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Biomedical subjects

A Mele

Publications and source records attributed to A Mele.

At least 109 records · Page 6Linked to original sources
PubMed1996

Time-related effects of stress on cholinergic sensitivity.

The effect of the administration of the muscarinic cholinergic agonist oxotremorine on locomotor activity was investigated in DBA/2 mice subjected to chronic restraint stress of different durations (120 min daily for 10, 14 or 18 days). Oxotremorine induced a depressant effect on locomotion, which was reduced after 10 and 14 days of restraint, but not after a 18-day restraint stress. Acetylcholine (ACh) content was significantly reduced in prefrontal cortex after 10 and 14 days of stress but returned to control values after 18 days of restraint. No changes in ACh content were observed in nucleus accumbens and striatum. These results are discussed in terms of possible changes in muscarinic receptor sensitivity.

Acetylcholine↗
PubMed1996

Expression and characterization of a mouse/human chimeric antibody specific for EGF receptor.

Murine antibodies which recognize the epidermal growth factor receptor (EGF-r) are good candidates for therapy and diagnosis of tumors overexpressing this receptor. Here we report the isolation of the variable regions from a murine monoclonal antibody anti-EGF-r (Mint5), the procedure to obtain the mouse/human chimeric antibody (chMint5) and its expression in COS, NS0 and CHO cells. The approach followed to construct chMint5 is based on the use of consensus primers specific for the ends of the variable regions. The sequence imposed by the primers did not affect the targeting potential of the antibody. In fact, the affinity of the chimeric antibody for EGF-r was nearly the same as that of the parental murine antibody. Based on previous in vitro and in vivo animal studies. Mint5 was shown to be a good candidate for the targeting of EGF-r overexpressing tumours. chMint5 is expected to be less immunogenic than murine antibody and therefore, could be useful for human treatment.

Amino Acid Sequence↗
PubMed1996

Clavin, a type-1 ribosome-inactivating protein from Aspergillus clavatus IFO 8605. cDNA isolation, heterologous expression, biochemical and biological characterization of the recombinant protein.

We describe the cloning and expression of a new cDNA from the filamentous fungus Aspergillus clavatus IFO 8605. This cDNA contains an open reading frame (ORF) that predicts a putative ribonuclease precursor with high similarity to the alpha-sarcin family of ribosome-inactivating proteins (RIPs). The cDNA encoding the mature protein was expressed in Escherichia coli, and the recombinant protein, a 17-kDa polypeptide designated clavin was purified and characterized. Clavin shows typical type-1 RIP properties: specific cleavage of ribosomal and synthetic RNA and inhibition of protein synthesis in cell-free and cellular systems. When selectively targeted to a tumour cell antigen by coupling to a monoclonal antibody (mAb) clavin was able to inhibit protein synthesis at nanomolar concentration. Pharmacokinetics analysis in mice indicated an elimination half-life (t1/2 beta) of 7.4 h with no particular accumulation in major organs. Liver toxicity was very limited and transient while no alteration of kidney function was observed. Clavin induced a late and very low antibody response in mice. The in vitro and in vivo biological characteristics of clavin, together with its availability in large amounts, suggest the usefulness of this toxin in the production of toxic chemical conjugates.

Amino Acid Sequence↗
PubMed1996

Dopamine-N-methyl-D-aspartate interactions in the modulation of locomotor activity and memory consolidation in mice.

