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T Mashimo

Publications and source records attributed to T Mashimo.

At least 91 records · Page 5Linked to original sources

Evaluation of effect of treatment for invasive bladder cancer by ultrasonography with intra-arterial infusion of carbon dioxide microbubbles.

RATIONALE AND OBJECTIVES: The purpose of this study was to evaluate the diagnostic usefulness of the ultrasonography with intra-arterial infusion of carbon dioxide microbubbles (CO2) for invasive bladder cancer. METHODS: Twelve patients with muscle-invading bladder cancer who were treated by concurrent radiotherapy and intra-arterial infusion of daily low dose of cisplatin using an implanted infusion port were included. A total of 30 studies was performed during the treatment to evaluate the visualization of the tumor and effect of the treatment compared with conventional ultrasonography, computed tomography, or cystoscopy. RESULTS: Satisfactory visualization of the tumor in CO2 ultrasonography was obtained in all patients, in particular in those with flat tumor or prostatic invasion. The enhancement effect of CO2 on the tumor, which was maintained well in the late period of the treatment, made possible evaluation of the therapeutic effect. With respect to the evaluation of local response, disagreement between clinical response and the evaluation of CO2 ultrasonography was observed in two patients with definite differentiation between wall edema and residual tumor after treatment being difficult. CONCLUSIONS: Carbon dioxide ultrasonography is easy to perform in patients treated with arterial infusion therapy using an implanted infusion port and provides practical information in evaluating therapeutic effect.

Aged↗

[Hemodynamic effects of amrinone combined with dopamine in patients undergoing living renal transplantation].

Systemic hypertension is a constant feature of chronic renal failure, mediated by renin and exacerbated by salt and fluid loading. Vascular atherosclerosis appears to accelerate in patients on long-term dialysis. Therefore, it is important to control hypertension and keep appropriate renal blood flow during living renal transplantation surgery. Amrinone, a phosphodiesterase inhibitor, produces vasodilation in arterial smooth muscle as well as venodilation in the capacitance bed. By increasing myocardial contractility it increases inotropic effect. Amrinone has potent inodilator effects because of its dual mechanism of action. The current study is aimed to compare hemodynamic effects between amrinone (3-5 mg.kg-1.min-1) (AMR group, n = 4) and nitroglycerin (0.3-1.0 mg.kg-1.min-1) (NTG group, n = 5), combined with dopamine (3-5 mg.kg-1.min-1) in nine patients undergoing living renal transplantation. Increase in cardiac index in AMR group was significantly larger than that in NTG group. Values of systemic and pulmonary vascular resistance in AMR group were significantly smaller than those in NTG group. No significant difference was found in renal function in the post-operative period.

3',5'-Cyclic-AMP Phosphodiesterases↗

The region responsible for stroke on chromosome 4 in the stroke-prone spontaneously hypertensive rat.

To detect genetic loci responsible for stroke susceptibility, we produced 107 male F2 progenies crossed between stroke-prone spontaneously hypertensive rats (SHRSP/Izm) and normotensive Wistar Kyoto rats (WKY/Izm) and followed them up until they developed cerebral stroke. One hundred and twenty-five simple sequence repeat (SSR) markers were analyzed in these F2 rats. Nine of 107 F2 rats suffered from macroscopically overt stroke. In these 9 rats, the segregation ratio of 3 genotypes at 6 SSR marker loci on chromosomes 2, 4, 9, and 10 was highly distorted from the expected value (the observed sp/sp:sp/wky:wky/ wky ratio was either 6:3:0 or 6:2:1, while the expected was 1:2:1, p < 0.01 by chi 2 test). Further, the brain weight was significantly heavier (p < 0.001) in the F2 rats suffering from stroke, suggesting that the brain weight was a parameter for stroke. The brain weight of F2 rats cosegregated with D4Mit19, D4Mgh7, and D4Mgh8 (p = 0.0015, 0.0014, and 0.0040 by ANOVA, respectively) on chromosome 4 supporting genetic effects of this genetic loci on the pathogenesis of cerebral stroke. Blood pressure did not cosegregate with these markers on chromosome 4. These results suggest that a region on chromosome 4, independently of hypertension, determines genetic susceptibility to cerebral stroke.

