gebhart/patrepeval huggingface dataset:
Epstein-Barr Virus-Associated Multicentric Leiomyosarcoma in an Adult Patient After Heart Transplantation (2000)

Epstein-Barr virus (EBV)-associated smooth muscle tumors following solid organ transplantation are extremely rare, with only 12 cases reported in the literature thus far. The exact pathogenetic role of EBV infection in the oncogenesis of these soft tissue tumors in immunodeficient patients and the biologic behavior of such tumors is still unclear. We report a 26-year-old man in whom multiple smooth muscle tumors developed 36 to 51 months after heart transplantation. All tumors, two synchronous liver nodules, two subsequently occurring paravertebral tumors, and a single tumor in a vein at the left ankle were surgically resected. The tumor tissue was processed for routine histology and immunohistochemical (IHC) stains. Additionally, competitive polymerase-chain-reaction (PCR), reverse-transcriptase PCR (RT-PCR), as well as in situ hybridization (ISH) were used for EBV particle quantification and gene transcription analysis. The histologic features and immunohistochemical profiles were consistent with leiomyosarcoma in all tumor nodules. EBV infection was detected in >95% of tumor cell nuclei by EBER 1/2 ISH. Competitive PCR revealed 3105 EBV particles per milligram of tumor tissue. The EBV gene expression pattern analyzed by RT-PCR and IHC corresponded to the latency type III with specific expression of EBNA1, EBNA2, LMP1, and LMP2A genes. Under continuous antiviral therapy (famcyclovir) the patient currently shows no evidence of disease. Our data indicate that EBV infection plays a causal role in the development of smooth muscle tumors following organ transplantation. A latency type III, identical to EBV-associated posttransplant lymphoproliferative disorders, was identified and suggests a common pathogenetic mechanism in the development of these histogenetically distinct neoplasms. The fact that the patient currently shows no evidence of disease may be the result of the continuous administration of antiviral therapy because the soft tissue recurrences of the leiomyosarcoma occurred while the patient was not receiving antiviral prophylaxis.
Evidence that activated mucosal T cells play a role in the pathogenesis of enteropathy in human small intestine. (1988)

T cells in explants of human fetal small intestine in organ culture were stimulated in situ with PWM or anti-CD3 antibody to test the hypothesis that activated T cells produce enteropathy in human small intestine. T cell activation was measured by the appearance of CD25+ cells in the lamina propria of the explants and IL-2 production into the organ culture supernatant. We have previously shown that the number of T cells in human fetal gut increased between 14 and 22 wk gestation. Accordingly, after the addition of PWM to cultured explants of fetal intestine the number of CD25+ cells in the lamina propria and the amounts of IL-2 secreted into the organ culture supernatant increased with the age of the explanted tissue. The addition of PWM also produced an age-related enteropathy, most noticeably crypt epithelial cell hyperplasia and villous atrophy, with relatively minor changes in 14-17-wk-old intestine but severe tissue damage in 18-22-wk-old fetal intestine. These enteropathic effects were also produced when mucosal T cells were activated with anti-CD3 mAb. Cyclosporin A completely inhibited the PWM-induced development of CD25+ cells and related tissue damage. These experiments show that activated T cells in human small intestine produce enteropathy. The model provides a new system with which to dissect the mechanisms of T cell-mediated intestinal damage.
Gemcitabine exerts a selective effect on the humoral immune response: implications for combination chemo-immunotherapy. (2002)

Most cytotoxic drugs have gross effects on the immune system, such as neutropenia and lymphopenia. However, their effects on tumor-specific immune responses are unknown. Gemcitabine is a nucleoside analogue that is frequently used to treat non-small cell lung cancer. It is also active in other malignancies, either alone or in combination with cisplatin. Here, we investigate its effects on antigen-specific antitumor immunity using a murine tumor cell line transfected to express influenza virus hemagglutinin (HA). CD4(+), CD8(+), and B220(+) lymphocyte numbers all decreased during chemotherapy (120 microg/g, i.p., every third day for five doses), but B cells were selectively depleted. Gemcitabine induced a profound suppression of the IgG antibody response to HA, and this was unrelated to tumor size. In contrast, in vitro T-lymphocyte recall responses to the class I- and class II-restricted dominant peptide epitopes of HA were enhanced in tumor-bearing, gemcitabine-treated mice. We found that gemcitabine was >2-fold more potent in its ability to inhibit B-lymphocyte proliferation compared with T-lymphocyte proliferation. Thus, gemcitabine does not appear to be detrimental to specific antitumor cellular immunity and may be useful in combination chemo-immunotherapy protocols. In contrast, vaccination protocols requiring a humoral immune response for maximal efficacy may be compromised in patients treated with gemcitabine.
The Past and Present Threat of Rickettsial Diseases to Military Medicine and International Public Health (2002)

