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Biomedical subjects

S Usui

Publications and source records attributed to S Usui.

At least 19 recordsLinked to original sources
PubMed2003

Effects of bezafibrate and pravastatin on remnant-like lipoprotein particles and lipoprotein subclasses in type 2 diabetes.

The effects of bezafibrate and pravastatin on remnant-like lipoprotein particles (RLPs) and lipoprotein subclasses were compared in type 2 diabetes. Bezafibrate (400 mg/day) and pravastatin (10 mg/day) were given to 27 Japanese diabetics in a randomized crossover design. RLP cholesterol (RLP-C) and RLP triglyceride (RLP-TG) were measured by an immunoseparation technique. LDL and HDL were separated each into three subclasses (large, medium, small) and their cholesterol (C) contents were measured by an HPLC method. RLP-C was reduced more effectively by pravastatin (bezafibrate -16.0% vs. pravastatin -40.6%, P < 0.05), whereas RLP-TG was reduced more effectively by bezafibrate (-55.2% vs. -35.0%, P < 0.05). Further, pravastatin decreased large and small LDL-C levels equally (large; -23.6%; medium; -17.2%, small; -21.0%), while bezafibrate produced a relatively larger reduction in small LDL-C (-12.1; -16.9; -21.5%). Whereas bezafibrate significantly decreased large HDL-C and increased medium and small HDL-C (-49.6; 34.1; 35.8%), pravastatin significantly increased only medium HDL-C (5.2; 9.4; 5.9%). Bezafibrate reduced RLP-C and RLP-TG more effectively in patients with high TG levels, whereas pravastatin's effect was not markedly influenced by the initial TG level. Thus measurements of RLP-C, RLP-TG, and HPLC subclasses revealed that bezafibrate and pravastatin differently influence the lipoprotein status in type 2 diabetes.

Aged↗
PubMed2002

Imidazole-induced cell death, associated with intracellular acidification, caspase-3 activation, DFF-45 cleavage, but not oligonucleosomal DNA fragmentation.

Intracellular acidification is known to be involved in the initiation phase of apoptosis. However, the necessity of intracellular acidic conditions in the execution phase of apoptosis remains unknown. In this study, we found that in HL-60 cells imidazole induces cell death, associated with intracellular acidification, caspase-3 activation and DFF-45 cleavage, but not oligonucleosomal DNA fragmentation. A caspase inhibitor prevented cell death but not intracellular acidification. When pHi was neutralized by changing from imidazole-containing medium to fresh medium, oligonucleosomal DNA fragmentation and increased caspase-3 activity was observed in the imidazole-treated HL-60 cells. Furthermore, the DNA fragmentation induced by intracellular neutralization was inhibited by caspase inhibitor treatment. These results indicate that imidazole induces caspase-dependent cell death, and suggest that maintaining pHi in the neutral range is essential for the induction of oligonucleosomal DNA fragmentation in the execution phase of apoptosis.

Apoptosis↗
PubMed2001

Aminopeptidase N regulated by zinc in human prostate participates in tumor cell invasion.

Aminopeptidase N (AP-N) degrades collagen type IV and is proposed to play a role in tumor invasion. However, the precise functions of AP-N in tumor cells and the relationship of AP-N to prostate cancer remains unclear. In our study, we examined a possible role for zinc in the regulation of AP-N enzymatic activity in relation to tumor cell invasion in human prostate. AP-N purified from human prostate was irreversibly inhibited by low concentrations of zinc (Ki = 11.2 microM) and bestatin. AP-N, which has zinc in the active center, was also inhibited by the chelating agents, EDTA, o-phenanthroline and EGTA. EDTA was shown to remove zinc from the enzyme. When the effects of zinc and bestatin on invasion of PC-3 cells were investigated in vitro using a Transwell cell-culture chamber, zinc and bestatin effectively suppressed cell invasion into Matrigel at the concentration range of 50-100 microM. These results strongly suggest that the suppression of PC-3 cell invasion by zinc is based on the inhibition of AP-N activity by zinc. We also evaluated the expression of AP-N to investigate the relationship with the progression of prostate disease in human cancerous prostate. AP-N was found to be located at the cytoplasmic membranes of prostate gland epithelial cells and to be expressed more in prostate cancer, while the expression of prostate-specific antigen (PSA), which is a useful marker for prostate cancer, was shown in normal and cancer tissues, suggesting that AP-N is potentially a good histological marker of prostate cancer. Thus, highly expressed AP-N in human cancerous prostate probably plays an important role in the invasion and metastasis of prostate cancer cells.

