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Biomedical subjects

T Seto

Publications and source records attributed to T Seto.

At least 19 recordsLinked to original sources
PubMed2006

Intrapleural hypotonic cisplatin treatment for malignant pleural effusion in 80 patients with non-small-cell lung cancer: a multi-institutional phase II trial.

To assess the effect and toxicity of hypotonic cisplatin treatment (HPT) consisting of the intrapleural administration of cisplatin in distilled water for malignant pleural effusion in patients with non-small-cell lung cancer (NSCLC). Non-small-cell lung cancer patients with cytologically proven and previously untreated malignant pleural effusion were enrolled into this study. Firstly, the lung was fully re-expanded by a tube thoracostomy, and then 25 mg cisplatin in 500 ml of distilled water was instilled through a chest tube and then the tube was clamped. After 1 h, the tube was declamped and allowed to drain. The chest tube was removed when the pleural effusion volume decreased to 200 ml or less per day. A complete response (CR) was considered to occur when the pleural effusion disappeared. A partial response (PR) was determined to occur when the volume of pleural effusion remained under (1/4) of hemithorax. The response at 4 weeks was evaluated by an extramural review. Out of 84 patients enrolled from February 1998 to August 2002, 80 patients were eligible and analysed in the present study. The toxicity of HPT was acceptable. Neither a haematological toxicity of any grade nor grade 4 nonhaematological toxicity was observed. Grade 3 nonhaematological toxicities were observed, including nausea (4%), vomiting (3%), pyothorax (1%) and dyspnoea (1%). The median time of drainage from HTP was 4 days. Twenty-seven (34%) and 39 (49%) patients achieved CR and PR, respectively, for an overall response rate of 83% (95% confidence interval, 74-91%). The median duration of the response was 206 days. The median survival time of all patients was 239 days. Hypotonic cisplatin treatment for malignant pleural effusion of NSCLC is therefore considered to be feasible and effective. A phase III study of HPT is thus warranted.

Adult↗
PubMed2006

The effects of a neutrophil elastase inhibitor on the postoperative respiratory failure of acute aortic dissection.

BACKGROUND: Postoperative respiratory failure is often encountered in patients suffering from acute aortic dissection (AAD) and is believed to be influenced by release of neutrophil elastase after cardiopulmonary bypass. Sivelestat is a specific neutrophil elastase inhibitor, and this study aims to evaluate the effects of sivelestat on postoperative respiratory failure due to AAD. METHODS AND RESULTS: Patients who were operated for AAD from January 2000 to April 2005 and who had less than 300 mmHg initial postoperative PaO (2)/FiO (2) were investigated retrospectively and divided into two groups. Group 1 (n = 9) received intravenous administration of sivelestat immediately after the operation, while Group II (n = 9) received no sivelestat. There were no significant differences between Group I and II with respect to patients' characteristics or background (age, body weight, operating time, cardiopulmonary bypass time, amount of bleeding, preoperative WBC number and initial PaO (2)/FiO (2)). Though patients in Group I showed a subtle improvement in certain parameters such as PaO (2)/FiO (2), A-aDO (2) and respiratory index (RI) over a 3-day observation period compared to those of Group II, there were no significant differences. Neither postoperative mechanical ventilation time nor ICU stay differed between Group I and II. However, Group I showed a significantly greater improvement in the ratio of RI to initial RI on the 3POD compared to that of Group II (61.6 +/- 44.2 % vs. 111.9 +/- 40.9 %, P = 0.02). CONCLUSION: Inhibiting the activity of the neutrophil elastase may attenuate the postoperative respiratory complications of patients with AAD.

Acute Disease↗
PubMed2005

UFT plus gemcitabine combination chemotherapy in patients with advanced non-small-cell lung cancer: a multi-institutional phase II trial.

