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Biomedical subjects

E Jirillo

Publications and source records attributed to E Jirillo.

At least 145 records · Page 8Linked to original sources

Exaggerated spontaneous release of tumor necrosis factor-alpha/cachectin in patients with migraine without aura.

Serum levels of tumor necrosis factor (TNF)-alpha/cachectin have been evaluated in 20 patients with Migraine without Aura (MwA) versus 17 patients with Chronic Type Tension Headache (CTTH). Results show an exaggerated release of TNF-alpha/cachectin in sera of patients affected by MwA, while in CTTH patients TNF serum concentration is comparable to that observed in normal donors. Some hypotheses are formulated in order to clarify the TNF-alpha/cachectin spontaneous production and its biological significance in patients with MwA.

Adult↗

Mitochondrial F0F1 H+-ATP synthase. Characterization of F0 components involved in H+ translocation.

The membrane F0 sector of mitochondrial ATP synthase complex was rapidly isolated by direct extraction with CHAPS from F1-depleted submitochondrial particles. The preparation thus obtained is stable and can be reconstituted in artificial phospholipid membranes to result in oligomycin-sensitive proton conduction, or recombined with purified F1 to give the oligomycin-sensitive F0F1-ATPase complex. The F0 preparation and constituent polypeptides were characterized by SDS-polyacrylamide gel electrophoresis and immunoblot analysis. The functional role of F0 polypeptides was examined by means of trypsin digestion and reconstitution studies. It is shown that, in addition to the 8 kDa DCCD-binding protein, the nuclear encoded protein [(1987) J. Mol. Biol. 197, 89-100], characterized as an intrinsic component of F0 (F0I, PVP protein [(1988) FEBS Lett. 237,9-14]) [corrected] is involved in H+ translocation and the sensitivity of this process to the F0 inhibitors, DCCD and oligomycin.

Animals↗

Humoral and cellular immune responses to Salmonella typhi in patients with typhoid fever.

Humoral and cellular immune responses to Salmonella typhi have been studied in nine children with typhoid fever. By using dot immunobinding assay, anti-O-polysaccharide chain and antilipid A antibody titers have been evaluated during the course of the disease. Anti-O-polysaccharide chain antibody titers are lower at the first week and increase up to the third week of the infection. On the other hand, antilipid A antibody levels, which are already higher at the beginning of the disease, progressively augment during the following weeks. Concerning cellular immunity to S. typhi, antibacterial activity mediated by typhoid peripheral mononuclear cells has been determined. Results show this function to be depressed in the initial phase of typhoid, increasing with the time. Together, these data bring new insight on immunity in typhoid patients.

Antibodies, Bacterial↗

Effects of substance P on the spontaneous binding of Salmonella minnesota R345 (Rb) to human peripheral blood lymphocytes.

The effects of substance P (SP) on Salmonella minnesota R345 (Rb) binding to human peripheral blood lymphocytes (PBL) were evaluated. Two parameters of bacterial cytoadherence were considered, namely the binding lymphocytes (BL) and the number of bound-bacteria/lymphocyte (BB). The results showed that SP inhibits both BL and BB in a significant manner. Furthermore, distribution of Salmonella binding to CD4+ and CD8+ lymphocytes was studied following SP pretreatment of lymphoid cells. This neuropeptide is able to hamper the bacterial cytoadherence to both T-cell subpopulations and, in particular, the inhibitory effect on the T-suppressor/cytotoxic subset was more pronounced. These findings are discussed in terms of SP intervention in the mechanism of host protection against invading microorganisms.

Antigens, CD↗

Increased production of interleukin-2 and IL-2 receptor in primary IgA nephropathy.

The production of interleukin-2 (IL-2) by peripheral blood mononuclear cells (PBMC) in 13 patients with IgA nephropathy (IgAN) and 9 patients with chronic glomerulonephritis was investigated. Moreover, the distribution of IL-2 receptor (IL-2R) expression was studied in the purified T cell population versus the non-T cell population of IgAN patients. The results show a spontaneous significant production of IL-2 in cultures of PBMC from patients with IgAN (P less than 0.025) that increased after PHA stimulation. IgAN patients also had a significantly higher expression of IL-2R on the surface of PBMC than did patients with chronic glomerulonephritis (P less than 0.05). IL-2R was usually detected on unstimulated purified T cells that expressed the activation DR antigen. Moreover, a high number of DR helper T cells was associated to a reduced number of suppressor T cells (OKT8+M1+). These findings suggest that the increased production of IL-2 in patients with IgAN may be responsible for the increased activity of helper T cells. The high number of IL-2R expressed by freshly separated PBMC implies an in vivo continuous stimulation of these cells, and this finding is in agreement with the demonstrated spontaneous hyperproduction of IL-2. Moreover, the low number of suppressor T cells may contribute to the overactivity of helper T cells bearing IL-2R in IgAN patients.

