tbuckley/cabot-search huggingface dataset:
Exposure of Neonatal Rats to Parathion Elicits Sex-Selective Impairment of Acetylcholine Systems in Brain Regions during Adolescence and Adulthood
Authors: Theodore A. Slotkin, Bethany E. Bodwell, Ian T. Ryde, Edward D. Levin, Frederic J. Seidler
Journal: Environmental Health Perspectives (2008)

Organophosphates elicit developmental neurotoxicity through multiple mechanisms other than their shared property as cholinesterase inhibitors. Accordingly, these agents may differ in their effects on specific brain circuits.We gave parathion to neonatal rats [postnatal days (PNDs) 1-4], at daily doses of 0.1 or 0.2 mg/kg, spanning the threshold for barely detectable cholinesterase inhibition and systemic effects.We assessed neurochemical indices related to the function of acetylcholine (ACh) synapses (choline acetyltransferase, presynaptic high-affinity choline transporter, nicotinic cholinergic receptors) in brain regions comprising all the major ACh projections, with determinations carried out from adolescence to adulthood (PNDs 30, 60, and 100).Parathion exposure elicited lasting alterations in ACh markers in the frontal/parietal cortex, temporal/occipital cortex, midbrain, hippocampus, and striatum. In cerebrocortical areas, midbrain, and hippocampus, effects in males were generally greater than in females, whereas in the striatum, females were targeted preferentially. Superimposed on this general pattern, the cerebrocortical effects showed a nonmonotonic dose-response relationship, with regression of the defects at the higher parathion dose; this relationship has been seen also after comparable treatments with chlorpyrifos and diazinon and likely represents the involvement of cholinesterase-related actions that mask or offset the effects of lower doses.Neonatal exposure to parathion, at doses straddling the threshold for cholinesterase inhibition, compromises indices of ACh synaptic function in adolescence and adulthood. Differences between the effects of parathion compared with chlorpyrifos or diazinon and the non-monotonic dose-effect relationships reinforce the conclusion that various organophosphates diverge in their effects on neurodevelopment, unrelated to their anticholinesterase actions.
Response to high frequency jet ventilation may predict the need for extracorporeal membrane oxygenation
Authors: DL Stewart, TV Dela Cruz, SD Duncan, LN Cook
Journal: European Respiratory Journal (1996)

The aim of this study was to determine predictors of response whilst using high frequency jet ventilation (HFJV) for infants in intractable respiratory failure, in order to avoid the utilization of extracorporeal membrane oxygenation (ECMO). We reviewed patient demographics, ventilator parameters, blood gas values, length of oxygen therapy and use of surfactant and outcome, in infants given a 4 h trial of HFJV as the minimum to eliminate those infants where HFJV is used as a bridge to ECMO. The study was carried out in the neonatal intensive care nursery at Kosair Children's Hospital in Louisville, Kentucky, which provides high frequency ventilation and ECMO. Thirty infants who were eligible for ECMO and who met the study criteria were divided into two groups based upon response to HFJV. Twenty two infants responded to HFJV and eight nonresponders required ECMO after a trial of HFJV. Infants responding during HFJV demonstrated a significant decrease in oxygenation index without an escalation of mean airway pressure within 4 h after the initiation of HFJV. These infants had lower birth weights and an increased incidence of respiratory distress syndrome. No statistical differences were found in length of ventilation, days of oxygen therapy or duration of HFJV between the groups. Infants in intractable respiratory failure, who are eligible for extracorporeal membrane oxygenation, should receive a trial of high frequency jet ventilation, especially if the cause is respiratory distress syndrome unresponsive to surfactant therapy. During high frequency jet ventilation, the oxygenation index and mean airway pressure should be monitored serially, since they may predict the need for extracorporeal membrane oxygenation.
Correlation of CD4:CD8 ratio and tumour necrosis factor (TNF)alpha levels in induced sputum with bronchoalveolar lavage fluid in pulmonary sarcoidosis
Authors: Y. P Moodley
Journal: Thorax (2000)

