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Biomedical subjects

J Uitto

Publications and source records attributed to J Uitto.

At least 415 records · Page 23Linked to original sources
PubMed1987

Laser modulation of human immune system: inhibition of lymphocyte proliferation by a gallium-arsenide laser at low energy.

Cultured human lymphocytes were subjected to irradiation with a gallium-arsenide laser at energy fluence varying from 2.17 to 651 mJ/cm2, and the cell proliferation was assessed by [3H]thymidine incorporation. Both mitogenic proliferation in response to phytohemagglutinin and spontaneous cell proliferation were markedly inhibited by the laser irradiation at energy fluence as low as 10.85 mJ/cm2. Similarly, the functional response of cells to antigen stimulation in a one-way mixed-lymphocyte reaction was also diminished as a result of laser irradiation. The results indicate that laser irradiation at low energy can interfere with immune system in vitro, and similar modulation could potentially occur in human subjects exposed to laser irradiation in vivo.

Dose-Response Relationship, Radiation↗
PubMed1987

Large vessel sealing with the argon laser.

This study compared the histology, biochemistry, and tensile strength of laser-welded and sutured canine venotomies, arteriotomies, and arteriovenous fistulas. Twelve animals had bilateral femoral vessels studied, with one repair (control) closed with interrupted 6-0 polypropylene sutures, and the contralateral repair (experimental) welded with the argon laser. Specimens were examined at weekly intervals from 1 to 4 weeks (four animals for each type of repair), and were evaluated histologically by hematoxylin and eosin, elastin, and trichrome stains; biochemically by the formation of [3H]hydroxyproline as an index of collagen synthesis; and mechanically by tensile strength determinations. At removal, all experimental closures were patent without hematomas, aneurysms, or luminal dilatation. Histologic and biochemical examination and tensile strength determinations suggest that laser welding may be an alternative to sutures for repair of large-diameter venotomies, arteriotomies, and arteriovenous fistulas, as healing is comparable to that seen with suture repairs up to 4 weeks postoperatively.

Animals↗
PubMed1987

Lipoid proteinosis: ultrastructural and biochemical studies.

Lipoid proteinosis, a rare autosomal recessive disease, is histologically characterized by deposition of hyalinlike material in the dermis. In this study the pathologic processes of lipoid proteinosis were evaluated by ultrastructural and biochemical analysis of skin and cultured fibroblasts from a patient with classic features of the disease. Transmission electron microscopy revealed the presence of hyalinlike material with a granular appearance interspersed between collagen fibers. Immediately surrounding the blood vessel walls, there was reduplication of basal laminae in an "onionskin" arrangement. The fibroblastic cells in the affected dermis contained peculiar cytoplasmic inclusions. Biochemical studies with the cultured fibroblasts showed that the total synthesis of extracellular matrix components, as detected by the synthesis of radioactive hydroxyproline or the incorporation of 35SO4(2-) and [3H]glucosamine into macromolecules, was not altered in lipoid proteinosis. However, the relative expression of type I and type III procollagen genes, as detected by molecular hybridizations with pro-alpha 1(I) and pro-alpha 1(III) procollagen complementary deoxyribonucleic acid probes, was markedly altered in cultured fibroblasts. Specifically, the type I procollagen messenger ribonucleic acid (mRNA) levels were significantly reduced, resulting in a decreased type I/III procollagen mRNA ratio. Furthermore, the replicative capacity of lipoid proteinosis fibroblasts, as detected by the incorporation of radioactive thymidine, was reduced. Thus the skin fibroblasts from lipoid proteinosis demonstrate ultrastructural changes, as well as alterations in their phenotypic characteristics, and these changes may have relevance to the pathologic processes of this systemic disease affecting the skin and other organs.

Adult↗
PubMed1987

Laser vascular welding--how does it work?

