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Biomedical subjects

G Perini

Publications and source records attributed to G Perini.

At least 19 recordsLinked to original sources
PubMed2006

Genome-wide scan supports the existence of a susceptibility locus for schizophrenia and bipolar disorder on chromosome 15q26.

Schizophrenia (SZ) and bipolar disorder (BPD) are two severe psychiatric diseases with a strong genetic component. In agreement with the 'continuum theory', which suggests an overlap between these disorders, the existence of genes that affect simultaneously susceptibility to SZ and BPD has been hypothesized. In this study we performed a 7.5 cM genome scan in a sample of 16 families affected by SZ and BPD, all originating from the same northeast Italian population. Using both parametric and non-parametric analyses we identified linkage peaks on four regions (1p, 1q, 4p and 15q), which were then subjected to a follow-up study with an increased marker density. The strongest linkage was obtained on chromosome 15q26 with a non-parametric linkage of 3.05 for marker D15S1014 (nominal P=0.00197). Interestingly, evidence for linkage with the same marker has been reported previously by an independent study performed on SZ and BPD families from Quebec. In this region, the putative susceptibility gene ST8SIA2 (also known as SIAT8B) was recently associated with SZ in a Japanese sample. However, our allele frequency analyses of the two single-nucleotide polymorphisms (SNPs) with putative functional outcome (rs3759916 and rs3759914) suggest that these polymorphisms are unlikely to be directly involved in SZ in our population. In conclusion, our results support the presence of a gene in 15q26 that influences the susceptibility to both SZ and BPD.

Bipolar Disorder↗
PubMed2006

Altered gene silencing and human diseases.

Epigenetic regulation of gene expression is mediated through several mechanisms, including modifications in DNA methylation, covalent modifications of core nucleosomal histones, rearrangement of histones and RNA interference. It is now clear that deregulation of epigenetic mechanisms cooperates with genetic alterations in the development and progression of several Mendelian disorders. Here, we summarize the recent findings that highlight how certain inherited diseases, such as Rett syndrome, Immunodeficiency-centromeric instability-facial anomalies syndrome, and facioscapulohumeral muscular dystrophy, result from altered gene silencing.

Animals↗
PubMed2004

Health-related quality of life in Italian patients with systemic lupus erythematosus. II. Role of clinical, immunological and psychological determinants.

OBJECTIVE: To investigate the role of clinical, immunological and psychological variables in influencing the health-related quality of life (HRQOL) of Italian patients with systemic lupus erythematosus (SLE). METHODS: The Medical Outcomes Study Short Form-36 was applied in a cohort of 126 SLE patients. At the time of HRQOL testing all patients underwent a clinical and laboratory evaluation, together with the measure of disease activity, severity and damage. In addition, a battery of psychological tests including the Hamilton Anxiety Scale (HAS) and the Hamilton Depression Rating scale (HAM-D) was applied. RESULTS: The parameters which seemed to greatly influence the impairment of HRQOL were older age, arthralgia-arthritis and higher HAS scores as well as HAM-D. In multivariate analysis (adjusted for age), arthralgia-arthritis and a higher HAM-D score were associated with HRQOL impairment. No relationship between HRQOL and SLE activity, severity or damage were found. However, a relationship between HAS or HAM-D scores and damage or arthralgia-arthritis was noted. CONCLUSION: Anxiety, depression and joint pain seem to be the major determinants of HRQOL impairment in SLE patients. Damage seems to influence HRQOL mostly through depression.

Adolescent↗
PubMed2004

Health-related quality of life in Italian patients with systemic lupus erythematosus. I. Relationship between physical and mental dimension and impact of age.

OBJECTIVE: To examine health-related quality of life (HRQOL) in Italian patients with systemic lupus erythematosus (SLE) and compare it with that of healthy people, and to investigate relationships among different dimensions and subscales of a generic health status measure. METHODS: The Medical Outcomes Study Short Form-36 (SF-36) was applied in a cohort of 126 consecutive SLE patients and 96 healthy controls. At the time of HRQOL testing, all patients underwent clinical and laboratory evaluation. RESULTS: Both physical (PCS) and mental (MCS) component summary scores of the SF-36 were reduced in patients compared with controls. In SLE great variability in all the subscales was observed. Significant correlations between PCS and MCS and between many different subscales were observed in patients but not in controls. The PCS was higher than MCS more frequently in controls than in SLE patients (81 vs 48.4%, P<0.00001). In SLE, HRQOL tended to worsen with age. CONCLUSION: Both PCS and MCS contribute to the decrease in HRQOL in SLE patients. In SLE the mutual interaction between these two dimensions seems to be more relevant than in healthy people.

Adolescent↗
PubMed2001

Neurotrophin p75 receptor is involved in neuronal damage by prion peptide-(106-126).

In this work we have investigated the molecular basis of the neuronal damage induced by the prion peptide by searching for a surface receptor whose activation could be the first step of a cascade of events responsible for cell death. By using a human neuroblastoma cell line lacking all the neurotrophin receptors and derived clones expressing the full-length or truncated forms of the low affinity neurotrophin receptor (p75(NTR)), we have been able to demonstrate that the neuronal death induced by the prion protein fragment PrP-(106-126) is an active process mediated by a) the binding of the peptide to the extracellular region of p75(NTR), b) the signaling function of the intracytoplasmic region of the receptor, and c) the activation of caspase-8 and the production of oxidant species.

Binding Sites↗
PubMed2001

Expressing the human genome.

We have searched the human genome for genes encoding new proteins that may be involved in three nuclear gene expression processes: transcription, pre-messenger RNA splicing and polyadenylation. A plethora of potential new factors are implicated by sequence in nuclear gene expression, revealing a substantial but selective increase in complexity compared with Drosophila melanogaster and Caenorhabditis elegans. Although the raw genomic information has limitations, its availability offers new experimental approaches for studying gene expression.

Animals↗
PubMed1999

Profound misregulation of muscle-specific gene expression in facioscapulohumeral muscular dystrophy.

Facioscapulohumeral muscular dystrophy (FSHD) is a neuromuscular disorder characterized by an insidious onset and progressive course. The disease has a frequency of about 1 in 20,000 and is transmitted in an autosomal dominant fashion with almost complete penetrance. Deletion of an integral number of tandemly arrayed 3.3-kb repeat units (D4Z4) on chromosome 4q35 is associated with FSHD but otherwise the molecular basis of the disease and its pathophysiology remain obscure. Comparison of mRNA populations between appropriate cell types can facilitate identification of genes relevant to a particular biological or pathological process. In this report, we have compared mRNA populations of FSHD and normal muscle. Unexpectedly, the dystrophic muscle displayed profound alterations in gene expression characterized by severe underexpression or overexpression of specific mRNAs. Intriguingly, many of the deregulated mRNAs are muscle specific. Our results suggest that a global misregulation of gene expression is the underlying basis for FSHD, distinguishing it from other forms of muscular dystrophy. The experimental approach used here is applicable to any genetic disorder whose pathogenic mechanism is incompletely understood.

Base Sequence↗
PubMed1999

The hepatitis B pX protein promotes dimerization and DNA binding of cellular basic region/leucine zipper proteins by targeting the conserved basic region.

The hepatitis B virus pX protein is a potent transcriptional activator of viral and cellular genes whose mechanism of action is poorly understood. Here we show that pX dramatically stimulates in vitro DNA binding of a variety of cellular proteins that contain basic region/leucine zipper (bZIP) DNA binding domains. The basis for increased DNA binding is a direct interaction between pX and the conserved bZIP basic region, which promotes bZIP dimerization and the increased concentration of the bZIP homodimer then drives the DNA binding reaction. Unexpectedly, we found that the DNA binding specificity of various pX-bZIP complexes differs from one another and from that of the bZIP itself. Thus, through recognition of the conserved basic region, pX promotes dimerization, increases DNA binding, and alters DNA recognition. These properties of pX are remarkably similar to those of the human T-cell lymphotrophic virus type I Tax protein. Although Tax and pX are not homologous, we show that the regions of the two proteins that stimulate bZIP binding contain apparent metal binding sites. Finally, consistent with this in vitro activity, we provide evidence that both Tax and pX activate transcription in vivo, at least in part, by facilitating occupancy of bZIPs on target promoters.

