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Biomedical subjects

A Martinez

Publications and source records attributed to A Martinez.

At least 145 records · Page 8Linked to original sources

Risk analysis of the thermal sterilization process. Analysis of factors affecting the thermal resistance of microorganisms.

A risk analysis was applied to experimental heat resistance data. This analysis is an approach for processing experimental thermobacteriological data in order to study the variability of D and z values of target microorganisms depending on the deviations range of environmental factors, to determine the critical factors and to specify their critical tolerance. This analysis is based on sets of sensitivity functions applied to a specific case of experimental data related to the thermoresistance of Clostridium sporogenes and Bacillus stearothermophilus spores. The effect of the following factors was analyzed: the type of target microorganism; nature of the heating substrate; pH, temperature; type of acid employed and NaCl concentration. The type of target microorganism to be inactivated, the nature of the substrate (reference or real food) and the heating temperature were identified as critical factors, determining about 90% of the alteration of the microbiological risk. The effect of the type of acid used for the acidification of products and the concentration of NaCl can be assumed to be negligible factors for the purposes of engineering calculations. The critical non-uniformity in temperature during thermobacteriological studies was set as 0.5% and the critical tolerances of pH value and NaCl concentration were 5%. These results are related to a specific case study, for that reason their direct generalization is not correct.

Citric Acid↗

Cardiovascular effects of captopril and enalapril in obese Zucker rats.

The effects of two weeks of oral administration of the angiotensin-converting enzyme inhibitors captopril (a sulphydryl-containing drug) and enalapril (which lacks the sulphydryl group) on skeletal muscle glucose uptake, arterial blood pressure, cardiac hypertrophy, proteinuria and aortic vascular reactivity in obese Zucker rats were evaluated. Captopril (50 mg kg(-1) once daily) and enalapril (10 mg kg(-1) did not modify body weight gain or food or water intake. Both drugs decreased systolic blood pressure (157+/-6, 133+/-4 and 136+/-3 mm Hg, in vehicle-, captopril- and enalapril-treated rats, respectively), blood glucose (172+/-8 vs. 151+/-7 and 158+/-5 mg dl(-1), respectively), proteinuria (46+/-10 vs. 17+/-2 and 18+/-2.5 mg dl(-1), respectively) and heart weight (2.17+/-0.03, 1.98+/-0.02 and 1.99+/-0.04 mg g(-1)of body weight, respectively). Plasma insulin concentration was significantly increased by enalapril (17+/-2 ng ml(-1) vs. 9+/-2) but not by captopril (12+/-1). In the absence of insulin, the diaphragms from captopril- or enalapril-treated rats showed a significantly higher glucose uptake than that of controls (31% and 30% vs. control group, respectively). The presence of insulin in the incubation medium did not stimulate peripheral glucose uptake in the control group but significantly increased glucose uptake in diaphragms from captopril- or enalapril-treated rats (enhancement of glucose uptake vs. control: 52% and 43%, respectively). Endothelium-intact aortic rings from control Zucker rats showed a poor relaxant response to acetylcholine (maximal relaxation of 38.4+/-4.7%). Captopril significantly improved the endothelium-dependent vascular relaxation responses to acetylcholine and the endothelium-independent relaxation to the nitric oxide donor sodium nitroprusside whereas enalapril did not modify these relaxant responses. Neither captopril nor enalapril significantly affected the vascular contractile responses to the vasoconstrictors noradrenaline or KCl. In conclusion, the angiotensin-converting enzyme inhibitors captopril and enalapril reversed insulin resistance and the associated cardiovascular complications (cardiac hypertrophy, hypertension and proteinuria) in the obese Zucker rat, an animal model of non-insulin-dependent (type II) diabetes mellitus. However, only captopril, but not enalapril, improved the impaired endothelium-dependent and independent relaxant responses in the isolated rat aorta.

Acetylcholine↗

Irradiation of the tumor bed alone after lumpectomy in selected patients with early-stage breast cancer treated with breast conserving therapy.

