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Biomedical subjects

R Garcia

Publications and source records attributed to R Garcia.

At least 217 records · Page 12Linked to original sources

Human nasal mucosal changes after exposure to urban pollution.

Millions of people worldwide are living in areas where ozone (O3) concentrations exceed health standards (an hourly average of 235 micrograms/m3/0.12 ppm, not to be exceeded more than once per year). Ozone induces acute nasal inflammatory responses and significant epithelial lesions in experimental animals and humans. To determine the nasal effects of a 15-day exposure to an urban polluted atmosphere with O3 as the main pollutant, we studied a population of healthy, young males newly arrived to southwest metropolitan Mexico City (SWMMC). The study included 49 non-smoking residents in an unpolluted port, Veracruz City; 14 subjects stayed in the port and served as controls, while 35 subjects traveled to SWMMC and had serial nasal lavages at different times after arriving in SWMMC. Subjects had exposures to ambient O3 an average of 10.2 hr/day, with a total cumulative O3 exposure of 10.644 ppm.hr. Nasal inflammatory responses, polymorphonuclear leukocyte PMN-CD11b surface expression, rhinoscopic changes, and respiratory symptoms were evaluated. Exposed subjects had massive nasal epithelial shedding and significant responses in PMN nasal influx (p < 0.00001) and in PMN-CD11b expression (p < 0.05). Cumulative O3 exposure correlated with respiratory symptoms, PMNs (rs = 0.2374, p < 0.01), and CD11b (rs = 0.3094, p < 0.01); 94% of exposed subjects experienced respiratory symptoms, and 97% left the city with an abnormal nasal mucosa by rhinoscopy. Nasal epithelial changes persisted 2 weeks after the exposed subjects returned to their nonpolluted environment. Exposure to an urban polluted atmosphere induces significant and persistent nasal epithelial alterations in healthy subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Utilization of dental services as a risk factor for periodontitis.

The relation between utilization of dental services from community dentists and the extent and severity of alveolar bone loss is reported for a panel of men followed for over 6 years. Oral health data were collected by the Department of Veterans Affairs, Dental Longitudinal Study, which began in 1969 and still continues. Participants have received regular oral examinations approximately every 3 years. A variety of oral health conditions were assessed, including plaque, calculus, gingival inflammation, probing depth, tooth mobility, clinical attachment level, and alveolar bone loss. Utilization data were abstracted from the dental records of dental offices that participants attended from 1979 through 1988. Multivariate modeling as well as comparisons of high utilizers and non-utilizers indicate that utilization of routine diagnostic and preventive services was not predictive of the extent and severity of periodontitis.

Alveolar Bone Loss↗

Purification and characterization of a human neutrophil lipocalin (HNL) from the secondary granules of human neutrophils.

A 45 kDa-protein was purified from the granules of human neutrophils. The protein consists of two apparently identical subunits. The isoelectric point was pH 8.40, and the molecular weight 45 kDa (unreduced) or 24 kDa (reduced). Treatment of the protein with Endoglucosidase F resulted in a reduction in the molecular weight to 20 kDa, indicating the presence of N-linked carbohydrate. The extinction coeffient was E1%,1cm = 13.76 at 280 nm. The 60 amino acid sequence revealed up to 65% sequence homology with rat alpha 2-microglobulin-related protein, which belongs to the lipocalin family. The protein co-sedimented with secondary (specific) granule marker proteins and correlated to the neutrophil content of Lactoferrin (r = 0.81, p < 0.001) and was estimated to be 0.59 microgram 10(-6) cells. Release studies showed that the neutrophils released 51.4 +/- 9.0% of the total cellular content of the protein when they were exposed to serum-opsonized particles, which was much higher than the release of Myeloperoxidase (12.7 +/- 3.5%) and Lactoferrin (22.9 +/- 4.7%). The N-terminal and four tryptic fragment amino acid sequence of the protein was identical with an N-formyl peptide binding 24 kDa protein and gelatinase associated protein of human neutrophils. In conclusion, we have purified and characterized a protein, human neutrophil lipocalin (HNL), from the secondary granules of human neutrophils and shown that it is readily mobilized from the neutrophils upon stimulation.

