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Peripheral blood stem cell transplantation (PBSCT) has made amyloid light-chain (AL) amyloidosis treatable. After PBSCT, hematological complete remission (HCR) can be achieved, leading to improved renal prognosis. The purpose of this study was to evaluate whether whole slide imaging of biopsy samples shows a post-treatment reduction in amyloid deposits in patients with AL amyloidosis. Patients were divided into three groups: Group A (n = 8), not eligible for PBSCT and treated with other therapies; Group B (n = 11), treated with PBSCT and achieved HCR; and Group C (n = 5), treated with PBSCT but did not achieve HCR. Clinical findings and amyloid deposition in glomeruli, interstitium, and blood vessels were compared before and after treatment using digital whole-slide imaging. Proteinuria and hypoalbuminemia improved more in Group B than in the other groups, and in Group B, amyloid deposition improved more in the glomeruli than in the interstitium and blood vessels. The long-term renal and survival prognosis was better in Group B than in the other groups. PBSCT can be expected to improve long-term clinical and renal histological prognosis in patients with AL amyloidosis who achieve HCR. Amyloid disappearance from renal tissue may take a long time even after clinical HCR.
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Hepatoid adenocarcinoma of the lung is a rare variant of adenocarcinoma. We describe a case of hepatoid adenocarcinoma of the lung that harbored KRAS G12C and responded favorably to sotorasib. A man in his 70s was found to have an abnormality on his chest X-ray. He underwent right middle lobectomy, and a pathological examination of the surgical specimen showed conventional invasive adenocarcinoma with highly focal hepatoid adenocarcinoma. He received chemoradiotherapy and concurrent radiation, followed by durvalumab for postoperative recurrence. After three doses of durvalumab, he reported feeling short of breath. A computed tomography scan showed emerging broad consolidation in the right lower lobe. Transbronchial lung biopsy specimens from the consolidation showed hepatoid adenocarcinoma harboring KRAS G12C mutation. Therefore, he was started on sotorasib 960 mg daily. Eight days later, a computed tomography scan showed that the area of consolidation had reduced in size. Progressive disease was detected after 42 days of treatment with sotorasib. The patient died 1 month after cessation of sotorasib and 3 months after postoperative recurrence. We have encountered what we believe to be the first case of hepatoid adenocarcinoma of the lung with KRAS G12C mutation that responded favorably to treatment with sotorasib.
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Loewi's discovery of acetylcholine (ACh) release from the frog vagus nerve and the discovery by Dale and Dudley of ACh in ox spleen led to the demonstration of chemical transmission of nerve impulses. ACh is now well-known to function as a neurotransmitter. However, advances in the techniques for ACh detection have led to its discovery in many lifeforms lacking a nervous system, including eubacteria, archaea, fungi, and plants. Notably, mRNAs encoding choline acetyltransferase and muscarinic and nicotinic ACh receptors (nAChRs) have been found in uninnervated mammalian cells, including immune cells, keratinocytes, vascular endothelial cells, cardiac myocytes, respiratory, and digestive epithelial cells. It thus appears that non-neuronal cholinergic systems are expressed in a variety of mammalian cells, and that ACh should now be recognized not only as a neurotransmitter, but also as a local regulator of non-neuronal cholinergic systems. Here, we discuss the role of non-neuronal cholinergic systems, with a focus on immune cells. A current focus of much research on non-neuronal cholinergic systems in immune cells is α7 nAChRs, as these receptors expressed on macrophages and T cells are involved in regulating inflammatory and immune responses. This makes α7 nAChRs an attractive potential therapeutic target.
