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Biomedical subjects

D C Linch

Publications and source records attributed to D C Linch.

At least 253 records · Page 14Linked to original sources
PubMed1985

Bone marrow T cell colony-forming cells: studies of their origin and use in monitoring T cell-depleted bone marrow grafts.

Peripheral blood T cell colony forming cells (T-CFC) are mature T cells. When blood was fractionated into sheep red blood cell receptor positive (E+) and negative (E-) fractions, T cell colony growth was largely restricted to the E+ population. When bone marrow was similarly fractionated, many colonies grew from the E- cells but myeloid colonies also grew making interpretation of colony numbers difficult. We have, therefore, also assessed T cell proliferation during culture as an expansion index (EI) by determining the absolute number of T cells pre and post culture. This data shows that T cell expansion is on average nine times greater in the E- marrow fraction than in the E+ fraction. Studies are presented suggesting that this is because marrow E- cells contain appropriate accessory cells and that high numbers of T cells inhibit T cell growth. The cells giving rise to bone marrow T cell colonies thus appear to be contaminating mature T cells rather than pre-thymic progenitor cells. We have measured T cell expansion in culture as a sensitive assay of T cell contamination following procedures to remove T cells from bone marrow grafts for the prevention of graft versus host disease (GVHD).

Bone Marrow↗
PubMed1984

The effect of mitogenic lectins and monoclonal antibodies on intracellular free calcium concentration in human T-lymphocytes.

The effect of mitogenic lectins and the mitogenic antibody UCHT1 on the cytoplasmic free Ca2+ concentration ( [Ca2+]i) in human lymphocytes was investigated by using the fluorescent Ca2+-indicator quin2 . Phytohaemagglutinin, concanavalin A and UCHT1 increased [Ca2+]i in T-cells to a maximum level within 2 min. No T-cell response was seen with poke weed mitogen. None of the mitogens affected non-T-cell [Ca2+]i.

Aminoquinolines↗
PubMed1984

Augmentation of fetal-hemoglobin production in anemic monkeys by hydroxyurea.

The increase in fetal-hemoglobin synthesis in patients with beta-thalassemia or sickle-cell anemia induced by 5-azacytidine has been attributed to hypomethylation of DNA in the region of the gamma-globin genes. To determine whether hydroxyurea, a cytotoxic/cytostatic drug that does not influence DNA methylation, might stimulate fetal-hemoglobin synthesis, we phlebotomized two juvenile cynomolgus monkeys to induce anemia and reticulocytosis and then treated them with hydroxyurea. Immediately after phlebotomy was initiated, there was a rise in the level of F cells, which stabilized at an average value of 13 per cent in one animal and 20 per cent in the other during a two-month control period. Fetal hemoglobin gradually rose from undetectable values before bleeding to 3 per cent in one animal and 5 per cent in the other. Sixty-two days after initiation of phlebotomy, hydroxyurea (50 mg per kilogram of body weight per day for five days) induced only a small and transient increase in F cells and fetal hemoglobin. Two weeks later, however, a similar course (100 mg per kilogram per day) resulted in a prompt and dramatic increase in both indexes. These results strongly suggest that S-phase-specific cytotoxic/cytostatic drugs increase fetal hemoglobin by a mechanism that does not involve inhibition of DNA methylation.

Anemia↗
PubMed1984

Unusual T cell proliferations and neutropenia in rheumatoid arthritis: comparison with classical Felty's syndrome.

4 patients are described with rheumatoid arthritis, splenomegaly, neutropenia and an unusual proliferation of T cells in the blood and marrow. These patients are clinically similar to patients with classical Felty's syndrome but can be distinguished from them by staining blood and marrow mononuclear cells with a panel of monoclonal anti-T cell antibodies. The T cells from patients with T cell proliferations stain with UCHT1 (OKT3 equivalent) and UCHT4 (OKT8 equivalent but do not stain with a panel of OKT1-like antibodies. In 7 patients with classical Felty's syndrome there was no increase of UCHT4 cells in the blood and the large majority of T cells stained with OKT1-like antibodies. The marrows from the patients with T cell proliferations contain plentiful haemopoietic progenitor cells and it is probable that the T lymphocytes suppress their normal maturation. There was a poor response to splenectomy in 2 patients with T cell proliferations, and single cytotoxic drug therapy may be more appropriate when therapy is required. The literature is reviewed and it is suggested that the T cell proliferations may be secondary to the rheumatoid process.

Adult↗
PubMed1984

Electrophoretic and cytochemical characterization of alpha-naphthyl acetate esterases in acute myeloid leukemia: relationships with membrane receptor and monocyte-specific antigen expression.

