Hasil untuk "Pathology"

L. Ackerman, J. Rosai

S. Love, H. Coakham

K. Del Tredici, U. Rüb, R. D. de Vos et al.

H. Tapiero, D. Townsend, K. Tew

Yanqing Ding, Hui-jun Wang, Hong Shen et al.

In order to investigate the clinical pathology of severe acute respiratory syndrome (SARS), the autopsies of three patients who died from SARS in Nan Fang Hospital Guangdong, China were studied retrospectively. Routine haematoxylin and eosin (H&E) staining was used to study all of the tissues from the three cases. The lung tissue specimens were studied further with Macchiavello staining, viral inclusion body staining, reticulin staining, PAS staining, immunohistochemistry, ultrathin sectioning and staining, light microscopy, and transmission electron microscopy. The first symptom was hyperpyrexia in all three cases, followed by progressive dyspnoea and lung field shadowing. The pulmonary lesions included bilateral extensive consolidation, localized haemorrhage and necrosis, desquamative pulmonary alveolitis and bronchitis, proliferation and desquamation of alveolar epithelial cells, exudation of protein and monocytes, lymphocytes and plasma cells in alveoli, hyaline membrane formation, and viral inclusion bodies in alveolar epithelial cells. There was also massive necrosis of splenic lymphoid tissue and localized necrosis in lymph nodes. Systemic vasculitis included oedema, localized fibrinoid necrosis, and infiltration of monocytes, lymphocytes, and plasma cells into vessel walls in the heart, lung, liver, kidney, adrenal gland, and the stroma of striated muscles. Thrombosis was present in small veins. Systemic toxic changes included degeneration and necrosis of the parenchyma cells in the lung, liver, kidney, heart, and adrenal gland. Electron microscopy demonstrated clusters of viral particles, consistent with coronavirus, in lung tissue. SARS is a systemic disease that injures many organs. The lungs, immune organs, and systemic small vessels are the main targets of virus attack, so that extensive consolidation of the lung, diffuse alveolar damage with hyaline membrane formation, respiratory distress, and decreased immune function are the main causes of death. Copyright © 2003 John Wiley & Sons, Ltd.

Matthew M. Yeh, E. Brunt

D. Louis

D. Bennett, J. Schneider, Yuxiao Tang et al.

Ruohan Yu, Lina Zhang, Sheng-Guang Li et al.

BackgroundLocalized Scleroderma (LoS), particularly aggressive subtypes such as Deep Morphea (morphea profunda), is a rare chronic autoimmune fibrosing disorder that can extend into the subcutaneous tissue, fascia, and muscle. These deep forms carry a high risk of functional impairment. Tocilizumab (TCZ), an anti-interleukin-6 (IL-6) receptor antibody, has emerged as a promising therapy for severe, refractory cases. However, its reported use typically follows the failure of standard immunosuppressive agents like methotrexate (MTX).Case presentationWe report the case of a 19-year-old male with a rapidly progressive deep morphea of the left lower extremity, with only a two-month history from onset. Initial symptoms included skin hardening, hyperpigmentation, and mild restriction of foot motion. Skin biopsy confirmed deep morphea, showing lymphoplasmacytic inflammation and eosinophilic fibrosis extending into the subcutaneous septa and muscle interstitium. Pre-treatment magnetic resonance imaging (MRI) revealed prominent edema (high T2 signal) in the subcutaneous fat and blurred muscle fascial planes, consistent with active deep inflammation. Uniquely, the patient was seropositive for multiple antiphospholipid antibodies (aPLs), including Lupus Anticoagulant (dRVVT ratio 1.34), anti-phosphatidylserine/prothrombin IgM (143.72 U), β2-glycoprotein I IgM (30.9 CU), and anticardiolipin IgM (28.2 CU). Given the rapid progression and deep tissue involvement, an early intensified combination regimen of TCZ (640 mg IV every 4 weeks), MTX (12.5 mg weekly), high-dose corticosteroids (IV pulses followed by 30 mg/day oral prednisone taper), and prophylactic aspirin (100 mg daily) was initiated. Follow-up MRI at six months showed a marked reduction in the deep tissue edema, correlating with significant clinical improvement in skin induration and tightening by nine months post-treatment. No serious adverse events were observed during follow-up.ConclusionThis case demonstrates the successful outcome of early TCZ-based combination therapy in rapidly controlling the aggressive inflammatory process of an adult deep morphea. The objective radiological response validates this early intervention strategy, which deviates from the typical second-line use of TCZ. Furthermore, the case highlights a rare but clinically important overlap between severe localized scleroderma and multiple aPL seropositivity.

