Effectiveness of FibroTouch combined with four hepatic fibrosis biomarkers for evaluation of the liver fibrosis degree among patients with chronic schistosomiasis-induced liver disorders / 中国血吸虫病防治杂志

Objective To evaluate the performance of FibroTouch in combination with four hepatic fibrosis biomarkers for assessment of the degree of hepatic fibrosis among patients with chronic schistosomiasis-induced liver disorders. Methods A total of 63 patients with chronic schistosomiasis-induced liver diseases admitted to The Third People’s Hospital of Kunshan City from January to March 2021 were enrolled as the observation group, while 50 healthy volunteers receiving health examinations in the hospital during the study period were randomly selected as the control group. The liver stiffness measurement (LSM) was determined using the FibroTouch technique, and the serum levels of four hepatic fibrosis biomarkers were detected using chemilumi-nescence immunoassay, including type IV collagen (IV-C), type III procollagen (PC-III), hyaluronidase (HA) and laminin (LN). The receiver operating characteristic (ROC) curves of LSM and four hepatic fibrosis biomarkers alone and in combination for assessing the degree of hepatic fibrosis among patients with chronic schistosomiasis-induced liver disorders were plotted and the area under the ROC curve (AUC) was estimated to examine the value of LSM and four hepatic fibrosis biomarkers alone and in combination for assessing the degree of hepatic fibrosis. Results There were 63 subjects in the observation group, including 28 men and 35 women, and the participants had a mean age of (65.34 ± 12.56) years and a mean body mass index (BMI) of (24.47 ± 11.05) kg/m2. There were 50 subjects in the control group, including 22 men and 28 women, and the participants had a mean age of (64.28 ± 13.10) years and a mean BMI of (25.12 ± 11.64) kg/m2. There were no significant differences between the observation and control groups in terms of gender ratio (χ2 = 0.002, P > 0.05), age (t = 0.437, P > 0.05) or BMI (t = 0.303, P > 0.05). The LSM [(8.65 ± 5.22) vs. (3.24 ± 1.10) kPa; t = 8.013, P < 0.05], IV-C [(51.80 ± 9.45) vs. (30.10 ± 10.34) ng/L; t = 11.506, P < 0.05], PC-III [(77.28 ± 17.22) vs. (48.62 ± 9.54) ng/L; t = 11.224, P < 0.05], HA [(39.55 ± 5.32) vs. (84.89 ± 10.34) ng/L; t = 30.158, P < 0.05] and LN [(99.47 ± 7.37) vs. (61.93 ± 9.80) ng/L; t = 22.496, P < 0.05] were significantly greater in the observation group than in the control group, and Spearman correlation analysis showed that the degree of liver fibrosis positively correlated with LSM (rs = 0.675, P < 0.01), IV-C (rs = 0.421, P < 0.01), PC-III (rs = 0.517, P < 0.01), HA (rs = 0.550, P < 0.01) and LN (rs = 0.539, P < 0.01) among patients with chronic schistosomiasis-induced liver diseases. ROC curve analysis revealed that the AUC of LSM for assessment of the hepatic fibrosis degree was 0.884 (P < 0.001), and the LSM cutoff, sensitivity and specificity were 11.75 kPa, 71.43% and 84.00% at the highest Youden index, respectively. In addition, the AUC of four hepatic fibrosis biomarkers for assessment of the hepatic fibrosis degree was 0.577 to 0.670, with 70.174 to 115.237 ng/L cutoff values, 17.46% to 68.25% sensitivity and 71.01% to 96.00% specificity. In addition, the sensitivity and specificity of LSM combined with four hepatic fibrosis biomarkers were 92.06% and 95.07% for assessment of the hepatic fibrosis degree among patients with chronic schistosomiasis-induced liver diseases. Conclusion FibroTouch in combination with detection of four hepatic fibrosis biomarkers has a high sensitivity and specificity for assessing the degree of hepatic fibrosis among patients with chronic schistosomiasis-induced liver diseases, which deserves widespread clinical uses.

Short-term renal and metabolic effects of low dose vildagliptin treatment added-on insulin therapy in non-proteinuric patients with type 2 diabetes: open-label randomized prospective study

