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Biomedical subjects

S Bernasconi

Publications and source records attributed to S Bernasconi.

At least 127 records · Page 7Linked to original sources
PubMed1996

Expression of ICAM-1 and VCAM-1 in human malignant mesothelioma.

Intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) are cytokine-inducible adhesion molecules which recognize ligands that are highly expressed on leukocytes. Expression of ICAM-1 and VCAM-1 was investigated in tissue sections of 16 cases of malignant mesothelioma (seven epithelial, eight biphasic, and one sarcomatoid) using immunohistochemistry. Neoplastic cells were diffusely and intensely stained for ICAM-1 in all cases. VCAM-1 was detected in 14 of 16 cases. The percentage of VCAM-1-positive tumour cells was more than 50 per cent in eight cases and the staining was observed mainly in epithelial-like cells. VCAM-1 was rarely expressed in other malignant tumours of epithelial origin, being present in only 1 of 58 cases of carcinoma originating from different anatomical sites. At the cellular level, ICAM-1 and VCAM-1 appeared co-distributed, the staining for both being cytoplasmic with a membrane reinforcement. The regulation of VCAM-1 expression by neoplastic mesothelial cells was investigated in vitro using 14 mesothelioma cell lines. ICAM-1 was expressed by cultured cells of all mesothelioma cell lines, even in the absence of cytokines. VCAM-1 was detected in 10-50 per cent of the cells in three non-stimulated mesothelioma cell lines (mero-95, mero-96, and mero-134), and was absent or poorly expressed in the remaining 11. Exposure of a negative cell line (mero-48a) to an optimal concentration of tumour necrosis factor alpha (TNF alpha) or interleukin-13 (IL-13) for 6-18 h resulted in the induction of VCAM-1 mRNA synthesis and in VCAM-1 expression at the membrane level in 60-70 per cent of the cells. These findings are consistent with the possibility that TNF alpha, IL-13, or other activating signals are released in the tumour micro-environment and regulate the expression of VCAM-1 in malignant mesothelioma cells.

Blotting, Northern↗
PubMed1996

Selective elevation of monocyte chemotactic protein-1 in the cerebrospinal fluid of AIDS patients with cytomegalovirus encephalitis.

The CC chemokine monocyte chemotactic protein-1 (MCP-1) was markedly elevated in the cerebrospinal fluid (CSF) of human immunodeficiency virus (HIV)-infected patients with cytomegalovirus (CMV) encephalitis. The MCP-1 CSF levels in CMV encephalitis were markedly higher than those in the CSF of HIV-infected patients with or without unrelated neurologic diseases, including progressive multifocal leukoencephalopathy, cryptococcal meningitis, toxoplasmic encephalitis, and primary lymphoma. Interleukin-8, RANTES, macrophage inflammatory protein (MIP)-1 alpha, and MIP-1 beta were not substantially increased in the CSF of CMV encephalitis patients. High levels of MCP-1 may underlie monocyte recruitment and tissue damage in CMV encephalitis and may represent a rapid and useful tool in the diagnostic armamentarium for neurologic disorders associated with HIV infection.

AIDS-Related Opportunistic Infections↗
PubMed1996

Spontaneous cortisol and growth hormone secretion interactions in patients with nonclassic 21-hydroxylase deficiency (NCCAH) and control children.

Both exogenous and endogenous hypercortisolism result in reduced GH secretion and decreased somatic growth. However, little is known about the relation between endogenous cortisol and GH secretion under physiological or slightly disturbed conditions. To examine this, we measured and evaluated the pulsatility and circadian rhythmicity, and we cross-correlated the secretory patterns of cortisol and GH in six prepubertal patients with nonclassic 21-hydroxylase deficiency (NCCAH) and seven age-matched short-normal children. Cortisol and GH were secreted in a pulsatile fashion in both the NCCAH and control groups. The nocturnal peak cortisol increment and time-integrated area were lower in the NCCAH patients than in controls, whereas there was no difference in the total 24-h cortisol secretion between the two groups. The nocturnal increase of GH in NCCAH children, on the other hand, was associated with a significant augmentation of the pulse amplitude, whereas in control children there was an elevation of the baseline component. The cross-correlation analysis of the 24-h raw data showed that cortisol and GH were negatively correlated at brief lag times of 0-30 min, and positively correlated at long lag times of 12-12.5 h in both groups, with cortisol leading GH. The negative correlation might reflect either the negative effect of glucocorticoids on the adrenergic system, which stimulates GH secretion through GH-releasing hormone (GHRH) elevations and somatostatin (SRIH) decreases, or the absence of an inhibitory effect of CRH on SRIH. The positive correlation may reflect the positive effect of glucocorticoids on the GH gene. In conclusion, NCCAH children have a mild nocturnal cortisol deficiency compared with control children, as previously reported, and a distinct circadian pattern of pulsatile GH secretion. The hypothalamic-pituitary-adrenal (HPA) axis exerts both negative and positive influences on GH secretion, with mild disturbances in cortisol biosynthesis associated with slight alterations of GH secretion.

