Serum Laminin Research Articles

Serum laminin is an independent prognostic factor in colorectal cancer

We investigated laminin, an important extracellular matrix component, to elucidate mechanisms of invasion and metastasis in colorectal cancer, and whether preoperative serum laminin is a predictive marker of high-risk groups. We measured preoperative serum laminin levels using a two-step sandwich enzymeimmunassay (EIA) method in 205 patients with colorectal cancer, 109 with colon cancer and 96 with rectal cancer, 52 with hepatic metastases, and 153 with no hepatic metastases. Mean serum laminin in patients with colon cancer was 606.3+/-260.2 ng/ml, significantly higher than that of 258.0+/-92.0 ng/ml in normal controls (P<0.0001). The positive rate was higher at 89.3% for laminin vs. 38.0% for carcinoembryonic antigen (CEA) and 19.5% for CA19-9. Mean serum laminin in patients with hepatic metastases was 668.0+/-274.7 ng/ml, significantly higher than that of 585.2+/-252.5 ng/ml in patients without hepatic metastases (P=0.0472). Survival rates were significantly lower in the high (> or = 520 ng/ml) than in the low laminin group (<350 ng/ml; P=0.0451). Univariate and multivariate analysis, using Cox's proportional hazard regression model, showed serum laminin is an independent prognostic factor in colorectal cancer, along with hepatic, pulmonary and peritoneal metastases. Preoperative serum laminin levels are a useful predictive marker of high-risk groups in colorectal cancer.

Serum markers detect the presence of liver fibrosis: A cohort study

Histologic examination of a liver biopsy specimen is regarded as the reference standard for detecting liver fibrosis. Biopsy can be painful and hazardous, and assessment is subjective and prone to sampling error. We developed a panel of sensitive automated immunoassays to detect matrix constituents and mediators of matrix remodeling in serum to evaluate their performance in the detection of liver fibrosis. In an international multicenter cohort study, serum levels of 9 surrogate markers of liver fibrosis were compared with fibrosis stage in liver biopsy specimens obtained from 1021 subjects with chronic liver disease. Discriminant analysis of a test set of samples was used to identify an algorithm combining age, hyaluronic acid, amino-terminal propeptide of type III collagen, and tissue inhibitor of matrix metalloproteinase 1 that was subsequently evaluated using a validation set of biopsy specimens and serum samples. The algorithm detected fibrosis (sensitivity, 90%) and accurately detected the absence of fibrosis (negative predictive value for significant fibrosis, 92%; area under the curve of a receiver operating characteristic plot, .804; standard error, .02; P < .0001; 95% confidence interval, .758-.851). Performance was excellent for alcoholic liver disease and nonalcoholic fatty liver disease. The algorithm performed equally well in comparison with each of the pathologists. In contrast, pathologists' agreement over histologic scores ranged from very good to moderate (kappa = .97-.46). Assessment of liver fibrosis with multiple serum markers used in combination is sensitive, specific, and reproducible, suggesting they may be used in conjunction with liver biopsy to assess a range of chronic liver diseases.

Serum laminin and collagen IV in inflammatory bowel disease

Background/Aims: Laminin and collagen IV have been proposed as extracellular matrix serum markers. Because fibrosis is a major complication of inflammatory bowel disease, serum concentrations of laminin and collagen IV...

Increased serum levels of laminin in the experimental cirrhosis induced by carbon tetrachloride

