Engagement of gaze in capturing targets for future sequential manual actions

We investigated the role of saccadic gaze fixations in encoding target locations for planning a future manual task consisting of a sequence of discrete target-oriented actions. We hypothesized that fixations of the individual targets are necessary for accurate encoding of target locations and that there is a transfer of sequence information from visual encoding to manual recall. Subjects viewed four targets presented at random positions on a screen. After various delays following target extinction, the subjects marked the remembered target locations on the screen with the tip of a hand-held stick. When the targets were presented simultaneously among distracting elements, the overall accuracy of marking increased with presentation time and total number of targets fixated because the subjects had to serially fixate the individual targets to locate them. Without distractors, the marking accuracy was similarly high regardless of duration of target presentation (0.25-8 s) and number of targets fixated; it was comparable to that with distractors when all four targets had been fixated. This indicates parallel encoding of target locations largely based on peripheral vision. Location memory was stable in these tasks over the delay periods investigated (0.5-8 s). With parallel encoding there was a "shrinkage" in the visuomotor transformation, i.e., the distances between the markings were systematically smaller than the corresponding inter-target distances. When the targets were presented sequentially without distractors, marking accuracy improved with the total number of targets fixated and shrinkage in the visuomotor transformation occurred only with parallel encoding, i.e., when subjects did not fixate the targets. In all experimental conditions for trials in which targets were fixated during encoding, there was little correspondence between the marking sequence and the sequence in which the targets were fixated. We conclude that subjects benefit from fixating targets for subsequent target-oriented manual actions when the targets are presented among distractors and when presented sequentially; when distinct targets are presented simultaneously against a blank background, they are efficiently encoded in parallel largely by peripheral vision.     

Intestinal microflora and aging: Age-related change of lipid metabolism in germ-free and conventional rats

The influence of intestinal microflora and aging on the lipid metabolism in germfree (GF) and conventional (CV) rats, 8 and 40 weeks old, was investigated. Serum cholesterol at the age of 8 and 40 weeks and serum triglyceride (TG) at the age of 40 weeks was higher in GF than in CV rats. Serum cholesterol decreased and serum TG and corticosterone tended to increase in both GF and CV rats with aging. In the rats 40 weeks of age, lipase activity of the pancreas and the duodenal, jejunal, and colorectal contents in GF rats increased, but that of the ileal and cecal contents in GF and CV rats decreased. Intestinal microflora tended to depress the age-related increase of serum TG and lipase activity of the pancreas and the duodenal and jejunal contents Lipoprotein lipase (LPL) and hormone-sensitive lipase (HSL) activities of the epididymal adipose tissue were higher in CV than in GF rats at both 8 and 40 weeks of age. The LPL activity increased and the HSL activity decreased in both GF and CV rats with aging. The concentration of cholesterol increased and that of bile acids decreased in the cecal contents of 40-week-old GF rats.     

Allelic homogeneity due to a founder mutation in Japanese patients with lattice corneal dystrophy type IIIA

Lattice corneal dystrophies (LCDs) are caused by mutations of the transforming growth factor beta-induced gene (TGFBI, formerly betaig-h3). LCD type IIIA (LCDIIIA) has been reported mostly from Japan. In this study, we demonstrate allelic homogeneity for Japanese patients with LCDIIIA, using intragenic polymorphic markers. When exon 11 of TGFBI was analyzed, all 18 patients examined were found to be heterozygous for both a P501T mutation and an IVS10-3C --> T variation. On the other hand, none of 54 normal Japanese control subjects had the P501T, and 5 of the controls were heterozygous for IVS10-3C --> T. Haplotype analysis of the patients revealed that both P501T and IVS10-3C --> T were located on the same chromosome, and a significant linkage disequilibrium (P < 0.001, Fisher's exact probability test) was observed between LCDIIIA (P501T) and IVS10-3C --> T. When exon 8 of the gene was analyzed, all these patients possessed the "G allele" of a 1028G/A polymorphism. A significant linkage disequilibrium (P < 0.003; chi-square test) was also observed between P501T and the G allele in the patients. These results suggest that allelic homogeneity seen in Japanese patients with LCDIIIA may result from a single founder mutation.     

