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Biomedical subjects

M Yoshimura

Publications and source records attributed to M Yoshimura.

At least 55 records · Page 3Linked to original sources

Assessment of platelet cytosolic concentration of free magnesium in healthy subjects.

We measured basal cytosolic concentration of free Mg2+ ([Mg2+]i) in platelets from 30 healthy volunteers by using mag-fura-2, a new fluorescent Mg2+ indicator. The mean [Mg2+]i was 381 +/- 22 mumol/L, with values ranging from 226 to 771 mumol/L. The day-to-day intrasubject coefficient of variation was relatively small (3.6%). [Mg2+]i was significantly higher in men than in women (430 +/- 38 vs 332 +/- 17 mumol/L, p < 0.03), and was not correlated with age. There was no significant relation between platelet [Mg2+]i and serum total Mg concentration. The results indicate that the gender but not age may decide intracellular Mg2+ status. In addition, the mechanisms that regulate [Mg2+]i may be independent of those that influence the extracellular concentration of Mg.

Adult

Prior mechanical injury inhibits rise in intracellular Ca2+ concentration by oxygen-glucose deprivation in mouse hippocampal slices.

Prior mechanical brain microinjury has been found to have a preventive effect on brain ischemia. To investigate the mechanism responsible for this, the effect of mechanical brain injury on changes in intracellular free Ca2+ concentration ([Ca2+]i) in response to ischemic insult was studied in mouse hippocampal slices. The mechanical injury was made by inserting a 25G hypodermic needle into the CA1 region of the hippocampus in mice anesthetized with pentobarbital. Sagittal slices of the hippocampus were prepared two hours, and 1, 3, 7, and 14 days after the brain injury. Changes in [Ca2+]i in the slices by oxygen-glucose deprivation were analyzed from fluorescence images, using fura-2. Increases in [Ca2+]i induced by oxygen-glucose deprivation were inhibited in the vicinity of the injury 1 and 3 days after injury. [Ca2+]i levels were lower in the posterior side from the injury than in the anterior side 1 and 3 days after injury. No significant regional differences in [Ca2+]i responses were found 2 h or 7 and 14 days after the injury. Membrane potential and membrane resistance of CA1 neurons in the vicinity of the injury measured 1 day after the injury were not significantly altered in comparison with non-injured slices. These results indicate that mechanical brain injury inhibits ischemic [Ca2+]i increase. This inhibition may be induced not only by damage of the presynaptic fibers projecting to the CA1 neurons but also by the other certain factor(s) that prevent [Ca2+]i increase, and it appears to be related to the protective effect of prior mechanical injury against ischemic neuronal damage.

Animals

Synaptic responses of substantia gelatinosa neurones to dorsal column stimulation in rat spinal cord in vitro.

1. To study the mechanism of dorsal column stimulation-induced depression of nociceptive transmission in the spinal cord, synaptic responses evoked in dorsal horn neurones by dorsal column and dorsal root stimulations were examined in a horizontal spinal cord slice of the adult rat. Intracellular recordings were made from substantia gelatinosa (SG) neurones. 2. All SG neurones examined received monosynaptic inputs and/or polysynpatic inputs from both dorsal column and dorsal root. A delta fibres were probably responsible for the synaptic responses. The responses evoked by dorsal column stimulation were similar to those evoked by primary afferent A delta fibre stimulation. 3. Monosynaptic excitatory postsynaptic potentials (EPSPs) evoked by dorsal column A delta fibres were depressed by 6-cyano-7-nitroquinoxaline-2,3-dione, suggesting that these fibres released L-glutamate or a related amino acid as a transmitter. 4. In 38 of 101 SG neurones, dorsal column stimulation evoked an initial EPSP followed by fast and/or slow inhibitory postsynaptic potentials (IPSPs). These IPSPs reversed polarity at a membrane potential of -73 +/- 2 mV. The fast IPSPs observed in 16 of the SG neurones (42%) that received inhibitory inputs were depressed by strychnine, while the slow IPSPs observed in 22 SG neurones were depressed by bicuculline. In a few cells, a long-lasting slow IPSP with a much slower time course was detected; this IPSP was insensitive to strychnine and bicuculline, and reversed polarity at a membrane potential near -90 mV. 5. Repetitive stimulation of the dorsal column depressed the amplitude of monosynaptic EPSPs evoked by dorsal root stimulation. 6. The responses of SG neurones to dorsal column stimulation had configurations and durations similar to responses to dorsal root stimulation, and may be mediated largely by the same A delta fibres. However, a C fibre-mediated response could not be detected in SG neurones from dorsal column stimulation, although dorsal root stimulation could evoke C fibre-mediated monosynaptic EPSPs in 18 of 88 SG neurones (20%). 7. These observations suggest that SG neurones receive abundant A delta but not C fibre inputs from the dorsal column and that dorsal column stimulation inhibits primary afferent transmission in the spinal cord both by reducing transmitter release from primary A delta fibres and by hyperpolarizing SG neurones.

