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Biomedical subjects

M Gonzalez

Publications and source records attributed to M Gonzalez.

At least 163 records · Page 9Linked to original sources
PubMed1994

Comparative analysis of the behaviors evoked by bromocriptine and quinpirole (LY 171555) in adult cats.

The aim of this work was to compare the behavioral effects of bromocriptine and quinpirole, two agonists of the D-2 dopaminergic receptor, either injected alone or combined with the D-1 dopaminergic receptor, SKF 38393. In ten adult mongrel cats the following experimental series were carried out: i) a dose-response study with bromocriptine administering 0.5-1.0-4.0 and 8.0 mg/kg s.c.; ii) a behavioral study injecting 4.0 mg/kg of bromocriptine plus 2.0 mg/kg of SKF 38393; iii) the same analysis administering 0.5 mg/kg of LY 171555 plus 1.0 mg/kg of SKF 38393, compared with the same dose of LY 171555 plus 4.0 mg/kg of SKF 38393; iv) an analysis of the behavioral effects of 8.0 mg/kg of bromocriptine compared with 1.0 mg/kg of quinpirole. The main findings were: i) bromocriptine injected, in four different doses evoked decrease in locomotion, and increase in indifference, inappetence, pupillary dilation and limb flicks; ii) the combined administration of 4.0 mg/kg of bromocriptine plus 2.0 mg/kg of SKF 38393 did not elicit behavioral changes different to those produced by bromocriptine alone; iii) quinpirole (1.0 mg/kg) evoked more intense behaviors than bromocriptine (8.0 mg/kg); iv) comparing quinpirole injected alone with the combination of quinpirole plus SKF 38393, this latter treatment produced more intense behaviors than the former. It is concluded: i) SKF 38393 potentiates the behavioral effects produced by quinpirole; this potentiation was not found when bromocriptine was combined with SKF 38393 and ii) the more intense behavioral effect elicited by quinpirole compared with bromocriptine may be explained by the fact that the latter drug is a selective D-2 agonist, whereas the former one is an agonist of the D-2 and the D-3 receptors.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1994

Subcellular partitioning of MRP RNA assessed by ultrastructural and biochemical analysis.

A small RNA encoded within the nucleus is an essential subunit of a RNA processing endonuclease (RNase MRP) hypothesized to generate primers for mitochondrial DNA replication from the heavy strand origin of replication. Controversy has arisen, however, concerning the authenticity of an intramitochondrial pool of MRP RNA, and has called into question the existence of pathways for nucleo-mitochondrial transport of nucleic acids in animal cells. In an effort to resolve this controversy, we combined ultrastructural in situ hybridization and biochemical techniques to assess the subcellular partitioning of MRP RNA. Cryosections of mouse cardiomyocytes were hybridized with biotin-labeled RNA probes complementary to different regions of MRP RNA and varying in length from 115 to 230 nucleotides, followed by immunogold labeling. In addition, we transfected mouse C2C12 myogenic cells with constructs bearing mutated forms of the mouse MRP RNA gene and compared the relative abundance of the resulting transcripts to that of control RNAs within whole cell and mitochondrial fractions. In the former analysis we observed preferential localization of MRP RNA to nucleoli and mitochondria in comparison to the nucleoplasm and cytoplasm. In the latter series of studies we observed that wild-type MRP RNA partitions to the mitochondrial fraction by comparison to other RNA transcripts that are localized to the extramitochondrial cytoplasmic space (28S rRNA) or to the nucleoplasm (U1 snRNA). Deletions within 5' or 3' regions of the MRP RNA gene produced transcripts that remain competent for mitochondrial targeting. In contrast, deletion of the midportion of the coding region (nt 118 to 175) of the MRP RNA gene resulted in transcripts that fail to partition to the mitochondrial fraction. We conclude that an authentic intramitochondrial pool of MRP RNA is present in these actively respiring cells, and that specific structural determinants within the MRP RNA molecule permit it to be partitioned to mitochondria.

Animals↗
PubMed1994

Use of fetal ultrasound to select metabolic therapy for pregnancies complicated by mild gestational diabetes.

