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Biomedical subjects

M Laato

Publications and source records attributed to M Laato.

At least 55 records · Page 3Linked to original sources
PubMed1998

The distribution of collagen types I, III, and IV in normal and malignant colorectal mucosa.

OBJECTIVE: To compare the distribution of interstitial collagens (type I and III) and basement membrane collagen (type IV) in cancerous and normal colon. DESIGN: Retrospective study. SETTING: University hospital, Finland. SUBJECTS: 13 patients with colorectal cancer of different stages and grades. MAIN OUTCOME MEASURES: Indirect immunofluorescence labelling for type I, III, and IV collagens of fresh frozen tissue samples, both normal and cancerous, cut into serial sections 6 microm thick. RESULTS: In normal mucosa, the epithelial basement membrane showed an intense immunoreaction for type IV collagen. Type I and III collagens were localised to the interstitial stroma underlying it. The membrane in cancer samples was characterised by discontinuities and thinning as estimated by immunolabelling for type IV collagen. Furthermore, immediately adjacent to the membrane type I and III collagen positivity was fragmented. The cancerous stroma showed a strong positive immunosignal for type I and III collagens. CONCLUSION: Both the epithelial basement membrane and the collagenous matrix immediately beneath it are degraded in malignant tissue. This may suggest the simultaneous activation of several degradative enzymes (as type I and III collagens are at least in part degraded by different enzymes from type IV collagen) or alterations in the expression of collagen subtypes in normal compared with malignant tissue.

Collagen↗
PubMed1998

Inhibin gene expression in a large cell calcifying Sertoli cell tumour and serum inhibin and activin levels.

Inhibin is a potential tumour suppressor gene product in the gonads. While inhibin gene products may have a role in tumourigenesis, serum inhibin levels can be used as a marker for ovarian tumours derived from granulosa cells. Tumours derived from Sertoli cells, testicular counterparts of granulosa cells, are rare. To assess whether inhibin could be used as a human Sertoli cell tumour marker, serum inhibin and activin levels and inhibin subunit mRNA expression in the testis were studied. Northern blot and in situ hybridization revealed abundant expression of inhibin alpha, beta A, and beta B subunit mRNAs in large cell calcifying Sertoli cell tumours found in a 12-year old boy with Carney complex. The tumours were multifocal and bilateral. Serum inhibin levels were clearly elevated at the time of the diagnosis, decreased by 50% after one of the testes was removed, and were low or undetectable after the second orchidectomy six weeks later. Activin was undetectable before the orchidectomies, while a low concentration of activin-A was measured after them. Follicle stimulating hormone (FSH) concentration increased from normal pubertal value to castration level as expected. Normal seminiferous tubules also showed inhibin subunit alpha and beta B mRNA expression, whereas inhibin beta A mRNA was expressed in normal Leydig cells. These data suggest that serum inhibin reflects Sertoli cell activity and can be used as a human tumour marker.

Activins↗
PubMed1997

The effects of interleukin-1 and prostaglandin E2 on accumulation of collagen and steady-state levels of pro alpha 1(I) collagen messenger RNA in experimental granulation tissue in rats.

The effects of human interleukin 1 beta (IL-1 beta) and prostaglandin E2 (PGE2) on experimental granulation tissue in rats and on granulation tissue cells in culture were studied. IL-1 beta and PGE2 were injected into subcutaneously implanted sponges during the first 3 days after implantation. The rate of collagen synthesis in fibroblasts was measured as synthesis of protein-bound 3H-hydroxyproline. The steady-state levels of pro alpha 1(I) and pro alpha 1(III) collagen chain mRNAs were estimated by Northern transfer analyses. By 7 days postoperatively IL-1 beta had decreased the hydroxyproline content of granulation tissue. PGE2 decreased non-significantly the amounts of hydroxyproline, but the steady-state levels of pro alpha 1(I) and pro alpha 1(III) collagen chain mRNAs were slightly elevated. In IL-1 beta-treated fibroblast cultures collagen production decreased by 15% and following PGE2 treatment by 34% compared with the controls. The latter effect could be abolished by indomethacin. Indomethacin alone stimulated collagen production by 40%. In vivo IL-1 decreases the formation of normal granulation tissue. This effect may be partly due to stimulation of secretion of PGE2.

Animals↗
PubMed1997

Effects of biodegradable self-reinforced polyglycolic acid, poly-DL-lactic acid and stainless-steel spiral stents on uroepithelium after Nd:YAG laser irradiation of the canine prostate.

