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1.
Ann Med Surg (Lond) ; 86(4): 2176-2180, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38576969

RESUMO

Introduction and importance: Infections of inferior vena cava (IVC) filters are rare. The authors present a case of IVC filter infection following concurrent emphysematous urinary tract infections that was finally treated with prolonged suppressive antibiotic therapy (PSAT). Case presentation: A 68-year-old man with pemphigoid and type 2 diabetes mellitus, who had undergone IVC filter placement, was transferred with decreased consciousness, respiratory failure, and hypotension. Computed tomography revealed gas in the left renal parenchyma and bladder wall, suggesting a diagnosis of concurrent emphysematous pyelonephritis and cystitis. While blood and urine cultures were positive for extended-spectrum beta-lactamase-producing Escherichia coli, and the patient's general condition improved with proper antibiotic therapy, bacteremia persisted until day 10 from symptom onset. After ruling out abscesses and infectious endocarditis, the cause of persistent bacteremia was suspected to be IVC filter infection. As the IVC had been placed 12 years before, the authors did not remove it to avoid complications. PSAT with sulfamethoxazole-trimethoprim was continued after 6 weeks of intravenous antibiotic therapy. The patient had an uneventful course over the year following hospital discharge. Clinical discussion: PSAT is considered for device-related infections in patients with cardiac assist devices and artificial joints when the infection flares up or recurs even after antibiotic treatment of an adequate duration. There is no consensus regarding the optimal duration of antimicrobial therapy for IVC filter infections. Conclusion: Infections of implanted devices, such as IVC filters, secondary to severe infections can cause persistent bacteremia. PSAT may be an alternative option to treat IVC filter infection, when the IVC filter is considered difficult to remove.

2.
Sci Rep ; 14(1): 7412, 2024 03 28.
Artigo em Inglês | MEDLINE | ID: mdl-38548914

RESUMO

Peritoneal membrane dysfunction in peritoneal dialysis (PD) is primarily attributed to angiogenesis; however, the integrity of vascular endothelial cells can affect peritoneal permeability. Hyaluronan, a component of the endothelial glycocalyx, is reportedly involved in preventing proteinuria in the normal glomerulus. One hypothesis suggests that development of encapsulating peritoneal sclerosis (EPS) is triggered by protein leakage due to vascular endothelial injury. We therefore investigated the effect of hyaluronan in the glycocalyx on peritoneal permeability and disease conditions. After hyaluronidase-mediated degradation of hyaluronan on the endothelial cells of mice, macromolecules, including albumin and ß2 microglobulin, leaked into the dialysate. However, peritoneal transport of small solute molecules was not affected. Pathologically, hyaluronan expression was diminished; however, expression of vascular endothelial cadherin and heparan sulfate, a core protein of the glycocalyx, was preserved. Hyaluronan expression on endothelial cells was studied using 254 human peritoneal membrane samples. Hyaluronan expression decreased in patients undergoing long-term PD treatment and EPS patients treated with conventional solutions. Furthermore, the extent of hyaluronan loss correlated with the severity of vasculopathy. Hyaluronan on endothelial cells is involved in the peritoneal transport of macromolecules. Treatment strategies that preserve hyaluronan in the glycocalyx could prevent the leakage of macromolecules and subsequent related complications.


Assuntos
Diálise Peritoneal , Fibrose Peritoneal , Humanos , Animais , Camundongos , Ácido Hialurônico/metabolismo , Células Endoteliais , Diálise Peritoneal/efeitos adversos , Peritônio/metabolismo , Transporte Biológico , Soluções para Diálise/metabolismo , Fibrose Peritoneal/etiologia , Fibrose Peritoneal/metabolismo
3.
Genes (Basel) ; 15(3)2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38540372

