gebhart/patrepeval huggingface dataset:
Characterization of Human Sperm Surface Antigens with Monoclonal Antibodies (1983)

Monoclonal antibodies (McAb) against human ejaculated sperm were developed from mice immunized with sperm membrane preparations. A solid-phase radioimmunoassay, with dried sperm as antigen, was employed in McAb screening. The tissue and species specificity of monoclonal antibodies HS 2, 4 and 6 were evaluated after absorption of antibody preparations with heterologous sperm, human serum or seminal plasma or cells from other human organs. The sensitivity of HS 2, 4 and 6 antigens to trypsin exposure was determined: HS 4 antigen was highly sensitive while HS 2 and 6 were not. The regional distribution of McAb 4 on intact sperm cells was determined by immunofluorescence staining. HS 4 may be a sperm-coating antigen based on its presence on sperm and in seminal plasma. This possibility led to an investigation of its role in sperm capacitation. HS 4 antibody binding was reduced when capacitated sperm were compared with noncapacitated cells. HS 4 antibody, when present during capacitation and insemination, was without effect on sperm motility or fusion with zona-free hamster eggs. Trypsin removal of as much as 60% of HS 4 antigen from the cell population also did not impact on sperm function. To identify the molecular correlate of HS 4 antigen, membrane components were extracted from washed sperm with Nonidet P-40, concentrated by acetone precipitation and analyzed electrophoretically in SDS-urea on 10% polyacrylamide slab gels. Immunoassays on protein blots with peroxidase-coupled second antibody identified a single reactive species in the molecular weight range of 130,000. Multiple reactive components were detected in blot transfers of seminal plasma.
Regulation of Transfected Glycoprotein Hormone α-Gene Expression in Primary Pituitary Cell Cultures (1989)

Studies of gene regulation are greatly facilitated by the ability to transfect DNA into cultured cells. We examined a variety of transfection techniques to optimize transient expression of the human glycoprotein hormone alpha-gene in primary pituitary cells and subsequently investigated the regulation of alpha-promoter transcription. Expression vectors driven by either the rous sarcoma virus-chloramphenicol acetyl transferase (RSVCAT) or the human alpha-gene (alpha CAT) promoters were transfected into cultures of dispersed female rat pituitary cells using calcium phosphate (CaPO4), diethylaminoethyl-dextran, lipofection, and electroporation procedures. CAT activity was optimal using the CaPO4 technique, resulting in 511 +/- 49% and 57 +/- 5% conversion/100 micrograms protein/4 h for RSVCAT and alpha CAT, respectively. Immunohistochemical analyses of alpha CAT expression using anti-CAT monoclonal antibodies demonstrated that the alpha-gene promoter is expressed in pituitary cells, predominantly if not exclusively, in gonadotropes and thyrotropes. Hormonal regulation of alpha-promoter activity was assessed using both the CAT and the luciferase (LUC) reporter systems. alpha-Promoter activity was significantly (P less than 0.001) stimulated by 8-bromo-cAMP (217% increase), GnRH (75% increase), GnRH agonist analog (141% increase), and TRH (75% increase). The expression of control plasmids (RSVLUC, TKLUC, pOLUC) was not affected by treatment with these agents. We conclude that CaPO4-mediated transfection allows analyses of transient gene expression in primary pituitary cells. The alpha-promoter directs expression specifically in pituitary cells, predominantly gonadotropes and thyrotropes. alpha-Gene transcription is stimulated by GnRH, TRH, and 8-bromo-cAMP.
Detailed Morphology and Distribution of Gap Junction Protein Associated with Cells from the Intra-Articular Disc of the Rat Temporomandibular Joint (2003)

The present study details structural aspects of the cells of the rat intra-articular disc (IAD) of the temporomandibular joint. At the light and electron microscope level, the outline of the cells varied, although a number appeared oval/rounded. Ultrastructurally, the cells contained moderate amounts of the intracellular organelles associated with protein synthesis. Cell processes were not a prominent feature seen using these techniques. However, using confocal microscopy, phalloidin staining revealed the presence of numerous, actin-rich, long, thin, branching processes emanating from the cell membranes. Double staining for connexin 43 revealed that the cell processes showed dense, punctate positive staining for this gap junction protein along their whole length. These observations provide the basis for a transport mechanism for nutritive molecules from the periphery of the IAD (where blood vessels are present) to the central portions of the disc (where blood vessels are absent).
A broadband system for multifrequency static imaging in electrical impedance tomography (1992)

