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Biomedical subjects

L Cavallo

Publications and source records attributed to L Cavallo.

At least 19 recordsLinked to original sources
PubMed1997

Human p53 binds Holliday junctions strongly and facilitates their cleavage.

Holliday junctions in DNA are generated as a product of homologous recombination events. To test the hypothesis that human p53 may bind to Holliday junctions, synthetic junctions with four approximately 75-base pair (Hol75) or approximately 565-base pair (Hol565) arms were generated. As seen by electron microscopy, under conditions in which 50-61% of the Hol565 DNAs were bound by p53, 80-96% of the p53 was located specifically at the junction with, in the latter case, only 4% of the p53 visualized at the DNA ends or along the arms. Given the large number of potential binding sites, this represents very high specificity for the junctions. Gel retardation assays using the Hol75 DNA confirm these observations, and indicate that the tight junction complexes have a half-life of greater than 4 h. The binding of p53 to three-way junctions is severalfold less than to four-way junctions. Addition of p53 greatly increases the rate of resolution of the Hol75 DNA by T4 endonuclease VII and T7 endonuclease I, two enzymes known to cleave such junctions. This latter finding further confirms the interaction of p53 with Holliday junctions and suggests that p53 binding facilitates their resolution in vivo.

Binding Sites↗
PubMed1997

Biochemical selection of prepubertal patients with androgen insensitivity syndrome by sex hormone-binding globulin response to the human chorionic gonadotropin test.

Before puberty, the diagnosis of androgen insensitivity syndrome (AIS) can be difficult. We studied whether the decrease of sex hormone-binding globulin (SHBG) during the human chorionic gonadotropin (hCG) test may represent a biochemical test to select prepubertal patients with AIS. We examined prepubertal patients with AIS (n = 9, age 0.9-8.2 y), male pseudohermaphroditism not due to AIS (other-MPH) (n = 8, age 0.6-10.7 y), and control boys (n = 12, age 0.8-12.5 y). Testosterone and SHBG levels (mean +/- SD) were measured before (d 0) and after (d 5) a hCG test (1500 IU X 3 d). Testosterone levels (nmol/L) increased in all groups [AIS: from 1.5 +/- 1.2 to 22.1 +/- 11.8 (p < 0.001); other-MPH: from 0.6 +/- 0.6 to 9.2 +/- 7.4 (p < 0.02); controls: from 1.8 +/- 1.4 to 22.8 +/- 14.4 (p < 0.001)]. SHBG concentrations (nmol/L) did not change in AIS [from 66.2 +/- 15.1 to 67.5 +/- 18.6 (p = NS), delta-variation 1.7 +/- 12.7%], whereas they were significantly decreased in other-MPH [from 59.9 +/- 14.2 to 46.5 +/- 18.6 (p < 0.005), delta-variation -23.7 +/- 19.6%] and controls [from 63.0 +/- 16.9 to 33.7 +/- 14.6 (p < 0.003), delta-variation -46.9 +/- 15.2%]. Our data suggest that the SHBG changes during the hCG test can be used to assess in vivo the biologic response to androgens in prepubertal patients with ambiguous genitalia, selecting those patients in whom it is worth performing second level investigations to confirm the AIS diagnosis.

Androgens↗
PubMed1995

Auxological, clinical and neuroradiological findings in infants with early onset growth hormone deficiency.

Sixteen infants less than 2 years of age with apparently idiopathic hypopituitarism were studied. At birth, 11 of 16 patients (69%) had subnormal length associated with relative adiposity and 10 of 16 (62%) showed significant deterioration in length deficiency from birth onwards. These findings suggest that: (a) growth hormone deficiency, in a number of patients, had started well before delivery; (b) growth hormones may play a role in intrauterine growth; and (c) growth hormone may also be involved in early postnatal growth. Magnetic resonance imaging in these patients was very similar to that described in hypopituitarism of later onset. This suggests that even in the latter case, hypopituitarism may have a prenatal onset. Finally, the severity of growth failure and the coexistence of other hypopituitary symptoms at the time of diagnosis in 31% of our patients indicate that early clinical screening of hypopituitarism is possible.

Adrenal Cortex Function Tests↗
PubMed1995

Catch-up growth and height prognosis in early treated children with congenital hypopituitarism.

