Biomedical subjects

G Pellegrini

Publications and source records attributed to G Pellegrini.

At least 19 recordsLinked to original sources

PubMed1992

The control of polarized integrin topography and the organization of adhesion-related cytoskeleton in normal human keratinocytes depend upon number of passages in culture and ionic environment.

Keratinocyte adhesion to basal lamina and lateral interactions among basal epidermal cells are mediated, besides other molecules, by integrin receptors that are sorted to defined membrane domains. The hemidesmosome-associated integrin alpha 6 beta 4 is sharply localized to the basal surface of basal cells while alpha 2 beta 1 and alpha 3 beta 1 are enriched laterally. This integrin sorting pattern is perfectly reproducible in vitro by cultured keratinocytes and takes place progressively in primary or secondary culture in the presence of 1.8 mM Ca2+. The polarized topography of integrins is gradually lost with higher passage numbers and between passage 5 and passage 7 there is a complete pericellular redistribution of the above integrins. Along with the decreased basal adhesive value of alpha 6 beta 4 there is a marked increase in the number of focal contacts in high-passage keratinocyte colonies. A similar loss of polarized topography of integrins occurs under low-Ca2+ culture conditions. Increasing the number of culture passages beyond the fifth induces the appearance of the fibronectin receptor alpha 5 beta 1 on the surface of keratinocytes, particularly at intercellular junctions and in some focal contacts. The receptor alpha 5 beta 1 is not detectably exposed by low-passage cells. We propose that forcing keratinocytes into more frequent cell cycles by continuous passaging may perturb the polarized topography of integrins and the adhesion mechanisms of keratinocytes. Then, low-passage keratinocytes are, in our opinion, the most reliable in vitro models for studying the physiology of epidermal cells.

Calcium↗

PubMed1992

Congenital myopathy with type 2A muscle fiber uniformity and smallness.

We describe a 12-year-old girl with congenital myopathy. ATPase histochemical reactions and immunocytochemical analysis of muscle fiber-type composition with monoclonal antibodies against slow, fast (2A and 2B) and fetal myosin demonstrate that this congenital disease is characterized by type 2A muscle fiber uniformity and smallness. This is an unusual feature for a congenital myopathy in which the fiber type predominance, when present, is confined to type I.

Biopsy↗

PubMed1992

High-dose intravenous human immunoglobulin in polymyositis resistant to treatment.

Two patients were treated with treatment-resistant polymyositis with intravenous immunoglobulin over four days at a dose of 0.4 g/kg/day. Clinical recovery followed within two months. Serum creatine kinase (CK) activity decreased to normal, and a clear improvement in muscle strength was observed. One patient showed neither clinical relapses nor increase in serum CK activity after 20 months. The other showed a mild increase in serum CK activity after 24 months and was successfully retreated with intravenous immunoglobulin. There were no significant adverse side effects.

Antiviral Agents↗

PubMed1992

Expression, topography, and function of integrin receptors are severely altered in keratinocytes from involved and uninvolved psoriatic skin.

Psoriasis is a hyperproliferative cutaneous disease of unknown etiology and etiopathogenesis. Alteration of keratinocyte adhesiveness to basal lamina has been proposed as the initial disturbance leading to poorly controlled proliferation. Keratinocyte adhesion to basal lamina and lateral interactions among basal epidermal cells are mediated, besides other molecules, by integrin receptors that are segregated to discrete membrane domains. In this paper, the expression and function of integrins in psoriatic keratinocytes were examined, both in vivo and in vitro. We found that: (a) in psoriatic keratinocytes the integrin heterodimers alpha 2 beta 1, alpha 3 beta 1, and alpha 6 beta 4 have lost their polarized distribution on the plasma membrane; (b) the role of these integrins in mediating keratinocyte adhesion in vitro is altered; (c) psoriatic keratinocytes form focal contacts containing both beta 1 and beta 4 integrins. In normal adult keratinocytes the alpha 5 beta 1 fibronectin receptor is poorly expressed and diffusely distributed on the basal keratinocyte plasma membrane and is not organized in defined adhesive structures. In contrast, psoriatic keratinocytes show a clear fibronectin receptor staining in vivo, and organize alpha 5 beta 1 in typical focal contacts in vitro without any obvious increase of its expression and synthesis. These multiple alterations of integrins are also present in uninvolved keratinocytes from psoriatic patients, suggesting a key role for altered integrin-mediated adhesion in the pathogenesis of this disease.

Adult↗

PubMed1992

N-substituted 2-isocyanoarylacetamides with antimicrobial activity.

