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T Kinoshita

Publications and source records attributed to T Kinoshita.

At least 91 records · Page 5Linked to original sources
PubMed2001

Phase II study of sequential high-dose methotrexate and fluorouracil combined with doxorubicin as a neoadjuvant chemotherapy for scirrhous gastric cancer.

BACKGROUND: The prognosis of scirrhous gastric cancer remains poor when it is treated with surgical resection alone or chemotherapy alone. A phase II study of sequential high-dose methotrexate and fluorouracil, combined with doxorubicin, as a neoadjuvant chemotherapy was conducted in an attempt to evaluate the efficacy of this regimen in improving the survival of patients with scirrhous gastric cancer. METHODS: Patients were eligible if they had potentially resectable scirrhous gastric cancer with adequate organ functions and no prior treatment. The treatment schedule consisted of methotrexate (1 g/m2, day 1) fluorouracil (1.5 g/m2, day 1), leucovorin (15 mg/m2, days 2-4), and doxorubicin (30 mg/m2, day 15), repeated at a 28-day interval, and followed by radical surgery. RESULTS: A total of 20 eligible patients were registered. Objective responses in the neoadjuvant chemotherapy segment were observed in 3 of the 20 (15%) patients. No complete remission was observed. The neoadjuvant chemotherapy was associated with grade 3 or 4 neutropenia in 14 of the 20 (70%) patients. The median time from the initial therapy to the operative day was 82 days. Thirteen of the 20 (65%) patients underwent curative resection. No treatment-related deaths occurred. However, the 2-year survival rate in this treatment program (25%) did not show any superiority over that in historical controls. CONCLUSIONS: Sequential high-dose methotrexate and fluorouracil, combined, with doxorubicin, as a neoadjuvant chemotherapy for scirrhous gastric cancer did not improve the survival rate in spite of improving the curative resection rate.

Adenocarcinoma, Scirrhous↗
PubMed2001

Spatial assessment by magnetic resonance cholangiopancreatography for preoperative imaging in partial pancreatic head resection.

BACKGROUND: Partial pancreatic head resection has been recommended for intraductal papillary mucinous tumor (IPMT). We report the usefulness of preoperative assessment by magnetic resonance cholangiopancreatography (MRCP) compared with endoscopic retrograde cholangiopancreatography (ERCP). METHODS: We studied 12 cases of surgically resected IPMT in the pancreatic head. The MRCP and ERCP images were interpreted, and we examined the detection rate of each imaging technique for the Wirsung duct, the Santorini duct, the entire cystic tumor, and the communication between the tumor and the ducts. RESULTS: In all cases MRCP correctly identified the entire cystic tumor, and the communication between the tumor and the pancreatic ducts was seen in 64% of cases. In contrast, the detection rate by ERCP of the entire cystic tumor and of the communication between the cystic tumor and the ducts was only 8% and 18%, respectively. CONCLUSION: MRCP clearly showed the relationship of the cystic tumor and the pancreatic ducts and was very useful for preoperative imaging for partial pancreatic head resection.

Aged↗
PubMed2001

Source localization of EEG activity during hypnotically induced anxiety and relaxation.

The engagement of different brain regions which implement subjectively experienced emotional states in normals is not completely clarified. Emotional states can conveniently be induced by hypnosis-based suggestions. We studied brain electric activity during hypnotically induced anxiety and relaxation in 11 right-handed normals (5 males, 6 females, mean age 26.5+/-7.6 years). After induction of light hypnosis, anxiety and then relaxation was suggested using a standardized text (reverse sequence in half of the subjects). Nineteen-channel, eyes-closed EEG (20 artifact-free s/subject) was analyzed (source localization using FFT approximation and low resolution electromagnetic tomography, LORETA). Global tests revealed the strongest difference (P<0.005) between EEG source gravity center locations during the two emotional states in the excitatory beta-2 EEG frequency band (18.5-21 Hz). Post hoc tests showed that the sources were located more right during anxiety than during relaxation (P=0.01). LORETA specified that anxiety showed maximally stronger activity than relaxation in right Brodmann area 10, and relaxation showed maximally stronger activity than anxiety in left Brodmann area 22. Clearly, the two induced emotional states were associated with activity of different neural populations. Our results agree with reports on brain activity shifted to the right (especially fronto-temporal) during negative compared with positive emotions, and support the role of beta-2 EEG frequency in emotional states.

