gebhart/patrepeval huggingface dataset:
Use of a Fluorescence Spectroscopic Readout To Characterize the Interactions of Cdc42Hs with Its Target/Effector, mPAK-3 (1997)

The family of p21-activated kinases (PAKs) has been shown to contain a domain that can independently bind to the Ras-like proteins Cdc42Hs and Rac. We have expressed a 72 amino acid recombinant form of this p21-binding domain (PBD) from mPAK-3 in Escherichia Coli for use in structure-function studies. The protein can be purified on a nickel affinity resin due to a hexa-His tag that is incorporated onto the amino terminus of the domain. PBD binds to Cdc42Hs in a guanine nucleotide-dependent manner as demonstrated by a novel fluorescence assay that takes advantage of the spectroscopic properties of N-methylanthraniloyl (Mant)-guanine nucleotides. Ionic strength has little effect on the affinity of PBD for Cdc42Hs, but alkaline pH values tend to weaken the interaction. We have shown that the inhibition of the GTPase activity of Cdc42Hs, as well as a previously undescribed inhibition of guanine nucleotide dissociation, is mediated by the PBD portion of the mPAK-3 molecule. These findings suggest that PBD binding alters the geometry of the guanine nucleotide binding site on Cdc42Hs, perhaps as an outcome of the target/effector molecule binding in close proximity to the nucleotide domain. We therefore tested if mutations in the effector region of Cdc42Hs (32-40), which in Ras are very close to the guanine nucleotide binding site, had any effect on PBD binding. Changing tyrosine 32 to lysine (Y32K) resulted in a small (5-fold) inhibition of PBD binding, but the very conservative mutation D38E yielded at least a 50-fold decrease in affinity. Finally, the catalytic domain of the GTPase activating protein, Cdc42-GAP, was shown to inhibit PBD binding in a competitive manner, indicating that this target molecule and the negative regulator (GAP) bind to overlapping sites on the Cdc42Hs molecule.
Simultaneous Recovery of DNA and RNA from Formalin-Fixed Paraffin-Embedded Tissue and Application in Epidemiologic Studies (2010)

Analysis of DNA, RNA, and protein extracted from tissue specimens in epidemiologic studies is useful for assessing etiologic heterogeneity, mechanisms of carcinogenesis, and biomarkers for prognosis and prediction of treatment responses. Fresh-frozen tissue samples may provide optimal quality nucleic acids, but pose multiple logistical considerations, including rapid access to tissues before histopathologic examination and specialized equipment for freezing, transport, and storage; in addition, morphology is often compromised. In contrast, formalin-fixed paraffin-embedded (FFPE) tissue samples, including enormous archives of existing specimens, represent a valuable source of retrospective biological material for epidemiologic research, although presenting different limitations compared with frozen samples. Recent efforts have made progress toward enhancing the utility of FFPE specimens for molecular analyses, including DNA studies, and increasingly for RNA and other macromolecules. Here, we report the method that we used to simultaneously recover DNA and RNA from FFPE tissue specimens with appreciable quantity and quality and discuss briefly the application of tumor markers in epidemiologic studies.
Rapid Plasticity of Human Cortical Movement Representation Induced by Practice (1998)

The process of acquiring motor skills through the sustained performance of complex movements is associated with neural plasticity. However, it is unknown whether even simple movements, repeated over a short period of time, are effective in inducing cortical representational changes. Whether the motor cortex can retain specific kinematic aspects of a recently practiced movement is also unknown. We used focal transcranial magnetic stimulation (TMS) of the motor cortex to evoke isolated and directionally consistent thumb movements. Thumb movements then were practiced in a different direction. Subsequently, TMS came to evoke movements in or near the recently practiced direction for several minutes before returning to the original direction. To initiate a change of the TMS-evoked movement direction, 15 or 30 min of continuous training were required in most of the subjects and, on two occasions, as little as 5 or 10 min. Substantially smaller effects followed more direct stimulation of corticofugal axons with transcranial electrical stimulation, pointing to cortex as the site of plasticity. These findings suggest that the training rapidly, and transiently, established a change in the cortical network representing the thumb, which encoded kinematic details of the practiced movement. This phenomenon may be regarded as a short-term memory for movement and be the first step of skill acquisition.
Site-specific glycosylation of recombinant rat and human soluble CD4 variants expressed in Chinese hamster ovary cells. (1993)

