gebhart/patrepeval huggingface dataset:
The molecular and cellular biology of heart failure (1995)

We review recent publications that use molecular and cellular biology to explore the diagnosis and treatment of cardiovascular diseases that have relevance to heart failure. Familial hypertrophic cardiomyopathy has now been shown to be due to mutations not only in the previously described beta myosin heavy chain gene, but also in the troponin T and alpha-tropomyosin genes, thus providing some symmetry to the idea that this is a molecular disease of the sarcomere. The basis for a type of familial dilated cardiomyopathy without substantial skeletal muscle involvement, caused by a mutation in the dystrophin gene, has been explored. However, by-and-large, the disease basis for most patients with dilated cardiomyopathy remains a molecular mystery. The role of a polymorphism in the angiotensin-converting enzyme gene was examined as a risk factor for a number of cardiovascular diseases. In animal models, the hypothesis that the devolution from hypertrophy to heart failure includes alterations in the molecular direction of extracellular matrix production gained some support. The experimental foundation was laid this year for the concept of and approach to cardiomyocytoplasty--the molecular and cellular treatment of heart failure by augmentation, repair, or replacement of cardiac myocytes--by experiments in cardiac gene transfer and transgenic animals. Gene causes and cures for restenosis after angioplasty garnered considerable attention. As we gain greater understanding of the molecular basis for disease, we will also have to increase our wisdom in the application of genetic testing.
A comparison of esterified estrogens with and without methyltestosterone: effects on endometrial histology and serum lipoproteins in postmenopausal women. (1993)

These findings underscore the importance of addressing area-level social inequalities, if uptake of mammography screening guidelines is to be realized across all social strata.
High resolution digital holographic microscopy with a wide field of view based on a synthetic aperture technique and use of linear CCD scanning (2008)

Theoretical analysis shows that, to improve the resolution and the range of the field of view of the reconstructed image in digital lensless Fourier transform holography, an effective solution is to increase the area and the pixel number of the recorded digital hologram. A new approach based on the synthetic aperture technique and use of linear CCD scanning is presented to obtain digital holographic images with high resolution and a wide field of view. By using a synthetic aperture technique and linear CCD scanning, we obtained digital lensless Fourier transform holograms with a large area of 3.5 cm x 3.5 cm (5000 x 5000 pixels). The numerical reconstruction of a 4 mm object at a distance of 14 cm by use of a Rayleigh-Sommerfeld integral shows that a theoretically minimum resolvable distance of 2.57 microm can be achieved at a wavelength of 632.8 nm. The experimental results are consistent with the theoretical analysis.
Role of cholesteryl ester transfer protein in selective uptake of high density lipoprotein cholesteryl esters by adipocytes (2004)

Previous reports attributed cholesteryl ester transfer protein (CETP)-mediated HDL cholesteryl ester (CE) selective uptake to the CETP-mediated transfer of CE from HDL to newly secreted apolipoprotein B-containing lipoproteins, which are then internalized by the LDL receptor (LDL-R). CETP has also been implicated in the remodeling of HDL, which renders it a better substrate for selective uptake by scavenger receptor class B type I (SR-BI). However, CETP-mediated selective uptake of HDL3-derived CE was not diminished in LDL-R null adipocytes, SR-BI null adipocytes, or in the presence of the receptor-associated protein. We found that monensin treatment or energy depletion of the SW872 liposarcoma cells with 2-deoxyglucose and NaN3 had no effect on CETP-mediated selective uptake, demonstrating that endocytosis is not required. This is supported by data indicating that CETP transfers CE into a compartment from which it can be extracted by unlabeled HDL. CETP could also mediate the selective uptake of HDL3-derived triacylglycerol (TG) and phospholipid (PL). The CETP-specific kinetics for TG and CE uptake were similar, and both reached saturation at approximately 5 microg/ml HDL. In contrast, CETP-specific PL uptake did not attain saturation at 5 microg/ml HDL and was approximately 6-fold greater than the uptake of CE. We propose two possible mechanisms to account for the role of CETP in selective uptake.
Pathogenic Mechanism of the FIG4 Mutation Responsible for Charcot-Marie-Tooth Disease CMT4J (2011)

