Hasil untuk "Pathology"

E. Brunt

H. Shimada, I. Ambros, L. Dehner et al.

M. Bradl, H. Lassmann

Oligodendrocytes are the myelinating cells of the central nervous system (CNS). They are the end product of a cell lineage which has to undergo a complex and precisely timed program of proliferation, migration, differentiation, and myelination to finally produce the insulating sheath of axons. Due to this complex differentiation program, and due to their unique metabolism/physiology, oligodendrocytes count among the most vulnerable cells of the CNS. In this review, we first describe the different steps eventually culminating in the formation of mature oligodendrocytes and myelin sheaths, as they were revealed by studies in rodents. We will then show differences and similarities of human oligodendrocyte development. Finally, we will lay out the different pathways leading to oligodendrocyte and myelin loss in human CNS diseases, and we will reveal the different principles leading to the restoration of myelin sheaths or to a failure to do so.

K.R.Aneja

G. Lavigne, S. Khoury, S. Abe et al.

W. Brown, C. Thore

V. Johnson, W. Stewart, Douglas H. Smith

E. Stacher, B. Graham, J. M. Hunt et al.

D. E. Mills

J. Glausier, D. Lewis

Fernando N. Martín Cocilova, Elisabetta Neri, Filippo Nozzoli et al.

Pseudomyogenic hemangioendothelioma (PHME) is a very rare vascular tumor that usually arises in the extremities, mainly cutaneous or subcutaneous, but also occurs in deeper locations, such as muscles and bone. Less than 200 cases have been reported so far, and primary intraosseous PHMEs are further infrequent. We present a clinical case of PMHE of the femur in a young male adult successfully treated by intercalary resection and massive allograft reconstruction with plates fixation. After more than 2 years of follow-up, the patient is disease-free and asymptomatic, walking with full weight-bearing with radiographic evidence of allograft union.

Kiziltepe Şemistan, Karakurt Emin, Eser Gizem et al.

Ovine pulmonary adenocarcinoma (OPA) is an infectious and neoplastic disease etiologically linked to the Jaagsiekte sheep retrovirus (JSRV), characterised by tumour lesions of the lung. Because of the economic losses it induces, OPA is of great importance for flock health. In this study, oxidative stress markers and adenosine deaminase (ADA) activity were quantified in lung tissue from sheep, both healthy and those naturally afflicted with OPA. Compared to healthy sheep, malondialdehyde (MDA), nitric oxide (NO ), ceruloplasmin (CP) and ADA concentrations/activities were significantly increased (P<0.05 and P<0.001) in fresh lung tissues from JSRV–infected sheep, while reduced glutathione (GSH) levels were significantly decreased (P<0.05). In conclusion, pronounced oxidative stress and increased ADA enzyme activity were detected in the JSRV–infected sheep. These findings suggest that ADA activity could serve as a biomarker for disease diagnosis.

J. Jennette, J. Olson, M. Schwartz et al.

K. Forbush, J. Wildes, L. Pollack et al.

C. Lucchinetti, Yong Guo, Bogdan F Popescu et al.

Prashasti Agrawal, MD, Michael Offin, MD, Victoria Lai, MD et al.

Introduction: WT1 often presents on the surface of diffuse pleural mesotheliomas (DPMs) and is an ideal therapeutic target. Galinpepimut-S (GPS), a tetravalent, non–human leukocyte antigen–restricted, heteroclitic WT1–specific peptide vaccine was safe and effective in early phase clinical trials and upregulates T-cell suppressive programmed death-ligand 1 in the tumor microenvironment of other malignancies. A randomized phase 2 study of adjuvant GPS in patients with DPM trended toward improved median overall survival. Methods: To further enhance immunogenicity, we combined GPS with nivolumab, an anti-PD1 monoclonal antibody, in an open-label, single-center phase 1 study, examining tolerability and immunogenicity in patients with previously treated DPM. We enrolled patients with progressive or recurrent DPM treated with at least one course of pemetrexed-based chemotherapy. Patients received two doses of GPS followed by six doses of GPS with intravenous nivolumab every 2 weeks, and up to six additional cycles until disease progression or unacceptable toxicity. Results: Ten patients were treated; 70% experienced mostly mild treatment-related adverse events; two experienced a grade 3 or higher adverse event. Three of the 10 patients (30%) reported vaccine-specific T-cell responses. There were no partial responses; three patients had prolonged stable disease with up to 17% decrease in tumor volume. Median progression-free survival was 3.9 months and the median overall survival was 7.4 months. Conclusions: Coadministration of GPS and nivolumab reported a tolerable toxicity profile and induced immune responses in a subset of patients, but initial response and survival benefit were limited possibly owing to the small sample size.

