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Biomedical subjects

M A Simpson

Publications and source records attributed to M A Simpson.

At least 19 recordsLinked to original sources
PubMed2006

Improved survival after live donor adult liver transplantation (LDALT) using right lobe grafts: program experience and lessons learned.

We present our program experience with 85 live donor adult liver transplantation (LDALT) procedures using right lobe grafts with five simultaneous live donor kidney transplants using different donors performed over a 6-year period. After an "early" 2-year experience of 25 LDALT procedures, program improvements in donor and recipient selection, preoperative imaging, donor and recipient surgical technique and immunosuppressive management significantly reduced operative mortality (16% vs. 3.3%, p = 0.038) and improved patient and graft 1-year survival in recipients during our "later" experience with the next 60 cases (January 2001 and March 2005; patient survival: early 70.8% vs. later 92.7%, p = 0.028; graft survival: Early 64% vs. later 91.1%, p = 0.019, respectively). Overall patient and graft survival were 82% and 80%. There was a trend for less postoperative complications (major and minor) with program experience (early 88% vs. later 66.7%; p = 0.054) but overall morbidity remained at 73.8%. Biliary complications (cholangitis, disruption, leak or stricture) were not influenced by program experience (early 32% vs. later 38%). Liver volume adjusted to 100% of standard liver volume (SLV) within 1 month post-transplant. Despite a high rate of morbidity after LDALT, excellent patient and graft survival can be achieved with program experience.

Adolescent↗
PubMed2005

Complicated hereditary spastic paraplegia with thin corpus callosum (HSP-TCC) and childhood onset.

The hereditary spastic paraplegias (HSPs) are a group of rare disorders with the predominant clinical feature of progressive spastic paraplegia. They are subdivided into pure and complicated forms according to whether the disorder is associated with other neurological abnormalities. We report on two unrelated female Caucasian patients with complicated HSP, aged 16 and 24 years, who showed progressive gait disturbance with spasticity and ataxia as well as cognitive impairment. Onset of symptoms was at age 3 and 10 years, respectively. MRI revealed mild diffuse non-progressive T (2)-signal alterations of cerebral white matter and thinning of the body and genu of the corpus callosum. Some similarity of clinical symptoms and MRI patterns with the phenotype of Mast syndrome prompted a mutation analysis of the SPG21 gene, encoding maspardin, which revealed a wild-type sequence in both patients. Clinical and neuroradiological features in our patients are diagnostic for complicated autosomal recessive hereditary spastic paraplegia with thin corpus callosum (HSP-TCC, SPG11). This disorder, characterized by a typical MRI pattern and a progressive spastic paraplegia that may be associated with dementia and ataxia, may have an onset in early childhood and probably is one of the more common forms of complicated HSP.

Adolescent↗
PubMed2002

Diagnostic strategies in CADASIL.

BACKGROUND: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited autosomal dominant condition characterized by migraine, recurrent stroke, and dementia. It results from mutations in the notch3 gene but mutations may occur at multiple sites making molecular diagnosis time consuming. It has been suggested that the presence of granular osmiophilic material (GOM) on skin biopsy and involvement of the anterior temporal lobe and external capsule on MRI may help in diagnosis. METHODS: The authors identified 83 potential index cases from the British population and screened exons 2 to 23 of notch3. MRI scans were scored using a modified Scheltens scale. Skin biopsy was performed in a subgroup. RESULTS: Fifteen different point mutations were identified in 48 families, 73% of which were in exon 4, 8% in exon 3, and 6% in each of exons 5 and 6. Moderate or severe involvement of the anterior temporal pole on MRI had a sensitivity of 89% and specificity of 86% for diagnosis of CADASIL, whereas external capsule involvement had a high sensitivity of 93% but a low specificity of 45%. Skin biopsy, performed in 18 cases, had a sensitivity of 45% and specificity of 100%. CONCLUSIONS: The spectrum of mutations in this study can be used to plan appropriate screening protocols; a suggested protocol is to screen exon 4, and proceed to exons 3, 5, and 6 where indicated. GOM on skin biopsy is diagnostic but can be negative. Anterior temporal pole involvement on MRI is a useful diagnostic marker.

Adult↗
PubMed2001

Melanoma chondroitin sulfate proteoglycan regulates matrix metalloproteinase-dependent human melanoma invasion into type I collagen.

