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Biomedical subjects

E Rodriguez

Publications and source records attributed to E Rodriguez.

At least 127 records · Page 7Linked to original sources

Recent studies on the zoopharmacognosy, pharmacology and neurotoxicology of sesquiterpene lactones.

Aspects of recent research on the biological activities of sesquiterpene lactones (SQLs) are presented. Several SQLs have been identified as important constituents of plants consumed by animals for presumed medicinal value and is a focus of research in zoopharmacognosy. Recent in vivo antitumor studies with parthenin and eupatoriopicrin are discussed as well as the reports of the antiulcer activity of dehydroleucodin. Helenalin has recently been reported to have cardiotonic activity. Research on the neurotoxicity of repin, a compound reported to cause a Parkinson's-like disease in horses, is also highlighted.

Animals↗

An expert system based preventive medicine examination adviser.

Periodic preventive medicine examinations generally rely on a standardized approach. In addition, they are often performed by physicians with only limited training in preventive medicine. Evaluation of a corporate-based program led to the prototype development of an artificial intelligence (AI)-based expert system to collect information from employees and make very specific recommendations for primary practitioners. Unique features include the customizing of questions for each subject and the selection of information to be acquired, both based on answers to previous questions. Recommendations are highly person specific and fall into four categories: laboratory testing, primary physician testing, counseling, and referral. The AI approach allows for easy updating of recommendations in order to meet changes in local preventive resources and national recommendations.

Artificial Intelligence↗

Relationship between cGMP and myocardial O2 consumption is altered in T4-induced cardiac hypertrophy.

We tested the hypothesis that increases in guanosine 3',5'-cyclic monophosphate (cGMP) would reduce myocardial O2 consumption and that thyroxine (T4)-induced (0.5 mg/kg for 16 days) cardiac hypertrophy would change this relationship. Anesthetized open-chest New Zealand White rabbits were divided into four groups: control vehicle (CV, n = 7), control nitroprusside (CN, n = 6), T4 vehicle (T4V, n = 8), and T4 nitroprusside (T4N, n = 8). Vehicle or sodium nitroprusside (10(-4) M) was topically applied to the left ventricular subepicardium for 15 min. Coronary blood flow (radioactive microspheres) and O2 extraction (microspectrophotometry) were used to determine O2 consumption. Guanylate cyclase activity and cGMP were determined by radioimmunoassay. T4 increased the heart weight-to-body weight ratio from 2.7 +/- 0.1 to 3.4 +/- 0.2. Topical application of nitroprusside had no significant hemodynamic effects. Nitroprusside significantly increased myocardial cGMP in control hearts (CV = 4.1 +/- 0.3 to CN = 12.4 +/- 5.0 pmol/g) and T4 hearts (T4V = 3.9 +/- 0.3 to T4N = 5.2 +/- 0.4). The increase in the level of myocardial cGMP was significantly greater in CN (+202%) than in T4N (+33%). There were no significant differences in basal or total guanylate cyclase activity between control and T4 rabbits. Myocardial O2 consumption significantly declined in both groups during nitroprusside (10.8 +/- 1.4 for CV to 7.3 +/- 1.0 for CN (-32%) and 13.6 +/- 1.2 for T4V to 9.9 +/- 1.4 ml O2.min-1.100 g-1 for T4N (-27%).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Molecular and cytogenetic studies in the diagnosis of patients with poorly differentiated carcinomas of unknown primary site.

PURPOSE: A minority of patients with poorly differentiated carcinoma achieve a complete response to cisplatin therapy. Recently, specific chromosomal abnormalities have been described for several solid tumor malignancies. Molecular and cytogenetic techniques were used to study tumors of patients with midline carcinoma of unknown primary site. MATERIALS AND METHODS: Forty patients with poorly differentiated carcinoma of unknown primary site had fresh tumor samples studied by cytogenetic analysis, Southern blot analysis for 12p copy number, and fluorescence in situ hybridization (FISH) for the identification of i(12p) and chromosome 12 aneuploidy. The response to cisplatin therapy was correlated to the diagnosis provided by the genetic studies. RESULTS: In 17 (42%) patients, a diagnosis was suggested by the genetic studies. This included a germ cell tumor in 12 (30%) patients by the finding of i(12p), increased 12p copy number, or a deletion of the long arm of chromosome 12. In five patients, a specific diagnosis other than germ cell tumor was suggested by tumor karyotype. These were neuroepithelioma, lymphoma, desmoplastic small-cell tumor, melanoma, and clear-cell sarcoma. The 75% response proportion to cisplatin therapy in patients with tumors showing chromosome structural abnormalities of germ cell tumor was greater than the 18% response proportion in patients for whom no diagnosis was provided (P = .002). CONCLUSION: Molecular and cytogenetic studies are useful in establishing specific diagnoses in patients with poorly differentiated carcinomas of unknown primary site. This group of tumors is heterogeneous and is composed of germ cell tumors, melanoma, lymphoma, neuroepithelioma, and desmoplastic small-round-cell tumor in addition to some that are not yet classifiable. Response to cisplatin therapy correlates with the finding of i(12p) in tumor by either molecular or cytogenetic studies.