Morbidity and mortality caused by rickettsioses have had a major influence on military activities and public health for >2000 years. The threat posed by the rickettsioses is reviewed, focusing on the impact and epidemiology of those that have adversely influenced wartime operations and the current challenges posed by these diseases. With their uneven worldwide distribution, the discovery of drug-refractory strains of Orientia tsutsugamushi, the increased threat of their use in acts of bioterrorism, frequent deployment of troops to regions of endemicity, and exposures due to increased humanitarian missions, these diseases continue to be a threat to military personnel in the field. Effective strategies to reduce the impact of these diseases include development of effective vaccines, enhanced surveillance, and development of new safe, effective, and odorless repellants. The continuation of a proven, highly productive military infectious disease research program is essential for providing solutions to these daunting tasks.
Name Reactions for Functional Group Transformations (2007)

Foreword. Preface. Contributing Authors. Chapter 1. Asymmetric Synthesis. Chapter 2. Reduction. Chapter 3. Oxidation. Chapter 4. Olefination. Chapter 5. Amine Synthesis. Chapter 6. Carboxylic Acid Derivatives Synthesis. Chapter 7. Miscellaneous Functional Group Manipulations. Appendixes. Appendix 1. Table of Contents for Volume 1: Name Reactions in Heterocyclic Chemistry. Appendix 2. Table of Contents for Volume 3: Name Reactions for Chain Extension. Appendix 3. Table of Contents for Volume 4: Name Reactions for Ring Formation. Appendix 4. Table of Contents for Volume 5: Name Reactions in Heterocyclic Chemistry-2. Subject Index.
Insight Into the Kinetic of Amyloid β (1–42) Peptide Self‐Aggregation: Elucidation of Inhibitors’ Mechanism of Action (2007)

The initial transition of amyloid beta (1-42) (Abeta42) soluble monomers/small oligomers from unordered/alpha-helix to a beta-sheet-rich conformation represents a suitable target to design new potent inhibitors and to obtain effective therapeutics for Alzheimer's disease. Under optimized conditions, this reliable and reproducible CD kinetic study showed a three-step sigmoid profile that was characterized by a lag phase (prevailing unordered/alpha-helix conformation), an exponential growth phase (increasing beta-sheet secondary structure) and a plateau phase (prevailing beta-sheet secondary structure). This kinetic analysis brought insight into the inhibitors' mechanism of action. In fact, an increase in the duration of the lag phase can be related to the formation of an inhibitor-Abeta complex, in which the non-amyloidogenic conformation is stabilized. When the exponential rate is affected exclusively, such as in the case of Congo red and tetracycline, then the inhibitor affinity might be higher for the pleated beta-sheet structure. Finally, by adding the inhibitor at the end of the exponential phase, the soluble protofibrils can be disrupted and the Abeta amyloidogenic structure can revert into monomers/small oligomers. Congo red and tetracycline preferentially bind to amyloid in the beta-sheet conformation because both decreased the slope of the exponential growth, even if to a different extent, whereas no effect was observed for tacrine and galantamine. Some very preliminary indications can be derived about the structural requirements for binding to nonamyloidogenic or beta-sheet amyloid secondary structure for the development of potent antiaggregating agents. On these premises, memoquin, a multifunctional molecule that was designed to become a drug candidate for the treatment of Alzheimer's disease, was investigated under the reported circular dichroism assay and its anti-amyloidogenic mechanism of action was elucidated.
Circumventing the Crabtree Effect: Replacing Media Glucose with Galactose Increases Susceptibility of HepG2 Cells to Mitochondrial Toxicants (2007)

