Miracle-dz/UniFAR-FTUs huggingface dataset:
Effects of trastuzumab on epidermal growth factor receptor‐dependent and ‐independent human colon cancer cells

Little information is available as to the potential role of HER‐2 as a therapeutic target in colon cancers, which express much fewer HER‐2 receptors than breast cancer cells. Treatment of certain human colon cancer cell lines with the HER‐2 inhibitory antibody mAb 4D5 demonstrated a role for HER‐2 in mediating proliferation, apoptosis and tumorigenicity. However, only the cell lines that were dependent on autocrine EGFR‐mediated cell proliferation were susceptible to the antiproliferative and antitumorigenic effects of HER‐2 inhibition. The relative levels of HER‐2, EGFR, HER‐3 and HER‐4 were not predictive of responsiveness to mAb 4D5. Treatment with HER‐2 antibodies caused a decrease in HER‐2 protein levels in all of the colon cancer cell lines and also significantly decreased EGFR levels but only in the EGFR‐dependent cell lines. Treatment with mAb 4D5 caused the rapid ubiquitination and ligand‐dependent downregulation of the EGFR in an EGFR‐dependent colon cancer cell line. Treatment of athymic mice engrafted with EGFR‐dependent colon cancer cells with mAb 4D5 caused tumor regression and a decrease in EGFR tyrosine phosphorylation in the tumor cells. EGFR‐independent colon cancer cell xenografts were resistant to mAb 4D5 therapy. Combined inhibition of HER‐2 and EGFR caused large areas of necrosis in EGFR‐dependent colon cancer xenografts, suggesting a benefit of combined HER‐2 and EGFR inhibitor therapy. Predicting clinical responsiveness of human colon cancer cells to anti‐HER‐2 and anti‐EGFR therapy may require demonstration of EGFR tyrosine kinase dependency of the cells. © 2003 Wiley‐Liss, Inc.
Activation of the LicT Transcriptional Antiterminator Involves a Domain Swing/Lock Mechanism Provoking Massive Structural Changes*

The transcriptional antiterminator protein LicT regulates the expression of Bacillus subtilis operons involved in β-glucoside metabolism. It consists of an N-terminal RNA-binding domain (co-antiterminator (CAT)) and two phosphorylatable phosphotransferase system regulation domains (PRD1 and PRD2). In the activated state, each PRD forms a dimeric unit with the phosphorylation sites totally buried at the dimer interface. Here we present the 1.95 Å resolution structure of the inactive LicT PRDs as well as the molecular solution structure of the full-length protein deduced from small angle x-ray scattering. Comparison of native (inactive) and mutant (constitutively active) PRD crystal structures shows massive tertiary and quaternary rearrangements of the entire regulatory domain. In the inactive state, a wide swing movement of PRD2 results in dimer opening and brings the phosphorylation sites to the protein surface. This movement is accompanied by additional structural rearrangements of both the PRD1-PRD1 ′ interface and the CAT-PRD1 linker. Small angle x-ray scattering experiments indicate that the amplitude of the PRD2 swing might even be wider in solution than in the crystals. Our results suggest that PRD2 is highly mobile in the native protein, whereas it is locked upon activation by phosphorylation.
Normotensive sodium loading in normal man: regulation of renin secretion during beta-receptor blockade.

Saline administration may change renin-angiotensin-aldosterone system (RAAS) activity and sodium excretion at constant mean arterial pressure (MAP). We hypothesized that such responses are elicited mainly by renal sympathetic nerve activity by beta1-receptors (beta1-RSNA), and tested the hypothesis by studying RAAS and renal excretion during slow saline loading at constant plasma sodium concentration (Na+ loading; 12 micromol Na+.kg(-1). min(-1) for 4 h). Normal subjects were studied on low-sodium intake with and without beta1-adrenergic blockade by metoprolol. Metoprolol per se reduced RAAS activity as expected. Na+ loading decreased plasma renin concentration (PRC) by one-third, plasma ANG II by one-half, and plasma aldosterone by two-thirds (all P < 0.05); surprisingly, these changes were found without, as well as during, acute metoprolol administration. Concomitantly, sodium excretion increased indistinguishably with and without metoprolol (16 +/- 2 to 71 +/- 14 micromol/min; 13 +/- 2 to 55 +/- 13 micromol/min, respectively). Na+ loading did not increase plasma atrial natriuretic peptide, glomerular filtration rate (GFR by 51Cr-EDTA), MAP, or cardiac output (CO by impedance cardiography), but increased central venous pressure (CVP) by approximately 2.0 mmHg (P < 0.05). During Na+ loading, sodium excretion increased with CVP at an average slope of 7 micromol.min(-1). mmHg(-1). Concomitantly, plasma vasopressin decreased by 30-40% (P < 0.05). In conclusion, beta1-adrenoceptor blockade affects neither the acute saline-mediated deactivation of RAAS nor the associated natriuretic response, and the RAAS response to modest saline loading seems independent of changes in MAP, CO, GFR, beta1-mediated effects of norepinephrine, and ANP. Unexpectedly, the results do not allow assessment of the relative importance of RAAS-dependent and -independent regulation of renal sodium excretion. The results are compatible with the notion that at constant arterial pressure, a volume receptor elicited reduction in RSNA via receptors other than beta1-adrenoceptors, decreases renal tubular sodium reabsorption proximal to the macula densa leading to increased NaCl concentration at the macula densa, and subsequent inhibition of renin secretion.
CHARACTERIZATION OF ACID PHOSPHATASE AND PHOSPHORYLCHOLINE HYDROLASE IN ADULT HAEMONCHUS CONTORTUS