In this study, N-substituted 2-formylaminoarylacetamides (3) were obtained by the Ugi four-component reaction between isocyanides (1), aldehydes (2), and ammonium formate. The reaction products (3) were dehydrated with POCl3/NEt3 to give the title compounds (4). The structure of the compounds 3 and 4 was confirmed by spectral data and elemental analysis. Tests of antimicrobial activity showed that compounds 4 were ineffective against E. coli and fairly active against K. pneumoniae and S. aureus. A better activity was shown against B. subtilis, but all the tested compounds showed a very good inhibitory effect against C. albicans.

Acetamides↗

PubMed1992

Synthesis of N-substituted isocyanocarboxamides with antimicrobial activity.

The Ugi four-component condensation between isocyanides 1, cycloketones 2, and ammonium formate affords N-substituted formylaminocarboxamides 3 which are dehydrated with POCl3/NEt3 to give the title compounds 4. The structure of the compounds 3 and 4 was confirmed by spectral data and elemental analyses. In vitro tests of antibacterial activity showed that compounds 4 are ineffective against E. coli and fairly active against K. pneumoniae, B. subtilis and S. aureus. A very good antimicotic activity was shown against C. albicans.

Amides↗

PubMed1992

Pulmonary function in childhood connective tissue diseases.

The term connective tissue diseases (CTD) defines a group of illnesses characterized by the presence of immune abnormalities and by widespread inflammation involving various organs and tissues including the lung. These diseases are not frequent in the paediatric age group. Very few data on pulmonary function are available in paediatric CTD. We investigated possible early lung function abnormalities and any likely relationship with clinical activity of the disease in a group of 81 paediatric CTD patients, without clinical or radiological evidence of pulmonary involvement. Measurement of lung volumes and diffusion lung capacity were performed. A sample of 65 subjects, defined as normal on the basis of history and clinical examination, and matched by age and height with the group of patients, was chosen as control group. CTD patients did not show significant deviations from the control distribution with respect to functional residual capacity (FRC) and maximal expiratory flow at 75% of the forced vital capacity (MEF75) values. On the contrary, both vital capacity (VC) and diffusing capacity of the lungs for carbon monoxide (DLCO) were quite impaired in most CTD during the active phase of the disease. Our results show a functional lung impairment in most children with clinically active CTD, even in absence of abnormalities on chest X-ray pictures.

Adolescent↗

PubMed1991

[Apropos of a large parapharyngeal tumor. Imaging and surgery].

Based on the observation of a voluminous neurinoma of the carotid groove and of the posterior subparotid space, the authors highlight the wide range of parapharyngeal tumors and develop the anatomical bases which shed light on the clinical picture and guide the surgeon. The surgical indication must be put forth cautiously, taking into account the evolutive character of the tumor, the dangers it implies particular in Recklinghausen's disease. Modern radiology plays a major role in the diagnosis and treatment by perfectly visualizing the tumor, its vascularization and its relations with the walls and contents of the parapharyngeal spaces. It will supply indispensable information for directing the coordination between the ENT specialist, the vascular surgeon and the neurosurgeon.

Adolescent↗

PubMed1990

Silent cerebral ischemia in patients with chronic atrial fibrillation--a case-control study.

The cerebral CT-scan results of 72 patients with chronic atrial fibrillation (AF) were compared to those of an age- and sex-matched control group, affected by muscle-tensive headache. None of the patients in the study had any neurologic symptoms. All were normal on neurologic examination. Mean age was 68 years in both groups. Patients with atrial fibrillation had a higher prevalence of hypertension, diabetes and hyperlipidemia, although the differences were not significant. Thirty-two patients (44.4%) with AF showed hypodense lesions on cerebral CT-scan, suggestive of small infarcts, whereas this finding was present only in eight control subjects (11.1%) (p less than 0.05). These results confirm in part the observations reported in literature and suggest a more thorough examination of the problem regarding the prophylaxis of thrombo-embolic risk in patients affected by chronic AF.

Aged↗

PubMed1990

Differences in the antigenic expression of immunomodulatory mannoprotein constituents on yeast and mycelial forms of Candida albicans.

The expression of a strongly immunomodulatory mannoprotein complex (GMP) in the different forms of growth of the human commensal and opportunistic pathogen Candida albicans was studied using a monoclonal antibody (mAb AF1) directed against an oligosaccharide epitope of GMP. Immunofluorescence revealed that the surface of the yeast cells was highly reactive with mAb AF1, but that the reactivity was greatly reduced or disappeared during mycelial conversion. This modulation was shared by a number of strains of C. albicans, and was not solely a temperature- or nutrition-dependent phenomenon. Hypha-deficient strains (A12 and CA2) did not show variations of surface fluorescence under environmental conditions which were permissive for hyphal conversion (incubation in N-acetylglucosamine or Lee's medium, at 37 degrees C). GMP extracts from yeast and mycelial forms of the fungus were separated into three chromatographically distinct, high molecular mass mannoprotein fractions (F1, F2 and F3), which were tested individually by indirect ELISA for mAb AF1 recognition. All yeast-derived constituents and two (F2 and F3) of the hyphal mannoproteins were recognized by the mAb. The low or absent reactivity of the F1 constituent from hyphal cells was confirmed by immunoblots. Irrespective of their source (yeast or mycelial), all fractions reacted to a similar extent with a polyclonal anti-Candida serum. Overall, the data suggest changes in epitope specificity and/or confinement of reactive constituents in the inner wall layers as possible mechanisms of modulated expression of mAb AF1-reactive epitope during mycelial conversion.

