gebhart/patrepeval huggingface dataset:
The 1998 NASPE Prospective Catheter Ablation Registry (2000)

The results of the NASPE Prospective Voluntary Registry are reported. A total of 3,357 patients were entered. For those undergoing atrioventricular (AV) junctional ablation (646 patients), the success rate was 97.4% and significant complications occurred in 5 patients. A total of 1,197 patients underwent AV nodal modification for AV nodal reentrant tachycardia, which was successful in 96.1% and the only significant complication was development of AV block (1%). Accessory pathway ablation was performed in 654 patients and was successful in 94%. Major complications included cardiac tamponade (7 patients), acute myocardial infarction (1 patient), femoral artery pseudoaneurysm (1 patient), AV block (1 patient), pneumothorax (1 patient), and pericarditis (2 patients). A total of 447 patients underwent atrial flutter ablation and acute success was achieved in 86% of patients. Significant complications included inadvertent AV block (3 patients), significant tricuspid regurgitation (1 patient), cardiac tamponade (1 patient), and pneumothorax (1 patient). Atrial tachycardia was attempted for 216 patients and the success rate was higher for those with right atrial (80%) or left atrial (72%) compared to those with septal foci (52%). A total of 201 patients underwent ablation for ventricular tachycardia. The success rate was higher for those with idiopathic ventricular tachycardia compared to those with ventricular tachycardia due to ischemic heart disease or cardiomyopathy. While the number of AV junction ablation were higher for those > 60 years of age, there was no significant difference in the success rate or incidence of complication comparing patients > or = 60 to those < 60 years of age. In addition, we found no differences in incidence of success or complications comparing large volume centers (> 100 ablation/year) with lower volume centers or between teaching and non-teaching hospitals.
Specific immune response to a synthetic peptide derived from outer surface protein C of Borrelia burgdorferi predicts protective borreliacidal antibodies (2000)

In a previous study, we described the development of a new specific serodiagnostic test for Lyme disease involving enzyme-linked immunosorbent assay and a synthetic peptide, OspC-I. The OspC-I peptide is derived from part of the outer surface protein C (OspC) amino acid sequence of Borrelia burgdorferi and is located in the region conserved among B. burgdorferi sensu stricto or sensu lato isolates. In this study, we demonstrate that sera containing antibodies against OspC-I from patients with early Lyme disease had borreliacidal activity against isolates of three genospecies of Lyme disease spirochete, B. burgdorferi B31, B. garinii HP1 and B. afzelii HT61. However, the borreliacidal activity against B. burgdorferi, which has not been isolated in Japan, was weaker than that against the other species. Vaccination of mice with OspC-I induced the production of anti-OspC-I antibodies in serum with borreliacidal activity. The immune mouse serum had significantly higher levels of borreliacidal activity against HP1 and HT61, than against B31. Neutralization of borreliacidal activity with anti-IgM antibodies showed that the borreliacidal activity of anti-OspC-I antibodies in serum was due to IgM. Furthermore, mice vaccinated with OspC-I were protected against challenge with HP1 and HT61, but not fully protected against infection with B31. These results suggest that OspC-I is not only a specific antigen for use in serodiagnostic tests for Lyme disease, but is also a potential candidate for a Lyme disease vaccine in Japan.
Interleukin-2 killer cells: in vitro evaluation of combination with prothymosin alpha. (1994)

Interleukin-2 (IL-2) is a potent inducer of lymphokine-activated killer (LAK) activity against both NK-sensitive and NK-resistant tumor cell lines. IL-2 therapy has been associated with clinical responses, but these responses have occurred only with high, toxic doses of the cytokine. Since prothymosin alpha (ProT alpha) is able to enhance the spontaneous NK activity of cells from normal donors, we studied the effect of ProT alpha on LAK activity by IL-2. The lysis of K562 and Daudi cells by effector cells cultured with IL-2 was increased time dependently when cultures also contained ProT alpha. PBLC was separated by discontinuous density centrifugation in the LGL-enriched fractions. Within the CD16+ population, all effector cell precursors were CD2+, but the effector population after IL-2 or IL-2 + ProT alpha activation also contained CD16+CD2- cells; the CD2 molecule is thus indispensable for induction of LAK activity by IL-2 or IL-2 + ProT alpha but not for the action of activated LAK cells (or for the enhancing effect of ProT alpha). Within the CD3- CD16+ LGL population, 5 micrograms/ml ProT alpha plus 50 U/ml IL-2 was able to induce p70 IL-2R expression to a similar extent to 100 U/ml of IL-2. The use of ProT alpha to enhance the induction of LAK activity by IL-2 may be able to improve immunotherapy of cancer.
Detection of telomerase inhibitors based on g-quadruplex ligands by a modified telomeric repeat amplification protocol assay. (2002)

