Increased amount of type III pN-collagen in AAA when compared with AOD.

OBJECTIVE: the extent of the processing of type III procollagen to type III collagen was determined in nine human abdominal aortic aneurysms (AAA), and compared with ten samples of aortoiliac occlusive disease (AOD). METHODS: the aminoterminal propeptide (PIIINP) and telopeptide (IIINTP) of type III procollagen and collagen, respectively, were immunologically measured in the soluble and insoluble fractions of the extracellular matrix. The assay for PIIINP in the insoluble matrix was further validated. RESULTS: the insoluble matrices of AAAs contained at least 12 times more incompletely processed type III pN-collagen than AOD specimens (0.74% and 0.061%, respectively). Also, the soluble extracts of AAAs tended to contain more non-processed type III pN-collagen than free, properly cleaved aminoterminal propeptide. CONCLUSIONS: the larger amount of type III pN-collagen suggests an alteration in the metabolism of type III collagen in AAAs. This may partially explain the decreased tensile strength of the aortic tissue.

Familial high serum PICP: high even in skin interstitial fluid, suppressible by topical corticosteroid treatment.

Circulating C-terminal propeptide of type I procollagen (PICP), mostly originating from bone, is mainly cleared by mannose receptors (MRs) in liver endothelial cells (LECs). We hypothesized that skin macrophage MRs could also play a role in local (in situ) clearance of PICP originating from skin type I procollagen synthesis. We tested this hypothesis in a male subject with a genetic systemic clearance defect, apparently due to an abnormality in MR function in LECs (or in PICP structure). Since skin macrophages may express the same MRs as LECs do, the genetic defect could affect them as well; hence, if elevated PICP concentrations even in skin interstitial fluid (IF) were found in our subject, it would suggest a role for local MR-mediated PICP clearance in skin. Since glucocorticoids (GCs) upregulate MRs in vitro, we measured the effect of topical GC on suction blister fluid (SBF)-PICP of the test person as compared with normal subjects. SBF-PICP was elevated in the case, which was consistent with the hypothesis. Furthermore, the GC-induced decrease was accentuated. The results suggest that skin macrophage MRs can have a role in skin PICP clearance in situ.

Aminoterminal propeptide of the alpha1-homotrimer variant of human type I procollagen (hotPINP) in malignant pleural effusion.

The aminoterminal propeptide (hotPINP) of type I homotrimer, a putative malignancy-associated type I collagen variant, was purified for the first time and a method was established for its detection in pleural fluid. Samples of 58 patients, with malignant or benign disease, were studied with specific immunoassays for the two propeptides of type-I procollagen (PICP and PINP) and with HPLC-DEAE chromatography to separate the two PINP variants. HotPINP was present in 64% of both benign and malignant pleural effusion fluids, with the exception of malignant mesotheliomas, none of which showed the presence of hotPINP. Also the PICP to PINP ratios were lower than normal in both benign and malignant samples (altogether in 69% of samples), although this deviation was greater in malignancy. These two phenomena were independent of each other. As synthesis of the alpha1-homotrimer-variant of type-I collagen seems to be relatively common during the formation of pleural effusion, it may be generally related to a fibroproliferative reaction in the pleural wall.

New PCR-based method for the Sp1 site polymorphism in the COL1A1 gene.

Polymorphism in the Sp1 binding site in the first intron of the COL1A1 gene has been related to increased risk of osteoporosis in several populations. To overcome the difficulties associated with the use of mismatch oligonucleotide primers in the original method for its detection, we developed a procedure involving PCR amplification of a 598-base pair sequence from the intron and its digestion with the restriction enzyme Van 91 I. The more frequent allele is recognized by the enzyme, whereas the reaction is abolished in the less frequent allele. Two convenience samples from the population in northern Finland, consisting altogether of 173 individuals, were studied. The overall frequencies were 0.864 for the G and 0.136 for the T allele, with a heterozygocity of 27.2%. The frequency of the T allele is towards the lower end of the range observed for other European populations.

