Variation analysis of β3-adrenergic receptor and melanocortin-4 receptor genes in childhood obesity

BACKGROUND: Decreased energy expenditure and increased food intake are principal causes for obesity. In the present study, genotypes of beta(3)-adrenergic receptor (beta(3)AR) and of melanocortin-4 receptor (MC4R), both of which are believed to have a close link to the cause of obesity, were analyzed and compared with phenotypes of childhood obesity. METHODS: Thirty-five obese children with moderate to severe obesity were enrolled. Direct sequencing of the MC4R coding region and pinpoint-polymerase chain reaction were used to detect genomic variation in the beta(3)AR gene using peripheral blood-derived DNA. RESULTS: Allele frequency of Trp64Arg variation in the beta(3)AR gene in the obese subjects was 0.16, which is comparable with that in the healthy general population in eastern Asia. Comparison of phenotypical characteristics did not show a significant difference between Trp/Trp and Trp/Arg subjects. It was notable that body height SD was significantly higher in the Trp/Trp than the Trp/Arg subjects (0.93 +/- 1.0 SD vs 0.07 +/- 1.3 SD, P= 0.03). Annual weight gains were far beyond a hypothetical fat gain in an Arg64 heterozygote with decreased energy consumption, suggesting increased food intake in childhood obesity. There was, however, no variation in the MC4R gene despite thorough sequencing of the entire coding region. CONCLUSIONS: The Trp64Arg variation in the beta(3)AR gene has no relationship to the degree or the incidence of childhood obesity. The majority of childhood obesity can be characterized as tall stature, more rapid weight gain than that expected by decreased energy expenditure. Further investigation is necessary in regard to the increased food intake as a major cause of childhood obesity.     

Genetic susceptibility to type 2 diabetic nephropathy in human and animal models

SUMMARY:   Diabetic nephropathy is the most common cause of end-stage renal disease (ESRD) in Japan, Western Europe, and the United States. Mega studies such as Diabetes Control and Complication Trial (DCCT), Epidemiology of Diabetes Interventions and Complications (EDIC), and the United Kingdom Prospective Diabetes Study (UKPDS) clarified that poor glycemic and blood pressure control are undoubtedly involved in the development of nephropathy. However, these factors are not sufficient to predict which diabetic patients will develop renal disease, because not all patients with poor glycemic and blood pressure control develop renal disease. Since ethnic variations and familial clustering of diabetic nephropathy have been observed, genetic factors might contribute to susceptibility to this disease. Several methods such as (genome wide) association studies, sib-pair analysis, and quantitative trait loci (QTLs) analysis are available to examine polygenic diseases. However, no mutations that could explain the majority of nephropathy cases have been identified so far. The development of most diabetic nephropathy might be explained by the polygenic effect (i.e. many minor gene-gene interactions might be very important in the development of nephropathy). Identification of candidate genes of nephropathy enables targeting of therapy in patients at risk and development of novel therapeutic agents.     

Ureteral obstruction due to retroperitoneal fibrosis secondary to a solitary internal iliac aneurysm

We report a case of ureteral obstruction due to retroperitoneal fibrosis secondary to a solitary left internal iliac aneurysm. It has been reported that as a cause of ureteral obstruction, an internal iliac aneurysm without aortic and/or common iliac aneurysms is very rare. In the present case, magnetic resonance imaging was a useful modality to diagnose retroperitoneal fibrosis secondary to an internal iliac aneurysm as a direct cause of ureteral obstruction.     

Catheter Ablation of Accessory Atrioventricular Connection between Right Atrial Appendage to Right Ventricle

Accessory AV Connection Between RAA and RV. A 24-year-old woman had experienced frequent attacks of orthodromic AV reciprocating tachycardia. The polarity of the delta waves suggested a right anterior or anterolateral accessory pathway. After ablation at the tricuspid annulus was unsuccessful, earliest retrograde atrial activation was recorded on the floor of the right atrial appendage, 2 cm above the tricuspid ring. Application of radiofrequency en-ergy at this site aholished accessory pathway conduction. This unusual accessory pathway, located between the floor of the right atrial appendage and the right ventricle, was amenable to radiofrequency catheter ablation from within the right atrial appendage.     

