Atsushi Fukuzaki

Melanocyte-specific Microphthalmia-associated Transcription Factor Isoform Activates Its Own Gene Promoter through Physical Interaction with Lymphoid-enhancing Factor 1

Waardenburg syndrome type 2 (WS2) is associated with heterozygous mutations in the gene encoding microphthalmia-associated transcription factor (MITF) and characterized by deafness and hypopigmentation due to lack of melanocytes in the inner ear and skin. Melanocyte-specific MITF isoform (MITF-M) is essential for melanocyte differentiation and is transcriptionally induced by Wnt signaling that is mediated by β-catenin and LEF-1. Here we show that MITF-M transactivates its own promoter (Mpromoter) by interacting with LEF-1, as judged by transient expression assays and in vitro protein-protein binding assays, whereas no transactivation of the M promoter was detected with MITF-M alone or with the combination of MITF-M and dominant-negative LEF1 that lacks the β-catenin-binding domain. This synergy depends on the three LEF-1-binding sites that are clustered in the proximalM promoter. Importantly, MITF-M recruited on the M promoter could function as a non-DNA-binding cofactor for LEF-1. Thus, MITF-M may function as a self-regulator of its own expression to maintain a threshold level of MITF-M that is required for melanocyte development. We suggest that MITF-M haploinsufficiency may impair the dosage-sensitive role of MITF-M or the correct assembly of multiple transcription factors, involving MITF-M, on the Mpromoter, which could account for dominant inheritance of WS2.

Gamma-knife radiosurgery for brain metastasis of renal cell carcinoma: Results in 42 patients

Background: The present study provides data from clinical experience with gamma‐knife radiosurgery (GK) in patients with brain metastasis from renal cell carcinoma (RCC) and shows the value of this less invasive treatment modality.

Risk factors in past histories and familial episodes related to development of testicular germ cell tumor.

Abstract  Background:  A retrospective study was conducted to examine the host factors of 240 testicular germ cell tumor patients. This study was performed to address a new theory proposed by Skakkebaek called testicular dysgenesis syndrome which claims that cryptorchism, hypospadias, poor semen quality and testicular germ cell tumors are symptoms of an underlying testicular dysgenesis in uterus.

Role of protein kinase C in cisplatin nephrotoxicity

Background: Cisplatin is widely used in cancer treatment. The major disadvantage of this antitumor agent is its nephrotoxicity. The mechanism of cisplatin‐induced nephrotoxicity has not been clarified. Recent evidence suggests protein kinase C (PKC)‐related signal transduction pathways may modulate cisplatin‐induced cytotoxicity.

Role of leukocyte adhesion molecules in monocyte/ macrophage infiltration in weanling rats with unilateral ureteral obstruction.

Abstract Background Unilateral ureteral obstruction (UUO) of rats is a well‐established model for studying obstructive nephropathy. Meanwhile, pathophysiology of pediatric obstructive nephropathy is not well understood. In this report, we studied monocyte/macrophage infiltration and expression of intercellular adhesion molecule 1 (ICAM‐1) and macrophage antigen 1 (Mac‐1) in weanling rats with UUO.

Complete regression of bone metastases on super bone scan, by low-dose cisplatin, UFT, diethylstilbestrol diphosphate, and dexamethasone in a patient with hormone-refractory prostate cancer

Abstract. Many types of chemotherapy are now being attempted all over the world for hormone-refractory prostate cancer (HRPC) patients, and prostate-specific antigen (PSA) reduction in almost half of the treated patients has been reported. However, only a few studies have reported the response of bone metastasis. The authors report a patient with HRPC who obtained complete regression of bone metastases on super bone scan by biochemical modulation (BM), dexamethasone, and endocrine therapy.

Plasminogen activator inhibitor-1 and tissue-type plasminogen activator are up-regulated during unilateral ureteral obstruction in adult rats.

PURPOSE The plasminogen activator (PA)-plasmin system has been shown to influence turnover of the extracellular matrix in various tissues. We examined the alteration of plasminogen activator inhibitor-1 (PAI-1) and tissue-type plasminogen activator (t-PA) in kidneys with unilateral ureteral obstruction in rats. MATERIALS AND METHODS Female rats that underwent ligation of the left ureter were sacrificed 12 hours, 1, 5 or 10 days later. The expressions of PAI-1 and t-PA was determined by reverse transcription-polymerase chain reaction and immunohistochemical studies in the obstructed and contralateral kidneys in each group. RESULTS Control kidneys showed no PAI-1 messenger (m)RNA expression. After days 1 through 10 of unilateral ureteral obstruction the amount of PAI-1 mRNA significantly increased in obstructed compared with contralateral kidneys (p <0.01). Meanwhile, slight polymerase chain reaction products of t-PA were observed in control kidneys. After 12 hours through 10 days of unilateral ureteral obstruction, t-PA mRNA in obstructed and contralateral kidneys was significantly elevated compared with in control kidneys (p <0.05). No significant difference in t-PA was observed in the obstructed and contralateral kidneys in each group. Immunoreactivity to PAI-1 and t-PA was identified in obstructed kidneys. CONCLUSIONS PAI-1 and t-PA are up-regulated in obstructed rat kidneys. Our results indicate that the PA-plasmin system has a role in the process of matrix accumulation and degradation during rat obstructive nephropathy.

Chronic Unilateral Ureteral Obstruction Represented as Renin-Dependent Hypertension

A 50-year-old woman developed renin-dependent hypertension immediately after accidental unilateral ureteral ligation during hysterectomy, and the hypertension lasted for 5 months. Surgical release of the obstruction was carried out 157 days after the ligation. Then, her blood pressure was normalized. However, the obstructed kidney showed intensive tubulointerstitial fibrosis and functional recovery was not obtained. This case suggests that the renin-angiotensin system may be upregulated in human kidney during unilateral ureteral obstruction for a long duration.

Determining the Origin of Hematuria by Immunocytochemical Staining of Erythrocytes in Urine for Tamm-Horsfall Protein

PURPOSE We analyzed the feasibility of immunocytochemical staining of urinary erythrocytes for Tamm-Horsfall protein to differentiate renal from nonrenal hematuria. MATERIALS AND METHODS Urine samples collected from 74 patients with hematuria were evaluated. Erythrocytes in urine were inspected morphologically and the same samples were immunocytochemically stained with antibody against human Tamm-Horsfall protein. RESULTS Erythrocytes in urine were clearly stained for Tamm-Horsfall protein in renal hematuria. Tamm-Horsfall protein immunocytochemistry was more consistent with clinical diagnosis than morphology. CONCLUSIONS Immunocytochemical staining of urine erythrocytes for Tamm-Horsfall protein appears to be a reliable tool to differentiate renal from nonrenal hematuria.

Characterization of G Proteins in Obstructed Kidneys

Background: Urinary tract obstruction has a marked effect on renal function. Activation of phospholipases which results in incremental production of vasoactive eicosanoids may contribute to the hemodynamic changes characteristic of an obstructed kidney. G proteins play an important role in transmembrane signal transduction, which controls phospholipase activities and eicosanoid production. The present study was designed to determine the presence of G proteins in obstructed kidneys in rats, and to characterize the differences between unilateral ureteral obstruction (UUO) and bilateral ureteral obstruction (BUO).