tbuckley/cabot-search huggingface dataset:
Thiopurines prevent advanced colorectal neoplasia in patients with inflammatory bowel disease
Authors: Fiona D M van Schaik, Martijn G H van Oijen, Hugo M Smeets, Geert J M G van der Heijden, Peter D Siersema, Bas Oldenburg
Journal: Gut (2011)

Calretinin (CR)-expressing periglomerular (PG) cells are the most abundant interneurons in the glomerular layer of the olfactory bulb. They are predominately generated postnatally from the septal and dorsal subventricular zones that continue producing them well into adulthood. Yet, little is known about their properties and functions. Using transgenic approaches and patch-clamp recording in mice of both sexes we show that CR(+) PG cells of both septal and dorsal origin have homogeneous morphological and electrophysiological properties. However, unlike other PG cells, these axonless neurons express a surprisingly small repertoire of voltage-activated channels and do not fire or fire at most a single and often small action potential. Moreover, they are not innervated by olfactory sensory neurons and receive little synaptic inputs from mitral or tufted cells at excitatory synapses where NMDA receptors predominate. These membrane and synaptic properties, that resemble those of newborn immature neurons not yet integrated in the network, persist over time and limit the recruitment of CR(+) PG cells by afferent inputs that strongly drive local network activity. Together, our results show that postnatally generated CR(+) PG cells continuously supply a large pool of neurons with unconventional properties. These data also question the contribution of CR(+) PG cells in olfactory bulb computation. <b>SIGNIFICANCE STATEMENT</b> Calretinin-expressing PG cells are by far the most abundant interneurons in the glomerular layer of the olfactory bulb. They are continuously produced during postnatal life, including adulthood, from neural stem cells located in the subventricular zones. Surprisingly, unlike other postnatally generated newborn neurons that quickly integrate into preexisting olfactory bulb networks, calretinin-expressing PG cells retain immature properties that limit their recruitment in local network activity for weeks, if not months, as if they would never fully mature. The function of this so far unsuspected pool of latent neurons is still unknown.
Cardiogenic Shock in Patients With Acute Ischemic Syndromes With and Without ST-Segment Elevation
Authors: David R. Holmes, Peter B. Berger, Judith S. Hochman, Christopher B. Granger, Trevor D. Thompson, Robert M. Califf, Alec Vahanian, Eric R. Bates, Eric J. Topol
Journal: Circulation (1999)

Background —Cardiogenic shock is usually considered a sequela of ST-segment elevation myocardial infarction. There are limited prospective data on the incidence and significance of shock in non−ST-segment elevation patients. This study assessed the incidence and outcomes of cardiogenic shock developing after enrollment among patients with and without ST-segment elevation in the Global Use of Strategies To Open Occluded Coronary Arteries (GUSTO)-IIb trial. Methods and Results —Among 12 084 patients in GUSTO-IIb who did not present with cardiogenic shock, 4092 (34%) had and 7991 (66%) did not have ST-segment elevation on the enrollment ECG. Cardiogenic shock developed in 4.2% of ST-segment elevation patients compared with 2.5% of patients without ST-segment elevation (odds ratio, 0.581; 95% CI, 0.472 to 0.715; P &lt;0.001). Shock developed significantly later among patients without ST-segment elevation. There were significant differences in baseline characteristics between shock patients with and without ST-segment elevation: Patients without ST-segment elevation were older, more frequently had diabetes mellitus and 3-vessel disease, but had less TIMI grade 0 flow at angiography. Regardless of the initial ECG, mortality was high: 63% among patients with ST-segment elevation and 73% in those without ST-segment elevation. Conclusions —Cardiogenic shock occurs in the setting of acute ischemic syndromes regardless of whether ST-segment elevation is present. The incidence, patient characteristics, timing, clinical course, and angiographic findings differ between the 2 groups. Mortality from cardiogenic shock is similarly high among patients with and without ST-segment elevation.
Assessment of needs, health-related quality of life, and satisfaction with care in breast cancer patients to better target supportive care
Authors: A. Brédart, J.-L. Kop, A.-C. Griesser, C. Fiszer, K. Zaman, B. Panes-Ruedin, W. Jeanneret, J.-F. Delaloye, S. Zimmers, V. Berthet, S. Dolbeault
Journal: Annals of Oncology (2013)
Human marrow erythropoiesis in culture: II. Heterogeneity in the morphology, time course of colony formation, and sedimentation velocities of the colony‐forming cells
Authors: Makio Ogawa, Martha D. Maceachern, Lobelia Avila
Journal: American Journal of Hematology (1977)

