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Biomedical subjects

B Rossi

Publications and source records attributed to B Rossi.

At least 109 records · Page 6Linked to original sources

Different effects of levodopa and apomorphine on blink reflex recovery cycle in essential blepharospasm.

With the aim of assessing dopaminergic responsiveness in essential blepharospasm, we investigated the effects of oral levodopa and subcutaneous apomorphine on blink reflex recovery cycle in 7 blepharospasm patients. We found that in blepharospasm the excitability of the blink reflex recovery cycle was increased compared with control subjects. The oral administration of levodopa/carbidopa (500/50 mg) did not significantly modify the blink reflex recovery cycle. The 50 micrograms/kg dose of apomorphine decreased the amplitude of conditioned responses at 300 and 500 ms, whereas the 10 micrograms/kg dose was ineffective. We conclude that the excitability of the blink reflex recovery cycle in blepharospasm is partly under dopaminergic control. The partial normalization of the blink reflex recovery cycle excitability observed with 50 micrograms/kg apomorphine is consistent with the reported clinical efficacy of the drug in this condition.

Administration, Oral↗

Mild clinical expression of myasthenia gravis associated with autoimmune thyroid diseases.

Myasthenia gravis (MG) may occur in association with autoimmune thyroid diseases (AITD). The aim of this study was to evaluate the features of MG associated with AITD compared to those of MG without AITD. A total of 129 MG patients (34 men and 95 women; age range, 11-81 yr) were subdivided into: group A, 56 MG patients with AITD [25 with autoimmune thyroiditis and 31 with Graves' disease (GD)]; group B, 21 MG patients with nonautoimmune thyroid diseases; and group C, 52 MG patients without thyroid disease. The severity of MG was ranked according to the Osserman score. Laboratory evaluation included assays for antithyroid and antiacetylcholine receptor (AchRAb) antibodies. Ocular MG (Osserman's class 1) was more frequent in group A (41.0%) than in group B (14.2%; P < 0.03) or C (21.4%; P < 0.03). Severe generalized MG (classes > or = 2B) was more frequent in groups B (57.1%; P < 0.03) and C (51.9%; P < 0.02) than in group A (28.5%). GD patients with clinical evidence of ophthalmopathy had a higher frequency (P = 0.05) of ocular MG (57.8%) than GD patients without clinical ophthalmopathy (16.6%). Thymic disease was less frequent in group A (26.7%) than in group B (71.4%; P = 0.001) or C (59.7%; P = 0.001). The prevalence of thymic hyperplasia was 17.8%, 38.0%, and 40.3% in groups A, B, and C, respectively; the prevalence of thymoma was 8.9%, 33.4%, and 19.4%. When only patients with generalized MG were considered, thymic disease was less frequent (P < 0.02) in group A (40.6%) than in the remaining groups (69.4%). AchRAb was more frequent in groups B (57.1%) and C (57.6%; P < 0.03) than in group A (35.7%). In conclusion, MG associated with AITD has a mild clinical expression, with preferential ocular involvement and lower frequency of thymic disease and AchRAb. This supports the hypothesis that ocular and generalized MG are separate diseases with different spectra of associated diseases. Nonautoimmune thyroid diseases have no influence on the features of MG. The association of ocular MG and AITD might be due to a common autoimmune mechanism and/or a peculiar genetic background.

Adolescent↗

Human monocytes express amphiregulin and heregulin growth factors upon activation.

