Protective effect of University of Wisconsin solution on lipid peroxidation of liver grafts in reperfusion injury.
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Adenosine↗
Biomedical subjects
M Kanno
Publications and source records attributed to M Kanno.
Role of neutrophils in lipid peroxidation at reperfusion in liver transplantation.
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Animals↗
Alpha 1-adrenoceptor subtype distribution and the coupling to phosphoinositide hydrolysis in rat and rabbit ventricular myocardium.
The relative contributions of the alpha 1A- and alpha 1B-adrenoceptor subtypes to the stimulation of phosphoinositide (PI) hydrolysis in rat and rabbit ventricular myocardium were defined pharmacologically using WB-4101 and chloroethylclonidine (CEC). Radioligand binding experiments with [3H]prazosin showed that the maximum number of alpha 1A-adrenoceptors in rat myocardium was about ten times higher than in rabbit myocardium. The proportion of the two [3H]prazosin binding sites with high and low affinity for WB-4101 was similar in the two species: approximately 30% of the alpha 1-adrenoceptor population was pharmacologically alpha 1A and approximately 70% was alpha 1B. Phenylephrine produced concentration-dependent stimulation of PI hydrolysis in rat ventricular strips as measured by [3H]inositol monophosphate accumulation, but this stimulation was much less in rabbit. In both of the two species, WB-4101 was very effective in inhibiting phenylephrine-stimulated PI hydrolysis, whereas CEC had a minimal effect. Altogether, the degree of PI hydrolysis appears to be determined by the density of myocardial alpha 1-adrenoceptors. However, despite the greater density of the alpha 1B-subtype, it is the alpha 1A-subtype that is mainly coupled to PI hydrolysis in mammalian myocardium.
Adrenergic alpha-Agonists↗
Lack of the relationship between menstrual status and timing of surgery in survival of premenopausal patients with breast cancer.
To clarify the relation between menstrual cycle at surgery for breast cancer and prognosis, we have retrospectively investigated 159 women with premenopausal breast cancer. The end of follicular phase was determined putatively as 15 days before the coming menstrual period, and the luteal phase was assumed to commence with the fourteenth day. The mean observation period was 49.7 months. At surgery, 86 patients were in the follicular phase and 73 in the luteal. There was no difference in distribution of age, family history, parity, tumor size or nodal status between the two groups. There were no differences in disease-free or overall survival rate. The follow-up period was not sufficient, but the current result found no relation between the timing of surgery and prognosis.
Adult↗
The evaluation of mammographic microcalcification as biological malignancy in breast cancer.
The biological significance of mammographic microcalcification (MM) was investigated in breast cancer. 119 (39.8%) had evidence of microcalcification, while 170 were negative. Fifty-three (44.5%) of those with MM had nodal metastases. There is no significant correlation between MM and nodal metastases. Five-year survival of patients with MM was significantly shorter than that without. This suggests that MM may be of biological significance in breast cancer, and thereby attention should to be paid to assessing breast cancer patients with mammographic microcalcification.
Adult↗
mel-18, a Polycomb group-related mammalian gene, encodes a transcriptional negative regulator with tumor suppressive activity.
The mammalian mel-18/bmi-1 gene products share an amino acid sequence and a secondary structure, including a RING-finger motif, with the Drosophila Polycomb group (PcG) gene products Psc and Su(z)2, implying that they represent a gene family with related functions. As Drosophila PcG gene products are thought to function as transcriptional repressors by modifying chromatin structure, Mel-18/Bmi-1 might be expected to have similar activities. Here we have analyzed the function of mel-18 and found that Mel-18 acts as a transcriptional repressor via its target DNA sequence, 5'-GACTNGACT-3'. Interestingly, this binding sequence is found within regulatory or non-coding regions of various genes, including the c-myc, bcl-2 and Hox genes, suggesting diverse functions of mel-18 as the mammalian homolog of the PcG gene. We also demonstrate that mel-18 has tumor suppressor activity, in contrast to bmi-1, which has been defined as a proto-oncogene.
3T3 Cells↗
Phorbol esters elicit Ca(2+)-dependent delayed contractions in diabetic rat aorta.
