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1.
Kyobu Geka ; 77(5): 389-393, 2024 May.
Artigo em Japonês | MEDLINE | ID: mdl-38720609

RESUMO

Primary pulmonary diffuse large B-cell lymphoma( DLBCL) is rare, accounting for 0.4% to 1.0% of all malignant lymphomas and 0.45% of all lung malignancies. We report a case of primary pulmonary DLBCL caused by methotrexate-associated lymphoproliferative disorder (MTX-LPD). A 73-year-old man was referred to our hospital due to a growing lung nodule. Transbronchoscopic biopsy did not confirm the diagnosis, but positron emission tomography-computed tomography (PET-CT) showed an accumulation of SUVmax 28.7 in the same area and SUVmax 40.5 in the contralateral mediastinum, suggesting an advanced primary lung cancer. A partial thoracoscopic left lower lobe resection was performed in our department. Histopathological examination revealed AE1/AE3 negative, CD20 and 79a positive, bcl-2 positive, and a diagnosis of primary lung DLBCL. MTX-LPD was suspected, and discontinuation of the drug resulted in subsequent shrinkage of the residual tumor. If the diagnosis cannot be made by transbronchoscopic biopsy of an expanding nodule shadow, aggressive surgical diagnosis should be considered.


Assuntos
Neoplasias Pulmonares , Linfoma Difuso de Grandes Células B , Humanos , Masculino , Idoso , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/cirurgia , Neoplasias Pulmonares/patologia , Linfoma Difuso de Grandes Células B/patologia , Linfoma Difuso de Grandes Células B/diagnóstico por imagem , Linfoma Difuso de Grandes Células B/cirurgia , Diagnóstico Diferencial , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada
2.
Kyobu Geka ; 77(1): 68-71, 2024 Jan.
Artigo em Japonês | MEDLINE | ID: mdl-38459848

RESUMO

Double aortic arch is an embryological abnormality of the aortic arch forming a vascular ring. It has been noted that the right recurrent nerve travels differently in patients with a duplicated aortic arch and may be in close proximity to the area of superior mediastinal lymph node dissection in lung cancer. We report a surgical case of a patient with right middle lung cancer associated with a duplicated aortic arch. A 64-year-old man was referred to our hospital because of a nodular shadow in the right lung field noted on chest X-ray during a medical checkup. A transbronchial needle biopsy revealed a diagnosis of adenocarcinoma, and right middle lobe resection and lymph node dissection were performed. When dissecting the superior mediastinal lymph nodes in a patient with an overlapping aortic arch, it was necessary to carefully perform the operation, paying attention to the running of the right recurrent nerve.


Assuntos
Neoplasias Pulmonares , Anel Vascular , Masculino , Humanos , Pessoa de Meia-Idade , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/cirurgia , Anel Vascular/patologia , Anel Vascular/cirurgia , Pulmão/patologia , Mediastino , Excisão de Linfonodo
3.
Neurotrauma Rep ; 5(1): 128-138, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38414780

RESUMO

Although many interventions for acute spinal cord injury (SCI) appear promising in experimental models, translation directly from experimental animals to human patients is a large step that can be problematic. Acute SCI occurs frequently in companion dogs and may provide a model to ease translation. Recently, incision of the dura has been highlighted in both research animals and human patients as a means of reducing intraspinal pressure, with a view to improving perfusion of the injured tissue and enhancing functional recovery. Observational clinical data in humans and dogs support the notion that it may also improve functional outcome. Here, we report the results of a multi-center randomized controlled trial of durotomy as an adjunct to traditional decompressive surgery for treatment of severe thoracolumbar SCI caused by acute intervertebral disc herniation in dogs. Sample-size calculation was based on the proportion of dogs recovering ambulation improving from an expected 55% in the traditional surgery group to 70% in the durotomy group. Over a 3.5-year period, we enrolled 140 dogs, of which 128 had appropriate duration of follow-up. Overall, 65 (51%) dogs recovered ambulation. Recovery in the traditional decompression group was 35 of 62 (56%) dogs, and in the durotomy group 30 of 66 (45%) dogs, associated with an odds ratio of 0.643 (95% confidence interval: 0.320-1.292) and z-score of -1.24. This z-score indicates trial futility to reach the target 15% improvement over traditional surgery, and the trial was terminated at this stage. We conclude that durotomy is ineffective in improving functional outcome for severe acute thoracolumbar SCI in dogs. In the future, these data can be compared with similar data from clinical trials on duraplasty in human patients and will aid in determining the predictive validity of the "companion dog model" of acute SCI.

