摘要:

Abstract:The traditional classification of neutrophil granules as peroxidase‐positive (azurophil, or primary) and peroxidase‐negative (specific or secondary) has proven to be too simple to explain the differential exocytosis of granule proteins and incorporation of granule membrane into the plasma membrane which is an important aspect of neutrophil activation. Combined subcellular fractionation and immunoelectron microscopy has revealed heterogeneity among both peroxidase‐positive and peroxidase‐negative granules with regard to their content, mobilization and time of formation. Peroxidase‐negative granules may be classified according to their content of lactoferrin and gelatinase: 15% of peroxidase‐negative granules contain lactoferrin, but no gelatinase. 60% contain both lactoferrin and gelatinase. The term specific or secondary granule should be reserved for these two subsets. In addition, 25% of peroxidase‐negative granules contain gelatinase but no lactoferrin. These should be termed gelatinase granules or tertiary granules. Gelatinase granules are formed later than specific granules and mobilized more readily. In addition, a distinct, highly mobilizable intracellular compartment, the secretory vesicle, has now been recognized as an important store of surface membrane‐bound receptors. This compartment is formed in band cells and segmented cells by endocytosis. This heterogeneity among the neutrophil granules is of functional significance, and may also be reflected in the dysmaturation which is an important feature of myeloproliferative and myelodyspl

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1993.tb00629.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Abstract:Cardiac involvement in hereditary haemochromatosis (HH) is a poor prognostic sign and is the main cause of death in the juvenile form. The treatment of choice is iron removal therapy by phlebotomy, but treatment by iron chelation (desferrioxamine) has been recommended in cases with severe cardiac symptoms. We describe here the first case of juvenile HH undergoing heart transplantation, which became necessary despite intensive iron removal therapy by phlebotomy and treatment by desferrioxamine. Throughout the course the myocardial iron content was monitored by endomyocardial biopsies and by magnetic resonance imaging (MRI). At the last follow‐up, 18 months after transplantation, the myocardial iron content in the transplanted heart was still within reference ranges by biochemical determination and MRI and the patient's condition was completely satisfactory. In conclusion, heart transplantation should be considered in cases of severe juvenile HH. In the follow‐up of these patients MRI may be a useful supplem

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1993.tb00630.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Abstract:67‐gallium accumulates rather selectively in malignant lymphoid tissue. The isotope has a substantial cytotoxic effect in human‐derived cell‐lines. 67‐gallium was given intravenously to 3 patients with end‐stage, resistant large‐cell lymphoma. Evaluation of tumour response was done by physical measurements, and CT‐scanning together with gallium scintigraphy. Three weekly doses of 20, 40 and 60 mCi respectively caused persistent pancytopenia in 1 patient. Panycytopenia was not observed in 2 other patients given two 40 mCi doses 4 weeks apart. In all 3 patients, some response was noted, be it shortlived and different from site to site. 67‐gallium has some cytostatic effect in large cell lymphoma. It seems feasible to start a phase I study to find a tolerable dose to be give

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1993.tb00631.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Abstract:We have previously reported that the antineoplastic activity of 3′ ‐azido 3′ deoxythymidine (AZT) can be increased by drugs that inhibit “de novo” thymidylate synthesis, such as 5‐fluorouracil, methotrexate and hydroxyurea. In the present study we tested the combinations AZT + alpha interferon (IFN) and AZT + gamma IFN onin vitrogrowth of the human acute‐phase chronic myeloid leukemia (CML) cell line K562. After 72 hours incubation, not only AZT + α‐IFN but also AZT + γ‐IFN were synergistic in inhibiting K562 growth, as demonstrated by isobologram analysis of the data. This enhanced cytotoxicity was confirmed by the evaluation of [3H]AZT incorporation into cellular DNA, that was increased by 50% and 222% in the presence of α‐ and γ‐IFN, respectively. The addition of 50 μmol/l thymidine to the culture medium was able to reduce the cytotoxicity of the drug combinations to the degree observed with each compound alone; furthermore, the increased incorporation of AZT into DNA was completely reversed. These data indicate the existence of a biochemical interaction between AZT and IFNs that results in an increased cytotoxic effect. While the combination AZT + α‐IFN is currently being tested in HIV‐related malignancies, AZT + γ‐IFN is new and deserves further study in human CML acute and chronic phase models, in view

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1993.tb00632.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Abstract:As in western Europe and the USA, chronic lymphocytic leukaemia (CLL) in Latvia is the most prevalent type of leukaemia. A total of 1509 newly diagnosed cases of B‐cell chronic lymphocytic leukaemia entered the study, 440 of whom were followed up at the Latvian Haematology Centre. The main peculiarities of the study were: 1) the higher incidence of the disease in Latvia as compared with other regions of the former USSR and with western countries, 2) a lower male‐to‐female ratio than in most other countries and 3) a higher morbidity among the Latvian population in comparison with the Russian. A positive correlation between the disease stage and survival was confirmed, but no precise individual prognosis in an early stage of the disease was pos

