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Biomedical subjects

V Zakuth

Publications and source records attributed to V Zakuth.

At least 19 recordsLinked to original sources

Procalcitonin correlates with C-reactive protein as an acute-phase reactant in pediatric patients.

BACKGROUND: Previous reports on the behavior of procalcitonin blood levels in diverse clinical conditions suggest that it is part of the activation of cellular immunity and is another acute-phase reactant. OBJECTIVE: To compare procalcitonin with C-reactive protein, a well-known acute-phase reactant, in a series of acutely febrile pediatric patients and to review recent literature on procalcitonin. METHODS: Procalcitonin and CRP levels were evaluated in 38 blood samples of pediatric patients who were admitted to the Dana Children's Hospital for evaluation of unexplained fever or for sepsis work-up. RESULTS: The parallelism between procalcitonin and CRP was found to be highly significant (P < 0.01). CONCLUSION: The rise of procalcitonin blood levels in febrile pediatric patients suggests that it is part of the acute-phase reaction, parallel with the CRP reaction.

Acute-Phase Reaction↗

Increased apoptosis in patients with major depression: A preliminary study.

Apoptosis is a programmed cell death that can be observed in normal cells. Major depression poses a combination of a depressed and destructive autoimmune reaction. We measured apoptosis in the PBLs of seven patients with major depression and in age- and sex-matched controls. We observed significantly increased apoptosis in the PBLs of depressive patients (p < 0.05). These preliminary results could contribute to an understanding of the interactions of the CNS with the immune system, which could lead to the increased vulnerability of the CNS in depressive disorders. Further studies are needed to establish these results.

Adult↗

Immune activation in non-treated suicidal major depression.

In the following study we have analyzed cytokine secretion of T-cells of suicidal and non-suicidal depressed patients and healthy controls. It was found that T-cells of suicidal depressed patients have Th1 characteristics, while T-cells of non-suicidal depressed patients have Th2 characteristics. Th1 environment is associated with most of autoimmune diseases. It is thus speculated that Th1 activation in suicidal depression may reflect a unique form of autoimmune suicide.

Cytokines↗

[Decreased interleukin-1 and interleukin-2 production after splenectomy].

Production of interleukin-1 and of interleukin-2 was measured in 57 splenectomized patients. 11 of them were after elective operations (aged 14-37 years, mean 24) and 46 posttraumatic (aged 20-36, mean 23) and in 20 appropriate controls. There was significant reduction of both interleukins in the splenectomized group, more evident in the elective group. The deficiency was not related to age of patient or time since splenectomy. These results support the view that a consequence of splenectomy is immunoregulatory deficit.

Adolescent↗

Phenotypic and functional profile of peripheral blood mononuclear cells isolated from melanoma patients undergoing combined immunotherapy and chemotherapy.

In the present study we tested the phenotypic profile as well as several immunological responses of peripheral blood mononuclear cells (PBMC) isolated from melanoma patients. These patients underwent chemotherapy with dacarbazine and carboplatin from day 1 to day 22, followed by immunotherapy of low-dose recombinant interleukin-2 and recombinant interferon alpha administered subcutaneously from day 36 to day 75. The PBMC from 14 patients were isolated on day 0 before chemotherapy, on day 36 after chemotherapy and on day 76 after immunotherapy. After chemotherapy, a decrease in CD16+ cells and increase in CD3+ and CD4+ cells correlated with a significant decrease in the generation of lymphokine-activated killer (LAK) activity. After immunotherapy, an increase in CD16+ cells correlated with an increase in the induction of LAK activity. A comparison between responding and non-responding patients revealed statistically significant differences in LAK activity of PBMC and response to concanavalin A following chemotherapy, and in the percentage of CD8+ cells following immunotherapy. Our results point toward the value of continuing such a study on a larger population of cancer patients in order to select the appropriate bioassays for monitoring and predicting the clinical responsiveness to combined therapies.

