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Biomedical subjects

M Uusitalo

Publications and source records attributed to M Uusitalo.

At least 19 recordsLinked to original sources
PubMed2005

Enrichment of the R77C alpha-sarcoglycan gene mutation in Finnish LGMD2D patients.

Limb-girdle muscular dystrophy 2D (LGMD2D) is caused by mutations in the alpha-sarcoglycan gene (SGCA). The most frequently reported mutation, 229CGC>TGC (R77C) in exon 3 of SGCA, results in the substitution of arginine by cysteine. We present here the clinical, immunohistochemical, and genetic data of 11 Finnish patients with LGMD2D caused by mutations in SGCA. Mutational analysis showed 10 patients homozygous and 1 compound heterozygous for R77C. A wide spectrum of SGCA mutations has been reported previously. Our results show an enrichment of R77C in Finland, further underlined by the observed carrier frequency of 1 per 150. According to the annual birth rate of approximately 60,000 in Finland, one LGMD2D patient with a homozygous mutation is expected to be born every 1 or 2 years on average. The presence of an ancient founder mutation is indicated by the fact that all patients shared a short common haplotype extending > or = 790 kilobases. Our results emphasize the need to include the SGCA gene R77C mutation test in routine DNA analyses of severe dystrophinopathy-like muscular dystrophies in Finland, and suggest that the applicability of this test in other populations should be studied as well.

Adolescent↗
PubMed2001

Reconstruction with rectus abdominis myocutaneous free flap after orbital exenteration in children.

OBJECTIVE: To present a 1-stage technique for orbital reconstruction after exenteration with the use of myocutaneous rectus abdominis free flap in children. SURGICAL TECHNIQUE: After orbital exenteration, a myocutaneous rectus abdominis free flap with long vascular pedicle is harvested from the abdomen. The flap is transferred to the orbit and the vascular pedicle is passed through an opening made in the lateral orbital wall, where it is anastomosed to superficial temporal vessels. The skin of the flap is trimmed to correspond to the eyelid defect and the incisions are closed. METHODS: After informed consent was obtained, 2 children, 3 and 8 years old, underwent orbital reconstruction with a rectus abdominis free flap after exenteration for orbital rhabdomyosarcoma and orbital osteosarcoma in the setting of retinoblastoma. RESULTS: This technique allowed easy postoperative wound care. Viability of the flap was excellent. The technique provided sufficient volume to fill the orbit, with improved aesthetic results and minimal donor site deformity. CONCLUSIONS: The postoperative care and aesthetic outcome in patients with rectus abdominis free flap after exenteration are much improved over those provided with traditional surgical techniques. This primary reconstruction is recommended for any patient requiring orbital exenteration, but particularly for pediatric patients who tolerate debridement of traditional exenteration sites poorly.

Child↗
PubMed2001

The HNK-1 carbohydrate epitope in the eye: basic science and functional implications.

The HNK-1 carbohydrate epitope is part of many cell membrane and extracellular matrix molecules. It has been implicated in cell to cell and cell to extracellular matrix adhesion, and antibodies to the HNK-1 epitope are emerging as a versatile tool in eye research. They have been used to identify a novel cell type in the human eye, the subepithelial matrix cells that reside in the inner connective tissue layer (ICTL) of the ciliary body. Although these cells resemble fibroblasts in ultrastructure, they form a distinct cell population that differs in its antigenic profile from fibroblasts of other tissues. These cells are associated with the elastic fiber system of the ICTL. Other structures in the human eye that harbor the HNK-1 epitope in a nonrandom pattern are the ciliary and iris epithelia, the zonular lamella, the lens capsule, the retina, glial cells of the optic and ciliary nerves, and scleral fibroblasts. The HNK-1 epitope in the eye appears early during embryonic development and is phylogenetically conserved, but many interspecies differences exist in its distribution. The role of the HNK-1 epitope may be to structurally stabilize the ciliary body and the retina, and to participate in zonular attachments. The HNK-1 epitope has been linked with many common eye diseases. The subepithelial matrix cells seem to be susceptible to undergo irreversible damage as a result of glaucoma, thermal injury, and tissue compression. This epitope has proved to be useful in identifying intraocular deposits of exfoliation syndrome. It can explain the adhesiveness of exfoliation material. Intraocular exfoliation material differs in HNK-1 immunoreactivity from the extraocular fibrillopathy of exfoliation syndrome and its presence in fellow eyes also argues against the concept of unilateral exfoliation syndrome. The HNK-1 epitope is found in the extracellular matrix of secondary cataract and anterior subcapsular cataract, and it may contribute to their pathogenesis. Finally, the HNK-1 epitope can be used to trace neuroepithelial derivatives of the optic vesicle in developmental anomalies and in tumors of the eye. Eventual identification of molecules that bear the HNK-1 epitope in the eye will likely shed light on many aspects of ocular physiology and pathobiology