To determine whether diabetes alters vascular effects mediated by activation of protein kinase C, the contractions induced by phorbol esters were examined in aortic rings from rats with 8- to 12-weeks streptozotocin-induced diabetes and compared with those from age-matched control rats. In diabetic rat aorta, phorbol 12,13-dibutyrate (PDB) (> or = 30 nM) and 12-O-tetradecanoylphorbol 13-acetate (TPA) (300 nM) elicited a delayed, sharply developing rise in tension following an initial gradually developing contraction. In control rat aorta, these agents produced only an initial slowly developing contraction. Both the initial and the delayed contractile responses observed in diabetic aorta were completely abolished by pretreatment with 20 nM staurosporine, and the delayed phase of contraction was not seen in Ca(2+)-free medium or in the presence of 1 microM nifedipine. The concentration-response curves for the contractions induced by PDB revealed that PDB at concentrations > or = 30 nM produced significantly greater responses in diabetic aorta than in control aorta. In control aorta, exposure to Ca(2+)-free medium and pretreatment with 1 microM nifedipine shifted the concentration-response curves for PDB to the right without changing the maximal response. Under these conditions, there were no differences in the curves for PDB in control and diabetic aortas. These results suggest that the appearance of the delayed phase of contraction, possibly due to a delayed opening of Ca2+ channels, during activation of protein kinase C may be responsible for the enhanced contractile responses to phorbol esters in diabetic rat aorta.
Alkaloids↗
Endothelin-1 does not phosphorylate phospholamban and troponin I in intact beating rat hearts.
To determine a role of phosphorylation of specific cardiac regulatory proteins in the positive inotropic effect of endothelin-1, we examined phosphorylation of sarcoplasmic reticulum and myofibrillar proteins in perfused beating rat hearts treated with endothelin-1. In parallel experiments, the effects of isoprenaline and phorbol-12,13-dibutyrate (PDB) on protein phosphorylation were also tested. In 32Pi-labeled hearts, perfusion with isoprenaline (100 nM) caused 4.4- and 10.4-fold increases in the degree of phosphorylation of phospholamban in sarcoplasmic reticulum and of troponin I in myofibrils, respectively. In contrast, neither endothelin-1 (100 nM) nor PDB (1 microM) significantly changed the phosphorylation state of these proteins. These findings provide evidence that phosphorylation of major cardiac regulatory proteins is not responsible for the positive inotropic action of endothelin-1.
Animals↗
Prognostic factors associated with differentiated thyroid cancer.
A multivariate analysis was conducted on the survival data of 180 patients who underwent curative resection for differentiated thyroid cancer between 1966 and 1987, and the 10- and 20-year survival rates were found to be 80.6% and 73.1%, respectively. A survival analysis was also performed, testing the following factors: the patient's age at the time of diagnosis, tumor size, extraglandular extension, nodal status, distant metastases, operative procedure, sex, and histology. A univariate analysis found the initial six factors to be significant prognostic variables, but the latter two to be of no significance. On the other hand, the multivariate analysis showed that distant metastases, age, and tumor size were the most significant prognosticators. Thus, the age of the patient should be taken into consideration during the follow-up of treatment for differentiated thyroid cancer.
Adenocarcinoma, Follicular↗
Case report of a patient with multiple lesions of the stomach, including multiple cancers and an adenomatous polyp.
This paper describes an unusual case of an 80-year-old man followed up for multifocal gastric cancers. There were three separate polypoid carcinomas and one adenomatous polyp with no sign of malignancy. We measured the DNA content of the gastric cancer and adenomatous cells obtained from endoscopically biopsied specimens. The adenomatous polyp and one of the cancerous lesions showed DNA diploidy. The other two cancerous lesions showed DNA aneuploidy, with different DNA index (DI) values (1.12 and 1.64, respectively). It is considered that the three cancers arose from different stem lines. However, an operation was not performed because the patient refused gastrectomy, and therefore only conservative follow up has been continued. Presentation of this case is followed by a detailed discussion focusing on the possible development of carcinoma in gastric adenomatous polyps in view of the data from the literature.
Adenomatous Polyps↗
TCR repertoire in early fetal mouse thymus.
