A Paced Auditory Serial Addition Task evokes stress and differential effects on masseter-muscle activity and haemodynamics

This study aimed to determine autonomic and jaw-muscle activities, and haemodynamic responses, to acute experimental mental stress in humans. Eleven healthy men (25.2 ± 3.0 years of age) and five healthy women (23.0 ± 3.7 years of age) performed a standardized mental stress task, the Paced Auditory Serial Addition Task (PASAT). Autonomic function, such as heart rate variability (HRV), and haemodynamic changes were recorded simultaneously. The success rate of the PASAT decreased with increased pace and duration. Low-frequency (5.8 ± 1.1 ms(2)) and high-frequency (5.3 ± 0.6 ms(2)) components of HRV decreased during the PASAT (to 5.0 ± 0.9 ms(2) and 4.6 ± 1.1 ms(2), respectively) as an indication of acute stress. Oxygenated haemoglobin in the masseter muscle (14.6 ± 2.2 10(4) units mm(-3)) remained at an elevated level during the PASAT (15.5 ± 2.5 10(4) units mm(-3)), whereas deoxygenated haemoglobin (7.8 ± 2.3 10(4) units mm(-3)) showed a consistent decrease (to 6.8 ± 2.1 10(4) units mm(-3)). Total haemoglobin and jaw-muscle electromyographic (EMG) activity did not change during the PASAT. Thus, PASAT-induced mental stress changed the parasympathetic/sympathetic balance of the heart and had an acute influence on jaw-muscle haemodynamics, but not on jaw-muscle EMG activity. This non-invasive experimental set-up can be applied to study the effects of repeated or longer-lasting mental stress in order to further the understanding of pathophysiological mechanisms in craniofacial pain conditions.     

Survey on examinations for diagnosis of bone marrow failure in Japan: a report from the Japanese National Research Group on Idiopathic Bone Marrow Failure Syndromes

Using a registration sheet of a prospective registration system for aplastic anemia (AA)/myelodysplastic syndromes (MDS), by the National Research Group on Idiopathic Bone Marrow Failure Syndromes, Japan, we carried out a survey on examinations for diagnosis of bone marrow failure. Bone marrow trephine biopsy was performed in 66 of 105 cases (63%) [Original diagnosis: AA 51 cases (80%), MDS 12 (32%), undiagnosable 3 (75%)]. Bone marrow aspiration was performed in all cases, and aspiration was performed at least twice in 36 cases (34%). The first-line anatomic site for bone marrow aspiration was the posterior iliac crest (62%). Cytogenetic examination was performed in 93%. The concordance rate between the original and the central review diagnosis was 93% among the studied cases: AA, Idiopathic cytopenia of undetermined significance (ICUS) and MDS in total. Flow cytometry analysis to detect paroxysmal nocturnal hemoglobinuria (PNH)-type blood cells was performed in 32%.     

Successful treatment of a chronic-phase T-315I-mutated chronic myelogenous leukemia patient with a combination of imatinib and interferon-alfa

The T315I BCR-ABL mutation in chronic myelogenous leukemia (CML) patients is responsible for up to 20% of all clinically observed resistance. This mutation confers resistance not only to imatinib, but also to second-generation BCR-ABL tyrosine kinases, such as nilotinib and dasatinib. A number of strategies have been implemented to overcome this resistance, but allogeneic stem cell transplantation remains the only established therapeutic option for a cure. A 61-year-old male was diagnosed with Philadelphia chromosome-positive chronic-phase CML in 2002. He was initially treated with imatinib and complete cytogenetic response (CCyR) was achieved 12 months later. However, after 18 months, a loss of CCyR was observed and a molecular study at 24 months revealed a T315I mutation of the BCR-ABL gene. At 30 months, imatinib/interferon-alfa (IFNα) combination therapy was initiated in an effort to overcome the resistance. Thirty months later, he re-achieved CCyR, and the T315I BCR-ABL mutation disappeared at 51 months. To our knowledge, this is the first case report showing the effectiveness of imatinib/IFNα combination therapy for CML patients bearing the T315I BCR-ABL mutation.     

