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Journal of Clinical and Experimental... 2024In the new WHO classifications of haematolymphoid tumours (WHO-HAEM5), classic Hodgkin lymphoma (cHL) is categorized into B-cell lymphoid proliferations and lymphomas....
In the new WHO classifications of haematolymphoid tumours (WHO-HAEM5), classic Hodgkin lymphoma (cHL) is categorized into B-cell lymphoid proliferations and lymphomas. Although the majority of Hodgkin Reed-Sternberg (HRS) cells are of germinal center B-cell origin with some defects of B-cell transcription factors, they rarely express T-cell antigens or cytotoxic molecules. Clonality analyses on cHL samples using BIOMED-2 have been reported by several groups; however, those studies were only focused on Ig regions, including IgH, Ig-kappa, and Ig-lambda, and TCR-γ clonality analysis of cHL has not yet been explored. Here, we investigated TCR-γ gene rearrangement for one hundred cases using a PCR-based method. Four of one hundred (4%) cases showed TCR-γ clonal peaks. Of these, three were at an advanced stage and one patient died of the disease. To clarify whether HRS cells showed T-cell clonality or not, we performed PCR analysis using DNAs of microdissected HRS cells. Three samples showed identical clonal peaks with bulk specimens. Our results indicate that cHL is a heterogeneous disease of mainly B-cell and rarely T-cell origin with a special phenotype. Further molecular studies are warranted.
Topics: Humans; Hodgkin Disease; Male; Adult; Female; Middle Aged; Aged; Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor; Paraffin Embedding; Aged, 80 and over; Adolescent; Receptors, Antigen, T-Cell, gamma-delta; Reed-Sternberg Cells; Young Adult; Polymerase Chain Reaction
PubMed: 38925974
DOI: 10.3960/jslrt.24027 -
The Journal of Veterinary Medical... Jun 2024Sarcocystis spp. cause pigeon protozoan encephalitis, a neuronal disease. A female pigeon exhibiting torticollis had a necrotic area in the cerebral hemisphere...
Sarcocystis spp. cause pigeon protozoan encephalitis, a neuronal disease. A female pigeon exhibiting torticollis had a necrotic area in the cerebral hemisphere surrounded by lesions with perivascular cuffing, gliosis, granulomatous foci, and meningitis. Non-necrotic lesions were also observed in the brainstem. Intact and degenerative schizonts were observed within the neuropils and neurons in the lesions. Deoxyribonucleic acid (DNA) was extracted from paraffin-embedded brain tissues and genetically analyzed after gel electrophoresis to determine Sarcocystis spp. using specific primer sets for 28S ribosomal ribonucleic acid and internal transcribed spacer region-1. DNA sequencing confirmed a significant homology with S. calchasi. This is the first report of meningoencephalitis with malacia caused by S. calchasi in a rock pigeon in Japan.
PubMed: 38925932
DOI: 10.1292/jvms.24-0069 -
Journal of Invertebrate Pathology Jun 2024The oomycete Aphanomyces astaci is the causative agent of crayfish plague, a disease threatening susceptible freshwater crayfish species in Europe. To detect its...
The oomycete Aphanomyces astaci is the causative agent of crayfish plague, a disease threatening susceptible freshwater crayfish species in Europe. To detect its spatiotemporal occurrence in Switzerland, we reviewed (1) the literature regarding occurrence of crayfish plague and North American crayfish carrier species and (2) the necropsy report archive of the Institute for Fish and Wildlife Health (FIWI) from 1968 to 2020. In the past, crayfish plague was diagnosed through several methods: conventional PCR, culture, and histology. When available, we re-evaluated archived Bouin's or formalin-fixed, paraffin-embedded samples collected during necropsies (1991-2020) with a recently published quantitative PCR. Literature research revealed putative reports of crayfish plague in Switzerland between the 1870s and 1910s and the first occurrence of three North American crayfish species between the late 1970s and 1990s. Finally, 54 (28.1%) cases were classified as positive and 9 (4.7%) cases as suspicious. The total number of positive cases increased by 14 (14.7%) after re-evaluation of samples. The earliest diagnosis of crayfish plague was performed in 1980 and the earliest biomolecular confirmation of A. astaci DNA dated 1991. Between 1980-1990, 1991-2000 and 2001-2010 crayfish plague spread from one to two and finally three catchment basins, respectively. Similar to other European countries, crayfish plague has occurred in Switzerland in two waves: the first at the end of the 19th and the second at the end of the 20th century in association with the first occurrence of North American crayfish species. The spread from one catchment basin to another suggests a human-mediated pathogen dispersal.
