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Biomedical subjects

R Mora

Publications and source records attributed to R Mora.

At least 19 recordsLinked to original sources
PubMed2000

Pivotal role of anionic phospholipids in determining dynamic behavior of lung surfactant.

Phosphatidylglycerol (PG) and phosphatidylinositol (PI) are anionic phospholipids (APLs) present in lung surfactant of virtually all species studied, although their specific contribution to function is unknown. This study examines how APLs influence surfactant monolayer stability and adsorption under static and dynamic conditions. Interfacial properties of surfactants reconstituted with native phospholipids (PL), and phospholipids devoid of anionic species (DAPL), were characterized by pulsating bubble surfactometry. Measurements were made for PL and DAPL alone; with 3% surfactant proteins B and C (SP-B/C); with SP-B/C and 5% surfactant protein A (SP-A); and with SP-B/C, SP-A, and 8% neutral lipids (NL). Equilibrium and dynamic properties of PL and DAPL were similar. However, whereas (DAPL + SP-B/C) and (DAPL + SP-B/C + SP-A) mixtures were similar to corresponding PL mixtures with respect to gamma(equil), they displayed markedly different dynamic behavior. In particular, the degree of film compression required to reach gamma(min) was significantly increased in DAPL mixtures (80 to 90% area reduction) compared with PL, although both samples reached gamma(min) < 3.0 dynes/cm. The addition of NL to (DAPL + SP-B/C + SP-A) produced an increase in gamma(min) to 15 to 20 dynes/cm during dynamic compression, whereas NL had no significant impact on the behavior of (PL + SP-B/C + SP-A). Purified PG (5% wt/wt) restored nearly normal dynamic properties to (DAPL + SP-B/C + SP-A + NL), whereas phosphatidylcholine (PC) (5% wt/wt) had no beneficial effect. These results suggest that APLs play a critical role in promoting surface film stability during dynamic compression through interactions with nonlipid surfactant components, and prevent destabilization of the surface film by cholesterol and other NL.

Animals↗
PubMed1999

Caveolin-2 localizes to the golgi complex but redistributes to plasma membrane, caveolae, and rafts when co-expressed with caveolin-1.

We have characterized comparatively the subcellular distributions of caveolins-1 and -2, their interactions and their roles in caveolar formation in polarized epithelial cells. In Fischer rat thyroid (FRT) cells, which express low levels of caveolin-2 and no caveolin-1, caveolin-2 localizes exclusively to the Golgi complex but is partially redistributed to the plasma membrane upon co-expression of caveolin-1 by transfection or by adenovirus-mediated transduction. In Madin-Darby canine kidney (MDCK) cells, which constitutively express both caveolin-1 and -2, caveolin-2 localized to both the Golgi complex and to the plasma membrane, where it co-distributed with caveolin-1 in flat patches and in caveolae. In FRT cells, endogenous or overexpressed caveolin-2 did not associate with low density Triton insoluble membranes that floated in sucrose density gradients but was recruited to these membranes when co-expressed together with caveolin-1. In MDCK cells, both caveolin-1 and caveolin-2 associated with low density Triton-insoluble membranes. In FRT cells, transfection of caveolin-1 promoted the assembly of plasma membrane caveolae that localized preferentially (over 99%) to the basolateral surface, like constitutive caveolae of MDCK cells. In contrast, as expected from its intracellular distribution, endogenous or overexpressed caveolin-2 did not promote the assembly of caveolae; rather, it appeared to promote the assembly of intracellular vesicles in the peri-Golgi area. The data reported here demonstrate that caveolin-1 and -2 have different and complementary subcellular localizations and functional properties in polarized epithelial cells and suggest that the two proteins co-operate to carry out specific as yet unknown tasks between the Golgi complex and the cell surface.

Animals↗
PubMed1999

Expression of caveolin-1 is required for the transport of caveolin-2 to the plasma membrane. Retention of caveolin-2 at the level of the golgi complex.

