tbuckley/cabot-search huggingface dataset:
Facts and Figures in Connection with the Climate of California
Authors: J. H. Parkinson
Journal: BMJ (1888)

suffered from gout in 'the feet for about four years.In that year he took 'for four weeks the 'strongest 'sutlphur 'water and baths.The following season (1886) he returned, having had two very slight attacks of gout during the spring.The general coidition was, however, changed for the worse.He was anaemic and languid; -the urine was very albuminous, although the skin still acted freely.After a few days of sulphur treatment the chalybeate was resorted to with benefit.The next year (1887) he reported' himself as moderately well, but he had had several gouty attacks in the feet and knees.One of these had been " brought on by a course of steel."The effervescing chalybeate was taken for three weeks, and he left the spa wlthout gouty symptoms, and much better in every respect, and able to walk several miles at a stretch.The urine remained faintly albuminous.It is thus evident that a sparkling iron water of moderate strength (a third of a grain to the pint) may be useful in gouty cases; or, rather, it may be groper to disregard the gout and treat in this manner the more serious maladies to which it has given rise.But whether gouty or otherwise, a condition exists of pre- mature senility of the tissues, with anemia (perhaps hydraemia), and often with signs of renal failure, in which carbonate of iron, freely diluted, is beneficial.And thus if.Leamington, with its saline chalybeate, is excellent in the ancemia of the young, so no less Strathpeffer, with its effervescing carbonated chalybeate, may be regarded as congenial to the anaemia with debility of the aged.Group II.-Dyspepsia in middle life, due to nervous prostration or overwork.CASE iv.-A lady of nearly 60, after severe domestic trial, began to complain of " rheumatic " pains, indigestion, and loss of strength and colour.She was recommended spinal douches and the chalybeate water, taken hot at noon.The quantity was soon increased to about forty ounces daily, divided into small doses.After a fortnight she left the spa, not without much improve- ment in health.In this class of cases the peculiarly stimulating effect of effervescing waters is often noticed, exhilaration and even giddiness following their use by delicate stomachs.Group III.-Chronic malarial affections.CASE v.-A lady, aged about 45, after much mental strain and bodily illness (dysentery and " fevers ") in tropical South America, returned home in ailing health, subject to recurring "internal chills," diarrhcea, and general weakness.She was stout, very anEemic, nervous, with frequent indigestion, headaches, and flying pains.For nearly four weeks this lady took the chalybeate, usually hot, and latterly to the extent of forty-five ounces daily.With this were combined occasional douches, sulphur baths, and massage, which no doubt contributed to a striking improvement in nervous, muscular, and digestive tone.For cases of this kind a very prolonged use of the water is to be recommended, repeated
Postischaemic hypercontraction is enhanced in ischaemically injured canine myocardium
Authors: T. Yoshikawa, M. Akaishi, F. Ikeda, S. Handa, Y. Nakamura
Journal: Cardiovascular Research (1992)

The aim was to identify the role of calcium flux in the pathogenesis of transient overshoot of regional myocardial contraction after brief ischaemia, ie, postischaemic hypercontraction.Ten anaesthetised mongrel dogs were examined under open chest conditions. The left anterior descending coronary artery was initially occluded for 2 min and reperfused for 10 min. A further period of coronary occlusion of 15 min duration was followed by 15 min reperfusion to produce postischaemic regional dysfunction. A third occlusion of 2 min duration was followed by 10 min reperfusion to induce postischaemic hypercontraction. Coronary blood flow was measured using an ultrasonic transit time flow meter. Segment length was measured by ultrasonic microcrystals.Postischaemic hypercontraction after 2 min coronary occlusion was exaggerated in ischaemically injured myocardium. The 10 dogs were divided into two groups, a control group (n = 5) and a verapamil treated group (n = 5), and were exposed to a final 2 min period of coronary occlusion with or without verapamil in the ischaemically injured myocardium. Postischaemic hypercontraction was attenuated in the verapamil treated group compared with the control group.Exaggeration of postischaemic hypercontraction in ischaemically injured myocardium may be mediated by a trans-sarcolemmal calcium flux. Changes in calcium flux may play a role in the pathogenesis of this phenomenon in the normal myocardium.
Human cord blood-derived mast cells adhere to extracellular matrix proteins by functional α4β1 (CD49d/CD29), α5β1 (CD49e/CD29), α4β7 integrins and CD44
Authors: Ilaria Puxeddu, Adrian M Piliponsky, Maroeska Oudshoorn, David Naor, Francesca Levi-Schaffer
Journal: Journal of Allergy and Clinical Immunology (2002)
Abstract A35: Aligned collagen is a prognostic signature for survival in human breast carcinoma
Authors: Matthew W. Conklin, Jens Eickhoff, Kristin Riching, Carolyn Pehlke, Kevin Eliceiri, Paolo Provenzano, Andreas Friedl, Patricia J. Keely
Journal: Cancer Research (2013)

