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Y Yamada

Publications and source records attributed to Y Yamada.

At least 181 records · Page 10Linked to original sources
PubMed2001

Bcl-X expression in esophageal squamous cell carcinoma: association with tumor progression and prognosis.

BACKGROUND AND OBJECTIVES: Bcl-2 family proteins are regulators of programmed cell death and important in the development and progression of human various tumors. The role of these proteins in the development, progression and differentiation of esophageal squamous cell carcinoma (ESCC) is unclear. METHODS: We investigated the expression of Bcl-2, Bcl-X, and Bax using immunohistochemistry in 86 ESCCs, and scored the expression by the weighted score. RESULTS: Bcl-2 expression related to pT category (P=0.043) and histological grade (P = 0.001). Bcl-X expression related to pT category (P = 0.003), pN category (P = 0.041) and the number of positive nodes (P = 0.036), and had a tendency to relate to histological grade (P = 0.086). Bax expression had a tendency to relate to pN category (P = 0.081). The inverse relationship between Bcl-2 and Bcl-X expression was detected (P = 0.001), while the positive one between Bcl-X and Bax expression was detected (P = 0.014). Patients with low Bcl-X weighted score had a significantly longer survival compared with those with high Bcl-X weighted score. Multivariate analysis revealed Bcl-X expression as the independent prognostic factors (P = 0.022). CONCLUSION: These results imply that Bcl-2 family proteins, especially Bcl-X, may contribute to the progression in ESCC.

Adult↗
PubMed2001

Laminin synthesis and the adhesion characteristics of immortalized human corneal epithelial cells to laminin isoforms.

We have studied the synthesis of laminins (Ln) and determined the specific integrins mediating the adhesion of immortalized human corneal epithelial cells to mouse Ln-1, and human Lns-5 and -10. Immunofluorescence microscopy of the cells demonstrated integrin alpha(2), alpha(3), alpha(6), beta(1)and beta(4)subunits, integrins alpha(6)and beta(4)being found in a typical 'leopard-skin' like manner. Immunoprecipitation studies showed that the cells produced alpha 3, beta 3 and gamma 2 chains of Ln-5, but not Lns-1 or -10. In culture Ln-5 was found as small plaques beneath the adhering cells within 1 hr, while in 4 hr widely spread Ln-5 plaques were observed in colocalization with beta(4)integrin subunit. By using a quantitative cell adhesion assay and function-blocking monoclonal antibodies we showed that integrin beta(1)subunit plays a role in mediating corneal epithelial cell adhesion to mouse Ln-1. However, none of the available function-blocking antibodies to integrin alpha-subunits inhibited the adhesion. Integrin alpha(3)beta(1)complex mediated the adhesion of corneal epithelial cells to human Lns-5 and -10. Integrin complex alpha(3)beta(1), as well as laminin alpha(3)chain, was also shown to mediate cell adhesion to newly produced endogenous Ln-5. The present results show that integrin alpha(3)beta(1)complex mediates the adhesion of corneal epithelial cells to Lns-5 and -10, while a yet unknown integrin alpha subunit appears to play a role in the adhesion to Ln-1. The results also show that among corneal basement membrane laminins, Ln-5 is synthetized by epithelial cells while Ln-10 may be a product of keratocytes.

Animals↗
PubMed2001

Alternation of inwardly rectifying background K+ channel during development of rat fetal cardiomyocytes.

The resting membrane potential of rat ventricular myocytes dramatically hyperpolarizes in the late phase of the fetal period. In order to investigate the mechanisms of this hyperpolarization, we examined the electrophysiological properties and molecular structure of the inwardly rectifying background K+ channels of rat fetal ventricular myocytes. In a patch-clamp experiment the whole-cell current of the inwardly rectifying background K+ channel increased 12-fold from between 12 and 18 days after impregnation. In the single channel recording, the large-conductance (35 pS) channels were mainly observed in the 18-day fetal ventricular myocytes. In the 12-day cells, the large-conductance channel was not observed although the low-conductance channels (11 and 16 pS) were infrequently observed. These data of single channel recordings suggested that channel proteins conducting the inwardly rectifying background K+ current were altered during the fetal development. Therefore, we compared the expression of Kir 2.1 mRNA and Kir 2.2 mRNA between 12 days and 18 days using the RT-PCR method, in order to investigate the possible molecular regulation which contributes to the electrophysiological changes. During the fetal period, the expression of Kir 2.2 mRNA increased tremendously (17 times), whereas the increase in the expression of Kir 2.1 mRNA (two times) was not so great. These results show that hyperpolarization in the late fetal period seems to be mainly due to the dramatic increase in expression of Kir 2.2 mRNA rather than expression of Kir 2.1 mRNA.