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Acetilcolina , Sistema Colinérgico não Neuronal , Receptor Nicotínico de Acetilcolina alfa7 , Receptor Nicotínico de Acetilcolina alfa7/metabolismo , Animais , Humanos , Acetilcolina/metabolismo , Linfócitos T/imunologia , Linfócitos T/metabolismo , Macrófagos/metabolismo , Macrófagos/imunologiaRESUMO
This case report describes a 13-year-old female patient with adolescent idiopathic scoliosis (AIS) and flat back who experienced progressive kyphotic deformity after implant removal despite obtaining physiological alignment postoperatively. The patient underwent multiple surgeries, and a late-developing infection complicated her treatment course. Despite hard bracing to prevent kyphotic change, the kyphosis progressed to 74° within a year after implant removal, leading to a decrease in patient height and back pain. Revision surgery was eventually necessary. Possible factors for the kyphotic progression include injury to paraspinal back muscles due to multiple surgeries or insufficient bony fusion from late-developing infection. This case highlights the importance of thorough evaluation and follow-up for optimal patient outcomes after implant removal in AIS patients, particularly those with flat back.
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Immune cells such as T cells and macrophages express α7 nicotinic acetylcholine receptors (α7 nAChRs), which contribute to the regulation of immune and inflammatory responses. Earlier findings suggest α7 nAChR activation promotes the development of regulatory T cells (Tregs) in mice. Using human CD4+ T cells, we investigated the mRNA expression of the α7 subunit and the human-specific dupα7 nAChR subunit, which functions as a dominant-negative regulator of ion channel function, under resting conditions and T cell receptor (TCR)-activation. We then explored the effects of the selective α7 nAChR agonist GTS-21 on proliferation of TCR-activated T cells and Treg development. Varied levels of mRNA for both the α7 and dupα7 nAChR subunits were detected in resting human CD4+ T cells. mRNA expression of the α7 nAChR subunit was profoundly suppressed on days 4 and 7 of TCR-activation as compared to day 1, whereas mRNA expression of the dupα7 nAChR subunit remained nearly constant. GTS-21 did not alter CD4+ T cell proliferation but significantly promoted Treg development. These results suggest the potential ex vivo utility of GTS-21 for preparing Tregs for adoptive immunotherapy, even with high expression of the dupα7 subunit.
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Diabetic kidney disease (DKD) is the most common cause of chronic kidney disease (CKD), leading end-stage renal disease. Thus, DKD is one of the most important diabetic complications. Incretin-based therapeutic agents, such as glucagon-like peptide-1 (GLP-1) receptor agonizts and dipeptidyl peptidase-4 (DPP-4) inhibitors have been reported to elicit vasotropic actions, suggesting a potential for effecting reduction in DKD. Glucose-dependent insulinotropic polypeptide (GIP) is also classified as an incretin. However, the insulin action after GIP secretion is known to be drastically reduced in patients with type 2 diabetes. Therefore, GIP has been formally considered unsuitable as a treatment for type 2 diabetes in the past. This concept is changing as it has been reported that resistance to GIP can be reversed and its effect restored with improved glycemic control. The development of novel dual- or triple- receptor agonizts that can bind to the receptors, not only for GLP-1 but also to GIP and glucagon receptors, is intended to simultaneously address several metabolic pathways including protein, lipid, and carbohydrate metabolism. These led to the development of GIP receptor agonist-based drugs for type 2 diabetes. The possibility of combined GIP/GLP-1 receptor agonist was also explored. The novel dual GIP and GLP-1 receptor agonist tirzepatide has recently been launched (Mounjaro®, Lilly). We have revealed precise mechanisms of the renoprotective effect of GLP-1 receptor agonizts or DPP-4 inhibitors, while the long-term effect of tirzepatide will need to be determined and its potential effects on kidneys should be properly tested.
