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S Romeo

Publications and source records attributed to S Romeo.

At least 19 recordsLinked to original sources
PubMed2006

Brachyury and chordoma: the chondroid-chordoid dilemma resolved?

Chordoma, and its relationship to the notochord, has intrigued many researchers over the last two centuries. In particular, the morphological overlap with cartilaginous tumours is striking, and developmental biology has shown a tight relationship between cartilage and the notochord. This is reflected in the expression of common genes in chordoid and chondroid tumours. Wide gene expression analyses have led to the identification of key molecules that might play a crucial role in the pathogenesis of chordoma. Brachyury, a key factor in notochord fate, is significantly differentially expressed in chordoma. This not only gives insight into the histogenesis of this tumour but may also point towards new diagnostic tools in the differential diagnosis between chordoid and chondroid tumours.

Bone Neoplasms↗
PubMed2006

The G972R variant of the insulin receptor substrate-1 gene impairs insulin signaling and cell differentiation in 3T3L1 adipocytes; treatment with a PPARgamma agonist restores normal cell signaling and differentiation.

The insulin receptor substrate-1 (IRS-1) plays a central role in insulin sensitivity, and association studies have shown that the IRS-1 G972R variant is a risk factor for insulin resistance. However, how this mutation may lead to impaired insulin sensitivity is still to be determined. Our study aimed to evaluate, after transfection of the IRS-1 G972R variant in 3T3L1 adipocytes, the effect of this mutation on insulin signaling and on cell differentiation. The 3T3L1 cells were transfected with pcDNA3 expression vector containing either the human wild-type IRS-1 or the G972R variant. After induction of differentiation, the 3T3L1 transfected with wild-type IRS-1 differentiated in 6-8 days, while the cells transfected with G972R variant did not differentiate. To determine whether the defect in IRS-1 was responsible for this, we analyzed the expression of several genes involved in the insulin signaling pathway. Results showed that PPARgamma expression was significantly reduced in cells transfected with the mutated IRS-1, together with a significant decrease in binding of phosphatidylinositol-3 kinase (PI 3-kinase) to IRS-1 G972R and in PI 3-kinase activity. In addition, we observed that the interaction between the insulin receptor (IR) and the IRS-1 G972R protein was increased and that the autophosphorylation of the IR was significantly inhibited in 3T3L1-G972R cells compared with 3T3L1-WT. Treatment of the 3T3L1-G972R cells with pioglitazone (PIO), a PPARgamma agonist, restored differentiation with higher level of PPARgamma expression and restoration of PI 3-kinase binding to IRS-1 G972R and PI 3-kinase activity. IR autophosphorylation was also increased. Withdrawal of PIO in fully differentiated 3T3L1-G972R cells determined the reappearance of the insulin signaling defect. Finally, we observed higher levels of IRS-2 expression, suggesting that IRS-2 may play a more important role in adipocyte insulin signaling. In conclusion, IRS-1 G972R variant impairs insulin signaling, and treatment with PPARgamma agonist restores the normal phenotype of 3T3L1 cells.

3T3 Cells↗
PubMed2005

A structure-activity study for the inhibition of metalloproteinase-9 activity and gene expression by analogues of gallocatechin-3-gallate.

Catechins are able to modulate the gelatinolytic activity of matrix metalloproteinase-9 (MMP-9) by reducing its release from macrophages. Gallocatechins decrease MMP-9 secretion by lowering MMP-9 promoter activity and mRNA levels. The effect appears to be dependent on some structural and stereochemical requirements. In this study, the relationship between chemical structure and activity was studied by testing the effect of analogues of (+/-)-gallocatechin-3-gallate (+/-)-GCG, selectively deprived of hydroxyl groups, on MMP-9 activity, transcription, and secretion. Our results indicate that (+/-)-GCG and (+/-)-catechin-3-gallate are characterized by a substitution pattern compatible with direct inhibition of MMP-9 activity. Conversely, when transcription was the target, (+/-)-trans-3-flavanol-3-benzoate, lacking all the hydroxyl groups, was the most effective both in lowering MMP-9 promoter activity and consequently protein secretion, and in inhibiting nuclear-factor-kappaB-driven transcription. Our results suggest that the structural requirements for enzyme inhibition are different from those necessary for targeting gene expression.

Animals↗
PubMed2004

The mGlu5 metabotropic glutamate receptor is expressed in zones of active neurogenesis of the embryonic and postnatal brain.