A multi-institutional phase II trial was conducted to evaluate the efficacy and toxicity of combination chemotherapy consisting of gemcitabine and UFT, which is composed of tegafur and uracil, for non-small-cell lung cancer (NSCLC) patients. Patients with advanced NSCLC received an oral administration of UFT (tegafur 200 mg m(-2)) b.i.d. from days 1 to 14 and intravenous injection of gemcitabine 900 mg m(-2) on days 8 and 15. This treatment was repeated every 4 weeks. A total of 44 patients were enrolled into this trial. The median age of all patients was 74 years, with 23 patients younger than 75 years and 21 patients with 75 years of age or older. A total of 18 patients (41%) achieved a partial response. The median survival time was 13.2 months and the 1-year survival rate was 59%. The most common grade 3-4 toxicity was neutropenia (57%). The frequency of grade 3 nonhaematologic toxicities was less than 5%. In addition, no significant difference in the response, survival or toxicities was observed between the patients younger than and those older than 75 years of age. This combination chemotherapy demonstrated a promising effectiveness and acceptable toxicity in patients with advanced NSCLC, even in patients older than 75 years. .

Aged↗
PubMed2002

A phase I study of combination chemotherapy with gemcitabine and oral UFT for advanced non-small cell lung cancer.

A phase I study was carried out to determine the optimal dose and administration schedule for combined UFT plus gemcitabine therapy in patients with non-small cell lung cancer. Twenty-four patients (including 11 patients previously treated with cisplatin as the key drug) received oral UFT 400 mg x m(-2) on days 1 to 14 with intravenous infusions of gemcitabine (800 mg x m(-2) on days 8 and 15, or 900 mg x m(-2) on days 8 and 15, or 900 mg x m(-2) on days 1, 8 and 15). The most appropriate dosing option appeared to be 400 mg x m(-2) per day of oral UFT for 14 consecutive days with 900 mg x m(-2) gemcitabine on days 8 and 15. Eight of the 24 patients achieved partial response. The combination chemotherapy UFT and gemcitabine was well tolerated and may benefit patients with advanced non-small cell lung cancer. A multicentre phase II study using a 3-weekly regimen is in progress.

Administration, Oral↗
PubMed2001

XAFS studies of Tb or Eu cored dendrimer complexes with various properties of luminescence.

We studied the extended X-ray absorption fine structure (EXAFS) of Tb or Eu L3-edge of Tb(III) or Eu(III)-cored complexes of different luminescence to which different poly(benzyl ether) dendrons coordinated. The complexes were prepared via a ligand exchange reaction of dendritic carboxylic acid and acetate. Results show that (a) the Eu complex of the first generation of the 3,4- or 3,5-dibenzyloxyphenyl type had a coordination structure different from that of the 2,4-dibenzyloxyphenyl type; (b) the Eu complex of the first generation of 3,5-dinaphthylmethoxyphenyl type had a Eu-O coordination number higher than the total number of oxygen atoms in the carboxylate groups; (c) the Tb complex of the bulky fourth generation had a Th-O coordination number higher than that of the first generation. These results show that the different poly(benzyl ether) dendrons cause the different coordination, which might differently influence the luminescence properties of the complexes.

Biological Assay↗
PubMed2001

Cerebroprotective action of a Na+/Ca2+ channel blocker NS-7. II. Effect on the cerebral infarction, behavioral and cognitive impairments at the chronic stage of permanent middle cerebral artery occlusion in rats.

We have previously shown that NS-7 [4-(4-fluorophenyl)-2-methyl-6-(5-piperidinopentyloxy)pyrimidine hydrochloride] reduces the size of cerebral infarction measured by 2,3,5-triphenyltetrazolium chloride staining at 48 h after permanent middle cerebral artery occlusion (MCAO) in rats. To determine whether NS-7 improves the pathological and behavioral changes at the chronic stage of MCAO, the effect of this compound on the cerebral infarction as well as the neurological and cognitive impairments was investigated 7 days after MCAO. Single or five daily injections of NS-7 (0.125-0.5 mg/kg, i.v.) significantly reduced the infarct volume and improved the neuronal dysfunction including the hind leg paralysis, walking disability and motor incoordination, and the deficit of passive avoidance task, although the neuroprotective efficacy was not different among these dosing regimens. On the other hand, the effects of single versus repeated injections of NS-7 at 0.1 or 0.2 mg/kg on the neurological symptoms were compared at 4 weeks after MCAO. At a lower dose, repeated but not single injection of NS-7 significantly improved the neurological symptoms, although the single injection was effective at a higher dose. From these findings, it is suggested that NS-7 reverses the behavioral and cognitive dysfunction observed at the chronic stage of cerebral ischemia by suppressing the cerebral infarction.

