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J Partanen

Publications and source records attributed to J Partanen.

At least 73 records · Page 4Linked to original sources
PubMed1999

Genome scan for predisposing loci for distal interphalangeal joint osteoarthritis: evidence for a locus on 2q.

The genetic contribution to common forms of osteoarthritis (OA) is well established but poorly understood. We performed a genome scan, using 302 markers for loci predisposing to distal interphalangeal joint (DIP) OA. To minimize genetic heterogeneity in our study sample, we identified siblings with a severe, radiologically defined phenotype from the nationwide registers of Finland. In the initial genome scan, linkage analysis in 27 sibships gave a pairwise LOD score (Z) >1.00 with nine of the screening markers. In the second stage, additional markers and family members were genotyped in these chromosomal regions. On 2q12-q13, IL1R1 resulted in Z=2.34 at recombination fraction (theta) 0, allowing a dominant mode of inheritance. Association analysis of markers D2S2264, IL1R1, D2S373, and D2S1789 jointly provided some evidence for a shared haplotype among the affected individuals (P value of.012). Also, multipoint nonparametric linkage analysis yielded a P value of.0001 near the locus IL1R1 and P=.0007 approximately 20 cM telomeric near marker D2S1399, which, in two-point analysis, gave Z=1.48 (straight theta=. 02). This chromosomal region on 2q harbors the interleukin 1 gene cluster and, thus, represents a good candidate region for inflammatory and autoimmune disorders. Three additional chromosomal regions-4q26-q27, 7p15-p21, and Xcen-also provided some evidence for linkage, and further analyses would be justified to clarify their potential involvement in the genetic predisposition to DIP OA.

Adult↗
PubMed1999

HLA-DQ alleles and human papillomavirus DNA in adult-onset laryngeal papillomatosis.

Sixty-two patients with histologically confirmed adult-onset laryngeal papilloma were clinically examined; their HLA class II DQA1 and DQB1 alleles and the presence and type of human papillomavirus (HPV) in their laryngeal papilloma biopsies were determined by polymerase chain reaction-based methods. No differences in the DQA1 or DQB1 frequencies appeared between the patients as a group and the reference population. When the patients were divided into groups according to number of laryngeal procedures performed, no HLA association was noticed with any group, nor did the presence of HPV-6 or HPV-11 DNA in the laryngeal specimen correlate with HLA type. A suggestive association was found between the DQB1 *0501 allele and the 16 patients whose laryngeal biopsy was HPV-negative, but because of the small series, additional patients need to be studied. Earlier, the DQB1 *0501 allele was reported to be protective against cervical cancer, another HPV-associated disease.

Adolescent↗
PubMed1999

Celiac disease and markers of celiac disease latency in patients with primary Sjögren's syndrome.

OBJECTIVE: Many autoimmune diseases occur concomitantly with celiac disease. We investigated prospectively the occurrence of celiac disease and small-bowel mucosal inflammation in patients with primary Sjögren's syndrome. METHODS: A total of 34 patients with primary Sjögren's syndrome and 28 controls underwent small bowel biopsy. Villous morphology, jejunal intraepithelial lymphocytes, and mucosal HLA-DR were evaluated and DQA and DQB alleles, serum antiendomysial, and antigliadin antibodies were examined. RESULTS: Five (14.7%) of 34 Sjögren's syndrome patients were found to have celiac disease. The density of jejunal intraepithelial gammadelta+ T cells was increased in all celiac and in four nonceliac patients. All celiac patients, 69% of nonceliac Sjögren's syndrome patients, and 11% of control subjects showed enhanced HLA-DR expression (p < 0.001). HLA DQ2 was present in 19 (56%) patients with Sjögren's syndrome, including all five with celiac disease. CONCLUSIONS: The findings show a close association between Sjögren's syndrome and celiac disease. Even among nonceliac patients with primary Sjögren's syndrome, an ongoing inflammation is often present in the small bowel mucosa.

Autoimmune Diseases↗
PubMed1999

Molecular characterization of two mutations in platelet glycoprotein (GP) Ib alpha in two Finnish Bernard-Soulier syndrome families.

