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Biomedical subjects

B Lange

Publications and source records attributed to B Lange.

At least 91 records · Page 5Linked to original sources
PubMed1992

The severe combined immunodeficient (SCID) mouse as a model for human myeloid leukemias.

Recent work has demonstrated the ability of lymphoblastic leukemias of pre-B- and T-cell origin to grow in severe combined immunodeficient (SCID) mice with a pattern reminiscent of the human clinical disease. Here, we investigated the possibility of engrafting human myeloid leukemias using both established cell lines and primary patient material. Whereas the two growth factor-independent cell lines K562 and U937 grew aggressively and induced leukemia in these animals, three other myeloid cell lines which require interleukin 3 or granulocyte-macrophage colony-stimulating factor for continuous growth in vitro failed to induce disease. Primary bone marrow and peripheral blood cells from five out of seven patients with different types of myeloid leukemias (undifferentiated, megakaryoblastic, monoblastic and chronic myelogenous leukemia in blast crisis) induced patterns of leukemic infiltration that were distinct for each leukemia subtype. The diagnosis of leukemia in SCID mice was established by microscopic detection of myeloblasts in the bone marrow, peripheral blood and, in some instances, in extramedullary sites, including the central nervous system and gonads. The karyotype and phenotype of the blasts recovered from mouse tissues were identical to those of the original patient cells. Moreover, human specific ALU sequences were amplified from the bone marrow DNA by polymerase chain reaction. Despite their ability to grow in vivo by serial transfers in SCID mice, the leukemic cells recovered from mouse tissues could not be maintained in vitro, even in the presence of recombinant cytokines. Overall, these data indicate that the SCID mouse may represent a useful animal model for human myeloid leukemias and for the development of new pharmacological and molecular approaches to therapy.

Adult↗
PubMed1991

Cloning of ALL-1, the locus involved in leukemias with the t(4;11)(q21;q23), t(9;11)(p22;q23), and t(11;19)(q23;p13) chromosome translocations.

Chromosomal region 11q23 participates in a number of reciprocal translocations with specific regions of chromosomes 4, 9, 19, and others. These translocations are associated with acute lymphocytic leukemia and acute myelomonocytic, monocytic, and myelogenous leukemia. From a yeast artificial chromosome containing human DNA derived from 11q23 we cloned a DNA fragment which can be used as a probe to detect rearrangements in leukemic cells from the majority of patients with the t(4;11), t(9;11), and t(11;19) translocations. The breakpoints cluster in a small DNA region of less than 5.8 kilobases.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1991

Chromosome 7 abnormalities in children with Down syndrome and preleukemia.

Three children, two boys and one girl, with Down syndrome (DS) who presented with preleukemia and loss of all or part of chromosome 7 were studied. Initial presentation, with cytopenias and less than 25% blasts in the bone marrow, was between 13 and 30 months of age. Progression to acute nonlymphocytic leukemia occurred 1-8 months after initial presentation. The morphologic type was megakaryoblastic in two, and undifferentiated in one. Two children achieved remission with intensive therapy, and one continues in remission off therapy; the other child died in remission of accidental causes. The third child died of respiratory distress and leukemia after no intervention was chosen. These cases represent the first examples of chromosome 7 abnormalities associated with DS and leukemia, and suggest differences from the "monosomy 7" syndrome seen in children without DS.

Child, Preschool↗
PubMed1991

Homing and progression patterns of childhood acute lymphoblastic leukemias in severe combined immunodeficiency mice.

The aim of this study was to analyze the homing and progression patterns of childhood acute lymphoblastic leukemias (ALL) in mice with severe combined immunodeficiency (SCID). Upon intraperitoneal (IP) transfer, cells from relapse samples of three children with T-lineage ALL spread hematogenously and infiltrated the non-lymphoid and/or lymphoid organs with a pattern reminiscent of the human clinical disease. These mice either died or were killed in extremis at a mean of 9 weeks. Moreover, cell lines established in vitro from two of these samples manifested identical homing and progression in the SCID mouse as compared with the original patients' cells. Thus, long-term culture of the primary leukemic T cells did not alter their invasive potential and migration pattern. When engrafted IP, three cell lines established from pre-B-ALL cases displayed primarily a lymphatic spread with induction of local tumor masses and kidney/liver nodules. Mice were killed at 11 to 13 weeks, but had not developed imminently fatal leukemia. However, when transferred intravenously, one pre-B ALL cell line was able to spread hematogenously and to infiltrate both lymphoid and non-lymphoid tissues. Overall, these data demonstrate that the SCID mouse provides an efficient and reproducible model to study the pathogenesis of childhood ALL, and may be a suitable system for evaluating therapy.

