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C Benelli

Publications and source records attributed to C Benelli.

At least 37 records · Page 2Linked to original sources
PubMed1997

Clinical review of 247 case records of Spitz nevus (epithelioid cell and/or spindle cell nevus).

BACKGROUND: Spitz nevus has clinically been described as a dome-shaped usually nonpigmented papular or nodular lesion variable in color from pink to red. OBJECTIVES: To give an exhaustive description of the clinical features of the Spitz nevus from a large series of 247 patients. METHODS: A retrospective analysis of the clinical features of 247 Spitz nevi excised from 1974 to 1993 has been performed. We evaluated the following features: age, sex, anatomical location, clinical and histopathologic features; descriptive statistics were calculated and relationships among the above variables were assessed. RESULTS: Most lesions were pigmented (71.7%), located on the lower extremities (43.3%), more frequent in the first decade (55.8%) and in females (57.9%). The nonpigmented type was more frequent in the head or neck region, whereas the pigmented types were more frequent on the lower extremities. Besides, these types showed different histopathologic features: the spindle cells usually predominated in the flat pigmented type, whereas dome-shaped types were usually composed of both spindle and epithelioid cells. CONCLUSIONS: In our patients, the pigmented Spitz nevi were more common than the nonpigmented ones; furthermore pigmented and nonpigmented Spitz nevi showed different anatomical locations and different histopathologic features.

Adolescent↗
PubMed1996

Mutation analysis of the pyruvate dehydrogenase E1 alpha gene in eight patients with a pyruvate dehydrogenase complex deficiency.

Most of the mutations causing deficiency of the pyruvate dehydrogenase (PDH) complex are in the X-linked E1 alpha gene. We have developed a rapid screening method for the detection of mutations in this gene using reverse transcription of total RNA, polymerase chain reaction amplification of the whole coding region of the gene and single-strand conformation polymorphism (SSCP) analysis. With this method, we studied eight patients with a PDH complex deficiency, using cultured fibroblasts. In all patients, aberrant SSCP patterns were found and, after sequencing of the corresponding fragments, we were able to identify six new mutations and two mutations already described previously. The mutations are point mutations leading to amino acid substitutions (5) and direct repeat insertions (3). The presence of the mutations was confirmed in genomic fibroblast DNA. The 4 female patients were shown to carry both a normal and a mutated E1 alpha gene.

Base Sequence↗
PubMed1994

Evidence for a role of protein kinase C in the activation of the pyruvate dehydrogenase complex by insulin in Zajdela hepatoma cells.

The signal transduction pathway involved in the activation of pyruvate dehydrogenase (PDH) by insulin is still unknown. In this study, we have examined the possible involvement of protein kinase C (PKC) in the process. In addressing this question, we examined (1) the insulin-like effects of the PKC activator 4 beta-phorbol 12 beta-myristate 13 alpha-acetate (PMA) on the PDH complex, (2) the effects of various PKC inhibitors on the PDH activation by insulin, and (3) the response of PKC-depleted cells to insulin. We used as an experimental model Zajdela hepatoma cultured (ZHC) cells, which have been demonstrated to be responsive to physiological doses of insulin. Half-maximal and maximal stimulations of the PDH complex by insulin were observed at 0.05 and 5 nmol/L, respectively. Stimulation of PDH activity by insulin (5 nmol/L) occurred within 5 minutes of incubation and was maximal (+70%) at 7.5 minutes. In the presence of PMA (162 nmol/L), enzyme activity increased within 30 seconds, was maximal (+90%) at 5 minutes, and was no longer detectable after 10 minutes. Total PDH activity was unchanged by insulin or PMA treatment. The effects of PMA and insulin on basal PDH activity were not additive. Moreover, various inhibitors of PKC--staurosporine, sphingosine, acridine orange--completely blocked the stimulation of PDH activity induced by insulin or PMA. A 17-hour treatment of ZHC cells with 500 nmol/L PMA efficiently downregulated PKC, as attested by the marked decrease in the enzyme activity and the loss of phorbol 12,13-dibutyrate binding to intact cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1994

Leigh syndrome: pyruvate dehydrogenase defect. A case with peripheral neuropathy.

Pyruvate dehydrogenase deficiency is one of the most common causes of encephalopathy associated with lactic acidosis and is known to account for congenital lactic acidosis, recurrent ataxia, and infantile Leigh syndrome. Hitherto, however, peripheral neuropathy has not been regarded as a presenting symptom of pyruvate dehydrogenase deficiency. Here, we report on a boy who presented peripheral neuropathy with severe limb hypotonia, absent deep-tendon reflexes, and reduced motor nerve conduction velocities at 8 months of age. Persistent hyperpyruvicemia with normal lactate/pyruvate molar ratios in plasma were highly suggestive of a pyruvate dehydrogenase deficiency, and the determination of pyruvate dehydrogenase activity in circulating lymphocytes led to the diagnosis of pyruvate decarboxylase (PDH-E1) deficiency in the proband. Based on this observation, we suggest that pyruvate dehydrogenase deficiency should be considered in the diagnosis of peripheral neuropathy in infancy, especially when associated with persistent hyperpyruvicemia, normal lactate/pyruvate molar ratios in plasma, and recurrent episodes of drowsiness and hypotonia of unknown origin.

