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Biomedical subjects

M Rodriguez

Publications and source records attributed to M Rodriguez.

At least 253 records · Page 14Linked to original sources
PubMed1997

Nuclear localization of I kappa B alpha promotes active transport of NF-kappa B from the nucleus to the cytoplasm.

I kappa B alpha tightly regulates the transcriptional activity of NF-kappa B by retaining it in the cytoplasm in an inactive form. In the present work, we report that I kappa B alpha, when expressed in the nuclear compartment, not only abrogates NF-kappa B/DNA interactions and NF-kappa B-dependent transcription, but also transports NF-kappa B back to the cytoplasm. This function of I kappa B alpha is insured by a nuclear export sequence located in the C-terminal domain of I kappa B alpha and homologous to the previously described export signal found in HIV-1 Rev protein as well as in PKI (the inhibitor of the catalytic subunit of protein kinase A). Thus, inhibition of NF-kappa B/DNA binding and the consecutive efficient nuclear export of the transcription factor of I kappa B alpha could represent an important mechanism for the control of the expression of NF-kappa B-dependent genes.

Amino Acid Sequence↗
PubMed1997

Evidence for both abnormal set point of PTH stimulation by calcium and adaptation to serum calcium in hemodialysis patients with hyperparathyroidism.

In vitro studies of parathyroid glands removed from dialysis patients with secondary hyperparathyroidism and hypercalcemia have demonstrated the presence of an increased set point of parathyroid hormone (PTH) stimulation by calcium (set point [PTHstim]), suggesting an intrinsic abnormality of the hyperplastic parathyroid cell. However, clinical studies on dialysis patients have not observed a correlation between the set point (PTHstim) and the magnitude of hyperparathyroidism. In the present study, 58 hemodialysis patients with moderate to severe hyperparathyroidism (mean PTH 780 +/- 377 pg/ml) were evaluated both before and after calcitriol treatment to establish the relationship among PTH, serum calcium, and the set point (PTHstim) and to determine whether changes in the serum calcium, as induced by calcitriol treatment, modified these relationships. Calcitriol treatment decreased serum PTH levels and increased the serum calcium and the setpoint (PTHstim); however, the increase in serum calcium was greater than the increase in the setpoint (PTHstim). Before treatment with calcitriol, the correlation between the set point (PTHstim) and the serum calcium was r = 0.82, p < 0.001, and between the set point (PTHstim) and PTH was r = 0.39, p = 0.002. After treatment with calcitriol, the correlation between the set point (PTHstim) and the serum calcium remained significant (r = 0.70, p < 0.001), but the correlation between the set point (PTHstim) and PTH was no longer significant (r = 0.09); moreover, a significant correlation was present between the change in the set point (PTHstim) and the change in serum calcium that resulted from calcitriol treatment (r = 0.73, p < 0.001). The correlation between the residual values (deviation from the regression line) of the set point (PTHstim), derived from the correlation between PTH and the set point (PTHstim), and serum calcium was r = 0.77, p < 0.001 before calcitriol and r = 0.72, p < 0.001 after calcitriol. In conclusion, the set point (PTHstim) increased after a sustained increase in the serum calcium, suggesting an adaptation of the set point to the existing serum calcium; the increase in serum calcium resulting from calcitriol treatment was greater than the increase in the set point (PTHstim); the set point (PTHstim) was greater in hemodialysis patients with higher serum PTH levels; and the correlation between PTH and the set point (PTHstim) may be obscured because the serum calcium directly modifies the set point (PTHstim).

Adaptation, Physiological↗
PubMed1997

[18F] FDG PET in gastric non-Hodgkin's lymphoma.

