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R Kemppainen

Publications and source records attributed to R Kemppainen.

8 recordsLinked to original sources
PubMed1997

A homozygous nonsense mutation and a combination of two mutations of the Wilson disease gene in patients with different lysyl oxidase activities in cultured fibroblasts.

Wilson disease is a rare autosomal recessive disease of copper metabolism. The gene for Wilson disease was characterized recently and has been predicted to encode a copper-transporting ATPase highly homologous to the protein encoded by the gene of Menkes disease. In this study, the genetic mutations of two Finnish patients with Wilson disease were investigated. One patient was homozygous for a novel nonsense mutation in exon 4, while the other was a compound heterozygote. Lysyl oxidase (EC 1.4.3.13) is an extracellular copper enzyme with deficient activity in Menkes disease. The levels of lysyl oxidase activity in cultured skin fibroblasts from these Wilson disease patients were also measured.

Adult↗
PubMed1996

Expression of mRNAs for lysyl oxidase and type III procollagen in cultured fibroblasts from patients with the Menkes and occipital horn syndromes as determined by quantitative polymerase chain reaction.

The Menkes syndrome and the occipital horn syndrome are two X-linked recessively inherited disorders characterized by abnormalities in copper metabolism. These abnormalities are associated with a reduction in the activity of lysyl oxidase (EC 1.4.3.13), an extracellular copper enzyme that initiates the crosslinking of collagens and elastin. We report here that the amount of lysyl oxidase mRNA, as studied by Northern blotting, and the number of lysyl oxidase mRNA molecules per picogram of RNA, as determined by a quantitative PCR method, were decreased in three cultured skin fibroblast lines from patients with the Menkes syndrome and two from patients with the occipital horn syndrome compared with four control cell lines. The decreased lysyl oxidase activity found in these disorders thus appears to be a least in part due to a pretranslational mechanism. No decrease was found in the number of the beta-actin mRNA molecules in the Menkes cell lines, but rather a slight increase, whereas a decrease was found in these molecules in the occipital horn cell lines. An additional abnormality found in the Menkes cell lines was a significant increase in the number of mRNA molecules for type III procollagen in two of the three cell lines investigated. The present and previous data indicate that the Menkes syndrome may involve several abnormalities in the expression of genes for connective tissue proteins.

Base Sequence↗
PubMed1995

Quantitative polymerase chain reaction of lysyl oxidase mRNA in malignantly transformed human cell lines demonstrates that their low lysyl oxidase activity is due to low quantities of its mRNA and low levels of transcription of the respective gene.

Lysyl oxidase (EC 1.4.3.13), an extracellular copper amino oxidase, initiates the cross-linking of collagens and elastin by catalyzing oxidative deamination of the epsilon-amino group in certain lysine and hydroxylysine residues. We developed here a polymerase chain reaction (PCR) method for the quantification of lysyl oxidase mRNA in which a synthetic RNA is used as an internal standard for coamplification with the targeted mRNA. The amount of lysyl oxidase mRNA when studied by Northern blot analysis and the number of lysyl oxidase mRNA molecules when determined by the quantitative PCR method were found to be markedly low in various malignantly transformed cell lines relative to control cell lines, quantitative PCR indicating values of about 2-10% of those in the controls. No difference was found in the number of beta-actin mRNA molecules between the transformed cells and the controls. Nuclear runoff experiments indicated that most if not all of the decrease in the number of lysyl oxidase mRNA molecules can be explained by diminished transcription of the respective gene.

Adult↗
PubMed1993

Structure of the human lysyl oxidase gene.

Lysyl oxidase (EC 1.4.3.13), an extracellular copper enzyme, initiates the crosslinking of collagens and elastin by catalyzing oxidative deamination of the epsilon-amino group in certain lysine and hydroxylysine residues. We report here that the human lysyl oxidase gene is about 15 kb in size and consists of seven exons. Transcription is initiated at one major site and four minor sites, and the first exon consists of 273 bp of untranslated sequences (calculated to the major site) and 631 bp of translated sequences, which accounts for about half of all the translated sequences of the gene. The seventh exon, on the other hand, codes for only the last codon of amino acid 416 and for amino acid 417, which are followed by the translation termination codon and the 3' untranslated sequences. Exons 2-6 vary in size from 96 to 157 bp, and the introns from 331 bp to about 3.5 kb. The 5' flanking region contains a TATA-like sequence at -30 relative to the major transcription initiation site and a CCAAT motif at -109. The 5' flanking region and the downstream sequences present in the first exon and first intron contain altogether five possible binding sequences for Sp1, six for AP-2, one for AP-1, three for PEA3, three for MEP-1, and three CCCTCCC motifs, all of which may be involved in the regulation of the expression of the gene.

Amino Acid Sequence↗
PubMed1984

Asbestosis, the nervous system and cancer.

Asbestosis patients have a high cumulative risk of cancer: four of ten asbestosis patients develop cancer. Paraneoplastic involvement of the nervous system, peripheral neuropathy in particular, is often encountered in cancer patients, even at very early stages of the disease. In order to estimate the occurrence of paraneoplastic neuropathy among asbestosis patients, we formed a small cohort (115 asbestosis patients, mean age 56 years, mean duration of exposure to asbestos 21 years) in 1979. Neurological examination revealed slight peripheral neuropathy in 44 (39%) of the patients, 24 (22%) of whom also had central nervous system signs (disturbances in gait and posture, memory and fine movements). The prevalence of peripheral neuropathy among asbestosis patients was higher than among various referent patients (fibrosing alveolitis, diagnosed solvent poisoning and gynaecological carcinoma). No significant differences were found between the patients with and without peripheral neuropathy regarding the following parameters: pulmonary function tests, tumour markers (CEA, ferritin, beta-2-microglobulin), antinuclear antibodies, C3, C4 and circulating immune complexes. Nevertheless, at group level, the asbestosis patients had increased levels of the three tumour markers. Estimates based on the data accumulated so far (10 cancer patients) show that within three years we shall probably have a sufficient number of cancer cases to draw some conclusions about the value of neuropathy in the early diagnosis of occupational cancer.

Adult↗
PubMed1982

Drinking habits and peripheral alcoholic neuropathy.

Drinking habits of 156 consecutive polyneuropathic and 106 consecutive pressure palsy patients were evaluated in retrospect. Respectively, 46 patients (30%) had alcohol polyneuropathy and 32 (30%) got pressure neuropathy while being drunk and these patients were analyzed in more detail. Most of the patients with alcoholic neuropathies were men, those with polyneuropathy being older than those having pressure palsies. Pressure neuropathy coincided with alcoholic polyneuropathy in 13 patients (28%). Other medical complication of heavy alcohol drinking (i.e. liver diseases, seizures and cerebellar signs) were seen in 54% of the patients with polyneuropathy and in 6% of the patients with pressure palsies. Heavy drinking prolonged the disability due to pressure palsy. The present study confirms the significant role of alcohol abuse in etiology of peripheral neuropathies. Heavy drinking seems to worsen the prognosis of these neuropathies.

Adult↗