This study evaluated the histology and electron microscopy of four samples of 2 cm long venotomies and artery-vein anastomoses formed in canine femoral arteries and veins using the argon laser (0.5 W power, 1 800 J/cm2, 4 min exposure/1 cm length of anastomosis). Welds were continuously irrigated with saline during the procedure to limit maximal temperatures to 44.2 +/- 1.6 degrees C (mean +/- SD), and the specimens were removed immediately following fusion and preserved for examination. Histologic and electron microscopic examination of different areas of the welds revealed various mechanisms of fusion including a) apposition of denatured collagen and elastin in the media and adventitia; b) bonding of vein medial collagen and elastin to the internal elastic membrane of the artery; and c) fusion consisting of a coagulum of platelets and fibrin depending on the alignment and apposition of the vessel edges. This study demonstrates that vascular tissue fusion by the argon laser occurs by various mechanisms. Future experiments should delineate which types of seal produce the optimal strength at the time of fusion, and enhance long-term healing.

Animals↗
PubMed1987

Aortitis presenting as Buerger's disease.

Buerger's disease is frequently diagnosed in young smokers, based on clinical presentation rather than histologic criteria. This report describes a young male with idiopathic aortitis who had been managed for 10 years as Buerger's disease solely on the basis of clinical manifestations. This case emphasizes the need for establishing histopathologic, and perhaps biochemical, criteria to identify the underlying arteriopathy.

Adult↗
PubMed1987

Biostimulation of wound healing in vivo by a helium-neon laser.

Clinical observations have suggested that low-energy lasers might stimulate wound healing. To understand the mechanism of the biostimulation, we previously examined the effects of low-energy lasers on collagen production by human skin fibroblasts and reported an increase of collagen synthesis in vitro. To examine the effects of low-energy lasers in vivo, hairless mice were experimentally wounded, sutured, and subjected to laser irradiation by a helium-neon laser with a power output of 1.56 mW and an energy fluence of 1.22 Joules/cm2. Experimental wounds were subjected to laser treatment every other day for 2 months; control wounds remained untreated. Specimens from the wounds were then examined for histological findings, tensile strength, and total collagen content. Results demonstrated a considerable improvement in the tensile strength of the laser-irradiated wounds at 1 and 2 weeks. Furthermore, the total collagen content was significantly increased at 2 months when compared with control wounds. These results suggest a beneficial effect of the helium-neon laser on wound healing in vivo.

Animals↗
PubMed1987

Regulation of collagen gene expression in cutaneous diseases with dermal fibrosis: evidence for pretranslational control.

Dermal fibrosis, characterized by collagen accumulation, is the hallmark of several cutaneous diseases. To examine the mechanisms of collagen deposition in fibrotic skin diseases, fibroblast cultures were established from the skin of patients with progressive systemic sclerosis, morphea, scleredema, familial cutaneous collagenoma, connective tissue nevi of the collagen type, or keloids; these patients served as prototypes of fibrotic skin diseases with varying clinical features and potentially different etiologic factors. Collagen production was assayed by the synthesis of [3H]hydroxyproline, and types I and III procollagen messenger RNA (mRNA) levels were determined by dot blot hybridizations using human type I and type III procollagen-specific cDNA probes. The collagen production in fibroblast cultures from the fibrotic diseases was increased up to 6-fold over the controls, and a relatively good correlation between the collagen production and type I collagen mRNA levels was noted. The type I/III procollagen mRNA ratio in control fibroblast cultures was 5.9 +/- 1.6 (mean +/- SD). The corresponding ratio in keloid cell culture was markedly increased, while slightly decreased values were noted in the case of morphea and familial cutaneous collagenoma; the values in other cultures were within the normal range. The results suggest that procollagen production in fibroblast cultures derived from fibrotic skin diseases reflects elevated levels of the corresponding procollagen mRNA. The increased mRNA abundance, suggesting pretranslational control, may result from enhanced transcriptional activity of the corresponding gene or alternatively reflects increased stability of the mRNA molecule.

Collagen↗
PubMed1987

Inhibition of prolyl hydroxylation during collagen biosynthesis in human skin fibroblast cultures by ethyl 3,4-dihydroxybenzoate.

