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PubMed1991

Connective tissue content of fibrolamellar carcinoma and other human liver tumors.

The connective tissue content of four different human liver tumors (Fibrolamellar carcinoma, FLC; hepatocellular carcinoma, HCC; focal nodular hyerplasia, FNH and hepatocellular adenoma, HCA) was investigated by computer aided morphometry. A significantly higher connective tissue content was found in FNH and FLC as compared to HCA and HCC. The distribution of the connective tissue was homogeneous in the cases of FNH, HCA and HCC, while a highly unhomogeneous distribution was observed in FLC cases.

Adolescent↗
PubMed1982

[Evolution of connective tissue diseases with anti-ribonucleoprotein antibodies (in 28 patients) (author's transl)].

Follow-up of 28 patients with connective tissue diseases with anti-RNP antibodies revealed that the disease had followed a benign course in 19 cases and a more severe course (including one fatal outcome) in 9 cases. Severe symptoms were mainly renal, neurological, psychic, and articular in nature. The association of anti-DNA antibodies and or low blood complement levels was confirmed as being of poor prognostic significance. Correlating the clinical picture with the severity of the cases demonstrated one case of the severe form in 8 minor connective tissue diseases (arthralgia, Raynaud's syndrome, swollen fingers), three severe forms (including one death) in 9 cases of mixed diseases, and 5 severe forms in the 11 patients with isolated connective tissue disease. Minor connective tissue syndromes retain an overall favourable prognosis, but they may become severe. The poor prognosis of the juvenile forms and those related to scleroderma also has to be emphasised.

Adolescent↗
PubMed1991

Connective tissue content of fibrolamellar carcinoma and other human liver tumors.

The connective tissue content of four different human liver tumors (Fibrolamellar carcinoma, FLC; hepatocellular carcinoma, HCC; focal nodular hyperplasia, FNH and hepatocellular adenoma, HCA) was investigated by computer aided morphometry. A significantly higher connective tissue content was found in FNH and FLC as compared to HCA and HCC. The distribution of the connective tissue was homogeneous in the cases of FNH, HCA and HCC, while a highly unhomogeneous distribution was observed in FLC cases.

Adolescent↗
PubMed1978

Incidence and significance of different types of connective tissue antibodies in adult and pediatric gastroenterological disorders.

The incidence of connective tissue antibodies was assessed in 3,000 adults and in 388 pediatric patients with gastroenterological disorders. Following a previous classification, connective tissue antibodies were distinguished in 5 different types, R1 and R2 reacting with reticulin components, KC with Kupffer cells, AC and Rs with intra- and extracellular mesenchymal antigens. R1 predominated in children and was observed only in patients with malabsorption; the great majority of them had celiac disease and an abnormal small bowel mucosa. Ac was rarely seen in children and occurred in several unrelated gastrointestinal diseases of the adult; its incidence, however, was significantly higher in disorders with idiopathic and secondary malabsorption. R2, KC and Rs were seen only occasionally in unrelated gastroenterological disorders without malabsorption. R1, therefore, seems to be strongly suggestive of a malabsorption syndrome with abnormal small bowel mucosa and AC is a nonspecific reaction occuring predominantly in primary and secondary malabsorption; the other connective tissue antibodies have no clinical significance in gastroenterological disorders.

Adult↗
PubMed1998

Risk of connective tissue disease and related disorders among women with breast implants: a nation-wide retrospective cohort study in Sweden.

