Search PubMed⌕ Search

Biomedical subjects

R Alvarez

Publications and source records attributed to R Alvarez.

At least 199 records · Page 11Linked to original sources
PubMed1990

Stimulation of renal and hepatic c-myc and c-Ha-ras expression by unilateral nephrectomy.

Unilateral nephrectomy induces compensatory hypertrophy of the contralateral kidney in rats, resulting in a 25% weight increase in 14 days. We have demonstrated that expression of the c-myc and c-Ha-ras protooncogenes is increased more than ten-fold in the contralateral kidney within 4 to 8 hr following unilateral nephrectomy in rats. The increased expression of these genes is analogous to the increased expression of c-myc and c-Ha-ras that occurs early in liver regeneration, preceding the first increase in DNA synthesis by at least 20 hr. In order to define the tissue specificity of the signals for compensatory renal hypertrophy, we also determined the early protooncogene response and the proliferative response in the liver of rats following unilateral nephrectomy. The expression of c-myc and c-Ha-ras was also increased (five- to ten-fold) in the livers of these animals. DNA synthesis was stimulated in the contralateral kidney at 26-30 hr following nephrectomy as measured by 3H thymidine incorporation, indicating a hyperplastic response to unilateral nephrectomy. However, there was no increase in DNA synthesis in the liver despite the dramatic increase in c-myc and c-Ha-ras expression. Our data suggest that the early increase in protooncogene expression in response to unilateral nephrectomy is stimulated by circulating signals that are not tissue-specific. Increased protooncogene expression in both kidney and liver following unilateral nephrectomy is an early response to the regenerative stimulus, but later signals must provide the tissue specificity necessary for regeneration and cellular proliferation.

Animals↗
PubMed1989

[Meningoencephalomyelitis caused by Borrelia burgdorferi: a case without epidemiologic history or chronic migratory erythema].

A patient is reported with meningoencephalomyelitis with polyradiculitis caused by Borrelia burgdorferi infection. Neurological features developed without previously known tick bite nor the characteristic skin lesion, chronic migratory erythema (CME). The vector of the disease (the tick Ixodes ricinus) exists in Spain, but only one case of meningopolyradiculitis with CME has been reported in Asturias. Our case stresses that B. burgdorferi infection should be suspected in cases of meningoencephalomyelitis or meningopolyradiculitis even without previous skin or joint lesion.

Adult↗
PubMed1989

Relationship between Indole-3-Acetic Acid Levels in Apple (Malus pumila Mill) Rootstocks Cultured in Vitro and Adventitious Root Formation in the Presence of Indole-3-Butyric Acid.

In vitro rooting response and indole-3-acetic acid (IAA) levels were examined in two genetically related dwarfing apple (Malus pumila Mill) rootstocks. M.26 and M.9 were cultured in vitro using Linsmaier-Skoog medium supplemented with benzyladenine (BA), indole-3-butyric acid (IBA), and 1,3,5-trihydroxybenzoic acid (PG). Rooting response was tested in Lepoivre medium supplemented with IBA and PG. IBA concentrations of 12.0 and 4.0 micromolar induced the maximum rooting percentages for M.9 and M.26, respectively. At these concentrations rooting response was 100% for M.26 and 80% for M.9. Free and conjugated IAA levels were determined in M.26 and M.9 shoots prior to root inducing treatment by high performance liquid chromatography with fluorescence detection and validated by gas chromatography-mass spectrometry using (13)[C(6)]IAA as internal standard. Basal sections of M.26 shoots contained 2.8 times more free IAA than similar tissue in M.9 (477.1 +/- 6.5 versus 166.6 +/- 6.7 nanograms per gram fresh weight), while free IAA levels in apical sections of M.26 and M.9 shoots were comparable (298.0 +/- 4.4 versus 263.7 +/- 9.3 nanograms per gram fresh weight). Conjugated IAA levels were significantly higher in M.9 than in M.26 indicating that a greater proportion of total IAA was present as a conjugate in M.9. These data suggest that differences between M.26 and M.9 rooting responses may be related to differences in free IAA levels in the shoot base.

Journal Article↗
PubMed1989

Development of the child's arch.

