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Biomedical subjects

D Goldschmidt

Publications and source records attributed to D Goldschmidt.

At least 19 recordsLinked to original sources
PubMed1999

Amelioration of ischemia-reperfusion injury in rat intestine by pentoxifylline-mediated inhibition of xanthine oxidase.

BACKGROUND: Intestinal ischemia-reperfusion (IR) injury results in cell destruction, which may be mediated by the generation of reactive oxygen species, potentially toxic metabolites of xanthine oxidase. Pentoxifylline (PTX) possesses a variety of biochemical and antioxidant properties that can improve capillary flow and tissue oxygenation. Because of these combined effects, it has been hypothesized that pentoxifylline would protect against intestinal IR. METHODS: Young adult rats were randomly assigned to one of four experimental groups: IR/Placebo (n = 12) in which superior and inferior mesenteric arteries were clamped for 45 minutes and then reopened; IR/PTX (n = 11) in which IR was induced as in the Placebo group, but with 25 mg/kg PTX at 0, 30, and 60 minutes; No IR/Placebo (n = 12); and No IR/PTX (n = 6) in which placebo and PTX were applied with no IR. Blood and intestinal samples were taken for serial thiobarbituric acid-reducing substances (TBARS; index of lipid peroxidation), for xanthine oxidase-xanthine dehydrogenase ratios, glutathione, myeloperoxidase, and histopathology. RESULTS: Animals in the IR/PTX group had lower TBARS and the least severe histopathologic injury. Xanthine oxidasexanthine dehydrogenase ratios were elevated only in IR/ Placebo (0.67+/-0.22 vs. 0.45+/-0.14 in IR/PTX; 0.42+/-0.22 in No IR/Placebo; and 0.40+/-0.11 in No IR/PTX; p = 0.0009). Reduced glutathione was diminished in IR/PTX animals (38.9 +/-1.35 vs. 46.1+/-7.0 in IR/Placebo; 41.1+/-2.5 in No IR/ Placebo; 43.6+/-1.0 in No IR/PTX; p = 0.048). No differences were recorded in myeloperoxidase levels among groups. CONCLUSIONS: Pentoxifylline ameliorates histopathologic signs of injury and decreases lipid peroxidation (TBARS). Normal xanthine oxidase-xanthine dehydrogenase ratios in the treated compared with IR-only animals imply that the protective effect of PTX is at least partially mediated through inhibition of xanthine oxidase.

Animals↗
PubMed1998

Structural requirements for fibromodulin binding to collagen and the control of type I collagen fibrillogenesis--critical roles for disulphide bonding and the C-terminal region.

Fibromodulin belongs to the family of small, leucine-rich proteoglycans which have been reported to interact with collagens and to inhibit type I collagen fibrillogenesis. Decorin and fibromodulin exhibit a noticeable degree of sequence similarity. However, as previously reported [Font, B., Eichenberger, D., Rosenberg, L. M. & van der Rest, M. (1996) Matrix Biol. 15, 341-348] the domains of these molecules implicated in the interactions with type XII and type XIV collagens are different, these being the dermatan sulphate/chondroitin sulphate chain for decorin and the core protein for fibromodulin. At the present time the fibromodulin domains implicated in the interactions with fibrillar collagens remain unknown. In experiments reported here, we have sought to identify the structural requirements for fibromodulin interaction with collagen and for the control of type I collagen fibrillogenesis. Circular dichroism spectra and fibrillogenesis inhibition studies show that fibromodulin structure and its collagen fibrillogenesis control function are strictly dependent on the presence of intact disulphide bridge(s). In addition, we show that the binding of fibromodulin (or fibromodulin-derived fragments) to type I collagen is not necessarily correlated with fibrillogenesis inhibition. To isolate fibromodulin domains, the native proteoglycan was submitted to mild proteolysis. We have isolated an alpha-chymotrypsin-resistant fragment which contains the bulk of the N-terminal and central region of the molecule including the leucine-rich repeats 4 and 6 reported for decorin to be involved in type I collagen binding. This fragment does not bind to type I collagen. Using enzymes with different specificities, a number of large fragments of fibromodulin were obtained, suggesting a compact structure for this molecule which is relatively resistant to proteolysis. None of these N-glycosylated fragments were able to bind to type I collagen in co-sedimentation experiments. Taken together these results suggest that fibromodulin-type I collagen interactions leading to fibrillogenesis inhibition require more than one binding domain. One of these domains could be the C-terminal end of the molecule containing the disulphide loop which is absent in the chymotrypsin-resistant fragment.

Amino Acid Sequence↗
PubMed1998

The in vitro influence of eight hormones and growth factors on the proliferation of eight sarcoma cell lines.