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Diabetes Mellitus Tipo 2 , Nefropatias Diabéticas , Inibidores da Dipeptidil Peptidase IV , Humanos , Incretinas/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Nefropatias Diabéticas/tratamento farmacológico , Receptor do Peptídeo Semelhante ao Glucagon 1/uso terapêutico , Polipeptídeo Inibidor Gástrico/uso terapêutico , Peptídeo 1 Semelhante ao Glucagon/farmacologia , Inibidores da Dipeptidil Peptidase IV/farmacologia , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Glicemia/metabolismo , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêuticoRESUMO
A 58-year-old man presented with dyspnea on exertion and diffuse ground-glass opacities with mosaicism on chest computed tomography in April 201X. A transbronchial lung biopsy revealed organizing pneumonia and lymphocytic infiltration, and steroids were administered. During steroid tapering, the shortness of breath and ground-glass opacities recurred, and a transbronchial lung re-biopsy revealed organizing pneumonia without a granuloma again. Based on the clinical history, imaging features, and amount of humidifier usage, hypersensitivity pneumonitis caused by a humidifier was suspected. The inhalation challenge test was considered positive, and the diagnosis was confirmed. There have been some reports of unidentified granuloma in patients with humidifier lungs. Therefore, this case suggests that humidifier lung should be considered as a possibility even if pathological examination does not reveal granulomas and inflammatory changes such as organizing pneumonia are the only findings.
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Alveolite Alérgica Extrínseca , Pneumonia em Organização , Pneumonia , Masculino , Humanos , Pessoa de Meia-Idade , Broncoscopia , Umidificadores , Alveolite Alérgica Extrínseca/diagnóstico , Dispneia , Pulmão/diagnóstico por imagemRESUMO
STUDY DESIGN: A prospective longitudinal magnetic resonance imaging (MRI) study. OBJECTIVE: The objective of this study was to describe the progression of intervertebral disk (IVD) degeneration in patients who underwent posterior decompression surgery for lumbar spinal canal stenosis (LSS). SUMMARY OF BACKGROUND DATA: IVD degeneration contributes to the pathogenesis of LSS; however, the long-term consequences of degenerative changes after decompression surgery remain unknown. MATERIALS AND METHODS: Of 258 consecutive patients who underwent posterior lumbar decompression surgery for LSS, 62 who underwent MRI at their 10-year follow-up were included; 17 age-matched asymptomatic volunteers were analyzed as controls. Three MRI findings representing IVD degeneration were graded on their severity: decrease in signal intensity, posterior disk protrusion (PDP), and disk space narrowing (DSN). Clinical outcome was assessed using the low back pain (LBP) score from the Japanese Orthopaedic Association scoring system. We examined the association between the progression of degenerative changes on MRI and LBP/associated factors using logistic regression adjusting for age at baseline and sex. RESULTS: The severity of IVD degeneration tended to be higher in patients with LSS than asymptomatic volunteers at both baseline and follow-up. IVD degeneration progressed in all patients during the 10-year follow-up period. Progression of decrease in signal intensity and PDP was observed at L1/2 in 73% and at L2/3 in 34%, respectively (the highest frequencies in the lumbar spine). Progression of DSN was highest at L4/5 in 42%. The rates of PDP and DSN progression during the 10-year follow-up period tended to be greater in patients with LSS than in asymptomatic volunteers. No significant difference in the proportion of LBP deterioration was evident for individuals with and without MRI findings of progression. CONCLUSIONS: Our study reveals a natural history of the long-term postoperative course of IVD degeneration after posterior decompression surgery for LSS. Compared with healthy controls, patients with LSS seemed to be predisposed to IVD degeneration. Lumbar decompression surgery may promote the progression of DSN; however, progression of IVD degeneration after lumbar decompression surgery was not associated with worsening LBP scores.
