Miracle-dz/UniFAR-FTUs huggingface dataset:
Disease-free survival was greater with letrozole than tamoxifen in postmenopausal women with early breast cancer.

M e t h o d s Design: Randomized controlled trial (Breast International Group [BIG] 1-98 study). Allocation: Concealed. * Blinding: Blinded {patients, clinicians, outcome assessors, data analysts, and data safety and monitoring committee}†. * Follow-up period: Median 26 months. Setting: Several hundred centers worldwide. Patients: 8028 postmenopausal women 38 to 90 years of age (median age 61 y) with invasive breast cancer positive for estrogen and/or progesterone receptors; primary surgery resulting in clear margins; and adequate hematologic, renal, and hepatic function. Exclusion criteria included evidence of metastatic disease and other cancer in the previous 5 years. Intervention: Letrozole, 2.5 mg daily (n = 4015), or tamoxifen, 20 mg daily (n = 4013), for 2 or 5 years. (Patients allocated to 2-y treatment received the alternate drug for the next 3 y but were censored 30 d after switching for this analysis). Outcomes: Disease-free survival (ended by any recurrence, new cancer in the contralateral breast or elsewhere in the body, or death), systemic disease-free survival (as above but excluding breast events), overall survival, and adverse events. Patient follow-up: 99.8% (intention-to-treat analysis).
Maximal human neutrophil priming for superoxide production and elastase release requires p38 mitogen-activated protein kinase activation.

HYPOTHESIS Neutrophil priming has been implicated in the development of multiple organ failure, although the precise intracellular mechanisms that regulate neutrophil priming remain unclear. Our previous work characterized platelet-activating factor (PAF) priming of human neutrophils for concordant superoxide anion (O2-) generation and elastase degranulation. The p38 mitogen-activated protein kinase (MAPK) is activated by PAF stimulation. We hypothesized that PAF-induced human neutrophil priming for O2- and elastase release is mediated via the p38 MAPK pathway. DESIGN Isolated neutrophils from 6 human donors were preincubated with the specific p38 MAPK inhibitor SB 203580 (1 micromol/L) or buffer (control) for 30 minutes. Cells were then primed with PAF (200 nmol/L), followed by receptor-dependent (N-formyl-methionyl-leucyl-phenylalanine, 1 micromol/L) or receptor-independent phorbol myristate acetate (PMA, 100 ng/mL) activation. SETTING Urban trauma research laboratory. PATIENTS Healthy volunteer donors of neutrophils. MAIN OUTCOME MEASURES Maximal rate of O2- generation was measured by superoxide dismutase-inhibitable reduction of cytochrome c and elastase release by the cleavage of N-methoxysuccinyl-Ala-Ala-Pro-Val-p-nitroanilide. RESULTS SB 203580 significantly attenuated the generation of O2- and release of elastase from neutrophils activated with N-formyl-methionyl-leucyl-phenylalanine but not with PMA. Independent of the activator receptor status, SB 203580 almost completely blocked the exaggerated neutrophil cytotoxic response due to PAF priming. CONCLUSIONS The p38 MAPK pathway is required for maximal PAF-induced neutrophil priming for O2- production and elastase degranulation. Therefore, the MAPK signaling cascade may offer a potential therapeutic strategy to preempt global neutrophil hyperactivity rather than attempt to nullify the end products independently.
The transmission and geographical spread of African horse sickness and bluetongue viruses.