Animals↗
PubMed2000

Immunolocalization of transforming growth factor-beta1 and tenascin in human secondary cataract.

PURPOSE: This study was carried out to investigate the distribution of transforming growth factor-beta1 (TGF-beta1) and the extracellular matrix (ECM) glycoprotein tenascin in secondary cataract and anterior subcapsular cataract. METHODS: Twenty-four pseudophakic human eyes with secondary cataract, obtained at autopsy 1 d to 10 yr (mean 2.4 yr) after cataract surgery, were studied. Additionally, a specimen from an anterior subcapsular cataract was included. Immunohistochemistry was used to localize TGF-beta1 and tenascin in secondary cataract and in anterior subcapsular cataract. RESULTS: Polyclonal antibody to TGF-beta1 immunolabelled spindle-shaped cells in the plaques of secondary cataract in all eyes. Instead, the cells present in Soemmering's ring cataract were not labelled. The ECM in the plaques of secondary cataract was immunoreactive for tenascin in all eyes. In anterior subcapsular cataract spindle-shaped cells and ECM showed similar immunoreactivity. CONCLUSION: Spindle-shaped cells that are immunolabelled with TGF-beta1 and ECM showing tenascin-like-immunoreactivity are present in secondary cataract and in anterior subcapsular cataract, thus implicating a possible role in secondary cataract.

Aged↗
PubMed2000

Search for autoantibodies against the HNK-1 carbohydrate epitope in the human eye in intermediate uveitis.

PURPOSE: Molecules bearing the immunogenic HNK-1 epitope are present in the inner connective tissue layer and epithelia of the ciliary body. We investigated whether autoantibodies to these molecules can be detected in patients with intermediate uveitis, which affects the ciliary body. METHODS: Serum was collected from 9 patients with intermediate uveitis, and from 6 controls with idiopathic iritis and 3 controls with sarcoid uveitis, representing nongranulomatous and granulomatous uveitis, respectively. The sera were used as polyclonal antibodies to immunostain 3 formalin-fixed, paraffin-embedded normal human donor eyes by the avidin-biotinylated peroxidase complex method. RESULTS: No immunostaining in the ciliary body could be detected using the sera from patients with intermediate uveitis or from the controls. Serum within blood vessels was nonspecifically immunolabelled with the secondary anti-human anti-serum. CONCLUSION: No autoantibodies against the HNK-1 epitope or other antigens of the ciliary body could be demonstrated in patients with intermediate uveitis. It is unlikely that such autoantibodies against the HNK-1 epitope have a role in intermediate uveitis.

Adolescent↗
PubMed1998

Obliterative lesions in small airways in an immunosuppressed porcine heterotopic bronchial allograft model.

