gebhart/patrepeval huggingface dataset:
Effects of Interferon-γ Therapy on Thyroid Function, T-Lymphocyte Subpopulations and Induction of Autoantibodies (1990)

Treatment with human leucocyte interferon (IFN alpha) has been associated with the development of thyroid autoimmunity and hypothyroidism, but it is not certain whether this phenomenon was a result of contamination with IFN gamma, which induced HLA class II antigen expression on T-lymphocytes. We prospectively studied 11 subjects (5 females and 6 males; mean age, 26.8 yr; range, 18-36) with chronic active hepatitis B who were randomized to receive recombinant human IFN gamma (rhIFN gamma; 10(6) U/m2.day, im, 3 times/week) for 16 weeks. Goiter was not present, and no patient had a history or family history of autoimmune diseases. Serial thyroid functions, including serum T4, T3, free thyroid hormone index, free T4 and TSH before, during, and on subsequent follow-up for a period of 1 yr were all normal. Eight patients had adequate serial samples for study of serological and lymphocyte subpopulations. None of the patients treated with rhIFN gamma developed thyroglobulin or thyroid microsomal antibodies. However, four patients developed antinuclear and smooth muscle autoantibodies during or after rhIFN gamma treatment. Treatment with rhIFN gamma resulted in a significant increase in circulating T-lymphocytes and HLA-DR-positive T-cells (P less than 0.05), with equal proportions of circulating CD4+ and CD8+ T-cells becoming DR positive. The percentage of HLA-DR-positive T-cells remained elevated after discontinuation of rhIFN gamma. Also, rhIFN gamma treatment led to a decrease in the number of circulating granulocytes and interleukin-2 receptor-positive cells. In conclusion, we did not observe any thyroid dysfunction or thyroid autoimmunity in our patients treated with the studied dose of rhIFN gamma, but induction of other autoantibodies was observed.
Evidence supporting exclusion of the DCC gene and a portion of chromosome 18q as the locus for susceptibility to hereditary nonpolyposis colorectal carcinoma in five kindreds. (1991)

Hereditary non-polyposis colorectal carcinoma (HNPCC) syndrome is characterized by early onset and multiple cancers of predominantly the proximal colon and occasionally other organs. The mode of transmission is compatible with autosomal dominant inheritance but the location and characteristics of the putative susceptibility gene are unknown. We performed linkage analyses with the aim of proving or excluding the existence of a susceptibility locus on 18q. This hypothesis was based on the frequent involvement of the DCC gene in colorectal carcinoma and on the previously reported linkage between HNPCC and the Kidd blood group locus (JK) also on 18q. Seven HNPCC families were tested with eight polymorphisms, including three from within DCC. The DCC locus could be excluded as the HNPCC susceptibility locus in five families in which the two point logarithm-of-odds scores were -3.66, -3.63, -4.12, -7.90, and -3.74 at the recombination fraction of 0.00. In the remaining two families linkage could be neither excluded nor confirmed. The added pairwise logarithm-of-odds score for all seven families was -22.65 at the recombination fraction of 0.00. Multipoint analyses of linkage in the seven families suggested exclusion of some 60 cM in the region DCC-D18S18-D18S22-D18S7 as the site for HNPCC susceptibility locus. In addition to DCC, the excluded portion comprises JK.
Biological activity of 25-hydroxycholecalciferol, a metabolite of vitamin D3. (1968)

Proceedings of the National Academy of Sciences (PNAS), a peer reviewed journal of the National Academy of Sciences (NAS) - an authoritative source of high-impact, original research that broadly spans the biological, physical, and social sciences.
A point mutation in the integrin beta 3 cytoplasmic domain (S752-->P) impairs bidirectional signaling through alpha IIb beta 3 (platelet glycoprotein IIb-IIIa) (1994)

