Biomedical subjects

G Parenti

Publications and source records attributed to G Parenti.

At least 37 records · Page 2Linked to original sources

PubMed2001

Cushing's syndrome due to intermittent ectopic ACTH production showing a temporary remission during a pulmonary infection.

OBJECTIVES: In about 15-20% of patients with ACTH-dependent Cushing's syndrome the source of ACTH is outside the pituitary gland. Pulmonary tumours are the most frequent, yet not unique, source of ectopic ACTH. In some instances the localisation of an ACTH-secreting tumour may be problematic. Occult ectopic ACTH secretion indicates the occurrence of ACTH-dependent hypercortisolism with an unknown origin. Another peculiarity of Cushing's syndrome may reside in the episodic cortisol hypersecretion, which can determine a pattern characterised by hypercortisolism together with periods of remission (cyclic Cushing's syndrome). We describe a very challenging case of Cushing's syndrome due to ectopic ACTH hypersecretion, showing virtually all of the most unusual features of the disease. DESIGN: A 55-year-old woman affected by Cushing's syndrome, presenting with biochemical features of ectopic ACTH secretion, has been followed for 7 years. METHODS: Thorough basal and dynamic hormonal assessment through the past 7 years is reported. In addition, the results of extensive imaging studies are presented. RESULTS: The source of ACTH secretion has not been identified so far, and hypercortisolism has been controlled by octreotide treatment. In addition, the patient showed a cyclic pattern of hypercortisolism with a long-term remission period. A unique feature of this case is represented by the fact that we observed a temporary, yet dramatic, short-lasting remission of ACTH and cortisol hypersecretion during a pulmonary infection, which occurred while the patient was hospitalised for a periodic hormonal assessment. CONCLUSIONS: This case well represents the wide spectrum of clinical variability of Cushing's syndrome. Most interestingly, to our knowledge, this is the first report of a case of Cushing's syndrome showing a remission during an acute infection.

Adrenocorticotropic Hormone↗

PubMed2000

Increase in plasma adenosine during brain ischemia in man: a study during transient ischemic attacks, and stroke.

Adenosine is a "retaliatory metabolite" which accumulates during experimental brain ischemia and has vasodilatory and putative neuroprotective effects. The aim of this study was to assess whether human cerebral ischemia and necrosis-evaluated in the clinical models of transient ischemic attack (TIA) and stroke, respectively-acutely raise plasma adenosine levels. We studied 20 patients: 10 with TIA and 10 with stroke. In all, blood was serially sampled for assessment of plasma adenosine by an high-performance liquid chromatography method. Sampling occurred on peripheral blood during TIA and stroke upon admission, and serially thereafter every day up to 7 days and every other day up to 20 days. We found that in TIA and stroke patients, peripheral adenosine levels were increased to a similar extent upon admission (TIA = 264 +/- 53 vs. stroke = 257 +/- 60 nM, p = ns), peaked on the day 2 for TIA (300 +/- 60) and on day 3 for stroke (289 +/- 43) patients, and steadily decreased towards the normal range, reached by all TIA patients by day 5 and by stroke patients by day 15. Stroke and TIA are associated with a rapid increase in circulating plasma adenosine concentration in man, detectable in peripheral vein. The adenosine surge likely mirrors an increased production from the ischemic brain, and it lasts days (for TIA) and weeks (for stroke) after the acute event.

Adenosine↗

PubMed2000

Structure of the SLC7A7 gene and mutational analysis of patients affected by lysinuric protein intolerance.