We investigated the rearrangement and expression of TCR genes in mouse fetal thymus organ culture, a system that avoids subsequent entry of hematopoietic precursor cells. The first observable rearranged TCR gene was homogeneous V gamma 2-J gamma 2, detectable as early as fetal day 11 (d11) in the thymic primordia. The productive TCR was homogeneous V gamma 5-J gamma 1, first detectable in d13 thymocytes, followed by adult-type TCR gamma (V gamma 4 and V gamma 7). Sequence analysis of TCR revealed five types of V-J junctional sequences. In the very early stage, a homogeneous V-J junction is generated via a short homology sequence in the coding region (Type I), while a short homology sequence in the P-nucleotide rather than the coding region is used in the following stage (Type II). In the later embryonic stages, diverse V-J junctions are generated by well-known mechanisms, such as P-nucleotide (Type III), N-region insertion (Type IV) or trimming of the coding ends (Type V). These findings suggest that the generation of homogeneous TCR gamma (V gamma 2 and V gamma 5) in the early fetal stages is due to the intrinsic rearrangement mechanisms and is in stage specific manner.
Animals↗
Renal function in patients with high serum fluoride concentrations after prolonged sevoflurane anesthesia.
BACKGROUND: In studies of methoxyflurane-induced nephrotoxicity, renal-concentrating impairment has been observed only when serum inorganic fluoride concentrations exceed 50 microM. Prolonged sevoflurane anesthesia can result in serum inorganic fluoride concentrations in excess of 50 microM. The authors compared renal function after prolonged sevoflurane anesthesia with that after isoflurane anesthesia. In addition, they measured urinary excretion of N-acetyl-beta-glucosaminidase (NAG), a sensitive index of renal tubular damage, during the 3-day period after anesthesia. METHODS: Thirty-four healthy patients who underwent either sevoflurane (23 patients) or isoflurane (11 patients) anesthesia at a total gas flow of 61/min for orthopedic surgery scheduled to last at least 5 h were studied. At 16.5 h after cessation of anesthesia, patients were administered 10 units of vasopressin and urine was collected frequently thereafter for evaluation of urinary osmolality. In addition, urinary excretion of NAG was measured before and on days 1-3 after anesthesia. Based on whether peak fluoride concentrations exceeded 50 microM, 23 patients anesthetized with sevoflurane were assigned to a sevofluranehigh group (> 50 microM) or a sevofluranelow (< 50 microM) group. RESULTS: The eight patients in the sevofluranehigh group had a mean peak fluoride concentration of 57.5 +/- 4.3 microM. A significant, albeit weak, inverse correlation was found between peak fluoride concentration and maximal urinary osmolality after the injection of vasopressin (r = -0.42, P < 0.05). Mean maximum urinary osmolality tended to be lower in the sevofluranehigh group (681 +/- 60 mOsm/kg) than in the other two groups after administration of vasopressin, although the difference among the three groups did not quite reach a statistical significance (P = 0.068). One patient had a transient concentrating defect (maximum urinary osmolality = 390 mOsm/kg) on day 1 after anesthesia. Urinary excretion of NAG in both the sevofluranehigh and sevofluranelow groups was greater on days 2 and 3 after anesthesia than before anesthesia. The increase in urinary NAG excretion was dose related with sevoflurane, but there was no difference in results of routine laboratory renal tests on days 2 and 3 after anesthesia among the three groups. CONCLUSIONS: The authors concluded that sevoflurane anesthesia results in increased serum fluoride concentration, a tendency toward decreased maximal ability to concentrate urine, and increased excretion of NAG. However, the increase in urinary NAG excretion was not indicative of clinically significant renal damage in these patients with no preexisting renal disease.
Acetylglucosaminidase↗
Cyclic GMP-mediated inhibition of L-type Ca2+ channel activity by human natriuretic peptide in rabbit heart cells.
1. Effects of atrial natriuretic peptide (ANP) on the L-type Ca2+ channels were examined in rabbit isolated ventricular cells by use of whole-cell and cell-attached configurations of the patch clamp methods. ANP produced a concentration-dependent decrease (10-100 nM) in amplitude of a basal Ca2+ channel current. 2. The inactive ANP (methionine-oxidized ANP, 30 nM) failed to decrease the current. 3. 8-Bromo-cyclic GMP (300 microM), a potent activator of cyclic GMP-dependent protein kinase (PKG), produced the same effects on the basal Ca2+ channel current as those produced by ANP. The cyclic GMP-induced inhibition of the Ca2+ channel current was still evoked in the presence of 1-isobutyl-3-methyl-xanthine, an inhibitor of phosphodiesterase. ANP failed to produce inhibition of the Ca2+ channel current in the presence of 8-bromo-cyclic GMP. 4. In the single channel recording, ANP and 8-bromo-cyclic GMP also inhibited the activities of the L-type Ca2+ channels. Both agents decreased the open probability (NPo) without affecting the unit amplitude. 5. The present results suggest that ANP inhibits the cardiac L-type Ca2+ channel activity through the intracellular production of cyclic GMP and then activation of PKG.
