tbuckley/cabot-search huggingface dataset:
Oral retinoic acid metabolism blocking agent Rambazole<sup>TM</sup>for plaque psoriasis: an immunohistochemical study
Authors: H.J. Bovenschen, M.E. Otero, A.M.G. Langewouters, I.M.J.J. van Vlijmen-Willems, D.W.A. van Rens, M.M.B. Seyger, P.C.M. van de Kerkhof
Journal: British Journal of Dermatology (2006)

The novel systemic all-trans retinoic acid metabolism blocking agent (RAMBA) R115866 (Rambazole(TM); Barrier Therapeutics, Geel, Belgium; further referred to as rambazole) increases intracellular levels of endogenous all-trans retinoic acid (RA). Well-known effects of RA are normalization of aberrant epithelial growth and differentiation. Hence, rambazole might be beneficial in the treatment of plaque psoriasis.The dynamics of epidermal proliferation, keratinization, lesional T-cell subsets and cells expressing natural killer (NK)-receptors in plaque psoriasis were assessed during treatment with rambazole, as part of a phase IIa open-label clinical trial.Six patients were treated with rambazole, 1 mg, once daily, for 8 weeks. At weeks 0, 2 and 8, psoriatic plaque severity scores (SUM) and biopsies from a target lesion were assessed. Epidermal proliferation (Ki67), keratinization markers (K10, K13, K19), T-cell subsets (CD3, CD4+, CD8+, CD45RO+, CD45RA+, CD2+, CD25+, GITR+) and cells expressing NK-receptors (CD94, CD161) were immunohistochemically stained and quantified with image analysis.At week 2 the mean SUM-score was virtually equal to baseline, which was accompanied immunohistochemically by equal epidermal hyperproliferation, a nonsignificant decrease in K10 positive epidermis and, overall, a nonsignificant increase in immunocyte subsets. At week 8, in contrast, plaque severity was reduced by 34% from baseline (P < 0.05). Improvements were also detected for epidermal proliferation (-63%; P < 0.01) and K10 expression (+29%; P < 0.01), compared with baseline. No induction of retinoid-specific keratinization (K13, K19) was observed. A nonsignificant reduction of all pathogenic T-cell subsets and cells expressing NK-receptors was observed at week 8 of treatment (P > 0.05).Clinical efficacy of rambazole is primarily the result of restoring proliferation (Ki67) and differentiation (K10) of epidermal keratinocytes. Secondly, relevant T-cell subsets and cells expressing NK-receptors showed nonsignificant reductions after 8 weeks of treatment with rambazole.
A different ontogenesis for chronic lymphocytic leukemia cases carrying stereotyped antigen receptors: molecular and computational evidence
Authors: N Darzentas, A Hadzidimitriou, F Murray, K Hatzi, P Josefsson, N Laoutaris, C Moreno, A Anagnostopoulos, J Jurlander, A Tsaftaris, N Chiorazzi, C Belessi, P Ghia, R Rosenquist, F Davi, K Stamatopoulos
Journal: Leukemia (2009)
Physical Activity Energy Expenditure and Glucose Control in Pregnant Women With Type 1 Diabetes
Authors: Kavita Kumareswaran, Daniela Elleri, Janet M. Allen, Karen Caldwell, Kate Westgate, Soren Brage, Philippa Raymond-Barker, Marianna Nodale, Malgorzata E. Wilinska, Stephanie A. Amiel, Roman Hovorka, Helen R. Murphy
Journal: Diabetes Care (2013)

