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Biomedical subjects

I J Forbes

Publications and source records attributed to I J Forbes.

At least 55 records · Page 3Linked to original sources
PubMed1982

Human B-lymphocyte maturation sequence revealed by TPA-induced differentiation of leukaemic cells.

Normal human B cells and leukaemic B-cell populations in common-type CLL undergo sequential shifts in proportions of the three B-cell subsets, defined by expression of mouse erythrocyte receptors R1 and R2, during TPA-induced differentiation to plasmacytoid cells in vitro, suggesting that the B-cell differentiation pathway is R1 +R2+ leads to R1 -R2+ leads to R1 -R2- leads to immature plasmacyte. Maturation of the less common type of CLL with a predominance of R1 -R2+ type cell was in agreement with this model. Changes in Fc gamma, Fc mu and C' receptors were also observed during maturation. A model of human B-cell maturation is presented on which common sites of blockage in leukaemia can be located.

B-Lymphocytes↗
PubMed1982

Two maturation-associated mouse erythrocyte receptors of human B cells. I. Identification of four human B-cell subsets.

Using rosetting tests with untreated mouse erythrocytes (M) and pronase-treated M (pro M), four human B cell subsets can be identified. Three of these, possessing the phenotypes BM+ pro M+, BM- pro M+ or BM- pro M-, constitute 17%, 61% and 22% of normal blood B cells respectively. The fourth subset, BM+ pro M-, does not occur in normal tissues but was found in the pre-B-cell line of Raji cells, indicating that this phenotype may be a marker for early B cells. Some differences in the proportion of each subset were found in cord blood, lymph nodes and tonsils. Surface-immunoglobulin-positive (SIg+) and -negative (SIg-) non-T cells were present in each subset. M and pro-M rosetting tests were applied to cells from blood of 27 cases of chronic lymphocytic leukaemia (CLL) and to cells from involved nodes, spleen or marrow in five cases of non-Hodgkin's lymphoma (NHL). In 15 cases of CLL, there was considerable increase in the BM+ pro M+ subset (BM+ pro M+ type CLL); in seven cases, there was a predominance of BM- pro M+ cells and in another four cases, BM- pro M- cells predominated. All five cases of NHL were greatly enriched in BM- pro M- cells. There was no obvious correlation between rosetting and other surface markers but BM- pro M- clones in CLL or NHL always stained brightly with FITC-anti-Ig. This was not found in BM+ pro M+ or BM- pro M+ clones. Rosette formation of neuraminidase-treated B cells with M identifies the same subset as B-pro-M rosetting in normals and CLL. Evidence is presented that two types of receptors are involved in M and pro-M rosetting, designated R1 and R2, binding to corresponding M ligands L1 and L2. M rosetting is due to R1-L1 binding while R2-L2 binding mediates B-pro-M rosetting. Shifts between subsets within the same clone in some cases of CLL suggest that the subsets are distinct maturational stage of B-cell development rather than families of B cells of different lineage. The following B-cell maturation sequence is proposed: R1+ R2- lead to R1+ R2+ leads to R1- R2+ leads to R1- R2-.

Adult↗
PubMed1982

Two maturation-associated mouse erythrocyte receptors of human B cells. II. Isolation and partial characterization of a B-cell lectin with specificity of R1.

Trypsin treatment of chronic lymphocytic leukaemia (CLL) cells which have the capacity to rosette with mouse erythrocytes (M), the BM+ subtype, inhibits their capacity to rosette and releases a substance into the supernatant which agglutinates mouse and rat erythrocytes but not erythrocytes of five other species tested. This substance has been named immature B-cell lectin (IBL). The specificity of IBL was further demonstrated by fluorescence labelling, absorption and latex rosetting. IBL does not bind to pronase-treated M (pro M), indicating that it has the specificity of R1 as distinct from R2 which binds to a pronase-resistant ligand on M. Other evidence that IBL is associated with B-cell membrane receptors for mouse erythrocytes is as follows: (1) The amount of IBL released into the supernatant correlated with the trypsin sensitivity of M rosetting with different clones of BM+ CLL cells. (2) Only small amounts of IBL were released from non-rosetting cells (T cells and mature B cells). (3) Binding properties of IBL were inhibited by extract of M but not extract from ox erythrocytes. (4) High-titre solutions of IBL conferred the capacity to form M rosettes on certain types of non-rosetting B cells. IBL has a dual binding specificity. Its binding to M is inhibited by fetuin and mannan, while its binding to B cells is not inhibited by these substances. The relationship of IBL to other membrane lectins including fibronectin is discussed. Preliminary characterization indicates a high-molecular-weight (at least 300,000 daltons) glycoprotein which has a pronounced tendency to aggregate in solution. The relationship of IBL to stages of human B-cell maturation is discussed.

