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Biomedical subjects

A Saleem

Publications and source records attributed to A Saleem.

At least 55 records · Page 3Linked to original sources
PubMed1994

1-beta-D-arabinofuranosylcytosine activates serine/threonine protein kinases and c-jun gene expression in phorbol ester-resistant myeloid leukemia cells.

1-beta-D-Arabinofuranosylcytosine (ara-C) is an effective antileukemic agent that misincorporates into DNA. Recent studies have demonstrated that ara-C treatment is associated with transient induction of the c-jun early response gene. The present studies have examined the effects of ara-C on c-jun expression in a phorbol ester-resistant variant of the HL-60 myeloid leukemia cell line, designated HL-525, that is deficient in protein kinase C (PKC)-mediated signal transduction and fails to respond to 12-O-tetradecanoylphorbol-13-acetate with induction of c-jun transcripts. The results demonstrate that treatment of HL-525 cells with ara-C is associated with transcriptional activation of the c-jun gene. We also demonstrate that ara-C treatment is associated with activation of a PKC-like activity. Partial purification of this Ca(2+)-independent activity has demonstrated phosphorylation of synthetic peptides derived from (a) amino acids 4-14 of myelin basic protein and (b) the pseudosubstrate region of PKC (amino acids 19-31), with substitution of Ala25 with serine. The finding that the ara-C-induced activity is inhibited by the pseudosubstrate PKC(19-36) supports the activation of a PKC-like enzyme. Because PKC can act upstream of the mitogen-activated protein (MAP) kinases, we studied the effects of ara-C treatment on MAP kinase activity. The results demonstrate that MAP kinase is activated in ara-C-treated cells and that the kinetics of this activation are similar to those of the PKC-like activity. Because 12-O-tetradecanoylphorbol-13-acetate has little, if any, effect on the PKC-like and MAP kinase activities in HL-525 cells, these findings suggest that ara-C activates a distinct signaling cascade that may contribute to induction of the c-jun gene.

Cytarabine↗
PubMed1993

Activation of the early growth response 1 gene and nuclear pp90rsk in human myeloid leukemia cells by 1-(beta-D-arabinofuranosyl)cytosine.

The early growth response 1 (EGR-1) gene is induced by mitogens, differentiating stimuli, and certain genotoxic agents in diverse cell types. The present work has examined the effects of 1-(beta-D-arabinofuranosyl)cytosine (ara-C), an antileukemia agent that misincorporates into DNA, on EGR-1 expression. Treatment of HL-525 myeloid leukemia cells with ara-C was associated with transient increases in EGR-1 mRNA levels. Nuclear run-on assays showed that this effect is related at least in part to activation of EGR-1 gene transcription. Sequences responsive to ara-C-induced signals were determined by deletion analysis of the EGR-1 promoter. The results demonstrate that ara-C inducibility of the EGR-1 gene is conferred by a region containing six serum response or CC(A/T)6GG (CArG) motifs. Further analysis demonstrated that the first two distal or 5'-most CArG elements are functional in the ara-C response. An oligomer corresponding to the first CArG element also conferred ara-C inducibility of the minimal thymdine kinase gene promoter, while no inducibility was detectable using a similar oligomer containing a mutated CArG box. Other work has demonstrated that the nuclear serum response factor (SRF) interacts with the CArG box in the EGR-1 promoter and that the serine/threonine pp90rsk protein kinase phosphorylates SRF in vitro at sites phosphorylated in vivo. The present studies demonstrate that ara-C has little if any effect on cytosolic pp90rsk as determined by immunoblotting to assess electrophoretic mobility and by immune-complex kinase assays using S6 peptide as substrate.(ABSTRACT TRUNCATED AT 250 WORDS)

Base Sequence↗
PubMed1993

Defective translocation of protein kinase C in multidrug-resistant HL-60 cells confers a reversible loss of phorbol ester-induced monocytic differentiation.

