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Biomedical subjects

G Cetta

Publications and source records attributed to G Cetta.

At least 73 records · Page 4Linked to original sources
PubMed1989

Ehlers-Danlos syndrome type IV: a subset of patients distinguished by low serum levels of the amino-terminal propeptide of type III procollagen.

Serum levels of procollagen type III aminopropeptide (P-III-NP), a peptide released during conversion of type III procollagen to collagen, were abnormally low in six of 10 patients with Ehlers-Danlos syndrome (EDS) type IV (arterial-ecchymotic type) and low-normal in 4. The serum P-III-NP levels correlated with the amount of type III procollagen secreted by the patients' cultured fibroblasts. Serum P-III-NP determination is a simple test that identifies a major subgroup of patients with this life-threatening, dominantly inherited connective tissue disorder and may be especially helpful in making the diagnosis in children.

Adolescent↗
PubMed1989

Low levels of serum type III procollagen aminoterminal propeptide confirmed type III collagen deficiency in patients without typical clinical symptoms of Ehlers-Danlos type IV.

Biochemical analysis of skin samples revealed that the content of type III collagen was greatly reduced in several subjects with joint hypermobility, stretchability and bruisability of skin. When cultured dermal fibroblasts were found to secrete decreased amounts of type III procollagen into medium (about 30-45% the normal amount) and serum type III procollagen aminopropeptide levels were significantly lower than normal values (P less than 0.001). The abnormalities in type III procollagen are in keeping with Ehlers-Danlos type IV although the clinical findings in our patients are not normally associated with this disorder. The results illustrate the clinical heterogeneity of Ehlers-Danlos type IV and the importance of biochemical analysis, such as determination of type III procollagen aminopropeptide levels, to check type III collagen metabolism especially if there is no family history and if correct diagnosis is not reliable by clinical examination alone.

Child↗
PubMed1989

Relationship between changes in alveolar surfactant levels and lung defence mechanisms.

Pulmonary surfactant, besides its mechanical properties, is thought to be involved in lung defence mechanisms. We previously described that: (1) in healthy animals, surfactant synthesis stimulation with ambroxol was accompanied by alveolar macrophage activation and a shift of the alveolar elastase/antielastase balance towards increased antielastase activity, and (2) in bleomycin-treated rats alveolar phospholipidosis was obvious 14 days after drug administration, ambroxol protection reduced the phospholipid peak and the morphological apperance of lung fibrosis at the 14th day of the experiment. The present study found that: (1) in healthy rats, the ambroxol-induced increase of alveolar antielastase activity did not appear due to reactivation of alpha 1-antitrypsin normally oxidized in the alveolar milieu; (2) in bleomycin-induced pulmonary fibrosis, ambroxol protection reduced total long collagen content at day 28, and (3) in paraquat-induced pulmonary fibrosis, alveolar phospholipids were markedly reduced throughout the 21 days of the experiment. On increasing the dose of paraquat, ambroxol protection significantly reduced the animals' death rate.

Ambroxol↗
PubMed1989

Biochemical, morphological and stereological study of the dermis in three members of a large family with type IV Ehlers-Danlos syndrome.

Biochemical, morphological and stereological studies were carried out on dermal biopsies obtained from three members of a large family with a positive clinical history of type IV Ehlers-Danlos syndrome. Ultrastructural analysis showed that fibroblasts from two affected individuals presented abnormally dilated rough endoplasmic reticulum cisternae engorged by microfilamentous material. When cultured, fibroblasts from two affected individuals synthesized and secreted normal amounts of type I procollagen, but only a very low percentage of type III procollagen was secreted. Cellular retention of type III procollagen was confirmed by immunofluorescence. Also the secretion of fibronectin appeared delayed. Stereological analysis carried out on semithin sections of dermis by the point counting method showed that the relative volume of collagen fibers was decreased in the reticular dermis and the relative volume of elastin fibers was increased mainly in the upper layer of reticular dermis, in comparison to normal controls (P less than 0.01). Collagen fiber sizes were significantly (P less than 0.01) reduced in all dermis layers. No alterations were seen in the dermis and in cultured fibroblasts from the clinically normal individual.