Animals↗
PubMed1981

Loss of receptor activity for mouse erythrocytes precedes tumour promoter-induced maturation of chronic lymphocytic leukaemia cells.

The tumour promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) induced differentiation in lymphocytes from patients with chronic lymphocytic leukaemia (CLL). The differentiation was detected by the appearance of cytoplasmic immunoglobulin (CIg) and a plasmacytoid morphology, and was accompanied by the loss of the ability of the CLL cells to rosette with mouse erythrocytes (M). Loss of M rosetting occurred rapidly (within 10 min), was not prevented by cycloheximide or actinomycin D and was elicited by low concentrations of TPA (ED50 8 X 10(-10) M). Inhibition of rosette formation was induced by other phorbol diester promoters, but not non-promoting derivatives. Loss of the capacity to form M rosettes occurs before events which are evidently related to genome activation.

Animals↗
PubMed1981

Node-based T cell lymphoma. The clinical, immunological and morphological spectrum.

Four cases of node-based T cell lymphoma are presented. The tumours had 2 distinct morphologic patterns. Two cases showed a polymorphous proliferation of pleomorphic lymphoid cells, small lymphocytes, epithelioid cells and arborizing small vessels while the others displayed a monomorphous infiltrate of large atypical lymphoid cells characterized by granular nuclei with numerous tortuous folds to produce a 'squiggly' appearance. One case showed a progression from one histological pattern to the other. Confirmation of the T cell nature of these lymphomas was based on the demonstration of E-rosette formation by morphologically atypical lymphoid cells which also stained positive for acid alpha-naphthyl acetate esterase activity. The patients had an average age of 52 yr and presented with a variable distribution of lymphadenopathy and a predominance of extranodal involvement. Two cases disclosed hypergammaglobulinaemia, one of whom had a paraproteinaemia of IgM-k type. All patients responded poorly to standard combination chemotherapy, 2 expiring 48 and 53 mth after onset of symptoms.

Adult↗
PubMed1981

B lymphocyte specificity of lectins of Cepaea nemoralis and Dolichos biflorus: paradoxical binding of anti-A active lectins to human lymphocyte subclasses.

Binding of four blood group A-specific lectins, from Helix pomatia (HP), lucorum (HL), Cepaea nemoralis (CN) and Dolichos biflorus (DB) to human lymphocytes was determined. Use was made of lectins attached to latex particles, as convenient probes to detect binding of lectins to individual cells, Specificity of lectin-latex probes was demonstrated by comparison with agglutination and fluorescent lectin binding; experiments with untreated and enzyme-treated human and animal erythrocytes confirmed the specificity of the lectin-latex beads as did inhibition in the presence of N-acetyl-galactosamine, the immunodominant sugar of blood group A substance. The binding of HP to T cells and a proportion of B, and non-B, non-T cells is confirmed. Binding to B cells in chronic lymphocytic leukaemia (CLL) is also confirmed. HP-latex had the same specificity as soluble HP, but binding did not require pretreatment of lymphocytes with neuraminidase. HL-latex had the same specificity for erythrocytes, normal lymphocyte subpopulations and CLL lymphocytes as HP, but the binding was weaker and required pretreatment of the lymphocytes with neuraminidase to demonstrate it. Contrary to expectation, CN and DB bound to B lymphocytes and did not bind to T lymphocytes. CN binding was almost completely restricted to B cells, whereas DB bound to part of the non-B, non-T populations as well as to a substantial proportion of B cells. Neither CN nor DB labelled malignant T cells. Both CN and DB bound to B cells in CLL. As with HP, pretreatment of lymphocytes with neuraminidase increased the accessibility of receptors, but was not essential to demonstrate labelling with CN-, and DB-latex preparations. Binding of each lectin to lymphocytes was independent of ABO blood group of donor suggesting that ABO antigens may be expressed poorly, if at all, on lymphocytes. Binding is probably due to additional specificities possessed by these lectins. Protease treatment destroyed CN- and DB-binding sites but not HP receptors suggesting that at least two types of binding site are involved.

ABO Blood-Group System↗
PubMed1980

Phototherapy of human tumours using haematoporphyrin derivative.

