gebhart/patrepeval huggingface dataset:
Treatment of rheumatoid arthritis with monoclonal CD4 antibody M‐T151. Clinical results and immunopharmacologic effects in an open study, including repeated administration (1991)

Recent experimental and clinical data point to the T helper lymphocyte subset as playing a central role in the pathogenesis of rheumatoid arthritis (RA). Thus, a therapeutic strategy aimed specifically at the CD4 T cell subset is warranted. We treated patients with active RA for 7 days with a daily dose of 20 mg of CD4 monoclonal antibody M-T151, administered intravenously over 30 minutes. There were no negative side effects. According to changes in the combined parameters of Ritchie articular index, pain assessment, grip strength, and morning stiffness, 6 patients had a good response. Clinical improvement was greatest approximately 2 weeks after termination of the therapy and lasted from 4 weeks to 6 months. Of the serologic parameters of inflammation, only the C-reactive protein level improved in the patients with a favorable response. Close immunologic monitoring revealed a transient, selective depletion of CD4+ T cells after each infusion. During the entire treatment period, residual circulating CD4+ cells were found to be coated with CD4 antibody, whereas free antibody was detected in the serum only for approximately 8 hours after each infusion. Immediately after infusion, soluble CD4 antigen appeared in the serum. In addition to the cell-bound CD4 antibody, complement components could be detected on the surface of the remaining CD4+ cells. The proliferative response of peripheral blood mononuclear cells to purified protein derivative was significantly diminished 4 weeks after cessation of antibody treatment. Six patients showed a weak antibody response to mouse immunoglobulin. In 4 of the responders who received a second course of therapy (2 of them as outpatients), a therapeutic effect was noted that was similar to that after the first course. Only 1 patient, who had low titers of serum IgE anti-mouse Ig antibodies, showed a mild anaphylactic reaction at the end of the second course of therapy. Treatment of RA with the monoclonal CD4 antibody M-T151 seems to be a promising alternative, although the optimal dose and the regimen of administration are still to be defined.
Characterization of 1-chlorohexane halidohydrolase, a dehalogenase of wide substrate range from an Arthrobacter sp (1987)

1-Chlorohexane halidohydrolase from Arthrobacter sp. strain HA1 was purified to homogeneity by fractional precipitation, ion-exchange chromatography, gel filtration, and high-performance liquid chromatography gel filtration. The enzyme was a monomer with a molecular weight of about 37,000; its amino acid composition and N-terminal sequence were determined. The enzyme had a broad optimum around pH 9.5, a temperature optimum near 50 degrees C, an activation energy of 40 kJ/mol, and a molecular activity of 0.9 kat/mol. The substrate range of the enzyme included at least 50 halogenated compounds. 1-Chloroalkanes (C3 to C10), 1-bromoalkanes (C1 to C9), and 1-iodoalkanes (C1 to C7), but no 1-fluoroalkane, were substrates. Subterminally substituted, branched-chain, and nonsaturated haloalkanes were dehalogenated. Some halogenated aromatic substrates, e.g., bromobenzene and benzyl bromide, were hydrolyzed. Several alpha,omega-dihaloalkanes were subject to double dehalogenation. Thus, 1,2-dibromoethane was hydrolyzed first to 2-bromoethanol and then to 1,2-dihydroxyethane. Crude extracts of strain HA1 were found to contain a debrominase that cleaved bromoalkanes with long alkyl chains.
Autolyzed Antigen-Extracted Allogeneic Bone for Bridging Segmented Diaphyseal Bone Defects in Rabbits (1988)

The autolyzed antigen-extracted allogeneic (AAA) bone implant was placed into a 17-mm long diaphyseal periosteum-free defect in the radius in 27 rabbits. The animals were observed physically and roentgenologically every week. The continuity of the radius was evaluated macroscopically and histologically. Maximum length of the follow-up period was 114 days. The AAA implants were progressively resorbed and replaced by the recipient's bone growing from fragments of radius, restoring the continuity of diaphysis. Osteoinductive activity of the implant was transferred across a tube of a polyamide vascular prosthesis. There were no appreciable histologic signs or immune of foreign-body reaction.
Pharmacology of the octopamine receptor from locust central nervous tissue (OAR3) (1995)

