tbuckley/cabot-search huggingface dataset:
CONSTIPATION AND FAULTY ELIMINATION AS A FACTOR IN DISEASE.
Authors: FREDERIC S. THOMAS
Journal: JAMA (1895)

The retention of fecal accumulations in the alimentary tract, and their discharge but once a day is an acquired habit. Primitive man, like other unrestrained animals, defecated more often. The result of retaining within the body matter so poisonous, can not be other than prejudicial to health. Man, the most perfect of animals, intellectually far in advance of all others, is nevertheless ignorant as to what food he should select. The result of this is imperfect digestion, constipation and faulty elimination. Each largely depends upon the other. Viewed from the standpoint of digestion, (intestinal,) let us briefly consider this important process. We are told that "harmony of the secretions means normal cell selection, and normal cell selection means health." Any deviation from these relations means "cell disturbance, or disease." The digestive changes in the small intestines may be summed up as follows: proteids are converted into peptones by pepsin and
Diagnosis and management of asthma in children
Authors: A. Bush, L. Fleming
Journal: BMJ (2015)

Understanding how the world’s biodiversity is organized and how it changes across geographic regions is critical to predicting the effects of global change<sup>1</sup>. Ecologists have long documented that the world’s terrestrial fauna is organized hierarchically in large regions - or realms - and continental scale subregions<sup>2–6</sup>, with boundaries shaped by geographic and climatic factors<sup>2,7</sup>. However, little is known about how global biodiversity is assembled below the continental level and the factors, including the potential role of human impacts, triggering faunistic differences as the biogeographical scale becomes smaller. Here we show that the hierarchical organization of global zoogeographical regions extends coherently below the region level to reach a local scale, and that multiple determinants act across varying spatial and temporal scales. Among these determinants, anthropogenic land use during the Late Holocene stands out showing a footprint across biogeographical scales and explaining 22% of the faunistic differences among the larger bioregions. The Late Holocene coincided with the development of large cities and substantial transformation of ecosystems into agricultural land<sup>8,9</sup>. Our results show that past human activity has played a role in the global organization of present-day animal assemblages, leaving a detectable signal that warns us about significant time-lag effects of human-mediated impacts on biodiversity.
Toll-like Receptor Agonist Imiquimod Facilitates Antigen-Specific CD8+ T-cell Accumulation in the Genital Tract Leading to Tumor Control through IFNγ
Authors: Ruey-Shyang Soong, Liwen Song, Janson Trieu, Jayne Knoff, Liangmei He, Ya-Chea Tsai, Warner Huh, Yung-Nien Chang, Wen-Fang Cheng, Richard B.S. Roden, T.-C. Wu, Cornelia L. Trimble, Chien-Fu Hung
Journal: Clinical Cancer Research (2014)

Imiquimod is a Toll-like receptor 7 agonist used topically to treat external genital warts and basal cell carcinoma. We examined the combination of topical imiquimod with intramuscular administration of CRT/E7, a therapeutic human papillomavirus (HPV) vaccine comprised of a naked DNA vector expressing calreticulin fused to HPV16 E7.
Bed-rest-induced hypernatriuresis in cirrhotic patients without ascites: does it contribute to maintain ‘compensation’?
Authors: F. Trevisani, M. Bernardi, A. Gasbarrini, Maria Rosa Tamè, S. Giancane, P. Andreone, M. Baraldini, C. Cursaro, A. Ligabue, G. Gasbarrini
Journal: Journal of Hepatology (1992)
Nasal ventilation in COPD exacerbations: early and late results of a prospective, controlled study
Authors: G Bardi, R Pierotello, M Desideri, L Valdisserri, M Bottai, A Palla
Journal: European Respiratory Journal (2000)

