摘要:

AbstractPeripheral blood lymphocytes from 16 aplastic anemia patients were studied for in vitro biosynthesis of immunoglobulins (Ig), proliferative responses, and cell markers before and after antithymocyte globulin (ATG) treatment in an attempt to identify immune functions that would be useful in predicting responses to ATG therapy. Six of the 16 aplastic anemia patients were complete responders to ATG therapy, two were partial responders, and eight failed to respond to ATG therapy. The proportion of E+, CD4, CD8, and surface Ig‐positive cells did not correlate with in vitro lymphocyte functions nor clinical responses before or after ATG therapy. Lymphocyte proliferative responses to phytohemagglutinin, tetanus toxoid, alloantigens, or pokeweed mitogen were generally present before and after ATG therapy. When pokeweed mitogen, herpes simplex type I virus, and tetanus toxoid were used as probes to elicit in vitro Ig production using a hemolytic plaque assay, some patients had 1) B cells that failed to produce Ig, 2) T cells that failed to provide helper activity, and 3) T cells that exhibited excessive suppressor activity in the various antibody production systems. These measures of immune function, however, did not correlate with clinical responses to ATG therap

ISSN:0361-8609    

DOI:10.1002/ajh.2830260102

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1987

数据来源: WILEY

摘要:

AbstractMembrane transport—sodium (Na+) influx and calcium (Ca2+) uptake—was examined in human mature red cells treated with phospholipase A2(PLase A2) from snake venom. PLase A2‐induced conversion of phosphatidyl choline (PC) to lysophosphatidyl choline (L‐PC) was associated with a marked increase in Na+influx and Ca2+uptake. After L‐PC was removed from the cell membrane of the PLase A2‐treated red cells in the presence of albumin, an additional increase in Ca2+transport was observed. These results indicate that membrane lipid abnormalities, such as increased L‐PC and/or a loss of total lipids, appear to induce increased membr

ISSN:0361-8609    

DOI:10.1002/ajh.2830260103

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1987

数据来源: WILEY

摘要:

AbstractThe rate of influx of22Na+into human erythrocytes (RBC) varies greatly depending upon the donor. A high rate of influx may be related to a congenital predisposition to essential hypertension. In Northern Europeans, we find a threefold difference in the rate of22Na+influx between those with the least (LP) and most highly permeable (HP) RBC (fromtwofold) in RBC22Na+influx rate. We find that the loop diuretics furosemide and bumetanide decrease by about 50% the influx of22Na+into HP RBC, but have a lesser influence on LP RBC. Impermeant polyanions such as citrate and pyrophosphate also specifically diminish22Na+influx into HP, but not LP, RBC. Therefore, the exaggerated22Na+influx into HP RBC probably occurs through a discrete pathway (perhaps via “Na/K/Cl cotransport”), which appears to be almost absent in LP RBC. The differences between HP and LP RBC most likely do not involve polymorphisms of RBC anion transport per se. The rate of RBC anion (35SO42–) transport is the same in HP and LP RBC and is equally inhibited by furosemide and (to a lesser extent) bumetanide. Furthermore, the potent inhibitor of RBC anion transport, DIDS (diisothiocyanostilbene disulfonate) does not affect RBC Na+permeability in either group. Nonetheless, the preferential reduction of Na+permeation of HP RBC by loop diuretics may be of help in experimentally distinguishing HP from LP phenotypes. This information may be crucial in unraveling the structural basis of intrinsic differences in cell membrane Na+permeability and their possible relationship to essential hyperte

ISSN:0361-8609    

DOI:10.1002/ajh.2830260104

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1987

数据来源: WILEY

摘要:

