Biomedical subjects

M Kato

Publications and source records attributed to M Kato.

At least 379 records · Page 21Linked to original sources

PubMed2000

Mechanism of anti-tumor effect of combination of bleomycin and shock waves.

We have previously reported marked enhancement of the cytocidal effect of bleomycin (BLM) on cancer cell suspensions in vitro by the combination with shock waves. In this study, we evaluated the synergistic effects on cancer cell proliferation and apoptosis in solid tumors. A spherical piezo-ceramic element was used as the shock wave source, with a pressure peak of 40 MPa. A human colon cancer cell line, SW480 was implanted onto the back of nude mice. Two thousand shock waves were administered to the tumor immediately following an intravenous injection of BLM at a dose of one-tenth of the LD(50). The tumor was extirpated at 3, 6, 12, 24, 72 h and 1 week following shock exposure. Cell proliferation and apoptosis were detected by Ki-67 using antibody MIB-1 and by the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick-end labeling (TUNEL) method. The lowest percentage (35.7%) of Ki-67-positive cells appeared 24 h following the treatment. The maximum apoptotic index was detected within 6 h following the treatment. Moreover, numerous large cells with enlarged nuclei were detected histologically. These results suggest that shock waves may enhance chemotherapeutic effects by increasing apoptosis and decreasing cell proliferation in the tumor tissue.

Animals↗

PubMed2000

Mapping of melanoma modifier loci in RET transgenic mice.

Transgenic mice carrying the RET oncogene under the control of the metallothionein promoter exhibit severe pigmentation of the whole skin and melanocytic tumors. The genetic background influences melanoma development in RET mice; founder mice crossed with BALB/c mice show decreased incidence and increased latency of melanocytic tumors, whereas progeny of C57BL/6 mice show the opposite effect. Using partially congenic RET mice on a C57BL/6 genetic background (N3/RET mice), we studied genetic linkage in (N3/RETxBALB/c)xN3/RET backcross mice. We mapped three melanoma modifier loci, on chromosome 1 (Melm1 and Melm2) and chromosome 11 (Melm3), that are linked with early melanoma incidence and latency. Mapping of Melm loci and of five additional regions on chromosomes 6, 8, 9, 12, and 13 indicated allelic imbalance in N3/RET mice, with a significant excess of BALB/c alleles, suggesting the presence of additional putative melanoma modifier loci on these chromosomes.

Allelic Imbalance↗

PubMed2000

Isolation and characterization of tetracycline-resistant clinical isolates of Helicobacter pylori.

Tetracycline is an important component of combination therapies for Helicobacter pylori eradication. Twenty-nine tetracycline-resistant isolates requiring MICs ranging from 4 to 16 microgram/ml were isolated from Korean (22 of 460) and Japanese (7 of 105) patients. Interestingly, all of the 29 tetracycline-resistant isolates exhibited cross-resistance to metronidazole, and the cross-resistance was transferred to tetracycline-sensitive H. pylori strains.

Drug Resistance, Multiple↗

PubMed2000

Analysis of rdxA and involvement of additional genes encoding NAD(P)H flavin oxidoreductase (FrxA) and ferredoxin-like protein (FdxB) in metronidazole resistance of Helicobacter pylori.

