The effect of a first-generation H1-antihistamine on postural control: a preliminary study in healthy volunteers

First-generation H₁-antihistamines are known to cause fatigue and drowsiness, due to their poor receptor selectivity and their high penetration rate of the blood–brain barrier. However, little is known about the effects of first-generation H₁-antihistamines on postural stability. The purpose of this study was to evaluate the effects of d-chlorpheniramine on postural stability using posturography with and without foam rubber. A double-blind study with three parallel groups was conducted. Twenty-seven healthy young volunteers (mean age 21.9 years) were recruited and orally administered d-chlorpheniramine, 2 or 4 mg, or placebo. Postural sway was measured every hour up to 8 h after administration. Two-legged stance tasks were performed by each subject in four conditions: eyes open or eyes closed and with or without foam rubber. Inter-group comparisons showed that the group receiving 4-mg d-chlorpheniramine showed significantly larger sway in the eyes open with foam rubber condition (visual and vestibular information available, somatosensory information reduced). Inter-subject analysis in the 4-mg d-chlorpheniramine group showed that the effect of d-chlorpheniramine on postural control was variable. Our results suggest that among the three main sensory systems responsible for postural control (visual, vestibular, and somatosensory), d-chlorpheniramine may have a larger effect on the visual and/or vestibular systems in susceptible individuals.     

In Vitro Analysis of the Functional Effects of an NLRP3 G809S Variant with the co-Existence of MEFV Haplotype Variants in Atypical Autoinflammatory Syndrome

Purpose

Hereditary periodic fever syndromes have been considered monogenic diseases. However, some recent reports have described patients with co-existence of recurrent fever responsible genes. This study assessed whether a rare variant, found in Japanese children showing atypical autoinflammatory syndrome, located in the leucine-rich repeat domain of Nod-like receptor family, pyrin domain containing 3 (NLRP3) with co-existence of Mediterranean fever (MEFV) haplotype variants may contribute to a proinflammatory phenotype using a systematic approach.

Methods

Cytokine production in serum or from peripheral blood monocytes was measured by ELISA. DNA sequence analysis of genes including NLRP3, MEFV, mevalonate kinase (MVK), and tumor necrosis factor receptor superfamily, member 1A (TNFRSF1A) were performed on patient samples. In vitro functional assays determined the effects of the NLRP3 variants and pyrin using NF-κB activation and speck formation assays.

Results

A heterozygous genetic variant of NLRP3, G809S, was found in samples from both patients. Additionally the previously reported heterozygous MEFV variants (P369S-R408Q or E148Q-P369S-R408Q) were also detected in both patients. Serum IL-1ra and sTNFR1 levels increased in the attack phase of the disease in both patients. The production levels of IL-1β from monocytes isolated from both cases were elevated following LPS and IFN-γ stimulation. The NLRP3 G809S variant demonstrated no increase of NF-κB activity following monosodium urate stimulation, whereas it significantly increased speck formation by interacting with apoptosis-associated speck-like protein with caspase recruitment domain.

Conclusions

The phenotype of atypical autoinflammatory disease in patients could be modified by a synergistic effect with two other variants of autoinflammatory-associated genes.     

Replacement of owl monkey centromere satellite by a newly evolved variant was a recent and rapid process

Alpha satellite DNA is a major DNA component of primate centromeres. We previously reported that Azara's owl monkey has two types of alpha satellite DNA, OwlAlp1 and OwlAlp2. OwlAlp2 (344 bp) exhibits a sequence similarity throughout its entire length with alpha satellite DNA of closely related species. OwlAlp1 (185 bp) corresponds to the part of OwlAlp2. Based on the observation that the CENP-A protein binds to OwlAlp1, we proposed that OwlAlp1 is a relatively new repetitive DNA that replaced OwlAlp2 as the centromeric satellite DNA. However, a detailed picture of the evolutionary process of this centromere DNA replacement remains largely unknown. Here, we performed a phylogenetic analysis of OwlAlp1 and OwlAlp2 sequences, and also compared our results to alpha satellite DNA sequences of other primate species. We found that: (i) OwlAlp1 exhibits a higher similarity to OwlAlp2 than to alpha satellite DNA of other species, (ii) OwlAlp1 has a single origin, and (iii) sequence variation is lower in OwlAlp1 than in OwlAlp2. We conclude that OwlAlp1 underwent a recent and rapid expansion in the owl monkey lineage. This centromere DNA replacement could have been facilitated by the heterochromatin reorganization that is associated with the adaptation of owl monkeys to a nocturnal lifestyle.     

