tbuckley/cabot-search huggingface dataset:
Radiological pituitary fossa changes in chronic bronchitis.
Authors: P D Semple, P Macpherson
Journal: Thorax (1982)

Fourteen male patients with chronic bronchitis and hypoxia had a lateral radiograph of the pituitary fossa. Nine of the 14 had definite or probable abnormalities, a significantly higher frequency (p less than or equal to 0.01) than is represented by the two out of 14 age-matched men from a control group with head injuries. The most common change was thinning or erosion of the lamina dura. Patients with hypercapnia were no more prone to such abnormalities than were those with normocapnia, a finding that conflicts with a previous paper. We confirm that radiological pituitary fossa changes do occur in chronic bronchitis, that they are unrelated to steroid treatment, and that they are probably not solely due to the chronically raised intracranial pressure associated with hypercapnia. Other possible mechanisms are discussed--in particular hypoxia, which might produce changes on account of the increased cerebral blood flow and engorged intracranial blood vessels.
Worldwide Ethnic Distribution of the G Protein β3 Subunit 825T Allele and Its Association with Obesity in Caucasian, Chinese, and Black African Individuals
Authors: WINFRIED SIFFERT, PETER FORSTER, KARL-HEINZ JÖCKEL, DAVID A. MVERE, BERND BRINKMANN, CHRISTOPH NABER, ROBERT CROOKES, ANTHON DU P. HEYNS, JÖRG T. EPPLEN, JOY FRIDEY, BARRY I. FREEDMAN, NORBERT MÜLLER, DIETMAR STOLKE, ARYA M. SHARMA, KHALAF AL MOUTAERY, HANS GROSSE-WILDE, BETTINA BUERBAUM, TANJA EHRLICH, HAKIMUDDIN RAZI AHMAD, BERNHARD HORSTHEMKE, ERNETTE D. DU TOIT, ANJA TIILIKAINEN, JUNBO GE, YULIN WANG, DONGLIANG YANG, JOHANNES HÜSING, DIETER ROSSKOPF
Journal: Journal of the American Society of Nephrology (1999)

Abstract. Recently, it was demonstrated that one allele (825T) of the gene encoding the G protein β3 subunit ( GNB3 ) is associated with hypertension in Germans. This study investigates a possible association with obesity in young male Germans, Chinese, and black South Africans with low, intermediate, and high 825T allele frequencies, respectively. In each of these three distinct cohorts, the 825T allele frequency was increased significantly in overweight (body mass index [BMI] ≥25 kg/m 2 ) and obese individuals (BMI &gt;27 kg/m 2 ) compared to those with normal weight. The 825T allele frequencies in these three BMI groups were, respectively, 29.5, 39.3, and 47.7% in Germans, 46.8, 53.9, and 58.6% in Chinese, and 83.1, 87.7, and 90.9% in South Africans. In each of these three distinct groups, the 825T allele was significantly associated with obesity with odds ratios between 2 and 3. More urban than rural black Africans were overweight despite similar 825T allele frequencies in both populations, which underscores the role of both genetic and environmental factors. BP values in young male whites increased significantly with increasing BMI values but were independent of the C825T polymorphism, suggesting that hypertension associated with the 825T allele could be a consequence of obesity. Genotyping of 5254 individuals from 55 native population samples from Africa, the Americas, Europe, Asia, Australia, and New Guinea demonstrated highest 825T allele frequencies in black Africans (82%) and intermediate values in east Asians (47%). It is anticipated that high frequencies of the 825T allele in Africans and Asians may contribute to an obesity and hypertension epidemic if Westernization of lifestyles continues.
Therapeutic Potential of Phosphodiesterase 5 Inhibition for Cardiovascular Disease
Authors: Thorsten Reffelmann, Robert A. Kloner
Journal: Circulation (2003)