Metronidazole (Mtz) is a critical ingredient of modern multidrug therapies for Helicobacter pylori infection. Mtz resistance reduces the effectiveness of these combinations. Although null mutations in a rdxA gene that encodes oxygen-insensitive NAD(P)H nitroreductase was reported in Mtz-resistant H. pylori, an intact rdxA gene has also been reported in Mtz-resistant H. pylori, suggesting that additional Mtz resistance mechanisms exist in H. pylori. We explored the nature of Mtz resistance among 544 clinical H. pylori isolates to clarify the role of rdxA inactivation in Mtz resistance and to identify another gene(s) responsible for Mtz resistance in H. pylori. Mtz resistance was present in 33% (181 of 544) of the clinical isolates. There was marked heterogeneity of resistance, with Mtz MICs ranging from 8 to >/=256 microg/ml. rdxA inactivation resulted in Mtz MICs of up to 32 microg/ml for 6 Mtz-sensitive H. pylori strains and 128 microg/ml for one Mtz-sensitive strain. Single or dual (with rdxA) inactivation of genes that encode ferredoxin-like protein (designated fdxB) and NAD(P)H flavin oxidoreductase (frxA) also increased the MICs of Mtz for sensitive and resistant strains with low to moderate levels of Mtz resistance. fdxB inactivation resulted in a lower level of resistance than that from rdxA inactivation, whereas frxA inactivation resulted in MICs similar to those seen with rdxA inactivation. Further evidence for involvement of the frxA gene in Mtz resistance included the finding of a naturally inactivated frxA but an intact rdxA in an Mtz-resistant strain, complementation of Mtz sensitivity from an Mtz-sensitive strain to an Mtz-resistant strain or vice versa by use of naturally inactivated or functional frxA genes, respectively, and transformation of an Mtz-resistant Escherichia coli strain to an Mtz sensitive strain by a naturally functional frxA gene but not an inactivated frxA gene. These results are consistent with the hypothesis that null mutations in fdxB, frxA, or rdxA may be involved in Mtz resistance.

Amino Acid Sequence↗

PubMed2000

Regional differences in metronidazole resistance and increasing clarithromycin resistance among Helicobacter pylori isolates from Japan.

The patterns of antibiotic resistance in Helicobacter pylori were assessed in two different regions in Japan. Overall, prevalences of resistance to metronidazole and clarithromycin were 12.4 and 12.9%, respectively. While there was no difference in clarithromycin resistance, the prevalence of metronidazole resistance was significantly higher in Kyoto (23.8%) than in Sapporo (8.1%). From 1996 to 1999, the prevalence of metronidazole resistance did not change but the prevalence of clarithromycin resistance doubled (from 9.1 to 18.7%).

Adult↗

PubMed2000

Increases in leptin levels, sympathetic drive, and weight gain in obstructive sleep apnea.

Patients with obstructive sleep apnea (OSA) are frequently obese and are predisposed to weight gain. They also have heightened sympathetic drive. We reasoned that noradrenergic activation of beta(3)-receptors on adipocytes would inhibit leptin production, predisposing to obesity in sleep apnea. We therefore tested the hypothesis that obesity and predisposition to weight gain in OSA are associated with low levels of plasma leptin. We prospectively studied 32 male patients (43 +/- 2 yr) with OSA who were newly diagnosed and never treated and who were free of any other diseases. Control measurements were obtained from 32 similarly obese closely matched male subjects (38 +/- 2 yr). Leptin levels were 13.7 +/- 1.3 and 9.2 +/- 1.2 ng/ml in patients with OSA and controls, respectively (P = 0.02). Weight gain over the year before diagnosis was 5.2 +/- 1.7 and 0.5 +/- 0.9 kg in sleep apnea patients and similarly obese control subjects, respectively (P = 0.04). Muscle sympathetic activity was 46 +/- 4 and 30 +/- 4 bursts/min in patients with OSA (n = 16) and control subjects (n = 18), respectively (P = 0.01). Plasma leptin levels are elevated in newly diagnosed otherwise healthy patients with untreated sleep apnea beyond the levels seen in similarly obese control subjects without sleep apnea. Higher leptin levels in OSA, independent of body fat content, suggest that OSA is associated with resistance to the weight-reducing effects of leptin.

Adult↗

PubMed2000

Disparity selectivity of neurons in monkey inferior temporal cortex.

