gebhart/patrepeval huggingface dataset:
Pseudomonas aeruginosaBloodstream Infection: Importance of Appropriate Initial Antimicrobial Treatment (2005)

Pseudomonas aeruginosa bloodstream infection is a serious infection with significant patient mortality and health-care costs. Nevertheless, the relationship between initial appropriate antimicrobial treatment and clinical outcomes is not well established. This study was a retrospective cohort analysis employing automated patient medical records and the pharmacy database at Barnes-Jewish Hospital. Three hundred five patients with P. aeruginosa bloodstream infection were identified over a 6-year period (January 1997 through December 2002). Sixty-four (21.0%) patients died during hospitalization. Hospital mortality was statistically greater for patients receiving inappropriate initial antimicrobial treatment (n = 75) compared to appropriate initial treatment (n = 230) (30.7% versus 17.8%; P = 0.018). Multiple logistic regression analysis identified inappropriate initial antimicrobial treatment (adjusted odds ratio [AOR], 2.04; 95% confidence interval [CI], 1.42 to 2.92; P = 0.048), respiratory failure (AOR, 5.18; 95% CI, 3.30 to 8.13; P < 0.001), and circulatory shock (AOR, 4.00; 95% CI, 2.71 to 5.91; P < 0.001) as independent determinants of hospital mortality. Appropriate initial antimicrobial treatment was administered statistically more often among patients receiving empirical combination antimicrobial treatment for gram-negative bacteria compared to empirical monotherapy (79.4% versus 65.5%; P = 0.011). Inappropriate initial empirical antimicrobial treatment is associated with greater hospital mortality among patients with P. aeruginosa bloodstream infection. Inappropriate antimicrobial treatment of P. aeruginosa bloodstream infections may be minimized by increased use of combination antimicrobial treatment until susceptibility results become known.
Connecting actin monomers by iso-peptide bond is a toxicity mechanism of the Vibrio cholerae MARTX toxin (2008)

The Gram-negative bacterium Vibrio cholerae is the causative agent of a severe diarrheal disease that afflicts three to five million persons annually, causing up to 200,000 deaths. Nearly all V. cholerae strains produce a large multifunctional-autoprocessing RTX toxin (MARTX(Vc)), which contributes significantly to the pathogenesis of cholera in model systems. The actin cross-linking domain (ACD) of MARTX(Vc) directly catalyzes a covalent cross-linking of monomeric G-actin into oligomeric chains and causes cell rounding, but the nature of the cross-linked bond and the mechanism of the actin cytoskeleton disruption remained elusive. To elucidate the mechanism of ACD action and effect on actin, we identified the covalent cross-link bond between actin protomers using limited proteolysis, X-ray crystallography, and mass spectrometry. We report here that ACD catalyzes the formation of an intermolecular iso-peptide bond between residues E270 and K50 located in the hydrophobic and the DNaseI-binding loops of actin, respectively. Mutagenesis studies confirm that no other residues on actin can be cross-linked by ACD both in vitro and in vivo. This cross-linking locks actin protomers into an orientation different from that of F-actin, resulting in strong inhibition of actin polymerization. This report describes a microbial toxin mechanism acting via iso-peptide bond cross-linking between host proteins and is, to the best of our knowledge, the only known example of a peptide linkage between nonterminal glutamate and lysine side chains.
IL-10, a novel growth cofactor for mature and immature T cells. (1990)

We identified a new cytokine, B cell-derived T cell growth factor (B-TCGF), that is produced by a murine B cell lymphoma and induces proliferation of mature and immature thymocytes in the presence of IL-2 and IL-4. Both adult and day 15 fetal thymocytes (CD4-8-, CD4+8-, CD4-8+) proliferate strongly in the presence of IL-2, IL-4, and B-TCGF. B-TCGF alone does not stimulate thymocyte proliferation. B-TCGF appears to be identical to a novel cytokine whose cDNA was recently isolated at our institution, cytokine synthesis-inhibitory factor (CSIF; IL-10). rIL-10 has B-TCGF activity, and mAb specific for IL-10 inhibit the B-TCGF activity present in CH12 supernatants. Further studies have shown that day 15 fetal thymocytes cultured in the presence of IL-10, IL-2, and IL-4 remain CD4- and CD8- but exhibit increased CD3 expression. Adult CD4- CD8- thymocytes cultured under the same conditions proliferate whether they are CD3+ or CD3-. The CD3- population becomes enriched in CD3+ cells after 4 days of culture. IL-10 is secreted by day 15 fetal thymocytes, adult thymocytes, and adult splenocytes when stimulated via their TCR. IL-10 is strongly homologous to the EBV gene BCRFI, and BCRFI has CSIF activity. In contrast to IL-10, BCRFI does not exhibit detectable thymocyte-stimulating activity, suggesting the existence of at least two functional epitopes on the IL-10 molecule.
Effects on the Activity of the Enzyme Phosphoribosyl-Aminoimidazole Carboxylase, Involved in the Biosynthesis of Purine Nucleotides De Novo by Bi-Valent Metal Complexes of the Natural Substrate 5-Amino-1-β-D-Ribofuranosylimidazole-4-Carboxylic Acid 5′-Phosphate (1988)

