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Biomedical subjects

G Rubio

Publications and source records attributed to G Rubio.

At least 55 records · Page 3Linked to original sources

Interleukin-7 rescues human activated T lymphocytes from apoptosis induced by glucocorticoesteroids and regulates bcl-2 and CD25 expression.

We studied the ability of several interleukins to inhibit the cellular death of IL-2-dependent human T cells deprived of IL-2 testing viability, DNA integrity, and expression of bcl-2 gene product. Our in vitro results showed that the addition of IL-7, and in a far less efficient manner IL-4, augmented the viability of IL-2-dependent T-cell clones of different origin, specificity, and phenotype. Furthermore, IL-7 reduced the percentage of apoptotic T cells inhibiting DNA fragmentation. In addition, IL-7 but not IL-4 was consistently able to suppress the cell death of IL-2-dependent T cells triggered by DEX, a synthetic GC. The suppression of T-cell death triggered by IL-7 was not affected by the addition of anti-IL-2 antibody. Interestingly, IL-7 inhibited the downregulation of bcl-2 gene product expression that appeared on TCCs after IL-2 withdrawal and also shared with IL-2 the ability to induce the upregulation of CD25 antigen on activated T lymphocytes in the presence of DEX. These experiments establish a novel role for IL-7 in regulating viability and GC-induced apoptosis on activated human T cells and suggest that the maintenance of bcl-2 levels is a general mechanism by which interleukins preserve activated T cells from undergoing apoptosis.

Apoptosis↗

Reversed metal replicas of freeze-dried proteins to be visualized with the scanning tunneling microscope.

Scanning tunneling microscopy of metal-coated specimens has become a reliable technique that permits direct three-dimensional visualization of structural details at a level at which individual subunits in protein complexes or even single domains of proteins can be resolved. We describe in this paper a variation of the freeze-drying metal coating procedure that allows us to image with the STM the inner side of the metal replica, previously in contact with the protein molecules. We have tested this new approach with two different well characterized protein systems: freeze-dried two-dimensional crystals of bacteriophage phi 29 connector and the vesicle form of two-dimensional crystals of cytochrome oxidase from beef heart mitochondria. The images obtained have very good contrast and provide direct topographic information of the crystal surface, complementing structural information obtained previously with transmission electron microscopy. The resolution limit is imposed by the size (2-3 nm diameter) and corrugation of the metal grains used to prepare the replica and by the randomness of the metal shadowing.

Aluminum Silicates↗

Ethanol intake, plasma catecholamine levels, and ST-segment changes without myocardial injury in rats with short-term ethanol consumption.

The authors studied the effect of short-term ethanol consumption on the ST-segment and the association between ST-segment changes and the amount of daily ethanol intake and levels of plasma catecholamines. The study used 63 rats (control group n = 20, study group n = 43). The rats in the study group were exposed for 6 days to progressively larger doses of ethanol followed by 15 days of continuous exposure to ethanol. At baseline an electrocardiogram (ECG) was recorded, and on day 25 the ECG was repeated and plasma catecholamine levels were measured. The animals' hearts were removed and processed for histologic study. Repolarization abnormalities were observed in 68% of the ethanol-consuming rats. Two factors differentiated the subgroup of ethanol-consuming rats with ST-segment changes from the subgroup without ST-segment changes: amount of daily ethanol intake (0.0077 +/- 0.02 mL/g/d vs 0.0058 +/- 0.019 mL/g/d) and plasma epinephrine levels (3,881 +/- 733 pg/mL vs 1,478 +/- 406 pg/mL). No myocardial damage was detected. Our results suggest that in ethanol-consuming rats, high-volume daily ethanol intake and increased plasma catecholamines may mediate changes in the ST-segment.

Animals↗

[Current use of penicillin in community-acquired pneumococcal pneumonias].