Animals↗
PubMed2001

Brain magnetic resonance imaging in 23 patients with mucopolysaccharidoses and the effect of bone marrow transplantation.

A longitudinal study of cranial magnetic resonance imaging (MRI) was carried out in 23 patients with mucopolysaccharidoses (MPS); 1 each of types IH, VI, and VII; 2 of type IS; 10 of type II; and 4 each of types IIIB and IVA. Six types of distinct abnormalities were 1) cribriform changes or spotty changes in the corpus callosum, basal ganglia, and white matter; 2) high-intensity signal in the white matter on T2-weighted image; 3) ventriculomegaly; 4) diffuse cerebral cortical atrophy; 5) spinal cord compression; and 6) megacisterna magna. The cribriform changes that corresponded to dilated perivascular spaces were found in the patients with MPS IS, II, and VI. The patchy and diffuse intensity changes were found in the patient with MPS II and IIIB, respectively. MPS IH and the severe type of MPS II showed marked ventriculomegaly. Marked cerebral atrophy was observed in all MPS IIIB patients and in the severe type of MPS II patients. Spinal cord compression was a feature usually observed in MPS IH, IVA, VI, and VII. Megacisterna magna was frequent in the patients with MPS II (6/10). In two of five patients, the therapeutic effect of bone marrow transplantation (BMT) was remarkable. Both the cribriform changes and the intensity change of the white matter in a MPS VI patient disappeared eight years after the BMT. Slight improvement of cribriform change was noted in one patient with MPS II three years after the BMT. MRS was not sufficient to estimate the accumulation of glycosaminoglycans but was useful for evaluating neuronal damages.

Adolescent↗
PubMed2001

Hemadsorption expressed by cloned H genes from subacute sclerosing panencephalitis (SSPE) viruses and their possible progenitor measles viruses isolated in Osaka, Japan.

Most subacute sclerosing panencephalitis (SSPE) viruses, including our Osaka-1, -2, and -3 strains isolated in Osaka, have shown negative hemadsorption (HAD) by African green monkey red blood cells. This property has been thought to be characteristic of SSPE virus as compared to the positive reaction of the standard Edmonston strain of measles virus (MV). However, this assumption has become quite obscure because MV mutates frequently at the genetic level during its multiplication and also because recent field strains isolated by lymphoblastoid cell lines have shown negative HAD. To investigate the above issue, the nucleotide sequences of the hemagglutinin (H) genes from SSPE virus Osaka-1, -2, or -3 strains were compared to those of various MV field strains isolated in Osaka by Vero cells. The H gene sequences of three SSPE strains were relatively conserved without such biased hypermutation as had been observed in the matrix (M) gene of three SSPE strains. However, this analysis of the H gene sequence of the SSPE viruses enabled us to deduce possible progenitor MVs, which are in agreement with the deduction from the M gene analysis we reported previously. The HAD of Vero cells transfected with the cloned H cDNAs from the SSPE strains and their progenitors suggested that negative HAD of the SSPE viruses has been maintained as one of original properties of the progenitor MVs rather than having been acquired as an altered one during long-term persistent infection in the brains of patients with SSPE.

Amino Acid Sequence↗
PubMed2001

Noise-enhanced heart rate and sympathetic nerve responses to oscillatory lower body negative pressure in humans.

