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Biomedical subjects

M Laato

Publications and source records attributed to M Laato.

At least 37 records · Page 2Linked to original sources
PubMed2001

Leiomyoma of the urinary bladder.

We report a case of rare benign bladder leiomyoma. The patient was a 42-year old man complaining impotence. Digital rectal examination revealed a palpable pelvic tumor. Transurethral ultrasonography, computed tomography (CT), and magnetic resonance image (MRI) examinations all showed a cystic tumor measuring 10 x 8 cm. On the basis of these findings leiomyoma was suspected already before operation. The tumor was removed by open resection of bladder, and the diagnosis was confirmed by histology and positive immunohistochemistry.

Adult↗
PubMed2001

Interferon-gamma-induced inhibition of wound healing in vivo and in vitro.

This work was undertaken to study the effects of various doses of interferon-gamma (IFN-gamma) on developing granulation tissue in rats and on granulation tissue-derived fibroblasts in culture. For in vivo studies cylindrical hollow sponge implants were used as an inductive matrix for the growth of granulation tissue. In the test groups the implants were injected daily for four days with a solution containing 160, 800, 4000, or 20000 units of IFN-gamma while the implants of the control group were treated correspondingly with the carrier solution only. Analyses of granulation tissue in the sponge cylinders, carried out 7 days after implantation, showed an IFN-gamma-related decrease in the formation of new granulation tissue. The largest, dose-dependent effect was seen in the accumulation of collagen. For in vitro studies, cultures of rat granulation tissue fibroblasts were treated with 100, 500, 1000, or 5000 units/ml of IFN-gamma. IFN-gamma decreased collagen synthesis to about 50 per cent of that in controls. IFN-gamma treatment also decreased type I procollagen mRNA levels maximally by 41 per cent from the control level. It is concluded that IFN-gamma inhibits the formation of new granulation tissue by decreasing collagen synthesis.

Analysis of Variance↗
PubMed2001

The effects of sialic acid on the gene expression of fibrillar collagens: different changes in normal and fibrotic scar derived fibroblasts.

OBJECTIVE: To investigate the effect of free sialic acid on collagen gene expression in fibroblasts. DESIGN: Cell culture study. SETTING: University hospital, Finland. CELL LINES: Human granulation tissue fibroblasts, human hypertrophic scar fibroblasts and human keloid fibroblasts. INTERVENTIONS: Treatment of cell cultures with 3 microM, 30 microM and 300 microM N-acetyl-neuraminic acid. MAIN OUTCOME MEASURES: The measurement of steady state level of mRNA for type I and type III collagen. RESULTS: Fibroblast lines react dissimilarly under the influence of sialic acid. Granulation tissue fibroblasts showed decrease in the gene expression of type I and III collagen, while keloid fibroblasts contrastingly showed an increase. Hypertrophic scar derived fibroblasts showed no change. CONCLUSIONS: Sialic acids may decrease collagen gene expression in granulation tissue and that disturbed wound healing in diabetics and smokers may in part be due to direct effect of sialic acids on fibroblasts. Sialic acids may in part induce keloid formation.

Cells, Cultured↗
PubMed2001

Innervation of normal and hypertrophic human scars and experimental wounds in the rat.

The present study was designed to investigate the role of nerve elements in normal and aberrant human wounds, and in experimental rat wound healing model. The innervation of normal and hypertrophic human scars was studied using indirect immunofluorescence labeling with antibodies specific for neurofilament protein. Furthermore, in-growth of axons into experimental rat wounds was assayed. The results demonstrated that, in contrast to normal wounds, hypertrophic scars were traversed by a high number of bundles of axons. Our results also demonstrated that experimental rat granulation tissue which represented early phases of wound healing attracted axonal growth. To conclude, our findings indicate that normal wound healing is accompanied with innervation of the scars, and that hypertrophy of scars is accompanied with hypertrophy of nerves within the scars. Our results also suggest that aberrations in the innervation of scars may either cause aberrant wound healing, or neural hypertrophy may be a result of disturbed interplay in wound healing mechanisms.

Adult↗
PubMed2001

Burst abdomen. Local synthesis of nucleic acids, glycosaminoglycans, proteins and collagen in wounds.

