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Biomedical subjects

S Bernasconi

Publications and source records attributed to S Bernasconi.

At least 145 records · Page 8Linked to original sources
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

Frequency, clinical and laboratory features of thyroiditis in girls with Turner's syndrome. The Italian Study Group for Turner's Syndrome.

A total of 478 patients, mean age 15.5 (3.6-25.3) years, suffering from Turner's syndrome, were studied in order to determine the frequency of autoimmune thyroiditis, which is defined as the presence of antithyroid antibodies (AT-Ab) and typical ultrasound findings. We found 106 (22.2%) patients positive for AT-Ab and of those 49 (10%) also had positive ultrasound findings, and were therefore considered to be affected by thyroiditis. This frequency is significantly higher (p < 0.001) than that seen in the normal population. Goitre was detected on clinical examination in only 16 (33%) and by ultrasound in 19 (39%) patients. Hormonal evaluation showed that 17 patients were euthyroid, 27 had compensated hypothyroidism, 2 were hypothyroid and 3 were in a hyperthyroid phase. Clinical signs or symptoms of hypothyroidism were absent in all hypothyroid patients. In patients with thyroiditis, neither a higher frequency of malformations and autoimmune diseases nor a correlation with karyotype, oestrogens or growth hormone therapy was found.

Adolescent↗
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

The detection and localization of monocyte chemoattractant protein-1 (MCP-1) in human ovarian cancer.

Chemokines may control the macrophage infiltrate found in many solid tumors. In human ovarian cancer, in situ hybridization detected mRNA for the macrophage chemokine monocyte chemoattractant protein-1 (MCP-1) in 16/17 serous carcinomas, 4/4 mucinous carcinomas, 2/2 endometrioid carcinomas, and 1/3 borderline tumors. In serous tumors, mRNA expression mainly localized to the epithelial areas, as did immunoreactive MCP-1 protein. In the other tumors, both stromal and epithelial expression were seen. All tumors contained variable numbers of cells positive for the macrophage marker CD68. MCP-1 mRNA was also detected in the stroma of 5/5 normal ovaries. RT-PCR demonstrated mRNA for MCP-1 in 7/7 serous carcinomas and 6/6 ovarian cancer cell lines. MCP-1 protein was detected by ELISA in ascites from patients with ovarian cancer (mean 4.28 ng/ml) and was produced primarily by the cancer cells. Human MCP-1 protein was also detected in culture supernatants from cell lines and in ascites from human ovarian tumor xenografts which induce a peritoneal monocytosis in nude mice. We conclude that the macrophage chemoattractant MCP-1 is produced by epithelial ovarian cancer and that the tumor cells themselves are probably a major source. MCP-1 may contribute to the accumulation of tumor-associated macrophages, which may subsequently influence tumor behavior.

Adenocarcinoma↗
PubMed1995

Changes in dopaminergic control of circulating melanocyte-stimulating hormone-related peptides at puberty.

Desacetyl alpha-melanocyte-stimulating hormone (MSH) (ACTH 1-13) is the main form of immunoreactive alpha-MSH circulating in human plasma. This study evaluates the possibility that a dopaminergic inhibitory mechanism could be operative during human development. Thus, alpha-MSH and ACTH 1-13 plasma levels were measured after dopaminergic blockade (domperidone (0.3 mg/kg body weight, maximum 10 mg, p.o.) in 13 prepubertal (aged 4.5-12.3 y) and 12 pubertal (aged 10.2-16.9 y) children. Both peptides were measured by RIA after plasma extraction on Sep-pak C-18 cartridges and reverse phase HPLC. The chromatographic profile of alpha-MSH immunoreactivity falls into two main peaks, corresponding to the retention time of alpha-MSH and ACTH 1-13. Moreover, in prepubertal children domperidone induced a significant increase of alpha-MSH from 1.7 (median) to 5.0 pmol/L, whereas no changes in alpha-MSH plasma levels were found in pubertal subjects (from 5.0 to 4.1 pmol/L). Similarly, ACTH 1-13 plasma levels significantly increased from 3.0 to 19.8 pmol/L in prepubertal children remaining stable in pubertal ones (from 7.8 to 4.6 pmol/L). Moreover, a significant negative correlation was found between basal DHEA-S levels and the plasma alpha-MSH increase after domperidone. These data demonstrate that: 1) ACTH 1-13 is the main form of immunoreactive alpha-MSH in prepubertal life and 2) the dopaminergic inhibition of both ACTH 1-13 and alpha-MSH plasma levels is apparent only in prepubertal subjects.