The possibility of using [18F] FDG PET for assessment of tumor extension in primary gastric non-Hodgkin's lymphoma (NHL) was studied in 8 patients (6 high-grade and 2 low-grade, one of the MALT type) and in a control group of 7 patients (5 patients with NHL without clinical signs of gastric involvement, 1 patient with NHL and benign gastric ulcer and 1 patient with adenocarcinoma of the stomach). All patients with gastric NHL and the two with benign gastric ulcer and adenocarcinoma, respectively, underwent endoscopy including multiple biopsies for histopathological diagnosis. All patients with high-grade and one of the two with low-grade NHL and the patient with adenocarcinoma displayed high gastric uptake of [18F] FDG corresponding to the pathological findings at endoscopy and/or CT. No pathological tracer uptake was seen in the patient with low-grade gastric NHL of the MALT type. In 6/8 patients with gastric NHL, [18F] FDG PET demonstrated larger tumor extension in the stomach than was found at endoscopy, and there was high tracer uptake in the stomach in two patients who were evaluated as normal on CT. [18F] FDG PET correctly excluded gastric NHL in the patient with a benign gastric ulcer and in the patients with NHL without clinical signs of gastric involvement. Although the experience is as yet limited, [18F] FDG PET affords a novel possibility for evaluation of gastric NHL and would seem valuable as a complement to endoscopy and CT in selected patients, where the technique can yield additional information decisive for the choice of therapy.

Aged↗
PubMed1997

Tumour inhomogeneities on magnetic resonance imaging, a new factor with prognostic information in non-Hodgkin's lymphomas.

The prognostic importance of inhomogeneities on magnetic resonance imaging (MRI) in non-Hodgkin lymphomas (NHL) was evaluated. Forty-six consecutive patients with high-grade NHL were examined and, for comparison purposes, 13 patients with low-grade NHL. The degree of inhomogeneity was measured with a quantitative method (IH8) and a subjective evaluation was also performed. Patients with localized disease (stage I), who had all been treated with radiotherapy, had an excellent prognosis, which was independent of the degree of tumour inhomogeneity. In generalized NHL (stages II-IV) treated with chemotherapy, IH8 provided prognostic information in high-grade NHL. Patients with pronounced tumour inhomogeneity, in particular, had a very poor prognosis. The prognostic impact was also seen if the analyses were performed with high-grade and low-grade NHLs grouped together. The inhomogeneities may indicate a mechanism related to treatment failure after chemotherapy, but not after fractionated radiotherapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

Subaxial cervical spine subluxation in rheumatoid arthritis. A retrospective analysis of 16 operated patients after 1-5 years.

We evaluated the clinical and radiological outcomes in 16 patients (15 women) having rheumatoid arthritis with a mean age of 66 (55-77) years, on average 2 (1-5) years after decompression and stabilization, for subaxial subluxation of the cervical spine. The duration of rheumatoid arthritis averaged 30 (10-67) years and the duration of neck symptoms averaged 15 (1-60) months. Preoperatively, 11 of the patients had pain in the neck, all 16 suffered from arm rhizopathy and varying degrees of myelopathy. 4/5 patients with severe myelopathy died within 3 months of surgery. Fixation failure occurred in 7 patients, but had no clinical significance in 5. There were 1 deep infection and 1 nerve root lesion resulting in deltoid weakness. Other complications were dysphagia and donor-site pain. 4 reoperations were performed, 2 extension of fusion, 1 revision of infection, and 1 foraminotomy. Neck pain was reliably relieved, while arm rhizopathy was less positively affected. Myelopathy carried a poor prognosis for relief and its occurrence correlated with death. Early treatment, before significant myelopathy has developed, is recommended. Decompression, both via realignment and bone resection, followed by fusion of the entire cervical spine, is advocated. Due to the poor bone quality and with the presently available implant systems, simultaneous anterior and posterior fixation is beneficial.

Aged↗
PubMed1997

Bovine somatotropin dose titration in lactating dairy ewes. 2. Dose determination and factors affecting the response.