Adult↗
PubMed2001

Postural sway and diabetic peripheral neuropathy.

The focus of this paper is to evaluate the relationship between postural sway assessed by a gravicorder and peripheral neuropathy in patients with type 2 diabetes. Posturography (GRAVICHART), electrophysiological tests, and power spectrum analysis of heart rate fluctuations were performed in the following age-matched subjects: 123 type 2 diabetic patients without peripheral neuropathy, 32 type 2 diabetic patients with peripheral neuropathy, and 55 healthy control subjects. All diabetic patients with a history of clinical neurological dysfunction were excluded from the study. Significant correlations were found between parameters of GRAVICHART and some parameters of the electrophysiological tests as well as the parameters of heart rate variability. The envelope area and the length per time were larger in type 2 diabetic patients with peripheral neuropathy than in patients without peripheral neuropathy and the control subjects. There were no significant differences in the GRAVICHART parameters between diabetic patients without neuropathy and the healthy control subjects. Type 2 diabetic patients with peripheral neuropathy exhibited an inability to maintain an upright posture. The GRAVICHART can indicate the early stage of postural balance impairment.

Albuminuria↗
PubMed2001

Oncostatin M suppresses generation of lymphoid progenitors in fetal liver by inhibiting the hepatic microenvironment.

OBJECTIVE: Interaction between hematopoietic cells and stromal cells is important for regulation of hematopoiesis. Numerous soluble and membrane-bound factors directly regulating hematopoiesis have been documented, but little is known about how stromal cell activity is controlled. We previously reported that fetal hepatic cells in primary culture create the hematopoietic microenvironment and support expansion of blood cells from hematopoietic stem cells. In this study, we focused on lymphopoiesis reconstituted in our culture system and analyzed how stroma-mediated lymphopoiesis is regulated during embryonic development. MATERIALS AND METHODS: Subconfluent cultures of murine fetal hepatic cells were cocultured with hematopoietic stem cells derived from fetal liver in the presence of various cytokines. After 10 days of incubation, hematopoietic cells floating over the stromal layer were analyzed by various assays, including cell proliferation and FACS analysis. RESULTS: We found that oncostatin M, an inducer of hepatic development, strongly inhibited generation of B220(+) lymphocytic cells and colony-forming unit-interleukin-7 (CFU-IL-7) from hematopoietic stem cells in our coculture system. In contrast, oncostatin M did not directly inhibit proliferation of B cells in response to IL-7 and SCF in semisolid cultures. Analysis of antigen expression in lymphoid cells revealed that oncostatin M apparently did not arrest cells at a particular stage of B-cell development. CONCLUSIONS: The results suggest that oncostatin M inhibits lymphopoiesis by suppressing stromal activity of fetal hepatic cells to stimulate generation of CFU-IL-7 from their progenitors rather than by acting directly on lymphocytic cells.

Animals↗
PubMed2001

Murine homologs of deltex define a novel gene family involved in vertebrate Notch signaling and neurogenesis.

