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Biomedical subjects

L Risteli

Publications and source records attributed to L Risteli.

At least 163 records · Page 9Linked to original sources
PubMed1989

Immunoelectron microscopic localization of laminin, type IV collagen, and type III pN-collagen in reticular fibers of human lymph nodes.

We studied the ultrastructural distribution of laminin, type IV collagen, and the amino terminal pro-peptide of type III collagen (type III pN-collagen) in normal human lymph nodes. After fixation with freshly prepared 4% paraformaldehyde mixed with 0.1% glutaraldehyde, cryoultramicrotomy proved to preserve the antigenicity of these proteins better than embedding in Lowicryl K4M. Sections were treated with rabbit antibodies against the 7S domain of human type IV collagen, the fragment P1 of human laminin, and the amino terminal pro-peptide of human type III pro-collagen, followed by anti-rabbit IgG conjugated to 10-nm colloidal gold. Laminin and type IV collagen were seen in the basement membrane structures of the blood vessels and in the walls of sinuses. The amorphous material between the collagenous fibers in locations corresponding to reticular fibers also contained laminin and type IV collagen. The amino terminal pro-peptide of type III pro-collagen was present in the collagenous fibers in reticular fibers and in the walls of blood vessels and sinuses. Therefore, a significant number of the type III collagen molecules in these fibers must have retained their amino terminal pro-peptide. These results indicate that the basement membrane proteins laminin and type IV collagen are genuine components of reticular fibers, as suggested earlier by immunohistochemical studies at the light microscopic level.

Basement Membrane↗
PubMed1988

Aminoterminal propeptide of type-III procollagen in serum--an indicator of clinical behavior of advanced ovarian carcinoma?

In ovarian carcinoma, elevated serum concentrations of the aminoterminal propeptide of type-III procollagen are related to the clinical stage of the disease and to the presence of ascites, which contains very high concentrations of the propeptide. In a follow-up of patients with advanced disease, favorable clinical course was associated with normalizing propeptide values, whereas in progressing disease the values increased several weeks before clinical progression. In stable disease the concentrations were constantly above the reference range. Laminin and type-IV-collagen-related serum antigens were mostly within the reference range.

Adult↗
PubMed1988

Differential expression of the laminin A and B chains in chimeric kidneys.

The expression of laminin in embryonic kidneys growing in ovo is followed with mouse-specific, affinity-purified antibodies against the laminin A and B chains. In mouse kidneys growing on the chicken chorioallantoic membrane, the epithelium and nephrogenic mesenchyme are derived from mouse and the vasculature from chicken chorioallantoic vessels. Hence, with the mouse-specific antibodies, it is possible to analyze the deposition of laminin chains by the nephrogenic tissue, because laminin derived from the chicken vasculature remains unstained. In these chimeras, only the laminin B chain, but not the A chain, is expressed in the undifferentiated nephrogenic mesenchyme. The basement membrane around the ureter bud is labeled by the antibodies against both laminin A and B chains. In the mesenchyme, the laminin A chain appears when the mesenchyme converts into tubules. The results suggest that the laminin A and B chains are synthesized differentially in the embryonic nephrogenic tissue.

Animals↗
PubMed1988

Serum basement membrane and type III procollagen-related antigens in primary biliary cirrhosis.

A characteristic histological lesion in early primary biliary cirrhosis (PBC) is disruption of the basement membrane around small bile ducts, which at later stages of the disease is followed by fibrosis. To assess the significance of serum basement membrane- and type III procollagen-related antigens in reflecting such processes, we have measured radioimmunologically the concentrations of serum laminin, type IV collagen and the aminoterminal propeptide of type III procollagen in 22 patients with PBC, classified into four stages according to liver histology. The mean laminin concentration in PBC patients was twice that of the healthy control subjects. Increased concentrations were observed in all patients with stage III or IV of the disease and also in 60% (6/10) of the patients, with early stages (I or II). Elevated serum type IV collagen concentrations were found only in four patients, all in the late, fibrotic stages of the disease. The basement membrane protein changes in serum were in accordance with immunohistochemical findings obtained with the antibodies against these proteins. Neither of these serum parameters emerged, however, as a significant predictive factor for survival. The changes in serum aminoterminal propeptide of type III procollagen resembled those in laminin P1. Moreover, the propeptide was also significant as a predictive factor for survival.

