Relative frequency of underlying genetic causes for the development of UPD(14)pat-like phenotype

Paternal uniparental disomy 14 (UPD(14)pat) results in a unique constellation of clinical features, and a similar phenotypic constellation is also caused by microdeletions involving the DLK1-MEG3 intergenic differentially methylated region (IG-DMR) and/or the MEG3-DMR and by epimutations (hypermethylations) affecting the DMRs. However, relative frequency of such underlying genetic causes remains to be clarified, as well as that of underlying mechanisms of UPD(14)pat, that is, trisomy rescue (TR), gamete complementation (GC), monosomy rescue (MR), and post-fertilization mitotic error (PE). To examine this matter, we sequentially performed methylation analysis, microsatellite analysis, fluorescence in situ hybridization, and array-based comparative genomic hybridization in 26 patients with UPD(14)pat-like phenotype. Consequently, we identified UPD(14)pat in 17 patients (65.4%), microdeletions of different patterns in 5 patients (19.2%), and epimutations in 4 patients (15.4%). Furthermore, UPD(14)pat was found to be generated through TR or GC in 5 patients (29.4%), MR or PE in 11 patients (64.7%), and PE in 1 patient (5.9%). Advanced maternal age at childbirth (≥35 years) was predominantly observed in the MR/PE subtype. The results imply that the relative frequency of underlying genetic causes for the development of UPD(14)pat-like phenotype is different from that of other imprinting disorders, and that advanced maternal age at childbirth as a predisposing factor for the generation of nullisomic oocytes through non-disjunction at meiosis 1 may be involved in the development of MR-mediated UPD(14)pat.     

Safety of high doses of Propionibacterium freudenreichii ET-3 culture in healthy adult subjects

Propionibacterium freudenreichii ET-3 (7025) culture, a cell-free product of whey fermentation by P. freudenreichii ET-3, has been shown to promote the growth of Bifidobacteria through the action of 1,4-dihydroxy-2-naphthoic acid (DHNA). Here we report the results of two clinical studies designed to evaluate the safety of high doses of P. freudenreichii ET-3 culture medium. Study 1 had a randomized, double-blind, crossover design. Ten healthy male and four healthy female subjects received 45 tablets of either P. freudenreichii ET-3 culture medium (total daily intake of 3g solid content and 283.5μg of DHNA; active group) or placebo (unfermented product) during two 1-week supplementation periods separated by a 4-week washout period. In Study 2, 11 healthy men took four tablets of P. freudenreichii ET-3 culture medium per day (total daily intake of 0.267g solid content and 22.5μg of DHNA) for a period of 13weeks. In both studies, hematological, clinical chemistry, and urinary parameters were measured before and after each supplementation period and gastrointestinal symptoms were assessed by questionnaire. In Study 1, there were no statistically significant differences between placebo and active supplementation periods in any measured parameter and the incidence of gastrointestinal symptoms were similar between groups. In Study 2, total protein, white blood cell count, hemoglobin, and mean corpuscular hemoglobin concentration decreased significantly from baseline and mean corpuscular volume and urine pH increased from baseline. The changes in hematological parameters were deemed not to be due to P. freudenreichii ET-3 culture medium supplementation given that all parameters remained within normal ranges and were not consistent with any clinically meaningful effect.     

Factors associated with glycemic control and diabetes self-care among outpatients with schizophrenia and type 2 diabetes

We investigated the influence of the severity of schizophrenia on diabetes self-care and glycemic control among outpatients with schizophrenia and diabetes. We conducted interviews with 38 participants and reviewed their clinical charts. The mean hemoglobin A1c (HbA1c) level in the full study population was 7.65%. There was no difference in the HbA1c level between two groups of subjects classified by the severity of schizophrenia. Some diabetes self-care indicators were significantly lower in patients with high Brief Psychiatric Rating Scale scores (P < .05). Although psychotic symptoms do not appear to affect glycemic control, psychotic symptoms might affect diabetes self-care behaviors in people with schizophrenia.     