Notch signaling plays an important role in cell-fate specification in multicellular organisms by regulating cell-cell communication. The Drosophila deltex gene encodes a modulator of the Notch pathway that has been shown to interact physically with the Ankyrin repeats of Notch. We isolated four distinct cDNAs corresponding to mouse homologs of deltex - mouse Deltex1 (MDTX1), mouse Deltex2 (MDTX2), mouse Deltex2DeltaE (MDTX2DeltaE), and mouse Deltex3 (MDTX3). Deduced amino acid sequences of these four cDNAs showed a high degree of similarity to Drosophila Deltex and its human homolog, DTX1 throughout their lengths, even though they possess distinct structural features. MDTX proteins formed homotypic and heterotypic multimers. We found that these genes were expressed in the central, peripheral nervous system and in the thymus, overlapping with those of mouse Notch1. In mammalian tissue culture cells, overexpression of any of the four mouse deltex homologs suppressed the transcriptional activity of E47, a basic helix-loop-helix (bHLH) protein, in a manner similar to suppression by an activated form of human Notch1 or human DTX1. In addition, overexpression of MDTX2 and MDTX2DeltaE in C2C12 cells under differentiation-inducing conditions suppressed the expression of myogenin, one of the myogenic transcriptional factors; this was also similar to a previously reported activity of constitutively activated Notch. Furthermore, misexpression of any of the MDTX genes in Xenopus embryos resulted in an expansion of the region expressing the neural cell adhesion molecule (N-CAM) gene, a marker for the neuroepithelium. Collectively, our results suggest that these mouse deltex homologs are involved in vertebrate Notch signaling and regulation of neurogenesis.

Amino Acid Sequence↗
PubMed2001

Enhancement of bone morphogenetic protein-2-induced new bone formation in mice by the phosphodiesterase inhibitor pentoxifylline.

Porous collagen disks (6 mm diameter, 1 mm thickness) were impregnated with recombinant human bone morphogenetic protein-2 (rhBMP-2) (5 microg/disk) and implanted onto the back muscles of mice. Pentoxifylline (PTX), which is a methylxanthine-derived inhibitor of phosphodiesterases (PDEs), or vehicle, was injected (5, 25, 50, 100, 200, and 300 mg/kg body weight/day) into the mice subcutaneously once a day for 3 weeks from the day of implantation of the bone morphogenetic protein (BMP)-laden disks. The rhBMP-2-induced ectopic ossicles were harvested and examined using radiographic, histological, and biochemical methods to determine size, bone quality, and calcium content. When compared with controls, ossicles from mice treated with >50 mg/kg per day of PTX were significantly larger in size and had a greater calcium content. However, no differences were noted in mice treated with lower doses (5 and 25 mg/kg per day) of PTX. The temporal sequence of the bone-forming process was unchanged by PTX based on histological examination. The histology of the ossicles from high- and low-dose PTX-treated mice was essentially identical to that observed in the control mice. These experimental results indicate that PTX enhanced the bone-inducing capacity of BMP-2. The underlying mechanism of action most likely involves the inhibition of intracellular phosphodiesterases and a resulting elevation of the intracellular content of cyclic nucleotides. Further studies are warranted to understand how BMP-induced bone formation is pharmacologically modified by PTX.

Animals↗
PubMed2001

Comparison of immunoperoxidase plaque staining and neutralizing tests for canine distemper virus.

