gebhart/patrepeval huggingface dataset:
Effect of human fibroblast‐derived dermis on expansion of tissue from venous leg ulcers (2003)

Novel approaches to healing of chronic wounds, such as venous leg ulcers, include the use of tissue-engineered skin substitutes, e.g., human fibroblast-derived dermis. The exact mechanisms of action of these products and their effects on wound healing at a cellular level are yet to be fully defined. The aim of our study was to evaluate the potential effects of human fibroblast-derived dermis on the healing of chronic wounds using an experimental model. We used a tissue expansion model to examine the effect of human fibroblast-derived dermis on the growth of human tissue biopsied from venous leg ulcers. Further characterization of the cytokine profile produced by human fibroblast-derived dermis in culture was performed using enzyme-linked immunosorbent assay techniques. Addition of medium conditioned with human fibroblast-derived dermis significantly increased the outgrowth of cells from venous leg ulcer biopsies (p = 0.001). We detected bioactive levels of hepatocyte growth factor/scatter factor and interleukin-8 in media conditioned with human fibroblast-derived dermis. Therefore, conditioned media from human fibroblast-derived dermis enhances ex vivo expansion of tissue taken from chronic venous leg ulcers, and contains potent angiogenic factors. These experimental findings may explain the enhanced healing seen with clinical applications of human fibroblast-derived dermis on chronic wounds.
Structural Rearrangements Underlying K + -Channel Activation Gating (1999)

The intramembrane molecular events underlying activation gating in the Streptomyces K+ channel were investigated by site-directed spin-labeling methods and electron paramagnetic resonance spectroscopy. A comparison of the closed and open conformations of the channel revealed periodic changes in spin-label mobility and intersubunit spin-spin interaction consistent with rigid-body movements of the two transmembrane helices TM1 and TM2. These changes involve translations and counterclockwise rotations of both helices relative to the center of symmetry of the channel. The movement of TM2 increases the diameter of the permeation pathway along the point of convergence of the four subunits, thus opening the pore. Although the extracellular residues flanking the selectivity filter remained immobile during gating, small movements were detected at the C-terminal end of the pore helix, with possible implications to the gating mechanism.
Versuche zur Herstellung menschlicher monoklonaler Antikörper gegen Melanome unter Verwendung zervikaler Lymphknoten (1987)

Due to their specificity, constant properties and virtually unlimited supply monoclonal antibodies have given an important stimulus to almost every field of biomedical research within the last 10 years. The generation of mouse monoclonal antibodies includes immunisation of mice followed by fusion of mice spleen cells with a murine myeloma cell line. With this procedure hybridomas secreting monoclonal antibodies of a predefined specificity can be obtained. For three major reasons we worked on the establishment of human hybridomas secreting specific antibodies: human antibodies are less immunogenic when used for diagnostic or therapeutic purposes, only human monoclonal antibodies allow the analyses of the human B cell repertoire, there is evidence that human monoclonal antibodies recognise epitopes different from those seen by murine monoclonal antibodies. Therefore, we set out to generate human B cell hybridomas by cell fusion using the human lymphoblastoid B cell line Wi-L2-729 HF2 and lymphocytes from melanoma patients. The lymphocytes were isolated from tumour-draining cervical lymph nodes, stimulated with pokeweed mitogens plus the autologous tumour cells in an enriched tissue culture medium and fused in the presence of polyethylene glycol. Supernatants of hybridomas were screened in a single cell immunosorbent assay with either autologous melanoma cells or established melanoma cell lines fixed to the bottom of Terasaki plates or on cytospin preparations of these cells using the immunoperoxidase staining procedure. We could demonstrate that the tumour draining lymph nodes of these melanoma patients contained B lymphocytes capable of producing antibodies reacting with the tumour cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Impact of choice of kinetic model for the determination of transcutaneous FITC‐sinistrin clearance in rats with streptozotocin‐induced type 1 diabetes (2020)