Type I collagen turnover and cross-linking are increased in irradiated skin of breast cancer patients.

BACKGROUND AND PURPOSE: The effects of radiation therapy on the turnover and structure of type I collagen were studied in irradiated and contralateral skin of 18 breast cancer patients without clinically evident fibrosis. MATERIALS AND METHODS: The rates of on-going type I collagen synthesis and degradation were assessed by the aminoterminal propeptide of type I procollagen (PINP) and by two different assays (ICTP and SP4) for the carboxyterminal telopeptide of type I collagen in the soluble tissue extracts, respectively. Also, TIMP-1, TIMP-2 and the MMP-2/TIMP-2 complex were measured in the tissue extracts. Insoluble skin matrices, containing the cross-linked type I collagen fibres, were heat-denatured and digested with trypsin. Then, the variants of the carboxyterminal telopeptide of type I collagen were separated by high performance liquid chromatography (HPLC). The major histidinohydroxylysinonorleucine (HHL)-cross-linked variant was quantified by the SP4 assay, and the minor pyridinoline analogue (PA)-cross-linked telopeptide was quantified by the ICTP assay. RESULTS: Both the synthesis and degradation of type I collagen were increased (r=0.906; P<0.001) on the irradiated side, whereas the concentration of the MMP-2/TIMP-2 complex was decreased. In the insoluble tissue digests, the HHL-cross-linked telopeptides of type I collagen, also, when expressed/tissue hydroxyproline, were increased in the irradiated skin. TIMP-1, TIMP-2 or PA-cross-linked telopeptides of type I collagen showed no differences between the two sides. CONCLUSIONS: Radiotherapy induces a long-term increase in the turnover of type I collagen and leads to the accumulation of cross-linked type I collagen in skin.

Increased amount of type III pN-collagen in human abdominal aortic aneurysms: evidence for impaired type III collagen fibrillogenesis.

PURPOSE: This study aimed to characterize the distribution of structural domains of type I and III collagens in the wall of abdominal aortic aneurysms (AAAs), by the use of undilated atherosclerotic aortas (aortoiliac occlusive disease [AOD]) and healthy abdominal aortas as controls. METHODS: Immunohistochemical staining was applied with antibodies for the aminoterminal propeptides of type I (PINP) and type III (PIIINP) procollagens, which represent newly synthesized type I and III pN-collagens. In addition, an antibody against the aminoterminal telopeptide of type III collagen (IIINTP) was used as a means of detecting maturely cross-linked type III collagen fibrils. RESULTS: The newly synthesized type III procollagen detected by means of PIIINP staining was concentrated in the media in aneurysmal aortas, whereas type I pN-collagen was localized in the intima in both AAAs and AODs. The healthy aortas showed no immunoreactivity for either PIIINP or PINP. The cross-linked type III collagen, detected by means of IIINTP staining, stained transmurally in all study groups, but appeared more abundant in the media in AAAs. CONCLUSION: Our results strongly suggest that the metabolism of type III collagen is enhanced in AAAs. Intensive type III pN-collagen staining was present mainly in the media layer in AAAs, suggesting a role of type III collagen in aneurysm formation, whereas type I pN-collagen was present in the intima in both AAAs and AODs, suggesting that type I collagen synthesis is a fibroproliferative response related to the atherosclerotic process. The increased type III pN-collagen in AAAs may result in impaired fibril formation and, thus, in decreased tensile strength of aneurysmal tissue.

Decreased protein C activation is associated with abnormal collagen turnover in the intraalveolar space of patients with interstitial lung disease.