The use of immunoperoxidase plaque staining (IP) in the antibody test for canine distemper virus (CDV) and its diagnostic value were investigated. Antibody titres by the IP test and neutralizing test (NT) against CDV were compared in 114 specific pathogen-free (SPF) dogs, including 84 CDV-vaccinated and 30 unimmunized dogs. All of the unimmunized dogs, which had negative NT titres, also showed negative IP titres, and all of the CDV-vaccinated dogs, which had positive NT titres, showed positive IP titres. Furthermore, the IP titres showed similar changes with time after vaccination to the NT titres in five CDV-vaccinated SPF dogs. These findings indicate that the IP test has similar specificity to the NT. Next, the IP and NT titres were compared in 190 clinically suspected cases of canine distemper (CD), including 107 dogs with neurological signs and 83 dogs without neurological signs, and also in 50 clinically healthy dogs. Among the suspected cases of CD, of 46 dogs with neurological signs and 29 dogs without neurological signs, and which had negative NT titres, 33 (72%) and 19 (66%), respectively, showed positive IP titres. Many suspected cases of CD showed a high IP titre despite a low NT titre. In contrast, among healthy dogs, none of 9 NT-negative dogs showed positive IP titres. The difference in the IP and NT titres (log10) [reciprocal of IP titre] - log10) [reciprocal of NT titre]) was measured to investigate the agreement between IP test and NT. The differences were 1.488 +/- 0.867, 1.245 +/- 0.833, 0.595 +/- 0.351 and 0.594 +/- 0.372, respectively, in the suspected cases of CD with neurological signs, the suspected cases of CD without neurological signs, the healthy dogs and the SPF dogs. The differences in the suspected cases of CD were significantly high compared to those for the SPF dogs (p < 0.001). Furthermore, in 8 dogs diagnosed as cases of CD from their paired sera, whose initial sera showed a markedly low NT titre compared to the IP titre, 5 dogs without neurological signs developed neurological signs later. These findings suggest that the IP test can detect CD during its early phases and in dogs with low antibody levels, undetectable by NT, and so would be useful for serological diagnosis.

Animals↗
PubMed2001

Hypermethylation of p16INK4A gene promoter during the progression of plasma cell dyscrasia.

Recent studies have indicated a close relationship between inactivation of tumor suppressor genes (TSGs) and disease progression. The genes encoding the cyclin-dependent kinase inhibitors p16INK4A and p15INK4B are potent TSGs, and correlations between their inactivation and disease progression have also been reported in various malignancies. In this study, we analyzed the methylation status of p16INK4A and p15INK4B gene promoters in plasma cell dyscrasias (PCDs) by methylation-specific PCR (MSP). In analyses using DNAs extracted from bone marrow mononuclear cells (BM-MNCs), patients with multiple myeloma (MM) showed frequent hypermethylation of the p16INK4A gene (15/37, 41%), whereas p15INK4B gene methylation was not so frequent (5/37, 14%). Many patients whose BM-MNC showed dense methylation of the p16INK4A gene had extramedullary plasmacytoma (extra-PC), and all available extra-PC samples showed alterations of the p16INK4A gene (4; dense methylation, 1; homozygous deletion). In contrast to MM, hypermethylation of the p16INK4A gene was significantly infrequent in indolent PCDs (2/22, 9%, P= 0.0055). The infrequency in indolent PCDs was also confirmed by analyses using DNAs extracted from BM smears (1/29, 3%). It is possible that hypermethylation of the p16INK4A gene promoter contributes to progression to aggressive MM from indolent PCD, especially to extra-PC development.

Biomarkers↗
PubMed2001

Xoom is maternally stored and functions as a transmembrane protein for gastrulation movement in Xenopus embryos.

Xoom has been identified as a novel gene that plays an important role in gastrulation of Xenopus laevis embryo. Although Xoom is actively transcribed during oogenesis, distribution and function of its translation product have not yet been clarified. In the present study, the polyclonal antibody raised against Xoom was generated to investigate a behavior of Xoom protein. Anti-Xoom antibodies revealed that there are two forms of Xoom protein in Xenopus embryos: (i) a 45 kDa soluble cytoplasmic form; and (ii) a 44 kDa membrane-associated form. Two forms of Xoom protein were ubiquitously detected from unfertilized egg to tadpole stage, with a qualitative peak during blastula and gastrula stages. Immunohistochemical examination showed that Xoom protein is maternally stored in the animal subcortical layer and divided into presumptive ectodermal cells during cleavage stages. Enzymatic digestion of membrane protein and immunologic detection of Xoom showed that Xoom exists as a membrane-associated protein. To examine a function of Xoom protein, anti-Xoom antibodies were injected into blastocoele of stage 7 blastula embryo. Anti-Xoom antibodies caused gastrulation defect in a dose- dependent manner. These results suggest that maternally prepared Xoom protein is involved in gastrulation movement on ectodermal cells.

