tbuckley/cabot-search huggingface dataset:
Chronic Multisymptom Illness Affecting Air Force Veterans of the Gulf War
Authors: K Fukuda, R Nisenbaum, G Stewart, W W Thompson, L Robin, R M Washko, D L Noah, D H Barrett, B Randall, B L Herwaldt, A C Mawle, W C Reeves
Journal: JAMA (1998)

Context.—Gulf War (GW) veterans report nonspecific symptoms significantly more often than their nondeployed peers. However, no specific disorder has been identified, and the etiologic basis and clinical significance of their symptoms remain unclear.Objectives.—To organize symptoms reported by US Air Force GW veterans into a case definition, to characterize clinical features, and to evaluate risk factors.Design.—Cross-sectional population survey of individual characteristics and symptoms and clinical evaluation (including a structured interview, the Medical Outcomes Study Short Form 36, psychiatric screening, physical examination, clinical laboratory tests, and serologic assays for antibodies against viruses, rickettsia, parasites, and bacteria) conducted in 1995.Participants and Setting.—The cross-sectional questionnaire survey included 3723 currently active volunteers, irrespective of health status or GW participation, from 4 air force populations.The cross-sectional clinical evaluation included 158 GW veterans from one unit, irrespective of health status.Main Outcome Measures.—Symptom-based case definition; case prevalence rate for GW veterans and nondeployed personnel; clinical and laboratory findings among veterans who met the case definition.Results.—We defined a case as having 1 or more chronic symptoms from at least 2 of 3 categories (fatigue, mood-cognition, and musculoskeletal). The prevalence of mild-to-moderate and severe cases was 39% and 6%, respectively, among 1155 GW veterans compared with 14% and 0.7% among 2520 nondeployed personnel. Illness was not associated with time or place of deployment or with duties during the war. Fifty-nine clinically evaluated GW veterans (37%) were noncases, 86 (54%) mild-to-moderate cases, and 13 (8%) severe cases. Although no physical examination, laboratory, or serologic findings identified cases, veterans who met the case definition had significantly diminished functioning and well-being.Conclusions.—Among currently active members of 4 Air Force populations, a chronic multisymptom condition was significantly associated with deployment to the GW. The condition was not associated with specific GW exposures and also affected nondeployed personnel.
Globular Adiponectin Enhances Muscle Insulin Action via Microvascular Recruitment and Increased Insulin Delivery
Authors: Lina Zhao, Weidong Chai, Zhuo Fu, Zhenhua Dong, Kevin W. Aylor, Eugene J. Barrett, Wenhong Cao, Zhenqi Liu
Journal: Circulation Research (2013)

Rationale: Adiponectin enhances insulin action and induces nitric oxide–dependent vasodilatation. Insulin delivery to muscle microcirculation and transendothelial transport are 2 discrete steps that limit insulin’s action. We have shown that expansion of muscle microvascular surface area increases muscle insulin delivery and action. Objective: To examine whether adiponectin modulates muscle microvascular recruitment thus insulin delivery and action in vivo. Methods and Results: Overnight fasted adult male rats were studied. We determined the effects of adiponectin on muscle microvascular recruitment, using contrast-enhanced ultrasound, on insulin-mediated microvascular recruitment and whole-body glucose disposal, using contrast-enhanced ultrasound and insulin clamp, and on muscle insulin clearance and uptake with 125 I-insulin. Globular adiponectin potently increased muscle microvascular blood volume without altering microvascular blood flow velocity, leading to a significantly increased microvascular blood flow. This was paralleled by a ≈30% to 40% increase in muscle insulin uptake and clearance, and ≈30% increase in insulin-stimulated whole-body glucose disposal. Inhibition of endothelial nitric oxide synthase abolished globular adiponectin-mediated muscle microvascular recruitment and insulin uptake. In cultured endothelial cells, globular adiponectin dose-dependently increased endothelial nitric oxide synthase phosphorylation but had no effect on endothelial cell internalization of insulin. Conclusions: Globular adiponectin increases muscle insulin uptake by recruiting muscle microvasculature, which contributes to its insulin-sensitizing action.
Farber's lipogranulomatosis in siblings: light and electron microscopic studies
Authors: M. CHANOKI, M. ISHII, K. FUKAI, H. KOBAYASHI, T. HAMADA, K. MURAKAMI, A. TANAKA
Journal: British Journal of Dermatology (1989)

