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Biomedical subjects

Yoshio Nakamura

Publications and source records attributed to Yoshio Nakamura.

At least 19 recordsLinked to original sources

Cerebral cortical dysfunction in patients with temporomandibular disorders in association with jaw movement observation.

Temporomandibular disorders (TMD) represent a group of chronic painful conditions in the masticatory musculature and temporomandibular joint. To examine possible changes in cortical machinery in TMD patients, we compared neuromagnetic signals evoked by cortical neurons between healthy subjects and TMD patients while they were carefully observing the video frames of jaw-opening movements performed by another person. During the movement observation task in the healthy subjects, we found cortical activation in the following sequence with left hemisphere dominance: (1) the occipitotemporal region near the inferior temporal sulcus (human homologue of MT/V5 in monkeys), (2) the inferior parietal cortex (IPC), and (3) the anterior part of the inferior-lateral precentral gyrus (PrCG). In the TMD patients, however, we found deficit or marked attenuation of the neuromagnetic responses in the PrCG and IPC, while the activity of the MT/V5 showed no differences from that in the healthy subjects. In addition, we could not find any differences in cortical magnetic responses between healthy subjects and TMD patients when they were observing palm-opening movements, indicating that cortical dysfunction associated with jaw-movement observation is specific phenomena in the patients of TMD. Thus the present study provides new neuropathological evidence that TMD patients exhibit dysfunction of recognition mechanisms in cerebral cortex during motor observation, and suggests that disturbance of cortical functions regulating visuomotor integration would play a crucial role in development as well as aggravation of TMD.

Adult↗

Steroid pulse therapy impaired endothelial function while increasing plasma high molecule adiponectin concentration in patients with IgA nephropathy.

BACKGROUND: Decreased plasma adiponectin is associated with impaired endothelial function and, thereby, increased risk for cardiovascular events. Glucocorticoid (GC) affects vascular endothelial cells either favourably or harmfully depending upon the dosages and duration. We examined the effect of GC pulse therapy on vascular endothelial function. METHODS: Fourteen young patients with IgA nephropathy were evaluated for flow-mediated vasodilation (FMD), plasma levels of adiponectin both in high molecular weight (HMW adiponectin) form and in single molecular form (total adiponectin), hepatocyte growth factor (HGF), asymmetric dimethylarginine (ADMA), and high-sensitive C-reactive protein, before and after a course of GC pulse therapy. RESULTS: GC pulse therapy significantly decreased FMD (from 7.2 +/- 2.6 to 5.7 +/- 2.5%, P < 0.01). Meanwhile, plasma adiponectin levels were significantly augmented (total adiponectin: from 10.2 +/- 4.0 to 12.1 +/- 6.3 microg/ml, P < 0.05; HMW: from 6.5 +/- 3.2 to 7.7 +/- 3.3 microg/ml, P < 0.05). In parallel, elevated concentrations of serum HGF (from 0.28 +/- 0.12 to 0.63 +/- 0.38 ng/ml, P < 0.01) and plasma ADMA (from 0.45 +/- 0.07 to 0.53 +/- 0.04 nmol/ml, P < 0.05) were observed. CONCLUSIONS: GC pulse therapy impaired endothelial function while increasing plasma adiponectin levels, which may in turn restore the endothelial function in patients with IgA nephropathy.

Adiponectin↗

Significant and prolonged antisense effect of a multifunctional envelope-type nano device encapsulating antisense oligodeoxynucleotide.

