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Biomedical subjects

G Bruno

Publications and source records attributed to G Bruno.

At least 73 records · Page 4Linked to original sources
PubMed1998

Autoimmune T-cell response to the CD4 molecule in HIV-infected patients.

In a previous study, we demonstrated that by downregulating plasma membrane CD4 and increasing its processing, human immunodeficiency (HIV)-1-gp120 unveils hidden CD4 epitopes, inducing an in vitro anti-CD4-specific T-cell response. We report herein that this mechanism may potentially have important implications in HIV immunopathogenesis, because it could take part in the severe depletion of CD4+ cells that characterizes acquired immune deficiency syndrome (AIDS) and be related to disease progression. Freshly isolated peripheral blood lymphocytes (PBMC) from about 1/4 of a conspicuous cohort of HIV-infected patients responded to CD4 and this response was correlated with beta2-microglobulin levels, widely recognized as marker for progression of HIV infection. Moreover, we provide evidence that a CD4-specific T cell priming can occur in vivo, following a gp120 or anti-CD4 monoclonal antibody (mAb)-mediated CD4 molecule downregulation on antigen-presenting cells (APC). To our knowledge, this is the first study indicating that an autoimmune T-cell response is linked to HIV infection and that it could have an important impact on the immunopathogenesis of this disease.

Adult↗
PubMed1998

Soy protein for the prevention and treatment of children with cow-milk allergy.

Soy-protein formulas are widely used for feeding babies with cow-milk allergy. When they first were marketed, these formulas were the only available cow-milk substitute and they ensured a normal life for many children who were affected by the large spectrum of clinical manifestations of cow-milk allergy. Soy-protein formulas were also given to allergy-prone infants for the prevention of atopic diseases when breast milk was not available. Several researchers studied the prevalence of soy sensitization in allergic disease. Few studies used a challenge test for the diagnosis of soy allergy, even those in patients in whom soy allergy was suspected. In most studies the diagnosis of soy allergy was based on anecdotal case histories reported by parents and was not substantiated by scientific diagnostic criteria: no challenge test to soy was made nor were data available on specific immunoglobulin E to soy. In this paper we critically reviewed literature on the safety of feeding soy-protein formulas to babies with cow-milk allergy as well as on the prevention of cow-milk allergy.

Animals↗
PubMed1998

Effectiveness of a home-made meat based formula (the Rezza-Cardi diet) as a diagnostic tool in children with food-induced atopic dermatitis.

The aim of this study was to investigate the effectiveness of a home-made meat based formula (the Rezza-Cardi diet), as a diagnostic tool for children with atopic dermatitis and suspected multiple food hypersensitivity. Severity scores for atopic dermatitis, body weight and serum lipid profile were evaluated at baseline and four weeks following the feeding with the home-made meat based formula in 16 children with atopic dermatitis and suspected multiple food hypersensitivity. The severity score of the skin lesions improved considerably in all the children; no significant difference was observed in the serum lipid levels before and after one month following the feeding with the home-made meat based formula. All children gained weight according to the Italian Standards. The results of this study indicate that the home-made meat based formula is a useful elimination diet in children with atopic dermatitis and suspected multiple food hypersensitivity.

Child, Preschool↗
PubMed1998

Identification of a serum gelatinase associated with the occurrence of cerebral aneurysms as pro-matrix metalloproteinase-2.

BACKGROUND AND PURPOSE: Subarachnoid hemorrhage from intracranial aneurysm rupture produces a severe form of stroke. Extracellular matrix remodeling is associated with cerebral aneurysms and may play a role in the formation or rupture of these lesions. We previously reported a 3-fold increase in a 72-kDa serum gelatinase in a subgroup of aneurysm patients. The purpose of the present study was to further characterize and identify this gelatinase. METHODS: Serum samples were collected from surgical patients with intracranial aneurysms. The following series of experiments was designed to further characterize and identify the predominant serum gelatinase found in the subgroup of patients with increased gelatinase activity. Gelatin zymography was performed on native serum samples and compared with serum that had been pretreated with a known metalloproteinase activator (4-aminophenylmercuric acetate [APMA]). Gelatin zymography was repeated in the presence of a matrix metalloproteinase (MMP) inhibitor (EDTA) and a serine proteinase inhibitor (phenylmethylsulfonyl fluoride [PMSF]). Final identification was made by Western blotting with the use of monoclonal antibodies to MMP-2 and MMP-9. RESULTS: A consistent gelatinolytic band (72 kDa) was identified in all serum samples (n = 60). Pretreatment of the serum by APMA (n = 60) lowered the molecular weight of the band to 66 kDa. The band was inhibited by EDTA (n = 10) but not PMSF (n = 10), thus characterizing the circulating 72-kDa gelatinase as an inactive pro-MMP. Western blotting (n=20) identified the 72-kDa band as MMP-2. CONCLUSIONS: These findings confirm that the increased gelatinolytic activity observed in vitro in a subset of cerebral aneurysm patients is due to pro-MMP-2.

