gebhart/patrepeval huggingface dataset:
Establishing humanized mice using stem cells: maximizing the potential (2008)

Studies on physiology and pathology as they relate to the immune system draw heavily upon rodent models. With the increasing impetus provided by initiatives in translational medicine, the demand for ever more sophisticated, 'humanized' murine models is greater than ever. However, the design and implementation of studies in such mice is far from trivial. Here we provide a technical perspective on the increasing interest in developing humanized mice. We give examples of primary data starting with the routine procurement of human donor material, through CD34(+) cell purification prior to engraftment to injection into immunocompromised mice. Our goal is to provide practical advice to the many investigators who may be commencing or considering such studies.
Pathological Ventricular Remodeling (2013)

Despite declines in heart failure morbidity and mortality with current therapies, rehospitalization rates remain distressingly high, substantially affecting individuals, society, and the economy. As a result, the need for new therapeutic advances and novel medical devices is urgent. Disease-related left ventricular remodeling is a complex process involving cardiac myocyte growth and death, vascular rarefaction, fibrosis, inflammation, and electrophysiological remodeling. Because these events are highly interrelated, targeting a single molecule or process may not be sufficient. Here, we review molecular and cellular mechanisms governing pathological ventricular remodeling.
Selective Accumulation of Related CD4+ T Cell Clones in the Synovial Fluid of Patients with Rheumatoid Arthritis (1998)

The role of T cells in the pathogenesis of rheumatoid arthritis (RA), especially in the perpetuation of advanced disease, remains unclear. Previous studies have focused on the TCR repertoire of synovial T cells in an attempt to determine whether the pattern of expression is characteristic of Ag-stimulated populations. However, the results of past studies have been conflicting. In the present work, we have undertaken an extensive analysis of the TCRs expressed by CD4+ T cells freshly isolated from synovial fluid of different joints and blood in three patients with established RA. Despite marked heterogeneity of synovial TCR expression, the results showed that 20 to 30% of the TCR beta-chain gene (TCRB) sequences found in one joint were also expressed in a second joint, but not in peripheral blood T cells of the same individual. Analysis of expressed TCRB complementarity-determining region 3 sequences showed the presence of multiple expanded clonal populations that were not predicted by quantitation of beta-chain variable region (Vbeta) expression by immunofluorescence staining. These studies also demonstrated sets of related, but different, complementarity-determining region 3 nucleotide sequences that encoded identical or highly homologous beta-chain amino acid sequences. Analysis of matching T cell clones derived from the joint by limiting dilution culture confirmed coexpression of highly homologous TCR alpha-chain gene (TCRA) and TCRB sequences. Together, these studies suggest that a significant proportion of synovial CD4+ T cells has been selected and expanded by conventional Ag(s) in this disease.
Characterization of Borrelia burgdorferi Strains in Lyme Arthritis (1998)

In the study presented, we investigated whether Lyme arthritis is associated with a particular Borrelia burgdorferi genospecies. Using the PCR technique, in 7/11 samples of synovial fluid of patients with Lyme arthritis a part of the ospA-gene was identified and the strains characterized by sequencing of the amplified DNA. Borrelia burgdorferi sensu stricto was found in 3 patients, B. garinii in 3, and B. afzelii in 1 patient. In conclusion, Lyme arthritis is caused by all 3 human pathogenetic genospecies which are actually known. For clinical practice PCR proved to be a rather insensitive diagnostic method, but may confirm the diagnosis of Lyme arthritis in doubtful cases.
Repeated growth and bubbling transfer of graphene with millimetre-size single-crystal grains using platinum (2012)

Large single-crystal graphene is highly desired and important for the applications of graphene in electronics, as grain boundaries between graphene grains markedly degrade its quality and properties. Here we report the growth of millimetre-sized hexagonal single-crystal graphene and graphene films joined from such grains on Pt by ambient-pressure chemical vapour deposition. We report a bubbling method to transfer these single graphene grains and graphene films to arbitrary substrate, which is nondestructive not only to graphene, but also to the Pt substrates. The Pt substrates can be repeatedly used for graphene growth. The graphene shows high crystal quality with the reported lowest wrinkle height of 0.8 nm and a carrier mobility of greater than 7,100 cm(2) V(-1) s(-1) under ambient conditions. The repeatable growth of graphene with large single-crystal grains on Pt and its nondestructive transfer may enable various applications.
Fractures of allografts. Frequency, treatment, and end-results. (1990)