RESUMO

In newborn screening (NBS), it is important to consider the availability of multiplex assays or other tests that can be integrated into existing systems when attempting to implement NBS for new target diseases. Recent developments in innovative testing technology have made it possible to simultaneously screen for severe primary immunodeficiency (PID) and spinal muscular atrophy (SMA) using quantitative real-time polymerase chain reaction (qPCR) assays. We describe our experience of optional NBS for severe PID and SMA in Osaka, Japan. A multiplex TaqMan qPCR assay was used for the optional NBS program. The assay was able to quantify the levels of T-cell receptor excision circles and kappa-deleting recombination excision circles, which is useful for severe combined immunodeficiency and B-cell deficiency screening, and can simultaneously detect the homozygous deletion of SMN1 exon 7, which is useful for NBS for SMA. In total, 105,419 newborns were eligible for the optional NBS program between 1 August 2020 and 31 August 2023. A case each of X-linked agammaglobulinemia and SMA were diagnosed through the optional NBS and treated at early stages (before symptoms appeared). Our results show how multiplex PCR-based NBS can benefit large-scale NBS implementation projects for new target diseases.


Assuntos
Atrofia Muscular Espinal , Triagem Neonatal , Recém-Nascido , Humanos , Triagem Neonatal/métodos , Reação em Cadeia da Polimerase em Tempo Real/métodos , Homozigoto , Japão , Deleção de Sequência , Atrofia Muscular Espinal/diagnóstico , Atrofia Muscular Espinal/genética
4.
Eur J Appl Physiol ; 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38427101

RESUMO

PURPOSE: To clarify the association between forced expiration and the abdominal muscles by assessing the relationship between expiratory mouth pressure and abdominal muscle activity in healthy young males. METHODS: Twenty-five males underwent forced expiration at 20, 30, 50, 75, and 100% of the maximal expiratory mouth pressure. Mouth pressure was measured using a bridge-type transducer connected to a mouth pressure meter. Abdominal crunch, twist crunch, and abdominal hollowing at maximal voluntary contraction were also performed. During forced expiration and abdominal exercises, the activity of the rectus abdominis (RA), oblique externus abdominis/oblique internus abdominis (OE/OI), and OI/transversus abdominis (OI/TrA) was measured using surface electromyography. RESULTS: The determination coefficient (r2) for the linear relationship between mouth pressure and abdominal muscle activity was 0.86 ± 0.15 for the RA, 0.93 ± 0.06 for the OE/OI, and 0.90 ± 0.14 for the OE/OI. The slope of the linear relationship with r2 ≥ 0.50 showed no significant difference between the RA (0.22 ± 0.27) and the OE/OI (0.27 ± 0.21). However, it was significantly greater in the OI/TrA (1.78 ± 1.41) than in the RA and OE/OI. The OE/OI activity was significantly lower in the maximal forced expiration than in twist crunch, and the OI/TrA activity was not significantly greater in the maximal forced expiration than in twist crunch. CONCLUSION: All abdominal muscles contribute to forced expiration with a greater contribution of the OI and TrA than the RA and OE. Furthermore, the contribution of the TrA would be greater than that of the OI.

5.
J Allied Health ; 53(1): 51-57, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38430497

RESUMO

Resistance training is considered the most effective intervention for increasing older people's muscle mass and strength. Thus, we created the Sukubara®, a self-administered training system (squat + balance training) that incorporates a new low-load exercise. In this study, we hypothesize that introducing Sukubara will positively affect skeletal muscle mass and physical function. A preliminary verification was carried out on healthy, non-elderly participants who were recruited from the hospital staff. Participants were randomly assigned to two groups for a 12-week intervention: the resistance training group (R group) that performed the Sukubara exercise program and the control group (C group) that did not. This study's primary end¬point was a change in skeletal muscle mass, while the secondary endpoints were knee extension strength and one-leg standing time with eyes closed. An analysis of the 18 participants (R group = 8; C group = 10) was performed. Results showed that skeletal muscle mass, knee extension strength, and one-leg standing time were significantly improved or tended to be significantly higher in the R group than in the C group. Our study concluded that, by incorporating low-load exercise, Sukubara resulted in muscle hypertrophy and improved physical function.


