Search PubMed⌕ Search

Biomedical subjects

R Franco

Publications and source records attributed to R Franco.

At least 145 records · Page 8Linked to original sources
PubMed1991

The C. elegans unc-104 gene encodes a putative kinesin heavy chain-like protein.

Mutations in the unc-104 gene of the nematode C. elegans result in uncoordinated and slow movement. Transposon insertions in three unc-104 alleles (e2184, rh1016, and rh1017) were used as physical markers to clone the unc-104 gene. DNA sequence analysis of unc-104 cDNAs revealed an open reading frame capable of encoding a 1584 amino acid protein with similarities to kinesin heavy chain. The similarities are greatest in the amino-terminal ATPase and microtubule-binding domains. Although the primary sequence relatedness to kinesin is weak in the remainder of the molecule, the predicted secondary structure and regional isoelectric points are similar to kinesin heavy chain.

Adenosine Triphosphatases↗
PubMed1991

Adenosine receptors in myelin fractions and subfractions: the effect of the agonist (R)-phenylisopropyladenosine on myelin membrane microviscosity.

In this article the existence of A1 adenosine receptors and the absence of A2 adenosine receptors in myelin membranes purified from pig brain white matter are demonstrated. The characterization of (R)-[3H]phenylisopropyladenosine ([3H]R-PIA) binding to purified myelin fractions was performed. The distribution of high- and low-affinity species of the A1 adenosine receptor was different in heavy, medium, and light myelin. The fluidity of myelin subfractions and of pig brain cortical membranes was estimated; the microviscosity of heavy myelin (5.4 poises) and of cortical membranes (5.1 poises) was similar and less than that of medium (7.8 poises) and light (8.2 poises) myelin. It was also demonstrated that the agonist R-PIA modifies the microviscosity of myelin membranes and that the degree of modification depends on the fluidity of the membrane assayed. These results suggest that adenosine receptors may have an important role in the functionality of myelin membranes.

Animals↗
PubMed1991

Two highly effective V1/V2 antagonists of vasopressin containing novel thioacids at position 1.

In an attempt to develop more effective and selective V1/V2 antagonists of arginine vasopressin (AVP), two analogues have been designed and synthesized. In position 1 they contain thioacids that include a heteroatom in the cyclohexane ring. The 4-thio-4-tetrahydrothiopyraneacetic acid modification of position 1 used in one of them had advantages over the 1-mercaptocyclohexaneacetic acid substituted compound used as reference. The new compound was weaker at lower doses, but elicited a greater response at higher doses, whereas the reference compound reached its plateau earlier. Although the 4-thio-4-tetrahydropyraneacetic acid substitution used in the second compound resulted in a less potent analogue on a weight basis, this substitution also confers enhanced overall efficacy in terms of magnitude of effect.

Animals↗
PubMed1991

Presence of adenosine deaminase on the surface of mononuclear blood cells: immunochemical localization using light and electron microscopy.

Adenosine deaminase, which is essential for lymphoid differentiation and function, has previously been considered to be a cytosolic enzyme. In this report we demonstrate that it can be found associated with the plasma membrane of lymphocytes. By means of immunological techniques using both light and electron microscopy, adenosine deaminase was localized on the external side of the plasma membrane of normal lymphocytes and monocytes. Since the enzyme expression differed depending on the type of cell examined, new hypotheses about the mechanisms involving purine metabolism in immune dysfunctions or immunodeficiency syndromes may be considered.

Adenosine Deaminase↗
PubMed1991

Effects of chronic administration of a vasopressin antagonist with combined antivasopressor and antiantidiuretic activities in rats with left ventricular dysfunction.