Adult↗
PubMed1998

Synthesis, structure and in vitro anti-human immunodeficiency virus activity of novel 3-methyl-1H,3H-thiazolo[3,4-a]benzimidazoles.

A series of novel 1-aryl-3-methyl-1H,3H-thiazolo[3,4-a]benzimidazoles, TBZ analogues, were synthesized and investigated as anti-human immunodeficiency virus (HIV) agents in order to study the effects of structural modifications on antiviral activity and cytotoxicity. They were proved to inhibit significantly HIV-1 replication in vitro without showing inhibitory activity on HIV-2 or simian immunodeficiency virus. Their potency was influenced by the presence of suitable substituents in the phenyl ring at C-1 as well as by their stereochemical characteristics. In fact, the most active compound of the series was the trans-1-(2,6-difluorophenyl)-3-methyl-1H,3H-thiazolo[3,4- a]benzimidazole, in which the butterfly-like conformation is stabilized by two intramolecular hydrogen bonds between the fluorine atoms and H-1 and H-3. This was made possible by the trans arrangement of C-1 and C-3 substituents, as shown by X-ray and NMR analysis.

Anti-HIV Agents↗
PubMed1998

Vascular extracellular matrix remodeling in cerebral aneurysms.

OBJECT: The occurrence of cerebral aneurysms has been linked to alterations in the extracellular matrix and to matrix-degrading proteases. The purpose of the present study was to determine whether active extracellular matrix remodeling occurs within cerebral aneurysms. METHODS: Aneurysm tissue was collected from 23 patients (two of whom had a ruptured aneurysm and 21 of whom had an unruptured aneurysm) and compared with 11 control basilar arteries harvested at autopsy. Active proteinases capable of gelatin lysis were identified by performing in situ zymography in the presence and absence of a metalloproteinase inhibitor (ethylenediamine tetraacetic acid) and a serine proteinase inhibitor (phenylmethylsulfonyl fluoride). Immunohistochemical analysis was used to localize plasmin, tissue-type (t)-plasminogen activator (PA), urokinase-type (u)-PA, membranetype (MT1)-matrix metalloproteinase (MMP), MMP-2, MMP-9, and tenascin. Focal areas of gelatin lysis occurred in most cerebral aneurysm tissue samples (17 of 21), but rarely in control arteries (two of 11) (p = 0.002). Both serine proteinases and MMPs contributed to gelatin lysis; however, the MMPs were the predominant enzyme family. Plasmin (p = 0.04) and MT1-MMP (p = 0.04) were expressed in the aneurysm tissue but were unusual in control tissue. The MMP-2 was also expressed more commonly in aneurysm than in control tissue (p = 0.07). The MMP-9 and t-PA were expressed in both groups; however, different staining patterns were observed between aneurysm and control tissue. Tenascin staining was commonly present in both groups, whereas u-PA staining was rarely present. CONCLUSIONS: Aneurysm tissue demonstrates increased proteolytic activity capable of lysing gelatin and increased expression of plasmin, MT1-MMP, and MMP-2 when compared with normal cerebral arteries. This activity may contribute to focal degradation of the vascular extracellular matrix and may be related to aneurysm formation and growth.

Adolescent↗
PubMed1997

Synthesis and characterization in solid and solution of trans-dichloro-1-(2', 6'-difluorophenyl)-1H,3H-thiazolo [3,4-a]-benzimidazole(tri-n-propyl-phosphine)-palladium(II)": a palladium(II) complex of a ligand with anti-HIV properties.

The 1-(2',6'-difluorophenyl)-1H,3H-thiazolo[3,4-a]benzimidazole (L), a highly potent nonnucleoside HIV-1 reverse transcriptase inhibitor, has been reacted with [Pd2Cl4(PPr3n)2] in order to study its coordinating properties towards metal ions. The structure of the synthesized product has been examined in solution by 1H and 13C NMR, and in solid by X-ray analysis. [Pd(PPr3n)(L)Cl2] has a trans structure and L coordinates through imine nitrogen. The loss of anti-HIV properties of L, by complexation, suggests that, unless biological inactivation is simple due to steric reasons, the imine nitrogen atom is an active site of the molecule.

Anti-HIV Agents↗
PubMed1997

Comparison of incidence of insulin-dependent diabetes mellitus in children and young adults in the Province of Turin, Italy, 1984-91. Piedmont Study Group for Diabetes Epidemiology.

