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Biomedical subjects

A Napoli

Publications and source records attributed to A Napoli.

At least 37 records · Page 2Linked to original sources

Survey of the proton affinities of adenine, cytosine, thymine and uracil dideoxyribonucleosides, deoxyribonucleosides and ribonucleosides.

The kinetic method was applied to the determination of the proton affinities (PAs) of modified deoxy- and dideoxyribonucleosides. A correlation between the measured PAs and the replacement of one of the three hydroxyl groups of the ribose unit is presented. A PA scale was obtained which shows that the replacement of the primary or of one or both secondary hydroxyl groups of a ribonucleoside with a hydrogen atom induces the lowering or the enhancement of the nucleoside PA, respectively. The scale extends over a very narrow range of approximately 2 kcal mol(-1), thus demonstrating the sensitivity of the kinetic method in the evaluation of small differences in thermodynamic parameters.

Adenine Nucleotides↗

Fetal pancreatic function in infants of diabetic and rhesus-isoimmunized women.

OBJECTIVE: To measure insulin and glucagon concentrations in amniotic fluid (AF) collected near term in basal conditions and after an arginine test in diabetic, rhesus-isoimmunized, and control pregnant women. METHODS: At baseline, AF was collected from 44 diabetic, 32 rhesus-isoimmunized, and 27 control pregnant women in late pregnancy. Fifty-two diabetic, six rhesus-isoimmunized, and nine control pregnant women had amniocentesis 2 hours after arginine infusion (30 g intravenous/30 minutes) at 33-36 weeks. RESULTS: Baseline AF glucose concentrations were significantly greater in diabetic women than the other conditions, and they related to the gestational age in the women with hemolytic disease of the newborn. Insulin and glucagon AF content of isoimmunized pregnancies overlapped controls, whereas insulin and insulin/glucagon molar ratios were significantly higher, and glucagon values lower, in diabetic pregnancies compared with isoimmunized and control pregnancies. In isoimmunized pregnancies, the AF concentrations of glucose, insulin, and glucagon were correlated with gestational age (less than 34, 34 weeks or more). The samples collected after arginine infusion, compared with those collected at baseline, showed significantly greater insulin and insulin/glucagon molar ratio values in diabetic (28 +/- 5 versus 11 +/- 1 microU/mL, P = .001; 29.4 +/- 1.7 versus 12.0 +/- 2.8, P = .001) and in Rh pregnant women (18 +/- 6 versus 7.7 +/- 0.7 microU/mL, P = .001; 30 +/- 9 versus 3.4 +/- 0.4 I/G, P = .001), whereas no significant difference was observed in the controls. CONCLUSION: Basal islet hormone concentrations in AF are modified by maternal diabetes and further influenced by arginine administration. Arginine produces an AF response that is similar in pregnancies complicated by diabetes mellitus and rhesus-isoimmunization, despite different (hyperglycemia and euglycemia) maternal blood glucose levels.

Adult↗

Cellular heterogeneity of granular cell tumours: a clue to their nature?

Most granular cell tumours (GCTs) are benign proliferations of purported Schwannian derivation, showing immunoreactivity for Schwann cell-related antigens. Due to incomplete agreement on the precise nature of GCTs (reactive vs neoplastic), we performed an immunohistochemical study with the alkaline phosphatase/anti-alkaline phosphatase (APAAP) technique on 30 GCTs. The aim was to evaluate their growth patterns and the possible relationships of granular cells with other nerve sheath-related cell types (i.e., Schwann and perineurial cells, and dendritic cells displaying CD34/vimentin immunoreactivity). An expansive growth pattern was detected in five cases, a pseudoinfiltrative growth pattern in nine cases and a mixture of the above in the remaining 16 cases. Besides immunoreactivity for S-100 protein, neuron-specific enolase, vimentin, CD57, CD68, MAC 387, alpha-1-antitrypsin and alpha-1-antichymotrypsin in granular cells, we documented intimate architectural relationships between granular cells, Schwann and perineurial cells, and a third type of CD34/vimentin-positive nerve sheath-related cell in most GCTs. These results suggest that GCTs are heterogeneous lesions. Some of them show a pseudoinfiltrative growth pattern and retain close relationships with the normal components of the nerve sheath. In other lesions, granular cells grow in an expansive fashion and constitute the predominant cell component of the tumour. These architectural and immunophenotypic differences may reflect a different nature of GCTs: they may initially represent reactive or hamartomatous lesions that subsequently acquire truly neoplastic potential.

