PubMed Health⌕ Search

Biomedical subjects

M Shehata

Publications and source records attributed to M Shehata.

At least 19 recordsLinked to original sources
PubMed2006

Deregulated expression of fat and muscle genes in B-cell chronic lymphocytic leukemia with high lipoprotein lipase expression.

Lipoprotein lipase (LPL) is a prognostic marker in B-cell chronic lymphocytic leukemia (B-CLL) related to immunoglobulin V(H) gene (IgV(H))mutational status. We determined gene expression profiles using Affymetrix U133A GeneChips in two groups of B-CLLs selected for either high ('LPL+', n=10) or low ('LPL-', n=10) LPL mRNA expression. Selected genes were verified by real-time PCR in an extended patient cohort (n=42). A total of 111 genes discriminated LPL+ from LPL- B-CLLs. Of these, the top three genes associated with time to first treatment were Septin10, DMD and Gravin (P</=0.01). The relationship of LPL+ and LPL- B-CLL gene expression signatures to 52 tissues was statistically analyzed. The LPL+ B-CLL expression signature, represented by 64 genes was significantly related to fat, muscle and PB dendritic cells (P<0.001). Exploration of microarray data to define functional alterations related to the biology of LPL+ CLL identified two functional modules, fatty acid degradation and MTA3 signaling, as being altered with higher statistical significance. Our data show that LPL+ B-CLL cells have not only acquired gene expression changes in fat and muscle-associated genes but also in functional pathways related to fatty acid degradation and signaling which may ultimately influence CLL biology and clinical outcome.

Cohort Studies↗
PubMed2005

Warm ischemic time during laparoscopic live donor nephrectomy: effects on graft function.

BACKGROUND: Laparoscopic live donor nephrectomy (LDN) has become established as a safe and effective alternative to the open procedure. However, the effect of prolonged warm ischemia time (WIT) during retrieval of the kidney remains unclear. The aim of this study was to analyze the effects of WIT on short-term and long-term graft outcomes after LDN. METHOD: In this retrospective analysis of LDN the effects of WIT on delayed graft function, rate of decline in serum creatinine concentration (SCr) in the first 10 days, changes in SCr at 3 months, acute rejection rate changes in Delta creatinine, biopsy-proved chronic allograft rejection and graft survival were assessed according to duration of WIT. Analysis was made by comparing WIT < or =3 versus >3 minutes and WIT <5, 5-10, and >10 minutes. RESULTS: The WIT, which ranged from 1 to 15 minutes, appeared to be related to the learning curve and to technical difficulties. Prolonged WIT did not appear to have an effect on early graft function or the rate of decline in SCr during the first 3 months posttransplantation, but may be associated with an increased rate of acute rejection. Changes in Delta creatinine over time were not affected by the length of WIT during LDN. CONCLUSION: WIT encountered during LDN has no effect on either short-term or long-term graft outcome.

Acute Disease↗
PubMed2005

Routine use of renal-dose dopamine during living donor nephrectomy has no beneficial effect to either donor or recipient.

BACKGROUND: The use of dopamine as a renoprotective agent in kidney transplantation remains unclear. Some reports suggest that dopamine improves initial graft function and survival, while others have failed to demonstrate a beneficial effect. Our live-donor nephrectomy program is serviced by 2 senior anesthetists, one who routinely uses dopamine and the other who considers that current evidence does not support a renoprotective effect of dopamine in laparoscopic donor nephrectomy. PURPOSE: We aimed to study the renoprotective effect on donor and recipient renal function of renal-dose dopamine during laparoscopic live-donor nephrectomy (LDN). METHODS: A retrospective analysis was performed of 59 live donor and recipient pairs between 1999 and 2004. Donors were grouped according to whether they received dopamine infusion during LDN. All donors received Hartmann solution to maintain the central venous pressure at 12 mm Hg. The percentage change in serum creatinine (SCr) in both donors and recipients was compared at day 1, day 7, and week 6. RESULTS: In the donors, dopamine infusion had no effect on the mean percentage rise in SCr at day 1 or the mean percentage decrease in SCr at week 6. At day 7, however, patients who received dopamine had a significantly greater decrease in SCr compared with those who did not. In the recipients, there was no significant difference in the mean percentage decrease in SCr at days 1 or 7 or at week 6. Analysis at 1 year revealed no significant difference in sCr among the groups of donors and recipients. CONCLUSIONS: The intraoperative use of renal-dose dopamine during LDN seems to have no beneficial effect for either donor or recipient.

