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Biomedical subjects

D Lutz

Publications and source records attributed to D Lutz.

At least 91 records · Page 5Linked to original sources
PubMed1985

[Prognostic factors in myelodysplastic syndromes: analysis of 72 cases].

72 patients were diagnosed as suffering from myelodysplastic syndromes (MDS) according to the FAB classification: 16 patients with refractory anaemia (RA), 11 patients with acquired idiopathic sideroblastic anaemia (AISA), 14 patients with refractory anaemia with an excess of blast cells (RAEB), 7 patients with RAEB in transformation (RAEB/t) and 24 patients with chronic myelomonocytic leukaemia (CMML). The duration of the preleukaemic phase was between 2 and 189 months (median: 15 months); RAEB in transformation and CMML showed a median phase of less than 12 months. Transformation into acute leukaemia (AL) occurred in 46 patients (64%). Of the clinical signs only thrombocytopenia was a significant poor prognostic factor (p less than 0.01). Cytogenetic studies were made in 31 patients. 14 had clonal aneuploidy: these patients had a higher risk of AL, but not a significantly shorter preleukaemic phase (p greater than 0.1). Stem cell cultures (CFUc) were carried out in 31 patients. Patients without colony growth or only cluster growth showed a high incidence (10/11 and 8/8) of transformation into AL; preleukaemic phases were significantly shorter than in patients with normal colony growth or cluster + colony growth in all FAB subgroups (p less than 0.001). The bone marrow blast cell count was indirectly proportional to the duration of the preleukaemic phase: thrombocytopenia, cytogenic aberrations and failure of in vitro colony growth are additional poor prognostic factors in MDS.

Adult↗
PubMed1985

Surface glycoproteins (S-GP) on normal and malignant human leukocytes.

This study aimed to investigate high molecular weight surface glycoprotein (S-GP) patterns on various types of human leukocytes. S-GP were externally labelled by the Galactose-oxidase-NaB3H4 technique. Results based on the analysis of 120 samples derived from different types of normal and malignant leukocytes indicate that the relative expression of high molecular weight S-GPs changes during haemopoietic cell differentiation and to some extent these changes enable the classification of human leukocytes.

Antigens, Surface↗
PubMed1985

Cell lineage heterogeneity in blast crisis of chronic myeloid leukaemia.

Blast cells from 45 patients with chronic myeloid leukaemia in blast crisis (CML-BC) were immunologically phenotyped with a panel of 26 monoclonal antibodies and studied for terminal deoxynucleotidyl transferase (TdT) content. Out of 45 blast-populations, 28 showed a myeloid, 14 a lymphoid, two a mixed and one an unclassifiable marker profile. In contrast to acute myeloid leukaemia (AML), we found frequent involvement of the thrombopoietic and erythropoietic systems in myeloid CML-BC. Furthermore, the marker profile on blast cells in myeloid CML-BC was different from that seen in AML. The blast cells in lymphoid blast crises of CML displayed the same lymphoid marker profile as those in acute lymphoblastic leukaemia. In three of 16 patients who were serially tested, we observed phenotypic changes in the blast cell populations. In one patient the blasts changed from lymphoid to myeloid type while remaining TdT-positive; in another case the blasts switched from granulomonocytic TdT-negative to granulomonocytic TdT-positive. In the third patient erythroid precursor cells appeared as the disease progressed. The results indicate the capacity of blast populations in CML-patients during blast crisis to differentiate along several pathways.

Adolescent↗
PubMed1985

[The bioavailability and pharmacokinetics of two carbocysteine preparations after single and multiple dosing].

The relative bioavailabilities and pharmacokinetic profiles of 2 carbocisteine preparations (capsules, granulate) were evaluated in a single dose and a steady state study. 10 healthy volunteers took in a randomized, 2fold cross over design 750 mg 3-(carboxymethylthio)alanine (carbocisteine, Transbronchin) (1 portion of the granulate or 2 capsules) as a single dose or for 4 days 3 times a day (every 8 h) 1 portion of the granulate or 2 capsules, respectively. During the saturation phase the pre-dose serum levels in the morning were determined and on day 5 - after a last dosing the elimination kinetics were evaluated. The same time frame of blood withdrawals was used for the evaluation of serum kinetics after single dosing. The new developed gaschromatographic method for the rapid, sensitive and reliable quantitative determination of carbocisteine in serum saves not only a lot of time but also improves the detection limit and selectivity by a factor of approx. 10. The studies revealed bioequivalency of the carbocisteine granulate and capsule preparations. After multiple dosing, no cumulation of the carbocisteine serum levels occurred. A comparison of the AUCo-infinity and AUC tau (single/multiple dosing, respectively) showed linear pharmacokinetics without enzyme induction or saturation phenomena in man.

