Therapeutic strategies in weaning failure.
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Humans↗
Biomedical subjects
A Rossi
Publications and source records attributed to A Rossi.
Diastrophic dysplasia sulfate transporter (DTDST) gene is not involved in pseudodiastrophic dysplasia.
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Adolescent↗
A method for potentiating Renshaw cell activity in humans.
Owing to the introduction of a special electrophysiological method [3] it has been possible to study spinal recurrent inhibition in humans. The method, however, is indirect and, being based on an H reflex technique, can only be tested in motor nuclei from which a large monosynaptic response can be obtained. We have developed a complementary method by which pharmacological stimulation of Renshaw cells is obtained [6]. It exploits the central cholinergic properties of L-acetylcarnitine [18], a substance which most likely acts potentiating the synaptic drive of the motoneurone collaterals [7], known to be the main source of excitation of Renshaw cells [15,20]. The use of L-acetylcarnitine has allowed to establish the validity of the original methodology [6] and to confirm the presence of recurrent inhibition, tested either by the H reflex technique [11-13] or, if not possible, by the PSTH technique and/or rectified averaged EMG analysis [1,4], in many limb motor nuclei. Thus, it can be expected that L-acetylcarnitine may be used as an independent means for identifying changes in motoneuronal activity related or attributed to the influence of Renshaw cells.
Acetylcarnitine↗
Comparison of left ventricular function and volumes during transesophageal atrial pacing combined with two-dimensional echocardiography in patients with syndrome X, atherosclerotic coronary artery disease, and normal subjects.
Nine patients with syndrome X were compared with 2 groups of patients known to have coronary artery disease (CAD) (8 patients who developed regional wall motion abnormalities [group ECHO+] and 6 patients who showed only ST depression at echo-pacing [group ECG+]) and with 6 healthy volunteer control subjects. Left ventricular function at rest was normal in all patients. End-diastolic and end-systolic volumes (ml/m2) and ejection fraction were calculated at baseline and at peak of echo-pacing using a Simpson's biplane method. No regional wall motion abnormalities were observed during the echo-pacing in patients with syndrome X or in the volunteers. End-diastolic volume decreased in patients with syndrome X, in the volunteers (from 47 +/- 11 to 30 +/- 12 and from 72 +/- 7 to 38 +/- 6, respectively, p <0.01 for both), and in ECG+ patients (from 48 +/- 10 to 33 +/- 6, p <0.05), whereas it did not change in ECHO+ patients. End-systolic volume decreased in patients with syndrome X and in the volunteers (from 17 +/- 5 to 11 +/- 4 and from 28 +/- 6 to 16 +/- 4, respectively, p <0.01 for both), whereas it did not change or else slightly increased in patients with CAD (from 18 +/- 10 to 16 +/- 5 for ECG+ patients and from 19 +/- 5 to 24 +/- 9 for ECHO+ patients, p = NS for both), regardless of whether regional wall motion abnormalities appeared. Ejection fraction decreased in ECG+ and ECHO+ patients (from 64 +/- 12 to 52 +/- 11 and from 62 +/- 9 to 44 +/- 13, respectively, p <0.01 for both), whereas it did not change in patients with syndrome X and in the volunteers (from 64 +/- 8 to 61 +/- 8 and from 61 +/- 7 to 58 +/- 7, respectively, p = NS for both). During echo-pacing in syndrome X patients no regional wall motion was detected. Left ventricular volumes and ejection fraction showed the same patterns of variation in these patients as they did in the healthy control subjects, in contrast with those patients with CAD, whether or not regional wall motion abnormalities appeared in the latter.
Aged↗
Echocardiographic assessment of left ventricular remodeling: are left ventricular diameters suitable tools?
