Literature search from ms 29/4/2010

Bachetti, T., P. Bocca, et al. (2007). "Geldanamycin promotes nuclear localisation and clearance of PHOX2B misfolded proteins containing polyalanine expansions." International Journal of Biochemistry & Cell Biology 39(2): 327-39.

Polyalanine expansions in the PHOX2B gene have been detected in the vast majority of patients affected with congenital central hypoventilation syndrome, a neurocristopathy characterized by absence of adequate control of breathing, especially during sleep, with decreased sensitivity to hypoxia and hypercapnia. The correlation between length of the alanine expanded tracts and severity of congenital central hypoventilation syndrome respiratory phenotype has been confirmed by length-dependent cytoplasmic PHOX2B retention with formation of aggregates. To deepen into the molecular mechanisms mediating the effects of PHOX2B polyalanine expansions, we have set up experiments aimed at assessing the fate of cells characterized by PHOX2B polyalanine aggregates. In particular, we have observed that activation of the heat shock response by the drug geldanamycin is efficient both in preventing formation and in inducing clearance of PHOX2B pre-formed polyalanine aggregates in COS-7 cells expressing PHOX2B-GFP fused proteins, and ultimately also in rescuing the PHOX2B ability to transactivate the Dopamine-beta-Hydroxilase promoter. In addition, we have demonstrated elimination of PHOX2B mutant proteins by the proteasome and autophagy, two cellular mechanisms already been involved in the clearance of proteins containing expanded polyglutamine and polyalanine tracts. Moreover, our data suggest that geldanamycin effects on PHOX2B aggregates may be also mediated by the proteasome pathway. Finally, analysis of cellular toxicity due to polyalanine aggregates has confirmed the occurrence of cell apoptosis consequent to expression of PHOX2B carrying the longest expanded alanine tract and shown that geldanamycin can delay cell progression toward the most advanced apoptotic stages.

Bachetti, T., S. Borghini, et al. (2005). "An in vitro approach to test the possible role of candidate factors in the transcriptional regulation of the RET proto-oncogene." GENE EXPRESSION 12(3): 137-49.

Neural crest cells arise from the epithelium of the dorsal neural tube and migrate to various districts giving origin, among others, to sympathetic, parasympathetic, and enteric ganglia. It has been shown that the transcription factors HOX11L1, HOX11L2, MASH1, PHOX2A, and PHOX2B are all necessary, to various extents, to the correct development of the autonomic nervous system. To investigate their possible role in the transcriptional regulation of the RET proto-oncogene, a gene playing a crucial role in correct intestinal innervation, we undertook a specific in vitro experimental strategy. Two neuroblastoma cell lines (SK-N-MC and SK-N-BE) were cotransfected with each transcription factor expressing plasmids and sequential deletion constructs of the 5' c-RET flanking region cloned upstream of the Luciferase reporter gene. Here we show that HOX11L1 enhances the activity of the c-RET promoter in SK-N-MC cell line by stimulating a region between -166 bp and -35 bp. Gel shift assays performed with oligonucleotides spanning this promoter sequence showed a change of the SP1 interaction with its binding sites, consequent to transfection with HOX11L1. While HOX11L2 showed no effect in both the cell lines, we have observed PHOX2A, PHOX2B, and MASH1 triggering a reproducible increase in the Luciferase activity in SK-N-BE cell line. A sequence responsible of the PHOX2A-dependent activation has been identified, while PHOX2B seems to act indirectly, as no physical binding has been demonstrated on c-RET promoter.

Bachetti, T., I. Matera, et al. (2005). "Distinct pathogenetic mechanisms for PHOX2B associated polyalanine expansions and frameshift mutations in congenital central hypoventilation syndrome." HUMAN MOLECULAR GENETICS 14(13): 1815-24.

Congenital central hypoventilation syndrome (CCHS) is a rare neurocristopathy characterized by absence of adequate autonomic control of respiration with decreased sensitivity to hypoxia and hypercapnia. Frameshift mutations and polyalanine triplet expansions in the coding region of PHOX2B have been identified in the vast majority of CCHS patients and a correlation between length of the expanded region and severity of CCHS has been reported. In this work, we have undertaken in vitro analyses aimed at identifying the pathogenetic mechanisms which underlie the effects of PHOX2B mutations in CCHS. According to the known role of this gene, a transcription factor expressed during autonomic nervous system development, we have tested the transcriptional activity of WT and mutant PHOX2B expression constructs on the regulatory regions of two target genes, DbetaH and PHOX2A. We observed that the two sets of mutations play different roles in the transcriptional regulation of these genes, showing a correlation between the length of polyalanine expansions and the severity of reduced transcriptional activity. In particular, although reduced transactivation due to polyalanine expansions may be caused by retention of the mutated protein in the cytoplasm or in the nuclear aggregates, frameshift mutations did not impair the PHOX2B nuclear income, suggesting a different mechanism through which they would exert the observed effects on target promoters. Moreover, the frameshift due to deletion of a cytosine residue seems to cause sequestration of the corresponding mutant PHOX2B in the nucleolar compartment.

