Anatomical Variations in Stylopharyngeus Muscle Insertions Suggest Interindividual and Left/Right Differences in Pharyngeal Clearance Function of Elderly Patients: A Cadaveric Study

The stylopharyngeus plays a critical role in the clearance of the piriform recess. We dissected 78 sides of the pharynx from 55 donated cadavers and observed histology of another seven sides of the pharynx from seven cadavers. The stylopharyngeus consistently comprised (1) a descending muscle bundle surrounding the piriform recess and (2) an additional short sheet inserting into the tonsillar bed. Histologically, the former bundle connected to a thick fascia providing the lateral glossoepiglottic fold, extending along the submucosa of the piriform recess, and covering the thyroid cartilage, whereas the latter sheet intermingled with other pharyngeal wall muscles at and near the tonsillar bed. Notably, in 44.4% of female specimens, the additional sheet occupied a greater proportion in cross section than the descending muscle bundle. Given the different directions, the additional sheet seemed to check clearance function of the descending bundle for the piriform recess. Thus, particularly in women, interindividual differences in pharyngeal clearance were likely to depend on whether the additional sheet is strong or weak. Chin down in combination with tilting and rotating the head may represent effective exercises of the stylopharyngeus that could compensate for the disadvantages of additional insertion.     

Aggressive surgical resection for hepatocellular carcinoma with tumor thrombus extending to inferior vena cava and synchronous pulmonary metastasis

We describe a 66-year-old man having hepatocellular carcinoma with tumor thrombus extending into the inferior vena cava and synchronous pulmonary metastasis. He was referred to Chiba University Hospital on May, 2000, complaining of emaciation. Radiological findings showed a huge hepatocellular carcinoma in the entire right lobe and tumor thrombus extended into the intrapericardial inferior vena cava. He also had a solitary pulmonary metastasis in the left pulmonary lobe (stage IVB). Right hemihepatomy was performed under total hepatic vascular exclusion without cardiopulmonary bypass, and tumor thrombus was completely removed. Thoracoscopic wedge resection of pulmonary metastasis was also performed. The patient had an uneventful postoperative course. Histopathological examination revealed that the tumor was moderately differentiated hepatocellular carcinoma The patient is still alive after 26 months with pulmonary recurrence, but without hepatic recurrence. To our knowledge, there has been no reported case of resection for both hepatocellular carcinoma invading the inferior vena cava and synchronous pulmonary metastasis. In conclusion, aggressive surgical resection for advanced hepatocellular carcinoma concomitant with pulmonary resection may bring about better prognosis in highly selected patients.     

Complex interactions between the laminin alpha 4 subunit and integrins regulate endothelial cell behavior in vitro and angiogenesis in vivo

The alpha4 laminin subunit is a component of the basement membrane of blood vessels where it codistributes with the integrins alphavbeta3, alpha3beta1, and alpha6beta1. An antibody against the G domain (residues 919-1207; G(919-1207)) of the alpha4 laminin subunit inhibits angiogenesis in a mouse-human chimeric model, indicating the functional importance of this domain. Additional support for the latter derives from the ability of recombinant G(919-1207) to support endothelial cell adhesion. In particular, endothelial cell adhesion to G(919-1207) is half-maximal at 1.4 nM, whereas residues 919-1018 and 1016-1207 of the G domain are poor cellular ligands. Function blocking antibodies against integrins alphavbeta3 and beta1 and a combination of antibodies against alpha3 and alpha6 integrin subunits inhibit endothelial cell attachment to G(919-1207). Moreover, both alphavbeta3 and alpha3beta1 integrin bind with high affinity to G(919-1207). Together, our studies demonstrate that the G domain of laminin alpha4 chain is a specific, high affinity ligand for the alphavbeta3 and alpha3beta1 integrin heterodimers and that these integrins, together with alpha6beta1, function cooperatively to mediate endothelial cell-alpha4 laminin interaction and hence blood vessel development. We propose a model based on these data that reconcile apparent discrepancies in the recent literature with regard to the role of the alphavbeta3 integrin in angiogenesis.     

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.