Literature search from ms 29/4/2010

Hennewig, U., B. Hadzik, et al. (2008). "Congenital central hypoventilation syndrome with hyperinsulinism in a preterm infant." Journal of Human Genetics 53(6): 573-7.

Congenital central hypoventilation syndrome (CCHS), a rare disorder typically presenting in the newborn period, results in over 90% of cases from PHOX2B polyalanine repeat mutations. It is characterized by alveolar hypoventilation, symptoms of autonomic nervous system dysregulation, and in a subset of cases Hirschsprung's disease and, later, tumors of neural crest origin. We describe a preterm infant with severe phenotype of CCHS and hyperinsulinism. A novel de novo heterozygote missence mutation (Gly68Cys) in the PHOX2B gene could be identified. Based on the observation of three patients presenting with the combination of congenital hyperinsulinism and CCHS, hyperinsulinism might represent an additional clinical feature of CCHS.

Hermann, P. M. and C. C. Logan (2003). "Electroporation of proviral RCAS DNA alters gene expression in the embryonic chick hindbrain." BIOTECHNIQUES 35(5): 942-949.

Gene transfer by means of electroporation is an effective method for delivering DNA into cells. Expression vectors encoding green fluorescent protein (GFP) are routinely used as a control for this technique and are also regularly used to indirectly or directly monitor the expression of introduced transgenes. However, recent studies suggest that GFP may have nonspecific and/ or cytotoxic side effects. In this study, we investigated the effects of enhanced GFP (EGFP) expression delivered by means of electroporation of proviral RCASBP(B)-EGFP DNA on gene expression in the hindbrain of chick embryos. We examined, via whole-mount in situ hybridization, the expression of a number of transcription factors. We found that Tlx-1 was ectopically expressed following electroporation of proviral RCASBP(B)-EGFP DNA. In contrast, the number of cells expressing Tlx-3, Phox2a, and Phox2b were reduced. Intriguingly, these effects could be mimicked by electroporation of wild-type proviral RCASBP(B) DNA (i.e., lacking the GFP insert). However, neither delivery of the EGFP transgene by means of viral infection nor electroporation alone yielded aberrant expression patterns. Together our data indicate that alterations of gene expression patterns are not directly due to the expression of EGFP but instead reflect a confounding effect of electroporating proviral DNA.

Hernandez-Perez, E. and R. Cestoni-Parducci (1985). "Nodular hidradenoma and hidradenocarcinoma. A 10-year review." JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY 12(1 Pt 1): 15-20.

We studied eighty-nine nodular hidradenomas (NHs) and six clear cell hidradenocarcinomas (CCHs) reported in a 10-year period. NHs were more commonly seen in women (ratio of 1.7 to 1); the average age was 37.2 years, and they were located mainly on the head. One CCH had widely disseminated metastasis that led to death. Other CCHs underwent spontaneous regression.

Hiraishi, T., T. Kawaguchi, et al. (1984). "[A case report of central alveolar hypoventilation syndrome (Ondine's curse)]." Masui - Japanese Journal of Anesthesiology 33(2): 183-8.

Hirsch, M. R., J. C. Glover, et al. (2007). "Forced expression of Phox2 homeodomain transcription factors induces a branchio-visceromotor axonal phenotype." DEVELOPMENTAL BIOLOGY 303(2): 687-702.

What causes motor neurons to project into the periphery is not well understood. We here show that forced expression of the homeodomain protein Phox2b, shown previously to be necessary and sufficient for branchio-visceromotor neuron development, and of its paralogue Phox2a imposes a branchiomotor-like axonal phenotype in the spinal cord. Many Phox2-transfected neurons, whose axons would normally stay within the confines of the neural tube, now project into the periphery. Once outside the neural tube, a fraction of the ectopic axons join the spinal accessory nerve, a branchiomotor nerve which, as shown here, does not develop in the absence of Phox2b. Explant studies show that the axons of Phox2-transfected neurons need attractive cues to leave the neural tube and that their outgrowth is promoted by tissues, to which branchio-visceromotor fibers normally grow. Hence, Phox2 expression is a key step in determining the peripheral axonal phenotype and thus the decision to stay within the neural tube or to project out of it. copyright 2006 Elsevier Inc. All rights reserved.
Ho, H.-T., P. Thajeb, et al. (2005). "Ondine's curse in a patient with unilateral medullary and bilateral cerebellar infarctions." Journal of the Chinese Medical Association: JCMA 68(11): 531-4.

