Search PubMed⌕ Search

Biomedical subjects

M Lopez

Publications and source records attributed to M Lopez.

At least 523 records · Page 29Linked to original sources
PubMedDate not supplied

Transmembrane signaling via both CD3 and CD2 human T cell surface molecules involves protein kinase-C translocation.

The activation of T lymphocytes by appropriate pairs of anti-CD2 monoclonal antibodies has been shown to involve phospholipase-C and phosphoinositide hydrolysis. In this paper we show that the stimulation of the human cloned leukemic T cell line Jurkat by anti-CD2 as well as anti-CD3 monoclonal antibodies induces translocation from cytosol to cell membrane of protein kinase-C (PKC), which is dependent on the formation of 1,2-diacylglycerol from inositol 4,5-diphosphate. PKC translocation is rapid and transient: the kinetics of enzyme redistribution are similar for CD2 and CD3. These results further stress that CD2 and CD3 T cell activation pathways use similar signal transducing mechanisms.

Antibodies, Monoclonal↗
PubMedDate not supplied

Acute lymphocytic leukemia and complement receptors. (A study of 45 cases).

The expression of complement receptors (C3R) associated or not to sheep erythrocyte receptors (ER) and surface membrane immunoglobulins (SmIg) was determined on lymphoblasts of 45 patients with acute lymphocyte leukemia (ALL) at onset and/or in the first relapse. We found C3R simultaneously expressed with ER or SmIg on lymphoblasts of T cell ALL and B cell ALL. Lymphoblasts were positive for C3R in absence of ER and SmIg only in three patients in the hematological relapse. We stress the importance to find C3R as independent marker on ALL cells at onset and in subsequent relapses.

Adolescent↗
PubMedDate not supplied

Natural Leishmania infection of Lutzomyia spp. in Peru.

Natural infection of Lutzomyia spp. with Leishmania was studied with the aid of the polymerase chain reaction (PCR) in Chaute, Lima, Perú, a locality endemic for Andean cutaneous leishmaniasis (uta). The PCR, with primers specific for the L. braziliensis complex, was applied to sandfly pools. Sandflies were sampled from April 1990 to May 1991 with CDC light traps in homes, and from near homes with a Shannon trap using protected human bait. Lu. verrucarum (4 pools) and Lu. peruenis (2 pools) from the anthropophilic collections, and Lu. verrucarum (2 pools) from indoors were found to be infected with Leishmania. The majority of infected sandflies were recorded mainly in April 1991 (4 pools), coinciding with the highest sandfly densities and the maximum number of new cases of uta (7). Non-infected sandflies were found from May to October 1990 and January to March 1991. Thus, these 2 sandfly species play a role in the spread of leishmaniasis among humans and other animals in Chaute.

Animals↗
PubMedDate not supplied

Dissociation between early and late events in T cell activation mediated through CD28 surface molecule.

The regulation of early and late events of T cell activation via the CD28 molecule has been investigated, using as an indicator system the differentiated leukemic T cell line Jurkat. Both CD3 and CD28 mAbs induced an increase in (Ca2+)i in Jurkat cells, although with different kinetics, the latter being slower than the former. CD28-mediated (Ca2+)i mobilization was highly sensitive to cholera toxin (ID50 25 ng/ml, vs 300 ng/ml for CD3 stimulation). The inhibitory action of cholera toxin was neither merely due to the increase in intracellular cAMP concentrations, nor to decrease in cell surface expression of the CD28 molecule. To evaluate the effects of cholera toxin on late events of Jurkat cell activation induced by CD28 and CD3 mAbs, the action of cholera toxin and cAMP and CD3- and CD28-mediated IL-2 secretion was analyzed. CD3-induced IL-2 secretion was highly sensitive to cholera toxin (ID less than 5 ng/ml); on the other hand, CD28-induced IL-2 secretion was poorly sensitive to cholera toxin, in sharp contrast to (Ca2+)i mobilization. On the basis of these data, it is hypothesized that the CD28 pathway could be associated with at least two distinct transduction mechanisms, one responsible for the (Ca2+)i rise in Jurkat cells and highly sensitive to cholera toxin, and the other, whose second messenger is unknown, resistant to cholera toxin and responsible for IL-2 secretion.

