T Hamada

Hokkaido University, Sapporo-shi, Hokkaido, Japan

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Publications (278)521.06 Total impact

  • [show abstract] [hide abstract]
    ABSTRACT: The aim of this study was to investigate the effects of tandospirone on ataxia in various types of spinocerebellar degeneration (SCD). Fifteen milligram per day of tandospirone was administered to 39 patients with SCD (spinocerebellar atrophy (SCA) 1, five patients; SCA2, six patients; Machado-Joseph disease (MJD), 14 patient; SCA6, five patients; multiple system atrophy-cerebellar type (MSA-C), seven patients; and multiple system atrophy-Parkinson type (MSA-P), two patients). All patients were assessed before and 4 weeks after administration of the drug using the international cooperative ataxia rating scale total score (ARS), total length traveled (TLT) of body stabilometry, and a self-rating depression scale. Statistically, ARS showed a significant difference in MJD (p = 0.005) and SCA6 (p = 0.043). TLT also showed a significant difference in MJD (p = 0.002) and SCA6 (p = 0.043). Eight of 39 patients (SCA1, 1/5; SCA2, 0/6; MJD, 4/14; SCA6, 3/5; MSA-C, 0/7; and MSA-P, 0/2) showed more than a five point reduction in ARS, and 13 of 39 patients (SCA1, 0/5; SCA2, 1/6; MJD, 8/14; SCA6, 4/5; MSA-C, 0/7; and MSA-P, 0/2) showed a reduction of TLT. Our data indicate that the effects of tandospirone on ataxia are different between types of SCD. Therefore, tandospirone is useful for cerebellar ataxia in patients with MJD and SCA6.
    The Cerebellum 12/2010; 9(4):567-70. · 2.60 Impact Factor
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    ABSTRACT: The long term effect of either a salivary or a serum pellicle on Candida albicans biofilm formation on denture acrylic surfaces was investigated both by quantifying the ATP (adenosine triphosphate) content of the resultant biofilms and by scanning electron microscopy. When the biofilm formation on saliva-coated acrylic strips was examined, the yeasts initially colonised this surface at a slower rate than the controls although with increasing incubation time, at 72 h, the ATP content was almost ten-fold higher than the protein-free control strips. Ultrastructural studies revealed this to be due to cell aggregation and hyphal emergence, phenomena not observed in the controls. As compared with the control strips, biofilm activity of the serum-coated strips was almost 100-fold greater within 48 h incubation, and scanning electron microscopy revealed multilayer blastospore-blastospore co-adhesion, germ tube, hyphal and pseudohyphal emergence and blastospore-hyphal coadherence. Further immunocytochemical observation revealed that concanavalin-A binding material and fibronectin were involved in biofilm formation on both saliva and serum coated specimens and, in addition, mannan-binding protein and protein-A binding material also contributed to the biofilm formation on serum coated specimens.
    08/2009; 9(1):35-48.
  • Movement Disorders 08/2009; 24(13):2022-3. · 4.56 Impact Factor
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    ABSTRACT: This study investigates concanavalin A (ConA) as a novel factor that may enhance osteogenesis of mesenchymal stem cells (MSCs) in vitro. Various factors, such as cytokine bone morphogenetic protein-2 (BMP-2), have been studied for their possible promotion of MSC osteogenesis in vivo and in vitro. However, the factor that might be safer, more effective, and less expensive than these has not been determined. We therefore cultured human MSCs in osteogenic medium in the presence or absence of ConA, and used calcium assays to compare the effects of ConA and BMP-2 on MSC calcification. We also used enzyme-linked immunosorbent assay (ELISA) and quantitative polymerase chain reaction (PCR) to evaluate the expression levels of bone-specific markers. ConA and BMP-2 enhanced calcification with comparable effectiveness. The combination of ConA and BMP-2 further enhanced calcification slightly but significantly. ConA also increased osteocalcin and BMP-2 protein levels in MSC culture medium. Furthermore, ConA increased osteocalcin, RUNX2, BMP-2, BMP-4, and BMP-6 mRNA expression levels. However, the gene expression pattern of ConA-stimulated MSCs was different from that of MSCs stimulated by BMP-2. Together, these results suggest that ConA and BMP-2 enhance MSC osteogenesis via different pathways. ConA-induced bone formation in MSC cultures may be useful in regenerative medicine or tissue engineering in clinical studies, as well as in basic research on bone formation.