The enzymatically catalyzed formation of 4-hydroxyproline plays a key role in the intracellular biosynthesis of collagen, since a critical number of 4-hydroxyprolyl residues is required for synthesis and secretion of triple-helical procollagen molecules under physiologic conditions. The enzyme catalyzing the conversion of prolyl residues to 4-hydroxyproline, prolyl 4-hydroxylase, requires ferrous ion, alpha-ketoglutarate, and ascorbate for its activity. 3,4-Dihydroxybenzoic acid has been known to act as potent competitive inhibitor of purified prolyl 4-hydroxylase with respect to one or several of the cofactors or cosubstrates of the enzyme. 3,4-Dihydroxybenzoic acid, however, is a poor inhibitor of prolyl hydroxylation in intact cells, probably due to its polarity not allowing it to enter the cells. In this study, several hydrophobic modifications of 3,4-dihydroxybenzoic acid were tested in human skin fibroblast cultures for their efficacy to inhibit the synthesis of 4-hydroxyproline. The results indicated that the ethyl ester of 3,4-dihydroxybenzoic acid was an efficient inhibitor of prolyl hydroxylation in fibroblast cultures, with Ki of approximately 0.4 mM. Ethyl 3,4-dihydroxybenzoate had little, if any, effect on the hydroxylation of lysyl residues, and it did not affect total protein synthesis or DNA replication in these cells. To test the hypothesis that ethyl 3,4-dihydroxybenzoate might serve as a potential antifibrotic agent, its efficacy in inhibiting prolyl hydroxylation in scleroderma fibroblasts was also tested. The results indicated that the synthesis of 4-hydroxyproline in scleroderma cell cultures was similarly reduced by ethyl 3,4-dihydroxybenzoate. Thus, structural analogs of the cofactors or cosubstrates of prolyl 4-hydroxylase, such as ethyl 3,4-dihydroxybenzoate tested here or its further modifications, may serve as inhibitors of posttranslational hydroxylation of prolyl residues also in vivo. These compounds could potentially provide a novel means of reducing collagen deposition in tissues in fibrotic diseases, such as scleroderma.

Cells, Cultured↗
PubMed1987

Retinoid modulation of collagenase production by adherent human mononuclear cells in culture.

Previous observations have suggested that retinoids might be useful for the treatment of rheumatoid arthritis. In this study we examined the effects of various retinoids on collagenase production by adherent human peripheral blood mononuclear cells in culture. We have previously shown that these cells, consisting predominantly of monocyte-macrophages, actively synthesize and secrete collagenase upon stimulation with concanavalin A. The cells were incubated in serum free medium with all-trans-retinoic acid, 13-cis-retinoic acid, all-trans-retinal, or Ro 10-9359 (trimethylmethoxyphenyl retinoic acid ethyl ester) for up to 72 hours, and the collagenase activity was determined with [3H]proline labelled type I collagen as substrate. The incubation of mononuclear cells with all-trans-retinoic acid in the concentration range 10(-7)-10(-5) mol/l resulted in a dose dependent inhibition of the collagenase production. All-trans-retinal was also a potent inhibitor, whereas 13-cis-retinoic acid and Ro 10-9359 in a concentration of 10(-5) mol/l had a lesser effect. Control experiments indicated that the inhibition of collagenase production by all-trans-retinoic acid did not result from inhibition of total protein synthesis nor could it be explained by induction of an inhibitory molecule. These results indicate that retinoids with distinct structural features can inhibit collagenase production by monocyte-macrophages, and suggest a role for retinoids in the treatment of rheumatoid arthritis.

Cells, Cultured↗
PubMed1987

Doxorubicin-induced inhibition of prolyl hydroxylation during collagen biosynthesis in human skin fibroblast cultures. Relevance to imparied wound healing.

Previous clinical and experimental observations have indicated that wound healing is impaired as a result of treatment with doxorubicin, a chemotherapeutic agent. In this study, the effects of doxorubicin were examined in human skin fibroblast cultures with respect to collagen production and fibroblast proliferation. The results indicated that the synthesis of hydroxyproline as a marker of collagen production was markedly reduced, with an approximate concentration of inhibitor yielding 50% inhibition of 1 microM. This inhibition could be explained, in part, by generalized inhibition of total protein synthesis, but in addition, there was a significant inhibition of prolyl hydroxylation during collagen biosynthesis, as indicated by a reduction in the ratio of [3H]hydroxyproline/([3H]hydroxyproline + [3H]proline). The latter effect was shown to result from inhibition of prolyl hydroxylase by doxorubicin. As a consequence of reduced prolyl hydroxylation, the stability of newly synthesized procollagen triple helix was shown to be compromised. At the same time, doxorubicin significantly reduced fibroblast proliferation in vitro, as determined by [3H]thymidine incorporation. Thus, reduced collagen production and inhibition of fibroblast proliferation may explain the reduced wound healing in patients undergoing treatment with doxorubicin.

