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Biomedical subjects

E De Angelis

Publications and source records attributed to E De Angelis.

At least 19 recordsLinked to original sources

Cis and trans interactions of L1 with neuropilin-1 control axonal responses to semaphorin 3A.

Mutations in the L1 gene induce a spectrum of human neurological disorders due to abnormal development of several brain structures and fiber tracts. Among its binding partners, L1 immunoglobulin superfamily adhesion molecule (Ig CAM) associates with neuropilin-1 (NP-1) to form a semaphorin3A (Sema3A) receptor and soluble L1 converts Sema3A-induced axonal repulsion into attraction. Using L1 constructs containing missense pathological mutations, we show here that this reversion is initiated by a specific trans binding of L1 to NP-1, but not to L1 or other Ig CAMs, and leads to activation of the NO/cGMP pathway. We identified the L1-NP-1-binding site in a restricted sequence of L1 Ig domain 1, as a peptide derived from this region could reverse Sema3A repulsive effects. A pathological L1 missense mutation located in this sequence specifically disrupts both L1-NP-1 complex formation and Sema3A reversion, suggesting that the cross-talk between L1 and Sema3A might participate in human brain development.

Animals↗

Alternative use of a mini exon of the L1 gene affects L1 binding to neural ligands.

Neural cell adhesion molecule L1 is a cell surface glycoprotein required for the correct development of the nervous system. L1 exists as two isoforms encoded by mRNA species that either collectively incorporate or exclude exons 2 and 27. Neurons utilize only the full-length isoform, whereas Schwann cells, kidney cells, and blood lymphocytes only express the short form of L1. Still other cells, oligodendrocytes, regulate L1 isoform expression in a maturation-dependent manner. The RSLE motif encoded by exon 27 is known to have a role in clathrin-mediated endocytosis of L1, but the function of the exon 2-encoded motif (YEGHHV) is unknown. Here we show that this motif is required for the optimal binding of L1 to several neural ligands and is likely to be important for nervous system development. Thus, alternative use of exon 2 is a mechanism for regulating ligand interactions with L1.

Alternative Splicing↗

Neural cell recognition molecule L1: relating biological complexity to human disease mutations.

Human single gene disorders that affect the nervous system provide a host of natural mutations that can be deployed in the quest to understand its development and function. A paradigm for this approach is the study of disorders caused by mutations in the gene for the neural cell recognition molecule L1. L1 is the founder member of a subfamily of cell adhesion molecules that are primarily expressed in the nervous system, and to date it is the only one to be associated with a hereditary disease. In this review we will summarize how the analysis of pathological mutations in L1 is complementing the study of mouse models and in vitro analysis of L1 function.

Animals↗

Role of the macrophage galactose lectin in the uptake of desialylated LDL.

Desialylated low density lipoprotein (LDL) is rapidly taken up and accumulated by both peripheral blood monocytes and cells isolated from human arterial intima consisting predominantly of smooth muscle cells. It is shown that thioglycollate (TG)-elicited mouse macrophages and mouse peritoneal macrophages stimulated with lipopolysaccharide (LPS) show increased expression of a membrane-bound, galactose-specific lectin that could be responsible for this uptake. In LPS-stimulated macrophages accumulation of desialylated LDL is increased ca. 2.6-fold. Accumulation of acetylated LDL in the same cells is reduced, suggesting that the galactose-specific lectin might be responsible for the uptake of desialylated LDL. Transfection of cells with the mouse macrophage Gal/GalNAc-specific lectin (MMGL) increased their capacity to take up asialofetuin (ASF) and, to a smaller extent, desialylated LDL. The uptake of desialylated LDL was small, most likely due to the high k(d) of MMGL for biantennary oligosaccharides as found on LDL, and low concentration of LDL achieved in tissue culture experiments. The data suggest that the expression of galactose-specific lectins can be elevated under inflammatory conditions, and that these receptors could contribute to foam cell formation under conditions of high desialylated LDL concentration, as might be found in arterial intima.

Animals↗

Effectiveness and acceptability of a domiciliary multidrug inhalation treatment in elderly patients with chronic airflow obstruction: metered dose inhaler versus jet nebulizer.

