The effect of peroxisome proliferator-activated receptor-gamma ligand on urological cancer cells

Peroxisome proliferator activator-receptor (PPAR)-gamma ligand induces growth arrest of cancer cells through apoptosis. In this study, we examined the effects of PPAR-gamma inhibitors on cell proliferation in renal cell carcinoma (RCC), bladder tumor (BT), and prostatic carcinoma (PC) cell lines. We investigated the inhibitory effect of PPAR-gamma ligands, troglitazone and 15-deoxy-Delta12,14-prostaglandin J2 (15dPGJ2) on RCC, BT and PC-derived cell lines using MTT assay and Hoechst staining. PPAR-gamma ligands (troglitazone and 15dPGJ2) induced the reduction of cell viability with the half-maximal concentration of growth inhibition of RCC, BT, and PC cell lines. Furthermore, counting cells at days 1, 2 and 3, clearly showed marked inhibition of cell proliferation using troglitazone and 15dPGJ2. All PPAR-gamma inhibitors stopped the growth of all RCC, BT and PC cells. Cells treated with PPAR-gamma inhibitors showed chromatin condensation, cellular shrinkage, small membrane-bound bodies (apoptotic bodies), and cytoplasmic condensation. These cellular changes were typically redundant characteristics of apoptosis. PPAR-gamma ligands may mediate potent antiproliferative effects against RCC, BT and PC cells through differentiation. Thus, PPAR-gamma may become a new target in treatment of urological tumors.     

Practical application of nutritional assessment protein and inflammatory marker in the nutrition support team (NST)

Recently nutrition support team (NST) has been established for the purpose of prevention of complications which are caused by nutrition disorders and reduction of the medical expenses. Although physical examinations and blood biochemical data had been used as the indexes evaluating nutritional of patients, they were not suitable for the evaluation for the short-term in-patient. On the contrary, serum albumin (ALB) has been wildly used as a nutritional marker. However, it is impossible to evaluate nutrition state for the short-term in-patient and acute phase disease patient accurately, because the plasma half-life is 21 days and it takes long time to detect the change in nutritional state by its value. Rapid turnover proteins (RTP), whose plasma half-life is shorter, has paid attention to evaluate nutritional state for the short-term in-patients and acute phase disease patients. Although, prognostic inflammatory and nutritional index (PINI) was considered as a useful maker for evaluating inflammatory and nutritional states using the concentrations of transthyretin (TTR), a RTP, alpha1-acid glycoprotein (alpha1-AG), a chronic inflammation marker, C reactive protein (CRP), a acute inflammation marker, and ALB, However, it has several pitfalls. We newly made serum amyloid A (SAA) index using SAA instead of CRP. When we compared SAA index with PINI in many diseases, it turned out that SAA index became a more effective index which reflected the patient condition than did PINI. As for this index, it is expected to be used by NST while further alternation may be needed.     

Retinoblastoma protein prevents staurosporine-induced cell death in a retinoblastoma-defective human glioma cell line.

OBJECTIVE: To investigate the mechanism of staurosporine-induced glioma cell death and cell cycle arrest using adenovirus-mediated gene transfection, as well as the function of retinoblastoma (Rb) and genetic instability induced by staurosporine. METHODS: Cell cycle regulation, cell death and nuclear abnormalities induced by staurosporine were examined using an adenovirus vector expressing Rb, p16 or p21 genes in human glioma cell lines. RESULTS: The Rb-defective SF-539 cell line was resistant to staurosporine compared with cell lines expressing intact Rb. SF-539 glioma cells exposed to staurosporine became multinucleated and then died. Multinucleation was prevented in SF-539 cells transfected with the Rb gene, thus decreasing the death rate of these cells. CONCLUSIONS: These results imply that enforced Rb expression protects cells from genomic instability induced by staurosporine regardless of its upstream molecular effects.     

