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Connective tissue activation. XVII. Radioimmunoassay of a human platelet derived connective tissue activating peptide (CTAP-III) and specificities of anti-CTAP-III sera.

The platelet-derived connective tissue activating peptide (CTAP-III) has been shown to be an important factor stimulating the metabolism and proliferation of human connective tissue cell strains, including synovial tissue cells. The quantities of CTAP-III affecting the cellular changes and the amounts of various biologic fluids and tissues are small. The objectives of this study were to develop a radioimmunoassay (RIA) for CTAP-III and to ascertain the specificities of the anti-CTAP-III sera reagents. The antisera were shown not to cross-react with a number of polypeptide hormones. However, two other platelet proteins, beta-thromboglobulin and low affinity platelet factor-4, competed equally as well as CTAP-III for anti-CTAP-III antibodies in the RIA system. Thus, the three platelet proteins are similar or identical with respect to those portions of the molecules constituting the reactive antigenic determinants. The levels of material in normal human platelet-free plasma that inhibited anti-CTAP-III--125I-CTAP-III complex formation were determined to be 34 +/- 13 (S.D.) ng/ml.

Animals↗

Connective tissue activation. XXXII. Structural and biologic characteristics of mesenchymal cell-derived connective tissue activating peptide-V.

Connective tissue activating peptide-V (CTAP-V) is a single-chain, mesenchymal cell-derived anionic protein with large and small molecular forms (Mr of 28,000 and 16,000, respectively), as defined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The proteins have similar specific activities with respect to stimulation of hyaluronic acid and DNA formation in human synovial fibroblast cultures. S-carboxymethylation or removal of sialic acid residues did not modify CTAP-V biologic activity. Rabbit antibodies raised separately against each of the purified CTAP-V proteins reacted, on immunodiffusion and on Western blot, with each antigen and neutralized mitogenic activity. The amino-terminal amino acid sequence of the CTAP-V proteins, determined by 2 laboratories, confirmed their structural similarities. The amino-terminal sequence through 37 residues was demonstrated for the smaller protein. The first 10 residues of CTAP-V (28 kd) were identical to the N-terminal decapeptide of CTAP-V (16 kd). The C-terminal sequence, determined by carboxypeptidase Y digestion, was the same for both CTAP-V molecular species. The 2 CTAP-V peptides had similar amino acid compositions, whether residues were expressed as a percent of the total or were normalized to mannose. Reduction of native CTAP-V protein released sulfhydryl groups in a protein:disulfide ratio of 1:2; this suggests that CTAP-V contains 2 intramolecular disulfide bonds. Clearly, CTAP-V is a glycoprotein. The carbohydrate content of CTAP-V (16 kd) and CTAP-V (28 kd) is 27% and 25%, respectively. CTAP-V may have significance in relation to autocrine mechanisms for growth regulation of connective tissue cells and other cell types.

Acetylglucosaminidase↗

[Superposition syndrome of connective tissue diseases: current view with special focus on mixed connective tissue disease].

Attention is called to mixed connective tissue disease which, twenty years after it's original description, has now reached the syndromic individualization with important therapeutic and prognostic implications. In particular the discussion concerns the pulmonary complications (hypertension and fibrosis) responsible frequently for fatal outcome.

Humans↗

[Reconsideration of the bilaminar zone in the retrodiscal connective tissue of the TMJ. 2. Fibrous structure of the retrodiscal connective tissue and relation between those fibers and the disk].

The fibrous structure of the retrodiscal connective tissue was investigated histologically in order to reconfirm what Rees calls the bilaminar zone. Eleven TMJs were taken from the fresh cadavers. The sections, obtained from six materials with condyle protruded, were observed mainly. The Results were as follows: The retrodiscal area was composed of the collagen fibers originating into this area from the petrotympanic fissure, from the conjunctive area of the posterior wall of the fossa with the lateral wall of the articular cavity, and from the conjunctive area of the posterior slope of the auricular tubercle with the lateral wall of the articular cavity. In the superficial layer of the retrodiscal area, these fibers crossed each other, and a few fibers jointed with these fibers from the superficial layer of the disk and from the posterior wall of the articular fossa. The arrangement of these fibers had various directions, however most of fibers tended to run medio-laterally. The fiber bundles containing many elastic fibers ran into the retrodiscal area from the petrotympanic fissure. Although these fibers connected the most medial side of the disk with the medial side of the posterior wall of the articular fossa, they had many branches composing the retrodiscal area as stayed above. The fibers were very wavy, in spite of the protruded position of the disk. So these fibers were not considered to have a role in pulling back the disk in the retruded phase of the mouth closing. New findings as to the retrodiscal connective tissue were obtain in this research. They were different from Ree's description.

Cartilage, Articular↗

Connective tissue components of the normal and fibrotic liver. I. Structure, local distribution and metabolism of connective tissue components in the normal liver and changes in chronic liver diseases.