Journal Article Farber's lipogranulomatosis in siblings: light and electron microscopic studies Get access M. CHANOKI, M. CHANOKI Department of Dermatology, Osaka City University Medical School Dr M.Chanoki, Department of Dermatology, Osaka City University Medical School, 1‐5‐7 Asahimachi, Abeno‐ku, Osaka 545, Japan. Search for other works by this author on: Oxford Academic Google Scholar M. ISHII, M. ISHII Department of Dermatology, Osaka City University Medical School Search for other works by this author on: Oxford Academic Google Scholar K. FUKAI, K. FUKAI Department of Dermatology, Osaka City University Medical School Search for other works by this author on: Oxford Academic Google Scholar H. KOBAYASHI, H. KOBAYASHI Department of Dermatology, Osaka City University Medical School Search for other works by this author on: Oxford Academic Google Scholar T. HAMADA, T. HAMADA Department of Dermatology, Osaka City University Medical School Search for other works by this author on: Oxford Academic Google Scholar K. MURAKAMI, K. MURAKAMI Division of Dermatology, Osaka Municipal Kita Hospital Search for other works by this author on: Oxford Academic Google Scholar A. TANAKA A. TANAKA Department of Pediatrics, Osaka City University Medical School, Osaka, Japan Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 121, Issue 6, 1 December 1989, Pages 779–785, https://doi.org/10.1111/j.1365-2133.1989.tb08222.x Published: 01 December 1989
HSPA12B attenuates cardiac dysfunction and remodelling after myocardial infarction through an eNOS-dependent mechanism
Authors: Jingjin Li, Yangyang Zhang, Chuanfu Li, Jian Xie, Ying Liu, Weina Zhu, Xiaojin Zhang, Surong Jiang, Li Liu, Zhengnian Ding
Journal: Cardiovascular Research (2013)

HSPA12B is a newly discovered and endothelial-cell-specifically expressed heat shock protein. We have reported recently that overexpression of HSPA12B increased endothelial nitric oxide synthase (eNOS) expression in mouse cardiac tissues during endotoxemia. Endothelial NOS has been shown to protect heart from ischaemic injury. We hypothesized that overexpression of HSPA12B will attenuate cardiac dysfunction and remodelling after myocardial infarction (MI) through an eNOS-dependant mechanism. MI was induced by permanent ligation of the left anterior descending coronary artery in the transgenic mice (Tg) overexpressing hspa12b gene and its wild-type (WT) littermates. Echocardiographic analysis revealed that Tg mice exhibited improvements in cardiac dysfunction and remodelling at 1 and 4 weeks after MI. These improvements were accompanied by a significant decrease in cardiomyocyte apoptosis and increase in capillary and arteriolar densities. Significant up-regulation of eNOS, VEGF, Ang-1, and Bcl-2 was also observed in Tg hearts compared with WT hearts after MI. However, pharmacological inhibition of eNOS abolished the HSPA12B-induced decrease in cardiomyocyte apoptosis and increase in capillary formation after MI. Most importantly, inhibition of eNOS abrogated the protection of HSPA12B against cardiac dysfunction and remodelling after MI. These data demonstrate for the first time that the overexpression of HSPA12B attenuates cardiac dysfunction and remodelling after MI. This action of HSPA12B was mediated, at least in part, by prevention of cardiomyocyte apoptosis and promotion of myocardial angiogenesis via an eNOS-dependent mechanism. HSPA12B could be a novel target for the management of patients with post-MI cardiac dysfunction and remodelling.
Sphingomyelinase and Membrane Sphingomyelin Content
Authors: RICHARD A. ZAGER, KRISTIN M. BURKHART, ALI JOHNSON
Journal: Journal of the American Society of Nephrology (2000)

