Biomedical subjects

M Yoshimura

Publications and source records attributed to M Yoshimura.

At least 91 records · Page 5Linked to original sources

PubMed2000

Expression of T-cell-associated antigens in B-cell non-Hodgkin's lymphoma.

We performed the immunophenotyping of 101 patients with B-cell non-Hodgkin's lymphoma (B-NHL) using two-colour flow cytometry (FCM) and found that lymphoma cells coexpressed at least one kind of T-cell-associated antigen (T-Ag; CD2, CD5, CD7) in 25 patients (24. 8%). Among these three T-Ags, CD5 was the most frequently expressed, in 21 patients (20.8%), followed by CD7, expressed in five patients (5.0%), and CD2, which was expressed in two patients (2.0%). Two kinds of T-Ag were simultaneusly expressed in three patients (CD2/CD5, CD2/CD7, and CD5/CD7, each expressed in one patient). Concerning the expression pattern of T-Ag, there were no significant differences between lymph nodes and extranodal organs in the three patients with T-Ag-positive B-NHL (T-Ag(+) B-NHL) who were analysed. When comparing the clinical features between T-Ag(+) B-NHL and T-Ag-negative B-NHL (T-Ag(-) B-NHL), extranodal involvement and higher International Prognostic Index (H and H.I.) were significantly frequent in the former subgroup (P = 0.0119 and P = 0. 0302 respectively).

Adolescent↗

PubMed2000

Ginkgo biloba extract attenuates the development of hypertension in deoxycorticosterone acetate-salt hypertensive rats.

1. We examined the effects of Ginkgo biloba extract (GBE) on the development of hypertension, platelet activation and renal dysfunction in deoxycorticosterone acetate (DOCA)-salt hypertensive rats. Both DOCA-salt hypertensive rats and normotensive rats were fed a 2% GBE diet for 20 days. Blood pressure (BP) was measured by two methods, namely by the tail-cuff and telemetry methods. 2. Development of hypertension was attenuated in rats fed a 2% GBE diet. In addition, an increase in heart weight, an indicator of sustained high BP, was inhibited significantly by feeding of the GBE diet. 3. Decreases in 5-hydroxytryptamine content in platelets, a marker of platelet activation in vivo associated with hypertension, were also prevented by feeding of the GBE diet. Ginkgo biloba extract itself did not inhibit ADP- and collagen-induced platelet aggregation examined in vitro. Feeding of the GBE diet tended to inhibit increases in plasma urea nitrogen due to hypertension. 4. The telemetry study demonstrated that BP and heart rate (HR) showed a clear circadian rhythm and the antihypertensive effect of GBE was prominent in the daytime, a resting period for rats. This anti-hypertensive effect of GBE was not detected in normotensive rats. In contrast, the inhibitory effect of GBE on HR was independent of time and was observed in both normotensive and hypertensive rats. 5. These results indicate that GBE has an anti-hypertensive and bradycardiac action, which are time dependent and independent, respectively. Thus, it appears that the chronopharmacological action of GBE may be ascribed not to pharmacokinetic factors, but rather to a circadian susceptibility rhythm to GBE in DOCA-salt hypertensive rats.

Animals↗

PubMed2000

Eicosapentaenoic acid stimulates nitric oxide production and decreases cardiac noradrenaline in diabetic rats.

1. The aim of the present study was to investigate whether long-term oral administration of eicosapentaenoic acid increases nitric oxide (NO) production and affects cardiac sympathetic activity in rats with diabetes mellitus. 2. We measured changes in urinary excretion of NO3-, a stable NO metabolite, and cardiac noradrenaline (NA) concentrations in non-diabetic rats and streptozotocin-induced diabetic rats treated with either ethyl icosapentate (EPA-E; 100 mg/kg per day; n = 10), a purified ethyl esterification product of eicosapentaenoic acid, or vehicle (distilled water; n = 10) for 6 weeks. The effects of N(G)-nitro-L-arginine (L-NNA), a NO synthase inhibitor, on urinary NO3- excretion and cardiac NA concentrations were also investigated in diabetic rats treated with EPA-E. 3. Urinary NO3- excretion was higher at weeks 5 and 6 in diabetic rats treated with EPA-E than in diabetic rats treated with vehicle (week 5: 120+/-8 vs 51+/-11 micromol/g per day, respectively (P<0.01); week 6: 279+/-83 vs 73+/-9 micromol/g per day, respectively (P<0.01)). Cardiac NA concentrations were higher in diabetic rats than in non-diabetic rats and were decreased in the left atrium and both ventricles in diabetic rats treated with EPA-E compared with control. Systemic administration of L-NNA abolished the increase in urinary excretion of NO3- and the decrease in cardiac NA concentrations in diabetic rats treated with EPA-E. 4. Long-term oral administration of EPA-E may stimulate NO production and increased NO is likely to play a role in inhibiting enhanced cardiac sympathetic activity in diabetic rats.