Amino Acid Sequence↗
PubMed1998

[The follow-up of the heart transplant patient].

The authors' purpose is to describe the follow-up of heart-transplant patients after they are released from the heart transplant center and entrusted to their personal physicians and/or to peripheral hospital centers. Three principle periods have been identified. FIRST THREE MONTHS: This period is characterized by a high risk of morbidity and mortality due to the various hemodynamic, immunologic and infectious problems present after transplantation. These problems require careful clinical and laboratory monitoring for diagnostic identification and correct treatment. Because of the complexity of procedures such as endomyocardial biopsy, infusion therapy and incidental pacemaker installation, the patient must be attended to by the heart transplant center. FROM THE THIRD MONTH TO THE FIRST YEAR: This corresponds to the period in which the subject is definitively released from the hospital to his or her own home. The aggressive immunologic action slows down and the first iatrogenic complications arise. Without neglecting the risk of rejection, it is also very important to monitor infectious complications, especially the ones caused by bacterial and/or mycotic agents even after minor incidents. This is particularly true when the patient resumes his own daily and work activity, which must nevertheless be encouraged and aided. The follow-up can be done by peripheral hospital centers, as long as the patients stay in close contact with the transplant center. AFTER THE FIRST YEAR: A satisfactory balance with the cellular immunologic action is achieved and the graft begins to suffer from the slow action of circulating antibodies, whose principle target is the coronary endothelium. Coronary artery disease begins to progress with multiple myocardial ischemic consequences: this represents the chronic rejection phenomenology. There is a further complication in the follow-up of these patients, i.e. the high incidence of neoplasms, particularly lymphomas and skin tumors supported by the immunosuppressive treatment. Together, coronary artery disease and neoplasms represent the most important factors in late mortality (34%).

Biopsy↗
PubMed1997

Plasma interleukin-1 beta and tumor necrosis factor concentrations in obsessive-compulsive disorders.

Plasma interleukin-1 beta (Il-1 beta) and tumor necrosis factor-alpha (TNF-alpha) concentrations were measured twice, at a 48-hour interval, in 27 drug-free obsessive-compulsive patients (12 women and 15 men) and in 27 sex-age-matched healthy controls. Il-1 beta and TNF-alpha concentrations were significantly lower in patients than in controls, whereas there were no differences in either group between men and women, between the samples of the two days, or, in the patients, between those who had and those who had not been previously treated with psychopharmacologic drugs.

Adolescent↗
PubMed1997

A repeated element in the human lamin B2 gene covers most of an intron and reiterates the exon/intron junction.

Nuclear lamins are intermediate filament-type proteins forming a fibrillar meshwork that underlies the inner nuclear membrane. We have previously reported the identification of the human lamin B2 gene that maps to the subtelomeric band p13.3 of chromosome 19 in close proximity of a human DNA replication origin. Here we report the identification within the human lamin B2 gene of a novel repeated element (variable number of tandem repeats: VNTR) that appears to have a very recent origin, being absent in the genome of mouse and primates such as cercopitheques, lemurs and macaques. The VNTR is adjacent to exon 8 of the lamin B2 gene which, albeit encoding the nuclear localization signal of the protein, is highly divergent both at amino acid and nucleotide level among species. Moreover the VNTR, characterized by a repeated unit of about 100 bp, covers most of intron 8 of the gene and reiterates both the last 7 bp of the upstream exon and the exon/intron junction. RT-PCR experiments carried out on HeLa cell RNA suggest that none of the downstream junctions is used during the processing of the lamin B2 pre-mRNA.

