Biomedical subjects

T Garcia

Publications and source records attributed to T Garcia.

At least 19 recordsLinked to original sources

PubMed2005

Effect of parathyroidectomy on renal graft function.

Some authors have reported acute impairment of renal transplant function after parathyroidectomy (PTx). Since 1996 PTx has been performed in 22 renal transplant recipients (follow-up, 24.2 +/- 15 months; serum creatinine concentration (SCr) pre-PTx, 1.26 +/- 0.4 mg/dL). We analyzed the serum levels of immunoreactive parathyroid hormone, calcitriol, calcium, phosphate, alkaline phosphatase, SCr, and hemoglobin, as well as proteinuria, blood pressure, and immunosuppressive treatment at several times: before PTx and at 7 days, 1 month, and then every 3 months post-PTx. After PTx we observed acute renal function deterioration until the third post-PTx month, when SCr levels returned to baseline values. We found no changes in blood pressure, although there was a trend toward a reduced dosage of antihypertensive drugs. We compared the patients who showed more significant increases (>30% from baseline) in SCr (group A, n = 7) with those who did not (group B, n = 15). Group A had higher SCr levels pre-PTx. We observed no other significant differences, either pre-PTx or post-PTx. In 2 patients in group A, SCr returned to baseline at the third month after PTx, but in the other 5 the renal function impairment persisted. Taking into account this risk and that severe hyperparathyroidism does not revert after transplantation, it would seem more appropriate in such cases to perform PTx while the patient is on the waiting list. The causes of this renal functional impairment are not clear, but the patients who showed worse deterioration also had a worse renal function pre-PTx.

Antihypertensive Agents↗

PubMed2005

Treatment with adefovir dipivoxil in a renal transplant patient with renal insufficiency and lamivudine-resistant hepatitis B infection.

Lamivudine is a safe, effective treatment for hepatitis B virus (HBV) reactivation after renal transplantation. However, prolonged lamivudine therapy can produce resistance to the drug. Adefovir dipivoxil (ADV) has demonstrated efficacy in patients with lamivudine resistance, but there is limited clinical experience in patients with either renal transplants or severe renal insufficiency. A 47-year-old man with asymptomatic HBV infection underwent renal transplantation in November 1995. In September 2000 lamivudine therapy was initiated to treat HBV reactivation. The outcome was good, with negative HBV DNA levels. Two years later, significant viral replication developed again. At that time the patient already had advanced renal insufficiency due to chronic graft nephropathy. The transaminase levels were increased, and the HBV DNA reached greater than 200,000 copies/mL by polymerase chain reaction, with development of ascites and cirrhosis. The patient was started on ADV 10 mg every 72 hours (dose adjusted to renal function). There was rapid normalization of hepatic enzymes and progressive decline of the viral load. HBV DNA became negative after 6 months of ADV treatment. The renal function has since remained stable. This case suggests that ADV can be safe and effective in the treatment of renal transplant patients with lamivudine-resistant hepatitis B, even in the presence of advanced renal insufficiency.

Adenine↗

PubMed2004

A non-invasive method for measurement of gastric emptying in mice: effects of altering fat content and CCK A receptor blockade.

The ability to make repetitive non-invasive measurements of gastric emptying of nutritive solids in awake, unstressed mice is highly desirable. The aim of the present study was to develop such a technique using nuclear scintigraphy and diets differing in triglyceride content. Awake mice were accustomed to light restraint and to feeding cooked, egg white (0.00 g fat g(-1)), whole egg (0.10 g fat g(-1)), or egg yolk (0.31 g fat g(-1)). Gastric emptying of each diet was measured by labelling the test meals with Technetium(99m) Mebrofenin and using a conventional gamma camera equipped with a high resolution, parallel hole collimator. Gastric emptying of cooked whole egg was also determined following administration of either vehicle or CCK A receptor antagonist, devazepide. The half-emptying time (t(1/2)) significantly increased with increasing triglyceride content from 14 +/- 5 min to 51 +/- 6 min and 82 +/- 4 min for egg white, whole egg and egg yolk, respectively. Administration of devazepide significantly decreased t(1/2) of whole egg to 28 +/- 2 min. These results demonstrate the sensitivity and predictability of this technique in mice and importantly, provide an opportunity to alter the macronutrient or caloric content of the meal to determine effects on gastric emptying.

