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Biomedical subjects

M Kawamoto

Publications and source records attributed to M Kawamoto.

At least 127 records · Page 7Linked to original sources

Staphylococcus aureus Wood 46 strain activates human B cells without affecting DNA synthesis or tyrosine phosphorylation.

Induction of Ig secretion in human tonsilar B cell by protein A-deficient Staphylococcus aureus WOOD 46 strain (SAW) was examined. SAW induced as much Ig secretion as protein A-rich S. aureus Cowan I strain (SAC) when IL-2 was present in the culture. Activated and resting B cells are separated by Percoll gradient to determine whether SAW stimulates either resting or activated B cells. In resting B cells, SAW plus IL-2 induced IgM secretion significantly, but neither IL-2 nor SAW alone induced IgM secretion. In activated B cells, however, IL-2 induced IgM secretion by itself and SAW plus IL-2 did not induce additional IgM secretion. These results suggest that SAW activates small resting B cells rather than preactivated B cells. Subsequently, mechanisms of B cell activation by SAW and SAC were compared. SAW did not induce [3H]-TdR incorporation through day 1 to 5, and the number of viable cells was not increased by SAW stimulation. Moreover, SAW did not induce significant tyrosine phosphorylation at any concentration tested, when tyrosine phosphorylation of B cells was examined. However, SAC induced both [3H]-TdR incorporation and tyrosine phosphorylation of B cell efficiently. In further experiments, induction of IL-2R and IgM mRNA expressions were examined. SAW by itself induced IL-2R and IgM mRNA expressions without affecting expression of membrane-type IgM mRNA. These results show that SAW activates human B cells in quite a different manner from SAC by up-regulating the expression of secretory type IgM mRNA without affecting cell proliferation nor tyrosine phosphorylation, proposing a distinct B cell activation model from SAC.

B-Lymphocytes↗

Oxidative metabolism in the myocardium in normal subjects during dobutamine infusion.

To assess the biventricular response of the clearance rate of carbon-11 acetate as an index of myocardial oxidative metabolism to increase in work-load, dynamic positron emission tomography was performed at rest and during dobutamine infusion in 14 normal subjects. The clearance rate constant (Kmono) of the left ventricular (LV) myocardium increased during dobutamine infusion (0.112 +/- 0.020 min-1 vs 0.065 +/- 0.015 min-1 at rest) (P < 0.001) in proportion to the increase in the pressure-rate product. Kmono in the right ventricular (RV) myocardium also increased (0.080 +/- 0.018 min-1 vs 0.034 +/- 0.013 min-1 at rest) (P < 0.001), with an excellent correlation with the LV Kmono (r = 0.920). The fact that the increase in RV Kmono during dobutamine infusion was greater (158% +/- 81%) than that in LV Kmono (79% +/- 39%) (P < 0.005) indicates a greater increase in oxidative metabolism in the RV in response to inotropic stimulation in normal subjects.

Acetates↗

Assessment of myocardial fatty acid metabolism with positron emission tomography at rest and during dobutamine infusion in patients with coronary artery disease.

The myocardial clearance rate of C-11 palmitate as an index of fatty acid oxidation was assessed by means of positron emission tomography (PET) at rest and during dobutamine infusion in seven normal subjects and 10 patients with coronary artery disease. In the normal subjects the clearance half time was homogeneous in the left ventricle at rest and uniformly shortened during dobutamine infusion. In the myocardium at risk, clearance half time tends to be longer in the segments with an abnormal Q wave on ECG, exhibiting regional wall motion abnormality, and supplied by severely stenosed coronary arteries, particularly during dobutamine infusion. These data indicate that fatty acid oxidation may be decreased in infarcted myocardium and associated with regional asynergy. Such an abnormality was most striking in those with severe coronary stenosis during dobutamine infusion. We conclude that PET with the use of C-11 palmitate at rest and during dobutamine is a useful means of identifying impaired fatty acid oxidation and decreased metabolic reserve in patients with coronary artery disease.

Carbon Radioisotopes↗

Power spectral analysis of heart rate variability after spinal anaesthesia.

