tbuckley/cabot-search huggingface dataset:
Epithelial Stress and Apoptosis Underlie Hermansky-Pudlak Syndrome–associated Interstitial Pneumonia
Authors: Poornima Mahavadi, Martina Korfei, Ingrid Henneke, Gerhard Liebisch, Gerd Schmitz, Bernadette R. Gochuico, Philipp Markart, Saverio Bellusci, Werner Seeger, Clemens Ruppert, Andreas Guenther
Journal: American Journal of Respiratory and Critical Care Medicine (2010)

The molecular mechanisms underlying Hermansky-Pudlak syndrome-associated interstitial pneumonia (HPSIP) are poorly understood but, as in idiopathic pulmonary fibrosis, may be linked to chronic alveolar epithelial type II cell (AECII) injury.We studied the development of fibrosis and the role of AECII injury in various murine models of HPS.HPS1, HPS2, and HPS6 monomutant mice, and HPS1/2 and HPS1/6 double-mutant and genetic background mice, were killed at 3 and 9 months of age. Quantitative morphometry was undertaken in lung sections stained with hemalaun-eosin. The extent of lung fibrosis was assessed by trichrome staining and hydroxyproline measurement. Surfactant lipids were analyzed by electrospray ionization mass spectrometry. Surfactant proteins, apoptosis, and lysosomal and endoplasmic reticulum stress markers were studied by Western blotting and immunohistochemistry. Cell proliferation was measured by water-soluble tetrazolium salt-1 and bromodeoxyuridine assays.Spontaneous and slowly progressive HPSIP was observed in HPS1/2 double mutants, but not in other HPS mutants, with subpleural onset at 3 months and full-blown fibrosis at 9 months. In these mice, extensive surfactant abnormalities were encountered in AECII and were paralleled by early lysosomal stress (cathepsin D induction), late endoplasmic reticulum stress (activating transcription factor-4 [ATF4], C/EBP homologous protein [CHOP] induction), and marked apoptosis. These findings were fully corroborated in human HPSIP. In addition, cathepsin D overexpression resulted in apoptosis of MLE-12 cells and increased proliferation of NIH 3T3 fibroblasts incubated with conditioned medium of the transfected cells.Extensively impaired surfactant trafficking and secretion underlie lysosomal and endoplasmic reticulum stress with apoptosis of AECII in HPSIP, thereby causing the development of HPSIP.
Technetium-99m Diphosphonate Imaging of Psammocarcinoma of Probable Ovarian Origin
Authors: Arthur I. Radin, Irini M. Youssef, Ricardo D. Quimbo, Robert W. Perone, Claudio Guerrieri, Hussein M. Abdel-Dayem
Journal: Clinical Nuclear Medicine (2005)

Technetium-99m methylene diphosphonate (Tc-99m MDP) bone scans have long been used by clinicians to diagnose osseous metastases in patients with cancer. However, in several benign and malignant diseases, notably those characterized by extensive soft tissue calcification, Tc-99m MDP may be taken up by the tumor itself. We present a case of a stage IIIC psammoma-rich low-grade serous carcinoma of the ovary, whose identity and extent of disease were first suggested by Tc-99m MDP scintigraphy. The literature concerning this form of cancer, and the use of Tc-99m MDP bone scans to image soft tissue lesions, are reviewed.
Increased number and function of endothelial progenitor cells stimulate angiogenesis by resident liver sinusoidal endothelial cells (SECs) in cirrhosis through paracrine factors
Authors: Savneet Kaur, Dinesh Tripathi, Ketki Dongre, Vishal Garg, Sheetalnath Rooge, Asok Mukopadhyay, Puja Sakhuja, Shiv K. Sarin
Journal: Journal of Hepatology (2012)
Epicardial mapping and electrocardiographic models of myocardial ischemic injury.
Authors: G T Smith, G Geary, W Ruf, T H Roelofs, J J McNamara
Journal: Circulation (1979)

