H3P1

Last update 08 May 2025

Basic Info

Synonyms

H3 histone pseudogene 1, H3P1, p02

Introduction-

100 Clinical Results associated with H3P1

100 Translational Medicine associated with H3P1

0 Patents (Medical) associated with H3P1

Literatures (Medical) associated with H3P1

01 Nov 2013·Journal of Investigative DermatologyQ1 · MEDICINE

Mutations in IL36RN in Patients with Generalized Pustular Psoriasis

Q1 · MEDICINE

Letter

Author: Körber, Andreas ; Sticherling, Michael ; Mössner, Rotraut ; Schulz, Peter ; Wilsmann-Theis, Dagmar ; Hüffmeier, Ulrike ; Traupe, Heiko ; Sticht, Heinrich ; Renner, Regina

Generalized pustular psoriasis (GPP) is a rare disorder affecting about 2 per million individuals in Europe (Augey et al., 2006).This severe disease is characterized by repeated flare-ups of pustules and can be accompanied by a potentially life-threatening multisystemic inflammation.Recently, missense mutations in IL36RN have been identified in GPP patients from Tunisia and Europe (Marrakchi et al., 2011; Onoufriadis et al., 2011).In addition, a stop mutation, a novel missense mutation, and mutations affecting splicing of exon 3 have been observed in Japanese patients (Sugiura et al., 2012; Farooq et al., 2013).A group of 19 patients were recruited at five German university hospitals and one specialized dermatol. hospital.In all, 17 patients suffered from typical symptoms of GPP, one patient from psoriasis vulgaris (PsV) with repeated flares of generalized grouped pustules without fever, and another one from PsV with pustules (P19).The three-dimensional structure of human IL36RA was modeled with SwissModel (Guex et al., 2009) using the high-resolution crystal structure of murine IL-1F5 as a template (PDB code: 1MD6; Dunn et al., 2003).Promising variants possibly affecting the structure of IL36RA were generated with SwissModel (Guex et al., 2009), selecting the lowest-energy rotamer for each mutated side chain.We identified homozygous/compound heterozygous variants in seven patients: four patients were homozygous for p.His32Arg, p.Pro76Leu, or p.Ser113Leu, and three further individuals were compound heterozygous for p.Ser113Leu and either p.Arg48Trp, p.Glu94X, or p.Pro76Leu.The stop mutation and the two missense variants p.His32Arg and p.Pro76Leu were, to our knowledge, previously unreported, all affecting highly conserved residues. p.Glu94X disrupted the globular cytokine fold (Figure 1b).His32Arg was not expected to have a significant effect on IL36RA structure/stability, but it possibly has an effect on the interaction with its receptor.Arg48Trp not only affects IL36RA stability, but also affects receptor binding.Four online prediction tools support damaging effects of p.Arg48Trp, p.Pro76Leu, and p.Ser113Leu, whereas the rare variant p.His32Arg was predicted to be neutral (Supplementary Table 1 online).All available unaffected parents of patients (five families) tested as heterozygous mutations carriers.An addnl. coding variant (p.Ser200Asn, according to NM_024110) in CARD14, more recently shown to be relevant for the pathogenesis of PsV and GPP (Jordan et al., 2012a, 2012b), was identified in P02, who developed disease at age 1 yr, but not in P05, whose disease manifested at the age of 17 years (Supplementary Table 2 online). p.Sanger sequencing of CARD14 in another 17 patients revealed three rare variants (rare allele <1%) in two patients (Table 1, Supplementary Table 2 online): p.Located in the CARD domain, it is predicted to be damaging by various anal. tools.We therefore regard it as a contributing factor to P14's GPP.Described to cause autosomal dominant inherited PsV (Jordan et al., 2012b), P08's mutation p.Gly117Ser is probably responsible for long-existing PsV, whereas the addnl. heterozygous IL36RN mutation may have induced his first GPP episode.Our rate of 38.9% IL36RN mutations provides further evidence that GPP is heterogeneous.As such, revealing the mol. basis of GPP in single patients may be clin. important for therapeutic decision making.