Acute-Phase Proteins↗

Rat renal preglomerular vessels, glomeruli and papillae do not express detectable quantities of B-type natriuretic peptide receptor.

DESIGN: Atrial natriuretic factor (ANF) receptor subtypes were quantitated by radioligand studies in three different rat renal isolated tissues: preglomerular vessels, glomeruli and papillae. RESULTS: In preglomerular vessels 100% of [125I]-ANF binding was displaced with high affinity by ANF. C-ANF (des-[Gln18,Ser19,Gly20,Leu21,Gly22]ANP(4- 23)) a specific ligand for ANP-C receptors, displaced 30% of total binding with a lower affinity than ANF. C-type natriuretic peptide (CNP) displaced [125I]-ANF binding in a biphasic manner, indicating that it binds to two sites with affinities three orders of magnitude apart. When CNP was incubated in the presence of 0.1 mumol/l C-ANF to saturate ANP-C receptors, the high-affinity binding site vanished and maximum binding decreased to 70%, suggesting that CNP binds with high affinity to ANP-C receptors. Since the ANP-A receptor has little or no avidity for CNP, it is probably the low-affinity binding site. CNP and C-ANF displaced most [125I]-[Tyr]CNP(1-22) binding with very close affinities, indicating that CNP binds primarily preglomerular vascular ANP-C receptors. In glomeruli CNP behaved similarly to C-ANF in its ability to displace approximately 85% of [125I]-ANF binding; the remaining 15% was completely displaced by ANF. C-ANF and CNP inhibited 100% of [125I]-[Tyr]CNP(1-22) binding. Both findings suggest that [125I]-[Tyr]CNP(1-22) binds ANP-C receptors exclusively. In renal papillae no displacement of [125I]-ANF by C-ANF was observed, and CNP was bound to ANP-A receptors with the same very low affinity as in preglomerular vessels. The absence of [125I]-[Tyr]CNP(1-22) binding to papillary membranes indicates that ANP-B receptors are not expressed in that tissue. Unlike ANF, CNP stimulated cGMP production in glomeruli and papillae only at extremely high, supraphysiological concentrations. CONCLUSION: The present results suggest that ANP-B receptors either are absent or are present in undetectable amounts in rat renal preglomerular vessels, glomeruli and papillae.

Animals↗

Spatial discrimination learning induces LTP-like changes in the lateral septum of mice.

The efficacy of synaptic transmission from the fimbria to the lateral septum (LS) of freely moving mice was monitored electrophysiologically over 9 days of training in a spatial discrimination task (radial maze). Electrical stimulation of the fimbria evoked two negative waves (N2 and N3) in the ipsilateral LS. Compared to a control group exposed to muscular effort (treadmill), trained animals displayed a significant and progressive increase in the amplitude of N3 with no changes in N2. Moreover, this increase was of greater magnitude in fast learners than in slow learners and persisted for at least 24 h following the last (9th) training session. These changes might play a role in spatial learning through the regulation of septohippocampal cholinergic activity.

Animals↗

A comparative study of age-related changes in inhibitory processes and long-term potentiation in the lateral septum of mice.

Anaesthetized C57 BL/6 mice of different ages (young: 5 months; middle-aged: 15 months; and old: 21 months) were used to determine whether aging alters the efficiency of synaptic inhibition and long-term potentiation (LTP) in the lateral septum (LS). Electrical stimulation of the fimbria induced field potentials in the ipsilateral LS comprising two initial negative components (N2 and N3) followed by a positive wave of low amplitude. Paired-pulse experiments showed a facilitation of the N2 component and a concomitant depression of the N3 components. Facilitation of the N2 component was stronger in both middle-aged and old mice as compared to young mice, whereas an inverse pattern of changes was observed for inhibition of the N3 component. High-frequency stimulation of the fimbria produced a persistent increase in the N3 amplitude. This LTP was of significantly higher amplitude in both young and middle-aged mice as compared to old mice. These results suggest that aging impairs both inhibitory processes and synaptic plasticity in the mouse LS, but that inhibitory processes appear to be affected earlier.