Brain↗
PubMed1994

Aberrant splicing of exon 6 in the pyruvate dehydrogenase-E1 alpha mRNA linked to a silent mutation in a large family with Leigh's encephalomyelopathy.

Pyruvate dehydrogenase (PDH)-E1 alpha deficiency has recently been studied at the molecular-genetic level. The gene is situated on the X chromosome. We report on an unusual mutation in a familial E1 alpha deficiency. In fibroblasts, PDH deficiency was diagnosed in a young infant presenting with Leigh's encephalomyelopathy and in a maternal nephew with episodes of "malaises." In the two affected children as well as their mothers we found a silent mutation in exon 6 of the PDH-E1 alpha and an aberrant splicing of exon 6 in some of the cDNA clones. This case emphasizes the need for both genomic and cDNA analysis in cases where a PDH-E1 alpha deficiency is strongly suspected.

Base Sequence↗
PubMed1994

Nonparallel changes of growth hormone (GH) and insulin-like growth factor-I, insulin-like growth factor binding protein-3, and GH-binding protein, after craniospinal irradiation and chemotherapy.

We studied the GH-insulin-like growth factor-I (IGF-I) axis serially over 24-36 months in six patients with medulloblastoma who underwent surgical removal of the tumor followed by craniospinal irradiation therapy for 6 weeks and then chemotherapy for 42 weeks. Eighteen and 24 months after beginning irradiation there was a decline in the peak GH secretory response to acute stimulation with arginine/insulin hypoglycemia. Six months after irradiation and during chemotherapy there was a transient decline in IGF-I, IGF binding protein-3 (IGFBP-3), and GH-BP values (respective mean values of 56.1 +/- 9.0 ng/mL, 1.1 +/- 0.2 microgram/mL, and 7.6 +/- 3.3% of radioactivity as compared to time 0 values: 13%%o/- 15 ng/mL, 2.2 +/- 0.2 micrograms/mL, and 20.0 +/- 4.0%, P < 0.001), although provoked GH secretion was normal at this time. The IGF-I, IGFBP-3, and GH-BP returned to pretreatment ranges by 12-36 months after initiation of the study. There was also a decline in body mass index and serum protein values at 6 months, suggesting suboptimal nutrition during this period. Six months after irradiation in ligand and immunoblot analysis there was a decline in IGFBP-3 and an abnormal electrophoretic mobility of IGFBP-2 that were both normalized at 36 months. In one patient we observed a high level of IGFBP-3 proteolysis at this time. This study demonstrates that before the decrease of GH secretion in patients receiving cranial irradiation there is a transient phase of GH insensitivity that may be characteristic of the acute therapeutic phase including the chemotherapy. This partial insensitivity may explain the early growth retardation observed in these patients.

Adolescent↗
PubMed1993

Defect in the lipoyl-bearing protein X subunit of the pyruvate dehydrogenase complex in two patients with encephalomyelopathy.

Among the many metabolic encephalomyelopathies caused by deficiencies in the pyruvate dehydrogenase complex (PDHC), nearly all involve its E1 subunit. We describe two new familial cases of PDHC deficiency with encephalomyelopathy, chronic lactic acidemia, and a normal E1 subunit of PDHC but deficiency in another component. Activity of PDHC was measured in cultured skin fibroblasts and skeletal muscle, and immunoblot studies were performed on mitochondrial extracts from skin fibroblasts. Spectra of muscle tissue, obtained in vivo with phosphorus 31 nuclear magnetic resonance, were recorded both at rest and with exercise. The PDHC activity was markedly reduced to 10% to 20% of normal values in both cultured skin fibroblasts and skeletal muscle. Immunoblotting of skin fibroblast mitochondrial extracts showed a specific deficiency in the protein X component of PDHC but normal E1, E2, and E3 components. Spectra obtained with 31P nuclear magnetic resonance showed alterations compatible with those found in mitochondrial myopathies. This is the second description of an encephalomyelopathy associated with a specific absence of the lipoyl-containing protein X component, which has a structural role in the formation of a functional PDHC.

Child, Preschool↗
PubMed1993

E1 pyruvate dehydrogenase deficiency in a child with motor neuropathy.

