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M Rodriguez

Publications and source records attributed to M Rodriguez.

At least 361 records · Page 20Linked to original sources
PubMed1995

Predicting malignancy grade with PET in non-Hodgkin's lymphoma.

UNLABELLED: Our goal was to determine whether PET with 11C-methionine and/or 18FDG could predict malignancy grade in non-Hodgkin's lymphoma (NHL). METHODS: Twenty-three patients with high-grade, low-grade or transformed low-grade NHL were investigated. Standardized uptake values (SUV), transport rate and mass influx values were calculated both for the whole tumor [mean regions of interest, (ROI)] and for the tumor area with the highest levels of activity, comprising four contiguous pixels within each tumor and designated as a hot spot. RESULTS: Both 11C-methionine and 18FDG detected all tumors. In addition, 18FDG discriminated between high- and low-grade NHL, whereas 11C-methionine did not. With 18FDG, three transformed low-grade NHLs behaved in an intermediate manner. All quantitative uptake values correlated well with each other for both tracers, except for the mean ROI SUV and transport rate of 11C-methionine. Quantifications of mean ROI uptake and hot spots were strongly correlated. CONCLUSION: The results of this study together with previous findings from other studies indicate that 18FDG but not 11C-methionine can predict malignancy grade in NHL. Further studies with a larger series of patients are needed.

Adult↗
PubMed1995

High-dose chemotherapy with BEAC regimen and autologous bone marrow transplantation for intermediate grade and immunoblastic lymphoma: durable complete remissions, but a high rate of regimen-related toxicity.

Forty-eight adult patients with recurrent or refractory intermediate grade or immunoblastic lymphoma received high-dose carmustine (BCNU), etoposide, Ara C and cyclophosphamide (BEAC), followed by autologous bone marrow transplantation (BMT). Median follow-up is 906 days (range 613-2067 days). The complete remission rate was 42% and 22% had a partial response. Actuarial failure-free survival is 30% +/- 6.6%. Twenty one patients relapsed or progressed. Only one relapse occurred > 1 year after autologous BMT. Adverse prognostic factors for failure-free survival include high LDH at the time of autologous BMT, chemotherapy-refractory disease and multiple prior relapses. Patients with chemotherapy responsive first salvage (those achieving first CR only with salvage chemotherapy and those with first relapse, responding to salvage chemotherapy) had a failure-free survival of 52% +/- 10% vs 12% +/- 6% for those with more advanced disease. Of 13 patients who had no adverse factors, only two relapsed. Treatment-related mortality occurred in 23%, including infection (n = 4), cardiac toxicity (n = 4), pulmonary toxicity (n = 2) and hemorrhage (n = 1). Pulmonary toxicity was more common among patients who had received prior radiation-therapy to the chest. BEAC chemotherapy with autologous BMT is an effective but relatively toxic regimen for patients with relapsed or refractory lymphomas. The combination of chemotherapy-responsive disease after failure of one chemotherapy regimen and normal LDH identifies patients with a favorable prognosis. Alternative cytotoxic regimens require evaluation, with the goal of reducing treatment related mortality. More effective cytoreductive therapy is required for patient with poor prognostic features.

Adolescent↗
PubMed1995

Hyperstimulation of leukocytes by plasma from cardiopulmonary by-pass patients is diminished by morphine and IL-10 pretreatment.

OBJECTIVE: The trauma of cardiopulmonary by-pass (CPB) in cardiac surgery results in a whole body diffuse inflammatory response characterized in part by hyperstimulation of leukocytes. Partially this is due to an increase in the release of biological response modifiers such as cytokines, as noted by the immunocyte stimulatory actions of cell-free plasma obtained postoperatively from CPB patients. The present study was conducted to determine whether CPB plasma induced immunocyte hyperstimulation can be prevented with naturally occurring immune inhibitory substances, specifically, interleukin (IL)-10 and/or morphine. EXPERIMENTAL DESIGN: Controlled in vitro study of the application of drugs to naive immunocytes to block the exitation caused by CPB-plasma. SETTING: University-based tertiary care hospital. PATIENTS: Plasma was obtained from ten patients undergoing CPB. Eligibility included admission for elective cardiac surgery, which no chronic illnesses or acute processes. INTERVENTIONS: Monocytes and granulocytes were pretreated with IL-10 and/or morphine before exposure to plasma obtained from patients undergoing CPB, as CPB-plasma would stimulate naive monocytes and granulocytes in a manner similar to that previously reported in CPB-patients. MEASURES: Computer-assisted microscopic image analysis, measuring cellular conformational and velocity changes, was used to evaluate the effect of treatment on the immunocytes response to stimulation with CPB-plasma. RESULTS: Pretreatment of cells with IL-10 and/or morphine significantly diminished the hyperstimulation induced by CPB-plasma in a concentration-dependent manner. In contrast, when the cells were initially or simultaneously exposed to CPB-plasma, IL-10 and/or morphine had no effect.