OBJECTIVE: To examine the relation between connective tissue disease and related conditions and breast implants. DESIGN: Retrospective cohort study of all women in the Swedish national inpatient registry who underwent breast augmentation surgery with artificial implants during 1964-93, compared with women who underwent breast reduction surgery during the same period. SETTING: Sweden. SUBJECTS: 7442 women with implants for cosmetic reasons or for reconstruction after breast cancer surgery and 3353 women with breast reduction surgery. MAIN OUTCOME MEASURES: Subsequent hospitalisation for definite connective tissue diseases (rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, dermatomyositis, and Sjögren's syndrome) or related disorders. RESULTS: 29 women with implants were hospitalised for definite connective tissue disease compared with 25.5 expected based on general population rates (standardised hospitalisation ratio 1.1 (95% confidence interval 0.8 to 1.6)). There were no diagnoses of systemic sclerosis, and no significant excess in risk for polymyalgia rheumatica, fibromyalgia, and several related disorders. Among women who underwent breast reduction surgery, 14 were hospitalised for definite connective tissue disease compared with 10.5 expected (standardised hospitalisation ratio 1.3 (0.7 to 2.2)). Compared with the breast reduction group, women with breast implants showed a slight reduction for all definite connective tissue disease (relative risk 0.8 (95% confidence interval 0.5 to 1.4)). CONCLUSIONS: This large nationwide cohort study shows no evidence of association between breast implants and connective tissue disease.

Adult↗
PubMed2004

Connective tissue disorders with spontaneous spinal cerebrospinal fluid leaks and intracranial hypotension: a prospective study.

OBJECTIVE: Intracranial hypotension attributable to a spontaneous spinal cerebrospinal fluid (CSF) leak is an increasingly recognized cause of postural headaches. The cause of these leaks is poorly understood, but it is likely multifactorial and may involve a primary connective tissue disorder. We undertook a study to estimate the contribution of systemic connective tissue disorders to the development of spontaneous spinal CSF leaks. METHODS: We examined a group of 18 consecutive patients with spontaneous spinal CSF leaks for features of a connective tissue disorder. RESULTS: The mean age of the 15 female patients and 3 male patients was 38 years (range, 22-55 yr). Seven patients (38%) demonstrated stigmata of a systemic connective tissue disorder, and three distinct types of disorders could be identified, as follows. 1) The association of spontaneous spinal CSF leaks and minor skeletal features of Marfan syndrome was noted for three patients. 2) Ehlers-Danlos syndrome Type II was noted for two patients. 3) Joint hypermobility associated with marked attenuation of the dorsal muscular fascia, precluding proper wound closure, was noted for two patients. In addition, isolated small-joint hypermobility was observed for five patients (28%). Slit-lamp ocular examinations, echocardiographic evaluations, histopathological examinations of skin biopsy specimens, and renal scanning did not reveal any other features of a systemic connective tissue disorder. CONCLUSION: Findings suggesting connective tissue disorders are common among patients with spontaneous spinal CSF leaks, and manifestations may be subtle. A variety of disorders can be identified, probably reflecting genetic heterogeneity. Problems with wound healing may occur as a result of the systemic nature of the underlying connective tissue disorder.

Adult↗
PubMed1986

Changes in the connective tissue and decrease in the number of mast cells in the testes of men with alcoholic and non-alcoholic cirrhosis.

The testicular connective tissue of patients with alcoholic and non-alcoholic cirrhosis was studied by Picrosirius staining for collagen fibres and electron microscopy, and then compared with the connective tissue of normal testes. Under polarized light, the interstitial connective tissue in the testes of patients with alcoholic and non-alcoholic cirrhosis exhibited a green birefringence which did not appear in normal testes, and the orange birefringence characteristic of the tunica propria in the testes of both cirrhotic and normal males was less developed in cirrhosis. This suggests that a connective tissue, consisting of smaller and less ordered collagen fibre bundles than those in the tunica propria is formed in the testicular interstitium of cirrhotic males, and the collagen fibre bundles of the tunica propria are less developed than in normal testes. The appearance of connective tissue was associated with a decrease in the number of mast cells in the testes of cirrhotic males suggesting the involvement of mast cells in the synthesis, packing, and organization of collagen fibres. The cause of the decrease in mast cell numbers may be related to hormone alterations, in particular testosterone deficiency.

Adult↗
PubMed1991

Pentosome--a new connective tissue component--is a subunit of amyloid P.

