Mitochondrial complex II in intestinal epithelial cells regulates T cell-mediated immunopathology.

Intestinal epithelial cell (IEC) damage by T cells contributes to graft-versus-host disease, inflammatory bowel disease and immune checkpoint blockade-mediated colitis. But little is known about the target cell-intrinsic features that affect disease severity. Here we identified disruption of oxidative phosphorylation and an increase in succinate levels in the IECs from several distinct in vivo models of T cell-mediated colitis. Metabolic flux studies, complemented by imaging and protein analyses, identified disruption of IEC-intrinsic succinate dehydrogenase A (SDHA), a component of mitochondrial complex II, in causing these metabolic alterations. The relevance of IEC-intrinsic SDHA in mediating disease severity was confirmed by complementary chemical and genetic experimental approaches and validated in human clinical samples. These data identify a critical role for the alteration of the IEC-specific mitochondrial complex II component SDHA in the regulation of the severity of T cell-mediated intestinal diseases.

Impacts of probiotics on the efficacies of immune checkpoint inhibitors with or without chemotherapy for patients with advanced non-small-cell lung cancer.

The relationships between the therapeutic effects of immune checkpoint inhibitors (ICIs) and the intestinal flora have attracted increasing attention. However, the effects of oral probiotics on the efficacies of ICIs used to treat non-small-cell lung cancer (NSCLC) remain unclear. We investigated the effects of probiotics on the efficacies of ICIs in patients treated with and without chemotherapy. We investigated patients with advanced NSCLC on ICI monotherapy or combination ICI and chemotherapy using the Okayama Lung Cancer Study Group Immunotherapy Database (OLCSG-ID) and the Okayama Lung Cancer Study Group Immunochemotherapy Database (OLCSG-ICD). In total, 927 patients (482 on ICI monotherapy, 445 on an ICI + chemotherapy) were enrolled. Most were male, of good performance status, smokers, and without epidermal growth factor receptor (EGFR)/anaplastic lymphoma kinase (ALK) mutations. Probiotics were administered to 19% of patients on ICI monotherapies and 17% of those on ICIs + chemotherapy. Of the former patients, progression-free survival (PFS) and overall survival (OS) were significantly better in the probiotics group (PFS 7.9 vs. 2.9 months, hazard ratio [HR] 0.54, p < .001; OS not attained vs. 13.1 months, HR 0.45, p < .001). Among patients receiving ICI and chemotherapy, there were no significant differences in PFS between those on probiotics and not but OS was significantly better in the probiotics group (PFS 8.8 vs. 8.6 months, HR 0.89, p = .43; OS not attained vs. 22.6 months, HR 0.61, p = .03). Patients on probiotics experienced better outcomes following ICI treatment.

Antitumor activity of α-pinene in T-cell tumors.

T-cell acute leukemia and lymphoma have a poor prognosis. Although new therapeutic agents have been developed, their therapeutic effects are suboptimal. α-Pinene, a monoterpene compound, has an antitumor effect on solid tumors; however, few comprehensive investigations have been conducted on its impact on hematologic malignancies. This report provides a comprehensive analysis of the potential benefits of using α-pinene as an antitumor agent for the treatment of T-cell tumors. We found that α-pinene inhibited the proliferation of hematologic malignancies, especially in T-cell tumor cell lines EL-4 and Molt-4, induced mitochondrial dysfunction and reactive oxygen species accumulation, and inhibited NF-κB p65 translocation into the nucleus, leading to robust apoptosis in EL-4 cells. Collectively, these findings suggest that α-pinene has potential as a therapeutic agent for T-cell malignancies, and further investigation is warranted.

Collection efficiency and safety of large-volume leukapheresis for the manufacturing of tisagenlecleucel.