    The International journal of artificial organs 09/2008; 31(8):708-15. · 1.76 Impact Factor
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    ABSTRACT: Neck extensor muscle weakness and the dropped head sign are associated with various neuromuscular disorders. However, these symptoms are comparatively rare in myasthenia gravis (MG). We report a MG case that presented with dropped head sign as the main symptom. A 55-year-old man developed subacute weakness of the neck extensor muscle and presented with dropped head. We established a diagnosis of MG based on the results of an edrophonium test and a voluntary single fiber electromyogram (vSFEMG), and a high serum antiacetylcholine receptor antibody level. This patient was treated with pyridostigmine and his neurological symptoms improved. There are reported cases of dropped head sign as the first symptom of MG, however, in those cases, other muscles showed weakness during the first few months after onset. In the present case, throughout the clinical course no other symptoms outside of dropped head sign were seen.
    Internal Medicine 02/2007; 46(11):743-5. · 0.97 Impact Factor
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    ABSTRACT: Colonization of Candida albicans on oral surfaces can serve as a reservoir for disseminated infections, such as aspiration pneumonia and gastrointestinal infection, particularly in the immunocompromised host. Therefore, the aim of this study was to investigate the effects of salivary and serum pellicles on C. albicans, Streptococcus mutans, S. sanguis, Lactobacillus and Actinomyces colonization on type I collagen, a major organic component of periodontal ligaments. The colonization potential of two isolates each of C. albicans, S. mutans and S. sanguis, and a single isolate each of Lactobacillus and Actinomyces to uncoated (control), saliva-coated or serum-coated type I collagen plates (surface area 143 mm(2), Cell Disk; Sumitomo, Tokyo, Japan) was examined using a bioluminescent adenosine triphosphate assay based on firefly luciferase-luciferin system. The results revealed that with mutans streptococci, a saliva pellicle was significantly more effective in promoting bacterial colonization compared with the pellicle-free collagen disc, and the serum-coated sample significantly inhibited the colonization of streptococci (anova; P < 0b01). In contrast, in the case of C. albicans, Lactobacillus and Actinomyces isolates, a serum pellicle was significantly more effective in promoting the colonization, followed by saliva pellicle and uncoated specimen (anova; P < 0b01). These results suggested that crevicular fluid rich in seruminous components would promote the colonization of Candida, Lactobacillus and Actinomyces on type I collagen as opposed to streptococci which showed greater avidity to saliva-coated collagen.
    Journal of Oral Rehabilitation 11/2006; 33(10):767-74. · 2.34 Impact Factor
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    ABSTRACT: Apart from its unique lesion distribution pattern, the opticospinal form of multiple sclerosis (OSMS) is distinct among Japanese patients who satisfy the diagnostic criteria of MS. OSMS has been suggested to be strongly associated with HLA-DPB1*0501 in Japanese. However, association of DPB1*0301 with non-OSMS and lack of DPB1*0301 in OSMS were also reported. To verify the role of DPB1*0501 and DPB1*0301 in Japanese MS patients we determined the frequencies of these alleles in 26 patients with OSMS, 167 with non-OSMS and 156 normal subjects, who were all residents of Hokkaido, the northernmost island of Japan. All (100%) OSMS were negative for DPB1*0301 while 32 (19%) of the non-OSMS were positive for the allele. In DPB1*0301-negatives, the frequencies of DPB1*0501 in OSMS (85%) and non-OSMS (82%) were similar, but both were higher than in the controls (66%). In DPB1*0301-positives, the frequency of DPB1*0501 was low but similar in non-OSMS (12/32; 38%) and controls (6/14; 43%). Periventricular white matter lesions (PVL) were noted in 31 of 32 (97%) DPB1*0301-positive non-OSMS patients but in only 22 out of 135 (16%) DPB1*0301-negative non-OSMS patients and two out of 26 (8%) OSMS patients. Our findings indicate that DPB1*0501 plays an important role in the development of MS in general, but not in OSMS. The strong association of DPB1*0501 with OSMS may be due to the over-representation of the DPB1*0301 allele among individuals in the non-OSMS group. In addition, DPB1*0301 might be relevant to the development of periventricular lesions in Japanese patients with MS.
