Long-term Ultrasonographic Follow-up Study of Gastric Motility in Patients with Functional Dyspepsia

Although patients with functional dyspepsia complain of epigastric symptoms, the relation between these symptoms and gastric motility remains controversial. There are few reports on the clinical course of functional dyspepsia, including changes in gastric motility, observed over a considerably long period. We conducted a study to examine association between changes in symptoms and changes in ultrasonographically evaluated gastric motility over a long-term follow-up period in patients with functional dyspepsia. Forty patients (18 men, 22 women; mean age, 53.7 years) with functional dyspepsia were followed up by medical interview, physical examination, endoscopy, and ultrasonography for gastric motility. Follow-up ranged from 1.0 to 7.8 years (mean, 3.0 years). Ultrasonographic evaluation of gastric motility included gastric emptying rate and antral contractions. During the follow-up period, patients were treated with proton pump inhibitors, H2-blockers, or prokinetics. Symptoms improved in 21 patients (group A), but symptoms persisted or worsened in 19 patients (group B). There were no significant differences in clinical characteristics between the two groups. Gastric motility improved in group A but not in group B. In conclusion, improved gastric motility appears to correspond to and may explain improved symptoms in some patients with functional dyspepsia

トクシマハツ ノ リンショウ オウヨウ オ メザシタ キソ ケンキュウ : トランスレーショナル リサーチ オ シヤ ニ イレタ ショウホウ ユソウ ケンキュウ

Transfer of proteins and lipids by means of small, membrane-bound vesicles within the cell is essential for virtually all cell functions. Defects in targeting functional molecules to the appropriate destinations can render cells non-functional, thereby causing diseases. The Rab small G protein family (Rab) consists of over sixty members, and is implicated in intracellular vesicle transport, which includes exocytosis, endocytosis, and transcytosis. Rab cycles between the GDP-bound inactive form and the GTP-bound active form and translocates between the cytosol and the membranes, and these cyclical activation, inactivation, and translocation processes are regulated by at least three types of regulatory proteins (GDI, GEP, GAP). The GTP-bound form then interacts with downstream effectors and functions through them. Evidence is accumulating that Rab is a key molecule to clarify molecular physiology and pathophysiology of vesicle transport

Proximal Vertebral Body Fracture after 4-Level Fusion Using L1 as the Upper Instrumented Vertebra for Lumbar Degenerative Disease: Report of 2 Cases with Literature Review

Some cases with lumbar degenerative diseases require multi-level fusion surgeries. At our institute, 27 and 4 procedures of 3- and 4-level fusion were performed out of a total 672 posterior lumbar interfusions (PLIFs) on patients with lumbar degenerative disease from 2005 to 2010. We present 2 osteoporotic patients who developed proximal vertebral body fracture after 4-level fusion. Both cases presented with gait disability for leg pain by degenerative lumbar scoliosis and canal stenosis at the levels of L1/2-4/5. After 4-level fusion using L1 as the upper instrumented vertebra, proximal vertebral body fractures were found along with the right pedicle fractures of L1 in both cases. One of these patients, aged 82 years, was treated as an outpatient using a hard corset for 24 months, but the fractures were exacerbated over time. In the other patient, posterolateral fusion was extended from Th10 to L5. Both patients can walk alone and have been thoroughly followed up. In both cases, the fracture of the right L1 pedicle might be related to the subsequent fractures and fusion failure. In consideration of multi-level fusion, L1 should be avoided as an upper instrumented vertebra to prevent junctional kyphosis, especially in cases with osteoporosis and flat back posture

Increased Systemic Glucose Tolerance with Increased Muscle Glucose Uptake in Transgenic Mice Overexpressing RXRγ in Skeletal Muscle

