Nitric oxide promotes the progression of periapical lesion via inducing macrophage and osteoblast apoptosis

This study aimed to elucidate the modulation by nitric oxide (NO) of the apoptosis of macrophages and osteoblasts, the essential cellular components in the development of periapical lesions. Lipopolysaccharide (LPS) induced prominent nitrite synthesis in J774 mouse macrophage cell lines. Exposure to LPS induced obvious apoptosis in J774 cells, whereas transient transfection with murine inducible nitric oxide synthase (iNOS), small interfering RNA (siRNA) diminished this effect. Tumor necrosis factor-alpha (TNF-alpha) and S-nitroso-N-acetyl-DL-penicillamine (SNAP) (a NO donor) triggered apoptosis in UMR-106 rat osteoblastic cell lines and a synergistic effect was noted when TNF-alpha and SNAP were added to the medium together. Administration of siRNAs for c-Fos and c-Jun: components of activator protein-1 (AP-1) and transforming growth factor-beta1 attenuated the combined effect markedly. Terminal deoxynucleotidyl transferase-mediated nick end-labeling (TUNEL) stain in a rat model of induced periapical lesion showed positive apoptotic signals in macrophages and osteoblasts. Administration of N(G)-monomethyl-l-arginine markedly diminished the extent of bone loss and the amounts of apoptotic macrophages and osteoblasts. In conclusion, NO mediates LPS-stimulated apoptosis of macrophages. It also induces osteoblast apoptosis and augments the pro-apoptotic effect of cytokines. Inhibition of NO synthesis in vivo attenuates apoptosis and the size of periapical lesions. Taken together, these results suggest that NO may promote the progression of periapical lesion by inducing the apoptosis of macrophages and osteoblasts.     

Microalbuminuria and the metabolic syndrome and its components in the Chinese population

BACKGROUND: Microalbuminuria and the metabolic syndrome (MetS) have both been linked to chronic kidney disease and cardiovascular disease. This study investigated the association between urinary albumin-to-creatinine ratio (ACR) and MetS and its components. MATERIALS AND METHODS: A total of 2311 subjects aged 40 years and over were recruited in 2004 in a metropolitan city in Taiwan. The biochemical indices, such as fasting glucose levels, urinary albumin, urinary creatinine and anthropometric indices, were measured. We defined microalbuminuria as a urinary ACR ranging from 30 to 300 mg g(-1) creatinine. MetS was defined using the American Heart Association and the National Heart, Lung and Blood Institute (AHA/NHLBI) and the International Diabetes Federation (IDF) definitions. The relationship between MetS and microalbuminuria was examined using multiple logistical regression analysis. RESULTS: Subjects with microalbuminuria had higher age, body mass index (BMI), waist circumference, blood pressure, fasting plasma glucose, triglycerides, total cholesterol (TCHOL)/high-density lipoprotein cholesterol (HDL-C) ratio, prevalence of diabetes mellitus and hypertension and lower HDL-C than subjects with normoalbuminuria. After adjusting for age and BMI, microalbuminuria was associated with the individual components of MetS, except in central obesity in women and elevated fasting glucose in men. After adjusting for age, BMI, smoking and alcohol consumption status, multiple logistical regressions revealed that microalbuminuria is strongly associated with MetS in both genders and according to both definitions. The odds ratio of having MetS using the AHA/NHLBI and IDF definition was 1.76 (1.16-2.67) and 1.73 (1.06-2.83) in men and 2.19 (1.38-3.50) and 2.09 (1.24-3.51) in women, respectively. CONCLUSIONS: Microalbuminuria was strongly associated with MetS and its components. There is an increased likelihood of having MetS if subjects have microalbuminuria.     

Alberta infant motor scale: reliability and validity when used on preterm infants in Taiwan

BACKGROUND AND PURPOSE: The goal of this study was to examine the reliability and validity of measurements obtained with the Alberta Infant Motor Scale (AIMS) for evaluation of preterm infants in Taiwan. SUBJECTS: Two independent groups of preterm infants were used to investigate the reliability (n=45) and validity (n=41) for the AIMS. METHODS: In the reliability study, the AIMS was administered to the infants by a physical therapist, and infant performance was videotaped. The performance was then rescored by the same therapist and by 2 other therapists to examine the intrarater and interrater reliability. In the validity study, the AIMS and the Bayley Motor Scale were administered to the infants at 6 and 12 months of age to examine criterion-related validity. RESULTS: Intraclass correlation coefficients (ICCs) for intrarater and interrater reliability of measurements obtained with the AIMS were high (ICC=.97-.99). The AIMS scores correlated with the Bayley Motor Scale scores at 6 and 12 months (r=.78 and.90), although the AIMS scores at 6 months were only moderately predictive of the motor function at 12 months (r=.56). CONCLUSION AND DISCUSSION: The results suggest that measurements obtained with the AIMS have acceptable reliability and concurrent validity but limited predictive value for evaluating preterm Taiwanese infants.     

