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Biomedical subjects

G Paludetti

Publications and source records attributed to G Paludetti.

At least 73 records · Page 4Linked to original sources

Phenotype of in vitro human otosclerotic cells and its modulation by TGF beta.

A study was carried out to obtain a more detailed picture of the phenotypes of human otosclerotic and normal bone cells and to analyse the response of both populations to treatment with TGF beta 1. Total collagen synthesis was found to be decreased, but fibronectin secretion increased in otosclerotic with respect to normal cells. Although overall glycosaminoglycan (GAG) synthesis was lower in otosclerotic cells, the sulphated GAG to hyaluronic acid (HA) ratio was higher, in particular there was greater expression of chondroitin (CS) and dermatan sulphates (DS). TGF beta 1 induced a more marked increase in collagen and fibronectin release and greater production of sulphated GAGs as DS and heparan sulphate (HS) in the otosclerotic cells. The fact that the phenotype of the otosclerotic cells differed from that of the normal cells and could be modified by TGF beta 1 treatment, suggests that TGF beta 1 is implicated in the pathogenesis of otosclerosis.

Bone and Bones↗

Expression of ras oncogene p21 protein in normal and neoplastic laryngeal tissues: correlation with histopathological features and epidermal growth factor receptors.

Western blotting analysis of the p21 ras oncoprotein was performed in seven normal laryngeal mucosa specimens and 43 primary laryngeal cancers. Varying p21 levels, expressed as optical density (OD), were found in normal mucosa (median 1.94 OD, range 0.90-2.17 OD) and in primary laryngeal tumours (median 1.74 OD, range 0.30-6.37 OD). When p21 expression in laryngeal cancer was compared with the normal counterpart, higher levels were found in neoplastic than in normal laryngeal tissue (median 2.54 OD, range 1.76-6.37 OD, vs median 1.94 OD, range 0.90-2.17 OD) (P = 0.023). Immunohistochemical analysis demonstrated that most of the tumour cells (more than 70%) were immunostained while the stromal component was unreactive. No correlation between p21 expression and tumour location, stage and histopathological grade was observed. The correlation between ras p21 protein expression and epidermal growth factor receptor (EGFR) levels was also investigated. EGFR-positive cases did not show any difference in p21 expression with respect to EGFR-negative cases (median 1.52 OD, range 0.30-6.37 OD, vs median 1.84 OD, range 0.93-3.71 OD). Our findings suggest that overexpression of p21 protein is associated with a malignant phenotype in laryngeal cancer. Further studies should be undertaken to evaluate whether the assessment of p21 protein expression may have clinical significance in laryngeal cancer.

Adult↗

Brain SPET and auditory cortex perfusion. Technical notes and preliminary results.

Auditory cortex stimulation was studied by 99Tcm-hexamethylpropyleneamine oxime (HMPAO) single photon emission tomography (SPET) in 11 patients with normal vestibular and auditory tests, as well as computed tomography. Markedly increased temporal and parietal blood flows were found in left brain cortex, contralateral to the stimulus. The right auditory areas showed moderate hyperactivity. The method might be useful for tonotopic mapping of auditory cortex, using various pure tonal stimuli.

Acoustic Stimulation↗

PTH induces modification of transductive events in otosclerotic bone cell cultures.

We studied the effect of PTH (10-100 nM) on transductive mechanisms (adenylate cyclase activity, Ca2+ metabolism, IP3 levels) in cell cultures derived from normal and otosclerotic human bone fragments. The cultured cells were osteoblast-like but with calcitonin-receptors still present and with PTH receptors coupled with the adenylate cyclase system. The results showed that PTH activated adenylate cyclase and increased the intracellular Ca2+ levels with qualitative and quantitative differences between the two cellular populations. In particular, otosclerotic cells responded less to hormone stimulation, which is in accord with the current hypothesis of a desensitization of the receptor/enzyme complex associated with the pathological status.

Adenylyl Cyclases↗

Cathepsin D in primary squamous laryngeal tumors: correlation with clinico-pathological parameters and receptor status.

