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Biomedical subjects

Makoto Wada

Publications and source records attributed to Makoto Wada.

18 recordsLinked to original sources
PubMed2006

SKL-2841, a dual antagonist of MCP-1 and MIP-1 beta, prevents bleomycin-induced skin sclerosis in mice.

Systemic sclerosis (SSc) is a connective tissue disease characterized by fibrosis and excessive collagen deposition in the skin and various internal organs. In early stages of SSc, the dermis reveals infiltration of inflammatory cells associated with increased collagen synthesis. SKL-2841 was initially synthesized as a novel small molecule antagonist of MCP-1. In this study, we indicated that SKL-2841 also exerts anti-chemotactic activity for MIP-1 beta in mouse spleen cells. In the early stages of bleomycin-induced skin lesions, immunohistochemical analysis showed the expression of both MCP-1 and MIP-1 beta in dermal inflammatory cells. Moreover, intraperitoneal administration of SKL-2841 suppressed the infiltration of inflammatory mononuclear cells and polymorphonuclear cells in the acute phase and also significantly suppressed fibrillization in the chronic phase in bleomycin-induced scleroderma, compared with PBS treatment. These findings suggest that SKL-2841 has potential as a compound for the treatment of conditions associated with skin fibrosis such as SSc.

Animals↗
PubMed2006

Statistical parametric mapping of immunopositive cell density.

We developed a new method for comparing immunopositive cell densities across groups of animals and creating statistical parametric maps on standardized sections. As an example, we compared Iba-1 (microglial marker) positive cell densities in rats with (n=6) and without (n=6) unilateral injection of 1-methyl-4-phenylpyridinium salt (MPP+). Immunopositive cells were automatically counted in each animal over a coronal section in the midbrain (bregma -5.9 mm) and a positive cell density map was created for each animal. After the positive cell density map was normalized to a template section from an atlas, positive cell densities of the two groups were compared in each pixel over the section and a statistical parameter (p-value from t-test) was mapped on each pixel. We were able to detect significant increases of microglias in the side of MPP+ injection not only in the substantia nigra pars compacta but also in adjacent white matter. We also applied the same analysis to tyrosine hydroxylase stained sections and detected significant decreases of dopamine neurons in the side of MPP+ injection. The new method was proven to be useful for detecting significant changes of cell densities over the entire area of immunostained sections.

1-Methyl-4-phenylpyridinium↗
PubMed2006

Combination therapy of prednisolone and mizoribine improves cryoglobulinemic vasculitis with purpura and skin ulcers.

Conventional treatment is not standardized for hepatitis C virus-negative cryoglobulinemia, but corticosteroids, immunosuppressive agents, and plasma exchange typically improved the symptoms. Mizoribine is an immunosuppressive agent that was developed in Japan and has been found to inhibit the proliferation of lymphocytes, especially B cells. We have encountered an elder patient who had hepatitis C virus-negative, type II cryoglobulinemic vasculitis with leg purpura and skin ulcers. Her symptoms improved and cryoglobulin disappeared by the combination therapy of prednisolone and mizoribine. We speculate the action mechanism of this therapy is due to immunosuppressive effects including up-regulation of the efficacy of prednisolone by mizoribine.

Aged↗
PubMed2006

Nonenzymatic ligation of short-chained 2'-5'- or 3'-5'-linked oligoribonucleotides on 2'-5'- or 3'-5'-linked complementary templates.

5'-pACUG tetraribonucleotides containing 2'-5' or 3'-5' linkages self-condensed on 2'-5'- or 3'-5'-linked complementary decaribonucleotide (5'-CAGUCAGUCA) templates. CD and UV melting studies showed that helix formation took place in all four possible combinations of linkage isomers of the substrate tetramer and the template decamer under the ligation conditions. The hybridization ability followed the order: [3'-5' tetramer with 3'-5' decamer] > [2'-5' tetramer with 3'-5' decamer] > [2'-5' tetramer with 2'-5' decamer] > or = [3'-5' tetramer with 2'-5' decamer]. Each tetramer condensed on the complementary decaribonucletide template to form the corresponding octamer, but the ligation efficiency varied considerably, depending on the types of linkage in the tetramer substrate and the template decamer. The yields of the octamers obtained by the template-directed ligation followed the order: [2'-5' substrate: 2'-5' template] > [3'-5':3'-5'] > [2'-5':3'-5'] > [3'-5':2'-5']. The results demonstrate that a homo-linkage system is preferable for the template-directed synthesis of RNA. The resulting linkage of the octamer formed from the 2'-5'-linked substrate and the 2'-5'-linked template is mainly 2'-5'.