ABSTRACT Objective The aim of this randomized comparative study was to assess renal and metabolic effects of vildagliptin in insulin-treated type 2 diabetes (T2DM) patients without overt chronic kidney disease. Subjects and methods We randomized 47 insulin-treated non-proteinuric patients with satisfactory controlled T2DM and estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73m 2 either to continue insulin therapy (control) or to receive combined insulin-vildagliptin treatment (VIG group). We assessed eGFR using serum creatinine (eGFRcreat), cystatin C (eGFRcys), and both (eGFRcreat-cys), and urinary creatinine-adjusted excretion of albumin (UACR), type IV collagen (uCol IV/Cr), and neutrophil gelatinase-associated lipocalin (uNGAL/Cr) at baseline and after 6 months of treatment. Results Study groups were comparable in terms of age and sex (60.1 ± 6.1 years and 42.9% men in control group vs. 60.8 ± 5.2 years and 39.1% in VIG group). After 6 months of treatment, there were no significant changes in main assessed parameters in control group. VIG group demonstrated significant decrease in HbA1c, diastolic blood pressure, frequency of hypoglycemia, and high-sensitivity C-reactive protein level as compared to the changes in control group. While eGFRcreat, UACR, and uNGAL/Cr showed no significant changes after vildagliptin addition, eGFRcys, eGFRcreat-cys, and uCol IV/Cr changed significantly in comparison with control group (+7.0% [3.7;13.3]; +5.1% [1.4;8.5]; -32,8% [-55.8;-24.4], respectively, p < 0.01 each). Correlation and regression analysis revealed glucose-independent pattern of these changes. Conclusion Addition of vildagliptin to ongoing insulin therapy in patients with T2DM was associated with a reduction in uCol IV/Cr and an increase in eGFRcys and eGFRcreat-cys, independent of T2DM control parameters.

Effects of moderate treadmill exercise on alpha-smooth muscle actin and type iv collagen in the liver of type 2 diabetic rats / 中国组织工程研究

BACKGROUND: Diabetes-induced liver damage is easy to be ignored in the early stage. Exercise therapy can increase the sensitivity of insulin, which is an important means of prevention and treatment of diabetes. OBJECTIVE: To explore the effect of moderate intensity exercise intervention on liver injury during the occurrence of diabetes mellitus. METHODS: The experimental protocol was approved by the Laboratory Animal Care Ethics Committee of Wuhan Sports University. Thirty SPF Sprague-Dawley rats were divided into three groups: normal control group, diabetic control group and diabetic exercise intervention group. Normal control group was fed with normal diet, with no exercise. Diabetes control group was fed with high sugar and high fat diet for 8 weeks, followed by a small dose of streptozotocin (30 mg/kg) injected intraperitoneally, with o exercise. Diabetes exercise intervention group was fed and injected in the same way as diabetes control group, and at the same time carried out moderate intensity treadmill training. After 7 days of streptozotocin injection, hematoxylin-eosin and Masson staining were used to observe the cell morphology, the expression of α-smooth muscle actin was observed by immunohistochemistry, and orbital blood samples were collected to detect the concentration of serum type IV collagen using ELISA. RESULTS AND CONCLUSION: Compared with the normal control group, hematoxylin-eosin staining showed that the structure of liver lobule in the diabetic control group was disordered, a large number of fat vacuoles were seen, and the bile duct in the portal area was obviously proliferated; Masson staining that there were showed fat vacuoles, the structure of liver lobule was seriously damaged, and blue stained collagen fibers were seen in the portal area, and light blue stained collagen fibers were seen between liver cells. The above pathological changes were alleviated in the diabetic exercise intervention group, and the fatty degeneration of liver cells was obviously reduced. The expression of α-smooth muscle actin in the diabetic control group and diabetic exercise intervention group was significantly higher than that in the normal control group (P < 0.05), and that in the diabetic exercise intervention group was significantly lower than that in the diabetic control group (P < 0.05). The level of type IV collagen in the diabetic exercise intervention group was significantly lower than that in the diabetic control group (P < 0.05), to slow down the progress of fibrosis. To conclude, moderate intensity exercise has a good effect on streptozotocin induced liver fibrosis in diabetic rats.

Effects of urantide on expressions of type IV collagen in thoracic aorta and VSMC of atherosclerotic rats / 吉林大学学报(医学版)