Action Potentials↗
PubMed2001

Successful treatment with a chimeric anti-CD20 monoclonal antibody (IDEC-C2B8, rituximab) for a patient with relapsed mantle cell lymphoma who developed a human anti-chimeric antibody.

Mantle cell lymphoma (MCL) has a poor prognosis without cure; the median overall survival ranges only from 3 to 4 years irrespective of conventional therapeutic regimens. IDEC-C2B8 (rituximab), a chimeric monoclonal antibody against the B-cell-specific antigen CD20, induces an evaluable clinical response in patients with MCL with mild toxicities. However, the single agent rituximab cannot cure MCL. Due to its low immunogenicity, an antibody against IDEC-C2B8 (human antichimeric antibody [HACA]) has rarely been produced in vivo. We report a patient with relapsed MCL who was successfully treated with IDEC-C2B8 for over a year although she developed HACA 6 months after the initial administration of IDEC-C2B8 in the phase II clinical trial conducted by Zenyaku Kogyo Co. Ltd. We followed the pharmacokinetics of IDEC-C2B8, the serum HACA titer, and the number of B lymphocytes in the peripheral blood in relation to clinical response. The HACA became undetectable soon after subsequent administrations of IDEC-C2B8. When the serum level of IDEC-C2B8 was kept elevated, clinical responses were apparently observed and HACA disappeared during this response period. There were no significant clinical toxicities related to the appearance of HACA. The present findings suggested that IDEC-C2B8 is effective and safe even in patients who have developed HACA.

Aged↗
PubMed2001

Association of the C-509-->T polymorphism, alone of in combination with the T869-->C polymorphism, of the transforming growth factor-beta1 gene with bone mineral density and genetic susceptibility to osteoporosis in Japanese women.

Transforming growth factor-beta1 is an important local regulator of bone metabolism, acting downstream of estrogen and cooperatively with vitamin D. The possible association of a C 509-->T polymorphism in the promoter region of the transforming growth factor-beta1 gene, alone or in combination with a T869-->C (Leu10-->Pro) polymorphism, with bone mineral density and genetic susceptibility to osteoporosis was investigated in 625 postmenopausal Japanese women. The frequencies of the CC, CT, and TT genotypes of the C-509-->T polymorphism in the study population were 24%, 49%, and 27%, respectively. A significant association of C-509-->T genotype with bone mineral density was detected: lumbar spine (L2-L4) and total body bone mineral density values were 7% and 5% lower, respectively, in individuals with the TT genotype than in those with the CT or CC genotype. The serum concentration of transforming growth factor-beta1 did not vary with C-509-->T genotype. Multivariable logistic regression analysis, with adjustment for age, height, body weight, time since menopause, smoking status, body fat mass, and lean mass, revealed a significantly higher frequency of the TT genotype of the C-509-->T polymorphism in 286 individuals with osteoporosis than in 170 normal controls. Analysis of combined C-509-->T and T869-->C genotypes showed that L2-L4 bone mineral density decreases and the prevalence of osteoporosis increases with the number of T alleles. These results suggest that the C-509-->T polymorphism, alone or in combination with the T869-->C polymorphism, of the transforming growth factor-beta1 gene is a genetic determinant of bone mass, and that the number of T alleles in the combined genotype is a risk factor for the genetic susceptibility to osteoporosis in postmenopausal Japanese women.