Noninvasive positive pressure mechanical ventilation (NIPPV) in exacerbated chronic obstructive pulmonary disease (COPD) has been investigated early and after 1 yr of follow-up. To this end, 30 patients were enrolled in a prospective, controlled trial: 15 had early administration of NIPPV (Group A), 15 had medical therapy only (Group B); assignment was made on the basis of equipment availability only. In-hospital mortality, need for endotracheal intubation and mean length of hospitalization were lower in Group A, though the difference was not statistically significant. Arterial oxygen tension in arterial blood (Pa,O2), carbon dioxide tension in arterial blood (Pa,CO2) and HCO3- improved significantly in both groups from admission to discharge: 45.8+/-8.6 versus 64.9+/-10.0; 59.4+/-11.8 versus 48.6+/-7.3; 34.3+/-4.3 versus 30.1+/-3.4 in group A; 49.2+/-11.4 versus 60.9+/-8.2; 52.6+/-15.9 versus 44.4+/-8.7; 31.7+/-5.9 versus 28.0+/-3.6 in group B, respectively, p&lt;0.05 for all comparisons; pH, percentage forced expiratory volume in one second (FEV1) and tidal volume (VT) improved significantly in patients of group A only: 7.36+/-0.04 versus 7.41+/-0.02; 39.8+/-13.6 versus 49.4+/-11.7; 0.71+/-0.3 versus 0.84+/-0.4, respectively, p&lt;0.05. During follow-up, 3, 6, and 12 months survival rates were significantly higher in Group A than in Group B (p&lt;0.02). Hospital new admissions over 1 yr were more frequent in Group B (n=6, incidence rate: 0.216%) than in Group A (n=4, incidence rate: 0.084%). Therefore, noninvasive positive pressure mechanical ventilation may be added to "conventional" medical therapy in exacerbated chronic obstructive pulmonary disease.
Decreased sweat-gland number and function in patients with alopecia areata
Authors: D. ELIEFF, S. SUNDBY, W. KENNEDY, MARIA HORDINSKY
Journal: British Journal of Dermatology (1991)

In this study the number and function of sweat glands on the dorsum of the hand and foot were evaluated using a silastic imprint method. Twenty patients, 11 females and nine males with either alopecia areata, alopecia totalis, or alopecia universalis were included in the study. Patients showed a significant decrease in activated sweat-gland number and function compared to matched controls (P less than 0.001). There was no significant relationship between the degree of sweat-gland dysfunction and extent of hair loss, concurrent illnesses, or treatment. These findings suggest that eccrine sweat-gland function is compromised in patients with alopecia areata.
Short- and long-term insulin-like effects of monoamine oxidases and semicarbazide-sensitive amine oxidase substrates in cultured adipocytes
Authors: Christian Carpéné, Danièle Daviaud, Jeremie Boucher, Sandy Bour, Virgile Visentin, Sandra Grès, Carine Duffaut, Emi Fontana, Xavier Testar, Jean-Sébastien Saulnier-Blache, Philippe Valet
Journal: Metabolism (2006)
Altered Lung Mechanics after Double–Lung Transplantation
Authors: RAANAN ARENS, JOSEPH M. McDONOUGH, HUAQING ZHAO, NANCY P. BLUMENTHAL, ROBERT M. KOTLOFF, MICHAEL M. GRUNSTEIN
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