Seventy-four lactating dairy ewes were injected with recombinant bovine somatotropin (bst; sometribove) in a sustained-release formulation. Ewes received 0, 80, 160, or 240 mg of bST/14 d from wk 3 to 8 of lactation (part 1) and 0, 80, or 160 mg of bST/14 d from wk 11 to 18 of lactation (part 2). The optimal dose of bST was studied as well as the factors (lactation stage, lactation number, initial milk production, body weight, and body condition) possibly affecting the increase in milk production following bST injection. Using a quadratic regression model, the maximum theoretical dose was determined to be 181 mg of bST/14 d during the first part of lactation. During the second part of lactation, 143 mg of bST/14 d was the maximum theoretical dose. The increment of milk production did not vary with lactation number, but first lactation ewes, in general, responded better than did multiparous ewes. Relative to initial milk production, improvement was greatest for ewes with average milk production (1500 ml/d) that received a dose of 192.3 mg of bST/14 d during the first part of lactation; improvement was also measured from the highest producers (2000 ml/d) during the second part of lactation. The best response was obtained from ewes with average body condition (score 3 on a five-point scale where 1 = thin to 5 = fat) and a dose of 200 mg of bST/14 d during the first part of lactation; during the second part of lactation, body condition score had no effect. Body weight had no effect on the increment of production at any time.

Animal Nutritional Physiological Phenomena↗
PubMed1997

Identification of multiple sclerosis-associated genes.

Multiple sclerosis (MS) is a complex genetic trait. Analyses to identify genetic variants that increase susceptibility to MS have primarily focused on candidate genes, either in family linkage investigations or in association (linkage disequilibrium) studies in sporadic cases and control subjects. Most of the candidate genes considered to date either influence immune function or encode structural myelin proteins. Recently, three preliminary whole genomic surveys were completed, and they reveal multiple loci of possible genetic linkage that are worthy of further study. No convincing evidence for a single strong locus has emerged from analysis of the three studies. Linkage promises to focus the future choice of candidate genes for further investigation.

Complement System Proteins↗
PubMed1997

The epidemiology of multiple sclerosis.

Although the cause of multiple sclerosis (MS) is unknown, epidemiologic studies support both genetic and environmental components of susceptibility. Reports of clusters, small "epidemics," geographic variation in prevalence, and alteration of MS susceptibility by migration support an environmental factor (or factors). The higher risk for MS in Europeans and in relatives of patients and the existence of MS-resistant ethnic groups support genetic predisposition. Findings from epidemiologic studies are most consistent with an environmental influence occurring on a background of genetic susceptibility as the cause of MS. Currently, there is little evidence for a single or unique environmental cause of MS.

Disease Outbreaks↗
PubMed1997

Sudden cardiac death during exercise due to an isolated multiple anomaly of the left coronary artery in a 12-year-old girl: clinicopathologic findings.

A 12-year-old girl was taken to the Virgen Macarena Universitary Hospital in Seville, Spain, complaining of abdominal pain, nausea, palpitations, and difficulty in breathing. Her school teacher informed that the girl collapsed after a 100-m race at sports in school. Emergency rescue personnel found the patient pale, in a cold sweat, with low peripheral perfusion. Initial ECF revealed supraventricular tachycardia (150 bpm), right bundle branch block and left anterior hemiblock that, eventually, progressed to full cardiac arrest. At autopsy, an isolated multiple congenital anomaly of the left coronary artery was found (initial segment anomaly; course anomaly and tunneled coronary artery anomaly). In our opinion, this appears to be the first reported case of exercise-related sudden cardiac death, due to an isolated multiple congenital anomaly of the left coronary artery (at the origin, on the course and at the termination).

Child↗
PubMed1997

Interferon alpha/beta mediates early virus-induced expression of H-2D and H-2K in the central nervous system.

