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Biomedical subjects

A Mele

Publications and source records attributed to A Mele.

At least 91 records · Page 5Linked to original sources
PubMed1998

Stress promotes major changes in dopamine receptor densities within the mesoaccumbens and nigrostriatal systems.

This study investigated the effects of stress on brain dopamine receptor densities in two inbred strains of mice. Analysis of [3H]SCH23390 binding by quantitative autoradiography revealed that repeated restraint stress significantly increases D1-like receptor density in the nucleus accumbens of mice of the DBA/2 strain whist reducing it in the caudate-putamen of C57BL/6 mice. No significant changes in D2-like receptor quantified by [3H](-)-sulpiride binding were observed in caudate, substantia nigra and accumbens of stressed C57BL/6 mice. Instead, in DBA/2 mice, stress significantly increased D2-like receptor density in the nucleus accumbens whilst reducing it in the substantia nigra. Finally, stress significantly increased D2-like receptor density within the ventral tegmental area of C57BL/6 mice whilst significantly reducing it in mice of the DBA/2 strain. These results indicate that stress promotes major changes in mesoaccumbens and nigrostriatal dopamine receptor densities. The direction of these changes depends on receptor subtype, brain area and strain. Moreover, the opposite changes of D2-like receptor densities promoted by stress in the ventral tegmental area of the two inbred strains of mice suggest that mesoaccumbens dopamine autoreceptors density might be controlled by a major genotype x stress interaction.

Animals↗
PubMed1998

The relationships of chronic hepatitis and cirrhosis to alcohol intake, hepatitis B and C, and delta virus infection: a case-control study in Albania.

The present study examined the effect of hepatitis B virus (HBV) and alcohol intake, and the role of hepatitis delta virus (HDV) and hepatitis C virus (HCV) in the aetiology of chronic liver disease in Albania. A total of 106 cases of liver cirrhosis or chronic hepatitis were compared to 195 control patients without these or other liver diseases. Adjusted odds ratios were 52.7 (95% CI 22.7-122) for HBV surface antigen, 26.9 (95% CI 4.9-147) for anti-HCV, 26.2 (95% CI 3-1-221) for anti-HDV, 2.4 (95% CI 1.3-4.4) for lifetime alcohol intake and 2.3 (95% CI 1-5.5) for duration of alcohol intake. Although not significant, an interaction was suggested between HBsAg and anti-HCV and between HBsAg and alcohol intake. Our study underlines the role of hepatitis viruses in the development of chronic liver diseases. Additionally, it suggests that heavy alcohol intake may magnify the effect of HBV on these diseases. HBV vaccination and alcohol abstention appear to be important strategies to reduce the risk of liver cirrhosis and chronic hepatitis in Albania.

Adolescent↗
PubMed1998

Risk of human immunodeficiency virus infection and genital ulcer disease among persons attending a sexually transmitted disease clinic in Italy.

To assess the relative importance of ulcerative and non-ulcerative sexually transmitted disease in the transmission of HIV, a seroprevalence study was conducted on 2210 patients at the sexually transmitted diseases (STD) clinic of the S. Maria e S. Gallicano Hospital in Rome, between 1989 and 1994. Among male patients, by univariate analysis, strong predictors of HIV infection were homosexuality, sexual exposure to a HIV-positive partner, hepatitis B virus infection, and positive syphilis serology. An increased risk was estimated for patients with past genital herpes (odds ratio (OR) 3.86, 95% confidence intervals (CI) 0.40-18.2), and primary syphilis (OR 5.79, 95% CI 0.59-28.6). By multivariate analysis, a positive association was found with homosexuality (OR 6.9, 95% CI 2.9-16.5), and positive syphilis serology (OR 3.5, 95% CI 1.3-9.2). An adjusted OR of 2.41 was calculated for current and/or past genital herpes. These results, although not conclusive, suggest a role of ulcerative diseases as risk factors for prevalent HIV infection, and indicate that positive syphilis serology is an unbiased criterion for identifying individuals at increased risk of HIV infection.

Adult↗
PubMed1998

Secondary haematological neoplasm after treatment of adult acute lymphoblastic leukemia: analysis of 1170 adult ALL patients enrolled in the GIMEMA trials. Gruppo Italiano Malattie Ematologiche Maligne dell'Adulto.

