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Biomedical subjects

A Rossi

Publications and source records attributed to A Rossi.

15 recordsLinked to original sources

CRISPR/Cpf1-mediated knockout of FLG in human induced pluripotent stem cells generates a model for studying epidermal barrier dysfunction.

Loss of filaggrin (FLG) function impairs skin barrier formation and contributes to common inflammatory skin diseases. In this study, we established a FLG knockout human induced pluripotent stem cell (iPSC) line based on KOLF2.1 J using CRISPR/Cas12a (Cpf1)-mediated genome editing. A guide RNA targeting exon 2 introduced a homozygous mutation, which was confirmed by sequencing. The edited cells maintained typical pluripotent stem cell morphology, expressed key undifferentiated markers, and retained the ability to differentiate into all three germ layers. Karyotype and copy number variation (CNV) analyses confirmed genomic stability and parental origin; the cells were free of mycoplasma. This cell line enables studies of FLG-associated skin biology and pathology.

Humans

[Effect of an adrenergic-parasympatholytic aerosol combination on the respiratory function].

The ventilatory and cardiocirculatory effects of salbutamol-ipratropium aerosol were examined in 27 subjects with bronchial obstruction. The activity of the association was compared with that of the two components at therapeutic doses. Then the effects and possible side-effects of the association were assessed at increasing doses. Lastly, the association was compared with its components. The association had the same latency time, but a more prolonged effect (still effective after 120'), when compared with salbutamol. It was decidedly superior to the parasympatholytic. No side-effects of any kind were observed.

Aerosols

[Systolic time intervals in essential hypertension. I. Study of untreated patients].

15 patients with Stage II (VHO Classification) hypertension were studied before treatment. The following systolic time intervals were measured: 1) total electromechanical systolic period (QS2); 2) left ventricular ejection time (LVET); 3) interval between the first and second sounds (S1 S2); 4) pre-ejection period (PEP); 5) interval between the start of QRS and the first sound (QS1); 6) isovolumetric contraction time (ICT); 7) PEP/LVET ratio. The values measured were compared to the theoretical values obtained by the Weissler regression methods, taking into consideration the sex of the patient and the heart rate. QS1 and the ICT were both a slightly longer than normal; the PEP was increased by 25.6% (26.8 ms), whilst the LVET was decreased by 7.9% (24.0 ms), both differences being significant; QS2 increased by 1.1% (to 4.9 ms) but this was not significant; the PEP/LVET ratio was 0.479 +/- 0.12. These results seem to characterise moderate systemic hypertension with a significant relation between the variations of PEP, LVET and PEP/LVET with the diastolic blood pressure; although they have no absolute value, these results may be used in a longitudinal study to follow the course of hypertension and to study the effects of treatment.

Adult

[Systolic time intervals in essential hypertension. II. Variations produced by treatment with labetalol].

Characteristic changes in the systolic time intervals in Stage II (WHO Classification) hypertension have been demonstrated comprising an increase in the pre ejection period (PEP), a decrease in the left ventricular ejection time (LVET) both statistically significant, and an increase in the PEP/LVET ratio. We have studied the variations brought about by effective hypotensive therapy with an alpha and beta blocking agent (Labetalol) in 15 patients over a period of 90 days, with an average dosage of 420 mg/day in three divided doses. There was no significant variations in the PEP, but the LVET which had been reduced by 7.9% returned to within 2.8% of normal, with a reduction in the PEP/LVET ratio. The variations of these systolic indices (generally considered to be the most sensitive assessment of left ventricular function) seem to show that the hypotensive effect of labetalol is not related to a reduction in cardiac efficiency.

Adult

Clinical pharmacology of a combination of bronchodilators.

27 hospitalized patients (15 suffering from chronic bronchitis with evident bronchospasm and 12 with extrinsic asthma) were evaluated with regard to the bronchodilating effects of a Salbutamol + Ipratropium Bromide combination administered by aerosol. For comparison, the bronchial spasmolytic effectiveness of both drugs administered separately at therapeutic doses was also evaluated. Subsequently, the activity of increasing doses of the combination was studied, with particular regard to possible side-effects. The pharmacological combination studied exerted a strong bronchodilating activity, independently of dose increase, both in asthmatic and in bronchitic patients. No side-effects were observed.

Aerosols

[Kinetics of alpha phosphate turnover in the free nucleotides of isolated rabbit hearts during the incorporation of adenosine or uridine].

The isolated rabbit heart was perfused with tritium-labelled adenosine or uridine at constant concentration (respectively 10 and 2 micrometer) and specific activity. The transfer rates of the precursors into free nucleotides were obtained by calculating the uptake of isotope into the products. The rates of phosphorylation of the nucleotides were estimated by following the incorporation of 32PO4 3- into the alpha phosphate groups. The results obtained with the two isotopes show that the rate of labelling of the alpha phosphate groups is a good estimate of the turnover of nucleotides when the mechanism of synthesis involves phosphorylation of a riboside.

Adenine Nucleotides

[Turnover of free adenine nucleotides of the isolated and perfused rabbit heart].

The turnover of free adenine nucleotides was studied in the perfused rabbit heart by the decline in radioactivity 3 h 30 after administration of a single pulse of tritiated adenine. The radioactivity of the perfusate was followed during the experiments. About 7% of the labelled adenine nucleotides were renewed by hour and 1,5% of the radioactivity was lossed by hour in the perfusion fluid.

Adenine Nucleotides

Yeast hexokinase A. Succinylation and properties of the active subunit.

Yeast hexokinase A (ATP:D-hexose 6-phosphotransferase, EC2.7.1.1) dissociates into its subunits upon reaction with succinic anhydride. The chemically modified subunits could be isolated in a catalytically active form. The Km values found for ATP and for glucose were of the some order as those found for the native enzyme. Of the 37 amino groups present per enzyme subunit, 2-3 of these groups might be located in the proximity of the region of subunit interactions. The 50% loss of the initial activity, which follows the succinylation of these more reactive amino groups, does not seem to be due to the modification of a residue on the enzyme active site or to a change of the tertiary structure of the protein. This 50%loss of the enzyme activity may be related to the dissociation of the dimer into monomers. Both native enzyme and the succinylated subunits have the same H-dependent denaturation rate profiles in response to 2 M urea. Moreover, the apparent pK of the group involved in the transition from a more stable conformation of the protein in the acid range to a less stable one at alkaline pH seems to be similar to the pK of the group implicated in the transition between the protonated inactive form of the enzyme and an active deprotonated form. The succinylated subunit presents 'negative co-operativity' with respect to ATP at slightly acid pH; however, the burst-type slow transient in the reaction progress curve and the activation effect induced by physiological polyanions, effects observed for the native enzyme, were not detected in the standard experimental conditions with the succinylated subunit.

Acylation