Central sleep apnea (CSA), also known as Ondine's curse (OC), is a phenomenon characterized by episodes of repeated apnea during sleep due to disorders of the central nervous system. We report a patient with CSA/OC due to right dorsolateral medullary and bilateral cerebellar infarctions that occurred in the clinical setting of right vertebral artery stenosis. Polysomnography (PSG) showed repeated episodes of absence of nasal cannula flow accompanying cessation of thoracic and abdominal respiratory movements and a decline in blood oxygen saturation. The duration of apnea was as long as 12 seconds. Brain magnetic resonance (MR) images showed acute infarctions involving the right dorsolateral medulla, bilateral cerebellar vermis and paramedian cerebellar hemispheres. MR angiography showed nonvisualization of the right vertebral artery. Transcranial Doppler sonography showed a high resistance flow profile in the right vertebral artery and normal flow patterns in the basilar artery and left vertebral artery. These findings suggest that the medullary and bilateral cerebellar infarcts were caused by stenosis/pseudo-occlusion of the right vertebral artery. Reduced respiratory afferent inputs to the dorsal respiratory group of medullary neurons, the nucleus tractus solitarius and reduced "automatic" components of the respiratory drive may play a role in the development of CSA/OC.

Hok, B., L. Wiklund, et al. (1993). "A new respiratory rate monitor: development and initial clinical experience." International Journal of Clinical Monitoring & Computing 10(2): 101-7.

The need for continuous, noninvasive, and reliable respiratory rate monitoring during recovery from general anesthesia has long been recognized. Alternative principles can be grouped into those detecting the respiratory effort, and those detecting the actual result, i.e. the respiratory gas flow. The second category is of greatest interest for patient monitoring. In this paper, we report the development and initial clinical experience with a new acoustic air-flow sensor. By differential, multipoint detection of the air-flow in the mouth and nose region, the sensor can easily discriminate against different kinds of interference, including motion artefacts. The sensor is nonexpensive, rugged, simple to apply and inherently safe. An instrument with continuous display of respiratory rate, and an audiovisual apnea alarm has been designed and built. The complete system has been tested on patients during recovery after general anesthesia. In 16 patients, the respiratory rate displayed by the instrument has been correlated against that visually observed. A good correlation was obtained. Minor discrepancies can be explained from the fact that visual observation corresponds to the respiratory effort, whereas the sensor detects the actual air flow. In 12 patients, 24 hour simultaneous recordings were made of respiratory rate with the new sensor, with simultaneous recording of the oxygen saturation and the heart rate with a pulse oximeter. It was found that the new sensor reliably recorded respiratory depression and apnea. Such events may in some patients be as frequent as one incident per hour. One case of 'Ondine's curse' provided clear evidence that pulse oximetry has a low sensitivity to respiratory disorders.

Hok, B., L. Wiklund, et al. (1994). "A new respiratory rate monitor: development and initial clinical experience reprinted from the International Journal of Clinical Monitoring and Computing 10: 101-107, 1993." Neonatal Intensive Care 7(2): 24-8.

The need for continuous, noninvasive, and reliable respiratory rate monitoring during recovery from general anesthesia has long been recognized. Alternative principles can be grouped into those detecting the respiratory effort, and those detecting the actual results, ie the respiratory gas flow. The second category is of greatest interest for patient monitoring. In this paper, we report the development and initial clinical experience with a new air-flow sensor. By differential, multipoint detection of the air flow in the mouth and nose region, the sensor can easily discriminate against different kinds of interference, including motion artefacts. The sensor is nonexpensive, rugged, simple to apply, and inherently safe. An instrument with continuous display of respiratory rate, and an audiovisual apnea alarm has been designed and built. The complete system has been tested on patients during recovery after general anesthesia. In 16 patients, the respiratory rate displayed by the instrument has been correlated against that visually observed. A good correlation was obtained. Minor discrepancies can be explained from the fact that visual observation corresponds to the respiratory effect, whereas the sensor detects the actual air flow. In 12 patients, 24 hour simultaneous recordings were made of respiratory rate with the new sensor, with simultaneous recording of the oxygen saturation and the heart rate with a pulse oximeter. It was found that the new sensor reliably recorded respiratory depression and apnea. Such events may in some patients be as frequent as one incident per hour. One case of "Ondine's curse" provided clear evidence that pulse oximetry has a low sensitivity to repsiratory disorders.