Adult↗

Insulin-like growth factor-I expression in normal and diseased endometrium.

While the role of steroid hormones in the regulation of endometrial proliferation and differentiation is well established, the effects of growth factors and their receptors in normal and neoplastic endometrium remain a matter of debate. Previous studies have documented the positive effects of insulin-like growth factor-I (IGF-I) on epithelial cell proliferation and the active production of this growth factor in endometrial tissues. In view of decreased expression of transforming growth factor-beta1 (TGF-beta1), an antagonist of IGF-I, in endometrial carcinoma, we investigated the expression of IGF-I, at both the mRNA and protein levels, and the immunoreactivity for type I IGF-I receptor in 30 formalin-fixed, paraffin-embedded tissue samples of normal and neoplastic endometrium, in order to possibly clarify the role of IGF-I in endometrial proliferation and differentiation. Our results demonstrate a reduced expression of IGF-I mRNA in endometrial carcinomas compared with non-neoplastic tissues, despite equivalent immunohistochemical expression of IGF-I and IGF-I receptor. Our data suggest that IGF-I and its corresponding receptor may not be directly involved in endometrial cancer cell proliferation and differentiation in vivo, though other components of the IGF-I system (e.g., IGF binding proteins) may affect endometrial malignant transformation and tumor progression.

Adult↗

An Lrp-like protein of the hyperthermophilic archaeon Sulfolobus solfataricus which binds to its own promoter.

Regulation of gene expression in the domain Archaea, and specifically hyperthermophiles, has been poorly investigated so far. Biochemical experiments and genome sequencing have shown that, despite the prokaryotic cell and genome organization, basal transcriptional elements of members of the domain Archaea (i.e., TATA box-like sequences, RNA polymerase, and transcription factors TBP, TFIIB, and TFIIS) are of the eukaryotic type. However, open reading frames potentially coding for bacterium-type transcription regulation factors have been recognized in different archaeal strains. This finding raises the question of how bacterial and eukaryotic elements interact in regulating gene expression in Archaea. We have identified a gene coding for a bacterium-type transcription factor in the hyperthermophilic archaeon Sulfolobus solfataricus. The protein, named Lrs14, contains a potential helix-turn-helix motif and is related to the Lrp-AsnC family of regulators of gene expression in the class Bacteria. We show that Lrs14, expressed in Escherichia coli, is a highly thermostable DNA-binding protein. Bandshift and DNase I footprint analyses show that Lrs14 specifically binds to multiple sequences in its own promoter and that the region of binding overlaps the TATA box, suggesting that, like the E. coli Lrp, Lrs14 is autoregulated. We also show that the lrs14 transcript is accumulated in the late growth stages of S. solfataricus.

Amino Acid Sequence↗

Localization of pancreatic insulinomas with MR imaging at 0.5 T.

OBJECTIVE: To determine the role of MR imaging in the localization of pancreatic insulinomas in patients with clinical and laboratory diagnosis of insulin-producing tumor. MATERIAL AND METHODS: Thirty-one patients presenting with signs and symptoms of pancreatic insulinomas were prospectively included in our study. Twenty-six patients underwent surgery, and pathologic specimens were examined: 5 patients, in whom the initial diagnosis of insulinoma was excluded, were also studied and then followed up. All patients were studied with a high gradient power 0.5 T magnet. Images were evaluated by 2 radiologists blinded to previous investigations, tests and results. RESULTS: MR imaging correctly localized 24 of the 26 insulinomas (2 were false-negative and 1 false-positive) and was correctly negative in the 5 control patients. The interobserver agreement had a kappa value of 0.89. CONCLUSION: MR imaging was accurate in localizing pancreatic insulinomas and as a consequence, patients in our institution are now submitted to surgery directly after the MR examination. Invasive methods are considered only in cases in which, despite clear biochemical results, MR imaging has not demonstrated a pancreatic focal lesion.

