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Biomedical subjects

A Raafat

Publications and source records attributed to A Raafat.

At least 19 recordsLinked to original sources
PubMed2007

Development of leiomyosarcoma of the uterus in MMTV-CR-1 transgenic mice.

Overexpression of Cripto-1 (CR-1) in FVB/N mice using the MMTV-LTR promoter results in increased mammary tumourigenesis in these female transgenic mice (MMTV-CR-1). Here, we characterize uterine tumours that developed in 15/76 (19.7%) of MMTV-CR-1 female nulliparous or multiparous mice during 24 months of observation compared with 0/33 (0%) of FVB/N normal control mice observed during the same time period (p < 0.01). The uterine tumours collected from the MMTV-CR-1 mice were classified as leiomyosarcomas and found to express the CR-1 transgene by polymerase chain reaction analysis and immunohistochemistry. Detection by western blot analysis showed higher levels of phosphorylated (P) forms of c-src, Akt, GSK-3beta, and dephosphorylated (DP)-beta-catenin in lysates from MMTV-CR-1 uterine leiomyosarcomas in comparison with lysates from normal control FVB/N uteri. Immunostaining showed increased nuclear localization of beta-catenin in the MMTV-CR-1 uterine leiomyosarcomas. Increased immunostaining for CR-1 was detected in 9/13 (69.2%) cases of human leiomyosarcoma compared with staining in 3/15 (20%) human leiomyoma sections. Stronger immunostaining for P-src, P-Akt, P-GSK-3beta and increased nuclear localization of beta-catenin was also seen in human leiomyosarcomas in comparison with leiomyomas. Normal human uterine smooth muscle (UtSM) cells treated with exogenous soluble rhCR-1 showed increased levels of P-src, P-Akt, P-GSK-3beta and dephosphorylated (DP)-beta-catenin and increased proliferation (p < 0.05) and migration (p < 0.01) in comparison with untreated control UtSM cells. Inhibitors against c-src, Akt or beta-catenin, individually or in combination, significantly reduced CR-1-induced migration. These results suggest a role for CR-1 during uterine tumourigenesis either directly by activating c-src and Akt and/or via cross-talk with the canonical Wnt signalling pathway, as suggested by the increased expression of P-GSK-3beta, DP-beta-catenin, and increased nuclear localization of beta-catenin in human and MMTV-CR-1 mice leiomyosarcomas.

Animals↗
PubMed2006

Kit and PDGFR-alpha activities are necessary for Notch4/Int3-induced tumorigenesis.

Transgenic mice overexpressing Notch4 intracellular domain (Int3) under the control of the whey acidic protein (WAP) or mouse mammary tumor virus-long terminal repeat promoters, develop mammary tumors. Microarray analysis of these tumors revealed high levels of c-Kit expression. Gleevec is a tyrosine kinase inhibitor that targets c-Kit, platelet-derived growth factor receptors (PDGFRs) and c-Abl. This led us to speculate that tyrosine kinase receptor activity might be a driving force in the development of Int3 mammary tumors. WAP-Int3 tumor-bearing mice were treated with continuous release of Gleevec using subcutaneously implanted Alzet pumps. Phosphorylation of c-Kit, PDGFRs and c-Abl is inhibited in Int3 transgenic mammary tumors by Gleevec. Inhibition of these enzymes is associated with a decrease in cell proliferation and angiogenesis, and an induction of apoptosis. To examine the signaling mechanisms underlying Notch4/Int3 tumorigenesis, we employed small interfering RNA (siRNA) to knock down c-Kit, PDGFRs and c-Abl alone or in combination and observed the effects on soft agar growth of HC11 cells overexpressing Int3. Only siRNA constructs for c-Kit and/or PDGFR-alpha were able to inhibit HC11-Int3 colony formation in soft agar. Our data demonstrate an inhibitory effect of Gleevec on Int3-induced transformation of HC11 cells and mammary tumors and indicate an oncogenic role for c-Kit and PDGFR-alpha tyrosine kinases in the context of Int3 signaling.

Animals↗
PubMed2001

Notch signaling in mammary gland tumorigenesis.

