摘要:

Remarkable advances have recently elucidated the molecular genetic basis of inherited peripheral neuropathies. These studies revealed a novel mutational mechanism of a large DNA duplication as a cause for a common autosomal dominant demyelinating neuropathy. A peripheral nerve myelin gene,PMP22, located within the duplication is responsible for the demyelinating neuropathy by virtue of a gene dosage effect. The identification ofPMP22and other genes involved in myelinopathies demonstrate that these diseases represent a spectrum of disorders resulting from defects in myelin structure, maintenance, and/or formation.

ISSN:0031-3998    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Although evidence shows that victims of sudden infant death syndrome (SIDS) suffer repetitive episodes of hypoxemia, only subtle abnormalities have been found in their brains by light microscopy. The aim of the present study was to determine whether apoptosis, a form of cell death that can be triggered by hypoxemia and that leaves no scarring detectable by light microscopy, would be present in hypoxia-sensitive brain regions of SIDS victims. We looked for the presence of apoptosis with anin situend-labeling method that detects DNA fragmentation. We studied 29 SIDS victims who were age-matched to nine control cases. We found significant neuronal apoptosis in 79% of the SIDS cases: 55% of the cases positive in the hippocampus and 96% positive in the brainstem. Whereas the distribution of apoptosis in the hippocampus was in hypoxia-sensitive subregions, the distribution in the brainstem was mostly in dorsal nuclei, including those involved with sensation in the face and position of the head (nucleus of the spinal trigeminal tract and vestibular nuclei). The control cases showed no significant apoptosis in the hippocampus and a mild degree in the brainstem in three cases. Our results indicate the occurrence of an acute insult at least several hours before death, an insult from which the infants had apparently recuperated. This suggests that SIDS victims suffered repeated apoptosis resulting in significant neuronal damage and, thus, functional loss in key brain regions. The involvement of specific nuclei in the brainstem may be linked to the fact that prone sleeping is a significant risk factor for SIDS. Enhanced neuronal death by apoptosis may thus have major implications for understanding the sequence of events leading to SIDS.

ISSN:0031-3998    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

We investigated whether the changes detectable with magnetic resonance imaging techniques during and after an episode of cerebral hypoxia-ischemia differ in immature and older brain. Diffusion weighted (DW) and T2-weighted (T2W) images were repeatedly acquired before, during, and after an episode of cerebral hypoxia-ischemia (unilateral carotid artery occlusion plus hypoxia) in 2- and 4-wk-old rats lightly anesthetized with isoflurane. Areas of increased brightness were detected in DW images from both 2- and 4-wk-old rats by 10-20 min after the start of hypoxia. These hyperintense areas increased during hypoxia, comprising 60.8 ± 4.9% and 30.5 ± 2.7% of the brain image at the level of the thalamus in 2-wk-old and 4-wk-old animals, respectively (p< 0.003). Hyperintense areas (e.g.27.0 ± 8.3%) also appeared in T2W images during hypoxia-ischemia in 2-wk-old animals, but these did not occur in 4-wk-old animals (p< 0.02). This observation was reflected in T2, which increased during hypoxia-ischemia in the 2-wk-old but not the 4-wk-old group. By 60 min after the termination of hypoxia-ischemia in either age group, areas of hyperintensity resolved and then reappeared 24 h later on both DW and T2W images. Thus, irrespective of age, magnetic resonance imaging changes during transient hypoxia-ischemia generally recover with a delayed or secondary increase in DW and T2W hyperintensity hours later. Immature brain differs from older brain primarily with respect to some combination of hypoxic/ischemic cellular or biochemical changes, that are detectable as increases in T2within 2-wk-old but not 4-wk-old animals.

ISSN:0031-3998    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Mice with mucopolysaccharidosis type VII (MPS VII) are devoid of β-glucuronidase and accumulate glycosaminoglycans in lysosomes resulting in bone dysplasia, learning disabilities, and decreased mobility. MPS VII males do not breed and, while MPS VII females occasionally mate with heterozygous males, they do not maintain their young postnatally. Heterozygous matings produce less than 25% MPS VII offspring, but until now it was unclear whether this results from prenatal or postnatal losses. The administration of recombinant β-glucuronidase from birth significantly reduces glycosaminoglycan storage in most tissues, increases life span, and improves the animal's cognitive ability and mobility. To determine whether reproductive failure is corrected by such therapy, male and female MPS VII mice were injected with enzyme at weekly intervals from birth to 5 wk of age (6xinj). Enzyme-replaced MPS VII mice bred when mated together. The 6xinj MPS VII males mated repeatedly until they were killed 135 d postinjection. All mated 6xinj MPS VII females gave birth to two litters, but maintained few of their young. Selective loss of MPS VII offspring was observed in matings between heterozygotes. Analysis of 379 preterm fetuses from heterozygous matings showed a frequency of 24.6% MPS VII pups, indicating that the decreased number of MPS VII pups produced by mating heterozygotes results from postnatal losses. The ovaries of young adult MPS VII mice have follicles and corpora lutea, and the testes generate sperm. Results suggest that the reproductive failure in MPS VII mice is related to impaired mobility and/or impaired cognitive function, and enzyme replacement restores mating capacity.