A widely accepted method for static imaging in electrical impedance tomography (EIT) is to measure at two frequencies. The choice of measurement frequencies is application-dependent because some different tissues cannot be distinguished when using two fixed frequencies. We have developed a system that generates signals from 8-10(3) kHz and applies two of these signals simultaneously to the body through a broadband current mirror. Great care has been taken in the design of the current injection multiplexer in order to keep the current source output capacitance as low as possible. Furthermore design of the layout of the patient interface board, in order to reduce feedthrough capacitances, also needs great care. Other parameters for driving and detection sections have been designed according to our results from FEM and circuit simulations including skin and electrode effects. Simulations using FEM with available tissue impedance data and preliminary measurements in a discrete phantom show that static imaging is possible for both the real and imaginary parts of the impedance.
Synthesis of hepadnavirus particles that contain replication-defective duck hepatitis B virus genomes in cultured HuH7 cells (1990)

To evaluate the possibility of producing transducible replication-defective hepadnaviruses, cloned mutant duck hepatitis B virus genomes were tested both for virus antigen production and viral DNA synthesis following transfection into the human hepatoma cell line HuH7. Deletion of a cis-acting 12-nucleotide sequence implicated in viral DNA synthesis, direct repeat 1 (DR1), resulted in the loss of ability to synthesize both mature viral DNA and infectious virus. The delta DR1 mutant, however, produced envelope and core antigens and was shown to provide trans-acting functions required for the assembly of infection-competent particles. Thus, mutants with mutations in viral genes could be rescued as DNA-containing viral particles after cotransfection with delta DR1. The efficiency of rescue was influenced by the site of mutation. A mutant DNA encoding truncated core and envelope proteins not only was poorly rescued but also was able to suppress the production from a wild-type DNA of infectious virus.
An immunohistological study of granulomatous prostatitis (1991)

Granulomatous prostatitis may result from tuberculosis and fungal infection and has been described following prostatic surgery. In most cases, however, the aetiology is unknown, although it may be due to a reaction to extravasated or altered prostatic secretions. We have investigated cells (macrophages, lymphocytes), serum proteins (fibrinogen, alpha 1-antitrypsin) and prostatic epithelial products (prostatic-specific antigen and prostatic acid phosphatase) in diffuse granulomatous prostatitis (3 cases), focal periacinar prostatic granulomas (9) and focal prostatic infarcts (5), using an immunohistological technique. T-lymphocytes and macrophages are present in diffuse and focal granulomatous prostatitis, but few B-lymphocytes occur. Fibrinogen-related antigen is absent from granulomas, but a small amount is present within infarcts, whereas plentiful alpha 1-antitrypsin was detected both in granulomas and infarcts. Significant reduction in prostatic-specific antigen and acid phosphatase reactivity occurs in granulomatous prostatitis. This suggests that cytokines derived from activated macrophages and T-lymphocytes may be exerting a cell regulatory effect and altering cell secretions, as well as causing destruction of the prostatic epithelium.
A mannose-specific adherence mechanism in Lactobacillus plantarum conferring binding to the human colonic cell line HT-29 (1996)

Two Lactobacillus plantarum strains of human intestinal origin, strains 299 (= DSM 6595) and 299v (= DSM 9843), have proved to be efficient colonizers of the human intestine under experimental conditions. These strains and 17 other L. plantarum strains were tested for the ability to adhere to cells of the human colonic cell line HT-29.L.plantarum 299 and 299v and nine other L. plantarum strains, including all six strains that belong to the same genetic subgroup as L. plantarum 299 and 299v, adhered to HT-29 cells in a manner that could be inhibited by methyl-alpha-D-mannoside. The ability to adhere to HT-29 cells correlated with an ability to agglutinate cells of Saccharomyces cerevisiae and erythrocytes in a mannose-sensitive manner and with adherence to D-mannose-coated agarose beads. L. plantarum 299 and 299v adhered to freshly isolated human colonic and ileal enterocytes, but the binding was not significantly inhibited by methyl-alpha-D-mannoside. Periodate treatment of HT-29 cells abolished mannose-sensitive adherence, confirming that the cell-bound receptor was of carbohydrate nature. Proteinase K treatment of the bacteria also abolished adherence, indicating that the binding involved protein structures on the bacterial cell surface. Thus, a mannose-specific adhesin has been identified in L. plantarum; this adhesin could be involved in the ability to colonize the intestine.
Metformin reverses early cortical network dysfunction and behavior changes in Huntington’s disease (2018)

