Mesp1-nonexpressing cells contribute to the ventricular cardiac conduction system.

Previous fate mapping analysis, using Cre recombinase driven by the Mesp1 locus, revealed that Mesp1 is expressed in almost all of the precursors of the cardiovascular system, including the endothelium, endocardium, myocardium, and epicardium. Mesp1-nonexpressing cells were found to be restricted to the outflow tract cushion and along the interventricular septum (IVS), which is a location that is suggestive of specialized cardiac conduction system (CCS). In our current study, we examined the identity of these IVS cells by using the pattern of beta-galactosidase activity in CCS-lacZ mice. In addition, by crossing Mesp1-Cre and floxed GFP reporter mice with CCS-lacZ mice, we have calculated that approximately 20% of the ventricular CCS within the IVS corresponds to Mesp1-nonexpressing cells. These data suggest that the ventricular CCS is of heterocellular origin. Furthermore, we indicate a possibility that a population of the cells that contribute to the ventricular CCS might be distinguished at an early stage of development.     

The Effect of Continuous Intake of Lactobacillus gasseri OLL2716 on Mild to Moderate Delayed Gastric Emptying: A Randomized Controlled Study

Probiotics have been suggested to be effective for functional dyspepsia, but their effect on gastric motility is not clear. We evaluated the effect of Lactobacillus gasseri OLL2716 (LG21 strain) on mild to moderate delayed gastric emptying by a double-blind, parallel-group, placebo-controlled, randomized trial. Participants (n = 28) were randomly assigned to ingest LG21 strain-containing yogurt (LG21 strain group) or LG21 strain-free yogurt (placebo group) for 12 weeks. The ¹³C gastric emptying breath test was performed to measure the gastric emptying rate over time following ingestion of a liquid meal, and the time to reach the peak (Tmax) was used as an indicator of gastric emptying. We also measured the salivary amylase concentration, an indicator of autonomic dysfunction under stress. The per-protocol population (n = 27, male n = 4, female n = 23) was evaluated for efficacy. When a ≥30% reduction in the difference between participant’s Tmax and the Japanese mean Tmax was defined as an improvement, the odds ratio of improvement in delayed gastric emptying compared to placebo after 12 weeks was 4.1 (95% confidence interval, 0.8 to 20.2). Moreover, salivary amylase concentrations were significantly lower than in the placebo group, indicating an improvement in autonomic function. The present data were not enough to support the beneficial effects of the LG21 strain on delayed gastric emptying. However, if we define the odds ratio in further study investigated with a larger number of participants, LG21 strain might be expected to have some impact on delayed gastric emptying.     

Antinociceptive effects of ONO-9902, an enkephalinase inhibitor,after visceral stress condition in rats

Purpose

The present study was designed to examine the antinociceptive effects of orally administered ONO-9902, an enkephalinase inhibitor, on both somatic and visceral pain after visceral stress conditions.

Methods

Twenty six male rats were examined. Tail-flick (TF) and colorectal distension (CD) tests were used to determine somatic and visceral antinociceptive effects, respectively. Measurements were performed in rats under immediate post-stress conditions (group ST; n = 14) and in rats nor under stress conditions (group NST; n = 12). In the stressed group, the same device, CD, for visceral antinociceptive effects was used for visceral stress and was applied with an intracolonic pressure of 60 mmHg for 20 min after drug administration. The TF latency and CD threshold were measured before and at 30, 40, 50, 60 and 90 min after administration of ONO-9902 300 mg · kg^?1 or distilled water.

Results

Orally administered ONO-9902 did not produce any changes in the % maximum possible effect (%MPE) in either TF or CD tests in the unstressed group. In the stressed group, %MPE in the CD test increased 18% and 31% at 30 and 40 min, respectively, after oral administration of ONO-9902 compared with the control group (P < 0.05). However, %MPE to TF test did not alter even after the CD-induced stress condition.

Conclusion

These results suggest that ONO-9902 may have analgesic effects on visceral pain but not on somatic pain under immediate post-stress conditions.     

Effects of dorzolamide hydrochloride on ocular tissues.

We studied the intraocular pharmacokinetics of dorzolamide hydrochloride eye drops and the effect of dorzolamide on carbonic anhydrase activity and localization in ocular tissues. Carbonic anhydrase activity was detected in normal ocular tissues. The activity was inhibited in corneal endothelial cells, the ciliary body, lens epithelial cells, or the retina 1 to 8 hours after instillation of dorzolamide eye drops. In lens epithelial cells and the retina, the enzyme activity had not recovered even 10 hours after instillation of the drug. Immunostaining did not reveal any differences between the group administered dorzolamide eye drops and the control group administered a physiologically balanced solution. Time-related changes in dorzolamide concentrations in ocular tissues were measured by high-performance liquid chromatography (HPLC). In the cornea, anterior aqueous, iris, ciliary body and retina, drug concentrations increased 15 minutes after the instillation and peaked within 1 hour. These results suggest that dorzolamide immediately suppresses carbonic anhydrase activity in ocular tissues, and is rapidly distributed among the tissues of the eye when administered as eye drops.     

