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Biomedical subjects

T Ando

Publications and source records attributed to T Ando.

At least 163 records · Page 9Linked to original sources
PubMed1999

A synthetic inhibitor of histone deacetylase, MS-27-275, with marked in vivo antitumor activity against human tumors.

Synthetic benzamide derivatives were investigated for their ability to inhibit histone deacetylase (HDA). In this study, one of the most active benzamide derivatives, MS-27-275, was examined with regard to its biological properties and antitumor efficacy. MS-27-275 inhibited partially purified human HDA and caused hyperacetylation of nuclear histones in various tumor cell lines. It behaved in a manner similar to other HDA inhibitors, such as sodium butyrate and trichostatin A; MS-27-275 induced p21(WAF1/CIP1) and gelsolin and changed the cell cycle distribution, decrease of S-phase cells, and increase of G1-phase cells. The in vitro sensitivity spectrum of MS-27-275 against various human tumor cell lines showed a pattern different than that of a commonly used antitumor agent, 5-fluorouracil, and, of interest, the accumulation of p21(WAF1/CIP1) tended to be faster and greater in the cell lines sensitive to MS-27-275. MS-27-275 administered orally strongly inhibited the growth in seven of eight tumor lines implanted into nude mice, although most of these did not respond to 5-fluorouracil. A structurally analogous compound to MS-27-275 without HDA-inhibiting activity showed neither the biological effects in cell culture nor the in vivo therapeutic efficacy. These results suggest that MS-27-275 acts as an antitumor agent through HDA inhibition and may provide a novel chemotherapeutic strategy for cancers insensitive to traditional antitumor agents.

Animals↗
PubMed1999

Route of TT virus infection in children.

TT virus (TTV) is a novel viral agent, detected recently in non-A to E hepatitis cases. Little is known about its natural history or routes of transmission in childhood. For the detection of serum TTV DNA, semi-nested polymerase chain reaction (PCR) was carried out using TTV-specific primers and TTV nucleotide sequences were determined by the dideoxy chain-mediated termination method. Five of the 70 children studied (including 20 hepatitis B virus [HBV] carriers, 40 children born to HBV carrier mothers and 10 children born to hepatitis C virus [HCV] carrier mothers) had serum TTV DNA. Three of the 5 children had siblings (4 in total), so that a total of 9 children were studied to determine the time of initial serum TTV DNA detection. In the 8 seropositive children, the time of serum TTV DNA detection ranged from 6 to 14 months after birth, and TTV DNA persisted thereafter throughout the follow-up period. The TTV DNA-negative child was assessed most recently at 6 months of age. TTV DNA was detected in only 2 of the 4 mothers tested (families 2 and 3). When 271-bp TTV DNA fragments from each of the 8 children were sequenced, the degree of homology between siblings in families 1-3 was 100%, 99.5%, and 92.3%, respectively. The degree of homology between child-mother pairs of families 2 and 3 was 99.5-100% and 62. 6-63.9%, respectively. The distribution of different TTV strains was consistent within families, except for family 3. None of the TTV-infected children had elevated levels of alanine aminotransferase or clinical signs of liver disease.

Adolescent↗
PubMed1999

Chiral HPLC resolution of monoepoxides derived from 6,9-dienes and its application to stereochemistry assignment of fruit-piercing noctuid pheromone.

The resolution of insect pheromonal cis-monoepoxy racemates derived from (Z,Z)-6,9-dienes was examined employing chiral HPLC columns, and the results showed that a normal-phase column (Chiralpak AD) was suitable for both 6,7- and 9,10-epoxides with a C(17)-C(23) straight chain, as was a reversed-phase column (Chiralcel OJ-R) for the 6, 7-epoxides. To determine the absolute configuration of each separated enantiomer applying a modified Mosher's method, the epoxy ring was opened by methanolysis, and the (1)H-NMR data of (S)- and (R)-MTPA esters of the methoxyalcohols produced were analyzed. Further, the hydrogenated product of each enantiomer was chromatographed on the OJ-R column referring to the corresponding authentic chiral compounds with a saturated chain, which were prepared by a Sharpless epoxidation reaction. These analyses showed that the levorotatory 6,7- and 9,10-epoxides with shorter t(R)s possess 6S,7R and 9R,10S configuration, respectively, and the dextrorotatory enantiomers with longer t(R)s possess the opposite configuration. Utilizing this chiral HPLC, it was revealed that an abdominal tip extract of the fruit-piercing moth, Oraesia excavata Butler (Lepidoptera: Noctuidae), included (9S,10R)-(Z)-9, 10-epoxy-6-henicosene as a main sex pheromone component. The synthetic 9,10-epoxide with this configuration, which was separated from the racemate, exhibited stronger activity in electrophysiological and field tests against male moths than the enantiomer.

