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Precise quantification of copy‐number alterations (CNAs) in a tumor genome is difficult. We have applied a comprehensive copy‐number analysis method, digital multiplex ligation‐dependent probe amplification (digitalMLPA), for targeted gene copy‐number analysis in clear cell renal cell carcinoma (ccRCC). Copy‐number status of all chromosomal arms and 11 genes was determined in 60 ccRCC samples. Chromosome 3p loss and 5q gain, known as early changes in ccRCC development, as well as losses at 9p and 14q were detected in 56/60 (93.3%), 31/60 (51.7%), 11/60 (18.3%), and 33/60 (55%), respectively. Through gene expression analysis, a significant positive correlation was detected in terms of 14q loss determined using digitalMLPA and downregulation of mRNA expression ratios with HIF1A and L2HGDH (P =.0253 and.0117, respectively). Patients with early metastasis (<1 y) (n = 18) showed CNAs in 6 arms (in median), whereas metastasis‐free patients (n = 34) showed those in significantly less arms (3 arms in median) (P =.0289). In particular, biallelic deletion of CDKN2A/2B was associated with multiple CNAs (≥7 arms) in 3 tumors. Together with sequence‐level mutations in genes VHL, PBRM1, SETD2, and BAP1, we performed multiple correspondence analysis, which identified the association of 9p loss and 4q loss with early metastasis (both P <.05). This analysis indicated the association of 4p loss and 1p loss with poor survival (both, P <.05). These findings suggest that CNAs have essential roles in aggressiveness of ccRCC. We showed that our approach of measuring CNA through digitalMLPA will facilitate the selection of patients who may develop metastasis. [ABSTRACT FROM AUTHOR]

One factor explaining the declining birth rate in Japan is the social advancement of women. Women are delaying marriage and childbirth, with many then facing so-called 'social infertility'. Advanced infertility treatment options, such as in vitro fertilization, are available, but the costs are high. Further, the success rates for 'older' women are only around 10%. We report the preliminary results of an oocyte cryopreservation programme promoted and subsidized by our city government. Citywide seminars were conducted to generate awareness of issues surrounding fertility. Among the total 81 attendees were women considering oocyte retrieval and the current practice of oocyte retrieval and cryopreservation and its associated risks were explained. Fifty-seven attendees, women under 34 years of age, were considered potential candidates for the procedure. These women wished to delay pregnancy for specific reasons, such as occupational demands. Twenty-six of these women expressed a definite desire for oocyte cryopreservation, and 19 have thus far completed the oocyte retrieval and cryopreservation procedure. Frozen MII oocytes have ranged in number from 3 to 22 per patient (mean ± SD, 8.3 ± 5.2). Outcomes thus far indicate that women whose fertility is at risk can be assisted by this fertility preservation method and that it will help address the problem of the declining birth rate in Japan. [ABSTRACT FROM AUTHOR]