A case of naturally occurring visual field loss in a chimpanzee with an arachnoid cyst

Deficits in the occipital cortex have varying consequences among mammalian species. Such variations are indicative of evolutionary transitions in the striate cortical contribution to visually guided behavior. However, little is known about the role of the striate cortex in visually guided behavior in chimpanzees due to ethical concerns about invasive experiments and methodological limitations such as the inability to monitor gaze movements. We had the opportunity to study the behavioral consequences of a deficit in the occipital cortex in a chimpanzee with a naturally occurring arachnoid cyst in her right occipital lobe. We assessed the chimpanzee's ability to detect a small light probe (0.5 visual degree, Michelson contrast>0.9) presented at several locations in the visual field while monitoring gaze direction using an infra-red remote eye-tracker recently introduced to studies of great apes. The results showed the chimpanzee was unable to detect the probe in the lower left quadrant of the visual field, suggesting severe loss of contrast sensitivity in a part of hemivisual field that is retinotopically corresponded to the hemisphere of the cyst. A chimpanzee with a naturally occurring deficit in the right striate cortex and the availability of remote eye-tracking technology presented a unique opportunity to compare the role of the occipital lobe in visually guided behavior among various primate species.     

Effects of 3,3',5‐triiodothyronine on microglial functions

l ‐tri‐iodothyronine (3, 3', 5–triiodothyronine; T3) is an active form of the thyroid hormone (TH) essential for the development and function of the CNS. Though nongenomic effect of TH, its plasma membrane–bound receptor, and its signaling has been identified, precise function in each cell type of the CNS remained to be investigated. Clearance of cell debris and apoptotic cells by microglia phagocytosis is a critical step for the restoration of damaged neuron‐glia networks. Here we report nongenomic effects of T3 on microglial functions. Exposure to T3 increased migration, membrane ruffling and phagocytosis of primary cultured mouse microglia. Injection of T3 together with stab wound attracted more microglia to the lesion site in vivo. Blocking TH transporters and receptors (TRs) or TRα‐knock‐out (KO) suppressed T3‐induced microglial migration and morphological change. The T3‐induced microglial migration or membrane ruffling was attenuated by inhibiting G_i/o‐protein as well as NO synthase, and subsequent signaling such as phosphoinositide 3‐kinase (PI3K), mitogen‐activated protein kinase (MAPK)/extracellular signal‐regulated kinase (ERK). Inhibitors for Na⁺/K⁺‐ATPase, reverse mode of Na⁺/Ca²⁺ exchanger (NCX), and small‐conductance Ca²⁺‐dependent K⁺ (SK) channel also attenuated microglial migration or phagocytosis. Interestingly, T3‐induced microglial migration, but not phagocytosis, was dependent on GABA_A and GABA_B receptors, though GABA itself did not affect migratory aptitude. Our results demonstrate that T3 modulates multiple functional responses of microglia via multiple complex mechanisms, which may contribute to physiological and/or pathophysiological functions of the CNS. GLIA 2015:63:906–920     

Comprehensive analysis of the ICEN (Interphase Centromere Complex) components enriched in the CENP-A chromatin of human cells

The centromere is a chromatin structure essential for correct segregation of sister chromatids, and defects in this region often lead to aneuploidy and cancer. We have previously reported purification of the interphase centromere complex (ICEN) from HeLa cells, and have demonstrated the presence of 40 proteins (ICEN1-40), along with CENP-A, -B, -C, -H and hMis6, by proteomic analysis. Here we report analysis of seven ICEN components with unknown function. Centromere localization of EGFP-tagged ICEN22, 24, 32, 33, 36, 37 and 39 was observed in transformant cells. Depletion of each of these proteins by short RNA interference produced abnormal metaphase cells carrying misaligned chromosomes and also produced cells containing aneuploid chromosomes, implying that these ICEN proteins take part in kinetochore functions. Interestingly, in the ICEN22, 32, 33, 37 or 39 siRNA-transfected cells, CENP-H and hMis6 signals disappeared from all the centromeres in abnormal mitotic cells containing misaligned chromosomes. These results suggest that the seven components of the ICEN complex are predominantly localized at the centromeres and are required for kinetochore function perhaps through or not through loading of CENP-H and hMis6 onto the centromere.     

Donor-derived DNA in fingernails among recipients of allogeneic hematopoietic stem-cell transplants

To examine whether donor-derived cells could exist in nonhematopoietic tissues of recipients after allogeneic hematopoietic stem-cell transplantation, we examined the patterns of the short tandem repeat (STR) of DNA extracted from fingernail clippings of recipients so that the contamination of blood cells was excluded. All 21 patients reached donor-derived hematopoiesis after transplantation and 20 of them were in remission of the primary diseases at the time of sampling. Compared with the STRs of donor cells, among 9 of 21 patients, DNA extracted from fingernail samples showed coexistence of the donor pattern of the STRs, sharing from 8.9% to 72.9% of total STR areas. Time from transplantation to sampling was from 305 to 2399 days among positive cases. These results demonstrate for the first time the existence of stable contribution of donor cells in fingernails among recipients of allogeneic hematopoietic stem cells.