Objective: To investigate the effects of urantide on the expressions of type IV collagen (Col IV) in thoracic aorta and vascular smooth muscle cells (VSMC) in the rats with atherosclerosis (AS), and to clarify its mechanism of prevention and treatment of AS Methods: A total of 180 Wistar rats were randomly divided into normal control group (n=30) and AS model group (n=150). The rat models of AS were established by feeding on high-fat diet or intraperitoneally injecting vitamin Da (VDa). The AS model rats were randomly divided into AS group, fluvestation (Flu) group and urantide group (3, 7, and 14 d groups). The expression of Col IV in thoracic aorta wall of the rats was detected by immunohistochemistry. The levels of hydroxyproline (HYP) in serum and urine of the rats in various groups were measured by ELISA. The VSMC were randomly divided into normal control group, urotensin E (U II 10~smol • L_ 1) group, Flu group and urantide (10~10to 10~" mol • L_ 1) groups. The levels of Col IV in VSMC of the rats in various groups were determined by ELISA. Results: There was a significant difference in the expression levels of Col IV in the irregular plaques of the thoracic aorta of the rats between various groups (F = 3 5 . 0 9, P < 0 . 01). The expression levels of Col IV in thoracic aorta of the rats in AS group were significantly increased compared with normal control group (P < 0 . 01); the intensity and extent of Col IV positive staining in urantide group were lower than those in AS group (P < 0 . 01). There were significant differences in the serum and urine HYP levels between various groups (F = 2 4 . 38, P < 0 . 01; F=26. 72, P < 0 . 01). Compared with normal control group, the serum HYP level of the rats in AS group were significantly increased (P < 0 . 01), and the urine HYP level was significantly decreased (P < 0 . 01). Compared with AS group, the serum HYP levels in urantide groups were significantly decreased (P < 0 . 01) and the urine HYP levels were significantly increased (P < 0. 01), no less than the level in Flu group. The expression levels of Col IV in the culture supernatant of VSMC in the rats in various groups had significantly difference (F = 3 1 . 04, P < 0 . 01). The expression level of Col IV in the culture supernatant of VSMC of the rats in U II group was significantly increased compared with normal control group (P < 0 . 01); the expression levels of Col IV in the culture supernatant of VSMC of the rats in urantide groups were significantly decreased compared with U II group (P < 0 . 05 or P < 0 . 01). Conclusion: Urantide can inhibit the expressions of Col IV in the thoracic aorta and VSMC of the AS rats and alleviate the degree of AS lesions, which provides the experimental evidence for the clinical application of urantide in the treatment of AS.

The clinical significance of EGFR,PCNA,LN and type IV collagen expression in salivary adenoid cystic carcinoma / 实用口腔医学杂志

Objective:To investigate the clinical significance of epidermal growth factor receptor(EGFR),proliferating cell nuclear antigen(PCNA),laminin(LN)and type IV collagen expression in salivary adenoid cystic carcinoma(SACC).Methods:EGFR gene in 78 cases of SACC with complete clinical data was detected by fluorescence in situ hybridization(FISH)technique,the expression of EGFR,PCNA,LN and type IV collagen protein was detected by immunohistochemistry technique(IHC),their correlation with the clin-icopathological parameters was analysed by SPSS 13.00 software.Results:EGFR gene amplification levels(69.2%)was positively related to the ratio of EGFR protein positive expression(7 1 .8%),the expression of EGFR,PCNA,LN and type IV collagen was posi-tively related to the clinical pathological parameters(P<0.05).There was a positive correlation between EGFR and PCNA expression (P<0.05),a negative correlation between LN protein and type IV collagen protein expression(P<0.05).Conclusion:EGFR gene is amplified in SACC.EGFR,PCNA,LN and type IV collagen take part in the occurrence and development of SACC.

Effects of fibronectin and type IV collagen on osteosarcoma cell apoptosis.

The aims of this study are the investigation of the effects of fibronectin and type IV collagen extracellular matrix proteins and the role of caspase-3 and -9 on cis-platin induced U2-OS apoptosis were studied. First the cytotoxic effects of cis-platin on cell system were investigated by colorimetric method and than morphological and ELISA analysis were used for determination of cell apoptosis when induced with cis-platin. In addition, after adhering the cells to fibronection or type IV collagen proteins, the apoptotic rate and the effects of caspase-3 and -9 were also investigated by ELISA in presence of specific inhibitors. U2-OS cells showed 20% cytotoxicity after treatment with 2.4 µM of cis-platin for 48 h. Morphological and the numerical data showed that cis-platin was able to induced apoptosis on cells as a dose-dependent manner. Caspase-3 and -9 inhibitors inhibited cis-platin-induced apoptosis in U2-OS cells, respectively. The binding of cells to 10 µg/mL of fibronectin but not type IV collagen enhanced the apoptosis about 2.5 fold that effects inhibited with caspase-3 inhibitor. The caspase-3 and -9 are involved in the apoptotic signals induced by cis-platin in U2-OS. The binding to fibronectin, but not type IV collagen enhanced the apoptotic response of U2-OS and fibronectin-dependent apoptosis was activated by caspase-3. These finding might be useful for patients to fight against osteosarcoma.

Progression of early phase diabetic nephropathy in streptozotocin-induced diabetic rats: Evaluation of various kidney-related parameters.

Diabetic nephropathy (DN) is one of the serious secondary complications of diabetes, which results in end-stage renal failure. Reports on the progressive nature of early phase DN especially with respect to kidney parameters such as kidney weight, type IV collagen excretion, total kidney and urinary glycosaminoglycans (GAGs) are few. This work was undertaken to determine systematically the progression of early phase DN in relation to various kidney-related parameters for a period of four months. Experimentally-induced diabetic rats were grouped based on fasting blood glucose levels. Various basic and kidney-related parameters such as kidney weight, microalbuminuria, urinary excretion of GAGs and type IV collagen, total kidney GAGs, histopathology, glomerular area and glomerular volume were examined in control and diabetic rats. There was a progressive increase in fasting blood sugar, urine sugar, kidney weight, microalbuminuria, urine glycosaminoglycans, urine type IV collagen, glomerular area and glomerular volume but there was a progressive decrease in kidney glycosaminoglycans. Glomerular sclerotic condition was aggravated with the increase in duration of diabetes from 1 to 4 months. Onset of DN in rats begins subtly after one month of diabetes but gets vitiated and more pronounced at the end of four months.