Adenocarcinoma↗

The anatomical substrates for language and hemispheric specialization.

Three main lines of investigation are discussed in this paper: (1) the comparison between the anatomical arrangement of the language areas and the large-scale neurocognitive cortical networks partly involved in active or working memory; (2) the relations between hemispheric specialization and the development of interhemispheric communication; and (3) the analysis of individual differences in brain organization for language. The hypothesis and evidence presented stem from work being performed in our laboratories.

Cerebral Cortex↗

Loss of heterozygosity and decreased expression of NME genes correlate with teratomatous differentiation in human male germ cell tumors.

Embryonal carcinoma in the human male is a pluripotential germ cell tumor (GCT), which is suggested to further differentiate to teratoma which displays somatic differentiation representing all three germinal layers. In a panel of 37 GCTs we determined frequency of loss of heterozygosity (LOH) and the level of expression of nucleoside diphosphate kinase (NDPK) genes NME 1 and NME 2. The frequency of LOH in teratomas (86%) was found to be highly significant (P < 0.01) compared to embryonal carcinomas (17%). We also found that the NME encoded proteins are expressed at a 4-5 fold lower level in teratomas compared to embryonal carcinomas. These findings lead us to hypothesize that a critical level of NDPK may be necessary for suppression of aberrant somatic differentiation.

Gene Expression↗

Genetic changes in epithelial solid neoplasia.

Although chromosomal analysis of solid epithelial neoplasms has lagged behind that of hematopoietic, mesenchymal, and germ cell tumors, gradual accumulation of data over the past 5 years enables development of a general view. Thus, these tumors appear to be characterized by a set of nonrandom deletions the incidence of which varies in tumors of different histological types. Most tumors were studied at advanced stages; therefore, essentially no data are available on the cytogenetic characteristics of the earliest stages of tumorigenesis. In contrast to the status of cytogenetic data, a large body of information on deletions at the molecular level assayed by the loss of heterozygosity analysis has accumulated over the same period. These data have been less complete than the cytogenetic data, although in cases such as colorectal carcinoma, genetic changes from the earliest to the most advanced stages have been studied in detail providing a genetic view of progression. Equally important is the fact that deletion mapping studies by the loss of heterozygosity assay directly lead to isolation of a number of tumor suppressor genes. A comparison of the pattern of deletions identified by chromosomal and loss of heterozygosity analysis revealed, as expected, a concordance. Comparison of the patterns of chromosomal (and the underlying molecular) changes in tumors between major embryological cell types demonstrates fundamental differences in genetic mechanisms which lead to tumorigenesis.

Chromosome Aberrations↗

Origin of adult male mediastinal germ-cell tumours.

The origin of primary extragonadal germ-cell tumours, especially mediastinal and pineal germ-cell tumours in adult males remains uncertain, although the predominant view is that they originate in misplaced primordial germ cells retained in extra-gonadal sites, in contrast to gonadal germ-cell tumours which are considered to arise in premeiotic spermatocytes. We hypothesised that if mediastinal germ-cell tumours and gonadal germ-cell tumours were derived from precursor cells in different developmental states and in different cellular environments, non-random genetic changes in the two groups would be significantly different. To test this hypothesis, we compared non-random chromosomal abnormalities in mediastinal germ-cell tumours with those in gonadal germ-cell tumours. Our results show that although the two groups differed in the composition of histological subsets, their non-random chromosomal changes were essentially the same. These data suggest gonadal origin of all germ-cell tumours with occasional migration of precursors early in development to extragonadal sites to become established as primary extragonadal germ-cell tumours. Based on a review of cytogenetic data on carcinoma in situ, primary mediastinal and gonadal germ-cell tumours, embryonal migration of primordial germ-cells, and meiotic behaviour of spermatocytes, a model of origin of all germ-cell tumours in males is suggested.

Adult↗

Clinical relevance of the i(12p) marker chromosome in germ cell tumors.

