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Biomedical subjects

G Galli

Publications and source records attributed to G Galli.

At least 109 records · Page 6Linked to original sources

Wilms' tumor involving the inferior vena cava: preoperative evaluation and management.

Neoplastic invasion of the inferior vena cava due to renal tumors (especially Wilms' tumor) is uncommon in children. The tumor thrombus, according to the aggressiveness of the original neoplasm, can extend in diverse ways, obliterate the vascular lumen completely, and even reach the right atrium. The luminal thrombus might be accompanied by the involvement of the caval wall, which requires wide vascular resection. The purpose of this paper is to present our experience with 7 children, aged 18 months and 6 years, affected by caval invasion due to Wilms' tumor. Furthermore, the diagnostic techniques and the surgical treatment in simple caval thrombosis and in associated invasion of the caval wall are described.

Child↗

Short cycles of very low calorie diet in the therapy of obese type II diabetes mellitus.

Very Low Calorie Diet (VLCD) is known to induce not only weight loss, but also an improvement of metabolic control, in obese type II diabetics. In order to evaluate the therapeutical efficacy of cycles of VLCD shorter than those previously described, 29 obese type II diabetics and 31 obese nondiabetic subjects were entered as inpatients and prescribed a 450 kcal/day diet for 15 days. Metabolic results obtained were similar to those achieved with longer cycles of VLCD, showing that 15 days are sufficient to induce a BMI decrease in diabetic (BMI from 35.3 +/- 4.8 to 33.3 +/- 4.6 after VLCD) and nondiabetic patients (BMI from 40.5 +/- 7.4 to 38.1 +/- 7.2 after VLCD), a desired fall of blood glucose levels and the decrease of daily insulin needs in insulin-treated patients. Glucagon tests were performed before and after VLCD in order to study possible modifications of insulin secretion. Although we did not observe any significant increase of C-peptide basal or peak levels (nM/ml) either in diabetic (basal levels before VLDC: 1.2 +/- 0.4 and peak levels 2.4 +/- 0.7; basal after VLCD 1.23 +/- 0.6 and peak 2.6 +/- 0.7) and nondiabetic patients (basal levels before VLDC 1.0 +/- 0.3 and peak levels 2.5 +/- 0.4; basal after VLCD 0.9 +/- 0.3 and peak 2.4 +/- 0.6). The rise of the C-peptide/glycemia ratio is an index of an improvement of insulin biological activity, which could be partly responsible for the therapeutical effects of VLCD.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Adrenocortical tumors in children: a report of 12 cases.

Adrenocortical tumors in children are extremely rare, accounting only for 0.3-0.4% of all neoplasms in this age. Most frequently they secrete hormones, resulting in virilization, Cushing's syndrome or feminization, while the non-functioning ones are unusual. The authors describe 12 cases observed in 13 years (1976-1989), with a mean age of 5 years. 9 cases showed virilization, 4 presented with Cushing's syndrome and in 5 patients an abdominal mass was palpable. One case was affected by Beckwith-Wiedemann's syndrome. I.V. urography was performed in 8 patients, arteriography in 4 and since 1982 all patients were submitted to abdominal sonography and CT scan or MR imaging. Urinary 17-ketosteroids, 17-hydroxycorticoids and serum testosterone and cortisol were tested in all children. Dexamethasone suppression test was performed in 7. All patients were treated with surgery which seems to be the most suitable treatment, while the real effectiveness of treatment by drug therapy with suppressors of steroidogenesis is not confirmed in children. Histopathological examination showed typical features of adenoma in 5 cases, of adenocarcinoma in 4, while three cases revealed border line forms classified as "atypical adenomas". At the moment 10 patients are alive with a follow-up ranging from 18 months to 14 years, while 2 children with adenocarcinoma are dead.

Adenocarcinoma↗

Allergenic potential of gonadotrophic preparations in experimental animals: relevance of purity.