Tumor cell adhesion and proteolysis of the extracellular matrix proteins surrounding the cells are tightly linked processes in tumor invasion. In this study, we sought to identify components of the cell surface of a vertical growth phase melanoma cell line, WM1341D, that mediate invasive cellular behavior. We determined by antisense inhibition that melanoma chondroitin sulfate proteoglycan (MCSP) and membrane-type 3 matrix metalloproteinase (MT3-MMP) expressed on WM1341D are required for invasion of type I collagen and degradation of type I gelatin. MT3-MMP co-immunoprecipitated with MCSP in WM1341D melanoma cells cultured on type I collagen or laminin. The association between MT3-MMP and MCSP was largely disrupted by removing chondroitin sulfate glycosaminoglycan (CS) from the cell surface, suggesting CS could mediate the association between the two cell surface core proteins. Recombinant MT3-MMP and MT3-MMP from whole cell lysates of WM1341D cells were specifically eluted from CS- conjugated affinity columns. The results indicate that MT3-MMP possesses the potential to promote melanoma invasion and proteolysis and that the formation of a complex between MT3-MMP and MCSP may be a crucial step in activating these processes.

Animals↗
PubMed2001

Hyaluronan synthase elevation in metastatic prostate carcinoma cells correlates with hyaluronan surface retention, a prerequisite for rapid adhesion to bone marrow endothelial cells.

Bone marrow is the primary site of metastasis in patients with advanced stage prostate cancer. Prostate carcinoma cells metastasizing to bone must initially adhere to endothelial cells in the bone marrow sinusoids. In this report, we have modeled that interaction in vitro using two bone marrow endothelial cell (BMEC) lines and four prostate adenocarcinoma cell lines to investigate the adhesion mechanism. Highly metastatic PC3 and PC3M-LN4 cells were found to adhere rapidly and specifically (70-90%) to BMEC-1 and trHBMEC bone marrow endothelial cells, but not to human umbilical vein endothelial cells (15-25%). Specific adhesion to BMEC-1 and trHBMEC was dependent upon the presence of a hyaluronan (HA) pericellular matrix assembled on the prostate carcinoma cells. DU145 and LNCaP cells were only weakly adherent and retained no cell surface HA. Maximal BMEC adhesion and HA encapsulation were associated with high levels of HA synthesis by the prostate carcinoma cells. Up-regulation of HA synthase isoforms Has2 and Has3 relative to levels expressed by normal prostate corresponded to elevated HA synthesis and avid BMEC adhesion. These results support a model in which tumor cells with up-regulated HA synthase expression assemble a cell surface hyaluronan matrix that promotes adhesion to bone marrow endothelial cells. This interaction could contribute to preferential bone metastasis by prostate carcinoma cells.

Biomarkers, Tumor↗
PubMed2000

GATA zinc finger interactions modulate DNA binding and transactivation.

GATA-1 and other vertebrate GATA factors contain a DNA binding domain composed of two adjacent homologous zinc fingers. Whereas only the C-terminal finger of GATA-1 is capable of independent binding to the GATA recognition sequence, double GATA sites that require both fingers for high affinity interaction are found in several genes. We propose a mechanism whereby adjacent zinc fingers interact to influence the binding and transactivation properties of GATA-1 at a subset of DNA-binding sites. By using two such double GATA sites we demonstrate that the N-terminal finger and adjacent linker region can alter the binding specificity of the C-terminal finger sufficiently to prevent it from recognizing some consensus GATA sequences. Therefore, the two zinc fingers form a composite binding domain having a different DNA binding specificity from that shown by the constituent single C-terminal finger. Furthermore, we compare two of these double sites and show that high affinity binding of GATA-1 to a reporter gene does not necessarily induce transactivation, namely the sequence of the DNA-binding site can alter the ability of GATA-1 to stimulate transcription.

ATP-Binding Cassette Transporters↗
PubMed2000

The abilities of children with mental retardation to remember personal experiences: implications for testimony.

Investigated the abilities of children with mental retardation to remember the details of a personally experienced event. A simulated health check was administered to 20 children with mental retardation and 40 normally developing children, half matched on mental age (MA) and half matched on chronological age (CA) with the children with mental retardation. The children's memory was assessed immediately after the health check and 6 weeks later. Overall, the children with mental retardation accurately recalled the health check features, provided detail, and resisted misleading questions about features that did not occur. The group with mental retardation performed similarly to the MA matches on virtually all of the memory variables. The children with mental retardation performed worse than the CA matches on most of the memory variables, although they were able to recall a similar number of features. The findings are discussed in terms of the ability of children with mental retardation to provide accurate testimony.

