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Biomedical subjects

C Battaglia

Publications and source records attributed to C Battaglia.

At least 109 records · Page 6Linked to original sources
PubMed1993

Involvement of RET oncogene in human tumours: specificity of RET activation to thyroid tumours.

Non-thyroid neoplasia were analysed by Southern blot of genomic DNA and DNA prepared by reverse transcription and amplification by polymerase chain reaction (RT/PCR) for the activation of the RET oncogene. It is known that the rearrangement of RET occurs in about 10%-20% of human thyroid papillary carcinomas. None of 528 non-thyroid tumours showed rearrangement of the RET proto-oncogene, whereas three out of 30 thyroid papillary carcinomas were positive for RET activation. Therefore the activation of RET seems to be a somatic cell mutation specific to human thyroid carcinomas.

Base Sequence↗
PubMed1993

Nidogen mediates the formation of ternary complexes of basement membrane components.

Using a recombinant nidogen we have probed the calcium binding potential of various nidogen domains, examined the binding of nidogen to various basement membrane proteins and assessed the ability of nidogen to mediate the formation of ternary complexes between laminin and heparan sulfate proteoglycan and collagen IV and laminin. The results of these experiments indicate that the Ca+2 binding is on the rod-like domain with additional binding observed on the N-terminal G1 domain. With regard to the role of nidogen in mediating complex formation among basement membrane components it was demonstrated that nidogen effectively promotes the formation of a ternary complex between laminin and collagen IV, with both of these components interacting independently with nidogen. Similarly, nidogen mediates a ternary complex formation between laminin and proteoglycan. Interestingly, the interaction between proteoglycan and nidogen is through the protein core of the proteoglycan. We have localized the major interaction sites on nidogen with the proteoglycan core and collagen IV to a region on the globular G2 domain while the C-terminal globe G3 binds to laminin. Ca+2 binding does not appear to be important in either of the binary or ternary complex formations. The data reported allow us to hypothesize that, via the multiple interactions of nidogen with other basement membrane components, nidogen plays a crucial structural role in basement membrane organization and stabilization.

Animals↗
PubMed1993

Left ventricular mass and geometry before and after etiologic treatment in renovascular hypertension, aldosterone-producing adenoma, and pheochromocytoma.

To study left ventricular (LV) geometry in secondary hypertension and its evolution following etiologic treatment, echocardiography was performed in a total of 73 patients: 40 patients with renovascular hypertension (RVH), 21 with aldosterone-producing adenoma (APA), and 12 with pheochromocytoma (PH). Repeat echocardiography was possible in 43 of these patients, 3-24 months following curative renal revascularization or adrenal surgery. Age, sex ratio, and initial drug treatment score were comparable in the three etiologic categories, but 24-h ambulatory blood pressure and LV mass index were significantly higher in APA and RVH than in PH. End-diastolic LV volume was significantly smaller in PH than in APA and RVH. After treatment, the greatest reduction in LV mass occurred in APA (-18%, P < .05) and the lowest in PH (-5%, NS). Both patients with APA and those with PH exhibited a significant decrease in LV wall thickness, whereas LV diameter tended to decrease in APA patients and to increase in PH patients. No significant cardiac changes occurred in RVH patients after treatment. Although LV mass index and ambulatory blood pressure were correlated both before and after treatment, LV mass index changes did not correlate with changes in ambulatory blood pressure or with the known duration of hypertension. Systolic function was normal before and following etiologic treatment in the three categories. These findings suggest that, in addition to blood pressure, volume and/or humoral factors influence the pathogenesis of left ventricular hypertrophy and its reversibility.

Adenoma↗
PubMed1993

Restenosis after a first percutaneous transluminal renal angioplasty.

