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Growth Retardation (growth + retardation)
Kinds of Growth Retardation Selected AbstractsChildren of Helicobacter pylori -infected Dyspeptic Mothers are Predisposed to H. pylori Acquisition with Subsequent Iron Deficiency and Growth RetardationHELICOBACTER, Issue 3 2005Yao-Jong Yang Abstract Background., We tested whether Helicobacter pylori -infected dyspeptic mothers had a higher rate of H. pylori infection in their children, and whether such H. pylori -infected children were predisposed to iron deficiency or growth retardation. Materials and methods., A total of 163 children from 106 dyspeptic mothers (58 with and 48 without H. pylori infection) were enrolled to evaluate body weight, height, hemoglobin, serum ferritin, and H. pylori infection using the 13C-urea breath test. A questionnaire was used to evaluate demographic factors of each child. Results., The rate of H. pylori infection in children with H. pylori -infected dyspeptic mothers was higher than that of children with noninfected mothers (20.5% vs. 5.3%; p < .01, OR: 4.6, 95% CI: 1.5,14.2). The rate of H. pylori infection in children elevated as the number of their H. pylori -infected siblings increased (p < .01). For children below 10 years of age, H. pylori infection was closely related to low serum ferritin and body weight growth (p < .05). Conclusion., The children of H. pylori -infected dyspeptic mothers had an increased risk for such infection. The risk further increased once their siblings were infected. H. pylori infection in pre-adolescent children may determine iron deficiency and growth retardation. [source] Selenium Deficiency-Induced Growth Retardation Is Associated with an Impaired Bone Metabolism and OsteopeniaJOURNAL OF BONE AND MINERAL RESEARCH, Issue 8 2001Rodrigo Moreno-Reyes Abstract Although the importance of selenium for bone metabolism is unknown, some clinical conditions such as Kashin-Beck osteoarthropathy have been associated with selenium deficiency. Although selenium deficiency induces growth retardation in rats, it has not been established whether this growth inhibition is associated with changes in bone metabolism. We investigated the effect of selenium deficiency on bone metabolism in growing male rats fed a selenium-deficient diet for two generations (Se,). In Se, rats, erythrocyte glutathione peroxidase activity and plasma selenium concentration were strongly reduced compared with pair-fed selenium-adequate rats (Se+). Weight and tail length were reduced by 31% and 13% in the Se, rats, respectively (p < 0.001). The Se, diet was associated with a 68% reduction of pituitary growth hormone (GH; p = 0.01) and a 50% reduction of plasma insulin-like growth factor I (IGF-I; p < 0.001). Plasma calcium was lower and urinary calcium concentration was greater in Se, rats. This group had a 2-fold increase in parathyroid hormone (PTH) and 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] in plasma. Plasma osteocalcin and urinary deoxypyridoline were reduced by 25% and 57% in the Se, rats (p < 0.001). Selenium deficiency resulted in a 23% and 21% reduction in bone mineral density (BMD) of the femur and tibia (p < 0.001) and this effect persisted after adjustment for weight in a linear regression model. A 43% reduction in trabecular bone volume of the femoral metaphysis (p < 0.001) was found in Se, rats. This experimental study shows that growth retardation induced by selenium deficiency is associated with impaired bone metabolism and osteopenia in second-generation selenium-deficient rats. [source] Pre-emptive renal transplantation in childrenINTERNATIONAL JOURNAL OF UROLOGY, Issue 5 2001Hiroshi Harada Abstract Background: Renal transplantation is a definitive therapeutic modality in end-stage renal disease (ESRD). Most ESRD patients in Japan experience dialysis prior to renal transplantation. The present study was undertaken to examine the usefulness of pre-emptive renal transplantation (PET). Methods: Between 1987 and 1998, 255 renal transplantations were carried out by the authors. Among those consecutive cases, 10 were cases of PET. In nine pediatric cases, demographics, graft and patient survival, height growth and benefits from successful transplantation were studied and compared with age-matched dialyzed transplantation controls. Results: All transplantation was living-related. There was a disparity of causes of ESRD between the two groups. In PET, acquired renal deterioration due to a congenital lower urinary tract disorder was the major cause. Graft and patient prognosis was favorable in both groups. Growth retardation in PET patients under 15 years of age was significantly less apparent at the time of transplantation and after 3 years compared to the control. The benefits from transplantation were different in the two groups. Most PET patients felt an improvement of their physical condition; however, all of the control patients felt that the major boon was the freedom from the restriction of the daily diet and time for dialysis. Conclusion: In pediatric renal transplantation, short-term preceding dialysis does not have a detrimental effect, but PET could benefit ESRD patients by maintaining their quality of life. Moreover, PET minimizes the production of renal dwarfism in prepubertal children. Thus, PET should be taken into consideration in the choice of renal replacement therapy. [source] Critical analysis of potential body temperature confounders on neurochemical endpoints caused by direct dosing and maternal separation in neonatal mice: a study of bioallethrin and deltamethrin interactions with temperature on brain muscarinic receptorsJOURNAL OF APPLIED TOXICOLOGY, Issue 1 2003Jürgen Pauluhn Abstract The present investigation was conducted to understand better possible confounding factors caused by direct dosing of neonatal mice during the pre-weaning developmental period. By direct