Ob/ob mice as a model of delayed gastric emptying

Diabetic gastroparesis is a well-recognized delay of gastric emptying in diabetic patients. We assessed the gastric emptying rate in ob/ob mice, a genetic model of obesity and diabetes. The basal gastric emptying rate in 22- to 27-week-old ob/ob mice was significantly lower than that in 10- to 11-week-old ob/ob mice (P<.01). Our results indicate that the ob/ob mice are a useful model not only of glucose intolerance but also of delayed gastric emptying as a diabetic complication.     

Chronic Kidney Disease Japan Cohort (CKD-JAC) study: design and methods

The prevalence and incidence of end-stage renal disease (ESRD) in Japan are the highest and the third highest, respectively, in the world, while the incidence of cardiac death in Japan is the lowest among developed countries. A recent study showed that the prevalence of chronic kidney disease (CKD), defined as an estimated glomerular filtration rate (GFR) of less than 60 mL/min/1.73 m(2), is extremely high in Japan, about 20% of the adult population. However, the risk of ESRD and cardiovascular disease (CVD) in the CKD population has not been determined nationwide. For this observational study, we will establish a Chronic Kidney Disease Japan Cohort (CKD-JAC) by enrolling 3,000 patients with CKD in 17 clinical centers around Japan, which will be used to determine the incidence of ESRD and CVD in Japanese CKD patients. Risk factors associated with the development of CVD will also be examined. Comorbidity of diabetes in CKD patients will be analyzed to determine whether it is a risk for rapid progression of CKD and high incidence of CVD. In addition, we will study whether the burden of CKD decreases the QOL of patients, and increases hospitalization or health resource utilization. Insights from the CKD-JAC study will provide a basis for future interventional trials focused on reducing the burden of ESRD and CVD in patients with CKD in Japan.     

Ozone production by amino acids contributes to killing of bacteria

Reactive oxygen species produced by phagocytosing neutrophils are essential for innate host defense against invading microbes. Previous observations revealed that antibody-catalyzed ozone formation by human neutrophils contributed to the killing of bacteria. In this study, we discovered that 4 amino acids themselves were able to catalyze the production of an oxidant with the chemical signature of ozone from singlet oxygen in the water-oxidation pathway, at comparable level to antibodies. The resultant oxidant with the chemical signature of ozone exhibited significant bactericidal activity in our distinct cell-free system and in human neutrophils. The results also suggest that an oxidant with the chemical signature of ozone produced by neutrophils might potentiate a host defense system, when the host is challenged by high doses of infectious agents. Our findings provide biological insights into the killing of bacteria by neutrophils.     

Nitric oxide system is involved in glomerular hyperfiltration in Japanese normo- and micro-albuminuric patients with type 2 diabetes

Glomerular hyperfiltration plays a pathogenic role in the early stages of diabetic nephropathy. Experimental studies in laboratory animals suggest that nitric oxide (NO) might be involved in the pathogenesis of glomerular hyperfiltration. We performed a cross-sectional study to determine the relationship between diabetic glomerular hyperfiltration and the NO system. Normoalbuminuric (n=41), microalbuminuric (n=25), and macroalbuminuric (n=16) patients with type 2 diabetes were recruited in this study and compared with age-matched 84 non-diabetic control subjects. Creatinine clearance and urinary NO(2)(-)/NO(3)(-) excretion (urinary NOx) were measured, and the expression of endothelial cell nitric oxide synthase (ecNOS) was evaluated in human renal tissues. Glomerular hyperfiltration was present in 19 (37.5%) and nine (36.6%) of normoalbuminuric and microalbuminuric type 2 diabetic patients, respectively. The urinary NOx was significantly higher in normoalbuminuric patients compared with normal subjects. Creatinine clearance correlated significantly with urinary NOx in normoalbuminuric and microalbuminuric patients. Immunohistochemical staining intensities for ecNOS were significantly increased in glomerular endothelial cells of microalbuminuric type 2 diabetic patients as compared with the control subjects. These results suggest that NO may contribute to the pathogenesis of glomerular hyperfiltration in Japanese type 2 diabetic patients.     

Increased sensitivity of insulin-sensitive phosphodiesterase to insulin in fat cells from streptozotocin diabetic rats

The effects of insulin on insulin-sensitive phosphodiesterase were investigated in fat cells from control and streptozotocin diabetic rats. Isolated cells were incubated at 37 C for 10 min, with and without insulin. A crude microsomal fraction prepared by differential centrifugation was assayed for phosphodiesterase activity. The enzyme activities in diabetic rats were higher at 0-1 nM insulin than in control rats. The dose-response curve of insulin was biphasic and of the convex type in both groups. In diabetic rats, the curve shifted to the left, and half-maximal stimulation was obtained at 0.06 nM insulin compared with 0.16 nM insulin in control rats. Kinetic analyses of the enzyme from diabetic rats revealed much the same findings as obtained in the controls. Specific binding of insulin in fat cells from control and diabetic rats was 3% and 4.9%/2 X 10(5) cells, respectively, at 24 C for 60-min incubation. Scatchard analysis indicates that the overall binding affinity in diabetic cells was greater than that in the control cells. These results suggest that the insulin effector system related to phosphodiesterase activation is intact and has an increased sensitivity in fat cells from streptozotocin diabetic rats; there is also a good correlation with alteration of insulin binding to its receptors.     

Somatostatin and insulin secretion from pancreatic islets: studies on the effect of high K+, 9-aminoacridine and valinomycin

We attempted to determine whether a decrease in the potassium permeability of the D cell membrane plays a role in the stimulus-secretion coupling, as it does in the pancreatic B cell. Elevation in the extracellular potassium concentration from 5.5 to 16.5 mM, or 0.2 mM 9-aminoacridine, which decreases potassium permeability in plasma membrane, stimulated the release of somatostatin as well as insulin from the isolated rat pancreatic islets. Valinomycin (1 microM), a potassium ionophore inhibited the secretion in response to high glucose, high extracellular potassium or 9-aminoacridine. These findings indicate that a reduction in potassium permeability in the D cell membrane, as induced by glucose or other stimulants, may be a major step in secretion of somatostatin.     

Reducing False-Positive Biopsies using Deep Neural Networks that Utilize both Local and Global Image Context of Screening Mammograms

Journal of Digital Imaging - Breast cancer is the most common cancer in women, and hundreds of thousands of unnecessary biopsies are done around the world at a tremendous cost. It is crucial to...