Nucleic Acid Conformation↗
PubMed2006

Effects of disease severity on response to lateral wedged shoe insole for medial compartment knee osteoarthritis.

OBJECTIVE: To determine the effects of lateral wedged insoles on knee kinetics and kinematics during walking, according to radiographic severity of medial compartment knee osteoarthritis (OA). DESIGN: A prospective case control study of patients with medial compartment OA of the knee. SETTING: Gait analysis laboratory in a university hospital. PARTICIPANTS: Forty-six medial compartment knees with OA of 23 patients with bilateral disease and 38 knees of 19 age-matched healthy subjects as controls. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: We measured the peak external adduction moment at the knee during the stance phase of gait and the first acceleration peak after heel strike at the lateral side of the femoral condyles. Kellgren and Lawrence grading system was used for radiographic assessment of OA severity. RESULTS: The mean value of peak external adduction moment of the knee was higher in OA knees than the control. Application of lateral wedged insoles significantly reduced the peak external adduction moment in Kellgren-Lawrence grades I and II knee OA patients. The first acceleration peak value after heel strike in these patients was relatively high compared with the control. Application of lateral wedged insoles significantly reduced the first acceleration peak in Kellgren-Lawrence grades I and II knee OA patients. CONCLUSIONS: The kinetic and kinematic effects of wearing of lateral wedged insoles were significant in Kellgren-Lawrence grades I and II knee OA. The results support the recommendation of use of lateral wedged insoles for patients with early and mild knee OA.

Aged↗
PubMed2006

Effect of compensation procedures for velocity on repeatability and variability of gait parameters in normal subjects.

UNLABELLED: OBJECTIVE To evaluate the effects of a mathematical procedure that adjusts for gait velocity on the variability seen in gait analysis. DESIGN: Evaluation before and after compensation. SETTING: Gait laboratory, Fukui University Hospital, Japan. SUBJECTS: Fourteen normal volunteers. OUTCOME MEASURES: A computerized gait analysis system with two forceplates and a light source spot measuring device was used. Gait measurement in each subject was performed on three different days. RESULTS: The gait parameters measured on three different days were significantly different, particularly step length, stride length, velocity, the components of floor-reaction forces and hip motion. In these parameters, intraclass correlation coefficient, ICC (1,1) was not high (range 0.05-0.71). However, there was a high correlation between these parameters and velocity and high repeatability was obtained following compensation for velocity (ICC (1,1), range 0.73-0.97). In contrast, compensation of parameters whose measurement was not significantly different before compensation did not improve ICC (1,1). Variability of all parameters was acceptable, however CV (an index of variability) improved significantly after compensation compared with that before compensation in six of 15 parameters. CONCLUSIONS: Our findings suggest that low repeatability in gait parameters should be considered even when the gait of normal subjects is measured on different days. A high repeatability and more acceptable variability were obtained when the data were compensated for velocity.

Analysis of Variance↗
PubMed2006

[A case of Henoch-Schönlein purpura with relapse of ileitis and duodenitis for a short period].

A 60-year old man admitted our hospital due to abdominal pain, melena and arthralgia. There was purpura on his legs. On admission, the abdominal CT showed segmental mural thickening of terminal ileum and ascites. On the 4th hospital day, the abdominal CT showed severe mural thickening of the third portion of duodenum. On the 8th hospital day, the abdominal CT showed severe mural thickening of terminal ileum. We reported a rare case of Henoch-Schönlein purpura with relapse of ileitis and duodenitis for a short period which could be examined on the abdominal CT.

Duodenitis↗
PubMed2005

Copper chelation with tetrathiomolybdate suppresses adjuvant-induced arthritis and inflammation-associated cachexia in rats.