Using an immunoradiometric assay, Cathepsin D (Cath D) levels were measured in the cytosol of 23 normal and 39 neoplastic human laryngeal tissues. Scattered Cath D levels (from 2.2 to 17.8 pM/mg protein; median = 7.6) were found in normal mucosa specimens. Cath D concentrations range from 2.0 to 29.3 pM/mg protein (median = 8.5) in laryngeal tumors. When a comparison between Cath D levels in normal and neoplastic tissue specimens from the same patient was done, Cath D levels were significantly higher in laryngeal cancers than in their normal counterparts (P = 0.03). No correlation with clinico-pathological parameters and steroid hormone and epidermal growth factor receptor status was found. Further studies should investigate whether the production of Cath D by laryngeal tumors could have a clinical relevance for this neoplasia.

Adult↗

EGF receptor expression in primary laryngeal cancer: correlation with clinico-pathological features and prognostic significance.

Epidermal-growth-factor-receptor(EGFR) expression was evaluated in 103 primary laryngeal tumors and in 42 normal laryngeal tissue specimens. Significantly higher EGFR levels were found in cancer specimens than in normal mucosa (p = 0.0053). EGFR expression did not correlate with age, tumor localization, T classification, cervical-lymph-node involvement or type of surgery, whereas it was higher in poorly differentiated tumors (G3) than in well/moderately differentiated (G1-G2) tumors (p < 0.05). Follow-up data were available for 74 patients. When EGFR status and the most important clinico-pathological characteristics were submitted to univariate analysis, tumor localization, type of surgery and EGFR status were found to be significantly correlated with disease-free survival. The 24-month disease-free survival rate was 58% for EGFR+ cancer patients and 82% for EGFR- ones. With multivariate analysis, only EGFR status and tumor localization were identified as significant independent prognostic parameters. Data reported here suggest that high EGFR levels may identify a sub-set of laryngeal-cancer patients with a particularly unfavorable prognosis.

Adult↗

Plexiform neurofibroma of the cervical portion of the vagus nerve.

The authors describe a rare case of plexiform neurofibroma of the cervical portion of the vagus nerve, and discuss its aetiopathogenesis, clinical, histological and therapeutic features, emphasizing the difference from other benign tumours of the vagus nerve. The clinical characteristics of the mass, ultrasound tomography, CT scanning and digital subtraction angiography were useful in defining its extension and relationships with the surrounding structures. Surgery is the treatment of choice. After mentioning the most commonly employed surgical approaches, they emphasize the advantages of the lateral-cervical approach which allows a wide exposure of the possible sites of origin of the tumour and its complete removal. Finally they stress the need of an accurate histological and immunohistochemical examination in order to differentiate neurofibromas from neurilemmomas.

Adult↗

Functional study of the eustachian tube with sequential scintigraphy.

The authors investigated the tubal function by means of sequential scintigraphy in 16 patients affected by chronic otitis media and in 3 patients with posttraumatic perforation of the tympanic membrane. Evaluated parameters were: appearance time (AT), radioactivity peak time, rise time in the tympanic cavity, eustachian tube and rhinopharynx, and radioactivity percent values passed in the rhinopharynx. The tubal pressure-equilibrating function was determined by means of the manometer pump section of the impedance meter. A significant relationship between the pressure-equilibrating function and the tubal scintigraphy parameters has been detected. The variability of the AT in the tube and the almost constant time needed by the radioactive tracer to go through the tube and reach the rhinopharynx could indicate that a major role in the tympanic cavity drainage is played by the tympanic ostium and the surrounding mucosa.

Chronic Disease↗

Receptors for epidermal growth factor and steroid hormones in primary laryngeal tumors.

The authors investigated the presence of epidermal growth factor (EGF-R), estrogen (ER), progesterone (PR), and androgen (AR) receptors in 42 laryngeal squamous cell carcinomas and 20 normal laryngeal mucosa specimens. EGF-R were expressed in all tumor specimens analyzed, with significantly higher levels in tumor samples compared with normal mucosa (P less than 0.05). The immunohistochemical study demonstrated the presence of EGF-R in basal and parabasal cells of normal mucosa and in most of the cancer cells. There was no correlation between EGF-R and tumor localization or T classification. On the other hand, the authors did find an interesting correlation between EGF-R levels and grading, EGF-R levels being significantly higher in G3 than in G1-G2 tumors. Moreover, the three patients whose tumors expressed the highest EGF-R levels had disease recur within 8 months. Among tumor specimens, 9.5%, 35.7%, and 9.5% expressed very low but detectable ER, PR, and AR levels, respectively. No statistically significant difference was found between the levels of steroid receptors in the tumor and normal mucosa specimens, and neither was there any correlation of ER, PR, and AR with the pathologic findings. The authors' results suggest that the EGF-R system may play a role in regulating the growth of laryngeal cancer. Additional studies should demonstrate whether, as in other tumor types, EGF-R expression may have prognostic significance in human laryngeal cancer.

