gebhart/patrepeval huggingface dataset:
Two similar but nonallelic rat pancreatic trypsinogens. Nucleotide sequences of the cloned cDNAs. (1982)

We have cloned and identified mRNA sequences for two rat pancreatic trypsinogens. Nucleotide sequence analysis of the cloned sequences revealed two mRNAs that encode similar, though noallelic, pretrypsinogens. Trypsinogen I mRNA is 804 nucleotides in length, plus an estimated poly(A) tract of 100 nucleotides, and contains a short (13 nucleotide) 5' noncoding region and a 3' noncoding region of 54 nucleotides. It encodes a preproenzyme of 246 amino acids comprising a hydrophobic prepeptide (signal peptide) of 15 amino acids, an activation peptide characteristic of trypsinogens, and an active form of trypsin, 223 amino acids in length, that has 78% amino acid sequence identity with porcine trypsin. Trypsinogen II mRNA has a nucleotide sequence 88% homologous with that of trypsinogen I mRNA and encodes a protein with 89% amino acid sequence identity with trypsinogen I. The enzymes encoded by trypsinogen I and II mRNAs retain the key amino acid residues that determine the characteristic substrate cleavage preference of trypsins and, therefore, represent the rat counterparts of this digestive enzyme. Trypsinogen I mRNA is a major pancreatic mRNA comprising an estimated 2-5% of the total, whereas trypsinogen II mRNA is present at much lower levels.
Aluminium complexes of N,N′-ethylenebis(salicylideneimine)(H2salen). X-Ray crystal structures of [{Al(salen)}2(µ-O)]·MeCN and [Al(OC6H2Me3-2,4,6)(salen)] (1991)

The reaction of AlMe3 with H2salen [N,N′-ethylenenbis(salicylideneimine)] in MeCN gives the five-co-ordinate aluminium complex [AlMe(salen)]1. The interaction of 1 with H2O, HOPh, HOC6H4But-4, HOC6H2Me3-2,4,6, HO2CMe, HO2CPh, acetylacetone and 2-HOC6H4C(O)Me has been studied, and the X-ray structures of two of the products [{Al(salen)}2(µ-O)]·MeCN and [Al(OC6H2Me3-2,4,6)(salen)] have been determined. The proton and 27Al-{1H} NMR and IR spectra of the compounds have been recorded.
neu/erbB-2 amplification identifies a poor-prognosis group of women with node-negative breast cancer. Toronto Breast Cancer Study Group. (1998)

neu/erbB-2 amplification is an independent prognostic factor for risk of recurrence in ANN breast cancer. Women with tumors without neu/erbB-2 amplification have a good prognosis; aggressive therapy in this group is therefore difficult to justify. On the other hand, even with adjuvant chemotherapeutic treatment, women whose tumors exhibit neu/erbB-2 amplification have an increased risk of recurrence. We encourage a randomized trial to compare more aggressive adjuvant chemotherapy versus standard chemotherapy for ANN women whose tumors exhibit neu/erbB-2 amplification.
Heterogeneity of clonogenic cells in acute myeloblastic leukemia. (1985)

The expression of differentiation-associated surface antigens by the clonogenic leukemic cells from 20 patients with acute myeloblastic leukemia (AML) was studied with a panel of seven cytotoxic monoclonal antibodies (anti-Ia, -MY9, -PM-81, -AML-2-23, -Mol, -Mo2, and -MY3). The surface antigen phenotypes of the clonogenic cells were compared with the phenotypes of the whole leukemic cell population, and with the phenotypes of normal hematopoietic progenitor cells. In each case the clonogenic leukemic cells were found within a distinct subpopulation that was less "differentiated" than the total cell population. Clonogenic leukemic cells from different patients could be divided into three phenotype groups. In the first group (7 of 20 cases), the clonogenic cells expressed surface antigens characteristic of the normal multipotent colony-forming cell (Ia, MY9). These cases tended to have "undifferentiated" (FAB M1) morphology, and the total cell population generally lacked expression of "late" monocyte antigens such as MY3 and Mo2. A second group (seven cases) of clonogenic cells expressed surface antigens characteristic of an "early" (day 14) colony-forming unit granulocyte-monocyte (CFU-GM), and a third group (six cases) was characteristic of a "late" (day 7) CFU-GM. The cases in these latter two groups tended to have myelomonocytic (FAB M4) morphology and to express monocyte surface antigens. These results suggest that the clonogenic cells are a distinct subpopulation in all cases of AML, and may be derived from normal hematopoietic progenitor cells at multiple points in the differentiation pathway. The results further support the possibility that selected monoclonal antibodies have the potential to purge leukemic clonogenic cells from bone marrow in some AML patients without eliminating critical normal progenitor cells.
Clostridium botulinum Type F: Isolation from Venison Jerky (1972)