Serum laminin has been correlated with portal hypertension and sinusoid capillarization in chronic liver diseases. Little is known about its dynamics in liver diseases. To investigate the levels of serum laminin in experimental cirrhosis induced by carbon tetrachloride, as well as to correlate its level with the degree of hepatic fibrosis and portal hypertension. Forty-nine albino Wistar rats were studied. Twenty-three were treated with carbon tetrachloride solution at 8% and 16 were kept as controls. Between the 6th and 16th weeks, all animals were sacrificed, submitted to measurement of portal pressure and blood sampling of the femoral veins. Liver fragments were fixed for light microscopic studies. Hepatic fibrosis was classified as perivenular fibrosis, complete and incomplete septal fibrosis and cirrhosis. Determination of laminin concentration was performed by ELISA with an antibody against laminin isolated from Engelbreth-Holm-Swarm tumor. The portal pressure was correlated with the degree of hepatic fibrosis (rs = 0.82; n = 45). Its levels in septal fibrosis (10.8 +/- 1.2 cm H(2)0) and cirrhosis (13.6 +/- 3.1 cm H(2)0) were statistically higher when compared to control (7.9 +/- 1.5 cm H20) and perivenular fibrosis (9.1 +/- 0.8 cm H(2)0) groups. Peripheral blood laminin concentration in cirrhosis (40.0 +/- 18.7 mg/dL) was significantly higher when compared to control (13.8 +/- 12.1 mg/dL), perivenular fibrosis (19.1 +/- 15.5 mg/dL) and septal fibrosis (22.2 +/- 27.0 mg/dL) groups. The circulating laminin was correlated to the degree of hepatic fibrosis (rs = 0.59; n = 49) and to portal pressure (r = 0.29; n = 45). In the chronic carbon tetrachloride intoxication, laminin levels are better correlated with the development of hepatic fibrosis than with portal hypertension.

ZEOLITE AND POLYMER FILM BIO-CHEMICAL MEMS SENSORS

International Journal of Computational Engineering ScienceVol. 04, No. 02, pp. 239-242 (2003) BioMEMS and MicrofluidsNo AccessZEOLITE AND POLYMER FILM BIO-CHEMICAL MEMS SENSORSYIPING HUANG, JILIE KONG, JIA ZHOU, YINGCAI LONG, PO LI, HAIFEN XIE and MINHANG BAOYIPING HUANGDepartment of Microelectronics, 220 Handan Road, Shanghai, China, 200433, P. R. China Search for more papers by this author , JILIE KONGChemistry Department, Fudan University, 220 Handan Road, Shanghai, China, 200433, P. R. China Search for more papers by this author , JIA ZHOUDepartment of Microelectronics, 220 Handan Road, Shanghai, China, 200433, P. R. ChinaChina University of Science and Technology, Jinshan, 1000Xuefu Road, China, 201512, P. R. China Search for more papers by this author , YINGCAI LONGChemistry Department, Fudan University, 220 Handan Road, Shanghai, China, 200433, P. R. China Search for more papers by this author , PO LIDepartment of Microelectronics, 220 Handan Road, Shanghai, China, 200433, P. R. China Search for more papers by this author , HAIFEN XIEDepartment of Microelectronics, 220 Handan Road, Shanghai, China, 200433, P. R. ChinaChina University of Science and Technology, Jinshan, 1000Xuefu Road, China, 201512, P. R. China Search for more papers by this author and MINHANG BAODepartment of Microelectronics, 220 Handan Road, Shanghai, China, 200433, P. R. China Search for more papers by this author https://doi.org/10.1142/S1465876303000983Cited by:0 PreviousNext AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack CitationsRecommend to Library ShareShare onFacebookTwitterLinked InRedditEmail AbstractIn recent years, considerable interest has increased on the use of chemical and biomedical sensor arrays in conjunction with pattern recognition analysis for the identification of gases, liquid system or the determination of antigen-antibody interaction. Some sensor arrays technologies based on work carried out at Fudan University (China) are presented including (1) microcantilevers in resonating mode (2) polymer-based sensor arrays (3) capacitive immunosensor arrays.Keywords:sensor arraysmicrocantileverzeolitepolymer-based sensorgas sensorimmunosensor References H. P. Langet al., Analytica Chimica Acta 393, 59 (1999). Crossref, Google ScholarGuo-qing Guo and Ying-Cai Long, Separation and Purification Technology 24, 507 (2001). Crossref, Google ScholarY.-C. Long, H.-W. Jiang and H. Zeng, Langmuir 13, 4094 (1997). Crossref, Google ScholarE. Tsifrinaet al., Am. J. of Pathol. 155(5), 1625 (1999). Crossref, Google Scholar L. Castera, D. J. Hartmann, F. Chapel, C. Guettier, F. Mal, T. Lons and J. P. Richardet, Serum laminin and type IV collagen are accurate markers of histologically severe alcoholic hepatitis in patients with cirrhosis, J HEPATOL 32(3)(2000) 412-418 [1] H. P. Lang, M. K. Baller, et al, An artificial nose based on a micromechanical cantilever array, Analytica Chimica Acta 393 (1999) pp. 59-65 . Google Scholar FiguresReferencesRelatedDetails Recommended Vol. 04, No. 02 Metrics History Keywordssensor arraysmicrocantileverzeolitepolymer-based sensorgas sensorimmunosensorPDF download

