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Biomedical subjects

C A Hanson

Publications and source records attributed to C A Hanson.

At least 91 records · Page 5Linked to original sources
PubMed1990

Identification of two related markers for common acute lymphoblastic leukemia as heat shock proteins.

By direct analysis of the polypeptide constituents of leukemic cells, we have previously detected several polypeptides that are restricted in their expression to acute lymphoblastic leukemia (ALL). In this study, we provide evidence that two polypeptides designated L2 and L4 are structurally related and represent novel markers for common ALL. Partial amino acid sequence analysis did not uncover differences between L2 and L4. The sequences obtained correspond to a previously cloned human gene designated hsp 27 that is expressed, following heat shock treatment, in a variety of cells. 32Pi incorporation studies indicate that L4 is an unphosphorylated form and L2 is a phosphorylated form of hsp27. The two forms were inducible by heat shock in leukemic and nonleukemic lymphoid cells. Thus, in acute leukemia, the common ALL subtype is uniquely characterized by the constitutive expression of a polypeptide that represents a major cellular phosphoprotein.

Amino Acid Sequence↗
PubMed1990

Theory and applications of the polymerase chain reaction.

The polymerase chain reaction (PCR) is a newly developed molecular biology technique that can significantly amplify DNA or RNA. The process consists of repetitive cycles of specific DNA synthesis, defined by short stretches of preselected DNA. With each cycle, there is a doubling of the final, desired DNA product such that a million-fold amplification is possible. This powerful method has numerous applications in diagnostic pathology, especially in the fields of microbiology, forensic science, and hematology. The PCR may be used to directly detect viral DNA, which may facilitate the diagnosis of acquired immune deficiency syndrome (AIDS) or other viral diseases. PCR amplification of DNA allows detection of specific sequences from extremely small samples, such as with forensic material. In hematology, PCR may help in the diagnosis of hemoglobinopathies or of neoplastic disorders by documenting chromosomal translocations. The new PCR opens exciting new avenues for diagnostic pathology using this new technology.

DNA↗
PubMed1990

Detection of Philadelphia chromosome-positive cells from glass slide smears using the polymerase chain reaction.

Southern and Northern blot hybridization studies and the polymerase chain reaction (PCR) have been used to analyze the bcr-abl gene complex in chronic myelogenous leukemia (CML). Because fresh or cryopreserved cells may not always be available for molecular analyses, we investigated the possibility of using routinely prepared glass slide smears of blood or bone marrow as our source of cellular material. Cellular RNA was prepared directly from the blood or bone marrow smears using a modified RNA extraction procedure. cDNA was synthesized from RNA and amplified with PCR using bcr and abl-specific primers. Using this procedure, the bcr-abl fusion gene was detected by PCR in 21 of 21 patients with CML. Three patients who had undergone allogenic bone marrow transplantation (BMT) for CML were also studied by PCR. bcr-abl was identified transiently in one patient, persisted in one patient after BMT for 2 years until relapse occurred, and was absent in one patient to 18 months after BMT. We have shown that PCR can detect the bcr-abl gene of CML using material from glass-slide smears. This technique may be useful as a general approach in evaluating archival hematologic specimens for the expression of critical gene products.

Bone Marrow Transplantation↗
PubMed1989

Human T-cell lymphotropic virus type I (HTLV-I)-associated adult T-cell leukemia-lymphoma in a patient infected with human immunodeficiency virus type 1 (HIV-1).

A patient had adult T-cell leukemia-lymphoma in the unusual setting of coinfection with human immunodeficiency virus type 1 (HIV-1) and human T-cell lymphotropic virus type I (HTLV-I). The leukemic cells were CD4 positive and showed clonal genetic rearrangement of the T-cell receptor complex. Cytogenetic analysis showed three clonal karyotypic abnormalities: trisomy 3 and two translocations [t(1;15), (X;1)]. The patient was seropositive for HIV and HTLV-I; HTLV-I and HIV-1 DNA sequences were detected in peripheral blood leukocytes by the polymerase chain reaction. The HTLV-I sequences were detected in a relatively high proportion of mononuclear cells (at least 1 in 30 cells), whereas HIV-1 sequences were detected in a smaller proportion of cells (at least 1 in 3000 cells). Clinical remission was achieved after chemotherapy. There was a decrease in the proportion of HTLV-I positive mononuclear cells (at least 1 in 1000 cells), whereas the proportion of HIV-1 positive cells was relatively unchanged (at least 1 in 1000 cells). Adult T-cell leukemia-lymphoma in the setting of HIV coinfection may become increasingly common because asymptomatic retroviral coinfections are frequent.