Catching primal functional changes in early, 'very far from disease onset' (VFDO) stages of Huntington's disease is likely to be the key to a successful therapy. Focusing on VFDO stages, we assessed neuronal microcircuits in premanifest Hdh150 knock-in mice. Employing <i>in vivo</i> two-photon Ca<sup>2+</sup> imaging, we revealed an early pattern of circuit dysregulation in the visual cortex - one of the first regions affected in premanifest Huntington's disease - characterized by an increase in activity, an enhanced synchronicity and hyperactive neurons. These findings are accompanied by aberrations in animal behavior. We furthermore show that the antidiabetic drug metformin diminishes aberrant Huntingtin protein load and fully restores both early network activity patterns and behavioral aberrations. This network-centered approach reveals a critical window of vulnerability far before clinical manifestation and establishes metformin as a promising candidate for a chronic therapy starting early in premanifest Huntington's disease pathogenesis long before the onset of clinical symptoms.
Multiple Melanomas After Treatment for Hodgkin Lymphoma in a Non-Dutch p16-Leiden Mutation Carrier With 2 MC1R High-Risk Variants (2007)

This study shows the variability of the penetrance of the CDKN2A Leiden mutation within the same family, which could be due to genetic or exogenous factors.
Providing easier access to remote objects in client-server systems (2002)

The Java Environment for Distributed Invocation (JEDI) is efficient, dynamic and easier to use than alternative communication systems for distributed Java objects. Existing state-of-the-art mechanisms for remote method calls on Java objects, such as RMI (remote method invocation), require users to perform a complicated series of steps. Furthermore, the compiled static interfaces these systems use limit their functionality. This paper presents the design and implementation of JEDI's simpler approach utilizing dynamic proxies. We discuss a means of integrating JEDI with a publicly available CORBA object request broker (ORB), followed by the tests used to ensure the robustness of the JEDI system. Comparing this system's performance with that of other communication facilities such as UDP, TCP and RMI demonstrates the efficiency of JEDI. A calendar program illustrates the flexibility and usability tradeoffs of employing JEDI in distributed client-server applications.
Effects of the cyclosporine SDZ-PSC 833 (PSC 833) on the pharmacokinetics and toxicity of doxorubicin in mice (1994)

Gonzalez, O; Colombo, T; Imperatori, L; Zucchetti, M; de Fusco, M; d'Incalci, M Author Information
The CRF Receptor Structure, Function and Potential for Therapeutic Intervention. (2001)

Two distinct sub-types of receptor encoded by separate genes have been described to date, CRF1 and CRF2, and they belong to the Class-B subdivision within the G-protein coupled receptor (GPCR) super family. All known CRF receptors positively regulate the accumulation of cAMP in response to CRF and are therefore coupled to Gs as the major signal transduction mechanism. CRF receptors interact with two sub-families of CRF peptide ligands - mammalian hypothalamic CRFs and urocortin and secondly, non-mammalian peptides like sauvagine (frog) and urotensin-I (fish). The CRF peptide backbone tends to form one a-helical secondary structure in the central portion of the molecule, whereas the N-terminal and C-terminal regions of the peptide are not structured. Residues 1 - 8 at the N-terminal of the peptide are critical for activation of the receptor, whereas residues 11 - 41 at the C-terminal of the peptide are important for binding, especially to the N-terminal extracellular domain of the receptor. Using both agonist and antagonist peptides and heterocyclic-based antagonists combined with strategically mutated receptors, it has been possible to define binding sites located on the extracellular surface (for peptides) and within the helical domains (for the non-peptides) of the protein. There is a significant positive correlation between specific measures of CRF activation in the central nervous system and the incidence of disorders associated with the stress axis. These effects range from neuropsychiatric disorders such as anxiety or depression to somatic disorders such as dysregulation of the immune system or modulation of gastric function. The tremendous effort being put forth into the identification of high affinity, selective, safe and tolerable drug candidates acting on CRF receptors holds promise for novel therapies for some of these disorders.
Purification of A1 adenosine receptor from rat brain membranes (1989)

