The suppressive effect on CD4 T cell alloresponse against endothelial HLA-DR via PD-L1 induced by anti-A/B ligation.

While donor-specific human leukocyte antigen (HLA) antibodies are a frequent cause for chronic antibody-mediated rejection in organ transplantation, this is not the case for antibodies targeting blood group antigens, as ABO-incompatible (ABO-I) organ transplantation has been associated with a favorable graft outcome. Here, we explored the role of CD4 T cell-mediated alloresponses against endothelial HLA-D-related (DR) in the presence of anti-HLA class I or anti-A/B antibodies. CD4 T cells, notably CD45RA-memory CD4 T cells, undergo extensive proliferation in response to endothelial HLA-DR. The CD4 T cell proliferative response was enhanced in the presence of anti-HLA class I, but attenuated in the presence of anti-A/B antibodies. Microarray analysis and molecular profiling demonstrated that the expression of CD274 programmed cell death ligand 1 (PD-L1) increased in response to anti-A/B ligation-mediated extracellular signal-regulated kinase (ERK) inactivation in endothelial cells that were detected even in the presence of interferon-γ stimulation. Anti-PD-1 antibody enhanced CD4 T cell proliferation, and blocked the suppressive effect of the anti-A/B antibodies. Educated CD25+ CD127- regulatory T cells (edu.Tregs ) were more effective at preventing CD4 T cell alloresponses to endothelial cells compared with naive Treg ; anti-A/B antibodies were not involved in the Treg -mediated events. Finally, amplified expression of transcript encoding PD-L1 was observed in biopsy samples from ABO-I renal transplants when compared with those from ABO-identical/compatible transplants. Taken together, our findings identified a possible factor that might prevent graft rejection and thus contribute to a favorable outcome in ABO-I renal transplantation.

Serum αKlotho as a Predictor of Graft Dysfunction After Kidney Transplantation.

OBJECTIVE: To improve the long-term survival rate after kidney transplantation (KTx), allograft injury should be identified as soon as possible. Regardless of aggressive immunosuppressive therapies, recipients of kidney transplants still have a significant risk of graft failure. No specific predictor for the progression of chronic kidney disease (CKD) after KTx has yet been found. Aberrant molecular mechanisms involving the αKlotho-fibroblast growth factor (FGF) 23 axis may be a useful determinant of renal impairment and graft failure over time. METHODS: Plasma and spot urine samples were collected from 47 patients 1 year after KTx. Evaluation of renal function after KTx was performed using levels of biomarkers including serum intact FGF23, soluble αKlotho, 25(OH) vitamin D (25(OH)D), and the difference in the estimated glomerular filtration rate (eGFR) between the first and third year after KTx (ΔeGFR). RESULTS: The median serum αKlotho, intact FGF23, and 25(OH)D were 516.3 pg/mL, 58.7 pg/mL, and 5.7 ng/mL, respectively. No marked changes in the standard biomarkers that regulate phosphate homeostasis were found. Serum αKlotho levels were associated with ΔeGFR. Multivariate regression analysis revealed that serum αKlotho levels significantly predicted a decrease in eGFR in the graft kidney 2 years after KTx, but serum 25(OH)D and FGF23 levels were not significant. Serum αKlotho levels showed an inverse correlation with fractional excretion of magnesium, which reflects tubular injury in the early stage of CKD. CONCLUSION: Measurement of serum αKlotho may serve as a useful predictor of KTx patients who require initiation of pre-emptive medication.

Efficacy of Eculizumab Therapy for Atypical Hemolytic Uremic Syndrome Recurrence and Antibody-Mediated Rejection Progress After Renal Transplantation With Preformed Donor-Specific Antibodies: Case Report.