Adult↗
PubMed1989

Markedly diminished epidermal keratinocyte expression of intercellular adhesion molecule-1 (ICAM-1) in Sézary syndrome.

In mycosis fungoides the malignant T cells express lymphocyte function-associated antigen-1, which allows them to bind to epidermal keratinocytes expressing the gamma interferon-inducible intercellular adhesion molecule-1. In this report, a patient with leukemic-stage mycosis fungoides (Sézary syndrome) had widespread erythematous dermal infiltrates containing malignant T cells, but without any epidermotropism. We discovered that the T cells expressed normal amounts of functional lymphocyte function-associated antigen-1, but the keratinocytes did not express significant levels of intercellular adhesion molecule-1, which was probably due to the inability of the malignant T cells to produce gamma interferon. These results support the concept that the inability of malignant T cells to enter the epidermis may contribute to emergence of more clinically aggressive T-cell clones that are no longer confined to the skin, but infiltrate the blood, lymph nodes, and viscera, as is seen in Sézary syndrome.

Aged↗
PubMed1989

Primary lymph node presentation of angiocentric lymphoma associated with features of a hemophagocytic syndrome.

The spectrum of post-thymic T-cell neoplasia includes the angiocentric immunoproliferative lesions, a group of disorders histologically exhibiting vascular infiltration and destruction; included among these disorders is angiocentric lymphoma. In contrast to the typical extranodal presentation seen in the angiocentric immunoproliferative lesions, this report describes a case of angiocentric lymphoma presenting as primary lymph node disease with clinicopathologic findings mimicking a hemophagocytic syndrome. Rearrangement of the T-cell receptor beta chain documents this case to be a clonal T-cell neoplasm. The association of this distinct histologic type of T-cell malignancy with hemophagocytic syndromes is reviewed.

Adult↗
PubMed1989

Flow cytometric analysis of cytologic specimens in hematologic disease.

Cytologic evaluation of body fluids and fine needle aspirations (FNA) is frequently required in patients with hematologic diseases. In this study we have correlated immunophenotyping and DNA analysis by flow cytometry with cytologic findings and tissue biopsies from 20 patients with body fluid specimens and 5 with FNA. Nineteen of 25 cases, including all FNA cases, had an immunophenotype consistent with malignancy: 12 monoclonal B-cell lymphomas, 2 T-cell lymphomas, 2 T-ALL and 3 non-T-ALL. By cytologic examination, 14 of these 19 cases were positive for malignant cells, 2 suspicious and 3 negative; the latter 5 cases, including 2 FNA cases, had small monoclonal B-cell populations detected by flow cytometry. Six cases had a benign immunophenotype; cytologic examination was benign in 4 of these and suspicious for lymphoma in 2. Our results show the feasibility of using flow cytometry to evaluate body fluids or FNA and demonstrate that small malignant populations that may be missed by routine cytology can be detected by flow cytometry.

Biopsy, Needle↗
PubMed1989

A multilobular variant of hairy cell leukemia with morphologic similarities to T-cell lymphoma.

Hairy cell leukemia is a distinct chronic lymphoproliferative disorder composed of morphologically unique B-lymphocytes. The diagnosis of hairy cell leukemia is usually based on the morphology of blood/bone marrow aspirate smears and bone marrow sections. We report three cases of hairy cell leukemia that had an unusual multilobated nuclear appearance seen on both smears and tissue sections. Many of the hairy cells exhibited marked nuclear lobulations and convolutions, giving rise to clover leaf-like nuclear configurations. The nuclear chromatin was finely reticular and characteristic of hairy cell leukemia. Bone marrow sections were hypercellular and the leukemic infiltrate was loosely distributed. A leukemic infiltrate was also seen in splenic sections in two cases in which splenectomy was carried out. Tartrate-resistant acid phosphatase cytochemistry was positive in all three cases. Flow cytometric analysis and paraffin section immunoperoxidase studies confirmed the B-cell lineage of the leukemic cells in all cases. The multilobulated nuclei described in these three cases are quite unusual in hairy cell leukemia; they could potentially lead to an erroneous diagnosis of T-cell lymphoma or leukemia. Features typical of hairy cell leukemia, such as the nuclear chromatin distribution and pattern of bone marrow infiltration, together with the clinical history, are helpful in establishing a correct diagnosis of these variant cases of hairy cell leukemia.

Adult↗
PubMed1989

True histiocytic lymphoma: histopathologic, immunophenotypic and genotypic analysis.

