A case of Sertoli cell tumor

We report a case of Sertoli cell tumor. A 33-year-old man visited our clinic with a complaint of painless left scrotal swelling on September 29th, 2003. An elastic firm induration larger than a hen's egg in size was palpable on the surface of the left testis. Tumor markers for testicular tumor such as human chorionic gonadotropin-beta, alpha fetoprotein, and lactate dehydrogenase were not elevated. However, ultrasound showed a low echoic mass in the left testis. Therefore, we performed left high orchiectomy under the diagnosis of left testicular tumor. Its histology showed Sertoli cell tumor. Neither recurrence nor metastasis has been detected for about 8 months after the operation.     

Successful stenting for renal artery stenosis in a patient with Alagille syndrome

A 12-year-old girl with Alagille syndrome manifested severe hypertension caused by renal artery stenosis in a solitary functioning kidney. Percutaneous transluminal angioplasty (PTA) and stenting was performed, but the hypertension persisted. On the next day, acute renal failure occurred with the administration of angiotensin-converting enzyme inhibitor, and migration of the stent was confirmed by angiography. Thus, a second stent was placed with success. Since then, the hypertension has been controlled with anti-hypertensive medication, and the renal function has recovered to normal range.     

Decrease in prefrontal hemoglobin oxygenation during reaching tasks with delayed visual feedback: a near-infrared spectroscopy study

Visual feedback of hand movement is crucial to accurate reaching. Although previous studies have extensively examined spatial alteration of visual feedback (e.g., prism adaptation), temporal delay of visual feedback has been less explored. In the present study, we investigated the effect of delayed visual feedback of the moving hand in a reaching task. The prefrontal cortical activity was measured by near-infrared spectroscopy (NIRS). Twelve subjects performed reaching tasks under two conditions where visual feedback of their own hand was delayed by 200 ms (delay condition) or 0 ms (normal condition). Introducing the visual feedback delay significantly disrupted the reaching performance, although the subjects gradually adapted to the delay during the experiment. There was a clear tendency to overreach the target in the delay condition, even after the reaching movement had been practiced sufficiently in the normal condition. We observed marked oxy- and total-Hb decreases in the dorsal prefrontal area in the delay conditions. The decrease began shortly after task onset and diminished during the rest period, indicating that the decrease was task-induced. Furthermore, the oxy- and total-Hb decreases were significantly correlated with task performance--the degree of decrease was larger as the subject made more errors. We suggest that the decreases in oxy- and total-Hb at the dorsal prefrontal area are related with the visuomotor recalibration process.     

In vitro and in vivo characterization of pigment epithelial cells differentiated from primate embryonic stem cells

PURPOSE: To determine whether primate embryonic stem (ES) cell-derived pigment epithelial cells (ESPEs) have the properties and functions of retinal pigment epithelial (RPE) cells in vitro and in vivo. METHODS: Cynomolgus monkey ES cells were induced to differentiate into pigment epithelial cells by coculturing them with PA6 stromal cells in a differentiating medium. The expanded, single-layer ESPEs were examined by light and electron microscopy. The expression of standard RPE markers by the ESPEs was determined by RT-PCR, Western blot, and immunocytochemical analyses. The ESPEs were transplanted into the subretinal space of 4-week-old Royal College of Surgeons (RCS) rats, and the eyes were analyzed immunohistochemically at 8 weeks after grafting. The effect of the ESPE graft on the visual function of RCS rats was estimated by optokinetic reflex. RESULTS: The expanded ESPEs were hexagonal and contained significant amounts of pigment. The ESPEs expressed typical RPE markers: ZO-1, RPE65, CRALBP, and Mertk. They had extensive microvilli and were able to phagocytose latex beads. When transplanted into the subretinal space of RCS rats, the grafted ESPEs enhanced the survival of the host photoreceptors. The effects of the transplanted ESPEs were confirmed by histologic analyses and behavioral tests. CONCLUSIONS: The ESPEs had morphologic and physiological properties of normal RPE cells, and these findings suggest that these cells may provide an unlimited source of primate cells to be used for the study of pathogenesis, drug development, and cell-replacement therapy in eyes with retinal degenerative diseases due to primary RPE dysfunction.     

Otx2 homeobox gene induces photoreceptor-specific phenotypes in cells derived from adult iris and ciliary tissue

PURPOSE: It remains unclear which gene induction effectively generates photoreceptor-specific phenotypes from nonretinal tissues. The purpose of this study was to determine whether Crx and Otx2--homeobox genes related to photoreceptor development--can induce the generation of these phenotypes in cells derived from adult ciliary and iris tissue and in mesencephalon-derived neural stem cells. METHODS: Crx and Otx2 were transferred into adult rat ciliary- and embryonic mesencephalon-derived neurospheres and adult rat iris-derived cells with the aid of a recombinant retrovirus. The presence of photoreceptor-specific phenotypes was confirmed by immunocytochemistry and Western blot analysis. RESULTS: More than 90% of the Crx- and Otx2-transfected ciliary- and iris-derived cells exhibited rod opsin immunoreactivity, whereas few of the similarly transfected mesencephalon-derived neural stem cells expressed rod opsin. At least two additional key components of the phototransduction cascade, recoverin and Gdeltat1, were expressed by Crx- and Otx2-transfected iris-derived cells. CONCLUSIONS: Crx and Otx2 effectively induced the generation of photoreceptor-specific phenotypes from ciliary- and iris-derived cells. That both Crx and Otx2 induced phenotype generation in cells derived from iris or ciliary tissue may suggest an approach to photoreceptor cell preparation for retinal transplantation.     

