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Biomedical subjects

A Muñoz

Publications and source records attributed to A Muñoz.

At least 289 records · Page 16Linked to original sources
PubMed1996

Variability of molecular biomarker measurements from nonlinear calibration curves.

In any immunoassay experiment for the detection of molecular biomarkers, a nonlinear calibration curve is constructed to relate fixed biomarker concentrations to observed tracer levels. The biomarker concentration in an experimental sample can then be estimated by projecting the experimental tracer measurements through the inverse of the calibration curve. Once an estimate of the biomarker level has been calculated, it is often of interest to determine its variability. Typically, methods for estimating this variability assume that the biomarker variability is due solely to the uncertainty in the estimation of the calibration curve. A more complete analysis would combine this uncertainty with the variability in the processing and measurements of the sample, including, e.g., measurement error of laboratory procedures or variation in enzymatic activity in enzyme-linked immunosorbent assays or radioactivity counts in RIAs. In this paper, we present a method of estimating the variability of inverse estimates assuming there is variation arising from both the determination of the calibration curve and from the preparation and measurement of the experimental sample. Our method uses a resampling algorithm that avoids requiring many distributional assumptions present in alternative procedures, can be easily implemented, and is generalizable to any immunoassay procedure. Methods for incorporating our results in the estimation of variability for planning and analyzing biomarker experiments are discussed. We provide an example using RIA data for aflatoxin B1 detection. These biomarkers for aflatoxin exposure are used in the analysis of serum aflatoxin adduct levels in human and experimental samples, and they are important in hepatocellular carcinoma research.

Algorithms↗
PubMed1996

v-erbA oncogene induces invasiveness and anchorage-independent growth in cultured glial cells by mechanisms involving platelet-derived growth factor.

The v-erbA oncogene coding for a mutated form of the thyroid hormone (T3) receptor (TR alpha 1) increased the invasion capacity of the mouse B3.1 glial cell line. This effect was mediated by the induction of platelet-derived growth factor (c-sis/PDGF B), as shown by its inhibition using an anti-PDGF BB antibody. Also, the low invasion capacity of parental B3.1 and c-erbA-expressing cells (B3.1 + TR alpha 1) was enhanced by exogenously added PDGF BB. This effect was independent of the growth-promoting activity of PDGF and unrelated to the secretion of metalloproteinases. All three cell types (parental B3.1, B3.1 + v-erbA, and B3.1 + TR alpha 1) secreted similar high levels of the M(r) 72,000 collagenase IV (A) independently of PDGF. Anchorage-independent cell growth was also enhanced by v-erbA; B3.1 + v-erbA cells but neither parental B3.1 nor B3.1 + TR alpha 1 cells formed foci in soft agar. The effect of v-erbA only happened in the presence of serum, suggesting that some serum factor(s) cooperate with PDGF to overcome the anchorage dependence of B3.1 + v-erbA cells. Supporting this, high doses of exogenous PDGF were much less efficient than serum, and the addition of an anti-PDGF BB antibody blocked only partially the effect of serum. Basic fibroblast growth factor was found to cooperate with PDGF to abolish anchorage dependence. Moreover, B3.1 + v-erbA cells detached and grew in suspension when cultured on plastic dishes. Interestingly, the transformation-competent c-jun and fra-1 oncogenes were induced by v-erbA in serum-free medium and are candidates to mediate v-erbA effects. In summary, our results show that v-erbA induces transformation parameters in the glial B3.1 cell line via an increase in c-sis/PDGF B and probably other mechanisms, suggesting a role for (autocrine) PDGF stimulation in glial cell transformation.

Animals↗
PubMed1996

[Allogenic bone marrow transplantation versus autograft in acute lymphoblastic leukemia, in second remission in 113 children. Results of the Grupo Español de Transplante de Medula Niños (GETMON)].

