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Biomedical subjects

A Rifai

Publications and source records attributed to A Rifai.

At least 37 records · Page 2Linked to original sources
PubMed1996

Increase of HLA-DR-positive natural killer cells in peripheral blood from patients with IgA nephropathy.

Previous in vivo and in vitro studies have presented various abnormalities of cellular immunity in patients with IgA nephropathy (IgAN). In the present study, we described increased expression of HLA-DR antigens on peripheral natural killer cells (NK cells) in relation to altered cytokine interactions. The numbers of HLA-DR expressing NK cells were enumerated by two-color flow cytometry and found to be significantly increased in patients with IgAN. Peripheral blood mononuclear cells were then fractionated into pure NK cells by a magnetic cell-sorting system and analyzed concerning expression of messages of interleukin (IL)-2, IL-4, tumor necrosis factor (TNF)-alpha, and interferon (IFN)-gamma by semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR). Among the four cytokines, only the IFN-gamma message was significantly increased in patients' NK cells. Furthermore, intensity of the IFN-gamma message in NK cells showed positive correlation with the percentage of HLA-DR-positive NK cells from the same patient. Then we assayed serum levels of IL-2, IL-12, and IFN-gamma by enzyme-linked immunosorbent assay (ELISA) and the levels of IL-12 and IFN-gamma showed positive correlations with HLA-DR expression on NK cells. Creatinine clearance of the patients was reevaluated 36 months later, and patients with high HLA-DR on NK cells tended to show faster deterioration of renal function than patients with lower HLA-Dr expression. On the basis of these findings, we suggested that HLA-DR-positive NK cells in patients with IgAN form an "activated" population that produces IFN-gamma, and this unique cell population may be maintained by multiple factors and be involved in the development and progression of IgAN.

Adult↗
PubMed1996

Clearance kinetics, biodistribution, and organ saturability of phosphorothioate oligodeoxynucleotides in mice.

We examined the dynamics of removal from circulation, tissue distribution, and persistence of phosphorothioate oligodeoxynucleotides (S-ODN) anti-tumor-necrosis-factor and a control of random sequence (randomer) in mice. After intravenous injection, the majority (96%) of S-ODN cleared rapidly from the circulation in the first two phases. In the first phase, 37.8 +/- 2.3% of the radioactivity had a mean half-life (t1/2) of 2.0 +/- 0.4 minutes. In the second phase, 58.1 +/- 1.5% of the radioactivity cleared with t1/2 of 12.6 +/- 0.2 minutes. The catabolic phase, constituting a minor proportion (4.1 +/- 0.8% of the total radioactivity), had a mean t1/2 of 2.7 +/- 0.5 hours. At a low dose (1 microgram) tissue distribution of both S-ODN anti-tumor-necrosis-factor and randomer were similar. The liver and kidneys were the major organs involved in uptake and removal of S-ODN. Autoradiographic studies showed the liver Kupffer cells to be the major site of uptake and renal urinary space for elimination. The clearance rate from the circulation was increased with the dose of S-ODN. In contrast, the fraction of radioactivity localized in the kidneys, liver, and spleen was decreased with increase in dosage. Furthermore, at a high dose (200 micrograms), the tissue distribution of the S-ODN anti-tumor-necrosis-factor differed significantly from the randomer. These findings have general significance in showing that the liver and kidneys are the major organs for removal of S-ODN and these organs are saturable at high doses. In addition, the results have specific importance in defining different parameters, dose and base composition, that affect utilization of antisense oligonucleotides for controlling gene expression in vivo.

Animals↗
PubMed1995

Hypertrophic osteoarthropathy caused by lipoid pneumonia.

A case of hypertrophic osteoarthropathy in a 5-year-old Saudi boy is presented. The child developed painful joints, was found to have clubbing of fingers and radiologically hypertrophic osteoarthropathy was demonstrated. The underlying cause of the condition was ingestion of animal fat in infancy, with a history of ghee oil aspiration which caused a chronic lung inflammation, lipoid pneumonia, proven by lung biopsy.

