tbuckley/cabot-search huggingface dataset:
Chlorpropamide-alcohol flushing and coronary heart disease in non-insulin dependent diabetics.
Authors: M Laakso, K Nuorva, A Aro, M Uusitupa, O Siitonen, R Huupponen
Journal: BMJ (1983)

magnesium concentrations may play a part in hyposecretion of parathyroid hormone, but our patient had consistently normal concentrations.Stress, in the form of serious underlying illness, may contribute to the development of hypoparathyroidism; our patient had a complex medical history.In retrospect she was found to have had a low serum calcium concentration before her first admission to hospital and may have had subclinical hypoparathyroidism then.We recommend that the serum calcium concentration be checked promptly in any elderly patient after an unexplained convulsion.We thank Dr B F Allam, consultant clinical biochemist at this hospital, for his invaluable help and guidance with this case.
Innovative Reporting of Penicillin Allergy in an Integrated Electronic Medical Record
Authors: P.J. Markus, D.M. Erickson, J.T.C. Li, R.R. Bessette, J.E. Rueter, D.R. Osmon, N.J. Larson, K.E. Kloos, M.A. Park
Journal: Journal of Allergy and Clinical Immunology (2007)
Effects of Inhaled Glucocorticoids on Bone Density in Premenopausal Women
Authors: Elliot Israel, Taruna R. Banerjee, Garrett M. Fitzmaurice, Tania V. Kotlov, Karen LaHive, Meryl S. LeBoff
Journal: New England Journal of Medicine (2001)

Inhaled glucocorticoids are the most commonly used medications for the long-term treatment of patients with asthma. Whether long-term therapy with inhaled glucocorticoids reduces bone mass, as oral glucocorticoid therapy does, is controversial. In a three-year prospective study, we examined the relation between the dose of inhaled glucocorticoids and the rate of bone loss in premenopausal women with asthma.
The Immunohistochemical Expression of Islet 1 and PAX8 by Rectal Neuroendocrine Tumors Should Be Taken into Account in the Differential Diagnosis of Metastatic Neuroendocrine Tumors of Unknown Primary Origin
Authors: Jamie Koo, Xiaoyan Zhou, Elizabeth Moschiano, Mariza De Peralta-Venturina, Richard B. Mertens, Deepti Dhall
Journal: Endocrine Pathology (2013)
Response of the A-V Node of the Rabbit to Stimulation of Intracardiac Cholinergic Nerves
Authors: THEODORE C. WEST, NOBORU TODA
Journal: Circulation Research (1967)

The cholinergic innervation of the rabbit heart was studied in vitro and in vivo. An isolated preparation, which included the combined atria, S-A node, A-V node and bundle of His, was mounted so that microelectrodes could be placed in either the specialized or nonspecialized tissues. Using a roving monopolar electrode, local transmural electrical stimulation of intracardiac nerves (nerve stimulation) was applied at the A-V or the S-A node. At the A-V node it induced hyperpolarization, reduced the duration and amplitude of action potentials recorded from three regions of the A-V node and the His bundle, whether the preparation was spontaneously beating or electrically driven in either the forward or retrograde direction, and blocked membrane excitation in the nodal and nodal-His regions and to downstream structures. The depressant effects of nerve stimulation were augmented by physostigmine and antagonized by atropine. Addition of acetylcholine to the bath reduced the frequency at which the A-V node conducted, but in the concentrations used did not duplicate the effects of nerve stimulation. The behavior of the S-A node is qualitatively similar to that of the A-V node. In the presence of a sinus rhythm, nerve stimulation applied at the A-V node did not affect the activity of the S-A node, and during artificial atrial drive, nerve stimulation of the S-A node did not affect A-V nodal function, indicating that little or no neural communication exists between the two regions in the isolated preparation. Locally released acetylcholine appears to depress excitability of specialized cells in the central node, independently of the direction of propagation.
Role of Third Serum Vitamin B12 Binding Protein in Vitamin B12 Transport
Authors: I. Chanarin, J. M. England, K. L. Rowe, J. A. Stacey
Journal: BMJ (1972)

A third vitamin B(12) binding protein present in normal serum has been shown to participate in transport of labelled vitamin B(12) absorbed from the gut. All three vitamin B(12) binding proteins in serum were labelled at the same time after oral administration of vitamin B(12), implying that "free" vitamin B(12) reached the portal blood from the gut mucosa.
THE NATURE AND SIGNIFICANCE OF CHANGES IN ADRENAL CYTOLOGY, WEIGHT, AND CORTICAL/MEDULLARY RATIO IN EXPERIMENTAL RENAL HYPERTENSION AND CLINICAL HYPERTENSION
Authors: L. J. Rather
Journal: The Journal of Experimental Medicine (1951)

