Purpose
Ocular sarcoidosis is diagnosed based on suggestive intraocular findings and systemic investigations. In this study, we assessed the clinical usefulness of systemic parameters in the ...diagnosis of ocular sarcoidosis.
Study design
A retrospective study.
Methods
This study included 79 cases (19 men, 60 women) with ocular sarcoidosis who visited Hokkaido University Hospital from 2011 to 2015 and were followed up for more than one year. The control group was 91 cases of other uveitis (38 men, 53 women). All cases underwent blood examination for the measurement of angiotensin-converting enzyme (ACE), Krebs von den Lungen-6 (KL-6), soluble interleukin-2 receptor (sIL-2R), and calcium (Ca) levels. Bilateral hilar lymphadenopathy (BHL) was also examined by plain chest X-ray and contrasting chest computed tomography (CT).
Results
The sensitivity for sIL-2R (76.4%) was higher than for ACE (37.7%), KL-6 (26.3%), and Ca (11.8%), although all showed high specificity: ACE (97.5%), KL-6 (96.2%), sIL-2R (93.8%), and Ca (95.1%). From these results, the Youden index of sIL-2R (0.70) was higher than that of ACE (0.35), KL-6 (0.26), and Ca (0.07). Imaging tests revealed better detection of BHL by contrasting chest CT (82.7%) than by plain chest X-ray (29.5%).
Conclusion
The present findings indicate that the systemic parameters, particularly serum sIL-2R levels and BHL on contrasting chest CT, are useful biomarkers for the diagnosis of ocular sarcoidosis.
Purpose
Cytomegalovirus (CMV) antigenemia assays have been widely used as adjunct tests to diagnose tissue invasive CMV diseases, including cytomegalovirus retinitis (CMVR). In this study, we ...examined CMVR cases to assess the presence of CMV in sera and aqueous humor and antiviral therapy received prior to the onset of CMVR.
Methods
A total of 37 eyes from 26 different cases of CMVR in patients who visited Hokkaido University Hospital between 2007 and 2015 were enrolled. The diagnosis of CMVR was established based on characteristic ophthalmoscopic findings and the presence of local and/or systemic CMV infection. Among the 26 cases, 3 cases (12%) were HIV-positive, while the other 23 cases (88%) were HIV-negative. The records of clinical and laboratory results were reviewed from clinical charts retrospectively.
Results
CMV antigenemia was positive at the onset of CMVR in 14 cases (53.8%) and negative in the other 12 cases. In 9 cases among the antigenemia-negative cases (75.0%), the antigenemia had been previously positive and had turned negative before the onset of CMVR. In 12 of the 14 antigenemia-positive cases (85.7%) and in 8 of the 9 antigenemia-negative cases (88.9%) that were previously positive, systemic antiviral therapies had never been used or had been used before but had been discontinued prior to the onset of CMVR.
Conclusion
Even if viremia turns negative, the risk of developing CMVR exists for more than several weeks after the completion of systemic therapy.
Mucosal-associated invariant T (MAIT) cells are a unique subset of T cells that recognizes metabolites derived from the vitamin B2 biosynthetic pathway. Since the identification of cognate antigens ...for MAIT cells, knowledge of the functions of MAIT cells in cancer, autoimmunity, and infectious diseases has been rapidly expanding. Recently, MAIT cells have been found to contribute to visual protection against autoimmunity in the eye. The protective functions of MAIT cells are induced by T-cell receptor (TCR)-mediated activation. However, the underlying mechanisms remain unclear. Thus, this mini-review aims to discuss our findings and the complexity of MAIT cell-mediated immune regulation in the eye.
Human parvovirus B19 (B19) infects human erythroid cells expressing P antigen. However, some cell lines that were positive for P antigen failed to bind B19, whereas some cell lines had an ability to ...bind B19 despite undetectable expression of P antigen. We here demonstrate that B19 specifically binds with Ku80 autoantigen on the cell surface. Furthermore, transfection of HeLa cells with the gene of Ku80 enabled the binding of B19 and allowed its entry into cells. Moreover, reduction of cell-surface expression of Ku80 in KU812Ep6 cells, which was a high-sensitive cell line for B19 infection, by short interfering RNA for Ku80 resulted in the marked inhibition of B19 binding in KU812Ep6 cells. Although Ku80 originally has been described as a nuclear protein, human bone marrow erythroid cells with glycophorin A or CD36, B cells with CD20, or T cells with CD3 were all positive for cell-surface expression of Ku80. B19 infection of KU812Ep6 cells and bone marrow cells was inhibited in the presence of anti-Ku80 antibody. Our data suggest that Ku80 functions as a novel coreceptor for B19 infection, and this finding may provide an explanation for the pathologic immunity associated with B19 infection.