Photodegradation behavior of some vinyl ketone copolymers

Photodegradation behavior for copolymers of styrene (St), α-methyl styrene (α-MSt) and methyl methacrylate (MMA) with methyl vinyl ketone (MVK) and phenyl vinyl ketone (PVK) in the presence of air was investigated in the solid state and in solution. Photolysis of St/MVK and St/PVK copolymers proceeded smoothly and an increase of the ketone in the copolymer resulted in an increase of the rate of degradation. Generally, the rate of degradation is faster in St/PVK copolymers than in St/MVK copolymers. It is likely that the degradation of the copolymers takes place mainly through NORRISH type II reaction. It was found that the photolysis of α-MSt/PVK copolymers was retarded considerably as compared with St/PVK copolymers. An unexpected behavior was observed in the case of MMA/MVK or MMA/PVK copolymers. These copolymers were expected to degrade with slow rates; they degraded, however, rapidly. Some experiments were done to explain this phenomenon.     

Inhibitory effects of procaine on the contractile responses of the guinea-pig Taenia caecum to acetylcholine,substance P and potassium chloride

Summary The effect of procaine on the contractile responses to acetylcholine, substance P and KCl was investigated using the isolated guinea-pig taenia caecum. In normal Tyrode solution (37°C), procaine (10–100 mol/l) caused a parallel shift to the right of only the dose-response curve of acetylcholine (pA₂ value, 5.11). The pA₂ value of procaine against acetylcholine was not significantly affected by increasing the Ca concentration in the bathing solution from 0.9 to 7.2 mmol/l. On the other hand, a high concentration of procaine (10 mmol/l) caused a transient contraction of the taenia caecum, but completely suppressed contractions to all concentrations of the agonists. In K-depolarized preparations, procaine (1–10 mmol/l) shifted the dose-response curve for the CaCl₂-induced contraction to the right. Substance P (3 mol/l)-induced contraction of the taenia caecum incubated with Ca-free EGTA (0.1 mmol/l) solution (20°C) was markedly reduced by procaine (10 mmol/l). Using the single sucrose-gap technique, it was found that procaine (10 mmol/l) produced a membrane depolarization and increases in both amplitude and frequency of spontaneous spike discharge. These potential changes were still observed even after the procaine-induced contraction had disappeared. The spike discharges and contraction caused by procaine were abolished in the presence of a Ca-entry blocker, verapamil (10 mol/l). From these observations, it is concluded that at low concentrations procaine acts as a competitive antagonist of muscarinic receptors in the guinea-pig taenia caecum while high concentrations of procaine may depress the contractile responses to acetylcholine, substance P and KCl by inhibiting the Ca-induced Ca release from the intracellular store site or by reducing the transmembrane Ca influx during depolarization.     

Nitrogen-containing bisphosphonates and lipopolysaccharide mutually augment inflammation via adenosine triphosphate (ATP)-mediated and interleukin 1β (IL-1β)-mediated production of neutrophil extracellular traps (NETs)