A Clostridium botulinum type F was isolated from the venison jerky responsible for the only type F botulism outbreak reported in the United States. The isolate differed from the prototype Langeland type F strain in being nonproteolytic.
Availability of cysteine and of L‐2‐oxo‐thiazolidine‐4‐carboxylic acid as a source of cysteine in intravenous nutrition (1990)

Cysteine is usually not included in amino acid solutions for intravenous nutrition for two reasons: it is not considered to be an essential amino acid, and it causes stability problems in solutions. The cysteine content of a solution decreases markedly in the presence of oxygen and/or glucose due to formation of various derivatives, such as cystine and D-glucocysteine. It is not clear if the formed derivatives are available for metabolic processes. A cysteine analogue, L-2-oxothiazolidine-4-carboxylic acid (OTCA), is stable in solutions and can be metabolized in the body-yielding cysteine. The metabolic availability of cysteine and OTCA from an all-in-one total parenteral nutrition (TPN) mixture was evaluated in the rat and compared to a regimen with cysteine infused from a separate container. A cysteine-free TPN mixture served as a control. All mixtures contained a suboptimal amount of methionine, which can normally be metabolized to cysteine, to enhance the nutritional effect of cysteine or OTCA supplement. The cysteine content in the admixture decreased approximately 40% during 30 hr after mixing. Nevertheless the utilization of this admixture was identical to the regimen supplying cysteine separately. The admixture containing OTCA showed similar results as the two cysteine regimens. All three regimens promoted growth significantly better than the cysteine-free-mixture. The results suggest that 1) cysteine is available for metabolic processes from its derivatives formed in an all-in-one TPN mixture, and 2) OTCA acts as a precursor of cysteine to the rat when supplied as a part of TPN.
Preparation and reactions of cyclic α-monocarbonyl azo-compounds: 1-pyrazolin-3-one derivatives (1970)

1-Pyrazolin-3-one (Ia) and its 5,5-dimethyl derivative (Ib) were prepared in good yield by oxidation of the corresponding pyrazolidin-3-one derivatives (Va) and (Vb) with lead tetra-acetate at low temperature. Reactions of (Ia and b) with various nucleophiles were examined. Hydroxide, alkoxides, alcohols, and amines attack initially at the carbonyl carbon atom; ring cleavage then gives intermediate carbanions (III), which are either protonated to yield propionic and isovaleric acid derivatives (VII)–(XII), or react with unchanged (Ia or b) to yield 1- and 2-substituted pyrazolidin-3-one derivatives, (XIII)–(XX). In the case of (Ia), considerable amounts of polymeric products are formed. Compound (Ia) is isomerised quantitatively by triethylamine to 2-pyrazolin-5-one (VI) even at low temperature. Carbanions from reagents such as ethylmagnesium bromide, and the enolate derived from 6-methoxy-1-tetralone, seem to attack (Ia and b) at various positions, giving complex mixtures of products; the 1-ethylpyrazolidin-3-ones (XXIIIa and b), and 2-(3-hydroxy-5,5-dimethyl-1-pyrazolin-3-yl)-6-methoxy-1-tetralone (XXVII), were isolated in considerable yields. With boron trifluoride–ether complex, (Ia and b) were converted into pyrazolidin-3-one derivatives (XL) and (XLII) in good yield.
The genetics of psoriasis, psoriatic arthritis and atopic dermatitis (2004)

Psoriasis and atopic dermatitis are chronic and relapsing inflammatory diseases of the skin associated with various immunologic abnormalities. Approximately 30% of psoriasis patients also have joint involvement, indicative of psoriatic arthritis. Genes and environment play a key role in the pathogenesis of these diseases. Genome-wide linkage scans have identified multiple loci linked to each disease and revealed overlap with psoriasis and atopic dermatitis susceptibility loci on chromosomes 1q21, 3q21, 17q25 and 20p12. The genes from these loci have not yet all been identified, or systematically tested for a role in psoriasis and atopic dermatitis; however, these locations suggest that some susceptibility factors lie within genes or gene families with common effects upon epithelial immunity. A strong HLA association is described for psoriasis, but not for atopic dermatitis. Knowledge of the genetic factors leading to these diseases will lead to an understanding of their variable age at onset, their waxing and waning and the variability of body surface environment. The effect of environmental triggers may also be understood once the altered pathways are elucidated. Genes implicated so far in atopic dermatitis are SPINK5, FcepsilonRI-beta and PHF11. Genes implicated in psoriasis so far are HLA-C, SLC9A3R1, NAT9, RAPTOR and SLC12A8. Genetic modifiers such as CARD15 may predispose to psoriatic arthritis.
Mind over immunity (2001)