Adult↗
PubMed1988

Type IV collagen and laminin in slow and fast skeletal muscle in rats--effects of age and life-time endurance training.

The changes in the biochemical composition of basement membrane (BM) in slow-twitch (m. soleus, MS) and fast-twitch (m. rectus femoris, MRF) skeletal muscles of rats were studied during aging and life-time endurance training (treadmill running). The concentrations of the 7S domain of type IV collagen and of the P2 fragment of laminin were determined with radioimmunoassays in the muscles of rats aged 1, 2, 4, 10, and 24 months. The concentration of type IV collagen was higher in MS than in MRF and increased significantly with age. At older ages, the concentration tended to be higher in the MS of trained than untrained rats. The concentration of laminin was significantly higher in MRF than in MS, especially in old age. Consequently, the ratio of type IV collagen to laminin was significantly higher in MS than in MRF, the difference increasing with advancing age. The results show that the BMs in slow muscle are much more collagenous than those in fast muscle which contains, on the contrary, a higher concentration of laminin. This difference seems only partly to be explained by the higher capillarization of slow twitch muscle fibers. Aging and training seem further to distinguish the composition of the BM in slow and fast muscle.

Aging↗
PubMed1988

Laminin and type IV collagen in different histological stages of Kaposi's sarcoma and other vascular lesions of blood vessel or lymphatic vessel origin.

Immunohistochemical staining was used to demonstrate basement membrane (BM) laminin and type IV collagen in eight cases of Kaposi's sarcoma (KS). These KS were not associated with AIDS and represented different histological stages of the disease: patch (three cases), plaque (one case), and nodule (four cases). Nine cases of benign angiogenic lesions, five of blood vessel origin, and four of lymphatic vessel origin were also studied. An early event in vascular proliferation at the patch stage of KS was an intersection of dermal collagen bundles and the appearance of granular BM material around this space. With the increase of amount and linear arrangement of BM material, well-defined capillaries were formed. Two types of capillary were found in KS lesions. One showed morphological features of blood capillaries, with a round lumen; thick, continuous BM, and occasional pericytes in the wall. The other included irregularly shaped vessels with thin, often disrupted BMs; thus these capillaries morphologically resembled lymphatic capillaries. BM staining also clearly revealed the vascular nature of the nodular lesions of KS, which were composed of a network of slit-like spaces surrounded by BMs. The solid tumor cell areas were sparse; they were composed of spindle-shaped cells surrounded by thin, interrupted basal laminae. By using antibodies against human laminin and human type IV collagen, it was also possible to demonstrate thin, widely disrupted BMs subendothelially in normal dermal lymphatic capillaries. Typically, the BMs in lymphangiomas and lymphangiectasias were continuous and more clearly defined.

Aged↗
PubMed1988

Aminoterminal propeptide of type III procollagen in methotrexate-induced liver fibrosis and cirrhosis.

Twenty-four psoriatic patients on methotrexate were studied with liver biopsies and serum measurements of aminoterminal propeptide of type III procollagen (PIII NP). All but one of nine patients with serum levels of PIII NP above the normal range had liver fibrosis or cirrhosis and no normal liver biopsies were obtained in this group. In contrast, nine normal liver biopsies and two biopsies with minimal fibrosis were found among the 15 patients with normal serum levels of PIII NP. The study indicates that aminoterminal propeptide of type III procollagen can be utilized as a valuable non-invasive marker of fibrogenesis in the liver. This analysis is not specific for the liver, but it seems that the number of liver biopsies probably can be reduced in psoriatics on methotrexate who have normal levels of PIII NP.

Adult↗
PubMed1988

Serum aminoterminal propeptide of type III procollagen: a potential predictor of the response to growth hormone therapy.