The rat and human forms of the T-cell surface glycoprotein CD4 share a common glycosylation site at the Asn270/271 position but differ with respect to the locations of the second glycosylation sites at Asn159 (rat) and Asn300 (human). The glycosylation of soluble recombinant forms of human and rat CD4 (sCD4) expressed in Chinese hamster ovary cells has been characterized. The most obvious differences between the rat and human sCD4 oligosaccharides were the greater abundance of oligomannose and hybrid oligosaccharides on rat sCD4 and the presence of oligosaccharides carrying a terminal alpha-galactose residue on human sCD4. This is the first report of the occurrence of alpha-galactose residues on a glycoprotein expressed in Chinese hamster ovary cells. Comparison of mutant rat sCD4 molecules with single glycosylation sites and glycopeptides indicated that site-specific and independent processing occurred at each glycosylation site. The glycosylation at the conserved site at Asn270 of rat sCD4 was identical to that seen for the equivalent site in human sCD4, and the oligomannose and hybrid structures were restricted to the nonconserved site at Asn159 in rat sCD4. However, there was more oligosaccharide processing at this site in a truncated form of rat sCD4 consisting of the two NH2-terminal domains. These results indicate that not only the local three-dimensional structure but also domain interactions can influence the processing at individual glycosylation sites.
Reflection on the installation of cell signal transduction theory (2001)

Cell signal transduction theory exceedingly changes cell biology concepts and finds more and more new mechanisms and new methods of the study in cell biology. In the process of its formation and progress, it transplants and grafts new principle and new methods of informatics. Furthermore it promotes human beings to make more clear with the complicated life system. The transplantation research on life phenomena and rules has lain a good foundation and accelerated the coming of biologic electronics and biologic informatics era.
Surfactant protein D in human lung diseases (2006)

The lung is continuously exposed to inhaled pollutants, microbes and allergens. Therefore, the pulmonary immune system has to defend against harmful pathogens, while an inappropriate inflammatory response to harmless particles must be avoided. In the bronchoalveolar space this critical balance is maintained by innate immune proteins, termed surfactant proteins. Among these, surfactant protein D (SP-D) plays a central role in the pulmonary host defence and the modulation of allergic responses. Several human lung diseases are characterized by decreased levels of bronchoalveolar SP-D. Thus, recombinant SP-D has been proposed as a therapeutical option for cystic fibrosis, neonatal lung disease and smoking-induced emphysema. Furthermore, SP-D serum levels can be used as disease activity markers for interstitial lung diseases. This review illustrates the emerging role of SP-D translated from in vitro studies to human lung diseases.
Innate Immune Response to Adenovirus (2005)

Adenovirus is a common infectious pathogen in both children and adults. It is a significant cause of morbidity in immunocompetent people living in crowded living conditions and of mortality in immunocompromised hosts. It has more recently become a popular vehicle for gene therapy applications. The host response to wild-type infection and gene therapy vector exposure involves both the innate and adaptive immune systems. The initial innate immune response is associated with the severe acute manifestations of adenovirus infection and also plays a significant role in acute toxicity owing to adenovirus vector exposure. This review discusses the innate immune response primarily during wild-type adenovirus infection because this serves as the basis for understanding the response during both natural infection and exposure to adenovirus vectors.
Low-dose interleukin-11 has activity in patients with bone marrow failure (2004)

