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Biomedical subjects

T Sugimoto

Publications and source records attributed to T Sugimoto.

At least 181 records · Page 10Linked to original sources

Vanilloid receptor 1-like receptor-immunoreactive primary sensory neurons in the rat trigeminal nervous system.

Immunohistochemistry for vanilloid receptor 1-like receptor (VRL-1), a candidate transducer for high-threshold noxious heat, was performed on rat trigeminal primary sensory neurons. The immunoreactivity was detected in 14% of the trigeminal ganglion cell bodies, while the neurons in the mesencephalic trigeminal tract nucleus were almost devoid of it (0.5%). The immunoreactive neurons in the trigeminal ganglion were mostly of medium to large size (mean+/-S.D. of 956+/-376microm(2)). Nerve bundles in the tooth pulp, periodontal ligament, facial skin and oral mucosa contained VRL-1-positive smooth nerve fibers. The immunoreactivity could not be traced to the isolated nerve fibers, except in the tooth pulp. In the brainstem trigeminal nuclear complex, a notable concentration of the immunoreactivity was seen in laminae I and II of the medullary dorsal horn. Thirty-seven per cent of the trigeminal ganglion neurons retrogradely labeled from the tooth pulp exhibited VRL-1 immunoreactivity, while the immunoreactivity was detected in only 9% of those labeled from the skin. Co-expression of calcitonin gene-related peptide was common among the VRL-1-immunoreactive tooth pulp neurons (45%) and cutaneous neurons (25%). Moreover, as many as 41% of the VRL-1-immunoreactive tooth pulp neurons co-expressed parvalbumin immunoreactivity. Parvalbumin immunoreactivity was never detected in the VRL-1-immunoreactive cutaneous neurons. From the findings of the present study, we propose that large primary neurons responding to high-threshold noxious heat are abundant in the tooth pulp, but not in the facial skin.

Animals↗

Treatment of osteopenia secondary to primary hyperparathyroidism.

A major challenge in the management of primary hyperparathyroidism (pHPT) is the decision regarding which patients should undergo parathyroidectomy (PTX). although the Consensus Development Conference of the National Institutes of Health (NIH) has proposed guidelines for the indication of surgery. We found that PTX brings about increases in radial and lumbar BMD values as high as 10% in virtually all pHPT patients including postmenopausal women and those without an indication for surgery based on NIH criteria. Serum alkaline phosphatase (ALP) level and the severity of cortical bone mass reduction are clinically useful for predicting the changes in lumbar BMD after PTX. The present findings provide a useful clue for the indication of surgery in pHPT, and seem to warrant a more extended indication than that of the NIH. We also described the recent progress in studies on calcium-sensing receptor (CaR), and discussed the possibility of bone mass recovery by medical treatment of pHPT with a newly introduced CaR agonist ('calcimimetics').

Absorptiometry, Photon↗

Lipophilization of lysozyme by short and middle chain fatty acids.

Hen egg white lysozyme was lipophilized with short and middle chain saturated fatty acids (caproic, capric, or myristic acid). The yield, bactericidal properties, and structural properties of lipophilized lysozymes were investigated. The yield of lipophilization of lysozyme greatly increased with the decrease in the chain length of fatty acid. Lipophilization broadened the bactericidal action of lysozyme to Gram-negative bacteria with little loss of enzymatic activity. The bactericidal activity increased in proportion to the number of bound short chain fatty acids. The thermal stability of lipophilized lysozyme decreased in proportion to the chain length and number of bound fatty acids.

Animals↗

Domain-specific mutations in TGFB1 result in Camurati-Engelmann disease.

Camurati-Engelmann disease (CED, MIM 131300) is an autosomal dominant, progressive diaphyseal dysplasia characterized by hyperosteosis and sclerosis of the diaphyses of long bones. We recently assigned the CED locus to an interval between D19S422 and D19S606 at chromosome 19q13.1-q13.3, which two other groups confirmed. As the human transforming growth factor-1 gene (TGFB1) is located within this interval, we considered it a candidate gene for CED.

Base Sequence↗

Long-term molecular remission induced by donor lymphocyte infusions for recurrent acute myeloblastic leukemia after allogeneic bone marrow transplantation.

A case of acute myelogenous leukemia with a t(8;21) translocation relapsed 5 months after allogeneic bone marrow transplantation (allo-BMT). After chemotherapy-induced hematologic remission, the patient received donor lymphocyte infusions (DLI); 4.9 x 108/kg T cells were infused. After DLI, she achieved molecular CR for the first time after allo-BMT, which lasted for 40 months. However, she suffered from grade III acute GVHD of the skin and the liver. Hepatic GVHD was sustained and resulted in fatal outcome. The case demonstrates that DLI is a double-edged sword. Further study is necessary before DLI can be considered to be a beneficial therapy for acute leukemia. Bone Marrow Transplantation (2000) 26, 809-810.

