Showing papers by "Montreal Children's Hospital published in 2001"
TL;DR: Transient nuclear localization of Dnmt1o in 8-cell embryos suggests that this variant of DNmt1 provides maintenance methyltransferase activity specifically at imprinted loci during the fourth embryonic S phase.
699 citations
TL;DR: The Ala222Val MTHFR, however, has an enhanced propensity to dissociate into monomers and to lose its FAD cofactor on dilution; the resulting loss of activity is slowed in the presence of methyltetrahydrofolate or adenosylmethionine.
Abstract: Methylenetetrahydrofolate reductase (MTHFR) catalyzes the conversion of methylenetetrahydrofolate to methyltetrahydrofolate, the major methyl donor for the conversion of homocysteine to methionine. Two common polymorphisms of the human enzyme have been identified: 677C>T, which leads to the substitution of Ala-222 by valine, and 1298A>C, which leads to the replacement of Glu-429 by alanine; the former polymorphism is the most frequent genetic cause of mild hyperhomocysteinemia, a risk factor for cardiovascular disease. By using a baculovirus expression system, recombinant human MTHFR has been expressed at high levels and purified to homogeneity in quantities suitable for biochemical characterization. The Glu429Ala protein has biochemical properties that are indistinguishable from the wild-type enzyme. The Ala222Val MTHFR, however, has an enhanced propensity to dissociate into monomers and to lose its FAD cofactor on dilution; the resulting loss of activity is slowed in the presence of methyltetrahydrofolate or adenosylmethionine. This biochemical phenotype is in good agreement with predictions made on the basis of studies comparing wild-type Escherichia coli MTHFR with a mutant, Ala177Val, homologous to the Ala222Val mutant human enzyme [Guenther, B. D., et al. (1999) Nat. Struct. Biol. 6, 359–365].
391 citations
TL;DR: Nasal fluticasone decreased the frequency of mixed and obstructive apneas and hypopneas, suggesting that topical corticosteroids may be helpful in ameliorating pediatric obstructive sleep apnea.
352 citations
TL;DR: CCAM can lead to fetal or neonatal demise from hydrops, lung hypoplasia, prematurity or severe associated malformations, but has a good prognosis in the majority of cases.
Abstract: Congenital cystic adenomatoid malformation of the lung (CCAM) is diagnosed by prenatal ultrasonography with an increasing frequency but controversy persists as to its prognosis and prenatal management
338 citations
TL;DR: This review summarizes the biochemical basis and clinical evidence for interactions between MTHFR polymorphisms and several disease entities, as well as potential interactions with drug therapies.
Abstract: 5,10-Methylenetetrahydrofolate reductase (MTHFR) plays a key role in folate metabolism by channeling one-carbon units between nucleotide synthesis and methylation reactions. Severe enzyme deficiency leads to hyperhomocysteinemia and homocystinuria, with altered folate distribution and a phenotype that is characterized by damage to the nervous and vascular systems. Two frequent polymorphisms in the human MTHFR gene confer moderate functional impairment of MTHFR activity for homozygous mutant individuals. The C to T change at nucleotide position 677, whose functional consequences are dependent on folate status, has been extensively studied for its clinical consequences. A second polymorphism, an A to C change at nucleotide position 1298, is not as well characterized. Still equivocal are associations between MTHFR polymorphisms and vascular arteriosclerotic or thrombotic disease. Neural tube defects and pregnancy complications appear to be linked to impaired MTHFR function. Colonic cancer and acute leukemia, however, appear to be less frequent in individuals homozygous for the 677T polymorphism. MTHFR polymorphisms influence the homocysteine-lowering effect of folates and could modify the pharmacodynamics of antifolates and many other drugs whose metabolism, biochemical effects, or target structures require methylation reactions. However, only preliminary evidence exists for gene-drug interactions. This review summarizes the biochemical basis and clinical evidence for interactions between MTHFR polymorphisms and several disease entities, as well as potential interactions with drug therapies. Future investigations of MTHFR in disease should consider the influence of other variants of functionally-related genes as well as the medication regimen of the patients. Animal models for genetic deficiencies in folate metabolism will likely play a greater role in our understanding of folate-dependent disorders.