Aging↗

Cationic liposome-mediated incorporation of prostatic acid phosphatase protein into human prostate carcinoma cells.

Lipofectin, the commercially available cationic liposome, was used to introduce the purified prostatic acid phosphatase protein into the established human prostate carcinoma cells. The incorporated phosphatase protein which retained its enzymatic activity as demonstrated by the tartrate-sensitive acid phosphatase assay was localized in the cytoplasm by immunofluorescence staining. Further, cells that were treated with phosphatase/Lipofectin complexes expressed a decreased phosphotyrosine level, presumably due to the endogenous protein tyrosine phosphatase activity of the acid phosphatase protein. A cationic liposome such as lipofectin may thus be employed to mediate transport of other acidic proteins into cells, providing a way to examine their biological functions in vivo.

Acid Phosphatase↗

Oral prostaglandin E2 prevents gut atrophy during intravenous feeding but not bacterial translocation.

The pathophysiologic changes in gut physiology that result in bacterial translocation during intravenous feeding are poorly defined, though believed to be related in part to intestinal atrophy, decreased mesenteric blood flow, and lack of intestinal secretions. This study investigated the hypothesis that pharmacologic preservation of intestinal structure and function by orally administered 16,16-dimethyl-prostaglandin E2 would prevent bacterial translocation in intravenously fed rats. Thirty-five rats were randomized to three groups: group 1 was fed rat chow ad libitum, group 2 received standard parenteral nutrition, and group 3 received parenteral nutrition plus oral 16,16-dimethyl-prostaglandin E2 (150 micrograms/kg twice a day). Rats were fed there respective diets for 5 days and killed. Mesenteric lymph nodes were procured for culture, and the intestine was assessed for weight, DNA, protein values, and histologic character. Results demonstrate that orally administered 16,16-dimethyl-prostaglandin E2 potently attenuates the intestinal atrophy associated with parenteral feeding but does not prevent bacterial translocation. Intestinal barrier dysfunction and bacterial translocation during intravenous feeding is related to factors other than the development of gut atrophy.

Administration, Oral↗

Family pesticide use and childhood brain cancer.

The relationship between family pesticide use and childhood brain cancer was examined in a case-control study. Telephone interviews were conducted from June 1989 through March 1990 with the natural mothers of 45 childhood brain cancer cases, 85 friend controls, and 108 cancer controls. In comparisons to friend controls, significant positive associations were observed for use of pesticides to control nuisance pests in the home, no-pest-strips in the home, pesticides to control termites, Kwell shampoo, flea collars on pets, diazinon in the garden or orchard, and herbicides to control weeds in the yard. In comparisons to cancer controls, significant positive associations were observed for use of pesticide bombs in the home, pesticides to control termites, flea collars on pets, insecticides in the garden or orchard, carbaryl in the garden or orchard, and herbicides to control weeds in the yard. In general, positive associations in comparisons to one control group were supported by elevated odds ratios in comparisons to the other control group. Several potentially important associations were identified in this study. However, small sample sizes, potential recall bias, multiple comparisons, and lack of detailed exposure verification require further research to confirm these findings.

Brain Neoplasms↗

Characterisation of plasma and tissue atrial natriuretic factor during development of moderate high output heart failure in the rat.

