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A Rifai

Publications and source records attributed to A Rifai.

At least 19 recordsLinked to original sources
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↗
PubMed1991

Antigen as mediator of glomerular injury in experimental IgA nephropathy.

IgA immune complexes (IgA-IC) are considered the primary cause of IgA nephropathy. Despite the consistent findings of IgA and frequently C3 glomerular deposits in most patients, the renal histopathologic lesion may vary from mild mesangial involvement to severe sclerosis. In the IgA immune deposits, IgA and C3 are considered to be relatively constant, whereas the composition of the antigen is expected to vary according to its origin. This report explored th possibility that the histopathologic lesion is a function of the antigen in an IgA immune deposit. To test this hypothesis we developed a passive model of IgA nephropathy whereby glomerular IgA deposits can capture, in situ, circulating antigens. In this model, glomerular IgA deposits (IgA/IgA-IC) were induced by administration of a constant amount of IgA anti-dinitrophenyl (antibody) and dinitrophenyl-conjugated IgA anti-phosphorylcholine (PC) as an antigen. The latter also served as antibody to capture, in situ, circulating PC-containing antigens. Mice that received only IgA/IgA-IC developed glomerular IgA and C3 deposits and a focal increase in mesangial cells and matrix, but no evidence of renal damage. A diffuse increase in mesangial cells and matrix developed in mice treated with IgA/IgA-IC and either PC-Ficoll (carbohydrate antigen) or PC conjugate of bovine serum albumin (protein antigen). In contrast, mice that received IgA/IgA-IC and pneumococcal C polysaccharide, a PC-containing antigen, developed severe diffuse mesangial hypercellularity with segmental necrosis and thrombosis. These mice also developed proteinuria and hematuria. Our results demonstrate that the antigen plays a critical role in development of glomerulonephritis associated with IgA-IC.

Animals↗
PubMed1990

The use of Gd-DOTA in magnetic resonance imaging of experimentally induced mammary tumors.

Gd-DOTA contrast enhancement of MR images was evaluated on induced mammary tumors in female rats. A single intravenous injection of the carcinogenic N-nitrosourea ENU was administered to Wistar rats; this simple treatment led to a high percentage of mammary tumors without causing death. All the induced tumors were adenocarcinoma and their heterogeneousness depended on their size. The induced tumors did not have intra- or extravascular inflammatory spaces caused by heterotopic lesions, as is the case with implanted tumors. Before injection of Gd-DOTA, appearance of the patchy internal structure was clearly demonstrated on spin-echo images performed with long repetition times. Three doses of the paramagnetic contrast agent (0.1, 0.2, and 0.5 mmol/kg) were evaluated on two different T1-weighted MR sequences. Images were recorded before and repeatedly after intravenous injection of Gd-DOTA, and signal intensities and relaxation times were measured. On images acquired with the spin-echo 500/28 as well as the inversion-recovery 928/26/300 sequences, the results showed that 0.2 mmol/kg Gd-DOTA was the optimal dose for contrast enhancement and for clear visualization of the heterogeneousness of the mammary tumor.

Adenocarcinoma↗
PubMed1990

Magnetic resonance imaging of thoracic hydatid disease. Correlation with clinical findings, radiography, ultrasonography, CT and pathology.

Two patients with thoracic manifestations of hydatid disease (HD) are discussed; one patient had recurrent HD of the chest wall and the other, intrapulmonary HD after rupture and intrathoracic extension of an infradiaphragmatic cyst. At magnetic resonance (MR) imaging the manifestations of HD in the thorax are similar to previously reported MR findings in HD in the liver. The presence of a low signal intensity rim on T2 weighted images representing the cyst wall was confirmed. On T1 weighted images cysts with heterogeneous low and intermediate signal intensity contents and a relatively high signal intensity wall were seen. 'Folded parasitic membranes' previously not described on MR were noted. Daughter cysts may have a low or high signal intensity depending on contents. Reactive changes in the lung may be quite marked compared with the liver, due to reaction to the parasite or simply because the lung is more easily compressed leading to secondary atelectasis.

Adult↗
PubMed1990

Clearance kinetics, tissue localization and fate of IgA-anti-idiotype complexes.