Amino Acid Sequence↗
PubMed2001

Induction of epithelial differentiation and DNA demethylation in hamster malignant oral keratinocyte by ornithine decarboxylase antizyme.

The hamster ornithine decarboxylase antizyme (ODC-Az) cDNA was transfected into the hamster malignant oral keratinocyte cell line, HCPC-1. Ectopic expression of ODC-Az resulted in the reversion of malignant phenotypes and alteration of DNA methylation status of CCGG sites. The phenotypes examined include ODC enzymatic activity, doubling time, morphological change, anchorage dependent growth, tumorigenicity in nude mice, induction of epithelial differentiation marker protein (involucrin), and change of cell cycle position. Comparison of CCGG DNA methylation status of the ODC-Az and control vector transfectants revealed a significant increase in demethylation of 5-methyl cytosines (m5C) of CCGG sites in the ODC-Az transfectants. Ectopic expression of ODC-Az gene in hamster malignant oral keratinocytes led to reduce ODC activity and the subsequent demethylation of 5-methyl cytosines, presumably via the ODC/ polyamines/ decarboxylated S-adenosylmethionine (dc-AdoMet) pathways. Our data suggest that ODC-Az shared the same pathway of polyamines/ dc-AdoMet/DNA methyltransferase (DNA MTase). We propose that ODC-Az mediates a novel mechanism in tumor suppression by DNA demethylation and presumably re-activation of key cellular genes silenced by DNA hypermethylation during cancer development. Oncogene (2001) 20, 24 - 33.

Agar↗
PubMed2001

Myristoleic acid, a cytotoxic component in the extract from Serenoa repens, induces apoptosis and necrosis in human prostatic LNCaP cells.

BACKGROUND: Prostatic tumors are well known to progress to hormonal therapy-resistant terminal states. At this stage, there are no chemotherapeutic agents to affect clinical outcome. An effective cell death inducer for these prostate cells may be a candidate as an attractive antitumor agent. The extracts from S. repens have been used to improve the state of prostatic diseases and we have attempted to identify the effective component from the extract. METHODS: Cell viability was examined in LNCaP cells, an in vitro model for hormonal therapy-resistant prostatic tumor. RESULTS: We found that exposure of the extract from S. repens resulted in cell death of LNCaP cells. We also identified myristoleic acid as one of the cytotoxic components in the extract. The cell death exhibited both apoptotic and necrotic nuclear morphology as determined by Hoechst 33342 staining. Cell death was also partially associated with caspase activation. CONCLUSIONS: It was demonstrated that the extract from S. repens and myristoleic acid induces mixed cell death of apoptosis and necrosis in LNCaP cells. These results suggest that the extract and myristoleic acid may develop attractive new tools for the treatment of prostate cancer.

Amino Acid Chloromethyl Ketones↗
PubMed2001

Basic fibroblast growth factor inhibits choriocapillaris atrophy in rabbit.

PURPOSE: To examine the effect of basic fibroblast growth factor on induced choriocapillaris atrophy in vivo. METHODS: Choriocapillaris atrophy was surgically induced in rabbits by a hydraulic retinal detachment followed by debridement of the retinal pigment epithelium under the detached retina. Three concentrations of basic fibroblast growth factor (0.1 microg/0.1 ml, 1 microg/0.1 ml, or 5 microg/0.1 ml) were injected into the subretinal space and into the vitreous cavity 1, 3, and 5 days after the surgery. For control, only Tris buffer was injected in the same manner. The rabbits were euthanized 7 days after the surgery. Choroidal vascular casts were made and examined by scanning electron microscopy. The choriocapillaris atrophy was quantified by computer-assisted image analysis of photographs of the choriocapillaries. The area of the choriocapillaris and number of intercapillary spaces in the choriocapillaris that corresponded to the density of the capillary network were measured. RESULTS: The average area of the choriocapillaris in the eyes treated with 1 microg/0.1 ml of basic fibroblast growth factor was significantly larger at 75.1 +/- 3.0% than that in the control eyes at 67.2 +/- 5.6% (P =.021). The average area of the choriocapillaris in the 0.1 microg/0.1 ml of basic fibroblast growth factor group was not statistically different from the control. The number of intercapillary spaces of the choriocapillaris was 132 +/- 12 in the 0.1 microg/0.1 ml of basic fibroblast growth factor group, 124 +/- 46 in the 1 microg/0.1 ml of basic fibroblast growth factor group, and 75 +/- 14 in the control group. The higher number of spaces in the treated group was statistically significant (P =.026). CONCLUSIONS: Basic fibroblast growth factor decreased the atrophy of the choriocapillaris after removal of the retinal pigment epithelium in rabbit eyes. These results suggest that basic fibroblast growth factor may play a role in the survival of the choriocapillaris in vivo.

