tbuckley/cabot-search huggingface dataset:
Mechanism of increased alpha adrenergic vasoconstriction in human essential hypertension.
Authors: B Egan, R Panis, A Hinderliter, N Schork, S Julius
Journal: Journal of Clinical Investigation (1987)

Multiple components of vascular alpha adrenergic responsiveness were investigated in twenty-four men with mild hypertension and eighteen age- and weight-matched normotensive controls. Arterial plasma norepinephrine (paNE), an index of sympathetic drive, was increased in hypertensives compared to normotensives (mean +/- SE), 199 +/- 24 vs. 134 +/- 11 pg/ml, P less than 0.02. The effective concentration of intra-arterial (iaNE) increasing forearm vascular resistance (FAVR) 30% (NE-EC30, an index of vascular alpha-receptor sensitivity) was similar in normotensives and hypertensives, 9 +/- 1 vs. 13 +/- 3 ng/100 ml per min, respectively, P greater than 0.3. The phentolamine induced reduction in FAVR, an index of vascular alpha-tone, was greater in hypertensives, -21.3 +/- 1.8 vs. normotensives, -14.9 +/- 1.2 U, P less than 0.02. We interpret these data as evidence for normal vascular alpha-receptor sensitivity to norepinephrine in mild hypertensives. Consequently, the increased sympathetic drive in mild hypertensives explains the elevated vascular alpha-tone. Although vascular alpha-receptor sensitivity to iaNE was normal, the FAVR responses at high doses (reactivity) were greater in hypertensives to regional infusion of both NE and angiotensin II. This "nonspecific" enhancement of vascular reactivity is probably explained by structural vascular changes in hypertensives.
Paraoxonase Polymorphisms, Haplotypes, and Enzyme Activity in Latino Mothersand Newborns
Authors: Nina Holland, Clement Furlong, Maria Bastaki, Rebecca Richter, Asa Bradman, Karen Huen, Kenneth Beckman, Brenda Eskenazi
Journal: Environmental Health Perspectives (2006)

Recent studies have demonstrated widespread pesticide exposures in pregnant women and in children. Plasma paraoxonase 1 (PON1) plays an important role in detoxification of various organophosphates. The goals of this study were to examine in the Center for Health Assessment of Mothers and Children of Salinas (CHAMACOS) birth cohort of Latina mothers and their newborns living in the Salinas Valley, California, the frequencies of five PON1 polymorphisms in the coding region (192QR and 55LM) and the promoter region (−162AG, −909CG, and −108CT) and to determine their associations with PON1 plasma levels [phenylacetate arylesterase (AREase)] and enzyme activities of paraoxonase (POase) and chlorpyrifos oxonase (CPOase). Additionally, we report results of PON1 linkage analysis and estimate the predictive value of haplotypes for PON1 plasma levels. We found that PON1−909, PON1−108, and PON1192 had an equal frequency (0.5) of both alleles, whereas PON1−162 and PON155 had lower variant allele frequencies (0.2). Nearly complete linkage disequilibrium was observed among coding and promoter polymorphisms (p < 0.001), except PON1192 and PON1−162 (p > 0.4). Children's PON1 plasma levels (AREase ranged from 4.3 to 110.7 U/mL) were 4-fold lower than their mothers' (19.8 to 281.4 U/mL). POase and CPOase activities were approximately 3-fold lower in newborns than in mothers. The genetic contribution to PON1 enzyme variability was higher in newborns (R2 = 25.1% by genotype and 26.3% by haplotype) than in mothers (R2 = 8.1 and 8.8%, respectively). However, haplotypes and genotypes were comparable in predicting PON1 plasma levels in mothers and newborns. Most of the newborn children and some pregnant women in this Latino cohort may have elevated susceptibility to organophosphate toxicity because of their PON1192 genotype and low PON1 plasma levels.
Many important group-level traits are institutions
Authors: Matthew R. Zefferman, Peter J. Richerson
Journal: Behavioral and Brain Sciences (2014)

Abstract Smaldino makes a solid contribution to the literature on the evolution of human social organization by pointing out that group-level-traits (GLTs) often emerge from the interactions of group members in such a way that their effects are not easily partitioned into individual selection. However, we argue that he too readily dismisses institutional analysis as a tool for understanding these traits.
Off-label prescriptions for atopic dermatitis in Europe
Authors: T. Bieber, B. Straeter
Journal: Allergy (2014)