Use of a high-throughput umu-microplate test system for rapid detection of genotoxicity produced by mutagenic carcinogens and airborne particulate matter

In the present study, we developed a rapid umu-microplate test system that uses the nitroreductase- and O-acetyltransferase-overproducing Salmonella typhimurium strain NM3009 and the O-acetyltransferase-overproducing S. typhimurium strain NM2009 to detect genotoxic activity in small volume samples. The assay was used to test the genotoxicity of several standard mutagens and environmental samples. Exponentially growing cultures of NM3009, NM2009, and the parental strain TA1535/pSK1002 were incubated in 96-well microplates with test chemicals both in the presence and in the absence of rat liver S9. The relative beta-galactosidase activities were then determined colorimetrically using either chlorophenol red-beta-D-galactopyranoside (CPRG) or O-nitrophenyl-beta-D-galactopyranoside (ONPG) as a measure of umuC gene induction activity. The sensitivities of NM3009 without S9 mix and NM2009 with S9 mix to nitroarenes and aromatic amines were up to 24- to 75-fold higher than those of the parent strain. Induction of umuC gene expression was detected more readily with CPRG than ONPG. The umu-microplate assay also detected genotoxicity in organic extracts of particulate matter from air samples collected in Osaka City, Japan. The pattern of the responses suggested that the genotoxic activity of the particulate extract was due primarily to nitrated polycyclic aromatic hydrocarbons. Our results indicate that the umu-microplate assay may be a useful way of carrying out rapid screens for genotoxicity in small-volume environmental samples.     

Evidence of the monoclonal composition of human endometrial epithelial glands and mosaic pattern of clonal distribution in luminal epithelium

The endometrium is a highly regenerative tissue that plays a crucial role in implantation. We examined the clonal constitution of glandular cells as well as the luminal epithelium of this unique tissue. Using collagenase-based digestion techniques with microscopic manipulation, we isolated individual human endometrial glands and examined their clonality using a polymerase chain reaction-based assay for nonrandom X chromosome inactivation with an X-linked androgen receptor gene. Most of the glands analyzed were composed of monoclonal populations of epithelial cells and one of the glands exhibited a loss of heterogeneity in the androgen receptor gene. In addition, adjacent glands within a 1-mm(2) area shared clonality, suggesting that clonality of the luminal epithelium is regionally defined. The clonality of endometrium was further confirmed in a study of female mice that harbor the green fluorescent protein gene on either the maternal or paternal X chromosome. Fluorescent microscopy of uterine sections revealed that individual endometrial glands consisted completely of either fluorescent or nonfluorescent cells and that the surface epithelium exhibited a clear boundary between these cell types. These findings suggest that single or multiple stem cells with uniform clonality exist on the bottom of each endometrial gland and genetic alterations occurring in such cells may play a critical role in endometrial carcinogenesis. The possible association between area-specific X inactivation of the endometrial surface and the endometrial receptivity of embryo implantation remains to be clarified.     

Association between central sensitivity syndrome and psychological factors in people with presurgical low back pain: A cross-sectional study

BackgroundLow back pain (LBP) is a major problem; it causes significant burden, incurs considerable economic and human costs, and adversely affects the quality of life (QoL). Central sensitivity syndrome (CSS) is known as a group of overlapping conditions that share a common pathophysiological mechanism of central sensitization. Previous studies have shown that CSS is present in several disorders. However, it has been studied for people with presurgical LBP. The purpose of the study was to investigate the proportion of patients with CSS for presurgical LBP and to analyse the association of CSS with clinical symptoms and psychological factors.MethodsData of demographics, the central sensitization inventory (CSI), psychological measures, clinical symptoms of 238 patients with presurgical LBP were evaluated. The patients were divided into two groups depending on the CSI scores (≥40 and < 40). The two groups were compared, and the correlation between the CSI scores and other outcomes was analysed. Furthermore, multiple regression analysis was performed to identify factors contributing to the CSI scores.Results13.0% of participants were CSS. All outcomes were significantly different between the groups and significant associations were found between the CSI scores and all other outcomes. In addition, Pain Catastrophizing Scale (PCS) was most significant associated scale for the CSI scores.ConclusionWe found that certain patients had CSS with presurgical LBP. The CSI scores were significantly associated with the majority of the factors. The PCS was the factor with the most influence on the CSI scores.     

