Differential diagnosis between complete and partial hydatidiform mole is clinically important because of the difference in the risk of developing more malignant form of the molar diseases. In this report, the classical microscopic criteria were re-evaluated in the light of the immunohistochemistry of p57KIP2 in the attempt to establish robust morphological criteria for the differential diagnosis. Thirty-six consecutive cases clinically suspected to be hydatidiform mole were employed. The histological criteria were scored by three pathologists. The cases were categorized into three entities of the molar diseases in accordance with the immunohistochemistry of p57KIP2 and CD34. The diagnostic significance of the histological criteria was evaluated in a logistic regression model. Of 36 cases, the immunohistochemistry revealed that 28 were complete and 6 were partial hydatidiform mole, while 2 cases were hydropic abortion. A stepwise logistic regression analysis indicated that, among seven criteria studied, three of them (shape of villi, prevalence of villi with three types of trophoblasts, and predominance of villi with hydropic change) were useful to differentiate complete hydatidiform mole from partial one. This observation may be applicable in the pathological diagnosis of the molar diseases.
Short-chain fatty acids (SCFAs), including acetate, propionate and butyrate, are the most commonly found anions found in the monogastric mammalian large intestine, and are known to have a variety of physiological and pathophysiological effects on the gastrointestinal tract. We investigated the protein and mRNA expression levels of GPR41, a possible G protein coupled receptor for SCFA, using Western blot analysis and reverse transcriptase-polymerase chain reaction. We found that GPR41 protein and mRNA are expressed in human colonic mucosa. Immunohistochemistry for GPR41 showed that mucosal GPR41 protein is localized in cytoplasm of enterocytes and enteroendocrine cells. Moreover, GPR41-immunoreactive endocrine cells contained peptide YY but not serotonin or GPR43. The cellular population of GPR41 (0.01 ± 0.01 cells/crypt) was much smaller than that of GPR43 (0.33 ± 0.01 cells/crypt) in the human colon. However, the potency order of SCFA-induced phasic contraction of colonic smooth muscle that we previously reported is consistent with GPR41 (propionate >= butyrate > acetate) but not GPR43 (propionate = butyrate = acetate). Therefore, the present study suggests that GPR41 expressed in human colonic mucosa may function as a sensor for luminal SCFAs.
The effect of acute stress on the immune system was examined in mice. Restraint stress decreased the number of lymphocytes in the liver, whereas the number of lymphocytes remained unchanged in the spleen and thymus. In the liver, the decrease in number appeared at 1.5 h and fell to a third of he control level at 3 h. The proportions of IL-2Rβ+CD3int cells, NKT cells, CD44+ T cells and B cells were changed in the liver. The absolute numbers of IL-2Rβ+CD3int cells, NKT cells and CD3+CD44+ cells remained constant in the liver under the stress, while those of total T cells and NK cells decreased. The levels of hyaluronan (HA) in various tissues and sera were then examined. The expression of hyaluronan binding protein (HABP) was found to increase in the skin, liver and kidney as shown by immunohistochemical staining. An increase of HA in sera due to stress was seen at 3 h. The present results suggest that the activation of CD44+ T cells and unconventional T cells (i.e., innate immunity) in the blood and the elevated levels of HA (ligand for CD44) in the tissues and blood are crucial responses to acute stress exposure.
DNA fragmentation is a biochemical hallmark of apoptosis. Several endonucleases, including CAD/DFF40 and endonuclease G, are implicated in DNA fragmentation. DNase γ has also been considered to be one of the enzymes involved, but its role in relation to CAD/DFF40 in apoptosis has not been fully elucidated. Here, we distinguished between DNase γ-dependent and CAD/DFF40-dependent DNA fragmentations. We found that DNase γ activities appeared in the late apoptotic phase and accelerated DNA fragmentation. Thus, even if the apoptotic DNA fragmentation is initiated by CAD/DFF40, DNase γ is required for the more complete digestion of the genomic DNA in dying cells.
Signal transducer and activator of transcription (Stat) 3 and p53 integrate upstream signals, and are positive and negative regulators of tumor cell proliferation, respectively. Stat3 and p53 also negatively regulate each other. However, their roles remain elusive in patients with renal cell carcinoma (RCC). We quantified Stat3 and p53 mRNA expression in paired tumor and non-tumor surgical samples from 47 Japanese patients with RCC by the real-time reverse transcription polymerase chain reaction (RT-PCR) technique. Absolute levels of Stat3 and p53 mRNA were lower in tumor tissues compared with non-tumor tissues (P < 0.0001). The absolute levels of Stat3 and p53 mRNA in RCC tissue were not correlated with tumor histology, stage, or metastatic behavior. Kaplan-Meier analysis showed that a high level of Stat3 or p53 mRNA expression was associated with shorter overall survival compared to low expression (P = 0.254 and P = 0.066, respectively). In addition, the tumor tissue levels of Stat3 and p53 mRNA expression were correlated with each other (r2 = 0.697, P < 0.01). These findings suggest that Stat3 and p53 are cooperatively involved in the development of RCC, but assessment of their mRNA expression may not be useful for predicting the prognosis of patients with RCC.
