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Biomedical subjects

T Sugimoto

Publications and source records attributed to T Sugimoto.

At least 55 records · Page 3Linked to original sources

Testosterone increases osteoprotegerin mRNA expression in mouse osteoblast cells.

The role that androgens play in the regulation of bone metabolism has been substantiated in animals and humans. We previously demonstrated that testosterone inhibits osteoclast differentiation stimulated by parathyroid hormone through the androgen receptor in mouse bone-cell cultures. However, the details of this mechanism are still unknown. The present study was aimed at examining whether testosterone would affect the mRNA levels of osteoprotegerin (OPG) and receptor activator of Nf kappa B ligand (RANKL) in mouse bone-cell cultures as well as mouse osteoblastic cell-line, MC3T3-E1 cells by employing semi-quantitative RT-PCR. Testosterone increased OPG mRNA expression in both mouse bone-cell cultures and MC3T3-E1 cells. 10-8 M PTH-(1-34) as well as 10-8M 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] inhibited OPG mRNA expression in mouse bone cells. 10-8 M testosterone antagonized OPG mRNA expression inhibited by 10-8 M PTH-(1-34), but failed to affect OPG mRNA expression inhibited by 10-8 M 1,25(OH)2D3. 10-8 M alpha-dehydrotestosterone, a non-aromatizable androgen, increased OPG mRNA expression. On the other hand, testosterone did not affect RANKL mRNA expression in MC3T3-E1 or mouse bone cells. In conclusion, the present study demonstrated that testosterone increased OPG mRNA expression in mouse bone-cell cultures and the osteoblastic cell line. These effects are likely to take place through the androgen receptor.

Animals↗

Effects of electroconvulsive therapy on frontal white matter in late-life depression: a diffusion tensor imaging study.

This study was conducted to elucidate the effects of electroconvulsive therapy (ECT) on frontal white matter in late-life depressed patients. Diffusion tensor imaging was performed on 8 late-life depressed patients and 12 healthy age-matched controls. The patients were scanned before and after a course of ECT. Fractional anisotropy (FA) was determined in the frontal and temporal regions and the corpus callosum. A significant white matter FA reduction was found in widespread frontal and temporal brain regions in patients with depression before ECT treatment compared with controls. A significant increase in frontal white matter FA was seen following ECT treatment. A course of bilateral ECT ameliorated white matter integrity in frontal brain regions. This suggests a strong relationship with the antidepressant action of ECT.

Age of Onset↗

[Technical points of venous reconstruction for disorders of the superior vena cava].

In recent years, the number of patients with disorders of the superior vena cava due to mediastinal tumors such as malignant thymoma, teratoma and hilus type of lung cancer is now increasing in Japan. For those patients, we have tried to do venous reconstruction for the disorders of the superior vena cava (SVC) due to malignant mediastinal tumors. By these combined surgical procedures such as resection of malignant tumor and SVC reconstruction, curability and longevity of the life were apparently recognized. However, it is very important to select patients of which resection of tumor and venous reconstruction can be carried out by several kinds of examinations such as computed tomography (CT), magnetic resonance angiography (MRA) and venography. There are 3 kinds of reconstruction such as direct suture and patch grafting, as well as bypass grafting with ringed e-PTFE (expanded-polytetrafluoloethylene) prosthetic graft except for endovascular interventions of which number of patients is still few. On the other hand, bypass grafting is also effective for high intracranial pressure with syncope for the patients whose tumors could not be resected, because of huge tumor and diffuse invasion.

Blood Vessel Prosthesis↗

Pituitary adenylate cyclase-activating polypeptide-immunoreactive nerve fibers in rat and human tooth pulps.

