tbuckley/cabot-search huggingface dataset:
N<scp>UTRITIONAL</scp> R<scp>EGULATION OF</scp> M<scp>ILK</scp> F<scp>AT</scp> S<scp>YNTHESIS</scp>
Authors: Dale E. Bauman, J. Mikko Griinari
Journal: Annual Review of Nutrition (2003)

Certain diets cause a marked reduction in milk fat production in ruminants. Commonly referred to as milk fat depression (MFD), the mechanism involves an interrelationship between rumen microbial processes and tissue metabolism. Numerous theories to explain this interrelationship have been proposed and investigations offer little support for theories that are based on a limitation in the supply of lipogenic precursors. Rather, the basis involves alterations in rumen biohydrogenation of dietary polyunsaturated fatty acids and a specific inhibition of mammary synthesis of milk fat. The biohydrogenation theory proposes that under certain dietary conditions, typical pathways of rumen biohydrogenation are altered to produce unique fatty acid intermediates that inhibit milk fat synthesis. Trans-10, cis-12 conjugated linoleic acid (CLA) has been identified as one example that is correlated with the reduction in milk fat. Investigations with pure isomers have shown that trans-10, cis-12 CLA is a potent inhibitor of milk fat synthesis, and similar to diet-induced MFD, the mechanism involves a coordinated reduction in mRNA abundance for key enzymes involved in the biochemical pathways of fat synthesis. A more complete identification of these naturally produced inhibitors of fat synthesis and delineation of cellular mechanisms may offer broader opportunities for application and understanding of the regulation of lipid metabolism.
Relation Between Blood Glucose and Coronary Mortality Over 33 Years in the Whitehall Study
Authors: Eric J. Brunner, Martin J. Shipley, Daniel R. Witte, John H. Fuller, Michael G. Marmot
Journal: Diabetes Care (2006)

OBJECTIVE—Glucose intolerance is a risk factor for coronary disease, but there is uncertainty about the shape of the dose-response relationship between glucose level and risk of coronary mortality. We examined the prospective relation of 2-h postload blood glucose (2hBG) with coronary and other major causes of mortality over 33 years. RESEARCH DESIGN AND METHODS—A 50-g oral glucose tolerance test (OGTT) was performed at baseline (1967–1969) in 17,869 male civil servants aged 40–64 years. RESULTS—There were 3,561 coronary deaths during 451,787 person-years of observation. All-cause, cardiovascular, and respiratory mortality were elevated among participants with glucose intolerance. The hazard of coronary mortality rose from 2hBG = 4.6 mmol/l (83 mg/dl [95% CI 4.2–5.3]). The dose-response relation was best fitted by a single slope above this level, with no evidence of nonlinearity, compared with Cox models using other threshold levels, and those containing log 2hBG terms. There was no evidence for a dose-response relationship below 2hBG = 4.6 mmol/l. Between this level and 11.1 mmol/l (200 mg/dl), the age-adjusted hazard ratio was 3.62 (95% CI 2.3–5.6). The graded relationship was attenuated by 45% after adjustment for baseline coronary heart disease (CHD), BMI, systolic blood pressure, blood cholesterol, smoking, physical activity, lung function, and employment grade. CONCLUSIONS—A threshold model with linear slope best described the dose-response relationship between postload blood glucose and CHD mortality risk.
Long-Term Results (Three to Five Years) of the Restenosis Intrastent: Balloon Angioplasty Versus Elective Stenting (RIBS) Randomized Study
Authors: Fernando Alfonso, José M. Augé, Javier Zueco, Armando Bethencourt, José R. López-Mínguez, José M. Hernández, Juan A. Bullones, Isabel Calvo, Enrique Esplugas, María J. Pérez-Vizcayno, Raul Moreno, Cristina Fernández, Rosana Hernández, Vasco Gama-Ribeiro
Journal: Journal of the American College of Cardiology (2005)
Does This Patient Have Obstructive Sleep Apnea?
Authors: Kathryn A. Myers, Marko Mrkobrada, David L. Simel
Journal: JAMA (2013)