Adolescent↗
PubMed1988

Asymmetric Marfan syndrome.

We describe a girl with Marfan syndrome in whom the clinical expression of the disease was much more evident on the left side of the body.

Child, Preschool↗
PubMed1988

Type I procollagen in the severe non-lethal form of osteogenesis imperfecta. Defective pro-alpha 1(I) chains in a patient with abnormal proteoglycan metabolism and mineral deposits in the dermis.

We have screened type I procollagen synthesized in vitro by skin fibroblasts from several patients with the severe non-lethal form of osteogenesis imperfecta. Cells from one patient synthesized and secreted both normal and a larger amount of abnormal type I procollagen. The abnormal alpha chains are larger in size due to post-translational overmodifications involving the whole triple helical domain. Abnormal collagen heterotrimers had a melting temperature 2.5 degrees-3 degrees C lower than normal ones or from controls. Chemical analysis of collagen in the medium showed a greater degree of both lysyl hydroxylation and hydroxylysyl glycosylation, the major increase in molecular mass of overmodified alpha chains being due to the higher hydroxylysine-bound hexose content. The proband's cells modify proteoglycan metabolism and mineral crystals form in the dermis, possibly a response to abnormal collagen-proteoglycan interactions. These findings can be explained by a small defect in the product of one allele for pro-alpha 1(I) chains: three-quarters of the synthesized type I procollagen molecules are composed of trimers containing one or two chains defective near the C-terminus of the triple helix or in the C-propeptide. The data obtained for this patient confirmed that the severity of clinical manifestations in osteogenesis imperfecta strongly depends on the location and nature of the mutations, and that the phenotype could be a consequence of a collagen defect(s) and its influence on collagen-collagen interactions and collagen interactions with other connective tissue components.

Cells, Cultured↗
PubMed1987

Influence of short-term lithium carbonate administration on stimulated insulin secretion in normal man.

We have studied the effects of short-term treatment with lithium carbonate (900-1,200 mg/day for 4 days) on insulin secretion and blood glucose levels of 28 healthy volunteers (8 females and 20 males, aged 23-29 years) who underwent the following stimulations: two intravenous glucose loads of 25 and 5 g (IVGTT25; IVGTT5); arginine infusion (25 g over 30 min); tolbutamide test (0.25 g i.v.). Seven subjects for each group were tested. A placebo treatment was also performed. Short-term lithium treatment significantly reduced the insulin response to IVGTT25, arginine and tolbutamide. No differences were observed in blood glucose levels during all stimuli. Serum electrolyte levels and thyroid function were not affected by the treatment. In conclusion, these findings suggest, in healthy subjects, a good peripheral glucose utilization after brief-term lithium administration, in spite of impaired insulin response to various stimuli.

Adult↗
PubMed1987

Prolidase deficiency in two siblings with chronic leg ulcerations. Clinical, biochemical, and morphologic aspects.

Prolidase deficiency occurred in two sisters suffering from recurrent leg ulcers that appeared in early childhood. The patients presented the typical clinical symptoms of the disease, including characteristic facies, dermatologic manifestations of the lower extremities, splenomegaly, and hematologic anomalies. Large amounts of iminodipeptides were excreted into the urine, and prolidase activity in their erythrocytes was virtually absent. Changes associated with a connective-tissue disorder were demonstrated by light and electron microscopic studies of the patients' apparently normal skin. Collagen fibers were smaller than in controls and were irregularly packed; the fibrils had normal aspect but were significantly smaller than in one age-matched control. Elastin fibers appeared altered both in size and structure.

Adult↗
PubMed1983

Biochemical investigations of different forms of osteogenesis imperfecta. Evaluation of 44 cases.