Many highly proliferative cells generate almost all ATP via glycolysis despite abundant O(2) and a normal complement of fully functional mitochondria, a circumstance known as the Crabtree effect. Such anaerobically poised cells are resistant to xenobiotics that impair mitochondrial function, such as the inhibitors rotenone, antimycin, oligomycin, and compounds like carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone (FCCP), that uncouple the respiratory electron transfer system from phosphorylation. These cells are also resistant to the toxicity of many drugs whose deleterious side effect profiles are either caused, or exacerbated, by impairment of mitochondrial function. Drug-induced mitochondrial toxicity is shown by members of important drug classes, including the thiazolidinediones, statins, fibrates, antivirals, antibiotics, and anticancer agents. To increase detection of drug-induced mitochondrial effects in a preclinical cell-based assay, HepG2 cells were forced to rely on mitochondrial oxidative phosphorylation rather than glycolysis by substituting galactose for glucose in the growth media. Oxygen consumption doubles in galactose-grown HepG2 cells and their susceptibility to canonical mitochondrial toxicants correspondingly increases. Similarly, toxicity of several drugs with known mitochondrial liabilities is more readily apparent in aerobically poised HepG2 cells compared to glucose-grown cells. Some drugs were equally toxic to both glucose- and galactose-grown cells, suggesting that mitochondrial impairment is likely secondary to other cytotoxic mechanisms.
Efficient Route toC2Symmetric Heterocyclic Backbone Modified Cyclic Peptides (2005)

[reaction: see text] A tandem dimerization-macrocyclization approach using 1,3-dipolar azide-alkyne cycloaddition reactions has been employed in the facile and convergent solution phase syntheses of C2 symmetric cyclic peptide scaffolds bearing triazole epsilon2-amino acids as dipeptide surrogates.
Monoclonal antibody-mediated enhancement of dengue virus infectionin vitroandin vivoand strategies for prevention (2007)

Infection with dengue virus (DENV) or any other flavivirus induces cross-reactive, but weakly neutralizing or nonneutralizing, antibodies that recognize epitopes involving the fusion peptide in the envelope glycoprotein. Humanized mAb IgG 1A5, derived from a chimpanzee, shares properties of cross-reactive antibodies. mAb IgG 1A5 up-regulated DENV infection by a mechanism of antibody-dependent enhancement (ADE) in a variety of Fc receptor-bearing cells in vitro. A 10- to 1,000-fold increase of viral yield in K562 cells, dependent on the DENV serotype, was observed over a range of subneutralizing concentrations of IgG 1A5. A significant increase of DENV-4 viremia titers (up to 100-fold) was also demonstrated in juvenile rhesus monkeys immunized with passively transferred dilutions of IgG 1A5. These results, together with earlier findings of ADE of DENV-2 infection by a polyclonal serum, establish the primate model for analysis of ADE. Considering the abundance of these cross-reactive antibodies, our observations confirm that significant viral amplification could occur during DENV infections in humans with prior infection or with maternally transferred immunity, possibly leading to severe dengue. Strategies to eliminate ADE were explored by altering the antibody Fc structures responsible for binding to Fc receptors. IgG 1A5 variants, containing amino acid substitutions from the Fc region of IgG2 or IgG4 antibodies, reduced but did not eliminate DENV-4-enhancing activity in K562 cells. Importantly, a 9-aa deletion at the N terminus of the CH(2) domain in the Fc region abrogated the enhancing activity.
Molecular Characterization of Neuroendocrine Prostate Cancer and Identification of New Drug Targets (2011)

We report on the largest in-depth molecular analysis of NEPC and provide new insight into molecular events involved in the progression of prostate cancer.
An Epidemic, Toxin Gene–Variant Strain of Clostridium difficile (2005)

A previously uncommon strain of C. difficile with variations in toxin genes has become more resistant to fluoroquinolones and has emerged as a cause of geographically dispersed outbreaks of C. difficile-associated disease.
Hormonal Regulation of an Islet-Specific Enhancer in the Pancreatic Homeobox Gene STF-1 (1997)

The homeobox protein STF-1 appears to function as a master control switch for expression of the pancreatic program during development. Here we characterize a composite enhancer which directs STF-1 expression to pancreatic islet cells via two functional elements that recognize the nuclear factors HNF-3beta and BETA-2. In keeping with their inhibitory effects on islet cell maturation, glucocorticoids were found to repress STF-1 gene expression by interfering with HNF-3beta activity on the islet-specific enhancer. Overexpression of HNF-3beta suppressed glucocorticoid receptor-mediated inhibition of the STF-1 gene, and our results suggest that the expansion of pancreatic islet precursor cells during development may be restricted by hormonal cues which regulate STF-1 gene expression.
Electron mobility enhancement in epitaxial multilayer Si-Si1−xGex alloy films on (100) Si (1982)

