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Biomedical subjects

E Martinez

Publications and source records attributed to E Martinez.

At least 19 recordsLinked to original sources
PubMed1999

Comparative study of carbohydrate antigen 195 and carcinoembryonic antigen for the diagnosis of pancreatic carcinoma.

The expression CA195 in serum, defined by monoclonal antibody CC3C195 (IgM), was studied in 67 patients with pancreatic cancer and in 138 patients with biliary or pancreatic benign disease. The results were compared with carcinoembryonic antigen (CEA) expression. The overall sensitivity of the CA195 assay (> 12 U/ml) was higher than that for CEA (89.5% vs. 53.7%) (p < 0.001). Sensitivity was increased to 92.5% with the simultaneous use of the two antigens, but the difference was statistically significant only with CEA (p < 0.001). The specificity of CA195 calculated from all patients with benign diseases was lower than that of CEA (73.1% vs. 89.8%). However, using a cutoff value of 100 U/ml for CA195, the specificity of this antigen (82%) was higher than that of CEA. These results demonstrate that marked elevations of tumor antigen CA195 are relatively specific for pancreatic carcinoma, and that this antigen is superior to CEA for diagnosing pancreatic cancer by virtue of its higher sensitivity.

Antibodies, Monoclonal↗
PubMed1999

Renal artery stenosis treated with stent deployment: indications, technique, and outcome for 108 patients.

From January 1993 to May 1996, 108 patients (64 men, 44 women; mean age, 72 years; age range, 37 to 87 years) underwent 125 percutaneous transluminal angioplasties and stent implantations primarily for atherosclerotic lesions of the renal artery. Sixty-four patients underwent treatment for renovascular hypertension (two antihypertensive medications or more), 32 patients underwent treatment for a combination of hypertension and renal failure (serum creatinine level >/=1.6 mg/dL), and a small group of six patients (5%) without hypertension or diminished renal function underwent treatment to prevent the progression to renal artery occlusion and kidney loss. Thirty-three patients (31%) had renovascular hypertension that was classified as severe on three or more medications, 31 patients (29%) had renovascular hypertension that was classified as moderate on two medications, and 38 patients (35%) had renovascular hypertension that was classified in the mild group on a single antihypertensive agent. Stenotic lesions were located at the ostium of the renal artery in 82 cases (65%) and were ostial-adjacent (<5 mm from renal ostium) in the other 43 cases (34%). A total of 125 stents were deployed in 125 arteries (procedural success 97.6%). Renovascular hypertension either was cured or was improved in 73 patients (68%), with 14 patients (13%) considered cured (normotensive on no medications). The conditions of 29 patients (27%) were unchanged, and 6 patients (5%) had worsening hypertension after surgery. We were unable to demonstrate a statistically significant improvement in serum creatinine levels after renal artery balloon angioplasty/stenting. Complications occurred in a total of nine cases (7.2%), six of which were related to technical problems. One patient had worsening renal insufficiency caused by contrast agent, and another patient had a perinephric hematoma develop that necessitated evacuation. There were four postoperative deaths (30-day mortality). Two of these deaths were caused by postoperative myocardial infarction. The other two patients had progressive renal failure develop that necessitated dialysis. These patients later died of the disease process despite supportive care. Follow-up renal artery duplex scan studies and angiograms were available on 96 patients (76%). The mean peak systolic renal/aortic ratio on duplex scanning was 2.2. Life-table analysis yielded a 74% primary patency rate and an 85% secondary patency rate at 36 months. This retrospective analysis showed the effectiveness of combining percutaneous transluminal angioplasty with stent deployment for significant renal artery stenosis to treat renovascular hypertension.

Adult↗
PubMed1999

A novel human SRB/MED-containing cofactor complex, SMCC, involved in transcription regulation.

A novel human complex that can either repress activator-dependent transcription mediated by PC4, or, at limiting TFIIH, act synergistically with PC4 to enhance activator-dependent transcription has been purified. This complex contains homologs of a subset of yeast mediator/holoenzyme components (including SRB7, SRB10, SRB11, MED6, and RGR1), homologs of other yeast transcriptional regulatory factors (SOH1 and NUT2), and, significantly, some components (TRAP220, TRAP170/hRGR1, and TRAP100) of a human thyroid hormone receptor-associated coactivator complex. The complex shows direct activator interactions but, unlike yeast mediator, can act independently of the RNA polymerase II CTD. These findings demonstrate both positive and negative functional capabilities for the human complex, emphasize novel (CTD-independent) regulatory mechanisms, and link the complex to other human coactivator complexes.

