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J Mykkänen

Publications and source records attributed to J Mykkänen.

12 recordsLinked to original sources
PubMed2001

From legacy and client/server systems to components in healthcare information systems in Finland.

A strategy and toolset (FixIT) for migrating a specific type of legacy systems--based on the FileMan DBMS of the U.S. Department of Veterans Affairs--to a two-tier client/server and web browser-based architecture was presented in MEDINFO'98. In the current paper we discuss the further migration to a multitier software component architecture. A literature survey and industry contacts were used to specify an open, component-based target architecture for healthcare information systems to be reached by the year 2005, as well as a phased migration strategy from the present FileMan/FixIT-based systems towards the target. The target architecture is based on large-grained business components and accommodates heterogeneous elements on the intra-component, intra-application, intra-organization and inter-organizational levels. Four logical tiers are identified within a business component. Three migration paths are specified for different cases: the tier-by-tier, piece-by-piece, and web-wrapping paths. It is argued that the architecture, supported by off-the-shelf toolsets, application frameworks and a new software development process, makes it possible to turn legacy systems into a valuable asset, split monolithic applications into reusable components, and ultimately replace the legacy parts at a feasible pace

Database Management Systems↗
PubMed2000

Functional analysis of novel mutations in y(+)LAT-1 amino acid transporter gene causing lysinuric protein intolerance (LPI).

Lysinuric protein intolerance (LPI; MIM 222700) is an autosomal recessive disorder characterized by defective transport of the cationic amino acids lysine, arginine and ornithine at the basolateral membrane of the polar epithelial cells in the intestine and renal tubules, and by hyperammonemia after high-protein meals. LPI is caused by mutations in the SLC7A7 (solute carrier family 7, member 7) gene encoding y(+)LAT-1 (y(+)L amino acid transporter-1), which co-induces together with 4F2 heavy chain (4F2hc) system y(+)L in Xenopus oocytes. All Finnish LPI patients share the same founder mutation 1181-2A-->T (LPI(Fin)) not found in LPI patients elsewhere. Mutation screening of 20 non-Finnish LPI patients revealed 10 novel mutations: four deletions, two missense mutations, two nonsense mutations, a splice site mutation and a tandem duplication. Five LPI mutations (L334R, G54V, 1291delCTTT, 1548delC and LPI(Fin)) were studied functionally. All mutant proteins failed to co-induce amino acid transport activity when expressed with 4F2hc in Xenopus oocytes. Immunostaining experiments revealed that frameshift mutants 1291delCTTT, 1548delC and LPI(Fin)remained intracellular on expression with 4F2hc. In contrast, the missense mutants L334R and G54V reached the oocyte plasma membrane when co-expressed with 4F2hc, demonstrating that they are transport-inactivating mutations. This finding, together with the strong degree of conservation among all members of this family of amino acid transporters, indicates that residues L334 and G54 play a crucial role in the function of the y(+)LAT-1 transporter.

Amino Acid Metabolism, Inborn Errors↗
PubMed2000

Lossless compression of emission tomography images.

An adaptive lossless compression method using predictive coding with the Rice codes is proposed for low resolution three-dimensional biomedical images. The method is evaluated with the brain positron emission tomography (PET) images. The results are considerably better than with static arithmetic coding.

Algorithms↗
PubMed1999

Identification of SLC7A7, encoding y+LAT-1, as the lysinuric protein intolerance gene.

Lysinuric protein intolerance (LPI; OMIM 222700) is a rare, recessive disorder with a worldwide distribution, but with a high prevalence in the Finnish population; symptoms include failure to thrive, growth retardation, muscle hypotonia and hepatosplenomegaly. A defect in the plasma membrane transport of dibasic amino acids has been demonstrated at the baso-lateral membrane of epithelial cells in small intestine and in renal tubules and in plasma membrane of cultured skin fibroblasts from LPI patients. The gene causing LPI has been assigned by linkage analysis to 14q11-13. Here we report mutations in SLC7A7 cDNA (encoding y+L amino acid transporter-1, y+LAT-1), which expresses dibasic amino-acid transport activity and is located in the LPI region, in 31 Finnish LPI patients and 1 Spanish patient. The Finnish patients are homozygous for a founder missense mutation leading to a premature stop codon. The Spanish patient is a compound heterozygote with a missense mutation in one allele and a frameshift mutation in the other. The frameshift mutation generates a premature stop codon, eliminating the last one-third of the protein. The missense mutation abolishes y+LAT-1 amino-acid transport activity when co-expressed with the heavy chain of the cell-surface antigen 4F2 (4F2hc, also known as CD98) in Xenopus laevis oocytes. Our data establish that mutations in SLC7A7 cause LPI.

Adolescent↗
PubMed1999

Characterization of the lysinuric protein intolerance (LPI) region within T-cell receptor alpha/delta gene cluster on chromosome site 14q11.

Lysinuric protein intolerance is a recessively inherited metabolic disease characterized by defective efflux of cationic amino acids at the basolateral membrane of the intestinal and renal tubular epithelium. Linkage analysis and further linkage disequilibrium in Finnish LPI families have earlier assigned LPI gene locus within or in close vicinity of T-cell receptor alpha/delta gene cluster on chromosome site 14q11. In the present work we have characterized the linkage defined LPI region using RH-mapping and fiber-FISH and searched the LPI gene from the reported sequence of the T-cell receptor gene.

Amino Acid Metabolism, Inborn Errors↗
PubMed1999

Feasibility of prenatal diagnosis of lysinuric protein intolerance by linkage analysis: a case report.