Tetrathiomolybdate (TM), a drug developed for Wilson's disease, produces an anti-angiogenic and anti-inflammatory effect by reducing systemic copper levels. TM therapy has proved effective in inhibiting the growth of tumors in animal tumor models and in cancer patients. We have hypothesized that TM may be used for the therapy of rheumatoid arthritis and have examined the efficacy of TM on adjuvant-induced arthritis in the rat, which is a model of acute inflammatory arthritis and inflammatory cachexia. TM delayed the onset of and suppressed the severity of clinical arthritis on both paw volume and the arthritis score. Histological examination demonstrated that TM significantly reduces the synovial hyperplasia and inflammatory cell invasion in joint tissues. Interestingly, TM can inhibit the expression of vascular endothelial growth factor in serum synovial tissues, especially in endothelial cells and macrophages. Moreover, the extent of pannus formation, which leads to bone destruction, is correlated with the content of vascular endothelial growth factor in the serum. There was no mortality in TM-treated rat abnormalities. TM also suppressed inflammatory cachexia. We suggest that copper deficiency induced by TM is a potent approach both to inhibit the progression of rheumatoid arthritis with minimal adverse effects and to improve the well-being of rheumatoid arthritis patients.

Administration, Oral↗
PubMed2005

Temporal order judgment in mice.

A temporal order judgment task was developed for mice. After training male mice (C57BL6NCrj, n=15) to poke their noses into a hole, two stimuli (brief puffs of air) were delivered to the whiskers with a fixed interval of 750 ms in one of four orders: right (R)-left (L), L-R, L-L, and R-R. The mice were rewarded when they oriented their heads toward the first (n=5) or second (n=10) stimulus after a visual go signal. The mice were trained for up to 50 days. All mice met the criterion for task achievement (daily correct response rate >70% on 3 consecutive days) in response to unilateral stimuli (L-L and R-R), and 9 of the 15 mice met the criterion for task achievement in response to bilateral stimuli (L-R and R-L). The median periods for task achievement were 15 and 34 days for unilateral and bilateral stimuli, respectively. The correct response rate dropped to approximately the chance level after all whiskers had been removed. The nine successful mice were trained further and tested with smaller interstimulus intervals. The probability of right-first judgment plotted against the stimulation interval was fitted with a sigmoid function (r2=0.92) with asymptotes of 0.29 and 0.73 and a temporal resolution of 160 ms. The sigmoid curve was biased horizontally by 133 ms, reflecting the fact that stimuli delivered simultaneously were judged as left-first rather than right-first. The results show that mice can be trained to judge the temporal order of tactile stimuli delivered to whiskers and that such judgment might be lateralized to the right hemisphere.

Animals↗
PubMed2005

Effects of beta-thujaplicin on anti-Malassezia pachydermatis remedy for canine otitis externa.

The antifungal activity of beta-thujaplicin was evaluated against 51 Malassezia pachydermatis strains isolated from canine ear canals with or without otitis externa. For comparison, sensitivity tests were performed on M. pachydermatis isolates for nystatin, ketoconazole, and terbinafine HCl, all clinically available antifungal agents. The minimal inhibition concentrations over 50% of the tested isolates (MIC50) were 3.13 microg/ml for beta-thujaplicin and nystatin, 0.016 microg/ml for ketoconazole, and 1.56 microg/ml for terbinafine HCl. The antifungal effect for M. pachydermatis of beta-thujaplicin compared favorably with commercial antifungal agents. None of the 51 M. pachydermatis isolates showed resistance against any of the tested antibiotics investigated in this study. Ten representative isolates of M. pachydermatis were subcultured for 30 generations at concentrations close to the MIC levels of beta-thujaplicin, nystatin, ketoconazole, and terbinafine HCl, and examined to determine whether they had acquired resistance to each drug. As a result, M. pachydermatis was found to achieve resistance more easily for ketoconazole and terbinafine HCl than for beta-thujaplicin or nystatin. The MIC50 of beta-thujaplicin did not change during the course of subculture, and it is thought that the potential development of a resistant strain is low, even with continuous infusion for otitis externa therapy. beta-Thujaplicin is an inexpensive and safe treatment with anti-inflammatory and deodorant effects that can be recommended as an effective remedy for canine otitis externa.

Animals↗
PubMed2004

Cytometric analysis of adverse action of diphenyl ditelluride on rat thymocytes: cell shrinkage as a cytotoxic parameter.

