Rinsho byori. The Japanese journal of clinical pathology最新文献

Presently we, Keio Endocrine and Metabolite Survey (KEMS) study group conducted a questionnaire sur- vey with respect to panic values in the laboratories belonging to Keio University-associated hospitals. As to the initial setting, most of the laboratories answered to play a leading role in preparing the necessary matters to implementation of panic values and revise them corresponding to physician's request on each occasion. In almost all laboratories, they did not verify whether the notification procedure does work to exert appropriate clinical action. The numbers of critical values answered by the 18 laboratories distributed widely in the test items (8-39) and their critical limits (10-68). As to the critical limits, the lower limits of serum K and blood glucose converged among the laboratories, however, the limits of other test items diverged. The results of the present survey regarding to critical values, although being in small scale, may submit the im- portant issue to be solved in near future. [Short Communication].

It was long considered that.D-amino acids were either unnatural isomers or laboratorial artifacts, and that the important functions of amino acids were exerted only by L-amino acids. However, recent investigations have shown that a variety of D-amino acids are present in various organisms, including mammals, and that they play important roles in physiological functions in the body. Here, we present an overview of recent studies of free D-amino acids, focusing on the expression and localization in tissues and cells, biological and physiological activities, biosynthesis, cellular transport, and degradation. From the point of view of human pathophysiology, the possible relevance of free D-amino acids to disease is also described. [Review].

During the exploration of factors that interfere with the erythropoietin (EPO) -EPO receptor (EPOR) interaction in anemia, a novel inhibitory factor of EPO, anti-EPOR antibody, has been detected in anemic pa- tients with immune-mediated diseases. The study also demonstrated that the antibodies were observed in some patients with chronic kidney disease (CKD). EPOR is known to be expressed not only in bone mar- row erythroblasts, but also in other organs including the kidneys. In addition, previous studies showed that EPO may contribute to protecting the kidneys from injury by binding EPOR on renal resident cells as well as through the correction of anemia. Based on this background, we recently examined the clinical significance of anti-EPOR antibodies in patients with CKD. With regard to patients with lupus nephritis, who showed the highest antibody levels among the patients examined, the antibodies were associated with overall disease activity and cell infiltration in the injured kidney, and they were inversely related to the preserved renal function. Here, we discuss the discovery of anti-EPOR antibodies in patients with anemia and CKD, and the possibil- ity of their use as an additional biomarker for the deterioration of the renal function. [Review].

FMS-like tyrosine kinase 3 (FLT3), a class III tyrosine kinase receptor, plays an important role in the pro- liferation, survival, and differentiation of hematopoietic stem/progenitor cells. Approximately 30% of pa- tients with cytogenetically normal acute myeloid leukemia (CN-AML) harbor FLT3 mutations. The most frequent FLT3 mutations are internal tandem duplications (ITDs) in the juxtamembrane domain. FLT3-ITD mutations cause ligand-independent dimerization of FLT3 and the constitutive activation of its downstream signaling pathways, such as PI3K/AKT, A4APK/ERK, and STAT5, leading to dysregulated cellular prolifera- tion. The relapse risk of CN-AML patients with FLT3-ITD is higher and the overall survival (OS) of such patients is shorter than those of patients with wild-type FLT3. Recently genome-wide studies with next-generation sequencing have suggested that mutational combinations of genes related to signal transduction, transcription, splicing, cancer suppressors, and epigenetics contribute to the pathogenesis of AML. These mutations including FLT3-ITD may be prognostic factors facilitating the risk stratification for CN-AML. The point mutations D835/I836 in the tyrosine kinase domain (TKD) are detected in 5-7% of AML patients. The clinical relevance of these FLT3-TKD mutations remains unclear. FLT3-TKD mutations are detected even in patients treated with FLT3 inhibitors as secondary mutations, suggesting that the mutations are as- sociated with the resistance. Therefore, the detection of these mutations might provide us with the opportunity to consider appropriate treatment for patients. The molecular abnormalities in AML patients give us insights into the pathology of AML and clinically significant information required for the diagnosis, prognosis, and treatment decisions. [Review].

Representative diseases of BCR/ABL-negative myeloproliferative neoplasms (MPN) are polycythemia vera (PV), essential thrombocytosis (ET), and primary myelofibrosis (PMF). It was reported in 2005 that there is a common genetic mutation in Exon 14 of the JAK2 gene in MPN cases. The gene mutation is a point mutation at which the 617th amino acid of the JAK2 protein is substituted from valine to phenylalanine and is referred to as the JAK2 V617F mutation. Subsequently, JAK2 Exon 12 mutation, MPL gene mutation, and CALR gene mutation were detected in 2013, and it was revealed that in almost all cases of BCR/ABL- negative MPN, any gene mutation could be involved as a driver gene mutation. As a result, in the WHO classification 2016, gene mutation analyses of JAK2, MPL, and CALR were incorporated into the diagnostic criteria. Analysis of gene mutation is indispensable for the diagnosis of MPN. Also, its importance as an inspection item is increasing. [Review].

Objective: To develop enzyme-linked immunosorbent assay (ELISA) for measurement of IgM antibody (anti-antibody) against human IgG antibody that is binding to antigen, to distinguish anti-antibody from other antiglobulins, e.g. rheumatoid factor (RF), and to search their localization of epitope on IgG molecule.

Methods: We chose purified human IgG anti-dsDNA antibody from a patient with systemic lupus erythematosus as IgG antibody and calf thymus dsDNA as antigen. IgG F (ab')₂ fragment was obtained by digestion of the IgG with pepsin. Those IgG and IgG F (ab') 2 with anti-dsDNA antibody were reacted with pre-coated dsDNA and formed immune complex on ELISA plate. On the other hand we prepared ELISA plate on which those IgG and IgG F (ab') 2 were coated directly for measurement of IgM RF and IgM antihinge antibody. Twenty-three sera from patients with rheumatoid arthritis were tested.