2-Amino-5-phosphonovalerate

Assessment of urinary beta-core fragment of human chorionic gonadotropin as a new tumor marker of lung cancer.

BACKGROUND: Some patients with lung cancer have been found to have elevated levels of serum immunoreactive human chorionic gonadotropin (hCG)/hCG beta (IR-beta), but it is uncertain whether it would be valuable as a tumor marker. Recently, IR-beta has been demonstrated to consist of at least three different molecules, intact hCG, free hCG beta, and hCG beta-core fragment (beta-CF), in body fluids. In this study, the authors qualitatively analyzed IR-beta in the serum and urine of patients with lung cancer and assessed its clinical usefulness as a tumor marker. METHODS: Highly sensitive and specific enzyme immunoassays were established to measure intact hCG, free hCG beta, and beta-CF in the serum and urine of patients with lung cancer. RESULTS: Of 99 patients with lung cancer, almost half of the patients achieved positive values of IR-beta in the urine, although only 12 had elevated values of IR-beta in the serum. The greater part of the elevated urinary IR-beta was identified to be beta-CF by gel chromatography on Sephadex G-100 (Pharmacia LKB Biotechnology, Tokyo, Japan), leading the authors to assess its usefulness as a tumor marker for lung cancer. Based on the cutoff value (0.2 ng/mg of creatinine) from healthy subjects, the overall positive rate of urinary beta-CF for lung cancer was 48.5% (48 of 99 patients). The incidence of the marker increased with stage of disease, from 35.7% (15 of 42) in Stage I and 35.7% (5 of 14) in Stage II to 62.5% (20 of 32) in Stage III and 72.7% (8 of 11) in Stage IV. These positive rates exceeded or equaled those of the serum tumor markers, carcinoembryonic antigen, and squamous cell carcinoma (SCC)-related antigen, measured simultaneously in the same patients. The author were encouraged that there was no significant difference in the positive rates of urinary beta-CF between two major types of lung cancer: adenocarcinoma (49.2%) and SCC (45.2%). Immunohistochemical study revealed positive staining of IR-beta in the cancer tissues from 5 of 12 patients with elevated levels of IR-beta, in which most of the positive cases had the elevated levels of serum free hCG beta (> 0.5 ng/ml) and/or urinary beta-CF (> 1.0 ng/mg of creatinine). CONCLUSIONS: Ectopic production of IR-beta by lung cancer is not rare, and urinary beta-CF might be a potential tumor marker of lung cancer.

Adenocarcinoma

Capacitative Ca2+ entry regulates Ca(2+)-sensitive adenylyl cyclases.

A number of the currently described adenylyl cyclase species can be regulated by Ca2+ in the submicromolar concentration range in in vitro assays. The regulatory significance of these observations hinges on whether a physiological elevation in intracellular Ca2+ can regulate these cyclase activities in intact cells. However, achieving a physiological elevation in cytosolic Ca2+ is complicated by the fact that hormonal increases in cytosolic Ca2+ can be accompanied by additional effects, such as liberation of beta gamma-subunits of G-proteins and activation of protein kinase C, which can have disparate type-specific effects on cyclase activities. Therefore we have devised a strategy based on capacitative Ca2+ entry to show that, when types I and VI adenylyl cyclase are expressed in human embryonic kidney 293 cells, they are stimulated and inhibited respectively by Ca2+ entry. Blockade of Ca2+ entry by La3+ ions blocks the effects of Ca2+ entry on cyclic AMP synthesis. These studies establish that adenylyl cyclases deemed to be sensitive to Ca2+ in in vitro assays can be regulated by physiological Ca2+ entry, and therefore, such cyclases are poised to respond to changes in intracellular Ca2+ in tissues in which they are expressed.

Adenylyl Cyclases

Treatment of tuberculous empyema with multiple fistulae by reexpansion of the affected lung and restoration of its function: report of a case.

