tbuckley/cabot-search huggingface dataset:
THE DELETERIOUS EFFECT IN DOGS OF A DRY PROTEIN RATION 1
Authors: T. S. Danowski, J. R. Elkinton, A. W. Winkler
Journal: Journal of Clinical Investigation (1944)

The present study seeks to determine whether dry protein without additional water increases dehydration.It was undertaken in a search for information whereby the survival time of individuals with inadequate supplies of water could be prolonged.Dogs deprived of food only, or of all intake, served as controls.The experimental variants included dry protein, dry carbo- hydrate, mixtures of dry protein and carbo- hydrate, fresh fillets of fish, and 20 per cent urea solution.Balances of water, electrolytes, and nitrogen were determined and the physiological reactions of the animals observed. MATERIAL AND METHODSAdult dogs were used throughout.Fourteen animals were fasted without water as controls.Data from 8 of * Water withheld or administered as indicated in Table IB.
Hypernatremia Induced by Maximal Exercise
Authors: Philip Felig
Journal: JAMA (1982)

A short burst of intensive exercise (100-m swim lasting one minute and resulting in a 12-fold rise in the level of blood lactate) resulted in frank hypernatremia (serum sodium level, &gt;150 mEq/L) in 30% to 40% of well-trained athletes. In contrast, less intensive exercise (800-m swim lasting ten minutes and resulting in a sevenfold rise in the level of blood lactate) failed to cause a rise in serum sodium level despite comparable elevations in hematocrit reading and serum protein levels. Hypernatremia induced by intensive exercise cannot be explained by losses in body fluid or solute ingestion, but is probably a consequence of a shift of hypotonic fluid from the extracellular to the intracellular compartment. Thus, the mechanism of exercise-induced hypernatremia may be unique, as compared with other clinically recognized forms of hypernatremia. (<i>JAMA</i>1982;248:1209-1211)
Subcontracts for Community Development and Service
Authors: HARVEY M. FREED
Journal: American Journal of Psychiatry (1972)

Subcontracts for certain services were awarded two years ago by an inner-city community mental health center to two community organizations that seemed to exemplify the growing spirit of pride that was emerging in the black community. The author describes the problems that developed, especially in regard to recruiting and retaining professional personnel, and the approaches to their solution. There have been both failures and successes: prevention programs have not yet taken hold, but the parent organizations have become more responsive to community needs.
Modulation of the atopy patch test: tacrolimus 0.1% compared with triamcinolone acetonide 0.1%
Authors: J. M. Oldhoff, E. F. Knol, M. Laaper‐Ertmann, C. A. F. M. Bruijnzeel‐Koomen, M. S. de Bruin‐Weller
Journal: Allergy (2006)

Background: The atopy patch test (APT) is an in vivo model to study the induction of eczema by inhalant allergens in atopic dermatitis patients. We studied the effect of pretreatment with topical tacrolimus 0.1% on APT in nonlesional skin of patients with atopic dermatitis. Methods: Nonlesional skin of the back of patients with atopic dermatitis ( n = 8) was treated once daily for 3 weeks with tacrolimus 0.1% ointment. Cetomacrogol ointment (placebo) was used as a negative control and triamcinolone acetonide 0.1% ointment as positive control. Twenty‐four hours after the last APT application, samples were taken from the three treated areas ( t = 0 and 24 h) for immunohistochemical analysis. Results: Pretreatment with tacrolimus ointment did not suppress nonlesional skin infiltrate, in contrast to triamcinolone acetonide. Furthermore, tacrolimus did not inhibit the induction of the APT macroscopically ( t = 24 h). An equal influx of T cells, eosinophils, dendritic cells, CD64+ and Fc ɛ RI‐positive cells was present compared with placebo. Only CD36+ and CD68‐positive cells were inhibited compared with placebo. All cell types were significantly inhibited in triamcinolone acetonide‐treated sites compared with placebo. Conclusions: Pretreatment with tacrolimus 0.1% ointment does not inhibit the APT reaction in patients with atopic dermatitis.
QUESTIONS ON THE ETIOLOGY OF SOME FORMS OF LENTICULAR OPACITY.
Authors: J. L. THOMPSON
Journal: JAMA (1883)