1. The present study characterized highly effective agonists from different classes of compounds for the neuronal octopamine receptor (OAR3) of the migratory locust (Locusta migratoria L.). Biogenic amines and phenyliminoimidazolidines (PIIs) were employed for the study of structure-activity relationships. 2. The highest affinity PIIs were predominantly those with substitutions at the positions 2 and 4 of the phenolic ring (e.g. NC 7, KI = 0.3 nM, NC 8, KI = 0.81 nM). Substitutions at these positions always had positive effects on the affinity of the respective agonists. 3. Substitutions at the positions 3, 5 and 6, however, always had negative effects on the affinity. At the position one of the phenolic ring, heterocyclic substituents are preferred. 4. Some PIIs had a more than 30 times higher affinity for OARs than for alpha-adrenoceptors which are the vertebrate homologues of the insect octopamine receptors. 5. The only non-PII with subnanomolar affinity was the aminooxazoline derivative AC 6 (KI = 0.92 nM). 6. A variety of substances with known insecticidal activity such as chlordimeform, demethylchlor-dimeform, amitraz or AC 6 had high affinity for the locust neuronal octopamine receptor.
Density dependence of the room temperature thermal conductivity of atomic layer deposition-grown amorphous alumina (Al2O3) (2014)

We report on the thermal conductivity of atomic layer deposition-grown amorphous alumina thin films as a function of atomic density. Using time domain thermoreflectance, we measure the thermal conductivity of the thin alumina films at room temperature. The thermal conductivities vary ∼35% for a nearly 15% change in atomic density and are substrate independent. No density dependence of the longitudinal sound speeds is observed with picosecond acoustics. The density dependence of the thermal conductivity agrees well with a minimum limit to thermal conductivity model that is modified with a differential effective-medium approximation.
Spotlight on fumarates. (2008)

The recent years have witnessed great efforts in establishing new therapeutic options for multiple sclerosis (MS). There is a clear need for more effective, safe and at the same time orally available treatment options. Here we review the potential of fumaric acid esters (FAE) as a new therapeutic option for MS. FAE have been claimed to possess immunomodulatory properties and are already in clinical use as second-line therapy for severe systemic psoriasis. They also displayed beneficial effects in experimental autoimmune encephalomyelitis (EAE), a model mimicking many aspects of MS. In addition, FAE may also act on the blood-brain barrier and exert neuroprotective properties via activation of anti-oxidative pathways. A first magnetic resonance imaging (MRI) based Phase II study in relapsing-remitting MS (RRMS) revealed a dose-dependent, significant reduction of brain lesion activity for BG-12, a dimethyl FAE compound. Currently, two multicentre, Phase III studies for testing clinical efficacy in RRMS are initiated. In view of their profile, FAE compounds may have the potential to add to our therapeutic options in RRMS in the future.
Recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) shortens the period of neutropenia after autologous bone marrow transplantation in a primate model. (1987)

The effect of granulocyte-macrophage colony-stimulating factor (GM-CSF) on hematopoietic reconstitution after autologous bone marrow transplantation was evaluated in a primate model. Animals were given a continuous intravenous infusion of recombinant human GM-CSF for several days both before and after transplantation or only after the transplant procedure. Marrow ablation was accomplished by total body irradiation. In both groups of animals, the neutrophil count reached 1,000/mm3 by 8-9 d posttransplant compared with an interval of 17 and 24 d for two concurrent controls. After withdrawal of GM-CSF, neutrophil counts fell to values comparable to those observed in untreated controls. Accelerated recovery of platelet production was also observed in four of the five animals. Two additional animals were initially given GM-CSF several weeks posttransplantation because of inadequate engraftment. Prompt and sustained increases in neutrophil and platelet counts were observed. We conclude that GM-CSF may be useful in accelerating bone marrow reconstitution.
Latent Fingerprint Chemical Imaging by Mass Spectrometry (2008)

Latent fingerprints (LFPs) potentially contain more forensic information than the simple identification of the subject; they may contain evidence of contacts with explosives or substances of abuse. Chemical information can also be useful in resolving overlapping LFPs from different individuals. We used desorption electrospray ionization mass spectrometry in an imaging mode to record compound-specific chemical fingerprints.
Analysis of potential biomarkers of estrogen-initiated cancer in the urine of Syrian golden hamsters treated with 4-hydroxyestradiol (2001)

