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Biomedical subjects

M Rodriguez

Publications and source records attributed to M Rodriguez.

At least 217 records · Page 12Linked to original sources
PubMed1998

Psychosocial adjustment among Central American immigrants with disabilities: an exploratory study.

This is an exploratory study that investigated factors influencing the psychosocial adjustment of Central American immigrants with disabilities. The relationships between stress, and perception of disability severity and (a) depression and (b) anxiety were assessed. Furthermore, this study investigated whether social support moderated the impact of stress and severity of disability on depression and anxiety. Stress, severity of disability, and social support explained a high percentage (54%) of the variance in depression. High levels of stress, increased perceptions of severity of disability, and low social support were associated with increased depression. The interactions between support and stress and between support and disability severity did not significantly add to the original model which predicted depression. Main effects were found for stress, disability severity, and the interaction between support and disability severity. Stress and social support significantly accounted for 31% of the variance in anxiety. Increased stress and decreased social support were associated with greater levels of anxiety. The interaction between support and stress did not significantly predict anxiety. Implications of the study in terms of future research and intervention programs targeting mental health outcomes for Latino immigrants with disabilities are discussed.

Acculturation↗
PubMed1998

Teaching community-oriented primary care through longitudinal group projects.

BACKGROUND: Though community-oriented primary care (COPC) has been advocated as an effective way of addressing health problems of communities, it is neither widely understood nor frequently practiced. Because COPC requires an extended period of time, as well as an approach and skills not generally learned in medical training, effectively incorporating COPC training into medical education is difficult and not frequently attempted. This paper describes a COPC curriculum for family practice residents based on required participation in a longitudinal group project. METHODS: Residents participated in successive groups that completed a COPC project over a 2-year period. Twenty-two of 26 PGY-2 residents completed an attitude and knowledge test before and after participation in the curriculum. A qualitative evaluation of the curriculum was also performed. RESULTS: Pretest and posttest responses showed significant improvement in residents' knowledge about COPC and a small but significant decline in attitudes toward COPC. Residents' reactions to the curriculum in the qualitative evaluation were both positive and negative. Residents enjoyed the group process and found it intellectually stimulating. Many reported, however, that they did not feel ownership of the project, that working through the four-step systematic COPC process was slow and cumbersome, and that they had learned only part of the COPC process. Residents consistently reported becoming more aware of the importance of discussing the focus of the project (i.e., childhood discipline or domestic violence) with their patients and feeling more comfortable initiating such discussions. CONCLUSIONS: A COPC curriculum based on required participation in a 2-year group project promoted completion of substantial projects. There were trade-offs in resident experience, including loss of continuity for individual residents. Effectively teaching COPC and engaging residents in community-oriented activities remains a challenge.

Community Health Services↗
PubMed1998

Computed tomography, magnetic resonance imaging and positron emission tomography in non-Hodgkin's lymphoma.