Atypical hemolytic uremic syndrome (aHUS) develops as the result of unregulated complement progression and precipitates de novo thrombotic microangiopathy. Plasma therapy is used to control the progression of the complement cascade, but that therapy is not effective in all patients and is accompanied by risk of infection and/or allergy. Eculizumab has been reported as an efficient therapy for aHUS. We report the case of a 35-year old woman who underwent effective eculizumab therapy for aHUS recurrence and antibody-mediated rejection (AMR) progress after renal transplantation with preformed donor-specific antibodies (DSA). She developed end-stage renal disease due to suspicious IgA nephropathy at age 33 years. Kidney transplantation was performed at age 35 years, and aHUS recurred 2 weeks later, leading to the progressive hemolytic anemia and renal dysfunction. Therefore, she underwent plasma therapy several times. Because it was difficult to continue to plasma therapy for severe allergy, eculizumab was proposed as an alternate therapy. Treatment with eculizumab was initiated 36 days after renal transplantation. After 3 years of eculizumab treatment, and without plasma therapy, schistocytes decreased, haptoglobin increased to within normal limits, creatinine levels stabilized, and no further episodes of diarrhea were reported. At protocol biopsy 1 year after transplantation, she was diagnosed with C4d-negative subclinical AMR. However, her pathologic findings at follow-up biopsy 3 years after transplantation were recovered. We conclude that eculizumab alone, without plasma therapy, is sufficient to treat recurrence of aHUS and AMR due to DSA after renal transplantation and to maintain long-term graft function.

Pleomorphic lobular carcinoma of the breast: a comparison of cytopathological features with other lobular carcinoma variants.

OBJECTIVE: Pleomorphic lobular carcinoma (PLC) is a subtype of breast cancer with unique morphological features, but it remains controversial whether PLC should be considered an independent disease entity. The aim of this study was to illustrate cytopathological characteristics of PLC in comparison with other lobular carcinoma variants. METHODS: We investigated clinicopathological features of PLC (n = 11) compared with those of other variants of invasive lobular carcinoma (ILC, non-PLC) (n = 32). Histological variants of the non-PLC group consisted of classic (n = 25), solid (n = 2), alveolar (n = 1) and a tubulolobular type (n = 4). A review of cytological reports and fine needle aspiration (FNA) smear samples was performed for the PLC (n = 9) and non-PLC (n = 27) groups. RESULTS: Patients with PLC were older, and had a higher nuclear grade and a higher incidence of axillary lymph node metastasis and triple negative phenotype than non-PLC patients (P = 0.007, P < 0.001, P = 0.02 and P < 0.001, respectively). Cytological findings in PLC included medium- to large-sized nuclei, prominent nucleoli, a moderate-to-severe degree of pleomorphism, apocrine change and background necrosis, none of which were evident in the smears of the non-PLC group (P < 0.001, P = 0.002, P < 0.001, P < 0.001, and P = 0.03, respectively). Despite these differences, patients with PLC and non-PLC showed similar clinical outcomes in our follow-up period. CONCLUSIONS: Based on our results, a cytological diagnosis of PLC should be proposed if there are moderate- to large-sized nuclei, prominent nucleoli, a moderate-to severe degree of nuclear pleomorphism, apocrine change and necrosis in the background in FNA biopsy samples.

Mucinous carcinoma of the breast: a comparative study on cytohistological findings associated with neuroendocrine differentiation.

OBJECTIVE: Mucinous carcinoma (MCA) may show neuroendocrine differentiation (ND), but the cytological features characteristic of ND remains elusive. We compared fine needle aspiration (FNA) findings of MCA between cases with high and low degrees of ND. METHODS: Histological sections of 37 MCA cases were immunohistochemically evaluated for expression of chromogranin A and synaptophysin, and were graded as 0 to 3+ degrees of ND. They were divided into low ND (grade 0 and 1+) and high ND (grade 2+ and 3+) groups. Pre-operative FNA samples of each group were assessed for cytological features. RESULTS: The mean age of the high ND group (n = 18) was higher than the low ND group (n = 19, P = 0.01). In FNA samples of the high ND group, 17 cases showed moderate to severe degrees of discohesiveness, but low ND cases mainly showed no or only mild discohesiveness (P < 0.001). Nine of the low ND cases displayed overlapped, cohesive cell clusters, whereas, in the high ND cases, the cells were arranged in a loose, flat and monolayered pattern (P = 0.045). Fourteen of the high ND cases had round nuclei, but oval nuclei were predominant in the low ND cases (P = 0.027). The nuclei were eccentrically located in 12 of the high ND cases but were centrally located in 14 of the low ND cases (P = 0.01). CONCLUSIONS: Mucinous carcinoma with high ND may be diagnosed by the presence of discohesiveness, a flat, monolayered pattern, and round or eccentrically located nuclei. Features of ND in carcinomas in other organs, such as intracytoplasmic granules and coarse chromatin, may not be reliable cytological features of ND in MCA.

