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Biomedical subjects

I Lopez

Publications and source records attributed to I Lopez.

At least 19 recordsLinked to original sources
PubMed2007

The calcimimetic R-568 increases vitamin D receptor expression in rat parathyroid glands.

We previously demonstrated that extracellular calcium regulates vitamin D receptor (VDR) expression by parathyroid cells. Since the calcimimetic R-568 potentiates the effects of calcium on the calcium-sensing receptor, it was hypothesized that administration of R-568 may result in increased VDR expression in parathyroid tissue. In vitro studies of the effect of R-568 on VDR mRNA and protein were conducted in cultures of whole rat parathyroid glands and human hyperplastic parathyroid glands. In vivo studies in Wistar rats examined the effect of R-568 and calcitriol alone and in combination. Incubation of rat parathyroid glands in vitro with R-568 (0.001-1 microM) resulted in a dose-dependent decrease in parathyroid hormone (PTH) secretion and an increase in VDR expression (mean +/- SE). Incubation in 1 mM calcium + 0.001 microM R-568 elicited an increase in VDR mRNA (306 +/- 46%) similar to the maximum increase detected with 1.5 mM calcium (330 +/- 42%). In vivo, VDR mRNA was increased after administration of R-568 (168 +/- 9%, P < 0.001 vs. control) or calcitriol (198 +/- 16%, P < 0.001 vs. control). Treatment with R-568 also increased VDR protein in normal rat parathyroid glands and in human parathyroid glands with diffuse, but not nodular, hyperplasia. In conclusion, the present study shows that the calcimimetic R-568 exerts a stimulatory effect on VDR expression in the parathyroid glands of study models and provides additional evidence for the use of calcimimetics in the treatment of secondary hyperparathyroidism.

Aniline Compounds↗
PubMed2006

The elucidation of novel SH2 binding sites on PLD2.

Our laboratory has recently reported that the enzyme phospholipase D2 (PLD2) exists as a ternary complex with PTP1b and the growth factor receptor bound protein 2 (Grb2). Here, we establish the mechanistic underpinnings of the PLD2/Grb2 association. We have identified residues Y(169) and Y(179) in the PLD2 protein as being essential for the Grb2 interaction. We present evidence indicating that Y(169) and Y(179) are located within two consensus sites in PLD2 that mediate an SH2 interaction with Grb2. This was demonstrated with an SH2-deficient GSTGrb2 R86K mutant that failed to pull-down PLD2 in vitro. In order to elucidate the functions of the two neighboring tyrosines, we created a new class of deletion and point mutants in PLD2. Phenylalanine replacement of Y(169) (PLD2 Y169F) or Y(179) (PLD2 Y179F) reduced Grb2 binding while simultaneous mutation completely abolished it. The role of the two binding sites on PLD2 was found to be functionally nonequivalent: Y(169) serves to modulate the activity of the enzyme, whereas Y(179) regulates total tyrosine phosphorylation of the protein. Interestingly, binding of Grb2 to PLD2 occurs irrespectively of lipase activity, since Grb2 binds to catalytically inactive PLD2 mutants. Finally, PLD2 residues Y(169) and Y(179) are necessary for the recruitment of Sos, but only overexpression of the PLD2 Y179F mutant resulted in increased Ras activity, p44/42(Erk) phosphorylation and enhanced DNA synthesis. Since Y(169) remains able to modulate enzyme activity and is capable of binding to Grb2 in the PLD2 Y179F mutant, we propose that Y(169) is kept under negative regulation by Y(179). When this is released, Y(169) mediates cellular proliferation through the Ras/MAPK pathway.

Amino Acid Sequence↗
PubMed2005

The influence of anticoagulants on the measurement of total protein concentration in equine peritoneal fluid.

