PubMed Health⌕ Search

Biomedical subjects

M Rodriguez

Publications and source records attributed to M Rodriguez.

At least 199 records · Page 11Linked to original sources
PubMed1999

Changes in the pattern of visceral protein concentrations after internal biliary drainage in patients with obstructive jaundice.

OBJECTIVE: To evaluate the influence of internal drainage on status of nutritional markers in patients with obstructive jaundice. DESSING: Prospective longitudinal study. SETTING: University hospital, Spain. SUBJECTS: 39 patients with obstructive jaundice (18 benign and 21 malignant obstructions). INTERVENTIONS: Nutritional state was assessed before and 10 days after endoscopic drainage. MAIN OUTCOME MEASURES: One anthropometric (body weight <95% of ideal) and two biochemical (albumin <35 g/L and prealbumin < 170 mg/L) as an indication of protein calorie malnutrition. Retinol binding protein and transferrin concentrations, total lymphocyte count, and nutritional prognostic index (NPI) were also measured. RESULTS: Thirty patients (77%) had protein calorie malnutrition. After internal drainage, 6 patients with benign obstruction and 11 with malignant tumours remained malnourished. No anthropometric variables or concentrations of proteins with long half-lives were affected by drainage. However, prealbumin (p < 0.01) and transferrin (p < 0.01) concentrations, and total lymphocyte count (p < 0.001) increased significantly in both groups. NPI also improved significantly after drainage from 43 (9) compared with 37 (5) in benign obstructions (p < 0.05) and 58.7 (14) compared with 52 (12) in malignant (p < 0.05), although in the latter group the mean nutritional risk index remained high. CONCLUSIONS: Concentrations of some of the visceral proteins studied (prealbumin and transferrin) improved 10 days after internal biliary drainage for both benign and malignant obstruction. However, many patients with malignant tumours remained malnourished with a high nutritional risk index.

Aged↗
PubMed1999

A quantitative analysis of oligodendrocytes in multiple sclerosis lesions. A study of 113 cases.

We studied quantitatively the fate of oligodendrocytes (OGs) during lesion formation in 395 lesion areas from biopsy and autopsy tissue of 113 multiple sclerosis cases. The density of OGs in multiple sclerosis lesions was variable at all stages of demyelinating activity, ranging from nearly complete loss to values exceeding those in the periplaque white matter (range 0-970 OGs/mm2) determine whether there were distinct patterns of OG pathology in different patients, we restricted our analysis to the 56 cases in which the longitudinal extent of the lesion extended from periplaque white matter into the active demyelinating edge and inactive plaque centre. Two major groups of OG pathology were defined by the presence or absence of increased OGs within the lesion. In 70% (39 out of 56) of the cases, OGs were variably reduced during active stages of myelin destruction, but reappeared within inactive or remyelinating areas. In inactive areas, an increased number of OGs expressing proteolipid protein (PLP) mRNA compared with those expressing myelin oligodendrocyte glycoprotein (MOG) suggested these cells may have been derived from the progenitor pool. In the remaining 30% (17 out of 56) of the cases, extensive destruction of myelinating cells at active sites of demyelination was observed, but OGs were absent in inactive plaque areas without remyelination. In all lesions from a given patient the pattern of OG pathology remained consistent. A highly significant negative correlation was observed between number of macrophages in lesions and number of MOG- and PLP mRNA-labelled OGs (MOG: r = -0.32, P < 0.0000118; PLP mRNA: r = -0.23, P < 0.00238). OG density did not correlate with T-cell and plasma cell inflammation, or axonal loss. The profound heterogeneity in extent and topography of OG destruction in active demyelinating lesions suggests that in subsets of multiple sclerosis patients, myelin, mature OGs and possibly OG progenitors are differentially affected.

Adult↗
PubMed1999

Absence of spontaneous central nervous system remyelination in class II-deficient mice infected with Theiler's virus.