    Multiple Sclerosis 03/2006; 12(1):19-23. · 4.47 Impact Factor
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    ABSTRACT: The analysis of the adherence capacity of fungi to surfaces of both oral tissue and different tissues would be of interest in the fungal dissemination as an oral and systemic pathogen. We developed an in vitro adenosine triphosphate (ATP)-based assay technique to extract the cellular and fungal ATP separately, which allowed the quantitative evaluation of the adhesion of the yeast to monolayers of human gingival epithelial cells (GEC), gingival fibroblasts (GF) and pulmonary fibroblasts (PF). Seven oral isolates of Candida species (three of Candida albicans, three of Candida tropicalis and one of Candida glabrata) were used in the study. The adherent level of the Candida species varied depending on both the isolates and the cell origins, although all the Candida isolates had a significantly higher level of adherence to GEC than to GF except the single isolate of C. tropicalis. Whereas the adherent level of the five isolates to GEC was significantly higher than that to PF, the adherent level of the remaining two isolates of C. tropicalis to GEC was significantly lower than that to PF. These results suggest that candidal adherence to host tissue cells should be regulated in an isolate-dependent and cell-origin-dependent manner, and that the phenomena may be involved in the colonisation and/or dissemination of the fungi.
    Mycoses 02/2006; 49(1):14-7. · 1.28 Impact Factor
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    ABSTRACT: Clock genes, which mediate molecular circadian rhythms, are expressed in a circadian fashion in the suprachiasmatic nucleus and in various peripheral tissues. To establish a molecular basis for circadian regulation in the salivary glands, we examined expression profiles of clock-related genes and salivary gland-characteristic genes. Clock-related genes-including Per1, Per2, Cry1, Bmal1, Dec1, Dec2, Dbp, and Reverbalpha-showed robust circadian expression rhythms in the submandibular glands in 12:12-hour light-dark conditions. In addition, a robust circadian rhythm was observed in amylase 1 mRNA levels, whereas the expression of other salivary-gland-characteristic genes examined was not rhythmic. The Clock mutation resulted in increased or decreased mRNA levels of Per2, Bmal1, Dec1, Dec2, and Dbp, and in Cry1-/- background, Cry2 disruption also increased or decreased mRNA levels of these clock-related genes and the amylase 1 gene. These findings indicate that the Clock- and Cry-dependent molecular clock system is active in the salivary glands.
    Journal of Dental Research 01/2006; 84(12):1193-7. · 3.83 Impact Factor
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    ABSTRACT: ObjectivesAn alcohol-free tissue conditioner based on a n-butyl methacrylate/i-butyl methacrylate copolymer has recently been developed. The purpose of the present study was to compare some key properties of the new tissue conditioner with those of poly(ethyl methacrylate)-based conventional materials containing ethyl alcohol. The effect of a coating, which consisted of poly(ethyl methacrylate) and methyl methacrylate, was also evaluated.MethodsThe new alcohol-free tissue conditioner (Fictioner) and three tissue conditioners containing ethyl alcohol (FITT, Hydro-Cast, SR-Ivoseal) were evaluated. The coated alcohol-free material was also used. Gelation characteristics, dynamic viscoelastic properties and compatibility with dental stones were measured using a displacement rheometer, dynamic viscoelastometer and profilometer, respectively. In addition, weight changes during immersion in water were determined.ResultsThe working time and gelation time of the alcohol-free tissue conditioner were similar to those of the conventional materials. This alcohol-free material had significantly lower shear storage modulus and shear loss modulus, and higher loss tangent (P<0.05) than FITT and SR-Ivoseal at 0.01 and 1 Hz. The alcohol-free material maintained its inherent viscoelastic properties and exhibited only a slight change in weight during 14 days of water immersion when compared to the conventional materials. The application of the coating significantly reduced the loss of the initial viscoelastic properties and surface quality during the test periods.ConclusionsThe coated alcohol-free tissue conditioner would be superior to the conventional materials containing ethyl alcohol in view of viscoelastic properties after gelation, compatibility with dental stones and durability.—Reprinted with permission of Elsevier Publishing.