Abstract A series of bi-valent metal complexes of 5-amino-l-β-D-ribofuranosylimida-zole-4-carboxylic acid and its 5′-phosphate derivative (CAIR), a central intermediate in de novo biosynthesis of purine nucleotides have been synthesised. The nucleotide complexes were found to affect the activity of the enzyme phosphoribosylaminoimidazole carboxylase (EC. 4.1.1.21).
Simultaneous measurement of temperature and strain using fibre Bragg gratings and Brillouin scattering (1997)

The authors report on the simultaneous measurement of temperature and strain in a single optical fibre. The measurements were made using a combination of a fibre Bragg grating element and a Brillouin scattering interrogation system, operating in different optical wavelength regimes, to determine the two parameters. The system has the potential to provide quasi-distributed determination of strain and temperature along a fibre.
Reversing anticoagulants both old and new. (2003)

Newer anticoagulant agents generally lack specific antidotes. Thus, careful choice of an anticoagulant agent and laboratory monitoring where appropriate are needed to minimize risk of bleeding complications.
Tree searched multi-stage vector quantization of LPC parameters for 4 kb/s speech coding (1992)

The authors present a tree searched multi-stage vector quantization (TS-MSVQ) scheme which achieves spectral distortion lower than 1 dB with low complexity and good robustness using 24 b/frame. The M-L search is used and it is shown that it achieves performance close to that of the optimal search for a relatively small M. The best performance/complexity trade-offs are obtained with relatively small size codebooks cascaded in a three-four stage configuration. Results for log-area ratio (LAR) and line spectral pain (LSP) parameters are presented. A training technique which reduces outliers at the expense of a slight average performance degradation is introduced. The robustness across different languages and input spectral shapings is studied. Finally, it is shown that TS-MSVQ significantly outperforms the split-codebook approach.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
The antipsoriatic drug dimethylfumarate strongly suppresses chemokine production in human keratinocytes and peripheral blood mononuclear cells (2001)

These results show the ability of DMF to inhibit the production of chemokines that may be critically involved in the development and perpetuation of psoriatic lesions. This might explain, at least in part, the beneficial effects of treatment with fumaric acid esters in psoriasis patients.
Clinical Observations with Topical Liposome-Encapsulated Interferon Alpha for the Treatment of Genital Papillomavirus Infections (1997)

This study reports the formulation and preliminary clinical testing of liposomes as a topical drug delivery system for interferon a (IFN α) in the treatment of genital human papillomavirus (HPV) infections. Intron A (IFN α-2b) was encapsulated into multilamellar liposomes, composed of soya phosphatidylcholine: cholesterol: stearic acid 2:1:1.4 molar ratio, by a modified solvent evaporation method (protein to phospholipid ratio 7±103IU/mg). The liposomes were in the size range of 0.5-2 μm as determined by electron microscopy. The incorporation of IFN α into liposomes was 91.7±2.2% (n=4). In an open trial, one female patient with exophytic warts and cervical HPV (type 6/11), responded to a treatment with 2.1 ±106 IU liposomal IFN α-2b per week for 12 weeks and 7±106 IU liposomal IFN α-2b per week for an additional 6 weeks externally administered in divided doses twice a day, and simultaneously 0.7±106 IU liposomal IFN α-2b per week intravaginally. Clinically the cervical lesion completely resolved at the end of the therapy, and the exophytic lesions decreased in size. In situ hybridization showed decreased focal staining for HPV DNA in biopsy tissue after treatment. The presence of IFN α was detected in the biopsy tissue by immunostaining. The male patient, treated with 2.1±106 IU liposomal IFN α-2b per week for 8 weeks showed decreased number of lesions at the end of the observation period.
BLINDNESS IN NEW SOUTH WALES An estimate of the prevalence and some of the contributing causes (1981)