The purposes of the project were to monitor the development of the lower extremities and the longitudinal arch of the foot and to determine whether or not arch support footwear (three types) affected development of a neutral arch in toddlers 11 to 14 months of age until age 5 years. A total of 125 beginner walkers were recruited through the pediatrics department during a period of 1 1/2 years and divided by lot into four different footwear groups (one nonarch supportive). The group was studied for 4 years by physical examinations, x-ray films, and pedotopography (a Moire fringe technique of photography). At initial examination all of the apparently normal toddlers had pes planus by all clinical, roentgenographic, and photographic measurements. There were no cavus feet at that time or at 5 years of age. Arches developed regardless of the footwear worn but development was faster during the first 2 years (until age 3 years) with arch support footwear. The rapidity of arch development until 5 years of age continued in those children who wore longitudinal arch cookies. Ossification of the sustentaculum tali begins at approximately 5 years of age but is not complete for at least another 1 to 2 years. Hyperpronation was present in 77.9% and genu valgum in 92.3% of the 5-year-old children. These conditions are apparently the norm at this age in both boys and girls.

Child, Preschool↗
PubMed1989

Biologicals production by recombinant DNA technology in Cuba.

During 1981 we started an intensive programme for the development of biotechnology in Cuba. The first project was related to the production of leucocyte interferon and the cloning an expression of these genes in prokaryotic and yeast cells. These products are currently obtained in large amounts and their physical and chemical characterization are presented. The use of mammalian cells in culture for the production of recombinant proteins has also been carried out. The results obtained with the expression and amplification of the hepatitis B surface antigen (HBsAg) in CHO cells are discussed and compared with that obtained in yeast. The construction of a recombinant vaccinia virus carrying the HBsAg was also achieved. The specific transcripts were characterized and the Ab levels tested in animals. The results presented here indicate that the host system is a very important aspect to be taken into consideration and in some cases mammalian cells appear to be the best choice.

Animals↗
PubMed1989

Stimulation of protooncogene expression by partial hepatectomy is not tissue-specific.

We have characterized the early protooncogene response and the later cell proliferative response in the kidneys and livers of normal rats cross-circulated with partially hepatectomized animals. Increase c-myc and C-Ha-ras expression was observed in the kidneys of totally hepatectomized rats, as well as those of their cross-circulated partners. This indicates that the initial response to hepatectomy is not organ-specific, although the later DNA synthetic response of the kidney is only approximately one-tenth that of regenerating liver. Expression of c-myc and c-Ha-ras is dramatically increased in the livers of both hepatectomized and nonhepatectomized, parabiotic (cross-circulated) rats within 1 hr of partial hepatectomy, confirming the presence of a circulating factor which stimulates protooncogene expression early in regeneration. DNA synthesis was also stimulated in the livers of the cross-circulated animals between 20 and 26 hr following hepatectomy, but only to a level one-eighth that of the livers of hepatectomized animals. Normal rats cross-circulated with totally hepatectomized animals also demonstrated an early increase in hepatic c-myc and c-Ha-ras expression, indicating that regeneration must be stimulated by an extrahepatic signal. Our data suggest that the early increase in protooncogene expression is a non-organ-specific response to partial hepatectomy which does not insure subsequent cellular proliferation. The organ specificity of liver regeneration must involve an event separate from the early stimulation of protooncogene expression.

Animals↗
PubMed1988

Inhibitors of cyclic AMP phosphodiesterase. 3. Synthesis and biological evaluation of pyrido and imidazolyl analogues of 1,2,3,5-tetrahydro-2-oxoimidazo[2,1-b]quinazoline.

