Advances and Challenges of Antibody Therapeutics for Severe Bronchial Asthma

Asthma is a disease that consists of three main components: airway inflammation, airway hyperresponsiveness, and airway remodeling. Persistent airway inflammation leads to the destruction and degeneration of normal airway tissues, resulting in thickening of the airway wall, decreased reversibility, and increased airway hyperresponsiveness. The progression of irreversible airway narrowing and the associated increase in airway hyperresponsiveness are major factors in severe asthma. This has led to the identification of effective pharmacological targets and the recognition of several biomarkers that enable a more personalized approach to asthma. However, the efficacies of current antibody therapeutics and biomarkers are still unsatisfactory in clinical practice. The establishment of an ideal phenotype classification that will predict the response of antibody treatment is urgently needed. Here, we review recent advancements in antibody therapeutics and novel findings related to the disease process for severe asthma.     

7Li 2D CSI of human brain on a clinical scanner

Lithium salts have been widely used in the treatment of mood disorders, but the mechanism of action is still not clear. In this work, a methodology for two-dimensional Lithium-7 imaging on clinical systems is presented. The data were acquired using a phosphorus volume head coil that was re-tuned for the Lithium-7 frequency. A spectroscopic sequence was used to acquire the free induction decay (FID) after volume excitation using a hard pulse. The results obtained on the head of patients undergoing lithium treatment (n = 7, 0.6 mEq/1 average serum level) demonstrate that images of adequate signal to noise ratio (100:1) can be obtained in acceptable imaging times (55 min) using the proposed methodology. The distribution of ’’Li appears uniform in the brains of the patients studied.     

On the so-called “semi-ionic” C–F bond character in fluorine–GIC

The short-range structures of fluorine–graphite intercalation compounds with stage-1 structures, C_xF (x = 2.47, 2.84, 3.61), were analyzed by means of neutron diffraction. It has been shown that the so-called “semi-ionic” C–F bond character in C_xF is essentially covalent with the bond length of 0.140 nm, and the original planar graphene sheets are buckled at the sp³-hybridized carbon atoms bound to fluorine atoms. Conjugated C–C double bonds with the bond length of 0.142 nm are preserved between the carbon atoms unbound to fluorine atoms in C_xF, while other C–C bonds are single bonds with the bond lengths of 0.153 nm. The C–F bond order in C_xF is slightly lower than those in poly(carbon monofluoride) ((CF)_n) and poly(dicarbon monofluoride) ((C₂F)_n), which is explained by the hyperconjugation involving the C–C bonds on the carbon sheets and C–F bond.     

Thermal molecular motion at surface of atactic polypropylene films

Surface molecular motion in atactic polypropylene (aPP) films was studied by scanning force microscopy. Glass transition temperature at the surface, T_g^s, was determined to be 251±1 K on the basis of temperature dependence of lateral force, whereas its bulk glass transition temperature, T_g^b, by dynamic viscoelastic and differential scanning calorimetric measurements was 262 K. In general, polyolefin is easily oxidized, and thus, many kinds of additives are mixed in it for practical use. Hence, effects of oxidation and additives on surface properties of the aPP surface were examined as well. To achieve oxidation, the aPP films were annealed at 428 K for 100 min under the ambient atmosphere. After this treatment, T_g^s decreased by approximately 15 K in comparison with the intact film due to degradation of surface chains. On the contrary, in the case of the aPP containing 10 wt% antioxidant, T_g^s was almost the same as that of the intact film before and even after the oxidation treatment.     

Fabrication of tin-filled carbon nanofibres by microwave plasma vapour deposition and their in situ heating observation by environmental transmission electron microscopy

Sn-filled carbon nanofibres (CNFs) are fabricated by microwave plasma chemical deposition. Scanning electron microscopy observations revealed the existence of a Sn island under the CNFs. The structure of the CNFs is investigated, and the behaviour of Sn in the internal space of CNFs is revealed by performing in situ heating observations by environmental transmission electron microscopy (ETEM). ETEM observations reveal that they have low-crystallized carbon wall and Sn occupies not only the CNF’s internal space but also its carbon wall. The Sn inside the CNF is completely covered by the carbon wall. Further, the in situ heating observations reveal that Sn within the internal space and the carbon wall of the CNFs diffused to the outside during heating. Moreover, it is found that higher membered carbon rings and defects in the graphite layer act as diffusion routes between disordered carbon layers.     

Preparation and characteristics of dextran-methyl methacrylate graft copolymer

A graft polymer of dextran-methyl methacrylate (MMA) has been prepared using ceric nitrate. The solubility, infra-red absorption spectrum and thermal behaviour of the graft copolymer together with those of dextran and PMMA have been studied. It was found that a hot-pressed film of the copolymer not only shows better water wettability and water absorbing power than PMMA but also thrombo-resistance, and can be shaped into a transparent contact lens having an affinity for tears and blood. High resolution electron scanning microscopy shows that the surface of the contact lens has a micro-heterogeneous structure, consisting of phase separated grains of about 0.2 μm in size which are distributed uniformly.     

Cancer-associated retinopathy syndrome: a case of small cell lung cancer expressing recoverin immunoreactivity

Cancer-associated retinopathy (CAR) syndrome is a rare paraneoplastic neuropathy syndrome often found in patients with small cell lung cancer (SCLC). Serological studies have indicated that the process could include autoimmune reactions directing retinal antigens. Recently, the CAR antigen was identified as a photoreceptor protein, recoverin, by screening retinal proteins using the CAR patient's serum. The present case of SCLC showed rapidly deteriorated bilateral visual acuity lacking the inflammatory findings at the retina which were compatible with CAR. The immunohistochemical study revealed that the cancer cells expressed recoverin or recoverin-like immunoreactivity. This is the first observation in CAR syndrome. The presence of recoverin or recoverin-like immunoreactivity in SCLC with CAR syndrome supports the hypothesis that the cancer-retina immunologic cross-reaction contributes to visual loss in this syndrome.     

Identification of five novel germline mutations of the MEN1 gene in Japanese multiple endocrine neoplasia type 1 (MEN1) families

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder characterised by tumours of the parathyroid glands, the anterior pituitary, and endocrine pancreas. The MEN1 gene has recently been cloned and germline mutations have been identified in MEN1 patients in the United States, Canada, and Europe. We examined MEN1 gene mutations in MEN1 and MEN1 related cases in eight unrelated Japanese families. These families include five familial MEN1 (FMEN1), two sporadic MEN1 (SMEN1), and one familial hyperparathyroidism (FHP). Direct sequence analysis of the protein coding regions was carried out in all the probands. We identified six different heterozygous mutations in the coding region, of which five were novel, including one missense mutation (E45G) in both FMEN1 and SMEN1, three deletions (569del, 711del, and 1350del3) in FMEN1 and FHP, and two nonsense mutations (R29X and Y312X) in FMEN1 and SMEN1. Only one of these mutations (Y312X) has previously been reported. One proband with FMEN1 had no mutation in the entire exon sequence including the 5' and 3' untranslated regions. A restriction digestion analysis of 19 relatives from the five families showed a close correlation between the existence of the MEN1 gene mutation and disease onset. Four different polymorphisms, including two novel ones, were identified. These findings imply that a diversity of MEN1 gene mutations exists in Japanese MEN1 and MEN1 related disease, suggesting that analysis of the entire coding region of the MEN1 gene is required for genetic counselling in Japan.