Biomedical subjects

L C Strauss

Publications and source records attributed to L C Strauss.

34 records · Page 2Linked to original sources

PubMed1987

Antigenic analysis of hematopoiesis. VI. Flow cytometric characterization of My-10-positive progenitor cells in normal human bone marrow.

We have previously shown [1] that the anti-My-10 murine monoclonal antibody detected an epitope of a 115-kDa glycoprotein expressed specifically on KG-1a leukemia cells and a small subset of normal human bone marrow cells. This My-10+ marrow cell subset was shown to contain a highly enriched population of morphologic blast cells and hematopoietic colony-forming cells [1]. In this report, My-10+ cells were characterized, by flow cytometry, as an approximately 1% subpopulation of normal human bone marrow cells. My-10+ cells were slightly larger than lymphocytes and agranular, as determined by their fluorescence-activating cell sorting (-er) (FACS) light-scattering properties. In two-color immunofluorescence experiments, My-10+ cells coexpressed the HLA-DR antigen. However, there was no detectable cellular coexpression of My-10 with either the Leu 1-5, 7, 9, 11, 15, M3, or My-18 antigens. There was an average of approximately 50,000 My-10 molecules per My-10+ marrow cell. This provides further evidence that the My-10 molecule is expressed, at relatively low levels, selectively on early human marrow cells but not on mature lymphohematopoietic cells.

Antibodies, Monoclonal↗

PubMed1986

Analysis of histiocytosis X infiltrates with monoclonal antibodies directed against cells of histiocytic, lymphoid, and myeloid lineage.

Surface markers expressed on histiocytosis X (HX) cells were studied using 18 monoclonal antibodies (McAbs) and an in situ indirect immunoperoxidase technique. Specimens of skin (five biopsies from three cases) and lymph node (one case) were studied. Our study confirmed previous findings of an OKT6+ HLA DR+ Leu 3a+ phenotype of HX cells in skin and indicated that lymph node HX cells can also have this phenotype. A mixture of cells expressing T markers/T subset, monocyte/macrophage, and killer/natural killer (K/NK) markers was also present in two cases. However, one case with an aggressive course showed no detectable HNK 1+ (K/NK) or Leu 2A (suppressor) cells in the cutaneous infiltrates and no detectable HNK 1+ lymphocytes in an affected lymph node. The significance of these findings in relation to prognosis and therapy is discussed.

Antibodies, Monoclonal↗

PubMed1986

Development of a simplified counterflow centrifugation elutriation procedure for depletion of lymphocytes from human bone marrow.

Graft-versus-host disease (GVHD) remains a major complication of allogeneic bone marrow (BM) transplantation. Techniques that effectively purge BM of mature T lymphocytes should reduce the incidence of GVHD and improve survival. We have developed a simplified, two-flow rate, fixed rotor speed counterflow centrifugation-elutriation (CCE) procedure that reproducibly depletes 99% of lymphocytes from Ficoll-Hypaque(F/H)-separated BM or BM buffy-coat. Two predetermined flow rates (24 and 28 ml/min) were used to purge small and intermediate-to-large lymphocytes, respectively, whereas faster sedimenting cells were recovered at the termination of the run. Lymphocyte depletion was substantiated by pan-T monoclonal antibody analysis as well as by complete loss of responsiveness to alloantigens and mitogens. Despite the lack of mature T cells, the depleted marrow fraction retained lymphoid colony-forming ability. Lymphocyte-purged marrow was obtained in high yield (72%), and retained high viability (greater than 97%) and hematopoietic colony-forming ability (greater than 99%). The ratio of total myeloid/erythroid colony-forming cells to T lymphocytes was 73-fold higher in the lymphocyte-depleted fraction than in unseparated BM. We concluded that a two-step CCE procedure can be used to rapidly deplete lymphocytes from both F/H-separated and buffy-coat BM inocula without altering hematopoietic capacity as measured by the in vitro clonogenic assays. It may be possible to adapt this procedure to the separation of the large number of marrow cells required for human BM transplantation.

Antibodies, Monoclonal↗

PubMed1986

Two primary brain tumors in one child.

We studied a 4-year-old boy with symptoms and signs of a posterior fossa tumor. CT showed two separate intracranial tumors: a fourth ventricle choroid plexus papilloma and a frontal subependymal giant-cell astrocytoma. This case emphasizes that, even in the absence of special genetic predisposition to CNS tumors, two separate intracranial masses may not represent CSF metastasis of a single primary tumor.

