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Biomedical subjects

S Aho

Publications and source records attributed to S Aho.

At least 19 recordsLinked to original sources
PubMed2003

[Early study of myocardial perfusion with MRI in revascularized infarcts].

The aim of this work is to study the regional myocardial perfusion by MRI early after revascularised myocardial infarction and to compare it with regional function. This prospective work has included 15 patients with acute first myocardial infarction that was precociously revascularised. A myocardial MRI was performed between D2 and D10 after myocardial infarction. The regional myocardial thickening was evaluated from cine-MRI sequences. For the study of myocardial perfusion, the first pass of the contrast agent was analysed from curves of the signal evolution versus time. The signal enhancement on late images acquired 10 minutes after the perfusion of the contrast agent was also evaluated. Among 384 studied myocardial segments, those with a normal gadolinium first pass curve had a relative thickening of 46 +/- 38%. The segments with a severely reduced first pass kinetic have a markedly reduced relative thickening (14 +/- 20%) in relation with myocardial hypoperfusion. The myocardial enhancement is frequently seen in the infarct territory and appears related to a reduced regional contractility. The myocardium is enhanced on late images in 12% of the normally perfused segments. These segments have a mildly reduced wall thickening (3.36 +/- 2.84 mm vs 4.42 +/- 2.83 mm). The segmental contractility in a reperfused myocardial infarction appears to depend both on the myocardial perfusion which reflects the microvascularisation and on the myocardial enhancement which is linked to myocardial structural alterations. MRI appears to be an adequate method to evaluate these abnormalities and allows an easy assessment of the no-reflow phenomenon, if present.

Adult↗
PubMed2002

Paraneoplastic pemphigus in children and adolescents.

BACKGROUND: Paraneoplastic pemphigus (PNP) is an autoimmune mucocutaneous disease associated with specific B-cell lymphoproliferative neoplasms. There has been an increasing number of individual reports in the childhood and adolescent population. OBJECTIVES: To examine the clinical and immunopathological features of PNP occurring in children and adolescents. PATIENTS AND METHODS: We analysed the clinical and immunopathological findings of 14 patients under the age of 18 years with a confirmed diagnosis of PNP. Sera from all patients were analysed by indirect immunofluorescence (IF) and immunoprecipitation for plakin autoantibodies, immunoblotting for detection of plectin autoantibodies, and enzyme-linked immunosorbent assay (ELISA) for the detection of desmoglein (Dsg) 1 and Dsg3 autoantibodies. RESULTS: Severe oral mucositis was observed in all patients, and lichenoid cutaneous lesions in eight of 14 patients. The average age at presentation was 13 years. Striking findings included: pulmonary destruction leading to bronchiolitis obliterans in 10 patients, association with Castleman's disease in 12 patients, and a fatal outcome in 10 patients. The underlying neoplasm was occult in 10 patients. Histological findings include lichenoid and interface dermatitis with variable intraepithelial acantholysis. Deposition of IgG and C3 in the mouth and skin by direct IF was not found in some cases, but indirect IF detected IgG autoantibodies in all cases. Immunoprecipitation revealed IgG autoantibodies against desmoplakin I, envoplakin and periplakin in all cases, and against desmoplakin II and the 170-kDa antigen in 13 and 10 patients, respectively. Dsg3 and Dsg1 autoantibodies were present in 10 and three patients, respectively, and plectin autoantibodies in 13 patients. CONCLUSIONS: PNP in children and adolescents is most often a presenting sign of occult Castleman's disease. It presents with severe oral mucositis and cutaneous lichenoid lesions. Serum autoantibodies against plakin proteins were the most constant diagnostic markers. Pulmonary injury appears to account for the very high mortality rates observed.

Adolescent↗
PubMed2001

[Epidemic of Staphylococcus aureus nosocomial infections resistant to methicillin in a maternity ward].

