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Hultman, Per
Alternative names
Publications (10 of 72) Show all publications
Cauvi, D., Hultman, P. & Pollard, K. M. (2015). Autoimmune models. In: Reference module in biomedical sciences: (pp. 413-438). Elsevier
Open this publication in new window or tab >>Autoimmune models
2015 (English)In: Reference module in biomedical sciences, Elsevier, 2015, p. 413-438Chapter in book (Refereed)
Abstract [en]

Models of autoimmunity fall into four categories: (a) those induced by immunization with self-antigen, (b) those induced by exogenous agents, (c) those which arise spontaneously, and (d) those which are produced by genetic manipulation. The autoimmunity exhibited by these models covers a spectrum of diseases which fall into the two broad categories, organ-specific and systemic autoimmunity. Animal models of autoimmune diseases have played an essential role in the discovery of many of mechanisms that result in the breaking of self-tolerance. This chapter describes a number of experimental animal models of autoimmunity and the underlying mechanisms that lead to disease.

Place, publisher, year, edition, pages
Elsevier, 2015
Keywords
Animal model; Autoimmunity; Chemical-induced; Diabetes; Encephalomyelitis; Gastritis; Immune tolerance; Lupus; Mercury; Metal; Nephritis; Silica; Thyroiditis
National Category
Immunology in the medical area
Identifiers
urn:nbn:se:liu:diva-116714 (URN)9780128012383 (ISBN)
Available from: 2015-04-01 Created: 2015-04-01 Last updated: 2018-01-11Bibliographically approved
Cauvi, D. M., Gabriel, R., Kono, D. H., Hultman, P. & Pollard, K. M. (2014). A tandem repeat in decay accelerating factor 1 is associated with severity of murine mercury-induced autoimmunity. Autoimmune Diseases, 2014(260613)
Open this publication in new window or tab >>A tandem repeat in decay accelerating factor 1 is associated with severity of murine mercury-induced autoimmunity
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2014 (English)In: Autoimmune Diseases, ISSN 2090-0422, E-ISSN 2090-0430, Vol. 2014, no 260613Article in journal (Refereed) Published
Abstract [en]

Decay accelerating factor (DAF), a complement-regulatory protein, protects cells from bystander complement-mediated lysis and negatively regulates T cells. Reduced expression of DAF occurs in several systemic autoimmune diseases including systemic lupus erythematosus, and DAF deficiency exacerbates disease in several autoimmune models, including murine mercury-induced autoimmunity (mHgIA). Daf1, located within Hmr1, a chromosome 1 locus associated in DBA/2 mice with resistance to mHgIA, could be a candidate. Here we show that reduced Daf1 transcription in lupus-prone mice was not associated with a reduction in the Daf1 transcription factor SP1. Studies of NZB mice congenic for the mHgIA-resistant DBA/2 Hmr1 locus suggested that Daf1 expression was controlled by the host genome and not the Hmr1 locus. A unique pentanucleotide repeat variant in the second intron of Daf1 in DBA/2 mice was identified and shown in F2 intercrosses to be associated with less severe disease; however, analysis of Hmr1 congenics indicated that this most likely reflected the presence of autoimmunity-predisposing genetic variants within the Hmr1 locus or that Daf1 expression is mediated by the tandem repeat in epistasis with other genetic variants present in autoimmune-prone mice. These studies argue that the effect of DAF on autoimmunity is complex and may require multiple genetic elements.

