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Biomedical subjects

M Clerici

Publications and source records attributed to M Clerici.

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

Cytokines production in chronic schizophrenia patients with or without paranoid behaviour.

1. Several immunological abnormalities have been found in schizophrenia but their significance still remains largely unknown. In this study the authors analyzed mitogen-stimulated interleukin (IL)-2, Interferon gamma (IFN)-gamma and IL-10 (type 2 cytokine) production in a sample of 37 chronic schizophrenic patients as compared with a sample of 40 age and sex-matched controls with the aim to evaluate whether patients belonging to different diagnostic subtypes (i.e. paranoid patients vs non paranoid patients) could be immunologically different from each other. 2. The findings indicate that paranoid patients produce less IL-10 than the others and thus, from an immunological viewpoint, they are more similar to healthy controls. 3. Furthermore, neuroleptic medications were observed to differently affect IL-2 production; this preliminary finding might stimulate further studies aiming to get a link between different drug profile of action both in terms of clinical and receptorial profile and different immunological effects.

Adult↗
PubMed1998

Low CD4 counts rather than superantigenic-like effects account for differences in expressed T-cell receptor (TCR) repertoires between HIV-1 seropositive long-term non-progressors and individuals with progressive disease.

Analysis of HIV-infected individuals who have stable CD4 counts many years after seroconversion may provide an insight as to how the host's immune system can successfully control HIV infection. In this study we analysed the T-cell receptor (TCR) Vbeta repertoire in 13 HIV+ individuals, seven of whom were classed as long-term non-progressors (LTNP), using a technique which couples anchor PCR (AnPCR) amplification of beta-chain cDNA to differential probe hybridization with non-radioactively labelled Vbeta family specific oligonucleotide probes. There were no significant differences in the expressed TCR repertoires between the LTNP group and the other HIV-infected individuals. However, there was a statistically significant inverse correlation between CD4 count and the number of Vbeta family-specific perturbations in the recent seroconverters (SC) and those with progressive infection (PI), consistent with other shared features of clinical disease progression (Th1/Th2 switch and high frequency of viral isolation). We conclude that long-term clinical non-progression in HIV-1 infection is not associated with the loss or expansion of a particular Vbeta family; instead, low CD4 count in the PI and SC individuals was correlated with increased number of Vbeta family-specific perturbations relative to the LTNP group and that it is hence unlikely that HIV encodes a superantigen.

Adult↗
PubMed1998

Family adaptation to institutionalised mentally retarded patients. A preliminary report on an Italian population.

Family interactive patterns were investigated in the relatives of 20 mentally retarded patients institutionalised in two centres in Northern Italy. Expressed emotion (EE) was used as evaluation instrument. The results show a surprisingly high rate (45%) of high EE, even in relatives of patients who did not live inside the family. High EE was positively correlated to the presence of behavioral disorders in the patients, as already shown for children with conduct disorders. Treatment implications are discussed; there is an opportunity for the implementation of a family psychoeducational approach, aimed both at managing the behavioural consequences of the disorder and at enhancing rehabilitation programmes.

Adaptation, Psychological↗
PubMed1998

International collaborative study for the calibration of a proposed reference preparation for thromboplastin, human recombinant, plain. On behalf of the Subcommittee on Control of Anticoagulation.

Stocks of the International Reference Preparation (IRP) for thromboplastin, human, plain, coded BCT/253 and held by the World Health Organization (WHO) are nearly exhausted and must be replaced. For practical reasons the choice of the replacement candidate was restricted to two available human recombinant preparations which were coded as X/95 and Y/95 and calibrated in an international collaborative study involving 19 laboratories from Europe, Australia, Canada and Argentina. To minimize the differences between routes of calibration, the two candidates were calibrated against the existing WHO-IRP from human, rabbit and bovine origin and the final ISI was the resultant average value. On the basis of predefined criteria (i.e., within- and between-laboratory precision of the calibration and the conformity to the calibration model), X/95 was the preferred candidate. The assigned ISI (SE of the mean) value is 0.940 (0.0060) and the interlaboratory coefficient of variation 4.7%.

Animals↗
PubMed1998

Assessment of the influence of citrate concentration on the International Normalized Ratio (INR) determined with twelve reagent-instrument combinations.