S everal families of phosphodiesterases (PDE), the en- zymes catalyzing hydrolysis of cyclic (c) nucleoside monophosphates, namely, 3Ј5Ј-cAMP (cAMP) and 3Ј5Ј-cGMP (cGMP), have been identified and characterized in recent years. 1 Since selective pharmacological inhibitors of isoform 5 (a cGMP-specific PDE), such as sildenafil, tadalafil, or vardenafil, have become available, the physiological function and interaction of different PDE isoforms, 2 their tissue distribution, 2 and the therapeutic potential of PDE 5 inhibition have attracted increasing interest. 3he discovery in 1989 of sildenafil, a highly selective inhibitor of PDE 5, was the result of extensive research on chemical agents targeting PDE 5 that might potentially be useful in the treatment of coronary heart disease.Initial clinical studies on sildenafil in the early 1990s were not promising with respect to its antianginal potential.However, a remarkable side effect was reported by a number of volunteers participating in these investigations; sildenafil seemed to enhance penile erections, which soon thereafter became the main focus of further studies.PDE 5 is found in high concentration in smooth muscle cells of the corpora cavernosa. 2Relaxation of smooth muscle cells of penile arteries, arterioles, and sinusoids in response to sexual stimulation results in an increase in blood volume within the rigid tunica albuginea and compression of draining venules, and hence a penile erection.Relaxation of the arterial smooth muscles occurs after stimulation of the enzyme guanylate cyclase by nitric oxide released from nonadrenergic-noncholinergic nerves and endothelial cells, with subsequent formation of cGMP 4 (Figure 1).cGMP activates a cGMP-dependent protein kinase, which leads to phosphorylation of ion channels with the final consequence of a reduced cytosolic calcium concentration. 5Thus, sildenafil inhibiting the breakdown of cGMP was found to be effective in a high percentage of male patients suffering from erectile dysfunction. 3,6owever, as PDE 5 is expressed in various other tissues, such as the arterial vasculature, including pulmonary and coronary arteries, venous vasculature, skeletal muscles, visceral and tracheobronchial muscles, and platelets, 1,2,7,8 effects in patients are complex.In this review, we try to outline the effects of PDE 5 inhibition in addition to its efficacy in erectile dysfunction.Potential implications, and whether some of these effects are therapeutically exploitable, will be discussed.Because of limited information on newer agents, the main conclusions will be drawn from results obtained with sildenafil treatment.
Spatial heterogeneity of intracellular Ca2+ concentration in nonbeating guinea pig ventricular myocytes.
Authors: D J Williford, V K Sharma, M Korth, S S Sheu
Journal: Circulation Research (1990)

The spatial distribution of intracellular Ca2+ concentration was determined by fluorescent digital imaging microscopy in fura-2-loaded quiescent cardiac myocytes isolated from guinea pig ventricle. Fluorescent ratio images revealed discrete as well as clustered bright fluorescent spots ("hot spots"), which occupied approximately 20-50% of an individual cell's area. The fluorescent intensity and the area of the hot spots were increased by agents that deplete Ca2+ in the sarcoplasmic reticulum, namely, ryanodine (20-40 nM) and caffeine (5-15 mM). However, when cells were exposed to agents that deplete mitochondrial Ca2+, such as the protonophore, carbonyl cyanide m-chlorophenyl-hydrazone (CCCP, 100-300 nM), or the inhibitor of electron transport, antimycin A (4-40 nM), the fluorescent intensity and the area of the hot spots were reduced. These results indicate that the spatial distribution of intracellular Ca2+ concentration in the ventricular myocytes of guinea pig is quite heterogeneous. The ability of CCCP and antimycin A, but not of caffeine and ryanodine, to reduce the fluorescent intensity in the hot spots implies that Ca2+ compartmentation in the mitochondria is largely responsible for the intracellular Ca2+ heterogeneity seen in the present study.
Does nasal oxygen reduce the cardiorespiratory problems experienced by elderly patients undergoing endoscopic retrograde cholangiopancreatography?
Authors: D J Haines, D Bibbey, J R Green
Journal: Gut (1992)