Tian F, Xie N, Sun W et al.

Fangbing Tian,1 Nana Xie,1 Wenjin Sun,2 Wencong Zhang,1 Wenyuan Zhang,1 Jia Chen,1 Qiurong Ruan,3,* Jianxin Song1,* 1Department of Infectious Diseases, Tongji Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 2Department of Infectious Diseases, Ezhou Central Hospital, Ezhou, People’s Republic of China; 3Institute of Pathology, Tongji Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jianxin Song, Department of Infectious Diseases, Tongji Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China, Email songsingsjx@sina.com Qiurong Ruan, Institute of Pathology, Tongji Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China, Email ruanqiurong@sina.comPurpose: Hemophagocytic lymphohistiocytosis (HLH) is a critical syndrome with a high mortality rate. In clinical practice, some patients with fever of unknown origin (FUO) can develop HLH, further complicating the diagnosis and treatment. However, studies on HLH in adults with FUO are limited. This study aimed to investigate the clinical characteristics of adult patients with FUO to facilitate the early identification of those at high risk of developing HLH.Patients and Methods: We collected data from hospitalized patients with FUO between January 2014 and December 2020. Risk factors for HLH in adults with FUO were analyzed using univariate and multivariate analysis.Results: A total of 988 patients with FUO were included in the study. The incidence of HLH in adults with FUO was 6.4%, with hematological tumors being the primary cause. Multivariate analysis indicated that skin rash and elevated alanine aminotransferase, total bilirubin, triglycerides, lactate dehydrogenase, and ferritin levels were independent risk factors for HLH in adults with FUO.Conclusion: This study revealed the incidence rate, etiology distribution, and risk factors for HLH in adults with FUO. Comprehensive assessment of clinical and laboratory data at admission can assist in the early identification of FUO patients at risk for HLH.Keywords: Hemophagocytic lymphohistiocytosis, fever of unknown origin, etiology distribution, risk factors

V. Deshpande, Yoh Zen, John K. C. Chan et al.

Muhammad Ali Bangash, Julie Qiaojin Lin

Aims Local protein synthesis at the synapse is a key determinant of learning and memory and is predicted to be severely disrupted in Alzheimer's disease (AD). Omics approaches have played a key role in deciphering molecular mechanisms underlying AD pathology. However, isolating the transcriptome may be biased due to inherent variations in transcript levels, or by transcription-on-demand models employed by several genes, whereas mass-spec based proteomics approaches fail to capture low abundance peptides. The translatome bypasses these inherent limitations of other omics methods by capturing actively translating mRNA species trapped inside ribosomes and subjecting them to unbiased RNA-seq analysis capturing even very low abundance transcripts. Methods Isolating the neuronal ribosomes from human post-mortem brains without interference from non-neuronal cells remains a challenge. We used frozen brain tissue from Alzheimer's patients and healthy controls obtained from the Cambridge Brain Biobank. Synaptoneurosomal fractions were prepared using sucrose gradients in non-denaturing buffers with RNAse inhibitors to preserve ribosomal composition and trapped mRNA. We isolated functional ribosomes on affinity columns following recombinant RNAse digestion. Finally, actively translating ribosome-trapped mRNAs were sequenced using RNA-seq, aligned to human genome using STAR alignment and analysed for differential expression using DeSeq2 followed by pathway analysis. Results We have successfully isolated ribosome-associated RNA transcripts in the dendritic spines from cortical neurons of postmortem Alzheimer's brains with little interference from glial and non-neuronal material. The novel AD translatome disruptions identified by isolating endogenous ribosome bound mRNA will help detect downstream molecular targets. We will also integrate targeted translatome data with published transcriptome and GWAS DNA variant data to identify novel biomarkers. Conclusion This is the first successful isolation of the dendritic translatome from human postmortem AD brains. Future studies will verify functional significance of key targets using gain- and loss-of-function studies in animal models of AD and human iPSCs.