<h3>BACKGROUND</h3> An increased CD4:CD8 lymphocyte ratio and raised cytokine levels in bronchoalveolar lavage (BAL) fluid are characteristic of pulmonary sarcoidosis. Sputum induction has been used as a non-invasive tool for investigating the airways and may be useful in investigating inflammation in patients with sarcoidosis in whom endobronchial, peribronchial, and parenchymal inflammation is present. This study aimed to correlate the total and differential cell counts, CD4:CD8 ratio, and tumour necrosis factor (TNF)α levels between induced sputum and BAL fluid in patients with pulmonary sarcoidosis. <h3>METHODS</h3> Fourteen patients with newly diagnosed biopsy proven sarcoidosis and six healthy controls were investigated. Sputum induction and BAL was carried out at the initial visit and repeated following six months of treatment with oral prednisone. <h3>RESULTS</h3> There was no correlation of differential cell counts between induced sputum and BAL fluid. The CD4:CD8 ratio in induced sputum correlated strongly with that in BAL fluid (5.5 (0.4:1) versus 4.4 (0.2:1);<i>r</i> = 0.8, p&lt;0.001) and the fall in the ratio following six months of treatment in sputum paralleled that in BAL fluid (3.4 (0.2:1) versus 2.4 (0.2:1)). The TNFα levels in sputum also correlated with levels in the BAL fluid (11.9 (1.5) pg/ml versus 17.6 (2.7) pg/ml; <i>r</i> = 0.8, p&lt;0.001). The fall in sputum TNFα levels following six months of treatment paralleled the fall in BAL fluid levels (6.7 (0.9) pg/ml versus 11.6 (1.3) pg/ml). <h3>CONCLUSIONS</h3> The CD4:CD8 ratio and TNFα levels in induced sputum correlated with those in BAL fluid and paralleled changes with treatment. Induced sputum may therefore be a non-invasive surrogate for certain parameters in BAL fluid in patients with sarcoidosis.
Fatty Acid Synthase Polymorphisms, Tumor Expression, Body Mass Index, Prostate Cancer Risk, and Survival
Authors: Paul L. Nguyen, Jing Ma, Jorge E. Chavarro, Matthew L. Freedman, Rosina Lis, Giuseppe Fedele, Christopher Fiore, Weiliang Qiu, Michelangelo Fiorentino, Stephen Finn, Kathryn L. Penney, Anna Eisenstein, Fredrick R. Schumacher, Lorelei A. Mucci, Meir J. Stampfer, Edward Giovannucci, Massimo Loda
Journal: Journal of Clinical Oncology (2010)

Fatty acid synthase (FASN) regulates de novo lipogenesis, body weight, and tumor growth. We examined whether common germline single nucleotide polymorphisms (SNPs) in the FASN gene affect prostate cancer (PCa) risk or PCa-specific mortality and whether these effects vary by body mass index (BMI).
Routine Blood Cultures From Febrile Outpatients
Authors: John M. Eisenberg
Journal: JAMA (1976)

Of 565 febrile patients examined in the emergency room of a metropolitan hospital, 210 had blood samples cultured (37.1%). Bacteremia was present in 9 of 86 patients who were admitted to the hospital but in only one of 124 patients who were not admitted (<i>P</i>&lt;.005). Thus, approximately 5% of febrile adult outpatients had bacteremia, and these patients were usually admitted before the results of the culture were known. Since positive cultures were found so infrequently in patients not admitted and were, therefore, of little value in guiding the treatment of these patients, we conclude that use of routine blood cultures to screen for bacteremia is unnecessary for febrile adult outpatients who are not admitted to the hospital. (<i>JAMA</i>236:2863-2865, 1976)
The Effect of Hexamethonium upon Cerebral Blood Flow and Metabolism in Patients with Premalignant and Malignant Hypertension
Authors: CHARLES W. CRUMPTON, GEORGE G. ROWE, ROBERT C. CAPPS, JANET J. WHITMORE, QUILL R. MURPHY
Journal: Circulation (1955)

In 13 patients with grade III or grade IV hypertensive retinopathy the effect of intramuscular hexamethonium bromide on cerebral circulation and metabolism has been studied. The results have been compared with Dewar's study of hexamethonium in less severe hypertensive patients and with Kety's results following differential spinal sympathetic block. Sixty minutes after intramuscular hexamethonium, mean arterial blood pressure fell 39 per cent, cerebral vascular resistance was reduced 29 per cent, and cerebral blood flow decreased 16 per cent. Cerebral oxygen consumption was maintained at the expense of a reduction in cerebral venous oxygen saturation.
The Social Ecology of Child Health and Well-Being
Authors: Felton Earls, Mary Carlson
Journal: Annual Review of Public Health (2001)

