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J Partanen

Publications and source records attributed to J Partanen.

At least 37 records · Page 2Linked to original sources
PubMed1998

Assignment of the tibial muscular dystrophy locus to chromosome 2q31.

Tibial muscular dystrophy (TMD) is a rare autosomal dominant distal myopathy with late adult onset. The phenotype is relatively mild: muscle weakness manifests in the patient's early 40s and remains confined to the tibial anterior muscles. Histopathological changes in muscle are compatible with muscular dystrophy, with the exception that rimmed vacuoles are a rather common finding. We performed a genomewide scan, with 279 highly polymorphic Cooperative Human Linkage Center microsatellite markers, on 11 affected individuals of one Finnish TMD family. The only evidence for linkage emerged from markers in a 43-cM region on chromosome 2q. In further linkage analyses, which included three other Finnish TMD families and which used a denser set of markers, a maximum two-point LOD score of 10.14 (recombination fraction of .05) was obtained with marker D2S364. Multipoint likelihood calculations, combined with the haplotype and recombination analyses, restricted the TMD locus to an approximately 1-cM critical chromosomal region without any evidence of heterogeneity. Since all the affecteds share one core haplotype, the dominance of one ancestor mutation is obvious in the Finnish TMD families. The disease locus that was found represents a novel muscular dystrophy locus, providing evidence for the involvement of one additional gene in the distal myopathy group of muscle disorders.

Adult↗
PubMed1998

TNF microsatellite alleles a2 and b3 are not primarily associated with celiac disease in the Finnish population.

Recently, an independent association between tumor necrosis factor (TNF) gene polymorphism and celiac disease was observed in the Irish population. We tested this association in Finnish patients with celiac disease. The TNF microsatellite alleles a2 and b3 were strongly associated (Pcorr<0.0001 for both) with celiac disease when the patients were compared to the random population. However, when the comparison was made with the DQ2-matched controls, no association could be found. We therefore conclude that in Finland the TNFa2 and b3 alleles are associated with DQ2-positive haplotypes rather than celiac disease.

Alleles↗
PubMed1998

Genetic polymorphism in human platelet glycoprotein GP Ib/IX/V complex is enriched in GP V (CD42d).

Platelet glycoproteins Ib beta (CD42c), IX (CD42a), and V (CD42d), together with GP Ib alpha (CD42b), form a receptor whose interaction with the von Willebrand factor is essential in the initial stages of haemostasis. Genetic variation in these proteins can cause alloimmunization leading to neonatal alloimmune thrombocytopenia and platelet transfusion refractoriness. Defective mutations cause a rare bleeding disorder, Bernard-Soulier syndrome. Only two antigenic polymorphisms have thus far been established in these proteins: the HPA-2 in GP Ib alpha and the rare Iy variant in GP Ib beta. Recently, we reported that only a limited degree of polymorphism can be found in the GP Ib alpha gene; the level of variation in the other components is not known. We therefore systematically screened polymorphism in the GP Ib beta, GP IX, and GP V genes in 50 unrelated Finnish blood donors. Nine polymorphic sites were found in the GP V gene, of which four changed the amino acid code and five were silent. The gene frequencies for substitutions Asp114Tyr, Met273Ile, Gly341Arg, and Leu397Arg were 1%, 1%, 2%, and 1% respectively. The five silent polymorphisms also had low frequencies, 1-4%. No polymorphism was found in the GP Ib beta gene and only one mutation was found in the 3' untranslated region of the GP IX gene. Our results indicate that genetic variation in the GP Ib/IX/V complex is mostly tolerated in the GP V protein--whose function in the complex is not clear whereas the other components have only very limited genetic polymorphism.

Blood Donors↗
PubMed1998

Genetic susceptibility to gluten sensitive enteropathy in Irish setter dogs is not linked to the major histocompatibility complex.