Animals↗

PubMed2000

Up-regulation of monocyte chemoattractant protein-1 in tubulointerstitial lesions of human diabetic nephropathy.

BACKGROUND: We previously described that monocyte chemoattractant protein-1 (MCP-1) plays an important role in progressive glomerular and interstitial damage in inflammatory renal diseases. However, the expression of MCP-1 in diabetic nephropathy remains to be investigated. METHODS: We examined whether locally expressed MCP-1 participates in human diabetic nephropathy via recruiting and activating monocytes/macrophages (Mphi). Urinary and serum MCP-1 levels were measured by enzyme-linked immunosorbent assay in 45 patients with diabetic nephropathy. The presence of MCP-1 in diseased kidneys was determined by immunohistochemical and in situ hybridization analyses. RESULTS: Urinary MCP-1 levels were significantly elevated in patients with diabetic nephrotic syndrome and advanced tubulointerstitial lesions. Moreover, urinary levels of MCP-1 were well correlated with the number of CD68-positive infiltrating cells in the interstitium. In contrast, serum MCP-1 levels remained similar to those of healthy volunteers. Furthermore, we detected the MCP-1-positive cells in the interstitium of diabetic nephropathy via both immunohistochemical and in situ hybridization analyses. CONCLUSION: These observations suggest that locally produced MCP-1 may be involved in the development of advanced diabetic nephropathy, especially in the formation of tubulointerstitial lesions possibly through Mphi recruitment and activation. Moreover, up-regulation of MCP-1 may be a common pathway involved in the progressive tubulointerstitial damage in diabetic nephropathy as well as inflammatory renal diseases.

Adolescent↗

PubMed2000

Interaction on metabolic clearance between A-type and B-type natriuretic peptides in patients with heart failure.

A-type and B-type natriuretic peptides (ANP and BNP) are secreted into the systemic circulation via the coronary sinus. Plasma levels of ANP and BNP at the coronary sinus should directly determine the systemic circulating levels. However, the metabolic clearance of these hormones are dependent on similar systems, natriuretic peptide clearance receptor (NPR-C) and neutral endopeptidase 24.11 (NEP), suggesting a possible interaction between ANP and BNP on metabolic clearance. In this study, we examined the interaction on metabolic clearance in patients with heart failure. We obtained blood samples from the coronary sinus and aortic root in 100 patients with heart failure and 28 control subjects. The difference in ANP and BNP levels between the coronary sinus and the aortic root is reflected partly by the metabolic clearance in the pulmonary circulation. In this study, we examined the possible interaction on metabolic clearance between ANP and BNP using a statistical procedure. The ratio of the level of BNP to ANP (BNP/ANP) was significantly higher in the aortic root than in the coronary sinus at any stage of heart failure. We performed multiple regression analysis using ANP and BNP levels at the coronary sinus as independent variables (X1 and X2, respectively) and the ANP level at the aortic root as a dependent variable (Y). The analysis showed that both X1 and X2 were significant variables in the equation. On the other hand, we performed the same analysis using the BNP level at the aortic root as a dependent variable (Y). The analysis showed that only X2 was a significant variable in the equation. This study suggests that (1) the metabolic clearance in the pulmonary circulation is higher for ANP versus BNP and (2) the amount of ANP cleared in the pulmonary circulation depends on the amount of both ANP and BNP secreted from the heart, whereas the amount of BNP cleared in the pulmonary circulation is dependent solely on the amount of BNP secreted from the heart.