Animals↗
PubMed1991

Growth factor requirements of childhood acute T-lymphoblastic leukemia: correlation between presence of chromosomal abnormalities and ability to grow permanently in vitro.

Cells from 10 cases of childhood acute T-lymphoblastic leukemia (T-ALL) were cultured in the presence of recombinant human interleukins (rhIL) or colony-stimulating factors (CSF) to analyze their growth factor requirements and differentiative potential. Although cells from most leukemic samples displayed a short-term proliferative response to several hematopoietic growth factors, only the ones featuring chromosomal translocations could be established as permanent cell lines. Two cell lines could be initiated only in the presence of IL-3 (TALL-103 and TALL-106), one in granulocyte-macrophage CSF (GM-CSF) (TALL-101), and one in IL-2 (TALL-104); only one cell line (TALL-105) was originated in the absence of growth factors. The TALL-101 and TALL-103 cell lines, derived from very immature T-ALL cases, underwent growth factor-dependent phenotypic conversion (lymphoid to myeloid). However, the T-cell receptor rearrangement and karyotype of the original leukemic clones were retained. In contrast, the TALL-104, -105, and -106 cell lines which originated from more mature T-ALL cases, maintained a T-lymphoblastic phenotype regardless of the growth factors in which they were expanded. These data demonstrate in vitro the aggressive nature of T-ALL cases bearing chromosomal abnormalities, and indicate that the lineage commitment of the malignant clone depends on its stage of maturation in T-cell ontogeny.

Adolescent↗
PubMed1991

Comparison of search strategies for recalling double-blind trials from MEDLINE.

To minimise the effect of reference bias in literature retrieval, it is important to use computerised search strategies that give a high yield of relevant reports. In a MEDLINE search that included the Medical Subject Heading (MeSH) "Comparative study," the recall of double-blind trials of NSAIDs in rheumatoid arthritis was 93.1% (122/131) and the precision was 19.0% (122/641). When "Double-blind method" was used, either as MeSH or text words, the recall was only 72.5% (95/131) with a precision of 22.7% (95/419). A combined search strategy increased the recall to 97.7% (128/131) with a precision of 17.3% (128/738). With the MeSH term "Random allocation" only eight relevant reports were retrieved, and none was new. By using "Clinical trials" alone, we would have missed eleven reports. We conclude that "Comparative study" is preferable to "Double-blind method" when searching double-blind trials on MEDLINE.

Abstracting and Indexing↗
PubMed1991

Pulmonary metastases and bone sarcomas. Surgical removal of lesions appearing after adjuvant chemotherapy.

Pulmonary metastasis is the leading cause of death in pediatric patients with bone tumors. Multiple thoracotomies for surgical removal of individual lesions are performed at many centers. To explore the efficacy of this procedure and establish guidelines for an appropriate choice of patients, the experience with 43 thoracotomies in 24 children was reviewed. The appearance of first metastasis later than one year after diagnosis, presence of fewer than five nodules, and completeness of surgical resection were favorable predictors of postthoractomy survival. Early or multiple metastases, unresectable disease, and hilar, nodal, or pleural lesions conferred an unfavorable prognosis. With careful patient selection, pulmonary metastecotomy is a safe procedure that has few operative or long-term complications. It must be emphasized that although surgical removal of pulmonary metastases prolongs survival with good quality of life, the majority of patients with bone sarcomas ultimately succumb to their disease after thoracotomy. Follow-up time of greater than eight years is necessary to adequately assess the effectiveness of pulmonary resection in eradicating all disease in these patients.

Adolescent↗
PubMed1991

Nebraska dental professional's procedures and opinions related to infectious diseases.

