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Biomedical subjects

I Lopez

Publications and source records attributed to I Lopez.

At least 19 recordsLinked to original sources

Evaluation of DNA damage in exfoliated tear duct epithelial cells from individuals exposed to air pollution assessed by single cell gel electrophoresis assay.

The search for relevant target cells for human monitoring purposes has increased during the last few years. Cells such as sperm, buccal or nasal and gastric epithelium are being used. In this study, we report the use of exfoliated tear duct epithelial cells as a potential material for human biomonitoring studies, since these cells are a target for environmental pollutants. We employed the alkaline single cell gel electrophoresis (SCGE) assay to evaluate for differences in the basal level of DNA damage between young adults from the south (exposed mainly to high levels of ozone) and from the north (exposed principally to hydrocarbons) regions of Mexico City. We found an increase in DNA migration in tear duct epithelial cells from individuals who live in the southern part of the city compared to those living in the northern part. Moreover, young people who live in the southwest part of the city with the highest values of ozone presented the highest values of DNA damage. These results show the feasibility of using exfoliated tear duct epithelial cells in human biomonitoring studies.

Adolescent↗

Unbiased stereological quantification of neurons in the human vestibular ganglion.

Vestibular ganglion (VG) neurons are bipolar neurons that relay peripheral vestibular information to the CNS. Neuron counts in normal humans provide a basis for quantitative studies on the effects of aging or pathological conditions in the audiovestibular systems. No prior study has employed unbiased stereological technique to count human VG neurons. This study used unbiased stereology in the form of the optical fractionator to estimate the total number of human VG neurons in archival temporal bone specimens. An average (+/- s.d.) of 27330+/-2593 neurons was found in specimens from five patients with no history of vestibular pathology. This result, a significant departure from results of past studies, provides the first unbiased baseline value to compare with future stereologically based studies on the human VG.

Adolescent↗

Metabolic bone disease in IBD.

A substantial number of patients with inflammatory bowel disease (IBD) will manifest extra-intestinal complications. Metabolic bone disease and arthropathies are among the most debilitating of these. Decreased bone mineral density and increased fracture risk may occur in relation to the underlying disease itself or result from vitamin, mineral, and hormonal deficiencies; medications used to treat the underlying disease; lifestyle; and perhaps other factors. In many cases, the factors remain unidentified. Options for the treating clinician include correction of these deficiencies, treatment of the underlying disease, and use of medication to promote bone formation and decrease bone resorption.

Arthritis↗

Subcellular immunolocalization of NMDA receptor subunit NR-1 in the chinchilla vestibular periphery.

The immunohistochemical localization of N-methyl-D-aspartate (NMDA) glutamate receptor subunit, NR-1 was investigated in the chinchilla cristae ampullaris and utricular maculae at the light and electron microscopy level with the use of specific antipeptide antibodies. The afferent calyces that innervate type I hair cell, and the basolateral type I vestibular hair cell is NR-1 immunoreactive. The afferent boutons innervating type II hair cells and the basal portion of type II hair cell are NR-1 non-immunoreactive. These findings are consistent with NMDA receptor mediation of afferent excitatory neurotransmission from type I, but not type II hair cells to the primary afferent vestibular nerve. The NMDA receptors on the type I hair cell are located in areas of synaptic specialization, and may play a role in autoregulation. The localization of the NMDA receptor subunit in type I but not type II hair cells is intriguing.

Animals↗

Expression of BDNF and TrkB mRNAs in the crista neurosensory epithelium and vestibular ganglia following ototoxic damage.

