Biomedical subjects

T Goto

Publications and source records attributed to T Goto.

At least 55 records · Page 3Linked to original sources

PubMed2003

Effects of static magnetic fields on bone formation in rat osteoblast cultures.

Although the promotional effects on osteoblasts of pulsed electromagnetic fields have been well-demonstrated, the effects of static magnetic fields (SMF) remain unclear; nevertheless, magnets have been clinically used as a 'force source' in various orthodontic treatments. We undertook the present investigation to study the effects of SMF on osteoblastic differentiation, proliferation, and bone nodule formation using a rat calvaria cell culture. During a 20-day culture, the values of the total area and the number and average size of bone nodules showed high levels in the presence of SMF. In the matrix development and mineralization stages, the calcium content in the matrix and two markers of osteoblastic phenotype (alkaline phosphatase and osteocalcin) also showed a significant increase. Accordingly, these findings suggest that SMF stimulates bone formation by promoting osteoblastic differentiation and/or activation.

Alkaline Phosphatase↗

PubMed2003

A case of anaphylactoid shock induced by the BS polysulfone hemodialyzer but not by the F8-HPS polysulfone hemodialyzer.

A 57-year-old woman was admitted because of severe bradycardia and hypotension caused by an anti-arrhythmic agent and beta-blocker. For 19 months before admission, she had been undergoing hemodialysis with an F8-HPS polysulfone membrane hemodialyzer without any complications. In 2 dialysis sessions after admission, when a BS polysulfone membrane was used, she experienced anaphylactoid shock with severe hypotension leading to syncope, dyspnea and vomiting, just after the start of hemodialysis. After the anaphylactoid shock, her dialyzer membrane was changed to a cellulose triacetate membrane and she did not suffer from such attacks. This case indicates that severe anaphylactoid shock may be caused by a biocompatible dialyzer membrane and that the reactions of patients to each polysulfone membrane may differ among polysulfone membranes made by different manufacturers.

Anaphylaxis↗

PubMed2002

Developmental regulation of the effects of fibroblast growth factor-2 and 1-octanol on neuronogenesis: implications for a hypothesis relating to mitogen-antimitogen opposition.

Neocortical neurons arise from a pseudostratified ventricular epithelium (PVE) that lies within the ventricular zone (VZ) at the margins of the embryonic cerebral ventricles. We examined the effects of fibroblast growth factor-2 (FGF-2) and 1-octanol on cell output behavior of the PVE in explants of the embryonic mouse cerebral wall. FGF-2 is mitogenic and 1-octanol antimitogenic in the PVE. Whereas all postmitotic cells migrate out of the VZ in vivo, in the explants some postmitotic cells remain within the VZ. We refer to these cells as the indeterminate or I fraction, because they neither exit from the VZ nor reenter S phase as part of the proliferative (P) fraction. They are considered to be either in an extremely prolonged G(1) phase, unable to pass the G(1)/S transition, or in the G(0) state. The I fate choice is modulated by both FGF-2 and 1-octanol. FGF-2 decreased the I fraction and increased the P fraction. In contrast, 1-octanol increased the I fraction and nearly eliminated the P fraction. The effects of FGF-2 and 1-octanol were developmentally regulated, in that they were observed in the developmentally advanced lateral region of the cerebral wall but not in the medial region.

1-Octanol↗

PubMed2002

Preoperative cisplatin for initial treatment of limb osteosarcoma: its local effect and impact on prognosis.

