tbuckley/cabot-search huggingface dataset:
Calcium exchange and ionized cytoplasmic calcium in resting and activated human monocytes.
Authors: S P Scully, G B Segel, M A Lichtman
Journal: Journal of Clinical Investigation (1984)

We have performed a comprehensive study of calcium tracer flux, distribution, content, and ionized cytoplasmic calcium during monocyte activation. A model of monocyte calcium was developed from 45Ca uptake and exodus curves which indicated that cell calcium was partitioned between three compartments. The magnitude of the time constants for each pool lead us to propose cellular locations for these three compartments: a surface plasma membrane pool, a cytoplasmic pool, and an organelle pool. 45Ca uptake and exodus experiments were analyzed using a nonlinear least squares fit of compartmental exchange rates and sizes. The production of superoxide was used as a reflection of the state of activation of the monocytes treated with Concanavalin A (Con A). We found that Con A-treated monocytes have an increase in the calcium exchange rate with the cytoplasmic pool from 0.04 to 0.07/min (P less than 0.05), and an increase in the size of the cytoplasmic pool from 0.08 to 0.13 pmol/cell (P less than 0.05). There were no significant changes in the exchange rates or sizes associated with either of the other two compartments. The cytoplasmic ionized calcium was measured with the fluorescent probe, Quin 2, which indicated a resting level of 83 nM free calcium in unadhered monocytes. Con A stimulation caused a doubling of the cytoplasmic free calcium to 163 nM within 45 s. This increment in cytoplasmic free calcium preceded the onset of superoxide following Con A treatment. These studies indicate that Con A binding to the plasma membrane increases the monocyte plasma membrane permeability to calcium. External calcium enters the cell at an increased rate and contributes to both internally bound and free calcium. The magnitude of the increase in free calcium is proportional to the concentration of Con A and stimulates calcium extrusion via the calcium transport ATPase. Moreover, there is an increased concentration of ionized cytoplasmic calcium which has the potential to interact with other cellular regulators that modulate cell activation and superoxide production.
Oxidative Stress and p53 Mutations in the Carcinogenesis of Iron Overload-Associated Hepatocellular Carcinoma
Authors: A. J. Marrogi, M. A. Khan, H. E. van Gijssel, J. A. Welsh, H. Rahim, A. J. Demetris, K. V. Kowdley, S. P. Hussain, J. Nair, H. Bartsch, N. Okby, M. C. Poirier, K. G. Ishak, C. C. Harris
Journal: JNCI Journal of the National Cancer Institute (2001)
Paediatric respiratory mortality: past triumphs, future challenges
Authors: G Russell
Journal: Thorax (2005)

Radical new ideas are needed to ensure that deaths from respiratory diseases in children continue to fall

The invitation to comment on a paper that reports changes which occurred during a period that coincided, within a year or two, with my career as a consultant paediatrician presents me with an irresistible temptation to reminisce. At medical school in the late 1950s I learned that pneumonia, one time captain of the men of death, had responded dramatically first to sulphonamides and then to penicillin, but that some deaths were still “inevitable”—a phrase much used at that time to excuse our inability to manage conditions that we did not fully understand. Asthma was common in children but was considered to be an unusual cause of death, although it was responsible for the first death I encountered as a paediatric senior house officer. In the minds of my teachers asthma was readily distinguished from bronchitis and, to this day, I can replicate a table listing the differences between asthma and wheezy bronchitis, most of which has—to my surprise—turned out to be accurate.1 In those far off days most children with cystic fibrosis (CF) died in the pre-school years; Pseudomonas species were not the problem they are now and most children died while still colonised with Staphylococcus aureus or Haemophilus influenzae . Bronchiolitis was considered to be rather an esoteric diagnosis for which there was no diagnostic test – it would be a few years before its association with the respiratory syncytial virus (RSV) was appreciated.2 It was thought safer to diagnose pneumonia if crackles were prominent and to treat the child with antibiotics, while those with predominant wheeze were labelled “bronchitis” and given ephedrine.