Methicillin-resistant Staphylococcus aureus (MRSA) nosocomial infections frequently occur in the hospital environment, but their incidence is less often observed in neonates. In the present investigation, seventeen cases were recorded over a nine-week period (two cases per week). Pulsed field gradient gel electrophoresis confirmed the clonal character of the strain. The hypothesis of manually-transmitted infection due to contamination from multiple sources was reinforced by the fact the epidemic persisted in spite of the elimination of the main human infectious source and an absence of risk factors determined by the case-control study. The role of environmental factors in the persistence of this outbreak of MRSA infection has been considered.

Adult↗
PubMed2001

Decrease in Candida albicans strains with reduced susceptibility to fluconazole following changes in prescribing policies.

This study was undertaken to identify prescribing policies likely to favour or limit fluconazole resistance within a clinical department. Fluconazole exposure within the infectious diseases and clinical haematology units was investigated, and data were compared with in vitro susceptibility of Candida albicans isolates obtained in these units. Fluconazole utilization was determined by the number of fluconazole treatment-days per 100 hospitalization days (penetration index). In the infectious diseases unit, separate evaluations for low-dose fluconazole (50 mg) prescribed as intermittent or prolonged treatment, and for higher-dosing schedules (fluconazole 200 mg) were made. Susceptibility of C. albicans isolates was surveyed in a broth microdilution assay by measuring the inhibitory concentration 50% (IC50). The penetration index (PI) for fluconazole 50mg declined from 1992 to 1977 in infectious diseases (P= 0.0048). In the meantime, total usage of fluconazole increased, due to increased prescribing of fluconazole 200 mg (P = 0.0724). The IC50 of C. albicans isolates tested in infectious diseases decreased between 1994 and 1996 from 7.33 mg/ml to 1.64 mg/ml (P = 0.0075). In clinical haematology, declines in C. albicans IC50 and fluconazole PI were not significant (P = 0.35 and P = 0.07, respectively). These data suggest that prolonged or repeated exposure to low-dose fluconazole, rather than total cumulative use, was associated with fluconazole resistance in the infectious diseases unit. Moreover, restoration of a normal ecology was observed when low-dose prolonged or intermittent prescriptions were reduced.

Analysis of Variance↗
PubMed2001

Assessment of chronic pain behaviour: reliability of the method and its relationship with perceived disability, physical impairment and function.

The aim of the present study was to develop a reliable assessment of pain behaviour performed during the execution of a range of functional assessment measures. For the initial reliability study 18 subjects (consecutive referrals) were assessed. Subjects were observed and videotaped during a variety of physical tasks and demonstrations of pain behaviour were recorded; the videotapes were scored by two independent observers on two occasions. The relationships between pain behaviour, distress and physical function and impairment were also investigated in a group of 51 patients with chronic back pain. Self-report of disability and pain intensity were assessed using the Finnish version of Oswestry disability questionnaire and the pain visual analogue scale (VAS). Depression and somatic perception were assessed using the modified Zung and modified somatic perception questionnaire. The Tampa scale for kinesiophobia was used to evaluate fear of movement and (re)injury. The results of the intra- and interobserver reliability study demonstrate good to excellent levels of agreement. The exception was facial expression (kappa 0.29), which was excluded from the final instrument. There was a strong correlation between pain behaviour and subjective pain report and disability (p < 0.01). The correlations between total pain behaviour and performance of physical function tasks is striking (p < 0.01). Subjective disability was analysed by means of multiple regression analysis. Pain measured on the VAS was the most important variable explaining 36% of the variance, pain behaviour and pain combined explained 48% of the variance for self reported disability. In conclusion, this functional videobased assessment of pain behaviour is a reliable measure of pain behaviour. The total scores for pain behaviour correlate with tasks that involve the back; tests involving upper limbs were not affected. This test is suitable for the assessment of those with pain problems specifically involving the back. Furthermore, in the group studied pain and pain behaviour were the two most important determinants of self-reported disability.

Adult↗
PubMed2001

Tissue distribution and cell type-specific expression of p120ctn isoforms.

