tbuckley/cabot-search huggingface dataset:
Cyclosporine A Suppresses Cyclooxygenase-2 Expression in the Rat Kidney
Authors: Klaus Ho[Combining Diaeresis]cherl, Franziska Dreher, Helga Vitzthum, Jens Ko[Combining Diaeresis]hler, Armin Kurtz
Journal: Journal of the American Society of Nephrology (2002)

ABSTRACT. On the basis of recent evidence that the cyclooxygenase-2 (COX-2) gene promoter contains functional binding sites for the nuclear factor of activated T cells (NFAT) and that COX-2 is expressed in a regulated fashion in the kidney, this study aimed to assess the effect of immunosuppressants on COX-2 expression in the kidney. Therefore, Wistar-Kyoto rats were treated with cyclosporine A (CsA; 15 mg/kg per day) or tacrolimus (5 mg/kg per day) for 7 d each. Both drugs markedly lowered COX-2 expression while COX-1 expression remained unaltered. Furthermore, CsA blunted the increase of renocortical COX-2 expression in response to low salt intake or a combination of low-salt diet with the ACE inhibitor ramipril (10 mg/kg per day), which strongly stimulates renocortical COX-2 expression. At the same time, calcineurin inhibitors moderately enhanced basal as well as stimulated renin secretion and renin gene expression. These findings suggest that inhibition of calcineurin could be a crucial determinant for the regulated expression of COX-2 in the kidney. Inhibition of COX-2 expression may therefore at least in part account for the well-known adverse effects of immunosuppressants in the kidney. Moreover, our data suggest that the stimulation of the renin system by low salt and by ACE inhibitors is not essentially mediated by COX-2 activity. E-mail: [email protected]
THE INTERACTION OF HOST AND BACTERIUM IN THE DEVELOPMENT OF COMMUNICABILITY BY STREPTOCOCCUS HAEMOLYTICUS
Authors: Alvin F. Coburn, Ruth H. Pauli
Journal: The Journal of Experimental Medicine (1941)

An epidemic of infections due to group A Streptococcus haemolyticus type 12 originated in an infant with bronchiectasis, and involved children and nurses. Some of the children spread contagion; the nurses did not spread contagion. The children who spread contagion had few or no recognizable type 12 organisms in their throats; most of the nurses had type 12 predominant in their throat flora. Two children who spread contagion had non-hemolytic streptococci in their throat flora, which became hemolytic on cultivation and proved to be type 12. Four children had in their throat flora hemolytic type 12 streptococci which became non-hemolytic when grown in fluid media containing serum. These infants appeared to act as disseminating hosts in which the pathogen developed communicability and at the same time became morphologically and physiologically labile. The labile streptococci gave rise to atypical forms whose requirements for rapid reproduction (as tested in vitro) were similar to those existing in the human host. The hypothesis presented is that the genesis of communicability depends on the coexistence of two conditions: a transmitting host lacking in restraining influences, permitting the acquisition of physiological lability by the microorganism; and the development of adaptive mechanisms in the bacterial cell, facilitating survival under atmospheric conditions and subsequent colonization in the environment of human tissues.
One Year Treatment with Salmeterol Compared with Beclomethasone in Children with Asthma
Authors: ANJA A. P. H. VERBERNE, CHRIS FROST, RUURD JAN ROORDA, HAN van der LAAG, KAREL F. KERREBIJN
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

