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Biomedical subjects

R Romero

Publications and source records attributed to R Romero.

At least 235 records · Page 13Linked to original sources
PubMed1997

High expression of tumor necrosis factor-alpha and interleukin-6 in periventricular leukomalacia.

OBJECTIVE: Periventricular leukomalacia, a common neonatal brain white matter lesion, is a major risk factor for cerebral palsy. Subclinical chorioamnionitis is a risk factor for the development of periventricular leukomalacia, and inflammatory cytokines have been implicated as central mediators of brain injury in this disorder. To elucidate the relationship between the local expression of cytokines and periventricular leukomalacia, we studied neonatal brains to determine whether high expression of tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-6 was observed in these lesions. STUDY DESIGN: Immunohistochemical staining for cytokines (tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-6) was performed in 10% formalin-fixed, paraffin-embedded brain sections of 17 cases with periventricular leukomalacia. Specimens were obtained from autopsies performed between 1987 and 1994. Brain sections from 17 cases of neonatal deaths without periventricular leukomalacia lesions matched for gestational age at birth, duration of postnatal survival, and presence or absence of infection-related morbidity were used as controls. RESULTS: The expression of tumor necrosis factor-alpha, interleukin-1 beta, or interleukin-6 was demonstrated in 88% (15/17) of cases with and in 18% (3/17) of cases without periventricular leukomalacia (p < 0.001). Cytokines were expressed mainly in hypertrophic astrocytes and microglial cells. The expression of tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-6 was identified in 82% (14/17), 29% (5/17), and 71% (12/17) of cases of periventricular leukomalacia, respectively. However, a significantly lower proportion of cases without periventricular leukomalacia expressed tumor necrosis factor-alpha (18%, 3/17) and interleukin-6 (6%, 1/17) than those with the disorder (p < 0.005 for each). CONCLUSIONS: Expression of tumor necrosis factor-alpha and interleukin-6 was observed more frequently in brain lesions with periventricular leukomalacia than in those without periventricular leukomalacia. These findings provide strong support for the hypothesis that proinflammatory cytokines play a role in the genesis of periventricular leukomalacia.

Brain Chemistry↗
PubMed1997

Experimentally induced intrauterine infection causes fetal brain white matter lesions in rabbits.

OBJECTIVE: Periventricular leukomalacia, a common brain white matter lesion in preterm neonates, is a major risk factor for cerebral palsy. Epidemiologic studies have demonstrated an association between infection and periventricular leukomalacia. The purpose of this study was to determine whether ascending intrauterine infection could cause brain white matter lesions in the fetal rabbit. STUDY DESIGN: Rabbits with timed pregnancies underwent hysteroscopy at 20 to 21 days of gestation (70%). Animals were allocated in a ratio of 2:1 for inoculation with either Escherichia coli (0.2 ml containing 10(3) to 10(4) colony-forming units) or sterile saline solution. Both groups were treated with ampicillin-sulbactam (Unasyn, 100 mg/kg per day; Pfizer, Seoul) every 8 hours until they were killed 5 to 6 days after hysteroscopy. Histologic examination of the placentas and fetal brains was conducted. RESULTS: Forty-five animals underwent hysteroscopy; 31 were inoculated with E. coli and 14 with sterile saline solution. At the time the animals were killed, the rate of intrauterine infection was higher and there were fewer live fetuses in the E. coli-inoculated animals than in the saline solution group. Histologic evidence of brain white matter damage was identified in 12 fetuses born to 10 E. coli-inoculated rabbits but none in the saline solution group (p < 0.05). All rabbits with brain white matter lesions had evidence of intrauterine infection. Evidence of white matter damage included increased karyorrhexis, rarefaction, and disorganization of white matter. Apoptosis was demonstrated in areas of white matter damage by immunohistochemical studies. CONCLUSION: Experimental ascending intrauterine infection can cause fetal brain white matter lesions.