Estrone (E1) and 17beta-estradiol (E2) are metabolized to catechol estrogens (CE), which may be oxidized to semiquinones and quinones (CE-Q). CE-Q can react with glutathione (GSH) and DNA, or be reduced to CE. In particular, CE-3,4-Q react with DNA to form depurinating adducts (N7Gua and N3Ade), which are cleaved from DNA to leave behind apurinic sites. We report the determination of 22 estrogen metabolites, conjugates and adducts in the urine of male Syrian golden hamsters treated with 4-hydroxyestradiol (4-OHE2). After initial purification, urine samples were analyzed by HPLC with multichannel electrochemical detection and by capillary HPLC/tandem mass spectrometry. 4-Hydroxyestrogen-2-cysteine [4-OHE1(E2)-2-Cys] and N-acetylcysteine [4-OHE1(E2)-2-NAcCys] conjugates, as well as the methoxy CE, were identified and quantified by HPLC, whereas the 4-OHE1(E2)-1-N7Gua depurinating adducts and 4-OHE1(E2)-2-SG conjugates could only be identified by the mass spectrometry method. Most of the administered 4-OHE2 was metabolically converted to 4-OHE1. Formation of thioether (GSH, Cys and NAcCys) conjugates and depurinating adducts [4-OHE1(E2)-1-N7Gua] indicates that oxidation of 4-CE to CE-3,4-Q and subsequent reaction with GSH and DNA, respectively, do occur. The major conjugates in the urine were 4-OHE1(E2)-2-NACCYS: The oxidative pathway of 4-OHE1(E2) accounted for approximately twice the level of products compared with those from the methylation pathway. The metabolites and methoxy CE were excreted predominantly (>90%) as glucuronides, whereas the thioether conjugates were not further conjugated. These results provide strong evidence that exposure to 4-OHE1(E2) leads to the formation of E1(E2)-3,4-Q and, subsequently, depurinating DNA adducts. This process is a putative tumor initiating event. The estrogen metabolites, conjugates and adducts can be used as biomarkers for detecting enzymatic oxidation of estrogens to reactive electrophilic metabolites and possible susceptibility to estrogen-induced cancer.
Selective Tropism of Lymphadenopathy Associated Virus (LAV) for Helper-Inducer T Lymphocytes (1984)

Lymphadenopathy associated virus ( LAV ) has been isolated from patients with the acquired immunodeficiency syndrome (AIDS) or lymphadenopathy syndrome. Since the immune deficiency in AIDS seems to be primarily related to the defect of the helper-inducer T lymphocyte subset, the possibility that LAV is selectively tropic for this subset was investigated. Fractionation of T lymphocytes was achieved by cellular affinity chromatography with monoclonal antibodies. In a hemophilic patient who was a healthy carrier of LAV , reverse transcriptase activity and virus particles detected by electron microscopy were found only in cultures of helper-inducer lymphocytes. When infected with LAV in vitro, lymphocyte subsets from normal individuals yielded similar results. Virus production was associated with impaired proliferation, modulation of T3-T4 cell markers, and the appearance of cytopathic effects. The results provide evidence for the involvement of LAV in AIDS.
Asenapine: a novel psychopharmacologic agent with a unique human receptor signature (2008)

Asenapine is a novel psychopharmacologic agent under development for the treatment of schizophrenia and bipolar disorder. We determined and compared the human receptor binding affinities and functional characteristics of asenapine and several antipsychotic drugs. Compounds were tested under comparable assay conditions using cloned human receptors. In comparison with the antipsychotics, asenapine showed high affinity and a different rank order of binding affinities (pKi) for serotonin receptors (5-HT1A [8.6], 5-HT1B [8.4], 5-HT2A [10.2], 5-HT2B [9.8], 5-HT2C [10.5], 5-HT5 [8.8], 5-HT6 [9.6] and 5-HT7 [9.9]), adrenoceptors (alpha1 [8.9], alpha2A [8.9], alpha2B [9.5] and alpha2C [8.9]), dopamine receptors (D1 [8.9], D2 [8.9], D3 [9.4] and D4 [9.0]) and histamine receptors (H1 [9.0] and H2 [8.2]). It had much lower affinity (pKi<or=5) for muscarinic receptors and was the only agent with affinity for H2 receptors. Relative to its D2 receptor affinity, asenapine had a higher affinity for 5-HT2C, 5-HT2A, 5-HT2B, 5-HT7, 5-HT6, alpha2B and D3 receptors, suggesting stronger engagement of these targets at therapeutic doses. Asenapine behaved as a potent antagonist (pKB) at 5-HT1A (7.4), 5-HT1B (8.1), 5-HT2A (9.0), 5-HT2B (9.3), 5-HT2C (9.0), 5-HT6 (8.0), 5-HT7 (8.5), D2 (9.1), D3 (9.1), alpha2A (7.3), alpha2B (8.3), alpha2C (6.8) and H1 (8.4) receptors. These functional effects differed from those of risperidone (pKB<5 for 5-HT6) and olanzapine (pKB<5 for 5-HT1A and alpha2). Our results indicate that asenapine has a unique human receptor signature, with binding affinity and antagonistic properties that differ appreciably from those of antipsychotic drugs.
Systems Biology: A Brief Overview (2002)