Bernard-Soulier syndrome (BSS) is a rare hereditary bleeding disorder and macrothrombocytopenia which is caused by a defect in the platelet glycoprotein Ib/IX/V (GP Ib/IX/V) complex, the receptor for von Willebrand factor and thrombin. Here we report the molecular basis of the classical form of BSS in two unrelated Finnish patients, both with a life-long history of severe bleeding. Flow cytometry and immunoblotting showed no expression of GP Ib/IX, GP Ib alpha, GP Ib beta or GP IX (less than 10%) in the patients' platelets. No expression of GP V (< 10%) was observed in propositus 1, but a residual amount was found in propositus 2 (24%). DNA sequencing analysis revealed that propositus 1 was compound heterozygous for a two-base-pair deletion at Tyr505(TAT) and a point mutation Leu129(CTC)Pro(CCC) in the GP Ib alpha gene. Propositus 2 was homozygous for the Tyr505(TAT) deletion. The nine relatives who were heterozygous for either of the mutations also had low levels of GP Ib alpha (74-90%). Hence, Bernard-Soulier patients homozygous or compound heterozygous for Tyr505(TAT) are severely affected. Interestingly, both mutations have independently been found in three other families in previous reports, suggesting their ancient age or mutational 'hot spot'.

Bernard-Soulier Syndrome↗
PubMed1999

Variant Bernard-Soulier syndrome due to homozygous Asn45Ser mutation in the platelet glycoprotein (GP) IX in seven patients of five unrelated Finnish families.

Bernard-Soulier syndrome (BSS), a rare bleeding disorder with macrothrombocytopenia, is caused by a defect of the platelet glycoprotein (GP) Ib/IX/V complex. Here we report a variant form of BSS in eleven patients of five unrelated families who originate from a particular area of Finland. The differential diagnosis from idiopathic thrombocytopenic purpura was difficult. Bleeding symptoms were epistaxis and haematomas debuting in childhood, but no spontaneous, severe bleeding episodes were reported. The platelet count varied from 43 to 81x10(9)/l. Screening the entire GP Ibalpha, GP Ibbeta, GP IX and GP V genes revealed a recurrent homozygous Asn45Ser mutation in GP IX in all probands. Flow cytometry showed markedly reduced expression of GP Ib (<10%), and only moderately reduced expression of GP IX (24-36%) and GP V (38-49%). The expression of subunits seemed to vary independently from the normal polymorphisms. Heterozygotes did not differ significantly from controls by their GP Ib/IX/V expression. Since the Asn45Ser mutation has also been reported in three other kindreds of northern and central European origin, this study reveals that instead of being a mutation hot spot, it may be ancient and scattered in Europe. Moderate, chronic thrombocytopenia should be carefully studied to diagnose variant BSS correctly from treatment resistant idiopathic thrombocytopenia.

Amino Acid Substitution↗
PubMed1999

Interaction of the TEK and TIE receptor tyrosine kinases during cardiovascular development.

TEK (TIE2) and TIE (TIE1) are structurally related receptor tyrosine kinases expressed in endothelial cells and their precursors. Genetic studies in the mouse have revealed essential functions of both receptors in angiogenic expansion of the vasculature during development. As previously shown, mouse embryos homozygous for a disrupted Tek allele die by day 10.5 of embryogenesis due to endocardial defects, hemorrhaging, and impaired vascular network formation. Furthermore, TIE is required cell autonomously for endothelial cell survival and extension of the vascular network during late embryogenesis. Here we have investigated possible redundancy in the TEK and TIE signalling pathways during vascular development. Vasculogenesis proceeds normally in embryos lacking both TEK and TIE, although such embryos die early in gestation of multiple cardiovascular defects. Mosaic analysis revealed an absolute requirement for TEK in the endocardium at E10.5, whereas TEK and TIE are dispensable for the initial assembly of the rest of the vasculature. In contrast, both receptors are required in the microvasculature during late organogenesis and in essentially all blood vessels of the adult. This analysis demonstrates essential functions for TEK and TIE in maintaining the integrity of the mature vasculature.

Animals↗
PubMed1999

Expression of HSP-65 in jejunal epithelial cells in patients clinically suspected of coeliac disease.

BACKGROUND: Coeliac disease (CD) can be classified both clinically and biologically an autoimmune disease. A close relationship obtains between heat shock proteins (HSPs) and numerous autoimmune diseases. HSPs are overexpressed when protecting the host against environmental insult. We sought here to establish whether dietary gluten is such a stress stimulus in patients clinically suspected of CD, and whether the expression of HSP-65 associates with densities of intraepithelial gammadelta+ T cells and/or with expression of mucosal HLA-DR. METHODS: Seventy-eight children with clinical suspicion of CD underwent a jejunal biopsy. Monoclonal antibodies were used to stain jejunal epithelial HSP-65, intraepithelial lymphocytes and mucosal HLA-DR. Serum IgA-class endomysial autoantibodies (EMA) were measured by an indirect immunofluorescence method. CD susceptibility HLA DQA1*0501 and DQB1*0201 alleles (HLA DQ2) were determined. RESULTS: Enhanced expression of epithelial cell mitochondrial HSP-65 was found in 80% (16/20) of coeliacs and in 24% (14/58) of children excluded for the disease, but in only 7% (2/28) of control subjects (p < 0.001, p = 0.049, respectively). Children with enhanced expression of HSP-65 had significantly higher gammadelta+ T cell densities than those with normal HSP-65 expression. A clear association between HSP-65 and serum IgA-class EMA were also ascertained in patients with normal jejunal mucosal morphology. HLA DQ2 positivity did not correlate with the HSP-65 expression. CONCLUSIONS: Gluten might be an environmental insult not only in CD patients but also in some patients excluded for the disease on biopsy. Enhanced expression of epithelial cell stress proteins might be an indicator of such an insult.

