Biomedical subjects

D A Brooks

Publications and source records attributed to D A Brooks.

66 records · Page 4Linked to original sources

PubMed1984

Monoclonal antibody-defined B cell subsets in aging humans and Down's syndrome.

Peripheral blood from aging and young humans and patients with Down's syndrome, and from age- and sex-matched controls, was studied for the proportions of surface immunoglobulin (SIg+) bearing and monoclonal antibodies FMC1, and FMC7 defined B lymphocytes and B lymphocyte subsets using fluorescent-activated cell sorter. In aging humans, the proportion of SIg+ and FMC1+ (that detect all B lymphocytes) were comparable to simultaneously studied healthy young controls. However, FMC7+ (that detects a subset of B cells) B cells were significantly (p less than 0.05) increased when compared to young subjects. In aging subjects, the proportions of FMC7+ B cells were comparable to their FMC1+ B cells, whereas in young subjects FMC7+ B cells were a subset of FMC1+ B cells. In Down's syndrome, a phenomenon similar to aging humans was observed, that is the proportions of FMC7+ were increased when compared to age- and sex-matched controls and were comparable to their own FMC1+ B cells. This study demonstrates the abnormality of B lymphocytes in human aging and Down's syndrome. The significance of these findings is discussed.

Adult↗

PubMed1984

Monoclonal antibodies against antigens of the human platelet surface: preparation and properties.

Three monoclonal antibodies, FMC24, 25 and 27, reactive with human platelets, are described. In normal blood the 3 antibodies are specific for platelets, but FMC27 reacts with leukemic blast cells in a proportion of acute leukemias. FMC25 precipitates the platelet membrane glycoprotein lb and a glycoprotein of molecular weight 22,000. The antibodies show different effects on platelet aggregation.

Acute Disease↗

PubMed1983

The nature of hairy cells - a study with a panel of monoclonal antibodies.

In all 11 patients with hairy-cell leukaemia (HCL) tested, a high percentage of peripheral blood and splenic (3 cases) hairy cells (HCs) reacted with 2 B-cell-specific monoclonal antibodies (FMC1 and FMC7), but failed to stain with 5 monocyte/macrophage-specific (FMC17, UCHM1, SM1, SMø and OKM1) and with 4 T-cell-specific antibodies (UCHT1, Leu1, 2a and 3a). The data provide further evidence in support of the B-cell nature of the HCs of HCL.

Animals↗

PubMed1983

Membrane antigens of human cells of the monocyte/macrophage lineage studied with monoclonal antibodies.

Three monoclonal antibodies, FMC17, FMC32, and FMC33 directed against human cells of the monocyte-macrophage lineage are described. The antibodies react strongly with blood monocytes and weakly, if at all, with granulocytes. Lymphoid cells are not stained. In tissue sections macrophages and interdigitating reticulum cells are stained. Lymphoid leukemia cells generally do not react with the antibodies, while myeloid leukemia cells give a variable pattern, with relatively differentiated cells more likely to react than undifferentiated cells. Differences between the 3 antibodies in their reactivity with leukemic cells and tissue macrophages indicate that they are directed against distinct antigens, which may serve as differentiation markers in the monocyte/macrophage lineage.

Antibodies, Monoclonal↗

PubMed1983

Maturation of human B lymphocytes--studies with a panel of monoclonal antibodies against membrane antigens.

The expression of six different membrane markers by cells of the human B lymphocyte lineage has been studied, using monoclonal antibodies. B cells representing various stages of differentiation/maturation have been examined, using normal cells, leukaemia cells, and continuous cell lines. The expression of the six markers has been compared with maturation stages defined by immunoglobulin expression. The HLA/beta 2-microglobulin complex is present throughout the B cell lineage, whilst the Ia (p28,33) marker is present from the earliest stage that can be attributed to the B lineage, but is lost during plasma cell differentiation. A marker detected by monoclonal antibody FMC 1 is present only on mature B lymphocytes, being absent from pre-B cells or plasma cells. FMC 7 detects an antigen found on a relatively mature subpopulation, whereas FMC 8 detects early as well as mature B cells. FMC 3 expression is found on a proportion of cells at any maturation stage, suggesting that expression of this marker is controlled by factors unrelated to maturation.