The amplitude and distribution of epicardial ST-segment elevation (ST) were examined for an 8-hour period after coronary occlusion in eight baboons and five pigs. ST was determined from unipolar epicardial electrograms obtained from a high-resolution matrix of fixed electrodes overlying a transmural region of ischemia. A relatively uniform degree of ST was observed overlying the ischemic region for 20 minutes after coronary occlusion. A gradient in ST from the periphery to the center of the ischemic region was documented after 20 minutes of ischemia. In 10 other pigs, change in the degree of ST was examined contingent on either an increase (five pigs) or decrease (five pigs) in the size of the ischemic region after 1 hour of preexisting ischemia. An abrupt increase in the number of electrodes that showed ST (NST) from 7.8 +/- 1.24 (SEM) to 14.8 +/- 1.35 (90%) was associated with an increase in mean ST of 58% from 4.28 +/- 0.61 mV to 6.78 +/- 0.84 (p less than 0.05). An abrupt decrease in NST from 25.2 +/- 2.63 to 14.6 +/- 2.22 (42%) was associated with a decrease in mean ST of 24%, from 8.2 +/- 0.36 mV to 6.3 +/- 0.30 mV (p less than 0.01). The results during early ischemia (less than 20 minutes of ischemia) are accurately represented by a model of ischemia in which injury current arises only at the ischemic boundary. The results during later ischemia (after 20 minutes of ischemia) may be represented by a model in which ST is considered dependent on injury currents generated throughout the ischemic region.
STUDIES ON THE SOMATIC C POLYSACCHARIDE OF PNEUMOCOCCUS
Authors: Theodore J. Abernethy
Journal: The Journal of Experimental Medicine (1937)

The capacity of the serum of rabbits following intradermal pneumococcus infections to precipitate in the presence of pneumococcus C polysaccharide has been studied during the resultant periods of active infection and during recovery. In rabbits infected with Type I, III, or VIII pneumococci, large hemorrhagic lesions are produced which frequently bring about death of the animals after a febrile illness of 3 to 4 days. Repeated precipitation tests with the sera of these animals have been uniformly and consistently negative, not only during the acute illness but in the recovery period as well. On the other hand, the sera of monkeys of the Macacus cynomolgos species actively ill with experimental Type III pneumonia have been shown to react in precipitation tests with the C substance. The serum reaction appears within the first 24 hours after infection, remains positive in high titer for 2 to 3 days during the acute illness, and disappears with the onset of recovery. The precipitation reaction with C also occurs with the sera of monkeys following intradermal and intraperitoneal infection with pneumococci. The results of precipitation tests of the serum of monkeys during experimental pneumonia are similar to those obtained with the sera of patients suffering from pneumococcus lobar pneumonia. From the results of these studies it would appear improbable that the demonstration of the serum precipitation phenomenon with C polysaccharide in monkeys, and possibly also in man, is conditioned by previous exposure to pneumococcus antigen.
Distribution of methyl sulfone metabolites of polychlorinated biphenyls and p,p'-DDE in human tissues.
Authors: Shaogang Chu, Adrian Covaci, Werner Jacobs, Koichi Haraguchi, Paul Schepens
Journal: Environmental Health Perspectives (2003)

We determined methylsulfonyl metabolites of chlorinated biphenyls (MeSO2-CBs) and 1,1-bis(4-chlorophenyl)-2,2-dichloroethene (p,p'-DDE) in human adipose, liver, brain, and lung tissues obtained from 11 Belgian individuals (9-62 years of age). The total concentration of MeSO2-CBs (lipid weight basis) decreased in the following order: liver (mean, 9.30 ng/g; range, 1.68-27.03 ng/g lipid) > lung [mean, 2.72 ng/g; range, not detected (ND) to 11.54 ng/g lipid] > adipose tissue (mean, 1.57 ng/g; range, 0.33-4.33 ng/g lipid) > brain (mean, 0.24 ng/g; range, ND-0.56 ng/g lipid). The profiles of MeSO2-CBs and MeSO2-DDE in each tissue were similar for all 11 subjects. In adipose, brain, and lung tissues, 4'-MeSO2-CB87, 4'-MeSO2-CB101, and 3-MeSO2-CB149 (except brain) occurred at higher concentrations than did other MeSO2-CBs. However, 3'-MeSO2-CB132 was by far the most abundant congener in liver, contributing on average to approximately 60% of the sum of MeSO2-CBs. The concentrations of 3-MeSO2-DDE in different tissues were at the same or lower levels than the total concentrations of MeSO2-CBs. This study suggests that the distribution patterns of MeSO2-CBs and MeSO2-DDE in humans differ between liver and other tissues. Moreover, these profiles differ from those found in other mammals, such as polar bears, porpoises, and otters.
Morphine and Papaveretum
Authors: W. B. Loan, R. S. J. Clarke, J. W. Dundee
Journal: BMJ (1970)

