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Biomedical subjects

R Barone

Publications and source records attributed to R Barone.

At least 37 records · Page 2Linked to original sources
PubMed1999

Plasma chitotriosidase activity in patients with beta-thalassemia.

Chitotriosidase, a macrophage marker, which is extremely increased in plasma of Gaucher patients, was measured in patients with beta-thalassemia, an haematological disorder characterized by the genetic defect of beta-globin chains synthesis resulting in unproductive erythropoiesis and enormous expansion of the reticuloendothelial system. Plasma chitotriosidase was increased to a variable extent in 13 of 70 patients with beta-thalassemia major treated with the intense transfusion regimen and iron chelation therapy. It was normal in 22 and slightly elevated in 3 subjects with beta-thalassemia intermedia which were not transfused. The highest levels of plasma chitotriosidase, as high as in Gaucher patients, were found in 7 (10%) of the beta-thalassemia major patients which also had the highest degree of iron overload as judged by their serum ferritin level (> 3000 ng/ml), high SGPT level and elevated urinary iron excretion. To our knowledge, beta-thalassemia is hitherto the only disorder in which an increase of plasma chitotriosidase, comparable to that seen in Gaucher disease, may occur. The increase of plasma chitotriosidase activity in beta-thalassemia patients with high iron overload, could be related to an iron mediated damage to the lysosomal apparatus. In addition, similarly to Gaucher disease, the increased chitotriosidase production in beta-thalassemia might reflect macrophage activation probably related to the intracellular iron overload, storage of erythrocytes membrane break-down products and oxidation of excess alpha-hemoglobin subunits. Further studies are required to define the role of chitotriosidase evaluation to assess the efficacy of chelation therapy in reducing the macrophage activation due to intracellular iron overload in beta-thalassemia.

Adolescent↗
PubMed1999

Developmental patterns and neuropsychological assessment in patients with carbohydrate-deficient glycoconjugate syndrome type IA (phosphomannomutase deficiency).

Carbohydrate-deficient glycoconjugate (CDG) syndrome type I due to phosphomannomutase deficiency (CDGIA) is the most common among a group of metabolic disorders characterized by a defective glycosylation of glycoconjugates. Clinically it is a multisystem disease with an important involvement of the central nervous system including pontocerebellar atrophy. Here the developmental patterns and results of neuropsychological assessment of four young adults with CDGIA syndrome are reported. The patients, aged 14-26 years, had classical clinical findings of CDGIA syndrome and olivopontocerebellar atrophy of severe degree. They had a marked delay in all areas of psychomotor development and gained to walk with aid, perform manipulative abilities and develop a communicative language after the 7th year. Later on, the acquired abilities remained stable, while self-help skills gradually improved, allowing the patients to join the family life. On neuropsychological assessment, there was mental retardation of variable degree with a special impairment of visuoperceptual skills, visuospatial organization, eye-hand coordination, verbal memory and language. Such findings, may be partially explained by the supratentorial atrophy in our patients and add more evidences to the role of the cerebellum and brainstem in the acquisition of non-motor cognitive functions. This study expands our understanding on the clinical spectrum of CDGIA syndrome and may be helpful for planning rehabilitation and education.

Adolescent↗
PubMed1999

Peripheral lymphocyte subsets and other immune aspects in Rett syndrome.

A possible role of the immune system in the pathogenesis of some neurologic disorders, including infantile autism, was recently postulated. This observation prompted the authors to investigate some immunologic aspects in a group of patients with Rett syndrome, a disorder still not completely clarified but with some points of commonality with infantile autism. Humoral and cell-mediated immunity were investigated in 20 females with Rett syndrome. Peripheral lymphocyte subsets revealed a reduced percentage of CD8+ suppressor-cytotoxic cells in all of the patients with Rett syndrome, resulting in an increased CD4+/CD8+ ratio. In addition, 15 (75%) of the 20 patients had low levels of natural killer cells. Soluble interleukin-2 receptor was elevated in the youngest patients. Antineuronal and antimyelin ganglioside antibodies were absent, as were antinuclear antibodies, antistriated muscle antibodies, and antismooth muscle antibodies. Immunoglobulin fractions and complement were normal for age in all of the patients.

Adolescent↗
PubMed1999

Purification and characterization of a lipoxygenase enzyme from durum wheat semolina.