Among the bisphosphonates (BPs), nitrogen-containing BPs (N-BPs) have much stronger anti–bone-resorptive actions than non-N–BPs. However, N-BPs have various side effects such as acute influenza-like reactions after their initial administration and osteonecrosis of the jawbones after repeated administration. The mechanisms underlying such effects remain unclear. To overcome these problems, it is important to profile the inflammatory nature of N-BPs. Here, we analyzed the inflammatory reactions induced in mouse ear pinnae by the N-BPs alendronate (Ale) and zoledronate (Zol). We found the following: (i) Ale and Zol each induced two phases of inflammation (early weak and late strong ear swelling); (ii) both phases were augmented by lipopolysaccharides (LPSs; cell-surface constituent of gram-negative bacteria, including oral bacteria), but prevented by inhibitors of the phosphate transporters of solute carrier 20/34 (SLC20/SLC34); (iii) macrophages and neutrophils were involved in both phases of Ale+LPS–induced ear-swelling; (iv) Ale increased or tended to increase various cytokines, and LPS augmented these effects, especially that on interleukin 1β (IL-1β); (v) adenosine triphosphate (ATP) was involved in both phases, and Ale alone or Ale+LPS increased ATP in ear pinnae; (vi) the augmented late-phase swelling induced by Ale+LPS depended on both IL-1 and neutrophil extracellular traps (NETs; neutrophil-derived net-like complexes); (vii) neutrophils, together with macrophages and dendritic cells, also functioned as IL-1β–producing cells, and upon stimulation with IL-1β, neutrophils produced NETs; (viii) stimulation of the purinergic 2X7 (P2X7) receptors by ATP induced IL-1β in ear pinnae; (ix) NET formation by Ale+LPS was confirmed in gingiva, too. These results suggest that (i) N-BPs induce both early-phase and late-phase inflammation via ATP-production and P2X7 receptor stimulation; (ii) N-BPs and LPS induce mutually augmenting responses both early and late phases via ATP-mediated IL-1β production by neutrophils, macrophages, and/or dendritic cells; and (iii) NET production by IL-1β–stimulated neutrophils may mediate the late phase, leading to prolonged inflammation. These results are discussed in relation to the side effects seen in patients treated with N-BPs. © 2021 American Society for Bone and Mineral Research (ASBMR).     

Treatment results of radiotherapy to both the prostate and metastatic sites in patients with bone metastatic prostate cancer

Although systemic therapy is the standard treatment for metastatic prostate cancer, a randomized controlled trial showed radiotherapy to the prostate improved overall survival of metastatic prostate cancer patients with the low metastatic burden. Additionally, a randomized phase II trial showed that metastasis-directed therapy for oligo-recurrent prostate cancer improved androgen-deprivation therapy (ADT)-free survival. Therefore, administering radiotherapy to both prostate and metastatic regions might result in better outcomes. Thus, we report the treatment results of radiotherapy to both prostate and metastatic regions. Our institutional database was searched for patients who received radiotherapy to the prostate and metastatic regions. We summarized patient characteristics and treatment efficacy and performed statistical analysis to find possible prognostic factors. A total of 35 patients were included in this study. The median age was 66 years, and the median initial prostate-specific antigen (PSA) level was 32 ng/ml. The Gleason score was 7 in 10 patients, 8 in 13 patients, and 9 in 12 patients. The median radiotherapy dose was 72 Gy to the prostate and 50 Gy to the metastatic bone region. The 8-year overall survival, cause-specific survival, progression-free survival, and freedom from biochemical failure rate were 81, 85, 53, and 57%. Among the 35 patients, 12 were disease-free even after ADT was discontinued. In selected patients with metastatic prostate cancer, ADT and radiotherapy to the prostate and metastatic sites were effective. Patients with good response to ADT may benefit from radiotherapy to both prostate and metastatic regions.     

Tumor Necrosis Factor Gene Polymorphism in Chronic Sinusitis

Objectives It is likely that genetic factors play a role in the etiology of chronic sinusitis, and airway inflammation is an important pathological feature in chronic sinusitis. We hypothesized that individuals with greater inflammatory responses may be more likely to acquire the disease. Polymorphisms of the tumor necrosis factor (TNF) genes have been described, and certain inflammatory diseases are reportedly associated with certain alleles of TNF genes. The purpose of this study is to examine whether there is an association between some alleles of TNF genes and chronic sinusitis. Study Design Thirty‐eight Japanese patients with intractable chronic sinusitis were selected on the basis of the following criteria: 1) persistent mucous or mucopurulent nasal discharge and/or postnasal dripping for longer than 3 years and 2) opacification in bilateral maxillary sinuses and ethmoid cells on plain radiographic films. Methods Both tumor necrosis factor‐α (TNF‐α) and tumor necrosis factor‐β (TNF‐β) gene polymorphisms were analyzed by polymerase chain reaction (PCR) with restriction fragment length polymorphisms in these patients and 35 healthy control subjects. Results A significantly higher frequency (P < .05) of TNFB*2 allele of TNF‐β gene polymorphism was observed in patients with chronic sinusitis (74%) compared with control subjects (56%). There was no association between alleles of TNF‐α and chronic sinusitis. Conclusion We concluded that TNF‐β gene polymorphism may form a component of the genetic predisposition to chronic sinusitis in Japanese patients.     