Animals↗
PubMed1999

Effects of cytokines on cerebral neurotransmission. Comparison with the effects of stress.

Table 2 summarizes the reported responses of the HPA axis, as well as catecholamines and indoleamines to the cytokines discussed above. Cytokine administration to animals can elicit a number of effects on the brain, including neuroendocrine and behavioural effects, and also alters the metabolism of neurotransmitters. The most well documented effect is the activation by interleukin-1 (IL-1) of the hypothalamo-pituitary-adrenocortical (HPA) axis, which is accompanied by a stimulation of cerebral noradrenaline (NA) metabolism, probably reflecting increased NA secretion. IL-1 also stimulates indoleamine metabolism, most prominently increasing tryptophan concentrations, and increasing the metabolism of serotonin (5-hydroxytryptamine, 5-HT). IL-6 induces a short-lived activation of the HPA axis, and has effects on tryptophan and 5-HT similar to those of IL-1. Tumour necrosis factor alpha (TNF alpha) has effects on the HPA axis similar to those of IL-6, but affects NA and tryptophan only at high doses. Interferon alpha had no effects on the parameters studied. The effects of IL-1 are remarkably similar to those observed following administration of endotoxin (lipopolysaccharide, LPS), and infections, such as influenza virus. They also resemble quite closely the responses that are observed to stressors commonly studied in laboratory animals, such as electric shock or restraint. The major differences are: that the NA response to shock or restraint is very uniform throughout the brain, whereas that to IL-1, LPS or infection is significantly greater in the hypothalamus; and, responses in dopaminergic (DA) systems are normally observed to shock or restraint, with especially prominent responses in the limbic cortex, whereas DA responses are rarely observed in response to IL-1 and immune stimuli, and when they do occur, the mesocortical system is not selectively affected. The neurochemical responses to cytokines may underlie some of the endocrine and behavioural responses. The NA response to IL-1 is apparently related to the HPA activation, but not the hypophagia. The significance of the indoleaminergic responses is not known.

Animals↗
PubMed1999

Are Metallic Markers Necessary for Coronary Artery Bypass Grafts? A Study Using X-ray Computed Tomography and Selective Graft Angiography.

Using X-ray computed tomography (CT) and selective graft angiography, the authors studied the necessity of metallic markers in coronary artery bypass grafts on 45 patients (mean age 57.2 years) with 87 saphenous vein grafts. Eight patients had 17 markers. X-ray CT was performed after surgery using an apparatus with a 1-second scanning time. Noncontrast X-ray CT was performed on horizontal sections, at 5-mm intervals, from the lower margin of the aortic arch to the lower left ventricle. A contrast medium was then injected into the antecubital vein (3 ml/second, total 30 ml) in one cross-section at the level of bifurcation of the pulmonary artery. Aortography (60 degrees in the left anterior and oblique positions, 20 ml/second, total 40 ml) was performed concurrently. Selective graft angiography was taken in the same direction, using 4 cm right of the Judkins with reference to the aortographic image and position of five clips on the sternum. Aortography revealed 79 patent and 8 occluded grafts. Selective graft angiography was easily performed even in grafts without markers. A cross-section of the occluded graft could not be seen with X-ray CT. Grafts with markers were often masked by artifacts produced by markers on X-ray CT. The number of observed graft slices (marker-positive grafts) was only 1.2 +/- 1.1 slices, significantly (p < 0.01) lower than marker-negative grafts (4.1 +/- 3.1 slices). In particular, the number of marker-positive right coronary artery grafts was 0.4 +/- 0.9 slices. Four of five right coronary artery grafts were unobservable due to artifacts. In grafts without markers, sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of X-ray CT to graft patency were 100%, 85.7%, 98.4%, 100%, and 98.6%, respectively. This study suggests that metallic markers may not be necessary for coronary artery bypass grafts.

Journal Article↗
PubMed1999

Factors affecting the rectus femoris-patellar tendon Q-angle, measured using a computed tomographic scan.

We devised a method to measure the Q-angle (the angle between the rectus femoris and the patellar ligament), using computed tomography (CT), in 1993. In this study, I investigated the lateral shift at each point forming the angle as factors affecting the Q-angle. The study group consisted of 83 patients with recurrent patellar dislocation (83 lower limbs) and a control group of 55 healthy people (55 lower limbs). A lateral shift was found in the anterosuperior iliac spine (ASIS) in the dislocation group compared with the control group (P < 0.01). A lateral shift was also found in the anteroinferior iliac spine (AIIS) in the dislocation group compared with the control group (P < 0.05). A medial shift was found in the bottom of the groove of the femoral condyle in the dislocation group compared with the control group (P < 0.001). A lateral shift was also seen in the tibial tubercle of the dislocation group in comparison with the control group (P < 0.0001). Lateral shift of the tibial tubercle may be the main factor influencing the Q-angle, as measured by CT.