OBJECTIVE To describe activity patterns in pregnant women with type 1 diabetes and evaluate the impact of increased structured physical activity on glucose control. RESEARCH DESIGN AND METHODS Physical activity energy expenditure (PAEE) and glucose levels (continuous glucose monitoring) were measured in 10 pregnant women with type 1 diabetes (age 33.2 years, gestation 20 weeks, BMI 27.9 kg/m2, diabetes duration 16.6 years, HbA1c 6.5% [48 mmol/mol], insulin pump duration 2.4 years) during a day at home (free-living) and during a 24-h visit incorporating controlled diet and structured physical activity with light intensity activity (three 20-min self-paced walks) and moderate intensity activity (two 50-min sessions of brisk treadmill walking). PAEE was evaluated through individually calibrated combined heart rate and movement sensing. RESULTS Free-living PAEE was comparable to that under controlled study conditions (3.8 and 5.1 kcal/kg/day, P = 0.241), with women achieving near to the recommended 30 min of moderate physical activity (median 27 min [interquartile range 14–68]). During the free-living period, more time was spent in light activity (10.3 vs. 7.2 h, P = 0.005), with less sedentary time (13.0 vs. 14.9 h, P = 0.047) and less moderate activity (27 vs. 121 min, P = 0.022). The free-living 24-h mean glucose levels by continuous glucose monitoring were significantly higher (7.7 vs. 6.0 mmol/L, P = 0.028). The effect of controlled diet and exercise persisted overnight, with significantly less time spent hyperglycemic (19 vs. 0%, P = 0.028) and less glucose variability (glucose SD 1.3 vs. 0.7 mmol/L, P = 0.022). CONCLUSIONS A controlled diet and structured physical activity program may assist women with type 1 diabetes in achieving optimal glucose control during pregnancy.
Pain and high sensitivity C reactive protein in patients with chronic low back pain and acute sciatic pain
Authors: T Sturmer
Journal: Annals of the Rheumatic Diseases (2005)

<h3>Objective</h3> This paper draws on the data from the Management and Interventions for Asthma (MIA) study to explore the perceptions and experiences of asthma in British South Asian children using semi-structured interviews. A comparable cohort of White British children was recruited to identify whether any emerging themes were subject to variation between the two groups so that generic and ethnicity-specific themes could be identified for future tailored intervention programmes for South Asian children with asthma. <h3>Setting</h3> South Asian and White British children with asthma took part in semi-structured interviews in Leicester, UK. <h3>Participants</h3> Thirty three South Asian and 14 White British children with asthma and aged 5–12 years were interviewed. <h3>Results</h3> Both similar and contrasting themes emerged from the semi-structured interviews. Interviews revealed considerable similarities in the experience of asthma between the South Asian and White British children, including the lack of understanding of asthma (often confusing trigger with cause), lack of holistic discussions with healthcare professionals (HCPs), an overall neutral or positive experience of interactions with HCPs, the role of the family in children's self-management and the positive role of school and friends. Issues pertinent to South Asian children related to a higher likelihood of feeling embarrassed and attributing physical activity to being a trigger for asthma symptoms. <h3>Conclusions</h3> The two ethnicity-specific factors revealed by the interviews are significant in children's self-management of asthma and therefore, indicate the need for a tailored intervention in South Asian children.
Resting and exercise renal blood flows in immature ovine aortic coarctation. Impact of gradient relief.
Authors: J E Lock, T J Kulik, T P Green, T Niemi, S Einzig
Journal: Circulation Research (1983)

The primary purpose of this study was to determine whether a neonatally induced thoracic aortic coarctation reduces renal blood flow during physiological stress (treadmill exercise), and whether relief of the gradient returned renal blood flow during exercise to normal. Two ancillary questions were also addressed: dose a coarctation after the responses of enteric and other visceral vascular beds to treadmill exercise? Eight newborn lambs that underwent sham thoracotomy with placement of left atrial lines served as controls; in seven lambs we also created a recently described form of dilatable juxtaductal coarctation. This preparation is unique in that, like human coarctation, the obstruction does not get worse as the animal grows. Rest and exercise vascular pressures and regional blood flows were determined 2-2 1/2 months after surgery. Coarctations were relieved with balloon dilation angioplasty catheters, inserted percutaneously. Postdilation rest and exercise hemodynamic studies were performed, at the same level of exercise, 24 hours after dilation. Renal blood flow did not change with exercise in the control animals. In lambs with coarctation, renal blood flow fell (-22%, P less than 0.01) during exercise. Unexpectedly, an exercise-induced fall in renal blood flow (-22%, P less than 0.001) persisted even after effective relief of the coarctation (descending aortic blood pressure fell 25% with exercise predilation, but remained unchanged with exercise postdilation). Blood flow to the terminal ileum and cecum followed a qualitatively similar pattern to that of renal blood flow in control, predilation, and postdilation lambs, and this pattern was distinct from that of other enteric and visceral organ flows. These results demonstrate an expected abnormality in the regulation of exercise renal blood flow in lambs with coarctation of the aorta; however, the persistence of this abnormality after effective gradient relief does not support the previously advanced theory that postcoarctation hypertension is largely nonrenal in origin. The apparent similarity between ileocecal and renal blood flow control under these circumstances may provide a clue to the known predilection of the terminal ileum to suffer ischemic injury.
Follicle-Stimulating Hormone Peptide Can Facilitate Paclitaxel Nanoparticles to Target Ovarian Carcinoma <i>In vivo</i>
Authors: Xiao-yan Zhang, Jun Chen, Yu-fang Zheng, Xiao-ling Gao, Yu Kang, Jia-chi Liu, Ming-jun Cheng, Hong Sun, Cong-jian Xu
Journal: Cancer Research (2009)

