[Carcinoma of the small intestine diagnosed by double balloon endoscopy].

There are no specific symptoms of patients with carcinoma of the small intestine. Therefore, it is difficult to diagnose in the early stage by imaging modalities such as radiological enteroclysis, computed tomography, and classical endoscopy. However, double balloon endoscopy makes it possible to diagnose the carcinoma of the entire small bowel by taking tissue samples for pathological assessment. The characteristic of endoscopic findings is irregular ulcerated tumor with malignant stricture. It is still difficult to find carcinoma of small intestine in patients without symptoms and most cases are advanced when diagnosis is achieved. We should try to diagnose in early stage by combining images modalities, capsule endoscopy and double balloon endoscopy safely and efficiently, resulting in improving the patients' prognosis.

[A case of pulmonary hyalinizing granuloma with high-grade uptake on FDG-PET mimicking metastatic lung cancer].

A 28-year-old man was referred to Hakodate Municipal Hospital for examination of multiple pulmonary nodules detected on a medical check-up. His chest CT demonstrated well-defined multiple nodules with random distribution. 18-fluorodeoxyglucose positron emission tomography (FDG-PET) showed abnormal uptake in the pulmonary nodules and the hilar, mediastinal lymph node. No other accumulation was observed outside the thorax. Transbronchial lung biopsy did not yield a diagnosis. Based on the high accumulation on FDG-PET, we suspected a malignant tumor and performed right S4 wedge resection under video assisted thoracoscopy. Considering the histologocal and immunohistological findings, we diagnosed pulmonary hyalinizing granuloma. No treatment was given and subsequently stable disease was obtained on chest radiography. The follow-up FDG-PET showed standardized uptake value reduction. Pulmonary hyalinizing granuloma is infrequent and benign, but has been reported to possibly progress to lymphoproliferative disease. Consequently, FDG-PET is valuable to evaluate the activity of the disease itself and the possibility of transition.

Initial Diagnosis of Mediastinal Lymph Node Metastases From Prostate Cancer by Endobronchial Ultrasound-guided Transbronchial Needle Aspiration.

A 61-year-old patient with multiple enlarged mediastinal and hilar lymph nodes (♯3a, ♯4R, ♯7, and ♯11) and no abnormal shadows in the lung field by chest computed tomography was referred to our department for further evaluation. Endobronchial ultrasound-guided transbronchial needle aspiration was performed; cytology revealed adenocarcinoma, whereas histology contained adenocarcinoma of prostate origin. Immunohistochemistry was strongly positive for prostate-specific antigen and prostate-specific acid phosphate for confirmation of metastases from the prostate cancer and negative for thyroid transcription factor-1. Hence, the patient was diagnosed as having lymph node metastasis from a prostate cancer. After the initial diagnosis, needle biopsy of the prostate was performed, and prostate cancer was confirmed. The patient received hormonal therapy and has remained in stable condition. Endobronchial ultrasound-guided transbronchial needle aspiration provides tissue for histologic examination, including immunohistochemistry, from mediastinal and hilar lymph nodes involved with metastasis from a distal primary site.

Localization and roles in fertilization of sperm proteasomes in the ascidian Halocynthia roretzi.

We previously reported that sperm proteasome is responsible for degradation of the ubiquitinated vitelline-coat during fertilization in the ascidian Halocynthia roretzi. Here, we report the roles in fertilization and localization in the sperm cell surface of H. roretzi sperm proteasome. An anti-proteasome antibody, as well as the proteasome inhibitors MG115 and MG132, inhibited the fertilization, indicating that the sperm proteasome functions extracellularly in ascidian fertilization. In order to further assess this issue, the sperm surface proteasome activity was labeled with a cell-impermeable labeling reagent, NHS-LC-biotin, extracted with 0.1% CHAPS, and was subjected to a pull-down assay with avidin-agarose beads. It was found that a substantial amount of sperm proteasome is exposed to the cell surface. Partition analysis with Triton X-114 also revealed that a considerable amount of the sperm proteasome activity is partitioned into a lipid layer. Localization of the proteasome activity was investigated by fluorescence microscopy with succinyl-Leu-Leu-Val-Tyr-4-methylcoumaryl-7-amide as a substrate. The sperm proteasome activity was specifically detected in the sperm head region, and it was markedly activated upon sperm activation. The membrane-associated proteasome was purified from the membrane fraction of H. roretzi sperm by affinity chromatography using an anti-20S proteasome antibody-immobilized Sepharose column. SDS-PAGE of the purified preparation showed a similar pattern of subunit composition to that of the 26S proteasome of mammalian origin. Taken together, these results indicate that H. roretzi sperm has the membrane-associated proteasome on its head, which is activated upon sperm activation, and that sperm proteasome plays an essential role in H. roretzi fertilization.

Extracellular ubiquitination and proteasome-mediated degradation of the ascidian sperm receptor.

The ubiquitin-proteasome system is essential for intracellular protein degradation, but an extracellular role of this system has not been known until now. We have previously reported that the proteasome is secreted into the surrounding seawater from sperm of the ascidian (Urochordata) Halocynthia roretzi on sperm activation, and that the sperm proteasome plays a key role in fertilization. Here, we show that a 70-kDa component (HrVC70) of the vitelline coat is the physiological substrate for the ubiquitin-proteasome system during fertilization of H. roretzi. A cDNA clone encoding the HrVC70 precursor (HrVC120) was isolated, and a homology search revealed that HrVC120 contains 13 epidermal growth factor-like repeats and a mammalian zona pellucida glycoprotein-homologous domain. HrVC70 functions as a sperm receptor. We demonstrate that HrVC70 is ubiquitinated both in vitro and in vivo. The immunocytochemical localization of multiubiquitin chains in the vitelline coat and the inhibitory effect of monoclonal antibodies against the multiubiquitin chains on fertilization strongly support the role of the ubiquitin-proteasome system in ascidian fertilization. Taken together, these results indicate that the ubiquitin-proteasome system is responsible for extracellular degradation of the sperm receptor HrVC70 and, consequently, for sperm penetration of the vitelline coat during fertilization.