Aorta↗

PubMed2000

A case of Høyeraal-Hreidarsson syndrome: delayed myelination and hypoplasia of corpus callosum are other important signs.

We report the case of a 7-year old girl with Høyeraal-Hreidarsson syndrome (HHS) and review other cases of HHS. In addition to the previously described important signs of HHS, i.e., prenatal growth retardation, microcephaly, psychomotor retardation, progressive pancytopenia, immunological abnormalities, and cerebellar hypoplasia and ataxia, we consider that delayed myelination of cerebral white matter and hypoplastic corpus callosum should be added to the list of important signs. However, it is not clear whether delayed myelination of white matter in HHS indicates dysmyelination or demyelination. Furthermore, we suggest that immunological abnormalities of both T and B cells are one of the important signs of HHS. We consider these new important signs to be valuable for the diagnosis of HHS.

Agenesis of Corpus Callosum↗

PubMed2000

Norepinephrine facilitates inhibitory transmission in substantia gelatinosa of adult rat spinal cord (part 1): effects on axon terminals of GABAergic and glycinergic neurons.

BACKGROUND: The activation of descending norepinephrine-containing fibers from the brain stem inhibits nociceptive transmission at the spinal level. How these descending noradrenergic pathways exert the analgesic effect is not understood fully. Membrane hyperpolarization of substantia gelatinosa (Rexed lamina II) neurons by the activation of alpha2 receptors may account for depression of pain transmission. In addition, it is possible that norepinephrine affects transmitter release in the substantia gelatinosa. METHODS: Adult male Sprague-Dawley rats (9-10 weeks of age, 250-300 g) were used in this study. Transverse spinal cord slices were cut from the isolated lumbar cord. The blind whole-cell patch-clamp technique was used to record from neurons. The effects of norepinephrine on the frequency and amplitude of miniature excitatory and inhibitory postsynaptic currents were evaluated. RESULTS: In the majority of substantia gelatinosa neurons tested, norepinephrine (10-100 microM) dose-dependently increased the frequency of gamma-aminobutyric acid (GABA)ergic and glycinergic miniature inhibitory postsynaptic currents; miniature excitatory postsynaptic currents were unaffected. This augmentation was mimicked by an alpha1-receptor agonist, phenylephrine (10-60 microM), and inhibited by alpha1-receptor antagonists prazosin (0.5 microM) and 2-(2,6-dimethoxyphenoxyethyl) amino-methyl-1,4-benzodioxane (0.5 microM). Neither postsynaptic responsiveness to exogenously applied GABA and glycine nor the kinetics of GABAergic and glycinergic inhibitory postsynaptic currents were affected by norepinephrine. CONCLUSION: These results suggest that norepinephrine enhances inhibitory synaptic transmission in the substantia gelatinosa through activation of presynaptic alpha1 receptors, thus providing a mechanism underlying the clinical use of alpha1 agonists with local anesthetics in spinal anesthesia.

Adrenergic alpha-Agonists↗

PubMed2000

Norepinephrine facilitates inhibitory transmission in substantia gelatinosa of adult rat spinal cord (part 2): effects on somatodendritic sites of GABAergic neurons.

BACKGROUND: It has been reported previously that norepinephrine, when applied to the spinal cord dorsal horn, excites a subpopulation of dorsal horn neurons, presumably inhibitory interneurons. In the current study, the authors tested whether norepinephrine could activate inhibitory interneurons, specifically those that are "GABAergic." METHODS: A transverse slice was obtained from a segment of the lumbar spinal cord isolated from adult male Sprague-Dawley rats. Whole-cell patch-clamp recordings were made from substantia gelatinosa neurons using the blind patch-clamp technique. The effects of norepinephrine on spontaneous GABAergic inhibitory postsynaptic currents were studied. RESULTS: In the majority of substantia gelatinosa neurons tested, norepinephrine (10-60 microM) significantly increased both the frequency and the amplitude of GABAergic inhibitory postsynaptic currents. These increases were blocked by tetrodotoxin (1 microM). The effects of norepinephrine were mimicked by the alpha1-receptor agonist phenylephrine (10-80 microM) and inhibited by the alpha1-receptor-antagonist WB-4101 (0.5 microM). Primary-afferent-evoked polysynaptic excitatory postsynaptic potentials or excitatory postsynaptic currents in wide-dynamic-range neurons of the deep dorsal horn were also attenuated by phenylephrine (40 microM). CONCLUSION: The observations suggest that GABAergic interneurons possess somatodendritic alpha1 receptors, and activation of these receptors excites inhibitory interneurons. The alpha1 actions reported herein may contribute to the analgesic action of intrathecally administered phenylephrine.