Cadherin-based molecular complexes play a major role in cell-cell adhesion. At the adherens junctions the intracellular domain of cadherins specifically interacts with beta-catenin and p120ctn, members of the Armadillo repeat protein family. Differential splicing and utilization of the alternative translation initiation codons lead to many p120ctn isoforms. Two major p120ctn isoforms are expressed in mouse tissues. In this study we used indirect immunofluorescence to demonstrate significant tissue specificity in expression of the p120ctn isoforms. The short isoform is abundant at cell-cell adhesion junctions in epidermis, palatal, and tongue epithelia, in the ducts of excretory glands, bronchiolar epithelium, and in mucosal epithelia of esophagus, forestomach, and small intestine. In contrast, the long isoform, containing an amino terminus highly conserved within the p120ctn subfamily, is expressed at vascular-endothelial cell junctions in blood vessels, at cell-cell junctions in the serosal epithelium lining the internal organs, in choroid plexus of brain, in the pigment epithelium of retina, and in structures such as the outer limiting membrane of retina and intercalated discs of cardiomyocytes. The tissue- and cell type-specific expression of p120ctn isoforms suggests a role for the long p120ctn isoform in cell structures responsible for stable tissue integrity, compared to the role of the short isoform in cell-cell adhesion in the external epithelia with rapid turnover.

Animals↗
PubMed2000

Ubinuclein, a novel nuclear protein interacting with cellular and viral transcription factors.

The major target tissues for Epstein-Barr virus (EBV) infection are B lymphocytes and epithelial cells of the oropharyngeal zone. The product of the EBV BZLF1 early gene, EB1, a member of the basic leucine-zipper family of transcription factors, interacts with both viral and cellular promoters and transcription factors, modulating the reactivation of latent EBV infection. Here, we characterize a novel cellular protein interacting with the basic domains of EB1 and c-Jun, and competing of their binding to the AP1 consensus site. The transcript is present in a wide variety of human adult, fetal, and tumor tissues, and the protein is detected in the nuclei throughout the human epidermis and as either grainy or punctuate nuclear staining in the cultured keratinocytes. The overexpression of tagged cDNA constructs in keratinocytes revealed that the NH(2) terminus is essential for the nuclear localization, while the central domain is responsible for the interaction with EB1 and for the phenotype of transfected keratinocytes similar to terminal differentiation. The gene was identified in tail-to-tail orientation with the periplakin gene (PPL) in human chromosome 16p13.3 and in a syntenic region in mouse chromosome 16. We designated this novel ubiquitously expressed nuclear protein as ubinuclein and the corresponding gene as UBN1.

Adult↗
PubMed2000

The protein core of the proteoglycan perlecan binds specifically to fibroblast growth factor-7.

Perlecan is a multifaceted heparan sulfate proteoglycan that is expressed not only as an intrinsic constituent of basement membranes but also as a cell-surface and pericellular proteoglycan. Perlecan functions as a ligand reservoir for various growth factors that become stabilized against misfolding or proteolysis and acts as a co-receptor for basic fibroblast growth factor by augmenting high affinity binding and receptor activation. These biological properties are mediated by the heparan sulfate moiety. Rather little is known about the protein core's mediation of functions. We have recently discovered that fibroblast growth factor-7 (FGF7) binds to perlecan protein core and that exogenous perlecan efficiently reconstitutes FGF7 mitogenic activity in perlecan-deficient cells. In this report we examined the specific binding of FGF7 to various domains and subdomains of perlecan protein core. Using several experimental approaches including overlay protein assays, radioligand binding experiments, and the yeast two-hybrid system, we demonstrate that FGF7 binds specifically to the N-terminal half of domain III and to a lesser extent to domain V, with affinity constants in the range of 60 nM. Thus, perlecan protein core should be considered a novel biological ligand for FGF7, an interaction that could influence cancer growth and tissue remodeling.

Cells, Cultured↗
PubMed2000

Comparative genotyping of Candida albicans bloodstream and nonbloodstream isolates at a polymorphic microsatellite locus.