AbstractThe oxidized form of glutathione transport was studied in human erythrocytes in pyrimidine 5′‐nucleotidase (P5N) deficiency, a disorder in which the amounts of CTP and UTP in the erythrocytes are elevated. The inhibition of ATP‐requiring oxidized glutathione (GSSG) transport by CTP and UTP is believed to play a role in elevating the levels of the reduced form of glutathione (GSH) in the erythrocytes of patients with P5N deficiency. The current investigation was undertaken to determine if GSSG transport actually decreases in the erythrocytes of such patients. Erythrocytes from a 17‐year‐old patient and a 13‐year‐old patient with P5N deficiency hemolytic anemia and from ten normal subjects were used as materials for the experiment. Erythrocytes, which had been previously incubated with [3H]glycine, were incubated at 37°C, and the rate of [3H]GSSG transported by the cells was estimated. The velocity of GSSG transport out of the erythrocytes was quite low in the patients, 3.17–3.65 nmol GSSG/ml erythrocytes/hr at 37°C in one case, and 3.30 nmol GSSG/ml erythrocytes/hr in the other case, vs that in the normal controls (6.00 ± 0.80 nmol GSSG/ml erythrocytes/hr; mean ± SD). The activity of γ‐glutamylcysteine synthetase and glutathione synthetase did not decrease in the patients. Decreased transport activity of GSSG in addition to a normal synthesis rate for GSH may explain the increased concentration of erythrocyte

ISSN:0361-8609    

DOI:10.1002/ajh.2830260105

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1987

数据来源: WILEY

摘要:

AbstractA common acute lymphoblastic leukemia (ALL) cell line, designated LC4‐1, was established from peripheral blood mononuclear cells of a patient with acute non‐T‐cell ALL. LC4‐1 cells were characteristically positive for Ia, B4, and common ALL antigens (CALLA), but negative for B2, Tac, T3, T4, T8, T11, and M1 antigens and E‐rosette formation. Approximately 30% of LC4‐1 cells expressed detectable amounts of B1 antigens. LC4‐1 cells expressed neither Epstein‐Barr‐virus–associated nuclear antigen (EBNA), cytoplasmic immunoglobulins (cIg) nor surface immunoglobulins (sIg). Gene rearrangements had already occurred in LC4‐1 in the D‐J region of immunoglobulin heavy chain genes, but not in T‐cell receptor (β‐chain) genes, suggesting that LC4‐1 is a progenitor cell line of B‐cell lineage earlier than pre‐B‐cells.The expression of cell surface antigens of LC4‐1 was changed by treatment with 4‐phorbol 12‐myristate 13‐acetate (PMA) (0.1 ng/ml) for 2 days. Before treatment with PMA, about 98% of LC4‐1 cells were positive for B4, CALLA, and Ia. However, following treatment they lost CALLA expression without any change in expression of Ia and B4. There was no change in B1‐positive population. The change in surface antigens on LC4‐1 cells seems to be due to differentiation induced in the cells by PMA. These results support the hypothesis that CALLA is a differentiation antigen and suggest on

ISSN:0361-8609    

DOI:10.1002/ajh.2830260106

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1987

数据来源: WILEY

摘要:

AbstractPeripheral blood lymphocytes from two Chediak‐Higashi syndrome (CHS) patients were examined for their 1) natural killer (NK) cell functions 2) concanavalin A (Con A)‐inducible suppressor cell activity, 3) soluble suppressor factor production, and 4) responsiveness to interferon alpha and interleukin‐2 in comparison with age‐matched normal controls. Peripheral blood lymphocytes or NK‐enriched large granular lymphocytes from Chediak‐Higashi syndrome patients showed negligible cytotoxic activity against several target cells. Although the NK activity of Chediak‐Higashi syndrome lymphocytes could not be restored to normal levels by treatment with either interferon or interleukin‐2, the percent enhancement of NK activity was higher for the patients than the controls. Soluble suppressor factor activity of culture supernates from the lymphocytes of Chediak‐Higashi syndrome patients significantly inhibited the NK activity of allogeneic, normal peripheral blood lymphocytes, whereas lymphocytes from Chediak‐Higashi syndrome patients precultured with Con A failed to suppress the cytotoxic activity of normal lymphocytes. These results demonstrate a previously unrecognized suppressor cell dysfunct

ISSN:0361-8609    

DOI:10.1002/ajh.2830260107

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1987

数据来源: WILEY

摘要:

Abstractγ‐Glutamyltranspeptidase (GGT) acitivity (per mg protein) in blood lymphoid cells of 27 children with acute lymphoblastic leukemia (ALL) (1.05 ± 0.15) was significantly below that of controls (2.25 ± 0.30), became normalized during chemotherapy‐induced remission (2.47 ± 0.26), and was low again (1.59 ± 0.62) in relapsed subjects. Individual variations in the GGT activity of the blood lymphoid cell fraction (per mg protein) bore a significant inverse correlation to the number of white blood cells (WBC) as well as of blasts per ml blood. Blasts had minimal GGT activity; however, partial GGT deficiency was also exhibited by the microscopically normal circulatory lymphocytes of several patients prior to treatment and in relapsed subjects whose blood was still devoid of blasts.Significantly diminished GGT activity (per mg protein) was found in the blood granulocytes of ALL subjects. This deficit, restored during remission and present again at relapse, varied in magnitude but showed no statistically significant correlation to the different patients' degree of neutropenia. In about one‐third of the newly diagnosed or relapsed pre‐B ALL children, the circulatory granulocytes' GGT activity was only 10–20% of normal. The results suggest that 1) the presence or absence of this sign of functional maldifferentiation in granulocytes is a factor in the heterogeneity of disease manifestation among subjects with apparently the same type of ALL and that 2) measurement of GGT in the circulatory granulocytes, as well lymphocytes, may be useful for monitoring the efficacy o

ISSN:0361-8609    

DOI:10.1002/ajh.2830260108

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1987

数据来源: WILEY

摘要:

AbstractTwo patients with acute myelomonocytic leukemia (AML‐M4) and a specific chromosomal translocation t(6;9)(p23;q34) are reported and compared to 21 AML patients with the same translocation collected from the literature. Our observations suggest that AML with t(6;9)(p23;q34) is characterized by myelodysplasia, basophilia, and a variety of blast cell morphologies (M1, M2, M4) with a greater proportion of the cases than previously appreciated being examples of acute myelomonocytic leukemia (AML‐M4). The consistent association of myelodysplasia provokes the proposal that this subtype of de novo AML is a result of an acute stem cell disorder. The poor outcome with standard AML chemotherapy experienced in this group of relatively young patients necessitates consideration of alternative therapeutic strategies such as early bone marrow transplantat

ISSN:0361-8609    

DOI:10.1002/ajh.2830260109

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1987

数据来源: WILEY

摘要:

AbstractAntithymocyte globulin (ATG) is an established form of therapy for severe aplastic anemia (SAA). However, in patients who do not respond to this treatment and who are not candidates for bone marrow transplantation few successful therapeutic alternatives exist. We report two such patients who have shown a therapeutic response to Cyclosporin A (CSA) (Sandimmune, Sandoz). Case 1, a 15 year old male, and Case 2, a 34 year old female, were diagnosed as having SAA in September 1984 and May 1984 respectively. Treatment with high dose Methylprednisolone (MPN) and ATG in Case 1 and MPN, ATG and Oxymetholone in Case 2 for ten days was ineffective in both cases. Case 1 developed anaphylaxis with both repeat ATG and ALG (antilymphoblast globulin), and Case 2 failed to respond to repeat ATG. Both required frequent packed cells and platelet transfusions.At five and six months respectively following completion of ATG therapy, CSA was started at 10 mg/kg/day in divided doses orally. Renal and liver functions and CSA blood levels were followed. Within six weeks both patients exhibited a hematologic response and were no longer transfusion dependent. On maintenance therapy of 4 mg/kg/day (Case 1) and four months after discontinuing CSA (Case 2) the hematologic values are as follows: hemoglobin 160 and 130 g/L, absolute granulocyte count 3100 and 1640 × 109/L, and platelets 132 and 84 × 109/L respectively. Side effects included hypertrichosis, gingival hyperplasia and mild reversible nephrotoxicity. CSA appears to represent an effective form of therapy for patients with SAA refractory to AT

ISSN:0361-8609    

DOI:10.1002/ajh.2830260110

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1987

数据来源: WILEY

摘要:

AbstractThe high specifity of the “pink test” for the detection of hereditary spherocytosis has been confirmed. A modification of the test is proposed that requires only 10 μl of blood taken without anticoagulant (a “direct pink test”), thus eliminating the necessity of venipuncture, especially cumbersome in newborns and

ISSN:0361-8609    

DOI:10.1002/ajh.2830260111

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1987

数据来源: WILEY