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Biomedical subjects

A B Glassman

Publications and source records attributed to A B Glassman.

At least 37 records · Page 2Linked to original sources
PubMed1996

The biologic function of PML and its role in acute promyelocytic leukemia.

Patients with acute promyelocytic leukemia (APL) are characterized by the presence of a t(15;17) chromosomal translocation. The fusion protein PML-RAR alpha encoded from the breakpoint can form a heterodimer and acts as a dominant negative inhibitor against the normal function of PML. Recently we demonstrated that PML is a growth suppressor and transcription suppressor expressed in all cell lines tested. We also found that PML suppresses the clonogenicity and tumorigenicity of APL-derived NB4 cells, as well as the transformation of rat embryo fibroblasts by cooperative oncogenes and NIH/3T3 by neu. Overexpression of PML in human tumor cell lines induces a remarkable reduction in growth rate in vitro and in vivo. More recently, we have shown that PML is a phosphoprotein associated with the nuclear matrix and that its expression is cell cycle related. PML expression is altered during human oncogenesis, implying that PML may be an anti-oncogene involved not only in APL but also in other oncogenic events. Mutation analysis of the functional domains of PML demonstrated that its ability to form PML nuclear bodies or PODs (PML oncogenic domains) is essential for suppressing growth and transformation. In light of the above studies it appears that disruption of the normal function of PML plays a critical role in the pathogenesis of APL.

Animals↗
PubMed1996

[Changes in the cell cycle in breast cancer].

Recent advances in the mechanisms of oncogenesis have revealed a close relationship between the cell cycle and apoptosis. The cell cycle goes through a series of kinases and fosfatases activities that enhance the cyclins. In the mammalian cells, the kinases CDK4/6, CDK2, CDK2 and p34 are linked to the cyclins D, E, A, and B When the cell goes from the phase G1 toward mitosis. When the DNA is altered by intrinsic or extrinsic factors, the control checkpoints should stop the cycle in order to repair the damage. If the DNA cannot be repaired, apoptosis is induced. In cancer, the checkpoints do not function and the unstable genome of the cancer cell is repaired. Some of these changes occur in cancer of the breast and are discussed in this review.

Apoptosis↗
PubMed1995

Homozygous deletions at 8p22 and 8p21 in prostate cancer implicate these regions as the sites for candidate tumor suppressor genes.

Frequent loss of an allele at specific chromosomal regions implicates these regions as sites of tumor suppressor genes (TSG) that become inactivated during tumor progression. We have studied chromosome 8p allele losses in 32 primary human prostate carcinomas with 16 polymorphic microsatellite sequences. Overall, 22 of 32 (69%) informative specimens showed loss of allele in at least one locus. The most frequent losses of heterozygosity (LOH) occurred at the LPL locus (46%) on chromosome 8p22 and at the D8S360 (45%) and NEFL (43%) loci on chromosome 8p21. Homozygous deletions were detected at the LPL and NEFL loci at 8p22 and 8p21, respectively. The minimal region with frequent LOH and homozygous deletion, around the LPL locus, was restricted between the MSR locus and the D8S258 marker, separated by less than 9 cM. The second region was restricted between markers D8S1128 and D8S131 separated by 12 cM. The results suggest the existence of two chromosome 8p sites for candidate TSGs in prostate cancer.

Alleles↗
PubMed1995

der(1;15)(q10;10): a nonrandom chromosomal abnormality of myeloid neoplasia.

The occurrence of an unusual karyotypic abnormality der(1;15)(q10;q10) is reported in three patients, one with acute megakaryoblastic leukemia and two with myelodysplastic syndrome. A literature review shows that this cytogenetic abnormality is a rare but nonrandom change in myeloid neoplasia/neoplasia.

Aged↗
PubMed1995

Prophylactic versus therapeutic platelet transfusion practices in hematology and/or oncology patients.

