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P Peterson

Publications and source records attributed to P Peterson.

At least 19 recordsLinked to original sources
PubMed2006

SAP30L interacts with members of the Sin3A corepressor complex and targets Sin3A to the nucleolus.

Histone acetylation plays a key role in the regulation of gene expression. The chromatin structure and accessibility of genes to transcription factors is regulated by enzymes that acetylate and deacetylate histones. The Sin3A corepressor complex recruits histone deacetylases and in many cases represses transcription. Here, we report that SAP30L, a close homolog of Sin3-associated protein 30 (SAP30), interacts with several components of the Sin3A corepressor complex. We show that it binds to the PAH3/HID (Paired Amphipathic Helix 3/Histone deacetylase Interacting Domain) region of mouse Sin3A with residues 120-140 in the C-terminal part of the protein. We provide evidence that SAP30L induces transcriptional repression, possibly via recruitment of Sin3A and histone deacetylases. Finally, we characterize a functional nucleolar localization signal in SAP30L and show that SAP30L and SAP30 are able to target Sin3A to the nucleolus.

Animals↗
PubMed2006

Dose determination of the persistent activity of moxidectin long-acting injectable formulations against various nematode species in cattle.

The effectiveness, safety and production-enhancing benefit (improved weight gains) of moxidectin long-acting injection given subcutaneously in the ear at the rates of 0.75, 1.0 and 1.5mg/kg bw were evaluated in three studies under common protocol. The only adverse reaction to treatment was a mild (<2 tablespoons in volume), and for the most part transient (<28 days for the treatment rate of 1.0mg/kg bw) injection site swelling as noted in a minority of the animals (12.2% of the animals treated at the rate of 1.0mg/kg bw). Regardless of study site, post-treatment interval or dose rate, average daily gains were improved over control cattle by approximately 33%. Reductions in strongyle EPG counts relative to controls were > or = 90% for all dose rates of moxidectin for a post-treatment period of 42 days (Wisconsin), 84 days (Arkansas) and 140 days (Louisiana). In Arkansas and Louisiana, the majority (>80%) of post-treatment strongyle eggs, as determined by coproculture, were Cooperia spp. As determined by sequential necropsies, periods of continuous, post-treatment protection (> or = 90% efficacy in at least two out of three studies) for moxidectin long-acting injection given at the rate of 1.0 mg/kg bw were 90 days (adult Haemonchus spp.), 120 days (Dictyocaulus viviparus and adult Ostertagia and Oesophagostomum) and 150 days (Ostertagia spp. EL4).

Animals↗
PubMed2005

Cooperative activation of transcription by autoimmune regulator AIRE and CBP.

Autoimmune regulator (AIRE) is a transcriptional regulator that is believed to control the expression of tissue-specific genes in the thymus. Mutated AIRE is responsible for onset of the hereditary autoimmune disease APECED. AIRE is able to form nuclear bodies (NBs) and interacts with the ubiquitous transcriptional coactivator CBP. In this paper, we show that CBP and AIRE synergistically activate transcription on different promoter reporters whereas AIRE gene mutation R257X, found in APECED patients, interferes with this coactivation effect. Furthermore, the overexpression of AIRE and CBP collaboratively enhance endogenous IFNbeta mRNA expression. The immunohistochemical studies suggest that CBP, depending on the balance of nuclear proteins, is a component of AIRE NBs. We also show that AIRE NBs are devoid of active chromatin and, therefore, not sites of transcription. In addition, we demonstrate by 3D analyses that AIRE and CBP, when colocalizing, are located spatially differently within AIRE NBs. In conclusion, our data suggest that AIRE activates transcription of the target genes, i.e., autoantigens in collaboration with CBP and that this activation occurs outside of AIRE NBs.

Animals↗
PubMed2005

Infant botulism in the age of botulism immune globulin.

Infant botulism causes acute bulbar dysfunction, weakness, and respiratory failure in infants living in endemic regions of the United States. Until Food and Drug Administration approval of botulism immune globulin (BIG) in October 2003, management of infant botulism had changed little since the 1970s. Currently, IV therapy with BIG is advised to shorten the duration and diminish the potential complications of the disorder. This review describes two decades of experience with infant botulism and provides a contemporary perspective on the role and benefit of BIG.

Botulism↗
PubMed2005

Adalimumab in clinical practice. Outcome in 70 rheumatoid arthritis patients, including comparison of patients with and without previous anti-TNF exposure.

OBJECTIVE: To assess the efficacy and safety of the fully human recombinant monoclonal anti-TNF antibody adalimumab in routine clinical practice, including comparison of patients with and without previous anti-TNF exposure. METHODS: We prospectively studied the outcome of 70 rheumatoid arthritis patients treated with adalimumab in normal clinical practice. The primary outcome measures were Disease Activity Score 28 (DAS28), EULAR (European League Against Rheumatism) response and Health Assessment Questionaire (HAQ). RESULTS: Seventy-seven per cent achieved a EULAR response (26% good, 51% moderate) and 19% were in remission. The mean decrease in DAS28 was 2.1 (6.3-4.2; P<0.001). The mean decrease in HAQ score was 0.34 (2.07-1.73; P<0.001), 66% achieving a clinically significant decrease of greater than 0.22. Twenty-three per cent stopped treatment because of side-effects (7%) or failure to respond (16%). Of the 26 patients who had previously tried 29 biologicals, 65% responded to adalimumab. There was no significant difference in the change in mean DAS (P = 0.69) or HAQ (P = 0.88) between groups with and without previous anti-TNF exposure. Of the 13 patients with previous secondary failure to infliximab, 77% responded to adalimumab. Patients with previous secondary failure had significantly better improvement in DAS (P = 0.023) than patients with previous primary failure. CONCLUSION: Our clinical experience confirms that adalimumab is effective and safe in the treatment of RA. It also shows adalimumab is effective in patients with previous biological failures, particularly patients with secondary failure to infliximab.

Adalimumab↗
PubMed2004

Adult onset Still's disease and collapsing glomerulopathy: successful treatment with intravenous immunoglobulins and mycophenolate mofetil.

In this Grand Round we present a 32-yr-old African man who became severely ill after a 5-month history of weight loss, pyrexia, arthralgia, sweats and rash. He went on to develop pericarditis, pericardial effusion with tamponade, hepatomegaly with abnormal liver function tests, lymphadenopathy, massive proteinuria and required ventilatory, circulatory and renal support. The differential diagnosis was adult onset Still's disease, systemic lupus erythematosus (SLE), infection and lymphoma. Primary infection and lymphoma were excluded and he was treated, with dramatic success, with intravenous immunoglobulins (i.v.IG). Subsequent renal biopsy excluded SLE but confirmed collapsing glomerulopathy. The proteinuria improved dramatically following treatment with mycophenolate mofetil. We discuss some of the difficult diagnostic and management issues raised by this patient and the different uses and mechanisms of action of i.v.IG.

Acute Kidney Injury↗
PubMed2004

A novel tumour necrosis factor receptor mutation in a Finnish family with periodic fever syndrome.

OBJECTIVE: To report a novel mutation of the TNF receptor type 1 gene (TNFRSF1A) in a Finnish patient and her mother, both suffering from periodic fever. METHODS: Soluble TNFRSF1A in serum was measured by enzyme-linked immunoabsorbancy, and induced TNFRSF1A shedding from monocyte cell surfaces was determined using fluorescence-activated cell sorter. Mutation detection was performed using PCR amplification and sequencing of the ten exons of TNFRSF1A. RESULTS: Low levels of soluble TNFRSF1A were detected in both patients between attacks. Sequencing revealed a missense mutation in exon 3 in the second extracellular domain of TNFRSF1A, resulting in a substitution of cysteine with arginine at residue 73 (C73R), confirming the diagnosis of TNF receptor-associated periodic syndrome (TRAPS). We were unable to demonstrate a distinct TNFRSF1A shedding defect. CONCLUSION: In patients of Nordic descent, affected by dominantly inherited recurrent fever, TRAPS is a diagnosis worthy of attention. All TNFRSF1A mutations hitherto described in the Nordic countries have been different.

Adult↗
PubMed2003

Autoimmune regulator: from loss of function to autoimmunity.

The autoimmune regulator (AIRE) is a gene where mutations cause the recessively inherited disorder called autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) or autoimmune polyendocrinopathy syndrome type 1 (APS1). Variable combinations of autoimmune endocrine diseases such as Addison's disease, hypoparathyroidism, and type 1 diabetes characterize APECED. The AIRE protein has several domains indicative of a transcriptional regulator. AIRE contains two PHD (plant homeodomain) type zinc fingers, four nuclear receptor binding LXXLL motifs, a putative DNA-binding domain named SAND and, in addition, a highly conserved N-terminal domain similar to the homogenously staining region domain of the Sp100 protein. At the subcellular level, AIRE is expressed in nuclear dots resembling promyelocytic leukemia nuclear bodies, which are associated with several transcriptionally active proteins. AIRE is primarily expressed in thymic medullary epithelial cells and monocyte-dendritic cells in the thymus but also in a rare subset of cells in the lymph nodes, spleen and fetal liver. The disease, caused by mutations in AIRE, its function as a protein involved in transcription, and its restricted expression in cells important in negative selection, all together suggest that AIRE is a central protein in the maintenance of immune tolerance. In this review of the recent literature we discuss the results of these studies with particular attention on the AIRE expression pattern and its function as a transcriptional regulator, as well as the effects of patient mutations on the molecular characteristics of the protein.

Animals↗
PubMed2001

Subcellular localization of the autoimmune regulator protein. characterization of nuclear targeting and transcriptional activation domain.