Caveolins-1 and -2 are normally co-expressed, and they form a hetero-oligomeric complex in many cell types. These caveolin hetero-oligomers are thought to represent the assembly units that drive caveolae formation in vivo. However, the functional significance of the interaction between caveolins-1 and -2 remains unknown. Here, we show that caveolin-1 co-expression is required for the transport of caveolin-2 from the Golgi complex to the plasma membrane. We identified a human erythroleukemic cell line, K562, that expresses caveolin-2 but fails to express detectable levels of caveolin-1. This allowed us to stringently assess the effects of recombinant caveolin-1 expression on the behavior of endogenous caveolin-2. We show that expression of caveolin-1 in K562 cells is sufficient to reconstitute the de novo formation of caveolae in these cells. In addition, recombinant expression of caveolin-1 allows caveolin-2 to form high molecular mass oligomers that are targeted to caveolae-enriched membrane fractions. In striking contrast, in the absence of caveolin-1 expression, caveolin-2 forms low molecular mass oligomers that are retained at the level of the Golgi complex. Interestingly, we also show that expression of caveolin-1 in K562 cells dramatically up-regulates the expression of endogenous caveolin-2. Northern blot analysis reveals that caveolin-2 mRNA levels remain constant under these conditions, suggesting that the expression of caveolin-1 stabilizes the caveolin-2 protein. Conversely, transient expression of caveolin-2 in CHO cells is sufficient to up-regulate endogenous caveolin-1 expression. Thus, the formation of a hetero-oligomeric complex between caveolins-1 and -2 stabilizes the caveolin-2 protein product and allows caveolin-2 to be transported from the Golgi complex to the plasma membrane.

Biological Transport↗
PubMed1999

[Mid-latency auditory evoked responses in Alzheimer's disease: evaluation of P1 and P3 waves].

A great deal of research has revealed a frequent association between hearing impairment and Alzheimer's disease. Many of these studies have, however, been criticized for the lack of statistical significance, for the methodology used and for doubts regarding the diagnostic criteria used. The lack of uniform results prompted the present research. On the basis of some works in the literature, the authors felt that the study of middle and long-latency auditory evoked potentials, and their expression characterized by the P1 and P3 waves, the appropriate instrument for exploring the cortical and subcortical tracts of the auditory system which are most compromised in Alzheimer's disease. In fact, numerous studies have suggested that wave P1 is generated by peduncle-pontine nucleus cells of the tegmentum and that wave P3 is generated by sites located in the temporal lobes and hippocampus. The present study was conducted on 15 subjects suffering from Alzheimer's disease and 15 controls. Four subjects were excluded from the study because they were affected by Alzheimer's disease with severe dementia and were, thus, unable to cooperate. The 15 controls underwent accurate clinical and instrumental evaluation to rule out any neurological and intellectual disorders. The results for wave P1 show a statistically significant difference between the subjects affected by Alzheimer's disease and the controls. In fact, there was a difference in the presence of this potential. Moreover there was a statistically significant difference in P1 between those patients with average dementia and the controls but not between those with slight dementia and the controls. Finally, comparison of the abnormalities in P1 potential and P3 latency showed that in Alzheimer's disease alterations in P3 arise earlier and are more constant than alterations in P1. The physiopathological meaning of these results is discussed.

Aged↗
PubMed1998

Caveolin transfection results in caveolae formation but not apical sorting of glycosylphosphatidylinositol (GPI)-anchored proteins in epithelial cells.

