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Biomedical subjects

M Altieri

Publications and source records attributed to M Altieri.

At least 19 recordsLinked to original sources
PubMed2006

Microarray analysis of cultured human brain aggregates following cortisol exposure: implications for cellular functions relevant to mood disorders.

Increased cortisol levels in humans are often observed in patients suffering from mood disorders. In this study human fetal brain aggregates were exposed to cortisol at 500 nM for 3 weeks, as an in-vitro model of chronic cortisol exposure. Microarray analysis on extracted mRNA using the Affymetrix U133A platform was then performed. Our results demonstrated a significant effect of cortisol on 1648 transcripts; 736 up-regulated and 912 down-regulated genes. The most differentially regulated biological categories were: RNA processing, protein metabolism, and cell growth. Within these categories we observed a down-regulation of fibroblast growth factor 2 (FGF2) (-1.5-fold) and aquaporin4 (AQP4) (-1.7-fold), alongside an up-regulation of fibroblast growth factor 9 (FGF9) (+1.7-fold) and vesicle associated membrane protein2 (VAMP2) (+1.7-fold). FGF2, FGF9, AQP4 and VAMP2 changes were confirmed at the protein level by immunohistochemistry. Alterations in FGF transcripts are in keeping with recent literature demonstrating such effects in patients with mood disorders.

Brain↗
PubMed2004

Delayed poststroke dementia: a 4-year follow-up study.

OBJECTIVE: To assess patients who have had a stroke for the subsequent development of poststroke dementia (PSD) and to determine if the characteristics of delayed PSD (dPSD) vary in the long-term follow-up. METHODS: Nondemented patients were followed from 6 months after stroke onset for 4 years. Dementia was diagnosed by International Classification of Diseases-10 criteria; dementia etiology was diagnosed by the National Institute of Neurological and Communication Disorders and Stroke/Alzheimer's Disease and Related Disorders Association and National Institute of Neurologic Disorders and Stroke/Association Internationale pour la Recherche et l'Enseignement en Neurosciences criteria. Neuroimaging and neuropsychological tests were repeated annually. RESULTS: During a 2-year period, 191 stroke patients were enrolled. By the end of the follow-up period, 41 (21.5%) patients had developed dementia. At the Cox regression analysis, dPSD was associated with cortical atrophy (hazard ratio [HR] = 3.4, 95% CI 1.5 to 7.9), age (HR = 3.3, 95% CI 1.4 to 7.8), and multiple ischemic lesions (HR = 2.5, 95% CI 1.2 to 4.8). The Kaplan-Meier analysis showed a significant difference between the incidence of dPSD subtypes (log-rank test; p = 0.002). CONCLUSIONS: During the 4-year follow-up, the incidence of dementia increased gradually, shifting from an Alzheimer disease-type picture in the first years to a vascular dementia type later in years 2 to 4.

Aged↗
PubMed2002

Discontinuous-flow plasmapheresis and patent foramen ovale: a possible cause of paradoxical embolism.

A 68-year-old woman was admitted for a subacute polyradiculoneuropathy and submitted to PE. A central right jugular venous access was placed after the third PE procedure due to a failing peripheral blood access. During the fourth PE, performed with a discontinuous-flow system (continuous-flow used for 3 procedures), she developed multiple embolic ischemic lesions in the left middle cerebral artery (MCA) territory. A thorough cerebrovascular screening showed only a patent foramen ovale (PFO). In our case, a possible increase of the right atrium blood pressure induced by the positive flux of the discontinuous-flow PE could have been responsible for a paradoxical embolism through the PFO. Plasma exchange (PE) is used in several neurologic disorders. It is commonly thought to be a relatively safe procedure. However, a number of adverse events may occur: paradoxical embolism has not been reported to occur.

Aged↗
PubMed2002

SPASE-I: a multicenter observational study on pharmacological treatment of acute stroke in the elderly. The Italian Study of Pharmacological Treatment of Acute Stroke in the Elderly Group.

We investigated the clinical outcome and current therapeutic management of ischemic stroke in elderly patients in different neurological wards throughout Italy. Twelve centers in 10 Italian regions were involved. The clinical and instrumental data were prospectively collected for 335 patients 65 years or older, presenting in a 12-months period. At the multivariate analysis, death was associated with the presence of total anterior circulation infarct and the use of antiedema agents. Stroke-related disability was related to female sex, unified stroke scale (USS) scores at entry and mini-mental state examination (MMSE) scores at the 1-months follow-up. The majority of patients (70%) received antiplatelets to prevent stroke recurrence. Very elderly (> or =80 years) patients had worse presentation and prognosis than less elderly stroke victims (<80 years). Age played an important role in the therapeutic approach to stroke: while antiplatelets were widely used, oral anticoagulants were underused even when specifically indicated.