By injecting noise into the carotid sinus baroreceptors, we previously showed that heart rate (HR) responses to weak oscillatory tilt were enhanced via a mechanism known as "stochastic resonance." It remains unclear, however, whether the same responses would be observed when using oscillatory lower body negative pressure (LBNP), which would unload the cardiopulmonary baroreceptors with physically negligible effects on the arterial system. Also, the vasomotor sympathetic activity directly controlling peripheral resistance against hypotensive stimuli was not observed. We therefore investigated the effects of weak (0 to approximately -10 mmHg) oscillatory (0.03 Hz) LBNP on HR and muscle sympathetic nerve activity (MSNA) while adding incremental noise to the carotid sinus baroreceptors via a pneumatic neck chamber. The signal-to-noise ratio of HR, cardiac interbeat interval, and total MSNA were all significantly improved by increasing noise intensity, while there was no significant change in the arterial blood pressure in synchronized with the oscillatory LBNP. We conclude that the stochastic resonance, affecting both HR and MSNA, results from the interaction of noise with the signal in the brain stem, where the neuronal inputs from the arterial and cardiopulmonary baroreceptors first come together in the nucleus tractus solitarius. Also, these results indicate that the noise could induce functional improvement in human blood pressure regulatory system in overcoming given hypotensive stimuli.

Adult↗
PubMed2001

Morphological control of laser-synthesized silicon nanoparticles.

Size and crystallinity controlled silicon nanoparticles were prepared by a laser ablation, in situ annealing and mobility size-selection with a differential mobility analyzer (DMA). The shape and crystal structure of generated particles were observed by a transmission electron microscopy (TEM). Both densification of agglomerates and crystal growth of the particles were observed. The size of silicon primary particle was increased by the annealing, and the uniformity of the particle classified at 10 nm was improved as a result.

Crystallization↗
PubMed2001

[The effects of kampo-formulation and the constituting crude drugs, prescribed for the treatment of peptic ulcer on H,K-ATPase activity].

We studied the effects of 17 kinds of Kampo-formulations prescribed for the treatment of peptic ulcer on H,K-ATPase activity. The activity was strongly inhibited by San-o-shashin-to ([symbol: see text], IC50 = 82 micrograms/ml), Bukuryo-in ([symbol: see text], IC50 = 110 micrograms/ml), Shakuyaku-kanzo-to ([symbol: see text], IC50 = 170 micrograms/ml), Hange-koboku-to ([symbol: see text], IC50 = 290 micrograms/ml), Dai-saiko-to ([symbol: see text], IC50 = 340 micrograms/ml), Irei-san ([symbol: see text], IC50 = 380 micrograms/ml) than other Kampo-formulations. Among the 17 kinds of crude drugs contained in these Kampo-formulation, Rhei Rhizoma, Coptidis Rhizoma, Glycyrrhiza Radix, Cinnamomi Cortex, and Poria have notable inhibitory effects (IC50 = 19-57 micrograms/ml). H,K-ATPase activity was inhibited by sennoside A (Rhei Rhizoma), sennoside B (Rhei Rhizoma), ergosterol (Poria), coptisine (Coptidis Rhizoma), glycyrrhizin (Glycyrrhiza Radix), glycyrrhetic acid (Glycyrrhiza Radix), gallic acid (Cinnamomi Cortex) in the 21 components of these crude drugs (IC50 = 1.6-7.9 x 10(-4) M). The inhibition of San-o-shashin-to and Bukuryo-in is considered to be mainly attributed to Rhei Rhizoma and Poria, respectively. The anti-gastric ulcer effects of San-o-shashin-to and Bukuryo-in may be ascribed to the inhibition of H,K-ATPase activity.

Anti-Ulcer Agents↗
PubMed2001

Effective plasma concentration of a novel Na+/Ca2+ channel blocker NS-7 for its cerebroprotective actions in rats with a transient middle cerebral artery occlusion.