Animals↗
PubMed1997

Amniotic fluid cytokines (interleukin-6, tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-8) and the risk for the development of bronchopulmonary dysplasia.

OBJECTIVE: Our purpose was to test the hypothesis that neonates who develop bronchopulmonary dysplasia have higher amniotic fluid concentrations of proinflammatory cytokines than those who do not develop bronchopulmonary dysplasia. STUDY DESIGN: The relationship between amniotic fluid concentrations of interleukin-6, tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-8 and the occurrence of bronchopulmonary dysplasia in the neonate was examined in 69 patients who were delivered of preterm neonates (< or = 33 weeks) within 5 days of amniocentesis. Cytokines were measured by specific immunoassays. RESULTS: Bronchopulmonary dysplasia was diagnosed in 19% (13/69) of newborns. Median amniotic fluid concentrations of interleukin-6, tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-8 concentrations were significantly higher in mothers whose infants had bronchopulmonary dysplasia than in mothers whose infants did not have bronchopulmonary dysplasia (p < 0.05 for each). Neonates who had bronchopulmonary dysplasia were delivered at earlier gestational ages and had lower birth weights than those without bronchopulmonary dysplasia. The differences in median amniotic fluid interleukin-6, interleukin-1 beta, and interleukin-8 between these two groups remained significant after we adjusted for the effect of gestational age at birth (p < 0.05 for each). CONCLUSIONS: (1) Antenatal exposure to proinflammatory cytokines is a risk factor for the development of bronchopulmonary dysplasia; (2) the injury responsible for bronchopulmonary dysplasia in a subset of neonates may begin before birth.

Adult↗
PubMed1997

Amniotic fluid inflammatory cytokines (interleukin-6, interleukin-1beta, and tumor necrosis factor-alpha), neonatal brain white matter lesions, and cerebral palsy.

OBJECTIVE: Ultrasonographically detectable neonatal brain white matter lesions are the most important identifiable risk factor for cerebral palsy. Inflammatory cytokines released during the course of intrauterine infections have been implicated in the genesis of brain white matter lesions and subsequent cerebral palsy. This study was undertaken to determine whether fetuses who subsequently were diagnosed to have periventricular brain white matter lesions could be identified by determining the concentrations of inflammatory cytokines in the amniotic fluid. STUDY DESIGN: Women with complicated preterm gestations underwent amniocentesis for clinical indications. Amniotic fluid concentrations of tumor necrosis factor-alpha, interleukin-1beta, interleukin-6, and the natural interleukin-1 receptor antagonist were determined by immunoassay. Periventricular white matter lesions of the neonate were diagnosed by neurosonography. Univariate and multivariate analyses were conducted. RESULTS: Ninety-four women and their neonates were included in the study; white matter lesions were diagnosed in 24% (23/94) of the newborns. The mothers of newborns with brain white matter lesions had higher median concentrations of tumor necrosis factor-alpha, interleukin-1beta, and interleukin-6 (but not interleukin-1 receptor antagonist) in amniotic fluid than did those who were delivered of newborns without white matter lesions (p < 0.01 for each). Acute histologic chorioaminionitis was more common in the placentas of neonate with white matter lesions than in those without these lesions (82% [18/22] vs 42% [30/71], p < 0.005). Neonates with white matter lesions were delivered at a lower mean gestational age and birth weight and had a higher rate of significant complications (including respiratory distress syndrome, intraventricular hemorrhage, and infection-related complications) than did those without white matter lesions. The differences in median interleukin-1beta and interleukin-6 levels between these two groups remained significant after adjustment for gestational age and birth weight (interleukin-6: odds ratio 5.7, 95% confidence interval 1.3 to 24.4; interleukin-1beta: odds ratio 4.4, 95% confidence interval 1.1 to 17.0). Of the 94 newborns included in this study, 11 died before age 6 months and eight had cerebral palsy; all eight had white matter lesions and elevated cytokine levels in amniotic fluid. Histologic chorioamnionitis was more common in the placentas of neonates with cerebral palsy than in those without cerebral palsy (86% [6/7] vs 44% [33/75], p < 0.05). CONCLUSIONS: Infants at risk for development of brain white matter lesions can be identified by the concentrations of interleukin-6 and interleukin-1beta in amniotic fluid. Our findings support the hypothesis that inflammatory cytokines released during the course of intrauterine infection play a role in the genesis of brain white matter lesions.

