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Biomedical subjects

T Kubota

Publications and source records attributed to T Kubota.

At least 55 records · Page 3Linked to original sources
PubMed2002

Radio-guided sentinel node detection for gastric cancer.

BACKGROUND: Radio-guided detection of sentinel nodes (SNs) has been used to predict regional metastases in patients with malignant melanoma and breast cancer. However, the validity of the SN hypothesis is still controversial for gastrointestinal cancers including gastric cancer. The aim of this study was to test the feasibility and accuracy of radio-guided mapping of SNs for gastric cancer. METHODS: Some 145 consecutive patients with gastric cancer diagnosed as T1 or T2 and evaluated clinically as N0 were enrolled. Endoscopic injection of technetium-99m-radiolabelled tin colloid was performed before operation and radioactive SNs were identified with a gamma probe. Standard radical gastrectomy with lymphadenectomy was performed in all patients and all resected nodes were evaluated by routine histopathological examination. RESULTS: Using radio-guided methods, SNs were detected in 138 (95.2 per cent) of 145 patients. The SN was positive in 22 of 24 patients with lymph node metastasis. The incidence of metastasis in the SNs (7.8 per cent) was significantly higher than that in the non-SNs (0.3 per cent) (P < 0.01). The diagnostic accuracy according to SN status was 98.6 per cent (136 of 138). CONCLUSION: Radio-guided SN mapping is an accurate diagnostic procedure for detecting lymph node metastasis in patients with early-stage gastric cancer.

Chi-Square Distribution↗
PubMed2002

Effects of whole deletion of CYP2A6 on nicotine metabolism in humans.

We investigated the effects of CYP2A6 genotypes on nicotine metabolism, focused from nicotine to cotinine and its additional 3'-hydroxylating resulted in trans-3'-hydroxycotinine formation. In the subjects genotyped by PCR-RFLP method, one cigarette smoking experiment was performed and urine samples were collected for 24 h. In all subjects who smoked, we detected nicotine, cotinine and trans-3'-hydroxycotinine in urine by GC-MS analysis. In whole deletion of CYP2A6, urinary excretion amounts of cotinine and trans-3'-hydroxycotinine were significantly smaller than those in the wild-type of CYP2A6*1. A lack of CYP2A6 reduces the formation of cotinine and trans-3'-hydroxycotinine, but not entirely reduces the trans-3'-hydroxycotinine formation. Unknown cotinine 3'-hydroxylating activity except CYP2A6 are suspected in humans.

Aryl Hydrocarbon Hydroxylases↗
PubMed2002

Membrane potential and bicarbonate secretion in isolated interlobular ducts from guinea-pig pancreas.

The interlobular duct cells of the guinea-pig pancreas secrete HCO(3)(-) across their luminal membrane into a HCO(3)(-)-rich (125 mM) luminal fluid against a sixfold concentration gradient. Since HCO(3)(-) transport cannot be achieved by luminal Cl-/HCO(3)(-) exchange under these conditions, we have investigated the possibility that it is mediated by an anion conductance. To determine whether the electrochemical potential gradient across the luminal membrane would favor HCO(3)(-) efflux, we have measured the intracellular potential (V(m)) in microperfused, interlobular duct segments under various physiological conditions. When the lumen was perfused with a 124 mM Cl- -25 mM HCO(3)(-) solution, a condition similar to the basal state, the resting potential was approximately -60 mV. Stimulation with dbcAMP or secretin caused a transient hyperpolarization (approximately 5 mV) due to activation of electrogenic Na+-HCO(3)(-) cotransport at the basolateral membrane. This was followed by depolarization to a steady-state value of approximately -50 mV as a result of anion efflux across the luminal membrane. Raising the luminal HCO(3)(-) concentration to 125 mM caused a hyperpolarization (approximately 10 mV) in both stimulated and unstimulated ducts. These results can be explained by a model in which the depolarizing effect of Cl- efflux across the luminal membrane is minimized by the depletion of intracellular Cl- and offset by the hyperpolarizing effects of Na+-HCO(3)(-) cotransport at the basolateral membrane. The net effect is a luminally directed electrochemical potential gradient for HCO(3)(-) that is sustained during maximal stimulation. Our calculations indicate that the electrodiffusive efflux of HCO(3)(-) to the lumen via CFTR, driven by this gradient, would be sufficient to fully account for the observed secretory flux of HCO(3)(-).

