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Biomedical subjects

S Peller

Publications and source records attributed to S Peller.

At least 19 recordsLinked to original sources

Decreased CD45RA T cells in B-cell chronic lymphatic leukemia patients: correlation with disease stage.

T-cell subsets CD4, CD8 and suppressor-inducers (CD45RA) were determined in 20 patients with B-cell chronic lymphatic leukemia (B-CLL). The proportion of CD4 and CD45RA was decreased when compared with T cells from normal subjects. CD8 was markedly increased. The activity of concanavalin A-induced suppressor cells was not significantly different from that of normal controls and was negatively correlated to the percentage of CD4 of B-CLL patients. The selective loss of CD45RA cells was more prominent in patients in advanced Rai stages of the disease (III to IV) than in early stages (0 to II). Six patients of the advanced stages group suffered from autoimmune hemolytic anemia, whereas no patient in the early stages of disease showed an autoimmune phenomenon. Our results may indicate a mechanism of autoimmunity in B-CLL similar to that of patients with autoimmune diseases.

Aged

Tuftsin induces tissue factor-like activity in human mononuclear cells and in monocytic cell lines.

Normal human monocytes and macrophages generate potent procoagulant activity (PCA) resembling tissue factor (TF) in response to various stimuli. In this study we show that tuftsin, a natural stimulator of many functions of monocytes and macrophages, also stimulates a potent PCA in mixed mononuclear cells and monocytes, and a mild PCA in lymphocytes and cell lines of monocytic origin (U937 and THP). No activity was generated by several lymphoid cell lines and HL-60 cells. The PCA resembled TF in that it accelerated clotting through the extrinsic coagulation pathway and was inhibited by concanavalin-A and by monoclonal anti-TF antibodies. The induction of TF-like activity by tuftsin was dose- and time-dependent. It was located in the cell membrane and did not require T cells for expression. Generation of TF-like activity was prevented by actinomycin D, while cytarabine had no effect on this process, suggesting that expression of the activity depends on protein synthesis. Studies with various tuftsin analogs suggest that tuftsin stimulates generation of TF-like activity, as well as other functions of monocytes via the same receptors. The results with the monocytic cell lines show that tuftsin affects mainly mature cells. The induction of TF-like activity in mononuclear cells by tuftsin constitutes an important link between mononuclear cells and the immune and coagulation systems. It may play a major role in the pathogenesis of thromboembolism and fibrin deposition in various inflammatory and immunologic disorders.

Blood Coagulation Factors

Rearrangements in the p53 gene in Philadelphia chromosome positive chronic myelogenous leukemia.

Molecular structural analysis of the p53 gene in patients with Philadelphia chromosome-positive chronic myelogenous leukemia (CML) indicates a significant incidence of gene rearrangements in patients at either accelerated phase or blastic crisis. Southern blot analysis of genomic DNA hybridizing with either genomic or cDNA p53 specific probes indicated that 30% of the CML patients at blastic crisis phase exhibited rearrangements, mostly mapping downstream to the first non-coding exon. This is compatible with the observation that the progression of CML from the chronic to the acute phase involves frequent aberrations in chromosome 17, to which the p53 oncogene has been mapped. Therefore, we suggest that one of the pathways of development of CML to the acute phase is associated with aberrations in the p53 nuclear oncogene.

Blast Crisis

Common variable immunodeficiency: a family study and therapeutic trial with cimetidine.

Various immunologic parameters were tested in a family of two patients with common variable immunodeficiency. Both patients had low serum immunoglobulin levels, low peripheral B cell and T4 subclass of lymphocytes, and reversed T4/T8 ratio. One of the patients had excessive suppressor activity. Two of the asymptomatic members of the family (the father and one brother) had also low T4/T8 ratio that was not associated with excessive suppressor activity. No linkage between the disease inheritance to HLA could be observed. A study of the T cell helper activity to an antigen, the response to which is regulated by an HLA-linked gene, suggested a defect in the immune response of the two patients and their asymptomatic brother with immunologic disorders. Treatment with cimetidine of the patient with excessive suppressor activity led to an improvement in his clinical state, reduction in suppressor activity, temporary effect on his proliferative response capacity to mitogens, and an increase in the antigen-specific helper activity.

Adult

Increased concanavalin A-induced suppressor cell activity in humans with occupational lead exposure.

E-rosette-forming cells (E-RFC), mitogen-induced blast transformation, OKT4+, OKT8+ cells, and their ratio were found to be normal in 10 subjects chronically exposed to lead with blood levels of 40-51 micrograms%. However, concanavalin A (Con A)-induced suppressor cell activity (SCA) in these subjects was significantly greater than in normal matched controls. The clinical relevance of this observation is not clear, but it may have some bearing on the various immunologic defects described in lead exposure.

Adult

Effect of levamisole on chemotaxis of granulocytes from uremic patients.

Uremic granulocyte chemotaxis was assessed in the presence of four different concentrations of levamisole. Chemotactic responsiveness of uremic granulocytes was significantly decreased compared to normal, both in the absence of levamisole and with all levamisole concentrations tested. However, with 10(-3) and 10(-4) M levamisole concentrations, uremic granulocyte chemotaxis was similar to that of normal granulocytes without levamisole. Defective chemotactic activity of granulocytes may play a role in the increased susceptibility of uremic patients to infections. Pharmacological correction of this defect may improve the patients' ability to cope with infections.

