White‐matter damage in a neonate with disseminated herpes simplex virus infection

Kojima, Karin; Takahashi, Naoto; Yada, Yukari; Koike, Yasunori; Matano, Miyuki; Kono, Yoshiaki; Momoi, Mariko Y.

doi:10.1111/j.1442-200x.2011.03428.x

Cited by 7 publications

(6 citation statements)

References 13 publications

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“…The aim of HLH treatment is to suppress hyper inflammation. We reported a case of HSV infection with HLH, in which we could control hypercytokinemia with corticosteroids and cyclosporine (Kojima et al 2012). Melvin et al (2015) showed that no infants with plasma HSV concentrations ≤ 1 ×10 7 copies/µL died, and the concentrations of all infants who died were over 1 × 10 7 copies/µL.…”

Section: Discussionmentioning

confidence: 98%

“…It occasionally involves renal failure (Capretti et al 2013), and some neonates need continuous renal replacement therapy (Funaki et al 2015). This disease is sometimes associated with hemophagocytic lymphohistiocytosis (HLH), and anti-cytokine therapy is required (Janka and Schneider 2004;Suzuki et al 2009;Kojima et al 2012). We encountered a neonatal patient with disseminated HSV infection with high viral load and HLH.…”

Section: Introductionmentioning

confidence: 97%

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Critically Severe Case of Neonatal Herpes with High Viral Load and Hemophagocytic Syndrome

Takehara

Hirohata

Mutoh

et al. 2019

Tohoku J. Exp. Med.

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Neonatal disseminated herpes simplex virus (HSV) infection is a severe disease with high mortality and morbidity; yet, the pathophysiology remains unclear. Here, we report a male infant with disseminated HSV type 1 (HSV-1) infection, complicated by hemophagocytic lymphohistiocytosis (HLH) and multiple organ failure. The infant, born at 39 weeks of gestation by normal delivery, developed fever (38.5˚C) with the high serum C-reactive protein levels on the 1st day of life, and exhibited tachypnea on the 3rd day. On the 5th day of life, the patient received mechanical ventilation and was transferred to our neonatal ICU. Real-time PCR for HSV-1 DNA revealed an extremely high serum concentration (1.0 × 10 9 copies/µL), and he was diagnosed with HSV-1 infection. Acyclovir (ACV) and corticosteroid pulse therapies with methylprednisolone were started. Continuous hemodiafiltration (CHDF) using cytokine-absorbing hemofilters was also initiated because of renal failure. These therapies, however, failed to control the disease, and the patient died on the 41st day of life. The dose of ACV on CHDF might not be adequate, although we could not measure the serum ACV concentrations. After the patient's death, we measured his serum cytokine concentrations taken four times during the clinical course. Serum concentrations of interleukin (IL)-6, IL-10, IL-1β, and interferon (IFN)-γ were elevated at the time of admission and were remarkably decreased by 10 days after treatment. In particular, the concentrations of IL-1β and IFN-γ were lower than the measurable ranges. It is therefore important to measure serum cytokine concentrations in real time to prevent excessive immune suppression.

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Section: Discussionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 97%

Critically Severe Case of Neonatal Herpes with High Viral Load and Hemophagocytic Syndrome

Takehara

Hirohata

Mutoh

et al. 2019

Tohoku J. Exp. Med.

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“…The usage of hmDNA as a biomarker for cancer detection is currently limited because it is difficult to distinguish hmDNA from nonmethylated DNA. − Current methods include the use of methylation-sensitive restriction enzymes, − bisulfite conversion, , and affinity purification. − However, the methods can result in DNA degradation upon bisulfite conversion, incomplete digestion when using a restriction enzyme digest, and selectivity issues during affinity purification. , The advantage of affinity purification is that it only involves a molecular recognition binding step followed by an elution step, thus requiring short assay times. Affinity purification of hmDNA is generally used to enrich a solution with hmDNA using beads of which the surfaces are modified with the methyl binding domain-2 (MBD2) protein. ,,, The MBD2 protein is used as a receptor that interacts with a methylated CpG (C*pG, ligand) with a dissociation constant of 3–66 nM. − Furthermore, MBD2 has been demonstrated to have one of the best intrinsic binding selectivities among the proteins present within the MBD protein family, − with dissociation constant values ranging between 188 and 6500 nM for nonmethylated CpG (CpG). , Despite this intrinsic binding selectivity of MBD2 for C*pG, the coenrichment of nonmethylated DNA upon the isolation of hmDNA remains one of the greatest limitations of MBD-based affinity methods. ,,, …”

Section: Introductionmentioning

confidence: 99%

“…13,15−17 The usage of hmDNA as a biomarker for cancer detection is currently limited because it is difficult to distinguish hmDNA from nonmethylated DNA. 18−23 Current methods include the use of methylation-sensitive restriction enzymes, 24−26 bisulfite conversion, 27,28 and affinity purification. 29−31 However, the methods can result in DNA degradation upon bisulfite conversion, incomplete digestion when using a restriction enzyme digest, and selectivity issues during affinity purification.…”