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1993.tb00633.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Abstract:Chronic granulomatous disease (CGD) is characterized by the inability of the patients' phagocytic leukocytes to generate superoxide. Therefore, these cells fail to kill certain bacteria and fungi. As a result, patients with CGD suffer from recurrent, life‐threatening infections with these micro‐organisms. Superoxide is produced by NADPH oxidase, a multicomponent enzyme exclusively present in phagocytic leukocytes. The most common form of CGD is X‐linked, originating from a deficiency of the high‐molecular‐weight subunit of cytochromeb558(gp91‐phox). Here we describe a patient suffering from X‐linked CGD due to a 40‐base‐pair duplication in exon 7 of the CYBB gene coding for gp91‐phox, predicting a frameshift, substitution of 22 amino acids and a premature stop codon at amino‐acid position 253. The mother as well as the grandmother of this patient were proven to be heterozygous for this mutation; the father and sister were normal. However, the great‐grandmother proved to have normal oxidative functions, suggesting that the mutation occurred three generations ago. This is the first description of a nucleotide dup

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1993.tb00634.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Abstract:Recently, a superoxide‐generating NADPH‐oxidase system in human fibroblasts has been described. Therefore, we reassessed the possible use of this cell type for prenatal diagnosis of CGD patients comparing normal and CGD peripheral blood neutrophils (PMN) and skin fibroblasts in their reactive oxygen intermediate (ROI)‐producing capacity. While PMN of the CGD patient showed a clearly reduced respiratory burst activity, which correlated well with the measured content of cytochrome b558, fibroblasts of the same individual showed no impaired production of superoxide anion or H2O2upon stimulation by cytokines (TNF and IL‐1) or other agents (Ca2+ionophores and PAF, unpublished results). Furthermore, fibroblasts of the CGD patient or of normal donors could be inhibited in ROI production by diphenylene iodonium (DPI) and 2‐iodobiphenyl. In contrast to PMN, no inhibition of the fibroblast NADPH‐oxidase system was observed using staurosporin, an inhibitor of proteinkinase C. These data demonstrate, in contrast to previous studies, that fibroblasts are able to produce ROI. Nevertheless, since fibroblasts obtained from a CGD patient exhibited no difference in ROI production compared with fibroblasts obtained from healthy donors, they are not suitable for prenatal diagn

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1993.tb00635.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Abstract:Patients with polycythaemia and normal controls have been studied to establish and subsequently test non‐conventional criteria for the diagnosis of primary polycythaemia (primary proliferative polycythaemia, polycythaemia vera) as compared with conventional Polycythaemia Vera Study Group (PVSG) assessment. One criterion was erythroid colony formation from peripheral blood in a serum‐free system, assayed alone and with the addition of recombinant human erythropoietin (Epo), interleukin 3 (IL3), or α interferon (α‐IFN) (Dudley et al. 1990). The remaining criteria were non‐culture associated and comprised platelet distribution width (PDW), platelet nucleotide ratio (ATP:ADP), serum erythropoietin and clinical evidence of ischaemic vascular disease. The combination of culture associated and non‐culture associated variables, by use of a simple additive scoring system, gave no false positive and only 6% false negative results in distinguishing primary polycythaemia from other polycythaemias and normal controls in those (34 patients Group A) used in its derivation. Testing the scoring system in a newly presenting group (25 patients Group B) was highly satisfactory with no false positives and only a few false negative results (14%). Use of these non‐conventional criteria should allow more confident diagnosis of primary polycythaemia, where conventional clinical and laboratory assessment is

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1993.tb00636.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Abstract:To determine the locus of platelet production, we sought to determine if sufficient megakaryocytes reach the lungs in a state that could produce platelets. Elutriation was used to isolate megakaryocytes from blood reaching and leaving the lungs of 20 patients undergoing routine cardiac catheterizations. A mean of 5.0 intact megakaryocytes/ml were found in pulmonary artery blood, compared to only 0.5 megakaryocytes/ml, with partial cytoplasmic content, in aortic samples. The megakaryocytes in central venous and aortic samples were all mature. The identity of these cells as megakaryocytes, their maturity and normal morphology were confirmed by standard and immunoelectron microscopy. Cardiac outputs were obtained for each patient at the time of blood sampling, allowing an extrapolation that 40 × 106intact, mature megakaryocytes were being delivered to the lungs every day in the average patient, compared to only 4.0 × 106partially spent megakaryocytes exiting the lungs daily. About 98% of megakaryocyte cytoplasm reaching the lungs did not exit as recognizable megakaryocytes or fragments. The number and state of the megakaryocytes apparently filtered in the lungs is consistent with the hypothesis that megakaryocytes may shed platelets within the pulmonary microvasculature, which may be the primary site of platelet productio

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1993.tb00637.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Abstract:The aim of this study was to investigate individual pharmacokinetics as a tool for dosing of factor VIII (FVIII) in severe hemophilia A. It is assumed that effective prophylaxis against bleedings is maintained if the plasma FVIII:C activity is kept above 1 U/dl, and the present study is based on this assumption. A current standard dosage regimen for FVIII is 25–40 U/kg up to three times weekly. However, there is considerable individual variation in the pharmacokinetics of FVIII:C. Individual pharmacokinetic data were used to computer‐simulate plasma activity curves after repeated doses in 8 patients. Going from prophylaxis regimens of normally 2–3 infusions per week to dosing every 2 days would theoretically reduce their average FVIII consumption by 43% with maintained or increased trough levels of FVIII:C. Daily dosing would reduce their mean FVIII usage by 82%. Modified dosage regimens, infusions every 2 days, were implemented in the patients, and plasma samples were drawn to verify the pharmacokinetic models. The feasibility of the method to generally raise trough levels with a decreased consumption of FVIII was confirmed. Dosing of coagulation factors according to kinetic principles can result in more cost‐effective utilization of these very expensive prepa

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1993.tb00638.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY