In vitro kinetics of two human CYP1A1 variant enzymes suggested to be associated with interindividual differences in cancer susceptibility

A genetic polymorphism (A4889-->G) in the human CYP1A1 gene which creates an Ile462-->Val amino acid substitution has been suggested to cause altered enzymatic properties of CYP1A1. Since several epidemiological studies have shown an association between the CYP1A1-Val allele and lung cancer, we considered it of importance to evaluate the in vitro kinetic properties of the two CYP1A1 variants after expression of each cDNA in yeast. No differences were found in K(m) or Vmax for CYP1A1 dependent O-dealkylation of ethoxyresorufin and 3-hydroxylation of benzo(a)pyrene between the two variants. The data indicate that the Ile/Val polymorphism in human CYP1A1 is not functionally important.     

Cytogenetic abnormalities and clonal evolution in an adult hepatoblastoma

Hepatoblastomas usually occur in children < 3 years of age, and only occasional adult cases have been described. To date, 20 cytogenetically abnormal childhood hepatoblastomas have been reported. Karyotypic investigations have shown that most hepatoblastomas are diploid or hyperdiploid, often displaying trisomies for chromosomes 2 and 20. We have cytogenetically investigated an adult hepatoblastoma for which no previous karyotypic data exist. A hypertriploid stemline with multiple numerical and structural chromosomal aberrations, including +2 and +20, was found. In addition, the tumor displayed extensive clonal evolution with 11 subclones. Although the tumor thus displayed some chromosomal abnormalities commonly observed in childhood tumors, providing further support for the importance of these abnormalities in the development of hepatoblastoma, the level of genomic complexity seen in the present case has never been described in childhood hepatoblastomas and may suggest a different etiology or pathogenesis.     

Growth and function of human parathyroid tissue transplanted to athymic mice

The morphology, cell proliferation and function of transplanted normal, hyperplastic and adenomatous human parathyroid tissue was studied after transplantation to athymic mice. The iPTH was evaluated in relation to morphology. Human parathyroid tissue collected during surgery for hyperparathyroidism was implanted subcutaneously into athymic mice (nu/nu-BALB/cA) and was analysed 1, 4, 7 and 12 weeks after transplantation. The transplants were examined by light and electron microscopy and by autoradiography after continuous infusion of 3H-thymidine. The relative amount of viable tissue was evaluated using a computer image analysing programme. Graft function was evaluated by measuring human iPTH in mouse serum. A transplant take ratio of 93% was observed. The proliferation rate in adenoma grafts at 12 weeks after transplantation was five and fifteen times that observed in normal and hyperplastic transplants, respectively. In normal and adenoma groups, a continuous increase in iPTH concentrations was observed, but in the hyperplastic group the iPTH remained on the same level. The secretion of iPTH in relation to the amount of transplanted tissue and the fraction of viable tissue was at the same level at 12 weeks in normal and adenomatous grafted animals. In conclusion, human parathyroid tissue was successfully transplanted and maintained its original structure. The growth potential, but not the iPTH secretion, was significantly higher in adenoma grafts compared to grafts from hyperplastic and normal glands.     

Differential kinetics and distribution of antibodies in serum and nasal and vaginal secretions after nasal and oral vaccination of humans

Although nasal vaccination has emerged as an interesting alternative to systemic or oral vaccination, knowledge is scarce about the immune responses after such immunization in humans. In the present study, we have compared the kinetics and organ distribution of the antibody responses after nasal and oral vaccination. We immunized female volunteers nasally or orally with cholera toxin B subunit (CTB) and determined the specific antibody levels in serum and nasal and vaginal secretions, as well as the number of circulating antibody-secreting cells, before immunization and 1, 2, 3, 6, and 26 weeks thereafter. Nasal vaccination induced 9-fold CTB-specific immunoglobulin A (IgA) and 56-fold specific IgG antibody increases in nasal secretions, whereas no significant IgA increase was seen after oral vaccination. Both oral and nasal vaccination resulted in 5- to 6-fold CTB-specific IgA and 20- to 30-fold specific IgG increases in vaginal secretions. Strong serum responses to CTB were also induced by both routes of vaccination. A notable difference between nasal and oral vaccination was that the nasal route elicited a specific antibody response with a later onset but of much longer duration than did the oral route. We conclude from this study that the nasal route is superior to the oral route for administering at least nonliving vaccines against infections in the upper respiratory tract, whereas either oral or nasal vaccination might be used for eliciting antibody responses in the female genital tract.     