PURPOSE: Using the data from the GETMON ("Grupo Español de Trasplante de Medula Osea en Niños") we carried out a retrospective analysis of the results of allogeneic bone marrow transplantation (alloBMT) compared to autologous bone marrow transplantation (ABMT) in 113 paediatric patients with acute lymphoblastic leukaemia (ALL) in second remission. Transplants were performed by the following centers, from April 1983 to December 1991: H. Vall d'Hebrón and H. Sant Pau from Barcelona, H. Ramón y Cajal and H. Niño Jesús from Madrid and H. Marqués de Valdecilla from Santander. PATIENTS AND METHODS: The study included 113 patients between the ages of two and 16 years with ALL in second remission at marrow transplant. Fifty-six underwent alloBMT and 57 ABMT. Both groups were homogeneous with respect to age, sex, immunophenotype, duration of first remission, risk at diagnosis, percentage of early and late relapses, percentage with marrow or extramedullary relapse prior to transplant, time interval from attainment of second remission to transplant, and conditioning regimens applied for marrow transplant, with predominance of chemoradiotherapy in both. RESULTS: Haematologic recovery was observed to be faster in alloBMT than in ABMT. A granulocyte count > 0.5 x 10(9)/l was reached in alloBMT patients in a median of 19 days and in ABMT patients in a median of 25 days (p < 0.001). Early procedure-related death after ABMT occurred only in one patient (1.75%) and was caused by hepatic veno-occlusive disease. In the alloBMT group, the incidence was 25%. GVHD and infection were the most common causes. Actuarial DFS for alloBMT was 38.8 +/- 6.7% at 8.5 years versus 29.2 +/- 6.5% at 4.5 years for ABMT, p = NS. No significant differences of actuarial DFS were found between alloBMT or ABMT in patients according to leukocyte count and risk at diagnosis, neither with first remission duration, nor with remission duration at transplant. A separate analysis of actuarial DFS for each group shows that in ABMT group DFS was significantly greater in patients who had presented a late relapse (> 30 months) 61.1 +/- 13.8%, than those who had presented an early relapse (< 30 months) 18.3 +/- 6.5% (p < 0.005). Probability of relapse was significantly greater in ABMT (70%) compared to alloBMT (46%) (p < 0.025). Transplant offers a better DFS in extramedullary relapses compared to isolated or combined bone marrow relapses: 71.4 +/- 17.1% with alloBMT and 38.1 +/- 14.7% with ABMT (p = NS). CONCLUSIONS: In our experience we observed a better DFS with alloBMT compared with ABMT, overcoat in early relapses, but without significant difference. A higher relapse rate in ABMT group is partially compensated by more early deaths in alloBMT offers a few survival possibilities in patients with medullary relapses whose first remission lasted less than 30 months.

Adolescent↗
PubMed1996

Seroepidemiology of measles, mumps and rubella virus infections in normal children and adults in southern Granada, Spain: response to a vaccination programme.

A seroepidemiological study of measles, mumps and rubella virus infection in normal children and adults in southern Granada, Spain, and the response to a vaccination programme was carried out. Protection from the mumps and rubella virus was reduced in the group of 3 to 7 year-old children vaccinated at age 15 months indicating the need for revaccination against rubella as well as the mumps virus.

Adult↗
PubMed1996

[Renovascular hypertension. Radionuclide renography for detection and prediction of clinical response to revascularization].

The most frequently used non invasive tests in the diagnosis of renovascular hypertension are the measurement of peripheral blood renin before and after captopril administration, intravenous pyelogram, renal Doppler examination and radionuclide renography without and with angiotensin converting enzyme inhibitor administration. Measurement of renal vein renin levels and renal angiography are invasive tests commonly used. The latter allows an anatomical diagnosis of renal vein stenosis but does not give information about the functional consequences of such lesion and thus, does not predict the response of blood pressure to revascularization. Radionuclide renography has become the most useful non invasive diagnostic test, with a sensitivity and specificity of 83-94 and 85-97% respectively. It also predicts clinical response to revascularization and is useful for follow up after surgery or angioplasty. It also has good results in patients with renal failure, bilateral stenosis or stenosis in a solitary kidney and in transplanted patients.

Adult↗
PubMed1996

Neoadjuvant chemotherapy with continuous infusion of cisplatin and 5-fluorouracil, with or without leucovorin, for locally advanced nasopharyngeal carcinoma.

Cisplatin-based induction chemotherapy has been extensively tested in nasopharyngeal carcinoma for the improvement of local and systemic control and survival of this disease. In this study, we report the results of the treatment with induction chemotherapy in 40 patients with locally advanced carcinoma of the nasopharynx (LANPC) with four courses of cisplatin (P) 25 mg/m2 per day and 5-fluorouracil (F) 1000 mg/m2 per day both in a 4-days continuous infusion, with or without leucovorin (L) 250 mg/m2 per day in 2-hour infusion at the beginning of daily administration of PF, followed by sequential radiotherapy. All except one were in stage IV. The overall response after induction chemotherapy was 93%, with 55% CR and 38% PR. Definitive overall response after radiotherapy was 98%, with 80% CR and 18% PR. At a maximum follow up of 11 years, the overall survival rate is 55%. Induction chemotherapy with continuous infusion of PF with or without leucovorin followed by radiotherapy is a highly active regimen for the treatment of locally advanced nasopharyngeal carcinoma with response and survival rates comparable to other combinations of sequential or simultaneous chemotherapy and radiotherapy.