The aim of this study was to evaluate the influence of two commonly used anticoagulants (K3EDTA and lithium heparin) on refractometric and spectrophotometric measurement of total protein (TP) concentration in equine peritoneal fluid samples. The influence of a commercial solution of K3EDTA, a solution of K3EDTA in distilled water and lithium heparin on the refractometric and spectrophotometric (biuret) quantification of TP content in peritoneal fluid samples was assessed. Total protein concentration measured by refractometry was consistently overestimated in samples with commercial K3EDTA. The solution of K3EDTA in distilled water only caused TP overestimation at high K3EDTA concentrations (>5 micromol/ml). By contrast, lithium heparin did not influence the refractometric values of TP. Neither anticoagulant modified TP values when measured by the biuret method. In conclusion, the use of K3EDTA as anticoagulant may result in a significant overestimation of TP values of peritoneal fluid samples measured by refractometry.

Animals↗
PubMed2005

The influence of the progression of secondary hyperparathyroidism on the set point of the parathyroid hormone-calcium curve.

The influence of secondary hyperparathyroidism (2 HPT) on the set point of the parathyroid hormone (PTH)-Ca(2+) curve is controversial. In vitro experiments have shown an increase in the set point. However, clinical studies with hemodialysis patients have provided a variety of results (increases, decreases and no changes in the set point have been reported). The present study was designed to investigate the influence of the progression of 2 HPT on the set point of the PTH-Ca(2+) curve. The PTH-Ca(2+) curve and the expression of parathyroid calcium receptor (CaR mRNA) and vitamin D receptor (VDR mRNA) have been studied in normal rabbits (group I, n=9) and in nephrectomized rabbits (group II, n=18) at two stages after inducing 2 HPT: 2-3 weeks (group IIA) and 5-6 weeks (group IIB). In group I, the set point of the PTH-Ca(2+) curve was 1.63+/-0.03 mM. A progressive hypocalcemia was detected during the evolution of 2 HPT (groups IIA and IIB). Rabbits from group IIA had a significant (P<0.001) decrease in the set point to values of 1.45+/-0.02 mM. However, the set point increased significantly in group IIB (P<0.001) to 1.56+/-0.03 mM. CaR mRNA was similarly decreased in groups IIA (39+/-12%) and IIB (48+/-7%). No changes were detected in VDR mRNA. In conclusion, a reduction in the set point of the PTH-Ca(2+) curve in response to decreased extracellular Ca(2+) was detected in the early phases of 2 HPT. However, with the progression of 2 HPT the set point tended to increase even though extracellular Ca(2+) was markedly decreased. The increase in the set point in the course of 2 HPT seems to be a complex process that cannot be fully explained by changes in parathyroid CaR mRNA or VDR mRNA.

Animals↗
PubMed2004

Temporal bone histopathology in dominantly inherited audiovestibular syndrome.

OBJECTIVE: To describe the clinical and pathologic features of a new dominantly inherited audiovestibular syndrome. METHODS: History, examination, and audiometric testing in the proband, brother, and son; quantitative rotational testing in the proband and son; histopathology of the cochlea and vestibular labyrinth in the proband; sequencing candidate genes COCH and MYO7A in the brother and son. RESULTS: Affected family members developed slowly progressive hearing loss beginning in their late 30s and progressive imbalance in their early 70s. Three of four affected had brief (minutes) episodes of vertigo typically occurring a few times per year. Auditory and vestibular function testing documented a slowly progressive loss of auditory and vestibular function. Postmortem examination showed a loss of hair cells in the cochlea and vestibular receptor organs. There were no cellular infiltrates or acidophilic deposits. No mutations were found in the COCH or MYO7A genes. CONCLUSIONS: This dominantly inherited audiovestibular syndrome results in a selective loss of hair cells in the auditory and vestibular end organs. Finding the causative gene could have important implications for understanding the pathophysiology of presbycusis and dysequilibrium of aging.

Adult↗
PubMed2004

Superior gluteal nerve: safe area in hip surgery.