[Presented to the Section on Ophthalmology, Otology and Laryngology, June, 1883.] In looking over my records of cases for a number of years back, affections of the crystalline lens are found to sustain a relation of 9 per cent, and of these, a very large majority are opacities, idiopathic, and traumatic, mostly the former. In these I have been very much struck by the very large number which have taken place below, as compared with the upper peripheral portion of the lens, and still more surprised at seeing the opacity so often at the lower-inner margin. On first meeting with these, my practice was to inform those who were so affected that they had commencing cataracts, and I usually requested them to call on me from year to year that I might watch their progress toward ripeness, but after observing serving them for a number of years and seeing no
Intracardiac Electrocardiography in the Analysis and Understanding of Cardiac Arrhythmias
Authors: BRUCE N. GOLDREYER
Journal: Annals of Internal Medicine (1972)

Cardiac arrhythmias have recently been studied with techniques not previously available in clinical investigation. Catheterization techniques allow depolarization of discrete areas of the cardiac conduction system to be recorded when their electrical signals are of insufficient magnitude to generate potential differences at the body surface. Intracardiac stimulation sequences permit spontaneous arrhythmias to be replicated, initiated, and terminated, thereby not only suggesting their probable electrophysiological mechanisms but also new modes of therapy. The techniques of intracardiac electrocardiography are reviewed, and their application to the recognition and understanding of common cardiac arrhythmias—sinus dysrhythmias, premature depolarizations, atrial tachycardias, atrial flutter and fibrillation, ventricular tachycardia, A-V conduction, and A-V block—is discussed.
The Ascent and Decline of Chloroquine
Authors: David J. Wyler
Journal: JAMA (1984)

The article by Harry Most and colleagues in a 1946 issue ofThe Journalwas the first report in the American medical literature on the efficacy of chloroquine (a 4-aminoquinoline) as an antimalarial agent in humans. This study of roughly 300 military personnel who had acquired vivax malaria during World War II demonstrated the superiority of chloroquine over quinacrine (the only synthetic antimalarial compound used clinically at that time) and quinine (an active alkyloid present in cinchona bark extracts, which were used for centuries). The report represented a milestone on the long and winding road toward a highly efficacious and relatively nontoxic synthetic antimalarial agent (reviewed in detail in reference 1) and began a period of about three decades during which the drug served an important role in malaria control programs in endemic areas. Unfortunately, the days of chloroquine's greatest glory were numbered. In 1961, the first report<sup>2</sup>of
[756] THE LIPIDOMICS OF NONALCOHOLIC FATTY LIVER DISEASE (NAFLD): A COMPARISON OF HUMAN DISEASE AND AN INSULIN RESISTANT MOUSE MODEL
Authors: P. Puri, R.A. Baillie, M. Wiest, F. Mirshahi, S.K. Erickson, A.J. Sanyal
Journal: Journal of Hepatology (2007)
Letter: Defects in sphygmomanometers.
Authors: S Conceicao, M K Ward, D Kerr
Journal: BMJ (1976)

hours after dosing, by 7-16",, 16 hours after dosing, and by 8-13",, 24 hours after dosing.Thus once-daily therapy with sotalol has a 24-hour effect in reducing blood pressure.(2) The dose of sotalol eventually required was related to the initial diastolic blood pressure.(3) In at least one patient there appeared to be a correlation between standing diastolic pressure, heart rate, and sotalol dosage.
Serum Levels of Surfactant Proteins A and D Are Useful Biomarkers for Interstitial Lung Disease in Patients with Progressive Systemic Sclerosis
Authors: HIROKI TAKAHASHI, YOSHIO KUROKI, HIROSHI TANAKA, TSUKASA SAITO, KEIZO KUROKAWA, HIROFUMI CHIBA, AKIRA SAGAWA, HISATO NAGAE, SHOSAKU ABE
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