Astrocytoma↗

PubMed1986

Antigenic analysis of hematopoiesis. IV. The My-11 hematopoietic cell surface antigen is expressed by myelomonocytic and lymphoid, but not erythroid, progenitor cells.

The anti-My-11 murine monoclonal antibody reported on in this work identifies a KG-1a cell surface glycoprotein with apparent molecular mass of 210,000 daltons. Peripheral blood B-lymphocytes, and a novel subset of T-lymphocytes (not coinciding with helper or cytotoxic subsets) express My-11 antigen; granulocytes, red cells, and platelets are antigen negative. In normal bone marrow, lymphoid progenitors (TdT positive) and most granulocyte-monocyte progenitors express My-11, but erythroid and multilineage progenitors are My-11 negative. Approximately half of acute leukemia blast cell specimens are My-11 positive. The My-11 antigen distinguishes between lymphohematopoietic cells on the basis of lineage, and assists in the purification of hematopoietic progenitor cells and the subclassification of leukemias and normal lymphocytes.

Antibodies, Monoclonal↗

PubMed1986

Antigenic analysis of hematopoiesis. V. Characterization of My-10 antigen expression by normal lymphohematopoietic progenitor cells.

The My-10 glycoprotein is an hematopoietic cell surface antigen expressed specifically by undifferentiated (blast) cells, constituting 1%-4% of normal adult bone marrow leukocytes. We used several immunological and in vitro culture methods to analyze the expression of this unique antigen on a variety of lymphohematopoietic progenitor cells. Colony-forming cells (CFC) for granulocyte-monocyte colonies (CFC-GM) and erythroid colonies (BFU-E) were predominantly My-10 positive. CFC with higher proliferative potential were more strongly My-10 positive than CFC with lower proliferative potential, and those for mixed-lineage and blast cell colonies were even more uniformly My-10 positive. Cells maintaining CFC-GM number in short-term marrow culture (pre-CFC) were found to be My-10 positive, as were lymphoid precursors defined by their content of intranuclear terminal deoxynucleotidyl transferase. More mature erythroid precursors (CFU-E) were heterogeneous for antigen expression and lost My-10 antigen progressively, in parallel with advancing maturational stage. The My-10 antigen permits rapid identification and purification of hematopoietic progenitor cells for further study or potential clinical application. The disappearance of the My-10 antigen, moreover, may be a probe for differentiation-linked cellular events.

Antigens, Surface↗

PubMed1985

Response of a recurrent choroid plexus tumor to combination chemotherapy.

Choroid Plexus tumors are rare. Surgery and biopsy is diagnostic, and radiotherapy has been used as the treatment of choice for choroid plexus carcinoma (CPC) and recurrent choroid plexus papilloma (CPP). We report the first case of CPP responding to combination chemotherapy consisting of cisplatin, bleomycin and vinblastine (CBV). This chemotherapy regimen should be considered for future trials in patients with choroid plexus tumors and recurrence after surgery and/or radiotherapy.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1985

Localization of hematopoietic progenitor cells in tissue with the anti-My-10 monoclonal antibody.

Putative hematopoietic progenitor cells were localized in human lymphoid and nonlymphoid tissues with the use of the anti-My-10 antibody and avidin-biotin immunoperoxidase. Groups of My-10+ round mononuclear cells were evident in the splenic marginal zone near the follicular mantle. My-10+ cells were also evident in the hepatic portal triads and rare cells were seen near Peyer's patches. Except for My-10+ endothelial cells, there was no staining of the thymus, lymph node, skin, or kidney specimens.

Antibodies, Monoclonal↗

PubMed1985

Disparate differentiation in hemopoietic colonies derived from human paired progenitors.

We analyzed the differentiation of hemopoietic colonies derived from human paired daughter cells. Candidate progenitor cells were isolated by use of a micromanipulation technique from cultures of My-10 antigen-positive cord blood cells. Then nine to 36 hours later, the paired daughter cells were separated with a micromanipulator and allowed to form colonies in methylcellulose medium containing erythropoietin, phytohemagglutinin leukocyte-conditioned medium, and platelet-poor plasma. The cellular composition of the colonies was determined by differentiating all of the cells of the May-Grünwald-Giemsa-stained preparation. Of a total of 75 evaluable pairs of colonies, 35 consisted of 28 types of disparate pairs revealing nonhomologous lineage combinations. Forty pairs were homologous in lineage expression. However, the proportions of the individual cell lineages were significantly different in the members of some of the homologous pairs. Some pairs revealed significant differences in colony size. These observations are similar to those reported for murine paired progenitors and are consistent with the stochastic model of human stem cell differentiation.