Animals↗

PubMed2003

Identification of genes regulated during osteoblastic differentiation by genome-wide expression analysis of mouse calvaria primary osteoblasts in vitro.

Although several independent studies of gene expression patterns during osteoblast differentiation in cultures from calvaria and other in vitro models have been reported, only a small portion of the mRNAs expressed in osteoblasts have been characterized. We have previously analyzed the behavior of several known markers in osteoblasts, using Affymetrix GeneChip murine probe arrays (27,000 genes). In the present study we report larger groups of transcripts displaying significant expression modulation during the culture of osteoblasts isolated from mice calvaria. The expression profiles of 601 such regulated genes, classified in distinct functional families, are presented and analyzed here. Although some of these genes have previously been shown to play important roles in bone biology, the large majority of them have never been demonstrated to be regulated during osteoblast differentiation. Despite the fact that the precise involvement of these genes in osteoblast differentiation and function needs to be evaluated, the data presented herein will aid in the identification of genes that play a significant role in osteoblasts. This will provide a better understanding of the regulation of osteoblast differentiation and maturation.

Animals↗

PubMed2002

Behavior of osteoblast, adipocyte, and myoblast markers in genome-wide expression analysis of mouse calvaria primary osteoblasts in vitro.

Several genes, such as alkaline phosphatase, osteocalcin, and Cbfa1/Osf2, are known to be regulated during osteoblastic differentiation and are commonly used as "osteoblast markers" for in vitro or in vivo studies. The number of these genes is very limited, however, and it is of major interest to identify new genes that are activated or repressed during the process of osteoblast differentiation and bone formation as well as to extend the available information on gene families relevant to this particular differentiation pathway. To identify such genes, we have implemented a genome-wide analysis by determining changes in expression levels of 27,000 genes during in vitro differentiation of primary osteoblasts isolated from mouse calvaria. This study focuses on the description of the analytical and filtering process applied; on the transcriptional analysis of well-established "bone," "adipocyte," and "muscle" pathway markers; and on a description of the regulation profiles for genes recently described in the Skeletal Gene Database. We also demonstrate that new array technologies constitute reliable and powerful tools to monitor the transcription of genes involved in osteoblastic differentiation, allowing a more integrated vision of the biological pathways regulated during osteoblast commitment, differentiation, and function.

Adipocytes↗

PubMed2001

LDL receptor-related protein 5 (LRP5) affects bone accrual and eye development.

In humans, low peak bone mass is a significant risk factor for osteoporosis. We report that LRP5, encoding the low-density lipoprotein receptor-related protein 5, affects bone mass accrual during growth. Mutations in LRP5 cause the autosomal recessive disorder osteoporosis-pseudoglioma syndrome (OPPG). We find that OPPG carriers have reduced bone mass when compared to age- and gender-matched controls. We demonstrate LRP5 expression by osteoblasts in situ and show that LRP5 can transduce Wnt signaling in vitro via the canonical pathway. We further show that a mutant-secreted form of LRP5 can reduce bone thickness in mouse calvarial explant cultures. These data indicate that Wnt-mediated signaling via LRP5 affects bone accrual during growth and is important for the establishment of peak bone mass.

Adaptor Proteins, Signal Transducing↗

PubMed2000

Changes in iron status during pregnancy in peruvian women receiving prenatal iron and folic acid supplements with or without zinc.