CMT4J is a severe form of Charcot-Marie-Tooth neuropathy caused by mutation of the phosphoinositide phosphatase FIG4/SAC3. Affected individuals are compound heterozygotes carrying the missense allele FIG4-I41T in combination with a null allele. Analysis using the yeast two-hybrid system demonstrated that the I41T mutation impairs interaction of FIG4 with the scaffold protein VAC14. The critical role of this interaction was confirmed by the demonstration of loss of FIG4 protein in VAC14 null mice. We developed a mouse model of CMT4J by expressing a Fig4-I41T cDNA transgene on the Fig4 null background. Expression of the mutant transcript at a level 5 × higher than endogenous Fig4 completely rescued lethality, whereas 2 × expression gave only partial rescue, providing a model of the human disease. The level of FIG4-I41T protein in transgenic tissues is only 2% of that predicted by the transcript level, as a consequence of the protein instability caused by impaired interaction of the mutant protein with VAC14. Analysis of patient fibroblasts demonstrated a comparably low level of mutant I41T protein. The abundance of FIG4-I41T protein in cultured cells is increased by treatment with the proteasome inhibitor MG-132. The data demonstrate that FIG4-I41T is a hypomorphic allele encoding a protein that is unstable in vivo. Expression of FIG4-I41T protein at 10% of normal level is sufficient for long-term survival, suggesting that patients with CMT4J could be treated by increased production or stabilization of the mutant protein. The transgenic model will be useful for testing in vivo interventions to increase the abundance of the mutant protein.
Is the light chain subcellular localization an important factor in botulinum toxin duration of action? (2004)

Botulinum neurotoxins (BoNT) are therapeutic proteins that are specific, potent, and effective. They are highly specific in binding to motor neurons but do not bind to other non-neuronal cells. These proteins are zinc-dependent endopeptidases that inhibit exocytosis by specific cleavage of the SNARE (soluble N-ethylmaleimide-sensitive factor-attachment protein-receptor) proteins involved in vesicle docking and fusion. The therapeutic effect of BoNT/A in humans lasts from 3 to 12 months, depending upon the condition treated. Data from animal and cell culture models suggests that the long-lasting duration of inhibition of neurotransmitter release induced by BoNT/A maybe due to the persistence of the endopeptidase activity of the light chain (LC/A) in cells, interactions of the cleaved substrates, and/or the response of the nerve to the temporary disruption of communication with its target tissue. We have analyzed the subcellular localization of the light chains from serotypes A, B, and E and have demonstrated that each light chain displays a distinct distribution within cells. LC/A localizes at the plasma membrane, LC/B is dispersed throughout the cell including the nucleus, and LC/E is mainly cytosolic. Localization is similar in non-neuronal cell lines, suggesting that the signals involved in proper subcellular localization are within the LC sequences and the moiety the light chain interacts with is present in both neuronal and non-neuronal cells.
Systemic and Upper and Lower Airway Inflammation at Exacerbation of Chronic Obstructive Pulmonary Disease (2005)

Exacerbation of COPD is associated with pan-airway inflammation; the systemic inflammatory response is proportional to that occurring in the lower airway and greater in the presence of a bacterial pathogen.
The Front Line of Enteric Host Defense against Unwelcome Intrusion of Harmful Microorganisms: Mucins, Antimicrobial Peptides, and Microbiota (2006)