Abstract Evidence for the potent influence of stromal organization and function on invasion and metastasis of breast tumors is ever growing. Here we have performed a rigorous examination of the relationship of a tumor-associated collagen signature (TACS-3), to the long term survival rate of human patients diagnosed with invasive breast cancer. TACS-3 is characterized by bundles of straightened and aligned collagen fibers that are oriented perpendicular to the tumor boundary. An evaluation of TACS-3 was performed in biopsied tissue sections from 196 patients by second harmonic generation (SHG) imaging of the backscattered signal generated by collagen. Univariate analysis of a Cox proportional hazard model demonstrated that the presence of TACS-3 was associated with poor disease-specific and disease free survival, resulting in hazard ratios between 3.0-3.9. Furthermore, TACS-3 was confirmed to be an independent prognostic indicator regardless of tumor grade and size, ER or PR status, HER-2 status, node status, and tumor subtype. Interestingly, TACS-3 was positively correlated to expression of stromal syndecan-1, a receptor for several extracellular matrix proteins including collagens. Ongoing research is currently investigating both the biochemical signaling pathways that give rise to the TACS-3 phenotype as well as the extent of the influence the mechanical properties of an aligned matrix have on invasion. Because of the strong statistical evidence for poor survival in patients with TACS, and since the assessment can be performed in routine histopathologic samples imaged via SHG or using picrosirius, we propose that quantifying collagen alignment is a viable, novel paradigm for the prediction of human breast cancer survival. Citation Format: Matthew W. Conklin, Jens Eickhoff, Kristin Riching, Carolyn Pehlke, Kevin Eliceiri, Paolo Provenzano, Andreas Friedl, Patricia J. Keely. Aligned collagen is a prognostic signature for survival in human breast carcinoma. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Invasion and Metastasis; Jan 20-23, 2013; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2013;73(3 Suppl):Abstract nr A35.
Abstract 3582: Targeting the FAK amino terminus F2 subdomain to disrupt growth factor receptor protein interactions, signaling and function
Authors: Deniz A. Ucar, Andrew Magis, Di-Hua He, David Ostrov, Steven N. Hochwald
Journal: Cancer Research (2011)

Abstract Introduction: Focal adhesion kinase (FAK), IGF-1R and the c-MET are tyrosine kinases that induce cell proliferation, invasion, metastases and survival. We have previously shown that FAK physically interacts with growth factor receptors in pancreatic cancer cells and is involved in tumor progression. Since IGF-1R and c-MET have significant structural similarity, we hypothesize that both interact with a similar conserved amino acid “patch” on FAK. We also hypothesize that this patch can be targeted with small molecules to inhibit pancreatic cancer essential signaling pathways and induce apoptosis. Methods: Based on Lipinski rules, we screened a chemical library of 240,000 compounds against a conserved patch on the F2 subdomain of FAK using in silico high throughput screening. We obtained the top scoring compounds from the National Cancer Institute Developmental Therapeutics Program and evaluated their effects on: 1) FAK protein interactions with c-MET and IGF-1R, 2) FAK, IGF-1R and c-MET kinase activity, 3)cell viability and apoptosis, and 4) growth of Panc-1 and Miapaca-2 pancreatic cancer cells in both orthotopic and direct xenograft mouse tumor models. Results: Based on co-immunoprecipitation assays, our lead compound blocked the interaction of FAK with both c-MET and IGF-1R in pancreatic cancer cells, without altering their kinase activity. Treatment with our lead compound led to decreased phosphorylation of AKT, inhibited cell viability and induced apoptosis in a dose-dependent manner (range 2-20μM). In addition, the combination of our lead compound with either 5-FU or gemcitabine chemotherapy resulted in a synergistic decrease in pancreatic cancer cell viability. More importantly, 10mg/kg of lead compound via subcutaneous injection, effectively (p&amp;lt;0.05) caused pancreatic tumor regression in vivo in both an orthotopic and direct xenograft model of pancreatic cancer. Conclusions: Our data suggest that targeting the protein interactions of FAK with growth factor receptors including c-MET and IGF-1R has specific therapeutic effects that can increase the sensitivity of pancreatic cancer cells to conventional chemotherapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3582. doi:10.1158/1538-7445.AM2011-3582
DIFFERENTIAL DIAGNOSIS BETWEEN GASTRIC AND DUODENAL ULCER AND GALLSTONES
Authors: WILLIAM D. HAGGARD
Journal: JAMA (1927)