Cell Division↗
PubMed1987

Modulation of collagen metabolism in cultured human skin fibroblasts by dexamethasone: correlation with glucocorticoid receptor density.

Connective tissue metabolism was studied in detail in three human skin fibroblast lines, demonstrating low, medium, or high levels of glucocorticoid receptor densities. In the cell lines with low and medium receptor density, dexamethasone, in the range of 10(-5)-10(-9) M, had no effect on collagen production, using short incubation time periods and high (20%) fetal calf serum concentration, while in the cells with highest receptor density, a slight stimulation of collagen synthesis was noted in the concentration range 10(-6)-10(-9) M. In the presence of low concentration (0.5%) of serum, dexamethasone markedly inhibited collagen production. The production of collagenase, assayed by degradation of 3H-labelled type I collagen substrate with a brief trypsin activation of the enzyme, was reduced in a dose dependent manner in all 3 cell lines, the inhibition with 10(-5) dexamethasone being up to 56% of the control. Similarly, the activity of an elastase-like neutral protease was decreased in the presence of dexamethasone. Thus the results indicate that glucocorticoids may have profound effects on the degradation of connective tissue components, while the effects on collagen synthesis may be more variable depending on the environmental milieu.

Collagen↗
PubMed1987

Glucocorticoid receptors in cultured human skin fibroblasts: evidence for down-regulation of receptor by glucocorticoid hormone.

In the present study, we have determined the specific glucocorticoid receptors in cultured human skin fibroblasts with [3H]dexamethasone as the ligand. The whole-cell assay was employed for determination of glucocorticoid receptor densities and binding affinities in fibroblast cultures established either from 16 healthy control subjects, from 4 patients with active progressive systemic sclerosis (PSS), from 3 patients with keloids and 3 patients with diabetes mellitus. The receptor densities in PSS, keloid, diabetes and control fibroblasts were in the same range, the values being 6.3 +/- 4.9, 7.7 +/- 3.6, 5.3 +/- 1.3 and 7.9 +/- 6.2 fmol/micrograms DNA (mean +/- SD), respectively. In further studies, the cells were incubated with 10(-7) M dexamethasone for 4 or 9 days before the receptors were assayed. The specific binding of [3H]dexamethasone in steroid treated cultures was 62 and 13% of that observed in controls, suggesting down-regulation. In contrast, incubation of fibroblasts with 10(-5) M all-trans-retinoic acid did not alter the binding of [3H]dexamethasone, suggesting lack of pharmacologic interference at the receptor level.

Cells, Cultured↗
PubMed1987

Argon laser-welded arteriovenous anastomoses.

This study compared the healing of laser-welded and sutured canine femoral arteriovenous anastomoses. Arteriovenous fistulas 2 cm in length were created bilaterally in the femoral vessels of 10 dogs and were studied at 1 (n = 2), 2 (n = 2), 4 (n = 3), and 8 (n = 3) weeks. In each animal, one anastomosis (control) was closed with running 6-0 polypropylene sutures, and the contralateral anastomosis (experimental) was sealed with an argon laser (0.5 watt, 4 minutes of exposure, 1830 J/cm2/1 cm length of anastomosis). At removal all experimental anastomoses were patent without hematomas, aneurysms, or luminal narrowing. Histologic examination at 4 weeks revealed that laser-welded anastomoses had less inflammatory response and almost normal collagen and elastin reorientation. At 8 weeks sutured anastomoses had significant intimal hyperplasia whereas laser repairs had normal luminal architecture. Tensile strength and collagen production, measured by the synthesis of hydroxyproline and the steady-state levels of type I and type III procollagen messenger ribonucleic acids, at the anastomoses and in adjacent vein and artery specimens were similar in sutured and laser-welded repairs at 2, 4, and 8 weeks. We conclude that argon laser welding of anastomoses is an acceptable alternative to suture techniques, with the advantage of improved healing without foreign body response and possible diminished intimal hyperplasia at the anastomotic line.