Molecular typing studies have shown that the predominant form of reproduction of Candida albicans is clonal and that, in a majority of situations, persistent or recurrent infections are due to a unique strain. Characterization of distinct subpopulations and correlation with clinical features may thus be important to understanding the pathogenesis of candidiasis. In a clonal model, a unique polymorphic marker may identify populations with different biological properties. We therefore compared 48 bloodstream isolates and 48 nonbloodstream matched strains of C. albicans at the elongation factor 3-encoding gene (CEF3) polymorphic microsatellite locus of C. albicans. Sizing of the alleles was performed by automated capillary electrophoresis. A new, 137-bp allele was characterized, and seven nondescribed combinations were observed, resulting in 15 and 11 distinct CEF3 profiles in bloodstream and control strains, respectively. Genotypes 126-135, 130-136, and 131-131 accounted for 60.4% of both bloodstream and control strains. Four bloodstream isolates but no control strains displayed the 135-135 combination. None of the other genotypes was present at an increased frequency in bloodstream isolates. Bloodstream and nonbloodstream strains of C. albicans thus have a heterogeneous structure at the CEF3 locus, with three major and multiple minor allelic combinations.

Alleles↗
PubMed1999

Human p120ctn catenin: tissue-specific expression of isoforms and molecular interactions with BP180/type XVII collagen.

Catenins, a family of structurally related proteins, are involved in epidermal keratinocyte cell-cell adhesion by interacting through their central Armadillo repeats with the intracellular domains of cadherins, transmembrane components of the adhesion junctions. p120ctn is a catenin expressed in different isoforms due to alternative splicing and multiple translation start sites. BP180 is a collagenous transmembrane protein (type XVII collagen) localized to hemidesmosomal attachment complexes in basal keratinocytes. In this study, we have delineated the molecular interaction between these two proteins utilizing the yeast two-hybrid system, which was confirmed by an in vitro protein-protein interaction assay. Specifically, it was shown that an amino-terminal segment of BP180 (aa. 13-25) contains the information necessary for binding to p120ctn isoforms 1-3, but not to the isoform 4, suggesting that the interacting domain is located immediately upstream from the Armadillo repeats and is encoded by exons 5 and 6, which are subject to alternative splicing only in a minority of transcripts. In addition to epidermal keratinocytes, p120ctn was shown to be expressed in a variety of adult and fetal tissues as well as in a number of human tumors. The expression pattern of various p120ctn transcripts, reflecting alternative splicing of the 5' exons, was strikingly similar between the corresponding adult and fetal tissues, while the expression patterns were discordant between certain tumors and their normal parental tissues, suggesting a functional role for the tissue-specific expression of the p120ctn isoforms. Finally, the tissue-specific expression of BP180 was shown to partially overlap with that of p120ctn, suggesting that the interaction of these two proteins may contribute to the modulation of cell-cell/matrix interactions in such tissues.

Alternative Splicing↗
PubMed1999

180-kD bullous pemphigoid antigen/type XVII collagen: tissue-specific expression and molecular interactions with keratin 18.

The 180-kD bullous pemphigoid antigen (BPAG2) is a hemidesmosomal transmembrane protein, also known as type XVII collagen. In this study, potential interactions of BPAG2 with other proteins expressed in epidermal keratinocytes were explored by yeast two-hybrid system using the amino-terminal intracellular domain of BPAG2 as a bait. Several independent interacting clones encoding keratin 18 (K18) were identified when the keratinocyte cDNA library, cloned into the yeast two-hybrid activation domain vector, was screened. The peptide sequence responsible for the interaction of BPAG2 was restricted to amino acids 15-25, and substitution of a valine residue in the middle of this sequence by a proline (V23P) by site-directed mutagenesis abolished the interaction. Further examination of the K18 sequences by restricted cDNA constructs in yeast two-hybrid system identified a carboxyl-terminal segment corresponding to helix 2B domain as critical for BPAG2 binding. The interaction of BPAG2/K18 was confirmed by an in vitro protein-protein interaction assay, which also confirmed that normal human keratinocytes express K18 in culture. The tissue specific expression of BPAG2 was first examined using a multi-tissue RNA blot. Human multiple tissue cDNA panels representing a variety of adult and fetal tissues as well as tumor cells were used as PCR-templates to study the expression patterns of both BPAG2 and K18. The results demonstrated significant level of expression of BPAG2, besides in epidermal keratinocytes, also in a variety of tissues with predominant epithelial component, such as mammary, salivary and thyroid glands, colon, prostate, testis, placenta, and adult and fetal thymus, as well as in colon, pancreatic and prostatic adenocarcinoma cell lines, and an ovarian carcinoma. As expected, K18 transcript is present in liver, pancreas, colon, placenta, and in fetal kidney. Collectively, the results suggest that BPAG2 has a relatively broad tissue distribution including specialized and simple epithelia, and that within the tissues such as colon and placenta, BPAG2 may have direct interactions with K18, a keratin characteristically expressed in a simple epithelia.

