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D Haase

Publications and source records attributed to D Haase.

At least 55 records · Page 3Linked to original sources
PubMed1996

Induction of resistance in the human leukemia cell line HL60 towards hexadecylphosphocholine and other ether phospholipid analogues.

Hexadecylphosphocholine (HePC) is a new ether lipid analogue with remarkable antineoplastic activity in vitro and in vivo. As the precise molecular mechanism by which this substance and probably other ether lipids exert their biological effects is still not defined, we tried to approach this problem by generating a cell line resistant to the antiproliferative properties of HePC. This was successfully accomplished by slow adaptation over a period of 14 months, of the very sensitive human leukemia cell line HL60. HePC resistant HL60 cells (HL60R) tolerate 8- to 10-fold higher doses of HePC and are continuously cultured in medium containing 10 micrograms/ml of HePC. An immunophenotypic and karyotypic characterization of HL60 and HL60R cells showed only marginal differences between the two cell lines. Total phospholipids, total cholesterol, protein and vinyl ether lipid content were equal in both cells. A down-regulation of the ether lipid mass in HL60R of about 40% could reflect one mechanism of tolerance induction. Though HePC uptake in HL60R cells was significantly lower than in the parental line, steady state measurements of cellular HePC content revealed similar HePC content in the membranes at HePC concentrations that were cytotoxic for HL60 but did not affect HL60R. This observation indicates that uptake and cellular accumulation of HePC do not determine HePC resistance. The resistant HL60R cells also showed a considerable degree of cross-resistance to ether phospholipids ET-18-OCH3 and BM 41.440, suggesting a common mode of action for HePC and other ether lipid analogues.

Antigens, Surface↗
PubMed1995

Evidence for malignant transformation in acute myeloid leukemia at the level of early hematopoietic stem cells by cytogenetic analysis of CD34+ subpopulations.

Acute myeloid leukemia (AML) is a heterogenous disease according to morphology, immunophenotype, and genetics. The retained capacity of differentiation is the basis for the phenotypic classification of the bulk population of leukemic blasts and the identification of distinct subpopulations. Within the hierarchy of hematopoietic development and differentiation it is still unknown at which stage the malignant transformation occurs. It was our aim to analyze the potential involvement of cells with the immunophenotype of pluripotent stem cells in the leukemic process by the use of cytogenetic and cell sorting techniques. Cytogenetic analyses of bone marrow aspirates were performed in 13 patients with AML (11 de novo and 2 secondary) and showed karyotype abnormalities in 10 cases [2q+, +4, 6p, t(6:9), 7, +8 in 1 patient each and inv(16) in 4 patients each]. Aliquots of the samples were fractionated by fluorescence-activated cell sorting of CD34+ cells. Two subpopulations, CD34+/CD38- (early hematopoietic stem cells) and CD34+/CD38+ (more mature progenitor cells), were screened for karyotype aberations as a marker for leukemic cells. Clonal abnormalities and evaluable metaphases were found in 8 highly purified CD34+/CD38- populations and in 9 of the CD34+/CD38- specimens, respectively. In the majority of cases (CD34+/CD38-, 6 of 8 informative samples; CD34+/CD38+, 5 of 9 informative samples), the highly purified CD34+ specimens also contained cytogenetically normal cells. Secondary, progression-associated chromosomal changes (+8, 12) were identified in the CD34+/CD38- cells of 2 patients. We conclude that clonal karyotypic abnormalities are frequently found in the stem cell-like (CD34+/CD38-) and more mature (CD34+/CD38+) populations of patients with AML, irrespective of the phenotype of the bulk population of leukemic blasts and of the primary or secondary character of the leukemia. Our data suggest that, in AML, malignant transformation as well as disease progression may occur at the level of CD34+/CD38- cells with multilineage potential.

Acute Disease↗
PubMed1995

Cytogenetic findings in 179 patients with myelodysplastic syndromes.