Basophils↗

PubMed1984

Single cell origin of multilineage colonies in culture. Evidence that differentiation of multipotent progenitors and restriction of proliferative potential of monopotent progenitors are stochastic processes.

In this paper, we report analysis of differentiation in human hemopoietic colonies derived from a single cell. Cord blood mononulear cells and panned My-10 antigen-positive bone marrow and cord blood cells were plated in methylcellulose medium containing erythropoietin and conditioned medium. Initially, we performed mapping studies to identify candidate colony-forming cells. Subsequently, using a micromanipulator, we transferred single cells individually to 35-mm dishes for analysis of colony formation. Cellular composition of the colony was determined by identifying all of the cells in the May-Grunwald-Giemsa stained preparation. Of 150 single candidate cells replated, 63 produced colonies. The incidences of single lineage colonies included 19 erythroid, 17 monocyte-macrophage, and 9 eosinophil colonies. There were 18 mixed hemopoietic colonies consisting of cells in two, three, four, and five lineages in varying combinations. In some instances, we noted the predominance of one lineage and the presence of very small populations of cells in a second or third lineage. These results provide evidence for the single-cell origin of human multilineage hemopoietic colonies, and are consistent with the stochastic model of stem cell differentiation in man. They also indicate that restriction of the proliferative potential of committed progenitors is a stochastic process.

Bone Marrow Cells↗

PubMed1984

Acquired chromosome rearrangements, including fine interstitial deletions, in a patient with Down syndrome and monoblastic leukemia.

A female child with Down syndrome who developed acute monoblastic leukemia is reported. Anemia associated with milk leukopenia was first recognized when the patient was 14 months old. Acute monoblastic leukemia was diagnosed 1 year later; cytogenetic studies were performed on circulating leukemic cells at this time. Analysis of elongated, finely banded chromosomes revealed three structural rearrangements, including two rather subtle interstitial deletions, in addition to trisomy 21 which was representative of the patient's constitutional karyotype. The karyotype of the leukemic cells was 47,XX,+21,t(3;18)(p23;q11.2), del(7)(q31.1q31.3), del(9)(p22p24 or p21p23). The patient received no cytostatic chemotherapy and died 4 months after the diagnosis of acute leukemia was made.

Child, Preschool↗

PubMed1984

Antigenic analysis of hematopoiesis. III. A hematopoietic progenitor cell surface antigen defined by a monoclonal antibody raised against KG-1a cells.

The anti-My-10 mouse monoclonal antibody was raised against the immature human myeloid cell line KG-1a and was selected for nonreactivity with mature human granulocytes. Anti-My-10 immunoprecipitated a KG-1a cell surface protein with an apparent Mr of approximately 115 kD. We describe the binding of this antibody to human hematopoietic cell types and show that My-10 is expressed specifically on immature normal human marrow cells, including hematopoietic progenitor cells. My-10 is also expressed by leukemic marrow cells from a subpopulation of patients. Thus, this antibody allows the identification and purification of hematopoietic progenitor cells from normal human marrow and the subclassification of leukemia.

Acute Disease↗

PubMed1984

Antigenic analysis of hematopoiesis: II. Expression of human neutrophil antigens on normal and leukemic marrow cells.

The binding of five antineutrophil monoclonal antibodies AHN-1, -2, -3, -7, and -8, to normal and leukemic bone marrow cells was studied. AHN-7 bound to many granulocytic precursors, particularly myelocytes, and both lymphoid and blast cells in normal marrow, and to most but not all granulocyte-macrophage progenitors (CFC-GM). AHN-8 bound only to late (band and segmented) neutrophilic cells and not to CFC-GM. AHN-1, -2, -3 bound to morphologically identifiable neutrophil precursors, but not to (day-14) CFC-GM. Approximately half of nonlymphoid leukemia specimens were positive with AHN-1 or AHN-7; by contrast, lymphoid leukemia specimens were rarely positive. AHN-8 was rarely found on leukemic cells. These antineutrophil antibodies appear to detect distinct granulopoietic subsets and may be useful in the analysis of hematologic differentiation and in the subclassification of leukemias.