The aim of this retrospective study was to ascertain, whether an early growth hormone (GH) treatment can normalize height prognosis of children with congenital GH deficiency (GHD). The study covers 23 children with early onset GHD who received GH 0.1 U/kg/day from the beginning of therapy (0.4-4.9 years). This dose was corrected for weight every 3 months during the whole duration of treatment (mean 7.9 +/- 2.4 years). As a consequence of the significant growth acceleration induced by GH treatment, the patients' height deficiency at the last check had changed from a range of between -8.0 and -1.8 SDS to between +0.5 and -4.3 SDS; on the average, it was significantly less severe than before treatment. Satisfactory growth acceleration was achieved in most patients concomitantly with accelerated bone maturation, as was shown by the stable height age/bone age ratio observed during the follow-up period. The predicted ultimate height was significantly greater than the pretreatment height and it did not differ from the target height. It is concluded that catch-up growth to the target percentile in GHD patients is possible, provided that substitutive treatment is begun during the first years of life and that GH doses are adjusted periodically for weight changes.

Adolescent↗
PubMed1995

Use of combined Gn-RH agonist and hGH therapy for better attining the goals in precocious puberty treatment.

We studied 30 girls (age 6.36 +/- 1.21 years, range 4.6-8.8) affected by idiopathic precocious puberty with significant reduction of height velocity (below the 25th centile) at the end of 1 year of Gn-RHa (triptorelin intramuscular depot) treatment, to evaluate GH-IGF-I axis activity and the effects of combined Gn-RHa plus hGH therapy. After 12 months, 15 patients continued Gn-RHa and started hGH therapy for 12 months, while 15 continued treatment with Gn-RHa alone (control group). We evaluated height velocity, bone age, urinary GH, serum IGF-I and IGFBP-3 levels throughout the study; plasma GHBP levels were determined only in the first 12 months of Gn-RHa treatment. Height velocity decreased significantly during Gn-RHa treatment; it increased significantly and became higher than the control group after 12 months of Gn-RHa plus hGH treatment. During Gn-RHa therapy alone, bone age progressed less than chronological age, while in the 12 months of Gn-RHa plus hGH treatment there was a slight nonsignificant increase in bone age progression in comparison to controls. Serum IGF-I and IGFBP-3 levels decreased significantly at 12 months of Gn-RHa therapy and increased significantly after Gn-RHa plus hGH treatment. Urinary GH levels showed the same behavior. Plasma GH binding to peak II-BP, slightly lower than the prepubertal normal range before treatment, significantly increased after 12 months of Gn-RHa treatment. Therefore, in these girls, during Gn-RHa treatment alone, we have a reduction in GH-IGF-I axis activity. During Gn-RHa plus hGH therapy there was a significant increase in height velocity, in urinary GH levels, in serum IGF-I and IGFBP-3 levels. Bone age did not seem to advance faster than chronological age and this may imply a better prediction in adult height. In our opinion, only in a small percentage of patients affected by precocious puberty (with a very low predicted adult height or an important reduction of growth velocity during Gn-RHa treatment) may an association with hGH therapy be useful.

Body Height↗
PubMed1995

Bone mineral metabolism in girls with precocious puberty during gonadotrophin-releasing hormone agonist treatment.

Bone mineral metabolism and mineralization before and during treatment were studied in 10 girls aged 6.9-8.4 years affected by central precocious puberty and treated with gonadotrophin-releasing hormone agonist (GnRHa) leuprolide acetate depot, in order to understand better the consequences of oestrogen deficiency and the reduction of growth hormone (GH)-insulin-like growth factor I (IGF-I) axis activity. Before and after 12 months of therapy, the patients underwent a clonidine stimulation test and a 4-day calcitriol osteoblast stimulation test. On day 0, day 5 and at 3-month intervals thereafter, serum calcium, phosphate, alkaline phosphatase, IGF-I, IGF binding protein 3 (IGFBP-3), GH, GH binding protein and osteocalcin levels were measured; urinary calcium, phosphate and hydroxyproline levels were evaluated in fasting spot samples. Trabecular and cortical bone mass variations, measured by dual X-ray absorptiometry in the lumbar spine and by dual photon absorptiometry in the radius, respectively were evaluated before the start and after 12 months of therapy. During treatment, a decrease of serum oestradiol levels from pubertal to prepubertal levels was observed. The GH peak following clonidine diminished significantly after 1 year. Growth hormone binding protein showed a slight increase, and IGF-I and IGFBP-3 decreased, although not significantly. Osteocalcin levels decreased significantly after 9 and 12 months of treatment, but they did not change significantly after calcitriol load, either before or after GnRHa therapy. Urinary hydroxyproline decreased significantly after 12 months.(ABSTRACT TRUNCATED AT 250 WORDS)