A new minute connective tissue structure, referred to as "pentosome", has been investigated by electron microscopy and its nature has been examined by immunoperoxidase tests. Pentosomes are 3.5-nm wide, particulate structures that have been observed in the posterior chamber of the eye, the connective tissue spaces of the mouse foot-pad and the matrix of the mouse EHS tumor. They are usually found in the vicinity of microfibrils whether they are free or associated with elastic fibers. They tend to be organized into groups forming a three-dimensional semi-crystalline lattice at 10-nm intervals, but are connected by fine filaments. At high magnification, pentosomes appear as hollow structures composed of two parallel pentagons, which respectively measure 2.7 and 3.5 nm, and are held together by a cross-bar. A series of immunoperoxidase tests has only shown antigenicity against a serum protein, the amyloid P component. However, pentosomes are only about one-third the size of the 8.5-nm wide, disk-like segments of the amyloid P molecule. Since they could be subunits of these molecules, such subunits were prepared and compared with pentosomes; they appeared to be identical. It is concluded that the pentosomes found in connective tissue are AP subunits.

Animals↗
PubMed1988

Protein-losing enteropathy and mixed connective-tissue disease.

A case of a person with a mixed connective-tissue disease, who subsequently developed protein-losing enteropathy with a partial response to prednisolone therapy, is presented. Protein-losing enteropathy has been reported in several patients with systemic lupus erythematosus but not in patients with mixed connective-tissue disease. This case broadens the association of protein-losing enteropathy with autoimmune diseases and suggests that the diagnosis should be considered in patients with mixed connective-tissue disease who have hypoalbuminaemia.

Adult↗
PubMed2002

Keratinocytes inhibit expression of connective tissue growth factor in fibroblasts in vitro by an interleukin-1alpha-dependent mechanism.

The wound healing process concludes with downregulation of fibroblast activity. Clinical observations suggest that the regenerating epidermis suppresses this activity. An important regulator of fibroblast activity is the fibrogenic cytokine connective tissue growth factor. We hypothesized that epidermal keratinocytes may affect fibroblast activity via this cytokine. We demonstrate keratinocyte-mediated suppression of connective tissue growth factor at both the mRNA and protein levels by around 50% or more when fibroblasts were cultured in multiwell plates with keratinocyte cultures in accompanying semipermeable cell culture inserts, or stimulated by keratinocyte-conditioned media. Both basal and transforming-growth-factor-beta1-stimulated levels of connective tissue growth factor were inhibited. A 3 h coculture period with keratinocytes was sufficient to suppress connective tissue growth factor expression by fibroblasts, but the inhibition developed over a time period of around 16 h. The putative keratinocyte-derived factor(s) responsible for these effects was found to be soluble and stable. By analyzing cytokines secreted by keratinocytes we identified interleukin-1alpha as a potent inhibitor of connective tissue growth factor mRNA expression in fibroblasts. Involvement of this cytokine in keratinocyte-mediated connective tissue growth factor suppression was confirmed by using anti-interleukin-1alpha antibodies. Tumor necrosis factor alpha or prostaglandins did not appear to be involved. In conclusion, our results indicate that interleukin-1alpha secretion by keratinocytes provides a mechanism for the downregulation of connective tissue activity during the end-stage of wound healing, when epithelia coverage has developed over the wound area.

Coculture Techniques↗
PubMed1994

Multiple arteriovenous malformations in a man with a connective tissue disorder.

Multiple arteriovenous malformations in patients with connective tissue disorders are not reported. We describe a man with cutaneous, ligament/articular and vascular features suggestive of a connective tissue disorder and who also has multiple arteriovenous malformations resulting in a high output circulatory state. Chest pain due to arteriovenous malformations originating from subclavian vessels has caused considerable morbidity.

Adult↗
PubMed1977

Use of enzymolysis techniques in studying the mechanical properties of connective tissue components.

The optimum conditions for the selective removal of elastin from connective tissues are described. The process, elastolysis, consists of incubating small samples of connective tissue in buffered saline at ph=8.6 containing 300 microgram/me of a 50-50% mixture of elastase with trypsin inhibitor, for 5-6 hours at room temperature. This process, complimented with other processes for selective removal of lipids, or mucopolysaccharides, or collagen, enables one to examine the contribution of the various components of the connective tissue to its mechanical function. The elastolysis was tested with aortic, valvular and tendon tissues from human, bovine and canine species and it was found that in tensile stress experiments, collagen was unaffected while the low-stress contribution of elastin disappeared.

