Macrophage depletion using clodronate liposomes reveals latent dysfunction of the hematopoietic microenvironment associated with persistently imbalanced M1/M2 macrophage polarization in a mouse model of hemophagocytic lymphohistiocytosis.

Hemophagocytic lymphohistiocytosis (HLH), a hyperinflammatory syndrome, is caused by the incessant activation of lymphocytes and macrophages, resulting in damage to organs, including hematopoietic organs. Recently, we demonstrated that repeated lipopolysaccharide (LPS) treatment induces HLH-like features in senescence-accelerated (SAMP1/TA-1) mice but not in senescence-resistant control (SAMR1) mice. Hematopoietic failure in LPS-treated SAMP1/TA-1 mice was attributed to hematopoietic microenvironment dysfunction, concomitant with severely imbalanced M1 and M2 macrophage polarization. Macrophages are a major component of the bone marrow (BM) hematopoietic microenvironment. Clodronate liposomes are useful tools for in vivo macrophage depletion. In this study, we depleted macrophages using clodronate liposomes to determine their role in the hematopoietic microenvironment in SAMP1/TA-1 and SAMR1 mice. Under clodronate liposome treatment, the response between SAMR1 and SAMP1/TA-1 mice differed as follows: (1) increase in the number of activated M1 and M2 macrophages derived from newly generated macrophages and M2-dominant and imbalanced M1 and M2 macrophage polarization in the BM and spleen; (2) severe anemia and thrombocytopenia; (3) high mortality rate; (4) decrease in erythroid progenitors and B cell progenitors in the BM; and (5) decrease in the mRNA expression of erythroid-positive regulators such as erythropoietin and increase in that of erythroid- and B lymphoid-negative regulators such as interferon-γ in the BM. Depletion of residual macrophages in SAMP1/TA-1 mice impaired hematopoietic homeostasis, particularly erythropoiesis and B lymphopoiesis, owing to functional impairment of the hematopoietic microenvironment accompanied by persistently imbalanced M1/M2 polarization. Thus, macrophages play a vital role in regulating the hematopoietic microenvironment to maintain homeostasis.

Fluoroalkyl Sulfoximines for Versatile Photocatalytic Radical Fluoroalkylations.

Fluoroalkyl sulfoximines, which serve as electron-accepting fluoroalkyl radical sources, are easy-to-handle, solid, and bench-stable chemicals. Fluoroalkyl radicals can be generated from sulfoximine reagents using strong one-electron injectors, such as a highly reducing photoredox catalyst in the excited state. Our group has developed photocatalytic radical di- and mono-fluoromethylation and α-monofluoroalkylation of olefins with the corresponding fluoroalkyl sulfoximines. In this personal account, appropriate combinations of fluoroalkyl sulfoximines and photoredox catalysts, leading to successful radical fluoroalkylation, have been discussed.

[Thrombotic microangiopathy with gastrointestinal hemorrhage during carfilzomib therapy for multiple myeloma].

A 70-year-old woman was admitted to the hospital with loss of appetite and melena. She was diagnosed with multiple myeloma 7 years ago and had been on carfilzomib, lenalidomide, and dexamethasone (KRd) therapy for a month because her disease had a relapsed/refractory. On admission, her laboratory tests revealed hemolytic anemia with schizocytes, thrombocytopenia, and acute renal dysfunction. TMA (thrombotic microangiography) caused by carfilzomib was suspected. The possibility of thrombotic thrombocytopenia was considered, and steroid pulse therapy was initiated. Her condition improved significantly after she stopped taking carfilzomib, plasma exchange, hemodiafiltration, steroid pulse therapy, and abstaining from food. The previously reported cases of carfilzomib-induced TMA included fever, gastrointestinal symptoms (nausea/vomiting, diarrhea), and acute renal disorders (lower extremity edema, decreasing urine output). As far as we know, this is the first case of carfilzomib-induced TMA with bleeding as the first symptom.

[Case of Tongue Cancer That Was Considered to Be a Metachronous Double Cancer with Parotid Gland Cancer].