Adolescent↗
PubMed1999

Determination of age-related changes in human soluble interleukin 2 receptor in body fluids of normal subjects as a control value against disease states.

A highly sensitive enzyme-linked immunosorbent assay (ELISA) system was developed for human soluble interleukin-2 receptor (sIL-2R) with an ELISA-amplification system (ELAST((R))). The sensitivity of the new method was 20-fold higher than that without the amplification. Thus very low concentrations of sIL-2R in urine can be detected. With this method, serum and urine concentrations of sIL-2R were analyzed for healthy Japanese subjects with age 1-67 years. Mean sIL-2R concentrations in both serum and urine of children were significantly higher than those of adults. However, the concentrations of children showed a progressive decline to those of adults by the age of 15 years. There was no difference in the values between males and females. The results provide a control value of sIL-2R against those in disease states such as nephrotic syndrome. Since the trends in serum and urine were found to be similar, urinary sIL-2R measurement may provide sufficient information, without measuring the blood concentration.

Adolescent↗
PubMed1999

Association of a T-cell receptor constant alpha chain gene polymorphism with progression of IgA nephropathy in Japanese patients.

Immunogenetic studies have suggested the role of the T-cell receptor (TCR) in the development of immune-mediated diseases. We investigated whether a genetic polymorphism in the TCR constant alpha (Calpha) chain region might modify the susceptibility or progression of immunoglobulin A (IgA) nephropathy. The TCR Calpha chain genotype was studied in 213 Japanese patients with IgA nephropathy and 73 individuals from the general population. A polymerase chain reaction-based TaqI restriction fragment length polymorphism assay (TaqI RFLP) was applied on the 5' flanking region of the TCR Calpha first exon. The TaqI-undigested (t) and TaqI-digested (T) alleles showed similar genotype distributions between the patients with IgA nephropathy and controls (tt:Tt:TT = 16.9%:46.5%:36.6% in IgA nephropathy v 9.6%:58.9%:31.5% in controls; chi(2) = 1.9; P = not significant). To further investigate the role of TCR Calpha chain gene polymorphism in renal prognosis, we analyzed those patients with IgA nephropathy in whom renal status had been monitored for a period of more than 3 years (n = 182). According to outcome, two groups were formed. The stable (S) group included 98 patients with renal function that remained unchanged during an average follow-up of 10.7 +/- 0.4 (SE) years. The progressive (P) group (n = 84) included patients with progressively declining renal function, with an average follow-up of 11.9 +/- 0.5 years. The genotype distributions of the TCR Calpha chain gene polymorphisms between these two groups differed significantly (tt:Tt:TT = 25.5%:40.8%:33.7% in S v 10.7%:44.1%:45.2% in P; chi(2) = 7.0; P < 0.05). The frequency of the T allele was greater in the P group (67.3% in P v 54.1% in S; chi(2) = 6.6; P = 0.01). The TT or Tt genotypes were more commonly observed in patients from the P group (89.3% of T allele carriers in P v 74.5% in S; chi(2) = 6.5; P = 0.01). It appeared the T allele might foreshadow a poor renal prognosis, conferring a potential risk for developing renal failure with time (odds ratio, 2.7; confidence interval, 1.2 to 6.0; P < 0.05). In summary, TCR Calpha chain genetic variability was associated with loss of renal function over time in patients with IgA nephropathy. In conclusion, the TCR Calpha chain polymorphism might prove helpful to predict progression to chronic renal failure in Japanese patients with IgA nephropathy.

Adult↗
PubMed1999

Damage to the cytoplasmic membrane of Escherichia coli by catechin-copper (II) complexes.

