Genetic studies of the leptin receptor gene in morbidly obese French Caucasian families

Family studies have shown that in some populations up to 75% of the variation of body mass index can be explained by genetic factors. However, in humans, no major obesity gene has been identified to date. In contrast, there are a number of genetically well defined animal models for obesity. In two of those models (ob/ob and db/db), defects in the same pathway are responsible for obesity. Recently, some evidence has been found for the OB gene also being involved in human obesity. In this study we investigated the potential role of the OB receptor (OBR) in the etiology of massive obesity in humans using familial linkage analyses and case-control association studies. The typing of two microsatellite markers (D1S198 and D1S209), flanking the OBR gene, in 256 sib pairs showed no evidence for linkage with obesity. In order to be able to detect small gene effects, association studies with a 3′-UTR insertion/deletion polymorphism were carried out. The results of these analyses remained non-significant (χ² = 3.442, P = 0.18). However, subjects heterozygous for the insertion/deletion polymorphism showed a slight trend towards lower insulin values 30 min after an oral glucose load compared to homozygous individuals (P = 0.02). In summary, our results do not support a major role of the human OBR gene in the development of morbid obesity in our population. Received: 4 December 1996 / Accepted: 25 June 1997     

Quantitative detection of bisphenol A and bisphenol A diglycidyl ether metabolites in human plasma by liquid chromatography–electrospray mass spectrometry

Due to the ubiquity of epoxy resin compounds and their potential role in increasing the risk for reproductive dysfunction and cancer, the need for an assessment of human exposure is urgent. Therefore, we developed a method for measuring bisphenol A (BPA) and bisphenol A diglycidyl ether (BADGE) metabolites in human blood samples using high-performance liquid chromatography–electrospray ionization mass spectrometry (LC–MS). Human blood samples were processed using enzymatic deconjugation of the glucuronides followed by a novel sample preparation procedure using a solid-phase-cartridge column. This selective analytical method permits rapid detection of the metabolites, free BPA and a hydrolysis product of BADGE (BADGE-4OH) with detection limits in the low nanogram per milliliter range (0.1 ng ml⁻¹ of BPA and 0.5 ng ml⁻¹ of BADGE-4OH). The sample extraction was achieved by Oasis HLB column on gradient elution. The recoveries of BPA and BADGE-4OH added to human plasma samples were above 70.0% with a standard deviation of less than 5.0%. This selective, sensitive and accurate method will assist in elucidating potential associations between human exposure to epoxy-based compounds and adverse health effects.     

Comparison of lethal mutations of Drosophila melanogaster with D. simulans when detected by the attached-X method.

The purpose of this study was to evaluate the attached-X method compared with the standard Basc method, and, using this method, to find out whether the observed differences in genetic polymorphisms are related to differences in lethal mutation rates in D. melanogaster and D. simulans. When EMS-treated Drosophila melanogaster males are mated to untreated attached-X females, a decrease in the progeny sex ratio (male/female + male) is observed due to the induced lethal mutations on the X chromosome. The decrease in the frequency of male progeny were shown as the attached-X index. The expected male number is calculated from the control sex ratio. The difference between the expected and the observed male numbers, expressed as the ratio to the expected male number, defines the attached-X index. The index values for various EMS concentrations were compared to the lethal frequencies obtained by the standard Basc method for the same EMS treatments, and gave a highly positive correlation (gamma = 0.993, p < 0.01, d.f. = 2), thus providing an alternative method for evaluation of possible mutagens. The attached-X method was applied to D. simulans, of which natural populations are known to have relatively low genetic variation, and frequencies of the EMS-induced X chromosome lethal mutations were estimated and compared with those in D. melanogaster. The results indicate that D. melanogaster is slightly more sensitive in the sperm and spermatogonial stages, but less susceptible in the spermatid stage when compared with D. simulans.(ABSTRACT TRUNCATED AT 250 WORDS)     

Congenital diverticulum of the ileum in a rat.

A congenital diverticulum of the ileum (Meckel's diverticulum), approximately 10 mm long, was detected in a rat and examined histologically. The histological findings were basically the same as in the ileum. Although Meckel's diverticulum is uncommon in the rat, the present report demonstrated the possibility of discovering new cases.     

N.m.r. study on the formation and geometry of inclusion complexes of 6-O-(alpha-maltosyl)cyclomalto-hexaose and -heptaose with p-nitrophenol in aqueous solution.

The formation and molecular geometry of inclusion complexes of some branched cyclomaltaoses with p-nitrophenol in aqueous solution have been investigated by using high-resolution 1H-n.m.r. spectroscopy. 6-O-(alpha-Maltosyl)cyclomalto-hexaose and -heptaose were found to form 1:1 inclusion complexes with p-nitrophenol, and the dissociation constants for their complexes are quite similar to those for corresponding unbranched cyclomaltaose-p-nitrophenol complexes, indicating that formation of these inclusion complexes is not hampered by the maltosyl branch. From measurement of nuclear Overhauser enhancements, it was concluded that the maltosyl branch is not situated over the entrance of the cavity.     

Adsorption of mutagens by refined corn bran

Refined corn bran (RCB), a dietary fiber derived from the mechanical refining of corn hulls, effectively adsorbed various environmental mutagens. When RCB was added at a concentration of 10 mg/ml to an aqueous solution of dinitropyrene (DNP), 91.6% of the mutagenicity towards Salmonella tester strain TA98 disappeared. Under similar conditions decreases in mutagenicity of DNP using wheat bran and cellulose powder were 58.4% and 43.0%, respectively. The adsorption of DNP to the fibers appeared irreversible since little mutagenicity was recovered by washing the treated fibers with aqueous buffer solutions of various pHs. Even with an organic solvent (methanol: ammonium hydroxide 50:1), only 2/3 of the mutagenicity of DNP was recovered. RCB could similarly adsorb mutagenic heterocyclic amines such as IQ, Trp-P-1, Trp-P-2, Glu-P-1, and Glu-P-2.