African horse sickness virus (AHSV) and bluetongue virus (BTV) are dsRNA viruses within the genus Orbivirus. Both are able to cause non-contagious, infectious arthropod-borne diseases in their respective vertebrate hosts. AHSV infects equines and occasionally dogs, whereas BTV replicates in ruminants. The disease caused by AHSV is usually at its most severe in horses, whereas certain breeds of sheep are particularly sensitive to BTV infection. AHSV is endemic in sub-Saharan Africa but periodically makes brief excursions beyond this area. BTV occurs much more widely and can be found in a band around the World, stretching from approximately 40 degrees N to 35 degrees S. In the wild, both viruses are transmitted between their vertebrate hosts almost entirely via the bites of arthropod vectors, although dogs can occasionally acquire AHSV by eating virus-contaminated meat and BTV may be infrequently transmitted via infected semen or transplacentally. Because of their reliance upon arthropod vectors, BTV and AHSV have a global distribution which is limited not only by the requirement for susceptible vertebrates but also by the necessity for competent arthropod vectors. The major vectors of AHSV and BTV are certain species of Culicoides biting midge, which are true biological vectors but mosquitoes and/or ticks may also be involved to a greater or lesser extent. Until recently, AHSV has apparently been unable to survive beyond its traditional endemic zones in sub-Saharan Africa for more than 2-3 years at most. This has been interpreted as being due to a number of factors, including the absence of a long-term vertebrate reservoir, a lower prevalence, shorter, seasonal incidence and decreased transmission efficiency of the local vectors and also possibly to the effect of control measures (vector abatement, vaccination). The recent outbreaks of African horse sickness (AHS) in Spain, Portugal and Morocco, which persisted for at least 5 years (1987-1991) therefore seem to have established a new pattern in AHSV survival in an epidemic zone. This extended persistence may be due to the 'all-year-round' presence in the area of adult Culicoides imicola, the major AHSV vector. This is basically an Afro-Asiatic species and its continuous presence in parts of Iberia and may be due to some recent moderation in the climate. Further northerly extensions in the range of Culicoides imicola, in response to 'climatic moderation', cannot be ruled out and could substantially increase the area of Europe 'at risk' to AHS. (ABSTRACT TRUNCATED AT 400 WORDS)
SOME PARASITES AND DISEASES OF ESTUARINE FISHES IN POLLUTED HABITATS OF MISSISSIPPI *

Diseases that afflict aquatic animals living in waters suspected or known to be polluted are described. The following pollutants are discussed with regard to their effects on the environment and the animals of the estuaries; pesticides, industrial chemicals, heavy metals, and fecal pollution. Microorganisms are discussed with regard to public health and fish health. Transmission of the virus of infectious hepatitis by oysters is emphasized. Parasitic diseases are discussed with regard to life cycle of the parasite, effects of pollution on intermediate hosts, and host specificity. Diseases caused by various helminth and protozoan parasites are described. Nonparasitic diseases discussed are integumental hyperplasia, liver disease, and various neoplasms. (HLW)
Posttraining Intraamygdala Infusions of Oxotremorine and Propranolol Modulate Storage of Memory for Reductions in Reward Magnitude

These experiments examined the effects of posttraining intraamygdala administration of the muscarinic agonist, oxotremorine, and the beta-noradrenergic antagonist, propranolol, on memory for reduction in reward magnitude. Male Sprague-Dawley rats (175-200 g) implanted with bilateral intraamygdala cannulae were food deprived (maintained at 80% of body weight) and trained to run a straight alley (six trials/day) for either ten 45-mg food pellets (high reward) or one 45-mg food pellet (low reward) for 10 days. In Experiment One, the animals in the high-reward group were than shifted to a one-pellet reward and immediately given intraamygdala infusions (0.5 microliter/side) of either oxotremorine (10 ng) or phosphate buffer. Shifted training continued for 4 more days and no further injections were given. Shifted animals given the buffer solution displayed an increase in runway latencies but returned to preshift latencies by the fifth day of shifted training. In contrast, animals given oxotremorine exhibited increased latencies through the fifth day. In Experiment Two, rats were trained as in Experiment. One but immediately following the shift received intraamygdala infusions of oxotremorine (10 ng), propranolol (0.3 microgram), both, or phosphate buffer. Shifted vehicle-injected rats returned to preshift performance by the fifth day of shifted training. Shifted propranolol rats returned to preshift latencies by the third day of shifted training. In contrast, the shifted oxotremorine and the shifted oxotremorine/propranolol rats displayed longer latencies than unshifted controls through 5 days of shifted training. The findings indicate that the muscarinic cholinergic and beta-noradrenergic systems within the amygdala interact in regulating memory and support the view that noradrenergic influences are mediated through cholinergic activation.
A Dominant Interfering Bub1 Mutant Is Insufficient To Induce or Alter Thymic Tumorigenesis In Vivo, Even in a Sensitized Genetic Background