Creatinine↗
PubMed2005

The safety and efficacy of early withdrawal of calcineurin inhibitors in kidney transplant recipients 6 months' posttransplant.

INTRODUCTION: The introduction of calcineurin inhibitors (CNIs) in clinical transplantation has resulted in dramatic reduction in acute rejection rate and improvements in short-term allograft survival. However, CNI-induced chronic nephrotoxicity is a clinical concern since it is a major cause of chronic allograft failure. Recent studies suggest that withdrawal or reduction of CNI dosage results in improvement in graft function and survival. The aim of this study was to evaluate the safety and efficacy of substituting CNIs with mycophenolate mofetil (MMF) at 6 months' postkidney transplant. METHODS: Kidney transplant recipients of first or second grafts (n = 20) maintained on CNI-based therapy and with no history of irreversible acute or vascular rejection were included in the study. Primary end points were the incidence of biopsy-proven acute rejection or treatment failure. Secondary end points included changes in mean serum creatinine and estimated GFR (Cockroft and Gault, CG) over time, incidence of infection, cardiovascular risk factors (blood pressure, cholesterol), graft and patient survival rates, as well as incidence of biopsy-proven chronic allograft nephropathy (CAN). Study patients were compared to a matched control group (n = 20) who remained on CNI-based therapy at equivalent time points. RESULTS: Incidence of acute rejection following CNI withdrawal was 15%. All episodes reversed with steroid pulses. There was no significant difference in mean serum creatinine or estimated GFR during the follow-up period. No significant change occurred in blood pressure or antihypertensive agents between the groups; however, there was a trend toward lower cholesterol levels after CNI withdrawal. No graft or patient loss was seen during the study period. Biopsy-proven CAN was diagnosed in 2 control patients (10%) at 6 to 8 months' posttransplant. CONCLUSIONS: Withdrawal of CNI at 6 months following kidney transplantation is associated with an increased risk of rejection and a trend toward lower serum creatinine and cholesterol levels. Further follow-up is needed to establish the long-term results of CNI-sparing regimens on the development of CAN.

Blood Pressure↗
PubMed2005

Induction of apoptosis by proteasome inhibitors in B-CLL cells is associated with downregulation of CD23 and inactivation of Notch2.

Recently, proteasome inhibitors (PI) have attracted interest as novel anticancer agents in B-cell chronic lymphocytic leukemia (B-CLL). A prominent feature of B-CLL cells is the high expression of CD23, which is closely related to cell survival and is regulated by Notch2. Since several components of the Notch signaling cascade are tightly regulated by proteasomal degradation, we studied the effect of PI on Notch2 activity and CD23 expression. Exposure of B-CLL cells to PI led to induction of apoptosis, a time- and dose-dependent downregulation of CD23 expression and a decline in DNA binding of transcriptionally active Notch2. In contrast, the transcription factor NF-AT and its putative target gene CD5, which is highly expressed in B-CLL cells, were unaffected. When the late phase of PI-induced apoptosis was arrested by inhibition of caspase 3, the reduction of Notch2 activity was still observed, indicating that reduction of active Notch2 took place already during an earlier phase of apoptosis. Enforced expression of constitutively active Notch2 decreased PI-mediated apoptosis in a human B-cell line. These data indicate that downregulation of CD23 and loss of Notch2 activity are early steps in PI-induced apoptosis of B-CLL lymphocytes and may be part of the full apoptotic response.

Antigens, CD↗
PubMed2005

High expression of lipoprotein lipase in poor risk B-cell chronic lymphocytic leukemia.

