Hb Fukuyama or alpha 2 beta(2)77(EF1)His----Tyr observed in an Indonesian female.
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Anemia, Hemolytic, Congenital↗
Biomedical subjects
J W Smit
Publications and source records attributed to J W Smit.
Erythroid progenitors in polycythemia vera demonstrate a different response pattern to IL-4 compared to the normal BFU-E from peripheral blood.
Human recombinant interleukin 4 (IL-4) was studied for its effects on erythroid burst-forming units (BFU-E) from normal peripheral blood and from patients with polycythemia vera (PV). IL-4 enhanced the proliferation of normal peripheral blood BFU-E (183% +/- 20% enhancement), whereas in the presence of interleukin 3 (IL-3) no further augmentation was noticed. The IL-4-mediated effects were independent of the absence or presence of adherent cells, B cells, or T cells. These data are in contrast with results obtained from normal human bone marrow cells, in which IL-4 antagonized the enhancing effects of IL-3. In PV a different response pattern was observed. The effects of IL-4 on the erythropoietin (Epo)-independent BFU-E were variable. In five PV patients no suppressive or enhancing effects of IL-4 were observed, whereas in two additional patients a significant decline in the Epo-independent BFU-E was noted. In the presence of IL-3, IL-4 significantly antagonized the IL-3-supported Epo-independent BFU-E in all patients (272% +/- 57% vs 187% +/- 49% enhancement, p less than 0.05). In contrast, IL-4 did not modify the IL-3-supported Epo-dependent BFU-E. In summary, these data suggest a difference between the normal and PV peripheral blood BFU-E. The Epo-dependent erythroid progenitors in PV patients showed a response pattern with IL-3 and IL-4 comparable to that of normal peripheral blood BFU-E, whereas the Epo-independent erythroid progenitors behaved like normal human bone marrow BFU-E, suggesting a shift in the stem cell compartment in PV. This is further supported by the finding that erythroid colony-forming units (CFU-E), normally only present in the bone marrow, could be cultured from the peripheral blood of PV patients in the presence or absence of Epo.
B-Lymphocytes↗
Divergent effects of interleukin-4 (IL-4) on the granulocyte colony-stimulating factor and IL-3-supported myeloid colony formation from normal and leukemic bone marrow cells.
Human recombinant interleukin-4 (IL-4) was studied for its effects on myeloid progenitor cells from normal and leukemic bone marrow cells in the presence and absence of additional growth factors. IL-4 itself did not support myeloid cluster or colony formation (CFU-GM). However, cultures supplied with IL-4 (300 U/mL) and IL-3 demonstrated a significant decline in myeloid colony numbers (CFU-GM) compared with the effects of IL-3 alone: (48 +/- 27 v 88 +/- 27 CFU-GM/10(5) MNC). In contrast, IL-4 augmented the G-CSF-supported CFU-GM: (80 +/- 31 v 148 +/- 52 CFU-GM/10(5) MNC). The effects of IL-4 were not mediated by accessory cells because similar results were obtained with and without T-cell, B-cell, or adherent depleted cell fractions. Morphologic analysis of clusters (day 7) and the colonies (day 14) demonstrated that IL-4 enhanced myeloid colony formation in the presence of G-CSF, whereas the cultures supplied with IL-3 and IL-4 did not show a lineage-restricted decline of CFU-GM. A heterogeneity in growth response was observed in the leukemic counterpart. With the 3H-thymidine proliferation assay, IL-4 augmented the G-CSF-induced proliferation of acute myeloid leukemic (AML) cells in 4 of the 12 cases, while the IL-3-supported proliferation was antagonized in 3 of the 12 cases. In the blast colony assay, IL-4 suppressed the IL-3-supported AML-CFU in the majority of cases, but enhanced the G-CSF stimulated AML-CFU in 3 of 6 cases. These data demonstrate divergent effects of IL-4 on the normal myeloid progenitor cell in the presence of IL-3 or G-CSF, while a variability in responsiveness is observed in the leukemic counterpart.
Bone Marrow Cells↗
Interleukin-4 suppresses the interleukin-3 dependent erythroid colony formation from normal human bone marrow cells.
Human recombinant interleukin 4 (IL-4) was studied for its effects on the erythroid burst forming unit (BFU-E) from human bone marrow cells. IL-4 alone neither supports nor suppresses the erythropoietin (Epo)-dependent colony formation. Different results were obtained when IL-4 was combined with interleukin-3 (IL-3) in the presence of Epo. IL-4 suppressed the IL-3 supported erythroid colony formation in all cases (an increase of 58 +/- 8% with IL-3 versus an increase of 14 +/- 7% with IL-3 plus IL-4, n = 8). This antagonizing effect was dependent on the continuous presence of IL-4 in the culture medium, but was independent of adherent cells, B-, T-cells, or the presence of serum in the culture medium. Finally, the effects of IL-4 and IL-3 were studied on the 'Epo-independent' BFU-E by adding Epo on day 3. A decline of the IL-3 supported BFU-E was observed in the presence of IL-4 but the degree of reduction was equivalent to the results obtained when Epo was supplied at day 0. These findings indicate that IL-4 acts as suppressive growth factor for the IL-3 supported erythroid colony formation from human bone marrow cells.