Adult↗

Characterization of the cytoskeleton in human normal and otosclerotic osteoblast-like cells.

The localization and distribution of some cytoskeletal protein components were studied by immunostaining methods in normal and ostosclerotic osteoblast-like cells. The protein components investigated were microtubules (beta-tubulin), intermediate filaments (vimentin), microfilaments (actin and myosin) and structural proteins (alpha-actinin and fibronectin). Although the mechanism is not yet clear, the alterations observed in the pathological cells could well play a role in the expression of otosclerosis.

Actinin↗

Effects of steroids on human normal and otosclerotic osteoblastic cells: influence on thymidine and leucine uptake and incorporation.

Steroid hormones are able to influence the metabolism of bone tissue in vivo, but reports regarding their direct action on bone cells fail to agree. In this study, in vitro administration of 17 beta-estradiol, testosterone and corticosterone to normal and otosclerotic osteoblastic cells induced a drop in DNA synthesis in both populations, an increase in the neosynthesis of endocellular proteins in normal cells and a rise, mainly in proteins secreted into the medium, in otosclerotic cells. The fact that 3H-thymidine and 3H-leucine uptake were lower in otosclerotic than in normal cells suggests that the membrane permeability differs in the two populations and that steroids exert an influence on both isotope uptake and directly modulate DNA and protein synthesis.

Corticosterone↗

Marijuana smoking as a possible cause of tongue carcinoma in young patients.

A case of T1N0M0 carcinoma of the tongue in a male 23-year-old 'regular' marijuana smoker is described. Hemiglossectomy and complete bilateral neck dissection were carried out. No post-operative radiotherapy was given as the resection margins were histologically negative. The tumour recurred one year later in the left cervical region involving the mandible and surgery was again performed, but after three months, neck disease was still evident. The case described case implies the introduction of marijuana as a possible new risk factor in the development of oral cavity tumours. Resection of the primary lesion has to be as wide as possible even in T1 cases, due to the aggressive biological behaviour of such tumours in young subjects.

Adult↗

Relationships between middle latency auditory responses (MLR) and speech discrimination tests in the elderly.

74 subjects aged between 60 and 80 years underwent tonal audiometry, speech discrimination tests (phonetically balanced words, normal sentences and compressed sentences) and middle latency responses (MLRs) in order to evaluate possible correlations between behavioural and electrophysiological tests. The results showed that in elderly patients normal sentences are better understood than phonetically balanced words, that performances decrease dramatically when listening conditions became difficult, that auditory threshold seems to influence speech discrimination scores more than does age per se. MLRs seem to be unaffected both by age and by auditory threshold and Pa occurrence is a more reliable parameter than its latency. No correlation between speech discrimination tests and MLRs could be observed; on the contrary in the presence of abnormal speech discrimination tests the MLRs were almost normal and vice versa.

Aged↗

Auditory steady-state responses in the rabbit.

The authors have studied auditory brainstem (ABRs), middle latency (MLRs) and steady-state potentials (SSRs) in 15 adult male rabbits weighing between 2.5 and 3 kg in order to verify if SSRs are due to a mere superimposition of ABRs and MLRs or to a resonance phenomenon. Ten of them were awake while 5 were studied under urethane anesthesia. Acoustic stimuli consisted in 0.1-ms square-wave pulses delivered at presentation rates ranging between 1 and 80/s at a stimulus intensity of 80 dB p.e. SPL. Our data show that reliable auditory SSRs can be obtained in the rabbit at a presentation rate of 30 stimuli/s, probably due to the superimposition of ABRs and MLR Pb waves which show an interwave interval of about 35 ms. The nonlinear aspects which can be detected are probably due to the effect of decreasing interstimulus intervals on the duration and amplitude of the Pb wave. It can then be concluded that SSRs in the rabbit are due more to a superimposition of ABR and MLR waves than to a resonance phenomenon.