PURPOSE: The significance of preoperative cisplatin (CDDP) as a single agent has not been assessed in terms of its effect on prognosis. The purpose of this multi-institution study was to assess the local effect of preoperative CDDP as a single agent as well as its impact on the prognosis of limb osteosarcoma. PATIENTS AND METHODS: The study group comprised 44 patients with stage IIB limb osteosarcoma who were treated with single-agent CDDP as initial preoperative chemotherapy. Two to five courses of CDDP (mean 2.4 courses) were administered intravenously and/or intraarterially as an initial preoperative treatment. The mean dose of CDDP was 3.0 mg/kg (2.5-3.4 mg/kg). The effect of the treatment was evaluated clinically and histologically. RESULTS: The clinical and histological response rates to preoperative CDDP were 56.8% and 47.6%, respectively. The survival rate was 59.1% among all patients in the study, 64.0% among those with a grade III or IV clinical response, and 52.6% among those with a grade I or II clinical response, with no significant differences between the groups. The survival rate was 70% among patients with a grade III or IV histological response, and 54.5% among those with a grade I or II histological response, with no statistical differences between the groups. CONCLUSIONS: We consider that CDDP is a useful chemotherapeutic agent for preoperative induction therapy for osteosarcoma because of the excellent local effect observed. Good responders to preoperative CDDP showed a better survival rate, but a correlation between the local response to CDDP and the survival rate was not demonstrated statistically. Systemic multidrug chemotherapy should follow preoperative CDDP to diminish the microscopic foci of metastatic disease.

Adolescent↗

PubMed2002

Simultaneous analysis of dehydroacetic acid, benzoic acid, sorbic acid and salicylic acid in cosmetic products by solid-phase extraction and high-performance liquid chromatography.

A high-performance liquid chromatographic (HPLC) method for simultaneous determination of dehydroacetic acid (DHA), benzoic acid (BA), sorbic acid (SOA) and salicylic acid (SA) was developed for application to cosmetic products. Isocratic reversed-phase HPLC was employed for quantitative analysis using tetra-n-butylammonium (TBA) hydroxide as an ion-pair reagent. Cosmetic samples were purified by solid-phase extraction using Bond-Elut SI cartridges. Four acidic preservatives were eluted with methanol from cartridges. The HPLC assay was carried out using TSK gel ODS-80TM column (5 microm, 150 x 4.6 mm I.D.). The mobile phase consisted of a mixture of water and methanol (65:35, v/v) containing 2.5 mM TBA hydroxide adjusted with phosphoric acid to pH 7.0. The calibration curves of these preservatives showed good linearity with UV detection (235 nm). The correlation coefficients were better than 0.999 in all cases. The lower limits of detection (defined as a signal-to-noise ratio of about 3) were approximately 2.5 ng for DHA, 4.0 ng for BA, 2.0 ng for SOA and 5.5 ng for SA. The procedure described here is simple, selective and is suitable for quality control of finished cosmetic products.

Benzoic Acid↗

PubMed2002

Collapse of valence transition in Yb0.8Y0.2InCu4: pressure-induced weak ferromagnetism.

We investigated the magnetization of Yb0.8Y0.2InCu4 as a function of temperature down to 0.6 K, pressure up to 1.2 GPa, and magnetic field up to 9 T. The valence transition temperature of Yb0.8Y0.2InCu4 is lowered with applying pressure. At 0.8 GPa, collapse of the valence transition and ferromagnetic ordering occur almost simultaneously. The ferromagnetic phase at 1.2 GPa is characterized by a low Curie temperature of 1.7 K and an extremely small ordered moment of 0.05 micro(B) per Yb. Some effect of screening the ordered moment may play a key role in the ferromagnetism and the valence transition.

Journal Article↗

PubMed2002

Premature apoptosis of keratinocytes and the dysregulation of keratinization in porokeratosis.

BACKGROUND: Porokeratosis is a dyskeratotic disorder of the skin characterized by cornoid lamella with parakeratosis, hyperkeratosis and loss of granular layers. The pathogenesis of porokeratosis and the mechanism(s) of its abnormal keratinization are still unknown. OBJECTIVE: To elucidate the mechanism(s) of abnormal keratinization that leads to the formation of cornoid lamellae in porokeratosis. METHODS: Apoptosis of keratinocytes was assessed in the skin of seven patients by an in situ apoptosis assay based on the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labelling (TUNEL) reaction. Patterns of loricrin and involucrin expression were examined by immunohistochemistry. RESULTS: TUNEL-positive keratinocytes were observed in the epidermis underlying the cornoid lamella in all cases examined. Furthermore, loricrin expression was interrupted there, in contrast to involucrin, which was expressed diffusely in the lesional epidermis. CONCLUSIONS: These results suggest that an abnormal early keratinocyte apoptosis accompanied by dysregulation of terminal differentiation of those cells may be involved in the pathogenesis of porokeratosis.

