Biomedical subjects

F R Davey

Publications and source records attributed to F R Davey.

At least 55 records · Page 3Linked to original sources

PubMed1989

A polyclonal CD4+ and CD8+ lymphocytosis in a patient doubly infected with HTLV-I and HIV-1: a clinical and molecular analysis.

HTLV-I is associated with adult T-cell leukemia/lymphoma (ATL) characterized by monoclonal expansions of CD4+ T-lymphocytes. In this report we describe a histologically benign, polyclonal HTLV-I infection in a patient exhibiting both an absolute CD4+ and CD8+ lymphocytosis. Three T-cell lines containing integrated HTLV-I proviral copies established from this patient were initially polyclonal, but with time all grew out the same two clones as determined by analysis of their T-cell antigen receptor beta chain gene rearrangements. The patient subsequently developed pulmonary and nasopharyngeal nodules containing HTLV-I infected cells. Restriction analysis of the patient's HTLV-I provirus revealed no differences from prototype HTLV-I and the tax gene was normally expressed in vivo and in vitro. The patient's T-lymphocytosis and HTLV-I+ pulmonary tract nodules were put into a complete clinical remission by treatment with alkylating agents and steroids. Subsequently, the patient developed a severe immunodeficiency state and expired. Retrospective serologic and gene amplification assays for HIV-1 demonstrated that he had been doubly infected from the time of presentation. Postmortem analysis by polymerase chain reaction revealed the presence of both HTLV-I and HIV-1 in lymphatic tissues and the testes; HIV-1 was also detected in brain tissue.

Acquired Immunodeficiency Syndrome↗

PubMed1989

Morphologic and cytochemical characteristics of acute promyelocytic leukemia.

The existence of two distinct subtypes of acute promyelocytic leukemia was confirmed and characterized based on morphologic features of leukemic cells in a series of 63 patients studied by the Cancer and Leukemia Group B (CALGB). Seventeen patients (27%) had microgranular leukemic cells (M3V), and 46 patients (73%) had hypergranular leukemic cells (M3). These patient cohorts were studied for other laboratory and clinical features. Leukemic cells from M3V patients stained less frequently than leukemic cells from M3 patients for myeloperoxidase (median, 93% vs. 99%; P = .006), periodic acid-Schiff (median, 57% vs. 92%; P = .0001), ASD-chloroacetate esterase (median, 45% vs. 87%; P less than .0001), and alpha-naphthyl acetate esterase (0% vs. 37%; P = .0003). Patients with M3V had a higher platelet count (median, 50 vs. 30 x 10(9)/L; P = .01) and tended to have a higher leukocyte count (median, 7.4 vs. 2.2 x 10(9)/L; P = .06) than M3 patients. The patients with M3V morphology were more likely to be nonwhite (29% vs. 7%; P = .03), female (71% vs. 37%; P = .02), and to be infected at the time of presentation (71% vs. 35%; P = .02). No differences in the frequency of the t(15;17) karyotype or the immunophenotypic expression of the leukemic cells were noted in the two morphologic subtypes of acute promyelocytic leukemia. Fewer patients with M3V tended to enter complete remission (65% vs. 80%; P = .20), but no significant differences were found in the duration of complete remission (P = .81; 1 year rate, 50% vs. 85%), or probability of survival (P = .67; 1 year rate, 49% vs. 68%).

Adolescent↗

PubMed1989

Factors in the liquid portion of stored blood inhibit the proliferative response in mixed lymphocyte cultures.

The transfusion of blood may suppress the immune responses of patients with renal transplants and with malignant disorders. To study the in vitro suppressive effects of banked blood, 4 units of blood were stored in CPDA-1 and ADSOL at 4 degrees C for 14 days. Lymphocytes and plasma or ADSOL supernatants were harvested on Days 0, 4, 7, 10, and 14. Subpopulations of lymphocytes were enumerated by flow cytometry. Recalcified and heat-treated plasma and supernatants from the units of blood were added to mixed lymphocyte cultures (MLC) composed of cells from normal individuals. No significant changes were noted in the proportions of T or B cells from blood stored under these conditions. A 60 +/- 3 percent inhibition in the proliferative response was observed when plasma from CPDA-1 units was added to MLCs (p less than 0.02). Supernatants from ADSOL units demonstrated a 29 +/- 4 percent inhibition (p less than 0.10) of the proliferative response, and this inhibition of response was observed on all 14 days of the study. When appropriate concentrations of dextrose or adenine were added to other MLCs, adenine (at the concentration found in ADSOL) caused a significant inhibition of the proliferative response. This inhibition was not, however, as marked as that observed with recalcified, heat-treated plasma from CPDA-1 units. We conclude that adenine plus some additional factor(s) found in the liquid portion of stored blood inhibits the proliferative response of normal lymphocytes. It is possible that these factors contribute to the immune suppression observed in vivo in some patients who receive blood transfusions.

