gebhart/patrepeval huggingface dataset:
Prevention of acute graft-versus-host disease by treatment with a novel immunosuppressant. Cholera toxin B subunit. (1995)

Transplantation of allogeneic bone marrow (BM) is often complicated by the development of acute graft-vs-host disease (GVHD) caused by contaminating T cells in BM inocula because of activation of the host reactive T effector cells. Using a murine model for acute GVHD caused by injection of parental C57Bl/6 splenocytes into unirradiated (C57Bl/6 x DBA/2) F1 hybrids, we demonstrated that pretreatment of the inocula with a novel immunosuppressant, B subunit of cholera toxin (CT-B) impaired the ability of C57Bl/6 T cells to induce acute GVHD in F1 recipients. F1 mice injected with CT-B-treated C57Bl/6 splenocytes did not develop significant splenomegaly, and no antihost CTLs were found in their spleens. Moreover, these mice did not suffer from aplastic anemia, nor from general immunosuppression. Immunofluorescence studies suggest that treatment of the inducing inocula with CT-B selectively prevents accumulation of the host-reactive CD8+ T cells in F1 mice. Furthermore, our experiments demonstrated that CT-B treatment does not impair the ability of BM progenitors to form colonies in semisolid culture or in lethally irradiated hosts. Thus, taken together, our data suggest that ex vivo CT-B treatment can be used in allogeneic BM transplantation to prevent acute GVHD.
Incidence and risk factors for Progressive Multifocal Leukoencephalopathy among patients with selected rheumatic diseases (2011)

PML occurs at a very low incidence among patients with rheumatic diseases but can occur even in the absence of HIV or malignancy.
Contribution of central neuroplasticity to pathological pain: review of clinical and experimental evidence (1993)

Peripheral tissue damage or nerve injury often leads to pathological pain processes, such as spontaneous pain, hyperalgesia and allodynia, that persist for years or decades after all possible tissue healing has occurred. Although peripheral neural mechanisms, such as nociceptor sensitization and neuroma formation, contribute to these pathological pain processes, recent evidence indicates that changes in central neural function may also play a significant role. In this review, we examine the clinical and experimental evidence which points to a contribution of central neural plasticity to the development of pathological pain. We also assess the physiological, biochemical, cellular and molecular mechanisms that underlie plasticity induced in the central nervous system (CNS) in response to noxious peripheral stimulation. Finally, we examine theories which have been proposed to explain how injury or noxious stimulation lead to alterations in CNS function which influence subsequent pain experience.
A Micromachined Sparse-Cell Isolation Device: Application in Prenatal Diagnostics (2006)

Fetal cells can be isolated using several enrichment methods, however, since no technique to specifically isolate and use them for genetic diagnosis has reached clinical practice, prenatal diagnosis currently requires invasive procedures. A micromachined device to fractionate whole blood using physical means to enrich for and/or isolate rare cell types from peripheral circulation was designed. It has arrays of four successively narrower channels, each consisting of a 2-D array of columns. Current devices have channels ranging in width from 15µm-2.5µm, and are 5µm deep. Fetal nucleated red blood cells were isolated from cord blood reproducibly and molecular analysis confirmed their origin without contamination from maternal DNA. Future studies will provide methods to detect fetal cells from maternal circulation using a non-invasive approach, the risk for fetal loss will be eliminated, and test costs will be decreased.
Gene targeting with a replication-defective adenovirus vector (1995)

Wide application of the gene-targeting technique has been hampered by its low level of efficiency. A replication-defective adenovirus vector was used for efficient delivery of donor DNA in order to bypass this problem. Homologous recombination was selected between a donor neo gene inserted in the adenovirus vector and a target mutant neo gene on a nuclear papillomavirus plasmid. These recombinant adenoviruses allowed gene transfer to 100% of the treated cells without impairing their viability. Homologous recombinants were obtained at a level of frequency much higher than that obtained by electroporation or a calcium phosphate procedure. The structure of the recombinants was analyzed in detail after recovery in an Escherichia coli strain. All of the recombinants examined had experienced a precise correction of the mutant neo gene. Some of them had a nonhomologous rearrangement of their sequences as well. One type of nonhomologous recombination took place at the end of the donor-target homology. The vector adenovirus DNA was inserted into some of the products obtained at a high multiplicity of infection. The insertion was at the end of the donor-target homology with a concomitant insertion of a 10-bp-long filler sequence in one of the recombinants. The possible relationship between these rearrangements and the homologous recombination is discussed. These results demonstrate the applicability of adenovirus-mediated gene delivery in gene targeting and gene therapy.
Pomalidomide alone or in combination with low-dose dexamethasone in relapsed and refractory multiple myeloma: a randomized phase 2 study (2014)