Previous studies have demonstrated that human HL-60 myeloid leukemia cells differentiate in response to phorbol esters. This event is associated with induction of the c-jun early response gene and appearance of a monocytic phenotype. The present studies have examined the effects of vincristine-selected, multidrug resistance on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced HL-60 cell differentiation. The results demonstrate that multidrug-resistant HL-60 cells, designated HL-60/vinc, fail to respond to TPA with an increase in c-jun transcripts or other phenotypic characteristics of monocytic differentiation. By contrast, treatment of HL-60/vinc cells with okadaic acid, an inhibitor of serine/threonine protein phosphatases, induces c-jun transcription, growth arrest, and expression of the c-fms gene. Studies were also performed with an HL-60/vinc revertant (HL-60/vinc/R) line that has regained partial sensitivity to vincristine. The finding that HL-60/vinc/R cells respond to TPA with induction of a monocytic phenotype, but not c-jun expression, suggests that c-jun induction is not obligatory for monocytic differentiation. Other studies further demonstrate that the jun-B and fra-1 genes are induced by TPA in both HL-60/vinc and HL-60/vinc/R cells, whereas c-fos expression is attenuated in the HL-60/vinc line. Since TPA activates protein kinase C (PKC), we examined translocation of PKC from the cytosol to the membrane fraction. Although HL-60 and HL-60/vinc/R cells demonstrated translocation of PKC activity, this subcellular redistribution was undetectable in HL-60/vinc cells. Activity of the mitogen-activated protein kinase family with associated phosphorylation of c-Jun Y-peptide was markedly diminished in TPA-treated HL-60/vinc cells, but not in response to okadaic acid. Taken together, these findings suggest that vincristine resistance confers insensitivity to TPA-induced differentiation and can include defects in PKC-mediated signaling events and induction of jun/fos early response gene expression.

Calcium-Calmodulin-Dependent Protein Kinases↗
PubMed1990

Anemia of chronic disease: a review of pathogenesis.

Although anemia of chronic disease is a common hematologic disorder, the pathogenesis of the disease is still not well understood. Various workers have demonstrated decreased red cell life span, decreased erythropoietin levels, and inappropriate response of the bone marrow to the degree of anemia. The iron metabolism in the anemia of chronic disease is abnormal in that the macrophages in the bone marrow hold onto iron and do not release it for reutilization by the erythroid precursors. More recent studies have focused attention on cytokines produced by macrophages. These are interleukin-1 and tumor necrosis factor. These cytokines appear to be involved in both red cell production and ferrokinetics. Greater understanding of the biology of the cytokines may be the key to understanding the pathogenesis of anemia of chronic disease.

Anemia↗
PubMed1989

Thrombotic thrombocytopenic purpura: a brief review of recent literature.

Thrombotic thrombocytopenic purpura is a disease characterized by hemolytic anemia, thrombocytopenia, and neurological symptoms. Platelet thrombi in small vessels are formed as a result of endothelial injury or primary platelet aggregation or both. Etiology and pathogenesis, however, are not completely understood. Therapy, at one time nonexistent, has progressed to include plasma exchange, steroids, antiplatelet drugs, splenectomy, vincristine, and gamma globulin, thus improving the prognosis significantly over that of the mid-1960s.

Humans↗
PubMed1988

Fat overload syndrome. An autopsy study with evaluation of the coagulopathy.

Fat overload syndrome is a rare complication of intravenous fat emulsion therapy. It is characterized by sudden elevation of the serum triglyceride level, fever, hepatosplenomegaly, coagulopathy, and variable end-organ dysfunction. The illness is generally discrete, and symptoms regress as the lipemia clears. The transient nature of the syndrome has allowed only speculation as to its pathogenesis. The authors report an autopsy study of a child who died during an acute episode of fat overload and document the causative role of fat sludging in the associated end-organ failure. In addition, they offer evidence that the coagulopathy, previously an enigma, results from primary fibrinolysis, possibly caused by release of tissue plasminogen activators from the damaged endothelial cells.

Blood Coagulation Disorders↗
PubMed1988

T2 effect of hemoglobin concentration: assessment with in vitro MR spectroscopy.

T2 values were measured at 0.23 and 4.7 T for deoxygenated blood samples (43%-73% O2 saturation) with hematocrits of 18%-100%. An increase in the hematocrit produced a marked reduction in T2 at both field strengths. Cell lysis did not abolish the T2 effect at either field strength. The authors conclude that the increase in hemoglobin concentration caused by formation of a retracted clot is a cause of the hypointense appearance of acute hemorrhage compared with brain on T2-weighted clinical magnetic resonance images. This is particularly important on low-field-strength systems, which are not sensitive to the T2 shortening effects of paramagnetic intracellular deoxyhemoglobin.

Animals↗
PubMed1988

Methods for staining amyloid in tissues: a review.