The inferior temporal cortex (IT) of the monkey, a final stage in the ventral visual pathway, has been known to process information on two-dimensional (2-D) shape, color, and texture. On the other hand, the dorsal visual pathway leading to the posterior parietal cortex has been known to process information on location in space. Likewise, neurons selective for binocular disparity, which convey information on depth, have been found mainly in areas along the dorsal visual pathway. Here, we report that many neurons in the IT are also selective for binocular disparity. We recorded extracellular activity from IT neurons and found that more than half of the neurons changed their response depending on the disparity added. The change was not attributed to monocular responses or eye movements. Most neurons selective for disparity were "near" or "far" cells; they preferred either crossed or uncrossed disparity, and only a small population was tuned to zero disparity. Disparity-selective neurons were also selective for shape. Most preferred the same type of disparity irrespective of the shape presented. Disparity preference was also invariant for the fronto-parallel translation of the stimuli in most of the neurons. Finally, nearby neurons exhibited similar disparity selectivity, suggesting the existence of a functional module for processing of binocular disparity in the IT. From the above and our recent findings, we suggest that the IT integrates shape and binocular disparity information, and plays an important role in the reconstruction of three-dimensional (3-D) surfaces.

Animals↗

PubMed2000

Role of secretory IgA, secretory component, and eosinophils in mucosal inflammation.

Eosinophils and their products are important in the pathophysiology of allergic inflammation in mucosal tissues. Secretory component (SC) bound to IgA mediates transepithelial transport of IgA. As another biological activity of SC, we have reported that secretory IgA (sIgA) and SC preferentially activate human eosinophils. When eosinophils were stimulated with immobilized sIgA, degranulation and superoxide production were greater than when stimulated with serum IgA. In contrast, neutrophils responded similarly to sIgA and serum IgA. Superoxide production by eosinophils stimulated with cytokines was enhanced synergistically by immobilized SC, while SC showed no effect on neutrophil activation. Eosinophil superoxide production stimulated with sIgA was abolished by anti-CD18 mAb, suggesting that beta2 integrins might be crucial for this reaction. There are several reports that SC and sIgA may play important roles in regulating eosinophil functions in vivo in diseases associated with mucosal eosinophilia and in various allergic diseases. It is speculated that eosinophils in the mucosa are activated by SC or sIgA, and that subsequent degranulation and superoxide production are induced.

Animals↗

PubMed2000

Stimulation of the beta(2) integrin, alpha(M)beta(2), triggers tyrosine phosphorylation and cellular degranulation on human eosinophils.

Activation of human eosinophils by specific extracellular stimuli triggers the cellular degranulation response. Because cellular adhesion is critical for this eosinophil degranulation, we have tested the hypothesis that ligation of the beta(2) integrin, alpha(M)beta(2) (Mac-1, CD11b/CD18), leads to intracellular signaling events that contribute to the eosinophil activation response. Recently, we found that engagement of beta(2) integrin using two different approaches, such as cell adhesion induced by IL-5 or direct ligation of alpha(M)beta(2), triggered tyrosine phosphorylation of Cbl, the product of the c-cbl proto-oncogene, paxillin, a cytoskeletal protein, an unidentified 115-kD protein, and subsequent cellular degranulation. The results of this study indicate that engagement of alpha(M)beta(2) on eosinophils triggers an intracellular signaling cascade leading to cellular degranulation. Tyrosine phosphorylation of Cbl, paxillin, and a 115-kD protein may play important roles in adhesion-dependent cellular functions of eosinophils.

CD18 Antigens↗

PubMed2000

Effects of sleep deprivation on neural circulatory control.

Effects of sleep deprivation on neural cardiovascular control may have important clinical implications. We tested the hypothesis that sleep deprivation increases heart rate, blood pressure, and sympathetic activity and potentiates their responses to stressful stimuli. We studied 8 healthy subjects (aged 40+/-5 years, 6 men and 2 women). Blood pressure, heart rate, forearm vascular resistance, and muscle sympathetic nerve activity were measured at rest and during 4 stressors (sustained handgrip, maximal forearm ischemia, mental stress, and cold pressor test). Measurements were obtained twice, once after normal sleep and once after a night of sleep deprivation. All measurements were obtained in a blinded, randomized manner. In comparison with normal sleep, sleep deprivation resulted in an increase in blood pressure (normal sleep versus sleep deprivation=82+/-8 versus 86+/-7 mm Hg, mean+/-SEM, P=0.012) and a decrease in muscle sympathetic nerve activity (normal sleep versus sleep deprivation=28+/-6 versus 22+/-6 bursts/min, P=0.017). Heart rate, forearm vascular resistance, and plasma catecholamines were not significantly changed by sleep deprivation, nor did sleep deprivation affect autonomic and hemodynamic responses to stressful stimuli. Sleep deprivation results in increased resting blood pressure, decreased muscle sympathetic nerve activity, and no change in heart rate. Thus, the pressor response to sleep deprivation is not mediated by muscle sympathetic vasoconstriction or tachycardia.