Transcutaneous assessment of fluorescein isothiocyanate (FITC)-sinistrin clearance using an optical device was recently validated for determination of glomerular filtration rate (GFR) in conscious animals. In the current study, we compared four available kinetic models for calculating FITC-sinistrin clearance, to provide further insight into whether the choice of model might influence findings generated using this device. Specifically, we calculated the excretion half-life of FITC-sinistrin (minutes), rate constant (minute<sup>-1</sup> ) and GFR indexed to bodyweight in control rats and rats with streptozotocin-induced diabetes across a 4-week experimental period using standard one-compartment (1-COM), two-compartment (2-COM) and three-compartment (3-COM) kinetic models (1-COM), and a three-compartment kinetic model with baseline correction (3-COMB). Glomerular hyperfiltration was detected in STZ-induced diabetic rats with the 2-COM or 3-COMB at day 14 and with the 3-COM at day 3 and 14 after induction of diabetes, but not at any time point using the 1-COM. From a theoretical perspective, we reasoned that the 3-COMB model provides a better estimate of t<sub>1/2</sub> than the other models. Linear regression analysis of data generated using the 3-COMB showed a significant relationship between blood glucose and calculated GFR at the day 14 (P = .004) and day 28 (P = .01) time points, and a strong tendency for a relationship at the day 3 time point (P = .06). We conclude that hyperfiltration is an early and sustained characteristic of STZ-induced diabetes in rats. Furthermore, we propose that the 3-COMB model provides the most valid t<sub>1/2</sub> for estimation of GFR via transcutaneous detection of FITC-sinistrin clearance.
Inverse CVD: A Novel Synthetic Approach to Metallized Polymeric Films (1999)

Highly reflective and conductive silver surfaces on flexible polyimide films have been achieved by a novel single-stage self-metallizing procedure that utilizes similar chemistry to that involved in CVD. The film is cast as a silver(I)-doped poly(amic acid) solution. Thermal curing leads to cycloimidization of the polyimide precursor with concomitant silver(I) reduction. The result is a reflective and conductive surface approaching that of the native metal, while the film retains the essential mechanical and thermal characteristics of the parent film.
The osteogenic response to distant skeletal injury. (1990)

We tested the hypothesis that when one bone of the skeleton is injured, others experience an osteogenic response. Although similar or related phenomena have been observed previously, the purposes of the study were to determine if this response was reproducible, to characterize it in terms of its magnitude and duration, and to show how it is related to the type of injury sustained. To obtain this information, a model was used in which an intramedullary nail was implanted in the femur and a standard closed fracture was subsequently produced. The osteogenic response was measured by histomorphometry. Eight-four nine-week-old male Sprague-Dawley rats were divided into seven groups of twelve animals each. Groups I and II consisted of control animals in which no injury was produced. In Group-III rats, cortical drilling of the intercondylar notch and piriformis fossa of the right femur was performed, without intramedullary nailing. In Groups IV through VII, half of each group received intramedullary nails only, and in the other half intramedullary nailing was done and a closed transverse diaphyseal fracture was produced. With two different fluorochrome labels, rates of mineral apposition were measured in the left and right tibiae of all animals. The labeling periods differed in each group and were designed to determine when the peak response occurred, how long it lasted, and whether aging during the course of the experiment affected the response.(ABSTRACT TRUNCATED AT 250 WORDS)
Improved Exercise Capacity and Ischemia 6 and 12 Months After Transendocardial Injection of Autologous Bone Marrow Mononuclear Cells for Ischemic Cardiomyopathy (2004)

The 6- and 12-month follow-up data in this study suggest that transendocardial injection of ABMMNCs in patients with end-stage ischemic heart disease may produce a durable therapeutic effect and improve myocardial perfusion and exercise capacity.
Interleukin-10 Suppresses Proliferation and Remodeling of Extracellular Matrix of Cultured Human Skin Fibroblasts (2004)

