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Biomedical subjects

E Marbaix

Publications and source records attributed to E Marbaix.

At least 37 records · Page 2Linked to original sources

Expression of interstitial collagenase (matrix metalloproteinase-1) is related to the activity of human endometriotic lesions.

OBJECTIVE: To determine whether interstitial collagenase (matrix metalloproteinase-1), known to play a pivotal role in the initiation of menstruation, contributes to the pathogenesis of endometriosis. DESIGN: Serial sections of peritoneal red and black endometriotic lesions, ovarian endometriotic cysts, and rectovaginal adenomyotic nodules were analyzed by in situ hybridization for the expression of matrix metalloproteinase-1 by silver staining for the integrity of the fibrillar extracellular matrix and by immunolabeling for the abundance of sex steroid receptors. SETTING: Academic hospital and research laboratory. PATIENT(S): Premenopausal women undergoing laparoscopy for endometriosis. INTERVENTION(S): Biopsy of endometriotic lesions, combined with endometrium whenever possible. MAIN OUTCOME MEASURE(S): Expression of matrix metalloproteinase-1 messenger RNA (mRNA). RESULT(S): Matrix metalloproteinase-1 mRNA was expressed focally in red peritoneal and ovarian endometriosis irrespective of the phase of the menstrual cycle but was not detectable in black peritoneal and rectovaginal lesions. Foci of matrix metalloproteinase-1 expression closely correlated with matrix breakdown and with the absence of P receptors in adjacent epithelial cells. CONCLUSION(S): Correlation of matrix metalloproteinase-1 expression with activity of endometriotic tissue suggests its involvement in tissue remodeling and bleeding, and possibly in the secondary shedding and reimplantation of endometriotic lesions.

Adult↗

Menstrual breakdown of human endometrium can be mimicked in vitro and is selectively and reversibly blocked by inhibitors of matrix metalloproteinases.

The mechanisms underlying the menstrual lysis leading to shedding of the human endometrium and its accompanying bleeding are still largely unknown. In particular, whether breakdown of the endometrial fibrillar extra-cellular matrix that precedes bleeding depends on aspartic-, cysteine-, serine-, or metalloproteinases remains unclear. In the present study, menstrual regression of the human endometrium was mimicked in organ culture. Whereas sex steroids could preserve tissue integrity only in nonperimenstrual explants, matrix breakdown upon sex steroid deprivation was completely and reversibly inhibited at all stages of the menstrual cycle by specific inhibitors of matrix metalloproteinases, but not by inhibitors of the other classes of proteinases. Matrix metalloproteinases are thus identified as the key class of proteinases involved in the initiation of menstruation.

Collagen↗

Morphometric, immunohistological and three-dimensional evaluation of the endometrium of menopausal women treated by oestrogen and Crinone, a new slow-release vaginal progesterone.

Recently advanced computerized technology was applied to the investigation of morphometric, immunohistological and three-dimensional changes of the endometrial mucosa in order to evaluate quantitatively the effects of three doses of a new slow-release vaginal progesterone on the endometrium in post-menopausal women. A total of 20 menopausal women, deprived of ovarian function, were given oestrogen for 12 days and a combined therapy of oestrogen (administered orally) and progesterone for another 12 day period. Progesterone was administered vaginally through a new gel (Crinone) utilizing a bioadhesive, biocompatible polymer as a base to achieve a sustained release effect. An endometrial biopsy was taken before treatment, after oestrogen-only treatment and after the oestro-progestogen therapy. Before treatment, all the patients exhibited an atrophic endometrium. After oestrogen-only treatment, typical proliferative changes occurred: an increase in the endometrium thickness, an increase in the mitotic index, numerous cylinder-like glands and no coiled glands, and high concentrations of oestrogen receptors (ER) and progesterone receptors (PR). After the oestro-progestogen therapy, whatever the dose of progesterone given, a secretory transformation of the endometrial mucosa occurred, mitotic activity decreased significantly, more ramified and coiled glands were observed, and a decrease in PR content was noted in epithelial and stromal nuclei, and a decrease in PR content was also observed in epithelial nuclei but not in stromal nuclei. Accurate new techniques of image analysis have shown that crinone therapy could eliminate the proliferative effects of oestrogen treatment in post-menopausal women, despite doses as low as 45 mg of progesterone administered vaginally every other day. The results suggest that the sustained release effects of Crinone are clinically relevant.