Adrenergic alpha-1 Receptor Agonists↗

PubMed2000

Actions of midazolam on GABAergic transmission in substantia gelatinosa neurons of adult rat spinal cord slices.

BACKGROUND: Although intrathecal administration of midazolam has been found to produce analgesia, how midazolam exerts this effect is not understood fully at the neuronal level in the spinal cord. METHODS: The effects of midazolam on either electrically evoked or spontaneous inhibitory transmission and on a response to exogenous gamma-aminobutyric acid (GABA), a GABA(A)-receptor agonist, muscimol, or glycine were evaluated in substantia gelatinosa neurons of adult rat spinal cord slices by using the whole-cell patch-clamp technique. RESULTS: Bath-applied midazolam (1 microM) prolonged the decay phase of evoked and miniature inhibitory postsynaptic currents (IPSCs), mediated by GABA(A) receptors, without a change in amplitudes, while not affecting glycine receptor-mediated miniature inhibitory postsynaptic currents in both the decay phase and the amplitude. Either GABA- or muscimol-induced currents were enhanced in amplitude by midazolam (0.1 microM) in a manner sensitive to a benzodiazepine receptor antagonist, flumazenil (1 microM); glycine currents were, however, unaltered by midazolam. CONCLUSIONS: Midazolam augmented both the duration of GABA-mediated synaptic current and the amplitude of GABA-induced current by acting on the GABA(A)-benzodiazepine receptor in substantia gelatinosa neurons; this would increase the inhibitory GABAergic transmission. This may be a possible mechanism for antinociception by midazolam.

2-Amino-5-phosphonovalerate↗

PubMed2000

Overexpression of type 7 adenylyl cyclase in the mouse brain enhances acute and chronic actions of morphine.

The mechanisms by which morphine-induced analgesia and tolerance and physical dependence on morphine arise have been the subject of intense study, and much work has pointed to the involvement of cAMP-mediated events in the neuroadaptive phenomena leading to morphine tolerance and/or dependence. We overexpressed an opioid receptor-stimulatable form of adenylyl cyclase (type 7) in the central nervous system of mice and demonstrated significant effects of this manipulation on the animals' acute response to morphine, the development of morphine tolerance, and development of sensitization to morphine. Measurements of the acute analgesic response to morphine demonstrated that the ED(50) values for the transgenic mice were significantly lower than the ED(50) values determined for the "wild-type" animals. During chronic treatment with morphine, the transgenic mice developed tolerance more rapidly than the wild-type mice, and transgenic animals of the C57BL/6xSJL background showed a larger sensitization to morphine's effects on locomotor activity than did wild-type mice of the same background. These results indicated that cAMP-generating systems may simultaneously modulate the development of tolerance and sensitization. Interestingly, the signs of physical dependence on morphine in the transgenic mice did not differ from those in their wild-type litter mates, indicating that separate mechanisms may modulate opiate tolerance and opiate dependence.

Adenylyl Cyclases↗

PubMed2000

Formation of methyl mercaptan from L-methionine by Porphyromonas gingivalis.

Methyl mercaptan production by oral bacteria is thought to be one of the main causes of oral malodor. We examined the ability of periodontopathic Porphyromonas gingivalis to produce methyl mercaptan from L-methionine and found that the invasive strains W83 and W50 produced large amounts of methyl mercaptan. We cloned and sequenced the mgl gene encoding L-methionine-alpha-deamino-gamma-mercaptomethane-lyase (METase) from P. gingivalis W83. The structural mgl gene consisted of 1,200 bp and encoded a 43.3-kDa protein. To examine the role of methyl mercaptan in the pathogenesis of P. gingivalis, a METase-deficient mutant of P. gingivalis W83 was constructed. The methionine degradation activity and virulence of the mutant (M1217) and the parent strain (W83) in mice were compared. M1217 showed a marked decrease in the formation of methyl mercaptan from L-methionine and decreased virulence compared with the wild-type strain W83. These results suggest that methyl mercaptan not only is one of the sources of oral malodor, but may also play a role in the pathogenicity of P. gingivalis.