Anesthesia↗
PubMed1995

Effect of calcitriol replacement on serum calcitonin and parathyroid hormone levels in CAPD patients.

Calcitonin-secreting cells, 'C cells', have specific receptors for calcitriol, thus the calcitriol deficiency in uraemia may affect calcitonin secretion and/or production. The aim of the present study was to evaluate in CAPD patients the effect of calcitriol replacement (4 weeks of oral calcitriol, 0.5 micrograms/day) on both, basal calcitonin concentration and calcitonin response to calcium infusion (calcium gluconate, 3 mg/kg/h). Calcitriol replacement produced a normalization of serum calcitriol level without a significant change in serum calcium concentration. After calcitriol replacement, basal calcitonin increased from 78 +/- 15 to 101 +/- 13 pg/ml, P < 0.05. The increment in calcitonin induced by a calcium infusion was lower after (15 +/- 4 pg/ml) than before (29 +/- 4 pg/ml) calcitriol replacement. In addition, calcitriol administration induced a decrease in serum PTH level. Replacement of calcitriol in CAPD patients produced an increase in serum calcitonin concentration and a decrease in the calcitonin response to hypercalcaemia.

Administration, Oral↗
PubMed1995

The effect of cyclosporine and methylprednisolone on plasma lipoprotein levels in rats.

The aim of this study was to evaluate in rats the effects of cyclosporine, methylprednisolone, and the combination of both (CyP) on plasma lipids and lipoproteins levels. Three groups received a low doses of cyclosporine, methylprednisolone, and CyP (cyclosporine, 15 mg/kg/day; methylprednisolone, 1 mg/kg/day; and CyP, 15 plus 1 mg/kg/day of cyclosporine and methylprednisolone, respectively). Three additional groups received high doses (cyclosporine, 30 mg/kg/day; methylprednisolone, 2 mg/kg/day; and CyP, 30 plus 2 mg/kg/day of cyclosporine and methyprednisolone, respectively). The administration of cyclosporine produced an increase in plasma levels of triglycerides, very low density lipoprotein (VLDL) triglycerides, low-density lipoprotein (LDL) cholesterol and in total cholesterol/HDL cholesterol and LDL cholesterol/high-density lipoprotein (HDL) cholesterol ratios. In addition, cyclosporine decreased plasma HDL cholesterol and HDL2 cholesterol levels. The administration of methylprednisolone produced an increase in triglycerides and VLDL triglycerides and a decrease in HDL cholesterol and HDL2 cholesterol levels. Total cholesterol/HDL cholesterol and LDL cholesterol/HDL cholesterol ratios did not change after administration of methylprednisolone. The association of both drugs resulted in a greater increase in triglycerides and VLDL triglycerides than the separated administration of either cyclosporine or methylprednisolone alone. In rats receiving cyclosporine the increase in triglycerides and VLDL triglycerides may be due to a significant decrease in plasma lipoprotein lipase activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Spontaneous CNS remyelination in beta 2 microglobulin-deficient mice following virus-induced demyelination.

