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Biomedical subjects

M Fukuyama

Publications and source records attributed to M Fukuyama.

At least 55 records · Page 3Linked to original sources

[Studies on hemolytic streptococcal infection: 1). Outbreak of group C hemolytic streptococcal infection in Formosan squirrels].

Between mid-October to mid-November 1992, of 500 freely-ranging Formosan and striped squirrels kept at Garden Y in the suburbs of Kanagawa Prefecture, 414 (82.8%) suddenly died one after another by bleeding from the nasal and oral cavities after developing a mild facial swelling. Isolation of microbes including viruses were carried out from the Formosan squirrels that had suddenly died. Various organs from these animals were histologically examined. 1. In bacteriological tests, beta-hemolytic streptococcal strains were isolated in a pure culture from 5 (83.3%) of 6 Formosan squirrels that had died suddenly. By serological analysis, 14 isolated strains were serotyped as group C according to the classification of Lancefield. From their biochemical characteristics, these were identified as Streptococcus equi subsp. zooepidemicus. A drug sensitivity test revealed that ABPC, PCG, SBPC, CMX and CPZ are highly sensitive against the isolates. 2. In the virological test, the viral isolation was applied for three blind passages by primary cultured kidney cells of Formosan squirrels, but no evidence of CPE was obtained. 3. At autopsy, a pathological change was detected mainly in the lungs. Histopathological examinations revealed severe hypertrophic changes of the alveolar wall in the entire pulmonary lobe. Severe congestion, hemorrhagic pneumonia, neutrophils and macrophages infiltration were observed in the hypertrophic alveolar wall. In the other cases, thrombi were observed in the branches of the pulmonary artery. Other organs demonstrated no remarkable histopathological changes. 4. Streptococcal strains were not isolated from the pharynx in all of the employees working at this garden.

Animals↗

Low shear stress can initiate von Willebrand factor-dependent platelet aggregation in patients with type IIB and platelet-type von Willebrand disease.

Platelets exposed to shear stress aggregate in the absence of exogenously added agonists, utilizing distinct platelet membrane receptors and ligands depending upon the level of shear stress applied. Using a modified cone and plate type viscometer, we previously demonstrated that, under low shear stress (18 dyn/cm2), aggregation is mediated by platelet membrane glycoprotein (GP) IIb-IIIa and fibrinogen, whereas aggregation induced by high shear stress (108 dyn/cm2) requires the binding of von Willebrand factor (vWF) to both GPIb-IX and GPIIb-IIIa (Ikeda, Y., M. Handa, K. Kawano, T. Kamata, M. Murata, Y. Araki, H. Anbo, Y. Kawai, K. Watanabe, I. Itagaki, et al. 1991. J. Clin. Invest. 87:1234-1240). Here we report that vWF-dependent aggregation occurs under low shear stress in citrated platelet-rich plasma (PRP) from two types of congenital bleeding disorders, platelet-type von Willebrand disease (vWD) and type IIB vWD, in both of which ristocetin-induced aggregation is known to be heightened. Aggregation induced by low shear stress was enhanced in both types of disorders compared to normal controls, and the enhancement was completely abolished by anti-vWF monoclonal antibody NMC-4, which blocks the GPIb-binding site on vWF. Under high shear stress, the extent of maximal aggregation was not different between controls and the patient groups although maximal aggregation was reached much more quickly in the latter. When citrated PRP was exposed to a gradient of shear stress (6 to 108 dyn/cm2 over a 5-min period), vWF-dependent aggregation, as judged from the inhibitory effect of NMC-4, first occurred at 14 dyn/cm2 in platelet-type vWD and at 10-12 dyn/cm2 in type IIB vWD, as compared with more than 81 +/- 20.1 dyn/cm2 in control platelets. These results suggest that an abnormality in either vWF or GPIb-IX triggers the aggregation-inducing interaction of the two molecules under low shear stress, which might explain the intravascular platelet clumping, that presumably underlies the thrombocytopenia observed in these bleeding disorders.

Humans↗

[Studies on motile-Aeromonas infection 3). Phage typing of motile Aeromonas isolated from patients with diarrhea].