2538 Background: Interleukin-11 (IL-11) stimulates the proliferation of hematopoietic stem cells and megakaryocyte progenitors and induces megakaryocyte maturation. The objectives of this study were to assess the toxicity, safety and efficacy of low-dose recombinant IL-11 in patients with bone marrow failure (BMF). Methods: Eligibility criteria included chronic BMF-related thrombocytopenia due to myelodysplastic syndromes (MDS), graft failure, chemotherapy, or aplastic anemia (AA); no chemotherapy for >2 months; no progressive disease; performance status 0–2 (Zubrod scale); and no ATG treatment for >3 months (AA patients). IL-11 was administered daily at a dose of 10 μg/kg s.c. for 2 weeks followed by a 2-week rest period. Two induction courses were given, followed by maintenance daily or every other day therapy for as long as hematologic improvement without Grade 3–4 toxicities was seen. Results: Thirty-three patients were evaluable (MDS, n=14; AA, n=16; prolonged thrombocytopenia following stem cell transplantation or chemotherapy, n=3). The median age was 58 years (range, 5–85). The median platelet count was 17 x 109/L (range, 1–48 x 109/L). Three patients (9%) had poor risk cytogenetics. Nine patients (27%) responded to IL-11 (MDS=6, AA=3). Of these, 3 patients treated with IL-11 alone (n=1) or IL-11 plus other growth factors (n=2) showed multilineage recovery. The median time to response was 0.9 months (range, 0.3–11.0 months) and the median response duration was 3.0 months (range, 1.4–34.5+ months). Among responders, the median increment in platelet count was 111 x 109/L (range, 43–165 x 109/L) net increase above the baseline platelet counts. Factors associated with higher response rates in univariate analysis were age >50 years (p=0.008), diagnosis of MDS vs. AA (p=0.025), and creatinine level >1mg/dl (p=0.0004). The most common side effects were Grade 1–2 lower extremity edema, conjunctival injections and fatigue. Grade 3 toxicities, which may have been related to IL-11 included arrhythmia (n=1) and transient ischemic attack (n=1). Ten patients (30%) had no side effects. Conclusions: Low-dose IL-11 has activity in patients with BMF and is generally well tolerated. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Wyeth Inc.
Idiopathic Pulmonary Fibrosis (2001)

Idiopathic pulmonary fibrosis is a rapidly progressive illness of unknown cause characterized by sequential acute lung injury with subsequent scarring and end-stage lung disease. Treatment at present remains largely supportive, with evidence that patients' satisfaction and survival may be improved by referral to centers specializing in the evaluation of interstitial lung diseases. Although no drug therapy has clearly been demonstrated to benefit patients with idiopathic pulmonary fibrosis, a number of novel investigational agents hold promise for future study. Given the poor prognosis associated with idiopathic pulmonary fibrosis, patients should be referred to regional centers of expertise for enrollment in therapeutic clinical trials or for lung transplantation.
Decontamination with vaporized hydrogen peroxide is effective against Mycobacterium tuberculosis (2005)

Fumigation with VHP represents an alternative to formaldehyde fumigation, particularly for decontamination of animal rooms in tuberculosis research laboratories.
Positive and Negative Regulation of Angiogenesis by Soluble Vascular Endothelial Growth Factor Receptor-1 (2018)

Vascular endothelial growth factor receptor (VEGFR)-1 exists in different forms, derived from alternative splicing of the same gene. In addition to the transmembrane form, endothelial cells produce a soluble VEGFR-1 (sVEGFR-1) isoform, whereas non-endothelial cells produce both sVEGFR-1 and a different soluble molecule, known as soluble fms-like tyrosine kinase (sFlt)1-14. By binding members of the vascular endothelial growth factor (VEGF) family, the soluble forms reduce the amounts of VEGFs available for the interaction with their transmembrane receptors, thereby negatively regulating VEGFR-mediated signaling. In agreement with this activity, high levels of circulating sVEGFR-1 or sFlt1-14 are associated with different pathological conditions involving vascular dysfunction. Moreover, sVEGFR-1 and sFlt1-14 have an additional role in angiogenesis: they are deposited in the endothelial cell and pericyte extracellular matrix, and interact with cell membrane components. Interaction of sVEGFR-1 with &alpha;5&beta;1 integrin on endothelial cell membranes regulates vessel growth, triggering a dynamic, pro-angiogenic phenotype. Interaction of sVEGFR-1/sFlt1-14 with cell membrane glycosphingolipids in lipid rafts controls kidney cell morphology and glomerular barrier functions. These cell⁻matrix contacts represent attractive novel targets for pharmacological intervention in addition to those addressing interactions between VEGFs and their receptors.
Receptor-associated Protein Interacts with Amyloid-β Peptide and Promotes Its Cellular Uptake (2009)

