gebhart/patrepeval huggingface dataset:
Azithromycin in bronchiolitis obliterans complicating bone marrow transplantation: a preliminary study (2005)

Bronchiolitis obliterans (BO) is a serious noninfectious pulmonary complication following allogeneic bone marrow transplantation (BMT). Azithromycin, a macrolide antibiotic, may have a beneficial effect in BO through its anti-inflammatory effect. The aim of the current study was to investigate the potential effect of azithromycin on pulmonary function tests (PFTs) in BO complicating BMT. PFTs of 153 post-BMT patients were followed; eight patients out of 153 (12%) developed obstructive airway disease on their PFTs, along with characteristic findings of BO on high-resolution computed tomography of the chest. These patients were given azithromycin 500 mg q.d. for 3 days, followed by 250 mg three times a week for 12 weeks. Clinically significant improvements were achieved both in forced vital capacity, where the mean (95% confidence interval) increase reported was 410 mL (0.16-0.65), which was an average improvement of 21.57%, and in the forced expiratory volume in one second, where the mean increase noticed was 280 mL (0.10-0.44), which was an average improvement of 20.58%. In conclusion, the potential role of azithromycin in the treatment of bronchiolitis obliterans is intriguing and it warrants further testing.
The Role of Anticoagulation in Cancer Patients: Facts and Figures (2006)

Thromboembolic events contribute significantly to the morbidity and mortality in cancer. Effective and safe anticoagulation - mainstay in prevention and treatment of thrombosis - remains very challenging clinical task in oncology patients - population of high rate of treatment failure, bleeding complications and thromboembolic events recurrences. Prospective randomized clinical studies have documented that with advent of low molecular weight heparins new possibilities for thrombosis treatment and long-term prevention with more convenient and safe anticoagulation have emerged. Considerable advances have been achieved at present time in our understanding of the pathobiology of thrombogenesis in human malignancies, particularly of the interactions between coagulation cascade reactions and processes of tumor growth and dissemination. This builds up a new challenge for modern oncology - appreciation of the hypothesis of anti-malignant effects of anticoagulants, which could influence the outcome of human cancer. Antineoplastic effects of antithrombotic drugs have been reported in various experimental models. Heparins have been the most extensively studied and have been shown to reduce the primary tumour growth and its metastatic spread. Joint evidence from fundamental research and from several randomized clinical trials, observing beneficial impact of low molecular weight heparins therapy on cancer patients survival, dictate the need for further scientific steps to confirm biological effects of heparins in human malignancies. The evidence is started to accumulate, that clinically approved heparins have different abilities to influence some processes of metastasis spread. The experimental work towards development of heparin derivates with low anticoagulant activity, but with potential inhibitory effects on tumor cells migration is in progress.
Upregulation of PD-1 Expression on Circulating and Intrahepatic Hepatitis C Virus-Specific CD8+T Cells Associated with Reversible Immune Dysfunction (2007)

ABSTRACT Infection with hepatitis C virus (HCV) is associated with persistence in the majority of individuals. We demonstrate here that the inhibitory molecule programmed death-1 (PD-1) is significantly upregulated on total and HCV-specific CD8 + cytotoxic T lymphocytes (CTLs) in the peripheral blood and livers of patients with chronic infection compared to subjects with spontaneous HCV resolution, patients with nonviral liver disease, and normal controls. PD-1 expression on cytomegalovirus-specific CTLs also varies according to HCV status and is highest in patients with chronic infection. HCV-specific CTLs that are PD-1 high express higher levels of the senescence marker CD57 than PD-1 low CTLs, and CD57 expression is greater in chronic than in resolved infection. In vitro blockade of PD-1 by monoclonal antibodies specific to its ligands (PD-L1 and PD-L2) results in restoration of functional competence (proliferation and gamma interferon and interleukin-2 secretion) of HCV-specific CTLs, including those residing in the liver. This reversal of CTL exhaustion is evident even in individuals who lack HCV-specific CD4 + T-cell help. Our data indicate that the PD-1/PD-L pathway is critical in persistent HCV infection in humans and represents a potential novel target for restoring function of exhausted HCV-specific CTLs.
Millisecond switching in solid state electrochromic polymer devices fabricated from ionic self-assembled multilayers (2008)

