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A Rifai

Publications and source records attributed to A Rifai.

At least 19 recordsLinked to original sources

Profiling the adult human liver transcriptome: analysis by cDNA array hybridization.

BACKGROUND/AIMS: A comprehensive profile of genes expressed at the mRNA level (transcriptome) in human liver tissue is important for elucidating the pathogenesis and treatment of hepatic diseases. The recent development of cDNA array hybridization allows the parallel monitoring of thousands of genes expressed in a single organ. METHODS: High-density microarrays containing 4043 known and unique human cDNA gene targets were used to quantitatively analyze the expression of genes in human livers. Expressed gene transcripts were classified by function and listed with information of their chromosomal positions. Computational analysis was used to cluster genes according to similarity in pattern of gene expression. RESULTS: A total of 2418 unique gene transcripts were detected in five liver specimens. Through relational database analysis, we determined 1212 genes that were commonly expressed in 4 of the five liver specimens. Furthermore, analysis of the total 2418 expressed genes by self-organizing maps and hierarchical clustering unexpectedly revealed a genomic acute phase response in two of the liver specimens. CONCLUSIONS: These findings represent a comprehensive preliminary molecular index of genes transcribed in the adult human liver. The information may serve as a resource for speeding up the discovery of genes underlying human hepatic diseases.

Adult↗

Atraumatic osteonecrosis of the patella.

Atraumatic secondary osteonecrosis of the patella is a rare entity and has been reported in only several case reports. The purpose of this study was to define the clinical and radiographic characteristics and outcome of this disease. Osteonecrosis of the patella was found in 25 knees in 19 patients. The mean age was 42 years (range, 21-63 years). Eighteen (95%) patients had greater than 2 g of lifetime corticosteroid exposure, and six (32%) patients had systemic lupus erythematosus. Osteonecrosis was found in the superior pole of the patella in all 23 knees (17 patients) that had magnetic resonance imaging. Osteonecrosis was apparent on plain radiographs in five knees (20%) in four patients, and only one knee (4%) in one patient had collapse of the posterior articulating surface of the patella. One (4%) patient presented with anterior knee pain localized to the patella. At a mean followup of 4 years (range, 2-18 years), none of the patients had an intervention that focused on treating the patellar lesion. Patellar osteonecrosis is characterized by patients with coincident lesions of the distal femur and the proximal tibia and lesions localized to the superior pole of the patella. It is a nonprogressive disease that does not warrant surgical exploration.

Adult↗

Genomic approaches to elucidating the pathophysiology of renal diseases.

The physiological and pathological processes of the kidney as a whole can now be analyzed with a molecular precision at a genomic-scale. Using massively parallel cDNA microarray technology, the mRNA expression of thousands of genes can be quantified simultaneously. The advantages of microarray analyses include the ability to examine the interaction of several genes or the entire genome in a single experiment. Bioinformatics approaches such as data mining through mathematical condensation of the massive gene expression profiles are essential for elucidating molecular and biological logic underlying gene expression programs. Genes that encode similar protein components are often coordinately regulated. Recent application of gene expression profiling to the normal human renal cortical tissue, experimental in vitro and in vivo models has shown that cellular activation is accompanied by changes of hundreds of genes in parallel. The databases of gene expression emerging from these studies will be used to interpret the pathological changes in gene expression that accompany a variety of human renal diseases.

Gene Expression Profiling↗

The N-glycans determine the differential blood clearance and hepatic uptake of human immunoglobulin (Ig)A1 and IgA2 isotypes.

Human immunoglobulin (Ig)A exists in blood as two isotypes, IgA1 and IgA2, with IgA2 present as three allotypes: IgA2m(1), IgA2m(2), and IgA2m(n). We now demonstrate that recombinant, chimeric IgA1 and IgA2 differ in their pharmacokinetic properties. The major pathway for the clearance of all IgA2 allotypes is the liver. Liver-mediated uptake is through the asialoglycoprotein receptor (ASGR), since clearance can be blocked by injection of excess galactose-Ficoll ligand and suppressed in ASGR-deficient mice. In contrast, only a small percentage of IgA1 is cleared through this pathway. The clearance of IgA1 lacking the hinge region with its associated O-linked carbohydrate was more rapid than that of wild-type IgA1. IgA1 and IgA2 that are not rapidly eliminated by the ASGR are both removed through an undefined ASGR-independent pathway with half-lives of 14 and 10 h, respectively. The rapid clearance of IgA2 but not IgA1 through the liver may in part explain why the serum levels of IgA1 are greater than those of IgA2. In addition, dysfunction of the ASGR or altered N-linked glycosylation, but not O-glycans, that affects recognition by this receptor may account for the elevated serum IgA seen in liver disease and IgA nephropathy.

