158 research outputs found
NPC1L1 inhibitor ezetimibe is a reliable therapeutic agent for non-obese patients with nonalcoholic fatty liver disease
<p>Abstract</p> <p>Background</p> <p>We recently examined the distribution of abdominal fat, dietary intake and biochemical data in patients with nonalcoholic fatty liver disease (NAFLD) and found that non-obese NAFLD patients did not necessarily exhibit insulin resistance and/or dysregulated secretion of adipocytokines. However, dietary cholesterol intake was superabundant in non-obese patients compared with obese patients, although total energy and carbohydrate intake was not excessive. Therefore, excess cholesterol intake appears to be one of the main factors associated with NAFLD development and liver injury.</p> <p>Methods</p> <p>We reviewed a year of follow-up data of non-obese NAFLD patients treated with Niemann-Pick C1 like 1 inhibitor ezetimibe to evaluate its therapeutic effect on clinical parameters related to NAFLD. Without any dietary or exercise modification, 10 mg/day of ezetimibe was given to 8 patients. In 4 of 8 patients, ezetimibe was administered initially. In the remaining 4 patients, medication was switched from ursodeoxycholic acid to ezetimibe.</p> <p>Results</p> <p>In each patient, body mass index was maintained under 25 kg/m<sup>2 </sup>during the observation period. Serum ALT levels significantly decreased within 6 months and in 4 patients levels reached the normal range (<30 U/L), which was accompanied with at least a 10% decrease in serum total cholesterol and LDL-cholesterol. However, ultrasonographic findings of fatty liver did not show obvious improvement for a year.</p> <p>Conclusion</p> <p>We conclude that the cholesterol absorption inhibitor ezetimibe can suppress hepatic injury in non-obese patients with NAFLD and that ezetimibe may offer a novel treatment for NAFLD.</p
A Strong Correlation between Serum soluble IL-2 Receptor (sIL-2R) and Atypical Lymphocytosis
Activated lymphocytes morphologically change into large aberrant cells known as atypical lymphocytes (atyLy). AtyLy are seen in various non-neoplastic conditions such as viral infection of Epstein-Barr virus, cytomegalovirus and hepatitis viruses. These activated cells release various cytokines or soluble receptors such as soluble interleukin-2 receptor (sIL-2R) and Fas-receptor (Fas-R). Accordingly, we measured serum sIL-2R in 25 pediatric patients. The data and other hematological/biochemical parameters were analyzed by the statistical processing method of Principle Component Analysis (PCA). 23 out of 25 patients with atypical lymphocytosis-related conditions (atyLy/lymphocyte ratio >5%) were found to have higher serum sIL-2R levels than the cut-off-value of 400 U/mL. The correlation between sIL-2R and the atyLy/lymphocyte ratio was the best indicator for discriminating the severity of disease. The first component (contribution ratio: 0.384) of PCA showed that lymphocyte activity was mostly represented by sIL-2R, lactate dehydrogenase, white blood cell count, lymphocyte count, lymphocyte percentile and atyLy/lymphocyte ratio. Conclusively, these findings suggest a strong correlation between serum sIL-2R level and atypical lymphocytosis
The Uteroglobin Gene G38A Polymorphism Is Not Associated with Kawasaki Disease
This study analyzed the genomic DNA extracted from 170 patients with Kawasaki disease as well as their clinical and laboratory parametersto determine whether uteroglobin gene polymorphism, which may be associated with the morbidity rate and severity of IgA nephropathy, is involvedin the pathogenesis of Kawasaki disease, which is another type of vasculitic syndrome in childhood. The uteroglobin genotype at position38 was determined by Sau96I digestion of PCR products. The uteroglobin genotype and allele frequency in Kawasaki disease patientswere compared with those of published control data reported by three independent studies on Japanese individuals. The clinical parametersinvestigated were age at onset, gender, duration of fever, white blood cell count, C-reactive protein, aspartate aminotransferase, alanineaminotransferase and total protein. No significant difference associated with the uteroglobin genotype was observed in the clinical parameters.The genotypic and allele frequencies at position 38 of the uteroglobin gene did not differ significantly in the three studies of Japanese healthycontrols and the present study. The logistic regression analysis demonstrated that no clinical parameter was associated with the progressionto coronary artery lesions except for the duration of fever (odds ratio = 1.7; 95% confidential interval = 1.42-2.05). In conclusion, the presentstudy failed to prove an association of uteroglobin gene polymorphism with the morbidity rate or the severity of Kawasaki disease, but suggestedthe existence of a factor contributing to the onset of Kawasaki disease and progression to coronary artery lesions in Kawasaki diseasepatients
Les normes, comment?