The information available on the prevalence of blindness in Australia is examined in an attempt to estimate the number of blind people in New South Wales. Records of the causes of blindness made by the authors at the Royal Blind Society's Low Vision Clinic are then examined to estimate their relative significance. There are at least seven thousand people blind, out of a total population of 5,145,900. Macula pathology contributes 37.2% and 81.5% of those affected are over 60 years old. Diabetes is responsible for approximately 10%. Genetically determined disease causes 25% between ages 16 and 60 years. If blindness is to be prevented, a more detailed analysis of causes will be needed. This could be obtained by examination and coding of the records for Disability (Blind) Pensions at the Department of Social Security. Blindness in Aboriginals is not discussed.
Epidemiologic study of relationships between consumption of commercial canned food and risk of hyperthyroidism in cats (2004)

These findings suggest that the increasing prevalence of feline hyperthyroidism is not solely the result of aging of the cat population and that canned foods may play a role.
Stability of Olfactory Identification Deficits in Neuroleptic-Naive Patients With First-Episode Psychosis (2001)

Impairment in olfactory identification ability was apparent from the outset of psychotic illness and was not specific to schizophrenia or schizophreniform disorder. No change in the degree of this deficit was found after patients were stabilized and had responded to medication. The deficit could not be explained by peripheral factors that might contribute to olfactory identification ability, suggesting that it reflects central mechanisms.
Structural Analysis of N-Linked Sugar Chains of Human Blood Clotting Factor IX (2000)

The structures of N-glycans of human blood clotting factor IX were studied. N-Glycans liberated by hydrazinolysis were N-acetylated and the reducing-end sugar residues were tagged with 2-aminopyridine. The pyridylamino (PA-) sugar chains thus obtained were purified by HPLC. Each PA-sugar chain was analyzed by two-dimensional sugar mapping combined with glycosidase digestion. The major structures of the N-linked sugar chains of human factor IX were found to be sialotetraantennary and sialotriantennary chains with or without fucose residues. These highly sialylated sugar chains are located on the activation peptide of the protein.
Hyperphosphorylation of the Hepatitis C Virus NS5A Protein Requires an Active NS3 Protease, NS4A, NS4B, and NS5A Encoded on the Same Polyprotein (1999)

The nonstructural protein NS5A of hepatitis c virus (HCV) has been demonstrated to be a phosphoprotein with an apparent molecular mass of 56 kDa. In the presence of other viral proteins, p56 is converted into a slower-migrating form of NS5A (p58) by additional phosphorylation events. In this report, we show that the presence of NS3, NS4A, and NS4B together with NS5A is necessary and sufficient for the generation of the hyperphosphorylated form of NS5A (p58) and that all proteins must be encoded on the same polyprotein (in cis). Kinetic studies of NS5A synthesis and pulse-chase experiments demonstrate that fully processed NS5A is the substrate for the formation of p58 and that p56 is converted to p58. To investigate the role of NS3 in NS5A hyperphosphorylation, point and deletion mutations were introduced into NS3 in the context of a polyprotein containing the proteins from NS3 to NS5A. Mutation of the catalytic serine residue into alanine abolished protease activity of NS3 and resulted in total inhibition of NS5A hyperphosphorylation, even if polyprotein processing was allowed by addition of NS3 and NS4A in trans. The same result was obtained by deletion of the first 10 or 28 N-terminal amino acids of NS3, which are known to be important for the formation of a stable complex between NS3 and its cofactor NS4A. These data suggest that the formation of p58 is closely connected to HCV polyprotein processing events. Additional data obtained with NS3 containing the 34 C-terminal residues of NS2 provide evidence that in addition to NS3 protease activity the authentic N-terminal sequence is required for NS5A hyperphosphorylation.
Different populations of macrophages use either the vitronectin receptor or the phosphatidylserine receptor to recognize and remove apoptotic cells (1992)

One of the key features associated with programmed cell death in many tissues is the phagocytosis of apoptotic bodies by macrophages. Removal of apoptotic cells occurs before their lysis, indicating that these cells, during the development of apoptosis, express specific surface changes recognized by macrophages. We have compared the mechanisms by which four different macrophage populations recognize apoptotic cells. Murine macrophages elicited into the peritoneal cavity with either of two different phlogistic agents were able to phagocytose apoptotic cells. This phagocytosis was inhibited by phosphatidylserine (PS), regardless of the species (human or murine) or type (lymphocyte or neutrophil) of the apoptotic cell. In contrast, the murine bone marrow macrophage, like the human monocyte-derived macrophage, utilized the vitronectin receptor, an alpha v beta 3 integrin, for the removal of apoptotic cells, regardless of their species or type. That human macrophages are capable, under some circumstances, of recognizing PS on apoptotic cells was suggested by the observation that PS liposomes inhibited phagocytosis by phorbol ester-treated THP-1 cells. These results suggest that the mechanism by which apoptotic cells are recognized and phagocytosed by macrophages is determined by the subpopulation of macrophages studied.
X-ray diffraction study on the amorphous and crystalline components in bone mineral (1978)