Adult↗

Diazepam inhibits phagocytosis and killing exerted by polymorphonuclear cells and monocytes from healthy donors. In vitro studies.

The effect of a benzodiazepine (BDZ), diazepam on human polymorphonuclear cell (PMN) and monocyte phagocytosis and killing from healthy volunteers has been evaluated. Diazepam is able to inhibit in vitro both functions exerted by PMN and monocytes at 10(-5) and 10(-6) M concentrations/ 4 x 10(6) phagocytes. 10(-7) M concentration was not effective in all the instances. These results are discussed for their possible clinical implications, since previous studies have shown that in patients with phobic disorder there is evidence for reduced phagocytosis and killing capacities.

Adult↗

Monocyte- and cytokine-mediated effects on T immunoregulatory activity in the elderly.

Aged individuals exhibit an impairment of T helper and/or T suppressor activity on B cell function in an antibody-specific induction system. Further evidence is now provided that soluble suppressive factors acting on monocytes play a key role in such deficits. In fact, overnight preincubation of isolated monocytes and supplementation of autologous lymphocytes reverses the immunoregulatory imbalance. The suppressive factors are also responsible for a decreased interleukin 2 (IL-2) synthesis since a similar pretreatment of cell suspensions or exogenous human IL-1 and/or IL-2 supplementation of aged cell cultures leads to a recovery of T regulatory effects on B cell differentiation. Similar effects are observed in the presence of thymopentin, a well known IL-2 inducer. Interferon alpha and gamma addition to cultures gives rise to a restoration of T immunoregulatory effects. These findings suggest that several mechanisms are involved in the depressed T immunoregulatory activity in the elderly.

Aged↗

Topological and functional characterization of the F0I subunit of the membrane moiety of the mitochondrial H+-ATP synthase.

Using isolated polypeptides of the F0 sector of bovine heart mitochondrial H+-ATPase, antisera were developed detecting specifically two components of F0. These two components were identified as F0I and oligomycin-sensitivity-conferring protein (OSCP) respectively. Both F0I and OSCP were digested by mild trypsin treatment of submitochondrial particles depleted of the catalytic part of H+-ATPase (USMP). Proteolysis was largely prevented by binding of F1 to F0. Proteolysis of F0I resulted in the formation of three immunoreactive, membrane-bound fragments of apparently 26 kDa, 25.5 kDa and 18 kDa, respectively, indicating that F0I contains trypsin-accessible Arg or Lys residues located close to the end and the middle part of the protein, respectively, which are in intimate contact with F1. Digestion of USMP with trypsin resulted in depression of passive H+ conduction through F0 which could be ascribed to proteolysis of F0I.

Animals↗

Evaluation of procoagulant activity production and other coagulative functions in cancer patients receiving acid treated Salmonella minnesota R 595 (Re).

Blood clotting parameters were measured in six patients with gynecologic tumors following i.v. administration of acetic acid-treated Salmonella minnesota R595 (Re), which has been previously demonstrated to enhance impaired immune functions in the same patients. Although these bacteria possess a more exposed lipid A at their surface which has the potential to stimulate the coagulative cascade, no evidence of plasma hypercoagulative state was detected. In fact, procoagulant activity generated by patients' mononuclear cells after Salmonella treatment was not significantly higher than that produced by patients' cells before treatment. Moreover, other haemostatic laboratory parameters were unaffected by in vivo treatment with bacteria.

Acetates↗

Anti-bacterial activity mediated by human platelets.

Platelet-mediated antibacterial activity against gram-negative microorganisms has been investigated. Data show that human washed platelets possess the ability to partially inhibit growth of Salmonella typhi Ty-2 (a smooth strain) but not of two rough strains of Salmonella minnesota (R345-Rb and R595-Re). On the other hand, no antibacterial activity was noted in the presence of the gram-positive Staphylococcus aureus. This activity is dependent on the length of incubation of platelets with bacteria and apparently is not mediated by platelet soluble factors. Finally, lysis of platelets with Triton X-100 following their incubation with bacteria gives rise to the same degree of antibacterial activity observed in the untreated samples. This implies that the described platelet function does not rely on the possible trapping of bacteria in platelet aggregates.

Blood Platelets↗

Inhibition of lymphocyte-mediated antibacterial activity by human seminal plasma.

