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Biomedical subjects

M L Rose

Publications and source records attributed to M L Rose.

At least 109 records · Page 6Linked to original sources

Analysis of T cell subpopulations and cyclosporine levels in the blood of two neonates born to immunosuppressed heart-lung transplant recipients.

The influence of continuous immunosuppression on the immune system of 2 neonates born to heart-lung transplant recipients was analyzed. T cells, T cell subpopulations, B cells and cyclosporine levels were measured in maternal and cord blood at the time of delivery. Cyclosporine, both parent compound, and metabolites were found in cord blood but in lower amounts than that in the mother. This discrepancy was more pronounced for parent compound than metabolites. Infants born to immunosuppressed mothers had more T and B cells than the mother and had similar numbers of T and B cells to that found in cord blood from 10 babies born to nonimmunosuppressed mothers. One infant had fewer activated T cells and a higher CD4/CD8 ratio due to increased numbers of CD4 cells than normal. In conclusion, neither of these babies had a lymphocyte profile suggestive of chronic immunosuppression.

Antigens, Differentiation↗

Expression of MHC antigens in normal human lungs and transplanted lungs with obliterative bronchiolitis.

Immunocytochemical techniques have been used to investigate the expression of common determinants of class I, common determinants of class II and DR, DP, and DQ antigens on frozen sections from twenty normal donor lungs, three lungs resected due to carcinoma and nine lungs removed from heart/lung recipients who were undergoing retransplant due to obliterative bronchiolitis. In all lungs, alveolar macrophages expressed common determinants of class I and class II, as well as DR, DP and DQ antigens. In normal lung, class I was expressed on all vascular endothelium, all tracheal epithelium and most, but not all, bronchiolar epithelium. Class II was always expressed on tracheal epithelium, but expression on bronchiolar epithelium and vascular endothelium was variable and sometimes absent. In lungs from transplant patients with severe obliterative bronchiolitis, vascular endothelium, in addition to expressing class I, now consistently expressed class II. Epithelium from trachea, bronchioles, and alveoli also consistently expressed class I and class II. To conclude, there is enhanced expression of class II antigens on endothelial and epithelial cells from lungs with obliterative bronchiolitis.

Bronchi↗

End-stage dilated cardiomyopathy. Persistence of enterovirus RNA in myocardium at cardiac transplantation and lack of immune response.

Tissue from the explanted hearts of 21 patients with idiopathic dilated cardiomyopathy or 19 patients with other specific heart muscle diseases were investigated for presence of enterovirus-specific RNA with an enterovirus group-specific cDNA probe. This was complementary to coxsackievirus B2 RNA sequences between nucleotide numbers 6,550 and 7,400, which are highly conserved between enteroviruses. Hearts from six patients with dilated cardiomyopathy and one patient with ischemic heart disease were found to contain virus RNA. Serology revealed that only one patient (dilated cardiomyopathy group) was positive for coxsackievirus B-specific IgM but negative for virus RNA in the myocardium. Quantitation of leukocytes and T-lymphocytes in the myocardium and expression of major histocompatibility locus antigens revealed no significant differences associated with persistence of virus RNA. These data demonstrate that enterovirus RNA persists in myocardium of a significant proportion of patients with end-stage dilated cardiomyopathy in the absence of a continuing cell-mediated or humoral immune response.

Adolescent↗

Expression of class I and class II major histocompatibility antigens in normal and transplanted human heart.

The expression of monomorphic determinants of class I and class II histocompatibility antigens in human heart before and after cardiac transplantation was examined using monoclonal antibodies and an immunoperoxidase technique. Thirty-five biopsy specimens were examined. Seven were from nontransplanted hearts and 28 were from patients who had received orthotopic cardiac transplantation 5-270 days previously. In normal hearts no class I was found on the surface of the myocardium, but intercalated discs were occasionally stained and interstitial structures (blood vessels and discrete mononuclear cells) strongly expressed the antigen. In contrast, of the 28 specimens from transplanted patients, 24 expressed class I antigen strongly on the outer surface and intercalated discs of the myocardium as well as on the interstitial structures. Class II antigen was not found on the myocardium of normal heart. It was present on small capillaries, the endothelia of some large capillaries, and discrete mononuclear cells. In 20 of 25 samples from transplant patients there was increased expression of class II antigen on interstitial structures but not on myocardium. The increased expression of class I antigen on the myocardium following transplantation may make it a potential target for cytotoxic T cells. The relevance of increased expression of class I and class II antigens in response to transplantation is discussed.