Assuntos
Fragilidade , Autogestão , Mídias Sociais , Humanos , Idoso , Pessoa de Meia-Idade , Força Muscular/fisiologia , Projetos Piloto
6.
Geriatrics (Basel) ; 9(1)2024 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-38392107

RESUMO

This study examined whether SUKUBARA®, a remotely managed training system that we developed, could improve skeletal muscle mass and muscle strength in community-dwelling older adults. SUKUBARA® is a composite exercise program that combines lower-load resistance training and balance exercises. Participants were instructed to exercise while watching individually assigned videos on YouTube, such that the research administrators could verify the viewing records of each participant. Fifteen participants (69 ± 4 years) were randomly assigned to the intervention (eight participants; the RT group) or the control group (seven participants; the CO group). The primary endpoint was a change in fat-free mass (FFM; kg), whereas the secondary endpoints included a change in knee extension strength (KES; Nm/kg). Correlation analyses were conducted to examine the relationship between FFM and KES. During the 12-week intervention period, significant differences were observed between the RT and CO groups in the changes in FFM (0.5 ± 0.5 vs. -0.1 ± 0.5) and KES (0.20 ± 0.22 vs. 0.02 ± 0.13), and significant positive correlations were found between the changes. Thus, SUKUBARA®-based interventions have the potential to improve muscle hypertrophy and enhance muscle strength among community-dwelling older adults. Thus, SUKUBARA® -based interventions show promise in improving muscle hypertrophy and enhance muscle strength among community-dwelling older adults. However, appropriately powered future research is needed to replicate these findings.

7.
J Strength Cond Res ; 2024 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-38349337

RESUMO

ABSTRACT: Tanji, F, Ohnuma, H, Ando, R, Yamanaka, R, Ikeda, T, and Suzuki, Y. Longer ground contact time is related to a superior running economy in highly trained distance runners. J Strength Cond Res XX(X): 000-000, 2023-Running economy is a key component of distance running performance and is associated with gait parameters. However, there is no consensus of the link between the running economy (RE), ground contact time, and footstrike patterns. Thus, this study aimed to clarify the relationship between RE, ground contact time, and thigh muscle cross-sectional area (CSA) in highly trained distance runners and to compare these parameters between 2 habitual footstrike patterns (midfoot vs. rearfoot). Seventeen male distance runners ran on a treadmill to measure RE and gait parameters. We collected the CSAs of the right thigh muscle using a magnetic resonance imaging scanner. The RE had a significant negative relationship with distance running performance (r = -0.50) and ground contact time (r = -0.51). The ground contact time had a significant negative relationship with the normalized CSAs of the vastus lateralis muscle (r = -0.60) and hamstrings (r = -0.54). No significant differences were found in RE, ground contact time, or normalized CSAs of muscles between midfoot (n = 10) and rearfoot (n = 7) strikers. These results suggest that large CSAs of knee extensor muscles results in short ground contact time and worse RE. The effects of the footstrike pattern on the RE appear insignificant, and the preferred footstrike pattern can be recommended for running in highly trained runners.

8.
Tohoku J Exp Med ; 262(3): 163-171, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38220168

RESUMO

As pancreatic ductal adenocarcinoma (PDAC) is extremely malignant and refractory, therapeutic options for this cancer are anticipated worldwide. We isolated vasohihibin-2 (VASH2) and observed its overexpression in various types of cancer. We then noticed that upregulated expression of VASH2 in patients with PDAC resulted in a conspicuous reduction in the postoperative survival period and further revealed that the abrogation of Vash2 expression in pancreatic cancer cells inhibited its growth and metastasis and augmented tumor infiltration of CD8+ cells in the mouse model. We developed VASH2-targeting therapies, 2',4'-BNA-based antisense oligonucleotide targeting VASH2 (VASH2-ASO) as a nucleotide-based therapy, and VASH2-peptide vaccine as an antibody-based therapy. We also showed that the VASH2-peptide vaccine inhibited PDAC metastasis in an orthotopic mouse model. Here, we expanded our analysis of the efficacy of VASH2-targeting therapies for PDAC. VASH2-ASO treatment inhibited the growth of primary tumors by reducing tumor angiogenesis, normalizing tumor vessels, preventing ascites accumulation and distant metastasis to the liver and lungs, and augmenting the infiltration of CD8+ cells in metastatic tumors. VASH2-peptide vaccine did not affect the infiltration of CD8+ cells into tumors. The present study revealed that VASH2-targeting therapies are promising options for the treatment of PDAC. VASH2-ASO therapy can be administered at any stage of PDAC. Because of the increase of CD8+ cell infiltration, the combination therapy with immune checkpoint inhibitors may be an attractive option. The VASH2-peptide vaccine therapy may be useful for preventing metastasis and/or recurrence after successful initial treatment.


Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Camundongos , Animais , Humanos , Linhagem Celular Tumoral , Carcinoma Ductal Pancreático/patologia , Neoplasias Pancreáticas/terapia , Neovascularização Patológica , Proteínas Angiogênicas/metabolismo
9.
Cells ; 13(2)2024 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-38247803

RESUMO

Cancer-specific CD8+ cytotoxic T cells play important roles in preventing cancer growth, and IFN-γ, in addition to IL-12 and type I interferon, is critical for activating CD8+ cytotoxic T cells. We recently identified the capability of the amino-terminus region of dense granule protein 6 (GRA6Nt) of Toxoplasma gondii, an intracellular protozoan parasite, to activate IFN-γ production of microglia, a tissue-resident macrophage population. Therefore, in the present study, we examined whether recombinant GRA6Nt protein (rGRA6Nt) functions as an effective adjuvant to potently activate cancer-specific protective immunity using a murine model of MC38 colorectal cancer (CRC). When mice were immunized with non-replicable (either treated with mitomycin C or irradiated by X-ray) MC38 CRC cells in combination with rGRA6Nt adjuvant and received a challenge implantation of replication-capable MC38 tumor cells, those mice markedly inhibited the growth of the implanted tumors in association with a two-fold increase in CD8+ T cell density within the tumors. In addition, CD8+ T cells of the immunized mice secreted significantly increased amounts of granzyme B, a key mediator of the cytotoxic activity of CD8+ T cells, and IFN-γ in response to MC38 CRC cells in vitro when compared to the T cells from unimmunized mice. Notably, the protective effects of the immunization were specific to MC38 CRC cells, as the immunized mice did not exhibit a significantly inhibited growth of EL4 lymphoma tumors. These results indicate that rGRA6Nt is a novel and effective protein adjuvant when used in immunizations with non-replicable cancer cells to potently activate the protective immunity specifically against the cancer cells employed in the immunization.


Assuntos
Neoplasias Colorretais , Parasitos , Animais , Camundongos , Linfócitos T CD8-Positivos , Modelos Animais de Doenças , Imunização , Adjuvantes Imunológicos/farmacologia , Adjuvantes Farmacêuticos
10.
Pediatr Infect Dis J ; 43(4): 313-319, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38134374

RESUMO

BACKGROUND: In Japan, the incidence of subacute sclerosing panencephalitis (SSPE) has reduced; however, the medical conditions and factors associated with disease progression remain unclear. METHODS: A nationwide survey of SSPE was conducted using a questionnaire in 2022. We conducted a descriptive analysis of the patients with SSPE in 2022 and Cox proportional hazards analyses for disease progression. We compared the patients with SSPE with those in a 2007 survey. RESULTS: A total of 37 surviving patients with SSPE were enrolled [median age: 32 years (range: 16-52 years)]. No new cases have been identified since 2017 in the survey. Jabbour stage IV was the most common stage (66.7%). The hazard ratios (95% confidence intervals) of male sex and age at the time of measles infection (years) were 2.56 (1.13-5.76) and 0.57 (0.34-0.93), respectively. Compared with those in 2007, the proportion of patients in hospitals decreased from 13.7% to 2.7%, whereas that of patients in nursing facilities increased from 17.6% to 29.7%. The proportions of patients prescribed inosine pranobex, interferon and ribavirin at the time of the survey decreased from 96.1% to 79.4%, 74.8% to 14.3% and 25.3% to 0%, respectively. The proportions of patients with gastrostomy, tracheostomy and ventilator use increased from 5.9% to 69.7%, 23.3% to 60.0% and 10.8% to 32.4%, respectively. CONCLUSIONS: Decreased measles cases in Japan reduced new SSPE cases. However, surviving patients in 2022 had advanced disease stages and needed medical care. Male sex and early measles infection were significantly associated with disease progression.