Agonist-induced inside-out signaling results in an increased affinity of integrin alpha IIb beta 3 (platelet glycoprotein IIb-IIIa) for soluble ligands (fibrinogen [Fg] and PAC1). Ligand binding to integrins initiates outside-in signaling that leads to cellular responses such as cell spreading and focal adhesion formation. A point mutation in the beta 3 cytoplasmic domain (S752-->P) is associated with blocked inside-out alpha IIb beta 3 signaling in a variant Glanzmann's thrombasthenia. This mutation was introduced into beta 3 and cotransfected into Chinese hamster ovary cells with a chimeric alpha subunit consisting of the alpha IIb extracellular and transmembrane domains and the alpha 6B cytoplasmic domain. The substitution of the alpha IIb cytoplasmic domain with that of alpha 6 led to activation of alpha IIb beta 3 to bind PAC1, mimicking inside-out signaling. This effect was reversed by the S752-->P mutation, indicating a disruption of inside-out signaling by the mutation. In addition, transfectants expressing this beta 3 variant showed reduced alpha IIb beta 3-mediated cell spreading on immobilized Fg, focal adhesion, and fibrin clot retraction, suggesting an impairment in outside-in alpha IIb beta 3 signaling. Therefore, a single point mutation in the beta 3 cytoplasmic domain impaired bidirectional signaling through alpha IIb beta 3.
Productivity costs in patients with refractory chronic rhinosinusitis (2014)

Results from this study have demonstrated that the annual productivity cost associated with refractory CRS is $10,077.07 per patient. This substantial cost to society provides a strong incentive to optimize current treatment protocols and continue evaluating novel clinical interventions to reduce this cost.
A new marrow T cell depletion method using anti-CD6 monoclonal antibody-conjugated magnetic beads and its clinical application for prevention of acute graft-vs.-host disease in allogeneic bone marrow transplantation: results of a phase I-II trial. (1999)

We established a simple method of T cell depletion using anti-CD6 monoclonal antibody-conjugated immunomagnetic beads. Preliminary experiments using this method demonstrated that CD3+ T cells could be partially depleted without depleting CD56+ NK cells. A phase I-II clinical study was performed to assess the safety and efficacy of this partial T cell depletion method for the prevention of acute graft-vs.-host disease (GVHD) in 10 leukemia patients at high risk for GVHD (defined as 1) unrelated transplant from MLC-positive or HLA-DRB1 mismatched donor or 2) related transplant from serologically HLA-A, -B, or -DR one-locus mismatched donor). Cyclosporine (CSP) and methotrexate (MTX) were used for additional prophylaxis against GVHD in all cases. Sustained engraftment occurred in 9 of the 10 patients. Although acute GVHD developed in 6 of the 9 evaluable patients, none developed more than grade III severe acute GVHD. Five patients were alive in remission at a median follow-up of 32 months after bone marrow transplantation, and no relapse of leukemia was observed. We conclude from this pilot study that selective T cell depletion with anti-CD6 monoclonal antibody coupled with CSP and MTX posttransplant immunosuppressive therapy is safe. Further analysis of the phase II-III study is needed to confirm the effectiveness of this protocol.
Neurotensin: immunohistochemical localization in rat central nervous system. (1977)

Neurotensin immunofluorescence was examined in the rat central nervous system using a well-characterized antiserum directed against this tridecapeptide. Morphological characteristics of the fluorescence indicate its association with neuronal cell bodies and processes in the brain and with cells of the anterior pituitary. Fluorescence is seen in many brain areas, with notable densities in the substantia gelatinosa zones of the spinal cord and trigeminal nucleus, central amygdaloid nucleus, anterior pituitary, median eminence, and preoptic and basal hypothalamic areas.
Characterization of monoclonal antibody-escape mutants of tick-borne encephalitis virus with reduced neuroinvasiveness in mice. (1997)

Escape mutants of tick-borne encephalitis (TBE) virus were selected using neutralizing monoclonal antibodies (MAbs) that react with three different and previously unrecognized epitopes in the envelope protein E of TBE virus. Two of these variants (V-IC3 and V-IE3) exhibited a significantly reduced reactivity with their selecting MAbs, as determined by ELISA, whereas with one variant (V-IO3), reactivity was completely unchanged. Comparative sequence analyses demonstrated that each of the variants differed from the wild-type virus by a single amino acid substitution located at exposed positions within domains I, II and III of protein E. In the mouse model, all three mutants were still neuro-virulent but exhibited a significantly reduced neuro-invasiveness after subcutaneous inoculation. Virus replication, however, was sufficient to induce a specific antibody response. The observed alterations in virulence properties were not associated with reduced growth rates in vertebrate cell cultures, but one variant (V-IE3) exhibited a small plaque phenotype. The mutation of variant V-IO3 resulted in a temperature-sensitive phenotype and a significant elevation of the pH-threshold of the conformational change necessary for fusion activity.
Forecasting cephalosporin and monobactam antibiotic half-lives in humans from data collected in laboratory animals (1985)