Metabotropic glutamate (mGlu) receptors have been implicated in the regulation of developmental plasticity. Here, we examined the expression of mGlu1a-b, -2, -3, -4a-b, and -5a receptor subtypes from embryonic day 12 (E12) to the early and late postnatal life. While all transcripts (with the exception of mGlu4 mRNA) were detected prenatally, only the mGlu5 receptor protein was found in detectable amounts in the embryonic brain. Immunohistochemical analysis showed that the mGlu5 receptor was mainly expressed by cells surrounding the ventricles at E15, whereas it was more diffusely expressed at E18. In the postnatal life, besides its classical expression sites, the mGlu5 receptor was found in zones of active neurogenesis such as the external granular layer (EGL) of the cerebellar cortex and the subventricular zone. In these regions, the presence of actively proliferating progenitor cells was detected by BrdU staining. No other subtype (among those we have examined) was found to be expressed in regions enriched of BrdU(+) cells. These data suggest a role for mGlu5 receptors in the early brain development and in basic cellular processes such as proliferation and/or differentiation.

Animals↗
PubMed2004

Expression of cartilage growth plate signalling molecules in chondroblastoma.

Chondroblastoma (CB) is a rare benign tumour (<1% of all bone tumours) involving epiphyseal long bones (male:female 1.5:1). During development, and in the postnatal period, IHh/PTHrP and FGF signalling molecules control the space and timing of chondrocyte differentiation. Considering the close relationship of CB with the growth plate (age and location), the expression of proteins involved in epiphyseal growth regulation was studied. Twelve cases of CB were retrieved. Immunohistochemistry was performed using antibodies against fibroblast growth factor-2 (FGF-2), fibroblast growth factor receptor-1 (FGFR-1), FGFR-3, bcl-2, p21, parathyroid hormone-related peptide (PTHrP), and parathyroid hormone-related peptide receptor (PTHR1). Three observers evaluated haematoxylin and eosin (H&E)-stained and immunostained slides independently. Semi-quantitative estimation of the matrix, the type of matrix, and immunostaining was performed. Cellular and matrix-rich areas were evaluated separately. Diverse amounts and types of matrix were present in different tumours, as well as within individual tumours. Signalling molecules were expressed in 50-100% of the cases. Higher levels of expression were found in cellular areas than in matrix-rich areas, especially for PTHR1, bcl-2, and FGFR-3. CB is an unusual entity affecting specific sites, showing that both IHh/PTHrP and FGF signalling are active. Higher expression was found in cellular than in matrix-rich areas, as in the proliferating/pre-hypertrophic growth plate zone in comparison with the hypertrophic/calcifying zone. Previous studies have shown the same molecules to be expressed with a similar pattern in chondrosarcomas. The sum of the evaluated features indicates that CB is a neoplasm originating from a mesenchymal cell committed towards chondrogenesis via active growth plate signalling pathways.

Adolescent↗
PubMed2004

The G972R variant of the insulin receptor substrate-1 (IRS-1) gene is associated with insulin resistance in "uncomplicated" obese subjects evaluated by hyperinsulinemic-euglycemic clamp.

Several association studies have indicated the insulin receptor substrate-1 (IRS-1) gene G972R variant as a genetic risk factor for insulin resistance, particularly in presence of obesity. A few studies have also suggested a possible effect of the G972R variant on insulin secretion. The aim of this study was to evaluate the role of the IRS-1 gene G972R variant in 61 subjects with "uncomplicated" obesity [i.e. without diabetes, hypertension, dyslipidemia, coronary artery disease (CAD)], studied by hyperinsulinemic-euglycemic clamp. The presence of the G972R variant, detected in real-time with LightCycler hybridisation probes, was related to the indexes of insulin sensitivity. Furthermore, the possible role of this variant on insulin secretion was studied by means of insulin release indexes derived from oral tolerance test (OGTT). Twenty-four point five percent (24.5%) (no.=15) of the obese subjects proved to be carriers of the G972R variant. M index (p<0.05), non-oxidative glucose (p<0.01), insulin clearance (p<0.03) and insulin sensitivity index (ISI) (p<0.005) were all significantly reduced in G972R carriers compared to non-carriers, indicating a significant reduction in insulin sensitivity in carriers of the variant. A logistic regression analysis confirmed the independent association between the G972R variant and reduced insulin sensitivity (p<0.03). The interaction between obesity and the G972R variant was also independently associated with a reduced insulin sensitivity (p<0.005), suggesting that obesity and G972R variant were more than additive in predicting insulin resistance. The analysis of insulin release indexes did not show any significant differences. Our results demonstrate the association of the G972R variant of the IRS-1 gene with reduced insulin sensitivity in obese subjects, and indicate a possible interaction between the IRS-1 variant and obesity in worsening of insulin sensitivity.