The electrochromic switching times of solid state conducting polymer devices fabricated by the ionic self-assembled multilayer method has been investigated. The devices were composed of bilayers of poly(3,4-ethylenedioxythiophene): poly(styrenesulfonate) and poly(allylamine hydrochloride) on indium tin oxide substrates. Devices fabricated from 40 bilayer thick films have coloration and decolaration switching times of 31 and 6ms, respectively, with low applied voltage (1.4V) for an active area of 0.6cm2. The switching times have been shown to decrease with the active area of the electrochromic device suggesting that even faster electrochromic switching times are possible for devices with smaller areas.
Expression of cancer testis antigens in head and neck squamous cell carcinomas (2006)

We conclude that the tumor-specific antigen genes are expressed in variable frequencies and intensities in the primary lesions of head and neck squamous cell carcinomas and in their metastases, with expression of the PRAME gene being always present in the metastastatic lymph nodes. In primary lesions, gene expression correlated with smoking habit and with advanced tumors with a higher malignant potential, with the frequent expression of two or more of these genes.
Aerosol Infection of BALB/c Mice with Brucella melitensis and Brucella abortus and Protective Efficacy against Aerosol Challenge (2007)

Brucellosis is a zoonotic disease with a worldwide distribution that can be transmitted via intentional or accidental aerosol exposure. In order to engineer superior vaccine strains against Brucella species for use in animals as well as in humans, the possibility of challenge infection via aerosol needs to be considered to properly evaluate vaccine efficacy. In this study, we assessed the use of an aerosol chamber to infect deep lung tissue of mice to elicit systemic infections with either Brucella abortus or B. melitensis at various doses. The results reveal that B. abortus causes a chronic infection of lung tissue in BALB/c mice and peripheral organs at low doses. In contrast, B. melitensis infection diminishes more rapidly, and higher infectious doses are required to obtain infection rates in animals similar to those of B. abortus. Whether this difference translates to severity of human infection remains to be elucidated. Despite these differences, unmarked deletion mutants BADeltaasp24 and BMDeltaasp24 consistently confer superior protection to mice against homologous and heterologous aerosol challenge infection and should be considered viable candidates as vaccine strains against brucellosis.
Successful pregnancy and delivery in a patient with adult GH deficiency: role of GH replacement therapy (2010)

Adult growth hormone deficiency (AGHD) is a recently recognized endocrine disorder characterized by low peak GH levels during provocative tests. The AGHD has a negative impact on bone mineral density, skeletal muscle strength, physical capacity and psychosocial well-being. Furthermore, the girls with GHD have delayed pubertal development, and in adulthood present a condition of subfertility. Treatment for AGHD with GH replacement therapy has been officially approved since 2006 in Japan. The patient was diagnosed as pituitary dwarfism at age 9. She was treated with GH replacement therapy since diagnosis until her height reached 155cm at age 15. When she was 24 years old, she suffered from clinical symptoms relating to GH deficiency, and she visited our hospital for reintroduction of the therapy to alleviate these clinical symptoms. She has been treated with the replacement therapy since then. The patient's dysmenorrhea improved. And she was found to be 8 weeks pregnant at age 28 years 7 months. We immediately ceased replacement therapy and carefully observed the patient, because it is not indicated for female patient with pregnancy. She delivered a healthy girl at 40 weeks of pregnancy, no recognizable side-effects were observed in either mother or baby. To our knowledge, there are no other reports of a Japanese patient becoming pregnant during GH replacement therapy, and few cases have been reported in other countries. It remains uncertain whether the therapy is safe and essential for fetal development, fertility, and continuation of pregnancy in AGHD subjects.
Compact and fast read-out for wavelength-encoded biosensors (2010)