Animals↗

Cardiovascular effects of an ultra-short-acting nitric oxide-releasing compound, zwitterionic diamine/NO adduct, in dogs.

BACKGROUND: This study was conducted to clarify the cardiovascular effects of a new NO-releasing compound, NOC-7, and to compare it with other nitrovasodilators, sodium nitroprusside (SNP) and nitroglycerin, in dogs anesthetized with pentobarbital. METHODS AND RESULTS: A bolus injection of NOC-7 decreased mean aortic blood pressure in a dose-dependent manner. The onset was rapid and the recovery quick. Continuous infusion of NOC-7 decreased mean aortic pressure from 115 +/- 3.9 to 84 +/- 2.9 mm Hg and infusion of SNP, from 118 +/- 3.8 to 87 +/- 3.1 mm Hg. The optimum doses of NOC-7 and SNP were determined to be 2.73 +/- 0.77 and 11.5 +/- 6.1 micrograms.kg-1.min-1, respectively. During infusion of NOC-7, heart rate and cardiac output were increased (P < .05), pulmonary artery pressure was not changed, and systemic and pulmonary vascular resistances were decreased (P < .05). Electromagnetic flowmetry showed that portal venous and internal carotid arterial blood flow were increased (P < .05) and that hepatic and renal arterial blood flows were not changed. These hemodynamic changes during NOC-7 infusion were similar to those with SNP. The plasma level of NO2-/NO3 did not change, but methemoglobin increased slightly (P < .05). Comparison between hypotensive responses before and after a 3.5-hour infusion of NOC-7 or nitroglycerin showed that acute tolerance developed to nitroglycerin but not to NOC-7. CONCLUSIONS: The results indicate that NOC-7 may be useful as an ultra-short-acting nitrovasodilator that has no major adverse effect or tolerance.

Animals↗

A new nitric oxide donor, NOC-18, exhibits a nociceptive effect in the rat formalin model.

The utility of a new nitric oxide (NO) donor, NOC-18, and the contribution of the neurotransmitter NO to nociception in response to tissue injury in rats, were examined following the subcutaneous injection of formalin into the hindpaw. This model induces biphasic responses in pain-related behavior, such that C-fiber activation during the first phase triggers a state of central sensitization characterized by the second phase. Formalin-induced nociceptive behavior was facilitated by intracerebroventricular administration of NOC-18 in the second phase, but not the first phase. This enhancement was completely abolished by the soluble guanylate cyclase inhibitor, methylene blue. These findings indicate that NO causes nociception via the NO-cGMP pathway in the central nervous system and NOC-18 proved to be a convenient and useful tool for the investigation of nociception-related NO.

Animals↗

Antimicrobial activity of a 13 amino acid tryptophan-rich peptide derived from a putative porcine precursor protein of a novel family of antibacterial peptides.

It has long been speculated that porcine cathelin is an N-terminal fragment of a longer precursor protein which possesses antimicrobial activity. In an attempt to find such a precursor, a cDNA clone was recently isolated and sequenced by screening a cDNA library from porcine bone marrow. In order to identify the functional activity of the putative protein encoded by an open reading frame, we have synthesized various lengths of peptides that correspond to the C-terminal region of the protein and examined them for their antimicrobial activities. We found that a 13 amino acid tryptophan-rich region with the sequence of VRRFPWWWPFLRR had strong antimicrobial activity with a wide spectrum. It showed potency against Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumonia, Staphylococcus epidermidis, Proteus mirabilis, and Streptococcus group D as well as Aspergillus fumigatus. The action of this peptide is bactericidal rather than bacteriostatic and this activity is completely inhibited by 2 mM MgCl2. Our results indicate that the previously identified putative precursor encoded by the isolated cDNA indeed possesses a potent antimicrobial activity and that this 13 amino acid synthetic peptide is considered to be a potentially effective drug against various infectious agents.

Amino Acid Sequence↗

Direct inhibition of the actomyosin motility by local anesthetics in vitro.

