GLORIA

GEOMAR Library Ocean Research Information Access

X

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    Online Resource
    Online Resource
    Newborn Screening for X-Linked Adrenoleukodystrophy: Review of Data and Outcomes in Pennsylvania
    MDPI AG ; 2022
    In:  International Journal of Neonatal Screening Vol. 8, No. 2 ( 2022-03-23), p. 24-
    Details
    In: International Journal of Neonatal Screening, MDPI AG, Vol. 8, No. 2 ( 2022-03-23), p. 24-
    Abstract: X-linked adrenoleukodystrophy (X-ALD) is the most common peroxisomal disorder. It results from pathogenic variants in ABCD1, which encodes the peroxisomal very-long-chain fatty acid transporter, causing a spectrum of neurodegenerative phenotypes. The childhood cerebral form of the disease is particularly devastating. Early diagnosis and intervention improve outcomes. Because newborn screening facilitates identification of at-risk individuals during their asymptomatic period, X-ALD was added to the Pennsylvania newborn screening program in 2017. We analyzed outcomes from the first four years of X-ALD newborn screening, which employed a two-tier approach and reflexive ABCD1 sequencing. There were 51 positive screens with elevated C26:0-lysophosphatidylcholine on second-tier screening. ABCD1 sequencing identified 21 hemizygous males and 24 heterozygous females, and clinical follow up identified four patients with peroxisomal biogenesis disorders. There were two false-positive cases and one false-negative case. Three unscreened individuals, two of whom were symptomatic, were diagnosed following their young siblings’ newborn screening results. Combined with experiences from six other states, this suggests a U.S. incidence of roughly 1 in 10,500, higher than had been previously reported. Many of these infants lack a known family history of X-ALD. Together, these data highlight both the achievements and challenges of newborn screening for X-ALD.
    Type of Medium: Online Resource
    ISSN: 2409-515X
    URL: Article
    DOI: 10.3390/ijns8020024
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2840820-2
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 2
    Online Resource
    Online Resource
    The Importance of Succinylacetone: Tyrosinemia Type I Presenting with Hyperinsulinism and Multiorgan Failure Following Normal Newborn Screening
    MDPI AG ; 2020
    In:  International Journal of Neonatal Screening Vol. 6, No. 2 ( 2020-05-16), p. 39-
    Details
    In: International Journal of Neonatal Screening, MDPI AG, Vol. 6, No. 2 ( 2020-05-16), p. 39-
    Abstract: Tyrosinemia type I (TT1) is an inborn error of tyrosine metabolism with features including liver dysfunction, cirrhosis, and hepatocellular carcinoma; renal dysfunction that may lead to failure to thrive and bone disease; and porphyric crises. Once fatal in most infantile-onset cases, pre-symptomatic diagnosis through newborn screening (NBS) protocols, dietary management, and pharmacotherapy with nitisinone have improved outcomes. Succinylacetone provides a sensitive and specific marker for the detection of TT1 but is not universally utilized in screening protocols for the disease. Here, we report an infant transferred to our facility for evaluation and management of hyperinsulinism who subsequently developed acute-onset liver, respiratory, and renal failure around one month of life. She was found to have TT1 caused by novel pathogenic variant in fumarylacetoacetate hydrolase (c.1014 delC, p.Cys 338 Ter). Her NBS, which utilized tyrosine as a primary marker, had been reported as normal, with a tyrosine level of 151 µmol/L (reference: 〈 280 µmol/L). Retrospective analysis of dried blood spot samples via tandem mass spectrometry showed detectable succinylacetone ranging 4.65–10.34 µmol/L. To our knowledge, this is the first patient with TT1 whose initial presenting symptom was hyperinsulinemic hypoglycemia. The case highlights the importance of maintaining a high suspicion for metabolic disease in critically ill children, despite normal NBS. We also use the case to advocate for NBS for TT1 using succinylacetone quantitation.