In Japan, the incidence of double cancers is increasing due to the rise in cancer prevalence in the super-aging society, and the frequency is particularly high among patients with head and neck cancer. To the best of our knowledge, there has been only 1 reported case of metachronous double cancer with parotid gland cancer and tongue squamous cell carcinoma, and herein we report the outline of this case. The patient was a 70-year-old male with a smoking history. In 2017, a total parotidectomy and neck dissection for adenocarcinoma of the right parotid gland were performed at the otolaryngology department, followed by concurrent chemoradiotherapy as postoperative therapy. Pathological examination revealed adenocarcinoma NOS(pT4aN2bM0, Stage ⅣA). There was no recurrence or metastasis, and the patient was recovering well. However, in October 2022, the patient presented to the hospital with a chief complaint of pain at the right margin of the tongue. At the initial consultation, an ulcerative lesion with a slightly unclear boundary and maximum diameter of approximately 15 mm was observed on the right margin of the tongue. Since epithelialization was observed in some regions, it was diagnosed as intractable stomatitis and the patient was put under observation for the time being. With no signs of healing during the follow- up examination a month later and considering the possibility of malignant tumors, a total excision of tongue lesion was performed. Pathological examination revealed well-differentiated squamous cell carcinoma(pT1N0M0, Stage Ⅰ). Going forward, we plan to conduct careful follow-up observations with the possibility of further metachronous double cancer occurrences in mind.

Impact of human leukocyte antigen mismatch on outcomes after unrelated bone marrow transplantation in paediatric patients: A retrospective analysis by the JSTCT HLA working group.

The impact of human leukocyte antigen (HLA) mismatching at the HLA-A, -B, -C, and -DRB1 loci after unrelated bone marrow transplantation in paediatric patients with haematological malignancies has not been fully examined. Here, we analysed patients with haematological malignancies (all aged ≤15 years; n = 1330) who underwent a first unrelated bone marrow transplantation between 1993 and 2017 in Japan. The results show that although an HLA mismatch was significantly associated with a low relapse rate, it was also associated with higher non-relapse mortality. There was a significant association between HLA mismatch and low overall survival. Locus mismatch analysis revealed that, as in adults, an HLA-C mismatch had a significant negative impact on survival; however, in paediatric patients, an HLA-DRB1 mismatch did not have a negative impact, although these HLA mismatch effects are weakened in recent cases. Taken together, the results suggest that an HLA-matched donor should be the first candidate for paediatric patients; however, for patients without a matched sibling or matched unrelated donor, we can select an unrelated donor with a mismatch at HLA-DRB1 if available.

Hematopoietic Cell Transplantation for Inborn Errors of Immunity Other than Severe Combined Immunodeficiency in Japan: Retrospective Analysis for 1985-2016.

PURPOSE: Hematopoietic cell transplantation (HCT) is a curative therapy for most patients with inborn errors of immunity (IEI). We conducted a nationwide study on HCT for patients with IEI other than severe combined immunodeficiency (non-SCID) in Japan. METHODS: Data from the Japanese national database (Transplant Registry Unified Management Program, TRUMP) for 566 patients with non-SCID IEI, who underwent their first HCT between 1985 and 2016, were retrospectively analyzed. RESULTS: The 10-year overall survival (OS) and event-free survival (EFS) were 74% and 64%, respectively. The 10-year OS for HCT from unrelated bone marrow (URBM), accounting for 39% of HCTs, was comparable to that for HCT from matched sibling donor (MSD), 79% and 81%, respectively. HCT from unrelated cord blood (URCB), accounting for 28% of HCTs, was also common, with a 10-year OS of 69% but less robust engraftment. The intensity of conditioning was not associated with OS or neutrophil recovery; however, myeloablative conditioning was more frequently associated with infection-related death. Patients who received myeloablative irradiation showed poor OS. Multivariate analyses revealed that HCT in 1985-1995 (hazard ratio [HR], 2.0; P = 0.03), URCB (HR, 2.0; P = 0.01), and related donor other than MSD (ORD) (HR, 2.9; P < 0.001) were associated with poor OS, and URCB (HR, 3.6; P < 0.001) and ORD (HR, 2.7; P = 0.02) showed a higher incidence of retransplantation. CONCLUSIONS: We present the 1985-2016 status of HCT for non-SCID IEI in Japan with sufficient statistical power, highlighting the potential of URBM as an alternative donor and the feasibility of reduced intensity conditioning.

