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Biomedical subjects

R Lenkei

Publications and source records attributed to R Lenkei.

At least 37 records · Page 2Linked to original sources

Flow cytometry of blood and bone marrow cells from patients with hairy cell leukemia: phenotype of hairy cells and lymphocyte subsets after treatment with 2-chlorodeoxyadenosine.

By flow cytometry and an extensive set of markers, we characterized leukemic cells from the blood and bone marrow of 68 symptomatic patients with hairy cell leukemia (HCL). Hairy cells identified in the large cell gate always expressed CD19, CD20, HLA-DR, CD45RA, and B-ly 7. Other markers were occasionally expressed, such as CD38, CD45RO, CD23, CD15, CD4, CD5, and CD10 (expressed on more than 20% of the hairy cells in 44%, 25%, 21%, 18%, 12%, 10%, and 5% of evaluated cases, respectively). During treatment with 2-chlorodeoxyadenosine (CdA), the median lymphocyte counts decreased from 2,000/microL to 300/microL. Flow cytometry was repeated at the nadir (n = 24) of lymphocyte counts, at 3 months (n = 46), at 6 months (n = 50), at 1 year (n = 39), and at 2 years (n = 12) after treatment. The initial decrease of CD8+ and CD20+ cells was greater than that of CD4+ and natural killer (NK) cells, leading to an increasing CD4/CD8 ratio. Median nadir values of CD4+, CD8+, CD20+, and NK cells were 128/microL, 78/microL, 10/microL, and 13/microL, respectively. The subsequent recovery was quicker for CD8+ and NK cells, leading to a normalization within 3 months, whereas CD20+ and CD4+ cells required 1 or 2 years to enter the normal range. The CD4/CD8 ratio thus decreased after the nadir and remained less than 1. CD45RA+ CD4 cells and CD45RA+/CD45RO+ double-positive cells were less affected by CdA. Activated T cells, ie, HLA-DR+ cells, rarely decreased below the normal range and often recovered with an overshoot. CD10+ cells increased in the bone marrow posttreatment as an indication of normal B-cell regeneration in 16 of 36 (44%) patients. The quick regeneration of certain lymphoid subsets might explain the lack of late infections in CdA-treated HCL patients.

Adult↗

Serum levels of lymphokines and soluble cellular receptors in primary Epstein-Barr virus infection and in patients with chronic fatigue syndrome.

The immunopathology in primary Epstein-Barr virus (EBV) infections and in chronic fatigue syndrome was studied by examining serum levels of interleukins (IL) and of soluble T cell receptors in serum samples. Serum samples were from patients during and 6 months after primary EBV-induced infectious mononucleosis and from patients with chronic fatigue syndrome and serologic evidence of EBV reactivation. Markers for T lymphocyte activation (soluble IL-2 and CD8) and for monocyte activation (neopterin) were significantly elevated during acute infectious mononucleosis but not in patients with chronic fatigue syndrome. Interferon-alpha, IL-1 beta, and IL-6 levels were not significantly increased in any patient group but inferferon-gamma levels were significantly increased during the acute phase of infectious mononucleosis. The levels of IL-1 alpha were significantly higher than in controls both in patients with infectious mononucleosis and in those with chronic fatigue syndrome. In the latter, the lack of most markers for lymphocyte activation found in patients with infectious mononucleosis makes it less likely that EBV reactivation causes symptoms.

Adolescent↗

Peripheral blood lymphocyte subsets in patients with chronic hepatitis C--effects of interferon treatment.

Thirty-three patients with chronic hepatitis non-A, non-B/C were included in a randomized controlled study of recombinant alpha-2b interferon treatment 3 MU three times weekly for 36 weeks. In lysed whole blood, lymphocyte subpopulations were enumerated by flow cytometry detecting fluorescein or phycoerytrin conjugated monoclonal antibodies directed against seven different epitopes. Patients with chronic active hepatitis were significantly older than patients with chronic persistent hepatitis (p less than 0.05). Before treatment, the proportions of different subsets of lymphocytes were within the normal reference values and the CD4/CD8 ratio was also normal. No increased activation of T-cells was noticed. Patients over 50 years of age, however, had a significantly increased (p less than 0.01) proportion of HLA-DR+ lymphocytes, mainly B-cells. Treatment decreased the absolute number of peripheral blood leukocytes and lymphocytes. There was also a significant decline in the proportion of CD8+ lymphocytes and NK-cells, and a significant increase in the proportion HLA-DR+ cells and of the CD4/CD8 ratio. The increased proportion of HLA-DR+ cells, however, did not reflect peripheral T-cell activation; instead, it was due to increasing B lymphocyte numbers.

Alanine Transaminase↗

Expression of CD15 as predictor of relapse in children with acute lymphoblastic leukemia of the pre-B type.

