tbuckley/cabot-search huggingface dataset:
Radiation: A Chemical
Authors: Sydney F. Thomas
Journal: JAMA (1961)

The mechanisms by which ionizing radiation ultimately produces a clinical result are very complicated, but a study of the process of polymerization offers a suitable approach. Polymerization can be initiated by very low doses of ionizing radiation. The random events occurring within chemicals, within cells, or within tissues after irradiation are the results of effects produced by the energy exchange at the randomly spaced sensitive areas, and the results can be both degradation and synthesis of polymeric matrices. This concept is proposed as an integrating complement to the chemical and target theories of radiation effects. It should also afford a logical basis for the methodical investigation of the place of chemicals in combination with irradiation in the treatment of tumors.
Assessment of Cardiac Function
Authors: Eugene Braunwald, John Ross, James H. Gault, Dean T. Mason, Christopher Mills, Ivor T. Gabe, Stephen E. Epstein
Journal: Annals of Internal Medicine (1969)

In the past, assessment of cardiac function has centered on techniques that examined the heart's action as a pump. Hemodynamic analysis of cardiac function within the framework of the Frank-Starling relation is valuable when directional changes in the performance under stress of the diseased ventricle are compared with the normal. Recently, principles of skeletal muscle physiology have been extended to the myocardium and applied successfully to examination of the function of the intact heart. Angiography in patients revealed that specific alterations in the pattern of contraction occur in patients with left ventricular disease, principally a decrease in extent and velocity of fiber shortening, associated with decrease in the extent of reduction of ventricular wall tension during contraction. Estimates of contractile state based on the tension-velocity-length relation determined angiographically sensitively quantify the myocardial contractile state in patients, even during abnormal ventricular loading. A second useful method for assessment of cardiac function in patients consists of relating the first derivative of the ventricular pressure to the simultaneously occurring isovolumic pressure. A third promising method measures pulmonary arterial and aortic blood flow velocity by a cathetertip velocity probe. This instrument uses the principle of the external electromagnetic flow meter; its potential applicability to assessment of myocardial function has been shown. Use of the cardiac output response to exercise in the assessment of cardiac function is reviewed. Measurement of the cardiac output when exercise has lowered the mixed venous oxygen saturation to 30% is useful, reliably and sensitively distinguishing performance of the patient with mild or moderate impairment of cardiac function from normal.
Domestic exposure to formaldehyde significantly increases the risk of asthma in young children
Authors: K.B. Rumchev, J.T. Spickett, M.K. Bulsara, M.R. Phillips, S.M. Stick
Journal: European Respiratory Journal (2002)

Concern has arisen in recent years about indoor air pollution as a risk factor for asthma. Formaldehyde exposure was examined in relation to asthma among young children (between 6 months and 3 yrs old) in a population-based control study carried out in Perth, Western Australia, between 1997–1999. An association between exposure to formaldehyde and asthma in young children has been suggested. Cases (n=88), whose parents were recruited at Princess Margaret Hospital Accident and Emergency Dept (Perth, Western Australia), were children discharged with asthma as the primary diagnosis. Controls (n=104), who were children in the same age group without asthma diagnosed by a doctor, were identified from birth records through the Health Dept of Western Australia (Perth, Western Australia). Health outcomes for the children were studied using a respiratory questionnaire and skin-prick tests. Formaldehyde, average temperature and relative humidity were measured on two occasions, winter (July–September 1998) and summer (December 1998–March 1999) in the child's bedroom and in the living room. The study found seasonal differences in formaldehyde levels in the children's bedrooms and living rooms with significantly greater formaldehyde exposure during the summer period for case and control subjects. The generalised estimating equation model showed that children exposed to formaldehyde levels of ≥60 µg·m −3 are at increased risk of having asthma. The results suggest that domestic exposure to formaldehyde increases the risk of childhood asthma.
Annular lesion of the lung in sarcoidosis.
Authors: H Tada, R Yasumizu, S Yuasa, M Sato, Y Mizuno
Journal: Thorax (1989)

