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Biomedical subjects

M Rodriguez

Publications and source records attributed to M Rodriguez.

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

Investigation of Alzheimer's disease-related pathology in community dwelling older subjects who committed suicide.

BACKGROUND: Older people have a higher risk of completed suicide than any other age group worldwide. The contribution of neurodegenerative disease to this risk remains controversial. AIMS: To investigate prevalence of Alzheimer's disease-related (AD) pathology in older suicide victims. METHODS: Ratings of AD pathology using Braak and CERAD protocols were compared in 143 community-dwelling suicide victims aged 65 years or more and 59 motor vehicle accident victims autopsied at the request of an Australian Coroner's Court. RESULTS: There were no significant differences in plaque score or neurofibrillary tangle staging between suicide and control groups. None of the subjects with a history of dementia had neuropathologically confirmed AD. CONCLUSIONS: Our study is the second and largest investigation of the prevalence of AD neuropathology in the elderly suicide population. Unlike the previous study, we did not find an increased prevalence of AD neuropathology despite a history of dementia in 6.3%, implicating other pathologies such as Lewy Body or Vascular dementia in the aetiology of dementia in elderly suicide victims.

Accidents, Traffic↗
PubMed2006

Potential scope of action of tissue kallikreins in CNS immune-mediated disease.

The objective of this study was to define the potential scope of action of tissue kallikreins in T cell-mediated disease of the CNS. We demonstrate quantitatively the differential expression of all 15 human tissue kallikreins within brain, spinal cord and immune compartments. In human Jurkat T cells we demonstrate differential regulation of select kallikreins by CD3 receptor, Concanavilin A (Con A), interleukin 2 (IL2), and lipopolysaccharide (LPS)-mediated activation and by exposure to steroid hormones, dexamethasone, norgestrel, androstan and estradiol. The patterns of co-expression and co-regulation described point to novel effector roles for select tissue kallikreins in neurological disorders involving T cells, such as multiple sclerosis.

Bone Marrow↗
PubMed2006

Analysis of cyclin B1 and CDK activity during apoptosis induced by camptothecin treatment.

We have studied the role of cyclins and cyclin-dependent kinase (CDK) activity in apoptosis induced by camptothecin (CPT). In this model, 22% of the cells stain for annexin-V at 24 h and then proceed to be 93% positive by 72 h. This time window permits the analysis of cyclins in cells that are committed to apoptosis but not yet dead. We provide evidence that cyclin protein levels and then associated kinase levels increase after CPT treatment. Strikingly, cyclin B1 and cyclin E1 proteins are present at the same time in CPT treated HT29 cells. Although cyclin B1 and E1 CDK complexes are activated in CPT treated cells, only the cyclin B1 complex is required for apoptosis since reduction of cyclin B1 by RNAi or roscovitine treatment reduces the number of annexin-V-stained cells. We have detected poorly organized chromosomes and phosphorylated histone H3 epitopes at the time of maximum cyclin B1/CDK kinase activity in CPT-treated cells, which suggests that these cells enter a mitotic catastrophe. Understanding which CDKs are required for apoptosis may allow us to better adapt CDK inhibitors for use as anti-cancer compounds.

Antineoplastic Agents, Phytogenic↗
PubMed2006

Increased neurofibrillary tangles in the brains of older pedestrians killed in traffic accidents.

BACKGROUND/AIMS: Older people are over-represented in pedestrian fatalities, and it has been suggested that the presence of cognitive impairment or dementia in these individuals may contribute to their accidents. Using neuropathological methods, we aimed to compare the prevalence of dementia pathology in fatally injured older pedestrians with similarly aged ambulatory subjects who died from other causes. METHODS: The brains of 52 pedestrians (65-93 years) and 52 controls (65-92 years) were assessed for neurofibrillary tangles (NFT), neuritic plaques, Lewy bodies and vascular lesions using established neuropathological criteria. RESULTS: The examination for Alzheimer's disease (AD) pathology showed that 43% of the pedestrians had NFT scores of III-VI using Braak and Braak staging, compared with 23% of the controls (p < 0.05, Fisher's exact test), indicating incipient, possible or probable AD. There were no differences in the prevalence of pathology for vascular dementia or dementia with Lewy bodies. CONCLUSION: These results suggest that cognitive decline associated with AD, even in the earliest stages of the disease, may be a factor in fatal traffic accidents for older pedestrians. Special measures for pedestrian safety are necessary in areas with high densities of older citizens and especially for those diagnosed as having a mild cognitive impairment or AD.