The term social ecology refers to the nested arrangement of family, school, neighborhood, and community contexts in which children grow up. In this chapter, new directions in public health science as reflected in the theoretical and methodological implications of the concept are explored. The contributions of this ecologically oriented approach to child health practice, designed as it is from a health promotions perspective, are considered. A critique of the term social capital is also presented because of its growing popularity in matters of child health. The point is made that application of this vague term carries the serious risk of misspecifying social phenomena. Future trends in the promotion of child well-being are in a position to flourish given the confluence of advances in theory, methods, and analytical capacity. The capacity to benefit children is also enhanced as public health science aims to translate the principles of child rights into health practice and policy.
The devastating power of platelets in COPD exacerbations: can aspirin save lives in COPD?
Authors: Don D Sin
Journal: Thorax (2014)

The human and societal burden of COPD is alarming. Despite large reductions in smoking rates across industrialised nations, COPD mortality has increased by 60% over the past 20 years, making it the second leading cause of morbidity and mortality in the USA and elsewhere.1 Most of the COPD-related deaths occur during or shortly following acute exacerbations (or ‘lung attacks’). Unfortunately, severe lung attacks are common, with one in six patients requiring hospitalisation for urgent care each year.2 Despite best therapy, 1 in 12 of these patients will succumb to their disease in hospital.3 Even those who survive will experience persistent morbidity from their recent lung attack and never regain their lost health status. Furthermore, one in three patients will have another lung attack in 6–12 months.3 Regrettably, acute and chronic treatments for COPD are suboptimal. Despite global drug expenditures that exceed $36 billion annually for COPD care,4 none of the currently available drugs reduces mortality or modifies disease progression as defined by …
Hiccups as an Adverse Reaction to Cancer Chemotherapy
Authors: Y. Takiguchi
Journal: JNCI Journal of the National Cancer Institute (2002)

Although most research reports on cancer chemotherapy have shown no data on the occurrence of hiccups as an adverse reaction, several reports (1–3) have disclosed a high incidence of hiccups, i.e., in more than 30% of treated patients during chemotherapy. Because most cancer chemotherapy regimens consist of multiple drugs, including cytotoxic agents, 5-hydroxytryptamine 3 (5-HT3) receptor antagonists, and corticosteroids, identifying the causative drug is very difficult. Of those drugs, dexamethasone, which is used for the prophylaxis of delayed emesis, has already been shown to cause hiccups (4), although other drugs, including chemotherapeutic agents, cannot be ruled out. To determine the frequency of hiccups associated with the use of specific
Comparative Transcriptome Analyses Reveal Core Parasitism Genes and Suggest Gene Duplication and Repurposing as Sources of Structural Novelty
Authors: Zhenzhen Yang, Eric K. Wafula, Loren A. Honaas, Huiting Zhang, Malay Das, Monica Fernandez-Aparicio, Kan Huang, Pradeepa C.G. Bandaranayake, Biao Wu, Joshua P. Der, Christopher R. Clarke, Paula E. Ralph, Lena Landherr, Naomi S. Altman, Michael P. Timko, John I. Yoder, James H. Westwood, Claude W. dePamphilis
Journal: Molecular Biology and Evolution (2014)

The origin of novel traits is recognized as an important process underlying many major evolutionary radiations. We studied the genetic basis for the evolution of haustoria, the novel feeding organs of parasitic flowering plants, using comparative transcriptome sequencing in three species of Orobanchaceae. Around 180 genes are upregulated during haustorial development following host attachment in at least two species, and these are enriched in proteases, cell wall modifying enzymes, and extracellular secretion proteins. Additionally, about 100 shared genes are upregulated in response to haustorium inducing factors prior to host attachment. Collectively, we refer to these newly identified genes as putative "parasitism genes." Most of these parasitism genes are derived from gene duplications in a common ancestor of Orobanchaceae and Mimulus guttatus, a related nonparasitic plant. Additionally, the signature of relaxed purifying selection and/or adaptive evolution at specific sites was detected in many haustorial genes, and may play an important role in parasite evolution. Comparative analysis of gene expression patterns in parasitic and nonparasitic angiosperms suggests that parasitism genes are derived primarily from root and floral tissues, but with some genes co-opted from other tissues. Gene duplication, often taking place in a nonparasitic ancestor of Orobanchaceae, followed by regulatory neofunctionalization, was an important process in the origin of parasitic haustoria.
Ischaemic colitis and abdomino-perineal excision of the rectum
Authors: M. L. Thomas, J. M. Wellwood
Journal: Gut (1973)