Many established and recently-introduced optical biosensor concepts rely on the detection of a small wavelength change in response to change of temperature, adhesion of bio-particles, strain, or chemical environment. Special coatings are used to sensitize them to specifically bound molecules (e.g., biomarkers). We describe a compact and fast wavelength monitor that can resolve sub-pm wavelength changes. The unit was demonstrated by reading out a FBG sensor and can resolve wavelength changes as small as 50fm with a bandwidth of more than 100Hz.
Correction: Drug Repositioning by Kernel-Based Integration of Molecular Structure, Molecular Activity, and Phenotype Data (2013)

Computational inference of novel therapeutic values for existing drugs, i.e., drug repositioning, offers the great prospect for faster and low-risk drug development. Previous researches have indicated that chemical structures, target proteins, and side-effects could provide rich information in drug similarity assessment and further disease similarity. However, each single data source is important in its own way and data integration holds the great promise to reposition drug more accurately.
Skin cancer. Melanoma and other specific nonmelanoma skin cancers (1995)

The variations among incidence rates of melanoma by sex, subsite, race, geographic location, and time period support prevailing theories of a solar cause for most but not all cases of this disease. Although melanoma rates are rising overall, the disproportionate rise in the rate of diagnosis of in situ compared with invasive melanoma suggests that melanomas are being diagnosed earlier.
Endosialin/TEM-1/CD248 regulates pericyte proliferation through PDGF receptor signaling (2010)

Recent reports have described several cellular phenotypes that appear to be mediated by Endosialin/TEM-1/CD248 (TEM-1), including tubule formation on matrigel, migration and proliferation. It has been shown that siRNA knock-down of TEM-1 in primary human fibroblasts resulted in reduced proliferation. However, the downstream signaling events that mediate TEM-1 function(s) currently remain unknown. In this study, we demonstrate that TEM-1 mediates proliferation of primary human pericytes through a PDGF receptor signaling pathway. Normal pericytes expressing high levels of TEM-1 were able to proliferate, respond to PDGF-BB stimulation by phosphorylating both the PDGF receptor and the MAP kinase ERK-1/2, and induce the expression of the immediate early transcription factor c-Fos. However, when TEM-1 expression was knocked-down, PDGF-BB-induced proliferation, ERK-1/2 phosphorylation, and c-Fos expression were significantly impaired. Thus, our results provide evidence for a TEM-1-dependent signal pathway that controls proliferation of human pericytes and suggest targeting this pathway for future strategies aimed at mitigating tumor angiogenesis.
IgA:IgM and IgA:IgA hybrid hybridomas secrete heteropolymeric immunoglobulins that are polyvalent and bispecific. (1988)

Polyvalent bispecific antibodies were secreted by hybrid hybridoma cells when both parental clones expressed a naturally polymerizing immunoglobulin. Hybrid hybridomas made from IgA lambda 2 anti-trinitrophenyl (TNP) and IgA kappa anti-phosphocholine (PC) parental cells secreted polymeric IgA antibodies that bound both TNP and PC. Some of the TNP binding was dissociated from the PC binding under conditions of mild reduction and alkylation suggesting that the bispecific polymeric IgA contained disulfide-linked parental monomers as well as bispecific hybrid monomers. Hybrid hybridomas constructed from IgA lambda 2 anti-TNP and IgM kappa anti-ox erythrocyte parental cells secreted bispecific, polymeric immunoglobulin that contained mu-, alpha-, kappa-, and lambda 2-chains. The mu and kappa-chains dissociated from the alpha- and lambda 2-chains under conditions of mild reduction and alkylation, indicating that both parental monomers had been incorporated into the same polymeric immunoglobulin to form a heteropolymeric antibody molecule. Heterologous pairing of alpha and mu heavy chains in monomers was not detected. Hybrid hybridomas constructed from IgA lambda 2 and IgG3 lambda 2 or IgA lambda 2 and IgG1 kappa parents co-secreted both parental immunoglobulins, but the antibodies secreted by these clones did not form heteropolymers or exhibit heterologous heavy chain pairing. These findings establish that polyvalent, bispecific, polymeric immunoglobulin molecules can be produced by hybrid hybridomas when both parents express a naturally polymerizing class of heavy chain but not when only one parent does. Hybrid hybridomas that produce heteropolymeric immunoglobulins are sources of high avidity bispecific antibodies that may find a number of basic and practical applications. The hybridoma cells that produce these antibodies may provide useful tools for investigating the in situ determinants of immunoglobulin chain association and the regulation of antibody assembly and secretion.
Therapie der physikalischen Urtikaria: Antihistaminika und Alternativen (2001)