Animal models with selective genetic immunodeficiencies are useful tools to identify pathogenic mechanisms of disease. Resistant (C57BL/6F 129/J) (H-2b) mice are rendered susceptible to Theiler's murine encephalomyelitis virus-induced demyelination by genetic disruption of the beta 2 microglobulin gene [beta 2 m(-l-)]. The absence of beta 2 m prevents the expression of major histocompatibility complex class I molecules and normal levels of functional CD8+ T cells. We tested whether genetic depletion of beta 2 m would permit CNS remyelination after chronic demyelination induced by the Daniel's strain of Theiler's virus. In contrast to the minimal spontaneous remyelination observed in SJL/J mice after infection with the Daniel's strain of Theiler's virus, chronically infected beta 2 m(-I-) mice showed extensive and progressive spontaneous CNS remyelination at 6, 12, and 18 months after infection. Spontaneous remyelination by both oligodendrocytes and Schwann cells occurred despite the presence of persistent virus antigen and RNA, but was associated with diminished virus-specific humoral and delayed-type hypersensitivity responses. These experiments support the hypothesis that the immune response inhibits myelin regeneration after virus-induced CNS demyelination.

Animals↗
PubMed1994

Peptide inhibitors of src SH3-SH2-phosphoprotein interactions.

Activated pp60c-src has been implicated in a number of human malignancies including colon carcinoma and breast adenocarcinoma. Association of the src SH2 domain with tyrosine-phosphorylated proteins plays a role in src-mediated signal transduction. Inhibitors of src SH2 domain-phosphoprotein interactions are, thus, of great interest in defining the role(s) of src in signal transduction pathways. To facilitate such studies, an enzyme-linked immunosorbent assay (ELISA) was developed to detect inhibitors of src SH2-phosphoprotein interactions. This assay measures inhibition of binding of a fusion construct (glutathione S-transferase src SH3-SH2) with autophosphorylated epidermal growth factor receptor tyrosine kinase domain. Activities of phosphopeptide segments derived from potential src SH2 cognate phosphoprotein partners were determined, with the focal adhesion kinase-derived segment VSETDDY*AEIIDE yielding the highest inhibitory activity. Structure activity studies starting from acetyl (Ac)-Y*EEIE have identified Ac-Y*Y*Y*IE as the most active compound screened in the ELISA. This compound is at least 20-fold more active than the parent peptide Ac-Y*EEIE. A high resolution (2 A) crystal structure of human src SH2 complexed with Ac-Y*EEIE was obtained and provided a useful framework for understanding the structure-activity relationships. Additionally, Ac-Y*EEIE was able to block interactions between src and its cellular phosphoprotein partners in vanadate-treated cell lysates from MDA-MB-468 breast carcinoma cells. However, it is unable to abrogate proliferation of MDA-MB-468 cells in culture, presumably because of poor cell penetration and/or lability of the phosphate group on tyrosine.

Amino Acid Sequence↗
PubMed1994

Aconitase is readily inactivated by peroxynitrite, but not by its precursor, nitric oxide.

Mitochondrial and cytosolic aconitases have been indicated as major targets of .NO- and O2-.-mediated toxicity in cells due to the oxidant-mediated disruption of the [4Fe-4S] prosthetic group. However, under circumstances in which both .NO and O2-. are generated, their almost diffusion-controlled combination reaction (k = 6.7 x 10(9) M-1 s-1), leading to the formation of peroxynitrite anion (ONOO-), can out-compete the direct reactions of .NO and O2-. with aconitase and even the enzymatic dismutation of O2-. by superoxide dismutase. In this work, we report that ONOO- reacts with isolated pig heart mitochondrial aconitase at 1.4 x 10(5) M-1 s-1, resulting in a significant loss of enzymatic activity. Aconitase activity was totally recovered after postincubation with thiols and ferrous iron, indicating that ONOO- reactions with the enzyme involve the perturbation of the labile Fe alpha to yield the inactive [3Fe-4S] cluster, which is also evident by spectral changes. On the other hand, anaerobic exposure of isolated aconitase to high concentrations of .NO (> 100 microM) led to a moderate inhibition of the enzyme, which could be fully overcome by .NO displacement under an argon-saturated atmosphere, in agreement with the formation of a reversible inhibitory complex between .NO and the active site of aconitase. Superoxide inactivated mitochondrial aconitase at (3.5 +/- 2) x 10(6) M-1 s-1, a reaction rate 3 orders of magnitude slower than its reaction rate with .NO. O2-. could represent the main mechanism of inactivation of the enzyme in systems in which it is formed without significant concomitant production of .NO. Our results imply that the mechanisms by which .NO and O2-. inactivate aconitase in cell systems may not be simple due to their direct reactions with the iron-sulfur cluster, but may rely on the formation of ONOO-.