Aged↗
PubMed2001

Commencing, continuing and stopping brisk walking: effects on bone mineral density, quantitative ultrasound of bone and markers of bone metabolism in postmenopausal women.

Regular walking is associated with reduced risk of fracture and, in our recent randomized trial, reduced calcaneal bone loss relative to controls. The present follow-up study compared the effects on dual-energy X-ray absorptiometry, ultrasound and biochemical indices of bone density and metabolism of (i) taking up (ii) continuing with and (iii) ceasing brisk walking for exercise. Subjects were 68 postmenopausal women aged 60-70 years. Twenty previously sedentary women remained sedentary (Sed/Sed) whilst 17 took up brisk walking (Sed/Walk). Fifteen women who had been walking regularly for 1 year returned to their former sedentary lifestyle (Walk/Sed), whilst 16 continued brisk walking over a second year (Walk/Walk). Bone mineral density (BMD), broadband ultrasonic attenuation (BUA), and biochemical markers of bone formation (serum osteocalcin, C-terminal propeptide of type I collagen and bone alkaline phosphatase) and resorption (urinary deoxypyridinoline) were assessed at baseline and 12 months. Women in the Sed/Walk and Walk/Walk groups completed a mean (SEM) of 16.9 (0.7) and 20.8 (1.2) min of brisk walking per day, respectively. Changes in BMD did not differ significantly between groups. Calcaneal BMD decreased significantly in Walk/Sed women [by 2.7 (1.4)%; p = 0.01] whilst changes in other groups were not significant. Calcaneal BUA increased significantly (p = 0.02) in Sed/Walk women [by 7.4 (3.3)%] relative to other groups. Urinary deoxypyridinoline increased over the year in the Sed/Sed group but there were no significant changes in biochemical markers in other groups. Women taking up brisk walking for exercise showed no change in BMD but a significant increase in calcaneal BUA. There was no significant effect on BMD or BUA of continuing brisk walking but calcaneal BMD declined on ceasing brisk walking. Bone resorption increased in sedentary women but not exercisers, suggesting the effect on exercise on bone in postmenopausal women could be through amelioration of this increased turnover.

Absorptiometry, Photon↗
PubMed2001

Decrease in the Ca2+-activated K+ current of pulmonary arterial smooth muscle in pulmonary hypertension rats.

Pulmonary hypertension exhibits acute elevation of vascular tone and hyperreactivity of pulmonary vasculature, which are closely related to patient mortality. In the present study, we investigated the characteristics of membrane currents of isolated pulmonary artery smooth muscle cells taken from rats with monocrotaline-induced pulmonary hypertension. Male Wistar rats were given a single subcutaneous injection of monocrotaline or saline, and then sacrificed between 18 to 21 days after the injection. The membrane currents in the smooth muscle cells from both groups of rats were compared using the whole-cell patch clamp technique. With 0.1 mM EGTA in the pipette, the densities of outward currents in monocrotaline-injected rats were smaller than those in control rats. When EGTA in patch pipettes was increased to 10 mM, the densities of the outward currents in monocrotaline-injected rats were equal to those of control rats. The Ca2+-activated K+ channel blockers (TEA, iberiotoxin) and nisoldipine were less effective on the outward currents of monocrotaline-injected rats. In the current clamp mode, a depolarization of membrane potential induced by 4-aminopyridine was greater in monocrotaline-injected rats than in control rats because of the reduced activity of the Ca2+-activated K+ channels. The Ca2+-activated K+ channels were decreased in pulmonary hypertension. The reduced activity of the currents may be related to the vascular hyperreactivity in pulmonary hypertension.

Analysis of Variance↗
PubMed2001

Expression of paraoxonase isoform did not confer protection from acute sarin poisoning in the Tokyo subway terrorist attack.

We previously reported the polymorphism of the high density lipoprotein-associated enzyme paraoxonase (PON1), in the 10 sarin poisoning victims in the Tokyo subway terrorist attack. Arg192 PON1, which has low sarin hydrolysing activity, was found to be more common in the Japanese population than in people of other races. However, from our analyses seven of the victims expressed the PON1 phenotype with high sarin hydrolysing activity and three with low sarin hydrolysing activity. These results indicate that the main factor contributing to the tragedy of the Tokyo subway terrorist attack was the high toxicity of sarin rather than the race-dependent genetic difference in the Arg192 PON1 polymorphism.