BACKGROUND: Iron deficiency anemia is the most prevalent nutrient deficiency during pregnancy, yet there are few data on the effect of prenatal iron supplementation in women in developing countries. OBJECTIVE: Our objective was to describe the effect of iron supplementation on hematologic changes during pregnancy, and the effect on those changes of adding zinc to the supplements. DESIGN: Pregnant women were enrolled in a randomized, double-masked study conducted at a hospital in a shantytown in Lima, Peru. Women were supplemented daily from 10-24 wk gestation to 4 wk postpartum with 60 mg Fe and 250 microg folic acid with or without 15 mg Zn. Hemoglobin and ferritin concentrations were measured in 645 and 613 women, respectively, at enrollment, at 28-30 and 37-38 wk gestation, and in the cord blood of 545 neonates. RESULTS: No differences in iron status were detected by supplement type, but hematologic changes were related to initial hemoglobin status. Women with anemia (hemoglobin <110 g/L) showed steady increases in hemoglobin concentration throughout pregnancy whereas women with relatively higher initial hemoglobin concentrations had declining values during mid pregnancy, then rising values by 37-38 wk gestation. Women with an initial hemoglobin concentration >95 g/L showed increases in serum ferritin by the end of the pregnancy. Despite supplementation, women with poorer hematologic status; who were younger, single, and multiparous; and who consumed fewer supplements were more likely to have anemia at the end of pregnancy. CONCLUSIONS: These hematologic changes are congruent with the effects of iron supplementation reported in placebo-controlled trials and the addition of zinc did not significantly affect them.

Adolescent↗

PubMed2000

Efficacy and acceptability of two iron supplementation schedules in adolescent school girls in Lima, Peru.

To assess the efficacy and acceptability of a daily and intermittent iron supplementation, a double-blind, placebo-controlled trial was conducted in a public school located in periurban Lima, Peru. Adolescent girls (n = 312), 12-18 y old, were randomly assigned to one of the following three groups: 1) 60 mg iron as ferrous sulfate daily from Monday to Friday; 2) 60 mg iron as ferrous sulfate 2 d/wk and 3 d placebo (intermittent); 3) placebo, from Monday to Friday. Field workers gave the girls supplements during school hours for 17 wk; 296 girls completed the trial. Girls took 94% of the expected dose of 85 pills. Few side effects were reported. Postintervention, hemoglobin (Hb), serum ferritin (SF) and free erythrocyte protoporphyrin (FEP) were improved significantly in the iron-supplemented groups compared with placebo (P<0.05). Daily supplements led to higher Hb increases than intermittent supplements (P<0.05), but SF and FEP were similar between the two groups. Thus, both iron supplementation schedules were efficacious in preventing iron deficiency in adolescent girls through the school system, and the daily schedule was better than the intermittent schedule at increasing Hb values and reducing anemia.

Adolescent↗

PubMed1999

Cardiac troponin T as a marker for myocardial ischemia in patients seen at the emergency department for acute chest pain.

BACKGROUND: Identification of patients with acute chest pain at high risk for cardiovascular complications is a common and difficult challenge for clinicians and must be based initially on data from the history, physical examination, electrocardiogram, and chest radiograph. Some data suggest that elevations in cardiac troponin T (cTnT) may be useful for detection of less severe degrees of myocardial injury that may occur in some patients with unstable angina. Therefore we designed a prospective follow-up study to assess the diagnostic performance and prognostic value of cTnT in a population of patients presenting to the emergency department with acute chest pain. METHODS: The patient population included all 1477 admitted patients aged 30 years or more who presented to the emergency department of an urban teaching hospital from October 1992, through February 1994, with a chief symptom of acute chest pain not explained by trauma or chest radiograph abnormalities. The 1303 patients (88%) who had 2 or more measurements of cTnT during the first 24 hours after presentation comprised the final study population. Sensitivity, specificity, positive predictive value, negative predictive value, and receiver operator characteristics curve (ROC) were determined for cTnT and creatine kinase-MB (CK-MB) (measured using activity and mass assays) data from the first 24 hours after admission for the outcomes of acute myocardial infarction (AMI) and major cardiac events during the first 72 hours of hospitalization. RESULTS: The sensitivity and specificity of cTnT (threshold of 0.1 ng/mL) for detecting AMI during the first 24 hours after presentation were 99% and 86%, respectively. The CK-MB activity and mass assays had diagnostic performance for detecting AMI similar to cTnT. Among patients who did not meet study criteria for AMI, cTnT was elevated during the first 24 hours in 31% of patients who had major complications, compared with a 17% rate for the CK-MB activity assay and a 3% rate for the CK-MB mass assay. In these patients, the cTnT assay had superior diagnostic performance compared with the CK-MB mass assay as a marker for cardiac complications as assessed with ROC analysis (P <.0004). CONCLUSIONS: In a heterogeneous population of patients seen in the emergency department with acute chest pain, cTnT was similar to CK-MB (activity and mass assays) for detection of AMI and superior to the CK-MB mass assay as a marker for major cardiac events early in the hospital course among those who were ruled out for an AMI. Further study is required to determine how this assay can be used to provide more appropriate, cost-effective care.