Adolescent↗
PubMed1999

Increased density of jejunal gammadelta+ T cells in patients having normal mucosa--marker of operative autoimmune mechanisms?

Both from a clinical and a biological point of view, coeliac disease can be classified among the autoimmune diseases, or one could suspect autoimmune mechanisms to be operative in the disease. The aim of the present study was to find evidence for mucosal markers of coeliac disease latency in patients clinically suspected but on routine biopsy excluded for the disease. Monoclonal antibodies were used to stain jejunal intraepithelial lymphocytes and mucosal HLA-DR. Serum IgA-class reticulin autoantibodies were measured by an indirect immunofluorescence and gliadin antibodies by an enzyme-linked immunosorbent assay method. The DQA1*0501 and DQB1*0201 alleles were determined. Twenty-seven of 107 consecutive patients had coeliac disease. Altogether 39 of 79 (49%) children with normal jejunal mucosa had an increased density of intraepithelial gammadelta+ T cells (> or = 4.4 cells/mm). IgA-class reticulin autoantibodies were positive in 18 (23%) of the children excluded for coeliac disease. The antibody positivity was mostly seen in patients carrying the DQAI 0501 and DQB1*0201 alleles. Also, reticulin autoantibody-positive children having normal jejunal mucosal morphology had significantly higher densities of intraepithelial gammadelta+ T cells than antibody negative ones. On 1.5-4.5 year follow-up four out of 18 (22%) children primarily excluded for coeliac disease showed mucosal deterioration and coeliac disease. Many patients clinically suspected of coeliac disease but having normal jejunal mucosa show markers of coeliac disease latency which may be gluten-induced indicating autoimmune mechanisms to be operative in the gut.

Adolescent↗
PubMed1998

Opposite phenotypes of hypomorphic and Y766 phosphorylation site mutations reveal a function for Fgfr1 in anteroposterior patterning of mouse embryos.

Intercellular communication is needed for both the generation of the mesodermal germ layer and its division into distinct subpopulations. To dissect the functions of fibroblast growth factor receptor-1 (FGFR1) during mouse gastrulation as well as to gain insights into its possible roles during later embryonic development, we have introduced specific mutations into the Fgfr1 locus by gene targeting. Our results show functional dominance of one of the receptor isoforms and suggest a function for the autophosphorylation of site Y766 in the negative regulation of FGFR1 activity. Y766F and hypomorphic mutations in Fgfr1 generate opposite phenotypes in terms of homeotic vertebral transformations, suggesting a role for FGFR1 in patterning the embryonic anteriorposterior axis by way of regulation of Hox gene activity.

Alleles↗
PubMed1998

The natural history of an HLA haplotype and its recombinants.

The presence of haplotype-specific recombination sites can be determined by analyzing the conservation of extended haplotypes in the population. This approach considers all meioses in the history of the population and requires the presence of characteristic markers that easily allow the identification of the haplotype or of its recombined segments. The recombination breakpoint can then be mapped by looking for shared alleles between haplotypes selected through the specific marker/s. We identified a rare perfect tandem duplication of a 145 base pair segment in the LTA promoter, which tags a B60 (B60D) haplotype. The duplication was detected in 16/90 B60+ Europeans, while absent in 101 B60+ Orientals. The conservation of the class I end and the extreme variability of the class II end suggested that the present-day B60D haplotypes originated from an ancestral haplotype by recombination events centromeric to the duplicated sequence. Through a fine mapping using markers of the HLA central region a preferential recombination site was localized in the 60 kilobase interval between TNFd,e, and D6S273/K11 Amicrosatellite loci (i.e., between LST1 and BAT3 genes). This site behaves as a potent recombination enhancer leading to fragmentation in most of the extant B60D haplotypes and can be considered responsible for their "instability". In the relatively recently founded Finnish population, where the LST1/BAT3 interval recombination has probably not yet had the chance to occur, a founder effect can explain the presence of a rare DP (DPB1(*)1601) allele in most B60D haplotypes in this population.