Ionic interaction of [<Superscript>11</Superscript>C]-<Emphasis Type="Italic">N</Emphasis>, α-dimethylbenzylamine (DMBA) in rodent brain

The [S] enantiomer of [11C]-N,alpha-dimethylbenzylamine (DMBA) was synthesized by N-methylation of [S]-alpha-methylbenzylamine, and its biodistribution in mice was measured. [11C]-[S]-DMBA was rapidly distributed into the brain, heart and lungs, and considerable long-term retention in the brain was observed. The radioactive metabolites in the plasma were analyzed by liquid chromatography. Kinetic analysis using unmetabolized [11C]DMBA in the plasma as the input function was performed employing a simplified two-compartment model. The estimated distribution volumes (DV) of [11C]DMBA in the brain and heart were 6.05 and 3.95, respectively. The right striatum of the rat brain was lesioned with ibotenic acid 2 weeks before the tracer experiment. Both in vitro and in vivo autoragiographic studies were performed, and revealed significant reduction of the radioactivity levels in the lesioned striatum. On the other hand, the regional cerebral blood flow, as measured by [14C]iodoantipyrine, was not significantly altered in the lesioned striatum. These results indicate that the ionic binding component for DMBA exists mainly in neural cells rather than in glial cells. [11C]DMBA might be a useful radiotracer for detection of neural cell loss in the brain.     

A pharmacological study of the weekday-on/weekend-off oral UFT schedule in colorectal cancer patients

PURPOSE: The new weekday-on/weekend-off schedule for oral UFT administration consists of its administration for 5 consecutive days followed by 2 days off the drug. The intratumor 5-FU (5-fluorouracil) concentration has been reported to be correlated to the tumor response in patients treated with intravenous 5-FU. The aim of this study was to investigate the pharmacokinetics during the 2 days off the drug in cancer patients treated with the weekday-on/weekend-off schedule for oral UFT. METHODS: The subjects were 24 colorectal cancer patients. They were divided into three groups, and were all given UFT, 600 mg/day, for 5 days before surgery. Surgery was performed 2, 24, or 48 h after the final dose of UFT. The 5-FU concentrations in the serum, tumor, and in the normal mucosa were measured. RESULTS: The serum 5-FU concentrations after the final dose of UFT were: 23 +/- 12 ng/ml (mean +/- SD) at 2 h, 7 +/- 3 ng/ml at 24 h, and 6 +/- 3 ng/ml at 48 h. The intratumor 5-FU concentrations were: 113 +/- 45 ng/g at 2 h, 54 +/- 20 ng/ml at 24 h, and 54 +/- 35 ng/ml at 48 h, and the concentrations in the normal mucosa were: 36 +/- 15 ng/g (mean +/- SD) at 2 h, 17 +/- 6 ng/ml at 24 h, and 18 +/- 6 ng/ml at 48 h after the final dose. While the serum 5-FU concentration decreased to very low levels by 24 h after the final dose of UFT, the intratumor 5-FU concentrations were maintained at more than 50 ng/g at least until 48 h after the final dose. The 5-FU concentrations in the normal mucosa were maintained at about one third of the intratumor concentrations at all time points. CONCLUSION: Although the weekday-on/weekend-off schedule for UFT administration included intermittent 2-day drug-off periods, this pharmacokinetic study revealed that the 5-FU concentrations in the tumor were maintained at much higher levels than in the serum throughout these periods.     

The expression of MMP-2 and TIMP-2 in patients with primary colorectal adenocarcinoma: correlation with liver metastasis.

The expression of MMP-2 and TIMP-2 was examined immunohistochemically in a total of 36 colorectal cancer patients with synchronous liver metastasis at the time of surgery, and the serum MMP-2 and TIMP-2 levels were also measured in a total of 58 colorectal cancer patients with/without liver metastasis following primary colorectal surgical resection for serological comparison. Although MMP-2 exhibited a significant expression immunohistochemically in the primary colorectal cancer (p<0.05) and TIMP-2 in the synchronous liver metastasis (p<0.01), there was no relationship between the absence/presence of liver metastasis and serum MMP-2 and TIMP-2 levels, respectively. These results suggest that it can be considered difficult to use serum MMP-2 and TIMP-2 levels to predict the status of liver metastasis following primary resection in patients with colorectal adenocarcinoma.