BACKGROUND: A retrospective study was performed to know the clinical and microbiologic aspects of community-acquired pneumococcal pneumonia in adult patients admitted to a general hospital from 1990-1992. METHODS AND RESULTS: The medical records of 55 patients, aged 20-86 years (man age: 58 year) were reviewed. Streptococcus pneumoniae was isolated from blood in 45 cases (81.8%), transparietal lung puncture in 5 (9.1%), pleural fluid 3 (5.5%) and protected specimen brushing (> 1,000 UFC/ml) in 2 (3.6%) Most isolated (80%) were sensitive to penicillin (CIM < 0.1 microgram/ml); intermediate (CIM > or = 0.1 microgram/ml) 9 (16.4%) and resistant (> 1 microgram/ml) 2 (3.6%). Underlying diseases were present in 39 (70.9%) cases. All patients received empiric treatment with one or more antibiotics effective against Streptococcus pneumoniae. Only in 2 of the 9 cases treated with erythromycin the microorganism was resistant to this drug. Eleven patients died (20%), 5 died before to the fifth day of admission. Mortality was influenced by involvement of 2 or more lobes and immunosuppression (p < 0.05). CONCLUSIONS: This study suggests that 80% of the community-acquired pneumococcal pneumonia in a population with a high prevalence rate of disease requiring hospital admission are very sensitive in vitro to penicillin in contrast with its seldom clinical use in the authors environment. No microorganism presented with CIM above 2 micrograms/ml. Mortality was not due to inadequate therapy but rather to the severity of the underlying disease.

Adult↗

A novel functional cell surface dimer (kp43) serves as accessory molecule for the activation of a subset of human gamma delta T cells.

Kp43 is a cell surface molecule expressed by NK cells, gamma delta T lymphocytes, and a small subset of CD56+ alpha beta T cells. In the present study the distribution and function of Kp43 on gamma delta T cells is described. The expression of Kp43 on freshly isolated gamma delta T-cell populations derived from fetal and adult tissues was biased toward memory V gamma 2+/V delta 2+ T lymphocytes and appeared to be up-regulated after activation. Several gamma delta T-cell clones were derived from different sources. Adult V gamma 2+/V delta 2+ T-cell clones expressed the highest levels of Kp43, V delta 1 T-cell clones derived from periphery expressed moderate levels, whereas some thymus V delta 1 T cells and fetal gamma delta T-cell clones displayed low or undetectable levels of Kp43 molecule. Based on the effect of a specific mAb, this dimer appears to be fully functional as previously shown for NK cells. The stimulation of Kp43+ gamma delta T-cell clones with a combination of anti-CD3 and anti-Kp43 co-immobilized on a solid substratum enhanced both the expression of cell surface CD25 and the secretion of TNF-alpha. The restricted expression and functional activity of the Kp43 dimer suggests that it may play an important regulatory role in activation, selection, Ag recognition, and responsiveness of a subset of gamma delta T cells.

Antigen-Presenting Cells↗

ICAM-3, the third LFA-1 counterreceptor, is a co-stimulatory molecule for both resting and activated T lymphocytes.

Optimal activation of human T cells mediated by ligation of CD3/T cell receptor (TcR) complex requires co-stimulatory signals. These can be provided by the adhesive interaction between receptor molecules on T cells and their counter-receptors on antigen-presenting cells. Soluble ICAM-3, anti-ICAM-3 and anti-CD3 mAb were utilized to address the role of the ICAM-3/LFA-1 pathway in TcR/CD3-dependent or -independent T cell activation. Immunoaffinity-purified ICAM-3 co-immobilized with suboptimal concentrations of anti-CD3 monoclonal antibody (mAb) stimulated T lymphocytes as monitored by the expression of the lymphocyte activation antigens CD25 and CD69. The mechanism underlaying this activation appear to involve the interaction of ICAM-3 with a beta 2 integrin, likely to be LFA-1, since mAb to the CD18 chain completely inhibited T cell activation. Similar experiments demonstrated that anti-ICAM-3 mAb were able to co-stimulate both resting (cord blood) and activated (T cell clones) T lymphocytes. On the contrary, anti-ICAM-1 mAb were only co-stimulatory for CD25 expression on activated but not on resting T cells. In addition, we have found that some gamma delta T cell clones bearing the V delta 1 segment were activated by direct mAb engagement of ICAM-3 in the absence of TcR/CD3 occupancy. Furthermore, immobilized anti-ICAM-3 mAb also induced development of dendritic processes. In conclusion, our data suggest that ICAM-3 on the surface of both T cells and antigen-presenting cells plays an essential role in the initiation of the immune response.

Adult↗

Factitious systemic lupus erythematosus.

We report the case of a 15-year-old girl who simulated a complex clinical picture including cutaneous lesions, fever, arthralgia, asthenia and oliguria. A diagnosis of probable systemic lupus erythematosus (SLE) was assumed by numerous specialists and steroid therapy instituted. Factitious SLE should be considered for differential diagnosis of SLE, especially when laboratory evidence for autoimmunity is not demonstrated.