Chemotherapy is an important treatment for ovarian cancer. However, conventional chemotherapy has inevitable drawbacks due to side effects from nonspecific biodistribution of the chemotherapeutic drugs. To solve such problem, targeted delivery approaches were developed. The targeted delivery approaches combine drug carriers with the targeting system and can preferentially bring drugs to the targeted sites. Follicle-stimulating hormone receptor (FSHR) is an ovarian cancer-specific receptor. By using a peptide derived from FSH (amino acids 33-53 of the FSH beta chain, named as FSH33), we developed a conjugated nanoparticle, FSH33-NP, to target FSHR in ovarian cancer. FSH33-NP was tested for recognition specificity and uptake efficiency on FSHR-expressing cells. Then, the antitumor efficiency of paclitaxel (PTX)-loaded FSH33-NP (FSH33-NP-PTX) was determined. FSH33-NP-PTX displayed stronger antiproliferation and antitumor effects compared with free PTX or naked PTX-loaded nanoparticles (NP-PTX) both in vitro and in vivo. In summary, this novel FSH33-NP delivery system showed very high selectivity and efficacy for FSHR-expressing tumor tissues. Therefore, it has good potential to become a new therapeutic approach for patients with ovarian cancer.
Histoplasmosis Relapse in Patients with AIDS: Detection Using <i>Histoplasma capsulatum</i> variety <i>capsulatum</i> Antigen Levels
Authors: L J Wheat, P Connolly-Stringfield, R Blair, K Connolly, T Garringer, B P Katz
Journal: Annals of Internal Medicine (1991)

Objective: To assess the accuracy of Histoplasma capsulatum variety capsulatum polysaccharide antigen testing for the identification of histoplasmosis relapse in patients with the acquired immunodeficiency syndrome (AIDS). Design: A retrospective study using stored specimens. Setting: A referral center and several private hospitals. Patients: Twenty episodes of histoplasmosis relapse were evaluated in 17 patients with AIDS from November 1987 to August 1990. Controls included 30 patients with AIDS and histoplasmosis who did not have a relapse during maintenance therapy and who were initially tested during the same week as the patients with relapse. A second control group included seven patients with AIDS and histoplasmosis who were evaluated for relapse on 23 occasions; relapse, however, was excluded on each occasion. Measurements: To avoid interassay variability, specimens were tested for H.c. var. capsulatum polysaccharide antigen with the same radioimmunoassay. Main Outcome Measure: The change in the H.c. var. capsulatum polysaccharide antigen level during successful as opposed to unsuccessful maintenance therapy for the prevention of histoplasmosis relapse. Main Results: For the 20 episodes of relapse (17 patients), H.c. var. capsulatum antigen levels increased by at least 2 radioimmunoassay units in 12 of 14 serum specimens tested (85.7%; 95% Cl, 57.2% to 98.2%) and in 17 of 18 urine specimens tested (94.4%; Cl, 72.7% to 99.9%). Antigen levels increased in the urine or serum in 1 of 83 specimens (1.2%; Cl, 0.03% to 6.6%) obtained on 56 occasions (1.8%; Cl, 0.04% to 9.6%) from controls (specificity, 98.2%; Cl, 90.4% to 99.96%). In three cases of relapse, antigen levels increased before clinical relapse was suspected. Complement fixation titers increased by at least 2 dilutions in 4 of 11 cases (36.4%; Cl, 10.9% to 69.2%) but in 0 of 9 control patients (Cl, 0% to 28.3%). Conclusion: An increase in H.c. var. capsulatum polysaccharide antigen levels of 2 units or more strongly suggests histoplasmosis relapse. The presence of increasing titers of anti-H.c. var. capsulatum antibodies by complement fixation is less accurate for the diagnosis of relapse.
Tumor-Specific Gene Delivery Using Recombinant Vaccinia Virus in a Rabbit Model of Liver Metastases
Authors: M F Gnant, L A Noll, K R Irvine, M Puhlmann, R E Terrill, H R Alexander, D L Bartlett
Journal: JNCI Journal of the National Cancer Institute (1999)