José Alberto Choreño-Parra, José Alberto Choreño-Parra, Lucero A. Ramon-Luing et al.

IntroductionThe proteolytic activity of A Disintegrin and Metalloproteinase 17 (ADAM17) regulates the release of tumor necrosis factor (TNF) and TNF receptors (TNFRs) from cell surfaces. These molecules play important roles in tuberculosis (TB) shaping innate immune reactions and granuloma formation.MethodsHere, we investigated whether single nucleotide polymorphisms (SNPs) of ADAM17 influence TNF and TNFRs levels in 224 patients with active TB (ATB) and 118 healthy close contacts. Also, we looked for significant associations between SNPs of ADAM17 and ATB status. TNF, TNFR1, and TNFR2 levels were measured in plasma samples by ELISA. Four SNPs of ADAM17 (rs12692386, rs1524668, rs11684747, and rs55790676) were analyzed in DNA isolated from peripheral blood leucocytes. The association between ATB status, genotype, and cytokines was analyzed by multiple regression models.ResultsOur results showed a higher frequency of rs11684747 and rs55790676 in close contacts than ATB patients. Coincidentally, heterozygous to these SNPs of ADAM17 showed higher plasma levels of TNF compared to homozygous to their respective ancestral alleles. Strikingly, the levels of TNF and TNFRs distinguished participant groups, with ATB patients displaying lower TNF and higher TNFR1/TNFR2 levels compared to their close contacts.ConclusionThese findings suggest a role for SNPs of ADAM17 in genetic susceptibility to ATB.

K. Seidel, Sonny Siswanto, E. Brunt et al.

O. Leone, J. Veinot, A. Angelini et al.

Adelaida Lozano Polo, Pedro Simón Cayuela Fuentes, Josep Sánchez Monfort et al.

Introduction Nurses have an essential role in smoking cessation. The Murcia Society of Family and Community Nursing (SEAPREMUR) launched a research project (GRUPALTAB-SEAPREMUR) to analyze the effectiveness of various group interventions to quit smoking, based on health education techniques and whith the App S’Acabó designed by the Spanish Society of Tobacco Specialists (SEDET). Nurses were trained in the protocol used in the interventions. Objective To compare the effectiveness of group interventions to quit smoking in the short and long term. Analyze the utility of the App to encourage smoking cessation. Material and Methods Multicenter randomized clinical trial conducted in Primary Care Center (PCC) in the Region of Murcia from 2018 to 2020 in two phases (P). Inclusion criteria: Being over 18 years old, wanting to quit smoking, speaking Spanish, having Internet access. Exclusion: Polydrug use, pregnant women or psychiatric pathology. The sample size was calculated and randomly assigned to the type of intervention. Interventions: Workshop of 2 to 4 hours inly session vs Course of 4 sessions of 2 hours duration for 1 month. The smoking abstinence at three months and one year (prevalence and OR; 95%CI) is calculated with SPSSV21, comparing the population that uses or not the App. Results In 2018, the study (P1) started in 8 PPC 228 participants: 54.2% women. They were followed-up for one year: 83 (46.1%). In 2019, the second phase (P2) was carried out in 16 PCC, with a shorter workshop (2:30h) and the same course (296 participants; 59.2% women) Global abstinence at 3 months (P1: 23.8%; P2: 20.9%) and at 12 months (P1: 31.7%). No significant statistical differences were observed in smoking cessation by sex, social class, or type of intervention, although abstinence was lower in the workshop: - P1 Workshop vs Course. OR at 3 months: 0.89 (95%CI: 0.38-2.08) OR at 12 months: 0.83 (95%CI: 0.32-2.57). - P2 Workshop vs Course. OR at 3 months: 0.61 (95%CI: 0.29-1.29). Use of App (P1: 42.1%; P2: 42.6%). An increase in quit attempts was observed in those who used the App compared to those who did not (P1 at 12 months: (37.7% vs 14.3%; p=0.047); P2 at 3 months: (54.5% vs 45.5%, p=0.01). Conclusions 1. Group smoking cessation interventions conducted by nurses are effective. 2. No significant differences were observed by type of group intervention. 3. The use of the App promotes quit attempts.

