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Biomedical subjects

B Kahan

Publications and source records attributed to B Kahan.

At least 19 recordsLinked to original sources

Augmented enterocystoplasty for neurogenic bladder associated with renal transplantation: appearance on Tc-99m MAG3 renal transplant scan.

Enterocystoplasty (bladder augmentation) is a method of increasing bladder capacity in patients with small or neurogenic bladders in order to prevent vesicoureteral reflux. In patients with poorly compliant bladders, enterocystoplasty, which consists of a segment of detubularized small bowel or a portion of the stomach attached to the bladder, often helps to reduce the intravesicular pressures, thus reducing the likelihood of infection. It is also useful in treating bladder dysfunction in children with end-stage renal disease who require renal transplantation. Radiographic evaluation of patients with a renal transplant and augmented bladder often can be confusing, and may suggest a urine leak or hematoma. We report a patient with a renal transplant, bladder augmentation, and rising serum creatinine who underwent renal scintigraphy and ultrasonography.

Adult↗

Comparison of PRA-STAT, sHLA-EIA, and anti-human globulin-panel reactive antibody to identify alloreactivity in pretransplantation sera of heart transplant recipients: correlation to rejection and posttransplantation coronary artery disease.

BACKGROUND: Screening pretransplantation recipient sera for percent panel reactive antibodies (%PRA) by an anti-human globulin (AHG) assay may identify recipients who are at risk for graft rejection or development of posttransplantation coronary artery disease. However, the pretransplantation AHG-%PRA does not always correlate with the occurrence of graft rejection or coronary artery disease. METHODS: We compared the predictive capacity of the AHG-%PRA with that of an enzyme-linked immunoassay (EIA)-based PRA assay that identifies immunoglobulin G bound to soluble human leukocyte antigen (sHLA) class I molecules from pooled platelets of 240 random donors (sHLA-EIA), and that of an EIA-based assay that detects immunoglobulin G anti-HLA class I antibodies bound to sHLA derived from individual HLA-typed cell cultures (PRA-STAT). The pretransplantation sera from 130 cardiac allograft recipients were comparatively tested and results evaluated. RESULTS: Although AHG-%PRA- and sHLA-EIA-determined PRA results were comparable, neither assay discriminated potential recipients at risk for rejection or coronary artery disease. However, cardiac allograft recipients with pretransplantation PRA-STAT sera > 10% were at risk for (1) graft rejection (77% vs 56%, p < .05); (2) more rejections/recipient (1.9 vs 1.0, p < .02); (3) graft rejection within 30 days (92% vs 38%, p < .001); or (4) development of coronary artery disease (48% vs 23%, p < .05) than recipients with pretransplantation PRA-STAT sera < 10%. CONCLUSIONS: PRA-STAT analysis of pretransplantation sera from potential cardiac allograft recipients may be more clinically informative about HLA alloimmunity and a better predictor of adverse clinical events than either AHG-%PRA- or sHLA-EIA-determined PRA.

Antibody Specificity↗

Stability of renal allograft glomerular filtration rate associated with long-term use of cyclosporine A.

Renal allograft glomerular filtration rate (GFR) was measured at 4-month intervals for up to 1 year in 43 CsA-treated patients using x-ray fluorescence determination of plasma iohexol clearance. Study patients were divided into cohorts based on time (years) after transplantation at study entry (0-1; 1-2; 2-3; and > 3 years) and entry GFR levels (20-29; 30-39; 40-49; and > or = 50 ml/min/1.73 m2). GFR at study entry was 42 +/- 2 and was comparable in CAD (n = 31) versus LRD (n = 12) allografts (42 +/- 2 and 44 +/- 4 ml/min/1.73 m2, respectively). Range of entry GFR levels was similar in each of the "time at entry" cohorts defined above. Serum creatinine concentrations of 1.5-2.5 mg% were associated with GFR levels of 20-60 ml/min/1.73 m2. Serial GFR levels obtained at 4-month intervals for 1 year (n = 34 patients) were not consistent with a pattern of progressively declining GFR occurring as a function of either time after transplantation or absolute GFR level at study entry (intraindividual coefficient of variation 10.3 +/- 1.0%). Patients in the lower quartile of "entry GFR" levels (< 34 ml/min/1.73 m2) were more likely than their counterparts to have had a history of acute rejection. Results are consistent with retrospective population studies of aggregate serum creatinine levels, indicating that long-term CsA use is not uniformly associated with accelerated loss of renal allograft function consequent to a progressive, toxic nephropathy. The data also suggest that neither absolute GFR level nor time after transplantation represent indications for routine dose reduction or conversion to AZA.