When we previously examined the participation of local expression of interleukin-10 (IL-10) and tumor necrosis factor-alpha (TNFalpha) in wound healing of an intestinal anastomosis under septic conditions in mice, we found that IL-10 and TNFalpha expressions were markedly enhanced around the anastomosis and that wound healing was impaired in this animal model. The purpose of the present study was to investigate the combined effect of IL-10 on proliferation and remodeling of the extracellular matrix (ECM) of cultured human skin fibroblasts. Human skin fibroblasts were cultured for 48 h with IL-10 and/or TNFalpha at various concentrations, then the proliferation rates were determined using the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay. The concentration of transforming growth factor-beta1 (TGFbeta1) in cell culture supernatants was measured by enzyme-linked immunosorbent assay, and type I collagen protein and matrix metalloproteinase-I (MMP-I) were detected by indirect immunofluorescence in cultured cells incubated for 48 h with 10 ng/ml of IL-10 and/or 10 ng/ml of TNFalpha. IL-10 itself had no effect on fibroblast proliferation, but reduced TNFalpha-induced fibroblast proliferation. The concentration of TGFbeta1 in cell culture supernatants was significantly lower in the presence of TNFalpha and IL-10 than in the presence of TNFalpha alone. Immunolabeling of fibroblasts for type I collagen protein was decreased in cells incubated with IL-10 and/or TNFalpha compared to controls. MMP-I immunolabeling was increased in cells incubated with IL-10, IL-10 and TNFalpha compared to control and cells incubated with TNFalpha. It is suggested that IL-10 is an inhibitory factor for the remodeling of the ECM during wound healing.
Somatic Mutations in RET Exons 12 and 15 in Sporadic Medullary Thyroid Carcinomas: Different Spectrum of Mutations in Sporadic Type from Hereditary Type (1999)

Germline mutations in the RET proto-oncogene are responsible for multiple endocrine neoplasia type 2 (MEN 2A and 2B) and familial medullary thyroid carcinoma (FMTC). Point mutations or in-frame deletions of exons 10, 11, 13, 14 and 16 are associated with sporadic medullary thyroid carcinoma (MTC). To understand further the role of the RET gene in sporadic MTC, we examined mutations in exons 12 and 15 of RET in patients with sporadic MTC. DNAs were extracted from 39 formalin-fixed tumor tissues and corresponding normal thyroid tissues or peripheral blood leukocytes. DNA sequencing was used to identify mutations in exons 12 and 15 of RET. In this study, one novel somatic mutation was found in exon 12 and five novel mutations or deletions were found in exon 15. Of the patients with mutations, one had an in-frame 12-bp deletion (nt. 2625-2636), one had point mutations in both codons 884 and 908, and the remaining three had point mutations in codons 748, 876 and 901, respectively. Together with our previous identification of somatic mutations in exons 10, 11, 13, 14 and 16, somatic alterations were found in 10 out of 39 (25.6%) sporadic MTCs. There was no association of RET gene mutations with tumor recurrence or prognosis. These results suggest that mutations occur frequently in the RET coding region in addition to the previously reported mutation hot spots, and there is a different spectrum of mutations between sporadic and hereditary MTC.
Targeted disruption of the Epm2a gene causes formation of Lafora inclusion bodies, neurodegeneration, ataxia, myoclonus epilepsy and impaired behavioral response in mice (2002)

Mutations in the EPM2A gene encoding a dual-specificity phosphatase (laforin) cause Lafora disease (LD), a progressive and invariably fatal epilepsy with periodic acid-Schiff-positive (PAS+) cytoplasmic inclusions (Lafora bodies) in the central nervous system. To study the pathology of LD and the functions of laforin, we disrupted the Epm2a gene in mice. At two months of age, homozygous null mutants developed widespread degeneration of neurons, most of which occurred in the absence of Lafora bodies. Dying neurons characteristically exhibit swelling in the endoplasmic reticulum, Golgi networks and mitochondria in the absence of apoptotic bodies or fragmentation of DNA. As Lafora bodies become more prominent at 4-12 months, organelles and nuclei are disrupted. The Lafora bodies, present both in neuronal and non-neural tissues, are positive for ubiquitin and advanced glycation end-products only in neurons, suggesting different pathological consequence for Lafora inclusions in neuronal tissues. Neuronal degeneration and Lafora inclusion bodies predate the onset of impaired behavioral responses, ataxia, spontaneous myoclonic seizures and EEG epileptiform activity. Our results suggest that LD is a primary neurodegenerative disorder that may utilize a non-apoptotic mechanism of cell death.
MHC matching improves engraftment of iPSC-derived neurons in non-human primates (2017)

