Time-course expression profiles of hair cycle-associated genes in male mini rats after depilation of telogen-phase hairs.

Jcl:WistarTGN(ARGHGEN)1Nts rat (Mini rat) is a growth hormone (GH)-deficient transgenic rat. The hair cycle in the dorsal skin of male Mini rats enters a long-lasting telogen phase after eights weeks of age, but depilation can induce a transient hair cycle again. In this study, a time-course profiling of genes expression was done on the dorsal skin of male Mini rats along the progression of depilation-induced hair cycle using DNA microarray analysis. As a result, 1,215 probe sets including 1,171 hair cycle-related ones showed more than 3-fold changes in expression compared with that in before-depilation telogen phase. The present data will contribute to elucidating the mechanisms of hair cycle regulation and should lead to the identification of novel molecular targets for hair growth and/or depilation agents

Development of Calorie Restriction Mimetics as Therapeutics for Obesity, Diabetes, Inflammatory and Neurodegenerative Diseases

Calorie restriction (CR) is the most robust intervention that decreases morbidity and mortality, and thereby increases the lifespan of many organisms. Although the signaling pathways involved in the beneficial effects of CR are not yet fully understood. Several candidate pathways and key molecules have been identified. The effects of CR are highly conserved from lower organisms such as yeast to higher mammals such as rodents and monkeys. Recent studies have also demonstrated beneficial effects of CR in humans, although we need much longer studies to evaluate whether CR also increases the lifespan of humans. In reality, it is difficult for us to conduct CR interventions in humans because the subjects must be kept in a state of hunger and the duration of this state needed to achieve a clinically meaningful effect is still unknown. Thus, research in this field is focusing on the development of molecules that mimic the beneficial effects of CR without reducing food intake. Some of these candidate molecules include plant-derived functional chemicals (phyto-chemicals), synthetic small molecules, and endocrine molecules such as adipokines. Several studies have already shown that this research field may yield novel drugs for the treatment of age-related diseases such as diabetes. In this article, we describe the target pathways, candidate molecules, and strategies to develop CR mimetics

Protein Reporter Bioassay Systems for the Phenotypic Screening of Candidate Drugs: A Mouse Platform for Anti-Aging Drug Screening

Recent drug discovery efforts have utilized high throughput screening (HTS) of large chemical libraries to identify compounds that modify the activity of discrete molecular targets. The molecular target approach to drug screening is widely used in the pharmaceutical and biotechnology industries, because of the amount of knowledge now available regarding protein structure that has been obtained by computer simulation. The molecular target approach requires that the structure of target molecules, and an understanding of their physiological functions, is known. This approach to drug discovery may, however, limit the identification of novel drugs. As an alternative, the phenotypic- or pathway-screening approach to drug discovery is gaining popularity, particularly in the academic sector. This approach not only provides the opportunity to identify promising drug candidates, but also enables novel information regarding biological pathways to be unveiled. Reporter assays are a powerful tool for the phenotypic screening of compound libraries. Of the various reporter genes that can be used in such assays, those encoding secreted proteins enable the screening of hit molecules in both living cells and animals. Cell- and animal-based screens enable simultaneous evaluation of drug metabolism or toxicity with biological activity. Therefore, drug candidates identified in these screens may have increased biological efficacy and a lower risk of side effects in humans. In this article, we review the reporter bioassay systems available for phenotypic drug discovery

The Relation of Prostate Tissue Protein Content, Nd : YAG Laser Transmissibility and Thermal Effect on Prostatic Hyperplasia

As our society ages, safe and minimally invasive treatment for the frequent occurrence of prostatic hyperplasia have been sought. We have performed prostatic hightemperature treatment for prostatic hyperplasia with the Prostalase using neodymium : yattriumaluminum garnet (Nd : YAG) laser for patients suffering from a bladder outlet obstruction secondary to benign prostatic hyperplasia (BPH). We used agars which included various densities of protein and skim milk as test materials to determine whether the exothermic mechanism of the Nd : YAG laser irradiation has an effect on protein molecules. By measuring the temperature inside the test materials and the irradiation transmissibility, we verified that in tissues with the same degree of color, the higher the protein content, the stronger the exothermic action of the Nd : YAG laser. In addition, in three human prostates obtained through pathological autopsy, the measurement of the protein content and the temperature inside the prostatic tissue in which prostatic thermal treatment had been performed showed that the exothermic action of the Nd : YAG laser varied according to the protein content: the higher the protein content, the stronger was the exothermic action. The present findings suggest that the temperature inside prostatic tissue reaches at least 60-65邃・with intissues with a protein content more than 23g/100g