    Type of Medium: Online Resource
    ISSN: 2409-515X
    URL: Article
    DOI: 10.3390/ijns6020039
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2840820-2
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 3
    Online Resource
    Online Resource
    Vascular dysfunction precedes hypertension associated with a blood pressure locus on rat chromosome 12
    American Physiological Society ; 2014
    In:  American Journal of Physiology-Heart and Circulatory Physiology Vol. 307, No. 8 ( 2014-10-15), p. H1103-H1110
    Details
    In: American Journal of Physiology-Heart and Circulatory Physiology, American Physiological Society, Vol. 307, No. 8 ( 2014-10-15), p. H1103-H1110
    Abstract: We previously isolated a 6.1-Mb region of SS/Mcwi (Dahl salt-sensitive) rat chromosome 12 (13.4–19.5 Mb) that significantly elevated blood pressure (BP) (Δ+34 mmHg, P 〈 0.001) compared with the SS-12 BN consomic control. In the present study, we examined the role of vascular dysfunction and remodeling in hypertension risk associated with the 6.1-Mb (13.4–19.5 Mb) locus on rat chromosome 12 by reducing dietary salt, which lowered BP levels so that there were no substantial differences in BP between strains. Consequently, any observed differences in the vasculature were considered BP-independent. We also reduced the candidate region from 6.1 Mb with 133 genes to 2 Mb with 23 genes by congenic mapping. Both the 2 Mb and 6.1 Mb congenic intervals were associated with hypercontractility and decreased elasticity of resistance vasculature prior to elevations of BP, suggesting that the vascular remodeling and dysfunction likely contribute to the pathogenesis of hypertension in these congenic models. Of the 23 genes within the narrowed congenic interval, 12 were differentially expressed between the resistance vasculature of the 2 Mb congenic and SS-12 BN consomic strains. Among these, Grifin was consistently upregulated 2.7 ± 0.6-fold ( P 〈 0.05) and 2.0 ± 0.3-fold ( P 〈 0.01), and Chst12 was consistently downregulated −2.8 ± 0.3-fold ( P 〈 0.01) and −4.4 ± 0.4-fold ( P 〈 0.00001) in the 2 Mb congenic compared with SS-12 BN consomic under normotensive and hypertensive conditions, respectively. A syntenic region on human chromosome 7 has also been associated with BP regulation, suggesting that identification of the genetic mechanism(s) underlying cardiovascular phenotypes in this congenic strain will likely be translated to a better understanding of human hypertension.
    Type of Medium: Online Resource
    ISSN: 0363-6135 , 1522-1539
    URL: Article
    DOI: 10.1152/ajpheart.00464.2014
    RVK:
    WA 15000
    Language: English
    Publisher: American Physiological Society
    Publication Date: 2014
    detail.hit.zdb_id: 1477308-9
    SSG: 12
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 4
    Online Resource
    Online Resource
    The NRF2 knockout rat: a new animal model to study endothelial dysfunction, oxidant stress, and microvascular rarefaction
    American Physiological Society ; 2016
    In:  American Journal of Physiology-Heart and Circulatory Physiology Vol. 310, No. 4 ( 2016-02-15), p. H478-H487
    Details
    In: American Journal of Physiology-Heart and Circulatory Physiology, American Physiological Society, Vol. 310, No. 4 ( 2016-02-15), p. H478-H487
    Abstract: Nuclear factor (erythroid-derived 2)-like-2 (NRF2) is a master antioxidant and cell protective transcription factor that upregulates antioxidant defenses. In this study we developed a strain of Nrf2 null mutant rats to evaluate the role of reduced NRF2-regulated antioxidant defenses in contributing to endothelial dysfunction and impaired angiogenic responses during salt-induced ANG II suppression. Nrf2 −/− mutant rats were developed using transcription activator-like effector nuclease technology in the Sprague-Dawley genetic background, and exhibited a 41-bp deletion that included the start codon for Nrf2 and an absence of immunohistochemically detectable NRF2 protein. Expression of mRNA for the NRF2-regulated indicator enzymes heme oxygenase-1, catalase, superoxide dismutase 1, superoxide dismutase 2, and glutathione reductase was significantly lower in livers of Nrf2 −/− mutant rats fed high salt (HS; 4% NaCl) for 2 wk compared with wild-type controls. Endothelium-dependent dilation to acetylcholine was similar in isolated middle cerebral arteries (MCA) of Nrf2 −/− mutant rats and wild-type littermates fed low-salt (0.4% NaCl) diet, and was eliminated by short-term (3 days) HS diet in both strains. Low-dose ANG II infusion (100 ng/kg sc) reversed salt-induced endothelial dysfunction in MCA and prevented microvessel rarefaction in wild-type rats fed HS diet, but not in Nrf2 −/− mutant rats. The results of this study indicate that suppression of NRF2 antioxidant defenses plays an essential role in the development of salt-induced oxidant stress, endothelial dysfunction, and microvessel rarefaction in normotensive rats and emphasize the potential therapeutic benefits of directly upregulating NRF2-mediated antioxidant defenses to ameliorate vascular oxidant stress in humans.
