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F De Luca

Publications and source records attributed to F De Luca.

At least 55 records · Page 3Linked to original sources
PubMed2001

Serum anti-p53 autoantibodies in patients with type 1 diabetes.

The presence of antibodies reacting with the p53 tumor suppressor protein has been described in patients with some autoimmune disorders. In this study we looked for serum anti-p53 antibodies in 64 patients with autoimmune type 1 diabetes mellitus within 4 mo of diagnosis. The presence of anti-p53 antibodies was observed in 6/64 (9.4%) subjects with type 1 diabetes, and in 1/44 (2.3%) subjects with other organ-specific autoimmune diseases (18 primary biliary cirrhosis, 10 autoimmune hepatitis, 16 thyroid diseases), but in none of 45 control subjects. No relationship was found between antibodies directed against islet- and non-islet-specific antigens and anti-p53 antibodies. These findings support a possible role for p53 in some autoimmune disorders.

Adolescent↗
PubMed2001

Cystinuria phenotyping by oral lysine and arginine loading.

BACKGROUND: Cystinuria is an inherited disorder of cystine and dibasic amino acids transport that results in urolithiasis because of poor cystine solubility. Three cystinuria phenotypes, differentiated according to urinary amino acid excretion in obligate heterozygotes, were regarded as allelic variants of a monogenic disease. Two mutated amino acid transporter genes, however, have been recently identified as responsible for cystinuria. Mutations in the SLC3A1 gene. encoding for the heavy subunit of the transporter protein rBAT, were associated with type I cystinuria, whereas type II and III cystinuria were associated with mutations in the SLC7A9 gene, encoding for a light subunit of rBAT. Lysine and arginine metabolism have, therefore, been evaluated in cystinuria homozygotes and heterozygotes to better define the cystinuria phenotypes and their correlations with these emerging genotypes. PATIENTS AND METHODS: Lysine and arginine intestinal absorption and renal excretion were assessed by oral loading and compared to normal controls. Seven cystinuria homozygotes and 7 obligate heterozygotes belonging to the different types received alternately an oral dose of 0.5 mmol/kg body weight lysine or arginine. Plasma concentrations of lysine, arginine, ornithine (derived from rapid arginine conversion) were measured 0, 1, 2, and 3 hours after loading. Their urinary concentrations were measured in morning urine and in urine collected 0-6 hours after loading. RESULTS: Gut lysine absorption was deficient in type II and III, and normal in type I cystinuria homozygotes. Impaired arginine intestinal absorption, as well as massive lysine, arginine, and ornithine hyperexcretion were shared by all homozygotes, irrespective of the type. All heterozygotes shared normal lysine absorption, whereas arginine absorption was slightly impaired in type II and III heterozygotes, which also displayed high lysine, arginine, and ornithine urinary excretion after loading. CONCLUSIONS: Two cystinuria phenotypes, type I and non-type I, can be identified in both homozygous and heterozygous cystinuric subjects by oral loading tests with lysine and arginine. In agreement with recent molecular findings, non-type I cystinuria comprises mentioned type II and type III, which constitute allelic variants of a cystine and dibasic amino acid transport disorder distinct from type I cystinuria.

Adolescent↗
PubMed2000

Double-resonance J-edited (1)H-NMR detection of 6-(13)C-D-2-deoxyglucose uptake in glioma cells.

The C6 methylene protons were selectively detected in (1)H-NMR spectra of intact glioma cells incubated with 6-(13)C-D-2-deoxyglucose (6-(13)C-2dG), a (13)C-enriched glucose analog that is suitable for monitoring glucose utilization in brain tumors. Spectral editing via (1)H-(13)C scalar coupling was performed with twin spin-echo double resonance (T-SEDOR), a pulse sequence which combines chemical specificity and high sensitivity, requires no solvent pre-saturation, and can easily be adapted to imaging protocols. This work demonstrates the suitability of the pulse sequence for monitoring 6-(13)C-2dG uptake in living cells in vitro, in spite of line-broadening and the occurrence of other strong signals in the spectral region of interest (3.5-4.4 ppm).

Animals↗
PubMed2000

Evaluation of the morphology of the oval fossa for placement of devices.

