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doi: 10.1111/apm.13408pmid: 38757248
The Melan‐A (melanocyte antigen) protein, also termed ‘melanoma antigen recognized by T cells 1’ (MART‐1) is a protein with unknown function whose expression is specific for the melanocyte lineage. Antibodies against Melan‐A are thus used for identifying melanocytic tumors, but some Melan‐A antibodies show an additional – diagnostically useful – cross‐reactivity against an unspecified protein involved in corticosteroid hormone synthesis. To comprehensively compare the staining patterns of a specific and a cross‐reactive Melan‐A antibody in normal and neoplastic tissues, tissue microarrays containing 15,840 samples from 133 different tumor types and subtypes as well as 608 samples of 76 different normal tissue types were analyzed by immunohistochemistry. For the Melan‐A‐specific antibody ‘Melan‐A specific’ (MSVA‐900M), Melan‐A positivity was seen in 96.0% of 25 benign nevi, 93.0% of 40 primary and 86.7% of 75 metastatic melanomas, 82.4% of 85 renal angiomyolipomas as well as 96.4% of 84 neurofibromas, 2.2% of 46 granular cell tumors, 1.0% of 104 schwannomas, and 1.1% of 87 leiomyosarcomas. The cross‐reactive antibody ‘Melan‐A+' (MSVA‐901M+) stained 98.1% of the tumors stained by ‘Melan‐A specific’. In addition, high positivity rates were seen in sex‐cord‐stroma tumors of the ovary (35.3%–100%) and the testis (86.7%) as well as for adrenocortical neoplasms (76.3%–83.0%). Only nine further tumor groups showed Melan‐A+ staining, including five different categories of urothelial carcinomas. Our data provide a comprehensive overview on the staining patterns of specific and cross‐reactive Melan‐A antibodies. The data demonstrate that both antibodies are highly useful for their specific purpose. It is important for pathologists to distinguish these two Melan‐A antibody subtypes for their daily work.
Maaland, Marit Gaastra; Jakobsen, Lotte; Guardabassi, Luca; Frimodt‐Møller, Niels
doi: 10.1111/apm.13409pmid: 38558445
The antimicrobial agent nitrofurantoin is becoming increasingly important for treatment of urinary tract infections (UTIs) due to widespread occurrence of multidrug‐resistant Escherichia coli. Despite many years of use, little data on nitrofurantoin pharmacokinetics (PK) or ‐dynamics (PD) exist. The objective of this study was to (i) evaluate the pharmacokinetics of nitrofurantoin in a mouse model and (ii) use that data to design an in vivo dose fractionation study in an experimental model of UTI with E. coli for determination of the most predictive PK/PD index. Nitrofurantoin concentrations in urine were approximately 100‐fold larger than concentrations in plasma after oral administration of 5, 10, and 20 mg/kg nitrofurantoin. The area under the curve over the minimum inhibitory concentration (AUC/MIC) was weakly correlated to bacterial reduction in urine (r2 = 0.24), while no such correlation was found for the time that nitrofurantoin stayed above the MIC (T > MIC). Increasing size of single‐dose treatment was significantly correlated to eradication of bacteria in the urine, while this was not apparent when the same doses were divided in 2 or 3 doses 8 or 12 h apart. In conclusion, the results indicate that nitrofurantoin activity against E. coli in urine is driven by AUC/MIC.