Acute Disease↗

PubMed1998

Solving the complementarity dilemma: evolving strategies for simultaneous hermaphroditism.

We introduce a complementarity dilemma, a two-player, binary response game in which the playoffs are highest when the two players respond differently. Using the classifier EvA, we determine the evolutionary dynamics and structure of strategies that evolve to play an iterated version of this game, and we relate the results to the evolution of major types of sexual reproduction, particularly simultaneous hermaphroditism. We find that complementarity strategies consistently evolve under a broad range of conditions, but that those most consistent with the simultaneous hermaphroditism can predominate only when a substantial cost of repeatedly adopting the female role is imposed. The cost is analogous to the fecundity reduction to be expected when a single partner must repeatedly produce the eggs in sexual reproduction.

Animals↗

PubMed1998

Modeling the Mediating Role of Volition in the Learning Process.

According to action-control theory, volition plays a mediating role between the intention to learn (motivation) and goal-directed behavior (the use of learning strategies). Although extensive theoretical work has been done to document this flow of events, more empirical studies have been needed to identify the specific means by which volitional control protects the intention to learn and maintains the attempts to learn; our intention here was to address this gap in the literature. Using data from a sample of 487 college students in two different domains, we found that the positive effects of intrinsic goal orientation and self-efficacy on cognitive engagement were augmented by volitional control. We also found that the effects of volition differed by domain as well as by the type of learning strategy being considered. These results suggest that volitional control merits greater attention from those doing research in self-regulated learning. Copyright 1998 Academic Press.

Journal Article↗

PubMed1997

Estrogen receptor impairs interleukin-6 expression by preventing protein binding on the NF-kappaB site.

Interleukin-6 (IL-6) is a multifunctional cytokine thought to be a key factor in post-menopausal osteoporosis, given its ability to induce osteoclast maturation and its down regulation by estrogens. We have previously shown that the effects of TNFalphaand estradiol on the human IL-6 promoter were dependent on a region of the promoter containing a C/EBP site and a NF-kappaB site. To define the molecular mode of action of estrogens, we performed gel shift assays with this DNA fragment as a probe, and nuclear extracts from TNFalpha-induced HeLa, MCF7 and Saos2 cells. Several induced complexes specifically bound the probe. The use of various competitor DNA suggested that most of the complexes detected contained NF-kappaB factors, and that C/EBP site binding factors were important for the overall binding to the probe. Addition of in vitro translated human estrogen receptor (hER) impaired the binding of three complexes in HeLa cells and two complexes in MCF7 and Saos2 cells. Competition experiments suggested that the NF-kappaB site was necessary for the effect of hER. The use of antisera against NF-kappaB and C/EBP proteins showed that the target complexes of hER contained the c-rel proto-oncogene product and to a lesser extent, the RelA protein. Taken together, these data show that hER impairs TNFalphainduction of IL-6 by preventing c-rel and, to a lesser extent, RelA proteins binding to the NF-kappaB site of the IL-6 promoter.

Binding Sites↗

PubMed1997

A common binding site mediates heterodimerization and homodimerization of Bcl-2 family members.