Adolescent↗
PubMed1999

Melanoma chondroitin sulphate proteoglycan regulates cell spreading through Cdc42, Ack-1 and p130cas.

Melanoma chondroitin sulphate proteoglycan (MCSP) is a cell-surface antigen that has been implicated in the growth and invasion of melanoma tumours. Although this antigen is expressed early in melanoma progression, its biological function is unknown. MCSP can stimulate the integrin-alpha4 beta1-mediated adhesion and spreading of melanoma cells. Here we show that stimulated MCSP recruits tyrosine-phosphorylated p130 cas, an adaptor protein important in tumour cell motility and invasion. MCSP stimulation also results in a pronounced activation and recruitment of the Rho-family GTPase Cdc42. MCSP-induced spreading of melanoma cells is dependent upon active Cdc42, a Cdc42-associated tyrosine kinase (Ack-1) and tyrosine phosphorylation of p130cas. Furthermore, vectors inhibiting Ack-1 or Cdc42 expression and/or function abrogate MCSP-induced tyrosine phosphorylation and recruitment of p130cas. Our findings indicate that MCSP may modify tumour growth or invasion by a unique signal-transduction pathway that links Cdc42 activation to downstream tyrosine phosphorylation and subsequent cytoskeletal reorganization.

Cell Movement↗
PubMed1999

Targeted disruption of the adipocyte lipid-binding protein (aP2 protein) gene impairs fat cell lipolysis and increases cellular fatty acid levels.

The availability of mice containing an adipocyte lipid-binding protein (ALBP/aP2) gene disruption allowed for a direct examination of the presumed role of lipid-binding proteins in the mobilization and trafficking of intracellular fatty acids. Total body and epididymal fat pad weights, as well as adipose cell morphology, were unaltered in male ALBP/aP2 disrupted mice when compared to their wild-type littermates. Analysis of adipocytes isolated from wild-type and ALBP/aP2 null mice revealed that a selective 40- and 13-fold increase in the level of the keratinocyte lipid-binding protein (KLBP) mRNA and protein, respectively, accompanied the ALBP/aP2 gene disruption. Although KLBP protein was significantly up-regulated, the total lipid-binding protein level decreased 8 -fold as a consequence of the disruption. There was no appreciable difference in the rate of fatty acid influx or esterification in adipocytes of wild-type and ALBP/aP2 null animals. To the contrary, basal lipolysis decreased approximately 40% in ALBP/aP2 nulls as compared to wild-type littermates. The glycerol release from isproterenol-stimulated ALBP/aP2 null fat cells was similarly reduced by approximately 35%. Consistent with a decrease in basal efflux, the non-esterified fatty acid (NEFA) level was nearly 3-fold greater in adipocytes from ALBP/aP2 nulls as compared to wild-type animals. The significant decrease in both basal and isoproterenol-stimulated lipolysis in adipose tissue of ALBP/aP2 null mice supports the model whereby intracellular lipid-binding proteins function as lipid chaperones, facilitating the movement of fatty acids out of the fat cell.

Adipocytes↗
PubMed1999

Biochemical and biophysical analysis of the intracellular lipid binding proteins of adipocytes.

Adipocytes express two lipid-binding proteins; the major one termed the adipocyte lipid-binding protein or aP2 (ALBP/aP2) and a minor one referred to as the keratinocyte lipid-binding protein (KLBP). In order to evaluate the potential physiological roles for these proteins, their biochemical and biophysical properties have been analyzed and compared. ALBP/aP2 and KLBP exhibit similar binding affinities for most long-chain fatty acids; however, ALBP/aP2 exhibits a two to three-fold increased affinity for myristic, palmitic, oleic and linoleic acids, the predominant fatty acids of adipocytes. As measured by guanidinium hydrochloride denaturation, the stability of ALBP/aP2 is nearly 3 kcal/mol greater than that of KLBP. While the pI of ALBP/aP2 was determined to be 9.0, that of KLBP is 6.5 suggesting differing net charges at physiological pH. Analysis of surface electrostatic properties of ALBP/aP2 and KLBP revealed similar charge polarity, although differences in the detailed charge distribution exist between the proteins. The distribution of hydrophobic patches was also different between the proteins,ALBP/aP2 has only scattered hydrophobic surfaces while KLBP has a large hydrophobic patch near the ligand portal into the binding cavity. In sum, these results point out that despite the striking similarity between ALBP/aP2 and KLBP in tertiary structure, significant differences in ligand binding and surface properties exist between the two proteins. Hence, while it is tempting to speculate that ALBP/aP2 and KLBP are metabolically interchangeable, careful analysis suggests that the two proteins are quite distinct and likely to play unique metabolic roles.