Allergic Sensitization Is Crucial for the Suppressive Role of Streptococcus pneumoniae in the Acute Exacerbation of Asthma.

INTRODUCTION: Allergic sensitization is an important factor in the development, severity, and exacerbation of asthma, which is attributed to type 2 (T2) inflammation. Evidence suggests that respiratory bacterial pathogens (e.g., Streptococcus pneumoniae) exert suppressive effects on airway T2 inflammation. To clarify the role of allergic inflammation in bacterial colonization in asthma based on allergic sensitization, we investigated pharyngeal bacterial colonization, biomarkers (e.g., serum eosinophil cationic protein (ECP) and cytokines/chemokines), and symptoms in the acute exacerbation of childhood asthma. METHODS: Pharyngeal samples were collected from 53 children (mean/median age 2.7/2.5 years). Serum levels of total and allergen-specific IgE against aeroallergens, ECP, and 17 cytokines/chemokines were measured. RESULTS: Allergic sensitization was recognized in 62.2% patients. S. pneumoniae, Moraxella catarrhalis, Haemophilus influenzae, and other bacteria were detected in 47.1%, 11.3%, 11.3%, and 30.1% of all patients, respectively. Patients with S. pneumoniae had a significantly shorter duration of wheezing than those without (4.7 ± 3.6 vs. 7.1 ± 3.5 days, p = 0.024). In patients with allergic sensitization, patients with S. pneumoniae had a significantly shorter duration of wheezing than those without (4.0 ± 3.6 vs. 7.7 ± 4.0 days, p = 0.003). Serum total IgE was significantly lower in patients with S. pneumoniae than in those without (81.9 [7.8-894] vs. 287 [4.4-1,840] IU/mL, p = 0.014). Serum ECP was significantly higher (33.1 [2-109] vs. 7.8 [3-35] ng/mL, p = 0.042), and IFN-γ was significantly lower (5.6 [4-10] vs. 16.4 [7-28] pg/mL, p = 0.032) in patients with allergic sensitization than those without. DISCUSSION/CONCLUSION: Our results suggested that the suppressive effects of S. pneumoniae colonization were observed only in patients with allergic sensitization, wherein serum total IgE, ECP, and IFN-γ may have an important role on acute exacerbation of asthma.

Antibiotic Treatments Prolong the Wheezing Period in Acute Exacerbation of Childhood Bronchial Asthma.

INTRODUCTION: Although current guidelines recommend against routine antibiotic prescription for acute exacerbation of bronchial asthma, children with acute exacerbation of asthma receive antibiotic treatment more frequently. In addition, those antibiotics are often prescribed only for exacerbation of asthma without concurrent bacterial infection. OBJECTIVE: To clarify the association between antibiotic treatment and bacterial colonization in acute exacerbation of asthma, we investigated whether or not antibiotics affect the clinical condition, laboratory findings, and pharyngeal bacterial colonization in those patients. METHODS: Potential bacterial pathogens were investigated in pharyngeal samples of 111 children with acute exacerbation of asthma (mean/median age: 2.8/2.6 years old, respectively). We collected clinical data, such as the duration of wheezing and antibiotic use, and measured the peripheral white blood cell counts, C-reactive protein, and serum levels of total and allergen-specific IgE. RESULTS: Antibiotics were used in 50.5% patients with acute asthma exacerbation and included cephalosporin, penicillin, macrolide, and others. Episodes of wheezing were significantly longer in patients with antibiotic treatment than in those without it (6.7 ± 3.6 days vs. 6.0 ± 3.1, p = 0.044). Similarly, episodes of wheezing were significantly longer in moderate exacerbation patients with antibiotics than in those without them. Furthermore, in patients with Streptococcus pneumoniae, antibiotic treatment was associated with an extended duration of wheezing in cases of acute moderate exacerbation (7.0 ± 2.4 days vs. 4.8 ± 4.1, p = 0.043). CONCLUSIONS: These results suggest that antibiotic treatment in acute exacerbation of asthma might lead to longer asthmatic symptoms, specifically in patients with pharyngeal S. pneumoniae colonization.