Capillaries↗

Regulation and restricted expression of interstitial collagenase suggest a pivotal role in the initiation of menstruation.

Collagenases are the only mammalian enzymes able to cleave, at neutral pH, the triple helical domain of fibrillar collagens, major constituents of the extracellular matrix of the endometrium. Interstitial collagenase is expressed, secreted and activated in human endometrium only just before and during menstruation. The expression of interstitial collagenase is restricted to the areas of the functional layer of the endometrium which are breaking down and to fragments which have been shed. In endometrial explants, combined sex steroids tightly control the expression, secretion and activation of interstitial collagenase, as well as the preservation of the extracellular matrix. These observations imply a pivotal role for this proteinase in the initiation of menstruation.

Biopsy↗

Focal cellular origin and regulation of interstitial collagenase (matrix metalloproteinase-1) are related to menstrual breakdown in the human endometrium.

Recent studies suggest that interstitial collagenase (MMP-1) is an essential enzyme in the early events leading to menstruation. This study analyses its cellular origin, regulation and relation to extracellular matrix breakdown in the human endometrium, both in cultured and non-cultured samples. The source of MMP-1 was identified by in situ hybridization and by immunohistochemistry on serial sections. This was compared with the immunolocalization of other MMPs, steroid receptors, macrophages, and laminin. In non-cultured endometrium, MMP-1 was only expressed during the perimenstrual period. It was either restricted to superficial foci of stromal cells or extended towards the entire functional layer. MMP-1 expression remarkably correlated with matrix breakdown, as assessed by silver staining, and was prominent at the periphery of shedding fragments and along some arterioles. In cultured non-menstrual explants, MMP-1 expression was induced within two days after deprivation of sex steroids. Both in cultured and non-cultured samples, progesterone receptors were not detectable in epithelial cells at foci of MMP-1 expression. The same stromal cells could synthesize MMP-1, MMP-2 (gelatinase A) and MMP-3 (stromelysin-1), as well as laminin, and did not correspond to macrophages. In conclusion, MMP-1 is focally expressed in stromal cells of the functional layer of the endometrium, when and where steroid receptors disappear, and especially where tissue breakdown is prominent. These observations point to an essential role for MMP-1 in the early stages of menstruation.

Collagenases↗

The expression of interstitial collagenase in human endometrium is controlled by progesterone and by oestradiol and is related to menstruation.

Human endometrial tissue, sampled at different periods of the reproductive cycle, expressed interstitial collagenase mRNA, protein and activity only just before and during the menstrual period. This clear-cut correlation and the inhibition of collagenase expression by progesterone and oestradiol in tissue culture point to a pivotal role of this proteinase in the mechanism of menstrual tissue breakdown and bleeding.

Blotting, Northern↗

[Granulocytic sarcoma of the larynx. Report of a case and literature review].

Granulocytic sarcoma of the larynx. Case report and review of the literature. Granulocytic sarcoma is a rare extramedullary tumor. It occurs either as an isolated tumor or associated with acute or chronic myelogenous leukemia. It has also been reported in patients with myelodysplastic syndromes when the granulocytic sarcoma is a harbinger of imminent disease progression. Granulocytic sarcoma can occur anywhere in the body. The larynx is a rare site of this lesion. A first case of glottic localisation is presented. The treatment of granulocytic sarcoma must include surgery, radiation and chemotherapy.

Aged↗

[Effect of local medications on intraocular pressure control following trabeculectomy].