BACKGROUND: In patients with relapsed or refractory B cell acute lymphoblastic leukemia or B cell non-Hodgkin lymphoma (r/r B-ALL/B-NHL) with low CD3+ cells in the peripheral blood (PB), sufficient CD3+ cell yield in a single day may not be obtained with normal-volume leukapheresis (NVL). Large-volume leukapheresis (LVL) refers to the processing of more than three times the total blood volume (TBV) in a single session for PB apheresis; however, the efficiency and safety of LVL for manufacturing of tisagenlecleucel (tisa-cel) remain unclear. This study aimed to investigate the tolerability of LVL. STUDY DESIGN AND METHODS: We retrospectively collected data on LVL (≥3-fold TBV) and NVL (<3-fold TBV) performed for patients with r/r B-ALL/B-NHL in our institution during November 2019 and September 2023. All procedures were performed using a continuous mononuclear cell collection (cMNC) protocol with the Spectra Optia. RESULTS: Although pre-apheresis CD3+ cells in the PB were significantly lower in LVL procedures (900 vs. 348/µL, p < .01), all patients could obtain sufficient CD3+ cell yield in a single day with a comparably successful rate of final products (including out-of-specification) between the two groups (97.2% vs. 100.0%, p = 1.00). The incidence and severity of citrate toxicity (no patients with grade ≥ 3) during procedures was not significantly different between the two groups (22.2% vs. 26.1%, p = .43) and no patient discontinued leukapheresis due to any complications. CONCLUSION: LVL procedures using Spectra Optia cMNC protocol was well tolerated and did not affect the manufacturing of tisa-cel.

An open-label study of belumosudil, a selective ROCK2 inhibitor, as second or subsequent line of therapy for steroid-dependent/steroid-resistant chronic GVHD.

Belumosudil mesylate is a selective Rho-associated coiled-coil kinase 2 inhibitor with immunomodulatory and antifibrosis effects. This multicenter, open-label, single-arm study evaluated belumosudil 200 mg once daily as second or subsequent line of therapy (LOT) in 21 Japanese patients ≥12 years of age with steroid-dependent/steroid-resistant chronic graft-versus-host disease (cGVHD). The primary endpoint of best overall response rate (ORR) at 24 weeks after enrollment of the last patient was 85.7% (95% confidence interval [CI]: 63.7-97.0), and the lower limit of the 95% CI exceeded the pre-defined threshold of 25%. The Kaplan-Meier estimate of duration of response rate at 24 weeks was 75% (95% CI: 46-90); 13/18 responders (72.2%) had a sustained response for ≥20 weeks. The median time to response was 4.1 weeks (range 3.90-8.10); ORR was 47.6% at 4 weeks and 75.0% at 24 weeks; best ORR was 80% for joints/fascia, 66.7% for the mouth, and 54.5% for skin. Overall, 57.1% of patients had clinically meaningful symptom improvement at least once; the median duration of symptom improvement was 22.2 weeks (range 4.0-51.3). Corticosteroid dose reductions were recorded for 57.1% of patients. Median failure-free and overall survival were not reached. Treatment-emergent adverse events occurred in 85.7% of patients (most commonly diarrhea, 19.0%), of which 38.1% were drug-related. There were no drug-related discontinuations or deaths. In summary, belumosudil 200 mg once daily as second or subsequent LOT in Japanese patients with steroid-dependent/steroid-resistant cGVHD was effective, with no new safety concerns.

A review of the directly sampled endometrial cytology on LBC samples: Classification, microscopic criteria and beyond.

The Yokohama System for Reporting Endometrial Cytology (TYS) has been proposed by an expert meeting under the auspices of the International Academy of Cytology (IAC) in May 2016 at the IAC in Yokohama. Since its introduction, the TYS has been receiving worldwide acceptance, and this review aims to assess its global impact. The adoption of endometrial cytology as a diagnostic procedure has been hampered in the past by difficulties arising in interpreting the cellular findings due to a number of factors (such as excess blood, cellular overlapping and the complex physiology of endometrium). Recently, the use of liquid-based cytology (LBC), with its ability to remove blood and mucus and to distribute cells uniformly in a thin layer on the slide, has provided an opportunity to re-evaluate the role of endometrial cytology. LBC is a useful tool in the cytologic diagnosis and follow-up of endometrial abnormalities, which remains complementary to the emerging molecular diagnostic cytopathology. The study of LBC from endometrial cytology could be challenging since it is affected by numerous look-alikes and diagnostic pitfalls. This review discusses these various entities and takes into consideration the ancillary techniques that may be useful in the diagnostic procedure. In conclusion, our review of the published data suggests that the TYS is a valid classification scheme that has been widely accepted by cytopathologists globally, is highly reproducible and makes a valuable contribution to clinical therapeutic management. At present, molecular cytopathology is a rapidly evolving field of modern cytopathology, which underlines the effective interplay between genomics and cytology. This review aims to provide a comprehensive review of the drawbacks of endometrial cytopathology, particularly in terms of endometrial cancer diagnosis and molecular testing.