Enhanced Hall-effect mobilities have been measured in epitaxial (100)-oriented multilayer n-type Si/Si1−xGex films grown on single-crystal Si substrates by chemical vapor deposition. Mobilities from ∼20 to 40% higher than that of epitaxial Si layers and ∼100% higher than that of epitaxial SiGe layers on Si were measured for the doping range ∼8×1015–∼1017 cm−3. The mobilities of multilayer Si/SiGe films approach that of single-crystal Si films at ∼2×1017 cm−3. No mobility enhancement was observed in multilayer p-type (100) films and n-type (111)-oriented films. Experimental studies included the effects upon film properties of layer composition, total film thickness, doping concentrations, layer thicknesses, and growth temperature.
STUDIES ON ANTIBODY PRODUCTION (1955)

A method for the specific histochemical demonstration of antibody in cells and parts of cells is described. It consists of carrying out a two stage immunological reaction on frozen sections of tissues: (a) allowing reaction between antibody in the tissue and dilute antigen applied in vitro, and (b) the detection of those areas where this antigen has been specifically absorbed by means of a precipitin reaction carried out with fluorescein-labelled antibody. Examination under the fluorescence microscope reveals the yellow-green fluorescence of fluorescein over those areas where a precipitate has formed. A study of the hyperimmune rabbit on the first few days after the last of a series of intravenous antigen injections reveals that antibody against human gamma-globulin or ovalbumin is present in groups of plasma cells in the red pulp of the spleen, the medullary areas of lymph nodes, the submucosa of the ileum, and the portal connective tissue of the liver. Because of extensive non-specific reactions, the bone marrow could not be examined. Small amounts of antibody were occasionally visible in cells in the lymphoid follicles of the spleen and lymph nodes, so that a minor contribution by lymphocytes to antibody synthesis cannot be excluded.
Synthesis and properties of a series of sterically hindered guanidine bases (1982)

By the reaction of Vilsmeier salts, derived from tetra-alkylureas or from tetra-alkylthioureas, with primary aliphatic amines, a series of sterically hindered penta-alkyl guanidines has been prepared. 2-t-Butyl-1′,1′,3″,3″-tetramethylguanidine and pentaisopropylguanidine combine ease of preparation with a range of resistance to alkylating agents. Preliminary experiments indicate that these inexpensive bases will be useful in organic synthesis.
Cloning and Expression of Rat cDNA Encoding Corticosteroid 11β-Dehydrogenase (1989)

Corticosteroid 11 beta-dehydrogenase (11-DH) catalyzes the conversion of cortisol to the inactive metabolite cortisone. Absence of 11-DH activity leads to a potentially fatal form of childhood hypertension termed apparent mineralocorticoid excess. As a first step in elucidating the molecular basis of this disorder, we isolated and characterized a rat cDNA clone encoding 11-DH. This clone hybridized to a single mRNA species in liver, kidney, and testis RNA but not to RNA from heart. The insert was 1265 base pairs long and included an 861-base pair open reading frame encoding 287 amino acids. A search of sequence databases revealed that 11-DH is identical in about 27% of amino acid residues to ribitol dehydrogenase from Klebsiella and to the product of the nodG gene from the nitrogen-fixing bacterium, Rhizobium meliloti, thus defining a new superfamily of genes encoding dehydrogenases. The 11-DH cDNA was expressed by transfection into Chinese hamster ovary cells under the control of an SV40 promoter. The expressed enzyme mediated both 11 beta-dehydrogenation and the reverse 11-oxoreduction reaction. Southern blot analysis of rat and human DNA suggested that additional genes related to 11-DH exist in both species.
Studies on psychotropic agents. VI. Synthesis of 1'-methylspiro[6-fluoroindan-1,3'-pyrrolidine]-3-one and related compounds. (1980)

The title compounds (19) were synthesized by rearrangement of the 1-ethoxycarbonyl-4-aryl-3, 4-epoxypiperidines (7) to give the 3-aryl-3-formylpyrrolidine derivatives (12) for pharmacological testing. Compound (19b) exhibited moderate central nervous system depressing activity. The mechanism of the rearrangement of 1-substituted 4-aryl-3, 4-epoxypiperidine with boron trifluoride etherate is discussed.
Protocol for Analyzing Human Leukocyte Antigen Variants and Sexually Transmitted Infections: From Genotyping to Immunoassays (2012)

