PubMed Health⌕ Search

Biomedical subjects

L Verga

Publications and source records attributed to L Verga.

At least 19 recordsLinked to original sources
PubMed1999

Infantile neuroaxonal dystrophy: clinical spectrum and diagnostic criteria.

OBJECTIVE: To present clinical, neurophysiologic, and neuroradiologic findings in 13 patients with infantile neuroaxonal dystrophy (INAD), focusing on aspects that assist early diagnosis. BACKGROUND: Clinicopathologic diagnostic criteria for INAD were delineated by Aicardi and Castelein in 1979, but atypical cases are reported frequently and little is known of the diagnostic utility of MRI. METHODS: The authors reviewed the clinical, neurophysiologic, and MRI findings of 13 patients who met the diagnostic criteria for INAD. RESULTS: Symptoms onset was between 6 months and 2 years of age. In nine patients the clinical course was typical, with rapid motor and mental deterioration; in four patients progression was slower and the clinical picture was different. Electromyographic (EMG) signs of chronic denervation, fast rhythms on EEG and abnormal visual evoked potentials were observed in all patients during the disease course. Cerebellar atrophy with signal hyperintensity in the cerebellar cortex on T2-weighted images were the most characteristic MRI findings; hypointensity in the pallida and substantia nigra was also observed in two patients. alpha-N-acetyl-galactosaminidase activity on leukocytes was normal in the 10 patients tested. CONCLUSIONS: EMG and MRI abnormalities are the earliest and most suggestive signs of INAD, which has a clinical and radiologic spectrum that is broader than reported previously.

Adolescent↗
PubMed1999

Infantile neuroaxonal dystrophy: neuroradiological studies in 11 patients.

We report the imaging findings in 11 patients with infantile neuroaxonal dystrophy. Ten patients underwent 15 MRI examinations; one patient had only CT. Of the ten patients who underwent MRI, eight had cerebellar atrophy and mildly increased signal from the cerebellar cortex on T2-weighted images. With T2 weighting there was slightly increased signal from the dentate nuclei in two patients and from the posterior periventricular white matter in three. We saw four patients with a thin optic chiasm. The only two brothers in the series had markedly low signal from the globus pallidus and substantia nigra on 1.5 T T2-weighted images, as seen in Hallervorden-Spatz disease (HSD). Abnormalities of the globus pallidus may be related to a protracted course of the disease. However, an overlap with HSD should be considered.

Brain↗
PubMed1999

The new apolipoprotein A-I variant leu(174) --> Ser causes hereditary cardiac amyloidosis, and the amyloid fibrils are constituted by the 93-residue N-terminal polypeptide.

We identified a novel missense mutation in the apolipoprotein A-I gene, T2069C Leu(174) --> Ser, in a patient affected by familial systemic nonneuropathic amyloidosis. The amyloid deposits mostly affected the heart of the proband, who underwent transplantation for end-stage congestive heart failure. Amyloid fibrils of myocardial and periumbilical fat samples immunoreacted exclusively with anti-ApoA-I antibodies. Amyloid fibrils extracted from the heart were constituted, according to amino acid sequencing and mass spectrometry analysis, by an amino-terminal polypeptide ending at Val(93) of apolipoprotein A-I (apoA-I); no other significant fragments were detected. The mutation segregates with the disease; it was demonstrated in the proband and in an affected uncle and excluded in three healthy siblings. The plasma levels of high-density lipoprotein and apoA-I were significantly lower in the patient than in unaffected individuals. This represents the first case of familial apoA-I amyloidosis in which the mutation is outside the polypeptide fragment deposited as fibrils. Visualization of the mutation in the three-dimensional structure of lipid-free apoA-I, composed of four identical polypeptide chains, indicates that position 174 of one chain is located near position 93 of an adjacent chain and suggests that the amino acid replacement in position 174 is permissive for a proteolytic split at the C-terminal of Val(93).

Amino Acid Substitution↗
PubMed1999

Selection of patients for carotid endarterectomy: the role of ultrasound.