A 20 year old man presented with eight thin walled, ring shaped shadows, 1-3 cm in diameter, on a chest radiograph. Pulmonary sarcoidosis was diagnosed on the basis of histopathological examination of a cervical lymph node, transbronchial lung biopsy, and increased activity of angiotensin converting enzyme and lysozyme in serum. The lesions disappeared within six months of his starting corticosteroid treatment.
Clinical and biochemical observations on three cases of hypoxanthine-guanine phosphoribosyltransferase deficiency.
Authors: D.N Bunn, I.K Moss, A Nicholls, J.T Scott, M.L Snaith, M.R Watson
Journal: Annals of the Rheumatic Diseases (1975)

Clinical and enzymatic studies on two brothers with severe deficiencies of erythrocyte hypoxanthineguanine phosphoribosyltransferase (HGPRTase) are described, and are compared with similar studies of a classical case of the Lesch-Nyhan syndrome from another family. The two brothers have no neurological abnormalities, only traces of erythrocyte HGPRTase, erythrocyte adenine phosphoribosyltransferase activities approaching the high levels found in the Lesch-Nyhan patient, and similarly raised plasma and urinary concentrations of uric acid. Despite these strong biochemical similarities between the three patients, there were wide differences in the clinical case histories. In both families the enzyme deficiency appeared to be inherited as an X-linked character through asymptomatic carrier females. The relationship of HGPRTase deficiencies to the Lesch-Nyhan syndrome is discussed. Some observations relating to techniques are reported. Cellulose acetate has been found to give much better separations of labelled reaction products in low-level phosphoribosyltransferase assays than filter paper, when used as a supporting medium for electrophoresis. The analysis of hair follicles gives indications of individuals heterozygous for the enzyme deficiency, but the proportion of enzyme-deficient follicles was very small, and the test needs support from studies of other cell types. Using haemolysates, there were signs of a slow indirect conversion of hypoxanthine to inosinic acid, via inosine. Inosine appears to be labelled by a ribosyl-transfer reaction.
PARP-1 Inhibition Increases Mitochondrial Metabolism through SIRT1 Activation
Authors: Péter Bai, Carles Cantó, Hugues Oudart, Attila Brunyánszki, Yana Cen, Charles Thomas, Hiroyasu Yamamoto, Aline Huber, Borbála Kiss, Riekelt H. Houtkooper, Kristina Schoonjans, Valérie Schreiber, Anthony A. Sauve, Josiane Menissier-de Murcia, Johan Auwerx
Journal: Cell Metabolism (2011)
Full automation in allergy testing: measurement of specific IgE by the ENEA System
Authors: M. Plebani, D. Faggian, F. Borghesan
Journal: Allergy (1995)

We evaluated the ENEA System, a fully automated instrument for the measurement of specific IgE antibodies. The instrument dispenses sera and reagents, incubates, washes, and reads and prints results automatically. The “core” of the instrument is the reactive unit called ACE (Allergy Chamber Enzymatic), which is a new solid phase to which the allergens are linked. The system uses calibration curves specific for the major allergen families, and data are supplied qualitatively (five classes) and quantitatively. We evaluated the analytic efficiency of the system and its correlation with the in vivo test (skin prick test (SPT)) results in 60 patients with inhalant allergic diseases and in 20 controls. Results: 450 results were available within 4 h. A satisfactory within‐run (CVs between 1.58 and 6.2%) and between‐run (CVs 6.3–11.5%) precision was found. No significant earn‐over was observed. A wide linearity of the assay was demonstrated. With the concordance between the clinical history and SPT as the reference value, the clinical sensitivity of the ENEA System was 84.1 %, the specificity 82.8%, and the overall efficiency 83.4%. Finally, a good agreement with the results of another technique for the in vitro measurement of specific IgE (Pharmacia CAP System) was proven.
Gene Expression Profile Identifies Tyrosine Kinase c-Met as a Targetable Mediator of Antiangiogenic Therapy Resistance
Authors: Arman Jahangiri, Michael De Lay, Liane M. Miller, W. Shawn Carbonell, Yu-Long Hu, Kan Lu, Maxwell W. Tom, Jesse Paquette, Taku A. Tokuyasu, Sean Tsao, Roxanne Marshall, Arie Perry, Kirsten M. Bjorgan, Myriam M. Chaumeil, Sabrina M. Ronen, Gabriele Bergers, Manish K. Aghi
Journal: Clinical Cancer Research (2013)

