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Biomedical subjects

P Brambilla

Publications and source records attributed to P Brambilla.

At least 19 recordsLinked to original sources
PubMed1995

Insulin regulation of glucose turnover and lipid levels in obese children with fasting normoinsulinaemia.

To evaluate the early metabolic alterations induced by obesity, we studied glucose turnover and lipid levels in obese children with fasting normoinsulinaemia. Two experimental protocols were carried out. Protocol I consisted of a euglycaemic glucose clamp at two rates of insulin infusion. Protocol II was similar to protocol I except for a variable lipid infusion used to maintain basal non-esterified fatty acid (NEFA) levels. During protocol I, the glucose disappearance rates were lower in obese children, while no differences were found in hepatic glucose release. NEFA response to insulin was not substantially altered in obese children either at low or high insulin infusion. During protocol II, the NEFA clamp induced a 25% reduction in peripheral insulin sensitivity in control children whereas no changes were observed in obese children. Interestingly, lipid infusion in control children was not sufficient to reproduce the same degree of insulin resistance observed in obese children, suggesting that NEFA are only one of the determinants of insulin resistance at this stage of obesity. In conclusion, the present study provides a portrait of glucose metabolism and lipid levels in normoinsulinaemic obese children. Our results document that peripheral insulin resistance is the first alteration at this stage of obesity, whereas an increase in insulin secretion and a defect in the inhibition of hepatic glucose release by insulin may develop at a later stage. In addition, primarily receptor and post-receptor defects and some alterations of NEFA metabolism are likely to coexist in the induction of insulin resistance at this stage of obesity.

3-Hydroxybutyric Acid↗
PubMed1995

Relative expansion of extracellular water in obese vs. normal children.

This preliminary communication reports data regarding the distribution between intracellular (ICW) and extracellular (ECW) water compartments in a group of 21 prepubertal young obese children of both sexes in comparison with a group of 18 normal children weight matched for age. Our data indicate that obesity is associated with a highly significant relative expansion of extracellular water (ECW/ICW = 0.61 +/- 0.19 and 0.76 +/- 0.09 in control and obese subjects, respectively; P < 0.0015). This observation, which has been already reported in adult women, suggests that some disturbances of water homeostasis have an early onset and stress the need for an early control of energy imbalance in children. These findings are of great concern also in the field of human body composition, suggesting the opportunity for a critical reevaluation of the assumed constancy of some human body characteristics. Body composition methodologies developed for "normal" populations would require adjustment for use in the obese population, since a considerable error would be introduced.

Body Water↗
PubMed1992

Determination of plasma [6,6-2H2]glucose enrichment by a simple and accurate gas chromatographic-mass spectrometric method.

An improved method for the evaluation of glucose turnover rate in humans, using a prime-continuous infusion of [6,6-2H2]glucose, was developed. Deproteinization of plasma and conversion of glucose into the aldononitrile pentaacetate derivative are the only sample manipulations required prior to the gas chromatographic-mass spectrometric analysis. In six normal adults (prime = 5 mg kg-1; continuous infusion = 0.05 mg kg-1 min-1) the hepatic glucose output calculated at steady state by the procedure described here was 2.1 +/- 0.2 mg kg-1 min-1, the isotopic enrichment being determined with a coefficient of variation of ca. 2%. In six additional subjects, with half of the above-mentioned doses of labelled glucose, the mean hepatic glucose output was exactly the same (3.2% coefficient of variation for the isotopic enrichment measurement). The method described allows the hepatic glucose output to be precisely determined with savings both of time and of labelled glucose.

Blood Glucose↗
PubMed1992

Establishment and characterization of a new murine cell line (SR-4987) derived from marrow stromal cells.

A new murine cell line designated as SR-4987 was established by treating a long-term bone marrow culture with the supernatant from Y-1 cells which actively produce viral C-particles (MuLV). The line showed a fibroblast-like morphology and its mesodermal origin was confirmed by immunocytochemical staining. Flow cytometric analysis of DNA index evidenced a tetraploid number of chromosomes whereas cell cycle analysis showed 34.8% of cells in S phase and 60.7% in G1. In vitro growth studies demonstrated a population doubling time of 14.7 h, a good plating efficiency (52.3%) and a very poor agar clonogenic capacity (0.6%). SR-4987 was tumorigenic only in syngeneic mice in which sarcomas were induced. The line produced M-CSF in the culture supernatant whereas G-CSF, IL-3 and GM-CSF were not detected. Studies are in progress to assess the production of other cytokines and to verify if same autocrine growth factor is involved in the control of SR-4987 proliferation. Our line provides a further model of stromal cells for studying the interaction between hemopoietic progenitors and their microenvironment, as well as to study factors produced by stromal cells acting as modulators of proliferation and differentiation of related cell populations.

Animals↗
PubMed1992

Echocardiographic parameters and indices in the normal beagle dog.