Aconitate Hydratase↗
PubMed1994

Recombinant human IL-6 suppresses demyelination in a viral model of multiple sclerosis.

We used a murine model of multiple sclerosis (MS) induced by Theiler's murine encephalomyelitis virus (TMEV) to test the effect of IL-6 on central nervous system (CNS) demyelination. Administration of human rIL-6 (2.5 micrograms/dose), beginning one day before infection and then twice daily for 28 days, dramatically reduced demyelination and inflammation in the spinal cord of susceptible SJL/J mice. Benefit also was observed when rIL-6 was used as a therapeutic agent and begun on day 15 after infection, a time in which there is the first evidence of inflammation and demyelination in the spinal cord. Suppression of myelin damage by treatment with rIL-6 was associated with fewer virus Ag-positive cells in the spinal cord. Infectious CNS virus titers, as measured by plaque assay, were reduced in rIL-6-treated animals on day 15 after infection, but not on day 7, 22, or 29 after infection. Total serum Igs and virus-specific Igs, as detected by indirect ELISA, were increased markedly in rIL-6-treated mice, whereas no effect was observed on TMEV-neutralizing Ab titers. In vivo administration of rIL-6 inhibited a murine CNS-demyelinating disease induced by a virus, suggesting that this IL may have application for the treatment of human MS.

Animals↗
PubMed1994

Microglia in invertebrate ganglia.

The results of this study lend strong support to the concept of the existence in insects and molluscs of a distinctive class of neuroglial cells comparable to vertebrate microglia. The evidence presented is as valid as that used in reference to the separate status of vertebrate microglia--i.e., the demonstration of a close structural and functional relationship of these cells with cells of the immune system. As in vertebrates, the excision of ganglia from three invertebrate species (the molluscs Planorbarius corneus and Mytilus edulis and the insect Leucophaea maderae) and their maintenance in incubation media led to an exodus of small cells and their accumulation in the culture dish. During this process, they underwent conformational changes from stellate to rounded, and then to more or less ameboid, comparable to those indicative of the process of activation in the animals' immunocytes. Functional characteristics which these translocated microglia-like cells share with immunocytes are motility, phagocytotic activity, and adherence to the culture dish. Furthermore, the two cells have certain biochemical features in common--e.g., the presence of certain cytokines and (at least in Planorbarius) that of corticotropin. An additional phenomenon of particular interest for the classification of microglial elements is their response to morphine. At 10(-6) M, this drug decreases not only the number of cells emerging from the excised ganglia but also the degree of their transformation to the "active" ameboid form. This dose-dependent and naloxone-sensitive effect of morphine on microglial cells parallels that on activated immunocytes of the same species. Corresponding results demonstrating an inhibitory effect of morphine on mobilized microglial cells of the frog Rana pipiens indicate that this relationship between the two cell types under consideration also exists in vertebrates. Binding and displacement experiments with membrane homogenates of microglial cells as well as immunocytes of Mytilus have shown that the effects of morphine on both cell types are mediated by the same special opiate receptor (mu 3).

Animals↗
PubMed1994

Effects of gastrin on 3',5'-cyclic adenosine monophosphate, intracellular calcium, and phosphatidylinositol hydrolysis in human colon cancer cells.

Gastrin is a trophic factor for some human colon cancer cells. However, the signal-transduction pathways by which gastrin regulates growth are still unknown. We examined the effect of synthetic human gastrin-17 (G-17) on signal-transduction pathways and cell growth using 4 different human colon cancer cell lines (LoVo, COLO 320, HT-29, and HCT116). G-17 stimulated the production of cyclic AMP in LoVo, COLO 320, and HCT116 cells, while G-17 stimulated phosphatidylinositol hydrolysis and mobilization of intracellular calcium in HT-29 cells. The growth-regulatory effect of G-17 on these colon cancer cells (stimulatory on LoVo, COLO 320, and HT-29 cells; inhibitory on HCT116 cells) was well correlated with the effect of G-17 on the signal-transduction pathway in each cell line. We further examined the effect of a selective cholecystokinin-B type receptor antagonist, JMV 320, on G-17-induced signal-transduction pathways and G-17-regulated growth. In each cell line, the effect of JMV 320 on G-17-induced signal-transduction pathways was well correlated with that on G-17-regulated growth. G-17 appears to regulate, at least to some extent, growth of human colon cancer cells through gastrin receptor-linked signal-transduction pathways that are cell-specific.