Animals↗

PubMed2000

In vivo patch-clamp analysis of IPSCs evoked in rat substantia gelatinosa neurons by cutaneous mechanical stimulation.

To know a functional role of inhibitory synaptic responses in transmitting noxious and innoxious information from the periphery to the rat spinal dorsal horn, we examined inhibitory postsynaptic currents (IPSCs) elicited in substantia gelatinosa (SG) neurons by mechanical stimuli applied to the skin using the newly developed in vivo patch-clamp technique. In the majority (80%) of SG neurons examined, a brush stimulus applied to the ipsilateral hind limb produced a barrage of IPSCs that persisted during the stimulus, while a pinch stimulus evoked IPSCs only at its beginning and end. The pinch-evoked IPSCs may have been caused by a touch that occurs at the on/off time of the pinch. The evoked IPSCs were blocked by either a glycine-receptor antagonist, strychnine (4 microM), or a GABA(A)-receptor antagonist, bicuculline (20 microM). All SG neurons examined received inhibitory inputs from a wide area throughout the thigh and lower leg. When IPSCs were examined together with excitatory postsynaptic currents (EPSCs) in the same neurons, a brush evoked a persistent activity of both IPSCs and EPSCs during the stimulus while a pinch evoked such an activity of EPSCs but not IPSCs. It is suggested that innoxious mechanical stimuli activate a GABAergic or glycinergic circuitry in the spinal dorsal horn. This inhibitory transmission may play an important role in the modulation of noxious information in the SG.

Animals↗

PubMed2000

Increased blood vascular endothelial growth factor levels in patients with acute myocardial infarction.

Vascular endothelial growth factor (VEGF) is a growth factor for vascular endothelial cells in vitro. The present study was designed to determine whether serum VEGF levels increase in patients with acute myocardial infarction (AMI) compared with patients with stable exertional angina and control subjects, and to examine the serial changes of serum VEGF levels in patients with AMI. We examined serum VEGF levels by using antibody prepared from serum immunized with human VEGF(121). The serum VEGF level (pg/ml) was higher (p < 0. 0001) on admission in the patients with AMI (177 +/- 19) than in those with stable exertional angina (61 +/- 7) and control subjects (62 +/- 6). The serum VEGF level (pg/ml) of the patients with AMI was 177 +/- 19 on admission, 125 +/- 9 on day 3, 137 +/- 11 on day 5, 242 +/- 18 at 1 week, and 258 +/- 22 at 2 weeks after admission. The value was higher on admission than on day 3 after admission (p = 0.014), the values were higher at 1 week and 2 weeks than on admission, on day 3, and 5 (p < 0.01). Furthermore, there were correlations between peak VEGF levels at 1 week or 2 weeks after admission and peak creatine kinase levels. The increase of VEGF on admission in the patients with AMI may be due to the hypoxia of acute myocardial ischemia. The elevation at 1 week and 2 weeks from the onset may cause the development of collateral circulation in relation to the healing of the infarction site.

Aged↗

PubMed2000

Hemodynamic and hormonal effects of the angiotensin II antagonist, candesartan cilexetil, in patients with congestive heart failure.