Following ototoxic lesion with the aminoglycoside gentamicin, the vestibular neurosensory epithelia undergo degeneration and then limited spontaneous regeneration. The spatio-temporal expression of brain-derived neurotrophic factor (BDNF) and of its high affinity receptor (trkB) mRNA was investigated in the vestibular end organs and ganglia of chinchillas following gentamicin ototoxicity. In the vestibular ganglia of untreated chinchillas, the level of expression of BDNF mRNA is low. At 1 and 2 weeks after intraotic treatment with gentamicin, BDNF mRNA levels in the vestibular ganglia were elevated significantly compared to untreated chinchillas and chinchillas 4 weeks after treatment. At 4 weeks after gentamicin treatment, BDNF mRNA levels were at intact levels of expression. In the crista ampullaris, high levels of BDNF transcripts were found in the untreated chinchillas. At 1 and 2 weeks after treatment, when only supporting cells are present in the crista, BDNF mRNA was undetectable. Four weeks after aminoglycoside treatment BDNF mRNA was present in the epithelium but at lower levels than in the intact epithelium. In contrast to its ligand, high levels of trkB mRNA hybridization were present in the vestibular ganglia of untreated chinchillas and trkB mRNA levels did not change following gentamicin treatment. In the vestibular epithelia, trkB mRNA was not detected either in the intact epithelium or after gentamicin ototoxicity. These data suggest that BDNF may be involved in the maintenance of the vestibular ganglia and contribute to neurite outgrowth to new and repaired hair cells following ototoxic damage.

Animals↗

Selective activation of phospholipase D2 by unsaturated fatty acid.

Although oleate has been implicated in the regulation of phospholipase D (PLD) activity, the molecular identity of the oleate-stimulated PLD is still poorly understood. We now report that oleate selectively stimulates the enzymatic activity of PLD2 but not of PLD1, with an optimal concentration of 20 microM in vitro. Intriguingly, phosphatidylinositol 4,5-bisphosphate (PIP2) synergistically stimulates the oleate-dependent PLD2 activity with an optimal concentration of 2.5 microM. These results provide the first evidence that oleate is a PLD2-specific activating factor and PLD2 activity is synergistically stimulated by oleate and PIP2.

Dose-Response Relationship, Drug↗

Internal auditory artery infarction: clinicopathologic correlation.

OBJECTIVE: To study the pathophysiology of labyrinthine infarction. BACKGROUND: The syndrome of sudden onset vertigo or hearing loss is commonly attributed to inner ear vascular disease, yet histologic studies of isolated labyrinthine infarction in humans have been rare and have not included a complete examination of the vertebrobasilar vascular system. METHODS: Temporal bones, brainstem, cerebellum, and the supplying blood vessels were subjected to gross and microscopic postmortem examinations in a 92-year-old woman who had a sudden onset of vertigo and hearing loss in the right ear 7 years before death. RESULTS: There were prominent atherosclerotic changes at the vertebrobasilar junction, but the internal auditory artery and its branches were patent on both sides. Histologic studies showed degenerative changes in the cochlea and vestibular labyrinth on the right. The posterior canal ampulla and saccular macule were relatively preserved showing partial areas of intact sensory epithelium with underlying nerve fibers. The right vestibulocochlear nerve showed a fibrotic scar and multiple patchy areas of degeneration. These findings are most consistent with a transient period of reduced perfusion of the internal auditory artery. CONCLUSION: The partial sparing of the inferior vestibular labyrinth may indicate a decreased vulnerability to ischemia because of its better collateral blood supply.

Aged↗

Mortality according to age and burned body surface in the Virgen del Rocio University Hospital.

The application of updated clinical protocols for the treatment of burned patients is showing very good results. The mortality curves according to age and the percentage of burned body surface could be of great use for the comparison of clinical results between different burns units. The probability of survival in 1000 consecutive patients admitted to the Burns Unit of the Virgen del Rocio University Hospital between July, 1993 and August, 1997, is compared, by graphic analysis, with the mortality curves of other centers, obtaining similar results. We conclude that the results of medical attendance in our unit are in line with those considered as a reference.

Adolescent↗

Reflux gastritis in gastroesophageal reflux disease: A histopathological study.