Bone Marrow Cells↗
Circulating cells in Hodgkin's disease.
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Hodgkin Disease↗
In polycythemia vera human interleukin 3 and granulocyte-macrophage colony-stimulating factor enhance erythroid colony growth in the absence of erythropoietin.
To further define the growth factors required for the in vitro proliferation of erythroid progenitors in polycythemia vera (PV), we have compared the ability of interleukin 3 (IL-3) and granulocyte-macrophage colony-stimulating factor (GM-CSF) to support the growth of erythropoietin (Epo)-dependent and -independent erythroid colony formation. By using nonadherent mononuclear cells from peripheral blood, Epo-dependent colony formation was enhanced by IL-3 and GM-CSF in PV patients. Comparable results were obtained with normal erythroid progenitors. Augmenting effects of IL-3 and GM-CSF were observed on spontaneous erythroid colony formation, i.e., erythroid colony formation in the absence of exogenous supplied Epo. This was not due to a small amount of Epo in the culture media because an anti-Epo antibody did not prevent endogenous colony formation, nor did it prevent the enhancing effects of IL-3. Finally it was observed that in contrast to IL-3, monocyte depletion was required for the enhancing effects of GM-CSF on erythroid colony formation. These results provide evidence that endogenous colony formation in PV is independent of Epo but can be augmented by IL-3 or GM-CSF.
Cells, Cultured↗
Interferon-alpha induction of lymphocytes containing parallel tubular structures.
The induction by IFN-alpha in peripheral blood lymphocytes of parallel tubular structures (PTS) and/or electron-dense granules occurring in a minority of peripheral blood lymphocytes was examined. IFN reportedly augments natural killer (NK) cell activity of large granular lymphocytes (LGL); these cells contain PTS and/or electron-dense granules. Normal peripheral blood mononuclear cells were incubated with IFN-alpha and surface antigen expression was measured by means of indirect immunofluorescence and, at the ultrastructural level, using gold labelled monoclonal antibodies. Surface antigen reactivity with the monoclonal antibodies OKT 3, 4, 8 and Anti-Leu-7 (HNK-1) showed no difference between the IFN-alpha incubation and non-IFN-alpha groups. However, electron microscope investigation revealed significant absolute increases in the percentage of OKT 8+ and Anti-Leu-7+ cells which were PTS-positive after IFN-alpha treatment compared with the control groups. The cytotoxicity assay using the K562 cell line showed enhanced lytic activity. Our results suggest that cells coexpressing the OKT 8 and Leu-7 antigens may be responsible for a minor proportion of the increase in PTS but that IFN-alpha mainly induces PTS and/or associated structures in cells which express the OKT 8+ antigen. These PTS+/OKT 8+ cells may contribute to enhanced cell cytotoxicity.
Antibodies, Monoclonal↗
Gold probe choice in simultaneous detection of human lymphocyte surface antigens at the ultrastructural level.
A double immunogold-labeling method in immunoelectron microscopy was used for simultaneous detection of two antigens by monoclonal antibodies [OKT 8 (CD 8), anti-Leu-7, anti-Leu-11b (CD 16)] on lymphocytes in suspension. The combination of gold probe size (5 nm and 15 nm) and monoclonal antibody was found to be decisive for detecting double-labeled cells with the OKT 8+, Leu-11b+ phenotype. The combinations of OKT 8 labeled with the 5-nm gold probe (OKT 8(5] and anti-Leu-11b with the 15-nm gold probe (Leu-11b15) gave double-labeled cells; the reverse situation, using OKT 8 with a 15-nm gold probe (OKT 8(15] and anti-Leu-11b with a 5-nm gold probe (Leu-11b5), did not. Double-labeled OKT 8+, Leu-7+ cells were detected irrespective of which gold probe combination was applied. Our findings indicate that although the double immunogold-labeling method is well suited for study of lymphocyte subsets, it is important to determine suitable combinations of gold probe sizes and monoclonal antibodies for the lymphocyte subset under study, taking into account surface antigen density, so that double labeling ensues.
Antibodies, Monoclonal↗
Method of isolating erythrocytes influences their measured polyamine content.
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Adult↗
K-cell lymphocytosis/neutropenia syndrome: the neutropenia is not caused by autoimmunity.