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Degeneração do Disco Intervertebral , Dor Lombar , Estenose Espinal , Humanos , Degeneração do Disco Intervertebral/diagnóstico por imagem , Degeneração do Disco Intervertebral/cirurgia , Degeneração do Disco Intervertebral/complicações , Estudos Prospectivos , Constrição Patológica/cirurgia , Imageamento por Ressonância Magnética/efeitos adversos , Estenose Espinal/diagnóstico por imagem , Estenose Espinal/cirurgia , Estenose Espinal/complicações , Dor Lombar/etiologia , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/cirurgia , Vértebras Lombares/patologia , Descompressão Cirúrgica/efeitos adversos , Descompressão Cirúrgica/métodos , Canal Medular/cirurgia , Resultado do TratamentoRESUMO
A 35-year-old woman was treated with chemotherapy for leukemia. One year later, allogeneic hematopoietic stem cell transplantation (HSCT) was performed with umbilical cord blood. After nine months, she developed a spiking fever, sore throat, arthralgia, pleural effusion, hyperferritinemia, and persistent generalized pruritic erythema. A skin biopsy showed dyskeratotic cells in the epidermis, neutrophil infiltration in the epidermis and upper dermis, and neutrophils in the parakeratotic layer. Treatment with tocilizumab was effective. Adult-onset Still's disease (AOSD)-like disease related to graft versus-host disease (GVHD) after HSCT was suspected. Abnormal immune states related to GVHD may cause AOSD-like disease with more severe skin lesions than usual.
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Dermatite Esfoliativa , Transplante de Células-Tronco Hematopoéticas , Doença de Still de Início Tardio , Adulto , Feminino , Humanos , Doença de Still de Início Tardio/complicações , Doença de Still de Início Tardio/diagnóstico , Doença de Still de Início Tardio/tratamento farmacológico , Dermatite Esfoliativa/etiologia , Dermatite Esfoliativa/patologia , Pele/patologia , Eritema/patologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversosRESUMO
In slowly progressive type 1 diabetes mellitus (SPIDDM), the pancreas shows sustained islet inflammation, pancreatitis, pancreatic acinar cell metaplasia/dysplasia (ADM), and intraepithelial neoplasia (PanIN), a precancerous lesion. The mechanisms underlying these changes remain unclear. The presence of enterovirus (EV) encoded-capsid protein 1 (VP1) and -2A protease (2Apro) and the innate immune responses of the pancreas were studied using immunohistochemistry and in situ hybridization in 12 SPIDDM and 19 non-diabetic control pancreases. VP1, 2Apro, and EV-RNA were detected in islets and the exocrine pancreas in all SPIDDM pancreases. Innate immune receptor, melanoma differentiation-associated gene 5 (MDA5), and interferon (IFN)-beta1 were intensified in the islets of SPIDDM patients with short disease duration. However, expressions of MDA5 and IFN-beta1were suppressed in those with longer disease duration. CD3+ T cell infiltration was observed in the VP1- and insulin-positive islets (insulitis) and exocrine acinar cells. CD11c+ dendritic cells (DCs) in islets were scarce in long-term SPIDDM. This study showed the consistent presence of EV, suggesting an association with inflammatory changes in the endocrine and exocrine pancreas in SPIDDM. Suppressed expressions of MDA5 and IFN-beta1, as well as decreased numbers of DCs in the host cells, may contribute to persistent EV infection and induction of ADM/PanIN lesions, which may potentially provide a scaffold for pancreatic neoplasms.