The aim of this study was to compare the immediate and long-term bronchodilator effect as well as the patient acceptability of a 2-week, multidrug, inhalation treatment delivered by a metered dose inhaler (MDI) versus a jet nebulizer in a group of elderly patients with chronic obstructive pulmonary disease (COPD) or asthma and an at least partially reversible airflow obstruction. Twenty elderly outpatients (17 men; mean +/- SD age, 67 +/- 2 years; mean +/- SD baseline forced expiratory volume in 1 second [FEV1], 46.5 +/- 14% of predicted value) with COPD or asthma participated in the study, which was of an open, randomized, crossover design. After a 1-day baseline evaluation, including patient history, clinical examination, and spirometry, participants were randomly assigned to receive a multidrug inhalation treatment (a combination of salbutamol, ipratropium, and flunisolide) with either an MDI or a jet nebulizer. Two weeks later, they were shifted to treatment with the alternative system for a further 2 weeks. FEV1 was measured on the first and fourteenth days of each treatment period, on each occasion both before and 30 minutes after the morning inhalation. At the end of the study, patients were asked to express a personal preference for one of the two inhalation treatments with regard to effectiveness and acceptability by filling out a simple questionnaire. Both the MDI and jet nebulizer had a significant immediate bronchodilator effect on the first and fourteenth days of treatment, with no differences between treatments. No long-term bronchodilator effect was seen with either aerosol delivery system. Patient preferences were clearly in favor of the jet nebulizer with regard to effectiveness and in favor of the MDI with regard to acceptability. In conclusion, in elderly patients with COPD or asthma and partially reversible airflow obstruction, a maintenance multidrug bronchodilator/anti-inflammatory inhalation treatment produced a statistically significant and clinically relevant bronchodilator effect without substantial differences between the two delivery systems. Most patients considered the MDI to be more acceptable and the jet nebulizer to be more effective. These preferences should be taken into consideration when prescribing a maintenance aerosol inhalation treatment.

Administration, Inhalation↗

Pathological missense mutations of neural cell adhesion molecule L1 affect homophilic and heterophilic binding activities.

Mutations in the gene for neural cell adhesion molecule L1 (L1CAM) result in a debilitating X-linked congenital disorder of brain development. At the neuronal cell surface L1 may interact with a variety of different molecules including itself and two other CAMs of the immunoglobulin superfamily, axonin-1 and F11. However, whether all of these interactions are relevant to normal or abnormal development has not been determined. Over one-third of patient mutations are single amino acid changes distributed across 10 extracellular L1 domains. We have studied the effects of 12 missense mutations on binding to L1, axonin-1 and F11 and shown for the first time that whereas many mutations affect all three interactions, others affect homophilic or heterophilic binding alone. Patient pathology is therefore due to different types of L1 malfunction. The nature and functional consequence of mutation is also reflected in the severity of the resultant phenotype with structural mutations likely to affect more than one binding activity and result in early mortality. Moreover, the data indicate that several extracellular domains of L1 are required for homophilic and heterophilic interactions.

Animals↗

Prospective evaluation of transabdominal bowel sonography in the diagnosis of intestinal obstruction in Crohn's disease: comparison with plain abdominal film and small bowel enteroclysis.

Transabdominal ultrasonography is a noninvasive, radiation-free method that is well tolerated by patients with acute abdominal symptoms. The aim of this study was to investigate the validity of transabdominal ultrasonography, compared with plain abdominal film and small bowel enteroclysis in the diagnosis of small bowel obstruction in patients with Crohn's disease (CD). Forty-four patients with CD ileitis or ileocolitis and acute obstructive symptoms who received ultrasonography and plain abdominal film at hospital admission were evaluated by small bowel enema before dismissal or surgery and were considered for statistical analysis. Small bowel obstruction was diagnosed by ultrasonography in 23 of 44 patients (52%), by plain abdominal film in 26 of 44 patients (59%), and by small bowel enema in 28 of 44 patients (64%); the diagnostic accuracy of plain abdominal film and ultrasonography compared with small bowel enema was 73% and 89%, respectively. Ultrasonography proved to be highly specific (100%) with no false positive results. Surgery performed in 25 of 44 patients for symptoms refractory to medical treatment confirmed the high diagnostic value of ultrasonography. The result of this study indicates that transabdominal ultrasonography is accurate and highly specific in the diagnosis of small bowel obstruction and can be considered a valuable first choice examination in CD patients with obstructive symptoms.