Abstract Purpose: To identify mediators of glioblastoma antiangiogenic therapy resistance and target these mediators in xenografts. Experimental Design: We conducted microarray analysis comparing bevacizumab-resistant glioblastomas (BRG) with pretreatment tumors from the same patients. We established novel xenograft models of antiangiogenic therapy resistance to target candidate resistance mediator(s). Results: BRG microarray analysis revealed upregulation versus pretreatment of receptor tyrosine kinase c-Met, which underwent further investigation because of its prior biologic plausibility as a bevacizumab resistance mediator. BRGs exhibited increased hypoxia versus pretreatment in a manner correlating with their c-Met upregulation, increased c-Met phosphorylation, and increased phosphorylation of c-Met–activated focal adhesion kinase and STAT3. We developed 2 novel xenograft models of antiangiogenic therapy resistance. In the first model, serial bevacizumab treatment of an initially responsive xenograft generated a xenograft with acquired bevacizumab resistance, which exhibited upregulated c-Met expression versus pretreatment. In the second model, a BRG-derived xenograft maintained refractoriness to the MRI tumor vasculature alterations and survival-promoting effects of bevacizumab. Growth of this BRG-derived xenograft was inhibited by a c-Met inhibitor. Transducing these xenograft cells with c-Met short hairpin RNA inhibited their invasion and survival in hypoxia, disrupted their mesenchymal morphology, and converted them from bevacizumab-resistant to bevacizumab-responsive. Engineering bevacizumab-responsive cells to express constitutively active c-Met caused these cells to form bevacizumab-resistant xenografts. Conclusion: These findings support the role of c-Met in survival in hypoxia and invasion, features associated with antiangiogenic therapy resistance, and growth and therapeutic resistance of xenografts resistant to antiangiogenic therapy. Therapeutically targeting c-Met could prevent or overcome antiangiogenic therapy resistance. Clin Cancer Res; 19(7); 1773–83. ©2012 AACR.
A molecular map of G protein alpha chains in microdissected rat nephron segments.
Authors: S I Senkfor, G L Johnson, T Berl
Journal: Journal of Clinical Investigation (1993)

Membrane-associated guanine nucleotide binding proteins regulate many receptor-mediated signals. Heterogeneity of biochemical and functional properties in nephron segments could be due to differences in G protein expression. To ascertain whether such heterogeneity of G proteins is present in various nephron segments, this study examines the distribution and relative abundance of G protein alpha chains in microdissected medullary thick ascending limb, cortical collecting tubules, outer medullary collecting tubules, proximal inner medullary tubules, and distal inner medullary tubules. Reverse transcription and polymerase chain reactions were employed using oligonucleotides encoding highly conserved regions of all known alpha chains. The cDNA was sequenced for alpha chain identification. The alpha i2 versus alpha s distribution was different in the outer medullary collecting tubules, when compared with the medullary thick ascending limb (P < 0.001) or the cortical collecting tubule, the proximal inner medullary tubules, and the distal inner medullary tubules (P < 0.05). These latter four segments did not significantly differ from each other. A similar analysis was applied to the frequently used line of kidney cells, LLC-PK1, whose exact cellular origin remains unclear. Interestingly, we detected both alpha i2 and alpha i3, while only alpha i2 was detected in the rat distal nephron. No alpha o or alpha z reverse transcription PCR products were detected. In contrast alpha 11 and alpha 14 members of the more recently described alpha q family were detected in the outer medullary collecting tubules and the proximal inner medullary tubules, respectively. We conclude that the majority of nephron segments have a relatively constant distribution of G protein alpha chains.
THE INSTANTANEOUS DIAGNOSIS OF ALKAPTONURIA ON A SINGLE DROP OF URINE
Authors: Ella H. Fishberg
Journal: JAMA (1942)