4.
J Stroke Cerebrovasc Dis ; 32(7): 107150, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37119792

RESUMO

OBJECTIVE: To examine changes in drugs for subacute stroke patients and elucidate the impact of medications on rehabilitation outcomes. MATERIALS AND METHODS: A total of 295 subacute stroke patients who were admitted to the convalescent rehabilitation ward between June 2018 and May 2019 were included. Polypharmacy was defined as five or more drugs at admission. The primary outcome was the Functional Independence Measure Total score (FIM-T) at discharge. Multiple regression analysis was performed to examine the relationships between the FIM-T at discharge and drug changes or other factors. This study was conducted in two stages. The first analysis included all stroke patients, and the second analysis included only stroke patients with polypharmacy. RESULTS: On multiple regression analysis, the number of drugs at admission (ß=-0.628) was associated with FIM-T at discharge of all stroke patients. Furthermore, the number of additional drugs during hospitalization (ß=-1.964) was associated with FIM-T at discharge in the 176 stroke patients with polypharmacy. CONCLUSION: This study suggested that the number of drugs at admission and the addition of drugs during hospitalization might have a negative impact on the rehabilitation outcomes of subacute stroke patients.


Assuntos
Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral , Humanos , Recuperação de Função Fisiológica , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/complicações , Hospitalização , Atividades Cotidianas , Resultado do Tratamento , Estudos Retrospectivos
5.
Parasitol Int ; 95: 102742, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36870444

RESUMO

Parasitic helminths modify host immune reactions to promote long-term parasitism. We previously purified a glycoprotein, plerocercoid-immunosuppressive factor (P-ISF), from the excretory/secretory products of Spirometra erinaceieuropaei plerocercoids and reported its cDNA and genomic DNA sequences. In this study, we isolated extracellular vesicles (EVs) from the excretory/secretory products of S. erinaceieuropaei plerocercoids and found that they suppressed the production of nitric oxide and the gene expression of tumor necrosis factor-α, interleukin-1ß, and interleukin-6 in lipopolysaccharide-stimulated macrophages. EVs are membrane-bound vesicles 50-250 nm in diameter and are localized in the whole bodies of plerocercoids. EVs from plerocercoids encapsulate a variety of unidentified proteins and microRNAs (miRNAs), which are non-coding RNAs that play essential roles in post-transcriptional gene regulation. The miRNAs of the EVs were analyzed, and 334,137 sequencing reads were mapped to the genomes of other organisms. A total of 26 different miRNA families were identified, including miR-71, miR-10-5p, miR-223, and let-7-5p, which have been reported to have immunosuppressive effects. We confirmed that P-ISF was present in the supernatant but not in the EVs by western blotting with an anti-P-ISF antibody. These results suggest that S. erinaceieuropaei plerocercoids suppress host immunity by releasing P-ISF and EVs.


