SLCO1B1 and SLCO1B3 genetic mutations in Taiwanese patients with Rotor syndrome.

Rotor syndrome is a rare, benign, inherited disorder that is commonly associated with mild hyperbilirubinemia. It is caused by bi-allelic pathological variants in both SLCO1B1 and SLCO1B3 genes, causing defective OATP1B1 and OATP1B3 in the sinusoidal membrane and interrupted bilirubin uptake of the hepatocytes. We report five Taiwanese pediatric and adult patients aged 5-32 years presenting with conjugated hyperbilirubinemia, and were found to have genetic variants of SLCO1B1 and SLCO1B3. Two also had history of prolonged neonatal jaundice. Genetic analysis using panel-based next generation sequencing revealed three patients with homozygous mutations c.1738C>T (p.R580∗) in SLCO1B1 and a transposon LINE-1 insertion in SLCO1B3, one patient with homozygous mutations for another haplotype, c.757C>T (p.R253∗) in SLCO1B1 and c.1747+1G>A in SLCO1B3. Another patient had heterozygous c.1738C>T (p.R580∗) in SLCO1B1 linked with a LINE-1 insertion in SLCO1B3, and heterozygous c.757C>T (p.R253∗) in SLCO1B1 linked with c.1747+1G>A in SLCO1B3. In conclusion, we present the first time of genetic diagnosis of Rotor syndrome in Taiwan. Advanced genetic testing has enhanced the diagnosis of rare diseases with mild symptoms.

Apoptosis-related phenotype of ejaculated spermatozoa in patients with varicocele.

OBJECTIVE: To determine the integrity of the sperm plasma membrane, mitochondria, and DNA, which are essential for accurate transmission of genetic material to offspring, and to quantify possible apoptosis and investigate any relationship between these parameters in ejaculated sperm from men with or without varicoceles. DESIGN: Retrospective study. SETTING: University teaching hospital. PATIENT(S): Twenty-five patients with varicocele and 10 normal, fertile controls. INTERVENTION(S): Apoptosis-related phenotype activations including the plasma membrane translocation of phosphatidylserine, mitochondrial dysfunction, and nuclear DNA damage, were assessed by using the annexin-V/propidium iodide double staining assay, 3,3'-dihexloxacarbocyanine iodide staining assay, and single-cell gel electrophoresis assay (comet assay). MAIN OUTCOME MEASURE(S): Apoptosis-related phenotype. RESULT(S): Patients with varicocele had statistically significantly more annexin V live sperm cells and nuclear DNA fragmentation than did the control men. In contrast, their numbers of 3,3'-dihexloxacarbocyanine iodide live cells were statistically significantly less than those in control men. CONCLUSION(S): The increased externalization of phosphatidylserine, mitochondrial dysfunction, and nuclear DNA damage occurred in the sperm of men with varicoceles, suggesting that certain apoptotic mechanisms may relate to the condition of varicocele, originating in the mitochondria of spermatocytes and then functioning within the nucleus of the cell.

Apoptosis of T-leukemia and B-myeloma cancer cells induced by hyperbaric oxygen increased phosphorylation of p38 MAPK.

Tumor cells with different origins have different threshold to apoptosis. Hematopoietic (Jurkat, NCI-H929) cells and non-hematopoietic (A549, MCF-7) cells were received hyperbaric oxygen (HBO(2)) treatment from 2.5 to 3.5 atmosphere absolute (ATA) of 100% oxygen for 6h, and a significant percentage of apoptosis were shown only in hematopoietic Jurkat and NCI-H929 cells by either Annexin V or TUNEL assay. Oxidative stress was illustrated higher in HBO(2)-treated hematopoietic cells by superoxide fluorochrome detectors. HBO(2) treatment leads to caspase-3, caspase-7 activation and further cleavage of PARP within cells. Furthermore, the increased phosphorylation of p38 MAPK was demonstrated in both Jurkat and NCI-H929 cells.