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Biomedical subjects

R J Levinsky

Publications and source records attributed to R J Levinsky.

At least 91 records · Page 5Linked to original sources
PubMed1989

Mechanisms of lymphocyte adhesion to endothelial cells: studies using a LFA-1-deficient cell line.

In order to investigate the role of lymphocyte function-associated antigen 1 (LFA-1) in lymphocyte adhesion to endothelial cells (EC), we have studied the adhesion of a LFA-1-deficient lymphoblastoid cell line, ICH-KM, which has < 10% of the cell surface LFA-1 expressed on a normal lymphoblastoid cell line, ICH-BJ. The adhesion of ICH-KM cells to unstimulated EC was 49.9 +/- 8.6% (mean +/- SD) that of ICH-BJ cells. Moreover, phorbol ester-stimulated ICH-KM cells showed a considerably weaker increase in adhesion to unstimulated EC compared with ICH-BJ cells (mean +/- SD increase in percentage adhesion, 3.8 +/- 2.3 compared with 18.5 +/- 8.0; P<0.025). In contrast, there was no significant difference between the enhanced adhesion of ICH-KM cells and ICH-BJ cells to interleukin-1 (IL-1)-stimulated EC. Thus ICH-KM cells showed a 22.7 +/- 11.0 (mean +/- SD) increase in percentage adhesion to IL-1-stimulated EC compared with the 24.8 +/- 8.5 increase in percentage adhesion of ICH-BJ cells. Anti-LFA-1 monoclonal antibodies had no effect on the enhanced adhesion of ICH-KM and ICH-BJ cells to IL-1-stimulated EC but abolished the differences in adhesion between the two cell lines. The study therefore indicates that although a major part of unstimulated and phorbol ester-stimulated lymphocyte-EC adhesion is dependent upon LFA-1, the enhanced adhesion due to stimulation of EC with IL-1 is not dependent upon this molecule. The data therefore supports the existence of cytokine-inducible LFA-1-independent adhesion molecules for lymphocytes on EC.

Antibodies, Monoclonal↗
PubMed1989

Epstein-Barr-virus-transformed lymphoblastoid cell lines derived from patients with X-linked agammaglobulinaemia and Wiskott-Aldrich syndrome: responses to B cell growth and differentiation factors.

Epstein-Barr-virus-transformed B lymphoblastoid cell lines (EBV-transformed LCL) from three patients with X-linked agammaglobulinaemia (XLA), six patients with Wiskott-Aldrich Syndrome (WAS), and seven normal donors, were tested for growth and differentiation in response to human recombinant IL-4, a commercially available, low molecular weight B cell growth factor (BCGFlow), and B cell differentiation factor (BCDF) secreted by the T24 cell line, now known to be IL-6. Proliferation (3H-TdR uptake) by EBV-transformed LCL from both XLA and WAS patients in response to BCGFlow was similar to that obtained with the normal cell lines. In addition, three normal and three WAS, but none of the XLA EBV-transformed LCL, proliferated a little in response to IL-4. All the normal B cell lines secreted IgM, and six out of the seven secreted IgG in response to BCGFlow and BCDF. A similar pattern of response was obtained with the WAS EBV-transformed LCL (6/6 secreted IgM and 4/6 secreted IgG). Several of the normal and WAS EBV-transformed LCL also secreted IgM and IgG in response to IL-4. In contrast, the lines from the XLA patients were abnormal. One secreted large amounts of IgM and two secreted small amounts, but none of the XLA lines secreted IgG constitutively or in response to any of the factors (IL-4, BCDF). The lack of detectable IgG secretion by the XLA lines was probably due to an absence of precommitted IgG B cell precursors transformed by EBV rather than an intrinsic inability to respond to BCGF and BCDF. All of the lines, including those derived from XLA patients, were shown to secrete B cell growth and differentiation factors detected on indicator B cell lines. These results suggest that the abnormal X-linked genes responsible for XLA and WAS do not interfere with B cell responses to B cell growth and differentiation factors.

Agammaglobulinemia↗
PubMed1989

Role of the LFA-1 adhesion glycoprotein in neutrophil adhesion to endothelium and plastic surfaces.

Neutrophil adherence to endothelium is known to be mediated, at least in part, by adhesion molecules such as LFA-1. Deficiency of these adhesion molecules leads to recurrent infection and early death from infection. As screening for defects of these adhesion glycoproteins is often performed by the ability of neutrophils to adhere to plastic plates, in this study a comparison of neutrophil adherence by the CD18/CD11a (LFA-1) mechanism to endothelium and plastic surfaces was examined. Baseline neutrophil adherence was two-fold higher to plastic than to endothelium (17% +/- 9 for plastic, 8% +/- 5 for endothelium). Baseline adherence to endothelium was partially inhibitable by anti-LFA-1 antibodies, whereas no inhibition of adherence occurred on plastic. Neutrophil stimulants increased adherence to both surfaces, although only on endothelium was this increase attributable to the LFA-1 mechanism. IL-1 increased adherence to endothelium, but had no effect on plastic. We conclude that adherence of neutrophils to plastic surfaces probably represents overall activation status through undefined mechanisms, is not by LFA-1 receptor ligand interactions, and is therefore a non-physiological phenomenon. Endothelial receptors are pivotal in neutrophil adherence. It would be more appropriate to screen leucocytes for leucocyte adhesion deficiency by assaying for specific receptor occupancy with monoclonal antibodies, rather than an assay such as adhesion to plastic where the adhesion ligand is non specific.