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Diabetes Mellitus Tipo 1 , Infecções por Enterovirus , Enterovirus , Ilhotas Pancreáticas , Pâncreas Exócrino , Humanos , Enterovirus/genética , Diabetes Mellitus Tipo 1/metabolismo , Pâncreas/metabolismo , Infecções por Enterovirus/metabolismo , Pâncreas Exócrino/metabolismo , Antígenos Virais/metabolismo , Ilhotas Pancreáticas/metabolismoRESUMO
BACKGROUND: Reoperation is usually associated with poor results and increased morbidity and hospital costs. However, the rates, causes, and risk factors for reoperation in patients undergoing lumbar spinal fusion surgery remain controversial. This study aimed to identify the risk factors for early reoperation after posterior lumbar interbody fusion surgery and to compare the clinical outcomes between patients who underwent reoperation and those who did not. METHODS: We investigated a multicenter medical record database of 1263 patients who underwent posterior lumbar interbody fusion surgery between 2012 and 2015. A total of 72 (5.7%) reoperations within two years after surgery were identified and were propensity-matched for age, sex, number of fusion segments, and surgeon's experience. RESULTS: We analyzed a total of 114 patients (57 who underwent reoperation (R group) and 57 who did not (C group)). The mean age was 62.6 ± 13.4 years, with 78 men and 36 women. The mean number of fused segments was 1.2 ± 0.5. Surgical site infection was the most common cause of reoperation. There were significant differences in the incidence of diabetes mellitus (p = 0.024), preoperative ambulation status (p = 0.046), and ASA grade (p < 0.001) between the C and R groups. The recovery rate of the Japanese Orthopaedic Association score was significantly lower in the R group compared to the C group (R: 50.5 ± 28.8%, C: 63.9 ± 33.7%, p = 0.024). There were significant differences in the bone fusion rate (R: 63.2%, C: 96.5%, p < 0.001) and incidence of screw loosening (R: 31.6%; C: 10.5%; p = 0.006). CONCLUSION: Diabetes mellitus, preoperative ambulation status, and ASA grade were significant risk factors for early reoperation following posterior lumbar interbody fusion surgery. The patients who underwent early reoperation had worse clinical outcomes than those who did not.
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Introduction: The efficacy of minimally invasive surgeries for thoracolumbar flexion-distraction injuries (FDIs) has been reported, but those surgeries were monosegmental fusion surgeries of two adjacent vertebrae with bone grafts or temporary fixations using percutaneous pedicle screws (PPSs) that were at least bisegmental. Our idea was to fuse the fracture itself, not to fuse the fractured vertebra with an adjacent vertebra or to stabilize the fractured vertebra by bridging rostrally/caudally adjacent intact vertebrae, specifically when the displacement is minimal. This study aimed to present the surgical techniques of reduction and temporary monosegmental fixation of neurologically intact thoracolumbar bony FDIs using multiaxial PPSs, which can minimize the surgical invasiveness and preserve all motion segments, as well as report three cases treated with this procedure. Technical Note: When the fracture extended from the vertebral body to the spinous process at the same level, screws were placed into the fractured vertebra rostrally to the fracture along the rostral endplate, and the caudally adjacent vertebra was instrumented beyond the fracture line. When the fracture extended from the vertebral body to the spinous process of the rostrally adjacent vertebra, screws were placed into the fractured vertebra caudally to the fracture line, and the rostrally adjacent vertebra was instrumented. The kyphotic deformity was reduced through ligamentotaxis by using MPPSs in the rostral vertebra as rigid joysticks to apply direct buttress leverage to the rostral endplate. Intraoperative blood loss was minimal. The correction of kyphotic deformity and its durability were acceptable, and the segmental range of motion of the two affected vertebrae from flexion to extension was maintained after implant removal. Conclusions: This surgery can act as the least-invasive option for the management of thoracolumbar bony FDIs to allow early ambulation without external bracing and to preserve all the motion segments.
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RATIONALE: Bronchial schwannomas are extremely rare among the benign tracheobronchial tumors and little are known about its epidemiology and optimal clinical management. Here, we report a case of bronchial schwannoma in a young Japanese man and clinical implications about epidemiology, symptom, diagnosis, and treatment of bronchial schwannoma. PATIENTS CONCERN: A 37-year-old man visited our department with a nodule incidentally found on his chest radiograph during a routine medical checkup. DIAGNOSIS: The tumor was diagnosed as a bronchial schwannoma after pathological evaluation. Microscopically, the tumor consisted of spindle cell proliferation characterized by an alternating highly ordered cellular Antoni A component with occasional nuclear palisading and a loose myxoid Antoni B component. Tumor cells were immunoreactive for S100 but not for smooth muscle actin or KIT. INTERVENTIONS: A video-assisted right middle and lower bilobectomy was performed. OUTCOME: He remains under observation without recurrence. LESSONS: In our review, many reports have come from Asian countries. Bronchial schwannoma can occur within a wide range of age groups and in both men and women. No difference in incidence was observed between right and left bronchial tree. Bronchial schwannoma is sometimes difficult to differentiate from malignant diseases. We should include bronchial schwannoma as one of the differential diagnoses of primary bronchial tumors.