The telomeric repeat amplification protocol (TRAP) is commonly used to evaluate telomerase activity in tissues or cell extracts and also to determine the inhibitory properties of small molecules against telomerase. The recent discovery of G-quadruplex ligands as potent telomerase inhibitors prompted us to examine the accuracy of TRAP to be used to screen such class of molecules. Because of the specific feature of the TS primer, TRAP only allows the detection of G-quadruplex-induced telomerase inhibition after the synthesis of four TTAGGG repeats by telomerase and may thus lead to misinterpretations during screening assays. We have developed a TRAP-G4 assay that will allow the unambiguous detection of the inhibitory properties of a G-quadruplex ligand on telomerase activity and is able to discriminate them from other telomerase inhibitors.
PCR : essential data (1995)

Background to PCR and Its Application Areas (C. Newton). Setting Up a PCR Laboratory (C. Newton). Instruments (C. Newton). Nucleic Acid Substrates (C. Newton). Thermostable DNA Polymerases (C. Newton). Primers (C. Newton). The Synthesis of Chemically Labeled PCR Primers (T. Brown & D. Brown). Protocol Optimization and Reaction Specificity (S. Powell). Contamination Avoidance (C. Newton). Use of 5' Chemically Labeled Primers in PCR (J. Grzybowski, et al.). Detection of PCR Products (L. MacCallum). Purification of PCR Products (C. Newton). Cloning PCR Products (C. Newton). Miscellaneous Data (C. Newton). Troubleshooting (C. Newton). Manufacturers and Suppliers (C. Newton). References. Further Reading. Appendix. Index.
Stereotactic radiosurgical treatment of sphenopalatine neuralgia (1997)

Sphenopalatine neuralgia is a rare craniofacial pain syndrome that is characterized by unilateral pain in the orbit, mouth, nose, and posterior mastoid process. During attacks of pain, vasomotor activity often results in ipsilateral nasal drainage, eye irritation, and lacrimation. The authors present a patient with a 15-year history of sphenopalatine neuralgia who underwent stereotactic radiosurgery targeted at the sphenopalatine ganglion, with initial pain relief, and repeated radiosurgery 17 months later for partial pain recurrence. Two years following radiosurgery, the patient is pain free, no longer suffering from nasal discharge and eye irritation.
Protection of hamsters against Clostridium difficile ileocaecitis by prior colonisation with non-pathogenic strains (1985)

Prior colonisation of clindamycin-treated hamsters with non-toxigenic strains of C. difficile protected them from subsequent colonisation with a toxigenic pathogenic strain. In total, 13 of 18 'protected' hamsters survived for up to 27 days whereas all 27 animals challenged with the toxigenic strain alone died within 48 h. Protection was not evident if a heat-killed suspension was used or if the colonising non-toxigenic strain was first removed with vancomycin. No antitoxic activity could be detected in the faeces of animals colonised with the non-toxigenic strains. Other species of clostridia did not protect against the lethal effects of subsequent exposure to the toxigenic strain. Conversely, non-toxigenic strains would not protect the animals from the lethal effects of a different clostridial pathogen, C. spiroforme. In most cases, even in the protected animals, the toxigenic strain eventually became dominant and caused disease, with translocation across the gut wall occurring early in the disease process. It was also shown that a non-toxigenic strain of C. difficile can adhere to gut mucosa. It is proposed that the protection afforded by the non-toxigenic strains may be due to competition for ecological niches.
Inhibition of the alpha-ν integrins with a cyclic RGD peptide impairs angiogenesis, growth and metastasis of solid tumours in vivo (2002)