Adolescent↗

Expression of cripto and amphiregulin in colon mucosa from high risk colon cancer families.

We assessed the expression of the epidermal growth factor (EGF)-related peptides, cripto-I (CR-I) and amphiregulin (AR), in a small panel of human colon adenomas and carcinomas. CR-I immunoreactivity was found in 17/31 (55%) of colon adenomas, and in 33/39 (84%) colon carcinomas. AR immunostaining was observed in 16/26 adenomas (61%) and in 20/26 carcinomas (77%). CR-I and AR staining were also assessed in 29 specimens from 24 individuals that belong to families with high incidence of colorectal carcinoma, and in 5 non-high risk individuals. Expression of CR-I was detected in 18/29 (62%) of high risk colon mucosa specimens, but only in 1/5 (20%) specimens from non-high risk individuals, while AR staining was found in 20/29 (69%) and in 4/5 (80%) of colon mucosa samples from high and low risk individuals, respectively. A majority (21/29; 72%) of the specimens from the high risk individuals had a high proliferative rate, as measured by Ki-67 staining. A statistically significant correlation was found between high proliferative rate, increased expression of CR-I and reduced expression of AR in the mucosa specimens from high risk individuals, suggesting that these might represent early events in colon tumorigenesis.

Adenoma↗

Ultrasonic nebulization of hypertonic solution: a new method for obtaining specimens from nasal mucosa for morphologic and biochemical analysis in allergic rhinitis.

Various techniques are used to collect specimens from the nasal mucosa for morphologic and biochemical analysis. The purpose of this study was to devise a method that overcomes some of the disadvantages (e.g., invasive procedure, samples not suitable for cytologic and biochemical analysis, lack of standardization, and poor reproducibility) of these techniques. The new method requires subjects, with neck extended, to inhale an ultrasonic nebulization of a hypertonic (3% NaCl) solution (UNHS) for 5 min. They then blow their nose into a Petri dish, one nostril at a time with the other one blocked. The secretions are dispersed with 0.1% dithiothreitol in phosphate buffer solution for 20 min. Total cell count (TCC) is evaluated, and the cellular suspension is divided into two aliquots: one is centrifuged and the supernatants are collected for eosinophil cationic protein (ECP) measurements; the other is cytocentrifuged and the slides, stained with Diff-Quik, are used for differential cell count. The results obtained with the UNHS and nasal lavage (NL) methods were compared. Eleven nonatopic healthy subjects and 19 allergic rhinitic patients were studied. Total cell count (x10(5)) was significantly higher with UNHS than with NL (13.0+/-12.3 vs 1.9+/-1.6; P<0.01) The differential cell count was similar with the two procedures. ECP levels (microg/l) were higher with UNHS than with NL (39.1+/-38.2 vs 16.7+/-41.2; P<0.01). For evaluation of reproducibility, four healthy and six rhinitic subjects underwent UNHS on two occasions within 5 days, and the results of two samples (sample 1 vs sample 2) were analyzed. Reproducibility was good as to TCC, differential cell count, and ECP.

Adult↗

[Cervical lymphangioma in the adult: a report of a significant case].