Most epithelial cells sort glycosylphosphatidylinositol (GPI)-anchored proteins to the apical surface. The "raft" hypothesis, based on data mainly obtained in the prototype cell line MDCK, postulates that apical sorting depends on the incorporation of apical proteins into cholesterol/glycosphingolipid (GSL) rafts, rich in the cholesterol binding protein caveolin/VIP21, in the Golgi apparatus. Fischer rat thyroid (FRT) cells constitute an ideal model to test this hypothesis, since they missort both endogenous and transfected GPI-anchored proteins to the basolateral plasma membrane and fail to incorporate them into cholesterol/glycosphingolipid clusters. Because FRT cells lack caveolin, a major component of the caveolar coat that has been proposed to have a role in apical sorting of GPI-anchored proteins (Zurzolo, C., W. Van't Hoff, G. van Meer, and E. Rodriguez-Boulan. 1994. EMBO [Eur. Mol. Biol. Organ.] J. 13:42-53.), we carried out experiments to determine whether the lack of caveolin accounted for the sorting/clustering defect of GPI-anchored proteins. We report here that FRT cells lack morphological caveolae, but, upon stable transfection of the caveolin1 gene (cav1), form typical flask-shaped caveolae. However, cav1 expression did not redistribute GPI-anchored proteins to the apical surface, nor promote their inclusion into cholesterol/GSL rafts. Our results demonstrate that the absence of caveolin1 and morphologically identifiable caveolae cannot explain the inability of FRT cells to sort GPI-anchored proteins to the apical domain. Thus, FRT cells may lack additional factors required for apical sorting or for the clustering with GSLs of GPI-anchored proteins, or express factors that inhibit these events. Alternatively, cav1 and caveolae may not be directly involved in these processes.

Animals↗
PubMed1998

[Comparative study of sevoflurane and nitrous oxide versus halothane and nitrous oxide in pediatric anesthesia: efficacy and hemodynamic characteristics during induction].

OBJECTIVES: To study the efficacy, side effects and hemodynamics of anesthetic induction in pediatric patients using sevoflurane and nitrous oxide or halothane and nitrous oxide. PATIENTS AND METHODS: We studied 80 pediatric ASA I-II patients aged between 1 and 10 years old scheduled for infraumbilical surgery of short duration. The patients were randomly assigned to two groups of 40 to receive one of the two drug combinations. All the children were premedicated with nasal midazolam 0.2 mg.kg-1. Induction was by inhalation of increasing concentrations of sevoflurane or halothane. The maximum inspired concentration during induction was 7% for sevoflurane and 3% for halothane. We analyzed induction time, side effects and hemodynamic variables. RESULTS: The induction time was 2.06 +/- 0.5 min for halothane and 1.6 +/- 0.6 min for sevoflurane (p < 0.01). We observed no differences between the groups in coughing, laryngospasm, bronchospasm, secretions, apnea, nausea, vomiting, agitation or hiccoughing. Supraventricular beats appeared in 22.5% of patients in the halothane group and in 5% of the sevoflurane group. Induction with both anesthetics caused significant decreases from baseline blood pressure levels but no significant changes in heart rate. CONCLUSIONS: Inhaled sevoflurane in 60% nitrous oxide provides rapid but gentle anesthetic induction, with hemodynamic stability and a low incidence of airway complications. Sevoflurane is therefore a reasonable alternative to halothane for pediatric surgery.

Anesthesia, Inhalation↗
PubMed1997

Static and dynamic posturography in prevalent laterally directed whiplash injuries.

Static and dynamic posturography was used to study patients who had experienced a prevalent laterally directed whiplash in a car accident. Results of both static and dynamic examinations were recorded. Findings showed that the whiplash injury had provoked shifting of the pressor center of the body toward a side that was at least indicative of the kind of cervical twist experienced, even when not corresponding to the prevalent direction of the trauma incurred.

Adult↗
PubMed1997

Growth factor and cytokine-regulated hyaluronan-binding protein TSG-6 is localized to the injury-induced rat neointima and confers enhanced growth in vascular smooth muscle cells.

