Biomedical subjects

R Garcia

Publications and source records attributed to R Garcia.

At least 73 records · Page 4Linked to original sources

PubMed2000

Cationic Re(V) oxo complexes with poly(pyrazolyl)borates: synthesis, characterization, and stability.

Cationic Re(V) oxo compounds of the type [ReO(OSiMe3)(eta 2-B(pz)4)(L)2]X [X = Cl, L = 4-(NMe2)C5H4N (1), 1-Meimz (1-methylimidazole; 2), 1/2 dmpe (1,2-bis(dimethylphosphino)ethane; 3), py (4a); X = I, L = py (4b)] can be prepared by reacting trans-[ReO2(eta 2-B(pz)4)(L)2] with XSiMe3. In solution, cations 1-4 are reactive species, and those with unidentate nitrogen donor ligands (1, 2, and 4) rearrange into the neutral derivatives [ReO(Cl)(OSiMe3)(eta 2-B(pz)4)(L)] [L = py (5), 4-(NMe2)C5H4N (6), 1-Meimz (7)], which are also reported herein. Compounds 1-3 and 5-7 have been fully characterized by the usual spectroscopic techniques, which in some cases includes X-ray crystallographic analysis (3, 6, and 7). Compound 3 crystallizes from CH2Cl2/n-hexane as yellow crystals with one molecule of CH2Cl2 solvent, and compounds 6 and 7 crystallize from THF/n-hexane as violet and red crystals, respectively, with one molecule of THF solvent in the case of 6. Crystallographic data: 3, orthorhombic space group Pn2(1)a, a = 11.311(2) A, b = 19.135(2) A, c = 15.443(2) A, V = 3342.4(8) A3, Z = 4; 6, triclinic space group P1, a = 8.7179(11) A, b = 12.5724(8) A, c = 17.750(2) A, alpha = 70.454(7) degrees, beta = 77.935(9) degrees, gamma = 77.129(8) degrees, V = 1768.1(3) A3, Z = 2; 7, monoclinic space group P2(1)/c, a = 16.356(2) A, b = 20.384(3) A, c = 17.360(3) A, beta = 106.971(12) degrees, V = 5535.8(14) A3, Z = 8.

Journal Article↗

PubMed2000

STATs in oncogenesis.

Since their discovery as key mediators of cytokine signaling, considerable progress has been made in defining the structure-function relationships of Signal Transducers and Activators of Transcription (STATs). In addition to their central roles in normal cell signaling, recent studies have demonstrated that diverse oncoproteins can activate specific STATs (particularly Stat3 and Stat5) and that constitutively-activated STAT signaling directly contributes to oncogenesis. Furthermore, extensive surveys of primary tumors and cell lines derived from tumors indicate that inappropriate activation of specific STATs occurs with surprisingly high frequency in a wide variety of human cancers. Together, these findings provide compelling evidence that aberrant STAT activation associated with oncogenesis is not merely adventitious but instead contributes to the process of malignant transformation. These studies are beginning to reveal the molecular mechanisms leading to STAT activation in the context of oncogenesis, and candidate genes regulated by STATs that may contribute to oncogenesis are being identified. Recent studies suggest that activated STAT signaling participates in oncogenesis by stimulating cell proliferation and preventing apoptosis. This review presents the evidence for critical roles of STATs in oncogenesis and discusses the potential for development of novel cancer therapies based on mechanistic understanding of STAT signaling. Oncogene (2000).

Animals↗

PubMed2000

Activation of Stat3 preassembled with platelet-derived growth factor beta receptors requires Src kinase activity.