Antigens, Differentiation↗
PubMed1988

Use of X chromosome inactivation analysis to establish carrier status for X-linked severe combined immunodeficiency.

Analysis of X chromosome inactivation in T-lymphocyte DNA from two obligate carriers of X-linked severe combined immunodeficiency showed a non-random pattern. This method was then used to establish carrier status in at-risk females in X-linked pedigrees. It was further used to differentiate between X-linked and autosomal recessive inheritance of the disease when the mode of inheritance was not clear from the pedigree. In addition, a mother of a boy affected by the sporadic form of the disease was found to have non-random X inactivation in her T lymphocytes and she is therefore a carrier of the X-linked disease.

Chromosome Mapping↗
PubMed1988

Genetic prediction in X-linked agammaglobulinaemia.

S21 (DXS17) and pXG12 (DXS94), two probes linked to the locus of X-linked agammaglobulinaemia (XLA), were used for genetic prediction in 13 such families. A method of allowing for nonallelic genetic heterogeneity was demonstrated in the calculation of the genetic risks, specifying a certain proportion of unlinked families. We further estimated the impact due to the uncertainty of the proportion of unlinked families on the final genetic risks in each family and this can be taken into account during genetic counselling.

Agammaglobulinemia↗
PubMed1988

Response of LFA-1-deficient B cells to interleukin 4 (BSF-1) and low molecular weight B cell growth factor (BCGFlow).

T cell-depleted B cells from a patient with LFA-1 deficiency were tested in costimulation assays for responsiveness to recombinant human IL4 (BSF-1) and purified low molecular weight B cell growth factor (BCGFlow). In both cases the response of LFA-1-deficient B cells was comparable with normal controls. Monoclonal antibodies to LFA-1 alpha (CD11a) and beta (CD18) chains were unable to mimic the action of IL4 on normal B cells in costimulation assays with anti-IgM, and did not inhibit normal B cell proliferation in response to IL4 and anti-IgM. Epstein-Barr virus-transformed lymphoblastoid B cell lines (LCL) from normal and LFA-1-deficient donors both responded in proliferation assays to BCGFlow but not IL4. Similarly, both normal and LFA-1-deficient LCL increased IgM secretion in response to BCDF, BCGFlow and, interestingly, IL4. The normal LCL also increased IgG secretion in response to these factors, but no IgG was detected in supernatants from the LFA-1-deficient LCL. These results show that LFA-1 expression is not essential for B cell responses to B cell growth and differentiation factors.

Antibodies, Monoclonal↗
PubMed1988

Natural and artificial immunity to varicella zoster virus.

The live varicella vaccine has been recommended for use in immunocompromised subjects and in adults who are susceptible to chickenpox. However, we do not know how humoral and cell-mediated immune responses induced after vaccination differed from those obtained after natural infection. To answer this, 45 previously infected subjects (23 chickenpox, 22 vaccinated) were tested for their varicella zoster virus (VZV)-specific antibody levels and for their lymphocyte stimulation responses to VZV antigen. Antibody was measured by both an enzyme-linked immunosorbent assay (ELISA) and an immunofluorescence assay (IF), while lymphocyte stimulation was detected by tritiated thymidine incorporation. Antibody was tested in ten postchickenpox and nine vaccinated subjects. About 6 to 8 weeks after first exposure, the magnitude of the responses determined by both ELISA and IFT were much higher in the naturally infected than in the vaccinated group (P less than 0.001) with both test methods). There was no significant difference in the lymphocyte transformation responses in both groups of subjects. Thirteen postchickenpox and 13 vaccinated subjects who had been infected at least 12 months previously were also tested. Total antibody levels were again significantly higher in the naturally infected than in the vaccinated group (P less than 0.001). One vaccinated subject had VZV-specific IgA and IgM in the serum. The magnitude of the lymphocyte transformation reaction was higher in the naturally infected than in the vaccinated group (P less than 0.01). Thus, antibody responses to VZV were better in naturally infected than in vaccinated subjects. The IFT appears to be a more sensitive technique for antibody detection in the vaccinated subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Viral↗
PubMed1988

Immunity to varicella zoster virus in children with leukaemia.

