Biomedical subjects
Publications and source records attributed to S Angeli.
The authors evaluated the prevalence of right-to-left shunt in 40 subjects with cluster headache (CH) vs 40 subjects without primary headaches or cerebrovascular disease. The diagnosis of shunt was made by means of transcranial Doppler with contrast medium. A shunt was found in 17 CH patients (42.5%) and in 7 controls (17.5%) (p = 0.029; OR = 3.48; 95% CI = 1.13 to 10.69).
Usher syndrome type II is an autosomal recessive disorder characterized by moderate to severe hearing impairment and progressive visual loss due to retinitis pigmentosa (RP). We carried out a mutation screening of the USH2A gene in 88 probands with Usher syndrome type II to determine the frequency of USH2A mutations as a cause for USH2. Six mutations, including 2299delG, 921-922insCAGC, R334W, N346H, R626X, and N357T were identified, with 2299delG mutation being the most frequent (16.5% of alleles), accounting for 77.5% of the pathologic alleles. Thirty-five percent (31/88) of the probands had a USH2A mutation. Nine of them carried two pathogenic mutations: six cases were homozygotes and three were compound heterozygotes. Twenty-two probands (25%) were found to carry only single USH2A mutations. One new missense mutation (N357T) occuring within the laminin N-terminal (type VI) domain of usherin was identified. Eight polymorphisms were found, five of which are novel. Our data support the view that the 2299delG is the most common mutation in USH2A.
OBJECTIVES/HYPOTHESIS: Octreotide is a somatostatin analogue that, when coupled to a radioisotope, produces a scintigraphic image of neuroendocrine tumors (NET) expressing somatostatin type 2 receptors (SSR 2). Octreotide scintigraphy (OS) may be useful in confirming the preoperative diagnosis of certain head and neck NET. Paragangliomas (PG), like many NET, have been found to have a high density of SSR 2 on the cell surfaces. Other NET of the head and neck include merkel cell carcinomas (MCC), medullary thyroid carcinomas (MTC), and esthesioneuroblastomas. STUDY DESIGN: A retrospective study that compared the results of OS with the histopathologic diagnosis in 74 patients with head and neck NET. RESULTS: Of the 60 patients undergoing evaluation for suspected paraganglioma, OS was correctly positive in 36 of the 37 patients with PG. OS was correctly negative in 19 of the 23 patients that did not exhibit PG. For PG, this yielded a sensitivity of 97% and a specificity of 82%. There were 14 patients in the nonparaganglioma group. OS detected or diagnosed all metastases in three patients with MTC, locoregional recurrences in two patients with esthesioneuroblastoma, an extrapituitary adenoma in one patient, and metastasis in two patients with MCC. It failed to detect a paraspinal metastasis in the third patient with MCC. CONCLUSION: On the basis of this series of patients, OS appears to be a reliable test to detect PG and may be helpful in detecting primary and metastatic disease for NET.
Two different classes of chemosensory proteins (CSPs) in Locusta migratoria have been identified on the basis of the molecular cloning of a series of different cDNAs from the antennae of this insect. Several CSP isoforms have been purified and biochemically characterized from antennal and wing extracts, some of them corresponding to expression products predicted for the identified cDNAs. In wings, the nature of the main endogenous ligand binding to these proteins was determined as oleoamide by a gas chromatography-mass spectrometric approach. One of these isoforms has been expressed in a bacterial system with high yield and used in a fluorescent binding assay. Competitive binding experiments have indicated the presence of long-chain compounds among the best ligands.
Right-to-left shunt due to patent foramen ovale is a well-established risk factor for ischemic stroke, especially in young subjects and in patients with cryptogenic stroke. We report a detailed method for the diagnosis of a right-to-left shunt by means of transcranial Doppler as established at a recent consensus conference, and review the literature on the indications for the test.