Place, publisher, year, edition, pages
Hindawi Publishing Corporation, 2014
National Category
Medical Genetics
Identifiers
urn:nbn:se:liu:diva-116712 (URN)10.1155/2014/260613 (DOI)24818014 (PubMedID)2-s2.0-84900019378 (Scopus ID)
Available from: 2015-04-01 Created: 2015-04-01 Last updated: 2018-01-16
Hultman, P. & Pollard, K. M. (2014). Immunotoxicology of metals (4ed.). In: Gunnar Nordberg, Bruce Fowler, Monica Nordberg (Ed.), Handbook on the toxicology of metals,: (pp. 379-298). Academic Press
Open this publication in new window or tab >>Immunotoxicology of metals
2014 (English)In: Handbook on the toxicology of metals, / [ed] Gunnar Nordberg, Bruce Fowler, Monica Nordberg, Academic Press, 2014, 4, p. 379-298Chapter in book (Refereed)
Place, publisher, year, edition, pages
Academic Press, 2014 Edition: 4
Series
Handbook on the Toxicology of Metals
Keywords
Metaller, Toxikologi
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-116710 (URN)978-04-4459-453-2 (vol 1) (ISBN)978-01-2398-293-3 (vol. 2) (ISBN)
Available from: 2015-04-01 Created: 2015-04-01 Last updated: 2015-04-16Bibliographically approved
Olsson, H., Söderkvist, P., Hultman, P., Rosell, J. & Jahnson, S. (2013). MDM2 SNP309 promoter polymorphism and p53 mutations in urinary bladder carcinoma stage T1. BMC Urology, 13(5)
Open this publication in new window or tab >>MDM2 SNP309 promoter polymorphism and p53 mutations in urinary bladder carcinoma stage T1
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2013 (English)In: BMC Urology, ISSN 1471-2490, E-ISSN 1471-2490, Vol. 13, no 5Article in journal (Refereed) Published
Abstract [en]

Background: Urinary bladder carcinoma stage T1 is an unpredictable disease that in some cases has a good prognosis with only local or no recurrence, but in others can appear as a more aggressive tumor with progression to more advanced stages. The aim here was to investigate stage T1 tumors regarding MDM2 promoter SNP309 polymorphism, mutations in the p53 gene, and expression of p53 and p16 measured by immunohistochemistry, and subsequently relate these changes to tumor recurrence and progression. We examined a cohort of patients with primary stage T1 urothelial carcinoma of the bladder and their tumors.

Methods: After re-evaluation of the original slides and exclusions, the study population comprised 141 patients, all with primary stage T1 urothelial carcinoma of the bladder. The hospital records were screened for clinical parameters and information concerning presence of histologically proven recurrence and progression. The paraffin-embedded tumor material was evaluated by immunohistochemistry. Any mutations found in the p53 gene were studied by single-strand conformation analysis and Sanger sequencing. The MDM2 SNP309 polymorphism was investigated by pyrosequencing. Multivariate analyses concerning association with prognosis were performed, and Kaplan-Meier analysis was conducted for a combination of changes and time to progression.

Results: Of the 141 patients, 82 had at least one MDM2 SNP309 G allele, and 53 had a mutation in the p53 gene, but neither of those anomalies was associated with a worse prognosis. A mutation in the p53 gene was associated with immunohistochemically visualized p53 protein expression at a cut-off value of 50%. In the group with p53 mutation Kaplan-Meier analysis showed higher rate of progression and shorter time to progression in patients with immunohistochemically abnormal p16 expression compared to them with normal p16 expression (p = 0.038).

Conclusions: MDM2 SNP309 promoter polymorphism and mutations in p53 were not associated with worse prognosis in this cohort of patients with primary stage T1 urinary bladder carcinoma. However, patients with abnormal p16 expression and a mutated p53 gene had a higher rate of and a shorter time to progression, and p53 gene mutation was associated with an abnormal immunohistochemistry for p53 at a cut-off of 50%.

Place, publisher, year, edition, pages
BioMed Central, 2013
Keywords
Urinary bladder cancer, immunohistochemistry, prognostic factors, cell cycle regulators
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-85016 (URN)10.1186/1471-2490-13-5 (DOI)000314924600001 ()
Available from: 2013-04-02 Created: 2012-10-30 Last updated: 2017-12-07Bibliographically approved
Hadimeri, U., Hultman, P., Larsson, R., Melander, S., Mölne, J. & Hadimeri, H. (2013). Membranoproliferative Glomerulonephritis and Inflammatory Pseudotumour of the Spleen. Case Reports in Oncology, 6(1), 84-89
Open this publication in new window or tab >>Membranoproliferative Glomerulonephritis and Inflammatory Pseudotumour of the Spleen
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2013 (English)In: Case Reports in Oncology, ISSN 1662-6575, E-ISSN 1662-6575, Vol. 6, no 1, p. 84-89Article in journal (Refereed) Published
Abstract [en]