Activation of the coagulation system in the alveolar space plays an important role in the pathogenesis of interstitial lung disease (ILD) and pulmonary fibrosis. The protein C (PC) pathway is the main modulator of coagulation activation. This study evaluated whether dysfunction of the PC pathway is associated with increased collagen synthesis in the intraalveolar space of patients with ILD. This study comprised 22 patients with ILD; of these, five had idiopathic pulmonary fibrosis (IPF), nine had sarcoidosis-associated ILD, and eight had collagen vascular disease-associated ILD (CVD-ILD). Thrombin-antithrombin complex (TAT) was measured as a marker of coagulation activation. As markers of the PC pathway activity, the concentration of activated PC-PC inhibitor (APC-PCI) complex and the APC-PCI/PC ratio were measured and, as a marker of collagen synthesis, the concentration of aminoterminal propeptide of type III procollagen (PIIINP) was measured in bronchoalveolar lavage fluid (BALF) of ILD patients. TAT was significantly increased in BALF from ILD patients as compared to control subjects. The concentrations of PIIINP were significantly elevated in patients with ILD as compared to healthy subjects. In contrast, the concentration of APC-PCI and the values of APC-PCI/PC ratio were significantly decreased in BALF from patients with ILD. BALF concentration of PIIINP was significantly and inversely correlated with the concentration of APC-PCI and with the APC-PCI/PC ratio. These findings suggest that dysfunction of the protein C pathway may have important physiopathologic implications in the development of pulmonary fibrosis in ILD.

Type I and III collagens in human colon cancer and diverticulosis.

BACKGROUND: Collagens are major proteins in the extracellular matrix, providing tissues with tensile strength. They are also important for cell adhesion and the invasion of malignant tumours. METHODS: Thirty-nine samples of human colon (24 diverticulosis, 6 malignant tumours, 9 controls) were collected during elective surgery. Immunoassays for different domains of type I and III collagens and procollagens were used in soluble tissue extracts and trypsin digests of tissue samples. RESULTS: The contents of cross-linked type I and III collagen telopeptides and total collagen were similar in diverticulosis and healthy tissue, whereas in malignant tissue maturely cross-linked type III collagen was scarce. Furthermore, some of the cross-linked type I telopeptide antigens were exceptionally small in size, indicating that the cross-linking of type I collagen in collagen fibres is impaired in cancer. The rate of type I collagen synthesis was clearly increased in malignancy, but not significantly in diverticulosis. However, type III collagen synthesis was increased in diverticulosis, but not in malignancy. CONCLUSIONS: In colon malignancy, the collagen cross-linking process was aberrant and the synthesis of type I collagen increased. In diverticulosis, the synthesis of type III collagen was increased, suggesting only moderately increased metabolic activity.

Immunochemical characterization of assay for carboxyterminal telopeptide of human type I collagen: loss of antigenicity by treatment with cathepsin K.

The assay for the cross-linked carboxyterminal telopeptide of type I collagen (ICTP) has been shown to reflect increased type I collagen degradation in such pathological conditions as bone metastases and rheumatoid arthritis, but to be rather insensitive to the changes in physiological bone collagen turnover (e.g., induced by estrogen or bisphosphonate treatment). To determine the reasons for this discrepancy we localized the antigenic determinant recognized by the ICTP assay and studied the effects of two major osteoclastic proteinases, cathepsin K (EC 3.4.22.38) and matrix metalloproteinase-9 (MMP-9; gelatinase B; EC 3.4.24.35), on immunoreactivity. The antigenic determinant was shown to reside within the hydrophobic phenylalanine-rich regions of the carboxyterminal telopeptides of the two alpha1 chains of human type I collagen, situated between the triple helical domain and the lysine-derived trivalent cross-link. This conclusion was based on differences between the amino acid sequences and cross reactivities of the corresponding human and bovine antigens before and after proteolytic treatments with chymotrypsin. A trivalent cross-link is necessary for providing such a structure, because the divalently cross-linked and monomeric natural and synthetic peptides from the same region, but containing only one phenylalanine-rich sequence, showed poor immunoreaction. Recombinant human cathepsin K cleaved the trivalently cross-linked ICTP structure at two sites between the phenylalanine-rich region and the cross-link, destroying the reactivity with ICTP antibodies. On the contrary, the treatment of isolated ICTP by the matrix metalloproteinases MMP-9 (gelatinase B), MMP-1 (collagenase 1), or MMP-13 (collagenase 3) had no effect on the immunoreaction. Our results indicate that the increased circulating concentrations of ICTP found in several clinical situations are most likely produced by matrix metalloproteinases, whereas cathepsin K-mediated, osteoclastic bone resorption destroys ICTP antigenicity.