Adult↗

The impact of a catastrophic earthquake on morbidity rates for various illnesses.

It has been reported that some natural catastrophes increase morbidity rates for illness. In this study, we investigated the impact of the 1995 Hanshin-Awaji earthquake on morbidity rates for various illnesses by analysis for correlations between the extent of damage due to the earthquake and occurrences of various illnesses. We searched the medical records of 1948 patients hospitalized due to illness in 48 hospitals during the first 15 days after the earthquake. In each of 14 affected areas, the hospital admission rate and estimated morbidity ratio for each illness were calculated. Destruction ratios were determined based upon the number of dwellings completely destroyed in each area. For total illnesses and each major illness, linear regression analyses were performed comparing hospital admission rates, estimated morbidity ratios, and destruction ratios. Hospital admission rates and estimated morbidity ratios among the 1948 patients were significantly correlated to destruction ratios. With pneumonia, dehydration, acute heart failure, asthmatic attack, and peptic ulcer, hospital admission rates and estimated morbidity ratios were significantly related to destruction ratios, while no significant correlations between estimated morbidity ratios and destruction ratios existed for cerebral vascular disease or ischemic heart disease. Peptic ulcer and pneumonia showed especially high correlation values (age- and sex-adjusted R2>0.7). The present study revealed a strong link between the extent of damage due to the catastrophic earthquake and an increase in morbidity rates for acute illnesses, especially peptic ulcer and pneumonia.

Adolescent↗

Role of mitogen-activated protein kinases as downstream effectors of transforming growth factor-beta in mesangial cells.

Transforming growth factor-beta (TGF-beta) is a multifunctional cytokine that regulates cell proliferation, differentiation, and production of extracellular matrix proteins in various types of cells including mesangial cells. Although TGF-beta has been also known as an important player in the pathogenesis of various fibrotic diseases including glomerulosclerosis, signal-transduction cascades of TGF-beta have remained to be clarified. However, emerging evidence indicates that TGF-beta can activate various signal transduction cascades such as Smad proteins and mitogen-activated protein kinases (MAPKs) in many types of cells. Here, we examine the role of MAPKs in TGF-beta-induced gene expression of extracellular matrix proteins in mesangial cells. TGF-beta increases extracellular signal-regulated kinase (ERK) activity, one of the MAPKs, and the expression of fibronectin mRNA and protein in rat mesangial cells. Furthermore, PD98059, a specific inhibitor of MAPK/ERK kinase (MEK), can inhibit this TGF-beta-induced fibronectin expression. These data suggest that MAPKs play an important role in TGF-beta-mediated extracellular matrix production in mesangial cells.

Animals↗

Improved survival for patients with advanced neuroblastoma after high-dose combined chemotherapy based in part on N-myc amplification.

BACKGROUND/PURPOSE: In spite of many different kinds of chemotherapy for neuroblastoma, the prognosis for advanced neuroblastoma remains unsatisfactory. In particular, the outcome of advanced neuroblastoma with high copies of the N-myc gene tend to be poor. Therefore, the new high-dosage combined chemotherapy regimens for advanced neuroblastoma based in part on the N-myc amplification status has been utilized in the Kyushu area of Japan since 1991. This study aims to investigate whether these new regimens based in part on N-myc amplification have improved the survival rate of stage III and stage IV patients in comparison with the old regimens. METHODS: Between 1983 and 1995, 77 patients over 1 year of age and with stage III or IV neuroblastoma were registered in the Kyushu Area. Between 1983 and 1990, 49 patients received 1 of 2 combined chemotherapy regimens consisting of cyclophosphamide, cisplatin plus VM-26, and Adriamycin plus DTIC. Since 1991, two new regimens (New A1 and A3) have been administered based on the N-myc amplification status in a total of 28 patients. The New A1 regimen, which consists of cyclophosphamide, cisplatin, Adriamycin, and VP-16 has been administered in cases of less than 10 copies of N-myc, whereas the A3 regimen, consisting of a higher dose of cyclophosphamide, cisplatin, Adriamycin, and VP-16, has been administered in cases of more than 10 copies of N-myc. The survival rate was then compared between the old regimens and the new regimens. RESULTS: The 3-year survival rate (61.5%) for patients treated by the new regimens was significantly higher than that (32.7%) for patients treated by the old regimens (P <.01). Regarding the 24 cases of more than 10 copies of N-myc, the 3-year survival rate (35.9%) of the 13 patients treated by the A3 regimen was higher than that (0%) of the 11 patients treated by the old regimens (P <.05). However, in the 19 stage IV patients treated by the new regimens, the 3-year survival rate (11.1%) of the 9 cases of more than 10 copies was significantly lower than that (77.8%) of the 10 cases of less than 10 copies of N-myc (P <.01). CONCLUSIONS: These results suggest that high-dose combined chemotherapy based in part on the N-myc amplification status significantly improved the prognosis of patients with advanced neuroblastoma. However, stage IV patients with N-myc amplification still require a more effective treatment modality.

