Postoperative changes in mandibular prognathism surgically treated by intraoral vertical ramus osteotomy

This study investigated short- and long-term postoperative skeletal changes following intraoral vertical ramus osteotomy (IVRO) for mandibular prognathism, as determined from lateral cephalograms. The subjects were 20 patients with mandibular prognathism who had undergone surgical orthodontic treatment combined with IVRO. Lateral cephalograms were taken at six time points: 1 month before surgery, and 1 day, 3 months, 6 months, 1 year, and approximately 2 years after surgery. Intermaxillary fixation (IMF) with four monocortical screws was maintained for 1 week in all patients. Mean posterior movement of the menton (Me) was 5.9 mm at surgery. 3 months after surgery, the FMA and FH-CorMe angles had increased 6.3 and 6.2 degrees, respectively, indicating clockwise rotation of the distal segment of the mandible. This rotation was observed in all 20 patients, suggesting that postoperative rotation of the mandible in the postoperative short term is likely to occur after IVRO and could be considered an adaptation of the mastication system newly established by surgery. In the long term after IVRO, Me had moved anteriorly by only 0.9 mm and the relapse ratio was 15.3%. These findings suggest the excellent long-term stability of surgical orthodontic treatment combined with IVRO in patients with mandibular prognathism.     

Whole‐exome sequencing and host cell reactivation assay lead to a diagnosis of xeroderma pigmentosum group D with mild ultraviolet radiation sensitivity

A case of xeroderma pigmentosum (XP) group D in a 39‐year‐old Japanese man is reported. The patient had suffered from moderate to severe solar sensitivity and freckle‐like pigmented macules in sun‐exposed areas since 6 years of age, and developed skin malignancies such as squamous cell carcinoma, actinic keratosis, Bowen’s disease and basal cell carcinoma. The minimal erythema dose for ultraviolet (UV) radiation was decreased with a delayed peak reaction. The level of unscheduled DNA synthesis of fibroblasts from the patient was 70% of normal, while they expressed POLH, a gene product responsible for the XP variant. Whole‐exome sequencing indicated that the patient harbored a homozygous mutation of c.1802G>T, p.Arg601Leu in ERCC2. A genetic complementation test was carried out by host cell reactivation assay, which showed that the patient’s fibroblasts recovered only when they were transfected with XPD cDNA, confirming the diagnosis of XP‐D. Arg601Leu mutation in ERCC2 may be related to mild UV radiation sensitivity and moderate skin lesions.     

Gene Expression Analysis Using a High‐Resolution DNA Microarray of Peripheral Whole Blood Immediately Before and After Leukocytapheresis for Rheumatoid Arthritis

Leukocytapheresis (LCAP) is a safe, unique therapy pertaining to intractable rheumatoid arthritis (RA) even in cases of drug allergy or infectious states. To investigate how to represent LCAP efficacy, we have conducted gene expression analyses from the peripheral blood of RA patients treated with non‐woven polyethylene terephthalate filters. Peripheral blood samples were collected immediately before and after treatment from eight RA patients who received LCAP. Among these patients, all of them achieved 20% improvement in the core set of the American College of Rheumatology (ACR20), and thus, they were confirmed as LCAP responders. Gene expression analysis was done with a high‐resolution DNA microarray. The results of each of the two groups' gene expression values (immediately before and after LCAP) were calculated using Welch's t‐test. Calculations were performed with a statistical software R.basic package: if the P‐value was less than 0.05, this was seen as a significant change. In a comparison of 25 370 gene expressions, the number of genes showing a P‐value < 0.05 in the upregulating group was 2110, and in the downregulating group it was 1864. The results of pathway analysis using the MetaCore program indicate that gene groups work for cytoskeletal remodeling are upregulated, and genes related to immune responses, such as antigens presenting via major histocompatibility complex class I and II, are downregulated just after LCAP. These findings may relate to LCAP efficacy for RA patients, but this needs further investigation.     

Soluble E-selectin, leptin, triglycerides, and insulin resistance in nonobese Japanese type 2 diabetic patients