Adolescent↗

Down-regulated expression of transforming growth factor beta 1 mRNA in endometrial carcinoma.

Transforming growth factor beta1 (TGF-beta1) is a potent modulator of cell proliferation in vitro, and recent studies have demonstrated its overexpression in several different tumours; nevertheless, the molecular mechanisms of TGF-beta1 action on cell growth and differentiation have not been fully elucidated. To clarify the role of TGF-beta and its receptor in human endometrial proliferation and differentiation, TGF-beta1 expression at both the mRNA and protein levels has been evaluated by using Northern blotting and immunohistochemistry, in both normal (atrophic, proliferative and secretory) and neoplastic (adenocarcinoma) endometrial samples. This study demonstrates that TGF-beta1 mRNA expression is dramatically reduced in endometrial carcinomas with respect to non-neoplastic tissues, whereas the immunohistochemical expression of TGF-beta1 is enhanced in the epithelial component of endometrial carcinomas compared with non-neoplastic tissues. These data suggest that TGF-beta1 acts as a paracrine regulator of endometrial cell proliferation and that it may contribute to the carcinogenic mechanisms of endometrial carcinoma.

Activin Receptors, Type I↗

Annealing of complementary DNA strands above the melting point of the duplex promoted by an archaeal protein.

One enigma in the biology of hyperthermophilic microorganisms, living near or above 100 degrees C, is how their genomes can be stable and, at the same time, plastic at temperatures above the melting point. The nonspecific DNA-binding protein Sso7d of the hyperthermophilic archaeon Sulfolobus solfataricus is known to protect DNA from thermal denaturation. We report here that Sso7d promotes the renaturation of complementary DNA strands at temperatures above the melting point of the duplex. This novel annealing activity is strictly homology-dependent, and even one mismatch in a stretch of 17 complementary bases severely reduces its efficiency. Since pairing of homologous single strands is a key step in all fundamental processes involving nucleic acids, such as transcription, replication, recombination, and repair, Sso7d is a candidate component of the protein machinery devoted to the coupling of DNA stability to metabolic flexibility at high temperature.

Archaeal Proteins↗

Blood pressure monitoring in diabetic pregnancy.

Hypertensive disorders which complicate 5-10% of all pregnancies are more frequent in diabetic women. We longitudinally monitored blood pressure (BP) for a 24 h period in 54 diabetic out patients, at each trimester of pregnancy, in order to observe the relationship between the blood pressure behaviour and the main clinical features of these subjects. A relationship was found between blood pressure and the diabetes type. In insulin-dependent diabetes mellitus (IDDM) women, the age of diagnosis and the diabetes duration played the major role whereas, in non insulin-dependent diabetes mellitus (NIDDM) women only the patients' age was correlated with the BP levels. Higher BP levels were found in women belonging to the White class D, and whose diabetes duration was more than 10 years. An interesting correlation was also demonstrated between BP and insulin requirement, in late pregnancy as well as the time of delivery. Early in pregnancy, BP levels, even if within normal range, were undoubtedly higher in those women who developed hypertension compared to those who continued to be normotensive. Daytime BP values were always found higher than night-time BP values but, the physiological biorhythm seemed to be altered at the end of pregnancy.

Adolescent↗

Diabetes and pregnancy: prophylaxis of genital infections.

Diabetic pregnant women have many potential reasons to have genital infections such as poor metabolic control and impairement of leucocyte function. Relative immune deficiency exists in pregnancy. This study was designed to test the hypotheses that pregnant patients with insulin-dependent diabetes have a higher rate of ante partum genital infections when compared with a pair-matched control population. Two groups of pregnant women consisting of 23 patients with and 23 without diabetes mellitus, underwent colposcopy and cytology between 16th and 24th week of gestation to detect the presence of human papilloma virus (HPV), Gardnerella vaginalis, Candida albicans and aspecific infections. No significant differences were observed between the two groups.