A multicenter study to measure the validity of simple mucosal biopsy criteria predicting patients with ulcerative colitis ultimately requiring surgery

tests analysis of variance, student's t-test, Mann-Whitney U test and Linear regression were used Results: Mean serum laminin levels were 281.0+ 110.1 ng/ml in UC patients and 2756-+ 106.7 ng/ml in CD patients signihcantly higher compared to healthy controls (192.0-+ 178 ng/ml) and the inflammatory controls (198.5 -+ 32.5 ng/ml) (P<0.O001). Mean serum collagen IV levels were 72.8 -+ 22.9 ng/ml in UC patients 71.0 -+ 18.2 in CD patients significantly lower compared to healthy controls (79.8-+ 12.2 ng/ml) and the inflammatory contmls (889 +_ 246 ng/ml) (P<0.O001) A strong corrdation between serum laminin, but not of collagen IV, and disease activity was found in both diseases. Serum laminin was positively correlated with CRP (r=0.46, P=O.02) and negatively with albumin (r-0.54, p = 0.006). Conversely, no correlation between serum collagen IV and CRP or albumin was bund No significant association between laminin or collagen IV and disease localization or disease type was tound. [BD patients with primary sclerosing eholangitis (7 cases) had significant higher collagen IV (105.9 35.9 ng/ml) but not different laminin levels (283 9 + 133 5 ng,/mD compared to patients without primary sderosing chohngitis. Conclusions Serum levels of laminni are increased whereas serum levels of collagen IV are decreased ta patients with inflammatory bowel disease. They may be useful surrogate markers for sustained inflammation and tissue remodeling.

Serum laminin and collagen IV in patients with inflammatory bowel disease

Serum laminin and collagen IV in patients with inflammatory bowel disease

Detection of serum hyaluronic acid and laminin in patients with bladder tumors

In order to investigate the changes of serum hyaluronic acid (HA) and laminin (LN) levels and their clinical implication in the patients with bladder tumors, the serum HA and LN levels in 34 patients with bladder tumor and 30 cases of control group were detected by radioimmunoassay before and after operation. The results showed that the serum HA and LN levels in the patients with bladder tumors were significantly higher than those in control group (P<0.01) before operation, and decreased significantly after operation (P<0.05). The serum levels of HA and LN in infiltration tumors were higher than those in superficial tumors (P<0.05). The serum HA and LN levels in patients with lymph node metastasis were higher than those without lymph node metastasis (P<0.01). The investigation revealed that HA and LN might be involved in the malignant biology behavior of bladder tumors and could be used as important markers of assistant diagnosis and condition monitoring.

Clinical observation on effect of ruangan granule in treating chronic hepatitic liver fibrosis

To observe the clinical effect of Ruangan granule (RGG) in treating liver fibrosis.Methods: One hundred and twenty patients of chronic viral hepatitis B were randomly divided into two groups, 60 patients in the treated group and 60 patients in the control group. They were treated with RGG or composite Biejia Ruangan tablet ( ) respectively for three months. The changes of liver function, liver fibrosis indices, including fibronectin (FN), laminin (LN) and hyaluronic acid (HA), as well as liver morphology by B-ultrasonic examination were observed after treatment A three-month follow-up study was also conducted. In the treated group, the markedly effective rate was 50.0% and effective rate was 41.7%, while in the control group, the corresponding rates were 26.7% and 55.0% respectively. Comparison of the markedly effective rate between the two groups showed significant difference (P<0.01). The serum levels of FN, LN, HA as well as splenomegaly and portal vein widening in the treated group after treatment were significantly improved (P<0.05), as compared with those in the control group after treatment; significant difference was shown in comparison of serum FN, LN and HA. RGG could improve effectively serum liver fibrosis indices and liver function in patients of chronic hepatitic fibrosis. It is helpful in alleviating and inhibiting the genesis and development of liver fibrosis so as to block the progression of liver cirrhosis.