Candesartan cilexetil is a newly synthesized, specific angiotensin II type 1 receptor antagonist. Candesartan cilexetil is a prodrug, and is converted to its active form, candesartan, by the enzyme esterase at the time of intestinal absorption. We conducted a single-dose study to evaluate the effect of candesartan cilexetil on cardiac hemodynamics and hormone response in 13 patients with congestive heart failure. Mean blood pressure did not show any significant change in the patients receiving either 2 or 8 mg. Pulmonary capillary wedge pressure was reduced by 34.9% in the patients given 8 mg of candesartan cilexetil. The cardiac index did not show any significant changes. Total peripheral vascular resistance was reduced in the patients receiving 2 or 8 mg from 1 h after administration, and the tendency to decrease continued until 8 h after administration. Plasma atrial natriuretic peptide levels were reduced by 15.5% 2 h after dosing with 8 mg of candesartan cilexetil. Plasma brain natriuretic peptide levels decreased slightly after dosing with candesartan cilexetil. Administration of candesartan cilexetil reduces cardiac preload and afterload and is expected to be useful for the treatment of congestive heart failure.

Administration, Oral↗

PubMed2000

Role of FMRFamide-activated brain sodium channel in salt-sensitive hypertension.

FMRFamide, a cardioexcitatory neuropeptide, directly activates a newly cloned amiloride-sensitive sodium channel that is expressed specifically in the brain and blocked by benzamil hydrochloride. In the present study, we investigated the effects of short- and long-term intracerebroventricular infusion of FMRFamide on arterial pressure, sympathetic activity, vasopressin release, and brain renin-angiotensin system genes in rats and studied the role of FMRFamide-activated brain sodium channels in salt-sensitive hypertension. The intracerebroventricular preinjection of FMRFamide and subsequent intracerebroventricular infusion of 0.15 mol/L NaCl increased mean arterial pressure (FMRFamide: 30 nmol/kg +13+/-2.6 mm Hg, P<0.01; 100 nmol/kg +21+/-1.8 mm Hg, P<0.01), heart rate, abdominal sympathetic activity, and plasma vasopressin concentration compared with vehicle. The intracerebroventricular copreinjection with either benzamil or CV-11974 abolished these increases. In rats administered a high-salt diet (8% NaCl), the continuous intracerebroventricular infusion of FMRFamide (50 and 200 nmol. kg(-1). d(-1)) for 5 days increased mean arterial pressure, heart rate, urinary excretion of vasopressin and norepinephrine, and mRNAs of renin, angiotensin I-converting enzyme, and angiotensin II type 1 receptor in hypothalamus and brain stem compared with vehicle. These increases were abolished by intracerebroventricular coinfusion of benzamil. In rats administered a low-salt diet (0.3% NaCl), however, increases in these variables were smaller than those in rats receiving a high-salt diet. Together, these findings suggest that brain FMRFamide-activated sodium channels may be involved in the mechanism of salt-sensitive hypertension through regulation of the brain renin-angiotensin system.

Amiloride↗

PubMed2000

The plasma levels of dehydroepiandrosterone sulfate are decreased in patients with chronic heart failure in proportion to the severity.

Dehydroepiandrosterone sulfate (DHEAS) is the major secretory steroid of the human adrenal glands. The secretion of DHEAS decreases with aging. The incidence of heart failure also rises in the elderly population. We measured the plasma levels of DHEAS and cortisol in 49 patients with chronic heart failure (CHF) and 32 age-matched controls and assessed its relation to plasma levels of A-type natriuretic peptide and B-type natriuretic peptide, biochemical markers of heart failure. Plasma levels of DHEAS were significantly lower in patients with CHF than in controls, whereas there was no significant difference in plasma levels of cortisol between the two groups. In stepwise regression analysis, the plasma level of DHEAS was significantly and independently correlated with age (beta = -0.451; P < 0.0001) and the plasma level of B-type natriuretic peptide (beta = -0.338; P < 0.001), and the plasma cortisol/DHEAS ratio was significantly and independently correlated with the plasma levels of A-type natriuretic peptide (beta = 0.598; P < 0.0001) and thiobarbituric acid-reactive substances (a marker of oxidative stress; beta = 0.252; P < 0.01) and age (beta = 0.171; P < 0.05). These results indicate that the plasma levels of DHEAS are decreased in patients with CHF in proportion to its severity and that oxidative stress is associated with decreased levels of DHEAS in patients with CHF.

Adult↗

PubMed2000

Calcium regulation of microtubule sliding in reactivated sea urchin sperm flagella.