The banking of human leukocyte antigen (HLA)-homozygous-induced pluripotent stem cells (iPSCs) is considered a future clinical strategy for HLA-matched cell transplantation to reduce immunological graft rejection. Here we show the efficacy of major histocompatibility complex (MHC)-matched allogeneic neural cell grafting in the brain, which is considered a less immune-responsive tissue, using iPSCs derived from an MHC homozygous cynomolgus macaque. Positron emission tomography imaging reveals neuroinflammation associated with an immune response against MHC-mismatched grafted cells. Immunohistological analyses reveal that MHC-matching reduces the immune response by suppressing the accumulation of microglia (Iba-1+) and lymphocytes (CD45+) into the grafts. Consequently, MHC-matching increases the survival of grafted dopamine neurons (tyrosine hydroxylase: TH+). The effect of an immunosuppressant, Tacrolimus, is also confirmed in the same experimental setting. Our results demonstrate the rationale for MHC-matching in neural cell grafting to the brain and its feasibility in a clinical setting.Major histocompatibility complex (MHC) matching improves graft survival rates after organ transplantation. Here the authors show that in macaques, MHC-matched iPSC-derived neurons provide better engraftment in the brain, with a lower immune response and higher survival of the transplanted neurons.
Cholesterol-fed and casein-fed rabbit models of atherosclerosis. Part 1: Differing lesion area and volume despite equal plasma cholesterol levels. (1994)

One-month-old male New Zealand White rabbits were fed either a cholesterol-free casein diet (CAS; n = 10); low-level cholesterol-supplemented (0.125% to 0.5% by weight) chow (CH; n = 10); or standard laboratory rabbit chow (n = 3) for 24 weeks, during which total plasma cholesterol (TPC) levels were matched for the two experimental groups (TPCCAS = 475 +/- 39 mg/dL; TPCCH = 515 +/- 70 mg/dL). The percentage of cholesterol partitioned into each of the lipoprotein fractions except high-density lipoprotein (HDL) was significantly different for the experimental groups: casein-fed rabbits had a primarily low-density lipoprotein (LDL) hypercholesterolemia while cholesterol-fed rabbits had approximately equal levels of very-low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), and LDL cholesterol. Despite matched TPC, lesions in CH animals covered twice the luminal surface area (as detected by oil red O staining; P < .05) and had three times the total volume compared with lesions in the CAS group (P < .05). Lesion volume was positively correlated with TPC and IDL and LDL cholesterol for the CAS group and with TPC and IDL cholesterol for the CH group. When the experimental groups were combined, TPC and VLDL and IDL cholesterol were positively correlated with the lesion volume. Probability of occurrence maps revealed, however, that both groups were virtually identical with respect to the topographic distribution of lesions in the thoracic and abdominal aortas. The data suggested that the differential partitioning of cholesterol into the lipoprotein fractions seen in CAS and CH rabbits influenced lesion area and volume but not topographic distribution.
Advances in Sputum Analysis for Screening and Early Detection of Lung Cancer (2000)

These sputum tests provide an impetus to reconsider screening for lung cancer. Prospective trials are required to confirm test performance characteristics, and management and intervention strategies must be developed that are appropriate to the stage at which lung cancer is diagnosed.
Design and surface characteristics of 13 commercially available oral implant systems. (1993)

Thirteen commercially available oral implant systems were investigated with respect to design and surface topography. The implants were divided into four groups, depending on their different surface materials and treatments. Surface topography was measured with a measurement system for noncontact surface profilometry using confocal scanning microscopy. Results indicated that design, as well as surface topography, varied considerably between the different implant systems.
Investigation of Debio 025, a cyclophilin inhibitor, in the dystrophicmdxmouse, a model for Duchenne muscular dystrophy (2008)

Debio 025 partially improved the structure and the function of the dystrophic mouse muscle, suggesting that therapies targeting the mPTP may be helpful to DMD patients.
WikiPathways: Pathway Editing for the People (2008)