Cytogenetic analyses were performed on 266 bone marrow and peripheral blood samples from 179 patients with myelodysplastic syndromes (MDS). According to the FAB classification, 42 patients presented with RA, 18 with RARS, 37 with RAEB, 22 with CMML, and 29 with RAEB-T. Nine patients showed a secondary MDS (S MDS). FAB classification was not available for 22 patients. Clonal karyotype anomalies were found in 92 patients (51.4%). Complex chromosome abnormalities occurred in 17 (18.5%) of them. An evolution of the karyotype was detected in 16 cases (17.4%). Cytogenetically independent cells or cell clones were found in eight patients. Nonclonal chromosome abnormalities were uncovered in 29 (16.2%) of the 179 MDS patients. Consecutive studies were performed in 48 patients and revealed a good correlation of initial karyotype and clinical course. The most frequent single anomalies were 5q- in 29 (31.5%), -7 in 22 (23.9%), trisomy 1q in 14 (15.2%), and +8 in 13 (14.1%) of 92 patients respectively. Our cytogenetic findings are presented in detail and discussed in relation to patients' age, morphological classification, clinical course, and prognostic impact. The contribution of cytogenetic findings to the delineation of multistep pathogenesis of MDS with special emphasis to karyotype instability is demonstrated.

Adult↗
PubMed1995

Management of pediatric acute hypoxemic respiratory insufficiency with bilevel positive pressure (BiPAP) nasal mask ventilation.

OBJECTIVES: To evaluate the efficacy and complications of noninvasive nasal mask bilevel continuous positive airway pressure ventilation in pediatric patients with hypoxemic respiratory insufficiency. DESIGN: Retrospective chart review. SETTING: Intensive care unit, university affiliated tertiary care children's hospital. PATIENTS AND METHODS: The study reviewed all patients admitted to the pediatric ICU with acute hypoxemic respiratory insufficiency who received bilevel noninvasive continuous nasal mask positive airway pressure delivered by a bilevel positive airway pressure system (BiPAP; Respironics Inc; Murrysville, Pa). RESULTS: Bilevel nasal mask positive pressure ventilation was utilized in 28 patients. Median patient age was 8 years (range, 4 to 204 months). The most common primary diagnosis was pneumonia. Nine patients demonstrated severe underlying neurologic disease or immunocompromise. Median duration of nasal mask ventilation was 72 h (range, 20 to 840 h). Clinical and laboratory variables immediately prior to bilevel nasal mask positive airway pressure and approximately 1 h after institution were evaluated. Respiratory rate decreased significantly with nasal mask ventilation (45 +/- 18 breaths per minute to 33 +/- 11, mean +/- SD, p < 0.001). Arterial blood gas PaO2 (71 +/- 13 mm Hg to 115 +/- 55), PaCO2, pulse oximetry saturation, and pH all improved significantly (p < 0.01). Using standard estimates for inspired oxygen, calculated alveolar-arterial gradients (271 +/- 157 to 117 +/- 65, p = 0.001), and PaO2/FIo2 ratios (141 +/- 54 to 280 +/- 146, p < 0.001), both improved significantly with nasal mask ventilation. Only 3 of 28 patients required intubation or reintubation. CONCLUSIONS: We conclude that noninvasive nasal positive pressure mask ventilation can be safely and effectively used in pediatric patients to improve oxygenation in mild to moderate hypoxemic respiratory insufficiency. It may be particularly useful in patients whose underlying condition warrants avoidance of intubation.

Acute Disease↗
PubMed1995

Trisomy 4 in 'stem cell-like' leukemic cells of a patient with AML.

CD34 positive progenitor cells were analyzed in the bone marrow aspirate from a patient with newly diagnosed AML FAB M4. The patient had trisomy 4 as sole cytogenetic abnormality and a dominant population of CD34 negative leukemic blasts. Karyotyping of the FACS isolated, minor subpopulation of CD34+/CD38-, 'stem cell'-like cells (incidence 0.29%) revealed trisomy 4 in 11/13 metaphases. No metaphases were obtained in the CD34 negative subpopulation. The experiments point to the existence of leukemic stem cells in the CD34+/CD38- compartment in AML patients with trisomy 4.

