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PubMed1987

Smooth muscle-mediated connective tissue remodeling in pulmonary hypertension.

Abnormal accumulation of connective tissue in blood vessels contributes to alterations in vascular physiology associated with disease states such as hypertension and atherosclerosis. Elastin synthesis was studied in blood vessels from newborn calves with severe pulmonary hypertension induced by alveolar hypoxia in order to investigate the cellular stimuli that elicit changes in pulmonary arterial connective tissue production. A two- to fourfold increase in elastin production was observed in pulmonary artery tissue and medial smooth muscle cells from hypertensive calves. This stimulation of elastin production was accompanied by a corresponding increase in elastin messenger RNA consistent with regulation at the transcriptional level. Conditioned serum harvested from cultures of pulmonary artery smooth muscle cells isolated from hypertensive animals contained one or more low molecular weight elastogenic factors that stimulated the production of elastin in both fibroblasts and smooth muscle cells and altered the chemotactic responsiveness of fibroblasts to elastin peptides. These results suggest that connective tissue changes in the pulmonary vasculature in response to pulmonary hypertension are orchestrated by the medial smooth muscle cell through the generation of specific differentiation factors that alter both the secretory phenotype and responsive properties of surrounding cells.

Animals↗
PubMed1979

Adult human skin maintained in organ culture: I. The ultrastructure of the acellular compartment of connective tissue.

Collagenolytic enzymes are produced by cultured skin explants. During cultivation the acellular compartment of the dermal connective tissues is digested away. The ultrastructure of the connective tissue resorption has been studied in human skin maintained in organ culture for 2--10 weeks. The connective tissue changes are: (1) Collagen fibrils with normal axial periodicity but decreasing diameters. On cross sections these fibrils have irregular outlines, while the longitudinal sections show fibrils separated into thin bundles of filaments 40--80 A thick with preserved normal axial periodicity. (2) Cross-banded filamentous aggregations (CBFA) consisting of fine parallel filaments 25 A thick and without axial periodicity. The CBFA has 350 A thick bands at 525 A intervals. At the end of the cultivation, the CBFA are replaced by solitary filaments 25 A thick. (3) The elastic fibres show no marked changes of the amorphous matrix, while the fibrils disappear. The loss of collagen and elastic fibrils during cultivation of the skin gives direct evidence of connective tissue degradation. The described changes are discussed in relation to previous ultrastructural studies on connective tissue resorption of various tissues.

Adolescent↗
PubMedDate not supplied

Elevated serum interleukin-6 levels associated with active disease in systemic connective tissue disorders.

OBJECTIVE: It is well established that connective tissue diseases such as systemic lupus erythematosus (SLE) are associated with a weak or absent acute phase response, although elevated serum interleukin 6 levels have been described. In this study, we have sought to correlate serum levels of IL-6 with standard laboratory and clinical assessments of disease activity in two connective tissue diseases, namely SLE and systemic sclerosis (SSc), and, for comparative purposes, rheumatoid arthritis (RA). METHODS: Serum IL-6 levels were determined by bioassay and also, in some sera, by immunoradiometric assay. They were compared with two inflammatory parameters, serum C-reactive protein (CRP) and plasma viscosity (PV), and with appropriate clinical measurements in the various patient groups, including BILAG in SLE, the skin score in SSc, and the Ritchie index in RA. RESULTS: Serum IL-6 (SeIL-6) levels were elevated in active SLE, SSc, and RA. This was poorly correlated with the acute phase response in SLE and SSc, but there was a strong relationship of SeIL-6 to disease activity in these conditions. In SLE, the BILAG disease activity index correlated best with SeIL-6 levels while there was only a weak relationship between CRP and IL-6, and no relationship between CRP and disease activity. In SSc there was a relationship of disease activity to SeIL-6 but not between SeIL-6 and either CRP or PV. In a small RA group there was a much stronger relationship of SeIL-6 to CRP and PV, as has been previously described. CONCLUSION: The determination of SeIL-6 may be a useful indicator of disease activity in those patients groups, including SLE and SSc, in which a normal acute phase response by the liver is often lacking. The mechanism underlying this hepatic impairment requires further investigation, but is clearly not due to a failure to generate the appropriate cytokine signal. Excessive local or systemic production of IL-6 in connective tissue diseases could play an important pathogenic role in these conditions, for example through stimulating autoantibody synthesis.

