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R Gatti

Publications and source records attributed to R Gatti.

At least 127 records · Page 7Linked to original sources
PubMed1993

HPLC study of the impurities present in different ursodeoxycholic acid preparations: comparative evaluation of four detectors.

The use of HPLC with different detectors has been investigated for the analysis of bile acid impurities present in four different commercially available ursodeoxycholic acid preparations. The bile acids were efficiently separated by C18 reversed-phase HPLC using methanol-water (3:2, v/v) as the mobile phase. The detectors used for bile acid detection were: UV at 200 nm refractive index (RI) and an evaporative light scattering mass detector (ELSD II). A prederivatization method with the formation of a fluorescent naphthacyl ester has also been used. GC-MS analysis of Me-TMS bile acid derivatives was included as a reference method. The four ursodeoxycholic acid samples were 98-99% pure. The main impurities present in the samples were chenodeoxycholic acid and to a lesser extent lithocholic acid. Only one sample was found to be almost 100% pure using all the detectors. Significant agreement of the data was found between RI, ELSD II detectors and the fluorescent method; the UV detector was unsuitable for use in this method. The analytical performances of the four detectors for bile acid analysis are reported and discussed. When the four-detector data were compared with the GC-MS method, reasonable agreement resulted. Discordant results were found in the quantitation of trace impurities like lithocholic acid and/or other minor bile acids present in amounts less than 0.1%.

Bile Acids and Salts↗
PubMed1993

HPLC-fluorescence determination of bile acids in pharmaceuticals and bile after derivatization with 2-bromoacetyl-6-methoxynaphthalene.

2-Bromoacetyl-6-methoxynaphthalene was used as a pre-chromatographic fluorescent labelling reagent for the high-performance liquid chromatographic (HPLC) analysis of bile acids. The derivatization reaction was performed in an aqueous medium in the presence of tetrahexylammonium bromide by ultrasonication at 40 degrees C to give fluorescent esters which were separated by reversed-phase HPLC and detected fluorimetrically (lambda ex = 300 nm, lambda em = 460 nm). Applications to the determination of ursodeoxycholic acid (UDCA) and chenodeoxycholic acid (CDCA) in their pharmaceutical formulations are described. The method was also applied to the determination of free and conjugated bile acids in human bile samples.

Bile↗
PubMed1993

Collaborative study of the molecular epidemiology of Tay-Sachs disease in Europe.

Tay-Sachs disease is a lipidosis due to the deficiency of the lysosomal hexosaminidase A. In order to understand the molecular mechanisms of this enzyme deficiency we studied 42 patients of different ethnic origins diagnosed in Europe. The strategy used consists in HEXA cDNA amplification followed by allele-specific oligonucleotide analysis for the frequent mutations, and by chemical cleavage mismatch and denaturing gradient gel electrophoresis for the detection of new mutations. 90% of alleles were clarified in this way, showing a high heterogeneity of HEXA lesions in Tay-Sachs disease. 28 different mutations were found, 20 being identified for the first time in this group of patients.

Adult↗
PubMed1992

Loss of heterozygosity on chromosome 11 in sporadic gastrinomas.

Gastrinomas are pancreatic endocrine neoplasms that arise either sporadically or are inherited as part of the multiple endocrine neoplasia type I syndrome (MENI). Loss of heterozygosity (LOH) in the region flanking the MENI gene at chromosome 11q13 has been documented in a few sporadic and familial pancreatic endocrine tumors, but not previously in sporadic gastrinomas. It has therefore been suggested that gastrinomas develop by a mechanism different from other tumors associated with the MENI syndrome. We report LOH on chromosome 11 in 5 of 11 sporadic gastrinomas. Four of these tumors have LOH for markers flanking the MENI region. Molecular evaluation of segments of chromosomes 3, 13, and 17 known to contain cloned or putative tumor suppressor genes fail to show LOH except at one locus in one tumor. These data suggest that a tumor suppressor DNA segment exists at 11q13 that may be involved in the development of sporadic gastrinomas.

Blotting, Southern↗
PubMed1992

A homozygous missense arginine to histidine substitution at position 482 of the beta-galactosidase in an Italian infantile GM1-gangliosidosis patient.