A multifunctional envelope-type nano device (MEND) was developed for use as an efficient non-viral system for the delivery of plasmid DNA (pDNA) using octaarginine (R8) as an internalizing ligand. Three types of R8-MENDs were prepared, co-encapsulating luciferase-encoding pDNA and anti-luciferase oligodeoxynucleotide (ODN) condensed by three polycations, stearyl octaarginine (STRR8), poly-L-lysine (PLL) and protamine, and the antisense effects of the ODN-encapsulated R8-MENDs (ODN-MEND) were analysed in-vitro. The ODN-MEND packaged using protamine as a condenser showed a 90% antisense effect 16 h after the transfection, and a persistent antisense effect of over 75% for up to 48 h, which was much more effective than that of LipofectAmine2000. On the other hand, the ODN-MENDs prepared using PLL and STR-R8 as condensers did not show any significant inhibition of luciferase activity. Although there was no specific relation between the physicochemical characteristics of the ODN-MENDs and their antisense effect, the pattern of the antisense effect among the ODN-MENDs was similar to that of the silencing effect of R8-MEND encapsulating plasmid DNA encoding siRNA. These results suggest that R8-MENDs are able to deliver encapsulated DNA to the cytosol as well as to the nucleus, and that protamine can also function as an efficient decondenser, not only in the nucleus but also in the cytosol. In conclusion, we successfully developed an ODN-MEND with a high antisense effect using protamine as a DNA condensing as well as a decondensing agent.

Amino Acid Sequence↗

Back pain claim rates in Japan and the United States: framing the puzzle.

STUDY DESIGN: This is a cross-national comparison of workers' compensation claims for back pain in Japan and the United States (US). OBJECTIVES: The main objective is to juxtapose rates of back pain claims in Japan and Washington state. Because the Washington state rate closely matches rates for other US states as well as the rate for the US as a whole, it is used to represent the US rate. A puzzle is to be framed: Why are back pain claim rates in Japan and the United States so disparate? SUMMARY OF BACKGROUND DATA: Occupational back pain is common among workers in both Japan and the United States. Wage compensation for time off work is also substantial in both countries and potentially induces time off work at least as much in Japan as in the United States. Accordingly, back pain claim rates in Japan seemingly would be on the same order of magnitude as rates in the United States. METHODS: Washington state rates are based on data from its state fund. Both Japan and Washington state rates are composed of the number of workers eligible to file worker compensation claims in a given year (denominator) and the number of back pain claims accepted during that year (numerator). Because rates may fluctuate from year-to-year, 5 years of data on rates are presented, 1995-1999. Central to the comparison are Japanese and Washington state rates of workers' compensation claims for back pain with more than 3 days compensated time loss from work. RESULTS: The back pain claim rate in 1999 was 60 times higher in Washington state than in Japan. The disparity in rates for the other years in the study (1995-1998) was similar. CONCLUSION: Back pain is common among workers both in Japan and the United States, but there is no simple or necessary relationship between that symptom and how it manifests itself in one country or another. Rather, the symptom is protean in its social manifestations. As for what shapes those manifestations-or, more specifically, what causes the startling disparity in back pain claim rates between Japan and the United States-that is a puzzle. Various solutions to the puzzle are discussed, but it remains essentially unsolved.

Back Pain↗

National Institutes of Health grant awards for pain, nausea, and dyspnea research: an assessment of funding patterns in 2003.

UNLABELLED: We introduce an interactive database that permits description and exploration of National Institutes of Health (NIH) funding patterns for research on pain, nausea, and dyspnea. The database encompasses both basic science and clinical research. This article describes how we created the database, including the procedures we developed for reviewing and classifying research grants. In addition, it reports NIH grants and funding activity for the year 2003, with a breakdown of funding activity by Institute and funding comparisons across Institutes. It also describes a first attempt to identify clinically significant but underfunded research domains. In 2003, the NIH funded 1148 grants having relevance to the domain of pain, representing 2.5% of the total NIH research budget. Of those, 581 grants, or about 1% of the NIH budget, had a primary focus on pain. Of the diseases and conditions addressed by the current implementation, musculoskeletal conditions were the best represented with 105 grants, whereas cardiac conditions had the fewest number of grants with 7. The NIH funded 43 grants for dyspnea research and a scant 29 grants for nausea studies. We discuss the current limitations of the database and our plans for further development. PERSPECTIVE: The interactive database and classification system for pain, nausea, and dyspnea research funded by the NIH reported on in this article represents an objective and verifiable resource for health policy makers and others interested in NIH funding decisions. The high inter-rater reliability achieved attests to the objectivity of the classification method. Initial analyses demonstrate that these data can usefully track funding patterns by NIH institutes and reveal underfunded areas of research.