Abstract Time course examination on human marrow erythxoid colony formation was carried out in methylcellulose culture by scoring colonies with clear signs of hemoglobinization. The colonies were arbitrarily divided into 3 categories: small colony, containing fewer than 50 cells; medium‐sized colony, containing 50‐500 cells; and large colony, containing more than 500 cells. The majority of the large colonies assumed the morphology of bursts consisting of several subcolonies. Small colonies became hemoglobinized, reached their peak on Day 4, and rapidly disappeared. Medium‐sized colonies gradually increased, reached their peak on Day 8, and then slowly declined. Large colonies became hemoglobinized beginning on Day 11 and continued to be present until Day 18. We then examined the cell sizes of the erythropoietic precursor using sedimentation velocity analysis. Bone marrow nucleated cells were separated in a Staput apparatus and fractions of equal volume were analyzed for their content of colony‐forming units (CFU). The mean of modal sedimentation velocities of late erythroid precursors, CFU‐E 4 (CFU‐E for 4‐day‐old small colonies), was 6.46 mm/hour, while that of CFU‐E 14 (CFU‐E for 14‐day‐old large colonies) was 5.17 mm/hour. These studies demonstrate the heterogeneity of human erythroid precursors assayable in culture and emphasize the necessity for clear standardization of scoring colonies.
The <i>GNAS1</i> T393C Polymorphism Predicts Survival in Patients with Clear Cell Renal Cell Carcinoma
Authors: Ulrich H. Frey, Gerd Lümmen, Tobias Jäger, Karl-Heinz Jöckel, Kurt W. Schmid, Herbert Rübben, Norbert Müller, Winfried Siffert, Andreas Eisenhardt
Journal: Clinical Cancer Research (2006)

G proteins mediate signaling from cell surface receptors to specific intracellular proteins. In vitro cancer cell line studies revealed a link between the Galphas protein and proapoptotic processes. We have recently shown that TT genotypes of the GNAS1 T393C polymorphism display increased transcription of Galphas and a more favorable clinical course in bladder and colorectal cancer patients compared both with TC or CC genotypes.In the present study, 150 patients with clear cell renal cell carcinoma surgically treated by nephrectomy with curative intent were retrospectively genotyped to elucidate a potential association between T393C genotypes and clinical outcome.The C-allele frequency in the renal cell carcinoma patient group was 0.51, which is not significantly different from that of a healthy blood donor group. Kaplan-Meier curves for tumor progression, development of metastasis, and tumor-related death showed a significant association of the T393C polymorphism with outcome (5-year cancer-specific survival rates: TT, 91%; TC, 81%; CC, 69%; P = 0.015). Multivariate Cox proportional analysis of a 10-year follow-up confirmed the T393C polymorphism as an independent prognostic factor in clear cell renal cell carcinoma. Homozygous CC patients were at highest risk for progression (hazard ratio, 2.48; P = 0.009) or tumor-related death (hazard ratio, 3.15; P = 0.018) compared with T-allele carriers.Our results show that besides tumor stage, lymph node status, and tumor grade, the GNAS1 T393C status is a novel independent host factor for disease progression in patients with clear cell renal cell carcinoma and provides further evidence for the T393C polymorphism as a general prognostic tumor marker.
Efficacy, Safety, and Potential Biomarkers of Sunitinib Monotherapy in Advanced Hepatocellular Carcinoma: A Phase II Study
Authors: Andrew X. Zhu, Dushyant V. Sahani, Dan G. Duda, Emmanuelle di Tomaso, Marek Ancukiewicz, Onofrio A. Catalano, Vivek Sindhwani, Lawrence S. Blaszkowsky, Sam S. Yoon, Johanna Lahdenranta, Pankaj Bhargava, Jeffrey Meyerhardt, Jeffrey W. Clark, Eunice L. Kwak, Aram F. Hezel, Rebecca Miksad, Thomas A. Abrams, Peter C. Enzinger, Charles S. Fuchs, David P. Ryan, Rakesh K. Jain
Journal: Journal of Clinical Oncology (2009)

