tbuckley/cabot-search huggingface dataset:
Low-density lipoprotein uptake and cholesterol accumulation by cultured renal cells.
Authors: S Hashimoto, G T Nagami
Journal: Journal of the American Society of Nephrology (1991)

The uptake of low-density lipoprotein (LDL) and the accumulation of cholesterol were assessed in opossum kidney (OK) and Madin-Darby canine kidney (MDCK) cells. OK and MDCK cells were grown to confluency on Millicell well inserts. The uptake of human LDL across the apical and basolateral surfaces of OK and MDCK cells was assessed by the degradation of internalized (125I)LDL to trichloroacetic acid-soluble products. LDL uptake via the apical surface of OK cells increased linearly with LDL concentration, indicating nonreceptor-mediated uptake. In contrast, LDL uptake via the basolateral surface of OK cells and both apical and basolateral surfaces of MDCK cells followed a saturable pattern. In addition, (125I)LDL bound to the apical membrane of MDCK cells, but not to the apical membrane of OK cells, was displaced by heparin and by excess of unlabeled LDL. Exposure to LDL (100 mg/mL) resulted in an increase in total cholesterol content of OK and MDCK cells (23 and 18%, respectively). Most of the increase in total cholesterol content with LDL exposure resulted from increased free cholesterol content in MDCK cells and esterified cholesterol in OK cells. The differences in cholesteryl ester formation were consistent with the slower rates of (14C) oleate incorporation into cholesteryl ester and lower cholesterol esterifying activity observed in MDCK cells compared with that in OK cells. These results demonstrate that LDL uptake can be receptor or nonreceptor mediated, depending upon the renal cell type and the surface exposed to LDL, and that LDL exposure leads to increased cholesterol content in OK and MDCK cells.
Acute effects of a single open sea air dive and post-dive posture on cardiac output and pulmonary gas exchange in recreational divers
Authors: Z Dujic, D Bakovic, I Marinovic-Terzic, D Eterovic
Journal: British Journal of Sports Medicine (2005)

To evaluate the cardiopulmonary effects of open sea scuba air diving to 39 m (30 minutes bottom time) with standard decompression. To account for possible gravity dependent effects of venous gas bubbles, the variables were measured in different post-dive body postures and compared with the baseline values before the dive in the same posture.Eight male divers conducted two similar dives on successive days. Their posture before and after the dive was either sitting or supine, in random order. The divers were evaluated before and 30, 60, and 90 minutes after the dive. Venous bubbles were detected by precordial Doppler after the dive in four divers in the supine posture and two divers in the sitting posture.Arterialised oxygen tension had decreased at all times after the dive (-11.3 mm Hg, p = 0.00006), due to decreased alveolar oxygen tension, irrespective of posture. Apart from an increase in the sitting posture 30 minutes after the dive, pulmonary capacity for carbon monoxide diffusion and cardiac index decreased, mostly 60 minutes after the dive (-9%, p = 0.0003 and -20%, p = 0.0002 respectively). The decrease in cardiac index was greater in the supine posture (p = 0.0004), and the physiological dead space/tidal volume ratio increased more in the sitting position (p = 0.006).Field dives are associated with moderate impairments in cardiac output and gas exchange. Some of these impairments appear to depend on the posture of the diver after the dive.
Loss of Immunity Against Vaccinia After Attack of Variola Minor
Authors: J. P. Marsden
Journal: BMJ (1964)