The incidence of restenosis after a first successful percutaneous transluminal angioplasty of a native renal artery and the clinical and angiographic variables that may influence its occurrence were studied in 104 hypertensive patients. Angiograms obtained immediately before and after angioplasty and, in 92 patients, 8.8 +/- 6.0 months after angioplasty were interpreted separately by two observers. Stenosis severity was classified into five grades, and restenosis was defined by a stenosis one grade or more higher at follow-up than immediately after angioplasty. Interobserver concordance for etiology, stenosis grade, and other angiographic items yielded kappa coefficients in the range of 0.328-0.942. Sessions were organized to reach a consensus in each case. Ostial stenoses were more frequent in patients with atheromatous stenoses, and branch stenoses were more frequent in those with fibromuscular dysplasia. There was no significant difference between the 15 patients (16%) with restenosis and those without concerning sex distribution, mean age, mean blood pressure, plasma creatinine level, and etiology distribution. Truncal stenoses were less prone to restenosis than ostial or branch stenoses (12% versus 35%, respectively; 95% confidence interval of difference, -0.6% to 47%). In patients with atheromatous stenoses, aortitis or aortic ectasia were associated with a high restenosis incidence (35% when present versus 8% when absent; 95% confidence interval of difference, 5% to 48%). In conclusion, restenosis was observed in one sixth of patients after a first successful renal angioplasty; its incidence was low in patients with truncal stenoses and high in those with severe aortic atheroma. Automated renal artery stenosis quantification methods are needed to standardize stenosis description.

Adult↗
PubMed1993

Hypoaldosteronism accompanied by normal or elevated mineralocorticosteroid pathway steroid: a marker of adrenal carcinoma.

In order to find a biochemical marker to assist the physician in the difficult differential diagnosis between malignant and nonmalignant adrenal tumors, plasma levels of the mineralocorticosteroids (deoxycorticosterone, 18-hydroxydeoxycorticosterone, corticosterone, 18-hydroxycorticosterone, and aldosterone) were determined. The same method (RIA which is preceded by a crucial separation step) was used to measure all these steroids including aldosterone. The subjects included 15 adults presenting various clinical signs of adrenocortical tumors (histopathologically: 6 with adrenal carcinoma, 1 with a history of adrenal carcinoma, 1 with adrenal metastasis from other forms of cancer, 6 with adenoma, and 1 with hyperplasia). The results show that both presurgery and during a recurrence of adrenal carcinoma, hypoaldosteronism occurs which contrasts with the normal or even elevated levels of some aldosterone precursors. In the 7 cases of adrenal cortical carcinoma, this dysfunction of the aldosterone pathway was detected regardless of the impairment of the other steroidogenesis pathways, whereas it was never found with a nonmalignant tumor. Despite the limited number of cases so far available, these findings suggest that detection of abnormalities of the aldosterone pathway, and particularly the detection of hypoaldosteronism by an assay method involving a crucial steroid separating step, could contribute to a differential diagnosis between benign and malignant adrenocortical tumor and between adrenal metastasis and other forms of cancer.

18-Hydroxycorticosterone↗
PubMed1993

Short- and long-term effect of angiotensin II receptor blockade in rats with experimental diabetes.

The short- and long-term effects of specific angiotensin II (AII) receptor blockade on the evaluation of glomerular injury in moderately hyperglycemic diabetic rats were studied. Three groups of animals were used, a control group, a group of diabetic rats treated with insulin, and a group of insulin-treated diabetic rats receiving the AII receptor antagonist losartan in drinking water. After 4 to 6 wk of observation, diabetic rats showed higher systolic blood pressure and GFR than normal controls. Losartan treatment prevented both systolic blood pressure and GFR rise. Three other groups of rats, similarly treated for a 1-yr period, were used for renal functional and morphologic evaluation. Diabetic animals had higher urinary protein excretion and glomerulosclerosis incidence than did normal controls. Losartan significantly prevented proteinuria and glomerulosclerosis. Evaluation of the sieving properties of the glomerular membrane by Ficoll fractional clearance showed an important increase in the filtration of this marker in diabetic animals, as compared with that in controls, and almost complete prevention of this change in losartan-treated animals. Theoretical analysis of fractional clearance data with a heteroporous model of glomerular size-selectivity showed that in diabetic animals the size of membrane pores was increased uniformly, as compared with that in controls. These changes were completely prevented by the AII receptor antagonist. The results presented here strongly indicate that reduction of AII activity plays a crucial role in the preservation of glomerular structure and function and suggest that the favorable effects previously observed with angiotensin-converting enzyme inhibition in this model depend directly on the reduction of AII activity.

Angiotensin Receptor Antagonists↗
PubMed1993

Absent or reversed end-diastolic flow in umbilical artery and severe intrauterine growth retardation. An ominous association.

