tbuckley/cabot-search huggingface dataset:
EFFECTS OF BACTERIAL ENDOTOXIN ON METABOLISM
Authors: L. Joe Berry, Dorothy S. Smythe, Leona G. Young
Journal: The Journal of Experimental Medicine (1959)

Mice of different strains were protected against the lethal effect of bacterial endotoxin by concurrent injections of cortisone. Either inadequate amounts of cortisone or excessive quantities of endotoxin voided the protection. Analyses of blood sugar, liver glycogen, muscle glycogen, and total body carbohydrate in the skinned eviscerated carcass were carried out on different strains of mice given endotoxin and/or cortisone. Poisoned animals were virtually depleted of all carbohydrate while mice given cortisone alone had concentrations of carbohydrate from three to four times that of normal mice. Mice given a lethal amount of endotoxin and a protective dose of cortisone had two to three times as much carbohydrate as animals injected with the same amount of endotoxin alone but significantly less than that found in normal mice. Dibenzyline failed to alter the lethal effect of endotoxin and to reduce the carbohydrate loss that accompanied endotoxin administration. Endotoxin, at the dosage level employed, lowered the temperature of mice 2 degrees -3 degrees C. during the first hour or two postinjection and the temperature remained essentially unaltered during the next 4 to 5 hours. Loss in body carbohydrate in endotoxin-poisoned mice cannot be explained, therefore, as the result of an elevated metabolic rate accompanying hyperthermia. Endotoxin prevented the conversion of injected glucose into liver glycogen but not into muscle glycogen. Mouse liver mitochondria, in the presence of endotoxin, released from ATP approximately the same amount of inorganic phosphate as that released in the presence of dinitrophenol.
Give your heart a chance: match the muscle to the vessel
Authors: S. T. Andreadis
Journal: Cardiovascular Research (2013)

This editorial refers to ‘Serum-free differentiation of functional human coronary-like vascular smooth muscle cells from embryonic stem cells’ by El-Mounayri et al ., pp. 125–135, this issue. 

Trace lineage studies have provided strong evidence that vascular smooth muscle is a mosaic tissue deriving from multiple independent developmental origins including the neuro-ectoderm-derived neural crest, lateral plate mesoderm, and paraxial mesoderm.1 However, the differences between vascular smooth muscle cells (VSMCs) of different origins remain largely unexplored, especially for human cells. In addition, the relationship between pericytes surrounding the vessel wall and VSMC is not well understood. It is also widely recognized that blood vessels in certain anatomic locations are more likely to develop vascular disease despite the systemic nature of risk factors such as hypercholesterolaemia or diabetes.2 The different origin of VSMCs is thought to be a possible contributor to this site-specific pre-disposition to vascular disease, suggesting that development of site-specific treatment(s) might provide more effective therapeutic options. Finally, donor ageing and culture senescence were shown to impair both the proliferation and contractile function of VSMCs,3 necessitating the development of novel approaches to restore their regenerative potential.4

These reasons led several investigators to explore ways to derive …
Prospective Study of Predictors of Vitamin D Status and Cancer Incidence and Mortality in Men
Authors: Edward Giovannucci, Yan Liu, Eric B. Rimm, Bruce W. Hollis, Charles S. Fuchs, Meir J. Stampfer, Walter C. Willett
Journal: JNCI Journal of the National Cancer Institute (2006)

Vitamin D has potent anticancer properties, especially against digestive-system cancers. Many human studies have used geographic residence as a marker of solar ultraviolet B and hence vitamin D exposure. Here, we considered multiple determinants of vitamin D exposure (dietary and supplementary vitamin D, skin pigmentation, adiposity, geographic residence, and leisure-time physical activity-to estimate sunlight exposure) in relation to cancer risk in the Health Professionals Follow-Up Study.Among 1095 men of this cohort, we quantified the relation of these six determinants to plasma 25-hydroxy-vitamin D [25(OH)D] level by use of a multiple linear regression model. We used results from the model to compute a predicted 25(OH)D level for each of 47,800 men in the cohort based on these characteristics. We then prospectively examined this variable in relation to cancer risk with multivariable Cox proportional hazards models.From 1986 through January 31, 2000, we documented 4286 incident cancers (excluding organ-confined prostate cancer and nonmelanoma skin cancer) and 2025 deaths from cancer. From multivariable models, an increment of 25 nmol/L in predicted 25(OH)D level was associated with a 17% reduction in total cancer incidence (multivariable relative risk [RR] = 0.83, 95% confidence interval [CI] = 0.74 to 0.92), a 29% reduction in total cancer mortality (RR = 0.71, 95% CI = 0.60 to 0.83), and a 45% reduction in digestive-system cancer mortality (RR = 0.55, 95% CI = 0.41 to 0.74). The absolute annual rate of total cancer was 758 per 100,000 men in the bottom decile of predicted 25(OH)D and 674 per 100,000 men for the top decile; these respective rates were 326 per 100,000 and 277 per 100,000 for total cancer mortality and 128 per 100,000 and 78 per 100,000 for digestive-system cancer mortality. Results were similar when we controlled further for body mass index or physical activity level.Low levels of vitamin D may be associated with increased cancer incidence and mortality in men, particularly for digestive-system cancers. The vitamin D supplementation necessary to achieve a 25(OH)D increment of 25 nmol/L may be at least 1500 IU/day.
A Role for Uric Acid in the Progression of Renal Disease
Authors: Duk-Hee Kang, Takahiko Nakagawa, Lili Feng, Susumu Watanabe, Lin Han, Marilda Mazzali, Luan Truong, Raymond Harris, Richard J Johnson
Journal: Journal of the American Society of Nephrology (2002)

