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Biomedical subjects

M R Halie

Publications and source records attributed to M R Halie.

At least 91 records · Page 5Linked to original sources

Small cell lung cancer and the influence of chemotherapy on CFUcs in bone marrow.

To determine the optimal moment for the harvesting of bone marrow for autologous transplantation, the authors did serially colony forming units in culture (CFUc) counts in a group of 42 patients with small cell lung cancer (SCLC) before and after remission induction chemotherapy and subsequent maintenance chemotherapy. Disease stage did not influence the CFUc count except in patients with bone marrow metastases; this resulted in either abnormally low or abnormally high CFUc counts, probably dependent on the degree of invasion. After 2 courses of induction chemotherapy, the number of CFUcs was 3.1-fold higher than before therapy. After 4 courses, the CFUcs number was comparable to the pretreatment value. An inverse correlation was found between the degree of hematologic toxicity (expressed as leucocytes count) and the increase of CFUcs after induction chemotherapy. The number of CFUcs decreased during prolonged chemotherapy to low levels after 1 year. Harvesting of bone marrow is probably done best shortly after induction chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗

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↗

Total polyamines and their non-alpha-amino acid metabolites simultaneously determined in urine by capillary gas chromatography, with nitrogen-phosphorus detector; and some clinical applications.

A capillary gas-chromatographic method with nitrogen-phosphorus detection is used here to simultaneously determine 1,3-diaminopropane, putrescine, cadaverine, spermidine, spermine, isoputreanine , putreanine , and N-(3-aminopropyl)-N'-(2-carboxyethyl)-1,4- diaminobutane in urine. After acid hydrolysis the compounds are isolated by adsorption onto silica gel and converted into their methyl-heptafluorobutyryl derivatives. We give quality-control data and age-dependent values for urinary excretion of these analytes by 76 apparently healthy controls. Circadian rhythmicity in the excretion of spermidine and (especially) isoputreanine was established and is discussed in the light of its implications for monitoring therapy of cancer. Investigation of menstrual-cycle-dependent diurnal variation in one normal woman showed no distinct, consistent fluctuations. We applied the method to monitor (by use of 24-h urine specimens) an uncomplicated, normally progressing pregnancy, a patient with metastatic melanoma being treated with cytostatic drugs, and (in more detail) the treatment of a patient with high-grade non-Hodgkin lymphoma.

Adolescent↗

The heterogeneity of follicular follicle center cell tumors. II. Clinical follow-up of 30 patients.

The Kiel classification for the histology of malignant lymphomas distinguishes the group of follicular lymphomas as low-grade malignancies. Clinically, this proves to be a heterogeneous group. With the aim of establishing parameters giving indications for the prognosis of the patient, a retrospective analysis was made of 30 patients with a histologic diagnosis of follicular follicle center cell tumor (FCC). Neither the immunologic markers of the cells nor the stage of dissemination have prognostic significance for survival. On the basis of the predominating neoplastic cell type, a cytologic subdivision of the lymphomas was made, characterizing the following subgroups: SCC (small centrocytes with occasional centroblasts), CBCC/A (centrocytes with several centroblasts), and CBCC/B (centrocytes with many centroblasts), SLCC (small and large centrocytes), SLCB (small and large centroblasts). The actuarial survival of the total group of 30 patients was 66% after 5 years, but the survival in the cytologic subgroups ranged from 100% in group SCC to 0% in group SLCB. Comparing the groups SCC and CBCC/A with CBCC/B and SLCB gave a significantly worse prognosis for the groups with an increased number of centroblasts (i.e., CBCC/B and SLCB). Therefore it seems justified to treat patients with a predominance of centroblasts aggressively with the aim of reaching a complete remission.

Adult↗

The heterogeneity of follicular center cell lymphomas. I. Cytohistologic, immunologic, and enzymehistochemical aspects.