One of the major complications of implantation of a massive frozen cadaveric allograft in the treatment of a tumor is fracture of the allograft. To determine the incidence, risk factors, appropriate management, and results of treatment of this complication, the records of the Orthopaedic Oncology Unit of the Massachusetts General Hospital were reviewed. Forty-three patients were identified in whom a tumor had been treated with an allograft that had subsequently fractured. The over-all incidence of fracture was almost 16 per cent. When the several risk factors (age and sex of the patient, stage and site of the lesion, and so on) for the forty-three patients who had a fracture were compared with those for the rest of the series, the only correlation was the incidence of non-union at the site of the host-donor junction, which was significantly higher in the patients who had a fracture. The mean time to fracture was 28.6 months after the operation. Three types of fractures occurred: Type I (two patients), rapid dissolution of the graft; Type II (twenty-two patients), fracture of the shaft, which was observed more frequently in male patients and which occurred a mean of 27.6 months after the operation; and Type III (nineteen patients), fragmentation of the joint, which usually occurred later (a mean of 31.6 months postoperatively) and was found more frequently in female patients.(ABSTRACT TRUNCATED AT 250 WORDS)
Platelet receptor-mediated factor X activation by factor IXa. High-affinity factor IXa receptors induced by factor VIII are deficient on platelets in Scott syndrome. (1989)

We have studied factor IXa binding and factor X activation with normal platelets and with platelets obtained from a patient with a bleeding disorder and an isolated deficiency of platelet procoagulant activity termed Scott syndrome. In the absence of factor VIIIa and factor X, normal, thrombin-treated platelets exposed 560 +/- 35 sites for factor IXa with a Kd of 2.75 +/- 0.27 mM, compared with 461 +/- 60 sites per patient platelet with Kd of 3.2 +/- 0.33 nM. The addition of factor VIIIa and factor X resulted in a decrease in the Kd for normal platelets to 0.68 nM but had no effect on the Kd for patient platelets. The concentrations of factor IXa required for half-maximal rates of factor X activation for normal (0.52 nM) and patient platelets (2.5 nM) were similar to those determined from equilibrium binding studies. Kinetic parameters for factor X activation by factor IXa showed that the Km and Kcat were identical for normal and patient platelets in the absence of factor VIIIa. In the presence of factor VIIIa, and kcat for patient platelets (163 min-1) was only 33% of that for normal platelets (491 min-1): This result can be explained by the difference in affinity for factor IXa between normal and patient platelets in the presence of factor VIIIa, suggesting impaired factor VIIIa binding to Scott syndrome platelets.
ENZYMES AND MOLECULAR MECHANISMS OF GENETIC RECOMBINATION (1992)

The Hippo pathway was initially discovered in Drosophila melanogaster as a key regulator of tissue growth. It is an evolutionarily conserved signaling cascade regulating numerous biological processes, including cell growth and fate decision, organ size ...Read More
A peripheric neuromodulation technique for curing detrusor overactivity: Stoller afferent neurostimulation (2005)

SANS is an easy and inexpensive therapeutic method with low morbidity in patients with an overactive bladder. Combination with a low-dose anticholinergic increases the success rate without causing any significant side-effects.
Correcting endogenous concentrations of testosterone influences bioequivalence and shows the superiority of TDS(R)-testosterone versus Androgel(R). (2009)

Different results obtained in the relative bioavailability between TDS-testosterone and Androgel for uncorrected data and corrected data, suggests that correcting endogenous concentrations is important for the proper determination of bioequivalent for endogenous compounds such as testosterone.
Proinflammatory cytokines tumor necrosis factor-α and interferon-γ alter tight junction structure and function in the rat parotid gland Par-C10 cell line (2008)

