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991.
Francesca Fernandez Teresa Esposito Rod A Lea Natalie J Colson Alfredo Ciccodicola Fernando Gianfrancesco Lyn R Griffiths 《BMC medical genetics》2008,9(1):109
Background
Migraine is a neurological disorder characterized by recurrent attacks of severe headache, affecting around 12% of Caucasian populations. It is well known that migraine has a strong genetic component, although the number and type of genes involved is still unclear. Prior linkage studies have reported mapping of a migraine gene to chromosome Xq 24–28, a region containing a cluster of genes for GABA A receptors (GABRE, GABRA3, GABRQ), which are potential candidate genes for migraine. The GABA neurotransmitter has been implicated in migraine pathophysiology previously; however its exact role has not yet been established, although GABA receptors agonists have been the target of therapeutic developments. The aim of the present research is to investigate the role of the potential candidate genes reported on chromosome Xq 24–28 region in migraine susceptibility. In this study, we have focused on the subunit GABA A receptors type ε (GABRE) and type θ (GABRQ) genes and their involvement in migraine. 相似文献992.
Samuele Peppolonii Ronald B. Herberman Elieser Gorelik 《Clinical & experimental metastasis》1987,5(1):43-56
The metastatic ability of 3LL tumor following in vitro irradiation with ultraviolet (u.v.) light was studied. Tumor cells were exposed to two courses of u.v.-irradiation (3LL × 2u.v. cells) and after two weeks of culture they were inoculated intravenously (i.v.) into syngeneic mice. These cells produced significantly fewer pulmonary metastases than the untreated population. In addition, intrafootpad (i.f.p.) injections of 3LL × 2u.v. cells into immunocompetent animals induced tumors only in 40 per cent of recipients. Interestingly, in normal mice with progressively growing 3LL × 2u.v. tumors, the formation of spontaneous pulmonary metastases was prevented, whereas metastatic foci were observed in 70 per cent of the nude recipients. The metastatic properties of u.v.-treated tumor cells were further analysed by using individual clones with varying immunogenicity. We found that variants with augmented immunogenicity also showed a parallel decrease in metastatic potential. Studies on H-2 antigen expression in different clones revealed that immunogenic and low metastatic variants expressed levels of H-2 antigens higher than the tumorigenic and metastatic clones. Finally, by using cyclophosphamide (Cy) treatment and adoptive transfer of immune spleen cells we were able to eradicate macroscopic 3LL pulmonary metastasis. These results demonstrate that the decrease of metastatic ability in u.v.-treated cells was mainly due to an increase in their immunogenicity and H-2 antigen expression. 相似文献
993.
Andrew A White Donald D Stevenson Ronald A Simon 《Annals of allergy, asthma & immunology》2005,95(4):330-335
BACKGROUND: The blocking effect of controller medications for asthma could have an effect on the outcome of aspirin challenges in patients suspected of having aspirin-exacerbated respiratory disease (AERD). OBJECTIVE: To evaluate whether there was any blocking effect of long-acting beta2-agonists, systemic corticosteroids, and/or inhaled corticosteroids alone or as co-therapy with leukotriene modifier drugs (LTMDs). METHODS: Between 1981 and 2004, 678 patients with suspected AERD were admitted for aspirin challenge and desensitization. All patients had asthma, chronic sinusitis, nasal polyposis, and at least 1 historical reaction to a nonsteroidal anti-inflammatory drug. Asthma controller medications taken during aspirin challenge were recorded and analyzed with respect to their potential effects on 4 possible outcomes of aspirin challenge, namely, naso-ocular reaction, lower airway reaction, classic upper and lower airway reaction, or a negative challenge result. RESULTS: When compared with AERD patients who received no controller medications, the combined use of LTMDs, inhaled corticosteroids, and long-acting beta2-agonists led to a statistically significant change in aspirin challenge outcomes (P = .009), mainly shifting the reaction from a classic upper and lower respiratory tract reaction to naso-ocular reactions only. LTMDs appeared to have the strongest effect (P < .001) in blocking lower respiratory tract reactions. Systemic corticosteroids did not have the same effects. Blocking of both upper and lower respiratory tract reactions to aspirin as a result of taking controller medications did not occur. CONCLUSION: Controller medications are frequently needed to stabilize airways of patients with AERD. LTMDs alone or in combination with other controllers blocked lower respiratory tract reactions during aspirin challenge in some patients with AERD but did not change the overall rate of positive aspirin challenge results and did not lead to false-negative challenges. 相似文献
994.