Ulcer of the stomach and duodenum, if attended with typical symptoms of pain, vomiting and hemorrhage of ascertainable degree and accuracy of occurrence, is a very definite and easy diagnosis. An outspoken attack of severe biliary colic, so characteristic of gallstones, is not to be confused with any other lesion, as the condition is so dramatic and the symptoms so compelling that there is little room for doubt. Compared to the total number of cases of both diseases, the textbook symptoms are comparatively rare. The great majority of gastric and duodenal ulcers, as well as the multitudinous cases of gallstones and its associated lesions, are not easy of detection. Many times the symptoms are overlapping and confusing. The language of disease, when its diction, intonation and phraseology are perfect, is easily understandable. Unfortunately, it is often whispered and many times in an alien tongue. Language is said to conceal thought,
Morphological, biochemical, and electrophysiological characterization of a clonal cell (H9c2) line from rat heart.
Authors: J Hescheler, R Meyer, S Plant, D Krautwurst, W Rosenthal, G Schultz
Journal: Circulation Research (1991)

Morphological, electrophysiological, and biochemical properties of H9c2 cells, a permanent cell line derived from rat cardiac tissue, were studied. Although the lectin binding pattern revealed similar sugar residues in the surface coat of H9c2 cells and isolated rat cardiocytes, heart-specific morphological structures could not be detected in H9c2 cells. Under physiological ionic conditions, H9c2 cells exhibited an outwardly rectifying, transient K+ current. When this current component was blocked by Ba2+ and Cs+, we observed an inward current through Ca2+ channels (15.8 +/- 2.2 pA/pF, n = 18, measured as Ba2+ current) that showed all characteristics of cardiac L-type currents. The activation kinetics were fast, and the current was stimulated by isoproterenol. The effect of isoproterenol was mimicked by forskolin or intracellularly applied cAMP. In radioligand binding experiments, we identified a specific, saturable, stereoselective and reversible high-affinity [3H]-(+)PN 200-110 binding with a dissociation constant Kd = 0.53 +/- 0.28 nM and a maximal specific binding of Bmax = 129.3 +/- 16.1 fmol/mg protein. There was an additional low-affinity/high-capacity binding site, which is unlikely to be related to a Ca2+ channel protein. Signal-transducing G proteins in membranes were characterized by [32P]ADP-ribosylation catalyzed by bacterial toxins and by the use of various antibodies. Cholera toxin substrates of 42 and 45 kd were identified that apparently correlated to Gs alpha-subunits. Pertussis toxin substrates of 40-41 kd were tentatively identified as Gi alpha-subunits. The G protein Go was absent or at least extremely low in concentration.
Cause of Genuine Autoregulation of the Renal Circulation
Authors: WILLIAM H. WAUGH, ROBERT G. SHANKS
Journal: Circulation Research (1960)

