gebhart/patrepeval huggingface dataset:
Effect of heparin on the in vivo release and clearance of human platelet factor 4 (1983)

Intravenous injection of heparin (100 U/kg) into normal volunteers resulted in an increase of platelet factor 4 (PF4) level in platelet- poor plasma from a mean value of 18.1 +/- 6.6 ng/ml before the injection to 257.9 +/- 68.3 ng/ml at 5 min after injection. PF4 antigen isolated from “postheparin plasma” by adsorption on heparin-agarose and elution with 2.0 M NaCl and “authentic PF4” isolated from human platelets showed identical patterns of migration as determined by sodium dodecylsulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Material released by washed human platelets was injected intravenously into rats. The clearance of PF4 followed a biphasic exponential pattern. The half-lives (T1/2) for the fast and slow components for control rats were 1.2 and 17.1 min. Heparin significantly extended the half-life of human PF4 in rat circulation. The clearance of PF4 injected together with heparin followed a single component model with a half-life of 27.6 min. Administration of heparin to rats that had been previously injected with human platelet releasate resulted in a 30-fold increase of plasma PF4 level in their circulation. The clearance of PF4 from the circulation of these rats (T1/2 = 45 min) fitted a single component model. We propose that PF4 is originally secreted by platelets into circulation and subsequently bound reversibly to vascular sites from which it can be released back into the circulation by heparin. The fast component of PF4 clearance that is abolished by heparin may reflect binding of this protein to the endothelial cells.
Benefit of Atrial Pacing in Sleep Apnea Syndrome (2002)

In patients with sleep apnea syndrome, atrial overdrive pacing significantly reduces the number of episodes of central or obstructive sleep apnea without reducing the total sleep time.
Cellulosome assembly revealed by the crystal structure of the cohesin–dockerin complex (2003)

The utilization of organized supramolecular assemblies to exploit the synergistic interactions afforded by close proximity, both for enzymatic synthesis and for the degradation of recalcitrant substrates, is an emerging theme in cellular biology. Anaerobic bacteria harness a multiprotein complex, termed the "cellulosome," for efficient degradation of the plant cell wall. This megadalton catalytic machine organizes an enzymatic consortium on a multifaceted molecular scaffold whose "cohesin" domains interact with corresponding "dockerin" domains of the enzymes. Here we report the structure of the cohesin-dockerin complex from Clostridium thermocellum at 2.2-A resolution. The data show that the beta-sheet cohesin domain interacts predominantly with one of the helices of the dockerin. Whereas the structure of the cohesin remains essentially unchanged, the loop-helix-helix-loop-helix motif of the dockerin undergoes conformational change and ordering compared with its solution structure, although the classical 12-residue EF-hand coordination to two calcium ions is maintained. Significantly, internal sequence duplication within the dockerin is manifested in near-perfect internal twofold symmetry, suggesting that both "halves" of the dockerin may interact with cohesins in a similar manner, thus providing a higher level of structure to the cellulosome and possibly explaining the presence of "polycellulosomes." The structure provides an explanation for the lack of cross-species recognition between cohesin-dockerin pairs and thus provides a blueprint for the rational design, construction, and exploitation of these catalytic assemblies.
Insulin Delivery Systems: Do They Need a Glucose Sensor? (1982)

New systems are being developed for continuous insulin infusion in diabetes mellitus. Of these, the bedside closed-loop system (artificial B-cell) normalizes measured blood glucose in the fasting and fed states, while favorably altering other fuel substrates and hormone levels in short-term studies of 1-2 days. More recent portable, external open-loop insulin delivery systems have been developed which can be programmed to achieve similar results in long-term studies in animals and humans. This is accomplished without the need for continuous glucose sensing. The partial metabolic normalization achieved is not compromised by physical exercise, and unacceptably low blood glucose levels are rarely observed. Further development and application of these new systems will enable researchers to establish whether the achievement of ideal metabolic control in diabetes can be realized with or without sensors for glucose or other metabolites.
A Comprehensive Panel of Near-Full-Length Clones and Reference Sequences for Non-Subtype B Isolates of Human Immunodeficiency Virus Type 1 (1998)