The postdistribution half-lives of 10 cephalosporin and 2 monobactam antibiotics in humans were predicted from data obtained in other mammals. This forecasting was accomplished with the allometric equation t1/2 = aWb, where a is the y intercept and b is the slope obtained from the log-log plot of antibiotic half-life (t1/2) versus body weight (W). Dimensionless similarity criteria were used to produce a biological clock for ceftizoxime elimination. The creation of the biological clock, which measured physiologic time (heartbeats) rather than chronologic time (minutes), demonstrated that ceftizoxime half-life was identical in five mammals. This methodology will contribute to infectious disease research through a greater understanding of pharmacokinetic scaling in mammals.
Preparation of 125I-Catalytic Subunit of Aspartate Transcarbamylase and Its Use in Studies of the Regulatory Subunit (1973)

Abstract A quantitative specific assay for the regulatory subunit of aspartate transcarbamylase is described. The assay, in which the native enzyme will not interfere even when present in large excess, is sensitive to 5 ng of regulatory subunit at a concentration as low as 0.1 µg per mg in crude extracts. The assay utilizes a 125I-labeled catalytic subunit which combines spontaneously with regulatory subunit to form a complex which co-migrates with the native enzyme on acrylamide gel electrophoresis in a position clearly separable from the 125I-catalytic subunit. The amount of regulatory subunit can then be calculated from the known weight ratio in the enzyme complex. Mutants of Salmonella typhimurium defective in aspartate transcarbamylase activity are shown to still synthesize regulatory subunit, while a mutant constitutive for the enzymes in the pathway for pyrimidine biosynthesis is shown to produce an excess of free regulatory subunit over native enzyme. A new procedure for iodination of proteins under mild conditions is described. It utilizes a preoxidation of iodide to iodine under conditions of stoichiometric or very low excess of oxidizing agent followed by reaction with the protein. It is used on a microscale to prepare 125I-catalytic subunit having properties virtually indistinguishable from the native protein.
Ultrastructural and Morphometric Investigation of Human Brain Capillaries in Normal and Peritumoral Tissues (1997)

Capillaries of peritumoral and normal brain tissues were ultrastructurally and morphometrically investigated to evaluate the changes in peritumoral capillaries connected with the tumor-associated vasogenic edema. The endothelial cells of peritumoral capillaries showed varying thickness, electron-lucent cytoplasm, and structurally normal tight junctions. The basal lamina was thickened, rarefied, and vacuolated. The pericytes were provided with pinocytotic vesicles and phagocytic bodies. The astrocytic glia appeared empty or swollen, with few glycogen granules and a disarranged cytoskeleton; well-preserved glia was occasionally observed. The brain tissue was slightly edematous. No statistically significant differences were observed between normal and peritumoral capillaries as regards diameter, wall thickness, endothelial thickness, and endothelial vesicle density. Instead, the peritumoral capillaries displayed three times as many endothelial surface-connected vesicles, a markedly thicker basal lamina, and significantly reduced extension of pericytic and glial investments. The kind and severity of the vascular modifications, compared with the slight edematous appearance of the nervous tissue, strengthen the hypothesis that peritumoral capillaries could be involved in the edema resolution process.
The woodchuck as an animal model for pathogenesis and therapy of chronic hepatitis B virus infection (2007)