Pulmonary fibrosis is a progressive and lethal lung disease characterized by accumulation of ECM and loss of pulmonary function. However, no cure exists for this disease, and current treatments often fail to slow its progression or relieve its symptoms. We have previously reported that the anti-fibrotic agent SMP-534 has beneficial effects on renal fibrosis in animal model of nephropathy. In this study, we examined whether SMP-534 has beneficial effects on pulmonary fibrosis in bleomycin-treated hamsters. Treatment with SMP-534 [low dose (70 mg/kg) or high dose (110 mg/kg)] counteracted inhibition of body weight increase induced by bleomycin. In addition, SMP-534 significantly inhibited bleomycin-induced increase in lung hydroxyproline level, an index of collagen formation. Moreover, SMP-534 significantly ameliorated histological pulmonary fibrotic changes induced by bleomycin. The results of this study indicate that the anti-fibrotic agent SMP-534 may offer a new therapeutic option for the treatment of pulmonary fibrosis.
The localization of the voltage-gated calcium channel (VGCC) α2 and the voltage-gated sodium channel (VGSC) α subunits was immunohistochemically investigated in chicken spinal motoneurons. Approximately 83% and 46% of spinal motoneurons were positive for VGCCα2 and VGSCα subunits, respectively. Almost all VGSCα subunit-positive motoneurons exhibited the VGCCα2 subunit immunoreactivity. There were different patterns in occurrence, intensity or nuclear/cytoplasmic stainability of the VGCCα2 and VGSCα subunits among the motoneurons. This study presents the first cellular morphological evidence for the VGCCα2 and VGSCα subunits in spinal motoneurons, postulating that the heterogeneous expression of VGCCα2 and VGSCα subunits in the motoneurons may reflect various motor activities.
Traditional titanium dioxide (TiO2) has photocatalytic bactericidal properties only under ultraviolet (UV) irradiation, which restricts its use in clinical treatment regimens. In this study, we evaluated the photocatalytic bactericidal effects of an aqueous system of TiO2 particles irradiated by fluorescent light (FL) on Staphylococcus aureus. A TiO2 particle mixture containing 19 ppm (0.019 mg/mL) of TiO2 was prepared. A bacterial solution of 1 × 105 CFU/mL was added one drop at a time to the TiO2 mixture. The resulting product was then irradiated with FL. The bacterial survival rate decreased steadily in the TiO2 mixture group, reaching 76.7% after 30 min of FL irradiation and 10.9% after 60 min. After 60 to 180 min, the bacterial survival ratio of the TiO2 mixture group was significantly lower than that of the control group (P < 0.05). The present study indicates that treating the surfaces of surgical devices and the surgical field with a TiO2 particle mixture can create a nearly sterile environment that can be maintained throughout surgery, even at low luminous intensities.
The epithelial Na+ channel (ENaC) contributes to control of blood pressure by reabsorbing Na+ in the cortical collecting duct of the kidney. The luminal Cl- concentration in the duct varies under physiological conditions. As the body Na+ content is lower, the luminal Cl- concentration in the duct becomes lower. Thus, we hypothesized that the extracellular Cl- elevates ENaC activity in AVT-stimulated renal epithelial A6 cells (a model cell line of the cortical collecting duct) leading to recovery from a low body Na+ content. To clarify this point, we studied effects of extracellular Cl- concentration on ENaC activity using cell-attached patch clamp technique. We found that ENaC had a single-channel conductance of 4.6 ± 0.1 pS (mean ± SE) and channel activity (open probability, Po) of 0.30 ± 0.02 at a pipette potential of 60 mV. Lowering pipette Cl- concentration diminished Po to 0.23 ± 0.02 associated with a significant decrease in open time from 0.78 ± 0.03 to 0.61 ± 0.02 s with no significant change in closed time, and shifted the current-voltage relationship leftward. These results suggest that the extracellular Cl- regulates the ENaC-mediated Na+ reabsorption by affecting ENaC properties in AVT-stimulated renal epithelial cells.