Cloning, Molecular↗
PubMed1999

The prepropeptide of vacuolar aminopeptidase I is necessary and sufficient to target the fluorescent reporter protein GFP to the vacuole of yeast by the Ccvt pathway.

We have studied the capacity of the prepro amino extension of vacuolar protease leucine aminopeptidase I (API) to target the fluorescent reporter protein GFP to the vacuole of yeast. The preproGFP chimera constructed by extending the amino end of GFP with the prepro-part of API is rapidly degraded in both wild-type WCG cells and WCG 11/21a cells deficient in the proteasome. In contrast, the chimera expressed in WCG-PP cells deficient in both proteasome activity and vacuolar proteinase A accumulates in the vacuole, where it remains stable. Replacement of Gly by Ile-7, a substitution that prevents folding of the pre-part into an amphipathic helix and inhibits the targeting of the API precursor to the vacuole, inhibits the targeting of preproGFP to the vacuole. The separated pre- and pro-parts of the API precursor do not target GFP to the vacuole. Targeting of preproGFP to the vacuole is independent of its levels of expression, as the fluorescent protein localizes to the vacuole in cells expressing the protein under the control of both the GAL 1/10 or the API promoter. The preproGFP expressed under both promoters is recovered as monomers from cytosolic cell extracts. PreproGFP expressed under the API promoter is packed into cytoplasmic bodies that penetrate into the vacuolar lumen to release the protein. Altogether our results show that the prepro-part of the API precursor is necessary and sufficient to target the green fluorescent reporter protein to the vacuole.

Amino Acid Substitution↗
PubMed1999

Length variation of helix III in a hammerhead ribozyme and its influence on cleavage activity.

The previously described HIV-1 directed hammerhead ribozyme 2as-Rz12 can form with its target RNA 2s helices I and III of 128 and 278 base pairs (bp). A series of derivatives was made in which helix III was truncated to 8, 5, 4, 3, and 2 nucleotides (nt). These asymmetric hammerhead ribozymes were tested for in vitro cleavage and for inhibition of HIV-1 replication in human cells. Truncation of helix III to 8 bp did not affect the in vitro cleavage potential of the parental catalytic antisense RNA 2as-Rz12. Further truncation of helix III led to decreased cleavage rates, with no measurable cleavage activity for the 2 bp construct. All catalytically active constructs showed complex cleavage kinetics. Three kinetic subpopulations of ribozyme-substrate complexes could be discriminated that were cleaved with fast or slow rates or not at all. Gel purification of preformed ribozyme-substrate complexes led to a significant increase in cleavage rates. However, the complex cleavage pattern remained. In mammalian cells, the helix III-truncated constructs showed the same but no increased inhibitory effect of the comparable antisense RNA on HIV-1 replication.

Animals↗
PubMed1999

Children with cystic fibrosis benefit from massage therapy.

OBJECTIVE: To measure the effects of parents giving massage therapy to their children with cystic fibrosis to reduce anxiety in parents and their children and to improve the children's mood and peak air flow readings. METHODS: Twenty children (5-12 years old) with cystic fibrosis and their parents were randomly assigned to a massage therapy or a reading control group. Parents in the treatment group were instructed and asked to conduct a 20-minute child massage every night at bedtime for one month. Parents in the reading control group were instructed to read for 20 minutes a night with their child for one month. On days 1 and 30, parents and children answered questions relating to present anxiety levels and children answered questions relating to mood, and their peak air flow was measured. RESULTS: Following the first and last massage session, children and parents reported reduced anxiety. Mood and peak air flow readings also improved for children in the massage therapy group. CONCLUSIONS: These findings suggest that parents may reduce anxiety levels by massaging their children with cystic fibrosis and their children may benefit from receiving massage by having less anxiety and improved mood, which in turn may facilitate breathing.