La description normalisée des ressources d’enseignement et d’apprentissage requiert l’utilisation d’outils d’implantation conformes aux conventions d’un standard ou d’une norme internationale et un réseau d’entraide et d’accompagnement
Quantitative Features of serum sIL-2R level in Patients with Mature B-Cell Lymphoma? Involvement of LDH
Serum Lactate Dehydrogenase (LDH) activity and soluble IL-2 Receptor-alpha (sIL-2R) levels are monitored as a marker ofdisease activity in patients with lymphoma. Although adult T-cell leukemia (ATL) cells are well known to release large amounts ofsIL-2R,it remains unclear to what extent B-cell lymphoma cells shed sIL-2R in sera. Subtypes of mature B-cell lymphoma, includingCD25+ hairy leukemic cells, were examined for the characteristics of sIL-2R levels in each subtype. In normal controls, theserum sIL-2R mean value was 260u/mL.The median serum sIL-2R value for 64 B-cell lymphoma cases was 506 u/mL;by subtypethe median values were as follows: 1157 u/mL for 7 cases of chronic lymphocytic leukemia/hairy cell leukemia (CLL/HCL), 451u/mL for 38 cases of diffuse large B-cell lymphoma (DLBCL), and 456 u/mL for 19 cases of follicular Lymphoma (FL). The medianvalues of serum LDH activity by the above subtypes were 175 IU/mL, 204 IU/mL, and 198 IU/mL, respectively. There wasdistinct inter-subtype and inter-patient variation of serum sIL-2R.In particular, inter-case variation could be grouped into value forthree concentration ranges: less than 300 u/mL, 300-1000 u/mL, and greater than 1000 u/mL. Cases with serum sIL-2R valuesof 1000 u/mL or more tended to have an especially high sIL-2R to LDH ratio, suggesting a close relationship between high sIL-2Rand CD25-expressing lymphoma cells. With respect to sIL-2R and LDH levels, CLL/HCL, DLBCL, and FL showed similar distributions.Moreover, for sIL-2R levels exceeding 1000u/mL, sIL-2R levels were randomly high according to the LDH status. Conclusively,the combination of serum sIL-2R level and LDH activity can provide a better understanding of characteristics of subtypesof mature B-Cell Lymphoma and can be used as a reliable surrogate marker for evaluating numerical and biological data
De Novo Mutations in GNAO1, Encoding a Gαo Subunit of Heterotrimeric G Proteins, Cause Epileptic Encephalopathy
Heterotrimeric G proteins, composed of α, β, and γ subunits, can transduce a variety of signals from seven-transmembrane-type receptors to intracellular effectors. By whole-exome sequencing and subsequent mutation screening, we identified de novo heterozygous mutations in GNAO1, which encodes a Gαo subunit of heterotrimeric G proteins, in four individuals with epileptic encephalopathy. Two of the affected individuals also showed involuntary movements. Somatic mosaicism (approximately 35% to 50% of cells, distributed across multiple cell types, harbored the mutation) was shown in one individual. By mapping the mutation onto three-dimensional models of the Gα subunit in three different complexed states, we found that the three mutants (c.521A>G [p.Asp174Gly], c.836T>A [p.Ile279Asn], and c.572_592del [p.Thr191_Phe197del]) are predicted to destabilize the Gα subunit fold. A fourth mutant (c.607G>A), in which the Gly203 residue located within the highly conserved switch II region is substituted to Arg, is predicted to impair GTP binding and/or activation of downstream effectors, although the p.Gly203Arg substitution might not interfere with Gα binding to G-protein-coupled receptors. Transient-expression experiments suggested that localization to the plasma membrane was variably impaired in the three putatively destabilized mutants. Electrophysiological analysis showed that Gαo-mediated inhibition of calcium currents by norepinephrine tended to be lower in three of the four Gαo mutants. These data suggest that aberrant Gαo signaling can cause multiple neurodevelopmental phenotypes, including epileptic encephalopathy and involuntary movements
Lansoprazole for secondary prevention of gastric or duodenal ulcers associated with long-term low-dose aspirin therapy: results of a prospective, multicenter, double-blind, randomized, double-dummy, active-controlled trial
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