Aged↗
PubMed2001

Self-reported recovery time of daily activity after bone marrow harvesting from healthy donors.

PURPOSE: The study was planned to describe and compare the resumption of daily activity after bone marrow harvesting (BMH) under general anesthesia with different anesthetic agents, isoflurane, sevoflurane and propofol. METHODS: Sixty-five adult healthy allogenic donors (26 women, 39 men; 37.0 +/- 9.5 years of age; ASA class I or II) were studied. BMH was performed under general anesthesia with isoflurane, sevoflurane, or propofol as the main anesthetic agent. On day 1, donors were asked how soon they could resume five daily activities: talking, walking, drinking, eating, and reading. RESULTS: Although there was considerable variation in resumption time within and among these five activities, 77% of donors resumed all of these basic daily activities within 12 h after BMH. Donors who received propofol resumed talking significantly faster than those who received sevoflurane or isoflurane, but the choice of main anesthetic agent did not affect the time of resumption of other activities. Lower preoperative hemoglobin concentration and greater decline of hemoglobin concentration on day 1 were significantly associated with slower resumption of walking and reading. CONCLUSION: Although the choice of main anesthetic agent and anemia affected postoperative recovery, 77% of donors could resume these five daily activities within 12 h.

Journal Article↗
PubMed2001

Association of a G994 --> T (Val279 --> Phe) polymorphism of the plasma platelet-activating factor acetylhydrolase gene with myocardial damage in Japanese patients with nonfamilial hypertrophic cardiomyopathy.

Plasma platelet-activating factor acetylhydrolase (PAF-AH) acts as a key defense against oxidative stress by hydrolyzing PAF and oxidized phospholipids. Deficiency of the activity of this enzyme may thus potentially result in predisposition to myocardial damage. The possible role of the G994 (V allele) --> T (F allele) polymorphism of the PAF-AH gene in modulating cardiac function was investigated in 142 Japanese subjects with nonfamilial hypertrophic cardiomyopathy (HCM). Logistic regression analysis adjusted for age, sex, height, and body weight revealed that the frequency of the F allele was significantly higher in HCM patients than in 284 healthy controls. Echocardiographic examination revealed that left ventricular (LV) end-diastolic and end-systolic dimensions were significantly greater in HCM patients with the FF genotype than in those with the VV genotype. Cardiac catheterization revealed that LV end-diastolic pressure was significantly higher, whereas the LV ejection fraction was significantly smaller, for HCM patients with the F allele than for those with the VV genotype. Interstitial fibrosis was significantly more severe in HCM subjects with the FF genotype than in those with the VV genotype. These results suggest that the G994 --> T (Val279 --> Phe) polymorphism in the plasma PAF-AH gene may exacerbate cardiac damage in Japanese individuals with nonfamilial HCM, although this polymorphism is unlikely to be a causative factor for this condition.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed2001

Emergence of cephem- and aztreonam-high-resistant Neisseria gonorrhoeae that does not produce beta-lactamase.

Regarding Neisseria gonorrhoeae, the National Committee for Clinical Laboratory Standards (NCCLS) has not defined the breakpoint minimum inhibitory concentration (MIC) for expanded spectrum cephems such as cefpodoxime and ceftizoxime, because of the absence of resistant strains to these antibiotics. To date, in gonococcal urethritis, after treatment with third generation cephems and aztreonam, clinical failures caused by resistant N. gonorrhoeae strains have not been reported. However, we experienced two clinical failures in patients with gonococcal urethritis treated with cefdinir and aztreonam. N. gonorrhoeae isolates from these two patients showed high-level MICs to these agents. The MIC of cefdinir was 1 microg/ml for both strains and that of aztreonam was 8 microg/ml for both strains, while the MICs of other beta-lactams were also higher than the NCCLS value, except for ceftriaxone, for which the MIC was 0.125 microg/ml for both strains. Moreover, the MICs of fluoroquinolones, tetracyclines, and erythromycin against these two isolates were higher than the NCCLS susceptibility value. These isolates were susceptible to spectinomycin. In N. gonorrhoeae, the emergence of these beta-lactam-resistant isolates is of serious concern. However, a more serious problem is that these isolates were already resistant to non-beta-lactam antimicrobials. In Japan, ceftriaxone has not been permitted for clinical use against gonococcal infections. Therefore, in Japan, patients with gonococcal urethritis caused by these resistant N. gonorrhoeae strains should be treated with cefodizime or spectinomycin.