Detection of laminin in serum and ascites from patients with epithelial ovarian tumor.

The change in serum laminin (LN) level and its clinical significance in epithelial ovarian tumor were investigated. The LN levels in serum and ascites samples from 69 patients with epithelial ovarian tumor and 42 cases as control group before and after operation were analyzed by radioimmunoassay. The results showed that the serum LN levels in the patients with malignant tumors (157.85 +/- 14.37 ng/ml) were significantly higher than that in the control group (125.14 +/- 7.03 ng/ml) and in the patients with benign tumors (128.36 +/- 8.75 ng/ml) (both P < 0.01) before operation. The serum LN levels in the malignant group were decreased significantly after operation as compared with those before operation (P < 0.05). The serum LN levels in low-differentiated tumors was higher than those in moderate-differentiated tumors and high-differentiated tumors (P < 0.05). The LN levels in ascites (172.94 +/- 15.26 ng/ml) was significantly higher than in serum (161.34 +/- 6.59 ng/ml) (P < 0.05) in malignant tumors. The serum LN levels in the patients with lymph node metastasis (165.41 +/- 19.91 ng/ml) was obviously higher than those without lymph node metastasis (152.35 +/- 10.34 ng/ml) (P < 0.05). It was concluded that LN levels in serum and acistis were remarkably increased in malignant epithelial ovarian tumors, suggesting that LN might be one of important diameters reflecting tumor biological characteristics.

Comparison on efficacy between Astragalus-Polygonum Anti-Fibrosis decoction and Jinshuibao ("Equation missing" ) capsule in Treating liver fibrosis of chronic hepatitis B) capsule in Treating liver fibrosis of chronic hepatitis B

Objective: To observe the efficacy of Astragalus-Polygonum Anti-Fibrosis decoction (APAFD) and Jinshuibao capsule (JSBC) in treating liver fibrosis of chronic hepatitis B.Methods: Ninety-two cases of liver fibrosis of chronic hepatitis B were randomly divided into group A and group B. Patients in group A received APAFD for 48 weeks, and in group B, they received JSBC for 48 weeks. The effects on the level change of hyaluronic acid (HA), laminin (LN), pro-collagen III (PCIII) and collagen IV (CIV) as well as liver functional tests and liver biochemical parameters before and after treatment were observed.Results: Level of serum HA, LN, PCIII and CIV in group A declined more obviously than that of group B, the difference was significant (P < 0.01). The liver functional tests such as total bilirubin (TB), alanine aminotransferase (ALT), albumin/ globulin (A/G) ratio, hepatitis related serum biochemical parameters such as cholylglycine (CG), serum ferritin (SF), prealbumin (PC) of group A were all improved more significantly than that of group B (P < 0.01).Conclusion: APAFD is more effective than JSBC in treating liver fibrosis of chronic hepatitis B and in the inhibition of hepatic inflammation, hence it is a good composite Chinese herbal preparation against liver fibrosis.

Serum markers of lamellar basement membrane degradation and lamellar histopathological changes in horses affected with laminitis.