    The Journal of Prosthetic Dentistry. 01/2006;
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    ABSTRACT: New diagnostic criteria for multiple sclerosis (MS) were recently proposed from the international panel on the diagnosis of MS, and they include exclusion criteria, such as lesions extending over more than two vertebral segments on spinal MRI and CSF pleocytosis of more than 50/mm3. We reviewed the clinical features of 158 patients who satisfied the diagnostic criteria for MS except for having the above atypical paraclinical findings. All patients exhibited two or more clinical attacks and objective clinical evidence of multiple lesions without any evidence of other disorders. Thirty-three (20.9%) patients had one or both atypical paraclinical findings. Twenty-one out of the 33 patients were classified as having optico-spinal MS (OSMS), and the other 12 as non-OSMS patients with atypical large expanding or destructive cerebral, cerebellar or brainstem lesions on MRI as well as one or both atypical paraclinical findings. Based on this heterogeneity in clinical findings in MS, there is an urgent need to develop a common general concept of the "MS" syndromes, and the ethnic-related heterogeneity should be considered in the revised criteria for the diagnosis of MS.
    Journal of Neurology 08/2005; 252(7):824-9. · 3.58 Impact Factor
  • JAMA Neurology 06/2005; 62(5):834-5; author reply 835. · 7.58 Impact Factor
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    ABSTRACT: Formation of tissue conditioners is a process of polymer chain entanglements. This study evaluated the influence of composition and structure on dynamic viscoelasticity of concentrated polymer solutions based on poly(ethyl methacrylate) (PEMA) used as tissue conditioners through the sol-gel transition. The hypothesis was that the ethanol content is the most influential factor in determining gelation speed. Rheological parameters were determined with the use of a controlled-stress rheometer. Analysis of variance by orthogonal array L(16)(4(5)) indicated that the strong polar bonding of ethanol (contribution ratio rho = 53.8%; confirming the hypothesis) and molecular weight of polymer powders (rho = 26.7%) had a greater influence on the gelation times of PEMA-based systems than did the molar volume of plasticizers (rho = 9.0%) and concentration of polymers (i.e., powder/liquid ratio) (rho = 4.5%). The results suggest that the gelation of tissue conditioners based on PEMA can be controlled over a wide range by varying the polymer molecular weight, and especially ethanol content.
    Journal of Dental Research 05/2005; 84(4):376-81. · 3.83 Impact Factor
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    ABSTRACT: We investigated the polymorphisms of exon 1 (+49A/G) and promoter (-318C/T and -651C/T) regions of the CTLA-4 gene in 133 Japanese patients with conventional/classical multiple sclerosis (MS) and 156 healthy controls. Patients with optico-spinal MS (OSMS) or atypical clinical attacks were excluded from the study. There was no significant difference in the distribution of polymorphisms between patients and controls. Furthermore, there were no associations between polymorphisms and clinical characteristics, such as age at onset, disease prognosis, and HLA profiles. Our results suggest that CTLA-4 gene polymorphisms are neither conclusively related to susceptibility nor to the clinical characteristics of MS, especially in Japanese patients with conventional/classical form and clinical features identical to those of their counterparts in Western countries.