Assuntos
Sarampo , Panencefalite Esclerosante Subaguda , Humanos , Masculino , Adulto , Panencefalite Esclerosante Subaguda/epidemiologia , Japão/epidemiologia , Sarampo/complicações , Sarampo/epidemiologia , Progressão da Doença , Inquéritos e Questionários
11.
Allergol Int ; 2023 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-37981502

RESUMO

BACKGROUND: Allergen immunotherapy (AIT) is the only disease-modifying treatment for immunoglobulin (Ig) E-mediated allergy. Owing to the high prevalence and early onset of hay fever and pollen-food allergy syndrome (PFAS), a safer and simpler treatment method than conventional AIT is needed. To develop a local nasal immunotherapy using an ointment containing hypoallergenic pollen and assess its efficacy in mice and healthy humans. METHODS: Hypoallergenicity was achieved by combining pollen and galactomannan through the Maillard reaction to create birch pollen-galactomannan conjugate (BP-GMC). The binding of galactomannan to Bet v 1 was confirmed using electrophoresis and Western blotting (WB). Binding of specific IgE antibodies to BP-GMC was verified using enzyme-linked immunosorbent assay (ELISA) and basophil activation test (BAT). The localization of BP-GMC absorption was confirmed using a BALB/c mouse model. BP-GMC mixed with white petrolatum was intranasally administered to 10 healthy individuals (active drugs, 8; placebo, 2) for 14 days. RESULTS: In electrophoresis and WB, no 17-kDa band was observed. In ELISA and BAT, BP-GMC did not react to specific IgE but was bound to IgA and IgG. In the mouse model, BP-GMC was detected in nasopharyngeal-associated lymphoid tissues. In the active drug group, the salivary-specific IgA level significantly increased on day 15 (p = 0.0299), while the serum-specific IgG level significantly increased on day 85 (p = 0.0006). CONCLUSIONS: The BP-GMC ointment rapidly produced antagonistic antibodies against IgE; it is safe and easy to use and might serve as a therapeutic antigen for hay fever and PFAS.

12.
Front Immunol ; 14: 1272221, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37868957

RESUMO

Toxoplasma gondii establishes chronic infection by forming tissue cysts, and this chronic infection is one of the most common parasitic infections in humans. Our recent studies revealed that whereas CD8+ T cells of genetically resistant BALB/c mice have the capability to remove the tissue cysts of the parasite through their perforin-mediated activities, small portions of the cysts are capable of persisting in the presence of the anti-cyst CD8+ T cells. It is currently unknown how those small portions of the cysts resist or escape the T-cell immunity and persist in the hosts. In the present study, we discovered that the cysts, which persisted in the presence of the perforin-mediated CD8+ T-cell immunity, have significantly greater mRNA levels for four dense granule proteins, GRA1, GRA2, GRA3, and GRA7, and one rhoptry protein, ROP35, than the total population of the cysts present in the absence of the T cells. In addition, increased levels of mRNA for GRA1, GRA3, and ROP35 in the cysts significantly correlated with their successful persistence through the condition in which greater degrees of reduction of the cyst burden occurred through anti-cyst CD8+ T cells. In addition, GRA3-deficient T. gondii displayed significantly enhanced elimination of the cysts by anti-cyst CD8+ T cells when compared to the wild-type parasite. These results indicate that GRA3 is a key molecule that mediates in the capability of T. gondii cysts to persist by resisting or evading the anti-cyst activity of CD8+ T cells during the later stage of infection.


Assuntos
Parasitos , Toxoplasma , Humanos , Animais , Camundongos , Linfócitos T CD8-Positivos , Proteínas de Protozoários/genética , Perforina , Infecção Persistente , RNA Mensageiro
13.
Emerg Microbes Infect ; 12(2): 2278898, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37906509