Members of the STAT family of transcriptional regulators modulate the expression of a variety of gene products that promote cell proliferation, survival and transformation. Although initially identified as mediators of cytokine signaling, the STAT proteins are also activated by, and thus may contribute to the actions of, polypeptide growth factors. To define the mechanism by which these factors activate STATs, we examined the process of Stat3 activation in Balb/c-3T3 fibroblasts treated with platelet-derived growth factor (PDGF). As STATs are activated by tyrosine phosphorylation, and as PDGF receptors are ligand-activated tyrosine kinases, we considered the possibility that Stat3 interacts with and is phosphorylated by PDGF receptors. We find that Stat3 associates with PDGF beta receptors in both the presence and, surprisingly, the absence of PDGF. Moreover, Stat3 was phosphorylated on tyrosine in PDGF beta receptor immunoprecipitates of PDGF-treated but not untreated cells. Although required, receptor activation was insufficient for Stat3 activation. When added to cells in combination with a pharmacologic agent (PD180970) that specifically inhibits the activity of Src family tyrosine kinases, PDGF did not activate Stat3 as monitored by electrophoretic mobility shift assay. PD180970 did not affect MAPK activation by PDGF or the JAK-dependent activation of Stat3 by interleukin-6. The necessity of Src activity for Stat3 activation by PDGF was further evidenced by data showing the presence of Src in complexes containing both Stat3 and PDGF beta receptors in PDGF-treated cells. These results suggest a novel mechanism of STAT activation in which inactive Stat3 pre-assembles with inactive PDGF receptors, and in response to ligand binding and in a manner dependent on Src kinase activity, is rapidly phosphorylated and activated. Additional data demonstrate that Src kinase activity is also required for PDGF stimulation of DNA synthesis in density-arrested cells.

3T3 Cells↗

PubMed2000

Lipomatosis, proximal myopathy, and the mitochondrial 8344 mutation. A lipid storage myopathy?

Multiple symmetric lipomatosis (MSL) has been related in some cases to the 8344 point mutation of the tRNA-lysine gene of the mitochondrial DNA, mainly in the context of families with classic myoclonic epilepsy with ragged-red fibers (MERRF) and exceptionally in patients with proximal myopathy as the only manifestation of mitochondrial disease. We report on two families harboring the 8344 mutation. The patients presented with MSL and myopathy, expressed as limb girdle weakness in index cases and as exercise intolerance in the others. All muscle biopsies performed showed lipid storage apart from RRF and respiratory chain complexes deficiency. A possible explanation for both adipose proliferation and lipid storage myopathy in these cases is a disturbance in intermediary lipid metabolism secondary to mitochondrial respiratory chain deficiency that could be related via carnitine deficiency.

Adolescent↗

PubMed2000

Increased chitin synthesis in response to type II myosin deficiency in Saccharomyces cerevisiae.

We reported previously that the chitin content in cell walls of type II myosin-deficient Saccharomyces cerevisiae strains is increased relative to wild-type cells suggesting that increased chitin synthesis is induced in these strains. In the present study, we have performed enzyme activity assays for chitin synthases 1, 2, and 3 to determine the enzyme isoform(s) involved. To determine if transcriptional regulation is involved, we conducted quantitative mRNA assays of the corresponding chitin synthase genes. We show that the enzyme activities of all three chitin synthases increase substantially over the wild-type strain while eight- and twofold increases in the mRNA levels for chitin synthases 1 and 3 were detected. Increases in enzyme activities and mRNA levels were not proportional. We conclude that the enzyme activities for all three chitin synthases are elevated in this strain and that this increase is mediated mainly by a posttranslational mechanism(s). The heightened sensitivity to osmotic stress and the corresponding increase in cell wall chitin content reported in these strains are consistent with a compensatory "stress response" mechanism induced by abnormal cell wall assembly.

Cell Death↗

PubMed2000

A comparison of different postures for scaffold end-frame disassembly.

Overexertion and fall injuries comprise the largest category of nonfatal injuries among scaffold workers. This study was conducted to identify the most favourable scaffold end-frame disassembly techniques and evaluate the associated slip potential by measuring whole-body isometric strength capability and required coefficient of friction (RCOF) to reduce the incidence of injury. Forty-six male construction workers were used to study seven typical postures associated with scaffold end-frame disassembly. An analysis of variance (ANOVA) showed that the isometric forces (334.4-676.3 N) resulting from the seven postures were significantly different (p < 0.05). Three of the disassembly postures resulted in considerable biomechanical stress to workers. The symmetric front-lift method with hand locations at knuckle height would be the most favourable posture; at least 93% of the male construction worker population could handle the end frame with minimum overexertion risk. The static RCOF value resulting from this posture during the disassembly phase was less than 0.2, thus the likelihood of a slip should be low.

Accidental Falls↗

PubMed2000

The fifth evolutionary era in infection control: interventional epidemiology.

A historical review of infection control over the last 4 decades indicates that the field has evolved from being one whose investigative work laid the foundation for understanding the chain of infection to an influential profession whose research on effective prevention methods have revoluntionized clinical practice throughout the world. Underlying our successes is the fact that growth in the profession has brought with it an enormous expansion in responsibilities, which in turn has impacted, in some cases severely, the personnel and time resources of infection control departments. At the same time, the economic pressures brought on by the upheavals in the business of health care have trickled down wherein it now influences the makeup and effectiveness of infection control programs. To continue with our mission of reducing morbidity and mortality, and perhaps to avoid a diminishing of our own professional influence, it will become essential that new approaches to the management of infection control programs be implemented. The approach must start by incorporating a basic mandate for change in the infection control professional.