OBJECTIVE: To evaluate the safety and tissue effects on canine uroepithelium and prostate of biodegradable self-reinforced polyglycolic acid (SR-PGA) and self-reinforced poly-DL-lactic acid (SR-PLA) spiral stents compared to stainless-steel (SS) spiral stents. MATERIAL AND METHODS: Twenty-five dogs (median body weight 12 kg) underwent a one-stage midline laparotomy and cystotomy. A side-firing Nd:YAG laser fibre was placed in the prostatic urethra antegradely and laser power applied at a setting of 20 W for 10 s in each side lobe, followed by dilatation to 4 mm diameter and insertion of a spiral stent. Dogs were randomized to receive an SR-PGA, SR-PLA or SS stent and no catheter was placed post-operatively. The dogs were killed after a follow-up of 1, 3 or 6 months and the bladder, prostate and urethra removed. Routine histological sections were prepared from the bladder, prostate, the proximal urethra immediately below the prostate and the distal urethra. RESULTS: Histological examination showed a mild to moderate foreign-body reaction and an acute inflammatory reaction after 1 month in the SR-PGA and the SR-PLA groups. The tissue effect was minimal in the SR-PGA group after 6 and 12 months. The SS stent group had more fibrosis, chronic inflammation and oedema at all follow-up assessments. There were erosions of the epithelium with subepithelial oedema in the animals with the SS stent. No dysplasia was detected and some remnants of the suture material were evident in the area of the cystotomy closure. There was one stricture at the apex of prostate in the SR-PGA group at 3 months in one re-operated dog. CONCLUSION: The histopathological changes in tissues caused by SR-PGA and SR-PLA stents were generally minor and decreased during the follow-up. The biocompatibility of SR-PGA and SR-PLA stents was good when combined with Nd:YAG laser treatment of the prostate.

Animals↗
PubMed1997

Clinical experience with the detubularized ileocecal reservoir and continent appendicoumbilical stoma in urinary diversion.

OBJECTIVE: To obtain clinical experience of a reservoir using a detubularized ileocecal segment (Mainz pouch) and continent appendiceal stoma connected to the umbilicus. METHODS: The operation was performed in 23 patients. The submucosally placed in situ appendix was connected to the umbilicus acting as the continence mechanism and route for self-catheterization. The follow-up period was 8-62 months. RESULTS: No operative mortality occurred. In 2 patients the postoperative period was complicated by catheter perforation of the appendix. In 4 patients stomal stenosis required excision of the stricture and reanastomosis. All patients are completely continent and catheterization is easy. CONCLUSION: Both functional and cosmetic results are very satisfactory.

Adolescent↗
PubMed1997

Are serum inflammatory markers age dependent in acute appendicitis?

BACKGROUND: Preoperative measurement of body inflammatory agents reduces unnecessary appendectomies by up to 30 percent. A decline in the formation of blood leukocytes and C-reactive protein with aging may hinder the correct diagnosis of appendicitis. STUDY DESIGN: White cell count and C-reactive protein were determined before appendectomy in 600 patients aged 0 to 5 years, 6 to 19 years, 20 to 39 years, 40 to 59 years, 60 to 79 years, and older than 80 years. Their records were analyzed. The sensitivity, specificity, diagnostic accuracy, and receiver-operating characteristic curves for C-reactive protein and white cell count to predict appendicitis were calculated separately for each age group. RESULTS: The rates of negative explorations and perforations were highest at both extremes of age. In uncomplicated appendicitis, the diagnostic potential of white cell count was better than C-reactive protein in all age groups except infants. The C-reactive protein was elevated similarly throughout human life, but only in those with perforated appendicitis. The receiver-operating characteristic curves confirmed that the performance of white cell count was better than C-reactive protein in the correct diagnosis in every age group except infants and octogenarians. CONCLUSIONS: The leukocyte response declines in 0- to 5-year-old children with appendicitis, but the C-reactive protein response is well preserved in all other age groups.

Adolescent↗
PubMed1997

Tumour necrosis factor-alpha selectivity modulates expression of collagen genes in rat granulation tissue.