Usefulness of lipoprotein ratios in assessing carotid atherosclerosis in Japanese type 2 diabetic patients

ObjectiveIt is indicated that total/HDL cholesterol and LDL/HDL cholesterol ratios have more predictive power for cardiovascular disease compared to classic lipid parameters. However, there have been few reports about the usefulness of these indices for the assessment of early stage atherosclerosis in Japanese type 2 diabetic subjects.MethodsWe examined the relation between various lipid parameters and carotid atherosclerosis in 934 type 2 diabetic subjects without apparent atherosclerotic diseases (males, 71.7%; age, 59.6 ± 10.5 years (mean ± SD)). Serum concentrations of total cholesterol (TC), HDL cholesterol (HDL-C), and triglyceride were measured. LDL cholesterol (LDL-C) level was calculated using the Friedewald formula. The presence of carotid plaque and intima-media thickness (IMT) were evaluated by ultrasonography.ResultsA stepwise multivariate regression analysis demonstrated that HDL-C (β = ?0.110, p < 0.001), TC/HDL-C (β = 0.132, p < 0.001) and LDL-C/HDL-C ratios (β = 0.132, p < 0.001) were independent determinants of IMT even after adjustment of other conventional risk factors. However, there was no significant correlation between IMT and TC, triglyceride, LDL-C, and non-HDL-C levels. TC/HDL-C and LDL-C/HDL-C ratios and non-HDL-C levels were significantly higher, but HDL-C levels were significantly lower in patients with carotid plaque than those without it (p < 0.05). There was no significant difference between the groups regarding TC, LDL-C, and triglyceride levels. Furthermore, TC/HDL-C (OR; 1.34, p < 0.001) and LDL-C/HDL-C (OR; 1.54, p < 0.001) ratios showed a positive and linear relationship with the prevalence of carotid plaque, whether covariates were adjusted or not.ConclusionsTC/HDL-C and LDL-C/HDL-C ratios are useful as a tool to assess the risk of early stage atherosclerosis in Japanese type 2 diabetic patients.     

Lotus japonicus nodulation is photomorphogenetically controlled by sensing the red/far red (R/FR) ratio through jasmonic acid (JA) signaling

Light is critical for supplying carbon to the energetically expensive, nitrogen-fixing symbiosis between legumes and rhizobia. Here, we show that phytochrome B (phyB) is part of the monitoring system to detect suboptimal light conditions, which normally suppress Lotus japonicus nodule development after Mesorhizobium loti inoculation. We found that the number of nodules produced by L. japonicus phyB mutants is significantly reduced compared with the number produced of WT Miyakojima MG20. To explore causes other than photoassimilate production, the possibility that local control by the root genotype occurred was investigated by grafting experiments. The results showed that the shoot and not the root genotype is responsible for root nodule formation. To explore systemic control mechanisms exclusive of photoassimilation, we moved WT MG20 plants from white light to conditions that differed in their ratios of low or high red/far red (R/FR) light. In low R/FR light, the number of MG20 root nodules dramatically decreased compared with plants grown in high R/FR, although photoassimilate content was higher for plants grown under low R/FR. Also, the expression of jasmonic acid (JA) -responsive genes decreased in both low R/FR light-grown WT and white light-grown phyB mutant plants, and it correlated with decreased jasmonoyl-isoleucine content in the phyB mutant. Moreover, both infection thread formation and root nodule formation were positively influenced by JA treatment of WT plants grown in low R/FR light and white light-grown phyB mutants. Together, these results indicate that root nodule formation is photomorphogenetically controlled by sensing the R/FR ratio through JA signaling.     

Loss of ABCB7 gene: pathogenesis of mitochondrial iron accumulation in erythroblasts in refractory anemia with ringed sideroblast with isodicentric (X)(q13)

An isodicentric (X)(q13) (idicXq13) is a rare, acquired chromosomal abnormality originated by deletion of the long arm from Xq13 (Xq13-qter), and is found in female patients with hematological disorders involving increased ringed sideroblasts (RSs), which are characterized by mitochondrial iron accumulation around the erythroblast nucleus. The cause of increased RSs in idicXq13 patients is not fully understood. Here, we report the case of a 66-year-old female presenting with refractory anemia with ringed sideroblasts (RARS), and idicXq13 on G-banded analysis. We identify the loss of the ABCB7 (ATP-binding cassette subfamily B member-7) gene, which is located on Xq13 and is involved in mitochondrial iron transport to the cytosol, by fluorescent in situ hybridization (FISH) analysis and the decreased expression level of ABCB7 mRNA in the patient's bone marrow cells. Further FISH analyses showed that the ABCB7 gene is lost only on the active X-chromosome, not on the inactive one. We suggest that loss of ABCB7 due to deletion of Xq13-qter at idicXq13 formation may have contributed to the increased RSs in this patient. These findings suggest that loss of the ABCB7 gene may be a pathogenetic factor underlying mitochondrial iron accumulation in RARS patients with idicXq13.     