Lysinuric protein intolerance (LPI) is a rare autosomal recessive defect of cationic amino acid transport caused by mutations in the SLC7A7 gene. We report the genomic structure of the gene and the results of the mutational analysis in Italian, Tunisian, and Japanese patients. The SLC7A7 gene consists of 10 exons; sequences of all of the exon-intron boundaries are reported here. All of the mutant alleles were characterized and eight novel mutations were detected, including two missense mutations, 242A-->C (M1L) and 1399C-->A (S386R); a nonsense mutation 967G-->A (W242X); two splice mutations IVS3 +1G-->A and IVS6 +1G-->T; a single-base insertion, 786insT; and two 4-bp deletions, 455delCTCT and 1425delTTCT. In addition, a previously reported mutation, 1625insATCA, was found in one patient. It is noteworthy that 242A-->C causes the change of Met1 to Leu, a rare mutational event previously found in a few inherited conditions. We failed to establish a genotype/phenotype correlation. In fact, both intrafamilial and interfamilial phenotypic variability were observed in homozygotes for the same mutation. The DNA-based tests are now easily accessible for molecular diagnosis, genetic counseling, and prenatal diagnosis of LPI.

Amino Acid Metabolism, Inborn Errors↗

PubMed2000

Antioxidant effect of oral dipyridamole during cerebral hypoperfusion with human carotid endarterectomy.

We sought to test the hypothesis of an antioxidant effect of dipyridamole in vivo in a model of cerebral hypoperfusion. Twenty-one patients (65+/-10 years, 11 men) undergoing carotid endarterectomy were allocated in two groups (group 1, 10 with dipyridamole, 200 mg p.o., 3-4 h before surgery; group II, 11 with placebo) in a double-blind placebo-controlled randomized design. Blood was sampled from ipsilateral jugular bulb, and plasma vitamin E content was assayed before, after 15 and 30 min of clamp, and 2 and 10 min after declamping. In 12 of them, lipoperoxides were assayed. Vitamin E plasma content decreased significantly in group II (rest, 3.71+/-0.22 mmol/mol of cholesterol, 100%) after clamp (91.5% of rest, p < 0.01) and remained unchanged during declamping (90.9% of rest, p < 0.01), but did not change in group I (rest, 3.5+/-0.44 mmol/mol of cholesterol, 100%) during clamping (99.9% of rest; p = NS) and after declamping (97.6% of rest; p = NS). Lipoperoxide concentration did not change in group I (rest, 302+/-8 a.u.; clamp, 296+/-13 a.u.; p = NS vs. rest; declamp, 304+/-8 a.u.; p = NS vs. rest), and increased significantly in group II (rest, 313+/-5 a.u.; clamp, 352+/-9 a.u.; p < 0.01 vs. rest; declamp, 343+/-6 a.u.; p < 0.05 vs. rest). Cerebral oxidative stress associated with human carotid endarterectomy can be attenuated by pretreatment with oral dipyridamole.

Aged↗

PubMed1999

Geleophysic dysplasia: 7-year follow-up study of a patient with an intermediate form.

Geleophysic dysplasia (MIM *231050) is a rare autosomal recessive disorder, characterized by short stature with short limbs, brachydactyly, joint contractures, and a good-natured facial appearance. Infiltration of liver and cardiac leaflets has been reported in some patients. Based on the clinical picture and the detection of lysosome-like inclusions in hepatocytes, tracheal mucosa, chondrocytes, and skin fibroblasts, the underlying cause of the conditions is considered to be a generalized lysosomal storage defect. We report on a new case born to consanguineous parents, first observed at age 8 months, and for whom a 7-year follow-up is available.

Abnormalities, Multiple↗

PubMed1999

Plaque surface and microembolic signals in moderate carotid stenosis.

We performed Transcranial Doppler Monitoring to detect microembolic signals (MES) in 47 patients with moderate (30%-69%) carotid stenosis proven by selective angiography. We compared the occurrence of MES with the clinical characteristics of stenosis (symptomatic or asymptomatic) and the angiographic plaque features (nonulcerated, deep ulceration, superficial ulceration, ulceration with flap, or ulceration without flap). For these cases there was no indication for endarterectomy, nevertheless we thought it would be useful to identify risk subgroups that might benefit from surgical treatment. MES were detected in 17.9% of the stenoses with a prevalence (p <. 01) in symptomatic cases (25%) compared to asymptomatic cases (14. 3%). There was a significant correlation of MES with plaque ulceration (p <.01) and particularly with ulceration without flap (p <.01). No difference between deep and superficial ulceration was observed. The availability of prospective data on this topic might be useful to select subgroups of patients with moderate carotid stenosis at risk for embolism.