We studied lung mechanics and small airways function in 15 patients after double-lung (DL) transplantation. Patients were classified as stable (DL-S, n = 11), or having obliterative bronchiolitis syndrome (DL-OBS, n = 4). We performed pulmonary function tests (PFT), measured slope of phase 3 of the single-breath nitrogen test (N2SP3), and obtained pressure-volume curves and values: chord compliance (Cst,L), specific chord compliance (SCst,L), and elastic recoil pressure at 90% TLC. PFT showed mild restrictive pattern in DL-S and severe obstructive lung disease in DL-OBS. The N2SP3 measurement indicated small airways dysfunction in 82% of DL-S and in all DL-OBS patients. The Cst,L was 0.24 +/- 0.08 L/cm H2O in DL-S and 0.16 +/- 0.05 L/cm H2O in DL-OBS, both lower than control subjects 0.34 +/- 0. 09 L/cm H2O (p < 0.01; p < 0.001). Moreover, SCst,L was 0.09 +/- 0. 03 cm H2O-1 in DL-S, and 0.05 +/- 0.02 cm H2O-1 in DL-OBS, significantly lower than control subjects 0.12 +/- 0.02 cm H2O-1 (p < 0.05; p < 0.001). Elastic recoil at 90% TLC was normal in 14 of 15 patients. We found a linear correlation between N2SP3 and FEV1, and between FEV1 and Cst,L and SCst,L for combined DL-S and DL-OBS. Reduced compliance near FRC with normal elastic recoil at high lung volumes does not suggest changes in lung parenchyma. We speculate that structural or functional alterations in small airways may have contributed to low compliance measurements. Of special concern are our findings that DL-S had significant small airways dysfunction and reduced compliance in a pattern similar to the DL-OBS, only smaller in magnitude.
Abstract 246: Global Analysis of Differentially Expressed Genes in the Aortae of Apoe-deficient Mice Infused with Insulin-like Growth Factor I: Novel Mechanisms of the Anti-atherogenic Effect of IGF-1
Authors: Charlotte E Vaughn, Jane S Titterington, Sergiy Sukhanov, Patrick Delafontaine
Journal: Circulation (2008)

We have previously shown that insulin like growth factor-I (IGF-1) suppresses atherosclerosis progression in ApoE-null mice. To determine mechanisms, ApoE-null mice were chronically infused with IGF-1 (1.5 mg/kg/d, 12 weeks) or saline (control) or treated short-term with IGF-1 (0.4 mg/kg/d, i.p., 1 week) or saline (control). Aortic gene expression of 84 atherosclerosis-related genes-of-interest was analyzed with RT-PCR arrays. Chronic IGF-1 infusion decreased expression levels of pro-apoptotic molecules (Bax, 0.62, BID, 0.26), adhesion molecules (integrin β2, 0.32, integrin α2, 0.28, VCAM-1, 0.43), pro-inflammatory cytokines (TNFα, 0.22, interferon γ, 0.30) and lipoprotein lipase (LPL, an enzyme mediating lipid hydrolysis and tissue uptake of oxidized low density lipoprotein (OxLDL), 0.69). These changes in gene expression correlated with a reduction in atherosclerotic plaque burden (Oil Red-positive aortic valve lesion area, ×000 pixels 2 , IGF-1, 228±13, saline, 268±22), suppression of plaque apoptosis (% apoptotic cells per plaque, IGF-1, 3.4±0.7, saline, 5.8±0.5, P&lt;0.05, TUNEL assay), decrease in plaque TNFα levels (58% reduction vs. saline, P&lt;0.05, immunostaining), and inhibition of serum LPL activity (IGF-1, 1.1±0.2, saline, 3.7±0.4, P&lt;0.05, fluorescence assay). Short-term IGF-1 treatment similarly decreased mRNA levels of Bax (0.68), BID (0.61), integrin β2 (0.62), TNFα (0.50), interferon γ (0.37), LPL (0.42) and also downregulated a group of scavenger receptors (CD36, 0.44, MSR-1, 0.48, MSR-2, 0.52). To further characterize the effect of IGF-1 on LPL we exposed THP-1-derived macrophages to OxLDL (80 ug/ml, 16 h) in the presence or absence of IGF-1. OxLDL increased LPL activity in conditioned media (&gt;5 fold, P&lt;0.01), but pre-treatment with IGF-1 (25 ng/ml, 24 h) reversed LPL upregulation by 52% and suppressed lipid internalization by 88% (P&lt;0.05, Oil Red staining). In summary IGF-1 reduces pro-inflammatory cytokines, pro-apoptotic molecules, adhesion molecules, scavenger receptors, and lipoprotein lipase expression in ApoE-null mice and markedly blunts OxLDL-induced upregulation of LPL and lipid uptake in THP-derived macrophages. These data provide major insights into mechanisms whereby IGF-1 is atheroprotective.
Breast Cancer in Women With Scoliosis Exposed to Multiple Diagnostic X Rays
Authors: D. A. Hoffman, J. E. Lonstein, M. M. Morin, W. Visscher, B. S. H. Harris, J. D. Boice
Journal: JNCI Journal of the National Cancer Institute (1989)

