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Biomedical subjects

K Kobayashi

Publications and source records attributed to K Kobayashi.

At least 19 recordsLinked to original sources
PubMed2007

Surgical resection of solitary adrenal metastasis from esophageal carcinoma following esophagectomy.

The prognosis of esophageal carcinoma following esophagectomy is poor due to a high frequency of metastasis to periesophageal lymph nodes and distant organs. However, we experienced a case with good prognosis following resection of a solitary adrenal metastatic tumor. The patient was a 70-year-old man diagnosed with type 2 esophageal cancer (Lt-Ae, T2N1M0, Stage IIB) who was treated with esophagectomy. Eight months following surgery, solitary adrenal metastasis was detected by CT, and was resected. At 42 months follow-up he has had a good quality of life in the community without evidence of recurrence. To the best of our knowledge, only five cases with resected solitary adrenal metastases including our case, have been reported, and show a greater than 1-year survival. Consequently, we suggest that resection of solitary organ metastases is a good alternative, even following esophagectomy.

Adrenal Gland Neoplasms↗
PubMed2006

Radiation-induced gamma-H2AX in mammalian cells irradiated with a synchrotron X-ray microbeam.

In order to study the radiobiological effects from low dose radiation, a cell irradiation system using synchrotron X-ray microbeam has been developed, by which cells can be recognised individually and irradiated one by one with the desired dose of monochromatic X rays. The minimum beam sizes obtained are 2 microm with the focusing optics and 5 microm square with the non-focused beam, and the beam size can be changed easily with a high-precision slit in the case of a non-focused beam. Human fibroblast cells were individually irradiated with this system, and immunostained by gamma-H2AX antibody to visualise the DNA damage. Most of the fluorescent foci were observed in a localised area in cell nuclei, the size of which was almost the same as the beam size.

Cells, Cultured↗
PubMed2006

Mitotic arrest caused by an X-ray microbeam in a single cell expressing EGFP-aurora kinase B.

Although the highest radiosensitivity of cells in the M phase among the other cell phases, such as the G(1), S and G(2) phases, has been known, the exact mechanism of radiosensitivity in mitotic cells remains unclear. Recently, mitotic arrest caused by DNA-damaging reagents has been shown, and the molecular mechanism in the arrest has been discussed in detail. In this study, abnormal cell-cycle progression in the M phase was investigated when a single mitotic cell in each mitotic stage was irradiated with a 5.35 keV X-ray microbeam focused on the cell nucleus. An X-ray microbeam irradiation system installed at BL-27 in Photon Factory, High Energy Accelerator Research Organization (HEARO, Tsukuba) was used. HeLa cells, genetically modified and expressing enhanced green fluorescent protein-tagged aurora kinase B, were used as irradiated samples in order to recognise the stage of each cell in the M phase. Thus, 10 Gy irradiation concentrated at the nucleus of a single cell elongated the cell-cycle progression in the M phase by delaying the metaphase/anaphase transition. The dose dependence of the elongation of the M phase was also examined. An irregular distribution of DNA in anaphase cells was observed after irradiation.

Aurora Kinase B↗
PubMed2006

Bidirectional regulation of dopamine D2 and neurotensin NTS1 receptors in dopamine neurons.

Several lines of evidence suggest a close association between dopamine (DA) and neurotensin (NT) systems in the CNS. Indeed, in the rodent brain, abundant NT-containing fibres are found in DA-rich areas such as the ventral tegmental area and substantia nigra. Moreover, it has been shown in vivo that NT, acting through its high-affinity receptor (NTS1), reduces the physiological and behavioural effects of DA D2 receptor (D2R) activation, a critical autoreceptor feedback system regulating DA neurotransmission. However, the mechanism of this interaction is still elusive. The aim of our study was thus to reproduce in vitro the interaction between D2R and NTS1, and then to characterize the mechanisms implicated. We used a primary culture model of DA neurons prepared from transgenic mice expressing green fluorescent protein under the control of the tyrosine hydroxylase promoter. In these cultures, DA neurons endogenously express both D2R and NTS1. Using electrophysiological recordings, we show that activation of D2R directly inhibits the firing rate of DA neurons. In addition, we find that NT, acting through a NTS1-like receptor, is able to reduce D2R autoreceptor function independently of its ability to enhance DA neuron firing, and that this interaction occurs through a protein kinase C- and Ca(2+)-dependent mechanism. Furthermore, prior activation of D2R reduces the ability of NTS1 to induce intracellular Ca(2+) mobilization. Our findings provide evidence for bidirectional interaction between D2R and NTS1 in DA neurons, a regulatory mechanism that could play a key role in the control of the activity of these neurons.