Cross Infection↗

PubMed2000

Evaluation of heavy metal availability in polluted soils by two sequential extraction procedures using factor analysis.

Superficial soil and grass samples from 13 locations affected by several anthropogenic sources (mining, metal factory, traffic emissions) were collected in Gipuzkoa, northern Spain. The more labile metal fractions, the mobile (extracted by 0.01 mol l(-1) CaCl(2)) and the mobilisable (extracted by 0.005 mol l(-1) DTPA), were evaluated using a short sequential procedure with two steps. From the results a short-medium term potential lability of Cd, Cu, Zn and Pb can be concluded. The labile levels were compared with the results obtained using the Tessier sequential procedure. Factor analysis was used to check the associations between the total metal contents in soil and grass, as well as between the levels of the different sequential fractions and the total content in grass. Cd, Cu and Zn labile levels were related to total metal grass contents indicating its suitability for the availability studies in polluted soil-plant system.

Journal Article↗

PubMed2000

Amplitude curves and operating regimes in dynamic atomic force microscopy

The experimental dependence of the amplitude on the average tip-sample distance has been studied to understand the operation of an atomic force microscope with an amplitude modulation feedback. The amplitude curves can be classified in three major groups according to the existence or not of a local maximum and how the maximum is reached (steplike discontinuities vs. smooth transitions). A model describing the cantilever motion as a forced nonlinear oscillator allows to associate the features observed in the amplitude curves with the tip-sample interaction force. The model also allows to define two elemental tip-sample interaction regimes, attractive and repulsive. The presence of a local maximum in the amplitude curves is related to a transition between the attractive and the repulsive regime.

Journal Article↗

PubMed2000

Purification and some properties of catalase from wheat germ (Triticum aestivum L.).

Two isoforms of catalase, CAT-1 and CAT-2, were purified from wheat germ after extraction, ammonium sulfate precipitations, hydrophobic chromatography, and two ionic-exchange chromatographies. The global yields and the purification factors were close to 3% and 50 for CAT-1 and close to 6% and 100 for CAT-2. Both isoforms exhibit an optimum activity at pH 7. When pH was decreased from 7 to 5.6, CAT-1 showed a decreasing affinity for its substrate, whereas the opposite was found for CAT-2. Both isoforms were irreversibly denaturated when exposed to acidic pH, CAT-1 being more sensitive than CAT-2. Conversely, CAT-2 appeared to be more sensitive to inhibitors. The rate as well as the extent of denaturation during incubation with 3-amino-1,2,4-triazole (AT) were higher with CAT-2 than with CAT-1. Guaiacol is a competitive inhibitor more potent with respect to CAT-2. The difference in affinity for hydrogen peroxide as well as the poor stability of CAT-1 in acidic medium suggests that this isoform could be less effective during dough mixing.

Catalase↗

PubMed2000

Potentiation of conditioned freezing following dorsomedial prefrontal cortex lesions does not interfere with fear reduction in mice.

In Experiment 1, an auditory conditioned stimulus (CS) was paired with footshock, except when it was preceded by another stimulus (a visual conditioned inhibitor [CI]). After conditioning, all mice displayed less CS-evoked freezing when the CI-CS compound was presented than when the CS was presented alone. However, lesions of the dorsomedial prefrontal cortex (dmPFC) potentiated CS-evoked freezing on each of the 2 sessions (i.e., CI CS and CS alone). In Experiment 2, mice were submitted to fear extinction (CS-alone presentation for 3 days). Lesioned mice exhibited a higher level of freezing behavior than controls on each of the 3 sessions. However, lesioned mice and controls displayed the same rate of reduction of freezing over the 3 days of extinction. These data in mice support previous studies in rats, which suggests that the dmPFC is not critical for either conditioned inhibition or extinction of acquired freezing behavior.

Animals↗

PubMed2000

A survey of academic departments of emergency medicine regarding operation and clinical practice.