Adult↗

PubMed2002

Simple curettage without bone grafting for enchondromata of the hand: with special reference to replacement of the cortical window.

We studied 23 patients (25 bones) with enchondromata of the hand which were treated with simple curettage without bone grafting. The cortical window was replaced in 18 bones (group A), whereas it was not replaced in six bones (group B). In one bone, only half of the cortical window was replaced. Local recurrence was not seen in any patient. Although bone grafting was not performed, new bone formation was observed in all the patients. Radiographic and functional results were excellent in most bones. Restoration of the continuity of the cortex was seen at 3 (range, 1.5-4) months in group A and 8 (range, 6-12) months in group B. This restoration is important for the recovery of mechanical strength and we therefore consider that the cortical window should be replaced, unless this is impractical.

Adult↗

PubMed2002

In vitro activity of FK463, a novel lipopeptide antifungal agent, against a variety of clinically important molds.

The in vitro antifungal activity of FK463 against a variety of clinically important opportunistic molds was compared with amphotericin B, itraconazole and fluconazole by using the broth microdilution method M27-A specified by the National Committee for Clinical Laboratory Standards. FK463 exhibited potent activity against Aspergillus species, which was superior to those of all other compounds tested. FK463 was also active against the dematiaceous fungi Cladosporium trichoides, Exophiala spinifera, Fonsecaea pedrosoi, and Exophiala dermatitidis except for certain clinical isolates. However, FK463 had no activity against Fusarium solani, Pseudallesheria boydii, and the zygomycetes Absidia corymbifera, Cunninghamella elegans, Rhizopus oryzae, and Rhizopus microsporus var. rhizopodiformis. These results suggest that FK463 has potential utility for the treatment for infections caused by Aspergillus species and dematiaceous fungi.

Aspergillus↗

PubMed2002

FR183998, a Na+/H+ exchange inhibitor, suppresses both IL-8 content and myocardial infarct size in a cardiac ischaemia-reperfusion model in rats.

The aim of this study was to determine the effect of FR183998 (5-(2,5-dichlorothiophen-3-yl)-3-[(2-dimethylaminoethyl)carbamoyl]benzoylguanidine dihydrochloride), an Na+/H+ exchange inhibitor, on myocardial interleukin-8 (IL-8) content and myocardial infarct size in a rat ischaemia and reperfusion model. Rats underwent 30 min of ischaemia followed by 1 to 24 h of reperfusion. IL-8 content rapidly increased in reperfused rat hearts. The maximum increase in IL-8 was obtained after 3 h of reperfusion. Intravenous administration of FR183998 at 1 and 3.2 mg kg(-1), 5 min before ischaemia, significantly reduced the IL-8 level after 3 h of reperfusion (122 +/- 16 and 149 +/- 23 pg mg(-1) protein, respectively), compared with that of the saline-treated group (258 +/- 27 pg mg(-1) protein). Myeloperoxidase activity after 3 h of reperfusion was also reduced by FR183998 (from 0.83+0.19 unit g(-1) weight of tissue in the saline-treated group to 0.36 +/- 0.09 and 0.33 +/- 0.06 unit g(-1) weight of tissue in FR183998-treated groups at 1.0 and 3.2 mg kg(-1), respectively). Myocardial infarction induced by 30 min of ischaemia and 24 h of reperfusion was significantly suppressed by the same doses of FR183998 (14.0 +/- 1.5,13.5 +/- 1.9% at 1.0 and 3.2 mg kg(-1)), compared with 22.2+2.7% in the saline-treated group. These results suggestthat IL-8 may contribute to the generation of myocardial infarction in an ischaemia and reperfusion model in rats.