Gluten sensitive enteropathy (GSE) in Irish setter dogs has been proposed as an animal model for human celiac disease (CD), in which the major histocompatibility complex (MHC) class II alleles HLA DQA1*0501 and DQB1*0201 play an important role. To investigate whether an orthologous MHC class II region is involved in canine GSE, we undertook a linkage study in two large families of gluten sensitive Irish setter dogs. A total of 44 dogs in these pedigrees were genotyped for DQA1, DQB1 and C.2202 alleles, along with 30 unrelated healthy Irish setters. No genetic linkage between the DQ or C.2002 loci and GSE was detected. In contrast to CD, susceptibility to canine GSE does not appear to be determined by variation within the MHC class II gene cluster. Therefore, canine GSE may not be an appropriate model for CD, but nevertheless remains an important disease for advancing knowledge of pathological processes in the intestine.

Alleles↗
PubMed1998

Genetic polymorphism H131R of Fcgamma receptor type IIA (FcgammaRIIA) in a healthy Finnish population and in patients with or without platelet-associated IgG.

Patients (n=113) with histories of thrombocytopenia and with different profiles for platelet-associated IgG (PA-IgG) were subdivided according to the genetic polymorphism H131R in the Fcgamma receptor type IIA (FcgammaRIIA). PA-IgG was measured by the direct platelet immunofluorescence test (PIFT), and GP IIbIIIa and/or GP Ib-specific PA-IgG was investigated by a modified version of the direct monoclonal antibody-specific immobilization of platelet antigens (MAIPA) assay. As a control, the distribution of FcgammaRIIA polymorphism H131R was determined among 93 healthy Finnish blood donors. The frequencies for H131 and R131 were 0.56 and 0.44 (CI: 0.37-0.51), respectively, which did not differ significantly from those in other Caucasian populations. The distribution of the genotypes HH131, HR131 and RR131 in the patients and controls did not differ significantly. In the HH131 group, the PA-IgG was higher than in the RR131 group (p=0.082). Female patients with the genotype RR131 seemed to be younger than those with HH131 (p=0.065). Among the female patients, a significantly greater number were under 40 yr old in the RR131 group than in the HH131 group (p=0.0060). Within the RR131 group, the female patients were far younger than the male patients (median 29 vs. 61 yr; p=0.0021). The results point to the heterogeneity of immune thrombocytopenia, which may partly explain the poor predictive value of PA-IgG studies.

Adult↗
PubMed1997

Dual cerebral processing of elementary auditory input in children.

We compared event-related responses (ERPs) to non-attended frequent and intermittent auditory input in school-aged children and in young adults. In adults, both inputs elicited prominent auditory N100 responses at vertex. In children, intermittent stimulation evoked vertex responses with similar latency and refractoriness, whereas frequently delivered identical tones evoked responses on average at 240 ms. Sensitization of a separate neuronal population at 260-300 ms was obvious during intermittent stimulation in children. The dual behaviour, simultaneous 'habituation' of one neuronal population response and sensitization of another, may reflect the process of redirecting the attention and setting up a neuronal model. Furthermore, results suggest that a simplistic interpretation of developmental ERPs in which shortening of latencies represents maturation is insufficient.

Acoustic Stimulation↗
PubMed1997

Celiac patients predominantly inherit HLA-DPB1*0101 positive haplotype from HLA-DQ2 homozygous parent.

The DQA1*0501 and DQB1*0201 alleles (hereafter DQ2) confer genetic susceptibility to celiac disease (CD). Some studies have indicated that the DPB1, DMB, and TAP loci, that are located close to the DQ genes, could also together with DQ or independently confer genetic susceptibility to CD. Some others have claimed that these associations result merely from linkage disequilibrium, a hallmark of the MHC, that often makes the precise mapping of susceptibility genes difficult. To evaluate further the role of class II genes in CD, we analyzed segregation of DPB1 alleles in families with CD. In particular, we analyzed families where one of the parents was homozygous for the DQ2 risk allele but heterozygous for DPB1*0101, an allele claimed to be an additional risk allele. We reasoned that if DPB1*0101 would not play a role in CD, then patients should inherit the DQ2 haplotypes randomly from a homozygous parent. We here present evidence that, in all 6 informative families, those DQ2 positive haplotypes that also include the DPB1*0101 allele, rather than those without DPB1*0101, are predominantly segregated to the index patient from the parent homozygous for the DQ2 risk marker (p = 0.03 as compared to their healthy siblings). If confirmed in larger studies the results indicate that despite DQ2 other genes in or near the MHC may associate with CD.