Action Potentials↗
PubMed2006

Gefitinib for non-small-cell lung cancer patients with epidermal growth factor receptor gene mutations screened by peptide nucleic acid-locked nucleic acid PCR clamp.

This study was prospectively designed to evaluate a phase II study of gefitinib for non-small-cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations. Clinical samples were tested for EGFR mutations by peptide nucleic acid-locked nucleic acid PCR clamp, and patients having EGFR mutations were given gefitinib 250 mg daily as the second treatment after chemotherapy. Poor PS patients omitted chemotherapy. Of 107 consecutive patients enrolled, samples from 100 patients were informative, and EGFR mutations were observed in 38 patients. Gefitinib was given to 27 patients with EGFR mutations, and the response rate was 78% (one complete response and 20 partial responses; 95% confidence interval: 58-93%). Median time to progression and median survival time (MST) from gefitinib treatment were 9.4 and 15.4 months, respectively. Grade 3 hepatic toxicity and skin toxicity were observed in one patient each. There were significant differences between EGFR mutations and wild-type patients in response rates (78 vs 14%, P = 0.0017), and MST (15.4 vs 11.1 months, P = 0.0135). A Cox proportional hazards model indicated that negative EGFR mutation was a secondary prognostic factor (hazards ratio: 2.259, P = 0.036). This research showed the need for screening for EGFR mutations in NSCLC patients.

Adult↗
PubMed2006

Measurement of atmospheric neutrino flux consistent with tau neutrino appearance.

A search for the appearance of tau neutrinos from nu(mu) <--> nu(tau) oscillations in the atmospheric neutrinos has been performed using 1489.2 days of atmospheric neutrino data from the Super-Kamiokande-I experiment. A best fit tau neutrino appearance signal of 138+/-48(stat)-32(+15)(syst) events is obtained with an expectation of 78+/-26(syst). The hypothesis of no tau neutrino appearance is disfavored by 2.4 sigma.

Journal Article↗
PubMed2006

Ischaemic stroke with malignancy may often be caused by paradoxical embolism.

BACKGROUND: Although ischaemic stroke with malignancy occasionally occurs, the mechanisms of stroke in such cases have not been investigated in detail. OBJECTIVE: To examine the mechanisms of ischaemic stroke with malignancy, particularly in relation to right-to-left shunt (RLS). METHODS: Consecutive patients with ischaemic stroke within 24 h of stroke onset were prospectively studied. Contrast saline transcranial Doppler examination was carried out for all patients, to investigate the presence of RLS. When patients with stroke had RLS, deep venous thrombosis (DVT) or pulmonary embolism was assessed to diagnose paradoxical brain embolism. RESULTS: Participants comprised 184 consecutive patients (115 men and 69 women) with a mean (standard deviation (SD)) age of 73 (11.8) years and mean (SD) National Institutes of Health Stroke Scale (NIHSS) score of 8 (7.4). RLS was detected in 32 of 184 (18%) patients. Malignancy was present in 11 (5%) patients. RLS was more frequent in patients with malignancy than in patients without malignancy (55% v 15%, respectively; p = 0.001). All six patients with RLS and malignancy displayed DVT or pulmonary embolism with severe disability (modified Rankin Scale 4-5) before stroke onset. CONCLUSION: Paradoxical brain embolism should be considered to be an important mechanism in patients with stroke and malignancy.