To assess the safety and efficacy of sunitinib in patients with advanced hepatocellular carcinoma (HCC) and explore biomarkers for sunitinib response.We conducted a multidisciplinary phase II study of sunitinib, an antivascular endothelial growth factor receptor tyrosine kinase inhibitor, in advanced HCC. Patients received sunitinib 37.5 mg/d for 4 weeks followed by 2 weeks of rest per cycle. The primary end point was progression-free survival (PFS). We used functional magnetic resonance imaging to evaluate vascular changes in HCC after sunitinib treatment. Circulating molecular and cellular biomarkers were evaluated before and at six time points after sunitinib treatment.Thirty-four patients were enrolled. The objective response rate was 2.9%, and 50% of patients had stable disease. Median PFS was 3.9 months (95% CI, 2.6 to 6.9 months), and overall survival was 9.8 months (95% CI, 7.4 months to not available). Grade 3 or 4 toxicities included leukopenia/neutropenia, thrombocytopenia, elevation of aminotransferases, and fatigue. Sunitinib rapidly decreased vessel leakiness, and this effect was more pronounced in patients with delayed progression. When evaluated early (at baseline and day 14) as well as over three cycles of treatment, higher levels of inflammatory molecules (eg, interleukin-6, stromal-derived factor 1alpha, soluble c-KIT) and circulating progenitor cells were associated with a poor outcome.Sunitinib shows evidence of modest antitumor activity in advanced HCC with manageable adverse effects. Rapid changes in tumor vascular permeability and circulating inflammatory biomarkers are potential determinants of response and resistance to sunitinib in HCC. Our study suggests that control of inflammation might be critical for improving treatment outcome in advanced HCC.
Genetic Disease in the Children of Danish Survivors of Childhood and Adolescent Cancer
Authors: Jeanette F. Winther, Jørgen H. Olsen, Huiyun Wu, Yu Shyr, John J. Mulvihill, Marilyn Stovall, Annelise Nielsen, Marianne Schmiegelow, John D. Boice
Journal: Journal of Clinical Oncology (2011)

Purpose Preconception radiation and chemotherapy have the potential to produce germ cell mutations leading to genetic disease in the next generation. Dose-response relationships were evaluated between cancer treatments and untoward pregnancy outcomes. Patients and Methods A case-cohort study was conducted involving 472 Danish survivors of childhood and adolescent cancer and their 1,037 pregnancies. Adverse outcomes included 159 congenital malformations, six chromosomal abnormalities, seven stillbirths, and nine neonatal deaths. Preconception radiation doses to the gonads, uterus, and pituitary gland and administered chemotherapy were quantified based on medical records and related to adverse outcomes using a generalized estimating equation model. Results No statistically significant associations were found between genetic disease in children and parental treatment with alkylating drugs or preconception radiation doses to the testes in male and ovaries in female cancer survivors. Specifically, the risk of genetic disease was similar among the children of irradiated survivors when compared with nonirradiated survivors (relative risk [RR], 1.02; 95% CI, 0.59 to 1.44; P = .94). A statistically significant association between abdomino-pelvic irradiation and malformations, stillbirths, and neonatal deaths was not seen in the children of female survivors overall (P = .07) or in the children of mothers receiving high uterine doses (mean, 13.5 Gy; max, 100 Gy; RR, 2.3; 95% CI, 0.95 to 5.56). Conclusion Mutagenic chemotherapy and radiotherapy doses to the gonads were not associated with genetic defects in children of cancer survivors. However, larger studies need to be conducted to further explore potential associations between high-dose pelvic irradiation and specific adverse pregnancy outcomes.
Aspergillosis in immunocompromised paediatric patients: associations with building hygiene, design, and indoor air.
Authors: K Anderson, G Morris, H Kennedy, J Croall, J Michie, M D Richardson, B Gibson
Journal: Thorax (1996)

Nosocomial aspergillosis is a well known complication of immunosuppression in cancer patients and those undergoing transplantation and has usually been associated with major building construction or demolition. An observational study is reported of the hospital environment associated with an outbreak of aspergillosis in a paediatric oncology ward.All cases of aspergillosis were identified from the hospital records and categorised as definite or probable according to the extent of supportive clinical and laboratory findings. All relevant aspects of building ventilation, air filtration, and aerosol generation considered relevant were examined and air samples for fungi were taken in triplicate at 25 sites using a slit sampler with appropriate culture media.Six cases of aspergillosis were identified over one year out of the 148 patients who attended the unit - the only part of the hospital where cases were found. Examination of the building services and function suggested that the cause or source was isolated to this paediatric oncology/haematology ward and may have been attributed to a defective disposal conduit door as well as the dispersal of a contaminated aerosol from the ward vacuum cleaner which had the highest measured concentrations of Aspergillus fumigatus in or around the building (65 colony forming units (cfu)/m3 compared with 0-6 cfu/m3 elsewhere). No further cases were identified in the two years after these hygiene arrangements were changed.The investigation of this outbreak of nosocomial aspergillosis identified several possible sources of fungally contaminated aerosol which could have been implicated as the cause. Their modification was followed by a reduction in the incidence of further cases. Each should be incorporated as an issue of importance in hospital building design and hygiene.
Does Living on a Farm during Childhood Protect against Asthma, Allergic Rhinitis, and Atopy in Adulthood?
Authors: BÉNÉDICTE LEYNAERT, CATHERINE NEUKIRCH, DEBORAH JARVIS, SUSAN CHINN, PETER BURNEY, FRANÇOISE NEUKIRCH
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