Adolescent↗

Increased expression of HLA ABC class I antigens by muscle fibres in Duchenne muscular dystrophy, inflammatory myopathy, and other neuromuscular disorders.

The distribution of HLA ABC class I antigens in human skeletal muscle obtained by needle biopsy was investigated by means of a monoclonal antibody (W6/32) and an immunoperoxidase technique. Five samples from normal individuals and twenty-nine from patients with various neuromuscular disorders were examined. Normal muscle fibres and those from patients with congenital muscular dystrophy expressed little or no class I antigens, whereas muscle fibres of patients with myositis and various X-linked muscular dystrophies showed consistently strong expression. In other neuromuscular diseases expression was more variable. The presence of class I antigens on diseased muscle fibres may render them susceptible to cytotoxic T cells; these antigens may thus have an important role in the destruction of muscle fibres.

Adolescent↗

Normal values for the different classes of venous blood mononuclear cells defined by monoclonal antibodies.

We present the data obtained from routine quantitation of normal venous blood mononuclear cells using 19 monoclonal antibodies against defined mononuclear cell surface antigens. The results indicate different values for percentage and absolute numbers of T lymphocytes and of T lymphocyte subsets depending on the monoclonal antibodies used to quantify these populations. In most instances the total number of identified cells was significantly less than the total number of recovered blood mononuclear cells, which suggests the existence in blood of a null cell population. Evidence is advanced to support previous observations that at least a proportion of this population is of B cell lineage, expressing cytoplasmic immunoglobulin but lacking other class or lineage specific markers. The value of a diverse monoclonal panel in routine quantitation of peripheral blood mononuclear cells is discussed.

Adult↗

Use of monoclonal antibodies to quantitate T lymphocyte subpopulations in human cardiac allografts.

T cell subsets have been quantitated in 40 human cardiac biopsies to characterize the surface phenotype of T lymphocytes involved in acute rejection. Seventeen biopsies were from patients receiving conventional immunosuppression, and 18 were from patients receiving cyclosporine (Cys) as the major immunosuppressive drug. Five biopsies were from nontransplanted hearts. Frozen sections were treated with monoclonal antibodies of the Leu series and an immunoperoxidase technique to determine numbers of Leu 4 (T3 or pan-T-cell), Leu 2a (T8 or suppressor/cytotoxic), and Leu 3a (T4 or helper/inducer) positive cells. Biopsies from patients on conventional immunosuppression during rejection contained 68.3 +/- 10 infiltrating leukocytes/0.048 mm2 of the biopsy, of which 47 +/- 7.4% were T cells. Most of the T cells (86%) were of the 2a/T8 phenotype. In contrast, nonrejecting hearts contained substantially fewer infiltrating leukocytes (43.3 +/- 18.8/0.048 mm2), of which only 12.6% were T cells. There was no predominance of the 2a/T8 subset in nonrejecting biopsies. It is concluded that in patients receiving conventional immunosuppression, rejection is associated with an influx of T cells, most of which are 2a/T8-positive, into the cardiac allograft. In contrast, biopsies from patients on Cys contained large numbers of infiltrating leukocytes that did not appear to correlate with the histological assessment of rejection. However, in these patients, rejection was associated with an increase in the number of T cells with no consistent pattern of subset distribution. Biopsies from nontransplanted hearts contained few infiltrating leukocytes (31.5 +/- 9.4/0.048 mm2), and none of them were T cells.

Antibodies, Monoclonal↗

Staphylococcal protein-A is a potent T-cell mitogen of tonsillar lymphocytes.