Arthritis, Rheumatoid↗
PubMed1976

[Circadian rhythms in connective tissue].

A study of circadian rhythms in the connective tissue showed cell elements (particularly histiocytes) to be characterized by circadian rhythms of the metabolic processes. This is expressed in a distinct diurnal activity of the succinic dehydrogenase (SDH) and lactic dehydrogenase (LDH). In the processes of adaptation to the high altitude hypoxia the activity of SDH and LDH was higher than in control, but dynamics of the changes of their activity repeated the changes in control group. It is concluded that circadian rhythms of the metabolic processes in the connective tissue were sufficiently stable: no visible changes were observed during adaptation to high altitudes.

Adaptation, Physiological↗
PubMed2003

Cell-matrix and cell-cell contacts of myofibroblasts: role in connective tissue remodeling.

It is presently accepted that fibroblast/myofibroblast modulation represents a crucial step in granulation tissue contraction and in the production of the connective tissue deformations typical of fibrocontractive diseases. In addition to synthesizing extracellular matrix (ECM) components, myofibroblasts can develop tensile force through the neoformation of alpha-smooth muscle actin (alpha-SMA) containing cytoplasmic stress fibers. Tension has been shown to be a crucial regulator of connective tissue remodeling. In order to coordinate tension distribution within connective tissue, cell-matrix and cell-cell contacts appear essential. This review addresses the formation, molecular structure and function of such structures that are characterized by their association with intracytoplasmic actin filaments. Actin associated cell-matrix adhesions appear to provide the interface between ECM components and intracellular stress fibers, thus contributing to the transmission of force to the substrate and to the detection of stress level in the matrix. Cell-cell adherens junctions appear to synchronize myofibroblast contractile activity. Further studies investigating the functions of these structures will be important for the understanding of the mechanisms of granulation tissue evolution and for the planification of strategies in view of influencing connective tissue deformations.

Actins↗
PubMed2005

Epidemiological study of patients with connective tissue diseases in Brazil.

To study the prevalence of connective tissue disorders and identify the epidemiological profile of the population from the northern and northeastern regions of Brazil. All patients admitted to the general medical ward at Getulio Vargas Hospital were screened through history and physical examination for the existence of known, suspected or possible connective tissue disorder. A total of 120 patients were enrolled in the study - 61 (50.8%) with systemic lupus erythematosus (SLE), 41 (34.2%) with rheumatoid arthritis (RA), 16 (13.3%) with systemic sclerosis (SS), one (0.8%) with mixed connective tissue disease (MCTD) and one (0.8%) with polymyositis (PM). Women accounted for (104) 86.7% of the participants and (83) 70.9% were non-Caucasians. The mean age was 36.8 years. Alopecia was the most frequent symptom (55/46.6%), followed by other cutaneous lesions (50/42.4%), dyspnea (47/39.8%) and chest pain (39/33.0%). The most frequent rheumatologic disorder encountered in our hospital-based study population was systemic lupus erythematosus, which is contrary to findings of the majority of studies performed in this country.

Adult↗
PubMed1989

Heterogeneity of ribosomal autoantibodies from human, murine and canine connective tissue diseases.

Antiribosomal auto-antibodies (anti-Rib.Ab) have been studied in connective tissue diseases (human, dog and mouse) by immunoblotting after one-dimensional (1D) or two-dimensional (2D) gel electrophoresis of rat ribosomes. Anti-Rib.Ab could be found in systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and other connective tissue diseases (progressive systemic sclerosis, PSS; Sjögren syndrome, SjS; mixed connective tissue disease, MCTD; and dermatomyositis, DM with the frequencies 41.7%, 54.6% and 33%, respectively. Immunoblotting after 1D gel electrophoresis showed the great heterogeneity of ribosomal proteins recognized by the anti-Rib.Ab. In the SLE, however, the most frequent antibodies stained bands of the 40S subunit: 30 kDa (34% of positive sera), 19.5 kDa (24.5%) and 43 kDa (17%). In RA, the 25-kDa band of the 60S subunit was the most common (54% of positive sera). In the other human connective tissue diseases, there was no particular predominance. In the MRL/1, anti-Rib.Ab were very frequent (92.6%). The 43-kDa band of the 40S subunit was found in 100% of positive sera. Seventeen out of nineteen dogs with SLE gave positive results on immunoblot, and all of them stained the 43-kDa band of the 40S subunit. 2D gel electrophoresis gave identification of Po, L7, L5, Sb, S19, S13 and L2 proteins in SLE, S3 and SjS, L35a and L37a in RA, and L7, S6 and/or L7a in MRL/1.