OBJECTIVES: First, to examine the morphology of heart specimens with defects of the oval fossa so as to define the factors that facilitate appropriate selection of the size of devices used for inteventional closure. Second, to examine the relationship between morphology and transthoracic and transesophageal echocardiography. BACKGROUND: The success of transcatheter closure is influenced by the variable morphology of deficiencies with the oval fossa, and of the relationship of the fossa itself to adjacent structures. More appropriate selection could reduce the incidence of failures. METHODS: From over 100 specimens in the cardiac registry at the University of California, San Francisco, we judged 16 hearts with atrial septal defects within the oval fossa, either in isolation or associated with other cardiac malformation, to be suitable for this study. We measured the dimensions of the defect and the surrounding rims of the fossa. All values were normalized to the diameter of the aortic root. RESULTS: A fenestrated defect was present in 9 specimens (56%). The shape defect itself was oval in all specimens, with a ratio of major to minor axes of 1.70 + 0.63. The major axis took one of three main directions with respect to the vertical plane: in 11 specimens (69%o) it was at horizontal; in 3 (19%) it was at oblique at an angle of 45 degrees; and in 2 (12%) it was vertical. Discordance was noted in some hearts between the major axis of the defect and that of the oval fossa. Structures closest to the rim of the fossa were the aortic mound, the coronary sinus, and the hinge point of the aortic leaflet of the mitral valve. CONCLUSIONS: Extrapolating from these specimens permitted identification of the major and minor axes of the atrial septal defect by transthoracic and transesophageal echocardiography. Our study has identified landmarks and dimensions that may be employed to improve effectiveness of selection of patients for transcatheter closure of defects within the oval fossa.

Cadaver↗
PubMed2000

Long-term results with growth hormone therapy in idiopathic hypopituitarism.

More than 30 years after its introduction, growth hormone (GH) treatment is well established in children with GH deficiency. Nevertheless, the long-term results of this therapy, expressed as height, are generally considered unsatisfactory. We report on results obtained in a group of GH-deficient children who were treated with daily injections of recombinant GH within the first 5 years of life and who reached an adult height very close to their target height. The full catch-up growth to the target height demonstrated in these patients suggests that replacement therapy should be started early and continued until adulthood. Height at onset of puberty is an important variable which might significantly influence the adult height. The significant and prolonged influence of birth weight on growth response to GH therapy underlines the important role of fetal growth in planning early treatment of GH-deficient children.

Body Height↗
PubMed2000

Regulation of fetal rat bone growth by C-type natriuretic peptide and cGMP.

C-type natriuretic peptide (CNP) and its high affinity receptor-B are expressed in fetal bones. Here we show that CNP accelerates longitudinal growth of fetal rat metatarsal bones in organ culture by several mechanisms. First, CNP stimulates chondrocyte proliferation in the proliferative zone as assessed by [3H]thymidine incorporation. Second, CNP stimulates cell hypertrophy as assessed by quantitative histology. Third, CNP stimulates cartilage matrix production as assessed by incorporation of 35SO4 into glycosaminoglycans. Natriuretic peptide receptor-B contains an intracellular guanylyl cyclase catalytic domain. We therefore hypothesized that cyclic GMP (cGMP) would reproduce the effects of CNP on fetal bones. Consistent with this hypothesis, we found that 8-Br-cGMP, like CNP, stimulates longitudinal growth and glycosaminoglycan synthesis. However, unlike CNP, cGMP inhibits proliferation of growth plate chondrocytes and has no effect on hypertrophy. We conclude that CNP stimulates longitudinal bone growth by increasing chondrocyte proliferation, chondrocyte hypertrophy, and cartilage matrix production. cGMP, a second messenger for CNP, reproduces some but not all of the effects of CNP, suggesting that other signal transduction mechanisms may also be involved.

Animals↗
PubMed2000

Retinoic acid is a potent regulator of growth plate chondrogenesis.

Vitamin A deficiency and excess both cause abnormalities in mammalian longitudinal bone growth. Because all-trans retinoic acid (RA) is synthesized from vitamin A, we hypothesized that RA regulates growth plate chondrogenesis. Consistent with this hypothesis, a single oral dose of RA reduced the height of the rat proximal tibial growth plate. To determine whether RA acts directly on growth plate, fetal rat metatarsal bones were cultured in the presence of RA. In this system, RA inhibited longitudinal bone growth by three mechanisms: 1) decreased chondrocyte proliferation, (assessed by 3H-thymidine incorporation), particularly in the proliferative zone of the growth plate; 2) decreased matrix synthesis (assessed by 35SO4 incorporation into glycosaminoglycans); and 3) decreased cell hypertrophy (determined histologically). The growth-inhibiting effects of RA were completely reversed by a retinoic acid receptor (RAR) antagonist. In the absence of exogenous RA, this antagonist accelerated bone growth, as did an RA-specific neutralizing antibody, suggesting that endogenous RA negatively regulates growth plate chondrogenesis. We conclude that RA, acting through RARs, negatively regulates longitudinal bone growth by inhibiting growth plate chondrocyte proliferation, chondrocyte hypertrophy, and matrix synthesis.

