tbuckley/cabot-search huggingface dataset:
Chronic exercise training protects aged cardiac muscle against hypoxia.
Authors: J Y Wei, Y Li, T Lincoln, W Grossman, D Mendelowitz
Journal: Journal of Clinical Investigation (1989)

To test the hypothesis that chronic exercise may improve tolerance to hypoxia in aged hearts, we compared cardiac function of exercised rats to that of their age-matched, nonexercised controls. Right ventricular papillary muscles were removed from young adult (9 mo) and old (24-26 mo) male Fischer 344 rats that were chronically exercised on a rodent treadmill and from their age-matched, nonexercised controls. During isometric contraction, hypoxia depressed contraction and relaxation in all muscles, but to a lesser extent in the exercised groups. A significant exercise effect was observed in the following variables: the maximum developed tension, the maximum rate of tension development, the maximum rate of tension decline, and the time required for the hypoxia to reduce maximum tension by 20%. The maximum rate of tension decline was more sensitive to hypoxia than was the maximum rate of tension development in all groups. Exercise also had an effect on the temperature dependence of cardiac performance during hypoxia. Thus, chronic exercise results in the preservation of both contraction and relaxation during hypoxia for aged as well as young adult hearts.
REFERENT BODY WEIGHT VALUES IN OVER GROUND WALKING, OVER GROUND JOGGING, TREADMILL JOGGING, AND ELLIPTICAL EXERCISE
Authors: Y Kaplan, E Witvrouw, M Nyska, E Palmanovich, Y Barak
Journal: British Journal of Sports Medicine (2014)

Background In order to make reliable clinical decisions in relation to when injured or surgically operated athletes may return to daily functional and weight-bearing sporting activities, there is a need to establish referent average weight-bearing values in common sporting activities. Objectives To evaluate average percentage body weight (APBW) values and weight-bearing distribution percentages (WBDP) between sports activities in a referent adult population, and to suggest clinical implications. Design Original research study. Setting Lerner Sports Center, Hebrew University, Mount Scopus, Jerusalem, Israel. Participants 75 asymptomatic volunteers, mean age=33.5(19–72) years SD=15.1, mean weight (kg)=70.7 (43–113) SD=14.1. Interventions 4 tests were conducted: 1. Overground walking (OGW) over a 20m distance, 2. Overground jogging (OGJ) over a 20m distance, 3.Treadmill jogging (TJ) at a constant speed of 8.5 km/hr for a 15-second interval and 4. Elliptical exercise (EE) for a 20 second period at a resistance and incline level of 10, and a steady pace within the range of 70–95 steps/min. Main outcome measure The Smartstep™ weight-bearing gait analysis system. Results The APBW value on the entire foot in OGW was 112% (SD=15.57), in OGJ, 201% (SD=31.24, in TJ, 175% (SD=25.48) and in EE, 73% (SD=13.8). Regarding WBDP, the swing phase in OGJ and TJ was significantly longer than the stance phase (P&lt;.05). Conclusions EE significantly reduces weight-bearing as compared to other common functional and sporting activities. This information is also useful from a repetitive loading standpoint (to prevent overuse injury) or for exercise recommendations for those at greater risk for exacerbating chronic joint pathology.
Plasminogen Activator Inhibitor Type 1 Enhances Neointima Formation After Oxidative Vascular Injury in Atherosclerosis-Prone Mice
Authors: Yanhong Zhu, Peter M. Farrehi, William P. Fay
Journal: Circulation (2001)