In order better to evaluate the extent to which degradation of the lamellar basement membrane (LBM) by matrix metalloproteinases (MMP) occurs in equine laminitis, we determined the concentration of type IV collagen and laminin in normal and laminitic horses, using specific immunoassays. Blood samples were obtained from both the jugular and the cephalic veins of horses (n = 10) before and after the induction of acute alimentary laminitis by carbohydrate overload. Jugular and cephalic venous blood samples were also obtained from horses affected with naturally occurring laminitis (n = 16) and nonlaminitic controls (n = 8). The serum collagen IV concentration was not changed following the induction of laminitis in the experimental group. Serum collagen IV concentration was increased in jugular venous blood obtained from cases of naturally occurring laminitis (mean +/- s.e. 218.04 +/- 18.59 ng/ml) compared with nonlaminitic controls (157.50 +/- 10.93 ng/ml) (P<0.05). Serum collagen IV concentration was also increased in jugular venous blood obtained from severely laminitic horses (219.50 +/- 18.18 ng/ml) compared with nonlaminitic controls (157.50 +/- 10.93 ng/ml) (P<0.05). A difference in serum concentration of collagen IV was not identified based on chronicity of naturally occurring laminitis. Serum laminin concentration did not differ between laminitic and nonlaminitic horses. Differences in serum laminin concentration were not identified based on sampling location (jugular or cephalic vein), severity of laminitic pain, or chronicity of spontaneous laminitis. In conclusion, the circulating concentration of collagen IV was increased in horses affected with naturally occurring laminitis. The potential role for serum collagen IV assay for characterisation of equine laminitis warrants further investigation.

Serum laminin and type IV collagen are accurate markers of histologically severe alcoholic hepatitis in patients with cirrhosis

Background/Aims: Severe alcoholic hepatitis occurs mainly in patients with cirrhosis, and has a high death rate. Corticosteroid therapy has been particularly advocated as reducing mortality in patients with severe histologic lesions. However, identification of these patients is difficult, requiring transvenous liver biopsy. Extracellular matrix serum markers have been proposed as non-invasive diagnostic tools in alcoholic liver disease. The aim of this study was to determine the accuracy of 5 extracellular matrix serum markers, i.e. laminin (Lam), N-terminal peptide of type III procollagen (PIIINP), type I (CI), type III (CIII) and type IV (CIV) collagens in identifying patients with severe histologic alcoholic hepatitis from among those with cirrhosis and suspected alcoholic hepatitis.Methods: We studied 80 consecutive patients with alcoholic cirrhosis and clinical suspicion of alcoholic hepatitis referred for transvenous liver biopsy. Clinical severity of alcoholic hepatitis was assessed according to Maddrey's score. Histological severity was scored using the sum of the 3 following items: polynuclear infiltration (0–3); hepatocytes alterations (0–3); Mallory bodies (0–2). According to this score, patients were divided into 3 groups: mild (1–3), moderate (4–6), and severe (7–8) alcoholic hepatitis. Serum levels of the 5 extracellular matrix serum markers were measured at the time of biopsy using radioimmunoassays. Diagnostic value for histologically severe alcoholic hepatitis of the 5 extracellular matrix serum markers was assessed using receiver operating characteristic curves.Results: Histological alcoholic hepatitis was present in 67 patients (mean alcoholic hepatitis score: 3.4±2.3). Maddrey's score was 66% sensitive and 69% specific for the diagnosis of severe histologic alcoholic hepatitis. The serum Lam and CIV concentrations were the most accurate in identifying correctly patients with severe histologic alcoholic hepatitis. At a cut-off of 4.1 UI/ml, Lam was 90% sensitive and 77% specific, whereas at a cut-off of 150 ng/ml, CIV was 89% sensitive and 77% specific. Combination of markers did not result in improved diagnostic value.Conclusion: In patients with cirrhosis, determination of serum Lam or CIV could represent a simple and accurate non-invasive method for identification of patients with histologically severe alcoholic hepatitis eligible for corticosteroid treatment.