Amniocentesis↗
PubMed1997

Detection of human defensin 5 in reproductive tissues.

OBJECTIVES: This study was undertaken to determine whether tissue-specific defensins are expressed within female reproductive tissues. STUDY DESIGN: Messenger ribonucleic acid from amnion, chorion, endometrium, endocervix, myometrium, placenta, small intestine, peripheral blood lymphocytes, and cervical, endometrial, and trophoblast cell lines was reverse transcribed with a 3'-RACE adapter. 3'-RACE polymerase chain reaction was conducted with an upstream human defensin 5 primer and 3'-RACE adapter primer. Polymerase chain reaction products hybridizing to a human defensin 5 probe were cloned for sequence analysis. Sequence data were compared against a nucleotide sequence database, and secondary structure predictions were made. RESULTS: Chorionic tissue, endocervical tissue, endometrial tissue, and an endometrial cell line all demonstrated a single hybridizing 362 bp polymerase chain reaction product. Sequence analysis of all clones demonstrated near-perfect identity with human defensin 5. CONCLUSIONS: Human endocervix, endometrium, and chorion express defensin 5 at the level of transcription. These findings suggest that a previously unrecognized mechanism of protecting female reproductive tissues against infection, by means of a natural antimicrobial system (defensins), may be present.

Amnion↗
PubMed1997

Gliclazide treatment of streptozotocin diabetic rats restores GLUT4 protein content and basal glucose uptake in skeletal muscle.

This study examined whether the treatment of streptozotocin (STZ)-diabetic rats with gliclazide (5 mg/kg body weight twice daily orally) increases muscle glucose uptake. Rats were treated (group G, n = 10) or untreated (group D, n = 11) for 12 days. Normal rats served as controls (group C, n = 11). At the end of the treatment, both basal and insulin-stimulated glucose uptake by the perfused hindquarters were measured. In gastrocnemious muscles, the protein content of GLUT4 and the insulin binding and tyrosine kinase activity of partially purified solubilized insulin receptors were measured. Group G had a lower mean glycemic value during the treatment period than group D (mean +/- SEM, 17 +/- 0.6 v 19.7 +/- 0.5 mmol/L, P < .05), without differences in serum insulin levels. Basal glucose uptake by the hindquarters was significantly higher in group G versus group D (2.8 +/- 0.3 v 1.3 +/- 0.2 mumol/g/h, P < .05), and was not different versus group C (3.6 +/- 0.2 mumol/g/h). Insulin-stimulated glucose uptake was higher (P < .05) in group C compared with the two groups of diabetic rats. Glucose uptake at 10(-7) mol/L insulin was higher in group G than in group D (9.2 +/- 0.6 v 7.0 +/- 0.6 mumol/g/h, P < .05). Both insulin binding and tyrosine kinase activity were similar in muscle insulin receptors from both groups of diabetic rats. The GLUT4 protein content was higher in group G than in group D (95 +/- 10 v 57 +/- 7 arbitrary units [AU]/microgram protein, P < .05) and similar to that of group C (113 +/- 13 AU/microgram protein). In conclusion, gliclazide has a glucose-lowering effect in STZ-diabetic rats that could be attributed to an increase in muscle glucose clearance by a post-insulin receptor mechanism, probably related to a normalization of GLUT4 content.

Animals↗
PubMed1997

Modification of Christensen urease test as an inexpensive tool for detection of Helicobacter pylori.