[in Japanese]
Fish Consumption and Incidence of Diabetes (2012)

Accumulated evidence generated from this meta-analysis does not support an overall inverse association of fish or fish oil intake with incidence of diabetes. The null association was modified by study location (Eastern vs. Western countries), which may reflect the possible difference between Eastern and Western dietary patterns. Further studies are warranted.
p16ink4a and HPV L1 Immunohistochemistry is Helpful for Estimating the Behavior of Low-grade Dysplastic Lesions of the Cervix Uteri (2008)

As only a minority of low-grade dysplastic lesions of the cervix uteri will eventually progress to carcinoma, predicting the behavior of these lesions could be of high value in clinical practice. The aim of the study was to evaluate p16 ink4a and L1 as immunohistochemical markers of the biologic potentiality of low-grade dysplasia of the uterine cervix. The study included 38 conization specimens with coexisting cervical intraepithelial neoplasia grade 1 (CIN1) and 3 (CIN3) (group A) and 28 punch biopsies from women with CIN1 and proven spontaneous regression in the follow-up (group B). In group A, all CIN3 were p16 ink4a positive (p16+) and L1 negative (L1-). The CIN1 of this group were p16+L1- and p16+L1+ in 68.42% and 31.57%, respectively. No other expression pattern was found in this group. In group B, the p16+L1-, p16+L1+, p16-L1+, and p16-L1- patterns were found in 3.57%, 25%, 14.29%, and 57.14%, respectively. Overall, 96.29% p16+L1- CIN1 were found in group A, whereas all the p16-L1+ and p16-L1- CIN1 were found in group B. A significant difference between staining pattern distributions of group A and B was observed (P<0.0001). The results of the study show that p16 ink4a and L1 immunohistochemistry can be helpful for estimating the biologic potentiality of low-grade squamous cervical lesions. Particularly in cases in which the grade of the lesion is morphologically difficult to assess, the p16/L1 expression pattern could be useful for planning the clinical management of these women.
Collagen Triple Helix Formation Can Be Nucleated at Either End (2003)

The directional dependence of folding rates for rod-like macromolecules such as parallel alpha-helical coiled-coils, DNA double-helices, and collagen triple helices is largely unexplored. This is mainly due to technical difficulties in measuring rates in different directions. Folding of collagens is nucleated by trimeric non-collagenous domains. These are usually located at the COOH terminus, suggesting that triple helix folding proceeds from the COOH to the NH(2) terminus. Evidence is presented here that effective nucleation is possible at both ends of the collagen-like peptide (Gly-Pro-Pro)(10), using designed proteins in which this peptide is fused either NH(2)- or COOH-terminal to a nucleation domain, either T4-phage foldon or the disulfide knot of type III collagen. The location of the nucleation domain influences triple-helical stability, which might be explained by differences in the linker sequences and the presence or absence of repulsive charges at the carboxyl-terminal end of the triple helix. Triple helical folding rates are found to be independent of the site of nucleation and consistent with cis-trans isomerization being the rate-limiting step.
Protease-activated receptors (PARs)—biology and role in cancer invasion and metastasis (2015)

Although many studies have demonstrated that components of the hemostatic system may be involved in signaling leading to cancer progression, the potential mechanisms by which they contribute to cancer dissemination are not yet precisely understood. Among known coagulant factors, tissue factor (TF) and thrombin play a pivotal role in cancer invasion. They may be generated in the tumor microenvironment independently of blood coagulation and can induce cell signaling through activation of protease-activated receptors (PARs). PARs are transmembrane G-protein-coupled receptors (GPCRs) that are activated by a unique proteolytic mechanism. They play important roles in vascular physiology, neural tube closure, hemostasis, and inflammation. All of these agents (TF, thrombin, PARs-mainly PAR-1 and PAR-2) are thought to promote cancer invasion and metastasis at least in part by facilitating tumor cell migration, angiogenesis, and interactions with host vascular cells, including platelets, fibroblasts, and endothelial cells lining blood vessels. Here, we discuss the role of PARs and their activators in cancer progression, focusing on TF- and thrombin-mediated actions. Therapeutic options tailored specifically to inhibit PAR-induced signaling in cancer patients are presented as well.
Structure-independent DNA amplification by PCR using 7-deaza-2'-deoxyguanosine (1988)