Adrenal Hyperplasia, Congenital↗
PubMed1996

Pituitary-ovarian responses to leuprolide acetate testing in patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency.

To assess whether patients with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency exhibit a steroidogenic response to GnRH agonist consistent with functional ovarian hyperandrogenism (FOH) and elucidate the relationship between adrenal and ovarian hyperandrogenism, the LH, FSH, estradiol, 17-hydroxyprogesterone (17-OHP), androstenedione, total testosterone, dehydroepiandrosterone, and 17-hydroxypregnenolone responses to a sc dose of leuprolide acetate (500 micrograms) were evaluated in 10 patients with classic CAH (mean age, 18.4 +/- 0.95 yr), 7 of whom had oligomenorrhea, pretreated with dexamethasone (2 mg/day for 5 days, including the day of the test). The results were compared with those obtained in 11 patients with FOH (mean age, 18.7 +/- 0.46 yr) and 17 normal women (mean age, 19.68 +/- 0.59 yr) not pretreated with dexamethasone. Leuprolide acetate stimulation caused a significant augmentation of plasma E2, 17-OHP, androstenedione, testosterone, and 17-hydroxypregnenolone concentrations in all CAH patients. However, in only 6 (60%) of them, all with oligomenorrhea, was the 17-OHP response (posttest minus pretest value) similar to that of FOH patients and significantly higher than that in controls. In this subset of CAH patients, LH plasma levels after stimulation were significantly higher than those of CAH subjects with 17-OHP responses in the normal range, controls, and FOH patients, whereas FSH levels were similar to those of controls. In this latter group, plasma FSH concentrations after stimulation were significantly higher than those in FOH. In conclusion, the results of the present study indicate that LH-dependent functional ovarian hyperandrogenism is frequent in patients with classic CAH. As ovarian hyperandrogenism might be partially responsible for the menstrual irregularities that are common complications in such patients, all classic CAH patients with oligomenorrhea should undergo short term stimulation with GnRH agonists to ascertain the presence of ovarian hyperandrogenism and receive appropriate treatment.

17-alpha-Hydroxypregnenolone↗
PubMed1996

Dose-dependent inhibition of growth hormone (GH)-releasing hormone-induced GH release by corticotropin-releasing hormone in prepubertal children.

Previous studies have shown that CRH is capable of inhibiting GH release in response to GHRH in adult subjects, and this effect appeared to be sex dependent and more pronounced in women than in men. To assess whether CRH has an inhibitory action on GH release in children also, the effects of graded doses of CRH on the GHRH-induced GH secretion were studied in three groups of prepubertal children. All subjects underwent a GHRH test (1 microgram/kg), followed, on separate occasions, by the combined administration of GHRH (1 microgram/kg) and CRH (1 microgram/kg, group A, n = 6; 1.5 microgram/kg, group B, n = 6; 2 microgram/kg, group C, n = 7). GH concentrations in response to the single GHRH injection were comparable in the three groups. The combined administration of GHRH and CRH resulted in serum GH concentrations similar to those obtained in the same subjects in response to GHRH alone when 1 and 1.5 microgram/kg CRH were given. In contrast, the administration of 2 microgram/kg CRH together with GHRH led to an increase in GH concentrations significantly lower than those after the GHRH injection alone (GH area under the curve, 1022.18 +/- 106.26 vs. 3109.16 +/- 794.29 microgram/Lx24 h; P < 0.05). No differences in the GH response to GHRH alone or to GHRH plus CRH were detected between male and female subjects. The results of the present study indicate that CRH is capable of inhibiting GHRH-induced GH release in children. Moreover, the inhibitory effect by CRH appears to be dose dependent and not sex related.