About half the world population is infected with Helicobacter pylori. Most live in developing countries where clinical studies face the constraints of high costs of imported rapid diagnostic tests. In this work, we describe and validate a simple local urease test (LUT) to determine the presence of the bacterium in gastric biopsies, and report the incidence of infection among symptomatic patients in Caracas, Venezuela. Statistical comparison of LUT and CLOtest (Delta West, Bentley, Australia) (N = 216 patients) showed that the probability of 95% agreement between the two test was 0.936. Overall incidence of infection determined by the LUT was 65% (N = 229), and it was higher in patients from public (72%; N = 153) than from private (50%; N = 76) hospitals (p = .001). Therefore, the incidence of infection differs in two socioeconomic groups that coexist in the same city. LUT may represent an affordable tool in clinical studies needed to identify social factors that increase the risk of infection by H. pylori.

Adolescent↗
PubMed1997

Pathogenesis of preterm labor and preterm premature rupture of membranes associated with intraamniotic infection.

We have proposed a model in which the initiation of human parturition in the presence of infection is controlled by the host. Systemic maternal infections such as pyelonephritis or localized infections such as deciduitis can trigger parturition by the activation of the monocyte and macrophage system in peripheral blood and human decidua. Preterm labor and preterm PROM can, according to this, be considered events that occur when the intrauterine or maternal environment is hostile and threaten the survival of the fetal-maternal pair. From this point of view, the initiation of preterm labor may have survival value. Why does intrauterine infection result in preterm labor in some cases and PROM in others? It is possible that regulation of different components of the host response has an important role to play in determining clinical presentation. Thus, if preferential activation of the host response leads to the secretion of uterotonic agents (i.e., prostaglandins), preterm labor will result. On the other hand, if the activation of the host response results predominantly in the production of proteases (i.e., leukocyte elastase and MMPs), patients are more likely to experience PROM. Preterm labor and preterm PROM can be considered expressions of the same basic phenomenon: activation of the host-defense macrophage system. Although we have provided evidence that infection is an important factor in the pathogenesis of these conditions, preterm parturition should be considered as a syndrome with multiple causes.

Amnion↗
PubMed1997

The Millard rotation-advancement lip repair using accurate measurements.

For many years a wide variety of surgical techniques for closure of unilateral cleft lip has been used. Still many surgeons prefer the Millard rotation-advancement lip repair because the surgical scar is masked in the filtrum crest and the nostril floor, and it improves the relationship of the alar base of the cleft side, producing harmonious symmetry of the nostril and the nostril sill. In addition, it uses and preserves the lip anatomy, returning lip tissue into its normal position, minimizing the amount of tissue that is discarded, and reconstructing the orbicular oris muscle. One of the major disadvantages of this procedure is the lack of accurate measurements. This article demonstrates that rotation-advancement lip repair can be performed with accurate measurements as in the Tennison-Randall lip repair and tends to invalidate the widely held belief that rotation-advancement lip repair is a "cut as you go" technique.

Cicatrix↗
PubMed1997

Management of thrombotic microangiopathy following allogeneic transplantation: what is the role of plasma exchange?

Thrombotic microangiopathy (TMA) is an infrequent but serious complication of allogeneic transplantation. The success rate of plasma exchange (PE) reported in the treatment of this entity is a controversial subject. We report the outcome of 10 patients with TMA post-allogeneic transplantation after treatment with PE. Two out of the 10 patients have not responded, five had a partial response, but died of acute GVHD or interstitial pneumonitis, and three have responded and recovered. Our study suggests that there are different degrees of TMA severity. Only mild multifactorial cases with no severe hemolysis (LDH activity <1000 U/l) may be fully resolved with PE.

Adolescent↗
PubMed1997

Angiotensin II requires PDGF-BB to induce DNA synthesis in rat mesangial cells cultured in an exogenous insulin-free medium.