ABSTRACT. Hyperuricemia is associated with renal disease, but it is usually considered a marker of renal dysfunction rather than a risk factor for progression. Recent studies have reported that mild hyperuricemia in normal rats induced by the uricase inhibitor, oxonic acid (OA), results in hypertension, intrarenal vascular disease, and renal injury. This led to the hypothesis that uric acid may contribute to progressive renal disease. To examine the effect of hyperuricemia on renal disease progression, rats were fed 2% OA for 6 wk after 5/6 remnant kidney (RK) surgery with or without the xanthine oxidase inhibitor, allopurinol, or the uricosuric agent, benziodarone. Renal function and histologic studies were performed at 6 wk. Given observations that uric acid induces vascular disease, the effect of uric acid on vascular smooth muscle cells in culture was also examined. RK rats developed transient hyperuricemia (2.7 mg/dl at week 2), but then levels returned to baseline by week 6 (1.4 mg/dl). In contrast, RK+OA rats developed higher and more persistent hyperuricemia (6 wk, 3.2 mg/dl). Hyperuricemic rats demonstrated higher BP, greater proteinuria, and higher serum creatinine than RK rats. Hyperuricemic RK rats had more renal hypertrophy and greater glomerulosclerosis (24.2 ± 2.5 versus 17.5 ± 3.4%; P < 0.05) and interstitial fibrosis (1.89 ± 0.45 versus 1.52 ± 0.47; P < 0.05). Hyperuricemic rats developed vascular disease consisting of thickening of the preglomerular arteries with smooth muscle cell proliferation; these changes were significantly more severe than a historical RK group with similar BP. Allopurinol significantly reduced uric acid levels and blocked the renal functional and histologic changes. Benziodarone reduced uric acid levels less effectively and only partially improved BP and renal function, with minimal effect on the vascular changes. To better understand the mechanism for the vascular disease, the expression of COX-2 and renin were examined. Hyperuricemic rats showed increased renal renin and COX-2 expression, the latter especially in preglomerular arterial vessels. In in vitro studies, cultured vascular smooth muscle cells incubated with uric acid also generated COX-2 with time-dependent proliferation, which was prevented by either a COX-2 or TXA-2 receptor inhihbitor. Hyperuricemia accelerates renal progression in the RK model via a mechanism linked to high systemic BP and COX-2-mediated, thromboxane-induced vascular disease. These studies provide direct evidence that uric acid may be a true mediator of renal disease and progression.
Serotonergic Stimulation of the Genioglossus and the Response to Nasal Continuous Positive Airway Pressure
Authors: JAGADEESHAN SUNDERRAM, RICHARD A. PARISI, RICHARD J. STROBEL
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

In obstructive sleep apnea (OSA), abnormal pharyngeal collapsibility may be offset by increased mechanoreflex-mediated activity of dilator muscles while awake, but this reflex is inhibited during sleep and during application of nasal continuous positive airway pressure (CPAP). Direct activation of upper airway (UA) motor neurons in the hypoglossal nucleus by a selective serotonin reuptake inhibitor (SSRI), paroxetine hydrochloride, may increase genioglossal electromyographic (EMG) activity (EMGgg) in a manner resistant to mechanoreflex inhibition. We studied the effects of paroxetine on EMGgg using an intraoral surface electrode during eupnea or room air breathing (RA), hypercapnia (HYP), and CPAP application in the presence of hypercapnia (CPAP + HYP) in 11 normal volunteers, using a double-blind, placebo-controlled crossover design. After 5 d of paroxetine, EMGgg activity increased significantly within each condition (p = 0.02). EMGgg during the conditions of HYP and HYP + CPAP were significantly greater than during RA for both placebo and paroxetine treatments (p = 0.006). EMGgg activity in HYP persisted during HYP + CPAP on paroxetine (183% versus 182% of placebo, respectively). We conclude that paroxetine produces an augmentation in EMGgg in normal subjects during wakefulness and that this effect persists during mechanoreflex inhibition. This is consistent with a central serotonergic effect.
Can a Valid Diagnosis of Disruptive Behavior Disorder Be Made in Preschool Children?
Authors: Kate Keenan, Lauren S. Wakschlag
Journal: American Journal of Psychiatry (2002)