Purification of a lipoxygenase enzyme from the cultivar Tresor of durum wheat semolina (Triticum turgidum var. durum Desf) was reinvestigated furnishing a new procedure. The 895-fold purified homogeneous enzyme showed a monomeric structure with a molecular mass of 95 +/- 5 kDa. Among the substrates tested, linoleic acid showed the highest k(cat)/K(m) value; a beta-carotene bleaching activity was also detected. The enzyme optimal activity was at pH 6. 8 on linoleic acid as substrate and at pH 5.2 for the bleaching activity on beta-carotene, both assayed at 25 degrees C. The dependence of lipoxygenase activity on temperature showed a maximum at 40 degrees C for linoleic acid and at 60 degrees C for bleaching activity on beta-carotene. The amino acid composition showed the presence of only one tryptophan residue per monomer. Far-UV circular dichroism studies carried out at 25 degrees C in acidic, neutral, and basic regions revealed that the protein possesses a secondary structure content with a high percentage of alpha- and beta-structures. Near-UV circular dichroism, at 25 degrees C and at the same pH values, pointed out a strong perturbation of the tertiary structure in the acidic and basic regions compared to the neutral pH condition. Moreover, far-UV CD spectra studying the effects of the temperature on alpha-helix content revealed that the melting point of the alpha-helix is at 60 degrees C at pH 5.0, whereas it was at 50 degrees C at pH 6.8 and 9.0. The NH(2)-terminal sequence allowed a homology comparison with other lipoxygenase sequences from mammalian and vegetable sources.

Amino Acid Sequence↗
PubMed1999

Clinical and neuroradiological follow-up in mucopolysaccharidosis type III (Sanfilippo syndrome).

Mucopolysaccharidosis type III (Sanfilippo syndrome) is an autosomal recessive disorder characterised by progressive nervous system involvement with mental retardation, behavioural problems and seizures. Three patients, of 20 months to 12 years of age, were followed up for 3 years both clinically and by using brain magnetic resonance imaging (MRI). Our results suggest that in MPS III patients MRI findings, including atrophy and abnormal or delayed myelination, may precede the onset of overt neurological symptoms. The increasing neurological morbidity is accompanied by different degrees of progressive atrophic changes, mainly affecting the cerebral cortex and the corpus callosum. However, it appears that, across subjects, the rate of MRI changes is unrelated to the severity of the clinical phenotype. On this basis it could be argued that in MPS III the worsening of the neurological symptoms might not necessarily reflect only the progressive cerebral abnormalities detectable by MRI.

Atrophy↗
PubMed1999

Point mutations throughout the GLI3 gene cause Greig cephalopolysyndactyly syndrome.

Greig cephalopolysyndactyly syndrome, characterized by craniofacial and limb anomalies (GCPS; MIM 175700), previously has been demonstrated to be associated with translocations as well as point mutations affecting one allele of the zinc finger gene GLI3. In addition to GCPS, Pallister-Hall syndrome (PHS; MIM 146510) and post-axial polydactyly type A (PAP-A; MIM 174200), two other disorders of human development, are caused by GLI3 mutations. In order to gain more insight into the mutational spectrum associated with a single phenotype, we report here the extension of the GLI3 mutation analysis to 24 new GCPS cases. We report the identification of 15 novel mutations present in one of the patient's GLI3 alleles. The mutations map throughout the coding gene regions. The majority are truncating mutations (nine of 15) that engender prematurely terminated protein products mostly but not exclusively N-terminally to or within the central region encoding the DNA-binding domain. Two missense and two splicing mutations mapping within the zinc finger motifs presumably also interfere with DNA binding. The five mutations identified within the protein regions C-terminal to the zinc fingers putatively affect additional functional properties of GLI3. In cell transfection experiments using fusions of the DNA-binding domain of yeast GAL4 to different segments of GLI3, transactivating capacity was assigned to two adjacent independent domains (TA(1)and TA(2)) in the C-terminal third of GLI3. Since these are the only functional domains affected by three C-terminally truncating mutations, we postulate that GCPS may be due either to haploinsufficiency resulting from the complete loss of one gene copy or to functional haploinsufficiency related to compromised properties of this transcription factor such as DNA binding and transactivation.

Animals↗
PubMed1999

Magnetic fields increase cell survival by inhibiting apoptosis via modulation of Ca2+ influx.