Alpha-naphthyl acetate esterases (ANAE) were examined by cytochemical and isoelectric focusing (IEF) techniques in 48 cases of acute myeloid leukemia that were classified by conventional morphological criteria. Four main types of ANAE isoenzyme patterns were found by IEF, and comparisons with the expression of membrane receptors (Fc-IgG and C3b) and monocyte-specific antigens (UCHM1, UCHALF, and E11) suggest relationships between ANAE isoenzyme synthesis and distinct myeloid maturational stages. The results further indicate that the blast cells of acute myelomonocytic leukemia (AMML) may represent an immature variant of monocytic leukemia (AMoL) and that morphological examination alone is inadequate in the assessment of monocytic differentiation in acute myeloid leukemias. Inhibition studies of cytochemical ANAE activity with sodium fluoride (NaF) show that the presence of NaF-sensitive or NaF-resistant ANAE enzymes is often unrelated to the diagnostic category of acute leukemia. The results of this study are examined in relation to current concepts of myeloid differentiation, and the application of these findings to the subclassification of acute myeloid leukemias is discussed.

Antibodies, Monoclonal↗
PubMed1984

Monoclonal antibodies differentiating between monocytic and nonmonocytic variants of AML.

Blast cells from 70 cases of acute myeloid leukemia (AML), with a preponderance of monocytic variants (M4 and M5), were stained with a panel of 10 monoclonal antibodies (MoAb) that react with normal myeloid cells. Two McAb, UCHMI and UCHALF, stained cells from nearly every case of M4 and M5 leukemia, but not cells from cases of M1/M2 leukemia. Two other antibodies, E11 and UC45, were also specific for the monocytic leukemias, but stained cells from a lesser proportion of cases. The antibodies TG1, OKM1, Smø, DA2, 28, and 5.5 stained a differing proportion of cases in both the M1/M2 and M4/M5 subtypes. Routine morphology and alpha-naphthyl acetate esterase (ANAE) staining were largely in agreement with the antibody findings, though the interpretation of the fluoride sensitivity of ANAE was apparently misleading in 10% of cases. It is concluded that these antibodies, particularly UCHMI and UCHALF, will be of considerable value in the more precise subtyping of AML and that some of this panel of antibodies will be valuable tools for the investigation of normal monocytic differentiation.

Antibodies, Monoclonal↗
PubMed1984

Discordant expression of human Ia-like antigens on hematopoietic progenitor cells.

The expression of HLA-DR, SB, MT2, and DC antigens on human hematopoietic progenitor cells has been determined by using monoclonal antibodies with complement (C)-mediated cell lysis and immune separation techniques. HLA-DR was detected on greater than 85% of CFU-G/M, myeloid clones (MyCl), BFU-E, and CFU-E. CFU-E were less susceptible to C-mediated lysis at suboptimal C concentrations. The polymorphic MT2 and SB antigens were also present on all categories of progenitor cells, although a lesser proportion of cells were positive. Because in most individuals the antigen density of MT2 and SB, as determined by monoclonal antibody staining, was also lower on B cells and monocytes when compared to HLA-DR expression, the lower number of positive progenitor cells probably reflects lower antigen density rather than distinct positive and negative progenitor cell populations. The DC antigen is expressed weakly on monocytes and B cells, although there is considerable individual variation. In some individuals, distinct DC-positive and -negative monocyte populations are detectable. The DC antigen was not detected on myeloid progenitor cells, even in those individuals with moderate DC expression on their monocytes and B cells. This discordant expression of DC and other Ia-like antigens on hematopoietic progenitor cells may be of physiologic significance and may assist in the purification of progenitor cells from blood and marrow.

B-Lymphocytes↗
PubMed1984

Prenatal diagnosis of three cases of severe combined immunodeficiency: severe T cell deficiency during the first half of gestation in fetuses with adenosine deaminase deficiency.

The prenatal diagnosis of severe combined immunodeficiency (SCID) was made in three fetuses by staining fetal blood obtained at fetoscopy with a panel of monoclonal antibodies. There were less than 100 T cells/mm3 of fetal blood in these three cases compared to 2,500/mm3 in 14 immunologically normal fetuses. Cells bearing the cortical thymocyte antigen (NA1/34) were not detected in any of the normal or affected fetal blood samples. Two of the affected fetuses were also homozygous for a deficiency of adenosine deaminase (ADA) with undetectable levels of red cell ADA. All three affected fetuses were aborted and postmortem tissue was obtained in two cases. In both of these cases the thymus was markedly hypoplastic and contained no lymphoid cells. One of these fetuses was homozygous for ADA deficiency and the virtual absence of T cells or thymocytes during the second trimester of pregnancy indicates that placental access to the maternal circulation does not prevent damage to the T lineage stem cells in this disease. Prenatal diagnosis of SCID has previously only been possible in patients with a defined metabolic defect such as ADA deficiency, but these studies indicate that prenatal diagnosis now may be offered for most at risk pregnancies.

Adenosine Deaminase↗
PubMed1983

T cell regeneration after allogeneic and autologous bone marrow transplantation.