Animals↗

PubMed2002

[Clinical analysis of surgically resected multiple primary lung cancer].

Synchronous and metachronous lung cancer is occasionally encountered. Frequency of the occurrence is increasing because of recent progress of imaging technique such as high resolution CT and CT based annual lung survey. We analyzed clinical characteristics of both synchronous and metachronous lung cancer treated surgically in our facility. There were 20 cases of multiple lung cancer cases, which is consisted of 12 synchronous multiple lung cancer cases and 8 metachronous lung cancer cases. Mean age was 62 years old and there were 14 male and 6 female cases. Among synchronous group, 8 cases have multiple shadow in ipsilateral hemithorax and 4 cases in both side. Surgery was carried out according to the extent of the disease and lung reserve. Associated cancer was diagnosed stage IA or IB in all cases. Five-year survival was 58.9%. Meanwhile, as regards to metachronous group, mean interval between first cancer and second cancer was 73 months. Seven cases have contralateral second primary lung cancer and one case has ipsilateral second primary lung cancer. In 3 cases, histology of the first and the second disease were different and in 5 cases that were the same. The first procedures were complete resection with systemic mediastinal LN dissection. The second procedures were determined based on the lung reserve. Pathological stage of the second disease were either stage IA or IB. There were no operative mortality and 5 years survival was 75%. Since there is no operative mortality and the outcome seems satisfactory when the patient has enough lung reserve, aggressive surgical resection should be considered in the case of multiple primary lung cancer. There is an increasing chance of synchronous multiple primary lung cancer because of improvement of imaging system. We have to prepare new therapeutic strategy for those patients.

Aged↗

PubMed2002

Removal of suspended substances by coagulation and foam separation from municipal wastewater.

A new method for solid-liquid separation for wastewater incorporating simple operation and shortened treatment time is necessary for improvement of sewage systems. In this study, removal of suspended solids from municipal wastewater by coagulation and foam separation using coagulant and milk casein was examined. By adding casein before the foam separation process, the removal of suspended substances was dramatically improved. The optimum condition for treating sewage was 20 mg-Fe/L of FeCl3, 3 mg/L of casein, and pH 5.5, which resulted in a removal rates of over 98% for turbidity and SS. A removal of 96-98% was also possible for phosphate and anionic surfactant. When PAC was used, the floc was also efficiently recovered in foam by the addition of casein. It became clear that coagulation and foam separation using casein as the collector is an effective method for removing suspended solids in municipal wastewater in a short time (within 10 min).

Caseins↗

PubMed2001

Effect of FR194738, a potent inhibitor of squalene epoxidase, on cholesterol metabolism in HepG2 cells.

(E)-N-ethyl-N-(6,6-dimethyl-2-hepten-4-ynyl)-3-[2-methyl-2-(3-thienylmethoxy)propyloxy]benzylamine hydrochloride (FR194738) inhibited squalene epoxidase activity in HepG2 cell homogenates with an IC50 value of 9.8 nM. In the study using intact HepG2 cells, FR194738 inhibited cholesterol synthesis from [14C]acetate with an IC50 value of 4.9 nM, and induced intracellular [14C]squalene accumulation. On the other hand, the 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase inhibitor simvastatin reduced both cholesterol and squalene synthesis from [14C]acetate. Incubation with simvastatin for 18 h produced increases in HMG-CoA reductase activity in HepG2 cells, which was related to the degree of reduction in cholesterol synthesis. The HMG-CoA reductase activity increased by 13- and 19-fold at the concentrations of simvastatin that inhibited cholesterol synthesis by 65% and 82%, respectively. In contrast, FR194738 did not increase HMG-CoA reductase activity at the concentrations that inhibited cholesterol synthesis by 24% and 69%, and moderate increase (4.6-fold) was observed at the concentration that inhibited cholesterol synthesis by 90%. These results suggest that non-sterol metabolite(s) derived from mevalonate prior to the squalene epoxidation step in the cholesterol synthetic cascade have a regulatory role in the suppression of HMG-CoA reductase activity. We speculate that FR194738 inhibits cholesterol synthesis with a minimal change of the regulator(s) and would be highly effective in the treatment of hypercholesterolemia.

