Biomedical subjects

A Postigo

Publications and source records attributed to A Postigo.

7 recordsLinked to original sources

PubMed2001

A novel type of nucleophilic substitution reactions on nonactivated aromatic compounds and benzene itself with trimethylsiliconide anions.

[reaction: see text]. The reaction of fluorobenzene with Me3Si- anion (1) in HMPA at room temperature surprisingly affords o- and p-fluorotrimethylsilylbenzenes (substitution of aromatic H for TMS, 76% yield) 7a and 7b and also 14% of trimethylsilylbenzene (2). Benzene itself reacts at 50 degrees C to furnish 4 in 45% yield. Pyridine affords p-trimethylsilylpyridine quantitatively. Mechanistic studies are presented.

Anions↗

PubMed1998

Point mutation in trkB causes loss of NT4-dependent neurons without major effects on diverse BDNF responses.

Neurotrophins are a family of soluble ligands that promote the survival and differentiation of peripheral and central neurons and regulate synaptic function. The two neurotrophins, brain-derived neurotrophic factor (BDNF) and neurotrophin-4 (NT4), bind and activate a single high-affinity receptor, TrkB. Experiments in cell culture have revealed that an intact Shc adaptor binding site on TrkB and subsequent activation of the Ras/MAPK pathway are important for neuronal survival and neurite outgrowth. To elucidate the intracellular signaling pathways that mediate the diverse effects of BDNF and NT4 in vivo, we have mutated in the mouse germline the Shc binding site in the trkB gene. This trkB(shc) mutation revealed distinctive responses to BDNF and NT4. While nearly all NT4-dependent sensory neurons were lost in trkB(shc/shc) mutant mice, BDNF-dependent neurons were only modestly affected. Activation of MAP kinases and in vitro survival of cultured trkB(shc/shc) neurons were reduced in response to both neurotrophins, with NT4 being less potent than BDNF, suggesting differential activation of TrkB by the two ligands. Moreover, while the Ras/MAPK pathway is required for in vitro differentiation of neuronal cells, trkB(shc/shc) mutant mice do not show any defects in BDNF-dependent differentiation of CNS neurons or in the function of sensory neurons that mediate innocuous touch.

Animals↗

PubMed1996

Expression and function of alpha 4/beta 7 integrin on human natural killer cells.

In this report we have analysed the expression and function of the alpha 4/beta 7 heterodimer in human natural killer (NK) cells. The expression of alpha 4 beta 7 is induced in NK cells upon activation as the anti alpha 4 beta 2 ACT-1 monoclonal antibody (mAb) family stained a minority of peripheral blood NK cells, whereas it strongly reacted with in vitro long-term interleukin-2 (IL-2)-activated NK cells. Incubation with ACT-1 on its F(ab) fragments induced a strong homotypic adhesion of NK cells, comparable to than stimulated by the anti-alpha 4 HPI 7 mAb. Cell cell interaction induced by the ACT-1 mAb was only prevented by another anti-alpha 4 mAb (HP2.1) that recognizes a different epitope. In alpha 4 beta 7-mediated cell aggregation the alpha 4 beta 7 heterodimer was redistributed to intercellular contact sites thus, suggesting a direct involvement of this integrin in the formation of cell clusters. In NK cells attached to Fibronectin (FN38) or vascular cell adhesion molecule-1 (VCAM-1), both alpha 4 beta 7 and alpha 4 beta 7 integrins were redistributed at the ventral cellular membrane forming discrete contact sites. The ACT-1 mAb only partially blocked NK cell binding to FN38, but in combination with the anti-beta 7 mAb LIAI 2, NK cell binding to FN38 was completely inhibited. In contrast. ACT-1 did not modify NK cell adhesion to VCAM-1 thus supporting the theory that the alpha 4 beta 7 binding sites for both ligands appear to be different. Our results indicate that upon IL-2-activation, expression of functional alpha 4 beta-integrin is induced on NK cells potentially participating in their interaction with both extracellular matrix and endothelial cells.

Cell Adhesion↗

PubMed1995

Hematopoietic cell-type-dependent regulation of leukocyte integrin functional activity: CD11b and CD11c expression inhibits LFA-1-dependent aggregation of differentiated U937 cells.

