The Endocannabinoid 2-Arachidonoylglycerol Produced by Diacylglycerol Lipase α Mediates Retrograde Suppression of Synaptic Transmission

SummaryEndocannabinoids are released from postsynaptic neurons and cause retrograde suppression of synaptic transmission. Anandamide and 2-arachidonoylglycerol (2-AG) are regarded as two major endocannabinoids. To determine to what extent 2-AG contributes to retrograde signaling, we generated and analyzed mutant mice lacking either of the two 2-AG synthesizing enzymes diacylglycerol lipase α (DGLα) and β (DGLβ). We found that endocannabinoid-mediated retrograde synaptic suppression was totally absent in the cerebellum, hippocampus, and striatum of DGLα knockout mice, whereas the retrograde suppression was intact in DGLβ knockout brains. The basal 2-AG content was markedly reduced and stimulus-induced elevation of 2-AG was absent in DGLα knockout brains, whereas the 2-AG content was normal in DGLβ knockout brains. Morphology of the brain and expression of molecules required for 2-AG production other than DGLs were normal in the two knockout mice. We conclude that 2-AG produced by DGLα, but not by DGLβ, mediates retrograde suppression at central synapses

The Clathrin Assembly Protein PICALM Is Required for Erythroid Maturation and Transferrin Internalization in Mice

Phosphatidylinositol binding clathrin assembly protein (PICALM), also known as clathrin assembly lymphoid myeloid leukemia protein (CALM), was originally isolated as part of the fusion gene CALM/AF10, which results from the chromosomal translocation t(10;11)(p13;q14). CALM is sufficient to drive clathrin assembly in vitro on lipid monolayers and regulates clathrin-coated budding and the size and shape of the vesicles at the plasma membrane. However, the physiological role of CALM has yet to be elucidated. Here, the role of CALM in vivo was investigated using CALM-deficient mice. CALM-deficient mice exhibited retarded growth in utero and were dwarfed throughout their shortened life-spans. Moreover, CALM-deficient mice suffered from severe anemia, and the maturation and iron content in erythroid precursors were severely impaired. CALM-deficient erythroid cells and embryonic fibroblasts exhibited impaired clathrin-mediated endocytosis of transferrin. These results indicate that CALM is required for erythroid maturation and transferrin internalization in mice

Clinical factor associated with congenital cytomegalovirus infection in pregnant women with non-primary infection

The aim of this nested case-control study was to evaluate clinical factors associated with the occurrence of congenital cytomegalovirus (CMV) infection in pregnant women with non-primary CMV infection. In a cohort study of CMV screening for 2193 pregnant women and their newborns, seven newborns with congenital CMV infection were identified among 1287 pregnant women with non-primary CMV infection that was defined as negative IgM and positive IgG with IgG avidity index >45%. In the 1287 women with non-primary CMV infection, clinical findings and complications were compared between pregnancies with and without congenital CMV infection. Clinical factors associated with the occurrence of congenital CMV infection were evaluated. The birth weight of newborns with congenital CMV infection was less than that of newborns without congenital infection (p < 0.05). Univariate logistic regression analyses demonstrated that threatened premature delivery (OR 10.6, 95%CI 2.0–55.0; p < 0.01) and multiple pregnancy (OR 7.1, 95%CI 1.4–37.4; p < 0.05) were associated with congenital infection. Multivariable logistic regression analyses demonstrated that threatened premature delivery (OR 8.4, 95%CI 1.5–48.1; p < 0.05) was a single risk factor for congenital CMV infection in pregnant women with non-primary CMV infection. This study revealed for the first time that threatened premature delivery was associated with the occurrence of congenital CMV infection in pregnant women with non-primary CMV infection, the pathophysiology of which may be closely associated with CMV reactivation during pregnancy

The Role of Heme Oxygenase-1 Promoter Polymorphisms in Perinatal Disease

Heme oxygenase (HO) is the rate-limiting enzyme in the heme catabolic pathway, which degrades heme into equimolar amounts of carbon monoxide, free iron, and biliverdin. Its inducible isoform, HO-1, has multiple protective functions, including immune modulation and pregnancy maintenance, showing dynamic alteration during perinatal periods. As its contribution to the development of perinatal complications is speculated, two functional polymorphisms of the HMOX1 gene, (GT)n repeat polymorphism (rs3074372) and A(-413)T single nucleotide polymorphism (SNP) (rs2071746), were studied for their association with perinatal diseases. We systematically reviewed published evidence on HMOX1 polymorphisms in perinatal diseases and clarified their possible significant contribution to neonatal jaundice development, presumably due to their direct effect of inducing HO enzymatic activity in the bilirubin-producing pathway. However, the role of these polymorphisms seems limited for other perinatal complications such as bronchopulmonary dysplasia. We speculate that this is because the antioxidant or anti-inflammatory effect is not directly mediated by HO but by its byproducts, resulting in a milder effect. For better understanding, subtyping each morbidity by the level of exposure to causative environmental factors, simultaneous analysis of both polymorphisms, and the unified definition of short and long alleles in (GT)n repeats based on transcriptional capacity should be further investigated