Age Factors↗
PubMed2001

Vascular dementia: a cognitive SPET-CBF activation study.

OBJECTIVE: We investigated the pattern of regional cerebral blood flow (rCBF) responses to a cognitive task in vascular patients with and without dementia. METHOD: We studied 8 controls and 18 vascular patients by quantitative rCBF assessed by (133)Xe inhalation method and SPET, both at rest and during a cognitive figure recognition task. Eight were mildly demented and 10 were nondemented vascular patients. According to their task performance, 12 patients were classified as 'good performers' (GPs) and 6 patients as 'poor performers' (PPs). RESULTS: Vascular patients activated a larger number of brain areas than controls. No differences were observed between controls, nondemented and mildly demented patients in the pattern of rCBF activation. GPs presented a lower mean percentage of rCBF increase than either controls or PPs. GPs had lower values than PPs in the left temporal, parietal and occipital regions and in the right posterior cingulate and occipital regions. CONCLUSIONS: These data suggest that vascular patients may functionally compensate for vascular damage by activating more brain areas than controls do and, consequently, by increasing the rate of regional activation.

Aged↗
PubMed2001

Usefulness of primitive reflexes in demented and non-demented cerebrovascular patients in daily clinical practice.

The aim of this study was to investigate the usefulness of primitive reflexes (PRs) as additional alert signs in a routine clinical setting of cognitive decline in an elderly population of chronic ischemic cerebrovascular patients. We considered the occurrence of grasp, palmomental, glabellar and snout reflexes in 75 demented (VaD) and 75 non-demented (VaND) patients, and in 75 healthy elderly controls. We never elicited more than two PRs in controls. The occurrence of three or four PRs provided the strongest correlation with dementia (p < 0.0001), with 93% specificity irrespective of low sensitivity. In conclusion, the occurrence of more than two PRs might serve as an additional warning sign of possible mild cognitive impairment in chronic ischemic cerebrovascular patients.

Aged↗
PubMed2000

Do transient ischemic attacks have a neuroprotective effect?

OBJECTIVE: To determine whether TIAs have a neuroprotective effect. BACKGROUND: Ischemic tolerance or preconditioning, which protects the brain against stroke, has been demonstrated in animal models of cerebral ischemia. Because TIA may represent a clinical model of ischemic tolerance, patients with TIA before cerebral infarction (CI) may therefore have a better outcome than patients without TIA before CI. METHODS: A total of 2,490 patients admitted consecutively to a primary care center for first-ever CI in the anterior circulation were divided into two groups on the basis of the presence or absence of prior ipsilateral TIAs. Duration of TIA was classified into three groups (<10 minutes, 10 to 20 minutes, and >20 minutes). The severity of the neurologic picture on admission and functional disability after stroke were compared between patients with and without TIAs. RESULTS: A total of 293 (12%) of the 2,490 patients had prior ipsilateral TIAs before CI. Risk factors did not differ between patients with or without TIAs, whereas the topography and etiology of ischemic stroke did differ (p < 0.001). Patients without prior TIAs had a more severe clinical picture on admission, with a greater reduction of consciousness (p = 0.009). Patients with previous TIAs had a more favorable outcome than those without TIAs (67% versus 58%, p = 0.004). After adjustment for confounding variables, TIAs lasting 10 to 20 minutes were still associated with a favorable outcome (odds ratio, 1.98; 95% confidence interval, 1.27 to 3.08; p = 0.002). The interval between TIA and CI influenced the outcome (p = 0.007). CONCLUSIONS: This study suggests that ischemic tolerance may play a role in patients with ipsilateral TIAs before CI, allowing better recovery from a subsequent ischemic stroke.

Aged↗
PubMed2000

In vivo evidence for the contribution of human histocompatibility leukocyte antigen (HLA)-DQ molecules to the development of diabetes.