Adult↗
PubMed1985

[Bioavailability of new nifedipine preparations in man. 1. Pharmacokinetics of nifedipine in the form of sustained-release tablets].

Following a single dose of a 20 mg nifedipine retard-tablet (Pidilat retard or a marketed formulation) to 12 healthy volunteers in a randomized, two-fold cross-over trial the nifedipine plasma levels were quantitatively determined by gas chromatography up to 24 h p.a. The relative bioavailabilities and important pharmacokinetic parameters were calculated and then statistically evaluated for significant differences between the preparations. Approx. 2 h after dosing, peak concentrations of 13 to 74 ng/ml were reached, the minimal therapeutic plasma level of 10-15 ng/ml was - in general - upheld for 10 respectively 8 h. Terminal elimination half-lives were calculated to be 5 and 8 h, respectively. An extrapolation with the obtained data for the expected steady state plasma levels after a twice-a-day dosing showed that the above mentioned therapeutically relevant plasma levels of the unchanged drug are in general achieved for most of the dosage interval. The strong inter- and intraindividual variations of blood levels after nifedipine application, which have already been described by numerous other authors, could also be observed in this study.

Adolescent↗
PubMed1985

[Bioavailability of new nifedipine preparations in man. 2. Bioequivalence of nifedipine in the form of soft gelatin capsules].

In a randomized, two-fold cross-over design 12 healthy volunteers received a normal-release 10 mg nifedipine soft gelatine capsule (Pidilat or a marketed product, respectively). The quantitative determination of the drug in plasma was achieved by gas chromatography up to 24 h p.a. Some important pharmacokinetic parameters and the relative bioavailabilities of the preparations were calculated and subsequently compared statistically: statistically significant differences between the preparations could not be found. Mean peak plasma concentrations of 121.2 +/- 47.3 and 104.5 +/- 32.9 ng/ml were reached approximately 0.5 h p.a. Both plasma level curves were practically identical, with the exception of the obtained absolute peak plasma concentrations. The known strong inter- and intraindividual variations of the plasma levels were found to be less pronounced in this study.

Adolescent↗
PubMed1984

M2, a novel myelomonocytic cell surface antigen and its distribution on leukemic cells.

The selectivity of a novel myelomonocytic cell surface antigen, designated M2, has been assessed in a series of 208 leukemias. The M2 antigen is defined by a monoclonal antibody (VIM-2) of the IgM class. Its expression within the normal hemopoietic system is restricted to myelomonocytic cells. Lymphocytes, erythrocytes, thrombocytes and their morphologically recognizable precursors are negative. Sixty of the 66 acute myeloblastic leukemias (= 91%) and 28 of the 30 myeloid blast crises of CML patients (= 93%) were M2-positive. As expected from our findings with normal myeloid cells, the myeloid cells found in stable phase of CML were also in all instances, M2-positive. Quite in contrast, lymphoid cells from patients with B-CLL, T-CLL, prolymphocytic leukemia, hairy-cell leukemia, lymphoblastic lymphoma, Sézary syndrome, from CML patients in lymphoid blast crisis and from the majority of patients with ALL, were completely M2-negative. Also negative were the blast cells of patients with acute megakaryoblastic leukemia and acute erythroleukemia. A direct comparison of M2 expression with the display of the 3-fucosyl-N-acetyllactosamine determinant, the structure recognized by most of the anti-myeloid monoclonal antibodies reported so far, shows that more AMLs are M2-positive and the proportion of M2-positive blast cells in individual AML samples is higher.

Antibodies, Monoclonal↗
PubMed1984

Diagnostic specificity of the monoclonal anti-CALLA antibody VIL-A1 in leukemia and malignant lymphoma.

VIL-A1 is an anti-CALLA antibody which binds efficiently and exclusively to CALLA positive cells. When the cell type specificity of VIL-A1 is studied in acute leukemias and lymphomas, results show that in those leukemias which could be characterized by cytochemical and morphological methods, VIL-A1 reactivity was specific for cells of lymphoid origin. It can therefore be assumed that VIL-A1 positive AUL cells (in this case 4 out of 9 patients) are also lymphoid in origin. In no case were AML blasts found to be positive with this antibody. Seventy-four per cent of the 88 ALL patients were positive (L1 + L2) whereas none in the L3 subgroup were positive, and 48% of CML patients in blastic crisis were positive. Of the low grade non-Hodgkin malignancies, only CB/CC was positive, distinguishing it from the CC type which was negative. Of the high grade lymphomas IB was found to be negative, while the others showed a heterogeneous picture which was not related to other immunological parameters.