We investigated the pattern of lipoprotein lipase (LPL) expression in B-cell chronic lymphocytic leukemia (B-CLL) and assessed its prognostic relevance. Expression of LPL mRNA as well as protein was highly restricted to leukemic B cells. The intensity of intracellular immunoreactivity of LPL was higher in samples of patients with unmutated immunoglobulin heavy-chain variable region genes (IGV(H)) compared to those with mutated IGV(H) genes. LPL mRNA levels in peripheral blood mononuclear cells (PBMNC) from 104 CLL patients differed by 1.5 orders of magnitude between cases with mutated (N=51) or unmutated (N=53) IGV(H) (median: 1.33 vs 45.22 compared to normal PBMNC). LPL expression correlated strongly with IGV(H) mutational status (R=0.614; P<0.0001). High LPL expression predicted unmutated IGV(H) status with an odds ratio of 25.90 (P<0.0001) and discriminated between mutated and unmutated cases in 87 of 104 patients (84%). LPL expression was higher in patients with poor risk cytogenetics. High LPL expression was associated with a shorter treatment-free survival (median 40 vs 96 months, P=0.001) and a trend for a shorter median overall survival (105 months vs not reached). Our data establish LPL as a prognostic marker and suggest functional consequences of LPL overexpression in patients with B-CLL.

Chromosome Aberrations↗
PubMed2005

Regulation of CD23 expression by Notch2 in B-cell chronic lymphocytic leukemia.

The original observation that sera from patients with chronic B-cell lymphocytic leukemia (B-CLL) contain high amounts of soluble CD23 (sCD23), which reflect disease activity and tumor load has been confirmed by numerous reports and serial determinations of sCD23 are now recognized as important indicators of disease progression. The reason why the leukemic cells over express CD23 and subsequently release large quantities of sCD23 as compared to healthy persons or patients with other lymphoproliferative disorders is still not clear. However, progress has been made in understanding the mechanism leading to the upregulation of CD23 in the leukemic cells. Following is an update on clinical data and a short review on the potential functions of CD23 as well as its regulation by Notch2 in B-CLL.

Cell Lineage↗
PubMed2004

Randomised double-blinded trial evaluating silymarin for chronic hepatitis C in an Egyptian village: study description and 12-month results.

BACKGROUND/AIMS: A double-blinded trial evaluating silymarin, an herbal supplement for liver disease, to prevent complications of chronic hepatitis C virus infection has not been done. SUBJECTS: One hundred and seventy-seven consenting residents of an Egyptian village with chronic hepatitis C virus were randomly assigned to receive either silymarin or multivitamin supplements. METHODS: Participants had baseline and follow-up clinical, ultrasound, blood tests and quality-of-life assessments. Community nurses visited weekly to ascertain compliance, distribute supplements and record adverse effects. RESULTS: At 12 months almost all of 141 remaining subjects reported feeling better, although symptoms and quality-of-life scores did not differ between the silymarin and multivitamin groups. Both the silymarin and vitamins were tolerated equally well; and >95% of supplements were taken by >95% of subjects. One in each group had no detectable hepatitis C virus antibodies while two in the silymarin group and three receiving multivitamins had undetectable hepatitis C virus RNA. Serum alanine aminotransferase elevations did not differ between groups. Serum hepatic fibrosis marker, hyaluronic acid and YKL-40, and abdominal ultrasound results were similar in both groups and may have progressed slightly at 12 months. CONCLUSIONS: The recommended dose of silymarin can be safely taken for 1 year and improves symptoms and general well-being, but has no effect upon hepatitis C virus viremia, serum ALT, or serum and ultrasound markers for hepatic fibrosis. More prolonged evaluation and a higher dose may be required to ascertain whether milk thistle supplements prevent complications of chronic hepatitis C virus.

Adult↗
PubMed2001

Evaluation of high-resolution pinhole SPECT using a small rotating animal.

