Biomedical subjects

R L Sham

Publications and source records attributed to R L Sham.

26 records · Page 2Linked to original sources

PubMed1994

Use of cell surface antigen phenotype in guiding therapeutic decisions in chronic myelomonocytic leukemia.

The myelodysplastic syndromes are a heterogeneous group of hematopoietic stem cell diseases in which both diagnosis and prognosis are determined by cellular morphologic criteria. In some patients, prognosis is poor due to proliferation of immature cells, i.e. development of acute leukemia. An important clinical decision for patients with myelodysplastic syndromes is whether to treat with supportive care or to use cytoreductive drugs to control the proliferative component of these illnesses. Two cases of chronic myelomonocytic leukemia are presented where cell surface antigen phenotype analysis showed characteristics suggestive of proliferative disease and the patients were treated and obtained remission with cytoablative therapy. Cell surface marker analysis may be useful in guiding therapeutic decisions in myelodysplasia.

Aged↗

PubMed1994

Evaluation of mild bleeding disorders and easy bruising.

The diagnostic approach to easy bruising or a suspected mild bleeding disorder includes a careful history and physical examination as well as laboratory investigations. The history should determine whether or not a bleeding disorder exists and help elucidate possible causes. The physical examination should evaluate evidence of bleeding and identify systemic illness. The laboratory investigation should include both screening and more specific diagnostic tests depending on the results of the screening tests and clinical findings. The review will provide a framework for generating a differential diagnosis in patients with suspected bleeding disorders and will categorize them into abnormalities of coagulation factors, platelets and those related to blood vessels and supporting tissues.

Blood Coagulation Disorders↗

PubMed1993

Signal pathway regulation of interleukin-8-induced actin polymerization in neutrophils.

Interleukin-8 (IL-8), a recently described peptide cytokine, is a neutrophil chemoattractant and activator that exerts effects similar to fMLP, yet their receptors and their roles in pathophysiology differ. The effect of IL-8 on the neutrophil cytoskeleton has not been well studied; therefore, we compared and contrasted the effects of IL-8 and fMLP on neutrophil actin conformation and on the signal pathway regulation of actin responses. IL-8 caused a rapid, dose-dependent increase in neutrophil F-actin content within 30 seconds. The maximum increase was twofold. These changes were accompanied by the development of F-actin-rich pseudopods, as noted with fluorescence microscopy and scanning electron microscopy. Selected biochemical inhibitors were used to study the regulation of the IL-8-induced actin changes. Incubation of neutrophils with 2 micrograms/mL pertussis toxin resulted in a 67% inhibition of the IL-8-induced F-actin increase. The protein kinase C (PKC) inhibitors, staurosporine and H7, did not inhibit the increase in F-actin caused by IL-8. IL-8 caused a rapid increase in neutrophil intracellular calcium that could be completely inhibited by the chelating agent 1,2-bis(o-aminophenoxy)ethane-N,N-N',N'-tetraacetic acid (BAPTA). However, BAPTA-treated neutrophils retained the ability to increase F-actin in response to IL-8. Similar results were seen with fMLP, indicating that, similar to fMLP, the IL-8-induced actin response is mediated through pertussis-toxin-sensitive G-proteins but is neither dependent on PKC nor increases in cytosolic calcium. Thus, although IL-8 and fMLP exert their effects on neutrophils through different receptors, the signal transduction pathways used and the effects on actin conformation and pseudopod formation are similar.

Actins↗

PubMed1992

Burkitt cell leukemia with myelodysplasia as a presentation of HIV infection.

Hematologic manifestations of human immunodeficiency virus (HIV) infection include cytopenias, non-Hodgkin's lymphoma, and myelodysplasia. Acute lymphocytic leukemia has rarely been reported in association with HIV infection. We describe a patient who presented with Burkitt cell leukemia and myelodysplasia as her initial manifestation of HIV infection. The dysplastic features included circulating asymmetric binucleated red blood cells as well as pseudo Pelger-Huet cells. To the best of our knowledge, this has not been previously reported.

Adult↗

PubMed1991

Signal transduction and the regulation of actin conformation during myeloid maturation: studies in HL60 cells.

