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Biomedical subjects

L Conti

Publications and source records attributed to L Conti.

At least 91 records · Page 5Linked to original sources

Selective alteration of the turnover of interferon beta mRNA in peritoneal macrophages from LPS-hyporesponsive mice and its role in the defective expression of spontaneous interferon.

Basal levels of interferon (IFN)-beta mRNA transcription were detected in both freshly explanted LPS-responsive (Lpsn) and LPS-hyporesponsive (Lpsd) peritoneal macrophages (PM). In vitro cultivation of PM resulted in a time-dependent reduction in the level of IFN-beta mRNA, which was far more rapid in Lpsd than in Lpsn PM. Treatment of Lpsn PM with cycloheximide (CHX) resulted in a marked accumulation of IFN-beta mRNA, which was not associated with an increase in IFN-beta gene transcription. However, treatment of Lpsd PM with CHX did not induce accumulation of IFN-beta mRNA. CHX induced the accumulation of IFN-alpha-4 mRNA in both Lpsn and Lpsd PM, CHX enhanced the accumulation of two cytoplasmic factors interacting with AU-rich sequences within the 3' untranslated region of IFN-beta mRNA. We conclude that Lpsd PM exhibit an impaired capacity to stabilize IFN-beta mRNA that may account for their low expression of IFN-beta.

Animals↗

Abnormal thyroid function test results in patients with Fisher-Evans syndrome.

Thyroid function was evaluated in patients affected by Fisher-Evans syndrome (FES) and compared to that of patients affected only by autoimmune hemolytic anemia (AIHA) and to that of patients affected only by idiopathic thrombocytopenic purpura (ITP). The study population consisted of 20 patients with FES, 44 with AIHA and 20 with ITP. All patients were examined for thyroid function abnormalities and thyroid autoantibodies. Abnormal thyroid function test results were observed in 40, 25 and 10% of the patients, respectively. The prevalence of antithyroid antibodies (ATA) in FES was 25%; this is higher than the sum of the prevalences of ATA in patients affected only by AIHA (11.4%) or only by ITP (none). Subclinical primary hypothyroidism and hyperthyroxinemia with or without hypertriiodothyroninemia, with TSH serum levels below normal, were present in 20% and 10% of patients affected by FES, respectively. Of the former, 75% were positive for ATA. These results: i) confirm the high prevalence of abnormal thyroid test results in patients affected by AIHA, ITP and FES; ii) demonstrate the higher prevalence of autoimmune hypothyroidism in FES; iii) lead to the possibility of including FES as one of the multiple autoimmune syndromes.

Adolescent↗

Quantitative structure-activity relationship models correctly predict the toxic and aneuploidizing properties of six halogenated methanes in Aspergillus nidulans.

In a previous study, the relationships between the chemical structure and the ability of 35 chlorinated aliphatic hydrocarbons to induce aneuploidy and toxicity in Aspergillus nidulans were analyzed. Quantitative structure-activity relationships (QSAR) were defined for each of the biological activities under study: ARR (the dose able to block mitotic growth), D37 (the dose with 37% of survival) and LEC (the lowest efficient concentration in aneuploidy induction). In this study, these QSAR equations were used to predict the toxic and genetic activity of a further six chemicals, not included in the previous data base: bromotrichloromethane, bromoform, bromochloromethane, bromodichloromethane, dibromochloromethane and dibromochlorofluoromethane. Their ARR, D37 and LEC values were measured, and were in agreement with the predicted values, with correlation coefficients around 0.99. Furthermore, the QSAR model, which had previously been developed to discriminate between aneugenic and inactive halogenated hydrocarbons, correctly predicted the aneugenic activity of five out of six methanes. These correct predictions confirmed the validity of our QSAR model, according to which the induction of aneuploidy in A. nidulans depends on both the electrophilic and steric properties of the chemicals, whereas toxicity mainly depends on steric factors.

Aneuploidy↗

Sociodemographics and HIV risk behaviors of bisexual men with AIDS: results from a multistate interview project.

