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Biomedical subjects

S Franc

Publications and source records attributed to S Franc.

At least 19 recordsLinked to original sources
PubMed2004

Prostatic neuroendocrine tumor in multiple endocrine neoplasia Type 2B.

We report the unusual occurrence of a neuroendocrine prostatic tumor in two young males with multiple endocrine neoplasia (MEN) 2B. Immunohistochemistry of the tumor markers may help differentiate a primary neuroendocrine prostate tumor from the metastasis of a medullary thyroid carcinoma of poor prognosis. MEN 2B hallmarks (i.e. plasma thyrocalcitonin and urinary metanephrines) may be systematically investigated in neuroendocrine tumors of the prostate, and conversely prostate examination may be performed in the periodic screening of MEN 2B male patients.

Adult↗
PubMed2001

Synthesis and structural organization of zonular fibers during development and aging.

Zonular fibers are a specific form of extracellular matrix composed mainly of fibrillins. The purpose of this study was to determine which cells secrete fibrillin-1 during development and aging. A specific guinea pig fibrillin-1 mRNA probe was designed and cloned in order to identify fibrillin-secreting cells in guinea pig eye, using in situ hybridization. Immunofluorescence, with a specific guinea pig monoclonal antibody, was used to compare protein levels at different stages from birth to 35 months of age. Electron microscopy and immunolabeling were used to investigate the organization of zonular microfibril bundles. We identified the cells of non-pigmented epithelium of the ciliary body as the main source of fibrillin secreted into the zonule. Moreover, while mRNA expression decreased during aging, there was no decrease in fibrillin immunoreactivity, as previously described in human aorta. These data indicate a very slow turnover of the zonular microfibrils which can be correlated with the appearance during aging of a new periodic fibrillar structure. This new structure may reflect an increased cross-linking in the long-lived zonular microfibrillar bundles.

Aging↗
PubMed2001

Complete surgical lymph node resection does not prevent authentic recurrences of medullary thyroid carcinoma.

BACKGROUND: Medullary thyroid carcinoma is a rare tumour derived from the thyroid parafollicular calcitonin-secreting cells. Calcitonin is a very specific marker of this cancer that allows preoperative diagnosis. Serum calcitonin assay is particularly useful to define the postoperative state of patients (cured, apparently cured, not cured) and, because of its great sensitivity, it has a major place in the postoperative follow-up. OBJECTIVE: To identify, among patients thyroidectomized for medullary thyroid carcinoma (MTC), the characteristics of authentic recurrent MTC [re-elevation of stimulated serum calcitonin (CT) level measured by a sensitive immunoradiometric assay, after postoperative normalization]. PATIENTS AND METHODS: We first collected, through the national registry of the French Calcitonin Tumour Study Group (GETC), patients who had undergone a total thyroidectomy with or without lymph node surgery and who were not cured at the last follow-up visit. Among 453 such patients included in the database, 15 patients met the criteria for authentic recurrence as defined in previous studies: they had been first considered as cured during the 6 months following the initial surgical procedure (basal and pentagastrin-stimulated serum calcitonin level <or= 10 ng/l) but had a secondary rerise of their pentagastrin-stimulated calcitonin level, over 10 ng/l. Eight of them even had an undetectable (< 2 ng/l) immediate postoperative CT, confirming the initial postoperative cure. The characteristics (age, nature of disease, stage at surgery and type of node dissection) of these 15 patients were studied. RESULTS: According to the Tumour Node Metastasis classification, nine patients were T1 and, among them, five patients had had complete lymph node surgery without any evidence of nodal metastases (N0). The recurrence was 3.2 +/- 2.2 years (range: 0.7-7.5) after the initial surgery. CONCLUSIONS: 3.3% of patients not cured at the last visit had a recurrent MTC. This recurrence occurred whatever the stage, and even if the primary surgery for MTC was a priori complete. These results emphasize the need for a regular biochemical follow-up because recurrence may appear many years after the initial surgery.

Adolescent↗
PubMed2001

Familial medullary thyroid carcinoma with noncysteine ret mutations: phenotype-genotype relationship in a large series of patients.