ADP-ribosyl Cyclase↗
PubMed1995

G-CSF in the long-term treatment of cyclic neutropenia and chronic idiopathic neutropenia in adult patients.

Eleven adult patients with chronic neutropenia have been treated with recombinant human granulocyte colony-stimulating factor (G-CSF). Seven patients had idiopathic sporadic neutropenia, 2 idiopathic congenital neutropenia and 2 cyclic neutropenia. Treatment was started with 3 micrograms/kg s.c. daily and was modified according to response. All patients had a rapid increase of neutrophils. The cycle length shortened from 21 to 14 days in patients with congenital cyclic neutropenia. Doses required for maintenance ranged from 0.1 to 8 micrograms/kg. One patient with idiopathic sporadic neutropenia recovered after 151 days with an absolute neutrophil count (ANC) of > 2000/microliters and had no need for further treatment. The overall efficacy of the treatment was good with abrogation of severe infections. Treatment has been continuously given to a maximum of 4.5 years. No loss of efficacy was observed during long-term treatment. There was no evidence for lineage drain or stem cell exhaustion with prolonged treatment. Cytogenetic analyses in seven of eleven patients did not reveal the development of abnormal cell-clones. G-CSF is safe and efficient in long-term treatment of adult patients with chronic neutropenias.

Adult↗
PubMed1994

[Complete remission in acute promyelocytic leukemia. The advantages of all-trans-retinoic acid compared to conventional chemotherapy].

In all of seven patients (six men, one woman; mean age 43 [24-55] years) with newly diagnosed acute promyelocytic leukaemia, treated between 1989 and 1993, complete remission was achieved. In three of these patients, treated between 1989 and 1991, remission was induced with conventional chemotherapy (cytarabine and anthracycline), after this in four patients with all-trans retinoic acid (tretinoin). The seventh patient who had a very rapid increase in leucocytes during tretinoin administration, was as a precaution also given conventional chemotherapy. All seven patients received consolidating chemotherapy with an intensive treatment cycle. Retrospective analysis indicated that induction with tretinoin had marked advantages: quicker regression of the clotting abnormalities (mean of 9 vs 25 days), shorter period of leukopenia (mean of 3.5 vs 30 days), shorter time until complete remission (mean of 38 vs 48 days). There were no specific side effects ascribable to tretinoin. Toxicity after chemotherapy corresponded to WHO grades 2-4. The results indicate that tretinoin markedly reduces the two main risks in the treatment of acute promyelocytic leukaemia: bleeding and infection.

Adult↗
PubMed1994

Semiautomated HLA-DQB1 typing by fluorescent dye photometry of amplified DNA on microtiter plates.

We report a simple semiautomated HLA class II typing method that suits the demands of a 24-hour-duty transplantation service for preorgan retrieval donor typing. The procedure consists of sequence-specific amplification of HLA alleles by the polymerase chain reaction (nested PCR-SSP) followed by fluorescent dye photometry of the resulting PCR products on microtiter plates. The entire typing procedure is semiautomated and completed in less than 90 minutes after DNA isolation. The test was evaluated for the definition of the specificities DQ1-DQ9 (generic HLA-DQB1 typing). Sensitivity and specificity as judged by DNA reference typing in a different laboratory was 99.5% (n = 202 alleles).

Alleles↗
PubMed1994

Comparison by extended ribotyping of Pseudomonas cepacia isolated from cystic fibrosis patients with acute and chronic infections.