dosing, pups might encounter thermal challenges when temporarily removed from their ,natural habitat'. Typically, this leads to a cold environment and food deprivation (impaired lactation) and modulation of the toxic potency of the substance administered. Growth retardation as a consequence of such behavioural changes in pups makes it increasingly difficult to differentiate specific from non-specific mechanisms. Neonatal NMRI mice were dosed daily by gavage (0.7 mg kg,1 body wt.) from postnatal day (PND) 10,16 with S -bioallethrin, deltamethrin or the vehicle. Then the pups, including their non-treated foster dams, were subjected temporarily for 6 h day to a hypo-, normo- or hyperthermic environment, which was followed by normal housing. The measured temperatures in the environmental chambers were ca. 21, 25 and 30°C, respectively. Thus, temperatures in the hypo- and normothermic groups are comparable to the temperatures commonly present in testing laboratories, whereas the hyperthermic condition is that temperature typically present in the ,natural habitat' of pups. A deviation from the normal behaviour of both pups and dams was observed in the hypo- and normothermic groups. In these groups the rectal temperatures of pups were markedly decreased, especially in the early phase of the study (PND 10,12). Neonates that received either test substance displayed changes in body weights and brain weights at terminal sacrifice (PND 17) when subjected temporarily to a non-physiological environment. An enormous influence of environmental temperature on the density of muscarinic receptors in the crude synaptosomal fraction of the cerebral cortex was ascertained. In summary, these results demonstrate that the direct dosing of thermolabile neonatal mice by gavage is subject to significant artefacts that render the interpretation of findings from such studies difficult. It appears that if direct dosing of neonatal pups is mandated, and inhalation is a relevant route of exposure, the combined inhalation exposure of dams with their litters is an alternative procedure that does not cause disruption of the ,natural habitat' of pups. However, owing to their higher ventilation, under such conditions the pups may receive dosages at least double those of the dams. Copyright © 2003 John Wiley & Sons, Ltd. [source] Intracranial germinoma: A rare but important differential diagnosis in children with growth retardationACTA PAEDIATRICA, Issue 3 2006Sven Gottschling Abstract Aim: Intracranial germinoma is a rare malignant tumour in childhood with an excellent prognosis under adequate therapy. Finding the right diagnosis at an early stage is difficult because of the slow-growing tumour and the resulting lack of clinical symptoms. Methods: Our patients with histologically secured germinoma were retrospectively assessed concerning growth retardation, pituitary hormone status, magnetic resonance imaging scan results and clinical symptoms to find out whether there is a leading parameter. Results: In all our patients, the leading symptom was growth retardation of at least 2 y before being diagnosed. Conclusion: Growth retardation seems to be a very early sign of germinoma in the suprasellar region. Therefore, early neuroradiological imaging combined with pituitary hormone status should be considered in every paediatric patient with a history of secondary growth retardation. [source] Molecular and clinical consequences of novel mutations in the arylsulfatase A geneCLINICAL GENETICS, Issue 1 2009ugowska Metachromatic leukodystrophy (MLD), a severe neurodegenerative metabolic disorder, is caused by deficient activity of arylsulfatase A (ARSA; EC 3.1.6.8), which leads to a progressive demyelinating process in central and peripheral nervous systems. In this study, a DNA sequence analysis was performed on six Polish patients with different types of MLD. Six novel mutations were identified: one nonsense (p.R114X), three missense (p.G122C, p.G293C, p.C493F) and two frameshift mutations (g.445_446dupG and g.2590_2591dupC). Substitutions p.G293C and p.C493F and duplication g.445_446dupG caused a severe reduction of enzyme activity in transient transfection experiments on mammalian cells (less than 1% of wild-type (WT) ARSA activity). Duplication 2590_2591dupC preserved low-residual ARSA activity (10% of WT ARSA). In summary, the novel MLD-causing mutations in the exons 2, 5 and even in 8 of the ARSA gene described here can be classified as severe type 0, leading in homozygosity to the late infantile form MLD. Growth retardation, delayed motor development, gait disturbances, tonic,clonic seizures and non-epileptic muscle spasms were the first onset symptoms in patients with late infantile form of MLD. In individual with juvenile type MLD gait disturbances evidenced the onset of the disease, while in a patient with late juvenile MLD, difficulties at school were displayed. [source] Abnormal fetal aortic velocity waveform and postnatal growthACTA PAEDIATRICA, Issue 11 2000D Ley Postnatal growth from birth up to 7 y of age was evaluated in 151 children with varying degrees of intrauterine growth retardation who were previously examined in their intrauterine life with Doppler velocimetry of the thoracic descending aorta. The children with abnormal fetal aortic blood flow class (BFC), of which 39/46 (85%) had a birthweight 2 SD below the mean of the population, were lean at birth and had a high rate of catch-up growth in weight and length during the first 3 and 6 mo, respectively. After the initial phases of rapid catch-up in weight and length, mean values of SD scores for weight and height remained relatively unchanged up until 2 y of age, thereafter increasing gradually up to 7 y of age, leaving 4/46 (8%) and 4/46 (8%) below ,2 SD for weight and height, respectively. The pattern of changes in length/height and weight over time did not differ between those infants with abnormal BFC and those