Temporal changes in the distribution and number of macrophage-lineage cells in the periodontal membrane of the rat molar in response to experimental tooth movement

In order to evaluate the possible role of macrophages in the remodelling of periodontal tissue in response to tooth movement, temporal changes in the number and distribution of macrophage-lineage cells in the periodontal membrane of the rat molar tooth after experimental tooth movement were examined immunohistochemically using four anti-rat monoclonal antibodies: ED1 (anti-monocyte/macrophage-lineage cells and dendritic cells), ED2 (anti-resident macrophages), KI-M2R (anti-tissue macrophages), and OX6 (anti-class II molecules). The right maxillary first molar tooth of Wistar rats was moved mesially by a closed-coil spring for 1, 3, 5, or 7 days. Sham-treated rats wearing an inactivated appliance for each experimental period and entirely untreated rats were used as controls. Alternate horizontal serial cryostat sections were cut and incubated with antibodies to ED1, ED2, KI-M2R, and OX6. In addition, cells immunopositive for each monoclonal antibody in the periodontal membrane during tooth movement were analysed on the tension and pressure sides. In the control rats, large numbers of cells positively stained with each monoclonal antibody were distributed throughout the periodontal membrane surrounding the distobuccal root. At 1 day after experimental tooth movement, the number of immunopositive cells obtained with all four monoclonal antibodies decreased as compared with those of the control on the mesial/pressure side. During the later experimental time periods, ED1- and OX6-positive cells in the periodontal membrane of this side were significantly increased in number compared with controls, whereas the density and distribution pattern of cells positive with ED2 or KI-M2R remained unchanged. On the mesial/pressure side, which underwent hyalinization, a marked accumulation of OX6- and ED1-reactive cells, but not of ED2- or KI-M2R-reactive cells, was frequently observed in the area of the hyalinized tissue at 5-7 days after the start of tooth movement. On the distal/tension side, no particular change in the distribution of immunopositive cells obtained with any antibody was detected throughout the experimental periods, with the exception that there was a significant increase in the number of ED1-positive cells and in of OX6-positive cells at 1 and 7 days, respectively, after the start of tooth movement. These results suggest that after the start of tooth movement OX6- and ED1-positive cells, which are mostly exudative macrophages, but not ED2- and KI-M2R-positive cells, i.e., resident macrophages, may be actively engaged in bone resorption and the remodelling of tissues on the pressure side of the periodontal membrane.     

Detection of Alzheimer’s disease-related neuroinflammation by a PET ligand selective for glial versus vascular translocator protein

A substantial and constitutive expression of translocator protein (TSPO) in cerebral blood vessels hampers the sensitive detection of neuroinflammation characterized by greatly induced TSPO expression in activated glia. Here, we conducted in vivo positron emission tomography (PET) and in vitro autoradiographic imaging of normal and TSPO-deficient mouse brains to compare the binding properties of ¹⁸F-FEBMP, a relatively novel TSPO radioligand developed for human studies based on its insensitivity to a common polymorphism, with ¹¹C-PK11195, as well as other commonly used TSPO radioligands including ¹¹C-PBR28, ¹¹C-Ac5216 and ¹⁸F-FEDAA1106. TSPO in cerebral vessels of normal mice was found to provide a major binding site for ¹¹C-PK11195, ¹¹C-PBR28 and ¹⁸F-FEDAA1106, in contrast to no overt specific binding of ¹⁸F-FEBMP and ¹¹C-Ac5216 to this vascular component. In addition, ¹⁸F-FEBMP yielded PET images of microglial TSPO with a higher contrast than ¹¹C-PK11195 in a tau transgenic mouse modeling Alzheimer’s disease (AD) and allied neurodegenerative tauopathies. Moreover, TSPO expression examined by immunoblotting was significantly increased in AD brains compared with healthy controls, and was well correlated with the autoradiographic binding of ¹⁸F-FEBMP but not ¹¹C-PK11195. Our findings support the potential advantage of comparatively glial TSPO-selective radioligands such as ¹⁸F-FEBMP for PET imaging of inflammatory glial cells.     