Assuntos
Vesículas Extracelulares , MicroRNAs , Spirometra , Humanos , Animais , Camundongos , Spirometra/genética , Macrófagos , Glicoproteínas , MicroRNAs/genética , MicroRNAs/metabolismo
6.
Biomolecules ; 13(3)2023 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-36979393

RESUMO

Plasmodium malaria parasites use erythrocyte-binding-like (EBL) ligands to invade erythrocytes in their vertebrate host. EBLs are released from micronemes, which are secretory organelles located at the merozoite apical end and bind to erythrocyte surface receptors. Because of their essential nature, EBLs have been studied as vaccine candidates, such as the Plasmodium vivax Duffy binding protein. Previously, we showed through using the rodent malaria parasite Plasmodium yoelii that a single amino acid substitution within the EBL C-terminal Cys-rich domain (region 6) caused mislocalization of this molecule and resulted in alteration of the infection course and virulence between the non-lethal 17X and lethal 17XL strains. In the present study, we generated a panel of transgenic P. yoelii lines in which seven of the eight conserved Cys residues in EBL region 6 were independently substituted to Ala residues to observe the consequence of these substitutions with respect to EBL localization, the infection course, and virulence. Five out of seven transgenic lines showed EBL mislocalizations and higher parasitemias. Among them, three showed increased virulence, whereas the other two did not kill the infected mice. The remaining two transgenic lines showed low parasitemias similar to their parental 17X strain, and their EBL localizations did not change. The results indicate the importance of Cys residues in EBL region 6 for EBL localization, parasite infection course, and virulence and suggest an association between EBL localization and the parasite infection course.


Assuntos
Malária , Plasmodium yoelii , Animais , Camundongos , Ligantes , Cisteína/metabolismo , Plasmodium yoelii/genética , Plasmodium yoelii/metabolismo , Parasitemia , Sequência de Aminoácidos , Proteínas de Protozoários/metabolismo , Moléculas de Adesão Celular/metabolismo , Malária/metabolismo , Eritrócitos/metabolismo
7.
Kyobu Geka ; 76(2): 148-151, 2023 Feb.
Artigo em Japonês | MEDLINE | ID: mdl-36731851

RESUMO

Osteopetrosis is a heterogeneous group of heritable conditions. It varies greatly in severity, and fracture treatment remains a matter of controversy due to altered responses to fixation and the risk of osteomyelitis. Therefore, sternotomy outcomes in this condition are unclear. We report the case of a patient with osteopetrosis and coronary artery disease (CAD). A 78-year-old man with osteopetrosis presented with frequent chest pain. Coronary angiography revealed two-vessel CAD. Percutaneous coronary intervention was contraindication because of coronary aneurysm in the left main trunk. Considering risks in median sternotomy, we performed minimally invasive cardiac surgery through left minithoracotomy for coronary artery bypass grafting( CABG). But we needed to break the left fourth rib to obtain sufficient surgical views. To the best of our knowledge, this is the first case report on CABG for a patient with osteopetrosis and endoscopic surgery without rib retractor is recommended.


Assuntos
Doença da Artéria Coronariana , Osteopetrose , Masculino , Humanos , Idoso , Osteopetrose/complicações , Osteopetrose/diagnóstico por imagem , Osteopetrose/cirurgia , Resultado do Tratamento , Doença da Artéria Coronariana/cirurgia , Ponte de Artéria Coronária , Angiografia Coronária , Procedimentos Cirúrgicos Minimamente Invasivos
8.
Surg Today ; 53(7): 816-823, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36441399

RESUMO

PURPOSE: Cholinesterase is a nutritional marker associated with sarcopenia. The present study evaluated the relationship between cholinesterase and postoperative infectious complications in patients undergoing colorectal resection for colorectal cancer. METHODS: The study involved 231 patients who had undergone colorectal resection for colorectal cancer. We retrospectively investigated the relationship between preoperative serum cholinesterase levels and postoperative infectious complications. Univariate and multivariate analyses were performed to identify independent risk factors for postoperative infectious complications. We then performed stratified analyses to assess the interaction between cholinesterase and clinical variables to predict postoperative infectious complications. RESULTS: In the multivariate analysis, the body mass index (P = 0.010), serum cholinesterase levels (P = 0.005), sarcopenia (P = 0.003) and blood loss (P < 0.001) were independent risk factors for postoperative infectious complications. In stratified analyses, the association between serum cholinesterase levels and postoperative infectious complications differed by the sarcopenia status (Pinteraction = 0.006). CONCLUSION: Preoperative serum cholinesterase levels may be useful for predicting postoperative infectious complications in colorectal cancer surgery. The association differs by the sarcopenia status, suggesting a potential interaction between nutritional markers and sarcopenia.