Serial determinations of aminoterminal propeptide of type III procollagen (PIIINP) and prognosis in ovarian cancer; comparison to CA125.

During malignant growth many changes take place in the metabolism of fibrillar type III collagens in the connective tissues. The aminoterminal propeptide of type III procollagen (PIIINP) has been found to be often elevated in ovarian cancer. In the present study the prognostic value of serum PIIINP concentration in epithelial ovarian cancer is evaluated in relation to serum CA125. Fifty-six women were enrolled in the study. Serial venous blood samples were taken preoperatively and 6, 9 and 12 months after operation for PIIINP and CA125 determinations. The results were correlated to the three-year survival. In Kaplan-Meier survival analysis the preoperative (P = 0.0422), 9-month (P = 0.0062) and 12-month (P = 0.0062) serum PIIINP concentration distinguished between the patients with good and poor prognosis while CA125 did so only at 9- (P = 0.0005) and 12-month (P < 0.0001) follow-up. In the multivariate analysis the independent predictors of prognosis were the preoperative PIIINP and 12-month CA125 concentrations. The percentage changes in serum PIIINP concentration did not differentiate the patients with good or poor prognosis at any time point, whereas the changes in CA125 concentration significantly divided the patients into two prognostic groups during the second half of the postoperative year. We found that PIIINP and CA125 are complementary to each other as predictors of prognosis in epithelial ovarian cancer as preoperative PIIINP was better than CA125 and 1-year CA125 better than PIIINP in this function.

Cross-linked telopeptides of type I and III collagens in malignant ovarian tumours in vivo.

Malignant tumours often induce a fibroproliferative response in the adjacent stroma, characterized by increased expression of type I and type III procollagens. In normal tissues, fibrillar collagens normally undergo extensive intermolecular cross-linking that provides tensile strength to the tissue. Here we set out to characterize collagen cross-linking in human ovarian carcinoma tissue in vivo. Biochemical and immunochemical methods were used for cross-linked telopeptides of type I and III collagens in samples of benign and malignant serous tumours. The locations and staining patterns of these proteins were visualized immunohistochemically. The contents of both total collagen and the cross-linked type I and type III collagens in the malignant samples were only about 20% of those in the benign tumours. The cross-linked telopeptide antigens derived from the collagens were smaller and more heterogeneous in size in the malignant than in the benign tumours, indicating a defective cross-linking process scarcely leading to the formation of mature cross-links in the collagen fibres in malignancy. Immunostaining revealed disorganized type I and type III collagen bundles in carcinomas. These findings suggest that the collagen cross-linking process is aberrant in malignant tumours, possibly resulting in increased susceptibility of tumour collagens for the proteolysis often associated with tumour invasion.

Characterization of type I collagen synthesis and maturation in uterine carcinosarcomas.

BACKGROUND: Epithelial malignancies often induce an enhanced expression of interstitial collagens in the fibroblasts within the tumor tissue and the surrounding non-neoplastic stroma. In uterine carcinosarcomas (malignant mixed müllerian tumors [MMMTs]) both the stroma and the epithelium are malignant. METHODS: In this investigation, both in situ hybridization and immunohistochemical staining were applied with two different antibodies that were capable of distinguishing between newly synthesized and mature, trivalently cross-linked Type I collagen to define Type I procollagen mRNA expression and the synthesis and maturation of the corresponding protein in MMMTs. RESULTS: In the better differentiated parts of these tumors, in which anticytokeratins stained only clearly carcinomatous cells, Type I procollagen mRNA expression was limited to stromal fibroblasts; mature Type I collagen bundles were abundant and regular. In poorly differentiated areas, in which anticytokeratins stained only a few individual cells, Type I procollagen mRNA was expressed peculiarly by three morphologically different cell types. In addition to benign mesenchymal cells, Type I procollagen mRNA was present in atypical epithelial and mesenchymal cells. In these tumors, the collagen bundles close to the malignant cells were comprised of newly synthesized Type I collagen, with only little evidence of the presence of mature, fully cross-linked collagen. CONCLUSIONS: These results strongly suggest that the undifferentiated cells of MMMTs are capable of producing their own stroma with irregularly arranged collagen bundles.