Injuries to the superior gluteal nerve are very bad complications in hip surgery. An exact knowledge of its course may be helpful in avoiding such problems. Nineteen half pelvises from ten male and female adult cadavers were dissected. Dissections revealed that the nerve divided into two (89.48%) or three (10.52%) branches after leaving the pelvis. The more caudal branch was responsible for innervation of tensor fascia latae. The distance and the angle from the entry points of all branches of the superior gluteal nerve into the deep surface of the gluteus medium and minimus muscles to the mid-point of the superior border of the greater trochanter were measured. The branch that innerved the tensor fascia latae was also followed. These data were subjected to several statistical tests. Based on these findings, and in order to prevent nerve damage, we propose to define a 2-3 cm safe area above the great trochanter.

Adult↗
PubMed2004

Evaluation of the impact of information about treatment-related risks in patients receiving blood-derived or recombinant medications.

The aims of the study were to evaluate the impact of a written information about treatment related risks in patient receiving blood derived or recombinant medications. Haemophiliac patients and patients with constitutional or acquired immune deficiencies are concerned by this treatment and these information. Our objectives are to evaluate the efficacy of the written information, the knowledge of the patients about these medications and the psychological, emotional impact if these information. The study is based on questionnaires which specified how the patient treat bleeding episodes, their knowledge about viral safety of blood products, the patient's perception of his or her health status and relationship with the physician. Psychological and emotional status are evaluated with the Hospital Anxiety and Depression Scale. The results show the difficulty to inform patients: if the information generate only limited anxiety in patients with haemophilia or immune deficiencies, we observe that the delivery of a written information got a mediocre effect on overall knowledge. We think that this information must be appropriate for patients and be communicated orally within the patient-physician relationship.

Anxiety↗
PubMed2002

Extended preservation of non-heart-beating donor livers with normothermic machine perfusion.

BACKGROUND: Non-heart-beating donor (NHBD) livers represent an important organ pool, but are seldom utilized clinically and require rapid retrieval and implantation. Experimental work with oxygenated perfusion during preservation has shown promising results by recovering function in these livers. This study compared sanguinous perfusion with cold storage for extended preservation of the NHBD liver in a porcine model. METHODS: Porcine livers were subjected to 60 min of in vivo total warm ischaemia before flushing, after which they were preserved by one of two methods: group 1 (n = 4), University of Wisconsin (UW) solution by standard cold storage for 24 h; group 2 (n = 4), oxygenated autologous blood perfusion on an extracorporeal circuit for 24 h. All livers were subsequently tested on the circuit during a 24-h reperfusion phase. RESULTS: Livers in group 1 showed no evidence of viability during the reperfusion phase with no bile production or glucose utilization; they also displayed massive necrosis. Livers in group 2 demonstrated recovery of function by synthetic function, substrate utilization and perfusion haemodynamics; these livers displayed less cellular injury by hepatocellular enzymes. All differences in parameters between the two groups were statistically significant (P < 0.05). These findings were supported by histological examination. CONCLUSION: Warm ischaemia for 1 h and simple cold storage (UW solution) for 24 h renders the liver non-viable. Oxygenated, sanguinous perfusion as a method of preservation recovers liver function to a viable level after 24 h of preservation.

Animals↗
PubMed2002

The influence of acute and chronic hypercalcemia on the parathyroid hormone response to hypocalcemia in rabbits.