Increased intragastric alkaline reflux has been documented in patients with reflux esophagitis; however, the effect on gastric histology has not been investigated in this population. We examined gastric biopsies from 72 non-acid-suppressed patients with gastroesophageal reflux disease (GERD) for changes of reflux gastritis or other forms of gastritis. In the Helicobacter pylori-negative GERD patients (n = 52) using the Dixon scoring system for reflux gastritis with a threshold score of >/=11, reflux gastritis was found in 15% (three of 20) of GERD patients with erosions and in no GERD patients without erosions. When the reflux gastropathy threshold score was changed to more than 8, 90% (18 of 20) of GERD patients with erosions and 19% (six of 32) of GERD patients without erosions were classified as having reflux gastritis. Regardless of the reflux gastritis threshold used, only 14% (seven of 52) of the H pylori-negative GERD patients exhibited normal gastric histology. Inactive chronic gastritis or nonspecific reactive changes were histologic findings in those gastric biopsies not classified as reflux gastritis or normal. All H pylori-positive GERD patients (n = 20) had active chronic gastritis. We conclude that most GERD patients will exhibit some form of gastric pathology: either reflux gastritis, chronic gastritis, or nonspecific reactive changes, depending on what reflux threshold score is applied and the presence of H pylori. Studies to define the intragastric alkaline content in conjunction with gastric histopathology need to be performed to further define those reflux esophagitis patients with reflux gastritis.

Adult↗

Glutamate-like immunoreactivity during hair cell recovery after gentamicin exposure in the chinchilla vestibular sensory periphery.

OBJECTIVE: Determine the expression of glutamate by immunohistochemistry in normal and recovering vestibular hair cells in the chinchilla crista ampullaris after gentamicin ototoxicity. STUDY DESIGN: In five groups of three animals each, ototoxicity was produced by placing gentamicin (50 microg)-impregnated Gelfoam pellets within the perilymphatic space of the superior semicircular canal. Animals were sacrificed at 1, 2, 4, 8, and 16 weeks after treatment. A group of normal (n=3) animals was also processed. METHODS: For the detection of glutamate the inner ears of these animals were dissected, and the horizontal cristae ampullaris embedded in plastic. Two-micron-thick tissue sections were obtained and incubated with monoclonal antibodies against glutamate. The immunoreaction was detected using the avidinbiotinylated-complex technique and diaminobenzidine was the chromogen. RESULTS: Normal sensory epithelia demonstrated type I and type II hair cells with moderate glutamate-like immunoreactivity. Supporting cells demonstrated no glutamate-like immunoreactivity. Afferent nerve fibers and calyxes surrounding type I hair cells demonstrated strong glutamate-like immunoreactivity. At 1 and 2 weeks after treatment the few type II hair cells surviving ototoxic treatment (15%-18%) contained moderate glutamate-like immunoreactivity, supporting cells showed no immunoreactivity, and nerve terminals and fibers displayed strong immunoreactivity. At 4 and 8 weeks after treatment, recovered hair cells (80%) had greater glutamate-like immunoreactivity when compared with normal hair cells, supporting cells displayed no glutamate-like immunoreactivity, and afferent fibers contained strong glutamate-like immunoreactivity. At 16 weeks, glutamate-like immunoreactivity in hair cells returned to normal level. CONCLUSION: Glutamate may be used as an indicator of hair cell differentiation and as an index of the molecular recovery of hair cells after ototoxicity.

Animals↗

Effect of phosphate on parathyroid hormone secretion in vivo.

