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A systematic comparison of mathematical models for inherent measurement of ciliary length: how a cell can measure length and volume.
Ludington, WB, Ishikawa, H, Serebrenik, YV, Ritter, A, Hernandez-Lopez, RA, Gunzenhauser, J, Kannegaard, E, Marshall, WF
Biophysical journal. 2015;(6):1361-1379
Abstract
Cells control organelle size with great precision and accuracy to maintain optimal physiology, but the mechanisms by which they do so are largely unknown. Cilia and flagella are simple organelles in which a single measurement, length, can represent size. Maintenance of flagellar length requires an active transport process known as intraflagellar transport, and previous measurements suggest that a length-dependent feedback regulates intraflagellar transport. But the question remains: how is a length-dependent signal produced to regulate intraflagellar transport appropriately? Several conceptual models have been suggested, but testing these models quantitatively requires that they be cast in mathematical form. Here, we derive a set of mathematical models that represent the main broad classes of hypothetical size-control mechanisms currently under consideration. We use these models to predict the relation between length and intraflagellar transport, and then compare the predicted relations for each model with experimental data. We find that three models-an initial bolus formation model, an ion current model, and a diffusion-based model-show particularly good agreement with available experimental data. The initial bolus and ion current models give mathematically equivalent predictions for length control, but fluorescence recovery after photobleaching experiments rule out the initial bolus model, suggesting that either the ion current model or a diffusion-based model is more likely correct. The general biophysical principles of the ion current and diffusion-based models presented here to measure cilia and flagellar length can be generalized to measure any membrane-bound organelle volume, such as the nucleus and endoplasmic reticulum.
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Analysis of masseter muscle oxygenation and mandibular movement during experimental gum chewing with different hardness.
Yoshida, T, Ishikawa, H, Yoshida, N, Hisanaga, Y
Acta odontologica Scandinavica. 2009;(2):113-21
Abstract
OBJECTIVE The purpose of this study was to analyze masseter muscle oxygenation changes and mandibular movements in the experimental chewing of gums with different hardness. MATERIAL AND METHODS Subjects for this experiment comprised 23 male volunteers with normal occlusion. Mean age (SD) was 28.3 (2.2) years. Three kinds of gum with mean fracture stresses of 3.52 x 10(4) N/m(2) (Gum 1), 5.35 x 10(4) N/m(2) (Gum 2), and 14.0 x 10(4) N/m(2) (Gum 3) were used. The subjects were instructed to chew gum for 80 s (100 strokes) on the voluntary chewing side at a pace of 1.25 strokes/s. Oxygen saturation in the masseter muscle and mandibular movement during gum chewing were recorded simultaneously using near-infrared spectroscopy tissue oximetry and mandibular kinesiography. RESULTS For Gum 1, no subjects showed any significant changes in oxygen saturation during gum chewing. For Gum 2, 10 subjects showed no significant changes, whereas the other 13 showed significant decreases in oxygen saturation. For Gum 3, significant decreases were seen in all subjects. Chewing motions were larger and velocity was higher in gum chewing with decreases in masseter muscle oxygen saturation compared to chewing showing no significant changes. CONCLUSIONS The results suggest that the harder texture of gum enlarges chewing motion and increases chewing velocity, with an increase in the contribution of anaerobic metabolism to energy yield in masseter muscle. Differences in the responses to gum hardness may indicate individual differences in muscle fatigue tendencies when chewing harder foods.
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Comparison between valsartan and valsartan plus cilnidipine in type II diabetics with normo- and microalbuminuria.
Katayama, K, Nomura, S, Ishikawa, H, Murata, T, Koyabu, S, Nakano, T
Kidney international. 2006;(1):151-6
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Abstract
Cilnidipine, an L-/N-type calcium channel blocker, dilates the efferent glomerular arterioles in an experimental model and shows a renoprotective effect, but its clinical benefits and safety have not yet been assessed in type II diabetics with albuminuria. The objective of this trial was to evaluate the effect of reducing albuminuria in type II diabetic patients with a combination therapy consisting of valsartan plus cilnidipine versus monotherapy with valsartan. An open-label, randomized controlled trial was conducted from April 2002 to October 2003 in 87 Japanese patients aged 31-90 years with type II diabetes showing albuminuria (urinary albumin/creatinine ratio: 10-300 mg/g). The patients were randomized to receive either valsartan (n=41) or valsartan plus cilnidipine (n=46) once daily for 1 year. The primary end point was the percent change in the albumin/creatinine ratio. The secondary end points were the progression/regression of albuminuria, blood pressure (BP), renal function, and safety. After 1 year, the albumin/creatinine ratio was found to have decreased more markedly in the valsartan plus cilnidipine group than in the valsartan group (reduction rate -44+/-11% (s.e.) versus -9+/-7% (s.e.); P=0.014 by analysis of covariance). Although a significant reduction was observed in the systolic and diastolic BP of both groups from baseline to 1 year (P<0.0001, respectively), there was no significant difference in the change in the BP between the two groups (systolic BP, P=0.066; diastolic BP, P=0.391). There were also no significant differences in the side effects between the two groups. Cilnidipine was thus found to show an additive effect with valsartan and thereby caused a reduction in albuminuria in type II diabetics.
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Aged garlic extract prevents a decline of NK cell number and activity in patients with advanced cancer.
Ishikawa, H, Saeki, T, Otani, T, Suzuki, T, Shimozuma, K, Nishino, H, Fukuda, S, Morimoto, K
The Journal of nutrition. 2006;(3 Suppl):816S-820S
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Abstract
Aged garlic extract (AGE) has manifold biological activities including immunomodulative and antioxidative effects. It is used as a major component of nonprescription tonics and cold-prevention medicines or dietary supplements. Advanced-cancer patients decline in immune functions and quality of life (QOL). The study's subjects were patients with inoperable colorectal, liver, or pancreatic cancer. In a randomized double-blind trial, AGE was administered to one group and a placebo was administered to another for 6 mo. The primary endpoint was a QOL questionnaire based on the Functional Assessment of Cancer Therapy (FACT). The subendpoints were changes in the natural-killer (NK) cell activity the salivary cortisol level from before and after administering AGE. Out of 55 patients invited to participate in the trial, 50 (91%) consented to enroll. They consisted of 42 patients with liver cancer (84%), 7 patients with pancreatic cancer (14%), and 1 patient with colon cancer (2%). Drug compliance was relatively good in both the AGE and placebo groups. Although no difference was observed in QOL, both the number of NK cells and the NK cell activity increased significantly in the AGE group. No adverse effect was observed in either group. The study showed that administering AGE to patients with advanced cancer of the digestive system improved NK cell activity, but caused no improvement in QOL.