OBJECTIVE: To investigate the influence of acute and chronic hypercalcemia on the parathyroid hormone (PTH) response to hypocalcemia. DESIGN: The PTH response to hypocalcemia has been evaluated in three groups of rabbits: Group I, normal rabbits, Group II, normal rabbits subjected to an acute hypercalcemic clamp (induced by CaCl(2) infusion) and Group III, rabbits with chronic hypercalcemia (due to surgical reduction of renal mass). RESULTS: In Group I (baseline Ca(2+)=1.69+/-0.02 mM), hypocalcemia resulted in stimulation of PTH secretion which reached a maximum (PTHmax) of 91.7+/-6.4 pg/ml. In rabbits from Group II, which also had normal baseline Ca(2+) (1.70+/-0.02 mM), plasma Ca(2+) was maintained at an elevated level for 2 h, at around 2.05 mM. The PTH response to hypocalcemia in Group II was attenuated and the PTHmax in these rabbits was 45.6+/-7.4 pg/ml. In rabbits from Group III, baseline Ca(2+) was elevated (2.06+/-0.06 mM) for 1 month. The PTH response to hypocalcemia in Group III was esentially the same as in Group I and PTHmax reached levels of 94.8+/-9.9 pg/ml. CONCLUSIONS: A difference in PTH response to hypocalcemia has been found in rabbits after exposure to either acute or chronic hypercalcemia. After acute hypercalcemia, an attenuated PTH response to hypocalcemia has been identified. Chronic hypercalcemia, however, did not influence the PTH response to hypocalcemia.

Acute Disease↗
PubMed2001

Thrombopoietin stimulates cortactin translocation to the cytoskeleton independently of tyrosine phosphorylation.

Cortactin is an F-actin-binding protein expressed in platelets. During aggregation by thrombin, cortactin associates with Src, is tyrosine phosphorylated, and then translocates to the cytoskeleton. It is also found to associate with Syk during platelet shape change. Since cortactin undergoes tyrosine phosphorylation in platelets activated by thrombopoietin (TPO) that exhibit neither shape change nor aggregation, we investigated whether it could also relocalize to the detergent-insoluble fraction. We demonstrate that cortactin was present as a tyrosine-phosphorylated protein and co-localized with Syk in the Triton X-100-insoluble fraction of TPO-activated platelets. TPO stimulated Syk activation and association with cortactin. Conversely, cortactin associated with the kinases, Syk and Src. Cortactin tyrosine phosphorylation was blocked by Syk kinase inhibitor, piceatannol or Src family kinase inhibitor, PP2, suggesting that it depends on these two kinases. However, piceatannol or PP2 did not prevent cortactin translocation to the detergent-insoluble fraction. These data suggest that tyrosine phosphorylation is not required for cortactin translocation to the detergent-insoluble compartment. Furthermore, TPO activates, through its receptor c-Mpl, a signalling pathway to the cytoskeleton.

Blood Platelets↗
PubMed2001

Unbiased stereological quantification of neurons in the human spiral ganglion.

We applied an unbiased stereological technique, the optical fractionator, on five human archival temporal bone specimens to estimate the total number of spiral ganglion neurons. Available archival human temporal bone specimen has been serially sectioned at 20 microm and every tenth section was stained. All the stained sections passing through the spiral ganglion were used for the analysis. From each section sampled, the counting areas were systematically randomly sampled within the sectional area of the spiral ganglion. The neurons within the counting areas sampled were counted with the optical disector technique. The total number of the human spiral ganglion neurons was estimated by multiplying the number of neurons counted by the reciprocal of the aggregate sampling fraction. We found an average of 41700 neurons with a coefficient of variation of 0.14, which is a significant departure from the previously published data obtained with the assumption-based methods. The mean coefficient of error for the stereological estimates of the total number of human spiral ganglion neurons was 0.078. The present report presents unbiased stereological sampling and counting strategies for the future quantitative studies on the spiral ganglion neurons. The result of the present study provides the first unbiased baseline value of the human spiral ganglion neurons.

Adult↗
PubMed2001

Age-related change in the number of neurons in the human vestibular ganglion.

Dysequilibrium of aging in humans has been speculated to arise from progressive deterioration within anatomical components of the vestibular system. An integral part of this system is vestibular ganglions, which are bipolar neurons that relay peripheral vestibular information to the central nervous system. To assess the effect of aging on the number of human vestibular ganglion neurons, assumption-free stereology in the form of the optical fractionator was used on 20 serially sectioned archival human temporal bone specimens. Donors had no history of vestibular pathology and ranged in age from 2 to 88 years. An average of 25,812 (coefficient of variation = 0.13) vestibular ganglion neurons was found throughout this age range, a significant departure from the results of past studies. Logistics-based regression analysis pointed to a nonlinear pattern of decline in the neuronal population: the number of cells remained roughly constant at about 28,952 cells in youth and then declined gradually between 30 and 60 years of age before leveling off at approximately 23,349 cells in older individuals. This study confirmed the existence of an age-related decline in the primary neurons of the human vestibular system, thus providing one anatomical basis for the increased incidence of imbalance seen with age.

