ISSN:0031-3998    

出版商:OVID    

年代:2002

数据来源: OVID

ISSN:0031-3998    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Linear growth occurs during development and the childhood years until epiphyseal fusion occurs. This process results from endochondral ossification in the growth plates of long bones and is regulated by systemic hormones and paracrine or autocrine factors. The major regulators of developmental and childhood growth are GH, IGF-I, glucocorticoids, and thyroid hormone. Sex steroids are responsible for the pubertal growth spurt and epiphyseal fusion. This review will consider interactions between GH, IGF-I, glucocorticoids, and thyroid hormone during linear growth. It is well known from physiologic and clinical studies that these hormones interact at the level of the hypothalamus and pituitary. Interacting effects on peripheral tissues such as liver are also well understood, but we concentrate here on the epiphyseal growth plate as an important and newly appreciated target organ for convergent hormone action.

ISSN:0031-3998    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Antibacterial factors were purified from human adenoid glands by tissue extraction and consecutive steps of reversed-phase chromatography and assayed for bactericidal activity against the airway pathogenMoraxella catarrhalisand alsoEscherichia coliandBacillus megaterium. One of the most active components isolated from adenoids was identified by N-terminal sequence analysis and mass spectrometry as high mobility group box chromosomal protein 1 (HMGB1). This novel finding was further substantiated by Western blot analysis, demonstrating a protein of expected size reactive with HMGB1 antiserum. Local synthesis was confirmed by reverse-transcriptase PCR andin situhybridization. Adenoid-derived HMGB1 and recombinant HMGB1 revealed comparable antibacterial activity at high rate. More than 95% of bacteria were eradicated within 5 min by HMGB1 in the cultures. Secretion from the adenoid gland surface was also demonstrated to contain antibacterial activity, mainly mediated by &agr;-defensins, but not by HMGB1. We conclude that HMGB1, produced and stored intracellularly in the adenoid gland, contributes to the local antibacterial barrier defense system in the upper respiratory tract.

ISSN:0031-3998    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Platelet-activating factor (PAF) has been implicated in the pathogenesis of gastrointestinal diseases such as necrotizing enterocolitis, Crohn’s disease, and ulcerative colitis. However, neither the physiologic role of PAF in the intestine, nor the mechanisms by which PAF participates in the pathogenesis of disease are well understood. The aim of the present study was to determine the direct effect of PAF on intestinal epithelial cell ion transport, and to delineate the mechanisms of regulation. Ion transport was evaluated by measuring short circuit current (Isc) in HT29-CL19A cell monolayers using Ussing chambers. PAF receptor polarity was assessed using domain-selective biotinylation followed by immunoprecipitation and streptavidin blotting of intact epithelial monolayers. PAF (1–200 &mgr;M) stimulated Iscthat followed the direction of a Cl−gradient and was specifically inhibited by the Cl−channel blockers glybenclamide, 2,2′ iminodibenzoic acid and 4,4′ diisothiocyanostilbene-2, 2′ disulfonic acid, but was unaffected by the inhibition of prostaglandin synthesis with indomethacin. Stimulated Iscwas only detected after apical addition of PAF, correlating with the results of biotinylation experiments indicating an exclusive apical polarity of the PAF receptor. PAF receptor antagonists CV6209 and octylonium bromide abolished PAF-stimulated Isc. Thus, mucosal acting PAF directly and specifically stimulates ion transportviaactivation of an apical Cl−channel in intestinal epithelial cell monolayers independent of prostaglandin biosynthesis.

ISSN:0031-3998    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

The aim of the present study was to assess the association of prenatal exposure to hexachlorobenzene (HCB) and other organochlorine compounds with anthropometric measures at birth. A total of 98 mother-infant pairs (83% of all children born in a specific area polluted with HCB in the period 1997–1999) were recruited after giving written consent. Levels of organochlorine compounds were measured in 72 maternal serum samples at delivery and in 70 cord serum samples. Of the organochlorines measured in cord serum, median levels of HCB were higher than for the other compounds (median of HCB = 1.13 ng/mL, median of dichlorodiphenyl dichloroethylene = 0.85 ng/mL, and median of total polychlorinated biphenyls = 0.27 ng/mL). Premature newborns had higher concentrations of HCB [1.94 ng/mL among prematuresversus1.10 among nonprematures (p< 0.10)], dichlorodiphenyl dichloroethylene [2.40versus0.80 (p< 0.05)], and polychlorinated biphenyls in cord serum [0.70versus0.14 (p< 0.10)]. Those infants born with a small length for gestational age had higher levels of HCB in cord serum than those with an adequate length for gestational age [1.64 ng/mLversus1.00 ng/mL (p< 0.05)]. In addition, HCB cord serum levels were negatively associated in a dose-response way with crown-heel length [for each doubling of the dose there was a decrease of 0.46 (SE = 0.22) cm] after adjusting for smoking, gestational age, and other organochlorine compounds. The associations of dichlorodiphenyl dichloroethylene and polychlorinated biphenyls with length were not significant. The results did not vary when stratified for prematurity. These data suggest that HCB reduces intrauterine physical linear growth.

