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Biomedical subjects

M J Glimcher

Publications and source records attributed to M J Glimcher.

At least 127 records · Page 7Linked to original sources
PubMed1983

Biosynthesis of O-phosphoserine-containing phosphoproteins by isolated bone cells of mouse calvaria.

Five groups of isolated bone cells from mouse calvaria were incubated with [3H]serine and the presence and amount of O-[3H]phosphoserine used as an indication of phosphoprotein synthesis. Cells in the osteoblastic fraction were the most active in synthesizing phosphoproteins, and unlike the other cell groups, released most of the phosphoproteins into the tissue culture medium. When subjected to molecular sieving and ion-exchange chromatography, the phosphoproteins synthesized by the bone cells of the osteoblastic group behaved like the phosphoproteins extracted from mouse calvaria by EDTA.

Animals↗
PubMed1983

Differences in the extent and heterogeneity of lysyl hydroxylation in embryonic chick cranial and long bone collagens.

The hydroxylation of lysine in embryonic chick long bone and mandibular collagen was found to be approximately 3-fold greater than that of the collagens of adult animals. In contrast, no significant difference was found in extent of lysine hydroxylation of the collagens of frontal bones of embryos and postnatal animals. Both histochemical and biochemical evidence established that full thickness diaphyseal bone samples contained cartilage and, consequently, type II collagen which undoubtedly contributed to the higher hydroxylysine contents of young postnatal animals reported previously. DEAE ion exchange chromatography of the alpha 1(I) chains of lathyritic long bone and mandibular collagens isolated by carboxymethyl-cellulose ion exchange chromatography showed considerable heterogeneity, whereas the alpha 1(I) chains obtained from lathyritic frontal bone collagen did not. Three fractions of alpha 1(I) chains of long bones and mandibular collagen were isolated which differed significantly in their hydroxylysine contents. The relative proportion of the three peaks changed as a function of embryonic age and maturation: more of the alpha 1(I) chains with the highest hydroxylysine content was present in the collagen synthesized earliest during embryonic development. This is consistent with results which demonstrated that the collagens synthesized earliest during embryonic and postnatal development had the highest hydroxylysine contents.

Aging↗
PubMed1983

X-ray diffraction studies of the crystallinity of bone mineral in newly synthesized and density fractionated bone.

The crystallinity of bone mineral at different stages of maturation has been measured by quantitative X-ray diffraction methods. Crystallinity measurements were made on tibial mid-diaphyses from 17-day embryonic chicks, newly-formed periosteal bone from embryonic chicks, and density-fractionated bone from post-hatch chickens from 5 weeks to 2 years of age. For a given animal age and degree of mineralization, crystallinity increases with animal age, indicating that changes in bone mineral occur even after mineralization is complete or nearly complete.

Age Factors↗
PubMed1983

31P nuclear magnetic resonance spectroscopic evidence for ternary complex formation of fetal dentin phosphoprotein with calcium and inorganic orthophosphate ions.

The single phosphoprotein of fetal calf dentin, having a molecular weight of approximately 94,000 and a phosphorus content of 8% (w/w), was examined by 31P NMR spectroscopy. The single resonance at 3.7 ppm at pH 10 and its chemical shift during acid titration established the phosphomonoester nature of the organic phosphorus moiety. During titration of the phosphoprotein with CaCl2 in the presence of inorganic orthophosphate ions, line broadening for the orthophosphate resonance was both phosphoprotein- and calcium-dependent, indicating ternary complex formation. The data indicate that the phosphoprotein of fetal calf dentin binds both calcium and inorganic orthophosphate ions and therefore has the requisite physical chemical properties necessary for it to facilitate the heterogeneous nucleation of a Ca-PO4 solid phase from solution during tissue mineralization.

Animals↗
PubMed1982

Changes in phosphoproteins of chicken bone matrix in vitamin D-deficient rickets.

Vitamin D-deficiency and rickets was produced in growing chicks. The resulting decrease in mineralization of whole bone and of fractions separated by density centrifugation was accompanied by a very significant decrease in the contents of O-phosphoserine and O-phosphothreonine. Likewise, the total amount of O-phosphoserine and O-phosphothreonine and the concentrations of these phosphoamino acids in EDTA extracts and in fractions obtained by molecular sieving was also reduced. These data provide the first in vivo evidence that phosphoproteins may be critically involved in the calcification of bone.

Animals↗
PubMed1982

Alterations of the gamma-carboxyglutamic acid and osteocalcin concentrations in vitamin D-deficient chick bone.