Photoradiation therapy (phototherapy) is a recently introduced treatment for malignant tumours, which depends on the activation of a photoreactive drug selectively localized to tumours. An experience in 27 patients with haematoporphyrin derivative is described. The haematoporphyrin derivative was activated by light of 630-nm wavelength, which was delivered to cutaneous tumours from a specially designed incandescent lamp and to deep tumours through a quartz fibre from a laser system. Tumours were eradicated in five patients and incomplete tumour destruction was observed in 14 others. The only significant side effect was temporary cutaneous photosensitivity. This form of treatment has considerable potential, particularly when other treatments have either failed or cannot be applied. However, it is premature to formulate indications for its use. Rapid technological developments can be anticipated which will greatly enhance the efficacy of photodynamic destruction of tumours.

Adenocarcinoma↗
PubMed1980

Preferential epidermotropism in adult t-cell leukemia-lymphoma.

Three patients with systemic T-cell leukemia-lymphoma presented with generalized pruritic skin rash which was clinically nondiagnostic. Biopsies revealed infiltration of the superficial dermis by atypical lymphoid cells with epidermal exocytosis (Pautrier abscesses) producing a pattern of histologic involvement indistinguishable from that of mycosis fungoides and Sézary syndrome. This striking similarity suggests that the phenomenon of preferential epidermotropism is not confined to mycosis fungoides and Sézary syndrome, but may be a property shared by other subpopulations of T-lymphocytes.

Aged↗
PubMed1980

Lymphocyte subpopulations in human lymph nodes: a normal range.

Detailed surface marker studies were performed on 21 nodes from control subjects, 12 normal and 9 showing reactive hyperplasia. Reactive nodes showed a significantly decreased proporation of T lymphocytes (median 44%) and increased proportion of B lymphocytes (median 32%) when compared with normal nodes (median 68% and 18%, respectively). The increase in B lymphocytes was seen in all immunoglobulin classes studied. The values for normal nodes were comparable with three previous studies of nodes confirmed to be normal by histology. On the other hand, the results from reactive nodes were similar to the majority of previously published "control" nodes, many of which were histologically abnormal. The importance of ensuring that control nodes are histologically normal is emphasized by this study.

B-Lymphocytes↗
PubMed1979

Null cell chronic lymphocytic leukaemia.

Lymphocytes lacking receptors for sheep erythrocytes and surface immunoglobulin were present in the blood in large numbers at some stage in four cases of chronic lymphocytic leukaemia (which included a mother and son), and formed a substantial proportion of the circulating lymphocytes in other cases. These null cells possessed receptors for mouse erythrocytes. Other B-cell markers were also found on these cells. Serial studies showed a great variation in the number of null cells during the course of the disease (which may be associated with treatment), suggesting variation in the the maturation of leukaemic cells, and indicating that the surface marker complement may not reflect the constitution of the cell undergoing the original malignant change.

Aged↗
PubMed1979

Immunosuppression in bancroftian filariasis.

Immunological function in Filipino patients with bancroftian filariasis, manifested as either asymptomatic microfilaraemia or chronic obstructive disease, was compared with that found in healthy control subjects living in the same area. As a group, patients with filariasis had raised serum IgG levels, impairment of antibody responses to tetanus and typhoid vaccines, and suppression of delayed hypersensitivity skin reactions to heterologous antigens. This immunosuppression in filariasis may result from antigenic competition and may contribute to the development of secondary infections.

Antibody Formation↗
PubMed1979

Radiation-related coronary artery disease in Hodgkin's disease.

Coronary artery disease is a rare and only recently recognised complication of mediastinal irradiation. A 34-year-old man died suddenly eight years after mediastinal irradiation for Hodgkin's disease. Autopsy disclosed severe narrowing of all major extramural coronary arteries by atherosclerotic plaques whereas all other systemic and visceral arteries were virtually free of atheroma. Autopsy findings in the five reported cases of radiation-related coronary artery disease are reviewed.

Adult↗
PubMed1979

Surface marker studies in chronic lymphocytic leukaemia and non-Hodgkin's lymphoma.

Immunological surface marker techniques were applied in a study of 29 cases of chronic lymphocytic leumaemia and 22 of non-Hodgkin's lymphoma. Surface marker characteristics distinguished 2 subtypes of B lymphocytes. Chronic lymphocytic leukaemia was a monoclonal proliferation of B lymphocytes which produced spontaneous rosettes with mouse erythrocytes and had faintly immunofluorescent surface immunoglobulin. The majority of non-Hodgkin's lymphomas also had their origin from B lymphocytes but in contrast, this subtype did not show receptors for mouse erythrocytes and their surface immunoglobulin was brightly staining and demonstrated "capping". The clonal origin of nodular lymphomas could also be demonstrated on frozen sections stained for surface immunoglobulin. Two cases of true histiocytic lymphoma were identified. The current information available on surface marker characteristics of the leukaemias and lymphomas is reviewed.

Adult↗