Sjögren's syndrome (SS) is an autoimmune disorder characterized by inflammation and dysfunction of salivary glands, resulting in impaired secretory function. The production of the proinflammatory cytokines tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) is elevated in exocrine glands of patients with SS, although little is known about the effects of these cytokines on salivary epithelial cell functions necessary for saliva secretion, including tight junction (TJ) integrity and the establishment of transepithelial ion gradients. The present study demonstrates that chronic exposure of polarized rat parotid gland (Par-C10) epithelial cell monolayers to TNF-alpha and IFN-gamma decreases transepithelial resistance (TER) and anion secretion, as measured by changes in short-circuit current (I(sc)) induced by carbachol, a muscarinic cholinergic receptor agonist, or UTP, a P2Y(2) nucleotide receptor agonist. In contrast, TNF-alpha and IFN-gamma had no effect on agonist-induced increases in the intracellular calcium concentration [Ca(2+)](i) in Par-C10 cells. Furthermore, treatment of Par-C10 cell monolayers with TNF-alpha and IFN-gamma increased paracellular permeability to normally impermeant proteins, altered cell and TJ morphology, and downregulated the expression of the TJ protein, claudin-1, but not other TJ proteins expressed in Par-C10 cells. The decreases in TER, agonist-induced transepithelial anion secretion, and claudin-1 expression caused by TNF-alpha, but not IFN-gamma, were reversible by incubation of Par-C10 cell monolayers with cytokine-free medium for 24 h, indicating that IFN-gamma causes irreversible inhibition of cellular activities associated with fluid secretion in salivary glands. Our results suggest that cytokine production is an important contributor to secretory dysfunction in SS by disrupting TJ integrity of salivary epithelium.
Mechanics of Respiration in Unanesthetized Guinea Pigs (1958)

A technique has been described by which tidal volume, intrapleural pressure and rate of flow of gas in and out of the respiratory system can be measured simultaneously in unanesthetized guinea pigs for periods of several hours. These data permit the calculation of the pulmonary flow-resistance and compliance for an experimental animal with normal reflex behavior. The values obtained on 200 normal and 20 tracheotomized animals for tidal volume, respiratory rate, minute volume, resistance and compliance are given.
Growth Kinetics, Nutrient Uptake, and Expression of the Alcaligenes eutrophus Poly(β‐hydroxybutyrate) Synthesis Pathway in Transgenic Maize Cell Suspension Cultures (1997)

Transgenic suspension cultures of Black Mexican Sweet maize (Zea mays L.) expressing the Alcaligenes eutrophus genes encoding enzymes of the pathway for biosynthesis of the biodegradable polymer poly(beta-hydroxybutyrate) (PHB) were established as a tool for investigating metabolic regulation of the PHB pathway in plant cells. Cultures were grown in a 2 L modified mammalian cell bioreactor and in shake flasks. Biomass doubling times for transgenic bioreactor cultures (3.42 +/- 0.76 days) were significantly higher than those for untransformed cultures (2.01 +/- 0.33 days). Transgenic expression of the bacterial enzymes beta-ketothiolase (0.140 units/mg protein) and acetoacetyl-CoA reductase (0.636 units/mg protein) was detected by enzyme assays and immunoblots. However, over the first 2 years of cultivation, reductase activity decreased to 0.120 units/mg proteins. Furthermore, the PHB synthase gene, although initially present, was not detectable after 1.5 years of cultivation in suspension culture. These facts suggest that transgenic expression of PHB pathway genes in plant cells may not be stable. A hydroxybutyrate derivative was detected via gas chromatography even after 4 years of cultivation. Although the method used to prepare samples for gas chromatography cannot directly distinguish among PHB polymer, hydroxybutyryl-CoA (HB-CoA), and hydroxybutyric acid, solvent washing experiments indicated that most or all of the signal was non-polymeric, presumably H-CoA. The synthesis of HB-CoA appeared to be linked to substrate growth limitation, with HB-CoA accumulation increasing dramatically and cell growth ceasing upon depletion of ammonium. This suggests that the PHB synthesis pathway in plants is subject to regulatory mechanisms similar to those in prokaryotic cells.
Familial infantile bilateral striatal necrosis (2002)

Familial infantile bilateral striatal necrosis was inherited as an autosomal recessive trait. Clinical features included developmental arrest, dysphagia, and choreoathetosis. Imaging and pathology showed atrophy and degeneration of the basal ganglia. Oral biotin may have benefited three children.
Effect of exogenous fatty acids with greater than 22 carbon atoms (very long chain fatty acids) on superoxide production by human neutrophils. (1994)