Analysis of Variance↗
PubMed1999

Pregnant rat uterus expresses high levels of the type 3 iodothyronine deiodinase.

Although thyroid hormones are critically important for the coordination of morphogenic processes in the fetus and neonate, premature exposure of the embryo to levels of the hormones present in the adult is detrimental and can result in growth retardation, malformations, and even death. We report here that the pregnant rat uterus expresses extremely high levels of the type 3 iodothyronine deiodinase (D3), which inactivates thyroxine and 3,3', 5-triiodothyronine by 5-deiodination. Both D3 mRNA and activity were present at the implantation site as early as gestational day 9 (E9), when expression was localized using in situ hybridization to uterine mesometrial and antimesometrial decidual tissue. At later stages of gestation, uterine D3 activity remained very high, and the levels exceeded those observed in the placenta and in fetal tissues. After days E12 and E13, as decidual tissues regressed, D3 expression became localized to the epithelial cells lining the recanalized uterine lumen that surrounds the fetal cavity. These findings strongly suggest that the pregnant uterus, in addition to the placenta, plays a critical role in determining the level of exposure of the fetus to maternal thyroid hormones.

Animals↗
PubMed1999

Synthesis and hypolipidaemic evaluation of a series of alpha-asarone analogues related to clofibrate in mice.

A series of alpha-asarone analogues related to clofibrate, containing an acetic acid group at C-2 of the aromatic ring, has been prepared as the acids or as the ethyl and methyl esters. The corresponding alcohols were also synthesized by reduction of the ethyl esters. The compounds were examined in hyperlipidaemic male mice to evaluate their ability to modify serum lipoprotein cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglycerides after oral administration of 40 and 80 mg kg(-1) for 6 days. Except for methyl 2-methoxy-5-nitro-4-(2-propenyl)phenoxyacetate at either dose, these clofibrate-related phenoxyacetic acid derivatives were found to have significant hypocholesterolaemic activity. Levels of low-density lipoprotein cholesterol and triglycerides were significantly reduced and those of high-density lipoprotein cholesterol were elevated. 2-Methoxy-5-nitro-4-(2-propenyl)phenoxyacetic acid was active at both doses in all the tests. Clofibrate (150 mg kg(-1)) was more potent at reducing low-density lipoprotein cholesterol. No activity was detected for the alcohol derivatives. These preliminary results suggest that this class of compound might have more promise as potential hypolipidaemic agents than other alpha-asarone derivatives. Further investigation and characterization should be performed to determine the mode of action of these agents on lipid metabolism.

Allylbenzene Derivatives↗
PubMed1998

A human SPT3-TAFII31-GCN5-L acetylase complex distinct from transcription factor IID.

In yeast, SPT3 is a component of the multiprotein SPT-ADA-GCN5 acetyltransferase (SAGA) complex that integrates proteins with transcription coactivator/adaptor functions (ADAs and GCN5), histone acetyltransferase activity (GCN5), and core promoter-selective functions (SPTs) involving interactions with the TATA-binding protein (TBP). In particular, yeast SPT3 has been shown to interact directly with TBP. Here we report the molecular cloning of a cDNA encoding a human homologue of yeast SPT3. Amino acid sequence comparisons between human SPT3 (hSPT3) and its counterparts in different yeast species reveal three highly conserved domains, with the most conserved 92-amino acid N-terminal domain being 25% identical with human TAFII18. Despite the significant sequence similarity with TAFII18, native hSPT3 is not a bona fide TAFII because it is not associated in vivo either with human TBP/TFIID or with a TFIID-related TBP-free TAFII complex. However, we present evidence that hSPT3 is associated in vivo with TAFII31 and the recently described longer form of human GCN5 (hGCN5-L) in a novel human complex that has histone acetyltransferase activity. We propose that the human SPT3-TAFII31-GCN5-L acetyltransferase (STAGA) complex is a likely homologue of the yeast SAGA complex.

Acetyltransferases↗
PubMed1998

The Nuclear Receptor Resource: a growing family.