Adenine↗

PubMed1988

Abnormal neutrophils in acute myeloid leukemia and myelodysplastic syndrome.

Neutrophils and band forms from patients with acute myeloid leukemia and myelodysplastic syndrome were stained for the presence of myeloperoxidase using a cytochemical method (diaminobenzidine/hydrogen peroxide) and the alkaline phosphatase--anti-alkaline phosphatase immunocytochemical procedure (using monoclonal anti-myeloperoxidase). Neutrophils and bands were also stained for elastase and lactoferrin using monoclonal and polyclonal antibodies, respectively. Subpopulations of neutrophils and bands from cases of acute myeloid leukemia and myelodysplasia exhibited a qualitative and/or quantitative deficiency in myeloperoxidase. In addition, a quantitative decrease in elastase and/or lactoferrin staining was detected. Thus, neutrophils and bands from patients with acute myeloid leukemia and myelodysplastic syndrome have a defect in one or more of the constituents of primary and/or secondary granules. These defects are consistent with the view that abnormal neutrophils and bands are derived from a malignant clone of myeloid precursor cells.

Cytoplasmic Granules↗

PubMed1988

The use of monoclonal antibody Y1/82A in the identification of acute myeloblastic and monocytic leukemias.

A newly developed monoclonal antibody (Y1/82A), which binds a cytoplasmic antigen in peripheral blood monocytes and tissue macrophages, was tested for its ability to detect monocytic differentiation in acute myeloid leukemia, i.e., to distinguish French-American-British (FAB) groups M4 and M5 from FAB groups M1, M2, M3, M6 and M7. Staining was performed by the alkaline phosphatase-antialkaline phosphatase (APAAP) immunocytochemical technic on bone marrow smears from 29 cases of acute myeloid leukemia, on 17 normal peripheral blood and/or bone marrow smears, on bone marrows from 10 cases of lymphoid leukemia, and on lymph nodes of 13 patients with lymphoma. Neoplastic cells from 11 of 11 patients with either M4 or M5 leukemia had positive results, whereas only 2 out of 18 cases of M1, M2, M3, M6, and M7 leukemia had positive results. In normal samples, only peripheral blood monocytes, bone marrow macrophages, and megakaryocytes stained. Lymphoid neoplasms were unreactive. These results suggest that monoclonal antibody Y1/82A may be a useful reagent in detecting cases of M4 and M5 acute myeloid leukemia and that it offers a valuable alternative to nonspecific esterase cytochemistry.

Antibodies, Monoclonal↗

PubMed1988

The immunophenotyping of extramedullary myeloid cell tumors in paraffin-embedded tissue sections.

Extramedullary tissue infiltrates of acute myeloid leukemia are rare and often difficult to recognize in routine paraffin-embedded tissue sections. Since appropriate therapy for these tumors depends on their precise identification, we have studied a series of tissues infiltrated with primitive myeloid cells using monoclonal and polyclonal antibodies capable of labeling cells of the myeloid/monocytic system in paraffin-embedded tissue sections. The current retrospective study involved tissues from 15 patients (eight men and seven women) with a mean age of 51 years (range, 23-77). A diagnosis of extramedullary myeloid cell tumors had been made on the basis of routine histology, chloroacetate esterase cytochemical stain, and--in some cases--electron microscopy. Paraffin-embedded tissue sections were cut and stained employing the alkaline phosphatase antialkaline phosphatase (APAAP) immunocytochemical procedure with monoclonal antibodies against leukocyte-common antigen (PD7/26-2B11), restricted components of the leukocyte-common antigen (UCHL1, 4KB5), granulocytes (Mac-387, Leu-M1), leukocytes (MT1, MT2, LN1, LN2), HLA-DR (LN3), and elastase (NP57), as well as polyclonal antibodies against lactoferrin, lysozyme, alpha-1-antitrypsin, and alpha-1-antichymotrypsin. Results indicate that antibodies against Mac-387, elastase, and lysozyme are most useful in the recognition of neoplastic myeloid cells. We conclude that tissues containing granulocytic tumors can be identified in paraffin-embedded tissue sections using a panel of antibodies and the APAAP procedure.

