Bidirectional regulation of neurite elaboration by alternatively spliced metabotropic glutamate receptor 5 (mGluR5) isoforms.

Alternative splicing in the mGluR5 gene generates two different receptor isoforms, of which expression is developmentally regulated. However, little is known about the functional significance of mGluR5 splice variants. We have examined the functional coupling, subcellular targeting, and effect on neuronal differentiation of epitope-tagged mGluR5 isoforms by expression in neuroblastoma NG108-15 cells.

The use of in vivo direct drug application to assess neural regulation of muscle properties.

Skeletal muscle is a convenient model system for studying basic questions on the neural regulation of synaptogenesis and of many properties of sarcolemma and contractile apparatus. The study of the neural signals involved in a particular regulation and of the mediating intracellular pathways, requires the chronic application of drugs, second messengers, antibodies, trophic factors and the like. The most common way of application is in vitro treatment of muscle cell lines or primary myotube cultures.

Intravenous clomipramine decreases excitability of human motor cortex. A study with paired magnetic stimulation.

Several recent reports suggest the possibility of monitoring pharmacological effects on brain excitability through transcranial magnetic stimulation (TMS). In these studies, paired magnetic stimulation has been used in normal subjects and on patients who were taking different antiepileptic drugs. The aim of our study was to investigate motor area excitability on depressed patients after intravenous administration of a single dose of clomipramine, a tricyclic antidepressant.

Transforming growth factor-beta1 gene polymorphism, bone turnover, and bone mass in Italian postmenopausal women.

Transforming growth factor beta1 (TGF-beta1) is abundant in bone and is an important regulator of the osteoclastic-osteoblastic interaction (coupling). The sequence variation, 713-8delC in the TGF-beta1 gene has previously been found to be associated with very low bone mass in osteoporotic women and with increased bone turnover in both osteoporotic and normal women. The possible association of this polymorphism with bone mass and bone turnover has now been investigated in 256 postmenopausal Italian women.

Hebbian mechanisms revealed by electrical stimulation at developing rat neuromuscular junctions.

Synapse competition and elimination are widespread developmental processes, first demonstrated at neonatal neuromuscular junctions. Action potential activity was long shown to exert a powerful influence, but mechanisms and contribution relative to other factors are still not well understood. Here we show that replacement of natural motoneuronal discharge with synchronous activity suppresses elimination of polyneuronal innervation of myofibers.

Interleukin-6 repression is associated with a distinctive chromatin structure of the gene.

Expression of the interleukin-6 (IL-6) gene is usually tightly controlled and may be induced in specific tissues only after treatment with appropriate stimuli. The molecular mechanisms responsible for IL-6 gene repression in specific tissues or cell lines remain poorly defined. In order to address this question we have studied two human breast carcinoma cell lines, MDA-MB-231, in which the IL-6 gene is expressed, and MCF-7, in which it is not.

Effects of sodium selenite on in vitro interactions between platelets and endothelial cells.

Selenium is an essential component of glutathione peroxidase enzymes, which protect cells against peroxidation and control concentrations of intracellular proxides. Since selenium deficiency is associated with an increased incidence of arterial thrombosis, we studied the effect of selenium on in vitro interactions between platelets and endothelial cells. Platelets from normal volunteers on a diet with (PLTSe+) or without (PLTSe-) selenium supplementation and human umbilical vein endothelial cells cultured in medium alone (ECSe-) or supplemented with Se (ECSe+) were used.

Cell-specific differences in the regulation of IL-6 expression by PMA.

We have studied the regulation of IL-6 expression in human blood monocytes and lymphocytes. LPS and IFN-gamma induced IL-6 gene expression with a similar qualitative profile in both cell types. Treatment of monocytes and lymphocytes with PMA resulted, instead, in different effects: monocytes accumulated IL-6 and its message, while lymphocytes were inhibited either in the absence or the presence of LPS and IFN-gamma.

Cell proliferation and death: morphological evidence during corticogenesis in the developing human brain.

Cell proliferation and death account for the refinement of the cell number during corticogenesis. These processes have been investigated in the human developing telencephalon (12th-24th week of gestation) and cerebellum (16th-24th week). Only foetal brains, which had normal neuropathological examination, were utilised.