Between 1983 and 1994 the incidence of secondary haematological neoplasms (SHM) was evaluated in 1170 new cases of ALL enrolled in the GIMEMA trials. Of the 942 patients who achieved complete remission (CR); seven developed a SHM: four AMLs and three NHLs. The median latency from onset of ALL and of secondary haematological neoplasm was 69 months for AML and 61 months for NHL. Three out of four patients with secondary AML were unresponsive to the new chemotherapy and died, whereas the fourth patient achieved a new CR. Among the three NHL cases, two patients are presently alive in CR, whereas the third patient was refractory to chemotherapy and died. The relative risk of haematological malignancy among the GIMEMA trials population, as compared to that of the Italian Cancer Registries, was 15.25-fold higher, and the actuarial estimated cumulative proportion of ALL patients with a secondary haematological neoplasm at 5 and 10 years were 0.59% and 3.63% respectively. The incidence of adult ALL who developed a SHM, although apparently lower than in the paediatric ALL series, was higher when compared to the normal population. The difference between paediatric and adult ALL is probably due to the lack of craniospinal radiotherapy and to the lower doses of epipodoxiphyllotoxins used in adult trials. The higher percentage of childhood ALL with a prolonged event-free survival could result in an increase of secondary neoplasms in these cases, which suggests that secondary haematological neoplasms in adult ALL patients are real, although rare, events.

Adolescent↗
PubMed1998

Hepatitis B vaccination coverage among healthcare workers in Italy.

In 1996, the vaccination coverage against hepatitis B virus among 3,157 healthcare workers in Italy was inversely related to the level of hepatitis B virus endemicity in the area of residence. Youngest age and lowest years of employment were independent predictors of the likelihood of vaccine acceptance.

Adult↗
PubMed1998

Structural characterization and independent folding of a chimeric glycoprotein comprising granulocyte-macrophage colony stimulating factor and erythropoietin sequences.

MEN 11300 is a hybrid glycoprotein of 297 amino acids obtained by fusion of the cDNA encoding GM-CSF with the cDNA encoding EPO followed by transfection of the hybrid gene into CHO cells. The oligonucleotide construct incorporated a spacing sequence between the two individual cDNAs which encodes eight amino acids constituting a linker peptide intended to separate the GM-CSF and EPO moieties. The recombinant MEN 11300 protein was submitted to a detailed structural characterization including the verification of the entire amino acid sequence, the assignment of the disulfide bridges pattern, the identification of the glycosylation sites and the definition of the glycosidic moiety, including site-specificity. Partial processing of the C-terminal Arg residue and the occurrence of N-glycosylation sites at Asn27, Asn155, Asn169, Asn214 were established. Moreover, O-glycosylation at Ser257 and at the N-terminal region was also detected. A large heterogeneity was observed in the N-glycans due to the presence of differently sialylated and fucosylated branched complex type oligosaccharides whereas O-linked glycans were constituted by GalGalNAc chains with a different number of sialic acids. The disulfide bridges pattern was established by direct FABMS analysis of the proteolytic digests or by ESMS analysis of HPLC purified fractions. Pairing of the eight cysteine residues resulted in Cys54-Cys96, Cys88-Cys121, Cys138-Cys292, and Cys160-Cys164. This S-S bridges pattern is identical to that occurring in the individual natural GM-CSF and EPO, thus showing that the two protein moieties in MEN 11300 can independently acquire their native three-dimensional structure.

Amino Acid Sequence↗
PubMed1998

Acute promyelocytic leukaemia: epidemiology and risk factors. A report of the GIMEMA Italian archive of adult acute leukaemia. GIMEMA Cooperative Group.