OBJECTIVE: To describe the sociodemographic characteristics and sexual and drug use behaviors of men with AIDS who engage in bisexual activity. METHODS: We interviewed 2120 men aged > or = 18 years who were reported with AIDS in 11 states and cities. Men were considered bisexual if they reported having had sex with a man and a woman in the previous 5 years. RESULTS: Of the 2020 men with AIDS who reported being sexually active in the previous 5 years, 1150 (57%) had had male partners only, 522 (26%) had had female partners only and 348 (17%) had had both. White men were least likely to report bisexual behavior (15%; 161 out of 1071). Men of Latin American descent were most likely to report bisexual behavior (24%; 37 out of 155), especially those born outside the United States who had lived there for < or = 10 years (38%; 11 out of 29). Bisexual Latin American men, regardless of birthplace, were more likely to be currently married than all other bisexual men (22 versus 7%; P < 0.05). HIV risk behaviors differed between men reporting bisexual and those reporting exclusively homosexual or heterosexual activity. Injecting drug use in the previous 5 years was more common among bisexual than homosexual men (12 versus 6%; P < 0.05). Bisexual men were more likely (P < 0.05) to have received money for sex (11%) than homosexual (4%) or heterosexual men (4%). This difference was even greater among injecting drug users receiving money for sex: bisexual (29%), homosexual (13%), heterosexual (3%). CONCLUSIONS: Demographics and HIV risk behaviors of bisexual men with AIDS differ from those of homosexual and heterosexual men with AIDS. These findings indicate that special efforts are needed to prevent sexual transmission of HIV among bisexual men.

Acquired Immunodeficiency Syndrome↗

Causes of death among persons reported with AIDS.

OBJECTIVES: This study describes causes of death in persons with acquired immunodeficiency syndrome (AIDS) and assesses the completeness of reporting of human immunodeficiency virus (HIV) infection or AIDS on death certificates of persons with AIDS. METHODS: AIDS case reports were linked with death certificates in 11 local/state health departments; underlying and associated causes of death were available for 32,513 persons with AIDS who died. RESULTS: HIV/AIDS was designated as the underlying cause of death for 46% of persons with AIDS who died between 1983 and 1986 and 81% of persons with AIDS who died since 1987 (the year specific coding procedures were implemented for HIV/AIDS). Most other underlying causes of death were conditions within the AIDS case definition (notably Pneumocystis carinii pneumonia), pneumonia, infections outside the AIDS case definition, and drug abuse. Unintentional injuries, suicide, and homicide were less common. HIV/AIDS was listed as underlying or associated on 88% of death certificates from 1987 to 1989; reporting varied primarily by HIV exposure category and time between diagnosis and death. CONCLUSIONS: Physicians and other health care professionals should realize their critical role in accurately documenting HIV-related mortality on death certificates. Such data can ultimately influence the allocation of health care resources for HIV-infected individuals.

Acquired Immunodeficiency Syndrome↗

AIDS epidemic among Florida women.

Impact of the human immunodeficiency virus among women in Florida is increasingly recognized in the second decade of the AIDS epidemic. Illicit drug use, sexual activity with multiple partners, lack of access to health care, and socioeconomic disadvantages are greatly contributing to the increase of female AIDS cases. Current salient features of the epidemic are summarized as well as prevention strategies to reduce transmission of the virus.

AIDS-Related Opportunistic Infections↗

Further in vitro and in vivo mutagenicity assays with thiram and ziram fungicides: bacterial reversion assays and mouse micronucleus test.

The fungicides thiram and ziram have been assayed in a battery of nine bacterial strains of different genetic specificity. The results obtained suggest the induction of excisable DNA lesion(s), and indicate similar mutability of strains with AT or GC base pairs at target sites. This mutagenic profile is clearly distinct from that of oxidative mutagens, and it does not support the proposed role of oxidative stress in the mechanism of dithiocarbamates mutagenicity in bacteria. Furthermore, the bone marrow micronucleus test has been carried out in B6C3F1 mice with intraperitoneal administration of high grade thiram (12.5-50 mg/kg) and ziram samples (2.5-10 mg/kg in males, and 5-20 mg/kg in females). Thiram produced a significant increase of micronucleated PCEs in male mice sampled 48 h after treatment with 25, 37.5, and 50 mg/kg. No significant increase was detected in treated females. Ziram, tested in a lower range of doses because of its higher toxicity, resulted negative in both sexes. Both the acute toxicity and the ratio polychromatic/normochromatic erythrocytes indicated some sex specificity in the toxic effects induced by these dithiocarbamates in the B6C3F1 mouse.

Animals↗

The induction of mitotic chromosome malsegregation in Aspergillus nidulans. Quantitative structure activity relationship (OSAR) analysis with chlorinated aliphatic hydrocarbons.

The biological activity of 24 chlorinated aliphatic hydrocarbons has been studied in the mold Aspergillus nidulans. The ability to induce chromosome malsegregation, lethality and mitotic growth arrest has been experimentally determined for each chemical. These data, together with those of 11 related compounds previously investigated, generated a data base which was used for quantitative structure-activity relationship (QSAR) analysis. To this aim, both physico-chemical descriptors and electronic parameters of each compound have been calculated and included in the analysis. The QSAR analysis indicated that toxic effects induced by chlorinated aliphatics in A. nidulans are mainly dependent on steric factors, as indicated by the correlation with molar refractivity (MR). Conversely, the ease with which they accept electrons, parametrized by LUMO (energy of the lowest unoccupied molecular orbital), plays a prevailing role in determining the aneuploidizing properties. An involvement of free radicals, generated by the reductive metabolism of haloalkanes, is hypothesized as an explanation of the data.