OBJECTIVE: The aims were (1) to characterise plasma and tissue atrial natriuretic factor (ANF) levels, haemodynamic variables, and renal function at different stages of moderate chronic high output heart failure in the rat; and (2) to assess the contribution of the atria and ventricles to plasma ANF levels. METHODS: Plasma and tissue ANF levels, haemodynamics, and renal function were evaluated at 1, 2, 4, 8, and 16 weeks after the development of aorto-caval shunts. Sham operated animals served as controls at identical time points. Male Sprague-Dawley rats weighing 225-275 g were used in all experiments. RESULTS: Mean arterial blood pressure was lower and right atrial pressure was higher in the aorto-caval shunt groups than in sham operated controls at all time periods. Left ventricular end diastolic pressure was increased significantly in aorto-caval shunt rats at 1, 2, and 4 weeks when compared with their control counterparts. Plasma COOH terminal and NH2 terminal ANF concentrations were increased significantly in aorto-caval shunt animals. Plasma ANF was positively correlated with right atrial pressure and left ventricular end diastolic pressure in aorto-caval shunt rats but not in sham operated controls. Aorto-caval shunt animals also developed marked cardiac hypertrophy with decreased atrial ANF concentration, but not content, and increased ventricular ANF concentration and content. Despite high plasma ANF concentrations, aorto-caval shunt rats had a lower packed cell volume at all observed periods and reduced urinary sodium excretion and urinary volume at 1 and 2 weeks, with trends to a reduction at 4, 8, and 16 weeks. Body weight was higher in aorto-caval shunt animals at 16 weeks than in sham operated controls. CONCLUSIONS: (1) Chronically increased cardiac filling pressure stimulated not only ANF release but also ANF synthesis in each cardiac chamber, which in turn contributed to raised plasma ANF concentrations in aorto-caval shunt rats; (2) an attenuated renal response to endogenous ANF and sodium and water retention were apparent in A-C shunt rats. Activation of neurohormonal vasoconstrictor systems and gradually decreased plasma ANF concentrations may contribute to sodium and water retention at different stages of this experimental model of heart failure.

Animals↗

Heterogeneous regulation of renal atrial natriuretic factor receptor subtypes in one-kidney, one clip hypertensive rats.

OBJECTIVES: To investigate the regulation of papillary atrial natriuretic factor (ANF) receptors and the differential regulation of glomerular ANF receptor subtypes in one-kidney, one clip (1-K,1C) hypertension. METHODS: Plasma immunoreactive ANF levels and atrial and ventricular ANF content were measured in 1-K,1C rats and their normotensive uninephrectomized controls. Glomerular and papillary ANF receptor subtypes were characterized by competitive radioligand binding assay. Stimulation of cyclic GMP (cGMP) production, by increasing ANF doses, was examined in isolated glomeruli. RESULTS: Plasma amino-terminal ANF levels were higher in 1-K,1C than in control rats. ANF concentrations in the left atrium were lower and ventricular ANF concentrations were higher in the 1-K,1C group. Competition binding curves for glomerular membranes revealed the presence of two binding sites (ANF-R1 and ANF-R2) in both groups. Total glomerular ANF receptor density was lower in 1-K,1C rats than in their normotensive controls. Both receptor subtypes were downregulated in 1-K,1C rats and their relative proportion was similar to that in glomerular preparations from the controls. ANF-stimulated cGMP production by isolated glomeruli was lower in 1-K,1C than in normotensive rats. In papillary membranes, ANF was bound to a homogeneous population of high-affinity binding sites in both groups. A modest augmentation in the density of papillary ANF receptors was observed in 1-K,1C rats. CONCLUSION: Glomerular and papillary ANF receptors may be regulated differently in the presence of elevated plasma ANF levels. The present results indicate that the downregulation of glomerular ANF-R1 and the reduced cGMP response may lead to altered sodium and water handling by the kidney of 1-K,1C hypertensive rats.

Animals↗

Characterization of receptors for the atrial natriuretic factor in rat renal microvessels.

