Body odour preferences in men and women: do they aim for specific MHC combinations or simply heterozygosity?

The major histocompatibility complex (MHC) is an immunologically important group of genes that appears to be under natural as well as sexual selection. Several hypotheses suggest that certain MHC-allele combinations (usually heterozygous ones) are superior under selective pressure by pathogens. This could influence mate choice in a way that preferences function to create MHC-heterozygous offspring, or that they function to create specific allele combinations that are beneficial under the current environmental conditions through their complementary or epistatic effects. To test these hypotheses, we asked 121 men and women to score the odours of six T-shirts, worn by two women and four men. Their scorings of pleasantness correlated negatively with the degree of MHC similarity between smeller and T-shirt-wearer in men and women who were not using the contraceptive pill (but not in Pill-users). Depending on the T-shirt-wearer, the amount of variance in the scorings of odour pleasantness that was explained by the degree of MHC similarity (r2) varied between nearly 0 and 23%. There was no apparent effect of gender in this correlation: the highest r2 was actually reached with one of the male odours sniffed by male smellers. Men and women who were reminded of their own mate/ex-mate when sniffing a T-shirt had significantly fewer MHC-alleles in common with this T-shirt-wearer than expected by chance. This suggests that the MHC or linked genes influence human mate choice. We found no significant effect when we tested for an influence of the MHC on odour preferences after the degree of similarity between T-shirt-wearer and smeller was statistically controlled for. This suggests that in our study populations the MHC influences body odour preferences mainly, if not exclusively, by the degree of similarity or dissimilarity. The observed preferences would increase heterozygosity in the progeny. They do not seem to aim for more specific MHC combinations.     

Somatic deletion of the imprinted 11p15 region in sporadic persistent hyperinsulinemic hypoglycemia of infancy is specific of focal adenomatous hyperplasia and endorses partial pancreatectomy

Sporadic persistent hyperinsulinemic hypoglycemia of infancy (PHHI) or nesidioblastosis is a heterogeneous disorder characterized by profound hypoglycemia due to inappropriate hypersecretion of insulin. An important diagnostic goal is to distinguish patients with a focal hyperplasia of islet cells of the pancreas (FoPHHI) from those with a diffuse abnormality of islets (DiPHHI) because management strategies differ significantly. 16 infants with sporadic PHHI resistant to diazoxide and who underwent pancreatectomy were investigated. Selective pancreatic venous sampling coupled with peroperative surgical examination and analysis of extemporaneous frozen sections allowed us to identify 10 cases with FoPHHI and 6 cases with DiPHHI. We show here that in cases of FoPHHI, but not those of DiPHHI, there was specific loss of maternal alleles of the imprinted chromosome region 11p15 in cells of the hyperplastic area of the pancreas but not in normal pancreatic cells. This somatic event is consistent with a proliferative monoclonal lesion. It involves disruption of the balance between monoallelic expression of several maternally and paternally expressed genes. Thus, we provide the first molecular explanation of the heterogeneity of sporadic forms of PHHI such that it is possible to perform only partial pancreatectomy, limited to the focal somatic lesion, so as to avoid iatrogenic diabetes in patients with focal adenomatous hyperplasia.     

Biological evaluation of two anomeric glucose analogues iodinated in position 6

Two anomeric analogues of glucose labelled with 123 iodine in position 6, proposed as tracers of glucose transport in vivo, have been synthesized: alpha- and beta-methyl-6-deoxy-6-iodo-D-glucopyranoside (alpha MDIG and beta MDIG). The aim of this study was to determine whether these molecules interact with the glucose transporter and whether they could be used as tracers of glucose transport in vivo. The biodistribution of alpha MDIG and beta MDIG was studied in the mouse in vivo. To determine if these two anomers enter the cell via the glucose transporter, their uptake was measured in isolated perfused rat hearts, in human erythrocytes in suspension, and in cardiomyocytes of neonatal rat in culture. Both alpha MDIG and beta MDIG had similar repartitions in the mouse: myocardial uptake averaged 7% of the injected dose/g of organ at 2 min postinjection and alpha MDIG competed with D-glucose to enter the cells. Insulin produced a 123% increase of its uptake in isolated perfused rat hearts and a 100% increase in cardiomyocytes of neonatal rat in culture. alpha MDIG uptake was lowered in the presence of glucose transport inhibitors in each experimental model. An interaction between beta MDIG and glucose transporters was observed only in human erythrocytes in suspension. Only alpha MDIG interacts with the glucose transporter, and thus could be used to estimate glucose transport in vivo.     