Acute Disease↗
PubMed1984

Exposure by desialylation of myeloid antigens on acute lymphoblastic leukemia cells.

The 3-fucosyl-N-acetyllactosamine structure, a sugar sequence contained in the human milk oligosaccharide lacto-N-fucopentaose III, is recognized by most of the granulocyte-specific monoclonal antibodies (MoAb) reported in the literature, including the six MoAb from our laboratory. Blast cells from patients with acute myeloblastic leukemia (AML) displayed a heterogeneous reaction pattern when they were exposed to MoAb against this moiety, and the proportion of reactive cells in individual cell samples was highly variable. The intensity of the reaction was strongly enhanced by neuraminidase treatment of AML blasts, and reactive structures were exposed on previously negative AML blast cells. Surprisingly, this granulocyte-associated antigen was exposed by desialylation not only on malignant myeloid precursor cells but also on common acute lymphoblastic leukemia cells. No such effect was seen when normal peripheral blood lymphocytes, lymphocytes from patients with chronic lymphatic leukemia, or blast cells from patients with B-cell acute lymphoblastic leukemia, acute erythroid leukemia, and acute megakaryoblastic leukemia were treated with neuraminidase.

Animals↗
PubMed1984

Cellular discriminants for a biological classification of human colon carcinoma.

We categorized established human colon carcinoma cell lines into three biological groups. Our studies were performed on six colorectal cancer lines representing the proposed three groups. Group I consisted of two lines designated LoVo and SW 48; Group II comprised two lines called SW 480 and SW 620; and Group III was represented by lines SW 403 and SW 1116. Group I consisted of the most differentiated cells. This differentiation encompassed morphological markers, gland and signet ring formation, and ciliary development. The outstanding morphological characteristic of Group III was the development of numerous multinucleated giant cells. The range and modal chromosome number increased from Group I to Group III, a change reflected by the higher DNA content of these cells as measured by flow cytometry. Carcinoembryonic antigen synthesis was maximal for Group III and virtually absent for Group II. The number of clonogenic cells decreased from Group I to Group III, while the proportion of nonproliferating cells calculated both by experiments using continuous labeling with tritiated thymidine, and by the primer-available alpha-DNA polymerase index, increased from Group I through Group III. Another important cytokinetic difference was that Group I had an exponential cell cycle stage distribution not seen for the other groups. Cells in Group I were easily propagated in athymic (nude) rats by s.c. injection; cells in Group II injected s.c. grew for about 30 days and then regressed spontaneously. Cells in Group III could only be grown when inoculated intracerebrally. Thus, our studies have now confirmed and extended the hypothesis that cultured human colorectal carcinomas can be separated into at least three groups on the basis of morphological differentiation, chromatin distribution, carcinoembryonic antigen production, cytokinetic properties, and xenograft propagation. Perhaps this classification is just the tip of the iceberg, and future studies will determine the existence of additional groups or subgroups on the basis of other markers. However, at present it appears established that malignant cells with a common histological origin in the gut express their phenotypic potential in a sufficiently discrete manner as to permit their classification into distinct biological groups. Thus, the stage is set for extrapolating this in vitro classification for an in vivo segregation of human colorectal tumors into categories with specific properties and diverse prognosis.

Animals↗
PubMed1983

[Drug concentrations in blood, synovial fluid, synovial membrane, periarticular bone, muscle and adipose tissue in patients with rheumatoid polyarthritis receiving a single intramuscular injection of ketoprofen or acetylsalicylic acid (3 hours after the injection)].

The therapeutic activity of antiinflammatory agents in rheumatic joint disease is related to their presence at the target site of action, i.e. the joints. Tissue concentrations of such agents have been previously determined in patients with rheumatic disorders under long-term treatment with acemetacin and indomethacin (Köhler et al., 1981). The purpose of the present study was to determine concentrations of ketoprofen and acetylsalicylic acid in blood as well as synovial fluid, synovial membrane and periarticular bone and adipose tissue, three hours after administration of a single dose. Drug concentrations found in each of these tissues following a single intramuscular injection were sufficient to ensure therapeutic efficiency.

Adipose Tissue↗
PubMed1983

[Surface glycoproteins of normal and malignant leukocytes].

This study aimed to evaluate the molecular weight distribution patterns and the quantitative expression of surface glycoproteins (S-GP) of various differentiation stages of human leucocytes. S-GP were first exposed by treatment with neuraminidase; subsequently they were labelled by galactose-oxidase treatment followed by reduction with 3H-sodium borohydride. Labelled S-GP were separated on polyacrylamide gels in the presence of SDS and were visualized by means of fluorography. A total of 8 major S-GP bands with apparent molecular weights of 230 000, 215 000, 200 000, 185 000, 175 000, 150 000, 125 000 and 110 000 daltons were identified. All of these S-GP were already expressed at the level of pluripotent myelopoietic stem cells but different in their relative expression during further cellular maturation.

