Phenotype and genotype correlation of the microconversion from the CYP21A1P to the CYP21A2 gene in congenital adrenal hyperplasia

Deficiency of 21-hydroxylase is the most common form of congenital adrenal hyperplasia (CAH-21OH). We determined by allele-specific PCR the frequency of microconversion in the CYP21A2 gene in 50 Brazilian patients with the classical (salt wasting: SW and simple virilizing: SV) forms and nonclassical (NC) form of CAH-21OH and correlated genotype with phenotype. Genotypes were classified into three mutation groups (A, B, and C) based on the amount of enzymatic activity in in vitro studies using adrenal cells. In 94 unrelated alleles, we diagnosed 76% of the affected alleles after screening for 7 microconversions. The most frequent point mutations observed in this series were I172N (19%), V281L (18%), and IVS2,A/C>G,-12 (15%). In the SW form, the most frequent mutation was IVS2,A/C>G,-12 (38%), in the SV form it was I172N (53%), and in the NC form it was V281L (57.7%). We observed a good correlation between genotype and phenotype. Discordance between genotype and phenotype was found in one SV patient with a mild mutation in one of the alleles (R356W/V281L). However, we cannot rule out the presence of an additional mutation in these alleles. We also observed a good correlation of genotype with 17alpha-hydroxyprogesterone, testosterone, and androstenedione levels. The severity of external genitalia virilization correlated with the severity of mutation. In conclusion, the frequencies described in the present study did not differ from worldwide studies, including the Brazilian population. The few differences observed may reflect individual sample variations. This new Brazilian cohort study suggests the presence of new mutations in Brazilian patients with different forms of CAH-21OH.1311131

Relationship between work rate and oxygen uptake in mitochondrial myopathy during ramp-incremental exercise

We determined the response characteristics and functional correlates of the dynamic relationship between the rate (Δ) of oxygen consumption ( O2) and the applied power output (work rate = WR) during ramp-incremental exercise in patients with mitochondrial myopathy (MM). Fourteen patients (7 males, age 35.4 ± 10.8 years) with biopsy-proven MM and 10 sedentary controls (6 males, age 29.0 ± 7.8 years) took a ramp-incremental cycle ergometer test for the determination of the O2 on-exercise mean response time (MRT) and the gas exchange threshold (GET). The ΔO2/ΔWR slope was calculated up to GET (S1), above GET (S2) and over the entire linear portion of the response (S T). Knee muscle endurance was measured by isokinetic dynamometry. As expected, peak O2 and muscle performance were lower in patients than controls (P O2/ΔWR than controls, especially the S2 component (6.8 ± 1.5 vs 10.3 ± 0.6 mL·min-1·W-1, respectively; P O2/ΔWR (S T) and muscle endurance, MRT-O2, GET and peak O2 in MM patients (P O2/ΔWR below 8 mL·min-1·W-1 had severely reduced peak O2 values (O2) had lower ΔO2/ΔWR (P O2/ΔWR) is typically reduced in patients with MM, being related to increased functional impairment and higher cardiopulmonary stress

Метод трехмерной триангуляции в задачах кластерного анализа

Представлен метод многомерного шкалирования на основе трехмерной триангуляции. Рассмотрена возможность качественного сохранения геометрической структуры множества объектов при отображении многомерного пространства в трехмерное. Приведены результаты применения метода для решения задачи кластеризации на примере периодической системы элементов Д.И. Менделеева. Экспериментально показано, что по критериям качества кластеризации предложенный метод более эффективен в сравнении с методами k-средних и нейронной сети Кохонена.Представлено метод багатовимірного шкалювання на основі тривимірної тріангуляції. Розглянуто можливість якісного збереження геометричної структури множини об’єктів при відображенні багатовимірного простору в тривимірне. Наведено результати застосування методу для вирішення задачі кластеризації на прикладі періодичної системи елементів Д.І. Менделєєва. Експериментально показано, що за критеріями якості кластеризації запропонований метод більш ефективний у порівнянні з методами k-середніх та нейронної мережі Кохонена.The method of multidimensional scaling on the basis of the 3-D triangulation is presented. The qualitative preservation possibility of geometrical structure of objects by multidimensional space mapping to three- dimensional space is considered. The results of application of the method for clustering problem of the Mendeleyev periodic table are presented. It is experimentally shown, that the presented method is more effective by criteria of clustering quality in comparison with the methods of k-averages and the Kohonen neural network