Supraorganized collagen enhances Schwann cell reactivity and organization in vitro

We investigated the reactivity and expression of basal lamina collagen by Schwann cells (SCs) cultivated on a supraorganized bovine-derived collagen substrate. SC cultures were obtained from sciatic nerves of neonatal Sprague-Dawley rats and seeded on 24-well culture plates containing collagen substrate. The homogeneity of the cultures was evaluated with an SC marker antibody (anti-S-100). After 1 week, the cultures were fixed and processed for immunocytochemistry by using antibodies against type IV collagen, S-100 and p75NTR (pan neurotrophin receptor) and for scanning electron microscopy (SEM). Positive labeling with antibodies to the cited molecules was observed, indicating that the collagen substrate stimulates SC alignment and adhesion (collagen IV labeling - organized collagen substrate: 706.33 ± 370.86, non-organized collagen substrate: 744.00 ± 262.09; S-100 labeling - organized collagen: 3809.00 ± 120.28, non-organized collagen: 3026.00 ± 144.63, P < 0.05) and reactivity (p75NTR labeling - organized collagen: 2156.33 ± 561.78, non-organized collagen: 1424.00 ± 405.90, P < 0.05; means ± standard error of the mean in absorbance units). Cell alignment and adhesion to the substrate were confirmed by SEM analysis. The present results indicate that the collagen substrate with an aligned suprastructure, as seen by polarized light microscopy, provides an adequate scaffold for SCs, which in turn may increase the efficiency of the nerve regenerative process after in vivo repair.

Urinary type IV collagen levels in diabetes mellitus

Type IV collagen is the principal component of glomerular basement membrane and messangial matrix. Studies have shown increased levels of urinary type IV collagen (uIV) in diabetic patients compared to healthy controls. The concentration of uIV increases gradually as diabetic nephropathy progresses. Aim and method: This study was carried out to determine whether urinary type IV collagen (uIV) can serve as an indicator of diabetic nephropathy. Using a sandwich enzyme immunoassay technique, uIV excretion was determined in 30 type 2 diabetic patients with normoalbuminuria and 20 patients with microalbuminuria. Results: uIV excretion was signifi cantly increased in type 2 diabetics, in both normoalbuminuric and microalbuminuric patients, compared with healthy controls. The increase in urinary type IV collagen was well correlated with the amount of urinary albumin but not with HbA1C. Conclusion: Our fi ndings that uIV is higher in those with microalbuminuria and correlates with albuminuria, support uIV as an indicator of diabetic nephropathy. Whether the increased uIV excretion would predict the impending renal failure needs further confi rmation.

Edema de Reinke: estudo da imunoexpressão da fibronectina, da laminina e do colágeno IV em 60 casos por meio de técnicas imunoistoquímicas / Reinkes'edema: immunoexpression study of fibronectin, laminin and colagen IV in 60 cases by imunohistochemical techniques

Edema de Reinke é doença crônica da laringe na qual a camada superficial da lâmina própria é expandida por muco espesso conferindo-lhe aspecto gelatinoso. Relaciona-se ao tabagismo e acomete, preferencialmente mulheres, as quais apresentam a voz mais grave. Suas características histológicas nem sempre conseguem diferenciá-lo das demais lesões benignas da laringe, havendo necessidade de técnicas histológicas adicionais. Objetivos: Estudar a imunoexpressão da fibronectina, do colágeno IV e da laminina no edema de Reinke por meio de técnicas imunoistoquímicas. Estudo prospectivo. Material e métodos: Blocos histológicos de 60 casos cirúrgicos de edema de Reinke foram resgatados, submetidos a novos cortes e às reações imunoistoquímicas para fibronectina, laminina e colágeno IV pelo método da Avidina Biotina Peroxidase. Todos os pacientes eram fumantes e adultos, sendo 50 mulheres e 10 homens. Resultados: As análises da imunoexpressão da fibronectina, do colágeno IV e da laminina foram mais expressivas no endotélio dos vasos (68,33 por cento, 76,66 por cento, 73,33 por cento, respectivamente), e menos relevantes na membrana basal (25,0 por cento, 5,0 por cento e 3,3 por cento, respectivamente). Conclusões: No edema de Reinke, a imunoexpressão da fibronectina, da laminina e do colágeno IV na membrana basal não apresentam relevância, havendo predomínio desses anticorpos no endotélio do vasos.

