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Biomedical subjects

T Hamada

Publications and source records attributed to T Hamada.

At least 145 records · Page 8Linked to original sources

[Effective melatonin therapy in a case of Machado-Joseph disease with insomnia].

The effects of melatonin (MLT) therapy on insomnia and serum MLT concentration were studied in a 44-year-old man with Machado-Joseph disease. He suffered from insomia since age 41, and could not sleep well, despite that he was given many kinds of hypnotics. He showed neither noctural central apnea, inspirative stridor, restless leg syndrome, REM without atonia, nor noctural polyuria, all of which are known to cause insomnia in spinocerebellar degeneration. The peak serum level of MLT was low, 9.2 pg/ml. He was administered 9 mg of MLT p.o. at 8 p.m., and it's peak noctural level elevated to 7,000 pg/ml, and this alleviated his intractable insomnia. Our experience indicate that the MLT could be effective for insomnia in MJD which relates to low MLT concentration.

Adult↗

[Carcinoma of the pancreatic head].

Focusing mainly on invasive ductal carcinoma of the pancreas, the history of radical surgery for this type of cancer is reviewed, including pancreatoduodenectomy, total pancreatectomy, extended radical surgery with main vascular resection and extended lymphadenectomy/retroperitoneal soft-tissue clearance, pylorus-preserving pancreaticoduodenectomy. In addition, duodenum-preserving pancreatic head resection, which has recently attracted attention in this field, as an operative technique for less-malignant, noninvasive intraductal papillary adenocarcinoma is also reviewed.

Anastomosis, Surgical↗

CTLA-4 gene polymorphism may modulate disease in Japanese multiple sclerosis patients.

Multiple sclerosis (MS) is widely believed to have a T-cell-mediated autoimmune etiology. The CTLA-4 gene is a strong candidate for involvement in autoimmune diseases because it plays an important role in the termination of T-cell activation. To examine the genetic association of the CTLA-4 gene locus with MS, we analyzed the CTLA-4 gene exon 1 A/G polymorphism in 74 Japanese MS patients and 93 controls. We also investigated the possible interactions of the CTLA-4 gene polymorphism with clinical course and severity, with MRI findings, with another genetic marker-HLA antigens, and with oligoclonal bands (OCB) in the cerebrospinal fluid (CSF). The CTLA-4 exon 1 polymorphism was similar between MS patients and controls. Conversely, clinical disability was significantly more severe in AA homozygous patients than in the other patients, and the allele frequency and the phenotype frequency of the A allele were significantly higher in patients with severe-grade MRI findings of cerebral white matter than in patients with mild-grade MRI findings. The allele frequency and the phenotype frequency of the A allele were significantly higher in patients with OCB than in patients without. This CTLA-4 polymorphism may modulate the prognosis of patients with MS and may be relevant to generation of OCB in the CSF.

Abatacept↗

Differential expression patterns of inositol trisphosphate receptor types 1 and 3 in the rat suprachiasmatic nucleus.

Inositol 1,4,5-trisphosphate receptor types 1 (IP(3)-R1) and 3 (IP(3)-R3) were found in the rat suprachiasmatic nucleus (SCN) and the levels of both of IP(3)-R1 and IP(3)-R3 mRNA showed a reciprocal circadian rhythm. IP(3)-R1 immunoreactive cells were localized in neuronal cells in the SCN. In contrast, IP(3)-R3 immunoreactive cells were mainly localized in the astrocytes in the ventrolateral region of the SCN. These results suggest that IP(3)-R1 and IP(3)-R3 may have differential roles in the SCN in the mammalian circadian rhythm.

Animals↗

Involvement of glutamate release in substance P-induced phase delays of suprachiasmatic neuron activity rhythm in vitro.

The suprachiasmatic nucleus (SCN) has been identified as a mammalian circadian rhythm clock. Treatment with substance P (SP) at zeitgeber time 13-14 produced phase delays of circadian rhythm in spontaneous neural activity in SCN neurons in vitro. SP-induced phase delays are blocked by treatment with not only SP receptor antagonist, spantide, but N-methyl-D-aspartate receptor antagonist, MK-801. In the biochemical experiment, we demonstrated that SP-induced glutamate release from the SCN slices was observed by the high-performance liquid chromatography assay. The present results suggest that glutamate release may be involved in SP-induced phase delays.