Adult↗

Telemedicine in the treatment of diabetic pregnancy.

Good diabetic control requires that treatment be continuously adapted to the patient behavior. We investigated whether the use of telemedicine could present an advantage to the management of the diabetic woman during pregnancy. A system completely automatic (DIANET system) was used. Twenty IDDM women participated in the study: 10 treated by telemedicine and 10 by conventional system, at times "entry" (9.5 weeks), "basal" (9.5-16.8 weeks), "1st month" of investigation, and "end" (near delivery). All women used intensified protocols of insulin administration. The treatment with DIANET vs conventional showed a better metabolic control as estimated by profile of blood glucose absolute values (at time "end": values significantly lower before breakfast: 87 +/- 6 vs 104 +/- 4 mg, lunch: 85 +/- 5 vs 104 +/- 4 mg, and after dinner: 102 +/- 5 vs 124 +/- 6 mg). These results were associated with higher insulin doses in the DIANET vs conventional treatment, and a significant reduction of hypoglycemic reaction in both group. Our results suggest that telemedicine-DIANET is a practical way of providing specialist care in the pregnancy area.

Adult↗

IGF-1 levels in diabetic pregnant women and their infants.

Plasma IGF-1 was measured in 38 diabetic pregnant women (DPW) and in 12 non diabetic pregnant women (NDPW) during the 1st, 2nd and 3rd trimester of pregnancy. IGF-1 was measured in the cord blood of 24 infants of diabetic mothers (IDDM) and IGF-1 in 11 infants of non diabetic mothers (NIDDM). A progressive and significant (p < 0.0001) increase of IGF-1 values was found throughout the pregnancy both in DPW and NDPW IGF-1 (149 +/- 18 ng/ml vs 181 +/- 14 ng/ml, 184 +/- 17 ng/ml vs 232 +/- 25 ng/ml, 279 +/- 20 ng/ml vs 325 +/- 17 ng/ml). Furthermore IGF-1 decreased significantly soon after delivery in both groups of women. In type 1 diabetic pregnant women IGF-1 values were significantly lower than the controlled non diabetic patients. IGF-1 in the cord blood was significantly higher in IDDM than in NIDDM 86 +/- 7 ng/ml and 62 +/- 7 ng/ml respectively (p < 0.03). In addition, DPW plasma levels IGF-1 were positively correlated with the weight of the placenta (r = 0.233, p < 0.03) and negatively correlated with the diabetes duration (r = 0.412, p < 0.05). No correlations were found between IGF-1 cord blood concentrations and gestational age, birth weight and length, but there was a significant correlation with weight percentile (r = 0.846, p < 0.001). No correlation was found between maternal IGF-1 plasma levels and other parameters like insulin need, weight gain, metabolic control and time of delivery.

Adult↗

Autoimmune markers of diabetes in diabetic pregnancy.

Gestational diabetes mellitus (GDM) has been described in 1-3% of pregnancies and increases the risk (up to 60-70%) to subsequently developing an overt diabetes (generally of type 2 non insulin-dependent diabetes mellitus (NIDDM)). Several humoral autoimmune phenomena have been described in GDM: islet cell antibodies (ICA) have been found and it was shown that ICA+ patients tend to have a worse glucose tolerance. Recently, autoantibodies against glutamic acid decarboxylase (GAD), were detected in type 1 diabetic sera before or at the onset of the disease; these markers, as well as ICA and insulin antibodies, seem to have a predictive value for the onset of the disease. Aim of our study was to investigate the presence of GAD65 in 83 GDM, 79 NIDDM and 64 pregnant normal women in late gestation. GAD Ab positivity was found (0.035 index as limit) only in GDM and NIDDM (3.6% in GDM, 3.8% in NIDDM, and nothing in control women). These results indicate that GAD positivity in GDM overlaps that of NIDDM, suggesting that the two diabetic populations have the same predisposition to develop a type 1 diabetes mellitus, and likely they share the same disease. Further studies need to clarify whether this prevalence of GAD positivity may unmask type 1 diabetes in both GDM and NIDDM diabetic women.