Purpose
To determine the factors that may affect the accuracy of vitrectomy cell block technique in detecting atypical lymphoid cells in patients with vitreoretinal lymphoma (VRL).
Methods
We ...retrospectively reviewed 43 eyes in 39 patients who underwent vitrectomy for definitive histological diagnosis of VRL with vitrectomy cell block technique and/or smear preparation at Kyushu University Hospital from January 2001 to March 2016. The association of detection of atypical lymphoid cells using vitrectomy cell block technique with the following factors was assessed using logistic regression analysis: age at diagnosis, sex, presence or absence of concurrent cataract surgery with vitrectomy, clinical grading of vitreous haze, presence or absence of subretinal tumor infiltration, interval between initial symptoms and vitrectomy, and presence or absence of systemic corticosteroid therapy before vitrectomy.
Results
Atypical lymphoid cells were more significantly detected using vitrectomy cell block technique compared to that using smear preparation (
p
= 0.018). After adjusting for age and sex, concurrent cataract surgery (odds ratio OR, 10.41; 95% confidence interval CI, 1.42–76.41) and subretinal tumor infiltration (OR, 5.06; 95% CI, 1.06–24.32) were significantly associated with failure of histological analysis with vitrectomy cell blocks. In multivariable logistic regression analysis, similar results were obtained, although subretinal tumor infiltration was only marginally associated with the detective capability of the technique.
Conclusion
Vitrectomy cell block technique significantly improved the definitive diagnosis of VRL. Concurrent cataract surgery with vitrectomy and subretinal tumor infiltration were risk factors for failure in vitrectomy cell blocks.
Vogt-Koyanagi-Harada (VKH) disease is a systemic inflammatory disorder that affects pigment cell-containing organs such as the eye (e.g., chronic and/or recurrent granulomatous panuveitis). While the ...exact etiology and pathogenic mechanism of VKH disease are unclear, HLA-DR4 alleles have been documented to be strongly associated with VKH disease in various ethnic groups. Recently, a genome-wide association study (GWAS) found two new genetic risk factors (IL23R-C1orf141 and ADO-ZNF365-EGR2) in a non-HLA region from a Han Chinese population. In this study, we replicated these GWAS findings in a Japanese population. A total of 1,643 Japanese samples (380 cases with VKH disease and 1,263 healthy controls) were recruited. We assessed four single nucleotide polymorphisms (SNPs) shown in previous GWAS: rs78377598 and rs117633859 in IL23R-C1orf141, and rs442309 and rs224058 in ADO-ZNF365-EGR2. A significant allelic association with VKH disease was observed for all of the four SNPs (rs78377598: pc = 0.0057; rs117633859: pc = 0.0017; rs442309: pc = 0.021; rs224058: pc = 0.035). In genotypic association analysis, the minor alleles of IL23R-C1orf141 rs78377598 and rs117633859 had the strongest association with disease susceptibility under the additive model (pc = 0.0075 and pc = 0.0026, respectively). The minor alleles of ADO-ZNF365-EGR2 rs442309 and rs224058 were most strongly associated with disease susceptibility under the dominant model (pc = 0.00099 and pc = 0.0023, respectively). The meta-analysis of the current and previous studies found that all of the four SNPs exhibited a significantly strong association with VKH disease (meta-p < 0.00001: rs78377598, meta-odds ratio (OR) = 1.69; rs1176338, meta-OR = 1.82; rs442309, meta-OR = 1.34; rs224058, meta-OR = 1.33). In summary, our study replicated significant associations with VKH disease susceptibility reported in a previous GWAS. Thus, the IL23R-C1orf141 and ADO-ZNF365-EGR2 loci may play important roles in the development of VKH disease through genetic polymorphisms.
Background
Presently, hormonal therapy targeting estrogen receptors is the most effective treatment available for luminal breast cancer. However, many patients relapse after the therapy. It has been ...suggested that cancer stem-like cells are involved with hormonal therapy resistance; in the present study, we evaluated this hypothesis.
Methods
In the present study, we used our previously established hormonal therapy-resistant cell lines, including aromatase inhibitor (AI)-resistant cells (Type 1 and Type 2) and fulvestrant-resistant cells (MFR).