BACKGROUND AND AIMS: Abdominal wound dehiscence and evisceration is a surgical emergency. The general phenomena leading to this complication are for the most part known. However, the local biochemical events of different layers of the abdominal wall in wound dehiscence have not been studied. The purpose of the present study was to analyze the synthesis and contents of DNA, RNA, proteins and collagen in fascial, subcutaneous and skin layers in burst abdomen. MATERIAL AND METHODS: The material consisted of 10 controls and 12 patients divided into two groups. Group A consisted of 7 patients with acute free or covered perforation of the gastrointestinal tract and group B consisted of 5 critically ill patients at admission. RESULTS: In group A, higher amounts of specific isotopes were accumulated into DNA, proteins and collagen in fascial and subcutaneous wound layers than in those of the controls. However, in critically ill patients the corresponding accumulation was lower than in controls. On the other hand, in both group A and B, the content of hydroxyproline (collagen) was below the control level in fascial and subcutaneous layers of the abdominal wound. CONCLUSIONS: The results indicate that the degradation of collagen exceeds the synthesis of collagen in wounds of patients with burst abdomen. Probably this increased degradation of collagen in wounds partly explains the higher wound disruption rate in these patients.

Abdomen, Acute↗
PubMed2001

Effects of glucose on collagen mRNA levels and collagen secretion in EAhy 926 endothelial cell line.

Diabetes mellitus (DM) is a complex metabolic disease associated with increased accumulation of extracellular matrix by endothelial cells and contributing to vascular complications of long-standing diabetes. On the other hand, DM is also associated with decreased accumulation of extracellular matrix in granulation tissue, which is suggested to be a consequence of impaired angiogenesis. The role of hyperglycemia in these situations is not fully understood. We examined the effects of high glucose concentrations on the gene expression and secretion of various collagens in cultured EAhy 926 endothelial cells. EAhy 926 endothelial cells expressed alpha1(I) collagen mRNA at a low level and small amount of the corresponding peptide was secreted from the cells; mRNA was not affected but peptide secretion was increased by elevated glucose concentration. mRNAs for type III and VI collagens were not detected in the endothelial cells. Furthermore, high glucose concentration in long term had no morphological effects on cultured endothelial cells but increased the expression of type IV collagen, which could rather be beneficial for angiogenesis in a healing wound. Our results suggest that high glucose concentration per se may contribute to increased accumulation of extracellular matrix in blood vessels but probably is not responsible for decreased angiogenesis and granulation tissue formation in diabetic patients.

Cell Line↗
PubMed2001

Surgically treated adenocarcinomas of the right side of the colon during a ten year period: a retrospective study.

BACKGROUND AND AIMS: Colon cancer is one of the most common malignancies in Finland. The purpose of the current study was to analyse the results of surgical treatment of right-sided colon cancers operated in the 1980s at Turku University Central Hospital. In addition, we compared the results to those reported from earlier decades. MATERIAL AND METHODS: One hundred and fifty-three patients with primary proximal colon cancer were operated in 1981-1990. The results were analysed retrospectively from patient records. RESULTS: The crude five-year survival rate of the patients was 48%. The most crucial factor affecting survival was the stage of spreading of the tumour. Obstructive tumours had a poorer prognosis than non-obstructive ones. CONCLUSIONS: The results of surgical treatment of proximal colon cancer were satisfactory at Turku University Central Hospital and slightly better compared to earlier reports.

Adenocarcinoma↗
PubMed2001

Leiomyoma of the urinary bladder.

We report a case of rare benign bladder leiomyoma. The patient was a 42-year old man complaining impotence. Digital rectal examination revealed a palpable pelvic tumor. Transurethral ultrasonography, computed tomography (CT), and magnetic resonance image (MRI) examinations all showed a cystic tumor measuring 10 x 8 cm. On the basis of these findings leiomyoma was suspected already before operation. The tumor was removed by open resection of bladder, and the diagnosis was confirmed by histology and positive immunohistochemistry.

Adult↗
PubMed2000

Expression of collagenase-3 (matrix metalloproteinase-13) in transitional-cell carcinoma of the urinary bladder.

