Effect of anticomplement agent K-76 COOH in hamster-to-rat and guinea pig- to-rat xenotransplantation

In normal rats, the xenobiotic K76 inhibited the C5 and probably the C2 and C3 steps of complement and effectively depressed classical complement pathway activity, alternative complement pathway activity, and the C3 complement component during and well beyond the drug's 3-hr half-life. It was tested alone and with intramuscular tacrolimus (TAC) and/or intragastric cyclophosphamide (CP) in rat recipients of heterotopic hearts from guinea pig (discordant) and hamster (concordant) donors. Single prevascularization doses of 100 and 200 mg/kg increased the median survival time of guinea pig hearts from 0.17 hr in untreated controls to 1.7 hr and 10.2 hr, respectively; with repeated injections of the 200-mg dose every 9-12 hr, graft survival time was increased to 18.1 hr. Pretreatment of guinea pig heart recipients for 10 days with TAC and CP, with or without perioperative splenectomy or infusion of donor bone marrow, further increased median graft survival time to 24 hr. Among the guinea pig recipients, the majority of treated animals died with a beating heart from respiratory failure that was ascribed to anaphylatoxins. Hamster heart survival also was increased with monotherapy using 200 mg/kg b.i.d.i.v. K76 (limited by protocol to 6 days), but only from 3 to 4 days. Survival was prolonged to 7 days with the addition to K76 of intragastric CP at 5 mg/kg per day begun 1 day before operation (to a limit of 9 days); it was prolonged to 4.5 days with the addition of intramuscular TAC at 2 mg/kg per day beginning on the day of transplantation and continued indefinitely. In contrast to the limited efficacy of the single drugs, or any two drugs in combination, the three drugs together (K76, CP, and TAC) in the same dose schedules increased median graft survival time to 61 days. Antihamster antibodies rapidly increased during the first 5 days after transplantation, and plateaued at an abnormal level in animals with long graft survival times without immediate humoral rejection. However, rejection could not be reliably prevented, and was present even in most of the xenografts recovered from most of the animals dying (usually from infection) with a beating heart. Thus, although effective complement inhibition with K76 was achieved in both guinea pig- and hamster-to-rat heart transplant models, the results suggest that effective interruption of the complement cascade will have a limited role, if any, in the induction of xenograft acceptance

Fabrication of a 64-Pixel TES Microcalorimeter Array with Iron Absorbers Uniquely Designed for 14.4-keV Solar Axion Search

If a hypothetical elementary particle called an axion exists, to solve the strong CP problem, a 57Fe nucleus in the solar core could emit a 14.4-keV monochromatic axion through the M1 transition. If such axions are once more transformed into photons by a 57Fe absorber, a transition edge sensor (TES) X-ray microcalorimeter should be able to detect them efficiently. We have designed and fabricated a dedicated 64-pixel TES array with iron absorbers for the solar axion search. In order to decrease the effect of iron magnetization on spectroscopic performance, the iron absorber is placed next to the TES while maintaining a certain distance. A gold thermal transfer strap connects them. We have accomplished the electroplating of gold straps with high thermal conductivity. The residual resistivity ratio (RRR) was over 23, more than eight times higher than a previous evaporated strap. In addition, we successfully electroplated pure-iron films of more than a few micrometers in thickness for absorbers and a fabricated 64-pixel TES calorimeter structure.Comment: 5 pages, 5 figures, published in IEEE Transactions on Applied Superconductivity on 8 March 202

Burn-associated delayed dilated cardiomyopathy evaluated by cardiac PET and SPECT: Report of a case

AbstractDilated cardiomyopathy is a delayed-onset and rarely reported cardiac complication of burn injury although the mechanism remains unclear. We thus report a case of dilated cardiomyopathy following severe burn injury, in which technetium 99m sestamibi single-photon emission computed tomography (SPECT), iodine-123 beta-methyl-iodophenylpentadecanoic acid SPECT and 18F-fluorodeoxyglucose positron emission tomography (PET) were performed to evaluate the pathophysiologic condition in combination with cardiac catheterization and myocardial biopsy. The cardiac PET and SPECT images showed reduced myocardial blood flow, decreased fatty acid metabolism, and increased glucose utilization in the left ventricular lateral wall in spite of normal coronary angiography, no significant cardiac fibrosis, and inflammatory cell infiltration, which suggests that myocardial ischemia due to microcirculatory disturbance in hypermetabolic state associated with burn injury might be a causative mechanism of dilated cardiomyopathy in this case. A beta blocker, bisoprolol, was successfully introduced in this patient in combination with oral inotropic agents, pimobendan and digitalis after the prolonged use of intravenous dobutamine infusion, which might have been beneficial for this patient with burn-associated dilated cardiomyopathy not only to reduce regional myocardial ischemia but also to attenuate hypermetabolic state after severe burn injury.<Learning objective: Dilated cardiomyopathy complicated with burn injury has been reported to cause a sudden attack of dyspnea and death. This case report suggests that burn-associated dilated cardiomyopathy may be caused by relative myocardial ischemia due to microvascular disturbance in hypermetabolic state associated with burn injuries and can be treated effectively with beta blockers with or without oral inotropic agents.

