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Accumulating evidence suggests that kisspeptin-GPR54 signaling is indispensable for gonadotropin-releasing hormone (GnRH)/gonadotropin secretion and consequent reproductive functions in mammals. Conventional Kiss1 knockout (KO) mice and rats are reported to be infertile. To date, however, no study has investigated the effect of inducible central Kiss1 KO/knockdown on pulsatile gonadotropin release in male mammals. Here we report an in vivo analysis of inducible conditional Kiss1 knockdown male mice. The mice were generated by a bilateral injections of either adeno-associated virus (AAV) vectors driving Cre recombinase (AAV-Cre) or AAV vectors driving GFP (AAV-GFP, control) into the hypothalamic arcuate nucleus (ARC) of Kiss1-floxed male mice, in which exon 3 of the Kiss1 gene were floxed with loxP sites. Four weeks after the AAV-Cre injection, the mice showed a profound decrease in the both number of ARC Kiss1-expressing cells and the luteinizing hormone (LH) pulse frequency. Interestingly, pulsatile LH secretion was apparent 8 weeks after the AAV-Cre injection despite the suppression of ARC Kiss1 expression. The control Kiss1-floxed mice infected with AAV-GFP showed apparent LH pulses and Kiss1 expression in the ARC at both 4 and 8 weeks after the AAV-GFP injection. These results with an inducible conditional Kiss1 knockdown in the ARC of male mice suggest that ARC kisspeptin neurons are responsible for pulsatile LH secretion in male mice, and indicate the possibility of a compensatory mechanism that restores GnRH/LH pulse generation.

Hiroto Narimatsu,1,2 Masahiko Sakaguchi,1 Sho Nakamura,1,2 Kayoko Katayama1 1Cancer Prevention & Control Division, Kanagawa Cancer Center Research Institute, Yokohama 241-8515, Japan; 2Graduate School of Health Innovation, Kanagawa University of Human Services, Kawasaki, Kanagawa 210-0821, JapanCorrespondence: Hiroto NarimatsuKanagawa Cancer Center Research Institute, 2-3-2 Nakao Asahi-ku, Yokohama 241-8515, JapanTel +81-45-520-2222 Ext 4022Fax +81-45-520-2216Email hiroto-narimatsu@umin.orgPurpose: The distribution of patients with hematological malignancies is expected to change markedly in the future due to aging of the Japanese population. We assessed the expected incidence rates of leukemia, malignant lymphoma, and multiple myeloma using national population estimates and data from the Kanagawa Cancer Registry.Patients and Methods: To evaluate the effects of community aging, we compared expected future incidences of hematological malignancies in Kanagawa with other three areas, namely the Yamagata, Osaka, and Nagasaki prefectures, which have different populations and predicted aging rates.Results: The total number of patients newly diagnosed with hematological malignancy in Kanagawa in 2010 was 1970. This was predicted to increase to 2581 by 2025 and to 2712 by 2040. Trends were very similar for all three hematological malignancies. These incidence rates were predicted to increase continuously in patients aged ≥ 65 years from 2010 to 2040, with a 169% increase in leukemia, a 167% increase in malignant lymphoma, and a 169% increase in multiple myeloma. A continuous increase in the population aged ≥ 65 years was also noted in the other three prefectures.Conclusion: The distribution demographic of patients with hematological malignancies is expected to change in the future as the number of elderly patients increases.Keywords: leukemia, myeloma, lymphoma, aging, hematopoietic stem cell transplantation

Short-chain fatty acids (SCFAs) are the main source of energy for postweaning ruminants. The monocarboxylic acid transporters, MCT1 and MCT4, are thought to contribute to the absorption of SCFAs from the surface of the rumen following weaning. The present study measured changes in MCT1 and MCT4 expression in ruminal epithelial cells isolated from male preweaning (22 to 34 d old, n = 6) and postweaning (55 to 58 d old, n = 8) calves after euthanasia and sought to examine whether SCFAs stimulate the expression of these transporters. In the current study, cluster of differentiation 147 (CD147) gene expression in the rumen was also investigated since CD147 has been considered to act as ancillary protein for MCT1 and MCT4 to express their correct function. The gene expression levels of MCT1, MCT4, and CD147 in the rumen were found to be significantly higher in postweaning calves than in preweaning calves. Strong MCT1 immunoreactivity was detected in both the stratum basale (SB) and the stratum spinosum (SS) in postweaning ruminal epithelium. Expression of MCT1 in preweaning calves was localized to a specific region of the SB and of the SS. MCT4-immunopositive cells were detected in the stratum corneum (SC) of the ruminal epithelium in postweaning calves. However, only a low level of signal was detected in the SC of preweaning animals. Furthermore, in vitro experiments, ruminal epithelial cells were incubated for 24 h with acetate (0.04, 0.4, and 4 mM), propionate (0.2, 2, and 20 mM), butyrate (0.1, 1, and 10 mM), or β-hydroxybutyrate (BHBA; 0.1, 1, and 10 mM), respectively. Both propionate and butyrate induced an increase in the gene expression levels of MCT4 and CD147, but did not affect MCT1 gene expression. There are no significant effects of acetate and BHBA treatment on these gene expressions. Taken together, these results suggest that an increase in MCT4 and CD147 gene expression in the ruminal epithelium of postweaning calves is likely to be due to the effects of propionate and butyrate derived from a solid-based diet, which may contribute to ruminal development following weaning.