Familial medullary thyroid carcinoma only is related to germline mutations in the protooncogene RET, mainly in exons 10, whereas noncysteine mutations (exons 13-15) are considered infrequent. We analyzed 148 patients from 47 familial medullary thyroid carcinoma only families, and we found noncysteine RET mutations in 59.5% of these families. Of the index cases with noncysteine mutations, 43.4% presented with a multinodular goiter and high basal calcitonin; they were older at diagnosis than those with mutation in exon 10 and had more multifocal medullary thyroid carcinoma, but no difference in size, bilaterality, presence of C cell hyperplasia, or nodal metastases was found. Gene carriers with noncysteine RET mutations had a lower incidence of medullary thyroid carcinoma (78.2% vs. 94.1%) than those with mutation in exon 10; 20.2% had C cell hyperplasia only, although thyroidectomized at an older age. In conclusion, familial medullary thyroid carcinoma with noncysteine RET mutations are not infrequent and are overrepresented in presumed sporadic medullary thyroid carcinoma, suggesting that RET analysis should routinely be extended to exons 13, 14, and 15. The phenotype is characterized by a late onset of the disease, suggesting a delayed appearance of C cell disease rather than a less aggressive form. In familial medullary thyroid carcinoma gene carriers, the optimal timing for thyroidectomy remains controversial. Based on these data, we propose that surgery should be performed before elevation of the basal calcitonin level, potentially as soon as the pentagastrin test becomes abnormal.

Adult↗
PubMed2000

Lack of a phenotype in transgenic mice aberrantly expressing COL2A1 mRNA because of highly selective post-transcriptional down-regulation.

We reported previously that a 1.9-kb 5'-fragment from the human COL1A1 gene drove transcription of a promoterless human COL2A1 gene in tissues of transgenic mice that normally express the COL1A1 but not the COL2A1 gene. In the present study, we have established that the aberrant transcription of the COL2A1 gene did not produce any gross or microscopic phenotype, because the transcripts were not efficiently translated in cells that do not normally express the COL2A1 gene. In two lines of transgenic mice, the mRNA levels from the transgene were 30% to 45% of the mRNA for the proalpha1(I) chain of type I procollagen, the most abundant mRNA in the same tissues. Analysis of collagens extracted from skin of the transgenic mice indicated that triple-helical type II collagen, with the normal pattern of cyanogen bromide peptides, was synthesized from the transgene. However, the level of type II collagen in skin was less than 2% of the level of type I collagen. Hybridization in situ indicated the presence of mRNA for both COL2A1 and COL1A1 in the same cells. Immunofluorescence staining for type II collagen, however, was negative in the same tissues. The results, therefore, indicated that many mesenchymal cells in the transgenic mice had high steady-state levels of the homologous mRNAs for type I and type II procollagen, but only the mRNAs for type I procollagen were efficiently translated.

Animals↗
PubMed2000

[Assessment of the management of arterial hypertension in a population of (type 2) diabetic patients undergoing hospitalization. Diabetes and prognostic factors in the control of arterial hypertension].

The control of hypertension in diabetic hypertensive patients prevents micro and macroangiopathy complications. Our prospective study was designed to evaluate the level of treatment of hypertension in type II diabetic patients at the time of referral to our endocrinology unit and after a mean follow-up of 9.2 months. Five hundred and sixty four patients (sex ratio: 1.15, mean age of 56 +/- 13, mean BMI of 28 +/- 15, mean duration of diabetes of 11.3 +/- 9.9) were referred to our unit. Among these, 42% had an antihypertensive drug (58% under monotherapy, 42% under combinations) and 92% had a documented history of CHD. Glycemic and blood pressure controls were stable during follow-up. HbA1c remained unchanged (8.95% at admission, 8.8% at 9 months) BP decreased from 143/84 +/- 26/13 mmHg to 142/82 +/- 23/13 mmHg. Fifty six percent reached a BP goal of 140/90 mmHg whereas 42% achieved a BP goal of 130/85 mmHg at 9 months compared to respectively 56% and 39% at admission. A multivariate logistic regression analysis showed that initial value of SBP (p < 0.0001), age (p < 0.0001), BMI (p = 0.006), HbA1c (p = 0.018) were independent factors of non control of hypertension. In conclusion, follow-up of hypertension diabetic patients would be focussed on identified and modifiable factors.

Age Factors↗
PubMed1998

Microfibrillar composition of umbilical cord matrix: characterization of fibrillin, collagen VI and intact collagen V.

