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Biomedical subjects

T Nakabayashi

Publications and source records attributed to T Nakabayashi.

At least 19 recordsLinked to original sources
PubMed2006

Phase I/II study of S-1 combined with paclitaxel in patients with unresectable and/or recurrent advanced gastric cancer.

Both paclitaxel and S-1 are effective against gastric cancer, but the optimal regimen for combined chemotherapy with these drugs remains unclear. This phase I/II study was designed to determine the maximum tolerated dose (MTD), recommended dose (RD), dose-limiting toxicity (DLT), and objective response rate of paclitaxel in combination with S-1. S-1 was administered orally at a fixed dose of 80 mg m-2 day-1 from days 1 to 14 of a 28-day cycle. Paclitaxel was given intravenously on days 1, 8, and 15, starting with a dose of 40 mg m-2 day-1. The dose was increased in a stepwise manner to 70 mg m-2. Treatment was repeated every 4 weeks unless disease progression was confirmed. In the phase I portion, 17 patients were enrolled. The MTD of paclitaxel was estimated to be 70 mg m-2 because 40% of the patients given this dose level (two of five) had DLT. The RD was determined to be 60 mg m-2. In the phase II portion, 24 patients, including five with assessable disease who received the RD in the phase I portion, were evaluated. The median number of treatment courses was six (range: 1-17). The incidence of the worst-grade toxicity in patients given the RD was 28 and 8%, respectively. All toxic effects were manageable. The response rate was 54.1%, and the median survival time was 15.5 months. Our phase I/II trial showed that S-1 combined with paclitaxel is effective and well tolerated in patients with advanced gastric cancer.

Adult↗
PubMed2006

Possible association between nonsynonymous polymorphisms of the anaplastic lymphoma kinase (ALK) gene and schizophrenia in a Japanese population.

We examined, for the first time, the possible association between schizophrenia and the anaplastic lymphoma kinase (ALK) gene which plays an important role in neurodevelopment. When two nonsynonymous polymorphisms (Arg1491Lys and Glu1529Asp) were examined, there were significant differences in genotype and allele distributions between patients and controls. Individuals homozygous for the minor allele (1491Lys-1529Asp) were more common in patients than in controls (p = 0.0064, odds ratio 2.4, 95% CI 1.3-4.6). These results suggest that genetic variations of the ALK gene might confer susceptibility to schizophrenia.

Alleles↗
PubMed2006

Ghrelin does not stimulate gastrointestinal motility and gastric emptying: an experimental study of conscious dogs.

Ghrelin is a peptide that was discovered in endocrine cells of the stomach. However, its action in regulating the fasted and fed motor activity of the digestive tract is not fully understood. In the present study, we examined the effects of an intravenous (i.v.) injection of canine ghrelin on the physiological fasted and fed motor activities in the stomach, duodenum, jejunum and colon of freely moving conscious dogs. An i.v. injection of canine ghrelin released growth hormone in a dose-dependent manner; however, it did not stimulate the motor activity of the digestive tract in either the fasted or the fed state. Moreover, an i.v. injection of high-dose canine ghrelin significantly reduced the motility index in the gastric body in the fasted state. Ghrelin did not accelerate gastric emptying, either. These results differ from previous reports dealing with rodents. It is significant that such results were obtained in research with dogs, which are larger animals.

Animals↗
PubMed2005

Clinical significance of mucin phenotype, beta-catenin and matrix metalloproteinase 7 in early undifferentiated gastric carcinoma.

BACKGROUND: The aim of this study was to examine the clinical significance of mucin phenotypes of early undifferentiated gastric carcinoma, and to identify variables that might be used to select patients suitable for minimally invasive surgery. METHODS: A total of 129 patients with early undifferentiated gastric carcinoma were studied. The mucin phenotype was determined immunohistochemically using markers for M1, apomucin (MUC) 6 and MUC2. Tumours were classified into gastric (G), intestinal, gastrointestinal (GI) or unclassified type. Undifferentiated carcinomas were classified into signet-ring cell carcinoma (SIG) and non-SIG. The immunoreactivity of matrix metalloproteinase (MMP) 7 and beta-catenin was also investigated. RESULTS: GI-type tumours more commonly expressed non-SIG than SIG histology. The GI phenotype was associated with a higher incidence of submucosal invasion, lymphatic invasion, MMP-7 expression and nuclear accumulation of beta-catenin than the G type. Non-SIG histology, and the combination of GI type and nuclear accumulation of beta-catenin were independent predictors of submucosal invasion. The combination of GI type and MMP-7 expression independently predicted lymphatic invasion. MMP-7 expression correlated with lymph node metastasis. CONCLUSION: GI-type early undifferentiated carcinomas and those with non-SIG histology had increased potential for invasion and metastasis. GI type, MMP-7 expression and nuclear accumulation of beta-catenin might prove useful markers in the selection of patients for less invasive surgery.