Abstract. Ceramides acutely accumulate in proximal tubules during injury. Pathogenic relevance of this change is suggested by observations that adding ceramide to tubular cells alters superimposed hypoxic and toxic attack. Ceramide accumulation during cell injury is thought to arise from sphingomyelinase (SMase)-mediated sphingomyelin (SM) hydrolysis ± decreased catabolism. Thus, ceramide addition to cells cannot precisely simulate pathophysiologic events. Therefore, this study assessed direct effects of SMase activity on tubular cell viability under basal conditions and during superimposed attack. Cultured human proximal tubule (HK-2) cells were exposed to differing SMase doses. Its effects on cell phospholipids, ceramides, proliferation rates, and susceptibility to injury (ATP depletion, Fe-mediated oxidant stress) were assessed. Because SMase reduces cell SM content, the effect of exogenous SM on membrane injury (intact cells, isolated vesicles) was also tested. Finally, because SM decreases membrane fluidity, the impact of a fluidizing agent (A 2 C) on membrane injury (phospholipase A 2 , lipid peroxidation) was addressed. SMase reduced HK-2 SM content by approximately 33%, but only modest ceramide increments resulted (suggesting high endogenous ceramidase activity). SMase, by itself, caused no cell death (lactate dehydrogenase release). However, it was mildly antiproliferative, and it dramatically predisposed to both ATP depletion- and Fe-mediated attack. SMase also predisposed isolated vesicles to damage, suggesting that its impact on intact cells reflects a direct membrane effect. Adding SM to intact cells (or vesicles) mitigated ATP depletion and Fe- and phospholipase A 2 -induced damage. In contrast, A 2 C rendered membranes more vulnerable to attack. SMase predisposes tubular cells to superimposed ATP depletion and oxidant injury. This may be explained by SM losses, and not simply cytotoxic ceramide gains, given that SM can directly decrease cell/membrane damage. The ability of SM to decrease membrane fluidity may explain, at least in part, its cytoprotective effect.
Health Status After Treatment for Coronary Artery Disease and Type 2 Diabetes Mellitus in the Bypass Angioplasty Revascularization Investigation 2 Diabetes Trial
Authors: Maria Mori Brooks, Sheng-Chia Chung, Tarek Helmy, William B. Hillegass, Jorge Escobedo, Kathryn A. Melsop, Elaine M. Massaro, Robert D. McBane, Pamela Hyde, Mark A. Hlatky
Journal: Circulation (2010)

Background— Health status is a key outcome for comparing treatments, particularly when mortality does not differ significantly. Methods and Results— Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) randomized 2368 patients with type 2 diabetes mellitus and stable ischemic heart disease to (1) prompt revascularization versus medical therapy and (2) insulin sensitization versus insulin provision. Randomization was stratified by the intended method of revascularization, coronary artery bypass graft surgery or percutaneous coronary intervention. The Duke Activity Status Index and RAND Energy, Health Distress, and Self-Rated Health scales were assessed at study entry and annually thereafter; linear mixed models were used to evaluate the effect of randomized treatment on these measures. Health status improved significantly from baseline to 1 year ( P &lt;0.001) in each randomized treatment group. Compared with medical therapy, prompt revascularization was associated with significantly greater improvements in Duke Activity Status Index (1.32 points; P &lt;0.001), Energy (1.36 points; P =0.02), and Self-rated Health (1.77 points; P =0.007) but not Health Distress (−0.47; P =0.46). These treatment effects were largely maintained over 4 years of follow-up. The effect of revascularization on the Duke Activity Status Index was significantly larger in the subgroup of patients intended for coronary artery bypass graft surgery compared with the subgroup intended for percutaneous coronary intervention. Health status did not differ significantly on any of the 4 measures between the insulin provision and insulin sensitization strategies. Conclusions— Prompt coronary revascularization was associated with small yet statistically significant improvements in health status compared with initial medical therapy among patients with diabetes mellitus and stable ischemic heart disease. Clinical Trial Registration— http://www.clinicaltrials.gov . Unique identifier: NCT00006305.
Direct evidence of estrogen modulation of pituitary sensitivity to luteinizing hormone-releasing factor during the menstrual cycle.
Authors: C F Wang, S S Yen
Journal: Journal of Clinical Investigation (1975)

To delineate the role of estradiol in the augmented pituitary gonadotropin responsiveness to synthetic luteinizing hormone releasing factor (LRF) seen during high-estrogen phases of the ovulatory cycles (late follicular and midluteal phases), the anti-estrogenic effect of clomiphene citrate (Clomid) on pituitary response to LRF was evaluated during different phases of the ovulatory cycle. Clomid administration (100 mg/day times 5 days) completely negates the augmented gonadotropin responses to LRF (150 mug) during late follicular and midluteal phases observed during the control studies. Thus, a quantitatively and qualitatively similar pituitary sensitivity to LRF during three distinct phases of the menstrual cycle was induced by Clomid treatment that resembles the LRF responsiveness of themale pituitary. The present study demonstrates the pituitary component of the estrogen-induced changes in the sensitivity to LRF. From this and previous data, we conclude that the increases of estradiol secretion associated with the follicular maturation and corpus luteum formation represent a major component of the feedback signal in the modulation of cyclic gonadotropin release occasioned in a large measure by the augmented pituitary sensitivity to LRF.
cGMP-Dependent Protein Kinase Regulation of the L-Type Ca <sup>2+</sup> Current in Rat Ventricular Myocytes
Authors: Kotaro Sumii, Nicholas Sperelakis
Journal: Circulation Research (1995)