Adult↗

PubMed2000

Personality type and neural circulatory control.

Psychosocial factors, including type A personality, anger, hostility, and anxiety, have been implicated in the pathogenesis of cardiovascular disease. Abnormal sympathetic responses to stress may help explain the link between certain behavior patterns and cardiovascular disease. We tested the hypothesis that in normal humans, type A personality characteristics are associated with exaggerated heart rate, pressor, and sympathetic nerve responses to mental and physical stress. We measured heart rate, blood pressure, and muscle sympathetic nerve activity (obtained with direct intraneural recordings) at rest and during stress in 45 healthy subjects (19 men and 26 women, age 29.2+/-8.7 years) who had no chronic diseases and were taking no medications. Subjects were divided into tertiles based on type A scores. There were no significant differences in sympathetic or hemodynamic reactivity among the 3 different intensity levels of type A characteristics. Baseline measures and responses to stress tests were similar across the 3 groups. Sympathetic and hemodynamic changes during stress tests were also similar in subject groups stratified according to anger scale and cynicism scale. Sympathetic nerve and hemodynamic measurements at rest and during stress were not different in normal subjects with type A characteristics. Abnormalities in sympathetic or cardiovascular reactivity are unlikely to be implicated in any excess of cardiovascular disease in people with type A personality characteristics.

Adult↗

PubMed2000

Plasma soluble interleukin-2 receptor levels during and after upper abdominal surgery.

Soluble interleukin-2 (IL-2) receptor (sIL-2R) is reported to be up-regulated in inflammatory disorders. Although sIL-2R may modulate perioperative inflammatory responses, it remains unclear whether upper abdominal surgery affects plasma sIL-2R levels. We evaluated the influence of major abdominal surgery on plasma sIL-2R levels. Ten patients scheduled for upper abdominal surgery received anaesthesia with isoflurane, nitrous oxide, and epidural block. Plasma sIL-2R and IL-6 levels were determined at pre-anaesthesia, 0, 2, and 4 hours during surgery, and on postoperative days 1 (POD1) and 3 (POD3). The plasma levels of sIL-2R decreased significantly and achieved their minimum value at 4 hours (677.0 +/- 125.3 pg/ml, P < 0.01 compared to pre-anaesthesia value; 924.5 +/- 178.8 pg/ml, 95% confidence interval = 122.2-550.4). The plasma sIL-2R levels increased on POD1 (1336.5 +/- 174.0 pg/ml) and POD3 (1629.0 +/- 262.8 pg/ml), and reached a level significantly higher than the baseline (P < 0.05 and P < 0.001, 95% confidence interval = 93.4-730.6 and 402.8-1006.2, respectively). The plasma sIL-2R levels on POD3 significantly correlated with the peak IL-6 levels (r = 0.67, P < 0.05). The plasma sIL-2R levels on POD3 correlated with the amount of intraoperative bleeding (r = 0.66, P < 0.05). In conclusion, we found that major abdominal surgery induces characteristic changes in plasma soluble IL-2 receptor levels.

Abdomen↗

PubMed2000

Cytological characterization of a pituitary folliculo-stellate-like cell line, Tpit/F1, with special reference to adenosine triphosphate-mediated neuronal nitric oxide synthase expression and nitric oxide secretion.