OBJECTIVES: We sought to analyze the value of echocardiographic left ventricular (LV) diameters in assessing LV remodeling. BACKGROUND: LV diameters are easily measured and commonly used as a substitute for volumetric analysis to evaluate LV remodeling caused by ventricular overload or dysfunction. However, the impact of these measurements on outcome is disputed, suggesting that they may not adequately assess LV remodeling. METHODS: M-mode echocardiographically measured LV dimensions and the derived LV ejection fraction and end-systolic wall stress were compared with LV volumes and the derived LV ejection fraction and wall stress using the biplane Simpson rule. These measurements were made prospectively and simultaneously in 463 patients (289 men, 174 women; mean [+/-SD] age 62 +/- 15 years), including 46 normal subjects, 52 with aortic regurgitation, 253 with mitral regurgitation and 112 with LV dysfunction. RESULTS: The correlation between diameter and volume was good at end-systole (r = 0.91, p < 0.0001) and end-diastole (r = 0.86, p < 0.0001). However, the relation was exponential, and the 95% confidence interval increased with increasing diameter. The calculated LV ejection fraction and wall stress using LV diameter and volume correlated linearly with a limited range of error (r = 0.96, SEE = 5%, p < 0.0001 and r = 0.95, SEE = 20 g/cm2, p < 0.0001, respectively). CONCLUSIONS: For assessing LV remodeling, LV diameters measured by M-mode echocardiography allow acceptable estimation of LV ejection fraction and wall stress and correlate significantly with LV volumes but are hindered by a wide range of error for assessment of LV size, especially for enlarged ventricles, suggesting that measurement of LV volume should be the preferred method of echocardiographically assessing LV remodeling.
Aortic Valve Insufficiency↗
Changes in Ib heteronymous inhibition to soleus motoneurones during cutaneous and muscle nociceptive stimulation in humans.
The effects of selective tonic cutaneous and muscle pain stimulation on heteronymous Ib pathways from the gastrocnemius medialis to the soleus motoneurones were studied in five healthy human subjects. Tonic pain stimulation, monitored by a psychophysical method, was obtained by local injection of 60 mg levo-ascorbic acid (L-AS) in a volume of 0.3 ml. Nociceptive cutaneous and muscle stimulation of the dorsal foot produced opposite, long-lasting changes in heteronymous Ib pathways to soleus motoneurones: Ib facilitation during cutaneous stimulation was reversed by disinhibition during muscle stimulation. The time-course of these Ib changes strictly paralleled that of subjective pain sensation. On the contrary, when the same nociceptive stimuli were applied to the leg (at pretibial level), the differences between cutaneous and muscle pain disappeared and similar short-lasting phases of facilitation and inhibition of Ib activity were observed. It is concluded that tonic discharge of cutaneous and muscle nociceptive afferents arising from the foot have specific and opposite effects on Ib inhibitory pathways to ankle extensor motoneurones. These interactions between muscle and cutaneous nociceptive and Ib pathways may be used to change muscle synergies, thus contributing to the establishment of appropriate adaptive locomotor strategies during pain.
Adult↗
Association between striatal reduction and poor Wisconsin card sorting test performance in patients with schizophrenia.
Several findings support the hypothesis that the striatum is implicated in executive functions and in the modulation of goal-directed behavior, and could play a key role in the pathophysiology and in the production of symptoms and signs in schizophrenia. We have studied the relationship between the objective measures of the striatal structures, as evaluated by magnetic resonance imaging (MRI), and the Wisconsin Card Sorting Test (WCST) performance in a schizophrenic sample. Thirty-five schizophrenic patients underwent MRI scans of striatal structure and neuropsychological evaluation of executive functions by WCST. Poor WCST performers had a reduction of the left caudate nucleus and putamen, and right total striatum when compared to 24 healthy controls. Significant correlation coefficients were also observed between neuropsychological indexes and left striatal measures. The findings suggest the existence of a relationship between abnormalities of striatal structure and abnormal executive-type or organizational cognitive functions.
Adult↗
Is Wisconsin Card Sorting Test performance related to 'working memory' capacity?
The Wisconsin Card Sorting Test (WCST) is a multifactorial and complex test, and it involves so many different kinds of functions that it is difficult to understand why patients fail. Capacity of 'working memory' is possibly involved in the WCST performance and is considered a relevant factor responsible for the schizophrenics' poor performance. The present study was specifically designed to assess the relationship between 'working memory' measurements and WCST performances of schizophrenics. Furthermore, we investigated the relationship between the cognitive dysfunction and the clinical symptomatology. The following tests were administered to 30 schizophrenics and 25 healthy subjects: WCST, Digit Span Test (Backward and Forward), Digit Symbol Substitution Test and Visuo-Spatial 'working memory' Test, a card test appropriately devised. Clinical assessment included the Italian version of the scale of Krawiecka Manchester Scale (K-MS) and the Outcome scale by Strauss and Carpenter (1972). The 30 patients differed significantly in all the neuropsychological variables from the controls. WCST indexes did not correlate significantly with any of the 'working memory' measures (visuo-spatial and verbal) in the samples studied. No relationship was seen between the neuropsychological performances and clinical symptomatology as evaluated by the K-MS scale. WCST indexes and DSST significantly correlated with the outcome measure. The results do not support the hypothesis that executive dysfunction as evaluated by WCST is attributed to 'working memory' impairment, rather they could suggest that these two neuropsychological functions identify different neurocognitive constructs.