Adult↗

Mechanisms and amelioration of acute renal allograft failure in the cyclosporine era.

The fairly wide-ranging spectrum of tactics under investigation for ameliorating acute renal allograft dysfunction caused by harvest/preservation-related ischemia, acute CsA nephrotoxicity, and acute immunologic crises reflect the fact that no single approach has emerged as universally useful for mitigating the vasomotor nephropathy produced by the combined effects of each of these vectors of vasomotor renal allograft injury. Given the clinical heterogeneity of patients and allografts, it is the author's bias that, in addition to careful donor and recipient hemodynamic management, induction immunosuppressive regimens should be individualized on the basis of allograft function in the immediate postreperfusion period (judged by rate of diuresis, intraoperative parenchymal tone, renal scan profiles, and rate of decline of serum creatinine concentration) as well as patient-specific immunologic and general medical risk factors. Promising laboratory and clinical investigations of such agents as calcium channel blockers, substances promoting intrarenal vasodilator vs. vasoconstrictor prostaglandin formation, and atriopeptins have the potential to provide clinically helpful options with regard to adjunctive therapy for ameliorating acute renal allograft dysfunction associated with INF and ACR.

Acute Kidney Injury↗

Detecting immunocomplex formation in sucrose gradients by enzyme immunoassay: application in determining epitope accessibility on ribosomes.

A sensitive method using enzyme immunoassay and sucrose gradient to analyze immunocomplexes of biological particles has been developed. The sensitivity and application of this method were demonstrated by that the in situ accessibility of ribosomal protein epitopes could be easily determined. We used sucrose gradients to separate the ribosome-bound and the free antibodies and traced the antibodies in the gradients by an enzyme-linked immunosorbent assay. Epitopes exposed in situ are bound by specific antibodies, which in turn are detected in sucrose gradients migrating with ribosomes. This method of detecting antibody migration is more sensitive than the conventional means of using A260nm to monitor the antibody-mediated dimerization of ribosomes. Furthermore, an epitope defined by a biotin-labeled monoclonal antibody can be analyzed in the presence of other unlabeled antibodies. Thus, the relationship of different accessible epitopes in situ can be readily examined. Versatility and sensitivity of this method should make it useful in analyzing a variety of immunocomplex systems.

Antibodies, Bacterial↗

Epitope mapping of monoclonal antibodies to Escherichia coli ribosomal protein S3.

The antigenic structure of Escherichia coli ribosomal protein S3 has been investigated by use of monoclonal antibodies. Six S3-specific monoclonal antibodies secreted by mouse hybridomas have been identified by immunoblotting of two-dimensional ribosomal protein separation gels. By using a competitive enzyme-linked immunosorbent assay, we have divided these monoclonal antibodies into three mutual inhibition groups, members of which are directed to three distinct regions of the S3 molecule. The independence of these monoclonal antibody-defined regions was confirmed by the failure of pairs of monoclonal antibodies from two inhibition groups to block the binding of biotinylated monoclonal antibodies of the third group. To determine the regions recognized by these monoclonal antibodies, chemically cleaved S3 peptides were fractionated by gel filtration and reverse-phase high-performance liquid chromatography. The fractionated peptides were coated on plates and examined for specific interaction with monoclonal antibody by enzyme immunoassay. In this manner, two epitopes have been mapped at the ends of the S3 molecule: one, in the last 22 residues, is recognized by three monoclonal antibodies; and the second, in the first 21 residues, is defined by two monoclonal antibodies. The third S3 epitope, recognized by a single monoclonal antibody, has been localized in a central segment of about 90 residues by gel electrophoresis and immunoblotting. These epitope-mapped monoclonal antibodies are valuable probes for studying S3 structure in situ.