with normal BFC. The abnormal fetal aortic waveform was not related to rate of early catch-up growth or to height or weight at 7 y of age after adjustment for deviation in growth at birth. The magnitude of deficit in weight and length at birth was more predictive of subsequent growth. [source] The mother-offspring dyad and the immune systemACTA PAEDIATRICA, Issue 3 2000LÅ Hanson A. The mother and the fetus. The mother's immune system reacts against the fetus and there is therefore a risk of destruction of or damage to the fetus. We are now beginning to understand some of the mechanisms that protect the fetus, but, when these are defective, intrauterine growth retardation or abortions may ensue. However, the cytokines of this maternal immune response to the fetus also monitor different phases of pregnancy, starting with effects on the ovarium and involving preparation of the decidua for the implantation of the fertilized egg, the growth of the trophoblasts, the production of hormones important for the pregnancy and finally of the prostaglandins that induce delivery. B. The mother and the child. Human milk contains anti-idiotypic antibodies which after transfer to the offspring are capable of enhancing antibody responses. Human milk contains numerous leucocytes especially during early lactation. There is increasing evidence that milk lymphocytes are taken up by the breastfed infant, which seems to have become tolerant to maternal HLA. Breastfeeding mothers are therefore good donors of renal transplants to their breastfed offspring in adult age, too. Conclusion: It is suggested that the milk lymphocytes may be taken up by the offspring and that immunological information is thereby carried over from the mother. This mechanism may explain why breastfeeding seems to confer enhanced protection against infections also some years after the termination of breastfeeding. [source] The conservative treatment of pediatric mandibular fracture with prefabricated surgical splint: a case reportDENTAL TRAUMATOLOGY, Issue 4 2007Ceyda Kocabay Abstract,,, The use of rigid fixation in children is controversial and may cause growth retardation along cranial suture lines. Intermaxillary fixation for mandibular fractures should be used cautiously as bony ankylosis in the temporomandibular joint (TMJ) and trismus may develop. The high osteogenic potential of the pediatric mandible allows non-surgical management to be successful in younger patients with conservative approaches. In this case, successful conservative treatment of mandibular fracture of a 3-year-old patient is presented. [source] Impaired lactation in mice expressing dominant-negative FADD in mammary epitheliumDEVELOPMENTAL DYNAMICS, Issue 4 2009Mark Shackleton Abstract The Fas-associated death domain (FADD/Mort1) adaptor protein was originally identified as a key mediator of apoptosis, although pleiotropic functions for FADD have also been reported. FADD-mediated tumoricidal effects have been described in breast cancer cells; however, its physiological role in normal mammary gland epithelium is not well understood. To determine the role of FADD signaling during mammary gland development, we generated transgenic mice overexpressing dominant-negative FADD (DN-FADD) in mammary epithelium, using the steroid responsive mouse mammary tumor virus promoter. Transgenic mice exhibited a perturbation in lactation resulting in impaired milk production and pup growth retardation. Reduced expansion of alveoli was evident during early lactation with extensive shedding of luminal alveolar cells. Significantly more TUNEL (terminal deoxynucleotidyl transferase,mediated deoxyuridinetriphosphate nick end-labeling)-positive cells were present at this time point and a subsequent increase in bromodeoxyuridine-positive cells was observed. These findings suggest a role for FADD in maintaining the survival of mammary secretory alveolar cells after the establishment of lactation. Developmental Dynamics 238:1010,1016, 2009. © 2009 Wiley-Liss, Inc. [source] Nuclear receptor NR5A2 is required for proper primitive streak morphogenesisDEVELOPMENTAL DYNAMICS, Issue 12 2006Cassandre Labelle-Dumais Abstract NR5A2, also known as liver receptor homologue 1 (LRH-1) and fetoprotein transcription factor (FTF), is an orphan nuclear receptor involved in the regulation of cholesterol metabolism and steroidogenesis in the adult. NR5A2 was also shown to be expressed during early mouse embryogenesis. Consistent with its early expression pattern, a targeted disruption of this gene leads to embryonic lethality around the gastrulation period. To characterize the embryonic phenotype resulting from NR5A2 loss of function, we undertook morphological and marker gene analyses and showed that NR5A2,/, embryos display growth retardation, epiblast disorganization, a mild embryonic,extraembryonic constriction, as well as abnormal thickening of the proximo-posterior epiblast. We demonstrated that, although initial specification of the anterior,posterior axis occurred in the absence of NR5A2, primitive streak formation was impaired and neither embryonic nor extraembryonic mesoderm was generated. Moreover, although the visceral endoderm does not show major morphological abnormalities in NR5A2,/, embryos, a decrease in the expression level of HNF4 and GATA4 was observed. Aggregation experiments demonstrated that, in the presence of wild-type tetraploid cells, NR5A2 mutant cells in the epiblast are capable of undergoing normal gastrulation. Therefore, our results suggest a requirement for NR5A2 in extraembryonic tissues and identify a novel role of this gene in proper primitive streak morphogenesis. Developmental Dynamics 235:3359,3369, 2006. © 2006 Wiley-Liss, Inc. [source] Growth defect in Grg5 null mice is associated with reduced Ihh signaling in growth platesDEVELOPMENTAL DYNAMICS, Issue 1 2002Wen-Fang Wang Abstract Gene-targeted disruption of Grg5, a mouse