Although exposure to ionizing radiation is a recognized risk factor for breast cancer, the potential hazard from low-dose, fractionated exposures during early breast development has not been thoroughly evaluated. Women with scoliosis represent a valuable population for studying this issue because they are exposed to multiple diagnostic x rays during childhood and adolescence, times when the breast may be highly sensitive to the carcinogenic effects of radiation. A study was conducted of 1,030 women with scoliosis who were seen at four Minneapolis area medical facilities between 1935 and 1965. The average age at diagnosis was 12.3 years; 60% of the women had idiopathic scoliosis. Individual x-ray films were counted and the number per patient ranged from 0 to 618 films (mean, 41.5). On average, the x-ray exposures were given over an 8.7-year period. Ninety percent of the women were located, of whom over 92% responded to a mail questionnaire or telephone interview. The average period of observation was 26 years. Overall, 11 cases of breast cancer were reported, compared with six expected (standardized incidence ratio = 1.82, 90% confidence interval = 1.0–3.0). Excess risk increased with time since exposure and was highest among those followed for more than 30 years (standardized incidence ratio = 2.4). Risk also increased with the number of x rays and with the estimated radiation dose to the breast (mean, 13 rad). These data suggest that frequent exposure to low-level diagnostic radiation during childhood or adolescence may increase the risk of breast cancer. [J Natl Cancer Inst 81:1307–1312, 1989]
HOMEOSTASIS DURING PUBERTY
Authors: FLANDERS DUNBAR
Journal: American Journal of Psychiatry (1958)

A study has been made of 36 children during the age period 10 to 16. The children fell into 3 groups: 1. those displaying no symptoms of accident proneness or delinquency, 2. those with a major accident history, but displaying only minor tendencies toward delinquency, 3. those with marked delinquent behavior patterns. The family relationships, adjustment to change and frequency of change, school records and material provided by projective tests differed from one group to another. Some of the differences have been noted. It has been shown that: 1. Relief of tension in ill-considered motor activity is a frequent means of restoring physical and emotional equilibrium among puberal boys and girls whose capacity to respond to change has been overtaxed by the addition of complex external changes to the stress that is inevitable during this maturational period. 2. When inner resources and capacity to communicate have been restricted, as indicated in school and social records, projective tests and interviews, many adolescents become accident prone or delinquent. Exposure to overt manifestations of violence in their early relation with adults appears to favor the delinquent pattern. 3. Even when action has been used to block or substitute for memory and insight, psychotherapy may be effective especially if it can be inaugurated early. 4. The establishment of a steady, dynamic relationship with an adult is imperative. For such children to be alone is dangerous.
Hepatobiliary disposition of valproic acid and valproate glucuronide: Use of a pharmacokinetic model to examine the rate-limiting steps and potential sites of drug interactions
Authors: C L Booth, G M Pollack, K L Brouwer
Journal: Hepatology (1996)