We have recently developed a heterotopic large-animal model for research into obliterative lesions in small airways caused by allograft rejection. In this model, the small airways of subcutaneously implanted allografts gradually obliterate, whereas autografts remain patient. Twenty lung fragments and 20 segments of bronchi were implanted in domestic pigs weighing 20 kg from non-related donors. The histology of five animals receiving daily cyclosporine A (CsA) (10 mg/kg), azathioprine (2 mg/kg) and methylprednisolone (20 mg), Group C, was compared with that of six animals without immunosuppression, Group A. Four animals received monotherapy with CsA (10 mg/kg) or methylprednisolone (3 mg/kg). The histological findings were graded from 0 to 3 on the basis of implants harvested repeatedly over 3 months. Epithelial destruction and bronchial obliteration was rapid and permanent in all the allografts. Inflammation and fibrosis of the bronchial wall was less prominent in Group C than in Group A and the onset of fibrosis was delayed. Cartilage degeneration and pericartilagineous inflammation were significantly less severe in Group C (P < 0.05). Monotherapy was less potent than triple therapy. This large-animal model is useful for studying the effects of immunosuppressive drugs on obliterative airway disease.

Animals↗
PubMed1998

Structure, development and function of cytoskeletal elements in non-neuronal cells of the human eye.

The cytoskeleton, of which the main components in the human eye are actin microfilaments, intermediate filaments and microtubules with their associated proteins, is essential for the normal growth, maturation, differentiation, integrity and function of its cells. These components interact with intra- and extracellular environment and each other, and their profile frequently changes during development, according to physiologic demands, and in various diseases. The ocular cytoskeleton is unique in many ways. A special pair of cytokeratins, CK 3 and 12, has apparently evolved only for the purposes of the corneal epithelium. However, other cytokeratins such as CK 4, 5, 14, and 19 are also important for the normal ocular surface epithelia, and other types may be acquired in keratinizing diseases. The intraocular tissues, which have a relatively simple cytoskeleton consisting mainly of vimentin and simple epithelial CK 8 and 18, differ in many details from extraocular ones. The iris and lens epithelium characteristically lack cytokeratins in adults, and the intraocular muscles all have a cytoskeletal profile of their own. The dilator of the iris contains vimentin, desmin and cytokeratins, being an example of triple intermediate filament expression, but the ciliary muscle lacks cytokeratin and the sphincter of the iris is devoid even of vimentin. Conversion from extraocular-type cytoskeletal profile occurs during fetal life. It seems that posttranslational modification of cytokeratins in the eye may also differ from that of extraocular tissues. So far, it has not been possible to reconcile the cytoskeletal profile of intraocular tissues with their specific functional demands, but many theories have been put forward. Systematic search for cytoskeletal elements has also revealed novel cell populations in the human eye. These include transitional cells of the cornea that may represent stem cells on migration, myofibroblasts of the scleral spur and juxtacanalicular tissue that may modulate aqueous outflow, and subepithelial matrix cells of the ciliary body and myofibroblasts of the choroid that may both participate in accommodation. In contrast to the structure and development of the ocular cytoskeleton, changes that take place in ocular disease have not been analysed systematically. Nevertheless, potentially meaningful changes have already been observed in corneal dystrophies (Meesmann's dystrophy, posterior polymorphous dystrophy and iridocorneal endothelial syndrome), degenerations (pterygium) and inflammatory diseases (Pseudomonas keratitis), in opacification of the lens (anterior subcapsular and secondary cataract), in diseases characterized by proliferation of the retinal pigment epithelium (macular degeneration and proliferative vitreoretinopathy), and in intraocular tumours (uveal melanoma). In particular, upregulation of alpha-smooth muscle actin seems to be a relatively general response typical of spreading and migrating corneal stromal and lens epithelial cells, trabecular cells and retinal pigment epithelial cells.

Cytoskeletal Proteins↗
PubMed1998

Small airway obliteration in a new swine heterotopic lung and bronchial allograft model.