To determine the influence of anti-idiotypic antibodies on the complementary idiotype (Id), the clearance kinetics, tissue distribution and fate of idiotype-anti-idiotype complexes were investigated in mice. The complexes were prepared by mixing purified radiolabelled monomeric (mIgA) or polymeric IgA (pIgA) with monoclonal anti-T15 idiotype (B39-38). The 24 hr clearance from circulation of intravenously administered mIgA, mIgA-anti-Id complexes, pIgA and pIgA-anti-Id complexes showed three exponential phases. There was no significant difference in the amount, half-life (t 1/2), or organ distribution of mIgA and mIgA-anti-Id during the first two phases. The mIgA-anti-Id complexes were removed at a faster rate (9.2 +/- 0.5 hr) than the mIgA alone (17.7 +/- 1.3 hr) during the third phase. In contrast, anti-Id affected the clearance of pIgA during the first phase whereby 75% of the administered pIgA-anti-Id complexes, compared with 50% of the pIgA, cleared from the circulation with a t 1/2 of 3 min. This rapid removal from circulation was mediated predominantly by the liver, where 66% of pIgA-anti-Id and 40% of pIgA were detected 10 min after administration of the radiolabelled material. In the second phase, pIgA-anti-Id were removed from circulation at a faster rate (t 1/2 = 28 min) than pIgA (t 1/2 = 43 min). During this phase, 1 hr after administration of radiolabelled material, significantly more pIgA-anti-Id than pIgA were localized in the liver, kidneys, skin and spleen. In contrast, the digestive tract contained more pIgA (22%) than pIgA-anti-Id (11%). Analysis of the mIgA-anti-Id and pIgA-anti-Id by gradient polyacrylamide gel electrophoresis indicated that mIgA-anti-Id were composed of small-sized complexes, while intermediate-sized complexes constituted the majority of the pIgA-anti-Id complexes. These results suggest that the modulatory effect of anti-Id on the complementary IgA idiotype is determined largely by the molecular form of the IgA and the size of the Id-anti-Id complexes.

Animals↗
PubMed1989

Classical pituitary apoplexy presentation and a follow-up of 13 patients.

Thirteen patients who presented with signs and symptoms of pituitary disease gave a history of classical pituitary apoplexy. Six presented with acute symptoms and in 7 the history antedated the admission by a mean of 887 days (range 365-2,190 days). All patients had an enlarged eroded sella. CT scans revealed a bleed in the tumor in 11 (histologically confirmed in all 8 patients operated), evidence of residual tumor in 1 and an empty sella (ES) in 1 patient. Hypopituitarism was present in 9, 4 were endocrinologically normal, 8 had visual problems requiring decompressive surgery and radiotherapy (RT) was given to 7 patients. They were subsequently followed for a median period of 730 days (range 365-3,385 days). During this time an empty sella developed in 5, 2 of whom had no surgery or RT; 4 remained endocrinologically normal, and a second hemorrhage occurred in 2 patients. Histological evidence of previous bleeds was noted in 6 of the 8 patients treated surgically. We conclude that apoplexy (1) may produce complete or partial tumor destruction with or without preservation of endocrine function; (2) recurrent, often silent, bleeding into a pituitary tumor appears to be a common event; (3) RT should be withheld unless recurrent tumor is documented (since at least 2 patients in this study have experienced spontaneous resolution of the tumor); and (4) the presence of an enlarged eroded fossa with an ES is reasonable presumptive evidence of an infarction of a pre-existing pituitary tumor.

Adult↗
PubMed1989

Clearance kinetics and fate of macromolecular IgA in patients with IgA nephropathy.

IgA glomerulonephritis is associated with macromolecules of polymeric IgA in the circulation and mesangial deposits. An impairment in the reticulophagocytic function of patients with IgA nephropathy has been postulated as the potential cause for persistence of IgA immune complexes in the circulation and their eventual glomerular deposition. Since the fate and removal mechanisms of circulating macromolecular IgA are unknown in humans, we examined the blood clearance and organ uptake of purified IgA polymers and macromolecules in patients with IgA nephropathy and normal controls. The IgA macromolecules were prepared by covalent cross-linking of purified human polymeric IgA with a heterobifunctional reagent, N-succinimidyl 3-(2-pyridyldithio) propionate. After intravenous injection, large IgA molecules were removed rapidly from the circulation of patients (t1/2 = 3.8 +/- 1.0 minutes) and controls (t1/2 = 4.9 +/- 1.5 minutes). Dynamic gamma camera scintigraphy revealed the liver as the major organ that mediated the removal of the macromolecular IgA with no significant difference in the rate of hepatic uptake for patients (t1/2 = 3.4 +/- 0.6 minutes) and controls (t1/2 = 3.3 +/- 0.9 minutes). No significant amount of radioactivity could be detected in the lungs, kidneys, and spleen. The small polymers had a slower and similar clearance rates for patients (t1/2 = 29.3 +/- 7.9 h) and controls (t1/2 = 29.0 +/- 8.6 h). These findings have general significance in showing the liver as a major organ for removal of macromolecular IgA. In addition, the results have specific importance in showing that patients with IgA nephropathy do not suffer from an IgA removal dysfunction.

Adolescent↗
PubMed1988

IgA nephropathy, the most common glomerulonephritis worldwide. A neglected disease in the United States?

