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Biomedical subjects

M Alini

Publications and source records attributed to M Alini.

26 records · Page 2Linked to original sources
PubMed1995

Cartilage and bone metabolism in rheumatoid arthritis. Differences between rapid and slow progression of disease identified by serum markers of cartilage metabolism.

Serum concentrations of specific cartilage and bone molecules reflecting tissue turnover were measured in two well-defined patient groups with early rheumatoid arthritis with distinctly different disease outcome to see if early differences in their levels are prognostic of the rate of joint destruction. Compared with a matched normal population, increased concentrations of cartilage oligomeric matrix protein (COMP) were found in all patients who developed rapid hip joint destruction. In contrast, levels of a putative marker of cartilage aggrecan synthesis, the chondroitin sulfate epitope 846, were increased only in patients with slow joint destruction. Levels of bone sialoprotein (BSP) were increased in both groups, as were levels of the C-propeptide of type II procollagen (CPII), a marker of collagen II synthesis. The increased concentrations of the 846 epitope in patients with slow joint destruction suggest increased aggrecan synthesis. The low levels of the 846 epitope in patients with rapid joint destruction, concomitant with elevated levels of CPII, suggest a selective increase in collagen synthesis. The elevated BSP levels indicate an increased bone turnover in both groups. Thus elevated serum levels of COMP may indicate an unfavorable prognosis for rapid joint destruction, whereas elevated 846 epitope indicates a more favorable prognosis.

Adult↗
PubMed1994

Cellular and matrix changes before and at the time of calcification in the growth plate studied in vitro: arrest of type X collagen synthesis and net loss of collagen when calcification is initiated.

To understand the growth, maturation, and regulation of growth plate chondrocytes, it is necessary to isolate the different chondrocytes into distinct subpopulations of maturational development. Five subpopulations (A-E) of bovine fetal growth plate chondrocytes were separated by discontinuous gradient centrifugation. Four subpopulations (B, C, D, and E, from low to high density) with good viability were cultured at high density in microwells for up to 30 days. They all established an extensive extracellular matrix composed of proteoglycan and collagen. The largest and last dense cells in subpopulation B were the first to synthesize (at days 5-6) type X collagen and to calcify this matrix. Matrix calcification (formation of hydroxyapatite in the presence of sodium beta-glycerophosphate) always followed the initiation of type X synthesis. All the other subpopulations synthesized type X collagen and calcified their extracellular matrix. Although these events occurred in the same order, they were delayed according to the order of increasing cell size. These observations indicate that these subpopulations represent different stages in cellular maturation that lead to expression of the hypertrophic phenotype. Once mineral formation was well established, there was an increase in the matrix content of the C-propeptide of type II collagen (which is known to bind to hydroxyapatite and accumulate in calcifying extracellular matrix). This was accompanied by a reduction in the total collagen content, which accompanied an abrupt reduction in type X collagen synthesis, whereas type II collagen synthesis was largely maintained. These reductions in collagen content and type II collagen synthesis were not observed in the absence of calcification (beta-glycerophosphate omitted from culture). This new culture system recreates many of the sequential cellular and extracellular changes exhibited in situ during the development of the physis and provides new information about cellular and extracellular matrix changes that occur before and at the time of calcification.

Absorptiometry, Photon↗
PubMed1993

Sulfated proteoglycans in the extracellular matrix of human breast tissues with infiltrating carcinoma.

The size, content and distribution of sulfated proteoglycans, constituents of the extracellular matrix, were investigated in non-neoplastic human breast tissues and in tissues with infiltrating carcinoma. Sulfated proteoglycans were identified as cuprolinic-blue-positive elements on electron microscopy preparations by the method of the critical electrolyte concentration. Morphometric data indicated that the numerical density of PG per surface area (NA) in normal tissues was about 2 to 7 times higher respectively in dense or loose connective zone then that found in the corresponding zones of malignant tissues. By referring to the unit volume of tissue, the overall PG content (Nv) was found to be increased about 5 fold in nonneoplastic tissues. However, in tissues with carcinoma the average length of sulfated proteoglycans was about twice as long in dense and loose connective layers than in the corresponding connective zones of non-neoplastic breast tissues. Our findings provide evidence of profound structural alterations of non-collagenous constituents in the extracellular matrix of human mammary tissues concerned with infiltrating carcinoma.

Adult↗
PubMed1992

The extracellular matrix of cartilage in the growth plate before and during calcification: changes in composition and degradation of type II collagen.