Medical Memoranda MEDIOALfrom behind the right pole of the thyroid gland.The patient died suddenly nine hours after operation when the serum calcium was still 19 mg./100 ml.Histologically the tumour was a chief-cell parathyroid adenoma.At necropsy there was widespread fat necrosis due to acute pancreatitis and thrombosis of the splenic, left common iliac, and femoral veins.Thrombus occluded the left renal vein to 1 cm.from the inferior vena cava.There was metastatic calcification in the tubules of both kidneys but no involvement of the smaller renal veins by thrombosis. COMMENTIn acute hyperparathyroidism there has been little documenta- tion of thrombosis occurring in the venous system.Smith and Cooke (1940) reported a case of hypercalcaemia due to para- thyroid adenoma in which bilateral renal vein thrombosis was discovered at necropsy.Horowitz and Berenbaum (1958) report the case of a 17-year-old girl who had ante-mortem thrombus in the left main renal and ovarian vein.Stampfl (1963) has described four cases of renal-vein thrombosis in acute hyperparathyroidism.Renal-vein thrombosis may cause either nephrotic syndrome or progressive oliguric renal failure (Harrison, Milne, and Steiner, 1956), but in the absence of inferior vena caval obstruction it is usually associated with primary renal disease.In the cases reported here the primary renal damage was presumably the hypercalcaemic effect on the tubules (Epstein, 1960).In severe hyperparathyroidism there may also be a decrease in the renal plasma flow (Edvall, 1958) and an increased risk of stagnation in the renal veins.This may be aggravated by increased viscosity of the blood due to the salt and water depletion that was clinically present in both our patients and was probably due to renal losses in the presence of hypercalcaemia.The patients demonstrate many of the other features pre- viously described in hyperparathyroidism: mental changes,
P01.08 * LINEAGE-SPECIFIC SPLICING OF AN ALTERNATIVE EXON OF ANXA7 PROMOTES EGFR SIGNALING ACTIVATION AND TUMOR PROGRESSION IN GLIOBLASTOMA
Authors: R. Ferrarese, E. Bug, D. Maticzka, W. Reichardt, A. P. Masilamani, F. Dai, A. Weyerbrock, M. Prinz, M. Bredel, M. S. Carro
Journal: Neuro-Oncology (2014)

Tissue-specific alternative splicing is critical to the emergence of tissue identity during development, yet its role in malignant transformation is undefined. Tissue-specific splicing involves evolutionarily-conserved, alternative exons, which represent only a minority of total alternative exons. Many, however, have functional features that influence signaling pathways to profound biological effect. In the brain, Annexin A7 isoform 1 (ANXA7-I1) is exclusively expressed in mature neurons, while isoform 2 (ANXA7-I2) in which exon 6 is skipped, is expressed in glial and progenitor cells. We show that lineage-specific splicing of the cassette exon 6 in the membrane-binding tumor suppressor ANXA7diminishes endosomal targeting and consequent signal termination of the EGFR oncoprotein during brain tumor progression. Splicing of this exon is mediated by Polypyrimidine Tract-Binding Protein 1 (PTBP1), a ribonucleoprotein normally repressed during neuronal development but which we found to be highly expressed also in glioblastomas through loss of a brain-enriched microRNA, miR-124, and gene amplification. Here, we show that the PTBP1-ANXA7 splicing-EGFR signal activation axis promotes in vitro cell migration and invasion, and tumor angiogenesis in vivo. In glioblastoma, ANXA7 splicing is likely inherited from a potential tumor-initiating ancestor but this trait is further exploited through accumulation of mutations that enhance EGFR signaling. Our data illustrate how lineage-specific splicing of a tissue-regulated alternative exon in a constituent of an oncogenic pathway eliminates its tumor suppressor function and promotes glioblastoma progression. This paradigm may offer a general model as to how tissue-specific regulatory mechanisms can contribute to reprogramming normal development to oncogenesis.
Rapid metagenomic identification of viral pathogens in clinical samples by real-time nanopore sequencing analysis
Authors: Alexander L. Greninger, Samia N. Naccache, Scot Federman, Guixia Yu, Placide Mbala, Vanessa Bres, Doug Stryke, Jerome Bouquet, Sneha Somasekar, Jeffrey M. Linnen, Roger Dodd, Prime Mulembakani, Bradley S. Schneider, Jean-Jacques Muyembe-Tamfum, Susan L. Stramer, Charles Y. Chiu
Journal: Genome Medicine (2015)