Reproducibility and validity of food group intake in a short food frequency questionnaire for the middle-aged Japanese population

Purpose: The purpose of this study was to evaluate the reproducibility and validity of a short food frequency questionnaire (FFQ) for food group intake in Japan, the reproducibility and partial validity of which were previously confirmed for nutrients. Methods: A total of 288 middle-aged healthy volunteers from 11 different areas of Japan provided nonconsecutive 3-day weighed dietary records (DRs) at 3-month intervals over four seasons. We evaluated reproducibility based on the first (FFQ1) and second (FFQ2) questionnaires and their validity against the DRs by comparing the intake of 20 food groups. Spearman’s rank correlation coefficients (SRs) were calculated between energy-adjusted intake from the FFQs and that from the DRs. Results: The intake of 20 food groups estimated from the two FFQs was mostly equivalent. The median energy-adjusted SRs between the FFQ1 and FFQ2 were 0.61 (range 0.38–0.86) for men and 0.66 (0.45–0.84) for women. For validity, the median de-attenuated SRs between DRs and the FFQ1 were 0.51 (0.17–0.76) for men and 0.47 (0.23–0.77) for women. Compared with the DRs, the proportion of cross-classification into exact plus adjacent quintiles with the FFQ1 ranged from 58 to 86% in men and from 57 to 86% in women. According to the robust Z scores and the Bland–Altman plot graphs, the underestimation errors in the FFQ1 tended to be greater in individuals with high mean levels of consumption for meat for men and for other vegetables for both men and women. Conclusion: The FFQ demonstrated high reproducibility and reasonable validity for food group intake. This questionnaire is short and remains appropriate for identifying associations between diet and health/disease among adults in Japan

Comparison of weighed food record procedures for the reference methods in two validation studies of food frequency questionnaires

Background: Although open-ended dietary assessment methods, such as weighed food records (WFRs), are generally considered to be comparable, differences between procedures may influence outcome when WFRs are conducted independently. In this paper, we assess the procedures of WFRs in two studies to describe their dietary assessment procedures and compare the subsequent outcomes. Methods: WFRs of 12 days (3 days for four seasons) were conducted as reference methods for intake data, in accordance with the study protocol, among a subsample of participants of two large cohort studies. We compared the WFR procedures descriptively. We also compared some dietary intake variables, such as the frequency of foods and dishes and contributing foods, to determine whether there were differences in the portion size distribution and intra- and inter-individual variation in nutrient intakes caused by the difference in procedures. Results: General procedures of the dietary records were conducted in accordance with the National Health and Nutrition Survey and were the same for both studies. Differences were seen in 1) selection of multiple days (non-consecutive days versus consecutive days); and 2) survey sheet recording method (individual versus family participation). However, the foods contributing to intake of energy and selected nutrients, the portion size distribution, and intra- and inter-individual variation in nutrient intakes were similar between the two studies. Conclusion: Our comparison of WFR procedures in two independent studies revealed several differences. Notwithstanding these procedural differences, however, the subsequent outcomes were similar

Safety confirmation of induced pluripotent stem cell-derived cardiomyocyte patch transplantation for ischemic cardiomyopathy: first three case reports

IntroductionWith the expected increase in patients with heart failure and ischemic 15 cardiomyopathy, the development of myocardial regenerative medicine using cell transplantation as a novel treatment method is progressing. This first-in-human clinical trial aimed to confirm the safety of cardiomyocyte patch transplantation derived from allogeneic induced pluripotent stem (iPS) cells based on the results of several preclinical studies.Study designThe inclusion criteria were left ventricular ejection fraction of 35% or less; heart failure symptoms of New York Heart Association class III or higher despite existing therapies such as revascularization; and a 1-year observation period that included a 3-month immunosuppressive drug administration period after transplantation of iPS cell-derived cardiomyocyte patches to evaluate adverse events, cardiac function, myocardial blood flow, heart failure symptoms, and immune response.ResultsIn the first three cases of this trial, no transplanted cell-related adverse events were observed during the 1-year observation period, and improvement in heart failure symptoms was observed. In addition, improvements in left ventricular contractility and myocardial blood flow were observed in two of the three patients. Regarding immune response, an increase in transplant cell-specific antibody titer was observed in all three patients after immunosuppressive drug administration. In one patient with poor improvement in cardiac function and myocardial blood flow, an increase in antibody titer against HLA-DQ was observed even before cell transplantation.ConclusionsOur case findings demonstrate that the transplantation of iPS cell-derived cardiomyocyte patches for ischemic cardiomyopathy can be safely performed; however, further investigation of the therapeutic effect and its relationship with an immune response is needed by accumulating the number of patients through continued clinical trials

The DNA damage responses: important determinants of the biological responses to radiation

The actions and biological effects of radiation are diverse and complex, starting from the early stages when radiation energy is deposited into the biological systems and DNA damage is induced, and continuing into the late stages when the actual health effects appear. To understand these processes comprehensively, knowledge from a broad range of fields will be needed, including physics, chemistry, biology and medicine. Ultimate biological consequences of radiation exposure depend not only on the doses, dose rates, fractionation, source and quality of radiation, but also on other factors, such as age, lifestyles, environments, tissue oxygen concentration, and genetic backgrounds that determine the repair capacity for DNA damages in each individual. Responses to the DNA damages are activated upon induction of any type of the DNA damages by radiological and non-radiological causes, and play a critical role in preventing clinically detectable adverse effects due to the DNA damages. Hereditary defects in the DNA damage responses lead to high-risk groups for radiation-induced diseases, including cancer, and in such "radiosensitive" populations, even low-dose radiation exposure can cause severe health effects. Further genetic and molecular biological approaches are needed to identify all the high-risk groups for radiation-induced diseases and to develop effective therapies for these conditions based on the radiosensitivity of each individual