Adult↗
PubMed1996

[Bacterial urovirulence factors and their association with functional and anatomical abnormalities and recurrence of urinary tract infections in children].

BACKGROUND: Urinary tract infections in children are associated with functional and anatomical abnormalities of the urinary tract, they tend to recur and can cause permanent kidney damage. AIM: To study in children with urinary tract infections, microbiological factors associated to recurrence, functional and anatomical abnormalities of the urinary tract. PATIENTS AND METHODS: A prospective sample of children was incorporated into a follow-up protocol after their first episode of bacteriologically-demonstrated urinary tract infection. In all patients an abdominal ultrasound examination and a mictional urethrocystography were done and the presence of fimbriae was studied in isolated strains of Escherichia coli. RESULTS: Two hundred fifteen cases bad an adequate adherence to the study protocol, 190 caused by E coli. Fimbriated E coli strains were isolated with greater frequency from children with pyelonephritis than from those with a low urinary tract infection (50 and 28% respectively). The absence of fimbriae in E coli strains was associated with a higher risk of recurrent infections (odds ratio = 3, confidence intervals = 2-9.2) and an abnormal urethrocystography (odds ratio = 3, confidence intervals = 1.1-10.2). CONCLUSIONS: These data are consistent with foreign reports and support the need to study adhesins in E coli strains isolated from children with urinary tract infections.

Bacterial Infections↗
PubMed1996

[The need for nuclear medicine specialists and gamma cameras].

BACKGROUND: The ideal number of nuclear medicine specialists in relation to the needs of a given population should be defined by the institutions training such specialists. AIM: To establish the relationship between the number of gammacameras, nuclear medicine specialists and the number of inhabitants in different countries, including Chile. MATERIAL AND METHODS: Information was obtained from the International Atomic Energy Agency, Britannic and Canadian Nuclear Medicine Societies, Pan-American Health Organization and American College of Nuclear Physicians. RESULTS: Industrialized countries have approximately 1 specialist and 0.5-3.3 gammacameras per 100,000 inhabitants. The respective figures in Chile are 0.25 and 0.25. Due to the unequal distribution of resources in Chile, the specialist and gammacameras rate in the Metropolitan area is 0.6, some regions or communities do not have these resources and in other communities the rate can raise up to nine. CONCLUSIONS: Compared to industrialized countries, Chile lacks nuclear medicine specialists and gammacameras, and these resources are unevenly distributed.

Chile↗
PubMed1995

Anuran dorsal column nucleus: organization, immunohistochemical characterization, and fiber connections in Rana perezi and Xenopus laevis.

As part of a research program on the evolution of somatosensory systems in vertebrates, the dorsal column nucleus (DCN) was studied with (immuno)histochemical and tract-tracing techniques in anurans (the large green frog, Rana perezi, and the clawed toad, Xenopus laevis). The anuran DCN contains some nicotinamide adenine dinucleotide phosphate diaphorase-positive neurons, very little calbindin D-28k, and a distinct parvalbumin-positive cell population. The anuran DCN is innervated by primary and non-primary spinal afferents, by primary afferents from cranial nerves V, VII, IX, and X, by serotonin-immunoreactive fibers, and by peptidergic fibers. Non-primary DCN afferents from the spinal cord appear to arise throughout the spinal cord, but particularly from the ipsilateral dorsal gray. The present study focused on the efferent connections of the DCN, in particular the targets of the medial lemniscus. The medial lemniscus could be traced throughout the brainstem and into the diencephalon. Along its course, the medial lemniscus gives off collaterals to various parts of the reticular formation, to the octavolateral area, and to the granular layer of the cerebellum. At mesencephalic levels, the medial lemniscus innervates the lateral part of the torus semicircularis as well as various tegmental nuclei. A striking difference between the two species studied is that while in R. perezi medial lemniscal fibers do not reach the tectum mesencephali, in X. laevis, intermediate and deep tectal layers are innervated. Beyond the midbrain, both dorsal and ventral thalamic areas are innervated by the medial lemniscus. The present study shows that the anuran "lemniscal pathway" is basically similar to that of amniotes.