Accidents, Traffic↗
PubMed2006

Kidney transplantation with grafts from non-heart-beating donors.

We analyzed the function and outcome of 16 kidney transplants performed in our hospital from non-heart-beating donors who were harvested at other hospitals. The cold ischemia times were longer and the delayed graft function rates higher. However, graft function was no different from that of kidneys from heart-beating donors. This experience has encouraged us to use this type of donor to reduce the transplant waiting list.

Aged↗
PubMed2006

Immunomodulation using the recombinant monoclonal human B7-DC cross-linking antibody rHIgM12.

A patient with Waldenstrom's macroglobulinaemia expresses a high titre IgM antibody in serum that binds both mouse and human dendritic cells (DC) in a B7-DC (PD-L2)-dependent manner. We have reported previously that purified antibody from patient serum activates immature and mature DC in vitro, enhancing the ability of these professional antigen-presenting cells to activate naive T cells, take up antigen, resist a cytokine-depleted environment and secrete immunomodulatory cytokines, such as interleukin (IL)-6 and tumour necrosis factor (TNF)-alpha. Systemic treatment of experimental animals with this antibody induces potent anti-melanoma immunity and modulates protectively the recall response against antigen challenge through the airway in an experimental model of inflammatory airway disease. Here we describe a monoclonal IgM antibody derived from this serum immunoglobulin that recapitulates each of these earlier observations, providing direct evidence that M protein from the Waldenstrom's patient mediates these potent immunomodulatory effects. Furthermore, cell lines expressing this recombinant form of the human antibody provide the basis for developing this reagent for clinical application.

Amino Acid Sequence↗
PubMed2006

Ex vivo expansion of umbilical cord blood CD34 cells in a closed system: a multicentric study.

BACKGROUND AND OBJECTIVES: The Dideco 'Pluricell System' is a CE-marked medical device allowing haematopoietic stem cell (HSC) expansion. It comprises a kit of cGMP cytokines and reagents, a closed-cell expansion chamber and a cell-washing set. We tested the system in a multicentric study by expanding CD34(+) cells from eight fresh umbilical cord blood (UCB) samples. MATERIALS AND METHODS: During culture, the mean nucleated cell (NC) count, the mean CD34(+) cell count, fold expansion, viability and apoptosis were measured. Clonogenic assays and immunophenotypical characterization were performed on days 0, 7 and 12. On the expanded cellular product, in three cases cell genotyping, endotoxin level and mycoplasma detection (by polymerase chain reaction) were performed. RESULTS: The mean CD34(+) cell expansion on days 7 and 12 was sevenfold and 12-fold respectively and the mean NC expansion was 69-fold and 180-fold. The mean NC viability on day 12 was 96.9% (94.4-99.1). After 12 days, granulocyte-macrophage colony-forming units (GM-CFU) showed a 20-fold increase: a slight increase in CD34(+) cell apoptosis was observed during culture. In all of three cases neither chromosomal alterations nor mycoplasma contamination was detected. No significant endotoxin levels were detected after expansion. CONCLUSIONS: The device allows the ex vivo expansion of NC and CD34(+) cells in a closed system. The expanded cellular product is a mixture of progenitors (CD34(+) cells) and differentiated (mainly myeloid and megakaryocytic) cells. To reduce cell apoptosis, more frequent cell feeding during culture should be tested.

Antigens, CD34↗
PubMed2006

Dynamic role of kallikrein 6 in traumatic spinal cord injury.

Kallikrein 6 (K6) is a member of the kallikrein gene family that comprises 15 structurally and functionally related serine proteases. In prior studies we showed that, while this trypsin-like enzyme is preferentially expressed in neurons and oligodendroglia of the adult central nervous system (CNS), it is up-regulated at sites of injury due to expression by infiltrating immune and resident CNS cells. Given this background we hypothesized that K6 is a key contributor to the pathophysiology of traumatic spinal cord injury (SCI), influencing neural repair and regeneration. Examination of K6 expression following contusion injury to the adult rat cord, and in cases of human traumatic SCI, indicated significant elevations at acute and chronic time points, not only at the injury site but also in cord segments above and below. Elevations in K6 were particularly prominent in macrophages, microglia and reactive astrocytes. To determine potential effects of elevated K6 on the regeneration environment, the ability of neurons to adhere to and extend processes on substrata which had been exposed to recombinant K6 was examined. Limited (1 h) or excess (24 h) K6-mediated proteolytic digestion of a growth-facilitatory substrate, laminin, significantly decreased neurite outgrowth. By contrast, similar hydrolysis of a growth-inhibitory substrate, aggrecan, significantly increased neurite extension and cell adherence. These data support the hypothesis that K6 enzymatic cascades mediate events secondary to spinal cord trauma, including dynamic modification of the capacity for axon outgrowth.