The distribution of pituitary adenylate cyclase-activating polypeptide (PACAP) was examined in the tooth pulp. In rat and human tooth pulps, PACAP-immunoreactive (IR) nerve fibers were observed around blood vessels and in the subodontoblastic and odontoblastic layers. The predentine and dentine were devoid of such nerve fibers. The double immunofluorescence method indicated the co-expression of PACAP with calcitonin gene-related peptide (CGRP) or vasoactive intestinal polypeptide (VIP). Virtually all PACAP-IR nerve fibers co-expressed CGRP-immunoreactivity (IR) in the rat tooth pulp suggesting their sensory function. In addition, a retrograde tracing method indicated that PACAP-IR nerve fibers in the rat tooth pulp originated from the trigeminal ganglion. On the other hand, almost all PACAP-IR nerve fibers in the human tooth pulp co-expressed VIP-IR and, thus, thought to be autonomic in nature.

Animals↗

The co-expression of VR1 and VRL-1 in the rat vagal sensory ganglia.

Immunohistochemistry for two nociceptive transducers, the vanilloid receptor 1 (VR1) and vanilloid receptor 1-like receptor (VRL-1), was performed on the vagal sensory ganglia. In the jugular ganglion, VR1-immunoreactive (IR) neurons were small to medium-sized (range 49.7-1,125.6 microm(2), mean+/-S.D. 407.7+/-219.7 microm(2)), whereas VRL-1-IR neurons were medium-sized to large (range 223.6-1,341.1 microm(2), mean+/-S.D. 584.3+/-253.5 microm(2)). In the nodose ganglion, VR1- and VRL-1-IR neurons were mostly small to medium-sized (VR1: range 148.5-1464.4 microm(2), mean+/-S.D. 554.3+/-207.4 microm(2); VRL-1: range 161.7-1166.2 microm(2), mean+/-S.D. 541.9+/-186.2 microm(2)). The double immunofluorescence method revealed that co-expression of VR1-immunoreactivity among VRL-1-IR neurons was more abundant in the nodose ganglion (63%) than in the jugular ganglion (4%). The present study suggests that co-expression of VR1 and VRL-1 may be more common in visceral sensory neurons than in somatic sensory neurons.

Animals↗

Calcium-binding protein-immunoreactive innervation of the rat vibrissa.

Immunohistochemistry detected calcium-binding proteins (CaBPs) in corpuscular and Merkel nerve endings of the rat vibrissa. CaBP-immunoreactive (ir) corpuscular endings were divided into two types: ramified and unramified endings. Ramified endings were subdivided into reticular and Ruffini endings. Unramified endings were identical to longitudinal lanceolate endings which have been described previously. Reticular and unramified endings as well as Merkel endings co-expressed neurocalcin (NC)- and parvalbumin (PV)-immunoreactivity (ir). However, such endings were devoid of peptide 19 (PEP19)-ir. PV-ir Ruffini endings were immunoreactive for PEP19 but not NC. The retrograde tracing method revealed that 34, 21 and 18% of trigeminal neurons which project to the infraorbital nerve exhibited NC-, PEP19- and PV-ir, respectively. In addition, 73 and 36% of the PV-ir neurons showed NC- and PEP19-ir, respectively. The content and co-expression of CaBPs in vibrissal low-threshold mechanoreceptors may depend on their terminal morphology.

Animals↗

Regulatory regions and nuclear factors involved in nodule-enhanced expression of a soybean phosphoenolpyruvate carboxylase gene: implications for molecular evolution.