Adolescent↗
PubMed1995

Growth hormone response to growth hormone-releasing hormone (GHRH), insulin, clonidine and arginine after GHRH pretreatment in obese children: evidence of somatostatin increase?

To clarify the possible neuroendocrine mechanisms underlying the impairment in growth hormone (GH) secretion present in obesity, the GH response to GH-releasing hormone (GHRH, N = 6), insulin hypoglycemia (N = 6), clonidine (N = 7) and arginine (N = 8) after GHRH pretreatment (1 microgram/kg iv 2 h before the tests) was evaluated in 27 obese peripubertal children and in a group of normal-weight short-normal children (N = 26). Growth hormone-releasing hormone pretreatment and all further stimuli elicited a statistically significant GH response in both obese and short-normal children; in the latter group arginine did not induce a significant GH response. No differences were found among the GH responses after the second stimuli in obese children, while in short-normal children the arginine peak and area values were lower than after GHRH and clonidine. Comparison between the two groups showed similar baseline but higher stimulated GH levels in normal-weight children after all tests except arginine, after which no difference was present. In conclusion, the neuroregulation of GH release seems to be similar qualitatively in normal-weight and obese youngsters; the different behavior observed after arginine, which is supposed to act through somatostatin inhibition, might be due to a chronic increase in somatostatinergic tone responsible for the lower stimulated GH levels in obesity.

Adolescent↗
PubMed1995

Growth hormone-releasing effect of oral growth hormone-releasing peptide 6 (GHRP-6) administration in children with short stature.

Growth hormone-releasing peptide 6 (GHRP-6) is a synthetic hexapeptide with a potent GH-releasing activity after intravenous, subcutaneous, intranasal and oral administration in man. Previous data showed its activity also in some patients with GH deficiency. The aim of our study was to verify the GH-releasing activity of oral GHRP-6 administration on GH secretion in children with normal short stature. The effect of oral GHRP-6 (300 micrograms/kg) was compared with that of the maximally effective dose of intravenous GH-releasing hormone (GHRH-29, 1 microgram/kg). As the GHRH-induced GH rise in children is potentiated by arginine (ARG), even when administered by oral route at low dose (4 g), we studied also the interaction of oral GHRP-6 and ARG administration. We studied 13 children (nine boys and four girls aged 6.2-10.5 years, pubertal stage I) with normal short stature (height less than -2 SD score; height velocity more than -2 SD score; normal bone age; insulin-like growth factor I > 70 micrograms/l). In a first group of children (N = 7), oral GHRP-6 administration induced a GH response (mean +/- SEM; peak at 60 min vs baseline: 18.8 +/- 3.0 vs 1.1 +/- 0.3 micrograms/l, p < 0.0006; area under curve: 1527.3 +/- 263.9 micrograms l-1 h-1) which was similar to that elicited by GHRH (peak at 45 min vs baseline: 20.8 +/- 4.5 vs 2.2 +/- 0.9 micrograms/l, p < 0.007; area under curve: 1429.4 +/- 248.2 micrograms l-1 h-1).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1995

[Physiopathology of BPH obstruction].

The underlying BPH related mechanisms of outlet obstruction are outlined (modification of the shape of the bladder neck, failure of funnel formation, geometric variations of the urethra, alpha 1 adrenoceptors mediated sympathetic hyperactivity at the level of the lower genito-urinary tract). Bladder voiding dysfunction in response to prostate obstruction is also discussed and correlated to ultrastructural patterns and clinical symptoms. Finally, a pathogenetic mechanism for detrusor overactivity in obstructed bladder is suggested.

Humans↗
PubMed1995

[Alpha blockers, TUS-P and TUR-P in the treatment of benign prostatic hypertrophy. A comparison using multivariate statistical analysis].