There is a direct proportionality between the degree of adrenal and that of cardiac enlargement in experimental renal hypertension. This is evidence for the participation of the adrenal to an extent dependent on the severity of the hypertension as reflected in the degree of cardiac hypertrophy. The greater part of the weight increase of the adrenal is due to growth of the cortex. However, the relative degree of medullary growth exceeds that of cortical growth. There is evidence of medullary hyperplasia, but the cortical growth may be due to cell hypertrophy alone. In view of the known relationship between prolonged skeletal muscle work and the size of the adrenals, in which there is likewise a relatively greater growth of the medulla, the possibility that adrenal growth in experimental renal hypertension is a consequence of the metabolic demand of increased heart muscle work must be considered. The hyperplastic, hypertrophic medulla of the renal hypertensive rat is presumed to be producing increased amounts of a hormone whose action is not known. The adrenal medulla is not necessary for the development of moderate renal hypertension though this does not exclude the possibility that it may be involved somehow in the maintainance of the hypertensive state. Large, periodic-Schiff-positive, hyaline droplets are found in the cytoplasm of adrenal cortical cells with nuclear evidence of active function. There is some evidence that these indicate hypophyseal stimulation. Similar particles are found in the medulla, suggesting an interrelationship between the two parts of the adrenal. The close resemblance of changes in adrenal weight, nuclear/cytoplasmic ratio, and nuclear and cytoplasmic structure, indicates that similar physiological and morphological controlling mechanisms are involved in the pathogenesis and maintainance of experimental renal hypertension and clinical essential hypertension.
Vaginal speculum examinations without stirrups
Authors: Wendy Brooks Barr
Journal: BMJ (2006)

diabetes-as well as on opportunistic screening for early case finding.Ideally, public health measures are needed to prevent the onset of type 2 diabetes, especially among younger women. 1 8 This will be challenging in countries where the prevalence of type 2 diabetes is much higher than in the United Kingdom, and where there is limited access to pre-pregnancy and pregnancy care.
Abstract 2287: Nuclear localization of N-myc downstream regulated gene 4: A novel therapeutic target in meningioma
Authors: Rama P. Kotipatruni, Xuan Ren, Robert P. Vanderwaal, Dinesh Thotala, Jerry J. Jaboin
Journal: Cancer Research (2014)

Abstract NDRG4 is a member of the N-Myc downregulated gene family (NDRG) belonging to the alpha/beta hydrolase super family. The roles of NDRG4 in meningioma tumor development have not previously been evaluated. Effective local therapies include surgery and radiation, but there is a need for novel molecular targets to improve survival and reduce morbidity for meningioma patients. We have recently identified the N-Myc down regulated gene 4, NDRG4, protein as being overexpressed in aggressive meningiomas and demonstrated that NDRG4 downregulation results in decreased cell viability, migration and invasive properties. NDRG4 was initially identified as a cytoplasmic protein. In the present study, we proposed that nuclear localization of NDRG4 and the role of NDRG4 in cell proliferation. Subcellular distribution of NDRG4 was identified by western blotting in nuclear and cytosolic extracts. Immunocytofluoresence analysis revealed the NDRG4 nuclear localization. Here we demonstrate that depletion of NDRG4 induces the predominant form of cell death is apoptosis, utilizing DNA laddering and Annexin V/APC flow cytometry assay. We show that apoptosis caused by transduction of lentiviral shNDRG4 involves of p53 phoshorylation at ser 15, Bax activation. Flow cytometry analysis revealed changes in mitochondrial membrane potential (Ψm), which was observed by JC-1. Sub-cellular distribution of Bax and Cytochrome c indicated the mitochondrial-mediated apoptosis. In conclusion, we show that NDRG4 is also a nuclear protein expressed in response to cell proliferation and demonstrated the suppression of NDRG4 induces the apoptosis through p53 and Bax mediated intrinsic apoptotic pathway. Citation Format: Rama P. Kotipatruni, Xuan Ren, Robert P. Vanderwaal, Dinesh Thotala, Jerry J. Jaboin. Nuclear localization of N-myc downstream regulated gene 4: A novel therapeutic target in meningioma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2287. doi:10.1158/1538-7445.AM2014-2287
Aspirin and NS-398 inhibit hepatocyte growth factor-induced invasiveness of human hepatoma cells
Authors: Seigou Abiru, Kazuhiko Nakao, Tatsuki Ichikawa, Kiyoshi Migita, Masaya Shigeno, Miyuki Sakamoto, Hiroki Ishikawa, Keisuke Hamasaki, Keisuke Nakata, Katsumi Eguchi
Journal: Hepatology (2002)

Nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit cyclooxygenase (COX) activity and are considered to exert antitumor actions in a variety of cancer cells, although the effects are unlikely entirely due to COX inhibition. Because clinical observations suggest that hepatocyte growth factor (HGF) can promote metastasis of hepatoma cells while stimulating tumor invasiveness, we investigated the effect of aspirin and NS-398, a selective COX-2 inhibitor, on HGF-mediated invasiveness of HepG2 human hepatoma cells. HGF stimulated the invasiveness of HepG2 cells in Matrigel cell invasion assay, together with increased expression of matrix metalloproteinase (MMP) 9. Addition of aspirin or NS-398, similar to PD98059, which acts as a specific inhibitor of mitogen-activated protein kinase/extracellular signal-regulated kinase (MEK), an upstream kinase regulating extracellular signal-regulated kinase (ERK)1/2, abrogated such actions of HGF without affecting cell viability. Aspirin and NS-398, in contrast to PD98059, did not suppress ERK1/2 phosphorylation induced by HGF. However, both agents inhibited the kinase activity of ERK1/2 induced by HGF and repressed HGF-induced phosphorylation of 90-kd ribosomal S6 kinase (RSK) and Elk-1, key downstream substrates of ERK1/2, resulting in the suppression of transcriptional activity of Elk-1 as well as nuclear factor κB (NF-κB) and AP-1, which are involved in MMP-9 gene regulation. In conclusion, our results suggest that aspirin and NS-398 inhibit HGF-induced invasiveness of HepG2 human hepatoma cells through ERK1/2.
Abstract 4488: INK128: An orally active TORC1/2 kinase inhibitor demonstrates potent antitumor activity in preclinical models of renal cell carcinoma
Authors: Shunyou Wang, Linda Kessler, Jeff Kucharski, Lucy Lan, Xin Guo, Jocelyn Staunton, Marikka Elia, Josh Stewart, Jolene Brown, Liansheng Li, Katrina Chan, Mike Martin, Pingda Ren, Katti Jessen, Christian Rommel, Yi Liu
Journal: Cancer Research (2010)

Abstract Anti-angiogenic agents have demonstrated promising activity in patients with renal cell carcinoma (RCC). Patients with clear cell RCC often have mutations or silencing of the von Hippel-Lindau gene, leading to an accumulation of HIF 1 alpha (HIF1α), a key mediator of hypoxia-triggered neo-angiogenesis. The mammalian target of rapamycin (mTOR) is upstream of HIF1a and downstream of the VEGF pathway. mTOR kinase comprises two distinct multi-protein complexes, TORC1 and TORC2, which together regulate growth, metabolism, angiogenesis and survival. Pharmaceutical derivatives of rapamycin, a partial allosteric inhibitor of TORC1, provide clinical proof of concept for targeting mTOR in RCC as well as insights into how ATP-competitive TORC1/2 inhibitors might provide superior efficacy. Through rational drug design we have discovered INK128, a potent, selective TORC1/2 inhibitor with outstanding drug-like properties. We investigated INK128 in preclinical in vitro and in vivo models of RCC. Interestingly, while both INK128 and rapamycin exhibit comparable anti-angiogenic activity in vitro, INK128 correlated with potent and complete blockade of cell proliferation, while rapamycin failed to establish a dose-dependent maximum inhibition of tumor cell proliferation. A comparison of INK128, rapamycin, Nexavar and Avastin demonstrated that all exhibited potent inhibition of tumor growth, via different molecular mechanisms. INK128 inhibits phosphorylation of AKT, S6 and 4EBP1; rapamycin inhibits only S6 phosphorylation and induces AKT phosphorylation; Nexavar and Avastin have little effect on the PI3K/AKT/mTOR pathway. Only INK128 induced autophagy and decreased expression of cyclin D1. INK128 and rapamycin both inhibit expression of HIF-1α and VEGF, which contributes to their anti-angiogenic activity. We conclude that, although Nexavar, Avastin and rapamycin exert their activity primarily through effects on the tumor microenvironment, the anti-tumor activity of INK128 is derived from direct inhibition of tumor cell growth as well as anti-angiogenic activities. In summary, targeting TORC1/2 signaling with INK128 offers a compelling approach to the treatment of RCC. 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 4488.
Expression of transporters associated with antigen processing and human leucocyte antigen class I in malignant melanoma and its association with prognostic factors
Authors: J. Tao, Y. Li, Y-Q. Liu, L. Li, J. Liu, X. Shen, G-X. Shen, Y-T. Tu
Journal: British Journal of Dermatology (2007)