Results: Correct IgM anti-antibodies were obtained after subtraction of absorbance of IgM anti-dsDNA anti- bodies. Remarkable correlation between IgM anti-antibodies obtained by using whole IgG and those by using IgG F(ab')₂(n=23, r²=0.914, p=1.11X10-12). There were correlations neither between IgM antiantibodies and IgM RF(n=23, r²=0.001, p=0.889) nor between IgM antiantibodies and IgM antihinge antibodies (n=23, r²=0.063, p=0.249).

Conclusions: IgM molecule with anti-antibody specificity seems to be different from IgM RF and IgM antihinge antibody. Moreover, epitope recognized by IgM anti-antibody seems to localize on IgG F (ab') 2 but not on hinge region. [Original].

The topic of this symposium "advancement of biomarkers" focused on biomarkers and laboratory medicine. The following 4 papers were presented: 1. Liver disease diagnoses and new biomarkers, 2. Atherosclerosis and new biomarkers, 3. Leukemia biomarkers, and 4. A new inhibitory factor against erythropoietin for diagnosis and assessment of anemia. As these titles suggest, this symposium covered broad fields of medical practice. All presentations demonstrated the marked development of new biomarkers in association with advanced technology along with improved understanding of disease pathologies. These frontier research areas related to biomarkers lead to the expectation of further novel practical biomarkers in the future. Further explora- tion in all fields for biomarker development will be performed, leading to new clinically practical diagnostic tools. Laboratory medicine will further contribute through the development of novel diagnostic technologies. [Review].

Patients with disseminated intravascular coagulation (DIC) exhibit increased levels of fibrin/fibrinogen degradation products (FDP), and FDP levels are carefully monitored as a marker of fibrinolysis during the diagnosis of DIC and other fibrinolysis-related conditions. Although FDP levels can be measured using automatic analyzers, it is reported that measured FDP values differ depending on the reagent used. Recently, a newly developed reagent for measuring FDP levels (Lias Auto P-FDP) was launched. In this study, we used Lias Auto P-FDP in combination with the Coapresta 2000 automatic analyzer and evaluated its reactivity. We confirmed the reproducibility of the measurements obtained with the Lias Auto P-FDP reagent when the manufacturer's instructions were followed and that the Lias Auto P-FDP reagent can be used with the Coapresta 2000. In the reactivity test, the Lias Auto P-FDP reagent exhibited stronger reactivity with low molecular weight FDP than the reagent we currently use (BL2 P-FDP). Moreover, the samples that exhibited non-specific reactions to the BL2 P-FDP reagent did not display similar reactions to the Lias auto P-FDP reagent. In the clinico-pathological analysis of divergent value between Lias Auto P-FDP and BL2 P-FDP, seven cases were highly discrepant value of FDP. Interestingly, we found the description of pleural fluid and/or ascites in 85.7% cases. In conclusion, we confirmed that the Lias Auto P-FDP reagent can be used in combination with the Coapresta 2000. In addition, the reactivity of FDP varied depending on the reagent used. It is important to understand the characteristics of each FDP reagent and which automatic analyzers they can be used with. [Original].

Whole-slide imaging (WSI) technology enables the primary diagnosis of histopathological slides. This study aimed to determine the diagnostic concordance between pathological interpretations made using WSI and those made using light microscopy (LM). For this study, 5,704 consecutive surgical pathological cases from a community hospital were included. The specimens were digitized at x40 magnification for biopsy and endoscopic resection specimens or at x20 magnification for other specimens and evaluated by 11 pathologists for diagnosis using WSI. Subsequently, the specimens were signed out using LM by 3 pathologists after 2 weeks. Diagnoses using WSI were then compared with the diagnoses made by using LM. Most (96.8%) of the 5,704 specimens were obtained from the gastrointestinal tract (2,441 biopsy specimens from the esophagogastroduodenum [42.7%], 1,678 endoscopic resection specimens from the colorectum [29.4%], 1,349 biopsy specimens from the colorectum [23.6%], 133 resected specimens from the gallbladder [2.3%], 56 endoscopic resection specimens from the stomach [0.9%], 30 resected specimens from the ap- pendix [0.5%], 14 skin biopsy specimens [0.2%], and 3 other specimens [0.1%]). The overall concordance between the diagnoses made using WSI and those made using LM was 95.1%. The major and minor dis- crepancy rates for WSI were 0.1% and 4.8%, respectively. None of the discordant cases had any clinical or prognostic implications. In conclusion, this study revealed that WSI can be used for primary diagnosis of gastrointestinal biopsy and endoscopic resection specimens. To the best of our knowledge, this is one of the studies that clearly proved that diagnosis using WSI is equivalent to diagnosis using LM. [Original].

The majority of patients with acute promyelocytic leukemia (APL) harbor the t (15;17) (q22;q12) transloca- tion, which results in the expression of PML-RARA mRNA. All-trans retinoic acid (ATRA) is a representa- tive molecular-targeted drug and is directed against PML-RARA. Therefore, the detection of PML-RARA mRNA has become indispensable for the diagnosis of APL and the decision regarding the treatment policy. Once the diagnosis is confirmed by genetic testing, ATRA-based induction therapy can be initiated. This is also applicable in atypical cases such as the M3 variant. Furthermore, after ATRA-based induction therapy, the curative effect is evaluated by quantitative PCR analysis. Thus, genetic testing is important in the follow-up of patients with APL. [Review].