    Type of Medium: Online Resource
    ISSN: 0363-6135 , 1522-1539
    URL: Article
    DOI: 10.1152/ajpheart.00586.2015
    RVK:
    WA 15000
    Language: English
    Publisher: American Physiological Society
    Publication Date: 2016
    detail.hit.zdb_id: 1477308-9
    SSG: 12
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 5
    Online Resource
    Online Resource
    Clinical spectrum of BCS1L Mitopathies and their underlying structural relationships
    Wiley ; 2019
    In:  American Journal of Medical Genetics Part A Vol. 179, No. 3 ( 2019-03), p. 373-380
    Details
    In: American Journal of Medical Genetics Part A, Wiley, Vol. 179, No. 3 ( 2019-03), p. 373-380
    Abstract: The most frequent cause of isolated complex III deficits is mutations to the nuclear‐encoded ATPase BCS1L . Disease phenotypes are varied and can be as mild as Björnstad syndrome, characterized by pili torti and sensorineural hearing loss, or as severe as GRACILE syndrome, characterized by growth restriction, aminoaciduria, cholestasis, iron overload, lactic acidosis, and early death. BCS1L mutations are also linked to an undefined complex III deficiency, a heterogeneous condition generally involving low birth weight, renal and hepatic pathologies, hypotonia, and developmental delays. We analyzed all published patient cases of mutations to BCS1L and modeled the tertiary and quaternary structure of the BCS1L protein to map the location of disease‐causing BCS1L mutations. We show that higher order structural analysis can be used to understand the phenotype observed in a patient with the novel compound heterozygous c.550C 〉 T(p.Arg184Cys) and c.838C 〉 T(p.Leu280Phe) mutations. More broadly, higher order structural analysis reveals genotype–phenotype relationships within the intermediate complex III deficiency category that help to make sense of the spectrum of observed phenotypes. We propose a change in nomenclature that unifies the intermediate phenotype under “ BCS1L Mitopathies”. Patterns in genotype–phenotype correlations within these BCS1L Mitopathies are evident in the context of the tertiary and quaternary structure of BCS1L.
    Type of Medium: Online Resource
    ISSN: 1552-4825 , 1552-4833
    URL: Issue
    URL: Article
    DOI: 10.1002/ajmg.v179.3
    DOI: 10.1002/ajmg.a.61019
    Language: English
    Publisher: Wiley
    Publication Date: 2019
    detail.hit.zdb_id: 1493479-6
    SSG: 12
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 6
    Online Resource
    Online Resource
    Unmasking the challenges of Kabuki syndrome in adulthood: A case series
    Wiley ; 2023
    In:  American Journal of Medical Genetics Part C: Seminars in Medical Genetics Vol. 193, No. 2 ( 2023-06), p. 128-138
    Details
    In: American Journal of Medical Genetics Part C: Seminars in Medical Genetics, Wiley, Vol. 193, No. 2 ( 2023-06), p. 128-138
    Abstract: Kabuki syndrome is a recognizable Mendelian disorder characterized by the clinical constellation of childhood hypotonia, developmental delay or intellectual impairment, and characteristic dysmorphism resulting from monoallelic pathogenic variants in KMT2D or KDM6A . In the medical literature, most reported patients are children, and data is lacking on the natural history of the condition across the lifespan, with little known about adult‐specific presentations and symptoms. Here, we report the results of a retrospective chart review of eight adult patients with Kabuki syndrome, seven of whom are molecularly confirmed. We use their trajectories to highlight the diagnostic challenges unique to an adult population, expand on neurodevelopmental/psychiatric phenotypes across the lifespan, and describe adult‐onset medical complications, including a potential cancer risk and unusual and striking premature/accelerated aging phenotype.
    Type of Medium: Online Resource
    ISSN: 1552-4868 , 1552-4876
    URL: Issue
    URL: Article
    DOI: 10.1002/ajmg.c.v193.2
    DOI: 10.1002/ajmg.c.32054
    Language: English
    Publisher: Wiley
    Publication Date: 2023
    detail.hit.zdb_id: 2143867-5
    SSG: 12
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 7
    Online Resource
    Online Resource
    NRF 2 activation with Protandim attenuates salt‐induced vascular dysfunction and microvascular rarefaction
    Wiley ; 2019
    In:  Microcirculation Vol. 26, No. 7 ( 2019-10)
    Details
    In: Microcirculation, Wiley, Vol. 26, No. 7 ( 2019-10)
    Abstract: This study tested the hypothesis that dietary activation of the master antioxidant and cell protective transcription factor nuclear factor, erythroid ‐2‐like 2 (NRF2), protects against salt‐induced vascular dysfunction by restoring redox homeostasis in the vasculature. Methods Male Sprague‐Dawley rats and Syrian hamsters were fed a HS (4.0% NaCl) diet containing ~60 mg/kg/day Protandim supplement for 2 weeks and compared to controls fed HS diet alone. Results Protandim supplementation restoredendothelium‐dependent vasodilation in response to acetylcholine (ACh) in middle cerebral arteries (MCA)of HS‐fed rats and hamster cheek pouch arterioles, and increased microvessel density in the cremastermuscle of HS‐fed rats. The restored dilation to ACh in MCA of Protandim‐treated rats was prevented by inhibiting nitric oxide synthase (NOS) with L‐NAME [100 μM] and was absent in MCA from Nrf2 (−/−) knockout rats fed HS diet. Basilar arteries from HS‐fed rats treated with Protandim exhibited significantly lower staining for mitochondrial oxidizing species than untreated animals fed HS diet alone; and Protandim treatment increased MnSOD (SOD2) protein expression in mesenteric arteries of HS‐fed rats. Conclusions These results suggest that dietary activation of NRF2 protects against salt‐induced vascular dysfunction, vascular oxidative stress, and microvascular rarefaction by upregulating antioxidant defenses and reducing mitochondrial ROS levels.