Static magnetic fields with intensities starting from 6 gauss (6x10(-4) tesla, T) were found to decrease in an intensity-dependent fashion, reaching a plateau at 6 x 10(-3) T, the extent of cell death by apoptosis induced by several agents in different human cell systems. This is not due to a change in the mode of cell death (i.e., to necrosis) or to a delay of the process itself; rather, the presence of magnetic fields allows the indefinite survival and replication of the cells hit by apoptogenic agents. The protective effect was found to be mediated by the ability of the fields to enhance Ca2+ influx from the extracellular medium; accordingly, it was limited to those cell systems where Ca2+ influx was shown to have an antiapoptotic effect. Magnetic fields thus might interfere with human health by altering/restoring the equilibrium between cell death and proliferation; indeed, the rescue of damaged cells may be the mechanism explaining why magnetic fields that are not mutagenic per se are often able to increase mutation and tumor frequencies.

Animals↗
PubMed1999

Rett syndrome: photographic evidence of rapid regression.

Rett Syndrome is known to occur in females, around the second year, with loss of hand use, onset of stereotypes and acquired microcephaly. Such regression is often very rapid, but this has never been documented. In one of our patients, photographs taken at different times clearly demonstrate the rapid progression of first symptoms. Moreover, in the present case, the occurrence of a febrile illness, which preceded the onset of the neurological picture, support the hypothesis that environmental factors may trigger the onset of Rett Syndrome in genetically predisposed subjects.

Adolescent↗
PubMed1999

Interleukin 2 gene therapy of colorectal carcinoma with autologous irradiated tumor cells and genetically engineered fibroblasts: a Phase I study.

The purpose of this study was to determine the safety, toxicity, and antitumor immune response following S.C. immunizations with a mixture of irradiated, autologous tumor cells and autologous fibroblasts that were genetically modified to express the gene for interleukin 2 (IL-2) in patients with colorectal carcinoma. Ten patients were treated with a fixed dose of tumor cells (10(7)) and escalating doses of fibroblasts secreting IL-2 (per 24 h): 100 units (three patients), 200 units (three patients), 400 units (three patients), and 800 units (one patient). Pre- and posttreatment peripheral blood mononuclear cells were evaluated for evidence of antitumor immune responses. Fatigue and/or flu-like symptoms were experienced by seven patients and delayed-type hypersensitivity-like skin reactions were observed at the sites of the second or subsequent vaccinations in five patients. Low frequencies of tumor cytotoxic T-cell precursors (range, 1/190,000-1/1,320,000 peripheral blood mononuclear cells) were detected prior to therapy in four of seven patients. There was a 5-fold increase following treatment in the frequency of tumor cytotoxic T-cell precursors in two of six evaluable patients. Some patients with colorectal cancer have low frequencies of tumor cytotoxic T-cell precursors that may be increased by this well-tolerated form of IL-2 gene therapy, which warrants continued clinical evaluation.

Cancer Vaccines↗
PubMed1999

Localized soft tissue ridge augmentation at phase 2 implant surgery: a case report.

A case of congenitally missing maxillary lateral incisors is presented to illustrate a modification of Abrams's roll technique. Buccal releasing incisions are avoided by using an intrasulcular incision on the adjacent teeth. The tissue overlying the cover screw is transferred between the buccal cortical bone and the buccal masticatory mucosa, thus correcting the localized buccal ridge atrophy.

Adult↗
PubMed1998

Prognostic relevance of pancreatic uptake of technetium-99m labelled human polyclonal immunoglobulins in patients with type 1 diabetes.

Insulin-dependent type 1 diabetes (IDDM) is caused by the autoimmune destruction of insulin-producing beta cells. Approximately 10%-20% of patients may benefit from adjuvant immunotherapy upon diagnosis of the disease in order to protect residual beta-cell function. It has been suggested that this subgroup of patients differs from others by virtue of the presence of residual pancreatic inflammation and beta-cell function. In this study we have investigated to what extent technetium-99m-labelled human polyclonal immunoglobulins (99mTc-HIG) accumulate in the pancreas of IDDM patients at the time of diagnosis and 1 year thereafter, with a view to ascertaining whether HIG scintigraphy is useful for the identification of IDDM patients with residual pancreatic inflammation. Patients with recent-onset IDDM (n=15) were investigated at the time of diagnosis and 1 year later, and ten age- and sex-matched normal subjects were also studied. Gamma camera imaging and target to background ratio, analysed blind by three independent readers, were used to quantify the radioactivity in the pancreatic region and findings were correlated with metabolic, immunological and clinical parameters. Seven out of 15 newly diagnosed IDDM patients showed a significant accumulation of radiolabelled HIG in the pancreas (pancreas/bone ratio higher than the mean +2SD of normal subjects). One year after diagnosis, pancreatic accumulation of HIG was still detectable in most IDDM patients who were positive at the time of diagnosis. Six out of seven patients with positive scintigraphy had a partial clinical remission. These results indicate that HIG scintigraphy at the time of onset of diabetes identifies a subset of patients with residual beta-cell function who may benefit from adjuvant immunotherapy.