BACKGROUNDS AND OBJECTIVES: We present the interim findings of our in-house protocol treating the tumor bed alone after lumpectomy with low-dose-rate (LDR) interstitial brachytherapy in selected patients with early-stage breast cancer treated with breast conserving therapy (BCT). METHODS: From 1 March 1993 through 1 January 1995, 50 women with early-stage breast cancer were entered into a protocol of tumor bed irradiation alone using an interstitial LDR implant. Patients were eligible if their tumor was an infiltrating ductal carcinoma < or =3 cm in diameter, surgical margins were clear by at least 2 mm, the tumor did not contain an extensive intraductal component, the axilla was surgically staged with < or =3 nodes involved with cancer, and a postoperative mammogram was performed. Implants were positioned using a template guide delivering 50 Gy over 96 hr to the lumpectomy bed plus a 1-2-cm margin. Local control, cosmetic outcome, and complications were assessed. RESULTS: Patients ranged in age from 40 to 84 years (median, 65). The median tumor size was 10 mm (range, 1-25). Seventeen of 50 patients (34%) had well-differentiated tumors, 22 (44%) had moderately differentiated tumors, and in 11 (22%) the tumor was poorly differentiated. Forty-five patients (90%) were node-negative while five (10%) had 1-3 positive nodes. A total of 23 (46%) patients were placed on tamoxifen and 3 (6%) received adjuvant systemic chemotherapy. No patient was lost to follow-up. The median follow-up for surviving patients is 47 months (range, 37-59). No patient has experienced a local, regional, or distant failure. Three patients have died at 19, 33, and 39 months after treatment. All were without clinical evidence of recurrent disease and all deaths were unrelated to treatment. Good-to-excellent cosmetic results have been observed in 49 of 50 patients (98%) (median cosmetic follow-up was 44 months with a range of 19-59). No patient has experienced significant sequelae related to their implant. CONCLUSIONS: Interim results with treatment of the tumor bed alone with an LDR interstitial implant appear promising. Long-term follow-up of these patients and additional studies will be necessary to establish the equivalence of this treatment approach compared to standard BCT.

Adult↗

Creation of ecdysone receptor chimeras in plants for controlled regulation of gene expression.

Transformation with a chimeric receptor containing the glucocorticoid transactivation and DNA-binding domains fused to an ecdysteroid receptor ligand-binding domain permits ecdysone agonist-inducible gene expression in monocotyledonous plant cells. The inducible system is based on the specific activation of a chimeric receptor containing the ligand-binding domain of the Heliothis virescens ecdysteroid receptor and the inducer RH5992 (a 20-hydroxyecdysone agonist). RH5992 is an non-steroidal agrochemical with a high specificity for lepidopteran ecdysone receptors. Addition of RH5992 to transformed cells results in high levels of inducible expression in a ligand-specific manner, particularly when the effector receptor is coupled to the strong transactivator VP16. A chimeric construct containing the Drosophila ecdysone ligand-binding domain failed to activate reporter gene activity with RH5992, while activation was observed in the presence of muristeroneA. The system described provides the basis for an inducible gene expression system that is compatible with agricultural use.

Chimera↗

Transcriptional activation of the cloned Heliothis virescens (Lepidoptera) ecdysone receptor (HvEcR) by muristeroneA.

Ecdysteroids play an important role during insect development. We report here the isolation and characterisation of an Ecdysone receptor (EcR) homologue from Heliothis virescens (HvEcR) and present evidence supporting the HvEcR active role as an active component of the native insect receptor. Alignment of the deduced amino acid sequence of HvEcR with those of EcRs from other species confirmed its membership of this family and showed that it is closely related to the B1 isoform of Drosophila melanogaster. Northern blot analysis showed that two transcripts (6.0 and 6.5 kb) were recognised by a probe spanning the DNA and ligand binding domains of the HvEcR. Genomic Southern blots showed that the HvEcR is encoded by a single copy gene. Two lines of evidence towards the functional activity of the HvEcR are presented. In vitro transcribed and translated HvEcR showed specific binding to hsp27 and pall response elements in the presence of CfUSP. Stable expression of HvEcR in 293 cells induced reporter gene activity in the presence of muristeroneA in a dose dependant manner while dexamethasone failed to activate.

ATP-Binding Cassette Transporters↗

Prevalence of temporomandibular joint disk displacement in infants and young children.

OBJECTIVE: The purpose of this study was to determine the prevalence of temporomandibular joint disk displacement in infants and young children. STUDY DESIGN: Magnetic resonance images were obtained of the temporomandibular joints in 30 infants and young children ranging in age from 2 months to 5 years (median age, 3 years; mean age, 2.5 years). RESULTS: All joints had normal superior disk position. The computed 95% confidence interval was 0.00-0.06, which implies a minimal probability that disk displacement would occur in this age group. CONCLUSIONS: The result contradicts previous suggestions that temporomandibular joint disk displacement could represent a congenital normal anatomic variant.

Argentina↗

A compartmental analysis of the pharmacokinetics of propofol in sheep.

Conventional compartmental pharmacokinetic analysis may provide inaccurate prediction of drug concentrations after rapid i.v. administration. To examine this, compartment and effect compartment analysis was applied to measured arterial and brain concentrations of propofol in sheep after i.v. administration at a range of doses and dose rates. Although arterial and brain concentrations were reasonably well fitted to compartmental and effect compartment models for individual doses and dose rates, the structure and parameters of all models differed with changes in both dose and rate of administration. There were large discrepancies between predicted and measured arterial and brain concentrations when these models were used to predict drug concentrations across doses and dose rates. These data support the limitations of this type of modeling in the setting of rapid propofol administration.