In the mid 1960s I extracted data from the Registrar General’s annual reports when, as a junior, …
Safety of Statins
Authors: Stefano Bellosta, Rodolfo Paoletti, Alberto Corsini
Journal: Circulation (2004)

Statin monotherapy is generally well tolerated, with a low frequency of adverse events. The most important adverse effects associated with statins are myopathy and an asymptomatic increase in hepatic transaminases, both of which occur infrequently. Because statins are prescribed on a long-term basis, however, possible interactions with other drugs deserve particular attention, as many patients will typically receive pharmacological therapy for concomitant conditions during the course of statin treatment. This review summarizes the pharmacokinetic properties of statins and emphasizes their clinically relevant drug interactions.
Cost effectiveness of continuing professional development in health care: a critical review of the evidence
Authors: C A Brown
Journal: BMJ (2002)

Continuing professional development (CPD) for healthcare professionals is an important strategic instrument for improving health. The Department of Health identifies CPD as a way of maintaining standards of care; improving the health of the nation; and recruiting, motivating, and retaining high quality staff.1 To this end, direct NHS spending on continuing professional development in 1999-2000 was about £1bn ($1.6bn). 2 3 If we regard CPD as any method to improve health professionals' skills the total resources devoted to it are probably much greater, particularly with the recent increased participation in response to the need for recertification and revalidation.4 To ensure the maximum gain from participation in CPD, these resources must be used efficiently.

To assess the efficiency of participating in CPD, economic criteria are needed. Resources for health care are scarce, and money spent on CPD could otherwise be used for direct patient care. These opportunity costs are explicitly considered in the economic methods of cost benefit analysis and cost effectiveness analysis. The literature contains various reviews of cost effectiveness analysis in both health care 5 6 and education.7 Such articles explain why cost effectiveness analysis (or another method of economic evaluation) is essential and how such evaluation should be undertaken, and they clearly define the set of economic terms (such as cost benefit analysis, cost effectiveness analysis, rate of return, and opportunity cost) that need to be incorporated into this type of research. Casebeer et al highlighted the need for economic evaluation of CPD activities,8 but they emphasised the use of cost benefit analysis, which requires monetary values to be assigned to measures of effectiveness. Cost benefit analysis is generally used to ascertain whether an intervention should be undertaken. Cost effectiveness analysis is used to decide which interventions (out of a number of alternatives) should …
The Longitudinal Course of Thought Disorder in Geriatric Patients With Chronic Schizophrenia
Authors: Christopher R. Bowie, Irene Tsapelas, Joseph Friedman, Michael Parrella, Leonard White, Philip D. Harvey
Journal: American Journal of Psychiatry (2005)

This study longitudinally assessed previously validated dimensions of thought disorder--verbal underproductivity and disconnection--in geriatric schizophrenia and replicated previous cross-sectional differences in communication disorders.Two hundred twenty patients with chronic schizophrenia were assessed with the Thought, Language, and Communication Scale over a mean follow-up period of 2.3 years.Patients had increases in verbal underproductivity but stable scores on disconnection over the follow-up period. Worsening in verbal underproductivity was associated with concurrent worsening in Mini-Mental State Examination scores and older age at baseline.Verbal underproductivity worsens with aging and is associated with cognitive worsening, although disconnected speech is relatively stable. Some geriatric patients with schizophrenia may lose the skills necessary to report symptoms, leading to the impression that their clinical status is improving.
INTESTINAL OBSTRUCTION
Authors: Lester R. Dragstedt, James J. Moorhead, Fred W. Burcky
Journal: The Journal of Experimental Medicine (1917)

1. Closed intestinal loops in which bacteria are first removed are compatible with life. 2. Closed intestinal loops in which bacteria are present but in which tissue necrosis is prevented, are compatible with life. 3. Closed aseptic intestinal loops in which the blood supply is completely occluded are compatible with life. 4. The normal secretions and bacterial products of the duodenum and jejunum are not sufficiently toxic to produce any symptoms when allowed to drain into the abdominal cavity. 5. Our results do not support the theory of Draper of a normal toxic secretion of the duodenal mucosa, neutralized by the jejunal mucosa, or the perverted secretion theory of Whipple. 6. Bacterial activity plus necrotic tissue, or the absorption of toxic products resulting from the action of putrefactive bacteria on necrotic tissue is the important factor in the rapid death in simple closed intestinal loops.
Tumor epidermal growth factor receptor studies in patients with non-small-cell lung cancer or head and neck cancer treated with monoclonal antibody RG 83852.
Authors: R Perez-Soler, N J Donato, D M Shin, M G Rosenblum, H Z Zhang, C Tornos, H Brewer, J C Chan, J S Lee, W K Hong
Journal: Journal of Clinical Oncology (1994)