Animals↗

Comprehensive gene expression profile of the adult human renal cortex: analysis by cDNA array hybridization.

BACKGROUND: Profiling of gene expression in healthy and diseased renal tissue is important for elucidating the pathogenesis of renal diseases. Comprehensive information about the genes expressed in renal tissue is unavailable. The recently developed cDNA array hybridization methodology allows simultaneous monitoring of thousands of genes expressed renal tissue. METHODS: Complex [alpha-33P]-labeled cDNA probes were prepared from histopathologically uninvolved remnants of nine renal tissues obtained by nephrectomy. Each probe was hybridized to a high-density array of 18,326 paired target genes. The radioactive hybridization signals by phosphorimager screens were quantitated by special software. Bioinformatics from public genomic databases were used to assign a chromosomal location of each expressed transcript and gene function. Cluster analysis was used to arrange genes according to the similarity in pattern of gene expression. RESULTS: A total of 7563 different gene transcripts was detected in the nine tissue samples. Approximately 870 of these genes were full-length mRNA human transcripts (HT), and the remaining 6693 were expressed sequence tags (ESTs). The full-length transcripts were classified by function of the gene product and were listed with information of their chromosomal positions. To allow a comparison between gene expression in clinical and experimental studies, the mouse genes with known similar function to the human counterpart were included in the bioinformatics analysis. Cluster analysis of 502 full-length genes that are expressed in four or more renal tissues revealed more than 110 genes that are highly expressed in all the renal specimens. CONCLUSIONS: The presented data constitute a comprehensive preliminary transcriptional map of the adult human renal cortex. The information may serve as a resource for speeding up the discovery of genes underlying human renal disease. The integrated listing of the full-length expressed human and mouse genes is available through e-mail (Abdalla_Rifai@Brown.edu).

Adult↗

Atraumatic osteonecrosis of the knee.

BACKGROUND: The purposes of this study were to define the clinical, demographic, and radiographic patterns of atraumatic osteonecrosis of the distal part of the femur and the proximal part of the tibia at presentation and to report the outcome of treatment of this condition. METHODS: Two hundred and forty-eight knees in 136 patients who were younger than the age of fifty-five years were treated at our institution between July 1, 1974, and September 15, 1998, for atraumatic osteonecrosis of the distal part of the femur or the proximal part of the tibia, or both. Demographic and radiographic features were characterized. The results of nonoperative treatment, core decompression, arthroscopic debridement, and total knee arthroplasty were evaluated. RESULTS: There were 106 female patients and thirty male patients, and their mean age was thirty-six years (range, fifteen to fifty-four years) at the time of diagnosis. One hundred and one patients (74 percent) had involvement of other large joints, with eighteen (13 percent) presenting initially with knee symptoms. One hundred and one patients (74 percent) had a disease that affected the immune system; sixty-seven of them had systemic lupus erythematosus. One hundred and twenty-three patients (90 percent) had a history of corticosteroid use. Technetium-99m bone-scanning missed lesions in sixteen (29 percent) of fifty-six knees. Eight (20 percent) of forty-one initially symptomatic knees treated nonoperatively had a successful clinical outcome (a Knee Society score of at least 80 points and no additional surgery) at a mean of eight years. The knees that remained severely symptomatic for three months were treated with either core decompression (ninety-one knees) or total knee arthroplasty (seven knees). Seventy-two (79 percent) of the ninety-one knees treated with core decompression had a good or excellent clinical outcome at a mean of seven years. Efforts to avoid total knee arthroplasty with repeat core decompression or arthroscopic debridement led to a successful outcome in fifteen (60 percent) of twenty-five knees. Thirty-four (71 percent) of forty-eight knees treated with total knee arthroplasty had a successful clinical outcome at a mean of nine years. CONCLUSIONS: Atraumatic osteonecrosis of the knee predominantly affects women, and in our study it was associated with corticosteroid use in 90 percent of the patients. Evaluation should include standard radiographic and magnetic resonance imaging of all symptomatic joints. Prognosis was negatively related to large juxta-articular lesions. Nonoperative treatment should be reserved for asymptomatic knees only. Core decompression was successful (a Knee Society score of at least 80 points and no additional surgery) in 79 percent of the knees in which the disease was in an early stage. Total knee arthroplasty was successful in only 71 percent of the knees.

Adolescent↗

Gene expression of 5-lipoxygenase and LTA4 hydrolase in renal tissue of nephrotic syndrome patients.