Aneuploidy↗

Cyclic AMP-mediated inhibition of vesicular stomatitis virus and herpes simplex virus replication in mouse macrophage-like cells.

In this study, we have analysed the effects of cAMP inducers on the multiplication of vesicular stomatitis virus (VSV) and herpes simplex virus type 1 (HSV-1) in mouse macrophage-like cells. The addition of dibutyryl cAMP (dB-cAMP) or cholera toxin to resting peritoneal macrophages aged in vitro or P388D1 cells resulted in a 10- to 100-fold reduction of VSV yield compared to control cultures. In contrast, no cAMP-dependent inhibition was found in VSV-infected L929 cells. In macrophage-like cells, the dB-cAMP-induced antiviral state was not inhibited by antibodies to interferon (IFN)-alpha/beta and did not correlate with any increase in the intracellular levels of 2-5 oligo(A) synthetase. Dibutyryl cAMP did not inhibit virus yields in mouse macrophages infected with encephalomyocarditis virus. In P388D1 cells, the addition of dB-cAMP resulted in an approximately 10-fold inhibition of HSV-1 replication with respect to control cultures, as evaluated both by TCID50 and plaque assays on Vero cells. Dibutyryl cAMP did not affect VSV binding or entry into mouse macrophages and the cAMP-mediated anti-VSV state was significantly reduced by inhibitors of protein kinase C (i.e. staurosporine and H7). These data suggest that macrophages may acquire resistance to infection by VSV and HSV-1 after treatment with cAMP inducers. This cAMP-mediated antiviral activity does not depend on the modulation of the endogenous IFN system, suggesting that macrophages exhibit multiple resistance mechanisms (i.e. IFN-dependent and IFN-independent) to maintain their intrinsic antiviral activity.

2',5'-Oligoadenylate Synthetase↗

Hemolytic anemia and thrombocytopenia induced by cyanidanol.

Five patients who received cyanidanol for 4-36 months are presented. Three developed both hemolytic anemia and thrombocytopenia, while 2 had only thrombocytopenia. After suspending the drug the hematological values returned to normal in all of the patients. Drug-dependent platelet antibodies were detected in 4 of the 5 patients and cyanidanol-dependent red blood cell antibodies were present in 3. There are various mechanisms involved in the cyanidanol-induced immune cytopenias and, as in the present study, were sometimes simultaneously observed in the same patient.

Aged↗

Prognostic value of autoantibodies against erythrocytes and platelets in chronic lymphocytic leukemia (CLL).

Antiglobulin test (AT) and Dixon tests were performed in 100 patients with CLL. Thirty-five of them had Rai stages 0 or 1, 19 stage 2, 13 stage 3, and 33 stage 4. Twelve patients showed red blood cells autoantibodies (RBCAb) positivity; positivity at Dixon test (direct, indirect, or both) was observed in 74%. The presence of autoantibodies against erythrocytes and platelets did not influence survival curves, but anemia and thrombocytopenia are considered risk factors, independently of the presence of an autoimmune disorder. Nine RBCAb positive patients with positive Dixon test had the worst survival curves, 5 of these were anemic and 1 thrombocytopenic and anemic.

Aged↗

Platelet imipramine binding in intensive care unit suicidal patients.

3H-Imipramine binding in relation to serotonergic function was studied in patients hospitalized following a suicide attempt. Comparison with a control group showed a highly significant difference in Bmax values. The results suggest, at least a posteriori, a biological alteration as the basis of suicidal behaviour. Although it is impossible to attribute a suicidal attempt to the alteration or to a predisposing pre-existent condition, this biological marker may be useful in evaluating suicidal risk and also short- and long-term prognosis.

Adult↗

Mutagenicity spectra in bacterial strains of airborne and engine exhaust particulate extracts.

The mutagenicity spectra of the organic extracts of both airborne particulate matter and diesel and gasoline soot particles were determined using a battery of 9 bacterial strains of different genetic specificity. The assays with crude extracts and with fractionated acidic, neutral and basic components revealed striking differences in the patterns of mutagenic responses produced by each of the complex mixtures investigated. The mutagenicity of air particulate matter was shown to depend mainly on direct-acting acidic and neutral compounds, with a lesser contribution of basic promutagens which required exogenous metabolic activation by liver S9. The assays with a diesel soot extract indicated the prevailing contribution of direct-acting acidic and neutral compounds, and suggested an important role also for nitro derivatives other than nitropyrenes. The gasoline exhaust was characterized by powerful promutagenic compounds, belonging to either the acidic, neutral or basic fractions. The implications of these results are discussed with respect to the contribution of engine exhausts to air pollution, and the possible use of mutagenicity spectra in the analysis of environmental complex mixtures.