The Roles of Neuropeptide Y in Respiratory Disease Pathogenesis via the Airway Immune Response.

The lungs are very complex organs, and the respiratory system performs the dual roles of repairing tissue while protecting against infection from various environmental stimuli. Persistent external irritation disrupts the immune responses of tissues and cells in the respiratory system, ultimately leading to respiratory disease. Neuropeptide Y (NPY) is a 36-amino-acid polypeptide and a neurotransmitter that regulates homeostasis. The NPY receptor is a seven-transmembrane-domain G-protein-coupled receptor with six subtypes (Y1, Y2, Y3, Y4, Y5, and Y6). Of these receptors, Y1, Y2, Y4, and Y5 are functional in humans, and Y1 plays important roles in the immune responses of many organs, including the respiratory system. NPY and the Y1 receptor have critical roles in the pathogenesis of asthma, chronic obstructive pulmonary disease, and idiopathic pulmonary fibrosis. The effects of NPY on the airway immune response and pathogenesis differ among respiratory diseases. This review focuses on the involvement of NPY in the airway immune response and pathogenesis of various respiratory diseases.

Sigle Agent of Posttransplant Cyclophosphamide Without Calcineurin Inhibitor Controls Severity of Experimental Chronic GVHD.

Chronic graft-versus-host disease (GVHD) is a major cause of late death and morbidity following allogeneic hematopoietic cell transplantation (HCT), but its pathogenesis remains unclear. Recently, haplo-identical HCT with post-transplant cyclophosphamide (Haplo-HCT with PTCY) was found to achieve a low incidence rate of acute GVHD and chronic GVHD. However, while the pathogenesis of acute GVHD following Haplo-HCT with PTCY has been well investigated, that of chronic GVHD remains to be elucidated, especially in HLA-matched HCT with PTCY. Based on its safety profile, PTCY is currently applied for the human leucocyte antigen (HLA)-matched HCT setting. Here, we investigated the mechanisms of chronic GVHD following HLA-matched HCT with PTCY using a well-defined mouse chronic GVHD model. PTCY attenuated clinical and pathological chronic GVHD by suppressing effector T-cells and preserving regulatory T-cells compared with a control group. Additionally, we demonstrated that cyclosporine A (CsA) did not show any additional positive effects on attenuation of GVHD in PTCY-treated recipients. These results suggest that monotherapy with PTCY without CsA could be a promising strategy for the prevention of chronic GVHD following HLA-matched HCT.

[A case of small intestinal endometriosis with bowel obstruction and perforation].

A 47-year-old woman was referred to our hospital with recurring lower abdominal pain persisting for more than 2 weeks. Imaging modalities showed small bowel obstruction caused by a mass lesion in the terminal ileum. Despite undergoing fasting, rehydration, and decompression through an ileus tube, her symptoms persisted. Furthermore, the condition deteriorated on day 4, with the onset of her menstrual period. An emergency surgery was conducted on the 7th day after hospitalization. Surgical observations indicated severe stenosis around the ileocecal valve and ileal perforation approximately 40cm from the oral stricture. As a result, ileocecal resection was performed. Pathological examination revealed endometrial tissue infiltration through the mucosal lamina propria to the ileal subserosa. Thus, the patient was identified with intestinal endometriosis of the ileocecum. Endometriosis of the small bowel is an uncommon condition that eventually causes intractable bowel obstruction. Although preoperative diagnosis is considered challenging, intestinal endometriosis should be included in the differential diagnosis in cases of bowel obstruction in women of childbearing age.

The mechanism for regulating the isometric contraction of masseter muscles is involved in determining the vertical dimension of occlusion.