To evaluate the effectiveness of Alpha-blockers, TUI-P and TUR-P in the treatment of obstruction due to BPH, 50 patients, never before treated, were considered. Fifteen were treated with alfuzosin chlorhydrate 7.5 mg/day for four months, 15 were submitted to TUI-P and 20 to TUR-P. In all patients linear purr was carried out before treatment and was repeated from 60 to 90 days after intervention in surgical patients and during the fourth month of treatment in patients treated with alfuzosin. The data obtained were analyzed with the T-test both for dependent and independent samples. The results show that Alpha-blocker contain an increase in maximal flow, without decreasing bladder voiding pressures. On the contrary TUI-P and TUR-P, besides the increase in maximal flow obtain a significant reduction of bladder pressures. The conclusions are the following: maximal flow alone is not a sufficient parameter to evaluate the work of the bladder, the entity of the obstruction and the effectiveness of the therapy. The treatment with Alpha-blockers is unable to reduce the obstruction due to BPH. TUI-P and TUR-P realize an effective deobstruction. Under the same deobstructing effect TUR-P assures a better voiding performance by obtaining higher flow values.

Adrenergic alpha-Antagonists↗
PubMed1995

Monocyte chemoattractant protein-1 is excreted in excessive amounts in the urine of patients with lupus nephritis.

BACKGROUND: In patients with lupus nephritis, mononuclear inflammatory cells infiltrate the renal interstitium and glomeruli, and the degree of leukocyte infiltration correlates with the severity of the renal dysfunction. The precise mediator signaling inflammatory cells to migrate into the kidney is not known. Recent findings that monocyte chemoattractant protein-1 (MCP-1), a chemotactic cytokine with a high degree of specificity for lymphocytes and monocytes, is overexpressed in glomeruli from rats with immunecomplex glomerulonephritis prompted us to explore the possibility that MCP-1 could be implicated in the renal inflammatory response of lupus erythematosus. EXPERIMENTAL DESIGN: Serum and urine levels of MCP-1 were evaluated in 10 patients with active lupus nephritis. Patients were studied at admission, before therapy, and at various time points after the first administration of high dose methylprednisolone. There was an additional observation of the four patients who underwent remission of clinical signs of the disease after chronic steroid treatment. Three additional groups, one (n = 9) of patients with inactive lupus nephritis, one (n = 9) of patients with nonlupus glomerulonephritis and high degree proteinuria, and one (n = 10) of healthy subjects, were also studied. RESULTS: In patients with active lupus nephritis, urinary MCP-1 was significantly higher than in lupus patients studied in the inactive phase of the disease or in healthy volunteers. High doses of i.v. methylprednisolone significantly lowered urinary MCP-1 in patients with active lupus nephritis. In patients undergoing remission of lupus nephritis after chronic steroid treatment, urinary MCP-1 did not correlate with either serum MCP-1 levels or proteinuria. Unlike in lupus, in patients with nonlupus forms of glomerulonephritis, urinary MCP-1 was comparable to controls. CONCLUSIONS: Altogether, the present data suggest a role for MCP-1 in mononuclear cell migration into the kidney in lupus nephritis.

Adult↗
PubMed1995

Molecules with neurotrophic effects on the human developing mesencephalic dopaminergic neurons.

Parkinson's disease (PD) is characterized by the degeneration of the mesencephalic dopaminergic (mesDA) neurons innervating the striatum. Neurotrophic factor(s) that prevents the degeneration and increases the functional activity of the remaining mesDA neurons are of substantial clinical interest. The origin and development of mesDA neurons were characterized in the human mesencephalon from 5.0 to 12 Postconception (PC) weeks. Tyrosine Hydroxylase (TH) immunoreactive cells were first demonstrated at 5.5 PC weeks next to the ventricular zone. In primary culture, TH immunoreactive neurons represent 3 to 5% of the total cells at days 7 in vitro and basic Fibroblast growth factor (bFGF) was demonstrated to induce a significant increase of both TH immunoreactive cell number and TH enzymatic activity. This effect was mediated by proliferating glial fibrillary acidic protein immunoreactive cells. Nerve growth factor treatment did not have any appreciable effect. The effect of bFGF on TH positive cells described in this human bioassay is only a preliminary evidence that, if confirmed by experiments in vivo, may provide a starting rationale for investigating alternative strategies in the treatment of PD.

