Prolapse of Intussusception through the Anus as a Result of Sigmoid Colon Cancer

Adult intussusception is rare and most often associated with cancer. We report a case of intussuscepted sigmoid colon into the rectum protruding from the anus of a 47-year-old woman. The cause of the intussusception was sigmoid colon cancer. We removed the intussuscepted part of the sigmoid colon as well as the rectum and regional lymph nodes. The patient recovered uneventfully and there has been no evidence of recurrence of the cancer

Engineering an aldehyde dehydrogenase toward its substrates, 3-hydroxypropanal and NAD(+), for enhancing the production of 3-hydroxypropionic acid

3-Hydroxypropionic acid (3-HP) can be produced via the biological route involving two enzymatic reactions: dehydration of glycerol to 3-hydroxypropanal (3-HPA) and then oxidation to 3-HP. However, commercial production of 3-HP using recombinant microorganisms has been hampered with several problems, some of which are associated with the toxicity of 3-HPA and the efficiency of NAD(+) regeneration. We engineered a-ketoglutaric semialdehyde dehydrogenase (KGSADH) from Azospirillum brasilense for the second reaction to address these issues. The residues in the binding sites for the substrates, 3-HPA and NAD(+), were randomized, and the resulting libraries were screened for higher activity. Isolated KGSADH variants had significantly lower Km values for both the substrates. The enzymes also showed higher substrate specificities for aldehyde and NAD(+), less inhibition by NADH, and greater resistance to inactivation by 3-HPA than the wild-type enzyme. A recombinant Pseudomonas denitrificans strain with one of the engineered KGSADH variants exhibited less accumulation of 3-HPA, decreased levels of inactivation of the enzymes, and higher cell growth than that with the wild-type KGSADH. The flask culture of the P. denitrificans strain with the mutant KGSADH resulted in about 40% increase of 3-HP titer (53 mM) compared with that using the wild-type enzyme (37 mM)

Runt-Related Transcription Factor 1 Regulates Luteinized Hormone-Induced Prostaglandin-Endoperoxide Synthase 2 Expression in Rat Periovulatory Granulosa Cells

Runt-related transcription factor 1 (RUNX1), a transcription factor, is transiently induced by the LH surge and regulates gene expression in periovulatory granulosa cells. Potential binding sites for RUNX are present in the 5′-flanking region of the Ptgs2 (prostaglandin-endoperoxide synthase 2) gene. Periovulatory Ptgs2 expression is essential for ovulation. In the present study, we investigated the role of RUNX1 in mediating the LH-induced expression of Ptgs2 in periovulatory granulosa cells. We first determined whether the suppression of Runx1 expression or activity affects Ptgs2 expression using cultured preovulatory granulosa cells isolated from immature rat ovaries primed with pregnant mare serum gonadotropin for 48 h. Knockdown of human chorionic gonadotropin-induced Runx1 expression by small interfering RNA or inhibition of endogenous RUNX activities by dominant-negative RUNX decreased human chorionic gonadotropin or agonist-stimulated Ptgs2 expression and transcriptional activity of Ptgs2 promoter reporter constructs. Results from chromatin immunoprecipitation assays revealed in vivo binding of endogenous RUNX1 to the Ptgs2 promoter region in rat periovulatory granulosa cells. Direct binding of RUNX1 to two RUNX-binding motifs in the Ptgs2 promoter region was confirmed by EMSA. The mutation of these two binding motifs resulted in decreased transcriptional activity of Ptgs2 promoter reporter constructs in preovulatory granulosa cells. Taken together, these findings provide experimental evidence that the LH-dependent induction of Ptgs2 expression results, in part, from RUNX1-mediated transactivation of the Ptgs2 promoter. The results of the present study assign potential significance for LH-induced RUNX1 in the ovulatory process via regulating Ptgs2 gene expression

P2X receptor subtype-specific modulation of excitatory and inhibitory synaptic inputs in the rat brainstem

The role of P2 receptors in synaptic transmission to the rat medial nucleus of the trapezoid body (MNTB) was studied in an in vitro brain slice preparation. Whole-cell patch recordings were made and spontaneous synaptic responses studied under voltage clamp during application of P2X receptor agonists. ATPγS (100 μm) had no effect on holding current, but facilitated spontaneous excitatory postsynaptic current (sEPSC) frequency in 41% of recordings and facilitated spontaneous inhibitory postsynaptic currents (sIPSCs) in 20% of recordings. These were blocked by the P2 receptor antagonist suramin (100 μm). α,β-meATP also facilitated sEPSC and sIPSC frequency, while l-β,γ-meATP facilitated only sIPSCs. The sEPSC facilitation by ATPγS was blocked by TTX (but did not block facilitation of sIPSCs). sEPSC facilitation was blocked by PPADS (30 μm) and the selective P2X(3) receptor antagonist A-317491 (3 μm), suggesting that modulation of sEPSCs involves P2X(3) receptor subunits. α,β-meATP-facilitated sIPSCs were also recorded in wild-type mouse MNTB neurones, but were absent in the MNTB from P2X(1) receptor-deficient mice demonstrating a functional role for P2X(1) receptors in the CNS