Strain difference in transgene-induced tumorigenesis and suppressive effect of ionizing radiation

Transgenic expression in medaka of the Xiphophorus oncogene xmrk, under a pigment cell specific mitf promoter, induces hyperpigmentation and pigment cell tumors. In this study, we crossed the Hd-rR and HNI inbred strains because complete genome information is readily available for molecular and genetic analysis. We prepared an Hd-rR (p53^+/−, p53^−/−) and Hd-rR HNI hybrid (p53^+/−) fish-based xmrk model system to study the progression of pigment cells from hyperpigmentation to malignant tumors on different genetic backgrounds. In all strains examined, most of the initial hyperpigmentation occurred in the posterior region. On the Hd-rR background, mitf:xmrk-induced tumorigenesis was less frequent in p53^+/− fish than in p53^−/− fish. The incidence of hyperpigmentation was more frequent in Hd-rR/HNI hybrids than in Hd-rR homozygotes; however, the frequency of malignant tumors was low, which suggested the presence of a tumor suppressor in HNI genetic background fish. The effects on tumorigenesis in xmrk-transgenic immature medaka of a single 1.3 Gy irradiation was assessed by quantifying tumor progression over 4 consecutive months. The results demonstrate that irradiation has a different level of suppressive effect on the frequency of hyperpigmentation in purebred Hd-rR compared with hybrids.     

Middle-preserving pancreatectomy with reversed pancreaticogastrostomy: report of a case

Parenchyma-sparing pancreatic resections have been reported increasingly in recent years; however, for multifocal diseases involving the head and the tail of the pancreas, total pancreatectomy is still the preferred procedure. The possible consequence of this procedure is loss of normal pancreatic parenchyma, resulting in insufficiency of pancreatic exocrine and endocrine functions. Various types of limited resection have been introduced for isolated or multiple pancreatic lesions, depending on the location of the tumor. Even for multifocal diseases, if the pancreatic body is spared, a middle-preserving pancreatectomy (MPP) can be performed to assure maximal pancreatic function and uncompromised quality of life. Yet, few papers have introduced the feasibility of MPP for a better outcome. This report describes a new surgical technique for MPP using an alternative approach for the remnant pancreas anastomosis. We used this technique successfully to remove a bifocal neoplasm: adenocarcinoma of the distal bile duct and mucinous cyst adenoma in the tail of the pancreas.     

Improved quantification of amyloid burden and associated biomarker cut-off points: results from the first amyloid Singaporean cohort with overlapping cerebrovascular disease

European Journal of Nuclear Medicine and Molecular Imaging - The analysis of the [11C]PiB-PET amyloid images of a unique Asian cohort of 186 participants featuring overlapping vascular diseases...     

Cushing Syndrome

Cushing syndrome is the constellation of signs and symptoms caused by protracted exposure to glucocorticoids. The most common cause of Cushing syndrome in children and adolescents is exogenous administration of glucocorticoids. Presenting features commonly include weight gain, growth retardation, hirsutism, obesity, striae, acne and hypertension. Almost invariably, linear growth is severely diminished, a factor which may be useful in differentiating between childhood obesity and Cushing syndrome. Diagnostic approaches are based on distinguishing between adrenocorticotropic hormone (ACTH)-dependent and ACTH-independent etiologies, and consideration of the most likely diagnosis by age. Treatment modality is dependent upon etiology. After cure, important components of care include attention to linear growth, pubertal progression and body composition.     

Inactive conformation of the serpin alpha(1)-antichymotrypsin indicates two-stage insertion of the reactive loop: implications for inhibitory function and conformational disease

The serpins are a family of proteinase inhibitors that play a central role in the control of proteolytic cascades. Their inhibitory mechanism depends on the intramolecular insertion of the reactive loop into beta-sheet A after cleavage by the target proteinase. Point mutations within the protein can allow aberrant conformational transitions characterized by beta-strand exchange between the reactive loop of one molecule and beta-sheet A of another. These loop-sheet polymers result in diseases as varied as cirrhosis, emphysema, angio-oedema, and thrombosis, and we recently have shown that they underlie an early-onset dementia. We report here the biochemical characteristics and crystal structure of a naturally occurring variant (Leu-55-Pro) of the plasma serpin alpha(1)-antichymotrypsin trapped as an inactive intermediate. The structure demonstrates a serpin configuration with partial insertion of the reactive loop into beta-sheet A. The lower part of the sheet is filled by the last turn of F-helix and the loop that links it to s3A. This conformation matches that of proposed intermediates on the pathway to complex and polymer formation in the serpins. In particular, this intermediate, along with the latent and polymerized conformations, explains the loss of activity of plasma alpha(1)-antichymotrypsin associated with chronic obstructive pulmonary disease in patients with the Leu-55-Pro mutation.     

Development of hydroxyapatite-ciprofloxacin bone-implants using "Quality by design"

The present study deals with the development of hydroxyapatite (HAp)-ciprofloxacin bone-implants using the ?Quality by design? approach. The effect of various synthesis parameters like drug amount added in the process, stirring speed and addition rate of orthophosphoric acid in the synthesis on drug concentration in the HAp-ciprofloxacin system synthesized by the precipitation technique using 23 factorial design was analyzed. Optimization methodology utillizing the first-order polynomial equation was used to search for optimal drug concentration in the HAp-ciprofloxacin implant system. The observed responses coincided well with the predicted values from the optimization technique. New implants were manufactured using various HAp-ciprofloxacin composites and 1.5 % (m/V) guar gum as a binder. Characterization of the delivery system was done by XRPD, FTIR spectroscopy and SEM. Even at highest drug concentration (76.6 ± 0.5 %, m/m), ciprofloxacin was present in noncrystalline state. The in vitro ciprofloxacin release from various bone-implants was sustained for several weeks and the drug release pattern correlated well with the Korsmeyer- Peppas model.