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Biomedical subjects

C Mancini

Publications and source records attributed to C Mancini.

At least 73 records · Page 4Linked to original sources

Effect of recombinant IL-3 on lymphocyte populations in irradiated mice.

Administration of murine recombinant interleukin 3 (IL-3) to sublethally irradiated mice induced in the thymus recovery of the cell count and mitotic responsiveness to Con A, as well as a decrease in CD4-CD8- cells concomitant with an increase in single positive cells. Also in the spleen, the cell count and mitotic responsiveness to Con A and lipopolysaccharide (LPS) were recovered by IL-3 treatment. These findings show that IL-3 induces differentiation and growth of thymocytes and recovery of T and B cell functions in sublethally irradiated mice.

Animals↗

Detection of antibodies to hepatitis C virus in dialysis patients.

Dialysis patients are at risk for infection by a variety of blood-borne agents transmitted within dialysis units. The development of the hepatitis C virus (HCV) screening test prompted many studies on the prevalence of anti-HCV among dialysis patients. The authors have evaluated the prevalence of anti-HCV in 405 hemodialysis patients both by Elisa screening and 4-RIBA test system with a follow-up of two years. The study showed a difference in the incidence of antibodies to HCV by year. In 1990, 15.2% were positive with an increase to 20.8% in 1991. There was an increase of 5% in dialysis patients and only 1.9% in the personnel working in the dialysis ward. Another control group of volunteers did not show any positivity. In addition, the correlations of the antibodies against HCV with markers of hepatitis B virus (HBV) and history of transfusion were evaluated. These findings suggest that the patients found to be positive should be dialyzed on separate machines and special precautions must be undertaken to reduce the risk of transmission.

Adult↗

Differential effect of human and murine polyclonal and monoclonal antisera on TNF-alpha production by human monocytes.

The capacity of human and murine polyclonal and monoclonal antibodies to inhibit lipopolysaccharide (LPS)-induced tumor necrosis factor-alpha (TNF-alpha) release from human monocytes was investigated. Human pooled immunoglobulin G (IVIG), human IgM monoclonal antibody (HA-1A) directed against the lipid A moiety of LPS, and murine IgG monoclonal antibody (MT-1F) raised in mice against antibiotic-treated Escherichia coli O6:K- were either added simultaneously with LPS to monocytes or preincubated for 1 h at 37 degrees C before being added to monocytes. TNF-alpha content in the monocyte supernatants was then tested. Simultaneous addition of increasing concentrations of IVIG (from 0.3 to 2.5 mg/ml) and 10 micrograms/ml of LPS to monocytes induced an enhanced release of TNF-alpha by monocytes in a dose dependent fashion. Preincubation of IVIG with LPS abolished the additive effect, but did not inhibit LPS-induced TNF-alpha release by monocytes. The simultaneous addition of LPS and HA-1A to monocytes had no additive effect nor did it inhibit TNF-alpha release. On the other hand, inhibition of TNF-alpha release was observed when HA-1A was preincubated with LPS before being added to monocytes. In all instances MT-1F inhibited TNF-alpha release when the monocytes were stimulated with smooth type LPS, but not with LPS isolated from rough mutants.

Animals↗

Reactivity and protective capacity of a polyclonal antiserum derived from mice immunized with antibiotic exposed Escherichia coli.

The murine immune response to Escherichia coli O6:K-alone or pre-exposed to 0.1 x MIC of aztreonam was investigated. Relative to mice immunized with untreated bacteria, mice immunized with antibiotic-treated microorganisms presented a significantly enhanced protection towards a challenge of 100 x LD50 of viable E. coli O6:K-. Previous injection of 0.1 mL of serum drawn from mice immunized with treated and untreated bacteria protected non-immunized mice towards a challenge of 10 x LD50 of viable E. coli O6:K--. Serum from mice immunized with treated bacteria also protected non-immunized mice towards a lethal challenge of E. coli O111. The antiserum contained high titre of IgG antibodies that cross-reacted with lipopolysaccharide isolated from smooth and rough Gram-negative bacteria. Immunoblotting showed additional bands of reactivity to the untreated E. coli O6:K-. Immunization with antibiotic-treated bacteria led to the production of type specific and cross reactive antibodies that protected animals against viable homologous and heterologous lethal challenges.