Relationship between self-rating and polygraphic sleep parameters — analysis of compiled data from 12 young Japanese adults —

An examination of the relationship of the self-rating sleep score to polygraphic sleep parameters was conducted. The self-rating sleep questionnaire, OSA, includes five sleep quality factors: sleepiness (Fl), sleep maintenance without interruption (F2), worry about daily life or poor emotional condition (F3), integrated or perceived sleep feeling (F4) and sleep initiation or induction (F5). Polygraphic sleep parameters including each sleep stage in minutes were used. If intercorrelation coefficients exceeded 0.8, only one of the related parameters was selected for multivariate analysis. Twelve male students slept a total of 88 nights, among which the first night was not included, in an experimental room. When absolute values of Spearman’s rank correlation coefficient of not less than 0.4 were tentatively selected, the following pairs were extracted: F2 score and S1 (-0.423) or S3+S4 (0.409), F5 score and sleep latency (-0.439). Deeper sleep was closely associated with sleep maintenance without interruption. Agreement between self-rating and a polygraphic sleep parameter was recognized between the F5 score and sleep latency. Each OSA factor score was predicted by other polygraphic sleep parameters using multiple regression analysis. MT significantly contributed to the Fl, F3 and F4 scores. The number of stage shifts per night significantly contributed to the Fl and F3 scores, and the number of sleep spindles significantly contributed to the F5 score. Though prediction of sleep quality by polygraphic sleep parameters is limited, the association between concrete subjective and objective sleep parameters was clarified as mentioned above, and their practical meaning was partially elucidated.     

Suppression of neointimal thickening by a newly developed HMG-CoA reductase inhibitor,BAYw6228, and its inhibitory effect on vascular smooth muscle cell growth

1. The aim of this study was to determine whether BAYw6228 (BAYw), a newly developed 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase inhibitor, could suppress an atherogenic process such as intimal thickening by a mechanism other than lowering the level of serum cholesterol.
2. First, we evaluated the in vitro effect of BAYw on the proliferation of vascular smooth muscle cells (SMC) from various species: Sprague-Dawley (SD) rats, New Zealand (NZ) white rabbits, intimal cells from Watanabe hereditary hyperlipidemic (WHHL) rabbit and SMC from the new-born human aorta. The increasing rate of total protein content of these cells was inhibited by the addition of BAYw in a dose-dependent fashion. In the presence of 2% foetal calf serum (FCS), the value of IC₅₀ was 1.0 μM in SD rats. 2.1 μM in NZ white rabbits, and 0.3 μM in WHHL rabbits. With human SMC, the value was 0.02 μM in the presence of 10% FCS and 0.2 μM with a mixture of growth factors.
3. Based on these above in vitro findings, we next examined the in vivo effect of the agent to determine whether it could suppress rabbit intimal thickening induced by balloon catheterization. A balloon catheter was inserted from a peripheral branch of the left external carotid artery to the aorta to denude the endothelium of the left common carotid artery in Japanese white rabbits. After 12 days they were divided into control and BAYw groups. The former were subcutaneously injected with saline and the latter with BAYw 1 mg kg⁻¹ day⁻¹. Two days after the beginning of treatment, a second balloon injury was performed to the previously injured left common carotid artery in both groups. After another two weeks, the left common carotid artery was removed and variously stained. Although the total serum cholesterol in the BAYw group was significantly lower than in the control (P<0.05), the difference was not enough to affect intimal thickening. In addition, the BAYw group had a smaller intima/media ratio than the control group, decreasing to 45% of control (P<0.05). By anti-α smooth muscle actin antibody staining, these intimal thickening areas were entirely occupied by SMCs, and their amount was attenuated by BAYw. By anti-rabbit macrophage antibody (RAM 11) staining, the number of positive cells in the intimal thickening was markedly decreased in the BAYw group compared to control (P<0.01).
4. These results indicate that BAYw has an inhibitory effect on intimal thickening by attenuating intimal SMC proliferation and infiltration of macrophages, suggesting that BAYw could be effective in the prevention of the progression of atherosclerotic plaque-like restenosis after angioplasty.