We report the case of a boy who developed a motor neuropathy during infectious episodes at 18 mo and 3 y of age. When he was 7 y old, he suffered persistent weakness and areflexia; his resting lactate and pyruvate values were 3.65 mM and 398 microM, respectively (controls: 1.1 +/- 0.3 mM and 90 +/- 22 microM), and an exercise test demonstrated a lactic acidosis (13.6 mM; controls: 6.4 +/- 1.3 mM) with a high pyruvate level (537 microM; controls: 176 +/- 15 microM) and a low lactate/pyruvate ratio (24.2; controls: 35 +/- 2). The results of polarographic studies on muscle mitochondria suggested a defect in pyruvate oxidation (pyruvate 17 ng atom O/min/mg protein; controls: 115 +/- 42), whereas glutamate, palmitoylcarnitine, and succinate were good respiratory substrates. The activity of total pyruvate dehydrogenase complex (PDHC) in muscle mitochondria and in fresh mononuclear cells was markedly decreased (9.7 and 0.054 nmol 14CO2/min/mg protein, respectively; controls: 123 +/- 4.5 and 0.733 +/- 0.03, respectively). Immunochemical analysis in muscle mitochondria demonstrated an absence of the alpha and beta E1 PDHC subunits. After 2 y of treatment with 500 mg/d thiamine, the patient was clinically improved. A genetic study of the main regions of mutations (exon 10 and 11) in the X chromosome encoding for the E1 alpha subunit of PDHC did not show any mutation. These data indicate that, although genetically different, this case enters in a very rare category of patients with PDHC deficiency without cerebral dysfunction and improved by thiamine + L-carnitine therapy.

Base Sequence↗
PubMed1992

Pyruvate dehydrogenase activity is stimulated by growth hormone (GH) in human mononuclear cells: a new tool to measure GH responsiveness in man.

Human peripheral mononuclear cells (PMC) were used to examine the effects of hGH and insulin on the activity of the pyruvate dehydrogenase (PDH) complex. Incubation of PMC with 10(-7) mol/L hGH or insulin increased basal PDH activity. Hormonal effects were maximal (50-60% above control values) at 15 min. Later on, activation progressively decreased and was no longer detectable at 30 min. Total PDH activity was unaffected by hormonal treatment. PMC were subfractionated into lymphocytes and monocytes to assess the sensitivity of each cell types to the hormones. hGH significantly increased basal PDH activity in lymphocytes and monocytes (38% and 70% above control values, respectively), whereas insulin increased basal PDH activity only in monocytes (151% above control value). PMC from healthy subjects aged 1-45 yr were incubated for 15 min with 10(-7) mol/L hGH or insulin before PDH measurement. An increase of enzyme activity higher than 20% was observed in 26 patients out of 29 with hGH, and in 15 out of 18 with insulin. In conclusion, hGH is able to stimulate PDH activity of human mononuclear cells. This hormonal effect allows rapid evaluation of the cellular responsiveness of hGH in various pathophysiologic situations.

Adolescent↗
PubMed1991

Laugier-Hunziker syndrome: a clinical, histopathologic, and ultrastructural study of four cases and review of the literature.

Four cases of Laugier-Hunziker syndrome are described. In all patients (two men and two women between 39 and 57 years of age) pigmentation of the lower lip and hard palate was found. in addition, two patients had involvement of the buccal mucosa; another patient also had pigmentation of the upper lip, the gums, the soft palate, and the fingers of both hands. Histopathologic examination demonstrated an accumulation of melanin in the basal layer keratinocytes and an increase in the number of melanophages in the papillary dermis. Ultrastructural study showed the presence of numerous mature melanosomes in the cytoplasm of the keratinocytes of the basal layer and of the melanophages in the papillary dermis. Alterations of the melanocytes were not observed.

Adult↗
PubMed1991

Characterization of a liver low Michaelis-Menten constant 3',5'-cyclic adenosine monophosphate phosphodiesterase activity sensitive to thyroid status.

