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Biomedical subjects

G Massa

Publications and source records attributed to G Massa.

At least 19 recordsLinked to original sources
PubMed2000

Modulation of fas-ligand (Fas-L) on human microglial cells: an in vitro study.

The expression of Fas-Ligand (Fas-L) on microglia could be relevant in multiple sclerosis immunopathology. The present study was performed to evaluate in vitro the expression of Fas-L in human microglial cells both unstimulated and after stimulation with IFN-gamma, beta-IFN-1b and beta-IFN-1b+IFN-gamma. Cells were stimulated for 6,12, 24 and 48 h. Surface Fas-L was evaluated by flow cytometry, total Fas-L by Western blot, whereas mRNA for Fas-L was measured by RT-PCR. We also evaluated the capacity of microglial cells to induce, in vitro, apoptosis on Fas-positive T leukemia Jurkat cells. Our results showed a constitutive expression of Fas-L on microglia. IFN-gamma downregulated the expression of the molecule, while beta-IFN-1b and beta-IFN-1b+IFN- gamma did not. The amount of surface Fas-L was related to the ability of microglial cells to induce apoptosis in Fas-positive target cells, which was partly inhibited by blockade of the Fas-Fas-L pathway.

Cells, Cultured↗
PubMed2000

Long-term immunological changes in azathioprine-treated MS patients.

The long-term immunological effects of azathioprine treatment have been investigated in 8 multiple sclerosis patients with different course of disease, chronic progressive (CP) or relapsing progressive (RP). We studied fluctuations in peripheral blood mononuclear cell subsets, IgG, IgM and soluble vascular cell adhesion molecule-1 (sVCAM-1), before and after 2 (T24) and 3 (T36) years of therapy. We observed a significant decrease in CD8+ cells over time and a trend to lower percentage of CD3-CD56+ cells at T24 and T36. CD4+CD45RA+ cells in MS patients were lower than in healthy controls before therapy and reached values similar to those of healthy controls at T24 and T36. The remaining immunological parameters did not show any significant fluctuations.

Adult↗
PubMed2000

Length velocity acceleration at 9 months of age in a representative birth cohort of Dutch infants.

According to the ICP (infancy-childhood-puberty) growth model, statural growth can be divided into three partially superimposed components assumed to represent different physiologic mechanisms. This model predicts a sudden acceleration of length velocity (LV) at the onset of the childhood component around 9 months. The existence of such an infancy-childhood growth spurt has not yet been firmly corroborated by epidemiological studies. In the present study length measurements were made at the target ages of 1, 3, 6, 9, 12, 15, 18 and 24 months in a birth cohort of 2034 infants. In order to check whether length growth showed a continuous smooth pattern, different mathematical models were fitted to the individual growth curves. The models included Count and Guo functions, 5th order polynomial and combinations of 5th order polynomial with the logarithmic term of the Count function and the square root term of the Guo function. We showed that in boys and girls there is a small but systematic lack of fit of the mathematical modeling, due to a sudden acceleration of LV around 9 months. In addition there was an increase in variation of attained length at this age. Comparison of unbalanced ANOVA models with and without addition of dummy variables for the target ages confirmed that there was an acceleration around 9 months that, if corrected for, leads to a significantly improved model fit (likelihood ratio test p < 0.0001). In absolute terms of LV, the misfit at 9 months was not greater than 0.5 cm/year on average. We conclude that the results of this study support the existence of a late infancy growth spurt. In our opinion, however, the magnitude of the phenomenon does not legitimate construction and use of discontinuous growth references such as the ICP reference.

Aging↗
PubMed1999

Immunological effects of in vivo interferon-beta1b treatment in ten patients with multiple sclerosis: a 1-year follow-up.

Ten patients with multiple sclerosis and treated with interferon-beta1b (IFN-beta1b) were followed-up for 1 year with quantitation of serum VCAM-1 and ICAM-1 levels, mean fluorescence intensity of HLA-DR, VLA-4, CD11a, and CD18 on peripheral blood monocytes and lymphocytes, and adhesion of peripheral blood monocytes and CD45+ cells on endothelial cell monolayers. Adhesion molecule expression and adhesion of peripheral blood monocytes to endothelium were also monitored in healthy controls. No differences in adhesion were detected between MS patients before treatment and healthy controls, while after 1 year a marked decrease in the number of monocytes and mononuclear cells adhering to human umbilical vein endothelial cell monolayers was observed in patients treated with IFN-beta1b. After 1 year of treatment a significant increase in HLA-DR on peripheral blood monocytes was also detected. Our findings regarding lowered adhesion add information to available evidence of the mechanisms of action of IFN-beta1b in MS.

Adjuvants, Immunologic↗
PubMed1998

Cerebrospinal fluid thrombomodulin and sVCAM-1 in different clinical stages of multiple sclerosis patients.