Acute promyelocytic leukaemia (APL) exhibits peculiar epidemiological, clinical, cytogenetic and molecular features, compared to the other acute myeloid leukaemias (AML). Data on epidemiology and occupational risk factors for APL desumed from the GIMEMA archive are reported and compared with those of the other AML. An exploratory case-case study was designed on AML patients from 56 haematology centres in Italy. Overall, 4296 patients older than 15 yr with a new diagnosis of acute leukaemia were recorded between July 1992 and July 1997. Of these, 335 were classified as APL, and 2894 as other AML. The median age of APL patients was 43 compared to 59 yr for the other AML (p < 0.00001). In order to identify peculiar risk factors for APL development, different parameters were compared in the 2 groups. After adjusting by age no significant differences were observed with regard to education, lifetime prevalence of cancer among siblings and previous diseases in the patient's history. Occupational exposure as a possible risk factor for APL showed no increased risk compared to other AML among farmers, builders and leather workers. A significant association was found in electricians (OR=4.4, 95% CI=2.0-9.7) and a weak association was found in wood workers (OR=3.2, 95% CI=0.8-10.8). The proportion of APL with respect to other AML was significantly higher in the north east of Italy compared to the rest of the country (OR=1.7, 95% CI=1.3-2.2). These data confirm the younger age of APL patients compared to the other AML. A possible role of electromagnetic fields is suggested by the higher risk of APL in electrical workers and in the more industrialized areas of the country.

Adolescent↗
PubMed1997

Alterations in striatal dopamine overflow during rotational behavior induced by amphetamine, phencyclidine, and MK-801.

Rats lesioned unilaterally in the medial forebrain bundle with 6-OHDA rotated ipsilateral to the lesion following injections of amphetamine, phencyclidine (PCP), and MK-801. Concurrent measurement of striatal dopamine (DA) in the intact striatum with in vivo microdialysis revealed a dissociation between rotational behavior and alterations in DA overflow induced by the three drugs. Amphetamine produced robust ipsilateral rotational behavior and a substantial elevation in striatal DA (approximately 130% increase at asymptote). PCP produced comparable increases in rotational behavior, but only approximately 30% increase in striatal DA. MK-801 also had a comparable behavioral effect but failed to alter DA overflow in the intact striatum. Since MK-801, a noncompetitive NMDA antagonist which does not enhance extracellular dopamine in the striatum, is able to produce ipsilateral rotational behavior in rats with unilateral nigrostriatal lesions, it is likely that the effects of PCP may also be determined predominantly through NMDA blockade in this model.

Amphetamine↗
PubMed1997

High-level expression of a cDNA for human granulocyte colony-stimulating factor in Chinese hamster ovary cells. Effect of 3'-noncoding sequences.

We compared the production of recombinant human granulocyte colony-stimulating factor (rhG-CSF) by Chinese hamster ovary (CHO) cells in a transient expression system, using different analogous vectors carrying a human G-CSF-encoding cDNA under the transcriptional control of the murine cytomegalovirus (CMV) major immediate early promoter. Comparison of two transcription units carrying a human (h)G-CSF cDNA deleted of 3'-untranslated (UTR) sequences containing AT-rich elements (ARE) and using 3'-UTR sequences for processing of transcripts from the SV40 early region or from the rabbit beta 1-globin gene showed that use of the sequences from the rabbit beta 1-globin gene resulted in 7- to 12-fold higher levels of rhG-CSF production. Deletion of ARE of hG-CSF cDNA resulted in increased rhG-CSF synthesis when transcription units using 3'-UTR sequences from the rabbit beta 1-globin gene were compared. By contrast, deletion of ARE did not appear to affect rhG-CSF production when 3'-UTR sequences from the SV40 early region were used. The most efficient G-CSF transcription unit, fused to a dihydrofolate reductase (DHFR) marker gene and transfected into a CHO cell line, yielded initial transfectant CHO cell lines secreting up to 21 micrograms rhG-CSF/1 x 10(6) cells in 24 h. After two rounds of DHFR gene amplification, a cell line was isolated that contains approx 12 copies of the vector and produces rhG-CSF at a rate of 90 micrograms/1 x 10(6) cells in 24 h.

Animals↗
PubMed1997

Incidence of and risk factors for hepatitis A in Italy: public health indications from a 10-year surveillance. SEIEVA Collaborating Group.