Venous blood T cell phenotypes were analysed with monoclonal antibodies after 11 allogeneic and 17 autologous bone marrow transplants. In seven cases studied in the early regenerative period, cells with a thymocyte phenotype were present in the blood. In the large majority of patients treated with both allografts and autografts there was an imbalance of phenotypic 'helper' and 'suppressor' T cell subsets with initially a relative and later an absolute increase of 'suppressor' T cells. This imbalance was still present at over 250 d in eight out nine cases. Suppressor T cells bearing HLA-Dr antigens were abundant in one case of fatal GVHD but not in another, and were also increased following two autografts. It is concluded that T cell phenotyping is not of diagnostic value in sick patients following bone marrow transplantation when graft-versus-host disease is suspected.

Adolescent↗
PubMed1983

Erythropoietin and cord blood haemoglobin in the regulation of human fetal erythropoiesis.

Erythropoietin was estimated by radioimmunoassay in serum from 78 cord blood samples, collected in the second and third trimesters in 72 pregnancies. In 43 samples obtained during or after normal pregnancy (from 19 to 42 weeks gestation) erythropoietin levels increased with gestation. Cord blood haemoglobin also increased with gestation, but the rate of increase was less during the last weeks of pregnancy. Erythropoietin levels were similar in the cord blood of infants of the same gestation, whether born vaginally or by caesarean section. The fetus can respond to severe anaemia or hypoxia with increased erythropoietin levels as early as 24 weeks gestation. Elevated erythropoietin levels were found in two out of eight infants born after labour in which there was 'acute' fetal distress, suggesting the presence of unrecognized chronic fetal hypoxia in these pregnancies.

Blood Transfusion, Intrauterine↗
PubMed1983

Identification of lymphocyte subsets in the newborn using a variety of monoclonal antibodies.

Using a small sample of peripheral venous blood, the normal range for lymphocyte subpopulations (T-cell, B-cell, T-suppressor cell, and T-helper cell) was defined in non-infected preterm and term infants. Lymphocyte subsets were identified using a variety of monoclonal antisera, and analysis was performed using a fluorescent activated cell sorter. Such methods allow an objective assessment of absolute numbers of cells per unit volume of whole blood. There was no significant difference in absolute numbers of lymphocyte subsets between term and preterm appropriate for gestational age (AGA) infants. Infants who were small for gestational age (SGA) had a significant deficiency in absolute numbers of total T-cells, helper and inducer T-lymphocytes, and B-cells compared with both term and preterm AGA infants. All newborn infants (term and preterm; AGA and SGA) had a highly significant increase in absolute numbers of both helper and suppressor T-lymphocytes compared with normal adults.

Antibodies, Monoclonal↗
PubMed1983

Lymphocyte subpopulations in primary immunodeficiency disorders.

Venous blood mononuclear cells from 42 children with primary immunodeficiency disorders and from controls matched for age were studied for lymphocyte subpopulations by E rosetting, surface immunoglobulin, and a panel of anti T cell monoclonal antibodies (OKT series). In 3 cases of severe combined immunodeficiency (SCID) due to adenosine deaminase deficiency, very few circulating T or B cells were found. The other 7 cases of SCID all had normal or, in 3 cases, very high numbers of circulating B cells, but in 6 of these very few cells showed T cell markers. One child had very high numbers of B cells and T cells with an immature pattern of reactivity similar to that found on common thymocytes. In T cell deficient children no consistent pattern was found, but in those with cartilage hair hypoplasia with immunodeficiency there was a low helper (OKT4) to suppressor (OKT8) ratio and high numbers of circulating OKT10 positive cells. In cases of X-linked agammaglobulinaemia circulating B cells were not found but the pattern of T cell markers was normal. In cases of common variable hypogammaglobulinaemia there was a wide scatter of helper (OKT4) to suppressor (OKT8) cell ratios. Five children were studied before and after treatment with the synthetic thymic hormone preparation TP5. There were appreciable alterations in the pattern of staining with anti T cell monoclonal antibodies in 4 of these cases, but in 1 case only was this accompanied by improvements in clinical and immune function.

Agammaglobulinemia↗
PubMed1983

Membrane Fc-IgG and C3b receptors on myeloid leukaemia cells: a comparison with cytoplasmic acid naphthyl acetate esterase cytochemistry.

Membrane receptors for IgG and C3b were examined on blast cells from 57 cases of acute myeloid leukaemia. These acute leukaemias were classified as myeloblastic, myelomonocytic or monocytic following morphological, cytochemical, and immunological investigations. The membrane receptors of leukaemic blast cells appear to be directly related to the degree of monocytic differentiation with the lowest receptor activities found in acute myeloblastic leukaemia. A comparison was also made between receptor and cytoplasmic acid naphthyl acetate esterase (ANAE) activities in 29 morphologically and immunologically-defined myelomonocytic and monocytic leukaemias. This study revealed that the receptor-positive "monocytic component" in a significant proportion of cases showed unexpectedly weak or negative ANAE reactions suggesting a more cautious approach to the interpretation of ANAE cytochemistry in acute leukaemias. The normal development of cytoplasmic ANAE and membrane receptors is also discussed and compared with their abnormal patterns of expression associated with leukaemic transformation.

Carboxylic Ester Hydrolases↗