    Journal of Neuroimmunology 03/2005; 159(1-2):225-9. · 3.03 Impact Factor
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    ABSTRACT: Effective, pharmacologic approaches to the treatment of cerebellar ataxia are lacking or inadequate. We recently reported preliminary evidence that tandospirone citrate (tandospirone), a 5-HT1A agonist, improved cerebellar ataxia in patients with Machado-Joseph disease (MJD). In the course of that study, we found that such treatment also alleviated the pain associated with cold sensations in the legs, insomnia, anorexia, and depression, all of which are thought to be mediated through activation of the 5-HT1A receptor. In this paper, we reviewed the few published clinical trials that involved the use of 5-HT1A receptor agonists for the treatment of cerebellar ataxia, and discussed the current theories regarding their mechanism of action. Cortical cerebellar atrophy (CCA) was reported, in a double-blind study, to be amenable to treatment with tandospirone. Other types of spinocerebellar degeneration (SCD) i.e., olivopontocerebellar atrophy (OPCA) and Machado-Joseph disease (MJD) have also been reported to respond to the drug, but these have been small studies. Responsive patients exhibited only mild ataxia. The doses of 5-HT1A agonists that have been used successfully ranged from 12.5 mg/day to 60 mg/day (or 1 mg/kg), and were well tolerated by most patients.
    The Cerebellum 02/2005; 4(3):211-5. · 2.60 Impact Factor
  • International Congress Series 01/2005; 1284:213-214.
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    ABSTRACT: This study examined physical properties and compatibility with dental stones of two types of alginate impression materials. Five powder-type alginate impression materials (Alginoplast EM, Aroma Fine, Algiace Z, Coe Alginate, Jeltrate Plus) and a paste-type alginate impression material (Tokuso AP-1) were used. The dynamic viscosity immediately after mixing was measured by means of a controlled-stress rheometer. The gelation times were determined according to Japanese Industrial Standards (JIS) T6505, and recovery from deformation, strain in compression and compressive strength were determined according to the International Organization for Standardization (ISO) specification 1563. Detail reproduction and surface roughness of type III dental stones (New Plastone, New Sunstone) and a type IV dental stone (Die Stone) were evaluated using a ruled test block as specified in the ISO specification 1563 and a profilometer, respectively. The alginate impression materials evaluated in this study were all in compliance with the ISO specification 1563 and JIS T6505. The alginate impression materials had similar mechanical properties after gelation, whilst a wide range of dynamic viscosity immediately after being mixed, gelation times and compatibility with dental stones were found among the materials. The paste-type material had a higher dynamic viscosity and a shorter gelation time than the powder-type materials. The best surface quality was obtained with the paste-type material/type III dental stone cast combinations. The materials should be selected in consideration of initial flow, setting characteristics and compatibility with dental stones. The results suggested that a paste-type material would better meet the requirements of an alginate impression material.
    Journal of Oral Rehabilitation 12/2004; 31(11):1115-22. · 2.34 Impact Factor
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    ABSTRACT: Understanding the spectrum of idiopathic inflammatory demyelinating disorders (IIDD) is a fundamental issue for the diagnosis and treatment of these disorders as well as for the approach to their pathogenesis. The spectrum of IIDD is usually classified according to clinical course and lesion distribution. We compared the demographic features, clinical characteristics, laboratory findings, and genetic backgrounds between 193 Japanese patients with and without clinically or radiographically fulminant attacks who all satisfied the diagnostic criteria for multiple sclerosis (MS). "Fulminant attacks" in the current study represent attack-related clinically or radiologically severe relapses but do not necessarily mean severe disability. Patients with fulminant attacks were clinically and immunogenetically distinct from those free of such attacks, and the previously described characteristics of the opticospinal form of MS (OSMS) or neuromyelitis optica (NMO) were mostly shared by patients with fulminant attacks. HLA profiles were similar among patients with fulminant attacks irrespective of the lesion distributions. The GG homozygous and G alleles of the CTLA4 gene A/G coding SNP at position 49 in exon 1 were significantly more common in patients with fulminant attacks than in those without. Attack-related severity may be an important factor if validated by prospective studies defining criteria and establishing relationships to disease course and treatment regimens.
    Journal of the Neurological Sciences 11/2004; 225(1-2):71-8. · 2.24 Impact Factor
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    ABSTRACT: The effect of Lactobacillus reuteri against one of the major cariogenic organism, Streptococcus mutans, was studied. Yogurt products containing L.reuteri showed a significant growth inhibitory effect against S. mutans, whilst yoghurts with lactobaccilli other than L. reuteri did not show such inhibition. Further, double-blind, placebo-controlled trial demonstrated that consuming yogurt with L. reuteri significantly reduced the oral carriage of mutans streptococci, compared with the placebo yogurt.