Sho Nakamura, Tadahisa Fukui, Shuhei Suzuki, Hiroyuki Takeda, Kaname Watanabe, Takashi Yoshioka Department of Clinical Oncology, Yamagata University Faculty of Medicine, Yamagata, Japan Abstract: Bone marrow metastasis is a rare consequence of colorectal cancer that results in a poor prognosis; few reports describe a favorable response to doublet chemotherapy combined with targeted therapy, which is currently the standard treatment. We experienced a case where anti-epidermal growth factor receptor (EGFR) antibody produced a marked anti-tumor response to bone marrow metastasis that led to long-term survival. A 51-year-old man was diagnosed with a primary KRAS-wildtype rectal cancer with multiple metastases, including the bone marrow. Disease control was achieved for 10.8 months following chemotherapy with a modified FOLFOX6 regimen combined with an anti-EGFR antibody. He died of cancer 22.7 and 16.6 months after disease onset and first-line chemotherapy, respectively. This case shows that early tumor shrinkage and deepness of response to the anti-EGFR antibody were observed even in a patient with bone marrow metastasis. Anti-EGFR antibody therapy should therefore be considered even when a patient’s medical condition appears to be poor owing to bone marrow metastasis. Moreover, tumors that are likely to be sensitive to chemotherapy, such as RAS-wildtype colorectal cancers, can be considered for anti-EGFR antibody therapy even if the patient is considered unfit for chemotherapy. Keywords: colorectal cancer, anti-epidermal growth factor receptor antibody, molecular targeted therapies, disseminated intravascular coagulation, standard of care

Effects of Korean red pepper on lipid metabolism were investigated using the rats. The red pepper was orally administrated as a part of diet. Daily intake of the red pepper decreased plasma triglyceride and deposit fat. The red pepper taken as a diet influences lipid metabolism and may have preventive effects on lifestyle-related disease.

蓄尿型人工膀胱(リザーバー, R群)12例, 回腸導管術10例(C群)で術施行後2ヵ月で感染性尿路結石の危険因子および予防因子を調べた。両群間に危険因子および複数の危険因子の陽性率に有意差がなかった。しかしR群の4例は複数の危険因子を持ってリザーバー内に結石を生じたが, C群ではなかった。R群では1個の危険因子より複数の危険因子を持つものの結石発生率は有意に高かった。56歳の回腸導管術の症例を提示した, Urinary risk factors and preventive factors for infectious calcium (Ca) urolithiasis formation, such as citrate, oxalate, Ca, phosphate, magnesium, and uric acid were examined more than 2 months after performing a urinary reservoir in 12 patients (R group) and ileal conduit in 10 patients (C group). There was no difference in the positive rate of risk factors between the two groups and also no difference in the positive rate of more than two risk factors between the two groups. Although four patients with more than two risk factors in the R group suffered from reservoir stones all of which included Ca-urolithiasis, none in the C group did. In the R group, the incidence of stone formation in patients with 2 or more risk factors was significantly higher than those in patients with 1 or no risk factor. In conclusion, the urinary reservoir operation should not be carried out in patients with more than two risk factors for urolithiasis formation, and urinary risk factors should be examined before reservoir operation.

In order to determine clinical effect of fosfomycin Na(FOM) in urinary tract infections caused by Pseudomonas and Proteus, a comparative study was carried out on patients with chronic complicated urinary tract infections, using sulbenicillin Na(SB-PC) as an active control drug. Both FOM and SB-PC were administered through intravenous infusions in the same dosage of 2 g twice daily for a period of 5 days, and comparisons were made in terms of clinical and bacteriological effects and adverse reactions with a single blind technique. The results obtained were as follows: 1. There was no significant difference in global clinical effects between FOM and SB-PC. 2. With respect to clinical effects as classified by the types of disease, FOM was found to be superior with significant difference in the group of low urinary tract infection. 3. Determinations of MICs of FOM and SB-PC for the isolated organisms revealed higher sensitivity of FOM with significant difference, although no statistically significant difference was seen in terms of disappearance of bacteriuria between the two drugs. 4. There was no significant difference in frequencies of adverse reactions between FOM and SB-PC. All the observed reactions were mild in nature and occurred only in a small number of cases. Therefore, it was concluded that both drugs are of sufficient value to be applied clinically.