Leukotrienes (LT) of the 5-lipoxygenase pathway constitute a class of potent biological lipid mediators of inflammation implicated in the pathogenesis of different models of experimental glomerulonephritis. The key enzyme, 5-lipoxygenase (5-LO), catalyses oxygenation of arachidonic acid to generate the primary leukotriene LTA4. This LT, in turn, serves as a substrate for either LTA4 hydrolase, to form the potent chemoattractant LTB4, or LTC4 synthase, to produce the powerful vasoconstrictor LTC4. To investigate the potential role of LT in the pathogenesis of human glomerulonephritis with nephrotic syndrome, we examined the gene expression of 5-LO and LTA4 hydrolase in renal tissue of 21 adult patients with nephrotic syndrome and 11 controls. The patients consisted of 11 cases of membranous nephropathy (MN), seven focal and segmental glomerulosclerosis (FSGS), two non-IgA mesangial glomerulonephritis and one minimal change disease. Total RNA purified from renal tissue was reverse transcribed into cDNA and amplified with specific primers in a polymerase chain reaction (RT-PCR). Eight patients' renal tissue, four MN and four FSGS, co-expressed 5-LO and LTA4 hydrolase. In situ hybridization analysis revealed 5-LO expression and distribution limited to the interstitial cells surrounding the peritubular capillaries. Comparative clinical and immunohistological data showed that these eight patients had impaired renal function and interstitial changes that significantly correlated with 5-LO expression. These findings suggest that leukotrienes may play an important role in the pathogenesis of MN and FSGS. These results are also relevant to elucidating the pathophysiologic mechanisms which underlie progression to renal failure in these diseases.

Adult↗

Imaging of abdominal neuroblastoma in children.

PURPOSE: The aims of the study were: 1) to assess the efficacy of different imaging methods for use prior to treatment; 2) to compare the surgico-histopathologically-based International Neuroblastoma Staging System (INSS) staging with the imaging results; and 3) to suggest a localisation scheme for abdominal neuroblastoma. MATERIAL AND METHODS: Thirty-one children with an abdominal neuroblastoma (median age 2 years), underwent abdominal US, CT of chest and abdomen, MR imaging of abdomen and spine, chest radiography, skeletal survey, radionuclide bone scintigraphy, MIBG scintigraphy, and bone marrow biopsy. RESULTS: In the evaluation of local disease, CT and MR were superior to US. There was no significant difference between CT and MR in assessment of the location or size of the tumour. Evaluation of invasive growth and lymphadenopathy was uncertain irrespective of imaging modality. Intraspinal extension was more distinctly demonstrated with MR. Tissue characterization with CT and MR did not contribute in the assessment of the tumours. Contrast enhancement at CT and MR examinations both improved demarcation between tumour and kidney, and was a necessity for evaluation of vessel encasement with CT. The local disease was best assessed by either CT or MR, while metastatic disease was best revealed by CT, MR, scintigraphy or bone marrow biopsy. CONCLUSION: Imaging may be a valuable basis for clinical assessment and pretreatment staging of abdominal neuroblastoma.

3-Iodobenzylguanidine↗

An unusual cause of obstructive sleep apnoea presenting during pregnancy.

We describe a case of lingual thyroid (LT) with primary hypothyroidism, presenting during pregnancy and continuing beyond it with oropharyngeal obstructive symptoms and sleep apnoea syndrome (SAS) of mixed type. Although SAS of a combined obstructive and central type should not be too surprising in a case of LT with hypothyroidism, we were unable to find such a documentation previously. Only four weeks of L-thyroxin treatment resulted in a dramatic improvement in dysphagia, disturbed phonation, haemoptysis, arterial desaturation, sleep apnoea and overall sleep efficiency, in conjunction with a regression in the size of the lingual mass. This case highlights the vagaries confronted in the management of such a case and focuses on efforts towards accurate diagnosis and treatment.

Adult↗

Sphenoid sinus brown tumor of secondary hyperparathyroidism: case report.

OBJECTIVE AND IMPORTANCE: Brown tumor is a misnomer for a reparative cellular process caused by primary or, less commonly, secondary or tertiary hyperparathyroidism. Atypical involvement of the base of the cranium in the area of the sphenoid sinus and the orbit is exceedingly rare and may produce a neurological deficit as a primary clinical presentation. Those neurosurgeons dealing with cranial base and pituitary lesions should be aware of this disease entity, and it should be listed in the differential diagnosis. CLINICAL PRESENTATION: A 21-year-old woman with end-stage renal failure on chronic dialysis was referred to the Department of Neurosciences at King Faisal Specialist Hospital and Research Centre with a 4-month history of progressive impairment of vision, associated with headache and nausea. Computed tomography and magnetic resonance imaging demonstrated an expansive mass lesion in the sphenoid sinus with erosion of the sellar floor and posterior medial wall of the orbit causing compression of the optic nerves. The biochemical laboratory studies showed elevation of parathyroid hormone and confirmed the diagnosis of hyperparathyroidism. INTERVENTION: The transnasal-transsphenoidal approach was used for extensive microsurgical removal of the lesion. The postoperative course was uneventful, and the improvement in vision was dramatic. CONCLUSION: Brown tumor, although rare, should be listed in the differential diagnosis of expansive mass lesions in the area of the sphenoid sinus and cranial base. The management is multidisciplinary, and therapeutic options should target the underlying cause.

