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Biomedical subjects

M Sakakibara

Publications and source records attributed to M Sakakibara.

At least 55 records · Page 3Linked to original sources

Sensory preconditioning for feeding response in the pond snail, Lymnaea stagnalis.

We demonstrated a sensory preconditioning in the pond snail, Lymnaea stagnalis. An appetitive sucrose solution (a conditioned stimulus: CS1) and weak vibration (another conditioned stimulus: CS2) were first associated, and then the CS2 and an aversive KCl solution (an unconditioned stimulus: UCS) were done. To build the conditioning, two different training procedures, spaced and massed, were examined. After the both training, the sensory preconditioning was built: significantly fewer feeding response to the CS1 became elicited; slower latency to the first bite to the CS1 was induced. No significant differences on the memory retention between these training procedures were found in the sensory preconditioning.

Animals↗

Immunohistochemical demonstration of carcinogen-DNA adducts in tissues of rats given 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP): detection in paraffin-embedded sections and tissue distribution.

A polyclonal antibody against 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)-DNA adducts was raised for their immunohistochemical demonstration in paraffin-embedded sections. Specificity of this antibody was confirmed by competitive ELISA. Positive signals were immunohistochemically detected in acetone-fixed but not in formalin- or ethanol-fixed sections from F344 rats treated by gavage with a single dose of PhIP at 37.5-300 mg/kg and killed at 1, 2, and 7 days thereafter. Dose-dependent positive staining was observed in almost all organs of both sexes, including the colon, prostate, and mammary gland but largely independent of the tumor response. Repair activity, judged by disappearance of adducts with time, differed according to the organ or cell type. One exception was hepatocytes, the liver incidentally being a nontarget organ. The results suggest that the generated antibody is applicable for detection of cells targeted by PhIP in paraffin-embedded sections and also for the investigation of the mechanisms of PhIP-carcinogenesis.

Administration, Oral↗

Evidence for the involvement of inositol trisphosphate but not cyclic nucleotides in visual transduction in Hermissenda eye.

Although several second messengers are known to be involved in invertebrate photoresponses, the mechanism underlying invertebrate phototransduction remains unclear. In the present study, brief injection of inositol trisphosphate into Hermissenda photoreceptors induced a transient Na+ current followed by burst activity, which accurately reproduced the native photoresponse. Injection of Ca2+ did not induce a significant change in the membrane potential but potentiated the native photoresponse. Injection of a Ca2+ chelator decreased the response amplitude and increased the response latency. Injection of cGMP induced a Ca2+-dependent, transient depolarization with a short latency. cAMP injection evoked Na+-dependent action potentials without a rise in membrane potential. Taken together, these results suggest that phototransduction in Hermissenda is mediated by Na+ channels that are directly activated by inositol trisphosphate without mobilization of cytosolic Ca2+.

Animals↗

Relationship between CD44 expression and differentiation of human prostate adenocarcinomas.

It is well documented that CD44 plays an important role in tumor metastasis. We investigated whether there is a correlation between the expression of its isoforms in prostate cancer cells and patient prognosis using 72 cases with biopsy specimens. Immunohistochemistry demonstrated expression of CD44H (68.1%), v6 (36.1%) and v9 (68.1%) to be relatively more frequent than that of other isoforms. A positive correlation between CD44H expression and tumor differentiation was found but this did not extend to clinical staging or prognosis. Likewise, results for CD44v6 or v9 expression suggest that they may be useful markers for prostate adenocarcinoma differentiation but not prognosis.

Adenocarcinoma↗

Associative learning of visual and vestibular stimuli in Lymnaea.

A conditioned withdrawal response was characterized in the pond snail Lymnaea stagnalis. Using light as the conditioned stimulus and high-speed orbital rotation as the unconditioned stimulus, experimental animals were trained with 30 paired presentations of light and orbital rotation per day for 3 days. After training, all experimental animals responded to light with a withdrawal response, the conditioned response. Control animals exposed to the same number of explicitly unpaired presentations of light and orbital rotation, light alone, or no stimulation did not respond to light. Thirty paired presentations per day for 2 days produced less than optimal acquisition of the conditioned withdrawal response. Neither 45 paired presentations per day for 2 days nor 90 paired presentations for 1 day resulted in complete acquisition of the conditioned withdrawal response. The conditioned withdrawal response observed following 30 paired presentations per day for 3 to 5 days persisted to Day 10, regardless of the number of training days. As a measure of savings, reacquisition of the conditioned response after extinction was investigated. After the conditioned withdrawal response was extinguished, only 2 to 5 paired presentations of light and orbital rotation were required for reacquisition of the conditioned response for most animals. This study further establishes Lymnaea as an animal model of basic associative learning.