Animals↗

Shortened microsatellite d(CA)21 sequence down-regulates promoter activity of matrix metalloproteinase 9 gene.

One characteristic elements in the promoter of the matrix metalloproteinase 9 (MMP-9) gene is the d(CA) repeat. To investigate whether this element regulates the transcription of the MMP-9 gene and its enzymatic activities, we sequenced the promoter region isolated from esophageal carcinoma cell lines. TE9 cells with low MMP-9 enzymatic activity had the number of d(CA) repeats shortened from 21 to 14 or 18. TE8, TE10 and TE11 cells with high MMP-9 activities had 21 or 23 d(CA) repeats. Luciferase assays using MMP-9 promoter containing 18, 14 or 0 d(CA) repeats showed transcriptional activities which were 50, 50 or 5%, respectively, of the level achieved with promoter containing 21 d(CA) repeats. Sequence analysis of the promoter of 223 Japanese subjects revealed that most had two alleles with 20, 21 or 22 d(CA) repeats, whereas six had one or two alleles with 14, 18 or 19 d(CA) repeats. We postulate that length alteration of the d(CA) repeat causes phenotypic differences among carcinoma cells and that microsatellite instability may contribute to the polymorphism of d(CA) repeat length.

Base Sequence↗

A pitch glide activates an intermediate response between auditory N1 and mismatch negativity.

Pitch glides of a continuous tone elicit auditory N1-like responses. However, their characteristics have not well been investigated, and it remained unclear whether the response is an auditory true N1 or the mismatch negativity (MMN). We found here that a rapid pitch glide activates almost the same response as a true N1. On the contrary, as the rate of the pitch glide decreases, the response continuously varies the characteristics from true N1 to MMN. This suggests that there would exist intermediate responses between auditory N1 and MMN.

Acoustic Stimulation↗

Association of vitamin D receptor gene polymorphism with multiple sclerosis in Japanese.

1,25-Dihydroxyvitamin D3 (1,25(OH)2D3), the biologically active form of vitamin D, exerts an immunosuppressive effect and can completely prevent experimental autoimmune encephalomyelitis (EAE). 1,25(OH)2D3 exerts most of its actions only after it has bound to its specific nuclear receptors. To investigate the possible role of vitamin D receptor gene (VDRG) polymorphism in susceptibility to or disease-modulation of MS, we evaluated 77 Japanese patients with 'conventional' MS and 95 controls. A VDRG allelic polymorphism was assessed by Bsm1 endonuclease restriction after specific PCR amplification. Genotypic polymorphism was clearly defined as BB (absence of restriction site on both alleles), bb (presence of restriction site on both alleles), or Bb (heterozygous). We found overexpression of the b allele (92.9 vs. 84.2%: P=0.0138) and homozygote bb (85.7 vs. 71.6%; P=0.0263) in MS patients compared with controls. The results indicate for the first time an association of MS with VDRG polymorphism, which may be involved in pathogenesis of MS, or in the linkage disequilibrium of VDRG to another pathogenic gene loci. The role of VDR gene polymorphism should be further studied in other populations, and the distribution of other polymorphism, such as Apa I, Taq I, should be also analyzed to confirm another susceptibility gene for MS and to obtain more adequate strategies for treatment of MS.

Adolescent↗

The expression of the melatonin synthesis enzyme: arylalkylamine N-acetyltransferase in the suprachiasmatic nucleus of rat brain.

The hormone melatonin, secreted primarily from the pineal gland, plays an important physiological role in synchronizing biological rhythms and neuroendocrine. Presently, we find the expression of the serotonin N-acetyltransferase (arylalkylamine N-acetyltransferase, AA-NAT) mRNA, the rate-limiting enzyme in the conversion of serotonin to melatonin, in the rat suprachiasmatic nucleus (SCN) which contains the biological circadian clock in mammals. AA-NAT mRNA content in rat SCN did not show a significant circadian rhythm. However, AA-NAT enzyme activity was lowest at midday and highest at early night, and the rhythm persisted under constant dark conditions. These results indicate that the rat SCN is capable of synthesizing melatonin and suggest that melatonin synthesis in the SCN may be regulated by the circadian clock at the post transcriptional level.

Animals↗

Enhancement of cell adhesion and spreading by a cartilage-specific noncollagenous protein, cartilage matrix protein (CMP/Matrilin-1), via integrin alpha1beta1.