Section: ■ Introductionmentioning

confidence: 99%

Density Control over MBD2 Receptor-Coated Surfaces Provides Superselective Binding of Hypermethylated DNA

Kolkman

Michel-Souzy

Wasserberg

et al. 2022

ACS Appl. Mater. Interfaces

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Using the biomarker hypermethylated DNA (hmDNA) for cancer detection requires a pretreatment to isolate or concentrate hmDNA from nonmethylated DNA. Affinity chromatography using a methyl binding domain-2 (MBD2) protein can be used, but the relatively low enrichment selectivity of MBD2 limits its clinical applicability. Here, we developed a superselective, multivalent, MBD2-coated platform to improve the selectivity of hmDNA enrichment. The multivalent platform employs control over the MBD2 surface receptor density, which is shown to strongly affect the binding of DNA with varying degrees of methylation, improving both the selectivity and the affinity of DNAs with higher numbers of methylation sites. Histidine-10-tagged MBD2 was immobilized on gold surfaces with receptor density control by tuning the amount of nickel nitrilotriacetic acid (NiNTA)-functionalized thiols in a thiol-based self-assembled monolayer. The required MBD2 surface receptor densities for DNA surface binding decreases for DNA with higher degrees of methylation. Both higher degrees of superselectivity and surface coverages were observed upon DNA binding at increasing methylation levels. Adopting the findings of this study into hmDNA enrichment of clinical samples has the potential to become more selective and sensitive than current MBD2-based methods and, therefore, to improve cancer diagnostics.

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“…The second approach to differentiate between the two types of DNA is bisulfite conversion. [31,32] Using this chemical modification method, all non-methylated cytosines are converted into the base uracil, while all methylated cytosines remain unconverted. As a result, the base sequence of the nonmethylated DNA changes, allowing an easier differentiation using PCR.…”

Section: Introductionmentioning

confidence: 99%

Selective Enrichment of Hypermethylated DNA by a Multivalent Binding Platform

Kolkman

Segerink

Huskens

2022

Adv Materials Inter

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One of the key aspects of surviving cancer is to detect the disease as early as possible, thereby enlarging the window of opportunity of curing it. [4,5] A recent trend for early cancer diagnostics is the pre-symptomatic detection of cancer biomarkers in liquid biopsy samples and, therefore, improving the survival rate. [6,7] Hypermethylated DNA (hmDNA) is one of the typical biomarkers found in liquid biopsy samples of cancer patients. [8,9] The presence of hmDNA in blood and urine is correlated to multiple types of cancer, including gastric, lung and ovarian cancer. [10][11][12][13] From a genetic point of view, DNA methylation takes place predominantly at promotor regions with a relative high amount of cytosine bases that are followed directly by a guanine (CpGs) in the 5′-to-3′ direction, the so-called CpG-rich regions. [13] The methylation of a CpG is an epigenetic alternation in which a methyl group is covalently bonded to the cytosine base at the fifth carbon. By CpG methylation, gene expressions are controlled in cells. As a consequence, methylation can play a role in tumor development when tumor suppressor genes are methylated, thereby repressing the transcription and thus silencing these genes. [14] Hypermethylation refers to the situation that methylation of a promotor region occurs, which in a healthy situation does not occur.Early disease detection as well as disease progress and the effectiveness of a therapy can be monitored by measuring the hmDNA concentration over time. [15] Yet, the concentration of hmDNA, especially in early-stage cancers, can be as low as a few DNA copies per liquid biopsy sample. [16][17][18] The current approach to measure hmDNA employs DNA isolation and bisulfite conversion, making it time-consuming and labor intensive. As a result, the method is not widely applicable in the clinic. Typically, hmDNA is detected in bisulfite-treated DNA samples by quantitative polymerase chain reaction (PCR) (qPCR, of the region of interest; can be cancer dependent). Alternative hmDNA detection approaches that may be suitable for use in point-of-care applications, include electrochemistry, [19] CRISPR [20] and isothermal amplification. [21] The detection of specific hmDNA biomarkers by sequencing or biosensing approaches involves the ability to distinguish between hmDNA and non-methylated DNA. [22][23][24] Commonly a preselection step is applied, and three different approaches exist in order to differentiate between hmDNA and non-methylatedThe preselection of hypermethylated DNA (hmDNA) from liquid biopsy samples is key to enable early-stage cancer diagnostics. Due to limited selectivity of the existing preselection approaches, however, wide integration in the clinic is currently prohibited. Here, it is argued that an affinity method on a surface, such as used in affinity chromatography, can be significantly improved by employing the principles of multivalency and superselectivity. In the here proposed method, a methyl binding domain (MBD) protein immobilized at a surface is used as a recepto...

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White‐matter damage in a neonate with disseminated herpes simplex virus infection

Cited by 7 publications

References 13 publications

Critically Severe Case of Neonatal Herpes with High Viral Load and Hemophagocytic Syndrome

Critically Severe Case of Neonatal Herpes with High Viral Load and Hemophagocytic Syndrome

Density Control over MBD2 Receptor-Coated Surfaces Provides Superselective Binding of Hypermethylated DNA

Selective Enrichment of Hypermethylated DNA by a Multivalent Binding Platform

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