Agglutination Tests↗

PubMed1990

Antibody reactivity against single stranded DNA of various species in normal children and in children with diffuse connective tissue diseases.

The aim of this work was to study possible differences in the humoral response against autologous and heterologous (bacterial and mammalian) ssDNA in children with diffuse connective tissue diseases (DCTD) compared with age matched controls. We found that IgM anti ssDNA were significantly increased in systemic lupus eritematosus (SLE) and in juvenile arthritis (JA), but not in juvenile dermatomyositis (JDM). IgG anti ssDNA were significantly elevated only in children with SLE. We next evaluated the binding specificity to human and bacterial ssDNA by inhibition assays. We found that SLE and JA sera recognised epitopes shared in common to endogenous and bacterial ssDNA. In contrast, in normal subjects IgG binding to bacterial DNA was not inhibited by human DNA, while IgG anti human ssDNA were cross reactive with the bacterial antigen. These data suggest that natural antibodies (IgM) producing cells are activated in some but not all DCTD, and that normal children have different reactivity against autologous and heterologous ssDNA with respect to SLE and JA patients.

Adolescent↗

PubMed1989

GABAB autoreceptors in rat cortex synaptosomes: response under different depolarizing and ionic conditions.

Rat cerebral cortex synaptosomes prelabeled with [3H]gamma-aminobutyric acid [( 3H]GABA) were exposed in superfusion to various concentrations of KCl (9-50 mM). The evoked release of [3H]GABA reached a plateau at about 35 mM KCl. The K+-induced release was Ca2+-dependent, particularly at the lowest K+ concentrations. The GABAB agonist (-)-baclofen concentration dependently inhibited the release of [3H]GABA evoked by K+; this effect decreased with increasing K+ concentration and disappeared at 35 mM KCl. The GABAA agonist muscimol (1-100 microM) was totally ineffective to inhibit the release of [3H]GABA. Veratrine (1-30 microM) induced the release of [3H]GABA and the effect was tetrodotoxin-sensitive. (-)-Baclofen, but not muscimol, decreased the veratrine-induced [3H]GABA release; the GABAB agonist was particularly effective in presence of low concentrations of veratrine (1-3 microM) but the effect disappeared when 30 microM of the alkaloid was used. The inhibitory effect of (-)-baclofen on the release of [3H]GABA evoked by 15 mM KCl was dependent on the concentration of Ca2+: the effect increased as the concentration of Ca2+ was raised, reaching a plateau at 0.6 mM Ca2+. Exogenous GABA, in presence of the GABA uptake blocker SK & F 89976A, inhibited the release of [3H]GABA evoked by K+; this effect was antagonized by phaclofen. The data support the idea that terminal GABA autoreceptors in the rat cerebral cortex are of the GABAB type.

Animals↗

PubMed1989

Breast carcinoma and plasma 17-beta-estradiol binding.

The data relating to plasma steroid binding and transport (usually measured with dehydrotestosterone) are controversial. The plasma E2 binding of 79 breast carcinoma patients, 19 premenopausal and 60 postmenopausal, were compared to 46 controls, 21 premenopausal and 25 postmenopausal. In this study the authors removed the endogenous steroids with charcoal, incubated the plasma with 17-beta-E2 in non-saturation conditions, and used ammonium sulfate to precipitate the complex. The authors chose 17-beta-E2 as ligand because the plasma steroid binding system has not been shown to be homogeneous and because this binding function may vary independently for the different steroids. In these patients, the E2 binding was significantly (P less than 0.01) increased (85 +/- 11 pg/ml and 73 +/- 13 pg/ml in premenopausal and postmenopausal) compared to the normal controls (59 +/- 7 pg/ml and 58 +/- 5 pg/ml in premenopausal and postmenopausal women. It is still unclear whether this is a primary increase of the binding capacity or a reaction of the host for sequestering excess circulating E2. However, the small percentage of false-positives and false-negatives suggests that E2 binding could be used as a tumor marker in breast carcinoma.

Breast Neoplasms↗

PubMed1989

Ultrastructural localization of calcium binding sites on human muscle cell surface.