Serum laminin as a marker of diabetic retinopathy development: a 4-year follow-up study

PURPOSE: The usefulness of laminin as a serum marker of diabetic retinopathy is a topic that generates conflicting views. The aim of the present study was to investigate the effect of diabetic retinopathy on serum laminin-P1, the larger pepsin resistant fragment of laminin, and to elucidate whether serum laminin-P1 could be an indicator of the risk for development of diabetic retinopathy. METHODS: In a prospective study, 97 consecutive diabetic patients (35 type 1 and 62 type 2) without diabetic retinopathy and a urinary albumin excretion rate lower than 20 μg per minute were enrolled in a 4-year follow-up study. Patients who developed microalbuminuria during the study were excluded in order to avoid the influence of diabetic nephropathy on serum laminin-P1. At the end of follow-up, data from ophthalmologic studies and serum laminin-P1 were evaluated in the 66 normoalbuminuric diabetic patients who completed the study. RESULTS: No statistical differences were observed in baseline laminin-P1 serum concentrations between patients who developed diabetic retinopathy (n = 15) and patients who remained without it during follow-up (n = 51). However, serum laminin-P1 levels obtained at the end of the study were significantly higher in patients who developed diabetic retinopathy (1.75 ± 0.33 U/ml versus 1.47 ± 0.27 U/ml; P = .002). Furthermore, statistical difference was observed when initial and final values of serum laminin-P1 were compared in patients who developed diabetic retinopathy (1.56 ± 0.27 U/ml versus 1.75 ± 0.33 U/ml; P = .001). Remarkably, an increase in serum laminin-P1 concentration was detected in all but two of the patients who developed diabetic retinopathy. The relative risk of development of diabetic retinopathy in patients who showed an increase in serum laminin-P1 during follow-up was 5.4 (95% confidence interval, 1.32 to 22.13). CONCLUSIONS: Serum laminin-P1 is a marker and a risk indicator of diabetic retinopathy but is not an early predictor of its development.

Basement membrane peptides as markers of liver disease in chronic hepatitis C

Background/Aim: Chronic hepatitis C is characterised by slow progression to liver fibrosis. In liver fibrosis, basement membrane components are increasingly deposited around the vessels and in the portal tracts. Serum assays can measure the two major components of the basement membrane, type IV collagen and laminin. The aim of this study was to determine whether serum levels of type IV collagen and laminin are related to severity of liver injury in chronic hepatitis C. Methods: Thirty-seven patients with chronic hepatitis C (CHC) and five healthy controls were studied. Serum type IV collagen was measured by a one-step sandwich EIA kit (Fuji, Japan) and serum laminin was measured by RIA (CIS, UK). Liver biopsies in patients with CHC were scored using a previously described grading and staging system. Liver biopsy scores were compared to serum levels of laminin, type IV collagen and alanine aminotransferase (ALT). Receiver operating characteristic (ROC) analysis was used to compare the ability of the assays to detect advanced liver injury. Results: The median serum concentration of type IV collagen was 127.1 ng/ml (range 17.7 to 317.4) in CHC patients compared to a median of 61.3 ng/ml (range 11.5 to 102.3) in controls, p=0.006. The median serum concentration of laminin was 1.12 U/ml (range 0.74 to 2.46) in CHC compared to a median of 0.87 U/ml (range 0.83 to 1.06) in controls, p=0.07. Both serum type IV collagen and laminin were significantly correlated with the fibrotic stage and also with the necroinflammatory injury scores - histological activity index, portal inflammation and periportal hepatitis. Serum ALT was significantly correlated with portal inflammation. Using ROC analysis, the area under the curve for type IV collagen and laminin was 0.83 ( p=0.001) and 0.82 ( p=0.0017), respectively, while the area under the curve for ALT was 0.54 ( p=0.1). Conclusions: Serum assays of basement membrane peptides are accurate non-invasive markers of liver fibrosis and liver inflammation in chronic hepatitis C. These markers are superior to serum ALT in reflecting liver injury and they have high specificity and sensitivity in detecting advanced liver disease in chronic hepatitis C.