Phase II study of amrubicin in previously untreated patients with extensive-disease small cell lung cancer: West Japan Thoracic Oncology Group (WJTOG) study

Summary Purpose: To evaluate the efficacy and safety of amrubicin, (+)-(7S, 9S)-9-acetyl-9-amino-7-[(2-deoxy-β-D-erythro-pentopyranosyl )oxy ]-7,8,9,10-tetrahydro-6,11-dihydroxy-5,12-naphthacenedione hydrochloride, in previously untreated patients with extensive-disease small cell lung cancer (SCLC). Patients and methods: A total of 35 previously untreated patients with extensive-disease SCLC were entered into the study. Amrubicin was given by daily intravenous infusion at 45 mg/m²/day for 3 consecutive days, every 3 weeks. Unless there was tumor regression of 25% or greater after the first cycle, or 50% or greater after the second cycle, treatment was switched to salvage chemotherapy in combination with etoposide (100 mg/m², days 1, 2, and 3) and cisplatin (80 mg/m², day 1). Results: Of the 35 patients entered, 33 were eligible and assessable for efficacy and toxicity. Of the 33 patients, 3 (9.1%) had a complete response (95% confidence interval [CI], 1.9–24.3%) and 22 had a partial response, for an overall response rate of 75.8% (95% CI, 57.7–88.9%). Median survival time was 11.7 months (95% CI, 9.9–15.3 months), and 1-year and 2-year survival rates were 48.5% and 20.2%, respectively. The most common toxicity was hematologic. Non-hematologic toxicity of grade 3 or 4 was only seen in 3 patients with anorexia (9.1%) and 1 patient with alopecia (3.0%). Salvage chemotherapy was administered to only 6 patients. Conclusion: Amrubicin was active for extensive-disease SCLC with acceptable toxicity. Further studies in combination with other agents for SCLC are warranted.     

Use of landiolol hydrochloride for the prevention of atrial fibrillation after lung resection

BACKGROUND: We examined the effect of landiolol hydrochloride, a selective beta1-adrenoreceptor antagonist, on the incidence of atrial fibrillation(AF). METHODS: The incidence of AF after lung resection was evaluated retrospectively in patients with intraoperative treatment with landiolol hydrochloride or those without it. Landiolol hydrochloride (5 microg x kg(-1) x min(-1)) was administered intravenously from the beginning of anesthesia induction to the end of operation. RESULTS: In non-treatment group with landiolol hydrochloride (224 patients), the incidence of AF after surgery was 14.2%, peaking on postoperative day 2, and the average peak day was day 3.5. Older age, removal of the lymph nodes, lengthy surgery, and ischemic heart failure were risk factors. In treatment group with landiolol hydrochloride (77 patients), the incidence of AF after surgery was 5.2%, which was significantly lower than that in non-treatment group. Increased numbers of risk factors led to the high incidence of AF. But the administration of landiolol hydrochloride suppressed the incidence of AF. CONCLUSIONS: Landiolol hydrochloride is effective for the preventionof AF and it is safe without causing a severe decrease in blood pressure and bradycardia in high risk patients.     

Femtosecond pulse laser-oriented recording on dental prostheses: a trial introduction

The purpose of this study was to evaluate the feasibility of using a femtosecond pulse laser processing technique to store information on a dental prosthesis. Commercially pure titanium plates were processed by a femtosecond pulse laser system. The processed surface structure was observed with a reflective illumination microscope, scanning electron microscope, and atomic force microscope. Processed area was an almost conical pit with a clear boundary. When laser pulse energy was 2 microJ, the diameter and depth were approximately 10microm and 0.2 microm respectively--whereby both increased with laser pulse energy. Further, depth of pit increased with laser pulse number without any thermal effect. This study showed that the femtosecond pulse processing system was capable of recording personal identification and optional additional information on a dental prosthesis.