We have studied, by the polymerase chain reaction, the beta-galactosidase cDNA from several Italian patients with infantile GM1-gangliosidosis. One homozygote for a previously undiscovered G > A mutation at position 1479, causing an arginine to histidine change, was detected. The same mutation, in heterozygosis, was identified in 6 unrelated patients, but not in 100 normal chromosomes.

Arginine↗
PubMed1992

The pathobiochemistry of uremia and hyperargininemia further demonstrates a metabolic relationship between urea and guanidinosuccinic acid.

To better understand the biosynthesis of guanidinosuccinic acid, we determined urea, arginine, and guanidinosuccinic acid levels in nondialyzed uremic and hyperargininemic patients. These substances were also determined during several years of therapy in one hyperarginiemic patient. Interrelationships of guanidinosuccinic acid levels with their corresponding urea and arginine levels were assessed by linear correlation studies. In uremic patients, a significant positive linear correlation (r = .821, p less than .001) was found between serum urea and guanidinosuccinic acid levels A significant positive linear correlation was also found between serum urea levels and urinary guanidinosuccinic acid levels (r = .828, P less than .001), but not between serum arginine levels and urinary guanidinosuccinic acid levels in hyperargininemic patients. In the intrahyperargininemic patient study, a similar significant positive correlation was found between serum urea levels and the corresponding urinary guanidinosuccinic acid levels (r = .866, P less than .001); the correlation between serum arginine levels and the corresponding urinary guanidinosuccinic acid levels was smaller. The presented analytical findings in uremic and hyperargininemic patients clearly demonstrate a metabolic relationship between urea and guanidinosuccinic acid.

Adult↗
PubMed1992

The iduronate sulfatase gene: isolation of a 1.2-Mb YAC contig spanning the entire gene and identification of heterogeneous deletions in patients with Hunter syndrome.

A recently isolated cDNA clone from the iduronate sulfatase (IDS) gene has been used both to seed a contig of overlapping yeast artificial chromosomes (YACs) and to investigate the molecular defect in patients with Hunter syndrome (MPS II). Six YAC clones were found to span the IDS gene, and those and 14 other YACs were assembled into a 1.2-Mb contig around the gene in Xq27-q28. The physical map of the region identifies several putative CpG islands, suggesting the presence of other genes in the vicinity. DNA from a patient with a translocation breakpoint in the gene also permitted the orientation of the contig in the chromosome. Southern analysis of DNA from 25 unrelated Italian Hunter syndrome patients revealed 4 with deletions or rearrangements in the IDS gene.

Blotting, Southern↗
PubMed1992

Hypertrophic gastropathy with transient sessile polyps.

We report an 8-year-old boy with hypertrophic gastropathy (HG) associated with duodenal Giardia lamblia infestation. The follow-up was complicated by the development of gastric polyps at the site of previous biopsies that spontaneously disappeared within 15 months. Despite the histological similarity, the different course between Ménétrier's disease (MD) in adults (chronic, with frequent development of sessile or pedunculate polyps) and HG (uncomplicated and usually spontaneously resolving) suggests a different pathogenesis. Viral (cytomegalovirus) and bacterial (Helicobacter pylori) infections have been described in association with HG and they could play an important pathogenetic role. The term HG better defines the childhood disease in which a conservative management is recommended.

Animals↗
PubMed1992

Plasma acetyl-carnitine concentrations during and after a muscular exercise test in patients with liver disease.

In many human tissues, fuel is stored for immediate use, as well as for energy exchange between different parts of the body. Fat and glycogen represent, together with proteins, the principal energy storage materials. During energy requirement, e.g. muscular exercise, glycogen as a local reserve, is used first to supply energy needs. Acetyl-carnitine, as an active molecular group, represents an intermediate substrate, usable directly in the working tissue. The present study investigates whether plasma acetyl-carnitine could be a useful biochemical measure for information on fuel exchange in the body, and whether it is a rapidly available energy source exchangeable among tissues with different metabolic functions, such as muscle and liver. The present study investigated control and hepatopathic subjects after maximal and submaximal muscular exercise. Hepatopathic patients may be a useful model, as liver carnitine metabolism is likely to be impaired. Plasma acetyl-carnitine before, during and after maximal exercise in hepatopathic subjects did not differ, while in normal subjects it increased. After submaximal exercise, acetyl-carnitine increased in patients, as well in controls. In the patients (n = 9) with liver metabolism disorders we observed that during maximal exercise plasma acetyl-carnitine varied from 3.26 +/- 2.18 mumol/l (time 0 min) to 4.30 +/- 2.02 mumol/l (time 20 min) and from 1.99 +/- 1.36 mumol/l to 4.83 +/- 2.60 mumol/l (p less than 0.05) in the controls (n = 7).(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcarnitine↗
PubMed1992

[Mucopolysaccharidoses: evaluation of the cranium by computed tomography and magnetic resonance].