Animals↗
PubMed2001

Upper bound of the expected training error of neural network regression for a Gaussian noise sequence.

In neural network regression problems, often referred to as additive noise models, NIC (Network Information Criterion) has been proposed as a general model selection criterion to determine the optimal network size with high generalization performance. Although NIC has been derived using asymptotic expansion, it has been pointed out that this technique cannot be applied under the assumption that a target function is in a family of assumed networks and the family is not minimal for representing the target true function, i.e. the overrealizable case, in which NIC reduces to the well-known AIC (Akaike Information Criterion) and others depending on a loss function. Because NIC is the unbiased estimator of generalization error based on training error, it is required to derive the expectations of errors for neural networks for such cases. This paper gives upper bounds of the expectations of training errors with respect to the distribution of training data, which we call the expected training error, for some types of networks under the squared error loss. In the overrealizable case, because the errors are determined by fitting properties of networks to noise components, including in data, the target set of data is taken to be a Gaussian noise sequence. For radial basis function networks and 3-layered neural networks with bell shaped activation function in the hidden layer, the expected training error is bounded above by sigma2* - 2nsigma2*logT/T, where sigma2* is the variance of noise, n is the number of basis functions or the number of hidden units and T is the number of data. Furthermore, for 3-layered neural networks with sigmoidal activation function in the hidden layer, we obtained the upper bound of sigma2* - O(log T/T) when n > 2. If the number of data is large enough, these bounds of the expected training error are smaller than sigma2* - N(n)sigma2*/T as evaluated in NIC, where N(n) is the number of all network parameters.

Analysis of Variance↗
PubMed2001

Decreases of metallothionein and aminopeptidase N in renal cancer tissues.

Good molecular markers for investigating the biochemical differences between renal cancer and surrounding tissues have not yet been developed. Sixteen kidney samples (clear cell RCC) were investigated to determine the differences in the protein components between renal cancer and surrounding tissues, using HPLC analysis. The metallothionein (MT) and zinc levels were consistently lower in renal cancer tissues compared with in surrounding tissues. The mean concentration of MT in normal tissues surrounding renal tumors was about 15 times higher than that in cancer tissues. An immunohistochemical study confirmed that the expression of MT in renal cancer tissues was lower than that in adjacent normal tissues. The activities of aminopeptidases (APs) were significantly decreased in renal cancer tissues compared with in adjacent normal tissues. An immunohistochemical study and Western blot analysis confirmed that the expression of AP-N in renal cancer tissues was also lower than in adjacent normal tissues. These results suggest that the immunohistochemical detection of MT and AP-N could provide useful information as a pathological diagnostic tool for classifying renal cancer and surrounding tissues.

Biomarkers, Tumor↗
PubMed2001

The carboxyl terminal sequence of nucleolar protein B23.1 is important in its DNA polymerase alpha-stimulatory activity.