This multicenter, open-label, randomized phase 2 study assessed the efficacy and safety of pomalidomide (POM) with/without low-dose dexamethasone (LoDEX) in patients with relapsed/refractory multiple myeloma (RRMM). Patients who had received ≥2 prior therapies (including lenalidomide [LEN] and bortezomib [BORT]) and had progressed within 60 days of their last therapy were randomized to POM (4 mg/day on days 1-21 of each 28-day cycle) with/without LoDEX (40 mg/week). The primary end point was progression-free survival (PFS). In total, 221 patients (median 5 prior therapies, range 1-13) received POM+LoDEX (n = 113) or POM (n = 108). With a median follow-up of 14.2 months, median PFS was 4.2 and 2.7 months (hazard ratio = 0.68, P = .003), overall response rates (ORRs) were 33% and 18% (P = .013), median response duration was 8.3 and 10.7 months, and median overall survival (OS) was 16.5 and 13.6 months, respectively. Refractoriness to LEN, or resistance to both LEN and BORT, did not affect outcomes with POM+LoDEX (median PFS 3.8 months for both; ORRs 30% and 31%; and median OS 16 and 13.4 months). Grade 3-4 neutropenia occurred in 41% (POM+LoDEX) and 48% (POM); no grade 3-4 peripheral neuropathy was reported. POM+LoDEX was effective and generally well tolerated and provides an important new treatment option for RRMM patients who have received multiple prior therapies. This trial was registered at www.clinicaltrials.gov as #NCT00833833.
Allogeneic cytotoxic T-cell therapy for EBV-positive posttransplantation lymphoproliferative disease: results of a phase 2 multicenter clinical trial (2007)

We present the results of a multicenter clinical trial using Epstein-Barr virus (EBV)-specific cytotoxic T lymphocytes (CTLs) generated from EBV-seropositive blood donors to treat patients with EBV-positive posttransplantation lymphoproliferative disease (PTLD) on the basis of the best HLA match and specific in vitro cytotoxicity. Thirty-three PTLD patients who had failed on conventional therapy were enrolled. No adverse effects of CTL infusions were observed and the response rate (complete or partial) in 33 patients was 64% at 5 weeks and 52% at 6 months. Fourteen patients achieved a complete remission, 3 showed a partial response, and 16 had no response at 6 months (5 died before completing treatment). At 5 weeks, there was a significant trend toward better responses with higher numbers of CD4(+) cells in infused CTL lines (P = .001) that were maintained at 6 months (P = .001). Patients receiving CTLs with closer HLA matching responded better at 6 months (P = .048). Female patients responded better than male patients, but the differences were not statistically significant. Our results show that allogeneic CTLs are a safe and rapid therapy for PTLD, bypassing the need to grow CTLs for individual patients. The response rate in this poor prognosis patient group is encouraging.
Recent Progress in the Development of Inhibitors of the Hepatitis C Virus RNA-Dependent RNA Polymerase (2007)

The global prevalence of hepatitis C virus (HCV) infection and the serious consequences associated with the chronic state of the disease have become a worldwide health problem. A combination therapy comprising Interferon-alpha and Ribavirin represents the current standard treatment for chronic HCV infection, although it has demonstrated limited success and causes serious side effects. Promising alternative approaches toward the control of HCV infection include the development of small molecule inhibitors of viral enzymes interfering with the essential steps in the life cycle of the virus. In this review we will focus on inhibitors of the HCV-encoded NS5B RNA-dependent RNA polymerase (NS5B RdRp) which is essential for viral replication and has been recognized as a prime target for therapeutic intervention.
Substrate Analogues for an RNA-Editing Adenosine Deaminase:  Mechanistic Investigation and Inhibitor Design (2003)