Assuntos
Colinesterases , Neoplasias Colorretais , Doenças Transmissíveis , Sarcopenia , Humanos , Neoplasias Colorretais/cirurgia , Neoplasias Colorretais/complicações , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Fatores de Risco , Sarcopenia/complicações , Colinesterases/sangue
9.
Mol Cancer Ther ; 22(1): 12-24, 2023 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-36279567

RESUMO

Innate and adaptive resistance to cancer therapies, such as chemotherapies, molecularly targeted therapies, and immune-modulating therapies, is a major issue in clinical practice. Subpopulations of tumor cells expressing the receptor tyrosine kinase AXL become enriched after treatment with antimitotic drugs, causing tumor relapse. Elevated AXL expression is closely associated with drug resistance in clinical samples, suggesting that AXL plays a pivotal role in drug resistance. Although several molecules with AXL inhibitory activity have been developed, none have sufficient activity and selectivity to be clinically effective when administered in combination with a cancer therapy. Here, we report a novel small molecule, ER-851, which is a potent and highly selective AXL inhibitor. To investigate resistance mechanisms and identify driving molecules, we conducted a comprehensive gene expression analysis of chemoresistant tumor cells in mouse xenograft models of genetically engineered human lung cancer and human triple-negative breast cancer. Consistent with the effect of AXL knockdown, cotreatment of ER-851 and antimitotic drugs produced an antitumor effect and prolonged relapse-free survival in the mouse xenograft model of human triple-negative breast cancer. Importantly, when orally administered to BALB/c mice, this compound did not induce retinal toxicity, a known side effect of chronic MER inhibition. Together, these data strongly suggest that AXL is a therapeutic target for overcoming drug resistance and that ER-851 is a promising candidate therapeutic agent for use against AXL-expressing antimitotic-resistant tumors.


Assuntos
Antimitóticos , Neoplasias de Mama Triplo Negativas , Humanos , Animais , Camundongos , Receptor Tirosina Quinase Axl , Antimitóticos/farmacologia , Proteínas Proto-Oncogênicas/metabolismo , Resistencia a Medicamentos Antineoplásicos , Linhagem Celular Tumoral , Inibidores de Proteínas Quinases/farmacologia , Ensaios Antitumorais Modelo de Xenoenxerto
10.
Chem Biol Drug Des ; 101(3): 727-739, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36334047

RESUMO

The identification of biologically active target compounds and their binding proteins is important in mechanism-of-action studies for drug development. Additionally, the newly discovered binding proteins provide unforeseen ideas for novel drug discovery and for subsequent structural transformation to improve target specificity. Based on the lead and final candidate compounds related to the type 5 phosphodiesterase (PDE5) inhibitor E4021, we designed chemical probes and identified their target proteins by the affinity chromatography approach. Aldehyde dehydrogenase family 1 member A3 (ALDH1A3), currently reported as a cancer stem cell target, was clearly isolated as a binding protein of the lead 'immature' inhibitor probe against PDE5. In the early derivatization to the closely related structure, Compound 5 (ER-001135935) was found to significantly inhibit ALDH1A3 activity. The discovery process of a novel ALDH1A3-selective inhibitor with affinity-based binder identification is described, and the impact of this identification method on novel drug discovery is discussed.