Background/Aims: α-Klotho is mainly expressed in the kidneys, and its soluble form can prevent vascular calcifications. Inhibition of the mammalian target of rapamycin (mTOR) upregulates Klotho. We assessed serial changes in the levels of soluble Klotho (sKlotho) in recipients before and after renal transplantation and investigated the effects of an mTOR inhibitor. Methods: Serum sKlotho levels were measured in 36 recipients before and 1 year after transplantation and compared between those taking everolimus and those not taking everolimus. Results: sKlotho levels were higher after transplantation than before transplantation (369.3 vs. 211.8 pg/mL). After transplantation, sKlotho levels were significantly higher in recipients taking everolimus than in those not taking everolimus (536.7 vs. 332.4 pg/mL). Conclusion: Our results suggest that mTOR inhibition may augment the increase in sKlotho levels in transplant recipients. Further studies are needed to examine whether mTOR inhibitors suppress the development of vascular complications via upregulation of Klotho expression in renal transplant recipients. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate renal cell carcinoma (RCC) findings in acquired cystic disease of the kidney (ACDK) shown by 11C-choline and FDG PET/CT, and contrast-enhanced CT.Materials and Methods: Six ACDK patients with 7 RCCs underwent 11C-choline and FDG PET/CT, and contrast-enhanced CT before nephrectomy. Findings obtained with 3 imagings were evaluated and sensitivity detecting RCC was compared using 3-point grading scale (negative, equivocal, positive). The equivocal scale used for SUVmax ranged from 2.0 to 3.0 for PET/CT and a peak enhancement value ranging from 20 to 30 HU was used for CT.Result: The histopathologic subtypes of 7 RCCs were clear-cell (n = 4) and ACD-associated RCC (n = 3). The negative/equivocal/positive grading results were 0/0/7 for 11C-choline-PET/CT, 0/3/4 for FDG-PET/CT, and 2/2/3 for CT. Three equivocal cases by FDG-PET/CT were 2 clear-cell RCCs and 1 ACD-associated RCC. CT of 3 ACD-associated RCCs showed negativity for 2 and equivocality for 1. Sensitivity defining equivocal interpretation as negative for 11C-choline-PET/CT, FDG-PET/CT, and CT was 100% (7/7), 57.1% (4/7), and 42.9% (3/7).Conclusion: 11C-choline-PET/CT was more sensitive to detect RCC in ACDK as compared to FDG-PET/CT and contrast-enhanced CT in our series. FDG-PET/CT may be limited for detecting clear-cell RCC, while CT may have difficulty with detection of ACD-associated RCC. [ABSTRACT FROM AUTHOR]

Purpose: To compare findings obtained with 11C-choline and FDG PET/CT scanning for renal cell carcinoma staging and restaging.Materials and Methods: Twenty-eight renal cell carcinoma patients whose histological subtype was clear cell type in 26 and papillary type in 2, while Fuhrman nuclear grade was G1,2 in 16 and G3,4 in 12, underwent both 11C-choline and FDG PET/CT examinations before (n = 10) and/or after (n = 18) treatment, then those scanning modalities were compared in regard to patient- and lesion-based diagnostic performance using 5 grading scores. Final diagnosis in each case was obtained based on histopathology, conventional radiological imaging, and clinical follow-up findings. The differences between 11C-choline and FDG PET/CT findings were evaluated using receiver-operating-characteristic (ROC) analysis and a McNemar test.Results: Patient-based sensitivity, specificity, positive predictive, negative predictive, accuracy, and area under the ROC curve (AUC) values for 11C-choline PET/CT for staging and restaging were 88.0% (22/25), 66.7% (2/3), 95.7% (22/23), 40.0% (2/5), 85.7% (24/28), and 0.887, respectively, while those for FDG-PET/CT were 56.0% (14/25), 66.7% (2/3), 93.3% (14/15), 15.4% (2/13), 57.1% (16/28), and 0.647, respectively. Sensitivity, accuracy, and AUC were significantly different (p = 0.013, p = 0.013, p = 0.012, respectively). Among the 120 lesions, those with kidney, lung, lymph node, bone, pancreas, venous tumor thrombosis, adrenal gland, liver, or skin localization numbered 15, 64, 16, 13, 4, 3, 2, 2, and 1, respectively. For all 120 lesions, 75 (62.5%) and 47 (39.2%) were detected by 11C-choline and FDG PET/CT, respectively (p < 0.0001).Conclusion: For staging and restaging of renal cell carcinoma patients, 11C-choline-PET/CT is significantly more useful than FDG-PET/CT. [ABSTRACT FROM AUTHOR]