Calcification occurs in the extracellular matrix of the hypertrophic zone of the growth plate when the extracellular matrix volume is reduced to a minimum and alkaline phosphatase content is maximal. The present study shows that significant quantitative and qualitative changes occur in the composition and structure of macromolecules in the extracellular matrix before and during calcification in the proximal tibial growth plate of the bovine fetus. These were detected in part by using microchemical and microimmuno-chemical analyses of sequential transverse frozen sections at defined sites throughout the growth plate. Concentrations of matrix molecules in the extracellular matrix have not previously been determined biochemically. They were measured per unit matrix volume by using combined immunochemical/chemical-histomorphometric analyses. The concentrations within the extracellular matrix of the C-propeptide of type II collagen, aggregating proteoglycan (aggrecan), and hyaluronic acid all progressively increased in the maturing and hypertrophic zones, being maximal (or near maximal) at the time of initiation of mineralization. These results for proteoglycan are contrary to some earlier reports of a loss of proteoglycan are contrary to some earlier reports of a loss of proteoglycan prior to mineralization which measured the tissue content of proteoglycan rather than that present in the extracellular matrix, the volume of which is progressively reduced as the growth plate matures. The C-propeptide data provides a quantitative confirmation of previous immunohistochemical studies. Total collagen concentration (measured as hydroxyproline) in the extracellular matrix initially increased through the proliferating and maturing zones but then rapidly decreased in the hypertrophic zone.(ABSTRACT TRUNCATED AT 250 WORDS)

Acid Phosphatase↗
PubMed1991

Partial characterization of proteoglycans isolated from neoplastic and nonneoplastic human breast tissues.

The biochemical composition of proteoglycans was investigated in human breast tissues of different age either with invasive mammary carcinoma or with benign lesions of the breast. Proteoglycans were extracted from tissues under dissociative conditions (4 M guanidine-HCl), isolated by CsCl gradient ultracentrifugation, and purified by gel exclusion and ion exchange chromatography. Glycosaminoglycan side chain compositions of proteoglycans were evaluated by enzymatic analysis (chondroitinases ABC and AC) and nitrous acid degradation. Biochemical data indicated that proteoglycans of high density and molecular size were increased (per wet weight of tissue) in neoplastic compared to nonneoplastic tissues. Overall proteoglycan content was increased almost 2-fold in tumors. Furthermore, enzymatic data revealed a change in the proportions of glycosaminoglycan chains in neoplastic and nonneoplastic tissues. In particular, an increase in chondroitin sulfate (63% versus 35%, respectively) together with a decrease of dermatan sulfate (12% versus 45%, respectively) characterized tumors in comparison to mammary tissues with benign lesions, while the relative content of heparan sulfate side chains remained similar in both tissues. However, morphometric analyses revealed that heparan sulfate content per epithelial cell volume was in fact decreased in neoplastic tissue. These differences in proteoglycans indicate that there are significant changes in the extracellular matrix and surface properties of cells in breast cancer tissue.

Adult↗
PubMed1991

Characterization of aggregating proteoglycans from the proliferative, maturing, hypertrophic, and calcifying zones of the cartilaginous physis.

The introduction of a new microanalytical approach has made it possible to investigate the molecular structure and content of proteoglycans within the extracellular matrix of the physis when the volumes of the matrix and the cells change before mineralization of the extracellular matrix. By using extracts of serial frozen sections with a combination of gel chromatography and chemical, radioimmunoassay, and morphometric analyses, we demonstrated that, in the bovine fetal physis, the content of large aggregating proteoglycans reaches a maximum in the extracellular matrix of the hypertrophic zone, in the region where calcification begins, at the time when calcification starts. Morphometric analyses revealed that, at this time, the volume of matrix is reduced to a minimum. There was no evidence that the remaining proteoglycans were reduced in size, nor was aggregation changed at the time when calcification was initiated. Thus, contrary to earlier reports, there is no indication that these molecules need to be degraded and removed for calcification to begin, although a progressive loss of proteoglycans clearly occurs as the volume of the matrix is reduced.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

Serum content of the C-propeptide of the cartilage molecule type II collagen in children.

OBJECTIVE: The C-propeptide of cartilage type II procollagen, together with the N-propeptide, are removed from newly synthesized procollagen during collagen fibril assembly in cartilage matrix. The presence and content of the C-propeptide reflect the synthesis of this molecule. Recently, we showed that serum levels of the C-propeptide are increased in adults with rheumatoid arthritis, pointing to increased synthesis of this molecule. In this study we examined its content in the sera of children to determine whether it changes during development. METHODS: Sera were obtained from 44 premature infants (cord blood), 75 children (0-18 years), 14 young adults (18-22 years) and 47 adults (35-60 years). The concentration of serum C-propeptide of type II procollagen was determined by a solution phase competitive inhibition radioimmunoassay which uses a polyclonal antiserum specific for the bovine and human C-propeptide. RESULTS: Compared with adults, concentrations of the C-propeptide of type II procollagen were significantly elevated in children of ages 0-14 years. Concentrations were constant until 10 years of age (premature infants: 14.5 +/- 1.4 ng/ml, mean +/- SE; 0-10 years: 13.6 +/- 1 ng/ml). In children of ages 10-14 years, during which the pubertal growth spurt is ordinarily observed, the mean concentration increased (10-14 years: 21.6 +/- 0.7 ng/ml) although not significantly due to the variation between individuals. Concentrations at all ages younger than 14 were significantly greater than those in older adolescents ages 14-18 (6.3 +/- 0.7 ng/ml), young adults (8.4 +/- 2.0 ng/ml) and adults (5.7 +/- 0.4 ng/ml). Serum concentrations did not show significant differences with respect to sex, but varied from child to child at any given age. CONCLUSIONS: The measurement of this circulating C-propeptide may be of use in studying the biochemical and physiological bases of changes in cartilage turnover in children, and abnormalities thereof.

Adolescent↗