Adult↗

PubMed1988

Antisera against epitopes resistant to denaturation on T3 (CD3) antigen can detect reactive and neoplastic T cells in paraffin embedded tissue biopsy specimens.

Polyclonal rat antisera, raised against affinity purified CD3 antigen, gave strong immunoenzymatic labelling of T cells in routine paraffin embedded sections, with negligible background staining. The specificity of these reactions was confirmed by staining biopsy specimens from 21 previously phenotyped non-Hodgkin's lymphomas (including 14 of T cell origin and six of B cell origin). It is suggested that the ability of the polyclonal anti-CD3 antisera to detect T cells in paraffin sections is due to the presence in these sera of antibodies against fixation resistant epitopes on CD3 antigen, and that immunisation with purified denatured preparations of other white cell associated antigens may broaden the range of antibodies suitable for the phenotypic analysis of leucocytes in routine histological samples.

Antigens, Differentiation, T-Lymphocyte↗

PubMed1988

Monoclonal antibody (Y1/82A) with specificity towards peripheral blood monocytes and tissue macrophages.

A new monoclonal antibody, Y1/82A, was raised against phytohaemagglutinin activated peripheral blood mononuclear cells. Using an immunohistochemical technique it was shown that Y1/82A reacts against peripheral blood and bone marrow monocytes and resident macrophages from essentially all human tissues. Y1/82A bound to determinants present in leukaemic cells from patients with acute myelomonocytic leukaemia and acute monocytic leukaemia, but not to neoplastic cells from patients with malignant lymphoproliferative disorders or malignant epithelial tumours. Y1/82A failed to react with other cell types, with the exception of osteoclasts and megakaryocytes. Analysis by Western blotting showed that the antigen detected by antibody Y1/82A was associated with intracellular granules in macrophages. Monoclonal antibody Y1/82A may be useful in the diagnosis of monocytic leukaemias and histiocytic neoplasms and in the identification of macrophages in tissues from various inflammatory and neoplastic conditions.

Antibodies, Monoclonal↗

PubMed1988

Morphologic and cytochemical characterization of adult lymphoid leukemias which express myeloid antigen.

Cancer and Leukemia Group B demonstrated that adults with acute lymphoid leukemia (ALL) possessing blast cells with myeloid antigens (My+ALL), as identified by monoclonal antibodies against CD13 and CD33, have a worse prognosis than those lacking myeloid antigens (My-ALL). Consequently, we further studied this group of adults with ALL to determine if these immunological groups could be distinguished by morphological and cytochemical criteria. Bone marrow films were classified according to French-American-British Co-operative Group Criteria, assessed for myelodysplasia, and examined for blasts with azurophilic granules. More cases of My+ALL had L2 morphology than did My-ALL (68% vs. 49%, p = 0.04), and more cases of My+ALL were positive for acid alpha-naphthyl acetate esterase (61% vs. 31%, p = 0.03). The presence of myelodysplastic changes was not significantly different in My+ALL (13%) as compared to My-ALL (5%), but more cases of My+ALL had unusual blasts (monocytoid features and cytoplasmic buds) than did My-ALL (19% vs. 0%, p less than 0.01). In addition, more cases of My+ALL had greater than 5% of the blasts with azurophilic granules (42% vs. 13%, p = 0.01). In the My+ALL group the presence of azurophilic granules was associated with a longer median survival (13.5 months vs. 1.5 months, p less than 0.01). We conclude that My+ALL can be suspected when cases possess L2 morphology, unusual blasts, positive staining for acid alpha-naphthyl acetate esterase, and greater than 5% azurophilic granules. In addition, the poor risk group (My+ALL) can be further subdivided into better and poorer risk subgroups based on the presence of azurophilic granules.