Child, Preschool↗
PubMed1995

Lack of production and growth-modulating effects of 1a,25-dihydroxyvitamin D3 in cultured fetal rat hepatocytes.

1a,25-Dihydroxyvitamin D3 [1,25(OH)2D3], the hormonal form of vitamin D3, has been shown to play a role in the regulation of growth of the regenerating adult rat liver following partial hepatectomy. In addition, a recent study implicated the neonatal liver as a possible extrarenal site of 1,25(OH)2D3 synthesis. Therefore, in our present study we used rapidly growing fetal hepatocytes in culture as a model cell line for regenerating hepatocytes and tested the hypothesis that fetal hepatocytes locally produce 1,25(OH)2D3 which in turn regulates their growth. Hepatocytes isolated from 19-day rat fetuses were grown in culture for 24 h in minimal essential medium without added serum or mitogens. To identify 1,25(OH)2D3 production, we incubated fetal hepatocytes in culture with 3H-25-hydroxyvitamin D3 (3H-25-OH D3) for 2, 6 and 24 h. High-pressure liquid chromatographic analysis of the lipid extract of the medium and cells revealed no evidence of conversion of 3H-25-OH D3 into 3H-1,25(OH)2D3. Additionally, to investigate the effect of 1,25(OH)2D3 on DNA synthesis in fetal liver, we measured 3H-thymidine incorporation by the cultured fetal hepatocytes following 24 h of exposure to various concentrations of 1,25(OH)2D3. The results of DNA synthesis revealed no effect of 1,25(OH)2D3 on fetal hepatocyte growth. As alterations in growth regulation by 1,25(OH)2D3 in other cells are thought to be mediated by intracellular vitamin D receptors (VDR), the expression of the VDR message in the fetal and maternal tissues of a pregnant rat was studied. RNA was first isolated from fetal liver, fetal kidney, maternal liver and maternal kidney, and the corresponding cDNA was then generated by reverse transcription.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Changes in tyrosine-phosphorylated p190 and its association with p120 type I and p100 type II rasGAPs during myelomonocytic differentiation of human leukemic cells.

A M(r) 190,000 protein (p190) functions as a GTPase-activating protein (GAP) for Rho and Rac family proteins, which are involved in regulating cytoskeletal actin and membrane ruffling. Tyrosine-phosphorylated p190 also complexes with rasGAP, a regulator of Ras activity, thus possibly linking Ras and Rho pathways. Leukemic cells induced to differentiate along myelomonocytic lineages have increased filamentous actin (as evidenced by phalloidin staining) and extended pseudopodia, and become irregularly shaped and flattened, suggesting altered Rho and Rac function. We, therefore, hypothesized that changes in p190 and its association with rasGAP are an integral part of these shape changes. During phorbol 13-myristate 25-acetate-induced monocytic differentiation of HL60 promyelocytic and RWLeu4 chronic myelogenous leukemic cells, the total amount of p190 decreases rapidly but returns to initial levels by 12 h. In RWLeu4, this was accompanied by commensurate changes in p190 tyrosine phosphorylation and association with p120 type I rasGAP. Association of p190 and type I rasGAP was demonstrated by immunoprecipitation with antibodies to either protein. An additional band at M(r) 100,000 (p100) was detected in immunoprecipitates after 12 h of phorbol 13-myristate 25-acetate treatment. Reverse transcription-PCR and immunoblot analyses suggest that p100 is type II rasGAP, an alternatively spliced product of p120 type I rasGAP. p100 was expressed only in response to direct protein kinase C activators, but all classes of differentiation agents increased tyrosine-phosphorylated p190. Rho and Rac are known to be involved in regulating actin polymerization. The results presented here show that the association of p190 with type I rasGAP parallels increases in actin polymerization and cell adhesion. This suggests a role for p190-rasGAP interactions in phorbol 13-myristate 25-acetate-induced cytoskeletal reorganization.