Background Low expression of transporters associated with antigen processing (TAP) and human leucocyte antigen (HLA) class I, due to defects in the antigen presentation pathway, is frequently found in human tumours, including malignant melanoma (MM). This immune evasion renders many tumours unrecognizable by the host immune surveillance system and appears to play a role in the clinical course of the tumour, probably because it provides tumour cells with a mechanism to escape cytotoxic T-lymphocyte recognition and destruction. However, the histopathological significance of TAP and HLA class I antigen defects in MM remains unclear. Objective To study the expression of TAP and HLA class I antigen in MM and the relationship between them. To investigate the correlation between histopathological characteristics and expression of these molecules in MM. Methods Tissue sections from 77 patients with MM and 20 with naevi were examined using immunohistochemistry and morphological quantitative analysis for protein expression of TAP1, TAP2 and HLA class I antigen. Results Positive TAP1, TAP2 and HLA class I antigen immunostaining was observed in 23%, 12% and 64% of MM lesions, respectively, and the expression of HLA class I was positively correlated with that of TAP1 and TAP2. However, expression of these molecules was positive in all of the pigmented naevi lesions. Reduced TAP1 and TAP2 protein expression in melanoma lesions was significantly associated with invasive growth, Clark's level and tumour-infiltrating lymphocytes. Reduced HLA class I antigen protein expression was only associated with tumour-infiltrating lymphocytes. Conclusions Our data suggest that reduced TAP1, TAP2 and HLA class I antigen protein expression in MM may contribute to the immune escape phenotype of human melanoma cells, and the main cause of reduced HLA class I expression may be the decreased TAP1 and TAP2 levels.
E3 Ligase Nedd4 Promotes Axon Branching by Downregulating PTEN
Authors: Jovana Drinjakovic, Hosung Jung, Douglas S. Campbell, Laure Strochlic, Asha Dwivedy, Christine E. Holt
Journal: Neuron (2010)

Regulated protein degradation via the ubiquitin-proteasome system (UPS) plays a central role in building synaptic connections, yet little is known about either which specific UPS components are involved or UPS targets in neurons. We report that inhibiting the UPS in developing Xenopus retinal ganglion cells (RGCs) with a dominant-negative ubiquitin mutant decreases terminal branching in the tectum but does not affect long-range navigation to the tectum. We identify Nedd4 as a prominently expressed E3 ligase in RGC axon growth cones and show that disrupting its function severely inhibits terminal branching. We further demonstrate that PTEN, a negative regulator of the PI3K pathway, is a key downstream target of Nedd4: not only does Nedd4 regulate PTEN levels in RGC growth cones, but also, the decrease of PTEN rescues the branching defect caused by Nedd4 inhibition. Together our data suggest that Nedd4-regulated PTEN is a key regulator of terminal arborization in vivo.
Trends in Pulmonary Function in Patients with Cystic Fibrosis Correlate with the Degree of Glucose Intolerance at Baseline
Authors: CARLOS E. MILLA, WARREN J. WARWICK, ANTOINETTE MORAN
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

In patients with cystic fibrosis, CF-related diabetes mellitus (CFRD) has been associated with increased morbidity and mortality. Whether glucose intolerance is also associated with poor outcomes is unclear. To better define these relationships we prospectively followed a group of 152 patients with CF without diabetes for 4 yr. Patients were classified as having normal glucose tolerance (NGT), impaired glucose tolerance (IGT), or CFRD without fasting hyperglycemia (CFRD-No FH). FEV1, FVC, and body mass index (BMI) were measured at baseline and quarterly. At baseline 45% of the patients had NGT, 38.8% had IGT, and 15.8% had CFRD-No FH. FEV1, FVC, and BMI at baseline were comparable among these groups (all p > 0.1). After 4 yr an overall decline in FEV1 and FVC occurred, with no change in BMI. The rates of decline for FEV1 and FVC correlated with the glucose tolerance groups, with the highest rates of decline occurring among the CFRD-No FH group. In addition, patients in the lowest quartile for insulin production at baseline experienced the highest rates of pulmonary function decline over time, suggesting a relationship between insulin deficiency and clinical deterioration. We conclude that the degree of glucose intolerance is a strong determinant of future lung function decline in patients with CF.
THE THERAPEUTIC USES OF THE THYMUS GLAND.
Authors: SOLOMON SOLIS-COHEN
Journal: JAMA (1900)