Repression of the IL-6 gene is associated with hypermethylation.

The expression of the IL-6 gene is usually tightly controlled and may be induced in specific tissues after treatment with appropriate stimuli. Although much is known about the inducible expression of the IL-6 gene, the molecular mechanisms responsible for its repression in specific tissues or cell types remain poorly defined. To address this question we have studied two human breast carcinoma cell lines, MDA-MB-231, in which the IL-6 gene is expressed, and, MCF-7, in which the IL-6 message is undetectable by Northern blot assay even in the presence of inducers.

Cortical excitability in patients after loading doses of lamotrigine: a study with magnetic brain stimulation.

Purpose: Transcranial magnetic stimulation (TMS) of the brain allows the pharmacologic effects of anti-convulsant drugs (AEDs) on the excitability of motor corticospinal pathways to be evaluated in patients with epilepsy and normal subjects. However, no study has yet documented the changes in motor excitability in patients treated with lamotrigine (LTG). We aimed to study the effects of loading doses of LTG on TMS recordings in patients with epilepsy at the beginning of their treatment.

Transcranial magnetic stimulation selectively impairs interhemispheric transfer of visuo-motor information in humans.

We investigated the cerebral cortical route by which visual information reaches motor cortex when visual signals are used for manual responses. Subjects responded unimanually to photic stimuli delivered to the hemifield ipsilateral or contralateral to the moving hand. On some trials, trans-cranial magnetic stimulation (TMS) was applied unilaterally over the occiput, with the aim of stimulating extrastriate visual areas and thereby modifying transmission of visual input.

Protein synthesis inhibitors cycloheximide and anisomycin induce interleukin-6 gene expression and activate transcription factor NF-kappaB.

In two human cell lines, MDA-MB-231 and HeLa, the inducible expression of the interleukin-6 (IL-6) gene by two protein synthesis inhibitors, cycloheximide and anisomycin, was compared with the induction by the most potent physiological inducer of IL-6 described to date, interleukin-1beta (IL-1beta). In cycloheximide or anisomycin treated cells, the accumulation of the IL-6 message and the activation of transcription factors required for IL-6 gene expression occurs at an extent similar to that obtained with IL-1beta. Furthermore, IL-6 mRNA accumulation stimulated by cycloheximide or anisomycin is almost completely inhibited in the presence of actinomycin D, indicating that this effect occurs mainly through the activation of the transcriptional machinery.

T-cell-mediated epineurial vasculitis and humoral-mediated microangiopathy in cryoglobulinemic neuropathy.

We used immunohistochemistry to assess the role of humoral and cellular factors in endoneurial microangiopathy and epineurial vasculitis in 15 nerve biopsies of patients with axonal neuropathy and monoclonal or mixed cryoglobulinemia (CG). Deposition of immunoglobulins and cytolytic complement was detected in endoneurial capillaries of patients with mixed CG. Epineurial inflammatory infiltrates containing beta2-integrin-positive lymphocytes and monocytes surrounded arterioles expressing cell adhesion molecules, thus suggesting a cell-mediated pathogenesis of the epineurial vasculitis.

Quantitative study of ductal breast cancer progression. A progression index (P.I.) for premalignant lesions and in situ carcinoma.

The diagnostic subjective assessment of ductal premalignant proliferative lesions and in situ carcinoma of the breast produces unsatisfactory results. Since the phenotypical cell changes in tumour progression toward infiltrating cancer constitute a continuum, a grading on a continuous scale of values produces a more reliable and reproducible characterization. The diagnostic assessment for any individual patient may be expressed by a progression index (P.

Thumb-pointing is humans after damage to somatic sensory cortex.

Three patients with a severe somatosensory deficit consequent on damage of the right somatosensory cortices were required, while blindfolded, to point with their insensate thumb to select positions on the other left fingers. Given the absence of feedback, the motor performance of the insensate thumb appeared grossly impaired in all patients. However, all patients attained end-points with an accuracy greater than chance.

Heterogeneous response of individual multicellular tumour spheroids to immunotoxins and ricin toxin.