Relationship between Carnitine Deficiency and Tyrosine Kinase Inhibitor Use in Patients with Chronic Myeloid Leukemia.

BACKGROUND: Some chemotherapeutic agents cause carnitine deficiency, which causes general fatigue. However, there is no study on carnitine deficiency in patients with chronic myeloid leukemia (CML) during tyrosine kinase inhibitor (TKI) therapy. OBJECTIVE: In this study, we investigated carnitine concentrations in patients with CML receiving TKI therapy. METHOD: This study included patients with well-controlled CML. Total carnitine and free carnitine concentrations were evaluated using the enzyme cycling method. The brief fatigue inventory (BFI) and cancer fatigue scale (CFS) were used to assess general fatigue developed during TKI therapy. RESULTS: Fifty-five patients on TKI therapy were included. Of these, 12 (21.8%) patients had low free carnitine concentrations. Free carnitine concentrations were higher in men than in women. Younger age was closely associated with lower free carnitine concentrations. TKI type, TKI dose, treatment response, or therapy duration were not associated with free carnitine concentrations. None of the scores (the global fatigue score with the BFI and CFS score) correlated with carnitine concentrations. Concentrations of free carnitine in patients in the treatment-free remission group were slightly higher than those in the TKI group, with only 9.1% having a low concentration of free carnitine. CONCLUSION: Carnitine deficiency is probably not a major cause of general fatigue but may occur in patients with CML receiving TKI therapy.

[Surgical Treatment of Maxillary Gingival Carcinoma with Mental Retardation-A Case Report].

Many patients with mental retardation have a limited awareness of abnormalities in the oral cavity, making early detection of oral cancer difficult. Moreover, during examination and treatment, these patients may not understand well-intentioned verbal explanations and may express their anxiety through nonverbal communication. Herein we discuss a case in which favorable results were obtained when surgical treatment was performed on a maxillary gingival carcinoma patient with mental retardation. The patient was a 61-year-old man who was admitted to our hospital with maxillary gingival pain. A biopsy revealed well-differentiated oral squamous cell carcinoma(cT4aN0M0, Stage ⅣA). Hemi-maxillectomy was performed and postoperative recovery was uneventful. A maxillary prosthesis was provided for oral rehabilitation. At the 5-year follow-up, there were no signs of recurrence or metastasis. This case illustrates the importance of collaboration between oral maxillofacial surgeons and specialists from related departments for the comprehensive management of patients with mental retardation.

Hematopoietic Cell Transplantation for Severe Combined Immunodeficiency Patients: a Japanese Retrospective Study.

PURPOSE: Hematopoietic cell transplantation (HCT) is a curative therapy for patients with severe combined immunodeficiency (SCID). Here, we conducted a nationwide study to assess the outcome of SCID patients after HCT in Japan. METHODS: A cohort of 181 SCID patients undergoing their first allogeneic HCT in 1974-2016 was studied by using the Japanese national database (Transplant Registry Unified Management Program, TRUMP). RESULTS: The 10-year overall survival (OS) of the patients who received HCT in 2006-2016 was 67%. Umbilical cord blood (UCB) transplantation was performed in 81 patients (45%). The outcomes of HCT from HLA-matched UCB (n = 21) and matched sibling donors (n = 22) were comparable, including 10-year OS (91% vs. 91%), neutrophil recovery (cumulative incidence at 30 days, 89% vs. 100%), and platelet recovery (cumulative incidence at 60 days, 89% vs. 100%). Multivariate analysis of the patients who received HCT in 2006-2016 demonstrated that the following factors were associated with poor OS: bacterial or fungal infection at HCT (hazard ratio (HR): 3.8, P = 0.006), cytomegalovirus infection prior to HCT (HR: 9.4, P = 0.03), ≥ 4 months of age at HCT (HR: 25.5, P = 0.009), and mismatched UCB (HR: 19.8, P = 0.01). CONCLUSION: We showed the potential of HLA-matched UCB as a donor source with higher priority for SCID patients. We also demonstrated that early age at HCT without active infection is critical for a better prognosis, highlighting the importance of newborn screening for SCID.