Adolescent↗

PubMed1988

The T-lymphocyte colony-forming cell (T-CFC): in vitro studies of progenitors and progeny.

The lineage of T-lymphocyte colony-forming cells (T-CFC) and the phenotype of the progeny of T-CFC have not yet been well-defined. To characterize the progenitor cells and progeny of the T-CFC, we separated normal human peripheral blood lymphocytes into enriched lymphocyte subpopulations, stimulated with various mitogens and cultured in a semisolid agar system. After 5 days, the number of colonies was counted, and the presence of CD4+ and CD8+ cells was determined in situ with FITC-conjugated monoclonal antibodies. Plating of B cells provided the lowest, T cells an intermediate and null cells the highest number of T-cell colonies (P less than 0.05). CD4+ and CD8+ cells produced equivalent numbers of T-cell colonies. T-cell colonies consisted of either CD4+ or CD8+ cells; mixed-cell colonies were rarely present. Plating of CD4+ or CD8+ cells produced both CD4+ and CD8+ colonies. We conclude that T-CFC exist in the CD4+, CD8+ and null-cell populations. In addition, T-CFC give rise to T-cell colonies possessing either CD4+ or CD8+ determinants.

B-Lymphocytes↗

PubMed1988

Use of the APAAP method in the classification and diagnosis of hematologic disorders.

The APAAP technique is a sensitive and relatively easy immunocytochemical method to perform. It requires only a modest amount of laboratory space and no expensive equipment with the exception of a light microscope. Staining can be performed on peripheral blood and bone marrow films as well as cryostat and paraffin-embedded tissue sections. Prior to staining peripheral blood and bone marrow films as well as cryostat sections, slides can be stored at -70 degrees C, thus allowing for batch processing of specimens. Stained slides can be kept at room temperature for prolonged periods of time without loss of label. Surface or cytoplasmic determinants can be stained with the APAAP method. Because the preparations are usually counterstained, the identification of the labeled cells can be observed and photographed. The APAAP method is a reliable procedure and a significant addition to the routine hematology and histopathology laboratory.

Alkaline Phosphatase↗

PubMed1988

Lymphocytic surface markers in lymphoid leukemoid reactions.

Although mononuclear cell surface markers are primarily used to determine the lineage and stage of differentiation of leukemias and lymphomas, they can also be helpful in discriminating between some cases of neoplastic and reactive conditions. Peripheral blood lymphocytosis secondary to infection most often shows increased numbers of activated T cells of the suppressor/cytotoxic subset. A few exceptions, such as in pertussis, show predominantly T-helper cells. Although persistent B-cell lymphocytosis is most often associated with neoplastic conditions, B-cell predominant reactive conditions may also occur. Lack of light chain restrictions on B-cell membranes suggests non-neoplastic disorders. Reactive lymphadenopathy most often shows a predominance of T cells with normal to increased T-helper/T-suppressor cell ratios. In addition, normal ratios of kappa/lambda light chain surface immunoglobulin usually occur on B cells of reactive lymph nodes. Benign lymphocytic infiltrates in skin most often show a predominance of activated T-helper cells. Distinguishing reactive from neoplastic dermal infiltrates by mononuclear cell markers can be extremely difficult and may require DNA genotypic analysis. Mononuclear cell markers applied to bone marrow in patients treated for leukemia and other disorders must also be interpreted with caution. The presence of CD10 antigen (CALLA) may herald recurrence of leukemia; however, this determinant is not leukemia-specific and may be found on normal cells. Similarly, lymphoid cells bearing TdT often represent recurrent leukemia, and they must be differentiated from immature nonmalignant TdT-positive cells. Immunologic surface markers must be interpreted together with a careful review of the morphology of the tissues.(ABSTRACT TRUNCATED AT 250 WORDS)

Antigens, Differentiation, B-Lymphocyte↗

PubMed1987

Quantitative assay of human T-cell leukemia/lymphoma virus transformation.