Antineoplastic Combined Chemotherapy Protocols↗

Quantitation of Fas and Fas ligand gene expression in human ovarian, cervical and endometrial carcinomas using real-time quantitative RT-PCR.

Alterations in the expression of Fas (CD95/APO-1) and its ligand (FasL) have been demonstrated in various types of cancers as a mechanism for tumour cell to escape from the immune system. In the present study, we evaluated the expression of the Fas and FasL genes in a wide range of primary gynaecological carcinomas. These included 31 ovarian, 29 cervical and 25 endometrial carcinoma tissues as well as four ovarian and three cervical carcinoma cell lines. Our real-time quantitative reverse transcription polymerase chain reaction analysis revealed that down-regulation of Fas expression is more prominent than the up-regulation of FasL expression in all types of gynaecological cancer studied. This down-regulation of Fas expression was also true for the seven carcinoma cell lines. Only one cervical carcinoma cell line, DoT, exhibited a high level of FasL expression. These results indicated that down-regulation of Fas expression is a common abnormality in many types of cancers including gynaecological cancers, whereas an increase in FasL expression is not a common phenomenon in these cancers.

Cervix Uteri↗

Association between parathyroid hormone (PTH)/PTH-related peptide receptor gene polymorphism and the extent of bone mass reduction in primary hyperparathyroidism.

Genetic contributions to bone mineral density (BMD) and bone turnover are well known. In the present study, we analyzed the relationship between polymorphism of parathyroid hormone (PTH)/PTH-related peptide (PTHrP) receptor gene existing in exon M7 and the clinical characteristics of primary hyperparathyroidism (pHPT). PTH/PTHrP receptor genotypes were analyzed in 92 pHPT patients by direct sequence to determine whether nucleotide 1417 of the cDNA was C or T. BMD levels at the lumbar spine and at the radius before and one year after parathyroidectomy, as well as serum levels of calcium, phosphorus, alkaline phosphatase (ALP) and intact PTH were measured. Although there were no significant differences in serum levels of calcium, phosphorus and intact PTH, ALP was significantly lower in the CT genotype compared with the TT genotype. BMD level at the radius was significantly higher in the CT genotype than in the CC genotype. Moreover, an increase in radial BMD one year after parathyroidectomy was significantly less in CT genotype than two other genotypes (CC, TT). The present study is the first to indicate that the polymorphism of PTH/PTHrP receptor gene is closely related to the extent of bone mass reduction in pHPT and that this polymorphism would be one of the genetic factors responsible for the severity of the pathological state of pHPT.

Alkaline Phosphatase↗

The characteristics of mediastinal neuroblastoma.

The prognosis of mediastinal neuroblastoma has been reported to be better than for other neuroblastomas. The reason for this is however not clear. Furthermore, a comparison between mediastinal neuroblastoma and the other neuroblastomas has been rarely reported so far. In this study, the characteristics of mediastinal neuroblastoma (84 cases) are investigated and compared with those of other neuroblastomas (440 cases). Regarding clinical factors, the age distribution and the rate of cases detected at mass screening were similar in both groups. According to Evan's staging system, the rates of early stage (I, II) were 62% in the mediastinal neuroblastoma and 38% in the other neuroblastomas (p<0.001). Regarding the biological prognostic factors, a favorable histology based on Shimada's classification was found in 100% (35/35) of the mediastinal neuroblastoma cases and in 85% (112/132) of the other neuroblastoma cases (p<0.05). With regard to N-myc amplification, all of the examined 42 cases in mediastinal neuroblastoma had a N-copy number of less than 10 copies, while 32 of the examined 263 cases (12%) in the other neuroblastomas had an amplification of N-myc of more than 10 copies (p<0.05). The 5-year survival rates were 78% in the mediastinal neuroblastoma and 59% in the other neuroblastomas, respectively. Of the cases who underwent an incomplete resection of primary tumors in localized neuroblastoma, the 5-year survival rate of the mediastinal neuroblastoma cases was significantly more favorable than that of the other neuroblastomas. The majority of mediastinal neuroblastoma cases showed an early stage and favorable prognostic factors. It is likely that the clinical and biological prognostic factors of the tumor are therefore more closely correlated with the outcome of mediastinal neuroblastoma rather than the degree of the surgical resection. Regarding the treatment for mediastinal neuroblastoma, it is most important to evaluate the biology of the tumor after surgical resection.

