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Biomedical subjects

R Fernandez

Publications and source records attributed to R Fernandez.

At least 37 records · Page 2Linked to original sources
PubMed2001

New sesquiterpene derivatives from the red alga Laurencia scoparia. Isolation, structure determination, and anthelmintic activity.

Eleven sesquiterpenes (1-11) and one long chain aldehyde (12) have been isolated from the dichloromethane extract of the red alga Laurencia scoparia. Four of them are new natural products. Scopariol (1) is a new natural product with an unusual rearranged chamigrane-type structure. The other three are beta-chamigrenes: isorigidol (2), (+)-3-(Z)-bromomethylidene-10 beta-bromo-beta-chamigrene (3), and (-)-3-(E)-bromomethylidene-10 beta-bromo-beta-chamigrene (4). The in vitro activity of compounds 1-12 against the parasitant stage of Nippostrongylus brasiliensis (L4) has been studied.

Animals↗
PubMed2001

Amino acid levels and ratios in serum and cerebrospinal fluid of patients with optic neuropathy in Cuba.

Twenty-one amino acids were determined in serum and cerebrospinal fluid of 12 patients with endemic, and in the cerebrospinal fluid of 22 patients with epidemic optic neuropathy. For the endemic patients, there was a decrease in aspartate and taurine in the serum with respect to controls. The ratios aspartate/taurine and taurine/valine were decreased, and glutamate/taurine was increased in the serum. Some of the altered amino acid ratios indicate preponderance of excitatory to inhibitory molecules. The ratio with valine corresponded to the decrease in taurine and the maintenance of valine concentration, an amino acid related to anthropometric parameters. A typical malnutrition pattern was not observed, as the levels of essential amino acids were not significantly modified. In the cerebrospinal fluid there were increases in aspartate, glutamate and threonine, the first two probably indicating a neurodegenerative disorder or some type of metabolic alteration, primary or secondary to the disease. The increase in threonine could be related to lipid metabolism, but it is not clear at present. A wide variety of amino acid ratios were increased in the cerebrospinal fluid of patients with endemic optic neuropathy, mainly pointing to an excitatory condition and some metabolic alterations. In the cerebrospinal fluid of patients with epidemic optic neuropathy there was an increase in aspartate and glutamate, and increase in glutamate/taurine, glutamate/glycine, and gamma-aminobutyric acid/glycine ratios. Interesting differences were also observed between patients from different periods of time, but with the same clinical features, and the modifications of amino acid concentrations in the cerebrospinal fluid, such as glutamine, threonine and tryptophan. The present results indicate a disorder in the metabolism of amino acids, support a specific deficit, especially for taurine, an imbalance between excitatory and inhibitory amino acids, and a possible relation to viral infections.

Adult↗
PubMed2001

Increased adhesiveness and internalization of Neisseria gonorrhoeae and changes in the expression of epithelial gonococcal receptors in the Fallopian tube of copper T and Norplant users.

Interaction of Neisseria gonorrhoeae with the oviductal epithelium in vitro was examined in 2 cm length segments obtained after surgical sterilization from users of copper T intrauterine device (IUD) or Norplant and control women. Segments perfused with N.gonorrhoeae suspensions were incubated from 30 min up to 4 h, fixed, frozen and cut in 6--10 microm sections. Bacteria were detected immunohistochemically with rabbit anti-gonococcal serum followed by light and confocal microscopy. Adhesion and internalization of gonococci by epithelial cells were observed at all incubation times, and both were higher in explants from users of copper T IUD or Norplant implants than controls. The epithelium of controls expressed CD66 and syndecan-1; but CD46 was found in only one out of six cases. The epithelium of copper T IUD users expressed CD66 but not syndecan-1 or CD46. Users of Norplant exhibited expression of CD46, CD66 and syndecan-1. Label was always found along the luminal border of the epithelium. There were more intraepithelial lymphocytes in users of contraceptive methods than in controls. Results indicate that (i) N.gonorrhoeae invade the oviductal epithelium from the first minutes of exposure, (ii) the epithelium is constitutively endowed with two known receptors for the gonococcus, CD66 and syndecan-1, (iii) copper T IUD and Norplant users exhibit higher rates of attachment and internalization of the gonococcus into the oviductal epithelium associated with changes in expression of gonococcal receptors.