Power spectral analysis of heart rate (HR) variability is a useful tool with which to assess cardiac autonomic activity. The low frequency bands have been considered as both sympathetically and parasympathetically mediated components, while the high frequency bands have been assumed to be the parasympathetically mediated respiratory components. It has been anticipated that spinal anaesthesia to the thoracic level may modulate cardiac autonomic activity to reduce HR and arterial pressure by blocking cardiac sympathetic activity. In order to quantify the alterations in cardiac autonomic activity, we have analysed the power spectra of HR variability for 30 min after subarachnoid administration of hyperbaric amethocaine. Using 256-s R-R interval data obtained from continuously recorded ECG, low frequency (Lo: 0.04-0.15 Hz) and high frequency (Hi: 0.15-0.40 Hz) band widths were integrated and their serial alterations were computed by shifting subjected R-R intervals at 60-s intervals. After the subarachnoid injection, arterial pressure, HR and Lo decreased and Hi and the Hi:Lo ratio increased. These changes were observed within 15-20 min. Ventilatory frequency did not change throughout the study. These findings suggest that the decrease in HR and arterial pressure after subarachnoid administration of hyperbaric amethocaine reflect decreased sympathetic activity and increased parasympathetic activity in the cardiac autonomic nervous system.

Adult↗

Chemiluminescence immunoassay to detect anti-HTLV-I antibodies.

A fully automated chemiluminescence immunoassay was developed for the detection of antibodies to HTLV-I. We used partially purified viral antigens coated on small polystyrene beads together with acridinium ester-labeled anti-human immunoglobulin G mouse immunoglobulin G in this method. A good agreement was observed between our proposed method, the indirect immunofluorescence assay, the particle-agglutination test and the enzyme immunoassay. This new method, which is simple, sensitive, specific and rapid, should be useful for mass screening of anti-HTLV-I antibodies.

HTLV-I Antibodies↗

PAF increases capillary pressure but not vascular permeability in isolated blood-perfused canine lungs.

We determined the effects of platelet-activating factor (PAF) on pulmonary vascular resistance, lung weight, and microvascular permeability in isolated canine lungs perfused at constant pressure with autologous blood. PAF caused a dose-dependent increase in total pulmonary vascular resistance (Rt) and pulmonary capillary pressure assessed as double-occlusion pressure. PAF (33 micrograms; n = 7) caused a 10-fold increase in Rt and a decrease in precapillary-to-postcapillary vascular resistance ratio from 0.97 +/- 0.10 to 0.38 +/- 0.03, suggesting predominant pulmonary venoconstriction. Shortly after PAF, lung weight decreased transiently and then increased, reaching a plateau above baseline (112.5 +/- 1.6%) at 30 min. In lungs perfused in the antidromic direction from the pulmonary vein to the artery (n = 5), PAF (33 micrograms) produced marked precapillary vasoconstriction, consistent with pulmonary venoconstriction, and a remarkable and sustained decrease in lung weight below baseline by 30 min. Vascular permeability, measured 30 min after PAF using the capillary filtration coefficient and isogravimetric capillary pressure, did not change significantly from baseline. Thus we conclude that PAF produces lung weight gain by means of an increase in capillary pressure predominantly due to pulmonary venoconstriction without significant changes in vascular permeability in isolated blood-perfused canine lungs.

Animals↗

[Three-dimensional assessment of myocardial blood flow and glucose metabolism using oblique-angle tomograms and polar map displays of cardiac PET images].

To evaluate clinical value of three-dimensional assessment of cardiac PET image, oblique-angle tomograms and polar map displays were reconstructed from transaxial PET images using 18F-2-fluoro-2-deoxyglucose and 13N-ammonia in 19 patients with coronary artery disease. Short-axis and vertical long-axis images enabled to evaluate extent and severity of perfusion abnormality easily in the anterior and inferior regions which were tangential in the transaxial images. Using polar map displays, perfusion/metabolism mismatch may be more easily assessed. Thus, semiquantitative analysis of ischemic and infarcted myocardium may be permitted with PET studies.

Aged↗

[Quantitative assessment of improvement in perfusion after coronary bypass grafting: assessed by thallium-201 bull's eye subtraction polar map method].