Although its prevalence and clinical importance in the United States are stated to be low, we believe IgA nephropathy occurs as commonly in this country as in Western Europe. Initial reports suggested the disease was perhaps restricted to France and synonymous with "benign recurrent hematuria," but longer follow-up has proven both conclusions incorrect. Obviously, major gaps persist in our understanding of the immunopathogenesis and the natural history. The latency of the American investigative response calls for more intensive clinical and laboratory studies of the most common primary glomerulonephritis worldwide.

Antigen-Antibody Complex↗
PubMed1988

Characteristics of nephritogenic IgA immune complexes.

Studies were undertaken to elucidate the characteristics of IgA immune complexes responsible for glomerular deposition and complement activation. Monomeric IgA antidinitrophenyl (DNP) and the antigen DNP-Ficoll tended to form small soluble complexes that circulated in the blood without localizing in glomeruli of experimental animals. In contrast, polymeric IgA formed intermediate and large-sized complexes that caused glomerular immune deposits. Although covalently cross-linked large-sized IgA oligomers deposited in the glomeruli, they failed to induce concomitant deposition of complement components. Only the presence of a complement-activating antigen endowed the glomerular IgA immune deposits with the ability to activate complement. Thus, the size of the IgA complexes plays a primary role in initiating glomerular localization, and the nature of the antigen causes a secondary phase of inflammation.

Animals↗
PubMed1988

Hepatic binding of DNA is mediated by a receptor on nonparenchymal cells.

During cell death, nuclear material is released into the cellular environment and into the circulation. Studies in experimental animals have shown that circulating DNA is rapidly removed by the liver and broken down to oligonucleotides. The authors have used a perfused liver system in the mouse to study hepatic binding of single-stranded DNA. DNA binding to the liver was rapid and efficient, and did not require serum factors. Binding was saturable and temperature independent, suggesting a receptor-mediated process. Electron microscope autoradiography demonstrated DNA binding to sinusoidal lining cells, primarily Kupffer cells. In vitro studies with isolated cells confirmed that DNA bound to a trypsin-sensitive receptor on the adherent subset of hepatic nonparenchymal cells. The integrity of the perfused liver was confirmed by the demonstration of appropriate uptake and breakdown of asialoorosomucoid. Despite rapid binding of DNA, however, the perfused liver did not digest DNA or release DNA breakdown products. Infusion of DNAse at intervals after DNA perfusion demonstrated that significant amounts of DNA remained bound to the cell surface, and that serum nucleases were able to cleave this surface bound DNA. It is concluded that DNA binding to the liver is mediated by a receptor on Kupffer cells, but that DNA breakdown may occur at the cell surface or in circulation and may not require cell interiorization.

Animals↗
PubMed1988

Lack of complement activation by human IgA immune complexes.

Complement activation may play an important role in renal injury associated with glomerular deposition of IgA immune complexes. The ability of naturally occurring human IgA immune complexes (IgA-IC) and covalently cross-linked human IgA oligomers (X-IgA) to activate complement were examined in vitro and in vivo. Large-sized IgA-IC were isolated from a patient's serum by affinity purification (Jacalin-Sepharose) and gel chromatography. Stable X-IgA were prepared by chemical cross-linking with a heterobifunctional reagent, N-succinimdyl 3-(2-pyridyl-dithio) propionate (SPDP). Treatment of fresh normal human serum with large amounts of either IgA-IC or X-IgA failed to activate C3. The C3 consumption was measured immunochemically by the decrease of the B antigen on the native C3 and by the generation of iC3b. Addition of these complexes to serum did not result in cleavage of factor B. Administration of human IgA-IC or X-IgA to mice, killed after 6 h, resulted in glomerular deposition of IgA. Despite the presence of intense glomerular IgA deposits no C3 was detected. Collectively, these findings suggest that neither soluble nor renal localized human IgA complexes activate complement.

Animals↗
PubMed1988

Glomerular immune deposits in experimental IgA nephropathy. A continuum of circulating and in situ formed immune complexes.

Studies were undertaken to elucidate the primary pathogenetic mechanisms responsible for immunoglobulin (Ig) A immune complexes formation and glomerular deposition in vivo. Monomeric (mIgA) and polymeric IgA (pIgA) anti-dinitrophenyl (DNP) were purified from MOPC 315 myeloma. A DNP-conjugated Ficoll was used as an antigen. For simulation of natural conditions of in vivo immune complex formation, 131I-DNP-Ficoll and 125I-IgA were administered through the intravenous and intraperitoneal routes, respectively. The kinetics half-life (t1/2) of the antigen (2.9 hours) and either the pIgA (7.2 hours) or mIgA (6.3 hours) in the experimental groups was not significantly different from the control. Glomerular IgA immune deposits were detectable only in mice that received pIgA and DNP-Ficoll. Plasma samples analyzed by gradient polyacrylamide gel electrophoresis revealed formation of large- and intermediate-sized pIgA complexes in circulation prior to glomerular deposition. Although mIgA failed to interact with such complexes in the circulation, it did bind to the pIgA immune deposits in the glomerulus. These results indicate that glomerular IgA immune deposits evolve from the localization of preformed circulating pIgA complexes that eventuates an in situ mIgA-mediated complex formation.