BACKGROUND: Several approaches to gene therapy for cancer have yielded promising results in rodent models. The translation of these results to the clinical realm has been delayed by the lack of tumor models in large animals. We investigated the pattern of transgene (i.e., foreign or introduced gene) expression and virus vector elimination after systemic gene delivery using a thymidine kinase-negative vaccinia virus in a rabbit model of disseminated liver metastases. METHODS: VX-2 rabbit carcinoma cells were maintained by serial transplantation in the thigh muscles of New Zealand White rabbits, and disseminated liver metastases were established by direct injection of tumor cells into the portal vein of the animals. Different doses of a recombinant thymidine kinase-negative vaccinia virus vector encoding the firefly luciferase reporter gene (i.e., transgene) were injected into tumor-bearing rabbits. Transgene activity in tumors and other organs was measured at multiple time points thereafter. The pattern of development of antibodies against the vaccinia virus vector was also examined. Two-tailed Student's paired t test was used for comparisons of transgene activity. RESULTS: Transgene expression was increased in tumors by at least 16-fold in comparison with expression in other tissues by day 4 after vector injection (all P <.001) and was maintained for approximately 1 week, providing evidence of tumor-specific gene delivery in this model. Rapid elimination of the circulating vector by the host immune system was observed. Anti-vector antibodies were detectable in serum as early as day 6 and were maintained for more than 3 months. CONCLUSIONS: Tumor-specific gene delivery is possible after systemic injection of a thymidine kinase-negative vaccinia virus vector in a model of rabbit liver metastases. Although the period of transgene expression appears limited because of a rapid immune response, the therapeutic window might be sufficient for an enzyme/prodrug gene therapy approach in clinical application.
Supplemental Oxygen Prevents Exercise-induced Oxidative Stress in Muscle-wasted Patients with Chronic Obstructive Pulmonary Disease
Authors: Hanneke A. C. van Helvoort, Yvonne F. Heijdra, Leo M. A. Heunks, Patty L. M. Meijer, Wim Ruitenbeek, Hub M. H. Thijs, P. N. Richard Dekhuijzen
Journal: American Journal of Respiratory and Critical Care Medicine (2006)

Although oxygen therapy is of clear benefit in patients with severe chronic obstructive pulmonary disease (COPD), recent studies have shown that short-term supplementary oxygen may increase oxidative stress and inflammation within the airways.We investigated whether systemic inflammation and oxidative stress at rest and during exercise in patients with COPD are influenced by supplemental oxygen.Nine normoxemic, muscle-wasted patients with moderate to very severe COPD were studied. Plasma markers of systemic inflammation (leukocyte counts, interleukin 6 [IL-6]) and oxidative stress (lipid peroxidation, protein oxidation, antioxidant capacity) were measured after treatment with either supplemental oxygen (nasal, 4 L . min(-1)) or compressed air, both at rest (1 h treatment) and after submaximal exercise (40 W, constant work rate). In addition, free-radical production by neutrophils and ATP-degradation products were determined before and after exercise.Short-term oxygen breathing at rest did not influence systemic low-grade inflammation and oxidative stress. The IL-6 response to exercise was attenuated during cycling with supplemental oxygen. Exercise-induced lipid and protein oxidation were prevented by treatment with supplemental oxygen. This was associated with both decreased free-radical production by neutrophils and reduced formation of (hypo)xanthine and uric acid.Short-term supplementary oxygen does not affect basal systemic inflammation and oxidative stress but prevents exercise-induced oxidative stress in normoxemic, muscle-wasted patients with COPD, and attenuates plasma IL-6 response. Inhibition of neutrophil activation and ATP degradation appears to be involved in this effect.
Cisplatin Decreases the Abundance of Aquaporin Water Channels in Rat Kidney
Authors: SOO-WAN KIM, JONG-UN LEE, MYONG-YUN NAH, DAE-GILL KANG, KYU-YOUN AHN, HO-SUB LEE, KI-CHUL CHOI
Journal: Journal of the American Society of Nephrology (2001)