Cartilage matrix protein (CMP; also known as matrilin-1), one of the major noncollagenous proteins in most cartilages, binds to aggrecan and type II collagen. We examined the effect of CMP on the adhesion of chondrocytes and fibroblasts using CMP-coated dishes. The CMP coating at 10-20 micrograms/ml enhanced the adhesion and spreading of rabbit growth plate, resting and articular chondrocytes, and fibroblasts and human epiphyseal chondrocytes and MRC5 fibroblasts. The effect of CMP on the spreading of chondrocytes was synergistically increased by native, but not heated, type II collagen (gelatin). The monoclonal antibody to integrin alpha1 or beta1 abolished CMP-induced cell adhesion and spreading, whereas the antibody to integrin alpha2, alpha3, alpha5, beta2, alpha5beta1, or alphaVbeta5 had little effect on cell adhesion or spreading. The antibody to integrin alpha1, but not to other subunits, coprecipitated 125I-CMP that was added to MRC5 cell lysates, indicating the association of CMP with the integrin alpha1 subunit. Unlabeled CMP competed for the binding to integrin alpha1 with 125I-CMP. These findings suggest that CMP is a potent adhesion factor for chondrocytes, particularly in the presence of type II collagen, and that integrin alpha1beta1 is involved in CMP-mediated cell adhesion and spreading. Since CMP is expressed almost exclusively in cartilage, this adhesion factor, unlike fibronectin or laminin, may play a special role in the development and remodeling of cartilage.

Animals↗

Interhemispheric asymmetry of event-related fields concerned with logical processing during auditory oddball stimulation.

This study investigated the cortex during logical processing of auditory information using a 122-channel dc-SQUID gradiometer. The experimental task was designed to require a simple logical decision prior to counting rare paired tones, which consisted of two different pitches and were presented to separate ears. Among six subjects, left and right predominant dipolar activity was observed in three subjects each. When the dipolar sources were superimposed on MR images, the inferior region of the supramarginal gyrus showed activation, suggesting that logical processing occurred in the association cortex but not in the auditory cortex. We propose a modified cognitive sequence model in which auditory information processed in Heschl's gyri is transmitted to the supramarginal gyrus to commence automatic detection processing.

Acoustic Stimulation↗

The role of inositol trisphosphate-induced Ca2+ release from IP3-receptor in the rat suprachiasmatic nucleus on circadian entrainment mechanism.

Synchronization between the environmental lighting cycle and the circadian clock in the suprachiasmatic nucleus (SCN) is correlated with Ca2+ increase. The mechanism underlying the increase of Ca2+ and its relation to clock resetting are unknown. To address these issues, we examined the possibility whether inositol 1,4,5-trisphosphate receptor (IP3-R), which regulate intracellular Ca2+, was involved in the circadian rhythm component of the rat SCN. A novel IP3-induced Ca2+ release modulator, 2-amino-ethoxy diphenylborate (2APB), blocked optic nerve stimulation-induced neuronal field potentials in the SCN. Furthermore, glutamate-induced phase delay of the circadian firing pattern in the SCN was also blocked completely by 2APB in vitro. Together, these data suggest the possibility that IP3-induced Ca2+ release through IP3-R plays a role in the entrainment of the mammalian circadian clock, the SCN.

Animals↗

Diurnal regulation of a DNA binding protein to the period repeat sequence in the SCN nuclear extract of rat brain.

We previously reported the mammalian period repeat mRNA fluctuates during circadian time in the rat suprachiasmatic nucleus (SCN) which is considered to be a clock pacemaker in mammalian brain. Presently we discovered a period repeat sequence (PR) DNA-binding protein in the rat SCN nuclear extract. In the SCN, the binding activity of PR DNA-binding protein to (ACAGGC)3 was most highest during the late day and most lowest during the late night by electro-mobility shift assay (EMSA). In the cortex nuclear extract, the binding of PR DNA-binding protein did not show a significant variation during a day. This is the first report to show the existence of diurnal regulated PR DNA-binding protein in the SCN.

Animals↗

Overexpression of p21Waf-1 in vascular smooth muscle cells: regulation of proliferation, differentiation, and cell size.