01 May 2012·Journal of Neurology

Use of intrathecal clonidine in patients with multiple sclerosis or spastic paraparesis

Letter

Author: Saud A. Sadiq ; Joseph K. Ho

Spasticity and pain are common features of spinal cord disease that may be adequately treated with oral medications in many patients. However, for optimal results it is necessary to use intrathecal baclofen (ITB) or intrathecal morphine (ITM) delivered via a surgically implanted programmable pump in some patients [1–4]. Most patients who need ITB/ITM therapy respond well but in some clinical situations there are problematic issues, including: (1) Occasionally titration of ITB dose is difficult when relief of spasticity is associated with an unacceptable degree of muscle weakness; (2) Rarely patients on continuous long-term ITB therapy develop drug tolerance and cease to respond to escalating doses of ITB [5]; (3) Some patients with pain are intolerant to or rarely, inadequately responsive to intrathecal (IT) narcotics. Clonidine, an a2-adrenergic agonist, inhibits the release of excitatory amino acids from spinal interneurons and the dorsal reticulospinal tract and has anti-spastic and analgesic properties [2]. The hypotensive effects seen with oral clonidine prevent its widespread use in the treatment of spasticity and pain. Intrathecal clonidine (ITC) has been reported to be beneficial for pain relief and in addition, there is a case report on the relief of pain and spasticity in a spinal cord injury patient with the use of combination ITB and ITC [6, 7]. At our center, we have used long-term ITC administered singly or in combination in 21 patients with multiple sclerosis and in isolated cases of various spinal cord disorders (Tables 1, 2). All patients gave a written informed consent prior to the use of ITC. To review our experience, we conducted an IRB-approved retrospective chart analysis of all our patients on continuous ITC therapy. Our review showed that ITC was efficacious in the following circumstances: (1) as a single agent for relief of spasticity in patients who had an unacceptable degree of weakness with the use of ITB (P03, P05; Table 1); (2) as a single agent for relief of spasticity in patients who developed tolerance to ITB after long-term use (P02, P08; Table 1); (3) in patients with spasticity and significant weakness, addition of ITC to ITB enables a reduction in the dose of ITB necessary for spasticity relief, thereby decreasing the degree of weakness and optimizes functionality (P01, P04, P06, P07, P09, P10, P11, P12; Table 1); (4) in combination with ITB in patients with spasticity who also had significant neuropathic pain syndrome and were intolerant to narcotics (P01, P02, P04, P06, P08; Table 2); (5) for relief of pain in patients with intractable pain and suboptimal responses to ITM or ITM/ ITB therapy (Table 2). ITC therapy was empirically initiated at a dose of 30 lg/ day and at this dose clinically beneficial effects were seen in only one patient who required a lesser dose (P05; Table 1). Most patients required doses greater than 100 lg/ day and the maximum dose of ITC used was 750 lg/day (P08; Table 2). Our review shows that ITC is well tolerated over a prolonged period of time with 18 patients receiving ITC for 5 or more years and six patients for at least 10 years. Surprisingly, hypotensive episodes were not seen perhaps because of our low initial dose (30 lg/day) and gradual escalation thereafter. ITC did not appear to be associated with new onset depression or necessitate dose-adjustment J. K. Ho S. A. Sadiq (&) Multiple Sclerosis Research Center of New York, 521 West 57th Street, 4th Floor, New York, NY 10019, USA e-mail: ssadiq@msrcny.org

01 Dec 2007·Journal of the American Chemical SocietyQ1 · CHEMISTRY

Redesign of Protein Domains Using One-Bead-One-Compound Combinatorial Chemistry

Q1 · CHEMISTRY

Article

Author: Granados, Giovanna ; Pastor, Jose J. ; Carulla, Natàlia ; Rabanal, Francesc ; Giralt, Ernest

A novel combinatorial strategy for the redesign of proteins based on the strength and specificity of intra- and interprotein interactions is described. The strategy has been used to redesign the hydrophobic core of the B domain of protein A. Using one-bead-one-compound combinatorial chemistry, 300 analogues of the C-terminal alpha-helix of the B domain, H3x, have been synthesized using a biocompatible resin and the HMFS linker, allowing the screening to occur while the peptides were bound to the resin. The screening was based on the ability of the H3x analogues to interact with the N-terminal helices of the B domain, H1-H2, and retain the native B domain activity, that is binding to IgG. Eight different analogues containing some nonconservative mutations were obtained from the library, the two most frequent of which, H3P1 and H3P2, were studied in detail. CD analysis revealed that the active analogues interact with H1-H2. To validate the redesign strategy the covalent modified domains H1-H2-H3P1 and H1-H2-H3P2 were synthesized and characterized. CD and NMR analysis revealed that they had a unique, stable, and well-defined three-dimensional structure similar to that for the wild-type B domain. This combinatorial strategy allows us to select for redesigned proteins with the desired activity or the desired physicochemical properties provided the right screening test is used. Furthermore, it is rich in potential for the chemical modification of proteins overcoming the drawbacks associated with the total synthesis of large protein domains.

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H3P1

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