Animals↗
PubMed1996

The perforated mesentery of the rat: a novel model for the study of genuine connective tissue contraction.

The rat and mouse mesenteries consist of an array of thin, mesenchymally derived, connective tissue membranes. Perforations of rat membranes heal by closure within a week and the perforated rat mesentery has earlier been shown to be a very suitable model of true connective tissue repair. In the present study, the closure of perforations in the rat was studied by light and transmission electron microscopy as well as confocal microscopy after actin staining with phallacidin in order to better understand the cellular mechanisms of healing in this model. The healing of different sized mesenteric perforations was also quantitatively assessed and compared in rats and mice. Closure occurred rapidly between Days 5 and 7 in rats, the velocity of healing being dependent on the size of the wounds. During closure, fibroblasts close to the wound margin ultrastructurally showed long slender cytoplasmic processes that contained actin filaments as shown by fluorescence confocal microscopy. In mice, larger perforations of mesenteries decreased in size during the 3-week observation period, but very seldom closed completely. In conclusion, the data gathered now and earlier indicate that a contraction phenomenon is of major importance in the closure of rat mesenteric perforations. Until now, good models for genuine connective tissue contraction have been lacking and it is suggested that the perforated rat mesentery may be used as such a model system in the future. The finding that mouse mesenteric perforations normally do not heal will make comparative studies intriguing, but it also indicates basic differences between rats and mice with respect to connective tissue repair mechanisms.

Actins↗
PubMed1995

In the biosynthesis of N-glycans in connective tissue of the snail Lymnaea stagnalis of incorporation GlcNAc by beta 2GlcNAc-transferase I is an essential prerequisite for the action of beta 2GlcNAc-transferase II and beta 2Xyl-transferase.

Using a series of relevant substrates, connective tissue of the snail Lymnaea stagnalis was shown to contain beta 1-2 xylosyltransferase (beta 2Xyl-T), beta 1-2 N-acetylglucosaminyltransferase I (beta 2GlcNAc-T I), and beta 1-2 N-acetylglucosaminyltransferase II (beta 2GlcNAc-T II) activities. These enzymes are probably involved in the biosynthesis of the N-linked carbohydrate chains, like those present in hemocyanin. The products formed by incubation of GlcNAc beta 1-2Man alpha 1-6(GlcNAc beta 1-2Man alpha 1-3)Man beta 1-R [where R = -4GlcNAc beta 1-4GlcNAc or O-(CH2)7CH3] with UDP-Xyl and connective tissue microsomes have been purified and characterized by 1H-NMR spectroscopy in conjunction with methylation analysis to be GlcNAc beta 1-2Man alpha 1-6(GlcNAc beta 1-2Man alpha 1-3)(Xyl beta 1-2)Man beta 1-R. Substrate specificity studies focused on connective tissue beta 2Xyl-T show that the minimal structure requirements are fulfilled in GlcNAc beta 1-2Man alpha 1-3Man beta 1-O-(CH2)7CH3. The enzyme activity can therefore be characterized as UDP-Xyl:Glc-NAc beta 1-2Man alpha 1-3Man beta-R (Xyl to Man beta) beta 1-2 xylosyltransferase. In substrate-specificity studies directed to connective tissue beta 2GlcNAc-T I, it could be demonstrated that the enzyme is active towards acceptors having at the minimum a Man alpha 1-3Man beta-R sequence, and that introduction of a beta Xyl residue at C2 of beta Man totally abolishes the enzyme activity. Xylose-containing oligosaccharides are not acceptors for beta 2GlcNAc-T I. In combination with the substrate specificity of beta Xyl-T, this shows that in snail connective tissue beta 2GlcNAc-T I must act before beta 2Xyl-T. The connective tissue beta 2GlcNAc-T II activity follows the earlier established biosynthetic routes. Based on the substrate specificities of the various connective tissue glycosyltransferases known so far, and the structures isolated from L. stagnalis hemocyanin, a partial biosynthetic scheme for N-glycosylation in snail connective tissue is proposed.