Antibodies, Monoclonal↗
PubMedDate not supplied

Mild core hyperthermia does not alter electroencephalographic responses during epidural-enflurane anesthesia in humans.

STUDY OBJECTIVES: To determine the electroencephalographic (EEG) changes induced by mild hyperthermia during enflurane anesthesia and to test the reliability of two new infrared thermometers. DESIGN: Prospective laboratory evaluation. SETTING: The Thermoregulation Research Laboratory at the University of California, San Francisco. VOLUNTEERS: 6 healthy female volunteers aged 30 +/- 8 years. INTERVENTIONS: Epidural anesthesia (approximately T10 dermatome) was induced and maintained using 2-chloroprocaine anesthesia. General anesthesia was induced by inhalation of nitrous oxide and enflurane and maintained with enflurane at an end-tidal concentration of 1.7%. A minimum of 2 degrees C core hyperthermia was induced by active cutaneous warming, and the volunteers subsequently were passively cooled. MEASUREMENTS AND MAIN RESULTS: EEG data were recorded from gold cup electrodes positioned at FP1 and FP2, with the reference electrode at CZ and the ground lead on the mastoid. In addition to routine EEG parameters, we evaluated the bispectral index. Bispectral analysis quantifies the phase coupling between various frequencies in the power spectrum and may be a useful measure of anesthetic depth. Core temperature was measured at the left tympanic membrane and distal esophagus. Core temperature also was determined from the right ear using two new, infrared tympanic membrane thermometers. One of these directly measures tympanic temperature, and the other extrapolates core temperature from the external ear canal. Induction of 2 degrees C core hyperthermia did not produce statistically significant or clinically important changes in beta or delta power, the 95% spectral edge frequency, or the bispectral index. Temperatures recorded from the right ear by the direct thermometer were 0.27 degrees C +/- 0.33 degrees C less than those measured in the left ear, but the values correlated well (r2 = 0.95 +/- 0.04). Temperatures recorded from the right ear by the core temperature extrapolater were 0.42 degrees C +/- 0.33 degrees C lower than those measured in the left ear, and the correlation between values was slightly worse (r2 = 0.83 +/- 0.16). CONCLUSIONS: Since mild core hyperthermia does not alter routine EEG parameters or the bispectral index, typical perianesthetic thermal disturbances are unlikely to obscure EEG estimates of anesthetic depth. Both the direct thermometer and the core temperature extrapolater were found to be sufficiently accurate and precise for routine clinical use, but the direct thermometer would be preferable in the perioperative period.

Adult↗
PubMedDate not supplied

Lateral parabrachial lesions impair taste aversion learning induced by blood-borne visceral stimuli.

The lateral parabrachial area (LPB), main relay from the area postrema (AP), plays a role in processing visceral information and is thus of potential importance in taste aversion learning (TAL). This study used a lesion approach to address whether LPB functional relevance depends upon the features of toxins that serves as visceral stimuli in TAL. In addition, we explored whether LPB involvement in TAL is restricted to those toxic events detected by the AP or whether it has a more general role. Results showed that LPB-lesioned animals were disrupted in acquiring a TAL induced by blood-borne AP-dependent aversive stimuli (intraperitoneal methylscopolamine) and by AP-independent stimulus (intraperitoneal ethanol), but still, clearly developed strong aversions when intragastric hypertonic sodium chloride, a vagally processed aversive stimulus, served as the aversive stimulus. These findings suggest that the LPB plays a critical role in TAL induced by blood-borne toxins, such as methylscopolamine or ethanol, but is not necessary for vagally mediated stimulus, such as sodium chloride. The present results are discussed in the context of the hypothesis holding separable and independent neural systems underlying TAL.

Animals↗
PubMedDate not supplied

Clinical relevance of radionuclide angiography and antimyosin immunoscintigraphy for risk assessment in epirubicin cardiotoxicity.