To understand biology at the system level, we must examine the structure and dynamics of cellular and organismal function, rather than the characteristics of isolated parts of a cell or organism. Properties of systems, such as robustness, emerge as central issues, and understanding these properties may have an impact on the future of medicine. However, many breakthroughs in experimental devices, advanced software, and analytical methods are required before the achievements of systems biology can live up to their much-touted potential.
Liver-intestine cadherin: molecular cloning and characterization of a novel Ca(2+)-dependent cell adhesion molecule expressed in liver and intestine. (1994)

A novel member of the cadherin family of cell adhesion molecules has been characterized by cloning from rat liver, sequencing of the corresponding cDNA, and functional analysis after heterologous expression in nonadhesive S2 cells. cDNA clones were isolated using a polyclonal antibody inhibiting Ca(2+)-dependent intercellular adhesion of hepatoma cells. As inferred from the deduced amino acid sequence, the novel molecule has homologies with E-, P-, and N-cadherins, but differs from these classical cadherins in four characteristics. Its extracellular domain is composed of five homologous repeated domains instead of four characteristic for the classical cadherins. Four of the five domains are characterized by the sequence motifs DXNDN and DXD or modifications thereof representing putative Ca(2+)-binding sites of classical cadherins. In its NH2-terminal region, this cadherin lacks both the precursor segment and the endogenous protease cleavage site RXKR found in classical cadherins. In the extracellular EC1 domain, the novel cadherin contains an AAL sequence in place of the HAV sequence motif representing the common cell adhesion recognition sequence of E-, P-, and N-cadherin. In contrast to the conserved cytoplasmic domain of classical cadherins with a length of 150-160 amino acid residues, that of the novel cadherin has only 18 amino acids. Examination of transfected S2 cells showed that despite these structural differences, this cadherin mediates intercellular adhesion in a Ca(2+)-dependent manner. The novel cadherin is solely expressed in liver and intestine and was, hence, assigned the name LI-cadherin. In these tissues, LI-cadherin is localized to the basolateral domain of hepatocytes and enterocytes. These results suggest that LI-cadherin represents a new cadherin subtype and may have a role in the morphological organization of liver and intestine.
Characterization of an Ammonium Transport Protein from the Peribacteroid Membrane of Soybean Nodules (1998)

Nitrogen-fixing bacteroids in legume root nodules are surrounded by the plant-derived peribacteroid membrane, which controls nutrient transfer between the symbionts. A nodule complementary DNA (GmSAT1) encoding an ammonium transporter has been isolated from soybean. GmSAT1 is preferentially transcribed in nodules and immunoblotting indicates that GmSAT1 is located on the peribacteroid membrane. [14C]methylammonium uptake and patch-clamp analysis of yeast expressing GmSAT1 demonstrated that it shares properties with a soybean peribacteroid membrane NH4<SUP ARRANGE="STAGGER">+ channel described elsewhere. GmSAT1 is likely to be involved in the transfer of fixed nitrogen from the bacteroid to the host.
A Sub-&#x03BC;A fast-settling current-programmed pixel circuit for AMOLED displays (2007)

Current-programmed active matrix organic light emitting diode (AMOLED) displays have been valued for their immunity to spatial mismatch, differential aging, and temperature variation. However, the long settling time particularly at small current levels and large parasitic capacitance can be a constraint. This paper presents a new current-programmed pixel circuit that improves the settling time while preserving the stability of current programming. The pixel circuit was fabricated in amorphous silicon technology. The settling time of the new pixel circuit can be as low as 20 mus whereas the settling time of conventional current-programmed pixel is more than 2 ms.
Interaction of tobramycin and pH in cultured chick tibiae (1996)