OBJECTIVE: To study the effects of tumour necrosis factor-alpha (TNF-alpha) on granulation tissue in rats. DESIGN: Animal experiment. SETTING: University Hospital, Finland. MATERIAL: 48 rats in 6 groups. INTERVENTIONS: The test implants were treated with either a single or daily injections of 200 ng of TNF-alpha. The samples were collected 4 and/or 7 days postoperatively. MAIN OUTCOME MEASURES: Pro alpha 1 (I) and pro alpha 1 (III) collagen mRNA concentrations, hydroxyproline, nitrogen, uronic acids, and hexosamine content of the sponge; and ingrowth of new granulation tissue into the sponge. RESULTS: A single application of TNF-alpha resulted in no significant differences between the groups. After daily applications of TNF-alpha the accumulation of collagen hydroxyproline and volume of ingrowth of granulation tissue were significantly lower than in the controls. After 7 days there were significant reductions in the concentrations of RNA-ribose, nitrogen, and uronic acids. Daily injections of TNF-alpha reduced pro alpha 1 (I) collagen mRNA concentrations but those of pro alpha 1 (III) collagen mRNA levels were not lowered to the same extent. CONCLUSION: Repeated application of TNF-alpha was required to reduce the synthesis of collagen. This down-regulation was selective as pro alpha 1 (I) collagen mRNA concentrations were lowered more than those of pro alpha 1 (III) collagen mRNA.

Animals↗
PubMed1996

Suppression of syndecan-1 expression in endothelial cells by tumor necrosis factor-alpha.

Syndecan-1 is a cell surface proteoglycan that binds extracellular matrix components and modulates the activity of heparin-binding growth factors. The expression of syndecan-1 is modified during development, carcinogenesis, and tissue regeneration. During cutaneous wound healing, syndecan-1 expression is transiently induced in newly-formed capillaries of granulation tissue as well as in proliferating keratinocytes. To study the mechanisms underlying this regulation we investigated the effects of several growth factors/cytokines on syndecan-1 expression in two human cell lines: EA.hy 926 endothelial cells and HaCaT keratinocytes. None of these factors significantly altered syndecan-1 mRNA expression in cultured keratinocytes, but when given to endothelial cells, tumor necrosis factor-alpha (TNF-alpha) specifically and dose-dependently suppressed syndecan-1 expression at both mRNA and protein levels. TNF-alpha reduced the amount of syndecan-1 protein in EA.hy 926 cells in both the presence and absence of serum and, at the same time, induced the expression of intercellular adhesion molecule-1 (ICAM-1). The suppressive effect of TNF-alpha on endothelial syndecan-1 expression was reproducible in in vivo experiments in which TNF-alpha-coated beads were administered directly to healing skin wounds of mice. Data supporting these findings were further obtained by injecting TNF-alpha into an experimental rat granulation tissue model. In this tissue TNF-alpha suppressed syndecan-1 mRNA expression by approximately 80%. These results indicate that TNF-alpha is capable of down-regulating syndecan-1 expression in endothelial cells both in vitro and in vivo and suggest that similar mechanisms may be responsible for the changes in syndecan-1 expression observed during various regenerative, developmental, and malignant processes.

Animals↗
PubMed1996

Selective modulation of collagen gene expression by different isoforms of platelet-derived growth factor in experimental wound healing.

Subcutaneous sponges in rat were used as a wound model to study the changes in collagen gene expression induced by different isoforms of platelet-derived growth factor (PDGF). The steady state levels of proalpha1(I) and proalpha1(III) collagens rose markedly in response to PDGF-AB treatment. In marked contrast to PDGF-AB, PDGF-BB exerted a down-regulatory effect on the expression of type I and III procollagen mRNA levels. In situ hybridisation signal for proalpha1(I) collagen mRNA was most prominent in the periphery of the sponges in response to PDGF-AB. In PDGF-AA and PDGF-BB treated sponges, however, the hybridisation signal for proalpha1(I) collagen mRNA was evenly distributed. Immunolabellings demonstrated the presence of type I and III collagen epitopes and thus revealed the deposition of these proteins into developing granulation tissue. The volume of ingrown granulation tissue was estimated by measuring the cross-sectional area of the samples. PDGF-AB and PDGF-BB were both effective resulting in a significant increase in the amount of granulation tissue. However, only a limited enhancement of granulation tissue ingrowth was observed in response to PDGF-AA treatment. To conclude, PDGF-AB and PDGF-BB induced significantly the ingrowth of repair tissue in wounds. PDGF-AB distinctively upregulated collagen gene expression, while PDGF-BB primarily seemed to be mitogenic.

Animals↗
PubMed1996

A chance of misdiagnosis between acute appendicitis and renal colic.