The Role of Neuropeptide Y in Adipocyte-Macrophage Crosstalk during High Fat Diet-Induced Adipose Inflammation and Liver Steatosis

Obesity is associated with an increased risk of non-alcoholic fatty liver disease (NAFLD), which is initiated by adipocyte-macrophage crosstalk. Among the possible molecules regulating this crosstalk, we focused on neuropeptide Y (NPY), which is known to be involved in hypothalamic appetite and adipose tissue inflammation and metabolism. In this study, the NPY−/− mice showed a marked decrease in body weight and adiposity, and lower free fatty acid and adipose inflammation without food intake alteration during a high fat diet (HFD). Moreover, NPY deficiency increased the thermogenic genes expression in brown adipose tissue. Notably, NPY-mRNA expression was upregulated in macrophages from the HFD mice compared to that from the mice on a standard diet. The NPY-mRNA expression also positively correlated with the liver mass/body weight ratio. NPY deletion alleviated HFD-induced adipose inflammation and liver steatosis. Hence, our findings point toward a novel intracellular mechanism of NPY in the regulation of adipocyte-macrophage crosstalk and highlight NPY antagonism as a promising target for therapeutic approaches against obesity and NAFLD

Intussusception secondary to endometriosis of the cecum

INTRODUCTION Intussusception in adults is a rare cause of bowel obstruction. Endometriosis of the bowel is also a rare entity that can be the cause of bowel obstruction. Here, we report a rare case of intussusception secondary to endometriosis of the cecum.PRESENTATION OF CASE A 40-year-old woman presented to the hospital with a one-week history of intermittent epigastric pain. On physical examination, there was a soft, round non-tender palpable mass in the right flank and abdominal computed tomography scan revealed an intussusception. We made the diagnosis of ileo-colic intussusception and performed ileocecal resection. The surgical specimen revealed a round submucosal cystic mass in the cecum and the histology showed endometriosis of the cecum.DISCUSSION Intussusception in adults is a rare entity present in just 1% of all patients with bowel obstruction, and 5% of all intussusceptions. In general, intussusception in adults has a pathologic lesion as the lead point and the lesion is a malignancy in 20-50% of the cases. Thus, the treatment of an intussusception in adults should be operative. Endometriosis of the bowel is a rare cause of intussusception. Small endometriosis lesions of the bowel are unlikely to cause symptoms; however, in patients presenting with bowel obstruction, urgent treatment is indicated.CONCLUSION Intussusception in an adult is a rare cause of bowel obstruction and intussusception caused by endometriosis is also rare. Although rare, the diagnosis of endometriosis as a cause of intussusception must be considered as part of the differential diagnosis

Adamantinoma of the Tibia. - Report of a Case with Findings of Ultrastructural and Immunohistochemical Studies,

A case of tibial adamantinoma in a one-year and ten-month old girl is reported. She had gait disturbance and her roentogenogram showed a well circumscribed radiolucent area in the tibia. Light microscopic examination showed the epithelial component of nests and pseudoglandular arrays in the loose fibrous connective tissue. We finally diagnsed the tumor as adamantinoma of the tibia based on roentogenographical and histological findings. Moreover, the nature of the neoplastic cells was studied by the immunohistochemical and electron microscopic methods. The adamantinoma is regarded as a unique neoplasm capable of differen - tiating into epithelial elements as well as mesenchymal ones . Detection of epithelial component is important to differentiate from similar disorders. The fibrous dysplasia- like lesion in stroma is interpreted as a part of the spectrum of mesenchymal differentiation

Papillary Adenoma of Type 2 Pneumocytes in the Lung

Recent developments in radiologic imaging and thoracoscopic excision techniques have increased the possibility of encountering small, benign or premalignant tumors in the lung. In this report, we describe a rare case of papillary adenoma of type 2 pneumocytes. A 51-year-old Japanese woman was hospitalized following a traffic accident. Helical CT scan of the chest incidentally detected a nodular ground-glass opacity measuring 8 mm in diameter at the subpleural region of left lung. The nodule was thoracoscopically resected out. Light microscopic examination demonstrated a noninfiltrative tumor consisting of cuboidal cells covering fibrovascular cores; thus, the tumor exhibited a branching papillary appearance. The cuboidal cells showed little nuclear atypia. Mitotic figures, necrosis, and intercellular mucin were absent. The cytoplasm was immunohistochemically stained for surfactant apoprotein A and cytokeratin, though not for carcinoembryonic antigen (CEA), epithelial membrane antigen (EMA), or S100 protein. The morphologic and immunohistochemical findings fulfilled the criteria of papillary adenoma of type 2 pneumocytes