Air Pollutants↗

Further studies on the comutagenic activity of cigarette smoke condensate.

The comutagenic effect exerted by cigarette smoke condensate (CSC) was investigated. In vitro experiments with Salmonella typhimurium strains TA98 and TA98/1.8DNP6 indicated that CSC specifically enhances the mutagenicity of polyaromatic amines such as 2-aminofluorene, 2-acetylaminofluorene, 4-acetylaminofluorene and 2-aminoanthracene. The pattern of comutagenicity of CSC was shown to differ from that of norharman, a tobacco-related known comutagenic substance. Both black and blond tobacco CSCs proved to interact synergistically with 2-aminoanthracene mutagenicity. Chemical fractionation of CSC indicates the occurrence of comutagenic substance(s) in both neutral and basic components. Further in vitro experiments with 2-acetylaminofluorene metabolites and derivatives suggest that the comutagenic effect of CSC could involve later step(s) in the metabolic activation of fluorenylamines, i.e., the conversion of hydroxylamines into ultimate reactive species. The possible occurrence of a synergistic interaction of CSC with chemical mutagens in vivo was evaluated. Administration of 2-aminoanthracene/CSC mixtures, previously shown to be comutagenic in vitro, failed to demonstrate a synergistic effect in SCE induction in bone marrow cells of mice. This apparent discrepancy may rely on divergences in the activation pathways of polycyclic amines in vitro and in vivo.

2-Acetylaminofluorene↗

Glycosaminoglycan polysulfate in the treatment of old age dementias.

1. In a multicenter, placebo-controlled, double-blind clinical trial in 155 elderly patients with cognitive decline, glycosaminoglycan polysulfate was found to be a therapeutically effective agent in the treatment of old age dementias. 2. Treatment with glycosaminoglycan polysulfate in the daily dosage of 600 LRU, administered on the basis of a divided dosage schedule for 12 weeks, was significantly superior to an inactive placebo on several outcome measures including the Wechsler Memory Scale-Russell Revision (Easy Paired Associates Learning and Immediate Visual Reproduction), Mini Mental State Examination, the Sandoz Clinical Assessment Geriatric (Cognitive Dysfunction and Depression), Hachinski Dementia Scale, Brief Psychiatric Rating Scale (Confusion and Depressive Withdrawal) and Global Improvement Scale of the Clinical Global Impression. 3. Adverse effects with glycosaminoglycan polysulfate were few and mild. The drug was equally well tolerated and equally effective in the two major dementias of old age, i.e., primary degenerative and multi-infarct. The number of abnormal laboratory test readings remained essentially unchanged from pre-treatment to post-treatment.

Activities of Daily Living↗

Aggression and suicide attempts: preliminary data.

The similarities between blood platelets and serotonin (5HT) neurons offer a reliable tool of exploring 5HT system. The aim of our study was to evaluate platelet [3H]imipramine binding in suicide attempters, as compared with depressed patients and healthy controls. In addition, we measured aggressive features in the 3 groups, by a standardized rating scale, the Inventory for assessing different kinds of ostility (QTA). The results showed a significant decrease in the maximum binding capacity (Bmax) of 3H-imipramine binding to platelet membranes in suicide attempters, who also exhibited higher total and single item scores at QTA than healthy controls or depressed patients. Both biological and psychological findings are suggestive of an aggression dysregulation in suicide attempters.

Adult↗

In vitro studies with nine known or suspected spindle poisons: results in tests for chromosome malsegregation in Aspergillus nidulans.

Within the framework of a coordinated collaborative study for evaluating assays for aneuploidy, nine known or suspected spindle poisons were tested in mitotic segregation assays with Aspergillus nidulans. Experiments with A. nidulans diploid strain P1 revealed a statistically significant increase of whole chromosome segregants (non-disjunctional diploids and haploids) after treatments with chloral hydrate (CH), thiabendazole (TB), thimerosal (TM) econazole (EZ) and hydroquinone (HQ). The latter two chemicals also increased the frequency of mitotic cross-overs. Colchicine (COL), diazepam (DZ), cadmium chloride (CD) and pyrimethamine (PY) were ineffective. Further experiments with CH, TB, TM and EZ in the haploid strain 35 demonstrated that CH, TB and TM induced hyperploid types, thus indicating a primary effect on chromosome segregation in A. nidulans. However, since EZ did not induce putative hyperploids in strain 35 and trisomics in diploid 31, it is suggested that EZ affects chromosome segregation by an indirect mechanism, possibly related to induced structural chromosome damage, as previously shown for HQ.

Aneuploidy↗