We report unbiased metagenomic detection of chikungunya virus (CHIKV), Ebola virus (EBOV), and hepatitis C virus (HCV) from four human blood samples by MinION nanopore sequencing coupled to a newly developed, web-based pipeline for real-time bioinformatics analysis on a computational server or laptop (MetaPORE). At titers ranging from 10(7)-10(8) copies per milliliter, reads to EBOV from two patients with acute hemorrhagic fever and CHIKV from an asymptomatic blood donor were detected within 4 to 10 min of data acquisition, while lower titer HCV virus (1 × 10(5) copies per milliliter) was detected within 40 min. Analysis of mapped nanopore reads alone, despite an average individual error rate of 24 % (range 8-49 %), permitted identification of the correct viral strain in all four isolates, and 90 % of the genome of CHIKV was recovered with 97-99 % accuracy. Using nanopore sequencing, metagenomic detection of viral pathogens directly from clinical samples was performed within an unprecedented <6 hr sample-to-answer turnaround time, and in a timeframe amenable to actionable clinical and public health diagnostics.
Pathophysiological roles of nuclear factor kappaB (NF-kB) in pulmonary arterial hypertension: effects of synthetic selective NF-kB inhibitor IMD-0354
Authors: Susumu Hosokawa, Go Haraguchi, Akihito Sasaki, Hirokuni Arai, Susumu Muto, Akiko Itai, Shozaburo Doi, Shuki Mizutani, Mitsuaki Isobe
Journal: Cardiovascular Research (2013)

Proliferation of pulmonary arterial smooth muscle cells (PASMCs) is one histological sign of pulmonary arterial hypertension (PAH). We hypothesized that a signalling cascade from fibroblast growth factor 2 (FGF2) to plasminogen activator inhibitor 1 (PAI-1) and monocyte chemotactic protein-1 (MCP-1) via nuclear transcription factor nuclear factor kappaB (NF-kB) play a critical role in progression of PAH, and tested this hypothesis both in vivo and in vitro using a synthetic selective NF-kB inhibitor, N-(3,5-Bis-trifluoromethyl-phenyl)-5-chloro-2-hydroxy-benzamide (IMD-0354). Monocrotaline (MCT) was injected into 75 Sprague–Dawley rats. Starting at day 14 after MCT injection, we administered IMD-0354 (MCT + IMD group) or vehicle (MCT group) daily. At day 32, 65% of the MCT + IMD group were alive compared with 0% of the MCT group. IMD-0354 prevented increase of right ventricular pressure, and suppressed proliferation and induced apoptosis of PASMCs. mRNA transcript levels of FGF2, PAI-1, and tissue plasminogen activator (t-PA) were lower in MCT + IMD compared with MCT. In in vitro experiments, IMD-0354 inhibited p65 translocation to the nucleus promoted by FGF2 in PASMCs. Furthermore, the time courses of extracellular signal-regulated kinase (Erk) 1/2, MCP-1, and PAI-1 stimulated with FGF2 were each markedly shortened by IMD-0354. We speculate that the positive-feedback loop (Erk1/2–NF-kB–MCP-1–Erk1/2) is associated with progression of PAH by causing FGF2-induced inflammation in MCT rats. IMD-0354 has potential as a new therapeutic tool for PAH.
BP, Cardiovascular Disease, and Death in the Folic Acid for Vascular Outcome Reduction in Transplantation Trial
Authors: Myra A. Carpenter, Alin John, Matthew R. Weir, Stephen R. Smith, Lawrence Hunsicker, Bertram L. Kasiske, John W. Kusek, Andrew Bostom, Anastasia Ivanova, Andrew S. Levey, Scott Solomon, Todd Pesavento, Daniel E. Weiner
Journal: Journal of the American Society of Nephrology (2014)