Despite the growing use of organotellurium compounds in the chemical and biomedical fields, there has been no great concern about their toxicity until now. To test the possibility that diphenyl ditelluride (DPDT) and tellurium chloride (TeCl2), organic and inorganic tellurium compounds, may exert adverse action on mammals, their effects on rat thymocytes were examined under in vitro conditions using a flow cytometer with fluorescent probes. Incubation of thymocytes with DPDT at 300 nM or more for 24 h significantly increased the populations of shrunken cells and of cells with hypodiploidal DNA. Z-VAD-FMK, a paninhibitor of caspases, greatly suppressed the DPDT-induced increase in the hypodiploidal cell population, suggesting the involvement of caspase activation in DPDT toxicity. Hence, it is possible that DPDT would increase the population of thymocytes undergoing apoptosis if the blood concentration in mammals reached at least 300 nM or more. TeCl2 was much less potent than DPDT in increasing the population of hypodiploidal cells.

Animals↗
PubMed2004

Effects of handedness on tactile temporal order judgment.

We examined effects of handedness on the judgment of temporal order of successive taps delivered to both hands. When the subjects' arms were uncrossed, the temporal resolution (84% correct responses) of right-handed subjects (52 +/- 4 ms, n = 16) was significantly better than that of left-handed subjects (83 +/- 9 ms, n = 16). When their arms were crossed, both groups tended to invert their judgment to a similar extent at intervals as long as 200-300 ms. In the arms crossed condition, right handed subjects inverted their judgment more often in response to left-hand-first stimuli than to right-hand-first stimuli, whereas left-handed subjects did not show the same asymmetry. We infer that hemispheric lateralization, which is generally stronger in right- than in left-handed subjects, contributes to the relatively better temporal resolution of right-handed subjects in the uncrossed condition, as well as to the asymmetric effect of stimulation order in the crossed condition.

Adolescent↗
PubMed2003

Re-examination of the value of localising aura sensations and lateralising interictal epileptiform discharges in view of structural lesions demonstrated by MRI.

We examined the relationship between MRI lesions and electro-clinical findings with special attention to the localising value of aura sensations and the sides of interictal epileptiform discharges in 327 patients with symptomatic localisation-related epilepsy. As a result, while autonomic as well as psychic auras were correlated with temporal lesions, simple motor seizures were associated with extra-temporal ones. Within the group of patients with temporal lobe epilepsy, autonomic but not psychic auras concurred significantly more often with medial temporal structural lesions. Furthermore, there was a significant difference between concordance rates between sides of MRI lesions and EEG foci as a function of laterality: while the right-sided MRI lesions constantly showed ipsilateral EEG foci, EEG foci concurring with the left-sided MRI lesions proved to be often falsely lateralising. From these results, we assumed that lateral as well as medial temporal involvement is needed in the genesis of the psychic aura in contrast to the autonomic aura, which could be induced without lateral temporal involvement, and lesions in the left hemisphere are more apt to induce secondarily epileptogenic than those in the right hemisphere.

Adult↗
PubMed2003

Dementia accompanying motor neuron disease--7 cases.

Seven typical cases of dementia with motor neuron disease (D-MND) are reported. Among 1,000 dementia cases, D-MND was more frequent than Pick's disease, Lewy body disease or Creutzfeldt-Jakob disease. D-MND accounted for 30.4% of all forms of frontal lobe dementia (FLD) including FLD and Pick's disease. These data support that this combined syndrome may be more frequent than previously reported. As the subcortical neuropathology of D-MND is identical with MND, D-MND is rather the cortical manifestation of MND than a new disease entity.

Aged↗
PubMed2002

Joint proprioception before and after total knee arthroplasty.

To investigate the effects of total knee arthroplasty on joint proprioception, the absolute angular error of the knee in 38 consecutive patients before and after total knee arthroplasty for osteoarthritis and in 23 age-matched control subjects were examined. Varus and valgus laxity of the knee and muscle strengths of the thigh were measured using appropriate instruments. There were no significant differences in absolute angular error before and after total knee arthroplasty, independent of retaining or substituting the posterior cruciate ligament. The absolute angular error of the knee with a normal appearing anterior cruciate ligament was larger than that with a missing anterior cruciate ligament before total knee arthroplasty and decreased significantly after surgery. The absolute angular error correlated with the varus and valgus laxity of the knee, but did not correlate with the strength of thigh muscles after total knee arthroplasty. These results suggest that deficiency of the anterior cruciate ligament may not adversely affect proprioception in severe knee osteoarthritis. In addition, proper ligament balance may partly contribute to better proprioception after total knee arthroplasty.

Aged↗