Celiac Disease↗
PubMed1997

Effects of acute alcohol ingestion on heart rate variability in patients with documented coronary artery disease and stable angina pectoris.

The effects of acute alcohol intake (ethanol blood concentration 1.3 +/- 0.4%) on heart rate variability were evaluated with 24-hour Holter recordings in 20 patients with stable coronary artery disease in a juice-controlled experiment. In the frequency domain analysis, the high-, low-, and very low frequency components were significantly decreased after alcohol: these changes last longer than the elimination of alcohol.

Adult↗
PubMed1997

Divergent association of apolipoprotein E polymorphism with vascular disease in patients with NIDDM and control subjects.

We analysed a well-characterized group of 83 patients (43 men, 40 women; mean age +/- SEM: 65.5 +/- 0.6 years at the 10-year examination) with non-insulin-dependent (Type 2) diabetes mellitus (NIDDM) and in 123 control subjects (56 men, 67 women; mean age +/- 0.9 years) retrospectively for the relationship of apolipoprotein E (apo E) genotypes (E2/3, E3/3 vs E3/4, E4/4) to the incidence of clinical macrovascular disease and its risk factors and the incidence of microvascular complications of diabetes during the first 10 years of NIDDM, as well as carotid intima-media thickness measured by B-mode ultrasound at the 10-year examination. In patients with NIDDM, apo E4 genotype showed no relationship to clinical events or carotid intima-media thickness. However, in the control subjects with apo E4, the incidence of non-fatal myocardial infarction during the follow-up was increased (apo E4 positivity: 17.1%; apo E4 negativity 5.1%; p = 0.035) and they had higher common carotid intima-media thickness than those with apo E2/3 or apo E3/3 (1.15 +/- 0.05 mm vs 1.01 +/- 0.03 mm, p = 0.008). Apo E genotype groups showed no relationship to microvascular complications of diabetes, although control subjects with apo E4 positivity showed a higher frequency of microalbuminuria than those lacking apo E4. We conclude that apo E4 was a marker of vascular disease and increased atherosclerosis in non-diabetic subjects, whereas in the diabetic patients these relationships were absent. It is likely that NIDDM per se influences the vascular risk so overwhelmingly that the effects of other risk factors are obscured.

Alleles↗
PubMed1997

Relationship between EEG reactivity and neuropsychological tests in vascular dementia.

17 patients with vascular dementia (VaD) representing moderate to severe stage of the disease and 11 age-matched control subjects were examined with spectral analysis of EEG and a neuropsychological test battery comprising visual, praxic, verbal and memory functions as well as Mini-Mental Status test. VaD patients did not have less activity in the alpha band than control subjects, but the alpha amplitude ratio between eyes closed (EC) and eyes open (EO) situations (EC/EO ratio) was decreased in VaD patients, compared to controls. In VaD the variables of the awake background EEG with eyes closed (amplitude of alpha, beta, theta and delta activity; mean frequency) had only a few correlations to neuropsychological test scores. However, the (EC)/(EO) alpha ratio showed significant correlations with several neuropsychological variables in the temporo-occipital and centro-parietal derivations and some of these correlations were lateralized to the left or right hemisphere. Frontal EEG derivations with less alpha activity did not reveal any correlations to neuropsychological variables. We conclude that the dynamic EC/EO alpha ratio variable may be even more sensitive in the assessment of brain dysfunction in VaD than the background EEG variables.

Aged↗
PubMed1997

The ability of THA treatment to increase cortical alpha waves is related to apolipoprotein E genotype of Alzheimer disease patients.

In a previous study, we reported that Alzheimer disease (AD) patients with an apolipoprotein E (APOE) epsilon 4 allele (+ APOE4) show more severe loss of nucleus basalis (NB) cholinergic cells than patients without epsilon 4 alleles (-APOE4). The present study investigates the effects of a single oral administration of THA 25 or 50 mg on cortical spectral EEG activity in + (five APOE4/4, six APOE4/3) and -APOE4 (eight APOE3/3) AD patients. THA 25 mg had no significant effect on EEG activity in any AD patients. However, THA 50 mg increased alpha activity and alpha/theta ratio in -APOE4 patients. In contrast, THA 50 mg had no effect on EEG activity in + APOE4 patients. This result tentatively suggests that in AD patients APOE genotype may affect the response of cortical electrical arousal to cholinergic therapy that enhances the efficacy of presynaptic NB axons.