Two patients are presented in whom ischaemic colitis followed some years after abdomino-perineal excision of the rectum for carcinoma. The first patient was a young man without evidence of arterial disease and the second patient suffered from auricular fibrillation, thought to be due to ischaemic heart disease. Ligation of the inferior mesenteric artery in the operation of abdomino-perineal excision of the rectum may reduce the blood flow through the marginal artery of Drummond rendering the remaining colon more liable to ischaemic damage. Patients who pass bright blood through a colostomy following abdomino-perineal excision of the rectum for carcinoma may have ischaemic colitis rather than a recurrence of the neoplasm.
Prospective Study of <i>FGFR3</i> Mutations As a Prognostic Factor in Nonmuscle Invasive Urothelial Bladder Carcinomas
Authors: Silvia Hernández, Elena López-Knowles, Josep Lloreta, Manolis Kogevinas, Alex Amorós, Adonina Tardón, Alfredo Carrato, Consol Serra, Núria Malats, Francisco X. Real
Journal: Journal of Clinical Oncology (2006)

Purpose To determine the frequency and the prognostic value of fibroblast growth factor receptor 3 (FGFR3) mutations in patients with nonmuscle invasive bladder tumors according to tumor stage and grade. Patients and Methods Seven hundred seventy-two patients with newly diagnosed bladder tumors were recruited. Tumors were reviewed by expert pathologists. Patients were prospectively followed-up (median, 62.6 months for disease-free patients) through review of hospital records and telephone interviews. The sequence of exons 7 and 10 of FGFR3 was analyzed by polymerase chain reaction and direct sequencing. We assessed the association of mutations with stage and grade. The predictive value of mutations for recurrence, progression, and mortality were assessed using Kaplan-Meier and Cox multivariable models. Results Mutations were more common among low malignant potential neoplasms (LMPN; 77%) and TaG1/TaG2 tumors (61%/58%) than among TaG3 tumors (34%) and T1G3 tumors (17%). The S249C, Y375C, S248C, and G372C mutations accounted for 91.5% of all sequence changes. The A393E substitution was associated with LMPN (P &lt; .001). The F386L polymorphism was more frequent among patients with low-grade tumors (odds ratio, 6.97; 95%CI, 1.40 to 47.06; P = .009). In the multivariable analysis of all superficial tumors, mutations were associated with increased risk of recurrence. However, in the stratified analyses only patients with TaG1 tumors had a significantly higher risk of recurrence (hazard ratio, 2.12; 95%CI, 1.28 to 3.53; P = .004). Conclusion The findings of this large study strongly support the notion that FGFR3 mutations characterize a subgroup of bladder cancers with good prognosis; patients with mutant TaG1 tumors have a higher risk of recurrence; and the F386L variant is selectively associated with low-grade tumors.
Systemic antineutrophil cytoplasmic antibody vasculitis associated with lymphoid neoplasia
Authors: M A Hamidou
Journal: Annals of the Rheumatic Diseases (2001)

Two cases of systemic antineutrophil cytoplasmic antibody (ANCA) vasculitis in the setting of chronic lymphocytic leukaemia and angioimmunoblastic lymphadenopathy type T cell lymphoma are reported. The two patients had fever of unknown origin associated with cutaneous vasculitis and "pulmonary-renal syndrome" with alveolar haemorrhage. Despite anti-infectious treatments, steroids, and chemotherapy, the vasculitis had a fatal paraneoplastic course in several weeks. When infection is excluded in patients with malignancy, atypical features should be promptly investigated for systemic vasculitis, and an ANCA test performed.
TLR4 Facilitates Translocation of Bacteria across Renal Collecting Duct Cells
Authors: Cécilia Chassin, Sophie Vimont, Franc[COMBINING CEDILLA]oise Cluzeaud, Marcelle Bens, Jean-Michel Goujon, Béatrice Fernandez, Alexandre Hertig, Eric Rondeau, Guillaume Arlet, Mathias W. Hornef, Alain Vandewalle
Journal: Journal of the American Society of Nephrology (2008)