Calcium (Ca2+) is mainly bound to anionic phospholipids and to sialic acid at the cell surface. We studied the ultrastructural localization of these Ca2+ binding sites in normal human muscle fibers, using Polymyxin B as a marker for anionic phospholipids and the lectin Limulus Polyphemus as a probe for sialic acid. We found that anionic phospholipids have a patchy distribution along the muscle sarcolemma, with a preferential localization at the I band level and at the junction between the I and A band. Sialic acid has an uniform distribution along the muscle plasma membrane and basal lamina. Our observations suggest that the plasma membrane, basal lamina, and transverse tubular system play an important role in providing the negative charge of the human muscle cell surface and that these structures may be involved in the binding of calcium.

Arthropod Proteins↗

PubMed1989

A novel type of GABA receptor in rat spinal cord?

The depolarization-evoked release of gamma-aminobutyric acid (GABA) and its possible modulation mediated by autoreceptors were studied in nerve endings isolated from rat spinal cord and prelabeled with the radioactive aminoacid. In the presence of the GABA uptake inhibitor SK&F 89976A [N-(4,4-diphenyl-3-butenyl)-nipecotic acid], used to minimize carrier-mediated homoexchange, exogenous GABA (1-10 mumol/l) decreased in a concentration-dependent way the release of 3H-GABA evoked by 15 mmol/l KCl. The GABAA receptor agonist muscimol (10-100 mumol/l) did not affect the K+ (15 mmol/l)-evoked 3H-GABA release. Similarly ineffective was the GABAB receptor agonist (-)-baclofen (3-100 mumol/l). The effect of GABA was not counteracted by the GABAA receptor antagonists bicuculline,picrotoxin or SR95531 [2-(3'-carbethoxy-2'-propenyl)-3-amino-6-paramethoxy-phenyl-pyr idazinium bromide].(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1989

Cytochrome c oxidase during human fetal development.

Histochemical, biochemical and immunologic analysis of cytochrome c oxidase (COX) in skeletal muscle, heart and kidney during human fetal development was performed. COX histochemical activity was present only in few muscle fibres from the 11th to the 20th week of gestation. At the same developmental stage intrafusal muscle fibres, heart and kidney already showed strong activity. At the 28th week of gestation muscular COX activity was present in about 90% of the fibres. Tissue biochemical analysis confirmed these histochemical findings. Histochemical and biochemical findings compared to the immunocytochemical results and ELISA indicate that COX activity parallels the progressive synthesis of the enzyme in each tissue.

Electron Transport Complex IV↗

PubMed1989

Release-regulating autoreceptors of the GABAB-type in human cerebral cortex.

1. The depolarization-evoked release of gamma-aminobutyric acid (GABA) and its modulation mediated by autoreceptors were investigated in superfused synaptosomes prepared from fresh human cerebral cortex. 2. The release of [3H]-GABA provoked by 15 mM K+ from human cortex nerve endings was almost totally (85%) calcium-dependent. 3. In the presence of the GABA uptake inhibitor SK&F 89976A (N-(4,4-diphenyl-3-butenyl)-nipecotic acid), added to prevent carrier-mediated homoexchange, GABA (1-10 microM) decreased in a concentration-dependent manner the K+-evoked release of [3H]-GABA. The effect of GABA was mimicked by the GABAB receptor agonist (-)-baclofen (1-100 microM) but not by the GABAA receptor agonist muscimol (1-100 microM). Moreover, the GABA-induced inhibition of [3H]-GABA release was not affected by two GABAA receptor antagonists, bicuculline or SR 95531 (2-(3'-carbethoxy-2'-propenyl)-3-amino-6-paramethoxy-phenyl-pyr idazinium bromide). 4. (-)-Baclofen also inhibited the depolarization-evoked release of endogenous GABA from human cortical synaptosomes. 5. It is concluded that GABA autoreceptors regulating the release of both newly taken up and endogenous GABA are present in human brain and appear to belong to the GABAB subtype.

Aged↗

PubMed1988

Hypoglycorrhachia in leptomeningeal carcinomatosis. A pathophysiological study.

We describe a patient with leptomeningeal carcinomatosis in whom no primary malignancy was found in spite of extensive laboratory investigations. The diagnosis was supported, however, by cytological and biochemical CSF examination. Of particular interest in this setting was the low level of glycorrhachia. In order to understand better the mechanism of hypoglycorrhachia, the patient was subjected to I.V. glucose loading; serial samples of blood and CSF were obtained to determine glucose and lactic acid levels. We found that: 1) The low CSF glucose concentration was not increased by I.V. infusion of sugar; 2) the high basal CSF lactic acid level was not further stimulated by I.V. glucose loading. These data suggest that hypoglycorrhachia was not due to an increased utilization of glucose by neoplastic cells that infiltrate the meninges but to abnormal transport of glucose from blood to CSF.

Carcinoma↗