OBJECTIVE: Disruptive behavior problems are the most common reason preschool children come to mental health clinics. Yet consensus on the conceptualization and measurement of such problems in young children is lacking. DSM-IV is the most widely used nosologic system for children, but the majority of the validation sample consisted of school-age children and adolescents. It is debatable whether behavioral problems in young children should be considered within a diagnostic framework at all, since normative behavioral disruption occurs during the preschool period. Developing valid methods for assessing child behavior problems across development is critical for etiologic and prevention research. METHOD: The authors compare different approaches to conceptualizing disruptive behavior in young children, review evidence for the construct validity of DSM-based oppositional defiant disorder and conduct disorder in preschool children, and outline an agenda for future research. RESULTS AND CONCLUSIONS: Typical and atypical behavior problems can be differentiated in preschool children, and the DSM framework, with some modification to address the child's developmental level, appears to be a valid method for identifying preschool children with disruptive behavior that is impairing. Empirical investigation is needed to standardize modification of existing assessment tools so that they can be used with preschool children and to develop more clinically sensitive methods for using observational data in assessment and for establishing the child's level of development.
Identification of a Predictive Biomarker for Hematologic Toxicities of Gemcitabine
Authors: Junichi Matsubara, Masaya Ono, Ayako Negishi, Hideki Ueno, Takuji Okusaka, Junji Furuse, Koh Furuta, Emiko Sugiyama, Yoshiro Saito, Nahoko Kaniwa, Junichi Sawada, Kazufumi Honda, Tomohiro Sakuma, Tsutomu Chiba, Nagahiro Saijo, Setsuo Hirohashi, Tesshi Yamada
Journal: Journal of Clinical Oncology (2009)

Purpose Gemcitabine monotherapy is the current standard for patients with advanced pancreatic cancer, but the occurrence of severe neutropenia and thrombocytopenia can sometimes be life threatening. This study aimed to discover a new diagnostic method for predicting the hematologic toxicities of gemcitabine. Patients and Methods Using quantitative mass spectrometry (MS), we compared the baseline plasma proteomes of 25 patients who had developed severe hematologic adverse events (grade 3 to 4 neutropenia and/or grade 2 to 4 thrombocytopenia) within the first two cycles of gemcitabine with those of 22 patients who had not (grade 0). Results We identified 757 peptide peaks whose intensities were significantly different (P &lt; .001, Welch t test) among a total of 60,888. The MS peak with the highest statistical significance (P = .0000282) was revealed to be derived from haptoglobin by tandem MS. A scoring system (nomogram) based on the values of haptoglobin, haptoglobin phenotype, neutrophil count, platelet count, and body-surface area was constructed to estimate the risk of hematologic adverse events (grade 3 to 4 neutropenia and/or grade 2 to 4 thrombocytopenia) with an area under curve value of 0.782 in a cohort of 166 patients with pancreatic cancer. Predictive ability of the system was confirmed in two independent validation cohorts consisting of 87 and 52 patients with area under the curve values of 0.655 and 0.747, respectively. Conclusion Although the precise mechanism responsible for the correlation of haptoglobin with the future onset of hematologic toxicities remains to be clarified, our prediction model seems to have high practical utility for tailoring the treatment of patients receiving gemcitabine.
Art and the thyroid gland
Authors: Peter Perkins
Journal: Journal of the Royal Society of Medicine (2011)

Art and medicine often overlap to the mutual advantage of both disciplines. The fascinating series on the discovery of thyroid replacement therapy and inter alia the unfolding scientific tale of the function of the thyroid gland, previously a mysterious neck swelling1,2 reminds one of the pre-Raphaelite Brotherhood school of painting. Also in the late 19th century, with their female subjects: wistful, dreamy facial expressions, long necks and prominent thyroid glands, strikingly exemplified by Dante Gabriel Rossetti, e.g. Bocca Baciata (1859) and La Bionda del Balcone (1868).