Stroke is the third leading cause of death in the western world and the major cause of disability among the middle aged and elderly populations. Carotid artery stenosis is the single most important risk factor for stroke. The North American Symptomatic Carotid Endarterectomy Trial and the European Carotid Surgery Trial have demonstrated that the risk of stroke is reduced by surgery in patients with high grade stenosis. Carotid plaque morphology also plays an important role; plaques which are ulcerated and echolucent are associated with a higher risk of stroke. Arteriography has long been regarded as the gold standard diagnostic tool for evaluation of carotid artery disease, but it is an invasive and costly technique which carries the risk of potentially serious complications. Doppler ultrasound can provide functional and anatomical information on vessel stenosis and plaque morphology at sub-millimetric resolutions and is an inexpensive and noninvasive tool. Color and spectral Doppler ultrasound are now recognized as the best screening tests for carotid artery stenosis. The evidence for its use as the sole diagnostic imaging modality prior to carotid endarterectomy is examined. The recent availability of ultrasound contrast agents helps to distinguish between pseudo- and true occlusions, improves ultrasound images and should help to reduce operator variability.

Blood Flow Velocity↗
PubMed1999

Lipoblastoma and lipoblastomatosis in children.

Lipoblastoma and lipoblastomatosis are rare mesenchymal benign tumors of embryonal white fat. They are found primarily in children less than 5 years of age. This tumor presents in two forms: a localized well-circumscribed lesion (lipoblastoma), or a multicentric type (lipoblastomatosis). The authors presents three cases, two of them with a buttock lesion, the last with a paravertebral one. It is recommended a complete but conservative excision of the tumor because there is a natural tendency to involution, although in the first year of life a local reexcision for recurrence is sometimes described.

Abdominal Neoplasms↗
PubMed1998

Stem cell factor in mast cells and increased mast cell density in idiopathic and ischemic cardiomyopathy.

BACKGROUND: We compared cardiac mast cell (HHMC) density and the immunological and nonimmunological release of mediators from mast cells isolated from heart tissue of patients with idiopathic dilated (DCM) (n=24) and ischemic cardiomyopathy (ICM) (n = 10) undergoing heart transplantation and from control subjects (n = 10) without cardiovascular disease. METHODS AND RESULTS: HHMC density in DCM (18.4+/-1.6 cells/mm2) and ICM (18.4+/-1.5 cells/mm2) was higher than that in control hearts (5.3+/-0.7 cells/mm2; P<.01). The histamine and tryptase contents of DCM and ICM hearts were higher than those of control hearts. The histamine content of the hearts was correlated with mast cell density (r(s)=.91; P<.001). Protein A/gold staining of heart tissue revealed stem cell factor (SCF), the principal growth, differentiating, and activating factor of human mast cells, in HHMC secretory granules. Histamine release from cardiac mast cells caused by immunological (anti-IgE and rhSCF) and nonimmunological stimuli (Ca2+ ionophore A23187) was higher in patients with DCM and ICM compared with control subjects. Immunological activation of HHMC induced a significantly greater release of tryptase and LTC4 in patients with DCM and ICM compared with control subjects. CONCLUSIONS: Histamine and tryptase content and mast cell density are higher in failing hearts than in control hearts. SCF, present in secretory granules of HHMC, might represent an autocrine factor sustaining mast cell hyperplasia in heart tissue in these patients. The increased local release of fibrogenic factors (eg, histamine, tryptase, and leukotriene C4) might contribute to collagen accumulation in the hearts of patients with cardiomyopathy.

Adult↗
PubMed1998

Restrictive cardiomyopathy, atrioventricular block and mild to subclinical myopathy in patients with desmin-immunoreactive material deposits.