B-Lymphocytes↗
PubMed1983

Distinct lymphoblastic and myeloblastic populations in TdT positive acute myeloblastic leukemia: evidence by double-fluorescence staining.

Double-immunofluorescent staining for the enzyme terminal deoxynucleotidyl transferase (TdT) as a marker of primitive lymphoblasts, and for the VIM-D5 antigen as a differentiation antigen of the myeloid system gave direct evidence for distinct lymphoblastic and myeloblastic populations (mixed leukemic cell populations) in seven patients with acute leukemia. The percentage of malignant TdT positive cells contributing to a leukemic cell bulk with unequivocal signs of myeloid origin was between 10 and 80%. A defect at the level of a common progenitor cell giving rise to both the TdT and the VIM-D5 positive blast cell population is discussed.

Antibodies, Monoclonal↗
PubMed1983

Quantitative determination of diphenhydramine and orphenadrine in human serum by capillary gas chromatography.

Diphenhydramine has been in medical use for 35 years as an antihistamine and hypnotic. We evaluated the pharmacokinetic parameters, which are not only important for disposition studies, in the serum of 10 volunteers who received a single dose of 31 mg diphenhydramine. For this purpose a suitable capillary GC-method was developed, which has a detection limit of 2 micrograms/l (serum); the calibration curve is linear between 2.5 and 120 micrograms/l, the reproducibility is always better than 3.6% and the average recovery is about 100.1%. The combination of a relatively non-polar extraction solvent, a selective detector (N-FID) and a fused silica, bonded-phase capillary column led to a more rapid sample clean-up procedure (no back-extraction needed) and is sensitive and specific enough for the quantitative determination of diphenhydramine, orphenadrine or other ethanolamines in human serum.

Chromatography, Gas↗
PubMed1983

Immunotherapy of cancer: a critical review.

During the last decade immunotherapy for human cancer has been investigated in a remarkable number of clinical trials. To date, no significant advantage has been found compared to other forms of cancer treatment. However, promising results of recent trials require further confirmation. Knowledge of immunotherapeutic modalities, dosages and timing for an effective treatment, as well as criteria of the patients' condition remain unsolved.

BCG Vaccine↗
PubMed1983

Interleukin-2 production in continuous culture.

The increasing interest in the generation of lectin or antigen-activated (human) T cells by means of Interleukin-2 (TCGF) has led to numerous attempts to produce this substance. The simplest procedure is to use conditioned medium (CM) from IL-2 producing primary cells or cell lines with considerable activity. We describe a method of continuous CM-production in a 2-litre fermentation apparatus using a primate lymphoid cell line (MLA 144) which excretes IL-2 spontaneously. It was possible to harvest large amounts of homogeneous, lectin free material with similar production rates under different culture conditions. The activity of our CM was determined in various specific systems and proven to be comparable to that of supernatants of lectin-stimulated human primary lymphocytes.

Animals↗
PubMed1983

Multistage tumor development in the human esophagus - the first identification of cocarcinogens of the tumor promoter type as principal carcinogenic risk factors in a local life style cancer.

An experimental analysis is described which demonstrates that the epidemiologically established high rate of esophageal cancer among blacks and creoles in Curacao most likely is the result of a multistage process involving initiators and promoters. As part of local lifestyle, the group at risk utilizes for various purposes plant parts of an indigenous bush Croton flavens L. ("Welensali"). Moreover they consume, as an everyday beverage, a "bush tea" made from the leaves of the bush. The roots, leaves and tea are shown to contain a multitude of irritant croton factors which are characterized as diterpene esters of the tigliane type. In mouse skin these exhibit strong promoting activity comparable to that of TPA. As the latter, also the croton factors isolated, show no solitary carcinogenic activity. One cup of Welensali tea contains the equivalent of about 12-times the irritant dose of croton factor F1; in addition, the equivalent of about 1.4-times the irritant dose 50 of the corresponding "cryptic" promoter F1-20-decanoate is present. These amounts are considered sufficient to maintain chronic irritation of the esophagus as an important element of co-carcinogenesis, especially of tumor promotion. Also, persons at risk in Curacao have been exposed at times previously to certain initiators. Mice treated by an initiation/promotion protocol with DMBA (or other initiators) and TPA develop tumors of the forestomach. Therefore, esophageal cancer on Curacao may be considered the first case for cocarcinogens of the tumor promoter type being principal risk factors in a life style cancer.

Animals↗