Department of Advanced Transplant and Regenerative Medicine has been established in Hirosaki University Graduate School of Medicine by a donation of Oyokyo kidney research institute on October 1, 2010. Transplant law took effect on October 16th, 1997, then 2 organ donations from brain dead cadaver happened in Aomori prefecture. The revised transplant law was enforced on July 17, 2010 and numbers of brain dead donor are currently increasing in Japan. However, total number of donations including non-heart beating donor remain almost the same numbers. Herein we introduce a history of organ transplantation especially of the kidney and the liver in Aomori prefecture and discuss current circumstance and problems on donation and transplantation in Aomori and Japan. Finally, we introduce our current strategy for expansion and enlightenment of organ donation and transplantation in Aomori.

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Objective: Collagen peptides have recently been shown to have several biological activities, and have been used as preservatives and immunotherapeutic agents. The purpose of this study was to investigate the ability of weekly intra-articular injections of collagen tripeptide (Ctp) to prevent knee osteoarthritis (OA) compared with sodium hyaluronan (HA).
Methods: Thirty rabbits with anterior cruciate ligament (ACL) transection were randomly divided into three groups: Ctp, HA, and saline (control). All animals were administered the same amount of each reagent once weekly. Articular cartilages of the medial condyle of femur were examined by gross morphological and histopathological examination conducted at 5 (n=6) and 10 (n=4) weeks.
Results: The Ctp and HA injection groups tended to have improved gross morphological scores and exhibited preventive effects compared with control groups at 10 weeks after ACL transection. But the scores were not significantly different among the 3 groups. The overall means of histological grading scores were not significantly different among the 3 groups however, the score for the Ctp group had improved from 5 weeks to 10 weeks.
Conclusions: Intra-articular injections of Ctp may inhibit progression of knee OA, and further examination is needed to clarify the physical characteristics and regenerative functions of Ctp, and to determine the optimal dose and duration of Ctp injection therapy for the knee OA.

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    Buschke-Ollendorff syndrome (BOS) is recently shown to result from mutations in the LEMD3 gene. This study examined a 5-year-old boy with asymptomatic multiple flesh-colored round or oval cutaneous plaques on his abdomen and back. Skin biopsy specimen revealed increased amounts of collagen in the dermis extending into the subcutaneous fat. Radiographs of the long bones were normal. Physical examination on the other family members demonstrated that the proband’s father and the elder sister had similar skin plaques on their trunk. Radiographs of the long bones revealed osteopoikilosis in the father. These findings made a diagnosis of BOS. We performed a mutational analysis of the LEMD3 gene using genomic DNA extracted from peripheral blood leukocytes. Direct sequencing of all exons and intron/exon boundaries of the LEMD3 gene, identified a nucleotide change in the intron6/exon6 boundaries in all the affected family members. We discuss the possible molecular pathogenic mechanism of BOS in relation to the defect of LEMD3 function.

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    Gitelman's syndrome (GS) is considered to be a rare disorder. To assess the prevalence of GS in the Japanese general population and the relationships between mutations of related genes and blood pressure, we performed mutational analysis of the SLC12A3 gene on 1,567 subjects from Aomori Prefecture in northern Japan. Three GS mutations in SLC12A3, identified in the subjects with hypokalemia in a preliminary study were assessed by the TaqMan PCR method. We detected T180K, L849H and R919C missense mutations in 40, 49 and 57 subjects, respectively. The overall frequency of GS mutations was 8.9%. The mutant allele frequency of T180K, L849H and R919C was 1.3, 1.6 and 1.9%, respectively. GS mutant allele frequency in the 1,567 Japanese was more than 4.8%. In addition, subjects with L849H mutation had significantly lower systolic blood pressure when compared to subjects with wild-type SLC12A3 (121.8 ± 18.4 versus 127.8 ± 18.9 mmHg; P < 0.05). In conclusion, the present results suggest that the frequency of GS mutations is unexpectedly high, although GS is considered to be a rare disorder. The results also suggest that loss-of-function in the SLC12A3 via the L849H mutation reduces blood pressure, thereby contributing to resistance to hypertension.