OBJECTIVES: We present clinical data and heart and skeletal muscle biopsy findings from a series of patients with ultrastructural accumulations of granulofilamentous material identified as desmin. BACKGROUND: Desmin cardiomyopathy is a poorly understood disease characterized by abnormal desmin deposits in cardiac and skeletal muscle. METHODS: Clinical evaluation, endomyocardial and skeletal muscle biopsy, light and electron microscopy and immunohistochemistry were used to establish the presence of desmin cardiomyopathy. RESULTS: Six hundred thirty-one patients with primary cardiomyopathy underwent endomyocardial biopsy (EMB). Ultrastructural accumulations of granulofilamentous material were found in 5 of 12 biopsy samples from patients with idiopathic restrictive cardiomyopathy and demonstrated specific immunoreactivity with anti-desmin antibodies by immunoelectron microscopy. Immunohistochemical findings on light microscopy were nonspecific because of a diffuse intracellular distribution of desmin. All five patients had atrioventricular (AV) block and mild or subclinical myopathy. Granulofilamentous material was present in skeletal muscle biopsy samples in all five patients, and unlike the heart biopsy samples, light microscopic immunohistochemical analysis demonstrated characteristic subsarcolemmal desmin deposits. Two patients were first-degree relatives (mother and son); another son with first-degree AV block but without myopathy or cardiomyopathy demonstrated similar light and ultrastructural findings in skeletal muscle. Electrophoretic studies demonstrated two isoforms of desmin--one of normal and another of lower molecular weight--in cardiac and skeletal muscle of the familial cases. CONCLUSIONS: Desmin cardiomyopathy must be considered in the differential diagnosis of restrictive cardiomyopathy, especially in patients with AV block and myopathy. Diagnosis depends on ultrastructural examination of EMB samples or light microscopic immunohistochemical studies of skeletal muscle biopsy samples. Familial desminopathy may manifest as subclinical disease and may be associated with abnormal isoforms of desmin.

Adolescent↗
PubMed1998

Heterotopic pancreatic tissue at umbilicus.

Heterotopic pancreatic tissue at the umbilicus is a very rare anomaly with only 4 cases previously reported in the literature: we describe our experience with 2 additional cases.

Choristoma↗
PubMed1996

Human synovial mast cells. I. Ultrastructural in situ and in vitro immunologic characterization.

OBJECTIVE: To examine the ultrastructure of human synovial mast cells in situ, to identify immunologic and nonimmunologic stimuli that activate these cells in vitro, and to quantify a number of preformed and de novo-synthesized mediators. METHODS: We conducted an ultrastructural study of synovial mast cells in situ and performed immunoelectron microscopy localization of tryptase and chymase. Isolated synovial mast cells were analyzed biochemically, immunologically, and functionally in vitro and compared with cells from human lung, heart, and skin. RESULTS: Ultrastructural study of synovial tissue revealed mast cells with homogeneously dense, scrolled, crystal, and mixed granules, and lipid bodies in the cytoplasm. A small percentage of mast cells showed evidence of degranulation. Immunoelectron microscopy demonstrated the subcellular localization of tryptase and chymase over granules of > 90% of the mast cells, which were of the MCTC subtype. Isolated synovial mast cells released histamine in response to immunologic (anti-IgE and anti-Fc epsilon receptor I [anti-Fc epsilon RI]) and nonimmunologic (substance P, recombinant human stem cell factor, and 48/80) stimuli, but did not respond to recombinant human C5a in vitro. Synovial mast cells differed from those isolated from other human tissues, in a variety of immunologic and biochemical features. There was a linear correlation between the percentage of histamine secretion and tryptase release (r = 0.79, P < 0.001) induced by cross-linking of Fc epsilon RI. Cross-linking of IgE with anti-IgE on synovial mast cells induced de novo synthesis of prostaglandin D2 (mean +/- SEM 87.5 +/- 4.9 ng/10(6) cells) and of leukotriene C4 (57.6 +/- 17.8 ng/10(6) cells). CONCLUSION: Mast cells ultrastructurally characterized in situ in synovial tissue were seen to differ from mast cells previously isolated from other human tissues. This raises the possibility that the local microenviroment influences their phenotype. Isolation of mast cells from human synovia can be useful for studying their role and their mediators in patients with arthritis.

Adult↗
PubMed1996

beta PP and Tau interaction. A possible link between amyloid and neurofibrillary tangles in Alzheimer's disease.