Adult↗
Sexual behavior and hemispheric laterality of the focus in patients with temporal lobe epilepsy.
Various studies have described an unusually common incidence of sexual and reproductive dysfunction in patients affected by temporal lobe epilepsy (TLE). The purpose of the present study was to further investigate, by means of an ad hoc questionnaire, the relationship between sexual disorders and the hemispheric laterality of the epileptic focus in men and women with right (R) TLE and left (L) TLE. The results suggest a reduction of sexual interest in patients with R-TLE as compared with L-TLE in both men and women. This effect was fundamentally observed when sexual interest was implicitly explored. No significant difference was found between R-TLE and L-TLE groups concerning most aspects of sexual performance. Various hypotheses are discussed to interpret this effect of hemispheric lateralization on sexual interest.
Adult↗
Undersulfation of cartilage proteoglycans ex vivo and increased contribution of amino acid sulfur to sulfation in vitro in McAlister dysplasia/atelosteogenesis type 2.
Mutations in the diastrophic dysplasia sulfate transporter gene cause a family of chondrodysplasias including, in order of increasing severity, diastrophic dysplasia, atelosteogenesis type 2 and achondrogenesis type 1B. McAlister dysplasia is a lethal chondrodysplasia considered on the basis of minor radiographic features to be a disorder different from atelosteogenesis type 2. Here, we demonstrate that McAlister dysplasia arises from mutations in the diastrophic dysplasia sulfate transporter gene and that this disorder essentially coincides on molecular and biochemical grounds with atelosteogenesis type 2. The fetus affected by McAlister dysplasia we have studied is a compound heterozygote for mutations leading to R279W and N425D substitutions in the diastrophic dysplasia sulfate transporter. Proteoglycan sulfation was studied in epiphyseal cartilage and in chondrocyte cultures of the patient by high performance liquid chromatography of chondrotinase digested proteoglycans; a high amount of non-sulfated disaccharide was observed as a consequence of the alteration of the transporter function caused by the mutations. However, sulfated disaccharides were detectable even if in low amounts, both in cultured cells and tissue. Functional impairment of the sulfate transporter was demonstrated in vitro by reduced incorporation of [35S]sulfate relative to [3H]glucosamine in proteoglycans synthesized by chondrocytes and by sulfate-uptake assays in fibroblasts. Parallel in vitro studies in a patient with achondrogenesis 1B indicated that the severity of the clinical phenotype seems to be correlated to the residual activity of the sulfate transporter. The capacity of fibroblasts to use cysteine as an alternative source of sulfate was evaluated by double-labeling experiments. Relative incorporation of [35S]cysteine-derived sulfate in the glycosaminoglycan chains was increased in the patient's cells, indicating that, in vitro, the catabolism of sulfur-containing amino acids can partially compensate for intracellular sulfate deficiency. Residual sulfation observed in proteoglycans extracted from cartilage suggests that this mechanism may be operating also in vivo.
Anion Transport Proteins↗
No deficit in Wisconsin Card Sorting Test performance of schizophrenic patients' first-degree relatives.
The Wisconsin Card Sorting Test (WCST) was administered to 92 schizophrenic patients, 25 first-degree relatives and 60 normal subjects in order to investigate whether this task could be considered a trait marker of vulnerability to schizophrenia. The schizophrenic patients performed significantly worse than either their relatives or normal subjects, but unaffected relatives did not differ from controls. Our results suggest that WCST performance is more likely a feature inherent to the disease process rather than an index of the genetic susceptibility to the illness.
Adult↗
The sequence of palF, an environmental pH response gene in Aspergillus nidulans.