An acid phosphatase (AP) and a phosphorylcholine hydrolase (PCH) were detected in excretory–secretory (ESP) products from adult Haemonchus contortus. The AP had a pH optimum of 4.5 and was inhibited by tartaric acid and sodium fluoride, but not by o-phenanthroline. The AP hydrolyzed paranitrophenol (pnp)-phosphate and to a lesser extent pnp-phenylphosphonate but did not hydrolyze diester substrates. Purified AP consisted of heterodimers with relative molecular weight (Mr) of 41.9 and 48.7 kDa and had a native molecular weight of 98 kDa by size-exclusion chromatography (SEC). The PCH had a pH optimum of about 9.5 and was inhibited by EDTA and o-phenanthroline but not by the specific phospholipase inhibitor D609. The specific activity of PCH in the ESP was aproximately 25-fold less than that of AP. PCH also hydrolyzed 5′-thymidine monophosphate-pnp at a rate about 40% lower than pnp-phosphorylcholine but did not hydrolyze 3′-thymidine monophosphate-pnp. Partial purification of PCH suggests an Mr of 50.2 kDa by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and an Mr of 102 kDa by SEC. Both AP and PHC were secreted in vitro in a time-dependent manner and had their highest concentrations in the intestine. The results indicate that H. contortus adults secrete significant amounts of AP that might be a digestive enzyme. PCH is also an intestinal enzyme and is secreted in lesser amounts than AP. The PCH is probably not a phospholipase C but has some characteristics of a type I phosphodiesterase.
The Vibrio cholerae Pst2 Phosphate Transport System Is Upregulated in Biofilms and Contributes to Biofilm-Induced Hyperinfectivity

Volume 80, no. 5, p. 1794 –1802, 2012. Page 1794, column 2, lines 20 –23: “There are currently no data comparing the regulation of the pst and pst2 loci, and the regulatory connections between PhoB and pst2 have not been determined” should read “There are currently no data comparing the regulation of the pst and pst2 loci. The periplasmic component of the Pst2 system has been identified in a study comparing the proteomes of phosphate-starved wild-type and phoB mutant V. cholerae (43a), but the precise regulatory connections between PhoB and the pst2 locus have not been determined. ” Page 1802: The following reference was inadvertently omitted.
Developmental Rates at Constant Temperatures of Three Economically Important Ceratitis spp. (Diptera: Tephritidae) From Southern Africa

Abstract Three species of Ceratitis MacLeay are of economic importance in southern Africa. To learn more about the influence of temperature on the development of these species, the developmental rates of South African populations of Ceratitis (Ceratitis) capitata (Wiedemann), C. (Pterandrus) rosa Karsch, and C. (Ceratalaspis) cosyra (Walker) were compared at constant temperatures of 14, 18, 22, 26, and 30°C. The duration of each life stage and the percentage survival of the immature life stages of each species were determined. One linear and three nonlinear developmental rate models (Briére, Lactin, and Logan-6) were found to fit the data well and were used to generate the minimum, optimum, and maximum developmental thresholds, in addition to the life cycle thermal constants for the three species. These parameter values were 9.6, 28.5, 33.0, and 338 for C. capitata, 9.7, 28.8, 33.2, and 376 for C. cosyra, and 8.6, 27.7, 33.0, and 429 for C. rosa, respectively. The parameters for C. capitata are similar to those found by other researchers for this species in Reunion but the parameters for C. rosa differ substantially from published values for a Reunion population of this species, suggesting that these are different biotypes. The similarities between the developmental parameters for C. capitata and C. cosyra do not support known differences in the distribution of these species so other limiting factors such as relative humidity and the availability of host species may be important. This finding therefore cautions against basing predictions of potential global distributions of species solely on life table or climatic parameter values.
The Information Content of Market-on-Close Imbalances, the Specialist and NYSE Equity Prices