In the last few years, three new heparin binding growth factors that interact with the Epidermal Growth Factor receptor (EGFR) and/or the related p185erbB-2 tyrosine kinase have been identified. Amphiregulin (AR) and Heparin-Binding EGF-like growth factor (HB-EGF) bind and activate the EGFR while Heregulin (HRG) acts through the p185erbB-2 and p180erbB-4 tyrosine kinases. Recently, activated macrophages were reported to secrete a p185erbB-2- and a heparin binding EGFR-stimulatory activities. We show here that activated monocytes secrete AR, HRG and HB-EGF-like molecules. Indeed, upon activation with Phorbol12, 13-dibutyrate (PDBu), the human monocytic-like THP-1 cells expressed high levels of AR, HRG and HB-EGF transcripts and released heparin binding factors that induced tyrosine phosphorylation of the EGFR in A431 cells and a protein of 185 kDa in MDA MB 453 cells. Similarly, activation of peripheral blood monocytes induces a dramatic increase of these three genes. Since EGFR, cerbB-2, c-erbB-4 transcripts are not or hardly detected upon activation, the occurrence of autocrine loops in these cells is unlikely. Therefore, secretion of these factors by activated monocytes may be implicated in the paracrine activation of the erb receptors thereby contributing to the epithelial and connective tissue proliferation.

Amphiregulin↗

[Carcinoid of Vater's papilla. The authors' own experience].

Carcinoid tumours of the papilla of Vater, like all those of the gastroenteric tract, belong to the PUD system: in fact they excrete different amines and polypeptidic hormones that cause articulated and complex clinical features. We describe the clinical picture of a non secreting carcinoid tumour in a patient suffering from cholelithiasis in who jaundice has appeared after video-laparocholecystectomy; ERCP detected a papillary neoplasia which proved to be a carcinoid tumour at immunohistochemical investigation. The patient was submitted to surgical removal of the neoplasia by the trans-duodenal way. This kind of operation was chosen considering the small dimension of the tumour, the absence of lymph nodal and hepatic involvement and the elevated risk of pancreaticoduodenectomy. Eight months later hematic gastrine, NSE and total body scintigraphy with octreotide have shown normal values and the patients is in good clinical condition. The diagnosis of these tumours is always difficult when the typical hormonal syndrome is not present. The prognosis of this kind of tumours is better than others of the gastrointestinal tract due to the early symptoms (jaundice), and, consequently, of the treatment. A strict follow-up is recommended in these patients because a resumption of the tumour could also appear many years after the surgical intervention.

Aged↗

Tyrosine phosphorylation of I kappa B-alpha activates NF-kappa B without proteolytic degradation of I kappa B-alpha.

The transcription factor NF-kappa B regulates genes participating in immune and inflammatory responses. In T lymphocytes, NF-kappa B is sequestered in the cytosol by the inhibitor I kappa B-alpha and released after serine phosphorylation of I kappa B-alpha that regulates its ubiquitin-dependent degradation. We report an alternative mechanism of NF-kappa B activation. Stimulation of Jurkat T cells with the protein tyrosine phosphatase inhibitor and T cell activator pervanadate led to NF-kappa B activation through tyrosine phosphorylation but not degradation of I kappa B-alpha. Pervanadate-induced I kappa B-alpha phosphorylation and NF-kappa B activation required expression of the T cell tyrosine kinase p56ick. Reoxygenation of hypoxic cells appeared as a physiological effector of I kappa B-alpha tyrosine phosphorylation. Tyrosine phosphorylation of I kappa B-alpha represents a proteolysis-independent mechanism of NF-kappa B activation that directly couples NF-kappa B to cellular tyrosine kinase.

Alkaloids↗

Residual muscle cytochrome c oxidase activity accounts for submaximal exercise lactate threshold in chronic progressive external ophthalmoplegia.

The data from histological, biochemical, and mitochondrial DNA (mtDNA ) studies of muscle biopsies from 10 patients affected with chronic progressive external ophthalmoplegia (CPEO) were related to dynamic and metabolic parameters of incremental submaximal exercise. Maximum power output was reduced in all patients as compared to controls. Analysis of the venous lactate curve during exercise revealed a lactate threshold at exercise levels ranging from 40 to 50% of the predicted maximal power output. An earlier significant increase in lactate could be detected by calculating the mean delta lactate. Lactate values were inversely correlated with the cytochrome c oxidase (COX) activity of isolated muscle mitochondria. No relationship was found between lactate values and the number of ragged red fibers, or cytochrome c oxidase-negative fibers of the proportion of deleted mtDNA measured in muscle biopsy specimens. The discussion underscores the value of lactate kinetics in assessing skeletal muscle function, as well as the use of muscle COX levels to predict the effectiveness of wild-type complementation of deleted skeletal muscle mtDNA in in vivo contractile performance of CPEO subjects.

