NFκB2 Gene as a Novel Candidate that Epigenetically Responds to Interval Walking Training.

Physical fitness has been reported to decrease the risk of lifestyle-related diseases. The present study evaluated genome-wide methylation under the hypothesis that interval walking training (IWT) imparted beneficial effects on health, particularly by epigenetically ameliorating susceptibility to inflammation. We screened DNA from peripheral blood samples via genome-wide microarray for genes whose methylation was affected by IWT, paying special attention to promoter regions, and identified over 40 hyper- or hypo-methylated genes following IWT that were not witnessed in controls. We next selected genes in which the degree of methylation change in the promoter region was correlated with energy consumption following IWT. In this way, we found the NFκB2 gene to have increased methylation in multiple regions of its promoter sequence following participation in an exercise regimen. Next, IWT-induced NFκB2 hyper-methylation was confirmed by a quantitative PyroSequencing assessment of methylation in samples obtained from independent subjects who also underwent IWT. The increase in NFκB2 gene promoter methylation by IWT indicates that this regimen may suppress pro-inflammatory cytokines. Thus, these results provide an additional line of evidence that IWT is advantageous in promoting health from an epigenetic perspective by ameliorating susceptibility to inflammation.

[Scleral tattooing: A dangerous fashion trend]. / Tatouage scléral : une mode émergente dangereuse.

Tattooing of the glove is an old practice used 2000 years ago on the cornea to improve the appearance of unsightly corneal scars. Since 2007, tattoo artists have been performing scleral tattoos, also called "eyeball tattoos," despite the risks involved and the disapproval of health authorities and the medical community. We report the case of a 30-year-old man with bilateral black ink scleral tattoos who came to our ophthalmologic emergency service with episcleral nodules, which had appeared at the ink injection sites. The clinical course stabilized with topical anti-inflammatory treatment. Similar cases have been reported in the literature, in one of which the patient underwent surgical excision of a similar lesion. Histological analysis showed a lympho-histiocytic reaction without any signs of malignancy. To date, 20 cases of scleral tattoos have been reported in the international literature, often with severe complications. We see, on the one hand, complications related to perforating trauma, and on the other hand, acute and chronic complications inherent to the products used. Scleral tattooing is gaining popularity around the world despite significant risk exposure, including traumatic, inflammatory, immune, infectious and probably long-term neoplastic consequences. Ophthalmologists must be aware of this practice and its consequences in order to make the most appropriate therapeutic decisions.

Serum bone alkaline phosphatase isoenzyme levels in normal children and children with growth hormone (GH) deficiency: a potential marker for bone formation and response to GH therapy.

Serum bone alkaline phosphatase (B-ALP) has been considered to be a good marker for bone formation. Recently, a specific immunoradiometric assay for serum B-ALP has been developed. Using this system, we measured the serum levels of B-ALP in 363 normal children (207 males and 156 females, age 0-18 yr) and in 20 GH-deficient children (age 5-13 yr) who showed significant bone growth during GH therapy. We found the following results. 1) There were no significant circadian variations in serum B-ALP levels (coefficients of variation: 2.10-9.66%). 2) In normal children, serum B-ALP levels were high in infants and gradually declined and increased again during puberty. During the pubertal period, the highest serum B-ALP values were observed at midpuberty (stage 3 of breast and pubic hair development and 4-12 mL of testicular volume). 3) Serum B-ALP levels were significantly correlated with levels of the carboxy-terminal propeptide of type 1 procollagen (r = 0.447, P < 0.0001) and osteocalcin (r = 0.433, P < 0.0001). 4) After beginning GH therapy, serum B-ALP levels increased significantly; a 26% increase in serum B-ALP level was observed after 3 months of GH therapy. 5) The ratio between serum B-ALP level after 3 months of GH therapy and before GH therapy was positively correlated with the GH-induced improvement in the height SD score (height SD score after 1 yr of GH therapy minus that before GH therapy) and improvement in the height velocity SD score (height velocity SD score during GH therapy minus before GH therapy) (r = 0.531, P < 0.05 and r = 0.608, P < 0.01, respectively). 6) The increment of SD score in serum B-ALP level after 1 yr of GH treatment was also significantly correlated with that for bone mineral density after 1 yr of GH therapy (r = 0.663, P < 0.005). These results show that B-ALP levels are a useful marker for bone formation because B-ALP levels increased when the growth rate accelerated. Serum B-ALP is a potential predictor of the effectiveness of GH therapy, because the serum level after 3 months of GH therapy reflects the outcome of 1 yr of GH therapy.