Benzylamines↗

PubMed2001

Hepatotoxin rubratoxin B induced the secretion of TNF-alpha, IL-8, and MCP-1 in HL60 cells.

Induction of cytokine secretion by rubratoxin B was investigated using HL60 cells. Tumor necrosis factor (TNF)-alpha and interleukin (IL)-8 were secreted from 40 and 80 microg/ml rubratoxin B-treated cells. In 20 and 40 microg/ml rubratoxin B-treated samples, monocyte chemotactic protein (MCP)-1 was released. These rubratoxin B-induced cytokines are known to promote liver myelocytic cell infiltration, and activate cytokine-recruited cells. As a result, recruited myelocytic cells are considered to contribute to hepatic injury. We investigated the effects of tyrosine kinase inhibitors genistein and emodin. Genistein reduced the release of all three cytokines from rubratoxin B-treated cells. Likewise, emodin diminished the secretion of MCP-1. Alternatively, emodin reversed on the secretion of TNF-alpha, and the release of IL-8 was not affected. Since emodin did not impede rubratoxin B-caused TNF-alpha and IL-8 secretion, they appeared to be regulated differently from MCP-1 secretion, suggesting that rubratoxin B exerts its toxicity using two or more signal transduction pathways.

Chemokine CCL2↗

PubMed2001

FR226807: a potent and selective phosphodiesterase type 5 inhibitor.

We describe the pharmacological characteristics of a novel phosphodiesterase type 5 inhibitor FR226807, N-(3,4-dimethoxybenzyl)-2-[[(1R)-2-hydroxy-1-methylethyl]amino]-5-nitrobenzamide. FR226807 inhibited phosphodiesterase type 5 isolated from human platelets with an IC(50) value of 1.1 nM. FR226807 also inhibited phosphodiesterase type 6 with an IC(50) of 20 nM; however, the IC(50) value for phosphodiesterase type 6 was 18-fold higher than that for phosphodiesterase type 5. The IC(50) values of FR226807 for other phosphodiesterases (phosphodiesterase type 1, phosphodiesterase type 2, phosphodiesterase type 3, and phosphodiesterase type 4) were 1000-fold higher than that for phosphodiesterase type 5. FR226807 increased the cyclic guanosine monophosphate (cGMP) content in corpus cavernosum isolated from rabbit, an effect associated with relaxation of the muscle. FR226807 enhanced the relaxation response induced by electrical field stimulation of corpus cavernosum isolated from the rabbit. In an anesthetized dog model for the evaluation of erectile function, intravenous administration of FR226807 prolonged the time to return to 75% of maximal intracavernosal pressure after cessation of electrical stimulation of the pelvic nerve. In summary, FR226807 is a potent and highly selective phosphodiesterase type 5 inhibitor with an augmentative effect on penile erection and will be useful for the treatment of erectile dysfunction.

3',5'-Cyclic-GMP Phosphodiesterases↗

PubMed2001

The spinal antinociceptive effect of FR140423 in mice involvement of the descending noradrenergic and serotonergic systems.

In this study, we investigated the role of descending monoaminergic systems in the antinociceptive activity of FR140423, 3-(difluoromethyl)-1-(4-methoxyphenyl)-5-[4-(methyl sulfinyl)phenyl]pyrazole, by using the tail-pinch test in mice and various monoamine depletors. The antinociceptive effects of FR140423 given p.o. and i.t. with ED50 values of 22 mg/kg and 3.5 microg/mouse, respectively, in the tail-pinch test were antagonized by reserpine, 6-hydroxydopamine plus nomifensine, and p-chlorophenylalanine treatment, whereas the antinociceptive action of morphine in this assay was attenuated by reserpine and 6-hydroxydopamine plus nomifensine but not by p-chlorophenylalanine treatment. These results suggest that both descending noradrenergic and serotonergic systems are involved in the antinociceptive activity of spinally and systemically administered FR140423 against mechanical noxious stimuli. The mechanisms underlying the suppressive action of FR140423 on the nociceptive response may differ from those of morphine in mice.