The mechanism causing renal vascular flow to vary less than proportional to changes in arterial-venous pressure gradient, was studied in isolated dog kidneys perfused with whole blood and with cell-free colloidal solutions. This autoregulation of renal flow rapidly deteriorated along with vascular reactivity to drugs when oxygenated polyvinyl-pyrrolidone-Locke solution was used for perfusion. This deterioration was prevented by the addition of plasma to the colloidal perfusate. During the first 2 seconds of suddenly raised arterial pressure, renal flow normally increased proportionately or slightly more than proportionately to the increase in arterial pressure; intrarenal venous pressure, needle tissue pressure and kidney weight rose simultaneously. During the next 4 seconds, increasing vascular resistance upstream from the intrarenal veins caused parallel reductions in renal flow, intrarenal venous pressure, needle tissue pressure and at times kidney weight. After brief rhythmical changes in prevenous segmental resistance, flow became steady to show intense autoregulation, while intrarenal venous pressure and needle tissue pressure remained relatively low. This genuine autoregulation of renal flow was abolished by cooling kidneys to 3 to 10 C, and by treatment with chloral hydrate and with procaine in concentrations rendering the smooth muscle of the renal blood vessels relatively inert to direct drug stimulants. On the other hand, at temperatures of 3 to 10 C., and usually with chloral hydrate treatment, a factitious and passive type of flow autoregulation was observed, caused by the effects of abnormally high tissue pressures. Renal flow autoregulation was not appreciably impaired by anesthetization of the intrarenal nerves by procaine in concentrations which did not simultaneously depress vascular smooth muscle reactivity. Yohimbine induced sympatholysis did not impair autoregulation, and Dibenzyline treatment to intrarenal sympatholysis depressed only slightly autoregulation of renal flow. It was not inhibited by γ-aminobutyric acid. Anoxic perfusion which did not appreciably depress the reactivity of intrarenal autonomic ganglia, impaired autoregulation moderately. The loss of autoregulation of renal flow, accompanied by vasoconstriction following severe hemorrhage in the kidney donor dog, was slowly reversible upon perfusion of the subsequently isolated kidney and was related to smooth muscle contracture within the arterial-arteriolar vasculature. It is concluded, that myogenic vasomotion in the renal arterial-arteriolar tree in response to the level of transmural vascular pressure is the fundamental cause of genuine renal circulatory autoregulation. It is furthermore suggested that the myocytes of the juxtaglomerular apparatus may act as myogenic pacemakers in the vasomotion responsible for the essentially perfect autoregulation of the normal kidney.
Transferable beta-lactamase. A new mechanism for in vitro penicillin resistance in Streptococcus faecalis.
Authors: B E Murray, B Mederski-Samaroj
Journal: Journal of Clinical Investigation (1983)

Although enterococci are relatively resistant to penicillin, the mechanism of resistance is largely unknown and enzymatic inactivation does not play a role. In this study, an isolate of Streptococcus faecalis was found to have beta lactamase activity resulting in complete inactivation of penicillin. With a high inoculum, this strain was resistant to greater than 1,000 micrograms/ml of penicillin. Penicillin resistance and beta lactamase activity were transferred by conjugation at a high frequency to an enterococcal laboratory recipient strain together with two plasmids of molecular size 34 X 10(6) and 56 X 10(6), thus demonstrating the emergence of plasmid-mediated penicillin resistance in the genus Streptococcus.
Combined Surfactant Therapy and Inhaled Nitric Oxide in Rabbits with Oleic Acid-induced Acute Respiratory Distress Syndrome
Authors: GUANG FA ZHU, BO SUN, SHAN FU NIU, YING YUN CAI, KE LIN, ROBERT LINDWALL, BENGT ROBERTSON
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

Intratracheal administration of surfactant and inhaled nitric oxide (INO) have had variable effects in clinical trials on patients with acute respiratory distress syndrome (ARDS). We hypothesized that combined treatment with exogenous surfactant and INO may have effects in experimental ARDS. After intravenous infusion of oleic acid in adult rabbits and 4-6 h of ventilation, there was more than a 40% reduction in both dynamic compliance (Cdyn) of the respiratory system and functional residual capacity (FRC), a 50% increment of respiratory resistance (Rrs), a 70% reduction in PaO2 /FIO2, and an increase in intrapulmonary shunting (Q S/Q T) from 4.4 to 33.5%. The animals were then allocated to groups receiving (1) neither surfactant nor INO (control), (2) 100 mg/kg of surfactant (S) administered intratracheally, (3) 20 ppm INO (NO), or (4) 100 mg/kg of surfactant and 20 ppm INO (SNO), and subsequently ventilated for 6 h. After the period of ventilation, the animal lungs were used for analysis of disaturated phosphatidylcholine (DSPC) and total proteins (TP) in bronchoalveolar lavage fluid (BALF), and for determination of alveolar volume density (VV). The animals in the control group had the lowest survival rate, and no improvement in lung mechanics and blood oxygenation, whereas those in the S group had a modest but statistically significant improvement in Cdyn, Rrs, PaO2 and FRC, reduced Q S/Q T, lowered minimum surface tension (gammamin) of BALF, and increased DSPC/ TP and alveolar VV. The NO group had increased PaO2 and reduced Q S/Q T. The SNO group showed improved Cdyn, Rrs, FRC, DSPC/TP, alveolar VV, and gammamin of BALF comparable to the S group, but there was a further increase in survival rate and PaO2, and additional reduction in Q S/Q T and TP in BALF. These results indicate that, in this animal model of ARDS, a combination of surfactant therapy and INO is more effective than either treatment alone.
Mechanistic insight into polysaccharide use within the intestinal microbiota
Authors: David N. Bolam, Justin L. Sonnenburg
Journal: Gut Microbes (2011)