Adult↗

Reduction of circulating HIV antigens in seropositive patients after treatment with AL-721.

Sixteen patients seropositive for human immunodeficiency virus (HIV) at different stages participated in an open trial using the lipid mixture AL-721. Seven patients were antigen negative and asymptomatic and the other nine antigen positive, three of whom were virtually asymptomatic. AL-721 was given per os once a day at a dose of 10 g in a fat-free breakfast for up to 16 months. The presence of HIV antigens in the serum was monitored by enzyme immunoassay (EIA) using two commercial kits. In five of the nine antigen-positive patients the concentration of HIV antigens was reduced to basal level after about 3 months of AL-721 treatment; three of these responders were asymptomatic, one had persistent generalized lymphadenopathy, and the other had Kaposi's sarcoma. In one of the antigen-positive patients who did not respond to AL-721, the addition of AZT to the treatment resulted in a marked decrease in antigen level. Another AIDS patient receiving this combination therapy from onset of the trial showed a similar decrease. The other two nonresponding patients were at a stage of full-blown AIDS. These results suggest that AL-721, an innocuous compound, may be effective in reducing the serum HIV level in patients at the preclinical stage.

Adult↗

Tuftsin stimulates IL-1 production by human mononuclear cells, human spleen cells and mouse spleen cells in vitro.

Human peripheral adherent cells from splenectomized subjects, human spleen cells and mouse spleen cells were tested for IL-1 production in vitro in presence or absence of synthetic tuftsin (Thr-Lys-Pro-Arg). Application of synthetic tuftsin to peripheral blood adherent cells from normal donors as well as from splenectomized subjects induces IL-1 production. In splenectomized subjects the extent of induction was more evident than in controls. In human splenic cells tuftsin stimulates IL-1 production without KLH or LPS. In mouse spleen cells tuftsin alone did not stimulate the IL-1 secretion. However, addition of tuftsin to mouse spleen cells incubated with KLH augmented significantly the IL-1 secretion. As removal of the spleen leads to tuftsin deficiency, our present findings may perhaps explain the fulminant nature of the postplenectomy sepsis and some immune disturbances described in the postplenectomy state.

Animals↗

The immune system response to Campylobacter infection.

Campylobacter may be one of the most common causes of bacterial gastroenteritis (GE) in children. It has recently been suggested that it is one of the bacterial pathogens most likely to infect immune-compromised children, and it may facilitate colonization of enteric pathogens. The immune system response was studied in 12 children with Campylobacter fetus subspecies jejuni (CBJ) infections. Serum concentrations of IgA, IgM, and IgG were analyzed using a Beckman auto-analyzer. Sera specific Ab to CBJ were tested with CBJ specific enzyme-linked immunosorbent assay (ELISA). Mitogen stimulation of lymphocytes was performed to three lectins: Con A, PWM, and PHA. The lymphocyte blast transformation to Campylobacter was studied using the Campylobacter antigen. T-cell subsets were studied using the monoclonal antibodies Leu 2, 3, and 4 (Becton Dickinson). Chemotaxis was measured in modified Boyden chambers; chemotactic stimulants were the Formyl Met Leu Phe, Campylobacter antigen virion, and E. coli 0111 B. Immunoglobulins were normal in nine cases and abnormal in two children previously diagnosed as agammaglobulinemic and one diagnosed as hypoagammaglobulinemic. Specific serum Ab level was significantly higher in the CBJ group, except in the agammaglobulinemic group. Stimulation indices to mitogens and monoclonal subset were in the normal range. The blastogenic transformation to CBJ Ag was decreased compared to normal lectins, and positive and high compared to controls. The chemotactic activity to campylobacter Ag was decreased in comparison to other stimulants. Most CBJ infections are self-limiting due to a normal immune response and collaboration of all cellular limbs. When, however, the immune response is disturbed, we may find a prolonged and complicated course of CBJ.