192 citations
TL;DR: The literature that has described the developmental outcome of asphyxiated term newborns is reviewed and appropriate markers that should be used in future research on this population are delineated.
Abstract: Asphyxia remains one of the main causes of later disability in term infants. Despite many publications identifying possible predictors of outcome in this population of interest, little is known of the long-term developmental outcome of asphyxiated term neonates. Observational studies have largely focused on short-term outcomes, with an emphasis on significant neurologic sequelae and intellectual impairments. This article reviews the literature that has described the developmental outcome of asphyxiated term newborns. As part of this review, we have also highlighted the evolution of the definition of asphyxia and delineated appropriate markers that should be used in future research on this population.
185 citations
TL;DR: The inclusion of an impairment criterion had a significant impact in reducing the prevalence rates of overall psychiatric disorders, mainly through impairment's effects on internalizing disorders, specifically anxiety-based disorders (i.e., simple and social phobia).
Abstract: The present study examined psychiatric functioning in a community sample of adolescents aged 14 to 17 years (average age of 15 years). We administered the Diagnostic Interview Schedule for Children-2.25 (DISC-2.25) to 1,201 adolescents and their mothers to obtain prevalence estimates of DSM-III-R disorders and the amount of perceived impairment associated with these disorders. While adolescent females reported a significantly higher prevalence of psychiatric disorders than males (15.5% vs. 8.5%), mothers indicated no sex difference. Compared with adolescent males, females had significantly higher rates of internalizing, anxiety. and depressive disorders. In contrast, the prevalence of externalizing disorders was significantly higher among adolescent males. The inclusion of an impairment criterion had a significant impact in reducing the prevalence rates of overall psychiatric disorders. This reduction occurred mainly through impairment's effects on internalizing disorders, specifically anxiety-based disorders (i.e., simple and social phobia). Given the limited research on the effect of impairment on the prevalence of adolescent psychiatric disorders, future work in this area seems warranted.
167 citations
TL;DR: The high prevalence of functional limitations and dependence in activities of daily living is currently underappreciated in the clinical setting, and deserves additional attention by pediatricians and developmental specialists.
Abstract: UNLABELLED With the recent dramatic decline in mortality rates of infants undergoing open-heart surgery (OHS), there is growing concern regarding neurodevelopmental sequelae. Outcome studies have primarily focused on delineating developmental impairments; however, the impact on function and family burden has not been investigated. The objective of this study was to determine the prevalence of functional limitations and burden of care of young children with congenital heart defects (CHD) after OHS. STUDY DESIGN One hundred thirty-one eligible infants with CHD undergoing their first OHS were recruited prospectively. Patients were assessed pre- and postoperatively, and again 12 to 18 months after surgery. Functional assessments included the WeeFIM (Functional Independence Measure) and the Vineland Adaptive Behavior Scale. RESULTS For the WeeFIM, mean quotients were 84.3 +/- 23.8 (self-care), 77.2 +/- 30.0 (mobility), and 92.4 +/- 27.8 (cognition), with an overall quotient of 83.8 +/- 23.4. Only 21% of the cohort was functioning within their expected age range. Moderate disability was noted in 37%, while only 6% demonstrated a severe disability. For the Vineland scale, mean score for daily living skills was 84.4 +/- 17.6, and 80.3 +/- 15.9 for socialization. Functional difficulties in daily living skills were documented in 40%, whereas >1/2 had poor socialization skills. Factors enhancing risk for functional disabilities included perioperative neurodevelopmental status, microcephaly, length of deep hypothermic circulatory arrest, length of stay in the intensive care unit, age at surgery, and maternal education. CONCLUSIONS The high prevalence of functional limitations and dependence in activities of daily living is currently underappreciated in the clinical setting, and deserves additional attention by pediatricians and developmental specialists.