Base Sequence↗
PubMed1998

The effect of nursing on the brain activity of the newborn.

OBJECTIVE: To determine whether nursing influences brain activity in the newborn and whether there are differences in this respect between breast- or bottle-feeding and pacifier sucking. STUDY DESIGN: Fifty unselected volunteer mothers and their healthy full-term infants, under care in the maternity ward after delivery, served as subjects. Thirty mother-infant pairs were studied in relation to breast-feeding and 20 to bottle-feeding and pacifier sucking. Breast-fed infants were studied between the 1st and 7th day after delivery (mean +/- 2.7 days) and the infants in the bottle-fed group between the 1st and 8th day after delivery (mean +/- 3.3 days). METHODS: Qualitative and quantitative electroencephalogram (EEG), electrooculogram, submental electromyogram, and electrocardiogram were recorded before, during and after breast- and bottle-feeding and pacifier sucking. RESULTS: The amplitude of the EEG increased significantly during breast-feeding in the posterior cortical areas in both hemispheres with a slight predominance on the right. Bottle-feeding caused a similar, but somewhat less marked change. When the breast- and bottle-fed infants were compared, a significant difference was found in only one parameter of the 84 studied. Pacifier sucking had no significant effects on EEG activity. CONCLUSION: Nursing effects a change in the brain activity of the newborn. The cortical response to nursing is most probably a result of activation of the neurohumoral mechanisms related to hunger and satisfaction, including the hypothalamic, limbic, and other brain stem structures, which also regulate the sleep-wake cycle and modulate the level of cortical activity with respect to attention and vigilance.

Bottle Feeding↗
PubMed1998

HLA-DQ2-negative celiac disease in Finland and Spain.

Genetic susceptibility to celiac disease (CD) is strongly associated with DQA1*0501 and DQB1*02 (= DQ2). To study whether CD patients without DQ2 share other MHC class II or TNF alleles, we screened DQ2-negative patients in Finland and Spain. Twelve of 84 (14%) Finnish patients and 13 of 189 (6%) Spanish patients were negative for DQ2. We observed that all but two of altogether 25 DQ2-negative patients had the DR4 DQ8 haplotype, or either DQA1*0501 or DQB1*02 alone. Also, all but three were positive for DRB4*01. The only patients without any of these alleles were both positive for DR 13. There was a clear difference between Finland and Spain: Ten (83%) of the 12 Finnish DQ2-negative patients but only five (38%) of the 13 Spanish patients had DRB1*03, DQA1*03, DQB1*0302 (= DQ8) alleles. Of the Spanish patients, eight (62%) had DQB1*02 without DQA1*0501 and three (23%) had DQA1*0501 without DQB1*02. None of the TNF, TAP, or DPB1 alleles was found to be significantly associated with CD. Our results indicate that in addition to the DQ2 heterodimer, the other major risk alleles for CD are DR4 DQ8, and either DQA1*0501 or DQB1*02 alone. Patients without these alleles appear to be very rare, only two (0.7%) were identified in altogether 253 patients tested.

Adolescent↗
PubMed1998

Tetrahydroaminoacridine improves the recency effect in Alzheimer's disease.

We investigated the effects of a single administration of tetrahydroaminoacridine (25 and 50 mg, orally), a cholinesterase inhibitor, on memory function in Alzheimer's disease patients. The recall of memory items from the end of the word list (recency effect) was improved in a subgroup of Alzheimer's disease patients (responders 10 out of 28) by tetrahydroaminoacridine 50 mg. However, tetrahydroaminoacridine 50 mg had no effect on the recall of those words from the beginning or middle of the list. Tetrahydroaminoacridine did not markedly improve non-verbal delayed matching to sample or paired associates learning in any of the Alzheimer's disease patients. The "responders" performed better than the "non-responders" in tests measuring memory and frontal functions. The responders had less severe hippocampal atrophy and less prefrontal blood flow defect, and had a lower frequency of the apolipoprotein E4 allele than the "non-responders". These results suggest that acute tetrahydroaminoacridine treatment may stimulate the recency effect, and that a severe dysfunction of hippocampus and prefrontal regions blocks this effect of tetrahydroaminoacridine on short-term memory performance.

Aged↗
PubMed1998

Tibial muscular dystrophy--from clinical description to linkage on chromosome 2q31.