Adult↗
PubMed2001

Failure of ureteric bud invasion: a new model of renal agenesis in mice.

FUBI (failure of ureteric bud invasion) is a highly inbred strain of mouse with a high spontaneous incidence of uni- or bilateral renal agenesis (60%). Bilateral renal agenesis is lethal within 2 days after birth. The primary defect of FUBI is failure of the ureteric bud to penetrate into the metanephric mesenchyme at around embryonic day 11, resulting in apoptosis of metanephric cells and leading to renal agenesis on the affected side. The metanephros seemed to be normal because co-culturing of the FUBI metanephros with homologous spinal cord induced differentiation of the rudiment, but co-culturing with the homologous ureteric bud frequently did not. Genetic analysis revealed that more than two genes were involved in this malformation and we mapped one of the modifier loci, fubi1, on chromosome 2, at approximately 65 cM from the centromere. In this region, there are two possible candidate genes, Wilms' tumor 1 and formin, that play important roles in kidney development. Some of formin mutants shared a similar phenotype with FUBI; however, there was no difference in the expression of formin in embryonic kidneys between FUBI and control NFS/N mice. Studies of fubi1 congenic mice indicated that interaction of two or more loci is essential for the FUBI phenotype.

Animals↗
PubMed2001

Optical imaging reveals cation--Cl(-) cotransporter-mediated transient rapid decrease in intracellular Cl(-) concentration induced by oxygen--glucose deprivation in rat neocortical slices.

In brain slices from young (postnatal day (P) 10--15) rat somatosensory cortex, real-time neuronal intracellular Cl(-) concentration ([Cl(-)](i)) recordings were made by an optical technique measuring 6-methoxy-N-ethlquinolinium iodide (MEQ) fluorescence. Oxygen--glucose deprivation (in vitro model of ischemia) induced a long-lasting [Cl(-)](i) increase preceded by a rapid, transient [Cl(-)](i) decrease that could not be inhibited by blockers of Cl(-) pumps, Cl(-) channels, or Cl(-) antiporters, but was sensitive to cation-Cl(-) cotransporter inhibitors (bumetanide and furosemide). Use of low external Na(+) or high external K(+) revealed that the Na(+),K(+)-2Cl(-) cotransporter was inhibited by bumetanide and furosemide, whereas the K(+)-Cl(-) cotransporter was preferentially inhibited by furosemide under our experimental conditions. With a reduced inward driving force for Na(+) (reducing Na(+),K(+)-2Cl(-) cotransport), the transient [Cl(-)](i) decrease was only rarely induced by oxygen-glucose deprivation. In contrast, with a reduced outward driving force for K(+) (reducing K(+)-Cl(-) cotransport), the transient [Cl(-)](i) decrease still occurred. These results suggest that the transient [Cl(-)](i) decrease was primarily mediated by a rapid inhibition of the inwardly directed Na(+),K(+)-2Cl(-) cotransporter. Reverse transcriptase-polymerase chain reaction (RT-PCR) experiments suggested that the isoform involved is NKCC1. We hypothesize that the initial rapid Cl(-) efflux might effectively delay the irreversible Cl(-) influx that mediates neuronal injury.

Animals↗
PubMed2001

Changes in jaw reflexes by stimulation of the hypothalamus in anesthetized rabbits.