BACKGROUND: Cardiotoxicity is the major limiting factor in anthracycline chemotherapy of advanced neoplastic disease. Epirubicin shows a more favorable therapeutic index than does doxorubicin, but it is still cardiotoxic. Limited data regarding epirubicin cardiotoxicity are available, and suggested guidelines for doxorubicin with left ventricular ejection fraction (LVEF) measurement may not be empirically useful for epirubicin therapy. This study evaluates the diagnostic role of antimyosin immunoscintigraphy for early identification of patients at risk for late pump dysfunction from cardiotoxicity induced by high-dose administration of epirubicin up to high cumulative dosages. METHODS AND RESULTS: Chemotherapy with epirubicin was administered to 36 patients with cancer at a dosing rate of 160 mg/m2 as a bolus injection every 21 days to a cumulative dosage of 960 mg/m2. Radionuclide angiography (LVEF) and antimyosin immunoscintigraphy with heart-lung ratio (HLR) measurements were performed before chemotherapy, at intermediate cumulative epirubicin dosages, at the end of treatment, and during the follow-up. LVEF decreased significantly at the end of the treatment and after therapy discontinuation. HLR values were significantly increased at intermediate epirubicin dosage levels and continued to increase to the end of the treatment but thereafter remained substantially unmodified for 3 to 6 months after therapy discontinuation. A value of HLR >1.85 at intermediate epirubicin dosage level showed a sensitivity of 95% and a specificity of 57% as a predictor of late LVEF impairment. CONCLUSIONS: LVEF appears more useful at high cumulative dosages and during follow-up to monitor late pump dysfunction, whereas HLR may be effective during the early phase of the therapy in determining which patients are at risk for development of late cardiac dysfunction.

Adolescent↗
PubMedDate not supplied

Quantitative and thermodynamic studies of erythrocytic ABO antigens.

This paper presents recent data from quantitative and thermodynamic investigations on A and B erythrocyte antigens. In regard to weak A phenotypes on the basis of quantitative data, practically no gap is observed from the weakest Aend to the strongest A3. Weak B phenotypes give a similar distribution. However, a more precise structural analysis including kinetics and thermodynamic measurements provides convincing evidence for the heterogeneity of each type of weak B reactive structures. Weak B antigens appear to be different from one to another, but similar inside one family. However, thermodynamics failed to demonstrate a qualitative difference between the weak B antigen in BX groups and the enhanced B antigen in ABX heterozygote, phenomenon that occurs in some very rare families. The same data were obtained from kinetic and thermodynamic analysis of B reactivity in cis AB samples; it can be assumed that such mutants are all different.

ABO Blood-Group System↗
PubMedDate not supplied

Positive selection of autologous peripheral blood stem cells.

The development of monoclonal antibodies against differentiation antigens on human haematopoietic cells has led to a new concept in stem cell purification: the positive selection. In terms of autologous PBSC transplantation, the immature stem cells are identified by their expression of a specific antigen, the CD34. The CD34 antigen is expressed on early lymphohaematopoietic stem cells and progenitor cells, but not on mature blood cells or on tumour cells of several diseases. CD34+ cells are found in low numbers in bone marrow (<2%) and in even lower numbers in steady state blood (<0.01%) but may increase from 1 to 5% after mobilization using chemotherapy and/or growth factors. Several techniques have been set up to enrich PBSC grafts in CD34+ stem cells. The quality of each system is here analysed in terms of CD34 purity of the selected cell fraction, the CD34 cell recovery, the tumour cell depletion efficiency and the functional capacity ex vivo and in vivo of the selected cells. The final CD34+ cell purity of the selected fractions is correlated to the concentration of CD34+ cells before selection. The optimal recoveries and the highest purities were generally obtained when the initial CD34 content was roughly over 1%. Below this figure, the final purity seems to be less predictable. Besides the better tolerance resulting from the reduction in the number of autologous cells, and consequently the total volume of DMSO reinfused to the patient, the selective enrichment of the CD34 cell population offers a new approach to tumour purging. The procedure by itself results in elimination of about 99% in the total number of initial cells, thus allowing reduction of the overall tumour cell number in the final autograft. However, its major interest is that, in diseases where tumour cells do not express the CD34 antigen, it is theoretically able to completely eliminate the tumour contamination of the graft. Based on previous data showing that lymphoma, myeloma, neuroblastoma and breast cancer cells are not CD34+, pilot clinical trials for the separation and transplantation of CD34+ cells selected from PBSC of patients with these diseases have recently been conducted. The efficacy of CD34 selection in reducing the tumour load of the PBSC of patients with these diseases has been reported. However, the efficacy of purging may greatly differ between individual patients, and complete eradication of contaminating cells from PBSC grafts was not always reached. There is now evidence that purified CD34+ cells are capable of supporting haematopoietic reconstitution in autologous transplantation. However, until now no study has demonstrated clear evidence that the reduction of tumour cells from PBSC of patients by CD34+ cell selection resulted in a lower relapse rate post-transplant, as compared to unselected PBSC infusion.