Bachetti, T., A. Robbiano, et al. (2006). "Brainstem anomalies in two patients affected by congenital central hypoventilation syndrome." AMERICAN JOURNAL OF RESPIRATORY & CRITICAL CARE MEDICINE 174(6): 706-9.

Congenital central hypoventilation syndrome (CCHS) is a rare neurocristopathy characterized by absence of automatic control of respiration; decreased sensibility to hypoxia and hypercapnia, mainly during sleep; and autosomal dominant inheritance due to heterozygous polyalanine expansions and frameshift mutations in the PHOX2B gene. Because the CCHS phenotype could hide other neurologic diseases, the American Thoracic Society established that the initial evaluation of suspected CCHS should exclude neuroanatomic impairments as the structural basis of the reduced autonomic system function. In this work, we describe the clinical history of two unrelated patients with hypoventilation during sleep and harboring hypoplasia of the pons and a Chiari I malformation, respectively. In both patients, CCHS was diagnosed by detection of PHOX2B polyalanine expansion, suggesting that the American Thoracic Society diagnostic criteria may be too restrictive. Moreover, to exclude a putative role of PHOX2B in non-CCHS neurologic diseases, we have performed PHOX2B mutation screening in a group of individuals with Chiari I malformation, confirming the exclusive role of PHOX2B in the pathogenesis of CCHS.

Bajaj, R., J. Smith, et al. (2005). "Congenital central hypoventilation syndrome and Hirschsprung's disease in an extremely preterm infant." PEDIATRICS 115(6): e737-8.

Congenital central hypoventilation syndrome with Hirschsprung's disease, also known as Haddad syndrome, is a rare disorder with a variable phenotypic severity. The underlying cause is thought to be an abnormality of neural crest development and/or migration. Surviving neonates can have generalized autonomic nervous system dysfunction. Recent reports have identified mutations in the PHOX2B gene in a significant number of patients with this disorder. Diagnosis and management of this disorder in the setting of extreme prematurity is difficult as the manifestations of failure to maintain breathing effort and failure to establish feeds overlap with the complications of prematurity. We describe an infant who had congenital central hypoventilation syndrome with Hirschsprung's disease and was delivered at 26 weeks' gestational age and had total aganglionosis of the bowel, failure to wean from ventilation, and a mutation in the PHOX2B gene.

Balaji, S. (2008). "Sudden death in congenital central hypoventilation syndrome." PEDIATRIC PULMONOLOGY 43(12): 1252; author reply 1253.

Balbir, A., H. Lee, et al. (2007). "A search for genes that may confer divergent morphology and function in the carotid body between two strains of mice." American Journal of Physiology - Lung Cellular and Molecular Physiology 292(3): L704-L715.

The carotid body (CB) is the primary hypoxic chemosensory organ. Its hypoxic response appears to be genetically controlled. We have hypothesized that: 1) genes related to CB function are expressed less in the A/J mice (low responder to hypoxia) compared with DBA/2J mice (high responder to hypoxia); and 2) gene expression levels of morphogenic and trophic factors of the CB are significantly lower in the A/J mice than DBA/2J mice. This study utilizes microarray analysis to test these hypotheses. Three sets of CBs were harvested from both strains. RNA was isolated and used for global gene expression profiling (Affymetrix Mouse 430 v2.0 array). Statistically significant gene expression was determined as a minimum six counts of nine pairwise comparisons, a minimum 1.5-fold change, and P [less-than or equal to] 0.05. Our results demonstrated that 793 genes were expressed less and that 568 genes were expressed more in the A/J strain vs. the DBA/2J strain. Analysis of individual genes indicates that genes encoding ion channels are differentially expressed between the two strains. Genes related to neurotransmitter metabolism, synaptic vesicles, and the development of neural crest-derived cells are expressed less in the A/J CB vs. the DBA/2J CB. Through pathway analysis, we have constructed a model that shows gene interactions and offers a roadmap to investigate CB development and hypoxic chemosensing/chemotransduction processes. Particularly, Gdnf, Bmp2, Kcnmb2, Tph1, Hif1a, and Arnt2 may contribute to the functional differences in the CB between the two strains. Bmp2, Phox2b, Dlx2, and Msx2 may be important for the morphological differences. Copyright copyright 2007 the American Physiological Society.
Barber, M. D. and W. G. Scobie (1995). "Cases of Ondine's curse and Hirschsprung's disease." JOURNAL OF PEDIATRIC SURGERY 30(10): 1531.