Results
AI-resistant cell lines expressing ER (Type 1 V1 and V2) showed high cancer stemness in terms of their CD44/CD24 expression and side populations, which were stimulated by the addition of estrogen and inhibited by fulvestrant. However, ALDH activity was lower than in the ER-negative resistant cells, suggesting that the stemness of luminal cells is distinct from that of basal-like breast cancer cells. The migration and invasion activity of the ER-positive Type 1 V1 and V2 cells were higher than in the ER-negative cell lines, Type 2 and MFR.
Conclusions
Fractionation of parental cells based on CD44/CD24 expression and colony formation assay indicated that CD44+/CD24+ cells might be the origin of hormonal therapy-resistant cells. This population reconstituted various other subpopulations under estrogen deprivation. These results indicate that hormonal therapy resistance is closely related to the cancer stem cell-like properties of luminal breast cancer.
Multiple myeloma is the cancer of plasma cells. Along with the development of new and effective therapies, improved outcomes in patients with multiple myeloma have increased the interest in minimal ...residual disease (MRD) monitoring. However, the considerable heterogeneity of immunophenotypic and molecular markers of myeloma cells has limited its clinical application. 5-Aminolevulinic acid (ALA) is a natural compound in the heme biosynthesis pathway. Following ALA treatment, tumor cells preferentially accumulate porphyrins because of the differential activities of aerobic glycolysis, known as Warburg effect. Among various porphyrins, protoporphyrine IX is a strong photosensitizer; thus, ALA-based photodynamic diagnosis has been widely used in various solid cancers. Here, the feasibility of flow cytometry-based photodynamic detection of MRD was tested in multiple myeloma. Among various human cell lines of hematological malignancies, including K562 erythroleukemia, Jurkat T-cell leukemia, Nalm6 pre-B cell leukemia, KG1a myeloid leukemia, and U937 monocytic leukemia, human myeloma cell line, KMS18, and OPM2 abundantly expressed ALA transporters, such as SLC36A1 and SLC15A2, and 1 mM ALA treatment for 24 h resulted in nearly 100% porphyrin fluorescence expression, which could be competitively inhibited by ALA transport with gamma-aminobutyric acid. Titration studies revealed that the lowest ALA concentration required to achieve nearly 100% porphyrin fluorescence in KMS18 cells was 0.25 mM, with an incubation period of 2 h. Under these conditions, incubation of primary peripheral blood mononuclear cells resulted in only 1.8 % of the cells exhibiting porphyrin fluorescence. Therefore, flow cytometry-based photodynamic diagnosis is a promising approach for detecting MRD in multiple myeloma.
Individuals are likely to be involved in at least one motor vehicle accident (MVA) during their lifetime. MVAs can have a significant impact on both the victims and their families; in the case of ...death, the bereaved family may face mental health problems. Ongoing studies have focused on devising strategies to support victims and their families who face such problems.
This paper clarifies the reality of mental health issues of MVA victims and reviews the current state of victim support available in Japan, its significance and other relevant issues.
The prevalence of post-traumatic stress disorder (PTSD) in MVA survivors has been estimated to be 8%–45% one month after the accident and 6%–40% six months after the accident. The mental health of the survivors' families, bereaved families, and orphaned children are usually affected after MVAs. Bereaved families experience not only PTSD but also symptoms of complicated grief. Based on studies using different scales to measure symptoms and other items, symptoms of PTSD and complicated grief have been seen in 17%–75% and 6%–61% of bereaved families, respectively, which were much higher than those observed in the general population. In addition to the actual physical and mental damage caused by MVAs, it is necessary to take notice of survivors who are exposed to post-accident secondary victimization.
Justice agencies, such as the National Police Agency and Ministry of Justice Investigation Bureau, as well as victim support centers and self-help groups, provide support to MVA victims. To a certain extent, evaluating support provided to MVA victims and their families is possible by initiating assistance promptly and actively using leaflets, brochures, and other materials.
The literature reports that women are at increased risk for developing PTSD and complicated grief; also, men and women use different mechanisms for coping with stress. Moreover, men tend not to express their pain and try to manage it on their own. Thus, support that is appropriate for both sexes must be provided.
In the future, the effectiveness of the support provided should be evaluated by survivors. Whether acute-phase support leads to improvement in survivors' long-term prognoses must also be investigated.
•Motor vehicle accidents (MVA) reportedly have an impact on the victim's mental health.•This study reviews such impact and the type of support available in Japan for victims.•Bereaved families experience post-traumatic stress disorder and complicated grief.•Support appropriate for victims of both sexes must be provided.•Evaluating support provided to MVA victims and their families is possible by initiating assistance immediately.
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