The
Clock gene is a core component of the circadian clock in mammals. We show here that serum levels of triglyceride and free fatty acid were significantly lower in circadian
Clock mutant ICR than in ...wild-type control mice, whereas total cholesterol and glucose levels did not differ. Moreover, an increase in body weight induced by a high-fat diet was attenuated in homozygous
Clock mutant mice. We also found that dietary fat absorption was extremely impaired in
Clock mutant mice. Circadian expressions of cholecystokinin-A (CCK-A) receptor and lipase mRNAs were damped in the pancreas of
Clock mutant mice. We therefore showed that a
Clock mutation attenuates obesity induced by a high-fat diet in mice with an ICR background through impaired dietary fat absorption. Our results suggest that circadian clock molecules play an important role in lipid homeostasis in mammals.
CLOCK is a positive component of a transcription/translation-based negative feedback loop of the central circadian oscillator in the suprachiasmatic nucleus in mammals. To examine CLOCK-regulated ...circadian transcription in peripheral tissues, we performed microarray analyses using liver RNA isolated from Clock mutant mice. We also compared expression profiles with those of Cryptochromes (Cry1 and Cry2) double knockout mice. We identified more than 100 genes that fluctuated from day to night and of which expression levels were decreased in Clock mutant mice. In Cry-deficient mice, the expression levels of most CLOCK-regulated genes were elevated to the upper range of normal oscillation. Most of the screened genes had a CLOCK/BMAL1 binding site (E box) in the 5′-flanking region. We found that CLOCK was absolutely concerned with the circadian transcription of one type of liver genes (such as DBP, TEF, and Usp2) and partially with another (such as mPer1, mPer2, mDec1, Nocturnin, P450 oxidoreductase, and FKBP51) because the latter were damped but remained rhythmic in the mutant mice. Our results showed that CLOCK and CRY proteins are involved in the transcriptional regulation of many circadian output genes in the mouse liver. In addition to being a core component of the negative feedback loop that drives the circadian oscillator, CLOCK also appears to be involved in various physiological functions such as cell cycle, lipid metabolism, immune functions, and proteolysis in peripheral tissues.
Psychological stress or life events might significantly decrease neutrophil function in elderly individuals and lead to infectious diseases. However, relationships between these factors have not been ...examined in detail.We investigated the relationships between neutrophil function measured using the nitroblue tetrazolium (NBT) reduction test and measurements of psychological stress and life events among 81 men aged over 60 years.
The numbers and scores for life events were significantly higher (p < 0.01, respectively) in a group with values reflecting phagocytosis below the median than in a control group.
Chronic psychological stress due to life events decreases neutrophil functions among elderly men.
The application of carbon nanotubes (CNTs) as biomaterials is of wide interest, and studies examining their application in medicine have had considerable significance. Biological safety is the most ...important factor when considering the clinical application of CNTs as biomaterials, and various toxicity evaluations are required. Among these evaluations, carcinogenicity should be examined with the highest priority; however, no report using transgenic mice to evaluate the carcinogenicity of CNTs has been published to date. Here, we performed a carcinogenicity test by implanting multi-walled CNTs (MWCNTs) into the subcutaneous tissue of rasH2 mice, using the carbon black present in black tattoo ink as a reference material for safety. The rasH2 mice did not develop neoplasms after being injected with MWCNTs; instead, MWCNTs showed lower carcinogenicity than carbon black. Such evaluations should facilitate the clinical application and development of CNTs for use in important medical fields.
The purpose of tumorigenicity testing, as applied not only to cell substrates used for viral vaccine manufacture but also stem cells used for cell-based therapy, is to discriminate between cells that ...have the capacity to form tumors and cells that do not. Therefore, tumorigenicity testing is essential in assessing the safety of these biological materials. Recently developed NOD/Shi-scid IL2Rgnull (NOG) mice have been shown to be superior to NOD/Shi-scid (SCID) mice for xenotransplantation of both normal and cancerous cells. To select a suitable mouse strain as a xenogenic host for tumorigenicity testing, we compared the susceptibility of NOG (T, B, and NK cell-defective), SCID (T and B cell-defective), and the traditionally used nude (T cell-defective) mice to tumor formation from xenotransplanted HeLa S3 cells. When 104 HeLa S3 cells were subcutaneously inoculated into the flanks of these mice, the tumor incidence on day 22 was 10/10 (100%) in NOG, 2/10 (20%) in SCID, and 0/10 (0%) in nude mice. The subcutaneous tumors formed reproducibly and semiquantitatively in a dose-dependent manner. Unexpectedly, half of the NOG mice (5/10) that had been inoculated with a mere 101 HeLa S3 cells formed progressively growing subcutaneous tumors on day 78. We confirmed that the engrafted tumors originated from inoculated HeLa S3 cells by immunohistochemical staining with anti-HLA antibodies. These data suggest that NOG mice may be the best choice as a suitable strain for testing tumorigenicity.
Background. Pulmonary tumor embolism is difficult to diagnose before death. However, a few cases have suggested the possibility of improvement in the antemortem diagnosis and prognosis of pulmonary ...tumor embolism. It is therefore important to perform a biopsy if pulmonary tumor embolism is suspected. Case. A 55-year-old woman was referred to our department due to chronic cough and dyspnea, which had been worsening over a period of several months. She was admitted after chest CT showed bilateral diffuse pulmonary ground glass appearance. This was followed by a transbronchial lung biopsy that confirmed adenocarcinoma. Furthermore, the coexistence of carcinoma and pulmonary hypertension was identified. Thus, she was clinically diagnosed with pulmonary tumor embolism. Chemotherapy was planned, but she couldn't receive the treatment as her symptoms progressed rapidly leading to her death on the 18th day after admission. The autopsy report of the patient revealed gastric cancer with pulmonary tumor embolism. Conclusion. It is important to diagnose pulmonary tumor embolism pathologically, as this might help to improve the prognosis. We therefore concluded that transbronchial lung biopsy might be useful for the diagnosis of pulmonary tumor embolism.
Background. Eosinophilic pneumonia following lung resection is a rare occurrence. Case 1. The first case was a 69-year-old man with non-small cell lung cancer who underwent right lower lobectomy. On ...postoperative day 4, CT scan showed reticular ground glass opacity in the right middle lobe, and bronchoalveolar lavage (BAL) revealed an increase in the number of eosinophils. After methylprednisolone pulse therapy on postoperative day 9, the patient showed immediate improvement in clinical and radiologic abnormalities. Case 2. The second case was a 66-year-old man with small cell lung cancer who underwent wedge resection of the left upper lobe. On postoperative day 12, the patient experienced shortness of breath on effort; subsequently, BAL revealed an increase in the number of eosinophils. Oral administration of prednisolone resulted in improvement of the radiographical findings. Conclusion. BAL is useful for the diagnosis of respiratory dysfunction in patients with interstitial pneumonia following surgery.
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