Animals↗
PubMed1982

Relationships between the arteries and veins and the connective tissue system in the human orbit.

The arteries and veins in the apical region of the orbit occupy different areas. Furthermore, there is a difference in their relationships to the connective tissue system. In this part of the orbit, where only a few connective tissue septa are present, the arteries are mainly concentrated in the inner-space. The veins, on the other hand, are predominantly found peripherally, outside the muscle cone. The arteries are surrounded by adipose tissue. They are only in contact with connective tissue fibres when perforating the septa on their way to the outer regions of the inner-space. A small number of vessels, the posterior ciliary arteries and the central artery of the retina, keep their central position, grouped around the optic nerve. The conduct of this group of arteries in respect to the connective tissue is somewhat different than that of the other arteries. The ciliary arteries and the central retinal artery have varying contacts with the optic sheath. In contrast to the arteries, which in general lack firm connections with fibrous connective tissue, the major veins are encased in the tight connective tissue of the orbital fissures, or enveloped in connective tissue septa. For the smaller veins, these fibrous relationships are usually less intimate and occasionally disrupted. More extensive discussion and conclusions will be given in the following article. This will deal with the rest of the retrobulbar part of the orbit.

Adult↗
PubMed1996

Undifferentiated systemic connective tissue disease-"overlap' in Zimbabwe.

OBJECTIVE: To define the clinical characteristics of the overlapping, undifferentiated systemic connective tissue disease in one of the tropical African countries. DESIGN: A descriptive retrospective study of records of patients registered on a special rheumatology clinic between 1989 and 1994. SETTING: Harare Central Hospital Rheumatology Clinic, Zimbabwe. SUBJECTS: All registered patients with systemic connective tissue diseases. MAIN OUTCOME MEASURES: Numbers of patients, laboratory and clinical features of undifferentiated overlapping connective tissue disease. RESULTS: The distribution for those who satisfied internationally accepted criteria for classification/diagnosis were: 48(52.8pc) rheumatoid arthritis (RA), 17(18.7pc) systemic lupus erythematosus (SLE), 10(11pc) juvenile chronic arthritis (JCA), four (4.4pc) polymyositis/dermatomyositis (PMD) and 11 (12.1pc) overlapping connective tissue disease (overlap) and one unclassified disease. No pure progressive systemic (PSS) was registered. Among the overlap patients, five had SLE-RA, three SLE-PSS and one each for SLE-RA-PSS, RA-PSS and SLE-PDM overlapping clinical features respectively. In two patients with SLE-PSS, the criteria of each of the individual connective tissue disease were satisfied. Similarly, in one patient with SLE-RA and another with RA-PSS features, the criteria of individual disease were also satisfied. CONCLUSION: In undifferentiated overlapping connective tissue diseases-overlaps occur in tropical Africa, the SLE-RA overlapping features predominate and are moderately severe diseases.

Connective Tissue Diseases↗
PubMedDate not supplied

Effect of epidermal growth factor on cell proliferation in normal and wounded connective tissue.