Abstract Regulation of L-type Ca 2+ channel current [I Ca(L) ] by cGMP-dependent protein kinase (PK-G) was investigated in ventricular myocytes from 2- to 21-day-old rats using whole-cell voltage clamp with internal perfusion. I Ca(L) was elicited by a depolarizing pulse to +10 mV from a holding potential of −40 mV. Stimulated I Ca(L) (by 2 μmol/L isoproterenol) was inhibited to the basal level by internal perfusion with 50 nmol/L PK-G (activated by 8Br-cGMP, 0.1 μmol/L). When I Ca(L) was enhanced by Bay K 8644 (1 μmol/L), the enhanced basal I Ca(L) was also reduced by PK-G. Basal I Ca(L) (nonstimulated through the cAMP/cAMP-dependent protein kinase [PK-A] pathway) was also inhibited to various degrees (large, medium, or small) by internal application of PK-G (25 nmol/L). The average inhibition was 42.1% (n=36), and there were no differences in the inhibition during development. The inhibition by PK-G was blocked by the PK-G substrate peptide (cG-PKI, 300 μmol/L) and by heat inactivation of the PK-G. Relatively specific PK-G inhibitors (eg, cG-PKI and H-8) sometimes reversed the inhibition (5 of 25 cells), whereas isoproterenol stimulated I Ca(L) (7 of 8 cells). When a holding potential of −80 mV was used, the inhibition produced by PK-G was much less. The inhibitory effects of PK-G were not mediated by activating phosphodiesterase or protein phosphatase but most likely by a direct phosphorylation of the Ca 2+ channel or associated regulatory protein. The inhibitory effect of PK-G may be explained by a balance between activities of PK-A and PK-G in regulating the slow Ca 2+ channels at two separate sites.
Normal regional distribution of membrane current density in rat left ventricle is altered in catecholamine-induced hypertrophy
Authors: S Bryant
Journal: Cardiovascular Research (1999)

Objective: To test the hypothesis that changes in the normal regional distribution of potassium and calcium currents contribute to the different regional changes in action potential duration in isoprenaline-induced hypertrophy in rats. Methods: Hypertrophy was elicited in rats by seven daily injections of isoprenaline. Left ventricular myocytes were isolated from basal sub-endocardial, basal mid-myocardial and apical sub-epicardial tissue. Membrane currents were measured using the whole-cell patch-clamp technique at 35±1°C. Results: Cell membrane capacitance was similar in all three groups and was increased by 17% in hypertrophy (P<0.001, t-test). Changes in the calcium-independent transient outward current (Ito1) density in hypertrophy were different in the three regions (P<0.05, ANOVA). Ito1 was reduced in sub-epicardial (control, 23.4±2.0 pA pF−1; hypertrophy, 15.8±1.5 pA pF−1, P<0.01 ANOVA) and in mid-myocardial myocytes (control, 24.0±2.8 pA pF−1; hypertrophy, 13.8±1.3 pA pF−1, P<0.01 ANOVA) and was not significantly altered in sub-endocardial myocytes (control, 8.5±0.7 pA pF−1; hypertrophy, 7.4±1.8 pA pF−1). Steady-state background current density was reduced in hypertrophy (P<0.05, ANOVA). The regional difference in steady-state background current in control hearts (P<0.05, ANOVA) was altered in hypertrophy. Calcium current (ICa) density was similar in the three regions studied in both control and hypertrophied hearts. ICa was reduced in hypertrophy (P<0.05, ANOVA). Conclusion: The normal regional differences in Ito1 are reduced, in steady-state background current are altered and in ICa are unchanged in catecholamine-induced hypertrophy in the rat left ventricle. These data may in part explain the reduction in the normal regional differences in APD observed in hypertrophy.
SYNTHESIS OF PLASMA MEMBRANE-ASSOCIATED AND SECRETORY IMMUNOGLOBULIN IN DIPLOID LYMPHOCYTES
Authors: Richard A. Lerner, Patricia J. McConahey, Inga Jansen, Frank J. Dixon
Journal: The Journal of Experimental Medicine (1972)