Animals↗

Beneficial effects of mechanical reperfusion therapy on left ventricular remodeling and late outcome following myocardial infarction.

The long-term relative benefits of thrombolysis and mechanical reperfusion therapy following acute myocardial infarction (AMI) have not been established. The purpose of this study was to compare left ventricular function, left ventricular remodeling and late outcome after AMI for different reperfusion therapies. Thirty consecutive patients suffering their first anterior wall myocardial infarction with coronary stenoses limited to the left anterior descending coronary artery were studied. They included 10 patients who underwent intracoronary thrombolysis (ICT), 10 who underwent PTCA and 10 who underwent noninterventional medical treatment. All patients underwent coronary angiography (CAG) during the acute phase of AMI and also during the follow-up period, and left ventriculography during the follow-up period and clinical follow-up was performed (mean clinical follow-up period: 53 +/- 31 months). No significant difference in global ejection fraction was noted among the groups, although the end-diastolic volume index (EDVI) in the PTCA group (79.4 +/- 17.5 ml/m2) was significantly smaller than in the noninterventional (106.1 +/- 25.1 ml/m2) and ICT (107.9 +/- 28.3 ml/m2) group (p < 0.05). The regional wall motion index (RWMI) for the anterior region in the PTCA group (-2.7 +/- 0.8) was greater (p < 0.05) than in the noninterventional (-3.4 +/- 0.6) and ICT (-3.3 +/- 0.6) groups. A significant linear correlation was found between EDVI and % diameter stenosis and also between RWMI and % diameter stenosis following reperfusion (p = 0.01). There was no difference in the incidence of cardiac death, nonfatal reinfarction, bypass surgery or congestive heart failure among the groups. Disturbed left ventricular regional wall motion and remodeling benefit most from angioplasty because of prompt restoration of adequate blood flow. However, there was no difference in late outcomes following AMI among the three groups.

Adult↗

[Assessment of localized hypertrophy in the basal part of the interventricular septum in the elderly].

The basal part of the interventricular septum (IVS) is known to show different hypertrophic features from those observed in the other parts of the left ventricular wall. These are considered to reflect physiological changes that occur with normal aging. However, these changes have not been carefully evaluated, and their clinical significance has not been defined. We assessed these changes echocardiographically. The subjects were patients at least 70 years of age in whom localized hypertrophy in the basal part of the IVS was seen during the whole cardiac cycle on echocardiography. The prevalence was 6.3% among 96 consecutively studied patients. All 6 patients had a history of hypertension. Echocardiographic findings were as follows: 1) the left atrium was mildly or moderately dilated, 2) there was no evidence of either dilatation or narrowing of the left ventricular cavity, 3) the left ventricular wall motion appeared normal and indices of systolic function were within normal limits in all subjects except one who had a history of myocardial infarction, 4) the angle formed by the aorta and the IVS averaged 106.7 degrees (range: 95 to 120 degrees), 5) Doppler examination showed increases in the ratio of the peak flow velocity during atrial systole to the peak flow velocity early in diastole, and 6) prolongation of the deceleration time of the flow velocity early in diastole. The last of these findings suggested left ventricular diastolic dysfunction, but peak flow velocity at the left ventricular outflow tract was normal. There was no evidence of stenosis of the left ventricular outflow tract. Localized hypertrophy in the basal part of the IVS in elderly patients could be a type of cardiac hypertrophy caused by hypertension. On echocardiography, the basal part of the IVS seemed to protrude toward the left ventricular cavity, but there was no evidence of stenosis in the left ventricular outflow tract.

Aged↗

[Drug delivery system in cardiovascular drugs].

Various drug delivery systems are available when cardiovascular drugs are used. Various kinds of receptor inhibitors such as beta blockade or angiotensin II receptor inhibitor are frequently used in the daily cardiovascular clinic. Several different routes of drug administration exist. Conventional tablet or its liquid spray by sublingual or lingual administration is rapidly absorbed and specified oral tablet or transdermal patch for maintaining longtime is slowly absorbed from the digestive tract or skin. Some drugs have different type of tablets for obtaining different pharmacodynamics. Nifedipine has 3 kinds of tablets showing short, long and very long-time effect. Recent advance in drug delivery system makes possible to administer the drug to the small local area through stent or balloon catheter at the coronary interventional therapy.

Angioplasty, Balloon, Coronary↗

Lactose hydrolysis and beta-galactosidase activity in sonicated fermentation with Lactobacillus strains.

