A 10-year experience of totally extraperitoneal endoscopic repair for adult inguinal hernia.

PURPOSE: Laparoscopic surgery is fast becoming the treatment of choice for inguinal hernia. By reviewing our 10-year experience of performing totally extraperitoneal repair (TEP), we sought to establish its clinical significance in the treatment of adult inguinal hernia. METHODS: We reviewed retrospectively the clinical records of patients who underwent TEP for adult inguinal hernia between January 2003 and December 2012. RESULTS: None of the 303 patients with adult primary or recurrent inguinal hernia in our study needed TEP converted to other procedures or suffered serious complications during the procedure. A significant difference was noted in the operation time between direct (n = 32) vs indirect (n = 128) hernias in the primary unilateral inguinal hernia group (91 ± 27 vs 80 ± 32 min, p = 0.033) and between direct/direct (n = 31) vs indirect/indirect (n = 24) hernias (136 ± 58 vs 89 ± 24 min, p = 0.01) in the primary bilateral inguinal hernia group. The only postoperative complications recorded were four cases of hernia recurrence (1.3 %) and one case of chronic pain (0.3 %). CONCLUSIONS: The results obtained for TEP over 10 years support this as a promising procedure for the treatment of adult inguinal hernia.

Visualization-based medical expenditure analysis support system.

Japanese municipalities have recently been required to decrease their medical expenditure, which has been expanding as a result of an increasing number of patients with chronic diseases. We attempted to visualize insurance claim data to support medical expenditure analysis for insurers or local government (e.g. cities, towns and villages). We introduce two perspectives for the visualization of medical expenditure data: the general perspective approach to understanding overall medical expenditure and the specific perspective approach focused on particular issues such as lifestyle-related diseases. We have created the visual primitives, which enables interactive visualization for very large datasets, from raw insurance claim data. This system uses hypertext markup language and Data-driven Documents and provides analysis support for a comprehensive understanding of overall medical expenditure and comparisons between municipalities over time.

Auto-regulation of the Sohlh1 gene by the SOHLH2/SOHLH1/SP1 complex: implications for early spermatogenesis and oogenesis.

Tissue-specific basic helix-loop-helix (bHLH) transcription factor proteins often play essential roles in cellular differentiation. The bHLH proteins SOHLH2 and SOHLH1 are expressed specifically in spermatogonia and oocytes and are required for early spermatogonial and oocyte differentiation. We previously reported that knocking out Sohlh2 causes defects in spermatogenesis and oogenesis similar to those in Sohlh1-null mice, and that Sohlh1 is downregulated in the gonads of Sohlh2-null mice. We also demonstrated that SOHLH2 and SOHLH1 can form a heterodimer. These observations led us to hypothesize that the SOHLH2/SOHLH1 heterodimer regulates the Sohlh1 promoter. Here, we show that SOHLH2 and SOHLH1 synergistically upregulate the Sohlh1 gene through E-boxes upstream of the Sohlh1 promoter. Interestingly, we identified an SP1-binding sequence, called a GC-box, adjacent to these E-boxes, and found that SOHLH1 could bind to SP1. Furthermore, chromatin-immunoprecipitation analysis using testes from mice on postnatal day 8 showed that SOHLH1 and SP1 bind to the Sohlh1 promoter region in vivo. Our findings suggest that an SOHLH2/SOHLH1/SP1 ternary complex autonomously and cooperatively regulates Sohlh1 gene transcription through juxtaposed E- and GC-boxes during early spermatogenesis and oogenesis.

[A case of multiple para-aortic lymph node metastases from squamous cell carcinoma of an unknown primary responding completely to chemotherapy].

We report a case of disease -free survival with combination chemotherapy against squamous cell carcinoma(SCC)of an unknown primary. A 54-year-old male had an intraabdominal malignant lymph node tumor beside the common hepatic artery which was revealed by image studies including CT, MRI and PET-CT. After extirpation of the tumor, the resected specimens were diagnosed as metastatic SCC in the lymph nodes by pathology and immunohistochemistry. Cancers of an unknown primary are divided into two sub-groups, favorable and unfavorable, based on their clinical output. During hesitation to cure because of the unfavorable sub-group, the authors recognized multiple Virchow's and para-aortic lymph node metastases in this case. However, chemotherapy with CDDP/5-FU, followed by S-1, and then DOC were effective, resulting in a CR. The patient has been well without any sign of recurrence over 3 years after the first chemotherapy and about 2 years after the last chemotherapy. If a primary site is not found immediately after careful detection cancer of an unknown primary should be cured.