Longterm administration of topical antiglaucoma therapies had been indicated to be a serious risk for failure of trabeculectomy through inducing a subclinical inflammation of conjunctival tissues and stimulating secondary fibroblastic proliferation. Our study had 3 main aims: (1) to check if this pejorative effect is present in our population of glaucomatous patients, (2) in order to improve the rate of surgical success in theoretically high risk patients (duration of topical treatment longer than 36 months), to determine the usefulness of the following actions: suppression of beta blocking agents 8 days before surgery, suppression of miotics and eventual topical administration of fluorometholone one month before surgery. (3) to correlate the observed clinical results to the cellular profile of preoperative conjunctival biopsies. We presented in a first step the results of a retrospective analysis including 88 trabeculectomies performed between January '93 and April '95 in 62 GCAO patients older than 40 years and without any previous ocular surgery. The mean age of patients was 66,8 years (41 to 87 years). Patients were classified into "complete success", "qualified success" and "failures" according to the "target" IOP was or was not reached in the last examination. Mean follow up was 5,8 months (1 to 26 months). The second prospective part of our study included 20 trabeculectomies performed in 16 patients we chose according to the nature, the duration of the preoperative topical therapy and the preoperative eventual preparation of the conjunctiva. This study also included a semiquantitative count of the different conjunctival cellular colonies in peroperative biopsies. Mean follow up of this study was 2,3 months (1 to 5 months). 31 "complete success", 52 "qualified success" and 5 "failure" were observed in the retrospective study. The reduction of IOP following trabeculectomy was statistically significant at all examinations (mean IOP in the last examination: 14,9 +/- 4,3 mmHg) but the level of success was not significantly different according to the nature, (mono against polytherapy), the duration of preoperative medical topical treatment, as well as the preoperative actions in order to improve the operative success in high risk patients. Preliminary results of our second prospective study did not yet show any failure and did not exhibit any clear correlation between the counts of the different cellular colonies and the level of operative success on one hand and the different topical therapies in the other hand. The results and limitations of this study were compared to those of the literature.

Adrenergic beta-Antagonists↗

[Central odontogenic fibroma].

Odontogenic fibroma is an infrequent benign tumor, originating in the mesenchyma and including an inactive odontogenic epithelial component. The central form, of which one case is reported here, is expressed by a relatively well-delineated radiolucent area, whose interest and difficulty lie in the differential diagnosis. On the basis of a review of the literature, details are given on the clinical, clinicopathologic, diagnostic and therapeutic data.

Adolescent↗

Progesterone regulates the activity of collagenase and related gelatinases A and B in human endometrial explants.

Explants of human endometrium were cultured to study the release of matrix metalloproteinases (MMPs). Analysis of conditioned media by zymography revealed latent and active forms of collagenase (MMP-1, EC 3.4.24.7), 72-kDa gelatinase A (MMP-2, EC 3.4.24.24), and 92-kDa gelatinase B (MMP-9, EC 3.4.24.35). These proteinases were identified by their M(r), their inhibition by tissue inhibitor of metalloproteinases, and the activation of their zymogens by trypsin or aminophenylmercuric acetate. In the absence of sex hormone, explants released large amounts of enzyme activities, as measured by densitometry of zymograms or in soluble assays. Physiological concentrations of progesterone (10-200 nM) almost totally abolished the release of collagenase, of total gelatinase activity, and of the active form of gelatinase B and largely inhibited the release of the active form of gelatinase A. These effects, which were antagonized by mifepristone (RU 38486), suggest that progesterone restrains endometrial tissue breakdown by blocking the secretion and activation of MMPs.

Collagenases↗

[Exudative laryngeal diseases of Reinke's space].

Exudative laryngopathies are represented by the nodule, the polyp and the Reinke's oedema. Their origin is found in exudative processes located in the Reinke's space. Evolution towards one or another lesion depends on the etiological factor (vocal abuse, tobacco, alcohol, acute vocal fold trauma) and can happen according three modalities: oedema, fibrosis and angiectasies development. Apparition of fibrosis inside the lesion or too important haemorrhage require microsurgical treatment in addition to the medical treatment and the speech therapy.

Humans↗

A comparative analysis of healing of surgical cleft lip corrected in utero and neonates.

We studied the healing process in surgically created cleft lips in fetal mice and compared it with that in newborn mice with cleft lips. Our purpose was to determine the time for optimal healing, defined as minimal scarring, for a repaired cleft lip. Full-thickness paramedian lip incisions were made in NMRI mice in utero, in 2- and 4-day-old neonates, and in adults (n = 10 in each experimental and control group). The healing process was studied by biochemical analysis of hyaluronic acid and hydroxyproline content in the repaired cleft tissue. We found that the production of hyaluronic acid remained stable during the healing period and was similar in all experimental groups. However, there was an unexplained but consistent depression in the hyaluronic acid content of fetal tissue 2 days after repair. Hydroxyproline was present in the fetal healing tissue, but in a low concentration, starting 4 days after surgical incision of the lip. The production of hydroxyproline in 2-day-old neonates was similar to that in the fetuses throughout the healing period (p less than 0.0005). However, the production of hydroxyproline increased in 4-day-old neonatal and adult tissues. In conclusion, we found an optimal healing period for mice with minimal collagen production in the late fetal stage, and this lasted 2 days after birth.