The optimal BP level in kidney transplant recipients remains uncertain. This post hoc analysis of the Folic Acid for Vascular Outcome Reduction in Transplantation (FAVORIT) trial cohort assessed associations of BP with a pooled cardiovascular disease (CVD) outcome and with all-cause mortality. In 3474 prevalent kidney transplant patients, mean age was 52±9 years, 63% were men, 76% were white, 20% had a history of CVD, 40% had a history of diabetes mellitus, and the median time since transplant was 4.1 years (25th to 75th percentiles, 1.7-7.4); mean systolic BP was 136±20 mmHg and mean diastolic BP was 79±12 mmHg. There were 497 CVD events and 406 deaths. After adjustment for demographic and transplant characteristics and CVD risk factors, each 20-mmHg increase in baseline systolic BP associated with a 32% increase in subsequent CVD risk (hazard ratio [HR], 1.32; 95% confidence interval [95% CI], 1.19 to 1.46) and a 13% increase in mortality risk (HR, 1.13; 95% CI, 1.01 to 1.27). Similarly, after adjustment, at diastolic BP levels<70 mmHg, each 10-mmHg decrease in diastolic BP level associated with a 31% increase in CVD risk (HR, 1.31; 95% CI, 1.06 to 1.62) and a 31% increase in mortality risk (HR, 1.31; 95% CI, 1.03 to 1.66). However, at diastolic BP levels>70 mmHg, there was no significant relationship between diastolic BP and outcomes. Higher systolic BP strongly and independently associated with increased risk of CVD and all-cause mortality, without evidence of a J shape, whereas only lower levels of diastolic BP associated with increased risk of CVD and death in this trial.
Coronary aneurysms in patients with autosomal dominant polycystic kidney disease.
Authors: H Hadimeri, C Lamm, G Nyberg
Journal: Journal of the American Society of Nephrology (1998)

Patients with autosomal dominant polycystic kidney disease (ADPKD) have an increased risk of intracranial aneurysms. Reports on arterial aneurysms in other locations have not been conclusive. The present study was initiated to investigate the prevalence of coronary aneurysms. Thirty ADPKD patients who had undergone coronary angiography on clinical indication were identified, 15 after renal transplantation. For each ADPKD patient, a control patient was identified with end-stage renal disease, investigated by coronary angiography, and matched for age, sex, and time relation to transplantation. All angiograms were retrieved and reevaluated with respect to aneurysms, defined as an increase in artery diameter by 50% or more, as well as to pathologic ectasias not fulfilling this criterion. Aneurysms were detected in four ADPKD patients and two control subjects. Five more ADPKD patients, but none of the control subjects, had minor ectasias. One ADPKD patient had a dissecting aortic aneurysm, and another died of aortic dissection during bypass surgery. This study adds to the evidence of an increased risk of extracranial aneurysms in ADPKD patients.
Management and short-term outcomes of non-traumatic pneumothorax (PT) in a department of respiratory medicine
Authors: Ulrik Iepsen, Thomas Ringbaek
Journal: European Respiratory Journal (2013)

Background: The knowledge of management strategies for non-traumatic PT is sparse.

Aim: To compare the efficacy and complications of surgical (large-bore) chest tube drainage with smaller chest tubes inseted by Seldinger technique in patients with non-traumatic PT.

Methods: A retrospective study of all patients admitted to Hvidovre Hospital, DK, with non-traumatic PT between 01.04.2009 and 31.12.2011. During regular hours (08.00-15.00) on weekdays non-traumatic PTs are managed by chest physicians and by orthopedic surgeons the remaining hours. Chest physicians used Seldinger technique. In general, a True-Close thoracic vent with Heimlich valve, size Fr11-13, while surgeons used chest tubes, size Fr20-28, inserted though a small thoracotomy. Data were analyzed for overall trends and differences in demographic data and short-term outcomes such as complications, duration of drainage time and duration of hospital stay.

Results: In total, 104 episodes of PT were analyzed: 62 PSP, 30 SSP, and 12 iatrogenic PT. An overall incidence of PT was 10/100,000. There were no differences between patients, type of PT, or size of PT comparing the 62 episodes managed by surgeons with the 42 episodes managed by chest physicians.