Cytoskeletal Proteins↗
PubMed2004

Synthetic selective inhibitors of coagulation factor Xa strongly inhibit thrombin generation without affecting initial thrombin forming time necessary for platelet activation in hemostasis.

DX-9065a and JTV-803, synthetic selective inhibitors of activated factor X (FXa), have recently been demonstrated as strongly effective antithrombotic agents in animal thrombosis models, yet with a low risk of bleeding. The aim of the present study was to elucidate these characteristics. Using a chromogenic assay with purified coagulation factors, 73.9% of thrombin generation was suppressed by the addition of DX-9065a (0.20 microm) and 75.7% by JTV-803 (0.18 microm). Inhibition by argatroban (0.19 microm) was less (36.0%) and initial thrombin forming time (T50), the time required to generate 50% thrombin activity in vitro, which is considered important for platelet aggregation in hemostasis, was significantly prolonged by argatroban. In contrast, DX-9065a and JTV-803 had no apparent influence on T50, suggesting that initial thrombin was formed immediately, as in the control. We also investigated platelet aggregation in defibrinated plasma induced by tissue factor, to clarify whether initial thrombin contributes to hemostasis. Aggregation was not affected by the addition of either FXa inhibitor, whereas it was significantly reduced by argatroban. Our results suggest that initial thrombin, which is formed despite the presence of a FXa inhibitor, can activate platelets. We concluded that DX-9065a and JTV-803 are able to inhibit thrombin generation significantly without affecting the formation of initial thrombin for platelet activation, which may contribute to hemostasis through the preservation of normal bleeding time.

Anticoagulants↗
PubMed2001

Barostat examination of proximal site of the anastomosis in patients with rectal cancer after low anterior resection.

Patients who have undergone low anterior resection (LAR) of the rectum for cancer show symptoms of urgency and frequency of defecation after meals. The cause of these symptoms is unclear. It was hypothesized that the functional disorder of the proximal site of the anastomosis after low anterior resection of the rectum often leads to the symptoms and that the 5-HT3 receptor antagonist reduces postprandial colonic contractions. The aim of this study was to assess colon contractions of the proximal site of the anastomosis and the effects of the 5-HT3 receptor antagonist on the contractions. We evaluated 37 patients who had undergone LARs, 17 with high stool frequency (more than four times per day) and 20 with normal stool frequency. In the first part of the study, basal tone, compliance of the proximal site of the anastomosis, and response to a meal (300 kcal) were recorded with a barostat in all patients. In the second part of the study the effects of the 5-HT3 receptor antagonist on contractions of the proximal site of the anastomosis after ingesting a meal was evaluated. Seven healthy controls were also studied for descending colonic tone with a barostat after a meal. Basal barostat balloon volumes showed only small variations in the two post-LAR groups. Compliance of the proximal site of the anastomosis was similar in the two groups. Meal ingestion stimulated contractions of the proximal site of the anastomosis. In patients with high stool frequency the proximal site of the anastomosis contracted earlier than in those with normal stool frequency after a meal. The descending colonic tone of healthy controls did not change after a meal. The 5-HT3 receptor antagonist inhibited postprandial contractions of the proximal site of the anastomosis after LAR. These observations lend support to the idea that gastrocolonic reflex increases in patients who have undergone LAR, leading to high stool frequency. Furthermore, the 5-HT3 receptor antagonist may alleviate the symptoms of urgency and the frequency of defecation.

Adult↗
PubMed2001

TGF-beta1 null mutation leads to CD154 upregulated expression in affected tissues.

The TGF-beta1(-/-) mouse is a murine model for systemic autoimmune disease. The aim of this study is to elucidate the immunological mechanism that leads to multifocal tissue inflammation and autoantibody production in TGF-beta1(-/-) mice. Heart, lung, liver, and salivary gland from TGF-beta1(-/-) were assessed for CD154 expression by RT-PCR and immunohistochemistry. Compared to wild-type littermates, CD154 expression was elevated in all tissues studied. Furthermore, IL-12 mRNA was expressed in the salivary gland and heart of TGF-beta1(-/-) mice and not in wild-type littermates. This suggests that the CD154 pathway is activated in these tissues. This shows that TGF-beta1 regulates CD154 expression leading to spontaneous IL-12 production and autoimmunity.