The present study examined whether the cisplatin induced urinary concentration defect can be related to an altered regulation of aquaporin (AQP) water channels in the kidney. Cisplatin (8 mg/kg) was injected intraperitoneally into male Sprague-Dawley rats. The control group was without cisplatin treatment. Four d later, the expression of AQP1, AQP2, and AQP3 proteins was determined in the kidney. To specify further the primary point of derangement in the pathway that activates the arginine vasopressin-mediated AQP channels, different components of adenylyl cyclase complex were examined separately. The cisplatin treatment caused a polyuric renal failure in association with decreases of free water reabsorption. The expression of AQP1 and AQP2 was decreased in the cortex, the outer medulla, and the inner medulla, whereas that of AQP3 was decreased in the outer medulla and the inner medulla. The expression of AQP2 proteins in the apical membrane-enriched fraction decreased in parallel with that in the subapical vesicle-enriched fraction, indicating a preserved targeting. Immunohistochemistry of the outer medulla also revealed that cisplatin decreased immunoreactivity for AQP1, AQP2, and AQP3. The arginine vasopressin-evoked generation of cyclic adenosine monophosphate was attenuated by cisplatin, being most prominent in the outer medulla. However, the cyclic adenosine monophosphate generation in response to forskolin was not affected, whereas that to sodium fluoride was diminished significantly. Cisplatin also decreased the expression of Gsalpha proteins in the outer medulla and the inner medulla. These results suggest that a reduced expression of AQP water channels accounts at least in part for the cisplatin-induced urinary concentration defect.
Daily Activity Energy Expenditure and Mortality Among Older Adults
Authors: Todd M. Manini, James E. Everhart, Kushang V. Patel, Dale A. Schoeller, Lisa H. Colbert, Marjolein Visser, Frances Tylavsky, Douglas C. Bauer, Bret H. Goodpaster, Tamara B. Harris
Journal: JAMA (2006)

Exercise is associated with mortality benefits but simply expending energy through any activity in an individual's free-living environment may confer survival advantages.To determine whether free-living activity energy expenditure is associated with all-cause mortality among older adults.Free-living activity energy expenditure was assessed in 302 high-functioning, community-dwelling older adults (aged 70-82 years). Total energy expenditure was assessed over 2 weeks using doubly labeled water. Resting metabolic rate was measured using indirect calorimetry and the thermic effect of meals was estimated at 10% of total energy expenditure. Free-living activity energy expenditure was calculated as: (total energy expenditure x 0.90) - resting metabolic rate. Participants were followed up over a mean of 6.15 years (1998-2006).Free-living activity energy expenditure (3 tertiles: low, <521 kcal/d; middle, 521-770 kcal/d; high, >770 kcal/d) and all-cause mortality.Fifty-five participants (18.2%) died during follow-up. As a continuous risk factor, an SD increase in free-living activity energy expenditure (287 kcal/d) was associated with a 32% lower risk of mortality after adjusting for age, sex, race, study site, weight, height, percentage of body fat, and sleep duration (hazard ratio, 0.68; 95% confidence interval, 0.48-0.96). Using the same adjustments, individuals in the highest tertile of free-living activity energy expenditure were at a significantly lower mortality risk compared with the lowest tertile (hazard ratio, 0.31; 95% confidence interval, 0.14-0.69). Absolute risk of death was 12.1% in the highest tertile of activity energy expenditure vs 24.7% in the lowest tertile; absolute risks were similar to these for tertiles of physical activity level. The effect of free-living activity energy expenditure changed little after further adjustment for self-rated health, education, prevalent health conditions, and smoking behavior. According to self-reports, individuals expending higher levels of free-living activity energy were more likely to work for pay (P = .004) and climb stairs (P = .01) but self-reported high-intensity exercise, walking for exercise, walking other than for exercise, volunteering, and caregiving did not differ significantly across the activity energy expenditure tertiles.Objectively measured free-living activity energy expenditure was strongly associated with lower risk of mortality in healthy older adults. Simply expending energy through any activity may influence survival in older adults.