Last year, the original Glucocorticoid Receptor Resource was expanded into a comprehensive project: the Nuclear Receptor Resource (NRR, http:// nrr.georgetown.edu/nrr/nrr.html ). The NRR has since been offering comprehensive information on nuclear receptor structure and function, as well as general facts of interest to the scientific community on meetings, funding and employment opportunities. The project now includes individual resources as part of a network which integrates information on glucocorticoid, androgen, mineralocorticoid, thyroid hormone, Vitamin D and peroxisome-proliferator activated receptors. Many investigators have joined the NRR network by filling the Who is who? form available in the NRR home page. This has facilitated communication among scientists in the field and dissemination of data nor otherwise published. Because several investigators have contacted NRR authors over the past few months asking for advice and materials for educational purposes, we have recently decided to include in our project an educational resource on nuclear receptors termed the 'Graphics Library'. The input and suggestions of NRR users do shape the future direction of the project, so we encourage user to give us feedback.

Computer Communication Networks↗
PubMed1998

Children with asthma have improved pulmonary functions after massage therapy.

Thirty-two children with asthma (16 4- to 8-year-olds and 16 9- to 14-year-olds) were randomly assigned to receive either massage therapy or relaxation therapy. The children's parents were taught to provide one therapy or the other for 20 minutes before bedtime each night for 30 days. The younger children who received massage therapy showed an immediate decrease in behavioral anxiety and cortisol levels after massage. Also, their attitude toward asthma and their peak air flow and other pulmonary functions improved over the course of the study. The older children who received massage therapy reported lower anxiety after the massage. Their attitude toward asthma also improved over the study, but only one measure of pulmonary function (forced expiratory flow 25% to 75%) improved. The reason for the smaller therapeutic benefit in the older children is unknown; however, it appears that daily massage improves airway caliber and control of asthma.

Adolescent↗
PubMed1998

Peripheral intrahepatic cholangiocarcinoma: ultrasound findings and differential diagnosis from hepatocellular carcinoma.

OBJECTIVE: Peripheral cholangiocarcinoma may be more frequent than expected, and is usually asymptomatic until it is well advanced. Our purpose was to assess the accuracy of ultrasound in differential diagnosis. METHODS: We compared the sonographic findings of ten consecutive patients with histologically proven peripheral cholangiocarcinoma with those obtained in 26 consecutive patients with hepatocarcinoma detected in the same period. In every patient we performed an ultrasound-guided biopsy with a fine (22 gauge) cutting needle. RESULTS: In all patients with a final diagnosis of peripheral cholangiocarcinoma, the ultrasound scan disclosed multiple well-defined nodules with a hypoechoic or target pattern. Two patients had dilated intrahepatic bile ducts and suspected infiltration of the common duct. No patient had ascites. Only minimal alterations in laboratory examinations were found. Ultrasound-guided fine cutting needle biopsy yielded diagnostic material and allowed the definitive differential diagnosis. CONCLUSION: Peripheral cholangiocarcinoma even in Western countries may represent a significant proportion of all primary liver cancers. Due to non-specific symptomatology only intractable and far advanced cases were detected by means of sonography. Ultrasound findings did not differ from those found in cases of metastases from extrahepatic adenocarcinomas or hepatocarcinoma with multinodular pattern (10/26 in our series).

Bile Duct Neoplasms↗
PubMed1998

Functional and biochemical evidence for diazepam as a cyclic nucleotide phosphodiesterase type 4 inhibitor.