Animals↗
PubMed2001

Pyloric relaxation regulated via intramural neural pathway of the antrum.

Current information about pyloric relaxation is not sufficient. For this reason, our study aimed at measuring pyloric relaxation correctly and determining the role of the intrinsic and extrinsic neural pathway in pyloric relaxation. Five groups of dogs were used: five dogs had an intact gastrointestinal tract (control group); five dogs had transection and reanastomosis of the antrum 3 cm proximal to the pylorus (antral transection group); five dogs had extrinsic pyloric denervation (denervation group); five dogs had transection and reanastomosis of the antrum with extrinsic pyloric ring denervation (transection with denervation group); and five dogs had truncal vagotomy (vagotomy group). Gastropyloroduodenal motility was recorded by a strain-gauge force transducer in conscious dogs. In the control and denervation groups, pyloric relaxation was observed only during phase III of the interdigestive migrating motor complex. In the antral transection, transection with denervation, and vagotomy groups, pyloric relaxation was not observed in either the interdigestive or the postprandial state. The frequency of pyloric contractions increased in these groups in comparison with the control group. In conclusion, the results suggest that pyloric relaxation occurred during phase III to expel undigested particles from the stomach and that descending antral intramural pathways play an important role in the control of pyloric relaxation.

Animals↗
PubMed2001

Laparoscopically assisted total or distal gastrectomy with lymph node dissection for early gastric cancer.

BACKGROUND: A secure lymphadenectomy in a laparoscopically assisted gastrectomy performed for gastric cancer is required because of the high prevalence of lymph node metastasis. A surgical technique for laparoscopic gastrectomy with lymph node dissection and reconstruction using a conventional circular stapler is reported. METHODS: Forty-nine laparoscopically assisted gastrectomies with lymphadenectomy (47 distal and two total gastrectomies) were performed using devices for retraction of the stomach and laparoscopic ligation of arteries, which were developed to ensure secure dissection of lymph nodes. Reconstruction by Billroth I or intestinal interposition using a conventional circular stapler was performed through a small incision through which the specimen was removed. When submucosal invasion was suspected (n = 16), the lymph nodes along with the common hepatic artery were also dissected through the same incision. RESULTS: The operations were performed without serious complication. None was converted to laparotomy, and there were no deaths. Metastatic lymph nodes were seen in perigastric nodes and nodes along the left gastric artery in five cases. In five of the 49 patients the macroscopic diagnosis of depth of invasion was underestimated. CONCLUSION: A technique of laparoscopic gastrectomy with lymph node dissection for early invasive gastric cancer is described. A definitive answer concerning the appropriate level of lymph node dissection and the role of laparoscopic gastrectomy in the treatment of more advanced gastric cancer remains to be defined.

Adult↗
PubMed2001

Absence of sleep spindles in human medial and basal temporal lobes.

All-night recordings from subdural electrocorticographic (ECoG) electrodes on the human medial and basal temporal lobes were analysed to examine spindling activities during sleep. Subjects were three males and three females who were candidates for neurosurgical treatments of partial epilepsy. Subdural electrodes were attached to the medial and basal temporal lobe cortices, allowing ECoG and electroencephalogram from the scalp vertex (Cz EEG) to be recorded simultaneously during all night sleep. In one case, subdural electrodes were attached also on the parietal lobe. Fast Fourier transformation (FFT) analyses were performed on the ECoG and Cz EEG signals. No organized sleep spindles or sigma band (12-16 Hz) peaks in FFT power spectra were observed from the medial or basal temporal lobes of the non-epileptogenic hemispheres during non-rapid eye movement (NREM) sleep. In a case with parietal electrodes, organized spindle bursts were observed in parietal signals synchronized with Cz spindles. Although delta band (0.3-3 Hz) power from both the medial and basal temporal lobes fluctuated across each night as expected, sigma activity changed little. However, 14 Hz oscillatory bursts were observed in the medial basal temporal lobe of epileptogenic hemisphere in two cases and bilaterally in one case during not only NREM sleep but rapid eye movement (REM) sleep and wakefulness. From the present study we conclude that sleep spindle activities are absent in the medial and basal temporal lobes. Fourteen Hz oscillatory bursts observed from the medial or basal temporal lobe in some cases were not considered to be sleep spindles since they also appeared during REM sleep and wakefulness. These waveforms could have originated due to epileptic pathology, since they frequently appeared in epileptic regions.