165 citations
TL;DR: The proportion of sequestrations that were atypical or associated with other entities, such as congenital cystic adenomatoid malformations, communicating bronchopulmonary foregut malformation, bronchogenic cyst, and scimitar syndrome, was identified.
145 citations
TL;DR: Focal/conformal radiotherapy has an adjuvant role but better treatments are needed for the diffuse pontine brainstem lesions, and the relative impact of radical surgery and/or radiotherapy is analysed.
Abstract: Case records of 37 patients with a diagnosis of brainstem glioma treated at the Montreal Children's Hospital from June 1989 to June 1999 were reviewed. 15 patients had diffuse pontine gliomas and 22 patients had focal forms of brainstem gliomas. The two groups were compared with respect to age, clinical evolution, radiological appearance, type of surgery practised, histological diagnosis, adjuvant treatments and survival. A non-pontine brainstem location, a cystic or exophytic component, bright enhancement with gadolinium injection, a histological diagnosis of pilocytic astrocytoma or ganglioglioma were favourable prognostic factors. Progression-free survival and overall survival were significantly worse in the group of patients with diffuse pontine gliomas. The relative impact of radical surgery and/or radiotherapy is analysed. Surgery coupled to adjuncts such as navigation, ultrasound and monitoring plays an important role for focal brainstem lesions. Focal/conformal radiotherapy has an adjuvant role but better treatments are needed for the diffuse pontine brainstem lesions.
99 citations
TL;DR: An 11-year retrospective cohort study of neonates, who were identified through computer database records and were admitted to the Neonatal Intensive Care Unit from January 1989 to December 1999 at the Montreal Children's Hospital, is presented.
TL;DR: The molecular basis of T2 enzyme deficiency in 26 patients at the levels of skin fibroblast enzyme activity, protein integrity, and DNA nucleotide sequence was determined and genotype does not predict clinical severity and mutant sibs can have different clinical phenotypes.
TL;DR: It is suggested that PHEX activity and mineralization may be controlled in vivo by PP(i)/P(i) and Ca(2+) and, in the latter case, the regulation requires the participation of osteocalcin.
Abstract: Mutations in the PHEX gene (phosphate-regulating gene with homologies to endopeptidases on the X chromosome) are responsible for X-linked hypophosphataemia, and studies in the Hyp mouse model of the human disease implicate the gene product in the regulation of renal phosphate (P(i)) reabsorption and bone mineralization. Although the mechanism for PHEX action is unknown, structural homologies with members of the M13 family of endopeptidases suggest a function for PHEX protein in the activation or degradation of peptide factors involved in the control of renal P(i) transport and matrix mineralization. To determine whether PHEX has endopeptidase activity, we generated a recombinant soluble, secreted form of human PHEX (secPHEX) and tested the activity of the purified protein with several peptide substrates, including a variety of bone-related peptides. We found that parathyroid-hormone-related peptide(107-139) is a substrate for secPHEX and that the enzyme cleaves at three positions within the peptide, all located at the N-terminus of aspartate residues. Furthermore, we show that osteocalcin, PP(i) and P(i), all of which are abundant in bone, are inhibitors of secPHEX activity. Inhibition of secPHEX activity by osteocalcin was abolished in the presence of Ca(2+). We suggest that PHEX activity and mineralization may be controlled in vivo by PP(i)/P(i) and Ca(2+) and, in the latter case, the regulation requires the participation of osteocalcin.
TL;DR: It is speculated that a metabolite downstream from the hormone-sensitive lipase reaction may be essential for membrane stabilization and integrity in the seminiferous epithelium and, in particular, may play an important role in the maintenance of intercellular cytoplasmic bridges between postmeiotic germ cells.