Anti-angiogenetic cancer therapy is a potential new form for treatment of solid tumours. The alpha(v)-integrins (alpha(v)beta3, alpha(v)beta5) mediate the contact of activated endothelial cells to proteins of the extracellular matrix during tumour angiogenesis as a prerequisite for survival of endothelial cells. The aim of this study was to investigate the effects of application of a methylated cyclic RGD-peptide as an alpha(v)-integrin antagonist on angiogenesis, microcirculation, growth and metastasis formation of a solid tumour in vivo. Experiments were performed in the dorsal skinfold preparation of Syrian Golden hamsters bearing the amelanotic hamster melanoma A-Mel-3. Animals were injected intraperitoneally with a methylated cyclic RGD-peptide every 12 h, the control group received an inactive peptide. Microcirculatory parameters of tumour angiogenesis including functional vessel density, red blood cell velocity, vessel diameter and leucocyte-endothelium interaction were analysed using intravital microscopy. In an additional study the effects on growth and metastasis of subcutaneous A-Mel-3 were quantified. Functional vessel density was markedly reduced on day 3 in treated animals compared to controls (37.2 +/- 12.1 vs 105.2 +/- 11.2 cm(-1); mean +/- s.e.m.; P<0.05) and increased subsequently in both groups. Red blood cell velocity at day 3 was below values of controls (0.026 +/- 0.01 vs 0.12 +/- 0.03 mm x s(-1); P<0.05). No differences were observed in vessel diameters and leucocyte-endothelium interaction was almost absent in both groups. Furthermore, growth and metastasis of subcutaneous tumours after administration of the cyclic RGD-peptide was significantly delayed in comparison to controls (P<0.05). Inhibition of alpha(v)-integrins by a cyclic RGD-peptide resulted in significant reduction of functional vessel density, retardation of tumour growth and metastasis in vivo. Taken together, these results implicate RGD-peptides as agents which have anti-tumour and anti-metastatic activity in vivo.
An intragenic suppressor in the cytochrome c oxidase I gene of mouse mitochondrial DNA (2003)

We report here the identification of a cell line containing single and double missense mutations in cytochrome c oxidase (COX) subunit I gene of mouse mitochondrial DNA. When present in homoplasmy, the single mutant displays a normal complex IV assembly but a significantly reduced COX activity, while the double mutant almost completely compensates the functional defect of the first mutation. We discuss the potential structural consequences of those mutations based on the modeled structure of mouse complex IV. Based on genetic, biochemical and molecular analyses of cultured mouse cells we infer that: (i) deleterious mutations can arise and become predominant; (ii) cultured cells can maintain several mtDNA haplotypes at stable frequencies; (iii) the respiratory chain has little spare COX capacity; and (iv) the size of a cavity in the vicinity of Val421 in CO I of animal COX may affect the function of the enzyme.
Phage φ29 Terminal Protein Residues Asn80 and Tyr82 Are Recognition Elements of the Replication Origins (1999)

Initiation of phage phi29 DNA replication starts with the recognition of the origin of replication, located at both ends of the linear DNA, by a heterodimer formed by the phi29 terminal protein (TP) and the phi29 DNA polymerase. The parental TP, covalently linked to the DNA ends, is one of the main components of the replication origin. Here we provide evidence that recognition of the origin is mediated through interactions between the TP of the TP/DNA polymerase heterodimer, called primer TP, and the parental TP. Based on amino acid sequence comparisons, various phi29 TP mutants were generated at conserved amino acid residues from positions 61 to 87. In vitro phi29 DNA amplification analysis revealed that residues Asn80 and Tyr82 are essential for functional interaction between primer and parental TP required for recognition of the origin of replication. Although these mutant TPs can form functional heterodimers with phi29 DNA polymerase that are able to recognize the origin of replication, these heterodimers are not able to recognize an origin containing a mutant TP.
Engineering Microneedle Patches for Vaccination and Drug Delivery to Skin (2017)

Microneedle patches (MNPs) contain arrays of solid needles measuring hundreds of microns in length that deliver drugs and vaccines into skin in a painless, easy-to-use manner. Optimal MNP design balances multiple interdependent parameters that determine mechanical strength, skin-insertion reliability, drug delivery efficiency, painlessness, manufacturability, and other features of MNPs that affect their performance. MNPs can be made by adapting various microfabrication technologies for delivery of small-molecule drugs, biologics, and vaccines targeted to the skin, which can have pharmacokinetic and immunologic advantages. A small number of human clinical trials, as well as a large and growing market for MNP products for cosmetics, indicate that MNPs can be used safely, efficaciously, and with strong patient acceptance. More advanced clinical trials and commercial-scale manufacturing will facilitate development of MNPs to realize their potential to dramatically increase patient access to otherwise-injectable drugs and to improve drug performance via skin delivery.
A New Laparoscopic Morcellator Using an Actuated Wire Mesh and Bag (2013)