PURPOSE Tumor tyrosine kinase activity associated with the epidermal growth factor receptor (EGFR) and localization of anti-EGFR monoclonal antibody RG 83852 were studied in patients with non-small-cell lung cancer (NSCLC) and head and neck cancer. PATIENTS AND METHODS Fifteen patients were treated with escalating doses of RG 83852 by continuous intravenous infusion for 5 days. Fresh tumor specimens were obtained 24 hours after therapy in 10 patients (of whom five had a pretherapy sample taken). Tumor EGFR tyrosine kinase activity was determined in fresh tumor samples by autophosphorylation of EGFR isolated in immunocomplexes with RG 83852. Tumor EGFR saturation with RG 83852 was assessed semiquantitatively by comparing the EGFR tyrosine kinase activity in immunocomplexes of tumor specimens obtained after therapy with total EGFR tyrosine kinase activity assessed by exogenous addition of RG 83852 to tumor lysates. Modulation of EGFR tyrosine kinase activity after the administration of RG 83852 was assessed by comparing EGFR tyrosine kinase activity from the same malignant lesion obtained before and after therapy. Tumor localization of RG 83852 and EGFR saturation were also assessed by immunohistochemistry. RESULTS No significant side effects were observed up to a total dose of 600 mg/m2. Based on tyrosine kinase activity, a high degree of EGFR saturation (&gt; or = 50%) was observed at doses &gt; or = 200 mg/m2, and EGFR saturation was estimated to be 100% at a dose level of 600 mg/m2 both in tumor tissue and skin used as surrogate EGFR-positive tissue. Immunohistochemistry studies showed that RG 83852 localized in tumor tissue and skin, but not in stroma, at doses &gt; or = 400 mg/m2, and high EGFR saturation was observed at 600 mg/m2. Tumor EGFR tyrosine kinase activity was studied in five patients (four with EGFR-positive tumors) before and 24 hours post-therapy; a threefold to fourfold upregulation of EGFR tyrosine kinase activity in posttherapy specimens was observed in two patients. Moderate upregulation of EGFR itself was suggested in both of these patients and in two additional patients by immunohistochemistry. CONCLUSION RG 83852 causes no toxic effects at doses that result in high tumor EGFR saturation. Treatment with RG 83852 may enhance EGFR tyrosine kinase activity and/or EGFR expression. Because high EGFR expression by tumors has been associated with increased sensitivity to cytotoxic therapy, the suggestion of antibody-mediated upregulation of EGFR by agents such as RG 83852 may prove useful in enhancing chemotherapeutic efficacy.
Concentration of Dihydrotestosterone and 3α-Androstanediol in Naturally Occurring and Androgen- Induced Prostatic Hyperplasia in the Dog
Authors: Ronald J. Moore, John M. Gazak, James F. Quebbeman, Jean D. Wilson
Journal: Journal of Clinical Investigation (1979)

Previous studies have suggested that dihydrotestosterone accumulation in the prostate may be involved in the pathogenesis of prostatic hyperplasia in man and dog. However, the fact that the administration of 10 mg dihydrotestosterone/d to castrated, mongrel dogs (0.5 mg/kg body wt) causes little growth in the prostate, whereas identical doses of 3α- androstanediol regularly induce prostatic hyperplasia (> 14 g weight) has raised the possibility that the dihydrotestosterone accumulation may be the result rather than the cause of the pathology. To investigate the mechanism of this phenomenon, we measured the levels of dihydrotestosterone and 3α-androstanediol in prostates from 75 dogs. In both naturally occurring and 3α-androstanediol-induced prostatic hyperplasia, the levels of dihydrotestosterone were high (>5 ng/g), whereas in immature glands and glands from dihydrotestosterone-treated animals, levels were similar (2.1 and 2.6 ng/g, respectively). 3α-Androstanediol levels were no different in animals treated with dihydrotestosterone or 3α-androstanediol.
A New Tumor Suppressor DnaJ-like Heat Shock Protein, HLJ1, and Survival of Patients With Non–Small-Cell Lung Carcinoma
Authors: Meng-Feng Tsai, Chi-Chung Wang, Gee-Chen Chang, Chih-Yi Chen, Hsuan-Yu Chen, Chiou-Ling Cheng, Yu-Ping Yang, Chun-Yi Wu, Fu-Yuan Shih, Chun-Chi Liu, Hsiu-Ping Lin, Yuh-Shan Jou, Shu-Chen Lin, Chung-Wu Lin, Wei J. Chen, Wing-Kai Chan, Jeremy J. W. Chen, Pan-Chyr Yang
Journal: JNCI Journal of the National Cancer Institute (2006)