The circulating concentrations of insulin-like growth factor I (IGF-I) and immunoreactive aminoterminal propeptide of type III procollagen (PIIINP) were measured in 12 children with short stature (8 GH deficient and 4 non-GH deficient) before and after 1 week, 5 weeks, and 3, 6, and 12 months of treatment with biosynthetic hGH. Seven children had a growth response (increase in relative growth velocity greater than 1.5 SD during the initial 6 months) to GH therapy (responders), whereas 5 failed to respond (nonresponders). No relationship was found between the pretreatment plasma IGF-I levels or their changes during therapy and the growth response. Serum PIIINP levels increased considerably in all but 3 children, after as little as 1 week of GH administration. After 5 weeks, all responders had an increase in their serum PIIINP concentrations of 40% or more, whereas the nonresponders had less or no increments. There was a close correlation between the GH-induced increase in serum PIIINP levels at 5 weeks and growth velocity after 6 months of GH therapy (r = 0.77; P less than 0.01). The correlation was even stronger with the growth velocity at 12 months (r = 0.83; P less than 0.001). The serum PIIINP response to short-term GH administration could be an early predictor of the growth response to long-term GH therapy. In contrast to plasma IGF-I, the PIIINP response may be useful both in GH deficient and non-GH deficient children.

Adolescent↗
PubMed1988

Cellular differentiation and expression of matrix genes in type 1 neurofibromatosis.

The cellular heterogeneity of cutaneous tumors from nine patients with type 1 (von Recklinghausen's) neurofibromatosis was studied using several antigenic markers with special reference to focal heterotopic differentiation and interindividual variation. Furthermore, cells which actively express the genes for type I and III collagens and fibronectin, the major components of the abundant extracellular matrix of neurofibromas, were localized using in situ hybridizations. In eight of nine cases, the S-100 protein positive cells, i.e. Schwann-like cells, composed 60 to 80% of the total cell population. However, in one case, only about 40% of the cells were S-100 protein positive. The latter tumor was studied with respect to perineurial cell differentiation and stained with a mixture of two antibodies, directed against the S-100 protein and type IV collagen. In Schwann cells, the staining reaction for S-100 protein was observed in the nuclear region, whereas the staining reaction for type IV collagen was located peripherally, corresponding to the basement membrane zone covering the cells. The stromal cells which showed only the peripheral staining profile were considered to be neoplastic perineurial cells. Distinct structures with epithelial, endothelial, or smooth muscle cell differentiation were present within the benign tumors, as detected by immunostaining for cytokeratin, epithelial membrane antigen, factor VIII-related antigen and desmin, respectively. In situ hybridizations revealed a clearly detectable expression of type I procollagen genes in less than 10% and type III procollagen gene in less than 5% of the total cell population. Active synthesis of fibronectin was limited to the vascular walls, when examined by in situ hybridization, and antibodies to cellular fibronectin localized to the same areas. However, antibodies to plasma fibronectin produced a uniform staining reaction throughout the tumors suggesting that most of the fibronectin in neurofibromas is plasma-derived. The latter observation suggests that neurofibroma cells are freely accessible to various plasma proteins, including growth factors, which may influence the growth characteristics of these lesions.

Antibodies, Monoclonal↗
PubMed1988

Rapid equilibrium radioimmunoassay for the amino-terminal propeptide of human type III procollagen.

This is an equilibrium-type radioimmunoassay for the amino-terminal propeptide of type III procollagen (PIIINP), which overcomes the problem of nonparallelism between the standard and human serum samples encountered with earlier assays. Proper selection of antiserum and reaction conditions diminishes interference from degradation products of the propeptide in serum. Because a rapid solid-phase-bound second-antibody step is included, the assay takes only 3 h. The intra-assay and the interassay CVs are both about 5%. In infants and children the concentration of PIIINP in serum closely parallels the growth-velocity curve. For 88 presumably healthy adults, the PIIINP concentration was 1.7-4.2 micrograms/L, about a third that measured with the previously available commercial assay. This is because of lack of inhibition by small Col 1 domain-related degradation products.

Adolescent↗
PubMed1987

The response evaluation of bone metastases in mammary carcinoma. The value of radiology, scintigraphy, and biochemical markers of bone metabolism.