Amino Acid Sequence↗
PubMed1998

Analysis of a series of phenylalanine 57 mutants of the adipocyte lipid-binding protein.

The importance of phenylalanine 57, an adipocyte lipid-binding protein (ALBP) portal residue, to ligand affinity and specificity has been investigated using a series of ALBP position 57 mutants. In wild-type ALBP, phenylalanine 57 undergoes a side chain rotation upon ligand binding, moving from an inwardly oriented, ligand-exclusive position in apoprotein structures to an outwardly oriented position in the holoprotein. To examine the role of F57 side chain rotation in the apoprotein-holoprotein transition and in ligand selectivity, ALBP site-specific mutants F57A, F57G, F57H, and F57W were expressed in Escherichia coli and purified to homogeneity. Mutants were analyzed for binding characteristics and stability toward chemical denaturation, and energy-minimized models of each mutant were constructed using apo, oleate-, and arachidonate-bound ALBP crystallographic coordinates. The stability of ALBP forms (wtALBP approximately F57G > F57A > F57W > F57H) was unrelated to the affinity of ALBP forms (wtALBP approximately F57W > F57H > F57G > F57A) for various lipids and did not vary between fatty acids. Since ligand selectivity was maintained between wild type and all mutants while ligand affinity was grossly diminished, we conclude that phenylalanine 57 is critical to the formation of the fatty acid/ALBP complex, but is uninvolved in determination of selectivity over the range of physiological ligands tested.

Adipocytes↗
PubMed1998

Increased lithium serum and red blood cell concentrations during ketorolac coadministration.

Case reports of a lithium-ketorolac drug interaction have been published, but no formal investigation of this interaction has been conducted. The objective of the study presented here was to determine significant changes in lithium serum and red blood cell (RBC) concentrations after lithium and ketorolac (oral formulation) coadministration at steady-state conditions. Five healthy men participated in the study and received lithium 900 mg/day (300 mg in the morning and 600 mg at bedtime) for 13 days. Ketorolac 40 mg/day (10 mg four times a day) was added on days 8 through 12. Ten blood samples were obtained on days 7 and 13 to determine area under the concentration-time curve (AUC) lithium serum and RBC concentrations. Serum and RBC lithium concentrations were assayed by atomic absorption spectrophotometry with an intra-assay coefficient of variation (CV) of 1.2% on day 1 (range 0-1.0 microg/mL) and 4.9% (range 0-1.0 microg/mL) on day 2 and an interassay CV of 2.9% (range 0-1.0 microg/mL) on days 1 and 2 of serum analysis and a CV of 5.3% (range 0-0.3 microg/mL) of RBC concentrations. Total serum AUC lithium and RBC AUC values significantly increased by 24% (p < 0.02) and by 27% (p < 0.05) with the ketorolac coadministration, respectively. An increased incidence and severity of lithium-associated side effects were reported during concomitant administration. A clinically significant drug interaction can occur when ketorolac is added to lithium therapy.

Adult↗
PubMed1997

Biochemical and crystallographic analyses of a portal mutant of the adipocyte lipid-binding protein.