Alkaline Phosphatase↗
PubMed2000

Etiology of central precocious puberty in males: the results of the Italian Study Group for Physiopathology of Puberty.

We reviewed the hospital records of 45 boys, followed in 13 pediatric departments throughout Italy, who had undergone computed tomography and/or magnetic resonance imaging for central precocious puberty (CPP). Twenty-seven patients (60%) had idiopathic CPP and 18 (40%) neurogenic CPP. A hamartoma of the tuber cinereum was found in six patients (33%). All patients with hypothalamic hamartoma had earlier onset of symptoms than patients with idiopathic CPP. Five patients (27%) were affected by type 1 neurofibromatosis, two had ependymoma and five patients had an intracranial anomaly. Basal LH and basal and peak LH/FSH ratio were greater, but not significantly, in boys with neurogenic CPP than in boys with idiopathic CPP. The highest LH peak levels were observed in patients with hamartoma; however, no correlation was observed between LH peak and the size of the hamartomas. In addition, bone age at diagnosis was more advanced in patients with hamartoma than in patients with other conditions. In conclusion, gonadotrophin-dependent precocious puberty may be of idiopathic origin or may occur in association with any CNS disorder. Further studies are needed in order to evaluate the effects of nutritional, environmental and psychosocial factors on the timing of sexual maturation, to explain the high incidence of idiopathic CPP in our male patients.

Brain Diseases↗
PubMed2000

When to stop GnRH analog therapy: the experience of the Italian Study Group for Physiopathology of Puberty.

Data reported in this study have been recently published elsewhere. The authors retrospectively analyzed the auxological response to GnRH agonist treatment and the final height (FH) outcome in 71 girls with idiopathic and truly precocious (onset before 8 years) central puberty (CTPP), who had been treated with the same therapy protocol (Decapeptyl Depot at the dose of 60 microg/kg i.m. every 28 days) for at least 2 years (since 7.0 +/- 1.3 yr) and followed until puberty was completed and FH was reached. During the entire treatment period we observed: A) a decrease of height standard deviation scores (SDS) (from 1.5+/-1.7 to 0.9+/-1.3 SDS, p<0.01); B) a striking deceleration of BA, revealed by the subnormal deltaBA:deltaCA ratio (0.2 +/- 0.1); C) an increase of predicted adult height (from 155.6+/-7.0 to 160.7+/-6.7 cm, p<0.0005). Treatment interruption was followed by notable catchdown growth, with FH (158.4 +/- 5.8 cm) lower (p < 0.025) with respect to that predicted at the end of therapy. However FH fell within the population norm and the target range in 87.3% and 90% of patients, respectively. The tallest FH was recorded in the patients who discontinued treatment at a BA of 12.0-12.5 years. We conclude that: 1) Most girls with idiopathic CTPP treated by GnRH agonists may achieve an adult height within the population norm and/or their target range; 2) The height gain from therapy onset until FH attainment, however, is generally rather limited (on average 2.9 cm) and only few patients are able to reach their target percentile; 3) The most favorable height prognosis with respect to target height (TH) is generally observed in the patients with the tallest H2 and the lowest BA2:CA2 ratio, due to the notable deterioration of height prognosis which frequently follows therapy interruption; 4) In order to strengthen the weak therapeutic effect of GnRH agonists in CTPP, this treatment should be discontinued at a BA of 12-12.5 years.

Body Height↗
PubMed2000

End results in central precocious puberty with GnRH analog treatment: the data of the Italian Study Group for Physiopathology of Puberty.

We report some end results with GnRH agonist (GnRHa) treatment in central precocious puberty (CPP), in terms of final height (FH), ovarian function, peak bone mass, body composition and psychological problems. The two studies reported (Study I and II) are part of the activity of the Italian Study Group for Physiopathology of Puberty. Study L Growth data were analyzed of three groups of patients: treated with i.n. spray buserelin, i.m. triptorelin and untreated. Both GnRHa administration modes were effective in arresting pubertal development and all girls had complete recovery of the reproductive axis after therapy. Treated patients showed an improvement in final height in comparison with untreated patients and compared to predicted height at the start of treatment with both agonist treatments. However, patients treated with the long-acting slow release preparation had a better improvement in adult height and reached or exceeded the genetic height potential. Study II. In a retrospective evaluation of the outcome in 71 girls with idiopathic CPP treated with triptorelin, we found that FH fell within the population norm and the target range in 87.3% and 90% of the patients respectively. The tallest FH was recorded in the patients who started therapy at less than 6 years of age and in those who discontinued treatment at a bone age of 12.0-12.5 yr. Finally, we and other groups have recently found normal values of bone mineral density in girls at the end of GnRHa treatment in the great majority of patients.