Adolescent↗
PubMed2001

Morphoea in three siblings.

Atrophoderma of Pasini and Pierini (APP) is an uncommon form of localized morphoea that occurs as superficial, hyperpigmented plaques distributed mainly on the trunk and proximal part of the limbs. There is little information about the influence of genetic and environmental factors on disease susceptibility and expression for localized scleroderma, although APP familial cases have been reported. We report three siblings without a family history of autoimmune disease presenting cutaneous lesions suggesting morphoea (APP variant).

Adult↗
PubMed2001

Brain volume changes on longitudinal magnetic resonance imaging in normal older people.

BACKGROUND AND PURPOSE: The purpose of this study is to investigate the longitudinal age-related changes in human brain volume using stereological methods. METHODS: Sixty-six older participants (34 men, 32 women, age [mean +/- SD] 78.9 +/- 3.3 years, range 74-87 years) with normal baseline and follow-up examinations underwent 2 MRIs (magnetic resonance imaging) of the brain on average 4.4 years apart. The volumes of the cerebrum (defined as cortex, basal ganglia, thalamus, and white matter), lateral ventricles, and cerebellum were estimated on the 2 MRIs using an unbiased stereological method (Cavalieri principle). RESULTS: The annual decrease (mean +/- SD) of the cerebral volume was 2.1% +/- 1.6% (P < .001). The average volume of the lateral ventricles on the second MRI was increased by 5.6% +/- 3.6% per year (P < .001). The average volume of the cerebellum on the second MRI was decreased by 1.2% +/- 2.2% per year (P < .001). Even though the average cerebral volume was significantly different between men and women on initial MRI and second MRI, the percentage change of the age-related cerebral volume decrease in male and female brains between initial MRI and second MRI were identical. CONCLUSIONS: The findings showed that there was age-related atrophy of cerebrum and cerebellum and age-related disproportional enlargement of lateral ventricles in normal older men and women.

Aged↗
PubMed2000

A novel bifunctional phospholipase c that is regulated by Galpha 12 and stimulates the Ras/mitogen-activated protein kinase pathway.

Three families of phospholipase C (PI-PLCbeta, gamma, and delta) are known to catalyze the hydrolysis of polyphosphoinositides such as phosphatidylinositol 4,5-bisphosphate (PIP(2)) to generate the second messengers inositol 1,4,5 trisphosphate and diacylglycerol, leading to a cascade of intracellular responses that result in cell growth, cell differentiation, and gene expression. Here we describe the founding member of a novel, structurally distinct fourth family of PI-PLC. PLCepsilon not only contains conserved catalytic (X and Y) and regulatory domains (C2) common to other eukaryotic PLCs, but also contains two Ras-associating (RA) domains and a Ras guanine nucleotide exchange factor (RasGEF) motif. PLCepsilon hydrolyzes PIP(2), and this activity is stimulated selectively by a constitutively active form of the heterotrimeric G protein Galpha(12). PLCepsilon and a mutant (H1144L) incapable of hydrolyzing phosphoinositides promote formation of GTP-Ras. Thus PLCepsilon is a RasGEF. PLCepsilon, the mutant H1144L, and the isolated GEF domain activate the mitogen-activated protein kinase pathway in a manner dependent on Ras but independent of PIP(2) hydrolysis. Our findings demonstrate that PLCepsilon is a novel bifunctional enzyme that is regulated by the heterotrimeric G protein Galpha(12) and activates the small G protein Ras/mitogen-activated protein kinase signaling pathway.

Amino Acid Sequence↗
PubMed2000

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↗