We have determined the genomic organization of two closely related phosphoenolpyruvate carboxylase genes in soybean, GmPEPC7, which is expressed at high levels in root nodules, and the housekeeping gene GmPEPC15. Their nucleotide sequences, including most introns and 5;-flanking regions within 600 bp upstream from the transcription start sites, are well conserved, suggesting that they were duplicated quite recently. To gain insights into the process of evolution of the tissue-specifically expressed GmPEPC7gene, we produced chimeric constructs carrying either the GmPEPC7or GmPEPC15promoter fused to the beta-glucuronidase gene. The expression patterns of the reporter observed in nodules that developed on transgenic hairy roots reflected the levels of mRNA levels produced by the genes in wild-type soybean plants, indicating that the GmPEPC7promoter directs nodule-specific expression. Loss-of-function experiments showed that the segment of GmPEPC7between -466 and -400, designated as the "switch region" (SR), was necessary for expression in nodules, although proteins that bind to SR were not detectable in a gel-retardation assay. Another gel-retardation assay indicated that putative nodule nuclear proteins bind specifically to the region of GmPEPC7between -400 and -318, designated as the "amplifier region" (AR). Both SR and AR have characteristic sequences that are not found in the GmPEPC15promoter. Furthermore, experiments using hybrid promoters derived from GmPEPC15demonstrated that AR confers high-level expression in nodules only in combination with SR. When wild-type soybean plants were subjected to prolonged darkness and subsequently illuminated, the level of GmPEPC7mRNA in nodules decreased and then recovered. This study suggests that the acquisition of two interdependent cis-acting elements resulted in molecular evolution of the nodule-enhanced GmPEPC7gene.

Base Sequence↗

The somatostatin sst2A receptor in the rat trigeminal ganglion.

Immunohistochemistry for the somatostatin sst2A receptor was performed on the rat trigeminal ganglion to know its function in the trigeminal nervous system. The immunoreactivity was detected in 9.4% of primary sensory neurons in the ganglion. These neurons were small to medium-sized (range=106.5-1123.2 microm(2); mean+/-S.D.=506.3+/-213.2 microm(2)) and predominantly located in the rostromedial part of the ophthalmo-maxillary division. They were also immunoreactive for calcitonin gene-related peptide and the vanilloid receptor subtype 1. In addition, 13.7% of trigeminal neurons which were retrogradely traced with fluorogold from the nasal mucosa exhibited sst2A receptor-immmunoreactivity. Trigeminal neurons which innervated the facial skin and tooth pulp were devoid of the immunoreactivity. In the brainstem trigeminal sensory nuclear complex, both the neuronal cell body and the neuropil exhibited sst2A receptor-immunoreactivity in the superficial medullary dorsal horn.The present study indicates that sst2A receptor-immunoreactive trigeminal nociceptors innervate the nasal mucosa. They may project to the superficial laminae of the medullary dorsal horn.

Animals↗

Genetic analysis on HLA loci in Japanese patients with abdominal aortic aneurysm.

PURPOSE: autoimmunity has been proposed as one of the pathogenesis of abdominal aortic aneurysm (AAA). There is also a likelihood that when aorto-iliac occlusive disease (AIOD) coexists with AAA, some other occlusive atherosclerotic diseases, such as ischemic heart disease and cerebrovascular disease, may develop, leading to a very poor long-term prognosis. Previous studies using serological HLA typing showed that HLA-DR15 was a risk factor for AAA. In this study, we performed HLA-DNA typing by PCR to clarify the relationship between AAA and HLA genotypes in Japanese patients with AAA. In addition, we analyzed whether HLA genotypes are involved in the pathogenesis of AIOD. RESULTS: we examined 78 HLA genotypes of class I (HLA-A and -B) and class II (HLA-DR) and found that 60.4 and 30.4% of 49 AAA patients had HLA-A2 and HLA-B61, respectively. These frequencies were significantly higher than those in control individuals (HLA-A2, p < 0.05; HLA-B61, p < 0.005). We also found that 55.6% of nine AAA patients with AIOD had both HLA-B52 and HLA-DR B1*1502. In contrast, only 10.0% each of 40 AAA patients without AIOD showed HLA-B53 or HLA-DR B1*1502. CONCLUSIONS: this study showed that HLA A-2 and HLA B-61, but not HLA DR-15, were important genetic risk factors for the development of AAA among the Japanese population. We also found high frequencies of HLA-B52 and HLA-DR B1*1502 in the AAA patients with AIOD than in those without, although this must be confirmed using a larger number of AAA patients with AIOD.

Aged↗

Effect of parathyroidectomy on bone mineral density in hemodialysis patients with secondary hyperparathyroidism: possible usefulness of preoperative determination of parathyroid hormone level for prediction of bone regain.