Encephalitis caused by human herpesvirus-6B in pancreas-after-kidney transplantation.

Human herpesvirus-6 (HHV-6) is a common pathogen among children, classically presenting with fever and rash that resolves without specific therapy. HHV-6 can be reactivated in the immunosuppressed patient. After bone marrow and solid organ transplantation, HHV-6 has been linked to various clinical syndromes, including undifferentiated febrile illness, encephalitis, myelitis, hepatitis, pneumonitis, and bone marrow suppression. However, HHV-6 encephalitis after pancreatic transplant has rarely been reported. Early diagnosis and treatment of HHV-6 encephalitis may be important for affected patients. We report the case of a 53-year-old pancreas-after-kidney transplant recipient who initially presented with high fever and confusion 3 weeks after operation. We managed to save the patient's life and preserve the pancreas graft function. We also review previously reported cases of HHV-6B encephalitis in solid organ transplant recipients.

Pharmacokinetics of everolimus when combined with cyclosporine in Japanese de novo renal transplant recipients.

BACKGROUND: Currently, there are no published data on pharmacokinetics (PK) of everolimus in combination with cyclosporine in Japanese renal transplant patients. We evaluated the PK of everolimus in Japanese de novo renal transplant patients who received everolimus in combination with cyclosporine. METHODS: In this phase 3, multicenter, randomized, open-label study, patients were randomized (1:1) to 1 of the 2 groups: everolimus 1.5 mg (targeted C0 of 3-8 ng/mL) plus reduced-dose cyclosporine or mycophenolate mofetil 2 g/d plus standard-dose cyclosporine. PK assessments for everolimus were performed on day 28 (month 1) in the PK subpopulation. RESULTS: A total of 11 patients (7 men), mean age 47.5 ± 11.21 years, were enrolled for PK analysis of everolimus. Starting at 1.5 mg (0.75 mg twice a day), the mean dose over a period of 28 days was 0.705 ± 0.1011 mg. Everolimus mean trough concentration was 4.307 ± 1.2459 ng/mL and mean peak concentration was 13.539 ± 3.5330 ng/mL, which peaked at 1 to 2 hours postdose. The average concentration was 7.558 ± 1.4723 ng/mL, area under the concentration-time curve was 90.70 ± 17.667 ng·h/mL, and peak-trough fluctuation was 122.6%. The PK parameters of everolimus were comparable to those in the earlier phase 3 studies (A2306 and A2307). The mean everolimus trough levels were within the target ranges at all time points ranging from 3.4 to 5.5 ng/mL (everolimus 0.75 mg twice a day, safety population). The majority of patients (>85% from day 7 onward) were maintained within the targeted everolimus trough blood levels (safety population). These data were similar to a non-Japanese study (A2309). CONCLUSIONS: The pharmacokinetic characteristics of everolimus in Japanese de novo renal transplant patients did not differ from those previously observed in non-Japanese patients, hence the same dosage of everolimus may be acceptable in Japanese patients.

Acute antibody-mediated rejection possibly due to anti-human leukocyte antigen DQB1 antibodies after renal transplantation - case report.

A 61-year-old Japanese woman, who had undergone hemodialysis because of chronic glomerulonephritis, received a living renal transplant from her ABO blood type-compatible spouse. HLA typing of A, B and DRB showed 3/6 mismatches. Complement-dependent cytotoxicity crossmatches, HLA antibody screening with the use of flow panel reactive antibody (PRA), and flow cytometry crossmatches (FCXM) were all negative. Tacrolimus, mycophenolate mofetil, methylprednisolone (MP), and basiliximab induction were used as the standard immunosuppressive therapy. After renal transplantation, her serum creatinine level favorably decreased, but urine output was not sufficiently obtained, contrary to our expectations. Doppler sonography revealed disappearance of diastolic arterial flow on postoperative day 2. The episode biopsy showed acute antibody-mediated rejection (AMR) based on the current Banff classification, although FCXM and flow PRA were still negative. To determine the cause of acute AMR, we expanded the HLA typing at high resolution levels to Cw, DQB1, and DPB1. Retrospective analysis of perioperative sera demonstrated the presence of low levels of donor-specific HLA IgG and moderate levels of IgM antibody against DQB1 before transplantation. There was an elevation of IgM antibody at the time of rejection, whereas IgG antibody showed no remarkable change. AMR was successfully treated with plasma exchange, low-dose intravenous immunoglobulin, high-dose intravenous MP pulse, and rituximab.