Anesthetics, Intravenous↗

Amino acid polymorphism at residue 71 in HLA-DR beta chain plays a critical role in susceptibility to ulcerative colitis.

The association of ulcerative colitis with distinct HLA-DRB1 alleles has not been easy to ascertain. Recent studies show that among HLA-DR2 alleles, DRB1*15 but not DRB1*16, is associated with the disease. Similarly, in the HLA-DR1 group, only DRB1*0103 is increased in ulcerative colitis patients. The aim of our study was to identify critical DRB1 residues that might account for these differences. We typed 121 patients with ulcerative colitis and 275 controls using gene amplification and sequence-specific oligonucleotide probing for HLA-DRB1 and DRB3. We observed a strong negative association between HLA-DRB1 alleles that encode lysine at position 71 in their beta-chain and susceptibility to ulcerative colitis. Differences in the prevalence among other alleles differing only in the third hypervariable region suggested a hierarchy of susceptible and protective class II alleles related to the presence of an acidic, neutral, or basic amino acid residue at position 71. These data implicate most strongly the amino acid residues in the third hypervariable region of the DRbeta chain, especially DRbeta71, in the association between ulcerative colitis and HLA. However, this does not exclude the contribution of other parts of the molecule and other immunoregulatory genes.

Adult↗

Prolonged dysequilibrium between blood and brain concentrations of propofol during infusions in sheep.

BACKGROUND: Previous work had shown dysequilibrium between the arterial blood and brain concentrations of the intravenous anaesthetic agent propofol following its rapid administration over 2 min to sheep. The extent of dysequilibrium was examined following slower administration as a constant rate 45-min infusion (10 mg/min). METHODS: Six sheep were prepared with arterial and sagittal sinus (effluent from the brain) blood sampling catheters and a Doppler flow probe for measuring an index of cerebral blood flow. Propofol concentrations in arterial and sagittal sinus blood during and after the infusions were measured using high-performance liquid chromatography with fluorescence detection. Brain concentrations were calculated from these concentrations and cerebral blood flow using direct mass balance methods. RESULTS: There was dysequilibrium between the arterial blood and brain concentrations until approximately 30 min after the start of the infusion, with marked hysteresis between the arterial blood and brain concentrations for the duration of the study. The equilibrium half-life between the blood and the brain was 3.5 min, which is comparable to the value of 4.3 min derived from the earlier rapid administration data, suggesting there was no time dependency in the kinetics of cerebral uptake. The mass of propofol entering the brain via arterial blood was the same as the mass leaving the brain via sagittal sinus blood, suggesting minimal metabolism of propofol in the brain of sheep. CONCLUSION: It is clear that pharmacokinetic analysis based on arterial blood concentrations alone cannot accurately account for the concentrations of propofol at its site of action in the brain.

Anesthetics, Intravenous↗

An association between viral genes and human oncogenic alterations: the adenovirus E1A induces the Ewing tumor fusion transcript EWS-FLI1.

Malignant transformation of human cells requires the accumulation of multiple genetic alterations, such as the activation of oncogenes and loss of function of tumor suppressor genes or those related to genomic instability. Among the genetic alterations most frequently found in human tumors are chromosomal translocations that may result in the expression of chimeric products with transforming capability or are able to change the expression of oncogenes. We show here that the adenovirus early region 1A (E1A) gene can induce a specific human fusion transcript (EWS-FLI1) that is characteristic of Ewing tumors. This fusion transcript was detected by RT-PCR in normal human fibroblasts and keratinocytes after expression of the adenovirus E1A gene, as well as in human cell lines immortalized by adenoviruses. Cloning and sequencing of the RT-PCR product showed fusion points between EWS and FLI1 cDNA identical to those detected in Ewing tumors. In addition, we detected a chimeric protein by western blot analysis and immunoprecipitation and a t(11,22) by fluorescent in situ hybridization. This association between a single viral gene and a specific human fusion transcript indicates a direct link between viral genes and chromosome translocations, one of the hallmarks of many human tumors.

Adenovirus E1A Proteins↗

HLA class II homozygosity confers susceptibility to common variable immunodeficiency (CVID).

