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Biomedical subjects

M Bofill

Publications and source records attributed to M Bofill.

At least 73 records · Page 4Linked to original sources
PubMed1986

Myasthenia gravis: immunohistological heterogeneity in microenvironmental organization of hyperplastic and neoplastic thymuses suggesting different mechanisms of tolerance breakdown.

Four samples of thymoma obtained from patients affected by myasthenia gravis have been immunohistologically analysed on cryostat sections using a panel of antisera and monoclonal antibodies specific for antigens which define different stages of intrathymic lymphocyte differentiation and antigens specific for different types of thymic epithelial cells (cortical, medullary). When the thymoma samples were compared to age-matched normal thymuses and hyperplastic thymuses obtained from patients with myasthenia gravis some evident microenvironmental differences could be demonstrated using these reagents. In all the thymoma samples in fact the neoplastic lobules appeared as grossly enlarged cortical-type areas, formed by accumulations of T lymphocytes exhibiting the cortical immature phenotype (TdT+, T6+, etc.) within a network of putatively neoplastic epithelial cells characterized by cortical phenotype as defined by reactivity with various monoclonal antibodies (RFD4-, MR3+). These 'cortical' epithelia showed some abnormal features such as lack or irregular distribution of HLA-DR and enhanced keratin expression. Small areas of 'medullary' differentiation could be observed in 3/4 thymoma samples. In thymic hyperplasia, on the other hand, the cortical areas appeared somewhat compressed (but comparable to those observed in normal age-matched samples) by enlarged medullary areas. The expansion of medullary areas was due to the infiltration of 'peripheral' lymphoid tissue intruding through the extraparenchymal zone and forming organized B and T areas. These observations are discussed in the light of the clinical heterogeneity observed in myasthenia gravis.

Adolescent↗
PubMed1986

HTLV-III/LAV viral antigens in lymph nodes of homosexual men with persistent generalized lymphadenopathy and AIDS.

The presence of core antigens of retrovirus HTLV-III/LAV, referred to as "AIDS-related virus" (AV), has been sought in lymph node samples of patients with persistent generalized lymphadenopathy (PGL, 28 patients), prodromal AIDS (1 patient) and AIDS with Kaposi sarcoma (3 patients). In 30 patients the deposition of viral antigens, detected by monoclonal antibodies to HTLV-III and LAV, could be observed within the germinal centers (GCs) primarily within the extracellular network of immune complexes, and the two patients who were negative were atypical. No AV could be found in normal tonsil or in samples with follicular hyperplasia of unknown etiology (20 cases). These findings, taken together with the ultrastructural identification of typical retrovirus particles in all 9 PGL and 2 AIDS cases studied, indicates that the network of follicular dendritic (FD) cells is an important reservoir of AV virus antigen at this site. The persistence of this retrovirus inside the GCs helps explain how the follicular hyperplasia affecting FD cells and B blasts in PGL may in progressive cases be accompanied by destruction of FD cells and gradual development of T4+ lymphopenia. T4+ T cells may circulate through the GCs and become infected with AV there. In addition, the identification of retrovirus antigen in situ may be of diagnostic value.

Acquired Immunodeficiency Syndrome↗
PubMed1985

Relationships between blood product exposure and immunological abnormalities in English haemophiliacs.

Amongst 160 English haemophiliacs treated with clotting factor concentrates, abnormalities of T lymphocyte subset distribution (characterized by low T4/T8 ratios and high total T8 counts), low in vitro phytohaemagglutinin stimulation and raised serum IgG levels, were more common in patients with haemophilia A than B, in patients who had received heavier blood product exposure, and in adults rather than children. A slight reduction in lymphocyte and platelet counts was found in 26% and 17% of patients. In the sample of patients tested, serum alpha 1-thymosin levels were often raised, but beta 2-microglobulin levels were usually normal. Fractionation procedures used to prepare clotting factor concentrates, and the amounts of concentrate used, are more likely to be causally related to these immunological abnormalities than the origins of source donor plasmas.

Adolescent↗
PubMed1985

Human B cell development. II. Subpopulations in the human fetus.