Assuntos
Aldeído Oxirredutases , Inibidores de Fosfodiesterase , Aldeído Oxirredutases/metabolismo , Células-Tronco Neoplásicas/metabolismo , Descoberta de Drogas
11.
Surg Today ; 53(4): 513-521, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36255498

RESUMO

PURPOSE: The liver function in outflow-obstructed regions is reportedly impaired; however, the functional decrease has not been quantitatively assessed. We therefore evaluated the uptake of indocyanine green (ICG) into hepatocytes and the mRNA expression associated with the liver function in outflow-obstructed regions using rat models. METHODS: A total of 20 rats with the ligation of the right median hepatic vein to induce outflow obstruction were studied. Five rats each were grouped by the time of re-laparotomy, and the fluorescence intensity (FI) values of ICG. The mRNA expression, including that of Albumin, Cytochrome P450 (Cyp) 1a2, Cyp3a1, Cyp7a1, and Gamma-glutamylcysteine synthetase, in outflow-obstructed (mRNAOut-Ob) and non-outflow-obstructed (mRNANon) regions was assessed. RESULTS: Microscopic fluorescence imaging showed that the FI values were significantly lower in outflow-obstructed regions than in non-outflow-obstructed regions at 12 h, 24 h, and 3 days after ligation of the hepatic vein. The mRNAOut-Ob/mRNANon ratios decreased to approximately 30% at 12 h after the outflow obstruction and increased to approximately 70-80% at 7 days. CONCLUSIONS: The liver function in outflow-obstructed regions was impaired in terms of the uptake of ICG and the mRNA expression. Our findings may help estimate the postoperative functional remnant liver volume by considering the decrease in the liver function in outflow-obstructed regions.


Assuntos
Veias Hepáticas , Fígado , Ratos , Animais , Fígado/irrigação sanguínea , Veias Hepáticas/cirurgia , Hepatócitos , Verde de Indocianina/metabolismo , Imagem Óptica/métodos , RNA Mensageiro/metabolismo
12.
Minerva Cardiol Angiol ; 71(3): 294-302, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35837831

RESUMO

BACKGROUND: Although drug-coated balloon (DCB)-based stent-less percutaneous coronary intervention (PCI) for de-novo lesions has attracted more attention, outcomes of the DCB procedure for hemodialysis (HD) patients are reported to be inferior to those for non-HD patients, similarly to drug-eluting stent (DES). Recent several reports have shown that rotational atherectomy (RA) followed by DCB treatment (RA/DCB) could be an option of revascularization strategy particularly for calcified de-novo lesions even in the new-generation DES era; however, efficacy of the RA/DCB procedure for HD patients remains unclear. METHODS: A total of 47 consecutive cases (53 lesions) undergoing RA/DCB for de-novo lesions were enrolled. According to the presence/absence of HD at baseline, the 47 cases were divided into the HD cases (N.=16) and the non-HD cases (N.=31), and the 53 lesions were divided into the HD lesions (N.=20) and the non-HD lesions (N.=33). RESULTS: The HD cases had a significantly lower prevalence of dyslipidemia and smoking than the non-HD cases. Final RA burr size, DCB diameter used, and angiographic success rate of PCI did not significantly differ between the 2 groups. Preprocedural, post-procedural, and follow-up QCA parameters were also similar between the 2 groups. Twelve-month clinical outcomes were comparable between the 2 groups. CONCLUSIONS: Mid-term outcomes of stent-less PCI using RA/DCB for de-novo lesions in HD patients might be comparable to those in non-HD patients, suggesting efficacy of pretreatment of RA prior to DCB treatment in HD patients.


Assuntos
Angioplastia Coronária com Balão , Aterectomia Coronária , Doença da Artéria Coronariana , Stents Farmacológicos , Intervenção Coronária Percutânea , Humanos , Aterectomia Coronária/efeitos adversos , Aterectomia Coronária/métodos , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/cirurgia , Intervenção Coronária Percutânea/efeitos adversos , Angioplastia Coronária com Balão/efeitos adversos , Angioplastia Coronária com Balão/métodos , Stents Farmacológicos/efeitos adversos , Resultado do Tratamento , Angiografia Coronária/métodos , Stents , Diálise Renal
13.
J Vet Med Sci ; 85(1): 62-70, 2023 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-36418080