OBJECTIVE: To determine whether fetal ultrasound early in the third trimester can identify Latina with mild gestational diabetes mellitus (GDM) whose fetuses are at risk for macrosomia and, if so, whether maternal insulin therapy can reduce that risk. RESEARCH DESIGN AND METHODS: Study subjects included 303 consecutive women with GDM and a fasting serum glucose level < 5.8 mM on diet therapy who had a fetal ultrasound between 29 and 33 weeks gestation. Of the women, 98 (32%) had a fetal AC > or = 75th percentile for gestational age, and 59 women completed a randomized trial of diet therapy (n = 29) or diet plus twice daily insulin (n = 30). Maternal nutrient levels were assessed by meal tolerance testing (MTT) before and during therapy and by capillary glucose monitoring four to seven times a day. Birth weights corrected for gestational age and neonatal glycemia and skin folds were the primary outcome variables compared between treatment groups. RESULTS: Diet and diet-plus-insulin groups were well matched for maternal age, prepregnancy relative weight, weight gain during pregnancy, and glycemia at entry. Insulin therapy reduced maternal capillary (P < 0.005) and MTT (P < 0.001) glucose levels and prevented a diet-associated rise in MTT triglyceride levels (P < 0.002). Gestational age at delivery was similar in insulin- and diet-treated groups (39.6 +/- 0.2 vs. 39.5 +/- 0.2 weeks). Birth weights (3,647 +/- 67 vs. 3,878 +/- 84 g; P < 0.02), the prevalence of large-for-gestational age infants (13 vs. 45%, P < 0.02), and neonatal skin-fold measurements at three sites (P < 0.005) were reduced in the insulin-treated group. Rates of transient neonatal hypoglycemia were low in both treatment groups (14 and 18%, respectively) and did not differ significantly between groups. CONCLUSIONS: Fetal ultrasound early in the third trimester identified women with mild GDM whose infants were at high risk for fetal macrosomia in the absence of standard glycemic criteria for insulin therapy. Insulin treatment reduced the macrosomia, indicating that fetal ultrasound can be used to guide metabolic therapy in pregnancies complicated by mild GDM.

Analysis of Variance↗
PubMed1994

Acute lymphoblastic leukemia (ALL): detection of minimal residual disease (MRD) at flow cytometry.

In the present study the usefulness of a method combining multiple staining direct immunofluorescence technique together with flow cytometry in order to predict relapse in ALL is analyzed in a group of 47 patients (11 T-ALL and 36 B-ALL). Results show that this method can be applied to at least two-thirds of all ALL patients being specially useful for the T-ALL cases (100% vs 56%) as this corresponding to the incidence of "aberrant" phenotypes. The detection of an increase in the percentage of bone marrow cells displaying "aberrant" phenotypes in two consecutive samples from the same patient is of great help on predicting relapse (sensitivity of 92% and specificity of 75%).

Adolescent↗
PubMed1994

Low flow veno-venous ECMO: an experimental study.

Clinical use of extracorporeal membrane oxygenation (ECMO) and carbon dioxide removal (ECCO 2R) have become well established techniques for the treatment of severe respiratory failure; however they require full cardiopulmonary bypass, representing major procedures with high morbidity. We theorized the possibility of an efficient low flow veno-venous extracorporeal membrane gas exchange method. Four mongrel 12 kg dogs were submitted to veno-venous extracorporeal membrane gas exchange via a jugular dialysis catheter using a low flow (10 ml/min) roller pump and a membrane oxygenator for a period of four hours. Respiratory rate was set at 4 breaths/min with a FiO 2 of 21% and ventilatory dead space was increased. Adequate gas exchange was obtained (pO 2139, pCO 224, Sat 99.4%), without major hemodynamic changes or hematuria. Our results demonstrate the feasibility of a low flow, less aggressive system. Further research should be considered.

Animals↗
PubMed1994

Applied Sciences: Absence of CD44-standard in human neuroblastoma correlates with histological dedifferentiation, N-myc amplification and reduced survival probability.

Expression of CD44 was examined by immunohistochemistry in 205 primary neuroblastomas together with histological grading according to the Shimada classification at the time of diagnosis. In addition, Southern blot analysis to determine N-myc gene amplification was carried out in the same tissue. When compared with clinical data such as stage, age and event-free survival probability it was found that CD44 expression characterizes well differentiated tumours and thus correlates with prognosis (event-free survival probability in CD44 positive patients 0.6 (n = 129) vs. 0.0 (n = 21) in CD44 negative patients). In tumours with N-myc = 1, CD44 positivity was found in 91% of patients as compared to 57% of patients with N-myc > 1 in tumours. All tumours of 13 patients with metastatic stage 4s (with good prognosis) showed CD44s expression. Thus, detection of CD44s expression might serve as a prognostic indicator which can be rapidly detected at diagnosis.

Journal Article↗
PubMed1993

Effect of isoproterenol on coronary blood flow and signal transduction responses in thyroxine-treated rabbit hearts.