Cyclin-dependent kinase inhibitor p21Waf-1 is recognized as a negative regulator of cell cycle progression, and it possibly mediates cell differentiation and apoptosis. To understand the role of p21Waf-1 in phenotypic modulation of vascular smooth muscle cells (SMC), we induced the overexpression of p21Waf-1 in cultured rat SMC. The recombinant adenovirus vector encoding p21Waf-1 (AdvCMVp21) was constructed by homologous recombination and the vector encoding beta-galactosidase (AdvCMVLacZ) was used as an experimental control. Administration of AdvCMVp21 suppressed serum-induced proliferation and cell cycle progression; however, the number of quiescent cells and the population of TUNEL-positive cells were not altered. Overexpression of p21Waf-1 did not affect the expression of contractile proteins and the availability of an endogenous growth factor signal p21Waf-1 may regulate cell cycle progression in SMC without affecting the apoptotic process and cell differentiation. Furthermore, the longitudinal diameter of AdvCMVp21 infected cells was increased compared with that of AdvCMVLacZ infected cells. Total protein content was also increased in AdvCMVp21 infected cells. Responses to the serum stimulation, proliferation and total protein synthesis may be independently regulated. Thus, the suppression of cell cycle progression by p21Waf-1 resulted in cellular hypertrophy of SMC.

Adenoviridae↗

Mosaicism of unstable CAG repeats in the brain of spinocerebellar ataxia type 2.

Spinocerebellar ataxia type 2 (SCA2) is caused by expansion of unstable CAG repeats within the coding region of the novel gene, ataxin-2, on chromosome 12q24.1. We analyzed CAG repeat size of the SCA2 allele in two deceased patients (father and daughter) to investigate the repeat mosaicism in CNS regions. The CAG repeat size was examined using lymphoblastoid cell lines, frozen brain tissues, and paraffin-embedded tissues. In each patient the major repeat size of the expanded allele varied within the brain or spinal cord (father, 39-42; daughter, 39-47 repeats), and was smaller by three to eight repeats in the cerebellum than in other CNS regions. Our results are in agreement with the findings in other polyglutamine disorders showing somatic mosaicism.

Adolescent↗

Immunohistochemical localization of fibroblast growth factor receptors in the rat mandibular condylar cartilage and tibial cartilage.

The fibroblast growth factor receptors (FGFRs), members of the tyrosine-kinase receptor family, are known to play a crucial role in the growth and development of cartilaginous tissues. The mandibular condylar cartilage has been suggested to have a characteristic growth pattern compared with the tibial growth plate cartilage, e.g., cell alignment, mode of proliferation and differentiation, and response to humoral and mechanical factors. To examine the mRNA expression and localization of fibroblast growth factor receptor (FGFR)-1, -2, and -3 in the condylar and tibial growth plate cartilages, reversed transcribed polymerase chain reaction (RT-PCR) assay and immunohistochemistry were carried out using growing rats. The enzymatically isolated rat condylar and tibial chondrocytes expressed mRNA of aggrecan and type II collagen, which are together known as the major cartilaginous extracellular matrices. Both types of cells expressed mRNA of FGFR-1, -2, and -3 by RT-PCR. In the neonatal rat, immunolocalization of FGFR-1, -2, and -3 was found in the middle of the condylar cartilage, mainly in the hypertrophic zone of the tibial cartilage. At 3 weeks old, the three FGFRs were broadly observed in both cartilages. At 8 weeks old, localization of FGFR-3 was absent in the hypertrophic cell layer of the condyle, whereas it was still broadly observed in the tibial growth plate cartilage. In the same stage, FGFR-1 and FGFR-2 showed similar localization in both cartilages to that at 3 weeks of age. All these observations suggest that FGFRs play an important role in the differential growth pattern of the condylar cartilage.

Animals↗

Late vasospasm of the inferior epigastric artery graft.

We report a case of vasospasm of a free inferior epigastric artery graft at 5-year angiographic follow-up after coronary artery bypass grafting. Although the cause of spasm was not clear, the graft was viable and had a vasoconstrictor profile similar to a gastroepiploic artery graft at long-term follow-up.

Coronary Angiography↗

Stabilizing record bases for edentulous obturator prostheses with silicone resilient relining material.

Stable record bases are critical for recording accurate maxillomandibular relations and in the evaluation of the esthetics and phonetics of wax trial prostheses. However, the record base for a maxillary obturator is often compromised because of a surgical defect and/or because the weight of the record base creates instability. This article describes a simple procedure for retaining and stabilizing a record base for an edentulous obturator prosthesis using silicone resilient relining materials.

Denture Liners↗