Background —Plasminogen activator inhibitor type 1 (PAI-1) inhibits neointima formation after vascular injury. Hyperlipidemia modulates the expression of multiple genes, however, and the effects of PAI-1 on the arterial response to injury under hyperlipidemic conditions are unknown. The purpose of this study was to examine the impact of PAI-1 on intimal hyperplasia and other vascular changes that develop after arterial injury in apolipoprotein E–deficient (apoE −/− ) mice. Methods and Results —Ferric chloride injury of the midportion of the common carotid arteries of apoE −/− mice (n=22) induced formation of a neointima that contained smooth muscle cells, foam cells, neutral lipid, tissue factor, and von Willebrand factor. Interactions between vascular injury and apolipoprotein E deficiency were strongly synergistic; either stimulus alone was insufficient to induce significant neointima formation. Mean intima/media ratios were significantly greater ( P &lt;0.03) in apoE −/− , PAI-1 +/+ mice (5.6±1.8, n=12) than in apoE −/− , PAI-1 −/− mice (1.2±0.55, n=12), as were the percentages of bromodeoxyuridine-positive cells in the intima and media ( P &lt;0.03). Transiently occlusive (&lt;48 hours) and nonocclusive mural thrombi persisted longer in apoE −/− , PAI-1 +/+ mice than in apoE −/− , PAI-1 −/− mice. Conclusions —In atherosclerosis-prone mice, PAI-1 promotes neointima formation after oxidative vascular injury. The apparent hyperlipidemia-dependent effect of PAI-1 may be mediated by its capacity to inhibit the clearance of platelet-fibrin thrombi that can deliver growth factors to the blood vessel wall or be incorporated into developing vascular lesions. Alternatively, hyperlipidemia may alter the pattern of gene expression in the blood vessel wall to enhance potential effects of PAI-1 on antiproliferative processes, such as transforming growth factor-β activation and apoptosis.
Dipyridamole Stress Echocardiography for Risk Stratification in Hypertensive Patients With Chest Pain
Authors: Lauro Cortigiani, Emilio A. Paolini, Eugenio Nannini
Journal: Circulation (1998)

Background —The noninvasive prognostic assessment of coronary artery disease (CAD) in hypertensive patients represents an unresolved task to date. In this study, we investigated the value of dipyridamole stress echocardiography in risk stratification of hypertensive patients with chest pain and unknown CAD. Methods and Results —Dipyridamole stress echocardiography was performed in 257 hypertensives (110 men; age, 63±9 years) complaining of chest pain and without a history of CAD. No major complications occurred. Four tests were interrupted prematurely because of side effects, with 98.4% feasibility of test. A positive echocardiographic response was found in 72 patients (27 during the low-dose [≤0.56 mg/kg] and 45 during the high-dose [&gt;0.56 mg/kg]). During the follow-up (32±18 months), 27 cardiac events occurred: 3 deaths, 8 infarctions, and 16 cases of unstable angina. Moreover, 27 patients underwent coronary revascularization. At multivariate analysis, the positive echocardiographic result (OR, 5.5; 95% CI, 1.4 to 16.6) was the only predictor of hard cardiac events (death, infarction). Considering spontaneous cardiac events (death, infarction, and unstable angina) as end points, the positive echocardiographic result (OR, 4.2; 95% CI, 1.8 to 9.6) and family history of CAD (OR, 4.2; 95% CI, 1.5 to 6.9) were independently associated with prognosis. The 3-year survival rates for the negative and the positive populations were, respectively, 97% and 87% ( P =0.0019) considering hard cardiac events and 96% and 74% ( P =0.0000) considering spontaneous cardiac events. Conclusions —Dipyridamole stress echocardiography is safe, highly feasible, and effective in risk stratification of hypertensives with chest pain and unknown CAD. At present, it represents an attractive option for prognostic assessment of this clinically defined population.
Visceral Afferent Neuropathy in Diabetic Gastroparesis
Authors: Wolfgang Rathmann, Paul Enck, Thomas Frieling, F Arnold Gries
Journal: Diabetes Care (1991)

Objective To determine whether a lack of symptoms in diabetic patients with gastrointestinal motility disorders is associated with visceral afferent neuropathy. Research Design and Methods We investigated cerebral evoked potentials (EPs) after esophageal stimulation in 10 patients with motor dysfunction of the gastrointestinal tract and in 10 healthy control subjects. All patients had insulin-dependent diabetes mellitus (5 men, 5 women, age range 31–60 yr, diabetes duration 8–36 yr, 10 of 10 with polyneuropathy, 6 of 10 with cardiac autonomic neuropathy). Their esophageal and gastric motor disorders had been diagnosed by scintigraphy, and gastrointestinal stenosis had been excluded by gastroscopy. Only 2 patients had severe symptoms, whereas 6 patients complained of minor discomfort (distension, bloating), and 2 patients were symptom free. Results EPs were recorded after electrical stimulation of the esophagus (32 cm from the incisors) at intensity just above the perception threshold. All control subjects exhibited regular EPs at 0.1 ms/30 mA stimulation intensity. In 6 diabetic patients, no EPs were detected at 0.1 and 0.3 ms/30 mA, and the perception thresholds were significantly elevated. In 4 patients with normal perception threshold, EPs of regular shape but decreased amplitude were recorded. These patients had mild or severe gastroparetic complaints. Conclusions These data show for the first time an association between a lack of symptoms in diabetic gastrointestinal motility disorders and visceral afferent neuropathy.
MALIGNANT ATROPHIC PAPULOSIS (DEGOS' DISEASE) TWO CASES OCCURRING IN THE SAME FAMILY
Authors: PATRICK HALL-SMITH
Journal: British Journal of Dermatology (1969)

