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Biomedical subjects

R S Verma

Publications and source records attributed to R S Verma.

At least 145 records · Page 8Linked to original sources
PubMed1991

del(2)(p23): a consistent recurrent abnormality in acute myelogenous leukemia.

A case of acute myelogenous leukemia (AML-M2) with an unusual chromosomal finding is presented. In addition to the most frequently observed translocation in this neoplasia, involving the long arms of chromosomes 8 and 21, there was a partial deletion of the short arm of chromosome 2 band (p23), i.e., 46,XX,del(2)(p23),t(8;21)(q22;q22). Deletion of the short arm of chromosome 2 has been described in association with other chromosome abnormalities in two other cases of AML and as the sole abnormality in three cases of AML, indicating that this abnormality is nonrandom and may be associated with leukemic transformation of hematopoietic cells. Therefore, we propose that the del(2)(p23),t(8;21)(q22;q22) abnormality be accorded status III and possibly considered a subset of AML (M2).

Adult↗
PubMed1991

Chromosomal abnormalities in childhood acute nonlymphocytic leukemia (M4).

A new reciprocal, apparently balanced translocation between chromosomes 7 and 22, i.e., t(7;22)(p22;q13), in association with inv(16)(p13q22) in a child with acute nonlymphocytic leukemia (M4) is reported. Five percent of her bone marrow cells contained both of these aberrations while 90% of her cells have the pericentric inversion of chromosome 16 as the sole abnormality. A clonal evolution of the unusual cell line may be associated with atypical clinical presentation. The presence of inversion 16 in adults has a better prognosis as compared with children. A concise review on the cytogenetic findings in children with ANLL(M4) is also provided.

Child↗
PubMed1991

Heteromorphisms of pericentromeric heterochromatin of chromosome 19.

The pericentromeric heterochromatin of chromosome 19 exhibits considerable variation even by the G-banding technique. Nevertheless, the C-banding technique has been universally employed to investigate pericentromeric hetromorphisms. We demonstrate that optimal expression of the pericentromeric region can be achieved by using the AluI/G technique. The pericentromeric heterochromatin of chromosome 19 is classified into four classes (I-IV). Fifty normal individuals were evaluated and the incidence of types I-IV were 26%, 17%, 51%, and 6%, respectively. No consistent relationship was observed between the types of heterochromatin identified by the AluI/G technique when compared with the other routinely used procedures.

Chromosome Banding↗
PubMed1991

Enhancement of amniotic fluid cell growth for genetic amniocentesis.

The last two decades have witnessed a logarithmic growth in demand for prenatal diagnosis of human disease through amniocentesis. Consequently, culture turn-around-time has become the major concern of all those who are primary care providers for patients seeking help. We report a rapid method for obtaining cytogenetic results from amniocytes as early as 5 days. Early tapping and reducing the turn-around-time during cytogenetic analysis may provide an alternative to chorionic villi sampling.

Amniocentesis↗
PubMed1991

Megaloblastic hematopoiesis in vitro. Interaction of anti-folate receptor antibodies with hematopoietic progenitor cells leads to a proliferative response independent of megaloblastic changes.

We tested the hypothesis that anti-placental folate receptor (PFR) antiserum-mediated effects on hematopoietic progenitor cells in vitro of increased cell proliferation and megaloblastic morphology were independent responses. We determined that (a) purified IgG from anti-PFR antiserum reacted with purified apo- and holo-PFR and specifically immunoprecipitated a single (44-kD) iodinated moiety on cell surfaces of low density mononuclear cells (LDMNC); (b) when retained in culture during in vitro hematopoiesis, anti-PFR IgG (in contrast to PFR-neutralized anti-PFR IgG and nonimmune IgG) consistently led to increased cloning efficiency of colony forming unit-erythroid (CFU-E), burst forming unit-E (BFU-E), CFU-granulocyte macrophage (CFU-GM), and CFU-GEM megakaryocyte (CFU-GEMM), and objectively defined megaloblastic changes in orthochromatic normoblasts from CFU-E- and BFU-E-derived colonies; (c) when anti-PFR antiserum was removed after initial (less than 1 h) incubation with LDMNC, a cell proliferation response was induced, but megaloblastic changes were not evident. (d) Conversely, delay at 4 degrees C for 24 h before long-term plating with antiserum resulted in megaloblastosis without increased cell proliferation; (e) however, 500-fold molar excess extracellular folate concentrations completely abrogated the expected anti-PFR antiserum-induced megaloblastic changes, without altering cell proliferative responses. Thus, although cell proliferative and megaloblastic changes are induced after short-term and prolonged interaction of antibody with folate receptors on hematopoietic progenitors, respectively, they are independent effects.