Aged↗
PubMed2006

Improved search for nu(mu) --> nu(e) oscillation in a long-baseline accelerator experiment.

We performed an improved search for nu(mu) --> nu(e) oscillation with the KEK to Kamioka (K2K) long-baseline neutrino oscillation experiment, using the full data sample of 9.2 x 10(19) protons on target. No evidence for a nu(e) appearance signal was found, and we set bounds on the nu(mu) --> nu(e) oscillation parameters. At Deltam(2)=2.8 x 10(-3) eV(2), the best-fit value of the K2Knu(mu) disappearance analysis, we set an upper limit of sin(2)2theta(mue) < 0.13 at a 90% confidence level.

Journal Article↗
PubMed2006

Noxious cold stimulation induces mitogen-activated protein kinase activation in transient receptor potential (TRP) channels TRPA1- and TRPM8-containing small sensory neurons.

Two cold-sensitive transient receptor potential (TRP) channels, TRPA1 and TRPM8, have been identified and considered interesting because of their possible roles in thermosensation, nociception and other functions. Recently, we have reported that the phosphorylation of extracellular signal-regulated protein kinase and p38 mitogen-activated protein kinase occurred in primary afferent neurons in response to noxious heat stimulation of the peripheral tissue, i.e. activity-dependent activation of extracellular signal-regulated protein kinase and p38 in dorsal root ganglion neurons. In the present study, we investigated the phosphorylation of extracellular signal-regulated protein kinase, p38, and c-Jun N-terminal kinase in the rat dorsal root ganglion by cold stimulation using immunohistochemistry. Cold stimuli (28-4 degrees C) were applied by immersion of the hind paw into a water bath (six times of 10 s stimulation and 10 s interval, total 2 min). Noxious cold stimulation induced phosphorylated-extracellular signal-regulated protein kinase and phosphorylated-p38, but not phosphorylated-c-Jun N-terminal kinase, in small to medium diameter sensory neurons with a peak at 2 min after stimulation. We found that a cold stimulation at 4 degrees C showed a marked increase in the number of activated neurons. Furthermore, double staining for phosphorylated-extracellular signal-regulated protein kinase and phosphorylated-p38 showed no colocalization in the dorsal root ganglion neurons. We then performed double-labeling experiments for TRPA1 and TRPM8 mRNA and phosphorylation of mitogen-activated protein kinase. The majority of phosphorylated-extracellular signal-regulated protein kinase-positive neurons also expressed TRPM8 mRNA, whereas phosphorylated-p38 heavily colocalized with TRPA1 mRNA after noxious cold stimulation. Our data suggest that the noxious, but not innocuous, cold stimulation in vivo induced differential activation of extracellular signal-regulated protein kinase and p38 pathways in each subpopulation containing TRPA1 or TRPM8 in dorsal root ganglion.

Animals↗
PubMed2006

Electric-field effect on the angle-dependent magnetotransport properties of quasi-one-dimensional conductors.

We report a novel electric field effect on angular dependent magnetotransport in quasi-one-dimensional layered conductors with a pair of sheetlike Fermi surfaces. Under tilted magnetic fields and additional interlayer electric fields, semiclassical electron orbits on two Fermi sheets become periodic at different magnetic field orientations. This causes double splitting of the Lebed's commensurability resonance in interlayer transport, and the amount of splitting allows us to estimate the Fermi velocity directly. We have successfully demonstrated this effect in the organic conductor alpha-(BEDT-TTF)2KHg(SCN)4.

Journal Article↗
PubMed2006

Cutaneous infiltration with Waldenström macroglobulinemia.

A 59-year-old Japanese man was diagnosed as Waldenström macroglobulinema. With impaired general performance and a 2-year history of pruritic eruptions that were initially confined to the forearms, but later involved the face, limbs, and trunk. A skin biopsy that was performed on the forehead showed infiltration with abnormal cells of the dermis around the central vessels. PCR analysis of the skin biopsy showed immunoglobulin heavy chain rearrangement. As the rearrangement band occurred at the same site as that of the bone marrow aspiration, skin infiltration with abnormal cells was proven.