Reinke's edema is chronic laryngeal disease in which the superficial layer of the lamina propria is expanded by thick mucus, giving it a gelatin aspect. The disease is directly related to smoking and more frequent in women, who end up having a lower tone of voice. Its histological characteristics cannot always distinguish it from other benign lesions of the larynx for which additional histological techniques are necessary. AIM: to study the immunoexpression of fibronectin, collagen IV and laminin in Reinke's edema by immunohistochemical technique. Prospective study. Materials and methods: histological blocks of 60 cases of surgical Reinke's edema were saved, submitted to new cross-sections and to immunohistochemical reactions for fibronectin, laminin and collagen IV by the Avidin-Biotin-Peroxidase method. Fragments of five normal vocal folds were used as control, removed during autopsy. All patients were chronic smokers and adults- 50 women and 10 men. Results: the immunoexpression of fibronectin, collagen IV and laminin was more important in the endothelium of blood vessels (68.33 percent, 76.66 percent, 73.33 percent, respectively) and less relevant in the basement membrane (25.0 percent, 5.0 percent and 3.3 percent, respectively). Conclusions: the immunoexpression of fibronectin, laminin and of collagen IV in the basal membrane of Reinke's edema was not relevant, with a predominance of these antibodies in the endothelium of blood vessels.

The Diagnostic Value of Serum Hyaluronic Acid, 7S Domain of Type IV Collagen and AST/ALT Ratio as Markers of Hepatic Fibrosis in Chronic Hepatitis B and Cirrhosis Patients / 대한간학회지

BACKGROUND/AIMS: The prognosis of chronic liver disease is closely related to the development of hepatic fibrosis. Liver biopsy is the gold standard method to assess inflammatory activity and fibrosis stage, but this is associated with morbidity and mortality. This study aimed to evaluate the diagnostic value of serum hyaluronic acid, 7S domain of type IV collagen and AST/ALT ratio as markers of hepatic fibrosis in chronic hepatitis B and cirrhosis. METHODS: This study included 100 patients with chronic hepatitis B and cirrhosis. Liver biopsy and histopathologic classification were done. Serum hyaluronic acid and 7S domain of type IV collagen were measured by one step sandwich binding protein assay and radioimmunoassay using polyclonal antibody to 7S domain of type IV collagen, respectively. RESULTS: The serum concentrations of hyaluronic acid, 7S domain of type IV collagen and AST/ALT ratio in the cirrhosis group (139 +/- 98.4 ng/mL, 6.9 +/- 3.5 ng/mL, 1.6 +/- 1.5) were significantly higher (p<0.01) than those in the normal and fatty liver group (20.2 +/- 12.5 ng/mL, 3.5 +/- 0.5 ng/mL, 0.7 +/- 0.3), mild hepatitis group (32.3 +/- 52.7 ng/mL, 3.9 +/- 1.4 ng/mL, 0.7 +/- 0.4), and moderate to severe hepatitis group (68.2 +/- 72.3 ng/mL, 5.3 +/- 2.4 ng/mL, 0.8 +/- 0.4). At the cutoff value of 77 ng/mL for hyaluronic acid and 6.3 ng/mL for 7S domain of type IV collagen and 0.62 for AST/ALT ratio, the sensitivities were 81.8%, 63.6%, 90.9% and specificities were 87.3%, 88.6%, 53.1% for discriminating cirrhosis (fibrosis score: 4) from the mild to severe fibrosis (fibrosis score: 0-3). CONCLUSIONS: Serum hyaluronic acid, 7S domain of type IV collagen and AST/ALT ratio measurement may be clinically useful as markers of hepatic fibrosis in chronic hepatitis B and cirrhosis.

Role of Transforming Growth Factor beta Induced by Podocyte in the Pathogenesis of Diabetic Nephropathy / 대한신장학회잡지