Non-subtype B viruses cause the vast majority of new human immunodeficiency virus type 1 (HIV-1) infections worldwide and are thus the major focus of international vaccine efforts. Although their geographic dissemination is carefully monitored, their immunogenic and biological properties remain largely unknown, in part because well-characterized virological reference reagents are lacking. In particular, full-length clones and sequences are rare, since subtype classification is frequently based on small PCR-derived viral fragments. There are only five proviral clones available for viruses other than subtype B, and these represent only 3 of the 10 proposed (group M) sequence subtypes. This lack of reference sequences also confounds the identification and analysis of mosaic (recombinant) genomes, which appear to be arising with increasing frequency in areas where multiple sequence subtypes cocirculate. To generate a more representative panel of non-subtype B reference reagents, we have cloned (by long PCR or lambda phage techniques) and sequenced 10 near-full-length HIV-1 genomes (lacking less than 80 bp of long terminal repeat sequences) from primary isolates collected at major epicenters of the global AIDS pandemic. Detailed phylogenetic analyses identified six that represented nonrecombinant members of HIV-1 subtypes A (92UG037.1), C (92BR025. 8), D (84ZR085.1 and 94UG114.1), F (93BR020.1), and H (90CF056.1), the last two comprising the first full-length examples of these subtypes. Four others were found to be complex mosaics of subtypes A and C (92RW009.6), A and G (92NG083.2 and 92NG003.1), and B and F (93BR029.4), again emphasizing the impact of intersubtype recombination on global HIV-1 diversification. Although a number of clones had frameshift mutations or translational stop codons in major open reading frames, all the genomes contained a complete set of genes and three had intact genomic organizations without inactivating mutations. Reconstruction of one of these (94UG114.1) yielded replication-competent virus that grew to high titers in normal donor peripheral blood mononuclear cell cultures. This panel of non-subtype B reference genomes should prove valuable for structure-function studies of genetically diverse viral gene products, the generation of subtype-specific immunological reagents, and the production of DNA- and protein-based subunit vaccines directed against a broader spectrum of viruses.
D/sup 2/PAMN: distributed dynamic power and error control algorithm for mobile networks (2002)

One critical issue in wireless systems is the efficient encoding of data in the presence of noise and Rayleigh fading. We analyze automatic repeat request (ARQ)-selective repeat and forward error correction control (FEC) algorithms using Markov chain model for mobile systems that can optimize the amount of battery energy consumed by transmitters. In this paper, we introduce an enhanced distributed algorithm which dynamically balances the combination of FEC and ARQ. The algorithm is shown to be suitable for both real time and non-real time multimedia environments. Extensive simulation indicates that our proposed algorithm outperforms existing schemes solely based on either FEC or ARQ and demonstrates the usefulness of our novel scheme.
Expression of the HER1–4 family of receptor tyrosine kinases in breast cancer (2003)

EGFr/HER1 and c-erbB-2/HER2 expression are associated with poor prognosis in breast cancer. The type I receptor tyrosine kinase (RTK) family to which they belong has four members (HER1-4). In this study, expression of HER1-4 and oestrogen receptor (ER) expression were determined by immunohistochemistry in 220 breast carcinomas. Elevated expression of HER1 was observed in 16.4%, HER2 in 22.8%, HER3 in 17.5%, and HER4 in 11.9% of these tumours. Patients whose tumours overexpressed HER1, 2 or 3 had reduced survival (p= <0.001), whereas those whose tumours overexpressed HER4 had increased survival (p=0.013); 38.6% of cases overexpressed one or more of HER1, 2 or 3. HER4 was rarely overexpressed with other HERs (1.4% of cases). Cox's multiple regression analysis demonstrated that overexpression of HER1/2/3, HER4, and standard prognostic indicators independently affected survival. HER1-3 expression was related to ER negativity (p<0.0001, chi2). Patients with ER-positive, HER1-3-positive tumours had a significantly poorer survival (p<0.001) than those with ER-positive/HER-negative or HER4-positive tumours. Expression of HER RTKs displays complex interactions between different family members. There is a strong interaction, in terms of survival, between HER expression and ER expression. The development of HER-targeted agents (eg Herceptin, Iressa), and agents targeted at the downstream signalling pathways, therefore provides new possibilities in the treatment of breast cancer.
A novel 7-modified camptothecin analog overcomes breast cancer resistance protein-associated resistance in a mitoxantrone-selected colon carcinoma cell line. (2001)