BACKGROUND: Platelet utilization has steadily increased throughout the past three decades. At the same time, there has been very little study of the current transfusion practices. STUDY DESIGN AND METHODS: A survey was conducted of institutional members of the American Association of Blood Banks (hospitals) that were actively involved in the care of pediatric and/or adult hematology and/or oncology patients. Inquiries were made relating to the extent of prophylactic versus therapeutic use of platelets, criteria used for prophylactic transfusion of platelets and type, and dose of platelets used. Data were analyzed according to patient age and type of hospital. RESULTS: Of 786 responding hospitals, 630 (80.2%) provided sufficient data for analysis; 126 of that 630 provided care for pediatric patients. The majority (60.9%) of responding hospitals had a minimum of four hematologists and/or oncologists. Eighty-four percent of hospitals reported transfusing some apheresis platelets. The dose of platelet concentrates most frequently used for adults ranged from 6 to 10, with pools of 10 more commonly used in community hospitals. More than 70 percent of hospitals reported transfusing platelets primarily for prophylaxis: 60 percent of hospitals set the threshold platelet count for prophylactic platelet transfusion at 20,000 per microL, with approximately 20 percent each transfusing at higher and lower levels. A platelet count of 50,000 per microL was most frequently required for performance of a minor invasive procedure. CONCLUSION: The data from this study show that the majority of institutions use prophylactic platelet transfusion in both pediatric and adult hematology and/or oncology patients. However, there is considerable variation in platelet transfusion practice.

Adult↗
PubMed1995

Transfusion practices in human immunodeficiency virus-infected patients.

BACKGROUND: The reported immunomodulatory effects of transfusion raise concern about the potential for virus activation and tumor growth in human immunodeficiency virus (HIV)-infected patients. In the absence of "standards" of transfusion practice for such patients, a survey of transfusion policies among institutions specializing in the care of HIV-infected patients was performed to delineate current practices. STUDY DESIGN AND METHODS: A survey developed by the Transfusion Practices Committee of the American Association of Blood Banks was sent to 47 AIDS clinical trial units and 14 regional hemophilia centers in North America. RESULTS: Forty-three percent of centers completed the survey. Most centers observed more than 200 HIV-infected patients each. The key findings were that 1) 81 percent of centers used identical red cell transfusion criteria for HIV-infected and noninfected patients; 2) 52 percent used recombinant human erythropoietin as initial treatment for zidovudine-induced anemia, while 46 percent used recombinant human erythropoietin for anemia not associated with zidovudine; 3) 35 percent of centers used white cell-reduced blood components in lieu of cytomegalovirus (CMV)-seronegative components when administering transfusion(s) to CMV-seronegative patients; 4) 27 percent gamma-radiated cellular components, but no case of graft-versus-host disease had been observed; 5) > 85 percent of centers used monoclonal factor VIII for pediatric and adult hemophiliacs infected with HIV; 6) approximately one-third of centers routinely white cell-reduced cellular components; and 7) the most common reasons for white cell reduction included reduction of febrile reactions and CMV risk, reduction of platelet alloimmunization, and delay of immunomodulatory consequences of transfusion. CONCLUSION: There is marked heterogeneity in transfusion practice for HIV-infected patients. Modification of cellular components to achieve different objectives is routine in many centers.

Blood Transfusion↗
PubMed1986

Neutrophil agglutinins in idiopathic chronic neutropenia of early childhood.

Twelve patients with chronic neutropenia, ranging in age from 7 to 27 months, were studied for circulating antineutrophil autoantibodies. Absolute neutrophil counts ranged from 0 to 500/cu mm. None of the patients was transfused or had a history of prior drug ingestion. Edetic acid-microagglutination was employed to detect leukocyte antibodies. Sera from six of 12 patients contained antineutrophil antibodies, four reacting with neutrophils from the father and two from the mother. Patient sera also reacted with neutrophils of several unrelated normal volunteers. Four of the six patient sera with antineutrophil antibodies also reacted with autologous neutrophils. The duration of neutropenia was seven months in one patient with antibody whose neutropenia resolved. Patients with neutrophil autoantibody did not clinically differ from those without demonstrable antibody. The coexistent fall in leukoagglutinin titer and rise in neutrophil counts in one patient suggested an etiologic role for this antibody. Detection and proper diagnosis have important therapeutic implications.

Agglutination Tests↗
PubMed1986

Leishmania donovani: immunization against infection as a function of parasite growth phase.