Milk fermentation with four Lactobacillus strains, including L. delbrueckii subsp. bulgaricus B-5b, L. helveticus LH-17, L. delbrueckii subsp. lactis SBT-2080 and L. acidophilus SBT-2068, was carried out under sonicated conditions. Under continuous sonication, viable cell count decreased or grew less than in conventional fermentation, but it increased considerably in static incubation after sonication. Sonication caused beta-galactosidase release from lactic acid bacteria cells to the culture medium, thus resulting in higher total beta-galactosidase activity. However, lactose hydrolysis was enhanced only when beta-alactosidase was effectively released. With L. delbrueckii subsp. bulgaricus B-5b and L. helveticus LH-17. the degrees of lactose hydrolysis achieved were about 75% which is much higher than those in conventional fermentation (below 40%). Results presented here showed that a high viable cell count and a high degree of lactose hydrolysis could be simultaneously achieved by a suitable sonication method.

Culture Media↗

[Successful direct percutaneous transluminal coronary angioplasty in a 91-year-old male with acute myocardial infarction complicating cardiogenic shock].

A 91-year-old male patient was admitted to hospital with acute myocardial infarction complicating cardiogenic shock. An emergency coronary arteriogram showed 99% stenosis at the mid-section of the right coronary artery, and in order to achieve an early recovery direct percutaneous transluminal angioplasty (PTCA) was performed through the brachial artery using a 6 french catheter. The lesion was successfully dilated up to 25% residual stenosis. Hypointention had been sustained during the admission; however, it gradually improved and he was discharged on the 31st hospital day. He has been followed up for 6 months after discharge at the out-patient clinic and has not recurrent ischemic episodes. According to other reports on the use of direct PTCA in the elderly, the postdischarge mortality rate is lower than that with medical therapy or thrombolysis. When cardiogenic shock occurs even in the elderly, direct PTCA should be selected as the first choice of treatment.

Aged↗

Tenidap, a structurally novel drug for the treatment of arthritis: antiinflammatory and analgesic properties.

Tenidap is a new anti-rheumatic agent which has clinical properties characteristic of a disease modifying drug combined with acute antiinflammatory and analgesic activity. This paper details tenidap's cyclooxygenase (COX) inhibitory activity and the resulting pharmacological properties in experimental animals. Tenidap inhibited calcium ionophore-stimulated prostaglandin D2 synthesis by rat basophilic leukemia cells (COX-1) with an IC50 of 20 nM. In two different in vitro human test systems, tenidap inhibited COX-1 activity more potently than COX-2, although the relative potency ratio (COX-1/COX-2) differed markedly between the two systems. Tenidap inhibited the COX pathway when added to human blood in vitro (IC50, 7.8 mu M) and when administered orally to monkeys, rats and dogs (at 5, 2.5 and 10 mg/kg p.o., respectively) and COX activity measured ex vivo in blood collected 2 to 4 hours post dose. After oral administration to rats, tenidap inhibited carrageenan-induced paw edema with an ED50 of 14 mg/kg and inhibited the glucocorticoid-resistant UV erythema in guinea pigs with an ED50 of 1.4 mg/kg. It retained antiinflammatory activity in adrenalectomized rats indicating that this property is independent of adrenal stimulation. Oral administration of tenidap inhibited the development of adjuvant-induced polyarthritis in the rat and exhibited antinociceptive activity in the murine phenylbenzoquinone and rat acetic acid abdominal constriction tests. These data indicate that tenidap is an effective antiinflammatory and analgesic agent in animal models. These cyclooxygenase-dependent pharmacologic activities do not explain tenidap's disease modifying anti-arthritic properties but add a useful symptom modifying component to its clinical profile.

Analgesics, Non-Narcotic↗

Effects of cilazapril on exercise tolerance in the chronic phase of acute myocardial infarction.

The present study was conducted to investigate the effects of cilazapril on exercise tolerance and the hormone kinetics of catecholamines, the reninangiotensin-aldosterone system and alpha-atrial natriuretic peptide (ANP) in patients in the chronic phase of acute myocardial infarction (AMI). The subjects consisted of 19 cases of AMI. Cardiopulmonary exercise testing was performed 1 month after the onset of AMI, and patients were randomly assigned to either a group treated with 1 mg/day of cilazapril (9 cases) and or an untreated group (10 cases). After the completion of 2 months of exercise training at the anaerobic threshold (AT), blood samples were taken during a cardiopulmonary exercise test and various hormones were measured. In comparing the parameters of exercise tolerance before and after the completion of exercise training there were no significant differences between the 2 groups with respect to oxygen uptake, oxygen pulse, or exercise time at AT or at peak exercise. With regard to temporal changes in exercise tolerance, oxygen uptake, oxygen pulse and exercise time all tended to increase in both groups. With regard to hormone kinetics, the alpha-ANP concentration at peak exercise was significantly lower, and the noradrenaline secretions also tended to be lower, in the cilazapril-treated group, even though the peak exercise time was similar in both groups. These results may be support the hypothesis that cilazapril mitigates the left ventricular load during exercise therapy in patients in the chronic phase of AMI.