Little is known about the regulation of sarcoma proliferation by hormones and/or growth factors. We therefore characterised the in vitro proliferative influence on eight sarcoma cell lines of the platelet-derived growth factor, the insulin-like growth factor 1, triiodothyronine, the epidermal growth factor, the luteinising-hormone-releasing hormone, progesterone, gastrin and 17 beta-oestradiol. The influence of the different factors on the proliferation of sarcoma cell lines was measured by the colorimetric 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide test. Two culture media were studied: (1) a nutritionally poor medium containing 2% of fetal calf serum and (2) a nutritionally rich one containing 5% or 10% FCS both with and without the addition of non-essential amino acids. The results were analysed either by conventional statistical analyses or by a classification method based on a decision-tree approach developed in Machine Learning. This latter method was also compared to other classifiers (such as logistic regression and k nearest neighbours) with respect to its accuracy of classification. Monovariate statistical analysis showed that each of the eight cell lines exhibited sensitivity to at least one factor, and each factor significantly modified the proliferation of five or six of the eight cell lines under study. Of these eight lines one of fibrosarcoma origin was the most "factor-sensitive". Decision-tree-related data analysis enabled the specific pattern of factor sensitivity to be characterised for the three histological types of cell line under study. The effects of hormone and growth factors are significantly influenced by the type of culture medium used. The method used appeared to be an accurate classifier for the kind of data analysed. Sarcoma proliferation can be modulated, at least in vitro, by various hormones and growth factors, and the proliferation of each histopathological type exhibited a distinct sensitivity to different hormone and/or growth-factors.

Cell Division↗
PubMed1998

Traumatic spinal accessory nerve palsy.

Spinal accessory nerve sections due to a purely traumatic origin are very rare. The authors report a case in which a total section of the spinal accessory nerve was observed after a glass-penetrating injury. The primary lesion was undiagnosed, and only late physical examination revealed a scapula alata with a deficiency in shoulder protrusion and elevation. Surgical exploration with direct suturing of the nerve was performed 2 months after the initial trauma; full restoration of muscle function was obtained 12 months after the surgical procedure. Pain, the dominant preoperative feature, totally disappeared after restoration of shoulder function. Although infrequent, spinal accessory nerve lesions must always be excluded in cases of penetrating injuries in the posterior triangle of the neck. Emphasis is placed on diagnosis and treatment of this condition.

Accessory Nerve↗
PubMed1998

Free-flap evolution after hyperthermic regional chemotherapy in the isolated limb for malignant melanoma.

Two patients presenting with a stage I melanoma of the sole of the foot (Clark's level IV, Breslow's 2.8 mm, and Clark's level IV, Breslow's 3.2 mm) underwent a 3-cm tumor free-margin skin resection, followed by microanastomosed muscle flap reconstruction (serratus anterior and latissimus dorsi). Immediately after primary wound healing, an elective inguino-iliac lymph-node dissection, followed by hyperthermic isolated regional chemotherapy with Melphalan, was carried out. Only moderate swelling of both free flaps was observed after these procedures, and this resolved rapidly. The patients returned to ambulation after 2 weeks. No other side effects of the hyperthermic isolated regional chemotherapy were observed in the previously microanastomosed flaps.

Antineoplastic Agents, Alkylating↗
PubMed1997

Cutaneous necrotizing vasculitis after low dose methotrexate therapy for rheumatoid arthritis: a possible manifestation of methotrexate hypersensitivity.

Large haemorrhagic and necrotic cutaneous lesions developed after two low dose (5 mg) methotrexate injections in a patient suffering from long standing rheumatoid arthritis. Differential clinical diagnosis included factitia dermatitis, infectious processes, pyoderma gangrenosum, rheumatoid neutrophilic dermatitis, necrotizing arteritis and vasculitis. Histological and direct immunofluorescent examinations of skin biopsies supported the diagnosis of leucocytoclastic vasculitis. We discuss the respective roles of methotrexate and rheumatoid arthritis in the outbreak of leucocytoclastic vasculitis. Hypersensitivity is strongly suspected.

Antirheumatic Agents↗
PubMed1997

Verrucous carcinoma or epithelioma cuniculatum plantare.

Verrucous carcinoma is a rare form of squamous cell carcinoma. It behaves as a slow-growing, locally aggressive and rarely metastasizing tumour. Three clinical cases are presented, with emphasis on clinical presentation, pathological diagnosis and therapeutic approach. The pathogenesis of verrucous carcinoma, including chronic inflammation and human papillomavirus, is also discussed.