In man, during fetal development the B cell populations show distinct phenotypes at different tissue sites. The pre-B and B lymphocytes of the fetal liver and bone marrow express IgM and B cell markers, B1 (CD20) and BA-1 (CD24). These "early" cells are negative with a number of other reagents, anti-IgD, RFB4 (CD22), RFB6 (CD21), and RFA-2, which on the other hand recognize peripheral B cells. These peripheral B lymphocytes in the developing fetus are heterogeneous. The diffusely distributed B cells in the earliest lymph node samples, 16 to 17 wk of gestational age, and from 16 to 21 wk in the spleen, are strongly IgM+ (IgD+,RFB4+,RFB6+, and RFA-2+) but lack T cell-associated markers such as T1 (CD5, p 67,000 dalton equivalent of murine Ly-1) and Tü-33. In fetal lymph nodes, primary nodules develop around the follicular dendritic (FD) cells from 17 wk onward, and contain a virtually pure population of B cells; B1+,BA1+,RFB4+,RFB6+,RFA-2+, which simultaneously express IgM,IgD together with T1 (CD5), a T cell-associated antigen. A sizeable subpopulation of these IgM+,T1+ cells are also positive for Tü-33, another T cell-associated marker. In the spleen, the B cells of the IgM+,IgD+,T1+ type appear in smaller numbers and only relatively late around wk 22. These cells are diffusely distributed at first, and start accumulating around the small FD cell clusters as soon as these emerge about the 23rd gestational wk. At that time, the IgM+,T1+B cells can also be washed out from the peritoneal and pleural cavities. The T1+,IgM+B cells may represent the normal equivalent cells of B chronic lymphoid leukemia and centrocytic lymphoma, and appear to be the counterpart of Ly-1+,IgM+B cells in the mouse.

Adult↗
PubMed1985

Microenvironments in the normal thymus and the thymus in myasthenia gravis.

The disposition of epithelial cells and extracellular matrix, in the thymus of 8 cases of myasthenia gravis (MG) and in controls (over a wide age range) was studied. In the controls, the subcapsular epithelium was strongly Leu-7-positive in the fetus, negative in childhood, and positive again in adults. Another antibody, RFD4, also labeled the subcapsular epithelium in childhood and adults, but not fetal samples. The samples from MG cases showed the same staining pattern as adult control samples. The medullary epithelium was also RFD4+, and at all ages. The most striking changes in the advanced cases of MG were the unusual arrangement and hypertrophic appearance of medullary epithelial cell areas, separated by laminin-positive basement membranes from the alternating multiple bands of peripheral lymph-node-like areas. The latter had regions resembling the paracortex of lymph nodes as well as germinal centers (GCs). The T-cell zones contained heavy deposits of fibronectin. These T-cell zones were unique to the thymus in MG and were absent in the two normal thymic samples with isolated GCs. In MG the laminin-containing basement membrane, which separated the medullary epithelial and peripheral lymph-node-like areas, was fenestrated at circumscribed points closest to the GCs, thus apparently permitting communication among the medullary epithelium, the T-cell zones, the GCs and the associated antigen-presenting cells. Large numbers of interdigitating cells and some lymphocytes of cortical thymocyte phenotype were also found at these special sites, where opportunities for autosensitization may persist in MG.

Adult↗
PubMed1985

An immunohistological approach to persistent lymphadenopathy and its relevance to AIDS.

Recent evidence has shown that not only AIDS but also the majority of 'unexplained' persistent, generalized lymphadenopathy (PGL) are related to HTLV-III/LAV infections. The early detection how these changes may proceed to AIDS then become a prime interest. Eleven patients with PGL (10 homosexual males and one heterosexual haemophiliac) have been studied by immunohistology using monoclonal antibodies to dendritic reticulum cells of the germinal centre, T and B lymphocyte subsets, plasma cells and factor VIII, as an endothelial marker. In six cases only follicular and paracortical hyperplasia was detected, while in five other cases destruction of the dendritic reticulum cell network was seen with this sensitive method. This early destruction may explain the release of activated B cells into the circulation and prove to be an ominous prognostic sign, as it appears to correlate with 'prodromal' symptoms. In four out of 11 cases the depletion of T4+ cells in the paracortex was not as severe as in the blood, indicating that T4+ cells may preferentially settle in tissues at the time of T4 lymphopenia. In addition, germinal centres contained an additional patchy infiltration of T8+ cells. A patient with Kaposi's sarcoma did not show germinal centre destruction but did reveal extensive plasma cell infiltrates. Immunohistology may contribute to the definition of prognosis and analysis of disease progression in patients with PGL.

Acquired Immunodeficiency Syndrome↗
PubMed1985

Human macrophages and T-lymphocyte subsets infiltrating nodules of Onchocerca volvulus.

The nature of the lymphoid infiltrate in nodules of Onchocerca volvulus was assessed using monoclonal antibodies to lymphoid cell surface markers. Although B cells were generally absent, T cells were present, but in variable amounts. The ratio of T4+ (helper phenotype) to T8+ (suppressor-cytotoxic phenotype) was usually in the normal peripheral blood range of about 3, although ratios ranging from 1 to 10 were seen in selected areas of the onchocercoma. The possibility of immunosuppression through dominance of T4+, Leu-8+ cells (suppressor-inducer phenotype) within the T4+ population was also excluded. The T cells did not tend to concentrate in close proximity to the parasite, and there was no general bias in favour of the T suppressor cell phenotype (T8) within the infiltrate. Macrophages and dendritic cells were consistently observed and consisted of three defined cell types in approximately equal proportions: normal, unactivated macrophages (HLA-DR-, acid phosphatase positive), activated macrophages (HLA-DR+, acid phosphatase positive) and cells of dendritic morphology (HLA-DR+, acid phosphatase negative). These results are discussed in relation to immune suppression in filariasis.