Brain amyloid-beta (Abeta) peptide accumulation and aggregation are critical events in the pathogenesis of Alzheimer disease. Increasing evidence has demonstrated that LRP1 is involved in Alzheimer disease pathogenesis. The physiological ligands of LRP1, including apoE, play significant roles in the cellular clearance of Abeta. The receptor-associated protein (RAP) is a specialized chaperone for members of the low density lipoprotein receptor family. RAP shares structural and receptor-binding properties with apoE. Here, we show that RAP binds to both Abeta40 and Abeta42 in a concentration-dependent manner and forms complexes with them. Fluorescence-activated cell sorter analysis showed that RAP significantly enhances the cellular internalization of Abeta in different cell types, including brain vascular smooth muscle, neuroblastoma, glioblastoma, and Chinese hamster ovary cells. This effect of RAP was confirmed by fluorescence microscopy and enzyme-linked immunosorbent assay. RAP binds to both LRP1 and heparin; however, the ability of RAP to enhance Abeta cellular uptake was blocked by heparin and heparinase treatment but not by LRP1 deficiency. Furthermore, the effects of RAP were significantly decreased in heparan sulfate proteoglycan-deficient Chinese hamster ovary cells. Our findings reveal that RAP is a novel Abeta-binding protein that promotes cellular internalization of Abeta.
Ill-convergence of Godard blind equalizers in data communication systems (1991)

The existence of stable undesirable equilibria for the Godard algorithm is demonstrated through a simple autoregressive (AR) channel model. These undesirable equilibria correspond to local but nonglobal minima of the underlying mean cost function, and thus permit the ill-convergence of the Godard algorithms which are stochastic gradient descent in nature. Simulation results confirm predicted misbehavior. For channel input of constant modulus, it is shown that attaining the global minimum of the mean cost necessarily implies correct equalization. A criterion is also presented for allowing a decision at the equalizer as to whether a global or nonglobal minimum has been reached.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Cloned DNA probes regionally mapped to human Chromosome 21 and their use in determining the origin of nondisjunction (1985)

A number of unique sequence recombinant DNA clones were isolated from a recombinant DNA library constructed from DNA enriched for chromosome 21 by flow sorting. Of these, five were mapped to chromosome 21 using a somatic cell hybrid. Regional mapping of these probes and of a probe previously assigned to chromosome 21, was carried out with the aid of chromosome 21 rearrangements using both chromosome sorting and a somatic cell hybrid. Three probes were shown to be located on either side of the breakpoint 21q21.2. Two of the probes were shown to identify restriction fragment length polymorphisms (RFLPs) with high rare-allele frequencies (0.46 and 0.43). A Bgl II RFLP revealed the parental origin of non-disjunction in three of ten families with Down's syndrome.
Radiowave excitation of resonant D.C. electromotive force in metals (2005)

Summary form only given, as follows. It is predicted that the conditions of the parametric cyclotron resonance may be realized at the excitation of long cyclotron waves in metals with external electromagnetic waves. It leads to the appearance of the resonant d.c. electromotive force in metals.
Octapeptides deduced from the neuropeptide receptor-like pattern of antigen T4 in brain potently inhibit human immunodeficiency virus receptor binding and T-cell infectivity. (1986)

The differentiation antigen T4, present on the helper/inducer subset of T lymphocytes, is thought to serve as the receptor for the human immunodeficiency virus (HIV). We find that a 60-kDa protein, immunoprecipitable by monoclonal antibody (mAb) OKT4, is present on membranes from human brain as well as human T cells. Furthermore, the radioiodinated HIV envelope glycoprotein [125I-labeled gp120 (125I-gp120)] can be specifically covalently affixed to a molecule present on rat, monkey, and human brain membranes to yield a complex that is indistinguishable from that formed on human T cells. T4 antigen has been studied on unfixed squirrel monkey, rat, and human brain sections by autoradiography using the mAb OKT4. A highly conserved neuroanatomical pattern has been demonstrated, suggesting an analogous organization in these three mammalian brains. Furthermore, the localization of 125I-gp120 receptor binding appears similar to that of T4 and is highly reminiscent of patterns for many previously characterized neuropeptide receptors. A computer-assisted analysis of gp120 suggested that a previously unremarkable octapeptide sequence within the gp120 protein, which we have synthesized and termed "peptide T," may play an important role in HIV attachment. Thus, peptide T and three rationally designed peptide analogs, each with a systematic amino acid substitution, potently inhibit specific 125I-gp120 binding to brain membranes. Additionally, when tested in a viral infectivity assay, these peptides show the same rank order and similar absolute potency to block HIV infection of human T cells. Thus, peptide T may provide a useful pharmacological or immunological basis for the control and treatment of AIDS.
Age‐ and individual‐related specificities in the effects of standardized ginseng extract on learning and memory (experiments on rats) (1987)