BACKGROUND: We studied a heterotopic large-animal model with obliterative airway lesions caused by allograft rejection. METHODS: Lung fragments (1 cm3) with airways (LB), and 1 to 2 mm diameter bronchi alone (B) were implanted subcutaneously in 11 domestic piglets weighing 20 kg. Six animals each received 40 implants from nonrelated donors without immunosuppression (group A). Another 5 animals had autograft implants (group U). The implants were harvested consecutively for histologic analysis over 3 months in group A and 6 months in group U. RESULTS: In group U, the initial ischemia caused mild to moderate epithelial damage with moderate metaplasia but with a return to normal ciliary epithelium within 1 month. Transient mild luminal obliteration with granulation tissue and mononuclear cells was observed during the first weeks, but after 4 weeks the lumen was patent and filled with mucus. In the bronchial wall, moderate fibrosis developed in LB implants, whereas mild fibrosis was seen in B implants. In group A, the epithelium was totally absent by 2 weeks, and mild inflammation, fibrosis, and destruction of the cartilage with pericartilaginous mononuclear accumulation were observed in the bronchial wall. Small airways were gradually obliterated between days 7 and 21, initially by granulation tissue and mononuclear cells and later by progressive fibrosis. CONCLUSIONS: In this model, autografted airway implants stayed patent for at least 6 months, whereas total luminal obliteration histologically resembling obliterative bronchiolitis developed in allografts within 21 days. Because small airways, including bronchioli, can be transplanted with the use of this model, it may be useful for research into the causes of airway obliteration, which may be relevant to the pathogenesis of obliterative bronchiolitis in lung recipients.

Animals↗
PubMed1997

Cell types of secondary cataract: an immunohistochemical analysis with antibodies to cytoskeletal elements and macrophages.

BACKGROUND: The study was carried out to identify cell types of secondary cataract after extracapsular cataract extraction and implantation of an intraocular lens. METHODS: Twenty-five formalin-fixed, paraffin-embedded pseudophakic human eyes with secondary cataract, obtained at autopsy, were studied and compared to a specimen from an anterior subcapsular cataract with a panel of six monoclonal antibodies (MAbs, to vimentin, cytokeratin (CK) 8 and 18, desmin, alpha-smooth muscle actin, and the CD68 epitope of macrophages by the avidin-biotinylated peroxidase complex (ABC) method. RESULTS: MAb Vim 3B4 to vimentin immunolabeled spindle-shaped cells in 16 of 17 central plaques of secondary cataract as well as cells in all 16 Soemmering's ring cataracts. Spindle-shaped cells reacted with MAb CAM 5.2 to CK 8 in 13 of 18 eyes, but only one specimen was labeled with MAb CY-90 to CK 18. No immunoreaction was seen with MAb D33 to desmin, whereas MAb 1A4 to alpha-smooth muscle actin immunolabeled spindle-shaped cells in 15 of 18 plaques of secondary cataract. Macrophages were seen with MAb PG-M1 in 13 of 19 secondary cataracts. In the anterior subcapsular cataract, spindle-shaped cells under a wrinkled but otherwise intact capsule reacted with MAb Vim 3B4 to vimentin, MAb CAM 5.2 to CK 8, and MAb 1A4 to alpha-smooth muscle actin. CONCLUSION: Spindle-shaped cells in secondary and anterior subcapsular cataracts react with antibodies to vimentin, CK 8 and alpha-smooth muscle actin, suggesting them to be metaplastic epithelial cells that derive from the lens epithelium. alpha-Smooth muscle actin persists in them at least 10 years postoperatively, but CK 8 starts to disappear after 3 years. Macrophages are one possible modulator of this transdifferentiation.

Aged↗
PubMed1997

The HNK-1 epitope in the pseudophakic and aphakic eye and secondary cataract.