Citrate concentration is one of the variables that can affect coagulation tests. However, few studies have so far been performed to assess the magnitude of this effect on coagulation tests in general and PT in particular. The aim of this study was to assess the extent of influence of citrate concentration on the PT test with results expressed as INR. Twelve reagent-instrument combinations (systems) were calibrated vs. the Reference Preparation BCT/441 using plasmas collected in either 105 mM or 129 mM citrate from normals and anticoagulated patients (OAT). PTs for plasmas collected in 129 mM citrate were longer than those collected in 105 mM both for normals and patients on OAT, but the ratios (patient-to-normal clotting times) for the two citrate concentrations were significantly different in many instances, implying that the International Sensitivity Index (ISI) is also different. ISIs for calibrations with plasmas collected in 105 mM were greater (up to 10%) than those with plasmas collected in 129 mM citrate. When PT ratios were transformed into INR using crossover ISIs (i.e., plasmas collected in 105 mM and ISI determined with plasmas collected in 129 mM citrate, or vice versa) we found that an INR of 4.5 could be up to 20% apart from the value that would have been obtained if the appropriate ISI was used. Moreover, if the ISI determined with the manual technique was used to convert PTs obtained with a particular instrument into INR, the effect of citrate concentration was even greater (INR difference up to 64%). Should these observations be valid for other systems, they might provide additional explanations for the frequent reports which document discrepancies in the INR determined with different systems to which incorrect ISI might have been applied. World-wide consensus on a single citrate concentration to collect patients' as well as lyophilized plasmas to be used in External Quality Assessment Schemes and for local system calibration is therefore urgently needed.

Blood Coagulation Tests↗
PubMed1997

Cytokine production patterns in cervical intraepithelial neoplasia: association with human papillomavirus infection.

BACKGROUND: Genital infection with certain strains of human papillomavirus (HPV) is associated with a high risk of malignant transformation, and HPV-associated cervical intraepithelial neoplasia (CIN) can become invasive cancer. Host factors are critical in regulating tumor growth, and cytokines that modulate immunologic control may be of particular importance. The type 1 cytokines interleukin 2 (IL-2) and interferon gamma (IFN gamma) are immunostimulatory and are thus capable of limiting tumor growth. The type 2 cytokines interleukin 4 (IL-4) and interleukin 10 (IL-10) are immunoinhibitory and are thus capable of stimulating tumor growth. PURPOSE: We analyzed the production of cytokines by peripheral blood mononuclear cells (PBMCs) in women with CIN associated with localized or extensively spread HPV infection. METHODS: Thirty women diagnosed with CIN and 10 age- and sex-matched healthy control subjects were enrolled in the study conducted at Istituto Nazionale Tumori, Milan, Italy. The following parameters were analyzed: 1) HPV infection of the cervix and other sites of the lower genital tract by colposcopic, cytologic, and histologic examinations; 2) HPV typing; 3) in vitro production of IL-2 by PBMCs in response to stimulation with soluble antigen (influenza [FLU] antigen) or to cell-associated human leukocyte antigen (HLA) alloantigen; and 4) in vitro production of the type 1 cytokines IL-2 and IFN gamma and of the type 2 cytokines IL-4 and IL-10 by PBMCs in response to mitogen stimulation. Statistical significance was determined by nonparametric tests (two-sided). RESULTS: High-grade CIN associated with HPV infection was detected in all case patients, and HPV type 16 or 18 infection was detected in cervical tissue of 21 (70%) of 30 case patients. HPV infection that had spread to other sites of the lower genital tract, thus resulting in more extensive disease, was detected in 16 (53%) of the 30 individuals with CIN, whereas HPV infection was limited to the portio in 14 (47%). IL-2 production by PBMCs in response to stimulation with soluble antigen or HLA alloantigen was reduced in the group with extensive disease compared with that in the group with localized disease or with that in healthy control subjects. In contrast, IL-4 and IL-10 production in response to mitogen stimulation was elevated in the group with extensive disease compared with that in the group with localized disease or with that in healthy control subjects. The highest production of IL-4 and IL-10 was detected in patients with HPV infection that had extended beyond the genital tract. CONCLUSIONS: CIN is characterized by different immunologic profiles, in which HPV infection is or is not confined to the portio. Production of cytokines that mainly enhance potentially protective cell-mediated immunity is defective in the women in whom extended HPV infection was observed. A pronounced shift from type 1 to type 2 cytokine production is associated with more extensive HPV infection. IMPLICATIONS: These data reinforce the need for detailed analyses of immune dysregulation in CIN patients. They also suggest the potential usefulness of the cytokine assays for determining prognosis or deciding whether cytokine-based therapy is indicated.

