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Biomedical subjects

M Olin

Publications and source records attributed to M Olin.

12 recordsLinked to original sources
PubMed2002

Cerebrotendinous xanthomatosis: molecular characterization of two Scandinavian sisters.

Cerebrotendinous xanthomatosis (CTX) is a hereditary disorder, which is inherited as an autosomally recessive disease, causing production of cholesterol and cholestanol xanthomas and mental retardation. The disease is caused by mutations in the gene for sterol 27-hydroxylase (CYP27A1). The only CTX patients diagnosed in Scandinavia are two Norwegian sisters from a consanguineous marriage. Here we have characterized the mutation and its functional consequences for the enzyme. Analysis of genomic DNA from cultured fibroblasts identified a base exchange C > T in position 1441, causing arginine at amino acid position 441 to be replaced by tryptophan. The same mutation was introduced by mutagenesis in the complimentary DNA (cDNA) for CYP27, ligated into the expression vector pcDNA4/HisMax and transfected into HEK293 cells. The mutated enzyme had less than 5% of the enzyme activity compared with the native enzyme. No abnormal catalytic products could be identified in the cell culture medium. Probably the mutation affects the haem binding within the holoenzyme. The mutation has also previously been reported in a Japanese family. This is the second example of a CTX-causing mutation that has been recognized in more than one population.

Adult↗
PubMed1999

Structure and chromosomal assignment of the sterol 12alpha-hydroxylase gene (CYP8B1) in human and mouse: eukaryotic cytochrome P-450 gene devoid of introns.

Sterol 12alpha-hydroxylase (CYP8B1) is a hepatic cytochrome P-450 that controls the ratio of cholic acid over chenodeoxycholic acid in bile and thus controls the solubility of cholesterol. Both the human and the mouse CYP8B1 complementary DNA and gene were cloned and structurally characterized. Surprisingly, the genomic DNA from both species was found to lack introns. The major transcript of the human gene was estimated to be 3950 bp, and the putative promoter region was estimated to be at least 1360 bp. The murine structural gene was found to span approximately 3 kb. By using FISH and radiation hybrid mapping techniques, the human CYP8B1 gene was located to chromosome 3p21.3-p22, whereas FISH mapped the murine counterpart to chromosome 9qF4, a region that is homologous to the third human chromosome. The results from the chromosome mapping and Southern blotting indicated that the gene is present in a single copy. Transcription of the mouse and human CYP8B1 genes was initiated from a position situated 51 and 35 bases, respectively, downstream of a consensus TATA box. A homology of 21% for the promoter regions of mouse and human may indicate differences in transcriptional regulation. Although a potent induction of CYP8B1 mRNA was observed upon starvation of mice, the mechanism behind this effect was not revealed by analysis of the promoter for potential cis-acting elements. In the human promoter, several possible cis-acting regions were identified but none of them could be directly related to bile acid metabolism. After transfection of COS cells with the human coding region, mRNA and enzymatic activity for the 12alpha-hydroxylase were identified. This is the first mammalian cytochrome P-450 gene reported to lack introns. The importance of this structural feature for evolution and gene regulation is discussed.

Amino Acid Sequence↗
PubMed1996

Molecular cloning and expression of rabbit sterol 12alpha-hydroxylase.

Sterol 12alpha-hydroxylase is an important enzyme in bile acid biosynthesis, responsible for the balance between formation of cholic acid and chenodeoxycholic acid. The enzyme has been purified to apparent homogeneity from rabbit liver (Ishida, H., Noshiro, M., Okuda, K., and Coon, M. J. (1992) J. Biol. Chem. 267, 21319-21323), and we here describe the cloning and sequencing of a cDNA coding for this enzyme. After tryptic digestion of purified protein in a polyacrylamide gel, eight different peptides were isolated and sequenced. Using oligonucleotides deduced from the amino acid sequences, clones were isolated from a rabbit liver cDNA library. In addition to several overlapping clones, one full-length clone was obtained that coded for a polypeptide of 500 amino acids, corresponding to a molecular mass of 57 kDa. All of the eight peptides and the reported NH2-terminal amino acid sequence were matched against the sequence. The peptide sequence showed a 39% similarity with human prostacyclin synthase (CYP8) and 31% similarity with the rate-limiting enzyme in over-all synthesis of bile acids, the cholesterol 7alpha-hydroxylase (CYP7) of the rabbit. The similarity with most other sterol cytochrome P-450 hydroxylases was less. Thus, this species of cytochrome P-450 should belong to a group of its own, here denoted CYP12. Transfection of COS cells with the coding part of the cDNA resulted in a significant expression of sterol 12alpha-hydroxylase activity toward 7alpha-hydroxy-4-cholesten-3-one. Northern blotting showed that the enzyme was exclusively expressed in the liver. The major mRNA fraction in rabbit liver had a size of approximately 2.9 kilobases, and those found in rat and human liver were about 2.5 and 4.5 kilobases, respectively. Fasting of rats and mice led to a severalfold increase in both enzyme activity and mRNA levels. In contrast, starvation of rabbits had little or no stimulatory effect on enzyme activity and mRNA levels.

Amino Acid Sequence↗
PubMed1995

A look into the nature and causes of human errors in the intensive care unit.

OBJECTIVES: The purpose of this study was to investigate the nature and causes of human errors in the intensive care unit (ICU), adopting approaches proposed by human factors engineering. The basic assumption was that errors occur and follow a pattern that can be uncovered. DESIGN: Concurrent incident study. SETTING: Medical-surgical ICU of a university hospital. MEASUREMENTS AND MAIN RESULTS: Two types of data were collected: errors reported by physicians and nurses immediately after an error discovery; and activity profiles based on 24-hr records taken by observers with human engineering experience on a sample of patients. During the 4 months of data collection, a total of 554 human errors were reported by the medical staff. Errors were rated for severity and classified according to the body system and type of medical activity involved. There was an average of 178 activities per patient per day and an estimated number of 1.7 errors per patient per day. For the ICU as a whole, a severe or potentially detrimental error occurred on the average twice a day. Physicians and nurses were about equal contributors to the number of errors, although nurses had many more activities per day. CONCLUSIONS: A significant number of dangerous human errors occur in the ICU. Many of these errors could be attributed to problems of communication between the physicians and nurses. Applying human factor engineering concepts to the study of the weak points of a specific ICU may help to reduce the number of errors. Errors should not be considered as an incurable disease, but rather as preventable phenomena.

Ergonomics↗
PubMed1990

Components of complex TM disorders.

Temporomandibular disorders are manifested by pain, dysfunction, or both. When chronicity sets in, initial difficulties become aggravated, and a new set of problems may appear. This paper examines these complexities. Special attention is focused on "whiplash" injuries.

Chronic Disease↗