Alkaptonuria is a rare metabolic anomaly characterized by the tendency of the urine to turn dark on exposure to air, owing to the fact that the urine contains homogentisic acid. The constitution of this compound, which is chemically 1-4 dihydroxyphenylacetic acidshows that it may be regarded as a derivative of hydroquinone and points the way to its instant detection in urine. The urine is made strongly alkaline with sodium or potassium hydroxide and dropped on regulation sensitized photographic paper. Wherever a drop of the urine touches the paper the latter turns coal black instantly, a process exactly similar to that used in everyday photography. This may be done in full daylight. We have found no other substance present in urine, either normally or pathologically, which is capable of reducing the photographic paper in this manner. Diabetic urine, no matter how high the concentration of reducing sugar, remains without effect.
Interleukin-22, liver progenitor cells, and liver cancer
Authors: Dechun Feng
Journal: Hepatology (2013)

We read the discussion about interleukin (IL)-22 as a negative prognostic indicator in viral hepatitis-related hepatocellular carcinoma (HCC).1 It is clear that IL-22 is a hepatoprotective cytokine. A phase I clinical trial of IL-22 has been carried out (http://www.businesswire.com/news/home/20120906005611/en/Generon-Initiates-Phase-Clinical-Study-F-652-Australia). On the other hand, Radaeva et al. reported that IL-22 also promoted human HCC growth by activating signal transducer and activator of transcription 3 (STAT3) and subsequently up-regulating STAT3 target genes,2 which was confirmed by others.3 Recently, our group reported that IL-22 transgenic (Tg) mice developed more and larger liver tumor after diethylnitrosamine injection.4 Interestingly, IL-22 Tg mice did not spontaneously develop liver tumors. These findings suggest that IL-22 alone does not initiate liver tumors, but can promote hepatic carcinogenesis together with other risk factors. We recently demonstrated that IL-22 can also promote the growth of liver progenitor cells (LPCs), which partially explains the expansion of LPCs in chronic viral hepatitis patients resulting from higher IL-22 levels in these patients.5 LPCs are considered as an important source of liver cancer stem cells. To test whether IL-22-induced LPC expansion contributes to carcinogenesis, we fed wild type (WT) and IL-22 Tg mice with a 3,5-diethoxycarbonyl-1,4-dihydro-collidin diet for 7 months. Only 1 of 4 IL-22 Tg mice developed liver tumor, compared to 0 of 4 in WT mice. Although our study is preliminary, it suggests that additional factors are necessary for the transformation from LPCs to liver cancer stem cells (LCSCs). The hypothesis was supported by a study that found that increased tumorigenicity was discovered in LPCs with hepatitis B virus x protein expression.6 Taken together, elevated IL-22 can promote the growth of LPCs and HCC. However, in addition to IL-22, other factors, such as viral infection, are necessary for the transformation of LPCs to LCSCs and subsequent HCC initialization. Dechun Feng, Ph.D. Laboratory of Liver Diseases National Institute on Alcohol Abuse and Alcoholism National Institutes of Health Bethesda, MD
ARE WE HEADED FOR A DARK AGE OF NONDISCOVERY IN THERAPEUTICS?
Authors: Charles A. Ragan
Journal: JAMA (1967)

The pharmaceutical manufacturers have recently been having a bad time. Buffeted by hostile congressional committees, blown hither and yon by an increasingly aggressive but yet hesitant FDA, they have truly been placed in an unfavorable light, despite their excellent record of achievement. A large part of their profits has been put into research and development. As Congressman Melvin Laird (R, Wis) pointed out in a recent speech, in "an industry based on innovation, the pharmaceutical industry receives only 4% of its research and development money from the federal government, compared with 88% for aircraft and missiles and 55% for all manufacturing." Still, their drug prices are under constant attack and their marketing policies—particularly their advertising phraseology, which is carefully monitored—have been severely criticized. Comparing the advertising claims of the pharmaceutical industry with those of other industries—automotive, food, cosmetics—it obviously seems lily-white and low pressured. The whole battle over generic vs
Transcatheter and Ablative Therapeutic Approaches for Solid Malignancies
Authors: Eleni Liapi, Jean-Francois H. Geschwind
Journal: Journal of Clinical Oncology (2007)