In the presence of a nonlethal concentration of Cu(II), washed Escherichia coli ATCC11775 cells were killed by (-)-epigallocatechin (EGC) and (-)-epicatechin (EC). Cell killing was accompanied by a depletion in both the ATP and potassium pools of the cells, but the DNA double strand was not broken, indicating that the bactericidal activity of catechins in the presence of Cu(II) results from damage to the cytoplasmic membrane. Induction of endogenous catalase in E. coli cells increased their resistance to being killed by the combination of catechins and Cu(II). In all cases studied, EGC and EC with Cu(II) were found to generate hydrogen peroxide, but its concentration was too low to account for the bactericidal activity. The bactericidal activity of EGC in the presence of Cu(II) was completely suppressed by ethylenediaminetetraacetate, bathocuproine, catalase, superoxide disumutase (SOD), heated catalase, and heated SOD, but not by dimethyl sulfoxide. When catalase, either heated or unheated, was added to the cells incubated with EGC in the presence of Cu(II), it completely inhibited further killing of the cells. These findings suggest that recycling redox reactions between Cu(II) and Cu(I), involving catechins and hydrogen peroxide on the cell surface, must be important in the mechanism of the killing.

Catalase↗
PubMed1999

Sonochemical and photochemical reactions of bromotrichloromethane in the presence and absence of 1-alkene.

Comparison between sonolysis and photolysis of bromotrichloromethane in the presence and absence of 1-alkenes was performed to elucidate the characteristics of homogeneous sonochemistry. Results indicate that the photolysis of BrCCl3 generates radicals in a homogeneous and dispersed state, while sonolysis generates them in a heterogeneous and localized state. In the photochemical reaction the BrCCl3-adduct was obtained over a wide range of mole fractions of BrCCl3, whereas in the sonochemical reaction the yield of the BrCCl3-adduct showed a sharp maximum in a range of high mole fractions of BrCCl3. This may be attributed to the large variation in surface tension.

Journal Article↗
PubMed1999

Structural requirements for alkylglycoside-type renal targeting vector.

PURPOSE: We have previously shown Glc-S-C7-Me (octyl beta-D-thioglucoside) exhibits renal targeting potential in vivo in addition to its specific binding to the renal membrane fraction in vitro. Thus, "alkylglycoside" is considered to be a novel targeting vector for the kidney (1,2). The present study is designed to clarify the structural requirements for alkylglycoside as a renal targeting vector. METHODS: Inhibitory effects of various sugars and glycosides on 3H-Glc-S-C7-Me binding to the kidney membrane fraction were evaluated by a centrifugation method. RESULTS: As far as the sugar moiety is concerned, no other sugars except D-aldohexose and D-aldohexose derivatives (containing F, S, and N) showed greater inhibition than D-glucose. Therefore, octylthio derivatives of various D-aldohexose were prepared and their inhibitory effects were investigated. The following findings were obtained: Equatorial OH at 4 position is essential; OH at 2 position can have either orientation or be deleted. As far as the alkyl moiety is concerned, the length, branching and electrical environment in the region of the glycoside bond are important; aromatic structures can substitute for the alkyl portion; the preferred glycoside bonding atom is as follows: S > NH > O. CONCLUSIONS: The structural requirements for the renal targeting vector have been identified to be as follows: a hydrophobic group (alkyl chain or aromatic ring) should be introduced to a sugar (D-glucose, D-mannose, or 2-deoxy-D-glucose) via a beta-glycoside binding atom (S > NH > O).

Animals↗
PubMed1999

Single-fluorophore imaging with an unmodified epifluorescence microscope and conventional video camera

Single fluorophores in aqueous solution were imaged in real time with a conventional silicon-intensified target video camera connected to an unmodified commercial microscope (IX70, Olympus) with epifluorescence excitation with a high-pressure mercury lamp. Neither a powerful laser nor an extremely sensitive video camera was required. Three experimental systems were used to demonstrate quantitatively that individual, moving or stationary Cy3 fluorophores could be imaged with the microscope: Cy3-gelsolin attached to an actin filament sliding over heavy meromyosin, sliding actin filaments sparsely labelled with Cy3, and heavy meromyosin labelled with one or two Cy3 fluorophores. The results should encourage many laboratories to attempt 'single-molecule physiology' in which the functions and mechanisms of molecular machines are studied at the single-molecule level in an environment where the biological machines are fully active.

Journal Article↗
PubMed1999

Increased mucosal production of granulocyte colony-stimulating factor is related to a delay in neutrophil apoptosis in Inflammatory Bowel disease.