We previously demonstrated that accurate regulation of isometric contraction (IC) of jaw-closing muscles to counteract the ramp load applied to the jaw in the jaw-opening direction is achieved through the calibration between the two sensations arising from muscle spindles (MSs) and periodontal mechanoreceptors (PMRs). However, it remains unclear whether this calibration mechanism accurately works at any jaw positions, i.e., any vertical dimensions of occlusion (VDO). In the present study, we examined the effects of altering VDO on the IC of the masseter muscles in complete dentulous and edentulous subjects. At a VDO higher than the original VDO (O-VDO), the root mean square (RMS) of masseter EMG activity increased more steeply with a load increase, resulting in an over-counteraction. The regression coefficient of the load-RMS relationship significantly increased as the VDO was increased, suggesting that the overestimation became more pronounced with the VDO increases. Consistently also in the edentulous subjects, at a higher VDO than the O-VDO, a steeper increase in the RMS emerged with a delay in response to the same ramp load whereas a similar steeper increase was seen surprisingly even at a lower VDO. Thus, the edentulous subjects displayed a delayed overestimation of the ramp load presumably due to less and slowly sensitive mucous membrane mechanoreceptor (MMR) in alveolar ridge compared with the PMR. Taken together, the accurate calibration between the two sensations arising from MSs and PMRs/MMRs can be done only at the O-VDO, suggesting that the O-VDO is the best calibration point for performing accurate IC.NEW & NOTEWORTHY Since 1934, the vertical dimension of occlusion (VDO) in edentulous individuals has been anatomically determined mostly by referring to the resting jaw position. However, such a static method is not always accurate. Considering the dynamic nature of clenching/mastication, it is desirable to determine VDO dynamically. We demonstrate that VDO can be accurately determined by measuring masseter EMG during the voluntary isometric contraction of jaw-closing muscles exerted against the ramp load in the jaw-opening direction.

Trends in non-Hodgkin lymphoma mortality rate in Japan and the United States: A population-based study.

Characterizing trends in mortality rates with consideration of trends in incidence rates at the population level could help identify unmet needs in public health and provide essential indicators of cancer control. In the late 20th century, the arrival of the first molecular targeted agent, rituximab, for non-Hodgkin lymphoma (NHL) led to a paradigm shift in NHL treatment. However, the public health impact of this arrival has not been fully clarified. Here, we evaluated trends in the mortality and incidence rates of NHL in Japan and the United States. Age-standardized rates of mortality reversed after the introduction of rituximab, around 2000, beginning to decline significantly with annual percent changes (95% confidence interval) of -2.6% (-3.6% to -1.6%) in Japan and - 3.9% (-4.2% to -3.5%) in the United States. Despite an increase in incidence, the mortality in all age groups weakened the upward trends or decreased in both countries. From a long-term perspective, the trends in mortality rates differed between the countries. In the United States, the mortality rate has declined continuously since the introduction of rituximab, with a declining incidence rate. In contrast, in Japan, the mortality rate stopped declining and the incidence rate increased remarkably. The introduction of rituximab has had a substantial impact at the population level across a wide range of individuals. To reduce the disease burden in terms of mortality, elucidating risk factors that lead to a decreasing incidence rate is warranted for NHL, as well as further development of novel treatments.

Efficacy of gilteritinib in comparison with alectinib for the treatment of ALK-rearranged non-small cell lung cancer.

Gilteritinib is a multitarget tyrosine kinase inhibitor (TKI), approved for the treatment of FLT3-mutant acute myeloid leukemia, with a broad range of activity against several tyrosine kinases including anaplastic lymphoma kinase (ALK). This study investigated the efficacy of gilteritinib against ALK-rearranged non-small cell lung cancers (NSCLC). To this end, we assessed the effects of gilteritinib on cell proliferation, apoptosis, and acquired resistance responses in several ALK-rearranged NSCLC cell lines and mouse xenograft tumor models and compared its efficacy to alectinib, a standard ALK inhibitor. Gilteritinib was significantly more potent than alectinib, as it inhibited cell proliferation at a lower dose, with complete attenuation of growth observed in several ALK-rearranged NSCLC cell lines and no development of drug tolerance. Immunoblotting showed that gilteritinib strongly suppressed phosphorylated ALK and its downstream effectors, as well as mesenchymal-epithelial transition factor (MET) signaling. By comparison, MET signaling was enhanced in alectinib-treated cells. Furthermore, gilteritinib was found to more effectively abolish growth of ALK-rearranged NSCLC xenograft tumors, many of which completely receded. Interleukin-15 (IL-15) mRNA levels were elevated in gilteritinib-treated cells, together with a concomitant increase in the infiltration of tumors by natural killer (NK) cells, as assessed by immunohistochemistry. This suggests that IL-15 production along with NK cell infiltration may constitute components of the gilteritinib-mediated antitumor responses in ALK-rearranged NSCLCs. In conclusion, gilteritinib demonstrated significantly improved antitumor efficacy compared with alectinib against ALK-rearranged NSCLC cells, which can warrant its candidacy for use in anticancer regimens, after further examination in clinical trial settings.