BACKGROUND: Germ cell tumors in men are curable at all stages and are among the most sensitive of all cancers to chemotherapy. An isochromosome of the short arm of chromosome 12, i(12p), has been reported to be a frequent marker of these tumors and to have diagnostic and prognostic significance. PURPOSE: We evaluated the possible association between this cytogenetic marker and clinical outcome for men with germ cell tumors. METHODS: One hundred seventy-eight germ cell tumor samples from 150 men were studied using conventional and molecular cytogenetic techniques. Of these samples, 171 were evaluable. Patient characteristics, disease stage, treatment outcome, and disease status were correlated with the observed cytogenetic changes. In addition, 28 biopsy specimens obtained from 28 patients with tumors of uncertain histogenesis were evaluated to determine whether the presence of i(12p) could serve as a diagnostic marker of a germ cell origin for these tumors. RESULTS: Of the 171 evaluable tumor accessions, 101 (59%) yielded abnormal karyotypes. i(12p) was determined to be present in 79 of the 101 (79%) abnormal karyotypes, which were derived from all cell types and primary sites. An abnormal karyotype was more frequently obtained from nonseminomatous tumors (91/137 [81%]) than from seminomas (10/34 [30%] [P < .001]). Tumors resulting in a cytogenetic failure were more likely to respond completely to chemotherapy than tumors with an abnormal karyotype (P = .004). i(12)p copy number was not associated with response or survival. Fluorescence in situ hybridization using a chromosome 12 centromere-specific probe detected i(12p) in 47 of 47 tumors (100%) already shown to have i(12p) by cytogenetic analysis and in 13 of 49 tumors (27%) exhibiting either an abnormal karyotype or a cytogenetic failure. One or more copies of i(12p), excess 12p copy number, or a deletion on the long arm of chromosome 12 was found in seven of 28 (25%) midline tumors of uncertain histogenesis, thus establishing a diagnosis of a germ cell tumor in these patients. One partial and five complete responses were observed in these seven patients. Only two partial responses were seen in the 17 patients who had no detectable germ cell tumor-related cytogenetic marker (P = .009). CONCLUSIONS: i(12p) is a highly nonrandom chromosomal marker seen in about 80% of male germ cell tumors with evaluable cytogenetic abnormalities. The presence of this isochromosome has diagnostic and possibly prognostic importance for patients with these tumors. IMPLICATIONS: Cytogenetic studies of germ cell tumors in prospective clinical treatment trials are warranted to define more precisely the relationship between histologic subtype, serum tumor marker production, and prognosis.

Adolescent↗

Effect of corticotropin releasing factor (CRF) in the median eminence on gonadotropins in ovariectomized rats with or without steroid priming: dose-response study.

We determined the dose-response relationship and examined the time related effect of CRF (corticotropin releasing factor) injected directly into the median eminence (ME) on LH and FSH secretion in conscious female rats of different steroid status. Doses of 0.25, 0.75, 1, and 1.5 nM CRF dissolved in 1 microliter of water were injected into the ME in 5 experimental groups of rats: Short-term (2 days) ovariectomized (sOVX); long-term (3-4 weeks) ovariectomized (lOVX); lOVX primed by estradiol benzoate (EB) 4 h before the experiment (lOVX+E); lOVX primed by EB 36 h before the experiment (lOVXE) and lOVX primed by EB 72 h and progesterone 6 h before experiment (lOVXP). Blood was collected at 30, 60, 90, and 120 min postinjection to determine LH and FSH by RIA. CRF at the doses of 0.75, 1, and 1.5 nM significantly decreased serum LH levels in all groups. The dose of 0.25 nM CRF was ineffective. The highest dose (1.5 nM) of CRF had no effect on serum FSH levels. The results suggest that CRF inhibits LH secretion, at least in part, by a central action of GnRH release in the ME, and that this effect is independent of the estrogen/progesterone status of the animal.

Animals↗

Single-strand conformation polymorphism analysis of human decorin, biglycan and fibromodulin cDNAs.