Adult↗
PubMed2001

PAF receptor and PAF acetylhydrolase expression in the endosalpinx of the human Fallopian tube: possible role of embryo-derived PAF in the control of embryo transport to the uterus.

BACKGROUND: Prostaglandin-E(2) and platelet-activating factor (PAF) are embryonic-derived signals that time embryo passage into the uterus in the mare and hamster respectively. PAF-like activity is detectable in the spent media of preimplantation human embryos and it has been suggested that PAF may be the embryonic signal that controls embryo transport to the uterus in our species. The actions of PAF are regulated at the level of its synthesis and degradation as well as the expression of a specific cell surface receptor (PAFr). The enzyme PAF acetylhydrolase (PAF-AH) degrades PAF. This study was undertaken to examine whether or not PAFr and PAF-AH are expressed in the human Fallopian tube and to identify the cell types in which they are expressed. METHODS: The presence of PAFr mRNA in tissue extracts was investigated using reverse transcription-polymerase chain reaction. We amplified the predicted amplicon for PAFr mRNA from RNA samples extracted from Fallopian tubes. The expression of PAF-AH was detected by Western blot and the localization of PAFr and PAF-AH proteins was detected by immunohistochemistry. RESULTS: Utilizing antibodies against PAFr and PAF-AH, co-localization of the two proteins in the epithelium and stromal cells were demonstrated. CONCLUSIONS: These observations show that the human Fallopian tube expresses PAFr and PAF-AH at a location compatible with the proposed paracrine role of early embryo-derived PAF.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed2001

Exposure to perflubron is associated with decreased Syk phosphorylation in human neutrophils.

Liquid ventilation with perflubron is associated with reduced neutrophil recruitment into the lung during acute injury. Perflubron also reduces chemotactic responses, the respiratory burst, and cytokine production in neutrophils and in alveolar macrophages in vitro. In the current studies, the effect of perflubron on neutrophil chemotaxis to formyl-Met-Leu-Phe (fMLP) and phagocytosis of opsonized sheep erythrocytes (EA) correlated with decreased phosphorylation of Syk, an important intracellular second messenger in pathways regulating neutrophil functional responses. Brief (5 min) exposure of neutrophils to perflubron resulted in a dose-dependent reduction in chemotaxis to fMLP and reduced phagocytosis of EA but no apparent morphological changes as seen by electron microscopy. Concurrently, there was a reduction in both total cytosolic tyrosine phosphorylation and Syk phosphorylation. Binding studies indicated that this effect was neither a result of impaired ligand-receptor affinity nor a change in the number of fMLP receptors available on the neutrophil surface. These results suggest that perflubron nonspecifically affects cellular activation as measured by tyrosine phosphorylation perhaps by interfering with transmembrane signal transduction.

Binding Sites↗
PubMed2001

Effect of malaria on soluble transferrin receptor levels in Tanzanian infants.

The diagnosis of iron deficiency anemia in malaria endemic areas is complicated by the influence of the infection on the laboratory tests conventionally used to assess iron status. Determination of soluble transferrin receptor (sTfR) levels has been shown to be a sensitive indicator of iron deficiency in adults and is not affected by a range of infectious and inflammatory conditions. The utility of sTfR levels in the diagnosis of iron deficiency in malaria endemic areas remains unresolved. Three hundred and fourteen infants in a rural area of southern Tanzania living under conditions of intense and perennial malaria transmission were studied to determine the utility of sTfR plasma levels in the assessment of iron deficiency anemia. Independent of the presence of anemia, malaria parasitemia was associated with a significant increase in sTfR plasma levels that were even higher than those found in iron deficiency anemia. We conclude that the measurement of sTfR levels does not have a role in the diagnosis of iron deficiency anemia in young children exposed to malaria infection.

Anemia, Iron-Deficiency↗
PubMed2001

Bimanual haptic workstation for laparoscopic surgery simulation.