Animals↗
PubMed1987

Heritable skin diseases with molecular defects in collagen or elastin.

The recent progress made in understanding the normal biology and biochemistry of the extracellular matrix of human skin has allowed us to identify several different levels at which errors could be introduced into the structure and metabolism of collagen or elastin, the two major fibrillar components of the dermis. Currently, several heritable cutaneous diseases are known to display distinct collagen or elastin abnormalities. This article reviews some of the heritable cutaneous diseases and highlights those entities in which definite information on molecular alterations in collagen or elastin is available.

Adult↗
PubMed1987

Paraproteinemia in patients with scleredema. Clinical findings and serum effects on skin fibroblasts in vitro.

Four patients with paraproteinemia and scleredema were studied. Histologic features included marked thickening and fibrosis of the dermis and subcutis. Variable amounts of mucin deposits were detected in the interfibrillar spaces. Serum from one patient significantly stimulated collagen production in normal skin fibroblast cultures, whereas serum from another patient stimulated collagen production in autologous cell cultures. Moreover, serum from one patient stimulated the [35S]sulfate incorporation into the fibroblasts. Circulating serum factors, possibly related to the paraprotein, may enhance the synthesis of extracellular macromolecules by dermal fibroblasts in these patients, thus providing a mechanism for dermal fibrosis.

Aged↗
PubMed1986

Demonstration of cellular retinoic acid binding protein (CRABP) in chick embryo tendon cells and effects of retinoids on collagen synthesis in tendon and sterna.

The binding of all-trans-retinoic acid (all-trans RA) to specific cytosol proteins and the effects of retinoids on procollagen synthesis were studied in chick-embryo tendon cells. For the receptor assay, tendon cytosols were incubated with [3H]all-trans-RA in the presence or absence of 100-fold excess of nonlabeled all-trans-RA up to 20 hr at +4 degrees and unbound retinoid was removed by charcoal-dextran treatment or by gel filtration chromatography. The results indicated that chick-embryo tendon cells contained cellular retinoic acid binding protein (CRABP). The binding of [3H]all-trans-RA could be displaced by 13-cis-retinoic acid, but not by retinol or etretinate. In contrast no CRABP could be found in cartilage cells isolated from sterna or in whole sterna. The treatment of tendon cytosol with proteases (pronase, trypsin, chymotrypsin) abolished the specific binding of [3H]all-trans-RA. Gel filtration studies on Sephadex G-100 indicated an apparent molecular weight of 14,500-15,000 daltons for the all-trans-retinoic acid binding protein. All-trans-RA markedly decreased procollagen synthesis in isolated chick-embryo tendon cells, the inhibition being concentration dependent; the decrease was about 58% of the control in the presence of 10(-5) M all-trans-RA. Similar decrease was noted with 13-cis-RA and etretinate, while retinol was less effective. In isolated cartilage cells the dose of 10(-5) M of all-trans-retinoic acid decreased drastically total protein and collagen synthesis. The mannosylation of procollagen, the conversion of procollagen to collagen and the size of procollagen chains were not significantly affected. The results of the present study indicate that CRABP is not expressed in sterna of chick-embryos, and in contrast high levels of CRABP could be found in tendons. However, retinoids modulated collagen synthesis in both tissues. Thus it is possible that retinoids can affect the metabolism of different collagen types also in clinical use.

Animals↗
PubMed1986

Demonstration of elevated type I and type III procollagen mRNA levels in cutaneous wounds treated with helium-neon laser. Proposed mechanism for enhanced wound healing.

To assess laser modulation of wound healing, full-thickness cutaneous wounds were produced in the backs of pigs, and subjected to treatment with helium-neon laser. For comparison, some wounds were treated with non-laser energy source (a tungsten light) or left untreated as controls. Type I and type III procollagen mRNA levels were determined in the wounds by molecular hybridization with cDNA probes. The results indicated that type I and type III mRNA levels were markedly increased at days 17 and 28 of the healing in wounds treated with He-Ne laser, when compared to control or tungsten light-treated wounds. The results suggest that helium-neon laser stimulates wound healing by enhancing procollagen gene expression. These observations may have relevance to previous clinical studies suggesting that helium-neon laser stimulates wound healing.

Animals↗