PURPOSE: To examine longitudinal changes of bone mineral density (BMD) after parathyroidectomy (PTx) in patients undergoing maintenance hemodialysis (HD) with severe secondary hyperparathyroidism (HPT) to determine which factor contributes most to bone changes. METHODS: Fifteen Japanese HD patients who had been refractory to medical therapy were subject to PTx with autotransplantation. We measured BMD by dual energy X-ray absorptiometry (DXA) at the lumbar spine (L2 - 4 BMD) and the distal 1/3 region of the radius (1/3R BMD) at 1, 3, 6, 12, 24, and 36 months after PTx. RESULTS: Baseline Z-score of BMD was markedly low at 1/3R (- 3.07) and slightly low at L2 - 4 (-0.59) in this group. A significant increase in L2 - 4 BMD was observed as early as one month after PTx, which was sustained afterwards. Annual percent changes in L2 - 4 and 1/3R BMD were + 15.6 % and + 6.4 %, respectively. The annual percent changes in BMD at both sites were positively associated with preoperative intact PTH levels (L2 - 4; r = 0.642, p = 0.010, 1/3R; r = 0.884, p < 0.001) and total alkaline phosphatase (ALP) levels (L2 - 4; r = 0.663, p = 0.007, 1/3R; r = 0.858, p < 0.001). Stepwise multiple regression analysis revealed that serum levels of intact PTH and ALP were the best predictors of both percentage and net changes in radial BMD with high determination coefficients (r 2 > 0.8). CONCLUSION: Successful PTx following appropriate supplementation with vitamin D and calcium provides a marked increase in lumbar BMD and a modest increase in radial BMD in HD patients with secondary HPT. Preoperative levels of PTH and ALP are useful for predicting postoperative changes in bone mass.

Absorptiometry, Photon↗

Central pontine myelinolysis associated with hypokalaemia in anorexia nervosa.

A 31-year-old man was admitted to hospital with of anorexia, binge eating, and self induced vomiting. On admission, he showed a pronounced low weight and disturbance of the body image and was diagnosed as having anorexia nervosa. In addition, electrolyte abnormalities, mainly hypokalaemia, and increased serum renin and aldosterone concentrations were recorded, suggesting pseudo-Bartter syndrome as a complication. Under frequent monitoring of the serum potassium and sodium concentrations, serum electrolytes were gradually corrected, but brain magnetic resonance imaging revealed reversible central pontine myelinolysis (CPM). Although attention has been mainly paid to the association of CPM with rapid correction of hyponatraemia and abnormal osmolality, this case report strongly suggested the involvement of hypokalaemia in the pathogenesis of CPM.

Adult↗

Magnetic semiconductor: structural, magnetic, and conducting properties of the salts of the 6-oxoverdazyl radical cation with M(dmit)(2) anions (M = Ni, Zn, Pd, and Pt, dmit = 1,3-dithiol-2-thione-4,5-dithiolate).