Animals↗
PubMed2006

Bosentan therapy of pulmonary arterial hypertension in connective tissue diseases.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a life-threatening and debilitating complication of several connective tissue diseases. We aimed to evaluate the effects of long-term treatment with bosentan, an oral dual endothelin ET(A)/ET(B) receptor antagonist, in a cohort of patients with PAH related to connective tissue diseases. MATERIALS AND METHODS: In the present prospective, noncontrolled study, 13 patients (nine with systemic sclerosis, two with systemic lupus erythematosus, one with mixed connective tissue disease and one with overlap syndrome including scleroderma and myositis), mostly nonresponders to prostanoids therapy, were treated for 1 year with bosentan. Cardiac haemodynamics and the diagnosis of PAH were performed by Doppler ultrasound examination. Exercise capacity was assessed by 6-min walking test at baseline and at 3, 6 and 12 months of therapy. RESULTS: During bosentan treatment, progressive improvement of exercise capacity was observed. Walk distance increased in seven patients, remained unchanged in three and slightly decreased in three patients. A progressive significant decrease of right ventricular systolic pressure was also observed, whereas pulmonary artery mean pressure remained unchanged. Adverse effects related to bosentan (elevation of hepatic aminotransferases) were noted in two patients. CONCLUSION: Long-term treatment with bosentan was effective in improving exercise capacity and pulmonary haemodynamics in patients with PAH related to connective tissue diseases.

Administration, Oral↗
PubMed1975

Blood vessels and connective tissue in autotransplanted free muscle grafts of the cat.

After 2 weeks of denervation, whole leg muscles of adult cats were transplanted to intercostal spaces and removed at intervals from 5 days to 44 weeks after grafting. The connective tissue formation and capillary supply of the grafts were studied histologically and histochemically for connective tissue and ATPase. In addition, normal muscles, denervated muscles left in situ, and muscles transplanted without previous denervation were studied. During the denervation period of 2 weeks the capillary network increased slightly. During the first 6 weeks after grafting only a few, thick-walled, irregularly shaped capillaries were present in the grafts. At 8-12 weeks there was a pronounced increase in the vascular supply, coincident with reinnervation of the grafts, and after 40 weeks the capillary pattern appeared fairly normal. In the early stages a marked increase in perimysial and endomysial connective tissue took place. With increasing reinnervation a gradual disappearance of the endomysial connective tissue occurred and in the most mature grafts a minimal increase of perimysial connective tissue remained. In muscles transplanted without previous denervation, extensive fibrotic changes developed.

Animals↗
PubMed1995

The human optic nerve: fascicular organisation and connective tissue types along the extra-fascicular matrix.

Fibres in the mammalian optic nerve are arranged into fascicles between which there is an extra-fascicular matrix containing connective tissue, a feature similar to that found in association with fibres in peripheral nerves, but not otherwise found in the CNS. The relationship between these major features of the nerve architecture are not known. We have addressed this question by examining the fascicular organisation of the optic nerve and the distribution of connective tissue and specific collagen types in the human. We have also examined the spatial development of connective tissue in the human nerve to determine when and from where it originates. Fibres are grouped into fascicles at all locations along the nerve, except intracranially, close to the chiasm where this pattern is lost. Relatively large fascicular numbers are found directly behind the eye and in the region of the optic canal, but decline in the mid-orbital segment of the nerve. Connective tissue is present in the extra-fascicular matrix throughout the fasciculated segment, but in many cases it does not fully encircle fascicles. The proportion of matrix occupied by connective tissue is similar along the length of the nerve (approximately 60%). Within the matrix, collagen types I, III, IV, V and VI are present throughout fasciculated regions. Staining for types V and VI appeared relatively weak compared with that for the other types. Although the collagen types in the nerve are similar to those at the lamina cribrosa and in peripheral nerves, they did not appear to be differentially distributed as in regions of the PNS. Connective tissue enters the nerve at a number of wide-spread locations early in development, consistent with the notion that it enters the nerve with the blood supply. It is present within the matrix before it is established at the lamina cribrosa.

Aged↗