M-mode and two-dimensional echocardiographic measurements were made from the right sternal border of 50 healthy Beagles (25 males and 25 females) approximately 7 months old. The dogs were conscious and standing during the investigation. The following parameters, in systole and diastole, were measured on the echocardiographic images: left ventricular posterior wall thickness (LVWT); intraventricular septum thickness (IST); left ventricular internal dimension (LVID); and circumference (LVC). Fractional shortening (FS) and ejection fraction (EF) were also calculated. Mean, standard deviation, range and coefficient of variation are reported for each echocardiographic parameter and for body weight. Males and females were considered separately and together. Each parameter was analysed statistically to check for differences between the sexes and for correlations with body weight. A statistically significant difference between the sexes was only observed for LVWT in systole and diastole. A linear regression with body weight was obtained only for LVID in systole and in diastole. The results show that morphofunctional cardiac homogeneity is independent of size in dogs of this breed and age.

Analysis of Variance↗
PubMed1992

The prediction of total body water from body impedance in young obese subjects.

Almost all formulae for the prediction of total body water (TBW) from body impedance are based on the assumption of a constant conductor configuration--i.e. a constant subject section. In this paper we report on data obtained for a group of 19 young obese subjects (relative weight greater than 120%) and 10 young normal subjects (relative weight 80-110%). In obese subjects, the application of two different formulae generated from normal children gave biased results and led to an underestimation of TBW with respect to the reference value obtained by deuterium oxide dilution. Body mass index accounted for more than 40% of the inter-individual variability, suggesting that body size was not taken sufficiently into consideration by the predictive formulae used. We have used the body surface area as the anthropometrical parameter for the prediction of TBW from body impedance. The regression formula that we propose (TBW = 1.156 x (surface area/body impedance) - 2.356; R = 0.96), although requiring further validation on external populations, seems to provide a more realistic assessment of TBW in young obese subjects. We therefore suggest that the assessment of TBW in young obese subjects requires specifically designed prediction formulae.

Adolescent↗
PubMed1992

[Changes in dynamic respiratory volumes in obese children and adolescents related to weight loss and sex].

Obesity is associated with various alterations in lung function in adults. These alterations appear to be proportional to the degree of EP and the beneficial effect of weight loss on respiratory function has been reported. Therefore, in 35 children and adolescents affected by essential obesity of medium-severe degree, we have evaluated the following parameters: FVC (forced vital capacity), PEF (peak expiratory flow), FEV1 (forced expiratory volume), FEV75, FEV50, FEV25, before and after six months of dieting. Twelve subjects (34%) showed at least a pathologic value of PEF and/or FEV50 before dieting. All the female patients normalized their parameters after six months of dieting, whilst 5 out of 7 males still showed pathologic respiratory indexes, although a similar weight loss was obtained in the two groups of patients. Our study enhances the presence of respiratory functions derangements in a significant percentage of children with medium-severe degree of obesity. A careful monitoring of these subjects is therefore necessary, in order to prevent further progression of the lung function damage. After dieting the pulmonary function improved in female patients only, suggesting that factors other than the EP are involved in the pathogenesis of the respiratory alterations.

Adolescent↗
PubMed1991

cdc2 phosphorylation is required for its interaction with cyclin.

Activation of the cdc2 protein kinase at different stages of the cell cycle is regulated by post-translational modifications and interactions with cyclins. We show that in vitro translated human cdc2 binds very poorly to A and B cyclins, unless it has been preincubated with a Xenopus egg extract. This results in the phosphorylation of cdc2 which allows binding to cyclins. The replacement of Thr161, a residue conserved and phosphorylated in other protein kinases, with valine inhibits cdc2 association with A and B cyclins. In addition, mutations in the amino-terminus of cdc2 and within the conserved 'PSTAIR' region strongly inhibit binding. The Thr161Val mutation causes a lethal phenotype in the fission yeast Schizosaccharomyces pombe, while replacement of Thr161 with glutamic acid, potentially mimicking phosphorylation, causes uncoordination of mitosis and multiple cytokinesis. These results suggest that a threonine phosphorylation/dephosphorylation cycle is involved in regulating cdc2 function.

Amino Acid Sequence↗
PubMed1991

Serum concentrations of 2,3,7,8-tetrachlorodibenzo-p-dioxin and test results from selected residents of Seveso, Italy.

2,3,7,8-Tetrachlorodibenzo-p-dioxin levels (TCDD) were measured in serum specimens from Seveso, Italy, residents, who were potentially highly exposed to the 1976 explosion, and in controls. The residents were chosen so as to represent those who did and did not develop chloracne. Levels of TCDD as high as 56,000 parts per trillion (ppt) were found in these serum specimens that were collected in 1976. These TCDD levels are the highest ever reported, and yet almost all clinical laboratory tests on these individuals were normal; any abnormal test result was only transitory in nature. These findings are unique in linking clinical histories to TCDD levels following an acute exposure.