James F Jones Elizabeth M Maloney Roumiana S Boneva Ann-Britt Jones William C Reeves 《BMC complementary and alternative medicine》2007,7(1):12
Background
Chronic fatiguing illnesses, including chronic fatigue syndrome (CFS), pose a diagnostic and therapeutic challenge. Previous clinical reports addressed the utilization of health care provided to patients with CFS by a variety of practitioners with other than allopathic training, but did not examine the spectrum of complementary and alternative medicine (CAM) therapies used. This study was designed to measure CAM therapy use by persons with fatiguing illnesses in the United States population. 相似文献995.
Ronald N. Maclean William K. Prater Carmen B. Lozzio John M. Opitz 《American journal of medical genetics. Part A》1983,14(2):373-380
We report on an infant with broad and severely angulated short femora as the most salient manifestation of a generalized skeletal dysplasia. Other findings include congenital bowing of other long bones, narrow thorax, platyspondyly, micrognathia, and skin dimples. A marked improvement of the bowing and of the irregular flare of the metaphyses was noted over a period of 6 mo. Congenital bowing of long bones can be an isolated finding or associated with other anomalies, so the purpose of reporting all cases is important for further nosologic and pathogenetic elucidation. Because of the severity of the femoral involvement, the condition has been called kyphomelic dysplasia. It may be an autosomal recessive trait. recessive trait. 相似文献
996.
997.
Rearrangement of Valproate Glucuronide in a Patient with Drug-Associated Hepatobiliary and Renal Dysfunction 总被引:1,自引:1,他引:0
Ronald G. Dickinson Ruth M. Kluck Wayne D. Hooper Marc Patterson John B. Chalk Mervyn J. Eadie 《Epilepsia》1985,26(6):589-593
Formation of beta-glucuronidase-resistant "glucuronides" of valproic acid (VPA) by intramolecular rearrangement of biosynthetic valproate glucuronide in vivo was investigated in a patient diagnosed with VPA-associated hepatobiliary and renal dysfunction. Plasma elimination half-life of VPA following cessation of the drug was 13.9 h. At the time of the toxicity, the concentration of conjugated VPA in plasma was very high (36-54% of nonconjugated VPA levels) relative to that in normal patients (2.9%). The fraction of conjugated VPA resistant to beta-glucuronidase hydrolysis was 0.28-0.47 in plasma and 0.15-0.42 in urine. The corresponding fraction in urine from normal patients receiving VPA therapy was 0.044. The evidence was consistent with retarded elimination of biosynthetic VPA glucuronide caused by renal and hepatobiliary dysfunction. Consequent prolongation of circulation of VPA glucuronide at the slightly alkaline pH of blood would permit extensive intramolecular rearrangement which is known to be pH-, temperature-, and time-dependent. The biological consequences of the presence of such beta-glucuronidase-resistant conjugated VPA in vivo are largely unknown. 相似文献
998.
Peter Bright-Asare Stephen J. Sontag Ronald J. Gould Douglas L. Brand Walter M Roufail 《Digestive diseases and sciences》1986,31(2):63S-67S
This study was undertaken to evaluate the efficacy of misoprostol taken twice daily for the healing of duodenal ulcer. Three hundred thirty patients with endoscopically proven duodenal ulcer participated in a multicenter, double-blind, controlled trial comparing placebo with misoprostol 200 μg and 400 μg twice daily for up to four weeks. Patient characteristics were similar in all three treatment groups. Ulcers were between 0.3 cm and 2.0 cm in length. Healing was determined by endoscopy at two weeks; if ulcers were not healed, endoscopy was repeated at four weeks. All patients were given Al(OH)3 antacid (up to 54 meq a day) to be used as needed for pain. Healing rates at four weeks for a total of 280 evaluable patients in the three treatment groups were as follows: misoprostol 400 μg bid, 65.4%; misoprostol 200 μg bid, 52.9%; and placebo, 42.2%. Misoprostol 400 μg bid was superior to placebo (P=0.002) in healing ulcers. However, the healing rate for misoprostol 200 μg bid did not differ significantly from placebo. The percentage of nonsmokers who healed at four weeks was higher than that of smokers in both misoprostoltreatment groups, although the difference was not analyzed for statistical significance. There were no differences in antacid consumption or pain relief among the three experimental groups during the study. Diarrhea was the most common side effect but was mild and self-limiting, occurring in 8.9%, 5.9%, and 1.8% of the misoprostol 400 μg, 200 μg, and placebo groups, respectively. These results indicate that misoprostol 400 μg, 200 μg, and for four weeks is effective and safe for the treatment of duodenal ulcers. 相似文献
999.