Abstract: The 84-kDa hormone-sensitive lipase (gene designation Lipe; EC 3.1.1.3) is a cholesterol esterase and triglyceride hydrolase that functions in the release of fatty acids from adipocytes. The role of hormone-sensitive lipase in other tissues such as the testis, where a specific 120-kDa testis-specific isoform is expressed, is unknown. To study this, we examined the fertility and testicular histology of gene-targeted hormone-sensitive lipase-deficient mice. Homozygous hormone-sensitive lipase-deficient male mice are infertile and have decreased testis weights; female homozygotes are fertile. Testicular abnormalities, detected at the light and electron microscopic levels, included the presence of multinucleated round and elongating spermatids, vacuolization of the seminiferous epithelium, asynchronization of the spermatogenic cycle, sloughing of postmeiotic germ cells from the seminiferous epithelium into the lumen, and a marked reduction in the numbers of late spermatids. Extensive nuclear head deformation ...
TL;DR: Liver STAT5 is repeatedly activated by successive, spontaneous GH secretory episodes in intact adult male rats at approximately 3- to 3.5-h intervals and the lower level of liver STAT5 activation seen in adult female rats, compared with males, is a consequence of the sex-dependent differences inGH secretory patterns that characterize these animals.
Abstract: STAT5 transduces transcriptional responses to GH in liver and other tissues and is proposed to mediate the sexually dimorphic effects of plasma GH secretory profiles on rodent liver gene expression. Previous studies have suggested that STAT5 undergoes repeated activation in direct response to successive GH pulses in adult male rats, with STAT5 activation being desensitized in females by their more persistent pattern of GH exposure. These findings, however, were based on in vitro studies or single blood samples analyzed for GH in vivo. In view of the highly pulsatile nature of rat GH secretion, we presently examined these hypotheses by concurrent monitoring of spontaneous GH secretory profiles and hepatic STAT5 activity in conscious, free-moving adult male and female rats. Rats were killed at times associated with spontaneous peaks or troughs of the GH rhythm; livers were removed and analyzed for STAT5 DNA-binding activity. In males, liver STAT5 activity was highest during the initial phase (15–60 min) of ...
TL;DR: A DNA fingerprinting method is developed for detecting two putative "silencing" alleles found in two thymus samples, which supports a thymic enhancer effect of the INS variable number of tandem repeats as the mechanism of IDDM2 and refines the contribution of ID DM2 genotyping to diabetes risk assessment.
Abstract: Type 1 diabetes results from autoimmune destruction of the insulin-producing pancreatic β cells. The insulin gene (INS) is also expressed in human thymus, an ectopic expression site likely involved in immune tolerance. The IDDM2 diabetes susceptibility locus maps to a minisatellite composed of a variable number of tandem repeats situated 0.5 kb upstream of INS. Chromosomes carrying the protective long INS variable number of tandem repeats alleles (class III) produce higher levels of thymic INS mRNA than those with the predisposing, short class I alleles. However, complete silencing of thymic INS transcripts from the class III chromosome was found in a small proportion of heterozygous human thymus samples. We hypothesized that the specific class III alleles found on these chromosomes silence rather than enhance thymic insulin expression. To test the prediction that these alleles are predisposing, we developed a DNA fingerprinting method for detecting two putative “silencing” alleles found in two thymus sam...
TL;DR: The results suggest that providing a caregiving context when painful procedures are performed may be a simple and practical method of reducing pain experience in infants, and that no one measure captures these effects.