Although DQA1*0301/DQB1*0302 is the human histocompatibility leukocyte antigen (HLA) class II gene most commonly associated with human type 1 diabetes, direct in vivo experimental evidence for its diabetogenic role is lacking. Therefore, we generated C57BL/6 transgenic mice that bear this molecule and do not express mouse major histocompatibility complex (MHC) class II molecules (DQ8(+)/mII(-)). They did not develop insulitis or spontaneous diabetes. However, when DQ8(+)/mII(-) mice were bred with C57BL/6 mice expressing costimulatory molecule B7-1 on beta cells (which normally do not develop diabetes), 81% of the DQ8(+)/mII(-)/B7-1(+) mice developed spontaneous diabetes. The diabetes was accompanied by severe insulitis composed of both T cells (CD4(+) and CD8(+)) and B cells. T cells from the diabetic mice secreted large amounts of interferon gamma, but not interleukin 4, in response to DQ8(+) islets and the putative islet autoantigens, insulin and glutamic acid decarboxylase (GAD). Diabetes could also be adoptively transferred to irradiated nondiabetic DQ8(+)/mII(-)/B7-1(+) mice. In striking contrast, none of the transgenic mice in which the diabetes protective allele (DQA1*0103/DQB1*0601, DQ6 for short) was substituted for mouse MHC class II molecules but remained for the expression of B7-1 on pancreatic beta cells (DQ6(+)/mII(-)/B7-1(+)) developed diabetes. Only 7% of DQ(-)/mII(-)/B7-1(+) mice developed diabetes at an older age, and none of the DQ(-)/mII(+)/B7-1(+) mice or DQ8(+)/mII(+)/B7-1(+) mice developed diabetes. In conclusion, substitution of HLA-DQA1*0301/DQB1*0302, but not HLA-DQA1*0103/DQB1*0601, for murine MHC class II provokes autoimmune diabetes in non-diabetes-prone rat insulin promoter (RIP).B7-1 C57BL/6 mice. Our data provide direct in vivo evidence for the diabetogenic effect of this human MHC class II molecule and a unique "humanized" animal model of spontaneous diabetes.

Animals↗
PubMed2000

Bromocriptine and speech therapy in non-fluent chronic aphasia after stroke.

The objectives of this study were to investigate the efficacy of bromocriptine (BR) combined with speech therapy (ST) to improve a late recovery in non-fluent aphasic stroke patients. We performed a double-blind study with high dosage of BR, prescribed according to a dose-escalating protocol, comprehensive of clinical data, relatives' impression, and language evaluations. The study was divided into the following phases: t-0, inclusion; t-30, language re-test to evaluate the stability of aphasia; t-90, placebo (PL) and ST; t-150, BR and ST; t-210, BR; t-270, wash-out. With respect to the baseline assessment, a significant improvement was observed in the following tests: dictation (F, 4.8; p < .004), reading-comprehension (F, 8.1; p < .0003), repetition (F, 3.8; p < .01) and verbal latency (F, 4.9; p < .01). High dosage of BR promoted a late recovery in stable chronic non-fluent aphasia and this improvement was enhanced by combination with ST.

Aged↗
PubMed2000

Comparison between relative dispersion analysis of high-pass resolution perimetry and standard threshold perimetry.

PURPOSE: To evaluate the correlation of the dispersion index (DI) of relative dispersion analysis (RDA), a new high-pass resolution perimetry (HRP) index, with other HRP indices and those of the Humphrey standard threshold perimeter (STP) parameters. METHODS: Sixty-eight eyes were randomly recruited. Thirty-one eyes were classified as glaucomatous (high intraocular pressure, abnormal visual field and/or optic disc) and 37 as ocular hypertensives (high intraocular pressure, normal visual field, normal optic disc). All the subjects were examined with Humphrey Perimeter, program 30-2, and HRP. The HRP data were also analysed with the RDA program. Statistical analysis was performed with Student's t-test, Pearson's r correlation coefficient, Mann-Whitney nonparametric test and Spearman correlation coefficient when appropriate. RESULTS: Within the entire sample significant correlations were found between the RDA index (DI) and all the HRP indices (p < 0.001) and corrected pattern standard deviation (p < 0.01), pattern standard deviation (PSD) (p < 0.01), mean deviation (p < 0.05) and short-term fluctuation (p < 0.05) of STP. A stronger correlation was found in glaucomatous patients. In subjects with ocular hypertension DI was only weakly correlated with PSD, local deviation and form index. No difference in DI was found between glaucoma and ocular hypertension. CONCLUSION: The DI of HRP has the theoretical capacity to detect localised inhomogeneity of retinal sensitivity, but at present our data do not support this hypothesis. Before any clinical applications of this index further studies are needed.