The A1 adenosine receptor from rat brain membranes has been purified about 50,000-fold to apparent homogeneity by sequential use of affinity chromatography on immobilized xanthine amine congener-agarose, hydroxylapatite chromatography, and reaffinity chromatography. The overall yield starting from the membranes was approximately 4%. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the purified preparation gave a broad single band of an apparent molecular weight of 34,000 either by silver staining or autoradiogram after radioiodination. The purified receptor bound approximately 24 nmol of 8-cyclopentyl-1,3-[3H]dipropylxanthine/mg of protein with a dissociation constant of 1.4 nM. This maximum specific binding value is consistent with the expected theoretical specific activity (29.4 nmol/mg) for a protein with a molecular mass of 34,000 daltons if it is assumed that there is one ligand-binding site/receptor molecule. Affinity-labeling experiments using [3H]p-phenylenediisothiocyanate-xanthine amine congener showed that the Mr = 34,000 protein band contained the ligand-binding sites. The purified receptor gave a typical A1 adenosine receptor pharmacological specificity similar to that of unpurified receptor preparations.
Bovine IgM antibodies with exceptionally long complementarity‐determining region 3 of the heavy chain share unique structural properties conferring restricted VH + Vλ pairings (2003)

Naturally occurring antibody repertoires of cattle (Bos taurus) include a group of IgMlambda antibodies with exceptionally long complementarity-determining region 3 of the heavy chain (CDR3H) segments, containing multiple Cys residues. These massive CDR3H segments will greatly influence the tertiary and quaternary structures of the bovine IgM combining sites. As an antibody's combining site is formed by both heavy and light chains, we have analyzed the nucleotide sequences and structural properties of the lambda-light chains that pair with micro -heavy chains containing exceptionally long CDR3H. There appears to be an exquisite selective pressure for the use of three V(lambda)1 genes (V(lambda)1x and two new V(lambda)1d and V(lambda)1e genes) in IgM with unusually long CDR3H. The V(lambda)1d and V(lambda)1e genes are similar to each other, but diverge from the other V(lambda)1 genes into two closely related subfamilies. The available bovine V(lambda) genes are classified into three V(lambda) gene families: V(lambda)1, V(lambda)2 and V(lambda)3 based on nucleotide similarity >/=80%. Further, analysis of total Ser content and positions of Ser residues in the sequences was found to be sufficient to classify the cattle V(lambda)1 subfamilies. Patterns of Ser residues differ for V(lambda) domains from ruminant species (e.g. cattle, sheep and goats) and other mammals (e.g. humans and mice). These 'Ser signatures' can be used to track divergent evolution in lambda-light chains. Interestingly, Ser90L in complementarity-determining region 3 of the light chain (CDR3L) occurred in all V(lambda) domains that pair with V(H) regions containing exceptionally long CDR3H. A structural role for Ser90L was revealed in homology models of V(lambda) domains, i.e. to hold the ascending polypeptide of CDR3L in a relatively tight space between the N-terminal segment and residues from CDR1L. The CDR3L of V(lambda) domains also occupied smaller volumes if paired to V(H) domains with extremely long CDR3H (>/=48 residues), and were more variable in their conformation and filled larger volumes if CDR3Hs were </=22 residues. Thus, the role of the lambda-light chains in these unusual cattle antibodies is probably to act as a relatively featureless supporting platform for the extremely long CDR3H regions, which undoubtedly are dominantly involved in binding to an antigen.
Dimethyl carbonate and phenols to alkyl aryl ethers via clean synthesis (2002)