Realistic laparoscopic surgical simulators will require real-time graphic imaging and tactile feedback. Our research objective is to develop a cost-effective haptic workstation for the simulation of laparoscopic procedures for training and treatment planning. The physical station consists of a custom-built frame into which laparoscopic trocars and surgical tools may be attached/inserted and which are continuously adjustable to various positions and orientations to simulate multiple laparoscopic surgical approaches. Instruments inserted through the trocars are attached to end effectors of two haptic devices and interfaced to a high speed PC with fast graphics capability. The haptic device transduces 3D motion of the two manually operated surgical instruments into slave maneuvers in virtual space. The slave instrument tips probe the simulated organ. Simulations currently in progress include: 1) Surface-only renderings, deformation, and haptic interactions with elements in the gall gladder surgical field; 2) Voxel-based simulations of the bulk manipulation of tissue; 3) laparoscopic herniorrhaphy. This system provides force feed-forward from the grasped tools to the contact tissue in virtual space, with deformation of the tissue by the virtual probe, and force feedback from the deformed tissue to the operator's hands.

Computer Graphics↗
PubMed2000

Stress-induced activation of c-Jun N-terminal kinase in sensory ganglion neurons: accumulation in nuclear domains enriched in splicing factors and distribution in perichromatin fibrils.

In response to cellular stress, the activation of the JNK cascade mediates phosphorylation of c-Jun that promotes its transactivation, which in turn activates the transcription of specific genes. In an experimental model of neuronal stress in vivo, by means of immunofluorescence and kinase assays we have found a reversible activation of JNK induced by the administration of the anti-cancer drug Adriamycin. In control neurons, a considerable basal level of the active, phosphorylated JNK was detected in neuronal nuclei, with a speckled distribution in addition to a diffuse nucleoplasmic signal. Adriamycin-induced neuronal stress was associated with a notable increase of this nuclear immunostaining, indicating activation of the JNK pathway which was confirmed by the increase of JNK enzymatic activity, while no changes in the total JNK were detected by Western blots. The JNK neuronal response to stress was also accompanied by an increase in the nuclear immunoreactivity for c-Jun and also by the de novo appearance of a strong nuclear phospho-c-Jun signal. These effects tend to revert to the control situation after 24 h of Adriamycin treatment. The nuclear compartmentalization of phospho-JNK and its substrate c-Jun was analyzed by confocal laser microscopy. Phospho-JNK strongly colocalizes with snRNPs in nuclear speckles, while the former was not concentrated in the coiled bodies. Upon stress induction, both c-Jun and phospho-c-Jun show a nucleoplasmic distribution in euchromatin domains, with the nucleoli free of immunolabeling. Furthermore, the nuclear speckles enriched in phospho-JNK exhibit a very low or undetectable signal with both c-Jun antibodies. Immunogold electron microscopy confirms the accumulation of phospho-JNK in interchromatin granule clusters (nuclear speckles), while in the nucleoplasm this kinase is mainly localized in perichromatin fibrils. Both c-Jun and phospho-c-Jun were also detected in perichromatin fibrils. Double labeling experiments show the colocalization of phospho-JNK and phospho-c-Jun in certain perichromatin fibrils. These results indicate that the neuronal response to the Adriamycin-induced stress is mediated by the activation of the JNK pathway. The accumulation of phospho-JNK in nuclear speckles raises the possibility that this kinase may be involved in the phosphorylation of an unknown splicing factor. Moreover, the colocalization of phospho-JNK and c-Jun in perichromatin fibrils, which are associated with sites of active transcription, suggests that these nuclear structures may be putative sites for the phosphorylation of JNK substrates.

Animals↗
PubMed2000

The Drosophila shark tyrosine kinase is required for embryonic dorsal closure.

Dorsal closure (DC) in the Drosophila embryo requires the coordinated interaction of two different functional domains of the epidermal cell layer-the leading edge (LE) and the lateral epidermis. In response to activation of a conserved c-Jun amino-terminal kinase (JNK) signaling module, the dorsal-most layer of cells, which constitute the LE of the stretching epithelial sheet, secrete Dpp, a member of the TGFbeta superfamily. Dpp and other LE cell-derived signaling molecules stimulate the bilateral dorsal elongation of cells of the dorsolateral epidermis over the underlaying amnioserosa and the eventual fusion of their LEs along the dorsal midline. We have found that flies bearing a Shark tyrosine kinase gene mutation, shark(1), exhibit a DC-defective phenotype. Dpp fails to be expressed in shark(1) mutant LE cells. Consistent with these observations, epidermal-specific reconstitution of shark function or overexpression of an activated form of c-Jun in the shark(1) mutant background, rescues the DC defect. Thus, Shark regulates the JNK signaling pathway leading to Dpp expression in LE cells. Furthermore, constitutive activation of the Dpp pathway throughout the epidermis fails to rescue the shark(1) DC defect, suggesting that Shark may function in additional pathways in the LE and/or lateral epithelium.