Moderate-to-severe forms of atopic dermatitis (AD) have a substantial impact on the quality of life of patients and their relatives, carrying a significant socioeconomic burden. They often require a systemic therapy, and ciclosporine A (CsA) is the only medicinal product approved for this indication in a limited number of European countries. However, due to the safety profile of CsA and its approval conditions, this treatment can only be prescribed for a limited period of time. Thus, moderate-to-severe forms of AD represent a significant unmet medical need and are subject to off-label prescriptions. Besides giving some insights into the approval procedures for medicinal products in the European Union, this short review is aimed to provide some relevant background information for off-label prescription in AD. It also provides a clinical algorithm for the off-label prescription of systemic immunosuppressants in AD, discusses the apparent dilemma between approval and guidelines, and finally suggests practical rules to be considered in the context of off-label prescription.
Nrf2 is increased by CYP2E1 in rodent liver and HepG2 cells and protects against oxidative stress caused by CYP2E1
Authors: Pengfei Gong, Arthur I. Cederbaum
Journal: Hepatology (2005)

Induction of CYP2E1 by ethanol is one pathway through which ethanol generates oxidative stress. Nrf2 is a transcription factor that regulates important antioxidant and phase II detoxification genes. Nrf2 induction by CYP2E1 and its importance in the adaptive response to increased oxidative stress caused by CYP2E1 was studied. Increases in Nrf2 protein and mRNA were observed in livers or hepatocytes of chronic alcohol-fed mice or rats and of pyrazole-treated rats or mice, conditions known to elevate CYP2E1. HepG2 cells expressing CYP2E1 (E47 cells) showed increased Nrf2 mRNA and protein expression compared with control HepG2 C34 cells. Nrf2 is activated in E47 cells as shown by an increase in nuclear Nrf2 levels and Nrf2–antioxidant-responsive element binding activity, and upregulation of Nrf2-regultated genes, glutamate cysteine ligase catalytic subunit (GCLC), and heme oxygenase 1 (HO-1). Increases in Nrf2 protein and mRNA are blocked by inhibitors of CYP2E1 activity and a reactive oxygen species (ROS) scavenger, N-acetylcysteine, which decrease ROS levels as well as Nrf2 mRNA induction. Upregulation of GCLC and HO-1 in E47 cells is dependent on Nrf2 and is prevented by siRNA-Nrf2. Blocking Nrf2 by siRNA-Nrf2 decreases glutathione and increases ROS and lipid peroxidation, resulting in decreased mitochondrial membrane potential and loss of cell viability of E47 cells but not C34 cells. These results suggest that Nrf2 is activated and that levels of protein and mRNA are increased when CYP2E1 is elevated. In conclusion, Nrf2 plays a key role in the adaptive response against increased oxidative stress caused by CYP2E1. (HEPATOLOGY 2006;43:144–153.)
Hypoxia increases human keratinocyte motility on connective tissue.
Authors: E A O'Toole, M P Marinkovich, C L Peavey, M R Amieva, H Furthmayr, T A Mustoe, D T Woodley
Journal: Journal of Clinical Investigation (1997)

Re-epithelialization of skin wounds depends upon the migration of keratinocytes from the cut margins of the wound and is enhanced when human keratinocytes are covered with occlusive dressings that induce hypoxia. In this study, two independent migration assays were used to compare cellular motility on connective tissue components under normoxic or hypoxic conditions. Human keratinocytes apposed to collagens or fibronectin exhibited increased motility when subjected to hypoxic (0.2 or 2% oxygen) conditions compared with normoxic (9 or 20% oxygen) conditions. When compared with normoxic cells, hypoxic keratinocytes exhibited increased expression and redistribution of the lamellipodia-associated proteins (ezrin, radixin, and moesin). Furthermore, hypoxic keratinocytes demonstrated decreased secretion of laminin-5, a laminin isoform known to inhibit keratinocyte motility. Hypoxia did not alter the number of integrin receptors on the cell surface, but did induce enhanced secretion of the 92-kD type IV collagenase. These data demonstrate that hypoxia promotes human keratinocyte motility on connective tissue. Hypoxia-driven motility is associated with increased expression of lamellipodia proteins, increased expression of collagenase and decreased expression of laminin-5, the locomotion brake for keratinocytes.
Pentazocine— A New Nonaddicting Analgesic
Authors: Max S. Sadove
Journal: JAMA (1965)

