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Biomedical subjects

Ole Suhr

Publications and source records attributed to Ole Suhr.

5 recordsLinked to original sources
PubMed2005

Chromium(III) ion and thyroxine cooperate to stabilize the transthyretin tetramer and suppress in vitro amyloid fibril formation.

Transthyretin (TTR) amyloid fibril formation, which is triggered by the dissociation of tetrameric TTR, appears to be the causative factor in familial amyloidotic polyneuropathy and senile systemic amyloidosis. Binding of thyroxine (T(4)), a native ligand of TTR, stabilizes the tetramer, but the bioavailability of T(4) for TTR binding is limited due to the preferential binding of T(4) to globulin, the major T(4) carrier in plasma. Here, we show that Cr(3+) increased the T(4)-binding capacity of wild-type (WT) and amyloidogenic V30M-TTR. Moreover, we demonstrate that Cr(3+) and T(4) cooperatively suppressed in vitro fibril formation due to the stabilization of WT-TTR and V30M-TTR.

Amyloid↗
PubMed2005

Heart transplantation in a 68-year-old patient with senile systemic amyloidosis.

Senile systemic amyloidosis (SSA) results from deposition, predominantly in the heart, of amyloid fibrils derived from wild-type transthyretin (T TR) molecules. Cardiac autopsies indicate that SSA progressively increases in subjects 80 years of age and older. However, only a few cases of patients with SSA and cardiac failure have been recognized by cardiac biopsies during life. Here, we report a case of heart transplantation in a 68-year-old male patient with SSA. After cardiopulmonary resuscitation in October 1998, he underwent complete evaluation. Myocardial biopsies revealed the presence of amyloid deposition. Immunohistochemical staining of the amyloid indicated T TR. Genomic DNA analysis of the T TR exons did not result in any identification of a mutation. In 2001, heart transplantation was performed because progressive heart failure occurred. At the 1-year follow-up, no amyloid deposits were found in the donor heart. At the 2-year follow-up, the patient's physical and mental health was excellent. We conclude that heart transplantation can be an effective treatment in progressive heart failure due to SSA.

Aged↗
PubMed2003

Sulfite and base for the treatment of familial amyloidotic polyneuropathy: two additive approaches to stabilize the conformation of human amyloidogenic transthyretin.

Recently, we presented evidence that sulfite protects transthyretin (TTR) from normal human individuals and heterozygotes with amyloidogenic TTR mutations against the decay of tetramers into monomers. In this paper we demonstrate a stabilizing effect of sulfite on TTR tetramers from a familial amyloidotic polyneuropathy (FAP) patient homozygous for the most-common amyloidogenic TTR-V30 M mutation. We compare the conformational stability of partially sulfonated TTR from a heterozygote for normal TTR and amyloidogenic TTR-V30 M with the stability of untreated TTR from a compound heterozygote for amyloidogenic TTR-V30 M and TTR-T119 M known to have only minor or no problems of FAP. Using a combination of polyacrylamide gel electrophoresis (PAGE) and sodium dodecyl sulfate (SDS) gradient PAGE we demonstrate that TTR dimers containing amyloidogenic TTR mutations decay into monomers at pH<7.4. Increasing the pH by some 0.2 units within physiological ranges, i.e., pH 7.0-7.4, and sulfonation of TTR were observed to have additive inhibitory effects on the transition of dimers into monomers. We conclude that mild acidifying episodes in the interstitial volume of tissues at risk for amyloidosis could contribute to the development of FAP. Early and permanent efforts to counteract acidosis by treatment with base could possibly help to delay the onset of the disease. The intake of sulfite could support these efforts.

Acidosis↗
PubMed2002

Peptide YY in gastrointestinal disorders.

The changes in PYY in several gastrointestinal disorders and their possible clinical implications are reviewed. The changes in PYY seem to be an adaptive response to alterations in the patho-physiological condition caused by the disease. This becomes evident in gastrointestinal disorders such as diabetes gastroenteropathy, inflammatory bowel diseases, celiac disease, systemic sclerosis and post-intestinal resection state. On the other hand, changes in PYY in chronic idiopathic slow transit constipation appear to be primary and could be one of the etiologic factors of the disease. PYY does not seem to be involved in colorectal carcinoma. Although gastrointestinal dysmotility in neuro-muscular diseases is evident, PYY is not affected. The changes in PYY in gastrointestinal disorders could be beneficial in clinical practice. Thus, in cases where an increase or decrease in PYY is desirable, a diet that increases or decreases PYY synthesis and release can be followed, or a receptor agonist or antagonist can be utilized.

Anorexia↗