Patients with large-bore drains managed by surgeons had more complications (33.3% vs 14.5%; P=0.026), lower success rate at primary tube placement (56.5% vs 85.7%; P=0.002) and longer hospital stays (11.8 vs 6.9 days; P=0.004) than patients treated with smaller chest tubes.

Conclusion: Our results support the BTS guidelines in recommending minimal invasive approach in management of non-traumatic PT.
Economic benefits of vaccination need to be seen in wider context
Authors: B. Roehr
Journal: BMJ (2011)

Improvements in vaccines and their delivery could save the lives of an estimated 6.4 million children and prevent many disabilities over the next 10 years in the world’s 72 poorest countries, show new figures published in a Health Affairs focus issue on vaccines (http://content.healthaffairs.org/content/30/6.toc).

The cost of the vaccines is projected to be around $17bn (£10.4bn; €12bn) over 10 years, with additional funds needed to deliver them. But the savings in healthcare costs and greater economic productivity would far outweigh the costs, said Orin Levine, director of the International Vaccine Access Center of the Johns Hopkins Bloomberg School of Public Health, Baltimore.

“We need to move from a narrow view of the economic benefits of vaccination to a broader one,” he told a …
REPORTS
Authors: John S. Kovach, Renee M. McGovern, Joslyn D. Cassady, Selene K. Swanson, Lester E. Wold, Bert Vogelstein, Steve S. Sommer
Journal: JNCI Journal of the National Cancer Institute (1991)

A new technique for characterizing somatic mutations in very small samples of cellularly heterogeneous human cancer tissue was developed and tested using mutations in the p53 gene in breast carcinomas as a model system. The technique combines touch preparation of specimens to obtain homogeneous clusters of carcinoma cells free of normal cells with a nested pair of polymerase chain reaction (PCR) amplifications of DNA to increase the amount of target gene sequence sufficiently to permit direct sequencing of the p53 gene. Touch preparations of fresh or previously frozen tissue from human adenocarcinomas derived from several organs were stained, and clusters of 10-50 malignant cells were transferred by pipette into microfuge tubes for PCR amplification. Exons 5-9 of the p53 gene, which contain the major mutational hot spots associated with most human cancers, were sequenced by the following steps: 1) two rounds of PCR amplification using DNA Taq polymerase and two sets of oligonucleotide primers, the second set being nested within the segment amplified by the first set and having attached T7 and SP6 phage promoter sequences, 2) transcription of the amplified DNA sequences with T7 and SP6 RNA polymerases, and 3) dideoxy sequencing of single-stranded RNA transcripts with reverse transcriptase and with additional oligonucleotide primers to achieve specificity for this unique region of the genome. The utility of this approach is illustrated by our success in detecting and analyzing point mutations in cell clusters from four of 11 primary adenocarcinomas of the human breast.
Behaviour of 125I-fibrinogen and 131I-albumin in experimental galactosamine-induced hepatitis.
Authors: I Mahn, H Merkel, E L Sattler, G Muller-Berghaus
Journal: Gut (1977)

The turnover of 125I-labelled fibrinogen and 131I-labelled albumin was studied in the course of galactosamine-induced hepatitis in rabbits. In addition to galactosamine, some animals were treated with epsilon-aminocaproic acid (EACA) to inhibit the activation of the fibrinolytic system. The infusion of galactosamine and EACA caused generation of fibrin-rich microclots in the renal glomerular capillaries in seven out of 12 rabbits. Correspondingly, the incorporation of 125I-radioactivity into liver, spleen, and kidneys was pronounced in galactosamine- and EACA-treated rabbits compared with control animals treated with EACA. An acceleration of the 125I-fibrinogen elimination from the plasma was observed between eight and 12 hours after the start of the galactosamine infusion. The administration of heparin in addition to galactosamine and EACA prevented the occurrence of intravascular coagulation, but shortened the survival times of the animals because of bleeding into visceral organs. The elimination of 131I-albumin in plasma as well as the distribution of 131I-radioactivity in organs were similar in all the rabbits independent of the treatment with galactosamine, EACA, or heparin. The experiments indicate that, in addition to diminished synthesis of coagulation factors, disseminated intravascular coagulation is involved in galactosamine-induced hepatitis and contributes to the haemostatic disorder.
Hedgehog signaling in the liver
Authors: Alessia Omenetti, Steve Choi, Gregory Michelotti, Anna Mae Diehl
Journal: Journal of Hepatology (2010)