Adult↗
PubMed1997

Vaccine strategies: selective elicitation of cellular or humoral immunity?

The discovery of immunoregulatory cytokines and the fact that they modulate the cellular and humoral arms of the immune system, generally in opposing directions raises fundamental questions concerning vaccine development. Because antibiotic-resistance infectious organisms are appearing at an increasingly rapid rate, more emphasis will need to be placed on prevention of infection/disease via immunization and less on post-infection antibiotics. To accomplish this task effectively, immune regulation should be integrated into vaccine design. Here we consider the opposing potentials of cytokine-regulated cellular and humoral immunity, and question whether the "best of both worlds' is possible or desirable.

Animals↗
PubMed1997

A possible role for the cortisol/anticortisols imbalance in the progression of human immunodeficiency virus.

The progression of HIV infection is accompanied by complex alterations in the production of adrenal steroids. Cortisol levels are increased in HIV infection whereas those of dehydroepiandrosterone (DHEA), a physiologic antagonist of the immunoregulatory activities of cortisol, decrease. The progression of HIV infection to AIDS is also characterised by a shift from a type 1 to type 2 cytokine production. Thus, defective production of interferon gamma (IFN gamma), interleukin (IL)-2, and IL-12 as well as increased production of IL-4, IL-5, IL-6, and IL-10 are observed in HIV-seropositive individuals and are proposed to be in vitro immunologic marker of progression. Cortisol and pharmacological doses of glucocorticoids (GC) suppress IL-2 and IFN gamma production and favour the production of IL-4. Furthermore, GC and IL-4 stimulate the differentiation of B lymphocytes into IgE producing plasma cells, the concentration of which augments in HIV infection. Finally, GC induce programmed cell death (PCD) in a variety of different cells, including mature T lymphocytes, and type 2 cytokines were recently proposed to augment the susceptibility of T lymphocytes to PCD. It was suggested that the progressive shift from type 1 to type 2 cytokine production characteristic of HIV infection could be at least partially provoked by the increase in the production of cortisol and the reduction of DHEA. This hypothesis is discussed within the scenario of an endrocrinologic imbalance being responsible for HIV progression at least partially via increased susceptibility of HIV + CD4 lymphocyte to PCD.

Disease Progression↗
PubMed1997

HIV-specific mucosal and cellular immunity in HIV-seronegative partners of HIV-seropositive individuals.

HIV-specific mucosal and cellular immunity was analyzed in heterosexual couples discordant for HIV status in serum and in HIV-unexposed controls. HIV-specific IgA but not IgG was present in urine and vaginal wash samples from HIV-exposed seronegative individuals (ESN), whereas both IgA and IgG were observed in their HIV-seropositive partners; antibodies were not detected in low-risk controls. Envelope protein (Env) peptide-stimulated interleukin-2 (IL-2) production by peripheral blood mononuclear cells (PBMCs) was detected in 9 out of 16 ESNs, 5 out of 16 HIV-infected patients and 1 out of 50 controls. Env peptide-stimulated PBMCs of ESNs produced more IL-2 and less IL-10 compared with those of HIV-infected individuals; no differences were observed in chemokine production or in CCR5 expression. These data demonstrate that a compartmentalized immune response to pathogens is possible in humans and raise the possibility of protective roles for cell-mediated immunity and mucosal IgA in HIV-seronegative individuals exposed to HIV.

Adult↗
PubMed1997

Apoptotic cell death and cytokine dysregulation in human immunodeficiency virus infection: pivotal factors in disease progression.

The progressive loss of CD4 T lymphocyte is patognomonic of Human Immunodeficiency Virus (HIV) infection and results in immunodeficiency and the appearance of acquired immunodeficiency syndrome (AIDS)-defining pathologies. Although a percentage of CD4 T lymphocytes is destroyed directly by HIV infection, a much higher proportion of lymphocytes remains uninfected and therefore must be destroyed by mechanisms not directly involving viral infection. One such mechanism is apoptotic T cell death (ATCD). ATCD in HIV infection has been shown to be: 1) secondary to cross-linking of CD4 by viral proteins; 2) mediated by both APO-1/Fas and lymphotoxin (LT); and 3) differentially modulated by type 1 and type 2 cytokines. We will briefly analyze the experimental evidences suggesting that ATCD contributes significantly to the immunopathogenesis of HIV/AIDS via depletion of CD4+ T cells.

