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Biomedical subjects

M Nobile

Publications and source records attributed to M Nobile.

At least 73 records · Page 4Linked to original sources
PubMed1993

Distribution of a novel mutation in the first exon of the human dopamine D4 receptor gene in psychotic patients.

Disturbances in dopaminergic transmission have been implicated in the etiology of psychotic disorders. Interindividual differences in deoxyribonucleic acid (DNA) sequences coding for dopamine receptor proteins might contribute to the genetic background of these diseases. We have identified a variation in exon 1 of the dopamine D4 receptor (DRD4) gene, which is characterized by a polymorphic 12 base pair (bp) repeat. This repeat codes for a sequence of four amino acids in the extracellular N-terminal part of the receptor, which borders the first putative transmembrane domain. The 12bp repeat occurs as a two-fold repeat in the more common variant (A1 allele) and is represented only once in the rarer one (A2 allele). The frequency of this DNA polymorphism was determined in a sample of 59 patients suffering from delusional disorder, in 79 schizophrenic patients, and in 75 control subjects. Sixteen (27%) of the 59 patients with delusional disorder carried the A2 allele compared with six (8%) of the controls. The observed difference in genotype frequencies between patients with delusional disorder and controls was highly significant. There were no significant differences in genotype frequencies between schizophrenics and controls: Our results strongly suggest the involvement of genetic variation in the DRD4 gene in conferring susceptibility to delusional disorder.

Adult↗
PubMed1993

Possible link between vitamin D and hyperoxaluria in patients with renal stone disease.

1. Vitamin D seems to play an essential role in the pathogenesis of idiopathic hypercalciuria at least in part via intestinal hyperabsorption of calcium. Hyperabsorption of calcium, in turn, might enhance the intestinal uptake of free oxalate, thus leading to hyperoxaluria. To verify this hypothesis we studied 75 calcium-stone-formers subdivided as follows: group 1 (15 patients) with isolated hyperoxaluria; group 2 (25 patients) with hyperoxaluria and hypercalciuria; group 3 (22 patients) with isolated hypercalciuria; group 4 (12 patients) with no metabolic abnormalities. 2. As expected, urinary calcium excretion differed in the various groups (P < 0.001), being highest in groups 2 and 3; urinary oxalate excretion, by definition highest in groups 1 and 2, was even more pronounced in group 2 than in group 1 (P < 0.05). Although in the normal range, the serum 1,25-dihydroxyvitamin D concentration was higher (P < 0.001) in the two hypercalciuric groups (2 and 3), showing peak levels in group 2. 3. When the data from the 75 stone-formers were pooled, there was a positive correlation between the serum concentration of 1,25-dihydroxyvitamin D and urinary calcium excretion (P < 0.001) and urinary oxalate excretion (P < 0.003), the latter relationship also being present when only the two hypercalciuric groups (groups 2 and 3) were considered together (P < 0.05). 4. Our data seem to confirm a relevant role for the vitamin D system in the pathogenesis of calcium nephrolithiasis due to increased intestinal calcium absorption, but also because this in turn induces a greater intestinal absorption of oxalate, thus leading to the occurrence or exacerbation of hyperoxaluria.

Adult↗
PubMed1993

Delusional disorder and mood disorder: can they coexist?

DSM III-R acknowledges that delusional disorder and mood disturbance can coexist. The aim of the study is to analyze mood disturbances occurring within a delusional disorder. An external validator, as the increased familial risk of psychiatric disorder, is also added to clarify the relationship between the two diagnostic areas. We found a high frequency of mood disturbances in our patients (50.7%). We were able to identify a proportion of delusional patients affected by a recurrent form of mood disturbance (35.2%); in about 42% of these patients the onset of the mood disturbance preceded the onset of the delusional disorder by a considerable interval of time. Our hypothesis is that, in these cases, the observed mood disturbance could represent a codiagnosis of true mood disorder. This hypothesis is partly supported by familial data.

Adult↗
PubMed1992

Anionic currents of chick sensory neurons are affected by a phospholipase A2 purified from the venom of the taipan snake.