To find a less-invasive and lung-specific clinical biomarker, we measured serum levels of surfactant proteins A and D (SP-A and SP-D) by sandwich enzyme-linked immunosorbent assays in 42 patients with progressive systemic sclerosis (PSS) to evaluate their significance in relation to the presence of interstitial lung disease (ILD) and to assess their diagnostic merits. The patients were divided into two groups based on findings by chest computed tomography (CT): 30 patients with ILD (CT-positive ILD group), and 12 patients without any lung abnormalities (CT-negative ILD group). The CT-positive ILD group was further divided into two groups: 24 patients with ILD detectable by chest plain radiography (X-ray-positive ILD group) and six patients with ILD showing no abnormality (X-ray-negative ILD group). The levels of SP-A and SP-D in sera were significantly higher in the CT-positive ILD group than in the CT-negative ILD group. They were also significantly higher in the X-ray-positive ILD group than in the CT-negative ILD group. In the X-ray-negative ILD group, their levels were higher than those of the CT-negative ILD group. We next estimated sensitivity and specificity of SP-A, SP-D, and X-ray for detecting ILD on CT. Sensitivity of SP-D was high (77%) as well as that of X-ray (80%), whereas SP-A showed a low sensitivity (33%). Remarkably, five of six patients in the X-ray-negative ILD group showed SP-D concentrations over its cut-off level, thereby demonstrating that an SP-D assay contributes to the detection of ILD overlooked by X-ray. Moreover, a combination of X-ray and SP-D dramatically increases sensitivity to 97%. Specificity of SP-A, SP-D, and X-ray to the CT-negative ILD group was 100%, 83%, and 100%, respectively. In conclusion, this study indicates that elevated levels of serum SP-A and SP-D reflect well the presence of ILD and that the combination of SP-D and X-ray contributes to reduce the risk of clinicians overlooking ILD complicated by PSS, although a repetition in another set of subjects is needed to confirm these indications.
OC-025 Expanded Cardia Mucosa Associated with Central Obesity Immunohistochemically Resembles Non-Im Barrett’S Mucosa
Authors: M H Derakhshan, E V Robertson, Y Y Lee, A A Wirz, J J Going, K E McColl
Journal: Gut (2013)

The NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome is a critical component of the innate immune system that is activated by microbial infections and cellular stress signals. The molecular mechanism of NLRP3 inflammasome activation remains not fully understood. As an NLRP3-interacting partner, NEK7 has emerged as a critical mediator for NLRP3 inflammasome activation. In contrast to NEK7, NEK6, the closely related member of the NEK family, does not support NLRP3 inflammasome activation. In this study, we show that the mouse NEK7 catalytic domain, which shares high sequence identity with the counterpart of NEK6, mediates its interaction with NLRP3 and inflammasome activation in mouse macrophages. Within their catalytic domains, a single amino acid residue at a corresponding position (R121<sup>NEK7</sup>, Q132<sup>NEK6</sup>) differentiates their function in NLRP3 inflammasome activation. Surprisingly, substitution of the glutamine residue to an arginine residue at position 132 confers NEK6 the ability of NLRP3 binding and inflammasome activation in mouse macrophages. Furthermore, our results suggest a structural pocket surrounding the residue R121 of NEK7 that is essential for NLRP3 binding and inflammasome activation.
Health Insurance Coverage and Utilization of Health Services by Mexican Americans, Mainland Puerto Ricans, and Cuban Americans
Authors: Fernando M. Treviño
Journal: JAMA (1991)

This investigation examines data on 13 000 Mexican Americans, Puerto Ricans, and Cuban Americans between 6 months and 74 years of age who were interviewed from 1982 through 1984 in the Hispanic Health and Nutrition Examination Survey. In addition, data from the 1989 Current Population Survey (N = 145 000) conducted by the US Bureau of the Census are presented for the white and black non-Hispanic populations as well as the three Hispanic national origin groups. The study revealed that over one third of the Mexican-American population, one fifth of the Puerto Rican population, and one fourth of the Cuban-American population is uninsured for medical expenditures compared with one fifth of the black, non-Hispanic population and one tenth of the white, non-Hispanic population. Furthermore, compared with Hispanics with private health insurance, uninsured Hispanics are less likely to have a regular source of health care, less likely to have visited a physician in the past year, less likely to have had a routine physical examination, and less likely to rate their health status as excellent or very good. (<i>JAMA</i>. 1991;265:233-237)
The 1991 Albert Lasker Public Service Award. Women's reproductive health. A chronic crisis
Authors: R. C. Duke
Journal: JAMA (1991)

WE COMMONLY think of family planning as a way for couples to choose when they have children and how many children they have. It is time to recognize the staggering impact of deficient family planning services on health. A worldwide death toll of more than 1 million women each year is caused by unsafe conditions of childbirth; risky, clandestine abortions; and sexually transmitted diseases.<sup>1,2</sup>The lives of approximately 3 million infants and children who now die each year could be saved by using family planning to avert unsafe patterns of childbearing.<sup>2,3</sup> <h3>POVERTY AND HEALTH</h3> Good health is highly dependent on an individual's social and economic setting. Wealthy nations can provide environments that offer protection from the diseases that flourish because of the crowding, malnutrition, and other conditions of poverty. It is easy to forget that the so-called tropical diseases, such as malaria and cholera, now rampant in many
Numbers of deaths related to intrapartum asphyxia and timing of birth in all Wales perinatal survey, 1993-5
Authors: J. H Stewart, J. Andrews, P. H T Cartlidge
Journal: BMJ (1998)