The protein B23 is a major nucleolar phosphoprotein comprising two isoforms, B23.1 and B23.2, which differ only in their carboxyl-terminal short sequences, the N-terminal 255 residues being identical in both forms. Both B23.1 and B23.2 stimulated immunoaffinity-purified calf thymus DNA polymerase alpha in a dose-dependent manner. The stimulatory effect of protein B23.1, the longer isoform, was found to be 2-fold greater than that of B23.2. Purified DNA polymerase alpha bound tightly to a protein B23.1-immobilized column, while it bound weakly to a protein B23.2-immobilized column. Surface plasmon resonance studies by BIAcore further showed that protein B23.1 bound to the DNA polymerase alpha-(dA).(dT) complex more tightly than did protein B23.2. The protein B23 isoforms appear to interact directly with the DNA polymerase alpha protein and not through the bound nucleic acid. These observations indicated that protein B23 physically bound to the DNA polymerase alpha and stimulated the enzyme activity. Product analyses showed that protein B23 greatly enhanced the reaction both in amount and length of product DNA, whereas it did not significantly alter the processivity of polymerization. In contrast, protein B23 effectively protected DNA polymerase alpha from heat inactivation. These results suggest that protein B23 stabilizes DNA polymerase alpha that is detached from product DNA, allowing the enzyme to be recruited for further elongation. Moreover, experiments using various C-terminal deletion mutants of protein B23 indicated that 12 amino acids at the C-terminal end of B23.1, which are absent in B23.2, may be essential for the full stimulation of the DNA polymerase alpha.

Amino Acid Sequence↗
PubMed2001

Neural readaptation to Earth's gravity following return from space.

The consequence of exposure to microgravity on the otolith organs was studied by recording the responses of vestibular nerve afferents supplying the utricular otolith organ to inertial accelerations in four toadfish, Opsanus tau, sequentially for 5 days following two National Aeronautics and Space Administration shuttle orbital flights. Within the first day postflight, the magnitude of response to an applied translation was on average three times greater than for controls. The reduced gravitational acceleration in orbit apparently resulted in an upregulation of the sensitivity of utricular afferents. By 30 h postflight, responses were statistically similar to control. The time course of return to normal afferent sensitivity parallels the reported decrease in vestibular disorientation in astronauts following return from space.

Adaptation, Physiological↗
PubMed2001

Effect of probucol in lecithin-cholesterol acyltransferase-deficient mice: inhibition of 2 independent cellular cholesterol-releasing pathways in vivo.

Cellular cholesterol release takes place by at least 2 distinct mechanisms: the lecithin-cholesterol acyltransferase (LCAT)-driven net efflux by cholesterol diffusion and the generation of high density lipoprotein (HDL) with cellular cholesterol and phospholipid on the cell-apolipoprotein interaction. Therefore, LCAT deficiency impairs the former pathway, and the latter can be inhibited by probucol, which interferes with the apolipoprotein-cell interaction. Hence, probucol was given to the LCAT-deficient mice in the attempt to suppress both of these pathways. The mice were fed low (0.2%) and high (1.2%) cholesterol diets containing 0.5% probucol for 2 weeks. LCAT deficiency and probucol markedly decreased plasma HDL, and the effects were synergistic. Tissue cholesterol content was lower in the adrenal glands and ovaries in the LCAT-deficient mice and in the probucol-treated mice, suggesting that HDL is a main cholesterol provider for these organs. It was also moderately decreased in the spleen of the low cholesterol-fed female mice and in the thyroid gland of the low cholesterol-fed male mice. On the other hand, the esterified cholesterol content in the liver was substantially increased by the probucol treatment with a high cholesterol diet in the LCAT-deficient mice but not in the wild-type mice. Among the groups, there was no significant difference in the tissue cholesterol levels in other organs, such as the liver, spleen, thymus, brain, erythrocytes, thyroid gland, testis, and aorta, resulting from either LCAT deficiency or probucol. Thus, the apolipoprotein-mediated mechanism plays a significant role in the export of cellular cholesterol in the liver, indicating that the liver is a major site of the HDL assembly. Otherwise, tissue cholesterol homeostasis can largely be maintained in mice even when the assembly of new HDL is inhibited by probucol in the absence of LCAT. Nonspecific diffusion of cholesterol perhaps adequately maintains the homeostasis in the experimental condition.

Animals↗
PubMed2001

Antidiabetic effect of an acidic polysaccharide (TAP) from Tremella aurantia and its degradation product (TAP-H).

Continuous oral administration of the acidic polysaccharide (TAP) solution (0.5 g/l) and the TAP-H (degradation products of TAP) solution (1.5 g/l) instead of water for 10 weeks were found to depress plasma glucose increases in diabetes using genetically non-insulin-dependent diabetic model (KK-Ay) mice. TAP and TAP-H significantly lowered levels of insulin, total-cholesterol and triglyceride in the blood of the mice. In excretion to feces, TAP and TAP-H significantly increased the total bile acid, while the cholesterol content of both groups was less than that of the control. Furthermore, TAP and TAP-H significantly decreased the plasma lipoperoxide level. The study shows that TAP and TAP-H have an antidiabetic effect on diabetes model mice.