Child, Preschool↗

Relationship between cystic change and rotatory vertigo in patients with acoustic neuroma.

Acoustic neuromas are benign neoplasms that most often arise from the vestibular nerve. Many patients with this tumor experience some degree of vestibular symptoms. However, patients rarely complain of rotatory vertigo. Acoustic neuromas are known to exhibit a cystic appearance in some patients. It was hypothesized that cystic change might be a causative factor for rotatory vertigo. A retrospective study of 178 patients with unilateral acoustic neuroma who underwent surgery in the Department of Otolaryngology at Tokyo Medical and Dental University was carried out. The cystic appearance of the tumors was detected preoperatively by magnetic resonance imaging and confirmed at surgery. The relationship between cystic change of the tumor and presentation with rotatory vertigo was examined. Of the 178 patients studied, only 10 had both cystic change of the tumor and rotatory vertigo, and 120 had neither cystic tumor nor rotatory vertigo. Of the remaining 48 patients, 24 experienced rotatory vertigo with negative findings for cystic tumor and the other 24 had evidence of cystic tumor but no rotatory vertigo. Tumor with cystic change was observed in 34 patients, accounting for 19.1% of all patients studied. Rotatory vertigo was also experienced in 34 patients (19.1%). Of the 34 patients with cystic lesions, 29.4% (10) had rotatory vertigo. The difference in percentage of the two groups did not reach statistical significance. It is suggested that there may be other factors causing rotatory vertigo in patients with acoustic neuromas than cystic change of the tumor.

Acute Disease↗

Pharmacodynamic analysis between plasma level and inhibition of acid output after administration of a new histamine H2-receptor antagonist (Z-300) in dog.

1. The relationship between plasma levels of a new H2-receptor antagonist, Z-300, and an active sulphoxide metabolite, and inhibitory effects on gastric acid secretion after intravenous or oral administration to dog have been examined. After both routes of administration, Z-300 in plasma eliminated with two phases, and the terminal half-lives were approximately 2 h. The level of sulphoxide in plasma reached a maximum at 0.6-0.7 h after administration, then subsequently eliminated with a half-life of approximately 6 h. 2. The maximal pharmacological effect of inhibition of gastric acid secretion (90-91%) was observed at 2 h (i.v.) and 6 h (p.o.), and the action persisted until 7 h after administration. 3. Since there was no correlation between plasma levels of Z-300 and pharmacological effects, the pharmacological effects were calculated by pharmacodynamic model including the effect compartment. The inhibition of acid output could be calculated by the amounts of Z-300 and sulphoxide corrected by pharmacological efficacy in the effect compartment. 4. These findings suggest that Z-300 contributes to the rapid appearance of the pharmacological effects in dog, whereas the sulphoxide, which eliminates slowly in plasma, contributes to duration.

Acetamides↗

Treatment of childhood acute myelogenous leukemia with allogeneic and autologous stem cell transplantation during the first remission: a report from the Kyushu-Yamaguchi Children's Cancer Study group in Japan.

A total of 64 newly diagnosed acute myelogenous leukemia patients (except FAB M3 and/or Down syndrome) under 18 years of age were consecutively enrolled into the study. Patients having an HLA-identical sibling (allo group) were assigned to undergo allogeneic bone marrow transplantation (allo BMT) in the first complete remission (CR). Others (non-allo group) were assigned to undergo autologous peripheral blood stem cell transplantation (PBSCT) or autologous BMT (auto BMT). Conditioning regimen was busulfan + melphalan for all transplantation. Of 64 patients (allo group 24; non-allo group 40), 59 (92.2%) achieved a CR. Eighteen relapses occurred (allo group 4; non-allo group 14) and 6 died during the first CR. The 5-year event-free survival (EFS) rate was 53.3 +/- 6.4% at a median follow-up period of 45 months. The 5-year EFS rates of allo and non-allo groups were 70.8 +/- 9.3% and 43.0 +/- 8.1%, respectively (p = .08). The EFS rates at 5 years post-transplant for allo BMT from an HLA-identical sibling (n = 18), PBSCT (11), and auto BMT (6) were 88.1 +/- 7.9%, 41.6 +/- 19.7%, and 83.3 +/- 15.2%, respectively. The outcome of allo BMT was superior to that of autograft. Auto BMT rather than PBSCT might contribute to a long-term survival in case of no available HLA-identical siblings.