Aerosols↗
PubMed2000

Birth weight influences long-term catch-up growth and height prognosis of GH-deficient children treated before the age of 2 years.

OBJECTIVE: To investigate which pretreatment variables most significantly affect long-term growth response to GH therapy in children with apparently idiopathic GH deficiency (GHD) treated from a similar and very young age (less than 2 years), for the same period (7 years) and with the same therapeutic protocol. DESIGN AND METHODS: Twelve children with either isolated GHD or multiple pituitary hormone deficiency were treated with biosynthetic human GH (0.7IU/kg per week) and were examined every 6 months. Height measurements were performed by Harpenden stadiometers. Bone age was evaluated every 12 months. RESULTS: The onset of therapy was followed in all patients by an important height gain, which attained its zenith during the first year of treatment and became progressively less evident during the next 4 years. Cumulative height gain was 3.0+/-1.7SDS. Thanks to the therapy, at the end of the 7-year treatment period, average height in the entire series was not significantly far from mean target height (TH) (-0.7+/-1.3 vs -0. 3+/-0.4SDS) and average predicted height (PH) (-0.2+/-1.4SDS) was very close to TH. A stepwise regression analysis showed that both catch-up growth under therapy and PH at the end of the 7-year treatment period were positively influenced by birth weight (BW). CONCLUSIONS: a) Our 7-year prospective study on GHD infants treated with GH from less than 2 years of age confirmed the importance of early diagnosis and treatment of GHD in childhood. b) The influence of BW on growth response to GH therapy in GHD children persists over time, at least when treatment is begun from less than 2 years of age.

Age Factors↗
PubMed2000

[Long-term clinical assessment of single-lead VDD electric stimulation].

BACKGROUND: During the last decade single lead VDD pacing has been progressively affirmed as an electrotherapy of choice in patients with advanced atrioventricular block without alterations of the sinus function. It combines the benefits of P-synchronous ventricular pacing with an easy implant procedure when compared to the conventional DDD approach. The aim of this study was to evaluate the validity of such an approach in a large population of patients, all implanted in a single center. METHODS: From 1987 up to now, 317 patients, all affected by advanced atrioventricular block and without sinus node dysfunction, were implanted in our center with a single lead VDD pacemaker. During follow-up the persistence of a proper atrioventricular synchronization was assessed and evaluated. RESULTS: The mean follow-up was 3.9 +/- 2.7 years/patient (range 6-138 months). The 94.6% of implanted systems maintained the normal VDD pacing function. Permanent reprogramming in VVI mode was necessary in 17 patients (5.36%); in 12 (3.78%) because of chronic atrial fibrillation and in 5 (1.63%) for loss of atrial sensing. The percentage of atrial synchronization was optimal (> 98%) and acceptable (> 95%) in 81% and 19% of patients, respectively. Episodes of paroxysmal atrial fibrillation occurred in 3 patients. Neither inhibition by myopotentials nor occurrence of sinus node disease was observed during follow-up. These results are in accordance with those reported by previous studies, performed on a smaller population or on a multicenter basis, and are comparable with the results reported for conventional DDD pacemaker. CONCLUSIONS: Our results confirm the high reliability of the single lead VDD pacing system concerning the long-term persistence of a proper atrioventricular synchronization. Data showed above enforce our opinion that this pacing approach should be considered the treatment of choice in patients with advanced atrioventricular block and preserved sinus node function.

Aged↗
PubMed1999

Functional and structural analysis of cis-proline mutants of Escherichia coli aspartate aminotransferase.

To elucidate the role of the two conserved cis-proline residues of aspartate aminotransferase (AspAT), one double and two single mutants of the enzyme from Escherichia coli (EcAspAT) were prepared: P138A, P195A and P138A/P195A in which the two prolines were replaced by alanine. The crystal structures of P195A and P138A/P195A have been determined at 2.3-2.1 A resolution. The wild-type geometry, including the cis conformation of the 194-195 peptide bond is retained upon substitution of proline 195 by alanine, whereas the trans conformation is adopted at the 137-138 peptide bond. Quite surprisingly, the replacement of each of the two prolines by alanine does not significantly affect either the activity or the stability of the protein. All the three mutants follow the same pathway as the wild type for unfolding equilibrium induced by guanidine hydrochloride [Herold, M., and Kirschner, K. (1990) Biochemistry 29, 1907-1913]. The kinetics of renaturation of P195A, where the alanine retains the wild-type cis conformation, is faster than wild type, whereas renaturation of P138A, which adopts the trans conformation, is slower. We conclude that cis-prolines seem to have been retained throughout the evolution of aspartate aminotransferase to possibly play a subtle role in directing the traffic of intermediates toward the unique structure of the native state, rather than to respond to the needs for a specific catalytic or functional role.