The role of humoral immune mechanisms in the pathogenesis of the neutropenia in five patients with chronic killer (K)-cell lymphocytosis was studied. For the detection of neutrophil antibodies in the patient's blood, immunofluorescence, cytotoxicity and agglutination tests and a sensitive antibody-dependent cellular cytotoxicity (ADCC) assay were applied. An assay for bone-marrow colony growth (CFU-GM, BFU-E) inhibition was applied as well. A C1q-binding test was used to detect immune complexes. The lymphocytes of all five patients had the capacity to lyse alloantibody sensitized neutrophils. Neutrophil-bound IgG was found only in one patient. Two patients had neutrophil-reactive antibodies in their serum; in one patient these antibodies were only detectable in the ADCC using the patient's serum to sensitize target cells. However, these antibodies reacted also with lymphocytes, were absorbable with platelets and thus probably were HLA antibodies. The serum of one of these two patients showed complement-dependent CFU-GM and BFU-E inhibition, but the observed inhibition was probably also due to the anti-HLA antibodies present in his serum, as the inhibiting effect disappeared after absorption of the serum with platelets. The serum of only one patient contained low amounts of immune complexes, as measured in the C1q-binding test. Our data suggest that humoral autoimmune mechanisms, such as autoantibodies against neutrophils or neutrophil precursors or circulating immune complexes, do not seem to play an important role in the K-cell lymphocytosis/neutropenia syndrome. The possible role of the expanded K-cell population, and its humoral products (tumour necrosis factor, interferons), in the syndrome is discussed.
Aged↗
T cells in patients with chronic T gamma lymphocytosis: morphology, cytochemistry, ultrastructure and immunological characteristics.
We have studied the morphology and cytochemistry in relation to the immunological phenotyping and functional properties of T cells from eight patients with chronic T gamma lymphocytosis. At the light microscopic level the morphology of the patients' lymphocytes was similar to that described for large granular lymphocytes. Ultrastructurally, a division into two groups could be made on differences in the amount of cytoplasm and the location and the more irregular form of the nuclei. The lymphocytes of one group (five patients) had in common the phenotype Fc gamma +, T3 +, T4 -, T8 +, Ia -, M1 - and demonstrated (with the exception of one patient) the same functions: presence of K-cell activity, absence of NK, helper and suppressor cell activities. In the other group (three patients), the lymphocytes of one patient showed the same phenotype and functions as those indicated above. The other two patients both lacked the T8 antigen on their lymphocytes but were different with regard to other surface markers. In addition, their cells were functionally identical: both demonstrated NK- and K-cell activity. Thus in this group of eight patients with chronic T gamma lymphocytosis, the immunological and functional subdivision paralleled in part a morphological division at the ultrastructural level.
Acid Phosphatase↗
T gamma lymphocytosis is clinically non-progressive but immunologically heterogeneous.
Immunological studies were performed with the expanded T gamma cells of five patients with T gamma lymphocytosis. All patients showed a stable clinical picture with persistent T gamma lymphocytosis and neutropenia, with or without recurrent infections. The expanded T gamma cells in the blood had the T1-3+4-8+11+M1- phenotype, with the exception of one patient whose cells lacked the T8 marker. The expanded T gamma cell population did not proliferate in response to T cell mitogens and did not show immunoregulatory activity on pokeweed mitogen driven immunoglobulin synthesis. In four of the five patients the T gamma cells had killer cell activity against IgG sensitized mouse mastocytoma cells. Taken together, these results and the data from the literature, it is concluded that T gamma lymphocytosis represents a spectrum of T cell expansions clearly distinct from clinically progressive mature T cell neoplasias.
Aged↗
Effect of sera from patients with Hodgkin's disease on normal donor lymphocytes containing parallel tubular structures.
Normal donor peripheral blood mononuclear cells incubated for 24 h with sera from patients with Hodgkin's disease were investigated by electron microscopy for the presence of parallel tubular structures (PTS) and/or amorphous electrondense granules (large granular lymphocytes = LGL). In comparison with normal human serum, 14 out of 29 sera of the patients induced a marked increase in the percentage of LGL. From a limited number of experiments it was likely that this increase is paralleled by an increase in Fcgamma receptor-bearing cells after the incubation. This serum effect did not show a correlation with the number of Fcgamma receptor-positive lymphocytes in the peripheral blood of the patients. A difference in the induction effect could be demonstrated between the sera from patients with a favourable and those with an unfavourable clinical course, but this distinction was not absolute. The presence or absence of splenic involvement by Hodgkin's disease does not apparently influence the effect of the sera. From experiments using sera positive for immune complexes or anti-Epstein-Barr virus antibodies, it seems unlikely that these factors are responsible for the observed increase in LGL.