ABSTRACT Aneuploidy is a common feature of human tumors, often correlating with poor prognosis. The mitotic spindle checkpoint is thought to play a major role in aneuploidy suppression. To investigate the role of the spindle checkpoint in tumor suppression in vivo, we developed transgenic mice in which thymocytes express a dominant interfering fragment of Bub1, a kinase regulator of the spindle checkpoint. We report that, despite high-level expression of dominant-negative Bub1 (Bub1DN), a protein known to inhibit spindle checkpoint activity in cultured cells, thymocytes show no evidence of spindle checkpoint impairment. Transgenic animals also failed to show an increased predisposition to spontaneous tumors. Moreover, the Bub1DN transgene failed to alter the timing or characteristics of thymic lymphoma development in p53 heterozygous or homozygous null backgrounds, indicating that the lack of tumorigenesis is not due to suppression by p53-dependent checkpoints. These results indicate that overexpression of a Bub1 N-terminal fragment is insufficient to impair the spindle checkpoint in vivo or to drive tumorigenesis in the highly susceptible murine thymocyte system, either alone or in combination with G1 checkpoint disruption.
Optimization of Extraction Conditions of Phenolic Compounds from Pistachio ( Pistachia vera ) Green Hull through Response Surface Method

Phenolic compounds, especially those of plant origin, constitute an essential part of the human diet, and are of considerable interest due to their antioxidant properties. In this study, Ultrasound-Assisted Extraction (UAE), Microwave-Assisted Extraction (MAE), as well as Maceration Extraction (ME) methods were applied for phenolic compounds’ extraction from pistachio green hull. Response surface methodology was employed to optimize the extraction conditions as regards the yield of the compounds. A Central Composite Design (CCD) was employed to investigate the effects of three independent variables, namely liquid-to-solid ratio (8-20 times), temperature (25-65 °C) and time (5-45 minutes) on the dependent variable (level of total phenolic compounds). The results indicated that within the same extraction time, the extraction yield through UAE was higher than those in ME and MAE methods. Correlation coefficients (R 2 ) of the models for UAE, MAE and ME methods were 0.95, 0.96 and 0.94, respectively. The optimal conditions for extraction of phenolic compounds from pistachio green hull through ME, UAE, and MAE methods were 20(v/w), 65°C, 45 minutes; 20(v/w), 65°C, 25 minutes; and 20(v/w), 65°C, 45 minutes, respectively. Under optimized conditions the experimental values well agreed with the values predicted by the proposed models.
Monomeric Recombinant TCR Ligand Reduces Relapse Rate and Severity of Experimental Autoimmune Encephalomyelitis in SJL/J Mice through Cytokine Switch1

Our previous studies demonstrated that oligomeric recombinant TCR ligands (RTL) can treat clinical signs of experimental autoimmune encephalomyelitis (EAE) and induce long-term T cell tolerance against encephalitogenic peptides. In the current study, we produced a monomeric I-As/PLP 139-151 peptide construct (RTL401) suitable for use in SJL/J mice that develop relapsing disease after injection of PLP 139-151 peptide in CFA. RTL401 given i.v. or s.c. but not empty RTL400 or free PLP 139-151 peptide prevented relapses and significantly reduced clinical severity of EAE induced by PLP 139-151 peptide in SJL/J or (C57BL/6 × SJL)F1 mice, but did not inhibit EAE induced by PLP 178-191 or MBP 84-104 peptides in SJL/J mice, or MOG 35-55 peptide in (C57BL/6 × SJL/J)F1 mice. RTL treatment of EAE caused stable or enhanced T cell proliferation and secretion of IL-10 in the periphery, but reduced secretion of inflammatory cytokines and chemokines. In CNS, there was a modest reduction of inflammatory cells, reduced expression of very late activation Ag-4, lymphocyte function-associated Ag-1, and inflammatory cytokines, chemokines, and chemokine receptors, but enhanced expression of Th2-related factors, IL-10, TGF-β3, and CCR3. These results suggest that monomeric RTL therapy induces a cytokine switch that curbs the encephalitogenic potential of PLP 139-151-specific T cells without fully preventing their entry into CNS, wherein they reduce the severity of inflammation. This mechanism differs from that observed using oligomeric RTL therapy in other EAE models. These results strongly support the clinical application of this novel class of peptide/MHC class II constructs in patients with multiple sclerosis who have focused T cell responses to known encephalitogenic myelin peptides.
Perigranuloma localization and abnormal maturation of B cells: emerging key players in sarcoidosis?

