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Biomedical subjects

L Giordano

Publications and source records attributed to L Giordano.

At least 37 records · Page 2Linked to original sources

3-Arylsulphonyl-5-arylamino-1,3,4-thiadiazol-2(3H)ones as anti-inflammatory and analgesic agents.

Two series of 3-arylsulphonyl-5-arylamino-1,3,4-thiadiazol-2(3H)ones 2 with potential anti-inflammatory and analgesic activity were prepared and tested. Pharmacological results revealed that all the title compounds, endowed with an arylsulphonyl side chain, possess good antalgic activity and fair anti-inflammatory properties. The analgesic profile of the two series, evaluated by the acetic acid writhing test, showed that compounds 2c, 2f and 2h, in particular, were the most active. Structure-activity relationships are briefly discussed.

Analgesics↗

Prostaglandin E2 signalling pathway in human T lymphocytes from healthy and conjunctiva basal cell carcinoma-bearing subjects.

Prostaglandin E-induced signal transduction pathways in human T cells from healthy and uveal melanoma-bearing subjects were studied. Transfection experiments showed that PGE2 was able to phosphorylate and activate the fusion trans-activator of the cAMP responsive element-binding protein (CREB). Phosphorylation was at least partially mediated by protein kinase A, as evidenced by the effects of specific kinase inhibitors. Western blotting experiments, which were performed to identify the CREB/ATF2 family members involved in the response to PGE2, revealed a modulation of proteins CREB1, CREB2 and ATF2 and phosphorylation of the 43 kDa form of CREB. Experiments of immunoprecipitation with CREB-binding protein (CBP) demonstrated that, after PGE2 treatment, all of the CREB/ATF isoforms studied, as well as the phosphorylated form of CREB (p-CREB), interacted with CBP. In basal conditions, T cells from patients with conjunctiva basal cell carcinoma showed the presence of p-CREB, which coimmunoprecipitated with CBP. CREB phosphorylation did not modify after PGE2 treatment whereas the p-CREB fraction bound to CBP increased in a delayed manner compared to normal subjects.

Activating Transcription Factor 2↗

Seckel's syndrome and malformations of cortical development: report of three new cases and review of the literature.

Seckel's syndrome is a rare form of primordial dwarfism, characterized by peculiar facial appearance. In the past, this condition was overdiagnosed, and most attention was given to the facial and skeletal features to define more precise diagnostic criteria. The presence of mental retardation and neurologic signs is one of the peculiar features of this syndrome, but only recently were rare cases of malformation of cortical development described, as documented by magnetic resonance imaging (MRI). Here, we present three new cases of Seckel's syndrome showing different malformations of cortical development (one gyral hypoplasia, one macrogyria and partial corpus callosum agenesis, and one bilateral opercular macrogyria). We hypothesize that the different types of clinical expression of our patients could be explained by different malformation of cortical development types. We think that MRI studies could be performed in malformative syndromes because of the possible correlations between type and extent of the lesion and the clinical picture of any individual case.

Abnormalities, Multiple↗

Interleukin-1beta regulates CFTR expression in human intestinal T84 cells.

Cystic fibrosis is an autosomal recessive genetic disease, produced by a mutation in the CFTR gene that impairs its function as a chloride channel. In this work, we have examined the effects of interleukin-1beta (IL-1beta) on the expression of CFTR in human colonic T84 cells. Treatment of T84 cells with IL-1beta (0.25 ng/ml) for 4 h resulted in an increased CFTR expression (mRNA and protein). However, higher doses of IL-1beta (1 ng/ml and over) produced inhibition of CFTR mRNA and protein expression. The protein kinase C (PKC) inhibitors H7 (50 microM) and GF109203X (1 microM) inhibited the stimulatory effect of IL-1beta. Similar effects were seen in the presence of the protein tyrosine kinase (PTK) inhibitors genistein (60 microM) and herbymicin A (2 microM). These results suggest that some PKC isoform(s) and at least a PTK might be involved in the CFTR up-regulation induced by IL-1beta. The repression of CFTR up-regulation by cycloheximide (35.5 microM) suggests the participation of a de novo synthesized protein. Results obtained by using the RNA polymerase II inhibitor DRB (78 microM), suggest that the increased mRNA levels seen after IL-1beta treatment are not due to an increased stability of the message. We conclude that the CFTR mRNA and protein levels are modulated by IL-1beta, this cytokine being the first extracellular protein known to up-regulate CFTR gene expression.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

[Functional results in the reconstruction of the ossicular chain in partial or total atrophy of the incus. Comparison between reconstruction using a moulded incus and hydroxyapatite PORP].