Local reactions have been frequently reported following repeated injections of human menopausal gonadotrophins (HMG) for the treatment of infertility. Also immunoglobulin (Ig) E-mediated systemic reactions have sporadically been observed. Since most HMG preparations contain significant amounts of non-hormonal urine-derived proteins, it was suggested that these contaminating proteins are responsible for the various allergic reactions. In order to verify this hypothesis, different human follicle stimulating hormone (HFSH) and HMG preparations (Metrodin and Pergonal from Ares-Serono, and Humegon from Organon), were compared with a highly purified preparation (Metrodin HP from Ares-Serono) for the frequency and severity of allergic reactions induced in laboratory animals. The occurrence of anaphylactic shock or related symptoms was studied in sensitized guinea-pigs. The production of specific IgE was evaluated in serum from mice sensitized with the test drugs by the induction of passive cutaneous anaphylaxis in rats. In both models, two different schedules of sensitization were used. Severe allergic reactions were found in 20 of 7% of the guinea-pigs receiving highly purified FSH (Metrodin HP) in the two schedules, respectively, compared to 90 and 88% with the other preparations. Similarly significantly lower IgE titres were induced by highly purified FSH in respect to the other preparations. It can be concluded that the elimination of contaminating proteins significantly reduces the allergenicity of urine-derived HFSH preparations.

Anaphylaxis↗

A simplified determination of glomerular filtration rate with 99Tcm-DTPA.

Using 99Tcm-diethylenetriaminepentaacetate (DTPA) an acceptable estimate of glomerular filtration rate (GFR) can be obtained in adult patients by the equation GF (ml/min) = (0.14 x W + 5) x 1000 x k, where W is the 'ideal' body mass (kg) and k the slope determined by two plasma samples. This has been verified in comparison with the results of the Russell (two samples) and Christensen (one sample) methods in 50 patients. The procedure, which does not require determination of the injected dose, could be useful in patients undergoing sequential renal scintigraphy with 99Tcm-DTPA, for example, to check a doubtful value of glomerular filtration obtained by external counting.

Adult↗

Characterization of insulin-like growth factor-binding proteins produced by cultured fibroblasts from patients with noninsulin-dependent diabetes mellitus, insulin-dependent diabetes mellitus, or obesity.

To evaluate whether the production of insulin-like growth factor-binding proteins (IGFBPs) is altered in various pathological states due to modification of the hormonal milieu, we analyzed patterns of IGFBPs released into conditioned medium during 48-h serum-free culture of early passages of human skin fibroblasts from control subjects and patients with metabolic disorders. IGFBP-2, -3, -4, and -5 were identified in the conditioned medium by immunoblotting or RIA. Compared with those in eight control subjects by ligand blot analysis, the levels of IGFBP-3, -2, and -5 were reduced to 43%, 47%, and 53% in 10 noninsulin-dependent diabetic patients, respectively, whereas the levels of IGFBP-3 and -2 were reduced to 36% and 23%, respectively, in 3 nondiabetic obese patients with impaired glucose tolerance. In 2 insulin-dependent diabetic patients, the level of IGFBP-3 was reduced by 25% and 40%, respectively, and IGFBP-2 was not detectable. In contrast, a similar level of IGFBP-4 was detected in both normal and patient's conditioned media, except in 1 insulin-dependent diabetic patient. These data indicate that fibroblasts derived from patients with metabolic disorders retain their intrinsic characteristics even after they are removed from their in vivo hormonal milieu.

Adult↗

Mechanisms of glucose-enhanced extracellular matrix accumulation in rat glomerular mesangial cells.