Antibody-Dependent Cell Cytotoxicity↗
Successful chemotherapy with deoxycoformycin in adult T-cell lymphoma-leukaemia.
A patient from the Caribbean area with active T-cell lymphoma-leukaemia was primarily treated with deoxycoformycin (DCF), 5 mg/m2 i.v. on 3 consecutive days, followed by 5 mg/m2 i.v. weekly. A complete remission was attained and maintained during several weeks with DCF. A single consolidation course with other cytostatics was then given. The patient continues in complete remission without further therapy, 24 months after diagnosis, 17 months after the last cytostatic drugs. T-cell lymphoma-leukaemia has a bad prognosis with conventional anti-lymphoma therapy but was exquisitely sensitive to DCF in this patient.
Adult↗
Functional properties of neoplastic T cells in adult T cell lymphoma/leukemia patients from the Caribbean.
The neoplastic T cells from five patients with adult T cell lymphoma/leukemia (ATLL), born in the Caribbean, were studied with respect to immunoregulatory activity on pokeweed mitogen (PWM) driven immunoglobulin (Ig) synthesis as well as surface-marker phenotypes with monoclonal antibodies. The neoplastic T cells in all patients had an OKT1+4+8-11+M1-I1-3A1- phenotype, but differed in the reactivity with OKT3. None of the patients' cells exerted helper activity on PWM-induced Ig synthesis. The neoplastic cells of three patients had suppressor activity on PWM-induced Ig synthesis. All patients were positive for human T cell leukemia/lymphoma virus (HTLV) or had antibodies against HTLV antigens. It has previously been shown that the neoplastic cells in Japanese ATLL patients and in patients from the Caribbean are indistinguishable by morphology and marker phenotype. We now show them to be also similar with respect to their functional properties.
Adult↗
Susceptibility of the expression of parallel tubular structures in lymphocytes to the exposure to ammonium chloride buffer.
In isolation procedures for lymphocytes, isotonic ammonium chloride buffers are frequently used to lyse erythrocytes. In addition to evidence for an effect on lymphocyte function we now report a morphological alteration after treatment of lymphocytes with ammonium chloride buffer. Expression of parallel tubular structures was lost and only amorphous, electron-dense granules could be observed.
Ammonium Chloride↗
Lymphocytes with parallel tubular structures: morphologically a distinctive subpopulation.
Peripheral blood lymphocytes were fractionated in T, B and Null cell enriched subsets by means of sheep red blood cell rosette (ESRBC) sedimentation and nylon wool adherence. The ultrastructural features of these subpopulation were investigated. The T cell fraction in which the sheep erythrocytes were removed from the ESRBC rosette-forming cells (ESRBC-RFC) by lysis with ammonium chloride, consisted mainly of two morphologically distinctive subsets. The majority of the cells (80%) displayed a smooth surface membrane and had a high nuclear to cytoplasmic ratio with few cytoplasmic organelles. The other cell type (18%) had a relatively rough surface membrane, a low nuclear to cytoplasmic ratio, often an indented nucleus and numerous cytoplasmic organelles such as characteristic amorphous granules and sometimes parallel tubular structures (p.t.s.). If the T cells were obtained after mechanical vibration of the ESRBC-RFC, the majority of these cells appeared morphologically identical to this latter cell type. Cells with p.t.s. and amorphous granules were also demonstrated within the Null and B cell enriched fractions (50% and 25% respectively), though in the B cell enriched fraction this cell type is probably due to a contamination of Null cells. Previous observations had already demonstrated that these cells in the three fractions represent the Fc gamma receptor-bearing lymphocytes. The similarities suggest that the Fc gamma receptor-bearing and p.t.s. containing lymphocytes form a morphologically distinct subpopulation.
Humans↗
Rheumatoid arthritis associated with transient gamma 2-heavy chain disease.
This paper describes the clinical history of a patient (F.-O.) with longstanding rheumatoid arthritis (RA), who subsequently developed a transient gamma 2-heavy chain disease (gamma 2-HCD). Immunochemical studies comprised serial determinations of serum levels of intact IgG, the gamma-HCD protein, IgA, and IgM. New applications of the rocket immunoselection and the radial immunodiffusion were used for the quantitation of the gamma-HCD protein and intact IgG, respectively, in the presence of one another. Immunofluorescent microscopy on bone marrow cells showed cells containing gamma-heavy chains but devoid of light chains. Protein studies of the isolated gamma-HCD protein revealed a molecular weight of 72 000 in the dimeric form, a carbohydrate content of 9.7%, and a PCA-Val-Gln NH2-terminal amino acid sequence. The literature on the rare coexistence of RA and gamma-HCD in a single patient is reviewed.
Adult↗