ISSN:0031-3998    

出版商:OVID    

年代:1999

数据来源: OVID

ISSN:0031-3998    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Msx and Dlx family transcription factors are key elements of craniofacial development and act in specific combinations with growth factors to control the position and shape of various skeletal structures in mice. In humans, the mutations of MSX and DLX genes are associated with specific syndromes, such as tooth agenesis, craniosynostosis, and tricho-dento-osseous syndrome. To establish some relationships between those reported human syndromes, previous experimental data in mice, and the expression patterns of MSX and DLX homeogenes in the human dentition, we investigated MSX-2, DLX-5, and DLX-7 expression patterns and compared them in orofacial tissues of 7.5- to 9-wk-old human embryos by usingin situhybridization. Our data showed that MSX-2 was strongly expressed in the progenitor cells of human orofacial skeletal structures, including mandible and maxilla bones, Meckel’s cartilage, and tooth germs, as shown for DLX-5. DLX-7 expression was restricted to the vestibular lamina and, later on, to the vestibular part of dental epithelium. The comparison of MSX-2, DLX-5, and DLX-7 expression patterns during the early stages of development of different human tooth types showed the existence of spatially ordered sequences of homeogene expression along the vestibular/lingual axis of dental epithelium. The expression of MSX-2 in enamel knot, as well as the coincident expression of MSX-2, DLX-5, and DLX-7 in a restricted vestibular area of dental epithelium, suggests the existence of various organizing centers involved in the control of human tooth morphogenesis.

ISSN:0031-3998    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Transforming growth factor-&bgr;2 (TGF-&bgr;2) levels in rat milk are high in early lactation, whereas endogenous TGF-&bgr;1 expression in the neonatal gut increases toward midweaning. Three types of transmembrane TGF-&bgr; receptors have been identified in mammals. The receptor III (or betaglycan) binds and presents TGF-&bgr;1 or &bgr;2 to receptor II. Receptor I then interacts with receptor II, forming a signaling receptor complex, and propagates the signal. To determine whether TGF-&bgr; receptor expression in the gut is also developmentally regulated, the present study assessed ontogeny of TGF-&bgr; receptor expression in the postnatal rat small intestine. Jejunum and ileum tissues from rat pups at d 3, 10, 14, 21, and 28 of age were collected. Cryostat sections were stained with antibodies against TGF-&bgr; receptors I, II, and III, and various cell markers by immunofluorescence. In both regions, receptor I staining was seen on apical and basolateral membranes of the villus and crypt epithelium at all ages, and staining on the apical membrane increased with age; receptor II was predominantly expressed in the crypt, and staining on the villi appeared after d 10; receptor III was distributed throughout the mucosa at early ages but diminished from the epithelium postweaning by d 28. T cells, B cells, and dendritic cells in the lamina propria expressed TGF-&bgr; receptor III but lacked expression of receptor I and II. The pattern of TGF-&bgr; receptor expression changes with age in a manner that may reflect the change in ligand from TGF-&bgr;2 (milk-derived) to TGF-&bgr;1 (endogenously produced).

ISSN:0031-3998    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

In pathogenesis of celiac disease, the significance of prolamin peptide interactions with enterocytes is controversial. Changes in cellular metabolism induced by gliadin peptides, as well as uptake and presentation by enterocytes, are discussed. We analyzed peptide binding to enterocytic membranes as a potential key event. Binding capacities of brush border membranes isolated from small intestinal biopsies of untreated (n= 49) and treated celiac patients on a gluten-free diet (n= 30), as well as control subjects (n= 43), were measured with a dot blot chemiluminescence assay. Synthetic gliadin peptides comprising amino acid position 8–19 (G XIV) and 30–41 (G XI) of &agr;-gliadins, a peptic-tryptic digest of gliadin (PT-GLI), and a synthetic zein peptide were used. Comparing treated celiac patients with controls, we observed significantly enhanced membrane-binding of PT-GLI [mean 122.4 densitometric units/&mgr;g (95% confidence interval 116.0–128.9)vs108.9 (102.1–115.7)] and of zein peptide [50.2 (38.4–61.9)vs28.8 (13.4–44.2)], but only slightly increased binding of the synthetic gliadin peptides G XIV [65.5 (60.6–70.5)vs62.4 (56.3–68.5) and G XI [75.2 (69.8–80.6)vs65.9 (55.2–76.5)]. Independent of patient group, membrane-binding capacities for celiac-active gliadin peptides exceeded those of the zein peptide. Thus, interaction of gliadin peptides with the apical enterocytic membrane was not found exclusively in celiac disease. Furthermore, increased binding capacities in treated celiac disease were not confined to celiac-active peptides. Quantitative differences in gliadin peptide binding as a primary characteristic in celiac disease might contribute to pathogenetic effects exerted on small intestinal epithelial cells.