We examine the relationship between announcements of (a) market-on-close orders, (b) the price dynamics and (c) specialist trading on the New York Stock Exchange. We find that the closing order imbalance affects prices even prior to the announcement of the imbalance. This is consistent with investors expressing their demands through both market-on-close orders and direct purchases - so that some of the price impact could occur before the specialist's announcement of the imbalance. However, the specialist himself is trading prior to the announcement, which also helps explain why at least some of the price movement occurs before the dissemination of the imbalances. Consequently, the remaining investors are actually trading /against/ the direction of their closing imbalances and the specialist is /not/ helping to smooth investor demands. Because of the structure of the mechanism and the volatility of prices near the close (which is especially elevated at the deadline for market on close orders at 3:40 p.m.), this is an interesting context for studying how information gets reflected in price.
Crédito y financiamiento bancario ( Brasil y México)

<p align="right"> </p><p>El presente trabajo tiene como objetivo analizar el comportamiento del crédito y financiamiento en las economías de México y Brasil a partir del comienzo del siglo XXI, analizando las consecuencias de las modificaciones ejecutadas a sus sistemas bancarios en la década de los noventa. Examinando su función en momentos de crisis y recesión, en particular ante la crisis financiera global de 2007-2008. </p><p> </p><div><hr align="left" size="1" width="33%" /><div><p> </p></div></div>
A novel physiological function for platelet‐derived growth factor‐BB in rat dermis.

1. The present experiments describe a role for platelet‐derived growth factor‐BB and cellular adhesion receptors towards extracellular matrix molecules (beta 1‐integrins) in control of interstitial fluid pressure (Pif). 2. Pif was measured in rat skin with sharpened glass capillaries (3‐7 microns) connected to a servocontrolled counter‐pressure system. 3. The collagen and laminin‐binding alpha 2 beta 1‐integrin is involved in the control of Pif since subdermal injection (5 microliters) of monoclonal hamster anti‐rat alpha 2 beta 1‐integrin IgG (anti‐alpha 2 beta 1) resulted in increased negativity of Pif. Control Pif averaged ‐0.88 +/‐ 0.23 mmHg (+/‐ S.D.) and decreased to ‐2.50 +/‐ 0.35 mmHg (P < 0.05) and ‐3.88 +/‐ 1.45 mmHg (P < 0.05) at anti‐alpha 2 beta 1 concentrations of 0.56 and 1.12 mg ml‐1, respectively. 4. The effect of anti‐alpha 2 beta 1 was abolished when platelet‐derived growth factor‐BB (PDGF‐BB) (200 ng ml‐1) was injected together with anti‐alpha 2 beta 1. 5. The time‐ and dose‐responses of PDGF‐BB to counteract increased negativity of Pif were studied further using dextran anaphylaxis as an experimental model inducing increased negativity of Pif in skin. Control Pif averaged ‐0.33 +/‐ 0.43 mmHg and fell to ‐4.10 +/‐ 1.47 mmHg within 10 min after dextran (P < 0.01). Subsequent subdermal injection of PDGF‐BB at 200 ng ml‐1 normalized Pif in 10‐20 min which became ‐1.37 +/‐ 1.23 mmHg (P < 0.01 versus dextran, P > 0.05 versus control). PDGF‐BB had little or no effect at 50 ng ml‐1. PDGF‐AA and basic fibroblast growth factor had no effect on Pif. 6. The in vivo function reported for PDGF‐BB has not been described previously and provides further evidence for active participation of connective tissue cells in control of Pif by altering tension on extracellular matrix structures.
Continuous positive airway pressure for central sleep apnea and heart failure.