Inflammatory pseudotumour is a rare condition that can affect various organs. The clinical and histologic appearance of the pseudotumour may mimic haematological, lymphoproliferative, paraneoplastic or malignant processes. A previously healthy 39-year-old man presented with nephrotic syndrome. He had a history of headaches, nausea and swollen ankles. Computed tomography of the abdomen revealed a 6-cm mass in the spleen. Following a renal biopsy, a diagnosis of membranoproliferative glomerulonephritis (MPGN) type I was made. Splenectomy was performed and the examination revealed a mixed population of lymphocytes with predominantly T-cells, B-cells and lymphoplasmacytoid cells. Immunostaining confirmed that the small cells were mostly T-cells positive for all T-cell markers including CD2, CD3, CD4, CD5, CD7 and CD8. A diagnosis of inflammatory pseudotumour was established. The removal of the spleen was followed by remission of glomerulonephritis, but it was complicated by a subphrenic abscess and pneumonia. This association between an inflammatory pseudotumour of the spleen and MPGN has not been previously described. Abnormal immune response due to the inflammation leading to secondary glomerulonephritis might be the main pathogenic mechanism.

Place, publisher, year, edition, pages
S. Karger, 2013
Keywords
Inflammatory pseudotumour, Spleen, Membranoproliferative glomerulonephritis
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-96970 (URN)10.1159/000347229 (DOI)
Available from: 2013-09-02 Created: 2013-09-02 Last updated: 2017-12-06
Myhrinder, A. L., Hellqvist, E., Jansson, M., Nilsson, K., Hultman, P., Jonasson, J., . . . Rosén, A. (2013). Molecular characterization of neoplastic and normal "sister" lymphoblastoid B-cell lines from chronic lymphocytic leukemia. Leukemia and Lymphoma, 54(8), 1769-1779
Open this publication in new window or tab >>Molecular characterization of neoplastic and normal "sister" lymphoblastoid B-cell lines from chronic lymphocytic leukemia
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2013 (English)In: Leukemia and Lymphoma, ISSN 1042-8194, E-ISSN 1029-2403, Vol. 54, no 8, p. 1769-1779Article in journal (Refereed) Published
Abstract [en]

Chronic lymphocytic leukemia (CLL) B-cells resemble self-renewing CD5 + B-cells carrying auto/xeno-antigen-reactive B-cell receptors (BCRs) and multiple innate pattern-recognition receptors, such as Toll-like receptors and scavenger receptors. Integration of signals from BCRs with multiple surface membrane receptors determines whether the cells will be proliferating, anergic or apoptotic. To better understand the role of antigen in leukemogenesis, CLL cell lines producing monoclonal antibodies (mAbs) will facilitate structural analysis of antigens and supply DNA for genetic studies. We present here a comprehensive genotypic and phenotypic characterization of available CLL and normal B-cell-derived lymphoblastoid cell lines (LCLs) from the same individuals (n = 17). Authenticity and verification studies of CLL-patient origin were done by IGHV sequencing, fluorescence in situ hybridization (FISH) and DNA/short tandem repeat (STR) fingerprinting. Innate B-cell features, i.e. natural Ab production and CD5 receptors, were present in most CLL cell lines, but in none of the normal LCLs. This panel of immortalized CLL-derived cell lines is a valuable reference representing a renewable source of authentic Abs and DNA.

Place, publisher, year, edition, pages
Informa Healthcare, 2013
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-16340 (URN)10.3109/10428194.2013.764418 (DOI)000321763800032 ()
Available from: 2009-01-16 Created: 2009-01-16 Last updated: 2017-12-14Bibliographically approved
Olsson, H., Hultman, P., Rosell, J. & Jahnson, S. (2013). Population-based study on prognostic factors for recurrence and progression in primary stage T1 bladder tumours. Scandinavian Journal of Urology and Nephrology, 47(3), 188-195
Open this publication in new window or tab >>Population-based study on prognostic factors for recurrence and progression in primary stage T1 bladder tumours
2013 (English)In: Scandinavian Journal of Urology and Nephrology, ISSN 0036-5599, E-ISSN 1651-2065, Vol. 47, no 3, p. 188-195Article in journal (Refereed) Published
Abstract [en]

Objective. Stage T1 urothelial carcinoma of the bladder (UCB) exhibits heterogeneous clinical behaviour, and the treatment is controversial. The aim of this study was to evaluate prognostic factors for UCB in a defined, population-based cohort comprising patients with a first time diagnosis of primary stage T1 UCB.