Aldosterone↗

Syntheses of (14 beta,15 beta,16 beta,17 alpha)- and (14 beta,15 alpha,16 alpha,17 alpha)-1,3,5(10)-estratriene-2,3,14,15,16,17- hexaols, possible candidates for the Inagami--Tamura endogenous digitalis-like factor, and their activity.

Structures are proposed for the Inagami-Tamura endogenous digitalis-like factor (EDLF), and two possible candidates, (14 beta,15 beta,16 beta,17 alpha)- and (14 beta,15 alpha,16 alpha,17 alpha)-2,3,14,15,16,17-hexahydroxy-1,3,5(10)-estratrienes, were synthesized. Both compounds were potent in inducing a contractile response in isolated rat aorta and guinea pig left atrium.

Animals↗

Studies on cochleamycins, novel antitumor antibiotics. III. Biosyntheses of cochleamycins: incorporation of 13C- and 2H-labeled compounds into cochleamycins.

Biosynthetic studies using 13C- and 2H-labeled compounds revealed that the carbon skeletons of cochleamycins A and B were derived from eight acetic acid units and one propionic acid unit with the introduction of an acetoxy group at C-10, which was replaced by an isobutyryl residue derived from valine in cochleamycins A2 and B2.

Antibiotics, Antineoplastic↗

Interleukin-8 activity correlates with histological severity in Helicobacter pylori-associated antral gastritis.

OBJECTIVES: To examine the background histology, interleukin-8 (IL-8) secretion, and expression of IL-8 mRNA and protein, using the gastric antral mucosa infected with Helicobacter pylori. METHODS: The antral biopsies were obtained from an area of endoscopically intact mucosa in 147 patients whose endoscopic diagnoses were normal (n = 41), duodenal ulcer (n = 58), gastric ulcer (n = 21), or gastritis (n = 27). Levels of IL-8 secreted in the organ cultures of mucosal biopsies were measured by an ELISA assay, and the expression of IL-8 mRNA and protein was analyzed in fresh biopsy tissues with RT-PCR and immunofluorescent microscopy, respectively. RESULTS: Significantly greater levels of IL-8 were secreted in patients with H. pylori infection, and its elevation was more prominent in duodenal ulcer patients than in those with gastric ulcer or endoscopically defined gastritis. There was an association among H. pylori density, IL-8 activity, and histological severity of activity and inflammation of gastritis in the Sydney system. Consistent with enhanced IL-8 activity in the organ cultures, IL-8 mRNA was detected in 16 of 23 fresh biopsy tissues studied in H. pylori-positive patients. In contrast, IL-8 transcript was detected in only one of 12 H. pylori-negative cases. Immunofluorescent microscopy showed localization of IL-8 protein in the gastric epithelial cells and lamina propria cells, primarily CD68+ macrophages in specimens with H. pylori infection. CONCLUSIONS: This study indicates that a strong correlation exists between mucosal IL-8 activity and histological severity in H. pylori-associated antral gastritis. Further studies will be necessary to determine the mechanisms involved in elevated mucosal IL-8 activity in H. pylori infection.

Adult↗

Evidence of sensory conflict and recovery in carp exposed to prolonged weightlessness.

BACKGROUND: Evidence in support of the sensory conflict hypothesis for space motion sickness (SMS) is still needed. HYPOTHESIS: We hypothesized that sensory conflict and recovery processes should be demonstrated in intact fish during initial days of microgravity exposure, as a disturbance and restoration of the dorsal light response (DLR; a functional model of visual-graviceptor interaction), respectively. We also expected that this would be true in an otolith-removed fish if it had been fully compensated for dysfunction before the exposure. METHODS: The DLR of carp (Cyprinus carpio) was examined intermittently during the 8-d mission of Spacelab-J. Two carp, normal and labyrinthectomized (LB), made the flight. RESULTS: In the normal carp, the DLR was unstable for the first 3 d inflight but gradually recovered thereafter. The recovery was characterized by gradual restoration of the DLR tilt speed. The LB fish whose otoliths had been removed 2 mo before the flight maintained DLR at the first inflight test session (22 h after launch), but DLR was disrupted at 2 d as in normal fish. The recovery process could not be evaluated in this fish, because the EEG cable which was attached to the fish for supplementary study became tightly twisted and thus immobilized the fish for the remainder of the experiment. CONCLUSION: These findings provided additional evidence in fish for sensory-motor disorder and readjustment during the early phase of microgravity, thus supporting the sensory conflict hypothesis for SMS.

Animals↗