Calcium↗
PubMed1994

National survey of ovarian carcinoma XII. Epithelial ovarian malignancies in women less than or equal to 25 years of age.

BACKGROUND: Epithelial ovarian carcinoma in women less than or equal to 25 years of age is a rare entity. This study used the database of the National Survey of Ovarian Carcinoma to analyze the disease and survival in women less than or equal to 25 years of age. METHODS: Tumor registries of 1230 hospitals were asked to enter the first 25 patients with histologically confirmed ovarian carcinoma from January 1 to December 31, 1983 and from January 1 to December 31, 1988. Data for a total of 12,136 patients were collected. Survival analysis and long-term evaluations were available on patients diagnosed with cancer in 1983. Chi-square analysis was used to compare the frequencies of operations performed in 1983 and 1988. RESULTS: Of 12,136 patients with epithelial ovarian carcinoma, 135 (1.1%) were less than or equal to 25 years of age. The majority of patients had early disease with the following distributions: stage I, 58.5%; stage II, 8.9%; stages III and IV, 28.9%. More patients had early-grade lesions with the following distributions: borderline, 21.5%; Grade 1, 27.4%; Grade 2, 11.1%; Grade 3, 6.7%; and unknown grade, 33.3%. Optimal cytoreduction was achieved in 77% of patients. During the 5-year study period, there was a significant change in the patterns of care toward more conservative surgery. In particular, unilateral salpingooophorectomy increased significantly from 38.2 to 59.7% (P = 0.0237), whereas hysterectomy decreased proportionally from 54.4 to 29.9% (P = 0.0039). The overall 5-year survival rate was 87.3% with the following divisions: stage I, 96.7%; stage II, 90.0%; stage III, 78.5%; and stage IV, 76.4%. Regarding histologic grade, 5-year survival rates were: borderline, 91.6%; Grade 1, 93.7%; Grade 2, 85.7%; Grade 3, 33.3%. CONCLUSION: Young patients with epithelial ovarian carcinoma appeared to have favorable stage and histologic grade. These factors combined with good performance status and optimal cytoreduction resulted in improved survival from cancer.

Adult↗
PubMed1994

[The value of silastic prostheses in Kienböck's disease].

Eight patients underwent silicon replacement arthroplasty for treatment of Kienböck's disease between 1980 and 1984. Seven patients were available for a clinical and radiological ten-year follow-up control. A three-stemmed arthrodesis by arthrosis was done on one patient. Subjective results were good, although a reduction of one third of the mobility and strength of the wrist was noticed. Erosive osteolysis, carpal instability, radiocarpal arthrosis and a 36% reduction of the initial height of the implants was seen on the X-rays. The lytic lesion represents a progressive silicone particle-wear synovitis which threatens the future of the carpus. Nowadays, this kind of arthroplasty no longer has its place in the treatment of Kienböck's disease.

Adolescent↗
PubMed1994

Involvement of pp60c-src with two major signaling pathways in human breast cancer.

The phosphotyrosine residues of receptor tyrosine kinases serve as unique binding sites for proteins involved in intracellular signaling, which contain SRC homology 2 (SH2) domains. Since overexpression or activation of the pp60c-src kinase has been reported in a number of human tumors, including primary human breast carcinomas, we examined the interactions of the SH2 and SH3 domains of human SRC with target proteins in human carcinoma cell lines. Glutathione S-transferase fusion proteins containing either the SH2, SH3, or the entire SH3/SH2 region of human SRC were used to affinity purify tyrosine-phosphorylated proteins from human breast carcinoma cell lines. We show here that in human breast carcinoma cell lines, the SRC SH2 domain binds to activated epidermal growth factor receptor (EGFR) and p185HER2/neu. SRC SH2 binding to EGFR was also observed in a nontumorigenic cell line after hormone stimulation. Endogenous pp60c-src was found to tightly associate with tyrosine-phosphorylated EGFR. Association of the SRC SH2 with the EGFR was blocked by tyrosyl phosphopeptides containing the sequences surrounding tyrosine-530, the regulatory site in the SRC C terminus, or sequences surrounding the major sites of autophosphorylation in the EGFR. These results raise the possibility that association of pp60c-src with these receptor tyrosine kinases is an integral part of the signaling events mediated by these receptors and may contribute to malignant transformation.