Certain aspects of the use of CT, MR imaging and PET were evaluated in patients with non-Hodgkin's lymphoma (NHL) with the aim of determining whether these methods may provide practical guidance for improving the management of these patients. Subjective evaluation of the tumor pattern on CT images, and quantification of tracer uptake using 11C methionine (11C Met) and [18F] fluorodeoxyglucose (18FDG) PET in patients with NHL, were performed to determine their relations to malignancy grade. An inhomogeneous tumor pattern (I) was found on CT in 75% of high-grade tumors, whereas 68% of low-grade tumors were homogeneous (H). Sixteen (94%) of the 17 tumors with a severely inhomogeneous pattern (I) were high-grade NHL, while 22 (72%) of the 29 homogeneous tumors (H) were low-grade. All tumors were clearly visualized with both 11C Met and 18FDG PET. The uptake values for 18FDG were significantly-higher in high- than in low-grade tumors, while no significant differences between the prognostic groups were found for 11C Met. A subjective evaluation of the tumor pattern on CT and on MR images was performed. An inhomogeneity index (IH8) was also used in MR images to make a quantitative assessment of the degree of inhomogeneity to determine their relation to prognosis. Patients with localized NHL, treated with radiotherapy, had an excellent prognosis irrespective of the degree of inhomogeneity, while patients with generalized disease, treated with chemotherapy, had a poor prognosis if the tumors were heterogeneous. Among chemotherapy-treated patients, all 9 patients with high IH8 values (> 2.56) on MR images and 9 out of 11 patients with severe inhomogeneities on CT images died. All patients with gastric NHL except for one patient with low-grade NHL of the MALT type displayed high 18FDG uptake at PET corresponding to the pathological findings at endoscopy and/or CT. 18FDG correctly excluded gastric NHL in a patient with benign gastric ulcer, but was unable to discriminate between gastric NHL and gastric carcinoma. The results suggest that 18FDG PET may demonstrate the extension of NHL in the gastric wall more accurately than CT and endoscopy. The prognostic importance of the size of a residual mass after completion of chemotherapy, and of tumor regression rates during chemotherapy, was evaluated in patients with high-grade NHL. Neither a large tumor size before treatment nor a large residual tumor after treatment correlated with relapse. It appears, however, as if the response rate halfway through the therapy may predict the recurrence rate, although statistical significance was not reached.

Adolescent↗
PubMed1997

Rapid movement of newly synthesized chicken apolipoprotein AI to trans-Golgi network and its secretion in Madin-Darby canine kidney cells.

MDCK cells were utilized to study the biosynthesis and secretion of chicken apolipoprotein AI (apoAI). A full-length apoAI cDNA in an eukaryotic expression vector was transfected into a MDCK-TGG cell line, expressing a trans-Golgi network (TGN) marker (TGG), and stable clones expressing apoAI were selected. Pulse-chase and cell fractionation studies showed that, compared to gp 80 (an endogenous secretory protein), apoAI was rapidly transported from RER to Golgi complex within 5 min and released from the Golgi complex to the cell exterior by 30 min. Immunofluorescence and three-dimensional laser scanning confocal microscopy revealed that at steady state apoAI was predominantly localized in the TGN. Transferrin uptake experiments showed that apoAI, localized in the TGN, was derived primarily from biosynthetic and not from endocytic routes. ApoAI was secreted in a nonpolarized manner. We suggest that apoAI stays transiently in the TGN prior to its secretion and that the major events of apoAI biosynthesis in vivo and in MDCK cells are conserved. Possible mechanisms of rapid ER to Golgi transport and TGN localization of apoAI are discussed.

Animals↗
PubMed1997

Monoclonal remyelination-promoting natural autoantibody SCH 94.03: pharmacokinetics and in vivo targets within demyelinated spinal cord in a mouse model of multiple sclerosis.

Chronic inflammatory demyelination of the central nervous system is usually incompletely repaired. However, we previously reported that in vivo treatment with monoclonal antibody SCH 94.03 (produced using spinal cord homogenate as an immunogen) increased myelin repair 4-fold in the Theiler's virus mouse model of chronic progressive multiple sclerosis (Miller et al., 1994; J. Neurosci. 14: 6230-6238). A major issue regarding site and mechanism of action of this antibody is whether SCH 94.03 enters demyelinated CNS lesions and reacts with oligodendrocytes and myelin. To address this question, we radiolabeled SCH 94.03 and studied its distribution into tissues, pharmacokinetics, and binding to cells within demyelinating spinal cord lesions in vivo. SCH 94.03 distributed widely into extracellular water following intraperitoneal injection and was eliminated with a terminal half-life of 3-4.5 days. Only a portion of the total dose (0.4%) entered brain and spinal cord. SCH 94.03 accumulated 1.5-2.0-fold in brain between 1 and 7 days after injection, but its pharmacokinetics were otherwise similar to those of an isotype control IgMkappa antibody. Oligodendrocytes, myelin sheaths and, less frequently, axons were labeled within demyelinating lesions as detected by light and electron microscopic autoradiography. These findings suggest that remyelination-promoting autoantibodies could act within the demyelinating lesion of the central nervous system by binding to the oligodendrocyte, myelin, or axon.