BACKGROUND/AIMS: This study aimed to evaluate the incidence of and risk factors for acute viral hepatitis A (HAV) in Italy. METHODS: Data were from a surveillance system for type-specific acute viral hepatitis (SEIEVA). To estimate the association of hepatitis A cases with the potential risk factors (Odds Ratios) and the proportion of all hepatitis A cases attributable to a given risk factor (population attributable risk), hepatitis B cases were used as controls. Independent predictors of HAV were estimated by conditional multiple logistic regression. RESULTS: During the period 1985-1994, 25553 viral hepatitis cases were reported. Of these, 6408 (25%) were due to hepatitis A (HAV). HAV incidence declined from 10/100000 in 1985 to 2/100000 in 1987. Since 1991, however, an increase in HAV has been observed. The majority of cases were 15-24 years old; the incidence was higher in males and in subjects residing in southern Italy. Only one death (0.02%) was observed. Shellfish consumption was the most frequently reported risk factor (62%). The proportion of cases reporting personal contact with an icteric case, travel to a high-medium endemic areas, and family contact with a child attending a day-care centre (household of day-care child) was 17%, 19% and 15%, respectively. The results of multivariate analysis showed that shellfish consumption (OR=2.6; 95% CI=2.4-2.9), travel to endemic areas for people residing in northern and central Italy (OR=5.4; 95% CI=4.6-6.2) and household of day-care child (OR=1.2; 95% CI=1.03-1.4), were all types of exposure independently associated with HAV. The estimates of population-attributable risk show that shellfish consumption explained as many as 42.2%, travel to high-medium endemic areas for people residing in northern and central Italy 24.2%, and household of day-care child only 1.4% of all acute hepatitis A cases in Italy. CONCLUSIONS: These findings indicate that HAV in Italy is mainly a food-borne disease. Vaccination against hepatitis A is strongly recommended for travellers to endemic areas.

Adolescent↗
PubMed1997

Vaccination campaign against hepatitis B for 12-year-old subjects in Italy.

The vaccination campaign against hepatitis B for 12-year-old subjects in Italy was evaluated in 136 health districts (USL); 55 in the north, 69 in the centre, and 12 in the south, respectively. Out of the 113,230 eligible subjects born in 1981, 105, 989, (93.6%) completed the three dose series during the period 1993-1994. However, wide geographical differences are observed: the acceptance rate was as high as 97.9% (range 89.7-100.0) and 96.6% (range 76.0-100.0) in the north and in the centre, respectively; but only 65.1% in the south (range 26.8-100.0). Subjects were recruited in the north and in the centre mostly from the list of residents, while in the south more likely only from the list of people attending school. The school attendance in the south, not as good as in the other Italian areas, particularly among people belonging to a subgroup of the population economically disadvantaged, appears to be a strong determinant of the different vaccine coverage observed. Active efforts from health services in southern areas are necessary to reach subgroups of population who escape hepatitis B vaccination and who are also at high risk of HBV infection.

Child↗
PubMed1997

Ibotenic lesions of the nucleus accumbens promote reactivity to spatial novelty in nonreactive DBA mice: implications for neural mechanisms subserving spatial information encoding.

The role of the nucleus accumbens (NA) in forming spatial representations was investigated in C57BL/6 (C57) and DBA/2 (DBA) inbred mice. One week before testing, bilateral excitotoxic lesions were performed in the NA using ibotenic acid. Testing consisted of placing mice in an arena containing 5 objects at a fixed location and, after habituation to the object configuration, examining their reactivity to the displacement (spatial novelty) or the substitution (object novelty) of some of these objects. C57 mice reacted to spatial novelty and DBA mice did not. Both strains, however, reacted to object novelty. The lesion had no effect on C57 mice's performance, but in the DBA mice, it promoted a clear reaction to spatial novelty that was absent in control animals. Radial maze performance also was improved in DBA with NA lesions. Results suggest the NA as a possible site for modulating spatially mediated behaviors in poor-performing subjects.

Animals↗
PubMed1997

Immunoconjugates made of an anti-EGF receptor monoclonal antibody and type 1 ribosome-inactivating proteins from Saponaria ocymoides or Vaccaria pyramidata.

The present paper describes two immunoconjugates consisting of an anti-epidermal growth factor receptor (EGFR) monoclonal antibody (MAb), named Mint5, covalently linked to the type 1 ribosome-inactivating proteins (RIPs) ocymoidine (Ocy) and pyramidatine (Pyra) from Saponaria ocymoides and Vaccaria pyramidata respectively. Both antibody and toxins are shown to retain their respective biological properties upon chemical conjugation. The immunoconjugates exert specific inhibition of EGFR expressing target cell proliferation and protein synthesis in in vitro assays and also inhibit the growth of grafted human tumour cells in nude mice.

Animals↗
PubMed1997

Risk factors for acute hepatitis B: a case-control study.