WikiPathways provides a collaborative platform for creating, updating, and sharing pathway diagrams and serves as an example of content curation by the biology community.
Acute mixed lineage leukemia in children: the experience of St Jude Children's Research Hospital (2009)

To characterize the biology and optimal therapy of acute mixed-lineage leukemia in children, we reviewed the pathologic and clinical features, including response to therapy, of 35 patients with mixed-lineage leukemia. The majority of cases (91%) had blasts cells that simultaneously expressed either T-lineage plus myeloid markers (T/myeloid, n = 20) or B-lineage plus myeloid markers (B/myeloid, n = 12). Overall survival rates for the B/myeloid and T/myeloid subgroups were not significantly different from each other or from the rate for acute myeloid leukemia (AML) but were inferior to the outcome in children with acute lymphoblastic leukemia (ALL). Patients who failed to achieve complete remission with AML-directed therapy could often be induced with a regimen of prednisone, vincristine, and L-asparaginase. Analysis of gene-expression patterns identified a subset of biphenotypic leukemias that did not cluster with T-cell ALL, B-progenitor ALL, or AML. We propose that treatment for biphenotypic leukemia begin with one course of AML-type induction therapy, with a provision for a switch to lymphoid-type induction therapy with a glucocorticoid, vincristine, and L-asparaginase if the patient responds poorly. We also suggest that hematopoietic stem cell transplantation is often not required for cure of these patients.
Animal models of spinal cord contusion injuries. (1999)

Use of these injury conditions provides reliable animal models for studies designed to evaluate potential therapeutic regimens for spinal cord injury.
Functional targeting of the MUC1 oncogene in human cancers (2009)

The MUC1 oncoprotein is aberrantly expressed at high levels in most human carcinomas and certain hematologic malignancies.1 Estimates are that, of the 1.4 million tumors diagnosed each year in the US, about 900,000 have overexpression of MUC1. MUC1 has thus become a highly attractive target for the development of new anti-cancer agents, including vaccines, antibodies and small molecules. However, there are presently no approved agents that target MUC1, in part because there has been limited information about how MUC1 contributes to the malignant phenotype. Indeed, MUC1 consists of two subunits, and the more recent focus of research on the MUC1 receptor subunit has provided new insights into (i) how MUC1 induces transformation and is of importance to human cancers, and (ii) how to target MUC1 function as an approach for anti-cancer treatment.
Involvement of a Lipoxygenase-Like Enzyme in Abscisic Acid Biosynthesis (1992)

Several lines of evidence indicate that abscisic acid (ABA) is derived from 9'-cis-neoxanthin or 9'-cis-violaxanthin with xanthoxin as an intermediate. (18)O-labeling experiments show incorporation primarily into the side chain carboxyl group of ABA, suggesting that oxidative cleavage occurs at the 11, 12 (11', 12') double bond of xanthophylls. Carbon monoxide, a strong inhibitor of heme-containing P-450 monooxygenases, did not inhibit ABA accumulation, suggesting that the oxygenase catalyzing the carotenoid cleavage step did not contain heme. This observation, plus the ability of lipoxygenase to make xanthoxin from violaxanthin, suggested that a lipoxygenase-like enzyme is involved in ABA biosynthesis. To test this idea, the ability of several soybean (Glycine max L.) lipoxygenase inhibitors (5,8,11-eicosatriynoic acid, 5,8,11,14-eicosatetraynoic acid, nordihydroguaiaretic acid, and naproxen) to inhibit stress-induced ABA accumulation in soybean cell culture and soybean seedlings was determined. All lipoxygenase inhibitors significantly inhibited ABA accumulation in response to stress. These results suggest that the in vivo oxidative cleavage reaction involved in ABA biosynthesis requires activity of a nonheme oxygenase having lipoxygenase-like properties.
Modified‐orientation log to assess hepatic encephalopathy (2012)

Modified-orientation log is a valid tool for assessing severity and is better than West-Haven criteria in predicting outcomes in hospitalised hepatic encephalopathy patients.