Animals↗
PubMed1987

Composition of IgA immune complexes precipitated with polyethylene glycol. A model for isolation and analysis of immune complexes.

Covalently cross-linked large and intermediate-sized IgA oligomers, prepared with IgA anti-dinitrophenyl (DNP) and bis-DNP-pimelic acid ester, were used to examine the ability of different concentrations (3.5%, 5% and 7%, w/v) of polyethylene glycol (PEG) to precipitate IgA immune complexes (IgA-IC). The size of the IgA-IC precipitated with PEG was determined by gradient polyacrylamide gel electrophoresis and quantitative autoradiography. The standard concentration of 3.5% PEG precipitated only a minor fraction (20%) of the IgA-IC. In contrast, 5% and 7% PEG precipitated 45% and 79% of the complexes, respectively. To test the influence of the antigen on the PEG assay. IgA-IC prepared with IgA anti-DNP and DNP conjugates of either bovine serum albumin or Ficoll were also used. Approximately 38% of these IgA-IC were precipitated with 3.5%, PEG. By comparison, the concentration of 5% and 7% PEG precipitated 60% and 76% of the IgA-IC, respectively. Distilled water rather than the standard borate-buffered saline was shown to be the optimal solvent for resolubilization of the PEG precipitates. Serum samples from 22 IgA nephropathy patients and 12 normal donors were tested with 3.5%, 5% and 7% PEG. Only the 7% PEG assay showed a significant difference between patients and controls (P less than 0.001) in the IgA levels of precipitates. Thus, the use of 7% PEG is recommended for the detection, isolation and analysis of large- and intermediate-sized IgA-IC.

Antigen-Antibody Complex↗
PubMed1987

A combined infratemporal and posterior fossa approach for the removal of giant glomus tumors and chondrosarcomas.

Giant glomus jugulare tumors with a large posterior fossa extension are considered either inoperable or at least requiring of a two-stage operation. Likewise, the surgical approach and treatment for chondrosarcomas of the temporal bone are controversial. We describe a combined approach in which, with the aid of microsurgical and laser techniques, such tumors can be removed in one stage. The surgical approach involves a lateral infratemporal approach combined with a posterior fossa craniectomy. This technique was used in seven cases: five glomus jugulare tumors and two chondrosarcomas. There were no deaths, and surgical morbidity consisted of weakness in the facial nerve in four of these patients and gastrointestinal hemorrhage and respiratory distress syndrome in one patient.

Brain Neoplasms↗
PubMed1987

Complement activation in experimental IgA nephropathy: an antigen-mediated process.

Complement activation associated with immune complex glomerular deposition plays an important role in renal injury. In the present studies we performed three series of experiments to identify how IgA immune complexes activate complement. The first series of experiments was designed to determine whether the presence of an antigen within a glomerular IgA immune deposit is required for complement activation. In these experiments, large-sized covalently cross-linked IgA oligomers (X-IgA) were prepared with purified IgA anti-dinitrophenyl (DNP) and a bivalent affinity-labeling antigen, bis-2,4-DNP-pimelic acid ester. These X-IgA oligomers have free antigen-binding sites that will bind DNP-conjugated antigens. Two groups of mice were treated with either X-IgA or X-IgA followed, after two hours, by an antigen DNP-Ficoll. Immunofluorescent examination of renal tissues, obtained six hours after the initial injection, revealed an equal intensity of IgA glomerular deposits in both groups of mice. Glomerular C3 deposits were only detectable in the renal tissues of mice that had DNP-Ficoll bound to X-IgA. In the second series of experiments, a pair of preformed IgA immune complexes, differing only in one antigenic structural feature (DNP), were used to examine the role of the antigen in inducing glomerular C3 deposits in two groups of mice. These pre-formed immune complexes were prepared with IgA anti-phosphorylcholine (PC) and either PC-conjugated to bovine serum albumin (PC-BSA) or PC-BSA which was further modified with DNP (PC/DNP-BSA). Although the IgA immunofluorescent intensity and pattern in the glomerular deposits were equivalent for both groups, intense C3 deposits were exclusively associated with the PC/DNP-BSA-containing immune complexes. Analysis of the relative conversion of normal human serum C3 to inactive C3b (iC3b) by X-IgA, various antigens and their respective IgA immune complexes was highly dependent on the nature of the antigen.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