The symptoms of right-sided renal colic mimic sometimes acute appendicitis. A prospective comparative study of 188 patients with ureteral stone and 188 patients with acute appendicitis was performed to evaluate the features of differential diagnosis. Appendicitis caused more often nausea (81 vs 11%), fever and localized pain in the McBurney (97 vs 59%) than renal colic. The patients with ureteral stone had tenderness in 16% in the right lower quadrant. The mean values of C-reactive protein (41 mg/l) and blood leukocytes (14 x 10(9)/l) were elevated in appendicitis, but not in renal colic (14 mg/l and 10 x 10(9)/ l). Urinanalysis revealed red cells in 92% of ureteral stones compared with 26% in appendicitis. Only one of 188 patients with appendicitis was first misdiagnosed to have renal colic. A mistake of appendicitis for ureteral stone is clinically rare occurring only once or twice per year in the hospital where 700-800 emergency appendectomies are annually performed.

Acute Disease↗
PubMed1996

Absence of bacterial DNA in the bladder of patients with interstitial cystitis.

PURPOSE: Although bacterial infection has been long considered a possible cause of interstitial cystitis (IC), no definitive proof for or against this hypothesis has been presented so far. We have used 16S rDNA bacterial polymerase chain reaction to study bladder biopsies and sterile urine samples from patients suffering from IC. This method is sensitive and detects all known eubacteria. MATERIALS AND METHODS: Bladder biopsies and sterile urine samples obtained by transabdominal puncture were studied from 11 patients with IC. As controls we studied 4 patients with other urological problems leading to partly similar symptoms and 5 healthy individuals. RESULTS: All samples from the IC patients were negative. One positive sample was obtained from a woman with a history of urinary tract infections who suffered from nonIC ulcerative cystitis. Her sterile urine sample yielded Lactobacillus acidophilus. CONCLUSION: These results indicate that an ongoing bacterial infection is not the cause of interstitial cystitis.

Cystitis, Interstitial↗
PubMed1995

Expression of acid cysteine proteinase inhibitor (ACPI) in the normal human prostate, benign prostatic hyperplasia and adenocarcinoma.

Acid cysteine proteinase inhibitor (ACPI or cystatin A) is a protein (12 kDa) which inhibits the action of several cysteine proteinases, e.g. cathepsins B, H, L and S. In this study the cellular location of ACPI has been immunohistochemically investigated in the normal human prostate, in benign prostatic hyperplasia (BPH) and in adenocarcinoma. ACPI was found in the basal epithelial cells of the normal prostate. The secretory epithelial cells did not express ACPI. In the hyperplastic prostate, the expression of ACPI was decreased and it was also expressed more focally in the basal cells. Hyperplastic basal cells also expressed ACPI. In prostatic adenocarcinoma, no ACPI expression was found. The absence of ACPI expression was obvious and if the sections contained both benign and malignant cells, only the benign glandular structures always expressed ACPI. The results suggest that expression of ACPI might be related to prostatic epithelial cell proliferation and differentiation. Possibly the detection of ACPI in tissue sections might be helpful in identifying prostatic adenocarcinoma, especially in cases with small carcinomatous foci.

Adenocarcinoma↗
PubMed1995

Platelet-derived growth factor isoforms PDGF-AA, -AB and -BB exert specific effects on collagen gene expression and mitotic activity of cultured human wound fibroblasts.

This study was designed to clarify the action of three different isoforms of PDGF (PDGF-AA, PDGF-AB and PDGF-BB) on the proliferation rate and collagen synthesis of fibroblasts cultured from normal human wounds. PDGF-AA and PDGF-BB down-regulated both the steady-state levels of pro alpha 1 (I) and pro alpha 1 (III) collagen chain mRNAs and the production of collagen, both in a dose-dependent manner. Interestingly, low concentrations (1 ng/ml) of PDGF-AB up-regulated the expression of type I and III procollagen mRNAs by cultured wound fibroblasts, while under high concentrations (30 ng/ml) of PDGF-AB this effect changed to the opposite. The proliferation rate of wound fibroblasts was stimulated by PDGF-BB which elicited a dose-dependent (1-30 ng/ml) stimulation of cell proliferation, whereas PDGF-AB and -AA were less effective in this respect.

Becaplermin↗
PubMed1995

Serum tumour necrosis factor compared with C-reactive protein in the early assessment of severity of acute pancreatitis.