We previously showed that Theiler's murine encephalomyelitis virus (TMEV)-infected major histocompatibility complex (MHC) class II-deficient mice develop both demyelination and neurologic deficits, whereas MHC class I-deficient mice develop demyelination but no neurologic deficits. The absence of neurologic deficits in the class I-deficient mice was associated with preserved sodium channel densities in demyelinated lesions, a relative preservation of axons, and extensive spontaneous remyelination. In this study, we investigated whether TMEV-infected class II-deficient mice, which have an identical genetic background (C57BL/6 x 129) as the class I-deficient mice, have preserved axons and spontaneous myelin repair following chronic TMEV-infection. Both class I- and class II-deficient mice showed similar extents of demyelination of the spinal cord white matter 4 months after TMEV infection. However, the class I-deficient mice demonstrated remyelination by oligodendrocytes, whereas class II-deficient mice showed minimal if any myelin repair. Demyelinated lesions, characterized by inflammatory infiltrates in both mutants, revealed disruption of axons in class II- but not class I-deficient mice. Further characterization revealed that even though class II-deficient mice lacked TMEV-specific IgG, they had virus-specific IgM, which, however, did not neutralize TMEV in vitro. In addition, class II-deficient mice developed TMEV-specific cytotoxic T-lymphocytes in the CNS during the acute (7 days) disease, but these cytotoxic lymphocytes were not present in the chronic stage of disease, despite a high titer of infectious virus throughout the disease. We envision that the presence of demyelination, high virus titer, absence of remyelination, and axonal disruption in chronically infected class II-deficient mice contributes to the development of paralytic disease.

Acute Disease↗
PubMed1999

CNS cell populations are protected from virus-induced pathology by distinct arms of the immune system.

The basis for the distinct patterns of brain pathology in individuals experiencing virus-induced encephalitis may be related to either the tropism of the virus or the host's response to virus infection of the central nervous system (CNS). In these studies we used Theiler's murine encephalomyelitis virus (TMEV) and a series of mice deficient in various immune system components (alpha/beta T cells, antibody, Class I MHC, and Class II MHC) to examine the hypothesis that discrete populations of CNS cells are protected differentially from virus infection by distinct arms of the immune response. Here we demonstrate that the Class I-mediated immune response provided more protection from areas of the brain (brainstem, corpus callosum and cerebellum) with abundant white matter as there was significantly more disease in these areas in beta2m -/- (Class I-deficient) mice as compared to A beta(0) (Class II-deficient) mice. In contrast, the striatum, with an abundance of neurons, was protected from virus-induced pathology primarily by antibody. In addition, we determined that antibody and alpha/beta T cells provided protection from severe deficits and death during the acute phase of the disease. The data presented here support the hypothesis that distinct immune system components function to protect discrete areas of the CNS from virus-induced pathology.

Animals↗
PubMed1999

Phage-displayed T-cell epitope grafted into immunoglobulin heavy-chain complementarity-determining regions: an effective vaccine design tested in murine cysticercosis.

A new type of immunogenic molecule was engineered by replacing all three complementarity-determining-region (CDR) loops of the human immunoglobulin (Ig) heavy-chain variable (V(H)) domain with the Taenia crassiceps epitope PT1 (PPPVDYLYQT) and by displaying this construct on the surfaces of M13 bacteriophage. When BALB/c mice were immunized with such phage particles (PIgphage), a strong protection against challenge infection in very susceptible female hosts was obtained. When specifically stimulated, the in vivo-primed CD4(+) and CD8(+) T cells isolated from mice immunized with PT1, both as a free peptide and as the PIgphage construct, proliferated in vitro, indicating efficient epitope presentation by both major histocompatibility complex class II and class I molecules in the specifically antigen-pulsed macrophages used as antigen-presenting cells. These data demonstrate the immunogenic potential of recombinant phage particles displaying CDR epitope-grafted Ig V(H) domains and establish an alternative approach to the design of an effective subunit vaccine for prevention of cysticercosis. The key advantage of this type of immunogen is that no adjuvant is required for its application. The proposed strategy for immunogen construction is potentially suitable for use in any host-pathogen interaction.

Animals↗
PubMed1999

Differential influence of interleukin-12 in the pathogenesis of autoimmune and virus-induced central nervous system demyelination.

Experimental allergic encephalomyelitis (EAE) and Theiler's murine encephalomyelitis virus (TMEV) disease are two demyelinating diseases of the central nervous system (CNS) that serve as animal models for multiple sclerosis. Th1 cells are thought to play a role in the pathogenesis of CNS demyelination in both these diseases. We show here the differential influence of interleukin 12, a critical cytokine for the development of Th1 cells in EAE and TMEV disease.

Animals↗
PubMed1999

Prevalent class I-restricted T-cell response to the Theiler's virus epitope Db:VP2121-130 in the absence of endogenous CD4 help, tumor necrosis factor alpha, gamma interferon, perforin, or costimulation through CD28.