Elderly patients undergoing endoscopic retrograde cholangiopancreatography (ERCP) have an increased risk of sedation related complications during the procedure. To determine whether nasal oxygen supplementation (2 l/min) reduces these risks, half of 66 patients aged over 60 undergoing ERCP using minimal midazolam sedation alone were randomised to receive nasal oxygen. The arterial oxygen saturation and pulse rate of all patients were monitored by pulse oximetry before and during the procedure. Only three patients in the oxygen supplemented group (n = 33) required any form of intervention for hypoxia compared with six in the control group (n = 33). Comparison of mean arterial oxygen saturation between the groups showed significantly higher levels in the nasal oxygen group throughout the procedure. Pulse rate comparisons showed no significant difference from control group values, both groups had short periods of significant tachycardia. We conclude that minimal sedation with midazolam alone still produces hypoxia during ERCP in a substantial number of elderly patients. Nasal oxygen supplementation increases the level of patient oxygenation and reduces the need for intervention, but does not reduce tachycardia in the elderly patient. Because hyoscine may be a significant factor contributing to the tachycardia, sparing rather than routine use of this agent is advisable.
Fibulin-1 is a novel biomarker of disease severity in pulmonary fibrosis
Authors: Janette Burgess, Jade Jaffar, Sofia Unger, Michael Keller, Tamera Corte, Paul Wolters, Luca Richeldi, Stefania Cerri, W. Scott Argraves, Judith Black, Brian Oliver
Journal: European Respiratory Journal (2013)

Idiopathic pulmonary fibrosis (IPF) is a severe form of interstitial lung disease (ILD) with a median survival post-diagnosis of 2-5 years. It is vital to distinguish IPF from other primarily inflammatory ILDs as the therapeutic options are distinct. Levels of the extracellular matrix protein fibulin-1 were evaluated in the serum and lung tissue from patients with ILD and levels correlated with lung function.  Serum and pulmonary function tests from patients with ILD were collected from 3 cohorts (Sydney, Australia, Modena, Italy and San Francisco, USA). Fibulin-1 levels in serum were analysed by western blot. Immunohistochemistry was performed on tissue sections from people with no lung disease or IPF from 3 cohorts (Sydney, Perth, Australia and Modena, Italy) and staining intensity analysed by ImageJ.  In ILD patients, serum fibulin-1 levels were associated with disease severity (composite physiologic index (CPI),DLCO% predicted) and elevated fibulin-1 levels predicted disease progression. In IPF patients, fibulin-1 serum levels were increased in patients with IPF compared to non-diseased controls (N=75 & 17; P  Serum fibulin-1 is increased in patients with IPF compared to other ILDs and a high serum fibulin-1 level is suggestive of poorer survival. Parenchymal fibulin-1 correlates strongly with poorer lung function. Fibulin-1 may be an important prognostic molecule in ILD, particularly in IPF.
Aquatic training with and without weights and its impact on agility and explosive power among volleyball players
Authors: K Kamalakkannan, N Vijayaragunathan, R Kalidasan
Journal: British Journal of Sports Medicine (2010)

The objective of the study was to investigate the impact of aquatic training with and without weights on agility and explosive power among volleyball players. Thirty male physically active and interested undergraduate Engineering volleyball players between 18 and 20 years of age volunteered as participants. Participants were randomly categorised into three groups of 10 each: Group I (control) was not exposed to any specific training/conditioning (CG), group II was involved in aquatic training (ATG) and group III was given aquatic training combined with weights (ATWG). The aquatic training package was designed by the investigators and was administered for a period of 6 weeks, 3 days a week; a session each day, each session lasted 2 h. Both experimental groups underwent their respective experimental treatment. The aquatic training schedule was specifically designed to improve the fitness levels of the volleyball players. The weight training was meted out for 60 min to group III. Aquatic training and weights were given on alternative days. Agility (shuttle run) and explosive power (broad jump) were selected as variables for this investigation. The pre and post-test were conducted 1 day before and after the experimental treatment. Analysis of covariance was used to analyse the collected data. Scheffe's test was used as a post-hoc test to determine which of the paired mean differ significantly. There was no significant difference in pre-test data of control and experimental groups: agility(s) CG 14.5±CG1.2; ATG 15.0±0.9; ATWG 14.3±0.8, post-test mean values were CG 14.5±1.2; ATG 14.9±0.9; ATWG 14.2±0.7. Pre-test explosive power (m) was CG 2.38±0.15; ATG 2.28±0.08; ATWG 2.28±0.19: Post-training mean values were: CG 2.38±0.11; ATG 2.35±0.08; ATWG 2.37±0.40. The results of the study reveal that both aquatic training and ATWG produced positive impacts on the agility and explosive power among volleyball players.
A Neuropsychological Investigation of Prefrontal Cortex Involvement in Acute Mania
Authors: Luke Clark, Susan D. Iversen, Guy M. Goodwin
Journal: American Journal of Psychiatry (2001)