Chemosensory proteins (CSPs) are a class of small, soluble proteins present at high concentrations in chemosensory organs of different insect species. Several pieces of evidence suggest their involvement in carrying chemical messages from the environment to chemosensory receptors. However, a structural description of the mechanism of delivery has not been reported. In order to provide the first detailed conformational characterization of these molecules, we cloned a specific isoform (CSP-sg4) from Schistocerca gregaria and expressed it in Escherichia coli. The product was obtained with yields of more than 20 mg per L of culture, all in its soluble form. The recombinant protein was identical to the native one with respect to pairing of the disulfide bridges, aggregative state and secondary structure elements. Structural investigations revealed a significantly stable polypeptide with respect to variations in temperature and acidity. CD analysis, preliminary NMR data and secondary structure prediction pointed to a correctly folded structure where helical regions and loops are alternated in a similar fashion as that observed for other classes of odorant- and pheromone-binding proteins presenting no sequence similarity to CSPs.
BACKGROUND AND PURPOSE: Cerebral autosomal dominant angiopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an autosomal dominant hereditary disease whose clinical expression is a stepwise subcortical vascular dementia. Initial presentation of the disease involves transient or stabilized focal neurological deficits, migraine and mood changes. Recently, a high prevalence of right-to-left shunt (RLS) due to patent foramen ovale has been reported in subjects with migraine. The aim of our study was to determine the prevalence of RLS in CADASIL with and without migraine. METHODS: We performed transcranial Doppler with gaseous contrast in 5 members of an Italian family with CADASIL, diagnosed by means of genetic and skin biopsy criteria. We then compared the prevalence of RLS in 40 consecutive subjects with juvenile stroke, 80 asymptomatic subjects affected by migraine with aura and 50 normal controls. RESULTS: A very high prevalence of RLS was found in CADASIL patients (4/5, 80%), as opposed to young subjects with ischemic stroke (15/40, 37%), asymptomatic subjects with migraine (32/80, 40%) and normal controls (8/50, 16%). All the subjects with CADASIL and migraine (4/4) showed RLS. The difference between CADASIL patients and controls was highly significant (p = 0.006). CONCLUSIONS: We suggest an association between CADASIL and RLS, possibly due to the abnormal development of the endocardial cushion influenced by Notch 3 mutation. Our hypothesis needs to be tested in larger samples.
Soluble low molecular weight acidic proteins are suspected to transport stimulus molecules to the sensory neurons within insect sensilla. From the antennae of Bombyx mori, we have purified and sequenced a protein (BmorCSP1) bearing sequence similarity to a class of soluble chemosensory proteins recently discovered in several orders of insects. Based on its N-terminal sequence, the cDNA encoding this protein has been amplified and cloned. Differential screening of a B. mori antennal cDNA library led to the identification of a second gene encoding a related protein (BmorCSP2), sharing 35-40% identity to BmorCSP1 and chemosensory proteins from other species. The predicted secondary structures of moth's, chemosensory proteins comprise alpha-helical foldings at conserved positions and a reduced hydrophobicity with respect to this novel family of chemosensory proteins.
Three related nucleotide sequences, encoding mature proteins of 108-113 amino acids, have been obtained from antennal cDNA of the Phasmid Eurycantha calcarata. Among these, one is also expressed in the tarsi as demonstrated by N-terminal sequence and mass spectrometric analyses of protein samples isolated from both organs. PCR experiments performed with specific primers, showed that this species is also expressed in the mouth organs and in the cuticle, while the other two are antennal specific. All three isoforms are similar to Drosophila OS-D and other proteins reported in several insect orders, but one of them is significantly different from the other two. The best conserved elements are the N-terminal region and the four cysteine residues. Accurate ESMS measurements indicated that all cysteines are involved in two disulphide bonds and ruled out the occurrence of additional post-translational modifications. Polyclonal antibodies, raised against the purified protein, did not react with proteins of the same class expressed in another Phasmid species, Carausius morosus, and in the orthopteran Schistocerca gregaria, nor did antibodies against these proteins recognise those of E. calcarata.