Asian People↗
PubMed2006

Identification of tumor markers and differentiation markers for molecular diagnosis of lung adenocarcinoma.

To identify tumor markers and differentiation markers for lung adenocarcinoma (AdC), we analysed expression profiles of 14,500 genes against three cases of type II alveolar epithelial cells, bronchiolar epithelial cells, and bronchial epithelial cells, respectively, and 10 cases of AdC cells isolated by laser capture microdissection. Hierarchical clustering analysis indicated that AdC cells and noncancerous lung epithelial cells are significantly different in their expression profiles, and that different sets of differentiation markers are expressed among alveolar, bronchiolar and bronchial epithelial cells. Nine genes were identified as being highly expressed in AdC cells, but not expressed in noncancerous lung epithelial cells. Sixteen genes were identified as differentiation markers for lung epithelial cells. Real-time RT-PCR analysis of 45 lung AdC cases further revealed that expression of four tumor markers in AdC cells was significantly higher than that in noncancerous lung cells and that expression of ten differentiation markers was retained in a considerable fraction of lung AdC cases. Five tumor markers and seven differentiation markers were not expressed in peripheral blood cells. Similarities and differences in expression profiles between normal epithelial cells from different lung respiratory compartments and AdC cells demonstrated in this study will be informative for the molecular diagnosis of lung AdC.

Adenocarcinoma↗
PubMed2006

MiniX-STR multiplex system population study in Japan and application to degraded DNA analysis.

We sought to evaluate a more effective system for analyzing X-chromosomal short tandem repeats (X-STRs) in highly degraded DNA. To generate smaller amplicon lengths, we designed new polymerase chain reaction (PCR) primers for DXS7423, DXS6789, DXS101, GATA31E08, DXS8378, DXS7133, DXS7424, and GATA165B12 at X-linked short tandem repeat (STR) loci, devising two miniX-multiplex PCR systems. Among 333 Japanese individuals, these X-linked loci were detected in amplification products ranging in length from 76 to 169 bp, and statistical analyses of the eight loci indicated a high usefulness for the Japanese forensic practice. Results of tests on highly degraded DNA indicated the miniX-STR multiplex strategies to be an effective system for analyzing degraded DNA. We conclude that analysis by the current miniX-STR multiplex systems offers high effectiveness for personal identification from degraded DNA samples.

Asian People↗
PubMed2006

Significant correlations between the flow volume of patent ductus venosus and early neonatal liver function: possible involvement of patent ductus venosus in postnatal liver function.

BACKGROUND: The biochemical features of portosystemic venous shunt with high flow volume are hypergalactosaemia, hyperammonaemia, prolonged blood coagulation time, and raised serum bile acid concentration. The ductus venosus remains open with shunt flow in most neonates for a certain period after birth. However, the effects of blood flow through the ductus venosus on neonatal liver function remain unclear. OBJECTIVE: To elucidate the effect of patency of the ductus venosus on liver function in early neonates. METHODS: Subjects were divided into three groups by gestational age (group I, 29-32 weeks; group II, 33-36 weeks; group III, 37-41 weeks). The shunt flow volume through the ductus venosus was examined serially using ultrasonography, and correlations between flow volume and liver function in the respective groups were calculated during the first week after birth. RESULTS: Group I had a higher flow volume and later functional closure than the other two groups. Plasma ammonia and serum total bile acid concentrations correlated with flow volume in groups I and II, and blood galactose and galactose 1-phosphate concentrations correlated significantly with flow volume in group III. Percentage hepaplastin also correlated significantly with flow volume in all groups, but plasma vitamin K concentration did not in any group. CONCLUSIONS: Patent ductus venosus has a considerable effect on crucial liver functions such as ammonia detoxification, blood coagulation, and regulation of serum total bile acid concentration in early neonates.

Ammonia↗
PubMed2006

Morphology control of poly(vinylidene fluoride) thin film made with electrospray.