Antibodies↗

The immune regulation in familial Mediterranean fever (FMF).

In order to investigate a possible immune regulation imbalance in familial Mediterranean fever (FMF), the T-cell subsets and interleukin (IL)-1 and -2 production were examined in 39 patients (32 consecutive; 7 previous) and 14 controls. Results in the FMF group indicated no change in total T-cells and B-cells. The number of supp T-cells and helper cells were significantly decreased, as compared to the controls (14 +/- 5.2, 19 +/- 4.6 vs. 31 +/- 4.6, 41 +/- 5.3, respectively), and the NK cells were significantly increased (16 +/- 4.8, 36 +/- 2.1). Peripheral blood monocytes from the patients with FMF produced higher amounts of IL-1 and lower amounts of IL-2 than those from the control subjects. The latter results were enhanced when the FMF group was subdivided on the basis of pretreatment with colchicine and presence of amyloidosis. This study, although preliminary, indicates an immune regulation imbalance in FMF patients. Further research is necessary to understand the interrelation of amyloidosis and colchicine treatment.

Adolescent↗

Serum immunoglobulin A levels and ethnicity in an Israeli population sample.

Serum IgA concentrations were measured in 1799 healthy Israeli military recruits (698 women and 1101 men) using an automated nephelometric system. The overall prevalence of IgA deficiency defined at a level of less than 50 mg/liter was 1.0 +/- 0.46% (95% confidence limits). No significant difference was found between the sexes in the mean values of serum IgA. Statistically significant ethnic differences were evident. Recruits of European origin had lower serum IgA concentrations than the North African, Israeli, or Asian origin groups. Whether the apparently high prevalence of IgA deficiency in this young population in Israel has clinical significance is at present unknown.

Africa, Northern↗

Abnormalities of cellular immunity and natural killer cells in Gaucher's disease.

Gaucher's disease (GD) which is a congenital defect characterized by the accumulation of glucocerebroside in cells of the reticulo endothelial system, is associated with malignancies of the lymphoid system such as multiple myeloma, chronic lymphatic leukemia, as well as acute leukemia of childhood. We report the immunological profile of the T-cell system in GD patients and in GD carriers. We found a variable response to lectins stimulation (PHA, Con A, PWM in various concentrations) which supports the hypothesis that a persistent antigenic stimulation in GD affects all components of the immune system of those patients. A highly significant decrease in the number of NK cells was also found, which might be a predisposing factor to the increase in malignant B and other lymphoid cell proliferations described in patients with GD.

B-Lymphocytes↗

Immunocompetence in pregnancy: production of interleukin-2 by peripheral blood lymphocytes.

Pregnancy is a natural allograft and the mechanisms for its non-rejection are obscure. Depression of maternal cellular immunity was suggested as a possible explanation. Interleukin-2(IL-2) is a lymphokine release from OKT4+ lymphocyte. This factor has a crucial role in the proliferation and differentiation of T cell subsets, and controls functions associated with immune rejection mechanisms. We therefore examined the ability of lymphocytes from women in the 3 trimesters of pregnancy to produce IL-2 in culture. Mononuclear cells were cultured with PHA for 48 h. The IL-2-containing supernatant was added to and supported the proliferation of an IL-2 dependent T cell line. Proliferation of this line indicated the IL-2 content of the added supernatant. Using this assay, IL-2 production in all 3 trimesters of pregnancy was adequate and comparable to that of lymphocytes from non-pregnant women. These results suggest that the proposed defect in cellular immunity during pregnancy is not mediated by an inability of the lymphocytes to produce IL-2.

Adult↗

Inhibition of lymphocyte response to mitogens by dipyridamole: preliminary findings.