Body Height↗
PubMed1994

Subcutaneous growth hormone administration in growth-hormone-deficient children. Continuous plus pulsatile overnight versus single daily injection: effects on growth rate velocity.

The aim of this study, performed in 10 children, was to verify if a treatment schedule, better reproducing the growth hormone (GH) physiological pattern, could achieve a greater growth response than daily s.c. administration in previously successfully treated children with an isolated idiopathic GH deficiency. A 1-month washout period was observed between the previous regimen and this study. GH (0.6 U/kg/week, the same as given previously) was administered weekly in 6 equal doses. Three children received the daily dose by a single s.c. administration (at 20.00 h) and the other 7 through a 27-gauge infusion needle inserted s.c., using a mini infusion pump permitting a constant delivery of 50% of the daily dose (20.00-08.00 h) and the administration of the other 50% through 3 equal pulses (at 20.00, 24.00, and 04.00 h). After 6 months each child changed regimen undergoing the other one with a 1-month washout interval. During the 12 months of therapy, the mean height increased from -3.2 (SE 0.45) to -2.8 (SE 0.37) SDS. When evaluating the circulating insulin-like growth factor-I pattern as well as the growth velocity and the ratio bone age increase/height age increase, no differences were noted between the two treatment regimens.

Body Height↗
PubMed1992

Diagnostic value of growth hormone-releasing hormone test in children and adolescents with idiopathic growth hormone deficiency.

Average growth hormone (GH) peaks following an i.v. growth hormone releasing hormone (GHRH) 1-29 stimulation test were significantly lower in 48 children and adolescents with GH deficiency (GHD) than in 20 age-matched controls (15.2 + 12.7 vs 37.5 + 28.1 ng/ml, 2 P less than 0.001). Twelve patients exhibited a low GH peak (less than 5 ng/ml), 27 demonstrated a normal response (greater than 10 ng/ml) and 9 showed an intermediate rise in plasma GH (5-10 ng/ml). Six of the 12 patients with low GH response to the first GHRH stimulation failed to respond to two other tests immediately before and after a 1 week priming with s.c. GHRH. These subjects with subnormal GH increase at repeat testing had total GHD (TGHD) and multiple pituitary hormone deficiency (MPHD) and had suffered from perinatal distress. On the contrary, 26 of 27 patients with normal GH response to the first test had isolated GHD and only a minority (8/27) had signs of perinatal distress. It is concluded that perinatal injuries primarily damage pituitary structures and that a pituitary defect more probably underlies more severe forms (TGHD and MPHD) of GHD.

Adolescent↗
PubMed1992

Growth hormone release during insulin tolerance, clonidine, arginine and growth hormone releasing hormone tests in short normal children and adolescents.

This study was retrospectively performed in 574 short normal children and adolescents [328 underwent insulin tolerance test (ITT), 34 clonidine test (CLON), 64 arginine test (ARG), 19 GHRH test, 52 ITT+CLON, 30 GHRH+CLON, and 47 ITT+CLON+GHRH) in order to evaluate the effect of pubertal stage on GH response to different tests and to identify the most likely mechanism of action of different stimuli. GH peak was higher during GHRH than in all other tests. Sex or start of pubertal development did not cause any GH peak difference. Low-responder (GH peak less than 10 ng/ml) percentages were similar (ITT = 13.5%, CLON = 13.4%, ARG = 13.2%, GHRH = 10.6%) also when the subjects were divided according to sex and pubertal development. ITT+CLON showed discordant results in 42/99 subjects (30/42 = 71.4% were low-responders to ITT and 12/42 = 28.6% to CLON). GH peak appeared earlier during GHRH (85% less than 45 min) and later during CLON (78%: 60-120 min) than during all other tests; GH peak during ITT showed a wide variability of time. Negative correlations were found between GH peak during GHRH and chronological age, height and bone age and during CLON and chronological age. In conclusion our data show that these tests have similar GH secretagogue reliability.