Animals↗

Preincubation of Candida albicans strains with amphotericin B reduces tumor necrosis factor alpha and interleukin-6 release by human monocytes.

The release of tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6) by human monocytes stimulated with whole heat-killed Candida albicans CA3 (a clinical isolate) and CA2 (a germ tube-negative mutant) either treated or not treated with amphotericin B was investigated. The optimal release of the cytokines was observed at 24 h of incubation of the yeasts with the monocytes for both TNF-alpha and IL-6. The levels ranged from 10,500 to 19,000 U/ml for TNF-alpha and from 350 to 460 pg/ml for IL-6. Germ tube-negative mutant CA2 induced the release of TNF-alpha at levels significantly (P < 0.05) lower than those induced by clinical isolate CA3, while no major differences were observed between the two strains with regard to their capacity to induce the release of IL-6. In all instances, preincubation of the yeasts with a sublethal concentration of amphotericin significantly reduced cytokine production. These results suggest that drug-induced alterations of fungal outer structures may affect the interactions between the yeasts and the monocytes, resulting in a reduced level of secretion of cytokines.

Amphotericin B↗

Tumor necrosis factor alpha (TNF-alpha) production in mice immunized with Escherichia coli: correlation with mortality after lethal challenge and production of a native inhibitor of TNF-alpha activity.

The kinetics of tumor necrosis factor alpha (TNF-alpha) production, the correlation between cytokine levels and mortality rates after lethal challenge, and the production of a native inhibitor of TNF-alpha activity was investigated in mice immunized with formalin-killed Escherichia coli. Groups of mice were injected for 8 weeks with either untreated bacteria or bacteria treated with 0.5 MIC of aztreonam and subsequently challenged with 100 50% lethal doses of viable E. coli. Mice receiving saline only (controls) died within 24 h. The mortality of mice immunized with aztreonam-treated E. coli was significantly lower than that of mice immunized with untreated E. coli. There were no measurable levels of TNF-alpha in sera obtained from control mice during the entire period of immunization. TNF-alpha levels ranging from 90 to 306 U/ml were measured 90 min after each vaccination in sera obtained from mice immunized with untreated E. coli. Sera from mice immunized with antibiotic-treated E. coli showed lower TNF-alpha levels, ranging from 40 to 128 U/ml. TNF-alpha levels measured 90 min after lethal challenge correlated with the mortality rate observed in each group (r = 0.95). The cytotoxic activity of recombinant murine TNF-alpha was inhibited by the sera from immunized mice but not by the sera from controls. The inhibition was drastically reduced by preincubation of the sera with staphylococcal protein A. In immunoblot experiments, class G immunoglobulins reacting with recombinant murine TNF-alpha were observed in the sera of immunized mice. These data confirm the correlation existing between TNF-alpha levels and mortality and suggest that native inhibitors may play a role in the regulation of the biological function of the cytokine.

Animals↗

Effect of intravenous immunoglobulin on opsonic activity and TNF production in patients at high risk for sepsis syndrome.

In a randomized double blind study, we analyzed the efficacy of IVIG in the infectious complications in patients at high risk of developing sepsis syndrome. Two groups of twenty patients were enrolled, one receiving 250 mg/Kg of IVIG on the first and seventh day after admission and the other receiving sterile saline as placebo. Serum samples were drawn before IVIG administration and 24, 48 and 72 hours afterwards. The same schedule was used for patients treated with placebo. Sera pooled from healthy donors served as controls. On all the samples, opsonic and bactericidal activity as well as C3, total IgG and serum TNF content were tested. IVIG did not significantly affect total IgG and C3 content. Similarly, opsonic and bactericidal activity tested against E. coli 06 :K-, E. coli 0111 and SAC I was not modified ranging within HPS values. Furthermore, IVIG administration did not change the TNF level. A lower incidence of bacteremia in IVIG treated patients was observed.

Blood Bactericidal Activity↗

Culture filtrates and whole heat-killed Candida albicans stimulate human monocytes to release interleukin-6.