Cell Division↗
PubMed1994

NGF-response of EGF-dependent progenitor cells obtained from human sympathetic ganglia.

Signalling molecules are thought to play a significant role in determining the fate of neural crest progenitor cells. The human sympathetic chain was identified at 6.5, 7.5, 8.2, 10.2 and 11.4 postconception (PC) weeks demonstrating low affinity nerve growth factor (NGF) receptors, and was processed for tissue culture. In the presence of epidermal growth factor (EGF), floating spheres of proliferating progenitor cells were developed in vitro. In the absence of EGF progenitor cells differentiated into tyrosine hydroxylase (TH)-immunoreactive neuronal and TH-negative flat cells. NGF treatment significantly increased neurite outgrowth and survival of TH-immunoreactive cells. The multipotent cells we isolated differ from previously reported sympathoadrenal progenitors in that they give rise to TH immunoreactive neurones precociously sensitive to NGF.

Cell Survival↗
PubMed1994

Regulation of endothelial and mesothelial cell function by interleukin-13: selective induction of vascular cell adhesion molecule-1 and amplification of interleukin-6 production.

The present study was designed to explore the interaction of interleukin-13 (IL-13) with vascular endothelial cells (EC). In vitro exposure to IL-13 of human umbilical vein EC induced surface expression of vascular cell adhesion molecule-1 (VCAM-1). At optimal concentrations (10 to 50 ng/mL) and exposure times (24 hours), IL-13 was a twofold to threefold less effective inducer of VCAM-1 than IL-1, which was used as reference EC activator. When IL-13 was combined with IL-1, an almost additive induction of VCAM-1 was observed. Induction of VCAM-1 by IL-13 was selective in that E-selectin and intercellular adhesion molecule-1 (ICAM-1) were unaffected. IL-13 caused a modest reduction of IL-1 induction of E-selectin and ICAM-1. Surface expression of VCAM-1 on IL-13-treated cells was associated with mRNA induction (as assessed by Northern analysis and reverse transcriptase-polymerase chain reaction), with predominance of transcripts encoding the 7 Ig domain form of this molecule. In agreement with previous reports, IL-13 inhibited cytokine production in human monocytes. In contrast, IL-13 was a weak inducer and an amplifier (in concert with IL-1) of IL-6 expression in EC. Mesothelial cells, which share properties with EC and regulate the traffic and function of leukocytes in serosal cavities, were stimulated to express VCAM-1 and IL-6 by IL-13. Thus, IL-13 elicits a spectrum of responses in vascular endothelium remarkably similar to that of IL-4 and IL-10. Interaction of these cytokines with vascular endothelium may play an important role in the induction and expression of Th2-dependent responses.

Base Sequence↗
PubMed1994

The A-myb gene is preferentially expressed in tonsillar CD38+, CD39-, and sIgM- B lymphocytes and in Burkitt's lymphoma cell lines.

The A-myb gene is structurally related to the c-mby proto-oncogene, a transcription factor involved in the regulation of hemopoietic proliferation and differentiation. Recent evidence has shown that A-myb also functions as a transcriptional activator. We have previously demonstrated that A-myb RNA is not expressed in most mature human leukocytes at rest or after mitogenic or functional activation. We show here, by using cell sorting, PCR, and Western analyses that A-myb is most highly expressed in the subsets of human tonsillar B lymphocytes with the phenotypes CD38+, CD39-, and SIgM-. The preferential expression of A-myb in these populations was seen at both the RNA and protein levels. CD38 was consistently best at separating high from low A-myb-expressing cells, whereas other markers (CD10, 22, 23, 77, 11a, and 49d) did not correlate with A-myb expression. The CD38+ population expressing the highest levels of A-myb was shown to contain mostly cycling cells inasmuch as more than 95% were in the late G1, S, G2, and M phases of the cell cycle. In addition, A-myb expression always correlated with the percentage of cells in S/G2/M in the populations sorted with either CD38, CD39, or sIgM. Small resting tonsillar B lymphocytes induced to proliferate in vitro by several different polyclonal B cell activators did not, however, express detectable levels of A-myb, although these cells were demonstrated to express CD38 and enter the S/G2/M phases of the cell cycle. These data suggest that A-myb is a marker of in vivo-activated but not in vitro-activated B lymphocytes. Finally, A-myb was also found to be highly expressed in five of seven Burkitt's lymphoma lines and in none of three EBV lymphoblastoid cell lines. This finding is in agreement with the phenotype of the normal B cells that express high levels of A-myb in vivo and suggests that A-myb may be specifically induced within germinal center B cells.

