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Biomedical subjects

J Uitto

Publications and source records attributed to J Uitto.

At least 433 records · Page 24Linked to original sources

Skin, joint, and pulmonary changes in type I diabetes mellitus.

Three hundred seventy-five patients with diabetes mellitus were examined for the presence of sclerodermalike skin changes, limited joint mobility, and vital capacity changes. Nineteen percent of patients had vital capacities 2 SDs below the mean of predicted values. There was no significant relationship between decreased vital capacities and duration of diabetes, sclerodermalike skin changes, limited joint mobility, smoking history, proteinuria, or retinopathy. Cutaneous involvement consisting of thickening, tightening, and/or a waxy quality of the skin was noted in 190 patients (51%). The severity of skin involvement correlated positively with the patients' duration of diabetes, age, severity of joint contractures, and diabetic retinopathy. Thus, sclerodermalike skin changes appear to reflect generalized connective tissue alterations in diabetes and may indicate increased risk for diabetic microvascular complications.

Adolescent↗

Laser welding of venotomies.

We investigated the histologic and biochemical effects of carbon dioxide and neodymium (Nd)-YAG laser welding on the healing of venotomies. Ten canine femoral venotomies 2 cm in length were approximated and welded with 10 600-nm wavelength, 1-W power over 20 to 25 s for CO2 laser, and 1060-nm wavelength, 1-W power over 30 to 40 s for Nd-YAG laser. On removal at one to three weeks, all veins (4/4 welded by CO2 and 6/6 by Nd-YAG) were patent without hematomas. Histologic and biochemical analyses of the venous tissues demonstrated active healing at the venotomy sites. We conclude that the CO2 and Nd-YAG lasers can be used successfully to weld venotomies and may provide an alternative to conventional suture techniques for repair of vascular lesions.

Animals↗

Comparison of laser-welded and sutured arteriotomies.

We compared the histologic features, tensile strength, and collagen synthesis of laser-welded and sutured arteriotomies. Four bilateral canine femoral or carotid arteries, 2 cm long, were studied at one through four weeks postoperatively, with one vessel (control) closed with interrupted 6-0 polypropylene sutures and the contralateral vessel (experimental) welded with an argon laser (0.5 W [1417 J/cm2], four-minute exposure per 1-cm length of incision). Histologic examination revealed that laser-welded arteriotomies had less inflammatory reaction, more normal collagen and elastin reorientation, and similar endothelial continuity when compared with the control, sutured wounds. The tensile strength of the one- and two-week laser-welded specimens was less than that of sutured wounds and became approximately equal to sutured repairs at three and four weeks. There were no significant differences in the rate of collagen synthesis. There was no evidence of abnormal healing in the laser-welded specimens, suggesting that argon laser welding may be an alternative to suture repair of arteriotomies.

Animals↗

Biological effects of laser welding on vascular healing.

The feasibility of welding thin-walled microvessels by laser has been established. This report summarizes our experience using laser welding to repair thick-walled, high-pressure, 4 to 8-mm canine arteries using CO2, Nd:YAG, and argon lasers. The CO2 laser did not produce seals that could withstand arterial pressure. Nd:YAG laser welds were initially successful, but the majority failed within 20 to 40 minutes. The argon laser uniformly sealed 2-cm-length arteriotomies that healed rapidly within 4 to 6 weeks and had less foreign body response compared to sutured controls. Laser welding may represent an alternative for repair of small- and large-diameter vessels with several advantages compared to conventional suture techniques.

Animals↗

Laser welding: an alternative method of venous repair.

This study compared the histology, biochemistry, tensile strength, and extensibility of Nd:YAG laser-welded and sutured venotomies. Two-centimeter-length bilateral canine femoral or jugular venotomies were evaluated with one vessel (control) closed with interrupted 6-0 polypropylene sutures, and the contralateral vessel (experimental) welded with the Nd:YAG laser (1 W power and 30- to 40-sec exposure). Specimens were removed and examined immediately after fashioning (t0) and at 1, 4, or 5 weeks post-operatively to compare the progression of healing. Histologic examination of the 4- and 5-week sutured wounds had granulomatous reaction around the sutures with areas of excessive collagen accumulation. In contrast, the laser-welded wounds had minimal inflammatory response, near normal collagen content, and minimal residual disorientation and break in the elastic fiber continuity. The rate of collagen synthesis in laser-welded wounds was approximately twice that of sutured wounds at 1, 4, and 5 weeks, and correlated with increased tensile strengths of lasered wounds. The extensibility of the 5-week specimens was 0.19 for sutured and 0.29 for laser-welded wounds as compared to 0.29 for normal vein. These preliminary data suggest that laser welding of venotomies may have several advantages over conventional suture techniques.