Animals↗
PubMed2002

Utility of follow-up studies using meta-[123 I]iodobenzylguanidine scintigraphy for detecting recurrent neuroblastoma.

Neuroblastomas sometimes recur after the initial disappearance of the tumour. We evaluated the utility of meta-[123I]iodobenzylguanidine (123I-MIBG) scintigraphy for the detection of recurrent neuroblastomas by comparing with the measurement of biochemical markers and clinical findings. Forty patients who had received treatment for neuroblastomas were included in the study. After the disappearance of the initial tumours, periodic measurements of urinary vanillyl mandelic acid, homovanillic acid and serum neuron specific enolase values, and an 123I-MIBG scintigraphy were performed. Whenever an abnormal finding was observed, other appropriate examinations and/or follow-up examinations were performed to elucidate the true state of the patient. Eleven recurrent episodes in eight patients were observed. Most of them occurred in the bone marrow or bone. Corresponding symptoms were observed in only two episodes; the other episodes were asymptomatic, and discovered by the periodic examinations. 123I-MIBG scintigrams visualized the recurrent tumours in 10 (91%) episodes. Elevated tumour markers were observed in only three episodes. 123I-MIBG scintigrams visualized most of the recurrent tumours, unless they were accompanied by any symptoms or elevations in biochemical tumour markers. Periodic examinations with 123I-MIBG scintigraphy appears to be a useful technique for the detection of the recurrences.

3-Iodobenzylguanidine↗
PubMed2002

Relationship between cognitive function and regional cerebral blood flow in Alzheimer's disease.

The Mini-Mental State examination (MMSE) is frequently used to assess the cognitive function of neurological patients. The purpose of this study was to investigate associations between regional cerebral blood flow (rCBF) and MMSE scores in Alzheimer's disease (AD) and localization of cognitive functions. Fifty-nine patients with probable AD (21 males and 38 females; mean age 74 years) and 12 normal volunteers (five males and seven females; mean age 73 years) were studied. CBF was measured by SPECT using the N-isopropyl-p-[(123)I]iodoamphetamine autoradiography method. The CBF images were reconstructed in parallel with the orbitomeatal line and parallel to the long axis of the temporal cortex. Regions of interest were set in the cerebral and cerebellar cortex. Multivariate analysis was performed by the step-wise method, using each section of the MMSE as the dependent variable and the rCBF ratio as the independent variable. The decline in rCBF in the parietal cortex and hippocampus reflected disorientation, and the most significant cortex affecting scores on each section of the MMSE were found to be the anterior temporal cortex for registration, the frontal cortex for attention and calculation, the medial temporal cortex for recall, and the posterior temporal cortex for language.

Aged↗
PubMed2002

The proportion of cells with functional X disomy is associated with the severity of mental retardation in mosaic ring X Turner syndrome females.

Turner syndrome females (45,X) do not have mental retardation (MR), whereas some mosaic ring X Turner syndrome females, with 45,X/46,X,r(X), have severe MR. The MR is believed to be caused by a failure of X chromosome inactivation (XCI) of the small ring X chromosome, which leads to functional X disomy (FXD), To explore this hypothesis, we examined the proportion of FXD cells in the peripheral blood of four ring X Turner syndrome females with various levels of MR, using two newly developed XCI assays based on DNA methylation of X-linked genes. As a result, the two patients with extremely severe MR showed complete FXD patterns, whereas the remaining two patients with relatively milder MR showed partial FXD patterns. These results indicate that the proportion of FXD cells may be associated with the severity of MR in mosaic ring X Turner syndrome females, although this association should be confirmed by examining brain cells during development. One of the cases with severe MR and a complete FXD pattern neither lacked the XIST gene nor had uniparental X isodisomy, and we discuss the mechanism of the failure of XCI in this case.

Child↗
PubMed2002

[Delayed hydrothorax induced by a pericutaneous central venous catheter; report of a case].