To document the incidence of IDDM in the Province of Turin (Italy) in the 8-year period 1984-91 in children (0-14 years) and young adults (15-29 years), in relation to age, sex, monthly-seasonal variability, calendar year and urban/rural area, (all newly diagnosed cases (502) were ascertained through primary and secondary data sources and completeness of ascertainment estimated with the two sample capture-recapture method (99% in childhood and 95% in young adults). The independent effect of age, sex, calendar year, and urban/rural area was estimated with a Poisson regression model. Age-specific incidence rates were 8.42/100,000 (95% CI 7.37-9.62) and 6.72/100,000 (95% CI 5.96-7.58), respectively, in the age groups 0-14 and 15-29 years. Sex differences were evident in young adults, with an almost 1.5-fold increased risk in men (8.37/100,000, 95% CI 7.21-9.71 vs 5.00/100,000, CI 4.09-6.10). Seasonal trend was evident in childhood. Predictors of incidence rates were age, place of residence and interaction between sex and age; no temporal trend was detected. No significant differences were found in the two age-groups with respect to glycaemia, glycosuria, ketonuria, and fasting C-peptide levels. In conclusion, this study shows sex differences in IDDM risk in young adults; 55% of incident cases occurring in young adults; an independent contribution of urban/rural differences to IDDM risk; no temporal trend in 1984-91; a seasonal pattern of incidence in children; no significant differences in clinical presentation between age groups.

Adolescent↗
PubMed1997

Repeated administration of growth hormone-releasing hormone with or without previous administration of pyridostigmine in insulin-dependent diabetes mellitus.

In insulin dependent diabetes mellitus (IDDM) either elevated growth hormone (GH) levels or abnormal responses to specific as well as unspecific stimuli have been reported. As hyperglycemia is known to blunt GH response to various stimuli, a normal GH response to GHRH in presence of hyperglycemia should also be considered inappropriate. To investigate the mechanism underlying this inappropriate GH response, in 9 patients with IDDM, selected for normal GH response to GHRH, we studied the GH response to two consecutive GHRH boluses (1 microgram/kg), the second of which preceded 30 min before by pyridostigmine (120 mg p.o.). Seven age matched normal volunteers were evaluated as control group. Basal plasma glucose and serum GH levels were significantly higher in patients with IDDM than in normal subjects (184.4 +/- 9.6 vs 86.2 +/- 4.4 mg/dl, p < 0.01 and 2.4 +/- 1.0 vs 1.0 +/- 0.4 microgram/l, p < 0.01 respectively). Both in normal subjects and in patients with IDDM the GH response to the second consecutive GHRH administration was lower than that of the first GHRH bolus (delta AUC: 82.5 +/- 28.3 vs 401.1 +/- 131.2 micrograms/l/h, p < 0.05 and 77.2 +/- 30.4 vs 336.8 +/- 60.0 p < 0.02, respectively). Pyridostigmine was able to restore the blunted GH responsiveness to the second GHRH administration in both groups, but this response was found higher in normal than in diabetic subjects (delta AUC: 1250.8 +/- 136.2 vs 527.5 +/- 147.6, p < 0.01). Since the GH-releasing effect of PD is likely to be mediated by the inhibition of hypothalamic somatostatin release, our results suggest that there is also an impaired somatostatin tone in hyperglycemic type 1 diabetic patients with normal GH response to GHRH.

Adult↗
PubMed1997

Effects of antianginal therapy with a calcium antagonist and nitrates on dobutamine-atropine stress echocardiography. Comparison with exercise electrocardiography.

BACKGROUND: Anti-ischaemic therapy with nitrates and/or calcium channel blockers profoundly affects the results of pharmacological stress echocardiography with coronary vasodilators but the influence on catecholamine stress testing remains unsettled. AIMS: The present study aimed to assess the effects of non-beta-blocker antianginal therapy on dobutamine (up to 40 micrograms.kg-1.min-1)-atropine (up to 1 mg) stress. echo-cardiography and to evaluate whether drug-induced changes in the dobutamine atropine stress echocardiography response may predict variations in exercise tolerance. METHODS: Twenty six patients with angiographically assessed coronary artery disease (seven patients with single-, 10 with double-, and nine with triple-vessel disease) performed a dobutamine atropine stress echocardiography and an exercise electrocardiography test in random order both off and on antianginal drugs (nitrates and calcium antagonists). In doubtamine-atropine stress echocardiography, we evaluated: dobutamine time (i.e. the time from initiation of the dobutamine infusion to obvious dyssynergy), wall motion score index (in a 16-segment model of the left ventricle, each segment ranging from 1 = normal, to 4 = dyskinetic), and rate-pressure product at peak stress. RESULTS: Dobutamine-atropine stress echocardiography positivity occurred in 26 out of 26 patients off and in 23 patients on therapy (100 vs 88%, P = ns). Atropine coadministration was needed to evoke echo positivity in no patient off and in five out of 26 on therapy (0 vs 19% P < 0.01). The achieved rate pressure product during dobutamine-atropine stress echocardiography was comparable on and off therapy (17 +/- 4 vs 19 +/- 5 x 10(3) mmHg x heart rate. min-1, P = ns). Therapy induced an increase in dobutamine time (on = 16 +/- 3 vs of = 13 +/- 3 min, P < 0.01) and a decrease in peak wall motion score index (on = 1.3 +/- 0.2 vs off = 1.5 +/- 0.3, P < 0.01). The therapy induced changes in exercise time during the exercise electrocardiography test were not significantly correlated to dobutamine-atropine stress echocardiography variations in either dobutamine time (r = 0.07, P = ns), or peak rate pressure product (r = 0.24, P = ns), or peak wall motion score index (r = 0.02, P = ns). CONCLUSIONS: (1) non-beta-blocker antianginal therapy only modestly reduces dobutamine-atropine stress echocardiography sensitivity, although atropine coadministration is more often required to reach stress echo positivity under therapy; (2) therapy reduces the severity of dobutamine atropine stress echocardiography ischaemia stratified in the time and space domain, but these changes are only poorly correlated to variations in exercise tolerance.