Barratt, S., A. H. Kendrick, et al. (2007). "Central hypoventilation with PHOX2B expansion mutation presenting in adulthood." THORAX 62(10): 919-20.

Congenital central hypoventilation syndrome most commonly presents in neonates with sleep related hypoventilation; late onset cases have occurred up to the age of 10 years. It is associated with mutations in the PHOX2B gene, encoding a transcription factor involved in autonomic nervous system development. The case history is described of an adult who presented with chronic respiratory failure due to PHOX2B mutation-associated central hypoventilation and an impaired response to hypercapnia.
Bassani, D. G., C. V. Padoin, et al. (2009). "Estimating the number of children exposed to parental psychiatric disorders through a national health survey." Child & Adolescent Psychiatry & Mental Health [Electronic Resource] 3(1): 6.

ABSTRACT: OBJECTIVE: Children whose parents have psychiatric disorders experience an increased risk of developing psychiatric disorders, and have higher rates of developmental problems and mortality. Assessing the size of this population is important for planning of preventive strategies which target these children. METHODS: National survey data (CCHS 1.2) was used to estimate the number of children exposed to parental psychiatric disorders. Disorders were diagnosed using the World Psychiatric Health Composite International Diagnostic Interview (WMH-CIDI) (12 month prevalence). Data on the number of children below 12 years of age in the home, and the relationship of the respondents with the children, was used to estimate exposure. Parent-child relations were identified, as was single parenthood. Using a design-based analysis, the number of children exposed to parental psychiatric disorders was calculated. RESULTS: Almost 570,000 children under 12 live in households where the survey respondent met criteria for one or more mood, anxiety or substance use disorders in the previous 12 months, corresponding to 12.1% of Canadian children under the age of 12. Almost 3/4 of these children have parents that report receiving no mental health care in the 12 months preceding the survey. For 17% of all Canadian children under age 12, the individual experiencing a psychiatric disorder is the only parent in the household. CONCLUSION: The high number of children exposed causes major concern and has important implications. Although these children will not necessarily experience adversities, they possess an elevated risk of accidents, mortality, and of developing psychiatric disorders. We expect these estimates will promote further research and stimulate discussion at both health policy and planning tables.

Bates, M. D., D. T. Dunagan, et al. (2006). "The Hlx homeobox transcription factor is required early in enteric nervous system development." BMC Developmental Biology 6(33).

Background: Development of the enteric nervous system (ENS) requires interactions between migrating neural crest cells and the nascent gastrointestinal tract that are dependent upon genes expressed by both cell compartments. Hlx, a homeobox transcription factor gene that is expressed in mouse intestinal and hepatic mesenchyme, is required for normal embryonic growth of intestine and liver, and the Hlx^-/- genotype is embryonic lethal. We hypothesized that Hlx is required for ENS development. Results: Enteric neurons were identified in Hlx^+/+ and Hlx^-/- mouse embryos by immunostaining of embryo sections for the neural markers PGP9.5 and Phox2b, or by staining for beta-galactosidase in whole-mount embryos containing the dopamine beta-hydroxylase-nLacZ transgene. In Hlx^+/+ embryos, neural crest cells/enteric neurons have moved from the stomach into the intestine by E10.5. By contrast, neural crest cells/enteric neurons remain largely restricted to the lateral stomach mesenchyme of Hlx^-/- embryos, with only a few scattered neural crest cells/enteric neurons in the intestine between E10.5-16.5. Conclusion: The Hlx homeobox transcription factor is required for early aspects of ENS development. copyright 2006 Bates et al; licensee BioMed Central Ltd.

Beal, M. F., E. P. Richardson, Jr., et al. (1983). "Localized brainstem ischemic damage and Ondine's curse after near-drowning." NEUROLOGY 33(6): 717-21.