Budgets↗

Greater adenosine A(2A) receptor densities in cardiac and skeletal muscle in endurance-trained men: a [11C]TMSX PET study.

We examined the densities of adenosine A(2A) receptors in cardiac and skeletal muscles between untrained and endurance-trained subjects using positron emission tomography (PET) and [7-methyl-11C]-(E)-8-(3,4,5-trimethoxystyryl)-1,3,7-trimethylxanthine ([11C]TMSX), a newly developed radioligand for mapping adenosine A(2A) receptors. Five untrained and five endurance-trained subjects participated in this study. The density of adenosine A(2A) receptors was evaluated as the distribution volume of [11C]TMSX in cardiac and triceps brachii muscles in the resting state using PET. The distribution volume of [11C]TMSX in the myocardium was significantly greater than in the triceps brachii muscle in both groups. Further, distribution volumes [11C]TMSX in the trained subjects were significantly grater than those in untrained subjects (myocardium, 3.6+/-0.3 vs. 3.1+/-0.4 ml g(-1); triceps brachii muscle, 1.7+/-0.3 vs. 1.2+/-0.2 ml g(-1), respectively). These results indicate that the densities of adenosine A(2A) receptors in the cardiac and skeletal muscles are greater in the endurance-trained men than in the untrained men.

Adult↗

Development of efficient packaging method of oligodeoxynucleotides by a condensed nano particle in lipid envelope structure.

An efficient delivery system is required if antisense oligodeoxynucleotides (ODN) are to be utilized for gene therapy. We report herein on the development of a novel ODN delivery system, ODN-encapsulated nano particles (ODN-ENP) using an efficient and simple packaging method. The ODN-ENP consists of a condensed ODN particle and a lipid envelope, which can be equipped with various functional devices for the efficient delivery of ODN with a small diameter (150 nm). The encapsulation efficiency and ODN recovery of ODN-ENP were significantly higher than those of other packaging methods, such as a stabilized antisense-lipid particles method or a freeze-thaw method. Furthermore, the time required for the preparation of the ODN-ENP was shorter than the other methods. The method developed in this study is a simple and efficient packaging method for ODN with a condensed nano particle in lipid-envelope structure.

Base Sequence↗

Passive triceps surae stretch inhibits vasoconstriction in the nonexercised limb during posthandgrip muscle ischemia.

We investigated whether selective muscle mechanoreceptor activation in the lower limb opposes arm muscle metaboreceptor activation-mediated limb vasoconstriction. Seven subjects completed two trials: one control trial and one stretch trial. Both trials included 2 min of handgrip and 2 min of posthandgrip exercise muscle ischemia (PEMI). In the stretch trial, a 2-min sustained triceps surae stretch, by brief passive dorsiflexion of the right foot, was performed simultaneously during PEMI. Mean arterial pressure, heart rate, and forearm blood flow (FBF) in the nonexercised arm and forearm vascular conductance (FVC) in the nonexercised arm were measured. During PEMI in the control trial, mean arterial pressure was significantly greater and FBF and FVC were significantly lower than baseline values (P < 0.05 for each). In contrast, FBF and FVC during PEMI in the stretch trial exhibited different responses than in the control trial. FBF and FVC were significantly greater in the stretch trial than in the control trial (FBF, 5.5 +/- 0.4 vs. 3.8 +/- 0.4 ml x 100 ml(-1) x min(-1); FVC, 0.048 +/- 0.004 vs. 0.033 +/- 0.003 unit, respectively; P < 0.05). These results indicate that passive triceps surae stretch can inhibit vasoconstriction in the nonexercised forearm mediated via muscle metaboreceptor activation in the exercised arm.