RESUMO

Idiopathic non-infectious meningoencephalomyelitis (NIME), which is thought to be an immune-mediated disease, is a common inflammatory disease in dogs. Meningoencephalomyelitis of unknown origin (MUO), a subgroup of NIME, consists of necrotizing meningoencephalitis (NME), necrotizing leukoencephalitis, and granulomatous meningoencephalomyelitis. Recent studies have shown associations between disease development and dog leukocyte antigen (DLA) class II genes in NME in Pugs and in NIME in Greyhounds. This study focused on Chihuahuas, which have a high incidence of MUO and are one of the most common dog breeds in Japan. Because the development of MUO seems to be associated with DLA class II genes, we aimed to evaluate the association between DLA class II genes and MUO development in Chihuahuas. Blood samples were obtained from 22 Chihuahuas with MUO (MUO group) and 46 without neurological diseases (control). The allele sequences of three DLA class II loci were determined, and haplotypes were estimated from these data. In total, 23 haplotypes were detected. The frequency of one haplotype (DLA-DRB1*015:01--DQA1*006:01--DQB1*023:01) was significantly higher in the MUO group than in the control group (odds ratio, 7.11; 95% confidence interval, 1.37-36.81; P=0.0141). The results suggest that the development of MUO in Chihuahuas may be associated with DLA class II genes. Because the identified risk haplotypes differed from those of other breeds, the pathogenesis of NIME-related diseases may differ among dog breeds.


Assuntos
Doenças do Cão , Leucócitos , Cães , Animais , Haplótipos , Alelos , Japão/epidemiologia , Doenças do Cão/genética
14.
Dysphagia ; 38(1): 211-219, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-35507038

RESUMO

This study evaluated the safety of laryngeal closure and post-surgical changes in swallowing function of patients with amyotrophic lateral sclerosis (ALS) and proposed an appropriate surgical strategy for patients with ALS. Clinical and surgical data of 26 consecutive patients with ALS who underwent laryngeal closure at Nagoya University Hospital in Japan between 2003 and 2020 were retrospectively analyzed. Changes in swallowing functions were evaluated before and approximately 1 month post-surgery using Neuromuscular Disease Swallowing Status Scale (NdSSS), and Functional Oral Intake Scale (FOIS). The median operation time was 126 min (range, 51-163 min), and the median intraoperative blood loss was 20 mL (range, 0-88 mL). Among the 26 ALS patients who underwent laryngeal closure, grade 1 (mild) complications occurred in three patients (12%); however, no severe complications were observed. After surgery, 25 patients (96%) maintained the swallowing function and only one patient (4%) had deteriorating NdSSS and FOIS scores. No patients were referred to our hospital due to severe aspiration pneumonia after the surgery. Two patients did not require a feeding tube after the surgery and returned to oral intake. Laryngeal closure may be a safe surgical procedure for preventing chronic aspiration and may also maintain swallowing function of patients with ALS. Further multicenter prospective studies using the gold standard videofluoroscopic swallowing examination are required to support our findings.


Assuntos
Esclerose Lateral Amiotrófica , Transtornos de Deglutição , Humanos , Esclerose Lateral Amiotrófica/complicações , Transtornos de Deglutição/diagnóstico , Estudos Prospectivos , Estudos Retrospectivos , Deglutição
15.
Neurology ; 100(1): e84-e93, 2023 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-36180235