Obstructive sleep apnea is a common disease, responsible for daytime sleepiness. Prior to referring patients for definitive testing, the likelihood of obstructive sleep apnea should be established in the clinical examination.To systematically review the clinical examination accuracy in diagnosing obstructive sleep apnea.MEDLINE and reference lists from articles were searched from 1966 to June 2013. Titles and abstracts (n = 4449) were reviewed for eligibility and appraised for evidence levels.For inclusion, studies must have used full, attended nocturnal polysomnography for the reference standard (n = 42).Community and referral-based prevalence of obstructive sleep apnea; accuracy of symptoms and signs for the diagnosis of obstructive sleep apnea.The prevalence of sleep apnea in community-screened patients is 2% to 14% (sample sizes 360-1741) and 21% to 90% (sample sizes 42-2677) for patients referred for sleep evaluation. The prevalence varies based on the apnea-hypopnea index (AHI) threshold used for the evaluation (≥5 events/h, prevalence 14%; ≥15/h, prevalence 6%) and whether the disease definition requires symptoms in addition to an abnormal AHI (≥5/h with symptoms, prevalence 2%-4%). Among patients referred for sleep evaluation, those with sleep apnea weighed more (summary body mass index, 31.4; 95% CI, 30.5-32.2) than those without sleep apnea (summary BMI, 28.3; 95% CI, 27.6-29.0; P < .001 for the comparison). The most useful observation for identifying patients with obstructive sleep apnea was nocturnal choking or gasping (summary likelihood ratio [LR], 3.3; 95% CI, 2.1-4.6) when the diagnosis was established by AHI ≥10/h). Snoring is common in sleep apnea patients but is not useful for establishing the diagnosis (summary LR, 1.1; 95% CI, 1.0-1.1). Patients with mild snoring and body mass index lower than 26 are unlikely to have moderate or severe obstructive sleep apnea (LR, 0.07; 95% CI, 0.03-0.19 at threshold of AHI ≥15/h).Nocturnal gasping or choking is the most reliable indicator of obstructive sleep apnea, whereas snoring is not very specific. The clinical examination of patients with suspected obstructive sleep apnea is useful for selecting patients for more definitive testing.
Genetic Aspects of Gout
Authors: M A Becker, J E Seegmiller
Journal: Annual Review of Medicine (1974)

At the present time medicine faces a curious dichotomy in the depth of its under­ standing of hereditary diseases that seems out of harmony with the ground swell of desire for more effective delivery of health care. An increasing number of the rare and exotic recessively inherited· diseases are rapidly being characterized as deficien­ cies of specific enzymes and provide valuable models of gene action. Yet, the specific hereditary factors underlying the more common, usually dominantly inherited dis­ orders such as diabetes, hypertension, cardiovascular disease, mental illness, and some forms of arthritis continue to elude intensive investigations. In this presenta­ tion we will delineate the beginning that has been made in the identification of specific genetically determined enzyme abnormalities and biochemical mechanisms responsible for the development of gouty arthritis. Since one of these well-defined genetic defects apparently is dominantly inherited, it may well set a pattern for an approach to other more common dominantly inherited diseases. As a disorder well known in antiquity, gout was recognized quite early as a familial disease (1). Only when the biochemical basis of the malady was identified, however, was an ordered approach to the genetics of gout possible. Thus, the identification of uric acid renal stones by Scheele (1776) and the classical demonstra­ tion of hyperuricemia in gouty individuals by A. B. Garrod in 1 848 (2) provided the impetus to the study of purine metabolism, which eventuated in the concept of gout as a clinical expression of the excessive accumulation of a normal but relatively insoluble metabolic product, uric acid. In 1931, A. E. Garrod included gout among the inborn errors of metabolism (3), a class of hereditary metabolic abnormalities which he had first proposed in the Croonian Lectures of 1908 (4). From his clinical observations, Garrod concluded that gout was a dominantly inherited trait, incompletely expressed especially in women (3). Moreover, he suggested that an even greater number of hyperuricemic but asymptomatic persons would be found among the relatives of gouty individuals.
This Is the Decade That Is
Authors: M. Therese Southgate
Journal: JAMA (1980)

Two years ago we tried an experiment in which each member ofThe Journal's Editorial Board chose what he considered to be the two or three most noteworthy aspects of his particular specialty at that time. He then condensed the ideas into an essay of 1,000 words or so, and the entire collection of 18 essays was published as a special issue ofThe Journalcalled CONTEMPO (Feb 6, 1978). The reception of that issue encouraged us to repeat the experiment the following year (CONTEMPO '79, March 30, 1979), and the reader response assured us that we were, indeed, filling a need. Thus, we are pleased to bring you CONTEMPO '80. Although three times might not establish tradition, we are encouraged that these "annual rites of spring" may well become such. It should be noted also in this respect that the date has been moved to the first week
Cystic fibrosis ciliary dyskinesia substances and pulmonary disease. Effects of ciliary dyskinesia substances on neutrophil movement in vitro.
Authors: G B Wilson, H H Fudenberg, M T Parise, E Floyd
Journal: Journal of Clinical Investigation (1981)

