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Biomedical subjects

M Loken

Publications and source records attributed to M Loken.

At least 19 recordsLinked to original sources
PubMed2006

CTLA-4 blockade by a human MAb enhances the capacity of AML-derived DC to induce T-cell responses against AML cells in an autologous culture system.

BACKGROUND: Cells from AML patients can differentiate into the phenotype of DC when cultured with GM-CSF and IL-4. Such cytokine-treated AML-derived DC (AML-DC) can stimulate autologous T cells. In this study we examined whether an anti-CTLA-4 MAb (MDX-010) could enhance the generation of autologous anti-AML T cells. METHODS: MAb MDX-010 was added to AML PBMC cultures in the presence of GM-CSF and IL-4, a previously reported AML-DC culture method of generating anti-AML T cells. T-cell activation and proliferation were examined thereafter. RESULTS: Addition of MDX-010 to GM-CSF/IL-4-conditioned AML-DC cultures induced a mean seven-fold increase in the numbers of autologous T cells compared with cultures without MDX-010 (P < 0.007). T cells stimulated by AML-DC with CTLA-4 blockade were significantly more cytotoxic towards autologous AML cells than those without MDX-010 (42 +/- 23% vs. 26 +/- 15%, E:T ratio of 20). T cells stimulated by AML-DC with CTLA-4 blockade had significantly greater proportions of T cells producing IFN-gamma in response to autologous AML cells than those cultured with AML-DC alone (10.7 +/- 4.7% vs. 4.5 +/- 2.4% for CD4+ IFN-gamma+ CD69+ and 9.8 +/- 4.1% vs. 4 +/- 2.1% for CD8+ IFN-gamma+ CD69+ with or without MDX-010; n = 7; P < 0.007, P < 0.003, respectively). DISCUSSION: CTLA-4 blockade enhances the activity and numbers of AML-reactive T cells that can be stimulated by autologous AML-DC and may enhance the efficacy of adoptive immunotherapy of AML.

Antibodies, Monoclonal↗
PubMed2001

Comparison of multidimensional flow cytometry with standard morphology for evaluation of early marrow response in pediatric acute lymphoblastic leukemia.

PURPOSE: We compared multidimensional flow cytometry (MDF) with morphology in evaluating early marrow response to induction chemotherapy in pediatric ALL. METHODS: Chemotherapy response was determined by standard morphology or by MDF assessed by residual leukemic cell percentage remaining in the marrow on days 7, 14, and 28 of induction. Bone marrow response was classified as M3 (>25% leukemic blasts) or M1/M2 (< or = 25% leukemic blasts). Multidimensional flow cytometry evaluation was compared with that of standard morphology. Available day-7 and day-14 marrow slides were also reevaluated by a single pathologist without patients' clinical information. RESULTS: Of 46 day-7 specimens, eight (17%) had discordant MDF and morphologic results (P < 0.001), including six classified as M3 by morphology but were M1/M2 by MDF, and two were classified as M3 by MDF but were M1/M2 by morphology. Of 24 day-14 bone marrow specimens, five (20.5%) were discordant (P < 0.001), including two classified as M3 by morphology but were M1/M2 by MDF, and three were classified as M3 by MDF but were M1/M2 by morphology. Reevaluation of the blinded day-7 and day-14 marrow slides yielded discordance between repeated pathology readings of 11% (P < 0.001) and 6% (P = 0.04), respectively. CONCLUSION: Our data show significant discordance between the morphologic and MDF evaluation of early marrow response. Early response to therapy is a significant prognostic indicator in pediatric acute lymphoblastic leukemia and is used to alter subsequent treatment; thus, precise assessment of response is important. A larger comparison of MDF with morphology for the evaluation of early response, including correlation with clinical outcome, is warranted.

Adolescent↗
PubMed1999

Haemopoietic reconstitution by donor-derived myelodysplastic progenitor cells after haemopoietic stem cell transplantation.

A 50-year-old woman who was retrospectively diagnosed with an early asymptomatic myelodysplastic syndrome (MDS) served as a haemopoietic stem cell donor for her HLA-identical sister who had chemotherapy-refractory non-Hodgkin's lymphoma. The MDS of the donor was classified as refractory anaemia (RA) and cytogenetically characterized by deletion of the long arm of chromosome 20 [del(20q)]. Donor cell engraftment in marrow and peripheral blood was analysed over a period of 5 months after transplant using conventional cytogenetics, fluorescence in situ hybridization, and variable number of tandem repeats. Neutrophil counts >0.5 x 109/l and platelet counts >20 x 109/l were reached promptly on days 12 and 24, respectively. Throughout the period of observation the percentage of cells with the del(20q) abnormality in the recipient's marrow and peripheral blood was comparable to the proportion of these cells in the donor. These data indicate that the abnormal clone was capable of homing to the marrow, proliferating, differentiating, and therefore contributing to haemopoiesis in a relatively efficient manner. This implies that MDS progenitor cells may not have homing and growth deficiencies, a finding that has particular relevance for autologous transplantation in MDS patients where tumour cells potentially contaminate the graft.

