Group 2 innate lymphoid cells support hematopoietic recovery under stress conditions

The cell-cycle status of hematopoietic stem and progenitor cells (HSPCs) becomes activated following chemotherapy-induced stress, promoting bone marrow (BM) regeneration; however, the underlying molecular mechanism remains elusive. Here we show that BM-resident group 2 innate lymphoid cells (ILC2s) support the recovery of HSPCs from 5-fluorouracil (5-FU)–induced stress by secreting granulocyte-macrophage colony-stimulating factor (GM-CSF). Mechanistically, IL-33 released from chemo-sensitive B cell progenitors activates MyD88-mediated secretion of GM-CSF in ILC2, suggesting the existence of a B cell–ILC2 axis for maintaining hematopoietic homeostasis. GM-CSF knockout mice treated with 5-FU showed severe loss of myeloid lineage cells, causing lethality, which was rescued by transferring BM ILC2s from wild-type mice. Further, the adoptive transfer of ILC2s to 5-FU–treated mice accelerates hematopoietic recovery, while the reduction of ILC2s results in the opposite effect. Thus, ILC2s may function by “sensing” the damaged BM spaces and subsequently support hematopoietic recovery under stress conditions.     

Viable herpes simplex virus type 1 and varicella‐zoster virus in the trigeminal ganglia of human cadavers

Human herpes simplex virus type 1 (HSV‐1) and varicella‐zoster virus (VZV) were isolated in the bilateral trigeminal ganglia of 12 human cadavers with no history of herpes‐related symptoms within 1–5 days of death. Sixteen trigeminal ganglia were subjected to explant culture by using Vero cells, but no cytopathogenic effects (CPE) were observed. However, when another eight trigeminal ganglia were placed in a cell strainer and kept from direct contact with Vero cells during culture, CPE were clearly apparent in all cultures. The amount of DNA in the culture supernatants of 16 trigeminal ganglia decreased over time; 12 and 9 of these samples were PCR‐positive for HSV‐1 and VZV, respectively. In new Vero cells inoculated with supernatants collected 2 days after culture initiation, immunofluorescence staining revealed HSV‐1 and VZV in 6 and 5 of 8 trigeminal ganglia, respectively. HSV‐1 and VZV DNA was detected in supernatants collected 3 and 7 days after culture initiation and in Vero cells collected after culture completion, but real‐time PCR revealed the DNA amounts decreased over time. There was less VZV DNA than HSV‐1 DNA. These results demonstrate that infective HSV‐1 and VZV can be isolated in culture, and confirm that viable HSV‐1 and VZV persist in human trigeminal ganglia for some time after death. J. Med. Virol. 85:833–838, 2013. © 2013 Wiley Periodicals, Inc.     

Relationship Between Motor Function,DTI, and Neurophysiological Parameters in Patients with Stroke in the Recovery Rehabilitation unit

ObjectivesWe investigated the relationship between pyramidal tract evaluation indexes (i.e., diffusion tensor imaging, transcranial magnetic stimulation (TMS)-induced motor-evoked potential (MEP), and central motor conduction time (CMCT) on admission to the recovery rehabilitation unit) and motor functions at discharge in patients with ischemic or hemorrhagic stroke.Materials and MethodsSeventeen patients were recruited (12 men; 57.9 ± 10.3 years). The mean fractional anisotropy (FA) values of the right and left posterior limbs of the internal capsule were estimated using a computer-automated method. We determined the ratios of FA values in the affected and unaffected hemispheres (rFA), TMS-induced MEP, and the ratios of CMCT in the affected and unaffected hemispheres (rCMCT) and examined their association with motor functions (Fugl–Meyer Assessment (FMA) and Action Research Arm Test (ARAT)) at discharge.ResultsHigher rFA values of the posterior limb of the internal capsule on admission to the recovery rehabilitation unit led to a better recovery of upper limb function (FMA: r = 0.78, p < 0.001; ARAT: r = 0.74, p = 0.001). Patients without MEP had poorer recovery of upper limb function than those with MEP (FMA: p < 0.001; ARAT: p = 0.001). The higher the rCMCT, the poorer the recovery of upper limb function (ARAT: r = ?0.93, p < 0.001). However, no association was observed between the pyramidal tract evaluation indexes and recovery of lower limb motor function.ConclusionsEvaluating the pyramidal tract is useful for predicting upper limb function prognosis, but not for lower limb function prognosis.     

Robustness of a Combined Modified Dixon and PROPELLER Sequence with Two Interleaved Echoes in Clinical Head and Neck MRI

Purpose:The combination of modified Dixon (mDixon) and periodically rotated overlapping parallel lines with enhanced reconstruction sequence with two interleaved echoes, which promotes uniform fat-suppression and motion insensitivity, has recently become available for commercial magnetic resonance imaging (MRI) scanners. To compare the robustness of this combination sequence with that of standard Cartesian mDixon sequence for fat-suppressed T₂-weighted imaging in clinical head and neck MRI.Methods:Fifty patients with head and neck tumors were involved this study. All patients underwent MRI using both the combination and standard sequences. Two radiologists independently scored motion artifacts and water–fat separation error using a 4-point scale (1, unacceptable; 4, excellent). Furthermore, comprehensive comparative evaluation was performed using a 5-point scale (1, substantially inferior; 5, substantially superior). Data were statistically analyzed using the Wilcoxon signed-rank test.Results:In the motion artifact assessment, ratings of 3 or 4 points were assigned to 45% (observer-1, 58.0%; observer-2, 32.0%) and 97% (100%; 94.0%) of images for the standard and combination sequences, respectively (P < 0.001). For the water–fat separation error assessment, ratings of 3 or 4 points were assigned to 100% (100%; 100%) and 85% (84.0%; 86.0%) of images, respectively (P < 0.001). In the comprehensive evaluation, of the 100 cases (observer-1, 50; observer-2, 50), 96 were rated at four or five points. In cases with slight or no motion artifacts and water–fat separation errors, the combination sequence was superior to the standard sequence in term of noise and sharpness, and equal in terms of contrast.Conclusion:Although water–fat separation errors increased significantly in the combination sequence, most of these were acceptable. The significantly decreased motion artifacts in the combination sequence significantly improved image quality overall.     

