Inhibition of ethanol metabolism by fructose in alcohol dehydrogenase-deficient deer mice in vivo

The purpose of this work was to compare the roles of a newly described mitochondrial dehydrogenase and catalase in ethanol elimination in deer mice deficient in alcohol dehydrogenase (ADH-). Fructose was used because of its well-known ability to stimulate dehydrogenase-dependent ethanol metabolism. Rates of ethanol metabolism in vivo were decreased significantly by about 60% in a dose-dependent manner by fructose in deer mice fed an ethanol-containing or a corn oil control diet. In addition, rates of metabolism of methanol, a selective substrate for catalase in rodents, were similar to rates of ethanol elimination and were decreased from 6.9 +/- 1.0 to 1.7 +/- 0.5 mmol/kg/h by fructose, supporting the hypothesis that catalase and not a mitochondrial dehydrogenase predominates in ethanol oxidation in ADH-deer mice. Glycolate, a substrate for peroxisomal H2O2 generation, reversed the inhibition of alcohol metabolism by fructose completely, indicating that fructose did not inhibit catalase directly. As expected, the ATP/ADP ratio was decreased by fructose significantly from 4.2 +/- 0.4 to 2.4 +/- 0.4 in deer mouse livers. These data are consistent with the hypothesis that fructose decreases catalase-dependent ethanol metabolism in vivo by inhibiting hepatic H2O2 generation.     

Age at Introduction of Solid Food and Obesity Throughout the Life Course

Objective

This study aimed to examine the association between age at solid food (SF) introduction and obesity throughout the life course.

Methods

Among 31,816 mother– nurse daughter dyads in the Nurses' Mothers' Cohort Study and the Nurses' Health Study II, information was collected on age at SF introduction, body somatotype at ages 5 and 10, and Body Mass Index at age 18 and in adulthood. Odds ratios (ORs) and 95% confidence intervals (95% CIs) for obesity throughout life were estimated using logistic regression models with adjustment for parental and nurse daughter covariates.

Results

Nurse daughters introduced to SF at ≥ 9 months versus 6 to 9 months had marginally higher age‐adjusted (OR: 1.21; 95% CI: 1.01, 1.47) and covariate‐adjusted (OR: 1.22; 95% CI: 1.01, 1.47) odds of obesity at age 5. Age at SF introduction was not related to obesity at ages 10 and 18 or in adulthood.

Conclusions

Late age at SF introduction was marginally associated with obesity at age 5, but this association did not persist throughout the life course.     

The Callimico goeldii (Primates,Platyrrhini) genome: Karyology and middle repetitive (LINE-1) DNA sequences

Callimico goeldii (Goeldi's marmoset) is a neotropical primate with 2n=47,X1X2Y in the male, and 2n=48,X1X1X2X2 in the female, due to a Y-autosome translocation. Karyological comparisons of Callimico, Callithrix jacchus and Cebus apella suggest that Callimico is a member of the Callitrichidae. Isozyme data and restriction mapping of LINE-1 repetitive elements in these species and in a variety of other neotropical primates confirm these findings and supply strong evidence for including Callimico in the Callitrichidae. On leave from: Genetics Section, Instituto Nacional do Cancer (Rio de Janeiro)/Department of Genetics, Universidade Federal do Rio de Janeiro, Brazil     

Analysis of D2 d : a D-region class I gene

The mouse major histocompatibility complex is composed of several genes arranged into the K, D, Qa, and Tla regions. The D region of the BALB/c mouse includes genes D2 ^d , D3 ^d , and D4 ^d , in addition to H-2D ^d and H-2L ^d . We have determined the DNA sequence of the D2 ^d gene and compared it with the known sequences of several class I genes. The exon/intron structure of the D2 ^d gene is similar to other class I genes. It also contains similar 5 regulatory elements. A frameshift occurs in exon seven, resulting in a gene product with a truncated cytoplasmic tail. To examine the surface expression of the D2^d molecule, we generated an exon-shuffled construct containing the promoter and exons 1–3, encoding the signal peptide, 1, and 2 external domains of the D2 ^d gene linked to exons 4–8, encoding the 3, transmembrane and cytoplasmic domains, of the H-2D ^d gene. The construct was transfected into mouse L cells, and a protein was detected at the cell surface by a monoclonal antibody (mAb) specific for the 3 domain of H-2D^d, as well as by other class I-specific mAbs. Although D2^d is expressed at low levels, it may be a functional class I gene that most probably evolved from a Qa region gene.     

Analysis ofH-2 mutants: Evidence for multiple CML target specificities controlled by theH-2K b gene

C57BL/6 (H-2 ^b ) mice and two mutants derived from this strain, B6.C-H-2 ^ba (Hz1) andE6-H-2 ^bd (M505), were studied in a number of functional tests, in vitro and in vivo, that assay for differences at theH-2 complex. All three strains give rise to reciprocal mixed lymphocyte reactivity (MLR) and cell-mediated lympholysis (CML) in vitro as well as graft-host reactivity (GVHR) and skin graft rejection in vivo. Analysis for cross-reactivity between these strains in CML revealed that the gained antigens in each mutant do not cross-react, and that Hz1 has lost an antigen shared by C57BL/6 and M505 strains. In addition, spleen cells from B10.A(4R) mice, which differ from theH-2 ^b haplotype only at theK end of theH-2 complex, recognize a common antigen shared by all three strains tested. Provided that the mutations occurred in theH-2K ^b gene, these data indicate that a) there are at least three antigenic specificities coded for by theH-2K ^b gene(s) that serve as targets for receptors on thymus-derived (T) cells in CML; b) since C57BL/6 strain mice and the mutants are serologically indistinguishable on a qualitative basis, the antigens recognized by the receptors on T cells and by humoral H-2 antibody are nonidentical; and c) mutation in theH-2K ^b locus itself can give rise to allogeneic recognition phenomena such as MLR and GVHR.     