Potent immunosuppression for ABO-incompatible renal transplantation may not be a risk factor for malignancy.

ABO-incompatible (ABOi) renal transplantation has been increasing, but malignant tumor is a troubling complication of kidney transplantation due to potent immunosuppression. Few previous studies, however, have demonstrated that potent immunosuppression for ABOi living-donor renal transplantation (LDRT) is a risk factor for malignancy. In the present research, data on 252 LDRT patients ftom 2003 to 2008 were retrospectively analyzed to clarify whether ABOi LDRT was associated with malignancy. A potent immunosuppressive regimen for ABOiLDRT consisted of splenectomy, cyclophosphamide, and double-filtration plasmapheresis to minimize the risk of antibody-mediated rejection, in addition to conventional immunosuppresssants including calcineurin inhibitor, prednisolone, and anti-CD25 monoclonal antibody. A total of 11 incidences of malignancy were observed during a median follow-up of 48 months. The incidence rates in ABO-compatible (ABOc; n = 189) and ABOi (n = 63) LDRT groups were 4.2 % (8/189) and 4.8 % (3/63), respectively. Kaplan-Meier survival analysis showed no statistical difference in event-free survival for malignancy between ABOc and ABOiLDRT groups (log-rank P = .73). Multivariable Cox regression analyses identified no associations of malignancy with ABOi LDRT or any immunosuppressant use. In conclusion, our investigation suggested that potent immunosuppression with splenectomy and cyclophosphamide for ABOi LDRT may not be a risk factor for malignancy.

Clinical characteristics and outcomes of renal transplantation in elderly recipients.

BACKGROUND: Elderly renal transplant candidates constitute one the fastest-growing populations among end-stage renal disease patients. Since the impacts of advanced recipient age have not yet been fully defined, we evaluated the clinical characteristics and outcomes of elderly renal transplant recipients. METHODS: Among 564 adult renal transplant recipients, at our center between 2000 and 2009, 64 were at least 60 years of age (Elderly group), and 500 were younger than 60 years (Young group) at the time of the procedure. We compared their clinical features and surgical management. RESULTS: There were significant differences in mean donor age (55.6 years vs. 53.2 years, P = .030) and gender mismatch (77.0% vs. 63.4%, P = .035). However, there were no significant differences between the two groups in patient and graft survivals (P = .177 and P = .365, respectively). Malignancy after transplantation was a significant risk factor upon univariate evaluation but only ABO incompatibility upon multivariate analysis of patient and graft survival. The main cause of graft loss among the Elderly group was death with a functioning graft due to heart failure. CONCLUSIONS: Renal transplantation is a feasible, safe option for the elderly and should be actively implemented. However, screening for cancer and heart disease should be mandatory to improve outcomes.

Pharmacokinetics and pharmacodynamics of basiliximab in Japanese pediatric renal transplant patients.