Animals↗

PubMed1983

Antigenic analysis of hematopoiesis. I. Expression of the My-1 granulocyte surface antigen on human marrow cells and leukemic cell lines.

Five monoclonal antibodies that identify the My-1 human granulocyte surface antigen were not reactive with other peripheral blood cells. These antibodies effected complement-dependent cytolysis of a large fraction of normal human marrow leukocytes. This My-1-positive marrow cell population consisted of morphologically identifiable granulocytic precursor cells. Colony-forming cells of the granulocyte-monocyte lineage (CFC-GM) did not express My-1, suggesting that the My-1 antigen is expressed later in normal granulocytic maturation. However, these antibodies did react with myeloid leukemic cell lines. The significance and potential utility of these probes for the understanding of granulopoietic differentiation is discussed.

Animals↗

PubMedDate not supplied

Two-phase [11C]L-methionine PET in childhood brain tumors.

Thirteen children (1.8-15.8 years of age) with brain tumors were studied with [11C]L-methionine positron emission tomography (METPET). Patients were injected intravenously with tracer before a baseline PET scan was obtained. To assess the sensitivity of [11C]L-methionine uptake to competitive inhibition, 10 patients received oral L-phenylalanine (100 mg/kg); 1 hour later, a second METPET was obtained. Subjective assessment of [11C]L-methionine uptake closely paralleled results of quantitative examination (r = 0.81). [11C]L-methionine uptake in tumor-containing brain was increased in 11 patients (mean ratio of [11C] radioactivity in tumor to normal brain: 1.5 +/- 0.57; range: 1.13-2.98). Increased tracer uptake occurred in ependymomas (3), medulloblastoma (1), and astrocytomas (5), but was less intense in low-grade tumors. L-phenylalanine reduced L-methionine uptake (25-69%) in 70% of studies. L-methionine uptake was not sensitive to competitive inhibition in brain radiation injury. Two-phase METPET is of potential value in difficult clinical situations evident in children with brain tumors, including the differential diagnosis of tumor recurrence and cerebral radiation injury.

Adolescent↗

PubMedDate not supplied

Paclitaxel for the treatment of progressive or recurrent childhood brain tumors: a pediatric oncology phase II study.

PURPOSE: To assess the efficacy and define the toxicity of paclitaxel given at a dosage of 350 mg/m2 every 3 weeks as a 24-hour continuous infusion to children with recurrent or progressive primary brain tumors. PATIENTS AND METHODS: Seventy-three eligible patients, ages 4 months to 19 years, with progressive or recurrent primary brain tumors were treated according to a Pediatric Oncology Group (POG) phase II protocol with paclitaxel (POG 9330). Tumor histologic strata included: astrocytoma (n = 4), malignant glioma (n = 13), medulloblastoma (n = 16), brain stem glioma (n = 15), ependymoma (n = 13), and miscellaneous histologies (n = 12). All patients had previous histologic confirmation of a primary intracranial or spinal cord tumor with magnetic resonance imaging or computed tomography documentation of unequivocally measurable progressive or recurrent disease. All patients had received previous therapy including surgery, radiation therapy, and/or chemotherapy, but no patient had been previously treated on more than one phase II trial. Paclitaxel was administered as a 24-hour intravenous infusion at a dosage of 350 mg/m2 every 3 weeks. Neurologic and neuroradiologic reevaluations were performed after every second course. Patients were allowed to continue therapy for a total of 18 cycles in the absence of progressive disease or unacceptable toxicity. RESULTS: Seventy-five patients were enrolled onto the POG 9330 protocol; two ineligible patients were removed from the study before receiving any therapy. Of the 73 eligible patients, 72 were evaluable for toxicity and 70 were either fully or partially evaluable for disease response. There was one complete response and three partial responses (5.7%). Twenty patients had stable disease for more than 2 months. Toxicities included mild nausea, central nervous system toxicity, myelosuppression, and febrile neutropenia, including one septic death. One grade 2 and two grade 3 allergic reactions occurred. No cardiac toxicities or arthralgias were reported. CONCLUSION: Paclitaxel is well tolerated in children with recurrent or progressive brain tumors at this dosage and schedule and may result in short-term disease stabilization in this patient population. The lack of a significant number of patients with measurable disease regression, however, precludes it from being identified as an active agent when administered as a single agent by 24-hour continuous infusion.

Adolescent↗