Animals↗
PubMed1991

Densitometric analysis of Southern blot autoradiographs and its application to monitoring patients with chronic myeloid leukemia.

The characteristic genetic exchange in chronic myeloid leukemia (CML) is the fusion of the ABL proto-oncogene and a specific part of the BCR or phl gene. Detection of this exchange by cytogenetic or Southern blot analysis is highly diagnostic for CML. The latter approach has not previously been used to quantify the relative proportions of leukemic and non-leukemic cells. We have assessed the feasibility of estimating the relative proportion of leukemic cells present in a sample by densitometric analysis of autoradiographs of Southern blots. In dilution experiments of CML cells with normal cells, a linear relationship could be demonstrated between the relative intensity of the autoradiograph band corresponding bcr rearrangement and the proportion of leukemic cells present. This relationship was found to be largely independent of autoradiograph exposure time. Six patients receiving various therapies have been evaluated for as long as 4.5 years by repeated densitometric and cytogenetic analysis. In general, a declining proportion of Philadelphia (Ph) chromosome positive cells was paralleled by decreasing intensity of the autoradiograph band representing bcr rearrangement. Densitometric changes were often seen prior to the detection of Ph negative cells. This analysis appears to provide a sensitive method for monitoring patients with CML.

Autoradiography↗
PubMed1990

Recombinant gamma-interferon has activity in chronic myeloid leukemia.

We demonstrated the clinical effectiveness of recombinant interferon-gamma (rIFN gamma) (Biogen) in 18 patients with Philadelphia-positive chronic myeloid leukemia. Sequential cytogenetic studies and molecular analyses of the breakpoint cluster region and for immunoglobulin and T cell rearrangements were performed every 3-4 months. In 13 patients who received treatment for a minimum of 3 months, the majority were treated with 1.5 mg/m2, t.i.w., i.v. Nonhematologic effects--particularly chills, rigors, myalgia, fatigue, headaches, and nausea--were significant. Complete or partial hematologic responses were observed in six patients, two of whom had approximately 20% normal metaphases after an average of 74 weeks of treatment. However, reversion to 100% Ph+ cells occurred 30 weeks later. In these two patients, in whom normal metaphases were found, no changes were observed in the presence of rearrangements of the breakpoint cluster region. In addition, the marrows remained hypercellular, and the leukocyte alkaline phosphatase score and B12 levels remained abnormal. No immunoglobulin or T cell beta-chain gene rearrangements were found. These data indicate the clinical effectiveness of rIFN gamma in some patients with chronic myeloid leukemia, although the fundamental nature of the disease is unaltered by this form of treatment.

Bone Marrow↗
PubMed1990

The Coffin-Siris syndrome.

We report a white female infant with typical features of Coffin-Siris syndrome including thick eyebrows, flat nasal bridge, anteverted, wide nose tip, generalised hypertrichosis, scalp hypotrichosis, absence of the fifth fingernails and toenails, absence of the distal phalanges of the fifth fingers and of the second to fifth toes, small patellae, inguinal hernia, and sucking and feeding difficulties. There was decreased fetal activity and intrauterine growth retardation.

Female↗
PubMed1990

Spatial relationship between Ph and normal chromosome 22 at somatic metaphase in chronic myelogenous leukemia.

The spatial distances between the Ph and the normal chromosome 22 in bone marrow are compared with the distances between the two normal chromosome 22s in peripheral blood. No significant differences between these two distances were found in two different tissues. The present findings indicate that length does not affect the spatial relationship between the homologous chromosomes in the nucleus, as previously postulated.

Chromosomes, Human, Pair 22↗
PubMed1990

Anatomy of human genome by restriction endonucleases Alul, Ddel, Haelll, Hinfl, Mobol and Rsal, and their application in clinical cytogenetics.

The application of restriction endonucleases Alul, Ddel, Haelll, Hinfl, Mbol and Rsal in clinical cytogenetics is described. The extensive inherent heterogeneity of heterochromatin in the C-band regions revealed by these enzymes provides a valuable tool for describing the origin of trisomies and abnormal chromosomes in humans. The heteromorphic markers identified by these enzymes have tremendous potential in clinical cytogenetics. Unlike the CBG technique, slides can be stained immediately after preparation providing a rapid diagnosis. Characteristic bands induced by each enzyme in the human complement are discussed in detail. Comparative analysis of the present data, with those described earlier, revealed certain discrepancies including chromosomes 19 and 20 by Alul, chromosomes 4, 5, 8 and 22 by Mbol and chromosomes 12 and 20 by Rasl. These controversies are examined in the light of heteromorphisms, technical variables and chromosome identification.