Bone marrow microenvironment disruption and sustained inflammation with prolonged haematologic toxicity after CAR T-cell therapy.

Mechanisms of prolonged cytopenia (PC) after chimeric antigen receptor (CAR) T-cell therapy, an emerging therapy for relapsed or refractory diffuse large B-cell lymphoma, remain elusive. Haematopoiesis is tightly regulated by the bone marrow (BM) microenvironment, called the 'niche'. To investigate whether alterations in the BM niche cells are associated with PC, we analysed CD271+ stromal cells in BM biopsy specimens and the cytokine profiles of the BM and serum obtained before and on day 28 after CAR T-cell infusion. Imaging analyses of the BM biopsy specimens revealed that CD271+ niche cells were severely impaired after CAR T-cell infusion in patients with PC. Cytokine analyses after CAR T-cell infusion showed that CXC chemokine ligand 12 and stem cell factor, niche factors essential for haematopoietic recovery, were significantly decreased in the BM of patients with PC, suggesting reduced niche cell function. The levels of inflammation-related cytokines on day 28 after CAR T-cell infusion were consistently high in the BM of patients with PC. Thus, we demonstrate for the first time that BM niche disruption and sustained elevation of inflammation-related cytokines in the BM following CAR T-cell infusion are associated with subsequent PC.

Characteristic differences in the abundance of tumor-infiltrating lymphocytes and intratumoral developing T cells in thymoma, with special reference to PD-1 expression.

PURPOSE: Though programmed cell death-1 (PD-1) inhibitors mainly target tumor-infiltrating lymphocytes (TILs) expressing PD-1, developing T cells in thymus also express PD-1 in their process of maturation. To predict the therapeutic effect of PD-1 inhibitors for thymoma, it is necessary to clarify the proportions of TILs and intratumoral developing T cells. METHODS: The expressions of CD4, CD8, and PD-1 on T cells were analyzed by flow cytometry in 31 thymomas. The amount of T cell receptor excision circles (TRECs), which can be detected in newly formed naïve T cells in the thymus, was evaluated using sorted lymphocytes from thymomas by quantitative PCR. The expressions of granzyme B (GZMB) and lymphocyte activation gene-3 (LAG-3) in PD-1 + CD8 T cells were analyzed by image cytometry using multiplex immunohistochemistry. RESULTS: The PD-1 + rate in both CD4 and CD8 T cells was significantly higher in type AB/B1/B2 than in type A/B3 thymomas. The amounts of TRECs in CD4 and CD8 T cells were significantly higher in type AB/B1/B2 than in type A/B3 thymomas and comparable to normal thymus. PD-1 expression at each stage of T cell development of type AB/B1/B2 thymomas was comparable to that of normal thymus. Both the percentages and cell densities of PD-1 + CD8 T cells expressing GZMB or LAG-3, which are known to contain tumor-reactive T cells, were significantly lower in type AB/B1/B2 thymomas. CONCLUSION: Most PD-1 + T cells in type AB/B1/B2 thymomas are intratumoral developing T cells and are not TILs.

Effectiveness of cardiac palliative surgery for trisomy 18 patients with increased pulmonary blood flow.