The intestinal tract is a complex ecosystem that combines resident microbiota and the cells of various phenotypes with complex metabolic activities that line the epithelial wall. The intestinal cells that make up the epithelium provide physical and chemical barriers that protect the host against the unwanted intrusion of microorganisms that hijack the cellular molecules and signaling pathways of the host and become pathogenic. Some of the organisms making up the intestinal microbiota also have microbicidal effects that contribute to the barrier against enteric pathogens. This review describes the two cell lineages present in the intestinal epithelium: the goblet cells and the Paneth cells, both of which play a pivotal role in the first line of enteric defense by producing mucus and antimicrobial peptides, respectively. We also analyze recent insights into the intestinal microbiota and the mechanisms by which some resident species act as a barrier to enteric pathogens. Moreover, this review examines whether the cells producing mucins or antimicrobial peptides and the resident microbiota act in partnership and whether they function individually and/or synergistically to provide the host with an effective front line of defense against harmful enteric pathogens.
Long-term culture of human antigen-specific cytotoxic T-cell lines. (1978)

Long-term cultures of human cytotoxic T-cell lines (H-CTLL) were established. H-CTLL cells were strictly dependent on growth upon a T-cell growth factor (TCGF) produced by phytohemagglutinin-stimulated normal human peripheral blood lymphocytes. H-CTLL cells were maintained in TCGF-dependent exponential proliferative culture for over 4 mo during which time they continued to mediate stimulator antigen-specific cytotoxicity as measured by a 4-h 51Cr-release assay. H-CTLL cells recovered from cryopreserved stocks and re-established in long-term culture demonstrated similar high levels of antigen-specific cytotoxicity. H-CTLL cells were 95--100% E-rosette positive and expressed normal T and Ia-like cell surface markers. The ability to sustain differentiated antigen-specific T-effector cells in long-term culture may provide a new means for the study of both the mechanism and regulation of T-cell-mediated immunity.
Surface modification and evaluation of some commonly used catheter materials. I. Surface properties (1983)

Double catheter systems consisting of a stiff outer catheter and a flexible, buoyant, flow-directed, inner catheter which is often balloon-tipped have been employed with increasing frequency recently in both therapeutic and diagnostic procedures. Their use, however, has been restricted because of the excessive friction generated between the two catheters. In an attempt to decrease friction between polymers commonly used as catheter materials, oxidation of polyethylene, fluorinated ethylene-propylene copolymer, poly(vinyl chloride), silicone rubber, and polystyrene surfaces was induced by exposing the polymers to radio frequency glow discharge (RFGD) in a helium environment. All polymers were surface characterized utilizing x-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), and contact angle measurements before and after oxidation. This article describes the materials and methods used to fabricate and characterize the polymer surfaces and the results of the characterization. The results indicate that increases in oxygen concentration at the surface of the polymers and decreases in air-water contact angles occur with increased RFGD exposure time. Plateau values were usually obtained after 5-30 s exposure time, yet no apparent changes in surface topography were noted by scanning electron microscopy. The hydrophilic surfaces produced were stable for up to three months storage time in air.
Cortisol concentration in gilts provided with rubber mats during winter season (2013)

Stress is a biological response to an event that the individual perceives as a threat to its homeostasis. Restrictive accommodation with concrete slatted flooring in modern pig production might act as a stressor for animals. Due to welfare concern, emphasis is put on their environment enrichment. The aim of this study was to assess the level of stress in pigs kept on rubber-coated floor. The study was conducted in the pig farm service unit in winter. Two groups of control and experimental (n=9 each) gilts were investigated during the 28-day production cycle. Both groups were accommodated in gestation stalls with concrete slatted floor ; in the experimental group, the floor was additionally coated with adjusted rubber mats. Stress level was assessed by determination of cortisol concentration (µg/dL) in gilt blood serum. Blood was sampled on cycle days 1, 8, 15 and 28 from cranial vena cava. Cortisol concentration was measured by the competitive chemiluminescent immunoenzymatic assay. Serum cortisol concentration was lower in experimental group than in control group on all measurement days. The difference recorded on day 28 and difference in the mean cortisol concentration throughout the study period were statistically significant (P<0.05 both). The results obtained may be related to the thermal insulating effect of mats and improved comfort for gilts in cold season. In conclusion, the use of rubber mats proved to be an efficient management tool in reducing stress in gilts.
Management of hyperphosphataemia of chronic kidney disease: lessons from the past and future directions (2002)