The autoimmune regulator (AIRE) gene, defective in the hereditary autoimmune disease APECED, encodes a transcriptional regulator protein. AIRE is expressed in the medullary epithelial cells and monocyte-dendritic cells of the thymus with lower expression in the spleen, fetal liver, and lymph nodes. At the cellular level, AIRE is located in microtubular structures of the cytoskeleton and in discrete nuclear dots resembling ND10 nuclear bodies. We studied the determinants of the targeting of AIRE into these structures. We report here that the N-terminal HSR domain confers localization to the microtubular network whereas the C-terminal region contains a second nuclear localization signal. We also demonstrate that the consensus nuclear localization signal of AIRE is functional and that the HSR domain harbors a nuclear export signal. Accordingly, the nuclear export inhibitor leptomycin B partially inhibits the nuclear export of AIRE. From a functional standpoint, we show that AIRE can activate the interferon beta minimal promoter in a transfection assay and demonstrate that the transcriptional activating function of AIRE is mediated by its two plant homeodomain (PHD) zinc fingers.

Animals↗
PubMed2001

DNA vaccination in mice using HIV-1 nef, rev and tat genes in self-replicating pBN-vector.

The immunogenicity of a self-replicating DNA-vector containing HIV-1 nef gene (pBN-Nef) was characterized using various DNA delivery methods. In addition, gene gun immunisation was used for assessing immunogenicity of two other HIV-1 genes (rev and tat) given in the same vector. The pBN-Nef was the most immunogenic raising both humoral and cell-mediated immune responses in mice; these responses lasted for up to six months. The pBN-Nef vector was immunogenic also when given intramuscularly or intradermally. The pBN-Rev construct did not elicit humoral responses but did elicit proliferative as well as CTL-response against the corresponding protein. The pBN-Tat was a poor immunogen in all respects. The antibodies elicited with various DNA delivery methods belonged to different antibody subclasses; however, two main epitopes in Nef were frequently recognized by all of them.

AIDS Vaccines↗
PubMed2001

APECED mutations in the autoimmune regulator (AIRE) gene.

Autoimmune polyendocrinopathy candidiasis-ectodermal dystrophy (APECED) is a rare recessively inherited disorder caused by mutations in the AIRE (autoimmune regulator) gene. APECED is characterized by variable combinations of endocrine autoimmune diseases such as Addison's disease, hypoparathyroidism, and type 1 diabetes. The AIRE protein contains motifs suggestive of a transcription regulator and can activate transcription of a reporter gene when fused to a heterologous DNA biding domain. In this article, mutation analyses of over 200 APECED patients published by several laboratories are summarized. To date 42 different mutations have been identified. These mutations include nonsense and missense mutations, small insertions and deletions leading into frame shifts, and splice site mutations. Although mutations are spread throughout the coding region of the gene some hotspots emerge, including the more common and recurrent mutations R257X and 967-979del13bp. Some of the identified mutations have been shown to affect subcellular localization or transactivation properties of the protein, thus providing insights into the functional properties of the predicted protein motifs.

Humans↗
PubMed2001

Novel AIRE mutations and P450 cytochrome autoantibodies in Central and Eastern European patients with APECED.

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare recessive disorder that results in several autoimmune diseases due to the mutations in the AIRE (autoimmune regulator) gene. APECED patients develop several autoimmune endocrine disorders and are characterized by the high titer autoantibodies to organ-specific antigens such as the steroidogenic P450 cytochromes. So far, 38 mutations have been identified in the AIRE gene. We report here the genetic and autoantibody analysis of 27 APECED patients of Eastern and Central European origins and one Egyptian patient. From 54 analyzed APECED chromosomes, eight mutations were detected, four of which (T16M, W78R, IVS1_IVS4, 30-53dup23bp) are novel. The most prevalent reason for APECED in these populations was the occurrence of R257X (36 chromosomes) that has been described earlier as a common and recurrent mutation in several other populations. The analysis of humoral immunity to steroidogenic P450 cytochromes by the immunoblotting of E. coli expressed antigens in the 18 APECED patients showed that 67%, 44%, and 61% of the Eastern and Central European APECED patients had autoantibodies to P450c17, P450c21, and P450scc, respectively.

Autoantibodies↗
PubMed2001

Extensive subdural mass.

An unusual case of a 62-year-old man with focal seizures, tinnitus, and progressive left hemiparesis due to an extensive subdural plasma cell granuloma is presented. Five-year clinical and radiologic follow-up demonstrating the chronic yet progressive nature of this granuloma is presented. This is the first report of focal calcification seen in an intracranial plasma cell granuloma. The imaging, neuropathologic, and clinical characteristics of this rare lesion are reviewed.

Brain Diseases↗
PubMed2001

Isolation and initial characterization of the mouse Dnmt3l gene.

We have isolated and sequenced the mouse zinc finger gene, Dnmt3l (DNA cytosine-5-methyltransferase 3-like), on mouse chromosome 10, showing similarity to members of the DNMT3/Dnmt3 family. The Dnmt3l protein contains an ADD zinc finger, which Dnmt3l shares with other Dnmt3 family members and Atrx. RT-PCR analysis showed Dnmt3l expression in testis, thymus, ovary, and heart, as well as in 7-day, 15-day, and 17-day mouse embryos.

Amino Acid Sequence↗