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    Few studies have reported the time spent outdoors in patients undergoing long-term oxygen therapy (LTOT). Also, few have determined whether time spent outdoors was influenced by psychological impairments. The aim of the present study was to examine the usage of oxygen cylinders to assess the time spent outdoors of patients receiving LTOT, and to evaluate the prevalence of dementia and depressive states and determine the correlation between these disorders and time spent outdoors. Fifty-four LTOT patients were　enrolled in the present study, and dementia and depressive states were investigated using specific questionnaires. Among them, 23 patients were reassessed one year after the initial evaluation. There was a large variation in time spent outdoors among LTOT patients, and the median number was one hour per day. Measured by the Hasegawa Dementia Scale-Revised (HDS-R), dementia was observed in 41% of the patients. Depressive state, measured by the Self-Rating Depression Scale (SDS), was observed in 24%. There were no correlations between time spent outdoors and psychological impairments. The percentage of patients in depressive states was statistically higher in the 2nd assessment. More attention must be given to LTOT patients' usage of oxygen cylinders, and dementia and depressive state should be periodically assessed.

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    Ultraviolet (UV) radiation is one of the important etiologic factors for skin cancer. Pigmentation of the skin is the major photoprotective mechanism against UV radiation on human skin. Pigmentation depends on the function of melanocytes, which produces melanin and transfers melanosomes to surrounding keratinocytes. Endothelin-1 (ET-1), and stem cell factor (SCF) are cytokines secreted by UVB-exposed kerationcytes, playing pivotal roles in regulating the melanogenesis in normal human melanocytes (NHM). In this study, we demonstrated that treatment with ET-1 and/or SCF not only stimulated melanogenesis but also significantly suppressed the UV-induced cell death in NHM. In addition, we revealed that expression of heme oxygenase-1 (HO-1), an anti-oxidative protein, is up-regulated by ET-1 or SCF in NHM. Taken together, ET-1/SCF, secreted by UV-irradiated keratinocytes, increases HO-1 expression, thereby protecting melanocytes from UV-induced apoptosis, and stimulates melanin synthesis in melanocytes to protect keratinocytes from UV-induced cell damage. It can be regarded as the interaction of photoprotective effect between keratinocyte and melanocyte.

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    We analyzed the prevalence of irritable bowel syndrome (IBS) and its relation to lifestyle and depression quotient in a general population in Japan. Seven-hundred and sixty-three adults (288 males and 475 females) were enrolled in a cross-sectional study of the Iwaki Health Promotion Project in 2008. Self-questionnaires regarding smoking habit, alcohol consumption, exercise habit, dietary habit and depression quotient (Center for Epidemiologic Studies Depression Scale) were given out. Each participant was checked for IBS according to the Rome II criteria. The odds ratios for IBS prevalence were calculated using a multiple logistic regression analysis with age, body mass index, depression quotient, exercise habit, smoking habit, alcohol consumption and five dietary patterns as the explanatory variables. In genders, depression quotient showed high odds ratios for the incidence of IBS. Alcohol consumption showed a significantly high odds ratio for the incidence of IBS in males and the Japanese traditional dietary pattern had a significantly lower odds ratio in females. In conclusion, in order to prevent the occurrence of IBS in a general population in Japan, abstinence from alcohol for men, the Japanese traditional dietary pattern for women and mental management in both genders may be recommend.

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    Raf kinase inhibitor protein (RKIP) has been demonstrated to bind to Raf-1 and mitogen-activated protein kinase kinase (MEK) and to inhibit the mitogen-activated protein kinase (MAPK) signaling pathway. Recently, we have discovered that introduction of the RKIP gene into human keratinocytes induces differentiation. In this study, we first examined expression of RKIP in the mouse epidermis in vivo and found that RKIP was expressed in all keratinocyte layers. However, western blot analysis clearly showed that differentiated keratinocytes expressed more RKIP than undifferentiated keratinocytes. These data indicated that RKIP expression in the mouse epidermis increased with keratinocyte differentiation. As 1α,25-dihydoxyvitamin D₃(1,25(OH)₂D₃) suppresses keratinocyte proliferation and promotes differentiation, we next examined the effect of 1,25(OH)₂D₃ on RKIP expression and found that 1,25(OH)₂D₃ increased mRNA and protein expression of RKIP in cultured mouse keratinocytes. These results suggest that 1,25(OH)₂D₃-induced keratinocyte differentiation may be mediated by induction of RKIP expression.