We selected a mitoxantrone-resistant HT29 colon carcinoma cell line (HT29/MIT) that exhibited a very high degree of resistance to the selecting agent and marked resistance to topotecan and SN38, but limited resistance to doxorubicin. The development of drug resistance was independent of expression of P-glycoprotein or multidrug resistance-associated protein but was associated with high up-regulation of the breast carcinoma resistance protein (BCRP) as shown by Western blot analysis. BCRP overexpression was associated with a reduced intracellular accumulation of topotecan, a known substrate for BCRP. Conversely, a lipophilic 7-modified camptothecin analogue (ST1481) displayed a complete lack of cross-resistance in HT29/MIT cells, suggesting that the drug was not a substrate for BCRP because no defects in intracellular accumulation were found. This conclusion is consistent with the antitumor efficacy of ST1481 against a BCRP-expressing tumor. These results may have therapeutic implications because the antitumor efficacy of ST1481 is in part related to a good bioavailability after oral administration, and the drug is currently under Phase I clinical evaluation.
Structural Classification of Toxic Amyloid Oligomers (2008)

Amyloid oligomers are believed to play important causal roles in many types of amyloid-related degenerative diseases. Many different laboratories have reported amyloid oligomers that differ in size, morphology, toxicity, and method of preparation or purification, raising the question of the structural relationships among these oligomer preparations. The structural plasticity that has been reported to occur in amyloids formed from the same protein sequence indicates that it is quite possible that different oligomer preparations may represent distinct structural variants. In view of the difficulty in determining the precise structure of amyloids, conformation- and epitope-specific antibodies may provide a facile means of classifying amyloid oligomer structures. Conformation-dependent antibodies that recognize generic epitopes that are specifically associated with distinct aggregation states of many different amyloid-forming sequences indicate that there are at least two fundamentally distinct types of amyloid oligomers: fibrillar and prefibrillar oligomers. Classification of amyloid oligomers according to their underlying structures may be a more useful and rational approach than relying on differences in size and morphology.
The purple pigments produced by acetylation of 2-(2-oxoindolin-3-yl)glyoxylates in the presence of pyridine. Some new evidence (1979)

As a result of the analysis of 13C n.m.r. spectra, a new structure (7) is preferred for the purple pigments obtained by the reactions of 2-(2-oxoindolin-3-yl)glyoxylates with acetic anhydride in the presence of pyridine. A mechanistic rationalisation of the formation of the pigments and their unusual rearrangement on oxidation with chromic acid are discussed.
Consumer’s Corner (1998)

No AccessPerspectives on Fluency and Fluency DisordersViewpoint1 Mar 1998Consumer’s Corner Bonnie Weiss Bonnie Weiss University of Buffalo Google Scholar More articles by this author https://doi.org/10.1044/ffd8.2.4 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationTrack Citations ShareFacebookTwitterLinked In "Consumer’s Corner." Perspectives on Fluency and Fluency Disorders, 8(2), p. 4 Additional Resources FiguresReferencesRelatedDetails Volume 8Issue 2March 1998Pages: 4-4 Get Permissions Add to your Mendeley library History Published in issue: Mar 1, 1998 Metrics Topicsasha-topicsleader-topicsasha-article-typesasha-sigsCopyright & Permissions© 1998 American Speech-Language-Hearing AssociationPDF DownloadLoading ...
The Effect of Sodium Salicylate and Aspirin on NF-κB (1995)

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Site-Specific Cleavage of a Yeast Chromosome by Oligonucleotide-Directed Triple-Helix Formation (1990)

Oligonucleotides equipped with EDTA-Fe can bind specifically to duplex DNA by triple-helix formation and produce double-strand cleavage at binding sites greater than 12 base pairs in size. To demonstrate that oligonucleotide-directed triple-helix formation is a viable chemical approach for the site-specific cleavage of large genomic DNA, an oligonucleotide with EDTA-Fe at the 5' and 3' ends was targeted to a 20-base pair sequence in the 340-kilobase pair chromosome III of Saccharomyces cerevisiae. Double-strand cleavage products of the correct size and location were observed, indicating that the oligonucleotide bound and cleaved the target site among almost 14 megabase pairs of DNA. Because oligonucleotide-directed triple-helix formation has the potential to be a general solution for DNA recognition, this result has implications for physical mapping of chromosomes.
Disruption of Growth Hormone Signaling Retards Early Stages of Prostate Carcinogenesis in the C3(1)/T Antigen Mouse (2005)