Animals↗
PubMed2000

Formation of intranuclear crystalloids and proliferation of the smooth endoplasmic reticulum in schwann cells induced by tellurium treatment: association with overexpression of HMG CoA reductase and HMG CoA synthase mRNA.

Administration of tellurium (Te) in weaning rats causes a well-established demyelinating neuropathy induced by the inhibition in myelinating Schwann cells (SC) of the synthesis of cholesterol, a major component of the myelin sheath, at the level of squalene epoxidase. We have used this experimental model of Te neuropathy to study the biogenesis and reorganization of the endomembranes of the nuclear envelope and endoplasmic reticulum (ER) in response to Te treatment by ultrastructural analysis and in situ hybridization for the detection of HMG CoA reductase and synthase mRNA, which encode key enzymes in cholesterol synthesis. The adaptive response of myelinating SC to cholesterol depletion includes cell hypertrophy, the formation of tubular invaginations of proliferating nuclear membranes giving rise to peculiar nuclear inclusions termed crystalloids, and, at the cytoplasmic level, the formation of lamellar bodies of rough ER, proliferation of the smooth ER, and overexpression of HMG CoA reductase and synthase mRNAs. The changes revert after withdrawal of Te treatment. Our results show that the biogenesis and structural organization of both endomembrane systems change dynamically upon Te-induced cholesterol depletion, indicating that this constituent plays a critical role in the organization of nuclear envelope and ER compartments in SC. The results also suggest that the HMG CoA reductase, an integral membrane protein of ER, provides the signal for the extensive membrane assembly. While the physiological meaning of crystalloid remains to be clarified, the hypertrophy of the smooth ER may represent a cytoprotective mechanism involved in detoxification of the neurotoxic agent or its metabolic derivates.

Animals↗
PubMed2000

MR imaging findings in granular cell tumor of the neurohypophysis: a difficult preoperative diagnosis.

Granular cell tumor is a rare neoplasm arising within the neurohypophysis. We describe the MR imaging findings in two symptomatic patients. In one patient with history of panhypopituitarism, MR images showed a large sellar and suprasellar mass. The other patient presented with acute loss of vision in her left eye, and MR images showed a suprasellar mass with compression of the optic chiasm.

Female↗
PubMed2000

Na+-independent proton secretion in MDCK-C11 cells.

In this work we studied the proton secretion mechanisms in recently cloned MDCK-C11 cells. We measured intracellular pH (pHi) in monolayers grown on permeable filters, using the pH-sensitive probe BCECF and an inverted epifluorescence microscope. The cells have a basal pHi of 7.20+/-0.01 (n=136) and after an acid-releasing NH4Cl pulse pHi recovered at a rate (dpHi/dt) of 0.167+/-0.006 pH units/ per minute (n=20). This rate decreased significantly when Na+ was removed from both cell surfaces, and was further reduced when they were both perfused with a solution containing no Na+ and K+. pHi recovery fell again in the presence of concanamycin (at a concentration of 4.6x10(-8) M; a specific inhibitor of the vacuolar H+-ATPase). When Na+ was removed from the apical or the basolateral side, pHi recovery (in pH units per minute) was significantly reduced to 0.099+/-0.008 (n=11) and 0.086+/-0.01 (n=10), respectively. The Na+-independent mechanism of pHi recovery was significantly inhibited by the presence of 5 x 10(-5) M Schering 28080 (an inhibitor of the H+-K+-ATPase) at the apical side (0.065+/-0.01 versus 0.099+/-0.008 pH units per minute, P<0.05), but not at the basolateral side (0.072+/-0.01 versus 0.086+/-0.01 pH units per minute). On the other hand, concanamycin inhibited the Na+-independent pHi recovery when applied apically (0.0304+/-0.005 pH units per minute, n=7) and basolaterally (0.025+/-0.004 pH units per minute, n=7). From these results we conclude that monolayers of MDCK-C11 cells have a Na+/H+ exchanger and a concanamycin-sensitive H+-ATPase on their apical and basolateral membranes; and a K+-dependent, Schering 28080-sensitive H+-K+-ATPase on their apical side.