Holzemer, S. (1995). "CCHS confronts issues in community-based and managed care Council of Community Health Services." NLN Update 1(1): 5.

Holzinger, A., R. A. Mittal, et al. (2005). "A novel 17 bp deletion in the PHOX2B gene causes congenital central hypoventilation syndrome with total aganglionosis of the small and large intestine." AMERICAN JOURNAL OF MEDICAL GENETICS Part A. 139(1): 50-1.

Hon, E. K., M. Wilson, et al. (1994). "The survival story of a child with Ondine's curse in Northland." NEW ZEALAND MEDICAL JOURNAL 107(976): 149-50.

The case of a six year old European male with congenital central hypoventilation is reported to illustrate that survival and positive developmental outcome is possible in a remote town in the Northland. Initial and ongoing problems include persistent ventilatory requirement, medical, developmental and psychosocial issues. Positive parental attitude, meticulous care to activities of daily living, medical and psychosocial surveillance and continuing support contribute to the success in management. Various treatment options are also discussed. Primary failure of respiratory regulation, also known as congenital central hypoventilation or Ondine's curse, has been infrequently reported in children. Survival and positive developmental outcome is possible but requires intensive support and positive parental attitude, as well as parental education and ongoing medical and psychosocial surveillance. We report this case to illustrate that this could be achieved even in a remote country town.

Hong, S. J., H. Chae, et al. (2008). "Trim11 increases expression of dopamine beta-hydroxylase gene by interacting with Phox2b." Biochemical & Biophysical Research Communications 368(3): 650-5.

The homeodomain transcription factor Phox2b is one of the key determinants involved in the development of noradrenergic (NA) neurons in both the central nervous system (CNS) and the peripheral nervous system (PNS). Using yeast two-hybrid screening, we isolated a Phox2b interacting protein, Trim11, which belongs to TRIM (Tripartite motif) or RBCC proteins family, and contains a RING domain, B-boxes, a coiled-coil domain, and the B30.2/SPRY domain. Protein-protein interaction assays showed that Phox2b was able to physically interact with Trim11. The B30.2/SPRY domain of Trim11 was required for the interaction with Phox2b. Expression of Phox2b and Trim11 was detected in the sympathetic ganglia (SG) of mouse embryos. Forced expression of Trim11 with Phox2b further increased mRNA levels of dopamine beta-hydroxylase (DBH) gene in primary avian neural crest stem cell (NCSC) culture. This study suggests a potential role for Trim11 in the specification of NA phenotype by interaction with Phox2b.

Hong, S. J., C. H. Kim, et al. (2001). "Structural and functional characterization of the 5' upstream promoter of the human Phox2a gene: possible direct transactivation by transcription factor Phox2b." JOURNAL OF NEUROCHEMISTRY 79(6): 1225-36.

The specification of neurotransmitter identity is a critical step in neural development. Recent progresses have indicated that the closely related homeodomain factors Phox2a and 2b are essential for development of noradrenergic (NA) neuron differentiation, and may directly determine the neurotransmitter identity. With a long-term goal of understanding the regulatory cascade of NA phenotype determination, we isolated and characterized a hPhox2a genomic clone encompassing approximately 7.5 kb of the 5' upstream promoter region, the entire exon-intron structure, and approximately 4 kb of the 3' flanking region. Using mRNAs isolated from the Phox2a-expressing human cell line, both primer extension and 5'-rapid amplification of cDNA ends analyses identified a single transcription start site that resides 172 nucleotides upstream of the start codon. The transcription start site was preceded by a TATA-like sequence motif and transcripts from this site contained an additional G residue at the 5' position, supporting the authenticity of this site as the transcriptional start site of hPhox2a. We assembled hPhox2a-luciferase reporter constructs containing different lengths of the 5' upstream sequences. Transient transfection assays of these reporter constructs in both hPhox2a-positive and -negative cell lines show that 1.3-kb or longer upstream sequences of the hPhox2a gene may confer NA cell-specific reporter gene expression. Furthermore, cotransfection assays in the Phox2a-negative HeLa cell line show that forced expression of Phox2b, but not that of Phox2a or MASH1, significantly transactivates the transcriptional activity of hPhox2a. This study will provide a frame to further delineate the regulatory cascade of NA neuron differentiation.

Hopkins, R. B., R. Goeree, et al. (2010). "Estimating the national wage loss from cancer in Canada." CURRENT ONCOLOGY 17(2): 40-9.