RESUMO

Tick-borne encephalitis (TBE) is an infection of the central nervous system caused by the tick-borne encephalitis virus (TBEV). TBE is endemic in parts of Europe and Asia. TBEV is transmitted to humans primarily by Ixodes ticks. There have been 5 TBE cases identified in Japan, all on the northern island of Hokkaido. Rodents with TBEV antibodies and Ixodes ticks have been identified throughout Japan, indicating that TBEV infection might be undiagnosed in Japan. Residual serum and cerebrospinal fluid (CSF) collected in 2010-2021 from 520 patients ≥1 year-of-age previously hospitalized with encephalitis or meningitis of unknown etiology at 15 hospitals (including 13 hospitals outside of Hokkaido) were screened by ELISA for TBEV IgG and IgM antibodies; TBEV infection was confirmed by the gold standard neutralization test. Residual serum was available from 331 (63.6%) patients and CSF from 430 (82.6%) patients; both serum and CSF were available from 189 (36.3%). Two patients were TBE cases: a female aged 61 years hospitalized for 104 days in Oita (2000 km south of Hokkaido) and a male aged 24 years hospitalized for 11 days in Tokyo (1200 km south of Hokkaido). Retrospective testing also identified a previous TBEV infection in a female aged 45 years hospitalized for 12 days in Okayama (1700 km south of Hokkaido). TBEV infection should be considered as a potential cause of encephalitis or meningitis in Japan. TBE cases are likely undiagnosed in Japan, including outside of Hokkaido, due to limited clinical awareness and lack of availability of TBE diagnostic tests.


Assuntos
Vírus da Encefalite Transmitidos por Carrapatos , Encefalite Transmitida por Carrapatos , Ixodes , Meningite , Animais , Humanos , Masculino , Feminino , Encefalite Transmitida por Carrapatos/diagnóstico , Encefalite Transmitida por Carrapatos/epidemiologia , Japão/epidemiologia , Estudos Retrospectivos
14.
Tohoku J Exp Med ; 261(3): 239-247, 2023 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-37704418

RESUMO

Vasohibin-2 (VASH2), a homologue of vasohibin-1 (VASH1), is overexpressed in various cancer cells and promotes tumor progression. We therefore regard VASH2 as a molecular target for cancer treatment. Here we applied vaccine technology to develop a therapy against VASH2. We selected two amino acid sequences of VASH2 protein; the MTG and RRR peptides, which contain possible B cell epitopes. These sequences are identical between the human and murine VASH2 proteins and distinct from those of the VASH1 protein. We conjugated these peptides with the carrier protein keyhole limpet hemocyanin, mixed with an adjuvant, and injected subcutaneously twice at a 2-week interval in mice. Both vaccines increased antibodies against the antigen peptide; however, only the MTG peptide vaccine increased antibodies that recognized the recombinant VASH2 protein. When Lewis lung cancer (LLC) cells were subcutaneously inoculated, tumors isolated from mice immunized with the MTG peptide vaccine showed a significant decrease in the expression of epithelial-to-mesenchymal transition (EMT) markers. EMT is responsible for cancer cell invasion and metastasis. When the LLC cells were injected into the tail vein, the MTG peptide vaccine inhibited lung metastasis. Moreover, the MTG peptide vaccine inhibited the metastasis of pancreatic cancer cells to the liver in an orthotopic mouse model, and there was a significant inverse correlation between the ELISA titer and metastasis inhibition. Therefore, we propose that the MTG peptide vaccine is a novel anti-metastatic cancer treatment that targets VASH2 and can be applied even in the most malignant and highly metastatic pancreatic cancer.


Assuntos
Neoplasias Pancreáticas , Humanos , Animais , Camundongos , Linhagem Celular Tumoral , Anticorpos , Fatores de Transcrição , Peptídeos , Vacinas de Subunidades , Proteínas de Ciclo Celular , Proteínas Angiogênicas/metabolismo
15.
Thorac Cancer ; 14(30): 2987-2992, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37658844

