Medial cell mixing during axial morphogenesis of the amphibian embryo requires cadherin function

A truncated form of Xenopus E-cadherin (deltaE-cad) comprising the cytoplasmic and transmembrane domains was overexpressed generating a dominant negative mutation in the urodelan amphibian embryo Pleurodeles waltl. deltaE-cad mRNA and rhodamine-lysinated-dextran (RLDx) cell lineage tracer were microinjected into 32-cell stage blastomeres which contribute principally to the notochord and central nervous system. deltaE-cad expression causes defects in forebrain and hindbrain formation coupled with the development of supernumerary vesicles. Duplication of the notochord also occurs due to the retardation of medial cell intercalation with correlated duplications of spinal cord and somites. These results emphasize the role of cadherins in mediating cell-cell adhesion in early amphibian embryogenesis. They extend to Pleurodeles the observations made in Xenopus, illustrating that despite differences in morphogenetic processes, the molecular mechanisms are conserved in these two species.     

Skeletal maturation in adolescence: a comparison between the Tanner-Whitehouse II and the Fels method

In this longitudinal study, skeletal ages assessed with the Fels method and the Tanner-Whitehouse II method (TW II) were compared for boys (n = 30) and girls (n = 30) with a mean chronological age between 12 and 16 years. The subjects, participating in the Amsterdam Growth and Health Study, were measured annually between 1977 and 1980, which resulted in four radiographs of the left hand and wrist of every individual. For boys, the mean TW II skeletal age was 0.32 years older than the mean Fels skeletal age (sd 0.50). Tested at the subsequent chronological ages, the mean TW II skeletal ages were 0.05-0.47 years older, the differences being statistically significant at the mean ages of 13, 14 and 15 years. For girls, the mean TW II skeletal age was 0.20 years younger than the mean Fels skeletal age (sd 0.69). At the subsequent chronological ages, the mean TW II skeletal ages were 0.03 to 0.35 year younger, the differences being statistically significant at the mean chronological ages of 14 and 15 years. As a consequence of the differences between the methods, application of the Fels method resulted in classifying a smaller percentage of boys (10%) as rapid maturers, and a higher percentage (6.7%) of boys as normal maturers in comparison to the TW II method. For girls, a higher percentage of female adolescents were classified as rapid (16.7%) and slow maturers (13.3%), but a smaller percentage was classified as normal mature (30%). Differences in the skeletal ages can be ascribed to differences in maturation of the reference population, but also to fundamental differences in the statistical methods of the scoring system and the scales of maturity. CONCLUSION: There is no agreement in skeletal ages assessed according to the TW II method and the Fels method in adolescence.     

Expression of putative fatty acid transporter genes are regulated by peroxisome proliferator-activated receptor alpha and gamma activators in a tissue- and inducer-specific manner

Regulation of gene expression of three putative long-chain fatty acid transport proteins, fatty acid translocase (FAT), mitochondrial aspartate aminotransferase (mAspAT), and fatty acid transport protein (FATP), by drugs that activate peroxisome proliferator-activated receptor (PPAR) alpha and gamma were studied using normal and obese mice and rat hepatoma cells. FAT mRNA was induced in liver and intestine of normal mice and in hepatoma cells to various extents only by PPARalpha-activating drugs. FATP mRNA was similarly induced in liver, but to a lesser extent in intestine. The induction time course in the liver was slower for FAT and FATP mRNA than that of an mRNA encoding a peroxisomal enzyme. An obligatory role of PPARalpha in hepatic FAT and FATP induction was demonstrated, since an increase in these mRNAs was not observed in PPARalpha-null mice. Levels of mAspAT mRNA were higher in liver and intestine of mice treated with peroxisome proliferators, while levels in hepatoma cells were similar regardless of treatment. In white adipose tissue of KKAy obese mice, thiazolidinedione PPARgamma activators (pioglitazone and troglitazone) induced FAT and FATP more efficiently than the PPARalpha activator, clofibrate. This effect was absent in brown adipose tissue. Under the same conditions, levels of mAspAT mRNA did not change significantly in these tissues. In conclusion, tissue-specific expression of FAT and FATP genes involves both PPARalpha and -gamma. Our data suggest that among the three putative long-chain fatty acid transporters, FAT and FATP appear to have physiological roles. Thus, peroxisome proliferators not only influence the metabolism of intracellular fatty acids but also cellular uptake, which is likely to be an important regulatory step in lipid homeostasis.     