This study explores the functional interaction between glutamatergic and dopaminergic systems in the modulation of two behavioral responses: locomotor activity and memory consolidation assessed with one-trial inhibitory avoidance. In agreement with previous reports, the NMDA receptor antagonist, (+)-MK-801 ((+)-5-methyl-10,11-dihydro(a,d) cyclohepten-5,10-imine hydrogen maleate), dose dependently enhanced locomotor activity in mice. The selective dopamine D1 receptor antagonist SCH 23390 at doses up to 0.05 mg/kg was unable to affect MK-801-induced locomotor activity, while (-)-sulpiride, but only at high doses (30 mg/kg), and haloperidol (0.05 mg/kg) blocked the MK-801 effect. Hypermotility induced by MK-801 was enhanced by repeated administration of haloperidol (once daily administration for 14 days of 4 mg/kg) or (-)-sulpiride (125 mg/kg), but not SCH 23390 (0.5 mg/kg). Dopamine D1 (SKF 38393)- and D2 (quinpirole)-selective agonists enhanced retention of one-trial inhibitory avoidance performance whilst NMDA receptor antagonists 3-(2-D-carboxypiperazin-4-yl)propyl-1-phosphoric acid (CPP) and MK-801 impaired it. Moreover we observed that the NMDA receptor antagonist-induced impairment of memory consolidation was attenuated by subeffective doses of SKF 38393 (5 mg/kg) and quinpirole (0.25 mg/kg). Impairment of the response induced by post-trial injections of CPP and MK-801, in the one-trial inhibitory avoidance test, was highly enhanced by 14 days of daily administration of haloperidol (4 mg/kg), sulpiride (25 mg/kg) but also SCH 23390 (0.5 mg/kg). These results suggest that different neural mechanisms underlie the functional interaction between the two neural systems in the modulation of these behavioral responses. Further, the results of the chronic study revealed a possible heterologous regulation of NMDA receptors.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1996

Risk factors for essential thrombocythemia: A case-control study. Italian Leukemia Study Group.

BACKGROUND: Very little information is presently available regarding risk factors for essential thrombocythemia (ET). METHODS: A case-control study was performed to study the possible association between ET and selected behavioral, occupational, and environmental exposures. RESULTS: Thirty-nine patients aged 20 years or older and 156 controls were enrolled in 2 Italian Hematology Departments located in Rome and Pavia. Controls were recruited among outpatients seen in the same hospitals and matched 4:1 to the patients after stratification by age and sex. Odds ratio (OR) estimates suggest an association between ET and hair dye use (in particular the use of dark hair dye for periods longer than 10 years: OR - 5.3; 95% confidence interval [CI], 1.4-19.9), living in houses built with tuff (a material with a high concentration of gamma-emitting radionuclides and radon) for longer than 9 years (OR = 5.1; 95% CI, 1.2-22.1), and selected occupations (electrical worker and shoemaker, OR +infinity and 2.7; 95% CI, 0.5-16 respectively). CONCLUSION: Behavioral exposures such as hair dyes, living in a tuff house, and working as an electrician are significantly associated with ET development. The data are consistent with those observed in acute leukemias.

Adult↗
PubMed1996

Amygdala lesions block the effect of cocaine on memory in mice.

Post-training cocaine intraperitoneal administration enhanced memory consolidation in unoperated and sham-lesioned mice tested in a one-trial inhibitory avoidance task. Bilateral electrolytical amygdala lesions blocked this effect. The results are interpreted in terms of involvement of neurotransmitter, and in particular dopaminergic, systems in the effects of cocaine on memory.

Amygdala↗
PubMed1996

Efficiency of different viral promoters in directing gene expression in mammalian cells: effect of 3'-untranslated sequences.

We compared (i) the enhancer/promoter (mCMV promoter) from the murine cytomegalovirus (CMV) major immediate early gene,(ii) the enhancer/promoter from human CMV major immediate early gene, containing a short promoter (h1CMV) or a long stretch of 5' untranslated region (UTR) from the gene promoter (h2CMV) and (iii) the simian virus 40 (SV40) enhancer/early region promoter (SV2) for their ability to direct foreign gene expression in transiently transfected mammalian cell lines. Two series of recombinant plasmids containing the different viral promoters fused to the cat reporter gene and 3'-UTR for processing of transcripts from either the SV40 early region or the rabbit Beta 1-globin-encoding gene (Glb) were also analyzed for their effect on transient gene expression. The mCMV was the most active in dihydrofolate reductase-deficient Chinese hamster ovary (CHOdhfr-) cells and BALB/3T3 clone A31 mouse embryo cells. The h2CMV was more active than the other promoters in Bowes human melanoma cells and in Vero African green monkey kidney cells. In human hepatoma (Hep G2) cells, similar levels of CAT synthesis were observed with the h2CMV- and the mCMV-based vectors. In Hep G2 and Bowes cells, 3'-UTR from the SV40 early region resulted in consistently higher levels of cat expression, as compared to the rabbit beta 1-Glb gene, while the converse was true in BALB/3T3 clone A31 and Vero cells. SV40 early region and rabbit beta1-Glb gene 3'-UTR resulted in similar cat expression in CHOdhfr- cells.