We report herein a case of 53-year-old woman who suffered a hydrothorax induced by a central venous catheter which had been placed to facilitate total parenteral nutrition. The central venous catheter was inserted into the superior vena cava through the right subclavian vein. Chest X-ray film after insertion revealed proper position of the tip. She suddenly developed dyspnea and tachycardia due to right-sided hydrothorax 21 days after the insertion of the catheter. Chest X-ray showed massive pleural effusion in the right thorax, and the catheter tip inadvertently turned upward. The continuous mechanical force of the catheter tip against the SVC wall was considered to be the cause of this life-threatening delayed hydrothorax.

Catheterization, Central Venous↗
PubMed2002

The proximal form of mural thrombus in aortoiliac occlusive disease using computed tomography.

BACKGROUND: It is important to know the nature of proximal thrombus in patients with aortoiliac occlusive disease (AIOD) when juxtarenal aortic clamping is scheduled. This study was aimed to evaluate the shape and nature of thrombi at several sites of the abdominal aorta in patients with AIOD using enhanced computed tomography (CT). Final judgment was made according to the operative findings. METHODS: Between the years 1999 and 2001, 22 patients, who underwent aortobifemoral bypass, were enrolled. The shape and nature of their thrombi were examined at 4 points (superior mesenteric, suprarenal, juxtarenal and infrarenal arteries at the level of the 2 cm before the renal artery) and 88 slices of CT were examined retrospectively. RESULTS: There was mural thrombus in 31 slices, which could be classified into 4 shapes (crescent-shaped: 10 cases; magatama: 2; wavy: 12; circular: 6). The wavy and circular shaped thrombi were found to be atheromatous. Nine cases (40.9%) on operative findings were atheroma (wavy: 4; circular shaped: 5). The crescent shape might correspond to fibrin thrombus. Atheromatous thrombus clamping near the renal artery was thought to cause microthromboembolism to surrounding organs. CONCLUSIONS: It is recommended that the more proximal aorta or splanchnic arteries should be temporarily clamped during proximal procedures in patients with wavy or circular shaped thrombi at the juxtarenal aorta to prevent kidney or bowel infarction.

Aged↗
PubMed2001

Duplication of 15q11.2-q14, including the P gene, in a woman with generalized skin hyperpigmentation.

We describe a woman with 15q11.2-q14 duplication who had clinical manifestations of proximal 15q trisomy and hyperpigmentation. Within this region, the P gene, located at chromosome segment 15q11.2-q12, is associated with oculocutaneous albinism type II (OCA2) and with hypopigmentation in the Prader-Willi and Angelman chromosome 15q deletion syndromes. We therefore hypothesized that in this woman skin hyperpigmentation might result from a duplication of the P gene. We carried out chromosomal and interphase fluorescence in situ hybridization (I-FISH) analyses, and determined that the P gene is duplicated in this woman. Our findings demonstrate that trisomy of the P gene can be associated with skin hyperpigmentation.

Carrier Proteins↗
PubMed2001

DNA mediated immunization with encoding the nucleoprotein gene of porcine transmissible gastroenteritis virus.

The immune response to a naked plasmid DNA encoding the nucleoprotein (N protein) of porcine transmissible gastroenteritis virus (TGEV) was investigated in this study. A complementary DNA of the entire N gene was amplified by RT-PCR, and inserted into a mammalian expression vector (pcDNA3.1) to construct a recombinant plasmid (pcDNA/N). To evaluate the immunogenicity of the construct, BALB/c mice were intramuscularly immunized with different doses (50, 100 and 200 microg/mouse) of pcDNA/N twice at a 5-week interval. An optimal antibody response was achieved with 100 microg of pcDNA/N. The response lasted at least 11 weeks after primary immunization. By western blotting analysis, the antibodies specifically recognized a 47 kDa protein corresponding to the viral N protein, but they did not reveal neutralizing activity against infectious TGEV in vitro. Immunoglobulin G2a was predominant among these antibodies, which was indicative of Th1 type cell activation in pcDNA/N immunized mice. Moreover, spleen cells from these mice showed stronger immune responses than those from live vaccine or parental vector immunized mice. These results suggest that the construct can elicit both humoral and cell-mediated immune (CMI) responses against TGEV N protein in mice.

Animals↗
PubMed2001

DnaA protein Lys-415 is close to the ATP-binding site: ATP-pyridoxal affinity labeling.