Adult↗

HIV induces activation of phosphatidylinositol 4-kinase and mitogen-activated protein kinase by interacting with T cell CD4 surface molecules.

T cell surface CD4 molecules act as co-receptors that amplify the T cell receptor (TcR)/CD3-induced signal transduction by a mechanism that requires the interaction of CD4 with p56lck tyrosine kinase (Veillette et al.; Nature 1989 338:257). Here, we demonstrate that in the absence of TcR signaling, heat-inactivated HIV-1 (HIV-HI) also elicits a cascade of events generally considered to convey a positive signal, such as protein tyrosine phosphorylation, phosphatidylinositol 4-kinase and mitogen-activated protein kinase activation. These results contribute to understand better the control that HIV may exert on its own replication or on T cell apoptosis by modulating the activation status of its target cells through its interaction with T cell surface CD4 molecules.

1-Phosphatidylinositol 4-Kinase↗

Muscle modifications in Parkinson's disease: myoelectric manifestations.

The muscle changes occurring in Parkinson's disease (PD) may come about as a consequence of the modified pattern of motor unit activation and rigidity, which are characteristic of the disease. A tendency towards hypertrophy of type I fibers and, in some instances, atrophy of type II fibers has been observed. Fourteen patients affected by PD and 10 age-matched controls were studied in order to investigate these muscle changes. We indirectly evaluated muscle modifications by measuring muscle fiber conduction velocity (CV) and median frequency (MDF) of the power spectrum using automatic analysis of surface EMG. The tibialis anterior muscle was selected for the study of contractions electrically induced by 35 Hz pulse trains lasting 30 s; the myoelectric signal was detected using the 4-bar electrode technique described by Broman et al. (Broman, H., Bilotto, G. and De Luca, C.J. Myoelectric signal conduction velocity and spectral parameters: influence of force and time. J. Appl. Physiol., 1985, 58: 1428-1437). Muscle biopsy specimens were obtained in 4 PD patients by surgical excision at the site where the EMG recording electrode had been placed. The main difference observed between PD subjects and controls was the rate of change of MDF and CV during the course of stimulated contraction; patients with PD sustained a smaller fatigue related decrease in both parameters compared to controls. According to our histological data, this result can be explained by a type I fiber percentage which accounts for 79% of the myofiber population on average. As expected, the CV basal values correlated directly with type I fiber diameter. These data suggest that non-invasive surface EMG techniques are useful in assessing the modifications of muscle characteristics that are observed in PD patients and for analyzing some aspects of the peripheral fatigue in this disease.

Aged↗

Evidence of strategic effects in the modulation of orienting of attention.

Two models of visual orienting of attention are frequently described. Voluntary orienting is usually induced by central cues that direct subjects' attention to a given location in the visual space. Automatic orienting is provoked by presentation of peripheral cues. It is shown that automatic orienting induces greater attentional costs and benefits, and is less under a subject's control (Jonides 1981). Furthermore, it is not similarly affected by factors such as signal eccentricity (Umiltà et al. 1991). The present experiment was undertaken to investigate how sensitive automatic orienting produced by peripheral cues is to voluntary modulations of attention. In experiment 1, subjects facing situations daily in which attentional requirements are high, were compared to non-practiced ones. In experiment 2, other groups of practiced subjects facing high or low attentional-demanding situations were tested. In both experiments, subjects were asked to respond to signals, presented in rapid succession, in one of two possible locations in space, on each side of central fixation point. The cue signal automatically oriented attention to one of the two locations in which a first stimulus was presented with 100% probability; 100 ms after the first response (RT1), a second response signal (RT2) was delivered either in the same location (valid condition) or in the opposite location (invalid condition). Four cue probabilities were manipulated for this second stimulus: 100%/0%, 80%/20%, 50%/50%, and 20%/80%. Two eccentricities of 3 degrees and 6 degrees were tested. RT2 data demonstrated that (1) there was no eccentricity effect; (2) the higher the cue probability, the greater were the attentional costs; (3) the attentional effects were smaller in the practiced subjects who faced attention-demanding situations daily, than in the other groups. Put together, these data suggest that automatic orienting of attention can be modulated by voluntary attentional processes, according to cue probability. Furthermore, experienced subjects seem to be able to better distribute their attentional resources in space, with increased task requirements. The adoption of an optimal criterion might lead to the use of a cost minimizing strategy.