A historical look at research in hyperphosphataemia of chronic kidney disease over the last 40 years shows remarkable advances in our understanding of this abnormality and in the technology used to manage it. Phosphate binders, which have become a mainstay in the management of hyperphosphataemia, have evolved from the early use of aluminium gels to calcium salts, to novel, non-absorbed, aluminium-free, calcium-free agents such as sevelamer hydrochloride, and to magnesium-, iron-, and lanthanum-based compounds. With recent advances, clinical management of this complication of chronic renal disease is evolving from adequate care to optimal care, such that new standards in phosphorous management are being set, and various parameters of patient care are being integrated to optimize outcomes and minimize side effects. This paper provides a historical view of the clinical management of hyperphosphataemia, and looks to advances in treatment that are changing the course of renal bone disease management.
An RNA thermometer (1999)

The expression of a conserved set of heat shock proteins is induced when cells grown at low temperatures are shifted to higher temperatures. Heat shock proteins are molecular chaperones or proteases that act to fold, translocate, or degrade proteins that appear to be misfolded or denatured upon heat shock. The heat shock response has been the focus of much research, and how the temperature signal is sensed and transduced to the biosynthetic machinery has been studied extensively. The s (RpoH) alternative s-factor, which is encoded by the rpoH gene, is a key regulator of the Escherichia coli heat shock response (for review, see Gross 1996; Missiakas et al. 1996). Upon a temperature shift from 30°C to 42°C, s accumulates and directs RNA polymerase to the promoters of the heat shock genes (Fig. 1). Earlier studies showed that both increased synthesis and stability lead to the increased levels of s. The activity of s and its association with RNA polymerase are also modulated by heat shock. A great deal has been learned about the increased stability of s in response to increased temperature. During normal growth the half-life of s is ∼1 min; upon upshift the half-life is increased to ∼5 min. Interestingly, the heat shock proteins DnaK, DnaJ, GrpE and HflB, whose expression is regulated by s, function to destabilize s. These proteins interact with s, sequestering it away from RNA polymerase and targeting it for degradation. Misfolded proteins that accumulate after heat shock appear to titrate the DnaK, DnaJ, and GrpE chaperones and the HflB protease away from s. Therefore, the pool of misfolded proteins is thought to be one measure of elevated temperature in the cell. Increased s synthesis was known to occur at the level of translation. However, although the E. coli heat shock response has been under investigation for many years, the thermometer signaling the need for increased translation was not known. In this issue Morita et al. (1999) show that the secondary structure of the rpoH mRNA itself is a thermosensor. These investigators present strong correlations between the expression of rpoH–lacZ fusions and the predicted and actual thermostability of the rpoH mRNA secondary structure. In addition, rpoH–lacZ expression levels correlate with the formation of rpoH mRNA–30S ribosome– tRNAf Met complexes. Thus, the melting of the rpoH mRNA secondary structure at high temperature leads to ribosome binding and increased s synthesis. Here, I summarize the findings that led to this conclusion. I also contrast the rpoH mRNA with other proposed RNA and protein thermometers.
The development of autoimmunity in C57BL/6 lpr mice correlates with the disappearance of natural killer type 1-positive cells: evidence for their suppressive action on bone marrow stem cell proliferation, B cell immunoglobulin secretion, and autoimmune symptoms. (1993)