Binding of ATP, but not of ADP, activates Escherichia coli DnaA protein for replicational initiation of the chromosome. To elucidate this switching mechanism, we used the affinity-labeling agent ATP-pyridoxal, which forms a covalent bond with the Lys residue located at or near the gamma-phosphate of ATP. ATP-pyridoxal inhibited the ATP binding for DnaA protein, with a competitive mode. Binding stoichiometry was 0.28 ATP-pyridoxal/DnaA molecule, a value consistent with that of ATP. Thus, ATP-pyridoxal was a potent antagonist for the DnaA ATP-binding site. The labeled DnaA protein was inactive for minichromosome replication in vitro, suggesting that conformation of the region is important for DnaA activity. Isolation of the labeled, tryptic fragment and the Edman degradation revealed that ATP-pyridoxal modified Lys-415. Thus, this residue is likely close to the bound ATP. Since Lys-415 is located in the DNA-binding domain, these findings imply internal interaction between the domains for ATP binding and DNA binding.

Adenosine Triphosphate↗
PubMed2001

Cellular localization of metabotropic glutamate receptors mGluR1, 2/3, 5 and 7 in the main and accessory olfactory bulb of the rat.

The cellular localization of metabotropic glutamate receptors (mGluRs) (mGluR1alpha, 2/3, 5a and 7) in the main and accessory olfactory bulb (MOB and AOB) of adult rats was compared by using affinity purified polyclonal antibodies directed to their C-termini. mGluR1alpha and mGluR5a immunoreactivities were located in comparable structures of the MOB and AOB with different levels of intensity. mGluR5a reactivity was high in the AOB. mGluR2/3 showed a different pattern of expression in the MOB compared to that observed in the AOB; the periglomerular region of the MOB was strongly stained, but in the AOB it was the mitral/tufted cell layer that was intense. The mitral cell bodies in the MOB were strongly immunoreactive for mGluR7. These differences in the distribution of mGluRs in the MOB and AOB may reflect differences in synaptic transmission and sensitivity to neuromodulation in the two systems.

Amino Acid Sequence↗
PubMed2001

Contribution of enzymic alpha, gamma-elimination reaction in detoxification pathway of selenomethionine in mouse liver.

The objective of this study was to clarify the detoxification pathways of selenomethionine (SeMet) in mouse liver. It has been postulated that SeMet may be metabolized to selenocysteine (SeCyH) via a pathway similar to methionine (Met). CySeH may be decomposed to H(2)Se, which is consequently methylated to CH(3)SeH, (CH(3))(2)Se, and (CH(3))(3)Se(+). In this study, we estimated that the median lethal single oral dose (LD(50)) was 67.0 mg/kg. We also found that (CH(3))(3)Se(+) was quickly produced in mouse liver after single oral administration of SeMet. This result suggested the existence of a quick alpha,gamma-elimination pathway. We measured the amounts of alpha-ketobutyrate, NH(3), and CH(3)SeH produced by enzymic alpha,gamma-elimination reaction of SeMet in the liver of periodate-oxidized adenosine (PAD) or D,L-propargylglycine (PPG)-treated mice in order to verify the existence of alpha,gamma-elimination enzyme. PAD is an inhibitor of S-adenosylhomocysteinase (EC 3.3.1.1), which is necessary for conversion of SeMet to SeCyH. PPG is an effective inhibitor of the pyridoxal 5'-phosphate (PLP)-containing enzyme bacterial L-methionine gamma-lyase (EC 4.4.1.11) contributing to the alpha,gamma-elimination reaction of SeMet and cystathionine gamma-lyase (EC 4.4.1.1) relating to conversion of SeMet to SeCyH. When SeMet was incubated with the S9 fraction from liver of PAD-treated mice, the formation of alpha-ketobutyrate was much the same as that from nontreated mouse liver. However, the amount of alpha-ketobutyrate formed significantly decreased in the reaction of SeMet with S9 fraction from the liver of PPG-treated mice. In an in vivo experiment using mice treated with PAD before a toxic dosage of SeMet, the amount of SeMet in the liver decreased and the amount of acid-volatile Se derived from CH(3)SeH increased gradually. This phenomenon was not observed in the PPG-pretreated group. Furthermore, the protein fraction that had the alpha,gamma-elimination enzyme activity was found in mouse liver cytosol by gel chromatographic technique. The results of this study indicated that SeMet was directly metabolized to CH(3)SeH by an alpha,gamma-elimination enzyme analogous to bacterial L-methionine gamma-lyase, in addition to the generally acceptable pathway via SeCyH.