A national surveillance study of the current status of reirradiation using brachytherapy in Japan

PurposeThis study aimed to explore the current status and pattern of practice for reirradiation using brachytherapy (ReRT-BT) through a survey in Japan.Materials and MethodsWe distributed an e-mail-based questionnaire to 153 institutions equipped with high-dose-rate brachytherapy facilities.ResultsWe received responses from 76 institutions (49.7%). Forty-three of these institutions performed ReRT-BT and 42 institutions (55%) performed ReRT-BT during 2009–2018. However, 29 of the 42 institutions (69%) reported difficulty in obtaining ReRT-BT case information from their respective databases. Almost all the institutions encountered insufficient database system to extract details about the ReRT-BT cases. Responses from 33 institutions included the number of ReRT-BT cases; this increased from 90 in the period 2009–2013 (institution median = 0.5; 0–16) to 172 in the period 2014–2018 (institution median = 2; 0–26). Nine institutions had to perform ReRT-BT for more than one case per year. The major location for cancer treatment was the pelvis (94%), followed by the head and neck (5%) and others (1%). In six site-specific scenarios, barring uterine corpus cancer recurrence, more than 90% of radiation oncologists agreed to perform ReRT-BT, whereas other areas (head and neck, prostate, and rectal cancer) gained 16–37% agreement.ConclusionsThis decade saw an increase in the number of ReRT-BT cases in Japan and radiation oncologists’ interest in ReRT-BT as a viable therapeutic option. However, scarce availability, immature education system, and insufficient database system are barriers to further consensus building.     

Peripheral nerves are involved in hypomyelinating leukodystrophy-3 caused by a homozygous AIMP1 variant

IntroductionAminoacyl-tRNA synthetase-interacting multifunctional protein 1 (AIMP1) is a non-catalytic component of the multi-tRNA synthetase complex that catalyzes the ligation of amino acids to their correct tRNAs. Bi-allelic truncating variants in the AIMP1 gene have been associated with hypomyelinating leukodystrophy-3 (HLD3; MIM 260600), which is characterized by hypomyelination, microcephaly, seizures and decreased life expectancy. Although peripheral nerve involvement has been assumed for HLD3, no compelling evidence is available to date.Case reportThe case was a first-born Filipino male. He showed profound developmental delay, failure to thrive, and spasticity in his limbs. At three months of age he developed refractory epilepsy. Serial magnetic resonance imaging (MRIs) showed profound myelination delay and progressive cerebral atrophy. He showed abnormal nerve conduction studies. Genetic testing revealed a homozygous pathogenic variant in the AIMP1 gene (NM_004757.3: c.115C > T: p.Gln39*). The parents were heterozygous for the same variant.ConclusionHere, we report a patient with a homozygous nonsense AIMP1 variant showing peripheral neuropathy as well as HLD3. Our case suggests that AIMP1 plays a pivotal role in the peripheral nerve as well as the central nervous system.     

Transient hypoglycorrhachia with paroxysmal abnormal eye movement in early infancy

Paroxysmal abnormal eye movement in early infancy is one of the initial symptoms of glucose transporter 1 deficiency syndrome (GLUT1DS). We describe four early infants with transient hypoglycorrhachia presenting with abnormal eye movements. Their symptoms disappeared after the introduction of a ketogenic diet (KD), and their development was normal. Since no variants in SLC2A1 were detected, the CSF-to-blood glucose ratios (C/B) were re-examined, and within normal range. None of the four patients displayed recurrent symptoms after withdrawal from the KD. Because long-term KD has potential adverse effects and could affect the quality of life of patients and their families, re-examination of CSF glucose during late infancy should be considered in the case of absence of the SLC2A1 pathogenic variant.     

Low-dose Interferon-α Treatment Improves Survival and Inflammatory Responses in a Mouse Model of Fulminant Acute Respiratory Distress Syndrome

Acute respiratory distress syndrome (ARDS) is accompanied by severe lung inflammation induced by various diseases. Despite the severity of symptoms, therapeutic strategies for this pathologic condition are still poorly developed. Interferon (IFN)-α is well known as an antiviral cytokine and low-dose IFN-α has been reported to show antiinflammatory effects. Therefore, we investigated how this cytokine affected ARDS in a mouse model. C57BL/6 mice received sequential intratracheal administration of α-galactosylceramide (α-GalCer) and lipopolysaccharide (LPS), which resulted in the development of fulminant ARDS. These mice were then treated intranasally with IFN-α and their survival, lung weight, pathological findings, and cytokine production were evaluated. Administration of low-dose IFN-α prolonged survival of fulminant ARDS mice, but higher doses of IFN-α did not. Histological analysis showed that low-dose IFN-α treatment improved findings of diffuse alveolar damage in fulminant ARDS mice, which was associated with reduction in the wet/dry (W/D) lung weight ratio. Furthermore, IFN-γ production in the lungs was significantly reduced in IFN-α-treated mice, compared with control mice, but tumor necrosis factor (TNF)-α production was almost equivalent for both groups. Low-dose IFN-α shows antiinflammatory and therapeutic effects in a mouse model of fulminant ARDS, and reduced production of IFN-γ in the lung may be involved in the beneficial effect of this treatment.