The purpose of this article is to present in a concise manner an overview of the most widely used locoregional transcatheter and ablative therapies for solid malignancies. An extensive MEDLINE search was performed for this review. Therapies used for liver cancer were emphasized because these therapies are used most commonly in the liver. Applications in pulmonary, renal, and bone tumors were also discussed. These approaches were divided into catheter-based therapies (such as transcatheter arterial chemoembolization, bland embolization, and the most recent transcatheter arterial approach with drug-eluting microspheres), ablative therapies (such as chemical [ethanol or acetic acid injection]), and thermal ablative therapies (such as radiofrequency ablation, laser induced thermotherapy, microwave ablation, cryoablation, and extracorporeal high-intensity focused ultrasound ablation). A brief description of each technique and analysis of available data was reported for all therapies. Locoregional transcatheter and ablative therapies continue to be used mostly for palliation, but have also been used with curative intent. A growing body of evidence suggests clear survival benefit, excellent results regarding local tumor control, and improved quality of life. Clinical trials are underway to validate these results. Image-guided transcatheter and ablative approaches currently play an important role in the management of patients with various types of cancer-a role that is likely to grow even more given the technological advances in imaging, image-guidance systems, catheters, ablative tools, and drug delivery systems. As a result, the outcomes of patients with cancer undoubtedly will improve.
Intravenous Bolus Application of Streptokinase and of Anisoylated Plasminogen Streptokinase Activator Complex in Acute Myocardial Infarction
Authors: P. Hellstern, P. Doenecke, M. Köhler, H. Schwerdt, C. Özbek, C. Miyashita, L. Bette, E. Wenzel
Journal: Drugs (1987)
Intrathyroidal Parathyroid Adenoma: Preoperative Identification and Localization by Parathyroid Imaging
Authors: A R AL-SUHAILI, J LYNN, J P LAVENDER
Journal: Clinical Nuclear Medicine (1988)

The authors report, probably for the first time, a successful pre-operative localization of 7 mm intrathyroidal parathyroid adenoma which was successfully removed by using parathyroid imaging using a dual tracer (T1-201 and Tc- 99m) and subtraction technique.
Points from letters: Any future for graduate medical students?
Authors: K Foord
Journal: BMJ (1977)

Objective: To report a case of variegate porphyria (VP) who presented with severe hepatic dysfunction followed by acute sensorimotor axonal neuropathy. Background: Porphyrias are group of metabolic diseases caused by enzymes deficiency in heme biosynthetic pathway. VP is a rare type caused by protoporphyrinogen oxidase deficiency. The common manifestations are acute neurovisceral attacks and skin photosensitivity, but presentation with severe hepatic dysfunction is rare. Methods: Case analysis and literature review. Results: We report a 26-year-old woman who initially presented with abdominal pain, severe hyperbilirubinemia, elevated liver enzymes, and generalized edema for one month. Extensive workup for liver failure including blood test, imaging, liver biopsy, genetic testing failed to identify a cause. The patient was placed on transplant list. Later, she developed progressively generalized muscle weakness of hands and legs with tingling sensation within one week. Physical exam revealed moderate distal muscle weakness with impaired sensation, but no skin lesion. Nerve conduction study confirmed sensorimotor axonal polyneuropathy with predominant sensory involvement. Tests for common etiologic diagnosis of neuropathy were negative. Acute porphyria was one of differential diagnosis. Typical pattern of porphyric neuropathy is predominant motor neuropathy. Sensory predominant is uncommon presentation. The blood and urine tests suggested VP: negative urine delta-aminolevulinic acid, normal urine porphobilinogen (at two weeks), elevated total and subtotal plasma porphyrins, elevated urine coproporphyrin, and normal uroporphyrin. She received intravenous glucose for four days without improvement. After hemin administration and removal of hormonal intrauterine device, her liver function and motor power gradually improved, but paresthesia persisted for the following several months. Conclusions: Severe hepatic dysfunction without skin lesion is a rare manifestation of VP which makes the diagnosis challenging. Acute neuropathy, even with uncommon pattern, is a presentation that helps in diagnosis of this uncommon disease. Early administration of hemin and removal of precipitating triggers are essential treatment. <b>Disclosure:</b> Dr. Ruthirago has nothing to disclose. Dr. Julayanont has nothing to disclose. Dr. Tantikittichaikul has nothing to disclose. Dr. Kim has nothing to disclose.