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Neoplasias Brônquicas , Neurilemoma , Actinas , Adulto , Neoplasias Brônquicas/diagnóstico por imagem , Neoplasias Brônquicas/cirurgia , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Neurilemoma/diagnóstico , Neurilemoma/patologia , Neurilemoma/cirurgia , PneumonectomiaRESUMO
E type prostanoid 4 (EP4) receptors and their signaling pathways have been implicated in the development and malignant transformation of colorectal cancer. We herein demonstrated that the mono(ADP-ribosyl)ation of histone deacetylase (HDAC)1 and HDAC2 by poly(ADP-ribose) polymerase 14 (PARP14) may be required to induce the expression of EP4 receptors. The suppression of PARP14 activity by siRNA and/or its inhibitors reduced the mRNA expression of EP4 receptors. Thus, the expression of their proteins to approximately 50-80% in human colon cancer HCA-7 cells, however, which retained the activities of EP4 receptors to some extent. Since the expression levels of EP4 receptors are important factors for the maintenance of homeostasis, the adequate inhibition of PARP14 activity will be a good target for the prevention of colon cancer and/or as an alternative therapy for this disease. Since non-steroidal anti-inflammatory drugs (NSAIDs) are associated with a risk of heart attacks and stroke, novel PARP14 inhibitors will supersede NSAIDs without causing heart attacks and stroke, while maintaining appropriate EP4 receptor-mediated intestinal homeostasis.
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Neoplasias do Colo , Infarto do Miocárdio , Receptores de Prostaglandina E Subtipo EP4/genética , Anti-Inflamatórios não Esteroides , Linhagem Celular Tumoral , Neoplasias do Colo/genética , Neoplasias do Colo/patologia , Humanos , Poli(ADP-Ribose) Polimerases/metabolismo , Prostaglandinas , Acidente Vascular CerebralRESUMO
Parthanatos is programmed cell death mediated by poly(ADP-ribose) polymerase 1 (PARP1) after DNA damage. PARP1 acts by catalyzing the transfer of poly(ADP-ribose) (PAR) polymers to various nuclear proteins. PAR is subsequently cleaved, generating protein-free PAR polymers, which are translocated to the cytoplasm where they associate with cytoplasmic and mitochondrial proteins, altering their functions and leading to cell death. Proteomic studies revealed that several proteins involved in endocytosis bind PAR after PARP1 activation, suggesting endocytosis may be affected by the parthanatos process. Endocytosis is a mechanism for cellular uptake of membrane-impermeant nutrients. Rab5, a small G-protein, is associated with the plasma membrane and early endosomes. Once activated by binding GTP, Rab5 recruits its effectors to early endosomes and regulates their fusion. Here, we report that after DNA damage, PARP1-generated PAR binds to Rab5, suppressing its activity. As a result, Rab5 is dissociated from endosomal vesicles, inhibiting the uptake of membrane-impermeant nutrients. This PARP1-dependent inhibition of nutrient uptake leads to cell starvation and death. It thus appears that this mechanism may represent a novel parthanatos pathway.