RESUMO

BACKGROUND: Lung adenocarcinomas with micropapillary pattern (MP) or solid pattern (SP) have poor prognosis with frequent postoperative recurrence. However, treatment strategies for these histological subtypes have not been established. This study examined the recurrence rates and patterns in patients with these histological subtypes. METHODS: Overall, 238 patients with lung adenocarcinoma who underwent radical resection were included. According to the histological subtypes, the patients were classified into three groups: neither MP nor SP (MP-/SP-), MP (MP+), and SP (SP+). The clinical and pathological characteristics and recurrence-free survival (RFS) were examined in each group. In addition, univariate and multivariate analyses were performed to investigate the recurrence factors. The site of recurrence, PD-L1 expression, and driver mutations were examined in patients with postoperative recurrence. RESULTS: The recurrence rates were significantly higher in the MP+ and SP+ groups (p = 0.01). The RFS was significantly shorter in the MP+ and SP+ groups (p < 0.001) than in the MP-/SP- group, especially in pStage 1A (p = 0.001). The relationship between recurrence and pathologic factors was significant for pleural, lymphatic, and vascular invasion, as well as MP in univariate analysis and only for MP in multivariate analysis. Most recurrences were distant metastases in the MP+ and SP+ groups. PD-L1 was highly expressed in recurrent SP+ cases. CONCLUSIONS: Early-stage lung adenocarcinoma with MP or SP frequently has postoperative recurrence. Prevention of distant metastases is important in these patients to improve prognosis, and aggressive postoperative chemotherapy may be considered.


Assuntos
Adenocarcinoma de Pulmão , Adenocarcinoma , Neoplasias Pulmonares , Humanos , Antígeno B7-H1 , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/cirurgia , Adenocarcinoma/genética , Adenocarcinoma/cirurgia , Estadiamento de Neoplasias , Recidiva Local de Neoplasia/patologia , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/cirurgia , Prognóstico , Estudos Retrospectivos
16.
Clin Exp Immunol ; 214(2): 209-218, 2023 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-37549240

RESUMO

Peritonitis and the resulting peritoneal injuries are common problems that prevent long-term peritoneal dialysis (PD) therapy in patients with end-stage kidney diseases. Previously, we have analyzed the relationship between the complement system and progression of peritoneal injuries associated with PD, particularly focusing on the early activation pathways and effects of the anaphylatoxins. We here utilized a novel mAb 2H2 that blocks assembly of the membrane attack complex (MAC) to investigate roles of the complement terminal pathway in PD-associated peritoneal injury. We intraperitoneally injected mAb 2H2 anti-C5b-7 (2.5 or 5 mg/rat) once or twice over the five-day course of the experiment to investigate the effects of inhibiting formation of MAC in a fungal rat peritonitis model caused by repeated intraperitoneal administration of zymosan after methylglyoxal pretreatment (Zy/MGO model). Rats were sacrificed on day 5 and macroscopic changes in both parietal and visceral peritoneum evaluated. Peritoneal thickness, the abundance of fibrinogen and complement C3 and MAC deposition in tissue and accumulation of inflammatory cells were pathologically assessed. The results showed that mAb 2H2, but not isotype control mAb, reduced peritoneal thickness and accumulation of inflammatory cells in a dose and frequency-dependent manner in the Zy/MGO model. These effects were accompanied by decreased C3, MAC, and fibrinogen deposition in peritoneum. In conclusion, in the rat Zy/MGO model, complement terminal pathway activation and MAC formation substantially contributed to development of peritoneal injuries, suggesting that MAC-targeted therapies might be effective in preventing development of peritoneal injuries in humans.


Assuntos
Peritônio , Peritonite , Humanos , Ratos , Animais , Peritônio/lesões , Peritônio/metabolismo , Óxido de Magnésio/metabolismo , Óxido de Magnésio/farmacologia , Ratos Sprague-Dawley , Peritonite/tratamento farmacológico , Ativação do Complemento , Complexo de Ataque à Membrana do Sistema Complemento/metabolismo , Fibrinogênio/metabolismo
17.
Rinsho Ketsueki ; 64(7): 608-613, 2023.
Artigo em Japonês | MEDLINE | ID: mdl-37544719

RESUMO

A 69-year-old male patient was referred to our hospital for further examination of hypoglycemia, splenomegaly, and para-aortic lymphadenopathy. The patient was diagnosed with diffuse large B-cell lymphoma (DLBCL) by para-aortic lymph node biopsy. Hypoglycemia was refractory to glucose supplementation but improved shortly after chemotherapy. This situation suggested that hypoglycemia was caused by lymphoma. We compared the expression levels of glyceraldehyde 3-phosphate dehydrogenase, a glycolytic enzyme whose expression is positively correlated with the glycolytic activity of cells, between the current case and two cases of DLBCL without hypoglycemia to explore the possibility that hypoglycemia was due to intense glucose consumption by lymphoma cells through their high glycolytic activity. Results revealed substantially higher expression levels of glyceraldehyde 3-phosphate dehydrogenase in the current case than in DLBCL without hypoglycemia, suggesting that the glycolytic pathway was enhanced in the current case. These results implied that intense glucose consumption by lymphoma cells through their high glycolytic activity causes hypoglycemia.