3T3 Cells↗
PubMed1996

Risk factors for hepatitis B virus infection among heterosexuals attending a sexually transmitted diseases clinic in Italy: role of genital ulcerative diseases.

The seroprevalence and risk factors for hepatitis B virus (HBV) infection were determined among 1,497 heterosexuals with no history of intravenous drug use (median age 32, range 15-78) treated at a sexually transmitted disease clinic in Rome. A total of 329 (22.0%) had antibodies to HBV core antigen (anti-HBc), a rate nearly four times as high as the 5.8% found recently in a national sample of young male adults, ages 18-26 years. Multiple logistic regression analysis showed that the risk of anti-HBc positivity was independently associated with male sex, increasing age, lower level of education, three or more sexual partners in the previous year, and positive syphilis serology. Lack of condom use, history of nonulcerative sexually transmitted diseases, and genital herpes were not associated with anti-HBc positivity. These findings confirm that heterosexual exposure plays an important role in the spread of HBV infection. Furthermore, these data indicate that individuals with more than two sexual partners a year and those with positive syphilis serology should be immunised against HBV.

Adolescent↗
PubMed1996

Involvement of glutamatergic and dopaminergic systems in the reactivity of mice to spatial and non-spatial change.

Injections of glutamatergic NMDA as well as dopaminergic antagonists produce selective place- but not cue-learning deficits in associative spatial tasks. The present work was aimed at examining if the blockade of NMDA and dopaminergic receptors interferes with the encoding of spatial information in a non-associative task specifically designed for rodents. CD1 mice injected with MK-801 (0.1 and 0.25 mg/kg), haloperidol (0.04 and 0.08 mg/kg), a combination of the lower doses of each drug (haloperidol: 0.04 mg/kg and MK-801: 0.1 mg/kg) or saline were placed in an open field containing five objects and their reactivity to the displacement (spatial change) or the substitution (non-spatial change) of some of these objects was examined. The results show that saline-injected mice reacted to spatial as to non-spatial change by increasing the time spent exploring the displaced objects or the substituted one. Both doses of MK-801 prevented mice from detecting spatial change but did not affect their reactivity to the novel object. Both doses of haloperidol abolished the reactivity of mice to spatial change but the higher dose of the drug also altered the reaction to non-spatial change. Taken together, the present results indicate that the blockade of dopaminergic or glutamatergic NMDA receptors abolishes the detection of spatial novelty. The well-documented impairing effects of haloperidol and MK-801 on spatial learning may, therefore, be the consequence of a drug-induced inability in forming and/or updating spatial representations. The effects of haloperidol was, however, less specific than that of MK-801, since haloperidol always modified activity together with the response to spatial change and, at the higher dose, abolished the detection of both spatial and non-spatial change. Finally, haloperidol pretreatment was found to enhance the effect of MK-801 thus suggesting a possible interaction between the two systems in modulating these behavioral responses.

Analysis of Variance↗
PubMed1996

Incidence of non-A, non-B and HCV positive hepatitis in healthcare workers in Italy.