Animals↗

Skin closure by Nd:YAG laser welding.

Skin incisions 6 mm in length were made on the backs of hairless mice. Control wounds were closed with interrupted 5-0 Prolene sutures, and experimental wounds were approximated and closed by laser welding using a Nd:YAG laser. The wounds were examined daily, and specimens were excised at weekly intervals for histopathologic study, transmission electron microscopy, tensile strength determination, and type I collagen-specific messenger ribonucleic acid measurements. The laser-welded wounds demonstrated rapid healing. Histologic study showed a functional scar tissue at day 7 and a minimal residue of the original wound at day 14. Tensile strength of the control and experimental wounds was similar at all time points. The levels of collagen-specific messenger ribonucleic acid were significantly higher in the sutured group in comparison with the laser group or with normal control skin. This study suggests that laser welding might have advantages over suturing, since the former is sterile and nontactile, does not require introduction of foreign material into the wound, and provides subjectively improved cosmetic results.

Animals↗

Progressive nodular fibrosis of the skin: altered procollagen and collagenase expression by cultured fibroblasts.

A 33-year-old man presented with a spontaneous progressive cutaneous tumor-like fibrosis involving the right leg and buttock. Histologically the deep dermis was composed of numerous fibroblasts and dense bands of collagen, suggesting that the lesion might be related to an abnormality in collagen metabolism. Fibroblast cultures were established from the affected and normal-appearing skin. The growth rate of the lesional cells was essentially equal to that of control cells. The synthesis of procollagen was approximately 3.5-fold increased in the cells derived from the nodules when compared with control fibroblasts (p less than 0.001). The increase in procollagen synthesis was reflected by an approximate 6-fold increase in both type I and type III procollagen mRNA abundance in the lesional fibroblasts (p less than 0.001), thus suggesting an aberration in the pretranslational level of procollagen gene expression. In contrast, the synthesis of collagenase, the enzyme required for the initiation of collagen degradation, was decreased to approximately 25% of control values (p less than 0.0025), although the enzyme was catalytically normal. The data indicate that these cells are characterized by an increased synthesis of procollagen and decreased synthesis of collagenase, 2 phenotypic characteristics that could account pathophysiologically for the lesions. The unusual reciprocal nature of these biochemical parameters in 2 proteins important in connective tissue homeostasis suggests that this progressive tumor-like condition may have resulted from the expansion of a clonal population of cells.

Adult↗

Proteolytic enzymes in blister fluids from patients with dermatitis herpetiformis.

Proteolytic enzymes may be involved in blister formation in dermatitis herpetiformis (DH). We have examined collagenase, gelatinase and elastase-like enzyme activities in fluids collected from spontaneous blisters and from suction blisters raised on developing DH-lesions induced by application of potassium iodide. Control suction blisters were raised on unaffected DH-skin and on healthy volunteers. High enzyme activities were found in spontaneous blisters, and suction blister fluids obtained from developing lesions showed increased levels of gelatinase and elastase-like enzymes. Inhibitor studies revealed that a part of the elastase-like enzyme activity might be derived from inflammatory cells. Gel filtration chromatography disclosed two separate elastase-like enzymes which, as they had high molecular weights, could be either enzyme-inhibitor complexes or aggregates.

Blister↗

Collagenase production by human mononuclear cells in culture: inhibition by gold containing compounds and other antirheumatic agents.

Human peripheral blood mononuclear cells in adherent cultures have been shown to synthesise and secrete collagenase. In the present study we have examined the modulation of collagenase production in these cultures by several antirheumatic agents. Incubation of monocytes in serum free medium with sodium aurothiomalate in concentrations varying from 7.7 X 10(-7) to 7.7 X 10(-3) mol/l resulted in marked dose dependent inhibition of the collagenase production. This inhibition was apparently selective in that total protein synthesis or the viability of the cells were not affected. Similar inhibition of the collagenase production was also noted with auranofin, aurothioglucose, and chloroauric acid. The inhibition with auranofin was achieved with a concentration as low as 7.4 X 10(-8) mol/l. To examine the mechanisms of the inhibition of the collagenase activity induced by sodium aurothiomalate the production of prostaglandin E2 was also measured in the same cell cultures. Sodium aurothiomalate in concentrations greater than 7.7 X 10(-4) mol/l significantly inhibited the prostaglandin E2 production; the prostaglandin E2 production was not inhibited, however, in 7.7 X 10(-5) mol/l concentration, while the collagenase production was reduced by 51.0%. Also, exogenous prostaglandin E2 added to the cultures only slightly reversed the inhibition of the collagenase production by sodium aurothiomalate. Thus the inhibition of collagenase production by sodium aurothiomalate in human adherent mononuclear cell cultures appears to be independent of the inhibition of prostaglandin E2 production. The inhibition of collagenase produced by monocyte-macrophages, as shown here in vitro, may contribute to the clinical efficacy of the compounds tested in the treatment of rheumatoid arthritis.