The in vitro transformation of normal T-lymphocytes by human T-cell leukemia/lymphoma virus (HTLV-I) is possible utilizing cocultivation techniques. We now report on a quantitative assay for HTLV-I transformation. Transformed cell lines were produced by cocultivation of either preactivated (phytohemagglutinin and T-cell growth factor) or nonactivated peripheral blood mononuclear cells with an equal number of lethally irradiated HTLV-I-positive donor cells (MT-2). After 14 days in liquid culture, transformed cells were plated in a 2-layer soft agarose system with or without T-cell growth factor (TCGF). Colony formation among 50 normal controls was observed at varying efficiencies with a mean number of 179 colonies (range, 6-599) in the presence of TCGF (up to a 2-log difference). The day 14 T-cell cultures demonstrated relatively low colony-forming efficiencies (less than or equal to 0.1%) and enhanced colony formation in the presence of TCGF. Day 14 after cocultivation was chosen for this assay based on a dose-response relationship between colony formation and the virus-positive donor cell inoculum and the known kinetics of colony growth of normal activated T-cells. An analysis of individual colonies indicated that they were of target cell origin and HTLV-I positive. Recombinant beta-interferon in increasing concentrations caused a decrease in colony formation as measured in this assay. Long-term cell cultures (2-18 months) showed higher colony-forming efficiencies (up to 1.0%) which were not enhanced by TCGF. The ability to quantitatively evaluate transformation via colony counts will provide an opportunity to study differences in transforming efficiencies attributable to varying target cells, donor cells, or blocking factors such as interferons, drugs, or anti-HTLV-I antibodies.

Cell Line↗

PubMed1987

Clinical importance of myeloid antigen expression in adult acute lymphoblastic leukemia.

To determine the clinical importance of immunophenotypes in adult acute lymphoblastic leukemia (ALL), we prospectively studied 76 patients with this condition. Before treatment, lymphoblasts were tested for reactivity with monoclonal antibodies to B-cell, T-cell, and myeloid (My) antigens. Unexpectedly, myeloid antigens (MCS-2 or MY9) were identified in 25 patients (33 percent), usually in conjunction with B-cell or T-cell antigens. Among My+ patients, 15 (60 percent) expressed B-cell antigens (B+T-My+); all 6 tested had rearranged immunoglobulin genes. Five patients (20 percent) expressed T-cell antigens (B-T+My+), and one My+ patient expressed both B-cell and T-cell antigens. Only myeloid antigens (B-T-My+) were expressed in four patients (16 percent); three who were tested had germ-line immunoglobulin and T-cell-receptor gene configurations. Although no significant differences in presenting clinical features were found, My+ patients had fewer complete remissions than My- patients (35 vs. 76 percent, P less than 0.01). No differences in response or survival were observed between My+ and My- patients expressing T-cell antigens. However, among those expressing B-cell antigens, My+ patients had fewer complete remissions (29 vs. 71 percent, P = 0.02) and shorter survival (P = 0.03; median, 8.1 vs. greater than 26 months). These findings indicate that expression of myeloid antigen identifies a high-risk group of patients with adult ALL for whom alternative forms of treatment should be investigated.

Adult↗

PubMed1987

Impaired synthesis of immunoglobulin in patients with chronic lymphocytic leukemia.

The cause of hypogammaglobulinemia in patients with chronic lymphocytic leukemia (CLL) is unknown. Experiments were performed to determine if sera, monocytes, or non-T cells from patients with CLL suppress the proliferative response and synthesis of immunoglobulin (Ig) following incubation with pokeweed mitogen (PWM) in cocultures with lymphocytes from normal individuals. The data indicate that sera and monocytes from patients with CLL did not suppress the proliferative response or synthesis of Ig normal non-T cells. When various numbers of normal non-T cells and CLL non-T cells were cocultured with a constant number of normal T cells, the proliferative response and the concentration of supernatant Ig decreased as the proportion of CLL non-T cells increased. Since similar results were obtained when irradiated non-T cells from normal individuals were substituted for non-T cells from patients with CLL, we believe that the decrease in proliferative response and diminished synthesis of Ig is not the result of the suppressor non-T cells but is related to the dilution of normal B cells by inert non-T cells. We conclude that these experiments serve as as in vitro model for patients with CLL and suggest that the hypogammaglobulinemia observed in this disease is related to the diluting out of normal B cells by the accumulation of neoplastic B cells in the peripheral blood, bone marrow, and lymphoid tissue of these patients.