Adult↗
PubMed2001

Skin antigens in the steady state are trafficked to regional lymph nodes by transforming growth factor-beta1-dependent cells.

Antigen capturing in the skin and antigen trafficking into regional lymph nodes (LN) initiate immune responses. In this study, employing melanin granule (MG) as an easily traceable antigen in two mouse strains that carried steel factor or hepatocyte growth factor transgenes and had melanocytosis in the epidermis or in the dermis respectively, we investigated the mechanism of antigen trafficking from the skin. MG captured in the epidermis or dermis accumulated in the regional LN, but not other tissues. Only in alymphoplastic mice did MG-laden cells pass through the lymphatics and reached many tissues. Since inflammatory regions were not observed in the skin of either type of transgenic mouse, our developmental system enables us to investigate constitutive capturing and trafficking of insoluble antigens in the steady state. Both dendritic cells and macrophages were laden with MG in the regional LN. To determine which cells traffic antigens to the LN, we prepared double mutants that carried the transgenes and lacked transforming growth factor (TGF)-beta1, since mice lacking TGF-beta1 are reported to be deficient of Langerhans cells. Few MG were observed in the regional LN of these double-mutant mice. We also showed that signaling via macrophage colony stimulating factor receptor or Flt3/Flk2 is not essential for development of the cells for this antigen trafficking. These results indicate that antigens in the epidermis and dermis in the steady state are trafficked into regional LN only by TGF-beta1-dependent cells, which may be a dendritic cell lineage.

Animals↗
PubMed2001

Pharmacokinetics of granisetron in adults and children with malignant diseases.

Granisetron (GRN) is widely used for patients with various cancers who suffer from chemotherapy-induced vomiting and nausea. The, pharmacokinetics of GRN has not been fully evaluated in such patients, however, and its dosage regimen is still controversial. In this study, we determined GRN levels in serum and urine from lung cancer patients and children suffering from cancer after intravenous infusion. In lung cancer patients, the interindividual variations in t(1/2beta), area under the concentration-time curve (AUC), and Vd(beta) were relatively smaller than expected from previous reports on healthy subjects, while t(1/2beta) was prolonged more than 5-fold in healthy subjects. Urinary excretion of unchanged GRN in lung cancer patients was ca. 15% of dose, consistent with previous reports, and one individual demonstrated an even higher urinary excretion (ca. 45%). The pharmacokinetic parameters of GRN in child cancer patients varied markedly among individuals, and some child patients had smaller t(1/2beta) than adult patients. In these cases, GRN should be administered at shorter intervals. These results suggested that a pharmacokinetic study of GRN was necessary for planning a dosage regimen and managing chemotherapy-induced vomiting and nausea.

Adolescent↗
PubMed2001

Evaluation of the automatic fluorescent image analyzer, Image Titer, for quantitative analysis of antinuclear antibodies.

By making comparisons with the usual manual method, we evaluated an automatic fluorescent image analyzer (Image Titer, Tripath Imaging, Burlington NC), the software for which was developed to simplify measuring indirect immunofluorescent antinuclear antibodies (FANAs). In this new system, images of the stained sample are displayed, and it measures the FANA titer and staining pattern using only 1 slide per subject and does not required the staining of a series of diluted samples as does the manual method. This system showed good reproducibility and linearity for 4 types of control serum samples (with homogeneous, speckled, discrete speckled, and nucleolar staining patterns). In 132 serum samples, consistency between the methods was 100% for the FANA staining pattern and 93.9% for the FANA titer. The Image Titer system detected each pattern in samples with 2 mixed patterns. This system should partly reduce labor and lead to results with minimum differences among individuals, including newly trained persons.

Antibodies, Antinuclear↗
PubMed2001

Confirmation of minor components of less polar neutral and acidic glycolipids in monkey brain tissue.

Crude glycolipids, prepared without alkali treatment in advance, were separated into neutral and acidic glycolipids by DEAE-Sephadex A-25 (acetate form) column chromatography. Each glycolipid was further fractionated by a Silica gel 60-column chromatography. By matrix-assisted laser desorption/ionization time-of-flight mass spectrometry with delayed ion extraction (DE MALDI-TOF MS) of the intact glycolipid fractions, the less polar neutral glycolipids were found to contain alkali-labile ester cerebrosides and Galb-1-Diradylglycerols, whereas the less polar acidic glycolipids were found to contain alkali-labile ester sulfatide, HSO(3)-3Gal-1-Diradylglycerols, and novel alkali-stable plasmalo-sulfatides and ester or plasmalo HSO(3)-3Galb-1-Diradylglycerols as minor components of glycolipids in monkey brain tissue. In conclusion, minor components of less polar neutral and acidic glycolipids in monkey brain tissue were confirmed as ester cerebrosides, Galb-1-Diradylglycerols, ester sulfatides, HSO(3)-3Galb-1-Diradylglycerols, and novel plasmalo-sulfatides and ester or plasmalo HSO(3)-3Galb-1-Diradylglycerols by DE MALDI-TOF MS.