Bcl-2 inhibits apoptosis induced by a wide variety of stimuli. In contrast, the Bcl-2 homologue, Bax, antagonizes Bcl-2's death protecting function. Bcl-2 forms protein-protein homodimers with itself and heterodimers with Bax, and previous experiments have shown that point mutations in Bcl-2 can abrogate Bax binding while leaving homodimerization intact. These mutagenesis results can be interpreted to suggest that Bcl-2 has separate binding sites that are responsible for homodimer and heterodimer formation. Results from yeast two-hybrid studies have also suggested that homodimerization and heterodimerization reflect distinct modes of interaction. However, using quantitative plate binding assays, we now show that Bax as well as peptides derived from the BH3 domains of Bax and Bak block both Bcl-2/Bax binding and Bcl-2/Bcl-2 binding. Similar assays demonstrate that Bcl-xL can form both homodimers and heterodimers and that these interactions are also inhibited by Bax and the BH3-derived peptides. These results demonstrate that the same binding motifs are responsible for both homodimerization and heterodimerization of Bcl-2 family members.

Amino Acid Sequence↗

PubMed1997

Significance of a false-positive trisomy 18 multiple-marker screening test.

OBJECTIVE: To determine if a false-positive trisomy 18 multiple-marker screening test (all three analytes low: maternal serum alpha-fetoprotein [AFP] at most 0.75 multiples of the median [MoM], unconjugated estriol at most 0.60 MoM, and hCG at most 0.55 MoM) indicates increased risk for obstetric complications or is related to maternal weight. METHODS: We accessed our genetic database to obtain multiple-marker screening test results, fetal karyotypes, and pregnancy outcomes from all patients with a normal multiple-marker screening test (n = 3900) and from all patients with a positive trisomy 18 screening test (n = 103) seen in the prenatal diagnosis clinic from 1992 to 1996. During this period, only maternal serum AFP was adjusted for maternal weight. RESULTS: A positive trisomy 18 screen identified five of 12 trisomy 18 fetuses. Women with a false-positive trisomy 18 screen were heavier (175.6 +/- 43.8 lb versus 159.9 +/- 37.9 lb, P < .001) and younger (29.7 +/- 6.5 years versus 32.3 +/- 6.5 years, P < .001) than women with a normal multiple-marker screening test, but were not at increased risk for pregnancy complications. Weight-adjusting all three analytes reduced the false-positive trisomy 18 screen rate by 42% (from 1.9% to 1.1%) but did not change the trisomy 18 detection rate. CONCLUSION: A false-positive trisomy 18 screening test does not indicate increased risk to develop pregnancy complications and may be related to inadequate correction for increased maternal weight.

Adult↗

PubMed1997

Growth of Vibrio anguillarum in Salmon Intestinal Mucus.

The physiological changes of Vibrio anguillarum in response to growth in salmon intestinal mucus were investigated. Growth, survival, and changes in protein expression during growth in media supplemented with mucus were compared to growth and starvation in the identical media without mucus. V. anguillarum exhibited a rapid decline in CFU following growth in mucus as the sole carbon source. No such decline was observed in Luria broth with a 2% NaCl concentration, in glucose-minimal broth (3M), or during starvation in a carbon-, nitrogen-, and phosphorus-free salt solution (NSS). The changes in protein expression during growth in mucus were examined by labeling cells with [(sup35)S]methionine and analyzing the labeled proteins by one- and two-dimensional gel electrophoresis and autoradiography. Comparison of [(sup35)S]methionine-labeled proteins from mucus-grown cells with 3M-grown cells and NSS-starved cells revealed four de novo mucus-inducible proteins (Mips). These Mips were localized in the membrane fraction of V. anguillarum. Additionally, at least one other membrane protein was found to have increased expression in response to growth in mucus.

Journal Article↗

PubMed1997

Synthetic glucocorticoids that dissociate transactivation and AP-1 transrepression exhibit antiinflammatory activity in vivo.