This study examined the hypothesis that treatment with thyroxine (T4) would alter the coronary blood flow and signal transduction responses of the rabbit heart. T4 was administered for 16 days by subcutaneous time-release pellets (3 mg/kg/day) in 3 kg New Zealand white rabbits. Four groups of anesthetized open-chest rabbits (control, control+isoproterenol (ISO, 0.5 microgram/kg/min for 15 min), T4, and T4 + ISO) were used to determine coronary blood flow (radioactive microspheres), cyclic AMP content (competitive binding), low Km cyclic-AMP-phosphodiesterase activity (cyclic AMP-PDE, conversion of 3H-cyclic AMP to 3H-AMP) and beta-adrenoceptor number and affinity (125I-iodocyano-pindolol). Coronary blood flow was increased from control by ISO from 167 +/- 59 to 354 +/- 157 ml/min/100 g. T4 did not cause cardiac hypertrophy, but increased baseline coronary blood flow to 269 +/- 115 ml/min/100 g. The ISO response was attenuated in terms of blood flow (448 +/- 118) and heart rate with T4. Beta-adrenoceptor numbers increased significantly from 65.7 +/- 9.2 to 81.9 +/- 4.4 fmol/mg protein, while neither soluble (126 +/- 39 vs 119 +/- 15 pmol/mg protein/min) nor particulate cyclic AMP-PDE activity were different between control and T4 animals. Cyclic AMP content was increased from control by both ISO (779 +/- 239 to 1371 +/- 672 pmol/g) and T4 (1143 +/- 244). T4 animals showed a smaller increase in cyclic AMP following ISO (1391 +/- 261). There was not a significant difference between the control and T4 group cyclic AMP level following ISO. Thus, despite increased beta-adrenoceptor numbers, there was a diminished responsiveness of heart rate, coronary blood flow and cyclic AMP levels to isoproterenol in the T4-treated rabbit hearts.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1993

Solution and solid-state circular dichroism analyses of a human salivary proline-rich glycoprotein repeating domain and its subfragments.

Solution- and solid-state c.d. spectra, as well as surface energetics values, were collected for a series of peptides derived from human salivary proline-rich glycoprotein (PRG). The acronyms and sequences for these peptides are as follows: PRG9-2 = NH2-G(1)-P(2)-CONH2, PRG9-3 = NH2-G(1)-P(2)-P(3)-CONH2, PRG9-4 = NH2-G(1)-P(2)-P(3)-P(4)-CONH2, PRG9-5 = NH2-G(1)-P(2)-P(3)-P(4)-H(5)-CONH2, PRG9-6 = NH2-G(1)-P(2)-P(3)-P(4)-H(5)-P(6)-CONH2, PRG9-7 = NH2-G(1)-P(2)-P(3)-P(4)-H(5)-P(6)-G(7)-CONH2, PRG9-8 = NH2-G(1)-P(2)-P(3)-P(4)-H(5)-P(6)-G(7)-K(8)-CONH2, and PRG9-9 = NH2-G(1)-P(2)-P(3)-P(4)-H(5)-P(6)-G(7)-K(8)-P(9)-CONH2. The presence of stable poly-L-proline II-like 'mini' helices in the solution state was found to be dependent on peptide chain length, pH, salt, and organic solvent type. Other conformational features such as kinks and beta-/gamma-turns were also found in the larger peptides. Solid-state peptide conformations were not necessarily related to their solution-state counterparts. Poly-L-proline II-like 'mini' helices, kinks, and beta-/gamma-turns were similarly found in the various substrate-bound PRG9 peptides. Surface energetics parameters suggested specific orientations for PRG9 peptides and their constituent acids and homopolymers.

Circular Dichroism↗
PubMed1993

Effects of SCH 23390 and sulpiride on the behaviors evoked by amphetamine and apomorphine in adult cats.

1. The aim of the present study was to analyze whether the dopaminergic D1 and D2 receptors are involved in the production of the behaviors evoked by parenteral administration of amphetamine and apomorphine in adult cats. 2. Fifteen mongrel cats of both sexes were injected, in separate sessions, with 2.5 mg/kg of amphetamine and 2.0 mg/kg of apomorphine. The D1 receptor blocker, SCH 23390 was administered (0.3 mg/kg i.p.) and after 60 min, amphetamine and apomorphine were again injected on different days. The same procedure was carried on with sulpiride in two doses (20 and 30 mg/kg i.p.). The behaviors induced by the two dopaminergic drugs, before and after the receptor blocker administration were respectively compared. The Wilcoxon signed rank test was employed for statistical analysis. Three independent observers recorded the behaviors. 3. SCH 23390 and sulpiride produced per se hypomotility and sedation, effects that were considered when analysing the results. Some of the behaviors produced by amphetamine (pupillary dilation, head movements) were slightly modified by both receptor blockers. SCH 23390 only modified the licking behavior produced by apomorphine. In contrast, sulpiride blocked almost all the behaviors elicited by apomorphine, especially when the 30 mg/kg dose was administered. It is concluded that the behaviors produced by the 2 mg/kg dose of apomorphine are evoked by its binding to the post-synaptic dopaminergic D2 receptors and blocked by sulpiride.