Ultrastructural studies made on human umbilical cord revealed that the striated collagen fibrils of the Wharton's jelly matrix are mixed with many microfibrillar structures. Microfibrils were found with a tubular cross-section of 10-12 nm diameter and were organized as beaded filaments characteristic of fibrillin-rich microfibrils. Beads had an average diameter of 25 nm and were spaced at about 50-80 nm. This ultrastructural observation was confirmed by indirect immunofluorescent staining of the jelly matrix using monoclonal antibody to fibrillin. Another constituent of the microfibrillar network was present as typical 100-nm periodic filaments of type VI collagen. Indirect immunofluorescent staining using antibodies to collagen VI showed for the first time that this collagen appeared to be distributed largely in the jelly matrix. In addition, other microfibrils with no specific banding pattern were observed. These microfibrils may constitute an organization of type V collagen different from the one which is generally assembled in heterotypic fibrils with collagen I. Among the latter heterotypic fibrils, type V collagen was studied using an anti-peptide antibody to the most N-terminal non-collagenous region of its alpha 2(V) chain. This antibody recognized a filamentous mesh decorating the bundles of collagen fibrils by immunofluorescent staining. This indicates that at least this part of alpha 2(V) chain may be accessible to the antibody at the surface of the fibrils.

Actin Cytoskeleton↗
PubMed1998

Atomic force microscopy and modeling of natural elastic fibrillin polymers.

A central issue in the understanding of Marfan syndrome deals with the functional architecture of fibrillin-containing microfibrils. Fibrillin-rich microfibrils are long extracellular matrix fibrillar components exhibiting a 50 nm periodic beaded-structure with a width of around 20-25 nm after rotary shadowing and a 10-12 nm diameter when observed in ultra-thin sections. They are composed of fibrillin monomers more or less associated with many other components which are, for the most part, poorly characterized up to date. They are known to be elastic but few data have been accumulated to understand their properties. Atomic force microscopy (AFM) allowed us to morphologically differentiate fibrillin-rich microfibrils from other fibrillar components and to investigate the thin structure of these beaded filaments in their native state. They showed, in AFM, a periodic beaded structure ranging from 50 to 60 nm and a width of about 40 nm. The different sizes of fibrillin-containing microfibrils previously observed after rotary shadowing and in ultra-thin sections was resolved with our technique and is revealed to be 10 nm in diameter. Each beaded microfibril appears to be composed of heterogeneous beads connected by 2-3 arms. An orientation of the microfibrils has been shown, and allows us to propose a complementary model of microfibrillar monomer association.

Animals↗
PubMed1998

Fibrillin-rich microfibrils: structural modifications during ageing in normal human zonule.

Ageing is marked by ultrastructural and functional changes in most tissues. In part, these changes are caused by a loss of elasticity in the elastic fibers of the extracellular matrix. These fibers are composed of the protein elastin associated with microfibrils of 8 to 12 nm in diameter. Microfibrils contain fibrillins as major constituents. Mutations in fibrillin genes are considered as primary causes of Marfan syndrome, a genetic disorder with pathological manifestations in the cardiovascular and skeletal systems, in addition to dysfunctions in the eye. Fibrillin is also the major protein of the ciliary zonule fibers. During ageing, these fibers become more fragile, and concomitantly, an increased risk for ocular pathologies is observed. We have investigated structural modifications in fibrillin-rich microfibrils during ageing of human ciliary zonule. Observations using light microscopy and transmission electron microscopy after rotary shadowing allowed us to describe the organization of the zonule fibers and their insertion into the ciliary body. Our results emphasize qualitative differences between young and old zonules, which are likely due to modifications in the structure of microfibrils.

Actin Cytoskeleton↗
PubMed1997

[Rhabdomyolysis in patients with preexisting myopathy, treated with antilipemic agents].

BACKGROUND: Lipid lowering drugs (fibrates and statins) are generally well tolerated and side effects, mainly hepatic and muscular disorders are rare. However, when they occur, muscular disorders may be severe, leading to rhabdomyolysis. We report here four cases of rhabdomyolysis in patients given lipid lowering drugs and who had pre-existing myopathy. CASE REPORTS: The four patients complained of muscle pain after treatment with niacin, HMGCoA inhibitors, as well as fibrates. The myopathy was not recognized at the time of prescription in three cases. Myopathy resolved rapidly upon discontinuation of the drugs and none of the patients developed renal failure. DISCUSSION: This is the first report of rhabdyomyosis induced by lipid lowering drugs in patients with pre-existing myopathy. Drug induced myopathy is a known complication of lipid lowering drugs either alone or in patients with other conditions such as renal failure, immunosuppressive therapy for cardiac transplantation, or in case of combination regimens. Such a side effect without concomitant disease has not been reported previously in patients with congenital myopathy. Cholestyramine is the drug of choice for these patients. Our observations suggest that the rhabdomyolysis provoked by lipid lowering drugs may be favored by pre-existing myopathy.