Adult↗

One- to ten-year follow-up results of balloon angioplasty of native coarctation of the aorta in adolescents and adults.

OBJECTIVES: We attempted to evaluate the role of balloon angioplasty in the treatment of discrete coarctation of the aorta in adolescents and adults, with special emphasis on long-term results. BACKGROUND: Controversy persists over the use of balloon dilation for the treatment of native coarctation of the aorta. METHODS: Between July 1986 and January 1997, 43 consecutive adolescent and adult patients with discrete coarctation of the aorta underwent balloon angioplasty. One- to 10-year follow-up data of 37 patients, including results of cardiac catheterization and magnetic resonance imaging (MRI), form the basis of this study. RESULTS: No early or late deaths occurred. Balloon angioplasty produced a reduction in the peak to peak coarctation gradient from a mean +/- SD of 69 +/- 24 mm Hg (95% confidence interval [CI] 61 to 76) to 12 +/- 8 mm Hg (95% CI 10 to 14.8) (p < 0.001). Follow-up catheterization 12 months later (37 patients) revealed a residual gradient of 6.7 +/- 6 mm Hg (95% CI 4.6 to 8.9); 3 (7%) of 43 patients had suboptimal results with development of recoarctation, defined as peak gradient >20 mm Hg, with successful repeat angioplasty. A small aneurysm developed at the site of dilation in 3 (7%) of the 43 patients. MRI follow-up data 1 to 10.8 years (mean 5.2 +/- 2.7) after angioplasty (37 patients) revealed no new aneurysm or appreciable change in the size of the preexisting aneurysm in the three patients. The blood pressure had normalized without medication in 27 (73%) of 37 patients at follow-up examination. CONCLUSIONS: Balloon angioplasty is safe and effective and should be considered a viable alternative to operation for treatment of discrete coarctation of the aorta in adolescents and adults.

Adolescent↗

[Primary pulmonary hypertension: a rare but often fatal complication of Crest syndrome].

In a retrospective study of 194 systemic sclerosis, we selected 37 Crest syndrome patients. Among these 37 patients, five presented a primary pulmonary hypertension. For three of these patients, the evolution of this primary pulmonary hypertension was rapidly fatal, one died of another cause. One died without certitude that death is imputable to HTAP. Diagnosis and management of the evolution of primary pulmonary hypertension may be easily assessed by doppler-echocardiography.

Aged↗

Surgical closure of macular hole using an absorbable macular plug.

BACKGROUND: The surgical management of macular holes has been a subject of controversy in recent years. Various techniques such as vitrectomy, membrane peeling, and gas tamponade with or without transforming growth factor-beta 2, and recently the use of autologous platelets have produced closure rates from 58% to 96%, depending on the stage of the hole. METHODS: The authors present preliminary results in a study of 19 consecutive patients with stage 3 or stage 4 macular hole who underwent vitrectomy followed by placement of an absorbable partially cross-linked gelatin plug in the macular hole. The vitreous cavity was filled with a nonexpanding gas or air alone; the patient was instructed to maintain prone positioning for 2-3 days. RESULTS: Anatomic attachment of the edges of the macular hole was achieved in 19 out of 19 patients with a minimum follow-up period of 6 months (average 11.5 months). CONCLUSIONS: A cross-linked gelatin plug can effectively reattach the edges of macular holes of stages 3 and 4. Its use is recommended only in macular holes in high myopes with posterior staphyloma or recurrent macular hole.

Absorption↗

Phenotypic characterization of cytokine expression in patients with IgA nephropathy.