homologue of Drosophila groucho (gro), results in postnatal growth retardation in mice. The growth defect, most striking in approximately half of the Grg5 null mice, occurs during the first 4,5 weeks of age, but most mice recover retarded growth later. We used the nonlinear mixed-effects model to fit the growth data of wild-type, heterozygous, and Grg5 null mice. On the basis of preliminary evidence suggesting an interaction between Grg5 and the transcription factor Cbfa1/Runx2, critical for skeletal development, we further investigated the skeleton in the mice. A long bone growth plate defect was identified, which included shorter zones of proliferative and hypertrophic chondrocytes and decreased trabecular bone formation. This decreased trabecular bone formation is likely caused by a reduced recruitment of osteoblasts into the growth plate region of Grg5 null mice. Like the growth defect, the growth plate and trabecular bone abnormality improved as the mice grew older. The growth plate defect was associated with reduced Indian hedgehog expression and signaling. We suggest that Grg5, a transcriptional coregulator, modulates the activities of transcription factors, such as Cbfa1/Runx2 in vivo to affect Ihh expression and the function of long bone growth plates. © 2002 Wiley-Liss, Inc. [source] Impact of gestational distress and growth retardation on emotional problems in offspringACTA PSYCHIATRICA SCANDINAVICA, Issue 2 2007Ruth Brand Flu No abstract is available for this article. [source] Manometric study in Kearns,Sayre syndromeDISEASES OF THE ESOPHAGUS, Issue 1 2001K. H. Katsanos Although swallowing difficulties have been described in patients with Kearns,Sayre syndrome (KSS), the spectrum of manometric characteristics of dysphagia is not yet well known. Moreover, it is conceivable that a combination of various degrees of swallowing difficulties with different patterns in manometric studies exist, each playing a major role in the prognosis, natural history, and quality of life of KSS patients. An 18-year-old girl diagnosed at the age of 5 years with KSS (muscle biopsy) was admitted to our department with an upper respiratory tract infection and dysphagia. Clinical examination revealed growth retardation, external ophthalmoplegia, pigmentary retinopathy, impaired hearing, and ataxia. An electrocardiogram revealed cardiac conduction defects (long Q-T), and brain magnetic resonance imaging showed abnormalities in the cerebellar hemispheres. A manometric and motility study for dysphagia was conducted and the pharynx and upper esophageal sphincter (UES) resting pressures were similar to control group values, but the swallowing peak contraction pressure of the pharynx and the closing pressure of the UES were very low and could not promote effective peristaltic waves. Relaxation and coordination of the UES were not affected although pharyngeal and upper esophagus peristaltic waves proved to be very low and, consequently, were practically ineffective. The patient was started on treatment comprising a diet rich in potassium, magnesium, and calcium, and oral administration of vitamin D and co-enzyme Q10 100 mg daily; she was discharged 6 days later with apparent clinical improvement. [source] Phenotypic diagnosis of dwarfism in six Friesian horsesEQUINE VETERINARY JOURNAL, Issue 3 2008W. BACK Summary An extreme form of abnormal development, dwarfism, is common in man and some animals, but has not been officially reported in horses. Within the Friesian horse breed, congenital dwarfism has been recognised for many years, but no detailed report exists on its phenotype. The most salient feature of the dwarf syndrome is the physeal growth retardation in both limbs and ribs. Affected animals have approximately 25% shorter fore- and hindlimbs and approximately 50% reduced bodyweight. Post natal growth is still possible in these animals, albeit at a slower rate: the head and back grow faster than the limbs and ribs leading to the characteristic disproportional growth disturbance. Thus, mature dwarfs exhibit a normal, but a relatively larger head conformation, a broader chest with narrowing at the costochondral junction, a disproportionally long back, abnormally short limbs, hyperextension of the fetlocks and narrow long-toed hooves. Furthermore, a dysplastic metaphysis of the distal metacarpus and metatarsus is radiographically evident. Microscopic analysis of the growth plates at the costochondral junction shows an irregular transition from cartilage to bone, and thickening and disturbed formation of chondrocyte columns, which is similar to findings in osteochondrodysplasia. [source] Effects of maternal smoking in pregnancy on prenatal brain development.EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 3 2007The Generation R Study Abstract Nicotine, as has been shown in animal studies, is a neuroteratogen, even in concentrations that do not cause growth retardation. In humans, there is only indirect evidence for negative influences of nicotine on brain development from studies on the association between maternal smoking in pregnancy and behavioural and cognitive development in the offspring. We investigated the associations of maternal smoking in pregnancy with foetal head growth characteristics in 7042 pregnant women. This study was embedded in the Generation R Study, a population-based prospective cohort study from foetal life until adulthood. Maternal smoking was assessed by questionnaires in early, mid- and late pregnancy. Head circumference, biparietal diameter, transcerebellar diameter and atrial width of lateral ventricles were repeatedly measured by ultrasound. When mothers continued to smoke during pregnancy, foetal head circumference showed a growth reduction of 0.13 mm [95% confidence interval (CI): ,0.18, ,0.09] per week compared to foetuses of mothers who never smoked during pregnancy. Biparietal diameter of foetuses with smoking