Recent epidemiological studies suggest that elevated serum titers of IGF-I, which are, to a large degree, regulated by GH, are associated with an increase in prostate cancer risk. The purpose of the current study was to develop the first animal models to directly test the hypothesis that a normal, functional GH/IGF-I axis is required for prostate cancer progression. The GH receptor (GHR) gene-disrupted mouse (Ghr(-/-)), which has less than 10% of the plasma IGF-I found in GHR wild-type mice, was crossed with the C3(1)/T antigen (Tag) mouse, which develops prostatic intraepithelial neoplasia driven by the large Tag that progress to invasive prostate carcinoma in a manner similar to the process observed in humans. Progeny of this cross were genotyped and Tag/Ghr(+/+) and Tag/Ghr(-/-) mice were killed at 9 months of age. Seven of eight Tag/Ghr(+/+) mice harbored prostatic intraepithelial neoplasia lesions of various grades. In contrast, only one of the eight Tag/Ghr(-/-) mice exhibited atypia (P < 0.01, Fischer's exact test). Disruption of the GHR gene altered neither prostate androgen receptor expression nor serum testosterone titers. Expression of the Tag oncogene was similar in the prostates of the two mouse strains. Immunohistochemistry revealed a significant decrease in prostate epithelial cell proliferation and an increase in basal apoptotic indices. These results indicate that disruption of GH signaling significantly inhibits prostate carcinogenesis.
The Quantification of Endolymphatic Hydrops in an Experimental Animal Model with Guinea Pigs (2004)

To better quantify endolymphatic hydrops in experimental guinea pigs, endolymphatic hydrops was induced by endolymphatic sac obliteration through an extradural posterior cranial fossa approach in the right ear. The area of the scala vestibuli and scala media of each turn on both cochlear midmodiolar sections was measured, using an automated computer-aided design (AutoCAD R14) software combined with a digital camera. No endolymphatic hydrops was observed in all nonoperated ears; however, various degrees of hydrops were present in all operated ears. The average maximum SMA (scala media area) ratio in the 4-week group (2.22 +/- 0.20) was greater than that in the control group (1.10 +/- 0.06). The average maximum SMA ratio of the 8-week group (4.04 +/- 0.52) was greater than that of the 4-week group (p < 0.05). This study provides a reliable methodologic base for the experimental study of Ménière's disease.
Site-specific interaction of DNA gyrase with DNA. (1981)

DNA gyrase, in the presence of the inhibitor oxolinic acid, can induce double-strand DNA breakage at specific sites. The sequences at several sites have been determined. In addition, the structure of complexes formed between DNA gyrase and restriction fragments containing an oxolinic acid-promoted cleavage site has been examined by DNase protection methods. DNA gyrase protects more than 120 base pairs of DNA against pancreatic DNase in a region surrounding the cleavage site. Protection is observed both in the presence and absence of oxolinic acid. Protected DNA flanking the cleavage site contains DNase I-sensitive sites spaced on the average 10 or 11 base pairs apart. This result supports the view that, in the DNA gyrase--DNA complex, the DNA is largely wrapped on the outside of the enzyme.
Discrimination of Mycobacterium tuberculosis complex bacteria using novel VNTR-PCR targets (2002)

The lack of a convenient high-resolution strain-typing method has hampered the application of molecular epidemiology to the surveillance of bacteria of the Mycobacterium tuberculosis complex, particularly the monitoring of strains of Mycobacterium bovis. With the recent availability of genome sequences for strains of the M. tuberculosis complex, novel PCR-based M. tuberculosis-typing methods have been developed, which target the variable-number tandem repeats (VNTRs) of minisatellite-like mycobacterial interspersed repetitive units (MIRUs), or exact tandem repeats (ETRs). This paper describes the identification of seven VNTR loci in M. tuberculosis H37Rv, the copy number of which varies in other strains of the M. tuberculosis complex. Six of these VNTRs were applied to a panel of 100 different M. bovis isolates, and their discrimination and correlation with spoligotyping and an established set of ETRs were assessed. The number of alleles varied from three to seven at the novel VNTR loci, which differed markedly in their discrimination index. There was positive correlation between spoligotyping, ETR- and VNTR-typing. VNTR-PCR discriminates well between M. bovis strains. Thirty-three allele profiles were identified by the novel VNTRs, 22 for the ETRs and 29 for spoligotyping. When VNTR- and ETR-typing results were combined, a total of 51 different profiles were identified. Digital nomenclature and databasing were intuitive. VNTRs were located both in intergenic regions and annotated ORFs, including PPE (novel glycine-asparigine-rich) proteins, a proposed source of antigenic variation, where VNTRs potentially code repeating amino acid motifs. VNTR-PCR is a valuable tool for strain typing and for the study of the global molecular epidemiology of the M. tuberculosis complex. The novel VNTR targets identified in this study should additionally increase the power of this approach.
Novel Benzamides as Selective and Potent Gastrokinetic Agents. III. Synthesis and Structure-Activity Relationships of 4-Amino-5-chloro-2-methoxy- and 2-Ethoxy-N-((4-substituted 2-morpholinyl)methyl)- benzamides. (1992)