ISSN:0031-3998    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Mutations in theWT1gene causing Wilms tumors were first reported in WAGR syndrome (Wilms tumor, Aniridia, Genitourinary malformation, mental Retardation) and Denys Drash syndrome (pseudohermaphroditism, Wilms tumor, nephropathy), but only in a few patients with hypospadias and cryptorchidism without other signs of Denys Drash (DDS) or WAGR syndromeWT1mutations were identified. We report a boy, who was born in 1989 with hypospadias and bilateral cryptorchidism. Previous karyotyping and endocrine studies had ruled out any known cause of male pseudohermaphroditism. Subsequently, he developed a bilateral Wilms tumor, which was detected by palpation at the age of 15 months during a routine visit by the general pediatrician. Because of its extensive size, surgery and chemotherapy were needed for treatment. Analysis of theWT1gene was performed 5 y after diagnosis and revealed a C to T transition in one allele generating a stop codon at codon 362 and subsequently leading to a truncated protein with loss of its ability to bind to DNA. No signs of DDS or WAGR syndrome are present in the boy. The work up of this patient and the so far known few comparable cases from the literature lead to the conclusion that in newborns with severe urogenital malformations not due to known chromosomal or endocrine disorders mutational screening of theWT1gene should be performed, to evaluate the high risk of developing a Wilms tumor. We favor mutational screening in these patients as an easy tool for investigation, because in the future it will probably decrease the necessity of frequent control visits in patients without aWT1mutation.

ISSN:0031-3998    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Zinc (Zn) is an essential nutrient for growth, but little is known about Zn absorption, distribution, excretion, and retention in preterm infants. Nine infants with gestational age 32 ± 1 wk (mean ± SE), birth weight 1.44 ± 0.08 kg, postnatal age 14 ± 3 d, on Zn intake of 23 ± 3 µmol/kg per d via enteral feeding of preterm formula were studied. A stable Zn isotope (70Zn) was administered orally or i.v., and plasma, red blood cells, urine, and feces were sampled for up to 30 d. Samples were analyzed for Zn by inductively coupled plasma atomic emission spectrometry and for isotope enrichment by inductively coupled plasma mass spectrometry. Data were analyzed by compartmental analysis using the Simulation Analysis and Modeling program, and absorption, distribution, excretion, and retention were calculated. Absorption was 36 ± 5% or 7 ± 1 µmol/kg per d; distribution in plasma was 15 ± 1 µmol Zn/L and in RBC was 41 ± 4 µmol Zn/L; excretion in urine was 0.55 ± 0.03 µmol Zn/kg per d and in feces was 17 ± 3 µmol Zn/kg per d and retention was 5 ± 1 µmol/kg per d. Results show that healthy preterm infants with Zn intake of 23 µmol/kg per d and expected growth rates (>15 g/kg per d) absorb and retain Zn at rates comparable toin uteroaccretion. The values for absorption, distribution, and excretion by this population of healthy preterm infants provide a normal range for future studies, although further studies are required to determine endogenous excretion rates in healthy preterm infants. We speculate that these values can be used to determine whether Zn kinetics are abnormal in sick infants or in infants with slow growth.

ISSN:0031-3998    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

There are substantial alterations in fuel homeostasis immediately after birth. Leptin is a putative regulator of energy metabolism. Consequently, the aim of this study was to examine whether there are changes in circulating leptin concentrations during the early postnatal period. Umbilical cord mixed blood samples were taken at delivery, and a venous blood sample was obtained at 3 d of age from 38 healthy newborn infants (20 male, 18 female; gestational age 36.3 to 41.9 wk) for analysis of leptin concentration with radioimmunoassay. Cord plasma leptin concentration was 9.7 ± 5.2 µg/L (mean ± SD), with no gender difference between male (8.6 ± 4.6 µg/L) and female (10.9 ± 5.6 µg/L) infants. In male newborns, cord plasma leptin concentration correlated with arm circumference (r= 0.48,p< 0.05), and in female newborns with body mass index (r= 0.62,p< 0.01), thickness of the s.c. fat (r= 0.54,p< 0.05), and arm circumference (r= 0.72,p< 0.01). By the third postnatal day, plasma leptin decreased similarly in male (to 1.8 ± 0.4 µg/L,p< 0.001) and female (to 2.3 ± 0.8 µg/L,p< 0.001) infants, when there was a significant gender difference in leptin levels (p= 0.01). At 3 d of age, plasma leptin correlated with weight (r= 0.49,p< 0.05) and arm circumference (r= 0.49,p< 0.05) in female but not in male newborns. In conclusion, 1) circulating leptin already correlates with adiposity at birth in female but not in male newborn infants and 2) leptin decreases markedly in both genders by the third postnatal day, and the gender difference with higher leptin levels in females develops by that time. Thus, the postnatal decrease in plasma leptin concentration may be a physiologically feasible adaptation to profound alterations in fuel homeostasis during the first days of extrauterine life.