Adult↗
PubMed2001

The G-308A variant of the Tumor Necrosis Factor-alpha (TNF-alpha) gene is not associated with obesity, insulin resistance and body fat distribution.

BACKGROUND: Tumor Necrosis Factor-alpha (TNF-alpha) has been implicated in the pathogenesis of insulin resistance and obesity. The increased expression of TNF-alpha in adipose tissue has been shown to induce insulin resistance, and a polymorphism at position -308 in the promoter region ofTNF-alpha has been shown to increase transcription of the gene in adipocytes. Aim of this study is to investigate the role of the G-308A TNFalpha variant in obesity and to study the possible influence of this mutation on body fat distribution and on measures of obesity (including Fat Free Mass, Fat Mass, basal metabolic rate), insulin resistance (measured as HOMAIR), and lipid abnormalities. The G-308A TNFalpha polymorphism has been studied in 115 patients with obesity (mean BMI 33.9 +/- 0.5) and in 79 normal lean subjects (mean BMI 24.3 +/- 0.3). METHODS: The G-308A variant, detected by PCR amplification and Nco-1 digestion, determines the loss of a restriction site resulting in a single band of 107 bp [the (A) allele]. RESULTS: The (A) allele frequencies of the G-308A TNFalpha polymorphism were 13.1% in the obese group and 14.6% in the lean subjects, with no significant difference between the two groups. Furthermore, no association was found with BMI classes, body fat distribution, HOMAIR, and metabolic abnormalities. CONCLUSIONS: Our study did not detect any significant association of the G-308A TNFalpha polymorphism with obesity or with its clinical and metabolic abnormalities in this population. Our data suggests that, in our population, the G-308A TNFalpha polymorphism is unlikely to play a major role in the pathogenesis of these conditions.

Journal Article↗
PubMed2001

Single-strand conformation polymorphism analysis of the glucose transporter gene GLUT1 in maturity-onset diabetes of the young.

Maturity-onset diabetes of the young (MODY), an autosomal dominant, early-onset form of type-2 diabetes, is caused by mutations in five different genes all leading to defect(s) in the pancreatic beta cell. However, some patients with this form of diabetes do not bear a mutation in any of the known (MODY1-MODY5) loci, a notion prompting the search for new MODY genes. Clinical and genetic data point toward a defect in beta cell function in the majority of patients with MODY, and partners of the glucose-sensing device are reasonable functional candidates. The high-capacity glucose transporter GLUT2 has the ideal kinetic features for performing this task. However, complete GLUT2 deficiency in humans leads to hepato-renal glycogenosis (Fanconi-Bickel syndrome), and heterozygous GLUT2 mutations apparently behave in a recessive manner. Furthermore, in the human beta cell GLUT1 mRNA is predominant when compared to GLUT2 and glucose influx appears to be largely mediated by this low-Km transporter. Thus, we looked for the presence of sequence variants by polymerase chain reaction and single-strand conformation polymorphism (PCR-SSCP) within the GLUT1 gene in 90 Italian pedigrees negative at the search for mutations in glucokinase (MODY2) and hepatocyte nuclear factor-1alpha (MODY3), the two genes responsible for about 60% of MODY cases in Italian children. We found three already described silent mutations and a new single base deletion in position -173 of the 5' regulatory region. The -173de1A variant, which was detected in the heterozygous or homozygous state in 30.8% of MODY patients examined and is located in a Nuclear Factor Y binding sequence, is not associated with hyperglycemia in affected relatives of MODY probands. In conclusion, it appears from these results that the glucose transporter gene GLUT1 is unlikely to play a major role in the etiology of MODY diabetes.

Adolescent↗
PubMed2001

The G972R variant of the insulin receptor substrate-1 (IRS-1) gene, body fat distribution and insulin-resistance.