1. The responses of the electrically-driven right ventricle strip of the guinea-pig heart to diazepam were recorded in the absence and in the presence of different selective cyclic nucleotide phosphodiesterase (PDE) inhibitors. 2. Diazepam, at concentrations ranging from 1 microM to 100 microM, was devoid of effect on the contractile force in this preparation. 3. Conversely, diazepam (5 microM-100 microM) produced a consistent positive inotropic response in the presence of a concentration (1 microM), that was without effect in the absence of diazepam, of either of the selective PDE 3 inhibitors milrinone or SK&F 94120, but not in the presence of the selective PDE 4 inhibitor rolipram. 4. This effect of diazepam was not gamma-aminobutyric acid (GABA)-dependent, since it was neither mimicked nor potentiated by GABA, and was not affected by either a high concentration (5 microM) of the antagonists of the benzodiazepine/GABA/channel chloride receptor complex, picrotoxin, flumazenil and beta-carboline-3-carboxylic acid methyl ester (betaCCMe), or by the inverse agonists, beta-carboline-3-carboxylic acid N-methylamide (betaCCMa) and methyl 6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM, 0.1 microM). Furthermore, a specific antagonist of the peripheral benzodiazepine receptors, PK 11195 (5 microM), did not influence the effect of diazepam. 5. Biochemical studies with isolated PDEs, confirmed that diazepam selectively inhibits type 4 PDE from guinea-pig right ventricle rather than the other PDEs present in that tissue. The compound inhibited this enzyme in a non-competitive manner. Diazepam was also able to inhibit PDE 5, the cyclic GMP specific PDE absent from cardiac muscle, with a potency close to that shown for PDE 4. 6. Diazepam displaced the selective type 4 PDE inhibitor, rolipram from its high affinity binding site in rat brain cortex membranes, and also potentiated the rise in cyclic AMP levels induced by isoprenaline in guinea-pig eosinophils, where only type 4 PDE is present. 7. The PDE inhibitory properties of diazepam were shared, although with lower potency, by other structurally-related benzodiazepines, that also displaced [3H]-rolipram from its high affinity binding site. The order of potency found for these compounds in these assays was not related to their potencies as modulators of the GABA receptor through its benzodiazepine binding site. 8. The pharmacological and biochemical data presented in this study indicate that diazepam behaves as a selective type 4 PDE inhibitor in cardiac tissue and this effect seems neither to be mediated by the benzodiazepine/GABA/channel chloride receptor complex nor by peripheral type benzodiazepine receptors.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1998

Morphometrics of domestic Panstrongylus rufotuberculatus in Bolivia.

The trend to domesticity in Triatominae may represent a transitionary phase, towards increasing vectorial importance in the transmission of Chagas disease to humans, and requires sustained entomological surveillance. Although generally considered a sylvatic species, Panstrongylus rufotuberculatus has been recently captured inside human dwellings in the provinces of Nor Yungas and Muñecas in the Department of La Paz, Bolivia, providing evidence of this species' ability to colonise domestic habitats. The results of previous research on domestic and sylvatic specimens of other species of Triatominae indicate that morphometrics could be used to monitor this adaptive process. The most likely cause of differences seen in the size and shape of bugs from domestic colonies of P. rufotuberculatus from two neighbouring villages in Bolivia is probably genetic drift rather than environmental influences. Comparison with allopatric sylvatic specimens, including the holotype of P. rufatuberculatus, showed a general reduction in size from sylvatic to domestic specimens.

Animals↗
PubMed1998

Novel cofactors and TFIIA mediate functional core promoter selectivity by the human TAFII150-containing TFIID complex.

TATA-binding protein-associated factors (TAFIIs) within TFIID control differential gene transcription through interactions with both activators and core promoter elements. In particular, TAFII150 contributes to initiator-dependent transcription through an unknown mechanism. Here, we address whether TAFIIs within TFIID are sufficient, in conjunction with highly purified general transcription factors (GTFs), for differential core promoter-dependent transcription by RNA polymerase II and whether additional cofactors are required. We identify the human homologue of Drosophila TAFII150 through cognate cDNA cloning and show that it is a tightly associated component of human TFIID. More importantly, we demonstrate that the human TAFII150-containing TFIID complex is not sufficient, in the context of all purified GTFs and RNA polymerase II, to mediate transcription synergism between TATA and initiator elements and initiator-directed transcription from a TAFII-dependent TATA-less promoter. Therefore, TAFII-promoter interactions are not sufficient for the productive core promoter-selective functions of TFIID. Consistent with this finding, we have partially purified novel cofactor activities (TICs) that potentiate the TAFII-mediated synergism between TATA and initiator elements (TIC-1) and TAFII-dependent transcription from TATA-less promoters (TIC-2 and -3). Furthermore, we demonstrate an essential function for TFIIA in TIC- and TAFII-dependent basal transcription from a TATA-less promoter. Our results reveal a parallel between the basal transcription activity of TAFIIs through core promoter elements and TAFII-dependent activator function.

ARNTL Transcription Factors↗