Pre-B acute lymphoblastic leukemia (ALL) was diagnosed in 37 children morphologically, histochemically, and by immunophenotyping by flow cytometry. In all patients the leukemic blasts expressed HLA-DR and CD19 (Leu-12). In 10 patients 20% or more of the blast cells expressed a myeloid antigen: CD15 (Leu-M1) in seven, CD33 (My9) in two and CD13 (My7) in one patient. All 37 children achieved complete remission, but eight relapsed. Relapse occurred in six of seven patients with CD15-positive blasts, but in only two of 27 patients with CD15-negative blasts (p = 0.0003). Thus, the occurrence of CD15 on the blasts of children with pre-B ALL shows a remarkable association with a high risk of relapse, and these patients should therefore be considered to belong to the high-risk group regardless of other prognostic factors.

Adolescent↗

Persistent productive HIV infection in EBV-transformed B lymphocytes.

The susceptibility to HIV infection of 14 B-cell lines established from five healthy HIV seronegative and from six HIV seropositive subjects by lymphocyte transformation with EBV and/or by lymphocyte cultivation with cyclosporin A was studied. Although the cell lines contained different proportions of CD4-positive cells, as shown by flow cytometry, all of them could be infected with the SF-2 strain of HIV. Infection was blocked by a monoclonal antibody directed against the viral attachment site of the CD4 molecule, even in a line that lacked demonstrable CD4 receptors. B-cell lines with high proportions of CD4-expressing cells produced HIV p24 antigen more rapidly and at higher concentrations than cell lines with low CD4 expression. Although HIV infection resulted in some cytopathic effects, it was possible to cultivate the infected cells for more than 8 months without refeeding the cultures with uninfected cells. Even in long-term cultures, there was a continuous production of infectious HIV, as detected by transfer of culture supernatants to other susceptible cell lines. The production of viral antigens was consistently more pronounced in the B-cell line with the highest CD4 positivity than it was in a permissive T-cell line (HUT-78) infected in the same manner. These results indicate that HIV can chronically and productively infect transformed B cells via interaction with CD4 molecules. Thus it is possible that B cells may constitute a source of infectious virus in HIV-infected EBV-positive individuals.

Antigens, Differentiation, T-Lymphocyte↗

Correlation between cytomegalovirus and toxoplasma gondii serology and lymphocyte phenotypes in peripheral blood and cord blood.

Increased numbers of peripheral blood HNK1+ lymphocytes have been reported in transplant recipients, hemophilia patients treated with clotting factor concentrates, and HIV carriers. Our previous work has revealed a significant effect of cytomegalovirus (CMV) carrier status on HNK1+ lymphocytes. Since other antigenic stimuli may be also involved, we compared the effects of Toxoplasma gondii and CMV carrier status on lymphocyte subsets as defined by the CD3 and HNK1 markers in 288 healthy individuals. In contrast to CMV, T gondii carrier status had no significant effects on the CD3+, HNK1+ and CD3-, HNK1+ lymphocyte subsets. That result may be explained by the different relationships between these 2 microorganisms and their hosts. We also studied the effect of maternal CMV carrier status on the HNK1 expression by their offsprings' cord blood lymphocytes. None of the 100 newborns studied had serological evidence of congenital CMV infection. There were only few HNK1+ lymphocytes in the cord bloods, of which the majority was CD3-, and their proportions were not significantly influenced by maternal CMV carrier status. Since there has been probably no direct contact between maternal CMV and the newborns' immune systems, we suggest that the effect of CMV on the HNK1+ lymphocytes of its carriers, results from a direct interaction between virus or virus-infected cells and the immune system.

Adolescent↗

B-cell chronic lymphocytic leukaemia with aberrant expression of CD8 antigen.

The monoclonal antibodies against CD8 (T suppressor/cytotoxic) antigen (Leu2/OKT8) were found to bind to leukaemic lymphocytes from a patient with chronic lymphocytic leukaemia. The cells also had an unusual type of rod-like cytoplasmic immunoglobulin of IgM/lambda type as seen by light, fluorescence and electron microscopy, and displayed several antigens characteristic for B lymphocytes. Gene rearrangement analysis showed rearrangement of mu heavy chain gene. In spite of an expression of CD8 antigen, T-cell receptor genes were not rearranged.

Aged↗

Interleukin-2 can induce proliferation of leukemic B-cells in prolymphocytic leukemia.

In a case of prolymphocytic leukemia (PLL), receptors for interleukin-2 (IL-2R) were demonstrated by immunofluorescence with a monoclonal antibody against IL-2R. Highly purified leukemic B-cells, cultured in vitro with recombinant IL-2 (r-IL-2), responded to IL-2 with a marked increase of DNA-synthesis. Both spontaneous and r-IL-2-induced proliferation of leukemic cells were totally abrogated by the anti-IL-2R monoclonal antibody.

Aged↗

Malignant B-cells have receptors for and respond to interleukin-2.