A total of 46% (32/70) of children with acute lymphoblastic leukaemia presenting to the Hospital for Sick Children had a past history of chickenpox. When their immunity to varicella zoster virus (VZV) was assessed, 75% (24/32) had a positive lymphocyte transformation response to VZV antigen in tissue culture while 78% (25/32) possessed IgG antibody against VZV. Therefore, at least 22% of the children were probably susceptible to infection with VZV inspite of having a history suggestive of chickenpox. Of those with a negative or uncertain history 34% had a positive lymphocyte transformation response, while 55% (21/38) had IgG antibody against VZV. Therefore, about one in two of those with a negative history to VZV had some form of immunity to VZV. Hence, regardless of their VZV infection history, children with leukaemia would need to undergo both cell mediated and humoral immunity tests before they may be considered for immunisation with the live varicella vaccine. From our studies, 34% (24/70) of our patients did not have any evidence of immunity to VZV by either test method. These would be considered for immunisation with the live varicella vaccine.

Adolescent↗
PubMed1988

Syndrome of erythroderma, failure to thrive, and diarrhea in infancy: a manifestation of immunodeficiency.

Five infants with a triad of symptoms comprising generalized erythroderma, failure to thrive, and diarrhea are presented. All of these children demonstrated significant immunologic abnormalities. This is a recognizable clinical syndrome that reflects immunodeficiency; however, the responsible immunodeficiencies do not appear to be the same in every case. Early investigation and appropriate therapy may considerably reduce morbidity, and mortality in children with this syndrome.

Child, Preschool↗
PubMed1988

Intestinal hypersensitivity reactions in the rat. I. Uptake of intact protein, permeability to sugars and their correlation with mucosal mast-cell activation.

We have confirmed previous observations that intestinal anaphylaxis induced in rats previously sensitized to ovalbumin (OVA) is associated with an increased uptake of an unrelated 'bystander' protein, bovine serum albumin (BSA) fed 1 hr previously. In this study, this enhanced protein uptake was associated with an increased lactulose/rhamnose excretion ratio after administration of these sugars, although there was no correlation between the two measurements. One hour after antigen challenge the serum levels of rat mast-cell protease II (RMCPII), a specific marker for mucosal mast-cell secretion, were significantly higher than both the pre-challenge levels and those of sham-challenged controls (P less than 0.002). There was a significant positive correlation between the serum levels of RMCPII and the lactulose/rhamnose excretion ratios (P less than 0.05), but no such correlation existed between RMCPII and BSA levels in the challenged rats. In other studies the urinary lactulose/rhamnose ratios of rats with cetrimide-induced gut damage were found to be significantly increased, although BSA uptake into the serum remained unaltered. We conclude that there is no simple correlation between gut permeation of low-molecular weight sugars and and the uptake of macromolecular proteins.

Animals↗
PubMed1987

The response of selected human B cell lines to B cell growth and differentiation factors.

Fifteen human B cell lines were tested for their ability to respond to B cell growth and differentiation factors present in phytohemagglutinin-conditioned medium. Five lines responded significantly: CESS showed an increase in IgG production only, HFB1 and BALM1 showed an increase in proliferation only and L4 and BALM4 showed an increase in both IgG production and proliferation. When four of the responding lines (CESS, HFB1, L4 and BALM4) were cultured with human recombinant-derived interleukin 1, interleukin 2, interleukin 4 or interferon-gamma no significant response was seen. CESS, L4 and BALM4 all increased IgG production in response to partially purified B cell growth factor (Cellular Products, Inc., Sera-Lab., Crawley Down, GB) and B cell differentiation factor-containing supernatant from the T24 bladder carcinoma cell line. HFB1, L4 and BALM4 all showed increased tritiated thymidine incorporation in response to purified B cell growth factor but not in response to B cell differentiation factor-containing supernatant. These lines may prove useful in the study of B cell growth and differentiation factors and their receptors.

B-Lymphocytes↗
PubMed1987

First trimester diagnosis of adenosine deaminase deficiency.

Adenosine deaminase deficiency has been detected in the first trimester by direct analysis of enzyme activity in chorionic villi in a pregnancy at risk. Data for purine nucleoside phosphorylase activity in chorionic villi from healthy controls in the first trimester are also presented and should allow equally rapid diagnosis of this disorder.

Adenosine Deaminase↗
PubMed1987

Close linkage of the locus for X chromosome-linked severe combined immunodeficiency to polymorphic DNA markers in Xq11-q13.

The gene for X chromosome-linked severe combined immunodeficiency (SCID), a disease characterized by a block in early T-cell differentiation, has been mapped to the region Xq11-q13 by linkage analysis with restriction fragment length polymorphisms. High logarithm of odds (lod) scores were obtained with the marker 19.2 (DXS3) (z = 5.51 at a recombination fraction theta = 0.11) and with the marker cpX73 (DXS159) that showed complete cosegregation with the disease locus in the informative families analyzed (z = 5.27 at theta = 0.00). Other significant linkages were obtained with several markers from Xq11 to q22. With the help of a recently developed genetic map of the region, it was possible to perform multipoint linkage analysis, and the most likely genetic order is DXS1-(SCID, DXS159)-DXYS1-DXYS12-DXS3, with a maximum multipoint logarithm of odds score of 11.0. Our results demonstrate that the SCID locus (gene symbol IMD4) is not closely linked to the locus of Bruton's agammaglobulinemia (a defect in B-cell maturation). They also provide a way for a better estimation of risk for carrier and antenatal diagnosis.

Female↗