Over the period 1989-1991 a case-control study was carried out in the area of Naples comparing 162 subjects with acute hepatitis B and 788 hospitalized control subjects. The results of multivariate analysis showed that surgical intervention (odds ratio 3.8; 95% CI 1.2-11.7), household contact with an hepatitis B surface antigen (HBsAg) positive carrier (odds ratio 2.7; 95% CI 1.1-6.7) and intravenous drug use (odds ratio 13.0; 95% CI 3.2-52.7) were risk factors independently associated with hepatitis B. No association was found with the other risk factors considered, such as blood transfusion, hospitalization, other percutaneous exposures, dental therapy, contact with an icteric case, barber shop shaving and two or more sexual partners. As a significant proportion of the general population undergoes surgical intervention, efficient procedures for sterilization of instruments should be implemented, together with the use of disposable materials, to control the spread of HBV infection in surgical settings.

Acute Disease↗
PubMed1997

Production of recombinant human GM-CSF-EPO hybrid proteins: in vitro biological characterization.

Selective lineage differentiation depends upon the combined action of several colony-stimulating factors. Here we describe 3 human granulocyte-macrophage colony-stimulating factor-erythropoietin (GM-CSF-EPO) hybrid proteins generated by recombination of the relevant cDNAs. The expression vector containing the murine cytomegalovirus (mCMV) promoter and dihydrofolate reductase (DHFR) gene was used for the expression of the hybrid genes in Chinese hamster ovary (CHO) cells. Purified hybrid proteins from CHO transfectant cultures induced proliferation of both EPO and GM-CSF dependent cell lines. The clonogenic test, performed on purified human hematopoietic precursor cells, indicates that the hybrid proteins are more efficient at inducing erythroid differentiation compared with the equimolar mixture of GM-CSF and EPO.

Amino Acid Sequence↗
PubMed1997

Case fatality rate of acute hepatitis in Italy: results from a 10 year surveillance.

Using data from the surveillance system for acute viral hepatitis we have evaluated the case fatality rate of viral hepatitis in Italy. 71 deaths (0.3%) occurred among the 21,553 reported acute viral hepatitis cases from 1985-1994. None reported history of exposure to drugs or toxins. The highest case fatality rate was observed for B and NANB hepatitis (0.5%). One death occurred among the 6,353 (0.02%) hepatitis A cases and 1 among the 909 (0.1%) anti-HCV positive NANB hepatitis cases. The case fatality for Delta hepatitis was 0.2% (1/422). Case fatality rate was similar in both sexes; increasing with age; 0.03% were < 15 years of age, 0.1%, 15-24 year-old, and 0.5%, > or = 25 years. Subjects older than 24 years of age accounted for 81.4% of total deaths. Intravenous drug use, blood transfusion and other parenteral exposures were the three most frequent non-mutually exclusive sources of infection reported by subjects who died from B and NANB hepatitis. These findings indicate that the survival rate of acute B and NANB hepatitis is lower than that of acute hepatitis A; moreover in Italy, as in other Western countries, acute HCV seems to cause liver failure only rarely.

Adolescent↗
PubMed1997

Risk factors for hepatitis B virus infection among homosexual men attending a sexually transmitted diseases clinic in Italy.

Prevalence of and risk factors for hepatitis B virus (HBV) infection were determined among 252 homosexual men with no history of intravenous drug use (median age 33 years, range 18-77) treated at a sexually transmitted disease (STD) clinic in Rome. The overall prevalence of antibodies to HBV core antigen (anti-HBc) was 50.8%, a rate nearly nine times as high as the 5.8% found recently in a national sample of young male adults, aged 18-26 years, and twice as high as the 22% found in heterosexuals attending the same clinic over the same period of time. Multiple logistic regression analysis showed that the risk of anti-HBc positivity was independently associated with increasing age, five or more sexual partners in the previous year, positive HIV serology and positive syphilis serology. Lower level of schooling, lack of condom use, history of non-ulcerative STD, current or past history of genital herpes, and positive anti-HCV serology were not associated with anti-HBc positivity. These findings corroborate the importance of sexual transmission of HBV in homosexual men. Behavioural factors, such as multiple sexual partners, probably enhance the efficiency of this mode of HBV transmission.

Adolescent↗