[Functional Recovery following Incisional Cheiloplasty for Lower Labial Edema That Developed after Bilateral Neck Dissection and Postoperative Chemoradiotherapy-A Case Report].

We report a case of functional recovery following incisional cheiloplasty for the management of lower labial edema that developed after bilateral neck dissection with preservation of the one-side internal jugular vein and postoperative chemoradiotherapy. An 81-year-old woman underwent partial maxillectomy for the treatment of maxillary gingival cancer(squamous cell carcinoma, cT1N0M0, Stage Ⅰ)in April 2013. In July 2013, she underwent bilateral neck dissection(right, modified; left, radical)for bilateral cervical lymph node recurrence with an extra-nodal spread and received postoperative chemoradiotherapy( CDDP 75 mg/m2×3 course and total radiotherapy dosage of 66 Gy). Thereafter, the patient's condition progressed without recurrence or metastasis; however, the lower labium became edematous, and severe labial dysfunction was observed. Therefore, lower labial incisional cheiloplasty was performed under local anesthesia in October 2020. An excision area of 160×14 mm was determined on the inner side of the lower labium, and excision was performed with a steel blade scalpel. Lip closure became possible one week after the operation. Seven months after the operation, the patient recovered labial function and was satisfied with the outcome.

[Mass Screening of Oral Cancer in Eastern Shimane Prefecture during 2015-2019].

The Department of Oral and Maxillofacial Surgery, Shimane University Faculty of Medicine, has been conducting mass screening of oral cancer using oral abrasion cytology by oral surgeons in eastern Shimane prefecture for public awareness and its early detection. As a result, 3(0.09%)cases of oral cancer were identified. Case 1: The patient was diagnosed with well-differentiated squamous cell carcinoma in the floor of the mouth(pT1N0M0, Stage Ⅰ)after undergoing Matsue city oral cancer screening in 2016. Case 2: The patient underwent oral cancer screening in Izumo city in 2018 and was diagnosed with verrucous carcinoma in the back of the tongue(pT1N0M0, Stage Ⅰ). Case 3: The patient was diagnosed with highly differentiated squamous cell carcinoma of the palate(pT1N0M0, Stage Ⅰ)after undergoing the Izumo city oral cancer screening in 2019. Awareness of oral cancer is important, and cancer screening by oral surgeons using cytology is highly useful and should be continued in the future.

[A Case of Treatment Applicable to Squamous Cell Carcinoma of the Tongue by Mass Screening Examination of Oral Cancer in Western Part of the Shimane Prefecture].

Radical excision, a common oral cancer treatment, produces variable postoperative results depending on the specialized tissues involved and the extent of the cancer. Furthermore, the material selected for reconstruction also influences functional outcomes. Oral dysfunction due to postoperative tissue loss is more common with advanced cancer; therefore, early detection and treatment are important. To improve oral cancer awareness and early detection, mass oral cancer screenings led by maxillofacial surgeons in cooperation with the Shimane prefecture and local dental associations were conducted. We describe the mass screening methods and describe a case of tongue cancer that was detected and treated as a result of our screening efforts.

Chemistry of Tertiary Carbon Center in the Formation of Congested C-O Ether Bonds.

Nucleophilic substitutions, including SN 1 and SN 2, are classical and reliable reactions, but a serious drawback is their intolerance for both bulky nucleophiles and chiral tertiary alkyl electrophiles for the synthesis of a chiral quaternary carbon center. An SRN 1 reaction via a radical species is another conventional method used to carry out substitution reactions of bulky nucleophiles and alkyl halides, but chiral tertiary alkyl electrophiles cannot be used. Therefore, a stereospecific nucleophilic substitution reaction using chiral tertiary alkyl electrophiles and bulky nucleophiles has not yet been well studied. In this paper, we describe the reaction of tertiary alkyl alcohols and non-chiral or chiral α-bromocarboxamides as a tertiary alkyl source for the formation of congested ether compounds possessing two different tertiary alkyl groups on the oxygen atom with stereoretention.