Using a recently developed in vitro motility assay, we have demonstrated that local anesthetics directly inhibit myosin-based movement of single actin filaments in a reversible dose-dependent manner. This is the first reported account of the actions of local anesthetics on purified proteins at the molecular level. In this study, two tertiary amine local anesthetics, lidocaine and tetracaine, were used. The inhibitory action of the local anesthetics on actomyosin sliding movement was pH dependent; the anesthetics were more potent at higher pH values, and this reaction was accompanied by an increased proportion of the uncharged form of the anesthetics. QX-314, a permanently charged derivative of lidocaine, had no effect on actomyosin sliding movement. These results indicate that the uncharged form of local anesthetics is predominantly responsible for the inhibition of actomyosin sliding movement. The local anesthetics inhibited sliding movement but hardly interfered with the binding of actin filaments to myosin on the surface or with actomyosin ATPase activity at low ionic strength. To characterize the actomyosin interaction in the presence of anesthetics, we measured the binding and breaking force of the actomyosin complex. The binding of actin filaments to myosin on the surface was not affected by lidocaine at low ionic strength. The breaking force, measured using optical tweezers, was approximately 1.5 pN per micron of an actin filament, which was much smaller than in rigor and isometric force. The binding and breaking force greatly decreased with increasing ionic strength, indicating that the remaining interaction is ionic in nature. The result suggests that the binding and ATPase of actomyosin are governed predominantly by ionic interaction, which is hardly affected by anesthetics; whereas the force generation requires hydrophobic interaction, which plays a major part of the strong binding and is blocked by anesthetics, in addition to the ionic interaction.

Actins↗

Ketamine inhibits nitric oxide production in mouse-activated macrophage-like cells.

We have investigated the effects of ketamine on nitric oxide produced by activated macrophages using a murine macrophage-like cell line, J774. Cells were incubated for 18 h under stimulation with lipopolysaccharide and interferon-gamma or lipoteichoic acid and interferon-gamma, with various concentrations of ketamine (6-600 mumol litre-1). Nitric oxide production was assessed by measuring nitrite, a stable by-product of nitric oxide breakdown, in the medium. Other N-methyl-D-aspartate receptor antagonists, MK-801 (150 mumol litre-1) and dextromethorphan (150 mumol litre-1) were also tested. In addition, we studied the effects of ketamine on production of tumour necrosis factor-alpha by activated macrophages. Ketamine inhibited nitrite production dose-dependently with both lipopolysaccharide- and lipoteichoic acid-activated macrophages by up to approximately 65% at the highest ketamine concentration (600 mumol litre-1). Neither MK-801 nor dextromethorphan had an inhibitory effect. Ketamine also suppressed production of tumour necrosis factor-alpha. The data show that ketamine inhibited nitric oxide production by activated macrophages probably, in part, via inhibition of production of tumour necrosis factor-alpha, an autocrine stimulatory factor for nitric oxide production, but not via the NMDA receptor pathway, which is involved in neuronal nitric oxide production.

Anesthetics, Dissociative↗

Mode and site of analgesic action of epidural buprenorphine in humans.

This study was designed to clarify the site of analgesic action of epidural buprenorphine and its spinal segmental analgesia. Fifty patients undergoing gastrectomy were randomly assigned to five groups according to the dose of buprenorphine and route of administration: epidural saline group, epidural buprenorphine 2- and 4-micrograms/kg groups, and intravenous buprenorphine 2- and 4-micrograms/kg groups. The changes in pressure pain threshold (PPT) and visual analog scale (VAS) were compared within groups of patients receiving either buprenorphine, 2 or 4 micrograms/kg epidurally, and between groups of patients receiving buprenorphine 2 or 4 micrograms/kg either epidurally or intravenously. The PPT near the surgical incision was significantly greater (P < 0.05) in the epidural buprenorphine group compared to the intravenous group during the middle period (between 2 and 6 h after administration) of analgesia obtained after administration of buprenorphine. VAS response significantly (P < 0.05) decreased in the epidural group compared to the intravenous group at the same dose. In the smaller dose buprenorphine epidural group, PPT at the forehead (an index of systemic analgesia) exceeded the preoperative value during the 12 h after administration of buprenorphine. PPT near the surgical incision decreased by 30% from the preoperative value and did not exceed the preoperative value throughout the study. PPT at the forehead significantly exceeded the PPT changes measured near the surgical incision (an index of regional analgesia) (P < 0.05). In the larger dose buprenorphine epidural group, during the early period (up to 2 h after administration), PPT at the forehead increased by 30%-40%, while PPT near the surgical incision decreased by 10%-25% compared to the preoperative value (P < 0.01). However, in the middle period, there were no significant differences in the changes between PPT at the forehead and near the surgical incision. In the late period (more than 6 h after administration), PPT at the forehead maintained the level of preoperative value, whereas PPT near the surgical incision decreased by more than 25% from the preoperative value (P < 0.01). VAS value significantly (P < 0.01) decreased in the larger dose buprenorphine epidural group compared with that in the smaller dose group during the middle period. The larger dose of epidural buprenorphine provided better analgesia than the smaller dose. We conclude that epidural buprenorphine acts predominantly at the supraspinal region and produces spinal segmental analgesia in a dose-related manner.