Adult↗
PubMed1997

Vasculitis confined to the calves. Report of a case.

Polyarteritis nodosa is a systemic disease of which limited forms have been reported, with the most common involving the skin. Only 13 cases with lesions confined to the calves have been reported to date. We report a new case.

Female↗
PubMed1996

The evolution of fibrillar collagens: a sea-pen collagen shares common features with vertebrate type V collagen.

The extracellular matrix of marine primitive invertebrates (sponges, polyps and jellyfishes) contains collagen fibrils with narrow diameters. From various data, it has been hypothesized that these primitive collagens could represent ancestral forms of the vertebrate minor collagens, i.e., types V or XI. Recently we have isolated a primitive collagen from the soft tissues of the sea-pen Veretillum cynomorium. This report examines whether the sea-pen collagen shares some features with vertebrate type V collagen. Rotary shadowed images of acid-soluble collagen molecules extracted from beta-APN treated animals, positive staining of segment-long-spacing crystallites precipitated from pepsinized collagen, Western blots of the pepsinized alpha1 and alpha2 chains with antibodies to vertebrate types I, III and V collagens, and in situ gold immunolabeling of ECM collagen fibrils were examined. Our results showed that the tissue form of the sea-pen collagen is a 340-nm threadlike molecule, which is close to the vertebrate type V collagen with its voluminous terminal globular domain, the distribution of most of its polar amino-acid residues, and its antigenic properties.

Amino Acid Sequence↗
PubMed1995

Immunohistochemical and biochemical analyses of 20,000-25,000-year-old fossil cartilage.

A cracked, irregular pellicle adhering to fossilized bone excavated from the Enlène cave (Ariège) and estimated to date from 20,000-25,000 years BP was examined to verify its cartilaginous nature, suggested previously on the basis of optical and electron microscopic investigations. Immunolabeling of the organic component revealed the presence of type II and IX collagens, associated with residual glycosaminoglycans, in the external zone of the pellicle. The cartilaginous nature of the pellicle was also demonstrated by biochemical identification of type II collagen as the major protein in the demineralized sample: the amino acid compositions of insoluble and soluble fractions were similar to that of pure type II collagen; cyanogen-bromide-generated peptides, prepared after reduction of the sample, had an electrophoretic pattern similar to that of cyanogen bromide peptides derived from type II collagen. The amino acid sequences of four tryptic peptides were identical to the corresponding human type II sequences. It was impossible to isolate intact alpha chains. All of the solubilized fractions were composed of a wide range of low-molecular-mass peptides demonstrating significant degradation of the collagen molecules that was not reflected in the well-preserved fibrillar structure observed at the ultrastructural level. The mineral fraction, characterized by X-ray diffraction, consisted of apatite (as in sub-chondral bone) associated with contaminating poorly crystallized components originating from the cave sediment. Energy dispersive spectrometry showed that the cartilaginous zone contained three times less phosphorus and calcium than the underlying bone. These results confirm the cartilaginous nature of the sample and the preservation of tissue-specific components, and suggest that the process of fossilization is closely related to a mechanism of phosphatization.

Amino Acid Sequence↗
PubMed1994

Mutation in the COL2A1 gene in a patient with hypochondrogenesis. Expression of mutated COL2A1 gene is accompanied by expression of genes for type I procollagen in chondrocytes.

A new dominant mutation in the COL2A1 gene was found in a 38-week-old fetus with hypochondrogenesis. Denaturing gradient gel electrophoresis was used to analyze all 44 exons coding for the triple-helical domain of COL2A1 gene and the corresponding exon-intron boundaries. The technique detected a new sequence variation in exon 35. Sequencing of exon 35 demonstrated a single base mutation that converted the codon for glycine at position 604 to a codon for alanine. Electrophoresis of pepsin-digested collagen extracted from the diseased cartilage showed a doublet band of the alpha 1(II) chain of type II collagen and the presence of alpha 1(I) and alpha 2(I) chains of type I collagen. Two-dimensional analysis of cyanogen bromide peptides from the type II collagen revealed post-translational overmodification of peptides CB12, CB11, CB8, and CB10.5, whereas peptide CB9.7 migrated normally. Microscopic examination of cartilage showed that the mutation altered the organization of the growth plate. Also, articular chondrocytes contained large cisternae of rough endoplasmic reticulum. The density of the extracellular matrix was reduced, and the intensity of the staining with an antibody to type II collagen was diminished. In contrast, a significant staining with an antibody to type I collagen was observed. In situ hybridization with cRNA probes revealed a significant level of alpha 1(I) mRNA in the cytoplasm of the patient's chondrocytes. The signal for alpha 1(II) mRNA was about the same in control samples. The results indicated, therefore, that the genes for both type I and type II procollagens were simultaneously expressed in chondrocytes from the patient.