An immortal nonhormone-producing cell line with a characteristic star-shaped morphology, named Tpit/F1, was derived from an anterior pituitary gland of a temperature-sensitive large T antigen transgenic mouse. To characterize Tpit/F1 cells, we performed cytological studies, which revealed that Tpit/F1 cells express the messenger RNAs of neruonal nitric oxide (NO) synthase, S-100 protein, basic fibroblast growth factor, and pituitary-restricted transcription factor. The Tpit/F1 cells response to pituitary adenylate cyclase-activating peptide comprised the stimulated secretion of interleukin-6. Furthermore, glucocorticoids stimulate glutamine synthase production by Tpit/F1 cells. Considering these cytological characteristics together with their morphology, we deduced that Tpit/F1 cells are derived from pituitary folliculo-stellate (FS) cells. Our cytophysiological analyses of Tpit/F1 cells revealed that intracellular Ca2+ increased dose dependently on ATP administration (0-100 microM), and that this effect did not require the presence of extracellular Ca2+ and was not abolished by treatment with gadolinium, a Ca2+ channel blocker. The ATP-induced increase in intracellular Ca2+ ([Ca2+]i) was completely abolished by treatment with the Ca2+-adenosine triphosphatase (Ca2+-ATPase) inhibitor thapsigargin, which suggests that ATP increases [Ca2+]i by mobilizing internally stored Ca2+ followed by an influx of Ca2+. Moreover, UTP was equipotent with ATP in causing the [Ca2+]i increase in Tpit/F1 cells. Also, the Ca2+ response was prevented by the phospholipase C inhibitor, U-73122, but not by its inactive analog, U-73343. From these results we therefore concluded that ATP acts on Tpit/F1 cells via P2Y2-purinoceptors. Interestingly, both neuronal nitric oxide synthase messenger RNA and NO secretion were increased by ATP administration (10 and 100 microM). These results suggest the biological significance of the topological colocalization of FS cells and endocrine cells. Namely, ATP is cosecreted with hormones from endocrine cells and stimulates NO production by FS cells, and the released NO may regulate neighboring endocrine cell and blood vessels.

Adenosine Triphosphate↗

PubMed2000

4-hydroxynonenal induces a cellular redox status-related activation of the caspase cascade for apoptotic cell death.

4-Hydroxynonenal (HNE), a diffusible product of lipid peroxidation, has been suggested to be a key mediator of oxidative stress-induced cell death. In this study, we partially characterized the mechanism of HNE-mediated cytotoxicity. Incubation of human T lymphoma Jurkat cells with 20-50 microM HNE led to cell death accompanied by DNA fragmentation. Western blot analysis showed that HNE-treatment induced time- and dose-dependent activation of caspase-8, caspase-9 and caspase-3. HNE-induced caspase-3 processing was confirmed by a flow cytometric demonstration of increased catalytic activity on the substrate peptide. HNE treatment also led to remarkable cleavage of poly(ADP-ribose) polymerase (PARP), which was prevented by pretreatment of cells with DEVD-FMK as a caspase-3 inhibitor. The HNE-mediated activation of caspases, cleavage of PARP and DNA fragmentation were blocked by antioxidants cysteine, N-acety-L-cysteine and dithiothreitol, but not by two other HNE-reactive amino acids lysine and histidine, or by cystine, the oxidized form of cysteine. HNE rapidly decreased levels of intracellular reduced glutathione (GSH) and its oxidized form GSSG, and these were also attenuated by the reductants. Coincubation of Jurkat cells with a blocking anti-Fas antibody prevented Fas-induced but not HNE-induced activation of caspase-3. HNE also activated caspase-3 in K562 cells that do not express functional Fas. Our results thereby demonstrate that HNE triggers oxidative stress-linked apoptotic cell death through activation of the caspase cascade. The results also suggest a possible mechanism involving a direct scavenge of intracellular GSH by HNE.

Aldehydes↗

PubMed2000

Effect of epinephrine on GLUT2 protein content in mouse liver.

The intraperitoneal administration of epinephrine (EP) to mice caused a significant increase in the blood glucose level and a significant decrease in the liver glycogen content 1 h after its administration at 0.6 mg/kg (blood glucose; p < 0.01, liver glycogen; p < 0.01). The liver type glucose transporter (GLUT2) mRNA expression and protein content from mouse liver significantly increased in the intraperitoneally EP-treated mice when compared to that in normal mice (mRNA; p < 0.01, protein; p < 0.01). These results suggest that the hyperglycemic effect of EP is due, at least in part, to the increase of GLUT2 protein synthesis.