Alterations in phosphate homeostasis play an important role in the development of secondary hyperparathyroidism in renal failure. Until recently, it was accepted that phosphate retention only increased parathyroid hormone (PTH) secretion through indirect mechanisms affecting calcium regulation and calcitriol synthesis. However, recent in vitro studies have suggested that phosphate may directly affect PTH secretion. Our goal was to determine whether in vivo an intravenous phosphate infusion stimulated PTH secretion in the absence of changes in serum calcium. Three different doses of phosphate were infused intravenously during 120 minutes to increase the serum phosphate concentration in dogs. Sulfate was also infused intravenously as a separate experimental control. A simultaneous calcium clamp was performed to maintain a normal ionized calcium concentration throughout all studies. At the lowest dose of infused phosphate (1.2 mmol/kg), serum phosphate values increased to approximately 3 mM, but PTH values did not increase. At higher doses of infused phosphate (1.6 mmol/kg and 2.4 mmol/kg), the increase in serum phosphate to values of approximately 4 mM and 5 mM, respectively, was associated with increases in PTH, even though the ionized calcium concentration did not change. Increases in PTH were not observed until 30-60 minutes into the study. These increases were not sustained, since by 120 minutes PTH values were not different from baseline or controls despite the maintenance of marked hyperphosphatemia. During the sulfate infusion, serum sulfate values increased by approximately 3-fold, but no change in PTH values were observed. In conclusion, an acute elevation in serum phosphate stimulated PTH secretion in the intact animal, but the magnitude of hyperphosphatemia exceeded the physiologic range. Future studies are needed to determine whether PTH stimulation is more sensitive to phosphate loading in states of chronic phosphate retention. Moreover, the mechanisms responsible for the delay in PTH stimulation and the failure to sustain the increased PTH secretion need further evaluation.

Animals↗

The protective effect of brain-derived neurotrophic factor after gentamicin ototoxicity.

HYPOTHESIS: Brain-derived neurotrophic factor (BDNF) influences the process of hair cell recovery in the vestibular sensory epithelium of the chinchilla after local application of gentamicin (GM). BACKGROUND: Hair cell regeneration in the inner ear after GM ototoxicity has been demonstrated. However, the mechanisms responsible for this recovery have yet to be completely elucidated. This report examines the protective and proliferative effects that BDNF exerts on vestibular hair cells in experiments designed to further elucidate the mechanisms of hair cell regeneration. METHODS: The inner ears of three separate groups of chinchillas were treated with GM only, GM and BDNF simultaneously, and GM followed by BDNF 1 week later. The numbers of hair and supporting cells in the horizontal cristae of each group were then estimated at 1, 2, 4, and 8 weeks, and the data were compared. RESULTS: Type I hair cells after GM treatment completely disappeared. After simultaneous BDNF and GM treatment, their numbers decreased to 23% at 1 week and progressively disappeared by week 8. When BDNF was applied 1 week after GM administration, type I hair cells recovered to 12% at week 4 and 28% at week 8. Type II hair cells after GM treatment decreased to 15%, but recovered to 83% 4 weeks later. Simultaneous administration of BDNF and GM prevented the ototoxic effects of GM alone. When BDNF was administered 1 week after GM, type II hair cell recovery was accelerated and was greater than after GM alone (81% versus 18%). Supporting cells after GM treatment decreased to 74% at 1 week after treatment, recovered to 91% at 2 weeks, and remained at 86% at 4 weeks and 85% at 8 weeks. With the simultaneous administration of BDNF and GM, supporting cells significantly decreased at 2 weeks after treatment (63%), but recovered to normal by week 8. CONCLUSIONS: These results suggest that BDNF provided simultaneously with GM minimizes the ototoxic effect of GM on type II hair cells. The increase in the number of new hair cells when BDNF is provided after ototoxic damage is evidence of the proliferative capacity of this neurotrophic factor.

Animals↗

Gastric histologic findings in patients with nonsteroidal anti-inflammatory drug-associated gastric ulcer.

The purpose of this study was to characterize gastric histologic findings in patients with nonsteroidal anti-inflammatory drug (NSAID)-associated gastric ulcer (GU). Gastric biopsy specimens from 136 patients with NSAID-related GU were compared with those from a control population of 185 patients with Helicobacter pylori-related gastritis. Foveolar hyperplasia, edema, muscular stranding, vascular ectasia, and active and chronic inflammation were semiquantitatively graded. Lymphoid aggregates, intestinal metaplasia, atrophy, and cystic gland changes were noted. No single parameter reliably distinguished between the two populations, although moderate/severe foveolar hyperplasia, edema, and vascular ectasia were significantly more common in the NSAID group. With use of the Dixon scoring system for reflux/reactive gastropathy, with a threshold score of 11 or more, 39 (29%) patients in the NSAID group were correctly diagnosed as having reactive gastropathy (sensitivity, 29%; specificity, 100%; positive predictive value, 100%). When the Dixon scoring threshold score was decreased to 8 or more, 114 (84%) patients were classified as having reactive gastropathy (sensitivity, 84%; specificity, > 99%; positive predictive value, > 99%). We conclude that a decreased threshold enhances the usefulness of the reactive gastropathy score in the NSAID-related GU population. Additional studies, however, must be performed to evaluate the effect of a lowered threshold relative to a normal population and those with other causes of reactive gastropathy.