In view of the importance of mesangial extracellular matrix (ECM) accumulation in the pathogenesis of diabetic glomerulosclerosis, we investigated 1) the effects of high glucose on ECM production by rat glomerular mesangial cells in culture (study A) and 2) the mechanisms underlying these effects, particularly the role of high sugar levels irrespective of intracellular metabolism (study B1) and of excess glucose disposal via the polyol pathway and associated biochemical alterations (study B2). Cells were cultured for 4 weeks, through six to eight passages, under the experimental conditions indicated below and, at each passage, the levels of fibronectin (FN), laminin (LAM), and collagen types I (C-I), III (C-III), IV (C-IV), and VI (C-VI) in media and cell extracts were quantified by an enzyme immunoassay. In study A, medium and cell content of matrix were assessed, together with [3H]leucine and [3H]thymidine incorporation into monolayers, polyol, fructose, and myo-inositol levels and the cytosolic redox state, in cells grown in high (30 mM) D-glucose or iso-osmolar mannitol versus cells cultured in normal (5.5 mM) D-glucose. FN, LAM, C-IV, and C-VI accumulation, but not C-I and C-III accumulation, was increased by 30 mM glucose, but not by iso-osmolar mannitol, when compared with 5.5 mM glucose, starting at week 2 and, except for C-VI, persisting throughout the remaining 2 weeks, whereas no change was observed in the measured indexes of total protein synthesis and DNA synthesis/cell proliferation. At any time point, polyol levels were increased, whereas myo-inositol was reduced by high glucose; in cells grown under elevated glucose concentrations, the lactate/pyruvate (L/P) ratio, an index of the cytosolic redox state, progressively increased. In study B1, the effects of high D-glucose were compared with those of iso-osmolar concentrations of sugars that are partly or not metabolized but are capable of inducing nonenzymatic glycosylation, such as D-galactose and L-glucose, and of mannitol, which does not enter the cell. Both D-galactose and L-glucose, but not mannitol, partly mimicked D-glucose-induced ECM overproduction. Although D-galactose is metabolized via the polyol pathway and alters the cytosolic redox state, ECM changes induced by high galactose were not prevented by the use of an aldose reductase inhibitor (ARI), Alcon 1576 (14 microM).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Determination of glomerular filtration rate with 99mTc-DTPA in clinical practice.

In order to assess the practical reliability of glomerular filtration rate (GFR) determination with 99mTc-DTPA and plasma sampling, the authors compared the results obtained with 51Cr-EDTA and 99mTc-DTPA in 50 patients using five easily applied methods (two double-plasma-sample methods and three single-plasma-sample methods), and two kits with different compositions. It was observed that: 1) there is no difference between the results obtained with the two different kits. 2) Compared with 51Cr-EDTA the 99mTc-DTPA overestimates the result by about 2 mL/min: precision is slightly lower with 99mTc-DTPA than with 51Cr-EDTA but is sufficient for practical use. 3) The method recommended by the authors on the basis of this experience is the Russell's method with two samples. 4) The simplified methods with one sample give comparable results to the Russell's method for GFR levels between 50 and 115 mL/min, while the results are unsatisfactory below 50 mL/min. 5) Among the single-sample methods, the authors suggest that of Christensen and Groth. 6) A preliminary estimate of GFR (from the serum creatinine level, for instance) is useful for the choice between double-plasma-sample methods and simplified methods. In conclusion, the authors consider that the estimation of GFR with 99mTc-DTPA can be performed efficiently in clinical practice even when operating in absolutely routine conditions.

Chromium Radioisotopes↗

Acetaldehyde induces c-fos and c-jun proto-oncogenes in fat-storing cell cultures through protein kinase C activation.

Hepatic fibrosis is an important morphological feature of alcohol-induced liver injury. We previously reported that acetaldehyde stimulates collagen I and fibronectin gene transcription in rat fat-storing cell (FSC) culture. We here evaluated whether acetaldehyde increases Col I and FN gene transcription through the induction of c-fos and c-jun proto-oncogenes and studied the possible role played by protein kinase C (PKC) and c-AMP. FSCs, isolated from rat liver on a Nycodenz density gradient, were exposed to acetaldehyde for 1/2, 1, 3, 6, 12, 24 hr and for 10, 20, 30, 45, 60, 90 min in the experiments for jun and fos expression, respectively. Acetaldehyde produced a rapid and transient induction of fos mRNA (undetectable at t = 0, peak at t = 45 and still evident at t = 90). Jun mRNA was weakly expressed in unstimulated FSCs; acetaldehyde induced a prolonged activation of jun expression up to 24 hr with a peak at 3 hr. To study the role of PKC were repeated the experiments in the presence of Staurosporine and H-7. These inhibitors of PKC activity blocked the stimulatory effect of acetaldehyde on fos and jun mRNA expression. Furthermore, they abolished the stimulatory effect of acetaldehyde on collagen I and fibronectin gene expression by FSCs. Acetaldehyde increased the cell membrane PKC activity in FSC cultures in a dose-dependent way. Intracellular cAMP levels were not significantly modified by acetaldehyde in the first 30 min of incubation. We conclude that acetaldehyde increases procollagen I and fibronectin gene transcription in FSCs, possibly through c-fos and c-jun expression, and that PKC may play a regulatory role in this chain of events.