OBJECTIVE: Mania has received little attention from a contemporary neuropsychological perspective despite its clear resemblance to the disinhibition syndrome sometimes seen after frontal brain injury, particularly injury to the inferior aspect of the prefrontal cortex. The purpose of this investigation was to describe the neuropsychological profile of severe acute mania by using a range of tasks selected primarily for the detection of localized neural disruption within the prefrontal cortex. METHOD: Fifteen acutely manic inpatients were compared with 30 nonpsychiatric subjects on tasks from the Cambridge Automated Neuropsychological Test Battery (Tower of London, spatial working memory, intradimensional-extradimensional attentional shift, and rapid visual information processing tasks) and on the Iowa Gambling Task, Stroop Color and Word Test, a verbal fluency task, and the California Verbal Learning Test. RESULTS: Discriminant function analysis identified deficits in sustained attention (on the rapid visual information processing task) and verbal learning (on the California Verbal Learning Test) as the best indicators of manic performance, rather than deficits on any of the tests of executive functioning. The model correctly classified 91% of subjects overall and 87% of manic subjects. Manic patients did not resemble patients with ventromedial prefrontal cortex damage in their performance on the Iowa Gambling Task. CONCLUSIONS: Acute mania is characterized by core deficits in verbal memory and sustained attention against a background of milder impairments in functions that are traditional measures of prefrontal cortex integrity (attentional set shifting, planning, working memory). The data do not implicate ventral prefrontal cortex disruption as a locus of pathology in acute mania. Verbal memory and sustained attention deficits may relate differentially to the state and trait characteristics of bipolar disorder.
Mutations of the X-linked genes encoding neuroligins NLGN3 and NLGN4 are associated with autism
Authors: Stéphane Jamain, Hélène Quach, Catalina Betancur, Maria Råstam, Catherine Colineaux, I. Carina Gillberg, Henrik Soderstrom, Bruno Giros, Marion Leboyer, Christopher Gillberg, Thomas Bourgeron
Journal: Nature Genetics (2003)
Increased Expression and Activity of CDC25C Phosphatase and an Alternatively Spliced Variant in Prostate Cancer
Authors: Mustafa Ozen, Michael Ittmann
Journal: Clinical Cancer Research (2005)

Abstract Alterations in the control of cell cycle progression have been implicated in a wide variety of malignant neoplasms, including prostate cancer. CDC25 phosphatases belong to the tyrosine phosphatase family and play a critical role in regulating cell cycle progression by dephosphorylating cyclin-dependent kinases at inhibitory residues. CDC25C plays an important role in the G2-M transition by activating Cdc2/Cyclin B1 complexes. To determine whether CDC25C activity is altered in prostate cancer, we have examined the expression of CDC25C and an alternatively spliced variant in human prostate cancer samples and cell lines. CDC25C protein is up-regulated in prostate cancer in comparison with normal prostate tissue and is present almost exclusively in its active dephosphorylated form. Expression of a biologically active alternatively spliced CDC25C isoform is also increased in prostate cancer and expression of alternatively spliced CDC25C is correlated to occurrence of biochemical (prostate-specific antigen) recurrence. We have also developed a quantitative reverse transcriptase-PCR analysis of Ki-67 expression as a method of measuring proliferative activity in prostate cancer from RNA samples. Based on this analysis of Ki67 expression, some but not all of this increase in CDC25C and its alternatively spliced variants is correlated with increased proliferation in prostate cancer. This data suggests that CDC25C might play an important role in prostate cancer progression and could be used to monitor and predict the aggressiveness of this disease.
CELLULAR MECHANISMS OF PROTEIN METABOLISM IN THE NEPHRON
Authors: Jean Oliver, Montrose J. Moses, Muriel C. MacDowell, Yin Chen Lee
Journal: The Journal of Experimental Medicine (1954)

Histochemical methods show not only the presence of absorbed protein in the cellular droplet, but also the general identity of its constituent substances with those of the mitochondrial rodlets. Both contain considerable amounts of phospholipid and probably some PNA. The reactivity of the cytoplasmic constituents in droplet and in rodlet are different, however, since in the droplet these substances stain more intensely. As judged by variations observed in this intensity during the evolution of the droplet, these constituents and the absorbed protein vary in their proportions and amount. The droplet would appear to be a highly active center of protein metabolism.
World Congress on Insulin Resistance, Diabetes, and Cardiovascular Disease: Part 4
Authors: Zachary T. Bloomgarden
Journal: Diabetes Care (2011)

This is the third of four reports on the 8th Annual World Congress on Insulin Resistance, Diabetes, and Cardiovascular Disease, held on 4–6 November 2010, in Los Angeles, California.