[A case of synchronous hepatic and multiple pulmonary metastases from rectal cancer responding completely to UFT therapy after resection of primary and hepatic lesions].

We report a case of disease-free survival with uracil-tegafur(UFT)therapy after resection of primary and hepatic lesions from rectal cancer. A 64-year-old female had synchronous hepatic and multiple pulmonary metastases from rectal cancer. Image studies including colonoscopy, CT, MRI and PET-CT showed 2 metastases of lung(rt. middle lobe and lt. upper lobe) and a metastasis of liver(S6)in addition to rectal cancer(Rb, pSM, pN1, ly2, v1). Abdominoperineal resection+D3 of rectal cancer was performed, followed by chemotherapy with UFT for 28 days, and then partial resection of liver. Resected specimens of the liver demonstrated a histological Grade 2 with many CD3-positive lymphocytes. After surgeries, chemotherapy with UFT was continued, resulting in a CR for pulmonary metastases. The patient has been well without any sign of recurrence 5 years after first surgery. This case indicated that UFT was effective for hepatic and pulmonary metastases from rectal cancer, partially due to T cells(CD3+)infiltrating the metastases.

Maternal-effect gene Ces5/Ooep/Moep19/Floped is essential for oocyte cytoplasmic lattice formation and embryonic development at the maternal-zygotic stage transition.

In a search for genes specifically expressed in mouse embryonic stem cells, we identified one we called Ces5. We found that it corresponded to the Ooep gene, which was recently reported to be expressed specifically in oocytes. Mouse Ces5/Ooep, also called Moep19 or Floped, encoded a 164-amino acid protein, which was detected in the cytoplasm of developing and mature oocytes and in embryos throughout the preimplantation period. To examine its function, we carried out targeted disruption of this gene. The Ces5/Ooep-null mice were grossly normal, but the females were infertile. Although the ovaries and ovulation appeared normal, the embryos from Ces5/Ooep-null females mated with wild-type males showed developmental arrest at the two- or four-cell stage. In addition, their first cleavage was considerably delayed and often asymmetrical. Thus, Ces5/Ooep is a maternal-effect gene. By electron microscopy, we found that the eggs from Ces5/Ooep-null females lacked oocyte cytoplasmic lattices (CPLs), which have long been predicted to function as a storage form for components that are maternally contributed to the early embryo. Further analysis showed that CES5/OOEP was directly associated with the CPLs. These results indicate that CES5/OOEP is an essential component of the CPLs and is required for embryonic development at the maternal-zygotic stage transition.

Gtsf1/Cue110, a gene encoding a protein with two copies of a CHHC Zn-finger motif, is involved in spermatogenesis and retrotransposon suppression in murine testes.

We recently reported that the Gtsf1/Cue110 gene, a member of the evolutionarily conserved UPF0224 family, is expressed predominantly in male germ cells, and that the GTSF1/CUE110 protein is localized to the cytoplasm of these cells in the adult testis. Here, to analyze the roles of the Gtsf1/Cue110 gene in spermatogenesis, we produced Gtsf1/Cue110-null mice by gene targeting. The Gtsf1/Cue110-null mice grew normally and appeared healthy; however, the males were sterile due to massive apoptotic death of their germ cells after postnatal day 14. In contrast, the null females were fertile. Detailed analyses revealed that the Gtsf1/Cue110-null male meiocytes ceased meiotic progression before the zygotene stage. Thus, the Gtsf1/Cue110 gene is essential for spermatogenesis beyond the early meiotic phase. Furthermore, the loss of the Gtsf1/Cue110 gene caused increased transcription of the long interspersed nucleotide element (Line-1) and the intracisternal A-particle (IAP) retrotransposons, accompanied by demethylation of their promoter regions. These observations indicate that Gtsf1/Cue110 is required for spermatogenesis and involved in retrotransposon suppression in male germ cells.