Abstract: To understand how the 'caregiving context' could affect responses to procedural pain, the authors sought to determine whether (1) the combined effects of sweet taste and holding (caregiving contact) were greater than the effects of either alone, (2) any combined effects were additive or interactive, and (3) the interventions had similar effects on behavioral (crying and facial activity) and physiological (heart rate, vagal tone) responses to the heel-stick procedure in newborn infants in a randomized two-factorial intervention trial. Eighty-five normally developing newborn infants were studied with a mean gestational age of 39.4 weeks on the 2nd or 3rd day of life. Infants were randomized in blocks of eight to receive (1) no holding and water taste (control participants), (2) no holding and sucrose taste (sucrose group), (3) holding and water taste (holding group), or (4) holding and sucrose taste (holding and sucrose group). Crying was reduced significantly by taste and holding, and the interventions combined additively. Facial activity was only significantly reduced by holding. For physiological measures, the interventions interacted with each other and preintervention levels to reduce heart rate and lower vagal tone more during the procedure in infants in whom heart rate and vagal tone were higher before intervention. Consequently, sweet taste and holding interventions combined in complex ways when acting on different behavioral and physiological response systems to modify stressful pain experiences. The results suggest that providing a caregiving context when painful procedures are performed may be a simple and practical method of reducing pain experience in infants, and that no one measure captures these effects.
TL;DR: In conclusion, the incidence of PTLD varies widely across Canadian centres, children are disproportionately affected and the mortality rate is high, and the need for information sharing was identified as one way of optimizing management.
Abstract: The aim of this work was to obtain information on the magnitude of the problem, disease characteristics, and clinical practices relating to post-transplant lymphoproliferative disease (PTLD) in Canadian institutions. Adult and pediatric Canadian solid organ transplant groups were sent a questionnaire between July and October 1998. Analyzable data were obtained from 33 transplant groups. For the period 1988-97, 90 cases of PTLD were seen among 4283 solid organ transplant recipients. The incidence of PTLD varied from 0 to 14.6%, with the highest rates in children. Lymph nodes were the sites most frequently affected. Among the classifiable lesions, the majority were monoclonal. The lesions were of B-cell origin in 42.2% and of T-cell in 15.6%. The lesions were classified as monomorphic in 31.1%, polymorphic 18.9%, and hyperplastic in 1.1%. Tumors were reported as low grade in 26.7% and high grade in 10%. The majority of patients (71.1%) received reduced immunosuppression. Anti-viral agents were used in 52.2%. Chemotherapy was used in 27.8%, while immune globulin was used in 22.2%. Surgical resection was used in 20.0%, radiotherapy in 14.4%, and interferon-alpha therapy in 12.2%. The results showed that 48.9% of the patients had died, while 25.6% and 8.9% were regarded as having complete remission and partial remission, respectively. In conclusion, the incidence of PTLD varies widely across Canadian centres. Children are disproportionately affected and the mortality rate is high. Management practices vary significantly, and the need for information sharing was identified as one way of optimizing management.
TL;DR: Linkage analysis indicated that the two NPT2 intragenic SNP as well as five microsatellite markers in the N PT2 gene region were not linked to HHRH in the Bedouin kindred, evidence to exclude NPT1 as a candidate gene for HHRh in the families that were studied.
Abstract: Hereditary hypophosphatemic rickets with hypercalciuria (HHRH), a renal phosphate (Pi) wasting disease first described in an extended Bedouin kindred, is characterized by hypophosphatemia, elevated serum 1,25-dihydroxyvitamin D levels, hypercalciuria, rickets, and osteomalacia. Correction of all abnormalities, except for renal Pi wasting, can be achieved by oral Pi supplementation. These findings and the demonstration that mice that are homozygous for the disrupted Na/Pi cotransporter gene Npt2 exhibit many of the biochemical features of HHRH suggested that mutations in the human orthologue NPT2 might be responsible for HHRH. The NPT2 gene in affected individuals from the Bedouin kindred and four small families was screened for mutations to test this hypothesis. No putative disease-causing mutation was found. Two single nucleotide polymorphisms (SNP), a silent substitution in exon 7 and a nucleotide substitution in intron 4, were identified, and neither consistently segregated with HHRH in the Bedouin kindred. Linkage analysis indicated that the two NPT2 intragenic SNP as well as five microsatellite markers in the NPT2 gene region were not linked to HHRH in the Bedouin kindred. Therefore, this is evidence to exclude NPT2 as a candidate gene for HHRH in the families that were studied.