Adolescent↗

Gene expressions of leptin, insulin receptors and lipogenic enzymes are coordinately regulated by insulin and dietary fat in rats.

Regulation of the gene expressions of leptin, insulin receptors and lipogenic enzymes was investigated after refeeding a fat-free diet or a 10 g/100 g corn oil diet to food-deprived rats. Plasma glucose and insulin concentrations began to increase 30 min after the feeding and further increased up until 8 h. In these rats, the expression of leptin mRNA in adipose tissue began to increase significantly only 30 min after feeding, and reached a maximum at 8-16 h. However, plasma leptin levels did not increase until 4 h after refeeding, then markedly increased and reached the maximal level after 8 h. The expression of leptin mRNA and plasma leptin concentrations generally were greater in rats fed the corn oil diet compared to those fed the fat-free diet. Insulin receptor mRNA concentrations in the liver and adipose tissue began to decrease 30 min after the refeeding, in contrast to the plasma insulin increase, and continued to decrease until 8 h. The expression of acetyl-CoA carboxylase and fatty acid synthase mRNA began to increase 4-8 h after feeding and reached maximal levels at 16-24 h. Leptin treatment suppressed the expression of lipogenic enzyme mRNA in rats fed the fat-free diet but not in corn oil-fed rats, in which the expression was suppressed by polyunsaturated fatty acids and leptin expression was higher. Thus, we suggest that the glucose and insulin-dependent expressions of leptin, insulin receptors and lipogenic enzymes are coordinately and/or mutually regulated by dietary manipulation.

Acetyl-CoA Carboxylase↗

Amelioration of accelerated diabetic mesangial expansion by treatment with a PKC beta inhibitor in diabetic db/db mice, a rodent model for type 2 diabetes.

Activation of protein kinase C (PKC) is implicated as an important mechanism by which diabetes causes vascular complications. We have recently shown that a PKC beta inhibitor ameliorates not only early diabetes-induced glomerular dysfunction such as glomerular hyperfiltration and albuminuria, but also overexpression of glomerular mRNA for transforming growth factor beta1 (TGF-beta1) and extracellular matrix (ECM) proteins in streptozotocin-induced diabetic rats, a model for type 1 diabetes. In this study, we examined the long-term effects of a PKC beta inhibitor on glomerular histology as well as on biochemical and functional abnormalities in glomeruli of db/db mice, a model for type 2 diabetes. Administration of a PKC beta inhibitor reduced urinary albumin excretion rates and inhibited glomerular PKC activation in diabetic db/db mice. Administration of a PKC beta inhibitor also prevented the mesangial expansion observed in diabetic db/db mice, possibly through attenuation of glomerular expression of TGF-beta and ECM proteins such as fibronectin and type IV collagen. These findings provide the first in vivo evidence that the long-term inhibition of PKC activation in the renal glomeruli can ameliorate glomerular pathologies in diabetic state, and thus suggest that a PKC beta inhibitor might be an useful therapeutic strategy for the treatment of diabetic nephropathy.

Albuminuria↗

Evidence of protein synthesis during resuscitation of ischemically damaged canine pancreas by the two-layer method.

The two-layer method, which supplies sufficient oxygen to the canine pancreas graft and allows adenotriphosphate synthesis within the graft, resuscitates the ischemically damaged pancreas graft during mild hypothermic (20 degrees C) preservation, but the mechanisms are unknown. The purpose of this study was to determine whether protein synthesis was performed on ischemically damaged pancreas graft during preservation by the two-layer method in a canine autotransplantation model. The pancreas grafts subjected to 90 minutes of warm ischemia were preserved by the two-layer method (perfluorochemical/University of Wisconsin solution) at 20 degrees C for 5 hours. Graft viability was judged from graft survival after autotransplantation. DNA, RNA, and protein synthesis was quantitated by determining incorporation of tritiated thymidine, tritiated uridine, and tritiated leucine, respectively, during preservation. Significant increases in RNA and subsequent protein syntheses were observed during preservation by the two-layer method. In contrast, DNA synthesis did not follow RNA and protein synthesis. We conclude that protein is synthesized in the process of postischemic cellular recovery of the pancreas graft during mild hypothermic preservation by the two-layer method.

Animals↗