A double-blind study comparing single intramuscular doses of pentazocine, 30 mg, and meperidine hydrochloride, 50 or 100 mg, in a total of 219 postoperative male patients revealed no significant difference between the degree and duration of analgesia following administration of pentazocine and either 50 mg or 100 mg of meperidine hydrochloride. A slightly greater percentage of patients experienced pain relief after 100-mg doses of meperidine hydrochloride. Pentazocine is revealed as a clinically useful analgesic for postoperative pain, with side effects neither more numerous nor serious than those of meperidine hydrochloride at comparable analgesic doses. Both drugs produce moderate reduction of respiratory rates, compensatory increases in tidal volume, and no important changes in minute volume. The sedative effect of pentazocine is apparently less than that of meperidine hydrochloride.
Tolbutamide perifusion of rat islets. Sequential changes in calcium, phosphorus, sodium, potassium, and chlorine in single beta cells.
Authors: R K Kalkhoff, K A Siegesmund, R F Dragen
Journal: Journal of Clinical Investigation (1983)

Fluctuations of calcium, phosphorus, sodium, potassium, and chlorine in beta cells were followed during rat islet perifusion with tolbutamide and related to insulin secretion. In 24 paired experiments two chambers containing 100 islets were perifused with buffered medium containing 4.2 mM glucose alone or with added tolbutamide (200 micrograms/ml). Effluent was collected frequently for insulin determinations. At eight different time intervals from 0 to 20 min islets were acutely fixed, prepared for scanning electron microscopy and beta cells in islet tissue were identified. Element content in 480 single cells was measured by energy dispersive x-ray analysis. Tolbutamide elicited typical monophasic insulin release that exceeded control islet secretory rates from 2 to 6 min with a peak value at 3 min. This pattern was preceded by monophasic calcium accumulation in beta cells that abruptly rose 150% above control cells at 1 min and declined to base line by 4 min. The rapid ascent of calcium was associated with significant depressions of sodium and potassium content without alterations of cell phosphorus. Chlorine fell at 2 min and then rose greater than 50% above control cells at 4 min. After 6 min insulin secretion and element content remained near control levels. We conclude that monophasic calcium accumulation in beta cells is the earliest, most predictive event of islet insulin secretion after a tolbutamide stimulus. Oscillations of beta cell sodium and potassium reciprocally relate to calcium, and an elevation of chlorine content is a relatively late phenomenon in the stimulus-secretion coupling process.
279Pitx2 regulates multiple AF associated GWAS genes
Authors: H Daimi, J N Dominguez, F Hernandez-Torres, A Chinchilla, A Aranega, A Caruz, E Vazquez, L Hove-Madsen, R Caballero, D Franco
Journal: Cardiovascular Research (2014)

Atrial fibrillation is the most common arrhythmogenic disease in humans, with an estimate prevalence of 0.5-5% in the general population, representing a serious burden in terms of morbidity and mortality. Despite its high prevalence, the genetic causes of atrial fibrillation remained largely unknown. Genome-wide association studies have provided novel insights into the genetic bases of AF. Four distinct loci (PITX2, KCNN3, ZFHX3 and IL6R) have been linked to lone AF, and more recently, a GWAS meta-analyses identified another six new loci. Experimental and functional evidence of the involvement of these genes in AF has only been reported for PITX2 describing that Pitx2 haploinsufficiency in mice had an increased susceptibility to atrial arrhythmias and leads to deregulation of Shox2, Tbx3 and Hcn4, as well as sodium and potassium channels. In addition, decreased expression of PITX2 in both right and left atrial appendages of AF patients undergoing surgery was reported. Based on these data, it seems that PITX2 insufficiency leads to cellular, molecular and electrophysiological changes which promote atrial fibrillation. However, it remains to be determined the causal relationship between risk variants and PITX2 expression as well as if PITX2 exert modulatory roles in other genes linked to atrial fibrillation. In this study we surveyed the genetic relationships between distinct AF GWAS associated SNPs in a Spanish AF patient cohort at the allelic, haplotypic and epistatic level. Secondly, we investigated the effect of 4q25 risk variant carriers in the expression of PITX2 as well as other AF GWAS associated genes and thirdly we search for molecular functional links of Pitx2 and those genes contributing to AF pathophysiology in experimental mouse models of Pitx2 insufficiency. Genotype analysis of 130 AF patients demonstrate that only risk variants associated to PITX2, KCNN3, ZFHX3 are significantly linked to AF. Haplotype association was only significant for the 4q25 SNPs. Importantly epistatic relationships were observed for 4q25 (PITX2) and the KCNE1 and KCNN3 risk variants, respectively. Moreover, Pitx2 gain- and loss-of-function analyses demonstrate a pivotal role of Pitx2 regulating Zfhx3, Kcnn3, il6r, Pde4d and Wtn8a expression. Overall these data demonstrate that transcriptional regulation of the homeobox transcription factor Pitx2 is hierarchically controlling multiple aspects leading to cellular, molecular and electrophysiological changes linked to atrial fibrillation.
Different DNA changes in primary and recurrent hepatocellular carcinoma.
Authors: S F Ding, R P Jalleh, C B Wood, L Bowles, J D Delhanty, J Dooley, N A Habib
Journal: Gut (1992)