C57BL/6 mice mount a cytotoxic T-lymphocyte (CTL) response against the Daniel's strain of Theiler's murine encephalomyelitis virus (TMEV) 7 days after infection and do not develop persistent infection or the demyelinating syndrome similar to multiple sclerosis seen in susceptible mice. The TMEV capsid peptide VP2121-130 sensitizes H-2Db+ target cells for killing by central-nervous-system-infiltrating lymphocytes (CNS-ILs) isolated from C57BL/6 mice infected intracranially. Db:VP2121-130 peptide tetramers were used to stain CD8(+) CNS-ILs, revealing that 50 to 63% of these cells bear receptors specific for VP2121-130 presented in the context of Db. No T cells bearing this specificity were found in the cervical lymph nodes or spleens of TMEV-infected mice. H-2(b) mice lacking CD4, class II, gamma interferon, or CD28 expression are susceptible to persistent virus infection but surprisingly still generate high frequencies of CD8(+), Db:VP2121-130-specific T cells. However, CD4-negative mice generate a lower frequency of Db:VP2121-130-specific T cells than do class II negative or normal H-2(b) animals. Resistant tumor necrosis factor alpha receptor I knockout mice also generate a high frequency of CD8(+) CNS-ILs specific for Db:VP2121-130. Furthermore, normally susceptible FVB mice that express a Db transgene generate Db:VP2121-130-specific CD8(+) CNS-ILs at a frequency similar to that of C57BL/6 mice. These results demonstrate that VP2121-130 presented in the context of Db is an immunodominant epitope in TMEV infection and that the frequency of the VP2121-130-specific CTLs appears to be independent of several key inflammatory mediators and genetic background but is regulated in part by the expression of CD4.

Animals↗
PubMed1999

Feeding difficulties and foregut dysmotility in Noonan's syndrome.

PURPOSE: Noonan's syndrome is a common dysmorphic syndrome in which failure to thrive and gastrointestinal symptoms are frequent but poorly understood. DESIGN: Twenty five children with Noonan's syndrome were investigated by contrast radiology, pH monitoring, surface electrogastrography (EGG), and antroduodenal manometry (ADM). RESULTS: Sixteen had poor feeding and symptoms of gastrointestinal dysfunction. All 16 required tube feeding. Seven of 25 had symptoms of foregut dysmotility and gastro-oesophageal reflux. In the most symptomatic children (four of seven) EGG showed fasting frequency gradient loss along the stomach fundus and pylorus with antral postprandial frequency loss. ADM showed shortened fasting cycle length, with abnormal phase III and shortened postprandial activity containing phasic contractions. IMPLICATIONS: Gastroduodenal motor activity was reminiscent of 32-35 week preterm patterns. The feeding difficulties appear to resolve as gut motility matures. In Noonan's syndrome, feeding problems appear to be the result of delayed gastrointestinal motor development.

Barium Sulfate↗
PubMed1999

Positron emission tomography for evaluating para-aortic nodal metastasis in locally advanced cervical cancer before surgical staging: a surgicopathologic study.

PURPOSE: Positron emission tomographic (PET) scanning provides a novel means of imaging malignancies. This prospective study was undertaken to evaluate PET scanning in detecting para-aortic nodal metastasis in patients with locally advanced cervical carcinoma and no evidence of extrapelvic disease before planned surgical staging lymphadenectomy. MATERIALS AND METHODS: After 20 mCi of 2-[18F]fluoro-2-deoxy-D-glucose (FDG) were administered intravenously, the abdomen and pelvis were scanned. Continuous bladder irrigation was used to reduce artifact. Patients were classified by the presence or absence of FDG uptake in the primary tumor and in pelvic or para-aortic nodes. Para-aortic node metastases were classified as present or absent according to a standardized staging procedure. Pelvic node metastases were similarly classified in a subset of patients who underwent pelvic node resection. RESULTS: Thirty-two patients with stage IIB (n = 6), IIIB (n = 24), and IVA (n = 2) tumors were studied. Fluorodeoxyglucose was taken up by 91% of the cervical tumors. Six of eight patients with positive para-aortic node metastasis had PET scan evidence of para-aortic nodal metastasis. One of the two false-negatives had only one microscopic focus of metastatic cancer. In the para-aortic nodes, PET scanning had a sensitivity of 75%, a specificity of 92%, a positive predictive value of 75%, and a negative predictive value of 92%. Fluorodeoxyglucose para-aortic nodal uptake conferred a relative risk of 9.0 (95% confidence interval, 2.3 to 36.0) for para-aortic nodal metastasis. All 10 of 17 patients with metastasis were predicted by PET scanning (P < .001); five of these patients had abnormalities on computed tomographic scans. CONCLUSION: Cervical cancers have a high avidity for FDG. The use of PET-FDG scanning accurately predicts both the presence and absence of pelvic and para-aortic nodal metastatic disease.