SUMMARY.— Malignant atrophic papulosis occurring in mother and son is described. Hitherto this condition has not been described in 2 members of the same family nor, to our knowledge, have there been previously reported cases from the U.K. Genetic and environmental factors involved in the pathogenesis of this disease are discussed.
Abstract 2253: New targets of mTORC1 pathway in ER-positive cells
Authors: Anna Sedletcaia, Helen A. Unger, Naamah Plotzker, Marina K. Holz
Journal: Cancer Research (2012)

Abstract mTOR complex 1 (mTORC1) regulates protein translation, autophagy, and cell growth. These cellular functions are often dysregulated in cancer, therefore identification of mTORC1 targets in control of these processes is of great interest for development of targeted cancer therapies. While rapamycin shown an effect in early clinical trials, the effectiveness of rapamycin in treatment of breast cancer has been variable. Estrogen receptor (ER) ≤ mediates the proliferative effects of estrogen and represents an important clinical target in treatment of ER-positive cancers. Tamoxifen is an anti-estrogen that has become the standard agent for the treatment of ER-positive breast cancer, where it acts as an antagonist. However, resistance to tamoxifen, and other endocrine or anti-estrogen therapies develops in many cases. One mechanism by which resistance develops is through phosphorylation of ERα, allowing it to act in estrogen-independent manner. Phosphorylation of Ser118 and Ser167 is important for transcriptional activity of ERα. The regulation of these sites is complex, involving inputs from the mTOR and MAPK signaling pathways. Importantly, ERα phosphorylation correlates with resistance to tamoxifen, and is a prognostic marker for disease progression and survival. Therefore, the goal of our study is to identify new targets of mTORC1 pathway important for growth and proliferation of ER-positive cells. Thus, inhibition of downstream components of the mTORC1 pathway together in combination with anti-estrogen therapy may prove to be an effective strategy in treatment of ER-positive cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2253. doi:1538-7445.AM2012-2253
Experiences with Ethamivan, a New Respiratory Stimulant and Analeptic Agent
Authors: Samuel Silipo
Journal: JAMA (1961)

THE purpose of this report is to describe our experiences with ethamivan (vanillic diethylamide [Emivan]) in the therapy of disorders associated with respiratory depression. Forty-three adult patients with clinical evidences of diffuse impairment of pulmonary air exchange were studied. These included 7 with barbiturate intoxication, 27 with severe chronic obstructive pulmonary emphysema, and 9 miscellaneous cases. Arterial blood was sampled anaerobically using a Cournand needle in 10 of the subjects with pulmonary emphysema. Gas contents were obtained by the method of Van Slyke and Neill<sup>1</sup>and the arterial CO<sub>2</sub>tension (Paco<sub>2</sub>) calculated from a line chart based on the Henderson-Hasselbach equation,<sup>2</sup>after the pH was determined with a Metrohm pH meter. <h3>Barbiturate Intoxication</h3> Our experiences with the 7 cases of barbiturate intoxication are summarized in Table 1. In the severely depressed patients (1 and 6), priming doses of 400 and 500 mg. of ethamivan were
Surgical Treatment of Morbid Obesity
Authors: John P. Callan
Journal: JAMA (1979)

The consensus reached at the National Institutes of Health Consensus Development Conference on surgical treatment of morbid obesity recently held in Bethesda, Md, was that surgical intervention in morbid obesity should be confined to persons who suffer from physical or emotional complications where medical methods have previously failed. Morbid obesity was defined by participants as 45 kg overweight or 200% or more of desirable weight, according to Metropolitan Life Insurance Company standards. While conferees agreed that conventional treatments of dieting and fasting are ineffective for most sufferers, they disagreed on preferred surgical technique for the condition. The two most common surgical procedures for overweight are jejunoileal intestine bypass and gastric bypass. The former is more established and contributes to greater weight loss, but it also involves more complications, such as severe diarrhea, flatulence, liver failure, arthritis, and possibly cancer of the colon, noted University of Minnesota surgeon Henry Buckwald, MD.
Hepatocellular carcinoma and African iron overload.
Authors: I T Gangaidzo, V R Gordeuk
Journal: Gut (1995)