Aged↗
PubMed1997

In vitro characterization of lectin-induced alterations on the proliferative activity of three human melanoma cell lines.

Lectin binding is known to be able to elicit signalling events relevant for various aspects of cell physiology. The influence of lectin binding on melanoma cells remains relatively unexplored. The aim of our study was to investigate the in vitro effects of five plant lectins, namely peanut (PNA), wheat germ (WGA), concanavalin A (Con-A), Griffonia simplicifolia (GSA-IA4) and Phaseolus vulgaris (PHA-L) agglutinins, on the cell proliferation of melanoma cell lines (SK-MEL-28, HT-144 and C32) cultured in media supplemented with either 10% or 1% fetal calf serum (FCS). Cell proliferation was assessed by means of the tetrazolium derivative reduction (MTT) assay. Four lectin concentrations were tested, namely 0.05, 0.5, 5 and 50 micrograms/ml, in four experimental settings, namely 1, 3, 5 and 7 days after the addition of each lectin to the culture media. Determination of the cell gain compartment (percentage of cells in the S and G2 phases of the cell cycle) was done by means of digital cell image analysis assessed on Feulgen-stained nuclei. Our results demonstrated that of the five lectins under study, four had a globally significant dose-dependent toxic effect on melanoma cell proliferation. The fifth lectin, PNA, had a significant stimulatory effect on the C32 cell line. Low doses of lectins may produce a transient increase in cell proliferation. Increasing the FCS from 1% to 10% in the culture media significantly antagonized lectin-induced toxicity in the three cell lines. The cell kinetics measurements showed that the inhibition of cell growth was merely due to cell death. The present data strongly suggest that some lectins might influence the proliferation of melanoma cells. In addition, because lectins are present in our diet and are able to pass into the systemic circulation, we speculate that lectins may exert an influence on melanoma growth under clinical conditions.

Cell Division↗
PubMed1997

Correlation between gender and cytomorphonuclear characteristics in human melanomas and in vitro evidence of sex steroid-induced modifications in the morphonuclear characteristics of three human melanoma cell lines.

The influence of gonadal steroids on human melanoma still remains a controversial issue. The aim of our study was to investigate whether sex steroids may influence the biological characteristics of human melanoma. Such biological characteristics were monitored at the morphological level by means of computer-assisted microscope analysis of Feulgen-stained nuclei, which provides 28 quantitative variables describing the nucleus morphometry (size, anisonucleosis level) and chromatin pattern. This methodology was used to characterize the morphonuclear features in a series of 69 human melanomas (from formalin-fixed paraffin embedded tissues) including 28 male, 17 premenopausal and 24 postmenopausal female patients, and to investigate the effect of two sex steroids (5-alpha-dihydrotestosterone [DHT] and 17-beta-oestradiol [E2]) on three human melanoma in vitro models--the HT-144, SK-MEL-28 and C32 cell lines. The results show that the morphonuclear characteristics of melanoma originating from male and female patients are very distinct (P < 0.01). This difference is still more marked (P < 0.0005) when only premenopausal female patients are compared with male patients. The in vitro data show that both DHT and E2 are able to modify markedly (P < 0.001 to P < 0.0001) the nucleus morphometry and chromatin pattern of the three cell lines. Although the mechanism and the physiological outcome are still unknown, the present work shows that there is in vivo and in vitro evidence that the biological behaviour of human melanoma is influenced by sex steroids.

Adult↗
PubMed1997

Characterization of the nuclear deoxyribonucleic acid content and nuclear morphometry in 71 primary cutaneous melanomas.

BACKGROUND: While the determination of nuclear deoxyribonucleic acid (DNA) content (DNA ploidy level) and nuclear morphometry characterization has proved to be of prognostic value in melanocytic lesions, there are several ways of performing these determinations. OBJECTIVE: To identify which of 9 DNA ploidy- and 2 nuclear morphometry-related variables are of prognostic and/or diagnostic value in 71 primary melanomas. METHODS: Histological typing, Breslow depth determination, the evaluation of Clark's level of invasion and the 11 quantitative variables (calculated in Feulgen-stained nuclei using computer-assisted microscope analysis) determined for each melanoma were submitted to discriminant analysis. RESULTS: The discriminant analysis of image cytometric variables enabled specific cell subpopulations to be identified in histological and the Breslow-related groups, but not in the Clark-related ones. CONCLUSION: The characterization of melanoma heterogeneity by means of the identification of specific DNA ploidy level-related cell subpopulations in specific Breslow-related groups enables the problem of intra- and interobserver variability in Breslow depth determination to be reduced and therefore can help dermatologists in their daily routine.