A number of crystallographic studies of the adipocyte lipid-binding protein have established that the fatty acid-binding site is within an internalized water-filled cavity. The same studies have also suggested the existence of a region physically distinct from the fatty acid-binding site which connects the cavity of the protein with the external solvent, hereafter referred to as the portal. In an effort to examine the portal region, we have used site-directed mutagenesis to introduce the mutations V32D/F57H into the murine ALBP cDNA. Mutant protein has been isolated, crystallized, and its stability and binding properties studied by biochemical methods. As assessed by guanidine-HCl denaturation, the mutant form exhibited a slight overall destabilization relative to the wild-type protein under both acid and alkaline conditions. Accessibility to the cavity in both the mutant and wild-type proteins was observed by stopped-flow analysis of the modification of a cavity residue, Cys117, by the sulfhydryl reactive agent 5, 5'-dithiobis(2-nitrobenzoic acid) at pH 8.5. Cys117 of V32D/F57H ALBP was modified 7-fold faster than the wild-type protein. The ligand binding properties of both the V32D/F57H mutant and wild-type proteins were analyzed using a fluorescent probe at pH 6.0 and 8.0. The apparent dissociation constants for 1-anilinonaphthalene-8-sulfonic acid were approximately 9-10-fold greater than the wild-type protein, independent of pH. In addition, there is a 6-fold increase in the Kd for oleic acid for the portal mutant relative to the wild-type at pH 8.0. To study the effect of pH on the double mutant, it was crystallized and analyzed in two distinct space groups at pH 4.5 and 6.4. While in general the differences in the overall main chain conformations are negligible, changes were observed in the crystallographic structures near the site of the mutations. At both pH values, the mutant side chains are positioned somewhat differently than in wild-type protein. To ensure that the mutations had not altered ionic conditions near the binding site, the crystallographic coordinates were used to monitor the electrostatic potentials from the head group site to the positions near the portal region. The differences in the electrostatic potentials were small in all regions, and did not explain the differences in ligand affinity. We present these results within the context of fatty acid binding and suggest lipid association is more complex than that described within a single equilibrium event.

Anilino Naphthalenesulfonates↗
PubMed1997

Regulation of gene expression in adipose cells by polyunsaturated fatty acids.

In fat cells polyunsaturated fatty acids are both substrates for, and products of, triacylglycerol metabolism. Dietary fatty acids are efficiently incorporated into the triacylglycerol droplet under lipogenic conditions while rapidly mobilizing them during lipolytic stimulation. Hence, the flux and magnitude of the fatty acid pool in adipocytes is constantly changing in response to hormonal, metabolic and genetic determinants. Due to the rapidly changing flux of fatty acids, the majority of genes encoding enzymes and proteins of lipid metabolism are largely refractory to long-term regulatory control by fatty acids. Only at extremes of high or low lipid levels, or under pathophysiological conditions, do adipose genes respond by up- or down-regulating gene expression. Despite the lack of responsiveness to lipids in adipose tissue, a surprisingly large number of genes have been characterized recently as lipid responsive when assayed in heterologous systems. These observations suggest an endogenous negative element exists in the lipid signaling pathway in adipocytes. The major intracellular lipid binding protein in adipose cells is the adipocyte lipid binding protein (ALBP), the product of the aP2 gene. This protein is 15 kDa, abundant and found exclusively in the cytoplasm of adipocytes. The protein binds fatty acids and related lipids in a 1:1 stoichiometry within a large water filled interior cavity. The lipid binding protein forms high affinity associations with polyunsaturated fatty acids such as arachidonic acid (Kd approximately 250 nM) but not with prostaglandins of the E, D or J series (Kd > 4 microM). The upstream region of the aP2 gene contains a peroxisome-proliferator activated receptor response element which associates with PPARs to regulate its expression. A positive autoregulatory circuit exists to upregulate lipid binding protein expression when polyunsaturated fatty acid levels are increased. Analysis of adipose tissue from aP2 null animals generated by a targeted disruption revealed that the partial loss of ALBP expression in heterozygotes and complete lack of ALBP in the nulls was accompanied by a compensatory up-regulation of the keratinocyte lipid binding protein. However, the total amount of lipid binding protein in the nulls was less than 15% that in the wild type littermates. No evidence was found for upregulation of other lipid binding proteins such as the heart FABP or liver FABP. In aP2 nulls, the fatty acid composition was unaltered but the mass of fatty acid per gram tissue more than doubled relative to wild type. In heterozygotes, the level of fatty acid was intermediate to that of wild-type and nulls, consistent with an intermediate level of lipid binding protein. These results indicate that the fatty acid pool level in adipocytes is inversely correlated with the amount of lipid binding protein. Since prostaglandin biosynthesis is dependent upon polyunsaturated fatty acid substrates, the intracellular lipid binding proteins control accessibility of substrates of the prostanoid pathway. Intracellular lipid binding proteins therefore are negative elements in polyunsaturated fatty acid control of gene expression.