A genome scan with highly polymorphic markers has established linkage for tibial muscular dystrophy (TMD), a recently described late onset distal myopathy, to a novel myopathy locus on chromosome 2q31. The mode of inheritance in TMD is autosomal dominant and the typical symptom of ankle dorsiflexion weakness appears in the fourth to seventh decade. Weakness of lower leg muscles is slowly progressive eventually causing a moderate foot drop. Overall disability usually remains mild even in elderly patients and walking ability is preserved throughout the patient's lifetime. The main target of the disease, the tibial anterior muscle, shows progressive dystrophic changes with rimmed vacuoles at the early stages and complete replacement pathology at later stages of the disease. The linkage studies in four different TMD families revealed a common core haplotype with a set of markers on the chromosome 2q31 locus. This indicates one major ancient founder mutation for TMD in Finland. There is one superior candidate gene on the 2q31 locus, the gene encoding a giant protein titin, expressed in heart and skeletal muscle.

Chromosomes, Human, Pair 2↗
PubMed1998

Circulating T lymphocyte subsets in coeliac disease (CoD) patients and healthy family members.

Increased proportions of circulating antigen-primed CD45RO+ TCR gammadelta cells have been found in untreated CoD patients. As certain immunological features are now found in both CoD and healthy persons carrying the HLA DQ2 heterodimer, we sought to establish whether healthy members of the families of CoD patients who are positive for HLA DQ2 and also have increased densities of TCR gammadelta intraepithelial lymphocytes (IEL) in their small bowel mucosa have elevated levels of circulating TCR gammadelta memory cells. Peripheral blood T cells were analysed by flow cytometry in 22 patients with CoD and 16 healthy family members. Untreated CoD patients had higher percentages of circulating CD45RO+ TCR gammadelta cells and CD45RO+ Vdelta1+ cells than healthy family members. On the other hand, the amount of circulating Vdelta1+ lymphocytes was lower in patients with CoD compared with healthy family members. In contrast, no differences were found between HLA DQ2+ and HLA DQ2- healthy family members in respect of circulating TCR gammadelta cell subsets. The change in circulating TCR gammadelta cell subsets found in patients with CoD is thus a consequence of an ongoing immunological process which diminishes on a gluten-free diet rather than a phenomenon directly caused by DQ2. These changes in peripheral blood are not found in healthy individuals who have the same HLA alleles DQA1*0501 and DQB1*0201 encoding the HLA DQ2 and who also have increased densities of TCR gammadelta IEL in their otherwise normal jejunal mucosa.

Adolescent↗
PubMed1998

Salbutamol inhalation has no effect on myocardial ischaemia, arrhythmias and heart-rate variability in patients with coronary artery disease plus asthma or chronic obstructive pulmonary disease.

OBJECTIVES: Inhaled beta-2 agonists raise heart rate, systolic blood pressure and contractility, all of which cause an increase in oxygen consumption of the heart. We performed a study on the influence of inhaled salbutamol on myocardial ischaemia, rhythm, and heart rate variability as assessed by Holter monitoring of 24 patients with coronary artery disease (CAD) and clinically stable asthma or chronic obstructive pulmonary disease (COPD). DESIGN: In hospital the patients received 0.2 mg (hour 1), 0.4 mg (hour 6), 0.8 mg (hour 13) of salbutamol with a metered-dose inhaler and a spacer, and 5 mg (hour 25) with a nebulizer; symptoms, peak expiratory flow (PEF), 30-h Holter monitoring, and blood pressure (BP) were recorded. The study parameters were compared for the hour preceding and following each dose of salbutamol. RESULTS: No cardiac symptoms were associated with salbutamol inhalation. PEF increased after all doses (P < 0.005). A dose of 0.2 mg salbutamol induced no changes in heart rate, whereas dose of 0.4 mg increased heart rate from a mean of 75 +/- 13 to 79 +/- 14 beats min-1 (P < 0.005), and a dose of 0.8 mg from 76 +/- 14 to 78 +/- 15 beats min-1 (P < 0.05). No changes in systolic BP appeared after any dose of salbutamol. The diastolic BP was lowered after 0.8 mg of salbutamol from 86 +/- 12 to 82 +/- 10 mmHg (P < 0.05). The 5 mg of nebulized drug provoked no significant changes in heart rate or BP. Myocardial ischaemia, heart rate variability and ventricular arrhythmias remained unaltered with all doses. CONCLUSIONS: The commonly used doses of inhaled or nebulized salbutamol induced no acute myocardial ischaemia, arrhythmias or changes in heart rate variability in patients with CAD and clinically stable asthma or COPD.

Administration, Inhalation↗