AIMS/HYPOTHESIS: Insulin resistance is recognised as the core factor in the pathogenesis of Type II (non-insulin-dependent) diabetes mellitus, hypertension and atherosclerosis. Several studies indicate the possible role of mutations of the insulin receptor substrate-1 (IRS-1) gene in the pathogenesis of insulin-resistance and suggest a possible interaction between the IRS-1 gene and obesity, either by an effect on the development of obesity or by causing or aggravating the obesity-associated insulin resistance. Therefore, the prevalence of the G972R mutation of the IRS-1 gene was compared in 157 non-diabetic obese subjects (BMI > 30 m/kg2) and in 157 lean subjects (BMI < 28 m/kg2). By investigating the relation between this IRS-1 mutation, measures of obesity and metabolic parameters, we explored the possible influence of this mutation on body fat distribution and insulin resistance. METHODS: The G972R mutation was detected by PCR amplification and BstN-1 restriction enzyme digestion. Data were analysed by univariate and multivariate analysis. RESULTS: The G972R allele was significantly more frequent in obese subjects than in lean subjects (p < 0.002); however, no difference was found between centrally and peripherally obese subjects. Obese G972R carriers had significantly higher BMI (p < 0.001), fasting insulin (p < 0.001), triglycerides (p < 0.03) and HOMAIR (p < 0.001) than obese non-carriers. No differences were observed between G972R carriers and non-carriers among control subjects. Multivariate analysis confirmed that the IRS-1 G972R mutation was significantly and independently associated with reduced insulin sensitivity (p < 0.009) in the obese group. CONCLUSION/INTERPRETATION: The G972R mutation of the IRS-1 gene associates with obesity, but not with fat distribution, in this Italian cohort, and within the obese subjects this IRS-1 variant strongly associates with metabolic parameters suggesting greater insulin-resistance. These findings indicate a possible interaction between the IRS-1 variant and obesity in worsening insulin sensitivity.

Adipose Tissue↗
PubMed2000

Pyomyositis in a 5-year-old child.

We present a case of pyomyositis in an otherwise healthy 5-year-old child that underscores the potential for serious, life-threatening complications. Pyomyositis of the gluteal, psoas, and iliacus muscles was associated with osteomyelitis, septic arthritis, a large inferior vena cava thrombus, septic pulmonary emboli, and eventual pneumonia. Primary pyomyositis is a purulent infection of striated muscle thought to be caused by seeding from a transient bacteremia. The focal infection typically forms an abscess that generally responds to intravenous antibiotics and occasionally requires adjunctive computed tomography-guided aspiration and drainage. This localized infectious process rarely produces further sequelae unless treatment is delayed. Pyomyositis is rare in healthy individuals and requires a high clinical suspicion in patients who present with fever, leukocytosis, and localized pain.

Abscess↗
PubMed2000

Ia presynaptic inhibition after muscle twitch in the arm.

Contraction of upper limb muscles in healthy subjects was used to investigate presynaptic inhibition at spinal level. The H reflex recorded in the forearm flexor muscles in response to median nerve stimulation was depressed in amplitude from 400 ms to 1 s after a muscle twitch induced by transcranial stimulation, root stimulation, direct biceps stimulation, and triceps tendon tap. Stimulation of the cutaneous branch of musculocutaneous nerve, ipsilateral triceps and contralateral biceps, and biceps tendon tap did not alter H-reflex size. Forearm flexor H-reflex amplitude is therefore related to changes in proprioceptive inflow secondary to the biceps muscle twitch. Root and direct muscle stimulation both failed to reduce the size of the motor evoked potential (MEP) after transcranial magnetic stimulation, suggesting that the inhibition acts at presynaptic level. Attenuation of H-reflex amplitude was related to the size of the muscle twitch and was less pronounced during an isometric twitch than during free joint movement. Our results suggest that the biceps muscle twitch produces long-lasting inhibition of the Ia afferents from forearm flexor muscles. This is an important and a simple mechanism for suppressing proprioceptive input during movement.

Adult↗
PubMed2000

Changes in the cortical silent period after repetitive magnetic stimulation of cortical motor areas.

The physiological mechanisms underlying the lengthening of the silent period (SP) evoked in active upper limb muscles by repetitive transcranial magnetic stimulation (rTMS) of the motor areas were studied in normal subjects. rTMS was delivered at frequencies of 1 Hz, 2 Hz, 3 Hz, 5 Hz, 10 Hz and 15 Hz and at an intensity just above the motor threshold (Mth). Trains delivered at 2 Hz, 3 Hz, 5 Hz, 10 Hz and 15 Hz significantly prolonged the cortical SP, whereas stimuli at 1 Hz did not. The first few stimuli in the train already prolonged the duration of the cortical SP: the other stimuli did not prolong it further. Motor evoked potentials remained unchanged in amplitude regardless of the frequencies and number of stimuli in the train. The effect of intensity of stimulation was studied by delivering trains at suprathreshold intensity (110% and 140% of Mth) and 3-Hz frequency and with trains at subthreshold intensity and 5-Hz and 10-Hz frequencies. SPs had a longer duration at 140% than at 110% Mth intensity. SPs elicited by 3-Hz trains at 140% and 110% Mth intensity lengthened to a similar extent over the course of the train. rTMS delivered at an intensity below Mth did not evoke cortical SPs over the course of the trains. Repetitive stimulation of the cortical forearm motor areas prolonged the duration of the cortical SP in forearm flexor muscles but failed to evoke SPs in the biceps muscles. The maximal single stimulus intensity and less intense stimuli delivered in short trains evoked SPs of similar duration. We propose that rTMS delivered in trains at frequencies higher than 1 Hz and at suprathreshold intensity prolongs the cortical SP mainly through temporal summation of inhibitory interneurones.