Aged↗

PubMed1999

Vertebral and carotid artery dissection following chiropractic cervical manipulation.

A 50-year-old woman presented a sudden left occipital headache and a posterior circulation stroke after cervical manipulation for neck pain. Magnetic resonance imaging documented a left intracranial vertebral artery occlusive dissection associated with an ipsilateral internal carotid artery dissection with vessel stenosis in its prepetrous tract. This is the first reported case showing an associate vertebral and carotid artery dissection following cervical manipulation. Carotid dissection was asymptomatic and, therefore, its incidence may be underestimated. We emphasize that cervical manipulation should be performed only in patients without predisposing factors for artery dissection and after an appropriate diagnosis of neck pain.

Aortic Dissection↗

PubMed1999

Smith-Lemli-Opitz syndrome: evidence of T93M as a common mutation of delta7-sterol reductase in Italy and report of three novel mutations.

The Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive disorder of cholesterol biosynthesis characterised by facial dysmorphisms, mental retardation and multiple congenital anomalies. SLOS is caused by mutations of the human Delta7-sterol reductase (DHCR7) gene and, so far, 19 different mutations have been described. Among these, mutations impairing the activity of the C-terminus appear to be the most severe. Here we report the mutational analysis of the DHCR7 gene in nine Italian SLOS patients. The T93M mutation, previously reported in one patient, results the most frequent one (7/18 alleles) in our survey. Furthermore, we identified three novel mutations, two missense mutations (N407Y and E448K), and a 33 bp deletion spanning part of exon 5 and the donor splice site of intron 5.

Adolescent↗

PubMed1998

Structure and mutation analysis of the glycogen storage disease type 1b gene.

Glycogen storage disease (GSD) 1b is the deficiency of endoplasmic reticulum glucose-6-phosphate (G6P) transport. We here report the structure of the gene encoding a protein likely to be responsible for G6P transport, and its mapping to human chromosome 11q23.3. The gene is composed of nine exons spanning a genomic region of approximately 4 kb. Primers based on the genomic sequence were used in single strand conformation polymorphism (SSCP) analysis and mutations were found in six out of seven GSD 1b patients analysed.

Antiporters↗

PubMed1998

Detection of subclinical central nervous system abnormalities in two patients with mucolipidosis III by the use of motor and somatosensory evoked potentials.

We have studied motor, somatosensory, brainstem auditory and visual evoked potentials in two patients with ML III without overt neurologic symptoms. Both our patients showed abnormal central motor functions upon magnetic cortical stimulation; in addition, in one of them, we observed a decreased conduction velocity of the nervous impulse in the central tract of the upper limb somatosensory pathway, from the cervical spinal cord to sensory cortex. Our results suggest that central motor pathways are affected in both children and also that the central somatosensory system is involved in one of them. We propose that the electrophysiological techniques might be of help to detect, locate and monitor minimal neurological lesions of mild lysosomal disorders like ML III.

Central Nervous System Diseases↗

PubMed1998

Biochemical characterization of arylsulfatase E and functional analysis of mutations found in patients with X-linked chondrodysplasia punctata.