Adult↗
PubMed1993

[Phylogenesis of the extracellular matrix].

The extracellular matrix constitutes a highly organized intercellular medium. In multicellular animals, it plays important functions for cell cohesion and for the modulation of cell differentiation and behaviour as well. All the investigations conducted in non-vertebrate species have shown that the extracellular matrix is present at the onset of the multicellular life and throughout the animal kingdom. The collagen fibrils are the most constant element. Recent data on the structure of fibrillar collagen molecules and on the organization of the corresponding genes, obtained in sponges and sea-urchins have shown the remarkable conservation of these fibrillar collagens during evolution. This even emphasize their very likely fundamental function. These results, associated with data provided by morphological and biochemical informations obtained in cnidarians suggest that these primitive fibrillar collagens are the direct precursors of some vertebrate minor fibrillar collagens such as type V. Other collagens, with interrupted triple helix, are more variable and their characterization in sponges leads to consider these non-fibrillar collagens as precursors of basement membrane collagens, of fibril-associated collagens (the FACITs collagens), of the so-called "epithelial" collagens. They were probably used as sticking devices, anchoring the animal to its substratum, or as covering layers (cuticles, sheaths), and even as skeletons (i.e. the bath sponge). Adhesive molecules of higher animals ensure the mediation of the interactions between cells (via their membrane receptors of the integrin type) and the fibrous network of the extracellular matrix. It is the same situation at the beginning of the evolution of the multicellular animals where fibronectin, tenascin and then laminin are present. Proteoglycans too are components of primitive extracellular matrices. At last, only collagen mineralized by calcium phosphate (in bone) and elastin (in elastic fibers and laminae) seem to be restricted to vertebrates.

Animals↗
PubMed1993

Ultrastructural evidences of a distinct axial domain within native rat tail tendon collagen fibrils.

The structure of collagen fibrils of tail tendon in young and mature rats was investigated by transmission (TEM) electron microscopy after cytochemical methods associated with special procedures of dehydration and fixation. All the collagen fibrils show a central condensed material of 4 nm in diameter which remains preserved even when fibrils have been swollen and partly disorganized by the ethyl glycol dehydration. A cytochemical characterization using PTA and TCH treatments strongly suggests the glycoprotein nature of this central compact material and reveals the heterogeneous structure of each fibril. The first morphological evidence that the construction of the collagen fibrils must take place around a condensed material which serves as a scaffolding is obtained. These observations are in agreement with the now well established existence of heterotypic collagen fibrils in many extracellular matrices.

Age Factors↗
PubMed1992

Characterization of heterotrimeric collagen molecules in a sea-pen (Cnidaria, Octocorallia).

The collagen of a primitive invertebrate, the sea-pen Veretillum Cnidaria, Octocorallia), was studied with respect to its molecular-chain composition. The soft extracellular tissues (mesoglea) were solubilized by limited pepsin proteolysis and the collagen was isolated by selective precipitation at 0.7 M NaCl under acidic conditions. The pepsinized molecules were 260 nm in length, as demonstrated by electron microscope studies of rotary-shadowed molecules and of the segment-long-spacing crystallites obtained by dialysis against ATP. SDS/PAGE of the extract produced two main bands susceptible to bacterial collagenase, designated as the alpha 1 and alpha 2 chain, which were differentiated clearly by their CNBr cleavage products and the higher glycosylation rate of the alpha 2 chain. The latter finding corresponds with the high hydroxylysine content of the alpha 2 chain. The alpha 1/alpha 2 chain ratio observed in SDS/PAGE and the fact that only one peak was obtained by concanavalin-A affinity chromatography of a non-denatured 0.7 M NaCl extract demonstrate the alpha 1 [alpha 2]2 molecular structure of this collagen. These results contrast with data on the structure of other coelenterates (i.e. [alpha]3 for sea anemone collagen molecules and alpha 1 alpha 2 alpha 3 for jellyfish collagen molecules). They are discussed in relation to the evolution of collagen.

Amino Acids↗