Adult↗
PubMed1999

Effects of repetitive cortical stimulation on the silent period evoked by magnetic stimulation.

The effects of repetitive transcranial stimulation (rTMS) on brain activity remain unknown. In healthy subjects, we studied the effects of rTMS on the duration of the cortical silent period (SP). Repetitive stimuli were delivered with a Cadwell High Speed Magnetic Stimulator and a figure-of-eight coil placed over the hand motor area. rTMS was delivered in trains of 11 or 20 stimuli at frequencies of 3 and 5 Hz and at stimulation intensities of 110 and 120% of motor threshold. The SP was recorded from the forearm muscles during a voluntary contraction (20% of maximum effort). rTMS delivered at a frequency of 3 and 5 Hz and intensities of 110 and 120% motor threshold prolonged the duration of the SP, without modifying either the size or the latency of the muscle-evoked potentials (MEP). A conditioning train of 11 stimuli at 3 Hz had no effect on the duration of the SP evoked by a single magnetic shock delivered 600 ms after the train. These findings show that rTMS increases the duration of the cortical SP, but does so only during the train of stimuli. rTMS probably changes the duration of the SP by facilitating cortical inhibitory interneurons.

Adult↗
PubMed1999

[Correlation between clinical-instrumental pattern in venous pathology (capillaroscopic classification of the medial peri-malleolar area)].

BACKGROUND: The high incidence of chronic venous insufficiency makes it quite an ordinary topic in the outpatients departments of vascular units. Furthermore, due to the discrepancy between symptoms and Doppler c.w reports, it is necessary to face this problem with the help of very sensitive instrumental methods. Therefore, the main aim of this article is to find out which method, among those used in the outpatients department of phlebology, is sensitive enough to establish a relationship between clinical and instrumental patterns in venous diseases. METHODS: Fifty-one subjects were studied: 44 affected by venous disease and 7 healthy subjects. All patients underwent clinical examination followed by classification by Widmer criteria, Doppler c.w., infrared photoplethysmography and capillaroscopy of the medial malleolus. RESULTS AND CONCLUSIONS: Capillaroscopy demonstrated to have the highest sensitivity, allowing to find out pathological alterations in subjects complaining of symptoms and with normal Doppler c.w. findings. Furthermore, the findings of venular networks (pathological) in the malleoli of healthy subjects, made it necessary to modify the current capillaroscopic classification (based upon three types of pictures: normal, reticular and halo formations), into a new extended version based on five steps, with three types of reticular sub-classes, in which the different gauge of the venules is satisfactorily related to the symptoms referred by the patients.

Adolescent↗
PubMed1999

[The determination of the thermal threshold in subjects with Raynaud's disease. A preliminary report of 2 clinical cases].

BACKGROUND: The onset of Raynaud's phenomenon is mainly provoked by cold stimuli which, in patients affected by Raynaud's disease, are milder than those able to provoke the same phenomenon in healthy subjects. Therefore, it is reasonable to theorize the existence of a "thermal threshold", below which it is more likely for a Raynaud's phenomenon to be provoked. The aim of this investigation is to determine whether a thermal threshold in Raynaud's disease exists and if it can be used as a practical tool for preventing the complications of Raynaud's disease (digital gangrene and ulcers), whose onset is strictly related to the frequency of the phenomena. METHODS: Two patients affected, respectively, by slight Raynaud's phenomenon secondary to peripheral neuropathy (Case 1), by severe Raynaud's phenomenon associated with mixed connective tissue disease (Case 2), were asked to write a note about the phenomena and the days of their onset, within a period of three months. Afterwards, all data were related to the daily ground maximum temperature occurred in the period of study. RESULTS AND CONCLUSIONS: These preliminary results show an interesting correlation between this new parameter and the clinical data, the thermal threshold being higher in more severe cases. It was equal to 22 degrees C in the patient affected by slight phenomenon (Case 1), and equal to 27 degrees C in the severe phenomenon (Case 2). This method for evaluating the thermal threshold in these two cases of Raynaud's disease (the greater the figure, the more severe the case) allowed both the clinical assessment of the pathology and the prevention of secondary complications.

Adult↗