Extracellular deposition of amyloid fibrils and intraneuronal accumulation of paired helical filaments (PHFs) are the neuropathological hallmarks of Alzheimer's disease. The major constituent of amyloid fibrils is a 39- to 43-residue peptide (termed A beta), which is derived from a 695- to 770-amino-acid precursor protein (termed beta PP). The main component of PHFs identified so far is the microtubule-associated protein tau. Yet, there is no direct evidence of interconnection between these two pathological states. We report here that antibodies to an epitope located between residues 713 and 723 of beta PP770 (ie, the transmembrane region of beta PP distal to A beta) consistently labeled PHFs in the brain of Alzheimer patients. Solid phase immunoassay showed that a peptide homologous to residues 713 to 730 of beta PP770 bound tau proteins. This beta PP peptide spontaneously formed fibrils in vitro and, in the presence of tau, generated dense fibrillary assemblies containing both molecules. These data suggest that beta PP or beta PP fragments containing the tau binding site are involved in the pathogenesis of PHFs in Alzheimer's disease.

Alzheimer Disease↗
PubMed1996

[A follow-up study in individuals subjected to ileo-cecal resection in infancy and childhood].

It is stated that the ileocecal valve delays the passage of ileal contents into the cecum and acts as a barrier against reflux and ascension of colonic bacterial flora into the small bowel: its resection may lead to bacterial colonization of the ileum and to abnormalities of intestinal motility, transit and absorption. In this study twenty individuals subjected in pediatric age (1 day to 11 years) to ileocecal resection have been evaluated from 2 to 19 years after surgery. Three patients underwent limited ileocecal resection, in four this was associated with a significant ileal resection, in five with extensive right colon resection and in eight with extensive ileal and right colon resection. Growth, stool habit, hematology and serum biochemistry were examined; all patients also underwent abdominal ultrasonography. In all body weight and height were within normal limits; seven had moderate diarrhea up to 18 months after surgery and two who required extensive intestinal resection (40 and 30 cm of small bowel left) had diarrhea until about 36 months after surgery: now all of them have daily fecal evacuation. Hematological, biochemical, urinary and fecal studies proved normal except in one treated with TPN who presented transaminases slightly increased and in three suffering from mucoviscidosis in whom steatorrhea with moderate alterations of fats and elevation of alkaline phosphatase and transaminases were present. Urinary and gall stones were not seen in anyone. In conclusion from this study it can be postulated that removal of ileocecal valve can be done safely in children.

Anthropometry↗
PubMed1994

A neurotoxic prion protein fragment induces rat astroglial proliferation and hypertrophy.

Prion-related encephalopathies are characterized by the accumulation of an abnormal prion protein isoform (PrPSc) and the deposition of PrP amyloid in the brain. This process is accompanied by neuronal loss and astrogliosis. We recently showed that a synthetic peptide corresponding to residues 106-126 of human PrP is amyloidogenic and causes neuronal death by apoptosis in vitro. In the present study we investigated the effects of 1- and 14-day exposures of rat astroglial cultures to micromolar concentrations of this peptide as well as peptides homologous to other portions of PrP, a peptide corresponding to residues 25-35 of amyloid-beta protein, and a scrambled sequence of PrP 106-126. No significant changes were observed after 1-day exposure of cultures to any peptide. Conversely, 14-day treatment with PrP 106-126 (50 microM) resulted in a 5-fold increase in glial fibrillary acidic protein (GFAP) expression, as evaluated by Northern and Western blot analyses, and a 1.5-fold increment in cell number. Light and electron microscopy immunohistochemistry showed an enlargement in size and density of astroglial processes, and an increase in GFAP-immunoreactive intermediate filaments. These changes were not observed after 14-day treatment of cultures with the other peptides, including PrP 106-126 scrambled. The increase in GFAP expression of astroglial cultures exposed to PrP 106-126 was quantitatively similar to that found in scrapie-infected hamster brains.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1993

Synthetic peptides homologous to prion protein residues 106-147 form amyloid-like fibrils in vitro.

