[The influence of migration background and parental education on childhood obesity and the metabolic syndrome]. / Adipositas bei Kindern und Jugendlichen - Einfluss von Migrationshintergrund und Bildung der Eltern auf das Auftreten eines metabolischen Syndroms.

Obesity and metabolic syndrome are important risk factors for cardiovascular diseases. In this study, the influence of migration background and parental education on the degree of obesity and the presence of the metabolic syndrome (MS) in children and adolescents (N=492) requiring sociopediatric care were investigated. Two regression models were computed with the dependent variables BMI-SDS and MS, respectively. Age, gender, migration background, and parental education were used as independent variables. When controlling for age and gender, higher BMI-SDS were found among Turkish patients (ß=0.21; p=0.002) and patients with other migration backgrounds (ß=0.11; p=0.085) compared to German patients. The BMI-SDS values were also higher among patients from families with a low parental education level compared to those with a higher education level (ß=0.31; p<0.001). The key risk factor for MS is the BMI-SDS (OR: 8.9; p=0.011). No influence could be determined for migration background and parental education, when controlling for age, gender, and BMI-SDS. Obesity therapy should be increasingly tailored to the needs of identified risk groups. This will also allow for a targeted prevention of comorbidities.

Ethnicity and comorbidities in an overweight and obese multiethnic childhood cohort in Berlin.

AIM: This study aims to analyse the association between ethnicity, elevated metabolic parameters and metabolic syndrome (MS) in a multiethnic cohort of overweight to obese children and adolescents. METHODS: For 1053 patients, standard deviation of body mass index (BMI-SDS) was calculated and metabolic parameters (fasting blood glucose, fasting insulin, homeostasis model assessment-IR, lipids, blood pressure) were measured. MS was defined by WHO criteria. Bivariate and multivariate analyses were performed. Adjusted differences in BMI-SDS and metabolic parameters between different migration groups were assessed with linear regression models. The risk for MS was calculated with multiple logistic regression models. RESULTS: Forty-eight per cent of the children were German, 25% Turkish and 27% had another ethnicity. Concerning weight status, 23% are overweight, 31% obese and 46% extremely obese with higher rates among the immigrant population. Multivariable models indicate significant associations between elevated metabolic parameters and higher BMI-SDS values. Overall prevalence of MS was 32.3%. MS was detected significantly more often among Turkish patients (40.4%) compared to Germans (27.3%; p=0.02). Logistic regression analysis showed a greater risk for MS with older age (OR=1.09; p=0.003) and Turkish ethnicity (OR=1.62; p=0.02). CONCLUSION: Nearly all patients had symptoms of MS, and 40% had MS showing that this highly health-threatening condition is quite common. Therefore, effective therapy and prevention efforts must be developed for this high risk group. More migration-specific research regarding insulin resistance, MS and Type 2 DM is needed.

Fibrolamellar carcinoma of the liver: radiologic-pathologic correlation.

Fibrolamellar carcinoma is a malignant hepatocellular tumor with distinct clinical and pathologic differences from hepatocellular carcinoma. It differs from hepatocellular carcinoma in demographics, condition of the affected liver, tumor markers, and prognosis. Fibrolamellar carcinoma characteristically manifests as a large hepatic mass in adolescents or young adults (without gender predominance). Cirrhosis; elevated alpha-fetoprotein levels; and typical risk factors for hepatocellular carcinoma such as viral hepatitis, alcohol abuse, and metabolic disease are typically absent. Fibrolamellar carcinoma is characterized pathologically by cords of tumor cells surrounded by abundant collagenous fibrous tissue arranged in a parallel or lamellar distribution. Fibrotic lamellae often coalesce to form a central scar. Fibrolamellar carcinoma characteristically appears on radiologic images as a lobulated heterogeneous mass with a central scar in an otherwise normal liver. Radiologic evidence of cirrhosis, vascular invasion, or multifocal disease--findings typical of hepatocellular carcinoma--is uncommon in fibrolamellar carcinoma. Imaging features of fibrolamellar carcinoma overlap with those of other scar-producing lesions including focal nodular hyperplasia (FNH), hepatocellular adenoma and carcinoma, hemangioma, metastases, and cholangiocarcinoma. FNH, in particular, may simulate fibrolamellar carcinoma, since both have similar demographic and clinical characteristics. Because some believe that radiologic diagnosis of FNH is possible, it is important to understand the imaging appearance of fibrolamellar carcinoma to avoid misdiagnosing this malignant tumor as a FNH.