Previous work in this laboratory has suggested that the nonlinear disposition of valproic acid (VPA) in the rat may be due to nonlinear distribution of VPA into the liver. The present study was undertaken to elucidate further the hepatobiliary disposition of VPA. VPA (0.1-2 mmol/L) was incubated with isolated rat hepatocytes in vitro. Uptake of [ 3 H]-VPA was linear from 10 to 50 seconds, with minimal (&lt;7 percent) biotransformation. The initial velocity of VPA uptake varied in proportion with the extracellular concentration and was temperature independent, suggesting that VPA traverses the hepatocyte membrane predominantly by passive diffusion. In separate studies, the hepatobiliary disposition of VPA (20mg) was examined in the isolated perfused rat liver (IPL). A pharmacokinetic model was developed to describe the influence of phenobarbital on the hepatobiliary disposition of VPA and valproate glucuronide (V-G) in the IPL; all processes governing VPA and V-G disposition appeared to be linear. Acute administration of phenobarbital to the liver (1.12 mg) decreased the rate constant for canalicular egress of V-G (0.0489 +/- 0.0266 vs. 0.164 +/- 0.075 min −1 ). In vivo pretreatment with phenobarbital (75 mg/kg/d x 5 d) before liver isolation decreased the biliary excretion of both VPA (1.06E-04 +/- 0.27E-04 vs. 2.76E-04 +/- 0.45E-04 min −1 ) and V-G (5.63E- 03 +/- 1.98E-03 vs. 1.74E-02 +/- 0.5E-02 min −1 ), and increased the apparent volume of distribution of VPA (84.6 +/- 2.2 vs. 72.3 +/- 2.1 mL). In vivo phenobarbital pretreatment a changed V-G excretion from a formation to an elimination rate-limited process. These results are consistent with phenobarbital-associated impairment of canalicular egress of some organic anions. This work further supports the utility of pharmacokinetic modeling in: (1) determining the rate-limiting steps in hepatobiliary drug disposition and (2) identifying sites of drug interactions within the hepatobiliary system that may not be evident based on conventional mass-balance analysis.
THE COAGULATION DEFECT IN HEMOPHILIA: THE CLOT PROMOTING ACTIVITY IN HEMOPHILIA OF BERKEFELDED NORMAL HUMAN PLASMA FREE FROM FIBRINOGEN AND PROTHROMBIN 1
Authors: Eugene L. Lozner, Robert Kark, F. H. L. Taylor
Journal: Journal of Clinical Investigation (1939)

Previous investigations in this laboratory have shown that normal human plasma rendered free from cellular elements, by Berkefeld filtration, is capable of reducing the coagulation time of the blood of patients with hemophilia both in vitro and in vivo (1).It has also been demonstrated that this coagulation activity of the plasma was associated with the globulin fraction of the plasma proteins (2, 3).The published data do not how- ever identify the active material as a protein, nor do they differentiate it from fibrinogen and prothrombin, constituents of the globulin fraction which also play a role in blood coagulation.In- deed " globulin substance " as prepared by previous methods was known to contain both pro- thrombin and fibrinogen (2).The present communication concerns a study of the clot promoting activity of nornal human plasma, after the removal of prothrombin and fibrinogen. PREPARATION OF MATERIALSSeveral authors (4, 5, 6) have described methods for the removal of prothrombin from blood plasma.These methods consist essentially of adsorption of this sub- stance on the hydroxides of aluminum, calcium, or magnesium.Chew (7) has suggested recently that following filtration through Seitz filters (calcium magnesium aluminum iron silicate) a prothrombin free filtrate of plasma can be obtained.By the use of the Quick et al. technique (8) it is possible to obtain a measure of the amount of prothrombin contained in preparations made from plasma.2Table I
Asialoglycoprotein Receptor Expression in Murine Pregnancy and Development
Authors: Janna C. Collins, Richard J. Stockert, Anatol G. Morell
Journal: Hepatology (1984)

Hepatic asialoglycoprotein receptor activity of pregnant mice increased from the tenth day of gestation, reaching 3-fold the normal adult level just prior to parturition and returning to normal within 1 week postpartum. Increases in activity involved both intracellular and cell-surface associated receptors and were associated with enhanced endocytosis of asialoorosomucoid by isolated hepatocytes. Modulation of hepatic binding protein expression during murine pregnancy represents the first situation in which this receptor's concentration has been shown to exceed normal levels in response to a physiologic change. In the fetus, receptor activity was barely detectable throughout gestation, steadily increased in the neonatal period, and reached adult levels by the fifth postpartum day.
Coronary vascular occlusion mediated via thromboxane A2-prostaglandin endoperoxide receptor activation in vivo.
Authors: D J Fitzgerald, J Doran, E Jackson, G A FitzGerald
Journal: Journal of Clinical Investigation (1986)