F1 hybrid mice are able to acutely reject parental marrow grafts, a phenomenon that is due to natural killer type 1-positive (NK1+) cells. Circumstantial evidence had suggested that the antigenic determinants recognized by these cells are self-antigens, leading to the hypothesis that the physiological role of NK1+ cells is a downregulatory or suppressive function on bone marrow stem cell proliferation and lymphocyte function. In analyzing this hypothesis it is shown here that in young mice there is a temporal correlation between appearance of NK1+ cells in the spleen and the ability to reject allogeneic marrow or to suppress endogenous stem cell proliferation. The reverse situation exists in mice expressing the homozygous lpr gene. Whereas in young mice cells with NK1+ phenotype are demonstrable, these cells disappear with age, i.e., at the time autoimmunity develops. Concomitant with the disappearance of NK1+ cells, the ability to reject marrow grafts and to control endogenous stem cell proliferation also vanishes. The suggestion that the development of autoimmunity is causally related to the disappearance of NK1+ cells is supported by experiments in which NK1+ cells were either eliminated by antibody injection or increased by adoptively transferring cell populations enriched for NK1+ cells into lpr mice. It is shown that removal of cells enhances autoimmunity, whereas injection of NK1+ cells delays the onset of autoimmunity. In vitro assays are presented that demonstrate that suppression of autoantibody-secreting B cells is due to two NK1+ cell populations, one that expresses CD3 and causes specific suppression and one that lacks CD3 and causes nonspecific suppression.
Many Parallel Losses of infA from Chloroplast DNA during Angiosperm Evolution with Multiple Independent Transfers to the Nucleus (2001)

We used DNA sequencing and gel blot surveys to assess the integrity of the chloroplast gene infA, which codes for translation initiation factor 1, in >300 diverse angiosperms. Whereas most angiosperms appear to contain an intact chloroplast infA gene, the gene has repeatedly become defunct in approximately 24 separate lineages of angiosperms, including almost all rosid species. In four species in which chloroplast infA is defunct, transferred and expressed copies of the gene were found in the nucleus, complete with putative chloroplast transit peptide sequences. The transit peptide sequences of the nuclear infA genes from soybean and Arabidopsis were shown to be functional by their ability to target green fluorescent protein to chloroplasts in vivo. Phylogenetic analysis of infA sequences and assessment of transit peptide homology indicate that the four nuclear infA genes are probably derived from four independent gene transfers from chloroplast to nuclear DNA during angiosperm evolution. Considering this and the many separate losses of infA from chloroplast DNA, the gene has probably been transferred many more times, making infA by far the most mobile chloroplast gene known in plants.
[Experimental assessment of some pharmacodynamic features of ketoprofen lysine. Pain relief activity, antipyretic effects, anti-inflammatory activity, anti-platelet aggregation activity and interference with the biosynthesis of prostaglandins]. (1981)

An experimental assessment was made of the analgesic, anti-inflammatory and platelet anticlumping activity of ketoprophene lysine, and its effect on body temperature and prostaglandin synthesis. The drug's pharmacodynamics was very similar to that of ketoprophene and its gastric tolerance was better. It was also well tolerated by the dog joint surfaces and cardiovascular apparatus when given i.m. or i.v., even at doses higher than those advised for man, or when infiltrated in ketoreceptor areas.
High quality multiband LPC coding of speech at 2.4 kbit/s (1991)

Until recently good quality digital speech transmission was not possible below about 9.6 kbit/s. With the development of code excited linear prediction (CELP) and multiband excitation (MBE) vocoders,2 high quality digital speech transmission became possible at bit rates as low as 4.8 kbit/s. Below 4.8 kbit/s however, vocoders such as LPC-103 and the channel vocoder4 which can only produce synthetic and unnatural speech are still in use. A new coding scheme termed the multiband LPC (MB-LPC) vocoder is proposed, which produces good and natural quality speech at 2.4 kbit/s. Subjective performance of speech at 2.4kbit/s produced by the CELP is very close to MBE coded speech at 4.8 kbit/s. Informal listening tests have shown that in most cases people could not tell the difference between the new 2.4kbit/s MB-LPC coder and the 4.8 kbit/s MBE vocoder.
WFS a simple shared file system for a distributed environment (1979)

WFS is a shared file server available to a large network community. WFS responds to a carefully limited repertoire of commands that client programs transmit over the network. The system does not utilize connections, but instead behaves like a remote disk and reacts to page-level requests. The design emphasizes reliance upon client programs to implement the traditional facilities (stream IO, a directory system, etc.) of a file system. The use of atomic commands and connectionless protocols nearly eliminates the need for WFS to maintain transitory state information from request to request. Various uses of the system are discussed and extensions are proposed to provide security and protection without violating the design principles.