Adult↗
PubMed1999

Correlation between high-pass resolution perimetry and standard threshold perimetry in subjects with glaucoma and ocular hypertension.

PURPOSE: To evaluate the correlation between High-Pass Resolution Perimetry (HRP) and standard threshold perimetry in patients with glaucoma or ocular hypertension. METHODS: 31 glaucomatous patients and 37 ocular hypertension subjects with previous perimetric examination experience were consecutively recruited and only one eye for each patient was selected at random. Glaucomatous patients were classified as having primary open angle glaucoma when they had an abnormal visual field and/or an abnormal optic nerve head (ONH)/retinal nerve fiber layer (RNFL) typical of glaucoma, open angle at gonioscopy and no clinically apparent secondary cause for their glaucoma. Ocular hypertension subjects were defined as having intraocular pressure >21 mm Hg on no treatment, normal visual field, normal ONH and RNFL, elevated intraocular pressure without any treatment. All the subjects were examined with Humphrey Field Analyzer (HFA) 640, 'program central 30-2' (Humphrey Systems, San Leandro, CA, USA) and with High-Pass Resolution Perimeter (HRP), Ophthimus version 2.4,'ring program' (Nikon-HighTech Vision, Goteborg, Sweden). Visual field indices were obtained with both systems: for HFA mean deviation (MD), corrected pattern standard deviation (CPSD) and short term fluctuation (SF), while for HRP global deviation (GD), local deviation (LD), form index (FI) and neural capacity (NC). The data were analyzed by descriptive analysis, Student's t test with Bonferroni's correction or Mann-Whitney non-parametric test and Pearson or Spearman's correlation coefficient. RESULTS: A significant correlation was found between MD and GD (r = -0.81), CPSD and LD (r = 0.87), PSD and LD (r = 0.72). NC was significantly correlated with MD (r = 0.76), GD (r = -0.94). FI was significantly correlated with PSD (r = -0.58), CPSD (r = -0.72), LD (r = -0.56). When the same data were analyzed for the glaucomatous group only, similar results were found; in the ocular hypertensive group no significant correlation was found except between NC and MD (r = 0.52). CONCLUSION: HRP indices vary comparably with HFA indices. Parameters as NC and FI were significantly correlated with standard visual field indices of both HFA and HRP. Although the clinical applications for FI are not clear yet, NC could detect both early glaucomatous damage and age related changes.

Disease Progression↗
PubMed1999

Multiple brain infarcts: clinical and neuroimaging patterns using diffusion-weighted magnetic resonance.

The capability of diffusion-weighted (DW) magnetic resonance imaging (MRI) to identify very early ischemic brain injury better than conventional MRI is well known. This technique, which successfully discriminates acute from old infarcts, is particularly useful in patients with multiple brain infarcts (MBI). Among 142 patients with acute stroke consecutively admitted to our primary care center, we selected 43 patients with two or more brain infarcts on conventional MRI. All patients presented with clinical deficits consistent with acute cerebral ischemia and underwent conventional spin echo for T(1) (T1-WI) and T(2)-weighted images (T2-WI), T(1)-W gadolinium-enhanced images, and echo-planar technique for DW MRI sequences. Patients underwent DW MRI examinations within 15 days of stroke onset (mean +/- SD: 3 +/- 3 days). In all but 1 case, the infarcts detected on DW MRI were also visible on T2-WI. The different signal pattern on DW MRI, compared with T2-WI, facilitated the detection of acute infarcts in all patients. T1-WI with gadolinium enhancement was only helpful in 5 (11.6%) patients. DW MRI enabled precise clinicotopographic correlations in 79% of our patients and provided additional clinically relevant findings in 72% of the patients. Based on the neuroradiological findings, patients were divided into three clinicotopographic types of MBI as follows: 13 patients (30.2%) presented with multiple acute infarcts, 24 patients (55.8%) with a single acute infarct and multiple old infarcts, and 6 patients (13.9%) with multiple acute and old infarcts. In conclusion, DW MRI can easily be added to conventional MRI in order to be able to distinguish acute from old infarcts, and to identify acute multiple lesions. Therefore, a better correlation between clinical symptoms and the site of lesions can be obtained, considerably improving patient care.

Adolescent↗
PubMed1998

Induction of insulitis by glutamic acid decarboxylase peptide-specific and HLA-DQ8-restricted CD4(+) T cells from human DQ transgenic mice.