The half disappearance time for detectable plasma membrane-associated and cytoplasmic immunoglobulin after treatment of continuously growing diploid lymphocytes with inhibitors of protein and RNA synthesis was studied. Also, the amount of plasma membrane-associated and cytoplasmic immunoglobulin of synchronized cells in the G(1) phase of the cell cycle has been studied. Plasma membrane-associated immunoglobulin has a half disappearance time of 45 min after inhibition of protein synthesis. By contrast, after treatment of cells with actinomycin D for 24 hr, plasma membrane-associated immunoglobulin remains relatively unchanged whereas cytoplasmic immunoglobulin decreased by almost 90%. In the G(1) phase of the cell cycle, plasma membrane-associated immunoglobulin and cytoplasmic immunoglobulin were 70 and 10%, respectively, of that in logarithmically growing cells, and the half disappearance of M-Ig after treatment of cells with puromycin was again 45 min. In toto, these results suggest that perhaps secreted and plasma membrane-associated immunoglobulin may be separately controlled by the cells.
Day 15 peripheral blood lymphocyte/monocyte ratio post-autologous peripheral hematopoietic stem cell transplantation and survival in diffuse large B-cell lymphoma.
Authors: L. F. Porrata, D. J. Inwards, S. M. Ansell, I. N. M. Micallef, P. B. Johnston, W. J. Hogan, S. Markovic
Journal: Journal of Clinical Oncology (2011)

8018 Background: Day 15 absolute lymphocyte count (ALC-15) post-autologous peripheral hematopoietic stem cell transplantation (APHSCT) is a prognostic factor for survival. Monocyte-derived cells affect tumor growth by suppression of host anti-tumor immunity and promotion of tumor angiogenesis (tumor microenvironment). Thus, we set out to investigate if the absolute lymphocyte count/absolute monocyte count ratio at day 15 (ALC/AMC-15 ratio), as a simple biomarker of host immunity and tumor microenvironment, affects survival post-APHSCT. Methods: From 1994 to 2007, 256 consecutive diffuse large B-cell lymphoma (DLBCL) patients that underwent APHSCT were studied. Results: The median follow-up for the cohort was 2.8 years (range: 0.1-17 years). Patients with an ALC/AMC-15 ratio ≥1 experienced a superior overall survival (OS) compared with patients with an ALC/AMC-15 < 1 post-APHSCT (median OS was not reached vs 9.9 months, 5-year OS rates of 86% vs 16%, p < 0.0001, respectively). Progression-free survival (PFS) was also superior if the ALC/AMC-15 ratio was ≥ 1 vs < 1 (median PFS was 197 months vs 4.4 months, 5-year PFS rates of 83% vs 10%, p < 0.0001, respectively). Multivariate analysis showed ALC/AMC-15 ratio to be an independent prognostic factor for OS and PFS post-APHSCT. Conclusions: ALC/AMC-15 ratio is associated with clinical outcomes post-APHSCT in DLBCL patients and warrants further studies.
Direct and antibody dependent cell mediated cytotoxicity against Giardia lamblia by splenic and intestinal lymphoid cells in mice.
Authors: S S Kanwar, N K Ganguly, B N Walia, R C Mahajan
Journal: Gut (1986)

Direct cytotoxicity and antibody dependent cell mediated cytotoxicity against Giardia lamblia trophozoites exhibited by splenic, intraepithelial and lamina propria lymphocyte populations isolated from G lamblia infected mice were studied. Different patterns of cytotoxicity were found. Intraepithelial lymphocytes showed a direct cytotoxic activity of 20.6 +/- 5.6% before infection. It was significantly higher on the 20th (p less than 0.01) and 30th (p less than 0.05) day postinfection. Lamina propria lymphocytes showed a significantly augmented level of both direct cytotoxicity and antibody dependent cell mediated cytotoxicity on the 20th and 30th postinfection days. Direct cytotoxicity by splenic lymphocytes remained unchanged during infection but antibody dependent cell mediated cytotoxicity was significantly increased.
Choosing the surgical mortality threshold for high risk patients with stage Ia non-small cell lung cancer: insights from decision analysis
Authors: J Dowie
Journal: Thorax (2002)

The recent British Thoracic Society guidelines recommend that surgical mortality should not be greater than 8% for pneumonectomy and 4% for lobectomy. These cut offs are advanced as guidelines to inform decision making as to whether or not patients with operable lung cancer should be offered surgery. They have been developed from a notion of what acceptable surgical mortality should be. The planning of care for patients with lung cancer involves making choices between different treatments with different outcomes. While it is accepted that the probability of these outcomes is likely to differ among patients, individual patient preferences for them are also likely to vary. Fixed cut offs for surgical mortality mean ignoring this variation. Decision analysis can be used to assist in the complex task of integrating clinical characteristics and varying patient preferences. By considering high risk patients with potentially curable stage Ia non-small cell lung cancer, it is shown that decision analysis has the potential to illuminate decision making and guideline development within the field of cancer care.