Adolescent↗
PubMed1998

Lysosomal enzyme activities in serum and leukocytes from patients with carbohydrate-deficient glycoprotein syndrome type IA (phosphomannomutase deficiency).

From 10 patients with carbohydrate-deficient glycoprotein (CDG) syndrome due to phosphomannomutase (PMM) deficiency, out of 10 lysosomal enzymes, 7 enzyme activities were measured in serum and 9 in leukocytes. In serum there was a 2-fold to 4-fold increase in activity of beta-glucuronidase, beta-hexosaminidase, beta-galactosidase, and arylsulphatase A. In leukocytes, however, several enzymes had reduced activity, particularly alpha-fucosidase, beta-glucuronidase and alpha-mannosidase. These abnormalities could result from missorting, defective reuptake and/or reduced stability of the enzymes due to the defective glycosylation.

Congenital Disorders of Glycosylation↗
PubMed1998

A protocol for maintaining or increasing the width of masticatory mucosa around submerged implants: a 1-year prospective study on 53 patients.

Masticatory mucosa around implants may be useful to enhance esthetics and/or plaque control. This study proposes simplified guidelines for maintaining or obtaining a minimal amount of masticatory mucosa around submerged implants in cases of partial edentulism, and for keeping the need for additional surgery to a minimum. Free gingival grafts were used in the mandibular arch when the width of buccal masticatory mucosa was less than 2 mm. The width of masticatory mucosa expected to be available for attachment to the bone surface buccal to implants was estimated by measuring the distance between the emergence of the implant from bone and the mucogingival junction. When this distance was 3 mm or less, the use of an apically positioned flap for implant exposure was preferred over gingivectomy. The amount of masticatory mucosa buccal to implants was measured 2 weeks, 6 months, and 12 months after implant exposure. In no case was the width of masticatory mucosa less than 2 mm at 1 year. Therefore, this protocol is recommended for the treatment of cases where the presence of an adequate amount of masticatory mucosa is necessary to ensure a satisfying appearance or is useful for facilitating oral hygiene.

Adult↗
PubMed1997

Two new mild homozygous mutations in Gaucher disease patients: clinical signs and biochemical analyses.

Gaucher disease (GD) is a lysosomal storage disorder resulting from impaired activity of lysosomal beta-glucocerebrosidase. More than 60 mutations have been described in the GBA gene. They have been classified as lethal, severe, and mild on the basis of the corresponding phenotype. The fact that most GD patients are compound heterozygous and that most type 1 patients bear the N370S allele, which by itself causes a mild phenotype, make it difficult to correlate the clinical signs with the mutations. Besides N370S, about 10 mild mutations have been described, but only one undoubtedly classified as mild was found at homozygosity. Here we report 2 novel mutations, I402T and V375L, at homozygosity in 2 adult Italian type 1 GD patients. Some properties of the I402T fibroblast enzyme have been compared to those of the enzyme from cells of several N370S/N370S patients. Analysis of the catalytic properties and heat stability as well as the response to phosphatidylserine and sphingolipid activator protein indicate a marked similarity between the 2 enzymes. The finding of another, unrelated patient bearing the I402T mutation (in this case as a compound heterozygote with mutation N370S) suggests that this allele might be quite frequent in the area of Sicily from where both patients originated. In conclusion, the phenotypic expression in the 2 homozygous patients presented here and the biochemical data for one of them allowed the classification of these mutations as mild thus extending the group of mild mutations found at homozygosity.

Adult↗
PubMed1997

Effects of temperature and SDS on the structure of beta-glycosidase from the thermophilic archaeon Sulfolobus solfataricus.

The effects of temperature and SDS on the three-dimensional organization and secondary structure of beta-glycosidase from the thermophilic archaeon Sulfolobus solfataricus were investigated by CD, IR spectroscopy and differential scanning calorimetry. CD spectra in the near UV region showed that the detergent caused a remarkable change in the protein tertiary structure, and far-UV CD analysis revealed only a slight effect on secondary structure. Infrared spectroscopy showed that low concentrations of the detergent (up to 0.02%) induced slight changes in the enzyme secondary structure, whereas high concentrations caused the alpha-helix content to increase at high temperatures and prevented protein aggregation.

Bacterial Proteins↗