Uteroplacental insufficiency is a major cause of perinatal mortality and postnatal morbidity. Doppler velocimetry has been used to assess well-being of the fetus for several years. In the present study we evaluated the perinatal outcome of growth retarded fetuses with presence or absence of diastolic flow in umbilical artery at Doppler analysis. Forty-six pregnant women with intra-uterine-growth-retardation were studied. Ultrasound assessment of amniotic fluid was performed on alternate days until parturition. A weekly ultrasound measurement of fetal abdominal circumference was done. Doppler analysis of fetal/maternal circulation was performed upon arrival of the patient in hospital and thereafter on alternate days until delivery. Fetal blood was sampled by cordocentesis for immediate blood-gas analysis. In the group (n = 26) with absent or reversed diastolic flow in the umbilical artery, we observed a correspondingly worse blood-gas analysis; a reduced time interposed between the diagnosis and the delivery; a reduced birth weight associated with an increased fetal risk and with a perinatal mortality approaching 60%. Our data suggest that absent or reversed diastolic flow in umbilical artery of growth-retarded fetuses, associated with alterations in other vessels, are ominous signs of serious fetal compromise.

Adult↗
PubMed1993

Mitogenic and dedifferentiating effect of the K-fgf/hst oncogene on rat thyroid PC clone 3 epithelial cells.

Transfection of rat thyroid differentiated epithelial cells, PC clone 3, with the K-fgf/hst oncogene results in alleviation of thyrotropin dependency for growth and suppression of the differentiated phenotype without the acquisition of the fully transformed phenotype. An autocrine mechanism is responsible for these effects, since the proliferation of PC clone 3 cells, induced by K-FGF-conditioned medium, is blocked by anti-K-FGF-specific antibodies. Moreover, addition of K-FGF-conditioned medium inhibits the thyroid differentiated functions. Also, such other members of the fibroblast growth factor family as basic and acidic fibroblast growth factor are able to induce thyroid cell growth and to block expression of the differentiated functions.

Animals↗
PubMed1993

Structural basis of beta 1 integrin-mediated cell adhesion to a large heparan sulfate proteoglycan from basement membranes.

In a cell attachment assay, several cell lines were found to adhere and spread on heparan sulfate proteoglycan purified from a basement membrane-producing tumor. This adhesion was clearly distinct from that on laminin. Cell adhesion to the proteoglycan was completely inhibited by three different antibodies against integrin beta 1 subunit, while inhibitory antibodies against beta 3 and alpha 2 to alpha 6 subunits were without strong effects. Removal of heparan sulfate from the proteoglycan diminished cell attachment, but addition of heparin to the cells did not affect adhesion to the proteoglycan. This suggests that both the heparan sulfate side chains and core protein structures are required for efficient cell adhesion. Studies with proteolytic fragments and synthetic RGD peptides showed that the single RGD sequence of mouse proteoglycan is not involved in cellular recognition. Characterization of fragments also allowed to localize cell adhesion and heparan sulfate attachment sites to the same 160 kDa core protein structure but not to fragments derived from the N-terminal portion of the proteoglycan.

Amino Acid Sequence↗
PubMed1993

The Adenovirus E1A gene blocks the differentiation of a thyroid epithelial cell line, however the neoplastic phenotype is achieved only after cooperation with other oncogenes.

The PC Cl 3 cell line is a well characterized epithelial thyroid cell line of Fischer rat origin. This cell line has the peculiarity of retaining in vitro the typical markers of thyroid differentiation (i.e. thyroglobulin synthesis and secretion, iodide uptake and dependence on TSH for growth). The PC Cl 3 cells have been transfected with the E1A gene of Adenovirus 5. The E1A transfected cells, PC E1A, partially lost the dependency on TSH for growth and completely lost the ability to trap iodide and synthesize thyroglobulin; however they did not acquire the typical markers of the neoplastic phenotype. A highly malignant phenotype was achieved after infection of the PC E1A cells with retroviruses carrying the v-raf, v-abl and polyoma virus middle T oncogenes. In contrast, the PC E1A cells transfected with the E1B gene of Adenovirus were not tumorigenic at all, and those infected with retroviruses carrying oncogenes of the ras family displayed a very weak tumorigenic phenotype.

Adenovirus E1A Proteins↗
PubMed1992

Decision to treat mild hypertension after assessment by ambulatory monitoring and World Health Organisation recommendations.