The present experiments were designed to study the long-term aquaretic effect of [d(CH2)5-D-Tyr(Et)VAVP], an antagonist to arginine vasopressin (AVP) with combined vascular (V1) and renal (V2) receptor inhibiting properties, in rats with left ventricular dysfunction resulting from myocardial infarction (MI). The continuous intravenous infusion of the AVP antagonist (36 micrograms/12 microliters/day) via osmotic minipumps over 11 days resulted in an increase in urine volume and a decrease in urinary osmolality by approximately 10-fold on the first day, but in subsequent days this response decreased in both the post-MI (n = 7) and normal (n = 6) rats. Nevertheless, the daily urine volume remained significantly higher and the urinary osmolality lower in the post-MI rats than in the normal ones throughout the study (p less than 0.05). In two other groups of post-MI (n = 5) and normal (n = 6) rats, intermittent intraperitoneal injections of the AVP antagonist (100 micrograms/kg) every third day resulted in a profound diuresis that was reproducible by each injection and was again significantly greater in the post-MI rats than in the normal rats (p less than 0.05). The cumulative urinary output over the first 10-day period of each treatment was greater with intermittent injections than with continuous infusion in both the post-MI and normal rats, but the difference was significant only in the post-MI rats (398.82 +/- 12.87 ml vs 309.07 +/- 32.44 ml, intermittent vs continuous, respectively, p less than 0.05), even though the cumulative dose of AVP antagonist given intermittently was only about one third of that given continuously.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

[Obstruction of double-J catheter. Obstruction of urinary drainage in the renal unit with double-J catheter. Two different concepts].

We report on three patients with a functioning solitary kidney that required placement of a double-J catheter. All three patients presented with obstruction of urinary drainage within three weeks. In one patient clots were observed inside the catheter. The catheters of the other two patients, however, showed no signs of obstruction. Two patients presented symptoms and signs of reduced volume of diuresis and the other a deteriorated general condition. In patients with a normally functioning contralateral renal unit, deterioration of renal function of the unit with an indwelling double-J catheter may probably go undetected. A compromised urinary drainage of the renal unit with an indwelling double-J catheter is not necessarily associated with obstruction of the catheter lumen. Urinary drainage around an obstructed double-J catheter is not sufficient in all cases.

Adult↗
PubMed1990

Preparative purification of adenosine deaminase from human erythrocytes by affinity chromatography.

The purification of adenosine deaminase from human erythrocytes is reported. By means of classical procedures and by using affinity chromatography as the last step, the enzyme is purified 760,000-fold with a yield of 32%. The affinity resin is composed of purine riboside (nebularine) linked to Sepharose CL6B. Since the compound has no leaving group at the C-6 position the affinity gel is stable and the chromatography can be repeated several times (up to fifteen times in eight months). Purine riboside was chosen because its potency as a reversible inhibitor of adenosine deaminase is greater than that of inosine (a low-affinity inhibitor), but lower than that of erythro-9-(2-hydroxy-3-nonyl)adenine (a high-affinity inhibitor).

Adenosine Deaminase↗
PubMed1990

Control analysis of systems having two steps catalyzed by the same protein molecule in unbranched chains.

The analysis of the control of a metabolic pathway having an enzyme catalyzing two different reactions (or a protein displaying two different activities) has been performed. For such systems although the summation theorems are valid, the flux and concentration connectivity theorems of the metabolic control analysis are not valid. Another general relationship of control analysis is shown to be more widely obeyed and holds in these systems. An exemplary case, where the enzyme catalyzes two irreversible reactions, demonstrates that the level of one internal intermediate is constant, i.e. it does not depend upon the independent variables of the system.

Catalysis↗
PubMed1990

Further characterization of adenosine transport in renal brush-border membranes.