The release of interleukin-6 (IL-6) by human monocytes upon stimulation with culture filtrates and heat-killed Candida albicans cells was studied. Two strains of C. albicans (a wild strain CA3 and an agerminative mutant CA2) were cultured overnight at 28 degrees C in complete medium, and 10(6) cells/ml were either filtered at different time points (6, 12, 18, 24, 30 hours) or heat-killed. C. albicans preparations were then added to monolayers of monocytes isolated from healthy donors and incubated at 37 degrees C in 5% CO2 atmosphere. Cell culture supernatants were collected at different time points (every 6 hrs for 30 hrs), and IL-6 content was then measured by immunometric assay. Monocytes stimulated with heat-killed C. albicans cells released IL-6 in the supernatants with values ranging from 59 to 460 pg/ml, that peaked at 24 hrs of incubation. Using heat-killed whole cells of C. albicans no major differences were observed between the two strains used in their capacity to induce IL-6. Culture filtrates also stimulated monocytes to release IL-6 and maximal cytokine levels were observed when the monocytes were triggered with filtrates from yeasts cultured for 24 hours. CA2 filtrate induced IL-6 levels to an extent significantly higher than did CA3 filtrate. These data add further evidence to the immunomodulatory properties possessed by structures of C. albicans.

Candida albicans↗

Fluoxetine efficacy in social phobia.

BACKGROUND: To determine the efficacy of fluoxetine in the treatment of social phobia, fluoxetine was administered to 16 patients with a primary DSM-III-R diagnosis of social phobia in a 12-week, open, clinical trial. METHOD: Treatment began at 20 mg of fluoxetine daily and was increased according to clinical response and side effects every 4 weeks. Patients completed self-report measures of anxiety and depression at baseline and at Weeks 4, 8, and 12. These included the Beck Depression Inventory, the Social Avoidance and Distress Scale, the Fear of Negative Evaluation Scale, the State-Trait Anxiety Inventory, the Fear Questionnaire, the Social Anxiety Thoughts Questionnaire, and the Social Adjustment Scale-Self-Report. Clinicians completed a Clinical Global Improvement Scale. RESULTS: Thirteen of the 16 patients completed the trial. Three patients (18.8%) were unable to complete the trial due to adverse side effects. Of the 13 (81.2%) remaining patients, 10 were considered to be responders and 3 were considered to be nonresponders. Measures of social anxiety and phobic avoidance showed a significant improvement from baseline to endpoint, achieving a significance of p < .005. Responders to fluoxetine were more likely to have been older at onset of the social phobic symptoms and had a shorter duration of illness. CONCLUSION: These findings suggest that fluoxetine may be effective in the treatment of social phobia. Double-blind studies will be required to further investigate these findings.

Adult↗

Urinary catecholamines and cortisol in parasuicide.

A relationship of urinary catecholamines and of urinary free cortisol with violent suicide attempts has been reported. We have reexamined this issue in patients within 24 hours of hospital admission. Suicide attempters had significantly higher norepinephrine (NE: mean +/- SD = 58.3 +/- 27.0 micrograms/24 hours; n = 27) than did control patients with suicidal ideation (mean +/- SD = 37.1 +/- 21.3; n = 10). Among suicide attempters, those who used physical means had the highest NE levels (mean +/- SD = 69.7 +/- 21.3) and those who took overdoses of antidepressants (mean +/- SD = 51.9 +/- 17.3; n = 6), benzodiazepines (mean +/- SD = 65.1 +/- 29.7; n = 5), or miscellaneous drugs (mean +/- SD = 59.1 +/- 36.5; n = 11) had lower NE values. In contrast to NE, urinary dopamine (mean +/- SD = 402.6 +/- 392 micrograms/24 hours, epinephrine (EPI: mean +/- SD = 14.3 +/- 4.0 micrograms/24 hours), the NE/EPI ratio (mean +/- SD = 8.3 +/- 0.9), urinary free cortisol (mean +/- SD = 157.9 +/- 11.5 micrograms/24 hours) and serum cortisol (mean +/- SD = 35.0 +/- 13.1 nM/l) did not differ between groups. There were no group differences in age (mean +/- SD = 36.3 +/- 16.5 years), Beck Depression Inventory score (mean +/- SD = 26.3 +/- 12.9), Beck Hopelessness Scale score (mean +/- SD = 10.0 +/- 5.6), Beck Scale for Suicidal Ideation score (mean +/- SD = 13.6 +/- 9.3), or Hamilton Rating Scale for Depression score (mean +/- SD = 19.5 +/- 9.8). In the four parasuicide groups, there was no difference in suicide intent (mean +/- SD = 13.3 +/- 7.9). These findings indicate that there is increased NE output shortly after suicide attempts. Previous reports of a low NE/EPI ratio in suicidal patients may reflect adaptive changes rather than the acute state of the patient at the time of the attempt.