Animals↗
PubMed2001

Facial nerve palsy: evaluation by contrast-enhanced MR imaging.

AIM: The purpose of this study was to investigate the value of contrast-enhanced magnetic resonance (MR) imaging in patients with peripheral facial nerve palsy. MATERIALS AND METHODS: MR imaging was performed in 147 patients with facial nerve palsy, using a 1.0 T unit. All of 147 patients were evaluated by contrast-enhanced MR imaging and the pattern of enhancement was compared with that in 300 control subjects evaluated for suspected acoustic neurinoma. RESULTS: The intrameatal and labyrinthine segments of the normal facial nerve did not show enhancement, whereas enhancement of the distal intrameatal segment and the labyrinthine segment was respectively found in 67% and 43% of patients with Bell's palsy. The geniculate ganglion or the tympanic-mastoid segment was enhanced in 21% of normal controls versus 91% of patients with Bell's palsy. Abnormal enhancement of the non-paralyzed facial nerve was found in a patient with bilateral temporal bone fracture. CONCLUSION: Enhancement of the distal intrameatal and labyrinthine segments is specific for facial nerve palsy. Contrast-enhanced MR imaging can reveal inflammatory facial nerve lesions and traumatic nerve injury, including clinically silent damage in trauma.

Adolescent↗
PubMed2001

Analysis of the phosphorylation level in guard-cell plasma membrane H+-ATPase in response to fusicoccin.

A fungal phytotoxin fusicoccin (FC) causes irreversible opening of stomata by activation of the plasma membrane H+-ATPase in guard cells. However, the mechanism by which FC activates the H+-ATPase is not fully understood with respect to the event of phosphorylation. In this study, we provide quantitative evidence that FC-dependent activation of H+-ATPase requires the phosphorylation of the C-terminus, and that FC maintains the activated state by preventing the dephosphorylation. The plasma membrane H+-ATPase in guard cells was phosphorylated on serine and threonine residues in the C-termini of both VHA1 and VHA2 by FC, and the phosphorylation level paralleled the rates of H+-pumping and ATP hydrolysis. An endogenous 14-3-3 protein was co-precipitated with the H+-ATPase, and the amount of 14-3-3 protein was proportional to the phosphorylation level of H+-ATPASE: The recombinant 14-3-3 protein bound to the C-terminus only when it was phosphorylated, even in the presence of FC. The phosphorylated C-terminus was dephosphorylated by alkaline phosphatase, and the dephosphorylation was completely prevented when the C-terminus had been incubated with both FC and 14-3-3 protein. The results suggest that FC activates the H+-ATPase by accumulating the complex of phosphorylated H+-ATPase and 14-3-3 protein through inhibition of the dephosphorylation in guard cells.

14-3-3 Proteins↗
PubMed2001

Guard-cell chloroplasts provide ATP required for H(+) pumping in the plasma membrane and stomatal opening.

To elucidate the role of guard-cell chloroplasts (GCCs) in stomatal movement, we investigated the effects of oligomycin, an inhibitor of oxidative phosphorylation, and 3-(3,4-dichlorophenyl)-1,1-dimethylurea (DCMU), an inhibitor of photosystem II, on fusicoccin (FC)-induced H(+) pumping and stomatal opening. FC was found to induce H(+ )pumping in guard-cell protoplasts (GCPs) from Vicia faba and stomatal opening in the epidermis of Commelina benghalensis; and, red light (RL) slightly stimulated these responses. Oligomycin strongly inhibited the pumping and stomatal opening in the dark. RL partially reversed the inhibitions, and DCMU decreased the effect of RL. FC activated the plasma membrane H(+)-ATPase (EC 3.6.1.35) in GCPs similarly irrespective of these treatments, indicating that the H(+)-ATPase activity was not the limiting step in H(+) pumping. Oligomycin significantly decreased the ATP content in GCPs in the dark. RL partially reversed this effect, and DCMU eliminated the effect of RL. A significant part of the ATP produced by photophosphorylation to H(+) pumping was indicated under RL. These results suggest that GCCs supply ATP to the cytosol under RL, and that the ATP is utilized by the plasma membrane H(+)-ATPase for H(+) pumping.