Chromosome Banding↗
PubMed1989

Folate (pteroylglutamate) uptake in human red blood cells, erythroid precursors and KB cells at high extracellular folate concentrations. Evidence against a role for specific folate-binding and transport proteins.

Membrane-associated folate (pteroylglutamate, PteGlu)-binding proteins (FBPs) play an important role as PteGlu-transport proteins in malignant and normal human cells. Since high extracellular folate (PteGlu) concentrations (EFC) profoundly influenced uptake and toxicity of the anti-PteGlu methotrexate in malignant KB cells, we studied human cells to determine additional mechanisms for PteGlu uptake when the EFC was varied. At low EFC (less than 10 nM), the predominant mechanism for folate uptake in mature erythrocytes was through binding to externally oriented FBPs which were quantitatively insignificant (4-6 orders of magnitude lower) and of no apparent physiological relevance when compared with KB cells. However, the predominant mechanism of PteGlu accumulation at high EFC [10-250 nM] in intact erythrocytes and sealed right-side-out (RSO) ghosts was not FBP-mediated and non-specific. This conclusion was based on the findings that radiolabelled PteGlu uptake: (i) continued even in the presence of a 1000-fold excess of unlabelled PteGlu and was linear and not saturable up to 250 nM; (ii) was two-fold higher at pH 4.5 than 7.5; (iii) was less than 2-fold increased at 37 degrees C compared with 4 degrees C; and (iv) was unaffected after trypsin-mediated proteolysis of greater than 75% FBPs. The [3H]PteGlu and 125I-PteGlu (histamine derivative) accumulated intracellularly through the non-specific PteGlu-uptake mechanism was unaltered biochemically and in a soluble compartment. Raising the EFC 500-fold higher than controls during erythropoiesis in vitro resulted in reversal of the expected anti-(placental folate-receptor)-antiserum-induced megaloblastic changes in orthochromatic normoblasts derived from burst-forming unit-erythroid colonies. Furthermore, at EFC greater than 0.1 microM, KB-cell accumulation of [3H]PteGlu was also predominantly through a mechanism that did not involve specific FBPs. Thus, at high EFC, a major component of PteGlu transport in human cells is not mediated through FBPs and is likely to be a passive diffusion process.

Carrier Proteins↗
PubMed1989

Hydrophobic erythrocyte folate binding proteins are converted to hydrophilic forms by trypsin in vitro.

Human erythrocyte membranes contain high-affinity folate-binding proteins (FBPs) which on solubilization with detergents resolve into apparent 160,000 Mr moieties on Sephacryl S-200 gel filtration in Triton X-100. These FBPs share antigenic and ligand binding characteristics with particulate FBPs from other human tissues. During studies to define the vectorial orientation of these FBPs on the erythrocytes, we trypsinized intact cells with 250 micrograms trypsin per ml packed cells and quantitatively analysed the remaining cell-associated FBPs as well as the products of proteolysed FBPs in the supernatant. Incubation of intact cells with trypsin resulted in a dose-dependent decrease in their capacity to bind 125I-labelled pteroylglutamate (histamine derivative); at 250 micrograms/ml trypsin, folate binding was decreased by 77% compared to nontrypsin-treated control cells. While trypsinized cells contained proportionately lower quantities of apparent 160,000 Mr FBPs than untreated control cells, the supernatant of trypsinized cells (soluble phase) contained a single species of Mr = 40,000 which retained folate binding capacity. The sum of FBPs in trypsin supernatant and trypsin-treated cells was 87% of that found in untreated cells. Analysis of solubilized particulate erythrocyte FBPs and soluble (trypsin product) FBPs by sucrose density gradient ultracentrifugation in H2O and 2H2O above the critical micellar concentration of Triton X-100 revealed that apparent 160,000 Mr FBPs were detergent-binding (hydrophobic) species (which sedimented at Mr = 40,000 in H2O) while soluble FBPs (also sedimenting at Mr = 40,000) were hydrophilic and did not bind Triton X-100. These are the first data which show that hydrophobic FBPs can be directly converted to hydrophilic FBPs by a trypsin-mediated proteolytic event. The trypsin-sensitive site is likely to be at the junction between the detergent-binding site and the major body of the protein (Mr = 40,000) containing the folate binding site.

Biological Transport↗