Forty-four patients with Osteogenesis Imperfecta (O.I.) were divided into groups on the basis of clinical and genetic criteria and the alterations in collagen and glycosaminoglycans (GAG) in the subjects of each group were examined. The largest group of patients as affected with a mild form of O.I. and showed an increased ratio of type III to type I collagen in skin and an increase of the ratio of hydroxylysine diglycoside to monoglycoside in skin collagen. The group of patients affected with a severe nonlethal form of O.I. appeared to be heterogeneous both from a clinical and from a biochemical point of view. A marked increase of the diglycoside to monoglycoside ratio was observed in skin and urine, whereas the ratio of type III to type I collagen in skin was within the normal range or significantly decreased. Some of these patients also showed alterations involving proteoglycans, e.g. in urinary GAGs a decreased galactosamine to glucosamine ratio could be demonstrated. Similar and more marked alterations involving both collagen and GAG metabolism were observed in five children affected with a lethal form of O.I.

Collagen↗
PubMed1982

Biochemical and morphological modifications in rabbit Achilles tendon during maturation and ageing.

1. Achilles tendons of foetal, newborn, adult and old rabbits were examined by electron microscopy after staining by conventional methods or with the periodate/silver/methenamine technique. 2. The mean diameter of collagen fibrils increased with age whereas silver/methenamine-positivity became less evident. 3. Biochemical analyses showed a great decrease of the concentration of glycoproteins and galactosamine-containing glycosaminoglycans. 4. Collagen content increased with maturation and ageing of the tissue. 5. The extent of glycosylation of collagen hydroxylysine residues was also age-dependent; the total amount of hydroxylysyl glycosides rapidly decreased in the last days of prenatal life and in the first months after birth, corresponding to the rapid growth in collagen fibre diameter. 6. The hydroxylysyl diglycoside concentration decreased more markedly than that of the monoglycoside, thus indicating a possible gradual removal of the monosaccharide units. A role for the extent of glycosylation of tropocollagen molecules in fibre organization was suggested.

Achilles Tendon↗
PubMed1981

Fibrogenesis imperfecta ossium (clinical, biochemical and ultrastructural investigations).

The authors report a case of fibrogenesis imperfecta ossium (FIO). Only four cases diagnosed during life have previously been described in the literature. This is an extremely rare disease of entirely unknown aetiology. Clinical, biochemical and ultrastructural investigations were carried out. The most significant finding was the abnormal structure of the bone tissue, which was studied both by optical and electron microscopy on three successive biopsies of the iliac crest. In addition to deficient synthesis of the collagen fibrils, important anomalies related to the proteoglycans and the cellular elements were demonstrated. These have not been reported in previous cases. Some significant analogies with experimental lathyrism are also discussed.

Adult↗
PubMed1979

Biochemical and structural abnormalities of the connective tissue in Larsen's syndrome.

Skin, iliac crest cartilage and tendon of a patient affected with Larsen's syndrome were subjected to biochemical and ultrastructural investigation. A substantial increase in the ratio of glucosamine to galactosamine was found both in skin and cartilage. Ultrastructural abnormalities of collagen fibres and proteoglycan filaments were also found in Larsen's tissues. The significance of these findings are discussed.

Cartilage↗
PubMed1977

Osteogenesis imperfecta: morphological, histochemical and biochemical aspects. Modifications induced by (+)-catechin.

Two patients affected with two different forms of Osteogenesis Imperfecta were examined in order to study collagen and glycosaminoglycans (GAGs) in skin and iliac crest cartilage. A sharp decrease of the galactosamine to glucosamine ratio due to a reduced content of chondroitin sulfate was evidenced in both patients. Moreover the structure of proteoglycans appeared altered, this being more evident in the severe form of the disease. Morphological examination in light and electron microscopy of cartilage of the less severely diseased patient showed that GAGs in the extracellular matrix did not present regular connection with collagen fibers. Chondrocytes, elongated and disorderly scattered, showed large lipidic inclusions and, on histochemical basis, were devoid of UDPG dehydrogenase activity. Treatment with (+)-catechin produced an improvement, in both patients, of the biochemical pattern of collagen and GAGs. Similarly a shift of the cellular activity and of the matrix morphology towards normality was observed in the investigated cartilage of the less severely affected patient.

Adolescent↗