Congenital heart disease (CHD) is common among patients with trisomy 18 (T18), but cardiac surgery has been rarely indicated for T18 patients due to their short life span. Although the therapeutic effects of aggressive interventions were recently demonstrated for T18 patients, the subjects and factors examined varied, resulting in inconsistent findings. Therefore, the effects of cardiac surgery for T18 remain unclear. We herein investigated the outcomes of cardiac palliative surgery for CHD with increased pulmonary blood flow in T18 patients. 27 patients were examined: 13 (48.1%) underwent cardiac palliative surgery and 14 (51.9%) did not. Median survival times in the no-surgery and surgery groups were 223.0 days (95% confidence interval [CI]: 46-361 days) and 723.0 days (95% CI: 360-1447 days), respectively. The number of patients with pulmonary hypertension significantly differed between the two groups (5 of 14 in the no-surgery group and 0 in the surgery group). Five of 14 patients in the no-surgery group and 10 of 13 in the surgery group were discharged to home care (odds ratio: 10.8 [95% CI: 1.07-110.0]). Therefore, cardiac palliative surgery may be used to treat CHD with increased pulmonary blood flow in T18 patients.

Evaluating the efficiency and safety of large-volume leukapheresis using the Spectra Optia continuous mononuclear cell collection protocol for peripheral blood stem cell collection from healthy donors: A retrospective study.

BACKGROUND: Large-volume leukapheresis (LVL) refers to processing of more than three volumes of blood in a single session for peripheral blood stem cell collection. Recently, continuous mononuclear cell collection (cMNC) protocol has been developed using the Spectra Optia system, which is a widely used apheresis device. LVL using the novel protocol has been investigated in patients. However, the efficiency and safety of LVL in healthy donors using this protocol has not been characterized. Therefore, this study aimed to evaluate the efficiency and tolerability of CD34+ collection of LVL with the cMNC protocol in healthy donors. STUDY DESIGN AND METHODS: We retrospectively collected data on LVL (>3 total blood volume) and normal-volume leukapheresis (NVL) performed in healthy donors between October 2019 and December 2021. All procedures were performed using the cMNC protocol. RESULTS: Although pre-apheresis CD34+ cell count was lesser in LVL (23.5 vs. 58.0/µL, p < .001), CD34+ collection efficiency was comparable between LVL and NVL (61.2% vs. 61.4%, p = .966). Platelet loss was significantly higher in LVL compared to NVL (38.0% vs. 29.4%, p < .001), with no correlation between attrition of platelet and processing blood volume. Moreover, the incidence of citrate toxicity during procedures was comparable between the two groups (31.6% vs. 21.4%, p = .322). All LVL procedures could be completed without any adverse events. CONCLUSION: Allogeneic LVL procedure using Spectra Optia cMNC protocol was well tolerated by the donors and resulted in efficient collection of CD34+ cells, which was comparable to that of NVL.

Efficient granulocyte collection method using high concentrations of medium molecular weight hydroxyethyl starch.

BACKGROUND: Granulocyte transfusion therapy is a rational therapeutic option for patients with prolonged, severe neutropenia. Although high molecular weight hydroxyethyl starch (hHES) facilitates the separation of red blood cells during granulocyte collection, renal dysfunction has been noted as a potential side effect. HES130/0.4 (Voluven®) is a medium molecular weight HES (mHES) with superior safety profiles compared to hHES. Although HES130/0.4 is reportedly effective in the collection of granulocytes, we lack studies comparing the efficiency of granulocyte collection using HES130/0.4 and hHES. STUDY DESIGN AND METHODS: We retrospectively collected the data from 60 consecutive apheresis procedures performed on 40 healthy donors at the Okayama University Hospital between July 2013 and December 2021. All procedures were performed using the Spectra Optia system. Based on the HES130/0.4 concentration in the separation chamber, granulocyte collection methods using HES130/0.4 were classified into m0.46, m0.44, m0.37, and m0.8 groups. We used HES130/0.4 and hHES groups to compare the various sample collection methods. RESULTS: The median granulocyte collection efficiency (CE) was approximately 24.0% and 28.1% in the m0.8 and hHES groups, respectively, which were significantly higher than those in the m0.46, m0.44, and m0.37 groups. One month following granulocyte collection with HES130/0.4, no significant changes were observed in serum creatinine levels compared to those before the donation. CONCLUSION: Therefore, we propose a granulocyte collection approach employing HES130/0.4, which is comparable to the use of hHES in terms of the granulocyte CE. A high concentration of HES130/0.4 in the separation chamber was considered crucial for granulocyte collection.