Cultured mononuclear cells (MNC) from individuals homozygous or heterozygous for the defective gene causing the inherited disease cystic fibrosis (CF) synthesize three unusual "mediators" termed ciliary dyskinesia substances (CDS), which markedly affect tracheal mucociliary systems in vitro. MNC cultures from normal healthy controls do not accumulate any CDS, whereas MNC cultures from non-CF patients controls with pulmonary disease synthesized at least one CDS. The possible involvement of the CDS in pulmonary disease is being investigated. In this study, we sought to determine whether the CDS could be chemoattractants for polymorphonuclear neutrophils (PMN), since they have characteristics in common with known chemoattractants generated by alveolar macrophages. Our analyses of crude MNC culture supernates indicated that cultures from both CF genotypes accumulate significantly higher levels of PMN chemoattractants than do analogous cultures from normal healthy controls. CF homozygote MNC also generated more activity than MNC from patient controls with chronic pulmonary disease. Fractionation of MNC culture supernates by gel permeation chromatography and characterization of active fractions demonstrated six distinct PMN chemoattractants in cultures from CF genotypes; five were also present in patient control and four in normal healthy control cultures. The excessive chemoattractant activity in MNC cultures from CF genotypes and patient controls was due to several different substances produced by monocytes: (a) two components of 1,000-3,500 mol wt. (b) two fragments of C5, and (c) a fragment of C3. One C5 fragment had ciliary dyskinesia activity, the other did not. The C3 fragment chemoattractant also had ciliary dyskinesia activity and was not found in MNC cultures from patient controls. A third CDS, Which is CF-specific (5,000 mol wt), was neither chemotactic not chemokinetic and did not inhibit random PMN migration; however, fractions containing this CF-specific CDS completely inhibited PMN chemotaxis in response to three different chemoattractants. We conclude that all of the CDS can potentially play a role in the pathophysiology of lung disease, as judged by their effects on PMN movement in vitro.
Combinatorial Expression of TRPV Channel Proteins Defines Their Sensory Functions and Subcellular Localization in C. elegans Neurons
Authors: David M. Tobin, David M. Madsen, Amanda Kahn-Kirby, Erin L. Peckol, Gary Moulder, Robert Barstead, Andres V. Maricq, Cornelia I. Bargmann
Journal: Neuron (2002)
Methylisothiazolinone contact allergy: a review
Authors: M.D. Lundov, T. Krongaard, T.L. Menné, J.D. Johansen
Journal: British Journal of Dermatology (2011)

In the early 2000s the preservative methylisothiazolinone (MI) was released as an individual preservative for industrial products and, in 2005, it was permitted for use in cosmetic products. Up until then MI had been used only in combination with methylchloroisothiazolinone (MCI). MCI/MI is one of the most frequent causes of preservative contact allergy and early studies showed that both MI and MCI are sensitizers. The prevalence of MI contact allergy is already around 1·5% and sources of exposure are associated with occupation, cosmetic products or household products. Use of MI in industrial products is not restricted and cases of occupational contact allergy to MI, e.g. in painters, are reported. The frequency of use of MI in cosmetics is low, around 1%, while up to 16·5% of household products were preserved with MI. We found 19 (1·5%) out of 1272 cosmetic products labelled with MI, primarily rinse‐off products, and analysed the concentration of MI by high‐performance‐liquid‐chromatography the ultraviolet and mass spectrometry detection. The use concentration ranged between 2 and 100 ppm. Repeated exposure to MI showed that many patients allergic to MI reacted to 50 ppm which is half the maximum permitted concentration of MI in cosmetics. The recent cases and prevalence studies on MI contact allergy could be the first sign of an epidemic of MI contact allergy. The development in prevalence of MI contact allergy should be closely monitored by including MI in the European Baseline Series at 2000 ppm.
Hamlet's Horatio and the Therapeutic Mode
Authors: HOWARD M. FEINSTEIN
Journal: American Journal of Psychiatry (1967)