ADARs are adenosine deaminases that act on RNA and are responsible for RNA-editing reactions that occur in eukaryotic mRNAs, including the mRNAs of glutamate and serotonin receptors. ADARs capable of editing biologically relevant RNA substrates have been identified. In addition, the consequence of the RNA-editing reaction on the function of the gene product is known in several cases. However, our understanding of the chemical mechanism of the ADAR-catalyzed adenosine deamination in RNA is lagging. By studying analogues of a naturally occurring substrate for ADAR2, we infer features of the enzyme's active site and reaction mechanism. 8-Aza substitution at adenosine in various RNA substrates accelerates the rate of deamination at these sites by ADAR2 (2.8-17-fold). The magnitude of this "aza effect" depends on the RNA structural context of the reacting nucleotide. N(6)-Methyladenosine in RNA is a slow substrate for ADAR2 (rate is 2% that of adenosine), with no product observed with N(6)-ethyladenosine, suggesting a limited size of the leaving group pocket. 2,6-Diaminopurine ribonucleoside in RNA is not a substrate for ADAR, in contrast to adenosine deaminase (ADA), which catalyzes a similar reaction on nucleosides. This and other results indicate that ADAR2 uses a base recognition strategy different from that of ADA. Consistent with the large 8-aza effect observed for the ADAR2 reaction, we find that 8-azanebularine, as the free nucleoside, inhibits the ADAR2 reaction (IC(50) = 15 +/- 3 mM) with no inhibition observed with nebularine or coformycin.
Novel Synthesis of Naphthobenzazepines from N‐Bromobenzylnaphthylamines by Regioselective C—H Activation Utilizing the Intramolecular Coordination of an Amine to Pd. (2003)

Abstract For Abstract see ChemInform Abstract in Full Text.
Patterning of functional antibodies and other proteins by photolithography of silane monolayers. (1996)

We have demonstrated the assembly of two-dimensional patterns of functional antibodies on a surface. In particular, we have selectively adsorbed micrometer-scale regions of biotinylated immunoglobulin that exhibit specific antigen binding after adsorption. The advantage of this technique is its potential adaptability to adsorbing arbitrary proteins in tightly packed monolayers while retaining functionality. The procedure begins with the formation of a self-assembled monolayer of n-octadecyltrimethoxysilane (OTMS) on a silicon dioxide surface. This monolayer can then be selectively removed by UV photolithography. Under appropriate solution conditions, the OTMS regions will adsorb a monolayer of bovine serum albumin (BSA), while the silicon dioxide regions where the OTMS has been removed by UV light will adsorb less than 2% of a monolayer, thus creating high contrast patterned adsorption of BSA. The attachment of the molecule biotin to the BSA allows the pattern to be replicated in a layer of streptavidin, which bonds to the biotinylated BSA and in turn will bond an additional layer of an arbitrary biotinylated protein. In our test case, functionality of the biotinylated goat antibodies raised against mouse immunoglobulin was demonstrated by the specific binding of fluorescently labeled mouse IgG.
A mutant of human insulin‐like growth factor II (IGF II) with the processing sites of proinsulin (1992)

A mutant of human insulin-like growth factor II (IGF II) was constructed by site-directed mutagenesis: the nucleotides coding for Ser33 and Ser39 were changed to yield Arg and Lys, respectively, thus creating two pairs of basic residues, Arg-Arg and Lys-Arg, as flanking sequences of the remaining C domain. [Arg33, Lys39]IGF II was expressed in NIH-3T3 cells as a processed two-chain peptide with a deletion of amino acid residues 37-40 and crosslinked by three disulfide bonds. This des(37-40)[Arg33]IGF II showed 3.6-fold and 7.4-fold reduced affinities to the type 1 and type 2 IGF receptor overexpressing cells, respectively, whereas the thymidine incorporation potency was the same as that of wild-type IGF II. We speculate that the discrepancy between the reduced binding to the type 1 IGF receptor and the full thymidine incorporation potency is due to the 6.1-fold reduced affinity of the expressed mutant to the co-expressed IGF binding protein 3 (IGFBP-3). The results suggest that des(37-40)[Arg33]IGF II assumes a conformation very similar to IGF II, and that the entire length of the C domain is not essential for biological activity.
Protean Manifestations of Pylethrombosis (1985)