OBJECTIVE: To determine if one ambulatory blood pressure recording over 12 hours could detect those patients with mild hypertension who needed treatment according to the World Health Organisation-International Society of Hypertension (ISH) guidelines based on the causal measurement of diastolic blood pressure at successive visits to a clinic. DESIGN: Comparison of decision to treat based on one ambulatory measurement over 12 hours and standard blood pressure measurements over six months in the same patients. SETTING: Outpatient hypertension clinic. SUBJECTS: 130 men and women with diastolic blood pressure of 90-104 mm Hg at second visit to clinic. MAIN OUTCOME MEASURES: Blood pressure measurements over six months. Measurement from ambulatory monitoring. Decision to treat. RESULTS: Of the 130 patients included, 108 were followed up over the six months. Treatment was started according to WHO-ISH criteria in 44 (13 at the third visit, 13 at the fourth, 18 at the fifth). According to the selected criteria for ambulatory blood pressure monitoring 41 patients would have been treated. Both methods agreed that the same 27 patients required treatment and the same 50 did not, but they did not agree in 31 patients. When calculated at the optimal diastolic blood pressure threshold determined by a receiver operating characteristic curve, the sensitivity, specificity, and positive predictive value of ambulatory blood pressure monitoring were 71% (95% confidence interval 57% to 84%), 82% (72% to 92%), and 66% (51% to 81%), respectively. CONCLUSION: If the WHO-ISH criteria are accepted as the standard for deciding to treat patients with mild hypertension the predictive value of one ambulatory blood pressure recording over 12 hours is too low to detect with confidence those patients who need treatment when managed according to these criteria.

Blood Pressure Determination↗
PubMed1992

Basement-membrane heparan sulfate proteoglycan binds to laminin by its heparan sulfate chains and to nidogen by sites in the protein core.

A large, low-density form of heparan sulfate proteoglycan was isolated from the Engelbreth-Holm-Swarm (EHS) tumor and demonstrated to bind in immobilized-ligand assays to laminin fragment E3, collagen type IV, fibronectin and nidogen. The first three ligands mainly recognize the heparan sulfate chains, as shown by inhibition with heparin and heparan sulfate and by the failure to bind to the proteoglycan protein core. Nidogen, obtained from the EHS tumor or in recombinant form, binds exclusively to the protein core in a heparin-insensitive manner. Studies with other laminin fragments indicate that the fragment E3 possesses a unique binding site of laminin for the proteoglycan. A major binding site of nidogen was localized to its central globular domain G2 by using overlapping fragments. This allows for the formation of ternary complexes between laminin, nidogen and proteoglycan, suggesting a key role for nidogen in basement-membrane assembly. Evidence is provided for a second proteoglycan-binding site in the C-terminal globule G3 of nidogen, but this interaction prevents the formation of such ternary complexes. Therefore, the G3-mediated nidogen binding to laminin and proteoglycan are mutually exclusive.

Basement Membrane↗
PubMed1992

Cord vessel compression by an expanding allantoic cyst: case report.

The umbilical cord has been inadequately studied by ultrasound. Umbilical cord masses are rare and often misdiagnosed.A case of a 4.3 x 3.2 cm anechoic floating cystic umbilical mass is reported. Doppler examination of the cord proximal to the cyst revealed a high resistance index of 0.84. Twelve hours later the cyst was larger (5.0 x 4.5 cm) and appeared tense; Doppler velocimetry worsened and absence of end-diastolic flow in the umbilical artery was found. Cardiotocography a few hours later showed a bradycardiac non-reactive trace with late decelerations. A live male weighing 1980 g was delivered by Cesarean section. At birth the cord position was normal. Pathological examination showed the lesion to be consistent with an allantoic cyst. This is the first case in which antenatal evidence of cord compression by an expanding allantoic cyst has been demonstrated.

Journal Article↗
PubMed1992

Monoclonal antibodies against laminin A chain fragment E3 and their effects on binding to cells and proteoglycan and on kidney development.