Elevated serum type IV collagen: a sensitive indicator of the presence of cirrhosis in haemochromatosis

Background/Aim: Hereditary haemochromatosis can now be diagnosed by genetic testing, although determining the presence or absence of cirrhosis remains crucial to patient management. While many studies have investigated the utility of various serum markers of cirrhosis in chronic liver diseases, few have examined specifically patients with hereditary haemochromatosis. The aim of this study was to assess the utility of serum type IV collagen and serum laminin in diagnosing hepatic fibrosis and cirrhosis in patients with hereditary haemochromatosis. Methods: The study group consisted of 42 patients with hereditary haemochromatosis and 19 Caucasian controls. Serum type IV collagen, laminin, matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of metalloproteinase (TIMP-1) concentrations were measured by enzyme-linked immunosorbant assay in serum from patients with haemochromatosis and control subjects. Liver biopsies from patients with haemochromatosis were graded for fibrosis and correlated with serum markers of hepatic fibrosis. Results: Serum type IV collagen concentration was significantly increased in haemochromatosis patients compared to controls (130±79 ng/ml vs 81±17 ng/ml, p<0.05) and was significantly correlated with both the grade of histological fibrosis ( r=0.67, p<0.0001) and serum MMP-2 levels ( r=0.42, p<0.05). A serum type IV collagen concentration >115 ng/ml (mean+2 SD of controls) was 100% sensitive and 69% specific in detecting severe (grade 3) fibrosis and cirrhosis. The sensitivity results of serum laminin and TIMP-1 were 11% and 56 %, respectively. Conclusions: Elevated serum type IV collagen is a sensitive indicator of the presence of severe fibrosis and cirrhosis in patients with haemochromatosis. Useful markers of hepatic fibrosis in other chronic liver diseases may not be applicable to haemochromatosis.

Vitamin C Deficiency in Guinea Pigs Differentially Affects the Expression of Type IV Collagen, Laminin, and Elastin in Blood Vessels

Vitamin C deficiency causes morphologic changes in the endothelial and smooth muscle compartments of guinea pig blood vessels. Endothelial cells synthesize the basement membrane components, type IV collagen and laminin, and smooth muscle cells synthesize elastin in blood vessels. Therefore, we examined the possibility that vitamin C deficiency affects the expression of these proteins. Decreased expression of types I and II collagens in other tissues of vitamin C–deficient guinea pigs is associated with weight loss and the consequent induction of insulin-like growth factor binding proteins; thus we also used food deprivation to induce weight loss. Female guinea pigs received a vitamin C–free diet, supplemented orally with ascorbate. Vitamin C–deficient guinea pigs received the same diet but no ascorbate, and the food-deprived group received no food, but were supplemented with vitamin C. Concentrations of mRNAs for basement membrane components and elastin in blood vessels were measured by Northern blotting; overall basement membrane metabolism was assessed by measuring immunoreactive laminin and type IV 7S collagen in serum. Laminin mRNA in blood vessels and serum laminin concentrations were unaffected by vitamin C deficiency. Concentrations of type IV collagen and elastin mRNAs in blood vessels were not significantly affected in moderately scorbutic guinea pigs (0–7% weight loss), but with increased weight loss, type IV collagen mRNA was 57% (P < 0.05) and elastin mRNA was 3% (P < 0.01) of normal values. In food-deprived guinea pigs, type IV collagen mRNA was 51% (P < 0.05) and elastin mRNA was 35% (P < 0.05) of normal. Serum type IV 7S collagen concentrations were 25% of normal in scorbutic guinea pigs with extensive weight loss. The lower expression of type IV collagen and elastin mRNAs in blood vessels may contribute to defects observed in blood vessels during scurvy.