Both hepatocellular carcinoma (HCC) and iron overload are important health problems in Africa. Chronic hepatitis B virus (HBV) infection is recognised as a major risk factor for HCC, but iron overload in Africans has not been considered in pathogenesis. Up to half the patients with HCC in Africa do not have any recognised risk factors such as preceding chronic HBV infection, and other risk factors remain unidentified. HCC is an important complication of HLA-linked haemochromatosis, an iron loading disorder found in Europeans. It is proposed that African iron overload might also be a risk factor for HCC.
Waardenburg's Syndrome — Report of a Case in a Non-Dutch Family
Authors: J. Richard Settelmayer, Michael Hogan
Journal: New England Journal of Medicine (1961)

IN 1951 Waardenburg1 first described the syndrome consisting of lateral displacement of the inner canthi of the eye and of the inferior lacrimal puncta (dystopia canthi medialis and punctorum lacrimalium lateroversa), high, broad nasal root, confluence of the eyebrows, with hypertrichosis of the medial parts (hyperplasia supercilii medialis and radicis nasi), partial or total heterochromia iridium, white forelock (albinismus circumscriptus pilorum) and unilateral or bilateral congenital deafness. Since the original description of this syndrome no cases have been reported in the American literature as such. A recent article by Partington,2 which called the syndrome to our attention, stated that only . . .
Two thromboxane A2 receptor isoforms in human platelets. Opposite coupling to adenylyl cyclase with different sensitivity to Arg60 to Leu mutation.
Authors: T Hirata, F Ushikubi, A Kakizuka, M Okuma, S Narumiya
Journal: Journal of Clinical Investigation (1996)

Thromboxane A2 (TXA2) receptor is a key molecule in hemostasis as its abnormality leads to bleeding disorders. Two isoforms of the human TXA2 receptor have been cloned; one from placenta and the other from endothelium, here referred to as TXR alpha and TXR beta, respectively. These isoforms differ only in their carboxyl-terminal tails. We report that both isoforms are present in human platelets. The two isoforms expressed in cultured cells show similar ligand binding characteristics and phospholipase C (PLC) activation but oppositely regulate adenylyl cyclase activity; TXR alpha activates adenylyl cyclase, while TXR beta inhibits it. The Arg60 to Leu mutant of TXR alpha, which has been shown to impair PLC activation (Hirata, T., A. Kakizuka, F. Ushikubi, I. Fuse, M. Okuma, and S. Narumiya. 1994. J. Clin. Invest. 94: 1662-1667), also impairs adenylyl cyclase stimulation, whereas that of TXR beta retains its activity to inhibit adenylyl cyclase. These findings suggest that the pathway linked to adenylyl cyclase inhibition might be involved in some of the TXA2-induced platelet responses such as shape change and phospholipase A2 activation which remain unaffected in the patients with this mutation.
Cardiorespiratory Fitness and Adiposity as Mortality Predictors in Older Adults
Authors: Xuemei Sui, Michael J. LaMonte, James N. Laditka, James W. Hardin, Nancy Chase, Steven P. Hooker, Steven N. Blair
Journal: JAMA (2007)

Although levels of physical activity and aerobic capacity decline with age and the prevalence of obesity tends to increase with age, the independent and joint associations among fitness, adiposity, and mortality in older adults have not been adequately examined.To determine the association among cardiorespiratory fitness ("fitness"), adiposity, and mortality in older adults.Cohort of 2603 adults aged 60 years or older (mean age, 64.4 [SD, 4.8] years; 19.8% women) enrolled in the Aerobics Center Longitudinal Study who completed a baseline health examination during 1979-2001. Fitness was assessed by a maximal exercise test, and adiposity was assessed by body mass index (BMI), waist circumference, and percent body fat. Low fitness was defined as the lowest fifth of the sex-specific distribution of maximal treadmill exercise test duration. The distributions of BMI, waist circumference, and percent body fat were grouped for analysis according to clinical guidelines.All-cause mortality through December 31, 2003.There were 450 deaths during a mean follow-up of 12 years and 31 236 person-years of exposure. Death rates per 1000 person-years, adjusted for age, sex, and examination year were 13.9, 13.3, 18.3, and 31.8 across BMI groups of 18.5-24.9, 25.0-29.9, 30.0-34.9, and > or =35.0, respectively (P = .01 for trend); 13.3 and 18.2 for normal and high waist circumference (> or =88 cm in women; > or =102 cm in men) (P = .004); 13.7 and 14.6 for normal and high percent body fat (> or =30% in women; > or =25% in men) (P = .51); and 32.6, 16.6, 12.8, 12.3, and 8.1 across incremental fifths of fitness (P < .001 for trend). The association between waist circumference and mortality persisted after further adjustment for smoking, baseline health status, and BMI (P = .02) but not after additional adjustment for fitness (P = .86). Fitness predicted mortality risk after further adjustment for smoking, baseline health, and either BMI, waist circumference, or percent body fat (P < .001 for trend).In this study population, fitness was a significant mortality predictor in older adults, independent of overall or abdominal adiposity. Clinicians should consider the importance of preserving functional capacity by recommending regular physical activity for older individuals, normal-weight and overweight alike.
TRPC Channels As Effectors of Cardiac Hypertrophy
Authors: Petra Eder, Jeffery D. Molkentin
Journal: Circulation Research (2011)