Ossicular chain defects modifying sound transmission through the middle ear can be treated with (re)implantation of remodeled autologous o homologous ossicles. In recent years, thanks to improved biocompatibility of the materials on the market, prostheses have been increasingly used in the partial or total ossicular chain reconstruction. The present study evaluates auditory ossicle reconstruction as a result of partial or total atrophy of the incus, comparing the use of the remodeled autologous incus with the use of partial hydroxyapatite prostheses (PORP). The study involved 79 patients of which 59 (74.7%) underwent ossicular chain reconstruction using a remodeled, inverted autologous incus while in the remaining 20 cases (25.3%) a hydroxyapatite prosthesis (PORP) was used. The effectiveness of the ossicular chain was evaluated by comparing pre- and postoperative audiometry and evaluating the average thresholds at frequencies of 0.5, 1, 2 and 3 KHz. The average preoperative audiometric gap (understood as the relationship between the air-bone gap) was 23 dB (Standard Deviation 11.2) while postoperatively it was 11 dB (SD 8.5) (p < 0.0001). Therefore the improvement in the air-bone gap was 12 dB (SD 11) for the overall population: 13 dB (SD 10) in those cases where reconstruction was performed using a remodeled incus and 8 dB (SD 11) when PORP was used. The postoperative cumulative gap between the air and bone pathways fell between 0 and 20 dB in 84% of the total population: 89% of those reconstructed with a remodeled incus and 73% of those using PORP. The middle ear ossicular chain reconstruction was performed using remodeled, inverted autologous incus in those cases where ossicular damage did not compromise its use while prostheses made of a biocompatible material (hydroxyapatite PORP) were reserved for those cases where the incus was absent or severely worn. The results obtained are satisfactory, remained stable in time and reflect the average values reported in the Literature.

Adolescent↗

Benign infantile familial convulsions: natural history of a case and clinical characteristics of a large Italian family.

We present a patient (3 months old) with partial and generalized seizures who has a family history of seizures with a onset during the first 12 months of life. We diagnosed benign infantile familial convulsions (BIFC) and we did not introduce any antiepileptic therapy. We present clinical data of her family where 18 out of 35 members were affected; to our knowledge this is the largest family with BIFC. BIFC is transmitted as an autosomal dominant trait; recently it has been reported that the gene for BIFC maps to the long arm of chromosome 19. We conducted linkage analysis in our family providing significant exclusion of linkage between the BIFC locus phenotype and chromosome 19 markers, suggesting that a second locus is involved in this family.

Child, Preschool↗

No evidence of a major locus for benign familial infantile convulsions on chromosome 19q12-q13.1.

PURPOSE: A locus for benign familial convulsions (BFICs) has been recently mapped on chromosome 19q12-13.1 by studying five families of Italian descent. The main goal of this study was to investigate the role of this locus in a set of seven newly identified families with at least three affected cases. METHODS: Five polymorphic microsatellite markers covering the BFIC locus on chromosome 19q have been typed, and parametric linkage analysis has been performed to analyze the segregation of the BFIC locus within our families. RESULTS: Cumulative 2-point lod scores and multipoint analysis showed no evidence of linkage between chromosome 19 markers and the BFIC phenotype. The analysis of family-specific 2-point lod scores and haplotypes, however, indicated the presence of linkage to chromosome 19q in a single family, suggesting genetic heterogeneity within our family sample. CONCLUSIONS: Our study demonstrates that the previously reported BFIC locus on chromosome 19q12-13.1 is not a major locus for BFICs. We suggest that genetic heterogeneity may have generated our discordant linkage findings, as it was reported in benign familial neonatal convulsions, a related idiopathic mendelian syndrome.

Chromosome Mapping↗

Distribution of photon absorption rates across the rat retina.