Laparoscopic morcellation is a technique used in gynecological surgeries such as hysterectomy and myomectomy to remove uteri and uterine fibroids (leiomyomas) through a small abdominal incision. Current morcellators use blades or bipolar energy to cut tissue into small pieces that are then removed through laparoscopic ports in a piecewise manner. These existing approaches have several limitations; (1) they are time consuming as the tissue must be manually moved over the devices during the cutting step and removal is piecewise, (2) they can lead to accidental damage to surrounding healthy tissue inside the body and (3) they do not provide safe containment of tissue during the morcellation process which can lead to seeding (spreading and regrowth) of benign or potentially cancerous tissue. This paper describes a laparoscopic morcellator that overcomes these limitations through a new design that is based on an enclosed, motor-actuated mesh that applies only an inward-directed cutting force to the tissue after it has been loaded into the protective mesh and bag. The deterministic design approach that led to this concept is presented along with the detailed electromechanical design. The prototype is tested on soft vegetables and an animal model to demonstrate successful morcellation and how the device would be compatible with current clinical practice. Results show that the time required to morcellate with the new device for a set of tests on animal tissue is relatively uniform across samples with widely varying parameters. Including tissue manipulation and extraction time, the new device is shown to have an improvement in terms of speed over current morcellators. The mean time for cutting animal tissue ranging from 100 g to 360 g was 30 s with small variations due to initial conditions. The time for cutting is expected to remain approximately constant as tissue size increases. There is also minimal risk of the protective bag ripping due to the inward-cutting action of the mesh, thereby potentially significantly reducing the risk of seeding during clinical procedures; thus, further increasing patient safety. Finally, this design may be applicable to other procedures involving removal of tissue in nongynecologic surgeries, such as full or partial kidney or spleen removal.
Prenatal screening for chromosome abnormalities (1998)

An abnormal chromosome complement (aneuploidy) contributes significantly to fetal loss during pregnancy, as well as to perinatal morbidity and mortality. The contribution of chromosomal abnormalities to fetal loss decreases as pregnancy continues with an estimated 50% of first trimester spontaneous abortions due to chromosomal abnormalities, but only 5% of stillbirths (after 28 weeks). Prenatal screening for aneuploidy (in particular Down syndrome) can be undertaken using maternal serum biochemistry, fetal ultrasound or a combination of both. In this chapter the advantages and disadvantages of screening programmes currently in use, or undergoing evaluation, will be reviewed.
Alterations in the morphology of dendrites and dendritic spines in the nucleus accumbens and prefrontal cortex following repeated treatment with amphetamine or cocaine (1999)

Repeated treatment with psychostimulant drugs produces changes in brain and behaviour that far outlast their initial neuropharmacological actions. The nature of persistent drug-induced neurobehavioural adaptations is of interest because they are thought to contribute to the development of dependence and addiction, and other forms of psychopathology, e.g. amphetamine psychosis. There are many reports that psychostimulants produce biochemical adaptations in brain monoamine systems, especially dopamine systems. The purpose of the present study was to determine if they might also alter the morphology of neurons in brain regions that receive monoaminergic innervation. Rats were given repeated injections of either amphetamine or cocaine, or, to control for general motor activity, allowed access to a running wheel. They were then left undisturbed for 24-25 days before their brains were processed for Golgi-Cox staining. Treatment with either amphetamine or cocaine (but not wheel running experience) increased the number of dendritic branches and the density of dendritic spines on medium spiny neurons in the shell of the nucleus accumbens, and on apical dendrites of layer V pyramidal cells in the prefrontal cortex. Cocaine also increased dendritic branching and spine density on the basilar dendrites of pyramidal cells. In addition, both drugs doubled the incidence of branched spines on medium spiny neurons. It is suggested that some of the persistent neurobehavioural consequences of repeated exposure to psychostimulant drugs may be due to their ability to reorganize patterns of synaptic connectivity in the nucleus accumbens and prefrontal cortex.
Comparison of Hydrogen Sulfide Transport Properties in Fluorinated and Nonfluorinated Polymers (2006)