Does hepatocellular carcinoma in non-alcoholic steatohepatitis exist in cirrhotic and non-cirrhotic patients?

Non-alcoholic steatohepatitis (NASH) has been associated with hepatocellular carcinoma (HCC) often arising in histologically advanced disease when steatohepatitis is not active (cryptogenic cirrhosis). Our objective was to characterize patients with HCC and active, histologically defined steatohepatitis. Among 394 patients with HCC detected by ultrasound imaging over 8 years and staged by the Barcelona Clinic Liver Cancer (BCLC) criteria, we identified 7 cases (1.7%) with HCC occurring in the setting of active biopsy-proven NASH. All were negative for other liver diseases such as hepatitis C, hepatitis B, autoimmune hepatitis, Wilson disease, and hemochromatosis. The patients (4 males and 3 females, age 63 ± 13 years) were either overweight (4) or obese (3); 57% were diabetic and 28.5% had dyslipidemia. Cirrhosis was present in 6 of 7 patients, but 1 patient had well-differentiated HCC in the setting of NASH without cirrhosis (fibrosis stage 1) based on repeated liver biopsies, the absence of portal hypertension by clinical and radiographic evaluations and by direct surgical inspection. Among the cirrhotic patients, 71.4% were clinically staged as Child A and 14.2% as Child B. Tumor size ranged from 1.0 to 5.2 cm and 5 of 7 patients were classified as early stage; 46% of all nodules were hyper-echoic and 57% were <3 cm. HCC was well differentiated in 1/6 and moderately differentiated in 5/6. Alpha-fetoprotein was <100 ng/mL in all patients. HCC in patients with active steatohepatitis is often multifocal, may precede clinically advanced disease and occurs without diagnostic levels of alpha-fetoprotein. Importantly, HCC may occur in NASH in the absence of cirrhosis. More aggressive screening of NASH patients may be warranted

Quantum Chaos in Open versus Closed Quantum Dots: Signatures of Interacting Particles

This paper reviews recent studies of mesoscopic fluctuations in transport through ballistic quantum dots, emphasizing differences between conduction through open dots and tunneling through nearly isolated dots. Both the open dots and the tunnel-contacted dots show random, repeatable conductance fluctuations with universal statistical proper-ties that are accurately characterized by a variety of theoretical models including random matrix theory, semiclassical methods and nonlinear sigma model calculations. We apply these results in open dots to extract the dephasing rate of electrons within the dot. In the tunneling regime, electron interaction dominates transport since the tunneling of a single electron onto a small dot may be sufficiently energetically costly (due to the small capacitance) that conduction is suppressed altogether. How interactions combine with quantum interference are best seen in this regime.Comment: 15 pages, 11 figures, PDF 2.1 format, to appear in "Chaos, Solitons & Fractals

The embedding method beyond the single-channel case: Two-mode and Hubbard chains

We investigate the relationship between persistent currents in multi-channel rings containing an embedded scatterer and the conductance through the same scatterer attached to leads. The case of two uncoupled channels corresponds to a Hubbard chain, for which the one-dimensional embedding method is readily generalized. Various tests are carried out to validate this new procedure, and the conductance of short one-dimensional Hubbard chains attached to perfect leads is computed for different system sizes and interaction strengths. In the case of two coupled channels the conductance can be obtained from a statistical analysis of the persistent current or by reducing the multi-channel scattering problem to several single-channel setups.Comment: 14 pages, 13 figures, submitted for publicatio