1-Methyl-3-isobutylxanthine↗
Inotropic changes induced by fluoroaluminates in rabbit left atrial muscles: possible involvement of G proteins.
1. The effects of fluoroaluminate complexes (NaF plus AlCl3) on force of contraction, cyclic AMP accumulation and phosphoinositide hydrolysis were examined in rabbit left atrial muscles. 2. Fluoroaluminates (1-10 mM NaF + 10 microM AlCl3) produced a biphasic inotropic response which was composed of an early small decline and subsequent increase in force of contraction. In the presence of the Al3+ chelator, deferoxamine (100 microM), the positive inotropic response was completely abolished and a sustained negative inotropic response appeared, suggesting that only the positive inotropic response is due to the action of fluoroaluminates. 3. The positive inotropic effect of fluoroaluminates was associated with a significant increase in the total duration of a single contraction; the time to peak tension and relaxation time were prolonged. In contrast, these parameters were substantially abbreviated by isoprenaline or histamine. 4. When force of contraction was increased by isoprenaline or histamine, the addition of fluoroaluminates caused a marked negative inotropic effect, which was eliminated by pretreatment with pertussis toxin. 5. Fluoroaluminates did not cause a significant increase in cyclic AMP content at concentrations of NaF in the range of 1-10 mM. However, the content of cyclic AMP was greatly elevated by fluoroaluminates when the atrial muscles were pretreated with pertussis toxin. 6. Accumulation of [3H]-inositol monophosphate in atrial muscle strips prelabelled with myo-[3H]-inositol was significantly increased by fluoroaluminates at concentrations of NaF over 1 mM. The phosphoinositide response to fluoroaluminates remained unchanged with pertussis toxin pretreatment. 7.These results indicate that, in rabbit left atrial muscles, fluoroaluminates produce a positive inotropic effect which may be mediated by Gq but not by Gs proteins; they produce a negative inotropic effect possibly through Gi only when Gs is activated with other agents.
Aluminum↗
Thapsigargin- and cyclopiazonic acid-induced endothelium-dependent hyperpolarization in rat mesenteric artery.
1. The present study was designed to determine whether putative, selective inhibitors of the Ca(2+)-pump ATPase of endoplasmic reticulum, thapsigargin (TSG) and cyclopiazonic acid (CPA), induce endothelium-dependent hyperpolarization in the rat isolated mesenteric artery. The membrane potentials of smooth muscle cells of main superior mesenteric arteries were measured by the microelectrode technique. 2. In tissues with endothelium, TSG (10(-8)-10(-5) M) caused sustained hyperpolarization in a concentration-dependent manner. In tissues without endothelium, TSG did not cause any change in membrane potential. CPA (10(-5) M) also hyperpolarized the smooth muscle membrane, an effect that was endothelium-dependent and long-lasting. 3. The hyperpolarizing responses to these agents were not affected by indomethacin or NG-nitro-L-arginine (L-NOARG). 4. In Ca(2+)-free medium, neither TSG nor CPA elicited hyperpolarization, in contrast to acetylcholine which generated a transient hyperpolarizing response. 5. In rings of mesenteric artery precontracted with phenylephrine, TSG and CPA produced endothelium-dependent relaxations. L-NOARG significantly inhibited the relaxations to these agents, but about 40-60% of the total relaxation was resistant to L-NOARG. The L-NOARG-resistant relaxations were abolished by potassium depolarization. 6. These results indicate that TSG and CPA can cause endothelium-dependent hyperpolarization in rat mesenteric artery possibly by releasing endothelium-derived hyperpolarizing factor and that membrane hyperpolarization can contribute to the endothelium-dependent relaxations to these agents. The mechanism of hyperpolarization may be related to increased Ca2+ influx into endothelial cells triggered by depletion of intracellular Ca2+ stores due to inhibition of endoplasmic reticulum Ca(2+)-pump ATPase activity.
Acetylcholine↗
Evidence for selective inhibition by lysophosphatidylcholine of acetylcholine-induced endothelium-dependent hyperpolarization and relaxation in rat mesenteric artery.