Expression of collagenase-3 [matrix metalloproteinase-13 (MMP-13)] has been previously demonstrated in squamous-cell carcinomas of both the head and neck and the vulva, cutaneous basal-cell carcinomas, chondrosarcomas and melanomas. Using in situ hybridization, MMP-13 mRNA expression was detected in 13 of 23 (52%) urinary bladder transitional-cell carcinomas (TCCs). Expression was restricted to cells in the invading edges of tumors. No expression of MMP-13 mRNA could be detected in normal urothelium. As detected by immunohistochemistry, MMP-13 protein showed an expression pattern similar to that of MMP-13 mRNA. Expression of MMP-13 mRNA and protein was also detected in 2 bladder carcinoma cell lines (RT4 and T24). In these cell lines, TNF-alpha potently induced MMP-13 mRNA expression. Retinoids and a selective p38 inhibitor, SB203580, potently inhibited MMP-13 mRNA expression. Our results demonstrate MMP-13 expression in human urinary bladder carcinoma cells in vivo and in vitro and suggest that MMP-13 may serve as a marker for transformation and invasion in urinary bladder TCCs.

Adult↗
PubMed2000

New function for NF1 tumor suppressor.

The expression and subcellular localization of neurofibromatosis type 1 tumor suppressor was studied in keratinocytes induced to differentiate by increased Ca2+ concentration of the culture medium. Differentiating keratinocytes became intensely immunoreactive for neurofibromatosis type 1 protein, which was apparently associated with cellular fibrils. Double immunolabeling with antibodies to cytokeratin 14 and neurofibromatosis type 1 protein suggested an association of intermediate type cytoskeleton and neurofibromatosis type 1 protein. The presence of neurofibromatosis type 1 protein in cell preparations treated with cytoskeletal buffer indicated a high affinity interaction between intermediate filaments and neurofibromatosis type 1 protein. Further studies utilizing double immunolabelings revealed that the intense neurofibromatosis type 1 tumor suppressor signal on intermediate filaments was temporally limited to the period in keratinocyte differentiation in which the formation of desmosomes takes place. Keratinocytes were also cultured from nine patients with type 1 neurofibromatosis and were studied with respect to cell morphology, and association of neurofibromatosis type 1 protein with intermediate cytoskeleton. The results showed that keratinocytes cultured from patients with neurofibromatosis type 1 displayed a highly variable cell size and morphology compared to controls. The latter findings represent predicted alterations in a situation where cytoskeletal organization is disturbed. Furthermore, differentiating neurofibromatosis type 1 keratinocytes were characterized by a reduced number of cytokeratin bundles that were decorated neurofibromatosis type 1 protein. The results of this study suggest that neurofibromatosis type 1 tumor suppressor exerts its effects in part by controlling organization of cytoskeleton during the formation of cellular contacts.

Adult↗
PubMed2000

Sucrose has no beneficial effects on wound healing in rats.

OBJECTIVE: To evaluate the effects of sucrose treatment on the formation of granulation tissue in a standard wound model. DESIGN: Animal study. SETTING: University hospital, Finland. ANIMALS: 32 male Sprague-Dawley rats divided into 4 groups. INTERVENTIONS: Implantation of viscose cellulose sponge subcutaneously, and daily injection of three concentrations of sucrose (0.01, 0.1 or 1 M) or vehicle for 7 days. MAIN OUTCOME MEASURES: The amount of granulation tissue measured by chemical analysis and histology. The amount and distribution of types I and III collagen assayed by immunofluorescence. RESULTS: None of the three concentrations altered the amounts of DNA, RNA, hydroxyproline, nitrogen, hexosamines, and uronic acids in granulation tissue. Neither improvement nor deterioration was seen in the growth of granulation tissue in histological specimens. The amount and distribution of types I and III collagen was similar in controls and sucrose-treated rats. Type III collagen was most abundant near newly-formed vessels. Neither sucrose nor fructose was found in wound fluid while the concentration of glucose was significantly lower in all test groups than in controls. CONCLUSIONS: Sucrose solution had neither beneficial nor deleterious effects on the amount of developing granulation tissue in an experimental wound model. The amount and distribution of types I and III collagens were also not altered by sucrose treatment.

Animals↗
PubMed2000

Wound healing in denervated rat groin skin flap.