Sohlh2 affects differentiation of KIT positive oocytes and spermatogonia.

The differentiation programs of spermatogenesis and oogenesis are largely independent. In the early stages, however, the mechanisms partly overlap. Here we demonstrated that a germ-cell-specific basic helix-loop-helix (bHLH) transcription factor gene, Sohlh2, is required for early spermatogenesis and oogenesis. SOHLH2 was expressed in mouse spermatogonia from the undifferentiated stage through differentiation and in primordial-to-primary oocytes. Sohlh2-null mice, produced by gene targeting, showed both male and female sterility, owing to the disrupted differentiation of mature (KIT(+)) spermatogonia and oocytes. The Sohlh2-null mice also showed the downregulation of genes involved in spermatogenesis and oogenesis, including the Sohlh1 gene, which is essential for these processes. Furthermore, we showed that SOHLH2 and SOHLH1 could form heterodimers. These observations suggested that SOHLH2 might coordinate with SOHLH1 to control spermatogonial and oocyte genes, including Sohlh1, to promote the differentiation of KIT(+) germ cells in vivo. This study lays the foundation for further dissection of the bHLH network that regulates early spermatogenesis and oogenesis.

Transgenic expression of antioxidant protein thioredoxin in pancreatic beta cells prevents progression of type 2 diabetes mellitus.

The authors previously established a transgenic mouse line in the type 1 diabetes model, NOD mouse, in which thioredoxin (TRX), a redox protein, is overexpressed in pancreatic beta cells, and found that TRX overexpression slows the progression of type 1 diabetes. Recent reports on type 2 diabetes suggest that oxidative stress also degrades the function of beta cells. To elucidate whether TRX overexpression can prevent progressive beta cell failure from oxidative stress in type 2 diabetes, the authors transferred the TRX transgene from the NOD mouse onto a mouse model of type 2 diabetes, the db/db mouse. The progression of hyperglycemia and the reduction of body weight gain and insulin content of the db/db mouse were significantly suppressed by the TRX expression. Furthermore, TRX suppressed the reduction of Pdx-1 and MafA expression in the beta cells, which may be one of the cellular mechanisms for protecting beta cells from losing their insulin-secreting capacity. These results showed that TRX can protect beta cells from destruction not only in type 1 but also in type 2 diabetes, and that they provide evidence that oxidative stress plays a crucial role in the deterioration of beta cell function during the progression of type 2 diabetes.

Two intelligent order viewers for chronic condition patients on clinical information system.

The computerization of patient data is proceeding and the amount of patient records has greatly increased. However, physicians have limited time to review and process patient records. In order to use these records effectively, medical institutions need to access the information in a variety of forms. This paper comparatively describes two intelligent viewers that are SAKURA-Viewer and FUJI-Viewer. These viewers reorganize order-related data. SAKURA-Viewer is based on a concept hierarchy method and focuses the view of consolidated information. This viewer represents order history from two viewpoints simultaneously to eliminate semantic redundancies. FUJI-Viewer is based on two-dimensional mapping method and focuses the flow of periodic information. This viewer represents differences between the plan history and the order history to manage a long-term test order history and test plan history concurrently. These viewers also support data entry methods that input order-related data efficiently and accurately. This interface reduces the workload of the medical stuff. These intelligent viewers are incorporated into a clinical information system.

Gene expression pattern of Cue110: a member of the uncharacterized UPF0224 gene family preferentially expressed in germ cells.