Hybridization of structural elements of 1,2,3,5-tetrahydro-2-oxoimidazo[2,1-b]quinazoline ring system common to the cyclic AMP (cAMP) phosphodiesterase (PDE) inhibitors lixazinone (RS-82856, 1) and anagrelide (3) with complementary features of other PDE inhibitor cardiotonic agents prompted the design and synthesis of the title compounds 7a-d, 11, 12, and 13a,b. The necessary features of these compounds were determined within the framework of the proposed active-site models for the high affinity form of cAMP PDE inhibited by cGMP (type IV). Evaluation of these targets, both in vitro as inhibitors of platelet or cardiac type IV PDE or in vivo as inotropic agents in the pentobarbital-anesthetized dog model of congestive heart failure, showed that these structure possessed negligibly enhanced activities over the parent heterocyclic system, and remained significantly inferior to 1 in all respects. This difference is ascribed to the absence of the N-cyclohexyl-N-methylbutyramidyl-4-oxy side chain of 1. The proposal that the acidic lactam-type functionality, common to the type IV PDE inhibitor inotropic agents such as 4-6 and 8-10, mimics the polarizable cyclic phosphate moiety of cAMP suggested that the side chain of 1 may function as an effective surrogate for selected characteristics of the adenine portion of cAMP. However, the results of this study show that incorporation of adenine-like hydrogen-bonding functionalities common to other type IV PDE inhibitors into the 1,2,3,5-tetrahydro-2-oxoimidazo[2,1-b]quinazoline system did not enhance activity to the levels observed for 1 and analogues. These observations, coupled with the kinetic pattern of inhibition of type IV PDE observed for 1 and analogues, suggest that access to a secondary, lipophilic-tolerant binding site, possibly coincident with the adenine binding domain, and adjacent to the catalytic ribose-phosphate binding site of platelet and cardiac type IV PDE, is responsible for the increased potency of these compounds.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1988

Inhibitors of cyclic AMP phosphodiesterase. 4. Synthesis and evaluation of potential prodrugs of lixazinone (N-cyclohexyl-N-methyl-4-[(1,2,3,5-tetrahydro-2- oxoimidazo[2,1-b]quinazolin-7-yl)-oxy]butyramide, RS-82856).

The cyclic AMP phosphodiesterase (cAMP PDE) inhibitor and cardiotonic agent lixazinone (N-cyclohexyl-N-methyl-4-[(1,2,3,5-tetrahydro-2- oxoimidazo[2,1-b]quinazolin-7-yl)oxy]butyramide, RS-82856, 1) and its acid and base addition salts were found to be insufficiently soluble in formulations suitable for intravenous administration. These results prompted an investigation into potential prodrugs with enhanced aqueous solubility designed to deliver 1 by three distinct mechanisms: (1) decarboxylation of alpha-carboxamides; (2) hydrolytic loss of a solubilizing N-1-(acyloxy)methyl or (N,N-dialkylamino)methyl moiety; or (3) intramolecular closure of a guanidino ester or amide. The target compounds were evaluated as delivery systems for 1 by three criteria: (1) chemical conversion rate to 1 under physiological conditions; (2) inhibition of type IV cAMP PDE at a fixed time point; and (3) in vivo inotropic activity in anesthetized dogs by both intravenous and oral administration. Release of 1 from 4a (series 1) was found to be too slow to be of value as a prodrug of 1, since decarboxylation could be induced only by strong acid, conditions under which hydrolytic ring opening was found to severely compete. Conversely, 1 was released too readily on exposure of (N,N-dialkylamino)methyl derivatives such as 8d (series 2) to physiological conditions, although no large increase in aqueous solubility was realized. Finally, both the physicochemical and in vitro studies indicated that ring closure of the guanidinium esters and amides 17a-k (series 3) to 1 was quantitative and pH- and time-dependent, suggesting the possibility of delivery of the open, water-soluble prodrug form, followed by closure to 1 in plasma. Detailed examination of these agents in vivo, however, demonstrated that only those compounds that rapidly cyclized to 1, as measured by plasma levels of 1, exhibited inotropic activity, indicating that the open prodrug form was not efficiently absorbed upon oral administration.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1988

Induction of bilirubin-eliminating processes by methylphenobarbital in mature newborn babies.

In order to find a drug for the prevention of metabolic hyperbilirubinemia of the newborn, which has less sedative effects than phenobarbital (PB) the effect of methylphenobarbital (MPB) on the plasma bilirubin concentration of newborns was studied in a double blind trial. MPB (3 x 10 mg/kg on the first day) reduced the plasma bilirubin level in mature newborns on day four by 33% in comparison to those on placebo. The results justify further investigations in premature babies, who frequently suffer from disturbances which may facilitate the development of bilirubin encephalopathy.

Bilirubin↗
PubMed1988

Impaired production and lack of secretion of interleukin 1 by human breast milk macrophages.