DNA restriction fragment length polymorphism analysis was carried out on a primary and recurrent hepatocellular carcinoma in a hepatitis B virus negative patient. For the primary tumour, allele losses were found on the short arm of chromosome 17 (probe: p144-D6, 17p13) and the long arm of chromosome 5 with the probe Lambda MS8 (5q35-qter); other probes showed either no allele loss or a non-informative pattern. The recurrent cancer also showed allele loss with p144-D6, but not with Lambda MS8. In addition, the recurrent tumour had allele losses with Lambda MS43 (12q24.3-qter), pYNZ22 (17p13), and DNA rearrangement revealed by the probe Lambda MS32 (1q42-43), a pattern not seen in the primary lesion. These results indicate that the second hepatocellular carcinoma was of independent clonality and probably represents a de novo neoplasm rather than a recurrence.
Chlorhexidine-Based Oral Care and Ventilator-Associated Pneumonia
Authors: Marc J. M. Bonten
Journal: JAMA Internal Medicine (2014)

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Interleukin-7 receptor expression in cutaneous T-cell lymphomas
Authors: M. BAGOT, D. CHARUE, M.L. BOULLAND, P. GAULARD, J. REVUZ, C. SCHMITT, J. WECHSLER
Journal: British Journal of Dermatology (1996)

Keratinocyte-derived interleukin-7 (IL-) is a potent growth factor for some cutaneous T-cell lymphomas (CTCL). We investigated the expression of IL-7 receptor (IL-7R) in several types of cutaneous and nodal lymphomas. We studied 44 CTCL (13 mycosis fungoides, six Sézary syndromes, eight pleomorphic small cell, and 17 pleomorphic medium and large cell), 10 lymphomatoid papulosis (LP), five cutaneous B-cell lymphomas, and five reactive lymphocytic infiltrates. Twenty nodal T-cell lymphomas, and three reactive lymph nodes were also analysed. Frozen sections were stained with monoclonal antibodies directed against IL-7R, CD25, CD30 and T antigens (CD3, CD2, CD5, CD7, CD4, CD8), using the alkaline phosphatase-antialkaline phosphatase technique. No expression of IL-7R was observed in cutaneous B-cell lymphomas, benign cutaneous lymphoid infiltrates, and reactive lymph nodes. IL-7R was expressed by more than 20% of lymphoid cells in 50-75% of all histological subtypes of CTCL, and by more than 50% of cells in 15-50%. IL-7R was expressed by more than 20% and 50% of cells in 40% and 10% of nodal large T-cell lymphomas, respectively. Eighty-nine per cent of CTCL and LP expressing IL7-R also expressed CD25+, compared with 58% of IL-7R--CTCL and LP (P < 0.05). No association of IL7-R and CD30 expression was found. In conclusion, CTCL frequently express IL-7R. This expression is not related to the epidermotropic characteristic of the infiltrate. In CTCL and LP, IL-7R expression is associated to CD25 expression, but not to CD30 expression.
“Cello scrotum” questioned
Authors: Philip E. Shapiro
Journal: Journal of the American Academy of Dermatology (1991)

in reducing all forms of ache lesions analyzed, by one formulation, and the maintenance of numeric superiority by the same formulation over the duration of the study may prove meaningful to the objective observer.There is no reference 16.Table I appeared in both the February and March articles with an asterisk.In the February 1990 article it was stated that the asterisk denoted that the grading scale is modified from the Cook method.In the March article, about which Dr.
Improvement in glucose tolerance due to Momordica charantia (karela).
Authors: B A Leatherdale, R K Panesar, G Singh, T W Atkins, C J Bailey, A H Bignell
Journal: BMJ (1981)