Phage types were determined for 102 strains of motile Aeromonas isolated from patients with diarrhea at four metropolitan hospitals in Tokyo. The following results were obtained. 1) Of the 102 strains examined, 52 (51.0%) were divided into 28 phage types. This rate was considerably higher, compared to our previous results, namely, 21.7% for strains isolated from natural environments and 25% for those isolated from meats. By bacterial species, phage types could be determined for 33 (52.4%) of 63 strains of A. hydrophila, for 16 (45.7%) of 35 strains of A. sobria, 2 (50.0%) of 4 strains of A. caviae and 1 (100%) strain of Aeromonas spp. 2) Of the 52 strains for which the phage types could be determined, the greatest number (16 strains, 30.8%) were identified as belonging to Type I group. These are followed by 5 strains (9.6%) which were identified as Type I/III group and 2 strains (3.4%) each identified as Type I/II, I/II/V, IV, V and VI groups. The remaining 21 strains were identified as belonging to one of the other phage type groups. Thirty-five (67.3%) of the strains for which the phage types were identified, were found to belong either to Type I group or to combinations with Type I. This demonstrated that 34.0% of the isolates from patients with diarrhea were related to Type I.

Aeromonas↗

Epinephrine augments von Willebrand factor-dependent shear-induced platelet aggregation.

BACKGROUND: Shear-induced platelet aggregation (SIPA) is an important mechanism in thrombogenesis. von Willebrand factor (vWF) binding to platelet glycoprotein Ib (GP Ib) has been found to be crucial for platelet aggregation under the high shear force probably generated in stenosed coronary artery. The physiological significance of vWF-dependent SIPA has not been clarified. METHODS AND RESULTS: Blood samples were collected from 23 normal volunteers. SIPA was continuously monitored using a modified cone-plate viscometer adapted for measuring the transmitted light intensity of the material. The effects of low concentrations of epinephrine, ADP, and collagen on SIPA under both low shear (12 dyne/cm2) and high shear (108 dyne/cm2) force were investigated. All agonists tested enhanced SIPA under low shear force, whereas only epinephrine augmented SIPA under high shear force. The maximum extents of SIPA under high shear force in the absence and presence of epinephrine (10 ng/ml) were 37.9 +/- 11.5% and 59.7 +/- 13.9%, respectively. The antagonist of the alpha 2-adrenergic receptor yohimbine (1 microgram/ml) antagonized the effects of epinephrine. The monoclonal antibody NMC-4 against vWF, which was shown to inhibit its binding to GP Ib, completely abolished SIPA under high shear force, even in the presence of epinephrine. However, this antibody only partially inhibited SIPA under low shear force. CONCLUSIONS: Our findings suggest that epinephrine is the agonist that enhances SIPA mediated by vWF through its specific receptor. This may be clinically important because occlusion of the coronary artery often occurs in stenosed atherosclerotic vessels under sympathetic stimulation.

Adrenergic alpha-Antagonists↗

[Studies on motile-Aeromonas infection: 2). Development of a bacteriophage typing system for motile Aeromonas].

We succeeded in isolating Aeromonas-susceptible phages from river water and mud after a few years (1983-1985) of painstaking effort. For the first time in Japan, we investigated phagetypes of the bacterial strains isolated. The results obtained are summarized as follows: 1) Aeromonas-susceptible phages were isolated from 82 (40.1%) of 195 samples of river water and from 23 (25.6%) of 90 samples of river mud. By the cross-matching test of the phages isolated from the 105 samples, these were classified into 13 type groups (Groups I-XIII). 2) When 594 Aeromonas strains isolated from river water, lake water, river mud and fresh-water fish were examined using the phage group patterns developed by us, 129 (21.7%) strains classified into these phagetypes. Phagetyping was possible for 11 (15.5%) of the 71 strains isolated from river and lake water, for 29 (35.4%) of the 82 strains from river mud and for 89 (20.2%) of the 441 strains from fresh-water fish. By bacterial species, phagetyping was possible for 53 (51.5%) of the 103 strains of A. hydrophila. 21 (7.2%) of the 292 strains of A. sobria, 13 (8.8%) of the 148 strains of A. caviae and 42 (82.4%) of the 51 strains of Aeromonas spp.. Especially the phages classified as Groups I, IV and VI amounted to the majority. Thus we succeeded in isolating Aeromonas-susceptible phages which could be classified into Groups I-XIII. The results suggested the possibility of utilizing this phagetyping for analysis of the ecological distribution of genus Aeromonas.