The aim of this study was to compare the effects of salmeterol and beclomethasone on lung function and symptoms in children with mild to moderate asthma. Sixty-seven children not treated with inhaled corticosteroids were randomized in a double-blind parallel study either to salmeterol 50 μ g b.i.d. or beclomethasone 200 μ g b.i.d. After one year, FEV1 significantly increased in the beclomethasone group, whereas in the salmeterol group there was a small reduction. Differences between groups were 14.2% predicted (p < 0.0001) and 7.0% predicted (p = 0.007) for pre- and postbronchodilator FEV1 values, respectively. PD20 methacholine decreased by 0.73 DD (p = 0.05) in the salmeterol group and increased by 2.02 DD (p < 0.0001) in the beclomethasone group. Morning and evening PEF and symptom scores improved in both groups, although more in the beclomethasone group. Asthma exacerbations, for which prednisolone was needed, were more frequent in the salmeterol group (17 versus two), as were the number of withdrawals due to exacerbations (six versus one). However, growth was significantly slower in the beclomethasone group ( − 0.28 SDS) compared with that in the salmeterol group ( − 0.03 SDS) (p = 0.001). We conclude that treatment with a moderate dose of beclomethasone is superior to salmeterol in children with mild to moderate asthma and recommend that salmeterol should not be used as monotherapy.
Pathogenesis and Prevention of Bone Loss in Patients Who Have Kidney Disease and Receive Long-Term Immunosuppression
Authors: John Cunningham
Journal: Journal of the American Society of Nephrology (2006)

The coexistence of kidney disease with a need for immunosuppressive therapy leads to the convergence of several threats to bone. These comprise general effects of the primary disease, <i>e.g.</i>, inflammatory state, more specific effects of acute renal failure or chronic kidney disease, and effects of therapies. Multisystem inflammatory disease that requires immunosuppression is associated frequently with kidney damage, and any reduction of kidney function that takes the patient into or beyond chronic kidney disease stage 2 for more than a short time is likely to have a negative impact on bone health. Bone mineral density frequently is low and fracture rates are high, although correlations often are poor. Chronic inflammation leads to local and systemic imbalance between bone formation and resorption. Upregulation of NF-κβ ligand (RANKL) and variable downregulation of osteoprotegerin are implicated, and bone health may improve in response to treatment of the inflammatory state. Certain immunosuppressive agents, especially glucocorticoids and calcineurin inhibitors, contribute further to bone loss. Antiresorptive agents such as bisphosphonates are used widely and, although able to prevent loss of bone mineral density, have uncertain effects on fracture rates. Augmentation of anabolic activity is desirable but elusive. Synthetic parathyroid hormone is untested but has potential. Manipulation of the RANKL/osteoprotegerin system now is feasible using antibodies to RANKL or synthetic osteoprotegerin. In the future, manipulation of the calcium-sensing receptor using calcimimetic or calcilytic agents may allow the anabolic effects of parathyroid hormone to be harnessed to good effect. With all of these therapies, it will be important to assess response in relation to important clinical end points such as fracture.
Paracrine Regulation of Angiogenesis and Adipocyte Differentiation During In Vivo Adipogenesis
Authors: Dai Fukumura, Akira Ushiyama, Dan G. Duda, Lei Xu, Joshua Tam, V. Krishna, K. Chatterjee, Igor Garkavtsev, Rakesh K. Jain
Journal: Circulation Research (2003)

With an increasing incidence of obesity worldwide, rational strategies are needed to control adipogenesis. Growth of any tissue requires the formation of a functional and mature vasculature. To gain mechanistic insight into the link between active adipogenesis and angiogenesis, we developed a model to visualize noninvasively and in real time both angiogenesis and adipogenesis using intravital microscopy. Implanted murine preadipocytes induced vigorous angiogenesis and formed fat pads in a mouse dorsal skin-fold chamber. The newly formed vessels subsequently remodeled into a mature network consisting of arterioles, capillaries, and venules, whereas the preadipocytes differentiated into adipocytes as confirmed by increased aP2 expression. Inhibition of adipocyte differentiation by transfection of preadipocytes with a peroxisome proliferator-activated receptor γ dominant-negative construct not only abrogated fat tissue formation but also reduced angiogenesis. Surprisingly, inhibition of angiogenesis by vascular endothelial growth factor receptor-2 (VEGFR2) blocking antibody not only reduced angiogenesis and tissue growth but also inhibited preadipocyte differentiation. We found that part of this inhibition stems from the paracrine interaction between endothelial cells and preadipocytes and that VEGF–VEGFR2 signaling in endothelial cells, but not preadipocytes, mediates this process. These findings reveal a reciprocal regulation of adipogenesis and angiogenesis, and suggest that blockade of VEGF signaling can inhibit in vivo adipose tissue formation. The full text of this article is available online at http://www.circresaha.org.
Science, medicine, and the future: Pharmacogenetics
Authors: C R. Wolf
Journal: BMJ (2000)