Postoperative Evaluation of Pylorus-Preserving Procedures Compared with Conventional Distal Gastrectomy for Early Gastric Cancer

We evaluated postoperative function in 98 patients who underwent surgery for early gastric cancer between 1995 and 1998 to compare the results of pylorus-preserving procedures to those of conventional distal gastrectomy with Billroth I (B-I). The pylorus-preserving procedures included endoscopic mucosal resection (EMR), performed in 12 patients; local resection (Local), performed in 14 patients; segmental resection (Seg), performed in 8 patients; and pylorus-preserving gastrectomy (PPG), performed in 19 patients. B-I was performed in 45 patients. The nutritional status and serum albumin (Alb) levels after PPG, the hemoglobin (Hb) levels after EMR, Local, and PPG, and the present/preoperative body weight ratios after EMR, Local, Seg, and PPG were superior to those after B-I. The time before oral intake was recommenced after EMR and Local, the volume of oral intake tolerated after EMR, Local, Seg, and PPG, and the postoperative hospital stay after EMR were all superior to those after B-I. Moreover, significantly fewer patients suffered reflux symptoms after EMR, Local, and PPG, abdominal fullness after EMR, and early dumping syndrome after EMR, Local, and PPG than after B-I. There was also less evidence of gastritis after EMR, Local, and PPG, and of bile reflux after EMR, Local, and PPG, than after B-I. These findings indicate that pylorus-preserving procedures may result in a better postoperative quality of life for selected patients with early gastric cancer. Received: September 28, 2000 / Accepted: March 6, 2001     

Changes in Portal Systemic Pressure Gradient After Balloon-Occluded Retrograde Transvenous Obliteration of Gastric Varices and Aggravation of Esophageal Varices

The purpose of this study was to evaluate change in the portal systemic pressure gradient (PSPG) following balloon-occluded retrograde transvenous obliteration (BRTO) and the aggravation of esophageal varices. The PSPG was monitored before and after BRTO in 19 patients. PSPG changes were obtained by subtracting the PSPG before BRTO from that after BRTO. The development of outflow vessels (e.g., left inferior phrenic vein) was classified into two grades: Grade 1, BRTO alone; and Grade 2, coil embolization plus BRTO. After confirming demonstration of the whole gastric varices on angiography and computed tomography, BRTO was conducted using a 5% ethanolamine-iopamidol mixture. Endoscopy was performed to evaluate gastric and esophageal varices before, within 1 month, and 3–6 months after BRTO. Eradication of gastric varices was obtained in all patients and aggravation of esophageal varices was seen in 11 patients. The PSPG was significantly elevated by BRTO (p = 0.0362). The PSPG was significantly elevated in patients with Grade 2 compared with those with Grade 1 (7.7 ± 3.7 vs. 3.3 ± 4.3 mmHg, respectively; p = 0.0314) and in those with esophageal varices before treatment compared with those without (7.4 ± 4.0 vs. 3.2 ± 3.9 mmHg, respectively; p = 0.0482). The cumulative aggravation rate of esophageal varices was significantly higher in 11 patients with a PSPG elevation >5 mmHg than in 8 patients with one of ≤5 mmHg (p = 0.0105). In conclusion, BRTO induced a significant elevation in PSPG, with the degree of elevation influencing the aggravation of esophageal varices following BRTO.     

Downregulation of Tie2 gene by a novel antitumor sulfolipid, 3'-sulfoquinovosyl-1'-monoacylglycerol, targeting angiogenesis

We previously reported that 3'-sulfoquinovosyl-1'-monoacylglycerol (SQMG) was effective in suppressing the growth of solid tumors due to hemorrhagic necrosis in vivo . In the present study, we investigated the antiangiogenic effect of SQMG. In vivo assessment of antitumor assays showed that some tumor cell lines, but not others, were sensitive to SQMG. Microscopic study suggested that in SQMG-sensitive tumors, but not SQMG-resistant tumors, angiogenesis was reduced. We next investigated gene expression relating to angiogenesis in tumor tissues by quantitative real-time polymerase chain reaction. Consequently, although vascular endothelial growth factor gene expression was not detected with significant differences among the cases, significant downregulation of Tie2 gene expression was observed in all SQMG-sensitive tumors as compared with controls, but not in SQMG-resistant tumors. These data suggested that the antitumor effects of SQMG could be attributed to antiangiogenic effects, possibly via the downregulation of Tie2 gene expression in SQMG-sensitive tumors. ( Cancer Sci 2008; 99: 1063–1070)     

Natural Antigenic Peptides from Squamous Cell Carcinoma Recognized by Autologous HLA-DR8–restricted CD4+ T Cells