Adult↗

Amniotic fluid insulin and C peptide levels in diabetic and nondiabetic women during early pregnancy.

Thanks to the widespread use of amniocentesis, glucose, insulin, and C peptide have often been measured in amniotic fluid (AF) during late gestation, but little is known about their concentrations during early pregnancy. To better understand early fetal beta-cell function under normal conditions and in the presence of maternal diabetes, we measured glucose, insulin, and C peptide in the AF collected during weeks 15-22 in 77 healthy and 9 diabetic women undergoing amniocentesis for clinical indications and compared the results with those obtained during late pregnancy (weeks 34-36). The AF C peptide concentration was higher in diabetic women (102 +/- 53 vs. 38 +/- 2 pmol/L), in the women with a family history of diabetes (41 +/- 6 vs. 35 +/- 2 pmol/L), after the 19th week of gestation (46 +/- 5 vs. 35 +/- 2 pmol/L; in the presence of lower glucose concentrations), and in the presence of maternal plasma glucose levels greater than 5.56 mmol/L (42 +/- 3.5 vs. 34 +/- 2 pmol/L). The comparison between early and late gestation showed decreasing glucose and increasing C peptide concentrations in both healthy and diabetic women (in the latter, C peptide values were always 3 times higher), whereas the insulin concentration was increased in late gestation only in diabetic women. The AF C peptide/insulin molar ratio increased throughout pregnancy in both healthy (from 0.97 +/- 0.06 to 4.3 +/- 1.2) and diabetic (from 2.9 +/- 1.1 to 13.2 +/- 1.6) women. These parallel changes suggest that the fetal clearance and/or degradation of insulin and C peptide may greatly change during both normal and diabetic gestation.

Adult↗

Relevance of postprandial glycosuria in survey for diabetes mellitus.

Since the oral glucose tolerance test is not applicable in large surveys for diabetes mellitus, economic tests or clinical criteria are required to select subjects needing a complete glycometabolic assessment. This study evaluated, in a selected high risk population (110 subjects; 71 males; median age: 53 years, range 30-70), the utility of glycosuria after a meal rich in carbohydrates in the detecting of diabetes, compared to other tests for glycosuria (fasting glycosuria, glycosuria after a glucose load) and clinical criteria (diabetic family history, overweight and their combination). For each test and, retrospectively, for clinical criteria, sensitivity, sensibility, predictive value positive (PVP) and predictive value negative (PVN) were calculated. Postprandial glycosuria resulted to be an effective approach (sensitivity: 100%; specificity: 44%; PVP: 23%, PVN: 100%) in people over 50 years old, in which both clinical criteria (sensitivity: 22-78%; PVN: 81-90%) and fasting glycosuria (sensitivity 11%; PVN: 86%) proved defective. In younger subjects both the presence of fasting glycosuria (sensitivity: 100%; specificity: 96%; PVP: 33%; PVN: 100%) and of relevant diabetic family history (sensitivity: 100%; specificity: 85%; PVN: 100%) proved more adequate as screening procedures.

Adult↗

[Acute hepatotoxicity from amiodarone].

The functional and histological liver alterations induced by amiodarone treatment have been well known for some time and often consist in isolated increases in transaminase levels during long-term treatment. Secondary phospholipidosis was observed in these cases, an alteration which suggests the presence of toxic damage. Reports in the literature also indicate acute liver intoxication, including a number of fatal cases. This paper reports the finding of acute alterations of laboratory parameters indicative of hepatocytonecrosis with alterations of protein synthesis capacity following the first dose of the drug and which regressed after its suspension. On the basis of a review of the literature the authors propose that, in addition to a dose-dependent toxic mechanism, immunogenic or idiosyncratic mechanisms may also play a role in the onset and manifestation of acute liver intoxication by amiodarone.

Acute Disease↗