To molecularly characterize the influence of external pH in the secretion of enzymes by filamentous fungi, we have cloned and sequenced the palF gene of Aspergillus nidulans (An). An An wild-type (wt) chromosome VII-specific cosmid library was used to transform a palF15 mutant strain. Selection for complementation was done on medium containing beta-glycerolphosphate as the sole Pi source. Two cosmids were identified (W2G08 and W4G12) and further subcloning of one cosmid (W2G08) defined a 5-kb PstI genomic fragment, which fully complements the palF15 mutation. An internal fragment from the genomic clone recognized a single message of approx. 3.5 kb on Northern blot. cDNA clones were obtained from a lambda gt10 cDNA library and sequenced, showing a nucleotide (nt) sequence of 3311 base pairs (bp), with a 828 bp long 5'-untranslated region (UTR). The major open reading frame (ORF) identified in the sequence codes for a putative 775 amino acid (aa) protein, which shares some similarity with two putative ORF products of Saccharomyces cerevisiae (Sc).
Amino Acid Sequence↗
Opposite effects of the remodeling of infarcted and non-infarcted myocardium on left ventricular function early after infarction in humans. An echocardiographic study in patients examined before and after myocardial infarction.
OBJECTIVE: The purpose of this study was to evaluate infarction-related changes in the infarcted and the non-infarcted myocardium using a baseline assessment of ventricular function obtained prior to the infarction. BACKGROUND: Experimental studies have shown that both infarcted and non-infarcted myocardium contribute to the process of left ventricular dilatation soon after the infarction, but no data exist on the effect that the infarct has on the pre-infarct ventricular morphology in humans. METHODS AND RESULTS: 10 patients, out of 721 admitted to our coronary care unit with a first acute myocardial infarction over a 3-year period, had had an echocardiographic examination performed before (354 +/- 407 days) and after (10 +/- 9 days) the infarction which were adequate for quantitative evaluation. Ventricular volume (Simpson) and regional wall motion (Centerline method) were evaluated by biplane apical sections and the endocardial length of the infarct and the non-infarct segments, imaged in a cross-sectional view at the papillary muscle level, were measured. After the infarction end-diastolic and end-systolic ventricular volume increased (P = 0.0003 and P < 0.0001, respectively); diastolic and systolic infarct segment length increased (P = 0.011 and P = 0.0008, respectively), while non-infarct segment had only diastolic lengthening (P = 0.019), without systolic changes. The ejection fraction decreased after the infarction (P < 0.0001), in inverse relation to infarct size and in direct relation to diastolic non-infarct segment lengthening. In the five patients in whom there was a significant diastolic lengthening of non-infarct segment (larger than mean +/- 2 S.D. of the interobserver variability) the decrease in ejection fraction was less than in the patients without significant lengthening of this segment (P = 0.017), despite a similar echocardiographic infarct size index. CONCLUSION: Ventricular enlargement early after myocardial infarction is due to both infarct expansion and lengthening of non-infarct segment. However, while systolic stretching of the infarct segment is a deleterious process that accounts for the increase in end-systolic volume, diastolic non-infarct segment lengthening is the expression of a functional compensatory mechanism that counteracts the reduction of the ventricular pump function secondary to the infarction.
Aged↗
Stability of type I collagen CNBr peptide trimers.
As indices of triple helix stability of type I collagen CNBr peptide homotrimers, deltaG degrees for monomer-trimer transitions and melting temperatures were obtained from circular dichroism measurements at increasing temperatures. The data were compared with the stability of the parent native molecule. Peptides were found to have a lower stability than the whole collagen molecule. The general implication is that the coordinated water molecules play a key role in determining collagen triple helical stability and high cooperativity at melting. Other factors (monomer stability, ionic and hydrophobic factors, variations of composition, specific sequences) could also contribute towards peptide stability; these factors could explain the data obtained in the case of peptide alpha1(I) CB3.
Collagen↗
The genes encoding geranylgeranyl transferase alpha-subunit and transglutaminase 1 are very closely linked but not functionally related in terminally differentiating keratinocytes.