C57BL/6 mice were immunized against Leishmania donovani infection with a subcutaneous vaccination protocol. Groups received 3 injections at 4-day intervals combining glucan and killed promastigotes harvested from either logarithmic or stationary phase cultures. Controls were immunized with glucan alone, stationary or log phase promastigotes alone, or were untreated. All groups were challenged intravenously with stationary phase promastigotes at day 45 post-immunization. Results revealed that animals immunized with the glucan-killed parasite vaccine, utilizing promastigotes derived from either log (GPL) or stationary phase cultures (GPS), demonstrated significant resistance against infection as compared to controls or untreated mice. Additionally, the reduction in hepatic amastigote proliferation in mice immunized with GPS was significantly greater than in mice immunized with GPL.

Animals↗
PubMed1986

Apheresis, exchange, adsorption and filtration of plasma: four approaches to the removal of undesirable circulating substances.

Plasmapheresis and plasma exchange have been widely used in the treatment of a variety of conditions, not always with a clear rationale. The most favorable results have been observed in the hyperviscosity syndrome and in a group of antibody-mediated diseases which includes post-infectious cold agglutinin disease, red cell aplasia, post-transfusion purpura, Goodpasture's syndrome, hemophilic patients with anti-factor VIII antibodies, and also in thrombotic thrombocytopenic purpura. In contrast, disappointing or conflicting results have been obtained in immune complex diseases, myasthenia gravis, cryoglobulinemia, etc. It seems likely that at least some of the difficulties may arise from the non-specific removal of a variety of substances as well as for our lack of understanding of immunological feed-back mechanisms which are disturbed by plasmapheresis and related techniques. Future developments are likely to be centered in the development of more specific approaches as based on filtration, affinity chromatography and adsorption to antibodies or other substrates. These approaches appear promising for the removal of "blocking factors" in patients with cancer, lipoproteins in patients with hypercholesterolemia, immune complexes, and toxic compounds. A cautiously optimistic approach to such new developments and their testing in animal models and in carefully controlled patient trials are essential. The principles on which these therapeutic approaches lie are valid, and the skepticism that surrounds them may be underserved, since it was largely the result of an indiscriminate use of non-selective procedures.

Adsorption↗
PubMed1985

A computerized system for the identification of alloimmune neutropenia in neonates.

In an attempt to determine the incidence of alloimmune neonatal neutropenia, a systematic study was initiated during a period of six months. Complete blood count, differential and absolute neutrophil count of all the newborns were determined to identify the newborns with neutropenia and those with persistent neutropenia were evaluated for the presence of maternal neutrophil antibodies. This resulted in the design and use of a computerized system which was successfully employed to identify several neonates born with this disorder. The system includes a main program and eight functional options, and is operated under a secret authority code so that patients' data are accessible only to the investigators. The major functional options are: create, display, update and delete a record for the newborn; display most recent neutropenic babies; search all records and display name and ID number; search all records for a given year and display data; and perform statistics. The statistical analysis includes the total number of babies, both normal and those with neutropenia, the total number of babies with neutropenia and with/without sepsis, and those with persistent neutropenia. Also included are the hematological data consisting of complete blood count and differential of all of the newborns. Several possibilities exist to expand and extend the program for additional research-related purposes.

Agranulocytosis↗
PubMed1985

Adoptive transfer of vaccine-induced resistance to Leishmania donovani.

BALB/c mice were immunized with three subcutaneous injections combining killed parasites and glucan, or were untreated. Spleen cells were transferred to syngeneic recipients. Mice which received 5 X 10(8) spleen cells from vaccinated donors demonstrated significant protection against Leishmania donovani challenge as compared to untreated mice receiving immune sera, or mice which received untreated spleen cells.

Animals↗
PubMed1985

Effects of ethyl alcohol on human peripheral lymphocytes.