Adult↗

PubMed1987

Serum from patients with non-Hodgkin's lymphoma (NHL) inhibits T-cell colony formation.

This study compared T-cell colony formation in soft agar of lymphocytes from the peripheral blood and lymph nodes of patients with non-Hodgkin's lymphoma (NHL) with T-cell colony formation of peripheral blood lymphocytes from normal individuals. Mononuclear cells were separated from other blood and lymph node elements on density gradient columns, phenotyped for T- and B-cell antigens using monoclonal antibodies, and then plated in soft agar cultures. Lymphocytes from peripheral blood and lymph nodes of patients with NHL exhibited less T-cell colony formation (p less than 0.01) than did lymphocytes from normal individuals. This decrease in T-cell colony formation was not the result of the number of T cells or null cells plated, or differences in proportions of T helper and T suppressor cells. However, when sera from patients with NHL were incubated with normal lymphocytes before plating in soft agar, a decrease in number of T-cell colonies was observed (p less than 0.01). We conclude that peripheral blood and lymph node mononuclear cells from patients with NHL have a decreased ability to form T-cell colonies in soft agar cultures and that this decrease is related, at least in part, to the presence of serum factor(s).

Agar↗

PubMed1987

Immunophenotyping of acute myeloid leukemia by immuno-alkaline phosphatase (APAAP) labeling with a panel of antibodies.

A panel of eight antibodies was used by the alkaline-phosphatase/anti-alkaline phosphatase (APAAP) method to stain peripheral blood films, bone marrow smears, and cytocentrifuge preparations from 29 cases of acute myeloid leukemia. These findings were correlated with the French-American-British (FAB) classification. Leukemic cells from six cases of myeloblastic leukemia (FAB;M1) were predominantly labeled by the antimyeloperoxidase monoclonal antibody (MPO-7). Leukemic cells from the majority of eight cases of myeloblastic leukemia with maturation (FAB;M2) and progranulocytic leukemia (FAB;M3) stained with monoclonal antibodies MPO-7, NP57 (anti-elastase), and EBM11 (antimonocyte/macrophage). Leukemic cells from six cases of myelomonocytic (FAB;M4) and five cases of monocytic (FAB;M5) leukemia were most often labeled with antibodies MPO-7, NP57, and EBM11 as well as monoclonal antibodies Y1/82A (anti-monocyte) and KB90 (against the p150, 95 molecule, CD11c; a monocyte/granulocyte marker), but not with monoclonal antibody C17 (antiglycoprotein IIb/IIIa) and/or monoclonal antibody Y2/51 (antiglycoprotein IIIa). Erythroblasts from a single case of erythroleukemia (FAB;M6) were not labeled with any of the antibodies from this panel. Leukemic cells from two cases of acute megakaryocytic leukemia (FAB;M7) stained strongly with the monoclonal antiglycoprotein IIIa/IIb antibody (C17) and antiglycoprotein IIIa antibody (Y2/51). Staining by the APAAP method with this panel of antibodies was easy to perform, required no expensive instrumentation, and provided useful information in the classification of acute myeloid leukemia.

Alkaline Phosphatase↗

PubMed1987

Localized conjunctival amyloidosis associated with extranodal lymphoma.

A 62-year-old man was found to have a large asymptomatic amyloid nodule of the conjunctiva. Within the next year, a diffuse mixed small and large cell lymphoma of his scapula developed with amyloid in its stroma. No abnormal serum or urine protein was found. Subsequently, rib and paraspinal masses appeared. After irradiation and chemotherapy, the patient died of bronchopneumonia, 3 years after onset. By immunostaining, the amyloid of both conjunctiva and scapular tumor was of polyclonal immunoglobulin (AL) type, most prominently IgG and lambda chains, with lesser staining for IgA and kappa chains. The tumor cells showed a similar pattern. To our knowledge, this is the first report of systemic lymphoma and localized conjunctival amyloidosis without a serum paraprotein, and the first such association with a lymphoma of this cell type. Immunotyping of conjunctival amyloidosis should be performed to guide the workup for possible systemic disease.

Amyloidosis↗