Animals↗
PubMed1995

HIV infection among female partners of seropositive men in Brazil. Rio de Janeiro Heterosexual Study Group.

A heterosexual partner study was carried out in Rio de Janeiro, Brazil, from August 1990 to December 1991. The main objectives were to determine the rate of male-to-female transmission of human immunodeficiency virus (HIV) and to determine risk factors. Male index cases were recruited according to the following criteria: 1) confirmed HIV positivity, 2) 18 years old or older; 3) heterosexual contact within the past year. Only female partners who reported not to have other risk factors but to have had sexual contact with the index case were invited to participate. Couples were interviewed for risk factors and had blood collected for laboratory studies. The overall prevalence of HIV infection was 45 percent among 204 female partners in the study. Using logistic regression, the authors found the following factors to be independently (p < 0.05) associated with HIV infection: 1) anal sex (odds ratio (OR) = 3.74, 95% confidence interval (CI) 1.87-7.45); 2) condom use during vaginal sex sometimes (OR = 1.45, 95% CI 1.07-1.96), rarely (OR = 2.10, 95% CI 1.15-3.83), or never (OR = 3.04, 95% CI 1.23-7.50) as compared with always; 3) frequency of sexual contacts in the year prior to interview (100+) (OR = 2.00, 95% CI 1.03-3.91); and 4) oral contraceptive use (OR = 2.04, 95% CI 0.97-4.29). In addition to a borderline significance of oral contraceptive use, there was a strong suggestion of an interaction with history of sexually transmitted diseases.

Adult↗
PubMed1995

Temporal trends of incident human immunodeficiency virus infection in a cohort of injecting drug users in Baltimore, Md.

OBJECTIVE: To measure the temporal trends in the incidence of infection with human immunodeficiency virus in a cohort of injecting drug users in Baltimore, Md, between 1988 and 1992. DESIGN: Study subjects were screened for antibodies to human immunodeficiency virus by enzyme-linked immunosorbent assay and confirmed with Western blot. They were followed up at 6-month intervals with repeated serologic screening and comprehensive interviews for human immunodeficiency virus risk factors. SETTING: Special study clinic. PARTICIPANTS: A cohort of 2960 participants were recruited and screened between February 1988 and March 1989. Recruitment criteria included an age of 18 years or older, a history of illicit drug injection since 1978, and the absence of the acquired immunodeficiency syndrome; subjects were subsequently tested for human immunodeficiency virus antibodies. Most subjects (85%) were not receiving methadone treatment at baseline and were recruited by word of mouth. MAIN OUTCOME MEASURE: Human immunodeficiency virus seroconversion. RESULTS: Of the 2247 seronegative participants at baseline, 1532 were followed up, and 188 (12.3%) had seroconverted by December 1992. The incidence of human immunodeficiency virus infection over time among users declined somewhat, especially among women; the overall incidence was 1.90 per 100 person-semesters, or 3.80% annually. The incidence, adjusted for gender, was higher in younger (< 35 years) than older (> or = 35 years) subjects (relative incidence, 1.75; 95% confidence interval, 1.29 to 2.38) and in women compared with men, adjusted for age (relative incidence, 1.29; 95% confidence interval, 0.95 to 1.80). The relative incidence among active compared with inactive drug users adjusted for age and gender was 1.58 (95% confidence interval, 1.06 to 2.35). CONCLUSIONS: Although the incidence of human immunodeficiency virus infection in this cohort of injecting drug users in Baltimore declined somewhat during the 4 years of follow-up, especially among women, the persistent annual incidence of nearly 4% during 3 1/2 to 4 1/2 years of observation suggests the need for additional strategies for prevention of infection, especially among those who continue injecting drugs. Newer methods of prevention, such as provision of sterile injection equipment, an effective human immunodeficiency virus vaccine, and wider availability of effective treatment or prevention of drug addiction, are urgently needed in these high-risk populations.

Adult↗
PubMed1995

Identification of the mitochondrial NADH dehydrogenase subunit 3 (ND3) as a thyroid hormone regulated gene by whole genome PCR analysis.

