Disease-specific expression of VEGF and its receptors in AML cells: possible autocrine pathway of VEGF/type1 receptor of VEGF in t(15;17) AML and VEGF/type2 receptor of VEGF in t(8;21) AML.

Various angiogenic factors, such as vascular endothelial growth factor (VEGF) and an associated molecule, placenta growth factor (PlGF), are thought to be important for normal and malignant hematopoiesis. This study examined mRNA expression of VEGF, PlGF and receptors for these molecules in AML cells and identified the disease-specific patterns of expression. AML M3 having t(15;17) abnormality showed highest expression of VEGF and VEGF receptor type 1 (VEGFR1), suggesting the autocrine pathway of VEGF-VEGFR1. Then, t(8;21) AML demonstrated augmented expression of VEGF and VEGF receptor type 2 (VEGFR2), suggesting VEGF-VEGFR2 autocrine pathway. Then, addition of VEGFR2 kinase inhibitor in Kasumi-1, a t(8;21) AML cell line, resulted in marked inhibition of cell growth, although growth inhibitory effect of R2 kinase inhibitor to HL-60 was marginal. In addition, cell cycle analysis study showed S-phase cell population reduction by R2 kinase inhibitor in Kasumi-1, but not in HL-60. This observation is thought to be the rationale for novel molecular target therapy directed to angiogenic molecules.

Multiple myeloma oncogene 1 (MUM1)/interferon regulatory factor 4 (IRF4) upregulates monokine induced by interferon-gamma (MIG) gene expression in B-cell malignancy.

MUM1 (multiple myeloma oncogene 1)/IRF4 (interferon regulatory factor 4) is a transcription factor that is activated as a result of t(6;14)(p25;q32) in multiple myeloma. MUM1 expression is seen in various B-cell lymphomas and predicts an unfavorable outcome in some lymphoma subtypes. To elucidate its role in B-cell malignancies, we prepared MUM1-expressing Ba/F3 cells, which proliferated until higher cellular density than the parental cells, and performed cDNA microarray analysis to identify genes whose expression is regulated by MUM1. We found that the expression of four genes including FK506-binding protein 3 (FKBP3), the monokine induced by interferon-gamma(MIG), Fas apoptotic inhibitory molecule (Faim) and Zinc-finger protein 94 was altered in the MUM1-expressing cells. We then focused on MIG since its expression was immediately upregulated by MUM1. In reporter assays, MUM1 activated the MIG promoter in cooperation with PU.1, and the interaction between MUM1 and the MIG promoter sequence was confirmed. The expression of MIG was correlated with that of MUM1 in B-CLL cell lines, and treatment with neutralizing antibodies against MIG and its receptor, CXCR3, slightly inhibited the proliferation of two MUM1-expressing lines. These results suggest that MUM1 plays roles in the progression of B-cell lymphoma/leukemia by regulating the expression of various genes including MIG. Leukemia (2005) 19, 1471-1478. doi:10.1038/sj.leu.2403833; published online 16 June 2005.

Reversibility from delayed hyperacute rejection in ABO-incompatible renal transplantation: histopathological findings of renal allograft biopsy.

ABO-incompatible renal transplantation (ABOIRTx) tend to lead to blood type antibody-mediated rejection, the so-called delayed hyperacute rejection (DHAR), which results in short-term graft loss. To clarify the accurate incidence and prognostic value of DHAR among ABOIRTx, we reviewed biopsy specimens obtained from ABOKTx allografts with abrupt dysfunction during the early period after transplantation. Among 74 ABOIRTx patients, 34 patients displayed allograft dysfunction within 14 days following transplantation. The biopsy specimens were classified based on the Banff schema. The pathological diagnosis of ABO blood type antibody-mediated humoral rejection (ABO-AMHR) was made by the following 3 findings: Specimens with all of above-mentioned findings were categorized as severe ABO-AMHR; those with at least one findings, were categorized as mild ABO-AMHR. All patients were treated with steroid pulse therapy and/or modification of other immunosuppressants. Group 1 consisted of severe ABO-AMHR (n = 6); group 2 consisted of mild ABO-AMHR (n = 5); group 3 consisted of acute cellular rejection (n = 3); group 4 consisted of recovery phase of ATN (n = 11); group 5 consisted of calcineurin inhibitor toxicity (n = 2); and group 6 consisted of normal histology (n = 5). One of 6 patients (16%) in group 1 lost the graft because of DHAR irreversible by antirejection and anticoagulation therapy. However, there has been no clear definition of histpathological criteria for DHAR after ABO-incompatible kidney transplantation. The definition must prognosticate whether the rejection process is reversible.