Adult

1,25-Dihydroxyvitamin D-induced suppressor cells in uremic versus normal lymphocytes.

1,25-Dihydroxyvitamin D3 (DHD) has been shown to suppress mitogen-induced blast transformation. This inhibition is abolished by prior elimination of adherent cells. Chronic renal failure is an immunodeficiency state on the one hand and is associated with abnormalities in vitamin D metabolism on the other. The effect of DHD on the induction of suppressor cells in uremic vs. normal peripheral blood mononuclear cells was investigated. Study groups included 16 chronically uremic patients and 16 age- and sex-matched controls. DHD induced suppressor cell activity in normal lymphocytes. However, no suppressor cell activity was observed in lymphocytes from the uremic patients preincubated with DHD. The origin of the responder cells (normal or uremic) did not affect the outcome. The results would suggest that monocyte-adherent suppressor cells from uremic subjects are either incapable of binding DHD or fail to mount a normal post-receptor intracellular chain of events culminating in suppressor activity.

Adult

Induction of suppressor cells in normal lymphocytes by uremic serum.

Sera of patients on chronic hemodialysis induced suppressor cell activity (SCA) in normal peripheral blood mononuclear cells, which significantly impaired blastogenic response to PHA. This SCA is statistically not different from Con A induced SCA. Both SCAs are however additive. Speculations concerning the modes of action of this induced SCA are discussed.

Adult

Immunoregulatory defect in patients with autoimmune thrombocytopenic purpura (ATP).

Con A-induced suppressor cells were studied in 20 patients with autoimmune thrombocytopenic purpura and 20 normal controls. Percentage of suppression was determined on autologous and allogenic lymphocytes during blast transformation with phytohemagglutinin (PHA). In 10 patients and 10 controls helper (T4) and suppressor (T8) subsets were also determined, using monoclonal antibodies. We found a significant decrease in patients' suppressor cell activity both with autologous and allogeneic lymphocytes. Patients' responder lymphocytes were also impaired when tested with normal suppressor cells. The numbers of T4 and T8 in patients was found to be normal although the ratio T4/T8 was somewhat lower than in normal controls. There was a significant direct correlation between the numbers of T4 of patients and their suppressor cell activity on allogeneic lymphocytes suggesting an immunoregulatory defect at the level of induction of suppressor cells.

Adolescent

The effects of uremic serum and 3'-5' cyclic AMP on blastogenesis of normal lymphocytes.

Phytohemagglutinin (PHA) induced lymphocyte blast transformation is impaired both in uremic lymphocytes and in normal lymphocytes exposed to uremic serum. Cyclic AMP is known to inhibit blast transformation in normal and uremic lymphocytes. This investigation was undertaken to assess quantitatively the effects of uremic serum and cyclic AMP on blastogenesis of normal lymphocytes. Uremic serum or cyclic AMP significantly inhibited blast transformation of normal lymphocytes. These effects were statistically similar and cumulative. We conclude that the inhibition imposed by uremic serum on normal lymphocyte blastogenesis is predominantly mediated by a mechanism(s) different from cyclic AMP.

Cells, Cultured

The effect of several uremic parameters on uremic serum inhibition of lymphocyte blastogenesis.

Uremic sera are known to inhibit thymidine incorporation of normal lymphocytes. The nature of the factor(s) responsible for this inhibitory effect has not been completely elucidated. In this study a possible correlation was investigated between a number of uremic blood constituents altered with the progression of the disease and the immunoinhibitory effect of the respective sera. No such correlation was found with the values of hematocrit, urea, creatinine, calcium and phosphorus. On the other hand a significant negative correlation emerged between H+ and Mg2+ ion levels and the inhibition imposed on normal lymphocyte thymidine incorporation. This apparently paradoxical result would indicate that with regard to these two parameters the greater the severity of renal failure the smaller would be the immunoinhibitory effect of the respective serum. The inhibition imposed by uremic serum on immune functions is probably a multifactorial phenomenon, in which H+ and Mg2+ might play a role antagonistic to inhibitory factors.

Adult

Functions of polymorphonuclear (PMN) leukocytes of patients with lymphoproliferative diseases.

PMN leukocytes from untreated patients with multiple myeloma (MM), Hodgkin's disease (HD) and non-Hodgkin lymphoma (NHL) were studied in vitro for their phagocytic and chemotactic function. Alkaline phosphatase score and the reduction of nitroblue tetrazolium (NBT) in these leukocytes were also determined. Most of the functions of PMN leukocytes from untreated patients with MM were impaired, compared to control leukocytes, while those from patients with HD and NHL were impaired only in their chemotactic response to casein and endotoxin-activated serum (EAS).

Adolescent

UV-endonuclease from calf thymus with specificity toward pyrimidine dimers in DNA.

We describe the partial purification of an endonuclease from calf thymus that nicks phage PM2 DNA irradiated with UV doses producing only a few pyrimidine dimers per molecule. It has much less activity on DNA that has been subjected to enzymatic photoreactivation after UV irradiation. The calf thymus endonuclease is different from other mammalian UV-endonucleases so far described in that it seems to be dimer specific. The enzyme is stimulated by Mg2+ and is inactive in the presence of EDTA. It binds to UV-irradiated DNA-Sepharose from which it is released by low concentrations of KCl. Gel filtration data indicate that the endonuclease may belong to a high molecular weight protein or protein complex. The enzyme is very labile and freezing increases its lability.

Animals