Alanine↗
PubMed1999

The spin coherence relaxation in the rotating frame as a microscopy parameter for strongly coupled spin systems.

The transverse relaxation time in the rotating frame T2rho is proposed as an effective parameter to get specific contrast in solid state imaging. Several peculiarities make T2rho an interesting candidate to map dynamics and structure in solids: the effect of the secular spin interaction can be controlled by the experimenter and therefore the relaxation associated with the nonsecular terms, which is particularly sensitive to very slow dynamics, can be observed. In this paper we present preliminary results obtained on polymers and prove the capability of the MARF Imaging, enhanced by a filter based on rotary echo refocusing, to produce images of solids contrasted by T2rho.

Magnetic Resonance Spectroscopy↗
PubMed1999

Factors affecting diabetes mellitus onset in cystic fibrosis: evidence from a 10-year follow-up study.

This study reports the results of genotype characterization and of a 10-y prospective evaluation of clinical status, glucose tolerance and insulin secretion in 28 originally normoglycaemic patients with cystic fibrosis (CF). The aim of the study was to assess whether any genetic, clinical or metabolic parameters could identify in advance those patients at risk of developing diabetes mellitus over time. During the follow-up 42.8% of patients became diabetic. Neither gender, age nor clinical parameters were significantly different at entry in the patients who eventually developed diabetes compared with those who did not. Insulin secretion during oral glucose tolerance tests (OGTT) deteriorated over time in both groups, whereas a progressive deterioration of glucose tolerance was only evident in the patients who developed diabetes and increased baseline glucose areas were the only predictive parameter of diabetes onset. Genotype analysis revealed significant differences between patients with and without diabetes: deltaF508 homozygosis was more frequent in the first group and N1303K mutation in the second group. In conclusion, in CF: (i) increased glucose areas during OGTT and deterioration of glucose tolerance over time can predict the evolution towards diabetes; and (ii) deltaF508 homozygosis may predispose to the risk of diabetes, whilst N1303K mutation seems to play a protective role.

Adolescent↗
PubMed1999

Determinants of spatial polarity in the growth plate.

Growth of long bones occurs at the growth plate, a layer of cartilage that separates the epiphysis from the metaphysis. Growth plate exhibits spatial polarity. Proliferative chondrocytes undergo terminal differentiation when they approach the metaphyseal, but not the epiphyseal, border of the growth plate. The adjacent bone also exhibits spatial polarity. Metaphyseal, but not epiphyseal, blood vessels and bone cells invade the adjacent growth plate, remodeling it into bone. As a result, the metaphysis, but not the epiphysis, elongates over time. To determine whether cartilage polarity determines bone polarity and/or whether bone polarity determines cartilage polarity, rabbit distal ulnar growth plates were excised, inverted, and reimplanted in their original beds. Thus, cartilage polarity was inverted relative to bone polarity. Histological examination showed that the inverted cartilage polarity was maintained over time. In contrast, the polarity of the adjacent bone reversed after surgery, to match that of the cartilage. Blood vessel and bone cell invasion ceased in the metaphysis and arose in the epiphysis. Longitudinal bone growth (measured with weekly radiographs) occurred at the epiphyseal, not at the metaphyseal, surface of the growth plate. We conclude that the polarity of growth plate cartilage is determined by intrinsic factors. The cartilage polarity then determines the polarity of the adjacent bone and, consequently, the functional polarity of longitudinal bone growth.

Animals↗
PubMed1999

A limited repertoire of mutations of the luteinizing hormone (LH) receptor gene in familial and sporadic patients with male LH-independent precocious puberty.

Herein, we report mutation analysis of the LH receptor gene in 17 males with LH-independent precocious puberty, of which 8 were familial and 9 had a negative family history. A total of 7 different mutations (all previously reported) were detected in 12 patients. Among 10 European familial male-limited precocious puberty (FMPP) patients who had a LH receptor gene mutation, none had the Asp578Gly mutation, which is responsible for the vast majority of cases in the U.S. The restricted number of activating mutations of the LH receptor observed in this and other studies of FMPP strongly suggests that an activating phenotype is associated with very specific sites in the receptor protein. Clinical follow-up of the 5 patients who did not have LH receptor mutations shows that such cases most likely do not have true FMPP. LH receptor mutation analysis provides a sensitive tool for distinguishing true FMPP from other causes of early-onset LH-independent puberty in males.

Amino Acid Sequence↗