1. An investigation into the distribution of light intensity across the rat retina was carried out on excised, intact rat eyes exposed to Ganzfeld illumination from a helium-neon laser (543 nm). 2. Some of the light entering the eyes exits through the sclera where its intensity can be monitored with an optical 'pick-up' that samples the intensity coming from a small region of external sclera and underlying retina. The spatial resolution of the pick-up is such that it samples light that has passed through ca 2 % of the rods in the rat eye. 3. Some of the laser light is absorbed by the rod pigment, rhodopsin, which gradually bleaches. Bleaching in the retina, in turn, causes an exponential increase in intensity emanating from the sclera. By monitoring this intensity increase, we are able to measure two important parameters in a single bleaching run: the local rhodopsin concentration and the local intensity falling on the rods. 4. With an ocular transmission photometer, we have measured both the local intensity and the local rhodopsin concentration across wide regions of rat retina. Both pigmented and albino rats were studied. 5. The distributions of rhodopsin and intensity were both nearly uniform; consequently, the product, (rhodopsin concentration) x (intensity), was similarly nearly equal across the retina. This means that the initial rate of photon absorption is about the same at all retinal locations. 6. Interpreted in terms of photostasis (the regulation of daily photon catch), this means that the rate of photon absorption is about the same in each rod, viz. 14 400 photons absorbed per rod per second. Since this rate of absorption is sufficient to saturate the rod, one possible purpose of photostasis is to maintain the rod system in a saturated state during daylight hours.

Albinism↗

Benign partial epilepsy in infancy with complex partial seizures (Watanabe's syndrome): 12 non-Japanese new cases.

International epilepsy classification includes different epileptic syndromes with favourable outcomes in pediatric age. In addition to these, other forms probably exist and in various papers in international literature they are proposed as new entities. This article presents a survey of benign complex partial epilepsy in infancy, a new epileptic syndrome first proposed by Watanabe, in 1987. Our work represents the only description of non-Japanese cases although similar but familial cases had been referred by Vigevano in 1992. We present data for 12 children (aged up to 9 years) followed over 2 years who had all the typical clinical features characterizing Watanabe's cases. For all of them we obtained EEG seizure recordings demonstrating the partial nature of their fits, arising from occipital or temporal regions. Interictal EEG were completely normal, both in waking and sleep. Evolution demonstrated benign outcome and all the children are seizure-free (eight of them have already stopped all medication) and all have normal psychomotor development.

Age of Onset↗

Establishment and characterization of a megakaryoblast cell line with amplification of MLL.

A new cell line with megakaryoblastic features, designated UoC-M1, was established from the malignant cells of a 68-year-old patient with acute myeloid leukemia. The patient's leukemic cells reacted with alpha-naphthyl acetate esterase and acid phosphatase and expressed CD7, CD24, CD34, CD38, CD45, HLA-DR and CD61. Cytogenetic analysis of the patient's malignant cells (and of the UoC-M1 cells) showed a human, male hypodiploid karyotype with many chromosome rearrangements and marker chromosomes. Spectral karyotyping (SKY) analysis complemented the G-banded karyotyping and clarified several chromosomal translocations and identified the marker chromosomes. Fluorescence in situ hybridization (FISH) and SKY analysis demonstrated that one marker chromosome contained three segments of chromosome 9 interspersed with three segments of chromosome 11, as well as a portion of chromosome 19. FISH analysis with a probe for MLL revealed that the UoC-M1 cells contained four copies of the MLL gene. Southern blot analysis determined that the MLL gene had a germline profile while Northern and Western analyses showed that the MLL mRNAs and protein were of the appropriate sizes. This is the first report of amplification of the MLL gene which may be an additional mechanism of leukemogenesis or disease progression.

Aged↗

[Myringoplasty in children: a comparison with an adult population].

The indications for myringoplasty in children has always been a controversial subject since many authors feel the high frequency of the phlogistic auricular processes in children constitute an unfavorable prognostic factor to success of the procedure. The authors present the results obtained in 23 patients under 17 years of age who had undergone myringoplasty for simple perforation of the tympanum. In cases of posterior and inferior perforations, surgery was performed using the underlay technique and a transmeatal approach; in all other cases the overlay technique was used with a retroauricular approach. An average 30 month follow-up (range 12-55 months) revealed new perforations in only 2 cases (9%). From the functional point of view the average air/bone conduction gap was reduced to 10 dB. As a control, the results were compared to those obtained in 150 patients over 16 years of age, again affected by simple perforation of the tympanic membrane and treated by myringoplasty using the same methods. In the adults, 22 new perforations were found (15%) while the functional results were analogous to those obtained in the children group. In this light, it can be asserted that myringoplasty can be considered a safe procedure to be used in children and it does not appear essential to wait until they have finished growing before performing this procedure.

Adolescent↗

Growth inhibition of B-cell precursor acute lymphoblastic leukemia cell lines by monocytes: a role for prostaglandin E2.