Multiple isolates of Pseudomonas cepacia, from two cystic fibrosis (CF) patients who were chronically infected and two others who suffered acute fatal lung infections, were examined by multilocus enzyme electrophoresis and four-enzyme ribotyping. The strains isolated from the fatalities belonged to a clone, electropherotype 12 (ET12) that is endemic in the Ontario patients' province of origin. ET12 strains have also been isolated from outbreaks in CF patients in the United Kingdom, where they are considered to be strains of high virulence and transmissibility and epidemiologically related to Ontario strains. Four-enzyme ribotyping (EcoRI, Xho, PstI, and ClaI) established the close genetic relationship of the Ontario ET12 isolates and those from the United Kingdom, particularly an isolate from Manchester. In addition, four enzyme ribotypes of the sequential isolates taken during life and at autopsy of the ET12 clone were highly variable in comparison with the stability of the ribotypes of clone ET16 isolated sequentially from living chronic carriers. This extreme ribotype variability may be indicative of a highly virulent strain and poor prognosis. Isolates from our chronically infected CF patients belonged to a different clone, ET16, and it is also endemic in its region, 1000 miles east of ET12, in Nova Scotia. In both endemic circumstances, person-to-person transmission was easily demonstrated by four-enzyme ribotyping. The ET12 clone was found to be transmitted among summer campers and during a nosocomial outbreak, whereas an E16 strain was found to infect a sibling of a chronically infected patient; both infections were of the same ribotype.

Acute Disease↗
PubMed1993

Clinical aspects of acute myeloid leukemias of the FAB types M3 and M4Eo. The AML Cooperative Group.

Acute promyelocytic leukemia (AML FAB M3, APL) and acute myelomonocytic leukemia with abnormal eosinophils (AML M4Eo) are considered distinct entities with characteristic clinical, morphological, cytogenetic, and prognostic features. Promyelocytic leukemia is characterized by abnormal promyelocytes replacing normal hematopoiesis associated with a translocation between the long arms of chromosomes 15 and 17 t (15; 17), severe coagulopathy, and responsiveness to all-trans retinoic acid (tretinoin). Characteristic features of AML M4Eo are a myelomonocytic marrow infiltration, eosinophils with abnormal immature granules positive for chloroacetate esterase, an inversion or translocation of chromosome 16, and an increased risk of meningeal relapses. Prognosis of both types of AML has been reported to be better than prognosis of the other entities combined. Since most of the published data were collected from heterogeneous patient populations treated with various chemotherapeutic regimens, we have analyzed treatment outcome of AML M3 and M4Eo in the AMLCG-85 study for patients younger than 60 years. For the total population of 594 patients of this study, CR rate was 68.89%, early death rate 11.60%, and no or partial remission was achieved in 19.51% of the cases. Of 40 patients with AML M3 or M3 v complete remission was attained in 62.5%. Nine patients died within 42 days after the start of antileukemic therapy (22.5%). Of these nine, four died because of infection, five because of bleeding. Relapse-free survival rate was 59% after 3 years, significantly better than the respective curve of the other FAB types combined (35% after 3 years). In AML M4Eo, 91.7% of the 24 patients reached complete remission. The early death rate was 8.3%. No case of nonresponse was seen. Relapse-free survival rate was 49% after 3 years compared with 35% for the other types combined.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

Karyotype instability in myelodysplastic syndromes--a specific step in pathogenesis preceding clonal chromosome anomalies.

In a prospective study, 20 (11.6%) out of 172 patients with myelodysplastic syndromes (MDS) and two patients with aplastic anemia showed an increased spontaneous karyotype instability. No clonal chromosomal aberrations were detectable at the time of first examination. In three patients clonal anomalies developed during the course of the disease. In 17 out of 22 cases (77.2%) chromosomes 1, 5 or 7 were involved in nonclonal anomalies. The same chromosomes were frequently affected in patients with clonal abnormalities too. Our data suggest that spontaneous karyotype instability may be specific to a high proportion of cases with MDS and may constitute the source of clonal chromosome anomalies in these disorders.

Adult↗
PubMed1991

Partial trisomy 1q. A nonrandom primary chromosomal abnormality in myelodysplastic syndromes?

Cytogenetic and clinical data of 11 patients with de novo myelodysplastic syndromes and partial or total trisomy of the long arm of chromosome 1 are presented. In eight of these patients trisomy 1q was the sole karyotypic change and therefore can be classified as a primary chromosome anomaly. A remarkably young median age of 36.5 years was noticed in this patient group.