Animals↗
PubMed1997

Peptide ligands of pp60(c-src) SH2 domains: a thermodynamic and structural study.

Thermodynamic measurements, structural determinations, and molecular computations were applied to a series of peptide ligands of the pp60(c-src) SH2 domain in an attempt to understand the critical binding determinants for this class of molecules. Isothermal titration calorimetry (ITC) measurements were combined with structural data derived from X-ray crystallographic studies on 12 peptide-SH2 domain complexes. The peptide ligands studied fall into two general classes: (1) dipeptides of the general framework N-acetylphosphotyrosine (or phosphotyrosine replacement)-Glu or methionine (or S-methylcysteine)-X, where X represents a hydrophobic amine, and (2) tetra- or pentapeptides of the general framework N-acetylphosphotyrosine-Glu-Glu-Ile-X, where X represents either Glu, Gln, or NH2. Dipeptide analogs which featured X as either hexanolamine or heptanolamine were able to pick up new hydrogen bonds involving their hydroxyl groups within a predominantly lipophilic surface cavity. However, due to internal strain as well as the solvent accessibility of the new hydrogen bonds formed, no net increase in binding affinity was observed. Phosphatase-resistant benzylmalonate and alpha,alpha-difluorobenzyl phosphonate analogs of phosphotyrosine retained some binding affinity for the pp60(c-src) SH2 domain but caused local structural perturbations in the phosphotyrosine-binding site. In the case where a reversible covalent thiohemiacetal was formed between a formylated phosphotyrosine analog and the thiol side chain of Cys-188, deltaS was 25.6 cal/(mol K) lower than for the nonformylated phosphotyrosine parent. Normal mode calculations show that the dramatic decrease in entropy observed for the covalent thiohemiacetal complex is due to the inability of the phosphotyrosine moiety to transform lost rotational and translational degrees of freedom into new vibrational modes.

Amino Acid Sequence↗
PubMed1997

Nocturnal hypoglycaemia in IDDM patients younger than 18 years.

The present multicentre study was undertaken to assess the prevalence of nocturnal hypoglycaemia and its determining factors in 117 diabetic children and adolescents, aged 2-18 years and diabetes duration > 1 year in Spain. Each child made 3 measurements of blood glucose (BG) at home at night (between 0000 h and 0600 h) on nine separate nights. A hypoglycaemic event occurred in 12-14% of children in any one night. This is lower than rates for nocturnal hypoglycaemia reported in literature, perhaps because of relatively late mealtimes and different meal content, in Spanish children. Children aged < 7 years were at higher risk of nocturnal hypoglycaemia than older children (p < 0.05). Mean HbA1c from the year before the study and mean HbA1c measured during the closest time to the study were significantly lower in those with nocturnal hypoglycaemia (p < 0.0001). Blood glucose concentrations 2 h before hypoglycaemia did not predict nocturnal hypoglycaemia. The occurrence of low or very low blood glucose concentrations before breakfast was related to a higher risk for nocturnal hypoglycaemia (chi 2 22.97; p < 0.001). No previous symptoms were detectable in 89% of cases.

Adolescent↗
PubMed1997

Increased severity of experimental autoimmune encephalomyelitis, chronic macrophage/microglial reactivity, and demyelination in transgenic mice producing tumor necrosis factor-alpha in the central nervous system.