Cell Membrane↗
PubMed2001

Evaluation of thoracic myelopathy by transcranial magnetic stimulation.

It is sometimes difficult to determine the appropriate surgical site in patients with thoracic myelopathy with diffuse or multisegmental lesions. To solve this problem, a magnetic stimulation study was carried out. Seven patients with myelopathy and 10 healthy control subjects were examined. Transcranial magnetic stimulation was applied and the motor evoked potentials (MEPs) of the intercostal muscles were recorded. The MEP latencies for the two groups were then compared. In patients with thoracic myelopathy, the MEP latencies caudal to the lesion were more extended than those of the control subjects. This method could identify the levels at which myelopathy originates in patients with a radiologically visible lesion. This method has the potential to be used for deciding the surgical site at the level responsible for myelopathy in cases with multiple or diffused compression.

Adult↗
PubMed2001

Specific binding of vf14-3-3a isoform to the plasma membrane H+-ATPase in response to blue light and fusicoccin in guard cells of broad bean.

The plasma membrane H(+)-ATPase is activated by blue light with concomitant binding of the 14-3-3 protein to the C terminus in guard cells. Because several isoforms of the 14-3-3 protein are expressed in plants, we determined which isoform(s) bound to the H(+)-ATPase in vivo. Four cDNA clones (vf14-3-3a, vf14-3-3b, vf14-3-3c, and vf14-3-3d) encoding 14-3-3 proteins were isolated from broad bean (Vicia faba) guard cells. Northern analysis revealed that mRNAs encoding vf14-3-3a and vf14-3-3b proteins were expressed predominantly in guard cells. The 14-3-3 protein that bound to the H(+)-ATPase in guard cells had the same molecular mass as the recombinant vf14-3-3a protein. The H(+)-ATPase immunoprecipitated from mesophyll cell protoplasts, which had been stimulated by fusicoccin, coprecipitated with the 32.5-kD 14-3-3 protein, although three 14-3-3 isoproteins were found in mesophyll cell protoplasts. Digestions of the bound 14-3-3 protein and recombinant vf14-3-3a with cyanogen bromide gave the identical migration profiles on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, but that of vf14-3-3b gave a different profile. Mass profiling of trypsin-digested 14-3-3 protein bound to the H(+)-ATPase gave the predicted peptide masses of vf14-3-3a. Far western analysis revealed that the H(+)-ATPase had a higher affinity for vf14-3-3a than for vf14-3-3b. These results suggest that the 14-3-3 protein that bound to the plasma membrane H(+)-ATPase in vivo is vf14-3-3a and that it may play a key role in the activation of H(+)-ATPase in guard cells.

14-3-3 Proteins↗
PubMed2001

Purification, crystallization and preliminary X-ray diffraction analysis of the fructose-1,6-/sedoheptulose-1,7-bisphosphatase of Synechococcus PCC 7942.

Fructose-1,6-/sedoheptulose-1,7-bisphosphatase of Synechococcus PCC 7942, overexpressed from Escherichia coli, has been purified and crystallized by the hanging-drop vapour-diffusion method using ammonium sulfate as a precipitant. The crystals were monoclinic, with unit-cell parameters a = 80.1, b = 84.2, c = 104.3 A, beta = 101.7 degrees. They belonged to space group P2(1) and diffracted to at least 2.2 A resolution. The calculated V(M) value, based on a tetramer in the asymmetric unit, was 2.2 A(3) Da(-1).

Crystallization↗