Thirty-four adult patients with portomesenteric venous occlusion (PVO) were reviewed. In 11 with hepatic cirrhosis, PVO was usually heralded by worsening ascites often with varix hemorrhage; mortality was high. Four with isolated portal block had varix hemorrhage without ascites. All of these patients survived despite recurrent hematemesis when portal decompression was not feasible in two patients. Eight others (5 agnogenic and 3 with hypercoagulability), experienced sudden abdominal pain with a clot typically propagated into mesenteric tributaries with ileojejunal infarction; survival was related to the promptness of operation and the extent of bowel ischemia. Of five patients with intraabdominal sepsis and pylephlebitis, only one survived. In the final six patients, PVO occurred with intraabdominal carcinoma. Five had progressive ascites, cachexia, and an early death. Imaging techniques included plain and contrast roentgenograms, ultrasonography, and for definitive diagnosis direct portography (operative or splenoportogram), indirect portography (splanchnic arteriovenogram), and computed tomography. Thirteen of 34 patients had ascites, and in nine of 11 patients examined, protein concentration of ascitic fluid was extremely low (less than 0.6 g/dl). Clinical presentation of PVO varies, depending on acuteness and extent of visceral venous blockade, severity of portal hypertension, auxiliary venous collateralization, and regional lymph flow. Inciting factors include endothelial damage and blood hypercoagulability from trauma, infection, stagnant circulation, blood dyscrasia, and malignancy. Improved imaging now allows early diagnosis.
A robust, catalytic metal–organic framework with open 2,2′-bipyridine sites (2014)

We report two synthetic approaches to prepare a highly crystalline Zr(IV)-based metal-organic framework (MOF) containing open 2,2'-bipyridine (bpy) chelating sites. The resulting UiO-67-bpydc readily forms complexes with PdCl2 to produce a MOF that exhibits efficient and recyclable catalytic activity for the Suzuki-Miyaura cross-coupling reaction.
Field induced ion evaporation from liquid surfaces at atmospheric pressure (1979)

A mass spectrometer system which is capable of sampling ions directly from an atmospheric pressure source has been constructed and used to investigate ions which are evaporated from the surface of highly charged water droplets. Solutions of electrolytes are sprayed into the air, and a large charge imparted to the droplets by induction; an electric field applied across the plume of evaporating spray extracts small ions, probably already clustered with solvent molecules, which are drawn through a 25 μm orifice into the vacuum chamber. Differential pumping is applied and the ions are focused into a quadrupole mass filter. Approximately 30 univalent anions and cations of various sizes and structures have been tested, and almost all have been observed to evaporate; significant exceptions are Ag+, Tl+, and Cu+. Furthermore, certain molecules such as urea and acetanilide, when present as neutrals in the sprayed water, are observed to remain attached to the ions when these evaporate. The experimental results are discussed: ion mass spectra are interpreted in terms of ion evaporation (or field emission) and ion–molecule reactions in gas phase, and the potential value of the process for ion research and analytical applications is considered. The main features of the experimental results are consistent with the predictions of the theory developed in a previous paper by the authors.
A chip-scale universal detector for electrophoresis based on backscattering interferometry (2000)

An on-chip detector based on backscatter interferometry has been developed to perform sub-nanoliter volume refractive index measurements. The detection system consists of a simple, folded optical train based on the interaction of a laser beam and an etched channel in a silica (glass) plate. This etched channel is composed of two radii joined by a flat portion which define a curved surface in the shape of a half cylinder in a silica (glass) plate. The backscattered light from the channel takes on the form of a high contrast interference pattern that contains information related to the bulk properties of the fluid located within the probe volume. Positional changes of the interference pattern extrema (fringes) allow for the determination of refractive index changes at the 10(-6) level in a detection volume of 188 x 10(-12) L. Under capillary electrophoresis (CE) conditions, the injected mass detection limits for small molecules with little native absorption ranges from 530 fmol (0.18 ng) for sucrose to 720 fmol (0.43 nanograms) for raffinose. Fluorescein was also used to evaluate the technique for universal CE and under further optimized conditions can be quantified at the 150 microM level. Separation performance for the solutes tested ranged from about 2300 to 15,500 plates or 61,000 to 400,000 N m-1. The results presented here indicate there is potential for using the simple optical train of backscattering interferometry for on-chip universal solute analysis.
Colorectal cancer intrinsic subtypes predict chemotherapy benefit, deficient mismatch repair and epithelial‐to‐mesenchymal transition (2013)