PubMed: 38925366
DOI: 10.1016/j.jip.2024.108159 -
Waste Management (New York, N.Y.) Jun 2024Multilayer film packaging (MLP) waste was decomposed completely at 500 °C. Catalysts were employed to convert residue polymer to waxes via pyrolysis at 500 °C. The...
Multilayer film packaging (MLP) waste was decomposed completely at 500 °C. Catalysts were employed to convert residue polymer to waxes via pyrolysis at 500 °C. The activities achieved from using mordenite (Si/Al = 10), H-ZSM-5 (Si/Al = 25), MCM-41, and Al-MCM-41 (Si/Al ratio of 25, 50, and 75) catalysts were studied. The yield and property of the wax were improved with the use of the catalysis with various acidity and porous structure. The low yield of the waxes, when using mordenite and H-ZSM-5 catalysts, was caused by the microporous structure and strong acidic properties of the catalysts resulting in larger amount of gas production. The MCM-41 catalyst modified with various aluminum content raised the wax yield to 60 %. Al-MCM-41(50) produced the largest amount of wax when compared to Al-MCM-41(25), Al-MCM-41(75), and MCM-41. The mild acidity and mesoporous structure of Al-MCM-41(50) significantly enhanced the paraffins structure of the obtained waxes over other structures, while lower Si/Al ratios favored the conversion of paraffins toward olefin structure. The pyrolysis of MLP with Al-MCM-41(50) produced paraffins and olefins with the middle carbon ranging (C11-20) which were similar quality to pharmaceutical grade of petroleum wax. The spent catalysts of Al-MCM-41 series gradually decreased in wax yield and paraffins composition during the sequential MLP pyrolysis; however, the activity of catalysts was recovered after calcination of the spent catalysts. Furthermore, the viscosity of waxes obtained from Al-MCM-41(50) was 2384 Pa.s at 25 °C similar to the viscosity from commercial petroleum jelly base of 2333 Pa.s.
PubMed: 38924981
DOI: 10.1016/j.wasman.2024.06.012 -
Pathology, Research and Practice Jun 2024The purpose was to detected features of the expression levels of NKG2A and its ligand HLA-E, a new member of the immune checkpoints, in advanced laryngeal carcinoma and...
OBJECTIVES
The purpose was to detected features of the expression levels of NKG2A and its ligand HLA-E, a new member of the immune checkpoints, in advanced laryngeal carcinoma and their clinicopathologic significance.
MATERIAL AND METHODS
We analyzed the expression levels of HLA-E and NKG2A in multiple types of tumors utilizing the Tumor Immune Estimation Resource (TIMER) database and immunohistochemistry and qRT-PCR analysis of paraffin embedded tissue samples to reveal the correlations of the clinicopathological factors with the expression of these two proteins in advanced laryngeal carcinoma as well as their prognostic significance.
RESULTS
KLRC1 (the coding gene of NKG2A) and HLA-E are substantially overexpressed in various human cancers than normal tissues. HNSCC is also included. KLRC1 is differentially expressed in different HPV subgroups of patients, with higher expression in the HPV-positive group. Consistent with this, immunohistochemical results also revealed the high expression of these two proteins in tumor tissue. In addition, immunohistochemical staining also displayed a preference for the distribution of NKG2A-positive cells in tumor tissue. Clinicopathological analyses also displayed that the density of NKG2A-positive cells of the HPV-positive group infiltrating laryngeal carcinoma tissue was larger than that in the HPV-negative group. Prognostic analyses indicated that the expression of this immune checkpoint does not affect the overall survival length of patients, but the highly expressed HLA-E is significantly correlated with local recurrence in the patients.
CONCLUSIONS
The findings suggest that the expression levels of HLA-E and NKG2A is upregulated in advanced laryngeal carcinoma. The NKG2A-positive cells infiltrating the tumor are mainly distributed in the cancer nest, while infiltrating cell number may be regulated by HPV. The highly expressed HLA-E may promote local recurrence in patients with advanced laryngeal carcinoma.
PubMed: 38924853
DOI: 10.1016/j.prp.2024.155383 -
Water Research Jun 2024Sewage sludge adsorbs a large amount of harmful organic pollutants, particularly the persistent and hydrophobic polyhalogenated compounds (PHCs). PHCs have been...