The large number of expressed sequence tags (ESTs) now available in databases has enabled the analysis of gene expression profiles in silico. We searched public databases for uncharacterized transcripts specifically expressed in germ cells, in an attempt to identify genes involved in gametogenesis. We found a transcript that is expressed in unfertilized eggs, ovaries, and testes of the mouse. It has an open reading frame (ORF) encoding a 167-amino acid protein belonging to the UPF0224 (unknown protein family 0224) family. We called the novel gene Cue110. We examined the Pfam database for other members of the UPF0224 family, and found a conserved N-terminal portion among members of various species. To study the cellular localization of the Cue110 transcript and protein, we performed in situ hybridization and immunohistochemical analysis of the adult mouse ovary and testis. In the testis, specific hybridization signals were observed weakly in preleptotene spermatocytes but maximally in late round spermatids. Immunostaining showed that Cue110 protein was present predominantly in the cytoplasm of pachytene spermatocytes and round spermatids. In the ovary, weak hybridization signals were observed in primary oocytes in the primordial, primary, and secondary follicles, but Cue110 protein was not detected in oocytes by immunostaining. We next examined the developmental expression pattern of the Cue110 gene using RT-PCR and western blotting, and found its increasing expression coincided with the appearance of spermatocytes. Thus, the Cue110 gene is expressed predominantly in male germ cells at stages from the pachytene spermatocytes to round spermatids.

Tissue-specific deletion of c-Jun in the pancreas has limited effects on pancreas formation.

It is well known that activating protein-1 (AP-1) is involved in a variety of cellular functions such as proliferation, differentiation, apoptosis, and oncogenesis. AP-1 is a dimer complex consisting of different subunits, and c-Jun is known to be one of its major components. In addition, it has been shown that mice lacking c-Jun are embryonic lethal and that c-Jun is essential for liver and heart development. However, the role of c-Jun in the pancreas is not well known. The aim of this study was to examine the possible role of c-Jun in the pancreas. First, c-Jun was strongly expressed in pancreatic duct-like structures at an embryonic stage, while a lower level of expression was observed in some part of the adult pancreas, implying that c-Jun might play a role during pancreas development. Second, to address this point, we generated pancreas-specific c-Jun knock-out mice (Ptf1a-Cre; c-Jun(flox/flox) mice) by crossing Ptf1a-Cre knock-in mice with c-Jun floxed mice. Ptf1a is a pancreatic transcription factor and its expression is confined to pancreatic stem/progenitor cells, which give rise to all three types of pancreatic tissue: endocrine, exocrine, and duct. Contrary to our expectation, however, there was no morphological difference in the pancreas between Ptf1a-Cre; c-Jun(flox/flox) and control mice. In addition, there was no difference in body weight, pancreas weight, and the expression of various pancreas-related factors (insulin, glucagon, cytokeratin, and amylase) between the two groups. Furthermore, there was no difference in glucose tolerance between Ptf1a-Cre; c-Jun(flox/flox) and control mice. Taken together, although we cannot exclude the possibility that c-Jun ablation is compensated by some unknown factors, c-Jun appears to be dispensable for pancreas development at least after ptf1a gene promoter is activated.

SAKURA-viewer: intelligent order history viewer based on two-viewpoint architecture.

We propose a new intelligent order history viewer applied to consolidating and visualizing data. SAKURA-viewer is a highly effective tool, as: 1) it visualizes both the semantic viewpoint and the temporal viewpoint of patient records simultaneously; 2) it promotes awareness of contextual information among the daily data; and 3) it implements patient-centric data entry methods. This viewer contributes to decrease the user's workload in an order entry system. This viewer is now incorporated into an order entry system being run on an experimental basis. We describe the evaluation of this system using results of a user satisfaction survey, analysis of information consolidation within the database, and analysis of the frequency of use of data entry methods.

FUJI-Scheduler: outpatient-test-order-management function for order entry system.

The computerization of medical institutions as part of the social infrastructure is one of the priority elements referred to in the government's e-Japan Strategy. The computerization of patient data is currently making progress, and these are being accumulated by medical institutions as massive volumes of patient data. In order to use these records effectively, therefore, medical institutions require the capability to represent patient records in a variety of different forms that aid in understanding the information, the capability to share patient records among multiple medical institutions, the capability to support the systematic and effective provision of medical care, and other such functionality. In this paper, the clinical planning for the outpatient medical care of chronic disease patients and the data representation for EPR system are investigated. This paper also describes the order entry system that incorporates FUJI-Scheduler that supports formulating test order schedule and the function that efficiently represents the past test order data and the future test order data. This system is able to create annual test schedules for each patient and automatically create test orders using the plan. It also provides a new user interface that reduces the workload of the people who create the plans. This system is presently being operated on an experimental basis.