Aorta↗
PubMed1999

Effect of phosphate on parathyroid hormone secretion in vivo.

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

Animals↗
PubMed1999

Literacy promotion for Hispanic families in a primary care setting: a randomized, controlled trial.

BACKGROUND: Reading aloud is an important activity to prepare children to succeed in learning to read. Many Hispanic children have reading difficulties and therefore are at increased risk for school failure. METHODS: We conducted a prospective, randomized, controlled study to evaluate the effectiveness of a literacy promoting intervention delivered to low-income Hispanic families with infants. We consecutively enrolled 135 low-income Hispanic parents of healthy 5 to 11 month old infants. Families were randomly assigned to an intervention (n = 65) or control (n = 70) group. At enrollment and at two consecutive well-child visits, pediatricians gave intervention families: 1) an age-appropriate bilingual children's book, 2) a bilingual handout explaining the benefits of reading to children, and 3) literacy-promoting anticipatory guidance. Ten months after enrollment we reinterviewed 130 parents. RESULTS: Both groups were comparable at baseline. At follow-up, intervention parents were more likely to read books with their child at least 3 days/week (intervention = 66% vs control parents = 24%) and to report that reading books was one of their three most favorite things to do with their child (intervention = 43% vs controls = 13%). Intervention families also had a greater number of children's books and total books at home. Using a multiple logistic regression model, controlling for child and parental age, reading habits, and English proficiency, we found that the odds of parents reading to their child at least 3 days/week were 10 times greater in intervention families (OR 10.1, 95% CI 4.0-25.6) compared with control families. CONCLUSIONS: This simple, culturally appropriate intervention significantly increased literacy behaviors in low-income Hispanic families.

Adult↗
PubMed1999

CT in malignancy grading and prognostic prediction of non-Hodgkin's lymphoma.

PURPOSE: The presence of tumor inhomogeneities in MR images of non-Hodgkin's lymphoma (NHL) provides information about malignancy grade and prognosis. The aim of this study was to determine whether CT images are also informative in these respects. MATERIAL AND METHODS: Sixty-three CT examinations in patients with NHL (32 high-grade and 31 low-grade tumors) were reviewed retrospectively by two senior radiologists. The tumor patterns were classified subjectively as homogeneous, slightly inhomogeneous or severely inhomogeneous and their relations to malignancy grade, clinical characteristics and prognosis were determined. RESULTS: Sixteen out of 17 patients with a severely inhomogeneous tumor pattern had high-grade NHL tumors while 21 out of 29 patients with a homogeneous tumor appearance had low-grade NHL tumors. Among chemotherapy-treated patients, those with the highest degree of inhomogeneity had a significantly worse prognosis (9 out of 11 patients died). This relationship was not found in patients treated with radiotherapy. CONCLUSION: A severely inhomogeneous tumor pattern on CT images was found to be associated with a high malignancy grade in NHL. This CT pattern was also compatible with a poor prognosis in patients treated with chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1998

Differentiation-specific mRNA expression of a mouse bipotential glial cell line.

We have previously reported that a bipotential glial cell line from mouse cerebrum, designated OS3, phenotypically differentiates into oligodendrocytes and astrocytes both in vitro and in vivo. To study the potential mechanisms of differentiation, in this study we investigated mRNA expression of cytokines and developmentally regulated proteins in OS3 during differentiation into oligodendrocytes by semi-quantitative reverse transcription and polymerase chain reaction. In the presence of 10% calf serum OS3 cells expressed IL-1alpha and IL-1beta mRNA. However, when the cells were cultured in chemically defined medium or low serum-containing medium the expression of IL-1alpha and IL-1beta mRNA was down-regulated. Under stimulation of phorbol ester, expression of IL-6 and nerve growth factor mRNA was up-regulated. The capacity for differentiation of OS3 cells into oligodendrocytes in vitro was limited and most OS3 cells ceased their differentiation at the proligodendroblast stage. However, expression of proteolipid protein (PLP) and DM20 mRNA was detectable and was up-regulated in accordance with the differentiation into oligodendrocytes. As a control, primary astrocytes expressed DM20 mRNA but not PLP mRNA and the expression of DM20 mRNA was independent of culture condition. Therefore, OS3 cells will be of use for the study of differentiation of progenitor cells into type-2 astrocytes or oligodendrocytes at the molecular level.

Animals↗
PubMed1998

Targeting of IgMkappa antibodies to oligodendrocytes promotes CNS remyelination.