Five kinds of (1:1), (1:3), and (2:1) salts of 3-[4-(diethylmethylammonio)phenyl]-1,5-diphenyl-6-oxoverdazyl radical cation [V](+) with M(dmit)(2) anions (M = Ni, Zn, Pd, and Pt, dmit = 1,3-dithiol-2-thione-4,5-dithiolate) ([V](+)[Ni(dmit)(2)](-) (1), [V](+)[Ni(dmit)(2)](3)(-) (2), [V](+)(2)[Zn(dmit)(2)](2-) (3), [V](+)(2)[Pd(dmit)(2)](2-) (4), and [V](+)(2)[Pt(dmit)(2)](2-) (5)) and an iodide salt of [V](+) ([V](+)[I](-) (6)) have been prepared, and the magnetic susceptibilities (chi(M) values) have been measured between 1.8 and 300 K. The chi(M) of the (1:1) Ni salt (1) can be well reproduced by the sum of the contributions from (i) a Curie-Weiss system with a Curie constant (C) of 0.376 K emu/mol and a negative Weiss constant (theta) of -1.5 K and (ii) the one-dimensional Heisenberg antiferromagnetic alternating chain system with 2J(A-B)/k(B) = -274 K (alternation parameter alpha = J(A-C)/J(A-B) = 0.2). The chi(M) of the (1:3) Ni salt (2) can be well explained by the two-term contributions from (i) the Curie-Weiss system with C = 0.376 K emu/mol and theta = -5.0 K and (ii) the dimer system with 2J/k(B) = -258 K. The magnetic properties of 1 and 2 were discussed based on the results obtained by crystal structure analysis and ESR measurements of 1 and 2. The chi(M) values of the (2:1) Zn, Pd, Pt salts 3, 4, and 5 and [V](+)[I](-) salt 6 follow the Curie-Weiss law with C = 0.723, 0.713, 0.712, and 0.342 K emu/mol and theta = -2.8, -3.1, -2.6, and +0.02 K, respectively, indicating that only the spins of the verdazyl radical cation contribute to the magnetic property of these salts. The salts 1, 3, and 5 are insulators. On the other hand, the conductivity (sigma) of the Ni salt 2 and Pd salt 4 at 20 degrees C was sigma = 8.9 x 10(-2) and 1.3 x 10(-4) S cm(-)(1) with an activation energy E(A) = 0.11 and 0.40 eV, respectively. The salts 2 and 4 are new molecular magnetic semiconductors.

Journal Article↗

Effect of Brn-3a deficiency on nociceptors and low-threshold mechanoreceptors in the trigeminal ganglion.

Immunohistochemistry for protein gene product 9.5 (PGP 9.5, a neuron specific protein) and vanilloid receptor 1-like receptor (VRL-1, a marker for medium-sized to large primary nociceptors) were used to assess the effects of Brn-3a deficiency on neuronal innervation of oral tissues and neurons of the trigeminal ganglion (TG). In the knockout mouse, the number of PGP 9.5-immunoreactive (-ir) nerve fibers decreased in the facial cutaneous and oral mucous epithelia, as well as the incisor and molar tooth germs. The reduction of PGP 9.5-ir Merkel endings was also observed in some vibrissae. No obvious change was detected in other tissues. Cell size analysis demonstrated that the proportion of small neurons markedly increased while that of medium-sized and large neurons significantly decreased in the TG of the mutant. Moreover, Brn-3a deficiency caused the disappearance of TG neurons which were immunoreactive for VRL-1. Together, our data suggest that nociceptors and low-threshold mechanoreceptors with medium-sized to large cell bodies may be sensitive to the loss of Brn-3a.

Afferent Pathways↗

The co-expression of ASIC3 with calcitonin gene-related peptide and parvalbumin in the rat trigeminal ganglion.

The co-expression of ASIC3 with calcitonin gene-related peptide (CGRP) or parvalbumin (PV) was examined in the trigeminal ganglion (TG) by a double immunofluorescence method. ASIC3-immunoreactivity (IR) was detected in 23% of TG neurons. These neurons were of various sizes (range= 43-1768 microm(2), mean+/-S.D.=651+/-356 microm(2)); 26% and 14% of ASIC3-immunoreactive (IR) neurons co-expressed CGRP- and PV-immunoreactivity (IR), respectively; 33% and 13% of the TG neurons retrogradely labeled from the tooth pulp and facial skin, respectively, exhibited ASIC3-IR; 36% of CGRP-IR TG neurons which innervate these tissues co-expressed ASIC3-IR. Only 4% of ASIC3-IR cutaneous TG neurons showed PV-IR, while 25% of ASIC3-IR tooth pulp neurons were also immunoreactive for PV. The present study suggests that ASIC3-IR TG neurons supply the tooth pulp and facial skin with unmyelinated or finely myelinated axons. ASIC3-IR neurons which have large myelinated axons may be common in the tooth pulp but not the facial skin. The axonal morphology of ASIC3-IR TG neurons may depend on the variety of their receptive fields.

Acid Sensing Ion Channels↗