    Type of Medium: Online Resource
    ISSN: 1073-9688 , 1549-8719
    URL: Issue
    URL: Article
    DOI: 10.1111/micc.v26.7
    DOI: 10.1111/micc.12575
    Language: English
    Publisher: Wiley
    Publication Date: 2019
    detail.hit.zdb_id: 2008083-9
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 8
    Online Resource
    Online Resource
    Mutation of Plekha7 attenuates salt-sensitive hypertension in the rat
    Proceedings of the National Academy of Sciences ; 2014
    In:  Proceedings of the National Academy of Sciences Vol. 111, No. 35 ( 2014-09-02), p. 12817-12822
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 111, No. 35 ( 2014-09-02), p. 12817-12822
    Abstract: PLEKHA7 (pleckstrin homology domain containing family A member 7) has been found in multiple studies as a candidate gene for human hypertension, yet functional data supporting this association are lacking. We investigated the contribution of this gene to the pathogenesis of salt-sensitive hypertension by mutating Plekha7 in the Dahl salt-sensitive (SS/JrHsdMcwi) rat using zinc-finger nuclease technology. After four weeks on an 8% NaCl diet, homozygous mutant rats had lower mean arterial (149 ± 9 mmHg vs. 178 ± 7 mmHg; P 〈 0.05) and systolic (180 ± 7 mmHg vs. 213 ± 8 mmHg; P 〈 0.05) blood pressure compared with WT littermates. Albumin and protein excretion rates were also significantly lower in mutant rats, demonstrating a renoprotective effect of the mutation. Total peripheral resistance and perivascular fibrosis in the heart and kidney were significantly reduced in Plekha7 mutant animals, suggesting a potential role of the vasculature in the attenuation of hypertension. Indeed, both flow-mediated dilation and endothelium-dependent vasodilation in response to acetylcholine were improved in isolated mesenteric resistance arteries of Plekha7 mutant rats compared with WT. These vascular improvements were correlated with changes in intracellular calcium handling, resulting in increased nitric oxide bioavailability in mutant vessels. Collectively, these data provide the first functional evidence that Plekha7 may contribute to blood pressure regulation and cardiovascular function through its effects on the vasculature.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.1410745111
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2014
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 9
    Online Resource
    Online Resource
    A role for Nrf2 in the prevention of salt‐induced vascular dysfunction
    Wiley ; 2013
    In:  The FASEB Journal Vol. 27, No. S1 ( 2013-04)
    Details
    In: The FASEB Journal, Wiley, Vol. 27, No. S1 ( 2013-04)
    Type of Medium: Online Resource
    ISSN: 0892-6638 , 1530-6860
    URL: Issue
    URL: Article
    DOI: 10.1096/fsb2.v27.S1
    DOI: 10.1096/fasebj.27.1_supplement.1189.11
    Language: English
    Publisher: Wiley
    Publication Date: 2013
    detail.hit.zdb_id: 1468876-1
    SSG: 12
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 10
    Online Resource
    Online Resource
    Serotonylation of Vascular Proteins Important to Contraction
    Public Library of Science (PLoS) ; 2009
    In:  PLoS ONE Vol. 4, No. 5 ( 2009-5-25), p. e5682-
    Details
    In: PLoS ONE, Public Library of Science (PLoS), Vol. 4, No. 5 ( 2009-5-25), p. e5682-
    Type of Medium: Online Resource
    ISSN: 1932-6203
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.1371/journal.pone.0005682
    DOI: 10.1371/journal.pone.0005682.g001
    DOI: 10.1371/journal.pone.0005682.g002
    DOI: 10.1371/journal.pone.0005682.g003
    DOI: 10.1371/journal.pone.0005682.g004
    DOI: 10.1371/journal.pone.0005682.g005
    DOI: 10.1371/journal.pone.0005682.g006
    DOI: 10.1371/journal.pone.0005682.g007
    Language: English
    Publisher: Public Library of Science (PLoS)
    Publication Date: 2009
    detail.hit.zdb_id: 2267670-3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...