We report herein the case of a patient in whom a calcified tuberculous empyema with multiple fistulae was successfully treated by a new surgical approach. Reexpansion of the affected lung which had calcified over 30 years was achieved by covering the multiple bronchial fistulae using the omentum without obliterating the empyema cavity. Although the patient presented with severe aspiration pneumonia, he made a complete recovery and is now leading a better quality of life than before. This new operative method is less invasive and can therefore be performed much more easily on critically ill patients than conventional methods.

Bronchial Fistula

One hundred and one cases of bronchoplasty for primary lung cancer.

The results of 101 consecutive bronchoplasties performed between 1979 and 1993, including 8 cases of pneumonectomy, 88 cases of lobectomy, 3 cases of segmentectomy, and 2 cases of bronchial resection, are herein reported. Squamous cell carcinoma was the most common disease (59%) followed by adenocarcinoma (30%) and other diseases (11%). Anastomosis was satisfactory in 96 cases. Among the five stenosed cases, local recurrence was found in two cases, and there were three benign strictures. Two of the three benign strictures were treated with bouginage. The pulmonary artery was concomitantly reconstructed in seven cases with satisfactory results. Preoperative chemoradiotherapy was performed in 15 advanced cases and was followed by acceptable surgical results. The 5-year survival rate, according to the postoperative staging of the 86 patients without induction therapy, was 86% in stage I (19 patients), 49% in stage II (21 patients), and 27% in stage IIIA (40 patients). The overall survival rate was 46% at 5 years. There were two indications for this procedure i.e., a positive resection margin in 59 cases and positive hilar nodes in 42 cases. Better survival was noted in patients with squamous cell carcinoma, stage I, and surgery was thus selected for a positive resection margin, and not for a positive node.

Bronchi

Successful surgical treatment of a pseudoaneurysm after composite graft replacement of the aortic valve and ascending aorta: report of two cases.

Composite graft replacement of the ascending aorta and aortic valve has now become a safe surgical procedure; however, early and late complications still frequently occur. Anastomotic dehiscence after a composite graft replacement is one potentially lethal complication. We herein report two cases of a pseudoaneurysm caused by dehiscence of the right coronary anastomosis, and the proximal aortic anastomosis. A follow-up with an echocardiogram and computed tomography scan was found to be very useful and accurate. We thus successfully treated two cases of pseudoaneurysm using either Bentall's or Carbrol's procedures.

Adult

The superiority of exercise testing over spirometry in the evaluation of postoperative lung function for patients with pulmonary disease.

Thoracic surgeons have often been embarrassed by the discrepancy between an improvement in symptoms and the unchanged or even worse results of spirometry in postoperative patients with either bullae or inflammatory lung disease. Forty-four patients with lung diseases, who underwent a total of 47 operations, were categorized as follows: 12 cases of empyema, 16 cases of giant bulla (undergoing surgery a total of 19 times), 4 cases of bronchiectasis, and 12 cases of other miscellaneous diseases. All patients were tested preoperatively and again 4-6 months after surgery on both the spirometer and treadmill exercise tests. The forced vital capacity (FVC) and forced expiratory volume (FEV1.0) results were as follows: the empyema group 1.82 +/- 0.52 liters preoperatively to 1.93 +/- 0.69 liters postoperatively and 1.47 +/- 0.44 liters to 1.56 +/- 0.53 liters, respectively; and the giant bulla group, 3.49 +/- 0.96 liters to 3.35 +/- 0.77 liters and 2.35 +/- 0.96 liters to 2.48 +/- 0.69 liters, respectively. However, the exercise time was prolonged in the empyema group from 6.00 +/- 3.77 min to 8.33 +/- 3.80 min (P < 0.01) and in the giant bulla group from 11.83 +/- 3.71 min to 12.92 +/- 2.84 min (P < 0.05). It was thus concluded that exercise testing should be chosen for the postoperative evaluation of patients with inflammatory pulmonary disease and giant bullae, especially if any discrepancies are seen between spirometry and performance status, because on the basis of our results, it appears that the benefits obtained by surgery are best measured by the dynamic values of exercise testing and not by the static values of spirometry at rest.

Adult

Value of thallium-201 early reinjection for assessment of myocardial viability.