Histologic material from 44 patients with follicular center cell lymphomas with a follicular growth pattern was divided into five groups on the basis of the predominating neoplastic cell type(s), i.e., small centrocytes with occasional centroblasts (SCC), centrocytes and few (CBCC/A) or many (CBCC/B) centroblasts, small and large centrocytes (SLCC), and small and large centroblasts (SLCB). Histologic, immunologic, and enzymehistochemical parameters as observed in these groups were compared, and follow-up material and material obtained during staging procedures were studied. Immunologic and enzymehistochemical findings confirmed both the B-cell origin and the neoplastic nature of the lymphomas, but did not yield relevant differences between the various groups. The groups with a predominance of small centrocytes or of small centrocytes and centroblasts showed the most prominent follicular growth and early dissemination to bone marrow and spleen. Histologic transformation in these groups was characterized by an increase in the number of centroblasts and a more diffuse growth pattern. The groups composed of small and large centrocytes or centroblasts tended to a more diffuse growth and had later dissemination and no histological transformation.

Acid Phosphatase↗

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↗

Classification of immature and mature cells of the neutrophil series using morphometrical parameters.

Quantitative morphological data of six classes of immature and mature cells of the neutrophil series of the bone marrow of normal persons were used for statistical classification experiments (myeloblasts, promyelocytes, myelocytes, metamyelocytes, bands and segments). On each cell, parameters were measured directly from the image or calculated from the shape of the density histogram or the counting densitogram using a Texture Analysis System (E. Leitz, Wetzlar, Germany). The parameters were analyzed with the interactive statistical pattern recognition system ISPAHAN. One half of the data were used as a learning set and the other half as the test set. The parameters were compared according to their performance in discrimination between the classes, alone and in combinations. Parameters not contributing to an improvement of the discrimination were disregarded. Eleven parameters were selected and used for classification by two different methods: a stepwise and a "one-shot" method. Stepwise classification resulted in a 79% correct classification rate. Most errors occurred between cell classes in neighboring stages of maturation. In 96% of all cases the computer classification was either in accordance with that of the technician or with a cell class of a neighboring maturation stage. One step classification by the computer was in agreement with the technicians in 82% of the cases. For 98% of the cells the computer classification was either in accordance with that of the technician or with a cell class of a neighboring maturation stage. The data set was collected by two technicians, operating independently. Differences in their interpretation of the maturation stage were found by comparing the performance of classifiers based on both cell samples. Since the images of the cells were not available for reexamination, the causes of disagreement in classification between the technicians and between computer and technicians could not be evaluated.

Biometry↗

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↗

Lymphocyte characteristics and function in paroxysmal nocturnal haemoglobinuria.

In six patients with paroxysmal nocturnal haemoglobinuria (PNH) lymphocyte studies were performed to investigate whether the observed immunological dysfunction could be ascribed to a defect in lymphocytes as result of the PNH characteristics, or to an imbalance between T-cell subsets. The PNH characteristics were studied by means of the effect of serum and acidified serum on Indium111-oxine labelled lymphocytes. No increase in release of Indium111-oxine was found when lymphocytes were exposed to acidified sera. Thus a complement mediated lymphocyte lysis in PNH could not be demonstrated. T-cells were defined by monoclonal antibodies, directed at total T-cells (OKT3), helper T cells (OKT4) and suppressor/cytotoxic T-cells (OKT8). In two of the six patients a decreased proportion of OKT3 cells was found, while a significantly depressed ratio of OKT4/OKT8 cells was present in the whole group. No obvious correlation was found between a functional assay - the concanavalin-A suppressor cell activity - and the ratio of OKT4/OKT8 positive cells. It is concluded that the PNH characteristics could not be demonstrated in the lymphocytes; and that the immunological dysregulation in PNH may be ascribed to an imbalance of T-cell subsets, while a decreased number of monocytes, defined by the monoclonal antibody OKM1, may contribute to this defect.

Antibodies, Monoclonal↗

Plasma spermidine concentrations as early indication of response to therapy in human myeloma.