As a London medical student in the 1970s I remember being told that women are allegedly most beautiful around puberty and pregnancy, a time when physiological enlargement of the thyroid gland is the norm. A visit to The Tate Britain gallery and an appreciation of the so-called artistic license proved doubly educational. Finally the Sistine Chapel presents one with Michelangelo's ‘divine goitre’, the Creator separating light from darkness.3
Which Targets in Clinical Practice Guidelines Are Associated with Improved Survival in a Large Dialysis Organization?
Authors: Francesca Tentori, William C. Hunt, Mark Rohrscheib, Min Zhu, Christine A. Stidley, Karen Servilla, Dana Miskulin, Klemens B. Meyer, Edward J. Bedrick, H. Keith Johnson, Philip G. Zager
Journal: Journal of the American Society of Nephrology (2007)

Professional organizations have developed practice guidelines in the hope of improving clinical outcomes. The National Kidney Foundation's Kidney Disease Outcomes Quality Initiative (KDOQI) has set targets for dialysis dosage (single-pool Kt/V), hematocrit, serum albumin, calcium, phosphorus, parathyroid hormone, and BP for hemodialysis (HD) patients. Several guidelines are largely based on results from observational studies. In contrast to other parameters, BP values within the KDOQI guidelines have been associated with increased mortality. Therefore, it was postulated that having multiple parameters that satisfy the current guidelines, except those for BP, is associated with improved survival among HD patients. A retrospective analysis was conducted of incident HD patients who were treated at facilities operated by Dialysis Clinic Inc., a not-for-profit dialysis provider, between January 1, 1998, and December 31, 2004 (n = 13,792). Cox proportional hazards models were used to assess the association between satisfying guidelines and mortality. Values within guidelines for single-pool Kt/V, hematocrit, serum albumin, calcium, phosphorus, and parathyroid hormone were associated with decreased mortality (P < or = 0.0001). The largest survival benefit was found for serum albumin (hazard ratio [HR] 0.27; 95% confidence interval [CI] 0.24 to 0.31). Satisfying these six guidelines simultaneously was associated with an 89% reduction in mortality (HR 0.11; 95% CI 0.06 to 0.19]). Conversely, BP values satisfying the guideline were associated with increased mortality (HR 1.90; 95% CI 1.73 to 2.10). Because this target was largely extrapolated from the general population, a randomized, controlled trial is needed to identify the optimal BP for HD patients.
Liberal or Restrictive Transfusion in High-Risk Patients after Hip Surgery
Authors: Jeffrey L. Carson, Michael L. Terrin, Helaine Noveck, David W. Sanders, Bernard R. Chaitman, George G. Rhoads, George Nemo, Karen Dragert, Lauren Beaupre, Kevin Hildebrand, William Macaulay, Courtland Lewis, Donald Richard Cook, Gwendolyn Dobbin, Khwaja J. Zakriya, Fred S. Apple, Rebecca A. Horney, Jay Magaziner
Journal: New England Journal of Medicine (2011)

The hemoglobin threshold at which postoperative red-cell transfusion is warranted is controversial. We conducted a randomized trial to determine whether a higher threshold for blood transfusion would improve recovery in patients who had undergone surgery for hip fracture.
The effect of run and walk exercise programme on blood lipids and chronic inflammation in sedentary males with metabolic syndrome
Authors: Serkan Hazar, Muzaffer Koç, Muhsin Hazar
Journal: British Journal of Sports Medicine (2010)

The aim of the study was to determine and evaluate the effect of 8-week run-walk exercises on blood lipids and chronic inflammation in sedentary males with metabolic syndrome. 13 volunteer males with metabolic syndrome were chosen for the study who applied to participate. Inclusion criteria were diagnostic criteria for metabolic syndrome of National Cholesterol Education Program (ATP III). Blood samples were taken before and after exercise programme. Blood lipids and C reactive protein (CRP) levels were determined by an autoanalyser (Cobas Integra 800; Roche, Mannheim, Germany). Wilcoxon signed rank test was used for data evaluation and significance level α was set at 0.05. Participants performed run and walk for an hour 3 days a week for 8 weeks. In the first week, exercise started for 4 km in an hour, in the later weeks exercise continued for 6 km. After the exercise programme, a significant decrease was observed in the weight, BMI and waist circumference of the participants, whereas the decreases in cholesterol, LDL and triglyceride levels of the participants were statically insignificant. On the other hand, there was statistically significant increase in HDL level. After the exercise programme, decrease of CRP values was statically insignificant. As a result, the 8-week run-walk exercises positively affected some anthropometric characteristics as weight, BMI and waist circumference. But it did not affect blood lipids and chronic inflammation. This exercise was normally expected do make metabolic effect as well as anthropometric effect in a positive way. However, the 8-week run-walk exercise programme can be said to have been not long enough for the participants with metabolic syndrome to make a significant effect.
Plantar Fat-Pad Displacement in Neuropathic Diabetic Patients With Toe Deformity
Authors: Sicco A. Bus, Mario Maas, Peter R. Cavanagh, Robert P. J. Michels, Marcel Levi
Journal: Diabetes Care (2004)