Prophylactic Intravenous Immunoglobulin Injections to Mothers with Primary Cytomegalovirus Infection

The aim of this trial study was to assess the preventive efficacy of immunoglobulin with a high titer of anti-CMV antibody for mother-to-fetus cytomegalovirus (CMV) transmission among pregnant women with primary/acute CMV infection. The primary CMV infection in mothers was diagnosed by a positive test for CMV IgM and/or low IgG avidity. Intact type immunoglobulin with a high titer of anti-CMV antibody was injected intravenously at a dosage of 2.5-5.0 g/day for consecutive 3 days to mothers with primary CMV infection. Four pregnant women were enrolled. One pregnancy ended in no congenital infection, while two pregnancies ended in congenital CMV infection. The other one pregnancy was terminated. The mother-to-fetus CMV transmission rate was found to be high as 66.7% (2/3). This preliminary result suggests that intravenous immunoglobulin injections are not effective for the prevention of mother-to-fetus CMV transmission in the present protocol

Evaluation of the delta-shaped anastomosis in laparoscopic distal gastrectomy: midterm results of a comparison with Roux-en-Y anastomosis

Various methods of reconstruction after laparoscopic distal gastrectomy (LDG) have been developed and published, whereas only a limited number of reports are available on the utility of the delta-shaped anastomosis (Delta). This study compared Delta and Roux-en-Y anastomoses (RY), with the aim to clarify the utility of Delta. Stage 1 gastric cancer patients who had undergone LDG with Delta (group D, n = 68) and those who had undergone LDG with RY (group RY, n = 60) were compared in terms of operative outcomes, postoperative clinical symptoms, gastrointestinal fiberscopic findings, and changes in body weight. Both the operative and anastomotic times were significantly shorter in group D (230 and 13 min, respectively) than in group RY (258 and 38 min, respectively) (p < 0.001). Among the complications observed at the anastomotic site, obstruction was seen in one group D patient and two group RY patients but was relieved with conservative management. Postoperative clinical symptoms were reported for 26.4 % of the group D patients but had decreased to 5.9 % 1 year later. Group RY yielded similar results. Upper gastrointestinal fiberscopy performed 1 year postoperatively showed no intergroup differences in the incidence of gastritis or residual retention and a significantly more frequent occurrence of bile reflux in group D. Postoperative weight changes did not differ between the two groups. Delta reconstruction after LDG is a safe and effective procedure that is totally laparoscopic, less time consuming, and associated with a favorable postoperative course and a better quality of life

Fetal Ultrasound and Magnetic Resonance Imaging Abnormalities in Congenital Cytomegalovirus Infection Associated with and without Fetal Growth Restriction

Congenital cytomegalovirus infection (cCMV) can cause fetal growth restriction (FGR) and severe sequelae in affected infants. Clinicians generally suspect cCMV based on multiple ultrasound (US) findings associated with cCMV. However, no studies have assessed the diagnostic accuracy of fetal US for cCMV-associated abnormalities in FGR. Eight FGR and 10 non-FGR fetuses prenatally diagnosed with cCMV were examined by undergoing periodic detailed US examinations, as well as postnatal physical and imaging examinations. The diagnostic accuracy of prenatal US for cCMV-associated abnormalities was compared between FGR and non-FGR fetuses with cCMV. The diagnostic sensitivity rates of fetal US for cCMV-related abnormalities in FGR vs. non-FGR fetuses were as follows: ventriculomegaly, 66.7% vs. 88.9%; intracranial calcification, 20.0% vs. 20.0%; cysts and pseudocysts in the brain, 0% vs. 0%; ascites, 100.0% vs. 100.0%; hepatomegaly, 40.0% vs. 100.0%; splenomegaly, 0% vs. 0%. The diagnostic sensitivity of fetal US for hepatomegaly and ventriculomegaly in FGR fetuses with cCMV was lower than that in non-FGR fetuses with cCMV. The prevalence of severe long-term sequelae (e.g., bilateral hearing impairment, epilepsy, cerebral palsy, and severe developmental delay) in the CMV-infected fetuses with FGR was higher, albeit non-significantly. Clinicians should keep in mind the possibility of overlooking the symptoms of cCMV in assessing fetuses with FGR