Adult↗

Potential of [11C]TMSX for the evaluation of adenosine A2A receptors in the skeletal muscle by positron emission tomography.

We examined the potential of [7-methyl-11C]-(E)-8-(3,4,5-trimethoxystyryl)-1,3,7-trimethylxanthine ([11C]TMSX) for the assessment of adenosine A2A receptors in muscle. In rodents, specific binding of [11C]TMSX was observed in muscle and heart by blockade with A2A-selective CSC and non-selective theophylline, but not with A1-selective DPCPX. Swimming exercise fluctuated radioligand-receptor binding in these tissues. In a PET study of two subjects, theophylline-infusion slightly deceased the distribution volume of [11C]TMSX in the heart (20% reduction) and muscle (10% reduction), which suggested the specific binding.

Adult↗

Rhythm generation for food-ingestive movements.

In vitro block preparations of the central nervous system (CNS) are particularly valuable for study of central neuronal mechanisms controlling the respiratory and locomotor rhythms. No comparable in vitro preparation has been described previously, however, for analysis of analogous feeding rhythms. In this chapter, we present such a model. It is comprised of an in vitro brainstem-spinal cord preparation isolated from the newborn rat and mouse. Bath application to this preparation of N-methyl-D-aspartate (NMDA) induces rhythmical burst activity in the V, VII and XII nerves, which, collectively, is indicative of feeding behavior. Selected transections of the brainstem reveal that the central sucking rhythm generators for such V, VII and XII activity are separate from one another, and located segmentally in the brainstem at the level of their respective motor nuclei. We believe that use of this in vitro preparation will advance understanding of the central neuronal mechanisms controlling sucking and mastication, and the developmental transition from sucking to mastication.

Animals↗

Pancreatic endocrine tumor in Japan.

Japanese clinicians and scientists have contributed significantly to reporting, investigating, and managing patients with pancreatic endocrine tumors and other multiple endocrine neoplasias for the past several decades. This article summarizes the latest progress in this field in Japan. Particularly, our contribution to the development of diagnostic and localization methods is reviewed. Further, the present use of somatostatin receptor scintigraphy and the application of the laparoscopic surgery for pancreatic endocrine tumor in Japan are discussed.

Calcium↗

The role of adrenomedullin and receptors in glomerular hyperfiltration in streptozotocin-induced diabetic rats.

BACKGROUND: Since adrenomedullin (AM) elicits vasodilatation by binding to specific AM receptors consisted of calcitonin-receptor-like receptor (CRLR)/receptor-activity-modifying protein 2 (RAMP2) or CRLR/receptor-activity-modifying protein 3 (RAMP3) on endothelial cells and stimulating nitric oxide production, AM possibly involves in glomerular capillary dilatation in early phase of diabetic nephropathy. METHODS: Streptozotocin (STZ)-induced diabetic Sprague-Dawley rats at 4 weeks after the injection were employed for expression studies of AM, RAPM2, and RAMP3. The measurement of AM peptide levels in kidney tissue, plasma, and urine was performed. Human aortic endothelial cells (HAEC) were used to investigate functional link between glucose-induced AM production and nitric oxide release. RESULTS: STZ rats showed glomerular hypertrophy and increased urinary NO2- and NO3- excretion. By Northern blot analyses, AM and RAPM2 mRNAs significantly increased in the kidneys of STZ rats, while RAMP3 mRNA was not altered. In STZ rats, AM peptide was actively secreted into urine (1280 +/- 360 fmol/day vs. control 110 +/- 36 fmol/day). AM peptide was mainly detected on cortical and medullary collecting duct cells in control rat kidneys and AM peptide and mRNA were up-regulated on afferent arterioles and glomeruli of STZ rats. RAMP2 expression was detected on afferent arterioles and not in glomeruli in control rats and it was up-regulated on glomerular endothelial cells in STZ rats. In HAEC culture, d-glucose stimulated AM and nitric oxide production and they were suppressed by addition of AM antisense oligodeoxynucleotides. CONCLUSION: Up-regulated expression of AM and RAMP2 in afferent arterioles and glomeruli may be related to selective dilatation of glomerular capillary in acute phase of type 1 diabetes.