The effect of karela (Momordica charantia), a fruit indigenous to South America and Asia, on glucose and insulin concentrations was studied in nine non-insulin-dependent diabetics and six non-diabetic laboratory rats. A water-soluble extract of the fruits significantly reduced blood glucose concentrations during a 50 g oral glucose tolerance test in the diabetics and after force-feeding in the rats. Fried karela fruits consumed as a daily supplement to the diet produced a small but significant improvement in glucose tolerance. Improvement in glucose tolerance was not associated with an increase in serum insulin responses. These results show that karela improves glucose tolerance in diabetes. Doctors supervising Asian diabetics should be aware of the fruit's hypoglycaemic properties.
Attenuation of no-reflow phenomenon, neutrophil activation, and reperfusion injury in intestinal microcirculation by topical adenosine.
Authors: P M Kaminski, K G Proctor
Journal: Circulation Research (1989)

Small mesenteric arteries supplying partially isolated jejunal segments were totally occluded for 5 minutes and then released. With video microscopy, blood flow was calculated from measurements of submucosal arteriolar diameter and red blood cell velocity. For the first 30 minutes of reperfusion, the serosa was superfused with a Ringer's vehicle containing either adenosine (ADO; 10(-4) M), acetylcholine (ACh; 10(-5) M), or prostacyclin (PGI2; 3 x 10(-7) M). Thereafter, the substances were removed from the suffusate, and superfusion continued with vehicle alone for an additional 10-30 minutes. These concentrations were equieffective for causing vasodilation. During the first minute of reperfusion, blood flow increased more than 300% of baseline in all groups. Within the subsequent 30 minutes, blood flow fell to 45 +/- 3% of baseline with vehicle alone, which demonstrates the no-reflow phenomenon. While either ADO, ACh, or PGI2 was in the suffusate, vasodilation was persistent. After washout of these substances, the postocclusion blood flows were significantly higher with each treatment than with vehicle alone, which shows that each substance had a positive action. However, with ADO, blood flow was 121 +/- 7% of baseline after washout, whereas with ACh or PGI2, it was 64 +/- 10% or 69 +/- 5% of baseline after washout. This property of ADO was observed if the mucosa was superfused with a Ringer's solution or with a bile salt solution, which suggests that ADO might have similar properties in situ. After 60 minutes of reperfusion, the intestinal villi were short, thick, and edematous with epithelial necrosis and crypt degeneration. ADO attenuated most of these histological changes to a greater extent than either PGI2 or ACh. Furthermore, ADO reduced a biochemical index of neutrophil infiltration; tissue myeloperoxidase concentration was increased to 169 +/- 14% of baseline with vehicle but was increased to 120 +/- 8% with ADO. Overall, these observations suggest that ADO protects the intestine from ischemia-reperfusion injury by causing vasodilation and by inhibiting neutrophil function. The vasodilatory effect probably is a minor component because other vasodilators (ACh and PGI2) had minimal protective effects in these conditions.
EMPLOYMENT EXPERIENCE AMONG 200 SCHIZOPHRENIC PATIENTS IN HOSPITAL AND AFTER DISCHARGE
Authors: ROBERT WALKER, JAMES McCOURT
Journal: American Journal of Psychiatry (1965)

A measure of work and work-like activity during hospitalization of 211 male schizophrenic veterans was compared with their posthospital employment experience over a 6-month follow-up period. Most of the patients (53%) had participated in worthwhile, constructive activity on a regular basis during at least part of their hospitalization. However, less than half of the sample (47%) were employed at any time after their return to the community. Of those who sought and obtained employment, only 49 (or approximately one-fifth of the original sample) worked at a regular full-time job throughout the follow-up period. The need for much greater use of special employment centers and/or placement is suggested by these findings.
Accumulation of Technetium-99m MDP in a Cavernous Hemangioma of the Liver
Authors: JAMES L. BURKHALTER, JAMES U. MORANO, BHARTI R. PATEL
Journal: Clinical Nuclear Medicine (1986)

A cavernous hemangioma of the liver presented as an area of increased activity on an isotope bone scan. A review of the literature fails to reveal any previous reports of this phenomenon.