Sewage sludge adsorbs a large amount of harmful organic pollutants, particularly the persistent and hydrophobic polyhalogenated compounds (PHCs). PHCs have been subjected to biological and chemical oxidation treatments during wastewater treatment processes; however, the species and concentrations of their transformation products (TPs) in sludge remain unknown, and the transformation pathways are unclear. In this study, 234 TPs of PHCs, including 77 TPs of chlorinated paraffins (CPs-TPs), 102 TPs of organochlorine pesticides (OCPs-TPs), 45 TPs of dechlorane plus (DPs-TPs), and 10 TPs of brominated flame retardants (BFRs-TPs), were identified in sludge through PhPCl-enhanced ionization coupled with ultra-performance liquid chromatography-Orbitrap-mass spectrometry. Based on the chemical structures of the identified TPs, we identified three major transformation pathways: dehalogenation-hydroxylation, carbon chain decomposition, and desulfurization. Approximately 97 TPs were newly discovered through the pathways. Carbon chain decomposition products of OCPs and DPs were detected for the first time at relatively high abundances. More hydroxylation products of DPs and hexabromocyclododecane (HBCD) and multi-dehalogenation products of heptachlor, toxaphene, DPs and HBCDs were detected at relative intensities higher than those of the known TPs. The oxidation treatment of sludge achieved up to 13 %-94 % of PHCs to be removed, with dehalogenation-hydroxylation as the main transformation pathway. Advanced treatment technologies are needed for degradation of both PHCs and their TPs.
PubMed: 38924808
DOI: 10.1016/j.watres.2024.121978 -
The British Journal of Dermatology Jun 2024Primary cutaneous acral CD8+ T-cell lymphoproliferative disorder (TLPD) is a rare and indolent lymphoma entity. Although known for years, the molecular pathogenesis is...
BACKGROUND
Primary cutaneous acral CD8+ T-cell lymphoproliferative disorder (TLPD) is a rare and indolent lymphoma entity. Although known for years, the molecular pathogenesis is still unknown.
OBJECTIVES
In order to better understand the molecular pathogenesis of cutaneous acral CD8+ TLPD and to identify further discriminatory markers to discern this lymphoma subtype from further CD8+ cutaneous lymphomas, we analysed five cases of cutaneous acral CD8+ TLPD for putative molecular alterations.
METHODS
Somatic alterations were assessed by whole exome and targeted sequencing of paraffin-embedded tissue. Results were evaluated by immunohistochemical staining of respective relevant proteins. CD8+ cutaneous T-cell lymphomas (n = 12) served as control for KIR3DL1-staining.
RESULTS
Copy number variations (CNV) analysis revealed a homozygous deletion of the KIR3DL1 gene in two of the analysed cases. This resulted in loss of KIR3DL1 protein expression which was observed in all cases of cutaneous acral CD8+ TLPD. In contrast, KIR3DL1 expression was more variable in other CD8+ cutaneous T-cell lymphomas with 50% of analysed cases (n = 12) being positive. In addition, one further case of acral CD8+ TLPD harboured a loss of function mutation in the PIK3R1 gene presumably activating the PI3K-AKT pathway.
CONCLUSION
Alterations of KIR3DL1 gene may be of pathogenetic relevance for acral CD8+ TLPD. Loss of KIR3DL1 protein expression may support the diagnosis of this indolent lymphoma entity, albeit not being a subtype-specific discriminative feature.
PubMed: 38924750
DOI: 10.1093/bjd/ljae256 -
The Journal of Pathology. Clinical... Jul 2024Tumor structure is heterogeneous and complex, and it is difficult to obtain complete characteristics by two-dimensional analysis. The aim of this study was to visualize...
Tumor structure is heterogeneous and complex, and it is difficult to obtain complete characteristics by two-dimensional analysis. The aim of this study was to visualize and characterize volumetric vascular information of clear cell renal cell carcinoma (ccRCC) tumors using whole tissue phenotyping and three-dimensional light-sheet microscopy. Here, we used the diagnosing immunolabeled paraffin-embedded cleared organs pipeline for tissue clearing, immunolabeling, and three-dimensional imaging. The spatial distributions of CD34, which targets blood vessels, and LYVE-1, which targets lymphatic vessels, were examined by calculating three-dimensional density, vessel length, vessel radius, and density curves, such as skewness, kurtosis, and variance of the expression. We then examined those associations with ccRCC outcomes and genetic alteration state. Formalin-fixed paraffin-embedded tumor samples from 46 ccRCC patients were included in the study. Receiver operating characteristic curve analyses revealed the associations between blood vessel and lymphatic vessel distributions and pathological factors such as a high nuclear grade, large tumor size, and the presence of venous invasion. Furthermore, three-dimensional imaging parameters stratified ccRCC patients regarding survival outcomes. An analysis of genomic alterations based on volumetric vascular information parameters revealed that PI3K-mTOR pathway mutations related to the blood vessel radius were significantly different. Collectively, we have shown that the spatial elucidation of volumetric vasculature information could be prognostic and may serve as a new biomarker for genomic alterations. High-end tissue clearing techniques and volumetric immunohistochemistry enable three-dimensional analysis of tumors, leading to a better understanding of the microvascular structure in the tumor space.