To identify the cytokines that play a relevant role in the pathogenesis of IgA nephropathy, we analyzed and compared the gene expression of proinflammatory cytokines, immuno-regulatory cytokines, and growth factors in peripheral blood mononuclear cells (PBMC). Expression of IL-1 alpha, IL-1 beta, IL-2, IL-4, IL-6, IL-10, IL-12, IFN-gamma, TGF-beta, TNF-alpha, and PDGF was examined in 28 patients with IgA nephropathy (IgAN), 20 patients with non-IgA mesangial proliferative glomerulonephritis (mesPGN), and 19 healthy controls. Compared with healthy controls, a significant number of IgAN and mesPGN patients showed increased expression of IL-1 beta, IL-4, IL-10, IL-12, and IFN-gamma. The cytokine profile of renal tissue of 10 IgAN and 5 mesPGN biopsies was simultaneously analyzed and compared with that of PBMC. The proinflammatory IL-1 alpha and growth factor PDGF-B were expressed more in renal tissues than in PBMC. Furthermore, the renal profile of IL-alpha, IFN-gamma, and TNF-alpha expression was associated with the expression of IFN-gamma in PBMC. The serum level of IFN-gamma of IgAN correlated significantly (P = 0.0003) with that of IL-12, suggesting a potential role for cross-stimulation. More importantly, expression of IFN-gamma in PBMC and the elevated serum level correlated with the decline in glomerular filtration rate (P = 0.0012) and severity of renal histopathologic grade. To elucidate the role of leukocytes in renal cytokine expression, surface markers of T cells (CD3), monocytes (CD14), natural killer cells (CD16), and B cells (CD19) were also examined in renal tissues. The prominent renal expression of CD3, CD14, and CD16 implicates the leukocytes as the major source of proinflammatory cytokines in IgAN. Collectively, these findings indicate that IFN-gamma plays a prominent role in an interactive network of cytokines that contribute to the pathogenesis and progression of IgA nephropathy.

Adult↗

Impaired hepatosplenic elimination of circulating cryoglobulins in patients with essential mixed cryoglobulinaemia and hepatitis C virus (HCV) infection.

The pathogenic mechanisms that lead to renal deposition of the cryoprecipitable IgM rheumatoid factor-IgG complexes in essential mixed cryoglobulinaemia (EMC) are unknown. Defective removal of cryoprecipitable complexes from the circulation has been postulated in EMC-associated nephritis. To test this hypothesis, the kinetics and fate of a trace dose of 123I-radiolabelled autologous cryoglobulins were analysed in 13 patients with EMC grouped according to renal involvement. The time course of radioactivity distribution in the blood and organ uptake were measured by gamma camera scintigraphy. In blood sampled 30-300 s after injection, only a minor fraction (< 15%) of the circulating cryoglobulins bound to the erythrocytes, suggesting the elimination mechanisms are independent of binding to CR1 on erythrocytes. The overall blood disappearance curve showed a fast (< or = 1 min) and slow (> 4 h) biphasic pattern. In patients with quiescent or mild nepthritis, the liver and to a lesser extent the spleen were the major organs that mediated the rapid uptake and processing of the cryoglobulins from the circulation. In contrast, patients with active mesangiocapillary glomerulonephritis showed significantly (P < 0.001) less hepatic uptake, low liver-to-precordium ratio, and slower processing of cryoglobulins, prolonged liver mean transit time, than quiescent patients or mild nephritis patients. To elucidate the role and influence of HCV infection in the pathogenesis of EMC-nephritis, sera and cryoglobulins from all patients were assayed for HCV. None of the control group cases without nephritis showed any evidence of HCV-RNA in serum or cryoglobulin pellet. In contrast, all 10 EMC-nephritis patients' sera, and eight corresponding cryoglobulin pellets contained HCV-RNA. Collectively, these findings suggest an impaired reticuloendothelial system removal of IgM-IgG-HCV complexes may underlie their renal deposition.

Adult↗

Scintigraphy and ultrasonography in differentiating osteomyelitis from bone infarction in sickle cell disease.

PURPOSE: To demonstrate the combined use of scintigraphy and ultrasonography (US) in differentiating osteomyelitis from bone infarction in sickle cell disease. MATERIAL AND METHODS: Two patients with sickle cell disease were examined with a combination of bone, bone marrow, white blood cell and/or gallium scintigraphy and US. RESULTS: The scintigraphic studies demonstrated areas of suspected osteomyelitis at the distal femur in both patients and at the proximal right tibia in one of them. US revealed subperiosteal fluid collections in these areas. Aspiration guided by US established the presence of pus at the femur in both instances, which was successfully treated with the US-guided insertion of a drainage catheter and aspiration only, respectively. Thick blood, due to bone infarction, was aspirated at the tibia. CONCLUSION: The scintigraphic studies were useful in locating all areas of suspected osteomyelitis. The role of US was to confirm the presence of a subperiosteal fluid collection and to guide aspiration, which can show the distinction between a haematoma and an abscess.

Abscess↗

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↗