Antigens, CD34↗
PubMedDate not supplied

Effects of intravenous diltiazem on sinus node function and atrioventricular conduction in patients.

We studied the electrophysiologic effects of injectable diltiazem (dosage: bolus of 0.15 mg/kg, maintenance infusion of 0.3 mg/kg/h for 20 min) on sinus node function and atrioventricular function in 33 patients (22 men and 11 women, mean age 63.6 +/- 15.8 years). Seventeen patients had an electrophysiological exploration considered as normal, eight had sinus node dysfunction (corrected sinus recovery time greater than 525 ms), and eight had AV nodal block (PH greater than 160 ms and/or a Wenckebach point less than 125/min). Effects of the drug were assessed 20 min after the beginning of the infusion, which was continued until the end of examination. In normal subjects diltiazem lengthened corrected sinus node recovery time (305 +/- 115 ms leads to 451 +/- 283 ms) and slightly depressed AV nodal conduction (Wenckebach point: 163 +/- 23 leads to 147 +/- 25). In patients with sinus node dysfunction diltiazem provoked a bradycardia without significant changes in corrected sinus node recovery time or in estimated atrio-sino-atrial conduction time. In patients with AV nodal block diltiazem provoked a lowering of the Wenckebach point (137 +/- 47 leads to 122 +/- 38). There was no effect on hissian or infrahissian conduction, even when this was abnormal in the basal state. These data suggest that diltiazem must be utilized with caution in patients with sinus node dysfunction and AV nodal block.

Aged↗
PubMedDate not supplied

Vinorelbine and mitomycin C in anthracycline-pretreated patients with advanced breast cancer.

At present, there is no satisfactory treatment for advanced breast cancer patients who have become refractory to anthracyclines. Vinca alkaloids and mitomycin C (MMC) are among the drugs most frequently used in this setting. Recently, vinorelbine (VNR) has been reported to be highly active in advanced breast cancer. Sixty advanced breast cancer patients previously treated with anthracyclines have been exposed to VNR 25 mg/m2 i.v. on days 1 and 8, and MMC 10 mg/m2 i.v. on day 1, with cycles repeated every 4 weeks. There were 3 complete and 21 partial responses for an overall response rate of 40% (CI 95%: 28-52%). Median duration of response and median survival were 7 and 10 months, respectively. Myelosuppression was the dose-limiting toxicity, but it was generally mild to moderate. Although this combination appears to be effective and well tolerated, every effort should be made to further improve treatment results in anthracycline-pretreated advanced breast cancer.

Adult↗
PubMedDate not supplied

Sequential subcutaneous thymopentin, interferon alpha-2a and interleukin-2 in metastatic renal cell cancer.

To determine the activity of sequential administration of thymopentin (TP-5), interferon alpha-2a (IFN) and interleukin-2 (IL-2) in metastatic renal cell cancer (RCC), 17 patients with RCC were treated with TP-5 50 mg/d on days 1 to 14, IFN 3 MIU/d on days 14, 15, 21, 22 and IL-2 18 MIU/d on days 16 to 20, and 23 to 27. Treatment was given subcutaneously and cycles were repeated every 6 weeks. All patients were assessed for toxicity and response. No objective responses were observed. Two patients had a short-lived disease stabilization. Median survival was 9 months. Toxicity was generally moderate. The most important side-effects were related to IL-2 administration. In view of the lack of antitumor activity, the combination of TP-5 + IFN + IL-2 in the doses and schedule used in this trial cannot be recommended. The investigation of chemotherapeutic and immunological agents that can effectively synergize with IFN or IL-2 is essential.