Genomic Profiling of Intrahepatic Cholangiocarcinoma: Refining Prognosis and Identifying Therapeutic Targets

Background

The molecular alterations that drive tumorigenesis in intrahepatic cholangiocarcinoma (ICC) remain poorly defined. We sought to determine the incidence and prognostic significance of mutations associated with ICC among patients undergoing surgical resection.

Methods

Multiplexed mutational profiling was performed using nucleic acids that were extracted from 200 resected ICC tumor specimens from 7 centers. The frequency of mutations was ascertained and the effect on outcome was determined.

Results

The majority of patients (61.5 %) had no genetic mutation identified. Among the 77 patients (38.5 %) with a genetic mutation, only a small number of gene mutations were identified with a frequency of >5 %: IDH1 (15.5 %) and KRAS (8.6 %). Other genetic mutations were identified in very low frequency: BRAF (4.9 %), IDH2 (4.5 %), PIK3CA (4.3 %), NRAS (3.1 %), TP53 (2.5 %), MAP2K1 (1.9 %), CTNNB1 (0.6 %), and PTEN (0.6 %). Among patients with an IDH1-mutant tumor, approximately 7 % were associated with a concurrent PIK3CA gene mutation or a mutation in MAP2K1 (4 %). No concurrent mutations in IDH1 and KRAS were noted. Compared with ICC tumors that had no identified mutation, IDH1-mutant tumors were more often bilateral (odds ratio 2.75), while KRAS-mutant tumors were more likely to be associated with R1 margin (odds ratio 6.51) (both P < 0.05). Although clinicopathological features such as tumor number and nodal status were associated with survival, no specific mutation was associated with prognosis.

Conclusions

Most somatic mutations in resected ICC tissue are found at low frequency, supporting a need for broad-based mutational profiling in these patients. IDH1 and KRAS were the most common mutations noted. Although certain mutations were associated with ICC clinicopathological features, mutational status did not seemingly affect long-term prognosis.     

Holomorphic curves in surfaces of general type

This note answers some questions on holomorphic curves and their distribution in an algebraic surface of positive index. More specifically, we exploit the existence of natural negatively curved "pseudo-Finsler" metrics on a surface S of general type whose Chern numbers satisfy c(2)1>2c2 to show that a holomorphic map of a Riemann surface to S whose image is not in any rational or elliptic curve must satisfy a distance decreasing property with respect to these metrics. We show as a consequence that such a map extends over isolated punctures. So assuming that the Riemann surface is obtained from a compact one of genus q by removing a finite number of points, then the map is actually algebraic and defines a compact holomorphic curve in S. Furthermore, the degree of the curve with respect to a fixed polarization is shown to be bounded above by a multiple of q - 1 irrespective of the map.     

Criterion for biholomorphic equivalence of isolated hypersurface singularities

Two germs of complex analytic hypersurfaces with isolated singularities are biholomorphically equivalent if and only if they have the same dimension and their moduli algebras are isomorphic.     

Autologous stem cell transplantation using modified TAM or combination of triple-alkylating agents conditioning regimens as one of the post-remission treatments in patients with adult acute myeloid leukemia in first complete remission

A total of 174 newly diagnosed adult acute myeloid leukaemia (AML) patients were treated in first complete remission (CR1) using modified TAM or a combination of triple-alkylating agents followed by autologous transplantation (AT). Cytogenetic risk groups were classified and most patients received mobilized peripheral blood stem/progenitor cells (PBSCs). The infused cell dose consisted of a median of 4.1+/-2 (range, 1.2-17.1)x 10(6)/kg CD34+ cells. With a median follow-up of 51 months (range, 5-131 months) after CR1, the estimated 5-year disease-free survival (DFS) rate was 68 (95% confidence interval (CI), 63-73%) and the event-free survival rate at 5 years was 59 (95% CI, 54-64%). AML patients other than M3 subtype, the long-term DFS rate was 76, 33% for favourable and unfavourable risk groups, respectively. In all, 40 patients had relapses (40/174, 23%) at the median 15 months after CR1 (range, 8-66 months). Overall, seven patients (4%) died in connection with AT. The infused CD34+ cell dose (P=0.0389) was associated with survival by multivariate analysis. In conclusion, two novel conditioning regimens in AT are feasible for adults with variable risk AML followed for over a 10-year period.