Hyaluronan (HA) and HA-binding proteins have been implicated in a diverse array of biological processes, including development, tissue repair, and tumor invasion. However, the role of HA and HA-binding proteins in atherosclerosis and restenosis is poorly understood. PS4 (TSG-6) is a HA-binding protein expressed by cultured vascular smooth muscle cells (SMCs) in response to serum and growth factor stimulation. To delineate a possible role for TSG-6 in vascular disease progression, we have characterized its expression in cultured SMCs and in a rat vascular injury model, and we have studied the effect of constitutive overexpression of TSG-6 on SMC behavior. We found that interleukin-1 (IL-1) but not tumor necrosis factor or interleukin-6 was able to stimulate TSG-6 expression in SMCs. The IL-1 pathway could be distinguished from the growth factor pathway by its insensitivity to protein synthesis inhibitors. Furthermore, epidermal growth factor, fibroblast growth factor-1, and transforming growth factor-beta1 were all capable of augmenting maximum IL-1-induced expression of TSG-6. To gain further insight into the function of TSG-6 in SMCs, we examined the effect of constitutive overexpression of TSG-6 on these cells. We found that TSG-6-overexpressing cells grew >50% faster than control cells. Furthermore, this growth advantage became more evident in the absence of serum growth factors, with an average increase in cell number of 118% over control cells after 6 days. Consistent with these in vitro data, we observed intense immunostaining for TSG-6 in proliferating SMCs in the rat neointima after injury, whereas only an occasional cell was positive for TSG-6 in the medial layer and in nonballooned arteries. We conclude that the expression of TSG-6 is tightly controlled by growth factors and cytokines via two distinct pathways in SMCs and that overexpression of TSG-6 confers a growth advantage to these cells.

Animals↗
PubMed1997

Frontiers in Internal Medicine.

Clinical research in Internal Medicine has provided many scientific advances during the past few years. However, the newly generated information overrides the time available to read all of the medical literature regarding advances in Internal Medicine. The goal of this review is to summarize some of the most relevant improvements in clinical practice published over the last few years. From Cardiology to Pulmonology, the authors of this review expose in a succinct way what they and many of their peers consider to be the most transcendental information gathered from thousands of publications. The authors of this review article have attempted to avoid sensationalism by including facts instead of just simply optimistic preliminary findings that can mislead clinicians' decision making. The review is focused on information obtained through well-designed, prospective clinical trials and cohorts where the effectiveness of medical interventions and diagnostic procedures were tested.

Clinical Trials as Topic↗
PubMed1996

[Optokinetic nystagmus and visual-vestibular interaction in subjects with "whiplash injuries"].

We studied the behaviour of Vestibular Nystagmus (VOR), of Optokinetic Nystagmus (OKN) and of Visuo-Vestibular-Ocular-Reflex (VVOR) in seven normal subjects and in thirty-two patients who had undergone cervical trauma in an automobile accident with the so called "whiplash mechanism". Thirteen subjects underwent examination within the first three months after the accident (first group), six subjects between the third and the sixth months (third group). Ocular movements was recorded according to the usual method by means of a Tonnies electronystagmograph with eight channels. The subjects, head blocked, sat on a Tonnies rotatory chair Pro model which was placed in the middle of a rotatory cylindrical chamber 2 metres in diameter and 1.9 metres in height. The width internal area was covered with thirty-two black vertical contrast. The rotatory cylinder was lighted from above by a 100 W bulb and was driven by a direct current engine which turned it clockwise and counterclockwise up to 200 degrees/sec., maximum speed, with preset acceleration ranging from 1 degree to 2 degrees/sec. All the subjects underwent to Rotatory Vestibular Stimulation by Stop test from a constant angular velocity of 90 degrees/sec. with clockwise and counterclockwise rotation, "stare type" Optokinetic stimulation with a cylinder rotation velocity of 30 degrees/sec. for 60 seconds and to contemporary Rotatory Vestibular and Optokinetic Stimulation (VVOR) so that OKN was VOR counterdirectional. The results of our experience show a statistically significative mean gain decrease of VOR and VVOR nystagmus (beating OKN direction) calculated on the first three beats in the patients of the first group and a significative increase of OKN mean gain in all the patients of the three groups. Furthermore, in sixteen out of thirty-two patients (seven in the first group, two in the second and seven in the third) we observed (during VVOR examination, immediately after stop) a nystagmus beating VOR direction lasting from 3 to 15 seconds.