The correlation between response of metastatic bone lysis and bone pain, various biochemical markers of bone metabolism, and radiological and scintigraphic findings was investigated in 49 women with breast cancer included in a calcitonin supportive therapy trial. All patients had dominant skeletal disease and were on stable systemic treatment (cytotoxic or hormonal) for a least 6 months before the first response evaluation. Bone pain correlated poorly with treatment response. Changes in sclerotic metastases did not show any apparent relation to changes in lytic lesions. A correlation between bone scans and lytic activity on radiographs was found. The absolute level of biochemical bone markers did not correlate with treatment response, but seemed instead to reflect the rate of bone turnover. The relative level of bone markers with respect to baseline showed better correlation to treatment response. The best conventional marker of disease activity was urinary hydroxyproline/creatinine. Propeptide of Type III procollagen (PIIINP), a novel marker reflecting collagen turnover, promises to be at least as sensitive as hydroxyproline. Stable and regressing patients had the same prognosis and significantly longer survival than progressors.

Biomarkers, Tumor↗
PubMed1987

Aminoterminal propeptide of type III procollagen in healing wound in humans.

For quantitative analysis of wound healing in surgical patients, samples of wound fluid were collected through a silicone rubber tube and their concentration of the aminoterminal propeptide of type III procollagen was measured with a specific radioimmunoassay. Peritoneal fluid, collected through an abdominal drain, and serum were also analyzed. At day 1 after operation, the mean concentration of the propeptide was 30 times higher than the mean preoperative serum level (2.5 micrograms/L). A significant increase (p less than 0.001) occurred at day 3 in the wound and at day 2 in peritoneal fluid. At day 5 the mean wound concentration (2670 micrograms/L) was 1000 times higher than the serum level. In serum a small but significant increase (p less than 0.05) was found at days 5 and 30. The increase in wound fluid resulted from the intact, liberated propeptide, indicating that the results reflect the synthesis of type III collagen deposited in the wound. This procedure offers a quantitative tool for wound healing studies. Other extracellular matrix components can also be measured, the sequential pattern of their appearance can thus be assessed, and disturbances and treatment effects in wound healing can be detected.

Adult↗
PubMed1987

Collagen metabolism in normal and complicated pregnancy: changes in the aminoterminal propeptide of type III procollagen in serum.

The turnover of type III collagen, a major constituent of the myometrium and the uterine cervix, during pregnancy was evaluated by monitoring serum antigens related to the aminoterminal propeptide of type III procollagen. Their concentration increased markedly towards term in most uncomplicated pregnancies, while their size distribution throughout the pregnancy resembled that seen in the sera of normal healthy persons. In some patients, however, the level remained low, indicating interindividual variation in the release into serum and metabolism of the propeptide. There were no distinct changes during or immediately after vaginal delivery. Values exceeding the reference range for uncomplicated pregnancies were found during weeks 28-37 in patients with pre-eclampsia, essential hypertension, intrahepatic cholestasis of pregnancy or twin pregnancy. Thus, pregnancy should be taken into account when evaluating results of the serum assay for the aminopropeptide and the use of this assay as an indicator of pregnancy complications warrants further study.

Cholestasis↗
PubMed1987

Serum aminoterminal type III procollagen peptide and the 7S domain of type IV collagen in patients with alcohol abuse. Relation to ultrastructural fibrosis in the acinar zone 3 and to serum hyaluronan.

Serum concentrations of the aminoterminal propeptide of type III procollagen and of the 7S domain of type IV collagen, presumed to reflect fibrotic activity in liver tissue, and of the glycosamonoglycan hyaluronan, were obtained from 40 alcohol abusers, at the time of liver biopsy. The serological results were related to morphological findings in liver tissue, i.e. no fibrosis, fibrosis without cirrhosis, micronodular cirrhosis and macronodular cirrhosis, and to ultrastructural indications of perisinusoidal fibrosis in the acinar zone 3. All patients with fibrosis and cirrhosis on light microscopy had elevated serum levels of the type III procollagen peptide as well as of the 7S domain of type IV collagen. However, due to a considerable overlap between the groups, no relations could be demonstrated to the severity of the fibrosis, supporting the assumption that these serological markers reflect the current fibrotic activity and not the amount of fibrotic tissue previously deposited. Among patients without fibrosis on light microscopy, a relation between the propeptide levels and ultrastructural perisinusoidal zone 3 fibrosis was observed, suggesting that type III procollagen peptide may be valuable in detecting very early liver fibrosis. A positive correlation was demonstrated between the serum concentrations of type III procollagen peptide and hyaluronan. As hyaluronan is degraded in the liver endothelial cells, it is suggested that the liver is involved, not only in the synthesis, but also in the degradation of the propeptide.