A 19-year-old man was a victim of near-drowning in fresh water. After he was resuscitated, examination showed nystagmus, absent gag reflex, diminished facial sensation, dysmetria of all limbs, and failure of automatic respiration. His intellect was perfectly preserved. Eight months later, he died suddenly, and the essential neuropathologic findings were limited to the lower brainstem. There was marked neuronal depletion bilaterally in the nucleus gracilis, nucleus cuneatus, nucleus of the tractus solitarius, nucleus ambiguus, and nucleus retroambiguus; several other lower-brainstem nuclei showed evidence of damage, but to lesser extent. The neuropathologic findings seem to have been an unusual consequence of anoxia-ischemia and support previous concepts of the anatomical localization of the human respiratory centers.

Beamish, D. and J. A. Wildsmith (1978). "Ondine's curse after carotid endarterectomy." BRITISH MEDICAL JOURNAL 2(6152): 1607-8.

Beaufils, F., H. Trang-Pham, et al. (1999). "[Congenital central alveolar hypoventilation syndrome, so-called "Ondine syndrome": an orphan disease, a disease of hope]." ARCHIVES DE PEDIATRIE 6(4): 383-5.

Beck, C. A., S. B. Patten, et al. (2005). "Antidepressant utilization in Canada." Social Psychiatry & Psychiatric Epidemiology 40(10): 799-807.

OBJECTIVE: Antidepressant utilization can be used as an indicator of appropriate treatment for major depression. The objective of this study was to characterize antidepressant utilization in Canada, including the relationships of antidepressant use with sociodemographic variables, past-year and lifetime depression, number of past depressive episodes, and other possible indications for antidepressants. METHOD: We examined data from the Canadian Community Health Survey (CCHS) Cycle 1.2. The CCHS was a nationally representative mental health survey (N=36,984) conducted in 2002 that included a diagnostic instrument for past-year and lifetime major depressive episodes and other psychiatric disorders and a record of past-year antidepressant use. RESULTS: Overall, 5.8% of Canadians were taking antidepressants, higher than the annual prevalence of major depressive episode (4.8%) in the survey. Among persons with a past-year major depressive episode, the frequency of antidepressant use was 40.4%. After application of adjustments for probable successful outcomes of treatment, the estimated frequency of antidepressant use for major depression was more than 50%. Frequency of antidepressant treatment among those with a history of depression but without a past-year episode increased with the number of previous episodes. Among those taking antidepressants over the past year, only 33.1% had had a past-year episode of major depression. Migraine, fibromyalgia, anxiety disorder, or past depression was present in more than 60% of those taking antidepressants without a past-year episode of depression. CONCLUSIONS: The CCHS results suggest that antidepressant use has increased substantially since the early 1990s, and also that these medications are employed extensively for indications other than depression.

Beck, C. A., J. V. A. Williams, et al. (2005). "Psychotropic medication use in Canada." Canadian Journal of Psychiatry - Revue Canadienne de Psychiatrie 50(10): 605-13.

BACKGROUND: Psychotropic medication use can be employed as an indicator of appropriate treatment for mental disorders. The Canadian Community Health Survey: Mental Health and Well-Being (CCHS 1.2) offers the first opportunity to characterize Canadian psychotropic medication use on a national level within diagnostic groups as assessed by a full version of the Composite International Diagnostic Interview (CIDI). METHOD: We assessed the prevalence of antidepressant, sedative-hypnotic, mood stabilizer, psychostimulant, and antipsychotic use over 2 days overall and in subgroups defined by CIDI-diagnosed disorders and demographics. We employed sampling weights and bootstrap methods. RESULTS: Overall psychotropic drug utilization was 7.2%. Utilization was higher for women and with increasing age. With any lifetime CIDI-diagnosed disorder assessed in the CCHS 1.2, utilization was 19.3%, whereas without such disorders, it was 4.1%. Selective serotonin reuptake inhibitors (SSRIs) were the most commonly used antidepressants for those with a past-year major depressive episode (17.8%), followed by venlafaxine (7.4%). Among people aged 15 to 19 years, antidepressant use was 1.8% overall and 11.7% among those with past-year depression; SSRIs made up the majority of use. Sedative-hypnotics were used by 3.1% overall, increasing with age to 11.1% over 75 years. CONCLUSIONS: International comparison is difficult because of different evaluation methods, but antidepressant use may be higher and antipsychotic use lower in Canada than in recent European and American reports. In light of the relative lack of contemporary evidence for antidepressant efficacy in adolescents, it is likely that antidepressant use among those aged 15 to 19 years will continue to decline. The increased use of sedative-hypnotics with age is of concern, given the associated risk of adverse effects among seniors.