Cells of the central nervous system (CNS) normally do not express detectable levels of major histocompatibility complex (MHC) Class I antigens. However, MHC Class I expression can be induced after virus infection. We tested the hypothesis that virus-induced Class I expression is mediated by lymphocytes or cytokines using lymphocyte- and cytokine-deficient mice. We used Theiler's murine encephalomyelitis virus (TMEV), which induces CNS demyelination that maps genetically to the D region of MHC Class I and is associated with high levels of Class I products. TMEV infection of severe combined immunodeficiency (SCID) and recombination activation gene-1-deficient mice, which lack B and T lymphocytes, resulted in equivalent H-2D and H-2K expression in brain and spinal cord, according to analysis of the area and intensity of immunoperoxidase staining. Class I antigens were demonstrated as early as 6 hours after infection, and they were more widely distributed than viral RNA, indicating that expression was induced indirectly via a soluble factor. To determine whether cytokines induced the expression, we infected mice lacking receptors for interferon-alpha/beta (IFN-alpha/beta R (-/-)), interferon-gamma (IFN-gamma R(-/-)), and tumor necrosis factor-alpha (TNFRp55(-/-)). TMEV-infected IFN-gamma R(-/-) and TN-FRp55(-/-) mice expressed Class I antigens in the CNS, whereas IFN-alpha/beta R(-/-) mice did not, establishing that IFN-alpha/beta mediated the expression. In contrast to the equivalent expression in SCID mice, we observed greater area and higher intensity of H-2D versus H-2K antigens in infected SCID mice reconstituted with normal spleen cells. Collectively, the data indicate that after TMEV infection, early generalized MHC Class I expression is mediated by IFN-alpha/beta independently of lymphocytes, but the differential regulation of H-2D over H-2K may be controlled by B and/or T lymphocytes.

Animals↗
PubMed1997

A follow-up study of multibacillary Hansen's disease patients treated with multidrug therapy (MDT) or MDT + immunotherapy (IMT).

Multibacillary (MB) leprosy patients treated with multidrug therapy (MDT) or MDT + immunotherapy (IMT) with BCG + heat-killed Mycobacterium leprae were tested annually for their ability to proliferate in vitro to the mycobacterial antigens BCG, M. leprae soluble extract, and intact M. leprae. IgM antibody responses to phenolic glycolipid I (PGL-I) were measured, as well as serum nitrite levels in patients' sera, before, during and after treatment. Patients who received only MDT did not present cellular reactivity to intact M. leprae antigens, in contrast to the results obtained with BCG, which elicited reactivity at time zero, that increased after treatment. Regarding PGL-I antibody variations in relation to the initial value, we observed a statistically significant marked decrease at the end of 2 years which continued to fall in successive evaluations. MB patients showed high initial serum nitrite concentrations which dropped drastically with treatment. This decay was apparently associated with the bacillary load present in these patients. The group submitted to IMT + MDT showed high and long-lasting T-cell responses to mycobacterial antigens in a significant number of initially unresponsive MB patients. There was a marked increase to M. leprae soluble extract and BCG, as well as a more variable response to whole bacilli. The antibody levels in this group of patients are sustained for a somewhat longer period and decreased more slowly during the 5-year follow up.

Antibodies, Bacterial↗
PubMed1997

Mutations resulting in transient and localized degeneration in the developing zebrafish brain.

In a large-scale mutagenesis screen in the zebrafish, Danio rerio, we have identified a heterogeneous group of 30 recessive, embryonic lethal mutations characterized by degeneration in the developing central nervous system that is either transient or initially localized to one area of the brain. Transient degeneration is defined as abnormal cell death occurring during a restricted period of development. Following degeneration, the affected structures do not appear to regenerate. In each case degeneration is identified after somitogenesis is complete and is not associated with visually identified patterning defects. These 30 mutations, forming 21 complementation groups, have been classified into four phenotypic groups: group 1, transient degeneration (13 mutations); group 2, spreading degeneration, early onset, in which degeneration is initially confined to the optic tectum but subsequently spreads to other areas of the central nervous system (7 mutations); group 3, late-onset degeneration, initially identified after 4 days (6 mutations); and group 4, degeneration with abnormal pigmentation (4 mutations). Although apoptotic cells are seen in the retina and tectum of all mutants, the distribution, temporal progression, and severity of degeneration vary between mutations. Several mutations also show pleiotropic effects, with degeneration involving extraneural structures including the pharyngeal arches and pectoral fins. We discuss some of the pathways important for cell survival in the nervous system and suggest that these mutations will provide entry points for identifying genes that affect the survival of restricted neural populations.

Animals↗
PubMed1996

The balance between persistent virus infection and immune cells determines demyelination.