Chronic alcoholics are more susceptible to infection and have increased incidences of certain types of carcinomas. One explanation for this may be suppressed immune responses secondary to ethyl alcohol consumption. This project was initiated to study the effect of ethyl alcohol on lymphocyte responses in vitro by monitoring tritiated thymidine uptake. Lymphocytes were incubated in the presence of phytohemagglutinin-P, concanavalin A, and pokeweed mitogen. The response of normal lymphocytes was noted after mitogen stimulation in the presence of ethyl alcohol in graded doses. Ethyl alcohol levels greater than or equal to 50 mg/dL suppressed tritiated thymidine uptake of normal lymphocytes for phytohemagglutinin-P and concanavalin A. Since ethyl alcohol exposure in concentrations consistent with blood levels that may be attained during routine ingestion significantly decreased lymphocyte blastogenesis, it is speculated that chronic ethyl alcohol ingestion may alter immune surveillance sufficiently to be responsible in part for the increased incidence of infection and/or neoplasms seen in alcoholic subjects.

Adult↗
PubMed1984

Antibodies to A19 and Bw35 complexes of human leukocyte antigens are present in infertile subjects with sperm antibodies.

Sera and secretions from 100 couples with unexplained infertility were tested for sperm antibodies by cytotoxicity and passive hemagglutination and also for antibodies to human leukocyte antigen (HLA) by cytotoxicity assays. Lymphocytes of the study subjects were typed for 61 HLA-A and B alleles. Thirteen of 30 (43%) men with sperm autoimmunity also had HLA antibodies in their serum and/or seminal plasma samples, in contrast to 2 of 35 (6%) nonautoimmune males (P = 0.0003). Twenty-five of 35 (71%) sperm antibody-positive infertile women had HLA antibodies in their sera and/or secretions, while only 7 of 31 (23%) women without sperm antibodies were positive (P = 0.00007). Antibodies to HLA-A19 (A26, A29, AW30, AW31, AW32, AW33, and AW34) and Bw35 (B5, B15, B17, and B18) complexes were present in 19 of 22 (86%) infertile men and 44 of 48 (92%) infertile women positive for HLA antibodies (P less than 0.01). The presence of antibodies to HLA-A19 and/or Bw35 in the infertile subjects did not correlate with the presence of HLA-A19 and/or Bw35 in the husbands. The presence of antibodies to HLA-A19 and/or Bw35 in the cervical mucus of the infertile women correlated with their presence in the seminal plasma of their husbands. It is suggested that antibodies to sperm antigens cross-reactive with HLA-A19 and/or Bw35 may be relevant to infertility.

Adult↗
PubMed1983

Automated erythrocytopheresis for relief of priapism in sickle cell hemoglobinopathies.

Priapism, a complication of male patients with sickle hemoglobinopathies, has been managed by a variety of surgical and nonsurgical forms of therapy that often are unsuccessful. The application of automated erythrocytopheresis (red blood cell exchange) by continuous-flow and semicontinuous-flow procedures appears to offer distinct advantages in the treatment of complications resulting from sickle hemoglobinopathies. The successful application of erythrocytopheresis for the relief of priapism in a patient with hemoglobin SC disease is presented and probably represents the first case reported on the use of automated red blood cell exchange procedures in the treatment of this condition. Data and results of automated erythrocytopheresis in 4 additional patients are presented. The advantages and disadvantages of erythrocytopheresis in the treatment of priapism (and other complications of sickle hemoglobinopathies) are discussed and the method is compared to other modes of therapy.

Adult↗
PubMed1982

Role of neutrophil antigen NA1 in an infant with autoimmune neutropenia.

A nontransfused 14-month-old female infant was investigated for persistent neutropenia of eight months' duration, with absolute neutrophil counts ranging from 410 to 935 cu mm. The patient's sera reacted with neutrophils from her own peripheral blood, from normal donors, and from her mother, all these having the neutrophil antigen NA 1, but not with neutrophils from NA 1-negative donors, including the father. The autoantibody was detectable by capillary agglutination and by indirect immunofluorescence techniques but not by complement-dependent cytotoxicity. No antibody was found in the mother's serum. Studies on three occasions showed good correlation between the appearance of circulating autoantibody and the peripheral neutrophil counts. Our observations, together with previously published reports, suggest a possible relationship of NA 1 antigen and the disease susceptibility of NA 1-positive infants to autoimmune neutropenia.

Agranulocytosis↗