Prevalence of germline GATA2 and SAMD9/9L variants in paediatric haematological disorders with monosomy 7.

Monosomy 7 (-7) occurs in various types of paediatric myeloid disorders and has a poor prognosis. Recent studies have demonstrated that patients with germline gain-of-function SAMD9/9L variants and loss-of-function GATA2 variants are prone to developing myelodysplastic syndrome (MDS) associated with -7. However, the prevalence of the genetic variants among paediatric haematologic disorders with -7 is unknown. The present study screened germline variants of GATA2 and SAMD9/9L in 25 patients with various types of paediatric haematological disorders associated with -7. The diagnoses of the 25 patients included MDS (n = 10), acute myeloid leukaemia (AML) and myeloid sarcomas (n = 9), juvenile myelomonocytic leukaemia (n = 3) and other disorders (n = 3). Seven patients with a germline pathogenic GATA2 variant were found. For SAMD9/9L screening, next-generation sequencing was used to detect low-abundance variants and found four novel germline variants. Functional analysis revealed that three out of the four variants showed growth-restricting capacity in vitro and thus, were judged to be pathogenic. Cases with GATA2 mutation tended to be older, compared to those with SAMD9/9L mutations. In conclusion, GATA2 and SAMD9/9L were sequenced in 25 patients with paediatric haematologic disorders associated with -7, and 40% of them were found to have some pathogenic germline variants in the three genes.

The Suppressive Role of Streptococcus pneumoniae Colonization in Acute Exacerbations of Childhood Bronchial Asthma.

INTRODUCTION: Little is known about the association between bacterial infections and exacerbations of bronchial asthma. OBJECTIVE: To elucidate the effect of bacterial infections on bronchial asthma, we examined pharyngeal bacterial colonization, duration of wheezing, and serum levels of cytokines and chemokines during acute exacerbations of asthma in children. METHODS: Potential bacterial pathogens were investigated in pharyngeal samples and viruses obtained from nasal secretions of 111 children who were outpatients and/or in patients with acute exacerbations of asthma (mean/median age: 2.8/2.6, respectively). We also measured serum levels of 27 different cytokines/chemokines. RESULTS: Pharyngeal bacterial cultures were positive in 110 of 111 children. The 3 major bacterial pathogens were Streptococcus pneumoniae (29.7%), Moraxella catarrhalis (11.7%), and Haemophilus influenzae (10.8%). M. catarrhalis was detected more frequently in patients with pneumonia. Furthermore, patients with S. pneumoniae colonization had significantly shorter wheezing episodes than those without it. In contrast, the duration of wheezing did not differ significantly among cases with other bacteria such as M. catarrhalis and H. influenzae. Furthermore, the length of wheezing episode in patients with S. pneumoniae colonization showed significant inverse correlation with peripheral white blood cell count, neutrophil count, and C-reactive protein, while there was no significant correlation between duration of wheezing and these 3 parameters among patients with M. catarrhalis or H. influenza. Among the 27 cytokines/chemokines, only serum tumor necrosis factor (TNF)-α was significantly lower in patients with S. pneumoniae colonization than in those without it. CONCLUSIONS: These results suggested that pharyngeal S. pneumoniae colonization plays a suppressive role on the pathophysiology during acute exacerbations of asthma.

Laser Flash Photolysis Studies on Radical Monofluoromethylation by (Diarylamino)naphthalene Photoredox Catalysis: Long Lifetime of the Excited State is Not Always a Requisite.

Organic photoredox catalysis has become a useful tool for the development of metal-free radical reactions. Recently, we have reported that 1,4-bis(diphenylamino)naphthalene N serves as an efficient photoredox catalyst for radical monofluoromethylation with N-tosyl-S-monofluoromethyl-S-phenylsulfoximine 2. In this paper, we report the preparation and photo- and electrochemical properties of (diarylamino)naphthalene derivatives, 1,4-bis(di(p-tert-butylphenyl)amino)naphthalene 1a, 1,5-bis(di(p-tert-butylphenyl)amino)naphthalene 1b, and 1-(di(p-tert-butylphenyl)amino)naphthalene) 1c, as supported by density functional theory (DFT) and time-dependent-DFT calculations. In addition, their performance of photocatalysis has been evaluated by means of methoxy-monofluoromethylation of aromatic alkenes. Laser flash photolysis shows that the fluorescence of 1a in the excited state is efficiently quenched by 2 (quenching rate constant kq = ca. 2 × 109 M-1 s-1). Transient absorption spectroscopic analyses reveal that the excited species of 1a in the presence of 2 starts decreasing in ca. 100 ps, suggesting the occurrence of fast electron-transfer processes. These results lead to the unconventional concept for the catalyst design, that is, long lifetime of the excited state is not always a requisite for efficient photoredox catalysts.

Retention force and allowable range of the angle of an implant-supported overdenture attachment system using healing screws and a silicone resilient denture liner.

STATEMENT OF PROBLEM: Changes in the intraoral condition immediately after implant placement and in patients using fixed prosthetic appliances with implant abutments cause problems that require the use of an easily adjustable implant-supported overdenture system. PURPOSE: The purpose of this in vitro study was to develop a simulated implant-supported overdenture attachment system by using healing screws for the patrix and a silicone resilient denture liner for the matrix and to investigate the initial retention force, time-course changes, and allowable range of the angle between attachments. MATERIAL AND METHODS: Tests on the retention force and allowable range of the angle were performed. Attachments using tissue-level healing screws (height: 2.0 and 3.0 mm) for the patrix and a silicone resilient denture liner for the matrix were prepared. In the retention force measurement test, the frequency of insertion and removal was set at 3 per day to simulate a 4-month relief period. The joined attachment model was pulled apart, and the maximum traction (N) required to remove it was defined as the retention force. The retention force was measured every 90 times (representing the number of insertions and removals per month). To test the allowable angle range, 2 patrices were used. The angle between the 2 patrices was set at 0, 10, 20, and 30 degrees, and the angular limit for joining with the matrix was measured. The initial retention force of the healing screw attachments was compared with that of a polymeric O-ring by using 1-way layout ANOVA followed by the Bonferroni test (α=.05). To analyze time-course changes in the 2 types of healing screw attachments, the retention force before insertion and removal was compared with that after repeated insertions and removals for each simulated period using 1-way layout ANOVA followed by the Dunnett test (α=.05). RESULTS: The initial retention force of the 2.0- and 3.0-mm healing screws was 2.4 ±0.1 and 2.6 ±0.2 N. After repeating insertions and removals to simulate use for 4 months, the retention force of the 2.0- and 3.0-mm healing screws was 1.8 ±0.2 and 2.2 ±0.1 N, respectively, both showing significant differences from the initial retention force (P<.05). The allowable angle range test revealed that insertion and removal of the healing screws was possible up to 30 degrees. CONCLUSIONS: Under the conditions of this in vitro study, repeated insertion and removal attenuated the retention force but was still equivalent to the retention force of the O-ring. The allowable range of the angle between patrices for insertion and removal was up to 30 degrees.

[Transformation of CD5-positive nodal marginal zone lymphoma to diffuse large B-cell lymphoma].

Nodal marginal zone lymphoma (NMZL) is a form of nodal B-cell lymphoma exhibiting proliferation of abnormal lymphocytes at the circumference of the mantle zone in the lymph nodes. Although the outcome of patients with this disease is often favorable, we recently encountered a patient with a CD5-positive NMZL who was resistant to chemotherapy. A 67-year-old woman complaining of systemic lymph node swelling was referred to our hospital. After biopsy of the neck lymph node, she was diagnosed with CD5-positive NMZL. Disease progression was revealed after 16 months, and she was initially treated with chemotherapy consisting of rituximab, cyclophosphamide, vincristine, and prednisolone (R-CVP). However, this therapy was ineffective. Subsequent therapy with rituximab and bendamustine also failed to induce remission. A rebiopsy revealed that the NMZL had transformed into a diffuse large B-cell lymphoma. This patient died after 2 years from the initial diagnosis due to lymphoma progression. Cases of CD5-positive NMZL are rare; thus, it is difficult to study the clinical implications of CD5 expression in this disease. Here we describe the current understanding of CD5 expression in NMZL.