Tumor necrosis factor-alpha (TNF-alpha) is an inflammatory cytokine implicated in a number of autoimmune diseases. Apoptotic cell death is induced by TNF-alpha in vitro, and has been suggested as one cause of autoimmune pathology, including autoimmune demyelinating diseases where oligodendrocytes are a target of immune attack. TNF-alpha also regulates macrophage activity which could contribute to autoimmune inflammation. We have expressed TNF-alpha at disease-equivalent levels in the central nervous system of transgenic mice, using a myelin basic protein (MBP) promoter. These mice were normal and showed no spontaneous pathology, but they developed experimental autoimmune encephalomyelitis (EAE) with greater severity than nontransgenic controls when immunized with MBP in adjuvant. Unlike nontransgenic controls, EAE then progressed to a nonabating demyelinating disease. Macrophage/microglial reactivity was evident in demyelinating lesions in spinal cord, but T cells were not detected during chronic disease. The participation of TNF-alpha in the demyelinating process is thus more probably due to the perpetuation of macrophage/microglial activation than to direct cytotoxicity of myelin or oligodendroglia.

Animals↗
PubMed1997

Differential generation of class I H-2D- versus H-2K-restricted cytotoxicity against a demyelinating virus following central nervous system infection.

Despite the fact that both H-2K and D molecules are up-regulated in the central nervous system (CNS) following Theiler's murine encephalomyelitis virus (TMEV) infection, resistance in this virus model of multiple sclerosis maps exclusively to D. To address this paradox, we examined the ability of the K and D molecules to present viral antigens to cytotoxic T lymphocytes (CTL). Whereas no virus-specific CTL were detected in the CNS of susceptible B10.Q and B10.S mice 7 days post-infection, D-restricted CTL were identified readily in the CNS of resistant B10 animals. There was no evidence of K-restricted CTL in the CNS of B10 mice at day 7 post-infection. The presence of both K- and D-restricted virus-specific CTL in the spleen of immunized B10 mice demonstrates that the exclusive use of D molecules by CTL in the CNS of mice 7 days post-infection is not due to the inability of the K molecules to present viral peptides to lymphocytes. We conclude that the prominent role of the D locus in determining resistance or susceptibility to TMEV-induced demyelination is determined by factors governing the regulation of the immune response, and not by the presence or absence of CTL precursors capable of recognizing viral peptides presented by the K and D antigen-presenting molecules, or by differences in the ability of the K and D molecules to present viral peptides.

Animals↗
PubMed1997

5-Fluorouracil and levamisole exacerbate demyelination in susceptible mice infected with Theiler's virus.

A multifocal inflammatory leukoencephalopathy is associated with the administration of 5-fluorouracil (5-FU), a pyrimidine analogue, and levamisole (LE), an immunomodulator, in patients receiving adjuvant therapy for colon cancer. Cerebral biopsy demonstrated features indistinguishable from multiple sclerosis. We tested whether administration of these agents directly resulted in inflammatory demyelination in mice or whether they exacerbated demyelination in a host predisposed to myelin injury. We used mice intracerebrally infected with Theiler's murine encephalomyelitis virus (TMEV) which serves as an excellent model for multiple sclerosis. Varying dosages of 5-FU (240 micrograms-2.4 mg) and LE (40 micrograms-1 mg) were administered alone or in combination on a fixed schedule to 52 normal SJL mice and 61 Theiler's virus-infected mice (51 SJL/J mice susceptible to demyelination; 10 C57BL10 mice resistant to demyelination). Controls included 6 noninfected SJL and 26 infected mice (16 susceptible; 10 resistant) treated with phosphate-buffered saline (PBS). Inflammation or demyelination was not detected in brains or spinal cords of noninfected SJL mice treated with 5-FU and/or LE. TMEV-susceptible SJL mice treated with LE alone or in combination with 5-FU demonstrated more extensive inflammation and demyelination at Day 45 than mice treated with PBS. Demyelination was accelerated in infected animals treated with these agents at 45 days but at 70 days a significant difference in extent of demyelination was no longer appreciated between treatment and control groups. Treatment with 5-FU and LE did not convert normally resistant TMEV-infected C57BL/10 mice to demyelination. These experiments support the hypothesis that 5-FU and LE may exacerbate inflammatory demyelination in a susceptible host.

Adjuvants, Immunologic↗
PubMed1997

Massive subcutaneous and intraosseous fat necrosis associated with pancreatitis. Natural evolution of the radiographic picture.

A 44-year-old man developed high fever, polyarthralgias, erythematous tender nodules and plaques on feet, ankles, knees and dorsum of the hands, as well as swelling of ankles and several joints of hands and feet. Laboratory evaluation showed high serum pancreatic amylase and lipase. Histological study of a subcutaneous nodule demonstrated fat necrosis. X-ray examination revealed numerous lytic lesions involving cancellous and cortical bone in phalanges, metacarpals, radius, tibia, tarsus and metatarsals, with areas of widened bone. The patient never referred any abdominal symptom. He evolved favourably within the following months. A year later, resolution of most of the bone lesions was observed.

Bone Diseases↗
PubMed1997

The controversy surrounding the pathogenesis of the multiple sclerosis lesion.

The main issues in multiple sclerosis research revolve around four fundamental questions. (1) What initiates the disease-that is, autoimmune T cells, a virus, or a toxin? (2) Is the inflammatory response primary to the development of demyelination, or is it a secondary response to injury? (3) Is the oligodendrocyte, the myelin-producing cell, the primary target? (4) How can myelin repair be promoted? This review focuses on the controversies revolving around these important questions. Although many investigators believe that T-cell receptors on CD4+ cells interact with myelin antigens to initiate an inflammatory cascade that leads to myelin destruction, others maintain that a viral agent may have a direct or indirect role in the pathogenesis of multiple sclerosis. The concept that the immune system contributes to the tissue destruction in multiple sclerosis is generally accepted; however, the debate about cause versus consequence of the pathologic process remains unresolved, as does the identification of the initial event or focus of the damage. Electron microscopic studies have disclosed evidence of remyelination (albeit often incomplete) in lesions of multiple sclerosis. Enhanced understanding of the factors limiting remyelination could help formulate strategies to promote repair. By innovative experimental design and application of available molecular techniques, the answers to these questions may provide insights on how to prevent or treat multiple sclerosis.

Animals↗
PubMed1997

Motor lateralization, behavioral despair and dopaminergic brain asymmetry after prenatal stress.

This paper presents data suggesting a relationship between rat behavioral despair in the Porsolt test and motor lateralization in the T-maze test. In addition, experimental evidence suggests a functional coupling among dopaminergic systems, behavioral despair and motor lateralization. In the first experiment, female, not male, rats with a high level of behavioral despair showed a low level of behavioral lateralization. The inverse relationship was found in female offspring of mothers stressed during gestation. In comparison with unstressed-mother rats, the female offspring of stressed mothers showed an increase of dopamine (DA) and a decrease of dihydroxyphenylacetic acid (DOPAC) and Homovanillic (HVA) levels and of DOPAC:DA and HVA:DA indexes in the n. accumbens of the right side of the brain. No significant differences were found in the n. accumbens of the left brain. Taken together, the present data provide evidence of a relation between behavioral despair and motor lateralization, suggesting that the biological dopaminergic inervation of n. accumbens could be the basis for this functional coupling. Because the stress of gestant mothers modified these biochemical and behavioral variables, the present study also suggests that lateralization of behavior and emotion during adulthood can be modified by prenatal variables.

Animals↗
PubMed1997

Successful treatment of established relapsing experimental autoimmune encephalomyelitis in mice with a monoclonal natural autoantibody.