BACKGROUND: Mesangial cell proliferation is an important feature of chronic glomerular disease. Different cytokines and vasoactive substances have been implicated in mesangial cell proliferation. However, the role of angiotensin II remains controversial. Furthermore, all the studies made to date have been performed using a medium supplemented with high concentrations of insulin (5 micrograms/ml) in order to facilitate mesangial cell proliferation in vitro. As has recently been reported, insulin causes a change both in extracellular matrix composition and in mesangial cell phenotype, thus mimicking disease conditions. METHODS: We examined the effects of Ang II in synchronized and proliferating mesangial cells with and without growth factor (PDGF-BB, bFGF and/or insulin) supplementation and the effects of exogenous administration of insulin on mesangial proliferation by measuring the bromodeoxyuridine (BrdU) uptake. RESULTS: Angiotensin II itself caused no increase in BrdU incorporation. However, it exerted a significant synergistic effect on PDGF-BB-induced DNA synthesis (P < 0.05) in quiescent medium and tended to stimulate BrdU uptake by proliferating cells (P = 0.09). BrdU incorporation significantly correlated with direct cell count (r = 0.95). PDGF-BB had the maximal stimulatory effect on DNA synthesis both in quiescent and in proliferative culture conditions. The insulin dose (5 micrograms/ml) which has been shown to cause mesangial cell proliferation in vitro, caused an increase in BrdU incorporation by itself in quiescent medium. CONCLUSIONS: We conclude that in an insulin-free medium, mimicking in vivo glomerular conditions, PDGF-BB or proliferative medium are needed to allow Ang II-induced DNA synthesis in mesangial cell culture.

Angiotensin II↗
PubMed1997

Detection of human defensins in the placenta.

PROBLEM: The placenta is a highly selective barrier against the hematogenous dissemination of infectious agents. Despite the presence of seemingly intact physical and immunologic barriers, infections nonetheless occur. These observations prompted the examination of placental tissue, amnion, and chorion for previously unrecognized protective mechanisms. METHOD OF STUDY: Messenger RNA from term placenta, amnion, and chorion were reverse transcribed using a 3' RACE adapter. 3' rapid amplification of cDNA ends (RACE)-polymerase chain reaction (PCR) was conducted on cDNA from these tissues to detect the presence of human defensins. Southern analysis and partial sequence analysis were subsequently performed to confirm identity. RESULTS: PCR amplification of placental, amnion, and chorion cDNA yielded a 468-bp product and a weakly detectable band of 300 bp. Southern analysis demonstrated two corresponding hybridizing bands in the placenta, amnion, and chorion but not from a negative cDNA control. Partial sequence analysis of the 468-bp product from placenta confirmed the presence of either defensin 1 or 3 in human placenta. CONCLUSIONS: The human placenta, amnion, and chorion express defensins at the level of transcription. These findings suggest that a novel and previously unrecognized mechanism of protecting the fetus against infection may be present within these tissues.

Amnion↗
PubMed1997

Selectivity of protoporphyrin IX fluorescence for condylomata after topical application of 5-aminolaevulinic acid: implications for photodynamic treatment.

To examine the potential of using photodynamic therapy (PDT) in condylomata, we studied the distribution and kinetics of protoporphyrin IX (PpIX) formation in condylomata acuminata and adjacent normal skin after topical application of 5-aminolaevulinic acid (ALA). PpIX fluorescence spectra were measured hourly in vivo after ALA application. After gross fluorescence imaging, the lesions were biopsied, and fluorescence microscopy was performed. All three PpIX fluorescence detection modalities suggested selectivity of PpIX formation in condylomata after topical ALA application. In 17 of 25 condylomata, there was significantly greater fluorescence compared with adjacent normal skin. The greatest lesional to normal skin fluorescence ratios occurred after 2 h. The most likely mechanism for increased lesional PpIX formation in condylomata is enhanced stratum corneum permeability. Based on our results, ALA/PDT is a potential field therapy for condylomata. PpIX fluorescence imaging after ALA application may also be useful for localizing condylomata prior to treatment.