We addressed the contributions of persistent virus infection and immune cells to the pathogenesis of Theiler's virus-induced demyelination, a model for human multiple sclerosis. We developed a model involving the transfer of spleen cells into immunodeficient C.B-17-scid (SCID) mice, which normally die of overwhelming virus encephalitis without demyelination when infected with Theiler's virus. Adoptive transfer of nonimmune spleen cells from BALB/c mice into SCID mice resulted in the survival of all mice. However, these mice developed extensive demyelination and virus Ag/RNA persistence in the spinal cord white matter. The most demyelination was observed when mice received an intermediate number of spleen cells (1.8-7.5 x 10(6)), whereas too few cells (0.5 x 10(6)) did not ameliorate the SCID phenotype, and too many cells (30 x 10(6)) resulted in almost complete viral clearance with minimal demyelination. Adoptive transfer of spleen cells depleted of either CD4+ or CD8+ T cells produced vacuolar demyelination associated with virus persistence. In contrast, reconstitution with both CD4+ and CD8+ T cells produced less severe demyelination and partial clearance of virus. These experiments support the hypothesis that demyelination is the result of a balance between persistent virus infection and immune injury mediated by either CD4+ or CD8+ T cells.

Adoptive Transfer↗
PubMed1996

Accumulation of tyrosine hydroxylase messenger RNA molecules in the rat mesencephalon by chronic caffeine treatment.

In the present study we assessed the effect of chronic treatment with caffeine on the levels of the messenger RNA molecule encoding the enzyme tyrosine hydroxylase (TH) by in situ hybridization histochemistry in the ventral tegmental area (VTA) and the substantia nigra compacta (SNc) of the rat brain. Animals that received caffeine for nine consecutive days at doses of 20, 40 and 80 mg/kg of body weight displayed increased TH mRNA levels in the SNc (up to 64% above vehicle-injected controls) and the VTA (33% above controls). Moreover, the increases observed at 80 mg/kg of caffeine were prevented by concurrent administration of the non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 (0.25 mg/kg). These results demonstrate that chronic exposure to caffeine, an adenosine A2 receptor antagonist, alters the levels of expression of the mRNA encoding the rate limiting enzyme in catecholamine biosynthesis.

Animals↗
PubMed1996

The role of radioimmunoscintigraphy and computed tomography scan prior to reassessment laparotomy of patients with ovarian carcinoma. A preliminary report.

BACKGROUND: Accurate evaluation of patients with ovarian carcinoma who have completed primary therapy often requires surgical exploration. Radioimmunoscintigraphy (RIS) represents an evolving technique that may allow noninvasive detection and localization of persistent or recurrent disease in these patients. METHODS: Our prospective, blinded study enrolled patients with normal CA 125 levels and no clinical evidence of disease after primary cytoreductive surgery and cytotoxic chemotherapy for ovarian carcinoma. Each patient underwent RIS using Indium-satumomab pendetide (labeled antibody B72.3 to the tumor-associated antigen TAG-72) and abdominal/pelvic computed tomography (CT) prior to reassessment laparotomy. RESULTS: Twenty patients were enrolled from January 1994 to January 1995. Two patients with negative RIS scans refused reassessment laparotomy and were without evidence of disease > 15 months from the study. Twelve of the remaining 18 patients (66.7%) had histologically proven disease at reassessment laparotomy. RIS images indicated the presence of disease in all 12 patients, whereas CT scans detected disease in only 2 patients. In three of five patients, biopsy-proven microscopic disease (no gross disease at the time of laparotomy) was found only in specimens obtained by RIS-directed biopsies. RIS was superior to CT in sensitivity (100% vs. 16.7%), accuracy (72% vs. 33%), and negative predictive value (100% vs. 28.6%) (P < 0.005). CONCLUSIONS: Routine use of CT is of limited value in the assessment of ovarian carcinoma patients with negative physical examinations and normal CA 125 levels. With its high level of sensitivity and negative predictive value, RIS may play a role in the detection of persistent disease in this population and aid in the classification of patients into three distinct groups: those with gross residual disease, small volume or microscopic disease, and no disease. Separation of this heterogenous group without surgery may help guide subsequent consolidation therapy. However, attaining a high level accuracy with RIS, depends on optimizing the method of image acquisition, the timing of scans, and the reconstruction of data.

Animals↗