Base Sequence↗
PubMed1995

Evolution of renal injury in a chronic model of IgA immune-complex-associated nephropathy.

BACKGROUND: IgA nephropathy (IgAN) is characterized by intense and diffuse IgA mesangial deposits, a variety of histopathological changes and unpredictable clinical course. To elucidate the cause of the discrepancy between the unvariable IgA deposition and the histological picture, we examined the short- and long-term influence of glomerular IgA immune complexes (IgA-IC) on the progression of renal lesions in experimental IgAN. METHODS: IgA-IC renal deposits were induced by sequential administration of IgA antiphosphorylcholine and pneumococcal C polysaccharide. Mice treated every other day by three injections (groups A) or nine injections (groups B) were sacrificed 24 h and 1, 4, or 8 weeks (groups 1-4) after cessation of treatment. RESULTS: Group A1 showed segmental glomerular necrosis and thrombosis. Lesions then converted to segmental mesangial proliferation (A2), more pronounced in A3 and minimal in A4. Group B1 showed severe proliferative glomerulonephritis and segmental necrosis. The pattern altered to mesangial expansion with glomerular/interstitial infiltration in B2, milder features in B3 and residual mesangial proliferation in B4. Proteinuria increased progressively during treatment reaching its maximum in group B1, but it returned to near normal levels in group B4. The development of proteinuria paralleled glomerular/interstitial T cell infiltration. CONCLUSIONS: These findings demonstrate that renal histopathological alterations observed in experimental IgA nephropathy are sustainable only by continuous deposition of nephritogenic IgA-IC.

Animals↗
PubMed1994

Primary pelvic bone tumours in children and adolescents--imaging correlation.

Eight children aged 6 to 17 years (mean 13.3 years) were examined using conventional radiography, radionuclide bone scintigraphy, CT and MR imaging for pre-treatment assessment of extensive primary pelvic bone tumours. The tumours evaluated were Ewing's sarcoma (n = 4), osteogenic sarcoma (n = 3), and chondrosarcoma (n = 1). Each imaging modality made a contribution to the evaluation of the primary tumour. Conventional radiography and bone scintigraphy were necessary for the initial diagnosis, with CT playing a complementary role. MR imaging and/or dynamic contrast-enhanced CT were mandatory prior to surgical resection.

Adolescent↗
PubMed1993

Magnetic resonance imaging compared with angiography in the evaluation of intermediate-term result of coarctation balloon angioplasty.

Between July 1986 and December 1990, 24 consecutive adult patients with native coarctation of the aorta underwent balloon dilatation. Their ages ranged from 15 to 55 (mean 25) years. Dissection of the aorta developed in one patient. The remaining 23 patients were restudied by catheterization and magnetic resonance imaging (MRI) 8 to 60 (mean 21) months after dilatation. Both studies were performed between 1 and 180 (mean 40) days of each other. The diameter of the aorta at the site of previous coarctation was measured on angiogram and MRI by two independent observers. The data were compared by means of linear regression analysis. The gradient across the previous coarctation site ranged from 0 to 20 (mean 7 +/- 7.3) mm Hg. The diameter of the aorta at the site of previous coarctation measured on angiogram was 13.7 +/- 3.7 mm and on MRI it measured 13.5 +/- 3.7 mm, with excellent correlation (r = 0.96, SEE = 0.92, p < 0.001). Two patients had small aneurysms 2 cm in diameter demonstrated by angiography and MRI, and two patients developed restenosis, diagnosed correctly by both cardiac catheterization and MRI. This study demonstrates that MRI provides excellent visualization of the anatomy of the aorta and is a good noninvasive method for follow-up of patients undergoing balloon coarctation angioplasty.