These studies were undertaken to assess the subcellular distribution and some biochemical properties of the hepatic cAMP phosphodiesterase(s) whose activity is modulated by the thyroid status in the rat. Thyroidectomy led to a 2-fold increase in low Michaelis-Menten constant (Km) cAMP phosphodiesterase activity in Golgi-endosomal fractions, but little affected this activity in crude particulate fractions. On analytical sucrose density gradients, an increase in cAMP phosphodiesterase activity in particulate elements which equilibrated at densities 1.17-1.22 was also observed. Acute insulin treatment did not further increase cAMP phosphodiesterase activity in Golgi-endosomal fractions of thyroidectomized rats. Up to 75% of the cAMP phosphodiesterase activity associated with Golgi-endosomal fraction of euthyroid and hypothyroid rats was inhibited by cGMP (IC50, 10 microM and 1 microM, respectively). Activity was also potently inhibited by griseolic acid, cilostamide, and cilostazole (IC50, less than 1 microM) but was much less sensitive to R0-20-1724 (IC50, 1 mM). Treatment of Golgi-endosomal fractions by a hypotonic extract of rat liver lysosomes led to the solubilization of 50% of low Km cAMP phosphodiesterase activity. On sucrose density gradients, the solubilized activity migrated as a slightly asymmetrical peak with a sedimentation coefficient of 6 S in euthyroid rats and 6.9 S in hypothyroid rats. On nondenaturing polyacrylamide gel electrophoresis, the activity migrated as two majors peaks with Rf values of 0.23 and 0.50; only the activity associated with the fast-moving peak was increased by thyroidectomy. On diethylaminoethyl-Sephacel chromatography, four peaks of cAMP phosphodiesterase activity, two of which were cGMP-inhibitable, were resolved. Thyroidectomy increased the activity associated with one of the cGMP-inhibitable peaks (eluted at 0.7-0.9 M sodium acetate) and led to the appearance of a new peak of activity (eluted at 0.4 M), which was not sensitive to cGMP. These results show that the low Km phosphodiesterase activity associated with liver Golgi-endosomal fractions, previously shown to be increased in hyperinsulinemic rats, is also increased in hypothyroid animals. They also suggest that, based on pharmacological and physical criteria, the enzyme species affected by the thyroid status belongs to the cGMP-and cilostamide-inhibited subclass of low Km cAMP phosphodiesterases.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1989

Effects of a long-lasting hyperinsulinemia induced by insulin infusion on the subcellular distribution of liver insulin receptors in the rat.

Acute hyperinsulinemia in rats have been shown to cause enhanced endocytosis of liver insulin receptors with little or no change in the total receptor number. To determine whether a similar phenomenon occurs in long-lasting hyperinsulinemia, the subcellular distribution of liver insulin receptors has been studied in rats infused continuously with insulin (0.4 and 0.2 U/h) for 4 days. In rats in which plasma insulin concentration was maintained at 15-20 ng/ml, there was, from 3 to 24 h, a 2-fold decrease in insulin binding to plasma membranes (PM), along with 2 to 4-fold increase in insulin binding to the light (GEI), intermediate (GEi) and heavy (GEh) Golgi-endosomal fractions; concomitantly, there was a 10-fold increase in the insulin content of Golgi-endosomal fractions. After 24 h, the changes in insulin binding to PM and GEI were maintained, but the increase in both insulin binding activity and insulin content of GEi and GEh became progressively less marked, although plasma insulin concentration remained elevated. Throughout infusion, insulin binding to the total particulate fraction was unchanged. In rats, in which plasma insulin was maintained at 6-8 ng/ml, insulin binding to PM was decreased to a lesser degree and insulin binding to Golgi-endosomal fractions was unchanged (GEh) or decreased (GEI and GEi), although the insulin content of these fractions remained high. These results suggest that, while an enhanced receptor endocytosis accounts for the decrease in cell surface receptors observed at an early stage of the hyperinsulinemia, additional regulatory mechanisms are probably involved at a later stage.

Animals↗
PubMed1988

Insulin-dependent changes in subcellular distribution of liver insulin receptors in obese Zucker rats.

Acute hyperinsulinaemias induced by insulin and stimulants of insulin secretion have been shown to cause a translocation of liver insulin receptors from the cell surface to the intracellular compartment, with little or no change in total receptor number. To determine whether a similar phenomenon occurs in chronic hyperinsulinaemic states, we have carried out a longitudinal study of total, cell surface and intracellular liver insulin receptors in genetically obese Zucker rats, with spontaneously develop hyperinsulinaemia. Liver plasma membranes, Golgi-endosomal fractions, a microsomal fraction and a total particulate fraction were isolated in 2-14-week old obese (fa/fa) rats and examined for specific insulin binding relative to lean (Fa/?) age-matched animals. In 16-day old rats, which were still normoinsulinaemic, insulin binding was unchanged. Later on, as hyperinsulinaemia developed, three sequential changes in insulin binding activity were observed: first, a 25-30% increase in Golgi-endosomal fractions (20 days); then, a 50-60% decrease in Golgi-endosomal fractions (4-5 weeks); and finally, a 50% decrease in plasma membranes (11 weeks), microsomal fraction and total particulate fraction (14 weeks), accompanied by restoration in Golgi-endosomal fractions (8-11 weeks). Unlike insulin receptors, insulin extractable from Golgi-endosomal fractions at 4-5 weeks was unchanged or increased. We conclude that, although an early increase in the endocytosis of liver insulin receptors may occur in hyperinsulinaemic Zucker rats, this mechanism does not account for the later decrease in cell surface receptors observed in these animals.

Aging↗