Purpose We previously attempted to develop quantitative enzyme-linked immunosorbent assay (ELISA) systems for the PDA039/044/071 peptides, potential serum disease biomarkers (DBMs) of pregnancy-induced hypertension (PIH), primarily identified by a peptidomic approach (BLOTCHIP®-mass spectrometry (MS)). However, our methodology did not extend to PDA071 (cysteinyl α2-HS-glycoprotein341-367), due to difficulty to produce a specific antibody against the peptide. The aim of the present study was to establish an alternative PDA071 quantitation system using liquid chromatography-multiple reaction monitoring (LC-MRM)/MS, to explore the potential utility of PDA071 as a DBM for PIH. Methods We tested heat/acid denaturation methods in efforts to purify serum PDA071 and developed an LC-MRM/MS method allowing for specific quantitation thereof. We measured serum PDA071 concentrations, and these results were validated including by three-dimensional (3D) plotting against PDA039 (kininogen-1439-456)/044 (kininogen-1438-456) concentrations, followed by discriminant analysis. Results PDA071 was successfully extracted from serum using a heat denaturation method. Optimum conditions for quantitation via LC-MRM/MS were developed; the assayed serum PDA071 correlated well with the BLOTCHIP® assay values. Although the PDA071 alone did not significantly differ between patients and controls, 3D plotting of PDA039/044/071 peptide concentrations and construction of a Jackknife classification matrix were satisfactory in terms of PIH diagnostic precision. Conclusions Combination analysis using both PDA071 and PDA039/044 concentrations allowed PIH diagnostic accuracy to be attained, and our method will be valuable in future pathophysiological studies of hypertensive disorders of pregnancy. [ABSTRACT FROM AUTHOR]

Choline is a new positron emission tomography (PET) tracer useful for detection of prostate cancer and metastatic lesions. We report a 70-year-old man with prostate cancer and multiple abdominal, pelvic, and inguinal node metastases. PET scans demonstrated accumulation of 11C-choline in the primary tumor and lymph node metastases but no accumulation of 18FFDG. Choline PET/computed tomography may be useful for diagnosis of advanced prostate cancer with suspected metastatic lesions and treatment planning. [ABSTRACT FROM AUTHOR]

Background: We previously reported peptide candidates of disease biomarkers for pregnancy-induced hypertension syndrome using a novel peptidomic analytical method, BLOTCHIP®-MS. The aim of this study was to establish a sandwich enzyme-linked immunosorbent assay system for quantitation of such peptides and to validate their usefulness as disease biomarkers of pregnancy-induced hypertension syndrome including gestational hypertension/pre-eclampsia.Methods: We focused on three peptide fragments, kininogen-1439-456 (PDA039), kininogen-1438-456 (PDA044) and cysteinyl α2-HS-glycoprotein341-367 (PDA071). Using polyclonal antibodies specific for each peptide, suitable conditions for the sandwich enzyme-linked immunosorbent assay system were investigated. The quantitative enzyme-linked immunosorbent assay values were confirmed by quantitative matrix assisted laser desorption/ionization time-of-flight MS analyses. Using the established enzyme-linked immunosorbent assay systems, serum samples from gestational hypertension/pre-eclampsia patients and paired serum samples from healthy pregnant females were analysed.Results: The optimum sandwich enzyme-linked immunosorbent assay conditions for PDA039/044 quantitation were developed. Quantitation of PDA071 by enzyme-linked immunosorbent assay failed, presumably due to issues with polyclonal antibody specificity for the native peptide. Bland-Altman plots showed a satisfactory correlation between the serum PDA039/044 concentration by enzyme-linked immunosorbent assay and that by quantitative MS analysis. Although the PDA044 concentration showed no significant change during pregnancy, including gestational hypertension/pre-eclampsia patients, the serum PDA039 concentration was significantly increased (P < 0.0001) in the patients.Conclusions: The simple quantitation technology for PDA039 by enzyme-linked immunosorbent assay was established for the first time. PDA039 confirmed its clinical utility as a disease biomarker for gestational hypertension/pre-eclampsia by the enzyme-linked immunosorbent assay system using clinical samples. The information provided from the present study would be a new valuable addition in the field of gestational hypertension/pre-eclampsia research. [ABSTRACT FROM AUTHOR]