To assess redistribution (RD) and improvement in regional perfusion after coronary bypass grafting (CABG) on thallium-201 SPECT images quantitatively, the Bull's eye subtraction polar (BS) map was created. BS map was created after subtraction of a normalized bull's eye polar map from another normalized polar map. The quantitative assessment on this map was compared to the visual qualitative analysis in 23 patients (115 segments) who received CABG. All of the improved segments after CABG showed > or = 15% on the BS map. On the other hand, 60% of the non improved segments showed < 10% on the BS map. Furthermore, 67% of the RD segments showing > or = 15% on the BS map before CABG improved in perfusion by > or = 15% on the BS map after CABG. On the BS map, an excellent correlation was observed between the extent of redistribution before CABG and the extent of improvement after CABG. Thus, BS map permits quantitative assessment of improvement in perfusion on T1 SPECT imaging, and this technique seems to be valuable for predicting improvement in perfusion after CABG.

Adult↗

Role of sympathetic nervous system in hypotension induced by platelet-activating factor in anesthetized dogs.

This experiment was designed to investigate whether platelet-activating factor (PAF)-induced hypotension in anesthetized dogs produces changes in sympathetic activity in the heart, kidney, liver, and adrenal gland in intact animals (n = 5) and in animals with complete systemic baroreceptor denervation (n = 5). Following intravenous injection of PAF (10 micrograms/kg) in animals with intact baroreceptors, systemic blood pressure fell significantly. However, sympathetic nerve activity in the kidney, liver, and adrenal gland revealed a biphasic pattern: an initial increase (within 30 sec) followed by a progressive reduction below the preinjection level. In contrast to these nerve responses to PAF, only cardiac nerve activity showed an initial and significant increase, and it remained elevated above the preinjection level until the end of the experiment (10 min). In animals with complete systemic baroreceptor denervation, these sympathetic responses to PAF did not differ significantly from the responses in the intact animals. These results indicate that intravenous injection of PAF produces differential control of sympathetic nerve activity in different organs. The contribution of systemic baroreceptors to reflex compensations is minor in PAF-induced hypotension.

Adrenal Glands↗

[Evaluation of coronary artery disease by 99mTc-PPN1011: comparison with 201Tl imaging and ventricular function].

To evaluate clinical value of 99mTc-1,2-bis[bis (2-ethoxyethyl)phosphino]ethane(99mTc-PPN1011) imaging for assessing coronary artery disease (CAD), 99mTc-PPN1011 SPECT imaging at post-exercise and at rest was compared with 201Tl SPECT imaging at post-exercise and 3 hours in 24 patients with CAD. The sensitivities for detecting CAD were 100% (21/21) by 99mTc-PPN1011 SPECT and 95% (20/21) by 201Tl SPECT. The sensitivities for detecting stenosed coronary arteries (> or = 75% stenosis) were similar between 99mTc-PPN1011 (68%) and 201Tl (66%). The similar specificity values were obtained by 99mTc-PPN1011 (80%) and 201Tl (77%). The patterns of abnormality (normal, ischemia and scar) were concordant between 99mTc-PPN1011 and 201Tl images in 20 of the 24 cases (83%) and 106 of the 120 segments (88%). In the simultaneous analysis of cardiac function by first pass radionuclide angiography with 99mTc-PPN1011, there was good correlation between left ventricular ejection fraction and perfusion score at rest (r = 0.70) and exercise (r = 0.80). The degrees of abnormality between perfusion and wall motion were similar in 56 of 66 segments (85%) at rest and 52 of 66 segments (79%) at exercise. We conclude that this agent is promising for the diagnosis and evaluation of coronary artery disease.

Aged↗

Relative contribution of renal nerve and adrenal gland to renal vascular tone during prolonged canine hemorrhagic hypotension.