The effect of a novel Na+/Ca2+ channel blocker NS-7 [4-(4-fluorophenyl)-2-methyl-6-(5-piperidinopentyloxy) pyrimidine hydrochloride] on the cerebral infarction, edema, and mortality was examined in rats with a transient middle cerebral artery occlusion (MCAO), and the effective plasma concentration of this compound for producing the cerebroprotective action was subsequently determined. MCA was occluded by inserting a thread through internal carotid artery for 2 h, and then recirculated for 6 h. NS-7 (0.125-1 mg/kg), when injected i.v. immediately after recirculation, significantly reduced the infarct volume as well as the cerebral edema. Delayed treatment with NS-7 at 1 h after recirculation produced an equivalent inhibition of the infarction, and was still effective, although to a lesser extent, when injected at 2 h but not 3 h after recirculation. Glycerol (4 g/kg) suppressed the cerebral edema but did not reduce the size of cerebral infarction in the cerebral cortex or striatum. Therefore, it is likely that the suppression of brain edema does not always lead to the reduction of the infarct size. NS-7 treated in combination with glycerol further decreased the water content in the occluded brain. Moreover, NS-7 significantly lowered the mortality observed up to 10 days after a transient MCAO. From these data, it is suggested that the presence of NS-7 in plasma during 1 to 3 h after recirculation is important for producing the neuroprotective action. To determine the pharmacologically effective plasma concentration of NS-7, the effect of continuous infusion of this compound on the cerebral infarction was examined. Infusion of NS-7 at 0.3 mg/kg over 2 h, starting immediately after recirculation, significantly reduced the infarct size. Its plasma concentration during 1 to 3 h was 14.5 to 28.5 ng/ml (36.9-72.3 nM). From these finding it is suggested that NS-7 has a potent anti-infarct action in addition to antiedema action in the rat transient MCAO model. Moreover, its effective plasma concentration was assumed to be 36.9 to 72.3 nM.

Animals↗
PubMed2001

[A case of recurrent breast cancer successfully treated with docetaxel].

A 50-year-old female underwent mastectomy for left breast cancer in June, 1991. She received tamoxifen for 36 months and tegafur for 30 months as adjuvant therapy. In November 1997, liver, lung and para-aortic lymph node recurrences were found, and we treated her six times with docetaxel 60 mg. After the chemotherapy, a complete response (CR) of all metastatic lesions was achieved and her serum CA15-3 level was decreased. Adverse reactions were grade 4 neutropenia, grade 2 alopecia, fever, and grade 1 edema. She received medroxyprogesterone acetate after the chemotherapy and has been well without re-growth of any metastases for over eight months.

Antineoplastic Agents, Phytogenic↗
PubMed2000

Effects of normal alcohols and isoflurane on lipid headgroup dynamics in nicotinic acetylcholine receptor-rich lipid vesicles.

The trend of evidence suggests that general anesthetics act directly on proteins in the neural membrane. However, the fact that the functions of nicotinic acetylcholine receptor (sodium permeability, desensitization rate) are modulated by the composition of the membrane in which it is reconstituted has been thought to be a result of the variation of interactions between acetylcholine receptor and membrane. In this study, protein-lipid interaction at the level of the lipid headgroup was investigated using electron paramagnetic resonance (EPR) and headgroup spin label. Lipid headgroup mobility was evaluated with rotational correlation time from the EPR spectrum. Protein-lipid interaction at headgroup depth was demonstrated from the motionally restricted component of the spectrum. Rotational correlation time increased to 13 ns from 7 ns due to protein-lipid interaction. The effect of anesthetic (ethanol, 1-hexanol, and isoflurane) on protein-lipid interaction was investigated, and the correlation time was 13 ns. It is concluded that the anesthetics used in this study did not alter protein-lipid interaction at the level of the lipid headgroup, so far as observed by rotational correlation time, without excluding the possibility that anesthetics that perturb protein-lipid interactions modulate receptor functions via this mechanism.

Alcohols↗
PubMed2000

NMR study of volatile anesthetic binding to nicotinic acetylcholine receptors.