BACKGROUND: According to the development of methods in podocyte cell culture several studies for the role of podocyte in the progression of glomerulosclerosis have been recently reported. But there is few report for the regulation of TGFbeta1 synthesis and type IV collagen production in podocyte in diabetic nephropathy. We investigated the effects of high glucose and TGFbeta1 in culture medium on TGFbeta1 and type IV collagen production and whether their production is dependent on protein kinase C (PKC) pathway in cultured mouse podocyte cell line. METHODS: Conditionally immortalized mouse podocytes with a temperature-sensitive variant of SV40 large T antigen were cultivated. To propagate podocytes, cells were cultivated at 33 degrees C and treated with gamma-interferon (permissive condition). And to induce differentiation, podocytes were changed at 37 degrees C and deprived of gamma-interferon (non-permissive condition). The effects of high glucose and TGFbeta1 in culture media on procollagen alpha1 (PCalpha1 (IV)) and their relationships to PKC pathway were examined. The mRNA expression and protein production of TGFbeta1 and PCalpha1 (IV) were assayed by reverse transcription - polymerase chain reaction (RT-PCR) and western analysis. RESULTS: Compared with normal glucose (NG, 5.5 mM), high glucose exposure (HG, 15, 30 mM) increased the mRNA expression and protein production of TGFbeta1 and PCalpha1 (IV), but without a statistic significance: TGFbeta1 (after 6 hours: 69.62+/-9.00 vs 83.48+/-7.82 vs 74.49+/-24.73, after 24 hours: 65.06+/-20.55 vs 68.01+/-24.35 vs 94.23+/-13.14), PCalpha1 (IV) (after 6 hours: 109.94+/-10.43 vs 102.00+/-6.68 vs 138.65+/-39.83, after 24 hours: 105.88+/-9.53 vs 83.95+/-1.12 vs 109.14+/-3.29, after 72 hours: 99.18+/-5.30 vs 92.93+/-6.33 vs 109.25+/-4.11). TGFbeta1 significantly decreased the expression of PCalpha1 (IV). Calphostin C treatment further stimulated the increase of PCalpha1 (IV) production induced by HG and inhibited the decreased mRNA expression of PCalpha1 (IV) induced by TGFbeta1 administration. CONCLUSION: We suggest that TGFbeta1 have an important role in podocyte in the pathogenesis of diabetic nephropathy. The HG-induced increases of procollagen alpha1 type IV collagen seems to be negatively regulated by TGFbeta1 and PKC pathway and possibly another pathway will positively regulate the production of PCalpha1 (IV), and these pathways may have a different effect on collagen synthesis dependent on the renal cell type.

Relationship Between Vascularity and Other Remodeling Parameters in Asthmatic Airway / 결핵

BACKGROUND: The pathological features in asthmatic airway remodeling are diverse. The aim of this study was to examine the degree of airway vascularity in relation to the other remodeling parameters in asthmatics. METHODS: Bronchial biopsies were done in 34 asthmatic patients, and 6 control subjects. The basement membrane thickness and the subepithelial thickness were measured in the hematoxylin-eosin stained tissue, and the degree of vascularity was measured using type IV collagen immunostaining. RESULTS: 1) Compared to the control subjects, the asthmatics showed a significant increase in the basement membrane thickness (6.92+/-2.01micrometer vs 9.67+/-2.84micrometer, p<0.05) and the subepithelial thickness (44.49 +/- 31.92micrometer vs 121.22+/-72.79micrometer, p<0.05). 2) Compared to the control subjects, the asthmatics showed a significant increase in the vascular area per unit submucosal area (4.51+/-2.13% vs 10.32+/-6.08%, p<0.05). In addition, the number of vessels per unit submucosal area showed an increased tendency without statistical significance. 3) In the asthmatics, the number of vessels and the vascular area per unit submucosal area showed no correlation with the basement membrane thickness, the subepithelial thickness, the severity, the forced expiratory volume in 1 second(FEV1), and the methacholine provocative concentration 20(PC20). CONCLUSION: This study showed that vascularity was an important parameter in asthmatic airway remodeling but it was not related to the other remodeling parameters such as the basement membrane thickness and the subepithelial thickness. Each of these asthmatic remodeling parameters may have a different clinical significance. Therefore, further studies will be needed.

Immuno-expression of Type IV Collagen in the Intervertebral Disc / 대한척추외과학회지

STUDY DESIGN: In vitro studies using human intervertebral disc for the localization of the type IV collagen. OBJECTIVE: 1) To study the distribution pattern and immunoexpression of type 4 collagen in the intervertebral disc, 2) To study the function of type IV collagen in the intervertebral disc. SUMMARY OF BACK GROUND: The correlations of degeneration changes and collagens in the dics have not been determined. The reports for type IV collagen were few. So far, the histologic analysis for the expression of type IV collagen in the intervertebral disc has not been done. There was no report to study the function of the type IV collagen in the intervertebral disc. METHODS: Fifty-four disc blocks obtained during anterior interbody fusion of the lumbar spine were used to observe the expression pattern of the type IV collagen with immunochemical stain. For the observation of the myxomatous degeneration in the intervertebral disc, the alcian blue stain with periodic acid-schilff was done. For the control group, 22 neonate intervertebral disc blocks were obtained at autopsy. RESULTS: The immunoreactions for type IV collagen were associated blood vessels in the anulus fibrosus in the disc. There was no statistical significant difference of the type IV collagen expression between the control and disease groups. Myxomatous degenerations were observed as the irregular form in the degenerative intervertebral disc. CONCLUSION: The immunoreactions for the type IV collagen were observed in the intervertebral discs and associated with the formation of the blood vessels, especially in anulus fibrosus.