Aged↗
PubMed1997

THA disrupts mismatch negativity in Alzheimer disease.

The present study investigates the effects of 25 or 50 mg tetrahydroaminoacridine (THA), a cholinesterase inhibitor, on auditory mismatch negativity (MMN) event-related response in 19 patients with Alzheimer disease (AD). MMN is produced by the deviant tones representing passive attention and automatic detection of stimulus change. In an inattentive task condition, standard (85%) and deviant (15%) tones were represented in a random order with interstimulus interval of 1 s in separate blocks. THA 25 mg had no effect on MMN in AD patients. In contrast, THA 50 mg diminished MMN in AD subjects. The results suggests that acute treatment of AD subjects with a cholinesterase inhibitor disrupts the passive detection of change in an auditory input.

Aged↗
PubMed1997

Mutation-haplotype analysis of steroid 21-hydroxylase (CYP21) deficiency in Finland. Implications for the population history of defective alleles.

Congenital adrenal hyperplasia (CAH) due to steroid 21-hydroxylase deficiency is a common inherited defect of adrenal steroid hormone biosynthesis. Unusually for genetic disorders, the majority of mutations causing CAH apparently result from recombinations between the CYP21 gene encoding the 21-hydroxylase enzyme and the closely linked, highly homologous pseudogene CYP21P. The CYP21 and CYP21P genes are located in the major histocompatibility complex class III region on chromosome 6p21.3. We analyzed the mutations and recombination breakpoints in the CYP21 gene and determined the associated haplotypes in 51 unrelated Finnish families with CAH. They represent no less than half of all CYP21 deficiency patients in Finland. The results indicate the existence of multiple founder mutation-haplotype combinations in the population of Finnish CAH patients. The three most common haplotypes constituted half of all affected chromosomes; only one-sixth of the haplotypes represented single cases. Each of the common haplotypes was shown consistently to carry a typical CYP21 mutation and only in some cases was additional variation observed. Surprisingly, comparisons with previous published data revealed that several of the frequent mutation-haplotype combinations in Finland are in fact also found in many other populations of patients of European origin, thus suggesting that these haplotypes are of ancient origin. This is in clear contrast to many reports, including the present one, where a high frequency of de novo mutations in the CYP21 gene has been reported. In addition, two unique sequence aberrations in CYP21 (W302X and R356Q), not known to exist in the CYP21P pseudogene, were detected.

Adrenal Hyperplasia, Congenital↗
PubMed1997

A cluster of missense mutations at Arg356 of human steroid 21-hydroxylase may impair redox partner interaction.

Lesions in the gene encoding steroid 21-hydroxylase result in congenital adrenal hyperplasia, with impaired secretion of cortisol and aldosterone from the adrenal cortex and overproduction of androgens. A limited number of mutations account for the majority of mutated alleles, but additional rare mutations are responsible for the symptoms in some patients. A total of 11 missense mutations has previously been implicated in this enzyme deficiency. We describe two novel missense mutations, both affecting the same amino acid residue, Arg356. The two mutations, R356P and R356Q, were reconstructed by in vitro site-directed mutagenesis, the proteins were transiently expressed in COS-1 cells, and enzyme activity towards the two natural substrates, 17-hydroxyprogesterone and progesterone, was determined. The R356P mutant reduced enzyme activity to 0.15% towards both substrates, whereas the R356Q mutant exhibited 0.65% of normal activity towards 17-hydroxyprogesterone, and 1.1% of normal activity towards progesterone. These activities correspond to the degrees of disease manifestation of the patients in whom they were found. Arg356 is located in a region which recently has been implicated in redox partner interaction, by modelling the structure of two other members of the cytochrome P450 superfamily. Of the 11 previously described missense mutations, three affect arginine residues within this protein domain. With the addition of R356P and R356Q, there is a clear clustering of five mutations to three closely located basic amino acids. This supports the model in which this protein domain is involved in redox partner interaction, which takes places through electrostatic interactions between charged amino acid residues.