The content of osteocalcin and protein bound gamma-carboxyglutamic acid (Gla) was studied as a function of bone maturation and mineralization in normal and vitamin D-deficient, rachitic chickens. The Gla/Ca2+ ratio was elevated in rachitic bone, particularly in the most undermineralized regions. For example, there is a 10- to 20-fold elevation in Gla/Ca2+ in the newly synthesized, least mineralized rachitic bone fraction, which progressively decreases to a 1.5-fold elevation in the most highly mineralized areas of rachitic tissue. Osteocalcin, which is the principal Gla-containing protein of mature bone, was quantitated by radioimmunoassay using specific antiserum to the 5670-dalton chicken protein. Surprisingly, the osteocalcin concentration is decreased 50% in vitamin D-deficient bone. From this we infer that accumulated Gla-containing protein in vitamin D-deficient and poorly mineralized bone may possibly represent a precursor of osteocalcin.

1-Carboxyglutamic Acid↗
PubMed1982

Concentrations of osteocalcin and phosphoprotein as a function of mineral content and age in cortical bone.

The contents of two classes of calcium binding proteins of bone matrix, osteocalcin and phosphoprotein, were measured as a function of age of the animal and of the mineral content of chicken bone powder, fractionated according to particle density by differential centrifugation in bromoform-toluene solutions. Whole bone and separated fractions were analyzed for gamma-carboxyglutamic acid (Gla) and for O-phosphoserine [Ser(P)] as indications of their osteocalcin and phosphoprotein contents, respectively. Except for the Ser(P)/collagen ratio of 2-year-old chicken bone, the concentrations of Gla and Ser(P) in the organic protein matrix of the bone increased with increasing mineral content of the tissue, calculated on the basis of the total protein content, the noncollagenous protein content, and the collagen content of the tissue sample. However, a significant difference was found between the concentrations of Gla and Ser(P) with respect to the calcium content of the tissue. The Gla concentration remained relatively constant, whereas the Ser(P) concentration decreased markedly with increasing calcium content. This may reflect the fact that the two classes of proteins have different biological functions and are concentrated in the tissue by different physical chemical mechanisms.

Aging↗
PubMed1982

The reaction of cartilage and osteophyte formation after the intraarticular injection of papain.

A histological and autoradiographical study on the reaction of chondrocytes and the growing processes of osteophyte after the intraarticular injection of papain was carried out. The degenerating processes--fibrillation, death of chondrocytes and erosion--were observed as early as 1 day after the injection, and acid mucopolysaccharide staining with safranin-O was completely lost throughout the articular cartilage 1 week after the injection. The regenerating or proliferating figures--chondrocytes mitosis, thickening of fibrous tissue--were observed as early as 3 days after the injection and chondrocyte clusters were noted after 1 week of injection. Four weeks after injection, proliferating processes were more obvious than degenerating processes, safranin-O stainability had recovered and the proliferative figures of cartilage and fibrous tissue became more obvious. As blood vessels invaded into the cartilage and thickened fibrous tissue, osteophyte began to form in these tissues. Four types of growing processes of osteophyte were observed. Hypertrophy of articular cartilage was observed, and new hyaline articular cartilage appeared to be formed through metaplasia from fibrous tissue. Including the osteophyte formation, tremendous regenerating or repairing efforts of chondrocytes and fibroblasts were observed. These results appear to indicate that cartilage has some ability to regenerate and to repair itself if it could avoid further damage.

Animals↗
PubMed1981

Serine phosphate, threonine phosphate and gamma-carboxyglutamic acid in normal and experimentally induced, pathologically calcified rat skin (topical cutaneous calciphylaxis).

The amount of non-collagenous proteins is increased greatly during the pathological calcification of rat skin experimentally induced by dihydrotachysterol (DHT) and Ovalbumin (topical cutaneous calciphylaxis). This is accompanied by an increase in the total amount and concentrations of protein-bound serine phosphate [Ser(P)], threonine phosphate [Thr(P)] and gamma-carboxyglutamic acid (Gla), almost all of which can be extracted from the tissue and can be dissociated from collagen in 0.5M EDTA. The EDTA-soluble, non-collagenous proteins are rich in aspartic and glutamic acids, similar to the non-collagenous, EDTA-soluble proteins of bone, cementum and calcified cartilage, and quite distinct from those of dentin and enamel.

1-Carboxyglutamic Acid↗
PubMed1981

Purification, composition, and 31P NMR spectroscopic properties of a noncollagenous phosphoprotein isolated from chicken bone matrix.