UNLABELLED: Ex vivo measurements in animals are used frequently in the field of nuclear medicine for the characterization of newly developed radioligands and for drug development. In vivo SPECT would replace these ex vivo measurements in a relatively large number of cases if one were able to adequately image small organs. The pinhole collimator has been used extensively to obtain greater detail in planar imaging. However, using a pinhole collimator for SPECT is difficult because it requires a heavy collimated detector to rotate around a small object with a constant radius of rotation. METHODS: We have developed a mechanism in which the gantry and collimator are fixed and the animal rotates. Hollow cylinders of different sizes were made to enable imaging of small animals of different sizes: mice, hamsters, and rats. The cylinder is mounted on a stepping motor-driven system and positioned exactly above the pinhole collimator of an ARC3000 camera with a 1-mm pinhole insert. The stepping motor is controlled by the Hermes acquisition/processing system. After imaging each projection, a signal is given to rotate the stepping motor with the desired number of angular degrees. Filtered backprojection, adapted to pinhole SPECT, was used for reconstruction. The system allows adjustments of the radius of rotation and along the axis of the cylinder to select the field of view. Calibration experiments were performed to ensure that the axis of rotation was exactly in the middle of the cylinder. Phantom experiments were performed to assess sensitivity, spatial resolution, and uniformity of the system and to test the system for distortion artifacts. In addition, a brain dopamine transporter rat study and a hamster myocardial study were performed to test the clinical feasibility of the entire system. RESULTS: In the line source experiment, the spatial resolution obtained in air was 1.3 mm full width at half maximum, with a radius of rotation of 33 mm. Furthermore, the system has good uniformity and is capable of detecting cold spots of 2-mm diameter. The animal studies showed that it was feasible to image receptors or transporters and organs with sufficient detail in a practical setup. CONCLUSION: A rotating cylinder mechanism for pinhole SPECT is feasible and shows the same characteristics as conventional pinhole SPECT with a rotating camera head, without distortion artifacts. This mechanism permits pinhole SPECT to replace many ex vivo animal experiments.

3-Iodobenzylguanidine↗
PubMed2000

Reconstitution of endogenous interferon a by recombinant interferon in hairy cell leukemia.

Recombinant human IFN alpha (rhIFN-alpha) plays an important role in the treatment of hairy cell leukemia (HCL). However, the mechanisms leading to its beneficial effect are not completely clarified, and there is no information on IFN-alpha gene expression in this disease. Therefore, we investigated the pattern of IFN-alpha gene expression and protein production in HCL and their potential regulation by rhIFN-alpha. Blood samples from 10 patients with HCL and 8 healthy donors (HD) were investigated. Expression of IFN-alpha mRNA was assessed by reverse transcription-PCR analysis in peripheral blood mononuclear cells (PBMCs) under basal conditions and on induction with rhIFN-alpha and polyionosinic-polycytidylic acid [poly(I.C)]. IFN-alpha concentrations in plasma and culture supernatants were measured by immunoassays, and intracellular IFN-alpha was evaluated by fluorescence-activated cell sorting analysis. Results showed that, in contrast to blood samples from HDs, freshly isolated PBMCs from un treated HCL patients did not express IFN-alpha mRNA, whereas IFN-alpha transcripts were found in patients who were under rhIFN-alpha therapy Plasma of untreated patients contained no, or extremely low levels of IFN-alpha as compared with plasma of treated patients and HDs. Ex vivo treatment of PBMCs with rhIFN-alpha or poly(I.C) resulted in a remarkable up-regulation of IFN-alpha at the mRNA and protein level. In HCL, however the amounts of IFN-alpha protein remained less than in HD. Inhibition of IFN-alpha transcription was found after exposure of PBMCs to serum fron untreated patients. Finally, a reduced capacity to produce IFN-alpha was found within B- cell, T-cell, and monocyte compartments in HCL patients which could be enhanced by rhIFN-alpha. The results demonstrate the ability, of rhIFN-alpha to up-regulate the expression of IFN-alpha gene and protein production and suggest that priming the production of endogenous IFN-alpha is a critical step in the mechanism of action of rhIFN-alpha in HCL.