Adult↗
PubMed1999

Human periplakin: genomic organization in a clonally unstable region of chromosome 16p with an abundance of repetitive sequence elements.

Periplakin, a member of the plakin family of proteins, has been recently characterized by cDNA cloning, and the corresponding gene, PPL, has been mapped to human chromosome 16p13.3 (Aho et al., 1998, Genomics 48: 242-247). Periplakin has also been shown to serve as an autoantigen in a malignancy-associated autoimmune blistering disease, paraneoplastic pemphigus (Mahoney et al., 1998, J. Invest. Dermatol. 111: 308-313). In this study, we have elucidated the intron-exon organization of human PPL and characterized its promoter region. The flanking 5' sequences were rich in G and C ( approximately 80%) and included multiple AP2 sites and a SP1 site, while no canonical TATA or CCAAT sequences were found. The functionality of the upstream sequences (-709 to +135) as a promoter in cultured epidermal keratinocytes was detected by a CAT reporter gene, and a limited region (-382 to +135) showed activity in cultured dermal fibroblasts, attesting to cell-type specificity of the promoter. The genomic organization, including the intron-exon borders, was determined by direct nucleotide sequencing of human genomic P1 clones. Comparative analysis of cDNA and genomic sequences revealed that PPL consists of 22 exons, with the distribution of exons in PPL being consistent with that of other plakin genes: 21 small exons, separated by large introns, encode the amino-terminal globular domain, and 1 large exon encodes the entire rod and the tail domains. Characterization of four P1 clones spanning the PPL locus revealed multiple Alu repeats, 20 of them within 33 kb of the entirely sequenced segments (0.60/kb), in addition to numerous MIR and L1 elements. These repetitive elements could lead to the clonal instability detected throughout the genomic P1 clones and may give rise to the genomic rearrangements possibly underlying the paraneoplastic pemphigus.

Base Sequence↗
PubMed1998

cDNA cloning, mRNA expression, and chromosomal mapping of human and mouse periplakin genes.

A portion of the intracellular domain of Type XVII collagen, used as a bait in a yeast two-hybrid screen of an epidermal keratinocyte cDNA library, identified overlapping cDNA clones that showed a high degree of homology to envoplakin and other members of the plakin family of intermediate filament connector molecules. Subsequent cloning allowed identification of contiguous cDNA sequences with an open reading frame of 5268 bp encoding a putative polypeptide of 1756 amino acids with a computed molecular mass of 204.7 kDa. Northern analysis using these cDNA clones revealed a prominent band of approximately 6.5 kb in keratinocytes, which was barely detectable in fibroblasts. Multiple tissue RNA analysis showed that this protein is highly expressed in tissues with a prominent component of epithelial cells. This novel member of the plakin family was designated periplakin. The human gene (PPL) was mapped to the interval between D16S510 and D16S509 by radiation hybrid mapping, corresponding to chromosomal band 16p13. Murine ESTs having 97.2% amino acid identity to the human sequence were identified. Interspecific backcross mapping was used to place the murine periplakin gene (Ppl) 0.53 cM distal to marker D16mit32 on the proximal part of murine chromosome 16, close to the locus of mahoganoid (md), a mouse hair mutant. Mapping of this gene in human and mouse will allow evaluation of periplakin as a candidate locus for disorders of epithelial fragility, with or without other phenotypes.

Amino Acid Sequence↗