Material and methods. The study population initially consisted of 285 patients with primary stage T1 UCB reported to the regional Bladder Cancer Registry in the Southeast Healthcare Region of Sweden from 1992 to 2001. The histological specimens were re-evaluated concerning stage, substaging of T1, World Health Organization (WHO) grade, lymphovascular invasion (LVI), tumour volume and total resected volume. Hospital records provided data on tumour size and multiplicity, occurrence of possible relapse and/or progression, death from UCB and whether treatment was given.

Results. After re-evaluation, the study population comprised 211 patients. The median follow-up time was 60 months. LVI was a prognostic factor for UCB progression and recurrence. Tumour size larger than 30 mm and multiplicity increased the risk of recurrence. T1 substaging, tumour volume and total resected volume were not associated with recurrence or tumour progression.

Conclusions. LVI is significantly correlated with progression and recurrence in patients with primary stage T1 UCB. Therefore, the presence of LVI should be evaluated in every new case of T1 UCB.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-85012 (URN)10.3109/00365599.2012.719539 (DOI)000321415400004 ()
Available from: 2012-10-30 Created: 2012-10-30 Last updated: 2017-12-07Bibliographically approved
Pollard, M. K., Hultman, P., Toomey, C. B., Cauvi, D. M., Hoffman, H. M., Hamel, J. C. & Kono, D. H. (2012). Definition of IFN-gamma-related pathways critical for chemically-induced systemic autoimmunity. Journal of Autoimmunity, 39(4), 323-331
Open this publication in new window or tab >>Definition of IFN-gamma-related pathways critical for chemically-induced systemic autoimmunity
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2012 (English)In: Journal of Autoimmunity, ISSN 0896-8411, E-ISSN 1095-9157, Vol. 39, no 4, p. 323-331Article in journal (Refereed) Published
Abstract [en]

IFN-gamma is essential for idiopathic and murine mercury-induced systemic autoimmunity (mHgIA), and heterozygous IFN-gamma(+/-) mice also exhibit reduced disease. This suggests that blocking specific IFN-gamma-related pathways that may only partially inhibit IFN-gamma production or function will also suppress autoimmunity. To test this hypothesis, mice deficient in genes regulating IFN-gamma expression (Casp1, Nlrp3, Il12a, Il12b, Stat4) or function (Ifngr1, Irf1) were examined for mHgIA susceptibility. Absence of either Ifngr1 or Irf1 resulted in a striking reduction of disease, while deficiency of genes promoting IFN-gamma expression had modest to no effect. Furthermore, both Irf1- and Ifng-deficiency only modestly reduced the expansion of CD44(hi) and CD44(hi)CD55(lo) CD4(+) T cells, indicating that they are not absolutely required for T cell activation. Thus, there is substantial redundancy in genes that regulate IFN-gamma expression in contrast to those that mediate later signaling events. These findings have implications for the therapeutic targeting of IFN-gamma pathways in systemic autoimmunity.

Place, publisher, year, edition, pages
Elsevier, 2012
Keywords
Interferon, Animal model, Mercury
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-88671 (URN)10.1016/j.jaut.2012.04.003 (DOI)000313465800009 ()
Note

Funding Agencies|NIH|ES007511ES014847AI052430AR053731|Swedish Research Council Branch of Medicine|09453|

Available from: 2013-02-14 Created: 2013-02-14 Last updated: 2017-12-06
Olsson, H., Fyhr, I.-M., Hultman, P. & Jahnson, S. (2012). HER2 status in primary stage T1 urothelial cell carcinoma of the urinary bladder. Scandinavian Journal of Urology and Nephrology, 46(2), 102-107
Open this publication in new window or tab >>HER2 status in primary stage T1 urothelial cell carcinoma of the urinary bladder
2012 (English)In: Scandinavian Journal of Urology and Nephrology, ISSN 0036-5599, E-ISSN 1651-2065, Vol. 46, no 2, p. 102-107Article in journal (Refereed) Published
Abstract [en]