Adolescent↗

IgG anti-ganglioside antibodies and their subclass distribution in two patients with acute and chronic motor neuropathy.

IgG anti-ganglioside antibodies were found in two patients with motor neuropathy. The first patient had a chronic axonal neuropathy with persistently elevated anti-GM1 antibodies. The second patient had an acute axonal neuropathy with anti-GM1, GD1b and asialoGM1 antibodies. In both, the IgG subclass study showed that the antibodies belonged to the IgG1 subclass. An enzyme-linked immunosorbent assay (ELISA) for light chains revealed anti-ganglioside antibodies of the lambda type.

Acute Disease↗

Relapse to opiate use provokes biphasic changes of blood pressure in heroin-withdrawn addicts treated with clonidine.

The effect of relapse to opiate use on blood pressure and heart rate has been studied in heroin-withdrawn addicts treated with clonidine in an outpatient detoxification procedure. The daily dose of clonidine was established according to body weight and amount of heroin usually consumed at the onset of treatment. Patients who returned to heroin use were detected by increased urinary levels of opiates. Clonidine elicited significant reductions of blood pressure and heart rate reaching a plateau in the second day of treatment. Heroin consumption was found to provoke a further decrease of both systolic and diastolic pressure when the time interval between the relapse and the cardiovascular determinations was about 3 h as estimated by the patients. At longer intervals (16 h) this effect was reversed and both the hypotensive and the bradycardiac actions of clonidine seemed to be impaired. The possible impact of endogenous opioids and alpha-2 receptor sensitivity on these biphasic alterations is discussed.

Adult↗

CD26 induces T-cell proliferation by tyrosine protein phosphorylation.

CD26 antigen distribution among lymphoid cells and its participation in the process of lymphocyte activation and proliferation has been widely documented. However, the molecular and biochemical mechanisms coupled to the CD26 molecule are not yet known. With different monoclonal antibodies (mAb) we have detected that approximately 56% of CD4+ and 35% of CD8+ cells from peripheral blood lymphocytes express CD26 and the expression of this antigen is required for antigen- but not for mitogen-induced proliferation unless exogenous interleukin-2 (IL-2) is added to the culture. The stimulation of nylon wool-separated T cells and T-cell clones by the anti-CD26 mAb, 134-2C2, induced tyrosine phosphorylation on a subset of proteins of 50,000, 46,000, 26,000, 24,000 and 21,000 MW. This pattern of phosphorylation was not affected by the presence of 12-myristate 13-acetate (PMA), although this cofactor is required for CD26-mediated IL-2 mRNA expression and T-cell proliferation. When a specific tyrosine kinase inhibitor, Tyrphostin, was used in CD4+ cells cultures stimulated with 134-2C2 and PMA, the proliferation and the expression of IL-2 mRNA were inhibited. Thus, protein tyrosine phosphorylation seems to play a major role in CD26-mediated T-cell proliferation.

Adult↗

Gadolinium-DTPA MRI in the diagnosis of a patient with leptomeningeal metastasis produced by uvular carcinoma.

A patient with uvular cancer presented with lower limb weakness and paresthesiae, headache, neck stiffness and multiple cranial palsies. No malignant cells were found on lumbar puncture. CT, and MRI were normal. Gadolinium-DTPA MRI disclosed multiple enhancing lesions consistent with leptomeningeal metastases. Gd-DTPA MRI is the best technique to demonstrate tumoral meningeal infiltration in cytology-negative patients suspected of having leptomeningeal metastases.

Carcinoma, Squamous Cell↗

[Evaluation of bronchoalveolar lavage in the microbiological diagnosis of pneumonia in patients at risk].

Bronchoalveolar washout was performed in 130 patients with pneumonia during a period of 28 months. Microbiological investigation involved common bacteria, Legionella, fungi, viruses (Cytomegalovirus, herpes, RSV), Mycobacterium, and Pneumocystis carinii. Infection HIV was present in 75% of patients. The remaining patients had malignant diseases or severe pneumonia. The overall sensitivity of the technique was 65.4% and the positive predictive value was 92%. The technique was less sensitive in cases of bacterial pneumonia (sensitivity = 34.4%). This was attributed to the fact that 82.8% of these cases received antibiotic therapy. Pneumocystis carinii and Mycobacterium tuberculosis were the most common agents (44.8% and 34.5%, respectively). In seven instances the clinical picture was related to cytomegalovirus, although this diagnosis can not be easily done.

Adolescent↗