Adult↗
PubMedDate not supplied

Paclitaxel activity in anthracycline refractory breast cancer patients.

AIMS AND BACKGROUND: We investigated the efficacy and tolerability of two doses of paclitaxel, 175 mg/m2 and 135 mg/m2, over a 3-hr infusion, without prophylactic G-CSF, in heavily pretreated patients with anthracycline-resistant breast cancer. Although paclitaxel may share with anthracyclines a common mechanism of drug resistance, there is evidence that the two drugs are not completely cross resistant. METHODS: From July 1994 to January 1996, 42 patients were treated every 3 weeks, for a maximum of 6 cycles; paclitaxel dose was established according to pretreatment extension. RESULTS: In 41 assessable patients we observed 9 partial responses, for an overall response rate of 22% (95% CI, 10-34%). There was no difference in response rate between the two dose levels. Median duration of response was 9 months, median time to progression 5 months, and median survival 9 months. The dose-limiting toxicity was neutropenia, which was grade 3-4 in 40% (135 mg/m2) and 62% (175 mg/m2) of the patients (P = 0.28); neutropenic fever occurred in 24% of the patients, without significant differences between the two dose levels. Other toxicity was mild to moderate. CONCLUSIONS: Paclitaxel at doses of 175 mg/m2 or 135 mg/m2 is active and well tolerated in advanced breast cancer patients resistant to anthracyclines. The prophylactic use of colony-stimulating factors seems appropriate in heavily pretreated patients given the higher dose level.

Adult↗
PubMedDate not supplied

Neuroimmunological effects of exposure to methylmercury forms in the Sprague-Dawley rats. Activation of the hypothalamic-pituitary-adrenal axis and lymphocyte responsiveness.

The effects of different methylmercury (MeHg) forms on the immune system and the hypothalamic pituitary adrenal (HPA) axis were assessed. The lymphocyte response to Concanavalin A (Con A) stimulation, blood levels of interleukin-6 (IL-6), adrenocorticotrophin hormone (ACTH), and corticosterone in the presence of different MeHg compounds was measured. Rats were exposed to methylmercury sulfide [(MeHg)2S] and methylmercury chloride (MeHgCl) at concentrations of 5 and 500 micrograms per liter in the drinking water for 8 or 16 weeks. Short-term exposure (8 weeks) at both, low- and high-doses of (MeHg)2S significantly enhanced lymphocyte responsiveness. MeHgCl only induced increased lymphocyte responsiveness at the low-dose exposure. Circulating levels of IL-6 after short-term exposure were increased in the MeHgCl-exposed group. The HPA axis activation was demonstrated by increased levels of ACTH and corticosterone levels. This response was predominant in low-dose exposed animals. Long-term (16 weeks) exposure resulted in a reduction in lymphocyte prolife ration after both low- and high-dose MeHgCl exposures. The (MeHg)2S exposure resulted in a 3-fold increase in the proliferative response. Levels of ACTH were elevated 3-fold in the (MeHg)2S-exposed group and no increase of corticosterone was observed in the high-dose exposed group at 8 weeks, no effect of (MeHg)2S was observed at 16 weeks. The MeHgCl exposed group showed an increase in ACTH and corticosterone levels at 8 weeks; this response was not observed at 16 weeks. These data indicate that exposure to MeHg compounds enhances T-cell proliferation in most of the cases, in a dose- and time-dependent fashion. Release of IL-6 also depends on the length of exposure. Early increases in circulating ACTH at 8 weeks also suggest activation of the HPA axis. This may contribute to the production of IL-6 and surveillance of regulatory homeostatic responses against environmental agents that mimic stress-like responses.

Administration, Oral↗