In order to investigate whether brain endothelial cells activation and/or damage could be selectively monitorized, soluble vascular cell adhesion molecule 1 (sVCAM-1) and thrombomodulin (TM) levels were studied in serum and cerebrospinal fluid (CSF) of 39 multiple sclerosis (MS) patients in various phases of the disease, 19 patients with other non-inflammatory neurological diseases (OND) and 15 patients with inflammatory neurological diseases (IND). No differences in sVCAM-1 CSF levels were detected, except for lower levels in IND compared to OND. Serum TM levels were lower in IND compared to progressive MS patients. Moreover, a significant decrease both in VCAM index and in TM index was detected in IND compared to all other groups. TM index was higher in MS patients in progression as compared to OND. The combined analysis of sVCAM-1 and TM might be a useful tool in monitoring brain endothelium activation or damage in different phases of MS.

Adult↗
PubMed1998

Modulation of ICAM-1, VCAM-1 and HLA-DR by cytokines and steroids on HUVECs and human brain endothelial cells.

The in vitro effects of dexamethasone (Dx) and low and high-dose 6-methylprednisolone (MP) on the expression of adhesion molecules ICAM-1,VCAM-1 and class II antigen HLA-DR on human brain endothelial cells (HBECs) was studied. HBECs were obtained from the surgical specimen of a multiple sclerosis patient undergoing brain surgery for vascular aneurysm. HBECs obtained from apparently normal brain capillaries of surgical specimens of two patients undergoing brain surgery for a meningioma and a low-grade glioma, respectively, were used as controls. The effect of steroids was studied both in the basal condition and after stimulation with proinflammatory cytokines (gamma-IFN and TNF-alpha). In order to detect possible endothelium local tissue specific differences, the experiment was repeated using human umbilical vein endothelial cells (HUVECs). Only high-dose MP was able to down-regulate TNF-alpha-induced VCAM-1 expression on endothelial cells.

Adult↗
PubMed1998

Immunocompetence of human microvascular brain endothelial cells: cytokine regulation of IL-1beta, MCP-1, IL-10, sICAM-1 and sVCAM-1.

Endothelia from the brains of four patients undergoing neurosurgery, including one multiple sclerosis (MS) patient, were studied in vitro to determine cytokine and chemokine production; the release of soluble adhesion molecules was also investigated. The same procedure was repeated on human umbilical vein endothelial cells (HUVECs) in order to detect possible district-specific differences. After isolation, the endothelium was cultured and stimulated with gamma-interferon (IFN), tumour necrosis factor alpha (TNF-alpha) and LPS. The results showed that brain endothelium, in our experimental conditions, does not produce interleukin (IL)-10 and produces lower amounts of IL-1beta and soluble intercellular adhesion molecule-(sICAM-1) than HUVECs do; no differences were detected in soluble vascular cell adhesion molecule-(sVCAM-1) production. MCP-1 mRNA was detected both without and after stimulation with TNF-alpha and gamma-IFN in HUVECs and MS human brain endothelial cells (HBECs), while in non-MS-HBECs it was found only after gamma-IFN stimulation.

Adult↗
PubMed1998

Body mass index in growth hormone deficient children before and during growth hormone treatment.

Growth hormone deficiency (GHD) is associated with truncal obesity. We aimed at identifying factors that determine the body mass index (BMI) of untreated GHD children and the changes in BMI during 2 years of GH therapy in 348 Dutch GHD children registered in the National GH Registration Database. BMI was expressed as a standard deviation score (SDS). Before GH therapy, the mean (95% CI) BMI-SDS in all GHD children (0.09 (-0.05 to 0.24) SDS) was comparable to normal children. Patients with GHD due to a cranial tumour have a higher BMI (1.03 (0.69-1.36) SDS; p < 0.0001) as well as those with multiple pituitary hormone deficiencies (0.35 (0.14-0.57) SDS; p = 0.005) and patients who are in puberty at start of GH therapy (0.60 (0.13-1.08) SDS; p = 0.036). During GH therapy BMI initially decreased to reach a nadir of -0.28 (-0.35 to -0.21) SDS at 6 months. Thereafter BMI progressively increased to -0.09 (-0.18 to -0.04) SDS after 24 months. A higher initial BMI-SDS resulted in a larger decrease in BMI-SDS. We showed that this can be sufficiently explained by a regression to the mean effect.

Age Factors↗
PubMed1998

Plasma levels of insulin-like growth factor (IGF)-I, IGF-II and IGF-binding protein-3 in the evaluation of childhood growth hormone deficiency.