mothers grew 0.04 mm (95% CI: ,0.05, ,0.02) less per week than that of foetuses of nonsmoking mothers. Atrial width of lateral ventricle was 0.12 mm (95% CI: ,0.22, ,0.02) smaller and transcerebellar diameter was 0.08 mm (95% CI: ,0.15, ,0.00) smaller if mothers smoked, but growth per week of these characteristics was not affected by maternal smoking in pregnancy. In conclusion, continuing to smoke during pregnancy leads to reduced growth of the foetal head. Further research should focus on the causal pathway from prenatal cigarette exposure via brain development to behavioural and cognitive functions. [source] Effects of spectrum modification on fatigue crack growthFATIGUE & FRACTURE OF ENGINEERING MATERIALS AND STRUCTURES, Issue 3 2010D. KUJAWSKI ABSTRACT The purpose of this study was to investigate experimentally the effects associated with modification of a loading spectrum recorded from P-3 a maritime aircraft on fatigue crack growth behaviour. The material is 2324-T39 Al alloy widely used in the aircraft industry. Experiments were conducted using the full spectrum and modified versions of it such as only ,positive' (no negative loads) or with reduced (clipped) high peaks. The results show that the compressive loads decrease fatigue life of the specimen by ,300%. Furthermore, by running tests with clipped peaks it was found that the fatigue life was shorten significantly due to reduction of crack growth retardation caused by highest tensile peaks. Multiple tests were conducted in order to establish a scatter in the experimental data under spectrum loads. [source] Functional dissection of two Arabidopsis PsbO proteinsFEBS JOURNAL, Issue 9 2005PsbO PsbO protein is an extrinsic subunit of photosystem II (PSII) and has been proposed to play a central role in stabilization of the catalytic manganese cluster. Arabidopsis thaliana has two psbO genes that express two PsbO proteins; PsbO1 and PsbO2. We reported previously that a mutant plant that lacked PsbO1 (psbo1) showed considerable growth retardation despite the presence of PsbO2 [Murakami, R., Ifuku, K., Takabayashi, A., Shikanai, T., Endo, T., and Sato, F. (2002) FEBS Lett523, 138,142]. In the present study, we characterized the functional differences between PsbO1 and PsbO2. We found that PsbO1 is the major isoform in the wild-type, and the amount of PsbO2 in psbo1 was significantly less than the total amount of PsbO in the wild-type. The amount of PsbO as well as the efficiency of PSII in psbo1 increased as the plants grew; howeVER, it neVER reached the total PsbO level observed in the wild-type, suggesting that the poor activity of PSII in psbo1 was caused by a shortage of PsbO. In addition, an in vitro reconstitution experiment using recombinant PsbOs and urea-washed PSII particles showed that oxygen evolution was better recoVERed by PsbO1 than by PsbO2. Further analysis using chimeric and mutated PsbOs suggested that the amino acid changes Val186,Ser, Leu246,Ile, and Val204,Ile could explain the functional difference between the two PsbOs. Therefore we concluded that both the lower expression level and the inferior functionality of PsbO2 are responsible for the phenotype observed in psbo1. [source] Accumulation of multiple forms of lamin A with down-regulation of FACE-1 suppresses growth in senescent human cellsGENES TO CELLS, Issue 3 2007Ryo Ukekawa 5-Bromodeoxyuridine (BrdU) clearly induces a senescence-like phenomenon in every cell type. Proteome analysis revealed that lamin A and C were most highly increased in the nuclei of HeLa cells upon addition of BrdU. Immunoblot analysis also revealed marked accumulation of nuclear prelamin A. Consistently, farnesylated-proteins converting enzyme 1 (FACE-1) was markedly down-regulated in the same cells. Similar phenomena were also observed in normal human fibroblasts undergoing replicative senescence. Immunochemical analysis confirmed the above results. Lamin A is a major component of lamina and responsible for several genetic diseases. Thus, we ectopically expressed a wild-type, a mature type and a premature type of lamin in HeLa cells. All of these forms similarly inhibited colony formation and delayed cell cycle progression mainly through G2 phase. These results suggest that a change in the amount of lamin A, rather than appearance of its truncated form, is responsible for growth retardation in affected cells. [source] A member of the YER057c/yjgf/Uk114 family links isoleucine biosynthesis and intact mitochondria maintenance in Saccharomyces cerevisiaeGENES TO CELLS, Issue 6 2001Jong-Myong Kim Background Two paralogs, YIL051c and YER057c, in the Saccharomyces cerevisiae genome are members of the YER057c/Yigf/Uk114 family, which is highly conserved among Eubacteria, Archaea and Eukarya. Although the molecular function of this protein family is not clear, previous studies suggest that it plays a role in the regulation of metabolic pathways and cell differentiation. Results Yil051cp is 70% identical in amino acid sequence to Yer057cp, and differs in that the former is longer by 16 amino acids containing, in part, the mitochondrial targeting signal at the N-terminus of the protein. An HA-tagged protein of Yil051cp is localized strictly in mitochondria, while that of Yer057cp is found in both cytoplasm and nucleus. Disruption of YIL051c (yil051c,) resulted in severe growth retardation in glucose medium due to isoleucine auxotroph, and no growth in glycerol medium due to the loss of mitochondria. An extract prepared from yil051c, cells showed no transaminase activity for isoleucine, while that for valine or leucine was intact. Haploid yil051c, cells newly isolated from the YIL051c/yil051c, hetero-diploids gradually lost mitochondrial DNA within 24 h in the absence of, but not in the presence of, an isoleucine. Mutants either requiring leucine (leu2,112) or isoleucine-valine (bat1,, bat2,) in a YIL051c background showed no changes in mitochondrial