Alternative Splicing↗
PubMed1997

Noradrenergic receptor sensitivity in obsessive compulsive disorder: II. Cortisol response to acute clonidine administration.

Sensitivity of pre-synaptic alpha-2- and post-synaptic alpha-1- and beta-adrenoceptors was investigated in 15 patients with obsessive-compulsive disorder (OCD) and in 15 age- and sex-matched healthy controls, by measuring cortisol responses to saline administration and to inhibition by clonidine (clon), a noradrenergic receptor agonist. Basal values of cortisol and responses to administration of saline and of clon were the same in patients and controls.

Adolescent↗
PubMed1997

Noradrenergic receptor sensitivity in obsessive-compulsive disorders: I. Growth hormone response to clonidine stimulation.

In 15 patients with obsessive-compulsive disorder (OCD) and in 15 healthy controls postsynaptic alpha-2-adrenoceptor sensitivity was examined by measuring the growth hormone (GH) response to growth hormone-releasing hormone (GHRH) and to clonidine stimulation. Basal values of GH and somatomedin-C (SMD-C) and mean GH responses to GHRH were the same in patients and controls, thus suggesting that a peripheral pathology of the somatotropic axis should not be present. GH responses to clonidine stimulation were blunted in patients suggesting that post-synaptic alpha-2-adrenoceptors are subsensitive, possibly due to higher than normal noradrenergic secretion.

Adolescent↗
PubMed1997

[Formulation and stability of suspensions for preclinical study].

In preclinical studies, poorly soluble drugs are usually administered orally to experimental animals as suspensions. The present study was aimed at providing data allowing predictive estimations of the stability of such suspensions. To this purpose aqueous suspensions of three drugs (griseofulvin, ibuprofen and indomethacin) were prepared at different concentrations using four different suspending agents: sodium carboxymethylcellulose (CMC), microcrystalline cellulose/carboxymethylcellulose (MC/CMC), hydroxypropylmethylcellulose (HPMC) and jota carragenaan (CJ). The physical and physico-chemical characteristics of the drugs, the rheological properties of the suspending media and of the corresponding drug suspensions, and the physical and chemical stability of the suspensions was then evaluated. The type of suspending agent, rather than the physical characteristics of the drug, appeared to exert the main influence on the physical stability of suspensions. The most stable formulations were produced by suspending agents with low-temperature gelation characteristics (CJ) or with thixotropic flux (MC/CMC).

Chemical Phenomena↗
PubMed1996

Effect of suleparoide on fibrinolysis in the anterior chamber of rabbits.

Intra-ocular fibrin deposition following ocular surgery is a serious postoperative complication. The current management of severe postoperative fibrin response is usually ineffective. A quantitative model of fibrin deposition in the rabbit anterior chamber was used to assess the efficacy of Suleparoide I.N.N. (HHS-5) in preventing fibrin formation and in promoting the clearance of fibrinous membranes. Citrated human plasma was injected intracamerally after paracentesis to induce the formation of fibrin clots: 10 min or 24 h after plasma injection, solutions of HHS-5 at different concentrations were injected into the anterior chamber of rabbits. Intra-ocular HHS-5 injection 10 min after plasma injection prevented the formation of fibrinous membranes in a dose-dependent fashion in almost all treated animals. When HHS-5 was injected at 24 h after fibrin clot formation, a reduction of clot areas was observed but the membranes did not completely disappear. No evidence of ocular toxicity was detected by slit-lamp biomicroscopy, intra-ocular pressure and corneal thickness measurements. On the basis of the results obtained with the present animal model, HHS-5 appears as an effective and safe agent for the prevention of fibrinous membrane formation. The data suggest a potential use of HHS-5 for the prophylaxis of fibrin formation in human eyes undergoing extensive intraocular surgery, or in diabetic patients where a hypercoagulable state may be present.

Analysis of Variance↗