RESUMO

BACKGROUND AND OBJECTIVES: To assess the clinical and electrophysiologic features of female carriers and early-stage male patients with spinal and bulbar muscular atrophy (SBMA) to elucidate the early pathophysiologic changes of the disease. METHODS: Female carriers, early-stage male patients with SBMA, and age-matched male and female healthy controls were recruited. The results of motor functional scales, motor unit number estimation, dual-energy X-ray absorptiometry, and peripheral blood tests were compared between female carriers and healthy female controls and between patients with SBMA and healthy male controls. EMG was also investigated in female carriers. RESULTS: We enrolled 21 female carriers and 11 early-stage male patients. Seventeen female and 14 male age-matched healthy controls were also enrolled. Female carriers experienced early-stage symptoms such as muscle cramps more frequently than healthy female controls. Decreased motor unit number estimation and EMG abnormalities including high amplitude or polyphasic potentials were observed in female carriers together with mild muscle weakness in neck flexion and a slow walking speed. Changes of muscle-related markers, including serum creatine kinase and dual-energy X-ray absorptiometry, were clearly detected in early-stage male patients with SBMA, but not in female carriers. DISCUSSION: The present study revealed that female carriers of SBMA manifest mild muscular weakness associated with changes in neurogenic biomarkers. Conversely, male patients showed neurogenic and myopathic changes even at the early stage. These results suggest a testosterone-independent neurodegenerative pathophysiology in female SBMA carriers.


Assuntos
Atrofia Bulboespinal Ligada ao X , Atrofia Muscular Espinal , Humanos , Masculino , Feminino , Atrofia Muscular Espinal/diagnóstico por imagem , Heterozigoto
16.
Gan To Kagaku Ryoho ; 50(12): 1301-1305, 2023 Dec.
Artigo em Japonês | MEDLINE | ID: mdl-38247068

RESUMO

In cancer chemotherapy, identifying factors that may affect overall survival is clinically beneficial. In this study, we examined the factors associated with overall survival in patients treated with gemcitabine plus paclitaxel(albumin suspension) (GN)for pancreatic cancer. We included 91 pancreatic cancer patients who underwent GN therapy as the first-line treatment from January 2015-November 2021. In addition to survival from the start of therapy, the factors surveyed were patient background(gender, age, BMI, etc), dose at the start of treatment, baseline laboratory values, presence or absence of neutrophil count reduction, and modified Glasgow Prognostic Score(mGPS). Multivariate analysis showed that a neutrophil count reduction of Grade 3 or higher(p=0.004)and mGPS≤1(p=0.004)significantly increased overall survival. Consequently, 54.9% of patients(50/91)showed a neutrophil count reduction of Grade 3 or higher, and 35.2% of patients (32/91)showed expression of the first course. The study suggests that neutrophil count reduction of Grade 3 or higher and mGPS≤1 are indicators of prolonged overall survival. In particular, neutrophil count reduction had a high incidence in the first course; therefore, appropriate management is required from early stages of treatment. In addition, nutritional support care should be considered prior to starting treatment.


Assuntos
Gencitabina , Neoplasias Pancreáticas , Humanos , Contagem de Leucócitos , Neoplasias Pancreáticas/tratamento farmacológico , Albuminas
17.
BMC Nephrol ; 23(1): 396, 2022 12 09.
Artigo em Inglês | MEDLINE | ID: mdl-36494791

RESUMO

BACKGROUND: Proliferative glomerulonephritis with monoclonal immunoglobulin G (IgG) deposits (PGNMID) is a rare monoclonal gammopathy of renal significance with dense deposits of monoclonal immunoglobulin. CASE PRESENTATION: We report a 78-year-old Japanese male patient with mild proteinuria and lower extremity edema. Monoclonal immunoglobulin could not be identified in his serum or urine. Although his bone marrow biopsy was negative, renal biopsy found features of membranoproliferative glomerulonephritis (MPGN) with deposition of monoclonal IgG2 kappa. Electron microscopy examination revealed non-organized electron-dense deposits in the subepithelial, and subendothelial mesangial regions. Steroid monotherapy was performed after diagnosis of PGNMID but complete remission was not achieved. CONCLUSION: PGNMID with IgG3 kappa deposits is the most common in cases with the histological feature of MPGN. There are few cases of PGNMID with IgG2 kappa deposits exhibiting MPGN. This report describes a very rare case of PGNMID with the histological feature of MPGN.