Becker, L. E. and S. Takashima (1985). "Chronic hypoventilation and development of brain stem gliosis." NEUROPEDIATRICS 16(1): 19-23.

Chronic hypoventilation is important in the pathogenesis of congenital hypoventilation syndromes and sudden infant death syndrome. Cases of hypoventilation can be divided clinically into those with a defective respiratory drive and those with mechanical impairment of either the lungs or the chest wall. To determine the relationship between chronic hypoventilation and brain stem gliosis, the development of astrocytes in the brain stem of normal and abnormal cases with either type of chronic hypoventilation was studied morphometrically. The glial fibrillary acidic protein immunoperoxidase method of staining astrocytes showed a transient increase of astrocytes in some parts of the brain stem during early infancy in thirty-five normal cases. The astrocytosis was even greater in both types of chronic hypoventilation including subjects with myopathy, Ondine's curse, and sudden infant death syndrome. Gliosis in these subjects may have resulted from "asphyxia" of the brain stem, as seen in cases with myopathies involving respiratory muscles. However, the involvement of brain stem respiratory centers may suggest a failure of neural respiratory control that further compromises respiratory function.

Becker-Christensen, F. G. (2006). "[A child with apnoea]." TIDSSKRIFT FOR DEN NORSKE LAEGEFORENING 126(7): 921-3.

This is a case report of a girl, from the age 73 days to 5 years and 173 days , who during sleep had 127 episodes of apnoea (lasting 20-55 seconds) accompanied by colour shifts. In her first year of life she had 21 episodes of apnoea, in the second 21, in the third 36, in the fourth 22, in the fifth year 7, and during the first 6 months of the sixth year there were 2 episodes of apnoea. An explanation was never found in spite of investigations aiming at cardiopulmonary, neurological or metabolic disease. The staff never verified episodes of apnoea during admittances to hospital wards. The episodes were merely observed by the mother, the father and the grandmother, but the circumstances were persuasive. In addition to episodes of apnoea she had symptoms of dysfunction of the autonomous nervous system, i.e. facial colour shift and sweating without apnoea or exercise. She had frequent attacks of abdominal colic until aged two and a half years. It has not been possible to give a clear-cut diagnosis. It is hypothesized that she suffers from a mild form of a disease entity covering a wide spectrum from Ondine's curse (Congenital central hypoventilation syndrome) to remittent Apparent life-threatening events (ALTEs) and Sudden infant death syndrome (SIDS).

Beckerman, R., J. Meltzer, et al. (1986). "Brain-stem auditory response in Ondine's syndrome." ARCHIVES OF NEUROLOGY 43(7): 698-701.

Brain-stem auditory evoked responses were measured during sleep in four infants with congenital central alveolar hypoventilation syndrome (Ondine's syndrome) and four controls matched for age and sex. Delays in peak latencies p III and interpeak latencies p I-III were consistently seen in these patients but not in the control children. These abnormalities were reproducible and suggested disruption in the normal auditory pathways at the level of the mid to upper brain stem through which fibers pass close to the area of respiratory control. These abnormalities, both electrophysiologic and metabolic, imply a functional disturbance of brain-stem control of ventilation during sleep in infants and children suffering from Ondine's syndrome.

Beckerman, R. C. (1997). "Home positive pressure ventilation in congenital central hypoventilation syndrome: More than twenty years of experience." PEDIATRIC PULMONOLOGY 23(2): 154-155.

Beede, H. E. and R. W. Newcomb (1980). "Lower motor neuron paralysis in association with asthma." Johns Hopkins Medical Journal 147(5): 186-187.

Since 1968 a peculiar flaccid paralysis has been recognized in some children recovering from episodes of asthma. Originally reported from Australia, it has also been encountered in Great Britain, Seattle, Sweden, and again in Australia. The authors report here the second case from the United States.
Beland, Y. (2002). "Canadian community health survey--methodological overview." HEALTH REPORTS 13(3): 9-14.

OBJECTIVES: This article describes the design, sampling strategy, interviewing procedures, data collection and processing of the Canadian Community Health Survey (CCHS). SUMMARY: Data collection for cycle 1.1 of the CCHS began in September 2000. This first cycle provides cross-sectional data at the regional level for 136 health regions; the first half of data collected for cycle 1.1 provides data for 133 health regions. In addition to the survey methods, this article reports the sample size and rates of proxy response and non-response for each province, for the first six months of cycle 1.1. A summary of methods used to impute values that were not provided by proxy respondents is provided. A discussion of survey errors and their sources follows.