We report here the entire exon/intron structure of the gene encoding the alpha-subunit of human Rab geranylgeranyl transferase (RABGGTA) gene, which is positioned in a tandem head-to-tail arrangement with the transglutaminase 1 (TGM1) gene, and its polyadenylation signal sequence is located just 2.3 kbp upstream of the capsite of TGM1. Even though TGM1 and RABGGTA have different functions, their close localization raised the question as to whether they are functionally related in the epidermis. To address this question, we have studied the expression of the two genes by RT-PCR in normal human epidermal keratinocytes cultured under various differentiation conditions. While the expression of the TGM1 gene is markedly affected by the calcium concentration of the medium, all trans retinoic acid, vitamin D3, and TPA treatment, the expression of the RABGGTA gene was unaffected by these reagents. Taken together, even though these two genes are unusually closely linked, they are not functionally related in the terminal differentiation program of epidermal keratinocytes.
Alkyl and Aryl Transferases↗
Apparent absence of aging and gender effects on serotonin 1A receptors in human neocortex and hippocampus.
The effects of gender, aging and gender x age on the binding of the 5-HT1A receptor high-affinity agonist [3H]8-hydroxy-2(di-N-propylamino)tetralin ([3H]8-OH-DPAT), were evaluated and compared in tissues of human prefrontal, temporal, parietal, occipital cortex and hippocampus obtained from 21 autopsy subjects. The results revealed no variation with age or gender in either the [3H]8-OH-DPAT maximum binding capacity (Bmax) or dissociation constant (Kd) values. On the other hand, when separate correlations to subject ages were performed for men and women, aging effects on [3H]8-OH-DPAT Bmax and Kd were detected: in men, a significant age-dependent decrease in Kd values was observed in the occipital cortex; in women, the Bmax significantly decreased with aging in the parietal cortex and hippocampus, while increasing in occipito-cortical membranes. Overall, the present study reveals that, although neither gender nor aging 'per se' seem to modify the 5-HT1A receptor binding, gender may reveal region-specific aging effects, i.e. on receptor affinity in men and receptor density in women. Such findings should stimulate further investigation on the hypothesized existence of gender x age-related cross-connections between serotonergic system and hypothalamus-pituitary-gonadal circuits.
Adult↗
Wisconsin card sorting test and Stroop test performance in schizophrenia: a shared construct.
The Wisconsin card sorting test (WCST) and Stroop test were administered to 25 schizophrenic patients in order to better identify and understand more specific processing mechanisms involved in executive dysfunctions and to investigate their hypothetical involvement in symptom formation. Data show that for as much as the two tests employed measured executive functions in terms of mental control and cognitive flexibility, our findings seemed to indicate shared or interconnected mechanisms. No correlations were seen between the psychopathological evaluation and any of the neuropsychological indexes. The use of the Stroop task could provide a more readily cognitive analysis in terms of specific processing mechanisms, at the basis of WCST impairment in schizophrenia.
Adult↗
Recurrent inhibition between motor nuclei innervating opposing wrist muscles in the human upper limb.
1. Effects of conditioning motor volleys of increasing amplitude on antagonistic motor nuclei were tested at the wrist and elbow level in man. 2. The modifications of biceps, triceps, flexor carpi radialis (FCR) and extensor carpi radialis (ECR) motoneurone excitability were tested both in post-stimulus time histogram (PSTH) and rectified averaged EMG experiments. 3. Conditioning motor volleys were evoked in biceps, triceps, FCR and ECR muscles by electrical stimuli applied to the corresponding nerves. The intensity of the conditioning stimuli was systematically varied from an intensity just below motor threshold to one giving rise to a motor response equal to half of the maximal direct motor response (Mmax). 4. The effect of the injection of a cholinergist agonist, L-acetylcarnitine (L-Ac), on antagonistic conditioning motor volleys was tested for each motor nucleus. 5. Results obtained at the wrist and elbow level were strikingly different. Antagonistic motor volleys resulted in an early and long-lasting inhibition enhanced by L-Ac injection in wrist motor nuclei, while no modification was observed in elbow motor nuclei. 6. The characteristics of the early and long-lasting inhibition evoked in wrist motor nuclei by antagonistic motor volleys suggest that they are due to the activation of Renshaw cells by the conditioning motor volleys. 7. It is therefore concluded that these experiments provide further evidence that the interconnections between motoneurones, interneurones mediating reciprocal inhibition and Renshaw cells at the wrist level are different from those described elsewhere. Indeed, it has already been shown that the interneurones mediating reciprocal inhibition between FCR and ECR are not inhibited by Renshaw cells, and the results presented here suggest that FCR-coupled Renshaw cells inhibit ECR motoneurones and vice versa.
Adult↗