To study the influence of the cellular environment on the functional activity of leukocyte integrins and to analyze their involvement in hematopoietic cell differentiation, we have developed stable transfectants of LFA-1, Mac-1, and p150,95 (CD11a-c/CD18) leukocyte integrins in cultured cell lines whose differentiation can be induced in vitro. As on circulating leukocytes, the integrins expressed on U937 or K562 cells were expressed in a constitutively inactive state, as demonstrated by the lack of adhesion to their cellular counterreceptors or soluble ligands, the absence of CD18-dependent intercellular aggregation, and their inability to mediate adhesion to protein-coated plates. However, while leukocyte integrin adhesive functions in U937 cells were induced upon treatment with cellular agonists (e.g., PMA), their function in K562 cells could be upregulated only with activating monoclonal antibodies, demonstrating the cell-type-specific regulation of the adhesive capabilities of the three leukocyte integrins in hematopoietic cellular environment. On the other hand, the expression of either CD11b/CD18 or CD11c/CD18 in U937 myeloid cells before induction of differentiation greatly affected the adhesive phenotype of differentiating cells by abrogating the CD11a/CD18-CD54-dependent homotypic aggregation. Unlike that of mock-transfected U937 cells, differentiation of CD11b/CD18- or CD11c/CD18-transfected U937 cells led to cell adhesion and spreading on the tissue culture plates, with an almost total absence of homotypic aggregates. These results confirm the role of CD11b/CD18 and CD11c/CD18 in myeloid cell adhesion and spreading and suggest that the CD11b/- and CD11c/CD18-mediated recognition of substrate-bound ligands competes or interferes with LFA-1-dependent intercellular adhesion.

Cell Adhesion↗

PubMed1995

Blood lactate and ammonia in short-term anaerobic work following induced alkalosis.

This study was designed to investigate the effect of an induced metabolic alkalosis on a 300 m sprinting time in six elite 400 m runners. The subjects competed as pairs, on two separate occasions, in a standard racing format, three hours after ingestion of either an alkaline (sodium citrate, 0.5 g.kg-1 body weight) or a placebo solution (calcium carbonate, 0.5 g.kg-1 body weight). The results showed that following alkaline ingestion mean sprinting time was not improved. Peak blood lactate during recovery was higher after sodium citrate administration than after placebo (19.88 +/- 2.09 vs 18.82 +/- 1.84 mmol.l-1, p < 0.01). No difference was observed in peak blood ammonia between the alkaline and placebo treatments (187.0 +/- 37.0 vs 188.8 +/- 49.0 mumol.l-1). The absence of effects on performance confirms that when exercise of short duration (30 to 40 s) is used, alkaline agents have minor or no effects on performance. The altered relationship observed between blood lactate and ammonia under placebo and buffering loading conditions suggests that the regulation of lactate and ammonia metabolism is unrelated.

Adult↗

PubMedDate not supplied

[Long-latency auditory evoked potentials in cochlear implants].

Cortical evoked potentials were evaluated in patients with cochlear implants. In a group of 8 adults of different ages, the lingual state before implantation and during rehabilitation were evaluated. Using cortical evoked potentials, the results of the P300 wave in response to two tones, one frequent (1,000 Hz) and the other infrequent (2,000 Hz), presented at 70 and 80 dB HL were studied. Results were analyzed and compared in relation to locutive state, rehabilitation stage, and intensity of stimulus. Absolute latencies did not differ significantly. However, latency values in relation to reaction time were significantly longer in prelingual than in postlingual patients (p < 0.05, Student < > test). The results confirmed the normality of central cognitive processes in patients with cochlear implants in objective assessment of P300 latency. The results suggest differences between prelingual and postlingual patients in relation to central signal processing.

Acoustic Stimulation↗

PubMedDate not supplied

[Olfactory cortical evoked potentials].

The objective evaluation of smell is the least used functional ear, nose and throat exploration. Evoked potentials can be recorded after chemical olfactory stimulation using a method similar to recording cortical auditory evoked potentials. Our results with this technique and peppermint oil as the stimulant were fully satisfactory. In 10 patients with normal smell, a characteristic wave with a long latency was recorded in the absence of auditory and visual stimuli. In contrast, in 10 anosmic patients this characteristic recording was absent. The easy recording technique proposed here can be useful for olfactory assessment of objective disorders, detection of malingers, and medical-legal reports.

Adult↗