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Biomedical subjects

L D Cooley

Publications and source records attributed to L D Cooley.

At least 19 recordsLinked to original sources
PubMed2005

Inversion of two-band superconductivity at the critical electron doping of (Mg, Al)B2.

Electron energy-loss spectroscopy (EELS) was combined with heat capacity measurements to probe changes of electronic structure and superconductivity in Mg(1-x)Al(x)B(2). A simultaneous decrease of EELS intensity from sigma-band hole states and the magnitude of the sigma gap was observed with increasing x, thus verifying that band filling results in the loss of strong superconductivity. These quantities extrapolated to zero at x approximately 0.33 as inferred from the unit cell volume. However, superconductivity was not quenched completely, but persisted with T(c) < 7 K up to about x approximately 55. Only the pi band had detectable density of states for 0.33 < or =x < or = 0.55, implying an inversion of the two-band hierarchy of MgB(2) in that regime. Since pi-band superconductivity is active in other materials such as intercalated graphite, implications for new materials with high T(c) are discussed.

Journal Article↗
PubMed2005

Accumulation of methotrexate and methotrexate polyglutamates in lymphoblasts and treatment outcome in children with B-progenitor-cell acute lymphoblastic leukemia: a Pediatric Oncology Group study.

We reported that children with B-progenitor-cell acute lymphoblastic leukemia (BpALL) treated in the early 1980s whose lymphoblasts accumulated high levels of methotrexate (MTX) and of methotrexate polyglutamates (MTXPGs) in vitro had an improved 5-year event-free survival (EFS) (65% (standard error (s.e.) 12%) vs 22% (s.e. 9%)). We repeated this study in children with BpALL treated in the early 1990s. The major change in treatment was the addition of 12 24-h infusions of 1 g/M2 MTX with leucovorin rescue (IDMTX). In 87 children treated on Pediatric Oncology Group (POG) study 9005 and POG 9006, the 5-year EFS for those whose lymphoblasts accumulated high levels of MTX and MTXPGs (79.2%, s.e. 8.3%) was not significantly different from that of patients with lesser accumulation of MTX and MTXPGs (77.7%, s.e. 5.4%). These findings support the notion that higher dose MTX therapy has contributed to increased cure, particularly for patients whose lymphoblasts accumulate the drug less well.

Antimetabolites, Antineoplastic↗
PubMed2001

High critical current density and enhanced irreversibility field in superconducting MgB2 thin films.

The discovery of superconductivity at 39 K in magnesium diboride offers the possibility of a new class of low-cost, high-performance superconducting materials for magnets and electronic applications. This compound has twice the transition temperature of Nb3Sn and four times that of Nb-Ti alloy, and the vital prerequisite of strongly linked current flow has already been demonstrated. One possible drawback, however, is that the magnetic field at which superconductivity is destroyed is modest. Furthermore, the field which limits the range of practical applications-the irreversibility field H*(T)-is approximately 7 T at liquid helium temperature (4.2 K), significantly lower than about 10 T for Nb-Ti (ref. 6) and approximately 20 T for Nb3Sn (ref. 7). Here we show that MgB2 thin films that are alloyed with oxygen can exhibit a much steeper temperature dependence of H*(T) than is observed in bulk materials, yielding an H* value at 4.2 K greater than 14 T. In addition, very high critical current densities at 4.2 K are achieved: 1 MA cm-2 at 1 T and 105 A cm-2 at 10 T. These results demonstrate that MgB2 has potential for high-field superconducting applications.

Journal Article↗
PubMed2001

Strongly linked current flow in polycrystalline forms of the superconductor MgB2.

The discovery of superconductivity at 39 K in magnesium diboride, MgB2, raises many issues, a critical one being whether this material resembles a high-temperature copper oxide superconductor or a low-temperature metallic superconductor in terms of its behaviour in strong magnetic fields. Although the copper oxides exhibit very high transition temperatures, their in-field performance is compromized by their large anisotropy, the result of which is to restrict high bulk current densities to a region much less than the full magnetic-field-temperature (H-T) space over which superconductivity is found. Moreover, the weak coupling across grain boundaries makes transport current densities in untextured polycrystalline samples low and strongly sensitive to magnetic field. Here we report that, despite the multiphase, untextured, microscale, subdivided nature of our MgB2 samples, supercurrents flow throughout the material without exhibiting strong sensitivity to weak magnetic fields. Our combined magnetization, magneto-optical, microscopy and X-ray investigations show that the supercurrent density is mostly determined by flux pinning, rather than by the grain boundary connectivity. Our results therefore suggest that this new superconductor class is not compromized by weak-link problems, a conclusion of significance for practical applications if higher temperature analogues of this compound can be discovered.

Journal Article↗
PubMed2000

Donor cell leukemia: report of a case occurring 11 years after allogeneic bone marrow transplantation and review of the literature.