Ammonia↗
PubMed2001

Tumor necrosis factor receptor fragment attenuates interferon-gamma-induced non-REM sleep in rabbits.

Although the somnogenic actions of interferon-alpha (IFNalpha) and IFNbeta have been reported, the sleep effects of IFNgamma remained unknown. Thus, we investigated the effects of intracerebroventricular injection of human IFNgamma on sleep in rabbits. IFNgamma dose-dependently increased nonrapid eye movement sleep (NREMS), electroencephalographic slow wave activity and brain temperature (Tbr). These effects were markedly attenuated after the heat treatment of IFNgamma. IFNgamma suppressed rapid eye movement sleep if given during the light period, but not if given at dark onset. Although a tumor necrosis factor receptor fragment did not affect any sleep parameters when given at dark onset, it significantly attenuated IFNgamma-induced NREMS and Tbr. These data suggest that IFNgamma may be involved in the sleep responses during infection. Further, IFNgamma may have a synergistic interaction with intrinsic TNFalpha in the brain.

Amino Acid Sequence↗
PubMed2001

Effect of allylic CH(3-n)F(n) groups (n = 1-3) on pi-facial diastereoselection.

[structure: see text]. Michael addition of various enolates toward gamma-CH(3-n)F(n)-alpha,beta-unsaturated ketones (n = 1-3) was proven to smoothly furnish the 1,4-adducts with high si face selectivities which monotonously decreased by reduction in the number of fluorines. Although the Felkin-Anh model correctly anticipates the present stereochemical outcome only with E-acceptors, the hyperconjugative stabilization of transition states by electron donation from the allylic substituents (the Cieplak rule) successfully explains the pi-facial preference of both acceptors at least in a qualitative level.

Journal Article↗
PubMed2001

Herpes simplex virus type 1 suppresses the interferon signaling pathway by inhibiting phosphorylation of STATs and janus kinases during an early infection stage.

We examined the influence on the interferon (IFN) signaling pathway of infection with herpes simplex virus type 1 (HSV-1) strain VR3. Data from reporter gene assays showed that expression of both type I and type II IFN-inducible genes was dramatically suppressed during the early stage of HSV-1 infection (2 to 3 h postinfection). During these periods, phosphorylation levels of janus kinases (JAKs) and STATs did not increase after treatment of HSV-1-infected FL cells with IFN-alpha or IFN-gamma, although cellular protein levels of the JAKs and the STATs were not significantly changed. In contrast, the inhibitory effect of HSV-1 on phosphorylation of STAT1 was not observed in U937 cells, which show resistance to steady-state accumulation of RNA for HSV-1 immediate-early genes. The phosphorylation of STAT1 in FL cells was not inhibited by infection with a UV-inactivated virus. These results indicate that viral gene expression or viral protein production is necessary for the inhibition of phosphorylation by HSV-1.

DNA-Binding Proteins↗
PubMed2001

Diastereoselective inter- and intramolecular pinacol coupling of aldehydes promoted by monomeric titanocene(II) complex Cp(2)TiPh.

A monomeric titanocene(III) derivative, Cp(2)TiPh, effectively promoted the pinacol coupling of both an aromatic aldehyde, benzaldehyde, and an aliphatic aldehyde, 3-phenylpropionaldehyde. The same reactive complex was successfully generated by a catalytic amount of a precursor, Cp(2)Ti(Ph)Cl, and its stoichiometric amount of Zn. The Cp(2)TiPh-catalyzed pinacol coupling of benzaldehyde derivatives and aliphatic aldehydes afforded the corresponding 1,2-diols in high yields with moderate to good threo-selectivity. On the other hand, Cp(2)TiPh-catalyzed pinacol cyclization of dials gave cyclic 1,2-diols with excellent diastereoselectivity. The extension of this protocol to chiral dials demonstrated that the phenyltitanium complex catalytically transmitted an axial chirality or a central chirality of the starting dials to the central chirality of the resultant 1,2-diols.

Journal Article↗