    International Journal of Food Microbiology 10/2004; 95(2):219-23. · 3.43 Impact Factor
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    ABSTRACT: Peptide antibiotics are considered a new class of antifungal agents. Of these, an alpha-helical, cationic peptide termed Dhvar 4, a relative of salivary histatin has been shown to be an antifungal of relatively high potency. Similarly, lactoferricin B (LFB) and a derivative thereof, LFB(17-30), disrupts the fungal cell membrane and acts against Candida albicans. As Dhvar 4 and LFB(17-30), exhibit almost identical amino acid sequences at their C-terminal, we hypothesized that laboratory synthesis of peptides with an alpha-helical structure and having similar amphipathic properties could lead to products with candidacidal activity. Hence, three such peptides - JH8194, JH8195 and JH 8944, were synthesized and their antifungal properties compared with recognized antifungals LFB, LFB(17-30), human lactoferricin (LFH), Histatin-5 and Dhvar 4, against two isolates of C. albicans. The antifungal agents were synthesized and their secondary structures evaluated according to a previously described protocol of Situ and Bobek (2000)Antimicrob Agents Chemother44: 1485-1493. The C. albicans strains were oral isolates from a human immunodeficiency virus-infected (isolate A2) and a healthy (A6) individual. A standard concentration of yeasts was exposed to a range of dilutions of the agents for a specific duration and the cell death (viability) in terms of the resultant colony forming units ml(-1) was quantified. Dhvar 4, showed the most alpha-helical propensity, and was the least fungicidal while LFB and LFB(17-30) showed the highest antifungal potential, and demonstrated total kill of A6, and A2 at 5 and 10 microM concentrations, respectively whilst LFH killed both isolates at a l0 microM concentration. Of the three new synthetic peptides, JH 8194 was the most potent (total kill of A6/A2 strains at 1.25/2.5 microM), followed by JH 8195 (total kill of A6/A2 strains at 5/10 microM while JH 8944 was the least potent as a 25 microM concentration was required to kill either strain of Candida. On further analyses of the relationship between pI value of the peptides and their anticandicidal activity, a significant positive correlation was noted. In order to rule out a cytotoxic effect of the new synthetic peptides we compared the fungicidal and hemolytic activities under similar incubation conditions using freshly isolated erythrocytes and all three peptides exhibited no detectable hemolysis upto an concentration of 100 microM in contrast to the polyene antifungal amphotericin B that elicited significant initiation of hemolysis at a concentration of 5.0 microM. Our data suggest that laboratory synthesis of agents with an alpha-helical structure and having amphipathic properties similar to known, natural antifungal agents may be a promising avenue to generate products with improved antifungal activity.
    Oral Diseases 08/2004; 10(4):221-8. · 2.38 Impact Factor

Publication Stats

3k Citations
521.06 Total Impact Points


  • 1990–2010
    • Hokkaido University
      • Department of Neurology
      Sapporo-shi, Hokkaido, Japan
  • 1987–2010
    • Hokuyukai Neurological Hospital
      Sapporo, Hokkaidō, Japan
  • 1978–2008
    • Hiroshima University
      • • Department of Prosthetic Dentistry
      • • School of Dentistry
      Hiroshima-shi, Hiroshima-ken, Japan
  • 2002
    • Osaka University of Human Sciences
      Ōsaka, Ōsaka, Japan
  • 1994–2000
    • The University of Hong Kong
      • Faculty of Dentistry
      Hong Kong, Hong Kong
  • 1992–1998
    • Hokkaido University Hospital
      • Department of Radiology
      Sapporo, Hokkaidō, Japan
  • 1996–1997
    • Newcastle University
      Newcastle-on-Tyne, England, United Kingdom
    • Osaka University
      • Division of Brain Physiology
      Ibaraki, Osaka-fu, Japan
  • 1993–1997
    • Japan Red Cross Fukuoka Hospital
      Hukuoka, Fukuoka, Japan
  • 1989
    • University of Chicago
      • Department of Neurology
      Chicago, IL, United States