Antibodies, Monoclonal↗

PubMed1982

A differentiation antigen expressed selectively by a proportion of human blood cells: detection with a monoclonal antibody.

A monoclonal antibody, FMC 8, has been prepared after immunization with a cell line of the non-T-non-B type acute lymphoblastic leukaemia (ALL). The antigen detected by this antibody consists of a single polypeptide chain with an apparent molecular weight of 24,000 d. The antigen is absent from T cells but appears after mitogen stimulation. It is found on the majority of normal circulating B cells but is absent in most chronic lymphocytic leukaemias. All cells of the non-T-non-B type express the antigen, whereas T-ALL cells generally do not. Granulocytes, monocytes and platelets react with the antibody, but erythrocytes do not. The wide but selective distribution of the antigen renders FMC 8 potentially useful, together with other monoclonal antibodies, in the delineation of differentiation pathways and in phenotypic analysis of leukaemia and lymphoma cells.

Animals↗

PubMed1981

Human lymphocyte markers defined by antibodies derived from somatic cell hybrids. IV. A monoclonal antibody reacting specifically with a subpopulation of human B lymphocytes.

The technique of somatic cell hybridization has been used to produce a monoclonal antibody (designated FMC7) against the human B lymphoblastoid cell line HRIK. By indirect immunofluorescence FMC7 reacted with a total of 3 out of 10 B cell lines, but failed to bind T and Null cell lines. On normal peripheral blood, FMC7 bound between 3 and 6% of mononuclear cells. When normal peripheral blood mononuclear cells were fractionated, FMC7 reacted with only the B-enriched fraction, staining some but not all cells expressing SMIg. Double marker analysis indicated that the antigen detected by FMC7 is not identical with any of the conventional B cell markers, including surface membrane IgM, C3 receptors, Fc receptors, and the binding site for mouse erythrocytes. Another monoclonal antibody, FMC1, which reacts specifically with B lymphocytes, binds a separate antigenic determinant. Thus, FMC7 appears to recognize a previously undetected marker present specifically on a subpopulation of human B lymphocytes. FMC7 reacts with some but not all B cell leukemias and may have diagnostic applications in leukemia.

Animals↗

PubMed1980

Human lymphocyte markers defined by antibodies derived from somatic cell hybrids. III. A marker defining a subpopulation of lymphocytes which cuts across the normal T-B-null classification.

A somatic cell hybrid line which secreted antibody reacting selectively with a proportion of the white cells in human blood was prepared. The hybridoma appeared to be monoclonal, and the antibody secreted stained 67% of the lymphocyte population in blood. It reacted less well with granulocytes and monocytes. The lymphocytes stained comprised 80% of the T cells and 50% of the B cells. The antibody showed no recognizable pattern in its reactivity with cell lines and leukaemic cells, although B cells tended to react less well than T cells, null cells, or myeloid leukaemic cells. The expression of the antigenic determinant is discussed in relation to the classification of leucocytes. This determinant and certain other markers exhibited differential expression on closely related cells, and yet were shared by more distantly related cells.

Antibodies↗

PubMed1980

Alterations in pentobarbital pharmacokinetics in response to parenteral and enteral alimentation in the rat.