BACKGROUND The Canadian Continuous Positive Airway Pressure for Patients with Central Sleep Apnea and Heart Failure trial tested the hypothesis that continuous positive airway pressure (CPAP) would improve the survival rate without heart transplantation of patients who have central sleep apnea and heart failure. METHODS After medical therapy was optimized, 258 patients who had heart failure (mean age [+/-SD], 63+/-10 years; ejection fraction, 24.5+/-7.7 percent) and central sleep apnea (number of episodes of apnea and hypopnea per hour of sleep, 40+/-16) were randomly assigned to receive CPAP (128 patients) or no CPAP (130 patients) and were followed for a mean of two years. During follow-up, sleep studies were conducted and measurements of the ejection fraction, exercise capacity, quality of life, and neurohormones were obtained. RESULTS Three months after undergoing randomization, the CPAP group, as compared with the control group, had greater reductions in the frequency of episodes of apnea and hypopnea (-21+/-16 vs. -2+/-18 per hour, P<0.001) and in norepinephrine levels (-1.03+/-1.84 vs. 0.02+/-0.99 nmol per liter, P=0.009), and greater increases in the mean nocturnal oxygen saturation (1.6+/-2.8 percent vs. 0.4+/-2.5 percent, P<0.001), ejection fraction (2.2+/-5.4 percent vs. 0.4+/-5.3 percent, P=0.02), and the distance walked in six minutes (20.0+/-55 vs. -0.8+/-64.8 m, P=0.016). There were no differences between the control group and the CPAP group in the number of hospitalizations, quality of life, or atrial natriuretic peptide levels. An early divergence in survival rates without heart transplantation favored the control group, but after 18 months the divergence favored the CPAP group, yet the overall event rates (death and heart transplantation) did not differ (32 vs. 32 events, respectively; P=0.54). CONCLUSIONS Although CPAP attenuated central sleep apnea, improved nocturnal oxygenation, increased the ejection fraction, lowered norepinephrine levels, and increased the distance walked in six minutes, it did not affect survival. Our data do not support the use of CPAP to extend life in patients who have central sleep apnea and heart failure.
Vascular and Interstitial Changes in the Peritoneum of Capd Patients with Peritoneal Sclerosis

Objective To analyze morphological changes in the peritoneum of peritoneal sclerosis (PS) patients. Emphasis was put on vascular abnormalities, because the continuous exposure to glucose-based dialysis solutions could cause diabetiform changes and because longitudinal transport studies suggested the development of a large peritoneal vascular surface area. Design Peritoneal biopsies from continuous ambulatory peritoneal dialysis (CAPD) patients were investigated in two studies. Diabetic patients were excluded. In study 1, 11 PS biopsies were compared to three control groups varying in duration of CAPD treatment: 0 months (n = 15), 2 – 25 months (n = 7), and > 25 months CAPD (n = 7). The second study was a case-control study, comparing six biopsies from the long-term control group to six PS biopsies, matched for age and duration of CAPD. All biopsies were scored for presence and type of fibrosis [Picro Sirius red, type IV collagen, α-smooth muscle actin (αSMA)] and for neoangiogenesis (factor VIII). Thickening of vascular walls by type IV collagen and vasodilation of capillaries were measured by computer-aided planimetry. Results In study 1 the presence of sclerosing fibrosis, deposition of interstitial type IV collagen, and the number of myofibroblasts (αSMA-positive cells) was greater in the PS biopsies than biopsies from all control groups (p < 0.002). Moreover, the number of vessels per field was higher in PS biopsies (p < 0.01). Vascular wall thickening of small arteries (p < 0.008) and vasodilation of capillaries were found in PS biopsies compared to all control groups (p < 0.007). The second study revealed differences in the presence of sclerosis but not in the extent of fibrosis between PS biopsies and their controls. The number of vessels per field in PS biopsies was higher compared to controls (p = 0.04). Also, thickening of the vascular wall was more marked in PS biopsies (p = 0.03). Vasodilation of capillaries was greater in PS biopsies than in controls (p = 0.07). Conclusion Fibrosis of the peritoneum may precede peritoneal sclerosis. The deposition of type IV collagen and the presence of myofibroblasts in the interstitial layer could be part of a pathologic process similar to the scarring in diabetic nephropathy. Neoangiogenesis and thickening of the vascular wall by type IV collagen are consistent with glucose-induced microangiopathy. These abnormalities and the vasodilation of the capillaries can explain the high dialysate-to-plasma ratios or mass transfer area coefficients of low molecular weight solutes that can be found in long-term CAPD patients.
Distribution and significance of heterotrophic marine bacteria with antibacterial activity