OBJECTIVES: Using primary and secondary data sources, we set out to estimate the Canadian wage loss from cancer for patients, caregivers, and parents from a patient and a societal perspective. METHODS: First, a multiple-database literature search was conducted to find Canadian-specific direct surveys of wage loss from cancer. Second, estimates for wage loss were generated from the nationally representative Canadian Community Health Survey (cchs) Cycle 3.1. In addition, both estimates were standardized to derive a friction-period estimate and were extrapolated to produce national annual estimates. RESULTS: The literature search identified six direct surveys that included a total of 1632 patients with cancer. The cchs Cycle 3.1 included 2287 patients with cancer. Overall, based on the direct surveys, newly diagnosed cancer patients reduced their labour participation in the friction period by 36% ($4,518), and caregivers lost 23% of their workable hours ($2,887). The cchs estimated that annual household income was 26.5% lower ($4,978) for respondents with cancer as compared with the general population. For the year 2009, results from direct surveys indicated that new cancers in Canada generated a wage loss of $3.18 billion; the cchs Cycle 3.1 estimate was $2.95 billion. CONCLUSIONS: Wage loss from cancer is a significant economic burden on patients, their families, and society in Canada, with direct surveys and the cchs providing similar estimates.

Horiuchi, H., A. Sasaki, et al. (2005). "Sensitive detection of polyalanine expansions in PHOX2B by polymerase chain reaction using bisulfite-converted DNA." Journal of Molecular Diagnostics 7(5): 638-40.

Congenital central hypoventilation syndrome, also known as Ondine's curse, is characterized by idiopathic abnormal control of respiration during sleep. Recent studies indicate that a polyalanine expansion of PHOX2B is relevant to the pathogenesis of this disorder. However, it is difficult to detect the repeated tract because its high GC content inhibits conventional polymerase chain reaction (PCR) amplification. Here, we describe a bisulfite treatment for DNA in which uracil is obtained by deamination of unmethylated cytosine residues. Deamination of DNA permitted direct PCR amplification that yielded a product of 123 bp for the common 20-residue repetitive tract with replacement of C with T by sequencing. It settled allele dropouts accompanied by insufficient amplification of expanded alleles. The defined procedure dramatically improved detection of expansions to 9 of 10 congenital central hypoventilation syndrome patients examined in a previous study. The chemical conversion of DNA before PCR amplification facilitates effective detection of GC-rich polyalanine tracts.

Howard, M. J., M. Stanke, et al. (2000). "The transcription factor dHAND is a downstream effector of BMPs in sympathetic neuron specification." DEVELOPMENT 127(18): 4073-4081.

The dHAND basic helix-loop-helix transcription factor is expressed in neurons of sympathetic ganglia and has previously been shown to induce the differentiation of catecholaminergic neurons in avian neural crest cultures. We now demonstrate that dHAND expression is sufficient to elicit the generation of ectopic sympathetic neurons in vivo. The expression of the dHAND gene is controlled by bone morphogenetic proteins (BMPs), as suggested by BMP4 overexpression in vivo and in vitro, and by noggin-mediated inhibition of BMP function in vivo. The timing of dHAND expression in sympathetic ganglion primordia, together with the induction of dHAND expression in response to Phox2b implicate a role for dHAND as transcriptional regulator downstream of Phox2b in BMP-induced sympathetic neuron differentiation.

Hoyer, A. P., A.-M. Gerdes, et al. (2002). "Organochlorines, p53 mutations in relation to breast cancer risk and survival. A Danish cohort-nested case-controls study." Breast Cancer Research & Treatment 71(1): 59-65.

Epidemiological studies integrating genetic susceptibility with biological measurements of organochlorine exposure may provide new clues regarding these substances influence on breast cancer etiology. Initial attempts pursuing this avenue has dealt with polymorphisms in the carcinoge metabolizing enzymes cytochrome P450 (CYP1A1). This study examined if mutations in the tumor suppressor gene p53 affected organochlorine exposure related breast cancer risk and survival. The material consisted of 162 breast cancer cases and 316 matched controls, who had participated, in the Copenhagen City Heart Study (CCHS) between 1976 and 1978. Cases diagnosed between study initiation and 1993 were identified by linkage to the Danish Cancer Registry. The case group served as a cohort in the survival analyses. Information on known and suspected breast cancer risk factors was obtained from CCHS, and the Danish Breast Cancer Cooperative Group provided information on tumor characteristics. Lipid adjusted serum concentrations of selected organochlorines were compared between cases and controls while stratifing by p53 mutation status. A non-significant increased risk of breast cancer was observed in the highest exposure level of dieldrin and polychlorinated biphenyls among women who developed a tumor with mutant p53 (odds ratio (OR) = 3.53, 95% confidence interval (CI) = 0.79-15.79 and OR = 3.00, 95% CI = 0.66-13.62). There was no clear difference in overall survival between breast cancer cases with 'wild-type' and mutant p53, although a significant dose-response relationship appeared for dieldrin exposure in tumors with 'wild-type' p53. These preliminary results suggest that p53 mutations may have a modifying effect on at least the breast cancer risk associated with exposures to organochlorines.