The evaluation of decisions in the multidisciplinary meeting (MDM) is a useful tool for the analysis of professional practices. We report our experience of doing a retrospective analysis of new cases of lung cancer presented in MDM from 2006 to 2011 with comparison between MDM and decisions support real patient. 962 records submitted on first line, there were 794 cases of lung cancer (88% men) mostly NSCLC: 88.2% (33.9% adenocarcinoma, squamous 41.6%), advanced stage (stage III 30.4%, stage IV 57%). At the first presentation of the case histology was present in 98% of cases, the T and N defined in all patients, TNM was complete in 50.8% of cases. Average of three weeks elapsed between the first imaging and histological evidence, then a week before the proposed therapeutic MDM, the average time between MDM and the treatment was variable (1 week in case of chemotherapy, 3 weeks if surgery, 15 weeks in case of radiotherapy). The compliance rate for surgical decision was 80% (non-compliance was due to disruption of functional assessment preoperative) chemotherapy for 82% (non-compliance due to a deterioration of the general condition and the patient9s refusal) and the treatment with chemoradiotherapy 49%. 100% compliance decisions investigations, surveillance or symptomatic treatment. The overall compliance rate was 77.7%, the implementation of decisions taken was faced with several challenges such as availability of antimitotic treatment the difficulty of access to some care.
Abstract 3387: Secreted exosomes from cultured bladder cells are enriched for distinct miRNAs detected in circulation of metastatic bladder cancer patients
Authors: Marie S. Ostenfeld, Dennis Jeppesen, Jens P. Morth, Huy B. Khanh, Dan Theodorescu, Michael Borre, Lars Dyrskjøt, Torben Ørntoft
Journal: Cancer Research (2012)

Abstract Exosomes are small nanovesicles (30-100 nm) secreted from the cell surface of most cell types. The vesicles are secreted at increased levels by cancer cells and can be detected in body fluids of cancer patients. Exosomes function in paracrine delivery of proteins, RNA, and DNA into recipient cells. By this, exosomes are speculated to be involved e.g. in pre-metastatic niche formation at distant sites. Here we present a characterization of exosome vesicles isolated from bladder cancer cells as examined by electron microscopy, dynamic light scattering and by western blotting of common exosome protein markers. The expression of 671 unique human miRNAs by qPCR was analyzed in both exosomes and donor cells from: 1) cultivated normal urothelial cells (NHU), 2) T24 bladder carcinoma cell line (non-metastatic) and its metastatic isogenic derivates FL3 and SLT4 and 3) UMUC3 bladder carcinoma cell line (moderate metastatic) and its highly metastatic isogenic derivative LUL2. Several miRNAs were detected in the vesicles yet absent in their parental donor cell indicating a possible preferential vesicular packaging. miRNAs miR92a, -106a, -20a, -21, -16, and let-7a/b/d/e were detected among the top100 ranked miRNAs in all vesicles. Among the top30 enriched exosomal miRNAs, miR-223 and-383 were detected in all cancer vesicles, and miR-921 in the highly metastatic vesicles (FL3, SLT4, LUL2). The release of miRNAs (miR-21, -16, and let7b) from FL3 cells into the culture media was time-dependent and a fraction of these miRNAs were stable to RNaseOne degradation indicating possible protection inside the vesicles. Examination of miRNAs in human plasma samples also suggested resistance towards endogenous RNAse degradation as well as towards repetitive freeze/thawing. The profiling of miRNA expression by Affymetrix microarray analysis of crude exosome-containing fractions of human plasma samples (10 healthy controls and 10 cases of metastatic bladder cancer) showed significant upregulation in cancer plasma of e.g. miR-92a, -106a, -23a, -20a, -21, some of which were the same as the miRNAs highly expressed in the tumor vesicles. The significant increase was confirmed by q-RT-PCR for miR-92a and -23a and validated on an independent set of plasma samples (8 healthy controls and 8 metastatic cancer cases). Our results suggest that specific miRNAs are encapsulated into exosomes in bladder cancer and that these may be detected in circulation in advanced stages of bladder cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3387. doi:1538-7445.AM2012-3387
Adenovirus-mediated HIF-1α gene transfer promotes repair of mouse airway allograft microvasculature and attenuates chronic rejection
Authors: Xinguo Jiang, Mohammad A. Khan, Wen Tian, Joshua Beilke, Ramesh Natarajan, Jon Kosek, Mervin C. Yoder, Gregg L. Semenza, Mark R. Nicolls
Journal: Journal of Clinical Investigation (2011)

