Biomedical subjects
Publications and source records attributed to M Sakakibara.
The absolute stereochemistry of yeast reduction products 2s and 2a from 2-(3',4'-dimethoxy-cinnamyl)-2-methylcyclopentane-1,3-dione (1) was investigated. The results from several spectral studies and chemical correlations enabled their absolute configurations to be concluded as (2S,3S) and (2R,3S), respectively.
OBJECTIVES: To investigate changes in postprandial electrogastrography (EGG) from the neurohormonal mechanisms. METHODS: We measured EGG indices [frequency amplitude of normal 3-cpm (EGG-3 cpm)], high frequency amplitude of heart rate variability which has reflected cardiac parasympathetic tone, and several serum immunoreactive (ir)-hormone levels in 12 fasted male volunteers (mean age 25.3 yr). RESULTS: Immediately after the liquid food intake (250 kcal), a transient decrease in EGG-3 cpm frequency (from 0.045 +/- 0.001 Hz to 0.040 +/- 0.001 Hz; p < 0.05) accompanied by an increase in high frequency amplitude (from 31.05 +/- 3.45 ms to 39.10 +/- 4.08 ms; p < 0.05), and a serum immunoreactive gastrin level increase (from 38.72 +/- 4.92 pmol/L to 54.00 +/- 10.45 pmol/L; p < 0.05) and an immunoreactive somatostatin level decrease (from 15.00 +/- 0.43 pmol/L to 13.70 +/- 0.46 pmol/L; p < 0.01) were observed, suggesting vagal excitement. EGG-3 cpm amplitude and serum immunoreactive human pancreatic polypeptide (hPP) levels significantly increased soon after ingestion, and these changes lasted for 30 min. Furthermore, there was a positive correlation between changes in EGG-3 cpm amplitude and those in serum immunoreactive hPP levels during the postprandial periods (r = 0.55, p < 0.001). CONCLUSIONS: Considering the reports that a cholinergic, nonvagal pathway is of major importance in food-stimulated hPP release, the present results suggest that postprandial changes in EGG-3 cpm frequency and amplitude might be a good tool for evaluating not only vagal but also nonvagal cholinergic activity in the human gut.
Diesel engine-powered vehicles emit some 30 to 100 times more particles than do gasoline engine cars. We previously reported that diesel exhaust particles (DEP) instilled intratracheally into mouse caused lung edema accompanying endothelial cell damage. In order to clarify further the biological effects of DEP on the respiratory system, the primary target of DEP instillation, we examined the direct action of DEP on isolated tissues and the cytotoxicity of DEP on cultured cells of respiratory tracts in guinea pigs. DEP were collected on glass fiber filters from a light-duty (2730 cc), four cylinder diesel engine. DEP induced a dose-dependent relaxation in tracheal smooth muscle and lung parenchymal preparations from guinea pigs. Neither propranolol nor ranitidine inhibited the relaxing effect of DEP on tracheal preparations. DEP also exhibited concentration- and time-dependent cytotoxicity on cultured tracheal smooth muscle cells and lung fibroblasts from guinea pigs, as assessed by specific [51Cr] release. These cytotoxicities induced by DEP were significantly inhibited by catalase, deferoxamine and MK-447, whereas SOD and mannitol had little effect. These inhibitory effects were blunted by the higher concentration of DEP. These results suggest that the cytotoxicity of DEP may cause dysfunction of respiratory tissues, which are mediated via oxygen radicals, probably hydroxyl radicals or hydrogen peroxides.
Direct evidence that the photoresponse of the Hermissenda type B photoreceptor cell is triggered directly by the hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2) was obtained. Neomycin and spermine, which inhibit PIP2 breakdown, suppressed light response, while injection of inositol 1,4,5-trisphosphate (IP3), guanosine 5'-(3-O-thio)triphosphate (GTP gamma S), guanosine 5'-(2-O-thio)diphosphate (GDP beta S), cAMP, cGMP did not alter the light-induced Na+ influx underlying the photoresponse. Suppression of the photoresponse was also observed with decrease of total amount of membraneous PIP2 induced by injection of the phosphoinositides (PI) turnover inhibitors, isobutylmethylxanthine (IBMX), LiCl and R 59022.