STUDY OBJECTIVE: To survey academic departments of emergency medicine concerning their operation and clinical practice. METHODS: A survey was mailed to the chairs of all 56 academic departments of emergency medicine in the United States requesting information concerning operations and clinical activity in budget year 1997-1998 compared with 1995-1996. These results were then compared with a similar survey conducted in the fall of 1996, examining the 1995-1996 academic year compared with the 1994-1995 academic year. RESULTS: Forty-one (73%) academic departments of emergency medicine responded. For 1997-1998, compared with 1995-1996, 24 (59%) academic departments of emergency medicine reported an increase in emergency department patient volume; 10 (24%) reported a decrease. Twenty-four (51%) academic departments of emergency medicine reported an increase in ED patient severity, whereas 7 (15%) reported a decrease. Twenty-five (61%) academic departments of emergency medicine reported an increase in net clinical revenue for emergency medicine services, and 9 (22%) reported a decrease. Only 9 (22%) academic departments of emergency medicine reported other academic departments within their university/medical center aggressively directing patients away from the ED compared with 14 (30%) in the previous study. The percentage of academic departments of emergency medicine using midlevel providers remained essentially the same over time (68% versus 66%). In both studies, midlevel providers were used most commonly in a fast-track setting. Only 37% of academic departments of emergency medicine reported having an observation unit; staffing in all cases was by emergency physicians. Since the last survey, 38 (93%) academic departments of emergency medicine reported their medical center or hospital negotiating with managed care organizations to provide services. Unfortunately, only 41% of chairs were involved in these discussions. Between January 1, 1997, and the 1998 fall survey, 29% of academic departments of emergency medicine reported their university merging with another university system, and 19% reported such mergers being discussed. Similarly, between January 1, 1997, and fall 1998, 22% of academic departments of emergency medicine reported their institution merging with a private entity, whereas 16% reported ongoing discussions. CONCLUSION: Academic departments of emergency medicine have experienced some encouraging trends: an increase in ED patient volume, patient severity, and net clinical revenue during the study period. Midlevel providers continue to be used primarily in fast-track areas of EDs. An area of potential growth for academic departments of emergency medicine is observation medicine, because only one third of academic departments of emergency medicine have such a unit. Academic medical centers have experienced a significant increase in merger activity during the study period.

Academic Medical Centers↗

PubMed2000

Renal angiotensin II receptors and protein kinase C in diabetic rats: effects of insulin and ACE inhibition.

It has been shown that glomerular ANG II receptors are downregulated and protein kinase C (PKC) activity is enhanced in diabetes mellitus. Therefore, we investigated glomerular and preglomerular vascular ANG II receptors and PKC isoform regulation in streptozotocin (STZ)-diabetic rats treated with insulin and/or captopril. Diabetic rats were prepared by injecting STZ (60 mg/kg). Those that developed diabetes after 48 h were treated with low or high doses of insulin, or with a low dose of insulin as well as captopril, and killed 14 days later. Their glomeruli and preglomerular vessels were purified, competitive binding studies were performed by using the ANG II antagonists losartan and PD-123319, and PKC analysis was carried out by Western blotting. Competitive binding studies showed that the AT(1) receptor was the only ANG II receptor detected on both glomeruli and preglomerular vessels of all groups. Preglomerular vascular AT(1) receptor density (B(max)) was significantly upregulated in low insulin-treated STZ rats, whereas glomerular AT(1) B(max) was downregulated. Furthermore, both the captopril- and high insulin-treated groups had less glomerulosclerosis and vascular damage than the low insulin-treated group. PKCalpha, PKCdelta, PKCepsilon, and PKCmu isoforms found in preglomerular vessels were upregulated by captopril and high insulin doses, respectively, whereas no such regulation occurred in glomeruli. We conclude that in STZ-diabetic rats ANG II receptors and PKC isoforms on preglomerular vessels and glomeruli are differentially regulated by treatment with insulin and/or captopril.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed2000

Carcinosarcoma in a bladder diverticulum. A case report and literature review.

Carcinosarcoma of the bladder is a rare neoplasm composed of a mixture of malignant epithelial and mesenchymal components. The presentation and clinical course of an infiltrating carcinosarcoma located in a bladder diverticulum coexisting with prostatic adenocarcinoma in a 69-year-old man are described. We believe this to be the fifth report of true carcinosarcoma appearing in a bladder diverticulum.

Adenocarcinoma↗

PubMed2000

Piecemeal degranulation of peripheral blood eosinophils: a study of allergic subjects during and out of the pollen season.