Individual variation in response to drugs is a substantial clinical problem. Such variation ranges from failure to respond to a drug to adverse drug reactions and drug-drug interactions when several drugs are taken concomitantly. The clinical consequences range from patient discomfort through serious clinical illness to the occasional fatality. One UK study has suggested that about 1 in 15 hospital admissions are due to adverse drug reactions,1 and a recent US study estimated that 106 000 patients die and 2.2 million are injured each year by adverse reactions to prescribed drugs.2
Colchicine treatment of cirrhosis: Questions
Authors: Norman D. Grace
Journal: Hepatology (1989)

There is preliminary evidence that colchicine, an inhibitor of collagen synthesis, may be beneficial in the treatment of cirrhosis of the liver. To evaluate the use of colchicine (1 mg per day, five days per week) in the treatment of hepatic cirrhosis, we performed a randomized, double-blind, placebo-controlled trial in which 100 patients were followed for up to 14 years. Forty-five patients had alcoholic cirrhosis, 41 had posthepatitic cirrhosis, and the remaining 14 had cirrhosis with various other causes. Histologic studies were available for 92 percent of patients. Seventy-three patients were in Child-Turcotte class A, 26 were in class B, and one was in class C. Fifty-four patients received colchicine, and 46 received placebo. The overall survival in the colchicine group was markedly better than in the placebo group (median survival, 11 and 3.5 years, respectively; P < 0.001). The cumulative 5-year survival rates were 75 percent in the colchicine group and 34 percent in the placebo group; the corresponding 10-year survival rates were 56 percent and 20 percent. Among the 30 patients treated with colchicine who underwent repeated liver biopsies, histologic improvement was seen in 9; the liver appeared normal in 2, and 7 had minimal portal fibrosis. No histologic improvement was observed in the 14 members of the placebo group who had two or more biopsies. Few side effects were observed in either group.
The Tumor Suppressor UCHL1 Forms a Complex with p53/MDM2/ARF to Promote p53 Signaling and Is Frequently Silenced in Nasopharyngeal Carcinoma
Authors: Lili Li, Qian Tao, Hongchuan Jin, Andrew van Hasselt, Fan Fong Poon, Xian Wang, Mu-Sheng Zeng, Wei-Hua Jia, Yi-Xin Zeng, Anthony T.C. Chan, Ya Cao
Journal: Clinical Cancer Research (2010)

Nasopharyngeal carcinoma is prevalent in southern China and Southeast Asia, with distinct geographic and ethnic distribution. One candidate susceptibility locus has been identified at 4p11-14, with the associated candidate gene(s) not identified yet. This study investigated the role of ubiquitin carboxyl-terminal hydrolase L1 (UCHL1) in nasopharyngeal carcinoma pathogenesis.UCHL1 expression and methylation were examined in nasopharyngeal carcinoma. Furthermore, the mechanism of its tumor-suppressive function was elucidated in nasopharyngeal carcinoma cells.Through genomewide expression profiling, we identified UCHL1, a 4p14 gene normally expressed in normal upper respiratory tract tissues, being silenced in all nasopharyngeal carcinoma cell lines. Its silencing is mediated by CpG methylation because UCHL1 promoter methylation was detected in all silenced cell lines, and pharmacologic demethylation reactivated UCHL1 expression along with concomitant promoter demethylation. UCHL1 methylation was also frequently detected in primary tumors but only weakly detected in few normal nasopharyngeal tissues, indicating that the methylation-mediated silencing of UCHL1 is important in nasopharyngeal carcinoma pathogenesis. Ectopic UCHL1 expression dramatically inhibited the growth of nasopharyngeal carcinoma cells through promoting tumor cell apoptosis. We further found that UCHL1 formed a complex with p53/p14(ARF)/Mdm2 p53 binding protein homolog (mouse), MDM2 and activated the p53 signaling pathway. UCHL1 expression extended p53 and p14(ARF) protein half-life and shortened MDM2 protein half-life.These results indicate that UCHL1 could deubiquitinate p53 and p14(ARF) and ubiquitinate MDM2 for p53 stabilization to promote p53 signaling, thus involved in nasopharyngeal carcinoma pathogenesis, whereas it is frequently silenced in this tumor.
C4d-Positive Acute Humoral Renal Allograft Rejection
Authors: GEORG A. BÖHMIG, HEINZ REGELE, MARKUS EXNER, VICTOR DERHARTUNIAN, JOSEF KLETZMAYR, MARCUS D. SÄEMANN, WALTER H. HÖRL, WILFRED DRUML, BRUNO WATSCHINGER
Journal: Journal of the American Society of Nephrology (2001)