The industrially important alkyl aryl ethers (ArOR) were selectively obtained in good yields from the O-alkylation of the corresponding phenols with the environmentally benign reagents, dimethyl carbonate or diethyl carbonate. The reactions were carried out under atmospheric pressure, in a homogenous process, without solvent and in the presence of potassium carbonate as catalyst.
LiMnPO[sub 4] as the Cathode for Lithium Batteries (2002)

Olivine has been produced using a new synthetic method. Reversible extraction and insertion of lithium into olivine at 4.1 V vs. lithium demonstrated that this material is a promising candidate for the cathode in lithium-ion batteries. When charged to 4.5 V, ca. 0.94 Li per formula unit can be extracted during the first charge. When charged to 4.8 V, 152 mAh/g was delivered in the first discharge. An overall reversible capacity of 140 mAh/g has been attained at room temperature. A flat two-phase region with open-circuit voltage V was identified. The thermal stability of the charged cathode was evaluated by thermogravimetric analysis and differential scanning calorimetry. © 2002 The Electrochemical Society. All rights reserved.
Analytical Challenges and Regulatory Requirements for Nasal Drug Products in Europe and the U.S. (2014)

Nasal drug delivery can be assessed by a variety of means and regulatory agencies, e.g., the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have published a set of guidelines and regulations proposing in vitro test methods for the characterization of nasal drug products. This article gives a summary of the FDA and EMA requirements regarding the determination of droplet size distribution (DSD), plume geometry, spray pattern and shot weights of solution nasal sprays and discusses the analytical challenges that can occur when performing these measurements. In order to support findings from the literature, studies were performed using a standard nasal spray pump and aqueous model formulations. The aim was to identify possible method-, device- and formulation-dependent influencing factors. The literature review, as well as the results from the studies show that DSD, plume geometry and spray pattern are influenced by, e.g., the viscosity of the solution, the design of the device and the actuation parameters, particularly the stroke length, actuation velocity and actuation force. The dominant factor influencing shot weights, however, is the adjustment of the actuation parameters, especially stroke length and actuation velocity. Consequently, for routine measurements assuring, e.g., the quality of a solution nasal spray or, for in vitro bioequivalence studies, the critical parameters, have to be identified and considered in method development in order to obtain reproducible and reliable results.
Potential Application of Silicified Microcrystalline Cellulose in Direct-Fill Formulations for Automatic Capsule-Filling Machines (2003)

Silicified microcrystalline cellulose (SMCC) has physico-mechanical properties that may be of advantage in hard gelatin capsule formulations. The present research was designed to evaluate and compare SMCC's performance to that of other excipients commonly used in hard gelatin capsule direct-fill formulations. All capsules were filled using a fully instrumented Zanasi LZ-64 automatic capsule-filling machine. Four grades of SMCC [SMCC 50, SMCC 90, SMCC HD90, and an experimental-grade (SMCC X)] were investigated. Anhydrous lactose (direct tableting grade), pregelatinized starch (PGS) (Starch 1500), and microcrystalline cellulose (MCC) (Emcocel 90M) were chosen as the control fillers. The following properties were measured: capsule fill weight, relative standard deviation of capsule fill weight, plug ejection force, plug maximum breaking force (MBF), and the dissolution of two marker compounds (acetaminophen and piroxicam). The MBF of capsule plugs increased with increases in compression force from 50N to 100N for all excipients. Starch 1500 and anhydrous lactose plugs exhibited the lowest MBF values. PGS, anhydrous lactose, SMCC HD90, and SMCC X consistently exhibited the lowest ejection forces under the same experimental conditions, this difference being most apparent at higher compression forces. Different patterns were observed in the way compression force affected the fill weight of the materials studied. Overall, there was no clear pattern to the way the relative standard deviation (RSD) of capsule fill weight varied with encapsulation conditions. Sodium stearyl fumarate (SSF) appeared to be somewhat more efficient at reducing the ejection force than magnesium stearate at the same level, this difference being especially apparent at the 14-mm piston height. Formulations containing either 5% piroxicam, 30% acetaminophen, or 50% acetaminophen exhibited faster drug dissolution when MCC or SMCC was the filler than when anhydrous lactose or PGS was the filler. The presence of colloidal silicon dioxide in SMCC did not appear to influence the dissolution of these drugs. The data suggest that SMCC could be a suitable direct-fill excipient for hard shell capsule formulations.