The variability of serum and plasma levels of eosinophil granule proteins in different clinical conditions, interpreted as the result of different patterns of cytokine priming, suggests a selective mobilization of granule proteins. Inasmuch as piecemeal degranulation (PM) is the mechanism proposed for the differential release of eosinophil granule proteins, we decided to investigate whether blood eosinophils from allergic subjects show characteristics of PM during natural allergen challenge. Eosinophils from three birch-sensitive subjects were studied before and during the pollen season. Electron microscopy analysis showed that during the season, eosinophils presented morphologic features of PM. By immunogold labeling, eosinophil cationic protein (ECP) was detected not only in normal specific granules but also in the cytoplasm, in the vicinity of partially lucent specific granules. These results were confirmed by subcellular fractionation, where the amount of ECP associated with compartments containing small vesicles increased 2-fold during the pollen season. A study of the distribution of ECP, eosinophil peroxidase, and hexosaminidase in eosinophils of different densities showed that the profile of each of these proteins differed depending on cell density. All of these proteins decreased in the specific granule of hypodense cells and increased in other cell compartments. We conclude that allergen exposure causes PM of the peripheral blood eosinophils of allergic subjects, and that the density of these cells reflects the degree of degranulation. Our results provide novel information for the understanding of the selective mobilization of granule proteins into the circulation.

Blood Proteins↗

PubMed2000

Intracellular studies of the nucleoside reverse transcriptase inhibitor active metabolites: a review.

Nucleoside reverse transcriptase inhibitors (NRTIs) plasma concentrations do not correlate with clinical efficacy or toxicity. These agents need to be phosphorylated to become active against HIV-infection. Thus, the characterization of the NRTIs intracellular metabolite pharmacological parameters will provide a better understanding that could lead to the development of more rational dose regimens in the HIV-infected population. Furthermore, intracellular measurements of NRTIs may provide a better marker with respect to clinical efficacy and toxicity than plasma concentrations. Thus, in this article we review the latest information regarding the intracellular pharmacological parameters of zidovudine (ZDV) and lamivudine (3TC) active metabolites in HIV-infected patients including the results from our recent clinical studies. We will start the discussion with ZDV and 3TC clinical efficacy, followed by systemic pharmacokinetics studies. We will then discuss the in vitro and in vivo intracellular studies with particular emphasis in the method development to measure these metabolites and we will conclude with the most current data from our clinical trials.

Adult↗

PubMed2000

Lateral extra-articular knee reconstruction: long-term patient outcome and satisfaction.

Fifty-two patients who had an extraarticular reconstruction for anterior cruciate ligament (ACL) insufficiency were interviewed at an average of 11.4 years after their reconstruction. During the follow-up period, 4 patients (8%) had intra-articular reconstructions for persistent instability or re-injury, and another 4 (8%) had arthroscopic surgery for meniscal lesions. The mean Lysholm score at follow-up was 76.9. Of the 52 patients, 5 had had subsequent surgery during the follow-up period. In the remaining 47 patients, the results were excellent in 14 (29%), good in 10 (23%), fair in 7 (15%), and poor in 16 (33%). Patients operated on acutely (<6 weeks after injury) had a mean score of 82, whereas patients operated on more than 6 weeks after injury had a mean score of 75. Adding those patients who required subsequent reconstructions for persistent instability (4 knees) and those who obtained fair and poor results yielded an alarming rate of unsatisfactory results (52%). On the basis of these findings, we believe the lateral extraarticular reconstruction is not an acceptable form of treatment for the functionally unstable knee.

Adolescent↗

PubMed1999

The amygdala modulates prefrontal cortex activity relative to conditioned fear.

Animals learn that a tone can predict the occurrence of an electric shock through classical conditioning. Mice or rats trained in this manner display fear responses, such as freezing behaviour, when they hear the conditioned tone. Studies using amygdalectomized rats have shown that the amygdala is required for both the acquisition and expression of learned fear responses. Freezing to a conditioned tone is enhanced following damage to the dorsal part of the medial prefrontal cortex, indicating that this area may be involved in fear reduction. Here we show that prefrontal neurons reduce their spontaneous activity in the presence of a conditioned aversive tone as a function of the degree of fear. The depression in prefrontal spontaneous activity is related to amygdala activity but not to the freezing response itself. These data indicate that, in the presence of threatening stimuli, the amygdala controls both fear expression and prefrontal neuronal activity. They suggest that abnormal amygdala-induced modulation of prefrontal neuronal activity may be involved in the pathophysiology of certain forms of anxiety disorder.

Amygdala↗