Eighteen patients with melphalan refractory myeloma were treated with vindesine and prednisone. Plasma spermidine concentrations were measured by radioimmunoassay before and after a single vindesine injection. Seven patients showed a significant rise of plasma spermidine after vindesine and five of these showed a clinical response on further evaluation. Of the 11 patients who did not show raised spermidine concentrations, 10 did not respond to the therapy. The correlation between clinical response/rise of spermidine and between non-response/no rise of spermidine was statistically significant (p less than 0.05). Pretreatment spermidine concentrations did not distinguish those who responded to treatment nor did they differ in patients and controls.

Antineoplastic Agents↗

In vitro effects of lithium on granulocyte colony formation in normal men, in hematological disorders and in small-cell carcinoma of the lung.

In a two-layer soft agar system the indirect effect of lithium via colony stimulating factor and/or its direct effect on the granulocyte progenitor cells of bone marrow of healthy volunteers, patients with different hematological disorders, and with small-cell carcinoma of the lung, were evaluated. A significant increase in the number of myeloid colonies was found with a concentration of 0.1 mmol/l lithium carbonate in the feeder layer in all patient groups except those with overt acute myelomonocytic leukemia (AMMoL). No effect was seen if lithium was added to the overlayer. The increment of colonies cultured with lithium in the feeder layer was directly related to the initial number of colonies cultured without lithium (correlation coefficient 0.96). The former colonies had a 1.5- to 2-times larger size than the latter, and cell cycle analysis showed a significant increase in the percentage of cells in S, G2 and M phase. No such effects were seen in AMMoL on the number and size of the colonies and the characteristic growth pattern. In this study lithium has an indirect effect on the number and size of bone marrow myeloid colony formation in healthy people as well as patients with different hematologic cell disorders and small-cell carcinoma of the lung, while no such influence was observed with overt AMMoL patients.

Agranulocytosis↗

Fc gamma receptors on lymphocytes from normal donors and patients with lymphoproliferative diseases. Influence of incubation conditions.

The antibody-coated human erythrocyte and the antibody-coated ox erythrocyte rosette assays (EAHu and EAOx) were compared to detect Fc gamma receptors on human peripheral blood lymphocytes. Two incubation conditions were examined: 1 h at room temperature and overnight at 4 degrees C. In healthy persons, in patients with Hodgkin's disease and in patients with non-Hodgkin lymphoma (NHL) the mean percentage of EAHu-rosette-forming cells (EAHu-RFC) increased significantly when the incubation was carried out overnight at 4 degrees C instead of 1 h at room temperature. This increase was caused by Fc gamma receptor-bearing T cells. In the case of EAOx-RFC only a slight increase was found. The percentage of EAHu-RFC and EAOx-RFC differed significantly in the healthy group after the overnight incubation and in the NHL group after the 1-hour incubation. When comparing the mean percentage of EA-RFC in the patient groups with that of the healthy persons significant increases were observed: EAHu-RFC in patients with Hodgkin's disease in the overnight incubation and EAOx-RFC in patients with Hodgkin's disease and NHL in both incubation conditions. In patients with chronic lymphocytic leukemia (CLL, B-cell type) the mean percentage of EAHu-RFC was very low, however that of EAOx-RFC was moderate to high. It is concluded that in the two rosette assays the antigen-antibody complexes may have different avidities to different lymphocyte subpopulations, and that incubation conditions may have an influence on this avidity.

Animals↗

Relevance of morphometric parameters for the classification of normal white blood cells.

An interactive morphometry system (Leitz T.A.S.) was used to extract 39 parameters from 1506 cells of five normal WBC classes. The data set was split in a learning set and a test set, and the value of each single parameter and of combinations of parameters was assessed with the interactive pattern recognition system ISPAHAN. A combination of nine densitogram parameters gave a correct classification in 92.6%; adding four geometrical and seven counting densitogram parameters improved this to 98.5%. It appeared that simple measurements are sufficient for a correct differentiation into the normal white blood cell types. In a pilot study fo 40 normal myeloid bone marrow cells of four classes a correct discrimination between mature and immature cells was reached in 93%. Extraction of parameters with the T.A.S. and their subsequent evaluation with ISPAHAN appeared to be an efficient method of white blood cell classification probably including immature cell types.

Autoanalysis↗