The extracellular matrix in skin tumor development-a morphological study.

The development of cancer involves epithelial-stromal interactions. Alterations in the synthesis and deposition of type I and III collagens are related to the tumor morphology. Skin carcinogenesis in experimental animals provides a reliable model for the development of neoplasia. Ultraviolet (UV) irradiation is the main etiological factor for epidermal dysplasia and malignant tumors in man, but also for dermal degeneration. Non-neoplastic dermal changes and skin tumors induced by ultraviolet irradiation and 7,12-dimethylbenz(a)anthracene were investigated in various mouse strains with different susceptibilities to tumor formation. UVB irradiation resulted in an increased immunoreactivity of collagens in the dermis, in comparison with 7,12-dimethylbenz(a)anthracene. Increased synthesis and deposition of type I and III collagens were found in the stroma adjacent to benign alterations. In well-differentiated squamous cell carcinomas, a similar induction of collagen synthesis and deposition was observed. The destruction of fibrillary structures was more pronounced during the decrease of differentiation from moderately to poorly differentiated squamous cell carcinomas. Anaplastic carcinomas with spindle cell morphology displayed a delicate meshwork of reticular fibers and collagen III, and abnormal expression of mRNA for collagens in some malignant cells with epithelial characteristics. The underlying stroma reacts to the development of epithelial tumors in a reproducible way, which is related to the carcinogenic agent involved.

The value of synovial fluid analysis in the assessment of knee joint destruction in arthritis in a three year follow up study.

OBJECTIVES: To assess the predictive significance of synovial fluid (SF) analysis for progressive radiological knee joint destruction in arthritis. METHODS: Altogether 55 patients with arthritis and knee joint effusion were included in the study. The diagnosis was rheumatoid arthritis (RA) for 44 of them, chronic seronegative spondylarthropathy for seven and juvenile rheumatoid arthritis for four. The mean age of the patients was 51.8 (SD 14.9, range 19-82) years, and the mean duration of disease 10.9 (SD 9.2, range 0.5-37) years. In addition to the routine laboratory tests, different markers of collagen synthesis and breakdown in serum and SF were assessed. The radiological grade of the knee joint was assessed by Larsen's method at the baseline and after a three year follow up. RESULTS: During the follow up, Larsen's grade deteriorated in 22 (40%) patients. These patients had a significantly higher median level of cross linked carboxyterminal telopeptide of type I collagen (ICTP) in SF at entry than those who had a stable index (p = 0.035). Serum ICTP did not have any predictive value for a specific joint. The median levels of total SF leucocytes (p = 0.012) and the subgroup of polymorphonuclear leucocytes (p = 0.018) were higher in the patients with a stable Larsen's index. However, the relation of SF leucocyte level to radiological progression could not be confirmed in the RA group. CONCLUSION: It is concluded that SF analysis may help in the identification of patients with inflammatory arthritis who are at risk for progressive destruction in a particular joint. A high total SF leucocyte level is not necessarily associated with a poor prognosis. Instead, a high SF ICTP level seems to reflect accelerated bone degradation.

Complete processing of type III collagen in atherosclerotic plaques.