X-linked chondrodysplasia punctata (CDPX) is a congenital disorder characterized by abnormalities in cartilage and bone development. Mutations leading to amino acid substitutions were identified recently in CDPX patients, in the coding region of the arylsulfatase E (ARSE) gene, a novel member of the sulfatase gene family. Transfection of the ARSE full-length cDNA, in Cos7 cells, allowed us to establish that its protein product is a 60-kD precursor, which is subject to N-glycosylation, to give a mature 68-kD form that, unique among sulfatases, is localized to the Golgi apparatus. Five missense mutations found in CDPX patients were introduced into wild-type ARSE cDNA by site-directed mutagenesis. These mutants were transfected into Cos7 cells, and the arylsulfatase activity and biochemical properties were determined, to study the effect of these substitutions on the ARSE protein. One of the mutants behaves as the wild-type protein. All four of the other mutations resulted in a complete lack of arylsulfatase activity, although the substitutions do not appear to affect the stability and subcellular localization of the protein. The loss of activity due to these mutations confirms their involvement in the clinical phenotype and points to the importance of these residues in the correct folding of a catalytically active ARSE enzyme.

Animals↗

PubMed1998

A novel mutation of the beta-glucocerebrosidase gene associated with neurologic manifestations in three sibs.

We report on a sibship in which three members were affected by Gaucher disease. Molecular analysis of the patients showed homozygosity for a novel mutation (C5390G) of the beta-glucocerebrosidase gene, resulting in the substitution of the arginine 353 with a glycine. Western blot analysis showed a reduced amount of beta-glucocerebrosidase-related polypeptides in fibroblasts. The phenotype resulting from this mutation is characterized by visceral and skeletal manifestations. In addition, the presence of seizures and electrophysiological abnormalities only in the 3 patients and in none of the other unaffected sibs suggests that the mutation is responsible for neurologic involvement.

Adult↗

PubMed1998

Mild phenotype associated with an interstitial deletion of the long arm of chromosome 1.

We report on a 21 month old child referred to us because of facial dysmorphism and psychomotor retardation. The patient's phenotype was characterised by a wide and receding forehead, broad nasal bridge, redundant retronuchal skin, low set and poorly shaped ears, micrognathia, and small hands and feet. High resolution R and G banding karyotype analysis of peripheral blood lymphocytes showed an interstitial deletion of the long arm of chromosome 1 spanning bands q22 to q24. The cytogenetic results were confirmed by molecular analysis. The phenotype observed in our patient was relatively milder than those reported in other patients with an interstitial deletion of chromosome 1q.

Chromosome Deletion↗

PubMed1998

Ultrafast three-dimensional ultrasound: application to carotid artery imaging.

BACKGROUND AND PURPOSE: Three-dimensional (3-D) vascular ultrasound can be expected to improve qualitative evaluation of vessel pathology and to provide quantitative data on vascular morphology and function. The objective of this study was to develop an ultrafast 3-D vascular system and to validate its performance for quantitation of atherosclerosis and assessment of regional arterial distensibility. METHODS: The quantitative analysis of focal atherosclerotic lesions was validated in vitro on 27 phantoms of fibroadipous plaques of known volume (range, 100 to 600 mm3). In vivo reproducibility of plaque volume measurement was tested in 33 patients who had a total of 47 predominantly fibroadipous carotid plaques. Distensibility assessment was validated indirectly through the evaluation of age-related changes in distensibility of common carotid artery in healthy and hypertensive subjects (25 men in each group). RESULTS: The volume of plaque phantoms measured from the 3-D data set showed a very close correlation with the true volume (r=0.99; y=0.96x+12.38; P<0.01), with the mean difference between the 2 measurements being -3.12+/-15.1 mm3. High reproducibility was found for measurement of carotid plaque volume in vivo: the mean difference between measurements from 2 observers for the same data set was 0.60+/-11.2 mm3. Indexes of arterial distensibility decreased with age in healthy population, whereas this relationship was lost in hypertensive subjects. CONCLUSIONS: Ultrafast 3-D ultrasound imaging of carotid artery demonstrates good accuracy and reproducibility for atherosclerotic plaque volume measurements. The system also allows the study of age-related degenerative vascular changes.

Aged↗

PubMed1998

Pulmonary manifestations of Gaucher disease: an increased risk for L444P homozygotes?