We postulated that humoral autoimmunity can play a beneficial role in CNS demyelinating diseases such as multiple sclerosis. We previously demonstrated that monoclonal natural autoantibody SCH94.03 suppresses CNS inflammation and promotes remyelination in a virus-induced model of chronic progressive multiple sclerosis. To further investigate the relationship between natural autoimmunity and CNS demyelination, we examined the effect of SCH94.03 treatment on clinical relapses and pathological disease in SJL/J mice with established adoptive-transfer relapsing experimental autoimmune encephalomyelitis. Treatment with SCH94.03 after recovery from the initial episode of clinical disease reduced relapse rates by half, prolonged relapse onset by 6 days and reduced spinal cord demyelination and meningeal inflammation by 40%. These results are consistent with the hypothesized immunomodulatory function of natural autoantibodies, and are the first direct demonstration that natural humoral autoimmunity can be beneficial in an autoimmune T-cell-mediated CNS demyelinating disease.

Animals↗
PubMed1997

Intracellular signals coupled to different rat ileal muscarinic receptor subtypes.

Taking into account that the activation of different subtypes of ileal muscarinic acetylcholine receptors (mAChR) regulate gut functions such as tone, motility, and electrolyte secretion, we characterized the expression of mAChR in ileal-purified membranes. We also studied intracellular signals triggered by mAChR activation. Binding parameters obtained from saturation assays with the nonselective tritiated muscarinic antagonist, quinuclidynil benzilate ([3H]-QNB), were maximal number of binding sites (Bmax): 30 +/- 2 fmol/mg prot and dissociation constant (Kd): 0.2 +/- 0.03 nM. The competitive inhibition of [3H]-QNB specific binding by various nonlabelled muscarinic antagonists was measured and the rank order of potency was: atropine (ATROP) > 4-DAMP > AF-DX 116 > pirenzepine (PZ). The activation of mAChR by carbachol (CARB) increased ileal motility in a concentration-dependent manner (EC50 2 x 10[-7] M). The antagonists' order of potency to displace dose-response curve of CARB was: ATROP > 4-DAMP > AF-DX116 > PZ. Optimal concentration of CARB on ileal strips increased phosphoinositide turnover and cGMP levels by activating ml receptor subtype and decreased isoproterenol (ISO) stimulated levels of cAMP due to M2 receptor activation. We can conclude that the activation of different mAchR subtypes triggers different intracellular signals that could regulate intestinal tone and motility.

Animals↗
PubMed1997

Effects of transforming growth factor-beta and platelet-derived growth factor on oligodendrocyte precursors: insights gained from a neuronal cell line.

Conditioned medium derived from a rat central nervous system neuronal cell line B104 (B104 CM) was shown previously to contain uncharacterized potent mitogen(s) for oligodendrocyte/type-2 astrocyte (O-2A) progenitor cells. In this study, we demonstrated that B104 cells produce and secrete platelet-derived growth factor (PDGF)-AA homodimer, but not PDGF-B chain. B104 cells did not express other known potent mitogens for O-2A progenitor cells, including fibroblast growth factor-2 and neurotrophin-3. Unexpectedly, B104 cells also expressed transcripts of transforming growth factor-beta1 (TGF-beta1) and -beta2 (TGF-beta2), which are known to regulate O-2A progenitor cell differentiation and proliferation, and secreted exclusively the 25-kDa active forms of TGF-beta1 and TGF-beta2. Neutralization of B104 CM with anti-PDGF-AA antibody decreased proliferation of O-2A progenitor cells, whereas neutralization with anti-TGF-beta antibodies had no effect. The combination of PDGF and TGF-beta on proliferation was not equivalent to the effect of B104 CM, indicating the possibility of an unidentified growth factor. B104 CM maintained a high expression of PDGF-alpha receptor in oligodendrocytes. The observation that both a stimulatory factor (PDGF-AA) and a regulatory factor (TGF-beta) for O-2A progenitor cell proliferation and differentiation are produced from a single neuronal cell line emphasizes the potential critical interaction between neurons and O-2A progenitor cells in myelination and possibly in remyelination.

Animals↗