Amphetamine↗
PubMed1993

Role of ischemia-reperfusion on myocardial cyclic AMP and cyclic AMP phosphodiesterase: effects of amrinone on regional myocardial force and shortening.

This study tested the hypothesis that a reperfused ischemic myocardial region of the dog heart would be unable to increase its function in response to amrinone, a specific cyclic AMP phosphodiesterase (cAMP-PDE) inhibitor, due to loss of cAMP-PDE activity in the region. The global contractility (+dp/dtmax), regional percent shortening (ultrasonic crystals), and developed force (miniature force gauge) were measured on a continuous basis throughout a 6-hour experiment and regional blood flow (radioactive microspheres) in open-chest pentobarbital-anesthetized mongrel dogs. The left anterior descending coronary artery (LAD) was isolated and ligated for 2 hours and allowed to reperfuse for 4 hours. This myocardial region was compared to a nonischemic region supplied by the circumflex artery. At the end of the 4-hour reperfusion period, 9 dogs were treated with amrinone (5 mg/kg) and three dogs were not treated with amrinone. The hearts were rapidly excised and frozen in liquid nitrogen. Cyclic AMP and cAMP-PDE activity was determined in homogenates of myocardial tissue. Blood flow decreased during occlusion in the LAD region and returned toward control with reperfusion. Flow increased nonsignificantly with amrinone. the basal cyclic AMP content of the two regions was not different. The cAMP-PDE activity was reduced 24% in the LAD region compared to the control region. There were no ischemia-induced changes in the enzyme characteristics. These experiments demonstrated increased global function in the ischemic reperfused myocardium after amrinone was administered (dP/dtmax: 2092 +/- 538 to 3277 +/- 688 mmHg/sec).(ABSTRACT TRUNCATED AT 250 WORDS)

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1993

Phenofibrate-induced lichenoid photodermatitis.

Phenofibrate is an hypolipemiant drug derived from fibric acid. Cutaneous side effects such as pruritus, rash, urticarial lesions and some rare cases of photosensitivity have been described (1-3). The reported photosensitivity cases are clinically described as eczematous (1-3); some have been reproduced by photopatch-testing (2, 3). We studied a patient with a clinical and histopathological lichenoid eruption over light-exposed areas clearly related to phenofibrate therapy for an essential hypercholesterolemia.

Dermatitis, Photoallergic↗
PubMed1993

Neoadjuvant and salvage chemotherapy with cisplatin (CDDP) and 5-fluorouracil (5-FU) in cervical carcinoma.

A regime of cis-platin (CDDP) (80 mg/m2) and 5-fluorouracil (5-FU) (1000 mg/m2/day, day 1 to 5) repeated after 21 days, was prospectively analyzed in 12 advanced epidermoid cervical cancers as first treatment, prior to radiotherapy (neoadjuvant chemotherapy), and in 30 cases of progressive, recurrent or metastatic disease after radiotherapy (salvage chemotherapy), in order to evaluate efficacy and toxicity. Among the 10 evaluable neoadjuvant cases we observed 2 complete, 7 partial responders and 1 stabilized. They all achieved a complete response after radiotherapy and 6 remain alive after 18 to 72 months. None of the salvaged patients achieved a complete response and only 26.9% responded partially. Only one case, though fatal, of myelodepression was found in the neoadjuvant group. Conversely, 70% of salvages showed some grade of myelodepression, being severe or extremely severe in 23.3%, with another case of death. Neoadjuvant chemotherapy with CDDP and 5-FU seems promising in advanced cervical carcinoma and is acceptably well tolerated. In contrast, salvage therapy with the same regime yields worse results and is much more toxic.

Adult↗
PubMed1992

Effects of Na+ transport inhibitors on guinea-pig tracheal responses to spasmogens.

The effects of ouabain, amiloride, K(+)-free solution and low Na+ (25 mM) solution on the responses to CaCl2 (in Ca(2+)-free, K(+)-depolarizing solution), KCl, acetylcholine, histamine and 5-hydroxytryptamine were studied in guinea-pig isolated trachea. Ouabain (10 microM) did not alter the contractile responses to CaCl2, KCl and acetylcholine but depressed those to histamine and 5-hydroxytryptamine produced in normal Ca2+ (2.5 mM) and Ca(2+)-free (EGTA 0.1 mM) media. Amiloride (0.1 mM), K(+)-free solution, and low Na+ solution depressed responses to acetylcholine, histamine and 5-hydroxytryptamine produced in normal Ca2+ and Ca(2+)-free media. Ouabain and amiloride had no effect on responses of skinned strips to Ca2+. The mechanism of the inhibitory effects of these interventions is uncertain but the findings suggest that the availability of Na+ influences the airway smooth muscle responses to spasmogens.

Acetylcholine↗