Adult↗
PubMed1997

Contribution of quantitative lectin histochemistry to characterizing well-differentiated, dedifferentiated and poorly differentiated liposarcomas.

OBJECTIVE: To find new diagnostic markers in the group of lipomatous tumors. STUDY DESIGN: The histochemical lectin staining pattern was characterized in a series of 45 lipomatous lesions, including 10 typical lipomas, 6 atypical lipomas, 8 well-differentiated, 6 myxoid, 5 dedifferentiated and 10 pleomorphic liposarcomas. Three lectins were used-peanut (Arachis hypogaea) agglutinin, which binds to terminal Gal(beta 1,3)GalNAc residues; wheat germ (Triticum vulgare) agglutinin (s-WGA, the succinylated form of WGA), which binds to ((1-4)-D-GlcNAc)n and Neu5NAc residues; and jack bean (Concanavalia ensiformis) agglutinin which binds to alpha-D-Man and alpha-D-Glc residues. Histochemical staining was quantitatively measured by means of a cell image processor. RESULTS: In the case of certain carbohydrate residues, typical lipomas closely resemble atypical lipomas, which in turn closely resemble well-differentiated liposarcomas; typical lipomas differ significantly from well-differentiated liposarcomas. This indicates that atypical lipomas, or at least some of them, could represent a biologic link between typical lipomas and well-differentiated liposarcomas. While well-differentiated and pleomorphic liposarcomas differed significantly from each other, the poorly differentiated component of dedifferentiated liposarcomas included histochemical lectin properties, which were common to both well-differentiated and pleomorphic liposarcomas. CONCLUSION: Some atypical lipomas exhibit glycohistochemical characteristics that are common to those of well-differentiated liposarcoma. The poorly differentiated component of dedifferentiated liposarcomas remains more differentiated in terms of glycohistochemical markers than do poorly differentiated pleomorphic liposarcomas.

Adult↗
PubMed1997

[Surgical closure of leg ulcers].

Surgical closure of leg ulcers has to be preceded by treatment of their etiologies in order to avoid recurrences. Best coverage technique is achieved with the use of a meshed split thickness skin graft, harvested with a dermatoma. Skin graft take depends on the vascular quality of the recipient bed, on the technique used and also on the post-operative care.

Humans↗
PubMed1997

[Pressure sores: management and treatment].

The global management of pressure sores is best ensured with a multidisciplinary approach. We present the experience of the "Groupe de Travail Escarres" (Pressure Sore Workgroup) which gathers physicians and nurses interested with this pathology. The majority of the decubitus ulcers will heal spontaneously with a conservative treatment only. This treatment typically aims at relieving the causes that lead to pressure sores, at eliminating the necrotic tissues, at obtaining favourable local conditions to allow wound healing and at controlling the health status of the patient. Surgical treatment of pressure sores is indicated when wound healing does not occur and when the health status of the patient is sufficiently good. Defect coverage is best carried out using myocutaneous flaps since their excellent blood supply allows a good cleansing of the wound.

Health Status↗
PubMed1996

Methodological aspects of using decision trees to characterise leiomyomatous tumors.

The aim of the present work is to present the potential uses of a classification technique labeled the "decision tree" for tumor characterisation when faced with a large number of features. The decision tree technique enables multifeature logical classification rules to be produced by determining discriminatory values for each feature selected. In this report, we propose a methodology that used decision trees to compare and evaluate the information contributed by different types of features for tumor characterisation. This methodology is able to produce a set of hypotheses related to a diagnosis and or prognosis problem. For example, hypotheses can be producted (on the basis of a set of descriptive features) to explain why tumor cases belong to a given histopathological group. To illustrate our purpose, this methodology was applied to the difficult problem of leiomyomatous tumour diagnosis. The aim was to illustrate what kind of diagnostic information can be extracted from a sample data set including 23 smooth muscle tumors (14 benign leiomyomas and 9 malignant leiomyosarcomas) described by a large set of computer-assisted, microscope-generated features. Three groups of features were used relating to: (1) ploidy level determination (10 features), (2) quantitative chromatin pattern description (15 features), and (3) immunohistochemically related antigen specificities (6 features). All these features were quantified by digital cell image analysis. The results suggest that an objective distinction between leiomyomas and leiomyosarcomas can be established by means of simple logical rules depending on only a few features among which the immunohistochemically revealed antigen expression of desmin plays a preponderant part. One of the combinations of features proposed by the methodology is interesting for pathologists, because it includes two features describing the appearance of a nucleus in terms of chromatin distribution homogeneity and density, two features widely used by pathologists in tumor-grading systems.

Adolescent↗