Adult↗
PubMed1998

Isolation of CD34+ cells from blood stem cell components using the Baxter Isolex system.

The CD34 antigen is expressed by human hematopoietic progenitor and stem cells. These cells are capable of reconstituting marrow function after marrow-ablative chemo-radiotherapy. Several different technologies have been developed for the separation of CD34+ cells from bone marrow or peripheral blood stem cell (PBSC) components. We used an immunomagnetic separation technique to enrich CD34+ cells from PBSC components in anticipation of autologous transplantation for patients with B lymphoid malignancies. Twenty-nine patients enrolled on this study and received mobilization chemotherapy followed by G-CSF. Of these, 21 achieved a peripheral blood CD34+ cell level of at least 2.0 x 10(4)/l required by protocol for separation of the stem cell components. A median of three components per patient was collected for processing. The average CD34+ cell concentration in the components after apheresis was 1.0 +/- 1.2%. After the CD34+ cell selection, the enriched components contained 0.6 +/- 0.6% of the starting nucleated cells. The recovery of CD34+ cells, however, averaged 58.4 +/- 19.2% of the starting cell number, with a purity of 90.8 +/- 6.5%. Overall depletion of CD34- cells was 99.96 +/- 0.06%. Nineteen patients were treated with marrow-ablative conditioning regimens and received an average of 6.2 +/- 2.0 x 10(6) CD34+ cells/kg body weight. These patients recovered to an ANC >0.5 x 10(9)/l at a median of 11 days (range 8-14), and platelet transfusion independence at a median of 9 days (range 5-13). Four patients died of transplant-related complications or relapse before 100 days after transplantation. No patient required infusion of unseparated cells because of failure of sustained bone marrow function. These data demonstrate that peripheral blood-derived CD34+ cells enriched by use of an immunomagnetic separation technique are capable of rapid engraftment after autologous transplantation.

Adult↗
PubMed1993

The influence of image resolution on the positron emission tomographic measurement of caudate glucose consumption.

The aim of this study was to investigate the influence of image resolution on (a) relative and absolute values of caudate glucose consumption (rCMRGlc) determined by positron emission tomography (PET), and (b) the detection of significant differences in these metabolic values between groups of subjects. For this purpose, raw data of cerebral accumulation of fluorine-18 fluorodeoxyglucose (FDG) obtained in 11 normal subjects and in nine patients with unilateral thalamic infarction were reconstructed using filtered backprojection with four different cut-off frequencies (CFs), yielding images with a transaxial resolution of 5.7, 7.1, 8.9 and 11 mm (full-width at half-maximum; FWHM). Absolute values of caudate rCMRGlc decreased significantly by more than 30% over the range of image resolutions studied. Bilateral ratios of caudate rCMRGlc were insensitive to variations in image resolution. Levels of significance assessing the differences in mean metabolic values between patients and controls were all below 0.01. They were, however, slightly better at image resolutions of 7.1 and 8.9 mm than at a resolution of 5.7 mm. These data indicate (a) that relative values of rCMRGlc are better suited to compare quantitative results from different PET cameras than are absolute values, and (b) that the CF used for the filtered back-projection exerts a small but not negligible influence on levels of significance assessing differences in metabolic values between groups of subjects.

Adult↗
PubMed1992

On the influence of spatial resolution and of the size and form of regions of interest on the measurement of regional cerebral metabolic rates by positron emission tomography.

Factors that affect the accuracy of the positron emission tomographic (PET) quantification of cerebral metabolic rates include the spatial resolution of the employed imaging device and the method used for extraction of regional metabolic values from the PET data set. The present article reviews (i) how and to what extent these two factors are presumed to influence the measurement of absolute values of cerebral metabolic rates and their ratios, and (ii) whether and how these factors may affect comparisons of regional metabolic rates between groups of subjects.

Brain↗
PubMed1992

Regional cerebral glucose consumption measured by positron emission tomography in patients with Wilson's disease.

Using positron emission tomography (PET), the regional cerebral metabolic rate of glucose consumption (rCMRGlc) was measured in 14 patients with Wilson's disease (WD) and 23 normal subjects. In WD patients, cerebellar, striatal and--to a lesser extent--cortical and thalamic rCMRGlc were significantly decreased compared with controls. Striatal rCMRGlc was significantly reduced in those 4 patients who had recently started decoppering therapy as compared with striatal rCMRGlc measured in those 10 patients with longer duration of medication. Caudate rCMRGlc correlated significantly with various signs of extrapyramidal dysfunction. Cerebellar, thalamic and cortical rCMRGlc correlated significantly with the severity of pyramidal signs. These data indicate that the PET measurement of rCMRGlc may be a useful tool to evaluate cerebral involvement in WD and to monitor the response to treatment.