Maturation of human myeloid cells is associated with quantitative and qualitative changes in protein kinase C (PKC) and increases in N-formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP) receptors, actin, and actin regulatory proteins. We have studied the actin responses and cell shape changes caused by FMLP and its second messenger pathways in HL60 cells undergoing neutrophilic maturation. In uninduced cells, the PKC activators 12-O-tetradecanoyl phorbol-13-acetate (TPA), bryostatin, and 1-oleyl-2-acetylglycerol (OAG) resulted in 15% to 30% decreases in F-actin, whereas FMLP had no effect. Ionomycin had no effect on actin but did cause a 10-fold increase in intracellular calcium. Cells grown for 24 hours in 1% dimethyl sulfoxide (DMSO) acquired the ability to polymerize actin in response to FMLP and ionomycin. TPA continued to cause a decrease in F-actin at 24 hours, but caused an increase in F-actin at 48 to 72 hours of maturation. The PKC inhibitor 1-5-isoquinolinesulfonyl 2-methylpiperazine (H7) partially blocked the F-actin increase caused by TPA in induced cells, but had no effect on the decrease in F-actin caused by TPA in uninduced cells or the increase in F-actin seen in FMLP-treated neutrophils. F-actin rich pseudopods developed following TPA or FMLP stimulation of induced HL60 cells; in uninduced cells neither agent caused pseudopod formation but TPA caused a dramatic loss of surface ruffles. The ability of FMLP and ionomycin to elicit a neutrophil-like actin response in HL60 cells within 24 hours after DMSO treatment shows that the actin regulatory mechanism is mature by that time. The inability of ionomycin to increase F-actin in uninduced cells supports the view that calcium increases alone are insufficient for actin polymerization. The longer maturation time required for HL60 cells to develop an actin polymerization response to TPA compared with FMLP, coupled with the inability of H7 to block the FMLP-mediated F-actin increase in neutrophils, suggests that the F-actin increase caused by FMLP is not mediated solely by PKC. Lastly, the TPA-induced F-actin decrease and shape changes in uninduced HL60 cells, and the longer time required for a "mature" response to TPA, may reflect immaturity in the PKC isoenzyme pattern rather than immaturity of the actin regulatory mechanism.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

PubMed1990

Control of actin conformation in AML myeloblasts: the effects of bryostatin and TPA.

Protein kinase C (PKC), an enzyme involved in signal transduction, is the receptor for both the tumor-promoting phorbol esters and the anti-neoplastic bryostatins. In many cells, phorbol esters and bryostatins cause similar effects; we have found that both agents increase actin polymerization in neutrophils. In some cells, however, the two agents result in different cell processes; we have found consistently different effects of these agents on actin conformation in myeloblasts obtained from leukemic patients. The patients tested all had increases in F-actin in response to 12-O-tetradecanoylphorbol-13-acetate (TPA) and most had decreases in F-actin in response to bryostatin. The data suggests that leukemic myeloblasts have a different cytoskeletal response to a tumor promoter and an antineoplastic agent despite their common receptor.

Actins↗

PubMed1989

Progression of follicular large cell lymphoma to Burkitt's lymphoma.

Histologic progression of lymphoma into more aggressive cell types is well documented. We describe a patient who had the histologic and cytogenetic features of Burkitt's lymphoma after 15 years of therapy for follicular large cell lymphoma. To the best of our knowledge, this clinical progression with histologic and cytogenetic confirmation has not been reported.

Burkitt Lymphoma↗

PubMed1983

Fatty acid and glucose utilization in isolated, working fetal pig hearts.

Fatty acid uptake and the effects of long- and short-chain fatty acids on glucose utilization were assessed in isolated perfused fetal pig hearts (0.9 gestation) in which oxygenated nutrient buffer was pumped from both ventricles at controlled pressure (55 mmHg, mean arterial pressure) and heart rate (180 beats/min). When either 1.5 mM palmitate or 1.0 mM octanoate was added to buffer containing 10 mM glucose and insulin (100 microU/ml), glucose uptake, as measured by 3H2O production from D-[2-3H]glucose, was suppressed when compared with glucose uptake in the absence of fatty acid. Increased tissue concentrations of glucose 6-phosphate, fructose 6-phosphate, and citrate in hearts perfused with buffer containing octanoate indicated active beta-oxidation and inhibition of phosphofructokinase activity when compared with hearts perfused with glucose alone. In contrast, hearts perfused with buffer containing palmitate showed no increases in these metabolic intermediates. These results suggest that suppression of glucose uptake in the presence of long-chain fatty acid was not the result of phosphofructokinase inhibition but may result from inhibition of glucose transport by palmitate. Determinations of tissue concentrations of free carnitine and carnitine derivatives indicated that, although palmitate underwent esterification to long-chain acyl carnitine in the fetal heart, it failed to undergo extensive beta-oxidation.

Animals↗