Cathepsin E expression by normal and premalignant cervical epithelium

We have investigated the expression of the aspartic proteinase cathepsin E and HLA-DR and the presence of HPV16 in normal squamous epithelium (n = 8) and low-grade (n = 21) and high-grade (n = 14) intraepithelial squamous lesions of the uterine cervix. Immunohistochemistry of cervical biopsies revealed that up-regulation of cathepsin E expression was related to increasing severity of the cervical intraepithelial neoplasia (CIN). Up-regulation of protein was associated with increased message as assessed by in situ hybridization. Langerhans cells and the majority of koilocytes did not express detectable cathepsin E levels. Although there was also an up-regulation of HLA-DR expression by cervical keratinocytes in cervical intraepithelial neoplasia lesions, as determined by immunohistochemistry, no significant correlation was found between HLA-DR and cathepsin E expression in these lesions; neither was expression of cathepsin E correlated to the presence of HPV16, detected by polymerase chain reaction. The expression of cathepsin E, an aspartic proteinase that is reported to play a role in antigen processing for presentation by class II major histocompatibility complex molecules, is associated with cellular dedifferentiation in cervical intraepithelial neoplasia.     

The effects of betamethasone derivatives on endotoxin-induced uveitis in guinea pigs

OBJECTIVE AND DESIGN: We reported previously that the betamethasone derivative betamethasone dipropionate behaves as an anti-glucocorticoid in rat endotoxin-induced uveitis (EIU). In the present study, we produced EIU in guinea pigs and investigated the effects of betamethasone dipropionate on the EIU. MATERIAL: Male Hartley guinea pigs were used. TREATMENT: Glucocorticoids were instilled into the eye. METHOD: To elicit EIU, lipopolysaccharide (LPS) was injected into the anterior chamber of the eye. Cell numbers in the aqueous humor after LPS injection were determined by flow cytometry. Prostaglandin E2 (PGE2) production after LPS injection into the anterior chamber was also examined. RESULTS: Intracameral injection of LPS (1 microgram/eye) induced cell infiltration into the anterior chamber and PGE2 production. Betamethasone dipropionate inhibited cell infiltration and PGE2 production more strongly than betamethasone. These results suggest that betamethasone dipropionate is a potent glucocorticoid in guinea pigs. CONCLUSIONS: Structure-activity relationships of glucocorticoids in the guinea pig EIL model may differ from those in the rat EIU model.     

Microflora of periodontal pockets in advanced periodontitis

The aim of study was the evaluation of periodontal pockets microflora in patients with advanced periodontitis. From each subject 16-20 samples were taken using paper points. Pooled sample after 60 s. mixing was serially diluted in reduced BHI. For total cell counts and for the isolation of black pigmented anaerobes Brucella agar supplemented with 5% sheep blood, hemin, menadione, with and without Kanamycin-Vancomycin mixture and BM agar plates were used. For isolation of A. actinomycetemcomitans TSBV agar plates were used. Cultures were incubated in anaerobic chamber at 37 degrees C for 7 days and TSBV agar plates in an atmosphere of 95% air-5% CO2 at 37 degrees C for 5 days. Microorganisms were identified by Gram staining, colony morphology, fluorescence in UV-light, haemagglutination of 3% sheep erythrocytes, fermentation of sugars, production of indole, urease (API 20A), specific enzymes (Rapid ID 32A). Twenty seven subjects with clinically recognized periodontitis were examined. Microorganisms important in periodontitis were isolated from periodontal pockets of almost all examined subjects. The number of bacteria obtained from the sample of one patient ranged from 1 x 10(4) CFU/ml to 3,6 x 10(6) CFU/ml. Porphyromonas gingivalis was identified in the samples taken from 17 patients, Prevotella intermedia-19, Actinobacillus actinomycetemcomitans -11, Fusobacterium nucleatum-9, Peptostreptococcus spp.-22.     

Changes in pain perception and pain-related somatosensory evoked potentials in humans produced by exposure to oscillating magnetic fields

cDNA selection was used to isolate coding sequences from cosmids mapping to the gene-rich telomeric region of human chromosome 21q. A novel cDNA, termed SMT3A, was isolated and mapped between the loci PFKL and D21S171, about 2.2 Mb proximal to the telomere. The predicted protein of 103 amino acids appears to be a homologue of the Saccharomyces cerevisiae SMT3 protein, whose gene was previously isolated as a suppressor of mutations in the MIF2 gene. The yeast MIF2 gene encodes an essential centromeric protein and shows homology to mammalian CENP-C, an integral component of active kinetochores. SMT3A was found to be highly homologous to two other recently isolated human genes, suggesting the presence of a new gene family. Homologous sequences were also found in protozoa, metazoa, and plants. Moreover, all predicted proteins show significant homology to ubiquitin. The proposed role of yeast SMT3 as centromeric protein and the strong evolutionary conservation of the SMT3A gene suggest an involvement of the encoded protein in the function and/or structure of the eukaryotic kinetochore.