UNLABELLED: Lymphangioma in the adult is quite rare: the most common localization in the head and neck region is at the posterior triangle of the cervical lateral region (75%). Moreover, it favors the right latero-cervical area (72%) thus supporting a disembryogenetic pathogenesis. Indeed, according to Dowd and Goetsch, the lymphatic tissues are rearranged in this area, creating the principle head and neck drainage. The presence of disembryogenetic alterations in the lymphatic architecture could go on unnoticed until the lymphatic circulation equilibrium is altered by some anatomo-functional event compromising the involved area. CLINICAL CASE: G.P., a 41-year-old male, presented a swelling in the right submandibular region since approximately 4 months and which had increased in size over the last 30 days. The case history revealed that, at the age of 18 he had been admitted to the hospital for surgical removal of an angiomatose phlegmonous neoformation while, at the age of 18 38, he had undergone surgery for a lipoma in the right temporo-zigomatic area. Head and neck CT using a contrast medium revealed a formation of mixed density, predominantly liquid, apparently multiloculated. The patient underwent surgery, via a right submandibular cervicotomy approach, to remove the cystic neoformation and attached submandibular gland. In addition, the plurilobate mass showed submentonier, parapharyngeal, subdigastric and subhyoid extensions. Histology led to a diagnosis of "cystic lymphangioma". The clinical case reported is quite unusual in that:--the submandibular (anterior triangle) location is rare, accounting for only 6.25% of the cervical manifestations;--the previous case history of this patient underlines the importance of an embryogenic alteration in the regional lymph network;--this condition, clinically manifest in infancy as a submandibular (angiomatose) phlegmon became latent in adulthood after surgery for right temporo-zigomatic lipoma. In light of the above data, it can be hypothesized that a disembryogenetic origin of the adult lymphangioma, associated with a predisposition (scarred areas further compromising the lymph vessel architecture) and some precipitating event (surgical trauma in adulthood), have lead to delayed development of the amartoma.

Adult↗

[The conjoined twins born in Valdarno al Terraio].

Surgical pre and post-operative problems involving the separation of conjoined twins of ischiopagus type make actual the interpretation of a relief coming from the Hospital of Santa Maria della Scala in Florence and dating probably from XIVth century. The work has been sculptured after the death of a couple of ischiopagus twins in the same Hospital in 1316. Their birth is registered in Giovanni Villani's Cronaca and in Petrarca's Rerum Memorandarum Libri.

Abnormalities, Multiple↗

[Giant cervical hyperostosis of the prevertebral space: presentation of two cases and review of the literature].

Swellings of the retropharyngeal area are quite rare and all cases have common symptoms deriving from the site of origin, size, interaction with the surrounding anatomical structures and the presence, or lack thereof, of any associated inflammation. The main symptoms are dysphagia, the feeling of a foreign body in the pharynx and dyspnea. The present work describes two clinical cases of hyperostosis of the cervical column both of which presented discrete dysphagia, intermittent dyspnea and swelling in the area located between the pharynx and the spinal column thus leading to the feeling of having a foreign body in the area. The first case was a hyperostosis of the prevertebral space located on the right side and running medially toward the homolateral palatine tonsil. The pharyngoepiglottic fold area was medialized while the glottic region appeared normal. The second case had an ovoid median swelling in the hypopharynx stemming from the prevertebral space. During normal respiration the upper part of the laryngeal face of the epiglottis came into contact with this swelling while during phonation the glottic plane was normal. CT, MRI and endoscopy all proved able to provide information regarding the anatomy of the neoformation and the relationship with the neighboring structures. Many surgical techniques have been described to gain access to the spinal column osteophytes. The transcervical techniques give better exposure than transoral approaches although they increase the risk of damaging the recurrent laryngeal nerve and the sympathetic nervous system; moreover they require marked retraction of the carotid artery. In the authors' experience surgery was opted for in only one of the cases as the patient was relatively young and in good general health. The transcervical posterolateral approach was chosen as it provided better exposure of the cervical region between C3 and C6 than did the anterolateral approach.

Aged↗

Adaptive cellular response to osmotic stress in pig articular chondrocytes.