RATIONALE Recent observations of abnormal immunoglobulin responses and case reports describing successful B-cell ablative therapy suggest involvement of B cells in the pathogenesis of sarcoidosis. OBJECTIVES To investigate how abnormal B-cell maturation and function in patients with sarcoidosis contribute to disease. METHODS Patients with sarcoidosis (n = 32) were included for detailed analysis by immunohistochemistry of tissue, flow cytometry of blood B-cell subsets, and serum immunoglobulin levels. Vaccination responses in patients with sarcoidosis to influenza virus and encapsulated bacteria and molecular analysis of immunoglobulin heavy chain transcripts were studied for functional analysis of immunoglobulin responses. MEASUREMENTS AND MAIN RESULTS Perigranuloma localization of IgA-producing plasma cells and numerous B cells were found in affected tissues. Total blood B-cell numbers were normal, CD27(+) memory B cells were significantly reduced, and CD27(-)IgA(+) B cells were significantly increased; the results are normalized in patients treated with TNF-α blockers. Despite this, patients had normal serum immunoglobulin levels and normal antigen-specific immunoglobulin responses. IgA and IgG transcripts, however, showed high frequencies of somatic hypermutations and increased usage of downstream IgG subclasses, suggestive for prolonged or repetitive responses. CONCLUSIONS The large B-cell infiltrates in granulomatous tissue and increased molecular signs of antibody maturation are indicative of direct involvement of B cells in local inflammatory processes in patients with sarcoidosis. Moreover, CD27(-)IgA(+) B cells could be a marker for treatment with TNF-α blockers. These findings of B cells as emerging key players provide a rationale for a systematic study on B-cell ablative therapy in patients with sarcoidosis.
Thyroid nodules in Iraq

Two groups of patients with solitary thyroid nodules have been analysed. One hundred patients of the first group under 20 years of age were managed conservatively with supplementary doses of thyroxin. Three hundred and thirty patients of the second group over the age of 20 were treated surgically. Seventeen percent of the first group had complete resolution of the thyroid nodule. The majority (eighty-three patients) needed exploration for a residual lesion. In the two groups, adenomatous goitre constituted the most frequent pathological finding. True adenoma was the next in frequency. Malignant nodules were found in ten cases (3.0%) of the second group; none was found in the first group. The overall incidence of carcinoma in solitary thyroid nodules in this study was 2·3%.
Effect of smoking on semen quality of infertile men in Shandong, China.

AIM To study the effect of smoking on the semen quality in infertile men in Shandong Province, China. METHODS Adult non-drinker males attending the infertility clinic, including 110 non-smokers and 191 smokers, were recruited for the study. Sixty-one fertile, non-smoker and non-drinker males, who had one or more children, served as the controls. The smokers were divided into subgroups according to the amount and duration of smoking. Semen parameters (semen volume and sperm density, viability, motility, and morphology) were examined and seminal plasma contents of Zn , Cu and superoxide dismutase (SOD) determined. RESULTS The semen volume and acidity, and the sperm density, viability and forward progression, as well as the seminal plasma contents of Zn, Cu and SOD were much lower in the medium, heavy and long-term smokers than in the non-smokers (P < 0.01). The sperm density, viability and forward progression, and the seminal plasma Zn, Cu and SOD levels were negatively correlated with the amount and duration of cigarette smoking (P < 0.01). CONCLUSION Medium, heavy and long-term smoking adversely affected the semen quality in a population of men visiting the infertility clinic in Shandong, China.
Definition of the Mycobacterial SOS Box and Use To Identify LexA-Regulated Genes in Mycobacterium tuberculosis

ABSTRACT The bases of the mycobacterial SOS box important for LexA binding were determined by replacing each base with every other and examining the effect on the induction of a reporter gene following DNA damage. This analysis revealed that the SOS box was longer than originally thought by 2 bp in each half of the palindromic site. A search of the Mycobacterium tuberculosis genome sequence with the new consensus, TCGAAC(N)4GTTCGA, identified 4 sites which were perfect matches and 12 sites with a single mismatch which were predicted to bind LexA. Genes which could potentially be regulated by these SOS boxes were ascertained from their positions relative to the sites. Examination of expression data for these genes following DNA damage identified 12 new genes which are most likely regulated by LexA as well as the known M. tuberculosis DNA damage-inducible genes recA, lexA, and ruvC. Of these 12 genes, only 2 have a predicted function: dnaE2, a component of DNA polymerase III, and linB, which is similar to 1,3,4,6-tetrachloro-1,4-cylcohexadiene hydrolase. Curiously, of the remaining 10 genes predicted to be LexA regulated, 7 are members of the M. tuberculosis 13E12 repeat family, which has some of the characteristics of mobile elements.
Expression of SPARC like protein 1 (SPARCL1), extracellular matrix-associated protein is down regulated in gastric adenocarcinoma.