Recent studies of children suggest that factors encountered in a farm environment might protect against the development of allergy. However, it remains uncertain whether living on a farm in childhood is associated with a decreased risk of atopic diseases in adulthood. We analyzed data from 6,251 randomly selected adults 20 to 44 yr of age participating in the European Community Respiratory Health Survey (ECRHS). Subjects answered a detailed questionnaire and underwent specific IgE measurements to five allergens. After adjustment for potential confounders, including pet exposure in childhood, number of siblings, severe respiratory infection in childhood, and parental history of allergy, living on a farm in childhood was associated with a reduced risk of atopic sensitization in adulthood (OR = 0.76, CI 95% = 0.60–0.97). Compared with other adults, those who had lived on a farm as a child were less frequently sensitized to cat (OR = 0.63, CI 95% = 0.41–0.96) and to Timothy grass (OR = 0.68, CI 95% = 0.50–0.94), and were at lower risk of having nasal symptoms in the presence of pollen (OR = 0.80, CI 95% = 0.64–1.02). The protective effect of farming environment in childhood observed in this population-based sample of young adults provides evidence in favor of the hypothesis that environmental factors encountered in childhood may have a lifelong protective effect against the development of allergy.
L-palmitylcarnitine and calcium ions act similarly on excitatory ionic currents in avian ventricular muscle.
Authors: D Inoue, A J Pappano
Journal: Circulation Research (1983)

Palmitylcarnitine, an amphiphile that accumulates in and leaks from ischemic heart tissue, affected the fast sodium ion channel and the slow calcium channel in avian ventricular muscle. In the presence of 5.4 mM external potassium ion, palmitylcarnitine reduced the maximum rate of rise of the action potential and increased action potential duration at the plateau level without changing the resting potential. Steady state inactivation of the maximum rate of rise, an index of fast sodium ion current, was shifted by 3-6 mV to more positive potentials by palmitylcarnitine. Elevation of external calcium ion to 5.4 mM (normal = 1.8 mM), like palmitylcarnitine, reduced the maximum rate of rise and shifted the voltage at which the action potential was half maximum by 3 mV to more positive potentials without changing the resting potential. Elevated external calcium ion, unlike palmitylcarnitine, reduced the duration of action potentials initiated from a resting potential of -80 mV. Palmitylcarnitine and elevated external calcium ion increased the amplitude, the maximum rate of rise, and duration of calcium ion dependent action potentials recorded in the presence of 25 mM [K+]0 that completely inactivated the fast sodium ion channel. Steady state inactivation of the maximum rate of rise of calcium-dependent action potentials was consistently shifted to more positive potentials by palmitylcarnitine (3 mV) and by elevated external calcium ion (6 mV) when the initial external calcium ion was 0.9 mM. Palmitylcarnitine, like elevated calcium, evoked a positive inotropic effect in the presence of propranolol. The similarity of the effects of palmitylcarnitine (3 X 10(-5) to 3 X 10(-4)M) with those of elevated external calcium is consistent with the hypothesis that palmitylcarnitine, like elevated external calcium, influences sodium and calcium channel operation by an effect on membrane surface charge.
Antigen-Induced Murine B-Cell Lymphomas. III. Passive Anti-idiotype Serum Therapy and Its Combined Effect With Chemotherapy<xref ref-type="fn" rid="FN2">2</xref>
Authors: L L Lanier, G F Babcock, M A Lynes, G Haughton
Journal: JNCI Journal of the National Cancer Institute (1979)