Acoustic Stimulation↗

40-Hz steady-state responses in newborns and in children.

The authors investigated the 40-Hz steady-state responses (SSR) in 32 full-term newborns and in 10 normal children (5-8 years old), using 500-Hz tone bursts. The 40-Hz SSR threshold is located at about 50 and 30 dB nHL in newborns and older children, respectively. The latencies of both P1 and N1 waves decreased significantly with age, while the amplitudes increased. No significant latency and amplitude intersex differences have been observed. Moreover, with age, the 40-Hz SSR became more stable, their test-retest replicability improved, and P1-N1 wave occurrence increased. The authors finally discuss the possible underlying mechanisms of these findings and conclude that the 40-Hz SSR are difficult to obtain and are scarcely reliable in defining the low-frequency threshold in newborns. The stability and reliability of the responses increase with age, and the electrophysiological and behavioral thresholds to low-frequency stimuli tend to overlap.

Audiometry, Evoked Response↗

Altered adenylate cyclase activity in human otosclerotic bone cell cultures.

Adenylate cyclase (AC) activity was studied in whole homogenates of normal and otosclerotic bone cell cultures. When Mn2+ or Ca2+ was added to the medium there was a similar increase in AC activity in both cell types. F- provoked a greater rise in normal than in pathological cells, whereas 0.01 mM guanosine triphosphate (GTP) significantly raised cAMP synthesis in otosclerotic cells only. Mn2+ + calcitonin (Ct) increased AC activity in both cell preparations. With Ca2+ as cofactor there was no significant rise in either normal or pathological cells. However, while the combination Ca2+ + Ct + GTP had little effect on normal cells, it markedly increased cAMP synthesis in the pathological cells. 1 microgram/ml of the beta-blocker propranolol inhibited the effect Ct exerts on AC in normal cells, but enhanced it in otosclerotic cells. It would, therefore, seem that the pathogenesis of otosclerosis could be associated with an alteration in the AC system associated with Ct receptors.

Adenylyl Cyclases↗

Microbial flora of surface versus core tonsillar cultures in recurrent tonsillitis in children.

Surface and 'core' tonsillar specimens were collected from 60 children, between 2 and 14 years of age, suffering from recurrent tonsillitis, in order to establish the reliability of surface tonsillar swabbing technique and to define the most frequently involved aerobic and anaerobic microorganisms. From the qualitative point of view, the same mixed aerobic and anaerobic flora were obtained in both samples thus demonstrating the reliability of the surface swabbing technique. From the quantitative point of view, 187 microorganisms, 129 (69.2%) aerobes and 58 (30.8%) anaerobes were isolated from surface cultures while 184, 109 (59.2%) aerobes and 75 (40.8%) anaerobes from the core cultures, thus demonstrating a greater number of anaerobes in the core of the tonsil. The most common isolated aerobic microorganisms were the alpha- and beta-hemolytic Streptococci, the Neisseriae and the Staphylococcus aureus; the predominant anaerobic ones were the Fusobacterium nucleatum, the Bacteroides sp. and the Veillonella parvula. The isolated staphylococcus aureus and the bacteroides sp. were all beta-lactamase producers.

Adolescent↗

Auditory brainstem responses in noise-induced permanent hearing loss.

Fifty-four patients (108 ears) with presumed noise-induced hearing loss, were subjected to tonal and speech audiometry, impedance tests and measurements of auditory brainstem responses (ABR), in order to check for possible retrocochlear involvement. ABR data indicated that latency values of waves I, III and V, as well as III-I, V-III and V-I intervals fell within the normal range in all cases (M +/- 2 SD), even for fast repetition rates (51 stim/s). Poor waveform resolution of early components, particularly of wave I, was found in 12 ears (11.1%) and a total absence of evoked potentials not always related to the hearing loss, occurred in 5 ears (4.6%).

Acoustic Impedance Tests↗