Gerstmann-Sträussler-Scheinker disease (GSS) is a prion-related encephalopathy pathologically characterized by massive deposition of prion protein (PrP) amyloid in the central nervous system. The major component of amyloid fibrils isolated from patients of the Indiana kindred of GSS (GSS-Ik) is an 11-kDa fragment of PrP spanning residues 58 to approximately 150. These patients carry a missense mutation of the PRNP gene, causing a Phe-->Ser substitution at codon 198. We investigated fibrillogenesis in vitro by using synthetic peptides homologous to consecutive segments of GSS-Ik amyloid protein (residues 57-64, 89-106, 106-126, and 127-147) as well as peptides from the PrP region with the GSS-Ik mutation (residues 191-205 and 181-205, both wild type and mutant). Peptide PrP-(106-126) formed straight fibrils similar to those extracted from GSS brains, whereas peptide PrP-(127-147) formed twisted fibrils resembling scrapie-associated fibrils isolated from subjects with transmissible spongiform encephalopathies. Congo red staining and x-ray fibril diffraction showed that both straight and twisted fibrils had tinctorial and conformational properties of native amyloid. Conversely, the other peptides did not form amyloid-like fibrils under similar conditions. These findings suggest that the sequence spanning residues 106-147 of PrP is central to amyloid fibril formation in GSS and related encephalopathies.

Amino Acid Sequence↗
PubMed1993

A68 is a component of paired helical filaments of Gerstmann-Sträussler-Scheinker disease, Indiana kindred.

Gerstmann-Sträussler-Scheinker disease in the Indiana kindred is pathologically characterized by prion protein amyloid deposits and neurofibrillary tangles (NFT) with paired helical filaments (PHF). Using antibodies to various domains of the tau molecule, we investigated the composition of PHF in this family by immunocytochemistry and immunoblot analysis. The results indicate that A68 is a component of NFT in this family as it is in Alzheimer's disease, and suggest that post-translational modifications of tau leading to formation of A68 are not unique to Alzheimer's disease.

Aged↗
PubMed1993

Apoptosis mediated neurotoxicity induced by chronic application of beta amyloid fragment 25-35.

To investigate whether and how amyloid-beta protein (A beta) is involved in the neurodegenerative changes characteristic of Alzheimer's disease (AD), primary hippocampal neurones from foetal rat brain were exposed acutely and chronically to micromolar concentrations of a synthetic peptide homologous to residues 25-35 of A beta (beta 25-35). A single application of this peptide (25-100 microM) was ineffective but when the neuronal cultures were exposed to beta 25-35 (25-100 microM) repeatedly every two days for ten days, cell survival was dramatically reduced. The structural changes and the DNA fragmentation of cells chronically exposed to the peptide suggested that neuronal death occurred by apoptosis. Furthermore, beta 25-35 showed the intrinsic ability to polymerize into amyloid-like fibrils in vitro. These results confirm the potential pathogenic role of A beta in AD, and indicate that amyloid fibrils may induce neuronal death through a specific programmed process.

Amino Acid Sequence↗
PubMed1993

Beta PP participates in PrP-amyloid plaques of Gerstmann-Sträussler-Scheinker disease, Indiana kindred.

Gerstmann-Sträussler-Scheinker disease in the Indiana kindred is pathologically characterized by deposits of PrP-amyloid, neurofibrillary tangles and degenerating neurites. The aim of this study was to investigate seven patients of different ages for beta PP and A beta immunoreactivities associated with PrP-amyloid deposits and degenerating neurites. In one asymptomatic individual with PrP-amyloid deposits, Alz50 and A beta immunoreactivities were absent. In six symptomatic patients, the degenerating neurites surrounding PrP-amyloid deposits were labeled by Alz50 and by antibodies to synaptophysin, ubiquitin and the N- and C-terminal domains of beta PP. In one symptomatic, senile patient, A beta immunoreactivity was present in the extracellular space, often in association with PrP-amyloid deposits. The analysis of the immunohistochemical findings suggested that in the Indiana kindred the intracellular accumulation of beta PP, synaptophysin and ubiquitinated material most probably revealed a reaction of neurites to PrP-amyloid, whereas the extracellular deposition of A beta was likely an age-related phenomenon.

Aged↗