The effectiveness of passive heterologous anti-idiotype (A-Id) serum therapy in combination with chemotherapy was investigated in the CH1 murine B-cell lymphoma system. Groups of B10-H-2aH-4bp/Wts mice were given small single doses (5–200 μl) of A-Id serum 2 days after a lethal tumor challenge of 102–103 CH1 cells. Most of these mice survived tumor-free for more than 80 days, whereas all control mice died within 33 days. If treatment was delayed until day 4, all mice succumbed to tumor, but some survived significantly longer than controls. Surprisingly, mice treated with a single large dose (0.5 ml) or multiple doses of A-Id serum all died of tumor as rapidly as untreated controls. A-Id-treated mice surviving the initial tumor were rechallenged with another lethal CH1 tumor inoculum. Ten of 20 rechallenged mice survived. Tumor-bearing mice were also treated with cyclophosphamide (Cy) to determine whether this agent could inhibit tumor growth. All mice given Cy (25–100 mg/kg) 4 days after they were given 2.5–10×102 CH1 cells survived indefinitely. If treatment was delayed until day 12, most mice died of tumor. However, Cy treatment increased the host survival time significantly. In contrast to the results with A-Id serum therapy, mice surviving after chemotherapy did not resist a second tumor challenge. In a subsequent experiment, A-Id serum therapy was combined with Cy drug treatment. Only 4 of 10 mice given 50 mg/kg Cy on day 11 after they received a 2.5×102 CH1 tumor challenge survived, and none of the untreated mice (0/5) or mice given A-Id serum only (0/4) on day 16 survived. By contrast, all 10 mice given 50 mg/kg Cy on day 11 and then 200 μl A-Id serum on day 16 survived throughout the observation period (>90 days).
Severe acute respiratory syndrome (SARS): epidemiology, diagnosis and management
Authors: G W K Wong
Journal: Thorax (2003)

<h3>Introduction</h3> Sodium glucose co-transporter 2 (SGLT2) inhibitors have been reported to benefit liver functions in patients with type 2 diabetes (T2D) with non-alcoholic fatty liver disease (NAFLD). The aim of this study is to critically appraise existing systematic reviews in order to consolidate evidence associating the use of SGLT2 inhibitors with beneficial hepatic results for patients with T2D with NAFLD. <h3>Methods</h3> This umbrella review searched relevant published systematic reviews of clinical trials from PubMed and Embase between inception and September 16, 2020. Two independent investigators appraised study quality using AMSTAR2 (Assessment of Multiple Systematic Reviews 2). The hepatic effects from SGLT2 inhibitors were summarized based on liver enzymes, liver fat, liver histology, liver cirrhosis and liver cancer. <h3>Results</h3> Of 25 screened potential systematic reviews, we ultimately included 7 in this study. However, none of them could be rated as being of high methodological quality. Five systematic reviews indicated that SGLT2 inhibitors could effectively decrease liver fat and liver parameters of alanine aminotransferase and gamma-glutamyl transferase in patients with NAFLD. Two systematic reviews indicated that SGLT2 inhibitors could reduce hepatosteatosis, as supported by biopsy-proven evidence of improvement from a small clinical trial, but no evidence of liver fibrosis improvement was found. <h3>Conclusions</h3> There is some association between SGLT2 inhibitor use and observed benefits to liver functions in patients with T2D with NAFLD, although the quality of current systematic reviews remains relatively low. Further evaluation of long-term liver outcomes with SGLT2 inhibitors in cases of liver cirrhosis and liver cancer is warranted.
α-Melanocyte Stimulating Hormone in the Modulation of Host Reactions*
Authors: ANNA CATANIA, JAMES M. LIPTON
Journal: Endocrine Reviews (1993)

α-MELANOCYTE-stimulating hormone (αMSH), a basic tridecapeptide, is derived from the precursor molecule POMC(l). The amino acid sequence of αMSH is identical to the 1–13 (N-terminal) amino acid sequence of ACTH although αMSH has little direct influence on glucocorticoid release from the adrenal gland. αMSH is found mainly in the pituitary, but it also occurs in lower concentrations in the central nervous system (CNS), the skin, and other sites (1). This peptide was named for its effect on pigmentation in amphibian skin, although its distribution in tissues of higher organisms suggests that it is important to other functions. Phylogenetically, αMSH is an “ancient” molecule, little changed over the last few hundred million years, and there is remarkable conservation of its amino acid sequence across species. Evidence that this endogenous neuropeptide is important to limitation of fever and inflammation in mammals, including man, suggests that αMSH has retained a role as a modulator of host responses (2–7).
Serum vitamin D levels and severe asthma exacerbations in the Childhood Asthma Management Program study
Authors: John M. Brehm, Brooke Schuemann, Anne L. Fuhlbrigge, Bruce W. Hollis, Robert C. Strunk, Robert S. Zeiger, Scott T. Weiss, Augusto A. Litonjua
Journal: Journal of Allergy and Clinical Immunology (2010)