A Pilon Fracture With Fibular Head Dislocation Treated With the Use of 3D Preoperative Planning: A Case Report and Literature Review

Pilon fractures with intact fibula have been associated with low-energy trauma. However, the compression force onto the ankle joint can damage the tibiofibular linkage as in a Maisonneuve fracture. Herein, we describe a case of a patient who had a pilon fracture (AO type 43 C3.2) without a fibular fracture. Three-dimensional preoperative simulation by reduction with the surface registration technique was performed as the fibular length was intact and there was no reference for the tibial length. The preoperative simulation revealed superior fibular head dislocation and shortening of the distal tibia. After emergency external fixation on the day of arrival, a 2-staged surgery was performed. During the first operation, the fibular head was reduced and the tibial posterolateral fragment was fixed to restore the tibia length. During the second operation, medial and anterolateral fragments were fixed in order to reduce joint surface of the distal tibia. In general, proximal fibular head fractures are easily overlooked. In the case of pilon fractures with severe length shortening of the tibia without a fibular fracture, a proximal tibiofibular injury should be suspected.     

Tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2) stimulate osteoclastic bone resorption

As both tissue inhibitor of metalloproteinases-1 (TIMP-1) and TIMP-2 have been reported to inhibit bone resorption, we examined whether TIMP-1 or TIMP-2 in fetal calf serum (FCS), with which culture media were supplemented, affected osteoclastic bone resorption in vitro. Contrary to our expectation, almost complete suppression of osteoclastic bone resorption was observed when both TIMP-1 and TIMP-2 were removed from the FCS. Bone resorption was, however, almost fully restored by the addition of recombinant TIMPs. TIMPs stimulate bone resorption at significantly lower concentrations (∼ng/ml) than those (∼μg/ml) required to inhibit bone resorption. To understand the mechanism of TIMP-dependent bone resorption, we counted and compared the number of tartrate-resistant acid phosphatase-(TRAP-) positive and multinuclear cells in cultures containing either 10% FCS or TIMP-1-free and/or TIMP-2-free FCS. There was essentially no difference in number among these, suggesting that the TIMP role seems to be related to the functional expression of osteoclasts. Metallo-proteinase inhibitors, either BE16627B[l-N-(N-hydroxy-2-isobutylsuccinynamoyl)-seryl-l-valine] or R94138 {N-methyl-(3S)-2-[(2R)-2-hydroxycarbamoylmethylundecanoyl] hexahydropyridazine-3-carboxamide}, could not replace TIMPs, suggesting that the osteoclast-stimulating activity of TIMPs cannot be ascribed to merely their inhibitory effect on matrix metalloproteinases. Received: Oct. 15, 1998 / Accepted: April 5, 1999     

Programming a predictive rormula for angina and other risk factors in patients with cardiac diseases undergoing noncardiac operations

We programmed a formula which predicts the incidence of either myocardial infarction or cardiac death during the postoperative period. The original formula was proposed by Shah et al, based on their own data and analysis. The program is simple and is written in a language called Quick Basic. The use of this program is also simple. Such a program has improved the use of this analysis substantially. The program has been posted on to a few Computer network services as a free software.(Suwa K, Ogura S: Programming a predictive formula for angina and other risk factors in patients with cardiac diseases undergoing non-cardiac operations. J Anesth 6: 241–242, 1992)     

Clinical analysis of ossified thoracic ligaments and thoracic disc hernia]

Thoracic lesions present several clinical problems, particularly in their diagnosis and treatment, compared with cervical or lumbar lesions. Since 1983, 18 cases of thoracic space lesions, excluding spinal tumors or trauma have been experienced: nine cases of ossification of yellow ligament (OYL), five of ossification of posterior longitudinal ligament (OPLL), and four of disc hernia (DH). In these 18 patients, problems of clinical manifestations, neuroradiological examination, and surgical approaches are analyzed and discussed. As clinical manifestations, there was a preponderant occurrence in males in the OYL group, while in the OPLL group all the patients were females. OYL and DH occurred at lower thoracic levels. Thirteen of the 18 patients showed combined lesions either in the cervical or in the lumbar regions, such as cervical OPLL, cervical spondylosis, lumbar DH, and lumbar canal stenosis. In the neuroradiological examinations diagnosis of the upper thoracic lesions was difficult. Computed tomography (CT) scan with intrathecal metrizamide injection seemed essential for examination of ossified thoracic lesions. However, because CT imaging of the entire spine is impractical, efficient use of this examination requires previous localization of the offending vertebral level from either the neurological findings or other neuroradiological examinations such as myelography. Magnetic resonance imaging seemed most useful for ruling out the thoracic compressing lesions. As for surgical approaches, posterior decompression was effective for OYL and the anterior approach was useful for OPLL and DH. In patients with "tandem lesions," neurological and neuroradiological findings played an important role in deciding the responsible site.