Igbayilola Yusuff Dimeji, Adekola Saheed Ayodeji

Central obesity, atherogenic dyslipidemia, insulin resistance, and hypertension are among the metabolic dysregulations associated with metabolic syndrome (MetS). Insulin resistance and chronic low-grade inflammation are 2 of the many acquired and genetic components that make up the pathophysiology of MetS. MetS is strongly linked to a greater risk of diabetes and cardiovascular disease in the absence of effective treatment. To create effective intervention strategies and preventative techniques, the MetS process needs to be thoroughly examined. Recent research has emphasized the critical roles that metabolic endotoxemia and the gut microbiota play in the pathophysiology of MetS. The manipulation of gut microbiota‒host metabolism interactions has been linked to several factors, including bile acid metabolism, short-chain fatty acid metabolism, and inflammation caused by malfunction of the gut barrier. Pharmacological treatments for the gut microbiota are becoming increasingly popular as treatment alternatives. This brief message highlights some of the most recent developments in pharmaceutical strategies for preventing both gut dysbiosis and systemic low-grade inflammation caused by endotoxemia. Antibiotics, prebiotics, probiotics, synbiotics, postbiotics, and metabolite modulators produced from the microbiota are all used in these tactics. Particular focus is placed on next-generation treatments such as small chemical inhibitors of microbial‒host interactions, bacteriophage therapy, and tailored probiotics. Significance Statement: Pharmacologic alteration of the gut microbiota to target endotoxemia, a major cause of systemic inflammation, is a viable next-generation treatment for metabolic syndrome. These treatments help stop lipopolysaccharide translocation, restore metabolic balance, and improve insulin sensitivity by strengthening the gut barrier and changing the makeup of microbes. This method improves lipid metabolism, decreases chronic inflammation, and targets the underlying causes of disease. As a result, to improve results, treatment is moving from just managing symptoms to changing the disease itself.

María Cristina Franco-Arellanes, Perla Xóchitl Toledo-Valdes, Cynthia Díaz-Hernández et al.

INTRODUCTION: O-GlcNAcylation is a post-translational modification in which a single N-Acetyl-D-Glucosamine (GlcNAc) molecule is added to Ser or Thr residues of proteins. The O-N-acetylglucosaminyl transferase (OGT) enzyme is responsible for adding GlcNAc to the target proteins and N-acetyl-β-D-glucosaminidase (OGA) that removes the GlcNAc residue. O-GlcNAcylation has been described in the pathophysiology of several diseases; however, little has been studied in dental tissue. The aim of the present work is to characterise the product of O-GlcNAcylation and its enzymes at the tissue level in the dental pulp, as well as its expression in dental pulp stem cells (DPSCs) both in situ and in vitro. This enables the recognition of the behaviour of O-GlcNAcylation in pulp tissue without pathology. MATERIAL AND METHODS: Pulp tissue was obtained from 10 healthy donors, and the expression of O-GlcNAc, OGT, and OGA was analysed using immunofluorescence with specific antibodies in different regions of the dental pulp. DPSCs were isolated, cultured, and identified with anti-STRO1 (antibody specific for human CD34+ cells, useful for DPSC identification). The expression of O-GlcNAc in DPSCs was confirmed in vitro through Western blot. Results. Different regions of the dental pulp and DPSCs express O-GlcNAc and the enzymes OGT and OGA. O-GlcNAc and OGT expression was more prominent in the odontoblastic layer, cell-rich zone, and in the central core. OGA was distributed throughout the pulp tissue with lower immunoreactivity compared to OGT. CONCLUSIONS: Our results suggest that O-GlcNAcylation may play a relevant role in human dental pulp homeostasis and in physiology of DPSCs.

Chiara Maria Lavinia Loeffler, Omar S. M. El Nahhas, Hannah Sophie Muti et al.

Abstract Background Homologous recombination deficiency (HRD) is recognized as a pan-cancer predictive biomarker that potentially indicates who could benefit from treatment with PARP inhibitors (PARPi). Despite its clinical significance, HRD testing is highly complex. Here, we investigated in a proof-of-concept study whether Deep Learning (DL) can predict HRD status solely based on routine hematoxylin & eosin (H&E) histology images across nine different cancer types. Methods We developed a deep learning pipeline with attention-weighted multiple instance learning (attMIL) to predict HRD status from histology images. As part of our approach, we calculated a genomic scar HRD score by combining loss of heterozygosity (LOH), telomeric allelic imbalance (TAI), and large-scale state transitions (LST) from whole genome sequencing (WGS) data of n = 5209 patients across two independent cohorts. The model’s effectiveness was evaluated using the area under the receiver operating characteristic curve (AUROC), focusing on its accuracy in predicting genomic HRD against a clinically recognized cutoff value. Results Our study demonstrated the predictability of genomic HRD status in endometrial, pancreatic, and lung cancers reaching cross-validated AUROCs of 0.79, 0.58, and 0.66, respectively. These predictions generalized well to an external cohort, with AUROCs of 0.93, 0.81, and 0.73. Moreover, a breast cancer-trained image-based HRD classifier yielded an AUROC of 0.78 in the internal validation cohort and was able to predict HRD in endometrial, prostate, and pancreatic cancer with AUROCs of 0.87, 0.84, and 0.67, indicating that a shared HRD-like phenotype occurs across these tumor entities. Conclusions This study establishes that HRD can be directly predicted from H&E slides using attMIL, demonstrating its applicability across nine different tumor types.

Lisa E. Gralinski, R. Baric

Respiratory viruses can cause a wide spectrum of pulmonary diseases, ranging from mild, upper respiratory tract infections to severe and life‐threatening lower respiratory tract infections, including the development of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Viral clearance and subsequent recovery from infection require activation of an effective host immune response; however, many immune effector cells may also cause injury to host tissues. Severe acute respiratory syndrome (SARS) coronavirus and Middle East respiratory syndrome (MERS) coronavirus cause severe infection of the lower respiratory tract, with 10% and 35% overall mortality rates, respectively; however, >50% mortality rates are seen in the aged and immunosuppressed populations. While these viruses are susceptible to interferon treatment in vitro, they both encode numerous genes that allow for successful evasion of the host immune system until after high virus titres have been achieved. In this review, we discuss the importance of the innate immune response and the development of lung pathology following human coronavirus infection. © 2014 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.