OBJECTIVES: This study was aimed at evaluating the pharmacokinetics and pharmacodynamics of basiliximab in Japanese pediatric renal transplant patients. MATERIALS AND METHODS: This study was carried out with the approval of the Institutional Review Board of our institution. Written consent was obtained from the legal representative of each patient, as also from the patients themselves where possible. Eligible patients were Japanese pediatric patients weighing less than 35 kg and younger than 15 years of age who were scheduled to undergo renal transplantation. Each patient was given intravenous basiliximab at the total dose of 20 mg administered in two divided doses of 10 mg each on the day of transplantation and on the fourth day after transplantation. Cyclosporine and corticosteroids were also administered as the basic concomitant maintenance immunosuppressive therapy. The time course of changes in the serum basiliximab concentrations and the percentage of CD25+ T-lymphocytes in the peripheral blood were determined up to 26 weeks after the transplantation to calculate the period of suppression of the CD25+ T-lymphocytes. Serum basiliximab was measured by an ELISA technique, and the percentage of CD25+ T-lymphocytes in the peripheral blood was determined by flow cytometry. RESULTS: 6 Japanese pediatric patients weighing less than 35 kg and aged over 1 year and less than 15 years who were scheduled to undergo renal transplantation were enrolled in this study. In regard to the time course of changes of the serum basiliximab concentration, after the peak serum concentration was reached, basiliximab was gradually eliminated from the blood with a mean half-life of 7.06 days. CD25+ T-lymphocytes in the peripheral blood were suppressed completely when the serum concentration of basiliximab was over 0.2 microg/ml, and the period of suppression of the CD25+ T cells was 40.3 - 51.7 days (mean +/- SD; 45.8 +/- 4.9). CONCLUSION: Changes in the serum concentration of basiliximab and the period of suppression of CD25+ peripheral blood T-lymphocytes in Japanese pediatric renal transplant patients were similar to those reported for non-Japanese pediatric transplant patients and Japanese adult renal transplant patients with a cyclosporine and corticosteroid regimen. This indicates that expected efficacy can be obtained in Japanese pediatric renal transplant patients using the recommended dosing regimens validated by non-Japanese studies.

Pretransplant pharmacodynamic analysis of immunosuppressive agents using CFSE-based T-cell proliferation assay.

The impact of pretransplant T-cell sensitivity testing using carboxylfluorescein diacetate succinimidyl ester (CFSE)-based flow cytometry was studied in 32 patients with chronic renal failure. There was considerable interindividual variation in the inhibitory effects of cyclosporine (CSA), tacrolimus (TAC), and prednisolone (PRD) but only a small amount of interindividual variation for mycophenolic acid (MPA). Patients with high sensitivity to CSA tended to experience viral reactivation. In addition to post-transplant blood-level monitoring, pretransplant pharmacodynamics could provide useful information on optimal and safe immunosuppressive therapy.

A survey on the prevalence and management of hepatitis B after renal transplantation in Asian-Pacific countries.

The carrier rate for hepatitis B virus (HBV) varies from 1% to 2% to 10% in Asian-Pacific countries. A survey involving 12 transplant centers from 11 countries in this region showed that 1% to 25% of kidney transplant recipients were infected with HBV, and up to 60% of these subjects showed abnormal liver biochemistry. While nearly all centers tested anti-HBs in potential kidney transplant recipients, HBV vaccination of nonimmune subjects was routine in only 66.7%. One-third of the surveyed units rejected HBsAg-positive subjects as kidney donors, while the others demonstrated differing policies in choosing the respective recipients. Two units (16.7%) excluded HBsAg-positive patients from kidney transplantation, whereas the others only excluded those with severe liver disease. Heterogeneity also applies to the immunosuppressive regimens, the use of HBV DNA in serial monitoring, and the timing of antiviral therapy in HBsAg-positive kidney transplant recipients. The data showed that despite HBV infection being a significant problem in kidney transplantation, there is a lack of uniform management policy, attributable to the clinical complexity and deficiency of research data. Although improvement in clinical outcome is likely with the advent of nucleoside analogue therapy and better monitoring, the financial implications in the adoption of these recent advances remain realistic concerns.

Effect of tacrolimus and cyclosporine on renal microcirculation and nitric oxide production.