Interleukin 1 (IL-1) production by human breast milk macrophages (HMMø) in response to bacterial lipopolysaccharides (LPS) was investigated in 49 healthy mothers and compared with that of blood monocytes (HMo). IL-1 activity in 24 h HMMø culture supernatants was in most cases below the assay detection limits and much smaller than that of stimulated HMo (72 +/- 17 u/ml). Intracellular IL-1 activity in response to LPS in HMMø raised from less than 2 +/- 1 u/ml to 19 +/- 12 u/ml and was similar to that found in stimulated HMo (16 +/- 4 u/ml). Neither the low IL-1 production by HMMø nor its release into supernatants could be increased by stimulating with higher LPS concentrations (40-400 micrograms/ml) or when longer culture times were assayed (24-72 h). Inhibiting the production of prostaglandins by adding indomethacin to HMMø cultures, caused no effect either on IL-1 production or on its secretion to supernatants. The presence of inhibitors for the IL-1 thymocyte proliferative assay, in supernatants from HMMø, was excluded by mixing experiments with a known amount of IL-1. Thus, we conclude that HMMø produce four or five times less IL-1 than HMo in response to LPS stimulus. Furthermore, HMMø are completely unable to release the IL-1 produced.

Adolescent↗
PubMed1988

Dimensional changes of the feet in pregnancy.

Serial measurements of the volume, length, and width of the feet of seventeen pregnant women were made at, or close to, the thirteenth and thirty-fifth weeks of pregnancy and eight weeks postpartum. The same measurements were made twice on a control group of sixteen nulliparous women at intervals that ranged from sixteen to twenty weeks. There was no change in the length or width of the feet in either group. The mean volume of the feet increased 57.2 milliliters between early and late pregnancy (p less than 0.001) and decreased by only 8.42 milliliters between late pregnancy and eight weeks postpartum. These changes were attributed to retention of fluid or to an increase in soft tissue and not to stretching or relaxation of the ligaments.

Adult↗
PubMed1987

IgM response and resistance to ascites tumor growth.

Antibody response and protection against Ehrlich ascites tumor (EAT) was studied in eight EAT-immunized strains of mice (AL/N, BALB/C, C57BL/6J, F1 (C57BL/6 x BALB/C), C57BL/10J, B10.BR, CBA/Ca, SW). The results showed a close association between IgM response and resistance to subsequent tumor challenge. Thus, protection was only achieved in those animals giving a measurable IgM response against EAT cell surface antigens, i.e., all inbred strains of mice tested, except CBA/Ca, and some outbred SW mice. The lack of IgM response to these antigens in CBA/Ca was not linked to the strain H-2 haplotype. Resistance could be passively transferred to nonimmunized mice by means of serum, or purified IgM, from protected immune animals. Moreover, complement depletion by cobra venom factor treatment did not modify the protection afforded to those mice. IgM reactivity to EAT cells was completely abolished by previous cell trypsinization. Trypsin removed but did not destroy the antigen(s) recognized by the IgM, since all its activity could be absorbed with the supernatant of the EAT cell trypsinization. Absorption assays with this supernatant treated with different agents, showed that lipids, simple peptides and nucleic acids were not important components of the antigenic determinants. On the contrary, its susceptibility to beta-galactosidase and particularly to a mild periodate oxidation, suggested that determinants recognized by the IgM against the EAT cell surface are carbohydrate in nature.

Animals↗
PubMed1987

Inhibitors of cyclic AMP phosphodiesterase. 1. Analogues of cilostamide and anagrelide.

Evaluation of a series of lactam heterocyclic analogues of cilostamide (2) as inhibitors of cyclic AMP phosphodiesterase derived from both human platelets and rat heart in comparison with their corresponding methoxy-substituted heterocycles has revealed that the N-cyclohexyl-N-methyl-4-oxybutyramide side chain of 2 is an important lipophilic and/or steric pharmacophore. Attachment of this side chain to the parent heterocycle of the potent cyclic AMP phosphodiesterase inhibitor anagrelide (3) afforded the hybrid structure RS-82856 (1), shown to be more potent than either of its progenitors as an inhibitor of cyclic AMP phosphodiesterase or of ADP-induced platelet aggregation. The available in vitro data suggest that 1 possesses potentially useful antithrombotic and cardiotonic properties.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1987

Inhibitors of cyclic AMP phosphodiesterase. 2. Structural variations of N-cyclohexyl-N-methyl-4-[(1,2,3,5-tetrahydro- 2-oxoimidazo[2,1-b]quinazolin-7-yl)-oxy]butyramide (RS-82856).

