The chimeric antibody chLpMab-7 targeting human podoplanin suppresses pulmonary metastasis via ADCC and CDC rather than via its neutralizing activity

Podoplanin (PDPN/Aggrus/T1α) binds to C-type lectin-like receptor-2 (CLEC-2) and induces platelet aggregation. PDPN is associated with malignant progression, tumor metastasis, and poor prognosis in several types of cancer. Although many anti-human PDPN (hPDPN) monoclonal antibodies (mAbs), such as D2-40 and NZ-1, have been established, these epitopes are limited to the platelet aggregation-stimulating (PLAG) domain (amino acids 29-54) of hPDPN. Recently, we developed a novel mouse anti-hPDPN mAb, LpMab-7, which is more sensitive than D2-40 and NZ-1, using the Cancer-specific mAb (CasMab) method. The epitope of LpMab-7 was shown to be entirely different from that of NZ-1, a neutralizing mAb against the PLAG domain according to an inhibition assay and lectin microarray analysis. In the present study, we produced a mouse-human chimeric anti-hPDPN mAb, chLpMab-7. ChLpMab-7 showed high antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). Furthermore, chLpMab-7 inhibited the growth of hPDPN-expressing tumors in vivo. Although chLpMab-7 recognizes a non-PLAG domain of hPDPN, it suppressed the hematogenous metastasis of hPDPN-expressing tumors. These results indicated that chLpMab-7 suppressed tumor development and hematogenous metastasis in a neutralization-independent manner. In conclusion, hPDPN shows promise as a target in the development of a novel antibody-based therapy

Effects of implementing rotational thromboelastometry in cardiac surgery: A retrospective cohort study

Since 2013, rotational thromboelastometry has been available in our hospital to assess coagulopathy. The aim of the study was to retrospectively evaluate the effect of thromboelastometry testing in cardiac surgery patients. Altogether 177 patients from 2012 and 177 patients from 2014 were included. In 2014, the thromboelastometry testing was performed on 56 patients. The mean blood drainage volume decreased and the number of patients receiving platelets decreased between 2012 and 2014. In addition, the use of fresh frozen plasma units decreased, and the use of prothrombin complex concentrate increased in 2014. When studied separately, the patients with a thromboelastometry testing received platelets, fresh frozen plasma, fibrinogen and prothrombin complex concentrate more often, but smaller amounts of red blood cells. In conclusion, after implementing the thromboelastometry testing to the practice, the blood products were given more cautiously overall. The use of thromboelastometry testing was associated with increased possibility to receive coagulation product transfusions. However, it appears that thromboelastometry testing was mostly used to assist in management of major bleeding.</p

Weight reduction by using a formula diet recovers menstruation in obese patients with an ovulatory disorder

Aim: To determine the effectiveness of a formula diet in weight reduction and the recovery of menstruation in obese patients with ovulatory disorders. Methods: After the enrollment of 39 obese women with ovulatory disorders, they replaced one or two of their three normal meals with a microdiet (MD) (240 kcal/meal) for 24 weeks. Physical, endocrinological, and biochemical tests were conducted before and at 12 and 24 weeks of the study. Of the 39 women enrolled, 26 were not taking clomiphene. They were divided into three groups according to their body weight outcomes and then analyzed for menstruation recovery. Results: A weight reduction of ≥5% was observed in 31 (81.5%) of the 39 women. There were significant decreases in the body weight and Body Mass Index during the study. Menstruation returned in 18 (69%) of the 26 patients without clomiphene treatment, with the recovery being significantly more prevalent in the groups (totally 81.0%) that exhibited a 5%‐10% weight reduction and ≥10% weight reduction, compared to the group with a <5% weight reduction. Conclusion: The use of a formula diet effectively reduced the patients’ body weight and led to the recovery of menstruation in these obese patients with ovulatory disorders

Open-label clinical trial of bezafibrate treatment in patients with fatty acid oxidation disorders in Japan

IntroductionFatty acid oxidation disorders (FAODs) are rare diseases caused by defects in mitochondrial fatty acid oxidation (FAO) enzymes. While the efficacy of bezafibrate, a peroxisome proliferator-activated receptor agonist, on the in vitro FAO capacity has been reported, the in vivo efficacy remains controversial. Therefore, we conducted a clinical trial of bezafibrate in Japanese patients with FAODs.Materials and methodsThis trial was an open-label, non-randomized, and multicenter study of bezafibrate treatment in 6 patients with very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency and 2 patients with carnitine palmitoyltransferase-II (CPT-2) deficiency (median age, 8.2 years; ranging from 5.8 to 26.4 years). Bezafibrate was administered for 6 months following a 6-month observation period. The primary endpoint was the frequency of myopathic attacks, and the secondary endpoints were serum acylcarnitines (ACs, C14:1 or C16 + C18:1), creatine kinase (CK) levels, degree of muscle pain (VAS; visual analog scale) during myopathic attacks, and quality of life (QOL; evaluated using validated questionnaires).ResultsThe frequency of myopathic attacks after bezafibrate administration decreased in 3 patients, increased in 3, and did not change in 2. The CK, AC, and VAS values during attacks could be estimated in only three or four patients, but a half of the patients did not experience attacks before or after treatment. Changes in CK, AC, and VAS values varied across individuals. In contrast, three components of QOL, namely, physical functioning, role limitation due to physical problems (role physical), and social functioning, were significantly elevated. No adverse drug reactions were observed.ConclusionIn this study, the frequency of myopathic attacks and CK, AC, and VAS values during the attacks could not be evaluated due to several limitations, such as a small trial population. Our findings indicate that bezafibrate improves the QOL of patients with FAODs, but its efficacy must be examined in future investigations

Optimal Timing of Insecticide Fogging to Minimize Dengue Cases: Modeling Dengue Transmission among Various Seasonalities and Transmission Intensities

Dengue virus infection is a serious infectious disease transmitted by Aedes mosquitoes in the tropics and sub-tropics. Disease control often involves the use of insecticide fogging against mosquito vectors. However, the effectiveness of this method for reducing dengue cases, in addition to appropriate application procedures, is still debated. The previous mathematical simulation study reported that insecticide fogging reduces dengue cases most effectively when applied soon after the epidemic peak; however, the model did not take into account seasonality and population immunity, which strongly affect the epidemic pattern of dengue infection. Considering these important factors, we used a mathematical simulation model to explore the most effective time for insecticide fogging and to evaluate its impact on reducing dengue cases. Simulations were conducted with various lengths of the wet season and population immunity levels. We found that insecticide fogging substantially reduces dengue cases if conducted at an appropriate time. In contrast to the previously suggested application time during the peak of disease prevalence, the optimal timing is relatively early: between the beginning of the dengue season and the prevalence peak

Change in monthly mean temperatures in Singapore.

<p>Change in monthly mean temperatures in Singapore.</p

Change in the threshold mosquito density.

<p>The effect of a 5% change in each parameter after univariate sensitivity analysis.</p

Threshold mosquito density at various population immunity levels and numbers of serotypes.

<p>Simulations were conducted at a constant temperature of 25°C. Threshold MPP is the number of female mosquitoes per person that causes an epidemic (10% increase of seroprevalence). A lower threshold MPP indicates a higher probability of epidemics.</p

Comparison of the threshold mosquito density resulting in R₀ = 1.

<p>Dark green bars represent <i>m</i> calculated by <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0048258#pone.0048258.e002" target="_blank">equation 2 </a><a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0048258#pone.0048258-Yang1" target="_blank">[16]</a> and light green bars represent our result (MPP_R0 = 1).</p