BACKGROUND: Retinoid X receptor (RXR) γ is a nuclear receptor-type transcription factor expressed mostly in skeletal muscle, and regulated by nutritional conditions. Previously, we established transgenic mice overexpressing RXRγ in skeletal muscle (RXRγ mice), which showed lower blood glucose than the control mice. Here we investigated their glucose metabolism. METHODOLOGY/PRINCIPAL FINDINGS: RXRγ mice were subjected to glucose and insulin tolerance tests, and glucose transporter expression levels, hyperinsulinemic-euglycemic clamp and glucose uptake were analyzed. Microarray and bioinformatics analyses were done. The glucose tolerance test revealed higher glucose disposal in RXRγ mice than in control mice, but insulin tolerance test revealed no difference in the insulin-induced hypoglycemic response. In the hyperinsulinemic-euglycemic clamp study, the basal glucose disposal rate was higher in RXRγ mice than in control mice, indicating an insulin-independent increase in glucose uptake. There was no difference in the rate of glucose infusion needed to maintain euglycemia (glucose infusion rate) between the RXRγ and control mice, which is consistent with the result of the insulin tolerance test. Skeletal muscle from RXRγ mice showed increased Glut1 expression, with increased glucose uptake, in an insulin-independent manner. Moreover, we performed in vivo luciferase reporter analysis using Glut1 promoter (Glut1-Luc). Combination of RXRγ and PPARδ resulted in an increase in Glut1-Luc activity in skeletal muscle in vivo. Microarray data showed that RXRγ overexpression increased a diverse set of genes, including glucose metabolism genes, whose promoter contained putative PPAR-binding motifs. CONCLUSIONS/SIGNIFICANCE: Systemic glucose metabolism was increased in transgenic mice overexpressing RXRγ. The enhanced glucose tolerance in RXRγ mice may be mediated at least in part by increased Glut1 in skeletal muscle. These results show the importance of skeletal muscle gene regulation in systemic glucose metabolism. Increasing RXRγ expression may be a novel therapeutic strategy against type 2 diabetes

Influence of pneumonia complications on the prognosis of patients with autopsy-confirmed Alzheimer\u27s disease, dementia with Lewy bodies, and vascular dementia

BackgroundPneumonia is a major, complicated disease in patients with dementia. However, the influence of pneumonia on the prognosis of patients with varying types of dementia has not been fully evaluated.ResultsOf the 157 eligible patients, 63 (40.1%) had AD, 42 (26.8%) had DLB, and 52 (33.1%) had VaD. Pneumonia complication was observed with high incidence in each subtype of dementia, especially in DLB (90.5%). The median total duration from dementia onset to death was 8 years in AD and DLB, and 5 years in VaD. The VaD subtype had more male patients than AD or DLB (P = 0.010), and age of death in this group was the youngest among the three groups (P = 0.018). A significant difference was observed in the survival time by the Kaplan–Meier method among the three groups (P < 0.001) and among the groups with pneumonia (P = 0.002). The factors associated with shorter survival time were male gender, pneumonia complications, diabetes mellitus, age of dementia onset ≥ 75 years, and VaD.ConclusionsPneumonia complications shortened the survival time of patients with AD, DLB, and VaD

Yokukansan Inhibits Neuronal Death during ER Stress by Regulating the Unfolded Protein Response

Recently, several studies have reported Yokukansan (Tsumura TJ-54), a traditional Japanese medicine, as a potential new drug for the treatment of Alzheimer's disease (AD). Endoplasmic reticulum (ER) stress is known to play an important role in the pathogenesis of AD, particularly in neuronal death. Therefore, we examined the effect of Yokukansan on ER stress-induced neurotoxicity and on familial AD-linked presenilin-1 mutation-associated cell death.We employed the WST-1 assay and monitored morphological changes to evaluate cell viability following Yokukansan treatment or treatment with its components. Western blotting and PCR were used to observe the expression levels of GRP78/BiP, caspase-4 and C/EBP homologous protein.Yokukansan inhibited neuronal death during ER stress, with Cnidii Rhizoma (Senkyu), a component of Yokukansan, being particularly effective. We also showed that Yokukansan and Senkyu affect the unfolded protein response following ER stress and that these drugs inhibit the activation of caspase-4, resulting in the inhibition of ER stress-induced neuronal death. Furthermore, we found that the protective effect of Yokukansan and Senkyu against ER stress could be attributed to the ferulic acid content of these two drugs.Our results indicate that Yokukansan, Senkyu and ferulic acid are protective against ER stress-induced neuronal cell death and may provide a possible new treatment for AD

The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force

「コロナ制圧タスクフォース」COVID-19患者由来の血液細胞における遺伝子発現の網羅的解析 --重症度に応じた遺伝子発現の変化には、ヒトゲノム配列の個人差が影響する--. 京都大学プレスリリース. 2022-08-23.Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection