Wall thickness control in biotubes prepared using type-C mold

Journal of Artificial Organs - A type-C mold based on in-body tissue architecture was previously developed for preparing small-diameter biotube vascular grafts with a 2-mm diameter and...     

Somatic mosaic deletions involving SCN1A cause Dravet syndrome

Somatic mosaicism in single nucleotide variants of SCN1A is known to occur in a subset of parents of children with Dravet syndrome (DS). Here, we report recurrent somatic mosaic microdeletions involving SCN1A in children diagnosed with DS. Through the evaluation of 237 affected individuals with DS who did not show SCN1A or PCHD19 mutations in prior sequencing analyzes, we identified two children with mosaic microdeletions covering the entire SCN1A region. The allele frequency of the mosaic deletions estimated by multiplex ligation‐dependent probe amplification and array comparative genomic hybridization was 25–40%, which was comparable to the mosaic ratio in lymphocytes and buccal mucosa cells observed by fluorescence in situ hybridization analysis. The minimal prevalence of SCN1A mosaic deletion is estimated to be 0.9% (95% confidence level: 0.11–3.11%) of DS with negative for SCN1A and PCDH19 mutations. This study reinforces the importance of somatic mosaicism caused by copy number variations in disease‐causing genes, and provides an alternative spectrum of SCN1A mutations causative of DS. Somatic deletions in SCN1A should be considered in cases with DS when standard screenings for SCN1A mutations are apparently negative for mutations.

     

Antigen‐specific airway IL‐33 production depends on FcγR‐mediated incorporation of the antigen by alveolar macrophages in sensitized mice

Although interleukin (IL)‐33 is a candidate for the aggravation of asthma, the mechanisms underlying antigen‐specific IL‐33 production in the lung are unclear. Therefore, we analysed the mechanisms in mice. Intra‐tracheal administration of ovalbumin (OVA) evoked increases in IL‐33 and IL‐33 mRNA in the lungs of both non‐sensitized and OVA‐sensitized mice, and the increases in the sensitized mice were significantly higher than in the non‐sensitized mice. However, intra‐tracheal administration of bovine serum albumin did not increase the IL‐33 level in the OVA‐sensitized mice. Depletion of neither mast cells/basophils nor CD4⁺ cells abolished the OVA‐induced IL‐33 production in sensitized mice, suggesting that the antigen recognition leading to the IL‐33 production was not related with either antigen‐specific IgE‐bearing mast cells/basophils or memory CD4⁺ Th2 cells. When a fluorogenic substrate‐labelled OVA (DQ‐OVA) was intra‐tracheally administered, the lung cells of sensitized mice incorporated more DQ‐OVA than those of non‐sensitized mice. The lung cells incorporating DQ‐OVA included B‐cells and alveolar macrophages. The allergic IL‐33 production was significantly reduced by treatment with anti‐FcγRII/III mAb. Depletion of alveolar macrophages by clodronate liposomes significantly suppressed the allergic IL‐33 production, whereas depletion of B‐cells by anti‐CD20 mAb did not. These results suggest that the administered OVA in the lung bound antigen‐specific IgG Ab, and then alveolar macrophages incorporated the immune complex through FcγRII/III on the cell surface, resulting in IL‐33 production in sensitized mice. The mechanisms underlying the antigen‐specific IL‐33 production may aid in development of new pharmacotherapies.     

Effect of mother's voice on neonatal respiratory activity and EEG delta amplitude

While the influence of the mother's voice on neonatal heart‐rate response and its relevant activity on cerebral cortex and the autonomic nervous system (ANS) are well known, few studies have assessed its influence on respiratory activity. We investigated the relationship among the respiration rate, the delta wave amplitudes through electroencephalography, and the basal state of ANS through the respiratory variability index while 22 full‐term neonates hear their mother's voice and an unknown voice. It was found that when respiratory variability was large, a transient (<5 s) change in respiration rates was observed in response to an unknown voice, while a greater increase in the delta wave amplitude was observed in the frontal lobe than the parietal one in response to the mother's voice. Conversely, when respiratory variability was small, a sustained increase (>10 s) in respiration rates was observed in response to the mother's voice, while a greater increase in the delta wave amplitude was found in both the frontal and parietal lobes. These results suggest that the basal state of ANS influences the latency of increases in respiration rates. Furthermore, induced by the mother's voice, transient increases in respiration rates are reduced in association with frontal lobe activity, and sustained increases in respiration rates are promoted in association with frontal and parietal lobe activities.     

The association of hemoglobin A1c and high risk plaque and plaque extent assessed by coronary computed tomography angiography

The objective of this study was to investigate the relationship of Hemoglobin A1c (HbA1c) and plaque characteristics including high risk plaque and plaque extent. We retrospectively examined 1079 consecutive coronary computed tomography (CT) angiography scans and the HbA1c results. We divided the patients into four groups by the HbA1c status: non-diabetic, ≤6.0; borderline, 6.1–6.4; diabetic low, 6.5–7.1; diabetic high, >7.1. We determined segment involvement score >4 as extensive disease. High risk plaque was defined as two feature positive (FP) plaque which consists of positive remodeling (remodeling index >1.1) and low attenuation (<30 HU). Univariate and multivariate analysis including conventional cardiovascular risk factors, symptoms and medication was performed. Univariate analysis showed that diabetic patients as well as borderline patients were significantly related with 2FP plaque and extensive disease. Although the relationship of borderline patients and 2FP plaque was marginal in multivariate analysis [odds ratio (OR) 1.53, 95 % confidence interval (CI) 0.95–2.40, p = 0.07], the elevation of HbA1c was strongly associated with 2FP plaque (diabetic low, OR 2.19, 95 % CI 1.37–3.45, p < 0.005; diabetic high, OR 4.14, 95 % CI 2.57–6.67, p < 0.0005). The association of HbA1c elevation and extensive disease was quite similar between borderline and diabetic patients (borderline, OR 1.96, 95 % CI 1.29–2.95, p < 0.005; diabetic low, OR 1.94, 95 % CI 1.25–3.01, p < 0.005; diabetic high, OR 2.19, 95 % CI 1.39–3.43, p < 0.005). Patients with elevated HbA1c of >6.0 are potentially at risk for future cardiovascular events due to increased high risk plaque and extensive disease, even below the diabetic level of 6.5. Coronary CT could be used for risk stratification of these patients.     

Alterations in serum amino acid concentrations in male and female schizophrenic patients

BACKGROUND: Since several studies have investigated gender-related differences in the onset of disease, response to drug therapy, etc. in schizophrenic patients, we examined the alterations in serum amino acids concentrations in male and female patients separately. METHODS: Serum amino acid concentrations in the normal (n=35; male 21 and female 14) and schizophrenic patients (n=32; male 19 and female 13) were determined by HPLC using a pre-column fluorescence derivatization with 4-fluoro-7-nitro-2,1,3-benzoxadiazole. RESULTS: Serum glutamate and serine concentrations were significantly increased in the male schizophrenic patients (p=0.0161 and 0.0257, respectively), while the serum Pro concentration was significantly increased in female schizophrenic patients (p=0.0398). Serum Glu, Ser, and Pro concentrations in the patients did not significantly correlate with the age, age of onset of disease, duration of illness, and chlorpromazine equivalents. Among the amino acids, serum Orn concentrations in male and female schizophrenic patients positively correlated with the duration of illness (p<0.01, r=0.685 and 0.688, respectively). CONCLUSION: The present data suggest the existence of gender-related differences in the alterations in serum amino acid concentrations in schizophrenic patients; further, serum Orn concentration in both sexes might be influenced by medications.     

Osteoclasts are dispensable for hematopoietic stem cell maintenance and mobilization

Hematopoietic stem cells (HSCs) are maintained in a specific bone marrow (BM) niche in cavities formed by osteoclasts. Osteoclast-deficient mice are osteopetrotic and exhibit closed BM cavities. Osteoclast activity is inversely correlated with hematopoietic activity; however, how osteoclasts and the BM cavity potentially regulate hematopoiesis is not well understood. To investigate this question, we evaluated hematopoietic activity in three osteopetrotic mouse models: op/op, c-Fos-deficient, and RANKL (receptor activator of nuclear factor kappa B ligand)-deficient mice. We show that, although osteoclasts and, by consequence, BM cavities are absent in these animals, hematopoietic stem and progenitor cell (HSPC) mobilization after granulocyte colony-stimulating factor injection was comparable or even higher in all three lines compared with wild-type mice. In contrast, osteoprotegerin-deficient mice, which have increased numbers of osteoclasts, showed reduced HSPC mobilization. BM-deficient patients and mice reportedly maintain hematopoiesis in extramedullary spaces, such as spleen; however, splenectomized op/op mice did not show reduced HSPC mobilization. Interestingly, we detected an HSC population in osteopetrotic bone of op/op mice, and pharmacological ablation of osteoclasts in wild-type mice did not inhibit, and even increased, HSPC mobilization. These results suggest that osteoclasts are dispensable for HSC mobilization and may function as negative regulators in the hematopoietic system.     

Partial Trisomy 9p with Clinical Symptoms Resembling Interferonopathies

Journal of Clinical Immunology -     

Clinical characteristics of α-pyrrolidinovalerophenone (α-PVP) poisoning

Context: α-Pyrrolidinovalerophenone (α-PVP) is a synthetic cathinone that has been abused in recent years. The clinical presentation of acute α-PVP poisoning has not been well characterized.

Objective: To elucidate the clinical features of acute α-PVP poisoning.

Materials and methods: This retrospective case series included eight subjects that visited our hospital emergency department (ED) between March 2012 and November 2014 and had analytically confirmed blood α-PVP levels. Data related to subject demographics, clinical history, laboratory findings, blood drug levels, and outcome were collected.

Results: The median age of the eight study subjects was 27 (range; 21–63) years, and six were male. Drug preparations had been administered by rectal insertion (three subjects) or inhalation (five subjects). The time between drug exposure and presentation at the ED was 8.5 (1–24) h and blood α-PVP concentrations ranged from 1.0 to 52.5?ng/ml. Although psychiatric and neurological findings were reported before arrival at the ED in 5/8 and 7/8 subjects, respectively, these were only observed in 1/8 and 2/8 subjects, respectively, at the ED. Symptoms of high body temperature (3/8), tachycardia (5/8), hypertension (3/8), acid-base balance disorder (5/8), coagulopathy (4/6), blood creatinine phosphokinase?>190?U/l (6/8), and a blood lactate level?>?1.7?mmol/l (5/7) were observed. All subjects survived and were discharged.

Conclusions: This retrospective case series showed that after acute exposure to α-PVP, transient neuropsychiatric findings were accompanied by more persistent sympathomimetic physical findings, disorders of acid-base balance and blood coagulation, high blood creatinine phosphokinase, and hyperlactacidemia.     

Appearance of abnormal electrocorticogram patterns during umbilical cord compression in sheep fetus

A frequent cause of fetal acidemia, which sometimes results in hypoxic-ischemic encephalopathy, is umbilical cord compression associated with uterine contraction. Using a sheep model of fetal acidemia, we examined the changes in electrocorticogram (ECoG), carotid artery blood flow, arterial blood pressure and fetal heart rate during cord compression. A characteristic burst of ECoG spikes emerged during cord compression at fetal arterial pH 7.18 even before the pH went down to severe fetal acidemia (less than 7.10). The administration of a neuromuscular blocking agent to the fetus did not abolish the appearance of the spikes. These results suggest that cord compression may cause abnormal brain excitement even in the absence of severe fetal acidemia and that this abnormal excitement can lead to fetal brain dysfunction, if cord compression is repeated or prolonged.