Adult↗

Relationship of social phobia with other psychiatric illness.

Fifty-seven social phobic patients were studied to identify the comorbidity with other psychiatric illnesses and their temporal relationships. Mood disorders, particularly major depression, was the most common other lifetime diagnosis (70.2%). A large majority (70.2%) suffered from, at least, one other anxiety disorder in their lifetime and, in particular, panic disorder with or without agoraphobia (49.1%). Alcohol (28.1%) and substance (15.8%) abuse or dependence were also common lifetime diagnoses. Social phobia usually predated any episode of mood disorder (81.7%) or any other anxiety disorder (62.7%). Social phobia may predispose individuals to other psychiatric illnesses, in particular major depression.

Adolescent↗

Immunization of mice with antibiotic treated Escherichia coli.

The hypothesis of a different immunogenicity between untreated and antibiotic-treated Escherichia coli was investigated in vivo. Groups of mice were injected weekly for eight weeks with formalin-killed E. coli ATCC 25922 either exposed or not to 0.1 x MIC of aztreonam. A group of mice injected with sterile saline only served as control. IgG production towards whole bacteria was clearly enhanced in the group immunized with antibiotic-treated E. coli as shown in ELISA assays. In the same group, the appearance of additional bands of reactivity in the region of major outer membrane proteins was observed in immunoblot experiments as well as an enhanced protection towards a challenge of 10 x LD50 of live E. coli. These findings seem to support the hypothesis that sub-MICs of antibiotics modify the bacterial surface influencing host-parasite relationships.

Animals↗

Effect of cyclosporin A on B cell maturation and differentiation.

The activation and differentiation of resting B cells into Ig secreting cells are regulated by T cells, macrophages and their secreted factors. The present study evaluated the effect of cyclosporin A (CsA) on this process. Peripheral blood lymphomonocytes (PBMC) drawn from healthy donors were stimulated with protein A (PA) or with lipopolysaccharides plus pokeweed (LPS+PWM) in either the presence or the absence of CsA. Phenotypic B cell changes and immunoglobulin production was then analyzed. The data revealed that CsA decreased the expression of B cell surface receptors of the activation phase, and enhanced the resting phase receptors. Different effects of CsA were found on B cell differentiation, depending on its induction by PA or LPS+PWM. In the first system, CsA decreased the expression of differentiation phase receptors and the secretion of free Ig. In cultures stimulated with LPS+PWM, CsA increased the differentiated phase receptors and Ig secretion. Thus, CsA seemed to act as a blocking agent of the activation phase and as a modulator of the differentiation phase and of IgG secretion, depending upon the antigen used for stimulation.

Antigens, Surface↗

Age-related changes within a suppressor T cell circuit.

The effects of aging on cellular and molecular components of the 4-hydroxy-3-nitrophenyl acetyl-specific suppressor T (Ts) cell circuit were analyzed in vitro using inducer (Ts1), transducer (Ts2), and effector (Ts3) cells and activating factors (TsF1 and TsF2) derived from young or old mice. The activation of Ts2 cells by TsF1 and of Ts3 cells by TsF2 was found age-restricted, suggesting a loss of Ts2 and Ts3 cell subsets in old mice. However, the activation of Ts3 cells by small amounts of TsF2 is more efficient when both are derived from old rather than from young mice while the same level of maximum suppression is attained. Higher affinity of the interactions involved in Ts cell activation may compensate for loss of Ts cell subsets in old mice. No age restriction was found for antigen presentation to Ts1 cells and for the interaction between Ts3 cells and target B cells. Thus, the effects of aging on immunosuppression result from changes within the Ts cell circuit.

Aging↗

An Apple IIE microcomputer program for multiple non-independent comparisons by the Scheffe's test.

When more than two groups of observations from the same set of experimental data are compared and pairwise tested for equality of their means, appropriate statistical treatment of the data is required. The overall variation in the set of data must be considered, and also the statistical non-independence of each pairwise comparison must be taken into account. We describe a simple Apple IIE microcomputer program that applies the Scheffe's test for multiple comparisons. A numerical example and a sample output of this program are also included. The listing of the program is reported in the Appendix.

Analysis of Variance↗