Leukemic cell lines have proven invaluable in the molecular analysis of recurring chromosomal translocations but the optimal methods for leukemia cell line establishment are unknown. During in vitro culture, most B-cell precursor acute lymphoblastic leukemia (BCP-ALL) cells die within 1 week at least partially mediated by inhibitors elaborated by peripheral blood mononuclear cells (PB MNCs) present within the leukemia sample. In experiments reported here, cyclooxygenase inhibitors (indomethacin and meclofenamic acid) blocked the PB MNC-mediated inhibition of BCP-ALL proliferation. Also, prostaglandin E2 (PGE2) was detected in supernatants from PB MNC cultures. When PGE2 was mixed directly with BCP-ALL cells, proliferation decreased significantly. Under the culture conditions used, PB MNCs secreted PGE2 which appears to be one of the major inhibitors of BCP-ALL growth in vitro.

Adult↗

Interaction of spontaneous and organised screening for cervical cancer in Turin, Italy.

In a screening programme for cervical cancer, coverage of the target population is a major determinant of effectiveness and cost-effectiveness and is one of the parameters for programme monitoring recommended by the "European Guidelines for Quality Assurance". An organised screening programme was started in Turin, Italy, in 1992. Spontaneous screening was already largely present, but coverage (proportion of women who had at least a test within 3 years) was low (< 50%) and distribution of smears uneven. No comprehensive registration of spontaneous smears was available. All women were invited for the first round, independently of their previous test history. Coverage was estimated by integrating routine data from the organised programme with data on spontaneous screening obtained by interviews of a random sample of 268 non-compliers to invitation and 167 compliers. Overall (spontaneous + organised) coverage was estimated to be 74% (95% CI, 71-78%). The proportion of the target population covered as an effect of invitation was estimated to be 17% (95% CI, 15-20%). Invitations were successful in increasing coverage in previously poorly screened groups. Although 20-25% of compliers was estimated to have had further tests before the end of the round, we estimated that switching to a 3-year interval saved approximately 0.26 tests per complier. This suggests that invitations to an organised programme even to previously covered women, can be a cost-effective policy. Our method of estimating overall coverage can be useful in many other European areas where a comprehensive registration of smears is not available.

Adult↗

Certified first responder: a comprehensive model for pediatric training.

The purpose of this document is to present a general approach to educating the First Responder in Emergency Pediatric Care. The First Responder is especially important in the emergency care of the sick or injured child. The majority of mortality and morbidity associated with pediatric emergencies is a result of airway and ventilatory compromise. In addition, most airway and ventilation problems can be corrected with only basic life support interventions that are within the scope of practice of the First Responder. As a result, it is of paramount importance to assure that the First Responder is adequately trained in the initial care of the pediatric patient. This document will review some of the key objectives and topics which the First Responder needs to understand in order to adequately care for children until further emergency care arrives. Templates for lesson plans and suggested activities for training the First Responder are also presented.

Certification↗

[Evaluation of the cochlear aqueduct patency: comparison of 2 noninvasive techniques].

Variations in cephalo-rachidian fluid pressure can be transmitted to the middle ear through the cochlear aqueduct (CA). This gives us a non-invasive manner to evaluate any changes in fluid pressure by measuring middle ear impedance (impedancemetry). The present study compared two indirect methods for measuring intracranial pressure: a) impedancemetry during evoked jugulo-tympanic reflex (JTR) and b) study of the tympanic membrane (TM) fine motility using a MMS-10 analyzer. The latter is a new procedure involving the indirect evaluation of the fluid pressure. In fact, when the CA is open the labyrinthine fluid pressure is transmitted to the oval window, the stapes platina and, finally, to the tympanic membrane where it can be measured with an MMS-10 unit. This equipment can measure nanoliter shifts in the TM. In particular, comparison between the clinostatic and orthostatic tympanic motility measurements enable one to establish whether the CA is patent or not. In the present study 15 subjects were examined using both a) impedancemetry during jugular compression and b) analysis of the TM shift using an MMS-10 unit. In 14 of the 15 cases there was good correlation between the data obtained using both methods: in all but one case it proved possible to record a JTR-induced variation in impedance whenever the MMS-10 indicated that the CA was open. The results suggest that, in clinical practice, the two methods can be used in parallel for non-invasive monitoring of variations in intracranial pressure in patients with neurological involvement. On the other hand, in the E.N.T. field these techniques could be used to study inner ear pathologies causing dynamic alterations of the endolabyrinth fluids (endolymphatic hydrops, labyrinthine fistula).

Acoustic Impedance Tests↗