ABO-incompatible living-donor kidney transplantation in children.

BACKGROUND: Due to a severe shortage of suitable cadaveric allografts for children awaiting kidney transplants, we have performed a series of ABO-incompatible living kidney transplantations (LKT) at our institution. METHODS: Between July 1989 and March 2000, 16 pediatric patients (3 female, 13 male) underwent ABO-incompatible LKT. The mean age at transplantation was 10.9+/-4.3 years (range 5.1-15.0 years). The donor to recipient ABO blood antigen incompatibility was as follows: A1-->O, 5 patients; B-->O, 6 patients; A1B-->B, 2 patients; and A1B -->B, A1-->B, or B-->A1, 1 patient each. The median pretransplantation anti-A1 titers of eight A-incompatible recipients were 1:128 (IgM, range 1:16 to 1:512) and 1:32 (IgG, range 1:2 to 1:128). Median anti-B titers of seven B-incompatible recipients were 1:32 (IgM, range 1:4 to 1:128) and 1:8 (IgG, range 1:2 to 1:64). All patients received three or four sessions of plasmapheresis (PP) and/or immunoadsorption (IA) to remove the anti-A and/or anti-B antibodies before transplantation. Immunosuppression initially consisted of cyclosporine, methylprednisolone, cyclophosphamide, and antilymphocyte globulin. Splenectomy was performed on all recipients at the time of transplantation. RESULTS: The patients were followed for 6 to 122 months with a mean follow-up of 63 months. All 16 recipients who underwent ABO-incompatible LKT achieved a pretransplant isoagglutinin titer less than 1:8 with 3-4 sessions of PP/IA treatment. Of 16 patients, 10 patients had rebound increase in their IgM and/or IgG anti-A/B titers to greater than 1:64 or predepletion levels within 10 days posttransplantation. In addition, nine patients developed renal dysfunction in association with the rebound increase in their anti-A/B. One patient lost his graft because of uncontrolled delayed hyperacute rejection, whereas eight other recipients recovered completely with pulse steroids and PP/IA therapy. After the third week posttransplant, there was no correlation between the occurrence of AR and their isoagglutinin titers. Moreover, no antibody-mediated rejection was observed, even in recipients with continued high titer anti-A and/or anti-B antibodies. Patient survival is 100% to date. The actuarial 1-year and 5-year graft survival rates are 87% and 85%, respectively. No fatal infectious complications occurred despite the combination of splenectomy and immunosuppressive drugs. CONCLUSIONS: We have demonstrated that with adequate pre- and posttransplant management, successful kidney transplantation across the ABO barrier is possible in the pediatric population. "Accommodation" of the allografts occurred within 2 weeks of transplantation. Subsequently, the long-term graft outcome of ABO-incompatible LKT was comparable to that of ABO-compatible LKT.

The relative importance of wife abuse as a risk factor for violence against children.

OBJECTIVE: To investigate the relative importance of wife abuse as a risk factor for physical child abuse, physical punishment, and verbal child abuse. The study explored the importance of wife abuse relative to blocks of parent, child, and family characteristics and also relative to specific risk factors. METHOD: This study re-analyzed a sub-sample (N = 2,733) of data from the 1985 National Family Violence Survey. Hierarchical logistic regressions were conducted, using five different criterion variables measuring physical child abuse, physical punishment, and verbal abuse separately and in combination. RESULTS: Blocks of parent, child, and family characteristics were more important predictors of violence towards children than was wife abuse, though the presence of wife abuse in the home was a consistently significant specific risk factor for all forms of violence against children. Of specific risk factors, a respondent's history of having been hit as an adolescent was a larger risk factor for physical child abuse than was wife abuse. Wife abuse was an important predictor of physical punishment. Non-violent marital discord was a greater factor in predicting likelihood of verbal child abuse than was wife abuse. CONCLUSIONS: Though this study confirms the association between wife abuse and violence towards children, it cautions us not to overlook the contribution of other factors in our attempts to understand the increased risk attributed to wife abuse.

Congenital vesicovaginal fistula.

Congenital vesicovaginal fistula is a very rare entity, the etiology of which has not been clearly elucidated because pathologic features have not been mentioned in previous reports. The case of a 4-year-old girl having incontinence resulting from a congenital vesicovaginal fistula joining with the left ectopic ureter from the hypoplastic kidney is described. This is thought to be the first presentation of congenital vesicovaginal fistula joining with ectopic ureter. A microscopic examination revealed the fistula consisting of transitional cell epithelium, suggesting an abnormal fusion of the ureteral bud and caudal end of the müllerian duct with the urogenital sinus.