Adolescent↗
PubMed1986

Incorporation of sulphate into type III procollagen by cultured human fibroblasts. Identification of tyrosine O-sulphate.

Confluent cultures of normal human skin fibroblasts were labelled overnight with [35S]sulphate, and the incorporation of the isotope into type III procollagen, secreted into the medium, was verified by radioimmunoassay and immunoprecipitation after removing the heavily sulphated proteoglycans by anion-exchange chromatography. Type III procollagen and its pro and pN alpha chains were visualized in fluorographs of the immunoprecipitates. The labelled procollagen could be isolated by a combination of ion-exchange chromatography and gel filtration and was found to contain tyrosine O-sulphate, which was identified by thin-layer electrophoresis after Ba(OH)2 hydrolysis. The regions sulphated in the type III procollagen molecule were susceptible to pepsin digestion. Digestion with purified bacterial collagenase at +37 degrees C produced a labelled fragment that was recognized by antibodies against the aminoterminal propeptide of type III procollagen, indicating that the sulphated tyrosine residues are located either in this propeptide or in the non-helical telopeptide region of the type III collagen molecule proper. Sulphation of tyrosine residues is a new post-translational modification in procollagen, which could be involved in the regulation of the processing of type III procollagen into collagen and thus affect the formation of collagen fibres.

Cells, Cultured↗
PubMed1986

Serum markers for type IV collagen and type III procollagen in the myelofibrosis-osteomyelosclerosis syndrome and other chronic myeloproliferative disorders.

Myelofibrosis is characterized by excessive deposition of interstitial and basement membrane collagens in the bone marrow. In this study, specific radioimmunoassays for the aminoterminal propeptide of type III procollagen and for the 7S collagen domain of type IV (basement membrane) collagen were used to determine how this accumulation is reflected in serum. Of the 41 patients with chronic myeloproliferative disorders studied, the highest levels of both parameters were found in idiopathic myelofibrosis and in chronic myelogenous leukaemia associated with bone marrow fibrosis. Increasing degrees of bone marrow fibrosis were accompanied by increasing serum concentrations of both markers, except for osteomyelosclerosis, where notably low values were seen. Pathologically high values of one or both parameters were also found in a few patients with polycythaemia vera or a transitional myeloproliferative disorder. The antigens related to type III procollagen and type IV collagen correlated significantly with each other and with the leucocyte count. These parameters should provide noninvasive means for following the accumulation of interstitial and basement membrane collagens in the bone marrow.

Adult↗
PubMed1986

Fibrotic process and drug metabolism in alcoholic liver disease.

The effect of fibrosis on drug metabolism in alcoholic liver disease was evaluated in a comparison of the concentrations of serum aminoterminal propeptide of type III procollagen and basement membrane (BM; 7S domain of type IV collagen and laminin) antigens with in vitro (cytochrome P-450) and in vivo (antipyrine) drug metabolism in 67 alcoholics classified by liver histology. Alcoholics with intact or fatty liver had rapid or normal drug metabolism and normal collagen metabolism. Alcoholics with a fatty liver plus fibrosis or active cirrhosis had reduced drug metabolism and elevated levels of serum markers for collagen and BM metabolism. Alcoholics with inactive cirrhosis who had received therapy with enzyme inducers had a tendency toward normal drug and collagen metabolism parameters. Antipyrine metabolism, but not P-450 content, was related to the levels of serum type III collagen and BM markers. The fibrotic process, especially BM formation, creates a mechanical barrier that may prevent contact between blood and hepatocytes, thus delaying substrate availability.

Adult↗