BACKGROUND: Traditionally, measurement of plasma IGF-I and more recently of IGFBP-3 are used to distinguish GHD from idiopathic short stature in slowly growing children, using a single blood sample. In earlier studies it was claimed that IGFBP-3 was superior to IGF-I, but more recently doubts around this claim have arisen. The role of serum IGF-II has never been studied extensively. On theoretical grounds, it can also be hypothesized that molar ratios of these peptides might be of additional value. DESIGN: Retrospective, multicentre, cohort study. PATIENTS: 96 children evaluated for short stature. METHODS: Serum IGF-I, IGF-II, IGFBP-3 and various molar ratios were, after correction for age and sex using SD scores, compared to the maximum serum GH peak after two standard provocation tests using four different methods (t-test, chi2, likelihood ratios and ROC curves). In addition, the correlations between these parameters and the short-term (1 year) and long-term (3 years) response to GH therapy were calculated. RESULTS: IGF-I performed better than IGFBP-3, but the best results were achieved by the molar ratio IGF-I:IGF-II. However, IGFBP-3 correlated better with the short-term response to GH therapy than IGF-I or the ratios, and none of the parameters investigated was found to be related to the response of long-term GH therapy.

Adolescent↗
PubMed1997

CMO I deficiency caused by a point mutation in exon 8 of the human CYP11B2 gene encoding steroid 18-hydroxylase (P450C18).

Corticosterone methyloxidase I (CMO I) deficiency is an autosomal recessive disorder of aldosterone biosynthesis. To determine further the molecular genetic basis of CMO I deficiency, a patient of Turkish origin that suffered from CMO I deficiency was studied. Nucleotide sequencing of the PCR-amplified exons from the genomic DNA of this patient revealed a single point mutation CTG (leucine) CCG (proline) at codon 461 in exon 8 of CYP11B2, which is involved in the putative heme binding site of steroid 18-hydroxylase (P450(C18)). The expression study using a cDNA introducing the point mutation revealed that the amino acid substitution totally abolishes the P450(C18)p3 enzyme activities required for conversion of 11-deoxycorticosterone to aldosterone, even though the mutant product was detected in the mitochondrial fraction of the transfected cells. These results suggest that this point mutation causes CMO I deficiency.

Aldosterone↗
PubMed1997

Effects of beta-IFN-1b treatment in MS patients on adhesion between PBMNCs, HUVECs and MS-HBECs: an in vivo and in vitro study.

The in vivo effects on the expression of adhesion molecules and on the adhesion between mononuclear cells and multiple sclerosis human brain endothelial cells (MS-HBECs) were investigated at the beginning of beta-IFN-1b treatment of MS patients. MS-HBECs were isolated from a surgical specimen obtained from an MS patient undergoing brain surgery for vascular aneurysm. 48 h after the first single administration of beta-IFN-1b, PBMNCs of 10 MS patients were analyzed for HLA-DR, CD11a, CD18 and VLA-4 expression and the adhesion between PBMNCs and both stimulated and unstimulated MS-HBECs evaluated. sICAM-1 and sVCAM-1 dosage in the serum of the patients was checked as well. The experiments were repeated using HUVECs in order to detect possible endothelial organ-specific differences. The experiments were also performed after six months of beta-INF-1b treatment on HUVECs. No significant effects on mononuclear cells/endothelium adhesion were detected at 48 h, but adhesion of PBMNCs to HUVECs decreased at six months. An increase in HLA-DR and VLA-4 and a decrease of CD18 was detected in monocytes. The serum level of sVCAM-1 increased at T2 and was still higher than at T0 at six months. The effect of the beta-IFN-1b treatment on both MS-HBECs and HUVECs, was selectively studied in vitro by testing the expression of cytokine-induced adhesion molecules HLA-DR, ICAM-1 and VCAM-1. The in vitro experiments confirmed that beta-IFN-1b is able to antagonize gamma-IFN-induced HLA-DR expression on MS human brain endothelial cells without relevant effects on VCAM-1 and ICAM-1.

Adult↗
PubMed1997

Reduced adhesion of PBMNCs to endothelium in methylprednisolone-treated MS patients: preliminary results.

Methylprednisolone (MP) is a synthetic steroid commonly used in the treatment of multiple sclerosis (MS) relapses. It has a wide spectrum of activities on immune cells: it might also act by preventing mononuclear cell/endothelium adhesion. We studied adhesion phenomena between cultured human umbilical vein endothelial cells (HUVECs) and PBMNCs (CD45+, CD14+) from 6 MS patients treated in vivo with MP. We also studied fluctuations in CD11a and CD18 levels on lymphocytes and monocytes, as well as changes in serum sICAM-1 and sVCAM-1 concentrations. After MP treatment, PBMNCs adhesion to endothelium decreased at 3 h, while it went back to baseline levels at 24 h. A tendency to increase in both CD11a and CD18 on the surface of lymphocytes was detected, while an increase in serum sVCAM-1 was seen at 3 h.