Aged↗
PubMed1999

Basic fibroblast growth factor is expressed by CD19/CD11c-positive cells in hairy cell leukemia.

Several features are characteristic for hairy cell leukemia (HCL). Among those are pancytopenia, bone marrow fibrosis, and the appearance of a defined tumor cell phenotype in peripheral blood (PB), bone marrow (BM), and spleen. Hairy cells (HC) coexpress antigens specific for B lymphocytes and monocytes/macrophages and thus the malignant cell does not seem to be restricted to a defined lineage. When serum or bone marrow aspirate was screened by enzyme-linked immunosorbent assay (ELISA) for basic fibroblast growth factor (bFGF), specimen derived from HCL (serum: mean value, 29 pg/mL; BM aspirate: mean value, 641 pg/mL) contained significantly higher levels than those from healthy subjects. To study whether peripheral blood mononuclear cells (PBMC) derived from patients suffering from HCL and healthy donors (HD) were capable of producing bFGF, culture supernatant (conditioned medium, [CM]) was tested for the presence of this cytokine. While bFGF was not detectable in cell cultures from HD, HCL-derived CM contained relatively high levels of bFGF. CM was successfully used for stimulation of mesenchymal cell proliferation, which could be inhibited by a neutralizing anti-bFGF antibody. Cellular activation by pokeweed mitogen (PWM) or the combination of 12-o-tetradecanoyl-phorbol-13-acetate (TPA) plus calcium ionophore (Ca-Ip) led to an enhanced mRNA expression. Results of Western blot experiments showed that HC synthesize at least three isoforms (approximately 18, 23, and 25 kD), but only the 23-kD isoform is exported. To assess the nature of the producer cell, double immunofluorescence analysis using a bFGF-specific and an anti-CD11c monoclonal antibody (MoAb) was undertaken. The majority of cells scoring positive for CD11c were also reactive with the anti-bFGF MoAb. Furthermore, enrichment of CD19/CD11c-positive cells correlated with enhanced bFGF levels, thereby supporting the argument for HC being the producer cells of bFGF. A biological function of bFGF in HCL might be mediation of chemoresistance, as 2-chlorodeoxyadenosine (2-CdA)-induced inhibition of cell proliferation can be reversed by bFGF. Endogenous bFGF production by HC is not affected by this purine analogue and 2-CdA-induced apoptosis is diminished in bFGF-producing HC as compared with normal PBMC. Therefore, bFGF expression by HC might be important for resistance to chemotherapy and survival of the malignant cells.

Aged↗
PubMed1999

Attitudes of surgical trainees towards transplantation surgery as a career.

At present there are a number of unfilled consultant posts in transplantation surgery in the United Kingdom, particularly within the field of kidney transplantation. Unless the current shortfall is addressed, it seems highly probable that the number of unfilled consultant posts will continue to increase. This survey aimed to highlight the reasons underlying trainees' reluctance to enter the field of transplantation surgery and to assess how the specialty might be changed to attract new trainees. Questionnaires were sent to 102 surgical trainees requesting details on age, sex, training grade, research interests and chosen specialty. They were asked to consider nine specified reasons commonly thought to influence a trainee's decision on whether or not he/she would enter their chosen specialty and to grade each of these according to their relative importance in the context of considering a career in transplantation. The survey then suggested five changes in training/structure, and the trainees were again asked to grade the relative importance of each with regard to whether it would attract them towards transplantation surgery. Replies were received from 61 trainees (60%). Trainees were deterred from transplantation surgery because of the on-call commitment, unpredictable workload, lack of exposure and a lack of information on the specialty. A reduced on-call commitment, increased income, increased exposure, improved training structure and increased information would all serve to attract new trainees to the specialty. To attract new trainees to transplantation surgery, there must be exposure to the specialty at an earlier stage in training, and a proactive stance must be adopted in providing information for the trainees. In addition, there needs to be ongoing commitment to improvements in training structure. The issues of increased income and an acceptable on-call commitment must be addressed.

Attitude of Health Personnel↗