DNA maintenance in the absence of requirements. Conclusions Based on these results, we named Yil051c as Ibm1 (Isoleucine Biosynthesis and Mitochondria maintenance1) and concluded that: (i) Ibm1p determines the specificity of isoleucine biosynthesis, probably at the transamination step, (ii) Ibm1p is required for the maintenance of mitochondrial DNA when isoleucine is deficient, and (iii) Isoleucine compensates for the lack of Ibm1p. Taken together, Ibm1p may act as a sensor for isoleucine deficiency as well as a regulator determining the specificity for branched amino acid transaminase. [source] Identification and functional analysis of the gene for type I myosin in fission yeastGENES TO CELLS, Issue 3 2001Mika Toya Background Type I myosin is highly conserved among eukaryotes, and apparently plays important roles in a number of cellular processes. In the budding yeast, two myosin I species have been identified and their role in F-actin assembly has been inferred. Results We cloned the fission yeast myo1 gene, which apparently encoded a myosin I protein. Disruption of myo1 was not lethal, but it caused growth retardation at high and low temperatures, sensitivity to a high concentration of KCl, and aberrance in cell morphology associated with an abnormal distribution of F-actin patches. An abnormal deposition of cell wall materials was also seen. Homothallic myo1, cells could mate, but heterothallic myo1, cells were poor in conjugation. Myo1p was necessary for the encapsulation of spores. The tail domain of Myo1p was pivotal for its function. Calmodulin could bind to Myo1p through the IQ domain at the neck. Conclusions Myo1p appears to control the redistribution of F-actin patches during the cell cycle. Loss of Myo1p function is likely to slow down the actin assembly/disassembly process, which results in a failure of the actin cycle to catch up with other events in both the mitotic and meiotic cell cycles, including extension of the conjugation tubes. [source] Children of Helicobacter pylori -infected Dyspeptic Mothers are Predisposed to H. pylori Acquisition with Subsequent Iron Deficiency and Growth RetardationHELICOBACTER, Issue 3 2005Yao-Jong Yang Abstract Background., We tested whether Helicobacter pylori -infected dyspeptic mothers had a higher rate of H. pylori infection in their children, and whether such H. pylori -infected children were predisposed to iron deficiency or growth retardation. Materials and methods., A total of 163 children from 106 dyspeptic mothers (58 with and 48 without H. pylori infection) were enrolled to evaluate body weight, height, hemoglobin, serum ferritin, and H. pylori infection using the 13C-urea breath test. A questionnaire was used to evaluate demographic factors of each child. Results., The rate of H. pylori infection in children with H. pylori -infected dyspeptic mothers was higher than that of children with noninfected mothers (20.5% vs. 5.3%; p < .01, OR: 4.6, 95% CI: 1.5,14.2). The rate of H. pylori infection in children elevated as the number of their H. pylori -infected siblings increased (p < .01). For children below 10 years of age, H. pylori infection was closely related to low serum ferritin and body weight growth (p < .05). Conclusion., The children of H. pylori -infected dyspeptic mothers had an increased risk for such infection. The risk further increased once their siblings were infected. H. pylori infection in pre-adolescent children may determine iron deficiency and growth retardation. [source] ,-Glutamyltranspeptidase,deficient knockout mice as a model to study the relationship between glutathione status, mitochondrial function, and cellular functionHEPATOLOGY, Issue 4 2000Yvonne Will ,-Glutamyltranspeptidase (GGT)-deficient mice (GGT,/,) display chronic glutathione (GSH) deficiency, growth retardation, and die at a young age (<20 weeks). Using livers from these mice, we investigated the relationship between GSH content, especially mitochondrial, and mitochondrial and cellular function. We found that the GSH content of isolated liver mitochondria was diminished by ,50% in GGT,/, mice when compared with wild-type mice. Respiratory control ratios (RCRs) of GGT,/, mice liver mitochondria were ,60% those of wild-type mice primarily as a result of impaired state 3 respiration. Mitochondrial adenine nucleotide content was decreased by ,40% in mitochondria obtained from GGT,/, mice. We observed a strong correlation between mitochondrial GSH content and RCRs. Even moderate decreases (<50%) correlated with adverse effects with respect to respiration. Electron microscopy revealed that livers from GGT,/, knockout mice were deprived of fat and glycogen, and swollen mitochondria were observed in animals that were severely deprived of GSH. Thus, GGT,/, mice exhibit a loss of GSH homeostasis and impaired oxidative phosphorylation, which may be related to the rate of adenosine triphosphate (ATP) formation and subsequently leads to progressive liver injury, which characterizes the diseased state. We also found that supplementation of GGT,/, mice with N -acetylcysteine (NAC) partially restored liver GSH, but fully restored mitochondrial GSH and respiratory function. Electron microscopy revealed that the livers of NAC-supplemented GGT,/, mice contained fat and glycogen; however, slightly enlarged mitochondria were found in some livers. NAC supplementation did not have any beneficial effect on the parameters examined in wild-type mice. [source] OBSL1 mutations in 3-M syndrome are associated with a modulation of IGFBP2 and IGFBP5 expression levels,HUMAN MUTATION, Issue 1 2010Celine Huber Abstract 3-M syndrome is an autosomal recessive disorder characterized by severe pre- and postnatal growth retardation and minor skeletal changes. We have previously identified CUL7 as a disease-causing gene but we have also provided evidence of genetic heterogeneity in the 3-M syndrome. By homozygosity mapping in