Two carp of 26 cm in size, intact and otolith-removed (LB), were flown on the Spacelab-J for 8 days in September 12-20, 1992. Light-dependent reaction to alternating direction of illumination was recorded for 10 min twice a day together with the cerebellar EEG activity, on 2 days before the launch, during the flight and for 4 days after the landing, in same fish chamber. Reproducing the video image, it was revealed that both carp were healthy during the mission, but the LB fish was almost immobilized from the 3rd test session (48 hours in flight) by tight twisting of the EEG cable. Both fish after landing tended to stay still on the bottom of the fish chamber. Findings that the body weight reduced remarkably in both fish and that nitrite and nitrate levels of the fish water were usually high, suggested that the fish metabolism might have been enhanced during the flight.
To examine the hypothesis that the relaxation response is associated with an increase in cardiac parasympathetic tone, the frequency components of heart rate variability during relaxation training were investigated in 16 college students. Electrocardiograms and pneumograms were recorded during a 5-min baseline period followed by three successive 5-min sessions of the autogenic training (relaxation) or by the same periods of quiet rest (control), while subjects breathed synchronously with a visual pacemaker (0.25 Hz). Although neither the magnitude nor the frequency of respiration showed a significant difference between relaxation and control, the amplitude of the high-frequency component of heart rate variability increased only during relaxation (p = .008). There was no significant difference in the ratio of the low-frequency (0.04-0.15 Hz) to the high-frequency amplitudes. The increased high-frequency amplitude without changes in the respiratory parameters indicates enhanced cardiac parasympathetic tone. Thus, our results support the initial hypothesis of this study. Enhanced cardiac parasympathetic tone may explain an important mechanism underlying the beneficial effect of the relaxation response.
To determine whether paced breathing (PB) and respiratory interval of PB modify the relationship between spectral components of heart rate variability (HRV) and cardiac vagal tone, we studied seven healthy young males under the condition of beta-adrenergic blockade by intravenous propranolol (0.2 mg/kg). Compared with spontaneous breathing, PB at the same respiratory interval as that of individual spontaneous breathing showed no significant effect on the amplitude of the high-frequency (HF) component or the mean R-R interval in either the supine or tilt position, whereas the PB decreased the amplitude of the low-frequency (LF; 0.04-0.15 Hz) component in both positions (P = 0.004 and 0.042, respectively). When the respiratory interval was increased from 3 to 6 s, the HF amplitude showed a progressive increase in both positions (P = 0.001 and 0.035, respectively), while the LF amplitude and mean R-R interval remained unchanged. These results indicate that the effects of PB and respiratory interval on the spectral components of HRV are not mediated by the changes in mean cardiac vagal tone and support the hypothesis that increased respiratory interval amplifies the respiratory-related vagal modulation of heart rate.
Diesel engine-powered vehicles emit some 30 to 100 times more particles than do gasoline engine cars. We previously reported that diesel exhaust particles (DEP) could produce superoxide anions in an in vitro study. Furthermore, mice instilled intratracheally with DEP showed high mortality at low doses. The cause of death was lung edema with damage to the lung endothelial cells. In order to elucidate the mechanism of the onset of mortality induced by DEP, we examined the direct action of DEP on the isolated atrium of guinea pigs. A light-duty (2740cc), four cylinder diesel engine was used. The DEP were collected on fiberglass filter. DEP caused a negative inotropic action that was followed by the cardiac arrest of the isolated left atrium. These actions were not inhibited by propranolol, atropine, verapamil, diltiazem, diphenhydramine, indomethacin, superoxide dismutase or catalase. The precise mechanism of cardiac arrest is unknown. However, these results suggest that cardiac toxicity induced by DEP might be involved in lung edema.
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Two adenocarcinoma cell lines were established from metastatic lymph node of lung cancer patients. The cell lines were named NUTLC-1 and NUTLC-3. They were found to have the following biological characterization and sensitivity to anticancer agents by comparison with clinical effect of the drugs on each donor patient: 1) By chromosomal analysis, the tumor cells of two cell lines were human-origin cells. Number of chromosomes of these cell lines ranged from 67 to 77 in NUTLC-1 cells and from 61 to 66 in NUTLC-3 cells, with the modal numbers of 73 and 64, respectively. 2) The tumor cells of the two cell lines were heterotransplanted subcutaneously into nude mice, but, no natural distant metastasis was observed 2 months after transplantation. 3) Sensitivity to anticancer agents on NUTLC-1 and NUTLC-3 cells differed individually according to methylthiazol tetrazorium (bromide) (MTT) colorimetric assay. NUTLC-1 cells were sensitive to Mitomycin C (MMC) and Adriamycin (ADM), and insensitive to Cisplatinum (CDDP), 5-Fluorouracil (5-FU) and Etoposide (VP-16). Antitumor effect of CDDP and 5-FU on recurrent tumor of donor patient was not observed clinically. NUTLC-3 cells were sensitive to CDDP, MMC and ADM, and insensitive to 5-FU and VP-16. Sensitivity to CDDP and MMC on NUTLC-3 cells also correlated to clinical effect of the drugs on the donor patient. From these results, it appears that these new cell lines are useful materials for studies on lung cancer.
