1. Single-unit recordings were obtained from the supplementary motor area of the cerebral cortex of two monkeys during execution of learned movements 2. Monkeys were required to push or pull a cast attached to the right forelimb in response to a sudden perturbation delivered via the cast. An instruction as to the direction of the monkey's movement was delivered 2.5--5 s prior to the occurrence of the perturbation and correct performance, therefore, required the animal to develop a preparatory state prior to the perturbation. 3. Of many hundreds of neurons recorded, 201 exhibited instruction-induced changes of activity during the period intervening between the instruction and the perturbation-triggered movement. 4. In 94 neurons, effects of the instruction were differential depending on which of the two instructions was given, whereas in 107 neurons, effects were nondifferential. The latencies of the differential responses appeared to be shorter (starting as early as 140 ms after the instruction). 5. The magnitude of the instruction effects varied in parallel with development of enhanced motor skill as the monkeys gained more experience in responding to the triggering stimulus. 6. These observations substantiate the hypothesis that the supplementary motor area plays a part in modifying a sensory-triggered motor output.
Lysophospholipid acyltransferases (LPLATs) regulate the diversification of fatty acid composition in biological membranes. Lysophosphatidylcholine acyltransferases (LPCATs) are members of the LPLATs that play a role in inflammatory responses. M1 macrophages differentiate in response to lipopolysaccharide (LPS) and are pro-inflammatory, whereas M2 macrophages, which differentiate in response to interleukin-4 (IL-4), are anti-inflammatory and involved in homeostasis and wound healing. In the present study, we showed that LPCATs play an important role in M1/M2-macrophage polarization. LPS changed the shape of PMA-treated U937 cells from rounded to spindle shaped and upregulated the mRNA and protein expression of the M1 macrophage markers CXCL10, TNF-α, and IL-1β. IL-4 had no effect on the shape of PMA-treated U937 cells and upregulated the M2 macrophage markers CD206, IL-1ra, and TGF-β in PMA-treated U937 cells. These results suggest that LPS and IL-4 promote the differentiation of PMA-treated U937 cells into M1- and M2-polarized macrophages, respectively. LPS significantly downregulated the mRNA expression of LPCAT3, one of four LPCAT isoforms, and suppressed its enzymatic activity toward linoleoyl-CoA and arachidonoyl-CoA in PMA-treated U937 cells. LPCAT3 knockdown induced a spindle-shaped morphology typical of M1-polarized macrophages, and increased the secretion of CXCL10 and decreased the levels of CD206 in IL-4-activated U937 cells. This indicates that knockdown of LPCAT3 shifts the differentiation of PMA-treated U937 cells to M1-polarized macrophages. Our findings suggest that LPCAT3 plays an important role in M1/M2-macrophage polarization, providing novel potential therapeutic targets for the regulation of immune and inflammatory disorders.
Objective: Inflammatory bowel disease, which frequently accompanies silencing of Mlh1, plays a key role in the pathogenesis of colorectal cancer. The interaction between inflammation and mismatch repair deficiency, however, remains unclear. The aim of this study was to determine the effect of inflammation on colorectal carcinogenesis in Mlh1-deficient mice. Method: Inflammatory colitis was induced by treatment with 1% dextran sodium sulfate (DSS) in drinking water for 1 week in Mlh1 knockout (Mlh1–/–), Mlh1 heterozygous (Mlh1+/–) and wild-type (Mlh1+/+) mice at 10 weeks of age. The development of colon tumors was followed for a subsequent 15 weeks and the tumors were analyzed immunohistochemically for the expression and localization of iNOS, β-catenin and p53. Results: Male and female Mlh1–/– mice with DSS showed a 63 and 44% incidence of tumors, respectively, whereas no tumors were observed in Mlh1+/– and Mlh1+/+ mice. The mice without DSS treatment did not develop any tumors regardless of the genotype. While aberrant expression of β-catenin was not detected in colonic neoplasms, p53 and iNOS expression was increased in 100 and 77%, respectively. These immunohistochemical changes were consistent with those of human colon cancers associated with ulcerative colitis. Conclusion: Our results indicate that Mlh1 deficiency strongly accelerates colon carcinogenesis when combined with inflammation. Thus the cells with Mlh1 deficiency, either inherently or colitis associated, may be at an increased risk of cancer under inflammatory conditions.
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Beauty and cuteness are considered to represent different aspects of attractiveness and to be distinguishable from each other by their respective reliance on neonate and sexually mature features found in attractive faces. In this study, we investigated whether baby schema features in adult faces affect not only cuteness, but also beauty and attractiveness. We also investigated possible differences among attractiveness, beauty, and cuteness, and possible effects of perceived youth on these judgments. Results showed that baby schema features affected judgments of attractiveness, beauty, and cuteness, but that perceived youth did not significantly influence these judgments. Furthermore, the effect of each facial feature differed across rating types with the participants’ naïve interpretation of rating categories. This suggests that beauty predominantly refers to sexual attraction, while attractiveness refers to a non-sexual attraction regardless of participants’ gender. However, gender differences may exist in judging cuteness. Therefore, expressions related to attractiveness may incorporate different elements and this distinction may not be fully shared across gender.
This report presents a rare case of intrahepatic cholangiocarcinoma (IHCC) arising 28 years after excision of a type IV-A congenital choledochal cyst. The patient underwent excision of a congenital choledochal cyst (Todani’s type IV-A) at 12 years of age, with Roux-en-Y hepaticojejunostomy reconstruction. She received a pancreaticoduodenectomy (PD) using the modified Child method for an infection of a residual congenital choledochal cyst in the pancreatic head at the age of 18. She was referred to this department with a liver tumor 22 years later. Left hemihepatectomy with left-side caudate lobectomy was performed and the tumor was pathologically diagnosed to be IHCC. The cause of the current carcinogenesis was presumed to be reflux of pancreatic juice into the residual intrahepatic bile duct during surgery. This case suggests that a careful long-term follow-up is important for patients with congenital choledochal cysts, even if a separation-operation was performed at a young age, and especially after PD.
We report our experience with radical transurethral resection of the prostate performed on 89 male spinal cord injury subjects. The over-all success rate of modified sphincterotomy was 90 per cent, although there was a 14 per cent recurrence rate with time. Urodynamically, success was characterized by a statistically significant reduction in the degree of detrusor-sphincter dyssynergia, an increase in vesical compliance and a reduction in detrusor hyperreflexia. These results suggest an effect on the distal sphincteric area by the adrenergic system in the genesis of detrusor-sphincter dyssynergia. It is suggested that radical transurethral resection of the prostate exerts this effect via a surgical sympathectomy, while continence is preserved by the activity of the untouched external urethral sphincter.
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