Abstract Using a two‐way active avoidance with punishment (electric shock) reinforcement (shuttle box) we investigated the effects of Panax ginseng extract, standardized according to the content of ginsenosides on learning and memory in 2‐, 10‐, and 22‐month old Wistar rats and in rats of the same age (5‐month old) which, after a preliminary training with the same method, had been classified as ‘good’, ‘poor’ and ‘satisfactory’ learners. In experiments on rats of different ages G115 was administered orally daily for 10 consecutive days before training at increasing doses of 3, 10, 30 and 100 mg/kg body weight. The animals were trained for 5 days and the retention test was given 14 days after the last administration of G115 (10 days after the last training session). In experiments on rats with different learning capabilities G115 was administered orally at a dose of 10 mg/kg for 10 days after shuttle box training. The retention test was performed on the day following the last treatment with G115. It was found that G115 exerted the most favourable effects on learning and memory when these processes were decayed as a result either of senescence or of individual specificities.
Safety and Feasibility of Topical Application of Limonene as a Massage Oil to the Breast (2012)

Our studies showed that limonene is bio available in mammary tissue after topical orange oil application in mice and this novel route of administration to the breast is safe and feasible in healthy women.
Extensive plaque psoriasis successfully treated with adalimumab (HumiraR) (2005)

Journal Article Extensive plaque psoriasis successfully treated with adalimumab (Humira®) Get access M.J. Sladden, M.J. Sladden Department of Dermatology, Leicester Royal Infirmary, Leicester LE1 5WW, U.K. E‐mail: m.sladden@doctors.org.uk Search for other works by this author on: Oxford Academic Google Scholar N.J. Mortimer, N.J. Mortimer Department of Dermatology, Leicester Royal Infirmary, Leicester LE1 5WW, U.K. E‐mail: m.sladden@doctors.org.uk Search for other works by this author on: Oxford Academic Google Scholar P.E. Hutchinson P.E. Hutchinson Department of Dermatology, Leicester Royal Infirmary, Leicester LE1 5WW, U.K. E‐mail: m.sladden@doctors.org.uk Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 152, Issue 5, 1 May 2005, Pages 1091–1092, https://doi.org/10.1111/j.1365-2133.2005.06582.x Published: 01 May 2005
The Nature and Mechanisms of Dental Fluorosis in Man (1990)

Any use of fluorides, whether systemic or topical, in caries prevention and treatment in children results in ingestion and absorption of fluoride into the blood circulation. The mineralization of teeth under formation may be affected so that dental fluorosis may occur. Dental fluorosis reflects an increasing porosity of the surface and subsurface enamel, causing the enamel to appear opaque. The clinical features represent a continuum of changes ranging from fine white opaque lines running across the tooth on all parts of the enamel to entirely chalky white teeth. In the latter cases, the enamel may be so porous (or hypomineralized) that the outer enamel breaks apart posteruptively and the exposed porous subsurface enamel becomes discolored. These changes can be classified clinically by the TF index to reflect, in an ordinal scale, the histopathological changes associated with dental fluorosis. Compared with Dean's and the TSIF index, we consider the TF index to be more precise. Recent studies on human enamel representing the entire spectrum of dental fluorosis have demonstrated a clear association between increasing TF score and increasing fluoride content of the enamel. So far, no useful data on dose (expressed in mg fluoride/kg b.w.)-response (dental fluorosis) relationships are available. In this paper, we have, therefore, re-evaluated the original data by Dean et al. (1941, 1942), Richards et al. (1967), and Butler et al. (1985) from the USA, by applying the equation of Galagan and Vermillion (1957) which permits the calculation of water intake as a function of temperature.(ABSTRACT TRUNCATED AT 250 WORDS)