ADP-ribosyl Cyclase↗
PubMed1994

A novel mechanism of colon carcinoma cell adhesion to the endothelium triggered by beta 1 integrin chain.

We have found a monoclonal antibody, called BV7, that rapidly stimulated by 6-10-folds HT-29 colon carcinoma cell adhesion to resting human umbilical vein endothelial cells. This effect was directed to tumor cells and not to endothelial cells and was cell-specific. BV7 was also active on the HCCP-2998 but did not change adhesion to endothelial cells of other tumor cells (MG63 osteosarcoma, A375 melanoma, MHCC-1410 and Lovo colon carcinoma) even if, by flow cytometry, this monoclonal antibody could bind to them. Additionally, BV7 effect was substratum-specific, since it did not increase but rather blocked HT-29 adhesion to matrix proteins. Immunoprecipitation analysis and binding to specific transfectants revealed that BV7 recognizes beta 1-subunit of integrin receptors and antibody blocking experiments showed that alpha 2 beta 1 antibodies were able to counteract BV7 effect on HT-29 adhesion to endothelial cells. In contrast, antibodies directed to other integrins or endothelial adhesive receptors (E- and P-selectin, VCAM-1, ICAM-1, ICAM-2) were ineffective. Induction of HT-29 adhesion to endothelial cells by BV7 was Fc- and protein synthesis-independent but required metabolically active cells. The presence of physiological concentrations of divalent cations and of cytoskeletal integrity was not needed. Comparative studies with eight different prototypic beta 1 antibodies showed that five of them induced HT-29 adhesion to endothelial cells in a way unrelated to their ability to interfere with HT-29 adhesion to matrix proteins. Cross-blocking binding assays demonstrated that all the five antibodies recognized a topographically related epitope. Taken together these results provide evidence that beta 1 antibodies may trigger a novel pathway of HT-29 colon carcinoma adhesion to endothelial cells with different features in respect to other described mechanisms of tumor cell interaction with the endothelium.

Amino Acid Sequence↗
PubMed1994

Dynamics of 24-hour pulsatile cortisol, 17-hydroxyprogesterone, and androstenedione release in prepubertal patients with nonclassic 21-hydroxylase deficiency and normal prepubertal children.

To assess whether the quantitative and qualitative aspects of cortisol, 17-hydroxyprogesterone (17-OHP), and androstenedione (D4A) secretion in patients with nonclassic congenital adrenal hyperplasia (NCCAH) differ from those in normal children, 24-hour serum concentrations of these steroids were measured in five prepubertal patients with NCCAH and five normal prepubertal children. Adrenal steroid profiles obtained by 30-minute sampling were analyzed by the Pulsar program. In comparison to normal children, the 24-hour quantitative parameters of 17-OHP and D4A secretion were significantly greater in NCCAH patients, but serum cortisol concentrations were similar in the two groups. When daytime and nighttime hormone releases were separately analyzed, a significant nocturnal elevation of the cortisol area under the curve above zero level (AUCo) and 12-hour mean and 17-OHP AUCo, AUC above baseline, mean peak height, amplitude, area, and 12-hour mean was detected in normal subjects only. Conversely, NCCAH patients exhibited an increased frequency and number of 17-OHP secretory peaks at night together with a reduction of the interpeak interval. No significant day/night differences in D4A concentrations were detected either in normals or in the patients. In conclusion, the results of the present study indicate that patients with NCCAH have a distinct pattern of adrenal steroid secretion characterized by a high-frequency 17-OHP release accompanied by a relative nocturnal cortisol deficiency.

17-alpha-Hydroxyprogesterone↗