Adolescent↗
PubMed1993

Placenta previa-percreta: magnetic resonance imaging findings and methotrexate therapy after hysterectomy.

A case is reported of a 42-year-old woman with placenta previa-percreta and multiple previous cesarean sections. Preoperative magnetic resonance imaging findings are described. Management included a cesarean supracervical hysterectomy, bilateral hypogastric arterial ligation, and intraoperative methotrexate administration. The placental portion that invaded the urinary bladder wall was left in place, without attempt to remove it surgically.

Adult↗
PubMed1993

Expression of 5-lipoxygenase and 5-lipoxygenase activation protein in glomerulonephritis.

The gene transcription of 5-lipoxygenase (5-LO) and 5-lipoxygenase-activating protein (FLAP) in renal tissue of patients with IgA nephropathy and mesangial proliferative glomerulonephritis were analyzed by amplification of reverse transcribed mRNA with polymerase chain reaction (PCR). The level of expression was determined by analysis of the PCR products of 5-LO, FLAP, and beta-actin. Forty percent of the patients expressed both 5-LO and FLAP. Relative to beta-actin, FLAP expression (0.42 +/- 0.21) was higher than 5-LO (0.14 +/- 0.10). Comparison of clinical data showed that patients who expressed 5-LO and FLAP had a lower glomerular filtration rate and an increased level of blood urea nitrogen, serum creatinine, and proteinuria. The results suggest arachidonic acid metabolism by inflammatory cells in renal tissue may play an important role in human glomerulonephritis.

5-Lipoxygenase-Activating Proteins↗
PubMed1992

Extrarenal cytokines modulate the glomerular response to IgA immune complexes.

Clinical episodes of IgA nephropathy coincide recurrently with microbial infections. Cytokines produced during such infections may play a role in the pathogenesis of IgA-associated glomerulonephritis. To test this hypothesis, we examined the influence of passively administered proinflammatory cytokines (IL-1, IFN-gamma and IL-6) on the development of glomerulonephritis in an experimental model of IgA nephropathy. Glomerular IgA immune deposits were induced in mice by administration of IgA anti-phosphorylcholine (PC) with either a PC-containing carbohydrate antigen of Pneumococcal C polysaccharide (PnC) or a protein antigen of PC-conjugated bovine serum albumin (PC-BSA). The effect of IL-1 on the IgA-PC-BSA induced glomerular changes resulted in an increase of mesangial hypercellularity that was associated with mild proteinuria and hematuria. Mice treated with IL-1 and IgA-PnC developed diffuse proliferative glomerulonephritis with proteinuria and hematuria. In contrast, IL-6 treatment with IgA-PC-BSA of IgA-PnC failed to exert any significant renal effect. The combination of IL-6 and IL-1, however, intensified the mesangial hypercellularity of the IgA-PC-BSA, and induced severe proliferative glomerulonephritis with inflammatory monocytes and neutrophils infiltrates in the IgA-PnC treated mice. These glomerular changes were also accompanied by increased proteinuria and hematuria. Similarly, the combination of IFN with IL-1 produced histologic changes and compromised renal function more than IFN or IL-1 exerted independently. These results suggest that extrarenal cytokines influence the renal response to IgA immune deposits. We also conclude that a synergy of multiple cytokines and nephritogenic antigens immobilized in glomerular IgA immune deposits may lead to rapid progression of IgA-associated glomerulonephritis.

Animals↗
PubMed1992

Conjoined twins: medical, surgical and ethical challenges.

Four sets of conjoined twins were reviewed. One set was of the omphalopagus type with no associated abnormalities and were successfully separated at 12 days of age. The other three were of the thoracoomphalopagus type with major cardiac and other abnormalities, they were not amenable to surgery and did not survive. Conjoined twins require precise clinical and radiological evaluation. Many factors contribute to the management of such twins and ethical issues must be considered before surgical separation is undertaken.

Abnormalities, Multiple↗