In most colorectal cancer (CRC) patients, outcome cannot be predicted because tumors with similar clinicopathological features can have differences in disease progression and treatment response. Therefore, a better understanding of the CRC biology is required to identify those patients who will benefit from chemotherapy and to find a more tailored therapy plan for other patients. Based on unsupervised classification of whole genome data from 188 stages I-IV CRC patients, a molecular classification was developed that consist of at least three major intrinsic subtypes (A-, B- and C-type). The subtypes were validated in 543 stages II and III patients and were associated with prognosis and benefit from chemotherapy. The heterogeneity of the intrinsic subtypes is largely based on three biological hallmarks of the tumor: epithelial-to-mesenchymal transition, deficiency in mismatch repair genes that result in high mutation frequency associated with microsatellite instability and cellular proliferation. A-type tumors, observed in 22% of the patients, have the best prognosis, have frequent BRAF mutations and a deficient DNA mismatch repair system. C-type patients (16%) have the worst outcome, a mesenchymal gene expression phenotype and show no benefit from adjuvant chemotherapy treatment. Both A-type and B-type tumors have a more proliferative and epithelial phenotype and B-types benefit from adjuvant chemotherapy. B-type tumors (62%) show a low overall mutation frequency consistent with the absence of DNA mismatch repair deficiency. Classification based on molecular subtypes made it possible to expand and improve CRC classification beyond standard molecular and immunohistochemical assessment and might help in the future to guide treatment in CRC patients.
Enzymes of the biosynthesis of octadecanoid‐derived signalling molecules (2001)

It is known that octadecanoids, i.e. jasmonic acid and related compounds are involved in plant defence reactions against (1) microbial pathogens, (2) herbivores and (3) damage by UV-B or UV-C light as well as (4) senescence and (5) mechanotransduction. Jasmonic acid is likely to occur ubiquitously in the plant kingdom, and it has also been found in some fungi. The pathway of octadecanoid biosynthesis was elucidated in the early 80s by Vick and Zimmerman. This review summarizes recent progress in the identification and characterization of octadecanoid biosynthetic enzymes and in the understanding of the regulation of octadecanoid biosynthesis.
A novel guidewire approach for handling acute-angle bifurcations: reversed guidewire technique with adjunctive use of a double-lumen microcatheter. (2013)

Guidewire manipulation to negotiate branches originating at an acute angle from the parent artery is a frequently encountered challenge by the interventional cardiologist in clinical practice. To date, several methods have been developed, but none of them has a definitive success rate. Here, we report a technique for negotiating extremely angulated vascular bifurcations, with which we have achieved a high rate of success in percutaneous coronary intervention. This technique involves combining a reversed guidewire technique with a double-lumen multifunctional probing microcatheter. We present the cases of 3 patients successfully treated using this technique.
Transplantation in miniature swine. IX. Swine histocompatibility antigens: isolation and purification of papain-solubilized SLA antigens. (1981)

Histocompatibility antigens have been purified by papain treatment of crude cellular membranes obtained from spleen and mesenteric lymph nodes of individual miniature swine that are homozygous at the major histocompatibility complex. The purification protocol included ultracentrifugation, gel filtration, ion-exchange chromatography, and in some instances preparative isoelectric focusing. This procedure was applied to the preparation of sLA antigens from the 3 haplotypes available in our partially inbred miniature swine herd. The purity of the SLAdd molecules was evidenced by: 1) a single activity peak of approximately 50,000 daltons on gel-permeation chromatography; 2) the antigen elution as a symmetrical peak from ion-exchange resins and from isoelectric focusing columns; 3) the presence of 2 predominant polypeptide chains on SDS-PAGE at apparent m.w. 43,000 and 13,000 daltons; and 4) specific immunoprecipitations by alloantisera and by anti-beta 1 microglobulin antisera. The antigenic activity of SLA products was analyzed by inhibition of complement-mediated cytotoxicity and by removal on anti-beta 2-microglobulin affinity columns. Heavy and light chains were separated by gel-filtration on Sephacryl S-200 in 6 molar guanidine. These SLA products, which have thus been shown to be pure by a variety of criteria, are now readily available for structural analysis and for analysis of biologic activity.