Based on the findings of this study, the following specific strategic recommendations are offered: 1. Offer continuing education courses throughout the state at reasonable fees. The courses should emphasize recognition of AIDS related lesions and infectious diseases, aseptic techniques/infectious disease control, AIDS, Hepatitis B, and infections/antibiotics. In addition, continuing education courses in the area of medical history taking methods should be offered to teach methods of inquiring about sexual and drug-use histories. 2. Establish a state resource center for information regarding infectious diseases. This could, perhaps, be a cooperative venture with the Department of Health, the Nebraska Dental Association, and the College of Dentistry. There is a need to gather, interpret and disseminate periodic updates on infectious disease research. This venture should also focus on developing literature for practitioners with consistent information about infection control regulations and guidelines. 3. Either through continuing education courses or through the information resource center, provide instruction on realistic assessment of the risk of infectious disease transmission in dentistry. 4. Develop a public relations campaign to educate the public about infection control policies in dentistry, what is being done to protect the public. 5. A research effort should be undertaken to determine the discrepancy between self-reported infection control practices and observed infection control practices. This could be accomplished through patient and dentist surveys, interviews, and/or observations. 6. Establish a confidential HIV blood screening program for health care providers.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Growth factor-dependent differentiation along the myeloid and lymphoid lineages in an immature acute T lymphocytic leukemia.

Bone marrow cells from a child with an immature (CD2+, CD5+, CD7+) acute T lymphocytic leukemia (T-ALL) were cultured in the presence and absence of human rIL-2, IL-3, or granulocyte-macrophage (GM)-CSF. Cells cultured without growth factors failed to divide and those initiated in the presence of IL-2 or GM-CSF underwent maturation and terminal T lymphoid or myelomonocytic differentiation, respectively. In contrast, a permanent growth factor-dependent cell line, designated TALL-103/3, was established upon culture in IL-3. The TALL-103/3 cells gradually lost the T cell-specific markers and acquired a myeloid phenotype (CD15+, CD33+). Switching of the IL-3-dependent cells at an early passage to medium containing only human rIL-2 resulted in the establishment of a subline, named TALL-103/2, with a T lymphoid phenotype (CD3+, CD8+, TCR-gamma delta +, CD7+). The TALL-103/2 cells strictly require IL-2 for growth, are irreversibly committed to the lymphoid lineage, and cannot survive in the presence of any other hemopoietic growth factor tested so far. In contrast, the IL-3-dependent TALL-103/3 cells could be adapted to grow in synthetic (serum-free) medium also in the presence of either GM-CSF or IL-5, in which they retain a myeloid phenotype. Interestingly, after 18 mo in culture in IL-3, the TALL-103/3 cells can still be phenotypically converted to the lymphoid lineage upon addition of IL-2, thus maintaining its bipotentiality. Despite the marked phenotypic differences, the TALL-103/2 and TALL-103/3 cell lines show the same karyotypes with multiple abnormalities present in the primary malignant clone and have identical rearrangements of the TCR-gamma and -delta loci, thus confirming their derivation from a common precursor cell. Together, these findings indicate that the phenotype of immature T-ALL cells can be drastically modified by the presence of specific hemopoietic growth factors in the environment, leading to either lymphoid or myeloid lineage commitment while leaving their karyotype and genotype intact.

Antigens, CD↗
PubMed1990

Down-regulated c-myb expression inhibits DNA synthesis of T-leukemia cells in most patients.

We have investigated the functional relevance of c-myb expression for DNA synthesis in patients' T-leukemia cells. [3H]Thymidine incorporation assays of 32 patients' leukemia cells exposed in vitro to c-myb sense or antisense oligodeoxynucleotides served to define two groups of patients: a responder group whose leukemia cells showed 2- to 16-fold lower levels of [3H]thymidine incorporation in c-myb antisense-treated cultures than in c-myb sense-treated cultures (20 patients) and a nonresponder group whose cells showed comparable [3H]thymidine incorporation levels in either c-myb sense- or antisense-treated cultures (12 patients). Down-regulation of c-myb mRNA levels in cells exposed to c-myb antisense oligodeoxynucleotides was comparable in both groups of patients, indicating that differential sensitivity to c-myb antisense oligodeoxynucleotides was not due to differential uptake of these oligodeoxynucleotides. DNA polymerase alpha mRNA levels were down-regulated in cells from the responders but were unaffected in the nonresponder group. These results suggest that c-myb is required for DNA synthesis in cells of many but not all T-leukemia patients and that leukemia cells in which DNA synthesis is not inhibited despite down-regulation of c-myb expression may have undergone some genetic change(s) that obviate(s) the requirement for myb protein.