OBJECTIVE: To characterize [125I]-atrial natriuretic factor [ANF-(99-126)] binding sites in the renal preglomerular microvasculature of Sprague-Dawley rats. METHODS: Renal preglomerular microvessels were isolated by infusion of a magnetized iron oxide solution into the renal arteries and detachment from non-vascular tissue by a magnetic field. In order to characterize [125I]-ANF-(99-126) binding sites, saturation and competitive binding experiments were performed. To evaluate the proportions of ANF receptor subtypes (ANF-R1, ANF-R2), competition curves were charted in the presence of 10(-6) mol/l C-ANF-(4-23), a specific ligand of ANF-R2 (ANP-C). RESULTS: [125I]-ANF binding to vascular membranes was saturable and of high affinity. Equilibrium saturation binding curves suggested the presence of one group of high-affinity receptors [equilibrium dissociation constant (Kd) 22 +/- 6 pmol/l; binding capacity (Bmax) 118 +/- 6 fmol/mg protein]. In competitive inhibition experiments, no significant differences were found in binding capacity between experiments performed either in the presence or in the absence of an excess (1 mumol/l) of C-ANF (94 +/- 27 versus 151 +/- 35 fmol/mg protein, respectively), suggesting that most receptors in the renal vasculature are of the subtype ANF-R1. Incubation of renal microvessels with ANF-(99-126) stimulated cyclic GMP production in a dose-related manner. In parallel studies, the proportion of ANF-R1 (ANP-A, -B) and ANF-R2 (ANP-C) receptors in glomeruli, calculated from competitive inhibition experiments, was 86 +/- 2 and 14 +/- 2%, respectively (P < 0.005). CONCLUSIONS: These results indicate that rat renal preglomerular microvessels contain a high proportion of guanylate cyclase-coupled ANF-R1 (ANP-A, -B) and a low density of ANF-R2 (ANP-C) receptors. This difference in the proportion of ANF receptor subtypes, compared to that reported in glomeruli and other vascular beds, may have physiological significance.

Animals↗

ZD1542, a potent thromboxane A2 synthase inhibitor and receptor antagonist in vitro.

1. The thromboxane A2 synthase (TXS) inhibitory activity and the thromboxane A2 (TP)-receptor blocking action of ZD1542 (4(Z)-6-[2S,4S,5R)-2-[1-methyl-1-(2-nitro-4-tolyloxy)ethyl]-4-(3- pyridyl)-1,3-dioxan-5-yl]hex-4-enoic acid) has been evaluated in vitro on platelets and whole blood from a range of species including man. Antagonist activity has also been investigated in vascular and pulmonary smooth muscle preparations in vitro. 2. ZD1542 caused concentration-dependent inhibition of human platelet microsomal thromboxane B2 (TXB2) production in vitro (IC50 = 0.016 microM); this inhibition was associated with an increase in prostaglandin E2 (PGE2) and PGF2 alpha formation. 3. ZD1542 also inhibited collagen-stimulated TXS in human, rat and dog whole blood giving IC50 values of 0.018, 0.009 and 0.049 microM respectively. The drug did not modify platelet cyclo-oxygenase activity as inhibition of TXB2 formation was associated with a concomitant increase in the levels of PGD2, PGE2 and PGF2 alpha. ZD1542 had little if any effect against cultured human umbilical vein endothelial cell (HUVEC) cyclo-oxygenase (IC50 > 100 microM) and prostacyclin (PGI2) synthase (IC50 = 18.0 +/- 8.6 microM). 4. ZD1542 caused concentration-dependent inhibition of U46619-induced aggregation responses of human, rat and dog platelets yielding apparent pA2 values of 8.3, 8.5 and 9.1 respectively. The drug was selective as, at concentrations up to 100 microM, it did not modify 5-hydroxytryptamine (5-HT) or the primary phases of adenosine diphosphate (ADP) and adrenaline-induced aggregation. Furthermore, ZD1542 (100 microM) modified only weakly the platelet effects of PGD2, PGE1 and PGI2. 5. ZD1542 also caused concentration-dependent inhibition of U46619-mediated contractions of rat thoracic aorta, guinea-pig trachea and lung parenchyma preparations giving apparent pA2 values of 8.6,8.3 and 8.5 respectively. At concentrations approaching three orders of magnitude greater than those required to block U46619-mediated contractions, the drug did not affect the actions of non-prostanoid agonists or exhibit agonist activity in any of the smooth muscle preparations employed; neither did it interact at EP- or FP-receptors.6. In conclusion, the present study demonstrates that ZD1542 is a drug that exhibits both potent,selective TXS inhibition and TXA2 receptor antagonism.

