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Biomedical subjects

D Ferrara

Publications and source records attributed to D Ferrara.

At least 37 records · Page 2Linked to original sources

Recombinant human thyroid stimulating hormone: development of a biotechnology product for detection of metastatic lesions of thyroid carcinoma.

We have genetically engineered a cell line, and developed a reproducible process, for the expression and purification of biologically active recombinant human thyroid stimulating hormone (rhTSH).rhTSH was expressed by co-transfecting a human alpha-subunit cDNA with a human beta-subunit partial genomic clone into Chinese Hamster Ovary (CHO) cells. Stable transfectants which expressed high levels of rhTSH were selected, and subsequently cultured on microcarrier beads. The rhTSH-containing media, produced under serum-free conditions, was clarified and purified by a combination of ion exchange, dye and gel filtration chromatographies. Individual step recoveries were greater than 90% with the exception of a very conservative pooling of the final gel filtration step (78% recovery) that resulted in a cumulative yield of 54% for the purification process. Purity of the final bulk material was judged to be > 99% by SDS polyacrylamide gel electrophoresis (SDS-PAGE), reverse phase HPLC, and size exclusion chromatography. Initial characterization of the oligosaccharide composition indicated the presence of partially sialylated bi- and triantenary complex oligosaccharides. Purified rhTSH was active in a thyroid membrane bioactivity assay with a specific activity of 8.2 IU/mg. The in vivo activity of rhTSH in cynomolgus monkeys appeared to be equal to or greater than that reported for bovine TSH (bTSH) in human subjects. The rapid clearance phase half-life of rhTSH was approximately 35 minutes while the post-distribution phase half life was approximately 9.8 hours. Furthermore, the monkeys showed cumulative increases in minimum plasma rhTSH levels when given three daily intramuscular (IM) rhTSH injections; a phenomenon not observed when bTSH had been administered to humans. The rhTSH showed no evidence of toxic or adverse effects when administered at doses up to 7.2 IU/kg and 0.52 IU/kg in rat and monkey, respectively. These are 50X and 4X multiples of the bTSH doses of 0.143 IU/kg (10 IU/70kg) previously administered to humans.

Amino Acid Sequence↗

[Use of enoximone in the postoperative course of heart surgery].

The aim of this study was to evaluate the efficacy and safety of enoximone, an imidazolonic compound inhibiting cardiac phosphodiesterase III, during the postoperative period. The drug was administered prior to the usual stages of weaning the patient off extracorporeal circulation, to a group of 20 subjects who presented an ejection fraction of less than 35% following hemodynamic studies. Patients were randomly subdivided into 4 groups each of which received a different dose of enoximone according to the following protocol: Group A, 1 mg/kg bolus and slow infusion at 10 gamma/kg/min; Group B, 0.5 mg/kg bolus and slow infusion at 15 gamma/kg/min; Group C, 0.5 mg/kg bolus and slow infusion at 10 gamma/kg/min; Group D, slow infusion at 10 gamma/kg/min. The best results in hemodynamic terms and with regard to the positive inotropic and vasodilatory action of the drug in question were obtained in Group C. Increased cardiac output was observed in all patients within 120 minutes of enoximone administration and reduced systemic vascular resistance after approximately 6 hours of infusion. Special attention should be drawn to the use of the drug in patients who do not respond to conventional therapy due to its mechanism of action which is not dependent on beta receptors, thus enabling good results to be achieved even when these are down regulated. Special care must be taken however in administrating enoximone to platelet-deficient patients since the reduction of platelet levels is one of its collateral effect. Other collateral effects observed were: supraventricular arrhythmias and ventricular tachyarrhythmias.

Cardiac Output↗

A family of type I keratin genes and the homeobox-2 gene complex are closely linked to the rex locus on mouse chromosome 11.

Type I and type II keratins are major constituents of intermediate filaments that play a fundamental role in the cytoskeletal network. By using both somatic cell hybrids and conventional and interspecific linkage crosses, several genes encoding type I keratins, including the epidermal keratin K10, were shown to be closely linked to the homeobox-2 complex and the rex locus on mouse chromosome 11. The absence of crossovers between type I keratin-encoding genes and rex (N = 239), a locus affecting hair development, raises the possibility that mutations at rex and neighboring loci affecting skin and hair development involve type I keratin genes.