Recent in vitro observations suggest that the intestine, in addition to the liver, may be an important organ of first-pass drug metabolism. While a variety of changes in intestinal morphology and function in response to continuous parenteral and enteral nutrition have been documented, the effect of different routes of alimentation on intestinal drug metabolism has not been previously investigated. Objectives of this study were to assess the contribution of intestinal pentobarbital metabolism to overall in vivo pentobarbital pharmacokinetics in the rat and to determine if differences in pentobarbital pharmacokinetics were seen between parenterally and enterally nourished animals. After 7 days of continuous infusion of amino acid-glucose mixture via a gastric or jugular vein catheter, pharmacokinetic parameters were determined after 40 mg/kg of pentobarbital was given orally or into the portal or femoral vein. Reduced systemic availability of pentobarbital after oral administration as compared to portal vein injection was seen in both alimentation groups indicating that significant intestinal metabolism of pentobarbital occurred in vivo. Total area under the pentobarbital plasma concentration-time curve was significantly greater in parenterally nourished animals as compared with enterally alimented animals after oral, portal vein and systemic vein drug administration. Differences in pentobarbital, pharmacokinetics between the two alimentation groups appeared to be primarly due to effects on hepatic pentobarbital metabolism. While the mechanism producing these changes has not been defined, differences in gut hormones release and/or pancreatic secretion in response to the two routes of alimentation may be contributory. The widespread use of enteral and parenteral alimentation in clinical medicine suggests that studies to determine if nutrition route of administration similarly influences drug metabolism in humans may be indicated.

Administration, Oral↗

PubMed1980

Human lymphocyte markers defined by antibodies derived from somatic cell hybrids. I. A hybridoma secreting antibody against a marker specific for human B lymphocytes.

A hybridoma has been isolated from the products of fusion of a myeloma cell line with spleen cells from mice immunized with a human B cell line. After cloning, the hybridoma secretes antibody with the following properties: (i) Human B-lymphoblastoid cell lines react with the antibody while T and null cell lines do not. (ii) The antibody reacts with the majority of leucocytes in the blood of patients with CLL, but with a minority of cells in the blood of patients with AML or ALL of the null or T type. (iii) The antibody reacts with 9-21% of mononuclear cells in normal peripheral blood. The reacting cells are not T cells and overlap extensively with cells identified as B cells by other markers. The antigen identified by this antibody appears to be distinct from known B cell markers, and is put forward as a new B cell marker with diagnostic potential.

Animals↗

PubMed1980

Human lymphocyte markers defined by antibodies derived from somatic cell hybrids. II. A hybridoma secreting antibody against an antigen expressed by human B and null lymphocytes.

A hybridoma (FMC4) has been derived which secretes antibody showing selective reaction with human B lymphocytes, monocytes and some null lymphocytes. Few, if any, T lymphocytes in normal blood are stained, although stimulation of lymphocytes with PHA leads to an increase in the proportion of cells reacting with the hybridoma antibody. The antibody reacts with B and null lymphoblastoid cell lines but not with T cell lines. B chronic lymphocytic leukaemia (CLL) cells but not T-CLLs are stained and null-type acute lymphoblastic leukaemia (ALL) cells but not T-type ALL also react. Normal blood myeloid cells do not react with FMC4 supernatant whilst some myeloid leukaemias do. The expression of the antigen reacting with FMC4 supernatant suggests that FMC4 may secrete an antibody against the human equivalent of the Ia antigen.

Antibodies↗

PubMed1980

Alterations in pentobarbital and meperidine pharmacokinetics induced by bile duct ligation in the rat.

Although impaired microsomal drug metabolism has been demonstrated in response to bile duct ligation, there has been little previous assessment of the effects of extrahepatic biliary obstruction on drug pharmacokinetics in vivo. In this study, the effects of bile duct ligation on overall disposition on pentobarbital and meperidine in the rat have been assessed in vivo and in isolated perfused rat livers. A significant reduction in clearance of both compounds was seen in response to bile duct ligation. No change in protein binding of either drug was demonstrated, but alterations in initial volume of distribution of both drugs occurred in response to extrahepatic biliary tract obstruction. A significant reduction in the rate of perfusate flow was also seen in perfused liver experiments using livers from animals with previous bile duct ligation. Reduction in clearance of both a high extraction drug (meperidine) and a lower extraction drug (pentobrbital) in response to bile duct ligation suggests that both hepatic blood flow and drug metabolizing enzyme activity may be altered by extrahepatic biliary tract obstruction.

Animals↗