Uropathogenic Escherichia coli (UPEC) are the most frequent causes of urinary tract infections and pyelonephritis. Renal medullary collecting duct (MCD) cells are the intrarenal site to which UPEC strains prefer to adhere and initiate an inflammatory response, but the ability of UPEC strains to translocate across impermeant MCD cells has not been demonstrated definitively. Here, several UPEC strains adhered to the apical surface and translocated across confluent murine inner MCD cells grown on filters. UPEC strains expressing cytolytic and vacuolating cytotoxins disrupted the integrity of cell layers, whereas noncytolytic UPEC strains passed through the cell layers without altering tight junctions. Apical-to-basal transcellular translocation was dramatically reduced after extinction of Toll-like receptor 4 (TLR4) and the lipid raft marker caveolin-1 by small interfering RNA. Furthermore, disruption of lipid raft integrity by filipin III and methyl-beta-cyclodextrin significantly reduced both the transcellular translocation of UPEC across murine inner MCD cell layers and the stimulation of proinflammatory mediators. Bacterial translocation was also significantly reduced in primary cultures of TLR4-deficient mouse MCD cells compared with MCD cells from wild-type mice. Benzyl alcohol, an anesthetic that enhances membrane fluidity, favored the recruitment of caveolin-1 in lipid rafts and increased the translocation of UPEC across cultured TLR4-deficient MCD cells. These findings demonstrate that the transcellular translocation of UPEC strains across impermeant layers of MCD cells may occur through lipid rafts via a TLR4-facilitated process.
Is the oocyte a non-professional phagocyte?
Authors: R Bronson
Journal: Human Reproduction Update (1998)

Although fertilization has been described as a series of events during which the spermatozoon penetrates the oocyte, introducing its nuclear contents, there is strong evidence that either gamete can be the active partner at different stages of this process. Indeed, while sperm motility is essential for its penetration of the egg vestments immotile spermatozoa are capable of entering the ooplasm once they adhere to the oolemma. Entry of the spermatozoa into the oocyte appears to require two distinct but perhaps related events, namely gamete cell membrane fusion, at the level of the equatorial segment of the sperm acrosome with the oolemma, and a quasi-phagocytic event involving the incorporation by the oocyte of the rostral portion of the acrosome-reacted spermatozoon head within an oolemmal-derived vesicle. This review explores the biology of phagocytosis by macrophages and non-professional phagocytes, and in particular the roles played by phagocytosis-promoting receptors (FcgR, complement receptors and integrins), in both signal transduction and their linkage with the cytoskeleton. It asks whether the oocyte might not utilize similar mechanisms during its incorporation of the spermatozoon.
Hematopoietic Stem-Cell Transplantation for Acute Leukemia in Relapse or Primary Induction Failure
Authors: Michel Duval, John P. Klein, Wensheng He, Jean-Yves Cahn, Mitchell Cairo, Bruce M. Camitta, Rammurti Kamble, Edward Copelan, Marcos de Lima, Vikas Gupta, Armand Keating, Hillard M. Lazarus, Mark R. Litzow, David I. Marks, Richard T. Maziarz, David A. Rizzieri, Gary Schiller, Kirk R. Schultz, Martin S. Tallman, Daniel Weisdorf
Journal: Journal of Clinical Oncology (2010)

Purpose Patients with acute leukemia refractory to induction or reinduction chemotherapy have poor prognoses if they do not undergo hematopoietic stem-cell transplantation (HSCT). However, HSCT when a patient is not in complete remission (CR) is of uncertain benefit. We hypothesized that pretransplantation variables may define subgroups that have a better prognosis. Patients and Methods Overall, 2,255 patients who underwent transplantation for acute leukemia in relapse or with primary induction failure after myeloablative conditioning regimen between 1995 and 2004 were reported to the Center for International Blood and Marrow Transplant Research. The median follow-up of survivors was 61 months. We performed multivariate analysis of pretransplantation variables and developed a predictive scoring system for survival. Results The 3-year overall survival (OS) rates were 19% for acute myeloid leukemia (AML) and 16% for acute lymphoblastic leukemia (ALL). For AML, five adverse pretransplantation variables significantly influenced survival: first CR duration less than 6 months, circulating blasts, donor other than HLA-identical sibling, Karnofsky or Lansky score less than 90, and poor-risk cytogenetics. For ALL, survival was worse with the following: first refractory or second or greater relapse, ≥ 25% marrow blasts, cytomegalovirus-seropositive donor, and age of 10 years or older. Patients with AML who had a predictive score of 0 had 42% OS at 3 years, whereas OS was 6% for a score ≥ 3. Patients with ALL who had a score of 0 or 1 had 46% 3-year OS but only 10% OS rate for a score ≥ 3. Conclusion Pretransplantation variables delineate subgroups with different outcomes. HSCT during relapse can achieve long-term survival in selected patients with acute leukemia.