Relationship between carotid intima-media thickness and periodontal disease in a Japanese urban population with and without hypertension: The Suita Study.

AIM: To investigate the association between periodontal disease and atherosclerosis and to examine whether the association is modified by hypertension status. MATERIALS AND METHODS: In this cross-sectional study, 1472 Japanese individuals aged 50-79 years who underwent a medical check-up, dental examination, and carotid ultrasonography were studied. Carotid atherosclerosis was expressed as the maximum and mean carotid intima-media thickness (max-IMT, mean-IMT) and the presence of stenosis (≥75%). Periodontal status was examined by the Community Periodontal Index (CPI, codes 0-4). The participants were divided into three groups according to the periodontal status (CPI0-2, CPI3, CPI4). RESULTS: A positive correlation was found between mean-IMT and periodontal disease after adjustment for cardiovascular risk factors in the entire cohort (mean-IMT in hypertensives: CPI0-2: 0.848 mm, CPI3: 0.857 mm, CPI4: 0.877 mm; normotensives: 0.782, 0.802, 0.826). In the entire cohort, the multivariable-adjusted odds ratio of stenosis based on mean-IMT significantly increased according to periodontal status in normotensives (odds ratio; CPI0-2: 1, CPI3: 1.39, CPI4: 2.53; p-value for trend = .004) but showed only marginal significant increase in hypertensives (1, 1.15, 1.55; p-value for trend = .063). No significant relationships were observed for max-IMT in all analyses. CONCLUSION: We observed an association between periodontal disease and atherosclerosis in normotensive and hypertensive participants.

Feasibility of Flow Cytometry Analysis of Gastrointestinal Tract-Residing Lymphocytes in Hematopoietic Stem Cell Transplant Recipients.

The feasibility of lymphocyte isolation and flow cytometry using a single endoscopic biopsy specimen from the gastrointestinal tract of patients who have undergone hematopoietic stem cell transplantation has not been investigated. We acquired 51 endoscopic biopsy specimens from the gastrointestinal tract of 35 patients. We divided the flow cytometry samples into two groups: group A, successful lymphocyte isolation (n=24), and group B, incomplete isolation (n=27). We compared the backgrounds of the samples between the groups to reveal crucial elements in the successful isolation of lymphocytes residing in the gastrointestinal tract. Comparison between the groups revealed lymphocyte isolation success rates differed between biopsy sites. Isolation was most successful in samples from the duodenum (8/9, 88.9%), followed by the ileum (4/8, 50.0%), large intestine (4/11, 36.4%), and stomach (8/23, 34.8%). Tacrolimus was used more frequently in group B (92.6%) than in group A (62.5%) (p=0.015). Logistic regression analysis revealed that isolation from the duodenum or ileum was a significant factor for successful isolation, while tacrolimus use was not statistically significant. In conclusion, the duodenum and ileum are more suitable sites than the stomach and colorectum for acquiring samples for flow cytometry.

Force exerted on maxillary anterior teeth in mandibular unilateral and bilateral distal extension partial edentulous situation.

The purpose of this study was to determine the influence of mandibular unilateral and bilateral distal extension partial edentulous situation and the use of removable partial dental prostheses on the force exerted on maxillary anterior teeth. A commercially available jaw model with exchangeable teeth was used. Seven experimental conditions of mandibular distal extension edentulous situation were prepared and a distal extension removable partial dental prosthesis to replace missing posterior teeth was fabricated. The occlusal force was measured by inserting an occlusal force measuring film between the maxillary and mandibular teeth of the model. An occlusal load was applied and the forces and ratios were compared using the Kruskal-Wallis test and the Mann-Whitney U test (p < 0.05). As a result, the force exerted on the maxillary anterior teeth increased significantly as the number of remaining teeth decreased in unilateral and bilateral edentulous situation. The force exerted on the maxillary anterior teeth decreased significantly with use of a removable partial dental prosthesis. It is concluded that when the number of remaining teeth decreases in mandibular unilateral and bilateral distal extension partial edentulous situation, the burden on the maxillary anterior teeth increases. Our findings suggest that for patients with mandibular distal extension partial edentulous situation, using a removable partial dental prosthesis is effective in preserving the remaining teeth by reducing excessive force.