Ronald Krauss (Berkley, CA) discussed lipid effects of peroxisome proliferator–activated receptors (PPARs). PPARα activation reduces triglyceride-rich lipoproteins as a consequence of combined intrahepatic actions increasing fatty acid oxidation, increasing apolipoprotein (apo)A-5, and decreasing apoC-3. The LDL phenotype B, defined by small dense LDL cholesterol with low peak particle size, may be considered a specific marker for atherogenic dyslipidemia or, as Krauss termed it, “a fingerprint for this dyslipidemic phenotype” with high triglyceride, low HDL cholesterol, and high levels of apoB for a given LDL cholesterol concentration. A study of lipoprotein particle size and concentration as assessed using nuclear magnetic resonance spectroscopy among 26,836 nondiabetic women in the Women's Health Study showed that LDL cholesterol was not associated with the pattern B phenotype and that both LDL particle concentration and size were strongly and independently associated with diabetes to nearly the same degree as the A1C level (1). HDL size, HDL cholesterol, triglyceride, and VLDL size also displayed the association with the small dense LDL cholesterol phenotype, suggesting that all these measures reflect the interplay between fatty acids and lipid metabolism as they relate to insulin resistance.

PPARα activation decreases VLDL cholesterol, changes LDL cholesterol from smaller to larger size, and raises HDL cholesterol, while the lipoprotein effects of PPARδ are less well understood. Both are reported to be activated by hydrolyzed VLDL lipids, although endogenous factors activating these receptors have not been well characterized. In an in vitro study in the absence of albumin, cellular fatty acid uptake determined PPARα activation but at fatty acid levels not achievable in plasma because of the effect of albumin binding (2). One therefore needs …
Pathophysiology of bronchial smooth muscle remodelling in asthma
Authors: I. Bara, A. Ozier, J-M. Tunon de Lara, R. Marthan, P. Berger
Journal: European Respiratory Journal (2010)

Whereas the role of bronchial smooth muscle remains controversial in healthy subjects its role is well established in asthmatics. Bronchial smooth muscle contraction induces airway narrowing. The smooth muscle also contributes to bronchial inflammation by secreting a range of inflammatory mediators, recruiting and activating inflammatory cells, such as mast cells or T-lymphocytes. In addition, bronchial smooth muscle mass is significantly increased in asthma. Such an increase has been related to a deposition of extracellular matrix proteins, and an increase in both cell size and number. However, the mechanisms of this smooth muscle remodelling are complex and not completely understood. The article will review recent data regarding the pathophysiology of bronchial smooth muscle remodelling in asthma.
Both Continuous Subcutaneous Insulin Infusion and a Multiple Daily Insulin Injection Regimen With Glargine as Basal Insulin Are Equally Better Than Traditional Multiple Daily Insulin Injection Treatment
Authors: Giuseppe Lepore, Alessandro R. Dodesini, Italo Nosari, Roberto Trevisan
Journal: Diabetes Care (2003)

Diabetes Control and Complications Trial results showed that strict metabolic control may substantially reduce the risk of long-term microvascular complications (1). Over the study period, which averaged 7 years, the mean HbA1c level in the intensive group treatment was 7.2%. Current guidelines of treatment for type 1 diabetes propose a goal of HbA1c <7% (2). Nevertheless, in usual clinical practice, an acceptable metabolic control is achieved in a too low proportion of patients, even under multiple daily insulin injections (MDIs) (3). A recent meta-analysis of randomized trials concluded that continuous subcutaneous insulin infusion (CSII) permits a small improvement in blood glucose control with respect to MDIs (4). Glargine insulin is a human insulin analog that might mimic the effects of CSII at single basal infusion rate. Preliminary studies indicate that glargine may reduce the incidence of hypoglycemia and fasting blood glucose compared with NPH (5).

Whether an MDI treatment with glargine as long-acting insulin may offer similar results to those obtained with CSII is still unknown (6). For this purpose, …