Five cases of true histiocytic lymphoma (THL) were analysed by immunophenotyping and immunoglobulin/T-cell receptor genotyping. These cases showed striking morphologic diversity but a strong degree of immunophenotypic homogeneity. The malignant cells reacted with multiple histiocytic markers including CD11c (Ki-M1, LeuM5), CD14, CD68 (Ki-M6) and Ki-M8; anti-HLA-DR and non-specific esterase staining was also found in all cases. The malignant cells did not express monoclonal immunoglobulin and did not react with the B- or T-cell monoclonal antibodies used except for those known to be cytoplasmically expressed in monocytes/histiocytes, such as CD4 and CD19; B- and T-cell staining was otherwise limited to background small lymphocytes. By genotypic analysis, three cases showed rearrangements: one with T beta, one with T beta and immunoglobulin heavy chain (JH) and one with both JH and light chain; the remaining two cases retained their immunoglobulin and T-cell receptor genes in germline configuration. The results not only suggest that certain subsets of the histiocyte/reticulum cell system may be capable of rearranging immunoglobulin or T beta genes while simultaneously expressing multiple histiocytic surface antigens but also demonstrate the necessity of using multiple histiocytic-specific monoclonal antibodies and cytochemical staining in diagnosing THL. Gene rearrangement studies must be interpreted in conjunction with immunophenotyping and morphology in the determination of cell lineage.

Adolescent↗
PubMed1989

Association of a mature B cell leukemia with a 4p+ chromosomal abnormality: derivation and characterization of a cell line.

We have found a single 4p+ chromosomal abnormality, 46,XX, -4, +der(4)t(3;4)(q13.3;p16), in a patient with an unusual B cell leukemia of mature phenotype characterized by a high white cell count, tartrate-resistant acid phosphatase-positive malignant cells, splenic white pulp proliferation, and a serum IgM monoclonal gammopathy. The malignant cells were characterized by surface expression of CD19 (B4), CD20 (B1), IgM, IgD, kappa, and HLA-DR. They were weakly positive for CD21 (B2) and negative for CD25 (interleukin-2 receptor). The malignant cells also showed clonal rearrangement of the immunoglobulin heavy chain and kappa light chain genes. A cell line, designated HCLW-3B, was derived from unstimulated peripheral blood obtained during the leukemic phase and was found to contain the same 4p+ chromosomal abnormality as well as genomic sequences of the Epstein-Barr virus nuclear antigen. A somatic cell hybrid constructed from HCLW-3B containing the derivative chromosome 4 was used to confirm that chromosome 3q was the source of the translocated material. The availability of a cell line which is clonally derived from the patient's circulating leukemia cells should permit further characterization of this translocation at the molecular level.

Blotting, Southern↗
PubMed1989

Epstein-Barr-virus-related post-bone-marrow-transplant lymphoproliferative disease: association with cytomegalovirus infection and Down syndrome donor marrow.

We describe the development of Epstein-Barr-virus (EBV)-related lymphoproliferative disease (LPD) in the recipient of a histocompatible bone marrow transplant (BMT). Although this rare complication is more common in recipients of mismatched bone marrow, several distinguishing features of our case may have contributed to the development of LPD in the recipient of a matched bone marrow transplant. The patient had received marrow from a sibling with Trisomy 21, a syndrome associated with variable cellular and humoral immune defects. Our patient also was infected with cytomegalovirus and was treated with immunosuppressant therapy for graft versus host disease. Although development of LPD in transplant recipients is a multifactorial process, either acquired or congenital immunosuppression/dysregulation is a common prerequisite for the process. Our case suggests that subtle immune defects in individuals with Down syndrome may contribute to the immunosuppressed setting in which EBV-related LPD can develop.

Adolescent↗
PubMed1989

Applications of flow cytometry in diagnostic pathology.

The growth of flow cytometry in diagnostic pathology has been aided by the development of instruments that can be incorporated into the pathology laboratory and new assays that have expanded the role of flow cytometry in clinical medicine. The evaluation of DNA content in solid tumors is rapidly becoming a routine procedure in surgical pathology; this topic is only briefly covered here and has been more completely reviewed elsewhere. Other assays are more completely discussed, including reticulocyte analysis, identification of antiplatelet and antineutrophil antibodies in immune cytopenias, and lymphocyte antibodies in organ transplant cross-matching. Mitogen cell cycle analysis, detection of nuclear antigens, and neutrophil function assays are also briefly covered. This review is intended to increase the awareness of how flow cytometry can be incorporated into the clinical pathology laboratory, beyond its traditional use in monoclonal antibody immunophenotyping.

Antibodies↗
PubMed1989

Tuberculosis skin testing and preventive therapy.