Hoyer, A. P., T. Jorgensen, et al. (2000). "Repeated measurements of organochlorine exposure and breast cancer risk (Denmark)." Cancer Causes & Control 11(2): 177-84.

OBJECTIVE: To prospectively evaluate if repeated measurements of organochlorine exposure provide a more precise measure of breast cancer risk. METHODS: In the Copenhagen City Heart Study (CCHS) participants donated blood twice, in 1976-1978 and 1981 1983. Information on breast cancer risk factors was obtained through standardized questionnaires. A cohort nested case-control study of 155 cases and 274 matched breast cancer-free controls who had participated in both CCHS examinations was conducted. The average serum organochlorine concentration over the course of the two examinations was used, testing a possible association between organochlorine exposure and breast cancer risk. RESULTS: A high serum concentration of p,p'-DDT over the course of the two examinations was associated with a more than three-fold significantly increased risk of breast cancer, and a dose-response relationship was apparent. Furthermore, the risk of breast cancer increased with increasing serum concentrations of PCB congener 118 and 138 and the total amount of DDT isomers (sigmaDDT), but the trends were not significant. CONCLUSION: This study provides new evidence of the adverse effect of some organochlorines on breast cancer risk. Furthermore, repeated assessment of exposure during a relevant time period may provide a more precise risk estimate than a single measurement.

Hu, Y. F., M. G. Caron, et al. (2009). "Norepinephrine transport-mediated gene expression in noradrenergic neurogenesis." BMC Genomics 10(151).

Background: We have identified a differential gene expression profile in neural crest stem cells that is due to deletion of the norepinephrine transporter (NET) gene. NET is the target of psychotropic substances, such as tricyclic antidepressants and the drug of abuse, cocaine. NET mutations have been implicated in depression, anxiety, orthostatic intolerance and attention deficit hyperactivity disorder (ADHD). NET function in adult noradrenergic neurons of the peripheral and central nervous systems is to internalize norepinephrine from the synaptic cleft. By contrast, during embryogenesis norepinephrine (NE) transport promotes differentiation of neural crest stem cells and locus ceruleus progenitors into noradrenergic neurons, whereas NET inhibitors block noradrenergic differentiation. While the structure of NET und the regulation of NET function are well described, little is known about downstream target genes of norepinephrine (NE) transport. Results: We have prepared gene expression profiles of in vitro differentiating wild type and norepinephrine transporter-deficient (NETKO) mouse neural crest cells using long serial analysis of gene expression (LongSAGE). Comparison analyses have identified a number of important differentially expressed genes, including genes relevant to neural crest formation, noradrenergic neuron differentiation and the phenotype of NETKO mice. Examples of differentially expressed genes that affect noradrenergic cell differentiation include genes in the bone morphogenetic protein (BMP) signaling pathway, the Phox2b binding partner Tlx2, the ubiquitin ligase Praja2, and the inhibitor of Notch signaling, Numbl. Differentially expressed genes that are likely to contribute to the NETKO phenotype include dopamine-beta-hydroxylase (Dbh), tyrosine hydroxylase (Th), the peptide transmitter 'cocaine and amphetamine regulated transcript' (Cart), and the serotonin receptor subunit Htr3a. Real-time PCR confirmed differential expression of key genes not only in neural crest cells, but also in the adult superior cervical ganglion and locus ceruleus. In addition to known genes we have identified novel differentially expressed genes and thus provide a valuable database for future studies. Conclusion: Loss of NET function during embryonic development in the mouse deregulates signaling pathways that are critically involved in neural crest formation and noradrenergic cell differentiation. The data further suggest deregulation of signaling pathways in the development and/or function of the NET-deficient peripheral, central and enteric nervous systems. copyright 2009 Hu et al; licensee BioMed Central Ltd.