Successful transplantation of a cadaveric kidney with post-infectious glomerulonephritis.

This report describes a successful renal Tx in a patient with chronic renal failure, caused by dysplastic kidneys, who received a cadaveric kidney with post-infectious glomerulonephritis. Sequential renal biopsies were performed at 12 h before Tx, and at 1 h and on days 8 and 58 post-Tx. Post-operative hematuria disappeared on day 9 and proteinuria on day 13. Normal graft function was observed within 1 month, with histologic resolution. Our study suggests that while the donor kidney facilitates deposition of certain immune reactants, this is a host (environmental) problem and when transplanted into a new host (new environment), the problem is no longer sustained.

Inflammatory pseudotumor of the bladder in neonates.

Inflammatory pseudotumors of the bladder are rare in children. We describe a 7-day-old male neonate with inflammatory pseudotumor of the bladder. He presented with a 3-day history of macroscopic hematuria. Ultrasonography, computed tomography and cystoscopy showed an intravesical mass arising from the right lateral wall. Pathologic findings obtained by open excision revealed that the tumor had spindle-shaped cells without significant atypia infiltrating into submucosal fibrous tissue. There has been no evidence of recurrent tumor 12 months post-operatively. To our knowledge our case is the first presentation in a neonate among the reported pediatric cases.

[Refluxing megaureter in infancy--the significance of differentiation from primary high grade VUR].

BACKGROUND: Recent advance of perinatal ultrasound screening and/or physician's awareness of renal damage from recurrent pyelonephritis has brought about the increasing number of infants with primary vesicoureteral reflux (VUR) including refluxing megaureter which should be conceptually differentiated from simple high grade VUR. We evaluated the clinical outcome of infants diagnosed with refluxing megaureter. PATIENTS AND METHODS: We retrospectively reviewed the clinical records of 15 infants (17 ureters) diagnosed as refluxing megaureter (max caliber > or = 10 mm) at our institution from 1988 to 1997. We compared the clinical outcome of refluxing megaureter with that of high grade VUR. (Results) Patients were 13 boys and 2 girls. Megaureter was unilateral in 13 patients and bilateral in 2. Fourteen infants (93.3%) presented with febrile urinary tract infection (UTI). The diameter of megaureter was 10-21 mm (average: 13.6 +/- 4.0 mm) at excretory urogram. Nine of 15 infants (60.0%) had breakthrough urinary infection. Its incidence was significantly higher than that of high grade VUR (21.3%) (p = 0.02). In 13 cases surgical treatments were performed, however 2 cases (max caliber: 16 mm, 21 mm) by Politano-Leadbetter or Paquin procedure required re-ureteroneocystostomy by Psoas-hitch procedure because of persistent reflux and recurrent UTI. On the other hand no patient required re-ureteroneocystostomy in high grade VUR. CONCLUSION: It is important to differentiate refluxing megaureter from high grade VUR due to high incidence of breakthrough UTI. Ureteral remodeling and/or Psoas-hitch procedure are strongly recommended for adequate length of submucosal tunnel in refluxing megaureter.

Renal cell carcinoma in children: experience at a single institution in Japan.

PURPOSE: We analyzed the presentation, treatment and survival of 4 children with renal cell carcinoma. MATERIALS AND METHODS: We retrospectively reviewed the pathological and hospital records of 4 Japanese children diagnosed with renal cell carcinoma at our hospital from 1970 to 1998. RESULTS: In the 1 boy and 3 girls with an average age of 8 years 7 months at diagnosis the most common presenting complaints were gross hematuria in 75% and a palpable abdominal mass in 50%. Computerized tomography revealed characteristic calcification within the tumor in 3 of the 4 patients (75%). In the remaining case the lesion had high density areas with microcalcification, as confirmed by histopathological study. In 2 patients with regional lymph node metastasis calcification was also observed in the metastatic lesions. Disease was stages I to III in 1, 1 and 2 patients, respectively. All patients underwent transabdominal nephrectomy with regional lymphadenectomy. One patient with stage I disease had multiple metastases 15 months later and died of disease 55 months postoperatively. However, the remaining 3 patients received adjuvant interferon therapy and they are without evidence of recurrence a mean of 51.3 months postoperatively. CONCLUSIONS: Calcification within the tumor and/or metastatic lesions or high density areas in the tumor on screening computerized tomography are characteristic findings suggestive of pediatric renal cell carcinoma. Adjuvant therapy with interferon may provide some benefit in select pediatric patients. Further studies of a larger number of pediatric renal cell carcinoma cases may be necessary to establish the optimal diagnostic and therapeutic regimen.