Hypotensive action of bromocriptine in the DOCA-salt hypertensive rat: contribution of spinal dopamine receptors

Clinical islet transplantation is potentially the treatment of choice for people with type I diabetes. Rates of insulin independence in islet transplant recipients are disappointingly low, and the relative contribution of the rejection response compared with the loss of islet function is still unclear. We have compared the mixed lymphocyte islet coculture (MLIC) with the mixed lymphocyte acinar cell coculture (MLAC) and the mixed lymphocyte response (MLR) as in vitro models of allograft rejection to MHC and tissue-specific antigens expressed by human islets and acinar cells. The reduced number of MHC class II antigen-positive cells in islets and acinar tissue compared to those in the stimulator lymphocyte population of the MLR, correlated with a reduced proliferative response in the MLIC and MLAC. Enhancement of MHC class II antigen expression by islets using TNFalpha and IFNgamma did not increase their stimulatory capacity in the islet cocultures, which may have been due to a corresponding absence of B7 expression. The lack of T cell proliferation to acinar cells despite cytokine-induced enhancement of MHC class II expression and detectable B7 expression appeared to be due to the inhibitory effect of exocrine enzymes on lymphocyte proliferation. In conclusion, we suggest that a rejection response to islets and acinar tissue is possible due to the accompanying MHC class II-positive cells and that, in this model, islet and acinar-specific antigens do not significantly contribute to that response. Acinar cells may have the potential to stimulate lymphocytes directly, but this was not evident by proliferation in the MLAC. Rejection appears to contribute to the low survival rate of human islet allografts, but it is unlikely that this is the sole explanation, and other factors should be considered.     

A comparison of the bactericidal and photobactericidal activities of aminoacridines and bis(aminoacridines)

The nasal cavity is a rare location for primary malignant melanoma, borne out by the few cases reported in the literature since 1940. Rarest of all is nasal melanoma in a patient with oculocutaneous albinism. An albino subject, aged 33, was referred to us with this diagnosis. Because of the numerous metastases in the liver and left lung, we did not advise radical surgical intervention and, despite hyperfractionated high dose radiotherapy and chemo-immunotherapy, the advanced stage of disease caused the death of the patient within a year. We have reviewed the diagnostic, clinical and therapeutic aspects, and the literature on melanomas of the nasal cavity in albino subjects. We performed a Medline literature search, examining only 'extensive' papers and excluding abstracts or case reports presenting poor data.     

Human vertebral body apparent and hard tissue stiffness

Cancellous bone apparent stiffness and strength are dependent upon material properties at the tissue level and trabecular architecture. Microstructurally accurate, large-scale finite element (LS-FE) models were used to predict the experimental apparent stiffness of human vertebral cancellous bone and to estimate the trabecular hard tissue stiffness. Twenty-eight LS-FE models of cylindrical human vertebral cancellous bone specimens (8 mm in diameter, 9.5 mm in height, one each from twenty-eight individuals) were generated directly from microcomputed tomography images and solved by a special purpose iterative finite element program. The experimental apparent stiffness and strength of the specimens were determined by mechanical testing to failure in the infero superior direction. Morphometric measurements including bone volume fraction (BV/TV), three eigenvalues of the fabric tensor and average P(L) were also calculated. The finite element estimate of apparent stiffness explained much of the variance in both experimental apparent stiffness (r2=0.89) and experimental apparent strength (r2=0.87). Stepwise linear regression analysis demonstrated that the LS-FE estimated apparent stiffness was the only significant predictor of experimental apparent stiffness and strength when it was included with all measured morphometric values. Hard tissue stiffness was quite variable between individuals (mean, 5.7 GPa; S.D. 1.6 GPa), but was not significantly related to age, sex, race, weight or morphometric measures for this sample.     

Disruption of the DT diaphorase (NQO1) gene in mice leads to increased menadione toxicity

NAD(P)H:quinone oxidoreductase 1 (NQO1) is a flavoenzyme that catalyzes two-electron reductive metabolism and detoxification of quinones and their derivatives leading to protection of cells against redox cycling and oxidative stress. To examine the in vivo role of NQO1, a NQO1-null mouse was produced using targeted gene disruption. Mice lacking NQO1 gene expression showed no detectable phenotype and were indistinguishable from wild-type mice. However, NQO1-null mice exhibited increased toxicity when administered menadione compared with wild-type mice. These results establish a role for NQO1 in protection against quinone toxicity. The NQO1-null mice are a model for NQO1 deficiency in humans and can be used to determine the role of this enzyme in sensitivity to toxicity and carcinogenesis.