We report the case of a man with chronic myelocytic leukemia (CML) and a 46,XY,t(5;9;22) karyotype who developed acute myelocytic leukemia (AML) with a 45,X,t(8;21) karyotype 11 years after bone marrow transplantation (BMT) from his HLA-matched sister. Fluorescent in situ hybridization (FISH) studies and molecular analysis using short tandem repeat (STR) sequences proved the new leukemia to be of donor cell origin. Donor cell leukemia (DCL) after BMT is rare. Our review of the literature found 15 cases following BMT for leukemia and 2 cases after BMT for benign hematological disorders. In fewer than half the reported cases were molecular studies available to confirm the cytogenetic evidence for DCL, and the longest previously reported interval between BMT and DCL was 6 years.

Adult↗
PubMed2000

Immunohistochemical determination of HER-2/neu expression in invasive breast carcinoma.

Numerous methods exist for HER-2/neu assessment; however, technical and interpretive standardization is virtually absent. We evaluated 2 commercially available antibodies on routinely fixed paraffin-embedded tissue sections to establish our own guidelines. Thirty-three cases of infiltrating breast carcinoma were evaluated simultaneously with monoclonal and polyclonal antibodies. Only membranous staining, no matter how focal, was considered positive. An additional 32 tumors were studied subsequently using only the polyclonal antibody. Of all carcinomas, 13.0% showed immunohistochemical evidence of HER-2/neu overexpression. High-grade tumors were more often positive. There was no HER-2/neu gene expression in the benign epithelium that generally was present in the tissue section or in any of the well-differentiated tumors tested. The polyclonal antibody proved more sensitive than the monoclonal antibody. While true cytoplasmic staining was present occasionally, it did not create substantial difficulty in interpretation. The polyclonal antibody cost substantially less than the monoclonal antibody. Fluorescence in situ hybridization assay for HER-2/neu gene amplification performed on 32 of 65 cases showed concordant results in 31 cases. The immunohistochemical assay for HER-2/neu gene overexpression, using our methods, is accurate, economic, and easily integrated into the laboratory.

Antibodies↗
PubMed2000

Malignant peripheral nerve sheath tumor with a t(X;18).

We describe an ankle tumor arising in a 16-year-old girl. The tumor demonstrated histology typical of a malignant peripheral nerve sheath tumor (MPNST), but exhibited a variant form of the (X;18) translocation associated with synovial sarcoma. Immunohistochemical stains were positive for vimentin, CD57, collagen type IV, and Bcl-2. Routine and molecular cytogenetic studies showed an unbalanced 3-way chromosomal translocation that involved chromosomes X, 18, and 1. Electron microscopic findings were noncontributory. This unusual tumor raises the following questions and possibilities: (1) As the t(X;18) suggests, could this tumor be a monophasic synovial sarcoma with the histologic features of an MPNST? (2) Or, as the histology suggests, is this tumor an MPNST that has a t(X;18)? (3) Finally, could MPNST histology, a t(X;18), and no defining immunohistochemical or electron microscopic features represent an as yet unrecognized part of a spectrum that spans from synovial sarcoma to MPNST or other spindle cell tumors?

Adolescent↗
PubMed1999

Extensive analysis of mosaicism in a case of Turner syndrome: the experience of 287 cytogenetic laboratories. College of American Pathologists/American College of Medical Genetics Cytogenetics Resource Committee.

OBJECTIVE: To assemble and interpret karyotype data provided as part of the College of American Pathologists/American College of Medical Genetics Cytogenetics Proficiency Testing Program. DATA SOURCES, EXTRACTION, AND SYNTHESIS: The Cytogenetics Resource Committee requested data on all cells analyzed in a 1994 whole-blood specimen challenge. In that study, 287 participating laboratories analyzed a total of 14297 cells derived from a sample drawn from an adult donor with Turner syndrome. This individual had previously been found to have mosaicism, including cell lines with X structural anomalies along with monosomy X, making this an excellent challenge for a multicenter cytogenetic survey. RESULTS AND CONCLUSIONS: Analysis of the data from this extensive study revealed mosaicism of up to 10 different sex chromosome complements involving the X chromosome with and without a small ring X or a derivative X chromosome. In the routine cytogenetic analysis performed by the participating laboratories, cell lines observed, in decreasing order of prevalence, included 45,X (n = 8357 cells), 46,X,r(X) (n = 3597), 46,X,der(X)t(X;X) (n = 2237), 46,XX (n = 93), 47,X,r(X),r(X) (n = 5), 47,X,der (X)t(X;X),der(X)t(X;X) (n = 3), 47,XX,r(X) (n = 2), and one observation each of 47,XX,der(X)t(X;X), 47,X,der(X)t (X;X),r(X), and 47,XXX. Our molecular cytogenetic data, as well as detailed analysis of G-banded chromosomes, suggest the nomenclature for these 2 abnormal X chromosomes as r(X)(p11.3q21.3) and der(X)t(X;X)(p11.3;q21.3), and we discuss models for the concomitant formation of these 2 entities. Both the degree of analysis and the extensive mosaicism that was discovered in this study are exceptional, and similar reported cases as well as possible mechanisms for the observed X chromosome instability are reviewed.