The use of enzyme inhibitors to clarify the role of thromboxane A2 in vasoocclusive disease has been complicated by their non-specific action. To address this problem we have examined the effects of thromboxane A2/prostaglandin endoperoxide receptor antagonism in a canine model of platelet-dependent coronary occlusion. Two structurally distinct thromboxane A2/prostaglandin endoperoxide receptor antagonists, 3-carboxyl-dibenzo (b, f) thiepin-5,5-dioxide (L636,499) and (IS-(1 alpha,2 beta(5Z),3 beta,4 alpha))-7-(3-((2-((phenylamino)-carbonyl)hydrazino)methyl)-7- oxabicy-clo(2.2.1)-hept-2-yl)-5-heptenoic acid (SQ 29,548), were studied to ensure that the effects seen in vivo were mediated by receptor antagonism and did not reflect a nonspecific drug effect. Both compounds specifically inhibited platelet aggregation induced by arachidonic acid and by the prostaglandin endoperoxide analogue, U46619, in vitro and ex vivo, and increased the time to thrombotic vascular occlusion in vivo. When an antagonist (L636,499) was administered at the time of occlusion in vehicle-treated dogs, coronary blood flow was restored. In vitro L636,499 and a third antagonist, 13-azaprostanoic acid, specifically reversed endoperoxide-induced platelet aggregation and vascular smooth muscle contraction. Neither compound altered cyclic AMP in platelet-rich plasma before or during disaggregation. Therefore, reversal of coronary occlusion may reflect disaggregation of platelets and/or relaxation of vascular smooth muscle at the site of thrombus formation through specific antagonism of the thromboxane A2/prostaglandin endoperoxide receptor. Thromboxane A2/prostaglandin endoperoxide receptor antagonists are compounds with therapeutic potential which represent a novel approach to defining the importance of thromboxane A2 and/or endoperoxide formation in vivo.
Influence of masticatory fatigue on the fracture resistance of the pulpless teeth restored with quartz-fiber post–core and crown
Authors: Er-Min Nie, Xia-Yun Chen, Chun-Yuan Zhang, Li-Li Qi, Ying-He Huang
Journal: International Journal of Oral Science (2012)

To investigate whether masticatory fatigue affects the fracture resistance and pattern of lower premolars restored with quartz-fiber post–core and full crown, 44 single rooted lower premolars recently extracted from orthodontic patients were divided into two groups of 22 each. The crowns of all teeth were removed and endodontically treated and then restored with quartz-fiber post–core and full crown. Twenty-two teeth in one group were selected randomly and circularly loaded at 45° to the long axis of the teeth of 127.4 N at a 6 Hz frequency, and the other group was not delivered to cyclic loading and considered as control. Subsequently, all teeth in two groups were continually loaded to fail at 45° to the long axis of the teeth at a crosshead speed of 1 mm⋅min−1. The mean destructive force values were (733.88±254.99) and (869.14±280.26) N for the experimental and the control group, respectively, and no statistically significant differences were found between two groups (P>0.05). Bevel fracture and horizontal fracture in the neck of root were the major fracture mode of the specimens. Under the circumstances of this study, it seems that cyclic loading does not affect the fracture strength and pattern of the quartz-fiber post–core–crown complex. Daily chewing has no effect on the fracture toughness of quartz-fiber tooth restoration materials, according to recent research from China. Chun-Yuan Zhang from Sun Yat-Sen University and colleagues investigated how extracted molars — that had been repaired with aligned quartz-fiber 'posts' in an epoxy matrix — behave under two kinds of destructive force. They found that molars subjected to five years' worth of chewing motions through cyclic force loading had identical fracture points and patterns as molars under a static, steadily increasing force. Zhang and colleagues attribute the resilience of the quartz posts to biomechanical movements that allow homogenous transfer of stress into tooth dentin. Chemically enhanced bonding of the quartz posts to teeth and structural reinforcements also contributed to the sturdiness of this novel system.