Lysinuric protein intolerance (LPI) is a rare autosomal recessive defect of cationic amino acid transport (CAA), relatively common in Finland and Italy. After weaning, LPI patients present poor feeding, vomiting and failure to thrive. A severe pulmonary complication and episodes of metabolic imbalance may lead to death. Prenatal diagnosis has not been available due to lack of either biochemical or molecular markers to be used in the fetal period. The LPI locus has recently been assigned to chromosome 14q12, very close to the T-cell receptor alpha-chain (TCRA) locus. We carried out a prenatal diagnosis for LPI by linkage analysis in one LPI Italian family after CVS. For the haplotype analysis 11 DNA markers from the LPI critical region were used (D14S742, D14S50, D14S283, five TCRA intragenic polymorphic sites, D14S990, MYH7 and D14S80). It was concluded that the haplotype analysis indicated that the fetus was healthy as he had inherited the two wild alleles of the LPI locus. After birth, the clearances of CAA were measured and found to be in the normal range, thus confirming the result of the prenatal diagnosis. The prenatal diagnosis of LPI can now be offered to families affected by LPI.

Adult↗
PubMed1999

Three-dimensional ROIs in brain PET.

A semi-automatic system for determining volumes of interest (VOI) from positron emission tomography (PET) scans of brain is described. The VOIs surface extraction is based on user selectable threshold and three-dimensional target flood-fill. Contrast to anatomical volume detection approaches, volumes are determined from functional PET images and the obtained objects are checked against anatomical images. The developed VOI program was evaluated with brain FDOPA-PET studies where the striatum was the object. The results were comparable to entirely manual method and the target extraction time is reduced to about one third of manual method.

Algorithms↗
PubMed1997

Incidence of aneuploid spermatozoa among infertile men studied by multicolor fluorescence in situ hybridization.

We studied by fluorescence in situ hybridization the frequency of aneuploidy in spermatozoa of 12 infertile men: 8 with normal or nearly normal semen analysis values and 4 with oligo-astheno-teratozoospermia. The control group consisted of 18 normal healthy fertile men. Probes for chromosome 1 and 7 were used and 10,000 spermatozoa per individual were scored. The hybridization efficiency was good (higher than 98%). In the group with nearly normal semen analysis values the frequencies of spermatozoa disomic for chromosome 1 or chromosome 7 were 0.08% and 0.07%, respectively, and not elevated compared to controls (0.10% and 0.06%, respectively). The frequency of diploid spermatozoa was 0.17%, not significantly different from the control group (0.15%) either. In the group of oligoastheno-teratozoospermic men both the frequencies of disomic cells for chromosome 1 (0.22%) and for chromosome 7 (0.13%) and of diploid spermatozoa (0.56%) were significantly higher compared to controls, although this was mainly due to one patient with high frequencies of hyperploid sperm. The results indicate that infertility may be a risk factor for chromosomal aneuploidy in spermatozoa.

Adult↗
PubMed1997

Lysinuric protein intolerance (LPI) gene maps to the long arm of chromosome 14.

Lysinuric protein intolerance (LPI) is an autosomal recessive disease characterized by defective transport of cationic amino acids and by hyperammonemia. Linkage analysis in 20 Finnish LPI families assigned the LPI gene locus to the proximal long arm of chromosome 14. Recombinations placed the locus between framework markers D14S72 and MYH7, a 10-cM interval in which the markers D14S742, D14S50, D14S283, and TCRA showed no recombinations with the phenotype. The phenotype was in highly significant linkage disequilibrium with markers D14S50, D14S283, and TCRA. The strongest allelic association obtained with marker TCRA, resulting in a P(excess) value of .98, suggests that the LPI gene locus lies in close proximity to this marker, probably within a distance of < 100 kb.

Adult↗
PubMed1996

Detection of aneuploidy in human spermatozoa of normal semen donors by fluorescence in situ hybridization.

We have studied human spermatozoa from 24 normal, healthy unexposed men, 18 of whom were semen donors at the Sperm Bank in Turku, using multicolor fluorescence in situ hybridization with two chromosome-specific probes. The possible age-related increase in aneuploidy frequencies was assessed. Ten thousand spermatozoa were scored per individual for the presence of hyperploid, i.e., disomic and diploid, cells. The overall hybridization efficiency was 98.8%. The frequency of spermatozoa with two chromosome 1 signals was 11.5 +/- 5.2/10,000. The frequency of spermatozoa with two chromosome 7 signals was 6.4 +/- 3.9/10,000. Diploidy was present in 15.0 +/- 8.9/10,000 spermatozoa. Interindividual variation was quite large. No statistically significant correlation between age of the donors (range = 20-46 years) and the frequency of hyperploid spermatozoa was observed. The results give background information on the incidence of hyperploid spermatozoa in unexposed men and encourage the use of this novel technique of future studies on genetic effects in men exposed to potentially aneuploidogenic agents.

Adult↗
PubMedDate not supplied

Genetic homogeneity of lysinuric protein intolerance.

Lysinuric protein intolerance (LPI) is an autosomal recessive disorder in which transport of the cationic amino acids lysine, arginine and ornithine is defective at the basolateral membrane of the epithelial cells in the intestine and renal tubules. LPI is unusually common in Finland, but patients have been described on all continents. Linkage analysis in Finnish LPI families recently assigned the LPI gene locus to a 10 cM interval between markers D14S72 and MYH7 on the long arm of chromosome 14. In the present study linkage analysis of LPI families from six different non-Finnish populations strongly suggests genetic homogeneity in LPI. Peak lod scores were obtained at the chromosomal area between D14S72 and MYH7 with the same markers as in the Finnish families. The non-Finnish families showed no linkage disequilibrium except in an Italian family cluster, whereas strong allelic association in the Finnish families implies that LPI in Finland is caused by a founder mutation.

Amino Acid Metabolism, Inborn Errors↗