Amino-terminal analysis of tryptophan hydroxylase: protein kinase phosphorylation occurs at serine-58.

Tryptophan hydroxylase (TPH) catalyzes the rate-limiting and committed step in serotonin biosynthesis. Within this enzyme, two distinct domains have been hypothesized to exist, an amino-terminal regulatory domain and a carboxyl-terminal catalytic domain. In the present experiments, the functional boundary between the putative domains was defined using deletion mutagenesis. A full-length cDNA clone for rabbit TPH was engineered for expression in bacteria. Five amino-terminal deletions were constructed using PCR, i.e., Ndelta50, Ndelta60, Ndelta90, Ndelta106, and Ndelta116 (referring to the number of amino acids deleted from the amino terminus). Enzymatic activity was determined for each mutant after expression in bacteria. Whereas deletion of 116 amino acids (Ndelta116) abolished enzyme activity, all of the other amino-terminal deletions exhibited increased specific activity relative to the recombinant wild-type TPH. The ability of the cyclic AMP-dependent protein kinase (PKA) to phosphorylate members of the deletion series was also examined. Deletion of the first 60 amino-terminal residues abolished the ability of the enzyme to serve as a substrate for PKA, yet the native and Ndelta50 enzymes were phosphorylated. Moreover, a serine-58 point mutant (S58A) was not phosphorylated by PKA. In conclusion, the first 106 amino acids comprise a regulatory domain that is phosphorylated by PKA at serine-58. In addition, the boundary between regulatory and catalytic domains is analogous to the domain structure observed for the related enzyme tyrosine hydroxylase.

Recombinant ferritin: modulation of subunit stoichiometry in bacterial expression systems.

We describe a strategy for the creation of recombinant ferritin heteropolymers which mimic the natural heterogeneity of this protein. This method entailed the co-expression of cDNA for both ferritin H and ferritin L subunits in a single bacterium using either a bicistronic vector, in which both cDNAs were expressed from the vector, or a dual vector expression strategy, in which each subunit was expressed from a separate compatible plasmid in a single bacterial host. Electron microscopy and sucrose density gradient centrifugation demonstrated that ferritin assembled spontaneously in such bacteria to form catalytically active proteins of the expected size and shape. Isoelectric focusing revealed that protein isolated from any of these bacteria exhibited a restricted heterogeneity in subunit composition. Such multi-subunit recombinant ferritins spontaneously assembled in bacteria may be useful in further studies of ferritin assembly and function. Our results further suggest that varying expression levels is a simple way to alter levels of individual components within a multi-subunit recombinant protein, and that this approach may be of general utility in assessing the contribution of individual components to the function of multi-subunit proteins or protein complexes.

Role of H and L subunits in mouse ferritin.

Ferritin is an iron-binding protein composed of two subunits, H and L. Twenty-four of these subunits assemble to form apoferritins whose subunit composition varies in a characteristic way in different tissues. Using recombinant proteins, we have assessed the role of H and L subunits in mouse ferritin function and compared these to human ferritin subunits. We report that mouse ferritin subunits exhibit considerable functional similarity to their human counterparts, including a prominent role of the H subunit in the facilitation of rapid iron uptake, and a key role of amino acid residues Glu-62 and His-65 in this process. In addition, amino acid residues important to assembly of the protein are conserved between mouse and human, permitting the formation of fully functional hybrid proteins containing both mouse and human subunits. However, murine and human ferritin H subunits also evidenced substantial functional differences; murine ferritin H showed a consistent reduction in iron uptake activity relative to human ferritin H. Creation of chimeric human/mouse ferritin H subunits by "helix swapping" mapped the domain of the protein critical to this activity difference to the DE helix. These findings suggest a novel functional role for carboxyl-terminal domains of the ferritin H subunit.

A carboxyl terminal leucine zipper is required for tyrosine hydroxylase tetramer formation.

Tyrosine hydroxylase catalyzes the rate-limiting reaction in the biosynthesis of the catecholamine neurotransmitters and hormones (dopamine, norepinephrine, and epinephrine). Rat tyrosine hydroxylase exists, in its native form, as a tetramer composed of identical 498 amino acid subunits. There is currently no information describing the molecular interactions by which the four monomeric tyrosine hydroxylase subunits assemble into an active tetramer. Mutational analysis was performed on bacterially expressed enzyme to assess the role of a putative C-terminal leucine zipper in the assembly of subunits into the tetrameric holoenzyme. Deletion of the C-terminal 19 amino acids, or mutation of a leucine residue (to an alanine), converts the enzyme from a tetrameric to a dimeric form that exhibits greater structural heterogeneity. This change in macromolecular form is accompanied by a 75% (deletion mutation) to 20% (Leu-->Ala mutation) reduction in specific activity of the enzyme. This represents the first report of the functional involvement of a region containing a leucine zipper motif in the assembly and activity of a neuronal enzyme.