Thermostable N-carbamoyl-D-amino acid amidohydrolase: screening, purification and characterization.

A thermostable N-carbamoyl-D-amino acid amidohydrolase was found in the cells of newly isolated bacterium. Blastobacter sp. A17p-4. The bacterium also showed D-specific hydantoinase activity. The N-carbamoyl-D-amino acid amidohydrolase activity of the cells exhibited a temperature optimum at 50-55 degrees C, and was stable up to 50 degrees C. The N-carbamoyl-D-amino acid amidohydrolase of Blastobacter sp. A17p-4 was purified to homogeneity and characterized. It has a relative molecular weight of about 120,000 and consists of three identical subunits with a relative molecular weight of about 40,000. N-Carbamoyl-D-amino acids having hydrophobic groups served as good substrates for the enzyme. It has been suggested that D-amino acid production from DL-5-substituted hydantoin involves the action of a series of enzymes involved in pyrimidine degradation, namely amide-ring opening enzyme, dihydropyrimidinase, and N-carbamoylamide hydrolyzing enzyme, beta-ureidopropionase. However, the purified enzyme did not hydrolyze beta-ureidopropionate; suggesting that the N-carbamoyl-D-amino acid amidohydrolase coexisting with D-specific hydantoinase, probably dihydropyrimidinase, in Blastobacter sp. A17p-4 is different from beta-ureidopropionase.

Peripheral nerve lengthening by controlled isolated distraction: a new animal model.

We have developed a simple and effective animal model to study the distraction neurogenesis utilizing the sciatic nerve-lengthening technique in rats. The model allows macroscopic, physiological, and histological evaluation of the distraction site. Fourteen adult Harlan Sprague Dawley rats (300-350 g) were used in this study. A 10 mm segment of the right sciatic nerve of each animal in the nerve-lengthening group was resected. Gradual nerve lengthening was performed by advancing the proximal nerve stump at a rate of 1 mm/day. The proximal stump neuroma was then resected and a direct nerve anastomosis was performed. On the left side a standard autogenous nerve-grafting procedure was performed with a 10 mm segment of sciatic nerve used as an in situ nerve graft. Three months after the second surgery, the sciatic nerves were exposed and investigated by gross observation and EMG followed by histological processing and tissue analysis. Neomicrovascularization was observed surrounding the sciatic nerve anastomosis in all five specimens of the nerve-lengthening group as compared to the more white-colored scar tissue that was observed in the nerve-grafting group. The EMG results were similar for both groups. Histological studies of the lengthened nerves showed axon morphology equivalent to the grafted nerves. This study demonstrated a clear evidence of the successful nerve regeneration within a segmental nerve gap by nerve lengthening.

Ubiquitous interleukin-1 alpha in fetal bovine serum may mislead the experimental results in vitro.

Fetal bovine sera (FBS) from several commercial suppliers were fractionated by gel filtration. Interleukin-1 (IL-1) activity was bioassayed using the IL-1-specific murine T cell line D10(N4)M. All the sera examined contained IL-1-like activity, with molecular weights (M(r)) of 30 kDa and 15-10 kDa. Under isoelectric focusing (IEF), the majority of IL-1 activity in either 30 kDa or 15-10 kDa fractions was focused into a position of pl 5. The activity recovered from either IEF or gel filtration was inhibited by either recombinant human IL-1 receptor antagonist (rhlL-1ra) or by the antibody against human IL-1 alpha. These biological and physicochemical properties strongly suggest that the active molecules were bovine IL-1 alpha and its precursor. There was no correlation between the amount of endotoxin and IL-1 activity. Quantification of the fractionated IL-1 indicated its presence in concentrations of 200-5000 pg/ml equivalent to human IL-1. However, high levels of IL-1 were not apparent in unfractionated FBS. Proliferation of T cells in the presence of FBS absorbed with protein A-Sepharose was greater than that of cells in original FBS. Therefore, the activity in FBS as a whole appeared to result from the balance between IL-1 and the inhibitory molecule(s). These results suggest that data obtained from experiments conducted in the presence of FBS may be influenced by the effect of bovine IL-1.