Adult↗

Cosegregation of the new region on chromosome 3 with salt-induced hypertension in female F2 progeny from stroke-prone spontaneously hypertensive and Wistar-Kyoto rats.

1. We investigated candidate loci for salt-sensitive high blood pressure (BP) in F2 progeny from crossing Wistar-Kyoto and stroke-prone spontaneously hypertensive rats. 2. In female F2 progeny, systolic and diastolic BP on the 12th day and the seventh month after salt loading was strongly linked with the D3Mgh12 and D3Mgh6 loci on chromosome 3, respectively. 3. These loci were linked with BP only in female F2 progeny, not in males. 4. These results indicate that hormonal factors may influence salt sensitivity, particularly with respect to gender differences.

Animals↗

[Pharmacokinetics of propofol during liver transplantation in small pigs].

A study using 14C propofol showed that the liver is the main eliminating organ for the agent. The current study was designed to clarify pharmacokinetics of propofol during liver transplantation in pigs. Five small pigs weighing 25.4 +/- 2.5 kg were anesthetized with isoflurane (0.5-1.5%) and mechanically ventilated under muscle paralysis with pancuronium. In the anhepatic phase, veno-veno bypass was placed from the inferior vena cava and portal vein to the superior vena cava. We studied pharmacokinetic parameters following an intravenous bolus injection of propofol at 2 mg.kg-1 in each phase, i.e. the pre-anhepatic, anhepatic and post-anhepatic phase during liver transplantation. Pharmacokinetic analysis showed that total plasma clearance of propofol in the anhepatic phase was significantly lower than that in the post-anhepatic phase. The results suggest that propofol may be metabolized extrahepatically and can be used at reduced doses in the anhepatic phase during liver transplantation.

Anesthetics, Intravenous↗

A synthetic form of tracheal antimicrobial peptide has both bactericidal and antifungal activities.

We have chemically synthesized tracheal antimicrobial peptide (TAP) with 38 amino acids and examined efficacy of the peptide on various organisms. The synthetic peptide showed potent bactericidal effect on both gram positive and negative bacteria. The action of bactericidal effect was relatively quick and 99.9% of E. coli cells were killed within 90 minutes at a concentration of 2.5 micrograms/ml of TAP. The peptide also showed antifungal activity against both mycelia (Aspergillus fumigatus) and yeast (Candida albicans) forms of fungi. Our domain analysis with a series of synthetic peptides of various lengths indicates that 17 amino acid residues of the C-terminal end is the minimum functional domain of the bactericidal activity.

Amino Acid Sequence↗

NOC, a nitric-oxide-releasing compound, induces dose dependent apoptosis in macrophages.

The ability of exogenous nitric oxide (NO) to induce apoptosis in macrophages was analyzed using NOC, a NO-releasing compound, as a source of NO. Exogenous NO was shown to induce apoptosis in a dose dependent manner. Quantitative analysis revealed that the amount of NO required to induce apoptosis in more than half of macrophages exposed was 100 times larger than that for endogenous NO-induced apoptosis. NOC proved to be a convenient and useful tool for investigation of apoptosis related to NO.

Animals↗

Pulmonary resistance in dogs: a comparison of xenon with nitrous oxide.