Adolescent↗
PubMed1990

Karyotype and in vitro-response to GM-CSF. Analysis of bone marrow cultures in leukemia, myelodysplasia and aplastic anemia.

The influence of GM-CSF on bone marrow cultures from 13 patients with aplastic anemia, MDS and acute leukemia was studied in a short-term suspension culture system. In each case combined cytogenetic and proliferation analyses were performed with respect to the question, whether chromosome aberrations play a role in the in vitro response to GM-CSF and in order to search for stimulating effects on malignant cells. The responsiveness was compared of aplastic and myelodysplastic cultures on the one hand and of leukemic cells on the other. Our results show that myelodysplastic and aplastic cells display a tendency for reduced susceptibility to GM-CSF as compared to healthy controls, while in leukemic bone marrow the response to the growth factor was significantly enhanced, indicating a leukemia-specific response pattern. In the majority of leukemias analyzed, the presence of cytogenetically abnormal cells in cultures with excessive response to GM-CSF can be taken as a proof for stimulation of malignant cells. The significance of these findings for pathogenesis and prognosis in aplastic anemia, myelodysplasia and leukemia is discussed.

Adolescent↗
PubMed1989

Investigations on the dose-dependent pharmacokinetics of adriamycin and its metabolites.

Four tumor patients with a normal liver function were each given twice 30 mg/m2 adriamycin (ADR) and then once 70 mg/m2 ADR in the form of 3-min intravenous bolus injections at three-week intervals. In addition to the first and third ADR administrations, the patients were each given p.o. 875 mg of antipyrine. During the six-week study period, the kinetics of antipyrine displayed a high degree of intra-individual constancy. Its CL varied between 75 and 119 percent intra-individually. The kinetic parameters of CL, AUC/dose, VDss, MRT and t1/2 gamma of ADR did not differ between dosages of 30 and 70 mg/m2. The ADR-dose-standardized AUC10-40 min of adriamycinol (ADR-OH), its concentration time product at the times of its highest concentration in plasma, did not display any dependence upon the ADR dose. The AUCADR-OH/dose quotient, however, was found to be significantly higher (p less than 0.05) at 70 mg/m2 than at 30 mg/m2. The MTR and the t1/2z of ADR-OH showed a trend towards prolongation at 70 mg/m2. The ADR-dose-standardized AUC of the aglycones showed no dependence upon the ADR dose while the ADR-dose-standardized AUC10-40 min of the aglycones was significantly lower at a high ADR dose (p less than 0.05) than at a small ADR dose. The results suggest that in the ADR dose range studied the ADR pharmacokinetics is dose-independent and linear, and the rate at which ADR-OH, its main metabolite is formed, is also dose-independent. In contrast, the elimination of ADR-OH seems to be capacity-limited.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

Are health care workers at risk for infection during an outbreak of nosocomial Legionnaires' disease?

We studied data from 500 health care workers to answer the question: Are health care workers at risk for infection during an outbreak of nosocomial Legionnaires' disease? These workers were employed at a hospital where eight cases of nosocomial Legionella pneumophila serogroup 1 pneumonia occurred over a 4-week period. The source was potable water. Acute-phase blood samples were collected on the day the water supply was decontaminated, convalescent samples were collected 4 to 6 weeks later from 373 subjects, and a single serum sample was obtained from an additional 127 subjects. Antibody titers to L. pneumophila were determined by an indirect immunofluorescent antibody (IFA) technique and by a microagglutination assay with the epidemic strain as the test antigen. Subjects who had an IFA titer of greater than or equal to 1:256 were retested with an anti-human IgM conjugate. None of the 373 health care workers had a fourfold rise in antibody titer. The geometric mean antibody titer of 73.8 for the 500 health care workers was significantly higher than that of 68.1 for 976 blood donors (p less than 0.01). Only 2.4% had recent infection as evidenced by a microagglutination test, despite the fact that 84% were susceptible. We conclude that in the setting of a short-term outbreak of Legionnaires' disease caused by contaminated potable water the risk of infection among health care workers is low: 2.4% or less.

Adult↗