Assuntos
Hipoglicemia , Linfoma Difuso de Grandes Células B , Idoso , Humanos , Masculino , Glucose/metabolismo , Glucose/uso terapêutico , Gliceraldeído-3-Fosfato Desidrogenases/metabolismo , Hipoglicemia/etiologia , Linfoma Difuso de Grandes Células B/complicações , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/diagnóstico
18.
Microbes Infect ; 25(8): 105182, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37423326

RESUMO

CD8+ T cells from HLA-A2.1-transgenic mice, but not wild-type mice, immunized with the amino-terminus region (aa 41-152) of dense granule protein 6 (GRA6Nt) of Toxoplasma gondii secreted large amounts of perforin and granzyme B in response to GRA6Nt through antigen presentation by HLA-A2.1 in vitro. When those CD8+ T cells were transferred into chronically infected HLA-A2.1-expressing NSG mice deficient in T cells, cerebral cyst burden of the recipients of HLA-A2.1-transgenic T cells, but not of WT T cells, became significantly less than that of control mice with no cell transfer. Furthermore, the significant reduction of the cyst burden by a transfer of the HLA-A2.1-transgenic CD8+ immune T cells required an expression of HLA-A2.1 in the recipient NSG mice. Thus, antigen presentation of GRA6Nt by human HLA-A2.1is able to activate anti-cyst CD8+ T cells that eliminate T. gondii cysts through antigen presentation by human HLA-A2.1.


Assuntos
Parasitos , Toxoplasma , Humanos , Camundongos , Animais , Toxoplasma/genética , Linfócitos T CD8-Positivos , Linfócitos T Citotóxicos , Antígeno HLA-A2/genética , Antígeno HLA-A2/metabolismo , Apresentação de Antígeno , Imunização , Camundongos Transgênicos
19.
Radiol Case Rep ; 18(9): 3076-3079, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37434615

RESUMO

Extracranial metastases from intracranial meningioma involve multiple organs with repeatedly recurrence. Due to the rarity of these metastases, management remains to be established, especially in cases that are not amenable to surgery, such as postsurgical relapse and multiple metastases. We present the case of a right tentorial meningioma with multiple extracranial metastases, including postsurgical recurrent liver metastases. The intracranial meningioma was surgically resected when the patient was 53 years of age. The patient was 66 years of age when the hepatic lesion was first revealed, for which an extended right posterior sectionectomy was performed. Histopathology demonstrated a metastatic meningioma. Twelve months after liver resection, multiple local recurrences in the right hepatic lobe were revealed. Because additional surgical resection would put the patient at risk of declining residual liver function, we performed selective transarterial chemoembolization, resulting in a reduction in size and good control without relapse. Selective transarterial chemoembolization for incurable liver metastatic meningiomas could be valuable in palliating patients unsuitable for surgery.

20.
Commun Chem ; 6(1): 159, 2023 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-37524908

RESUMO

Chemical functionalisation of semiconducting single-walled carbon nanotubes (SWNTs) can tune their local band gaps to induce near-infrared (NIR) photoluminescence (PL). However, tuning the PL to telecommunication wavelengths (>1300 nm) remains challenging. The selective emergence of NIR PL at the longest emission wavelength of 1320 nm was successfully achieved in (6,5) SWNTs via cyclic perfluoroalkylation. Chiral separation of the functionalised SWNTs showed that this functionalisation was also effective in SWNTs with five different chiral angles. The local band gap modulation mechanism was also studied using density functional theory calculations, which suggested the effects of the addenda and addition positions on the emergence of the longest-wavelength PL. These findings increase our understanding of the functionalised SWNT structure and methods for controlling the local band gap, which will contribute to the development and application of NIR light-emitting materials with widely extended emission and excitation wavelengths.

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