Fractionation of the EDTA-soluble, noncollagenous proteins of the organic matrix of chicken bone by Sephadex G-100 molecular sieving has revealed that the majority of the organic phosphorus is present in two fractions, from one of which a homogeneous phosphoprotein has been isolated. The purified phosphoprotein has an apparent molecular weight of 12,000 and contains both O-phosphoserine and O-phosphothreonine. 31P-NMR spectroscopy demonstrates that all of the organic phosphorus exists in the form of phosphomonoesters which have an average pK2 of 6.8. The phosphoprotein is highly acidic due to its high content of dicarboxylic acids in addition to the presence of organic phosphorus. The characteristic amino acid composition of the phosphoprotein establishes its noncollagenous nature and highlights the differences among bone, dentin, and enamel phosphoproteins. The absence of gamma-carboxyglutamic acid distinguishes it from osteocalcin, the noncollagenous gamma-carboxyglutamic acid-containing peptide of bone matrix.

Amino Acids↗
PubMed1981

[Biology of the femoral head necrosis. Clinical studies (author's transl)].

From the study of femoral heads either experimental or human it is clear that the clinico-pathological called idiopathic necrosis is due to the death of bone cells, as it is in necrosis after fracture or dislocation. But the cause of cell's death is clearly avascular only in traumatic necrosis: in idiopathic necrosis there is no evidence of arterial alteration or obliteration, whatever condition is associated. In both avascular (traumatic) necrosis, and idiopathic necrosis, the cartilage remains alive: the deformation of the head, secondary rupture and destruction of cartilage and finally osteoarthritis are the consequence not of the death of bone cells (a dead head with living cartilage would work for along time) but of the revascularisation process. This process is different in the two syndrome. In idiopathic necrosis proliferation of living tissues in the head is active, but bone formation is limited, shearing forces create a subchondral fracture in the dead part of the head. In avascular necrosis, after the fracture is united, proliferation invades the dead head, with active osteogenesis. The pathological fracture is between dead and bone and revascularised part of the head. One can suggest as therapeutic measure the prevention of revascularisation.

Cell Survival↗
PubMed1981

Biochemical changes in the collagen of the palmar fascia in patients with Dupuytren's disease.

The palmar fascial tissues of more than 400 patients with Dupuytren's disease were studied biochemically and compared with normal tissue obtained from more than 100 patients who were undergoing hand surgery for other reasons. No alterations of the molecular structure or the state of macromolecular aggregation of the collagen in Dupuytren's disease were detected by wide or low-angle x-ray diffraction studies or by transmission electron microscopy. Major biochemical changes in the palmar fascia affected by Dupuytren's disease included increased collagen and hexosamine contents and the presence of galactosamine in the most severely involved tissue. Type-III collagen, which is virtually absent from normal adult palmar fascia, was abundant in the tissue of patients with Dupuytren's disease. Post-translational modifications included a very elevated hydroxylysine content, an increase in the total number of reducible cross-links, and the appearance of hydroxylysinohydroxynorleucine (virtually absent from normal palmar fascia) as the major reducible cross-link. Even palmar fascia from patients with Dupuytren's disease that appeared grossly and histologically normal showed the same biochemical changes, albeit to a lesser extent. All of these biochemical changes are similar to those that occur during the active stages of connective-tissue wound repair. This includes the rapid synthesis and turnover of collagen which leads to newly synthesized, immature collagen being more abundant in the involved tissue than in normal tissue. There is no evidence that the gross, macroscopic contracture of the palmar fascia in Dupuytren's disease is due to shortening, plication, or contraction of the collagen fibrils or fibers present in the tissue at the onset of the disease or synthesized during its development. Instead, we propose that the gross contracture (shortening) of the palmar fascia in Dupuytren's disease is due to an active cellular process that progressively draws the distal extremities of the affected tissue closer together at the same time that the original tissue is being replaced. The result of these two processes is simply a shorter, smaller piece of tissue fabric containing collagen molecules, fibrils, and fibers of normal length and organization, but with pretranslational and posttranslational modifications similar to those observed in collagens during the active stages of connective-tissue repair in general.

Adult↗
PubMed1980

Magic angle sample spinning in inhomogeneously broadened biological systems.

Recent advances in magic angle sample spinning experiments now permit observation of dilute spin high resolution n.m.r. spectra of arbitrary powder samples. In the 'slow-spinning' régime, for which the spinning rate is less than the size of the interaction that is being averaged, the spectra exhibit rotational side bands whose intensities contain information on chemical shift anisotropies. A technique for extracting shift anisotropies from side band intensities is discussed. Since many biologically interesting systems are solid or semi-solid in nature, this technique should find wide application to biological systems. Two illustrations of the point are given in this paper, namely, n.m.r. studies of membranes and of the phosphate-containing phases of bone.

Animals↗