BACKGROUND SPARC-like protein 1 (SPARCL1/Hevin), a member of the SPARC family is defined by the presence of a highly acidic domain-I, a follistatin-like domain, and an extracellular calcium (EC) binding domain. SPARCL1 has been shown to be down-regulated in many types of cancer and may serve as a negative regulator of cell growth and proliferation. METHODS Both tumor and adjacent normal tissue were collected from patients with gastric adenocarcinoma. Monoclonal antibody developed against recombinant SPARCL1 was used to analyze the expression of SPARCL1 by immunohisto chemical and western blotting (WB) analysis. RESULTS The expression of SPARCL1 was found to be significantly lower or negligible in gastric adenocarcinoma tissues in nearly all of the cases in comparison with adjacent normal tissue. This comparison was found to be independent of the patient's age, sex, and stage of cancer. CONCLUSIONS We postulate that down regulation of SPARCL1 may be related to inactivation of its tumor suppressor functions and might play an important role in the development of gastric adenocarcinoma.
Tissue-Specific Messenger Ribonucleic Acid Expression of 11β-Hydroxysteroid Dehydrogenase Types 1 and 2 and the Glucocorticoid Receptor within Rat Placenta Suggests Exquisite Local Control of Glucocorticoid Action.

Placental 11β-hydroxysteroid dehydrogenase (11β-HSD) regulates transplacental passage of maternal glucocorticoids to the fetus and is thus a key determinant of fetal glucocorticoid levels. It has also been proposed that placental 11β-HSD expression may influence local glucocorticoid actions by regulating access of corticosterone to the glucocorticoid receptor (GR) or mineralocorticoid receptor (MR). Therefore, the present study used a rat model to assess whether the GR or MR are coexpressed with the two forms of 11β-HSD (types 1 and 2) in the placental labyrinth zone, the major site of maternal-fetal transfer, and in the basal zone, the primary site of placental hormone synthesis. In situ hybridization analysis was used to assess messenger RNA (mRNA) expression for the GR, MR, 11β-HSD-1, and 11β-HSD-2 in the two placental zones on days 16, 19 and 22 of pregnancy (term = day 23). Whereas expression of the GR appeared relatively unchanged in both zones at these three stages of pregnancy, that of 11β-HSD-1 c.
Further observations on the serological response to experimental Salmonella typhimurium in chickens measured by ELISA

SUMMARY An indirect ELISA developed for the serological detection of Salmonella typhimurium in chickens using lipopolysaccharide as detecting antigen has been evaluated further in experimental infections. Following oral infection of 24-week-old laying hens with an invasive strain of S. typhimurium, high titres of specific circulating IgG were induced which were maintained for 20 weeks. Similar IgG titres were found in egg yolk. When 4-day-old chickens were infected high antibody titres persisted for 45 weeks. Chickens inoculated orally or intramuscularly with different numbers of S. typhimurium organisms showed graded serum IgG responses to LPS. The IgG titres in experimentally infected in-bred lines of chickens which showed greater genetic resistance to salmonella infection were significantly lower than those found in more susceptible lines. Oral and intramuscular infection with 18 different types of enterobacteria, including avian pathogenic E. coli, Citrobacter spp. , Klebsiella spp. , Proteus spp. and citrobacter-like organisms possessing some salmonella LPS (none possessed the 0–4 antigen) and flagella antigens, did not induce S. typhimurium LPS-specific IgG responses. Chickens infected orally with rough or non-flagellate mutants of S. typhimurium did not induce high titres of LPS or flagella-specific IgG respectively. Sera obtained from S. typhimurium-infected chickens showed much higher titres against S. typhimurium LPS than with those antigens from other serotypes, including S. enteritidis.