A series of analogues of the cyclic AMP phosphodiesterase (PDE) inhibitor N-cyclohexyl-N-methyl-4-[(1,2,3,5-tetrahydro- 2-oxoimidazo[2,1-b]quinazolin-7-yl)oxy]butyramide (RS-82856, 1) was prepared by systematic variation of the side-chain substituent, length, position, connecting atom, and the parent heterocycle itself. The compounds were evaluated as inhibitors of cyclic AMP phosphodiesterase from both human platelets and rat or dog heart tissue and as inhibitors of ADP-induced platelet aggregation. Structure-activity correlations for the analogue series revealed significant limitations on the steric bulk of substituents on the 1,2,3,5-tetrahydroimidazo[2,1-b]quinazolin-2-one heterocycle and the position and length of the side chain. As inhibitors of cyclic AMP phosphodiesterase (PDE), potency steadily increased with increasingly lipophilic side chains. In platelet aggregation inhibition studies, however, a maximum in activity was reached with 1, while more lipophilic compounds were significantly less active. Major changes in the heterocycle itself, represented by isomeric and other carbonyl variations, also decreased activity. The molecular features defined by this series of analogues of 1 correlate to a high degree with current understanding of the chemical and topographical requirements of the active site of the FIII (type IV) form of cyclic AMP PDE. Selective inhibition of this enzyme has been proposed as the principal component of the positive inotropic action of a number of cardiotonic agents.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1987

Slimming treatment efficiency and changes in serum lipids and lipoproteins in obese adolescents.

The efficiency of a slimming treatment, which is the quantity of lean body mass (LBM) lost for each kilogram of body fat reduced, measured by Efficiency Index (EI), was investigated in nineteen obese male adolescents aged 10-14 years who lost weight during four weeks of a treatment combining hypoenergetic diet (0.18 MJ/kg of expected body weight for stature), physical exercise and psychological support. Anthropometric assessment of adiposity including body composition using Parízková and Roth's regression equations was made before onset of treatment and after 7, 14 and 28 days. Simultaneously, blood samples were drawn for serum lipids and lipoproteins. A total of seventy six observations and assessments of treatment efficiency and changes of lipid profile between every two observations were carried out. Significant correlations were found between EI values and changes in Total Cholesterol and Total Cholesterol/HDL Cholesterol ratio at the three evaluations carried out. Though HDL-Cholesterol level increase was not significant, its variations were strongly correlated with EI during the first and second assessments. Differences found in the magnitude of increase in nonesterified fatty acids (delta NEFA), suggest that lipolytic mechanisms were not uniformly impaired. Treatment efficiency and delta NEFA were lower in subjects with lesser adiposity related to muscle mass at the middle third of the upper arm (measured through Energy/Protein Index). Triglycerides and LDL + VLDL Cholesterol levels showed little variations. The achievement of a high treatment efficiency is not only necessary for preserving growth, but also for the significant decrease which occurs in some lipid fractions when EI is below 0.5.

Adolescent↗
PubMed1987

Diagnostic peritoneal lavage in the management of blunt abdominal trauma: a reassessment.

In order to reassess the value of diagnostic peritoneal lavage (DPL) in patients with blunt abdominal trauma, we conducted a prospective study over a 15-month period involving 138 patients. There were 29 (28.3%) patients with positive DPL and 103 (71.7%) with negative DPL in this series. Of the 29 patients with positive DPL, 28 (96.5%) were found to have significant intra-abdominal injuries; 27 by exploratory laparotomy and in one case at autopsy. One patient with a grossly positive DPL had a negative exploratory laparotomy (3.4% false positive rate). All 109 patients with negative DPL were admitted. In only one case a significant intra-abdominal injury was demonstrated (0.9% false negative rate). The overall mortality in this series was 11.6% and there were no complications related to the DPL. Our results suggest that DPL is indeed an accurate indicator of significant intra-abdominal injuries in patients with blunt abdominal trauma.

Abdominal Injuries↗