The changes in the bending pattern of flagella induced by an increased intracellular Ca(2+) concentration are caused by changes in the pattern and velocity of microtubule sliding. However, the mechanism by which Ca(2+) regulates microtubule sliding in flagella has been unclear. To elucidate it, we studied the effects of Ca(2+) on microtubule sliding in reactivated sea urchin sperm flagella that were beating under imposed head vibration. We found that the maximum microtubule sliding velocity obtainable by imposed vibration, which was about 170-180 rad/second in the presence of 250 microM MgATP and <10(-9) M Ca(2+), was decreased by 10(-6)-10(-5) M Ca(2+) by about 15-20%. Similar decrease of the sliding velocity was observed at 54 and 27 microM MgATP. The Ca(2+)-induced decrease of the sliding velocity was due mainly to a decrease in the reverse bend angle. When the plane of beat was artificially rotated by rotating the plane of vibration of the pipette that held the sperm head, the asymmetric bending pattern also rotated at 10(-5) M Ca(2+) as well as at <10(-9) M Ca(2+). The rotation of the bending pattern was observed at MgATP higher than 54 microM ( approximately 100 microM ATP). These results indicate that the Ca(2+)-induced decrease of the sliding velocity is mediated by a rotatable component or components (probably the central pair) at high MgATP, but is not due to specific dynein arms on particular doublets. We further investigated the effects of a mild trypsin treatment and of trifluoperazine on the Ca(2+)-induced decrease in sliding velocity. Axonemes treated for 3 minutes with a low concentration (0.1 microgram/ml) of trypsin beat with a more symmetrical waveform than before the treatment. Also, their microtubule sliding velocity and reverse bend angle were not affected by high Ca(2+) concentrations. Trifluoperazine (25-50 microM) had no effect on the decrease of the sliding velocity in beating flagella at 10(-5) M Ca(2+). However, the flagella that had been 'quiescent' at 10(-4) M Ca(2+) resumed asymmetrical beating following an application of 10-50 microM trifluoperazine. In such beating flagella, both the sliding velocity and the reverse bend angle were close to their respective values at 10(-5) M Ca(2+). Trypsin treatment induced a similar recovery of beating in quiescent flagella at 10(-)(4) M Ca(2+), albeit with a more symmetrical waveform. These results provide first evidence that, at least at ATP concentrations higher than approximately 100 microM, 10(-6)-10(-5) M Ca(2+) decreases the maximum sliding velocity of microtubules in beating flagella through a trypsin-sensitive regulatory mechanism which possibly involves the central pair apparatus. They also suggest that calmodulin may be associated with the mechanism underlying flagellar quiescence induced by 10(-4) M Ca(2+).

Animals↗

PubMed2000

Elevated levels of soluble intercellular adhesion molecule-1 in the coronary circulation of patients with coronary organic stenosis and spasm.

The cell surface expression of intercellular adhesion molecule-1 (ICAM-1) is upregulated following activation during inflammatory responses, mediating both cell migration and activation. The involvement of inflammation in unstable angina is suggested by the presence of activated circulating leukocytes. To examine whether plasma soluble ICAM-1 (sICAM-1) levels increase in the coronary circulation of patients with coronary organic stenosis and coronary spasm, plasma sICAM-1 levels were measured in the coronary sinus (CS) and the aortic root (Ao) simultaneously in 10 patients with 90% or more coronary narrowing and coronary spasm (coronary spastic angina (CSA) with organic stenosis), in 11 patients with coronary spasm and no significant coronary narrowing (CSA without organic stenosis), in 16 patients with stable exertional angina, and in 13 control subjects. The plasma sICAM-1 levels (ng/ml) in the CS increased in CSA with organic stenosis (230+/-26) as compared with CSA without organic stenosis (158+/-14), stable exertional angina (130+/-9) and control subjects (121+/-10) (p<0.01). The levels in the Ao also increased in CSA with organic stenosis (208+/-24) as compared with CSA without organic stenosis (149+/-13), stable exertional angina (130+/-11) and control subjects (121+/-10) (p<0.01). Furthermore, the plasma sICAM-1 levels were higher in the CS than in the Ao only in CSA with organic stenosis. These results suggest that activation of leukocytes occurs through the induction of ICAM-1 in the coronary circulation in the patients with CSA with organic stenosis.

Aged↗