TL;DR: It was demonstrated that based on a global measure of smiling, the emotional atmosphere was less positive in tetrads than in dyads, and this hypothesis was not supported for females.
Abstract: The present research was designed to test the hypothesis that children would compete more in tetrads than in dyads. Twenty-two pairs of male and 14 pairs of female target children (N = 72) played a competitive game in both tetrads and dyads. Consistent with the hypothesis, male target children competed more in tetrads than in dyads. This hypothesis was not supported for females, however. Analyses of the dynamics of tetrads and dyads further demonstrated that based on a global measure of smiling, the emotional atmosphere was less positive in tetrads than in dyads. The causes and consequences of interaction in different sized social groups are discussed.
TL;DR: Two Mayan communities of retornados (returnees), whose paths into exile and home again differ slightly, are compared and shows how small changes in the migration experience may result in considerable differences in the choice of strategies.
Abstract: Around 1982, thousands of Guatemalan Mayas fled their villagesand lands to escape the Rios Montt scorched-earth policyimplemented in rural areas. After more than a decade of exile,many of those refugees have returned to their homeland. Thispaper looks at the ways in which young Mayan refugees who havereturned home after extended exile in Mexico appropriate anddistance themselves from the collective project of going home. Two Mayan communities of retornados (returnees), whose paths into exile and home again differ slightly, are compared. Outsidesupport from international organizations and cohesion in therefugee camps enabled the young people of La Victoria to seedisclosure of the traumatic past from a position of strength andconfrontation as the key to social change. In La Esperanza, thepast is rebuilt by the youth around avoidance of recent history,and tradition appears as a bridge between past and future. Theway the youth of the two communities construct their homecomingdemonstrates how small changes in the migration experience mayresult in considerable differences in the choice of strategies,and raises important questions about assistance programs thatmight be developed for these populations.
TL;DR: The shaping achieved by TO in terms of lung growth, structural maturity, and pulmonary artery medial area thinning may prove beneficial in lessening the severity of the associated pulmonary hypertension in CDH.
TL;DR: This poster focuses on the use of a single prick skin test (PST) for peanut allergy diagnosis and its application in patients with a history of food allergy.
Abstract: Background Accurate diagnosis of peanut allergy is essential given that it is a lifelong and potentially fatal food allergy. Diagnosis relies on patient history, prick skin test (PST), and in many situations, food challenge. More information is required on the safety of food challenge and the informational value of a PST. Objectives Primary: to assess the safety of peanut challenges. Secondary: to estimate the sensitivity, specificity, and the positive and negative predictive values of PST to peanut performed in those who underwent a peanut challenge. Methods A retrospective study of peanut challenges performed at a tertiary care paediatric hospital allergy clinic between January 1994 and November 1998. Results Of the 140 peanut challenges performed on 140 patients, 18 were positive The most frequent adverse clinical effects of positive peanut challenges were: urticaria, oropharyngeal irritation, rhinitis, vomiting and abdominal pain. Among the 18 patients who had a positive result, 10 required medical treatment (antihistamines, ± epinephrine, ± salbutamol) to control the allergic reaction. The sensitivity, specificity, and the positive and negative predictive values of PST to peanut in this group of children undergoing a peanut challenge were 100%, 62.3%, 28.1% and 100%, respectively. Conclusions Given the poor positive predictive value and specificity of PST, a peanut challenge is usually required to diagnose peanut allergy with certainty when the PST is positive. In cases of a clear history of anaphylaxis to peanut and a positive PST, challenges are unwarranted. When the history is strongly suggestive and the PST is borderline positive, i.e. 3 or 4 mm, peanut challenge is generally necessary to confirm the diagrosis. Given the excellent negative predictive value and sensitivity of PST, a blinded peanut challenge is usually unnecessary in the context of a negative PST except for patients with a history strongly suggestive of immediate hypersensitivity. These patients should be individually assessed for the need to undergo a blinded challenge. The peanut challenge is a useful and safe diagnostic tool when performed by qualified personnel under appropriate conditions.