Adult↗

Thrombin and trypsin-induced Ca(2+) mobilization in human T cell lines through interaction with different protease-activated receptors.

This study was conducted to determine whether serine proteinases may induce [Ca(2+)]i mobilization in different hematopoietic cell lines and to analyze their mechanisms of action. We show that in addition to thrombin and thrombin receptor agonist peptide (TRP, SFLLRN), trypsin induced [Ca(2+)]i mobilization in a highly thrombin-sensitive Jurkat T cell clone. Thrombin, TRP, and trypsin were found to induce [Ca(2+)]i release in three different Jurkat T cell clones differing in the level of T cell receptor expression. Similar results were obtained with a prothymocytic leukemic cell line, HPB.ALL, although these cells were much more responsive to trypsin than to thrombin and TRP. Other cell types such as THP1, a myelomonocytic cell line, or CEM, a CD4(+) positive leukemic cell line, were unresponsive to thrombin, TRP, and trypsin. The effect of trypsin was mimicked by SLIGRL, a peptide corresponding to the cleaved amino-terminal sequence of the recently characterized murine trypsin-activated receptor (PAR2). At suboptimal concentrations, the effects of SFLLRN and SLIGRL were additive, whereas saturating doses of peptides did not further increase [Ca(2+)]i mobilization in Jurkat T cells, indicating that both peptides were able to mobilize the same pool of calcium. Northern blot analysis of mRNAs from different leukemic cell lines indicated a remarkable correlation between PAR2 expression in different cell lines and SLIGRL or trypsin responses in the same cells. The expression of the "trypsin receptor" was also confirmed by polymerase chain reaction analysis. Moreover, a 24 h treatment of Jurkat cells by an anti-CD3 monoclonal antibody, a condition known to down-regulate thrombin receptor expression, induced loss of thrombin and TRP responses but only partially affected trypsin stimulation of [Ca(2+)]i release. Finally, after a first stimulation with either thrombin or trypsin, Jurkat cells were still able to respond to trypsin or thrombin, respectively, demonstrating that thrombin and trypsin essentially activated their own receptors. Our data provided evidence that 1) the human T leukemic cell line Jurkat and other T cell lines express at least two different functional protease-activated receptors, the thrombin receptor and a highly sensitive trypsin receptor, likely the human counterpart of the murine PAR2, and 2) at variance with the commonly accepted model, trypsin exerts most of its effect in T leukemic cell lines by thrombin receptor-independent mechanisms.

Animals↗

Body fluid overload and bioelectrical impedance analysis in renal patients.

Using a new bivariate vectorial approach to the standard bioimpedance analysis (tetrapolar, 50-kHz frequency), we evaluated the performance of a graphical method for the identification of patients with fluid overload. Two hundred and seventeen adult Caucasian subjects were divided into four classification groups: 86 healthy control subjects, 55 patients with mild-to-terminal chronic renal failure in conservative treatment (15% with apparent edema), 36 patients with idiopathic nephrotic proteinuria (58% with apparent edema), and 40 obese subjects. We found a bioimpedance threshold for apparent edema on the lower pole of the sex-specific 75% tolerance ellipse (bivariate tolerance interval) of the healthy population. This innovative graphical method allows identification, monitoring and therapy planning of patients with fluid overload using direct bioimpedance measurements without any assumption on body composition.