Insulin-dependent diabetes mellitus in humans is linked with specific HLA class II genes, e.g., HLA-DQA1*0301/ DQB1*0302 (DQ8). To investigate the roles of HLA-DQ8 molecules and glutamic acid decarboxylase (GAD) in disease development, we generated DQ8(+)/I-Abo transgenic mice expressing functional HLA-DQ8 molecules and devoid of endogenous mouse class II. DQ8(+)/I-Abo mice produced antigen-specific antibodies and formed germinal centers after immunization with GAD65 peptides. Two GAD peptide-specific (247-266 and 509-528), DQ8 restricted Th1 CD4(+) T cell lines, were generated from immunized DQ8(+)/I-Abo mice. They induced severe insulitis after adoptive transfer into transgene positive (but not negative) mice who were treated with a very low dose of streptozotocin that alone caused no apparent islet pathology. In addition to CD4, islet mRNA from these mice also showed expression of CD8, IFNgamma, TNFalpha, Fas, and Fas ligand. Our data suggest that a mild islet insult in the presence of HLA-DQ8 bearing antigen-presenting cells promotes infiltration of GAD peptide reactive T cells into the islet.

Animals↗
PubMed1998

GAD-reactive CD4+ Th1 cells induce diabetes in NOD/SCID mice.

Although glutamic acid decarboxylase (GAD) has been implicated in IDDM, there is no direct evidence showing GAD-reactive T cells are diabetogenic in vivo. To address this issue, 3-wk-old NOD mice received two injections of purified rat brain GAD; one mouse rapidly developed diabetes 3 wk later. Splenocytes from this mouse showed a proliferative response to purified GAD, and were used to generate a CD4+ T cell line, designated 5A, that expresses TCRs encoding Vbeta2 and Vbeta12. 5A T cells exhibit a MHC restricted proliferative response to purified GAD, as well as GAD65 peptide 524-543. After antigen-specific stimulation, 5A T cells secrete IFNgamma and TNFalpha/beta, but not IL-4. They are also cytotoxic against NOD-derived hybridoma cells (expressing I-Ag7) that were transfected with rat GAD65, but not nontransfected hybridoma cells. Adoptive transfer of 5A cells into NOD/SCID mice produced insulitis in all mice. Diabetes occurred in 83% of the mice. We conclude that GAD injection in young NOD mice may, in some cases, provoke diabetes due to the activation of diabetogenic T cells reactive to GAD65 peptides. Our data provide direct evidence that GAD65 autoimmunity may be a critical event in the pathogenesis of IDDM.

Adoptive Transfer↗
PubMed1998

Large-scale identification of virulence genes from Streptococcus pneumoniae.

Streptococcus pneumoniae is the major cause of bacterial pneumonia, and it is also responsible for otitis media and meningitis in children. Apart from the capsule, the virulence factors of this pathogen are not completely understood. Recent technical advances in the field of bacterial pathogenesis (in vivo expression technology and signature-tagged mutagenesis [STM]) have allowed a large-scale identification of virulence genes. We have adapted to S. pneumoniae the STM technique, originally used for the discovery of Salmonella genes involved in pathogenicity. A library of pneumococcal chromosomal fragments (400 to 600 bp) was constructed in a suicide plasmid vector carrying unique DNA sequence tags and a chloramphenicol resistance marker. The recent clinical isolate G54 was transformed with this library. Chloramphenicol-resistant mutants were obtained by homologous recombination, resulting in genes inactivated by insertion of the suicide vector carrying a unique tag. In a mouse pneumonia model, 1.250 candidate clones were screened; 200 of these were not recovered from the lungs were therefore considered virulence-attenuated mutants. The regions flanking the chloramphenicol gene of the attenuated mutants were amplified by inverse PCR and sequenced. The sequence analysis showed that the 200 mutants had insertions in 126 different genes that could be grouped in six classes: (i) known pneumococcal virulence genes; (ii) genes involved in metabolic pathways; (iii) genes encoding proteases; (iv) genes coding for ATP binding cassette transporters; (v) genes encoding proteins involved in DNA recombination/repair; and (vi) DNA sequences that showed similarity to hypothetical genes with unknown function. To evaluate the virulence attenuation for each mutant, all 126 clones were individually analyzed in a mouse septicemia model. Not all mutants selected in the pneumonia model were confirmed in septicemia, thus indicating the existence of virulence factors specific for pneumonia.

Animals↗