Adult↗
PubMed1997

Reference values for height, height velocity and weight in Turner's syndrome. Swedish Study Group for GH treatment.

As Northern Europeans are currently the tallest people in the world, specific growth charts for girls with Turner's Syndrome from this area are needed. Based on height and weight measurements from 598 girls with Turner's Syndrome (372 from the Netherlands, 108 from Denmark, 118 from Sweden) not treated with growth-promoting substances and without signs of spontaneous puberty, we constructed growth charts for height-for-age, height-velocity-for-age, weight-for-age, weight-for-height and Body Mass Index for age. Reference tables and regression equations for mean and standard deviation are provided allowing calculation of Standard Deviation Scores. The height and height velocity curves show a low birth length, gradual deviation from the normal percentile curves without pubertal growth spurt, and a prolonged growth until the early 20s. Mean adult height was 146.9 +/- 7.8 cm. Mean weight-for-age was lower than in normal reference children but height-adjusted weight was higher, except in infancy and early childhood. Further studies are required on the factors influencing the weight-height relationship in Turner's Syndrome.

Adolescent↗
PubMed1997

A valuable improvement of adult height prediction methods in short normal children.

OBJECTIVES: The potential benefit of growth hormone (GH) administration to increase adult height of normal children of short stature might be blurred by the accuracy and the precision of the prediction methods used to estimate final height before onset of therapy. The aim of the present study was to evaluate three prediction methods: Bayley-Pinneau (BP), Roche-Wainer-Thissen (RWT) and Tanner-Whitehouse Mark II (TW2) and to improve their accuracy and precision by exploring their correlation with various parameters obtained in peripubertal children with poor predicted adult height. STUDY DESIGN: Accuracy and precision of the prediction methods were evaluated retrospectively by comparing predicted adult heights estimated in 62 boys at 13.7 +/- 0.9 years and in 28 girls at 12.1 +/- 0.9 years of age, with their adult heights measured respectively at 20.7 +/- 2.6 years and 18.8 +/- 2.8 years. RESULTS: At the time of prediction, the height for chronological age was -2.07 +/- 0.68 standard deviation scores for boys and -2.15 +/- 0.6 years for girls. Measured adult heights were significantly lower than target heights (165.1 +/- 5.1 vs. 169.4 +/- 4.8 cm for boys; p < 0.001 and 153.1 +/- 3.9 vs. 156.3 +/- 5.0 cm for girls; p = 0.001). For boys, the BP method was the most accurate and also the most convenient with a predicted adult height of 164.7 +/- 5.0 cm and a small underestimation of 0.4 +/- 3.5 cm. For girls, the TW2 method was the most accurate with a predicted height of 152.4 +/- 3.7 cm with a little underestimation of 0.7 +/- 3.5 cm. There were no important differences between the precision of these methods. The use of a correction factor derived from the bone age delay at the time of prediction in boys and from the chronological age at the time of prediction in girls improved the accuracy of the predicted adult height. CONCLUSIONS: The use of a factor correcting the accuracy of the BP method in boys and of the TW2 method in girls should be valuable in assessing the potential benefit of GH therapy to increase adult height in short normal children.

Adolescent↗
PubMed1997

Growth before and during growth hormone treatment in children operated for craniopharyngioma.

Height and weight growth before and during treatment with human growth hormone (hGH) was studied in 46 Dutch patients treated for craniopharyngioma. Weight was expressed as body mass index (BMI, weight/height). At the time of tumor treatment mean +/- SD height standard deviation score (SDS) was -1.22 +/- 1.38 and BMI SDS was 0.56 +/- 1.32. The initial height SDS was inversely related to age (r = -0.38; p < 0.02). Before hGH treatment height SDS decreased to - 1.57 +/- 1.08 (p < 0.05) and BMI SDS increased to 1.54 +/- 1.58 (p < 0.005) during the first year after tumor treatment. Changes in height SDS correlated positively with basal prolactin (PRL) levels (r = 0.46; p < 0.05). Neither tumor localization nor treatment mode was related to changes in height SDS and BMI SDS. Forty patients were treated with hGH, started a median interval of 2.0 years after tumor treatment. At the time of the start of hGH treatment height SDS in these patients was -1.70 +/- 1.13, and BMI SDS was 1.44 +/- 1.79. During treatment with hGH, height SDS increased to -1.05 +/- 1.10 (p < 0.001) in the first, and to -0.80 +/- 1.04 (p < 0.001) in the second year. BMI SDS did not change during hGH therapy. In conclusion, there is a large variation in height SDS and BMI SDS at the time of initial presentation as well as during spontaneous growth after tumor treatment. Spontaneous growth is related to serum PRL concentrations. Treatment with hGH significantly increased height SDS during the first 2 years, whereas BMI SDS did not change.

Adolescent↗