TL;DR: It is demonstrated that essential pediatric resuscitation equipment is unavailable in a disturbingly high number of EDs across Canada and has identified several determinants of this unavailability.
TL;DR: Four clinically mild patients and their mutations in PMM2 carry a severe mutation that decreased the PMM activity to less than 10% as well as a relatively mild mutation that changed the reading frame.
TL;DR: Clinical findings are still the mainstay for suspecting the diagnosis of musculoskeletal infections, especially osteomyelitis, and current radiopharmaceuticals used for diagnosing infection also label inflammation.
TL;DR: The modified biofeedback program including appropriate explanations and psychological approaches appeared effective for treating 92% of children with detrusor-sphincter dyssynergia, less invasive and requires less time than traditional methods, and patients are more compliant with treatment.
TL;DR: The mechanism for the increased circulating levels of 1,25-(OH)2D in Npt2−/− mice was determined and whether renal 1α-hydroxylase was appropriately regulated by dietary Pi in the absence of NPT2 gene expression was established.
Abstract: Several reports have suggested that the regulation of renal 1,25-dihydroxyvitamin D [1,25-(OH)(2)D] synthesis by extracellular phosphate (Pi) is dependent on normal transepithelial Pi transport by the renal tubule. Mice homozygous for the disrupted Na/Pi cotransporter gene Npt2 (Npt2(-/-)) exhibit renal Pi wasting, an approximately 85% decrease in renal brush border membrane Na/Pi cotransport, hypophosphatemia, and an increase in serum 1,25-(OH)(2)D concentration. We undertook 1) to determine the mechanism for the increased circulating levels of 1,25-(OH)(2)D in Npt2(-/-) mice and 2) to establish whether renal 1alpha-hydroxylase was appropriately regulated by dietary Pi in the absence of Npt2 gene expression. On a control diet, the 2.5-fold increase in the serum 1,25-(OH)(2)D concentration in Npt2(-/-) mice, relative to that in Npt2(+/+) littermates, is associated with a corresponding increase in renal mitochondrial 25-hydroxyvitamin D-1 alpha-hydroxylase (1 alpha-hydroxylase) activity and messenger RNA (mRNA) abundance. A low Pi diet elicits an increase in serum 1,25-(OH)(2)D concentration, renal 1alpha-hydroxylase activity, and mRNA abundance in Npt2(+/+) and Npt2(-/-) mice to similar levels in both mouse strains. A high Pi diet has no effect on serum 1,25-(OH)(2)D concentration, renal 1 alpha-hydroxylase activity, or mRNA abundance in Npt2(+/+) mice, but normalizes these parameters in Npt2(-/-) mice. In addition, renal 24-hydroxylase mRNA abundance is significantly reduced in Npt2(-/-) mice compared with that in Npt2(+/+) mice under all dietary conditions. In summary, we demonstrate that 1) increased renal synthesis of 1,25-(OH)(2)D is responsible for the increased serum 1,25-(OH)(2)D concentration in Npt2(-/-) mice; and 2) renal 1alpha-hydroxylase gene expression is appropriately regulated by dietary manipulation of serum Pi in both Npt2(+/+) and Npt2(-/-) mice. Thus, intact renal Na/Pi cotransport is not required for the regulation of renal 1alpha-hydroxylase by Pi.
TL;DR: The finding that lung morphology was improved in CDH with TO with or without TR animals implies that prophylactic surfactant at birth might be beneficial for CDH, and indicates that these experimental lambs may experience respiratory insufficiency soon after birth.
TL;DR: Systemic steroid pretreatment significantly reduced total body edema and cerebral vascular leak and was associated with better immunohistochemical indices of neuroprotection after DHCA.