Base Sequence↗
PubMed1990

Minimal residual disease in childhood B-lineage lymphoblastic leukemia. Persistence of leukemic cells during the first 18 months of treatment.

BACKGROUND: Whether patients in clinical remission for acute lymphoblastic leukemia (ALL) continue to harbor leukemic cells is not known, because methods of detecting residual malignant cells have not been sufficiently sensitive. This information might be useful for predicting recurrence and determining the duration of therapy. METHODS: Using a sensitive new method--identifying complementarity-determining region III sequences with the polymerase chain reaction--we estimated the number of residual leukemic cells in the bone marrow of eight children with B-lineage lymphoblastic leukemia before and after remission. RESULTS: Induction chemotherapy produced a 3-to-4-log reduction in the number of leukemic cells. In all samples obtained up to 18 months after diagnosis, however, 0.004 to 2.6 percent of bone marrow nucleated cells were residual leukemic cells. Among the four patients studied more than 18 months after diagnosis, three had no detectable leukemic cells in marrow samples. Despite this, one of them, who was no longer receiving therapy, had a central nervous system relapse. In one patient receiving maintenance chemotherapy, there was a 60-fold increase in leukemic cells three months before bone marrow relapse. CONCLUSIONS: The complete disappearance of leukemic cells (or their reduction below our method's threshold of detection, 1 in 100,000 cells) may be necessary to achieve a cure of ALL. The quantification of residual leukemic cells in serial marrow aspirates during therapy may allow the early detection of relapse.

Adolescent↗
PubMed1990

Prognostic importance of serum transferrin and ferritin in childhood Hodgkin's disease.

The relationship of iron-binding proteins to prognosis was studied in 50 children at the Children's Hospital of Philadelphia, newly diagnosed with Hodgkin's disease (HD). There were five patients with Stage I, 18 with Stage II, 14 with Stage III, and 13 with Stage IV. Initial serum ferritin, transferrin, iron, hemoglobin (Hb), erythrocyte sedimentation rate (ESR), and A or B symptoms were analyzed for their association with progression-free survival (PFS). There was a linear increase of mean and median ferritin levels and a decrease of mean and median transferrin levels with advancing stages. Also, there was a significant inverse correlation between ferritin and transferrin (P less than 0.001). In univariate analyses, high ferritin (greater than 142 ng/ml) (P = 0.02) and low transferrin (less than or equal to 250 mg/dl) (P = 0.008) were significantly associated with poor PFS. Serum iron, Hb, ESR, and A or B symptoms were not associated with PFS. Stepwise proportional hazards regression analysis of all factors showed that transferrin was the only factor significantly associated with PFS. These preliminary results suggest that serum transferrin can also be used as a prognostic factor in addition to serum ferritin and that it may be helpful to assay both serum ferritin and transferrin as prognostic factors in childhood HD. Further testing of large groups of patients is needed to determine whether they are independent of tumor bulk and other established prognostic factors.

Adolescent↗
PubMed1990

Synergistic and antagonistic effects of IL-1 alpha and IL-4, respectively, on the IL-2-dependent growth of a T cell receptor-gamma delta+ human T leukemia cell line.

The TALL-103/2 cell line was derived from an immature acute T lymphocytic leukemia with T-myeloid differentiating capacity. The leukemic cells were first expanded in recombinant human IL-3 in which they acquired a myeloid phenotype, and subsequently were adapted to grow in human rIL-2 in which they became lymphoid committed. The TALL-103/2 cell line expresses only T cell-specific differentiation Ag (CD2, CD3, CD7, and CD8) but has retained the CD33 myeloid Ag originally present on the IL-3 expanded population. By using mAb directed at the TCR-alpha beta or specific for framework determinants on human TCR-gamma and -delta chains, the TALL-103/2 cells were shown to be WT31-, TCR delta 1+, TCS-1+, and Ti gamma A-, thus representing a T cell subset expressing the nondisulfide-linked form of the TCR-gamma delta. The TALL-103/2 cells have been maintained for more than 1 y in the presence of human rIL-2 on which they are strictly dependent. Chemical cross-linking and immunofluorescence studies indicate the presence of both high and intermediate affinity IL-2R on the TALL-103/2 cells. Whereas mAb antiTac and H-31 with reactivity to the IL-2R alpha-chain (p55) compete only partially for the IL-2-induced proliferation of these cells, mAb TU27, specific to the IL-2R beta-subunit (p75), inhibits such growth completely even at high concentrations of IL-2. The interactions of the two T cell-stimulating factors IL-1 and IL-4 on the IL-2-dependent growth of TALL-103/2 cells were investigated. IL-1 alpha synergizes with IL-2 in supporting the short and long term growth of this cell line, whereas IL-4 abrogates its growth. These effects are, at least in part, due to the modulation of IL-2R expression induced by the two lymphokines. Functionally, the TALL-103/2 cells display MHC-nonrestricted cytotoxic activity that is significantly enhanced by addition of either IL-4, IL-6, or IFN-gamma. Because of its properties and its stable requirement for IL-2 for continuous growth, this T lymphocytic leukemia-derived cell line represents an interesting model to analyze ontogeny and function of leukemic T cells.