Aeromonas↗

Continuous measurement of shear-induced platelet aggregation.

A mechanical device for continuous recording of shear-induced platelet aggregation (SIPA) has been developed using a turbidometric technique. The device consists of three components: light source, a thermostated cone-plate streaming chamber and optical detection unit. There was a good correlation between platelet count and transmitted light intensity under the conditions in which no activation of platelets occurred. When platelets were exposed to shear stress at 37 degrees C, transmitted light intensity increased with time. Scanning electronmicroscopic examinations revealed that more prominent platelet aggregation was demonstrated when light intensity increased. Reproducible recording of SIPA was obtained when experiments were repeated using the same sample. No change in light intensity was observed when formalin-fixed platelets were sheared. Both PGE1, and anti-GPIIb/IIIa mouse monoclonal antibody, AP2, showed complete inhibition of SIPA. It is indicated that our device for continuous measurement of SIPA is an important new tool to study one aspect of platelet functions.

Formaldehyde↗

[Studies on motile-Aeromonas infection: incidence of motile-Aeromonas in river mud, river water and fresh-water fish].

During the period from October 1982 to July 1984, a total of 1,157 specimens that consisted of 132 river and lake water, 514 river and lake muds, and 511 fresh-water fish caught in both Tama River and Sagami River were examined the presence of the organisms. Of them, 132 (100%) river and lake waters, 304 (59.1%) river and lake muds, and 462 (90.4%) intestinal contents of fresh-water fish were found to have harbor a mean concentration of 1.3 x 10(3)/l, 1.6 x 10(6)/g, and 1.1 x 10(6)/g of motile-Aeromonas respectively. However, nonseasonal variation was observed in the incidence of the organisms throughout the period of investigation. When attempts were made to classify the isolates by the method described Popoff et al., 17 (14.2%) of 120 water-isolates were typed as A. hydrophila, 33 (27.5%) as A. sobria and 35 (29.2%) as A. caviae respectively. And the rest of the 35 (29.2%) remained untypable. As for the 176 mud-isolates, 38 (21.6%) were typed as A. hydrophila 23 (13.1%) as A. sobria and 41 (23.3%) as A. caviae respectively. And the rest of 74 (42.0%) remained untypable. Some efforts were made on the 1,056 strains obtained from fresh-water fish, and 182 (17.2%) were typed as A. hydrophila, 332 (31.4%) as A. sobria and 206 (19.5%) as A. caviae respectively. And the rest of the 336 (31.8%) remained untypable.

Aeromonas↗

Interaction of noradrenaline and dopamine in patients with essential hypertension or with pheochromocytoma.

To analyse the interaction of noradrenaline (NA) and dopamine (DA) release, the present study compared urinary outputs of total NA and DA as well as plasma levels of total NA and DA in normotensive (NT) subjects, in patients with essential hypertension (EHT) and in a patient with pheochromocytoma. Significant correlations between total NA and DA in urine were observed in NT subjects, in patients with EHT and in a patient with pheochromocytoma. A significant correlation was observed in plasma total NA and DA of blood collected from several veins except for the tumor vein, by indwelling catheter, in a patient with pheochromocytoma. These results suggest that DA is released from sympathetic nerve terminals in response to an augmented release of NA.

Adrenal Gland Neoplasms↗

Comparison of nisoldipine and atenolol in the treatment of essential hypertension.

The antihypertensive effects of nisoldipine, a calcium channel blocker, and atenolol, a beta-adrenergic blocker, were compared in patients with mild or moderate essential hypertension. Both drugs produced significant reductions in blood pressure from the 8th week through the end of the 12-week treatment period. The hear rate decreased significantly in the atenolol group but not in the nisoldipine group. Following oral administration of 50 mg of captopril, the rise in plasma renin activity was significantly smaller in both treatment groups than in normotensive controls. The magnitude of the pressor response during a hand-grip test tended to be smaller in both groups of patients than in the controls, with no significant difference between the treated groups. Although the plasma catecholamine concentration rose significantly in the control and nisoldipine groups, there were no significant intergroup differences in these parameters. The hemoglobin, GOT, creatinine, total cholesterol and serum sodium and potassium concentrations all decreased significantly in the nisoldipine group, although the values remained within normal limits. These results indicate that both nisoldipine and atenolol significantly suppress both plasma renin activity and the pressor response to stress leading to reduction of blood pressure.