Interleukin-2 (IL-2) for a long time has been considered as a T-cell specific growth factor which acts through distinct surface receptors present on activated, but not on resting, T-lymphocytes. Recently it has been shown that activated murine and human B-cells also express IL-2 receptors and respond to IL-2 with an increase of DNA synthesis. Some human B-cell malignancies have been reported to react with anti-IL-2 receptor antibodies, but no response to IL-2 has been documented in these cases. Here, in five of 11 B-cell leukemia/lymphoma cases, we identified cells which not only express the IL-2 receptor, but also respond to IL-2 stimulation, as shown by a marked increase of 3H-thymidine incorporation and by differentiation of lymphoma cells. The IL-2-induced 3H-thymidine uptake was completely blocked by a monoclonal antibody to IL-2 receptor, which indicates that IL-2 acted directly through functional IL-2 receptors.

Antibodies, Monoclonal↗

Autoantibodies to the basal cells of squamous epithelium react with thymic epithelial cells.

Sera from carriers of hepatitis B surface antigen (17 out of 21), which reacted in immunofluorescence with the basal cell layer (BCL) of squamous epithelium, were also shown to react with a thymic stellate epithelial cell (SEC) characterized by long, dendritic-like cytoplasmic processes. Absorption of the autoantibodies against BCL of squamous epithelium (BCL-Ab) with a thymic homogenate abolished the reactivity with BCL and SEC, demonstrating that the same antigenic determinant was recognized in both cells. In the human thymus, SEC were present both in the cortex and in the medulla. In the outer cortex SEC delineated the septal spaces. SEC were also stained by anti-HLA-DR (Ia) but not by antiactin monoclonal antibodies. The morphology and distribution of SEC were similar to those of the previously described thymic epithelial cells containing alpha-1 thymosin (K. Hirokawa, J. E. McClure, and A. L. Goldstein, Thymus 4, 19, 1982). BCL-Ab were also found to react with five human epithelial thymomas. BCL-Ab seemed to be useful for further characterization of the thymic epithelial cells and for the immunodiagnosis of thymoma.

Actins↗

Reactivity of sera from patients with liver disease with glutaraldehyde-treated erythrocytes: role for false positive results in hemagglutination tests.

The use of glutaraldehyde as a coupling reagent in the passive hemagglutination test (HA) has gained wide application, especially for the coating of red blood cells (RBC) with glutaraldehyde-polymerized human serum albumin (pHSA), for studies of the albumin receptor on hepatitis B surface antigen (HBsAg) or for the detection of anti-albumin antibodies (AAA). Here we report a previously unrecognized reactivity with glutaraldehyde-treated RBC mainly with sera from patients with liver disease. The highest incidences of this reaction were found in patients with acute viral hepatitis A and B, namely 44 of 50 (88%) and 31 of 50 (62%) respectively. In 234 HBsAg carriers the frequency was low (3%). This reactivity was also observed in 19 of 50 sera from patients with chronic liver disease documented by biopsy, but not in sera from 68 healthy subjects. By immunofluorescence on glutaraldehyde-treated RBC it was shown that the corresponding antibodies belonged mainly to the IgM class. In all HBsAg-negative patients studied the HA titer against glutaraldehyde-treated RBC was in agreement with the titer against RBC coated with pHSA or pBSA (polymerized bovine serum albumin). Absorption with pHSA abolished the reaction with glutaraldehyde-treated RBC in 7 of 8 sera, suggesting a common reactivity between glutaraldehyde-polymerized HSA and glutaraldehyde-treated RBC. Apart from the possible clinical importance of these antibodies, their existence is a possible source of false positive results when glutaraldehyde is used as a coupling reagent for immunological assays, in particular with sera from patients with liver diseases.

Actins↗

Autoantibodies against the basal cell layer: an association with chronic hepatitis B.

The presence of antibodies against the basal cells of squamous epithelium (BCL-Ab) was studied by indirect immunofluorescence in Rumanian and Swedish carriers of hepatitis B surface antigen (HBsAg), in patients with acute viral hepatitis (AVH), chronic liver diseases (CLD), and various other diseases, and in apparently healthy subjects. Titers of BCL-Ab greater than or equal to 40 were found in 8% of 320 HBsAg carriers, in 20% of 292 patients with CLD associated with HBsAg, and in 2% of 816 patients with HBsAg-negative CLD. BCL-Ab were not found in 167 patients with AVH, nor in 1389 patients with various nonhepatic conditions, nor in 344 apparently healthy subjects. These data indicate an association of BCL-Ab with CLD predominantly of hepatitis B etiology. Possibly hepatitis B virus may induce a form of liver metaplasia with the expression of an antigen with a specificity in common with the regenerative layer of basal cells in the squamous epithelium.

Autoantibodies↗

An immunological hypothesis for plasma protein catabolism.

A selective mechanism of plasma protein catabolism is suggested, based on three main assumptions: (1) plasma proteins are submitted to molecular ageing thus achieving "modified" forms after a given time period; (2) the system recognizing the "modified" molecules consists of preformed physiological autoantibodies; (3) the elimination of the immune complexes formed between "modified" proteins and the corresponding autoantibodies takes place via binding to Fc receptor bearing cells.

Animals↗