Tumour necrosis factor (TNF) is an early mediator of sepsis and multiple organ failure; increased concentrations in serum are also observed in acute pancreatitis. In the present study the predictive value of TNF and C-reactive protein (CRP) concentrations on admission were compared in order to differentiate complicated cases of acute pancreatitis from the mild course in 77 patients. Serum TNF concentration exceeded the detectable level only in seven of 77 patients (9 per cent), although complicated pancreatitis developed in 18 (23 per cent). The sensitivity and overall accuracy of TNF concentration in predicting severe disease were only 16 and 74 per cent respectively. The corresponding values for CRP (concentrations greater than 100 mg/l) were 84 and 74 per cent respectively. These data suggest that, in contrast with CRP, the early determination of peripheral blood TNF concentration is of no clinical value in assessing the severity of acute pancreatitis.

Acute Disease↗
PubMed1995

A fibroblast cell line cultured from a hypertrophic scar displays selective downregulation of collagen gene expression: barely detectable messenger RNA levels of the pro alpha 1(III) chain of type III collagen.

The present study was designed to investigate the expression of type I, III and VI collagens by a fibroblast cell line initiated from a hypertrophic scar. The same tissue has previously been demonstrated to display markedly elevated expression of type I and III collagen mRNAs in vivo. Unexpectedly, slot-blot and Northern hybridizations revealed a barely detectable steady-state level of pro alpha 1(III) collagen chain mRNA in cultured hypertrophic scar fibroblasts. The levels of pro alpha 1(I) and alpha 2(VI) collagen chain mRNAs were essentially the same in fibroblasts cultured from hypertrophic scar and in fibroblasts cultured from normal skin. However, Northern blot analyses indicated that the ratio of 5.8 kb to 4.8 kb species of pro alpha 1(I) collagen mRNA was slightly reduced in fibroblasts originating from the hypertrophic scar compared to that in normal fibroblasts. When normal fibroblasts were incubated in conditioned medium from hypertrophic scar cultures, the expression of pro alpha 1(III) collagen chain mRNA decreased to a markedly lower level. Our studies suggest that collagen synthesis by fibroblasts in hypertrophic scars is stimulated by humoral factors which are active only in vivo. Furthermore, the results suggest that fibroblasts cultured from hypertrophic scar display a selective downregulation of different collagen genes and that this downregulation is exerted through an autocrine mechanism.

Adult↗
PubMed1994

Magnetization transfer imaging of lumbar disc degeneration. Correlation of relaxation parameters with biochemistry.

OBJECTIVES: The authors attempted to find out if magnetization transfer (MT) imaging with magnetic resonance imaging (MRI) provides new information of disc degeneration. SUMMARY OF BACKGROUND DATA: Magnetization transfer technique improves soft-tissue contrast and characterization. It measures the cross-relaxation and chemical exchange processes between free and macromolecule-bound water protons in tissues. METHODS: The lumbar MRI and MT of four living subjects and six cadaveric spines were performed at 0.1 T. Disc water, protein, proteoglycan, and collagen contents of cadaveric samples were correlated to MT parameters. RESULTS: The rate of magnetization transfer between free-water protons and the macromolecule-bound protons was elevated in degenerated discs. A positive correlation was found between disc collagen and total protein concentration and the rate of transfer. The contrast of normal and degenerated discs on MT images was not altered much. CONCLUSIONS: More studies are needed to fully establish the importance of MT processes in the disc.

Adult↗
PubMed1994

Normal and hypertrophic scars: quantification and localization of messenger RNAs for type I, III and VI collagens.

The expression of type I, III and VI collagens was studied in nine normal and two hypertrophic scars using slot-blot and in situ hybridization techniques. Slot-blot hybridization indicated that the steady-state levels of pro alpha 1(I) and pro alpha 1(III) collagen chain mRNAs were moderately elevated in two of the nine normal scars, whereas the two hypertrophic scars analysed displayed markedly elevated mRNA levels when compared with normal skin. The mRNA levels of alpha 2(VI) collagen chain were only slightly elevated in both types of scars studied. In situ hybridization was most informative when applied to hypertrophic scars. These lesions were characterized by the presence of intense hybridization signals for type I and III collagen mRNAs, and a moderate signal for type VI collagen mRNA, in nodules which were located in the upper dermis on each side of the original wound. This may explain, in part, why hypertrophic scars rise above the level of the surrounding skin. The results of the present study are in marked contrast to our previous findings on collagen gene expression in keloids and neurofibromas, in which the steady-state levels of type VI and I collagen mRNAs in particular were shown to be elevated. Thus, our results emphasize that distinct molecular mechanisms are operative in the development of clinically different dermal fibrotic conditions, such as normal and hypertrophic scars, keloids and neurofibromas.

Adolescent↗