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Introduction: The employment of laparoscopic resection for the treatment of colorectal cancer has been expanding rapidly. However, its indication is still on debate. We have been actively employing laparoscope-assisted colectomy (LAC) for patients with early colorectal cancer. Here we retrospectively review the 71 cases of early colorectal cancer treated with LAC and analyzed the initial institutional surgical outcome.
Results: LAC was indicated as an additional surgical resection after endoscopic treatment in 27 cases, while it was employed as a definitive non-endoscopic treatment in 44 cases. Mean operative time was 163 min, and mean blood loss was 57 ml. Complications were encountered in 8 cases (11.3%). Advanced lesions invading to the muscularis propria or the serosa were more included in the group initially treated with LAC alone (p=0.04). The reasons for additional LAC were the depth of submucosal invasion >1000μm in 15 cases and lymphatic or microvascular invasion in 5 cases. Lymph node metastases were detected pathologically in 9 patients, in which one suffered relapse after surgery.
Conclusion: Implementation of LAC for early colorectal cancer seems an acceptable strategy in terms of both radicality and less invasiveness. Cooperation between endoscopists and laparoscopic surgeons is important to apply LAC appropriately for colorectal cancer.

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INTRODUCTION: Pylorus-preserving gastrectomy (PPG), which had been developed in 1960s, has been reappraised for years and now accepted as a type of function-preserving limited surgery for early-stage gastric cancer in the latest version of the Japanese guideline for the treatment of gastric cancer. Laparoscopy-assisted pylorus-preserving gastrectomy (LAPPG) may compensate for the weak points of PPG in magnifying the view of many anatomic tissues around the stomach. The aim of this study was to investigate the usefulness of LAPPG regarding the early surgical outcomes, as compared with those of laparoscopy-assisted distal gastrectomy (LADG), which does not preserve the pylorus and involves resection of the suprapyloric lymph nodes.
METHODS: Ninety six patients diagnosed as having gastric cancer of cT1N0 underwent either LADG (n=66) or LAPPG (n=30). The patient demographics and the early surgical outcomes were evaluated retrospectively. The quality of lymph node dissection in LAPPG was also assessed pathologically.
RESULTS: Among 96 patients preoperatively diagnosed as cT1, pT1 was 88 cases and pT2 in 8, 91.7 % of diagnostic accuracy. There were no differences in patient demographics, operative time, blood loss, the number of dissected lymph nodes, postoperative morbidity and length of hospitalization. Pathologically, the number of dissected lymph nodes at No. 3, 4, 6 were equal between the two groups. Among our LADG cases, 35 (53%) were lesions confined to the mucosa with a distance between the pylorus and the anal margin of the tumor < 4 cm.
CONCLUSIONS: Our initial experience suggests that LAPPG can be performed with acceptable quality of lymph node dissection and early surgical outcome. Because LAPPG was thought to be applied for about a half of our LADG cases according to the new guideline, LAPPG is expected to be indicated for more cases with early gastric cancer as a function-preserving limited surgery.

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    The purpose of this study is to reveal the actual conditions of dyschezia as recognized by postoperative rectal cancer patients and their self-care, as well as the subjective QOL (Schedule for the Evaluation of Individual Quality of Life-Direct Weighting: SEIQoL-DW), and to obtain suggestions for the nursing intervention for improving the self-care of dyschezia and QOL. The subjects were 88 patients (age: 62.2 ± 9.3 years), consisting of 33 and 55 patients that received intersphincteric resection (ISR) and low anterior resection (LAR), respectively. The mean of the SEIQoL-DW index was 66.7 ± 15.3 for ISR and 63.8 ± 14.8 for LAR, showing no significant difference. The dyschezia was grouped into seven categories such as [frequent defecation], [irregular number of defecations], [defecation on oral drug administration], [frequent nocturnal defecation], [fecal incontinence], and [anal pain]. The proportions of [irregular number of defecations], [frequent nocturnal defecation], and [fecal incontinence] were significantly higher for ISR than LAR. The self-care of dyschezia can be summarized into eleven categories such as [washing anus], [applying diapers and pads], [controlling dietary intake], and [controlling defecation]. In conclusion, it is important to understand in detail the fecal control, local anal care, food content, and intake method as nursing interventions using a checklist, and to instruct the patients individually in cooperation with physicians and physical therapists.

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    Thrombotic thrombocytopenic purpura (TTP) is a life-threatening illness associated with cardiovascular surgery, infection and medications. We report a case of a 77-year-old female patient with acute myocardial infarction (AMI) treated with percutaneous coronary intervention and suffered TTP immediately afterwards. This was successfully treated with plasma exchanges. Differential diagnosis of the thrombocytopenia was important and assays for the activities of von Willebrand Factor-cleaving protease, its inhibitor and heparin-induced thrombocytopenia (HIT) antibody were helpful to differentiate TTP from other conditions, including HIT and disseminated intravascular coagulation. Intensivists should be aware of an atypical presentation of TTP associated with AMI.

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