Bacteria with antibacterial activity were isolated from seawater, sediments, phytoplankton, and zooplankton of Suruga, Sagami, and Tokyo Bays and from soft corals and sponges collected from the Taiwan coast. Of the 726 strains isolated, 37 showed antibacterial activity against either Vibrio parahaemolyticus (ATCC 17802) or Staphylococcus aureus (P209). Sediment harbored the lowest number of these forms of bacteria, and those from Tokyo Bay did not show any activity. Attached isolates showed greater activity compared with free-living forms. Relatively high numbers of strains with antibacterial activity were associated with phytoplankton. Among the zooplankton isolates, cladocerans harbored the maximum number of antibacterial strains. Isolates were more inhibitory to gram-positive test cultures. Autoinhibition was observed only among 8% of the isolates. Marine nonproducers were more susceptible. Pseudomonas/Alteromonas species made up 81.0% of isolates, of which 30% were pigmented strains. The absence or reduction in number of bacteria with antibacterial activity in Tokyo Bay is attributed to its eutrophic nature, which may tend to moderate the production of antibacterial compounds.
HTLV‐1 modifies the clinical and immunological response to schistosomiasis

The immunological response in HTLV‐1 infected individuals is characterized by a prominent Type‐1 cytokine response with high production of IFN‐γ and TNF‐α. In contrast, helminthic infections and in particular chronic schistosomiasis are associated with a predominant production of IL‐4, IL‐5, IL‐10 and IL‐13. Liver fibrosis is the main pathological finding in schistosomiasis that occurs after many years of infection. This pathology is T cell dependent but the immune response mechanisms are not completely understood. The North‐east region of Brazil is endemic for both HTLV‐1 and schistosomiasis. In the present study the immune response, clinical severity, and therapeutic response to praziquantel of patients with schistosomiasis coinfected with HTLV‐1 were compared with patients infected only with S. mansoni. Patients with HTLV‐1 and S. mansoni had lower levels of IL‐5 (P < 0·05) and higher levels of IFN‐γ (P < 0·05) in cultures stimulated with S. mansoni antigen and decreased S. mansoni antigen specific IgE levels when compared with patients with schistosomiasis without HTLV‐1 coinfection. Liver fibrosis was mild in all HTLV‐1 coinfected patients and efficacy of praziquantel was lower in patients dually infected than in patients infected only with S. mansoni.
Cardiovascular Function During Induced Hypotension by Fenoldopam or Sodium Nitroprusside in Anesthetized Dogs

Fenoldopam, a selective dopamine1 receptor agonist, has been recommended for induced hypotension because it effectively lowers arterial blood pressure and improves renal perfusion. We examined cardiovascular functions during hypotension induced by fenoldopam or sodium nitroprusside. In eight halothane-anesthetized dogs, the left ventricle (LV) was instrumented with pressure and ultrasonic dimension transducers for the assessment of LV contractility using the analysis of the pressure-diameter relationship. Blood flow distribution was measured by radioactive microspheres. Doses of fenoldopam and nitroprusside were titrated to reduce mean arterial blood pressure to 60 mm Hg. After 40 min of hypotension, fenoldopam and nitroprusside caused similar increases in heart rate (17% ± 4% vs 19% ± 10%, respectively) and decreases in systemic vascular resistance (−24% ± 5% vs-27% ± 4%). Hypotension induced by fenoldopam was associated with higher LV end-diastolic pressure (4.4 ± 0.6 vs 2.5 ± 1.1 mm Hg) and end-systolic meridional wall stress (33.0 ± 4.3 vs 17.8 ± 2.1 g/cm2) when compared with nitroprusside. There were no significant changes in cardiac output and cardiac contractility as expressed by the slope (Ees) of the LV end-systolic pressure-diameter relationship, velocity of shortening of the diameter, and percentage of wall thickening of the LV. In contrast to nitroprusside, which decreased renal blood flow from 197 ± 19 to 163 ± 15 mL/min, renal blood flow increased during fenoldopam-induced hypotension from 187 ± 20 to 239 ± 18 mL/min. The increase in renal perfusion was similar in upper, middle, and lower regions of the kidney; however, it was more in the medulla compared with the cortex (37% ± 17% vs 25% ± 7%). Both fenoldopam and nitroprusside decreased splenic blood flow, but neither altered flow to the brain, skin, or myocardium. Muscle and hepatic arterial blood flow were significantly less with fenoldopam than with nitroprusside. Fenoldopam was associated with significantly larger increases in plasma renin activity compared with nitroprusside. The results of this study show an increase in renal blood flow during fenoldopam infusion that may be of advantage particularly when renal hypoperfusion should be avoided.