<h3>Mr. President and Gentlemen:</h3> —It is always a pleasure to meet my colleagues of the New York County Medical Association. I only regret that what I have to offer for your consideration is not very satisfactory. If at the close of my remarks you shall think that they have been vague and inconclusive, even contradictory, I shall have left on your minds a truthful picture of the state of our knowledge concerning the subject on which you have honored me by asking me to address you. It has long been known that children are liable to sudden death, attributed in some mysterious way to enlargement of the thymus gland. Authors have written learnedly on the subject, explaining, or rather failing to explain, these cases. In his classic study on diseases of the thymus gland, your honored fellow-townsman, Dr. A. Jacobi,<sup>1</sup>points out how a slight increase in bulk of
THE CORRELATION OF THE OVARIAN AND UTERINE FUNCTIONS
Authors: E. S. Carmichael, F. H. A. Marshall
Journal: BMJ (1907)

OVARIAN AND UTERINE FUNCTIONS.[ f°t. 30,i.}9. the peritoneum which had covered the tumour.It was obvious thatthe new disposition of the parts would cause a dangerous tractign,on the adherent coils of gut, and that a gradual shrinking of the growth must have had the same effect.I therefore separated the adherent coils, and found that the vermiform appendix was completely hidden by them.There was no sign ot a recent inflammation, but there was a round blaQk conoretion,-measuring about -i in. in diameter, within the appandix, close to its junction with -the caecum, and the adhesions were evidently due to an old appendicitis.All the small Intestine was released, and the appendix, which had reeq4ved much of its blood supply through the severed ad-hesions, was removed. After-HistojrysAfter the operation the patient gave no real occasion for anxiety during the first.week of convalescenee, although the bowels caused some discomfort and there was still a trace of albumen in the urine.On the eighth day the patient was so well and the -wound-appeared so firmly healed that, contrary to, my usual practe, 1 removed.all the sutures.During the
Predictive Value of Ventricular Arrhythmia Inducibility for Subsequent Ventricular Tachycardia or Ventricular Fibrillation in Multicenter Automatic Defibrillator Implantation Trial (MADIT) II Patients
Authors: James P. Daubert, Wojciech Zareba, W. Jackson Hall, Claudio Schuger, Andrew Corsello, Angel R. Leon, Mark L. Andrews, Scott McNitt, David T. Huang, Arthur J. Moss
Journal: Journal of the American College of Cardiology (2005)
Detection by polymerase chain reaction, cloning and sequencing of hepatitis delta virus (HDV)-RNA from the liver of a patient with a rapidly progressive HDV disease
Authors: S. Oliviero, L. D'Adamio, A. Smedile, E. Chiaberge, M.R. Brunetto, A. Ottabrelli, M. De Marchi, F. Banino
Journal: Journal of Hepatology (1989)
Diffusion and Binding of Monoclonal Antibody TNT-1 in Multicellular Tumor Spheroids
Authors: F.-M. Chen, E. B. Hansen, C. R. Taylor, A. L. Epstein
Journal: JNCI Journal of the National Cancer Institute (1991)

Tumor spheroids of HT-29 human colon adenocarcinoma and A375 melanoma were established to investigate the uptake and clearance kinetics of TNT-1, a monoclonal antibody that targets necrotic cells of tumors. Our data reveal that there was rapid uptake of TNT-1 and its F(ab')2 fragment in both spheroid models, whereas an antibody of irrelevant specificity, Lym-1, and its F(ab')2 fragment bound poorly to the spheroids. Unlike previously reported monoclonal antibodies to tumor cell-surface antigens, TNT-1 showed 1) a linear uptake that increased over time without saturation in tumor spheroids and 2) an unexpected uptake by a subpopulation of cells in the viable outer rim of the spheroids. These preclinical studies provide important information concerning the therapeutic potential of TNT monoclonal antibodies for the treatment of cancer and micrometastases.