Late-onset obesity in mice transgenic for the human renin gene

We previously generated a strain of transgenic mice carrying the human renin gene, hRN8-12, in the background of C57BL/6j. In this study, we discovered that hRN8-12 male mice, but not females, developed obesity starting at 15 weeks of age. The body weight of 60-week-old male transgenic mice was 2 times higher than that of age-matched wild-type mice. Interestingly, male mice heterozygous for the human renin gene showed moderate weight gain compared with transgenic and wild-type mice. Obese hRN8-12 mice exhibited hyperglycemia, hyperinsulinemia, hyperleptinemia, and hyperlipidemia, and increase in weight in the adipose tissue, liver, heart, and kidneys. Histological analysis demonstrated that fatty hRN8-12 mice developed hypertrophy of pancreatic islets and fatty liver. These results suggested that hRN8-12 mice are associated with obesity dependent on the transgene dosage and should be a genetic model for late-onset obesity.     

Functional evaluation of lung by Xe-133 lung ventilation scintigraphy before and after lung volume reduction surgery (LVRS) in patients with pulmonary emphysema

We evaluated the respiratory functions of patients with pulmonary emphysema who underwent lung volume reduction surgery (LVRS) by the mean transit time (MTT) with Xe-133 lung ventilation scintigraphy, forced expiration volume in 1 sec (FEV1.0), residual volume (RV), distance walked in 6 min (6-min walk), and the Hugh-Jones classification (H-J classification) before and after LVRS. In 69 patients with pulmonary emphysema (62 men, 7 women; age range, 47-75 years; mean age, 65.4 years +/- 6.1, preoperative H-J classification, III (two were II)-V) who underwent LVRS, all preoperative and postoperative parameters (MTT 3 weeks after LVRS and the others 3 months after LVRS) were judged statistically by the Wilcoxon signed-ranks test and Odds ratio. Every postoperative parameter was improved with a significant difference (P < 0.05) compared to preoperative parameters. MTT at 3 weeks after LVRS was not associated with %FEV1.0 and the H-J classification at 3 months after LVRS, but was associated with RV and a 6-min walk at 3 months after LVRS. MTT was useful for the clinical evalution of aerobic capability after LVRS.     

Flavonoids such as luteolin, fisetin and apigenin are inhibitors of interleukin-4 and interleukin-13 production by activated human basophils

BACKGROUND: We have previously shown that fisetin, a flavonol, inhibits IL-4 and IL-13 synthesis by allergen- or anti-IgE-antibody-stimulated basophils. This time, we investigated the inhibition of IL-4 and IL-13 production by basophils by other flavonoids and attempted to determine the fundamental structure of flavonoids related to inhibition. We additionally investigated whether flavonoids suppress leukotriene C4 synthesis by basophils and IL-4 synthesis by T cells in response to anti-CD3 antibody. METHODS: Highly purified peripheral basophils were stimulated for 12 h with anti-IgE antibody alone or anti-IgE antibody plus IL-3 in the presence of various concentrations of 18 different kinds of flavones and flavonols. IL-4 and IL-13 concentrations in the supernatants were then measured. Leukotriene C4 synthesis was also measured after basophils were stimulated for 1 h in the presence of flavonoids. Regarding the inhibitory activity of flavonoids on IL-4 synthesis by T cells, peripheral blood mononuclear cells were cultured with flavonoids in anti-CD3-antibody-bound plates for 2 days. RESULTS: Luteolin, fisetin and apigenin were found to be the strongest inhibitors of both IL-4 and IL-13 production by basophils but did not affect leukotriene C4 synthesis. At higher concentrations, these flavonoids suppressed IL-4 production by T cells. Based on a hierarchy of inhibitory activity, the basic structure for IL-4 inhibition by basophils was determined. CONCLUSIONS: Due to the inhibitory activity of flavonoids on IL-4 and IL-13 synthesis, it can be expected that the intake of flavonoids, depending on the quantity and quality, may ameliorate allergic symptoms or prevent the onset of allergic diseases.     