Anti-Inflammatory Agents↗

UCLA conference. Biochemistry of collagen in diseases.

Collagen, the major extracellular matrix component, comprises a family of closely related, yet genetically distinct proteins that provide physiologic tensile properties to the tissues. The recent progress made in understanding the normal biochemistry and biology of collagens has permitted us to identify different levels at which errors might be introduced into the structure and metabolism of this protein. Several acquired and heritable diseases are now known to involve distinct abnormalities in collagen. This conference reviews some of the latest discoveries in the biochemistry of collagen and highlights some disease entities in which definitive information on molecular alterations in collagen is available.

Collagen↗

Characterization of elastase-like enzymes in various blistering diseases.

Blister fluid samples were collected from suction induced control blisters and from spontaneous blisters from various blistering diseases for the measurement of elastase-like enzyme activities using synthetic succinyl-L-(alanyl)3-paranitroanilide (SAPNA) and alanyl paranitroanilide (ala-PNA) as the substrates. The blister fluids derived from bullous pemphigoid, pyoderma or epidermolysis bullosa dystroficans lesions contained higher levels of elastase-like enzyme activities than burn blisters or fresh suction blisters. The gel filtration studies using Sepharose CL-4B chromatography revealed two major peaks of SAPNA hydrolysing enzyme activity in burn blister and in bullous pemphigoid blister. The first peak eluted in void volume, and the second peak had an apparent molecular weight of 2.5 X 10(5) daltons. The results indicate that various proteinases are present in blisters fluids and that they may participate in the blister formation by degrading structural components of the basement membrane zone and the dermis.

Aniline Compounds↗

Connective tissue biochemistry of the aging dermis. Age-related alterations in collagen and elastin.

Cutaneous aging represents a complex situation in which at least two independent factors--innate aging and solar exposure--contribute to the development of degenerative changes in the dermis. The biochemical and ultrastructural evidence reviewed in this article indicates that reduced collagen deposition, as a result of diminished collagen biosynthesis and reduced proliferative capacity of the fibroblasts, could explain the development of dermal atrophy and would relate to poor wound healing in the elderly. At the same time, perturbations in the supramolecular organization of the elastic fiber network lead to alterations in the mechanical properties of the skin, as manifested by loose and sagging skin with reduced resilience and elasticity.

Adult↗

Glucocorticoid action on connective tissue: from molecular mechanisms to clinical practice.

Glucocorticosteroids are highly effective in treating various acute and chronic diseases, but their long-term use is often accompanied by side effects, such as osteoporosis of skeleton and bones and atrophy of the skin. Clinically, many of these side effects involve changes in connective tissue. Glucocorticoid effects on connective tissue metabolism are, however, sometimes beneficial for instance, in the treatment of keloids or autoimmune connective tissue diseases. Recent advances in the biochemical technology have provided tools to examine the molecular mechanisms by which glucocorticoids affect connective tissue. These studies have shown distinct alterations in the extracellular matrix as a result of glucocorticoid treatment. This knowledge is useful for the further development of glucocorticosteroids with desirable action spectrum and with minimal side effects.

Animals↗

Differential effects of Nd-YAG laser on collagen and elastin production by chick embryo aortae in vitro. Relevance to laser angioplasty for removal of atherosclerotic plaques.

Aortae from 17-day old chick embryos were subjected to irradiation with a Nd:YAG laser at energy densities varying from 1.2 - 4.7 X 10(3) J/cm2. The aortae were pulse-labeled in vitro with [3H]proline or [14C]valine, and the synthesis of collagenous polypeptides and soluble elastin was examined by SDS-polyacrylamide gel electrophoresis, followed by fluorography and quantitative scanning densitometry. Irradiation of the aortae with Nd:YAG laser resulted in inhibition of the synthesis of the extracellular matrix proteins. The production of collagen was inhibited to a considerably larger degree than the production of elastin. Thus, the biosynthetic pathway for collagen production appears to be more susceptible to laser inhibition than the corresponding pathway for elastin production. These observations may have relevance to laser angioplasty which has been proposed to be applicable for removal of atherosclerotic plaques in human vessels. Specifically, the results suggest that inhibition of the extracellular matrix production may result in weakening of the vessel wall with subsequent aneurysm formation and rupture.

Animals↗