Animals↗

Epitopes of Escherichia coli ribosomal protein S13.

To analyze the immunochemical structure of Escherichia coli ribosomal protein S13 and its organization in situ, we have generated and characterized 22 S13-specific monoclonal antibodies. We used a competitive enzyme-linked immunosorbent assay to divide them into groups based on their ability to inhibit binding of one another. The discovery of five groups with distinct binding properties suggested that a minimum of five distinct determinants on S13 are recognized by our monoclonal antibodies. The locations of the epitopes detected by these monoclonal antibodies have been mapped on S13 peptides. Three monoclonal antibodies bind a S13 C-terminal 34-residue segment. All the other 19 monoclonal antibodies bind a S13 N-terminal segment of about 80 residues. The binding sites of these 19 monoclonal antibodies have been further mapped to subfragments of peptides. Two monoclonal antibodies recognized S131-22; three monoclonal antibodies bound to S131-40; the binding sites of three other antibodies have been located in S1323-80, with epitopes possibly associated with residues 40-80. The remaining 11 monoclonal antibodies did not bind to these subfragments. These data provide molecular basis to the structure of S13 epitopes, whose in situ accessibility may reveal the S13 organization on the ribosome.

Amino Acids↗

Cyclosporine absorption in apancreatic dogs.

The plasma concentration time course of orally administered cyclosporine was studied in apancreatic dogs with established islet autografts and compared with that in normal control dogs. After oral administration of cyclosporine (20 mg/kg), blood samples were collected at 0, 1, 2, 3, 4, 6, 8, and 24 hours, and the plasma cyclosporine concentrations were measured by radioimmunoassay. The plasma level of cyclosporine increased promptly in both groups after dosing. Peak plasma concentrations ranged from 435 to 1,542 ng/ml and were attained at between 2 and 6 hours in the apancreatic dogs, and concentrations from 602 to 4,414 ng/ml were attained at between 1 and 6 hours in the control dogs. Even though there was substantial variation among animals, the plasma concentration curve of the apancreatic group was quite comparable with that of the control group. The Student's test for unpaired data failed to show any significant differences over the time course. Area under the concentration-time curves, maximum concentration, and times of peak concentration were calculated. These data demonstrated the capacity of apancreatic dogs with islet autografts to absorb cyclosporine when they are stable, nutritionally normal, and have full endocrine reconstitution.

Absorption↗

Early graft function.

1. Most of the first rejections occurred between the first and third weeks after transplantation, with the peak at 7 days. 2. Average serum creatinine values of 2 mg/dl were achieved in 2 days for living-related donor transplants. Cadaver donor grafts reached an average of 4 mg/dl by the tenth day, but in patients without rejection serum creatinine values of almost 2 mg/dl were achieved. 3. Cadaver donor grafts with cold ischemia times less than 12 hours led to the best early serum creatinine values. Cold ischemia times up to 48 hours and possibly beyond led to slightly higher creatinine levels but did not produce damage in proportion to the cold ischemia time. 4. Patients who were sensitized to more than 50% of the panel showed evidence of sensitization by having higher serum creatinine levels from one week to 3 weeks. 5. Even in the first few days after transplantation with a cadaver donor, black recipients had a higher serum creatinine than white recipients. The donor's race did not have a marked effect. 6. CsA doses given to cadaver donor recipients were about 2-4 mg/kg higher than living-related donor transplants. Patients experiencing a rejection episode were found to have been treated with about 1 mg/kg more than those without rejections. The corresponding blood levels of CsA were higher in the cadaver donor grafts and those with rejections. 7. Early serum creatinine levels were very strongly correlated with the one-year graft survival rate. Even one day after transplantation, the difference between patients with the best and worst one-day serum creatinine levels was as much as 30% in the one-year graft survival rate. At 2 weeks, the group with the best serum creatinine had a one-year survival rate that was 50 percentage points higher than the worst creatinine group. At one month, the best serum creatinine group had a one-year survival rate that was about 80 percentage points higher than the worst serum creatinine group. 8. Patients with high CsA levels of over 400 ng/ml in the early one-month posttransplant period, had poorer one-year graft survival than those with lower levels. The optimum level appeared to be less than 100 ng/ml by the tenth day and about 100-200 ng/ml to the third week posttransplant.(ABSTRACT TRUNCATED AT 400 WORDS)