Cranial CT and/or MRI examinations were performed in 8 patients affected with mucopolysaccharidosis. Two patients were affected with mucopolysaccharidosis IH,1 had mucopolysaccharidosis IS, 1 had mucopolysaccharidosis IV A and 4 presented mucopolysaccharidosis VI. CT and MRI showed white matter changes consisting of symmetric and diffuse hypodense areas on CT, large areas and multiple spots of prolonged T1 and T2 value on MRI. Reduced gray/white matter contrast was demonstrated on T2-weighted sequences. Furthermore, CT and MRI showed thickening of the dura mater at the cranio-cervical junction, which caused subarachnoid space narrowing in all patients. Spinal cord compression was detected in 4 patients. Additional findings were mild to severe hydrocephalus, skull dysplasia and odontoid dysplasia. Owing to the progressive clinical course of all mucopolysaccharidosis, the authors stress the importance of a careful study of the cranio-cervical junction in all the patients with mucopolysaccharidosis examined by CT or MRI in order to demonstrate essential thickening of the dura mater. In the patients with symptomatic cord compression, surgery should be considered.

Adolescent↗
PubMed1991

Fucosidosis revisited: a review of 77 patients.

Fucosidosis is a rare, autosomal recessive, lysosomal storage disorder caused by a severe deficiency of alpha-L-fucosidase in all tissues. We have conducted a review of fucosidosis, compiling data from published reports and an international questionnaire survey. Seventy-seven patients affected with fucosidosis of which 19 had not been reported before have been identified. A major aim of the present study was to define the natural history of fucosidosis. The clinical picture of fucosidosis consists of progressive mental (95%) and motor (87%) deterioration, coarse facies (79%), growth retardation (78%), recurrent infections (78%), dysostosis multiplex (58%), angiokeratoma corporis diffusum (52%), visceromegaly (44%), and seizures (38%). Whereas the original fucosidosis patients described by Durand et al. (J. Pediatr 75:665-674, 1969) were decerebrate and died before age 5 years, most fucosidosis patients have a slower course of degeneration. Mortality before age 5 years was observed in only 7 patients (9%), whereas 36 patients (64%) reached the second decade. We did not find evidence for the existence of clinical heterogeneity with a rapidly progressive type I and a slowly progressive type II fucosidosis as suggested in the literature. Instead, there seems to exist a wide continuous clinical spectrum. At the biochemical level no heterogeneity in residual fucosidase enzyme activity or cross-reacting immunoreactive fucosidase protein was observed. At the DNA level at least 4 different mutations must be responsible for fucosidosis. These genotypic differences however do not explain the observed phenotypic differences.

Carbohydrate Conformation↗
PubMed1991

Aldolase B mutations in Italian families affected by hereditary fructose intolerance.

Hereditary fructose intolerance (HFI) is an inborn error of metabolism caused by aldolase B deficiency. The aldolase B gene has been cloned and the following mutations causing HFI have been identified: A149P (a G----C transversion in exon 5), A174D (a C----A transversion in exon 5), L288 delta C (a base pair deletion in exon 8), and N334K (a G----C transversion in exon 9). We have investigated the occurrence of these mutations in 11 Italian patients affected by HFI using PCR and hybridisation to specific oligomers. We found that four patients were homozygous for the A149P mutation, two patients were homozygous for the A174D mutation, three patients were compound heterozygotes for both the A149P and A174D mutations, one patient was homozygous for the N334K mutation, and one patient did not show any of the reported mutations (HFI diagnosis carried out by aldolase B assay). The L288 delta C mutation has not been found in this survey.

Base Sequence↗
PubMed1991

Cherry-red spot myoclonus syndrome (type I sialidosis).