Factors influencing the rate of electron transport in different respiratory pathways of bacteria

The rate of electron transfer by a respiratory pathway as dependent on pH, temperature, concentration of cyanide and concentration of azide was followed in washed non-growing cells ofCitrobacter. Three respiratory pathways leading to three terminal electron acceptors, i.e. oxygen, tetrathionate and nitrate, were investigated. It was found that these pathways mutually differ in their response to pH, temperature, cyanide and azide and conditions favouring inhibition or stimulation of one electron transport pathway relatively to the other two pathways were established.     

Analysis of hybrid H-2D and L antigens with reciprocally mismatched aminoterminal domains: functional T cell recognition requires preservation of fine structural determinants

Studies of immune recognition of hybrid class I antigens expressed on transfected cells have revealed an apparent general requirement that the N(alpha 1) and C1(alpha 2) domains be derived from the same gene in order to preserve recognition by virus-specific H-2-restricted and allospecific T cells. One exception has been the hybrid DL antigen in which the N domain of H-2Ld has been replaced by that of H-2Dd. Cells bearing this molecule serve as targets for some virus and allospecific CTL. Because cells expressing the reciprocal hybrid LD (N domain of H-2Dd replaced by that of H-2Ld) antigen have not been available, it has not been possible to evaluate whether this exception stemmed from the relatedness of H-2Ld and H-2Dd or whether the DL antigen fortuitously preserved some function of the parent molecule as a rare exception. To assess this question, and to evaluate the contribution of the N and C1 domains of H-2Ld and H-2Dd to serologic and T cell recognition, we have constructed the reciprocal chimeric gene pLD (the N exon of H-2Ld substituted for that of H-2Dd), introduced this into mouse L cells by DNA-mediated gene transfer, and analyzed the expressed product biochemically, serologically, and functionally. Transformant L cells expressing either LD or DL antigens were both reactive with a number of anti-H-2Ld or anti-H-2Dd N/C1-specific monoclonal antibodies, indicating the preservation in the hybrid molecules of determinants controlled by discrete domains. Mab binding was generally greater with cells expressing hybrid DL antigen than with those transformants expressing LD molecules. Moreover, the amount of beta 2M associated with DL antigens was more than that associated with LD. Cells expressing hybrid DL antigens were recognized as targets by bulk and cloned allospecific anti-H-2Dd and anti-H-2Ld CTL, whereas cells expressing LD molecules were not recognized by any of the T cells tested. VSV-specific H-2Ld-restricted CTL failed to lyse VSV-infected targets expressing either DL or LD. These results indicate that T cell reactivity of cells expressing the DL hybrid antigen is an exception to the observed general requirement for class I antigens to possess matched N and C1 domains for functional T cell recognition by T cells restricted to parental antigens.(ABSTRACT TRUNCATED AT 400 WORDS)     

Effect of CNS-active drugs on TRH-induced prolactin release

The effects of several central acting drugs upon thyrotropin-releasing hormone (TRH)-induced increases in prolactin (PRL) release were compared in estrogen-primed male rats. Administration of the serotonin antagonist, p-chlorophenylalanine, or the opiate antagonist, naltrexone, did not alter TRH-induced release of PRL. Pre-treatment with either the dopamine agonist, piribedil, or the cholinergic agonist, pilocarpine, resulted in significantly reduced TRH-induced PRL release. Pilocarpine did not inhibit the TRH-induced increase in PRL release when rats were first pre-treated with the dopamine receptor blocker, haloperidol. These results indicate that the dopaminergic and cholinergic systems can modify TRH-induced release of PRL in vivo.     

Hyperoxia alters effect of calcium on rat alveolar macrophage superoxide production

The effect of hyperoxia on the Ca2+ dependence of stimulated superoxide anion radical (O2-.) production (the respiratory burst) of rat alveolar macrophages was investigated. Enhancement of the concanavalin A (con A)-stimulated respiratory burst by extracellular Ca2+ was suppressed by O2 exposure. Similarly, the inhibitory effect of verapamil on the con A-stimulated respiratory burst was reduced by O2 exposure. O2 exposure also inhibited con A stimulation that was independent of Ca2+ entry. Exposure to O2 also caused a decline in O2-. production stimulated by either A23187 or phorbol myristate acetate (PMA). With A23187 stimulation, extracellular Ca2+ was essential for either air-exposed (control) or O2-exposed cells. With PMA, stimulation was independent of extracellular Ca2+ for either air or O2-exposed macrophages and verapamil did not inhibit. Free intracellular Ca2+ concentration ([Ca2+]i) was measured in control and O2-exposed alveolar macrophages. Hyperoxic exposure did not alter [Ca2+]i in unstimulated cells. In controls, con A stimulated an immediate increase in [Ca2+]i followed by a rapid decrease and a second rise and fall. The second elevation was suppressed by verapamil or ethyleneglycol-bis (beta-aminoethylether)-N,N'-tetraacetic acid or O2 exposure. The results of both the respiratory burst assays and measurement of con A-stimulated changes in [Ca2+]i suggest that Ca2+ entry involved in stimulus-response coupling is suppressed in cellular O2 toxicity.