Journal Article↗
PubMed1997

Pentoxifylline improves cell-mediated immunity and reduces human immunodeficiency virus (HIV) plasma viremia in asymptomatic HIV-seropositive persons.

The effects of pentoxifylline on immunologic and virologic parameters were evaluated in 10 human immunodeficiency virus-infected patients not receiving antiretroviral treatment. Patients were asymptomatic, had 300-500 CD4 cells/microL, and received pentoxifylline (1200 mg/day orally) for 4 months. Peripheral blood mononuclear cells were tested before and at five time points during therapy. A transient increase in CD4 cells was observed in 8 of 9 patients, and CD8 cells increased in 7 of 9 patients. These increases were negatively correlated with susceptibility to in vitro mitogen-stimulated apoptotic cell death. Pentoxifylline had a temporary effect on mitogen-stimulated cytokine production; thus, interferon-gamma, interleukin (IL)-2, tumor necrosis factor-alpha, and lymphotoxin increased more than IL-10. Pentoxifylline also potentiated antigen-stimulated IL-2 production and proliferation in 8 of 9 patients and induced significant but transient decreases in plasma viremia in 7 of 9 patients. These preliminary findings suggest that pentoxifylline in vivo has an interesting but temporary influence on both immunologic and virologic parameters.

Adjuvants, Immunologic↗
PubMed1997

Homozygous delta 32 deletion of the CCR-5 chemokine receptor gene in an HIV-1-infected patient.

BACKGROUND: Recent research has found that entry of non-syncytium-inducing (NSI), monocyte-macrophage-tropic HIV-1 isolates requires binding to both CD4 and CCR5 receptors, and that delta 32/delta 32 homozygous individuals are protected against infection. OBJECTIVE: To analyse the polymorphism of CCR-5 gene in HIV-1-infected and uninfected subjects. DESIGN AND METHODS: CCR-5 sequences were amplified by polymerase chain reaction (PCR) from DNA of peripheral blood mononuclear cells. Samples from 152 HIV-1-infected subjects and 122 uninfected controls were tested for the detection of the 32 base-pair deletion. HIV-1 phenotype was determined by viral isolation and MT-2 evaluation. RESULTS: The wild-type/delta 32 heterozygous and delta 32/delta 32 homozygous conditions were represented in 10.7 and 0.8% of healthy controls and in 9.8 and 0.7% of HIV-1-infected subjects, respectively. Of note, the delta 32/delta 32 deletion of the CCR-5 gene was detected by PCR and sequencing confirmed in a patient with progressive infection harbouring a clade B virus with SI phenotype. CONCLUSIONS: delta 32/delta 32 homozygosity for the CCR-5 gene does not confer absolute protection against HIV-1 infection, suggesting that either macrophage-tropic viral strains could use coreceptors other than CCR-5 or infect independently of the presence of a functional CCR-5 coreceptor. Alternatively, primary infection sustained by T-cell-tropic isolates, although exceptional, may occur.

Adult↗
PubMed1997

Long-term resistance to HIV infection in vertical HIV infection: cytokine production, HIV isolation, and HIV phenotype define long-term resistant hosts.

We analyzed immunologic (CD4 and CD8 slopes; interferon-gamma, interleukin-2, interleukin-10, and chemokines production; concentration of IgE; beta 2-microglobulin) and virologic (p24; HIV isolability and phenotype; plasma viremia) parameters in HIV vertically infected children > or = 8 years of age without disease progression or mild symptoms and an absolute CD4+ count > or = 500/microliter with CD4+ percentage > or = 25%. The results were compared to those of two control groups: (1) slow progressors, children > or = 8 years of age with moderate symptomatology and/or moderate CD4 depletion, and (2) progressors, children > or = 8 years of age with severe clinical disease and/or severe CD4 depletion. Pediatric long-term resistant hosts were characterized by higher production of interleukin-2 and interferon-gamma and lower production of interleukin-10, normal concentration of IgE, HIV isolates with a non-syncytium-inducing phenotype, and lower plasma viremia. This condition was not associated with the concentration of beta 2-microglobulin, p24, and chemokines, or with HIV isolability. The IL-10/IL-2 ratio best correlated with both CD4 counts and disease progression. Thus, vertically infected children showing resistance to disease progression are immunologically and virologically distinct from those in whom progressive HIV infection is observed.

Adolescent↗