Animals↗
PubMed2000

Effect of apolipoprotein AII on the interaction of apolipoprotein E with beta-amyloid: some apo(E-AII) complexes inhibit the internalization of beta-amyloid in cultures of neuroblastoma cells.

Apolipoprotein (apo) E and its polymorphism are linked to the pathogenesis of late-onset and sporadic Alzheimer's disease (AD). ApoE facilitates the deposition and fibrillogenesis of beta-amyloid (Abeta), and may participate in Abeta clearance. We recently found that apo(E-AII) complex binds to Abeta much more strongly than does monomeric apoE. Here, we investigated the effect of apoAII on the interaction between apoE and Abeta. Addition of apoAII to apoE monomers increased the binding of apoE2 and apoE3 to Abeta(1-42), presumably following the formation of apo(E3-AII), apo(E2-AII), and apo(AII-E2-AII) complexes. This increased binding was not seen in the case of apoE4. When neuroblastoma cells were cultured in media containing Abeta(1-42) and a mixture of apoE3 and apoAII, intracellular Abeta was significantly reduced and cell viability was maintained at a higher level than in cells cultured without apoAII. ApoE2 itself seemed to act as an inhibitor of the endocytosis of Abeta, and we did not observe a significant effect of apoAII on the movement of Abeta in apoE2-containing medium. However, cell viability could be maintained at a higher level (as with apoE3) by adding apoAII to apoE2, despite the reduced viability of cells incubated without apoAII. In medium containing apoE4, both the amount of Abeta accumulated into cells and the cell viability were unchanged by the presence of apoAII in the medium. In addition, apoE4 itself was toxic, as previously suggested. These findings demonstrate that the type of apo(E-AII) complex present could underlie the isoform-specific role of apoE in the pathogenesis of AD.

Alzheimer Disease↗
PubMed2000

Isolation of antigen from the circulating immune complex in mice infected with Plasmodium berghei.

Circulating immune complex (CIC) is known to play a role in pathological glomerular alterations in malaria. However, the nature of the antigens comprising the CIC is still not fully understood. We report here the isolation of the antigen in CIC and its localisation in mice infected with Plasmodium berghei NK65. The antigen was successfully isolated from CIC extracted from the blood of mice infected with P. berghei, by using C1q-coated microplates. The molecular mass of the antigen separated from CIC bound to C1q was found to be 78 kDa. Furthermore, localisation of the antigen was examined by the fluorescent antibody technique and immunoelectron microscopy. The antigen was detected in the parasitised erythrocyte and the mesangial matrix by both methods. These results suggest that the 78 kDa protein might be associated with the glomerular alterations in malaria infection.

Animals↗
PubMed2000

Suppression of gamma activity in the human medial temporal lobe by sevoflurane anesthesia.

We have reported the presence of continuous gamma (30-150 Hz) activity in the human medial temporal lobe (MTL). Since the MTL is involved in learning and memory, we speculated that MTL gamma activity is related to such higher brain functions. It is thus of interest to learn how this activity changes during different states of consciousness. In this study, we recorded electrocorticographic (ECoG) activity directly from the surface of the MTL after various doses of sevoflurane anesthesia. Five epileptic patients underwent electrode placement operations in which electrodes were attached to the surfaces of the MTL and the basal temporal lobe (BTL). Immediately following the operation ECoG was recorded from each patient under four concentrations of sevoflurane anesthesia (1.5, 2.0, 2.5 and 3.0%). Fast Fourier Transform (FFT) analysis was performed on the MTL ECoGs. Under the lowest sevoflurane concentration, MTL gamma activity was observed in all patients. However, gamma activity was progressively suppressed by increased concentrations of sevoflurane, in a dose-dependent manner. Sevoflurane has been known to reduce neuronal excitability in the rat hippocampus in vitro, probably by changing GABAergic inhibition. The reduction of MTL gamma in the present study may be the result of such a mechanism. Although memory function was not tested in this study, the amount of MTL gamma activity may be related to residual memory function during anesthesia.

Adolescent↗