Xenon (Xe) may cause an increase in airway resistance due to its high density and viscosity. The object of this study was to examine the effects of Xe on pulmonary resistance using dog models with normal and methacholine-treated airways. During anaesthesia 22 mongrel dogs' tracheas were intubated and the lungs were mechanically ventilated with 70% N2/30% O2 as a control gas. The gases 70% nitrous oxide (N2O), 50% N2O, 70% Xe and 50% Xe were administered in a random order for 25 min. Bronchoconstriction was produced by a continuous infusion of methacholine, 0.22 mg.kg-1.hr-1. Pulmonary resistance (RL) was calculated by the isovolume method using flow at the airway opening, volume and transpulmonary pressure. In normal dogs, RL breathing 70% Xe (mean +/- SEM, 0.84 +/- 0.12 cm H2O.L-1.sec-1) was greater (P < 0.05) than with 70% N2O, 50% N2O or control gas (0.61 +/- 0.08, 0.59 +/- 0.06 and 0.62 +/- 0.06 cmH2O.L-1.sec-1). Breathing 50% Xe the RL (0.77 +/- 0.10 cmH2O.L-1.sec-1) was not different from 50% N2O or control. Methacholine infusion increased RL 3.92 +/- 1.98 (mean +/- SD) times. The RL breathing 50% Xe (2.55 +/- 0.44 cmH2O.L-1.sec-1) was not greater than during 50% N2O or control (2.08 +/- 0.33 and 2.13 +/- 0.33 cmH2O.L-1.sec-1) in methacholine-treated dogs. The data suggest that inhalation of high concentrations of Xe increases airway resistance, but only to a modest extent in dogs with normal or methacholine-treated airways.

Airway Resistance↗

Analgesic and hypnotic effects of subanaesthetic concentrations of xenon in human volunteers: comparison with nitrous oxide.

The purpose of this study was to examine the effects of xenon and nitrous oxide in equipotent doses of 0.3 MAC on pain threshold and auditory response time in six healthy male volunteers. Compared with 100% oxygen inhalation, xenon and nitrous oxide significantly increased the pain threshold as measured by a radiant heat algometer. There was no significant difference in analgesic effects between xenon and nitrous oxide. Xenon significantly prolonged the response time to auditory stimuli compared with 100% oxygen, but nitrous oxide did not. The inhibitory effect of xenon on the auditory response time was significantly greater than that of nitrous oxide. The same six volunteers were studied to test if naloxone antagonized analgesia induced by xenon or nitrous oxide. The analgesic effects of xenon and nitrous oxide did not differ with or without naloxone.

Adult↗

Fourteen anonymous DNA markers of laboratory rats identified with arbitrarily primed polymerase chain reaction (AP-PCR).

In order to develop genetic markers in rats, arbitrarily primed polymerase chain reaction (AP-PCR) was performed with single primers originally designed for microsatellite loci, instead of primers with short-sized and arbitrary nucleotide sequences. Each primer generated reliable and reproducible segments under optimal conditions. The fourteen amplification products have been successfully mapped to rat chromosomes by either linkage analysis using backcross progeny or chromosomal assignment with somatic cell hybrids. All of the loci were located on different chromosomes from those of the microsatellite loci, suggesting that sequence-specifically designed single primers can produce anonymous segments of genomic DNA showing polymorphisms. These markers should contribute to finding linkages for traits of interest in rats.

Animals↗

Eosinophils infiltration in the rat seminal vesicle associated with estradiol-17-beta-related stromal proliferation.

We performed a histological quantitative analysis of collagen and smooth muscle in seminal vesicle (SV) stroma after Estradiol-17 beta (E2) administration to the immature castrated rat. On day 14 after E2 administration, collagen and smooth muscle had increased approximately five and fifteen times, respectively, over the baseline of day 0. On day 28 (14 days after the cessation of E2 administration), smooth muscle decreased to the same level as that on day 7, but collagen did not decrease during the 14 days after the cessation of E2 administration. As the proliferation of stroma, the infiltration of eosinophils was seen in the perigrandular stroma that consisted of rich collagen. The number of infiltrated eosinophils increased exponentially in the period in which collagen proliferated. But in the peripheral stroma which consists of rich smooth muscle, no eosinophil infiltration was seen. These results suggest that eosinophil infiltration into SV is related to E2 administration and to stromal proliferation, especially to collagen proliferation in this condition.

Animals↗