Chiao-Hsi Chiang Ronald D. Schoenwald 《Journal of pharmacokinetics and pharmacodynamics》1986,14(2):175-211
A single topical instillation of clonidine-3H HCl solution (0.2%) was administered to the rabbit eye (30 μl) in order to study the drug's ocular pharmacokinetics. Seven different tissues and plasma were excised and assayed for drug over 180min. By 45–60 min pseudoequilibrium is reached for the cornea, iris/ciliary body, and aqueous humor. Thereafter, drug levels in these tissues decline in parallel. The data are fit separately to a physiological model and a classical diffusion model for which seven ocular tissue compartments and a plasma reservoir are constructed for each model. Clearance terms and distribution equilibrium coefficients are determined from the tissue level data and used as parameters in fitting the mass balance differential equations representing the physiological model. The model parameters can also be fit to a 0.4% single dose. In a separate experiment, a topical infusion technique was designed to provide a constant rate input to the cornea until an apparent steady state was reached in aqueous humor at 55 min. Aqueous humor levels were assayed for clonidine over the infusion and postinfusion periods. The physiological model parameters are fit to the topical infusion data and show good agreement between the predicted and experimental data. The classical model is too complex to fit the data to integrated exponential equations primarily because the method of residuals is inadequate in determining a sufficient set of initial estimates. This is overcome by dividing the eight-compartment model into seven fragmental models, each representing one to five compartments. A stepwise procedure is developed in which initial estimates are obtained for each separate fragmental model and refined. The refined parameter values can then be used as initial estimates for the complex model. Differential equations for the complex model are fit simultaneously to tissue levels representing each compartment. By observation, the classical model fit the data more closely than the physiological model. Statistical moment theory is also applied to the topical infusion data to determine ocular pharmacokinetic parameters for clonidine. The calculated values are: corneal absorption rate constantk a , 0.00139 min?1; aqueous humor elimination rate constantk 10 , 0.0658min?1; mean residence timeMRT d , 35.6 min; apparent steadystate volume of distributionV ss, 0.530 ml; and ocular clearanceQ e , 14.9 =μl/min. The fraction absorbed from the single instillation is estimated as 0.0163. 相似文献
1000.
Ronald A. Chung Carol S. Williams 《Archives of environmental contamination and toxicology》1986,15(5):581-588
In L-2071 tissue culture cells, 50 ppm (50 g/ml culture medium) each of dieldrin or DDT reduced total cell count and the rate of14C-leucine incorporation into protein and14C-uridine incorporation into total RNAs; this was the result of an increased rate of14C-uridine incorporation into cytoplasmic soluble and 4S RNA cellular fraction. Total amino acid acceptor activity decreased with dieldrin and DDT treatments, which suggests an actual decrease in functional tRNAs. Dieldrin reduced glutamyl- and aspartyl-tRNA activities whereas phenylalanyl-, tyrosyl-, threonyl-, leucyl-, isoleucyl-, seryl-, and prolyl-tRNA activities decreased with both pesticides. Valyl-, lysyl-, glycyl-, alanyl-, histidyl-, and arginyl-tRNA activities were only slightly changed. The effect of dieldrin was generally greater than that of DDT. In addition, there was degradation of 28S and 18S RNAs to fragments isolated with 4S RNAs. Cells treated with 0.5 and 10 ppm levels of dieldrin demonstrated decreased14C-uridine incorporation into 28S RNAs and increased incorporation into 18S and 4S RNAs after 3 hours and 3 to 6 hours, respectively. Incorporation levels returned to near control levels, thereafter, in whole cell preparations, but remained different from controls when nuclear and cytoplasmic fractions were assessed individually. 相似文献