Previous observations have implicated GABA as a neurotransmitter released by the vestibular sensory neurons ("hair cells") of the snail Hermissenda onto visual sensory neurons, the type B cells, whose cell bodies are the sites of biophysical and biochemical changes during and following Pavlovian conditioning. Still other observations demonstrated that light-GABA pairings that simulate stimuli presented during Pavlovian conditioning cause prolonged elevation of intracellular Ca2+ and transformation of GABA-induced synaptic inhibition into excitation. Intracellular Ca2+ signals in response to GABA perfused onto the postsynaptic type B terminal branches are shown here to be prolonged on days after conditioning, but not after control paradigms. These and past results demonstrate two separate sites, i.e., the cell body and the terminal branches, for learning-induced changes after Pavlovian conditioning.
The distribution and localization of Helicobacter pylori (HP) and mononuclear cells (MNC) in the gastric mucosa were investigated immunohistochemically in 120 patients with gastritis or peptic ulcer. HP was detected in the gastric mucosa of 58% of 40 gastritis patients, 82% of 56 gastric ulcer (GU) patients, and 88% of 24 duodenal ulcer (DU) patients. In the HP-positive mucosa, cells positive for IgG or IgA were increased significantly when compared to the HP-negative mucosa. Neutrophils and eosinophils were also increased under the HP-infected surface and therefore these cells were likely involved in the mucosal damage. Enhancement of the expression of HLA-DR antigen was observed in the gastric epithelium with HP infection and it was associated with a significant increase of lymphoid follicles and B cells in the mucosa. In comparison with the HP-infected mucosa of gastritis patients, the number of MNC were increased significantly in the mucosa of both DU and GU patients. The number of HP in the gastric mucosa of DU patients was significantly higher than those of both gastritis and GU patients. In addition, the grade of the infiltration of MNC and IgA positive cells were always greater in DU than in gastritis, regardless of the number of HP. These findings suggested that activation of the local immunity in the gastric mucosa of gastritis and peptic ulcer patients by HP infection may participate in the pathogenesis of gastroduodenal mucosa damage.
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An endogenous Na-pump specific inhibitor has been purified to homogeneity from normal pig urine using Amberlite XAD-2 adsorption chromatography followed by five steps of reverse phase HPLC. Although most of the dose response curves for this purified Na-pump inhibitor, designated uroxin, in the various assay systems paralleled those of authentic ouabain and the specific Na-pump inhibitor previously purified from bovine adrenal glands (designated adrexin C), the cross-reactivity curve with anti-ouabain antibodies did not. The retention times of uroxin on various types of reverse phase HPLC columns were also different from those of plant-derived cardiotonic steroids and adrexin C. The cross-reaction curve of adrexin C was superimposable with that of ouabain, and adrexin C coeluted with ouabain from all of the HPLC columns tested. The results from physical and chemical characterization of both purified inhibitors suggest that uroxin is a novel Na-pump inhibitor which is structurally different from any of the known cardiotonic steroids or other substances previously reported to exhibit Na-pump inhibitory activity. The results also indicate that adrexin C is indistinguishable from ouabain. These results suggest that there are at least two different types of endogenous Na+,K(+)-ATPase inhibitors in the mammalian body.
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Movements of medium and large sized membranous organelles (0.5-1 microns in diameter) were visualized within segments of the crab walking leg nerve with Nomarski differential interference contrast optics and subjected to video contrast enhancement. Accessibility to the axoplasm was demonstrated by intra-axonal fluorescence following addition of rhodamine conjugated to 40 kDa dextran to the external medium. Perfusion of the axons with a 1 microM solution of the 20 kDa G-protein, cp20, but not control solutions, reduced the number of organelles moving in the retrograde direction per unit time, but not the number of organelles moving in the anterograde direction. Such alteration of organelle movement may contribute to memory-specific changes of neuronal morphology.