Animals↗

Lack of expression of intercellular adhesion molecule ICAM-1 in lepromatous leprosy patients.

It is conceivable that an abnormal expression of cell-adhesion molecules can contribute to the poor inflammatory response seen in some inflammatory skin diseases. Adhesins are cell-surface molecules that are expressed by many cell types. The main function of adhesins appears to be the promotion of cellular interactions, such as those occurring between immune cells. The epidermis of patients with inflammatory skin diseases exhibits an increased expression of ICAM-1, and it has been postulated that such increased expression can be important in the genesis of cutaneous inflammation. The expression of cell-adhesion molecules (LFA-1, LFA-2, LFA-3 and ICAM-1) in skin lesions of leprosy patients was studied, as well as the in vitro expression of these molecules induced with gamma interferon (IFN-gamma). A lack of expression of ICAM-1 in the epidermis of lepromatous patients was noted; in addition, no expression of ICAM-1 was seen in the nearly normal skin from these patients incubated with IFN-gamma. A similar expression of the four molecules studies was noted in the dermis of both the lepromatous and tuberculoid types of leprosy. The epidermis of the lepromatous leprosy patients appears to have a defective expression of ICAM-1.

Antigens, CD↗

[Mesothelial cell. Cytology. Cytochemistry. Immunocytochemistry. Contribution of immunolabelling to the cytodiagnosis of serous effusions with cells of mesothelial aspect].

This paper reviews the contribution of cytochemical and immunocytochemical methods to the cytodiagnosis of serous fluids. For this purpose, 1000 fluids were reviewed (500 pleural and 500 peritoneal samples). The most reliable histochemical technique is the iron stain which labels macrophages. A minimum immunolabelling panel (including one or two epithelial markers and vimentin), applied to the identification of the usual phenotypes of reactive fluids with mesothelial cells or with macrophages, to adenocarcinomatous fluids and to malignant mesothelioma fluids, is proposed. The sensitivity and specificity of the reaction is discussed but, altogether the value of the method appeared rather limited as a correct diagnosis was obtained in 95% of cases by a careful morphological study.

Adenocarcinoma↗

Migration of grafted rat astrocytes: dependence on source/target organ.

Neonatal rat cortical astrocytes migrate extensively after transplantation into the brains of adult hosts. However, the effects of cues provided by different sources of donor astrocytes and by different target sites of implantation on this migration is unknown. In order to investigate the significance of regional influences on glial migration, we established primary cultures of astrocytes derived from 1-3 day old rat cerebral cortex, hippocampus, and hypothalamus. After in vitro labelling with either Fast Blue or fluorescein-labelled latex beads, these astrocytes were inoculated into different target regions of the adult rat brain by stereotaxic injection with a Hamilton syringe. Astrocytes implanted into the cerebral cortex migrated extensively throughout the adult brain regardless of their donor source. These implanted cells were intimately associated with the ventricular wall, glial limitans, vasculature, and fiber bundles. Astrocytes homografted into the hippocampus and the hypothalamus migrated primarily within and around the respective homotopic target organs. Migration of astrocytes derived from cerebral cortex was also limited when injections were made into these two regions. In these latter cases, migration appeared to be less guided by other cellular or regional cues than was migration after implantation into the cerebral cortex. These results suggest that the migration patterns of astrocytes grafted after tissue culture are more dependent on the target implantation site than on the donor organ.

Animals↗