two inbred families, we found a second disease locus on chromosome 2q35,36.1 in a 5.2-Mb interval that encompasses 60 genes. To select candidate genes, we performed microarray analysis of cultured skin fibroblast RNA from one patient, looking for genes with altered expression; we found decreased expression of IGFBP2 and increased expression of IGFBP5. However, direct sequencing of these two genes failed to detect any anomaly. We then considered other candidate genes by their function/location and found nine distinct mutations in the OBSL1 gene in 13 families including eight nonsense and one missense mutations. To further understand the links between OBSL1, CUL7, and insulin-like growth factor binding proteins (IGFBPs), we performed real-time quantitative PCR (RT-PCR) analysis for OBSL1, CUL7, IGFBP2, and IGFBP5, using cultured fibroblast RNAs from two patients with distinct OBSL1 mutations (p.F697G; p.H814RfsX15). We found normal CUL7 mRNA levels but abnormal IGFBP2 and IGFBP5 mRNA levels in the two patients, suggesting that OBSL1 modulates the expression of IGFBP proteins. Hum Mutat 30:1,7, 2009. © 2009 Wiley-Liss, Inc. [source] Rapid detection of methylation change at H19 in human imprinting disorders using methylation-sensitive high-resolution melting,HUMAN MUTATION, Issue 10 2008Tomasz K. Wojdacz Abstract Beckwith Wiedemann syndrome (BWS) and Russell Silver syndrome (RS) are growth disorders with opposing epimutations affecting the H19/IGF2 imprinting center at 11p15.5. Overgrowth and tumor risk in BWS is caused by aberrant expression of the paternally expressed, imprinted IGF2 gene, occurring as a consequence of mosaic hypermethylation within the imprinting center, or to mosaic paternal uniparental disomy (UPD). RS is characterized by severe intrauterine growth retardation (IUGR). A subset of RS cases were recently shown to have mosaic hypomethylation within the H19/IGF2 imprinting center, predicted to silence paternally expressed IGF2 in early development. Molecular diagnosis for BWS and RS involves methylation analysis of the H19 locus, enabling discrimination of allelic methylation patterns. In this study, methylation-sensitive high-resolution melting analysis (MS-HRM) was used to analyze methylation within the intergenic region of the H19 locus. A total of 36 samples comprising normal control (11), BWS (19), and RS (six) DNA were analyzed in a blinded study and scored as hypermethylated, normal, or hypomethylated. Results were compared with those derived by methylation-sensitive Southern blotting using the restriction enzymes Rsa I and Hpa II. A total of 100% concordance was obtained for the Southern blotting and MS-HRM scores. A total of three samples with paternal duplication affecting the H19/IGF2 region were scored as equivocal by both methods; however, 33 out of 36 (92%) the samples were unambiguously scored as being hypermethylated, hypomethylated, or normally methylated using MS-HRM. We conclude that MS-HRM is a rapid, cost-effective, and sensitive method for screening mosaic methylation changes at the H19 locus in BWS and RS. Hum Mutat 0,1,6, 2008. © 2008 Wiley-Liss, Inc. [source] Clinical features of maternal uniparental disomy 14 in patients with an epimutation and a deletion of the imprinted DLK1/GTL2 gene cluster,,HUMAN MUTATION, Issue 9 2008Karin Buiting Abstract Maternal uniparental disomy 14 [upd(14)mat] is associated with a recognizable phenotype that includes pre- and postnatal growth retardation, neonatal hypotonia, feeding problems and precocious puberty. Chromosome 14 contains an imprinted gene cluster, which is regulated by a differentially methylated region (IG-DMR) between DLK1 and GTL2. Here we report on four patients with clinical features of upd(14)mat who show a maternal-only methylation pattern, but biparental inheritance for chromosome 14. In three of the patients loss of paternal methylation appears to be a primary epimutation, whereas the other patient has a paternally derived deletion of ,1,Mb that includes the imprinted DLK1-GTL2 gene cluster. These findings demonstrate that the upd(14)mat phenotype is caused by altered expression of genes within this cluster. Hum Mutat 0, 1,6, 2008. © 2008 Wiley-Liss, Inc. [source] Expression of IL-27 in murine carcinoma cells produces antitumor effects and induces protective immunity in inoculated host animalsINTERNATIONAL JOURNAL OF CANCER, Issue 3 2005Masako Chiyo Abstract A novel cytokine interleukin-27 (IL-27), composed of p28 and Epstein-Barr virus-induced gene 3 (EBI3), is produced from activated dendritic cells and is involved in an early phase of T-helper type I differentiation. We examined whether Colon 26 murine colon carcinoma cells that were retrovirally transduced with the p28 -linked EBI3 gene (Colon 26/IL-27) could produce antitumor effects in inoculated mice. Although proliferation in vitro of Colon 26/IL-27 cells was not different from that of parent cells, syngeneic BALB/c mice rejected Colon 26/IL-27 tumors inoculated and subsequently acquired tumor-specific protective immunity. In contrast, mice inoculated with Colon 26 cells transduced with either the p28 or EBI3 gene developed tumors and survival of the mice remained the same as that of the mice inoculated with parent cells. Syngeneic nude mice developed Colon 26/IL-27 tumors, but the growth was retarded compared to that of parent tumors. Depletion of natural killer cells from nude mice with anti-asialo GM1 antibody diminished the growth retardation of Colon 26/IL-27 tumors. Survival of severe combined immunodeficient mice that received subcutaneous inoculation of Colon 26/IL-27 cells was not different from that of the immunodeficient mice inoculated with parent cells. Interferon-, was produced from CD4+ and CD8+ T, and natural killer cells of the mice that rejected Colon 26/IL-27 tumors and cytotoxic activity against Colon 26 cells were also detected from the mice. These data collectively