Wichtigste Voraussetzungen für eine erfolgreiche Behandlung der physikalen Urtikaria sind die exakte Diagnose des spezifischen Subtyps, eine gründliche Aufklärung des Patienten, damit er auslösende Reize möglichst meidet, und der Ausschluß von behandelbaren, möglicherweise die Symptomatik unterhaltenden anderen Krankheiten. Bei der Kälteurtikaria lohnt sich zudem bei mehr als der Hälfte der Patienten eine Behandlung mit Penizillin oder Tetrazyklinen, obwohl deren Wirkung unklar ist. Den meisten Patienten ist auch mit einer symptomatischen Behandlung mit Antihistaminika geholfen, evtl. in höherer Dosierung, dem Rest zumeist mit anderen Antiphlogistika. Bei ausgeprägter cholinergischer Urtikaria kann Cetirizin in Kombination mit Danazol hilfreich sein. Die schwer behandelbare verzögerte Druckurtikaria spricht gelegentlich auf Dapson oder Sulfasalazin an, diätetische Maßnahmen können aber auch Linderung bringen. Bei der Licht- und Kälteurtikaria kann eine kurzfristig anhaltende Toleranz induziert und bei der cholinergischen Urtikaria die Refraktärzeit gezielt genutzt werden. Mit diesen vielfachen therapeutischen Möglichkeiten gestaltet sich die Behandlung der physikalischen Urtikaria für Patient und Arzt zumeist gleichermaßen zufriedenstellend.
Towards automatic detection of point mutations: use of scintillating microplates in solid-phase minisequencing. (1994)

Simplification of molecular genetic techniques is one of the main features of large-scale clinical applications of mutation analysis. The solid-phase minisequencing method, which is based on single-nucleotide primer extension by a DNA polymerase on a solid support, is an easy way of detecting point mutations of previously known locations. Here the procedure was further simplified by the use of microplates made of scintillating plastics, a microplate format scintillation counter and an automatic microplate washer. DNA samples from patients with either a hereditary aspartylglucosaminidase (AGA) gene point mutation or an acquired N-ras gene mutation were analyzed by three different minisequencing detection procedures utilizing tritiated nucleotides. The new counting method with scintillating plates was compared to traditional liquid scintillation counting in scintillation vials or to another microplate format procedure, which requires addition of scintillation liquid. In all three methods, normal individuals, heterozygous carriers of the AGA mutation and homozygous patients could be unequivocally discriminated. The N-ras mutation in leukemic blasts could also be detected with high resolution. The coefficients of variation and reproducibility of the scintillating microplate method were almost identical to those of the traditional liquid scintillation assay, which was used as a reference method. The technical innovations adopted here for performing minisequencing assays reduce significantly the labor required without affecting the quality of the results.
Rapid and Precise Quantification of HIV-1 RNA in Plasma Using a Branched DNA Signal Amplification Assay (1995)

The level of human immunodeficiency virus type 1 (HIV-1) RNA in human plasma has been quantitated directly with use of a solid-phase nucleic acid hybridization assay, based on branched DNA (bDNA) signal amplification technology with chemiluminescent detection. Signal amplification is accomplished by the incorporation of sites for 1,755 alkaline phosphatase-labeled probes per genome of HIV-1, after successive hybridization of target-specific oligonucleotides and bDNA amplifier molecules. The assay is performed in microwells, much like an immunoassay, and is amenable to routine laboratory use. Reproducibility and specificity studies indicated that the bDNA method was precise and showed no reactivity with seronegative donors. HIV-1 RNA levels were quantitated for 348 seropositive specimens, with a detection rate of 83% for those specimens from patients with < 500 CD4+ T-cell counts. Plasma RNA levels were found to change with disease stage, and in response to antiviral therapy. Quantitation of HIV-1 RNA in the plasma of HIV-1-infected patients, with use of the bDNA assay, may be a useful method for monitoring HIV-1 disease progression and therapeutic response.
Runx1 is required for zebrafish blood and vessel development and expression of a human RUNX1-CBF2T1 transgene advances a model for studies of leukemogenesis (2002)