Epidermal growth factor has been previously shown to stimulate connective tissue repair in the perforated rat mesentery. The mechanism by which epidermal growth factor accelerates closure of mesenteric perforations has not been established, but epidermal growth factor may stimulate mitosis, contraction, migration, or angiogenesis. In the present investigation, the effect of epidermal growth factor on connective tissue cell proliferation was studied during the initial phase of repair of mesenteric perforations and in unwounded mesentery. Laparotomies were performed on Sprague-Dawley rats, and standardized perforations were made with a scalpel in the center of the mesenteric "windows," leaving every second window as an internal control. Twice daily for 4 consecutive days, beginning on the day of surgery, the animals received by intraperitoneal injection either 10 microg of epidermal growth factor dissolved in phosphate-buffered saline solution or phosphate-buffered saline solution alone. Cell proliferation was measured by either mitotic index of fibroblasts and mesothelial cells or DNA content of individual fibroblast cell nuclei in the wound area or in unperforated control windows. Laparotomy alone was found to enhance proliferation during the early postoperative period, as shown by increased numbers of S + G2 fibroblasts and a greater mitotic index. Epidermal growth factor treatment increased the mitotic index in perforated windows on the third postoperative day, compared with controls treated with phosphate-buffered saline solution, but did not significantly increase either the number of S + G2 fibroblasts or the mitotic index in unwounded tissue. Also, the proliferative response after epidermal growth factor treatment was significantly higher in wounded tissue. This study shows that epidermal growth factor stimulates proliferation of connective tissue cells in wounded but not unwounded tissue, and such enhancement of fibroblast proliferation might be of importance in epidermal growth factor-stimulated connective tissue repair.

Journal Article↗
PubMed2004

Silicone breast implants and connective tissue disease: an updated review of the epidemiologic evidence.

Numerous meta-analyses, weight-of-the-evidence, and critical reviews have summarized data from case-control and cohort studies, published through 1999, which have been conducted to evaluate the potential association between cosmetic silicone breast implants and the occurrence of well-defined connective tissue diseases, as well as a hypothesized new atypical disease, which does not fulfill established diagnostic criteria for any known connective tissue disease. These reviews have unanimously concluded that there is no evidence of an association between breast implants and any of the traditional connective tissue diseases evaluated individually or combined or atypical connective tissue disease. We have performed an updated review of the results of epidemiologic studies published since 1999. Two long-term follow-up studies of women with breast implants in Denmark and a retrospective cohort study in Australia found no excess of definite connective tissue disease, including rheumatoid arthritis, systemic sclerosis, systemic lupus erythematosus and Sjogren's syndrome, among women with cosmetic breast implants compared with breast reduction or other plastic surgery controls or women in the general population. No consistent evidence was observed of increased risk of definite connective tissue disease in women with extracapsular ruptures in 2 studies which evaluated risk by rupture status among women with cosmetic breast implants. The results of several studies provide no evidence of a higher frequency of undefined connective tissue disease among women with cosmetic breast implants or of a rheumatic symptom profile unique to these women and/or indicative of a specific atypical connective tissue disease. In conclusion, the most recent epidemiologic investigations have been remarkably consistent with earlier epidemiologic studies in finding no evidence of an excess of any individual connective tissue disease or all connective tissue diseases combined, including both established and atypical or undefined connective tissue disease, among women with cosmetic silicone breast implants. Thus, the conclusions reached in earlier independent reviews have not changed based on data published during the subsequent years.

Australia↗
PubMed1990

[Experimental studies on healing process of plication technique at postdiscal connective tissue of TMJ in Macaca fuscata].