suggest that expressed IL-27 in tumors produces T cell-dependent and-independent antitumor effects and is a possible therapeutic strategy for cancer. ©2005 Wiley-Liss, Inc. [source] Systemic and local effects of long-term exposure to alkaline drinking water in ratsINTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, Issue 4 2001Marina E.T. Merne Alkaline conditions in the oral cavity may be caused by a variety of stimuli, including tobacco products, antacids, alkaline drinking water or bicarbonate toothpaste. The effects of alkaline pH on oral mucosa have not been systematically studied. To assess the systemic (organ) and local (oral mucosal) effects of alkalinity, drinking water supplemented with Ca(OH)2 or NaOH, with pH 11.2 or 12 was administered to rats (n = 36) for 52 weeks. Tissues were subjected to histopathological examination; oral mucosal biopsy samples were also subjected to immunohistochemical (IHC) analyses for pankeratin, CK19, CK5, CK4, PCNA, ICAM-1, CD44, CD68, S-100, HSP 60, HSP70, and HSP90. At completion of the study, animals in the study groups had lower body weights (up to 29% less) than controls despite equal food and water intake, suggesting a systemic response to the alkaline treatment. The lowest body weight was found in rats exposed to water with the highest pH value and starting the experiment when young (6 weeks). No histological changes attributable to alkaline exposure occurred in the oral mucosa or other tissues studied. Alkaline exposure did not affect cell proliferation in the oral epithelium, as shown by the equal expression of PCNA in groups. The up-regulation of HSP70 protein expression in the oral mucosa of rats exposed to alkaline water, especially Ca(OH)2 treated rats, may indicate a protective response. Intercellular adhesion molecule-1 (ICAM-1) positivity was lost in 6/12 rats treated with Ca(OH)2 with pH 11.2, and loss of CD44 expression was seen in 3/6 rats in both study groups exposed to alkaline water with pH 12. The results suggest that the oral mucosa in rats is resistant to the effects of highly alkaline drinking water. However, high alkalinity may have some unknown systemic effects leading to growth retardation, the cause of which remains to be determined. [source] Differential developmental toxicities of di- n -hexyl phthalate and dicyclohexyl phthalate administered orally to ratsJOURNAL OF APPLIED TOXICOLOGY, Issue 6 2009Anne-Marie Saillenfait Abstract The objective of this study was to evaluate the developmental toxic potential of di- n -hexyl phthalate (DnHP) and dicyclohexyl phthalate (DCHP) in rats. Pregnant Sprague,Dawley rats were exposed to DnHP or DCHP at doses of 0 (olive oil), 250, 500 and 750 mg kg,1 per day, by gavage, on gestational days (GD) 6,20. Maternal food consumption and body weight gain were significantly reduced at 750 mg kg,1 per day of DnHP and at the two high doses of DCHP. Slight changes in liver weight associated with peroxisomal enzyme induction were seen in dams treated with DnHP or DCHP. DnHP caused dose-related developmental toxic effects, including marked embryo mortality at 750 mg kg,1 per day, and presence of malformations (mainly cleft palate, eye defects and axial skeleton abnormalities) and significant decreases in fetal weight at 500 and 750 mg kg,1 per day. Significant delay of ossification and increase in the incidence of skeletal variants (e.g. supernumerary lumbar ribs) also appeared at 250 mg kg,1 per day. DCHP produced fetal growth retardation at 750 mg kg,1 per day, as evidenced by significant reduction of fetal weight. DnHP and DCHP induced a significant and dose-related decrease in the anogenital distance of male fetuses at all doses, and there was a significant increase in the incidence of male fetuses with undescended testis at 500 and 750 mg kg,1 per day of DnHP. In conclusion, DnHP showed clear embryolethality and teratogenicity, but not DCHP. There was evidence that both phthalates could alter the development of the male reproductive system after in utero exposure, DnHP being much more potent than DCHP. Copyright © 2009 John Wiley & Sons, Ltd. [source] Glucocorticoid Excess During Adolescence Leads to a Major Persistent Deficit in Bone Mass and an Increase in Central Body FatJOURNAL OF BONE AND MINERAL RESEARCH, Issue 10 2001Veronica Abad Abstract Endogenous Cushing's syndrome (CS) in children causes growth retardation, decreased bone mass, and increased total body fat. No prospective controlled studies have been performed in children to determine the long-term sequelae of CS on peak bone mass and body composition. A 15-year-old girl with Cushing disease (CD), and her healthy identical co-twin, were followed for 6 years after the CD was cured. At the 6-year follow-up both twins had areal bone mineral density (BMD) and body composition determined by dual-energy X-ray absorptiometry (DXA) and three-dimensional quantitative computed tomography (3DQCT). Z scores for height, weight, and body mass index (BMI) were ,2.3, ,0.8 and 0.2, and 1.2, 0.2, and ,0.6, in the twin with CD and her co-twin, respectively. In the twin with CD, areal BMD and bone mineral apparent density (BMAD) at different sites varied from 0.7 to 3 SD below her co-twin. Volumetric lumbar spine bone density Z score was ,0.75 and 1.0, and total body, abdominal visceral, and subcutaneous fat (%) was 42, 10, and 41 versus 26, 4, and 17 in the twin with CD and her co-twin, respectively. The relationship between total body fat and L2-L4 BMAD was inverse in the twin with CD (p < 0.05), which by contrast in her co-twin was opposite and direct (p < 0.001). In the twin with CD, despite cure, there was a persistent deficit in bone mass and increase in total and visceral body fat. These observations suggest that hypercortisolism (exogenous or endogenous) during adolescence may have persistent adverse effects on bone and fat mass. [source] | ||||||||||||||||||||||||||||||||||||||||