Optimal conditions for the stimulation of human tonsillar lymphocytes by staphylococcal protein-A (SpA) are described. By stimulating fractions enriched or depleted of E-rosette forming cells, the response was shown to be predominantly a T-cell response. A comparison of stimulation by SpA with that of phytohaemagglutinin (PHA) proved SpA to be a potent T-cell mitogen. We suggest that SpA may be another useful mitogen for studying human T-cell growth and differentiation.

Humans↗

Binding of peanut lectin to germinal-centre cells: a marker for B-cell subsets of follicular lymphoma?

The binding of horseradish-peroxidase-labelled peanut lectin (HRP-PNL) to cryostat sections of tonsil, lymphoma lymph nodes, reactive lymph nodes and miscellaneous tumours demonstrated that PNL binds selectively to lymphocytes in germinal centres. Lymph nodes from 21 patients with non-Hodgkin's lymphomas were phenotyped as cell suspensions for PNL binding, and the following surface markers: E rosetting, C3d, SIg, OK markers of T-cell subsets, Ig heavy-chain and light-chain classes. There was a positive correlation between PNL binding and cells with SIg and C3d receptors. 4/5 cases of centroblastic/centrocytic follicular lymphoma had a PNL+ SIg+ C3d+ phenotype. Both cases of centroblastic/centrocytic diffuse lymphoma were PNL-. There was no correlation between PNL binding and heavy- or light-chain Ig class. PNL binding and presence of C3d receptors were not always positively correlated, indicating that follicular cells may be either PNL+ SIg+ C3d+ or PNL+ SIg+ C3d-. The binding pattern of PNL to 1 case of thymic hyperplasia and 2 cases of malignant lymphoma lymphoblastic T type suggested that some but not all cortical thymocytes bind PNL.

Adolescent↗

Binding of peanut lectin to thymic cortex and germinal centres of lymphoid tissue.

The binding pattern of horseradish peroxidase conjugated peanut lectin (HRP-PNL) on frozen sections of lymphoid tissue from man, mouse, rat, hamster, guinea-pig, rabbit, sheep and chicken has been investigated. Binding of PNL was found to be highly species dependent; man, mouse and sheep showed strong binding to lymphocytes in thymic cortex and germinal centres; lymphoid tissue from hamster, guinea-pig and rabbit did not stain with HRP-PNL and rat showed only lightly positive cells in thymic cortex and germinal centres; all lymphoid tissue from chicken, except the bursal cortex, bound PNL. Neuraminidase treatment of tissues which did not bind PNL resulted in strongly PNL-positive cells. Double binding studies on murine Peyer's patches with fluorescein isothiocyanate conjugated PNL (FITC-PNL) and tetramethylrhodamine isothiocyanate (TRITC)-anti-Thy-1.2 or anti-immunoglobulin reagents revealed 3%-10% of PNL positive cells to be Thy-1.2 positive and 70%-80% to bear surface immunoglobulin.

Agglutination↗

Peanut lectin binding properties of germinal centres of mouse lymphoid tissue.

Peanut (Arachis hypogaea) lectin (PNL) has been shown to agglutinate the 90% of cells from murine thymus which are supposed to be immature cortical thymocytes. Further studies on the numbers of thymocytes binding fluorescein isothiocyanate conjugated PNL (FITC-PNL) confirmed the large proportion of PNL binding cells. In other organs such as bone marrow, spleen and peripheral lymph nodes, smaller proportions of PNL positive cells have been recorded. PNL-positive cells outside the thymus have been reported to be either Thy 1-positive or null cells. It has also been suggested that PNL binding may be a marker for immaturity not only in relation to T lymphocytes but also amongst haematopoietic stem cells. Thus PNL binding as an aspect of lymphocyte differentiation is a matter of considerable interest. The current study describes the distribution of horseradish peroxidase-conjugated PNL (HRP-PNL) on frozen sections of mouse lymphoid organs. It seems that PNL binds to cells in germinal centres but not to those in some other areas containing activated lymphocytes. There is good correlation between the presence of PNL-binding germinal centres in frozen sections of lymphoid organs and the number of PNL-binding cells counted in cell suspensions from the same organs.

Animals↗