A large number of human tumor antigens recognized by CD8⁺ cytotoxic T lymphocytes (CTL) have been identified. Some of them have been employed in clinical trials and have achieved some objective responses. However, little is known about those that are recognized by CD4⁺ T cells, except for a very few that were identified from melanomas. Previously, we reported that an oral squamous cell carcinoma (SCC) cell line, OSC–20, was effectively lysed by HLA-DRB1·08032 (HLA-DRS)-restricted autologous CD4⁺ T cell line, TcOSC–20. In this study, we performed two steps of chromatographic purification of the tumor cell lysate in combination with mass spectrometry. We found one reverse-phase high-performance liquid chromatography (RP-HPLC) fraction that was effectively recognized by the T cells. We analyzed the fraction by nano-liquid chromatography/electrospray ionization ion trap mass spectrometry (LC/MS/MS) and found six representative ions. We could determine the primary amino acid sequence of each of the six ions. Three of them contained a potential HLA-DR8 binding motif, and TcOSC–20 showed a rather strong cytotoxic response to one of the synthetic pep tides, namely, amino acid residues 321–336 of human a-enolase. Thus, several gene products of squamous cancer cells are endogenously processed and may be presented on HLA class II molecules, so that they could constitute target molecules for autologous CD4⁺ T cells.     

Immediate hypersensitivity reactions to iodinated contrast media: The diagnosis of allergy by skin testing

Among 74 patients with an immediate hypersensitivity reaction (IHR) to iodinated contrast media (ICM), the rate of allergic patients confirmed by positive prick test or diluted intradermal test (IDT) was 8.1%. 12.5% of re‐exposed patients had a recurrent IHR despite negative skin tests. Investigations on pure IDT to ICM and development of drug provocation test may provide additional safety nets to uncover recurrent ICM reactors. Agreements among allergists are needed to unify practices.     

Evolution of a Systematic Approach to Smoking Cessation in Ontario’s Regional Cancer Centres

Smoking cessation after a cancer diagnosis can significantly improve a person’s prognosis, treatment efficacy and safety, and quality of life. In 2012, Cancer Care Ontario (now part of Ontario Health) introduced a Framework for Smoking Cessation, to be implemented for new ambulatory cancer patients at the province’s 14 Regional Cancer Centres (RCCs). Over time, the program has evolved to become more efficient, use data for robust performance management, and broaden its focus to include new patient populations and additional data collection. In 2017, the framework was revised from a 5As to a 3As brief intervention model, along with an opt-out approach to referrals. The revised model was based on emerging evidence, feedback from stakeholders, and an interim program evaluation. Results showed an initial increase in referrals to cessation services. Two indicators (tobacco use screening and acceptance of a referral) are routinely monitored as part of Ontario Health’s system-wide performance management approach, which has been identified as a key driver of change among RCCs. Due to the COVID-19 pandemic, many RCCs reported a decrease in these indicators. RCCs that were able to maintain a high level of smoking cessation activities during the pandemic offer valuable lessons, including the opportunity to swiftly leverage virtual care. Future directions for the program include capturing data on cessation outcomes and expanding the intervention to new populations. A focus on system recovery from COVID-19 will be paramount. Smoking cessation must remain a core element of high-quality cancer care, so that patients achieve the best possible health benefits from their treatments.     

Deterioration of baroreflex by transient global cerebral ischemia: its correlation with the degree of ischemia or post-ischemic hypoperfusion in the medulla oblongata

In a canine model of transient global cerebral ischemia, the correlation between the decrease in baroreflex sensitivity (BRS) following 5-min ischemia and the degree of ischemia or post-ischemic hypoperfusion was investigated. Although the medulla oblongata and the cerebral cortex suffered a similar degree of ischemia, the extent of post-ischemic decrease in BRS was inversely correlated with the residual blood flow during ischemia in the medulla, but not with that in the cerebral cortex. A similar degree of post-ischemic hypoperfusion occurred in the medulla and the cerebral cortex. However, the extent of decrease in BRS was not correlated with the degree of hypoperfusion, and the cortical EEG was not significantly affected. These results suggest that the decrease in BRS may be due to the functional damage in the medulla and that the selective decrease in BRS without concomitant impairment of the EEG cannot be ascribed to the regional difference in the degree of ischemia or post-ischemic hypoperfusion.