Atropine↗
PubMed1997

Measles vaccine in egg allergic children: poor immunogenicity of the Edmoston-Zagreb strain.

Despite the fact that a number of recent studies have shown that measles/ mumps/rubella vaccine is safe for egg allergic children, many pediatricians are still concerned about immunization in egg allergic children. In Europe, a measles vaccine with the Edmoston-Zagreb strain (EZMV) grown in human fibroblast culture has been developed and recommended for children with egg allergy. However, some doubt arises on the efficacy of this strain due to its weak immunogenicity. The aim of this study was to investigate the immunogenicity of the EZMV in comparison to the measles vaccine with the Schwarz strain (SWMV) grown in a chick embryo fibroblast culture. Thirty-nine children affected by severe immediate manifestations due to IgE mediated egg allergy were enrolled. The children received at random the SWMV (Morupar, Sclavo) or the EZMV (Triviraten, Berna) in one 0.5 ml subcutaneous injection, and were checked for any immediate allergic reactions in the following 4 hours. Blood samples were taken for the detection of specific antibody response 5 months after the immunization. In SWMV seroconverted children (18/19) the geometric mean antibody titer was 3 times higher than that observed in EZMV seroconverted children (17/20) (p < 0.01). No allergic reactions occurred following the immunization with the two different vaccines. This data confirms the safety of SWMV in egg allergic children. In addition, the present study provides further data on the lower immunogenicity of the EZMV in comparison to the SWMV.

Antibodies, Viral↗
PubMed1997

Soy allergy is not common in atopic children: a multicenter study.

The aim of the present study was to evaluate the prevalence of soy allergy (positive skin test and positive challenge test) in a large cohort of atopic children, many of them soy fed early in life for several months. In order to investigate the prevalence of soy allergy, two groups of children were enrolled into the study. The first group comprised a cohort of 505 children with personal history suggestive of food allergy. The second group included 243 children born of atopic parents, who had been soy protein formula fed for the first six months of life for the prevention of cow's milk allergy and who had been prospectively followed up, from birth to 5 years. As regards the prevalence of soy allergy in the cohort of children suffering from allergic disease: 31/505 children (6%) had positive skin prick test to soy, however only six of the 31 children with positive skin prick test to soy had positive challenge test to soy. With regard to the prevalence of soy allergy in the children who had been soy protein formula fed in the first six months of life (second group): 14/243 children (6%) had positive skin prick test to soy, but the double blind placebo control oral food challenge to soy was positive in only one of these 14 children. In conclusion documented soy allergy is not common in atopic children.

Allergens↗
PubMed1997

Effect of pivagabine on stress-induced gastric ulcer formation in rats.

In this study the efficacy of pivagabine (4-[(2,2-dimethyl-1-oxopropyl)amino]butanoic acid, CAS 69542-93-4, Tonerg) in preventing experimental stress ulcer in animals was evaluated. Twenty Wistar rats were randomly subdivided into 2 groups; one group received pivagabine (200 mg/kg orally) and the other tap water. The rats were immobilized in a cold room (2-4 degrees C) for 2 h, and the number and extension of gastric ulcerative and hemorrhagic lesions were evaluated. Pivagabine determined a significant reduction in the number of animals with gastric lesions (5 vs. 10, p < 0.05), in the linear extension of ulcers (2.0 +/- 0.8 vs. 7.2 +/- 1.7 mm, percent protection 72.2, p < 0.05) and in the linear extension of hemorrhages (2.6 +/- 1.0 vs. 10.3 +/- 1.6 mm, percent protection 74.8, p < 0.01). The protective effect of pivagabine on experimental stress-induced ulcers is likely to be mediated by the inhibition of corticotropin releasing factor release from hypothalamus, as also suggested by behavioral studies.

Animals↗