Effect of obstructive jaundice on neutrophil chemotactic activity: An in vivo assessment in zymosan-induced peritonitis model in rats

The effect of obstructive jaundice on local neutrophil accumulation in response to inflammatory stimulus was investigated in rats. Obstructive jaundice was produced by bile duct ligation for 7 days. Zymosan (200 mg) was injected intraperitoneally and 4h later myeloperoxidase activity in the peritoneal fluid was measured to quantify neutrophil recruitment. Zymosan-induced neutrophil recruitment was significantly greater (more than two-fold) in bile duct-ligated rats than in sham-ligated or normal animals. Depletion of peritoneal cells significantly suppressed neutrophil recruitment after zymosan injection in all three groups, with no significant differences between the groups. In normal rats, replacement of their peritoneal cells by those from bile duct-ligated rats did not enhance zymosan-induced neutrophil recruitment. In contrast, bile duct-ligated rats treated with peritoneal cell replacement from normals showed significantly increased neutrophil recruitment after zymosan injection. In vitro neutrophil chemotaxis in response to formyl-Met-Leu-Phe was significantly enhanced in bile duct-ligated rats, compared with that in sham-ligated animals. The results suggest that local neutrophil recruitment in response to inflammation may be enhanced in obstructive jaundice and that increased neutrophil chemotactic activity, not macrophage activity, may play a prime role in the mechanism.     

Hepatitis B virus-associated nephropathy: 17 year progression from onset to end-stage renal failure

Hepatitis B virus-associated nephropathy (HB nephropathy) was first described in 1971. There have been few reports on the long-term prognosis in children with HB nephropathy. A case is reported here of a child who presented with symptoms of acute glomerulonephritis at 12 years of age and progressed to end-stage renal failure 17 years after the clinical onset, in spite of the seroconversion of HB virus by formation of HBe antibody.     

Photorejuvenation by Intense Pulsed Light with Objective Measurement of Skin Color in Japanese Patients

BACKGROUND AND OBJECTIVES: This study had two objectives: subjective evaluation of overall skin rejuvenation effects of relatively short-wavelength intense pulsed light (IPL) and objective changes in basic skin tone as measured by a spectrophotometer. STUDY DESIGN/MATERIALS AND METHODS: Twenty-five women selected at random received a series of three IPL treatments. Efficacy was evaluated over a 3-month follow-up period. Concurrently, a spectrophotometer was used to measure "lightness" (L(*)) to quantify the lightening effect changes to pretreatment and posttreatment basic skin tone. RESULTS: Subjective improvement of 50% or more was seen in 18 of 25 patients for pigmentation. One patient showed exacerbation of latent epidermal melasma as a complication. In the spectrophotometric analysis, the mean value of L(*) increased from a baseline value of 60.86 to 63.22, at 3-month follow-up period, with statistical significance. CONCLUSION: IPL skin rejuvenation using relatively shorter wavelengths and pulse widths brought about significant macroscopic and quantitative improvements, especially in the treatment of epidermal pigmentation and improvement of basic skin tone.     

Activation and Inactivation of a Variety of Mutagenic Compounds by the Reconstituted System Containing Highly Purified Preparations of Cytochrome P-450 from Rat Liver

Activation and Inactivation of a Variety of Mutagenic Compoundsby the Reconstituted System Containing Highly Purified Preparationsof Cytochrome P-450 from Rat Liver. KAWANO, S., KAMATAKI, T.,MAEDA, K., KATO, R., NAKAO, T., AND MIZOGUCHI, I. (1985). Fundam.Appl. Toxicol. 5, 487–498. Six cytochrome P-450 preparationsfrom phenobarbital (PB)-treated rats and two preparations fromß-naphthoflavone (BNF)-treated rats were purified.Using Salmonella typhimurium TA98 the ability of these cytochromeP-450 preparations to mutagenically activate and inactivatea variety of carcinogens was examined. High- and low- spin formsof cytochrome P-448 isolated from BNF-treated rats (BNF-IIaand IId) activated various carcinogens. Both forms activated2-aminofluorene, benzo[a]pyrene, and dibenz[a,c]anthracene.However, o-aminoazotoluene and 2-nitrofluorene were activatedonly by the low-spin form, and aflatoxin B1 only by the high-spinform. In contrast, only limited carcinogens were activated bysome preparations from PB-treated rats. 2-Aminofluorene wasactivated by four PB-inducible preparations (PB-Ia, Ic, Id,and IIa), but only moderately. Unexpectedly, however, the mostprominent activation of benzo[a]pyrene was observed with onepreparation (PB-Id) from PB-treated rats. Direct mutagens tothe S. typhimurium, 4-NQO and AF-2, were markedly inactivatedby NADPH-cytochrome c (P-450) reductase without cytochrome P-450,One PB-inducible form (PB-Ic) inactivted 2-nitrofluorene, andthe high- spin form of P-448 (BNF-IIa) inactivated AF-2