The coding regions of the human decorin, biglycan and fibromodulin cDNAs have been examined utilizing the method of single-strand conformation polymorphism analysis. Analysis of total RNA from a group of eight human skin fibroblast cell lines did not detect any sequence variations in the decorin cDNA. In contrast, the analysis detected three sequence variations in the biglycan cDNA and one in the fibromodulin cDNA from the same group of cell lines. For the biglycan cDNA, one variation involved a position in the 5'-untranslated region, while the other two affected the wobble bases of triples encoding serine residues 10 and 143 of the mature core protein. For the fibromodulin cDNA, the variation involved the wobble position of the codon for glutamic acid residue 61 of the putative mature core protein. Single-strand conformation polymorphism analysis of these proteoglycan cDNAs was also applied to study patients exhibiting a variety of connective tissue pathologies, including chondrodysplasia punctata, Desbuquois syndrome, Dyggve-Melchior-Clausen syndrome, dyssegmental dysplasia, Ehlers-Danlos syndrome types I and III, Ellis van Creveld syndrome and thanatophoric dysplasia, though no additional sequence variations were detected.

Base Sequence↗

The differentiation of parasitic nematodes using random amplified polymorphic DNA.

DNA from species and races of plant parasitic nematodes (Meloidogyne, Globodera and Heterodera) and a human parasitic nematode (Trichinella) were subjected to polymerase chain reaction amplification using one arbitrary primer (M-10). This technique results in relatively simple DNA profiles that include polymorphic markers known as random amplified polymorphic DNA (RAPDs). The RAPD profiles of the plant nematode species of Meloidogyne made possible the identification of M. incognita and M. hapla, but no differences were found between the patterns of M. javanica, M. arenaria and M. graminicola. Moreover, the four races of M. incognita were indistinguishable by this primer. In contrast, when races of the plant nematode Globodera rostochiensis (Ro1 and Ro2/3) were studied under the same RAPDs conditions, a race specific profile allows these two most devastating races to be differentiated. When DNAs of eight Trichinella isolates were subjected to RAPD studies, four different patterns were identified, corresponding to the four Trichinella clusters previously defined by isozyme polymorphism.

Animals↗

Importance of designated thoracic trauma surgeons in the management of traumatic aortic transection.

The medical literature is replete with reports on traumatic aortic transection. These reports have delineated many factors regarding the morbidity and high mortality of this ominous injury. Most reports are reviews of the collective experience of a single institution over a period of years. It is likely that many authors writing on the subject of traumatic aortic transection have no experience with operative repair of the lesion. There has been debate about the various techniques of primary repair versus graft insertion, as well as the question of whether cardiopulmonary bypass is superior to the "clamp and sew" methods. No studies have directly examined the skills of individual surgeons with respect to outcome. We present the results of a study from a university-affiliated level I trauma center in which the outcomes from various groups of surgeons were compared over a 5-year period. The information in this study strongly suggests that designated thoracic trauma surgeons who are promptly available and have dedicated interests in trauma patients achieve better results.

Adolescent↗

Effect of increased myocardial cyclic GMP induced by cyclic GMP-phosphodiesterase inhibition on oxygen consumption and supply of rabbit hearts.

1. We tested the hypothesis that increasing myocardial cyclic GMP levels would reduce myocardial O2 consumption and areas of low O2 supply/consumption balance, using zaprinast, a selective cyclic GMP-phosphodiesterase inhibitor. 2. The study was conducted in three groups (vehicle, 10(-3) and 3 x 10(-3) mol/L zaprinast) of anaesthetized open-chest New Zealand white rabbits (n = 24). Coronary blood flow (radioactive microspheres), arterial and venous O2 saturation (microspectrophotometry), O2 consumption, cyclic GMP content (competitive binding) and cyclic GMP-phosphodiesterase activity (conversion of 3H-cyclic GMP to 3H-GMP) were determined. 3. Agents were applied to a patch on the myocardial surface and did not cause significant haemodynamic changes, except for bradycardia in the vehicle and low dose group. 4. The total myocardial cyclic GMP-phosphodiesterase activity was 148 +/- 14 while the zaprinast (10 mumol/L) inhibitable activity averaged 63 +/- 8 pmol/mg protein per min. Cyclic GMP content was increased with increasing doses of zaprinast (vehicle, 4.308 +/- 0.349 pmol/g; low dose zaprinast, 4.803 +/- 0.279 and high dose zaprinast, 7.938 +/- 1.304 pmol/g). 5. Coronary blood flow was not different after treatment (198 +/- 11, 209 +/- 10 and 153 +/- 9 mL/min per 100 g for the vehicle, low and high dose zaprinast, respectively). 6. Under control conditions, 48% of the small veins had O2 saturations below 50%. With zaprinast, this value was reduced to 19% for the low and 24% for the high dose. 7. Average venous O2 saturation increased with zaprinast (49 +/- 2%, 61 +/- 3% and 59 +/- 1%).(ABSTRACT TRUNCATED AT 250 WORDS)

3',5'-Cyclic-GMP Phosphodiesterases↗