Adult↗

[Massive benign pleural schwannoma].

Schwannoma is a neoplasm of the peripheral nerve sheath that develops from schwann's cells. Pleural involvement is uncommon, and typically originates from an intercostal nerve of the posterior-superior mediastinum to then extend along the parietal and mediastinal pleura. We report a case of benign schwannoma of the right hemithorax, which we believe to be the largest ever reported at this time. The clinical presentation, acute respiratory failure, was unusual. The imaging findings of this tumor are described.

Aged↗

Cloning and initial characterization of a human phospholipase D2 (hPLD2). ADP-ribosylation factor regulates hPLD2.

Phospholipase D (PLD) has been implicated in a variety of cellular processes including vesicular transport, the respiratory burst, and mitogenesis. PLD1, first cloned from human, is activated by small GTPases such as ADP-ribosylation factor (ARF) and RhoA. Rodent PLD2, which is approximately 50% identical to PLD1 has recently been cloned from mouse embryo (Colley, W., Sung, T., Roll, R., Jenco, J., Hammond, S., Altshuller, Y., Bar-Sagi, D., Morris, A., and Frohman, M. (1997) Curr. Biol. 7, 191-201) and rat brain (Kodaki, T., and Yamashita, S. (1997) J. Biol. Chem. 272, 11408-11413). We describe herein the cloning from a B cell library and expression of human PLD2 (hPLD2). The open reading frame is predicted to encode a 933-amino acid protein (Mr of 105,995); this corresponds to the size of the protein expressed in insect cells using recombinant baculovirus. The deduced amino acid sequence shows 53 and 90% identity to hPLD1 and rodent PLD2, respectively. The mRNA for PLD2 was widely distributed in various tissues including peripheral blood leukocytes, and the distribution was distinctly different from that of hPLD1. hPLD1 and hPLD2 both showed a requirement for phosphatidylinositol 4,5-bisphosphate. Both isoforms showed optimal activity at 10-20 mol % phosphatidylcholine in a mixed lipid vesicle system and showed comparable basal activities in the presence of phosphatidylinositol 4,5-bisphosphate. Unexpectedly, ARF-1 stimulated the activity of hPLD2 expressed in insect cells about 2-fold, compared with a 20-fold stimulation of hPLD1 activity. Thus, not only PLD1 but also hPLD2 activity can be positively regulated by both phosphatidylinositol 4,5-bisphosphate and ARF.

ADP-Ribosylation Factors↗

Umbilical blood flow and neonatal morphometry: a multivariate analysis.

OBJECTIVE: To study the relation between the state of umbilical blood flow and neonatal morphometry. STUDY DESIGN: We have recorded data from 460 pregnant women. Umbilical systolic to diastolic ratio was measured within the 3 days prior to the birth. Weight, height, head and chest circumferences, ponderal and head to chest circumferences ratio were considered for the study. RESULTS: In a univariate analysis, the best correlated variable to S/D ratio was the weight (r=-0.35). However, a forward stepwise multiple regression analysis demonstrated that the best predictors of S/D ratio were height and ponderal index. Small-for-gestational-age fetuses with placental insufficiency (n=20) had a significant more pronounced decrease of weight, height, head circumference and chest circumference than those with normal placental perfusion (n=31). The degree of decrease of ponderal index and HC/TC was similar in both groups. CONCLUSIONS: Umbilical blood flow is one important factor determining newborn morphometry. If only one growth variable is considered, the best correlation with umbilical S/D ratio is found to be the weight. The multivariate regression analysis concluded that the two most influential factors by umbilical blood flow are height and ponderal index and the rest of the morphometric parameters lost their significant correlations when adjusted by these variables. The impairment on neonatal morphometry in small-for-gestational-age fetuses associated to placental insufficiency is more severe than that with normal placental perfusion. However, it does not have a more pronounced decrease of ponderal index than the rest of causes of small-for-gestational-age fetuses.