This study was designed to determine roles of renal sympathetic nerve activity (RNA) and adrenal catecholamines in the changes of renal vascular resistance during prolonged hemorrhagic shock in anesthetized dogs. In animals with intact baroreceptors, hemorrhagic hypotension (40 mm Hg) caused RNA to increase significantly within 1 min after bleeding, followed by a return to baseline within 10 min. Thereafter, a secondary increase in RNA occurred that was followed by a gradual decline towards the baseline level. The renal perfusion pressure (RPP) showed a progressive and significant increase until the end of the experiment. The initial increase in RNA was abolished by complete denervation of the systemic baroreceptors. The initial increase in RPP, which was observed within 10 min after bleeding in animals with intact baroreceptors, was attenuated by the denervation. In animals with bilateral adrenalectomy, RPP still showed an initial increase, but the progressive increase throughout the entire experimental period did not occur. In animals with baroreceptor denervation and bilateral adrenalectomy, RPP did not show any significant changes during the experiment. These results indicate that the initial renal vasoconstrictive response to hemorrhage is regulated by a reflex sympathetic mechanism. In contrast, a late renal vasoconstriction during hemorrhagic hypotension is predominantly evoked by humoral substances such as adrenal catecholamines.

Adrenal Glands↗

Differential control of sympathetic outflow to kidney, heart, adrenal gland, and liver during systemic hypotension induced by cardiac tamponade in anesthetized dogs.

This study was designed to determine if cardiac tamponade-induced hypotension produces differential control in efferent sympathetic nerve activity to the kidney (RNA), heart (CNA), adrenal gland (AdNA), and liver (HNA) in pentobarbital-anesthetized dogs and to define whether systemic baroreceptors modify this response. We recorded RNA, CNA, AdNA, and HNA simultaneously during a 10 min period of sustained hypotension of 50 mm Hg, which was produced by intrapericardial saline infusion at 20 ml/min. When blood pressure reached 50 mm Hg, sympathetic nerve activity to all four organs increased significantly. Following this, RNA decreased significantly below the control (72 +/- 12%) at the end of experiment, while CNA, AdNA, and HNA remained elevated above control values throughout the experiment. Renal sympathoinhibition was reversed by cervical vagotomy, whereas this had no effect on CNA, AdNA, and HNA responses to hypotension. Additionally, the combined denervation of vagal, carotid sinus, and aortic nerves did not show any significant change in any variables. Thus these results indicate that hypotension due to cardiac tamponade in dogs produces an initial equivocal sympathoexcitation to the kidney, heart, adrenal gland, and liver followed by vagal afferent-mediated sympathoinhibition to the kidney but sustained excitation to the other three organs.

Adrenal Glands↗

Organ distribution and characterization of porcine peptides (VIP, CGRP and PHI) that increase cAMP in rat platelets.

Using an assay for rat platelet cAMP, we investigated the organ distribution of peptides that increase cAMP in rat platelets in porcine tissues. Marked activity was observed in the duodenum, pancreas and brain. By analysis with reverse phase high performance liquid chromatography (HPLC), three major peaks of activity were observed in porcine tissues. The first peak was vasoactive intestinal polypeptide (VIP), and the second peak was calcitonin gene-related peptide (CGRP). The third peak of activity was isolated from porcine duodenum. By analysis with a gas phase sequencer and with an amino acid analyzer, this peptide was identified as peptide histidine isoleucine (PHI). In a glucagon-secretin family of neuropeptides, pituitary adenylate cyclase activating polypeptide (PACAP) significantly increased platelet cAMP levels in a dose-dependent manner; however, glucagon did not. These results suggest that not only VIP and CGRP but also PHI and PACAP act upon platelets, as well as vascular tissues.

Amino Acid Sequence↗

Isolation and characterization of peptides which act on rat platelets, from a pheochromocytoma.

An increase in the cellular concentration of cAMP leads to the inhibition of platelet aggregation. We have been investigating endogenous peptides which inhibit platelet function, using an assay which detects increase in platelet cAMP. Compared with the human adrenal medulla, a pheochromocytoma (PC) contained abundant peptides that elevate platelet cAMP. About 90% of the activity was found in the SP-III fraction which contained strongly basic peptides. From the SP-III fraction, peptides P-1, P-2 and P-3 were purified to homogeneity as endogenous peptides which elevated platelet cAMP. A gas phase sequencer was used to identify these peptides as follows: P-1 = vasoactive intestinal peptide (VIP); P-2 = calcitonin gene related peptide-I (CGRP-I); P-3 = CGRP-II. It is well known these peptides are potent vasorelaxants. VIP and CGRP-I significantly increased platelet cAMP levels 15- and 6-fold, respectively. These results suggest that VIP and CGRP-I and -II act upon platelets as well as upon vascular tissue.

