The effects of growth hormone in children with a GH deficiency: a report of 5 cases

The authors describe 5 cases, 3 boys and 2 girls, with idiopathic growth hormone deficiency in prepubertal age, treated with human growth hormone. In four of five cases the response to treatment with GH was relevant. Only in one case (F1) the response was negative. The results of this study confirm that rhGH is a safe and effective therapy in children with GHD.     

An Evaluation of Vaporizing Rates of SiO2 and TiO2 As Protective Coatings for Ultrahigh Temperature Ceramic Composites

For temperatures >1973 K, the thermodynamic and kinetic analyses of the major gaseous species for a liquid titanate layer would vaporize significantly less than a silicate layer, when considering these layers as a protective barrier for ultrahigh temperature ceramic composites. At 2500 K, the major species is TiO( g ) with p _{TiO( g )}=0.1 kPa compared with SiO( g ) with p _{SiO( g )}=1.3 × 10³ kPa at the Ti/TiO₂ and Si/SiO₂ equilibrium, respectively. The SiO( g ) attains a partial pressure greater than ambient pressure at 2500 K even with a thermodynamic activity of 0.01 considering equilibration with a silicide (e.g., TiSi _x ). In addition, at 2500 K the TiO₂ layer would vaporize at a rate of 0.23 mm/s compared with the SiO₂ layer's loss rate of 207 mm/s. Although the oxygen diffusivity and permeability through titanate solutions must be further analyzed, the thermodynamic and kinetic analyses for vaporization indicate a longer duration for a liquid titanate than for a liquid silicate layer at ultrahigh temperatures.     

Relaxation phenomena and structural modifications of substituted polythiophenes during the p-doping processes. An electrochemical and morphological study

Electrodes modified by polythiophenes bearing different substituents have been prepared and the behaviour of the conducting polymers has been studied with respect to the structural phenomena occurring in the correspondence to the doping and the relevant undoping processes. The effects of experimental parameters, such as undoping potential and time, have been investigated. The steric hindrance of the substituents on the polymer chain is demonstrated to play a fundamental role in determining the extent of compactness of the film, as induced by polarisation of the electrode at potentials at which the previously charged polymer is neutralised. Such a conclusion is in accordance with prediction of the electrochemical stimulated conformational relaxation model. Electrochemical AFM measurements have been performed in order to acquire a direct view of the morphological modifications of the polymer coatings during the reduction.     

Defective control of apoptosis, radiosensitivity, and spindle checkpoint in ataxia telangiectasia

We examined the regulation of apoptosis, radiosensitivity, and spindle checkpoint in response to DNA-damaging agents in ataxia telangiectasia (AT)-derived lymphoblastoid cell lines (AT-LCLs), which lack AT mutated (ATM) protein expression. In addition to the previous findings that AT-LCLs are defective in regulation of cell cycle at the G1, S, and G2-M checkpoints in response to X-ray irradiation (X-IR) and are highly sensitive to X-IR (J. Biol. Chem., 271: 20486-20493, 1996), we showed for the first time that AT-LCLs were defective in X-IR-associated spindle checkpoint control. The cells were also resistant to early apoptosis as much as LCLs derived from patients with Li-Fraumeni syndrome (LFS-LCLs). Terminal deoxynucleotidyl transferase-mediated nick end labeling assay of LCLs, however, demonstrated a significant increase in apoptotic cells among AT-LCLs cultured over a longer period after X-IR. These findings were in contrast to those of LFS-LCL, which showed very little increase in terminal deoxynucleotidyl transferase-mediated nick end labeling-positive population, even in cells with hyperploidy. Thus, although early apoptosis and cell cycle controls in response to DNA damage are disrupted in both ATM and p53 mutations, cells from AT patients are much more susceptible to late-onset apoptosis than those of LFS. These differences may depend on the level of accumulation of DNA damage and/or threshold that triggers late-onset cell death in ATM or p53 mutations. Our findings allow a better understanding of the role of ATM in p53-dependent and independent signal transduction pathways in response to DNA damaging agents.     

Casein haplotype structure in five Italian goat breeds

The aim of this work was to investigate the genetic structure of the casein gene cluster in 5 Italian goat breeds and to evaluate the haplotype variability within and among populations. A total of 430 goats from Vallesana, Roccaverano, Jonica, Garganica, and Maltese breeds were genotyped at alphas1-casein (CSN1S1), alphas2-casein, (CSN1S2), beta-casein (CSN2), and kappa-casein (CSN3) loci using several genomic techniques and milk protein analysis. Casein haplotype frequencies were estimated for each breed. Principal component analysis was carried out to highlight the relationship among breeds. Allele and haplotype distributions indicated considerable differences among breeds. The haplotype CSN1S1*F- CSN1S2*F-CSN3*D occurred in all breeds with frequencies >0.100 and was the most common haplotype in the Southern breeds. A high frequency of CSN1S1*0-CSN1S2*C-CSN3*A haplotype was found in Vallesana population (0.162). Principal component analysis clearly separated the Northern and Southern breeds by the first component. The variability of the caprine casein loci and variety of resulting haplotypes should be exploited in the future using specific breeding programs aiming to preserve biodiversity and to select goat genetic lines for specific protein production.     