Adult↗

Hair cell formation in cultures of dissociated cells from the vestibular sensory epithelium of the bullfrog.

HYPOTHESIS: Bullfrog vestibular hair cells are capable of regenerating in vitro. BACKGROUND: Recent studies have established that sensory organs in the inner ear of vertebrates continue to produce hair cells after birth. However, the mechanisms responsible for the regulation of this process are not well understood. The current study reports the development of a novel method for the culture of dispersed cells from the bullfrog inner ear. METHODS: New hair cell formation in this in vitro preparation was shown by sequential photomicroscopy. Studies with the selective marker for mitotic activity 5-bromo-2-deoxyuridine (BrdU) were done to estimate the level of cell proliferation and to quantify postmitotic hair cell formation. Finally, confirmation of cell type was obtained by scanning electron microscopy and by the use of specific markers for hair cells. RESULTS: Once the optimal culture conditions were established in the initial experiments, the formation of new hair cells was directly visualized in all unstained live cultures and fixed preparations without exception. Asymmetric division of progenitor cells, with subsequent differentiation of one of the daughter cells into new hair cells, also was documented by photomicroscopy. Approximately 12% of the cells were labeled with BrdU, of which 6% were hair cells, showing that new hair cell formation was subsequent to mitotic division in vitro. The identity of newly formed hair cells was verified as follows: 1) morphologically by scanning electron microscopy; 2) by positive labeling with phalloidin-rhodamine, a marker for actin; and 3) by positive calmodulin immunocytochemistry. CONCLUSIONS: This study reports the development of an in vitro culture preparation in which undifferentiated epithelial cells proliferate to become new hair cells. Evidence is provided of division of hair cell progenitors and subsequent differentiation of the daughter cells as one of the mechanisms involved in new hair cell formation in the culture preparation. This newly developed cell culture technique provides a powerful tool for further study of the process of hair cell formation in the vestibular end organ.

Animals↗

Expression of the AMPA-selective receptor subunits in the vestibular nuclei of the chinchilla.

The distribution of the AMPA type glutamate receptor has been investigated throughout the central nervous system; however, no detailed description of its distribution is available in the vestibular nuclei. In the present study, in situ hybridization histochemistry and immunohistochemistry were used to localize the messenger RNAs and proteins of the AMPA-selective receptor subunits GluR1, GluR2, GluR3 and GluR4 in the vestibular nuclei of the chinchilla. Immunohistochemistry with subunits specific antisera showed differential distribution of the subunits in the vestibular nuclei. GluR2/3 antiserum labeled the most neurons, suggesting that many if not all vestibular neurons receive glutamatergic input. GluR1-positive neurons were fewer than GluR2/3 immunoreactive neurons and GluR4 immunoreactivity was found in the fewest number of neurons. GluR1 and GluR4 immunoreactivity was also found in astrocyte-like structures. In situ hybridization with 35S-labeled complementary RNA probes confirmed the distribution of the AMPA receptor subunits obtained by immunohistochemistry. Quantitative analysis of the levels of hybridization showed a high degree of diversity in the levels of expression of the GluR2 subunit mRNA, with the highest levels of expression in the giant Deiter's cells of the lateral vestibular nuclei and the lowest levels in the small neurons throughout the vestibular nuclei. The subunit compositions of the AMPA receptors determine their physiological properties. Differential distribution and levels of expression of the receptor subunits in the vestibular nuclei may be related to the characteristics of information processing through the vestibular system.

Animals↗