Topics: Humans; Carcinoma, Renal Cell; Kidney Neoplasms; Female; Male; Microvessels; Middle Aged; Aged; Imaging, Three-Dimensional; Biomarkers, Tumor; Neovascularization, Pathologic; Adult; Prognosis
PubMed: 38923836
DOI: 10.1002/2056-4538.12388 -
Proteomics. Clinical Applications Jun 2024Diabetic kidney disease (DKD) is a serious complication of diabetes mellitus and a leading cause of chronic kidney disease and end-stage renal disease. One potential...
PURPOSE
Diabetic kidney disease (DKD) is a serious complication of diabetes mellitus and a leading cause of chronic kidney disease and end-stage renal disease. One potential mechanism underlying cellular dysfunction contributing to kidney disease is aberrant protein post-translational modifications. Lysine acetylation is associated with cellular metabolic flux and is thought to be altered in patients with diabetes and dysfunctional renal metabolism.
EXPERIMENTAL DESIGN
A novel extraction and LC-MS/MS approach was adapted to quantify sites of lysine acetylation from formalin-fixed paraffin-embedded (FFPE) kidney tissue and from patients with DKD and non-diabetic donors (n = 5 and n = 7, respectively).
RESULTS
Analysis of FFPE tissues identified 840 total proteins, with 225 of those significantly changing in patients with DKD. Acetylomic analysis quantified 289 acetylated peptides, with 69 of those significantly changing. Pathways impacted in DKD patients revealed numerous metabolic pathways, specifically mitochondrial function, oxidative phosphorylation, and sirtuin signaling. Differential protein acetylation in DKD patients impacted sirtuin signaling, valine, leucine, and isoleucine degradation, lactate metabolism, oxidative phosphorylation, and ketogenesis.
CONCLUSIONS AND CLINICAL RELEVANCE
A quantitative acetylomics platform was developed for protein biomarker discovery in formalin-fixed and paraffin-embedded biopsies of kidney transplant patients suffering from DKD.
PubMed: 38923810
DOI: 10.1002/prca.202400018 -
Molecular Oncology Jun 2024Endometrioid ovarian cancers (EOvC) are usually managed as serous tumors. In this study, we conducted a comprehensive molecular investigation to uncover the distinct...
Endometrioid ovarian cancers (EOvC) are usually managed as serous tumors. In this study, we conducted a comprehensive molecular investigation to uncover the distinct biological characteristics of EOvC. This retrospective multicenter study involved patients from three European centers. We collected clinical data and formalin-fixed paraffin-embedded (FFPE) samples for analysis at the DNA level using panel-based next-generation sequencing and array-comparative genomic hybridization. Additionally, we examined mRNA expression using NanoString nCounter® and protein expression through tissue microarray. We compared EOvC with other ovarian subtypes and uterine endometrioid tumors. Furthermore, we assessed the impact of molecular alterations on patient outcomes, including progression-free survival (PFS) and overall survival (OS). Preliminary analysis of clinical data from 668 patients, including 86 (12.9%) EOvC, revealed more favorable prognosis for EOvC compared with serous ovarian carcinoma (5-year OS of 60% versus 45%; P = 0.001) driven by diagnosis at an earlier stage. Immunohistochemistry and copy number alteration (CNA) profiles of 43 cases with clinical data and FFPE samples available indicated that EOvC protein expression and CNA profiles were more similar to endometrioid endometrial tumors than to serous ovarian carcinomas. EOvC exhibited specific alterations, such as lower rates of PTEN loss, mutations in DNA repair genes, and P53 abnormalities. Survival analysis showed that patients with tumors harboring loss of PTEN expression had worse outcomes (median PFS 19.6 months vs. not reached; P = 0.034). Gene expression profile analysis confirmed that EOvC differed from serous tumors. However, comparison to other rare subtypes of ovarian cancer suggested that the EOvC transcriptomic profile was close to that of ovarian clear cell carcinoma. Downregulation of genes involved in the PI3K pathway and DNA methylation was observed in EOvC. In conclusion, EOvC represents a distinct biological entity and should be regarded as such in the development of specific clinical approaches.
PubMed: 38923749
DOI: 10.1002/1878-0261.13679