Adolescent↗
PubMed2005

LED fluorescence spectroscopy for direct determination of monoamine oxidase B inactivation.

In this work, we report an alternative assay for the determination of the inhibitory effect on monoamine oxidase B (MAO-B) activity of probe compounds. Enzyme MAO-B exhibits fluorescence emissions when it is excited at 412 nm. Using an inexpensive blue LED-like excitation source, we measured the quenching of fluorescence intensity of MAO-B enzyme during the reaction with inhibitors. The applicability of the procedure is demonstrated by assays with l-deprenyl and berberine as inhibitors through the use of fluorescence studies. The IC(50) values of l-deprenyl and berberine were 0.04 and 90 microM, respectively. The K(I) values were 0.020 and 47 microM for l-deprenyl and berberine, respectively. These IC(50) and K(I) values were similar to the values obtained with a standard method. These results demonstrate the feasibility of this method as an alternative to follow the inhibitory effect on MAO-B.

Animals↗
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

A randomized controlled crossover trial of aspirin for fatigue in multiple sclerosis.

Pharmacotherapeutic options for multiple sclerosis (MS)-related fatigue are limited. Thirty patients were randomly assigned to aspirin (ASA) 1,300 mg/day or placebo in a double-blind crossover study. Results favored ASA for the main clinical outcomes: Modified Fatigue Impact Scale scores (p = 0.043) and treatment preference (p = 0.012). There were no significant adverse effects. The results warrant further study and support a role for ASA-influenced mechanisms, perhaps immunologic, in the generation of MS-related chronic fatigue.

Administration, Oral↗
PubMed2005

First report of VanA Enterococcus gallinarum dissemination within an intensive care unit in Argentina.

Enterococcusgallinarum is intrinsically resistant to low levels of vancomycin and has been described as a colonizing microorganism causing bacteraemia and infection among immunosupresed patients. Between August 2000 and February 2001, 15 highly glycopeptide-resistant E. gallinarum isolates, one from blood and the remaining from rectal swabs, were recovered in a general hospital of Buenos Aires Province, Argentina. All isolates were characterized by biochemical assays, and displayed MICs of vancomycin in the range 16-128 mg/l and MICs of teicoplanin in the range 16-32 mg/l. In all cases, PCR analysis yield positive results for both vanC1 and vanA genes. E. gallinarum isolates were classified as two clonal types by SmaI-PFGE: clone A (n = 8) and clone B (n = 7) and both harboured a transferable vanA element.

Anti-Bacterial Agents↗
PubMed2005

3-Hydroxyglutaric acid moderately impairs energy metabolism in brain of young rats.

3-Hydroxyglutaric acid (3HGA) accumulates in the inherited neurometabolic disorder known as glutaryl-CoA dehydrogenase deficiency. The disease is clinically characterized by severe neurological symptoms, frontotemporal atrophy and striatum degeneration. Because of the pathophysiology of the brain damage in glutaryl-CoA dehydrogenase deficiency is not completed clear, we investigated the in vitro effect of 3HGA (0.01-5.0mM) on critical enzyme activities of energy metabolism, including the respiratory chain complexes I-V, creatine kinase isoforms and Na(+),K(+)-ATPase in cerebral cortex and striatum from 30-day-old rats. Complex II activity was also studied in rat C6-glioma cells exposed to 3HGA. The effect of 3HGA was further investigated on the rate of oxygen consumption in mitochondria from rat cerebrum. We observed that 1.0mM 3HGA significantly inhibited complex II in cerebral cortex and C6 cells but not the other activities of the respiratory chain complexes. Creatine kinase isoforms and Na(+),K(+)-ATPase were also not affected by the acid. Furthermore, no inhibition of complex II activity occurred when mitochondrial preparations from cerebral cortex or striatum homogenates were used. In addition, 3HGA significantly lowered the respiratory control ratio in the presence of glutamate/malate and succinate under stressful conditions or when mitochondria were permeabilized with digitonin. Since 3HGA stimulated oxygen consumption in state IV and compromised ATP formation, it can be presumed that this organic acid might act as an endogenous uncoupler of mitochondria respiration. Finally, we observed that 3HGA changed C6 cell morphology from a round flat to a spindle-differentiated shape, but did not alter cell viability neither induced apoptosis. The data provide evidence that 3HGA provokes a moderate impairment of brain energy metabolism and do not support the view that 3HGA-induced energy failure would solely explain the characteristic brain degeneration observed in glutaryl-CoA dehydrogenase deficiency patients.