Adult↗
PubMed1994

Subunit composition of lipoprotein(a) protein.

We determined the molecular weight of four different apo(a) polymorphs by sedimentation equilibrium in 6 M guanidine hydrochloride in order to estimate the molar ratio of apo(a) to apoB in Lp(a). They had molecular weights of 289,000, 310,000, 341,000, and 488,000 and 15, 16, 18, and 27 kringle 4 domains, respectively. Their carbohydrate content was similar (23.2 wt %), as was their partial specific volume (0.682 mL/g). Knowing the mass of apo(a), we estimated the molar ratio of apo(a) to apoB from (1) the molecular weight of the protein moiety of the four respective parent Lp(a) particles as calculated from their mass and percentage composition and the mass of apoB, (2) the mass of apo(a) lost from Lp(a) upon its reduction and carboxymethylation, by determining the difference in mass between Lp(a) and Lp(a-), and (3) from the mass (measured by sedimentation equilibrium in 6 M guanidine hydrochloride) of the lipid-free apoB-apo(a) complex (1.06 x 10(6) daltons) of the Lp(a) particle with the smallest apo(a) polymorph by subtracting the mass of apoB. Our results obtained with each of the three different physicochemical methods indicated that the protein moiety of each of the four Lp(a) particles that was investigated consisted of a complex of two molecules of apo(a) and one molecule of apoB.

Apolipoproteins B↗
PubMed1994

The endothelial cell binding site for advanced glycation end products consists of a complex: an integral membrane protein and a lactoferrin-like polypeptide.

Advanced glycation end products (AGEs), formed as the result of the extended interaction of proteins with ketoses, modulate central properties of endothelial cells and mononuclear phagocytes by interacting with a cell surface binding site comprised of a novel integral membrane protein (receptor for AGE = RAGE) and a lactoferrin-like polypeptide (LF-L), the latter having sequence identity to lactoferrin (LF). To further understand this cellular binding site, the interaction of RAGE with LF-L and LF was characterized. By ligand blotting and a solid state competitive binding assay, 125I-LF-L and 125I-LF bound to RAGE immobilized on nitrocellulose membranes or polypropylene tubes in a time-dependent and reversible manner, demonstrating a high affinity component with Kd approximately 100 pM. The interaction of 125I-LF-L and 125I-LF with RAGE was independent of iron in LF and was competed by addition of an excess of unlabeled carboxyl-terminal portion of LF. Cross-linking studies with purified 125I-LF-L and RAGE, in the presence of disuccinimidyl suberate, showed a new, slowly migrating band, corresponding to a complex of RAGE and LF-L, and cross-linking on mouse aortic endothelial cells showed two new slowly migrating bands on immunoblotting visualized with both anti-RAGE IgG and anti-LF-L IgG. These data lead us to propose that the endothelial cell surface binding site for AGEs consists of LF-L bound noncovalently to RAGE anchored in the cell membrane.

Amino Acid Sequence↗
PubMed1993

In vitro formation of oxidatively-modified and reassembled human low-density lipoproteins: antioxidant effect of albumin.