Seminal plasma displays a suppressive function on many immunological responses. In light of recent findings on the antibacterial activity mediated by different lymphocyte subsets, we have assessed the effect of male inhibitory material (MIM) in this system. Results provide evidence that MIM pretreatment of peripheral blood lymphocytes (PBL) leads to a significant inhibition of antibacterial activity against Salmonella typhi and S. minnesota R345 (Rb). Both CD4+ and CD8+ cell-mediated activities are reduced by this treatment, while another defense mechanism (bacterial binding to PBL) is unaffected. Taken together, these results indicate a role for MIM in the depression of immune response and suggest that lymphocytes mediating antibacterial activity and bacterial cytoadherence are different entities.

Blood Bactericidal Activity↗

Enhancement of host resistance against Salmonella typhimurium infection by a diet supplemented with yogurt.

The effect of a diet supplemented with yogurt containing live lactobacilli (LAB) - Lactobacillus bulgaricus and Streptococcus thermophilus - on the response of inbred mice to infection with Salmonella typhimurium was elaborated. The results of our experiments were consistent with the hypothesis that modifications of the microflora influence the adherence of S. typhimurium to intestinal mucosa, the natural antibacterial activity of the Peyer's patches lymphocytes, the accumulation of the macrophages in the liver, the proliferative responses of the splenocytes. The relationship between modifications of the immune response following ingestion of yogurt with live LAB and increased defense mechanisms was confirmed by the bacterial counts in livers and spleens and by the reduced mortality to S. typhimurium infection.

Animals↗

Interactions of lymphocytes with bacterial antigens.

Several observations indicate that smooth (S) and rough (R) Salmonella strains display the capacity to spontaneously adhere to lymphoid cell membrane. Such a phenomenon is confined to T lymphocytes and affects both CD4+ and CD8+ cells. As far as receptor structures on lymphocytes surface are concerned, the lipopolysaccharides (LPS) of the bacterial cell wall play a key role in human and murine cytoadherence. In addition, evidence has been provided that LPS of gut flora induce bacterial binding as assessed by the evaluation of cyto-adherence at different anatomical sites. Interestingly, cells mediating nonspecific immune responses are not involved in the bacterial binding, since the unbound fraction is highly enriched for cytotoxic and T helper cells. The in vivo occurrence of binding in typhoid fever patients suggests that this activity may represent an earlier event during the course of infection. These findings are also supported by the demonstration that chemotherapeutic treatment abolished bacterial binding in both vitro and in vivo systems. Finally, the production of lymphokines following bacterial stimulation points out the importance of bacterial/immune system interaction in the development of immune response during gram-negative sepsis.

Antigens, Bacterial↗

Adherence of specific yogurt micro-organisms to human peripheral blood lymphocytes.

Yogurt lactic-acid-bacteria (LAB) consisting of Lactobacillus bulgaricus and Streptococcus thermophilus were evaluated for their capacity to bind to human peripheral blood lymphocytes (PBL). These micro-organisms adhere to human T lymphocytes, and bind to B lymphocytes, in high and low frequencies, respectively. In addition, a quantitative analysis of LAB binding to PBL was carried out using the same parameters previously applied to a Salmonella model. The effect of yogurt LAB on the natural anti-bacterial activity exerted by PBL was examined. Lymphocyte pretreatment with bacteria did not affect such functions. These findings are discussed in the light of the well known ability of yogurt LAB to modulate the immune response.

B-Lymphocytes↗

Immunoresponsiveness in hemophilia: lymphocyte- and phagocyte-mediated functions.

Several deficits of immune response have been reported in hemophiliacs. In order to evaluate the overall immune function in this disease, we have investigated peripheral blood mononuclear cells (PBMC) surface phenotype, lymphokine production, B cell responsiveness, monocyte- and polymorphonuclear (PMN) cell-mediated responses in a group of 25 A or B hemophiliac patients. They were treated with concentrates (greater than 30,000 U/year) for at least 8 years, and ten of them were positive for human immunodeficiency virus (HIV) infection. With particular reference to lymphocyte surface markers, a low CD4+/CD8+ ratio and an increased frequency of CD25+ and surface immunoglobulin (sIg) positive lymphocytes were noted in HIV+ subjects. By contrast, CD3+ and CD4+ cell frequency was decreased in HIV- patients, whereas in the same individuals CD11+ and sIg+ cell percentage was augmented. Regardless of HIV infection, a quite variable degree of B-cell response was seen in hemophiliacs with either a T-independent or a T-dependent polyclonal B cell activator. PMN chemotaxis, phagocytosis, and killing were significantly diminished, whereas similar monocyte functions were basically unaffected. Finally, hemophiliacs were characterized by a profound impairment of leukocyte inhibiting factor (LIF) and lymphocyte-derived chemotactic factor (LDCF) production. Our findings clearly indicate an impairment of immune function in hemophiliacs regardless of HIV infection.

Adolescent↗