Adolescent↗

Stimulation of the T-cell antigen receptor-CD3 complex signaling pathway by the tyrosine phosphatase inhibitor pervanadate is mediated by inhibition of CD45: evidence for two interconnected Lck/Fyn- or zap-70-dependent signaling pathways.

The tyrosine phosphatase specific inhibitor pervanadate is a potent activator of T lymphocytes through induction of tyrosine phosphorylation and downstream events of the activation cascade. Using CD45- or CD3-negative variants of the Jurkat leukemic T-cell line we show that the different biochemical events induced by pervanadate appeared to be dependent on the presence at the cell surface of either CD45 or CD3. CD45-dependent events such as tyrosine phosphorylation of Shc, activation of nuclear factor-kappa B (NF-kappa B), activator protein-1 (AP-1), transcription factors, and stimulation of interleukin-2 (IL-2) promoter and of CD69 and CD25 surface expression paralleled activation of the tyrosine kinases lck and fyn. By contrast, stimulation of calcium influx, a CD3-dependent event, paralleled zap-70 activation. The data demonstrate that the T-cell antigen receptor-CD3 (TcR-CD3) complex is functionally linked to two different protein tyrosine kinase (PTK) modules with separate specific functions and that CD45 may be an important regulator of this coupling.

Base Sequence↗

Cyclic AMP stimulates a JunD/Fra-2 AP-1 complex and inhibits the proliferation of interleukin-6-dependent cell lines.

Interleukin-6 (IL-6) is a proinflammatory cytokine which also acts as a growth factor for some murine hybridomas (7TD1) or human myelomas (U266). We demonstrate that elevation of cAMP cellular content inhibits IL-6-stimulated cell growth, by blocking cells mainly in G1 phase. This inhibition is associated with increased expression of the Fos family protein Fra-2. Treatment of cells with 8Br-cAMP results in increased DNA-binding activity of two distinct AP-1 complexes; JunD/Fra-2 and JunB/Fra-2, and also in elevated AP-1 transactivation. When 8Br-cAMP is withdrawn from the medium, cells enter S phase and Fra-2 protein levels and AP-1 DNA-binding activity decrease to their basal value indicating that a temporally correlation exists between the 8Br-cAMP-mediated induction of JunD/Fra-2 AP-1 complex and the 7TD1 and U266 cell growth inhibition.

1-Methyl-3-isobutylxanthine↗

Two distinct signalling pathways are involved in the control of the biphasic junB transcription induced by interleukin-6 in the B cell hybridoma 7TD1.

We have measured the level of junB mRNA in the B hybridoma cell line 7TD1, under interleukin-6 (IL-6) stimulation. IL-6 increases junB mRNA in a biphasic fashion. The first early-induced peak was transient and likely corresponds to the well documented typical junB mRNA, stimulated in response to numerous growth factors, including IL-6. At variance, the second peak which has never been reported previously, lasted several hours. As a consequence of its effect on junB mRNA, IL-6 stimulated, in a biphasic fashion, the nuclear accumulation of the JunB protein. In this study, we demonstrated that IL-6 regulation occurred exclusively at the transcriptional level and that the bimodal increase of junB mRNA and JunB protein can be accounted for by a biphasic stimulation of junB transcription. Furthermore, our data point to two major differences between the mechanism of control of the early and the late IL-6-induced junB transcription waves. First, cycloheximide strongly potentiated the transcription of the second wave, whereas it failed to affect the early-induced burst. Second, tyrphostin, a tyrosine kinase inhibitor, impaired the expression of the first but not the second junB mRNA peak. Conversely, genistein, another tyrosine kinase inhibitor, totally abolished the expression of the second peak of junB mRNA whereas it did not affect the expression of the first peak. Altogether these data indicate that, in 7TD1 cells, IL-6 controls junB transcription in a biphasic fashion by means of two separate transduction pathways.

B-Lymphocytes↗