Assuntos
Glomerulonefrite Membranoproliferativa , Glomerulonefrite , Masculino , Humanos , Idoso , Imunoglobulina G , Glomerulonefrite Membranoproliferativa/patologia , Glomerulonefrite/diagnóstico , Glomerulonefrite/tratamento farmacológico , Glomerulonefrite/patologia , Rim/patologia , Anticorpos Monoclonais
18.
Cell Rep Methods ; 2(9): 100289, 2022 09 19.
Artigo em Inglês | MEDLINE | ID: mdl-36160042

RESUMO

It is known that the human cellular models of Alzheimer's disease (AD) and tauopathy can only recapitulate the very early stage of the disease. To overcome these limitations, we developed a technology to make forebrain organoids (FBOs) from feeder-free induced pluripotent stem cells (iPSC)s by regulating a FGF2 concentration and applied this method to generate FBOs from patients with familial AD (fAD FBOs). The obtained fAD FBOs recapitulated the amyloid-ß pathology and increased tau phosphorylation but not tau aggregates. To fully induce the tau pathology, FBOs were injected with adeno-associated virus (AAV)-expressing P301L mutant tau. In these Tau-P301L FBOs, tau fibrils were observed in the neuronal cell body and neurites with immunoelectron microscopy, in addition to the sarkosyl-insoluble and thioflavin S-positive phospho-tau aggregates. Collectively, this model can be used as a platform for investigating pathogenetic mechanisms and evaluation of target molecules for drug discovery for tauopathy.


Assuntos
Doença de Alzheimer , Células-Tronco Pluripotentes Induzidas , Tauopatias , Humanos , Doença de Alzheimer/genética , Dependovirus , Células-Tronco Pluripotentes Induzidas/metabolismo , Organoides/metabolismo , Prosencéfalo/metabolismo , Proteínas tau/genética , Tauopatias/genética , Técnicas de Transferência de Genes
19.
Ann Gastroenterol Surg ; 6(4): 587-593, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35847438

RESUMO

Aim: Frailty assessment in elderly patients is crucial to predict the postoperative course, considering that frailty is highly associated with postoperative complications and mortality. The aim of this study was to evaluate the value of osteopenia as a risk factor for severe postoperative complications in elderly patients who underwent emergency gastrointestinal surgery. Methods: This study comprised 103 elderly patients who underwent emergency gastrointestinal surgery. Osteopenia was diagnosed by measuring bone mineral density, which was calculated as the average pixel density in the midvertebral core at the 11th thoracic vertebra on the preoperative plain computed tomography image. We retrospectively investigated the relationship between preoperative osteopenia and severe postoperative complications (Clavien-Dindo classification ≥III). Univariate and multivariate analyses were performed to evaluate the risk factors for severe postoperative complications. Results: Twenty-three patients (22.3%) developed severe postoperative complications. The optimal cutoff value of bone mineral density for severe postoperative complications was 119.5 Hounsfield unit (HU) and 39 patients (37.9%) were diagnosed with osteopenia. The univariate analysis revealed that the American Society of Anesthesiologists Physical Status of ≥3 (P = .0084), hemoglobin levels (P = .0026), albumin levels (P < .001), sarcopenia (P = .015), and osteopenia (P < .001) were significantly associated with severe postoperative complications. The multivariate analysis showed that osteopenia (P = .014) was an independent risk factor for severe postoperative complications. Conclusion: Osteopenia may be a risk factor for severe postoperative complications in elderly patients after emergency gastrointestinal surgery.

20.
J Pharm Sci ; 111(10): 2745-2757, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35839866

RESUMO

In this study, we conducted a collaborative study on the classification between silicone oil droplets and protein particles detected using the flow imaging (FI) method toward proposing a standardized classifier/model. We compared four approaches, including a classification filter composed of particle characteristic parameters, principal component analysis, decision tree, and convolutional neural network in the performance of the developed classifier/model. Finally, the points to be considered were summarized for measurement using the FI method, and for establishing the classifier/model using machine learning to differentiate silicone oil droplets and protein particles.


Assuntos
Óleos de Silicone , Silicones , Tamanho da Partícula , Proteínas
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