A neurotoxic phospholipase A2 was purified from the venom of the taipan snake Oxyuranus scutellatus scutellatus by three consecutive chromatographic steps on ion exchange resins, followed by an affinity column prepared with a phosphatidylcholine derivative attached to Sepharose. The phospholipase was shown to be of type A2 (specific activity of 85 units/mg protein), and an apparent molecular weight of 16,000. Amino acid analysis shows the presence of approx. 150 residues with the N-terminal amino acid sequence: NLAQFGFMIRCANGGSRSALDYADYGC, different from all the phospholipases described until now. This enzyme is lethal to experimental mice (LD50 = 10 micrograms/20 g mouse weight) and affects ionic currents in chick (Gallus domesticus) dorsal root ganglion cells, measured by the whole-cell clamp technique. In symmetrical external/internal ionic solutions, after suppression of Na+, K+ and Ca2+ currents, external application of phospholipase at a low concentration (30 nM) was shown to increase the baseline current in a reversible manner. The augmented response was voltage-dependent and the effect was much greater for negative currents. In the presence of a salt gradient across the membrane (out 40 mM NaCl/in 140 mM CsCl), the current reversal potential revealed a shift in the positive direction typically due to Cl- ion flux through the membrane. External application of a 50 microM concentration of picrotoxin caused a reversible reduction of the phospholipase-induced chloride current. Moreover, no appreciable current block was detected after addition of 50 microM DIDS.

Amino Acid Sequence↗
PubMed1992

K+ channels in PC12 cells are affected by propofol.

The effect on K+ currents (IK) of the general anaesthetic propofol (PR) (2,6-diisopropylphenol) was tested in undifferentiated clonal pheochromocytoma (PC 12) cells using the patch-clamp technique in whole-cell and single-channel configurations. PR decreased macroscopic IK amplitudes in a concentration-dependent way from 50 microM to 1 mM. The blocking effect was unchanged by repetitive depolarizing pulses and it was independent of the holding potential. Whereas activation of IK in control conditions was fitted by sigmoidal plus exponential time courses, only the sigmoidal time course gave an adequate fit with PR in the bath. The above effects were reversible. PR concentrations below 140 microM decreased single-channel activity for K+ channels with unitary conductance of 22 pS, in the voltage range between -40 and 60 mV from a holding potential of -50 mV. In contrast, the anaesthetic had nearly no effect on the opening probability of a channel with conductance of 10 pS. The unitary current amplitudes were unaffected in both channel types. These results suggest that PR action on IK may depend on the different blocking mechanisms of the K+ channels.

Animals↗
PubMed1992

Use of polymerase chain reaction nad denaturing gradient gel electrophoresis to identify polymorphisms in three exons of dopamine D2 receptor gene in schizophrenic and delusional patients.

The dopamine D2 receptor gene is a candidate gene for schizophrenia. We screened three exons of this gene for mutations in a large sample of schizophrenics, delusional patients and healthy controls. No structural changes were found, thus suggesting that psychopathology is not related to DNA alterations in the DRD2 gene.

Adult↗
PubMed1990

Clinical relevance of immunocytochemical detection of multidrug-resistance-associated P-glycoprotein in hematologic malignancies.

P-glycoprotein (P-170) is the phenotypic marker of tumoral cells that show the phenomenon of multidrug resistance (MDR). Using an immunocytochemical approach, we employed the monoclonal antibody C219 (which recognizes an epitope of such a glycoprotein) to evaluate in cytologic samples the expression of P-170 on neoplastic cells from 52 patients affected by different hematologic malignancies and its eventual correlation to clinical outcome. Longitudinal studies were also performed in 14 patients. Results obtained demonstrated that a) the so-called "MDR phenotype" may be heterogeneously represented (from less than 1 to 100% of positive cells) in hemopoietic tumors at diagnosis (without exposure to pharmacologic agents), as well as during the course of the disease, although a more substantial presence of P-170 occurred in treated patients. There was no correlation between neoplastic kinetic activity (such as expression of Ki 67 recognized nuclear proliferation-associated antigen) and P-170-positive cells. b) Percentage of positive cells as well as intensity of staining seemed to be important in determining MDR; in general, there was a strong correlation between expression of P-170 in more than 20% of neoplastic cells and a lack of response to chemotherapy. However, some false-positive and false-negative cases were observed. c) The detection of scattered P-170-positive cells may predict a pharmacologic selection of intrinsic or mutant-resistant clones.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1990

Temperature sensitivity of Ca currents in chick sensory neurones.