The cytoreductive effects of anti-transferrin receptor (anti-TfnR) immunotoxins (ITs) and of ricin toxin against tumour micromasses have been evaluated in a multicellular tumour spheroid (MTS) model. More than 600 (656) MTSs obtained with human breast carcinoma (MCF7) or rat glioblastoma (9L) cell lines were treated individually with ITs or toxin and the effects induced by the treatment were measured for each MTS as volume variation vs time by applying the Gompertz growth model. Two dose-dependent patterns of MTS growth were observed in MTSs of both cell lines in response to IT or toxin treatment: (1) complete inhibition of MTS growth ('sterilisation'); and (2) partial/complete inhibition ('heterogeneous response').

Clinical and therapeutic implications of chronic left ventricular dysfunction in coronary artery disease.

In patients with myocardial ischemia, left ventricular dysfunction (LV) may arise from irreversible damage (cell death), myocardial stunning (postischemic dysfunction), or myocardial hibernation (persistent myocardial dysfunction at rest due to underperfusion). Chronic LV dysfunction usually refers to hibernating myocardium. However, stunning might also become chronic, producing persistent myocardial dysfunction.

Quantitative study of ductal breast cancer progression. Morphometric evaluation of phenotypical changes occurring in benign and preinvasive epithelial lesions.

Fifty-nine cases of Breast Epithelial Proliferative Lesions (BEPL) and Ductal Carcinoma in Situ (DCIS), were studied by image analysis, to evaluate the nuclear changes occurring in the conventional diagnostic categories of ductal hyperplasia, atypical ductal hyperplasia and DCIS with quantitative methods. Diagnosis reproducibility is the main practical problem of these breast lesions. In fact, with subjective methods, the reproducibility appears to be very low and precarious especially for clinical demands.

Cyclosporin in Behçet's disease: results in 16 patients after 24 months of therapy.

The aim of this study was to evaluate the usefulness of cyclosporin in Behçet's disease. Sixteen subjects (10 males and 6 females; mean age 25.2 years) affected by the complete type of Behçet's syndrome received 5 mg/kg/day of cyclosporin for 24 months.

The efferent mechanisms of reflex hemodynamic responses to distension of the descending colon in anesthetized dogs.

We have recently shown that distension of the descending colon in anesthetized dogs causes reflex increases in heart rate, aortic blood pressure and the maximal rate of rise of left ventricular pressure, involving afferent pathways in the hypogastric nerves. In this study we have examined the efferent mechanisms involved in those responses. The descending colon was distended using Ringer solution at constant pressure in 13 anesthetized dogs.

Multimarker immunohistochemical staining of calgranulins, chloroacetate esterase, and S100 for simultaneous demonstration of inflammatory cells on paraffin sections.

Mac387 monoclonal antibody (MAb) recognizes two calcium binding, myeloid-associated proteins, now termed calgranulins, expressed at high levels by neutrophils and monocytes. Calgranulins are related to migration inhibitory factor (MIF) and are lost in a few days from monocytes differentiated in vitro. This marker is therefore potentially useful to analyze macrophage heterogeneity and turnover in tissue sections.

Effect of streptokinase on left ventricular modeling and function after myocardial infarction: the GISSI (Gruppo Italiano per lo Studio della Streptochinasi nell'Infarto Miocardico) Trial.

It has been shown that streptokinase administration at the time of acute myocardial infarction reduces mortality significantly, and that this reduction in mortality should be related to salvage of jeopardized myocardium and preservation of left ventricular function. To better define the relation between thrombolytic therapy and left ventricular modeling and function after acute myocardial infarction, 331 consecutive patients enrolled in the Gruppo Italiano per lo Studio della Streptochinasi nell'Infarto Miocardico trial were studied by two-dimensional echocardiography just before discharge from the hospital. A 6 month follow-up examination was also available in 232 of these patients.

Spatial distribution of the inhibitory effect of peripheral non-informative cues on simple reaction time to non-fixated visual targets.

It is known that reaction time (RT) for the detection of a light target at extrafoveal locations is lengthened by a previous non-informative light cue at the same location. We describe an additional inhibitory effect from cues remote from the target but occurring within the same lateral or altitudinal visual hemifield. Subjects made a speeded key-press response to the second of two successive light flashes in a pair while maintaining fixation.