Analgesics↗

PubMed2001

The stress kinase mitogen-activated protein kinase kinase (MKK)7 is a negative regulator of antigen receptor and growth factor receptor-induced proliferation in hematopoietic cells.

The dual specificity kinases mitogen-activated protein kinase (MAPK) kinase (MKK)7 and MKK4 are the only molecules known to directly activate the stress kinases stress-activated protein kinases (SAPKs)/c-Jun N-terminal kinases (JNKs) in response to environmental or mitogenic stimuli. To examine the physiological role of MKK7 in hematopoietic cells, we used a gene targeting strategy to mutate MKK7 in murine T and B cells and non-lymphoid mast cells. Loss of MKK7 in thymocytes and mature B cells results in hyperproliferation in response to growth factor and antigen receptor stimulation and increased thymic cellularity. Mutation of mkk7 in mast cells resulted in hyperproliferation in response to the cytokines interleukin (IL)-3 and stem cell factor (SCF). SAPK/JNK activation was completely abolished in the absence of MKK7, even though expression of MKK4 was strongly upregulated in mkk7(-/-) mast cell lines, and phosphorylation of MKK4 occurred normally in response to multiple stress stimuli. Loss of MKK7 did not affect activation of extracellular signal-regulated kinase (ERK)1/2 or p38 MAPK. mkk7(-/-) mast cells display reduced expression of JunB and the cell cycle inhibitor p16INK4a and upregulation of cyclinD1. Reexpression of p16INK4a in mkk7(-/-) mast cells abrogates the hyperproliferative response. Apoptotic responses to a variety of stimuli were not affected. Thus, MKK7 is an essential and specific regulator of stress-induced SAPK/JNK activation in mast cells and MKK7 negatively regulates growth factor and antigen receptor-driven proliferation in hematopoietic cells. These results indicate that the MKK7-regulated stress signaling pathway can function as negative regulator of cell growth in multiple hematopoietic lineages.

Animals↗

PubMed2001

Intratumoral delivery of interleukin 12 expression plasmids with in vivo electroporation is effective for colon and renal cancer.

We report on an antitumor treatment involving electrogene therapy (EGT), a newly developed in vivo gene transfer method using electroporation. We carried out in vivo EGT in a subcutaneous model of CT26 colon carcinoma cells, using plasmid DNAs encoding interleukin 12 (IL-12) subunits. For this purpose, we developed two IL-12 expression systems: a cotransfer system using a plasmid encoding the IL-12 p40 subunit and a plasmid encoding the IL-12 p35 subunit, and a single-vector system using a plasmid expressing a p40-p35 fusion protein. Both transfer systems significantly inhibited the growth of CT26 tumor. Immunohistochemical analysis of IL-12 EGT-treated tumors revealed enhanced infiltration of CD8(+) cells into the tumor tissue, while reverse transcriptase-polymerase chain reaction confirmed the increased expression of interferon gamma within treated tumors. The same IL-12 EGT applied to the nude mouse model was not effective, suggesting the critical role of T cell infiltration in this treatment. The inhibitory effects revealed in experiments in which previously treated mice were rechallenged with a second inoculation of CT26 tumor cells suggested that IL-12 EGT may also establish partial systemic antitumor immunity. The growth of IL-12 EGT-treated Renca tumors, a renal cell carcinoma, was also significantly inhibited. These findings suggest that EGT of the IL-12 gene has the potential to be an effective anticancer gene therapy.

Animals↗