The central nervous system regulates the innate immune system by elaborating anti-inflammatory hormone cascades in response to bacterial products and immune mediators. We recently discovered that the central nervous system also responds via acetylcholine-mediated efferent signals carried through the vagus nerve. Nicotinic cholinergic receptors expressed on macrophages detect these signals and respond with a dampened cytokine response. Vagus nerve stimulators can mimic this response and can prevent lethal endotoxemia. This newly appreciated cholinergic anti-inflammatory pathway provides a neural substrate to study brain-immune interactions and might be harnessed for therapy of cytokine-mediated disease.
A Global PHR (2007)

Our department was fortunate to receive an educational grant from InterComponentWare, AG (ICW), a leading international e-health company headquartered in Germany. For the past two years, we have been working with the corporate leadership of ICW as they begin to enter the US domestic marketplace. ICW “develops and markets software and hardware components for healthcare IT infrastructure for electronic health cards, personal health record known as LifeSensor® and network solutions for clinics and physicians in private practice.” ICW and its LifeSensor® PHR is the leading product in Germany, Austria, Switzerland and Bulgaria. With the help of a nationally prominent advisory board convened by our department, including such domestic luminaries as Janet Marchibroda from e-Health Initiative and Blackford Middleton from Partners Health Care System, Inc., the goal of our work is not only to help ICW to break into the domestic US market, but rather to expand their world view, suggest a research agenda, and network internationally.
Control of junB and extracellular matrix protein expression by transforming growth factor-beta 1 is independent of simian virus 40 T antigen-sensitive growth-sensitive growth-inhibitory events. (1991)

Treatment of Mv1Lu mink lung epithelial cells with transforming growth factor-beta 1 (TGF-beta 1) prevents phosphorylation of the retinoblastoma susceptibility gene product, RB, in late G1 phase of the cell cycle, which is thought to retain RB in a growth-suppressive state. This effect is paralleled by cell cycle arrest in late G1 (M. Laiho, J. A. DeCapric, J. W. Ludlow, D. M. Livingston, and J. Massagué, Cell 62:175-185, 1990). Arrest can be prevented by expression of simian virus 40 T antigen, which binds to underphosphorylated RB, presumably blocking its growth-suppressive activity. The response of cells to TGF-beta 1, however, is complex and includes changes in the levels of expression of genes encoding nuclear transcription factors and extracellular matrix components. To define the relationships among various components of the TGF-beta 1 response, we have investigated the effect of TGF-beta 1 on cells whose growth-inhibitory response to this factor is prevented by T antigen. TGF-beta 1 addition to exponentially growing Mv1Lu cells increased the levels of junB mRNA and of three extracellular matrix proteins: plasminogen activator inhibitor-1, fibronectin, and thrombospondin. Kinetically, the effects on junB and plasminogen activator inhibitor-1 expression occurred faster (half-maximal at 1 to 2 h) than the effects on fibronectin and thrombospondin expression (half-maximal at 6 to 10 h). These effects either preceded or overlapped, respectively, the withdrawal of Mv1Lu cells from the cell cycle. Expression of a transfected T-antigen gene in Mv1Lu cells, however, did not prevent any of these responses to TGF-beta 1. The results indcate that TGF-B1-stimulated expression of junB and extracellular matrix proteins in Mv1Lu cells can occur independently of the T-antigen-sensitive events that lead to growth arrest.
[Renal oncocytoma. Report of 13 cases]. (1997)