The aim of the present study was to investigate the relationships between insulin resistance and soluble E-selectin, body mass index (BMI), leptin, and serum lipid profile including triglycerides in nonobese Japanese type 2 diabetic patients. A total of 97 nonobese Japanese type 2 diabetic patients aged 43 to 84 years were examined. The duration of diabetes was 11.2 +/- 0.8 years. In conjunction with BMI and fasting concentrations of plasma glucose, serum lipids (triglycerides, total cholesterol, and high-density lipoprotein cholesterol) and serum insulin, soluble E-selectin, and leptin were also measured. The low-density lipoprotein (LDL) cholesterol level was calculated using the Friedewald formula. Insulin resistance was estimated by the homeostasis model assessment. The subjects were divided into 2 groups according to the value of insulin resistance estimated by the homeostasis model assessment. Values greater than 2.5 were indicative of the insulin-resistant state, and values less than 2.5 were indicative of the insulin-sensitive state. The insulin-resistant group had significantly higher levels of E-selectin, leptin, triglycerides, total and LDL cholesterol, and diastolic blood pressure as compared with the insulin-sensitive group. There was, however, no significant difference in age, sex, diabetes duration, BMI, systolic blood pressure, HbA1c, and high-density lipoprotein cholesterol between the 2 groups. Univariate regression analysis showed that insulin resistance was positively correlated to E-selectin (r = 0.305, P = .003), BMI (r = 0.283, P = .006), leptin (r = 0.296, P = .004), HbA1c (r = 0.241, P = .018), serum triglycerides (r = 0.385, P < .001), serum total (r = 0.240, P = .019) and LDL cholesterol (r = 0.254, P = .013) levels, and systolic (r = 0.247, P = .024) and diastolic (r = 0.305, P = .006) blood pressure. Multiple regression analyses showed that insulin resistance was independently predicted by serum E-selectin (F = 18.4), serum leptin (F = 14.0) and serum triglycerides (F = 20.0) levels, which explained 45.0% of the variability of insulin resistance. From these results, it can be concluded that in conjunction with serum triglycerides and serum leptin, serum E-selectin is another important independent factor associated with insulin resistance in nonobese Japanese type 2 diabetic patients.     

Growth hormone-releasing hormone and gonadotropin-releasing hormone stimulate nitric oxide production in 17beta-estradiol-primed rat anterior pituitary cells

It was reported that neuronal nitric oxide synthase (nNOS) was expressed only in gonadotrophs and folliculo-stellate cells in the anterior lobe of the pituitary gland. However, recent studies have demonstrated the occurrence of nNOS in the somatotrophs and lactotrophs. In the present study, we investigated effects of growth hormone-releasing hormone (GHRH), gonadotropin-releasing hormone (GnRH), and 17β-estradiol on nitric oxide (NO) release in cultured rat anterior pituitary cells in vitro. The NO ₂ ⁻ level in the incubation medium of the rat anterior pituitary cells was dependent on the cell density. Pretreatment with 10 μM 17β-estradiol resulted in an increase in medium NO ₂ ⁻ level. GHRH and GnRH failed to change medium NO ₂ ⁻ levels, but they elicited increases in medium NO ₂ ⁻ levels in estrogen-treated cells. The GHRH-induced increase in NO ₂ ⁻ level was inhibited by Nχ-nitro-l-arginine methyl ester, a NOS inhibitor. These findings suggest that GnRH and GHRH could activate nNOS in the gonadotrophs and the somatotrophs, respectively.     

A case of fulminant type 1 diabetes mellitus with exocrine pancreatic insufficiency and enhanced glucagon response to meal ingestion

Non-specific aggression to endocrine alpha and beta cells as well as exocrine pancreas has been suggested in fulminant type 1 diabetes (FT1DM), while its effect on glucagon secretion and exocrine function is unknown. Here, we report a FT1DM case with exocrine pancreatic insufficiency and enhanced glucagon response to meal ingestion.     

Programmable cells: interfacing natural and engineered gene networks

Novel cellular behaviors and characteristics can be obtained by coupling engineered gene networks to the cell's natural regulatory circuitry through appropriately designed input and output interfaces. Here, we demonstrate how an engineered genetic circuit can be used to construct cells that respond to biological signals in a predetermined and programmable fashion. We employ a modular design strategy to create Escherichia coli strains where a genetic toggle switch is interfaced with: (i) the SOS signaling pathway responding to DNA damage, and (ii) a transgenic quorum sensing signaling pathway from Vibrio fischeri. The genetic toggle switch endows these strains with binary response dynamics and an epigenetic inheritance that supports a persistent phenotypic alteration in response to transient signals. These features are exploited to engineer cells that form biofilms in response to DNA-damaging agents and cells that activate protein synthesis when the cell population reaches a critical density. Our work represents a step toward the development of "plug-and-play" genetic circuitry that can be used to create cells with programmable behaviors.     

Coronary spasm is associated with chronic low-grade inflammation.

BACKGROUND: Coronary spasm plays an important role in the pathogenesis of ischemic heart disease and it may be associated with low-grade inflammation. METHODS AND RESULTS: Intracoronary injection of acetylcholine was done in 199 patients (99 men, 100 women, mean age, 64.5+/-11.0 years) with chest pain and normal coronary angiograms. According to the results of the provocation test, the study subjects were divided into 2 groups: the spasm group of 112 patients and the non-spasm group of 87 patients. Clinical data including high-sensitivity C-reactive protein (hs-CRP) and other coronary risk factors were compared between the 2 groups. Serum levels of hs-CRP were significantly higher in the spasm group than in the non-spasm group (median: 1.2 mg/L vs 0.5 mg/L, p<0.005). Multivariate analysis showed that hs-CRP and smoking history were independently associated with coronary spasm with an odds ratio of 2.28 (p=0.027) and 2.25 (p=0.037), respectively, with a hs-CRP value of > or = 2 mg/L as cutoff point. CONCLUSIONS: Minor elevations of the serum hs-CRP level are significantly associated with coronary spasm, suggesting that chronic low-grade inflammation may be involved in the pathogenesis of coronary spasm.