The authors report the sequence of the clinical symptoms in type I sialidosis or cherry-red spot myoclonus syndrome, derived from the cases personally observed and from the literature. They also report neuropathological and neurochemical data. A serial EEG study in a case shows the tendency to a progressive deregulation of cerebral electric activity. Therapeutic attempts to reduce myoclonus, which is one of the more disabling symptoms in this syndrome, are described.

Adolescent↗
PubMed1990

High-performance liquid chromatographic determination of aliphatic thiols with aroylacrylic acids as fluorogenic precolumn derivatization reagents.

The use of the methyl ester of 4-(6-methoxynaphthalen-2-yl)-4-oxo-2-butenoic acid as a fluorogenic labelling reagent for the high-performance liquid chromatography (HPLC) of biologically important thiols (glutathione, cysteine, acetylcysteine, homocysteine, cysteamine, sodium 2-mercaptoethanesulphonate and thiola) was investigated. The compound reacts selectively and rapidly (10 min at ambient temperature and pH 7.5) with the thiols to give fluorescent adducts that can be separated by reversed-phase HPLC and detected fluorimetrically (lambda em = 450 nm; lambda em = 310 nm). Applications to the determination of L-cysteine and mesna in pharmaceutical formulations are described.

Chromatography, High Pressure Liquid↗
PubMed1990

An atypical paediatric case of malignant atrophic papulosis (Köhlmeier-Degos disease).

A new case of malignant atrophic papulosis (Köhlmeier-Degos disease) is reported. Vascular symptoms began at 17 months of age with cerebral ischaemia and progressive involvement of fingers and toes with torpid ulcers and apical necrotic amputations. At 6 years of age he developed chronic intestinal ischaemia with malabsorption and a new cerebral attack; in spite of anti-aggregant therapy the disease progressed and he died 7 months after diagnosis from a third cerebral ictus. Since the typical skin lesions of the disease were absent, the diagnosis was made on the basis of a pathological pattern of an occluded biopsied artery. The elder brother presents clinical and instrumental vascular involvement without cutaneous lesions and could be slightly affected.

Arterial Occlusive Diseases↗
PubMed1990

A new syndrome with cerebro-oculo-skeletal-renal involvement.

We report on an infant male who presented with microcephaly of prenatal onset, schizencephaly, decorticated disturbance of the neurological function, congenital optic atrophy, abnormal eye movements and nystagmus. In addition, he had a skeletal dysplasia with predominant acromelic involvement and a renal disease characterized by both nephritic and nephrotic changes. The natural history of his condition included severe postnatal failure to thrive, lack of development of psychomotor milestones, intractable seizures, terminal renal insufficiency with early death. Such spectrum of phenotypic abnormalities has never been reported before and we suggest that it may represent a new syndromic entity. The differential diagnosis with the oculo-skeletal-renal syndromes, with the osteodysplastic primordial dwarfism of the Taybi-Linder type and with the Hutterite cerebro-osteo-nephrodysplasia, is discussed.

Abnormalities, Multiple↗
PubMed1990

Human growth hormone association and binding study in vitro: high performance size exclusion chromatography and radioimmunoassay-measured levels in plasma of normal and acromegalic subjects.

Human growth hormone (hGH), like other protein hormones, consists of several molecular forms both in the pituitary and in plasma. In recent years carrier proteins have been detected and studied for growth hormone, using different experimental approaches. In the present study we have attempted to investigate whether hGH could be separated and identified in molecular or aggregated forms using high performance size exclusion chromatography and a small plasma sample, without particular treatment, in order to investigate specific hGH-binding proteins in normal as well as in acromegalic subjects. Results showed that it was possible to observe binding or/and the formation of a complex between free hormone and other molecules that could be specific binding proteins. Equilibrium was reached in a few minutes (7-10 min) and was reversible, as observed with labelled hormone using low and high concentrations of hGH in the incubation medium. At 37 degrees C the associated form at equilibrium was 30% of the total (measured as percent of total radioactivity with labelled hormone) in a plasma medium in which the original growth hormone was absent. Acromegalic plasma demonstrated that the percent of the associated form (namely the 80-kDa form) was less than that in normal humans. This may be due to the fact that capacity binding and competition between labelled and non-labelled growth hormone were favorable to the non-labelled form, if only for the high concentrations in this type of pathology. Therefore our results seem to be in agreement with the hypothesis that acromegalic subjects do not lack this aggregation capacity.

Acromegaly↗