In early atherogenesis, excess plasma lipoproteins accumulate into the arterial lesion-prone areas as modified and reassembled lipoproteins (MRLp) appearing mostly as lipid droplets and vesicles. In the present study we produced such MRLp, in a cell-free system, devoid of any component of extracellular matrix, by subjecting in vitro human low-density lipoproteins (LDL) to autoxidation or copper-induced oxidation, for up to 96 h. As visualized by negative staining electron microscopy, a large number of lipoprotein particles (Lp) were progressively transformed into aggregates (ALp), fused particles (FLp) and vesicles (VLp). These modifications were paralleled by peroxidation of the samples as revealed by chemical analysis of each MRLp fraction isolated by a three-step purification procedure. LDL peroxidation in the above conditions was inhibited by the presence of albumin as assessed by TBARS and lipid analysis, and by the lack of MRLp formation. This protective effect was independent of albumin source (bovine, human, rabbit) and occurs at an albumin/LDL ratio of 1 when Cu2+ was present, and at a ratio of 0.25 in autoxidative conditions. The results show that: (i) in vitro LDL autoxidation or copper-induced peroxidation in a cell-free system can generate modified and reassembled lipoproteins similar to those detected in vivo in the arterial intima at the inception of atherogenesis; (ii) Lp particles appear to be sequentially transformed in self-aggregates, droplets and vesicles; (iii) serum albumin can completely prevent these LDL alterations.

Antioxidants↗
PubMed1993

Isolation of amaranth flour proteins by fractionation procedures and sonication.

The use of whole and defatted amaranth flour for protein isolation of Osborne fractions is described. Extractability of prolamins, the minor fraction, increased from 2.8 to 5% by adding a reducing agent. Glutelins proved to be poorly solubilized (3.3%) in dilute acetic acid, but they reached a high solubility value (40.8%) using a borate buffer in the presence of a reducing agent and a detergent; solubility remarkably declined without the latter two chemicals. Sonication (a fast and simple technique) in the presence of a detergent proved to be more efficient, compared with stirring, for extractability of total unreduced proteins.

Albumins↗
PubMed1993

Regulation of human mononuclear phagocyte migration by cell surface-binding proteins for advanced glycation end products.

Nonenzymatic glycation of proteins occurs at an accelerated rate in diabetes and can lead to the formation of advanced glycation end products of proteins (AGEs), which bind to mononuclear phagocytes (MPs) and induce chemotaxis. We have isolated two cell surface-associated binding proteins that mediate the interaction of AGEs with bovine endothelial cells. One of these proteins is a new member of the immunoglobulin superfamily of receptors (termed receptor for AGEs or RAGE); and the second is a lactoferrin-like polypeptide (LF-L). Using monospecific antibodies to these two AGE-binding proteins, we detected immunoreactive material on Western blots of detergent extracts from human MPs. Radioligand-binding studies demonstrated that antibody to the binding proteins blocked 125I-AGE-albumin binding and endocytosis by MPs. Chemotaxis of human MPs induced by soluble AGE-albumin was prevented in a dose-dependent manner by intact antibodies raised to the AGE-binding proteins, F(ab')2 fragments of these antibodies and by soluble RAGE. When MP migration in response to N-formyl-Met-Leu-Phe was studied in a chemotaxis chamber with AGE-albumin adsorbed to the upper surface of the chamber membrane, movement of MPs to the lower compartment was decreased because of interaction of the glycated proteins with RAGE and LF-L on the cell surface. The capacity of AGEs to attract and retain MPs was shown by implanting polytetrafluoroethylene (PTFE) mesh impregnated with AGE-albumin into rats: within 4 d a florid mononuclear cell infiltrate was evident in contrast to the lack of a significant cellular response to PTFE with adsorbed native albumin. These data indicate that RAGE and LF-L have a central role in the interaction of AGEs with human mononuclear cells and that AGEs can serve as a nidus to attract MPs in vivo.

Animals↗
PubMed1992

Primitive synovial chondromatosis of the hip joint.

Primitive synovial chondromatosis of the hip is quite rare. Through the presentation of four new cases, the authors discuss the pathologic and clinical features of this disease and evaluate the performance of imaging studies, emphasizing the value of CT scan for confirmation of radiographic findings. The indication for surgical treatment is analyzed for each stage of the disease.

Adult↗