Aging↗

Tissue integration of the collagen-hydroxylapatite implant: histological examination in canine bone and surrounding tissues.

Using the dog as an animal model, we have tested an implant material composed of purified fibrillar collagen (PFC) and particulate hydroxylapatite (HA) in the mandible and in surrounding tissues. Bone and tissue samples were taken at 2, 4 and 6 months for histological study. After 2 months, the PFC was replaced by fibro-connective host tissues. After 4 months, some small areas of ossification were observed around the HA particles. After 6 months, the fibro-connective tissue was replaced by neo-formed bone in the mandible. PFC was found to increase the interfaces between the HA particles and the host tissues, permitting HA integration into the bone. The PFC/HA implant was also molded when moistened by blood or saline solution and then became mis-sharpen by local pressures exerted. These findings show that the implant should preferably be reserved for the restoration of bones not subjected to significant forces or local stresses.

Animals↗

Lysosomal enzymes in the human endometrium: a biochemical study in untreated and levonorgestrel-treated women.

The activities of four lysosomal enzymes, i.e. N-acetyl-beta-hexosaminidase, acid phosphatase, alpha-D-mannosidase and alpha-L-fucosidase have been measured in extracts of endometrial biopsies from untreated and levonorgestrel-treated women of fertile age. Values were compared with protein and DNA content, as well as with lactate dehydrogenase activity, used as reference constituents. In parallel, organ cultures were established from the same endometrial specimens and the release of lysosomal enzymes into the medium was followed. The human endometrium possesses a rich lysosomal equipment, comparable to that found in the human liver. In the untreated cycles, the activities of lysosomal enzymes show a coordinate response to the hormonal changes, decreasing by about 40% from the proliferative to the mid-late secretory phase. Long-term levonorgestrel treatment causes a marked cytoplasmic atrophy, as shown by decreased protein content and lactate dehydrogenase activity, whereas DNA content remains unchanged. In contrast, N-acetyl-beta-hexosaminidase, one of the most active lysosomal enzymes studied, shows a higher specific activity upon levonorgestrel. In both untreated and treated endometria, the organ cultures provide biochemical evidence for a higher release of N-acetyl-beta-hexosaminidase than of lactate dehydrogenase, indicating active secretion of the lysosomal enzyme. During levonorgestrel treatment, there was no correlation between clinically recognized spotting-bleeding patterns and lysosomal enzyme content in, or release from, the endometrium.

Acetylglucosaminidase↗

Further morphologic studies on collagen injected into canine vocal folds.

We compared the morphologic fate of three types of soluble bovine collagen injected into vocal folds of dogs: 1) Zyderm collagen implant containing 35 mg/mL of collagen (ZCI I), 2) Zyderm collagen implant containing 65 mg/mL of collagen (ZCI II), and 3) GAX collagen containing 35 mg/mL of collagen minimally cross-linked with 0.0075% glutaraldehyde. Light and electron microscopy showed good host tolerance and a long-term persistence of the three types of collagen at the site of injection. The collagen implants were progressively colonized by fibroblasts and capillaries accompanied by host collagen deposition. No inflammatory process or foreign body reaction occurred, in contrast to the typical host reaction to injected Teflon. The colonization of GAX collagen was slower than for ZCI I and ZCI II. No other significant difference was evident among the three types of injectable collagen. All three appear to be very suitable materials for laryngeal implants; moreover, they seem to best meet accepted requirements for a good implant: they are easy to inject, they are well tolerated, and they persist for a long time. We prefer GAX collagen for clinical use because of its lower reactivity and higher stability, and because overinjection is not necessary (GAX shrinks less than ZCI I and ZCI II).

Animals↗

GAX-collagen in the human vocal fold.

A report is presented of the first histological study of GAX-collagen injected into the human vocal cord. The study concerns a specimen from an arytenoidectomy performed 28 months after injection. As it had already been the case in the animal, the excellent integration of GAX-collagen with the host-tissues has been noted, as well as the stability of the result more than 2 years later. It also appeared that colonization of GAX-collagen by the host cells is less rapid than for the ZCI. While inflammatory reaction is weak in the region of the GAX-collagen, there is to be seen some atrophy and fibrosis of the muscular fibres around the deposit, probably due to compression during injection.

Collagen↗