Chronic rejection, manifested as small airway fibrosis (obliterative bronchiolitis [OB]), is the main obstacle to long-term survival in lung transplantation. Recent studies demonstrate that the airways involved in a lung transplant are relatively hypoxic at baseline and that OB pathogenesis may be linked to ischemia induced by a transient loss of airway microvasculature. Here, we show that HIF-1α mediates airway microvascular repair in a model of orthotopic tracheal transplantation. Grafts with a conditional knockout of Hif1a demonstrated diminished recruitment of recipient-derived Tie2⁺ angiogenic cells to the allograft, impaired repair of damaged microvasculature, accelerated loss of microvascular perfusion, and hastened denudation of epithelial cells. In contrast, graft HIF-1α overexpression induced via an adenoviral vector prolonged airway microvascular perfusion, preserved epithelial integrity, extended the time window for the graft to be rescued from chronic rejection, and attenuated airway fibrotic remodeling. HIF-1α overexpression induced the expression of proangiogenic factors such as Sdf1, Plgf, and Vegf, and promoted the recruitment of vasoreparative Tie2⁺ cells. This study demonstrates that a therapy that enhances vascular integrity during acute rejection may promote graft health and prevent chronic rejection.
Better ways of assessing health needs in primary care
Authors: J. Shanks, S. Kheraj, S. Fish
Journal: BMJ (1995)

Commissioning authorities increasingly attempt to base their purchasing decisions on systematic, epidemiologically informed assessment of the health needs of their local populations. General practitioners as purchasers usually rely on their own judgment. No one knows which method works better, but a combined approach may capture some of the advantages of both.

One of the more widely welcomed aspects of the NHS reforms was the requirement that health authorities' decisions on how to use NHS resources should in future be based on a systematic assessment of each local population's needs for health care. This is meant to take account of local demography, the epidemiology of health problems, evidence on the effectiveness of treatments, and the preferences of local people.1 Needs assessment has become an important task for public health doctors and others working in commissioning authorities. This more rational and scientific method is put forward as an improvement over the former approach to allocating health funding, caricatured as “same as last year, plus or minus five per cent for pressure groups.”2

The most obvious way in which general practitioners can shape decisions on the pattern of purchasing for hospital and community health services is by becoming fundholders. Non-fundholding general …
Nose-Drop Intoxication In an Infant
Authors: Richard E. Thompson
Journal: JAMA (1970)

To the Editor:—  Naphazoline (Privine) hydrochloride, tetrahydrozoline hydrochloride (Tyzine), oxymetazoline hydrochloride (Afrin), and xylometazoline (Otrivin) hydrochloride are potent vasoconstrictors used to relieve nasal stuffiness. The other major effect of these drugs is depression of the central nervous system.  Several years ago,LETTERS TO THE EDITORinThe Journalreminded physicians of possible harmful side effects of this class of drugs in infants and small children. 1,2 A recent experience with xylometazoline nose drops demonstrates the importance of keeping this warning in mind.  Report of a Case:—  A 1-month-old Negro male infant was seen in the pediatric clinic at Martin Army Hospital, Ft. Benning, Ga. The patient exhibited poor responsiveness and gasping respirations. He was rushed to the ward with the initial impression of meningitis, encephalitis, or severe pneumonia. Physical examination, laboratory studies including salicylate level and spinal fluid examination, and chest x-ray film failed to reveal any specific abnormality. The
Histological and angiographic effects of a pulsed holmium: YAG laser in normal and atherosclerotic human coronary arteries and aorta
Authors: C. R McKay, S. K Landas, P. S Hanson, D. Robertson, B. Waller, M. D Winniford
Journal: Cardiovascular Research (1992)