Pauline van Schouwenburg, Pauline van Schouwenburg, Susanne Unger et al.

Common variable immunodeficiency (CVID), characterized by recurrent infections, low serum class-switched immunoglobulin isotypes, and poor antigen-specific antibody responses, comprises a heterogeneous patient population in terms of clinical presentation and underlying etiology. The diagnosis is regularly associated with a severe decrease of germinal center (GC)-derived B-cell populations in peripheral blood. However, data from B-cell differentiation within GC is limited. We present a multiplex approach combining histology, flow cytometry, and B-cell receptor repertoire analysis of sorted GC B-cell populations allowing the modeling of distinct disturbances in GCs of three CVID patients. Our results reflect pathophysiological heterogeneity underlying the reduced circulating pool of post-GC memory B cells and plasmablasts in the three patients. In patient 1, quantitative and qualitative B-cell development in GCs is relatively normal. In patient 2, irregularly shaped GCs are associated with reduced somatic hypermutation (SHM), antigen selection, and class-switching, while in patient 3, high SHM, impaired antigen selection, and class-switching with large single clones imply increased re-cycling of cells within the irregularly shaped GCs. In the lymph nodes of patients 2 and 3, only limited numbers of memory B cells and plasma cells are formed. While reduced numbers of circulating post GC B cells are a general phenomenon in CVID, the integrated approach exemplified distinct defects during GC maturation ranging from near normal morphology and function to severe disturbances with different facets of impaired maturation of memory B cells and/or plasma cells. Integrated dissection of disturbed GC B-cell maturation by histology, flow cytometry, and BCR repertoire analysis contributes to unraveling defects in the essential steps during memory formation.

Martin Dreyling, Marc André, Nicola Gökbuget et al.

Sarah M. Alghamdi, Paul N. Schofield, Robert Hoehndorf

Computing phenotypic similarity helps identify new disease genes and diagnose rare diseases. Genotype–phenotype data from orthologous genes in model organisms can compensate for lack of human data and increase genome coverage. In the past decade, cross-species phenotype comparisons have proven valuble, and several ontologies have been developed for this purpose. The relative contribution of different model organisms to computational identification of disease-associated genes is not fully explored. We used phenotype ontologies to semantically relate phenotypes resulting from loss-of-function mutations in model organisms to disease-associated phenotypes in humans. Semantic machine learning methods were used to measure the contribution of different model organisms to the identification of known human gene–disease associations. We found that mouse genotype–phenotype data provided the most important dataset in the identification of human disease genes by semantic similarity and machine learning over phenotype ontologies. Other model organisms' data did not improve identification over that obtained using the mouse alone, and therefore did not contribute significantly to this task. Our work impacts on the development of integrated phenotype ontologies, as well as for the use of model organism phenotypes in human genetic variant interpretation. This article has an associated First Person interview with the first author of the paper.

Takayasu Ito, Yasushi Makino, Shuko Mashimo et al.

Abstract A 59‐year‐old woman complained of continuous dyspnea. Computed tomography revealed multiple pulmonary nodules, mildly small enlarged mediastinal lymph nodes and a nodule in the liver segment 8. Her dyspnea worsened with respiratory failure 4 days after presentation. Liver biopsy was not possible as she could not hold her breath; thus, we performed bronchoscopy. For biopsy, the pulmonary nodules with a positive bronchus sign were preferred over the mildly small enlarged mediastinal lymph nodes. Bronchoscopy under non‐invasive positive pressure ventilation (NPPV) or high‐flow nasal cannula (HFNC) was impossible because of the lack of equipment. Therefore, we biopsied via thin bronchoscope through nasal cavity under a high‐concentration oxygen mask. Pathological findings revealed epidermal growth factor receptor mutation‐positive lung adenocarcinoma. For patients with respiratory failure who cannot undergo bronchoscopy under NPPV or HFNC, thin bronchoscopy through the nasal cavity under a high‐concentration oxygen mask may be clinically useful to prevent hypoxaemia during the procedure