We previously identified the remyelinating activity of a natural IgMkappa oligodendrocyte-reactive autoantibody (SCH94.03), using a virus-induced murine model of multiple sclerosis. We now describe a second mouse IgMkappa monoclonal antibody (mAb) (SCH79.08) raised against normal mouse spinal cord homogenate, which reacts with myelin basic protein and also promotes remyelination. Because these two mAbs recognize different oligodendrocyte antigens, several previously identified oligodendrocyte-reactive IgMkappa mAbs (O1, O4, A2B5, and HNK-1), each with distinct antigen specificities, were evaluated and found to promote remyelination. In contrast, IgMkappa mAbs that did not bind to oligodendrocytes showed no remyelination. One of these, CH12 IgMkappa mAb, which shares variable region cDNA sequences with SCH94.03 except for amino acid differences in the complementarity-determining region 3 in both heavy and light chains, did not bind to oligodendrocytes and did not promote remyelination. The fact that multiple oligodendrocyte-reactive antibodies with distinct antigen reactivities induce remyelination argues against direct activation by a unique cell surface receptor. These findings are most consistent with the hypothesis that the binding of mAbs to oligodendrocytes in the lesions induces myelin repair via indirect immune effector mechanisms initiated by the mu-chain. Importantly, these studies indicate that oligodendrocyte-reactive natural autoantibodies may provide a powerful and novel therapeutic means to induce remyelination in multiple sclerosis patients.

Animals↗
PubMed1998

NPY receptor subtypes involved in the contraction of the proximal colon of the rat.

Experiments were designed to determine the receptor subtype(s) involved in the contraction of the rat proximal colon to NPY. In this tissue, mRNA of Y2 and Y4 NPY receptor subtypes were highly expressed, whereas Y5 mRNA levels were very low and Y1 mRNA levels were intermediate. NPY analogues induced contractions with the following order of potency: rPP > hPP = PYY = NPY = [Leu31,Pro34]NPY > NPY(2-36) = [D-Trp32]NPY > NPY(33-36). Responses to NPY, PYY and NPY(13-36) were not or partially affected by tetrodotoxin, in contrast to the responses to [Leu31,Pro34]NPY, rPP, hPP and [D-Trp32]NPY which were fully blocked. Atropine did not inhibit the contractions to NPY, PYY and [Leu31,Pro34]NPY but significantly affected those to NPY(13-36), [D-Trp32]NPY, rPP and hPP. The specific Y1 receptor antagonist BIBP 3226 was ineffective but JCF 104 and JCF 105 (two compounds with preferential affinity toward the hY5 receptor versus the hY1 or hY2 receptor) abolished the contractions provoked by the NPY analogues. These results suggest that NPY activates three receptor subtypes, a Y2 subtype possibly by a direct action on the smooth muscle cells, as well as a Y4 and a Y5 (or 'Y5-like') subtype which, respectively, release acetylcholine and an unknown neurotransmitter.

Animals↗
PubMed1998

Perforin-dependent neurologic injury in a viral model of multiple sclerosis.

In this study we demonstrate perforin-mediated cytotoxic effector function is necessary for viral clearance and may directly contribute to the development of neurologic deficits after demyelination in the Theiler's murine encephalomyelitis virus (TMEV) model of multiple sclerosis. We previously demonstrated major histocompatability complex (MHC) class I-deficient (beta2m-deficient) mice with an otherwise resistant genotype develop severe demyelination with minimal neurologic disease when chronically infected with TMEV. These studies implicate CD8(+) T cells as the pathogenic cell in the induction of neurologic disease after demyelination. To determine which effector mechanisms of CD8(+) T cells, granule exocytosis or Fas ligand expression, play a role in the development of demyelination and clinical disease, we infected perforin-deficient, lpr (Fas mutation), and gld (Fas ligand mutation) mice with TMEV. Perforin-deficient mice showed viral persistence in the CNS, chronic brain pathology, and demyelination in the spinal cord white matter. Perforin-deficient mice demonstrated severely impaired MHC class I-restricted cytotoxicity against viral epitopes, but normal MHC class II-restricted delayed-type hypersensitivity responses to virus antigen. Despite demyelination, virus-infected perforin-deficient mice showed only minimal neurologic deficits as indicated by clinical disease score, activity monitoring, and footprint analysis. Perforin- and MHC class II-deficient mice (with functional CD8(+) T cells and perforin molecules and an H-2(b) haplotype) had comparable demyelination and genotype, however, only the latter showed severe clinical disease. Gld and lpr mice demonstrated normal TMEV-specific cytotoxicity and maintained resistance to TMEV-induced demyelinating disease. These studies implicate perforin release by CD8(+) T cells as a potential mechanism by which neurologic deficits are induced after demyelination.

Animals↗