The purpose of the present study was to investigate the effect of denervation on dermal wound healing in rat groin skin flaps for 1-10 weeks. The structural differences between wounds in normal and in denervated skin were investigated histologically using Herovici's staining. Pro alpha1(I) collagen mRNA levels were studied using Northern hybridization. Denervation and reinnervation of the skin flaps was demonstrated with quantitative noradrenaline determination and immunohistochemically using neurofilament and S-100 antibodies. Denervation of the skin did not seem to have any apparent effects on wound healing as assessed by light microscopy. There were no significant differences in pro alpha1(I) collagen mRNA levels either. The thin muscle layer underlying the skin was the only element that clearly responded to the denervation.

Animals↗
PubMed1999

The cytostatic effect of 9-cis-retinoic acid, tretinoin, and isotretinoin on three different human bladder cancer cell lines in vitro.

Retinoids have been shown to have activity in both preclinical and clinical bladder cancer studies but their exact role in its treatment and prevention remains obscure. In this study cytostatic activity of a novel 9-cis-retinoic acid (9-cis-RA) was compared with two other retinoids: tretinoin and isotretinoin, in three different bladder cancer cell lines: RT4 (well differentiated), 5637 (moderately differentiated) and T24 (poorly differentiated). The three retinoids were incubated at concentrations of 0.3, 3 and 30 microg/ml with bladder cancer cells in microtitre plates for 3 and 6 days. The cytostatic effect was estimated by using luminometric measuring of ATP activity of viable cells in suspension. Compared with the older retinoids, tretinoin and isotretinoin, the highest concentration of 9-cis-RA had a cytostatic efficacy in all three bladder cancer cell lines tested. A clear dose response relationship was observed in isotretinoin-treated cultures after 6 days and in all 9-cis-RA-treated cultures. Tretinoin was either ineffective or had a stimulating effect on poorly differentiated tumour cells. To conclude, isotretinoin and 9-cis-RA had a cytostatic effect on human bladder cancer cells in vitro. However, the possibility of stimulating cancer growth at small doses, at least with tretinoin, and toxicity at high doses must be considered when planning clinical trials.

Alitretinoin↗
PubMed1999

Urinary bladder transitional cell carcinogenesis is associated with down-regulation of NF1 tumor suppressor gene in vivo and in vitro.

The NF1 gene product (neurofibromin) is known to act as a tumor suppressor protein by inactivating ras. The best documented factors involved in urinary bladder transitional cell carcinoma (TCC) are ras proto-oncogene activation and p53 suppressor gene mutations. This is the first study reporting alterations in NF1 gene expression in TCC. We examined NF1 gene expression in a total of 29 surgical urinary bladder TCC specimens representing grades 1 to 3 and in three cell lines, RT4, 5637, and T24 (representing grades 1 to 3, respectively). Decreased NF1 gene expression was observed in 23 of 29 (83%) TCC specimens as estimated by immunohistochemistry, the decrease being more pronounced in high-grade tumors. NF1 mRNA levels were markedly lower in TCC tissue compared with adjacent non-neoplastic urothelium, as studied by in situ hybridization for grade 3 TCC. Immunohistochemistry and Western blotting demonstrated that TCC cell lines expressed NF1 protein at different levels, expression being almost undetectable in T24 (grade 3) cells. Northern blotting for cell lines demonstrated reduced NF1 mRNA levels in grade 3 TCC cells. Reverse transcription polymerase chain reaction for cell lines and selected grade 2 and grade 3 tissue samples demonstrated NF1 type II mRNA isoform predominance in all samples studied. Our results show that both NF1 mRNA and protein levels are decreased in high-grade TCC, suggesting that alterations of NF1 gene expression may be involved in bladder TCC carcinogenesis.

Blotting, Western↗
PubMed1999

Effects of hexose sugars: glucose, fructose, galactose and mannose on wound healing in the rat.