We have investigated the effects of temperature on the Ca currents of chick sensory neurones. Raising the temperature from 17 to 37 degrees C, caused low-threshold (LVA, T) and high-threshold (HVA, L and N) Ca currents to show a marked amplitude increase and a drastic acceleration of their activation-inactivation gatings. Compared to HVA channels, the LVA type showed a weaker temperature sensitivity. Its average Q10 values were closer to those of other voltage-operated ion channels: 1.7 (permeability), 1.9 (activation) and 2.2 (inactivation). Alternatively, the activation kinetics and peak permeability of HVA Ca channels showed maximal Q10 values of about 5 and 2.8, respectively. HVA channel deactivation was less sensitive to temperature (Q10 1.8). Inactivation of these channels was slow and monoexponential between 17 and 22 degrees C, but faster and double exponential above 30 degrees C, uncovering a fast temperature-sensitive decaying phase. The size and rate of decay of this component decreased with increasing membrane depolarizations and persisted at holding potentials positive to -80 mV, suggesting the involvement of temperature-sensitive Ca-mediated processes in the mechanism of HVA channel inactivation. Our data are consistent with the view that heating from 17 to 37 degrees C causes both an increased probability of Ca channels to open and a drastic acceleration of their activation-inactivation kinetics.

Animals↗
PubMed1989

A class of non-selective cation channels in human fibroblasts.

Non-selective cation channels were detected in membrane patches of cultured human fibroblasts. The channels had a unitary conductance which ranged from 14 to 25 pS in symmetrical 130 mM NaCl and were permeable to both sodium and potassium ions. Open channel probability was dependent either on the membrane potential and the Ca2+ concentration on the intracellular side of the membrane. High Ca2+ concentrations in the millimolar range were needed to keep the channel active.

Calcium↗
PubMed1988

A large conductance Cl- channel revealed by patch-recordings in human fibroblasts.

A Cl- channel with large single-unit conductance and characteristic voltage-dependent inactivation was studied on cultured human fibroblasts. The channel was activated only after excision and lasting depolarization of the membrane patch. In inside-out configuration and in symmetrical 135 mM NaCl, the conductance was 300 pS. The channel was usually open at the membrane potentials between -20 to +20 mV, while more negative or positive voltages closed the channel. The time course of this apparent inactivation process was dependent on increasing potential. Recovery from inactivation was made possible by returning the membrane potential to 0 mV. The channel was selective to Cl- over Na+ with a PCl/PNa of 6. The order of permeability among anions was: I greater than Br = Cl greater than isethionate greater than F greater than glutamate. The channel was blocked by internal application of a derivative of the diphenylamine-2-carboxilate (Blocker 144) but not by 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid.

Chlorides↗
PubMed1988

Significance and limits of cerebrospinal fluid beta-2-microglobulin measurement in course of acute lymphoblastic leukemia.

Cerebrospinal fluid beta-2-microglobulin (CSF-beta 2m) was measured longitudinally in 48 patients affected by acute lymphoblastic leukemia (ALL). Thirteen developed a central nervous system (CNS) involvement during the course of the disease; although moderately higher mean CSF-beta 2m levels were found in these subjects, no significant statistical differences were observed in comparison with patients without this complication and compared with the control group. No correlations were found between beta 2m and other biochemical parameters in CSF. Furthermore, CSF-beta 2m levels appeared to be influenced by previous combined chemoradiotherapeutic treatment for CNS prophylaxis, presence of meningeal non-neoplastic infiltrates, patients' ages, amount of CSF blasts, and their immunological phenotype. In particular, only clearly B-committed leukemic cells, when tested, showed a strong surface expression of beta 2m, as demonstrated by immunocytochemical detection of this protein on cell membrane. However, in specific cases, CSF beta 2m measurement and CSF/serum beta 2m ratio were helpful in diagnosing and monitoring isolated CNS disease. Such findings suggest that CSF-beta 2m assay may be a useful tool in the management of CNS involvement in the course of ALL in only selected patients, as several factors can modify the outcome.

Adult↗
PubMed1988

Low Ca2+-sensitive maxi-K+ channels in human cultured fibroblasts.

The patch clamp technique was used to reveal single channel activity in the membrane of human cultured fibroblasts. The most frequently detected ion channel type was a Ca2+-dependent K+ channel with a conductance of 287 +/- 38 pS in symmetrical 130 mM KCl. The channel showed a peculiar low Ca2+-sensitivity compared to that of similar channels in other preparations. In fact micromolar values of internal Ca2+ were not effective in the channel activation, except at high depolarizing membrane potentials. The activity was highly increased only when the channel was exposed to relatively high internal Ca2+ concentrations (0.2-2.0 mM).

Calcium↗