time the androgen-dependent C3 secretory protein mRNA transcripts have diminished to undetectable levels. Androgen administration to 4-day castrated rats led to a marked decrease in TGF beta mRNA to a level comparable to its constitutive expression obtained in the intact control animals, indicating that expression of TGF beta in the rat ventral prostate is under negative androgenic regulation. The transcript levels encoding TRPM-2 initially increased 10-fold within the first day after castration and by day 4 post castration there was a dramatic increase (approximately 50-fold) which correlated well with the maximal rate of cell death of the androgen-dependent prostatic epithelial cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Matrix metalloproteinase inhibitor BB-94 (batimastat) inhibits human colon tumor growth and spread in a patient-like orthotopic model in nude mice. (1994)

Matrix metalloproteinases have been implicated in the growth and spread of metastatic tumors. This role was investigated in an orthotopic transplant model of human colon cancer in nude mice using the matrix metalloproteinase inhibitor BB-94 (batimastat). Fragments of human colon carcinoma (1-1.5 mm) were surgically implanted orthotopically on the colon in 40 athymic nu/nu mice. Administration of BB-94 or vehicle (phosphate buffered saline, pH 7.4, containing 0.01% Tween 80) commenced 7 days after tumor implantation (20 animals/group). Animals received 30 mg/kg BB-94 i.p. once daily for the first 60 days and then 3 times weekly. Treatment with BB-94 caused a reduction in the median weight of the primary tumor from 293 mg in the control group to 144 mg in the BB-94 treated group (P < 0.001). BB-94 treatment also reduced the incidence of local and regional invasion, from 12 of 18 mice in the control group (67%) to 7 of 20 mice in the treated group (35%). Six mice in the control group were also found to have metastases in the liver, lung, peritoneum, abdominal wall, or local lymph nodes. Only two mice in the BB-94 group had evidence of metastatic disease, in both cases confined to the abdominal wall. The reduction in tumor progression observed in the BB-94-treated group translated into an improvement in the survival of this group, from a median survival time of 110 days in the control group to a median survival time of 140 days in the treated group (P < 0.01). Treatment with BB-94 was not associated with any obvious toxic effect, and these results suggest that such agents may be effective as adjunctive cancer therapies.