Reactivation of Hedgehog (Hh), a morphogenic signaling pathway that controls progenitor cell fate and tissue construction during embryogenesis occurs during many types of liver injury in adult. The net effects of activating the Hedgehog pathway include expansion of liver progenitor populations to promote liver regeneration, but also hepatic accumulation of inflammatory cells, liver fibrogenesis, and vascular remodeling. All of these latter responses are known to be involved in the pathogenesis of cirrhosis. In addition, Hh signaling may play a role in primary liver cancers, such as cholangiocarcinoma and hepatocellular carcinoma. Study of Hedgehog signaling in liver cells is in its infancy. Additional research in this area is justified given growing experimental and clinical data supporting a role for the pathway in regulating outcomes of liver injury.
Phase III Study of Cisplatin, Etoposide, and Concurrent Chest Radiation With or Without Consolidation Docetaxel in Patients With Inoperable Stage III Non–Small-Cell Lung Cancer: The Hoosier Oncology Group and U.S. Oncology
Authors: Nasser Hanna, Marcus Neubauer, Constantin Yiannoutsos, Ronald McGarry, James Arseneau, Rafat Ansari, Craig Reynolds, Ramaswamy Govindan, Anton Melnyk, William Fisher, Donald Richards, Daniel Bruetman, Thomas Anderson, Naveed Chowhan, Sreenivasa Nattam, Prasad Mantravadi, Cynthia Johnson, Tim Breen, Angela White, Lawrence Einhorn
Journal: Journal of Clinical Oncology (2008)

Concurrent chemoradiotherapy is standard treatment for patients with inoperable stage III non-small-cell lung cancer (NSCLC). A phase II study by the Southwest Oncology Group using consolidation docetaxel after cisplatin (P), etoposide (E), and radiation (XRT) resulted in a median survival time (MST) of 26 months. This randomized phase III trial evaluated whether consolidation docetaxel was responsible for this improved survival.Eligible patients had stage IIIA or IIIB NSCLC, baseline performance status of 0 to 1, forced expiratory volume in 1 second >or= 1 L, and less than 5% weight loss. Patients received P 50 mg/m(2) intravenously (IV) on days 1, 8, 29, and 36 and E 50 mg/m(2) IV on days 1-5 and 29-33 concurrently with chest XRT to 59.40 Gy. Patients who did not experience progression were randomly assigned to docetaxel 75 mg/m(2) IV every 21 days for three cycles versus observation. The primary end point was to compare overall survival (Kaplan-Meier analysis).On the basis of evidence of futility, a data and safety monitoring board recommended early termination after an analysis of the initial 203 patients. Patient characteristics (n = 203) were as follows: 34% female; median age, 63 years; 39.4% stage IIIA; and 60.6% stage IIIB. One hundred forty-seven (72.4%) of 203 patients were randomly assigned to docetaxel (n = 73) or observation (n = 74). Grade 3 to 5 toxicities during docetaxel included febrile neutropenia (10.9%) and pneumonitis (9.6%); 28.8% of patients were hospitalized during docetaxel (v 8.1% in observation arm), and 5.5% died as a result of docetaxel. The MST for all patients (n = 203) was 21.7 months; MST was 21.2 months for docetaxel arm compared with 23.2 months for observation arm (P = .883).Consolidation docetaxel after PE/XRT results in increased toxicities but does not further improve survival compared with PE/XRT alone in patients with stage III inoperable NSCLC.