Accidents↗
PubMed1991

Mutations at sites involved in Suc1 binding inactivate Cdc2.

suc1+ encodes an essential cell cycle regulator of the fission yeast Schizosaccharomyces pombe. Its product, a 13-kDa protein, interacts with the Cdc2 protein kinase. Both positive and negative effects on cell cycle progression have been attributed to Suc1. To date, the exact mechanisms and the physiological role of the interaction between Suc1 and Cdc2 remain unclear. Here we have studied the molecular basis of this association. We show that Cdc2 can bind Suc1 or its mammalian homolog directly in the absence of any additional protein component. Using an alanine scanning mutagenesis method, we analyzed the interaction between Cdc2 and Suc1. We show that the integrity of several domains on the Cdc2 protein, including sites directly involved in catalytic activity, is required for binding to Suc1. Furthermore, Cdc2 mutant proteins unable to bind Suc1 (but able to bind cyclins) are nonfunctional when overexpressed in S. pombe, indicating that a specific interaction with Suc1 is required for Cdc2 function.

Amino Acid Sequence↗
PubMed1990

[Screening for obesity in a schoolchildren population of the 20th zone of Milan and a nutritional education intervention].

Our study was performed in 1986-'87 and 1987-'88 school years on 12.354 three to eighteen years old students (the whole scholastic population of zone 20 of Milan) in order to apply dietary education on obese subjects. Mean prevalence of obesity was 13.4% with elevated percentages in 11 to 13 years old students (17.9%), with respect to primary (14.1%), high school (12.4%) and nursery school (4.7%). The 36% of obese subjects (more than 50% of adolescents) had already tempted to reduce body weight. Intervention reduced % weight excess (from 33.6 +/- 0.5% to, 28.8 +/- 0.5% after 12 months, p less than 0.001); 67% of obese subjects lost weight and body weight returned within normal limits in 31% of subjects. An educational dietetic strategy may be successful in childhood obesity.

Adolescent↗
PubMed1988

A new method for D-glucaric acid excretion measurement that is suitable for automated instruments.

Urinary excretion of D-glucaric acid (uGA) is an index of type II hepatic microsomal enzyme induction, indirectly revealing possible organic effects of some drugs and environmental pollutants. However, its determination is often cumbersome. We suggest a new, fast microanalytical method for uGA determination in which beta-glucuronidase (BG; EC 3.2.1.31) activity inhibition produced by uGA-derived 1,4-D-glucarolactone is measured. With use of purified BG, the method is suitable for centrifugal analyzers, allowing assay of greater than 100 samples per day. Moreover, the method measures uGA more accurately than other enzymatic methods based on BG inhibition. The within-day CV ranges from 7.9% to 4.6% (uGA 31.55-121.31 mumol/L); the between-day CV ranges from 11.5% to 5.0% (uGA 26.09-124.10 mumol/L). The detection limit is 6.0 mumol/L. The standard curve is linear from 10 to 200 mumol/L. Mean analytical recovery is 100%. Comparison with the method of Simmons et al. (Clin Chim Acta 1974;51:47-51) gave a correlation of r = 0.978, y = 1.40x-2.81. Reference intervals were established in a healthy population sample of 369 people (165 under 14 y), and uGA, expressed in micromoles per gram of creatinine, was higher in women than in girls or in males.

Adolescent↗
PubMed1987

Glucose counterregulation in pre-school-age diabetic children with recurrent hypoglycemia during conventional treatment.

To determine whether immature or defective glucose counterregulation was responsible for the severe recurrent hypoglycemic episodes (3.6 per patient per year) observed during conventional therapy (CT) in six pre-school-age diabetic children, we investigated their metabolic and hormonal responses to insulin infusion (40 mU/kg i.v. for 60 min). Counterregulation was considered adequate because no patient experienced symptoms requiring discontinuation of the test, and blood glucose (BG) nadirs averaged 42 +/- 5 mg/dl. Glucose production rate decreased from 4.2 +/- 0.2 to 2.6 +/- 0.6 mg X kg-1 X min-1. Blood 3-hydroxybutyrate levels were elevated (approximately 3 mM) and did not change during insulin infusion. The responses of epinephrine (from 137 +/- 37 to 393 +/- 143 pg/ml), norepinephrine (from 145 +/- 33 to 347 +/- 152 pg/ml), and growth hormone (from 6.0 +/- 1.5 to 20.3 +/- 5.1 ng/ml) were normal for this age group. As previously observed in diabetic adults, glucagon response was deficient (from 117 +/- 30 to 114 +/- 18 pg/ml). The six children were subsequently treated with continuous subcutaneous insulin infusion (CSII), which resulted in a 20-fold decrease in the number of severe hypoglycemic reactions. Predisposition to severe hypoglycemia in this subset of diabetic children, which remains a refractory problem even after considerable efforts have been made to decrease them, may thus be sharply decreased with CSII therapy. During this therapy, a significant inverse correlation appeared between the individual frequency of BG values less than 40 mg/dl and BG nadir during the insulin infusion test (r = .94, P less than .001).

Blood Glucose↗