The effects of four hexose sugars (D-glucose, D-fructose, D-galactose, D-mannose) on the developing granulation tissue in rats were examined. Cylindrical hollow sponge implants were used as an inductive matrix for the growth of granulation tissue. In the test group, the implants were injected with 0.1 ml of solution containing the different hexoses in 0.01, 0.1 and 1 M concentrations daily for 7 days while the implants of the control groups were injected with 0.1 ml of phosphate-buffered saline solution only. Analyses of granulation tissue and wound fluid in the sponge implants were carried out 7 days after implantation. The results demonstrated that galactose caused a significant increase in the accumulation of granulation tissue as estimated by histological analyses, but no significant differences were observed in various chemical analyses. In striking contrast, statistically significant decreases were observed in the number of leukocytes in wound fluid, in the amount of DNA, RNA, collagen hydroxyproline, nitrogen, hexosamines and uronic acids in sponges treated with 0.1 or 1 M mannose, reflecting decreased granulation tissue formation. This effect was also observed in histological analyses of the specimens. There were no major changes in sponges treated with glucose or fructose. In summary, the findings of the present study demonstrate that galactose may enhance wound healing and mannose treatment inhibits the inflammatory reaction in wound healing and decreases granulation tissue formation in an experimental wound model.

Animals↗
PubMed1999

Absence of integrin alpha1beta1 in the mouse causes loss of feedback regulation of collagen synthesis in normal and wounded dermis.

Integrin alpha1beta1 is a collagen receptor predominantly found in mesenchymal tissues. Mice lacking this receptor are viable. We have previously suggested that alpha1beta1 might participate in the down-regulation of collagen gene expression observed in cells suspended inside collagen gels. The results presented here demonstrate that integrin alpha1beta1 acts as a feedback regulator of collagen synthesis both in vitro and in vivo. Firstly, alpha1 null animals show a higher rate of collagen synthesis in the dermis in vivo. Secondly, fibroblasts derived from alpha1 null cutaneous wounds show a reduced sensitivity to collagen gel induced downregulation of collagen mRNA synthesis, as compared to their wild-type counterparts. An increase in collagenase synthesis is also seen in the alpha1 null dermis and in collagen gel suspended fibroblasts. While dermal thickness is normal in the alpha1 null animals, an increase is seen in skin thickness of alpha1 null but not alpha1 heterozygote animals on a background of collagenase resistant collagen. Increased expression of both collagen and collagenase mRNA are seen in experimental granulation tissue in alpha1 null animals, but their ultimate accumulation of collagen is normal, probably due to non alpha1 dependent paracrine regulators of collagen turnover.

Animals↗
PubMed1998

Upregulation of tumor suppressor protein neurofibromin in normal human wound healing and in vitro evidence for platelet derived growth factor (PDGF) and transforming growth factor-beta1 (TGF-beta1) elicited increase in neurofibromin mRNA steady-state levels in dermal fibroblasts.

We first studied expression of neurofibromin by immunohistochemistry in scars obtained from operations involving areas of healing wounds. The results demonstrated increased immunoreactivity for neurofibromin in the fibroblastic cell population of the lesions when compared with fibroblasts of apparently healthy perilesional skin, or those of intact control skin. Furthermore, dermal fibroblasts of 19 and 34 wk-old fetuses displayed a clearly detectable immunosignal for neurofibromin. In vitro studies were designed to investigate the potential effects of selected growth factors--known to be operative in wound healing--on neurofibromin mRNA steady-state levels in cultured fibroblasts. Northern transfer analyses revealed that different isoforms of platelet derived growth factor (PDGF) exerted selective effects on the neurofibromin mRNA levels: PDGF isoform AB elevated neurofibromin mRNA levels in a concentration-dependent manner when concentrations of 0.1, 1, 10, and 30 ng per ml were used. The maximal upregulatory effect of PDGF BB was reached at a concentration of 1 ng per ml. In contrast, PDGF AA did not alter the steady-state levels of neurofibromin mRNA. As estimated by RNase protection assay, transforming growth factor-beta1 (TGF-beta1) upregulated neurofibromin gene expression when concentrations of 0.5 and 5 ng per ml were used. Reverse transcription followed by polymerase chain reaction did not detect apparent alterations in the ratio of type I/type II neurofibromin isoforms in PDGF- or TGF-beta1-treated cultures. Taken together, our results suggest that expression of tumor suppressor protein neurofibromin is upregulated in response to skin injury, and that this upregulation can be mediated through PDGF and TGF-beta.

Adolescent↗