Thin polymer films of poly(vinylidene fluoride) were prepared with electrospray. Effects of solvent, initial spray concentration, temperature, solution conductivity, and polymer size on the film morphology were studied with AFM. The two main factors controlling polymer film morphology are the droplet size of the spray and the viscosity of the solution at deposition. These factors determine the flow of the polymer-solvent mixture over the substrate, the density of the film, and its smoothness. The solvent is a key parameter of the entire process. It affects spray stability, polymer solubility, droplet size of the spray, and viscosity of the solution at deposition. Solvents with a low vapor pressure provide a wider window for optimization of other parameters and are therefore preferred over solvents with high vapor pressure. The viscosity at deposition is mainly controlled with the initial spray concentration, polymer size, temperature, and droplet size. The droplet size is best controlled by the conductivity of the solution and the flow rate of the spray.

Journal Article↗
PubMed2006

Therapeutic implications of the specific inhibition of causative matrix metalloproteinases in experimental colitis induced by dextran sulphate sodium.

Extracellular matrix dynamics, crucial for tissue remodelling, are highly regulated by a cascade of matrix metalloproteinases (MMPs) during inflammation and wound healing processes in inflammatory bowel disease (IBD). Contrary to expectations, there are limited reports to date that MMP inhibitors have some beneficial therapeutic effects in experimental colitis models. Furthermore, clinical trials of MMP inhibitors against certain tumours have failed to show any therapeutic benefit. One major reason for this lack of success may be the apparent uncertainty about the precise spectrum of inhibitory activity required. Since tumour necrosis factor alpha (TNFalpha), a key mediator in colonic inflammation, promotes MMP production in a dose-dependent manner, the therapeutic success of anti-TNFalpha agents against IBD motivated us to re-evaluate the therapeutic potential of MMP inhibition. First, using a quantitative polymerase chain reaction (PCR), western blotting, and zymography, we determined which MMPs were relevant to experimental colitis induced in mice by dextran sulphate sodium. Next, we examined a distinct role for MAPK and NFkappaB signalling pathways in the regulation of the expression of these MMP genes. Finally, we examined whether transcriptional regulation of these MMPs, either indirectly using inhibitors of MAPK and/or NFkappaB signalling pathways or directly using siRNA directed against these MMPs, contributes to the prevention of colitis. Changes in the expression level of colonic MMP-3 and MMP-10 preceded the clinical course of colitis. Colitis improved in mice that received these signal inhibitors, together with suppression of MMP expression. Moreover, siRNA that targeted MMP-3 and MMP-10 effectively reduced both the transcription of these MMPs and the severity of colitis. We conclude that MMP-3 and MMP-10 play a causal role in excess tissue destruction in colitis. Specific inhibition of these MMPs should provide novel therapeutics against IBD.

Animals↗
PubMed2006

Cytokine production profile of splenocytes derived from zymosan A-treated SKG mice developing arthritis.

OBJECTIVE: SKG mice have a point mutation of the zeta-associated protein of 70 kD (ZAP-70) and spontaneously develop a severe polyarthritis in the conventional condition, whereas they are healthy under the specific pathogen free (SPF) condition. The purpose of this study was to investigate the cytokine production from splenocytes in SKG mice developing arthritis under the SPF condition. MATERIAL: SKG and BALB/c mice were intraperitoneally injected with zymosan A under the SPF condition. Spleen was isolated 1, 2 or 8 weeks after the intraperitoneal injection of saline or zymosan A. Splenocytes were cultured with concanavalin A. Cytokine production and proliferation were measured 48 and 72 h after the culture. RESULTS: An intraperitoneal injection of zymosan A induced severe polyarthritis with increased levels of rheumatoid factor and interleukin 6 (IL-6) only in SKG mice. Splenocytes from SKG mice did not proliferate well maybe because of less productivity of IL-2. The IL-4 production from splenocytes of SKG mice was higher, while interferon-gamma production was lower than those of BALB/c mice. An injection of zymosan A reduced the IL-4 production only in SKG mice. CONCLUSIONS: SKG mice do not develop arthritis under the SPF condition possibly because of a low proliferative activity of T cells and Th2-predominance.

Animals↗