We previously identified DnaJ-like heat shock protein (HLJ1) as a gene associated with tumor invasion. Here, we investigated the clinical significance of HLJ1 expression in non-small-cell lung cancer (NSCLC) patients and its role in cancer progression.We induced HLJ1 overexpression or knockdown in human lung adenocarcinoma CL1-5 cells and analyzed cell proliferation, anchorage-independent growth, in vivo tumorigenesis, cell motility, invasion, and cell cycle progression. Expression of genes that act downstream of HLJ1 was examined by DNA microarray analysis, pathway analysis, and western blotting. We measured HLJ1 expression in tumors and adjacent normal tissues of 71 NSCLC patients by quantitative reverse transcription-polymerase chain reaction. Associations between HLJ1 expression and disease-free and overall survival were determined using the log-rank test and multivariable Cox proportional hazards regression analysis. Validation was performed in an independent cohort of 56 NSCLC patients. Loss of heterozygosity (LOH) mapping of the HLJ1 locus was analyzed in 48 paired microdissected NSCLC tumors. All statistical tests were two-sided.HLJ1 expression inhibited lung cancer cell proliferation, anchorage-independent growth, tumorigenesis, cell motility, and invasion, and slowed cell cycle progression through a novel STAT1/P21(WAF1) pathway that is independent of P53 and interferon. HLJ1 expression was lower in tumors than in adjacent normal tissue in 55 of 71 patients studied. NSCLC patients with high HLJI expressing tumors had reduced cancer recurrence (hazard ratio [HR] = 0.47; 95% confidence interval [CI] = 0.23 to 0.93; P = .03) and longer overall survival (HR = 0.38; 95% CI = 0.16 to 0.89; P = .03) than those with low-expressing tumors. Validation in the independent patient cohort confirmed the association between HLJ1 expression and patient outcome. LOH mapping revealed high frequencies (66.7% and 70.8%) of allelic loss and microsatellite instability (87.5% and 95.2%) of the HLJ1 locus at chromosome 1p31.1.HLJ1 is a novel tumor suppressor in NSCLC, and high HLJ1 expression is associated with reduced cancer recurrence and prolonged survival of NSCLC patients.
Flexible bronchoscopy in children with neuromuscular disease and acute hypoxemic respiratory failure requiring noninvasive ventilation
Authors: Uros Krivec, Marina Praprotnik, Dusanka Lepej, Ana Kotnik Pirs, Jelena Berger
Journal: European Respiratory Journal (2014)

Introduction   Lower respiratory tract infections (LRTI) are frequently complicated by lung collapse in children with neuromuscular diseases (NMD). Both conditions predispose to acute respiratory failure and endotracheal intubation (EI). Bronchoscopic aspiration and noninvasive positive pressure ventilation (NIV) had been reported effective in adult patients.   Aims   To evaluate feasibility & safety of flexible bronchoscopy (FB) and NIV in children with NMD with lung collapse and acute hypoxemic respiratory failure. The need for EI and atelecasts resolution were assessed.   Methods   8 consecutive patients with NMD, LRTI and atelectasis were included. Median age 3.2 years, range 2.4-16.5 years. One had spinal muscular atrophy (SMN) type 1, 4 had SMN type 2, 2 had Duchenne muscular dystrophy. 5 children were already on home NIV. 1 was hospitalized twice. Treatment protocol consisted of: admission to high dependency unit, FB aspiration under general anesthesia, NIV during and after FB, intensive respiratory physiotherapy (cough assist).   Results   All patients required additional oxygen and had marked respiratory distress on admission. 6 were treated by the full protocol; in 2 cases FB was not performed. Mean hospital stay was 8.8 (± 1.9) days. None needed EI; one had a transient intensive care stay after FB. At discharge, re-expansion of collapsed lungs was seen in all cases with full protocol performed but not in the 2 patients without aspiration.   Conclusions   FB aspiration in children with NMD requiring NIV for acute respiratory failure is feasible and safe in adequate settings. The protocol appears effective in promoting atelectasis re-expansion.
ALVEOLAR AND ARTERIAL OXYGEN TENSIONS AND THE SIGNIFICANCE OF THE ALVEOLAR-ARTERIAL OXYGEN TENSION DIFFERENCE IN NORMAL MEN 1
Authors: Giles F. Filley, Fernand Gregoire, George W. Wright
Journal: Journal of Clinical Investigation (1954)