Ammonium Chloride↗
PubMed2000

Vector competence of Peruvian mosquitoes (Diptera: Culicidae) for epizootic and enzootic strains of Venezuelan equine encephalomyelitis virus.

Mosquitoes collected in the Amazon Basin, near Iquitos, Peru, were evaluated for their susceptibility to epizootic (IAB and IC) and enzootic (ID and IE) strains of Venezuelan equine encephalomyelitis (VEE) virus. After feeding on hamsters with a viremia of approximately 10(8) plaque-forming units of virus per milliliter, Culex (Melanoconion) gnomatus Sallum, Huchings, & Ferreira, Culex (Melanoconion) vomerifer Komp, and Aedes fulvus (Wiedemann) were highly susceptible to infection with all four subtypes of VEE virus (infection rates > or = 87%). Likewise, Psorophora albigenu (Peryassu) and a combination of Mansonia indubitans Dyar & Shannon and Mansonia titillans (Walker) were moderately susceptible to all four strains of VEE virus (infection rates > or = 50%). Although Psorophora cingulata (Fabricius) and Coquillettidia venezuelensis (Theobald) were susceptible to infection with each of the VEE strains, these two species were not efficient transmitters of any of the VEE strains, even after intrathoracic inoculation, indicating the presence of a salivary gland barrier in these species. In contrast to the other species tested, both Culex (Melanoconion) pedroi Sirivanakarn & Belkin and Culex (Culex) coronator Dyar & Knab were nearly refractory to each of the strains of VEE virus tested. Although many of the mosquito species found in this region were competent laboratory vectors of VEE virus, additional studies on biting behavior, mosquito population densities, and vertebrate reservoir hosts of VEE virus are needed to incriminate the principal vector species.

Animals↗
PubMed1999

A new mutation in the regulatory domain of the myophosphorylase gene affecting protein dimer contact.

We have identified a novel missense mutation in the myophosphorylase gene in a Spanish patient with McArdle's disease. The patient was homozygous for a T-to-C transition at codon 115 (L115P) in exon 3, which changed an encoded leucine (CUG) to a proline (CCG). This is the first mutation to be described in exon 3 and in a protein domain related to dimer contact. These data further emphasize the importance of private mutations in McArdle's disease, some of which are associated with specific ethnic groups.

Glycogen Phosphorylase, Muscle Form↗
PubMed1999

Calorie restriction modulates Th-1 and Th-2 cytokine-induced immunoglobulin secretion in young and old C57BL/6 cultured submandibular glands.

Immunoglobulin production by the salivary gland plays an important role in oral and upper respiratory tract immunity. Age and/or disease may compromise salivary gland function. In order to gain insight into the role of calorie restriction (CR) on immunoglobulin (Ig) production, we determined the effect of ad libitum (AL) feeding and CR in young (3 months) and old (18-24 months) C57BL/6 mouse submandibular glands (SM). The SM tissues were fragmented and cultured in the absence (control) or presence of either Th-1 cytokines, such as interleukin-2 (IL-2) and interferon-gamma (IFN-gamma), or Th-2 cytokines, e.g. IL-4 and IL-5, for seven days. Culture supernatants were then analyzed for immunoglobulin A (IgA), IgM, and IgG2a levels by ELISA. Aging increased basal (control) IgA and IgM production by 3.1-and 3.7-fold, respectively, in AL mice. CR prevented the age-dependent rise of both IgA and IgM, maintaining levels equal to those of young AL mice. Interestingly, age resulted in a decrease of Th-1 cytokine-induced IgA and IgM, and increased IgG2a secretion in AL mice, while Th-2 cytokines did not appear to have an age effect. In general, CR suppressed Ig production induced by both Th-1 and Th-2 cytokines in young mice. In contrast, CR in old mice resulted in enhanced IgA and IgM production to levels similar to those in their young counterparts, while IgG2a was predominantly suppressed by Th-1 and not Th-2 cytokines. The data presented herein show, for the first time, the ability of CR to offset age-induced changes in submandibular gland Ig production, which may play a role in maintaining mucosal immune function, including proper oral health.

Aging↗