To assess the efficacy of early reinjection for predicting post intervention improvement in thallium-201 (T1) uptake and regional wall motion, we reinjected a small dose of T1 following post-stress imaging and obtained reinjection early images (10 min after early reinjection) and reinjection delayed images (3 hr afterwards) in 40 patients who were referred to us for revascularization (group I). Twenty-nine patients in group I also underwent conventional stress-redistribution T1 scintigraphy (group II). Conventional stress-redistribution T1 scintigraphy was repeated after intervention. Contrast left ventriculography was performed before and after intervention and changes in regional wall motion were assessed in 22 of 40 patients. In group I, the predictive value for improvement and no improvement (the accuracy) of reinjection early images in perfusion was 83%, while that of reinjection delayed images was 91%. Furthermore, the accuracy of reinjection early images in regional wall motion was 80%, while it was 91% for reinjection delayed images. In group II, the accuracy in perfusion was 78% and the value in regional wall motion was 70%. Both accuracy in perfusion and in regional wall motion obtained from reinjection delayed images were significantly higher than the values in group II (p < 0.05). These data suggest that early reinjection is useful for predicting postintervention thallium uptake and regional wall motion.

Aged

A clinical feature of myocardial stunning associated with acute myocardial infarction.

We report a case of myocardial stunning after acute myocardial infarction. In the hyperacute phase of myocardial infarction, the patient's coronary arteries showed normal features on coronary angiography during extensive ST-segment elevation observed on a standard 12-lead electrocardiogram and extensive akinesis observed on a left ventriculogram. Thallium-201 emission computed tomography revealed extensive perfusion abnormality. In the chronic phase, the perfusion abnormality was markedly improved. However, the electrocardiogram demonstrated poor R wave progression, and the left ventriculography revealed slight hypokinesis in the anterolateral wall. The acetylcholine provocation test disclosed coronary vasospasm of the left anterior descending coronary artery. About six months thereafter, left ventricular wall motion became completely normal and no poor R wave progression was observed on the electrocardiogram. The findings in this case indicate that myocardial stunning resulted from brief but sever ischemia due to vasospasm which led to cardiogenic shock, and that the recovery of findings for thallium-201 perfusion might be followed by those of electrocardiography and left ventriculography in the stunned myocardium.

Acetylcholine

Suppression of hyperventilation-induced attacks with infusion of B-type (brain) natriuretic peptide in patients with variant angina.

B-type (brain) natriuretic peptide (BNP) forms a peptide family with A-type (atrial) natriuretic peptide (ANP), which is involved in the regulation of blood pressure and fluid volume. We have demonstrated that BNP is a novel cardiac hormone secreted predominantly from the ventricle and that plasma levels of BNP markedly increase in proportion to the severity of congestive heart failure. Spasm of a major coronary artery (coronary spasm) is the cause of variant angina and can be induced by hyperventilation. We examined whether BNP infusion suppresses coronary spasm in patients with variant angina. The effect of BNP infusion on anginal attacks induced by hyperventilation was studied in 11 patients with variant angina in whom the attacks were reproducibly induced by hyperventilation. This study was performed in the early morning on 3 consecutive days. Fourteen minutes after infusion of BNP was begun (day 2, 0.05 micrograms/kg/min) or saline (days 1 and 3), hyperventilation was started and continued for 6 minutes. Anginal attacks were induced in all 11 patients by hyperventilation on days 1 and 3, respectively. Anginal attacks were not induced in any patient on day 2 (BNP infusion). Fourteen minutes after BNP infusion was begun, plasma BNP levels increased from 23.7 +/- 6.7 pg/ml to peak levels of 2591 +/- 255 pg/ml (p < 0.01) and plasma ANP levels increased from 28.9 +/- 7.5 pg/ml to peak levels of 69.2 +/- 13.2 pg/ml. Five minutes after BNP infusion was finished, plasma levels of cyclic guanosine monophosphate (cGMP) increased from 20.3 +/- 7.4 pg/ml to peak levels of 63.5 +/- 13.7 pg/ml (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Reduced cardiac extraction of norepinephrine and epinephrine in patients with heart failure--correlation with left ventricular function.