Assessment of Wall Structure and Composition of Varicose Veins

PURPOSE: Valvular incompetence and venous wall abnormalities have been suggested as primary etiologic factors responsible for the development of varicose veins. The valvular theory is known that the continuous gravitational pressure result in varicose vein. There are controversy about this theory. The collagen and elastic fiber have important role of maintaining structure and differentiation of vein. The authors reported on the factor affecting change of venous wall structure in varicose vein. METHOD: The present study describes the histopathologic aspects of varicose (n=10; mean age, 41.2 years) and normal saphenous veins (n=6; mean age, 55.3 years) of patients using H-E stain, Van-Gieson stain, Verhoeff stain, and type IV collagen immunohistochemical stain, and examined by light microcopy. RESULT: In H-E stain, venous wall distension, large amount smooth muscle cell, expansion of extracellular matrix, and a number of endothelial cells were seen. In Van-Gieson stain, the volume of smooth muscle cell increased especially in subendothelial layer and medial layer. The collagen increased in subendothelial and medial layer. The arrangement of smooth muscle cells was broken down due to infiltration of collagen fiber between the smooth muscle cells. In Verhoeff stain, the elastic fiber was scatterd irregularly in the wall of varicose vein. The elastic fiber increased in small amount within intimal layer, but there was no significant change comparison to control group. In type IV collagen immunohistochemical stain, there was intense expression of type IV collagen within medial layer of control. The expression was decreased in varicose vein. The type IV collagen gradually disappeared from medial layer close to adventitia. CONCLUSION: The compositions of collagen, elastic fiber, and smooth muscle cell in varicose vein may be different from that of vessel wall in normal vein in same level in the effect of same pressure. The results suggest that the etiology of varicose vein may depend on abnormal response of vessel wall from injury rather than valvular incompetence.

Diagnostic value of serum type IV collagen in hepatic fibrosis / 西安交通大学学报(医学版)

ObjectiveTo study the diagnostic value of serum type IV collagen(IV-C) in hepatic fibrosis. MethodsSerum IV-C levels were detected by using radioimmunoassay(RIA) and were compared with serum type Ⅲ procollagen(PCⅢ ) levels in normal controls(NC) and patients with chronic liver diseases. ResultsSerum IV-C and PCⅢ levels in patients with chronic liver diseases were all much higher than those in NC(P < 0.01, totally). Serum IV-C level in severe chronic hepa titis(CH) group was significantly higher than those in mild and median CH groups (P<0.01 total ly), and that in active liver cirrhosis(LC) group was significantly higher than that in static LC group (P＜0.05). There were significant positive correlation between serum IV-C level and serum PcⅢ level both in CH group and in LC group ( in CH γ=0.7023, in LC γ=0. 5878, P＜0. 001).Conclusion Serum IV-C level could reflect the activity of hepatic fibrogenesis.

A Double Immunohistochemical Study on the Expression of Matrix Metalloproteinase-2 and Type IV Collagen in Squamous Cell Carcinoma of the Oral Cavity and Oropharynx / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Matrix metalloproteinase-2 (MMP-2) is produced by tumor cells that specifically cleaves type IV collagen, one of the major constituents of basement membrane. The MMP-2 and type IV collagen have been postulated to have an important role in the invasion and spread of malignant tumors. However, little has been reported about expression of MMP-2 and type IV collagen in primary tumors and metastatic lymph nodes of oral cavity and oropharynx simultaneously. So we investigated that MMP-2 and type IV collagen can be used as the prognostic indicators of metastasis in squamous cell carcinoma of oral cavity and oropharynx. MATERIALS AND METHODS: Double immunohistochemistry was used to detect MMP-2 and type IV collagen in 32 primary tumors (14 cases had metastatic nodes and 18 cases had no metastatic node) of surgically treated squamous cell carcinoma of the oral cavity and oropharynx. The findings were compared to clinical findings of each cases. RESULTS: The immunoreactivity of MMP-2 increased significantly as more destructive patterns of basement membrane components in primary tumor (p=0.019) than metastatic lymph nodes. The cases with cervical metastasis showed more destructive patterns than cases with absence of cervical metastasis in primary tumor (p=0.003), but expression of MMP-2 had no correlation with presence or absence of cervical metastasis. The cases with diffuse invasion showed more destructive pattern than cases with any other patterns in primary tumor. However, expression of MMP-2 had no correlation with invasion mode of primary tumor. In metastatic lymph node, neither of them had no correlation with invasion mode. No statistical correlations in expression of MMP-2 and type IV collagen were detected between primary tumor and metastatic lymph nodes. CONCLUSION: The expression patterns of MMP-2 and type IV collagen in oral cavity and oropharyngeal squamous cell carcinoma can be useful in predicting cervical metastasis.

