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Biomedical subjects

S Bilgrami

Publications and source records attributed to S Bilgrami.

41 records · Page 3Linked to original sources

A sequence-specific single-stranded DNA-binding protein that is responsive to epidermal growth factor recognizes an S1 nuclease-sensitive region in the epidermal growth factor receptor promoter.

An epidermal growth factor (EGF) responsive DNA-binding protein (ERDBP-1) has been identified. It recognizes with high affinity and specificity a specific single-stranded DNA sequence located in the S1 nuclease-sensitive site of the EGF receptor (EGFR) 5' flanking region. The EGF-responsive element, determined by footprint analysis, is located from -364 to -344 (86-106 base pairs upstream from the major in vivo transcription initiation site). The factor does not recognize the antisense DNA sequence or double-stranded DNA of the EGF-responsive element. Three bands were observed by mobility shift assay using nuclear extracts from normal human keratinocytes. UV cross-linking followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed one major band with molecular weight in the range of 121,000 to 128,000. The induction of ERDBP-1 became evident 3 to 4 h after EGF stimulation and remained elevated as long as EGF was present. HL60 cells are devoid of endogenous EGFR and produce no ERDBP-1. Retroviral gene transfer of EGFR into HL60 cells resulted in induction of ERDBP-1 by EGF to levels comparable to those found in human keratinocytes.

Base Sequence↗

Retroviral gene transfer of epidermal growth factor receptor into HL60 cells results in a partial block of retinoic acid-induced granulocytic differentiation.

HL60 cells are devoid of endogenous epidermal growth factor receptor (EGFR). They respond to retinoic acid and undergo terminal granulocytic differentiation. EGFR complementary DNA was introduced into HL60 cells by retroviral gene transfer. Scatchard plot showed that the binding characteristics are identical to those of A431 cells. HL60-EGFR cells were estimated to express 34,000 EGFR/cell (Kd = 5 nM). The tyrosine phosphorylation upon ligand binding is the first step of signal transduction. The dominant phosphotyrosyl proteins in epidermal growth factor-stimulated HL60-EGFR cells include a 170 kDa protein (EGFR itself), and 125 and 53 kDa proteins. The EGFR signal results in the induction of 92 kDa gelatinase/matrix metalloproteinase in HL60-EGFR cells, thereby providing evidence of the function of the exogenous EGFR and a semiquantitative measure of the EGFR signal. These HL60-EGFR cells offer a unique opportunity to examine the potentially important role of EGFR (c-erbB) in maintaining homeostasis between self-renewal and differentiation. c-erbB has been shown to play a physiological role in the self-renewal of the very early avian stem cells which do express EGFR. The v-erbB (double truncated EGFR) has been shown to cause avian erythroblastosis. We found that these HL60-EGFR cells responded to retinoic acid differently from the HL60-control cells. A partial block of only 45% granulocytic differentiation and concomitant proliferation was noted, consistent with a shift of balance between self-renewal and differentiation toward the former.

Cell Differentiation↗

Chemotherapy-induced nausea and vomiting. Easing patients' fear and discomfort with effective antiemetic regimens.

Patients receiving chemotherapy should be given optimal antiemetic therapy to maximize their comfort initially and to prevent development of delayed and anticipatory nausea and vomiting. Understanding the mechanisms of chemotherapy-induced nausea and vomiting allows the healthcare team to design drug regimens capable of avoiding these side effects. Prevention is important, because side effects can be debilitating and sometimes dose-limiting, and up to 10% of patients refuse chemotherapy altogether to avoid them. In general, combination antiemetic therapy is preferred over single-agent therapy for chemotherapeutic regimens that produce moderate to severe adverse effects.

Antiemetics↗

Capnocytophaga bacteremia in a patient with Hodgkin's disease following bone marrow transplantation: case report and review.

Capnocytophaga is a gram-negative, capnophilic, facultatively anaerobic bacillus that normally inhabits the oral cavity. We report the case of a patient who developed capnocytophaga bacteremia following autologous bone marrow transplantation for Hodgkin's disease, and we review other reported cases of capnocytophaga bacteremia in immunocompromised patients. In our case infection followed pretransplantation conditioning and was associated with severe oral mucositis and neutropenia. Antibiotic therapy resulted in clinical resolution of infection. Capnocytophaga bacteremia should be included in the differential diagnosis of febrile neutropenia in immunocompromised patients (e.g., those undergoing bone marrow transplantation) especially in the presence of mucositis and gingival bleeding.

Adult↗

Erythropoietin. Biology and clinical applications.

Erythropoietin is a glycoprotein hormone that plays a vital role in erythropoiesis. It is mainly produced in the fetal liver till the third trimester of pregnancy. At that point, the kidney interstitium takes over this function and becomes the main source of erythropoietin. Hypoxia stimulates erythropoietin production by a mechanism that may require a heme protein as a second messenger. Erythropoietin stimulates the maturation of erythroid precursors (colony-forming unit-erythroid and burst-forming unit-erythroid) via at least two types of cell surface receptors. The higher-affinity receptors appear to be more important in modulating the effects of erythropoietin in vivo. Changes in intracellular calcium may ultimately mediate the action of erythropoietin on erythroid precursors. A specific and sensitive radioimmunoassay is now available for accurately measuring erythropoietin levels. All forms of erythrocytosis except polycythemia vera are associated with elevated erythropoietin levels. Levels are also high in cord blood obtained following fetal asphyxia. Reduced levels are seen in patients with anemia due to renal diseases. The response of erythropoietin to the degree of anemia appears to be attenuated in patients with cancer, chronic diseases, and human immunodeficiency virus (HIV) infection. Erythropoietin has been successfully used for treating patients with anemia due to renal failure. Its use has also been approved for the treatment of anemia patients receiving zidovudine for HIV infection. Encouraging results have been observed when erythropoietin was used to treat anemia due to rheumatoid arthritis, hematological malignancies, and prematurity. It has also been used to increase the yield of autologous blood collected prior to an elective surgical procedure. However, it has not proved to be useful in sickle cell anemia and myelodysplastic syndromes.

Animals↗