Antibodies, Monoclonal↗
PubMed1985

Human B cell development. I. Phenotypic differences of B lymphocytes in the bone marrow and peripheral lymphoid tissue.

The phenotype of B lineage cells (TdT+, pre-B, IgM+, IgD-, and IgM+,IgD+) in infant and adult human bone marrow was compared with that of B cells seen in peripheral tissues such as tonsil and blood. The range of B cell-associated antibodies used included four reagents with greater than 90% reactivity on peripheral B cells: RFB4 and To15 (both p135, corresponding to CD22), RFB6 (p140 corresponding to CD21), and Y29/55, a unique B cell-specific antibody. In addition, AL-1, an antibody with virtually no reactivity against peripheral B cells was also used. The BM cell subpopulations were heterogeneous in respect of antibody reactivity. The TdT+, pre-B and IgM+, IgD- cells were AL-1+ but did not express membrane antigens recognized by the antibodies To15, RFB4 (CD22), and RFB6 (CD21). TdT+, pre-B cells, and 50% of IgM+, IgD- BM B cells were also unreactive with antibody Y29/55, the other 50% being Y29/55+. In contrast, the IgM+,IgD+ BM B cells, like peripheral B cells, were positive with antibodies To15, RFB4, RFB6, and Y29/55, but reacted only in small numbers with AL-1. The orderly differentiation-linked display of these antigens was also suggested by the findings that normal TdT+, pre-B, and IgM+,IgD- cells expressed the To15 and RFB4 (CD22) antigens in their cytoplasm (in the Golgi region). This observation was confirmed in malignant common acute lymphoblastic and pre-B blast cells, as well as in the corresponding permanent cell lines KM3 and NALM-6. In these lines the membrane expression of To15 and RFB4 could be induced by phorbol ester during a 48 to 72 hr culture period.

Adolescent↗
PubMed1984

Intestinal lymphocyte subpopulations in inflammatory bowel disease: an analysis by immunohistological and cell isolation techniques.

Lymphocyte subpopulations in the intestinal mucosa of patients with ulcerative colitis or Crohn's disease have been studied using a double marker immunofluorescence technique. Analysis of tissue sections revealed that the majority of intraepithelial lymphocytes (IEL) were T cells (Hle-1+ HuTLA+ UCHT1+). Of these, over 80% were of suppressor-cytotoxic phenotype (OKT8+:83 +/- 10.2%) with a small population of helper type IEL (OKT4+). Only one third of OKT8+ IEL reacted with the T cell antibody, anti-Leu-1. IEL were also Tac-, C3b-receptor- (C3RT05-), and Ig-. Within the lamina propria, OKT4+ T cells predominated (ulcerative colitis 64 +/- 6.0%; Crohn's disease 63 +/- 6.0%). Less than half of the smaller OKT8+ population in the lamina propria was Leu-1+. These finding did not differ from those seen in histologically normal tissues from controls, and are similar to those reported in the small intestine. Mononuclear cells were also isolated from the intestinal lamina propria using an enzymatic technique. The majority of lymphocytes obtained were T cells (OKT3+), with populations of OKT4+ and OKT8+ cells. Comparison of the ratio of OKT4+ to OKT8+ lymphocytes determined by immunohistological analysis with that obtained in mucosal isolates, however, suggested that the isolation procedure may deplete OKT8+ cells. These findings indicate that an imbalance of mucosal immunoregulatory T cells, as defined by monoclonal antibodies, does not occur in inflammatory bowel disease. They also emphasize that functional studies of isolated intestinal mucosal cells should be combined with morphological studies of cell populations in situ.

Adolescent↗
PubMed1984

Distribution and heterogeneity of cells detected by HNK-1 monoclonal antibody in blood and tissues in normal, reactive and neoplastic conditions.

When studied with double staining techniques HNK-1+ cells include subsets not expressing T cell antigens (A), expressing T8 antigens (B) and expressing T4 antigens (C). Cells with phenotype A are observed as the dominant HNK-1+ population (greater than 50% of all HNK-1+ cells) in the blood from controls and from patients with solid tumours, infectious mononucleosis and sarcoidosis. Cells with phenotype B are always a substantial subset (35% of HNK-1+ cells) in the peripheral blood but in patients with B chronic lymphocytic leukaemia and angioimmunoblastic lymphadenopathy these cells are present in an even higher percentage (greater than 50% of all HNK-1+ cells). This cell subset is the only HNK-1+ population found in the few tumour samples where HNK-1+ cells are identifiable. Apart from these few cases of malignancies, the type A and B subsets are rare in the tissues. In these samples Leu 11+ cells seem to be absent. In contrast, cells with phenotype C are a minor population in the blood but represent most HNK-1+ cells in the germinal centres of lymph nodes and their malignant counterparts in follicular centre cell lymphoma. These HNK-1+, T4+ cells are Leu 11-. These phenotypic characteristics indicate that the most efficient NK cells may represent a circulating and not a tissue seeking population.