The effects of exogenous long chain fatty acids (LCFA) and very long chain fatty acids (VLCFA) on superoxide production by human neutrophils were compared. Superoxide production was greater and more rapid in response to arachidonic (20:4 (n-6)), eicosapentanoic (20:5 (n-3)), and docosahexanoic (22:6 (n-3)) acids than for triacontatetranoic (30:4 (n-6)), dotriacontatetranoic (32:4 (n-6)), and tetratriacontahexanoic (34:6 (n-3)) acids, although all of these fatty acids gave responses larger than FMLP. A similar decline in activity with increasing carbon chain length was observed for the monoenoic VLCFA (22:1 (n-9) to 34:1 (n-9)). 32:4 (n-6) did not affect responses to a maximally stimulatory concentration of 20:4 (n-6). However, the simultaneous addition of 20:4 (n-6) and 30:4 (n-6) gave additive responses if suboptimal dosages of 20:4 (n-6) were used. This suggests that the LCFA and VLCFA may use the same signal transduction systems. In addition, 30:4 (n-6) was only 10% as effective as was 20:4 (n-6) at gaining access to the organic solvent extractable cellular fraction. This figure correlated with the relative biologic potency of 20:4 (n-6) and 30:4 (n-6), suggesting that the extent of association with the cell may regulate the biologic activity of the fatty acids. The saturates, arachidic (20:0) and cerotic (26:0) acids, were either inactive or poor activators in all assay systems examined. The failure of 20:0 to induce superoxide production and the lower responses to 30:4 (n-6) and 34:6 (n-3) were not because of extracellular Ca2+, because the biologic potency of these fatty acids was not greatly enhanced by removing Ca2+ from the extracellular medium. In contrast, 20:4 (n-6)- and 22:6 (n-3)-induced superoxide production was markedly increased under Ca(2+)-free conditions.
Cytokines and Allergic Diseases: Clinical Aspects (1998)

In recent years there has been an explosive expansion of knowledge relating to a family of proteins involved in the intercellular communication network of the immune system. These substances, referred to as cytokines, are importantly involved in the highly regulated complex sequence of events of cellular interaction that comprise immune responses. Atopic diseases, which afflict 20-30% of the general population, are now considered to be associated with a set of abnormal genetically regulated immune responses to foreign antigens, i.e., allergens. The atopic individuals is characterized by the excessive production of IgE antibody to allergens after inhalation, ingestion, and surface contact. There are now recognized over 19 major classes of cytokines, which have been organized into the following categories according to their major functional activities: 1) Acute phase reactants, promoting and mediating natural immunity (e.g., IL-1, IL-6, TNF, interferons alpha and beta, and IL-8); 2) Cytokines that mediate cellular growth and differentiation (e.g., IL-7, IL-4, IL-2, IL-5, IL-10, IL-12, IL-13); 3) Cytokines that act as hematopoietic growth factors (IL-3, GMCSF, IL-9, IL-11, stem cell factor); 4) Chemokines (alpha and beta major groups, DTG, RANTES); and 5) Cytokines that exert lymphocyte regulatory activity (EG, IFN-gamma, TGF). Of particular importance to allergic disease is the recent recognition of the regulation of helper immune function by two lineages of T helper cells, i.e., Th1 and Th2, by these cytokines. The Th2 hypothesis of allergy (4) considers atopy as a Th2-driven hypersensitivity reaction to allergens of complex genetic and environmental origins, in which the Th1 lineage, normally driven by IL-2, TNF, and IFN-gamma is deficient, and in which a predominant Th2 response is seen that is driven by IL-4, IL-13, IL-5, and IL-10. This knowledge is finding application in both the diagnosis and therapy of allergic diseases, through the measurement or use of cytokines, which may replace deficient quantities, or the use of anticytokines, which may neutralize elevated quantities of cytokines, events that collectively contribute to the immunologic imbalance characteristic of the allergic state. In the future, the application of cytokines will continue to find clinical application in allergic disease, and it behooves the clinical allergist-immunologist to keep abreast of the exciting new developments that are occurring in this field.
Nrf2, a multi‐organ protector? (2005)