OBJECTIVE—The aim of this study was to quantify the association between claw/hammer toe deformity and changes in submetatarsal head (sub-MTH) fat-pad geometry in diabetic neuropathic feet. RESEARCH DESIGN AND METHODS—Thirteen neuropathic diabetic subjects (mean age 56.2 years) with toe deformity, 13 age- and sex-matched neuropathic diabetic control subjects without deformity, and 13 age- and sex-matched healthy control subjects without deformity were examined. From high-resolution sagittal plane magnetic resonance images of the second and third ray of the foot, toe angle (a measure of deformity), sub-MTH fat-pad thickness, and subphalangeal fat-pad thickness were measured. The ratio of these thicknesses was used to indicate fat-pad displacement. RESULTS—Sub-MTH fat pads were significantly thinner (2.5 ± 1.3 vs. 6.0 ± 1.4 mm, P &amp;lt; 0.001) and subphalangeal fat pads significantly thicker (9.1 ± 1.9 vs. 7.6 ± 1.2 mm, P &amp;lt; 0.005) in the neuropathic group with deformity compared with neuropathic control subjects. As a result, thickness ratio was substantially smaller in the deformity group: 0.28 ± 0.14 vs. 0.79 ± 0.14 in neuropathic control subjects (P &amp;lt; 0.001). A significant correlation of 0.85 was present between toe angle and thickness ratio (P &amp;lt; 0.001). No significant differences were found between neuropathic and healthy control subjects. CONCLUSIONS—This study shows a distal displacement and subsequent thinning of the sub-MTH fat pads in neuropathic diabetic patients with toe deformity and suggests that, as a result, the capacity of the tissue in this region to reduce focal plantar pressure is severely compromised. This condition is likely to increase the risk of plantar ulceration in these patients.
Interleukin-17B Antagonizes Interleukin-25-Mediated Mucosal Inflammation
Authors: Joseph M. Reynolds, Young-Hee Lee, Yun Shi, Xiaohu Wang, Pornpimon Angkasekwinai, Kalyan C. Nallaparaju, Stephanie Flaherty, Seon Hee Chang, Hiroshi Watarai, Chen Dong
Journal: Immunity (2015)
Homeoprotein Signaling in Development, Health, and Disease: A Shaking of Dogmas Offers Challenges and Promises from Bench to Bed
Authors: Julien Spatazza, Elizabeth Di Lullo, Alain Joliot, Edmond Dupont, Kenneth L. Moya, Alain Prochiantz
Journal: Pharmacological Reviews (2013)

Homeoproteins constitute a major class of transcription factors active throughout development and in adulthood. Their membrane transduction properties were discovered over 20 years ago, opening an original field of research in the domain of vector peptides and signal transduction. In early development, homeoprotein transfer participates in tissue patterning, cell/axon guidance, and migration. In the axon guidance model, homeoproteins exert their non–cell autonomous activity through the regulation of translation, in particular, that of nuclear-transcribed mitochondrial mRNAs. An important aspect of these studies on patterning and migration is that homeoproteins sensitize the cells to the action of other growth factors, thus cooperating with established signaling pathways. The role of homeoprotein signaling at later developmental stages is also of interest. In particular, the transfer of homeoprotein Otx2 into parvalbumin-expressing inhibitory neurons (PV-cells) in the visual cortex regulates cortical plasticity. The molecular deciphering of the interaction of Otx2 with binding sites at the surface of PV-cells has allowed the development of a specific Otx2 antagonist that reopens plasticity in the adult cortex and cures mice from experimental amblyopia, a neurodevelopmental disease. Finally, the use of homeoproteins as therapeutic proteins in mouse models of glaucoma and Parkinson disease is reviewed. In the latter case, engrailed homeoproteins protect mesencephalic dopaminergic neurons by increasing the local translation of complex I mitochondrial mRNAs. In conclusion, this review synthesizes 20 years of work on the fundamental and potentially translational aspects of homeoprotein signaling.