OBJECTIVES: Cyclosporine (CSA) and tacrolimus (TAC) frequently induce nephrotoxicity and similar pathologic changes. Acute CSA-induced nephrotoxicity has been reported to be mediated by activation of vasoconstrictors such as endothelin. The purpose of the present study was to investigate the acute effects of TAC and CSA on the renal microcirculation and upon a vasodilator such as nitric oxide (NO) production. METHODS: Renal blood flow (RBF) in the microcirculation was measured by a Laser Doppler flow meter in uninephrectomised rats. RBF, mean arterial pressure (MAP), and renal vascular resistance (RVR) were measured in the following groups: (a) TAC (0.1 to 2.0 mg/kg/h, n = 3 approximately 6); CSA (20 and 50 mg/kg/h, n = 5); (b) L-NAME (10 mg/kg), an NO synthase inhibitor, 8 minutes prior to TAC (0.5 and 1.5 mg/kg/h, n = 5), or CSA (20 and 50 mg/kg/h, n = 5). Stable NO end-products, serum NO(2) and NO(3), were measured by the Griess method (n = 5). RESULTS: None of the parameters were changed by TAC alone, whereas TAC with L-NAME significantly reduced RBF (-28 +/- 7%) and increased RVR (46 +/- 17%) in a dose-dependent manner. CSA alone significantly reduced RBF (-37 +/- 6%) and increased RVR (69 +/- 22%) without any changes in MAP. The effects of CSA were enhanced by L-NAME. Serum concentration of NO(2) + NO(3) was significantly reduced by both L-NAME alone and CSA (50 mg/kg) (P < .05), while there were no changes with TAC (1.5 mg/kg). CONCLUSIONS: Blockade of NO production enhance the vasoconstrictive effect of CSA, and unmasked such an effect of TAC. These results suggest that the nephrotoxicity of CSA and TAC may involve the NO system.

Intravenous digital subtraction angiography and helical computed tomography in evaluation of living renal donors.

OBJECTIVES: The present study was carried out to evaluate the accuracy of helical computed tomography (CT) and intravenous digital subtraction angiography (IV-DSA) on anatomical assessment of renal vasculature for living renal donors. METHODS: Forty-two healthy potential renal donors were prospectively evaluated and 35 subsequently underwent donor nephrectomy after helical CT and IV-DSA evaluation. The vascular and non-vascular findings were compared between the findings on helical CT, IV-DSA and surgery. RESULTS: Ten prehilar branches and five accessory renal arteries were found at nephrectomy. Overall, operative findings agreed with the findings by IV-DSA in 89% and by helical CT in 83%. In delineating accessory arteries, IV-DSA had a sensitivity of 60% and specificity of 97%, whereas helical CT had a sensitivity of 40% and specificity of 100%. In delineating prehilar branches, IV-DSA had a sensitivity of 90% and specificity of 100%, whereas helical CT had a sensitivity of 70% and specificity of 100%. Accessory arteries and prehilar branches that were not detected by helical CT or IV-DSA, were less than 2 mm in diameter and did not require vascular reconstruction. Renal veins were delineated in 63% by IV-DSA, whereas they were clearly imaged by helical CT in all cases, including a case with a circumaortic renal vein. Non-vascular findings were obtained in 64% by helical CT, including two renal tumors. None of these findings were obtained by IV-DSA. CONCLUSION: Helical CT and IV-DSA provide comparably sufficient information on renal artery vasculature. However, helical CT provides significantly more information on venous and non-vascular findings as a single-imaging modality.

Laparsocopic ureteroureterostomy for retrocaval ureter.

Two cases of retrocaval ureter are reported that were successfully treated by a laparoscopic approach. Case 1 was a 20-year-old woman who presented with symptoms of a right ureter stone. Case 2 was a 23-year-old woman who had suffered from recurrent right flank pain with gross hematuria. A transperitoneal approach was used for case 1, and a retroperitoneal approach was used in case 2. Both were successfully treated with laparoscopic ureteroureterostomy using an intracorporeal suture technique. Laparoscopic surgery should be the first choice for retrocaval ureter not only because of the minimal invasiveness but also because of the cosmetic advantage compared to conventional open surgery. Further technical and instrumental advances are essential for intracorporeal suturing.

Pre-emptive renal transplantation in children.

BACKGROUND: Renal transplantation is a definitive therapeutic modality in end-stage renal disease (ESRD). Most ESRD patients in Japan experience dialysis prior to renal transplantation. The present study was undertaken to examine the usefulness of pre-emptive renal transplantation (PET). METHODS: Between 1987 and 1998, 255 renal transplantations were carried out by the authors. Among those consecutive cases, 10 were cases of PET. In nine pediatric cases, demographics, graft and patient survival, height growth and benefits from successful transplantation were studied and compared with age-matched dialyzed transplantation controls. RESULTS: All transplantation was living-related. There was a disparity of causes of ESRD between the two groups. In PET, acquired renal deterioration due to a congenital lower urinary tract disorder was the major cause. Graft and patient prognosis was favorable in both groups. Growth retardation in PET patients under 15 years of age was significantly less apparent at the time of transplantation and after 3 years compared to the control. The benefits from transplantation were different in the two groups. Most PET patients felt an improvement of their physical condition; however, all of the control patients felt that the major boon was the freedom from the restriction of the daily diet and time for dialysis. CONCLUSION: In pediatric renal transplantation, short-term preceding dialysis does not have a detrimental effect, but PET could benefit ESRD patients by maintaining their quality of life. Moreover, PET minimizes the production of renal dwarfism in prepubertal children. Thus, PET should be taken into consideration in the choice of renal replacement therapy.