RUNX1/AML1/CBFA2 is essential for definitive hematopoiesis, and chromosomal translocations affecting RUNX1 are frequently involved in human leukemias. Consequently, the normal function of RUNX1 and its involvement in leukemogenesis remain subject to intensive research. To further elucidate the role of RUNX1 in hematopoiesis, we cloned the zebrafish ortholog (runx1) and analyzed its function using this model system. Zebrafish runx1 is expressed in hematopoietic and neuronal cells during early embryogenesis. runx1 expression in the lateral plate mesoderm co-localizes with the hematopoietic transcription factor scl, and expression of runx1 is markedly reduced in the zebrafish mutants spadetail and cloche. Transient expression of runx1 in cloche embryos resulted in partial rescue of the hematopoietic defect. Depletion of Runx1 with antisense morpholino oligonucleotides abrogated the development of both blood and vessels, as demonstrated by loss of circulation, incomplete development of vasculature and the accumulation of immature hematopoietic precursors. The block in definitive hematopoiesis is similar to that observed in Runx1 knockout mice, implying that zebrafish Runx1 has a function equivalent to that in mammals. Our data suggest that zebrafish Runx1 functions in both blood and vessel development at the hemangioblast level, and contributes to both primitive and definitive hematopoiesis. Depletion of Runx1 also caused aberrant axonogenesis and abnormal distribution of Rohon-Beard cells, providing the first functional evidence of a role for vertebrate Runx1 in neuropoiesis. To provide a base for examining the role of Runx1 in leukemogenesis, we investigated the effects of transient expression of a human RUNX1-CBF2T1 transgene [product of the t(8;21) translocation in acute myeloid leukemia] in zebrafish embryos. Expression of RUNX1-CBF2T1 caused disruption of normal hematopoiesis, aberrant circulation, internal hemorrhages and cellular dysplasia. These defects reproduce those observed in Runx1-depleted zebrafish embryos and RUNX1-CBF2T1 knock-in mice. The phenotype obtained with transient expression of RUNX1-CBF2T1 validates the zebrafish as a model system to study t(8;21)-mediated leukemogenesis.
Use of Ultrasound to Enhance the Local Anesthetic Effect of Topically Applied Aqueous Lidocaine (1993)

It was concluded that ultrasound exposure to the legs of hairless mice along with topical 2% lidocaine solution rapidly induced an anesthetic effect.
Comparative genomic hybridization imaging by the one‐chip true‐color CCD camera Kappa CF 15 MC (1996)

In comparative genomic hybridization (CGH), quantitative measurement of fluorescence intensity ratios on metaphase chromosomes is the basic method for detecting copy number changes in the test DNA. The microscope images are usually acquired by high-resolution, highly sensitive, black and white (B&W) CCD cameras. This requires subsequent recording of the different color images using appropriate filter combinations for excitation and emission. We describe an alternative approach using the one-chip true-color CCD camera Kappa CF 15 MC and an Omega triple-bandpass filter for simultaneous registration of the three dyes Texas red, FITC, and DAPI. A detailed examination of the imaging properties of the system was performed. The camera response in the three color planes R, G, and B was evaluated, and calibration factors for image correction were calculated. An error estimate is given. A complete computer program for the image analysis of CGH experiments has been developed for an 80486 PC, using the commercially available software package Optimas as the basis for image recording. Examples that confirm the suitability of the system for ratio imaging in CGH are presented. The results were compared with others obtained from the same microscope slides using an established setup consisting of a B&W CCD camera (Photometrics) and a software program based on the TCL software package and run on a Macintosh Quadra 950. The results obtained using the two different systems were found to correspond closely. © 1996 Wiley-Liss, Inc.