Short communication: the beta-casein (CSN2) silent allele C1 is highly spread in goat breeds

Several single nucleotide polymorphisms have been identified in the goat milk casein genes, most of them modifying the amino acid sequence of the coded protein. At least 9 variants have been found in goat β-CN (CSN2); 6 of them were characterized at the DNA level (A, A1, C, E, 0, and 0′), whereas the other 3 variants were described only at the protein level. The recently identified silent A1 allele is characterized by a C→T transition at the 180th nucleotide of the ninth exon. In the present work, typing results from different breeds (3 Italian, 3 German, and a composite of African breeds for a total of 335 samples) demonstrated that the same mutation is carried by the CSN2*C allele. In addition, the T nucleotide at the 180th nucleotide of the ninth exon was always associated with CSN2*C in all the breeds analyzed. Thus, another silent allele occurs at goat CSN2 and can be named CSN2*C1. The much wider distribution of C1 with respect to the A1 allele indicates that the single nucleotide polymorphisms characterizing the silent mutation originated from CSN2*C. A method for the identification of this allele simultaneously with 5 of the 6 DNA-characterized alleles is also proposed. The mutation involved codifies for the same protein of the C allele; nevertheless, its location in the 3′ untranslated region of the gene might affect the specific casein expression.     

Short communication: Carora cattle show high variability in alpha(s1)-casein

The objective of this study was to analyze the genetic variability of milk proteins of the Carora, a shorthorned Bos taurus cattle breed in Venezuela and in other Southern American countries that is primarily used for milk production. A total of 184 individual milk samples were collected from Carora cattle in 5 herds in Venezuela. The milk protein genes α_s1-casein (CN) (CSN1S1), β-CN (CSN2), κ-CN (CSN3), and β-lactoglobulin (LGB) were typed at the protein level by isoelectrofocusing. It was necessary to further analyze CSN1S1 at the DNA level by a PCR-based method to distinguish CSN1S1*G from B. Increased variation was found in particular at the CSN1S1 gene, where 4 variants were identified. The predominant variant was CSN1S1*B (frequency = 0.8). The second most common CSN1S1 variant was CSN1S1*G (0.101), followed by CSN1S1*C (0.082). Moreover, a new isoelectrofocusing pattern was identified, which may result from a novel CSN1S1 variant, named CSN1S1*I, migrating at an intermediate position between CSN1S1*B and CSN1S1*C. Six cows carried the variant at the heterozygous condition. For the other loci, predominance of CSN2*A² (0.764), CSN3*B (0.609), and LGB*B (0.592) was observed. Haplotype frequencies (AF) at the CSN1S1-CSN2-CSN3 complex were also estimated by taking association into account. Only 7 haplotypes showed AF values >0.05, accounting for a cumulative frequency of 0.944. The predominant haplotype was B-A²-B (frequency = 0.418), followed by B-A²-A (0.213). The occurrence of the G variant is at a rather high frequency, which is of interest for selection within the Carora breed because of the negative association of this variant with the synthesis of the specific protein. From a cheese-making point of view, this variant is associated with improved milk-clotting parameters but is negatively associated with cheese ripening. Thus, milk protein typing should be routinely carried out in the breed, with particular emphasis on using a DNA test to detect the CSN1S*G variant. The CSN1S*G allele is likely to have descended from the Brown Swiss, which contributed to the Carora breed and also carries this allele.     

Adipose hormone-sensitive lipase preferentially releases polyunsaturated fatty acids from triglycerides

Rat adipose hormone-sensitive lipase-mediated release of fatty acids from triglycerides was studied in three model systems: i) cultured preadipocytes containing polyunsaturated fatty acid-enriched triglyceride; ii) perfused epididymal fat pads; and iii)in vitro incubations of crude preparations of hormone-sensitive lipase with synthetic triglyceride-analogues as substrates. We found that cultured preadipocytes challenged with 10μM norepinephrine tended to release more ω6 and ω3 polyunsaturated fatty acids than saturated fatty acids. Fat pads perfused with 10 μM norepinephrine preferentially released arachidonate and α-linolenate but tended to retain oleate and linoleate. Finally, crude preparations of hormonesensitive lipase released from the triglyceride-analogue substrates α-linolenate twice as fast as oleate. We conclude that rat adipose hormone-sensitive lipase preferentially releases polyunsaturated fatty acids from triglycerides. We suggest that this may be a mechanism by which these fatty acids are kept from being trapped in fat depots and maintained in the circulation.