Tissue accumulation of polymorphonuclear neutrophils (PMN) in Inflammatory Bowel disease (IBD) might be, in part, due to a delay in apoptotic processes associated with the effects of their specific growth factors and inflammatory cytokines. We addressed this hypothesis by examining the activity of granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage CSF (GM-CSF) in the organ culture supernatants of colonic mucosal specimens and their regulatory effects on PMN apoptosis in patients with IBD. The contents of G-CSF and GM-CSF in the supernatants were measured by the enzyme-linked immunosorbent assays and PMN apoptosis was evaluated by acridine orange/ethidium bromide staining, respectively. Mucosal specimens obtained from patients with active IBD exhibited higher levels of G-CSF and GM-CSF activity than controls. Notably, the levels of G-CSF activity were approximately 1000-fold higher than those of GM-CSF activity. Freshly isolated PMN showed a time-related increase in the proportion of cells with characteristic features of apoptosis when they were incubated with the culture medium alone and exposure of PMN to recombinant G-CSF and GM-CSF caused a concentration-dependent inhibition of apoptosis. Incubation of PMN with the supernatants from patients with active IBD induced an inhibitory effect on PMN apoptosis; this effect was abrogated to a significant degree by pre-incubation of the supernatants with anti-G-CSF serum. This study suggests that PMN apoptosis may be delayed under the influence of soluble mediators, especially G-CSF, in the microenvironment of IBD-affected mucosa, thus providing possible mechanisms for tissue accumulation of PMN in IBD.

Acridine Orange↗
PubMed1999

Mucosal macrophage inflammatory protein-1alpha activity in Helicobacter pylori infection.

Mucosal chemokines are considered to be important in the pathogenesis of Helicobacter pylori-associated gastritis. The aims of this study are to examine the levels of macrophage inflammatory protein-1alpha (MIP-1alpha) in organ cultures, the expression of MIP-1alpha mRNA and the cellular source of MIP-1alpha, using the antral mucosal specimens obtained from H. pylori-positive and -negative patients. Enzyme-linked immunosorbent assay was used to measure the levels of MIP-1alpha in organ cultures of mucosal tissues and cell cultures of fractionated mucosal cells. The expression of MIP-1alpha mRNA and protein was analysed in fresh biopsy tissues with reverse transcriptase-polymerase chain reaction (RT-PCR) and double immunofluorescence microscopy, respectively. The mucosal specimens obtained from H. pylori-positive patients exhibited significantly higher values of MIP-1alpha activity in organ cultures with increased numbers of CD68+ macrophages, myeloperoxidase+ neutrophils and mononuclear cells in the lamina propria compared with those from H. pylori-negative patients. The RT-PCR analysis detected MIP-1alpha mRNA in more than 50% of the specimens with H. pylori infection, but not in those without infection. In cell cultures, the macrophage fraction contained substantially higher amounts of MIP-1alpha on a per cell basis than the lymphocyte fraction and MIP-1alpha activity was not detected in cultures of gastric epithelial cells. This observation was also confirmed by a double immunofluorescence microscopic study in which most (>90%) MIP-1alpha-positive infiltrating cells were CD68+ macrophages. This study indicates that synthesis and secretion of MIP-1alpha are increased in H. pylori-infected antral mucosa and that mucosal macrophages are the main cell type responsible for this phenomenon.

Adult↗
PubMed1999

Interleukin-6 and soluble interleukin-6 receptor in the colonic mucosa of inflammatory bowel disease.

BACKGROUND: Interleukin-6 (IL-6) has multiple immunological effects on a wide variety of cells and tissues. The expression of IL-6 and IL-6 receptor (IL-6R) may be important to the pathogenesis of inflammatory bowel disease (IBD). METHODS: In the present study, we examined whether mucosal IL-6 and soluble IL-6R were associated with the pathophysiology of IBD using the colonic mucosal specimens obtained from patients with IBD. Enzyme-linked immunosorbent assay was used to measure the levels of IL-6 and sIL-6R in organ cultures of mucosal tissues and in cell cultures of fractionated mucosal cells as well as in the serum. Expression of IL-6 and IL-6R was analysed by reverse transcription-polymerase chain reaction analysis using freshly isolated lamina propria mononuclear cells (LPMC). RESULTS: The levels of IL-6 and sIL-6R in organ cultures were substantially elevated in patients with IBD, especially in those with histologically active inflammation. In contrast, considerably higher levels of sIL-6R were detected in patients with other types of colonic inflammation who were included as inflammatory controls, but elevation of IL-6 was less prominent in such patients. The positivity for expression of IL-6 and IL-6R mRNA in LPMC was in parallel with the results obtained in organ cultures. In cell cultures, mucosal macrophages were the main cell type producing both IL-6 and sIL-6R on a per cell basis and other cell fractions including colonic epithelial cells and lymphocytes produced substantially lower amounts of these molecules. The levels of IL-6 and sIL-6R in organ cultures, but not those in the serum, showed a significantly positive correlation with the degree of clinical disease activity in patients with IBD. CONCLUSIONS: Enhanced IL-6/sIL-6R-mediated immune and inflammatory responses may be implicated, at least partly, in the continuation of intestinal inflammation in patients with IBD.

Adolescent↗