Some of the most potent antiinflammatory and immunosuppressive agents are synthetic glucocorticoids. However, major side effects severely limit their therapeutic use. The development of improved glucocorticoid-based drugs will require the separation of beneficial from deleterious effects. One possibility toward this goal is to try to dissociate two main activities of glucocorticoids, i.e. transactivation and transrepression. Screening of a library of compounds using transactivation and AP-1 transrepression models in transiently transfected cells identified dissociated glucocorticoids, which exert strong AP-1 inhibition but little or no transactivation. Importantly, despite high ligand binding affinity, the prototypic dissociated compound, RU24858, acted as a weak agonist and did not efficiently antagonize dexamethasone-induced transcription in transfected cells. Similar results were obtained in hepatic HTC cells for the transactivation of the endogenous tyrosine amino transferase gene (TAT), which encodes one of the enzymes involved in the glucocorticoid-dependent stimulation of neoglucogenesis. To investigate whether dissociated glucocorticoids retained the antiinflammatory and immunosuppressive potential of classic glucocorticoids, several in vitro and in vivo models were used. Indeed, secretion of the proinflammatory lymphokine interleukin-1beta was severely inhibited by dissociated glucocorticoids in human monocytic THP 1 cells. Moreover, in two in vivo models, these compounds exerted an antiinflammatory and immunosuppressive activity as potent as that of the classic glucocorticoid prednisolone. These results may lead to an improvement of antiinflammatory and immunosuppressive therapies and provide a novel concept for drug discovery.

Animals↗

PubMed1997

Sequences in the ligand-binding domains of the human androgen and progesterone receptors which determine their distinct ligand identities.

The natural ligands of the progesterone (PR) and androgen (AR) receptors, progesterone and testosterone, differ only by their 17 beta-substitution. To identify within the AR and PR ligand-binding domains (LBDs) the sequences responsible for the differential recognition of these ligands, chimeric LBDs assembled from five homologous AR/PR 'cassettes' linked to the GAL4-DNA binding domain were constructed, and their ligand binding and transactivation characteristics were determined. Replacing the central cassette 3 of PR by that of AR generated a progesterone- and testosterone-responsive PR LBD with the AR residues 788-RHLS-791 being specifically involved in testosterone recognition, while the introduction of the C-terminal PR cassette 5 into AR conferred progestin responsiveness onto the AR LBD. These results suggest that residues within AR 788-RHLS-791 interact with the testosterone 17 beta-OH, while PR cassette 5 apparently contains the amino acid(s) specifically involved in the recognition of the progesterone 17 beta-acetyl group. However, ligand binding and transactivation by these chimeras were significantly decreased compared with those of the parental LBDs, indicating that residues located outside of these cassettes contribute to the proper positioning of the steroids in the AR and PR ligand-binding pockets (LBPs). Indeed, certain AR/PR chimeras acquired efficient ligand binding, but were unable to transactivate, indicating that the ligand was improperly bound in the chimeric. LBP and could not induce the conformational changes leading to a transcriptionally competent activation function (AF-2) within the LBD. The properties of the various LBD chimeras are discussed in view of the recently solved three-dimensional structures of the retinoid X receptor alpha apo- and retinoic acid receptor gamma holo-LBDs.

Amino Acid Sequence↗

PubMed1996

The Effects of Autonomy on Motivation and Performance in the College Classroom

The goals of this study were to extend the literature about classroom autonomy in several ways. First, since previous research on autonomy has tended to focus on younger learners, we examined whether the positive effects of autonomy on motivation and performance would be replicated in a college sample. Second, we tested to see whether the well-established links between intrinsic motivation and autonomy would also be found using motivational constructs that play key roles in learning (specifically, task value, self-efficacy, and test anxiety). Third, we sought to trace the effect of autonomy on changes in student motivation over the course of a semester. Finally, we examined the role of autonomy on course performance. We found that experiences of classroom autonomy in the college classroom were more closely related to motivational factors than to performance. While the immediate experience of autonomy may not be directly facilitative of high course grades, autonomy does seem to foster intrinsic goal orientation, task value, and self-efficacy, all of which are critical components of "continuing motivation." The data presented here lend further support for the benefits of fostering autonomy within academic settings.

Journal Article↗