<h3>Abstract</h3> <b>Objectives:</b> To investigate the relation between the timing of birth and the occurrence of death related to an intrapartum event. <b>Design:</b> Analysis of 107 206 births to Welsh residents in 1993-5, including 608 cases of stillbirth and 407 of neonatal death identified in the all Wales perinatal survey, the cause of death classified with the clinicopathological system. <b>Subjects:</b> 79 normally formed babies stillborn or who died in the neonatal period, birth weight &gt;1499 g, for whom cause of death was related to an intrapartum event. <b>Main outcome measures:</b> Relative risk of death due to an intrapartum event according to the hour, day, and month of birth. <b>Results:</b> Mortality was higher in babies born between 9 00 pm and 8 59 am than in those born between 9 00 am and 8 59 pm; relative risk (95% confidence interval) 2.18 (1.37 to 3.47). July and August births also had a higher death rate than births in other months; relative risk 1.99 (1.23 to 3.23). Weekend births had a higher death rate but it was not significant. <b>Conclusions:</b> The excess of deaths at night and during months when annual leave is popular may indicate an overreliance on inexperienced staff at these times. Errors of judgment may also be related to physical and mental fatigue, demanding a more disciplined systematic approach at night. Mistakes may be ameliorated by increasing shiftwork, but shifts should be carefully designed to avoid undue disruption of circadian rhythms. In addition, greater supervision by senior staff may be required at night and during summer months. <h3>Key messages</h3> In low risk pregnancies the incidence of death due to intrapartum asphyxia is regarded as a sensitive measure of the quality of perinatal care Babies born at night and during summer months are at increased risk of death due to intrapartum asphyxia, raising concerns about variability in care around the time of delivery Errors of judgment may be related to mental fatigue. Staff need to be aware of how their performance may vary, and a more disciplined systematic approach at night may be needed Greater supervision by senior staff may be required at night and during summer months
CD44 Expression Denotes a Subpopulation of Gastric Cancer Cells in Which Hedgehog Signaling Promotes Chemotherapy Resistance
Authors: Changhwan Yoon, Do Joong Park, Benjamin Schmidt, Nicholas J. Thomas, Hae-June Lee, Teresa S. Kim, Yelena Y. Janjigian, Deirdre J. Cohen, Sam S. Yoon
Journal: Clinical Cancer Research (2014)

Abstract Purpose: Gastric cancers may harbor a subset of cells with cancer stem cell (CSC) properties, including chemotherapy resistance, and CD44 is a gastric CSC marker. The Hedgehog (HH) pathway is a key developmental pathway that can be subverted by CSCs during tumorigenesis. Here, we examine the role of HH signaling in CD44(+) gastric cancer cells. Experimental Design: Gastric cancer cell lines, tumor xenografts, and patient tumors were examined. Results: Gastric cancer cell lines AGS, MKN-45, and NCI-N87 grown as spheroids or sorted for CD44(+) were found to have upregulation of HH pathway proteins. HH inhibition using Smoothened (Smo) shRNA or vismodegib (VIS) decreased spheroid formation and colony formation. CD44(+) cells, compared with unselected cells, were also resistant to 5-fluorouracil and cisplatin chemotherapy, and this resistance was reversed in vitro and in xenografts with Smo shRNA or VIS. CD44(+) cells also had significantly more migration, invasion, and anchorage-independent growth, and these properties could all be blocked with HH inhibition. Clinical tumor samples from a phase II trial of chemotherapy with or without VIS for advanced gastric cancer were analyzed for CD44 expression. In the chemotherapy alone group, high CD44 expression was associated with decreased survival, whereas in the chemotherapy plus VIS group, high CD44 expression was associated with improved survival. Conclusions: HH signaling maintains CSC phenotypes and malignant transformation phenotypes in CD44(+) gastric cancer cells, and HH inhibition can reverse chemotherapy resistance in CD44(+) cells. Gastric cancer is a heterogeneous disease, and the strategy of combining chemotherapy with HH inhibition may only be effective in tumors with high CD44 levels. Clin Cancer Res; 20(15); 3974–88. ©2014 AACR.
Recombinant human CD19L-sTRAIL effectively targets B cell precursor acute lymphoblastic leukemia
Authors: Fatih M. Uckun, Dorothea E. Myers, Sanjive Qazi, Zahide Ozer, Rebecca Rose, Osmond J. D’Cruz, Hong Ma
Journal: Journal of Clinical Investigation (2015)