Changes in the masseteric monosynaptic reflex (MMR) and jaw-opening reflex (JOR) responses resulting from conditioning stimulation in the hypothalamus were studied in anesthetized rabbits. Stimulation of the lateral hypothalamus evoked a facilitation of the MMR and an inhibitory or facilitatory effect on the JOR. The facilitatory effect on JOR was stronger than that on the MMR. The facilitatory effective site for the JOR was in the dorsal and lateral directions as compared to the inhibitory field. The results suggest two functionally distinct regions in the lateral hypothalamus that separately project to the jaw-opening muscles.

Aggression↗
PubMed2001

Distinct effect of diazoxide on insulin secretion stimulated by protein kinase A and protein kinase C in rat pancreatic islets.

Protein kinase activation is known to stimulate glucose-induced insulin secretion in the presence of diazoxide. Diazoxide opens the ATP-sensitive K(+) channel and inhibits FAD-linked glycerophosphate dehydrogenase activity in a concentration-dependent manner. In the present study, we examined the effect of lower (100 microM) and higher (250 microM) concentrations of diazoxide on insulin release by protein kinase A (PKA) and protein kinase C (PKC) activation. Forced depolarization by a high potassium concentration, augmented the intracellular Ca(2+) concentration ([Ca(2+)](i)) similarly in the presence of both concentrations of diazoxide. Under this condition, 250 microM diazoxide inhibited insulin release enhanced by PKA activation but not that by PKC. Under a basal concentration of [Ca(2+)](i), PKC activation elicited glucose-induced insulin secretion at 100 and 250 microM diazoxide, while PKA activation did so only at 100 microM. These augmentations were completely inhibited by mannoheptulose, a glucokinase inhibitor. Glyceraldehyde, in place of glucose, enhanced insulin secretion by PKC activation under both concentrations of diazoxide. On the other hand, it did not affect PKA-stimulated insulin release under either conditions, but in the case of 100 microM, glucose augmented the insulin secretion in the presence of glyceraldehyde and db-cAMP concentration-dependently. These data suggest that insulin release stimulated by PKA and PKC activation under diazoxide is dependent on glucose metabolism, and that a signal derived from proximal steps in glycolysis may be necessary for the secretion by PKA activation.

Animals↗
PubMed2001

Expression of CC chemokine receptor 3 on human keratinocytes in vivo and in vitro--upregulation by RANTES.

CC chemokines and their ligands, CC chemokine receptors (CCRs), play an important role in the process of inflammation such as trafficking and activating inflammatory cells. CCR3 is known to be a ligand for CC chemokines such as RANTES, eotaxin and monocyte-chemotactic protein-3 (MCP-3). In this study we examined the expression of CCR3 in cultured normal human keratinocytes (KCs). CCR3 protein and mRNA expressions were detected in cultured normal KCs by flow cytometric (FACS) analysis and reverse-transcription-polymerase chain reaction (RT-PCR) analysis. FACS analysis demonstrated that CCR3 expression on KCs was significantly upregulated when the cells were cultured with RANTES, but not with eotaxin, IL-4 or interferon-gamma. RT-PCR analysis revealed that CCR3 mRNA was detectable in normal KCs. We also examined the immunoreactivity of CCR3 in normal skin and inflammatory skin lesions. CCR3 was detected weakly in epidermis of normal skin, while strong immunoreactivity for CCR3 was seen in epidermis of inflammatory skin lesions such as atopic dermatitis. These results suggest that CCR3 is constitutively expressed on KCs and is involved in inflammatory modulation. RANTES may regulate the function of KCs through CCR3.

Base Sequence↗
PubMed2001

Mössbauer study of the reaction of laser-evaporated iron atoms with nitrogen molecules in low-temperature argon matrices.

Reaction products of laser-evaporated iron atoms with nitrogen molecules were investigated using a low-temperature matrix isolation technique. The products observed in the Mössbauer spectra were FeNNN, Fe(NN), and Fe(NN)2, isolated in argon matrices. Yields of the species changed, depending on the concentration of nitrogen in the matrix. A product assigned to Fe(NN)6 was obtained in a pure nitrogen matrix. Infrared spectra and molecular orbital calculations of the products support these findings.

Journal Article↗