The frequency of childhood deafness is estimated at 1:1,000 and at least half of these cases are genetic. Recently, mutations in the GJB2 gene have been found in a great number of familial and sporadic cases of congenital deafness in Caucasians. The most common mutation (70%) is the frameshift mutation of a single guanine in position 35 (35delG). More than 20 mutations in the GJB2 gene are associated with DFNB1, a prevalent type of autosomal recessive non-syndromic neurosensory deafness. Last year we initiated a systematic screening programme to evaluate the causes of deafness in the population of prelingually deaf children who are referred to our cochlear implant programme. All of the deaf children and their parents undergo a comprehensive medical review, directed to identify causes of acquired deafness and manifestations of syndromic hearing impairment. DNA is extracted from the blood of all of the children. The technique AS-PCR (allele-specific polymerase chain reaction) is used for the identification of the mutation 35delG. Screening for other GJB2 gene mutations is carried out by single-strand conformation polymorphisms (SSCP). Our results on the identification of DFNB1 will be presented, as well as a discussion on the implications of an aetiological diagnosis in cochlear implantation.
Pheromone-binding protein (PBP) and general odorant-binding proteins (GOBPs) were purified from the antennae of Bombyx mori and structurally characterised. The amino acid sequence of GOBP-2 has been corrected. The disulphide arrangements of PBP and GOBP-2 have been determined by a combined mass spectrometric/Edman degradation approach. The same cysteine pairings, Cys19-Cys54, Cys50-Cys108, and Cys97-Cys117, were found in both proteins, suggesting that such patterns occur commonly throughout this family of molecules. This arrangement of disulphide bonds indicates that the three-dimensional structure of insect OBPs is defined by three loops, rich in helical content, which can vary in size and charge distribution from one protein to another.
Transcranial Doppler detection of microembolic signals has been described in several clinical conditions such as carotid stenosis, prosthetic heart valves, acute stroke, and carotid surgery. The importance of these events for clinical decision-making is still a matter of debate. The authors review the literature and report their personal experience on the clinical significance of microemboli detection.
Soluble low-molecular-mass protein isoforms were purified from chemosensory organs (antennae, tarsi and labrum) of the desert locust Schistocerca gregaria. Five genes encoding proteins of this group were amplified by PCR from cDNAs of tarsi and sequenced. Their expression products are polypeptide chains of 109 amino acids showing 40-50% sequence identity with putative olfactory proteins from Drosophila melanogaster and Cactoblastis cactorum. Direct structural investigation on isoforms purified from chemosensory organs revealed the presence in the expression products of two of the genes cloned. Two additional protein isoforms were detected and their molecular structure exhaustively characterized. MS analysis of all isoforms demonstrated that the four cysteine residues conserved in the polypeptide chain were involved in disulfide bridges (Cys29-Cys38 and Cys57-Cys60) and indicated the absence of any additional post-translational modifications. Immunocytochemistry experiments, performed with rabbit antiserum raised against the protein isoform mixture, showed selective labelling of the outer lymph in contact sensilla of tarsi, maxillary palps and antennae. Other types of sensilla were not labelled, nor were the cuticle and dendrites of the sensory cells. No binding of radioactively labelled glucose or bicarbonate was detected, in disagreement with the hypothesis that this class of proteins is involved in the CO2-sensing cascade. Our experimental data suggest that the proteins described here could be involved in contact chemoreception in Orthoptera.
Stapes surgery for correction of conductive hearing loss in adults with otosclerosis is a well-established procedure. Its effectiveness in children, however, has received less scrutiny in the literature. Previous studies from our and other institutions demonstrated similar results in children and adults. Between 1980 and 1994 stapedectomies were done on 95 ears of 81 patients younger than 18 years (83 primary and 12 revisions). Data regarding age of onset, family history, associated anomalies, surgical findings, technique, hearing results, and complications were reviewed. Two groups were identified: congenital stapedial fixation and juvenile otosclerosis. Patients with congenital stapedial fixation had an earlier onset of hearing loss (3 vs 10 years, P < 0.001), a greater incidence of abnormalities of the malleus and incus (25% vs 3%, P < 0.001), and a slightly greater preoperative air-bone gap (35.2 +/- 12.9 vs 27.8 +/- 8.9, P = 0.002). Patients with otosclerosis had a greater frequency of a positive family history of deafness (53% vs 10%, P < 0.001). Overall, 79% of primary cases and 89% of revision cases had an improvement in hearing, with mean postoperative air-bone gaps of 15 dB and 22 dB, respectively. The gap did not widen significantly during the entire length of follow-up (mean 72 months). In primary cases, 59.1% obtained a postoperative air-bone gap of 10 dB or less. Eighty-two percent of children operated on for otosclerosis obtained excellent results (postoperative air-bone gap < or = 10 dB), compared with only 44% of children with congenital stapedial ankylosis (P = 0.02). In revision surgery, 29% of children obtained excellent results. Poorer results in both cases of congenital stapedial fixation and revision stapedectomy appear to be related to the greater incidence of associated anomalies of the malleus and incus. Indications, technique, complications, and considerations pertinent to childhood stapedectomy are discussed.