The extent of processing of type III collagen is assessed, and the proportions of type I and III collagens are estimated in atherosclerotic plaques obtained from the carotid artery, common femoral artery, and aorta. The fraction of type III collagen that had retained its amino-terminal propeptide (pN-collagen) was 42% in the soluble extract but only 0.0081% in the insoluble residue. Taken together, only 0.011% of the type III collagen in whole plaques was in the form of type III pN-collagen. Together with the small amounts of the free propeptides of type I procollagen, this finding indicates a low rate of collagen turnover. The amounts of solubilized telopeptides of type I and III collagens were measured, after heat denaturation and trypsin digestion of the collagenous helix, by specific immunoassays for the corresponding trypsin-generated antigens. The mean proportion of type III collagen was 61% (95% confidence interval, 58% to 65%) in the carotid and femoral artery plaques and 56% (95% confidence interval, 44% to 68%) in the aortic specimens. The completely processed and cross-linked type III collagen seems to be the major collagen type in atherosclerotic plaques.

Type I collagen metabolites as tumor markers in patients with lung carcinoma.

BACKGROUND: Components of the extracellular matrix play a fundamental role in the process of tumor invasion. The objective of this study was to evaluate the value of Type I collagen metabolites as tumor markers in patients with lung carcinoma. METHODS: In this study, the serum concentrations of the cross-linked carboxyterminal telopeptide of Type I collagen (ICTP) and the aminoterminal propeptide of Type I collagen (PINP) were measured in 59 consecutive patients with lung carcinoma. The blood concentrations of neuron-specific enolase (NSE), carcinoembryogenic antigen (CEA), sialyl Le-1 antigen (SLX), squamous cell carcinoma antigen (SCC), and D-dimer were also evaluated. Data obtained on 18 age-matched healthy subjects and 12 age-matched patients with benign lung disease were available for comparison. RESULTS: The serum concentrations of PINP were significantly higher in patients with lung carcinoma than in age-matched controls. Prechemotherapy values of PINP and ICTP were significantly increased in patients who did not respond to chemotherapy compared with those who did respond. PINP and ICTP were significantly correlated with clinical stage, extent of bone metastasis, survival time, and D-dimer. PINP was also significantly correlated with tumor size. ICTP was significantly correlated with CEA, SLX, SCC, and NSE. PINP also tended to correlate with these tumor-associated glycoproteins. PINP had a better receiver operating characteristic curve than ICTP. The specificity of PINP (79%) for the diagnosis of bone metastasis was superior to that of ICTP (58%). CONCLUSIONS: The results of this study showed that, in addition to the important information that ICTP and PINP provide about the tumor cell-extracellular matrix interaction, they appear to be of great value as adjunct tools for the diagnosis of bone metastasis and as markers of the clinical response to therapy, clinical progression, and prognosis in lung carcinoma patients. However, more studies must be conducted to evaluate further the utility of these markers before their application in clinical practice.

Type I and III collagen metabolites as predictors of clinical outcome in epithelial ovarian cancer.

We evaluated the significance of biochemical tumor markers, ie, aminoterminal propeptide of type III procoliagen, trivalently cross-linked COOH-terminal telopeptide of type I collagen (ICTP), aminoterminal propeptide of type I procollagen, and CA 125 in the prediction of ovarian cancer outcome and compared them with several classical indicators of prognosis. The concentrations of biochemical markers were determined from the preoperative serum specimens of 55 patients with epithelial ovarian cancer. In the univariate analysis, all biochemical markers except PINP and all conventional prognostic indicators except histological subtype correlated significantly with survival. In the multivariate Cox analysis of biochemical markers, serum ICTP remained the only significant prognostic indicator of overall survival. Among all variables, clinical stage and ICTP were the only independent and significant determinants of prognosis. Because the content of trivalently cross-linked, mature type I collagen (the breakdown of which is detectable in the ICTP test) in malignant ovarian cancer tissue has been reported to be lower and that of bivalently cross-linked and non-cross-linked collagen has been reported to be higher than in benign tumors, the source of excess ICTP in the circulation of ovarian cancer patients is most likely the degradative damage of soft tissues surrounding the progressively growing malignant lesions. The serum ICTP concentration can thus be regarded as an indicator of the invasion of ovarian cancer. Such information is not available by conventional methods. Therefore, the ICTP test will improve the accuracy of predicting clinical outcome in this disease.