Transient receptor potential (TRP) channels of multiple subclasses are expressed in the heart, although their functions are only now beginning to emerge, especially for the TRPC subclass that appears to regulate the cardiac hypertrophic response. Although TRP channels permeate many different cations, they are most often ascribed a specific biological function because of Ca 2+ influx, either for microdomain signaling or to reload internal Ca 2+ stores in the endoplasmic reticulum through a store-operated mechanism. However, adult cardiac myocytes arguably do not require store-operated Ca 2+ entry to regulate sarcoplasmic reticulum Ca 2+ levels and excitation–contraction coupling; hence, TRP channels expressed in the heart most likely coordinate signaling within local domains or through direct interaction with Ca 2+ -dependent regulatory proteins. Here, we review the emerging evidence that TRP channels, especially TRPCs, are critical regulators of microdomain signaling in the heart to control pathological hypertrophy in coordination with signaling through effectors such as calcineurin and NFAT (nuclear factor of activated T cells).
Reversible Acute Renal Insufficiency and Hyperkalemia Following Indomethacin Therapy
Authors: Marilyn Galler, Vaughn W. Folkert, Detlef Schlondorff
Journal: JAMA (1981)

We noted five cases of reversible acute deterioration of renal function in patients with very mild to moderate renal insufficiency who received indomethacin for an acute gouty attack. This decrease in renal function was consistent with a primary decrease in renal blood flow. In addition, hyperkalemia developed in the patients, which we attribute to a decrease in renin and aldosterone secretion, a decrease in distal tubular delivery of sodium, and, more importantly, to a decrease in urine flow. This report is intended to alert physicians to the possible complications of indomethacin therapy in patients with mild renal insufficiency. (<i>JAMA</i>1981;246:154-155)
CELLS MEDIATING SPECIFIC IN VITRO CYTOTOXICITY
Authors: Pierre Golstein, Erik A. J. Svedmyr, Hans Wigzell
Journal: The Journal of Experimental Medicine (1971)

Spleen cells from mice immunized with allogeneic tumor cells are incubated on different fibroblast monolayers. The nonadsorbed cells are tested for cytotoxicity against (51)Cr-labeled target cells. The cytotoxicity of nonadsorbed cells is much lower after incubation on fibroblasts syngeneic to the immunizing tumor cells than after incubation on fibroblasts syngeneic to the immune cells. This specific decrease of cytotoxic activity depends on the duration and temperature of incubation on monolayers. After incubation the monolayers are trypsinized and pure populations of adsorbed lymphocytes isolated by density gradient fractionation. The cytotoxicity of such trypsin-eluted, gradient-purified lymphocytes is much higher when these lymphocytes are isolated from fibroblasts syngeneic to the immunizing tumor cells than when they are isolated from fibroblasts syngeneic to the immune cells. These experiments demonstrate specific adsorption of immune cells onto fibroblasts carrying the immunizing antigens, and thus prove the existence of specific receptors at the surface of these immune cells. Spleen cells from mice immunized with two types of allogeneic tumor cells bearing different H-2 antigen alleles are incubated on different fibroblast monolayers. The results of such experiments show a differential specific adsorption pattern, suggesting independent adsorption of two populations of immune cells bearing receptors directed against either one or the other immunizing H-2 antigen. The existence of at least a majority of cells, each of which is homogeneous as to the specificity of its receptors, makes it likely that specific receptors are synthetized by the cells that bear them. The role of specific receptor-bearing cells in the killing process is discussed.