The toxicity of tobramycin at concentrations released from antibiotic-impregnated polymethylmethacrylate beads was determined using cultured embryonic chick tibiae. Because previous results from this laboratory have shown that osteoblast metabolism is inhibited at low pH and because of the potential for a low local pH in infected bone, the antibiotic was tested in medium with pH values from 6.8 to 7.4. Bone metabolism was evaluated by measuring the rates of glycolysis (lactate production), protein synthesis ([3H]proline uptake), and collagen synthesis ([3H]proline hydroxylation). Tobramycin at the concentrations released from the beads (1.0-1.5 mg/ml) contributed to lowering the pH of the medium. At pH 7.4, the antibiotic produced as much as a 30, 39, and 48% decrease in glycolysis, protein synthesis, and collagen synthesis, respectively. Tibiae exposed to tobramycin for 3 days, followed by 2 days without the antibiotic, showed only a partial recovery from its toxic effects. Although tobramycin was relatively less toxic in an acidic environment, the overall metabolic activity of the bones was poorest when the tobramycin concentration was high (2.0 mg/ml) and pH was low (6.8). The results of this study support the following conclusions: (a) tobramycin at high concentrations is toxic to bone, (b) a combination of high tobramycin concentration and low pH in the bone microenvironment may greatly inhibit bone metabolism, and (c) treatment and prevention of osteomyelitis by means of tobramycin-impregnated beads may be augmented by preventing the pH from decreasing in traumatized areas.
Rapid Method for Screening Dried Blood Samples on Filter Paper for Human Immunodeficiency Virus Type 1 DNA (1999)

PCR is a highly sensitive method for the detection of human immunodeficiency virus type 1 (HIV-1) nucleic acids in blood mononuclear cells and plasma. However, blood separation techniques require extensive laboratory support systems and are difficult when a limited volume of blood is available, which is often the case for infants. The use of blood samples stored on filter paper has many advantages for the detection of perinatal HIV-1 infection, but current methods require extraction and purification of target DNA prior to PCR amplification. We report a highly sensitive and rapid method for the extraction and detection of HIV-1 DNA in infant blood samples stored on filter papers. Because this rapid protocol does not involve steps for the removal of potential inhibitors of the PCR, the highest sensitivity is achieved by testing the filter paper lysate in quadruplicate. Assays for HIV-1 DNA were done by using nested PCR techniques that amplify HIV-1 gag DNA from blood spot samples on filter paper and from corresponding viably frozen mononuclear cells separated from venous blood samples obtained from 111 infants born to HIV-1-seropositive mothers. PCR results with blood from filter papers showed 100% specificity (95% confidence internal [CI] 93.1 to 100%) and 96% (95% CI, 88.65 to 98.9%) and 88% (95% CI, 79.2 to 94.5%) sensitivity (for quadruplicate and duplicate tests, respectively) compared to PCR results with blood mononuclear cells. Moreover, this method could detect HIV-1 sequences of multiple subtypes.
Apolipoprotein E epsilon4 and the risk of dementia with stroke. A population-based investigation (1997)

The APOE epsilon4 allele is a genetic risk factor for dementia with stroke, including VaD and AD with CVD. This may imply shared genetic susceptibility to dementia associated with stroke and AD. Alternatively, the category of patients with dementia and stroke, including VaD as currently defined, may include patients with AD.
Regulation of Adenosine 3′,5′-Monophosphate-dependent Protein Kinase (1973)

Abstract In order to investigate the effects of hormones on the adenosine 3',5'-monophosphate (cAMP)-dependent protein kinase of adipose tissue, it was necessary to study the characteristics of the enzyme in crude tissue extracts. There was an apparent activation of the enzyme by NaF, but this effect was probably due to inhibition of adenosine triphosphatase activity. The activity of phosphodiesterase in the extracts was low under the conditions of the experiments. Two procedures to determine the state of activation of the protein kinase in crude extracts are described. Both procedures are based on the amounts of inactive protein kinase (holoenzyme) and active catalytic subunit present. In the first procedure the activity ratio of the protein kinase is measured, i.e. the ratio of activity in the absence to activity in the presence of cAMP. At 0° in the presence of 0.5 m NaCl the protein kinase activity ratio was not affected by dilution of the extracts. Under these conditions, when cAMP was removed by gel filtration, the activity ratio decreased only very slowly but decreased rapidly in the absence of NaCl. The salt probably inhibits association of the regulatory and catalytic subunits of the protein kinase. In the second procedure for determining the activation state of the protein kinase, crude adipose tissue extracts were chromatographed on Sephadex G-100 columns and the areas under the curves of the two peaks of enzyme activity corresponding to holoenzyme and catalytic subunit were estimated. Sodium chloride (0.5 m) at 0° inhibited the association of the protein kinase subunits during this procedure. Sephadex G-100 profiles of the protein kinase in crude extracts of heart, brain, and liver were also determined. Sodium chloride (0.5 m) was also found to increase the activity ratio of the protein kinase in the presence of cAMP. At 0° this increase occurred relatively slowly and was accompanied by an increase in cAMP binding and a decrease in the cAMP requirement for enzyme activity.