The first part of this review describes the chemistry, the occurrence and the metabolism of extracellular connective tissue components in the liver. The normal liver contains typical connective tissue proteins (collagens, structural glycoproteins and proteoglycans) not only in vessel walls, perivascular areas and in the capsule, but they occur also in small amounts in the parenchyma, mainly in the space of Disse along the sinusoidal walls. The "interstitial" collagens type I and III represent the major amount of collagen in the normal as well as in fibrotic liver, showing a relative increase of type III in fibrosis. Basement membrane collagens type IV and V as well as the cysteine-rich collagenous components "7 S collagen" and "short chain collagen" have been shown to occur in extracts prepared after limited pepsin digestion. In the normal liver, basement membrane collagen can hardly be detected within the parenchyma by immunofluorescence microscopy; increased occurrence, however, can be shown along the sinusoids even in early stages of chronic liver diseases. The glycoprotein fibronectin was shown to be distributed very similarly to collagens type I and III, whereas the basement membrane specific glycoprotein laminin is restricted to vessel walls and the epithelial layer of bile ductuli in the normal liver but is also found in the parenchyma in fibrosis. Occurrence of proteoglycans is increased in fibrosis: a change in the composition of glycosaminoglycans from mainly heparan sulfate in the normal to dermatan- and chondroitin sulfate in the fibrotic liver was observed. It is not yet clear which cell type is mainly responsible for increased connective tissue synthesis in fibrosis. The occurrence of cells resembling smooth muscle cells ("myofibroblasts") in connective tissue septa of fibrotic livers and the fact that similar cells which actively synthesize collagen grow from explants of fibrotic livers may indicate the significance of this cell type in the process of liver fibrosis.

Basement Membrane↗

[Influence of female sex on the respiratory manifestations of connective tissue disease].

Connective tissue diseases predominating in females include disseminated lupus erythematosus, antiphospholipid syndrome, primary pulmonary hypertension, Sjögren's syndrome, and rheumatoid arthritis. Pulmonary involvement is not uncommon and clinical expression may be modified by pregnancy. In addition, a certain number of drugs used for their treatment have an effect on fertility and pregnancy. We review here these different aspects and female-specific diagnostic and therapeutic features of connective tissue diseases.

Anti-Inflammatory Agents↗

[Gastroenterologic aspects of connective tissue diseases].

The connective tissue disorders are a protean group of acquired diseases which have in common widespread immunologic and inflammatory alterations of connective tissue. The acquired connective tissue diseases generally include the following clinical entities: rheumatoid arthritis, systemic lupus erythematosus, polymyositis, polyarteritis nodosa, scleroderma, mixed connective tissue disease, Sjögren's and Behcet's sindromes. These entities have certain features in common which include sinovitis, pleuritis, myocarditis, endocarditis, pericarditis, peritonitis, vasculitis, myositis, changes in skin, alteration of connective tissue and nephritis. Gastrointestinal and hepatic involvement in connective tissue disorders are not the most important features, nevertheless appear almost regularly. Anorexia, nausea, vomiting, abdominal pain, malabsorption may affect patients suffering by rheumatoid arthritis, systemic lupus erythematosus and other collagenophaties. In some cases mesenteric vasculitis may cause intestinal ischemia which may result in bowel infarction, mucosal ulceration, hemorrhage, perforation. After an extensive review of the existing literature the Authors make an accurate evaluation of gastrointestinal and hepatic alterations in connective tissue diseases.

Arthritis, Rheumatoid↗

Coronary spastic angina in patients with connective tissue disease.

BACKGROUND: Connective tissue disease, which is an inflammatory condition represented by C-reactive protein (CRP), is a risk factor for ischemic heart disease. The aim of the present study was to examine if there is a relationship between connective tissue disease and coronary spastic angina, and whether the inflammatory condition was associated with ischemic heart disease, even in patients with connective tissue disease. METHODS AND RESULTS: The study group comprised 73 consecutive patients with connective tissue disease who were admitted to the Department of Cardiovascular Medicine between April 2000 and March 2003. Of the 73 patients, 38 (19 men, 19 women) were diagnosed as having an ischemic heart disease (7 patients acute coronary syndrome, 19 patients coronary spastic angina, 12 patients stable exertional angina). In the present study, 19 (50.0%) of the 38 patients of ischemic heart disease were diagnosed as having coronary spastic angina. In the same study period, 151 (38.7%) of 390 patients with ischemic heart disease (without connective tissue disease) were diagnosed as having coronary spastic angina. The frequency of the patients with coronary spastic angina tended to be higher in patients with connective tissue disease than in patients without connective tissue disease. Among the study patients, serum CRP concentrations (mg/dl) were higher in patients with acute coronary syndrome (1.50 +/- 1.19, n=7) and those with coronary spastic angina (1.06 +/- 1.78, n=19) than in those with non-ischemia (0.35 +/- 0.40, n=35, p<0.05). CONCLUSIONS: Coronary spastic angina is a frequent complication in patients with connective tissue disease and the inflammatory condition is associated with coronary spastic angina and unstable angina in patients with connective tissue disease.

Aged↗

Undifferentiated, overlapping, and mixed connective tissue diseases.

Undifferentiated connective tissue disease (UCTD) is a term used by many rheumatologists to define a group of diffuse connective tissue disorders that lack definitive characteristics of any particular well-defined disorder. Overlapping connective tissue disease is often used interchangeably with UCTD but they both refer to diseases that are in evolution before all the characteristic clinical and laboratory symptoms are manifested. However, the clinical features of some of the overlapping connective tissue diseases appear to be better defined. The classical one is mixed connective tissue disease, where features of systemic lupus erythematosus, progressive systemic sclerosis, and polymyositis may exist together with a positive anti-extractable nuclear antibody and high titers of anti-ribonuclear protein antibody. This review attempts to clarify the confusion between these terms. The problems in the clinical and laboratory diagnosis of common connective tissue diseases that coexist are addressed and treatment options discussed. The long-term implications of making a diagnosis of a definitive connective tissue disease before all the required criteria are met should be kept in mind because the patient may never develop the disease and yet be subjected to psychological, social, and economic hardships.

Humans↗