Rat monoclonal antibodies were raised against fragment E3 of the mouse Engelbreth-Holm-Swarm (EHS) tumor laminin and selected according to their exclusive reaction with laminin A chain by immunoblotting and staining pattern in embryonic kidneys by immunofluorescence. Immunochemical studies of nine purified antibodies showed a comparable reaction with unfragmented laminin and fragment E3 but no cross-reaction with several other, unrelated laminin fragments including the major cell-binding fragment E8. Reduction or pepsin digestion of fragment E3 reduced or abolished antibody binding indicating that most of the epitopes involved are conformation dependent and do not include carbohydrates. They are, however, not identical as shown by different reactivities after proteolytic or chemical cleavage of E3. Four of the antibodies were highly active in inhibiting cell adhesion of the teratocarcinoma cell line F9 and the Schwannoma cell line RN22 on fragment E3 (IC50 approximately 1 microgram/ml), while the others were distinctly less active. No inhibition was observed for cell adhesion on unfragmented laminin, consistent with previous findings that this is largely mediated by binding of fragment E8 to alpha 6 beta 1 integrin. A distinct correlation was observed between cell adhesion inhibition and the inhibition of heparansulfate proteoglycan and heparin binding to fragment E3. Since heparin is not very efficient in inhibiting cell adhesion, it indicates that heparin- and cell-binding sites on fragment E3 are in close proximity but not identical. Two of the antibodies also showed partial inhibition of kidney tubule formation in organ culture of embryonic kidney mesenchyme while the other antibodies were inactive. It suggests some but probably minor involvement of the fragment E3 structure of laminin in this developmental process.

Animals↗
PubMed1992

Maternal hyperoxygenation in the treatment of intrauterine growth retardation.

OBJECTIVE: In the current study the efficacy of maternal hyperoxygenation on growth-retarded fetuses was evaluated. STUDY DESIGN: Thirty-six pregnant women with intrauterine growth retardation were studied. The patients were divided in oxygen-treated (n = 17) and untreated (n = 19) groups. Doppler analysis of the fetal circulation was performed on the arrival to the hospital, after 12 hours, and thereafter on alternate days until delivery. Fetal blood was sampled by cordocentesis for immediate blood gas analysis at entrance to the study and the day of delivery. RESULTS: Significant improvement in Doppler flow patterns in treated patients were found when compared with untreated women. The Doppler variations were associated with complementary modifications in fetal blood gas. These differences resulted in a significant modification in perinatal mortality with an incidence of 29% and 68% (p less than 0.01) in treated and untreated groups, respectively. CONCLUSION: Our data suggest a benefit of maternal hyperoxygenation in the treatment of fetal growth retardation.

Arteries↗
PubMed1992

Increased expression of the negative growth factor, galactoside-binding protein, gene in transformed thyroid cells and in human thyroid carcinomas.

Murine beta-galactoside-binding protein has been shown to be a cell growth regulatory molecule and a cytostatic factor. We analysed the beta-galactoside-binding protein gene expression in a thyroid cell system including two normal cell lines (FRTL-5 and PC Cl 3) and the same cells transfected by several oncogenes that induce different degrees of malignancy and differentiation. We show that beta-galactoside-binding protein mRNA levels correlate with the expression of the malignant phenotype. Run-on experiments suggest that a transcriptional effect accounts at least in part for such a difference. We also show that the beta-galactoside-binding protein gene expression is increased in most human papillary thyroid carcinomas compared with normal thyroid.

Adenovirus E1A Proteins↗
PubMed1992

Oral magnesium supplementation improves fetal circulation.

It is well known that pregnancy is a condition in which plasma magnesium falls because of accumulation of the ion in the placenta and fetus. Magnesium (Mg) is therefore widely given as a supplement during pregnancy, particularly in cases of preterm labour. In our experience, the combination of oral Mg (magnesium pyrrolidone carboxylic acid) at a dose of 360 mg/day with conventional ritodrine treatment allows a reduction in ritodrine dosage, accompanied by a significant reduction in side effects. We therefore evaluated changes in fetal blood flow, using pulsed Doppler, in women submitted to combined magnesium and ritodrine treatment compared to those treated with ritodrine plus placebo. The Mg-treated group showed a decrease in vessel resistance both in the umbilical artery and in the fetal middle cerebral artery, indicating that fetal vasculature is sensitive to exogenous Mg. Measurement of plasma and mononuclear cell Mg showed an intracellular increase in the cation of about 10 per cent. We conclude that oral magnesium supplementation in pregnancy is safe and that it has a positive effect on the fetal circulation.

Cerebral Arteries↗