Adolescent↗
PubMed1996

Latent coeliac disease. Personal experience.

Latent coeliac disease (L.C.D.) is an extremely rare condition to describe. In this study we analyzed three cases of patients affected by L.C.D.: two of them suffered from insulin-dependent diabetes mellitus (IDDM) and the other one from infantile cerebral palsy and eosinophilic gastroenteritis. We confirm the existence of this form of coeliac disease (C.D.), by means of duodenal biopsy, and stress the importance of an early diagnosis in order to prevent the serious consequences caused by untreated C.D.

Adult↗
PubMed1996

[T1G3 of the bladder: our experience].

From June 1991 to June 1995 we treated 20 patients affected by T1 G3 TCC of the bladder, 18 men and 2 women, with a mean age of 65.1 years (46-71). In 11 patients the disease was monofocal, with diameter of the tumor under 3.5 cms; in 5 patients monofocal with diameter of the tumor over 3.5 cms; in 1 patient multifocal and in 3 patients complex (mono or multifocal associated with CIS). The 11 patients with monofocal disease under 3.5 cms were treated with TUR-B, the other 9 (all males) were submitted to radical cystectomy with OINB diversion as first choice treatment. The mean follow up (all patients) was 3.2 years (6 months-14 years). Out of the patients of the former group only 3 did not show any relapse, the other 8 showed multiple relapses or metachronous tumors: 5 were treated with TUR-B+BCG, 3 were cystectomized. The patients submitted to cystectomy as first choice treatment did not show any progression of the disease after a mean follow-up of 19.8 months.

Aged↗
PubMed1996

Growth hormone treatment in short normal children.

The efficacy of growth hormone (GH) therapy in short normal children (i.e. children without classical growth hormone deficiency [GHD]) is still under debate. This paper presents the preliminary data of a retrospective Italian multicenter study on children treated with GH until adult height was reached. Final adult height (FAH), however, is not significantly different from the predicted adult height (PAH) calculated at the beginning of treatment. This result is in agreement with those reported in the majority of other similar international surveys. In conclusion, GH should be administered to short normal children only within the framework of well designed prospective experimental studies, which should consider several auxological, clinical and biochemical parameters capable of influencing the therapeutic results.

Adolescent↗
PubMed1996

Final height outcome of growth hormone-deficient patients treated since less than five years of age.

Thirteen growth hormone deficient infants underwent substitutive treatment for a least 9 years, since less than 5 years of age until adulthood. They presented with average growth failure reaching 4.1 SDS and attained an adult mean height close to target height. In eight subjects final height exceeded the respective target height and only three patients failed to achieve an end height within the target range. The analysis of the factors conditioning ultimate stature pointed out that height outcome correlated negatively with chronological age at therapy initiation and positively with height at puberty onset. It is concluded that full catch-up growth to target percentile is possible in growth hormone-deficient children, provided that substitutive treatment is begun within the 5 years of life. This conclusion is substantiated for the first time by data on end stature.

Adolescent↗
PubMed1996

[100 orthotopic neobladders in men after cystectomy: a 5-year experience].

Urethral bladder substitution is traditionally suggested to good prognosis cystectomized patients. In our series this diversion was chosen for all but the salvage cystectomized men. Between the 1st of February 1991 and the 30th of April 1996, one hundred consecutive men underwent lower urinary tract reconstruction after radical cystoprostatectomy for bladder cancer. An orthotopic ileal neobladder was constructed (in 84 cases according to Kock's technique and in 16 to Studer's technique). Total early complication rate was 29% (29/100), including one perioperative death due to sepsis (mortality rate 1%). 13 patients required surgery (6 retroperitoneal hematomas, 2 wound dehiscences, 1 urinary fistula, 1 lymphocele, 1 rectal-neobladder fistula, 1 rectal-cutaneous fistula, 1 necrosis of the terminal ureter). The late complication rate was 19% (19/100); in 8 cases reparative surgery was required (1 mechanical ileus, 2 bladder neck stenoses, 3 stenoses of the ureteral anastomosis, 2 laparoceles). Four patients were lost at the follow-up; out of the 96 remaining patients only 85 were evaluable for continence: continence during the day was achieved in a period between there to six months in 78 patients (91.7%); night continence was achieved with planned awakenings in 60 patients (70.5%). Eight patients recovered potency, another 7 had successful intercourses after PGE1 intracavernous injection. Renal function based on creatinine value was mildly impaired in 5/78 evaluable patients (6.4%) (peak creatinine 2.8 mg%). In 29 patients tumour progression was observed (29%): 9 pelvic and 20 metastatic. Among the latter 2 urethral recurrences were observed (2%). Twenty-four patients died for metastatic cancer, one for primitive lung cancer, one patient for postoperative septic shock. Adjuvant chemotherapy was administered in 11 patients without complication with an indwelling catheter in the neobladder to avoid drug reabsorption. Four patients showed complete response (2 are alive after a mean of 12 months), 6 were non responders and 1 had a partial response. In our series the ileal neobladder is a feasible method of urinary diversion when urethral cancer involvement is ruled out. Early and late complications are proportionally decreasing with experience and overall continence is satisfactory. The fate of the neobladder depends on both the technique and patient's compliance. Only educated patients can cope successfully with neobladder diversion without major complications. All the patients operated for non salvage cystectomy deserve to be diverted with a continent urethral bladder substitution.