Adrenal Gland Neoplasms↗

Difference in the concentration of tryptophan metabolites between maternal and umbilical foetal blood.

Maternal and umbilical foetal blood at delivery were analysed for tryptophan metabolites by using fully automated high-performance liquid chromatography. The metabolites detected in 100 microliters of maternal plasma were kynurenine, serotonin, 5-hydroxyindoleacetic acid, indolelactic acid, indoleacetic acid and indolepropionic acid. These metabolites were present in various amounts in the protein-bound form. Except for indolepropionic acid, the concentrations of tryptophan metabolites were significantly higher in umbilical foetal plasma than in maternal plasma. In addition, 3-hydroxyanthranilic acid was present in umbilical foetal blood, but not in maternal blood. Furthermore, kynurenic acid was also detected in amniotic fluids.

Amino Acids↗

Myocardial oxidative metabolism in normal subjects in fasting, glucose loading and dobutamine infusion states.

Experimental studies indicated the clearance rate constant of 11C-acetate as an index of regional myocardial oxygen consumption. To assess the response of the clearance rate from the left ventricular (LV) myocardium to the change in plasma substrate levels and to the increase in the cardiac work load in normal subjects, a total of 18 dynamic positron emission tomographic studies were performed at rest in the fasting state (control) (n = 7), after oral glucose administration (n = 4), and during dobutamine infusion (n = 7) in 7 normal volunteers. The clearance rate constant (Kmono) was similar in the control (0.065 +/- 0.017 min-1) and glucose loading states (0.059 +/- 0.008 min-1), whereas a significant increase in Kmono was observed during dobutamine infusion (0.106 +/- 0.018 min-1) (p < 0.01) in relation to the increase in the pressure-rate product with a correlation coefficient of 0.873 (p < 0.01). When the LV myocardium was divided into 6 segments, there were no significant differences among the segments in Kmono values in any condition. These normal responses should be valuable for assessing oxidative metabolic reserve and regional changes in oxidative metabolism in patients with coronary artery disease.

Adult↗

Spatial and temporal differing control of sympathetic activities during hemorrhage.

We performed simultaneous multifiber recordings of cardiac, renal (RNA), hepatic (HNA), adrenal, and splenic sympathetic nerve activities during 10 min of sustained hemorrhagic hypotension to a mean blood pressure of 50 mmHg. One minute after bleeding in dogs with intact baroreceptors, all measured nerve activities increased significantly, and a gradual decline toward prebleeding level followed. Only RNA showed a great inhibition below prebleeding level. In cervically vagotomized dogs, all nerve activities showed significantly higher levels than prebleeding control throughout the experiment. The initial increase in HNA observed at 1 min postbleeding in animals with intact baroreceptors was attenuated. HNA in the vagotomized group showed a gradual increase so that 5 min postbleeding, HNA reached a peak level that was maintained until the end of the experiment. Sympathoinhibition in RNA and decrease in heart rate during hemorrhagic hypotension were reversed to significant increases after vagotomy. In contrast, animals with denervation of the carotid sinus and aortic nerves showed initial increases in nerve activities followed by recovery to prebleeding control level within 2 min postbleeding. After complete denervation of systemic baroreceptors, rapid hemorrhage did not cause any significant change in sympathetic nerve activity in any nerve. These results indicate that early reflex response to hemorrhage in regional sympathetic nerves is unidirectional sympathoexcitation mediated by summative unloading of both arterial baroreceptors and cardiopulmonary receptors. When greater than 1 min passed after bleeding and sustained hypotension of 50 mmHg was established, a reflex mechanism through the vagal afferents participated to inhibit the unidirectional sympathoexcitation mediated by unloading of arterial baroreceptors, with different magnitude in different innervated organs.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Glands↗