External and internal calibration of the MHC class I-specific receptor Ly49A on murine natural killer cells

Expression of the H-2Dd-specific inhibitory receptor Ly49A on murine NK cells is subject to MHC class I-dependent modulation in vivo. As a result, NK cells in H-2Dd-transgenic mice express low cell surface levels of Ly49A, whereas NK cells from nontransgenic C57BL/6 (B6) mice express high levels. The purpose of this study was to assess the role of MHC class I molecules on the NK cell itself vs those on surrounding cells in this calibration and to test whether the Ly49A levels are subject to regulation in mature NK cells also. Analysis of transgenic mice with mosaic expression of an H-2Dd/Ld transgene showed that MHC class I molecules on surrounding cells (external ligands) and on the NK cell itself (internal ligands) played distinct roles in the determination of Ly49A levels. External ligands were involved in down-regulation of Ly49A levels in vivo, whereas internal ligands kept the down-regulated levels of Ly49A low upon NK cell activation in vitro. Furthermore, in an experimental system based on adoptive transfer of spleen cells, receptor down-regulation of Ly49A occurred as a rapid adaptation process in mature NK cells after interaction with the H-2Dd ligand in vivo. This suggests that Ly49 levels are not fixed but can be changed in mature NK cells when they are exposed to a changed MHC class I environment.     

Bone growth and bone development in the presence of implants or after induced leg-lengthening studied using the Oxford Scanning Proton Microprobe

To respond to varying environmental demands the bone tissue in the body is under continual reconstruction throughout life. It is known that metallic elements are important for maintaining normal bone structure, but their roles are not well understood. More information about the effects of metal excess or deficiency is needed to help in the development of metallic bone implants and to improve the treatment of bone fractures and defects. The Oxford Scanning Proton Microprobe (SPM) is being applied in two studies involving metal ions in bone: (1) bone regrowth and bonding to titanium bone implants may be influenced by diffusion of Ti ions into the bone. We are using microPIXE to determine the metal ion content of bone developing in contact with implants of pure Nb, Ti and Ti alloys. (2) Bone lengthening as a surgical procedure is induced by fracturing the bone and allowing it to heal with a small gap between the fractured ends created by the use of external fixators. The gap can be slowly increased during the healing process to stimulate the production of new bone. The enzymes and other constituents of the developing bone need certain metals for their function. Using experimental animals we have studied the concentrations of the metals and whether a deficiency of trace metals limits the optimum rate of bone lengthening.     

A three-dimensional architecture for a parallel processingphotosensing array [silicon retina application]

A three-dimensional architecture for a photosensing array has been developed. This silicon based architecture consists of a 10 x 10 array of photosensors with 80 microns diameter, through chip interconnects to the back side of a 500 microns thick silicon wafer. Each photosensor consists of a 300 x 300 microns pn-junction photodiode. The following processes were used to create this photosensing architecture: 1) thermomigration of aluminum pads through an n-type silicon wafer; 2) creation of pn-junction photosensors on one side of the wafer; and 3) creation of aluminum pad ohmic contacts to the thermomigrated, through chip interconnects and the substrate on the back side of the wafer. The electrical and optical characteristics of the three-dimensional architecture indicates that it should be well suited as a photosensing framework around which a "silicon retina" could be built.     

Work environment functions in small enterprises in Sweden

In Sweden, a governmental commission has formed new strategies concerning the work environment with the aims of reducing employee absenteeism and re-employing those individuals who have already left employment as a result of bad working conditions. The main features in this new approach are: strengthening of the legislation; a responsibility for work injury costs; and a distinct rehabilitation responsibility. In this paper the authors discuss how these proposals suited the constraints and facilities of small enterprises, employing less than 50 persons. The results are based on interviews carried out with company directors, safety representatives and labour inspectors. The interviews revealed that the company directors had a negative attitude towards both the strengthening of legislation and responsibility for work injury costs. It was also revealed that the small companies lack both knowledge of how a good environment can be created and the state of their own work environment. It seems that the small companies cannot handle work environment questions in a systematic way without comprehensive education and training or without seeking expert assistance outside the company.     

The influence of food emulsifiers on fat and sugar dispersions in oils. III. Water content,purity of oils

The influence of water on the interactions between fat and sugar crystals dispersed in triglyceride (vegetable) oils was qualitatively estimated from sedimentation and rheological experiments. The experiments were performed both with and without food emulsifiers (monoglycerides and lecithins) present in the oil. The effects of minor natural oil components (nontriglycerides) on the interactions and on emulsifier adsorption to the crystals were examined by comparing a commercial refined oil and a chromatographically purified oil. The results show that water generally increases the adhesion between fat and sugar crystals in oils and also increases the surface activity of the oil-soluble food emulsifiers. Minor oil components give a small increase in the adhesion between fat and sugar crystals in oils, but do not influence the adsorption of food emulsifiers in any systematic way.     

Reported food intake and distribution of body fat: a repeated cross-sectional study

Background  

Body mass, as well as distribution of body fat, are predictors of both diabetes and cardiovascular disease. In Northern Sweden, despite a marked increase in average body mass, prevalence of diabetes was stagnant and myocardial infarctions decreased. A more favourable distribution of body fat is a possible contributing factor.