Long-term results of ethanol embolization of renal cell carcinoma.

This retrospective study was conducted to evaluate the long-term results of transarterial embolization with absolute ethanol (ethanol-TAE) for patients with renal cell carcinoma (RCC). Twenty-eight patients, including 15 stage IVb patients, underwent ethanol-TAE, with 12 of them followed by nephrectomy. The cumulative survival rates after 1, 3, and 5 years were 71%, 54%, and 54% in the surgical group, and 54%, 33%, and 22% in the non-surgical group. From the results, we recommend ethanol-TAE for advanced stage patients for the following reasons: first, it can be a useful alternative to nephrectomy in high-risk patients; second, ethanol-TAE can decrease the primary tumor size increasing operability; and third, local tumor control may result in longer survival.

Telemedical support using real-time ultrasonography and endoscopy images.

We developed a telecommunications apparatus (TMS-6101, NIHON KOHDEN WELLNESS CORPORATION, Tokyo, Japan) and evaluated its clinical utility as a telemedical support system. It is capable of transmitting on a real-time basis such vital signs as blood pressure, arterial O2 saturation and ECG recordings, which are measured at bedside using the Life-Mate monitor (NIHON KOHDEN WELLNESS Co.). It is also capable of transmitting moving video-camera pictures in real time. In this study we assessed its application for telemedical supports with particular emphasis on ultrasonography and endoscopy images since reports of such applications are lacking. Employing this system, several kinds of technically demanding endoscopic procedures were supported successfully under the supervision of at least one off-site specialist physician. The system proved to be a very useful medical resource, since it facilitated high quality medical care and specialist consultation at any location without those specialists traveling to the scene.

[Renal function study by 99mTc-DMSA renal scintigraphy in each treatment of staghorn calculi].

From 1976 through 1984, 94 staghorn calculi of 86 patients were treated in this department. Kidney function was assessed by Tc-DMSA renal scintigraphy consisting of renal cortical imaging and DMSA renal uptake rate, in 84 kidneys preoperatively and 43 kidneys pre- and postoperatively. There was an increase in the postoperative DMSA renal uptake in the operated kidney, in 3 out of 14 kidneys in which pyelolithotomy was performed and in one out of 10 kidneys in which nephrolithotomy was done. It was still impossible to answer the question of which mode of operation should be chosen only from consideration of kidney function study. But it was suggested by the statistical investigation that nephrectomy seemed to be selected in the case of severely decreased renal function. It was reasonable that pyelolithotomy was the best method from the point of predicting the postoperative recovery of renal function. But in the near future, advances in endoscopical stone surgery and extracorporeal procedures, might reduce the damage of the renal function caused by conventional stone surgery.

[Clinical study on efficacy of a Foley catheter coated with silver-protein in prevention of urinary tract infections].

We evaluated the clinical efficacy and safety of a Foley catheter coated with silver-protein (ProAg catheter) in the prevention of catheter-associated bacteriuria. ProAg catheter significantly reduced the incidence of extraluminal catheter-associated bacteriuria compared with usual latex Foley catheter although it did not inhibit intraluminal bacteriuria. There was no difference between ProAg catheter and latex catheter in the side effects such as urethral discharge, catheter-associated pain and allergic reaction. The ProAg catheter may be useful as an indwelling urethral catheter.

[Clinical application of MRI for urological malignancy. 3: A new trial of MRI for bladder cancer and prostatic cancer; surface coil and GD-DTPA].

We performed MRI in several recent cases of bladder cancer and prostatic cancer using a general coil or a 5-inch general purpose surface coil with or without Gd-DTPA. The surface coil improves the spacial resolution, density resolution and signal to noise ratio but reduces the field and the signal detection drops off as the depth from the surface increases. Moreover, additional time is required for patient positioning. In Gd-DTPA enhanced images of bladder cancer, the muscle layer became more distinct, and the images of tumor and bladder mucosa were enhanced, suggesting that facilitates evaluation of the extent of bladder wall invasion of the tumor. In Gd-DTPA enhanced images of prostatic cancer, the area conside to correspond to the tumor was enhanced. MRI using a surface coil and Gd-DTPA is considered to provide detailed information of bladder and prostatic cancer.