In Italy, using figures from a surveillance system for acute viral hepatitis, the incidence rate of acute non-A, non-B hepatitis (NANBH) and hepatitis C virus (HCV) hepatitis cases was evaluated in healthcare workers (HCWs) and the general population of the same age over the period 1988-1994. The NANBH incidence among the general population declined from 4.7/100,000 in 1988 to 2.1/100,000 in 1994; the corresponding figures among HCWs were 12.3/100,000 (RR 2.62; CI 95% = 1.66-4.15) in 1988 and 4.3/100,000 (RR 2.05; CI 95% = 1.13-3.77) in 1994. Since 1991, NANBH cases have been tested for antibodies to HCV (anti-HCV). During the period 1991-1994 the proportion of NANBH cases tested for anti-HCV was 81% (38/47) in HCWs and 85% (1019/1193) in other NANBH cases. A similar proportion of NANBH cases in each group (74% and 70%) were shown to be due to HCV. The incidence rate of HCV positive cases among the general population was 1.3/100,000 in 1991 and 1.8/100,000 in 1994; the corresponding figures among HCWs were 3.7/100,000 (RR 2.85; CI 95% = 1.42-5.92) in 1991 and 3.1/100,000 (RR 1.72; CI 95% = 0.88-3.59) in 1994. The proportion of cases with jaundice was 56.2% in HCWs and 63.7% in the general population. Needlestick injury without major risk factors such as blood transfusion, intravenous drug use or surgical intervention was reported by 12.0% of HCWs and by 0.1% of the general population. Lack of any risk factor was reported by 40.2% of HCWs. These findings strongly suggest that in Italy healthcare workers are at greater risk than the general population of acquiring NANBH, as well as HCV.

Acute Disease↗
PubMed1996

Interobserver variability on the histopathologic diagnosis of cutaneous melanoma and other pigmented skin lesions.

PURPOSE: To assess the interobserver agreement on the diagnosis and classification of cutaneous melanoma. MATERIALS AND METHODS: A set of 140 slides of cutaneous melanoma, including a small subset of benign pigmented skin lesions, were circulated to four experienced histopathologists. The kappa statistic for multiple ratings per subject was calculated using the method described by Fleiss. RESULTS: The kappa value on the diagnosis of cutaneous melanoma versus benign lesions was 0.61. There was some discordance on the diagnosis in 37 of 140 cases (26%). For the histopathologic classification of cutaneous melanoma, the highest kappa values were attained for Breslow thickness (kappa = 0.76) and presence of ulceration (kappa = 0.87). The agreement was generally poor for other histologic features, such as level of dermal invasion (kappa = 0.38), presence of regression (kappa = 0.27), and lymphocytic infiltration (kappa = 0.27). CONCLUSION: Our study suggests considerable disagreement among pathologists on the diagnosis of melanoma versus other pigmented lesions. Tumor thickness and presence of ulceration are the most reproducible histologic features of cutaneous melanoma.

Humans↗
PubMed1996

Hepatitis B and C viruses, human T-cell lymphotropic virus types I and II, and leukemias: a case-control study. The Italian Leukemia Study Group.

The relationship between acute myeloid leukemia (AML), acute lymphocytic leukemia, chronic myeloid leukemia (CML), and refractory anemia with excess of blasts (RAEB) and antibodies to human T-cell lymphotropic virus types I and II (HTLV-I and HTLV-II), and hepatitis B virus and hepatitis C virus (HCV) was investigated in a multicenter case-control study. There were 431 cases enrolled in the study at the time of diagnosis of hematological malignancies, and 862 controls ages 15 years or older were recruited in three hospitals. Antibodies to HTLV-I and HTLV-II, antibody to HCV, hepatitis B surface antigen, and antibody to hepatitis B core antigen were assayed. All cases and controls were negative for HTLV-1 antibodies; one case (1 of 431; 0.2%), and one control (1 of 862; 0.1%) were found positive for HTLV-II antibodies. A nonsignificant excess of risk for hepatitis B surface antigen was present among RAEB cases (odds ratio, 2.40; 95% confidence interval, 0.46--12) CML, (odds ratio, 2.70; 95% CI, 0.86--8.43), and between antibody of hepatitis B core antigen and AML (odds ratio, 1.40; 95% CI, 0.93-2.10). A weak, nonsignificant association was present between AML, acute lymphocytic leukemia, RAEB, and antibody to HCV. These preliminary results suggest a possible association (elevated odds ratios) between hepatitis B virus, AML, RAEB, and CML. However, because all confidence intervals overlapped the null value, these findings need to be confirmed in larger case-control studies.