We have had two objectives in determining al- veolar and arterial oxygen tensions.It was hoped that they might be sensitive criteria for the normal- ity of pulmonary oxygen transfer in health and disease.Secondly, a study of these oxygen tension values together with other respiratory measure- ments might further elucidate the process by which pulmonary artery blood becomes oxygenated as it perfuses the lung.The purposes of this paper are: 1.To examine the validity and accuracy of the methods by which alveolar Po2 is determined, the technique for esti- mating arterial Po2 and Pco2 having been criti- cally discussed elsewhere (1). 2. To present the data from which the alveolar-arterial oxygen ten- sion difference has been calculated in a group of normal men breathing atmospheric air.3. To discuss the significance of this difference in the resting and exercise state.The Validity and Accuracy of the Method for Calculating Alveolar PO,
Dancing With Many Different Ghosts
Authors: Heather J. Dean
Journal: Diabetes Care (2002)

My training in the treatment of type 2 diabetes in children began when my father recounted stories of his experience in northern Canada as a fur trader with the Hudson’s Bay Company (HBC) in the 1930s. The Cree people lived in tents in the winter months and took them down in the summer and fall to go out on the land to hunt. The HBC store traded fur pelts for flour, lard, and saccharine (sugar was much too expensive). Later, in the 1970s, as a medical student on an elective in northern communities, the itinerant dentist talked of the frustration at having to do so many dental extractions in young children with rotten teeth. My early “diabetes” training was continuing with the stories told by the pregnant women who sat for hours together carving soapstone behind the hospital. The women had “come out” from their communities to wait until after delivery before returning home. They talked of their hardships and sorrows, their children and families, and living off the land.

I’ve also learned from our northern outreach clinics. We fly in small planes to small communities surrounded by rock, lakes, rivers, and boreal forest. After our afternoon clinics, we walk to the store along the frozen barren roads in winter or the potholed, dust-covered roads shared with pickup trucks in spring. Several youth from our clinic show up. We walk around the aisles together as a group—the teens, doctor, dietitian, nurse, and social worker. We read labels of snack foods and compare prices of fresh, frozen, and canned products. Elders express their concern about diabetes in their community and especially about the fate of the children. We scrutinize the checkout counter to see how many cartons of soda pop and chips are going through. We learn that two of the …
Abstract 4198: MiR-17-92 cluster promotes human cholangiocarcinoma growth upon the activation of STAT3 signaling pathway.
Authors: Hanqing Zhu, Chang Han, Tong Wu
Journal: Cancer Research (2013)

Abstract MiR-17-92 cluster is a potent oncogenic miRNA which has been shown to promote cell proliferation, increase angiogenesis and sustain cell survival in several cancer types. However, the potential role of miR-17-92 cluster in hepatic carcinogenesis has not been investigated. This study was designed to examine the impact of miR-17-92 in hepatic cancer cells. qRT-PCR analysis showed that the expression of miR-17-92 cluster is increased in several human hepatic cancer cell lines compared to the transformed, non-cancerous hepatic cell line, THLE-2. In addition to that, paraffin slides from human hepatic cancer sample also show higher expression of miR-19a as a result of in situ hybridization. The miR-17-92 inhibitors (blocking each individual miRNAs within the cluster) prevented hepatic cancer cell growth. In contrast, stable transfection of pri-miR-17-92 cluster increased cholangiocarcinoma cell (CCLP-1) proliferation. IL-6 treatment greatly upregulates the miR-17-92 cluster mRNA and each individual miRNA level. However, blocking IL-6/STAT3 signaling by STAT3 siRNA or STAT3 phosphorylation inhibitor both inhibit upregulation of miR-17-92 by IL-6 stimulation. Since there is a reported binding site on promoter region of miR-17-92 cluster for STAT3, we used synthesized DNA probe to precipitate STAT3, and found IL-6 treatment increases the STAT3 binding to the promoter of miR-17-92. IL-6 stimulates CCLP-1cell growth, but blocking miR-17-92 will abolish this effect. Targetscan and other prediction tools were used to predict many possible targets of miR-17-92, such as PTEN. Western blot analysis showed decreased PTEN protein level in CCLP-1 cells transfected with the pri-miR-17-92 cluster, suggesting that PTEN may represent one of the miR-17-92 downstream targets. Further experiments are undergoing to show the IL-6 activates STAT3 and thus promote cholangiocarcinoma cell growth through increasing miR-17-92 cluster level. Citation Format: Hanqing Zhu, Chang Han, Tong Wu. MiR-17-92 cluster promotes human cholangiocarcinoma growth upon the activation of STAT3 signaling pathway. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4198. doi:10.1158/1538-7445.AM2013-4198