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Parthanatos , Proteômica , Dano ao DNA , Poli(ADP-Ribose) Polimerase-1/metabolismo , Poli Adenosina Difosfato Ribose/metabolismo , PolímerosRESUMO
Poly(ADP-ribosyl)ation is a post-translational modification of proteins by transferring poly(ADP-ribose) (PAR) to acceptor proteins by the action of poly(ADP-ribose) polymerase (PARP). Two tankyrase (TNKS) isoforms, TNK1 and TNK2 (TNKS1/2), are ubiquitously expressed in mammalian cells and participate in diverse cellular functions, including wnt/ß-catenin signaling, telomere maintenance, glucose metabolism and mitosis regulation. For wnt/ß-catenin signaling, TNKS1/2 catalyze poly(ADP-ribosyl)ation of Axin, a key component of the ß-catenin degradation complex, which allows Axin's ubiquitination and subsequent degradation, thereby activating ß-catenin signaling. In the present study, we focused on the functions of TNKS1/2 in neuronal development. In primary hippocampal neurons, TNKS1/2 were detected in the soma and neurites, where they co-localized with PAR signals. Treatment with XAV939, a selective TNKS1/2 inhibitor, suppressed neurite outgrowth and synapse formation. In addition, XAV939 also suppressed norepinephrine uptake in PC12 cells, a rat pheochromocytoma cell line. These effects likely resulted from the inhibition of ß-catenin signaling through the stabilization of Axin, which suggests TNKS1/2 enhance Axin degradation by modifying its poly(ADP-ribosyl)ation, thereby stabilizing wnt/ß-catenin signaling and, in turn, promoting neurite outgrowth and synapse formation.
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Tanquirases , Animais , Proteína Axina/genética , Mamíferos/metabolismo , Crescimento Neuronal , Poli ADP Ribosilação , Poli Adenosina Difosfato Ribose/metabolismo , Ratos , Tanquirases/metabolismo , Via de Sinalização Wnt , beta Catenina/metabolismoRESUMO
The treatment strategy for an idiopathic retroperitoneal mass has not yet been established. Additionally, differentiating between benign and malignant is a challenge. Herein, we report a case in which we performed partial resection of a mass in a symptomatic patient with idiopathic retroperitoneal fibrosis that mimicked malignancy. A 44-year-old woman with an unremarkable medical history other than gallstones presented with a 1-month history of abdominal pain and repetitive vomiting. Imaging studies identified a large, retroperitoneal mass compressing the duodenum that had grown acutely over the preceding 2 weeks. The possibility that the mass was malignant could not be excluded. Considering the invasiveness and potential curability, we performed partial resection of the mass, which involved partial colonic resection with reconstruction, to allow for pathological diagnosis and intestinal obstruction treatment. The final pathological findings revealed that the mass consisted of hemorrhagic and fibrotic tissue without a tumorous component. The patient's postoperative course was unremarkable. She is alive 8 years postoperatively with no recurrence. In conclusion, a surgical approach, including biopsies, to idiopathic retroperitoneal fibrosis that mimics malignancy should be actively considered in symptomatic patients. Decisions regarding the required degree of surgical intervention call for sufficient, case-specific discussion.
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Neoplasias , Fibrose Retroperitoneal , Adulto , Biópsia , Diagnóstico Diferencial , Feminino , Humanos , Neoplasias/patologia , Fibrose Retroperitoneal/diagnóstico por imagem , Fibrose Retroperitoneal/patologia , Espaço RetroperitonealRESUMO
Mono(ADP-ribosyl)ation and poly(ADP-ribosyl)ation are posttranslational modifications evolutionarily conserved in prokaryotes and eukaryotes. They entail transfer of one or more ADP-ribose moieties from NAD+ to acceptor proteins with the simultaneous release of nicotinamide. The resultant ADP-ribosylated acceptor proteins regulate diverse cellular functions. For instance, ADP-ribosyltransferase 1 (ART1) catalyzes mono(ADP-ribosyl)ation of arginine residues in Trim72, a protein specifically expressed in muscle cells and involved in cell membrane repair, which is enhanced upon its ADP-ribosylation. By contrast, the contribution made by ADP-ribosylation to membrane repair in epithelial cells remains unclear. In this study, we investigated the involvement of ADP-ribosylation in cell membrane repair in HEK293T and HeLa cells. We found that upon induction of membrane damage using streptolysin-O, poly(ADP-ribose) polymerase 1 (PARP1) catalyzed poly(ADP-ribosyl)ation. In scratch assays, inhibition of PARP1 activity using the nonspecific PARP inhibitor PJ34 or shRNA targeting PARP1 delayed wound healing, suggesting that PARP1-catalyzed poly(ADP-ribosyl)ation plays a key role in membrane repair in epithelial cells.