Antigens, CD↗
PubMed1990

Molecular anatomy of a 5q interstitial deletion.

A truncated granulocyte-macrophage colony-stimulating factor (GM-CSF) allele on a putative 5q- chromosome of HL-60 cells was cloned and, by comparison with counterpart normal sequences, analyzed for clues to molecular mechanisms facilitating rearrangement and deletion. Within the 17-kilobase (kb) pair locus surrounding the truncated GM-CSF gene remnant, there are no fewer than four rearranged genomic fragments that seemingly derive from chromosome 5 region q21----23. Two of the fragments, which flank the truncated GM-CSF locus on the 5q-, are contiguous on the normal chromosome 5, centrometric to the normal GM-CSF allele, indicating at least one intrachromosomal insertion event, either preceded or followed by further deletion. Insertion and/or deletion was accompanied by juxtaposition of LINE sequences to the 5' side of the truncated GM-CSF locus within the inserted fragment. The entire rearranged locus is embedded in repetitive sequences, which may have mediated successive insertions or deletions. The extent of such stepwise deletions, resulting in loss of genes such as interleukin-3 (IL-3), IL-4, IL-5, and GM-CSF, whose gene products are critical to differentiation within the lineage of the affected hematopoietic stem cell, may be mirrored in the heterogeneity of symptoms and 5q- deletion sizes observed in myelodysplasias and acute leukemias carrying a 5q- chromosome. Perhaps most significantly, the sequences surrounding the insertion/deletion region are suggestive of recombination signals, including direct repeats and mirrored repeats. The site of insertion of the GM-CSF 3' region into an upstream (centromeric) locus is flanked by direct repeats; the upstream site into which it is inserted is also flanked by 12 base pair (bp) direct repeats. After insertion, one member of each pair of repeats is lost. The organization of this rearranged locus implies that direct repeats had a role in the intrachromosomal recombination/deletion event.

Base Sequence↗
PubMed1990

Bone marrow transplantation for childhood Ki-1 lymphoma.

Two children with Ki-1 antigen-positive, non-Hodgkin's lymphoma received high-dose chemotherapy, fractionated total body irradiation (TBI), and allogeneic bone marrow transplantation. Both patients had relapsed multiple times on conventional chemotherapy and radiation therapy. Following transplantation, there was successful engraftment with disappearance of clinical signs and symptoms of their disease. As of June 1, 1989 they are in continuous unmaintained complete remission, 56 and 40 months, respectively, after bone marrow transplantation.

Adolescent↗
PubMed1990

Immunization of children with acute lymphoblastic leukemia with live attenuated varicella vaccine without complete suspension of chemotherapy.

A total of 44 children with acute lymphoblastic leukemia were immunized against chickenpox with the Oka/Merck strain live attenuated varicella vaccine. Of these children, 24 continued oral chemotherapy with 6-mercaptopurine during the immunization period and 20 had suspension of all chemotherapy for 1 week before and 1 week after the vaccine. Seroconversion, as determined by the detection of fluorescent antibody to membrane antigens, occurred in 91% and did not differ between patients continuing 6-mercaptopurine from those in whom chemotherapy was suspended. Fever and/or rash occurred in less than one third of vaccinated children. Unexpected reactions occurred in two vaccinated children, one from each group, both of whom had low absolute lymphocyte counts (less than 750/microL) on the day of immunization. Vaccine-induced immunity appeared effective in preventing or modifying chickenpox after exposure to natural disease.

Adolescent↗