Adenocarcinoma↗
PubMed1996

[Precocious puberty].

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Antineoplastic Agents, Hormonal↗
PubMed1995

Phosphatidic acid and lysophosphatidic acid induce haptotactic migration of human monocytes.

The present study was aimed at defining the chemotactic activity of phosphatidic acid, which is rapidly produced by phagocytes in response to chemotactic agonists. Exogenously added phosphatidic acid induced human monocyte directional migration across polycarbonate filters with an efficacy (number of cell migrated) comparable to that of "classical" chemotactic factors. In lipid specificity studies, activity of phosphatidic acid decreased with increasing acyl chain length but was restored by introducing unsaturation in the acyl chain with the most active form being the natural occurring 18:0,20:4-phosphatidic acid. Lysophosphatidic acid was also active in inducing monocyte migration. No other phospholipid and lysophospholipid tested was effective in this response. Monocyte migration was regulated by a gradient of phosphatidic acid and lysophosphatidic acid bound to the polycarbonate filter, in the absence of detectable soluble chemoattractant. Migration was also observed if phospholipids were bound to fibronectin-coated polycarbonate filters. Thus, phosphatidic acid and lysophosphatidic acid, similarly to other physiological chemoattractants (e.g. C5a and interleukin-8), induce cell migration by an haptotactic mechanism. Phosphatidic acid caused a rapid increase of filamentous actin and, at higher concentrations, induced a rise of intracellular calcium concentration. Monocyte migration to phosphatidic acid and lysophosphatidic acid, but not to diacylglycerol, was inhibited in a concentration-dependent manner by Bordetella pertussis toxin, while cholera toxin was ineffective. In the chemotactic assay, phosphatidic acid and lysophosphatidic acid induced a complete homologous desensitization and only partially cross-desensitized one with each other, or with diacyl-glycerol and monocyte chemotactic protein-1. Suramine inhibited monocyte chemotaxis with a different efficiency phosphatidic acid > lysophosphatidic acid" diacyl-glycerol On the contrary, monocyte chemotactic protein-1-induced chemotaxis was not affected by the drug. Collectively, these data show that phosphatidic acid induces haptotactic migration of monocytes that is at least in part receptor-mediated. These results support a role for phosphatidic acid and lysophosphatidic acid in the regulation of leukocyte accumulation into tissues.

Actins↗
PubMed1995

Constitutive expression of GATA-1, EPOR, alpha-globin, and gamma-globin genes in myeloid clonogenic cells from juvenile chronic myelocytic leukemia.