Acetaldehyde↗

[Subarachnoid hemorrhage: assessment in the acute phase with angiography, with high-resolution magnetic resonance (angio-MR)].

Previous reports demonstrated that Magnetic Resonance Angiography (MRA) is a reliable means of diagnosing intracerebral aneurysms. However, in these early studies MRA was performed in patients with cerebral aneurysms already proved by intraarterial angiography. Our study was aimed at investigating the clinical feasibility and the diagnostic accuracy of high-resolution MRA in patients with acute subarachnoid hemorrhage. Twenty-five patients (15 women, 10 men) with CT diagnosis of subarachnoid hemorrhage were prospectively examined with high-resolution MRA within 24 hours of bleeding. All patients underwent intraarterial digital subtraction angiography (IA DSA) immediately after MRA examination. MRA studies were performed with a 1.5-T unit. MRA examinations of the cerebral vessels consisted of axial excitation of two 50-mm volume slabs, with 25% overlap, covering the cerebral circulation from the vertebro-basilar junction to the pericallosal artery. Pulse sequence variables were optimized to reduce voxel size (0.62 x 0.62 x 0.78) and to increase spatial resolution (160-mm FOV, 256 x 256 matrix, 0.78-mm slice thickness) while keeping S/N ratio high. The maximum intensity projection (MIP) reconstruction algorithm was used. The examination lasted nearly 20 minutes. Four MRA examinations (16%) were considered inadequate for diagnosis because of motion artifacts. High-resolution MRA detected 20 of 21 aneurysms in 17 patients, with 1 false positive and 1 false negative. Two patients had multiple aneurysms, 2 and 4 respectively, all of them detected by MRA. No cause of subarachnoid hemorrhage was found by IA DSA in 4 patients, while MRA studies were considered negative in 3 patients. Nineteen aneurysms were surgically clipped, while 2 basilar artery aneurysms were occluded by intravascular treatment. MRA and DSA findings were compared with surgical findings. Relative to IA DSA, MRA exhibited 95% sensitivity and 95% specificity. Aneurysm size ranged 2-10 mm: the smallest aneurysm detected by MRA was 2.5 mm. Anatomical and morphological agreement between MRA and IA DSA was excellent, with only slight MRA underestimation of the aneurysm size in 25% of cases and overestimation in 15% of cases. The aneurysm neck was shown by MRA in 60% and by IA DSA in 81% of cases. High-resolution MRA proved to be especially useful in complex anatomical sites where the direction of the aneurysm could be clearly demonstrated through the accurate selection of the appropriate projection angle and the careful examination of direct axial images.(ABSTRACT TRUNCATED AT 400 WORDS)

Acute Disease↗

Genomic cloning, sequencing, and analysis of the hamster cholesterol 7 alpha-hydroxylase gene (CYP7).

Cholesterol 7 alpha-hydroxylase is the rate limiting enzyme in bile acid biosynthesis and plays an important role in cholesterol homeostasis. The Golden Syrian hamster has been used as an animal model for the study of atherosclerosis and cholesterol gallstone disease. We have screened a lambda DASH II hamster liver genomic library using a rat cDNA as a hybridization probe. A 14-kb genomic clone has been isolated and characterized by restriction mapping and Southern blot hybridization. The clone contained the full-length gene encoding cholesterol 7 alpha-hydroxylase together with an upstream sequence of approximately 5 kb. DNA sequencing and analysis of about 11 kb of the gene revealed that the hamster CYP7 gene consists of six exons and five introns, which have the same structures and sizes as predicted in the rat and human CYP7 genes. The nucleotide and deduced amino acid sequences of the hamster cholesterol 7 alpha-hydroxylase have a high sequence identity of about 90% to the rat and 82% to the human sequences. Particularly, exons 2, 5, and 6 are highly conserved among these species, thus reflecting the presence of some domains that are crucial for the activity of this unique enzyme. The putative cholesterol-binding region, an aromatic amino acid region, and the P450 heme-binding region are completely conserved. Comparison of the 250-bp 5'-flanking sequence to the corresponding region in the rat and human genes revealed a high degree of homology ranging between 71% and 82%. Next to the canonical TATA and CCAAT boxes are many consensus sequences (LF-A1, LF-B1, TGT3) for liver-specific or -enriched transcription factors (HNF4, HNF1, and HNF5, respectively) and an imperfect direct repeat of thyroid hormone responsive element (TRE), which is located between TGT3 and LF-B1. These sequence motifs are completely conserved among the rat, human, and hamster CYP7 genes. Several modified sterol regulatory element (SRE)-like sequences are located in the upstream flanking region and in the first intron. This highly conserved proximal promoter may play important roles in the transcription activity and in the regulation of the CYP7 gene by physiological agents, such as bile acids and steroid/thyroid hormones. This is the first report describing the complete nucleotide sequence and confirming the structure of a CYP7 gene.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗

n-6 and n-3 fatty acid accumulation in thp-1 cell phospholipids.

The human monocytic leukemia cell line THP-1 is depleted of the long-chain n-6, AA, when compared to human monocytes. This reflects the low availability of this FA in the growth medium generally used for cultured cells. The effects of AA, as well as EPA, supplementation of THP-1 cells on the incorporation of these FA in cell PL, especially in PC and PE, was investigated. In addition the incorporation of labeled AA in PL from THP-1 cells was compared to that in human monocytes. Measurements were done through HPLC separation of PL, detected by UV absorption and radioactivity, FA analysis by GC and characterization of PC subclasses by FAB-MS. Marked differences were observed in the incorporation of the two FA in cell PL, particularly two PC subclasses, and in the accumulation in individual PL after supplementation of THP-1 cells. Accumulation of AA and EPA in THP-1 cells appeared to be mutually independent. The incorporation of AA was also quite different in THP-1 from that in monocytes. Thus, characterization of the FA content in lipids of cultured cells is an essential requirement for optimal utilization of these cells.

Cell Division↗

Release of extracellular matrix components by bovine bone endothelial cells in continuous culture.

Production of collagen type I (pIp), type III (pIIIp), type IV (CIV), type VI (CVI), fibronectin (FN), laminin and glycosaminoglycans (GAGs) has been investigated in a clonal line of Bovine Bone Endothelial (BBE) cells continuously growing in culture. BBE cells produced pIp, pIIIp and FN, whereas they did not synthetize significant amounts of CIV, CVI and laminin. pIp, pIIIp and FN syntheses were influenced by cell density:pIp secretory activity reached its maximum just after cell seeding, whereas pIIIp and FN production increased later, when cells were subconfluent. Furthermore, BBE cells produced and released significant amounts of GAGs into medium.

Animals↗

Activation of apoptosis by serum deprivation in a teratocarcinoma cell line: inhibition by L-acetylcarnitine.

P19 teratoma cells differentiate to neural-like cells in the presence of retinoic acid. If they are plated in N2 synthetic, serum-free medium without being exposed to retinoic acid, they die within 48-72 h. This model has allowed the discovery of the neuron survival-promoting capacity of activin. We have studied the death process triggered by serum removal, and showed that it has the characteristics of apoptosis. In addition we have used this model to study the mechanism of action of L-acetyl-carnitine. This endogenous molecule has been successfully employed as a drug retarding Alzheimer's disease progression. Many pharmacological actions have been reported for this compound. However, so far, it has been difficult to explain the observed results with a single mechanism of action. We have demonstrated that the addition of 100 microM L-acetylcarnitine to the N2 medium, at the time of plating, enhances cell survival, retarding DNA fragmentation and nuclear condensation. We have ruled out the possibility of a role of oxidative stress in the activation of apoptosis, under our conditions. Therefore the protective action of L-acetylcarnitine does not seem to be due to a putative antioxidant activity. Our data, demonstrating a retardation by L-acetylcarnitine of apoptotic cell death, could provide a unifying hypothesis for the explanation of several described actions of this drug. In the view that some of the degenerative diseases in the nervous system could be due to the presence of abnormal stimuli, or the absence of trophic factors that trigger programmed cell death, this model of serum deprivation-induced cell death seems to be relevant for the study of neuroprotective molecules.

Acetylcarnitine↗