This chapter describes experimental and analytical procedures that can be used to decipher the specific role of human leukocyte antigen (HLA) variants in infectious diseases. The techniques are distilled from more than one decade of active immunogenetics research, primarily on sexually transmitted infections (STIs) caused by viral and bacterial pathogens, including human immunodeficiency virus type 1 (HIV-1), hepatitis B virus (HBV), and Chlamydia trachomatis. The specific approaches cover (1) sequence-specific oligonucleotide (SSO) probe hybridization for low-resolution genotyping, (2) sequencing-based typing (SBT) for high-resolution, (3) statistical methods for testing associations between HLA variants and phenotypic traits, and (4) enzyme-linked immunospot (ELISpot) assay for enumerating HLA-restricted and epitope-specific T-lymphocyte responses. Proper application of these mature and robust techniques should help establish the importance of individual HLA alleles, haplotypes, and supertypes to host-pathogen interactions.
Fuzzy metaqueries for guiding the discovery process in KDD (2002)

This paper introduces the concept of fuzzy metaqueries and describes a framework for knowledge discovery in database (KDD) that has fuzzy metaqueries as its base. Fuzzy metaqueries are second order like fuzzy rules, very useful for the integration of inductive learning, deductive verification, human intuition and uncertainty handling.
TRANSPLANTED ACELLULAR ALLOGRAFT DERMAL MATRIX (1995)

The use of allograft donor skin as a permanent skin transplant in full-thickness burns is limited by its immunogenic properties and by the inappropriateness of immunosuppression of a burn patient. Allograft skin will initially take on a full-thickness wound, but it is ultimately rejected. This immunogenic response to allograft skin is directed primarily against the cells of the epidermis and the endothelial cells in the dermis. To date, it has not been possible to remove these immunogenic cells while maintaining the integrity of the nonimmunogenic components of allograft dermis. In this study, we have investigated a method of processing porcine skin to produce an acellular, structurally intact, dermal matrix. We have developed a process that de-epidermizes and decellularizes fresh porcine skin, while maintaining the basement membrane complex and the extracellular matrix structure of the dermis. Porcine dermis processed by this method was initially assessed for toxicity in a rat subcutaneous implant study. In vivo assessment confirmed the absence of local and systemic toxicity. Subsequently, we investigated the potential use of this matrix in combination with a meshed split-thickness autograft (STSG) as a permanent allograft in full-thickness wounds in pigs. Histological analysis revealed that the dermal matrix supported fibroblast infiltration, neovascularization, and keratinocyte migration from an overlying STSG. There was no evidence of an inflammatory cell infiltrate or a cell-mediated immune response. This apparent lack of an immune response was also tested in vitro by assessing recipient lymphocyte proliferation in response to an extract of the dermal matrix. These results suggest that skin processed by this method has the potential to be used as a permanent dermal allograft to augment the performance of an STSG in the closure of full-thickness wounds.
Analysis of Listeria monocytogenes antigens with monoclonal antibodies. (1984)

Hybridomas secreting antibodies directed against Listeria monocytogenes were produced by the fusion of a drug sensitive tumor cell line with splenic B cells from mice immunized with L. monocytogenes. A solid phase radioimmunoassay (RIA) screening procedure was performed with three forms of listerial antigens: (i) heat killed L. monocytogenes (HKLM); (ii) isopycnic gradient purified soluble listerial proteins (SLP) and (iii) syngeneic macrophages which had ingested HKLM (MAC-LM). Ninety-three hybridoma lines were identified which showed antibody reactivity to at least one of the antigenic forms. The predominant isotypes of hybridoma derived antibodies were IgG2 and IgM. Of those antibodies reactive with HKLM 70% appeared species specific and did not react with L. grayi, L. denitrificans or L. murrayi. The others (30%) showed several cross-reactivity patterns with bacteria such as Staphylococcus aureus, Escherichia coli, and Bacillus subtilis. Interestingly, of those positive on MAC-LM (27), 13 lines were reactive only with HKLM, 8 with all three antigenic forms, and 6 were reactive only with MAC-LM. Three lines were also identified which reacted with SLP alone. We anticipate that these antibody reagents will prove extremely useful in the identification and purification of antigenic structures and in the study of macrophage functions relating to antigen processing and presentation.