The traditional way of identifying amyloid in tissue sections has been staining with Congo red and demonstration of green birefringence under crossed polarizers. The original method of Congo red staining, described by Bennhold in 1922, has undergone several modifications to improve its sensitivity, specificity, and reliability. The most common modification is the alkaline Congo red method described by Puchtler and co-workers in 1962. Specificity is improved by using freshly prepared stain and a staining solution fully saturated with sodium chloride. Amyloid proteins can be further distinguished by autoclaving or by treating the tissue with potassium permanganate or alkaline guanidine. Autoclaving the tissues at 120 C for 30 min causes protein AA to lose its affinity for Congo red. Prolongation of autoclaving to 120 min abolishes the Congophilia of protein AL, but prealbumin-related amyloid shows little or no change. Treatment of the tissue with potassium permanganate causes protein AA and B2-microglobulin amyloid to lose their affinity to Congo red. Protein AA fails to stain with Congo red after treatment with alkaline guanidine for 1 min and protein AL and systemic senile amyloid protein (SSA) after 2 hr. Familial amyloid protein (FAP), prealbumin type, can stand 2 hr of alkaline guanidine treatment without losing its ability to stain with Congo red. Other methods of detection of amyloid include fluorescent stains, e.g., thioflavin T or S, and metachromatic stains such as crystal violet. Immunofluorescence and immunoperoxidase methods are used to identify and classify amyloid proteins in tissues. Antibodies against the P component, proteins AA and AL and FAP have been used with great precision. Due to cross-reactivity, these methods do not differentiate between some types of familial and senile systemic amyloidosis.

Amyloid↗
PubMed1987

Suppression of hemoglobin H in disorders of iron metabolism.

Disorders of iron metabolism affect the expression of hemoglobin H in hemoglobin H disease. Two cases of iron deficiency with reduced synthesis of hemoglobin H are described in the literature. We report two more cases, one with anemia of chronic disease and another with alcoholic sideroblastic anemia where the hemoglobin H was not detected at presentation and appeared after treatment of the underlying disorder. The pathogenesis of suppression of hemoglobin H is discussed.

Adolescent↗
PubMed1985

Immune thrombocytopenia following alpha-interferon therapy in patients with cancer.

Immune thrombocytopenia occurred in five patients with cancer receiving alpha-interferon. The median pretreatment platelet count was 217,000/cu mm, which fell to a median of 12,000/cu mm after a median of 25 days of interferon therapy. All had normal numbers of megakaryocytes, with dysplasia noted in three; all four who were tested had platelet-associated immunoglobulin. All had normalization of platelet counts with prednisone therapy. Four tolerated re-treatment with interferon, two with concurrent prednisone administration and two others following splenectomy. Immune thrombocytopenia should be considered in patients who become thrombocytopenic during interferon therapy.

Adult↗
PubMed1984

Acute myelofibrosis. A report of four cases and review of the literature.

Four new cases of acute myelofibrosis are reported, and 63 cases reported in the literature are reviewed. The typical features of this disease include a rapidly progressive clinical course; nonspecific symptoms such as weight loss, anorexia, fatigue and weakness; the absence of organomegaly; pancytopenia; circulating blast cells; and mild abnormalities in the red blood cell morphology. The bone marrow aspirates are usually "dry." The bone marrow biopsies are essential for the diagnosis and show four consistent features: hypercellularity, reticulin fibrosis, proliferation of blast cells and bizarre, atypical megakaryocytes. In 16 cases, the blast cells in peripheral blood and bone marrow, which are unclassifiable by conventional morphology, could be identified as megakaryoblasts by ultrastructural and immunocytochemical techniques. It is concluded that acute myelofibrosis is a definite clinicopathologic entity, which may be related to acute megakaryoblastic leukemia.

Acute Disease↗
PubMed1983

Idiopathic thrombocytopenic purpura.