Patients with B cell precursor acute lymphoblastic leukemia (BPL) respond well to chemotherapy at initial diagnosis; however, therapeutic options are limited for individuals with BPL who relapse. Almost all BPL cells express CD19, and we recently cloned the gene encoding a natural ligand of the human CD19 receptor (CD19L). We hypothesized that fusion of CD19L to the soluble extracellular domain of proapoptotic TNF-related apoptosis-inducing ligand (sTRAIL) would markedly enhance the potency of sTRAIL and specifically induce BPL cell apoptosis due to membrane anchoring of sTRAIL and simultaneous activation of the CD19 and TRAIL receptor (TRAIL-R) apoptosis signaling pathways. Here, we demonstrate that recombinant human CD19L-sTRAIL was substantially more potent than sTRAIL and induced apoptosis in primary leukemia cells taken directly from BPL patients. CD19L-sTRAIL effectively targeted and eliminated in vivo clonogenic BPL xenograft cells, even at femtomolar-picomolar concentrations. In mice, CD19L-sTRAIL exhibited a more favorable pharmacokinetic (PK) profile than sTRAIL and was nontoxic at doses ranging from 32 fmol/kg to 3.2 pmol/kg. CD19L-sTRAIL showed potent in vivo antileukemic activity in NOD/SCID mouse xenograft models of relapsed and chemotherapy-resistant BPL at nontoxic fmol/kg dose levels. Together, these results suggest that recombinant human CD19L-sTRAIL has clinical potential as a biotherapeutic agent against BPL.
Beyond erythropoiesis: The anti-inflammatory effects of erythropoietin
Authors: Q FENG
Journal: Cardiovascular Research (2006)

See article by Li et al.  [4]  (pages 684–694) in this issue. 

Erythropoietin (EPO) is a 30.4-kDa glycoprotein essential for red blood cell production. In adults, EPO is produced primarily in the kidney via an oxygen-sensing mechanism and stimulates erythroid progenitors in the bone marrow to increase red blood cell mass. In addition to its role in erythropoiesis, EPO has been shown to protect against ischemic injury in several organs including the heart. In various animal models, administration of EPO reduces infarct size and improves cardiac function following myocardial ischemia and reperfusion (I/R). The protective effects have been observed regardless of whether EPO was administered before ischemia, at the onset of ischemia, or at reperfusion [1,2].

The protective effects of EPO are also seen in chronic models of myocardial infarction (MI). In this regard, treatment of EPO before or immediately after coronary artery ligation decreases cardiac remodeling and improves myocardial function. Interestingly, a single dose of EPO (3000 IU/kg, i.p.) immediately after induction of MI improved cardiac function measured 8 weeks later. The therapeutic relevance of EPO was further demonstrated by van der Meer et al., who showed that EPO treatment started 3 weeks after MI improved cardiac function in a rat model of heart failure [3]. Consistent with this finding, in a report in this issue of Cardiovascular Research , EPO was started 6 weeks after induction of MI when heart failure was fully established in mice. Four weeks of EPO treatment diminished left … 

* Tel.: +1 519 685 8300x55443; fax: +1 519 685 8341. Email address: qfeng{at}uwo.ca
Drugs Spotlight Program
Authors: THOMAS DETRE
Journal: Annals of Internal Medicine (1978)

Menopause is merely a clinically discernible clue symbolic of the multitude of changes preceding or following the cessation of menses by many years. Because of the time span involved, separating changes observed in the menopausal transition from other age-related maturational events presents serious methodologic problems. Of the host of psychologic and psychosomatic symptoms, only hot flushes and associated sweats occur more frequently in this epoch, while an interplay between hormonal and age-related effects is assumed in atrophic changes involving the genitourinary organs. The relation between menopause and osteoporosis is suggestive but by no means proven, as is the risk for cardiovascular disease. Empiric evidence points to the usefulness of estrogen for the management of vasomotor instability, the symptoms associated with atrophy of the genitourinary tract, and in the prophylaxis of osteoporosis, but not in the treatment of anxiety, depression, and other psychiatric disorders.
Smoking and renal artery stenosis.
Authors: A Mackay, J J Brown, A M Cumming, C Isles, A F Lever, J I Robertson
Journal: BMJ (1979)

OPCS Smoking and renal artery stenosisCigarette smoking appears to be commoner in patients with malignant- phase hypertension than in the general population or in patients with non-malignant hypertension.1 2 We have also found an excess of smokers among premenopausal women with hypertension and ischaemic heart disease.3We report a study of the smoking habits of 85 hypertensive patients with renal artery stenosis.* P <005.t P <0 01.+ P <0 001.NS= Not significant: P >0 05.