Objective. The HER2 receptor is involved in pathways essential for cell proliferation, and is an important predictive and prognostic factor in breast cancer. HER2 probably plays a critical role in many types of cancer, including urothelial carcinoma of the bladder (UCB). Stage T1 UCB exhibits heterogeneous clinical behaviour, and the frequency of HER2 expression in such disease has not been thoroughly examined. The aim of this study was to use an immunohistochemical technique to evaluate the frequency of HER2 expression in a defined population-based cohort of patients registered as having primary stage T1 UCB. Material and methods. The initial study population comprised 285 patients registered as having primary stage T1 UCB. The original histological specimens were re-evaluated with regard to T stage and World Health Organization grade. Hospital records provided information on tumour size, multiplicity, possible presence of histologically proven recurrence and progression. The patients were followed for at least 5 years or until death. In tumours still considered stage T1 after re-evaluation, HER2 was investigated by immunohistochemistry of paraffin-embedded material and scored according to the guidelines used in breast cancer. Results. After histopathological re-evaluation, 201 patients were still T1 UCB and could be investigated regarding HER2 expression. HER2 overexpression was observed in 25 of those patients (12.4%). HER2 status was not significantly associated with recurrence or progression. Conclusions. HER2 was overexpressed in 12.4% of the present cohort of patients with primary stage T1 UCB. There was no significant association between tumour HER2 status and prognosis.

Place, publisher, year, edition, pages
Informa Healthcare, 2012
Keywords
HER2 overexpression, stage T1, urinary bladder carcinoma
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-76526 (URN)10.3109/00365599.2011.637955 (DOI)000301539200005 ()
Available from: 2012-04-12 Created: 2012-04-11 Last updated: 2017-12-07
Olsson, H., Hultman, P., Monsef, N., Rosell, J. & Johanson, S. (2012). Immunohistochemical Evaluation of Cell Cycle Regulators: Impact on Predicting Prognosis in Stage T1 Urinary Bladder Cancer. ISRN Urology, 2012, Article ID 379081.
Open this publication in new window or tab >>Immunohistochemical Evaluation of Cell Cycle Regulators: Impact on Predicting Prognosis in Stage T1 Urinary Bladder Cancer
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2012 (English)In: ISRN Urology, ISSN 2090-5807, E-ISSN 2090-5815, Vol. 2012, article id 379081Article in journal (Other academic) Published
Abstract [en]

Background and Objective. The cell cycle is regulated by proteins at different checkpoints, and dysregulation of this cycle plays a role in carcinogenesis. Matrix metalloproteinases (MMPs) are enzymes that degrade collagen and promote tumour infiltration. The aim of this study was to evaluate the expression of various cell cycle regulators and MMPs, and to correlate such expression with progression and recurrence in patients with stage T1 urothelial carcinoma of the bladder (UCB).

Patients and Methods. This population-based cohort study comprised 201 well-characterized patients with primary stage T1 urothelial carcinoma of the bladder. Immunohistochemistry was performed on formalin-fixed material to quantify expression of cell cycle regulators and two MMPs.

Results. Normal expression of p53 and abnormal expression of MMP9 were associated with greater risk of tumour recurrence. Also, normal p16 expression was related to a lower risk of tumour progression. MMP2, p21, cyclin D1, and pRb showed no significant results that could estimate progression or recurrence.

Conclusions. Normal p16 expression is associated with a lower risk of tumour progression, but immunohistochemistry on cell cycle regulators and MMPs has little value in predicting the prognosis in stage T1 UCB.

Place, publisher, year, edition, pages
Hindawi Publishing Corporation, 2012
Keywords
Urinary bladder cancer, immunohistochemistry, prognostic factors, cell cycle regulators
National Category
Clinical Laboratory Medicine
Identifiers
urn:nbn:se:liu:diva-85013 (URN)10.5402/2012/379081 (DOI)
Note

On the day of the defence day the status of this article was:

Manuscript

Available from: 2012-10-30 Created: 2012-10-30 Last updated: 2017-12-07Bibliographically approved
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