Pulmonary disease is a complication of Gaucher disease (GD), a lysosomal disorder due to the deficiency of glucocerebrosidase. Lung involvement was investigated through chest radiography, high-resolution computed tomography of the chest, pulmonary function tests (PFT), and oxygen saturation (SaO2) at 21% FI(O2) in 13 Italian GD patients, six homoallelic for the L444P mutation (Group A), seven with various genotypes (Group B). Echocardiography and transcutaneous oxygen tension measurement at room air and after breathing 100% oxygen were performed to exclude pulmonary hypertension and/or intrapulmonary shunts. A score index (SI) including lung involvement evaluated the severity of GD. In three Group A patients with respiratory symptoms and in an asymptomatic male interstitial involvement was demonstrated; one child died of aspiration pneumonia. Group B patients had no signs of lung damage; PFT were normal in all cases but one. SaO2 was normal in both groups. Pulmonary vascular disease was ruled out in three cases with respiratory symptoms. In Groups A and B the median SI were 22 and 13, respectively (p < 0.01). L444P homozygotes appear at major risk for developing pulmonary disease, even at earlier ages. A comprehensive evaluation of lung involvement is recommended primarily in these subjects.

Adolescent↗

PubMed1997

X-linked recessive chondrodysplasia punctata due to a new point mutation of the ARSE gene.

Chondrodysplasia punctata (CP) is a heterogeneous group of bone dysplasias that are characterized by abnormal calcium deposition in areas of enchondral bone formation. The existence of an X-linked recessive form of chondrodysplasia punctata (CDPX) has been recognized in patients who are nullisomic for the Xp22.3 region, presenting with complex phenotypes. The gene of CDPX has been identified recently, and five point mutations of the gene, named ARSE, have been described. Here, we report on the clinical and molecular characterization of a patient with CDPX. The patient presented at birth with cranial and facial anomalies and short stature; an x-ray skeletal survey showed punctate calcifications and striking hand and foot abnormalities. Single strand conformation polymorphism (SSCP) and sequence analysis of the patient's DNA allowed the identification of a new mutation of the ARSE gene; this mutation causes an amino acid substitution from cysteine to tyrosine at position 492 of the ARSE predicted protein product. The clinical description of patients with CDPX due to known mutation of the ARSE is of interest for the precise delineation of the clinical spectrum of the disease.

Arylsulfatases↗

PubMed1997

The sulfatase gene family.

During the past few years, molecular analyses have provided important insights into the biochemistry and genetics of the sulfatase family of enzymes, identifying the molecular bases of inherited diseases caused by sulfatase deficiencies. New members of the sulfatase gene family have been identified in man and other species using a genomic approach. These include the gene encoding arylsulfatase E, which is involved in X-linked recessive chondrodysplasia punctata, a disorder of cartilage and bone development. Another important breakthrough has been the discovery of the biochemical basis of multiple sulfatase deficiency, an autosomal recessive disorder characterized by a severe of all sulfatase activities. These discoveries, together with the resolution of the crystallographic structure of sulfatases, have improved our understanding of the function and evolution of this fascinating family of enzymes.

Amino Acid Sequence↗

PubMed1997

Phenylketonuria in Italy: distinct distribution pattern of three mutations of the phenylalanine hydroxylase gene.

Phenylketonuria (PKU) is an autosomal recessive disease caused by the deficiency of a liver-specific enzyme, phenylalanine hydroxylase (PAH). The pattern of PAH mutations in Mediterranean populations appears to be different from that observed in northern Europe and Asia. Our aim was to study the molecular basis of PKU in Campania and Calabria, two regions of southern Italy. We studied 99 unrelated alleles, detecting 75.8% of the mutations. Our results show that 57% of all the PKU alleles are caused by three different mutations: IVS10nt-546, R261Q and L48S, which display significant differences in their relative distribution across Italy. A novel mutation, a G-to-T transversion at the codon 257 (G257C), was also identified. This mutation results in a Gly-to-Cys change in the catalytic domain of the protein.

Adolescent↗