The authors studied the effects of a wide range of medium osmolarities (from 0.28 osM (physiological osmolarity of plasma and synovial fluid) to 0.58 osM) by altering Na+ concentration in high density cultures of pig articular chondrocytes in order to analyze the behaviour of some functional and structural parameters during cell adaptation to these imposed changes in the ionic environment. Biochemical and morphological results indicated that, even if isolated from the tissue matrix and cultured in vitro, chondrocytes maintained active osmoregulation systems which are present in living conditions. They showed a similar biochemical and morphological behavior when cultured at 0.28 osM and 0.38 osM but they were able, with regard to protein synthesis, aminoacid transport and proliferation rates, to respond quickly and to adapt to 0.48 osM medium as well. On the contrary, the treatment at the highest osmolarity (0.58 osM) early altered these biochemical parameters and was detrimental or even gave rise to lethal damage during long-term treatment. Furthermore, while chondrocytes cultured in 0.28-0.38 osM medium maintained phenotypic characteristics in culture, the higher osmolarities (0.48-0.58 osM) caused morphological changes in cell populations resulting in loss of phenotypic cell stability as demonstrated by their taking on a fibroblast-like shape as well as a lack of ability to assembly matrix proteoglycans.

Adaptation, Physiological↗

Osmotically inducible uptake of betaine via amino acid transport system A in SV-3T3 cells.

The osmotically inducible uptake of betaine (NNN-trimethylglycine) by SV-3T3 cells has been studied and compared with the similar process in MDCK cells. Betaine uptake by SV-3T3 cells could be described in terms of a saturable, Na(+)-dependent, component plus a small non-saturable, Na(+)-independent, component. Transport was active, producing considerable accumulation of betaine in the cells. After exposure of the cells to hypertonic conditions for 6 h, there was a marked increase in betaine uptake. Kinetic analysis indicated that this increase resulted from an increase in the Vmax. value of the saturable component, from about 88 to 185 nmol of betaine/5 min per mg of protein, the corresponding Km values of about 15 and 10 mM not being significantly different. This induction of transport activity was detectable only after about 2 h exposure of the cells to hypertonic medium, closely paralleling an induction of influx of N-methylaminoisobutyric acid, and was prevented by the presence of cycloheximide. Betaine influx was markedly inhibited by several neutral amino acids, particularly those transported by system A, such as N-methylaminoisobutyric acid and the imino acid proline. A high concentration (25 mM) of betaine also significantly inhibited the uptake of proline by SV-3T3 cells. Although very similar results were obtained with MDCK cells, prolonged exposure of cells to hypertonic conditions revealed distinct differences. When the hypertonic incubation was extended from 6 h to 24 h, betaine transport in SV-3T3 cells either remained the same or decreased, whereas it showed a further marked increase in MDCK cells, and also became sensitive to inhibition by gamma-aminobutyric acid. mRNA for the betaine transporter BGT-1 [Yamauchi, Uchida, Kwon, Preston, Brooks Robey, Garcia-Perez, Burg and Handler (1992) J. Biol. Chem. 267, 649-652] was detectable in MDCK cells exposed to hypertonic medium for 24 h, but not in SV-3T3 cells under any conditions. It is concluded that SV-3T3 cells do not produce a specific inducible transporter analogous to BGT-1, but they can accumulate betaine via the amino acid transport system A.

3T3 Cells↗

Different HSP70 expression and cell survival during adaptive responses of 3T3 and transformed 3T3 cells to osmotic stress.

Responses both to hyperosmotic stress and to heat shock were compared in 3T3 cells, spontaneously transformed cells (ST3T3) and simian virus 40-transformed cells (SV3T3). Cell adaptation to these stresses was measured in terms of surviving cell viability and plating efficiency, while their induced synthesis of stress proteins was monitored in terms of the presence of mRNA for HSP70, the pattern of polypeptides synthesised and the accumulation of HSP70 detectable by monoclonal antibodies. All three types of cells responded similarly to heat shock in their expression of HSP70 and showed no clear differences in ability to recover. In contrast, both ST3T3 and SV3T3 cells adapted more poorly and much more slowly to hyperosmotic stress (0.5 osM incubation) than did normal 3T3 cells. This different pattern of adaptation to hyperosmotic stress was parallelled by the cells' different expression of a stress protein that could not be distinguished from the heat-induced HSP70 by any of the methods listed above. In view of these findings it seems possible that hyperosmotic treatment might be useful in selectively affecting the survival of tumour cells.

3T3 Cells↗

[Not Available].

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Americas↗

[Not Available].

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Greece↗