Dielectric behavior of pulmonary edema induced in the rat lung

The dielectric properties (conductivity, kappa and relative permittivity, epsilon) of excised rat lung are modified by lung air and water content. The measurements of these quantities were made over the frequency range of 10 kHz to 100 MHz with an open-ended coaxial probe. The following relationships were analyzed in an oleic acid-induced pulmonary edema model using 18 animals: the spectra of kappa, epsilon and the loss tangent as a function of lung air and water content. Secondly, an isolated-perfused lung system was produced to induce a gradual increase in lung water. The time course of kappa, epsilon and the loss tangent for one excised lung was analyzed. The principal findings were: (i) a decrease in kappa and epsilon with increasing air content, (ii) an increase in kappa and epsilon with increasing water content, and (iii) a good correlation between lung water content and maximum loss tangent that was insensitive to changes in air content. We conclude that this technique could provide a quantitative assessment of lung water during pulmonary edema formation.     

Chronologic changes of activities of naphthol AS-D acetate esterase and other nonspecific esterases in the mononuclear phagocytes of tuberculous lesions.

Nonspecific esterases of mononuclear phagocytes (MNs) were studied histochemically in the developing and healing tuberculous lesions produced in rabbit skin by bacille Calmette Guérin (BCG). Nonspecific esterases were assayed with the following substrates: naphthol AS-D acetate (AS-D), naphthol AS-D chloroacetate (AS-D Chl), naphthol AS acetate (AS) and alpha-naphthyl acetate (alpha-N), beta-Galactosidase, a lysosomal enzyme of MNs, was also assayed as a marker of MN activation. The number of MNs hydrolyzing AS-D Chl, AS, and alpha-N increased for 2 to 4 weeks after infection. These chronologic changes were similar to that of beta-galactosidase. In contrast, MNs hydrolyzing AS-D appeared predominantly in the healing lesions five to six weeks after infection. These MNs had the morphologic features of balloon-like cells. They contained few lysosomes and gathered in clumps far from the caseous center. The activity of the AS-D esterase was almost completely inhibited by various trypsin inhibitors, but not by the serine esterase inhibitor of phenylmethylsulfonyl-fluoride. These results suggest that the AS-D esterase is a trypsin-like esterase which participates in the healing of tuberculous lesions.     

A single-strip mini-paper chromatographic method for rapid purity-control of 99mTc-labeled radiopharmaceuticals

A single-strip miniaturized paper chromatographic method (Mini-PC) was developed using 80%-90% acetone solvent for rapid purity-control of 99mTc-radiopharmaceuticals. Routine 99mTc-radiopharmaceuticals (eight kinds of "kit" made agents) and diluted agents (in which radiochemical impurities might be formed) were analyzed by Mini-PC and other methods. This showed that, compared with the other methods, the Mini-PC technique is useful for the simple and rapid routine analysis of radiochemical impurities of "kit" made 99mTc-radiopharmaceuticals.     

A Pilon Fracture With Fibular Head Dislocation Treated With the Use of 3D Preoperative Planning: A Case Report and Literature Review

Pilon fractures with intact fibula have been associated with low-energy trauma. However, the compression force onto the ankle joint can damage the tibiofibular linkage as in a Maisonneuve fracture. Herein, we describe a case of a patient who had a pilon fracture (AO type 43 C3.2) without a fibular fracture. Three-dimensional preoperative simulation by reduction with the surface registration technique was performed as the fibular length was intact and there was no reference for the tibial length. The preoperative simulation revealed superior fibular head dislocation and shortening of the distal tibia. After emergency external fixation on the day of arrival, a 2-staged surgery was performed. During the first operation, the fibular head was reduced and the tibial posterolateral fragment was fixed to restore the tibia length. During the second operation, medial and anterolateral fragments were fixed in order to reduce joint surface of the distal tibia. In general, proximal fibular head fractures are easily overlooked. In the case of pilon fractures with severe length shortening of the tibia without a fibular fracture, a proximal tibiofibular injury should be suspected.     

All-case Japanese post-marketing surveillance of the real-world safety and efficacy of rituximab treatment in patients with refractory nephrotic syndrome

Clinical and Experimental Nephrology - Rituximab is conditionally approved in Japan for use in patients with refractory nephrotic syndrome. To meet the conditions of approval, an all-case...