Adenosine transport has been further characterized in rat renal brush-border membranes (BBM). The uptake shows two components, one sodium-independent and one sodium-dependent. Both components reflect, at least partly, translocation via a carrier mechanism, since the presence of adenosine inside the vesicles stimulates adenosine uptake in the presence as well as in the absence of sodium outside the vesicles. The sodium-dependent component is saturable (Km adenosine = 2.9 microM, Vmax = 142 pmol/min per mg protein) and is abolished at low temperatures. The sodium-independent uptake has apparently two components: one saturable (Km = 4-10 microM, Vmax = 174 pmol/min per mg protein) and one non-saturable (Vmax = 3.4 pmol/min per mg protein, Km greater than 2000 microM). Inosine, guanosine, 2-chloroadenosine and 2'-deoxyadenosine inhibit the sodium-dependent and -independent transport, as shown by trans-stimulation experiments, probably because of translocation via the respective transporter. Uridine and dipyridamole inhibited only the sodium-dependent uptake. Other analogs of adenosine showed no inhibition. The kinetic parameters of the inhibitors of the sodium-dependent component were further investigated. Inosine was the most potent inhibitor with a Ki (1.9 microM) less than the Km of adenosine. This suggests a physiological role for the BBM ecto-adenosine deaminase (enzyme which extracellularly converts adenosine to inosine), balancing the amount of nucleoside taken up as adenosine or inosine by the renal proximal tubule cell.

Adenosine↗
PubMed1990

Hormonally inducible phosphorylation of a nuclear pool of ribosomal protein S6.

Thyrotropin releasing hormone (TRH) and epidermal growth factor induce the rapid phosphorylation of a basic, chromatin-associated protein present in GH4 rat pituitary cells and also found in primary hepatocyte culture. Cell fraction experiments indicate a nucleolar localization for this basic, chromatin-associated protein. The protein has been purified to homogeneity from rat liver and 23 amino acids of its N-terminal sequence determined. There is complete homology between the sequenced portion of the basic, chromatin-associated protein and the N-terminal sequence of rat ribosomal protein S6. In vivo and in vitro phosphorylation, two-dimensional gel analysis and two-dimensional tryptic phosphopeptide mapping support the identity of the basic, chromatin-associated protein and S6. Our experimental data indicate the existence of a nuclear pool of S6 whose phosphorylation is hormone inducible.

Amino Acid Sequence↗
PubMed1990

A quantum chemical study of the enzymatic deamination of benzoadenine derivatives. A theoretical model of the interactions occurring between nucleosides and the active site of adenosine deaminase.

A theoretical study is presented, where, by using both ab initio and semi-empirical methodologies, the properties of benzoadenine derivatives as substrates of adenosine deaminase are discussed. The results suggest that lin-benzoadenine and lin-benzoadenosine can be recognized with an affinity similar to that of adenosine, but only if they are introduced about 0.12 nm deeper inside the active site of the enzyme than the natural substrate adenosine. This fact implies the existence of non-linear hydrogen bonds inside the active site of adenosine deaminase. Ab initio molecular electrostatic potential values suggest that these hydrogen bonds can exist, and have stability similar to that of linear hydrogen bonds. Finally, the great rate of deamination of lin-benzoadenine, comparable with that of adenosine despite the absence of the ribose, is explained in the context of the hypothesis that the protonation at the N1 atom is the rate-determining step of the whole deamination reaction.

Adenosine↗
PubMed1990

Adenosine metabolism in kidney slices under normoxic conditions.

The effect of adenosine in rat kidney under normoxic conditions has been studied. It is demonstrated that adenosine modulates cell nucleotide levels. HPLC analysis of the purine compounds inside the cell indicates that adenosine improves the ATP/ADP ratio, whereas it diminishes the adenine content. This behaviour is not due to mediation by specific receptors, as agonists at P1 purinoceptors did not have any effect. Further evidence using inosine as well as dipyridamole and deoxycoformycin indicates that all effects are dependent on the previous uptake of adenosine. The origin of free adenine in the kidney has been investigated, and it appears to come from the phosphorolysis of 5'-methylthio-adenosine. This report is the first to describe the activity of methylthioadenosine phosphorylase (E.C. 2.4.2.28) in the kidney. It is concluded that 1) extracellular adenosine improves guinea pig renal function by increasing the ATP level and the ATP/ADP ratio; and 2) there exists a functional pathway in the kidney that produces adenine and AMP coming from methionine and ATP. This latter pathway probably produces spermine and spermidine, which are likely to be important for renal function.

Adenine↗