The purpose of this study is to evaluate the healing process following application of the plication technique at the postdiscal connective tissue of the temporomandibular joint (TMJ). Female monkeys (Macaca fuscata) approximately eight years old were subjected to bilateral TMJ operations. The plication technique was performed in the left joint of each animal. In the right TMJ, the only operation performed was the exposure of the upper joint cavity. Results. 1) No synovial cells occurred on any upper surfaces of postdiscal connective tissue in left, first-week, postsurgical specimens. No synovial cells were observed in the area from the lateral to the middle upper surface of postdiscal connective tissues in specimens taken from the control side. Synovial cells gradually regenerated from the outside and, by the fourth postsurgical week, all of them had recovered in specimens from both sides. 2) During the early period, fibrin precipitation, round cell infiltration, fibroblast proliferation, and vascularization occurred in the plicated region. But these symptoms gradually decreased; and, by the twenty-fourth postsurgical week, collagen fibers surrounded the sutures. In the upper cavity, sutures were covered by newly proliferated connective tissue four weeks after surgery. The giant cells that proliferated around sutures in the fourth week increased gradually. 3) From the first postsurgical week, connective tissue proliferated in the lateral and middle parts of the superior postdiscal connective tissue in the right joint. Similar proliferation occurred in the left joint in the inner side of plicated region. Round cell infiltration took place in these connective tissue in the early period but gradually decreased. As this occurred, numbers of fat cells increased. No significant difference was noticed between proliferation in the right and left joints. No adhesion to the synovium in the glenoid fossa was observed. 4) In the first postsurgical week, connective tissue proliferated bilaterally from the posterior edges of both the glenoid fossa and the postdiscal tissue. In the second and fourth postsurgical weeks, connective tissue proliferation formed a fold narrowing the upper joint cavity. 5) Synovial cells were absent from the lateral to the middle region of both glenoid fossa from the first postsurgical week. Regeneration took place from the outside, and all synovial cells had recovered by the fourth postsurgical week. Disappearance of synovial cells was more extensive in the left than in the right glenoid fossa. 6) Round cell infiltration, vascularization, collagen fiber hyalinization, and hyperplasia of the fibrous covering occurred in the lateral part of the fibrous covering of the glenoid fossa but gradually decreased.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1994

Connective tissue tumors in patients with cutaneous melanoma.

BACKGROUND: A possible relation between cutaneous melanoma and connective tissue tumors has been described. OBJECTIVE: After the observation that a group of our patients had both cutaneous melanoma and a soft tissue sarcoma, we elected to review this formally. Eleven patients with both diagnoses were identified and are described. METHODS: A computer search through the Medical Records Department and the Tumor Registry of the Massachusetts General Hospital identified seven men and four women with the diagnoses of melanoma and malignant bone or soft tissue sarcoma. The medical records and pathology specimens of all tumors were reviewed. RESULTS: In three patients, the two tumors were diagnosed within 1 year of each other, in seven, the diagnosis of melanoma was made first, and in one, melanoma was diagnosed after the connective tissue lesion. The interval between the two diagnoses ranged up to 13 years. Although the locations and types of melanoma were typical, some of the connective tissue tumors were unusual; there were two sacral chordomas. In two instances, the melanoma and connective tissue tumor were anatomically close; the sarcoma developed at the edge of the resection of the prior melanoma in one patient. None of the tumors developed in previously irradiated tissues, and in no instance did the second tumor appear to be caused by the therapy received for the first. None of the patients had a family history of melanoma. Four patients had other cancers in addition to the melanoma and connective tissue tumor. CONCLUSION: Although these patients were seen in a referral center, it is our impression (based on the total number of patients with connective tissue tumors seen and the incidence of melanoma in the general population) that observing 11 patients with both types of tumors is greater than would be expected by chance.

Adult↗
PubMed1989

Epithelial dendritic cells and connective tissue macrophages in oral carcinogenesis and the effects of systemic Corynebacterium parvum.

Epithelial dendritic cells (EDC) and connective tissue macrophages were examined during the induction and growth of oral squamous cell carcinomas in Sprague-Dawley rats treated with the carcinogen 4-nitroquinoline N-oxide (4NQO) and the immune potentiator Corynebacterium parvum. Splenomegaly was induced in all animals receiving C. parvum. Acetone-fixed frozen sections of the palate and tongue were stained using an indirect immunoperoxidase technique and monoclonal antibodies to rat Ia (MRC OX-6) and macrophage subpopulations (ED1, ED2, ED3). EDC were predominantly Ia+, ED1-, ED2- and ED3-. The lamina propria contained Ia+, ED1+ and ED2+ cells; ED3-reactive cells were rare. ED2+ cells predominated in the interstitial connective tissue of deeper muscle. In the non-invasive tissues, the number of positive cells (Ia+EDC and connective tissue Ia+, ED1+ and ED3+ cells) increased significantly throughout the experimental period (0-9 months), were significantly more prevalent in the test tissues (4NQO, 4NQO + C.parvum, C.parvum) compared to untreated controls and, at 9 months, the carcinogen-treated rats (4NQO, 4NQO + C.parvum) had significantly more Ia+ EDC and connective tissue Ia+ cells than C.parvum controls. Irrespective of the marker under study, there were no significant differences between rats treated with 4NQO or 4NQO + C.parvum at any time during the experimental period. Similarly, intra-epithelial Ia+ and ED1+ cells increased significantly throughout the experimental period in all test groups compared to untreated controls, but no significant differences were evident between carcinogen-treated animals (4NQO, 4NQO + C.parvum) and C.parvum controls. Significant positive correlations between connective tissue Ia+ and ED1+ cells and also intra-epithelial Ia+ and ED1+ cells were present in all experimental groups; connective tissue ED2+ and ED3+ cell numbers did not correlate with any of the other phenotypes and intra-epithelial ED2+ and ED3+ cells were rare/absent. Palatal and/or lingual tumours developed in 80% of carcinogen-treated rats by 9 months and the tumour incidence was similar in rats treated with either 4NQO or 4NQO + C.parvum. There were no significant differences in the number of Ia+ EDC between the infiltrating and the non-invasive overlying epithelium of the lingual carcinomas and the non-invasive lingual epithelium treated with either 4NQO or 4NQO + C.parvum.(ABSTRACT TRUNCATED AT 400 WORDS)