Staging and differential diagnosis of renal cell carcinoma: a comparison of magnetic resonance imaging (MRI) and computed tomography (CT).

The usefulness of magnetic resonance imaging (MRI) was compared with that of computed tomography (CT). Twenty-nine patients with renal cell carcinoma, 3 with angiomyolipomas and 1 with renal pelvic cancer, were examined by both MRI and CT. MRI and CT showed similar results in staging cases of renal cell carcinoma. However, MRI may be more sensitive in detecting the venous extension, metastatic adenopathy, and adjacent organ invasion. In predicting the involvement of perinephric fat, however, MRI is only marginally superior to CT. To demonstrate the usefulness of MRI in differentiating renal cell carcinoma from other renal tumors, the density of renal tumor and that of the psoas muscle were determined using a densitiometer, and the percent (%) contrast (the intensity of the renal tumor/the intensity of the psoas muscle X 100) was calculated. In most patients with clear cell type renal carcinoma, the % contrast value in the T1 weighted images was about 100. In the T2 weighted images, the maximum value of the % contrast value was 50 or less in most patients. In one patient with spindle cell type (sarcomatoid type) carcinoma, the % contrast value was 109 in the T1 weighted images, but was 65-85, at most, in the T2 weighted images. In patients with renal angiomyolipomas, the % contrast values were calculated exclusive of the fatty components. The % contrast value of the T1 weighted images was 50 or less in all 3 patients, and that of the T2 weighted images was 50 or more in 2 patients and 21-38 in the others.(ABSTRACT TRUNCATED AT 250 WORDS)

MRI of prostatic cancer: in vivo and in vitro MRI results compared with pathological findings.

Magnetic resonance imaging (MRI) of the prostate was accomplished in 23 patients who had prostatic cancer histologically proved by needle biopsy. Five prostates resected out of 23 patients with prostatic cancer were available for in vitro MRI. The MRI findings of the normal peripheral zone of the prostate had a high signal intensity on T2 weighted image, and the cancer nests in the peripheral zone had lower signal intensity than the normal peripheral zone. A partial or total destruction of the border line between outer zone and inner zone was observed besides than microscopic invasions. MRI also enabled us to differentiate the cancerous foci from the normal tissue at a different signal intensity of imaging in some selected cases in which the resected specimen was examined by in vitro MRI.

[Diagnosis of retroperitoneal lymph node swelling by computed tomography in advanced testicular cancer patients, with special reference to retrocrural lymph node swelling].

We tried to divide anatomically the retroperitoneal space into three areas on computed tomography, infrahilar, suprahilar and retrocrural spaces, and investigated the relationship between frequency of lymph node swelling in each space and clinical picture in 15 patients with testicular cancer of stage II or III, particularly focusing on the lymph node swelling in the retrocrural space. Lymph node swelling was found in the infrahilar space in 11 cases (73.3%), in the suprahilar space in 7 cases (46.7%) and in the retrocrural space in 6 cases (40.0%). Retrocrural or suprahilar lymph node swelling was always accompanied by suprahilar or infrahilar lymph node swelling. Most of the patients with retrocrural lymph node swelling had bulky tumors in the infrahilar level and frequently cervical lymph node swelling. Retrocrural lymph node swelling did not necessarily affect the patient's prognosis. The retrocrural lymph node seems to be a sentinel node for retroperitoneal lymph node swelling not only in the case of testicular cancer but also in the cancer of urogenital malignancies.

[Urinary tract infection caused by Corynebacterium sp.--a case report and an experimental study].

We repose of chronic cystitis associated with alkali urine, struvite stones and a subsequent vesicorectal fistula caused by Corynebacterium sp, probably Corynebacterium group D2. We also studied in vitro and in vivo stone formation caused by Corynebacterium renale isolated clinically. C. renale inoculated into normal human urine increased urine pH and formed struvite crystals after a 24-hr incubation. Bladder stones were also formed in rats experimentally infected by C. renale as well as P. mirabilis. Some urea splitting species of Corynebacterium such as C. group D2 and C. renale may play a role in the formation of human struvite stone.

[Experience with MAGPI (meatal advancement and glans plasty incorporated), modified MAGPI and Mathieu's technique of hypospadias repair as the last stage operation].