The effects of lysophosphatidylcholine (LPC) on acetylcholine-induced hyperpolarization and relaxation were examined in rat mesenteric arteries. LPC (3-10 microM) reversibly inhibited endothelium-dependent hyperpolarization by acetylcholine in a concentration-dependent manner. LPC (10 microM) inhibited only partially endothelium-dependent relaxation by acetylcholine. However, acetylcholine-induced relaxation obtained in the presence of 100 microM NG-nitro-L-arginine was almost completely eliminated by 10 microM LPC. These results indicate that LPC inhibits hyperpolarization and relaxation due to endothelium-derived hyperpolarizing factor more specifically than the relaxation due to endothelium-derived nitric oxide.
Acetylcholine↗
Voltage-dependence of Ca2+ agonist effect of YC-170 on cardiac L-type Ca2+ channels.
1. We investigated the voltage-dependence of the agonist actions of YC-170, a dihydropyridine (DHP) derivative, on cardiac L-type Ca2+ channels in rabbit ventricular cells, using the patch clamp technique. The characteristics of YC-170 were compared with those of other DHP Ca2+ agonists (Bay K 8644, CGP 28392). Ca2+ channel activities were elicited by depolarizing pulses to 0 mV from a holding potential (HP) of either -80 mV or -40 mV. 2. YC-170 (10 microM) increased Ca2+ channel activities when HP was set at -80 mV. However, decreasing HP to -40 mV abolished the agonist action. The agonist effect of Bay K 8644 (1 microM) on Ca2+ channels was elicited to the same extent at either HP. CGP 28392 (10 microM) also increased Ca2+ channel activities at both HPs, but its agonist effect was significantly larger at an HP of -80 mV than at -40 mV. 3. All of the three DHP Ca2+agonists prolonged open times of Ca2+ channels, but the prolongation did not correspond to the voltage-dependence of Ca2+ agonist effects of the three DHPs. 4. YC-170 markedly reduced the closed time of the Ca2+ channel when the HP was at -80 mV, but prolonged it at HP of -40 mV. Bay K 8644 reduced closed times at an HP of -80 mV. At an HP of -40 mV, Bay K 8644 slightly reduced closed times. CGP 28392 reduced closed times at an HP of -80 mV and prolonged those at an HP of -40 mV. Thus the voltage-dependence of the agonist effects of these agents was in good agreement with the voltage-dependence of changes in closed times of Ca2+ channel. 5. Two mechanisms may be involved in the agonist action of YC-170; a prolongation of open times, and a reduction of closed times of Ca2+ channels, i.e. an increase in reopening. The former mechanism is not dependent on Hp and the latter mechanism is highly dependent on HP. Thus, the voltage-dependence of the agonist action may be attributed to the voltage-dependence of their enhancing effect on reopening of Ca2+ channels.
3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
Regression of left ventricular hypertrophy prevents ischemia-induced lethal arrhythmias. Beneficial effect of angiotensin II blockade.
To evaluate the preventive effect of regression of left ventricular hypertrophy (LVH) on sudden cardiac death (SCD), the incidence of ventricular tachycardia or ventricular fibrillation (VT/Vf) after left coronary artery occlusion in Langendorff preparations was studied in the following five groups: (1) spontaneously hypertensive rats (SHR) without treatment (SHR-N), (2) SHR treated with captopril (SHR-C), (3) SHR treated with the angiotensin II receptor antagonist TCV-116 (SHR-A), (4) SHR treated with hydralazine (SHR-H), and (5) Wistar-Kyoto (WKY) rats. Although blood pressure was equally lowered in all treated groups, SHR-C and SHR-A but not SHR-H showed regression of LVH. The incidence of VT/Vf was 5% in WKY rats, 63% in SHR-N (P < .005 versus WKY rats), 0% in SHR-C, 10% in SHR-A, and 45% in SHR-H (P < .05 versus WKY rats). Further evaluation of the effect of TCV-116 revealed that SHR treated with a low dose of TCV-116 (1 mg/kg per day) showed a decrease in left ventricular mass with only a little decrease in blood pressure and that the incidence of VT/Vf was reduced in association with the degree of regression of LVH. Electrophysiological study using microelectrode techniques revealed that in the LVH groups (SHR-N and SHR-H), the action potential duration (APD) of the left ventricular papillary muscle was more prolonged than in WKY rats, whereas APD shortened to a greater extent during superfusion with a hypoxia/no-glucose solution. APD showed no difference in the regression groups (SHR-C and SHR-A) compared with the WKY group.(ABSTRACT TRUNCATED AT 250 WORDS)
Angiotensin II↗