Animals↗
PubMed2001

Extract from Serenoa repens suppresses the invasion activity of human urological cancer cells by inhibiting urokinase-type plasminogen activator.

We used three human urological cancer cell lines, PC-3, LNCaP and SKRC-1, to investigate the effects of the extract from Serenoa repens (Palmae) on tumor cell invasion. The invasion activity of these cell lines was determined in vitro using a Transwell cell-culture chamber. The invasion activity of PC-3 cells into Matrigel was effectively suppressed by the extract at the concentration range of 1-10 microg/ml, while that of LNCaP and SKRC-1 cells was unaffected by the extract. The extract did not affect the viability, adhesion ability, or motility of the cell lines. uPA is more strongly expressed on the membrane fraction of PC-3 cells than that of LNCaP or SKRC-1 cells. The purified uPA activity is inhibited by the extract from S. repens in a dose-dependent manner, suggesting that the suppression of PC-3 cell invasion by the extract is based on an inhibition of the uPA activity which is necessary for tumor cell invasion. These data suggest that the extract from S. repens specifically inhibits the uPA activity and may therefore be useful for the therapeutic treatment of prostate cancer.

Enzyme Inhibitors↗
PubMed2001

Inhibition of aminopeptidase N (AP-N) and urokinase-type plasminogen activator (uPA) by zinc suppresses the invasion activity in human urological cancer cells.

Zinc is an essential heavy metal and is more abundant in human prostate and kidney than in other tissues. The effects of zinc on the invasion activity of human prostate and renal cancer cell lines, PC-3, LNCaP and SKRC-1, were investigated in vitro using a Transwell cell-culture chamber and were compared with specific protease inhibitors for MMPs, uPA and AP-N, respectively. The invasion activity of PC-3 cells was effectively suppressed by zinc and by all protease inhibitors in a dose-dependent manner. The invasion activity of LNCaP cells was almost unaffected by these inhibitors. In SKRC-1 cells, the invasion activity was strongly suppressed by MP03, although a moderate inhibition by zinc and bestatin was observed. The purified AP-N activity was strongly inhibited by zinc at a concentration similar to that suppressing the invasion activity of PC-3 cells and this inhibition by zinc was apparently competitive. Although the purified uPA activity was also inhibited by zinc, this inhibition was uncompetitive. AP-N was expressed abundantly on the membrane fraction of PC-3 cells among these cells tested, while its expression on the membrane fraction of SKRC-1 cells was weaker than that of PC-3 cells. The expression of uPA was also highest on the membrane fraction of PC-3 cells. These results suggest that AP-N and uPA may be involved in the invasion of human prostate cancer cells and that zinc probably participates in the invasion and metastasis of cancer cells through the regulation of the enzymatic activity of AP-N and uPA in human cancerous prostate.

Adenocarcinoma↗
PubMed2001

Successful catheter intervention for acute coronary syndrome in a patient with antiphospholipid syndrome.

Antiphospholipid syndrome (APS) has the clinical manifestations of systemic vascular thrombotic disorders. Although coronary events are infrequent, they have been described. Early coronary interventions and vein graft bypass frequently failed because of thrombosis. Here we present a case of successful coronary intervention and management of acute coronary syndrome under a strictly controlled coagulation state in an APS patient.

Anticoagulants↗
PubMed2001

[Detection of O,O,S-trimethyl phosphorodithioate, an impurity in phenthoate (PAP), in komatsuna].

An unknown peak (peak A) was detected in a mass chromatogram of komatsuna extract containing a high concentration of phenthoate (PAP), and it was considered to be O,O,S-trimethyl phosphorodithioate (OOS). Although it is generally known that OOS exists as an impurity in technical malathion and PAP, it has not been reported that OOS is present in crops. Since an OOS standard is not commercially available, OOS was separated and purified from commercial emulsifiable malathion. Peak A was confirmed to be OOS by GC/MS using the purified OOS. The concentration of OOS was estimated to be 0.02 microgram/g. It is supposed that OOS was detected in crops because they contained a high concentration of PAP residue.

Chromatography, Gas↗