Adrenal Hyperplasia, Congenital↗
PubMed1997

Analysis of Tie receptor tyrosine kinase in haemopoietic progenitor and leukaemia cells.

We generated a panel of monoclonal antibodies against the extracellular domain of the Tie receptor tyrosine kinase and studied its expression in human haemopoietic and tumour cell lines and in samples from leukaemia patients. Most of the erythroblastic/megakaryoblastic (6/8), 2/7 myeloid and 3/6 B-lymphoblastic leukaemia cell lines were Tie-positive. The erythroblastic/megakaryoblastic leukaemia cell lines also expressed the related Tie-2/Tek gene and, surprisingly, its recently cloned ligand gene angiopoietin-1, which was located in chromosome 8q23.1. In addition, 16% of freshly isolated leukaemia samples were Tie positive. Peripheral blood mononuclear cells were Tie negative, but a few Tie positive cells were found in immunoperoxidase staining of mobilized peripheral blood stem cells. Long-term culture of isolated umbilical cord blood CD34+ Tie+ and CD34+ Tie- cells indicated that the Tie+ fraction contained a slightly higher frequency of cobblestone area forming cells (CAFC). Thus, Tie is expressed on haemopoietic progenitor cells and some leukaemic blasts. The coexpression of Tie-2 and angiopoietin-1 in megakaryoblastic leukaemia cell lines suggests the existence of an autocrine ligand/receptor signalling loop in these cells.

Angiopoietin-1↗
PubMed1997

Itraconazole decreases renal clearance of digoxin.

Itraconazole strongly interacts with some drugs metabolized by cytochrome P450 3A4, for example, felodipine and lovastatin, by inhibiting their metabolism. A concomitant use of itraconazole increases the serum concentrations of digoxin, although digoxin is excreted mainly unchanged in urine. To reveal the mechanism of the itraconazole-digoxin interaction, the effect of itraconazole on the serum concentrations and urinary excretion of digoxin was studied. Ten healthy volunteers in a double-blind, randomized, two-phase crossover study received either 200 mg itraconazole or placebo orally once a day for 5 days. On day 3, each volunteer ingested a single 0.5-mg oral dose of digoxin. The serum concentrations of digoxin and its excretion into urine as well as plasma concentrations of itraconazole were determined up to 72 hours after dosing. The mean area under the serum digoxin concentration-time curve, AUC(0-72), was approximately 50% higher (P < 0.001) during the itraconazole phase than during the placebo phase. In addition, the renal clearance of digoxin decreased about 20% (P < 0.01) by itraconazole. The increases in digoxin Cmax and T(1/2) by itraconazole were not statistically significant. The decreased renal clearance of digoxin during the itraconazole phase partially explains increased concentrations of digoxin during their concomitant use and may be caused by the inhibition of P-glycoprotein-mediated digoxin secretion in the renal tubular cells.

Administration, Oral↗
PubMed1997

Canine major histocompatibility complex genes DQA and DQB in Irish setter dogs.

Information about genetic variation within the canine major histocompatibility complex (MHC) class II genes is limited. In common with most other vertebrate species the canine MHC, or DLA, includes genes which are homologous to human DR, DQ, and DP. Recently, at least one functional DLA DQ gene-pair has been characterized, but so far systematic screening efforts have been lacking. In the present study, we sequenced both cDNA and genomic clones derived from DLA DQ genes of Irish setter dogs. This breed was of interest, since it shows a high prevalence of gluten sensitive enteropathy (GSE), which may be a useful animal model for celiac disease (CD) of man. Interestingly, few of the alleles found in Irish setters were identical to those previously detected in other breeds. Three novel DLA DQA and four novel DLA DQB alleles were discovered in 19 unrelated dogs. Strong association between certain HLA DQ alleles and CD of man prompted us to screen the DQ alleles of members of a family of gluten-sensitive Irish setter dogs. No haplotypes or alleles were shared by all affected dogs, but one frequent haplotype in this family was also detected in an unrelated gluten-sensitive Irish setter; this haplotype was absent in the healthy dogs. This observation warrants further investigation by screening the DQ alleles of a large population of unrelated gluten-sensitive Irish setters.

Alleles↗