Animals↗
PubMed2005

Default from colposcopy and loop excision electrocautery procedure appointments in a military clinic.

OBJECTIVE: To determine the extent of nonadherence and impediments to care in a military colposcopy and loop excision electrocautery procedure (LEEP) clinic. MATERIALS AND METHODS: The nonadherence rate for colposcopy and LEEP appointments was determined for a 6-month period at Walter Reed Army Medical Center. Nonadherence was defined as failure to keep an appointment or cancellation within 24 hours of the scheduled time. A nurse coordinator telephoned all nonadherent women. Women who agreed to participate were administered a structured survey to elicit their reasons for default from their appointments. RESULT: Sixty-one (15%) of 405 women were nonadherent. Of the 61 nonadherent women, 55 (90%) agreed to participate, 4 (7%) were unable to be contacted, and 2 (3%) declined participation. The average age of participants was 30 years. Beneficiary status of the 55 women was as follows: dependent, 27 (49%); active duty, 25 (45%); retired, 2 (4%); and veteran, 1 (2%). The most common reasons for default overall for 55 women were onset of menses (15 [27%]), unplanned family or personal event (9 [16%]), forgetting (8 [15%]), and work conflict (7 [13%]). Leading reasons for 25 active duty women included work conflict (7 [28%]) and menses (6 [24%]). Leading reasons for 27 dependent women included menses (9 [33%]), unplanned family or personal event (6 [22%]), and forgetting (5 [19%]). CONCLUSIONS: Despite unrestricted access to care in the military clinic, the default rate was similar to rates reported for civilian clinics. Previsit interventions likely to improve compliance include sending informational packets to patients, better attention to scheduling around the time of expected menses, and initiating an appointment reminder system. To decrease the high percentage of nonadherence attributable to work conflicts for active duty women, supervisors need to be better informed about both medical and deployment implications of an unevaluated abnormal Pap smear.

Adult↗
PubMed2005

Clinical course, pathological correlations, and outcome of biopsy proved inflammatory demyelinating disease.

BACKGROUND: A pathological classification has been developed of early active multiple sclerosis (MS) lesions that reveals four patterns of tissue injury: I-T cell/macrophage associated; II-antibody/complement associated; III-distal oligodendrogliopathy, and IV-oligodendrocyte degeneration in the periplaque white matter. Mechanisms of demyelination in early MS may differ among the subgroups. Previous studies on biopsied MS have lacked clinicopathological correlation and follow up. Critics argue that observations are not generalisable to prototypic MS. OBJECTIVE: To describe the clinicopathological characteristics of the MS Lesion Project biopsy cohort. METHODS: Clinical characteristics and disability of patients with pathologically confirmed inflammatory demyelinating disease (excluding ADEM) classified immunopathologically (n = 91) and patients from the Olmsted County MS prevalence cohort (n = 218) were determined. RESULTS: Most patients who underwent biopsy and had pathologically proved demyelinating disease ultimately developed definite (n = 70) or probable (n = 12) MS (median follow up 4.4 years). Most had a relapsing remitting course and 73% were ambulatory (EDSS < or =4) at last follow up. Nine patients remained classified as having an isolated demyelinating syndrome at last follow up. Patients with different immunopathological patterns had similar clinical characteristics. Although presenting symptoms and sex ratios differed, the clinical course in biopsy patients was similar to the prevalence cohort. Median EDSS was <4.0 in both cohorts when matched for disease duration, sex, and age. CONCLUSIONS: Most patients undergoing biopsy, who had pathologically confirmed demyelinating disease, were likely to develop MS and remain ambulatory after a median disease duration of 4.4 years. The immunopathological patterns lacked specific clinical correlations and were not related to the timing of the biopsy. These data suggest that pathogenic implications derived largely from MS biopsy studies may be extrapolated to the general MS population.

Adolescent↗
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↗