Immuniohistochamical study of the distribution of laminin, fibronectin, and type IV collagen on the palate epithelium with respect to rugae development / 대한해부학회지

The basement membrane, as a specialized form of extracellular matrix, is known to influence the development and differentiation of several kinds of organs and tissues. The development of palatal rugae involves morphological changes of oral epithelium, basement membrane (BM), and mesenchymal tissue and, thus, is thought to be one of the model systems of embryonic development. The BM is thought to influence also the rugae development and defferentiation. If so, the components of the BM would change during rugae development. This study was performed to observe the changes of laminin, fibronectin, and collagen type IV in the oral BM during the fetal ages 16~21 by immunohisto-chemistry. The stainability to laminin began to disappear at the anterior portion of the palate on day 17, and at the end of the gestation showed hardly the immunoreactivity to laminin. Along with the decrease of the stainability through the oral apithlium, the BM of rugae area revealed more decreased reactivity to laminin compared to inter-rugal area and such a phenomina could be observed with anterior rugae first and with the middle and posterior rugae thereafter. The stainin pattern of fibronectin was also similar to that of laminin. In case of collagen IV, it maintained the immunoreac-tivity tro collagen IV with a little decrease at the anterior rugae on day 21 of gestation. As was observed, the components of BM, especially the laminin and fibronectin, changed in its immunoreactivity in parallel to the development of the rugae, which enables us to suggest their relationship to the development and differentiation of the rugae.

The Clinical Significance of Serum Hyaluronic Acid and Type IV Collagen Level in Chronic Hepatitis and Early Liver Cirrhosis / 대한간학회지

BACKGROUND/AIMS: Liver biopsy has been used to evaluate the degree of hepatic fibrosis in patients with chronic liver diseases. It is important to assess liver fibrosis when following the course of chronic liver diseases. Histopathological examination of percutaneous biopsy specimens is invasive and is also of questionable value because of the heterogenous distribution of pathological changes in the liver. Therefore, non-nvasive methods to determine the progress of liver fibrosis are needed. Serum hyaluronic acid and type IV collagen are known to be related to hepatic fibrosis. This study was performed to evaluate the clinical usefulness of serum hyaluronic acid and type IV collagen measurement as a differential point in patients with chronic liver diseases and early cirrhosis. METHODS: This study included 109 patients with chronic liver diseases caused by various etiologies. Liver biopsy and histopathological classification were done in all patients. Serum hyaluronic acid and type IV collagen were measured by one-tep sandwich binding protein assay and one-tep sandwich enzyme immunoassay. RESULTS: The concentrations of hyaluronic acid and type IV collagen in the early cirrhosis group (208.5+/-186.4 ng/mL, 242.1+/-162.8 ng/mL) were significantly higher (p<0.01) than those in the normal and fatty liver group (26.3+/-21.7 ng/mL, 79.2+/-28.8 ng/mL), mild chronic hepatitis group (22.8+/-15.4 ng/mL, 125.5+/-79.7 ng/mL), moderate to severe hepatitis group (66.3+/-60.5 ng/mL, 148.5+/-78.7 ng/mL). At the cutoff value of 100 ng/mL for hyaluronic acid and 200 ng/mL for type IV collagen, the sensitivities were 66.7% and 55.6%, and specifities were 82.9% and 89%, and diagnostic efficiencies were 78.9% and 80.7% respectively for discriminating patients with cirrhosis (4 points) from the mild to severe fibrosis (0~3 points). CONCLUSIONS: The serum levels of hyaluronic acid and type IV collagen may be sensitive markers of fibrotic process in chronic liver diseases and useful biochemical markers in differentiation of the patients with early cirrhosis from those with chronic liver diseases.

Expression of Matrix Metalloproteinase-1,2,3 and Type IV Collagen in Gastric Adenocarcinoma: Influence on Lymph Node Metastasis and Prognosis

Matrix metalloproteinases are believed to play an important role in tumor invasion and metastasis. But little is known about the role of them in the gastric adenocarcinoma. We investigated the expression of matrix metalloproteinase-1,2,3 in eighty paraffin blocks of the primary gastric adenocarcinoma tissues with immunohistochemistry and analysed their correlation with lymph node metastasis and survival. MMP-1,2,3 were expressed most intensely in the fibroblasts around the tumor stroma. In our study the increased immunoreactivity of MMP-2 only showed statistically significant correlation with lymph node metastasis (P=0.0517, Odd's ratio=2.274). But MMP-1,2,3 all were correlated with survival. Type IV collagen was observed in the vascular basement membranes and tumor basement membranes and showed statistically significant correlation with lymph node metastasis (P=0.0002, Odd's ratio=0.194) and prognosis (P=0.0001). The immunoreactivity of MMP-2 and type IV collagen was inversely correlated (Kendall's Tau-b correlation = 0.37482, P=0.0001). Our results suggest that in human gastric adenocarcinoma the increased immunoreactivity of MMP-2 and the decreased immunoreactivity of type IV collagen has an important role in lymph node metastasis and prognosis. MMP-1,3 are not correlated with lymph node metastasis but correlated with survival. The mechanism responsible for the production of MMP by the host fibroblasts remains obscure and requires further investigation.