A series of 4-amino-5-chloro-2-methoxy- and 2-ethoxy-N-[(4-substituted 2-morpholinyl)methyl]benzamides (11-64) were prepared and evaluated for gastrokinetic activity by determining their effects on the gastric emptying of phenol red semisolid meal in rats. The N-4 substituent includes alkyl, phenoxyalkyl, (4-fluorobenzoyl)alkyl, and heteroarylmethyl groups. The benzamide derivatives, having an isopropyl, isoamyl, neopentyl, 3-(4-chlorophenoxy)-propyl, or pyridylmethyl group at N-4, showed potent in vivo gastric emptying activity. In particular, 4-amino-5-chloro-2-ethoxy-N-[[4-(3-pyridylmethyl)-2- morpholinyl]methyl]benzamide (57b) was equipotent to the 4-fluorobenzyl analogue 1b (AS-4370 as its citrate) in the gastrokinetic activity on phenol red semisolid meal in rats and mice, and on resin pellet solid meal in rats. Moreover, compound 57b was free from dopamine D2 receptor antagonistic activity in both in vitro ([3H]spiperone binding) and in vivo (apomorphine-induced emesis in dogs) tests. Structure-activity relationships of compounds with various substituents at N-4 are also discussed.
Homotype resonant tunneling structures in molecular-beam epitaxially grown delta-doped GaAs (1992)

A homotype negative differential resistance (NDR) device in a GaAs delta-doped structure prepared by molecular-beam epitaxy is demonstrated. One Be and two Si delta-doped planes are inserted in the GaAs layer (i.e., n+-δn+-i-δp+-i-δn+-n+), to form the required resonant tunneling structure. Electrons transported from the conduction band of the n+ layer then, can resonantly tunnel through the light hole level of the δp+ induced quantum well. When the device is operated at room temperature, symmetrical NDR characteristics with high peak to valley current ratios of 3:1 are found to be comparable with those of the heterotype AlGaAs/GaAs double barrier structure. The experimentally determined peak voltage and current density are in good agreement with these theoretically calculated from a stationary-state transport model using two-band envelope function approximation. The effects of the delta-doped p plane and device parameters on NDR behavior are discussed.
Anti‐oxidants as modulators of immune function (2000)

In order to confirm the hypothesis of the immunomodulating action of anti-oxidants (bringing back altered immune function to more optimum values), the possibility that anti-oxidants may be useful in two experimental models of altered immune function has been studied. The first is a pathological model, that is, lethal murine endotoxic shock caused by an LPS injection of 100 mg/kg, in which the lymphocytes show increased adherence and depressed chemotaxis. The injection of N-acetylcysteine (150 mg/kg), which increased both functions in control animals, decreased adherence and increased chemotaxis in mice with endotoxic shock. The second is a physiological model; aged human subjects (70 +/- 5-year-old men) who, in their largest segment of population ('standard' group) showed an increased lymphocyte adherence and decreased lymphoproliferative response to mitogens compared with younger adults. The ingestion of vitamin E (200 mg daily for 3 months in this standard group) lowered adherence and stimulated lymphoproliferation. However, a smaller segment of the human population tested showed 'non-standard' values in these lymphocyte functions, that is, very low adherence and very high proliferation. In those subjects, vitamin E showed the opposite effects, namely adherence increase and depressed lymphoproliferation. In both age groups of men, these functions reached adult levels after vitamin E ingestion. These data suggest that anti-oxidants preserve adequate function of immune cells against homeostatic disturbances such as those caused by endotoxic shock and ageing.