Identification of CCND3 and BYSL as candidate targets for the 6p21 amplification in diffuse large B-cell lymphoma.

PURPOSE: Increases in gene dosage through DNA amplification represents a common feature of many tumors and can result in the up-regulation of tumor-promoting genes. Our recent genome-wide, array-based comparative genomic hybridization analysis of 66 cases of diffuse large B-cell lymphoma found that genomic gain of 6p21 was observed in as many as 17 cases, including 14 cases with low-level copy number gain and three cases with high-level copy number gains (amplifications). EXPERIMENTAL DESIGN AND RESULTS: To identify the target gene(s) for 6p21 amplification, we constructed a detailed amplicon map at the region of genomic amplification with the aid of high-resolution contig array-based comparative genomic hybridization glass slides, consisting of contiguously ordered bacterial artificial chromosome/P1-derived artificial chromosome clones covering 3 Mb throughout the 6p21 amplification region. Alignment of the amplifications identified a minimally overlapping 800 kb segment containing 15 genes. Quantitative expression analysis of the genes from both patient samples and the SUDHL9 cell line revealed that CCND3 and BYSL (1.9 kb telomeric to the CCND3 gene locus) are the targets of 6p21 genomic gain/amplification. CONCLUSIONS: Although it is known that t(6;14)(p21;q32) induces aberrant overexpression of CCND3 in B-cell malignancies, we were able to show that CCND3, which encodes the cyclin D family member protein that controls the G1-S phase of cell cycle regulation, can also be a target of genomic gain/amplification. Overexpression of CCND3 through genomic amplification is likely to lead to aberrant cell cycle control, although the precise biological role of BYSL with respect to tumorigenesis remains to be determined.     

Smoking Exposure Is Associated with Serum Vitamin D Deficiency in Children: Evidence from the Japan Environment and Children’s Study

Tobacco smoke exposure is known to lower serum 25-hydroxyvitamin D (25(OH)D) concentrations. This study evaluated the association between passive smoking and vitamin D deficiency (VDD) in young children using data from the Japan Environment and Children’s Study (JECS), the largest birth cohort study in Japan. Information on parental smoking status was extracted from a survey of JECS for children aged 1.5 years and data for serum 25(OH)D concentrations were obtained from blood tests in the Sub-Cohort Study of JECS performed at age 2 years. Logistic regression and linear models were fitted to evaluate the association between these variables. Data were analyzed for 4593 children. After adjusting for covariates, smoke exposure was significantly associated with increased incidence of VDD (OR 1.35; 95% CI, 1.14–1.59) according to the logistic model. The linear model indicated that passive smoking negatively predicted de-seasonalized serum 25(OH)D concentrations (β −0.5; 95% CI −0.95 to −0.08) in children aged 2 years. The results suggest that smoke exposure is a risk factor for VDD in children. Given that VD plays a crucial role in bone metabolism and the immune system, our findings are significant for clinical and public health.     

Pipeline Flex with Shield Technology Placement for Small- and Medium-sized Aneurysms Achieves Early Complete Occlusion

The flow diverter has been shown to be a safe and effective device for large cerebral aneurysms in the proximal internal carotid artery (ICA). Recently, its indication has been expanded to small- and medium-sized cerebral aneurysms in the distal segment of the ICA. In this study, we report a single-center, retrospective investigation of the safety and efficacy of the Pipeline Flex device to treat these aneurysms. Of the patients who underwent Pipeline implantation for small- and medium-sized ICA aneurysms (≤12 mm) at our hospital between July 2013 and October 2021, 102 patients with 104 aneurysms were included in this study. The mean age of the patients was 57.7 ± 12.1 years, and 94 (90.4%) were female. The mean aneurysmal dome diameter was 9.2 ± 2.3 mm, the mean neck diameter was 5.3 ± 1.6 mm, and the mean dome-to-neck ratio was 1.8 ± 0.5. Twenty-five patients (24.0%) had incorporated vessels from the aneurysm. Complete occlusion of the aneurysms was obtained in 96 patients (92.3%). There were no cases of parent artery stenosis or major stroke after the procedure. Absence of incorporated vessel from the aneurysm dome and adjunctive coil embolization are statistically significant factors indicating complete occlusion in multivariate analysis. The time to complete occlusion was determined earlier with the use of the Pipeline Shield (p = 0.0386) and with adjunctive coils (p = 0.0025). We showed that Pipeline implantation for small- and medium-sized aneurysms was safe and highly effective.