Comparison of urine cytology between the ileal conduit and Indiana pouch.

OBJECTIVE: To compare the cytomorphologic features of urine obtained from two different kinds of urinary diversions constructed after total bladder resection. STUDY DESIGN: The smears of urine from 11 ileal conduits and 6 Indiana pouches were evaluated. All patients underwent total bladder resection due to transitional cell carcinoma (TCC) or other kinds of cancer before urine diversion. RESULTS: The cytologic features of Indiana pouch urine include degenerated, small, round cells without columnar cells derived from intestinal epithelium. In ileal conduit urine, well-preserved columnar cells and degenerated, small, round cells were frequently observed. The columnar cells in ileal conduit urine exhibited cytologic features that should be distinguished from TCC cells. CONCLUSION: The method of reconstructing the urinary tract is important in urine cytology from urine diversions because the cytomorphologic features of urine are different between the two kinds of urinary diversions. Since columnar cells in ileal conduit urine might lead to misdiagnosis as TCC, special consideration is required to examine ileal conduit urine.

Endothelin A receptor antagonist reduces renal vasoconstriction induced by mechanical manipulation of renal artery.

The purpose of this study was to make a model of renal vasoconstriction induced by mechanical manipulation of the renal artery and to investigate the influence of endothelin (ET) in renal vasoconstriction. Renal arteries of anesthetized rats were stretched with a 30-gram weight for 5 min, and released. Renal blood flow (RBF) was monitored with a laser flowmeter. To determine the role of ET, a selective ET(A) receptor antagonist, BQ-123 (0.1 and 1 mg/kg) was administered into the aorta. The manipulation was invariably followed by a flow reduction of about 57% after temporary hyperemia. RBF returned to the basal level 5 min after the release. BQ-123 partially, but significantly, inhibited the mechanical manipulation-induced reduction of RBF in a dose-dependent manner. These results suggest that endogeneous ET may play an important role in renal vasoconstriction induced by mechanical manipulation of the renal artery.

Intraallograft chemokine RNA and protein during rejection of MHC-matched/multiple minor histocompatibility-disparate skin grafts.

Chemokines direct leukocyte recruitment into sites of tissue inflammation and may facilitate recruitment of leukocytes into allografts following transplantation. Although the expression of chemokines during rejection of MHC-disparate allografts has been examined, chemokine expression in MHC-matched/multiple minor histocompatibility Ag-disparate allografts has not been tested. The intraallograft RNA expression of several C-X-C and C-C chemokines was tested during rejection of full thickness skin grafts from B10. D2 donors on control Ig-, anti-CD4 mAb-, and anti-CD8 mAb-treated BALB/c recipients. In all recipients, two patterns of intragraft chemokine expression were observed during rejection of these grafts: 1) macrophage-inflammatory protein-1alpha, macrophage-inflammatory protein-1beta, GRO-alpha (KC), JE, and IFN-gamma-inducible protein (IP-10) were expressed at equivalent levels in allo- and isografts for 2-4 days posttransplant and then returned to low or undetectable levels; and 2) IP-10 and monokine induced by IFN-gamma (Mig) were expressed in the allografts 3 days before rejection was completed, suggesting a possible role in recruiting primed T cells into the allograft. Three days before completion of rejection, intraallograft IP-10 protein was restricted to the epidermis, whereas Mig was located in the lower dermis and associated with the intense infiltration of mononuclear cells. Treatment of B10.D2 recipients with rabbit antiserum to Mig, but not to IP-10, delayed rejection of the allografts 3-4 days. The results suggest that Mig mediates optimal recruitment of T cells into MHC-matched/multiple minor histocompatibility Ag-disparate allografts during rejection.