Objective: The aims were (1) To determine the histological and angiographic effects of holmium: YAG laser energy delivered through clinical multifibre laser catheters on fresh cadaveric coronary arteries; and (2) to relate the placement of optical fibres in the catheter to patterns of tissue ablation in cadaveric aorta. Methods: Eight fresh cadaveric hearts and segments of aorta were used. Hearts were mounted on a new pressure perfusion device. The laser catheter was delivered over a guidewire in the lumen until it met an area of resistance. The coronary artery lumen was perfused at approximately 100 mm Hg mean pressure. These arterial areas were identified on angiography, marked, and then exposed to laser energy in the range 600-3000 mJ·mm−2. Normal and atherosclerotic areas of fresh cadaveric aortic strips were exposed to increasing laser energies using either constant or increasing fluence. Coronary arteries were pressure perfused with formalin for 18-24 h at 100 mm Hg mean pressure, and aortic strips were immersed in 5% formalin. Light and scanning electron microscopy studies were carried out. Results: There were no perforations or dissections by angiography in the fresh coronary arteries. One of 15 normal coronary artery segments and 10 of 16 of the pressure perfused, fixed, atherosclerotic coronary artery segments showed thermal changes associated with atherosclerotic plaque ablation. In aortic tissue, thermal effects extended 0 to 0.6 mm lateral to the ablated crater. Acoustic effects were seen only in the aortic strips after ablation at fluences >1000 mJ·mm−2. The "dead spaces" around the optical fibres in the catheter resulted in significant amounts of coagulated tissue fragments remaining in the crater. Conclusions: Holmium:YAG laser energy delivered through multifibre catheters ablated atherosclerotic tissue in coronary arteries with minimal damage to the normal walls. The cadaveric coronary artery perfusion apparatus is useful for assessing catheter delivery and mobility and the effects of laser energy on the coaxially orientated normal and atherosclerotic coronary arterial wall. Cardiovascular Research 1992;26:994–1000
Abstract 1996: Molecular stratification of clear cell renal cell carcinoma by consensus clustering reveals distinct subtypes and survival patterns
Authors: A. Rose Brannon, Anupama Reddy, Michael Seiler, Alexandra Arreola, Shufen Chen, Dominic T. Moore, Raj S. Pruthi, Eric M. Wallen, Matthew E. Nielsen, Huiqing Liu, Börje Ljungberg, Hongjuan Zhao, James D. Brooks, Shridar Ganesan, Gyan Bhanot, W. Kimryn Rathmell
Journal: Cancer Research (2010)

Abstract Clear cell renal cell carcinoma (ccRCC) is the most prevalent form of kidney cancer and presents in the clinical setting with a heterogeneous and difficult to predict natural history. Previous research has suggested the existence of molecular subtypes of ccRCC, but these studies have failed to elucidate the pathways driving these subtypes or provide gene sets translatable to clinic. Given the common use of molecularly targeted therapies in the clinic, a better understanding of the underlying tumor biology would clearly augment treatment decisions. In this study, gene expression microarray data from 48 patients was analyzed with ConsensusCluster, software that uses unsupervised consensus clustering algorithms to identify the most optimal innate molecular subclasses. Without clinical or other classifying information, this analysis identified two distinct subtypes of ccRCC within the training set, labeled clear cell type A (ccA) and B (ccB). Based on the most well-defined arrays in each subtype, Logical Analysis of Data (LAD) defined a highly accurate set of 120 probes that could then be subsampled to classify additional tumors individually. The subclasses were substantiated in a validation dataset of 177 tumors and analyzed for clinical outcome, demonstrating that tumors designated ccA have markedly improved disease-specific survival compared to ccB (median survival of 8.6 vs. 2.0 years, p=0.002). When analyzed by both univariate and multivariate analysis, the classification schema independently associated with survival. Furthermore, gene set analysis of both datasets suggests that ccB tumors overexpress more immature and aggressive pathways, while ccA tumors overexpress classic ccRCC pathways of metabolism and angiogenesis. Therefore, using only patterns of gene expression, a small gene set was defined that classified ccRCC into two robust subclasses with distinct biological pathway expression and marked differences in clinical outcome. This classification schema, which is applicable to individual tumors, has implicit repercussions for influencing treatment decisions, defining biological mechanisms involved in ccRCC tumor progression, and directing future drug discovery. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1996.
SOME NON-MEDICINAL SUGGESTIONS IN THE THERAPEUTICS OF EPILEPSY.
Authors: S. J. FORT
Journal: JAMA (1895)

Interest in the manner of how not to give medicine in the treatment of disease is daily increasing, and there is, probably, no domain of morbid condition to which human nature has fallen heir that repays non-medicinal medicine more rapidly and well than the so-called diseases of the nervous system, and while epilepsy may perhaps not be a disease pure and simple, for convenience of discussion, it may still remain under that caption. It may be well to state also, that all medicine must not be condemned because in the past the stomachs of our forefathers or even nearer relations, perhaps those bearing the names which appear upon our own visiting lists, have been dosed<i>ad nauseam</i>with the long list of drugs in our pharmacopœia; this is no reason for throwing aside these valuable aids to nature's recovery; it is simply an argument for a more thorough diagnosis, a