Most cases of CVID occur sporadically, but familial cases do also occur and 15% of the patients with the disease have first degree relatives with IgA deficiency (IgAD). Our purpose was to study CVID association with HLA class II alleles and to ascertain whether this disease shares a common genetic background with IgAD in our population. Patients with CVID (n = 42), were typed using gene amplification and sequence-specific oligonucleotide probing for HLA-DRB1, DRB3, DQA1 and DQB1 loci and their typing compared with that of 96 IgAD and 334 healthy controls. We observed a positive association between non-Asp residues at position 57 of the HLA-DQbeta chain and CVID, although much weaker than in IgAD. Further, we found an association between CVID and homozygosity for genes encoding HLA class II molecules, especially HLA-DQ, not seen in IgAD. The data support the hypothesis that a restricted diversity of HLA class II molecules may contribute to susceptibility to CVID.

Alleles↗

Ecdysone agonist inducible transcription in transgenic tobacco plants.

A novel chemical-induced gene regulatory system for plants consisting of two molecular components is described. The first, or regulatory, cassette comprises a chimeric receptor composed of the hinge and ligand binding domains of the Heliothis virescens ecdysone receptor and the transactivation domain of the Herpes simplex VP16 protein fused to the DNA binding domain and transactivation of a mammalian glucocorticoid receptor. The second component, a reporter cassette, contains six copies of the glucocorticoid response element (GRE) fused to the minimal 35SCaMV promoter and beta-glucuronidase. The system uses a commercially available non-steroidal ecdysone agonist, RH5992 (tebufenozide), as an inducer. Activation of gene expression is shown in both tobacco transient protoplasts and transgenic plants. The response is ligand dependent and is modulated by the change in minimal promoter context. The system is capable of inducing transgene activity up to 420-fold corresponding to 150% of the activity observed with positive controls (35SCaMV:GUS).

Base Sequence↗

Semantic integration in reading: engagement of the right hemisphere during discourse processing.

We examined the brain areas involved in discourse processing by using functional MRI in 10 individuals as they read paragraphs, with or without a title, word by word for comprehension. Functional data were collected from 20 adjacent 5 mm axial slices. Discourse processing was associated with activation in inferior frontal and temporal regions of both cerebral hemispheres in the titled and untitled conditions. Moreover, there was substantially more right hemisphere activation for untitled than for the titled paragraphs. More specifically we found: (i) greater activation in the inferior temporal sulcus of both hemispheres for untitled than titled paragraphs; (ii) greater average volume of activation in response to untitled than titled paragraphs in the middle temporal sulcus of the right hemisphere and the reverse pattern in the left middle temporal sulcus. Consistent with previous studies of individuals with right hemisphere damage, we suggest that the right middle temporal regions may be especially important for integrative processes needed to achieve global coherence during discourse processing.

Adult↗

Acute and nongenomic effects of testosterone on isolated and perfused rat heart.

Gonadal steroid hormones influence vascular tone and the development of hypertension. There are sex differences in the incidence of cardiovascular diseases, and great attention has been placed on the study of estrogen cardiovascular effects. However, there are only a few reports on the effects of testosterone on the vasculature. It is commonly accepted that the mechanism of the action of steroid hormones on target tissues is mediated through the binding of hormones to cytoplasmic or nuclear receptors. However, some studies indicate that steroid action can be extremely rapid and therefore unlikely to be through a genomic mechanism. The purpose of this study was to assess the effect of intravascularly confined testosterone on an isolated rat heart to demonstrate acute and possibly nongenomic effects of the steroid. Our results show that testosterone blocked the adenosine vasodilator effect and increased vascular resistance, even when its presence was restricted to the coronary vascular lumen. These effects were exerted rapidly and possibly through nongenomic mechanisms.

Adenosine↗

Chromosomal integration of heterologous DNA in Escherichia coli with precise removal of markers and replicons used during construction.

A set of vectors which facilitates the sequential integration of new functions into the Escherichia coli chromosome by homologous recombination has been developed. These vectors are based on plasmids described by Posfai et al. (J. Bacteriol. 179:4426-4428, 1997) which contain conditional replicons (pSC101 or R6K), a choice of three selectable markers (ampicillin, chloramphenicol, or kanamycin), and a single FRT site. The modified vectors contain two FRT sites which bracket a modified multiple cloning region for DNA insertion. After integration, a helper plasmid expressing the flippase (FLP) recombinase allows precise in vivo excision of the replicon and the marker used for selection. Sites are also available for temporary insertion of additional functions which can be subsequently deleted with the replicon. Only the DNA inserted into the multiple cloning sites (passenger genes and homologous fragment for targeting) and a single FRT site (68 bp) remain in the chromosome after excision. The utility of these vectors was demonstrated by integrating Zymomonas mobilis genes encoding the ethanol pathway behind the native chromosomal adhE gene in strains of E. coli K-12 and E. coli B. With these vectors, a single antibiotic selection system can be used repeatedly for the successive improvement of E. coli strains with precise deletion of extraneous genes used during construction.

Anti-Bacterial Agents↗