There is increasing evidence for an important pathogenetic role of alloantibodies in acute renal allograft rejection. Acute humoral rejection (AHR) has been reported to be associated with a poor transplant survival. Although treatment modalities for cellular rejection are fairly well established, the optimal treatment for AHR remains undefined. Ten of 352 kidney allograft recipients transplanted at the authors' institution between November 1998 and September 2000 were diagnosed as having AHR, supported by severe graft dysfunction, C4d deposits in peritubular capillaries (PTC), and accumulation of granulocytes in PTC. AHR was diagnosed 18.9 ± 17.5 d posttransplantation. All patients were subjected to immunoadsorption (IA) with protein A (median number of treatment sessions, 9; range, 3 to 17). Seven recipients with additional signs of cellular rejection (according to the Banff classification) received also antithymocyte globulin. In nine of ten patients, AHR was associated with an increase in panel reactive antibody reactivity. A pathogenetic role of alloantibodies was further supported by a positive posttransplant cytotoxic crossmatch in all tested recipients (n = 4). In nine of ten recipients, renal function recovered after initiation of anti-humoral therapy. One patient lost his graft shortly after initiation of specific therapy. Another recipient with partial reversal of AHR returned to dialysis 8 mo after transplantation. Mean serum creatinine in functioning grafts was 2.2 ± 1.2 mg/dl after the last IA session (n = 9) and 1.5 ± 0.5 mg/dl after a follow-up of 14.2 ± 7.1 mo (n = 8). In conclusion, this study suggests that AHR, characterized by severe graft dysfunction, C4d staining, and peritubular granulocytes, can be effectively treated by timely IA. In the majority of patients, IA treatment can restore excellent graft function over a prolonged time period.
RNA synthesis and RNA content of nuclei prepared from hearts during hypertrophy
Authors: K. J. KAKO, K. VARNAI, M. BEZNAK
Journal: Cardiovascular Research (1972)

Rat heart nuclei were isolated and contents of DNA, RNA and protein, and activity of DNA-dependent RNA polymerase were determined during development of cardiac hypertrophy. Both protein/DNA and RNA/DNA ratios of isolated nuclei were increased within 24 hr after aortic constriction and remained high for a two weeks' observation period, suggesting an increased RNA synthesis and enlargement of nuclei. The apparent activity of polymerase of the control hearts measured in the presence of Mn2+ and (NH4)2 SO4 was 2·5-fold higher than that measured in the presence of Mg2+ . The activity in the sham-operated rats was elevated in the first three days. The increase in RNA polymerase activity after aortic banding was biphasic in that an early, transient increase was observed at 4 hr after the operation and a later and greater increase appeared at approximately 24 hr and remained at a high level for several days. The early increase in the Mg2+ activated system was 109% and the Mn2+ system 169%, whereas at the peak that appeared on the third-fourth day the respective increases were 618% and 310%. The results suggest a predominant synthesis of messenger RNA at the early stage of hypertrophy followed later by an increased synthesis of ribosomal RNA.
Outcome Predictors for the Increasing PSA State After Definitive External-Beam Radiotherapy for Prostate Cancer
Authors: Michael J. Zelefsky, Leah Ben-Porat, Howard I. Scher, Heather M. Chan, Paul A. Fearn, Zvi Y. Fuks, Steven A. Leibel, E.S. Venkatraman
Journal: Journal of Clinical Oncology (2005)