It is becoming increasingly clear that diet is one of the major factors that drives the function and composition of the intestinal microbiota. The diet of humans is highly diverse when considering different populations or even a single individual over a relatively short period of time. However, we are just beginning to understand the mechanisms that connect dietary change to intestinal microbiota dynamics. The community of microbes within our distal digestive tract influences numerous aspects of our biology, and aberrant shifts in its composition appear to be associated with several diseases. It is, therefore, necessary to understand how our behaviour and environmental factors, such as changes in diet, impact our intestinal residents. Here we look to recent work to highlight some of the major questions on the horizon for understanding the key role that the Bacteroidetes play in the commerce of dietary polysaccharides within the intestine.
The effect of speed cameras on injuries from road accidents
Authors: R. West
Journal: BMJ (1998)

When motor cars first appeared on British roads they had to be preceded by a man waving a red flag to warn the public of the approaching danger. As the number of vehicles has grown, many ways of ensuring the orderly management of traffic and public safety have been tried. Despite improvements in vehicle and road design, traffic regulation, and driver behaviour and despite reductions in accident rates, road traffic accidents remain a major cause of premature death or serious injury.1 Can anything further be done to reduce this toll?

The epidemiology of road traffic accidents is well known. For prevention the most important measures are separation—of streams of traffic from …
968-30 Does Insertion/Deletion Polymorphism of the Angiotensin Converting Enzyme Influence the Occurrence of Restenosis After Percutaneous Transluminal Coronary Angioplasty?
Authors: Martial Hamon, Christophe Bauters, Carole Amant, Eugène Mc Fadden, Nicole Helbeque, Jean-Marc Lablanche, Michel Bertrand, Philippe Amouyel
Journal: Journal of the American College of Cardiology (1995)
Calcium and vitamin D in preventing fractures: Vitamin K supplementation has powerful effect
Authors: Thomas E Radecki
Journal: BMJ (2005)

Calcium and vitamin D in preventing fractures Vitamin K supplementation has powerful effectEditor-Porthouse et al conducted a good randomised controlled trial of calcium and supplementation with cholecalciferol (vitamin D 3 ) for prevention of fractures in primary care. 1 However, vitamin D and calcium are not enough.No mention was made of the extensive research from Japan and the Netherlands, which shows that vitamin K supplementation has a powerful effect in decreasing osteoporosis and osteoporosis related fractures.Combining vitamin K, vitamin D, and calcium seems ideal.Researchers from Osaka Medical College showed that vitamin K and vitamin D together increased bone density much better than vitamin K alone. 2hen comparing calcium and vitamin D alone with placebo, researchers at the University of Maastricht found little benefit on bone loss.But those randomised to take vitamin K in addition to calcium and vitamin D had significantly less femoral neck bone loss after three years. 3he Yamaguchi osteoporosis prevention study showed that vitamin K alone reduced vertebral fractures by 56% compared to placebo, comparable to the benefit found from etidronate. 4 Researchers at Hirosaki University in Japan showed that vitamin K lowered bone fractures in elderly female patients with Parkinson's by 90%. 5 The same research team showed an 86% decrease in fractures in elderly patients with Alzheimer's treated with a combination of vitamin K, vitamin D, and calcium compared with placebo.w1 If the medical standard became to first use vitamins D and K with calcium before using bisphosphonates or selective oestrogen receptor modulators, the public would save billions of dollars a year.