4-Nitroquinoline-1-oxide↗
PubMed2004

Tissue response to a new methacrylate-based root canal sealer: preliminary observations in the subcutaneous connective tissue of rats.

Silicone tubes filled with EndoRez, a methacrylate-based root canal sealer, were implanted in the subcutaneous connective tissue of the rat. Solid, silicone rods of the same size as the tubes also were implanted and used as negative controls. The tissue reaction to test and control materials was histologically studied and analyzed by elemental electron-microprobe analysis. After 10, 30, 90, and 120 days of implantation, different grades of tissue reaction to the tested materials were recorded. A granulomatous tissue containing numerous polymorphonuclear leukocytes, lymphocytes, and plasmocytes, as well as macrophages and foreign-body giant cells with engulfed material in their cytoplasm, was initially observed in contact with EndoRez. Fibroblasts and newly formed vessels also were observed. This cellular profile persisted after 30 days. The severity of the reaction decreased with time, and connective tissue healing was observed at the 120-day observation period, even though some specimens exhibited a slight, persistent, inflammatory cell infiltration. The electron-microprobe analysis of the tissues revealed the presence of heavy components of EndoRez in all observation periods. In contact with the controls, there was an initially slight concentration of inflammatory cells. This reaction rapidly subsided after 30 days, and a fibrous connective tissue encapsulation, free of inflammatory cells, could be observed at the 90- and 120-day observation periods.

Animals↗
PubMed2005

Analysis of shedding of 3 beta-herpesviruses in saliva from patients with connective tissue diseases.

BACKGROUND: Whether an association exists between infection with beta -herpesviruses and connective tissue diseases remains unclear, as are the mechanisms for the regulation of these infections in the salivary glands. METHODS: Human herpesvirus (HHV)-7 was isolated and viral DNA was quantified by real-time polymerase chain reaction (PCR) in serially collected saliva samples, to determine whether viral load correlated with infectivity. Then, to examine the role played by beta -herpesviruses in connective tissue diseases, cytomegalovirus, HHV-6, and HHV-7 DNA loads were examined by real-time PCR in serially collected saliva samples from 21 patients with connective tissue diseases. RESULTS: Although subjects with frequent HHV-7 shedding were more likely to have a high viral load than were other subjects, high viral loads were detected in saliva samples from a portion of the subjects with low viral shedding rates. No significant difference between the quantity of HHV-7 DNA in saliva samples from which active virus was isolated and that amplified from samples without detectable virus was observed. Patients with adult-onset Still disease consistently had high HHV-7 DNA loads, in contrast to patients with other connective tissue diseases (P=.0003) and healthy adults (P=.0224). The mean HHV-6 (P=.012) and HHV-7 (P<.0001) DNA loads in patients with connective tissue diseases were lower than those in healthy adults. CONCLUSION: These data suggest that a number of host factors in patients with adult-onset Still disease may function to accelerate HHV-7 replication in the salivary glands.

Adult↗