PURPOSE: To search for changes in the presence and distribution of the cell-adhesion-related HNK-1 carbohydrate epitope after cataract extraction. METHODS: Twenty-five pseudophakic and two aphakic human autopsy eyes and, for comparison, one anterior subcapsular cataract obtained at surgery were studied with monoclonal antibodies (MAbs) HNK-1 and NC-1 to the HNK-1 epitope using the avidin-biotinylated peroxidase complex method. RESULTS: MAbs to the HNK-1 epitope constantly immunolabelled the inner connective tissue layer of the ciliary body in all pseudophakic and aphakic eyes studied. The distribution of the immunoreaction was similar to that reported for normal eyes. They also labelled the extracellular matrix in each of 18 plaques of secondary cataract on the posterior capsule, in each of 13 plaques at the rim of the capsular bag, and in the anterior subcapsular cataract. Bladder cells in each of 16 Soemmering's rings remained unlabelled. CONCLUSION: The distribution of the HNK-1 epitope in the ciliary body does not appreciably change after cataract extraction, although the accommodative demand of the eye is altered. Its presence in an anterior subcapsular cataract suggests that the epitope may be locally produced by lens epithelial cells also in secondary cataract. The epitope is associated with cell adhesion and migration, both of which may play a role in the pathogenesis of secondary cataract.

Aged↗
PubMed1997

Detection of acute rejection by 133Xe radiospirometry after single lung transplantation in an experimental porcine model.

Aim of this experimental study was to evaluate acute rejection in a porcine single-lung transplantation model by using 133Xe radiospirometry. Left lung allotransplantation was performed on 11 and autotransplantation on 5 piglets. Postoperative monitoring consisted of 77 radiospirometric examinations with assessments of regional perfusion (Qtx), ventilation (V) and ventilation/perfusion ratio (V/Qtx). Results were compared with transbronchial biopsy. A significant decrease in Qtx (p < 0.01) and an increase in V/Qtx (p < 0.01) were observed during acute rejection, whereas V remained unaltered. These changes were significant already at minimal rejection (grade A1), and further increased at moderate rejection (grade A3). Sensitivity and specificity of Qtx were 82 and 74%, and those of V/Qtx, 87 and 65%. 133Xe radiospirometry detects even minimal acute rejection after single lung transplantation.

Acute Disease↗
PubMed1997

Acute rejection diagnosed with computed tomography in a porcine experimental lung transplantation model.

The role of computed tomography (CT) in the diagnosis of acute rejection was studied in an experimental lung transplantation model, with 15 left lung allotransplantations and six autotransplantations performed on piglets weighing 16-24 kg. There were 31 episodes of acute rejection. In the allotransplantation group the development of acute rejection was monitored 115 times with CT, transbronchial biopsy (TBB) and bronchoalveolar lavage (BAL). The stages of acute rejection were 1) ill-defined centrilobular micronodules or minimal patchy ground-glass opacities. 2) dense, small-nodular infiltration or extensive ground-glass opacities, and bronchial wall thickening. 3) lung volume loss and dense, patchy ground-glass opacities and 4) consolidation of the lung. In the autotransplantation group monitoring was done 42 times. After allotransplantation, TBB and BAL suggested rejection 60 times and infection 23 times. CT had 86.7% sensitivity and 85.6% specificity. During the first month these figures were, respectively, 71.4% and 84.2%. Rising histologic grade was associated with increasing stage of acute rejection on CT, which thus proved to be a sensitive and specific method for diagnosing acute rejection of lung transplant.

Acute Disease↗
PubMed1997

The HNK-1 epitope and the elastic fiber system of the human ciliary body. An immunoelectron microscopic study.