Administration, Cutaneous↗
PubMed1996

Sulfonylureas stimulate glucose uptake through GLUT4 transporter translocation in rat skeletal muscle.

We studied the effect of gliclazide on glucose uptake and GLUT4 translocation in skeletal muscle. Rat hindquarters were perfused in the absence or presence of gliclazide (300 micrograms/ml), insulin or both drugs. The basal glucose uptake was increased 2.7-fold by gliclazide (p < 0.05). Gastrocnemius muscles perfused with gliclazide had a significant increase (2.4-fold) in the GLUT4 content in plasma membranes compared to basal conditions (p < 0.05). The stimulations produced by 1 nM insulin on muscle glucose uptake (2.8-fold) and on GLUT4 level in plasma membranes (2.5-fold) were similar to those produced by gliclazide. The effect of insulin on the glucose uptake and on the GLUT 4 translocation was significantly enhanced by gliclazide (3.4-fold and 3.7-fold vs basal, respectively). These data show that sulfonylureas stimulate glucose uptake in skeletal muscle by promoting the movement of GLUT4 to the plasma membrane.

Animals↗
PubMed1996

A central body region defined by a position-specific molecule in the planarian Dugesia (Girardia) tigrina: spatial and temporal variations during regeneration.

We have isolated a monoclonal antibody, TCEN49, that displays position-specific binding to the central body region of the planarian Dugesia (Girardia) tigrina. TCEN49 binds to all cell types of the central area with the exception of epithelial cells. Labeled cells are more related by position than by lineage. In the intact organism, boundaries between labeled and unlabeled regions are very sharp and in a dynamic state as they shift in relative position along the body axis during growth and degrowth. During regeneration, TCEN49 antigen is present in the area which will form the central region before it is morphologically apparent. Moreover, when animals are cut through the central region, TCEN49 label fades quickly from those regions determined to become head or tail well before morphogenesis takes place. Taken together, these data suggest that expression of TCEN49 antigen is very sensitive to positional information changes and that it could be involved in the expression of central-body positional identity. TCEN49 antigen is a glycoprotein with an apparent molecular weight of 4.5 kDa, as determined by gel immunoblotting. Immunogold light and electron microscopy demonstrate that the main location of TCEN49 antigen is intracellular (granular components of secretory cells and, to a lesser extent, clear cytoplasmic vesicles and heterochromatin blocks), though it is also detected in the extracellular matrix. TCEN49 antigen represents the first position-specific molecule reported in planarians to date.

Animals↗
PubMed1996

Impairment of the semantic network in schizophrenia.

It is well established that patients with schizophrenia display a variety of language impairments. Despite considerable research, however, the underlying mechanisms of the language deficits in schizophrenia remain unclear. Representations of semantic networks of 56 patients with schizophrenia and 28 normal comparison (NC) subjects of similar ages and educational levels were generated by multidimensional scaling and Pathfinder analyses of their responses on the Animal Fluency Test. On the basis of traditional scoring techniques (i.e., total number of correct animal names generated in 60 s), all patients performed significantly worse than the NC subjects. More detailed analyses of the underlying semantic networks revealed that performance in the patients varied according to age of onset and subtype of schizophrenia. The semantic network of patients with late-onset schizophrenia (i.e., with onset after age 45) was virtually identical to that of the NC group. In contrast, the semantic network of patients with a younger age of onset was disorganized and differed significantly from that of the NC subjects. Findings demonstrated that patients with nonparanoid subtypes displayed greater disorganization in their semantic networks than patients with a paranoid subtype. Although general fluency impairments (e.g., difficulties in initiation, retrieval, and search mechanisms) may be sensitive to schizophrenia, per se, specific deficits in the structure of semantic knowledge may be associated with certain characteristics of individual patients with schizophrenia, such as an earlier age of onset and nonparanoid subtype.

Adult↗