ISSN:0031-3998    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Holocarboxylase synthetase (HCS) deficiency is a metabolic disorder that causes a biotin-responsive multiple carboxylase deficiency. We analyzed the kinetic properties of seven mutant HCS proteins. Two of these enzymes harbored mutations within the putative biotin-binding region of HCS and showed elevatedKmvalues for biotin compared with that of the wild-type form (Kmmutant; Gly581Ser: 45 times, delThr610: 3 times). The remaining five mutations (Arg183Pro, Leu216Arg, Leu237Pro, Val333Glu, and Val363Asp) were located outside the biotin-binding region. The enzymes containing these mutations showed normal or lowKmvalues for biotin (non-Kmmutant). Symptoms of patients who have the non-Kmmutants, as well as those of patients who have theKmmutants, responded to biotin therapy. This is probably because theKmvalue for biotin of normal HCS is higher than the physiologic concentration of biotin in human cells. TheVmaxvalues of all mutant HCS proteins were considerably decreased, but to a variable degree. The responsiveness to biotin supplementation of propionyl-CoA carboxylase activity in cultured cells bearing the mutations correlated well with the degree of reduction in theVmaxof HCS. Patients who have mutant HCS proteins with lowerVmaxshowed poorer clinical and biochemical responses to biotin therapy. These observations suggest that the reduction ofVmaxis an essential factor for pathophysiology and prognosis of HCS deficiency under treatment with large amounts of biotin. The determination of HCS genotype can be valuable for characterizing the clinical phenotype in HCS deficient patients.

ISSN:0031-3998    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Barbiturates are known to inhibit glucose transport mediated by the facilitative sugar transporter GLUT1. We have studied such inhibition in children with GLUT1-deficiency. Zero-trans influx of14C-labeled 3-O-methyl glucose (3OMG) into erythrocytes of patients (n= 3) was 35% of controls (n= 6). Preincubation with 10 mM phenobarbital or pentobarbital reduced patients’ 3OMG influx to 17%. In patients and controls, preincubation with barbiturates significantly decreasedVmaxin a dose-dependent manner (for pentobarbital, IC50= 0.84 mM, patient 2). The apparentKmin individuals remained largely unchanged. Three-OMG influx without preincubation resulted in a stronger inhibition at lower barbiturate concentrations. The patients’ data are discussed in the light of individual missense mutations (patient 1: R126L and K256V; patient 2: T310I; patient 3: S66F) in the GLUT1 gene. In conclusion, in controls and patients with GLUT1-deficiency barbiturates interact with GLUT1, lowering its intrinsic activity. The use of barbiturates in this condition for anesthesia or as anticonvulsants could therefore potentially aggravate the existing glucose transport defect and may put these patients at increased risk.