ISSN:0031-3998    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

In earlier work, postnatal growth restriction (more marked in males) was observed in a model of transgenic mice with liver-specific expression of human IGF binding protein-1. This was associated with diminished plasma IGF-I levels, the cause of which remained unexplained. Subsequently, abnormalities of CNS development were ascertained, justifying investigation of the somatotrophic axis. Pituitary gland weight in transgenic animals was reduced proportionally to body weight. Immunohistochemical examination of the pituitaries in 3- to 4-mo-old mice revealed somatotrophs of normal size in homozygotes, but density was decreased to approximately two thirds of that in wild-type siblings (p= 0.001). The same was true of lactotrophs. The GH content of the pituitary was significantly reduced in heterozygotes (p< 0.02) and more so in homozygotes (p< 0.0003), although the GH/total protein ratio was similar to that in wild types. Pituitary perifusion experiments showed thatin vitrothe amounts of GH secreted under basal conditions and under GH-releasing hormone stimulation were similar in transgenic and wild-type mice. Ten days of treatment with human GH (100 &mgr;g/d) in 45-d-old transgenic and wild-type mice provoked significant weight gain (p= 0.02) in all animals, the means being 12.4% for homozygotes and 10.4% in heterozygotes, as opposed to 5.8% in wild-type mice. The increase in weight tended to correlate with an increase in plasma IGF-I. From these results, we conclude that the reduced plasma IGF-I in IGF binding protein-1 transgenic mice may result from insufficient GH production by the depressed number of somatotrophs, possibly associated with functional alteration of hypothalamic control.

ISSN:0031-3998    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Myelin oligodendrocyte glycoprotein (MOG) is a quantitatively minor glycoprotein of the CNS localized preferentially on the outermost myelin lamellae and the oligodendrocyte plasma membrane. In several animal models, MOG displays highly immunogenic properties by inducing a severe multiple sclerosis-like disease, characterized by inflammatory demyelinating lesions. Immunologic findings implicate MOG as a target autoantigen in multiple sclerosis. We have performed a molecular study on the MOG gene by sequencing the promotor and the entire coding region, as well as the exon-intron boundaries, in 75 children with multiple sclerosis. A total of five unknown polymorphic sites in the promotor region not affecting any of the putative cis-acting transcriptional regulation motifs as well as nine additional base changes in four different exons each with similar distribution in patients and controls (n= 100) were detected. Exon 2 coding for the Ig-like domain revealed two rare heterozygous missense mutations, possibly altering favorable conformational epitopes (P43H; R66P). P43 is part of the encephalitogenic epitope MOG35–55. A putative C1q binding site in the C″-D loop of the Ig superfamily motif encompasses R66. In conclusion, the polymorphisms observed do not provide evidence to support a significant role for MOG in multiple sclerosis susceptibility.

ISSN:0031-3998    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Although mitogen-activating protein (MAP) kinases are crucial signal transduction molecules regulating cellular proliferation, differentiation, and morphology, their ontogenic changes in the small intestine have not been analyzed. Also, it remains unknown which pathway of activated MAP kinases regulates the expression of brush border membrane hydrolases during growth. Therefore, we have analyzed the mucosal distribution, ontogeny, and responses to insulin and to inhibitors of p44, p42, and p38 MAP kinases in immature and mature enterocytes using Western blot analysis and autoradiography after immunoprecipitation, immunohistochemistry, andin vitrophosphorylation assays. Between d 10 and 40 postpartum, diphosphorylated active p44/p42 extracellular regulated protein kinases (ERKs) increased in abundance compared with total immunoprecipitated ERKs, and were highly responsive to exogenous insulin. In concordance, ERK total activity increased by 4-fold during the same period of growth and was further enhanced 2-fold by exogenous insulin. In weaning rats, ERKs were mainly located in membranes of villus cells and with less intensity in crypt cells. By contrast, p38 MAP kinase was unresponsive to insulin and was confined to nuclei. Administration to sucklings of PD 098059, a specific inhibitor of ERKs, not only inhibited the premature stimulation of sucrase, lactase, and maltase total activities in response to exogenous insulin, but also depressed the natural expression of these brush border membrane enzymes in the absence of insulin stimulation. In concordance, administration of SB 203580, a specific inhibitor of p38 MAP kinase, failed to inhibit both the response of brush border membrane hydrolases to insulin and their natural expression in the absence of insulin stimulation. We conclude that the ontogenic expression of brush border membrane hydrolases and their premature stimulation by insulin are regulated at least in part by the activation of p44/p42 ERKs but not by p38 MAP kinase.

ISSN:0031-3998    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Intracerebroventricular administration of recombinant adeno-associated virus (rAAV) encoding the rat leptin gene (rAAV-lep) to 24-d-old female and male rats suppressed postpubertal weight gain for extended periods by decreasing food consumption and adiposity, as reflected by lowered serum leptin, insulin, and FFA. Serum ghrelin levels were increased in young but not older rats. Central rAAV-lep therapy also increased energy expenditure through nonshivering thermogenesis in younger rats as shown by expression of uncoupling protein mRNA in brown adipose tissue. The sustained decrease in appetite seemingly resulted from attenuation of appetite-stimulating neuropeptide Y and enhancement of appetite-inhibiting melanocortin signalings in the hypothalamus. Neither the onset of pubertal sexual maturation nor reproductive cyclicity in adult female rats was affected by the sustained reduction in energy consumption and weight gain. These findings demonstrate that central leptin gene therapy in prepubertal rats is a novel therapy to control postpubertal weight gain, adiposity, and hyperinsulinemia for extended periods.

ISSN:0031-3998    

出版商:OVID    

年代:2002

数据来源: OVID