The Notch receptor protein and its signaling pathway have been well conserved throughout evolution and appear to be pivotal components in cell fate decisions during development. Recent studies suggest that, depending on the cellular and developmental context, Notch signaling may also affect cell proliferation and programmed cell death. Mammals have four related Notch genes. One of these, designated Notch-4, was found to be a common integration site for the mouse mammary tumor virus in mouse mammary tumors. One consequence of this type of viral integration event is the ectopic expression of the intracellular domain of Notch-4 that corresponds to a gain-of-function mutation. Expression of "activated" Notch-4 in mammary epithelium has profound effects on mammary gland development and tumorigenesis. In this review, we briefly summarize the structure and function of the Notch receptor, as well as the components that comprise and modify the signaling pathway. Finally we discuss the potential role of Notch in mammary gland development and tumorigenesis.

Animals↗
PubMed2001

A simple, highly sensitive and improved method for the measurement of bleomycin-detectable iron: the 'catalytic iron index' and its value in the assessment of iron status in haemochromatosis.

In the presence of ferrous ions (Fe(2+)), the anti-tumour agent bleomycin will induce DNA degradation. Degradation of DNA into substances detectable by the thiobarbituric acid test has been used previously for the detection of iron in a form that is capable of catalysing the formation of the potentially harmful hydroxyl free radical. In the present paper, we describe the application of the ethidium-binding assay of DNA damage to the measurement of bleomycin-detectable iron, comparing its performance with the conventional method in the assessment of iron standard solutions and plasma samples from haemochromatosis patients. The ethidium-binding assay proved to be more responsive than the thiobarbituric acid test in the detection of DNA damage induced by very low concentrations of iron, but became saturated at higher iron concentrations. Agreement between the two versions of the assay in the identification of plasma samples containing bleomycin-detectable iron was good, but agreement on the actual concentrations of such iron in the positive samples was poor. This discrepancy is believed to be due to interference with the thiobarbituric acid assay by plasma. Consequently, it was not possible to obtain reliable estimates of free iron concentrations in plasma when using the conventional version of the bleomycin assay. We have devised a parameter of iron status called the catalytic iron index. For healthy, non-haemochromatotic individuals, the mean value of this parameter was found to be 0.81 (range 0.78-0.84; n=20). Elevated values were observed in some plasma samples from haemochromatosis patients, but these showed no correlation with serum ferritin levels. In contrast, correlations were seen with both serum iron and transferrin saturation levels, but only when these were above the normal range.

Antimetabolites, Antineoplastic↗
PubMed2000

Current management of pelvic fractures.

Blunt pelvic injuries are becoming more common in this era of high-speed, high-energy collisions. At least 5% of blunt injuries result in pelvic fracture. With mortality rates approaching 55% for severe crush injuries of the pelvis, early stabilization and control of bleeding, as well as assessment for other injuries, requires a focused, multidisciplinary approach. We discuss early management and stabilization of severe pelvic fractures.

Accidents, Traffic↗
PubMed1998

Benefit of dynamic over static incubation in the detection of a low-level HBsAg (chronic carrier) bone donor.

BACKGROUND: Hepatitis B infection can be transmitted by organ or tissue transplantation. CASE REPORT: A 40-year-old man received a bone graft from a donor who tested negative for HbsAg with a static-mode assay. The same donor, on a subsequent donation, was found to be HbsAg-positive with a dynamic mode assay. The archival sample from the initial donation also tested HbsAg-positive with the dynamic-mode assay. The recipient of the bone, who had received HBV vaccine in the past, did not develop clinical or laboratory evidence of HBV infection. CONCLUSIONS: This case highlights the importance of sensitive microbiological test protocols in the context of tissue banking.

Adult↗
PubMed1997

Infection associated with the use of allograft bone from the north east Scotland Bone Bank.

To assess the rate of infection associated with use of banked allograft bone, the case records of patients receiving banked bone over one year were reviewed. The notes of patients undergoing autografting procedures during the same period were reviewed as controls. Eighty-two patients received 98 banked allograft femoral heads and there were 10 proven infections (12.2%). Fifty-seven patients had autograft procedures, with two cases of infection (3.5%). The results of bacteriological surveillance of grafts harvested during the same period were analysed; there was a discard rate due to bacterial contamination of 1.3%, and two patients received three contaminated grafts, one of these patients suffering a postoperative infection. The failure rate of procedures was 50% where there was postoperative infection and 4.2% where there was none. Procedures using banked allograft bone have a substantial infection risk, and this is associated with a much higher rate of failure of the procedure. Prospective audit of allograft use should be applied to reduce this risk.

Bone Banks↗
PubMed1997

A quality assurance scheme for the Kleihauer test: the Scottish experience 1988-1996.