Adolescent↗
PubMed1991

Cardiac function in congenital hypothyroidism: impairment and response to L-T4 therapy.

Electrocardiograms (heart rate, QRS voltage, QRS axis in the frontal plane. Q-Tc interval) echocardiograms [left ventricular fractional shortening (LVFS); preejection period (PEP); PEP/left ventricular ejection time (PEP/LVET) ratio; end-diastolic left ventricular free wall and interventricular septum thickness; presence of pericardial effusion], and thyrotropin (TSH), thyroxine (T4), and triiodothyronine (T3) serum levels were evaluated before and 1 week, 1 and 2 months after the start of L-thyroxine (L-T4) therapy in 11 infants with congenital hypothyroidism (CH), aged 16-59 days when first seen. Before the start of therapy, infants with CH had significantly lower QRS complexes and LVFS and significantly higher values for Q-Tc, PEP, and PEP/LVET than normal infants of the same age. The QTc interval, PEP and PEP/LVET ratio of infants with CH were significantly greater before than 1 week after L-T4 therapy, and LVFS was significantly lower before than 1 month after L-T4 therapy. Four of the infants with CH had small pericardial effusions, which disappeared within the first week of therapy. QRS axis in the frontal plane, Q-Tc interval, and PEP were negatively correlated with logT4 and logT3 serum levels. PEP/LVET ratios were negatively correlated with logT4 serum values. The QRS voltage values were positively correlated with logT4 and logT3 serum values. The frontal-plane QRS axis, Q-Tc interval, and PEP/LVET ratio were positively correlated with logTSH serum levels. The QRS voltages were negatively correlated with TSH serum levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Congenital Hypothyroidism↗
PubMed1991

[Nuclear magnetic resonance and iron overload in thalassemia].

We assessed the iron load content in 36 beta-thalassemia patients by NMR correlating the results with serum ferritin levels. 22 of them were affected by beta-thalassemia major on hyper-transfusional regimen (Group A), 4 by beta-thalassemia intermedia (Group B) and 10 by beta-thalassemia major, who had been previously bone marrow transplanted (Group C). In A and C Groups the liver showed the lowest signal intensity on spin echo images (p less than 0.01; p less than 0.06, respectively). A significant correlation between the summation of signals obtained from all the examined organs and serum ferritin levels was observed by evaluating both all the patients globally (r = 0.78; p less than 0.001) and the A and C Group patients. This correlation was confirmed only in the liver both in all the patients (r = 0.77; p less than 0.001) and in A and C Group patients, when the signals obtained from each organ were evaluated.

Adolescent↗
PubMed1990

Evaluation of the growth-hormone-releasing hormone test in short normal and growth-hormone-deficient children.

Growth-hormone-releasing hormone (GHRH) tests were performed once [GHRH(1-29)NH2, 1 microgram/kg] or on 2 consecutive days [GHRH(1-44)NH2, 1 and 2 microgram/kg administered in random order] in 27 children with idiopathic, isolated growth hormone (GH)-deficiency and in 49 short normal children, all clinically prepubertal. No differences in GH release were found between the tests performed on the 1st and 2nd day or according to GHRH dose or sex, both in GH-deficient and control children. 80% of GH-deficient and 87% of control children responded (GH peak greater than 10 ng/ml) to GHRH(1-29)NH2, and 65% of GH-deficient and all control children to GHRH(1-44)NH2. No differences in GH release were found between GH-deficient GHRH responders and control children. 17% of GH-deficient and 10% of control children responded only to one of the two tests performed on 2 consecutive days; the lack of responsiveness was unrelated to GHRH dose and sequence of GHRH administration (1st or 2nd day). The GHRH test does not seem to be a reproducible test for the evaluation of GH release, nor is it useful to differentiate GH-deficient GHRH responders from short normal children.

Adolescent↗