NF-E2-related factor 2 (Nrf2) is a basic leucine zipper transcription factor that binds to the promoter sequence "antioxidant responsive element (ARE)" leading to coordinated up-regulation of ARE-driven detoxification and antioxidant genes. Since the expression of a wide array of antioxidant and detoxification genes are positively regulated by the ARE sequence, Nrf2 may serve as a master regulator of the ARE-driven cellular defense system against oxidative stress. In support of this, numerous studies have shown that Nrf2 protects many cell types and organ systems from a broad spectrum of toxic insults and disease pathogenesis. This Nrf2-conferred, multi-organ protection phenomenon raises an interesting question about how a single protein can protect many different organs from various toxic insults. A possible molecular mechanism explaining this phenomenon is that Nrf2 protects many different cell types by coordinately up-regulating classic ARE-driven genes as well as cell type-specific target genes that are required for the defense system of each cell type in its unique environment. This hypothesis is supported by microarray data indicating the protective role of Nrf2 is conveyed through both known ARE-driven genes and novel cell type-specific genes. The widespread nature of Nrf2 may have an important therapeutic potential, allowing prevention of carcinogenesis and neurodegenerative diseases.
MT1‐MMP: A key regulator of cell migration in tissue (2006)

Controlled cell migration is a fundamental and critical event in many physiological processes. However once control is lost, cell migration facilitates disease progression such as seen in cancer metastasis, atherosclerosis, and rheumatoid arthritis. One of the critical proteinases involved in cell migration is membrane-type 1 matrix metalloproteinase (MT1-MMP/MMP-14). MT1-MMP degrades extracellular matrix to make a path for cells to migrate, sheds cell surface molecules to give migratory signals, and activates ERK (extracellular signal-regulated protein kinase) enhancing cell migration. For MT1-MMP to promote cell migration, it needs to act in co-ordination with other cell migration machinery. Understanding such regulatory links may provide insights into the development of novel disease therapies.
CARRIER-MEDIATED TRANSPORT OF THYROID HORMONE INTO RAT HEPATOCYTES IS RATE-LIMITING IN TOTAL CELLULAR UPTAKE AND METABOLISM (1986)

We investigated if carrier-mediated transport into rat hepatocytes is rate-limiting in total cellular uptake and metabolism of thyroid hormone. Rat hepatocytes in primary monolayer culture were incubated under equilibrium conditions with tracer T4, T3 or rT3 in the absence or presence of inhibitors of thyroid hormone uptake, i.e., ouabain and ER-22, a monoclonal antibody against the rat hepatocyte plasma membrane. The results for all three iodothyronines show that inhibition of clearance from the medium during incubation is paralleled by a similar decrease in iodide production. This indicates that the decrease in metabolism of thyroid hormone is directly related to the inhibition of cellular uptake. These findings underline the potential importance of the plasma membrane in the regulation of thyroid hormone metabolism and, therefore, determination of expression of thyroid hormone activity.
Mouse Genome Editing Using the CRISPR/Cas System (2014)

The availability of techniques to create desired genetic mutations has enabled the laboratory mouse as an extensively used model organism in biomedical research including human genetics. A new addition to this existing technical repertoire is the CRISPR/Cas system. Specifically, this system allows editing of the mouse genome much more quickly than the previously used techniques, and, more importantly, multiple mutations can be created in a single experiment. Here we provide protocols for preparation of CRISPR/Cas reagents and microinjection into one-cell mouse embryos to create knockout or knock-in mouse models.
Antioxidative and steroid systems in neurological and psychiatric disorders (2005)

A large number of neurological and psychiatric diseases like Morbus Parkinson, amyotrophic lateral sclerosis, dementia, schizophrenia and probably also affective disorders show an enhanced production of reactive oxygen species. Moreover, alterations of antioxidative systems and beneficial effects of antioxidative substances including steroid compounds such as estrogens have been described in several of these diseases. This review focuses on alterations of antioxidative systems in the course of neurological diseases and psychiatric disorders and on the differential effects of steroids on these systems in the central nervous system. Moreover, a possible clinical relevance of alterations of circulating steroids and of steroid treatment under these conditions is discussed.