Tuberculin skin testing is a reliable tool for the detection of tuberculous infection and the eventual prevention of tuberculous disease. False-negative tests may occur in individuals with a compromised immune system, including those with human immunodeficiency virus (HIV) infection, persons taking immunosuppressive drugs (eg. corticosteroids), the severely malnourished, and the elderly. Nevertheless, it still is useful in detecting infection in those persons who are in close contact with patients with tuberculous disease, including family members, hospital personnel, and those from high risk areas. Once a skin test is found to be reactive, further diagnostic studies should be done to rule out tuberculous disease. Once ruled out, preventive therapy with isoniazid should be instituted. Suitable candidates for prophylaxis include all individuals with reactive tuberculin skin tests who are (1) household contacts of patients with tuberculous disease, (2) recent tuberculin test convertors, (3) individuals with prior tuberculosis (TB) who did not receive adequate chemotherapy, (4) all individuals under the age of 35, and (5) individuals in special clinical circumstances who are over the age of 35. Newer, shorter course regimens are currently being studied. TB cannot be eliminated until the importance of preventive therapy is recognized by all.

Humans↗
PubMed1988

A modified method of DNA extraction from peripheral blood and bone marrow specimens.

We have outlined a modified method of DNA extraction from blood and bone marrow that can be used for gene rearrangement studies of leukemia and lymphoma and can consistently give excellent yields of DNA from as little as 1 x 10(6) cells. The method is based on the use of small sample vessels, a marked reduction in solution volume and minimal handling of the specimen. By using known cell numbers from eight leukemic bone marrow samples and four leukemic cell lines, the modified extraction procedure consistently had better yields of DNA, compared with a standard procedure. These findings were confirmed by further comparisons of DNA yields from 14 hypocellular clinical specimens that had been divided into two equal parts for side-by-side DNA extraction with both methods. The quality of the DNA from the modified extraction method was similar to standard methods on subsequent Southern blot analysis and hybridization with immunoglobulin and/or T-cell receptor gene probes. This modified DNA extraction method is a procedure that complements standard extraction methods and expands the number and type of specimens that can be evaluated by the clinical molecular genetics laboratory.

Blood Cell Count↗
PubMed1988

Expression and purification of protein segments encoded by the envelope and 3'-orf genes of human immunodeficiency virus type 1.

The pJL6 expression vector and its derivatives, pJLA16 and pANH-1, have been used for the synthesis and high-level expression in Escherichia coli of restriction enzyme fragments derived from the envelope and 3'-orf genes of the BH10 and BH8 clones, respectively, of the human immunodeficiency virus (HIV-1). These bacterially expressed proteins have been purified to apparent homogeneity by sequential detergent extraction, gel filtration, and reverse-phase high-performance liquid chromatography. The recombinant proteins have been used for the production of polyclonal and monoclonal antibodies, and the fusion proteins from the envelope gene are currently being evaluated for use as immunodiagnostic assay reagants.

Cloning, Molecular↗
PubMed1988

Mapping studies and expression of genes located on human chromosome 11, band q23.

Chromosome translocations and deletions may alter cellular proto-oncogenes and result in cellular changes that are important in the pathogenesis of malignancy. The region 11q23 is frequently involved in human malignancy. Utilizing a leukemic cell line with a reciprocal translocation involving 11q23 and somatic cell hybrids derived from this cell line, we analyzed five genes assigned to 11q23: NCAM, CD3D, CD3E, THY1, and ETS1. Our data showed no evidence of direct involvement of these genes in this leukemia but enabled a partial genetic map of this important region of the human genome to be constructed: 11cen--NCAM--CD3([G, D], E)--parallel--(ETS1, THY1)--11qter.

Animals↗
PubMed1988

Clonal rearrangement for immunoglobulin and T-cell receptor genes in systemic Castleman's disease. Association with Epstein-Barr virus.

Castleman's disease is a morphologically and clinically heterogeneous lymphoproliferative disorder. Both a localized benign variant and an aggressive form with systemic manifestations have been described. To investigate the differences between these variants of Castleman's disease, the authors analyzed lymph node DNA from 4 patients with the localized type and 4 with the systemic type of Castleman's disease for immunoglobulin and T-cell receptor gene rearrangements. The role of Epstein-Barr virus (EBV) and cytomegalovirus (CMV) was also studied by viral genomic DNA probes. They detected clonal rearrangements in 3 of the 4 patients with the systemic variant of Castleman's; no patients with localized disease had rearrangements. Copies of EBV genome were also detected in 2 of the 3 patients with clonal rearrangements. These results suggest that systemic Castleman's disease is a disorder distinct from the classical localized variant in that it may evolve into a clonal lymphoproliferation.

Adolescent↗