We report 13 cases of renal oncocytoma. Urinary symptoms occurred in only 3 cases. The patient's age ranged from 41 to 74 years with an average of 62.3 years. The mean tumor diameter was 5.6 cm (range: 1.5-14). Diagnostic features of ultrasonography, CT scan and, in some instances, angiography were suggestive of renal oncocytoma in 2 patients, but never affirmative, 4 patients were treated by partial nephrectomy. No local or metastatic recurrence was observed with a mean follow-up of 30.8 months, ranging from 6 to 96 months. We assume that the term renal oncocytoma should be restricted to tumors exclusively composed of regular oncocytic cells with an eosinophilic granular mitochondria-rich cytoplasm and an absence of malignant potential. Diagnostic imaging characteristics may sometimes suggest the diagnosis of renal oncocytoma, but cannot eliminate the main differential diagnosis, i.e. granular renal cell adenocarcinoma. When the tumor is small and unifocal, nephron sparing surgery may be considered. Whether or not the diagnosis has been confirmed by fine needle aspiration, conservative surgery must be controlled by intraoperative frozen sections of the tumor and surgical margins.
Synthesis of New Alkylaminooxysterols with Potent Cell Differentiating Activities: Identification of Leads for the Treatment of Cancer and Neurodegenerative Diseases (2009)

We describe here the syntheses and the biological properties of new alkylaminooxysterols. Compounds were synthesized through the trans-diaxial aminolysis of 5,6-alpha-epoxysterols with various natural amines including histamine, putrescine, spermidine, or spermine. The regioselective synthesis of these 16 new 5alpha-hydroxyl-6beta-aminoalkylsterols is presented. Compounds were first screened for dendrite outgrowth and cytotoxicity in vitro, and two leads were selected and further characterized. 5alpha-Hydroxy-6beta-[2-(1H-imidazol-4-yl)ethylamino]cholestan-3beta-ol, called dendrogenin A, induced growth control, differentiation, and the death of tumor cell lines representative of various cancers including metastatic melanoma and breast cancer. 5alpha-Hydroxy-6beta-[3-(4-aminobutylamino)propylamino]cholest-7-en-3beta-ol, called dendrogenin B, induced neurite outgrowth on various cell lines, neuronal differentiation in pluripotent cells, and survival of normal neurones at nanomolar concentrations. In summary, we report that two new alkylaminooxysterols, dendrogenin A and dendrogenin B, are the first members of a class of compounds that induce cell differentiation at nanomolar concentrations and represent promising new leads for the treatment of cancer or neurodegenerative diseases.
Chemotherapy-induced antitumor immunity requires formyl peptide receptor 1 (2015)

Antitumor immunity driven by intratumoral dendritic cells contributes to the efficacy of anthracycline-based chemotherapy in cancer. We identified a loss-of-function allele of the gene coding for formyl peptide receptor 1 (FPR1) that was associated with poor metastasis-free and overall survival in breast and colorectal cancer patients receiving adjuvant chemotherapy. The therapeutic effects of anthracyclines were abrogated in tumor-bearing Fpr1(-/-) mice due to impaired antitumor immunity. Fpr1-deficient dendritic cells failed to approach dying cancer cells and, as a result, could not elicit antitumor T cell immunity. Experiments performed in a microfluidic device confirmed that FPR1 and its ligand, annexin-1, promoted stable interactions between dying cancer cells and human or murine leukocytes. Altogether, these results highlight the importance of FPR1 in chemotherapy-induced anticancer immune responses.
Lymphadenopathy, elevated serum IgE levels, autoimmunity, and mast cell accumulation in flaky skin mutant mice (1998)

The autosomal recessive mutation "flaky skin" (fsn) causes pleiotropic abnormalities in the immune and hematopoietic systems accompanied by pathologic changes in the skin. Homozygotes (fsn/fsn) showed increased size and histological alterations in the spleen and lymph nodes. Abnormalities in lymphoid architecture of the spleen in fsn/fsn mice were accompanied by marked increases in total numbers of B cells, macrophages, and immature erythroid cells. Splenic B cells displayed elevated MHC class II expression. Serum IgE levels were greater than 100 microg/ml by 10 weeks of age, representing > 7000-fold increase compared with normal littermates. This increased IgE level was associated with elevated IL-4 production by spleen cells and with increased amounts of serum IL-4. Serum IgM, IgG1, and IgG2b levels were also increased in fsn/fsn mice while IgG3 was decreased. Autoimmunity in fsn/fsn mice was evidenced by glomerulonephritis accompanied by immune complex deposition in the kidneys, increased serum blood urea nitrogen levels, and the presence of circulating anti-double-stranded DNA autoantibodies. Pathological changes in the skin of fsn/fsn mice were characterized by epidermal hyperplasia and mixed dermal inflammation. Increased numbers of mast cells were also observed in the dermis of the truncal skin as well as in the epithelial stomach. These marked immunological abnormalities suggest that the fsn locus encodes a major immunoregulatory molecule important in multiple immune and hematopoietic functions.
Structural basis for serpin inhibitor activity (1995)