Over a 1-year period, 6 patients with retracted urethral meatus after two-stage hypospadias repair, underwent MAGPI and modified MAGPI technique. Only those cases with subcoronal lesions and without residual chordee were included in this series. Excellent cosmetic and functional results were achieved in all cases without any complication, furthermore, the operative technique is very simple. These are recommended as the operative procedures of choice for the retracted urethral meatus after hypospadias repair.

[Metastasis of renal cell carcinoma to ipsilateral adrenal residuum and contralateral adrenal gland after radical nephrectomy: a case report].

A 68-year-old woman had undergone radical nephrectomy via a transabdominal approach 4 years earlier for a 8 cm tumor located from the midportion to the upper pole of the right kidney. Pathological diagnosis was renal cell carcinoma (RCC), clear cell subtype, G2, pT2pN0M0. Four years postoperatively, followup computed tomography scan revealed masses in bilateral adrenal region (6 cm in diameter on the left side and 5 cm on the light). Bilateral adrenalectomy confirmed the diagnosis of adrenal metastases from clear cell carcinoma. It was concluded that the tumor had metastasized to the ipsilateral adrenal tissue as the residuum of the previous surgery. She has been treated by oral steroid supplementation without evidence of recurrence for 18 months.

[Sequential combination chemotherapy consisting of vincristine, peplomycin, methotrexate, cis-diamminedichloroplatinum (II), cytosine arabinoside and 5-fluorouracil, for advanced urothelial cancer].

Two VPM-CisCF chemotherapy regimens (vincristine (VCR), peplomycin (PEP), methotrexate (MTX), cis-diamminedichloroplatinum (II) (CDDP), cytosine arabinoside (Ara-C) and 5-fluorouracil (5-FU), established using human bladder cancer xenografts in nude mice were applied for advanced urothelial cancer. VPM-CisCF (I) consisted of 0.4 mg/m2 VCR on days 1 and 4, 2 mg/m2 PEP on days 1-7, 2 mg/m2 MTX on days 2, 3, 5 and 6, 20 mg/m2 CDDP on days 8, 20 mg/m2 Ara-C on days 8 and 13, and 150 mg/m2 5-FU on days 10-12. VPM-CisCF (II) consisted of 0.6 mg/m2 VCR on days 1 and 3, 3 mg/m2 PEP on days 1-4, 3 mg/m2 MTX on days 2 and 3, 35 mg/m2 CDDP on day 4, 20 mg/m2 Ara-C on days 4 and 7, and 200 mg/m2 5-FU on days 5 and 6. These doses were adjusted for each case: the above mentioned dose x [(80/(40 + Age))2 + (Karnofsky's performance status/100)2]. VPM-CisCF (I) was administered to 6 patients (bladder cancer and transitional cell carcinoma), intra-arterially in two cases. One patient showed a complete response and survived for 7 months, three partial response (PR) surviving for 13, 8 and 37 (arterial-infused case) months, one showed minor response (MR) surviving for 4 months, and one had no change (NC) surviving for 5 months. VPM-CisCF (II) was administered to 11 patients (1 ureteral cancer, 1 renal pelvic cancer, 9 bladder cancer, and 10 transitional cell carcinoma except a case of mixed type of transitional cell carcinoma and squamous cell carcinoma). Four of the patients who had PR survived for 9, 8, 8 and 7 (alive) months, two who had MR survived for 8 and 4 months, three who had NC survived for 6, 4 and 4 months, and who two had progressive disease survived for 8 and 6 months. The major toxicities were myelosuppression and gastrointestinal symptoms, especially nausea and vomiting, but the treatment was well-tolerated.

[Transitional cell carcinoma in the ureter showing inverted proliferation: a case report].

A case of transitional cell carcinoma in the ureter showing inverted proliferation is reported. A tumor in the middle third of the right ureter was found in a 67-year-old male complaining of gross hematuria. Since positive findings of malignancy were obtained in a washing examination of urine cytology, right nephroureterectomy was performed. The gross specimen consisted of a polypoid and pedunculated 22 x 8 mm tumor which showed a smooth surface as in normal ureteral mucosa. Histopathologically, the tumor was lined with normal transitional epithelium but filled with transitional cell carcinoma, grade 1. Diagnosis and treatment of ureteral tumors showing inverted proliferation are discussed.