Alleles↗

Metabolic effects of moderate alcohol intake with meals in insulin-dependent diabetics controlled by artificial endocrine pancreas (AEP) and in normal subjects.

In order to evaluate the effects of moderate alcohol intake on intermediate metabolites, five normal subjects and five euglycemic insulin-dependent diabetics (IDDM) were administered two different isocaloric diets; in one diet 35% of the caloric intake consisted of red wine. The insulin-dependent diabetics were connected to an artificial endocrine pancreas (AEP), and glucose levels were continuously monitored. Blood lactate, pyruvate, acetoacetate (AcAc), 3-hydroxybutyrate (3-OHB), glycerol, free fatty acids (FFA), and alanine levels were measured over a 15-hour period from 9 AM to 12 PM. The results showed that alcohol intake did not significantly influence the glucose profiles in either group (111 +/- 4 mg/100 ml versus 110 +/- 4 mg/100 ml for IDDM; 72 +/- 2 mg/100 ml versus 82 +/- 3 mg/100 ml for controls, 15-hour mean +/- SEM), but in both groups it induced a marked increased in the levels of lactate (1.115 +/- 0.067 mM/liter with alcohol versus 0.706 +/- 0.031 mM/liter without alcohol for IDDM; 0.847 +/- 0.052 mM/liter with alcohol versus 0.666 +/- 0.035 mM/liter without alcohol for controls), in the lactate/pyruvate ratio (24.04 +/- 2.12 with alcohol versus 11.42 +/- 0.20 without alcohol for IDDM; 20.84 +/- 2.16 with alcohol versus 11.62 +/- 0.27 without alcohol for controls), in the levels of 3-OHB (0.081 +/- 0.007 mM/liter with alcohol versus 0.046 +/- 0.003 mM/liter without alcohol for IDDM; 0.067 +/- 0.007 mM/liter with alcohol versus 0.025 +/- 0.002 mM/liter without alcohol for controls) and in the 3-OHB/AcAc ratio (1.452 +/- 0.153 with alcohol versus 0.599 +/- 0.036 without alcohol for IDDM; 1.723 +/- 0.198 with alcohol versus 0.439 +/- 0.040 without alcohol for controls) because of a more reduced redox state. Alcohol intake during meals depressed alanine concentration, while glycerol levels showed a transient increase. Reduced blood FFA concentrations after alcohol intake were observed only in controls. This study demonstrates that moderate alcohol intake with meals also affects intermediate metabolites despite euglycemia. These effects were similar both in normal subjects and in IDDM, even if the harmful effects of alcohol may be enhanced by poor metabolic control in the latter.

Adult↗

[The artificial pancreas in the evaluation of insulin sensitivity in healthy subjects].

24-hours peripheral insulin sensitivity was studied in 5 healthy subjects by mean of artificial pancreas (Biostator), using the glycemic clamp technique (100 mg%). A sharp rise of insulin sensitivity (expressed as glucose required/insulin evoked ratio) was obtained in the morning, confirming our previous data observed by insulin tolerance test, but in a more physiological condition. The subjects appeared well synchronized as documented by statistically significant circadian rhythms in both serum cortisol and body temperature.

Adult↗

A brush fire forensic case.

In Italy, every summer forest fires attract public attention due to the number of victims, the intensity of the fires, the areas devastated, the environmental damage and the loss of property. Excluding some fires by natural causes, other causes are related to the social, economic, and productive profile of the territory. The erroneous expectation is that wooded areas destroyed by fire can then be used for private interests. Often, a fire, started to clear a small area, can completely change the expected result, producing disaster, loss of property, destruction of entire forests and resident fauna, and kill innocent people. In this case report, the reconstruction of an arson scene, the analytical techniques and the results obtained are illustrated in this paper, with the aim of sharing with other research laboratories the current knowledge on forest fire.

Firesetting Behavior↗

[Vaginal infections in a population of diabetic children and adolescents].

The prevalence of vaginal infections has been evaluated in 51 patient affected by insulin-dependent diabetes (IDDM) and in a control group of girls matched for age. Most frequent infectious agents were Candida Albicans (42.8%) and Streptococcus B (28.5%). No statistical significant relationship was observed between infection and duration of diabetes nor metabolic control, while the relationship was positive between infection and puberty. The peculiarity of this infection during IDDM is stressed and the difficulties in the infection when caused by Streptococcus B are discussed.

Adolescent↗