ISSN:0031-3998    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Total parenteral nutrition (TPN) causes intrahepatic cholestasis and membrane phospholipid changes. Fatty acid (FA) composition of bile and hepatocyte phospholipid is influenced by dietary FA composition. We hypothesized that altering FA composition of i.v. lipid emulsions modifies1) severity of TPN-induced cholestasis;2) hepatocyte membrane composition and function;3) bile flow and composition. Newborn piglets received either sow's milk, TPN with i.v. soybean oil or TPN with i.v. fish oil (FO). After 3 wk, basal and stimulated bile flow were measured after bolus injections of 20, 50, and 100 µmol/kg of taurocholate (TCA). Bile was analyzed for bile acids, cholesterol, phospholipids, and phospholipid-FA. Sinusoidal and canalicular membrane PL-FA, fluidity, and Na+/K+-ATPase were measured. Although the soybean oil-fed animals developed cholestasis, the FO and milk group had similar liver and serum bilirubin. Basal and stimulated bile flow rates were impaired in the soybean oil but not in the FO group. Hepatocyte membrane FA composition reflected dietary FA. Changes in sinusoidal and canalicular membrane fluidity and sinusoidal Na+/K+-ATPase activity did not explain the effect of FO on TPN-induced cholestasis. Intravenous FO reduces TPN-induced cholestasis by unknown mechanisms.

ISSN:0031-3998    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

There is some evidence that fetuses of diabetic rats (FDR) are hypomineralized. To explore the pathogenic role of decreased maternal duodenal Ca absorption, fetal hypotrophy, and decreased placental calbindin-D9K, respectively, spontaneously diabetic rats fed a 1.0% Ca diet were compared with diabetic rats treated with 1,25-dihydroxyvitamin D3[1,25(OH)2D3] (15 ng/100 g) during week 3 of pregnancy, which restored duodenal calbindin-D9Kconcentrations to normal; with nondiabetic rats semistarved during week 3, which resulted in similar fetal hypertrophy; and with nondiabetic rats fed high cation diets (1.5% Ca-1.5% Sr and 1.5% Ca-3.5% Sr) during week 3, the latter of which repressed duodenal and placental calbindin-D9Ktoward concentrations measured in diabetic rats. In addition, fetal tibiae were studied histologically. Ca content was lower in 21.5-d-old FDR than in control fetuses. FDR had lower plasma osteocalcin (OC) levels and, on histomorphometry, increased hypertrophic cartilage width, indicating retarded bone maturation. Maternal 1,25(OH)2D3treatment did not change Ca content and hypertrophic cartilage width in FDR. Fetuses of semistarved rats had plasma OC levels and hypertrophic cartilage width comparable to those of control fetuses. Fetuses of rats fed the 1.5% Ca-3.5% Sr diet were more severely hypomineralized than FDR but had higher plasma OC than both FDR and control fetuses, compatible with fetal Ca deficiency. Whereas diabetic placentas showed weak but homogeneous staining of calbindin-D9Kin the labyrinth on immunohistology, degenerative zones were present in placentas of rats fed the 1.5% Ca-3.5% Sr diet. Thus, there is no mineralization defect in FDR caused by disturbed maternal duodenal Ca absorption or transplacental Ca transport, but a delay in bone maturation that is unexplained by their lower body weight.

ISSN:0031-3998    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Helicobacter pyloriinfection is a major cause of upper gastrointestinal disease throughout the world. Colonization begins in childhood, although little is known about its age of onset, rate, or mode of colonization. Our aim was to identify the age of acquisition ofH. pyloricolonization in Gambian children. A cohort of 248 Gambian children aged 3 to 45 months was studied at intervals of 3 months for 2 years, using the13C-urea breath test, specific IgM and specific IgG serology. The prevalence of positive breath tests rose from 19% at 3 months of age to 84% by age 30 months. Elevated specific IgG and IgM antibody levels were associated with positive breath tests, although there was discrepancy between breath test results and serology, particularly IgG serology, during the 1st year of life. Neither IgG nor IgM serology could be validated as reliable diagnostic tools for infantH. pyloricolonization compared with the13C-urea breath test. Reversion to negative breath test, in association with declining specific antibody levels, occurred in 48/248 (20%) of children. On the assumption that the13C-urea breath test is a reliable index ofH. pyloricolonization, we conclude that the infection is extremely common from an early age in Gambian children. Transient colonization may occur. Previous studies relying on serodiagnosis may have significantly underestimated the true early prevalence of colonization in the developing world, where the target age for intervention studies is probably early infancy.

ISSN:0031-3998    

出版商:OVID    

年代:1999

数据来源: OVID