Juvenile chronic myelocytic leukemia (JCML) is a rare disorder of early childhood. Characteristic of JCML are the progressive appearance of high levels of fetal hemoglobin (HbF), reflecting a true reversion to a fetal type of erythropoiesis, and the presence of colony-forming cells able to grow in vitro spontaneously in the absence of growth factors. To better understand the relationship between the erythroid abnormalities and the leukemic process, we analyzed the expression pattern of specific genes related to erythroid differentiation--GATA-1, EPOR, alpha-globin, beta-globin, and gamma-globin genes--in JCML peripheral blood (PB) cells and in vitro-derived colonies. Northern blot analysis of PB cells from five JCML patients indicated levels of GATA-1 transcripts much higher than those usually found in other types of leukemic cells, and S1 nuclease protection assay detected significantly increased expression of gamma-globin mRNA. Reverse transcription-polymerase chain reaction (RT-PCR) analysis of single granulocyte-macrophage colony-forming unit (CFU-GM) colonies, obtained in vitro in the absence of added growth factors from four JCML patients, detected GATA-1, EPOR, and globin (alpha and gamma) transcripts in most of the colonies tested, in contrast with control CFU-GM from normal bone marrow, which were positive only for GATA-1. Single JCML colonies were tested for the presence of two different transcripts; whereas alpha- and gamma-globin genes appeared mostly coexpressed, beta-globin mRNA was detected only in a minority of the gamma-globin-positive colonies, indicating that the leukemic pattern of hemoglobin synthesis is mainly fetal. In addition, the leukemic cells occurring during blast crisis of one of our patients displayed the typical features of a stem cell leukemia (CD34+, CD19-, CD2-, myeloperoxidase-). In this sorted CD34+ population, we detected the presence of a marker chromosome, der(12)t(3;12), previously identified in bone marrow cells at diagnosis and an expression pattern superimposable to that of the JCML colonies, consistently displaying a high gamma-globin:beta-globin mRNA ratio. The expression of erythroid markers within populations of leukemic cells, both in vivo and in vitro, supports the hypothesis that abnormal JCML erythroid cells may originate from the same mutated progenitor that sustains the growth of the leukemic cells.

Cell Differentiation↗
PubMed1995

Effects of granulocyte-monocyte colony-stimulating factor (GM-CSF) on expression of adhesion molecules and production of cytokines in blood monocytes and ovarian cancer-associated macrophages.

The present study was aimed at characterizing the effects of in vitro exposure to GM-CSF on blood monocytes and tumor-associated macrophages (TAM) in human ovarian cancer. Purified populations of TAM from ovarian cancer patients were studied in terms of expression of surface molecules, cytokine production and tumor cytotoxicity after overnight incubation with GM-CSF or IFN gamma and LPS, used as reference activators. GM-CSF augmented the surface expression of ICAM-I and CD18 in TAM and in blood monocytes. Stimulation was more prominent in monocytes than in TAM, which showed higher baseline expression of this adhesion molecule. ICAM-3 was not influenced by GM-CSF or by IFN gamma/LPS. GM-CSF-augmented ICAM-I expression was associated with higher levels of mRNA transcripts. The protein synthesis inhibitor cycloheximide super-induced basal and GM-CSF-induced ICAM-I transcripts, thus excluding a role for secondary polypeptide mediators. In the absence of stimuli, TAM produced higher levels, compared to monocytes, of IL-6 and IL-8 but not of IL-1 and TNF. GM-CSF augmented the production of IL-6 and IL-8 (but not that of IL-1 and TNF) in TAM, whereas it had little effect on blood monocyte. Tumoricidal activity was tested against two ovarian tumor cell lines (OVCAR3 and SW626). GM-CSF more prominently augmented monocyte cytotoxicity, while only 2 of 6 TAM preparations were stimulated by GM-CSF. These results suggest that GM-CSF selectively regulates the function of blood monocytes and TAM, the effect of this cytokine varying with the parameter and cell population examined. These data provide a rational and biological endpoint for further studies with GM-CSF as an activator of mononuclear phagocyte function in ovarian cancer.

Adenocarcinoma↗
PubMed1995

Frequency of Hashimoto's thyroiditis in children with type 1 diabetes mellitus.

A total of 1419 children with type 1 diabetes mellitus was investigated in order to assess the true frequency of Hashimoto's thyroiditis (HT), diagnosed by microsomal and/or thyroglobulin autoantibodies, by ultrasound and in many cases also by fine needle biopsy. According to these criteria, 55 cases (3.9%) of HT were identified, a number significantly higher (P < 0.0001) than the distribution reported in the normal paediatric population. No typical antibody pattern was seen prior to the onset of HT, nor was an antibody threshold level found which could have been diagnostic for this disease. Patients with subclinical hypothyroidism were treated with L-thyroxine and were investigated regarding the behaviour of anti-thyroid autoantibodies; however, no significant changes were seen. The data showed a high frequency of HT in diabetic children, and therefore we recommend that children with type 1 diabetes mellitus should be screened for thyroid autoantibodies and those positive should undergo periodic thyroid function testing.

Adolescent↗