TEX101, a member of the Ly-6/urokinase-type plasminogen activator receptor (LU)-family we previously identified, is a germ cell-marker glycoprotein. To date, it is reported that some members of the protein-family are overexpressed in a variety of cancer tissues. We previously reported Ly6k, a member of the LU-family, as an association molecule with TEX101 in murine male germ cells. LY6K (a human homologue of Ly6k) is overexpressed in head and neck squamous cell carcinomas (HNSCC). These facts led us to speculate that TEX101 may also exist in HNSCC, like LY6K. Using an anti-human TEX101 polyclonal antibody (pAb) established, we examined the expression of TEX101 protein in cancer tissues by immunohistochemical analysis. TEX101 was detected in the cancer cells of some tissue specimens from patients with HNSCC, whereas the normal squamous epithelium was immunonegative. The TEX101 protein was detected in cancer cells from 54 out of 64 (80.6%) patients with HNSCC. The rate of lymph nodes metastasis tends to be low in TEX101-positive patients, compared to patients with weakly positive and negative expression of TEX101. The present results imply that TEX101 is a novel cancer-related protein and may be useful as a marker for prognosis/diagnosis of HNSCC. [ABSTRACT FROM AUTHOR]

We report our initial experience with salvage therapy for low responders to PDE-5 inhibitors by adding vitamin E. Of 89 patients with ED who visited our clinic between January 2004 to August 2006, 9 were unable to obtain a full response to a PDE-5 inhibitor and included in the present study. After providing informed consent, each was given 300 mg per day of α-tocophenol at least 1 month and completed IIEF-5 questionnaires to assess its efficacy while also taking a PDE-5 inhibitor. With α-tocophenol administration, the average IIEF-5 score increased from 13.8±3.2 to 17.1±3.6. Four of seven patients who completed the questionnaire each time showed improved IIEF-5 scores, with a maximum elevation of 9 points. Further, eight of the nine patients experienced favourable subjective changes, the majority being increased penile rigidity. The present clinical trial results are, to our knowledge, the first known to show the effects of vitamin E for enhancing the efficacy of a PDE-5 inhibitor. [ABSTRACT FROM AUTHOR]

Objective: To present the usefulness of fetal magnetic resonance (MR) imaging for accurate diagnosis of Pfeiffer syndrome type II. Case and Methods: A 19-year-old woman was referred to us at 29 weeks of gestation for prenatal management of hydrocephalus. Ultrasonography of the fetus showed cloverleaf skull with dilated lateral ventricles, exophthalmos, macroglossia, and a single ventricle of the heart in addition to polyhydramnios. MR imaging was performed at 30 weeks of gestation and revealed cloverleaf skull, dilated lateral ventricles, and broad thumb. Fetal karyotyping indicated 46,XY, but DNA sequence analysis showed a single sequence variation (Nt 1198A>G) in the fibroblast growth factor receptor (FGFR) 2 gene (exon 10). On the basis of these findings, the baby was diagnosed in utero with Pfeiffer syndrome type II. Following counseling, the pregnancy was terminated because polyhydramnios made the patient’s symptoms more severe. The patient delivered her baby vaginally at 34 weeks of gestation. The baby’s birth weight was 2,298 g; the baby was declared dead at 25 min after birth. Conclusion: The detailed findings obtained by a combination of ultrasound that included three-dimensional and MR imaging and confirmation sought via molecular testing led to an accurate diagnosis of Pfeiffer syndrome type II in utero. Copyright © 2006 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

A polyp of about 1.0 cm diameter was incidentally found at the center of theposterior wall of the urinary bladder in a 73-year-old man on cystoscopicexamination. A polyp was resected through a transurethral route withoutrecurrence for 22 months. A polyp consisted of a tumor covered with mucosaof the bladder. Tumor cells have round or oval nuclei with fine chromatinand one or two nucleoli per nucleus, and finely granular eosinophiliccytoplasm, being arranged in a trabecular or tubular pattern. Furthermore,they showed positive staining for chromogranin-A and with Grimelius stain,indicating that the tumor is a carcinoid tumor. Since there was no evidenceof carcinoid tumors in organs other than the urinary bladder, the presentcase is a primary carcinoid tumor (well differentiated endocrine tumor) ofthe urinary bladder which is extremely rare. [ABSTRACT FROM AUTHOR]