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Poli(ADP-Ribose) Polimerase-1 , Poli ADP Ribosilação , Poli Adenosina Difosfato Ribose , Células HEK293 , Células HeLa , Humanos , Poli(ADP-Ribose) Polimerase-1/genética , Poli(ADP-Ribose) Polimerase-1/metabolismo , Poli Adenosina Difosfato Ribose/metabolismo , Poli(ADP-Ribose) Polimerases/química , Poli(ADP-Ribose) Polimerases/genética , Poli(ADP-Ribose) Polimerases/metabolismoRESUMO
Acetylcholine (ACh) is the classical neurotransmitter in the cholinergic nervous system. However, ACh is now known to regulate various immune cell functions. In fact, T cells, B cells, and macrophages all express components of the cholinergic system, including ACh, muscarinic, and nicotinic ACh receptors (mAChRs and nAChRs), choline acetyltransferase, acetylcholinesterase, and choline transporters. In this review, we will discuss the actions of ACh in the immune system. We will first briefly describe the mechanisms by which ACh is stored in and released from immune cells. We will then address Ca2+ signaling pathways activated via mAChRs and nAChRs on T cells and B cells, highlighting the importance of ACh for the function of T cells, B cells, and macrophages, as well as its impact on innate and acquired (cellular and humoral) immunity. Lastly, we will discuss the effects of two peptide ligands, secreted lymphocyte antigen-6/urokinase-type plasminogen activator receptor-related peptide-1 (SLURP-1) and hippocampal cholinergic neurostimulating peptide (HCNP), on cholinergic activity in T cells. Overall, we stress the fact that ACh does not function only as a neurotransmitter; it impacts immunity by exerting diverse effects on immune cells via mAChRs and nAChRs.
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Imunomodulação , Receptores Muscarínicos/metabolismo , Receptores Nicotínicos/metabolismo , Acetilcolina/metabolismo , Animais , Cálcio/metabolismo , Sinalização do Cálcio , Regulação da Expressão Gênica , Humanos , Sistema Imunitário/imunologia , Sistema Imunitário/metabolismo , Imunidade , Linfócitos/imunologia , Linfócitos/metabolismo , Especificidade de Órgãos , Peptídeos/metabolismo , Peptídeos/farmacologia , Receptores Muscarínicos/genética , Receptores Nicotínicos/genética , Transdução de SinaisRESUMO
We encountered 3 cases of acute kidney injury that occurred after treatment with a SGLT2 inhibitor. In case 1, serum creatinine increased from 1.65 to 3.0 mg/dL, in case 2, serum creatinine increased from 1.03 to 1.21 mg/dL, and in case 3, serum creatinine increased from 0.8 to 1.1 mg/dL. Renal biopsy showed isometric vacuolization on tubules, that was completely negative for Periodic acid-Schiff (PAS) stain in case 1, and was partially negative for PAS stain in case 2 and 3, consistent with osmotic vacuolization. Immunohistochemical analysis showed positive staining for CD138 and CD10 indicating the proximal tubules in the vacuolar lesions. 3 patients were obese with body mass index of more than 30, and showed an increase in serum renin. In conclusion, in type II diabetes mellitus (T2DM), individuals that remain within their standard weight range, SGLT2 inhibitor treatment does not result in osmotic vacuolization of proximal tubular epithelial cells and AKI. However, treatment with a SGLT2 inhibitor may cause damage of the proximal tubules resulting in AKI in T2DM individuals who do not remain within their standard weight range, due to an overdose lavage of sugar in the urine and dehydration.