Journal Article Structure-independent DNA amplification by PCR using 7-deaza-2'-deoxyguanosine Get access Lisa McConlogue, Lisa McConlogue Search for other works by this author on: Oxford Academic PubMed Google Scholar Mary Ann D. Brow, Mary Ann D. Brow 1Microbial Genetics, Cetus Corporation1400 Fifty-Third Street, Emeryville, CA 94608, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Michael A. Innis Michael A. Innis * 1Microbial Genetics, Cetus Corporation1400 Fifty-Third Street, Emeryville, CA 94608, USA * To whom correspondence should be addressed Search for other works by this author on: Oxford Academic PubMed Google Scholar Nucleic Acids Research, Volume 16, Issue 20, 25 October 1988, Page 9869, https://doi.org/10.1093/nar/16.20.9869 Published: 25 October 1988 Article history Received: 26 August 1988 Published: 25 October 1988
Activation of the c-Jun N-terminal kinase pathway by a novel protein kinase related to human germinal center kinase (1997)

The c-Jun N-terminal kinase (JNK), or stress-activated protein kinase plays a crucial role in cellular responses stimulated by environmental stress and proinflammatory cytokines. However, the mechanisms that lead to the activation of the JNK pathway have not been elucidated. We have isolated a cDNA encoding a novel protein kinase that has significant sequence similarities to human germinal center kinase (GCK) and human hematopoietic progenitor kinase 1. The novel GCK-like kinase (GLK) has a nucleotide sequence that encodes an ORF of 885 amino acids with 11 kinase subdomains. Endogenous GLK could be activated by UV radiation and proinflammatory cytokine tumor necrosis factor alpha. When transiently expressed in 293 cells, GLK specifically activated the JNK, but not the p42/44(MAPK)/extracellular signal-regulated kinase or p38 kinase signaling pathways. Interestingly, deletion of amino acids 353-835 in the putative C-terminal regulatory region, or mutation of Lys-35 in the putative ATP-binding domain, markedly reduced the ability of GLK to activate JNK. This result indicates that both kinase activity and the C-terminal region of GLK are required for maximal activation of JNK. Furthermore, GLK-induced JNK activation could be inhibited by a dominant-negative mutant of mitogen-activated protein kinase kinase kinase 1 (MEKK1) or mitogen-activated protein kinase kinase 4/SAPK/ERK kinase 1 (SEK1), suggesting that GLK may function upstream of MEKK1 in the JNK signaling pathway.
Expression of Hox-2.4 homeobox gene directed by proviral insertion in a myeloid leukemia (1989)

The presence of an altered Hox-2.4 gene in the WEHI3B murine myeloid leukemia suggests that homeobox genes may contribute to neoplasia. A survey of 31 leukemia cell lines of the myeloid, lymphoid and erythroid lineages revealed that Hox-2.4 was expressed only in WEHI3B and the pre-B lymphoid line 70Z/3, in which no DNA rearrangement was observed. To clarify the WEHI3B alteration and normal Hox-2.4 structure, we have sequenced near full length cDNA clones from WEHI3B and 70Z/3, and the 5' portion of the normal Hox-2.4 gene. A WEHI3B cDNA clone demonstrates that an intracisternal A-particle (IAP) provirus has inserted within the first exon of the gene and generated a Hox-2.4 mRNA with a 5' sequence derived from the IAP long terminal repeat. A remarkable degree of similarity found between the amino acid sequences of Hox-2.4 and Hox-3.1, which reside on different chromosomes, supports the notion that an ancient homeobox gene cluster has been duplicated and dispersed early in vertebrate evolution.
Current and Emerging Treatments for Multiple Myeloma (2008)

Major advancements in the diagnosis, staging, and treatment of myeloma offer promise in the future for changing MM from a terminal illness into a chronic, manageable condition.
Neuromodulation Techniques for the Treatment of the Overactive Bladder (2002)

Division of Urogynecology, Harvard Medical School, Cambridge, Massachusetts Correspondence: Neeraj Kohli, MD, 300 Mount Auburn Street, Suite 302, Cambridge, MA 02138. E-mail: [email protected]