The legitimate area of action for the psychiatrist is not yet clearly defined. This paper studies psychotherapy, comparing it with the role expectations of friendship. Parallels are drawn from Shakespeare's Hamlet between the true friendship of Horatio for Hamlet and the psychiatrist's stance toward the other, and between the false friendship of Rosencrantz and Guildenstern for Hamlet and the psychiatrist's action on behalf of society. The author urges the psychiatrist to carefully consider the ethical implications of "pseudotherapy."
Didgeridoo playing as alternative treatment for obstructive sleep apnoea syndrome: randomised controlled trial
Authors: Milo A Puhan, Alex Suarez, Christian Lo Cascio, Alfred Zahn, Markus Heitz, Otto Braendli
Journal: BMJ (2005)

<h3>Abstract</h3> <b>Objective</b> To assess the effects of didgeridoo playing on daytime sleepiness and other outcomes related to sleep by reducing collapsibility of the upper airways in patients with moderate obstructive sleep apnoea syndrome and snoring. <b>Design</b> Randomised controlled trial. <b>Setting</b> Private practice of a didgeridoo instructor and a single centre for sleep medicine. <b>Participants</b> 25 patients aged &gt; 18 years with an apnoea-hypopnoea index between 15 and 30 and who complained about snoring. <b>Interventions</b> Didgeridoo lessons and daily practice at home with standardised instruments for four months. Participants in the control group remained on the waiting list for lessons. <b>Main outcome measure</b> Daytime sleepiness (Epworth scale from 0 (no daytime sleepiness) to 24), sleep quality (Pittsburgh quality of sleep index from 0 (excellent sleep quality) to 21), partner rating of sleep disturbance (visual analogue scale from 0 (not disturbed) to 10), apnoea-hypopnoea index, and health related quality of life (SF-36). <b>Results</b> Participants in the didgeridoo group practised an average of 5.9 days a week (SD 0.86) for 25.3 minutes (SD 3.4). Compared with the control group in the didgeridoo group daytime sleepiness (difference −3.0, 95% confidence interval −5.7 to −0.3, P = 0.03) and apnoea-hypopnoea index (difference −6.2, −12.3 to −0.1, P = 0.05) improved significantly and partners reported less sleep disturbance (difference −2.8, −4.7 to −0.9, P &lt; 0.01). There was no effect on the quality of sleep (difference −0.7, −2.1 to 0.6, P = 0.27). The combined analysis of sleep related outcomes showed a moderate to large effect of didgeridoo playing (difference between summary z scores −0.78 SD units, −1.27 to −0.28, P &lt; 0.01). Changes in health related quality of life did not differ between groups. <b>Conclusion</b> Regular didgeridoo playing is an effective treatment alternative well accepted by patients with moderate obstructive sleep apnoea syndrome. <b>Trial registration</b> ISRCTN: 31571714.
Nilotinib Attenuates Renal Injury and Prolongs Survival in Chronic Kidney Disease
Authors: Masayuki Iyoda, Takanori Shibata, Yuki Hirai, Yoshihiro Kuno, Tadao Akizawa
Journal: Journal of the American Society of Nephrology (2011)

The tyrosine kinase inhibitor imatinib is beneficial in experimental renal diseases, but the effect of the new tyrosine kinase inhibitor nilotinib on the progression of renal failure is unknown. We administered either nilotinib or vehicle to Sprague-Dawley rats beginning 2 weeks after 5/6 nephrectomy (Nx) or laparotomy and continuing for 8 weeks. Serum creatinine levels were significantly lower in the nilotinib group after 6 and 8 weeks of treatment. Furthermore, nilotinib-treated rats had less proteinuria, attenuated glomerulosclerosis and tubulointerstitial damage, and reduced macrophage infiltration into the tubulointerstitium. Treatment with nilotinib also significantly decreased renal cortical expression of profibrogenic genes, such as IL-1β and monocyte chemotactic protein-1, which correlated closely with the tubulointerstitial damage score and ED1-positive macrophages score. In addition, nilotinib treatment significantly prolonged survival. Taken together, these results suggest that nilotinib may limit the progression of chronic kidney disease.
Systemic cytokine response in patients with community-acquired pneumonia
Authors: H Endeman, S C A Meijvis, G T Rijkers, H van Velzen-Blad, C H M van Moorsel, J C Grutters, D H Biesma
Journal: European Respiratory Journal (2010)