Microembolic signals (MES) have been described in patients with different types of prosthetic valves. The aim of our study was to compare prevalence of MES in patients with mono-leaflet and bi-leaflet valves, and to correlate them with different clinical and echocardiographic parameters. We evaluated 42 patients, 15 with mono-leaflet and 27 with bi-leaflet valves, with 30-minute bilateral simultaneous transcranial Doppler monitoring for the identification of MES. All patients performed blood testing for international normalized ratio (INR), color-coded duplex of supra-aortic vessels, and echocardiography. Eighteen patients (43%) showed MES; 61% of MES were detected bilaterally, 17% only on the left and 22% only on the right middle cerebral artery (MCA), with no interhemispheric difference. MES did not correlate with patient's age, echocardiographic parameters, INR, presence of atrial fibrillation, or site of valve replacement. One (7%) of the 15 patients with mono-leaflet valves had MES, as opposed to 17 (63%) of the 27 with bileaflet valves (p=0.0003). Patients with bileaflet valves and MES had valves of older implantation and, only for aortic valves, larger valve size.
AIMS: Although fine needle biopsy (FNB) is a well established diagnostic technique there continues to be controversy concerning its use in the pre-operative assessment of intraparotid masses. The purpose of this study was to evaluate the diagnostic accuracy, specificity and sensitivity of FNB in parotid tumours and consequently to asses its clinical value. METHODS: Over a 6-year period, 129 consecutive patients with parotid masses underwent pre-operative FNB evaluation and in 121 of these cases the cytological diagnosis was confirmed. RESULTS: Out of the 86 cases cytologically diagnosed as benign, two false negative results were obtained by FNB, whereas out of the 38 cytological diagnoses of malignant tumours one case was found histologically to be Warthin's tumour. In the FNB results of the two cases suspicious for malignancy, one was confirmed histologically as malignant. Three cases of FNB with inadequate material were found to be benign lesions. In this trail, the diagnostic accuracy of FNB was 96.7%, the specificity, 97.6% and the sensitivity, 95%. CONCLUSIONS: Our results show that FNB is a valuable examination technique in the pre-operative evaluation of parotid masses.
BACKGROUND AND PURPOSE: The occurrence of microembolic signals (MES) in patients with transient ischemic attack (TIA) or stroke has already been described, but the diagnostic and prognostic value of this finding is still debated. METHODS: We evaluated 90 consecutive patients admitted for their first hemispheric TIA or ischemic stroke within 72 hours of onset. All of them underwent 30-minute bilateral transcranial Doppler monitoring of middle cerebral arteries, within 72 hours of onset. The monitoring was repeated after an additional 24 hours and after 7 days. We then classified the episodes in the following etiologic categories: cardioembolic, atherothrombotic, small-vessel disease, mixed cases, unknown origin, and other causes. RESULTS: We included 75 patients, with a mean interval of registration of 32.04 +/- 19.39 hours. There were 9 patients with MES (12%). All MES were recorded only on the symptomatic middle cerebral artery, and the majority were recorded during the first or the second registration. No statistically significant difference was found in risk factors and hematologic parameters. Five patients (56%) had atherothrombotic episodes, 3 patients (33%) had cardioembolic episodes, and 1 patient (11%) had a protein S deficit. No patient with MES had small-vessel disease (P = .01). CONCLUSIONS: MES are an infrequent finding in patients with TIA or ischemic stroke within 72 hours of onset, but they can be recorded more easily with serial registration. In our patients, MES were found only on the symptomatic middle cerebral artery and were present in atherothrombotic and cardioembolic episodes but not in small-vessel disease.
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