This review describes the woodchuck and the woodchuck hepatitis virus (WHV) as an animal model for pathogenesis and therapy of chronic hepatitis B virus (HBV) infection and disease in humans. The establishment of woodchuck breeding colonies, and use of laboratory-reared woodchucks infected with defined WHV inocula, have enhanced our understanding of the virology and immunology of HBV infection and disease pathogenesis, including major sequelae like chronic hepatitis and hepatocellular carcinoma. The role of persistent WHV infection and of viral load on the natural history of infection and disease progression has been firmly established along the way. More recently, the model has shed new light on the role of host immune responses in these natural processes, and on how the immune system of the chronic carrier can be manipulated therapeutically to reduce or delay serious disease sequelae through induction of the recovery phenotype. The woodchuck is an outbred species and is not well defined immunologically due to a limitation of available host markers. However, the recent development of several key host response assays for woodchucks provides experimental opportunities for further mechanistic studies of outcome predictors in neonatal- and adult-acquired infections. Understanding the virological and immunological mechanisms responsible for resolution of self-limited infection, and for the onset and maintenance of chronic infection, will greatly facilitate the development of successful strategies for the therapeutic eradication of established chronic HBV infection. Likewise, the results of drug efficacy and toxicity studies in the chronic carrier woodchucks are predictive for responses of patients chronically infected with HBV. Therefore, chronic WHV carrier woodchucks provide a well-characterized mammalian model for preclinical evaluation of the safety and efficacy of drug candidates, experimental therapeutic vaccines, and immunomodulators for the treatment and prevention of HBV disease sequelae.
A comparative bioinformatic analysis of C9orf72 (2018)

<i>C9orf72</i> is associated with frontotemporal dementia (FTD) and Amyotrophic Lateral Sclerosis (ALS), both of which are devastating neurodegenerative diseases. Findings suggest that an expanded hexanucleotide repeat in the non-coding region of the <i>C9orf72</i> gene is the most common cause of familial FTD and ALS. Despite considerable efforts being made towards discerning the possible disease-causing mechanism/s of this repeat expansion mutation, the biological function of <i>C9orf72</i> remains unclear. Here, we present the first comprehensive genomic study on <i>C9orf72</i> gene. Analysis of the genomic level organization of <i>C9orf72</i> across select species revealed architectural similarity of syntenic regions between human and mouse but a lack of conservation of the repeat-harboring intron 1 sequence. Information generated in this study provides a broad genomic perspective of <i>C9orf72</i> which would form a basis for subsequent experimental approaches and facilitate future mechanistic and functional studies on this gene.
Comprehensive Model for Humidity Testing Correlation (1986)

This paper reviews all published life in humidity conditions vs life at 85C/85% RH for epoxy packages; 61 data points are used. An acceleration formula is described which provides direct extrapolation from test results in autoclave tests at up to at least 140C to low-humidity down to below 30XRH. This formula compares favorably with previously-published formulae. The possible effect of the Tg of the epoxy is recognized, and other high-temperature and low-humidity effects are disclosed. Recommendat ions are made for future tests, replacing 1000 hours at 85C/85%RH with a 20-hour test at 140C/100%RH, to reduce test time and increase test usefulness.
Making structures for cell engineering (2004)

This is a mainly historical account of the events, methods and artifacts arising from my collaboration with Adam Curtis over the past twenty years to make exercise grounds for biological cells. Initially the structures were made in fused silica by photo-lithography and dry etching. The need to make micron-sized features in biodegradable polymers, led to the development of embossing techniques. Some cells response to grooves only a few tens of nanometers deep--this led to a desire to find the response of cells to features of nanometric size overall. Regular arrays of such features were made using electron beam lithography for definition of the pattern. Improvements were made in the lithographic techniques to allow arrays to be defined over areas bigger than 1 cm2. Structures with microelectrodes arranged inside guiding grooves to allow the formation of sparse predetermined networks of neurons were made. It is concluded that the creation of pattern, as in vivo, in assemblies of regrown cells in scaffolds may well be necessary in advanced cell engineering applications.
Molecular typing for the MHC with PCR-SSP. (1999)