Recombinant rabbit tryptophan hydroxylase is a substrate for cAMP-dependent protein kinase.

A full-length cDNA clone for rabbit tryptophan hydroxylase (TPH) was modified and subcloned into a bacterial expression vector. Expression of this gene in the protease-deficient strain of bacteria, BL21[DE3], produced TPH immunoreactive protein which exhibited enzyme activity. Treatment of the recombinant enzyme (in bacterial extracts) with the purified catalytic subunit of the cAMP-dependent protein kinase and [gamma-32P]-ATP resulted in specific phosphorylation of TPH. This expression system provides a means of generating and purifying large amounts of this important enzyme. Moreover, these experiments establish that TPH will serve as an in vitro substrate for cAMP-dependent protein kinase.

Energy deposition in iron pentacarbonyl ions undergoing surface-induced dissociation in a Fourier transform mass spectrometer.

Internal energy deposition into iron pentacarbonyl positive ions undergoing surface-induced dissociation (SID) in a Fourier transform mass spectrometer is estimated from the abundances and known critical energies of the product fragment ions. A narrow energy distribution, comparable to that reported in earlier BQ and tandem quadrupole SID studies of the same compound, is observed. As judged by the ratio of fragment ions to incident parent ions observed, SID of iron pentacarbonyl in the 3 T Fourier transform mass spectrometer is more efficient, but results in lower conversion of laboratory to internal energy. This may be a result of the more shallow collision incidence angle employed in the Fourier transform mass spectrometer measurements (a few degrees), which contrasts with the 32-60° collision angles used in the earlier BQ and tandem quadrupole mass spectrometry studies. Collision-induced dissociation with He under single collision conditions is also reported, Not unexpectedly, conversion of kinetic to internal energy was lower than found in a previous Fourier transform mass spectrometer study of the iron pentacarbonyl cation employing argon as collision gas under multiple collision conditions.

[Overlooked osteochondral fractures of the knee-joint area among juveniles]. / Ubersehene osteochondrale Frakturen im Kneigelenkbereich bei Jugendlichen.

Osteochondral fractures among juveniles are the subject being reported. Thereby it is emphasized that the fractures in the early stages could often be overlooked. The existing pains, the effusions of blood as well as the mechanism of the accident often lead to the term "distorsion" as a wrong diagnosis. X-ray examinations can be unsatisfactory in the early stages. In 3 up to 4 weeks it is recommendable to repeat the X-ray examinations in the case of sustained pains. After that tomographies and tangential roentgenograms of the patella are also valuable. In early cases the therapy can be carried through conservatively as a general rule. Later on a surgical treatment is advisable. Cases of illness which are not treated lead to degenerative effusions of the joint and in the long run they lead to degenerative alterations of the joint.

[Investigation on the morphokinetic reactions of the rat liver to ether anaesthesia of different length (author's transl)]. / Untersuchung über die morphokinetische Reaktion der Rattenleber auf Athernarkosen verschiedener Dauer

The nuclear volumes were measured in the central, intermediate and peripheral zone of the classic liver lobule of adult male albino rats exposed to ether anaesthesia lasting 15, 40 and 80 min. Related to control animals there was a significantly lower nuclear size after a 40 min duration of narcosis and a significant higher volume after 80 min in the central part of the lobule. With a slight but not significant decrease of nuclear volume in the intermediate zone after 15 min and a significant increase after 80 min respectively, the peripheral lobular region constantly showed significantly smaller nuclei. But here, too, a disappearance of decrease was recorded after 80 min. The interpretation of the data is based upon a typical distribution of cell organelles, enzymatic pathways, and metabolites in the different zones of the hepatic lobule. The intensity of reaction and appearance of diminution in nuclear volume, indicating a functional depression and probably accentuated by a circular dependent low O2-tension of tissue, is interpreted in connection with different local concentrations of ether. An improvement of the blood flow by augmental local metabolites and an increased arterial influx presumably support the recovery and favour a concentration-dependent induction of microsomal enzymes in the central part of the lobule especially.