Creatinine↗

Cyclosporin-A nephrotoxicity and acute cellular rejection in renal transplant recipients: correlation between radionuclide and histologic findings.

Serial radionuclide studies using both Tc-99m DTPA (perfusion) and I-131 hippuran (tubular function) were correlated with histologic findings in 25 patients with renal transplants. These cases included 15 cases of cyclosporin-A nephrotoxicity (CsA-NT) and ten cases of acute cellular rejection that were retrospectively selected on the basis of biopsy findings and favorable clinical response to therapy specific for each of these conditions. The serial radionuclide studies enabled the correct diagnosis in 12 of 15 cases of CsA-NT and eight of ten cases of acute rejection. Posttherapy radionuclide studies, furthermore, demonstrated improvement consistent with clinical response. In all cases, the radionuclide results were available at least 24 hours before biopsy findings. These results indicate that serial radionuclide studies evaluating interval changes in both perfusion and tubular function are of significant value in the diagnosis and follow-up of CsA-NT and acute cellular rejection in transplant recipients. This initial experience suggests a sensitivity of 80%.

Acute Disease↗

Early graft function.

1. The average serum creatinine level during the first 20 days after transplantation was lower in HLA-identical siblings than in parental donor transplants, suggesting an early effect of histocompatibility. 2. In rather small numbers of patients, the daily average serum creatinine values were not different with HLA-DR mismatching and HLA-B,DR mismatching, but were lower in the better matched transplants for the HLA-A,B loci and the HLA-A,B,DR loci. 3. The average serum creatinine values in the first 20 days after transplantation were correlated with the one-year graft survival rates. Those patients with serum creatinine levels less than 2.4 mg/dl had one-year graft survival rates of over 80% compared with those with serum creatinine levels above 7.5 mg/dl after the first week who had one-year graft survival rates about 30% less. Intermediate serum creatinine values yielded intermediate one-year graft survival rates. 4. The cyclosporine dosage in the first month after transplantation varied considerably among the four centers studied here. These values were not directly correlated with the one-year graft survival rate, average serum creatinine levels or cumulative rejection rates in this preliminary examination. 5. Patients who rejected transplants 11 to 60 days posttransplant had been given lower cyclosporine dosages than those who rejected early or who had no rejections. 6. Although firm conclusions cannot be drawn from the small numbers of patients encompassed in this study, we hope the potential value of this type of analysis will be realized.

Creatinine↗

Differential control of U1 small nuclear RNA expression during mouse development.

During normal mouse development the relative amounts of two types of U1 small nuclear RNA's (U1 RNA) change significantly. Fetal tissues have comparable levels of the two major types of mouse U1 RNA's, mU1a and mU1b, whereas most differentiated adult tissues contain only mU1a RNA's. Those adult tissues that also accumulate detectable amounts of embryonic (mU1b) RNA's (for example, testis, spleen, and thymus) contain a significant proportion of stem cells capable of further differentiation. Several strains of mice express minor sequence variants of U1 RNA's that are subject to the same developmental controls as the major types of adult and embryonic U1 RNA. The differential accumulation of embryonic U1 RNA's may influence the pattern of gene expression during early development and differentiation.

Aging↗