Adult↗

Salt increases blood pressure with biphasic changes in hypothalamic responsiveness in rats.

Tail-cuff systolic pressures became elevated in male Wistar rats fed chow containing 8% NaCl for 4 weeks. After 4 weeks of salt loading, pressor and sympathetic responses to ventromedial hypothalamic stimulation were larger in salt-loaded rats. When similar experiments were done following sinoaortic denervation, all of the effects previously induced by dietary salt loading persisted. By contrast, after only 1 week of salt loading, pressor and sympathetic responses to hypothalamic stimulation were reduced, instead of being increased. Since circulating plasma volume was increased in week 1, it was considered possible that reduced hypothalamic responsiveness was due to enhanced cardiopulmonary baroreflexes. Supporting this interpretation, bilateral vagotomy reversed the hypothalamic inhibition occurring in week 1. Although neither the site nor mechanism causing sympathetic hyperactivity has been determined, our results indicate that chronic dietary salt loading has biphasic effects on the ventromedial hypothalamus: an initial inhibition in the first week followed by stimulation thereafter. These results could mean that dietary salt loading eventually increases sympathetic activity and thereby induces hypertension by stimulating the ventromedial hypothalamus.

Animals↗

Hypotension and hypothalamic depression produced by intracerebroventricular injections of GABA in spontaneously hypertensive rats.

To determine the central effects of 4-Amino-n-butyric acid (GABA), pressor and sympathetic nerve responses to electrical stimulation of the ventromedial hypothalamus were recorded following the intracerebroventricular (ICV) injection of GABA. In normotensive Wistar rats, anesthetized with urethane, ICV injections of GABA (50-200 micrograms) reduced sympathetic nerve activity, arterial blood pressure, and heart rate in a dose-dependent manner. Graded electrical stimulation of the ventromedial hypothalamus (50, 100, 150 microA) increased not only mean blood pressure but also the rate of sympathetic nerve firing, and both responses were attenuated by GABA pretreatment (100, 200 micrograms, ICV). In spontaneously hypertensive rats (SHR), ICV-injected GABA also reduced sympathetic and cardiovascular activity, but the magnitude of depressor responses was significantly larger in SHR than in normotensive Wister Kyoto controls (WKY). Pressor and sympathetic nerve responses elicited by ventromedial hypothalamic stimulation were initially larger in SHR than in WKY, but upon subsequent ICV injection of GABA, hypothalamic responsiveness in SHR was inhibited more prominently and became comparable to that in WKY. These results suggest that by depressing hypothalamic function, centrally injected GABA decreases sympathetic nerve activity to thereby lower blood pressure and heart rate, and in SHR, ICV-injected GABA reversed hypothalamo-sympathetic hyperactivity and thus attenuated hypertension.

Animals↗

Enhanced renal sympathetic nerve activity in response to salt loading in rats.

To analyze the conflicting data on the relationship between sodium intake and sympathetic activity, the effects of a chronically excessive intake of sodium on renal sympathetic activity and blood pressure were investigated in normotensive rats. Renal sympathetic activity was estimated by urinary excretion of free norepinephrine (NE) and the turnover of NE in the kidneys. Blood pressure increased in rats receiving a high sodium diet when compared with that of the basal sodium diet. Urinary-free NE, epinephrine (E) and dopamine (DA) excretions in rats receiving a high sodium diet were enhanced significantly from those in the basal sodium diet. The turnover of NE in the kidneys was more enhanced in the high sodium group than in the basal sodium group. By blocking the sympathetic tone with ganglionic blockade, hexamethonium, enhanced excretion of urinary NE and elevation of blood pressure in response to salt loading were blocked to the levels of the basal sodium diet. These results suggest that a chronically excessive intake of sodium enhances the renal sympathetic and adreno-medullary activities, leading to a rise in blood pressure in normotensive rats.

Animals↗