PURPOSE: To localize at the electron microscopic level the cell adhesion-related HNK-1 carbohydrate epitope in the inner connective tissue layer (ICTL) of the human ciliary body. METHODS: Seven specimens representing the pars plicata (age range, 12 to 86 years) and three specimens representing the pars plana (age range, 29 to 71 years) of the ciliary body were sampled at death from eight normal human eyes. Three additional specimens from the pars plicata were taken from three eyes with exfoliation syndrome (age range, 78 to 81 years). All specimens were embedded in LR white resin and studied by postembedding immunogold labeling using two monoclonal antibodies (mAbs) HNK-1 and NC-1 in detecting the HNK-1 epitope. RESULTS: In the ICTL of the pars plicata and the pars plana, mAbs HNK-1 and NC-1 constantly bound to the surface of fibroblast-like cells present in the subepithelial connective tissue matrix. The immunoreaction was localized along the cell membrane, both around the cell body and around its long, slender cytoplasmic processes. Long microfibrillar bundles, which consisted of approximately 10-nm thick microfibrils in close association with these subepithelial matrix cells and elastic fibers, were also labeled. The periphery of elastic fibers was likewise immunolabeled for the HNK-1 epitope. The reaction pattern was essentially the same, regardless of age and presence or absence of exfoliation syndrome. CONCLUSIONS: At the ultrastructural level, the HNK-1 epitope in the ICTL is a common denominator to the subepithelial matrix cells, microfibrillar bundles, and elastic fibers. This suggests that the subepithelial matrix cells secrete this epitope, and that molecules hearing it may be involved in joining these connective tissue elements that structurally stabilize the ciliary body.

Adolescent↗
PubMed1997

Autopsy analysis of clinically unilateral exfoliation syndrome.

PURPOSE: To study the pathogenesis of clinically unilateral exfoliation syndrome by localizing exfoliation deposits in involved and fellow eyes during autopsy. METHODS: The formalin-fixed and paraffin-embedded involved and fellow eyes were obtained at autopsy from five patients (age range, 72 to 88 years) with clinically unilateral exfoliation. Exfoliation deposits were identified with monoclonal antibodies (mAb) HNK-1 and NC-1 to the HNK-1 carbohydrate epitope, and with five lectins (Bauhinia purpurea agglutinin, Concanavalin A, Lens culinaris agglutinin, Phaseolus vulgaris erythroagglutinin, and Ricinus communis agglutinin I) using the avidin-biotinylated peroxidase complex (ABC) method. RESULTS: Marked exfoliation deposits in all involved eyes, and weak exfoliation deposits in one fellow eye were consistently detected in light microscopic, immunohistochemical, and lectin histochemical examinations. Similarly labeled deposits were present around a population of blood vessels of the iris in every involved and fellow eye. Particularly in fellow eyes, these subendothelial deposits were better visualized with mAbs to the HNK-1 epitope than they were with lectins. In the only fellow eye with early exfoliation, the reactivity around blood vessels was more conspicuous than the exfoliation deposits, whereas the reverse was true in the involved eyes. CONCLUSIONS: Clinically unilateral exfoliation is asymmetric, rather than truly monocular. The findings in fellow eyes suggest that iris blood vessels become abnormal early in the process, even before exfoliation deposits are histopathologically seen in the posterior chamber. Marked asymmetry in exfoliation indicates an influence of modulating local factors that may be internal or external to the eye, and that also may be functional in bilateral exfoliation.

Aged↗
PubMed1996

Resin modified glass ionomer cements. In vitro microleakage in direct class V and class II sandwich restorations.

Microleakage of conventional chemically cured and resin modified glass ionomer cements (GIC), a compomer and a composite resin was studied in vitro in direct class V and class II GIC/composite sandwich fillings. None of the restorative techniques investigated completely resisted microleakage at both the occlusal and gingival margins. The dentinal gingival margins exhibited the highest leakage pattern. The compomer and the resin modified GIC showed a better seal than the chemically cured GIC's. The use of a liner as separating agent between composite resin and GIC in the class II sandwich fillings did not improve the seal. The results suggest that the initial bond obtained immediately after light curing of the resin modified GIC's is stronger than that for chemically cured GIC's. The contradictory results of dye leakage studies reported in the literature are discussed and in vivo evaluations are suggested necessary to predict clinical performance.

Composite Resins↗