Astari, Dian Ekayanti; Massi, Muhammad Nasrum; Masadah, Rina; Hardjo, Marhaen; Natzir, Rosdiana; Erlichster, Michael; Chana, Gursharan; Skafidas, Efstratios; Seraj, Zeba Islam; Elias, Sabrina M.; Soraya, Gita Vita
doi: 10.1111/apm.13415pmid: 38659394
Reverse transcription loop‐mediated isothermal amplification (RT‐LAMP) is a molecular amplification method that can detect SARS‐CoV‐2 in a shorter time than the current gold‐standard molecular diagnostic reverse transcription‐polymerase chain reaction (RT‐PCR). However, previously developed RT‐LAMP assays have mostly relied on highly subjective visual colorimetric interpretation. In this study, an RT‐LAMP assay was developed with quantitative measurement of reaction pH using a novel portable pH biosensor compared to qualitative colorimetric interpretation and gel electrophoresis, with 57 clinical COVID‐19 samples used for validation of the test. The LoD of the assay is 103 copies/μL. The highest sensitivity was found in the qualitative methods (93.75%), while the highest specificity and likelihood ratio was found in the pH sensor (87.5% and 6.72). On the sensor measurement, a significant difference (p < 0.0001) was observed between the average pH of the RT‐PCR (+) COVID‐19 (6.15 ± 0.27), while the average pH of the RT‐PCR (−) samples (6.72 ± 0.22). Correlation analysis revealed a strong correlation (r = 0.78, p < 0.0001) between the Ct values obtained from RT‐PCR with the biosensor pH readout. RT‐LAMP with the quantitative pH sensor readout method has the potential to be further developed as an objective molecular assay for rapid and simple detection of SARS‐CoV‐2.
Jiang, Linsen; Qi, Anning; Yang, Hongyu; Wang, Shuping; Wang, Fei; Bai, Xuemei; Ren, Juan
doi: 10.1111/apm.13410pmid: 38644557
LncRNAs play an important role in autoimmune diseases. The purpose of this study was to explore the role of lncRNA SNHG1 in systemic lupus erythematosus (SLE), and laid a theoretical foundation for the study of SLE. The basic clinical information of all subjects was first collected for statistical analysis, and SNHG1 expression in the serum of all subjects was detected by RT‐qPCR. The value of SNHG1 in the diagnosis of SLE was assessed by ROC. The correlation between SNHG1 and each blood sample index was analyzed by Pearson correlation analysis. The role of SNHG1 in primary peripheral blood mononuclear cells (PBMCs) apoptosis was explored. SNHG1 expression is relatively upregulated in patients with SLE compared to healthy people. SNHG1 expression was positively correlated with SLEDAI score, IgG, CRP, and ESR, and negatively correlated with C3 and C4. ROC indicated that SNHG1 has the potential to assist in the diagnosis of SLE. PBMCs apoptosis in SLE was higher than that in control group, the knockdown and overexpression of SNHG1 could correspondingly inhibit and promote PBMCs apoptosis. SNHG1 has the potential to be a diagnosis marker for SLE and may be involved in regulating PBMCs apoptosis.
Teräsjärvi, Johanna T.; Toivonen, Laura; Mertsola, Jussi; Peltola, Ville; He, Qiushui
doi: 10.1111/apm.13411pmid: 38566447
The ST2/IL‐33 signaling pathway has an important role in the host inflammatory response. Here we aimed to study the association of ST2 and IL‐33 polymorphisms with serum soluble (s) ST2 and IL‐33 concentrations in healthy Finnish children and, in addition, their association with childhood asthma. In total, 146 children were followed from birth to the age 7 years for the development of asthma. Single‐nucleotide polymorphisms (SNPs) in ST2 and IL‐33 were determined, and associations of the SNP variants with serum levels of sST2 and IL‐33 at age of 13 months and with recurrent wheezing and childhood asthma at 7 years of age were analyzed. Children with ST2 rs1041973 AC/AA genotypes had significantly lower level of serum sST2 (2453 pg/mL; IQR 2265) than those with CC genotype (5437 pg/mL; IQR 2575; p = < 0.0001). Similar difference was also observed with ST2 rs13408661. No differences were observed between subjects with studied IL‐33 SNPs. Children who carried genetic variants of ST2 rs1041973 or rs13408661 seemed to have a higher risk of asthma. In contrast, children who carried genetic variants of IL‐33 rs12551268 were less often diagnosed with asthma. Even though these SNPs seemed to associate with asthma, the differences were not statistically significant.
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