Adult↗
PubMed1998

Cytogenetic analysis of a scapular chondromyxoid fibroma.

Chondromyxoid fibroma (CMF) is a rare cartilaginous tumor of bone. It typically presents in the lower extremities of young males. Cytogenetic analysis of two chondromyxoid fibromas has been previously reported. We studied a scapular CMF from an 11-year-old female by cytogenetic and molecular cytogenetic methods and found an unbalanced reciprocal translocation between the short arm of chromosome 3 and the long arm of chromosome 6. In this translocation, several bands from chromosome 3 (3p12, 3p13, 3p14, 3p21) are lost and several bands on chromosome 6 (6q21, 6q22, 6q23) appear rearranged. Two known cartilage-related genes are located in the regions affected by this unbalanced rearrangement: the type X collagen gene (COL10A1) located at 6q21-q22 and the parathyroid hormone/parathyroid hormone-related peptide receptor gene (PTH/PTHrP) located at 3p21.1-p22. These genes function to control growth and maturation of endochondral bone, the site of origin of cartilaginous tumors.

Bone Neoplasms↗
PubMed1998

Detection of double minute chromosomes in a child with acute lymphoblastic leukemia.

A child with acute lymphoblastic leukemia (ALL) whose predominant leukemic clone demonstrated double minute chromosomes (dmin) is presented. The patient had no history of mutagen or carcinogen exposure and responded well to combination chemotherapy. Although dmin have been described in acute myelogenous leukemia and various solid tumors in adults, their presence in childhood neoplasms is less frequent and limited primarily to neurogenic tumors. This is the first documentation of dmin in childhood ALL, suggesting that there may be an unrecognized subgroup of ALL patients with gene amplification.

Child↗
PubMed1998

Accumulation of methotrexate polyglutamates, ploidy and trisomies of both chromosomes 4 and 10 in lymphoblasts from children with B-progenitor cell acute lymphoblastic leukemia: a Pediatric Oncology Group Study.

Levels of accumulation of methotrexate polyglutamates were measured in vitro in lymphoblasts obtained at diagnosis from children with B-progenitor cell acute lymphoblastic leukemia (pro-B ALL). They were compared to numerical and structural chromosomal abnormalities present in these leukemic cells. In a series of 95 patients, the percent with high lymphoblast methotrexate polyglutamate levels increased with the increase in modal number of total chromosomes (p<0.001). Thus, lymphoblast methotrexate polyglutamate accumulation appeared to be closely linked to the extent of hyperdiploidy in childhood pro-B ALL. Lymphoblasts from 35 (88%) of the 40 children with hyperdiploid (>50 chromosomes) and 23 (88%) of 26 with hyperdiploid (DNA Index >1.16) pro-B ALL accumulated high levels of methotrexate polyglutamate, suggesting that they were more sensitive to methotrexate cytotoxicity. While children with hyperdiploid (DNA Index >1.16) pro-B ALL have a good prognosis, those with trisomies of both chromosomes 4 and 10, almost all of whom are hyperdiploid, have an even better outcome. There was no significant difference in methotrexate polyglutamate levels in lymphoblasts from 19 children with and 21 without trisomies of both chromosomes 4 and 10 (p = 0.25). The improved response to multi-agent chemotherapy conferred by the presence of trisomies of both chromosomes 4 and 10 in such patients may be due to increased sensitivity of their lymphoblasts to one or more anti-leukemic agents in addition to methotrexate.

Adolescent↗
PubMed1997

The first recurring chromosome translocation in hepatoblastoma: der(4)t(1;4)(q12;q34).

We report four cases of hepatoblastoma with a derivative chromosome 4 from an unbalanced translocation between the long arms of chromosomes 1 and 4, an aberration reported only rarely in isolated cases of other types of neoplasms. The abnormality in three hepatoblastomas was der(4)t(1;4)(q12;q34), whereas the fourth case appeared to have a der(4)t(q25;q32). All had hyperdiploid tumor karyotypes; however, in the case with t(q25;q32), the der(4) was the only abnormality in the stemline. We speculate that the oncogenetic event in our cases may be the loss of a gene on distal 4q or their alteration by juxtaposition to 1q12 heterochromatin.

Chromosome Banding↗
PubMed1997

Cytogenetic analysis of 120 primary pediatric brain tumors and literature review.