The mechanism of formation and the structures of serpin-inhibitor complexes are not completely understood, despite detailed knowledge of the structures of a number of cleaved and uncleaved inhibitor, noninhibitor, and latent serpins. It has been proposed from comparison of inhibitor and noninhibitor serpins in the cleaved and uncleaved forms that insertion of strand s4A into preexisting beta-sheet A is a requirement for serpin inhibitor activity. We have investigated the role of this strand in formation of serpin-proteinase complexes and in serpin inhibitor activity through homology modeling of wild type inhibitor, mutant substrate, and latent serpins, and of putative serpin-proteinase complexes. These models explain the high stability of the complexes and provide an understanding of substrate behavior in serpins with point mutations in s4A and of latency in plasminogen activator inhibitor I.
Homology Modeling Using Multiple Molecular Dynamics Simulations and Docking Studies of the Human Androgen Receptor Ligand Binding Domain Bound to Testosterone and Nonsteroidal Ligands (2001)

To facilitate the rational design of novel and more potent androgen receptor ligands, three-dimensional models for the human androgen receptor ligand binding domain bound to testosterone have been developed. These models of the androgen receptor were based on the crystal structure of the highly homologous human progesterone receptor ligand binding domain. The homology modeled androgen receptor was refined using unrestrained multiple molecular dynamics simulations in explicit solvent. Key H-bonding partners with the 17-hydroxy group and 3-keto group of testosterone are Asn705 and Thr877, and Gln711 and Arg752, respectively. These models show the presence of a unique unoccupied cavity within the androgen receptor binding pocket which may be valuable in the development of novel selective androgen receptor ligands. A qualitative analysis of amino acid mutations within the hAR binding pocket that affect ligand binding are consistent with these androgen receptor models. In addition to testosterone, the binding modes of several hydroxyflutamide-like nonsteroidal ligands for the androgen receptor are investigated using flexible docking with FlexX followed by refinement of the initial complexes with molecular dynamics simulations. These docking studies indicate that Asn705 is an important determinant in binding hydroxyflutamide and its derivatives by participating in H-bond interactions with the alpha-hydroxy moiety of these ligands. In addition, the nitro functionality mimics the 3-keto group of the natural ligand testosterone and is involved in H-bonding interactions with Gln711 and Arg752. From these docking studies, we suggest a mechanism for the enantioselective binding of chiral hydroxyflutamide derivatives and expand upon the previously reported structure-activity relationship for hydroxyflutamide and its derivatives.
Hormone Replacement Therapy and the Risk of Invasive Epithelial Ovarian Cancer in Swedish Women (2002)

Ever users of ERT and HRTsp but not HRTcp may be at increased risk of EOC.
Viscosities of vegetable oils and fatty acids (1992)

Data for viscosity as a function of temperature from 24 to 110°C (75 to 230°F) have been measured for a number of vegetable oils (crambe, rapeseed, corn, soybean, milk‐weed, coconut, lesquerella) and eight fatty acids in the range from C 9 to C 22 . The viscosity measurements were performed according to ASTM test methods D 445 and D 446. Several correlations were fitted to the experimental data. Correlation constants for the best fit are presented. The range of temperature in which the correlations are valid is from 24°C (75°F), or the melting point of the substance, to 110°C (230°F). The correlation constants are valuable for designing or evaluating such chemical process equipment as heat exchangers, reactors, distillation columns, mixing vessels and process piping.
Spontaneous Magnetic Flux and Quantum Noise in a Doubly Connected Mesoscopic SND Junction (1997)

We consider spontaneous magnetic flux in a doubly connected s-wave/normal metal/ d-wave superconductor (SND) Josephson junction. The flux magnitude is not quantized and is determined by the parameters of the system. In an isolated system, quantum fluctuations of the superconducting phase take place, leading to quantum flux noise. The possibilities of experimental observation of the effect are discussed.
Validation of an Integrated Staging System Toward Improved Prognostication of Patients With Localized Renal Cell Carcinoma in an International Population (2003)

A clinical algorithm that uses only 3 prognostic variables (1997 T stage, Fuhrman grade and performance status) to stratify patients with localized renal cell carcinoma into 3 risk groups has been shown to be applicable to external databases. This algorithm may be useful for patient counseling, surveillance and identification of high risk patients for enrollment in clinical trials.