Adrenomedullin↗

Practical efficacy of telmisartan for decreasing morning home blood pressure and pulse wave velocity in patients with mild-to-moderate hypertension.

The current guideline-recommended blood pressure values are difficult to maintain in general practice, partly due to the lack of ideal anti-hypertensive agents. Since morning hypertension has a high correlation with cardiovascular events, expectations that telmisartan, a long-acting angiotensin-II type-1 receptor blocker (ARB), can improve cardiovascular mortality are high. In this study, the efficiency of telmisartan in reducing morning hypertension and pulse wave velocity (PWV) as a practical surrogate endpoint was investigated. Seventeen unsupervised and 7 untreated hypertensive patients were prescribed telmisartan 40 mg/day for 3 months. Medication already prescribed upon enrollment in this study was continued, with the exception of ARBs (all of which turned out to be losartan 50 mg/day), which were discontinued and replaced with telmisartan. Morning home blood pressure (MHBP), office blood pressure (OBP), and brachial-ankle PWV (baPWV) were investigated in a prospective fashion. A stratified analysis was performed regarding previous use (group L) or non-use (group N) of losartan. Over a 3-month period, telmisartan was found to significantly reduce both OBP (from 153+/-13/85+/-9 to 141+/-17/80+/-7 mmHg (p <0.01)) and MHBP (from 153+/-23/93+/-11 to 137+/-22/82+/-10 mmHg (p <0.001)). Surprisingly, 7 patients (70%) from group L achieved an OBP of less than 140/90 mmHg by simply changing their medication to telmisartan. Furthermore, baPWV fell significantly from 1,892+/-334 cm/s to 1,672+/-324 cm/s (p <0.01), which was greater than the change in baPWV estimated by OBP reduction. Here it must be mentioned that there were no significant differences between group L and group N in the courses of blood pressures and baPWV. In conclusion, telmisartan 40 mg/day was found to be effective for reducing MHBP and arterial wall stiffness in patients with mild-to-moderate hypertension, and thus may also be effective for improving cerebrocardiovascular mortality.

Aged↗

Regional differences in blood flow and oxygen consumption in resting muscle and their relationship during recovery from exhaustive exercise.

This investigation evaluated regional differences in blood flow and oxygen consumption and their relationship in exercised muscle during recovery from exhaustive exercise. Five healthy men performed exhaustive one-legged cycling exercise. Positron emission tomography was used to measure blood flow, oxygen uptake, and oxygen extraction in the quadriceps femoris muscle before and after exercise. Regions of interest included five areas of the muscle (two proximal, one central, and two distal), which were evenly spaced across the muscle. Before exercise, blood flow and oxygen consumption decreased significantly (P < 0.05) in the direction from the proximal to the distal portions; blood flow declined from 2.0 +/- 0.5 to 1.4 +/- 0.3 ml x 100 g-1 x min-1, and oxygen consumption decreased from 0.21 +/- 0.04 to 0.17 +/- 0.02 ml.100 g-1x min-1. In contrast, these gradients in blood flow and oxygen consumption diminished during recovery after exercise. Consequently, there was a positive relationship between changes in blood flow and oxygen consumption in an exercised muscle during recovery after exercise (r = 0.963, P < 0.01). These changes became larger in the direction from proximal to distal portions: blood flow increased from 2.9 +/- 0.7 to 3.9 +/- 0.8 and oxygen consumption from 1.4 +/- 0.1 to 1.8 +/- 0.4 times resting values. These results suggest that hemodynamic variables are heterogeneous within a muscle both at rest and during recovery from exercise and that there is a systematic difference in these variables in the direction from proximal to distal regions within the quadriceps femoris muscle.

Adult↗