Clinical potential of hemodynamic ramp test by simultaneous echocardiography and right heart catheterization for aortic insufficiency in a patient with continuous-flow left ventricular assist device

Journal of Artificial Organs - Aortic insufficiency (AI) is an important adverse event in patients with continuous-flow (CF) left ventricular assist device (LVAD) support. AI is often progressive,...     

Lung miliary micro‐nodules in human T‐cell leukemia virus type I carriers

Human T‐cell leukemia virus type 1 (HTLV‐1) carriers are rarely subject to inflammatory disorders in multiple organs, other than the well‐known complication, adult T‐cell leukemia/lymphoma (ATLL). HTLV‐1 associated bronchiolo‐alveolar disorder (HABA) has been proposed as an immune mediated pulmonary reaction seen rarely in HTLV‐1 carriers. The reported clinico‐pathological patterns of HABA are diffuse panbronchiolitis (DPB) and lymphoid interstitial pneumonia (LIP). We here report three cases of HTLV‐1 carriers showing miliary micro‐nodules throughout both lungs. Microscopic examination in the video assisted thoracic surgery biopsies demonstrated that all cases had multiple discrete micro‐nodules which consisted of marked lymphoid infiltration, granulomas, eosinophils and a few foci of necrosis inside the granuloma. No findings indicating ATLL, other neoplastic conditions, infection or interstitial pneumonia, including DPB and LIP, were present following panels of special staining and immunohistochemical examinations. Two patients improved without treatment within one month, with no evidence of recurrence after 7 years. One patient showed slow deterioration of lung reticular shadows in spite of a low dose corticosteroid therapy (prednisolone 10 mg/day). We believe these cases may be a newly recognized variant of HABA.     

Numerical analysis of blood flow distribution in 4- and 3-branch vascular grafts

Trifurcated arch grafts (3-branch grafts) are now being used to repair the thoracic aorta in addition to conventional arch grafts (4-branch grafts). The anatomical shape of the 3-branch graft is different from the original vessel, so it is necessary for clinical application to evaluate blood flow distribution in the graft to assess whether there is adequate blood flow to the target organs. To achieve this, we developed a computational fluid dynamics (CFD) method to evaluate blood flow distribution in the grafts. Aortic blood flow was measured by phase-contrast magnetic resonance imaging (PC-MRI), and flow distribution into the branched vessels was obtained. The MRI image was used to create a patient-specific image model that represents the geometry of the aortic arch. The CFD analysis method was employed to determine a boundary condition of the blood flow analysis in the aorta using a patient-specific image model. We also created simplified models of 4-branch and 3-branch grafts and used our CFD analysis method to compare blood flow distribution among simplified models. It was found that blood flow distribution in the descending aorta was 71.3 % for the 4-branch graft and 67.7 % for the 3-branch graft, indicating that a sum of branching flow in the 3-branch graft was almost the same as the one in the 4-branch graft. Therefore, there is no major concern about implanting a new 3-branch graft. Our CFD analysis method may be applied to estimate blood flow distribution of a newly developed vascular graft prior to its clinical use and provide useful information for safe use of the graft.     

A new protocol for the preparation of superconducting KBi2

A superconducting KBi₂ sample was successfully prepared using a liquid ammonia (NH₃) technique. The temperature dependence of the magnetic susceptibility (M/H) showed a superconducting transition temperature (T_c) as high as 3.6 K. In addition, the shielding fraction at 2.0 K was evaluated to be 87%, i.e., a bulk superconductor was realized using the above method. The T_c value was the same as that reported for the KBi₂ sample prepared using a high-temperature annealing method. An X-ray diffraction pattern measured based on the synchrotron X-ray radiation was analyzed using the Rietveld method, with a lattice constant, a, of 9.5010(1) Å under the space group of Fd$\bar{3}$m (face-centered cubic, no. 227). The lattice constant and space group found for the KBi₂ sample using a liquid NH₃ technique were the same as those reported for KBi₂ through a high-temperature annealing method. Thus, the superconducting behavior and crystal structure of the KBi₂ sample obtained in this study are almost the same as those for the KBi₂ sample reported previously. Strictly speaking, the magnetic behavior of the superconductivity was different from that of a KBi₂ sample reported previously, i.e., the KBi₂ sample prepared using a liquid NH₃ technique was a type-II like superconductor, contrary to that prepared using a high-temperature annealing method, the reason for which is fully discussed. These results indicate that the liquid NH₃ technique is effective and simple for the preparation of a superconducting KBi₂. In addition, the topological nature of the superconductivity for KBi₂ was not confirmed.

A superconducting KBi₂ sample was successfully prepared using a liquid ammonia (NH₃) technique.