Preoperative high type I collagen degradation marker ICTP reflects advanced breast cancer.

Type I collagen synthesis (PINP, PICP) and degradation (ICTP) markers were analysed from preoperative serum samples of 138 women with breast cancer (BC), 94 women with benign breast disease (BBD) and 100 healthy controls to evaluate the levels of these markers and the stage of BC at the time of diagnosis. We also compared the clinical utility of these markers in detecting BC with CA15-3 and CEA. The mean value of ICTP was statistically significantly elevated in the BC group (p < 0.001), as compared with the control group, but the elevated values in BC group were due to stage IV disease. The sensitivity of ICTP in detecting BC was 0.23, which was equal with CA15-3(0.24) or CEA(0.23). The sensitivity of both PICP and PINP for diagnosing BC was poor, but a tendency to higher serum levels of PINP and low PICP/PINP ratio was detected in patients with advanced stage IV disease. These results indicate that high preoperative serum levels of ICTP are associated with advanced BC, but like CA15-3 and CEA, its clinical value in diagnosing purpose is poor.

Type I and type III procollagen propeptides in amniotic fluid of normal pregnancies and in a case of mild osteogenesis imperfecta.

BACKGROUND: The propeptides derived from type I and III procollagens, PICP, PINP and PIIINP, indicate the synthesis of the corresponding collagens. Their circulating concentrations reflect the growth velocity in infants and children METHODS: We measured these propeptides in 145 samples of amniotic fluid of normal pregnancy. In addition, we have analysed an amniotic fluid and serum sample from a mother with osteogenesis imperfecta, and later the infant's serum sample was also collected for procollagen propeptide analysis. RESULTS: High concentrations of propeptides, 100-1000 times higher than those in adult serum, were found in early second trimester, decreasing significantly towards term, reflecting the decreased foetal growth rate. Interestingly, the amino-terminal propeptide of type I procollagen, PINP, decreased more that the corresponding carboxy-terminal propeptide, PICP, although both are in principle derived from the same protein. At both stages of pregnancy, the discrepant ratio of PICP to PINP indicated a molar excess of PINP. Abnormally low concentrations of PICP and PINP with normal PIIINP concentrations measured in amniotic fluid and in the serum indicated decreased synthesis of type I procollagen in a foetus/infant with mild osteogenesis imperfecta. CONCLUSIONS: Our data show a decrease in collagen synthesis with the stage of pregnancy and lower values of type I procollagen propeptides in a case of OI.

The level of the collagen cross-link pyridinoline reflects the improvement of cutaneous lesions in one case of skin alveolar echinococcosis.

Cutaneous parasitic lesions, associated with a dense fibrous reaction, markedly improved under albendazole treatment in one case of supraumbilical skin localization of alveolar echinococcosis. Since collagen cross-linking increases during fibrogenesis and contributes to the stability of fibrotic lesions, we monitored the level of the cross-links pyridinoline and pentosidine in skin lesions from this patient to determine if they would reflect the changes occurring during treatment. We looked at the deposition of cross-linked type I collagen by immunohistochemistry and also measured the serum concentrations of pentosidine and of a fragment of type I collagen (ICTP), which contains a site of pyridinoline formation. Albendazole treatment did not affect either the collagen content of skin lesions or the serum concentrations of ICTP and pentosidine, but it led to a pronounced decrease in pyridinoline level concomitant with the disappearance, observed by immunohistochemistry, of extensively cross-linked fibrotic type I collagen. The follow-up of collagen cross-linking by pyridinoline in skin tissue thus appears to be useful in reflecting the improvement of fibrotic skin diseases during therapy.