Adult↗
PubMed1990

Locus of information in words and the right visual field effect.

The right visual field (RVF) advantage found for the identification or classification of words has usually been interpreted as evidence for left hemisphere language functions. It has more recently been explained as the result of the fact that the most informative part of the word, presumably the beginning, is in a region of better visual acuity. It is not clear from existing evidence that the beginnings of words are in fact more informative. The present study assessed the locus of information in words by deleting either the initial or terminal one or two letters. Subjects were required to generate a completion. Regardless of whether subjects were scored as correct for generating the original target word (as would be appropriate in a naming study) or for producing any legitimate word (as would be appropriate for a lexical decision study), the results indicated that most words have more information in the initial letters. Nevertheless, there are exceptions to this rule, and some words have more terminal information. Equal numbers of words with more initial information and with more terminal information were selected for two visual field studies in order to assess the effect of the locus of information on visual laterality. In neither a lexical decision study nor a naming study did locus of information affect the commonly observed right visual field superiority. Thus the distribution of information is not likely to be a major confounding variable in laterality studies employing horizontally presented words.

Adolescent↗
PubMed1987

Grading of reflux by radionuclide cystography.

Over a three-year period, radionuclide cystography (RC) was performed on 145 patients. Of these, 31 nephroureteral units in 25 patients demonstrated vesicoureteral reflux by RC and also by radiographic cystography (XC). The RC and XC studies were performed within three months of one another. The grading of reflux was determined by RC and then compared with that of XC using the criteria for grading as established by the International Reflux Study Committee (IRSC). Of 18 nephroureteral units in 14 patients with grade II reflux by XC, 14 were similarly graded by RC (78%). Of five nephroureteral units in five patients with grade III reflux by XC, the correlation by RC was 100%. However, when grades II and III were combined into a single category of low-grade reflux, the correlation achieved between the two cystographic techniques was 100%. Of five nephroureteral units in four patients with grade IV reflux by XC, the correlation was 60%, and in three units in two patients with grade V reflux the correlation was 100%. When grades IV and V are combined into a category of high-grade reflux, a correlation of 100% is achieved. When the reflux is graded into the five IRSC categories, the overall unequivocal correlation between the two studies is 80%. However, when only two categories are used (low grade = grades II and III, and high grade = grades IV and V), a correlation of 100% is obtained.

Adolescent↗
PubMed1985

Comparison of the distribution and binding of monoclonal antibodies labeled with 131-iodine or 111-indium.

The distribution of two monoclonal antibodies with reactivity against human leukemia/lymphoma associated antigens (BA-1 antibody) and carcinoembryonic antigen (202 antibody) when labeled with 131I or 111In was studied in normal Balb/c mice. The BA-1 antibody of the IgM subclass was labeled with 131I by the micro iodine monochloride method at a 12:1 molar ratio and with 111In by the cyclic DTPA anhydride method at a 10:1 molar ratio. In vitro, the 131I-labeled BA-1 antibody bound 35.5% to 10(7) KM-3 leukemic cells while the 111In-labeled BA-1 antibody bound 29.9% to the same number of KM-3 cells. In vivo, the 111In-labeled BA-1 antibody showed a higher accumulation in liver, spleen, and kidney than the 131I-labeled BA-1 antibody. The 202 antibody of the IgG1 subclass was labeled with 131I at a 5:1 molar ratio and with 111In at a 7:1 molar ratio. In vitro, the 131I-labeled 202 antibody bound 30.9%, 27.4%, and 30.0% to 10(7) CO-112, WIDR, and LS-174T colon cancer cells, respectively. The 111In-labeled 202 antibody bound 20.5%, 30.2%, and 33.6%, respectively to the same number of colon cancer cells. In vivo, the 131I-labeled 202 antibody showed a higher tissue to blood ratio in liver, spleen, and kidney than the 111In-labeled 202 antibody. The data indicate that the relative distribution of 131I-labeled versus 111In-labeled monoclonal antibody may depend on the immunoglobulin subclass of the antibody and the molar ratio used in labeling.

Animals↗
PubMed1979

False-positive 111In-labeled leukocyte scan in cystic fibrosis.

A false-positive 111In-labeled leukocyte scan was obtained in a girl with cystic fibrosis and infection. There was focal accumulation of 111In activity in the abdomen and marked pulmonary uptake. Surgical exploration and postmortem examination revealed no abdominal abnormality. The abnormal activity was apparently due to swallowed sputum which contained labeled leukocytes. Broader clinical implications are discussed.

Abdomen↗