We report chromosome results from 108 pediatric central nervous system (CNS) tumors. From our data and those in the literature we found that (1) cerebellar and low-grade astrocytic tumors, including gangliogliomas, are most often karyotypically normal; (2) supratentorial tumors were more frequently high-grade tumors that demonstrated a complex karyotype. Chromosome abnormalities were similar to those described in adult astrocytic tumors, namely, +7, 9p abnormalities, and -10; (3) primitive neuroectodermal tumors (PNETs) were virtually always karyotypically abnormal with a high frequency of +7, -8, i(17q), and -22. PNETs with -22 may represent a subset of tumors; (4) typical choroid plexus papillomas showed a normal karyotype, atypical papillomas showed a hyperdiploid karyotype (with +7, +12, and +20), choroid plexus carcinomas showed a hyperhaploid karyotype; (5) a few ependymomas showed hyperdiploidy or hypertetraploidy; (6) germ cell tumors showed complicated karyotypes; (7) monosomy 22 or 22q abnormalities appear to be a recurring finding in the malignant rhabdoid tumors; and (8) meningiomas showed -22 or 22q abnormalities associated with a complex karyotype. In general, in pediatric CNS tumors the least differentiated neoplasms have the greatest number of cytogenetic abnormalities. However, our present morphologic criteria for tumor diagnosis do not always correlate with a consistent karyotype, and further study of pediatric brain tumor morphology, site, behavior, and karyotype is required.

Astrocytoma↗
PubMed1997

Pilot studies for proficiency testing using fluorescence in situ hybridization with chromosome-specific DNA probes: a College of American Pathologists/American College of Medical Genetics Program.

Fluorescence in situ hybridization using chromosome-specific DNA probes is rapidly becoming part of clinical laboratory practice for certain congenital and neoplastic disorders. Current legislation requires proficiency testing for clinical laboratory studies. To evaluate the efficacy of fluorescence in situ hybridization proficiency testing, we invited 19 representative institutions to participate in three pilot studies. One study used probes for the X and Y chromosomes to evaluate metaphase spreads and interphase nuclei. Another study used probes for bcr and abl to detect bcr/abl fusion in interphase nuclei in chronic myelogenous leukemia. The third study used a D22S75 probe to detect microdeletions in metaphase spreads from a patient with velocardiofacial syndrome. The results of these studies demonstrate that proficiency testing with fluorescence in situ hybridization is attainable using either metaphase or interphase preparations, and that either microscope slides or fixed cell pellets are suitable.

Chromosome Mapping↗
PubMed1996

Infant cardiac fibroma with clonal t(1;9)(q32;q22) and review of benign fibrous tissue cytogenetics.

Cardiac fibromas are rare lesions which occur more frequently in infants and children than in the adult population. These tumors are nonmalignant proliferations of connective tissue most often found in the left ventricular myocardium or septal myocardium. No cytogenetic studies of cardiac fibromas have been reported. We report a case of an infant with a subepicardial tumor in whom the cytogenetic analysis showed a clonal reciprocal translocation, 46,XY,t(1;9)(q32;q22),inv(9)(p11q12)c. We review the literature regarding cardiac fibromas and briefly discuss the cytogenetics of benign fibrous neoplasias.

Chromosomes, Human, Pair 1↗
PubMed1996

Pancytopenia with chromosomal fragility: vitamin B12 deficiency.

PURPOSE: Pancytopenia in children may have many etiologies. Chromosomal abnormalities with pancytopenia is of particular concern because clonal abnormalities indicate a neoplastic process. We describe three children who had vitamin B12 deficiency and who displayed pancytopenia with multiple chromosomal breaks, rearrangements, and deletions consistent with chromosomal fragility. Severe vitamin B12 deficiency is rare in children and should be considered in the differential diagnosis of a child with pancytopenia, dyserythropoiesis, and multiple chromosomal abnormalities. PATIENTS AND METHODS: Three children displayed pancytopenia with dyserythropoiesis in the bone marrow. Routine cytogenetic analyses in all three patients were performed and chromosome breakage study was performed on the peripheral blood of one patient after vitamin B12 supplementation. RESULTS: All three patients had severe vitamin B12 deficiency. Spontaneous chromosomal fragility was seen in routine cytogenetic analyses in all three patients. Vitamin B12 supplementation resolved the pancytopenia in all three patients and spontaneous and diepoxybutane-induced breakage rates in chromosomes were well within normal rates after therapy in one patient. CONCLUSION: The presence of pancytopenia with cytogenetic abnormalities in a child is worrisome. However, careful interpretation of dyserythropoiesis and megaloblastic changes in bone marrow in the aforementioned clinical situation would result in the correct diagnosis of a disorder that is easily cured.

Bone Marrow↗