Idiopathic thrombocytopenic purpura occurs at all ages, in acute and chronic forms. Children mainly have the acute form, which usually follows a recent viral illness, occurs equally in both sexes, and generally resolves within six months. Chronic idiopathic thrombocytopenic purpura occurs more often in adults, often has an insidious onset, and shows a three:one female preponderance. Both forms are now thought to be due to an antiplatelet antibody, usually of the IgG class (platelet-associated IgG), which coats autologous platelets and leads to their phagocytosis and destruction by the reticuloendothelial system. In most patients, the spleen is the major site of the production of this platelet antibody and the destruction of the platelets. Many methods have been developed to detect this antiplatelet factor in the serum and on the platelets of patients with idiopathic thrombocytopenic purpura. Recent methods are becoming highly sensitive and may soon be simple and fast enough for routine clinical use and should significantly aid the diagnosis and management of these patients. Platelet-associated IgG levels appear significantly higher in patients with idiopathic thrombocytopenic purpura than in normal subjects, and in patients with nonimmune thrombocytopenia. Higher levels are also seen in children than in adults, and in acute cases than in chronic ones. Platelet-associated IgG levels also vary inversely with platelet count and platelet life span, can predict the disease course and response to therapy, and may predict neonatal consequences of maternal idiopathic thrombocytopenic purpura. Evidence of other alterations in immune status, as well as alterations in platelet function and HLA associations, remains controversial. Classic treatment with corticosteroids and splenectomy remains highly successful in most cases. More recent therapies include the use of immunosuppressants and alkaloid-coated platelets, plasma-exchange transfusion, and high-dose immunoglobulin. Overall, fewer than 5 percent of patients have severe hemorrhage or refractory or fatal disease.

Adrenal Cortex Hormones↗
PubMed1982

Erythroleukemia: a study of 15 cases and literature review.

Out of a total of 185 cases of acute leukemia at our institution from 1967 to 1978, fifteen cases (8.1%) were identified as erythroleukemia or erythremic myelosis. The symptoms at presentation were often related to anemia (10/15 cases); the presenting hemoglobin value was lower than 10.0 gm/100 ml. Nucleated red cells were present in the peripheral blood and reticulocyte response was inappropriate to the degree of anemia. Marrow biopsy showed erythroid hyperplasia with megaloblastic and dyserythropoietic features, increase in myeloblasts greater than 5% (10/15 cases), positive PAS staining of erythroid precursors (12/12 cases), and erythrophagocytosis by abnormal erythroid precursors (6/15 cases). Abnormalities were noted in monocytic and megakaryocytic cell lines, and it was concluded that erythroleukemia is probably a stem cell disorder. Response to chemotherapy was poor with median survival of four months from initial diagnosis. Intracranial hemorrhage and bacterial or fungal infection were the most frequent cause of death.

Adult↗
PubMed1982

Myelopathy following cervical spine manipulation.

Manipulation of the spine, a controversial mechanotherapeutic procedure, has been taught and practiced widely. Occlusion of vertebral, basillar, and cerebellar arteries with head and neck manipulation is well documented in the literature. However, there is a paucity of references about myelopathy associated with cervical spine manipulation. Three cases of cervical myelopathy following spinal manipulation are presented. All patients noted increase in cervical pain following manipulation, developed significant sensary/motor deficits within 24 hours and became tetraparetic. Two patients were found to have fracture of C5 and C6 vertebral bodies. On myelography, partial block was noted in all and widening of the spinal cord was noted in two. One patient underwent excision of C5 vertebral body and anterior interbody fusion C4/6. Two patients underwent cervical laminectomy. Hematomyelia was present in one, and in the other patient the spinal cord was reported to be hyperemic and oedematous. Only one patient showed neurological return and became ambulatory, while the other two remained tetraparetic.

Adult↗
PubMed1981

Prognostic factors and treatment effects on survival in erythroleukemia: a retrospective study of 134 cases.

A total of 134 cases of erythroleukemia (119 from the literature and 15 of the authors' patients) were reviewed in an attempt to correlate survival with age, sex, hepatomegaly, splenomegaly, lymphadenopathy, infection, or hemorrhagic complications at initial presentation; hemoglobin (Hgb), white blood cell (WBC) count, and platelet count; percent myeloblasts in the marrow at diagnosis; and treatment regimens employed. Statistical methods included single classification analysis of variance, nonparametric analysis of variance (Kruskal-Wallis method), contingency table analysis, and correlation coefficient determination for numerical data. No significant correlation between survival and age, sex, hepatomegaly, lymphadenopathy, infection, or hemorrhagic phenomena was found. Improved survival was noted in patients without splenomegaly, and in daunorubicin-treated cases in contrast to those treated with other chemotherapeutic agents. A positive correlation between survival and initial Hgb and WBC was also noted. Erythroleukemia complicating a chronic myeloproliferative disorder had a worse prognosis than de novo erythroleukemia.

Adult↗