Adult↗
PubMed1983

Routine immunofluorescent and histochemical analysis of bone marrow involvement of lymphoma/leukaemia: the use of cryostat sections.

Enzyme histochemical and immunohistological (immuno-fluorescence and -peroxidase) techniques have been routinely used for investigating over 70 normal and pathological bone marrow samples. This recently standardized diagnostic procedure is very quick and can be performed in a few hours. In 6 cases the clinical diagnosis of leukaemia/lymphoma has become apparent only after the immunohistological analysis of the bone marrow. In 6 other cases the information about the staging of B cell malignancies was superior in the frozen biopsies to the paraffin embedded preparations. Amongst many other features the monoclonality of B CLL/lymphomas, the special features of B CLL infiltrates (RFA-1+, Leu-1+, HLA-DR+, SmIg+), follicular lymphoma deposits (containing follicular dendritic cells) and non-T, non-B acute lymphoblastic leukaemic blasts (terminal transferase+, HLA-DR+) as well as the sometimes conspicuous presence of infiltrating normal T cells could be clearly and reproducibly demonstrated.

Adolescent↗
PubMed1983

Lymphocyte subpopulations in the human small intestine. The findings in normal mucosa and in the mucosa of patients with adult coeliac disease.

Lymphocyte subpopulations in human small intestinal mucosa have been studied using an immunofluorescence technique on tissue sections. In the normal intestine, the majority of intraepithelial lymphocytes (IEL) were of suppressor-cytotoxic phenotype (HuTLA+ UCHTI+ OKT8+ OKT4-; 84%). Only one-third of these OKT8+IEL reacted with anti-Leu-1, and antibody directed towards a 67,000 dalton antigen found on peripheral blood T cells. IEL failed to express the activation antigen, Tac, and also lacked detectable C3b receptor (C3RTO5-). The remaining T IEL, as well as the predominant lamina propria T lymphocytes (LPL), were OKT4+ OKT8-, helper type T cells. Most of the lamina propria OKT8+ cells were also Leu-1-. In patients with adult coeliac disease, the proportions of OKT8+ and OKT4+ lymphocytes in the epithelium were not altered. However, the proportion of OKT8+ Leu-1+TIEL was significantly increased (56 vs 32%; P less than 0.02). IEL were also HLA-DR-, Tac- and C3RTO5-. The proportion of OKT8+ cells in the lamina propria was slightly, but significantly, increased (40 vs 32%; P less than 0.005). Mucosal findings in treated patients did not differ from normal. Lymphocytes with the phenotype of natural killer cells (HNK-1) were rarely found in normal or diseased mucosa. No alterations in the proportions of circulating T lymphocytes or their subsets were found in patients with coeliac disease. These findings illustrate the heterogeneity of lymphocyte subpopulations in normal and in diseased small intestinal mucosa. The changes found in adult coeliac disease may reflect the increased traffic of IEL into the epithelium.

Adult↗
PubMed1983

T cell regeneration after allogeneic bone marrow transplantation.

Various T cell subsets were characterized by double immunofluorescent staining using monoclonal antibodies (MoAb) in blood, bone marrow (BM) and tissues of 29 patients after allogeneic BM transplantation (BMT). In an attempt to prevent graft versus host disease (GvHD), 15 patients received cyclosporin A (Cy A). In the remaining 14 patients the BM was pre-incubated with a MoAb, OKT3. The regeneration of T4+ subset was delayed and the level of T8+ cells was abnormally high even 1 year after engraftment. This did not have any predictive value for the appearance of complications such as GvHD or severe viral infections. The number of T8+ cells was lower in the group of patients who received Cy A than in the OKT3 group (0.7 +/- 0.2 vs 1.5 +/- 0.3 X 10(9)/1 at day 90). In contrast to normal individuals, the T4/T8 ratio in both blood and regenerating BM of BMT patients was less than 1. A sizeable subset of circulating T cells expressed the phenotype T8+, T10+, HNK-1+, DR+. Circulating cells of this phenotype were transiently very high (up to 50%) in patients with active GvHD or suffering from severe viral infection. This subpopulation of lymphocytes was not found in the epidermal infiltrate that accompanied GvHD where the predominant phenotype was T8+, T1-, T10-, HNK-1-, DR-. We conclude therefore that after BMT the number and phenotype of circulating T cells reflects the T cell distribution seen in the regenerating BM.

Adolescent↗