Amino Acid Sequence↗
PubMed1994

Calcitriol corrects deficient calcitonin secretion in the vitamin D-deficient elderly.

The thyroid calcitonin-producing C cells possess vitamin D receptors and synthesize the vitamin D-dependent calbindin D28K. The present study evaluates the possible direct or indirect influence of vitamin D on calcitonin secretion in the elderly. Serum calcitonin was measured before and after a short calcium infusion (1.5 mg/kg over 10 minutes) in nine normal young adults (30 +/- 4 years, mean +/- SEM) and eight elderly subjects (78 +/- 4 years). The test was repeated 48 h after the last of three intravenous injections of calcitriol (2 micrograms) given every other day. Basal serum calcium did not change, but basal calcitonin of the elderly increased from 7 +/- 1 to 10 +/- 1 pg/ml (p < 0.06), similar to basal values in young adults (11 +/- 1 pg/ml). The increase in calcitonin after calcium infusion increased from 8 +/- 1 to 14 +/- 1 pg/ml (p < 0.001) after calcitriol treatment and approached the increase in young adults (18 +/- 3 pg/ml). These data demonstrate that calcitriol can improve and nearly normalize the impaired calcitonin secretion of the mildly vitamin D-deficient elderly subjects without changes in serum calcium, whereas the inverse situation is observed for parathyroid hormone.

Adult↗
PubMed1994

Inhibition of mitochondrial electron transport by peroxynitrite.

Mammalian mitochondria are sensitive targets of the cytotoxic effects of superoxide (O.2-) and nitric oxide (.NO). In turn, when superoxide and nitric oxide are simultaneously produced, they rapidly react with each other yielding the highly oxidizing peroxynitrite anion (ONOO-) which may be also toxic to mammalian mitochondria. In this study we report that peroxynitrite exposure to rat heart mitochondria resulted in significant inactivation of electron carriers such as succinate dehydrogenase and NADH dehydrogenase as well as the mitochondrial ATPase. As a result of enzyme inactivation, peroxynitrite lead to a profound inhibition of glutamate/malate- and succinate-supported oxygen consumption but did not cause mitochondrial uncoupling. Secondary to inhibiting mitochondrial electron transport, peroxynitrite induced an enhanced succinate-stimulated hydrogen peroxide formation by heart mitochondria. Most of the damaging effects against mitochondria can be ascribed to peroxynitrite anion itself and not to hydroxyl radical-like oxidant yielded during the proton-catalyzed decomposition of peroxynitrite, as hydroxyl radical scavengers provided a rather modest protection. Our observations indicate that mitochondria may constitute a key intracellular loci for the toxic effects of peroxynitrite under the various pathological conditions in which peroxynitrite appears to play a contributory role.

Animals↗
PubMed1994

Analysis of sites of foot and mouth disease virus persistence in carrier cattle via the polymerase chain reaction.

This study was undertaken in order to explore possible sites of foot-and-mouth disease virus (FMDV) persistence during the carrier state. Tissue samples taken from experimentally infected animals at different times post-infection (p.i.) were examined by conventional viral isolation and the polymerase chain reaction (PCR) technique. The analysis of samples from several organs taken from 17 bovines between 3 and 270 days p.i. allowed the following conclusions: 1) Virus present in oesophageal-pharyngeal fluids (OPF) during the carrier state originates in the pharynx as shown by the detection of antisense FMDV RNA by PCR, 2) PCR is more sensitive than standard virus isolation techniques and may be used for the rapid detection of FMDV in specimens obtained during the acute stage of FMD and for identification of persistently infected cattle.

Animals↗