Acute Disease↗
PubMed1995

Interaction between the NMDA competitive antagonist CPP and the dopaminergic system in one-trial inhibitory avoidance in C57BL/6 mice.

Post-training administration of the N-methyl-D-aspartate (NMDA) receptors antagonist CPP, at doses of 0.5 and 1.0 mg/kg, impaired, in dose-dependent fashion, retention of the inhibitory avoidance response in C57BL/6J (C57) mice. Post-training subeffective doses of selective D1 and D2 dopamine receptor agonists, were able to antagonize the action of CPP, while subeffective doses of SCH 23390 and (-) sulpiride, respectively, D1- and D2-selective antagonists, enhanced the effects of the NMDA antagonist. Furthermore, subchronic blockade of dopamine receptor through a 10-day daily treatment with 4 mg/kg of haloperidol induced an adaptation of both the dopaminergic and the glutamatergic system. The possible upregulation of D2 receptors, in response to repeated injection with haloperidol is shown in the one-trial inhibitory avoidance by an increased response to the D2 agonist. In addition, our data show a potentiation of CPP effects after the same treatment. These results suggest a complex interaction between dopamine and glutamate in modulating one-trial inhibitory avoidance behavior in mice.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1995

Chronic treatment with MK-801 affects the behavioral response to both D1 and D2 dopamine agonist in the one-trial inhibitory avoidance.

Post-training administration of the N-methyl-D-aspartate (NMDA) antagonists CPP (0.5 and 1.0 mg/kg) and MK-801 (0.25 and 0.5 mg/kg) impaired, in a dose dependent fashion, the one-trial inhibitory avoidance response in NMRI mice. The D1 dopamine (DA) agonist SKF 38393 (10 and 20 mg/kg) and the D2 agonist quinpirole (0.5 and 1.0 mg/kg) instead facilitate the response in the same behavioral paradigm. Sub-chronic blockade of NMDA receptors with MK-801 (0.25 mg/kg once a day for 14 days) did not change the response to both competitive (CPP) and non-competitive (MK-801) NMDA antagonists. The same chronic treatment with MK-801 induced an increased response to both SKF 38393 and quinpirole. These data suggest that repeated administration of MK-801 induce an upregulation of both D1 and D2 DA receptors without affecting NMDA receptors.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1995

Effects of the NMDA-antagonist, MK-801, on stress-induced alterations of dopamine dependent behavior.

The effects of pretreatment with the non-competitive NMDA antagonist (+)MK-801 on the behavioral alterations induced by repeated restraint stress were investigated. Repeatedly stressed (restraint stress 2 h a day x 10 days) mice showed enhanced sensitivity to the inhibitory effects of a low dose of direct dopamine agonist, apomorphine (0.25 mg/kg), on climbing behavior. On the other hand, no changes were observed for the stimulatory effect of the high dose of apomorphine (3 mg/kg) on this behavioral response. Mice pretreated with MK-801 (0.15 mg/kg) before the stressful experience did not show altered response to the low dose of apomorphine (0.25 mg/kg). Finally, ten daily injections with 0.15 mg/kg MK-801 did not affect the behavioral response to the low dose of apomorphine, but enhanced the stimulatory effect of the high dose of the dopaminergic agonist on climbing behavior. Therefore, it is possible that the protective action of MK-801 against stress-induced behavioral alteration is due to changes in sensitivity of postsynaptic receptors.

Animals↗