To identify predictors of distant metastases (DM) among patients who develop an isolated prostate-specific antigen (PSA) relapse after definitive external-beam radiotherapy for clinically localized prostate cancer.A total of 1,650 patients with clinical stage T1 to T3 prostate cancer were treated with high-dose three-dimensional conformal radiotherapy. Of these, 381 patients subsequently developed three consecutive increasing PSA values and were characterized as having a biochemical relapse. The median follow-up time was 92 months from the completion of radiotherapy.The 5-year incidence of DM after an established PSA relapse was 29%. In a multivariate analysis, PSA doubling time (PSA-DT; P < .001), the clinical T stage (P < .001), and Gleason score (P = .007) were independent variables predicting for DM after established biochemical failure. The PSA-DT for favorable-, intermediate-, and unfavorable-risk patients who developed a biochemical failure was 20.0, 13.2, and 8.2 months, respectively (P < .001). The 3-year incidence of DM for patients with PSA-DT of 0 to 3, 3 to 6, 6 to 12, and more than 12 months was 49%, 41%, 20%, and 7%, respectively (P < .001). Patients with PSA-DT of 0 to 3 and 3 to 6 months demonstrated a 7.0 and 6.6 increased hazard of developing DM or death, respectively, compared with patients with a DT more than 12 months.In addition to clinical stage and Gleason score, PSA-DT was a powerful predictor of DM among patients who develop an isolated PSA relapse after external-beam radiotherapy for prostate cancer. Patients who develop biochemical relapse with PSA-DT < or = 6 months should be considered for systemic therapy or experimental protocols because of the high propensity for rapid DM development.
PYROGLYPHID MITES, XEROPHILIC FUNGI AND ALLERGENIC ACTIVITY IN DUST FROM HOSPITAL MATTRESSES
Authors: B. v. d. LUSTGRAAF, W. JORDE
Journal: Allergy (1977)

Dust from mattresses of different composition and age was analysed for mites, xerophilic fungi and allergenic activity. The mites of the genus Demodex were the most abundant (58.2 per cent). Also pyroglyphid mites occurred commonly (36.6 per cent). Pyroglyphid mites were present in small numbers (mean: 1 specimen/0.2 g of dust) in 12 out of the 17 older polyester-foam mattresses. The 11 cotton-horsechair mattresses and the newly used polyester-foam mattresses (three tested) were without them. The dust from the cotton-horsehair mattresses had a significantly higher allergenic activity than from those of polyester-foam. Xerophilic fungi were isolated in three out of 31 mattresses. The species isolated belonged to the genus Aspergillus and Eurotium. E. repens occurred most frequently. Disinfection of mattresses was suggested to have a negative influence on the occurrence of mites and fungi.
Spontaneous bacterial peritonitis prophylaxis in the era of healthcare associated infection
Authors: Hasnain M Jafferbhoy, Michael H Miller, W Gashau, C ChandraShekar, Elaine B Henry, Michael Lockhart, John F Dillon
Journal: Gut (2012)

We read with interest the review article by Wiest et al 1 and applaud them for an excellent review highlighting spontaneous bacterial peritonitis SBP as a serious complication of cirrhosis. In particular, the emphasis on timely diagnosis of SBP and the use of appropriate antibiotics for treatment and prophylaxis is vital as emergence of resistant organism becomes a greater challenge. The section on prophylaxis draws the important distinction between community acquired and nosocomial SBP. In hepatology units, nosocomial infection is much more common than community acquired SBP, leading to many units having a policy of antibiotic prophylaxsis for high risk hospital inpatients only for the duration of admission,2 3 most commonly using norfloxacin. More recently, this has been recognised as a risk factor for healthcare associated infections. Due to a change in hospital antimicrobials policy we evaluated two consecutive cohorts …
Gastric ulcers, blood groups, and acid secretion
Authors: H. D. Johnson, A. H. G. Love, N. C. Rogers, A. P. Wyatt
Journal: Gut (1964)

EDITORIAL SYNOPSIS This study suggests that there are two groups of gastric ulcers, one associated with very marked blood group 0 predominance and the other with hyposecretion and no evidence of group 0 predominance and with some evidence for an excess of group A.