To assess whether the impairment of neuronal norepinephrine (NE) uptake is involved in the increased NE release observed in the failing heart, we examined the cardiac extractions of NE and epinephrine (E) and their correlation with left ventricular function in 16 patients with anterior transmural old myocardial infarction (OMI) and 18 patients with dilated cardiomyopathy (DCM). The plasma NE and E levels were both increased in OMI and DCM, particularly in the coronary sinus, as compared with those in 16 control subjects (Control). The cardiac NE and E extractions were significantly reduced in OMI (P < 0.001) and in DCM (P < 0.001) as compared with those in the Control (NE: -38 +/- 36% in OMI, -33 +/- 28% in DCM, and 14 +/- 18% in Control; E: 30 +/- 12% in OMI, 32 +/- 17% in DCM, and 54 +/- 8% in Control). However, there was no reduction in the NE and E extraction in the leg in OMI and DCM. Cardiac NE and E extractions both showed significant correlation with the left ventricular ejection fraction (r = 0.685, P < 0.001 and r = 0.609, P < 0.001, respectively). We conclude that, in patients with heart failure, NE release from the heart is increased partially due to the reduction of the cardiac neuronal uptake of NE which is proportional to the severity of left ventricular dysfunction.

Aged

Infantile progressive spinal muscular atrophy with ophthalmoplegia and pyramidal symptoms.

Two siblings presented with identical features of progressive peripheral paralysis of the lower motor neuron type, pyramidal signs, cranial nerve palsy which included external ocular palsy and deafness, and internal ocular palsy; both died before 1 year of age. Pathologic examination of the central nervous system in both patients revealed degeneration and loss of spinal and cranial nerve motor nuclei, including the oculomotor nucleus. In addition, there was degeneration of the Edinger-Westphal nuclei and demyelination of the corticospinal tract under the midbrain. Although spinal cord lesions were indistinguishable from those of Werdnig-Hoffmann disease, the 2 patients are not considered to have Werdnig-Hoffmann disease from the clinicopathologic findings.

Brain

Centrally induced vasopressor and sympathetic responses to a novel endogenous peptide, adrenomedullin, in anesthetized rats.

Possible central actions of adrenomedullin were explored and compared with the peripheral effects by injecting it into the lateral ventricle, cisterna magna, and femoral vein in urethane-anesthetized rats. Adrenomedullin, 1.0 to 3.0 nmol/kg, injected intravenously (i.v.), caused a transient vasodepression of about 10 to 30 mm Hg, dose dependently, which lasted for < 15 min. On the other hand, intracerebroventricular (ICV) and intracisternal (IC) injections of adrenomedullin elicited sustained elevations of arterial pressure of gradual onset, dose dependently; the arterial pressure started to rise at about 3 min after the injection, and gained peak response after > 20 min. The pressor response lasted for > 2 h. Heart rate was not significantly influenced by these doses of adrenomedullin. The abdominal sympathetic outflow was markedly increased in relation to the blood pressure elevation. The time-course of the responses was quite similar with both ICV and IC injections. Hypotensive effects of i.v. injected adrenomedullin was partially attenuated, and the centrally induced vasopressor responses were abolished by the pretreatment with human calcitonin gene-related peptide (hCGRP)-receptor antagonist, hCGRP(8-37). These findings indicate that the receptors for adrenomedullin exist in the brain, and that the receptor site may be anatomically far from the surface of the brain and the ventricular system because the onset of the pressor response was delayed. Or, CGRP and adrenomedullin may share the same receptors, particularly in the brain.

Adrenomedullin

Modulation of sodium current by lactate in guinea pig ventricular myocytes.

OBJECTIVE: The aim was to elucidate whether or not lactate modifies the fast sodium current (INa) in cardiac cells. METHODS: A tight seal whole cell clamp technique was used to record the action potentials and INa in single ventricular cells from the guinea pig heart. RESULTS: In voltage clamp experiments, superfusion with 20 mM lactate shifted both the normalised conductance (gNa)-voltage relationship and the channel availability curve toward hyperpolarisation by approximately 4 mV, but did not affect the maximum conductance (gNa,max). In the test solution containing only CaCl2 as the main divalent component, 20 mM lactate reduced the ionised calcium concentration from 1.02 to 0.84 mM. When the calcium concentration was kept constant by the addition of CaCl2 into the lactate containing solution the lactate effect was nullified. However, a change in the calcium concentration from 1.0 to 0.84 mM without lactate induced a 4 mV negative shift of the channel availability curve. Current clamp experiments in Tyrode solution showed that 20 mM lactate shifted the threshold for the action potential upstroke by 2.5-3 mV, in accordance with the voltage clamp experiments. CONCLUSIONS: Lactate modifies INa of ventricular myocytes by shifting its kinetics toward hyperpolarisation. This shift seems to be caused exclusively by a decrease in the ionised divalent cation concentrations and a resultant change in the negative surface charge of the sarcolemma.

Action Potentials