ISSN:0031-3998    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

We recently found that postzygoticde novomutations occur at the expected high rate of an X-linked recessive mutation in androgen insensitivity syndrome. The resulting somatic mosaicism can be an important molecular determinant ofin vivoandrogen action caused by expression of the wild-type androgen receptor (AR). However, the clinical relevance of this previously underestimated genetic condition in androgen insensitivity syndrome has not been investigated in detail as yet. Here, we present the clinical and molecular spectrum of somatic mosaicism considering all five patients with mosaic androgen insensitivity syndrome, whom we have identified since 1993: Patient 1 (predominantly female, clitoromegaly), 172 TTA(Leu)/TGA(Stop); patient 2 (ambiguous), 596 GCC(Ala)/ACC(Thr); patient 3 (ambiguous), 733 CAG(Gln)/CAT(His); patient 4 (completely female), 774 CGC(Arg)/TGC (Cys); and patient 5 (ambiguous), 866 GTG(Val)/ATG(Met). Serum sex hormone binding globulin response to stanozolol, usually correlating well within vivoAR function, was inconclusive for assessment of the phenotypes in all tested mosaic individuals. An unexpectedly strong virilization occurred in patients 1, 3, and 5 compared with phenotypes as published with corresponding inherited mutations and compared with the markedly impaired transactivation caused by the mutant ARs in cotransfection experiments. Only the prepubertal virilization of patients 2 and 4 matched appropriately with transactivation studies (patient 4) or the literature (patients 2 and 4). However, partial pubertal virilization in patient 4 caused by increasing serum androgens and subsequent activation of the wild-type AR could not be excluded. We conclude that somatic mosaicism is of particular clinical relevance in androgen insensitivity syndrome. The possibility of functionally relevant expression of the wild-type AR needs to be considered in all mosaic individuals, and treatment should be adjusted accordingly.

ISSN:0031-3998    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

We are the first to report clinical characteristics and circulatory and catecholamine responses to postural change in 44 children with instantaneous orthostatic hypotension (INOH). The symptoms include chronic fatigue, orthostatic dizziness, weakness, sleep disturbance, syncope or near syncope, headache, and loss of appetite. We divided the patients into two groups: group I (30 patients) had either a recovery time for mean arterial pressure of >25 s or a recovery time of >20 s with a 60% or greater decrease in mean arterial pressure at the initial decrease; group II (14 patients) had a prolonged reduction in systolic arterial pressure of >15% during the later stage of standing (3–7 min) in addition to the criteria for group I. INOH was characterized by a marked reduction in blood pressure at the initial decrease (mean, −55/−27 mm Hg systolic/diastolic). Delayed recovery time of >60 s was found in 21 of 44 patients and orthostatic tachycardia (>35 beats per minute) in 20 of 44. Plasma noradrenaline responses were significantly lower in group I and II than in controls at 1 min of standing and were lower in group II at 5 min of standing. These results suggest that mechanisms responsible for INOH may depend on insufficient sympathetic activation during standing, possibly due to centrally mediated sympathetic inhibition, thus causing impairment of quality of life including school absenteeism. INOH is an important pathologic condition in children with complaints of orthostatic intolerance and can be an unrecognized cause of chronic fatigue. This condition can be identified by using a noninvasive beat-to-beat continuous blood pressure monitoring system.

ISSN:0031-3998    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Obesity in adults is associated with an increased mortality rate from various diseases. Childhood overweight or obesity may persist into adulthood, and for this reason it is important to identify such children at risk. The data were taken from a larger longitudinal growth study of 3650 full-term and healthy Swedish babies followed from birth to 18 y of age. Body mass index (BMI) was used to estimate (during the pediatric years) the risk of obesity at 18 y of age. A probability chart for becoming overweight (>25 kg/m2) by 18 y of age was constructed, For example, in girls, a BMI of 16 kg/m2at 4 y of age is associated with a 20% risk of attaining a BMI value over 25 kg/m2at 18 y, and in boys at 4 y of age, a BMI of 19 kg/m2leads to a 60% risk that they will have a BMI value over 25 kg/m2at 18 y. The probability risk charts for adult overweight developed here is the first one presented. They provide an easy and novel instrument to use to identify those children who are at high risk of becoming obese adults, so that they may have clinical intervention at younger ages.

ISSN:0031-3998    

出版商:OVID    

年代:1999

数据来源: OVID