It has been recently noted that dipyridamole (DP) may be involved in certain immunological reactions, in addition to its antiplatelet action. In the present investigation the mitogenic response of human lymphocytes from three groups of subjects to 3 different lectins was examined. In both the experimental group treated over a short period and in the controls a highly significant decrease in the mean lymphocyte response to all 3 mitogens was noted following 3 days of DP administration. The response remained low after an additional 3 days of treatment. Discontinuation of drug administration was followed by a significant increase in response to two mitogens, concanavalin A (Con A) and pokeweed mitogen (PWM). The response to phytohaemagglutinin (PHA) extent only increased to a small, non-significant. No change in the mean mitogenic response was detected in the group undergoing long-term treatment. The mechanism by which DP alters lymphocyte activity is as yet unknown.

Adult↗

Interleukin-2 production by cord blood lymphocytes stimulated with mitogen and in the mixed leukocyte culture.

We examined the ability of cord blood lymphocytes to produce interleukin-2 (T cell growth factor) in response to phytohemagglutinin and in the mixed leukocyte culture. Interleukin-2 production was measured by the proliferative response of an interleukin-2-dependent mouse T cell line to the addition of supernatant obtained from cord blood lymphocyte cultures. Using these assays we have shown that cord blood lymphocytes have a normal ability to produce interleukin-2 in both PHA-stimulated cultures and in the mixed leukocyte culture. The normal production of interleukin-2 by cord blood cells indicates, that newborn T lymphocytes are mature, and that a dissociation exists between their normal ability to produce interleukin-2 and their ability to produce other lymphokines, which was reported to be impaired. The reported deficiency of HLA-DR antigen expression on newborn monocytes does not seem to interfere with the production of interleukin-2 in the mixed leukocyte culture.

Fetal Blood↗

The immune system in isolated IgA deficiency.

The immune systems were compared in 23 subjects with isolated IgA deficiency and 15 controls with normal levels of IgA. The IgA deficient group had higher levels of serum IgM, and lower stimulation indices for the mitogens Con A, PWM and PHA; only the index for PHA was statistically significant. Their suppressor T-cell activity was decreased and chemotactic activity significantly decreased. They also exhibited a decrease in Leu 3, and a significantly lower ratio of Leu 3 to Leu 2. The mean percent of positive NBT neutrophils was decreased. An imbalance in the immunoregulatory mechanism is suggested as a possible explanation for IgA deficiency.

Adult↗

Interleukin-2 production and response to exogenous interleukin-2 in a patient with the acquired immune deficiency syndrome (AIDS).

The ability of lymphocytes from a patient suffering from the acquired immune deficiency syndrome (AIDS) to produce interleukin-2 (IL-2) was found to be comparable to that of his healthy sex partner and to that of a normal control. Addition of exogenous IL-2 to lymphocyte cultures did not improve the poor mitogen response to phytohaemagglutinin in this patient. Our data suggest that the underlying defect in this AIDS patient is due to an IL-2 receptor defect.

Acquired Immunodeficiency Syndrome↗

Campylobacter enteritis in normal and immunodeficient children.

Campylobacter fetus subspecies jejuni (CBJ) has been recently recognized as a common pathogen in bacterial gastroenteritis in children. During a period of 16 months, 51 cases of C fetus subspecies jejuni gastroenteritis were diagnosed. Five of the children in whom the cases were diagnosed were previously known to be immunodeficient: two had X-linked agammaglobulinemia, one had agammaglobulinemia, one had combined immunodeficiency, and one had transient hypogammaglobulinemia. Average duration of fever and diarrhea was longer in the five immunodeficient children (15 and 23 days, respectively) compared with the normal children (four and five days, respectively). Excretion of C fetus subspecies jejuni in stool persisted for 20 to 27 days in four of the immunodeficient children and for one year in the fifth, whereas normal children excreted C fetus subspecies jejuni for only four to 16 days. Campylobacter fetus subspecies jejuni may be added to the list of bacterial pathogens most likely to infect immunodeficient children, especially those with a defect of the humoral system.

Campylobacter Infections↗