The role of individual cytokines and polymorphisms in pneumonia has been described, but the relationship between different cytokines and polymorphisms in relation to causative microorganisms, antibiotics, corticosteroids and clinical course has not. This study questions the relationship between cytokines, polymorphisms and clinical characteristics of pneumonia. Patients diagnosed with pneumonia were included in the study. Serum cytokine levels were measured during hospital stay, genotyping was performed, causative microorganisms were identified and patients were monitored throughout the hospital stay. In 201 patients with pneumonia interleukin (IL)-1 receptor antagonist (IL-1RA), IL-6, IL-8 and IL-10 acted as acute phase proteins. After admission, the levels of these cytokines decreased rapidly. Single nucleotide polymorphisms did not influence cytokine production and were not associated with clinical outcome. Cytokine serum levels were significantly higher in patients with pneumococcal pneumonia. The decrease in levels of cytokines was independently influenced by the start of corticosteroid therapy. IL-1RA, IL-6, IL-8 and IL-10 are acute phase proteins, independent of genotype. Their levels are influenced by the nature of the causative microorganism and the start of corticosteroids therapy.
Relation of Lifetime Trauma and Depressive Symptoms to Mortality in HIV
Authors: Jane Leserman, Brian Wells Pence, Kathryn Whetten, Michael J Mugavero, Nathan M Thielman, Marvin S Swartz, Dalene Stangl
Journal: American Journal of Psychiatry (2007)

In an era of highly active antiretroviral therapies, the authors needed to confirm previous findings showing that stress and depression have an impact on HIV disease progression. The goal of the current study was to examine the effects of lifetime trauma, recent stressful events, and depression on all-cause and AIDS-related mortality among HIV-infected men and women. The authors hypothesized that these psychosocial variables would predict significantly faster HIV-specific and all-cause mortality.The authors consecutively sampled HIV-infected men and women who received care at one of eight infectious diseases clinics in five Southeastern states. The sample included 490 patients who were followed by interview for 27 months and followed with their medical records for up to 41 months.There were 29 deaths; 16 were AIDS-related. More lifetime trauma and antigenic marker on helper/inducer T cells (CD4)<200 significantly predicted faster all-cause and AIDS-related mortality. For those at or above the median in trauma, the all-cause death rate was 3.54 per 100 person-years, compared to 1.72 for those below the median. For those at or above the median in trauma, the AIDS-related death rate was 2.13 per 100 person-years, compared to 0.77 for those below the median. Depressive symptoms and higher baseline viral load were significantly related to greater risk of AIDS-related mortality.Further research is needed to determine if interventions to address trauma and depression can modify these detrimental effects on HIV.
Non-conjugated chenodeoxycholate induces severe mitochondrial damage and inhibits bicarbonate transport in pancreatic duct cells
Authors: J. Maleth, V. Venglovecz, Z. Razga, L. Tiszlavicz, Z. Rakonczay, P. Hegyi
Journal: Gut (2010)

We read the manuscripts by Lee and Muallem1 and Venglovecz et al 2 recently published in Gut with great interest. In both articles the authors highlighted the role of pancreatic ducts in maintaining the integrity of the pancreas. Venglovecz et al showed that a high concentration of the non-conjugated chenodeoxycholate (CDC) inhibits pancreatic ductal bicarbonate secretion; however, the mechanisms of the inhibition were not clarified. This is a follow-up study in which we show that this reduction of ductal bicarbonate secretion by CDC is evoked by inhibition of glycolytic and oxidative (caused by severe mitochondrial damage) metabolism with a consequent depletion of intracellular ATP levels.

Physiologically, pancreatic ductal fluid and HCO3− secretion are necessary to wash out the digestive enzymes from the acinar cells into the duodenum. Under pathophysiological conditions toxic factors (such as bile acids and ethanol) involved in the pathogenesis of acute pancreatitis have dual effects on ductal HCO3− secretion.1 Low doses of CDC and ethanol were found to stimulate fluid and HCO3− secretion. However, these toxic agents in high concentrations inhibit the secretion. These data suggest that an elevation in pancreatic ductal fluid and HCO3− secretion may have protective roles. However, since under physiological conditions the pressure in the main pancreatic duct is higher than in the bile ducts, it is still controversial as to whether bile acids enter the pancreatic ductal tree.

We have recently shown that a high concentration (1 mM) of the non-conjugated bile acid CDC has strong inhibitory effects on the activities of acid/base transporters (Na+/H+ exchanger (NHE), Na+/HCO3− cotransporter (NBC) …
Dendritic cells pulsed with recombinant HBV envelope proteins elicit a TH2 type immune response and decrease NKT lymphocytes thus preventing the induction of viral specific immunity
Authors: O. Shibolet, A. Roslana, I. Zolotarov, B. Thalenfeld, D. Engelhardt, E. Rabbani, Y. Ilan
Journal: Journal of Hepatology (2003)