Basement membrane peptides as markers of liver disease in chronic hepatitis C

Abstract Background/Aim: Chronic hepatitis C is characterised by slow progression to liver fibrosis. In liver fibrosis, basement membrane components are increasingly deposited around the vessels and in the portal tracts. Serum assays can measure the two major components of the basement membrane, type IV collagen and laminin. The aim of this study was to determine whether serum levels of type IV collagen and laminin are related to severity of liver injury in chronic hepatitis C. Methods: Thirty-seven patients with chronic hepatitis C (CHC) and five healthy controls were studied. Serum type IV collagen was measured by a one-step sandwich EIA kit (Fuji, Japan) and serum laminin was measured by RIA (CIS, UK). Liver biopsies in patients with CHC were scored using a previously described grading and staging system. Liver biopsy scores were compared to serum levels of laminin, type IV collagen and alanine aminotransferase (ALT). Receiver operating characteristic (ROC) analysis was used to compare the ability of the assays to detect advanced liver injury. Results: The median serum concentration of type IV collagen was 127.1 ng/ml (range 17.7 to 317.4) in CHC patients compared to a median of 61.3 ng/ml (range 11.5 to 102.3) in controls, p =0.006. The median serum concentration of laminin was 1.12 U/ml (range 0.74 to 2.46) in CHC compared to a median of 0.87 U/ml (range 0.83 to 1.06) in controls, p =0.07. Both serum type IV collagen and laminin were significantly correlated with the fibrotic stage and also with the necroinflammatory injury scores - histological activity index, portal inflammation and periportal hepatitis. Serum ALT was significantly correlated with portal inflammation. Using ROC analysis, the area under the curve for type IV collagen and laminin was 0.83 ( p =0.001) and 0.82 ( p =0.0017), respectively, while the area under the curve for ALT was 0.54 ( p =0.1). Conclusions: Serum assays of basement membrane peptides are accurate non-invasive markers of liver fibrosis and liver inflammation in chronic hepatitis C. These markers are superior to serum ALT in reflecting liver injury and they have high specificity and sensitivity in detecting advanced liver disease in chronic hepatitis C.

Levels and molecular size distribution of serum laminin in adult type I diabetic patients with and without microangiopathy

the glycoprotein laminin, a cross-shaped complex of three genetically different polypeptide chains, is a structural component of the capillary basement membrane. Serum laminin concentrations of healthy controls (n = 60) and adult type I diabetic patients (n = 170) were not age-dependent. Laminin was correlated with hemoglobin A 1 (HbA 1) values in normooalbuminuric patients ( r S = .33, P < .0005, n = 116). Type I diabetic patients without nephropathy or retinopathy in good metabolic control had normal laminin levels. However, increasing stages of microangiopathy were associated with higher laminin levels. The molecular size distribution of serum laminin of control subjects (n = 4) and type I diabetic patients (n = 15) was analyzed by molecular-sieve chromatography. Laminin was eluted in two peaks with a molecular mass of 900 and 300 kd, most likely representing intact laminin and its P1 fragment, respectively. The areas of the two peaks were determined by two—gaussian function fitting. In patients without microangiopathy in poor metabolic control, an increase in the high—molecular weight (HMW) fraction could be detected as compared with healthy subjects and patients with acceptable metabolic control. Furthermore, the HMW laminin fraction and the ratio between the areas of the first and second peak increased with the stage of nephropathy ( P < .001, Jonckheere-Terpstra test). These results provide evidence that (1) laminin concentration is increased in chronic hyperglycemia, (2) laminin may be a marker of microangiopathic lesions, and (3) elevated laminin levels may reflect an increased synthesis and/or a defective incorporation of laminin into the capillary basement membrane.

Increased laminin-1 expression in hydatidiform mole.

To investigate the aetiology of hydatidiform mole, laminin-1 expression was determined in human villous tissues obtained from normal pregnancies (n = 17) and complete hydatidiform moles (n = 10). Indirect immunofluorescent staining was performed to detect laminin-1, and Northern blot analysis was performed to assess expression of laminin mRNA. Serum concentrations of laminin P-1 were also measured. Immunohistochemical analysis revealed stronger staining of the trophoblastic basement membrane in hydatidiform mole than in normal pregnancy. Northern blot analysis revealed that villous expression of laminin mRNA was significantly increased in hydatidiform mole compared with normal pregnancy (P < 0.05). The serum laminin P-1 concentration was also significantly higher in those patients with hydatidiform mole than in normal pregnancy (P < 0.05). These results suggest that laminin-1 might play an important role in determining the pathophysiology and structure of hydatidiform mole. In addition, measurement of serum laminin P-1 in combination with human chorionic gonadotrophin might be useful in the diagnosis of hydatidiform mole, to evaluate the prognosis, and to detect the presence of metastatic or recurrent disease.