This report describes the experience gained in the last 8 years of implementing and administering a Quality Assurance Scheme dedicated to improving the reliability of Kleihauer test results in Scotland. Initially the five transfusion centres in Scotland were the only participants, but since 1992 all 15 hospital laboratories in Scotland performing the Kleihauer test to ensure an adequate dose of anti-D is administered to Rh-negative women, at risk of developing allo anti-D, have joined this voluntary scheme. As a result of the standardization of technical methods, improvement in reporting of QA results has been observed since 1994.

Feedback↗
PubMed1993

Serum enzyme activities in individuals with different levels of physical fitness.

Serum creatine phosphokinase (CPK), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) activities were assayed in 15 healthy but untrained subjects (US) and seven Olympic rowers (OR). Blood samples were obtained at rest, and five and 60 minutes after an ergometer test, during which cardiorespiratory data were obtained. OR demonstrated higher resting CPK (p < 0.001) and AST (p < 0.05) levels than the US. CPK and AST reached their highest levels five minutes after the end of the ergometer test in both groups, whilst peak ALT was reached five and 60 minutes post-test in the US and OR respectively. Fitness parameters and serum enzyme levels were better correlated in the OR group. It is concluded that: (1) exercise temporarily increases the activities of serum AST, ALT, and CPK, (2) increased physical fitness has no bearing on resting serum ALT enzyme levels, although this was not the case with AST and CPK, and (3) exercise duration rather than fitness levels seems to be related to serum CPK, AST, and ALT activities.

Adult↗
PubMed1992

U.K. multicentre study on blood donors for surrogate markers of non-A non-B hepatitis. Part I: Alanine transferase and anti-HBc testing.

Blood samples from 9,215 blood donors in three U.K. centres (North London, Bristol and Manchester) were tested for their alanine aminotransferase (ALT) level and the presence of anti-HBc and anti-HCV. This paper presents the results of the ALT and anti-HBc tests. The prevalence of ALT > 45 IU/l was 3.1% overall (North London 3.06%, Bristol 4.56% and Manchester 1.97%). Manchester results were skewed by the methodology used for ALT measurement, highlighting the need for standard test methods. Anti-HBc was detected using the Wellcome enzyme-immunosorbent assay (EIA) and confirmatory testing was performed using a radioimmunoassay (RIA) and the Corecell haemagglutination assay. Repeat reactive rates were 0.9, 0.79 and 0.94% for North London, Bristol and Manchester, respectively, with an overall rate of 0.9%. The confirmed positive rate was 0.73, 0.53 and 0.65% for the three centres with an overall rate of 0.63%. Donors with an ALT > 45 IU/l, or with confirmed anti-HBc, were interviewed with a medical questionnaire for risk factors. The major contributing factors in donors with a raised ALT were alcohol consumption and obesity.

Adolescent↗
PubMed1989

Medical and surgical management of spontaneous hyphaema secondary to immune thrombocytopenia.

The medical and surgical management of an unusual case of spontaneous 'black ball' hyphaema complicated by secondary haemorrhage, raised intraocular pressure and corneal blood staining, and secondary to immune thrombocytopenia is presented. The literature is reviewed with particular reference to the aetiology and treatment of spontaneous hyphaema and the role of intravenous immunoglobulins in the preoperative management of patients with thrombocytopenia who present for routine or emergency ocular surgery.

Female↗
PubMed1973

Further studies on the photosynthesis of carrot tissue cultures.

The influence of kinetin and sucrose on the photosynthetic activity of carrot (Daucus carota) tissue cultures in relation to growth was investigated. The results showed that light contributes heavily to the growth of tissue cultures measured in terms of fresh and dry weight and cell division activity. In light, the fresh weight, dry weight, and number of cells per explant were about or more than doubled. This indicated that after the development of chloroplasts, carrot tissue cultures can grow autotrophically at least as far as energy and carbon are concerned. Kinetin was shown to have an important role in developing the photosynthetic apparatus and photosynthetic activity of tissue cultures as manifested by the increase of chlorophyll content (60%), Hill activity (about 3-fold), and (14)C-fixation from NaH(14)CO(3) (about 20%). On the other hand, the presence of sucrose in the medium reduced the chlorophyll content by about 30% and (14)C-fixation from NaH(14)CO(3) in the soluble fraction by about 60%. A possible correlation between the influence of kinetin on sugar uptake and the effect of kinetin on (14)C-fixation from NaH(14)CO(3) was discussed.

Journal Article↗