Adipose Tissue↗
PubMed1997

Intracellular lipid-binding proteins and their genes.

Intracellular lipid-binding proteins are a family of low-molecular-weight single-chain polypeptides that form 1:1 complexes with fatty acids, retinoids, or other hydrophobic ligands. These proteins are products of a large multigene family of unlinked loci distributed throughout the genome. Each lipid-binding protein exhibits a distinctive pattern of tissue distribution. Transcriptional control, regulated by a combination of peroxisome proliferator activated receptors and CCAAT/enhancer-binding proteins, allows for a variety of both cell and tissue-specific expression patterns. In some cells, fatty acids increase the expression of the lipid-binding protein genes. Fatty acids, or their metabolites, are activators of the peroxisome proliferator-activated receptor family of transcription factors. Therefore, as the concentration of lipid in the diet increases, the expression of lipid-binding proteins coordinately increases. As revealed by X-ray crystallography, the lipid-binding proteins fold into beta-barrels, forming a large internal water-filled cavity. Fatty acid ligands are bound within the cavity, occupying only about one-third of the accessible volume. The bound fatty acid is stabilized via a combination of enthalpic and entropic forces that govern ligand affinity and selectivity. Cytoplasmic lipid-binding proteins are the intracellular receptors for hydrophobic ligands, delivering them to the appropriate site for use as metabolic fuels and regulatory agents.

Amino Acid Sequence↗
PubMed1996

A multicenter trial of FK506 (tacrolimus) therapy in refractory acute renal allograft rejection. A report of the Tacrolimus Kidney Transplantation Rescue Study Group.

A multicenter trial was conducted to evaluate the efficacy and safety of tacrolimus in the treatment of refractory renal allograft rejection. Renal transplant recipients experiencing biopsy-proven recurrent acute allograft rejection were eligible if the current rejection episode was refractory to corticosteroids. A total of 73 patients were enrolled, of whom 59 (81%) had previously received at least one course of antilymphocyte antibody as rejection therapy. One-year follow-up was available in 93% of patients. Median time to tacrolimus rescue therapy was 75 days after transplantation (range, 18-1448 days). Therapeutic responses to tacrolimus included improvement in 78% of patients, stabilization in 11%, and progressive deterioration in 11%. The risk of experiencing progressive deterioration was related to the pretacrolimus serum creatinine level: serum creatinine < or = mg/dl, 3%; 3.1-5 mg/dl, 16% (P < 0.04); > 5 mg/dl, 23% (P < 0.02). Twelve-month (from the time of initiation of tacrolimus therapy) actuarial patient and graft survival rates were 93% and 75%. Graft loss occurred in 19 patients (25%) at a median time of 108 days. Fourteen episodes of recurrent rejection were diagnosed in 10 patients (14%), at a median time of 101 days. Eleven episodes of recurrent rejection were treated (three patients underwent transplant nephrectomy), with resolution achieved in nine patients. Antilymphocyte antibody therapy was not used to treat recurrent rejection. Serum creatinine values improved during tacrolimus therapy: median serum creatinine level before tacrolimus, 3.2 mg/dl; median at 1 year after tacrolimus, 1.8 mg/dl. Twelve infections were documented in 11 patients (15%), including cytomegalovirus infection in three patients (4%). Posttransplant lymphoproliferative disorder was diagnosed in a single patient. Tacrolimus whole blood levels averaged 15.0 +/- 9.9 ng/ml at day 7 of tacrolimus therapy and 9.4 +/- 5.1 ng/ml at 1 year, and were consistent among individual centers. Treatment outcome did not correlate with tacrolimus blood levels. The most commonly observed adverse events were neurological and gastrointestinal. Seventy-four percent of patients received tacrolimus for at least 1 year. Tacrolimus therapy was discontinued in 18% of patients for rejection (11% for progressive, unrelenting rejection, and 7% for recurrent rejection). Tacrolimus therapy was discontinued in 8% of patients due to adverse events. In conclusion, tacrolimus rescue therapy provides (1) prompt, effective reversal of refractory renal allograft rejection, (2) good long-term renal allograft function, (3) a low incidence of recurrent rejection, and (4) an acceptable safety profile in renal allograft recipients experiencing refractory rejection.

Acute Disease↗