We previously described a modification of the whole genome PCR method which allowed us to characterize several genes whose expression is regulated by thyroid hormone in the mouse liver. Following this procedure, we now report the identification of the mitochondrial NADH dehydrogenase subunit 3 (ND3) gene as target of thyroid hormone. ND3 gene expression is regulated by thyroid hormone in rat brain and heart. Sequencing and electrophoretic mobility shift assays confirmed the presence of a thyroid hormone receptor (TR)/c-erbA specific binding site in the mitochondrial ND3 gene. Hypothyroidism decreases ND3 mRNA levels in several brain areas such as cortex and hippocampus during the early postnatal development. In line with the recent findings showing the presence of TR/c-erbA alpha and beta proteins inside the mitochondria, our results suggest the possibility of direct transcriptional regulation of mitochondrial genes by thyroid hormone.

Aging↗
PubMed1995

Long-term survivors with HIV-1 infection: incubation period and longitudinal patterns of CD4+ lymphocytes.

To characterize long-term survival with HIV-1, we need to estimate the proportion of seroconverters remaining free from clinical AIDS for long periods. We predict that approximately 13% of homosexual/bisexual men infected at a young age may remain so for > 20 years. Since studies have not followed individuals for such periods, long-term survivors must be characterized using stability of immunologic markers. In a cohort of 1,809 seropositive men followed since 1984-85, 15% (187/1,214) of those with at least two consecutive visits early in the study showed no decline in CD4+ cell count. From these, 67 men with long follow-up and no use of zidovudine were identified as cases to investigate correlates of protection against HIV-1-induced immunodepletion. Two matched control subgroups, one with moderate and one with rapid CD4+ lymphocyte decline, produced 56 triplets of individuals to be contrasted. Analysis of data from early in the study on demographics, sexual behavior, and sexually transmitted diseases revealed no significant differences among the three groups. Men showing no decline in CD4+ lymphocytes persistently showed a healthier profile with respect to onset of clinical AIDS, survival, and concomitant hematologic variables. Moderate decliners had rates of clinical AIDS and death significantly higher than those in the stable group but lower than the fast decliners.

CD4 Lymphocyte Count↗
PubMed1995

Induction of platelet-derived growth factor B/c-sis by the v-erbA oncogene in glial cells.

The v-erbA oncogene codes for a mutated form of the thyroid hormone receptor TR/c-erbA-alpha. Thyroid hormone (triiodothyronine, T3) regulates glial functions such as myelination and both astrocytes and oligodendrocytes have been shown to express thyroid hormone receptors (TRs). To study putative effects of v-erbA on glial precursors, we have expressed it in a glial clonal cell line established from early embryonal mouse brain. We have found that v-erbA increases cell survival in serum-free conditions. Moreover, v-erbA-expressing cells show a substantial growth in the presence of insulin or IGF-I, whereas normal and TR/c-erbA-over-expressing cells progressively degenerate. By Northern blotting, immunofluorescence, immunoprecipitation, and neutralization experiments, we show that v-erbA actions are mediated by an increase in the levels of PDGF B/c-sis mRNA and protein. We used anti-PDGF receptor and anti-phosphotyrosine antibodies to show the constitutive activation of PDGF receptors in B3.1 + v-erbA cells, and neutralizing anti-PDGF antibodies to demonstrate that v-erbA enhances the secretion of active PDGF into the culture medium. Our data indicate that v-erbA induces PDGF B/c-sis, a factor involved in the generation of gliomas, the most common central nervous system tumor in humans.

3T3 Cells↗
PubMed1995

Thyroid hormone regulates stromelysin expression, protease secretion and the morphogenetic potential of normal polarized mammary epithelial cells.

Stromelysins are a group of proteases which degrade the extracellular matrix and activate other secreted proteases. Stromelysin (ST)-1 and ST-2 genes are induced by tumor promoters, oncogenes and growth factors, and have been involved in acquisition of the malignant phenotype. We show here that the thyroid hormone (T3) increases ST-1 and ST-2 expression in a non-transformed mouse mammary epithelial cell line (EpH4) in a way that is dependent on the level of thyroid receptor/c-erbA (TR alpha-1) expression. In agreement with this, T3 increases the secreted stromelysin activity and enhances the gelatinolytic activity of type IV collagenase. We have also demonstrated that T3 affects the epithelial polarity of EpH4 cells, diminishing the transepithelial electrical resistance of monolayers cultured on permeable filters, causing an abnormal distribution of polarization markers and the disruption of the organized 3-D structures formed by these cells in type I collagen gels. These results indicate that the ligand-activated TR alpha-1 plays an important role in regulating the morphogenetic and invasive capacities of mammary epithelial cells. Because the c-erbA locus is altered in several types of carcinoma, an altered or deregulated TR alpha-1 expression may also be important for breast cancer development and metastasis.

Animals↗