Animals↗

PubMed2000

Focal cerebral ischemia-induced escape deficit in rats is ameliorated by a reversible inhibitor of monoamine oxidase-a: implications for a novel animal model of post-stroke depression.

The present investigation was conducted to examine whether a reversible inhibitor of monoamine oxidase (MAO)-A, T-794, affects the shuttle-box escape deficit induced by transient middle cerebral artery (MCA) occlusion (MCAO). MCA-occluded and sham-operated rats (surgery on day 0) were subjected to daily shuttle-box session from day 7 to 9 (training series) and from day 13 to 15 (test series) and received twice daily administration of T-794 (10 mg/kg p.o., b.i.d.) or vehicle from the evening of day 9. In the final shuttle-box session of test series (day 15), while MCA-occluded-vehicle-treated rats showed significantly more escape failures than sham-operated-vehicle-treated rats, the failures made by MCA-occluded rats were significantly decreased by T-794 to the level of the sham-operated group. Additionally, biochemical examination was conducted after behavioral evaluation to examine possible involvement of the brain monoamine system in the observed behavioral syndrome. In occluded hemisphere of MCA-occluded rats, catecholamine levels were decreased and ratios of deaminated metabolite to corresponding monoamine were increased compared with the respective values of the sham-operated group, and these changes were reversed by T-794. Results are discussed in terms of possible relevance of the MCAO-induced escape deficit to post-stroke depression.

Animals↗

PubMed2000

Synthesis of new synthons for organofluorine compounds from halothane containing sulfur functional groups.

To develop new synthons for the syntheses of organofluorine compounds, the treatment of Halothane, 2-bromo-2-chloro-1,1,1-trifluoroethane, (1) with 4-methylbenzenethiol (2) in the presence of sodium hydride gave 1-chloro-2,2,2-trifluoroethyl 4-methylphenyl sulfide (3), which was oxidized with m-chloroperbenzoic acid (m-CPBA) to the corresponding sulfoxide (4) and sulfone (5). Reaction of 3 and 5 with allyltributyltin in the presence of 2,2'-azobis(isobutyronitrile) (AIBN) gave 1-(trifluoromethyl)-3-butenyl compounds (9, 11). Sulfoxide 4 was decomposed in this condition. The treatment of 3 with allyltrimethylsilane in the presence of Lewis acids gave 1-(trifluoromethyl)-3-butenyl compounds (9) in good yield. This result suggests that 4-methylphenylthio substituent stabilizes the alpha-carbocation effectively, though the trifluoromethyl group destabilizes it strongly. Aromatic compounds similarly reacted with 3 in the presence of titanium(IV) chloride to give 2-aryl-1,1,1-trifluoro-2-(4-methylphenylthio)ethanes. Thus, sulfur compounds derived from Halothane were found to be useful new synthons for organofluorine compounds.

Halothane↗

PubMed2000

Effects of physical training on the recovery of the autonomic nervous activity during exercise after coronary artery bypass grafting: effects of physical training after CABG.

Analysis of heart rate variability (HRV) can identify patients at risk of sudden cardiac death after myocardial infarction. The present study examined the effect of 2 weeks of supervised aerobic exercise training on the recovery of the autonomic nervous activity, exercise capacity, and cardiac output (CO) after coronary artery bypass grafting (CABG). Twenty-eight patients were randomly divided into the training group or the control group and performed exercise tests at 1 week, 3 weeks, 3 months, 6 months and 1 year after CABG. The HRV was measured, and the high-frequency component of HRV was used as an index of parasympathetic nerve activity (PNA); the plasma norepinephrine concentration (NE) was used as an index of sympathetic nervous activity. Cardiac output was also measured. In the training group, peak VO2, peak CO and PNA during exercise had improved at 3 weeks, but there was no improvement in these indices in the control group. NE decreased 1 week after CABG in both groups. These results indicate that physical training soon after CABG improves not only the exercise capacity, but also PNA.

Aged↗