Sequence-specific amplification (SSP) is simply a form of polymerase chain reaction (PCR) which involves designing one or both primers so that they will or will not allow amplification (the 3'-mismatch principle). Its origins are probably legion, i.e. many people probably thought of it at the same time. For example, in 1988 a group from Guy's Hospital, London, described a form of SSP for HLA-DR4 detection and in the same year a group from Upjohn described its use at the American Society of Histocompatibility and Immunogenetics (ASHI). Both are published in abstract form (British Society of Rheumatology and ASHI). The 3'-mismatch principle can be used to identify virtually any single nucleotide point mutation (SNP) within one or two PCR-SSP reactions and the first peer-reviewed statements of this came in 1989 (1, 2). Thus, although the use of SSP probably began around 1990, it was 5 years before its popularity erupted, mainly due to the work of Olerup & Zetterquist (3, 4), who defined its potential for solid organ transplantation. It is now the method of choice for high resolution HLA typing in many laboratories. In addition, over a thousand applications for genes outside the MHC are in the literature.
Cyclosporin synthetase. The most complex peptide synthesizing multienzyme polypeptide so far described. (1990)

Cyclosporin A and its homologues are synthesized by a single multifunctional enzyme from their precursor amino acids. Cyclosporin synthetase is a polypeptide chain with a molecular mass of approximately 800 kDa. In 3% polyacrylamide-sodium dodecyl sulfate gels it shows a single band of approximately 650 kDa, which appears to not be glycosylated. The enzyme could be purified to near-homogeneity in five steps. A 72-fold purification was obtained. All constitutive amino acids of cyclosporins are activated as thioesters via aminoadenylation by the same enzyme. Then N-methylation of the thioester-bound amino acids which are present in methylated form in the cyclosporin molecule takes place, whereby S-adenosyl-L-methionine serves as the methyl group donor. Methyltransferase activity is an integral entity of the enzyme; this could be shown by a photoaffinity labeling method. 4'-Phosphopantetheine is a prosthetic group of cyclosporin synthetase similar to other peptide and depsipeptide synthetases. Cyclosporin synthetase shows cross-reactions with monoclonal antibodies directed against enniatin synthetase.
Determination of stereochemistry stability coefficients of amino acid side‐chains in an amphipathic α‐helix (2002)

We describe here a systematic study to determine the effect on secondary structure of d-amino acid substitutions in the nonpolar face of an amphipathic alpha-helical peptide. The helix-destabilizing ability of 19 d-amino acid residues in an amphipathic alpha-helical model peptide was evaluated by reversed-phase HPLC and CD spectroscopy. l-Amino acid and d-amino acid residues show a wide range of helix-destabilizing effects relative to Gly, as evidenced in melting temperatures (DeltaTm) ranging from -8.5 degrees C to 30.5 degrees C for the l-amino acids and -9.5 degrees C to 9.0 degrees C for the d-amino acids. Helix stereochemistry stability coefficients defined as the difference in Tm values for the l- and d-amino acid substitutions [(DeltaTm' = TmL and TmD)] ranging from 1 degrees C to 34.5 degrees C. HPLC retention times [DeltatR(XL-XD)] also had values ranging from -0.52 to 7.31 min at pH 7.0. The helix-destabilizing ability of a specific d-amino acid is highly dependent on its side-chain, with no clear relationship to the helical propensity of its corresponding l-enantiomers. In both CD and reversed-phase HPLC studies, d-amino acids with beta-branched side-chains destabilize alpha-helical structure to the greatest extent. A series of helix stability coefficients was subsequently determined, which should prove valuable both for protein structure-activity studies and de novo design of novel biologically active peptides.
Sutureless nerve repair at the fascicular level using a nerve coupler. (1989)

Peripheral nerves are transected in many traumatic injuries of the extremities. Satisfactory functional regeneration of such nerves often fails to occur after repair with sutures. Possible reasons for these failures include poor alignment of nerves or fascicles, intrusion of scar tissue into the nerve junction, and outgrowth of nerve tissue from the repair site. This animal study describes an experimental method of sutureless, monofascicular peripheral nerve repair using a resorbable nerve coupler in the rat model. The first version of this coupler shows approximately equal performance to suture repair. Histology and electrophysiology assessments after regeneration showed that the polyglycolic acid (PGA) tube repairs were functionally equal to monofascicular suture junctions as well as being quicker and simpler to perform. Modified coupler designs based on this and other work show greater promise. Collateral studies are using similar versions of the nerve coupler as a vehicle for the insertion of chemical and neuro-electronic factors that may enhance nerve regeneration.