Permeability coefficients of hydrogen sulfide in fluorinated polymers are anomalously low when compared to its permeability in nonfluorinated polymers. As a result, fluoropolymer membranes have unusual selectivities for gas pairs involving H2S. For example, while the mixture CO2/H2S selectivity is 0.66 for nonfluorinated, rubbery poly(dimethylsiloxane), this selectivity is 8.0 for a fluoroelastomer composed of tetrafluoroethylene, perfluoromethyl vinyl ether, and perfluoro-8-cyano-5-methyl-3,6-dioxa-1-octene (TFE/PMVE/8CNVE) and 27 for a glassy, cyclic perfluoroether (Cytop) under similar test conditions. The low H2S permeability in fluoropolymers is caused primarily by unexpectedly low H2S solubility in the fluorinated polymer matrices. For instance, H2S solubility in a Teflon AF copolymer of tetrafluoroethylene and 2,2-bis(trifluoromethyl)-4,5-difluoro-1,3-dioxole is approximately 5 times lower than the value predicted by a correlation of solubility with gas critical temperature. This low solubility is not related to penetrant size or condensability effects but rather is caused by unfavorable molecular interactions between H2S and fluoropolymers. As a result of this unusual solubility behavior, fluorinated glassy polymers are more resistant to H2S-induced plasticization than nonfluorinated glasses. These findings may prove useful in emerging membrane applications that involve H2S, such as natural gas treatment.
The Problem of Passenger Genes in Transgenic Mice (2007)

Gene targeted or transgenic mice are frequently created on one genetic background and the mutation then transferred to a second genetic background by a series of backcrosses, with selection for the mutation at each generation. This is the same experimental design as that used in the production of classical congenic strains in which a genomic region from a “donor” strain is transferred to the background of a “recipient” strain by backcrossing and selection for ten or more generations. While the strategy largely results in the replacement of the donor background with the recipient background, the region flanking the selected gene remains of donor origin. Thus, the genes in this flanking region are “passengers” that travel with the selected gene, and when comparing transgenic (or knockout) mice with non-transgenic littermates, allelic differences in the passenger genes can conceivably influence the traits of interest. It now appears that this passenger gene effect may be an important confounder in studies of cardiovascular and metabolic traits that are influenced by dozens of common variations present among inbred mouse strains. Here, we discuss the problem and some approaches to avoid it.
The insulinotropic actions of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (7–37) in normal and diabetic subjects (1994)

Despite similar glycemic profiles, higher insulin levels are achieved following oral versus intravenous administration of glucose. This discrepancy is due to the incretin effect and is believed to be mediated via stimulation of beta-cells by hormone(s) released from the gut. The leading gut hormone candidates are glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide (GLP-1). To determine the relative insulinotropic activity of these peptides, we infused GLP-1(7-37) and GIP into normal subjects and patients with non-insulin dependent diabetes mellitus (NIDDM). In normal subjects during euglycemia, GLP-1(7-37) stimulated insulin release, whereas GIP did not. Using the Andres clamp technique, we established stable hyperglycemia for 2 h (5.4 mmol/l above the basal level). During the second hour, either GIP, GLP-1(7-37), or both were infused in normal healthy volunteers and in patients with NIDDM. In normal subjects, at a glucose level of 10.4 mmol/l, the 90-120 min insulin response was 279 pmol/l. GIP at a dose of 1, 2 or 4 pmol/kg/min augmented the 90-120 min insulin response by 69, 841 and 920 pmol/l, while GLP-1(7-37), at a dose of 1.5 pmol/kg/min augmented the insulin response by 2106 pmol/l. When both hormones were administered simultaneously, the augmentation was additive--2813 pmol/l. In the diabetic subjects, GIP had no effect, while GLP-1(7-37) augmented the insulin response by 929 pmol/l. We conclude that in normal healthy subjects, GLP-1(7-37), on a molar basis, is several times more potent than GIP at equivalent glycemic conditions. The additive insulinotropic effect suggests that more than one incretin may be responsible for the greater insulin levels observed following oral administration of glucose compared to the intravenous route. In NIDDM, GIP had no insulinotropic effect, while GLP-1(7-37) had a marked effect. This suggests that GLP-1(7-37) may have therapeutic potential as a hypoglycemic agent in NIDDM patients.