New lines of evidence suggest that volatile anesthetics interact specifically with proteins. Direct binding analysis, however, has been largely limited to soluble proteins. In this study, specific interaction was investigated between isoflurane, a clinically important volatile anesthetic, and membrane-bound nicotinic acetylcholine receptors (nAChRs) from Torpedo electroplax, using (19)F nuclear magnetic resonance spectroscopy and gas chromatography. The receptors were reconstituted into 1, 2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) lipid vesicles. After correcting for nonspecific partitioning into the lipid, the equilibrium dissociation constant, K(d), of isoflurane binding to nAChR at 15 degrees C was found to be 0.36 +/- 0.03 mM. This value is within the clinically relevant concentration range of the agent. Based on the receptor concentrations in the vesicle suspension assayed by the bicinchoninic acid method and the fraction of bound isoflurane, X(b), determined by gas chromatography, an estimate of an average of 9-10 specifically bound isoflurane molecules can be made for each receptor, or two for each subunit. Upon binding, the transverse relaxation time constant (T(2)) of (19)F resonance of isoflurane is decreased by nearly three orders of magnitude, indicating a dramatic reduction in the mobility of specifically bound isoflurane. Kinetic analysis reveals that the off rate of binding, k(-1), is 1.7 x 10(4) s(-1). The on rate, k(+1), can thus be calculated to be approximately 4.8 x 10(7) M(-1) s(-1), suggesting a nearly diffusion-limited association. This is in contrast to anesthetic binding to a soluble protein, bovine serum albumin (BSA), where k(+1) and k(-1) are at least an order of magnitude slower. It is concluded that the presence of lipids may be critical for the correct evaluation of binding kinetics between volatile anesthetics and neuronal receptors.

Anesthetics, Inhalation↗
PubMed2000

Cell surface expression of immature H glycoprotein in measles virus-infected cells.

Two forms of hemagglutinin (H) protein, one with an apparent molecular mass of 78 kDa (78K H protein) and the other with that of 74 kDa (74K H protein), are present in cells infected with measles virus (MV). We previously observed that only the mature 78K H protein, a completely glycosylated form of the 74K H protein, was expressed on the cell surface of the infected cells. In the present study, we detected transient expression of the 74K H protein on the cell surface of infected cells by pulse-chase studies, although the level of this expression was much lower than that of the 78K H protein. On the cell surface the 74K H protein was present as dimers and sensitive to endo-beta-N-acetylglucosaminidase H digestion. Treatment with brefeldin A, which blocks the transport of membrane and secretory proteins from the endoplasmic reticulum to the Golgi apparatus, inhibited the cell surface expression of the 78K H protein, but not that of the 74K H protein. These data suggest that a part of the MV 74K H proteins could be transported directly to the cell surface - probably via an alternative pathway - without processing to the complex form in the Golgi apparatus.

Animals↗
PubMed2000

Detection of bone marrow metastases of small cell lung cancer with magnetic resonance imaging: early diagnosis before destruction of osseous structure and implications for staging.

Small cell lung cancer (SCLC) frequently metastasizes to bone and bone marrow. Skeletal scintigraphy and bone marrow cytology or biopsy, are incorporated into the staging procedures to examine these organs. However, skeletal scintigraphy is not highly specific to metastases, and only one or two bone marrow sites can be examined by cytology or biopsy. We have already reported that magnetic resonance imaging (MRI) could improve the sensitivity in detecting bone marrow metastases. The result of the bone marrow MRI was an independent prognostic factor of SCLC patients [9]. In the present study, we analyzed the results of skeletal scintigraphy and bone marrow aspiration with special reference to the results of MRI examination. We also analyzed the relationship between bone marrow lesions and bone lesions. For this purpose, we visualized bone marrow metastases with MRI and determined their anatomical locations and sizes. Approximately half of bone marrow lesions stayed in bone marrow during follow-up period ranging from 57 to 154 days, whereas about half of them were accompanied by hot spots in follow-up skeletal scintigraphy, which indicates the destruction of osseous structure. Additionally, 87.5% of osteolytic changes that newly appeared in skeletal scintigraphy were preceded by adjacent bone marrow lesions. All new lesions that appeared in follow-up skeletal scintigraphy within 3 months after the initial presentation had the preceding bone marrow lesions. These results mean that almost all lesions in skeletal scintigraphy derived from bone marrow metastases. Furthermore, appreciable volume of cancer cells is present in bone marrow before osteolytic changes appear in skeletal scintigraphy.

Adult↗